Penicillin

Biochemistry, 2005 Jan 25, 44(3), 1078 - 87
Direct Evidence That the Reaction Intermediate of Metallo-beta-lactamase L1 Is Metal Bound; Garrity JD et al.; In an effort to probe the structure of the reaction intermediate of metallo-beta-lactamase L1 when reacted with nitrocefin and other beta-lactams, time-dependent absorption and rapid-freeze-quench (RFQ) EPR spectra were obtained using the Co(II)-substituted form of the enzyme . When using nitrocefin as the substrate, time-dependent absorption spectra demonstrate that Co(II)-substituted L1 utilizes a reaction mechanism, similar to that of the native Zn(II) enzyme, in which a short-lived intermediate forms . RFQ-EPR spectra of this intermediate demonstrate that the binding of substrate results in a change in the electronic properties of one or both of the Co(II)'s in the enzyme that is consistent with a change in the coordination sphere of this metal ion . This observation provides evidence that the reaction intermediate is a metal-bound species . RFQ-EPR studies also demonstrate that other beta-lactams, such as cephalothin, meropenem, and penicillin G, proceed through an electronically similar complex and that the role of metal is similar in all cases . EPR spectroscopy has also identified distinct product-bound species of L1, indicating that reversible product binding must be considered in all future kinetic mechanisms . Consideration of the time-dependent optical and EPR studies in light of available crystallographic information indicates the intimate involvement of the metal ion in the Zn(2)-binding site of L1 in the hydrolytic reaction.

J Biotechnol, 2005 Mar 2, 116(1), 1 - 10 Epub 2004 Nov 21.
Improved stabilization of chemically aminated enzymes via multipoint covalent attachment on glyoxyl supports; Lopez-Gallego F et al.; The surface carboxylic groups of penicillin G acylase and glutaryl acylase were chemically aminated in a controlled way by reaction with ethylenediamine via the 1-ethyl-3-(dimethylamino-propyl) carbodiimide coupling method . Then, both proteins were immobilized on glyoxyl agarose . In both cases, the immobilization of the chemically modified enzymes improved the enzyme stability compared to the stability of the immobilized but non-modified enzyme (by a four-fold factor in the case of PGA and a 20-fold factor in the case of GA) . The chemical modification presented a deleterious effect on soluble enzyme stability . Therefore, the improved stability should be related to a higher multipoint covalent attachment, involving both the lysine amino groups and also the new amino groups chemically introduced on the enzyme . Moreover, the lower pK(a) of the new amino groups permitted to immobilize the enzyme under milder conditions . In fact, the aminated proteins could be immobilized even at pH 9, while the non-modified enzymes could only be immobilized at pH over 10.

J Bacteriol, 2005 Jan, 187(2), 544 - 53
Caulobacter crescentus Requires RodA and MreB for Stalk Synthesis and Prevention of Ectopic Pole Formation; Wagner JK et al.; Caulobacter crescentus cells treated with amdinocillin, an antibiotic which specifically inhibits the cell elongation transpeptidase penicillin binding protein 2 in Escherichia coli, exhibit defects in stalk elongation and morphology, indicating that stalk synthesis may be a specialized form of cell elongation . In order to investigate this possibility further, we examined the roles of two other proteins important for cell elongation, RodA and MreB . We show that, in C . crescentus, the rodA gene is essential and that RodA depletion leads to a loss of control over stalk and cell body diameter and a stalk elongation defect . In addition, we demonstrate that MreB depletion leads to a stalk elongation defect and conclude that stalk elongation is a more constrained form of cell elongation . Our results strongly suggest that MreB by itself does not determine the diameter of the cell body or stalk . Finally, we show that cells recovering from MreB depletion exhibit a strong budding and branching cell body phenotype and possess ectopic poles, as evidenced by the presence of multiple, misplaced, and sometimes highly branched stalks at the ends of these buds and branches . This phenotype is also seen to a lesser extent in cells recovering from RodA depletion and amdinocillin treatment . We conclude that MreB, RodA, and the target(s) of amdinocillin all contribute to the maintenance of cellular polarity in C . crescentus.

Biochemistry (Mosc), 2004 Dec, 69(12), 1386 - 90
pH Stability of Penicillin Acylase from Escherichia coli; Guranda DT et al.; The inactivation kinetics of penicillin acylase from Escherichia coli have been investigated over a wide pH range at 25 and 50 degrees C . The enzyme was very stable in neutral solutions and quickly lost its catalytic activity in acidic and alkaline solutions . In all cases, the inactivation proceeded according to first order reaction kinetics . Analysis of the pH dependence of enzyme stability provides evidence that stable penicillin acylase conformation is maintained by salt bridges . Destruction of the salt bridges due to protonation/deprotonation of the amino acid residues forming these ion pairs causes inactivation by formation of the unstable "acidic" EH(4)(3+), EH(3)(2+), EH(2)(+) and "alkaline" E(-) enzyme forms . At temperatures above 35 degrees C penicillin acylase apparently undergoes a conformational change that is accompanied by destruction of one of these salt bridges and change in the catalytic properties.

Pediatr Infect Dis J, 2004 Dec, 23(12), 1125 - 9
Impact of the conjugate pneumococcal vaccine in arkansas; Schutze GE et al.; BACKGROUND: On the basis of the success of the early trials in the prevention of invasive pneumococcal disease in infants and children using a heptavalent conjugate pneumococcal vaccine, the American Academy of Pediatrics recommended in August 2000 that the vaccine be given concurrently with other childhood immunizations . METHODS: Data concerning invasive pneumococcal infections from 1998-2000 were compared with 2001-2003 to assess the impact of the heptavalent pneumococcal conjugate vaccine in Arkansas . Basic demographic data were gathered as well as history of vaccination with the pneumococcal vaccine, underlying medical conditions, site of infection and morbidity and mortality . Pneumococcal isolates were serogrouped or serotyped and penicillin susceptibilities were obtained . RESULTS: The incidence of invasive disease decreased from a high of 5.78/100,000 population to 3.02/100,000 population (P = 0.002) . Although the percentage of White patients increased from 2001-2003, the overall incidence of disease did not change . The incidence of disease among Blacks fell from 20.5/100,000 population to 4.9/100,000 population . The greatest decrease of disease occurred in children 24 months of age or younger with the incidence rate falling from 44.2/100,00 population to 8.30/100,000 population (P < 0.02) . The incidence among White children 24 months of age or younger fell from 19/100,000 population to 1.8/100,000 population, whereas that of Black children 24 months of age or younger declined from 164/100,000 to 35/100,000.From 1998 to 2000, 3.7/100 cases were from nonvaccine serogroups compared with 44/100 cases from 2001 to 2003 (P < 0.001) . In children 24 months of age or younger, the number of nonvaccine isolates increased from 1.3/100 cases to 30.5/100 cases (P < 0.001) . Overall 56 (44%) were nonsusceptible to penicillin from 1998 to 2000; that was not significantly different from 2001-2003 when 37 (46%) of 81 isolates were nonsusceptible to penicillin . CONCLUSIONS: A significant decrease of invasive pneumococcal disease has been documented in Arkansas . Of concern, however, is the increasing number of invasive isolates not included in the current vaccine.

Hautarzt . 2004 Dec 30; {Epub ahead of print}
{Basophil activation tests in the diagnosis of drug reactions.}; Erdmann SM et al.; Over the past 10 years a number of studies on basophil activation tests (BAT) have been published which focus on their use as diagnostic methods in clarifying IgE-mediated hypersensitivity reactions to various allergens including drugs . These BAT are based on flow cytometric quantification of allergen- induced CD63 or CD203 expression or measurement of sulfo leukotriene release by ELISA . In the diagnosis of penicillin allergy, the combined use of the CD63-BAT and specific IgE increases sensitivity . The role of BAT in the diagnosis of non-IgE-mediated reactions to non-steroidal anti- inflammatory drugs remains to be clarified . This article focuses on (1) the principles of BAT, (2) technical aspects, (3) clinical applications and (4) recommendations for further development.

Hautarzt . 2004 Dec 30; {Epub ahead of print}
{Bullous drug reactions.}; Hertl-Yazdi MS et al.; Bullous drug exanthems are clinically characteristic, usually severe cutaneous and mucosal drug hypersensitivity reactions . Commonly, they appear 5-14 days after onset of drug treatment . Therapy of choice is to avoid the culprit drug and systemic administration of glucocorticoids . A key element in the immune pathogenesis of bullous drug exanthems is presumably the activation of cytotoxic CD8+ T lymphocytes which recognize drug metabolites as nominal antigens . These compounds form spontaneously (e.g . penicillins) or are metabolized by cytochrome P450-dependent enzymes (sulfonamides) . The diagnosis of bullous drug exanthems is primarily based on skin tests and in vitro-techniques . Among the skin tests, prick as well as patch tests are important . Patch tests can be also applied at the former skin lesion in fixed drug eruption . In vitro techniques include analysis of drug-specific IgE (only available for anti-penicillin, anti-sulfamethoxazole) and cellular tests with the patients' lymphocytes (lymphocyte transformation test-LTT).

J Org Chem, 2005 Jan 7, 70(1), 367 - 9
A practical synthesis of nitrocefin; Lee M et al.; Nitrocefin is a key reagent for high and low throughput assays of the activities of penicillin-binding proteins (PBPs) and beta-lactamases, the former used for discovery of antibiotics and the latter for inhibitors of resistance determinants for beta-lactam antibiotics . This compound is commercially available but is prohibitively expensive because of the circuitous routes to its synthesis . We describe herein a three-step synthesis of nitrocefin that gives an overall yield of 44% . This is a practical route to the synthesis of this key reagent for drug discovery.

Ann Thorac Surg, 2005 Jan, 79(1), 153 - 61; discussion 161-2
Local gentamicin reduces sternal wound infections after cardiac surgery: a randomized controlled trial; Friberg O et al.; BACKGROUND: Sternal wound infections remain a major cause of morbidity after cardiac surgery . Vancomycin is often the only effective antibiotic available for their treatment but its use for routine prophylaxis is inadvisable for ecological reasons . Local application of gentamicin produces high antibiotic concentrations in the wound . We aimed to determine whether this treatment could have an additive effect on the incidence of sternal wound infections when combined with routine prophylaxis . METHODS: Two thousand cardiac surgery patients were randomized to routine prophylaxis with intravenous isoxazolyl-penicillin alone (control group) or to this prophylaxis combined with application of collagen-gentamicin (260 mg gentamicin) sponges within the sternotomy before wound closure . Endpoint was any sternal wound infection within 2 months postoperatively . Evaluations were double-blind and made on an intention-to-treat basis . RESULTS: Evaluation was possible in 967 and 983 patients in the control and treatment groups, respectively . The incidence of sternal wound infection was 4.3% in the treatment group and 9.0% in the control group (relative risk 0.47; 95% confidence interval 0.33-0.68; p < 0.001) . Early reoperation for bleeding was more common in the treatment group (4.0% vs 2.3%, p = 0.03) . No difference in postoperative renal function was noted . CONCLUSIONS: Local collagen-gentamicin reduced the risk for postoperative sternal wound infections . Further studies are warranted to confirm these results, particularly with regard to deep infections.

Med Mal Infect, 2004 Apr, 34(4), 171 - 6
{Epidemiology, clinical features, and evolution of Erysipelas in the Marrakech region (100 cases)}; Amal S et al.; OBJECTIVE: We aimed to determine the epidemiological and clinical profile, and to study the evolution of this disease in the Marrakech region . MATERIAL AND METHODS: We retrospectively studied all patients with a diagnosis of erysipelas admitted in the Department of Dermatology from 1990 to 2002, in the Marrakech Mohamed VI hospital . RESULTS: A total of 100 patients were included in the study, 58 male (58%) and 42 female (42%) patients, age range 9-95 years (mean age: 47 years) . The lesions were most frequently located on the lower limbs (87% of the cases), with 82 cases occurring in the legs, whereas the face was affected in 10% of the cases . Erysipelas relapsed in 12 patients (12%) . All patients had at least one risk factor: portal of entry (80 cases, with 67 cases of toe web intertrigo), obesity (10% of the cases), lymphedema (6% of the cases), diabetes (3% of the cases) . The first line treatment was intravenous penicillin G in 76 cases (76%) . Satisfactory results were observed in 78% of the cases . COMMENTS: Erysipelas is common in hospital environment . An early penicillin therapy associated to the treatment of the portal of entry leads to satisfactory results.

Hautarzt . 2004 Dec 24; {Epub ahead of print}
{Syphilis and HIV infection Besonderheiten der Diagnose, Klinik und Therapie.}; Potthoff A et al.; The incidence of syphilis has increased dramatically in Germany since 2001 . Homosexual men have been particularly afflicted . Several characteristic features should be taken into account in the diagnosis and treatment of HIV patients with concomitant syphilis . Since laboratory analyses are frequently unreliable, the experienced physician must pay special attention to the clinical picture . The stages in the clinical course of syphilis do not differ essentially between HIV-positive and HIV-negative patients . However, atypical and serious courses with rapid progression and CNS involvement are observed more frequently . Moreover, incorrect diagnoses are often reached . Treatment requires particular diligence . Penicillin is the agent of choice for all stages of syphilis in patients infected with HIV . Because the stages are often difficult to differentiate, the choice of which penicillin derivative should be administered is the subject of controversy . There is no safe alternative for patients allergic to penicillin.

Hautarzt . 2004 Dec 24; {Epub ahead of print}
{Syphilis treatment Deutsche und internationale Leitlinien-ein Vergleich.}; Schofer H; Guidelines are an important instrument for improving the quality of medical care . In 2001, the German STD Society (DSTDG) published guidelines for syphilis diagnostics and treatment . For two reasons, these guidelines had to be reviewed urgently: Firstly, there is an obvious "renaissance" of syphilis among men having sex with men, which is complicated by a frequent comorbidity with HIV infection . Secondly, the standard drug for syphilis treatment in Germany, clemizole penicillin, has no longer been available since July 2003 . In this article, the new German guidelines for syphilis treatment 2004, published by the DSTDG, are compared with other syphilis guidelines, which are valid for the European countries, i.e., the CDC, UK, Russian, and European guidelines 2002.

Sex Transm Dis, 2005 Jan, 32(1), 1 - 6
Effectiveness of Syphilis Treatment Using Azithromycin and/or Benzathine Penicillin in Rakai, Uganda; Kiddugavu MG et al.; OBJECTIVE:: The goal of this study was to assess azithromycin and/or benzathine penicillin for treatment of syphilis . METHODS:: In a population-based study, participants with serologic syphilis (TRUST with TPHA confirmation) were offered 2.4 MU benzathine penicillin intramuscularly . Intervention arm participants received 1 g presumptive oral azithromycin . We assessed cure rates with penicillin or azithromycin given alone and in combination . Cure assessed after 10 months was defined as seroreversion or a 4-fold decrease in titer . The rate ratio (RR) of cure and 95% confidence intervals (95% CIs) were estimated by log binomial regression . RESULTS:: Among 952 cases with syphilis, 18% received penicillin alone, 17% azithromycin only, and 65% dual treatment . The overall cure rate was 61% . Cure rates were lower in males compared with females (RR, 0.89; 95% CI, 0.80-0.99) and in subjects with initial titers >/=1:4 compared with </=1:2 (RR, 0.77; 95% CI, 0.69-0.86) . There was no significant differences in cure rates among HIV-positive and HIV-negative persons . With initial titers </=1:2, there were no differences in cure rates by treatment regimen . However, with initial titers >/=1:4, significantly higher cure rates were observed with azithromycin alone (adjusted RR, 1.38; 95% CI, 0.97-1.96), and with dual treatment of azithromycin and benzathine penicillin (RR, 1.38; 95% CI, 1.03-1.87) compared with penicillin alone . CONCLUSION:: Azithromycin alone or in combination with penicillin achieved higher cure rates than penicillin alone in cases with a high initial TRUST titer . In low-titer infections, the 3 drug combinations were equally effective . HIV status did not affect cure rates.

Biotechnol Lett, 2004 Oct, 26(20), 1601 - 6
Evidence for the involvement of arginyl residue at the active site of penicillin G acylase from Kluyvera citrophila; Kumar RS et al.; Penicillin G acylase (PGA) is used for the commercial production of semi-synthetic penicillins . It hydrolyses the amide bond in penicillin producing 6-aminopenicillanic acid and phenylacetate . 6-Aminopenicillanic acid, having the beta-lactam nucleus, is the parent compound for all semi-synthetic penicillins . Penicillin G acylase from Kluyvera citrophila was purified and chemically modified to identify the role of arginine in catalysis . Modification with 20 mM phenylglyoxal and 50 mM 2,3-butanedione resulted in 82% and 78% inactivation, respectively . Inactivation was prevented by protection with benzylpenicillin or phenylacetate at 50 mM . The reaction followed psuedo-first order kinetics and the inactivation kinetics (V(max), K(m), and k(cat)) of native and modified enzyme indicates the essentiality of arginyl residue in catalysis.

Heart, 2005 Jan, 91(1), 3 - 4
Pathogenesis of acute rheumatic fever and rheumatic heart disease: evasive after half a century of clinical, epidemiological, and laboratory investigation; Kaplan EL; Rheumatic fever and rheumatic heart disease continue to be a problem for medical and public health communities--the fact that penicillin has failed to eradicate this disease process is irrefutable proof of the need for more laboratory, epidemiological, and clinical research.

Di Yi Jun Yi Da Xue Xue Bao, 2004 Dec, 24(12), 1379 - 81
{Effect of saikosaponins on epileptic rat electroenciphalogram.}; Huang YS et al.; OBJECTIVE: To study the effect of saikosaponins on the electroencephalogram (EEG) of epileptic rats to evaluate its therapeutic effect against epilepsies . METHODS: Sixty 8-week-old healthy SD rats were randomized into normal control group (A), epileptic model group (B), lamotrigine group (C), and 3 saikosaponin groups of small, moderate and high doses (D, E, and F groups, respectively), with 10 rats in each group . Penicillin was used to induce epilepsy in the latter 5 groups, and the EEG and onset of epileptic seizures were observed in each group . RESULTS: In group B, the EEG contained obvious epileptic discharges, which were not found in that in group A . After treatment with saikosaponins and lamotrignie, the EEG of group C and F became normal, whereas the EEG in group D still contained epileptic discharges at a low level, and that in group E was basically normal . The EEGs of group C, D, E, and F were significantly different from that in group B (P<0.001) . CONCLUSION: Saikosaponins can obviously alleviate the severity of epileptic seizure in epileptic rats.

J Bacteriol, 2005 Jan, 187(1), 54 - 64
Localization of MreB in Rhodobacter sphaeroides under conditions causing changes in cell shape and membrane structure; Slovak PM et al.; MreB is thought to be a bacterial actin homolog that defines the morphology of rod-shaped bacteria . Rhodobacter sphaeroides changes shape, from a rod to coccobacillus, and undergoes extensive cytoplasmic membrane invagination when it switches from aerobic to photoheterotrophic growth . The role of MreB in defining R . sphaeroides shape was therefore investigated . Attempts at deleting or insertionally inactivating mreB were unsuccessful under all growth conditions . Immunofluorescence microscopy showed MreB localized to mid-cell in elongating cells under both aerobic and photoheterotrophic conditions . Three-dimensional reconstruction showed that MreB formed a ring at mid-cell . MreB remained at mid-cell as septation began but localized to new sites in the daughter cells before the completion of septation . MreB localized to putative septation sites in cephalexin-treated filamentous cells . Genomic single-copy mreB was replaced with gfp-mreB, and green fluorescent protein (GFP)-MreB localized in the same pattern, as seen with immunofluorescence microscopy . Some of the cells expressing GFP-MreB were abnormal, principally displaying an increase in cell width, suggesting that the fusion was not fully functional in all cells . GFP-MreB localized to swellings at mid-cell in cells treated with the penicillin-binding protein 2 inhibitor amdinocillin . These data suggest that MreB is essential in R . sphaeroides, performing a role at mid-cell in elongating cells, and in early septation, putatively in the cytoplasmic control of the peptidoglycan synthetic complexes.

Ren Fail, 2004 Nov, 26(6), 655 - 61
Acute renal failure: a common manifestation of leptospirosis; Cetin BD et al.; Leptospirosis is an infectious disease caused by pathogenic leptospires and may vary in degree from an asymptomatic infection to severe and fatal illness . Sixteen patients (all males; aged 40+/-17 years) with leptospirosis were admitted to Sisli Etfal Training and Research Hospital between July 1998 and August 2003 and were retrospectively reviewed . Age, gender, occupation, clinical presentation, laboratory features, seasonal distribution of the disease, diagnostical approach, and prognostic factors were evaluated . Eleven patients were cured with no complication; four patients died of hepatic and/or renal failure . Eight patients presented with acute renal failure; seven of them needed dialytic support . One patient developed chronic renal failure and had to undergo regular hemodialysis . All deceased patients (aged 61+/-7 years) were anuric at admission and their serum bilirubin changed between 39-44 mg/dL (mean 41.3+/-2.2 mg/dL) . Cured patients ranged in age from 14-62 years (34+/-14 years) and their serum bilirubin levels ranged from 9-35 mg/dL (23.1+/-11.4 mg/dL) . Crystalline penicillin G 12 million U/day was administered to all patients . Six patients also received hepatic coma treatment . This study emphasizes that leptospirosis presenting with renal failure is a severe disease, and mortality is frequently related to delays in diagnosis due to lack of clinical understanding . The association of acute renal failure and jaundice should lead the clinician to suspect leptospirosis . We concluded that old age, oliguria/anuria, high serum bilirubin levels (>36 mg/dL), and high serum potassium levels might be risk factors that increase mortality in leptospirosis.

Curr Opin Investig Drugs, 2004 Aug, 5(8), 823 - 6
Metallo-beta-lactamase inhibitors: promise for the future?
Toney JH, Moloughney JG.
Carbapenem resistance continues to erode the effectiveness of antibiotics such as imipenem and meropenem in the clinic . Resistance mechanisms can include interplay between porin loss (membrane permeability), mutation of penicillin binding proteins necessary for cell division, and expression of class A, B and D beta-lactamases . Bacterial resistance to beta-lactams such as penicillin or amoxicillin has been overcome in the clinic using several strategies, including development of antibiotics not susceptible to hydrolysis by beta-lactamases, or co-administration of the antibiotic with beta-lactamase inhibitors . This overview will focus on progress since 2000 in identifying inhibitors of class B, or metallo-beta-lactamases with the aim of reversing carbapenem resistance.

Clin Dermatol, 2004 Nov-Dec, 22(6), 461 - 8
Syphilis; Zeltser R et al.; In the last half of the 20(th) century, medicine has made tremendous inroads against syphilis chiefly owing to the introduction of penicillin and vigorous public health initiatives . Yet, the world continues to be burdened by this disease . Since 2000, overall rates of syphilis have risen in the US and throughout the world . Furthermore, through its association with an increased risk of HIV infection, syphilis has acquired a new potential for morbidity and mortality . The aim of this review is to survey the latest knowledge about syphilis, including pathogenesis and host response, clinical manifestations, diagnostic methods and, especially, treatment and follow-up.

Eur J Obstet Gynecol Reprod Biol, 2005 Jan 10, 118(1), 77 - 80
Actinomyces infection in female genital tract; Kayikcioglu F et al.; Objectives: To analyze clinical and laboratory characteristics of patients with pelvic actinomyces . Study design: We studied five patients with pelvic actinomyces who were admitted between January 1, 2002 and December 31, 2002 . The initial complaints, diagnostic methods, therapeutic alternatives and results of the therapies were examined . Results: The ages of the cases varied between 32 and 52 years old . All five patients had been using an intrauterine device . Three cases had hydronephrosis due to infection . Two patients were diagnosed postoperatively while the other three cases were diagnosed with cervical smear and endometrial biopsy; penicillin G was administered to all . The patients are still under surveillance, and without any problems . Conclusion: In patients with an intrauterine device, actinomyces should be remembered in differential diagnosis of pelvic infections . Preoperative diagnosis is of the utmost importance in order to prevent morbidity of this infiltrative infection . Long-term penicillin therapy proved to be successful . Complicated or resistant cases to medical therapy should be candidates for surgical therapy.

Toxicology, 2005 Jan 15, 206(2), 257 - 72
Detection of immunotoxicity using T-cell based cytokine reporter cell lines ("Cell Chip"); Ringerike T et al.; Safety assessment of chemicals and drugs is an important regulatory issue . The evaluation of potential adverse effects of compounds on the immune system depends today on animal experiments . An increasing demand, however, exists for in vitro alternatives . Cytokine measurement is a promising tool to evaluate chemical exposure effects on the immune system . Fortunately, this type of measurement can be performed in conjunction with in vitro exposure models . We have taken these considerations as the starting point to develop an in vitro method to efficiently screen compounds for potential immunotoxicity . The T-cell lymphoma cell line EL-4 was transfected with the regulatory sequences of interleukin (IL)-2, IL-4, IL-10, interferon (IFN)-gamma or actin fused to the gene for enhanced green fluorescent protein (EGFP) in either a stabile or a destabilised form . Consequently, changes in fluorescence intensity represent changes in cytokine expression with one cell line per cytokine . We used this prototype "Cell Chip" to test, by means of flow cytometry, the immunomodulatory potential of 13 substances and were able to detect changes in cytokine expression in 12 cases (successful for cyclosporine, rapamycin, pentamidine, thalidomide, bis(tri-n-butyltin)oxide, house dust mite allergen (Der p I), 1-chloro-2,4-dinitrobenzene, benzocaine, tolylene 2,4-diisocyanate, potassium tetrachloroplatinate, sodium dodecyl sulphate and mercuric chloride; unsuccessful for penicillin G) . In conclusion, this approach seems promising for in vitro screening for potential immunotoxicity, especially when additional cell lines besides T-cells are included.

Neurosci Behav Physiol, 2004 Oct, 34(8), 797 - 802
The effects of electrical stimulation of the paleocerebellar cortex on penicillin-induced convulsive activity in rats; Godlevskii LS et al.; Studies in Wistar rats in conditions of free behavior showed that low-frequency stimulation of the paleocerebellar cortex (nodulus, uvula) (10-12 Hz, 0.5 msec) was accompanied by activation of spike discharges induced by systematic application of benzylpenicillin sodium (3,000,000 IU/kg) . Facilitation of the formation of ictal discharges was also seen . High-frequency electrical stimulation (100-300 Hz, 0.25 msec) of the same structure was accompanied by suppression of the generation of spike potentials and prevented the development of ictal potentials . The antiepileptic effect of electrical stimulation was seen in conditions of relatively low levels of convulsive activity . Electrical stimulation decreased the frequency and amplitude of spike potentials in the interstimulus intervals and decreased the total duration of epileptic foci . Repeated electrical stimulation of the paleocerebellum after electrocoagulation did not produce any changes in convulsive activity.

Epilepsy Behav, 2004 Dec, 5(6), 847 - 51
Acute effect of an extract of Ambrosia paniculata (Willd.) O . E . Schultz (mugwort) in several models of experimental epilepsy; Buznego MT et al.; The acute effect of Ambrosia paniculata was studied in several animal models of epilepsy . Intraperitoneal injections (0.01 mL/g body wt) of a decoction of the dry leaves significantly enhanced the latency to the first convulsion and survival time in mice injected with picrotoxin (7 mg/kg) or isoniazid (210 mg/kg) . Epileptic spikes were induced by topical application of penicillin through a glass electrode filled with a penicillin-agar-saline mixture and recorded in sensorimotor and occipital cortices, in rats immobilized with d-tubocurarine . The plant decoction reduced significantly the spike amplitude in both sites . The mentioned effects were elicited at doses that also reduced general motor activity (Irwin test) and exploratory behavior . The decoctions were not effective against electroshock-induced convulsions in mice . The convulsions induced by isoniazid, picrotoxin, and penicillin differed from those induced by electroshock implicating selective disruption of GABAergic neurotransmission . The results suggest that A . paniculata, like several conventional antiepileptic drugs, might act by enhancing GABAergic neurotransmission, a hypothesis that requires further demonstration . These results explain and justify the traditional use of the plant in epilepsy.

Patient Educ Couns, 2004 Dec, 55(3), 371 - 8
Do pictograms improve children's understanding of medicine leaflet information?
Hameen-Anttila K, Kemppainen K, Enlund H, Bush Patricia J, Marja A.
There is a growing need for balanced drug information customized for special target groups such as children {Food and Drug Administration . Prescription Drug Product Labeling; Medication Guide Requirements; Proposed Rule . Part VII . Department of Health and Human Services, 21 CRF Part 201, et al . Federal Register 1995;60:44182-252; Dickinson D, Raynor DK, Duman M . Patient information leaflets for medicines: using consumer testing to determine the most effective design . Patient Educ Couns 2001;43:147-59} . Pictograms are one aid that may be used to make information easier to read and understand . The aim of this study was to test whether children understand pictograms developed by the United States Pharmacopeia (USP) {The United States Pharmacopeial Convention Inc . USP Pictograms . Retrieved 11 March 2002 from }, and especially, if the pictograms improve children's understanding of medicine leaflet information . Finnish elementary school children aged 7 years (n=28), 11 years (n=31) and 13 years (n=31) were interviewed and asked what they thought 15 USP pictograms mean . The two older age groups were also asked to read an "easy-to-read" leaflet for penicillin-V . Every second child was given a leaflet with a plain text and the others received the same text accompanied by pictograms . After reading the leaflet, the children were asked seven questions related to the text . Most of the children understood the meanings of the selected 15 pictograms correctly, the proportion of the correct explanations varying from 30 to 99% according to the pictogram . Even well-understood pictograms did not help the children understand the leaflet information, although they reduced the need for probing . This study shows that the context in which pictograms are tested makes a difference in the results . Testing plain pictograms without incorporating them in their real context, e.g., in the patient information leaflet may exaggerate their usefulness in leaflet information.

J Bacteriol, 2004 Dec, 186(24), 8370 - 9
Functional analysis of the cell division protein FtsW of Escherichia coli; Pastoret S et al.; Site-directed mutagenesis experiments combined with fluorescence microscopy shed light on the role of Escherichia coli FtsW, a membrane protein belonging to the SEDS family that is involved in peptidoglycan assembly during cell elongation, division, and sporulation . This essential cell division protein has 10 transmembrane segments (TMSs) . It is a late recruit to the division site and is required for subsequent recruitment of penicillin-binding protein 3 (PBP3) catalyzing peptide cross-linking . The results allow identification of several domains of the protein with distinct functions . The localization of PBP3 to the septum was found to be dependent on the periplasmic loop located between TMSs 9 and 10 . The E240-A249 amphiphilic peptide in the periplasmic loop between TMSs 7 and 8 appears to be a key element in the functioning of FtsW in the septal peptidoglycan assembly machineries . The intracellular loop (containing the R166-F178 amphiphilic peptide) between TMSs 4 and 5 and Gly 311 in TMS 8 are important components of the amino acid sequence-folding information.

J Bacteriol, 2004 Dec, 186(24), 8326 - 36
Endopeptidase penicillin-binding proteins 4 and 7 play auxiliary roles in determining uniform morphology of Escherichia coli; Meberg BM et al.; The low-molecular-weight (LMW) penicillin-binding protein, PBP 5, plays a dominant role in determining the uniform cell shape of Escherichia coli . However, the physiological functions of six other LMW PBPs are unknown, even though the existence and enzymatic activities of four of these were established three decades ago . By applying fluorescence-activated cell sorting (FACS) to quantify the cellular dimensions of multiple PBP mutants, we found that the endopeptidases PBP 4 and PBP 7 also influence cell shape in concert with PBP 5 . This is the first reported biological function for these two proteins . In addition, the combined loss of three DD-carboxypeptidases, PBPs 5 and 6 and DacD, also impaired cell shape . In contrast to previous reports based on visual inspection alone, FACS analysis revealed aberrant morphology in a mutant lacking only PBP 5, a phenotype not shared by any other strain lacking a single LMW PBP . PBP 5 removes the terminal D-alanine from pentapeptide side chains of muropeptide subunits, and pentapeptides act as donors for cross-linking adjacent side chains . As endopeptidases, PBPs 4 and 7 cleave cross-links in the cell wall . Therefore, overall cell shape may be determined by the existence or location of a specific type of peptide cross-link, with PBP 5 activity influencing how many cross-links are made and PBPs 4 and 7 acting as editing enzymes to remove inappropriate cross-links.

Acad Emerg Med, 2004 Dec, 11(12), 1268 - 71
Efficacy of penicillin for dental pain without overt infection; Runyon MS et al.; OBJECTIVES: Dental pain is a common presenting symptom in the acute care setting . Even in the absence of overt infection, many physicians routinely prescribe antibiotics such as penicillin . The authors sought to test the hypothesis that penicillin is not necessary or beneficial in the treatment of undifferentiated dental pain without overt infection . METHODS: This prospective, randomized, double-blind, placebo-controlled trial was conducted at an urban teaching hospital with approximately 105,000 emergency department visits per year . A convenience sample of adult emergency department patients presenting with dental pain and no clinically overt infection was randomized to receive penicillin or placebo . A structured evaluation was performed at enrollment and again at a 5- to 7-day follow-up visit . The main outcome measure was evidence of overt dental infection at the 5- to 7-day follow-up visit . RESULTS: A total of 195 patients were enrolled . Ninety-eight (50%) were randomized to treatment with penicillin . A total of 125 patients (64%) were followed up . Outcome data were identified for nine additional study patients, who returned to the dental clinic or emergency department outside of the scheduled follow-up period and were included in the final analysis . Overall, 13 of 134 patients (9%) developed signs of infection: six of 64 (9%) from the penicillin group and seven of 70 (10%) from the placebo group (p = 0.90) . There was no significant difference between the penicillin and placebo groups in baseline characteristics, medication compliance, or visual analog scale pain scores at enrollment . CONCLUSIONS: These data support the hypothesis that penicillin is neither necessary nor beneficial in the treatment of undifferentiated dental pain in the absence of overt infection.

Rapid Commun Mass Spectrom, 2005, 19(1), 9 - 14
Average peptide score: a useful parameter for identification of proteins derived from database searches of liquid chromatography/tandem mass spectrometry data; Chepanoske CL et al.; The quantity and variable quality of data that can be generated from liquid chromatography (LC)/mass spectrometry (MS)-based proteomics analyses creates many challenges in interpreting the spectra in terms of the actual proteins in a complex sample . In spite of improvements in algorithms that match putative peptide sequences to MS/MS spectra, the assembly of these lists of possible or probable peptides into a 'correct' set of proteins is still problematic . We have observed a trend in a simple relationship, derived from standard database search outputs, which can be useful in assessing the quality of a MS/MS-based protein identification . Specifically, the ratio of the protein score and number of non-redundant peptides, or average peptide score (APS), can facilitate initial filtering of database search results in addition to providing a useful measure of confidence for the proteins identified . This parameter has been applied to results from the analysis of multi-protein complexes derived from pull-down experiments analyzed using a two-dimensional LC/MS/MS workflow . In particular, the complex list of protein identifications derived from a drug affinity pull-down with immobilized ampicillin and an E . coli lysate was greatly simplified by applying the APS as a filter, allowing for facile identification of the penicillin-binding proteins known to interact with ampicillin . Furthermore, an APS threshold can be used for any data sets derived from electrospray ionization (ESI)- or matrix-assisted laser desorption/ionization (MALDI)-MS/MS experiments and is also not specific to any database search program.

J Med Screen, 2004, 11(4), 175 - 9
Identifying homozygous sickle cell disease when neonatal screening is not available: a clinic-based observational study; Hambleton IR et al.; OBJECTIVES: Life-threatening clinical complications can occur in the first years of life in people with homozygous sickle cell disease . There is consensus that a clinical care programme comanaged by a specialist clinic should follow early-life disease identification . In a setting without widespread neonatal screening for this disease, we predict the percentage of affected births that enrol in specialist clinics during childhood, and the percentage that enrol early enough to benefit from penicillin prophylaxis (which is offered until five years of age) . SETTING: A retrospective study of enrolment between 1973 and 1999 at three clinics in Jamaica, the country's only referral centres for sickle cell disease . RESULTS: Among enrolees not screened at birth, observed enrolment by age five was 10.1% (95% confidence interval {CI} 5.7-16.7%) among 1974 births, which is predicted to rise to 35.7% (95% CI 35.0-36.4%) among 1999 births . Observed enrolment by 18 years of age was 45.9% (95% CI 35.7-58.2%) among 1974 births, which is predicted to peak at 61.9% (95% CI 60.5-63.2%) among 1984 births, and fall to 48.9% (95% CI 40.9-56.9%) among 1999 births . Median age at enrolment was 10.5 years (95% CI 10.0-11.3) . CONCLUSIONS: Based on 1999 estimates, almost 65% of children affected by homozygous sickle cell disease not identified at birth will not benefit from important early-life clinical intervention, and half will not enrol for specialised care by their 18th birthday . Among patients that enrol, half do so in adolescence when management is less focused on preventive care.

Bioorg Khim, 2004 Sep-Oct, 30(5), 451 - 7
{A new N-acyl derivative of (S)-cysteine for quantitative determination of enantiomers of amino compounds by HPLC with a precolumn modification with o-phthalaldehyde}; Renal involvement in leptospirosis at Dr . Cipto Mangunkusumo and Persahabatan Hospitals; Department of Internal Medicine, Faculty of Medicine, University of Indonesia-Dr . Cipto Mangunkusumo National Central General Hospital, JakartaAIM: To describe clinical pattern of ARF caused by leptospirosis and its related factors . METHODS: A cross-sectional study using medical record data of all leptospirosis cases admitted to Cipto Mangunkusumo and Persahabatan General Hospitals between January 1993 and December 1996 . Patient identification included age, sex, and occupation . Clinical symptoms were described in details and followed by laboratory testing i.e . peripheral blood count, urinalysis, blood urea and creatinine, liver function test, and pancreatic enzymes assay . RESULTS: Seventy-five percent were men and the mean age was 38.3 years old . Sixty out of 68 (88.2%) patients had ARF as defined by an increase of plasma creatinine level of >1.5 mg/mL . The most common presenting symptoms in patients with ARF were fever (100%), nausea and vomiting (95.0%), muscle pain (88.1%) and jaundice (71.3%) . The mean duration of fever 7.2 days . The most frequent laboratory abnormalities were increased erythrocyte sedimentation rate (100%), leukocytosis (90%) and increase total bilirubin level (87.5%) . Only leukocytosis showed a significant difference between ARF and non-ARF patients (p=0,014) . Leptospira bataviae was found in 95.6% of patients and 96.7% of ARF patients . Penicillin was given to 80.9% of patients with only 2 (2.9%) deaths . CONCLUSION: Although significant correlation cannot be established, we concluded that nausea, vomiting, muscle pain, jaundice, increased ESR and total bilirubin level should alert the physician about the possibility of renal involvement in leptospirosis patients with prolonged fever . Leptospira bataviae was an important virulent pathogen . Treatment with penicillin may significantly improve organ failure and was considered the drug of choice in managing leptospiral infection.

Bioorg Med Chem, 2004 Dec 15, 12(24), 6473 - 94
Synthesis of mono- and disaccharide analogs of moenomycin and lipid II for inhibition of transglycosylase activity of penicillin-binding protein 1b; Garneau S et al.; Three types of mono- and disaccharides 3a,b, 4a-c, 5, and some chaetomellic acid A analogs 6 and 42-44 were synthesized as potential inhibitors of the transglycosylase activity of penicillin-binding protein 1b (PBP1b), a key bacterial enzyme responsible for the formation of the polysaccharide backbone of peptidoglycan as well as for cross-linking of its peptide portions . The target compounds combine structural features of both the active portion of moenomycin and the natural PBP1b substrate, lipid II . The desired skeletons were obtained in a convergent fashion involving attachment of the lipid-alkylated glyceric acid moieties 11a,b to the corresponding carbohydrate-containing phosphonic acids 23, 24a, and 24b . Compounds 3a,b were prepared to verify the distance requirements between the sugar and the noncleavable C-phosphonate moieties . Compounds 4a-c were synthesized to examine the importance of the first sugar unit of moenomycin, a known inhibitor of transglycosylase catalysis by PBP1b, with respect to antibiotic activity . These were prepared by condensation of 11a,b with 28a and 28c, which were made by glycosylation of 3-bromopropanol with oxazolines 25a,b, and Arbuzov reaction with triethyl or trimethyl phosphite, followed by dealkylation with bromotrimethylsilane . Compound 5 was generated to verify the possibility of using a dicarboxylate group to mimic the diphosphate of lipid II . It was synthesized by coupling of alcohol 31 with alpha-trichloroacetimidate 34 . Chaetomellic acid A analogs were prepared by a Michael addition to dimethyl acetylenedicarboxylate . With the exception of 3b, all of the target compounds were found to inhibit PBP1b, albeit with modest potency.

J Pharm Sci . 2004 Nov 17;94(1):102-113 {Epub ahead of print}
Dendrisomes: Vesicular structures derived from a cationic lipidic dendron; Al-Jamal KT et al.; The behavior of a novel synthetic lipidic cationic lysine-based dendron (partial dendrimer) in aqueous media and its ability, with and without cholesterol, to self-assemble into higher order structures was studied to gain an understanding of these structures as potential drug carriers . The dendron was prepared by solid-phase peptide synthesis . A reverse-phase evaporation (REV) technique was used to prepare cationic vesicular aggregates of the dendron with different molar ratios of cholesterol . The size and zeta potential of these supramolecular aggregates or "dendrisomes" was determined by photon correlation spectroscopy (PCS) . Dendrisome morphology and thermotropic properties were studied by transmission electron microscopy (TEM) and differential scanning calorimetry (DSC) . Radiolabeled penicillin G was used as a model of a negatively charged water-soluble compound to investigate the encapsulation efficiency of the dendrisomes . In vitro release of the drug was determined using as a comparator a REV liposome formulation . Dendrisomes of all compositions have higher encapsulation efficiencies and slower release rates compared to the comparator . Cholesterol was found both to increase the size of the aggregates from around 310 to 560 nm and to increase shape irregularities, but did not change the positive zeta potential, in the order of +50 mV, of the dendrisomes . Cholesterol decreases penicillin G entrapment efficiency but increases solute leakage at 25 degrees C . (c) 2004 Wiley-Liss, Inc . and the American Pharmacists Association J Pharm Sci 94:102-113, 2005.

Trop Med Int Health, 2004 Nov, 9(11), 1216 - 21
Treatment of maternal syphilis in rural South Africa: effect of multiple doses of benzathine penicillin on pregnancy loss; Myer L et al.; OBJECTIVES: Despite few data, the treatment of syphilis in pregnant women using a single dose of benzathine penicillin is the standard of care in many resource-poor settings . We examined the effect of various doses of benzathine penicillin on pregnancy loss among women with a positive Rapid Plasma Reagin (RPR) test result in a rural South African district . METHODS: All pregnant women making their first antenatal care visit during pregnancy were screened for syphilis using the RPR test . Those testing positive were counselled to receive three weekly doses of benzathine penicillin, and received a partner notification card . Pregnancy outcomes were determined from facility records or home visits where necessary . RESULTS: Of 8917 women screened, 1043 (12%) had reactive syphilis serology; of those with titre data available, 30% had titres of 1:8 or greater . While 41% (n = 430) of women received all three doses as counselled, 30% (n = 312) received only one dose, and 20% (n = 207) did not return to the clinic to receive treatment . Among the 947 women with pregnancy outcome data available, there were 17 miscarriages and 48 perinatal deaths observed . There was a strong trend towards reduced risk of pregnancy loss among women receiving multiple doses of penicillin (adjusted OR for perinatal mortality for each additional dose received, 0.63; 95% CI, 0.48-0.84) . CONCLUSIONS: While this association requires further investigation, these results suggest that there may be substantial benefit to providing multiple doses of benzathine penicillin to treat maternal syphilis in this setting.

Clin Infect Dis, 2004 Nov 15, 39(10), 1417 - 24 Epub 2004 Oct 26.
An open, randomized, controlled trial of penicillin, doxycycline, and cefotaxime for patients with severe leptospirosis; Suputtamongkol Y et al.; BACKGROUND: Leptospirosis is an important cause of fever in the rural tropics . Since 1996, there has been a marked increase in the incidence of leptospirosis in northeastern Thailand . Although leptospirosis generally is susceptible to antibiotics, there is no consensus regarding the optimal treatment for severe leptospirosis . METHODS: An open-label, randomized comparison of parenteral cefotaxime, penicillin G sodium (hereafter known as "penicillin G"), and doxycycline for the treatment of suspected severe leptospirosis was conducted . The study involved 540 patients admitted to 4 hospitals in northeastern Thailand . RESULTS: A total of 264 patients (48.9%) had leptospirosis confirmed by serologic testing or culture . The overall mortality rate was 5% . There were no significant differences between the antibiotics with regard to associated mortality, defervescence, or time to resolution of abnormal findings of laboratory tests either among all study participants or among the subgroup of patients with confirmed leptospirosis . A total of 132 patients had rickettsial infection diagnosed, and, for these patients, treatment with doxycycline was superior to treatment with penicillin G . CONCLUSIONS: Doxycycline or cefotaxime is a satisfactory alternative to penicillin G for the treatment of severe leptospirosis.

Dtsch Med Wochenschr, 2004 Nov 19, 129(47), 2535 - 7
{Disseminated intravascular coagulation, perimyocarditis and bilateral pleural empyema in adult Still's disease}; Krzossok S et al.; HISTORY: A 21-year-old man was admitted to the hospital because of high fever, arthralgias and myalgias . One week before he was treated with penicillin G orally because of cough and sore throat . PHYSICAL EXAMINATION: The critically ill patient presented with a red throat and cervical lymphadenopathy . Lung auscultation revealed reduced respiratory sounds at both base, heart auscultation revealed a pericardial friction rub . Dermatologic examinations were normal . INVESTIGATIONS: Laboratory findings were notable for anemia, thrombopenia and leukocytosis, disseminated intravascular coagulation and markedly elevated CRP (309 mg/l) . Electrogram showed inferior and lateral ST segment depression . Echocardiography showed pericardial effusion . Chest CT scan revealed bilateral pleural effusion, a left-sided small infiltrate and enlarged mediastinal lymph nodes . Abdominal ultrasound confirmed hepatosplenomegaly and ascites . TREATMENT AND CLINICAL COURSE: A diagnosis of parapneumonic bilateral pleural empyema, perimyocarditis and disseminated intravascular coagulation was made . Despite institution of empiric antibiotic therapy, no clinical improvement was observed . After exclusion of infectious, autoimmune or malignant disease, clinical and laboratory data, especially marked hyperferritinemia, helped to establish the diagnosis of adult-onset Still's disease . Immunosuppressive treatment with prednisolone and azathioprin resulted in remission . CONCLUSION: Adult-onset Still's disease is a rare inflammatory disorder of unknown origin, which may affect multiple organs . The diagnosis is based on a diagnostic score, which includes a number of clinical and laboratory findings, published by Yamaguchi in 1992 . Marked hyperferritinemia represents an additional diagnostic clue to the disease.

J Pharm Biomed Anal, 2004 Nov 19, 36(4), 701 - 9
Ion selective electrodes for penicillin-G based on Mn(III)TPP-Cl and their application in pharmaceutical formulations control by sequential injection analysis; Santos EM et al.; The work describes the construction, evaluation and analytical application of ion selective electrodes sensitive to penicillin-G antibiotics for pharmaceutical products analysis . Different types of polymeric membranes based on PVC (poly(vinyl chloride)) and EVA (ethyl-vinyl-acetate), without internal reference solution, were prepared using 5,10,15,20-tetraphenylporphyrinate (TPP) manganese(III) (Mn(III)TPP-Cl) as electroactive material . Different additives such as tetra-n-octylammoniumbromide (cationic additive) and sodium tetraphenylborate (anionic additive) were incorporated into the membranes to evaluate their influence on electrodes performance . The comparison of the developed detectors was based on general analytical characteristics, selectivity and lifetime . To accomplish the analysis of real samples, two selective membranes composed of 33.0% (w/w) of PVC, 66.0% (w/w) of o-NPOE and 1.0% (w/w) of Mn(III)TPP-Cl (type A) and 33.0% (w/w) of PVC, 66.0% (w/w) of o-NPOE, 1.0% (w/w) of Mn(III)TPP-Cl and 10% mol (relative to the molar concentration of Mn(III)TPP-Cl) of sodium tetraphenylborate (type B) were used . Type A electrode presented a linear response between 2 x 10(-5) and 10(-1) moll(-1) for penicillin-G, a slope of about -59 mVdec(-1) and a reproducibility of about +/-0.5 mVday(-1), while type B exhibited a linear response between 5 x 10(-5) and 10(-1) moll(-1) for penicillin-G, a slope of about -61 mVdec(-1) and a reproducibility of about +/-0.3 mV day(-1) . The potentiometric analysis of penicillin-G in pharmaceutical products was carried out by direct potentiometry and the results obtained were compared with those provided by the HPLC reference method . These membranes (type A and type B) were used to prepare tubular electrodes that were coupled to a sequential injection system (SIA) and presented a linear range between 2 x 10(-4) and 1 x 10(-2) moll(-1) and slopes of -59.3 +/- 0.8 and -57.3 +/- 1.2 mVdec(-1), respectively . The tubular electrode constructed using type B membrane (type TB) was used to carry out the potentiometric analysis of penicillin-G in pharmaceutical formulations . The proposed procedure enabled relative errors between 0.1% and 1.2% (n = 4) and a sampling-rate of about 25 samples per h.

J Vet Med A Physiol Pathol Clin Med, 2004 Sep-Oct, 51(7-8), 363 - 4
Actinomycosis in a one-humped camel (Camelus dromedarius); Kilic N et al.; An actinomycotic granuloma caused by Actinomyces viscosus is reported in a dromedary camel . Two hard, cutaneous, large granulamatous nodules were present on both sides of the postero-ventral side of the mandible exhibiting exudation and necrosis . After radical excision of the lesion, the daily treatment with penicillin-streptomycin combination was continued for 4 weeks . About 8 and 24 weeks from the initial treatment, no new nodules were noticed.

Int J Dermatol, 2004 Nov, 43(11), 847 - 51
Prospective, noncomparative open study from Kuwait of the role of intravenous immunoglobulin in the treatment of toxic epidermal necrolysis; Al-Mutairi N et al.; BACKGROUND: High-dose intravenous immunoglobulin (IVIG) is emerging as a promising new therapy for treating the rare but potentially fatal drug reaction toxic epidermal necrolysis (TEN) . Experimental in vitro studies support that IVIG can block the Fas-FasL-mediated apoptosis in TEN . METHODS: Twelve consecutive patients (7M, 5F) with TEN admitted over a 5-year period from January 1998 to December 2002 were treated with a dose of 0.5-1.0 g/kg/d of IVIG for 4-5 days along with standard care protocol . Clinical outcome in terms of average duration to arrest the progression, complete healing, hospital stay, side-effects and complications were determined to find the efficacy of IVIG treatment . RESULTS: Average age was 27.16 years (7-50 years) . There were four children (2M, 2F) aged 7-12 years . One patient had an underlying malignancy . No patient had HIV infection . The average total body surface area involvement was 57.5% (30-90%) . An IVIG infusion was started, on average, 1.58 days (1-3 days) after admission . All patients responded well to the treatment . There was no mortality . The disease progression was arrested in a mean of 2.83 days (1-5 days) . Time taken for complete healing (re-epithelialization) was 7.33 days (5-13 days) . The average duration of hospital stay was 12.5 days (7-21 days) . No side-effects of the IVIG treatment were observed in these patients . The drugs triggering TEN in these patients were phenytoin (four patients), followed by penicillin (three), cotrimoxazole (two), phenobarbital and furosemide (one patient each), respectively . In one patient, the offending drug could not be ascertained . CONCLUSION: Our experience of treating 12 patients with TEN using IVIG, in Kuwait, confirms that it is a safe and effective treatment for these patients.

Biomacromolecules, 2004 Nov-Dec, 5(6), 2201 - 11
Interactions of two amphiphilic penicillins with myoglobin in aqueous buffered solutions: a thermodynamic and spectroscopy study; Taboada P et al.; The interactions and complexation process of the amphiphilic penicillins sodium cloxacillin and sodium dicloxacillin with horse myoglobin in aqueous buffered solutions of pH 4.5 and 7.4 have been examined by equilibrium dialysis, zeta-potential, isothermal titration calorimetry (ITC) and UV-Vis absorbance techniques . A more opened structure of the protein molecules is detected as a consequence of the reduction of pH from 7.4 to 4.5 . Binding isotherms and derived Hill coefficients reflect a cooperative binding behavior . Gibbs energies of binding per mole of drug were obtained from equilibrium dialysis data and compared with those derived from the zeta potential taking into account cooperativity . DeltaGads degrees values so obtained are large and negative at low concentrations where binding to the "high-energy" sites occurs and decreases with the drug concentration . The enthalpies of binding have been obtained from ITC and are small and exothermic so that the Gibbs energies of binding are dominated by large increases in entropy consistent with hydrophobic interactions . Other thermodynamic quantities of the binding mechanism, that is, entropy, DeltaSITCi, Gibbs energy, DeltaGITCi, the binding constant, KITCi, and the number of binding sites, ni, were also obtained, confirming the above results . From ITC data and following a theoretical model, the number of bound and free penicillin molecules was calculated, being higher at pH 4.5 than at pH 7.4 . The binding of penicillin causes a conformational transition on protein structure as a consequence of the resulting intramolecular repulsion between the penicillin molecules bound to the protein . Thermodynamic quantites (the Gibbs energy of the transition in water, DeltaGw degrees , and in a hydrophobic environment, DeltaGhc degrees) of the denaturation process were calculated, indicating that at pH 4.5 some of the histidine residues are protonated, becoming accessible to solvent and giving rise to a more opened protein structure.

J Vet Med Sci, 2004 Oct, 66(10), 1301 - 4
Chloramphenicol treatment for rabbit syphilis; Saito K et al.; Penicillin, the recommended treatment for rabbit syphilis, sometimes induces adverse effects . The efficacy of oral chloramphenicol was evaluated in 39 cases of rabbit syphilis to establish a safe and efficient treatment for this disease in companion rabbits . All cases clinically improved and recovered promptly . Fourteen of 39 cases (35.9%) relapsed, but most remained chloramphenicol sensitive . Since safety take priority over efficacy in treating syphilis in companion rabbits, chloramphenicol should be chosen as a first-line agent, as a general rule . Three-week administration of chloramphenicol may be adequate at the initial onset of disease . When relapse occurs repeatedly or the rabbit owner cannot administer the medicine adequately, treatment with penicillin should be considered.

Adv Microb Physiol, 2004, 49, 1 - 76
Glutathione, altruistic metabolite in fungi; Pocsi I et al.; Glutathione (GSH; gamma-L-glutamyl-L-cysteinyl-glycine), a non-protein thiol with a very low redox potential (E'0 = 240 mV for thiol-disulfide exchange), is present in high concentration up to 10 mM in yeasts and filamentous fungi . GSH is concerned with basic cellular functions as well as the maintenance of mitochondrial structure, membrane integrity, and in cell differentiation and development . GSH plays key roles in the response to several stress situations in fungi . For example, GSH is an important antioxidant molecule, which reacts non-enzymatically with a series of reactive oxygen species . In addition, the response to oxidative stress also involves GSH biosynthesis enzymes, NADPH-dependent GSH-regenerating reductase, glutathione S-transferase along with peroxide-eliminating glutathione peroxidase and glutaredoxins . Some components of the GSH-dependent antioxidative defence system confer resistance against heat shock and osmotic stress . Formation of protein-SSG mixed disulfides results in protection against desiccation-induced oxidative injuries in lichens . Intracellular GSH and GSH-derived phytochelatins hinder the progression of heavy metal-initiated cell injuries by chelating and sequestering the metal ions themselves and/or by eliminating reactive oxygen species . In fungi, GSH is mobilized to ensure cellular maintenance under sulfur or nitrogen starvation . Moreover, adaptation to carbon deprivation stress results in an increased tolerance to oxidative stress, which involves the induction of GSH-dependent elements of the antioxidant defence system . GSH-dependent detoxification processes concern the elimination of toxic endogenous metabolites, such as excess formaldehyde produced during the growth of the methylotrophic yeasts, by formaldehyde dehydrogenase and methylglyoxal, a by-product of glycolysis, by the glyoxalase pathway . Detoxification of xenobiotics, such as halogenated aromatic and alkylating agents, relies on glutathione S-transferases . In yeast, these enzymes may participate in the elimination of toxic intermediates that accumulate in stationary phase and/or act in a similar fashion as heat shock proteins . GSH S-conjugates may also form in a glutathione S-transferases-independent way, e.g . through chemical reaction between GSH and the antifugal agent Thiram . GSH-dependent detoxification of penicillin side-chain precursors was shown in Penicillium sp . GSH controls aging and autolysis in several fungal species, and possesses an anti-apoptotic feature.

Lakartidningen, 2004 Oct 7, 101(41), 3142 - 3, 3146
{Acute otitis media is not treated according to recommendations . Survey of treatment patterns in emergency centers and community health centers}; Ander AL et al.; Usual recommended treatment of acute otitis media (AOM) is antibiotics or expectancy . Different parts of Europe have varying therapy with Holland as an example of more restrictive use of antibiotics . The purpose with this study was to see differences in treatment length, choice of antibiotics, and differences in handling on daytime and emergency hours . 432 case records of children, aged up to ten years were retrospectively investigated . The result shows that antibiotics were prescribed to all except five patients . First choice of antibiotic (70 per cent) was penicillin V that also was more used at emergency hours than daytime at the health centre . Treatment time varied from five to ten days in contrast to national recommendations of five-day therapy . Registrars preferred five-day therapy and specialists seven days . We conclude that penicillin V is first choice of treatment in AOM, that treatment time varies from five to ten days without any underlying reasons and that expectancy was used only in very few cases.

Lin Chuang Er Bi Yan Hou Ke Za Zhi, 2002 Sep, 16(9), 475 - 6
{The curative effect observation of shuanghuanglian and penicillin on acute tonsillitis}; Li W; OBJECTIVE:To investigate the curative effect of shuanghuanglian on acute tonsillitis . METHOD: 95 cases of acute tonsillitis were randomly divided into shuanghuanglian group (treatment group) and penicillin group (control group) . RESULT: The total effective rate in treatment group was 87.5%, hardly less than that (83.0%) in control group (P > 0.05) . CONCLUSION: Shuanghuanglian was an effective medicine in the treatment of acute tonsillitis, in addition, it was effective for virus infection.

Biochem Soc Trans, 2004 Dec, 32(Pt 6), 1051 - 6
Lipids in health and disease; Shepherd J; The evidence linking cholesterol levels in the blood to vascular risk is now incontrovertible and the introduction of HMG CoA (3-hydroxy-3-methylglutaryl coenzyme A) reductase inhibitor (or statin) therapy into clinical practice has now revolutionized the management of lipid disorders and silenced at a stroke the critics of cholesterol control as a means to vascular disease prevention . Statins were the first lipid-lowering agents, which, within a framework of a clinical trial, actually extended life by mechanisms that probably go beyond cholesterol alone . Their benefits are so impressive that some enthusiasts have been emboldened to write that they 'are to atherosclerosis what penicillin was to infectious disease' . But is Nature as easily tamed as we might imagine? Some individuals show a modest or even poor response to statin therapy . The recent discovery of ezetimibe, a highly efficient and precise cholesterol absorption inhibitor, has proven to be a very effective cholesterol lowering alternative for them and combining statins with ezetimibe, thereby inhibiting cholesterol absorption and endogenous synthesis, takes us to realms of cholesterol lowering capability that could not have been dreamt of a decade ago.

J Vet Pharmacol Ther, 2004 Oct, 27(5), 343 - 53
Meta-analysis of pharmacokinetic data of veterinary drugs using the Food Animal Residue Avoidance Databank: oxytetracycline and procaine penicillin G; Craigmill AL et al.; Investigators frequently face the quandary of how to interpret the often times disparate pharmacokinetic parameter values reported in the literature . Combining of data from multiple studies (meta-analysis) is a useful tool in pharmacokinetics . Few studies have explored the use of meta-analysis for veterinary species . Even fewer studies have explored the potential strengths and weaknesses of the various methods of performing a meta-analysis . Therefore, in this study we performed a meta-analysis for oxytetracycline (OTC) and procaine penicillin G (PPG) given intramuscularly to cattle . The analysis included 28 individual data sets from 18 published papers for PPG (288 data points), and 41 individual data sets from 25 published papers for OTC (489 data points) . Three methods were used to calculate the parameters . The first was a simple statistical analysis of the parameter values reported in each paper . The second method was a standard Two-Stage Method (TSM) using the mean concentration vs . time data extracted from each paper . The third method was the use of nonlinear mixed effect modeling (NMEM) of the concentration vs . time data reported in the various papers, treating the mean data as if each set came from an individual animal . The results of this evaluation indicate that all three methods generate comparable mean parameter estimates for OTC and PPG . The only significant difference noted was for OTC absorption half-lives taken from the published literature, a difference attributable to the use of an alternative method of parameter calculation . The NMEM procedure offers the possibility of including covariates such as dose, age, and weight . In this study the covariates did not influence the derived parameters . A combination approach to meta-analysis of published mean data is recommended, where the TSM is the first step, followed by the NMEM approach.

Clin Experiment Ophthalmol, 2004 Oct, 32(5), 526 - 8
Syphilis presenting as scleritis in an HIV-positive man undergoing immune reconstitution; Moloney G et al.; A 45-year-old HIV-positive man receiving highly active antiretroviral therapy (HAART) presented with 6 weeks of right-sided headache and right eye pain . He had been diagnosed seropositive 2 years previously and screened negative for syphilis at that time . Examination demonstrated focal anterior scleritis with underlying retinitis and a mild vitritis . He was found to have positive syphilis serology and further investigations were consistent with neurosyphilis . Parenteral penicillin was commenced with prompt clinical response . This initial presentation of syphilis as acute scleritis emphasizes the need for thorough work-up of immunocompromised patients with inflammatory ocular disease.

Ann Pharmacother, 2004 Dec, 38(12), 2055 - 8 Epub 2004 Oct 19.
Probable sulbactam/ampicillin-associated prolonged cholestasis; Koklu S et al.; OBJECTIVE: To present a single case of sulbactam/ampicillin-induced chronic cholestasis and a literature review of antibiotic-associated chronic cholestasis . CASE SUMMARY: A 74-year-old man with Hodgkin's disease in remission developed severe and prolonged cholestasis after treatment with sulbactam/ampicillin 750 mg twice daily for 7 days . All other etiologies, including Hodgkin's disease, were appropriately ruled out and the cholestasis was ascribed to sulbactam/ampicillin treatment . The patient improved gradually and became asymptomatic 7 months after the last dose of sulbactam/ampicillin . According to the Naranjo probability scale, sulbactam/ampicillin was the probable cause of the cholestasis . DISCUSSION: Ampicillin, a semisynthetic penicillin, has rarely been associated with hepatic injury when used alone . Hepatocellular and acute cholestatic injury due to ampicillin have been described . Cholestasis secondary to sulbactam/ampicillin use has not been previously reported . CONCLUSIONS: Sulbactam/ampicillin, one of the most widely used antibiotics, may cause chronic cholestatic hepatitis . Clinicians should be aware of this adverse affect and consider it during diagnostic workup of liver injury.

Chem Commun (Camb), 2004 Oct 21, (20), 2332 - 3 Epub 2004 Sep 07.
Penicillins as beta-lactamase-dependent prodrugs: enabling role of a vinyl ester exocyclic to the lactam ring; Ruddle CC et al.; Incorporation of a vinyl ester exocyclic to the beta-lactam ring of a penicillin nucleus enables this to act as a beta-lactamase-dependent prodrug - rapid release of the (unactivated) alkoxy component of the vinyl ester is triggered by enzyme-catalysed hydrolysis of the beta-lactam ring, whilst buffer-catalysed hydrolysis of the structure at neutral pH is particularly slow.

J Antimicrob Chemother, 2004 Dec, 54(6), 1155 - 7 Epub 2004 Oct 14.
Is it safe to use carbapenems in patients with a history of allergy to penicillin?
Sodhi M, Axtell SS, Callahan J, Shekar R.
OBJECTIVES: The purpose of this retrospective study was to ascertain the clinical safety of administering carbapenems, namely imipenem/cilastatin and meropenem, in patients with a history of penicillin allergy compared with administering carbapenems in patients with no reported penicillin allergy . Carbapenems are similar in chemical structure to the penicillins and therefore are associated with a risk for allergic cross-hypersensitivity . Carbapenems are commonly avoided in patients with a reported penicillin allergy on the basis of a potential cross-hypersensitivity with penicillin, however, very few studies have been conducted describing the incidence of cross-hypersensitivity between penicillin and carbapenems . METHODS: A retrospective review was conducted in a total of 266 patients who were administered either imipenem/cilastatin or meropenem . The patients were admitted to the Cleveland Clinic Health System-Eastern Region Hospitals during the years 2001 and 2002 . RESULTS: Fifteen of the 163 patients (9.2%) with reported penicillin allergy developed a hypersensitivity reaction to meropenem or imipenem/cilastatin whereas 3.9% of the 103 patients without penicillin allergy developed a hypersensitivity reaction to meropenem or imipenem/cilastatin . These results are not statistically significant . CONCLUSIONS: Based on this study and other similar studies, the true incidence of cross-hypersensitivity reactions between penicillin and carbapenems may be lower than previously reported . Carbapenem use may be reasonable for penicillin allergic patients if caution is exercised.

Expert Rev Anti Infect Ther, 2004 Oct, 2(5), 685 - 93
Telithromycin; Spiers KM et al.; Telithromycin (Ketek), Aventis Pharma), a ketolide, belongs to a new class of antibiotics that was developed for the treatment of upper and lower respiratory tract infections . The prevalence of penicillin and macrolide resistance among respiratory pathogens is increasing in the USA . Telithromycin is highly active against beta-lactam, macrolide and fluoroquinolone reduced-susceptibility pathogens . Its efficacy has been shown to be equal or superior to comparator agents in numerous studies . It has a broad in vitro spectrum versus usual respiratory pathogens and oral once-daily dosing that increases patient compliance . Telithromycin penetrates rapidly into neutrophils in bronchopulmonary tissue, with peak levels obtained in 1 to 2 h . Results of clinical trials show clinical-esponse rates similar to comparator agents . The most frequent adverse events involve the gastrointestinal system, with mild to moderate diarrhea and nausea . A low rate of discontinuation was observed in the studies . Telithromycin is an effective first-line treatment for mild to moderate respiratory infections in adults.

Expert Rev Anti Infect Ther, 2004 Apr, 2(2), 293 - 8
Prevention and treatment of leptospirosis; Edwards CN et al.; Leptospirosis is a common zoonosis acquired by exposure to body fluids, to tissues of infected animals, or to contaminated soil or fresh water . Large outbreaks of leptospirosis have occurred following excess rainfall or in tourists following exposure to fresh water during adventure activities . Prevention may be achieved through the use of protective clothing or by changes in animal husbandry . Immunization is not widely used in human populations but has a role in agriculture . Oral administration of doxycycline (Periostat , CollaGenex) once-weekly can give short-term protection in high-risk environments . The disease in humans has a broad range of symptoms . Treatment may be symptomatic or may require administration of antibiotics, such as doxycycline or penicillin.

Clin Exp Allergy, 2004 Oct, 34(10), 1597 - 601
Self-reported drug allergy in a general adult Portuguese population; Gomes E et al.; AIM: To estimate the prevalence of self-reported drug allergy in adults . METHODS: Cross-sectional survey of a general adult population from Porto (all of whom were living with children involved in the International Study of Asthma and Allergies in Childhood-phase three), during the year 2002, using a self-administered questionnaire . RESULTS: The prevalence of self-reported drug allergy was 7.8% (181/2309): 4.5% to penicillins or other beta-lactams, 1.9% to aspirin or other non-steroidal anti-inflammatory drugs (NSAIDs) and 1.5% to other drugs . In the group 'allergic to beta-lactams', the most frequently implicated drug was penicillin G or V (76.2%) followed by the association of amoxicillin and clavulanic acids (14.3%) . In the group 'allergic to NSAIDs', acetylsalicylic acid (18.2%) and ibuprofen (18.2%) were the most frequently identified drugs, followed by nimesulide and meloxicam . Identification of the exact name of the involved drug was possible in less than one-third of the patients, more often within the NSAID group (59.5%) . Women were significantly more likely to claim a drug allergy than men (10.2% vs . 5.3%) . The most common manifestations were cutaneous (63.5%), followed by cardiovascular symptoms (35.9%) . Most of the reactions were immediate, occurring on the first day of treatment (78.5%) . Only half of the patients were submitted to drug allergy investigations . The majority (86.8%) completely avoided the suspected culprit drug thereafter . CONCLUSIONS: The results showed that self-reported allergy to drugs is highly prevalent and poorly explored . Women seem to be more susceptible . beta-lactams and NSAIDs are the most frequently concerned drugs.

Protein Expr Purif, 2004 Nov, 38(1), 24 - 8
Expression, purification, and characterization of His-tagged penicillin G acylase from Kluyvera citrophila in Escherichia coli; Wen Y et al.; The DNA fragment encoding Kluyvera citrophila penicillin G acylase (KcPGA) was amplified and cloned into the vector pET28b to obtain a C-terminus His-tagged fusion expression plasmid . The fusion protein KcPGA was successfully overexpressed in Escherichia coli BL21(DE3) . The optimal induction concentration of isopropylthio-beta-D-galactoside (IPTG) was found to be 5 microM . The fusion protein was purified in a single step by Ni-IDA affinity chromatograph to a specific activity of 35.3U/mg protein with a final yield of 89% representing a 23-fold purification . The data presented here suggest that the purified fusion protein is stable with respect to pH and temperature . The optimal pH and temperature of recombinant KcPGA are 8.5 and 55 degrees C, respectively . The Km and Vmax are 17.6 microM and 23.8 U/mg, respectively . Therefore, the high yield and high specific activity of recombinant KcPGA produced in E . coli, together with other kinetic parameters, represent an excellent basis for further development of recombinant KcPGA as an immobilized biocatalyst for industrial applications.

Nonlinear Dynamics Psychol Life Sci, 2004 Oct, 8(4), 445 - 78
Information hidden in signals and macromolecules I . Symbolic time-series analysis; Jimenez-Montano MA et al.; We describe the conceptual background and practical implementation of some recently developed techniques for the analysis of symbol sequences and symbolic time series . We emphasize their associated software realization, the WinGramm suite of programs, that includes programs for the calculation of conditional entropies, context-free grammatical complexity, algorithmic distance and redundancy, as well as for the generation of surrogates that preserve symbol pairs and triplets . We demonstrate the usefulness of these programs by means of two illustrative examples, taken from computational neuroscience . In the first one, we obtain evidence of the Markovian character of the cortical inter spike intervals of the rat before penicillin treatment, and its disappearance afterwards . In the second one, we extend previous investigations about neural spike-trains generated by the isolated neuron of the slowly adapting stretch receptor organ (SAO), in order to classify sequences of different length of known neural behaviors . We include new spike trains, digitized employing the optimal partition procedure described by Steuer, Molgedey, Ebeling, & Jimenez-Montano, (2001).

Appl Environ Microbiol, 2004 Oct, 70(10), 6257 - 63
Family shuffling of expandase genes to enhance substrate specificity for penicillin G; Hsu JS et al.; Deacetoxycephalosporin C synthase (expandase) from Streptomyces clavuligerus, encoded by cefE, is an important industrial enzyme for the production of 7-aminodeacetoxycephalosporanic acid from penicillin G . To improve the substrate specificity for penicillin G, eight cefE-homologous genes were directly evolved by using the DNA shuffling technique . After the first round of shuffling and screening, using an Escherichia coli ESS bioassay, four chimeras with higher activity were subjected to a second round . Subsequently, 20 clones were found with significantly enhanced activity . The kinetic parameters of two isolates that lack substrate inhibition showed 8.5- and 118-fold increases in the k(cat)/K(m) ratio compared to the S . clavuligerus expandase . The evolved enzyme with the 118-fold increase is the most active obtained to date anywhere . Our shuffling results also indicate the remarkable plasticity of the expandase, suggesting that more-active chimeras might be achievable with further rounds.

J Bacteriol, 2004 Oct, 186(20), 6768 - 74
FtsZ collaborates with penicillin binding proteins to generate bacterial cell shape in Escherichia coli; Varma A et al.; The mechanisms by which bacteria adopt and maintain individual shapes remain enigmatic . Outstanding questions include why cells are a certain size, length, and width; why they are uniform or irregular; and why some branch while others do not . Previously, we showed that Escherichia coli mutants lacking multiple penicillin binding proteins (PBPs) display extensive morphological diversity . Because defective sites in these cells exhibit the structural and functional characteristics of improperly localized poles, we investigated the connection between cell division and shape . Here we show that under semipermissive conditions the temperature-sensitive FtsZ84 protein produces branched and aberrant cells at a high frequency in mutants lacking PBP 5, and this phenotype is exacerbated by the loss of additional peptidoglycan endopeptidases . Surprisingly, certain ftsZ84 strains lyse at the nonpermissive temperature instead of filamenting, and inhibition of wild-type FtsZ forces some mutants into tightly wound spirillum-like morphologies . The results demonstrate that significant aspects of bacterial shape are dictated by a previously unrecognized relationship between the septation machinery and ostensibly minor peptidoglycan-modifying enzymes and that under certain circumstances improper FtsZ function can destroy the structural integrity of the cell.

Clin Neurophysiol, 2004 Nov, 115(11), 2502 - 10
Detection of abnormal cerebral excitability by coincident stimulation and recording; Hentall ID; OBJECTIVE: A method for mapping brain excitability and detecting abnormalities, by concurrently stimulating and recording 'focal' compound responses through one microelectrode, was evaluated in three rat epilepsy models in comparison with distal stimulation of perforant path afferents . METHODS: A fixed trajectory from neocortex to dentate gyrus was mapped under halothane anesthesia . Several weeks earlier, tetanus toxin or vehicle was microinjected into the dentate polymorphic layer, or else rats were genetically epilepsy-prone (GEPR-9) or epilepsy-resistant (GERR-0) . Other (unmapped) rats received acute penicillin microinjections within the dentate granular layer . RESULTS: Focal responses, although widespread, proved largest in the dentate (>+/-0.5 mV) . Tetanus toxin diminished focal responses near the microinjection site versus vehicle-microinjected (66%) or contralateral controls (55%), but enhanced them elsewhere in the dentate . It enhanced distal responses at all hippocampal locations . Focal but not distal responses were higher in GEPR-9 than in GERR-0 rats at widespread forebrain locations (mean 233%) . Penicillin facilitated both focal and distal dentate responses, but the focal facilitation peaked sooner (about 75 versus 180 min) . CONCLUSIONS: Focal responses better uncover pervasive or discrete excitability differences . SIGNIFICANCE: Focal mapping may aid in diagnostic imaging and intraoperative targeting, offering high resolution, rapid performance, low stimulus currents and minimal invasion.

Lancet, 2004 Sep 25, 364(9440), 1141 - 8
Oral amoxicillin versus injectable penicillin for severe pneumonia in children aged 3 to 59 months: a randomised multicentre equivalency study; Addo-Yobo E et al.; BACKGROUND: Injectable penicillin is the recommended treatment for WHO-defined severe pneumonia (lower chest indrawing) . If oral amoxicillin proves equally effective, it could reduce referral, admission, and treatment costs . We aimed to determine whether oral amoxicillin and parenteral penicillin were equivalent in the treatment of severe pneumonia in children aged 3-59 months . METHODS: This multicentre, randomised, open-label equivalency study was undertaken at tertiary-care centres in eight developing countries in Africa, Asia, and South America . Children aged 3-59 months with severe pneumonia were admitted for 48 h and, if symptoms improved, were discharged with a 5-day course of oral amoxicillin . 1702 children were randomly allocated to receive either oral amoxicillin (n=857) or parenteral penicillin (n=845) for 48 h . Follow-up assessments were done at 5 and 14 days after enrollment . Primary outcome was treatment failure (persistence of lower chest indrawing or new danger signs) at 48 h . Analyses were by intention-to-treat and per protocol . FINDINGS: Treatment failure was 19% in each group (161 patients, pencillin; 167 amoxillin; risk difference -0.4%; 95% CI -4.2 to 3.3) at 48 h . Infancy (age 3-11 months; odds ratio 2.72, 95% CI 1.95 to 3.79), very fast breathing (1.94, 1.42 to 2.65), and hypoxia (1.95, 1.34 to 2.82) at baseline predicted treatment failure by multivariate analysis . INTERPRETATION: Injectable penicillin and oral amoxicillin are equivalent for severe pneumonia treatment in controlled settings . Potential benefits of oral treatment include decreases in (1) risk of needle-borne infections; (2) need for referral or admission; (3) administration costs; and (4) costs to the family.

Hautarzt, 2004 Nov, 55(11), 1087 - 9
{Current opinions in syphilis therapy and serological follow-up . Commentary on the article by M . Hartmann in Hautarzt, issue 2 (2004)}; Heise H; Penicillin is currently the drug of choice for therapy of syphilis . Clemizole and procaine penicillin are no longer available . For this reason only benzathine penicillin and infusion therapy with benzyl penicillin are possible . Treatment with doxycyline or ceftriaxone is also conceivable . Suitable serological methods are necessary to control the safety of the therapy.

Indian J Pediatr, 2004 Sep, 71(9), 789 - 93
Sickle cell disease in central India; Patel AB et al.; OBJECTIVE: The incidence and the risk factors of sickle cell disease (SCD), vaccinated with Pneumococcal vaccine and on penicillin prophylaxis has not been previously reported in India . METHODS: This prospective hospital based study followed 325 children on penicillin prophylaxis, of which 161 were vaccinated for pneumococci, over 146.84 person years to determine the incidence and determinants of crisis (SCC) and infections . The average age at presentation was 7.05 +/- 3.26 years with male preponderance below 2 years . RESULTS: The main causes for hospitalizations were for blood transfusion, SCC and infections . The incidence of SCC was 1.25 per patient per year and that of infection was 1.38 per person per year . The risk factors for SCC were Mahar caste (p = 0.007) non-compliance (p = 0.000) and protein energy malnutrition (PEM) (p = 0.0015) and for infection were also PEM (p = 0.023), Mahar caste (p = 0.021) and noncompliance (p = 0.001) . CONCLUSION: Malnutrition and non-compliance with medication increased the patient's susceptibility to SCC and infections.

J Hist Med Allied Sci, 2004 Oct, 59(4), 555 - 87
Changing interest among physicians toward pneumococcal vaccination throughout the twentieth century; Kazanjian P; Interest in using pneumococcal vaccination among physicians has come full circle since the early twentieth century . Interest first arose during an epidemic among South African gold miners when a potential therapeutic agent, ethylhydrocupreine, caused significant toxicities . When a safe and effective vaccine became available in 1946, interest in using it paradoxically waned as its introduction coincided with the advent of penicillin . Physicians believed that this effective new antibiotic would change pneumonia from a dreaded infection to a casual, infrequent occurrence . The manufacturer was unable to promote vaccine use and withdrew it from the market . Enthusiasm for vaccination remained low long after limitations in antibiotic therapy of pneumococcal infections became clear in the 1960s and a new vaccine once again became available in 1978 . Interest in vaccination was eventually renewed in the 1990s when the propagation of pneumococcal resistance to multiple agents diminished the complete confidence that physicians had in antibiotics and when populations at risk for infection were expanding . Scientific evidence of vaccine efficacy, demonstrated in 1944 and 1977, has not alone been sufficient to convince physicians to use vaccination . Rather, doctors have accepted the need to vaccinate for pneumococcus when they have recognized the shortcomings of therapeutic measures during epidemic periods.

Acupunct Electrother Res, 2004, 29(1-2), 43 - 51
The effects of ear-point stimulation on the contents of somatostatin and Amino acid neurotransmitters in brain of rat with experimental seizure; Shu J et al.; The goal of this study was to elucidate the anti-convulsion mechanisms of ear-point stimulation in rat with experimental seizure . We prepared the epilepsy rats by intrahippocampal injection of penicillin . One hour later the lower 1/2 auricular lobules of seizure rats, containing ear-points Pizhixia and Shenmen etc., was electrically stimulated, which was imitated as ear-point electrical acupuncture in humans . Radioimmunoassay and biochemical techniques were used to determine the contents of somatostatin and amino acid neurotransmitters in hippocampus of rats . The outcomes revealed epileptiform behaviors of rat were appeared after penicillin-injected . The contents of somatostatin, aspartic acid, glutamine and GABA were increased . When these rats were subsequently given the ear-point electrical stimulation, the convulsion behaviors were definitely improved . At the same time the contents of the somatostatin, aspartic acid and glutamine in hippocampus of seizure rat were significantly decreased correspondingly . The contents of glycine, taurine and GABA had increased . Based on the results above, it was suggestive that ear-point electrical stimulation had anti-epilepsy effects, which might be involved in the decreases of the contents of the somatostatin, aspartic acid and glutamine, and increases of the contents of glycine, taurine and GABA in hippocampus of seizure rat.

J Mol Biol, 2004 Oct 8, 343(1), 157 - 71
Conformational flexibility of the C terminus with implications for substrate binding and catalysis revealed in a new crystal form of deacetoxycephalosporin C synthase; Oster LM et al.; Deacetoxycephalosporin C synthase (DAOCS) from Streptomyces clavuligerus catalyses the oxidative ring expansion of the penicillin nucleus into the nucleus of cephalosporins . The reaction requires dioxygen and 2-oxoglutarate as co-substrates to create a reactive iron-oxygen intermediate from a ferrous iron in the active site . The active enzyme is monomeric in solution . The structure of DAOCS was determined earlier from merohedrally twinned crystals where the last four C-terminal residues (308-311) of one molecule penetrate the active site of a neighbouring molecule, creating a cyclic trimeric structure in the crystal . Shortening the polypeptide chain from the C terminus by more than four residues diminishes activity . Here, we describe a new crystal form of DAOCS in which trimer formation is broken and the C-terminal arm is free . These crystals show no signs of twinning, and were obtained from DAOCS labelled with an N-terminal His-tag . The modified DAOCS is catalytically active . The free C-terminal arm protrudes into the solvent, and the C-terminal domain (residues 268-299) is rotated by about 16 degrees towards the active site . The last 12 residues (300-311) are disordered . Structures for various enzyme-substrate and enzyme-product complexes in the new crystal form confirm overlapping binding sites for penicillin and 2-oxoglutarate . The results support the notion that 2-oxoglutarate and dioxygen need to react first to produce an oxidizing iron species, followed by reaction with the penicillin substrate . The position of the penicillin nucleus is topologically similar in the two crystal forms, but the penicillin side-chain in the new non-twinned crystals overlaps with the position of residues 304-306 of the C-terminal arm in the twinned crystals . An analysis of the interactions between the C-terminal region and residues in the active site indicates that DAOCS could also accept polypeptide chains as ligands, and these could bind near the iron.

Biochemistry, 2004 Sep 28, 43(38), 12375 - 81
Expression and characterization of the isolated glycosyltransferase module of Escherichia coli PBP1b; Barrett DS et al.; The enzymes involved in the biosynthesis of peptidoglycan are targets for the development of new antibiotics . The bifunctional high molecular weight (HMW) penicillin-binding proteins (PBPs), which contain both glycosyltransferase (GTase) and transpeptidase (TPase) activities, are particularly attractive targets because of their extracellular location . However, there is limited mechanistic or structural information about the GTase modules of these enzymes . In this paper, we describe the overexpression and characterization of the GTase module of Escherichia coli PBP1b, a paradigm of the HMW PBPs . We define the C-terminal boundary of the GTase module and show that the isolated module can be overexpressed at significantly higher levels than the full-length protein . The catalytic efficiency and other characteristics of the isolated module are comparable in most respects to the full-length enzyme . This work lays the groundwork for mechanistic and structural analysis of GTase modules.

Immunohematol, 2002 Jun, 18(2), 27 - 32
ractical aspects of investigating drug-induced immune hemolytic anemia due to cefotetan or ceftriaxone-a case study approach; Arndt PA; In the 1970s, the most common causes of drug-induced immune hemolytic anemia were methyldopa and penicillin . Since 1990, the most common causes of drug-induced immune hemolytic anemia have been the second- and third-generation cephalosporins, cefotetan and ceftriaxone . Three case histories illustrate the common findings in the serologic investigation of immune hemolytic anemias due to these two drugs . Immunohematology 2002;18:27-32.

MMW Fortschr Med, 2004 Apr 26, 146 Spec No 1, 39 - 41
{Syphilis--diagnosis, treatment and peculiarities in HIV-infected patients}; Hartmann M et al.; Venereal syphilis is a chronic cyclic infectious disease that, if untreated, runs a decades-long course . The responsible pathogen is Treponema pallidum . Clinically, a differentiation is made into early (primary) syphilis (up to 1 year following infection, syphilis I), during which disease manifestations are localized, secondary syphilis (syphilis II) with generalized manifestations, and late, or tertiary syphilis (syphilis III) . Clinical manifestations that have been observed in HIV patients are syphilis maligna and neurosyphilis . Treatment of choice continues to be penicillin . Instead of only a single injection of penicillin, HIV infected patients with early syphilis should be given three injections, with an interval of 1 week between them, to prevent the development of neurosyphilis.

Ceska Slov Farm, 2004 Jul, 53(4), 159 - 64
{Pharmacological aspects of Lyme borreliosis}; Dvorakova J et al.; Clinical signs of Lyme boreliosis in humans are versatile and in their whole scope they finally affect the nervous system, heart, and joints . The therapeutic effect of antibiotics is maximal in the first acute stage of the disease when doxycycline and amoxiciline are administered . These antibiotics possess a comparable in vitro effect, tissue penetration, pharmacokinetics, and therapeutic effect . The treatment of disseminated infections in the second stage, such as neuroborreliosis, carditis, and iritis, is difficult and with relative success they are treated with large doses of penicillin G, or cefriaxon, and doxycycline . The treatment of the third stage of borreliosis aims at chronic inflammatory changes in the affected organs . Antibiotics, however, are successfully effective only in 50% of cases . Administration of antibiotics, such as tetracycline, cefuroxim, doxycycline, or large doses of penicillin is a long-term one, coming up to four weeks . A special therapeutic regimen is used in pregnant women and children.

Int Urol Nephrol, 2004, 36(2), 159 - 61
Eosinophilic cystitis induced by penicillin; Tsakiri A et al.; A 30-year-old woman developed classic symptoms of painful bladder disease and eosinophilic cystitis as an adverse effect of penicillin for abdominal actinomycosis . The symptoms were reversible after stopping penicillin.

J Vet Sci, 2004 Sep, 5(3), 247 - 51
Thickness of cumulus cell layer is a significant factor in meiotic competence of buffalo oocytes; Warriach HM et al.; This study evaluated the meiotic competence of buffalo oocytes with different layers of cumulus cells . A total of 588 oocytes were collected from 775 ovaries averaging 0.78 oocytes per ovary . Oocytes with homogenous cytoplasm (n = 441) were selected for in vitro maturation (IVM) and divided into four groups based on their cumulus morphology: a) oocytes with > or = = 3 layers of cumulus cells, b) 1-2 layers of cumulus cells and oocytes with partial remnants or no cumulus cells to be cocultured c) with or d) without cumulus cells . Oocytes in all four groups were matured in 100 microL drop of TCM-199 supplemented with 10 microg/mL follicle stimulating hormone (FSH), 10 microg/mL luteinizing hormone (LH), 1.5 microg/mL estradiol, 75 microg/mL streptomycin, 100 IU/mL penicillin, 10 mM Hepes and 10% FBS at 39 degrees C and 5% CO2 for 24 hours . After IVM, cumulus cells were removed from oocytes using 3 mg/mL hyaluronidase, fixed in 3% glutaraldehyde, stained with DAPI and evaluated for meiotic competence . The oocytes with > or = 3 layers of cumulus cells showed higher maturation rates (p<0.05: 64.5%) than oocytes with partial or no cumulus cells (8.6%) and oocytes co-cultured with cumulus cells (34.5%) but did not differ from oocytes having 1-2 layers of cumulus cells (51.4%) . The degeneration rates were higher (p<0.05) for oocytes with partial or no cumulus cells (51%) than rest of the groups (range: 13.8% to 17.4%) . These results suggest that buffalo oocytes with intact layers of cumulus cells show better IVM rates than oocytes without cumulus cells and the co-culture of poor quality oocytes with cumulus cells improves their meiotic competence.

Ment Retard Dev Disabil Res Rev, 2004, 10(2), 117 - 21
Sleep and arousal mechanisms in experimental epilepsy: epileptic components of NREM and antiepileptic components of REM sleep; Shouse MN et al.; Neural generators related to different sleep components have different effects on seizure discharge . These sleep-related systems can provoke seizure discharge propagation during nonrapid eye movement (NREM) sleep and can suppress propagation during REM sleep . Experimental manipulations of discrete physiological components were conducted in feline epilepsy models, mostly in the systemic penicillin epilepsy model of primary generalized epilepsy and the amygdala kindling model of the localization-related seizure disorder, temporal lobe epilepsy . The sleep-wake state distribution of seizures was quantified before and after discrete lesions, systemic and localized drug administration, and/or photic stimulation, as well as in relation to microdialysis of norepinephrine . We found that (1) neural generators of synchronous EEG oscillations--including tonic background slow waves and phasic "arousal" events (sleep EEG transients such as sleep spindles and k-complexes)--combine to promote electrographic seizure propagation during NREM and drowsiness, and antigravity muscle tone permits seizure-related movement; (2) neural generators of asynchronous neuronal discharge patterns reduce electrographic seizures during alert waking and REM sleep, and skeletal motor paralysis blocks seizure-related movement during REM; (3) there are a number of similarities between amygdala-kindled kittens and children with Landau-Kleffner Syndrome (LKS) that suggest a link among seizures, sleep disorders, and behavioral abnormalities/regression.

Aust Vet J, 2004 Aug, 82(8), 479 - 80
Nonfatal splenic haematoma and pancytopenia in an ass; Ayala I et al.; This report describes a case of nonfatal idiopathic splenic haematoma and pancytopenia in a female ass, a condition that has not been previously reported in this species . A 12-year-old female ass weighing 225 kg was presented with signs of anorexia, depression and prominent abdominal distension . At the onset of clinical signs there was evidence of anaemia, leucopenia and thrombocytopenia . A large mass was palpated per rectum . The mass was confluent with the spleen and extended across the entire width of the abdomen . Percutaneous transabdominal ultrasonography and laparoscopy under general anaesthesia confirmed the diagnosis of splenic haematoma . The ass was treated initially with intravenous polyionic fluids; vitamins, trace elements and aminoacids; clanobutin; and penicillin and gentamicin, and was transfused with whole blood . After 5 days of hospitalisation the ass appeared brighter, and after 10 days the animal was discharged to recuperate at pasture . Six months later the animal's demeanour and appetite had improved . Repeat ultrasonographic examination showed persistence of the mass, but its thickness had decreased by 2 to 3 cm . A small mineralised area suggesting organisation of the haematoma was also detected . The haematological parameters had returned to normal values and the ass was clinically normal.

Clin Microbiol Infect, 2004 Sep, 10(9), 777 - 84
Beta-lactamase-producing bacteria in mixed infections; Brook I; Beta-lactamase-producing bacteria (BLPB) can play an important role in polymicrobial infections . They can have a direct pathogenic impact in causing infections, as well as an indirect effect through their ability to produce the beta-lactamase . BLPB may not only survive penicillin therapy themselves, but can also protect other penicillin-susceptible bacteria from penicillin by releasing free beta-lactamase into their immediate environment . This phenomenon occurs in upper respiratory tract, skin, soft tissue, surgical and other infections . The in-vitro and in-vivo clinical evidence supporting the role of BLPB in the increasing failure of penicillin to resolve such infections, and the implications of this phenomenon for the management of infections, are discussed.

Proteomics, 2004 Sep, 4(9), 2602 - 7
Determination of protein-protein interactions through aldehyde-dextran intermolecular cross-linking; Fuentes M et al.; A very simple strategy, based on the intermolecular cross-linking of associated proteins by using aldehyde-dextrans, has been proposed to detect protein-protein interactions . Aldehyde-dextran was able to cross-link different enzymes composed of several polypeptide chains (e.g., trypsin and penicillin G acylase), proteolyzated proteins (e.g., extracts from porcine pancreas) and finally, an immunocomplex (horseradish peroxidase/anti-horseradish peroxidase) . This cross-linked immunocomplex could be selectively adsorbed on immobilized anti-rabbit IgG . The presence of unspecific covalent attachment between unrelated protein molecules was not detected . Thus, this strategy permits the cross-linking of different protein components and avoids the formation of nonspecific protein-protein associations.

J Perinat Med, 2004, 32(4), 375 - 7
Maternal anaphylaxis and fetal brain damage after intrapartum chemoprophylaxis; Berardi A et al.; We report a case of maternal anaphylaxis following intrapartum chemoprophylaxis . The term fetus developed severe brain damage as a consequence of intrapartum asphyxia . The lesions resulted from maternal hypotension following anaphylaxis . We discuss the feto-maternal risks and the controversial treatment of such a condition . The increasing number of penicillin-treated parturients will result in further cases of maternal anaphylaxis than previously found.

J Bacteriol, 2004 Sep, 186(18), 6110 - 7
Structural determinants required to target penicillin-binding protein 3 to the septum of Escherichia coli; Piette A et al.; In Escherichia coli, cell division is mediated by the concerted action of about 12 proteins that assemble at the division site to presumably form a complex called the divisome . Among these essential division proteins, the multimodular class B penicillin-binding protein 3 (PBP3), which is specifically involved in septal peptidoglycan synthesis, consists of a short intracellular M1-R23 peptide fused to a F24-L39 membrane anchor that is linked via a G40-S70 peptide to an R71-I236 noncatalytic module itself linked to a D237-V577 catalytic penicillin-binding module . On the basis of localization analyses of PBP3 mutants fused to green fluorescent protein by fluorescence microscopy, it appears that the first 56 amino acid residues of PBP3 containing the membrane anchor and the G40-E56 peptide contain the structural determinants required to target the protein to the cell division site and that none of the putative protein interaction sites present in the noncatalytic module are essential for the positioning of the protein to the division site . Based on the effects of increasing production of FtsQ or FtsW on the division of cells expressing PBP3 mutants, it is suggested that these proteins could interact . We postulate that FtsQ could play a role in regulating the assembly of these division proteins at the division site and the activity of the peptidoglycan assembly machineries within the divisome.

Bacteriol Virusol Parazitol Epidemiol, 2003 Apr-Sep, 48(2-3), 165 - 8
{Leptospirosis--epidemic, clinical and diagnostic aspects}; Sipos A et al.; Leptospirosis is a major public health problem throughout the world . We studied 22 cases of leptospirosis . They were hospitalised between 1999-2003 . Men were more affected than women and those with rural origin prevailed, too . The direct infection was more often found in these cases . These patients presented a large spectrum of signs and symptoms attributable to this spirochetal pathogen . The etiology was dominated by L . pomona, L . canicola, L . wolffi . Leptospirosis presented with 3 syndromes: Weil's syndrome, atypical pneumonia syndrome and aseptic meningitis . The adequate treatment was with penicillin or ampicillin i.v.

Protein Eng Des Sel, 2004 Jul, 17(7), 571 - 9 Epub 2004 Aug 27.
Increasing the synthetic performance of penicillin acylase PAS2 by structure-inspired semi-random mutagenesis; Gabor EM et al.; A semi-random mutagenesis approach was followed to increase the performance of penicillin acylase PAS2 in the kinetically controlled synthesis of ampicillin from 6-aminopenicillanic acid (6-APA) and activated D-phenylglycine derivatives . We directed changes in amino acid residues to positions close to the active site that are expected to affect the catalytic performance of penicillin acylase: alpha R160, alpha F161 and beta F24 . From the resulting triple mutant gene bank, six improved PAS2 mutants were recovered by screening only 700 active mutants with an HPLC-based screening method . A detailed kinetic analysis of the three most promising mutants, T23, TM33 and TM38, is presented . These mutants allowed the accumulation of ampicillin at 4-5 times higher concentrations than the wild-type enzyme, using D-phenylglycine methyl ester as the acyl donor . At the same time, the loss of activated acyl donor due to the competitive hydrolytic side reactions could be reduced to <20% with the mutant enzymes compared >80% wild-type PAS2 . Although catalytic activity dropped by a factor of 5-10, the enhanced synthetic performance of the recovered penicillin acylase variants makes them interesting biocatalysts for the production of beta-lactam antibiotics.

Indian J Exp Biol, 2003 Nov, 41(11), 1279 - 84
Central inhibitory effect of Moringa oleifera root extract: possible role of neurotransmitters; Ray K et al.; Effect of chronic treatment of standardized aqueous extract of Moringa oleifera (MO) root (100, 200, 300, 350, 400, 450 mg/kg; po) on penicillin (PCN) induced convulsion, locomotor behaviour, brain serotonin (5-HTT), dopamine (DA) and norepinephrine (NE) level was studied in Holtzman strain adult albino rats . The result revealed that pretreatment with MO inhibited PCN-induced seizure and markedly reduced locomotor activity . Chronic treatment with MO significantly increased the 5-HT and decreased the DA level in cerebral cortex (CC), midbrain (MB), caudate nucleus (CN) and cerebellum (CB) . NE level was significantly decreased in CC but no appreciable change was observed in MB, CB and CN . Thus the central inhibitory effect of MO is discussed in the light of the disturbed balance between 5-HT, DA and NE.

Genes Cells, 2004 Sep, 9(9), 765 - 71
FtsZ-dependent localization of GroEL protein at possible division sites; Ogino H et al.; When Escherichia coli is treated with penicillin, the envelopes bulge at the centre of the cells and the cells then lyse . The bulges expand into vesicle-like structures termed penicillin-induced vesicles . We have developed a method to isolate these structures and have shown that they contain mainly membrane proteins plus a high concentration of a 60 kDa protein . The N-terminal amino acid sequence of the protein is identical to that of GroEL protein . Western blotting analysis using anti-GroEL antibody showed that GroEL is indeed concentrated in the vesicles . Indirect immuno-fluorescence microscopy showed that GroEL protein is localized at the centre of the cells at the site of formation of FtsZ-rings . Localization of GroEL is dependent on FtsZ but not other Fts proteins . GroEL mutants formed elongated cells having no or asymmetrically localized FtsZ-rings at the restrictive temperature . These findings suggest a possible role of the GroEL protein in cell division.

Headache, 2004 Sep, 44(8), 806 - 11
Tolosa-Hunt syndrome due to actinomycosis of the cavernous sinus: the infectious hypothesis revisited; Mandrioli J et al.; BACKGROUND: The Tolosa-Hunt syndrome is characterized by ophthalmoplegia with unilateral severe retro-orbital pain associated to a granulomatous inflammatory process occupying the cavernous sinus or the superior orbital fissure . The etiology is unknown and diagnosis is based upon a clinical response to steroid treatment and exclusion of neoplasm, trauma, aneurysms, infectious, and inflammatory diseases . CASE DESCRIPTION: A 43-year-old man was admitted because of a 1-week history of acute onset left-sided retro-orbital pain, followed by left sixth cranial nerve palsy . Magnetic resonance imaging was normal and Tolosa-Hunt syndrome was suspected . Steroid treatment controlled pain with recovery of ophthalmoplegia . Four months later, when a good response to treatment was still present, brain magnetic resonance imaging revealed a lesion enlarging the left cavernous sinus, isointense with the gray matter on T1-weighted sequences, hypointense on T2-weighted images, and with homogeneous enhancement after gadolinium injection . Two months later, ocular pain and sixth cranial nerve palsy recurred and new brain magnetic resonance imaging showed an extension of the tissue occupying the left cavernous sinus, over the sella, to the right cavernous sinus, making possible an endoscopic transphenoidal biopsy . RESULTS: Histopathological study revealed a granulomatous aspecific inflammation containing actinomycetes colonies . The patient was treated with intravenous penicillin G followed by amoxicillin per os, with improvement of pain and ophthalmoplegia . A control magnetic resonance imaging 1 month after therapy showed a consistent reduction of the enlarged cavernous sinus, and 3 months later neurological examination and brain magnetic resonance imaging were completely normal . CONCLUSIONS: The present case suggests that the International Classification of Headache Disorders (2nd edition) definition of Tolosa-Hunt syndrome does not reflect the complexity of the syndrome and that some cases of secondary painful ophthalmoplegias can fit the criteria for the primary form . Since the biopsy can only rarely be performed, we agree with other authors that clinical and radiological follow-up should be performed for at least 2 years . Moreover, we propose that in patients with painful ophthalmoplegia having transient response to steroid therapy, a trial with antibiotic therapy should be taken into account.

Ginecol Obstet Mex, 2004 Apr, 72, 162 - 5
{Tuboovaric actinomycosis . A report of a case}; Mejia Salazar YR et al.; OBJECTIVE: Tuboovaric actinomycosis case report . PRESENTATION: Patient: eighteen-year-old woman using intrauterine devise for the past two years and with a four months old appendicectomy . Initially, a two month old pelvic tumor with acute abdominal pain and fever was identified . A laparotomy was performed with total pelvic tumor section . A week later, postoperatory colonskin fistula appeared requiring surgery . The histopathology report showed tuboovaric actinomycosis . Therefore, sodic penicillin was used to treat the patient until health was recovered . CONCLUSION: Actinomycosis is characterized by late diagnosis and must be suspected in patients with pelvic tumor exeresis with nonsatisfactory evolution, where intestinal surgery and IUD use are risk factors.

Allergy Asthma Proc, 2004 May-Jun, 25(3), 165 - 8
Preparation of benzylpenicilloyl-polylysine: a preliminary study; Vemuri P et al.; The manufacturing of PrePen (benzylpenicilloyl-polylysine) was suspended from September 2000 through November 2001 because of Food and Drug Administration intervention . PrePen is penicilloyl bound to polylysine and is considered to be the major determinant of penicillin metabolism; it is used as a skin-testing reagent to detect immunoglobulin E antibodies in people with a history of penicillin allergy . Because of the uncertainty of whether PrePen would be made available in the future, we attempted to make benzylpenicilloyl-polylysine in our laboratory using a modification of a previously described method . Subsequently, we compared our preparation with PrePen by enzyme-linked immunosorbent assay and skin testing . Using a patient previously documented to have a positive reaction to PrePen by history and intradermal skin testing, a puncture test to PrePen as well as dilutions of benzylpenicilloyl-polylysine was negative . Positive intradermal tests were performed on PrePen and benzylpenicilloyl-polylysine at 5 mg/mL . The enzyme-linked immunosorbent assay was performed to compare the antigenicity of PrePen and benzylpenicilloyl-polylysine and revealed similar binding to both . Subsequently, cutaneous testing on 10 additional penicillin-allergic people was performed, with corroborative results . Our benzylpenicilloyl-polylysine production methodology could prove useful to those who do not have access to PrePen or another similar reagent.

Allergy Asthma Proc, 2004 May-Jun, 25(3), 157 - 60
Penicillin hypersensitivity: value of clinical history and skin testing in daily practice; Kalogeromitros D et al.; Penicillin often is excluded as a treatment option based on patients' self-reported history of an adverse reaction to penicillin . The objective of this prospective study was to determine the likelihood of true penicillin allergy in patients with vague and convincing histories of penicillin allergy and to evaluate the diagnostic value added by appropriate skin testing . Six hundred thirty-eight patients with prior beta-lactam intake had a current indication for penicillin therapy and were referred for testing with the major (benzylpenicilloyl polylysine) and minor (minor determinant mixture) penicillin determinants from the inpatient and outpatient service of Athens University Dermatological hospital from January 2000 to December 2002 . The prevalence of positive skin tests in the total group and in those patients with vague and convincing histories of penicillin allergy was determined . Positive skin tests were observed in 19/638 (3%) of the total group, 5 out of 542 (0.9%) patients without any history of penicillin allergy, 14 out of 96 (14.6%) patients with vague history (confidence interval {CI} 95% = 5.95-59.92), and 13 out of 18 (72.2%) patients with a convincing history of type I hypersensitivity reaction (chi2 = 286.3: odds ratio = 281.3: CI 95% = 62.19-1440.8) . Patients with a vague history of penicillin allergy are 18 times more likely to have a positive penicillin skin test, and a convincing reaction history increases the likelihood by 281-fold compared with patients without a history of penicillin allergy . However, the fact that 5 of 18 (27.8%) patients with a convincing history were negative when skin tested points out that skin testing is helpful if the need for penicillin administration is compelling.

Orthopedics, 2004 Jul, 27(7), 719 - 20
Is this patient penicillin-allergic?
Sheth A, Smith KM.
Increased claims of hypersensitivity reactions are being reported due to the inability to differentiate between the terms "allergic reaction" and "adverse effect."

Brain Res, 2004 Sep 10, 1020(1-2), 214 - 9
Inhibition of nociceptin/orphanin FQ on penicillin-induced seizures in rats; Feng Y et al.; The opioid peptides were thought to be involved in specific types of seizures . Nociceptin/Orphanin FQ (NC) is the endogenous ligand of the nociceptin opioid peptide (NOP) receptor and may play a role in epilepsy . However, accumulated evidences indicated that NC had both anti- and pro-convulsive effects, and the direct effect of NC in modulating epilepsy in the hippocampus still remained unclear . In this study, we investigated the effect of NC on penicillin-induced seizures (PIS) in rats . Seizure model was produced by intra-hippocampus injection of penicillin in anesthetized rats . The electroencephalography (EEG) was then observed and estimated by power spectrum analysis . Pretreatment of NC (intracerebroventricular, i.c.v.) depressed PIS in a dose-dependent manner at doses of 0.055, 0.55 and 5.5 nmol in 2 microl saline, respectively . {Nphe1}Nociceptin(1-13)NH2, a selective NOP receptor antagonist reversed the effect of NC against PIS, and this antagonist was inactive to PIS itself . These results indicated that NC had a receptor-specific preventive effect against PIS.

Pediatr Int, 2004 Aug, 46(4), 415 - 8
Investigation of DNA damage in lymphocytes exposed to benzathine penicillin G; Koseoglu V et al.; BACKGROUND: Benzathine penicillin G (BPG) is a widely used antibiotic for treatment or prophylaxis of certain infectious diseases . Previous in vivo studies using sister chromatid exchange (SCE) frequency and comet assay, had showed that long-term administration of benzathine penicillin G may cause some degree of DNA damage in children with rheumatic fever . METHODS: Because DNA damage has also been reported in various connective tissue disorders, to rule out the possible effects of underlying disease on DNA integrity, 3-day-cultured lymphocytes obtained from nine healthy individuals were exposed to BPG at different concentrations (0.002, 0.02 and 0.1 micro g/mL), and sister chromatid exchange frequencies were studied . The mean SCE frequency per metaphase was calculated from 20 selected cells for each individual . RESULTS: The incidence of SCE frequency did not differ when all groups were compared . Comparing between each concentration group, exposure to BPG did not cause a dose-dependent increase in SCE frequency (Student's t-test, P > 0.05) . CONCLUSION: Insignificant changes (P > 0.05) in SCE, within the 3-day exposure to BPG, may suggest that DNA damage did not occur . Short-term exposure to BPG does not have toxic effects on DNA . In contrast, this preliminary study should be supported by other genotoxicity assays, expanding the exposure time to longer periods, in order to exclude rapid DNA repair mechanisms . and a possible role of underlying disease on DNA integrity should not be ignored.

Amino Acids, 2004 Aug, 27(1), 101 - 5 Epub 2004 Mar 16.
Total enzymatic synthesis of cholecystokinin CCK-5; Xiang H et al.; This paper describes the enzymatic synthesis of the C-terminal fragment H-Gly-Trp-Met-Asp-Phe-NH2 of cholecystokinin . Immobilized enzymes were used for the formation of all peptide bonds except thermolysin . Beginning the synthesis with phenylacetyl (PhAc) glycine carboxamidomethyl ester (OCam) and H-Trp-OMe by using immobilized papain as biocatalyst in buffered ethyl acetate, the dipeptide methyl ester was then coupled directly with Met-OEt.HCl by alpha-chymotrypsin/Celite 545 in a solvent free system . For the 3+2 coupling PhAc-Gly-Trp-Met-OEt had to be converted into its OCam ester . The other fragment H-Asp(OMe)-Phe-NH2 resulted from the coupling of Cbo-Asp(OMe)-OH with H-Phe-NH2.HCl and thermolysin as catalyst, followed by catalytic hydrogenation . Finally PhAc-Gly-Trp-Met-Asp-Phe-NH2 was obtained in a smooth reaction from PhAc-Gly-Trp-Met-OCam and H-Asp(OMe)-Phe-NH2 with alpha-chymotrypsin/Celite 545 in acetonitrile, followed by basic hydrolysis of the beta-methyl ester . The PhAc-group is removed with penicillin G amidase and CCK-5 is obtained in an overall isolated yield of 19.6%.

Int J Cardiol, 2004 Sep, 96(3), 483 - 4
Sydenham's chorea-clinical characteristics of nine patients; Davutoglu V et al.; Sydenham's chorea is still the most frequently seen form of acquired chorea in childhood in developing countries . Nine patients presented with Sydenham's chorea as one of the major criteria (one or more attacks) were evaluated their clinical characteristics and treatment . All patient were given sodium valproate . Clinical improvement began 11+/-4.0 days in sodium valproate treatment, and no adverse effect was seen due to the drugs . Echocardiography revealed rheumatic carditis sequela in all patient . The nine Sydenham's chorea patients presented 13 attacks of chorea in follow-up . We observed isolated chorea in 44% of patients, and 22% presented one or more recurrences . The interval between the attacks ranged from months to 2 years . The 90% of the patients were not on prophylaxis with benzathine penicillin . One patient had diagnosis of obsessive-compulsive disorder, and one had diagnosis of attention deficit hyperactivity disorder in the follow-up period . This report emphasizes the significance of Sydenham's chorea and sequela of rheumatic carditis association and a high risk of developing neuropsychiatric disorders in the follow-up period . Valproic acid is an effective and safe drug in the treatment of Sydenham's chorea.

Acta Crystallogr D Biol Crystallogr, 1997 Nov, 53(Pt 6), 777 - 9
A new crystal form of penicillin acylase from Escherichia coli; McVey CE; A new crystal form of penicillin acylase (penicillin amidohydrolase, E.C . 3.5.1.11) from Escherichia coli W (ATCC 11105) is reported . The crystals were grown using a combination of hanging-drop and streak-seeding methods . The crystals are in the monoclinic space group P2(1) with cell dimensions a = 51.52, b = 131.95, c = 64.43 A, beta = 106.12 degrees . There is one heterodimer in the asymmetric unit (V(m) = 2.45 A(3) Da(-1)) and the solvent content is 49% . Preliminary data have been collected to d(min) = 2.7 A using a MAR Research image plate and a rotating-anode X-ray source . Subsequent experiments show diffraction beyond 1.3 A at a synchrotron radiation source.

Biotechnol Prog, 2004 Jul-Aug, 20(4), 1025 - 31
An innovative application of the "flexible" GRID/PCA computational method: study of differences in selectivity between PGAs from Escherichia coli and a Providentia rettgeri mutant; Braiuca P et al.; The original GRID/PCA technique was adapted for the development of a tool potentially useful for the plan of a research strategy in rational enzyme design . The use of the MOVE directive of GRID made it possible to partially take into account protein flexibility, and the multivariate analysis was used as an instrument for focusing only on relevant information related to the differences in enzyme substrate selectivities . The comparison of two different penicillin G acylases, from Escherichia coli and from Providentia rettgeri, was used as a case study; these enzymes are very similar and their reported selectivities differ only for a couple of mutations around the active site . The "flexible" GRID/PCA method was able to correctly predict the observed selectivity differences caused not only by mutations of residues of the active site but also by long range effects on substrate selectivity due to sequence mutations on residues not directly involved in substrate recognition.

J Chromatogr A, 2004 Jul 9, 1042(1-2), 107 - 11
Application of ion-exchange cartridge clean-up in food analysis . VI . Determination of six penicillins in bovine tissues by liquid chromatography-electrospray ionization tandem mass spectrometry; Ito Y et al.; A multiresidue analytical method was developed for the quantification of benzylpenicillin (PCG), phenoxymethylpenicillin (PCV), oxacillin (MPIPC), cloxacillin (MCIPC), nafcillin (NFPC) and dicloxacillin (MDIPC) in bovine tissues using liquid chromatography- electrospray ionization tandem mass spectrometry (LC-ESI MS/MS) with a multiple reaction monitoring technique . Using the deuterated PCG and NFPC as internal standard was effective for improvement of repeatability and accuracy . We chose {M-H-141}- as a monitor ion of MRM analysis and {M-H}- as a precursor ion for each penicillin . Combination of an ion-exchange cartridge clean-up and ion-pair LC enable us to determine the residual penicillins using the standard curves made from standard solutions without the influence of sample matrix on the MS . The average recoveries of PCG, PCV, MPIPC, MCIPC, NFPC and MDIPC from bovine liver, kidney and muscle at the same concentrations as the tolerance levels of PCG (50 microg/kg) ranged from 77 to 101% with the coefficients of variation ranging from 0.7 to 4.2% (n = 5) . The limits of quantification for the six penicillins were 2-10 microg/kg in bovine muscle, liver and kidney (S/N ratio >10).

Appl Environ Microbiol, 2004 Aug, 70(8), 4775 - 83
Uptake of the beta-lactam precursor alpha-aminoadipic acid in Penicillium chrysogenum is mediated by the acidic and the general amino acid permease; Trip H et al.; External addition of the beta-lactam precursor alpha-aminoadipic acid to the filamentous fungus Penicillium chrysogenum leads to an increased intracellular alpha-aminoadipic acid concentration and an increase in penicillin production . The exact route for alpha-aminoadipic acid uptake is not known, although the general amino acid and acidic amino acid permeases have been implicated in this process . Their corresponding genes, PcGAP1 and PcDIP5, of P . chrysogenum were cloned and functionally expressed in a mutant of Saccharomyces cerevisiae (M4276) in which the acidic amino acid and general amino acid permease genes (DIP5 and GAP1, respectively) are disrupted . Transport assays show that both PcGap1 and PcDip5 mediated the uptake of alpha-aminoadipic acid, although PcGap1 showed a higher affinity for alpha-aminoadipic acid than PcDip5 (K(m) values, 230 and 800 microM, respectively) . Leucine strongly inhibits alpha-aminoadipic acid transport via PcGap1 but not via PcDip5 . This difference was exploited to estimate the relative contribution of each transport system to the alpha-aminoadipic acid flux in beta-lactam-producing P . chrysogenum . The transport measurements demonstrate that both PcGap1 and PcDip5 contribute to the alpha-aminoadipic acid flux.

J Biol Chem, 2004 Oct 15, 279(42), 43982 - 9 Epub 2004 Jul 29.
Peptidoglycan amidase MepA is a LAS metallopeptidase; Marcyjaniak M et al.; LAS enzymes are a group of metallopeptidases that share an active site architecture and a core folding motif and have been named according to the group members lysostaphin, D-Ala-D-Ala carboxypeptidase and sonic hedgehog . Escherichia coli MepA is a periplasmic, penicillin-insensitive murein endopeptidase that cleaves the D-alanyl-meso-2,6-diamino-pimelyl amide bond in E . coli peptidoglycan . The enzyme lacks sequence similarity with other peptidases, and is currently classified as a peptidase of unknown fold and catalytic class in all major data bases . Here, we build on our observation that two motifs, characteristic of the newly described LAS group of metallopeptidases, are conserved in MepA-type sequences . We demonstrate that recombinant E . coli MepA is sensitive to metal chelators and that mutations in the predicted Zn2+ ligands His-113, Asp-120, and His-211 inactivate the enzyme . Moreover, we present the crystal structure of MepA . The active site of the enzyme is most similar to the active sites of lysostaphin and D-Ala-D-Ala carboxypeptidase, and the fold is most closely related to the N-domain of sonic hedgehog . We conclude that MepA-type peptidases are LAS enzymes.

J Dairy Sci, 2004 May, 87(5), 1558 - 64
On-farm management decisions to improve beef quality of market dairy cows; Rogers CA et al.; A 3-phase study was conducted to assess on-farm management decisions to reduce antibiotic residue violations and improve carcass characteristics in market (cull) dairy cows . In Phase 1, questionnaires were mailed to dairy producers (n = 142) to determine current on-farm management strategies for reducing antibiotic residues in market dairy cattle . In Phase 2, Holstein market cows (n = 77) were assigned randomly to each of the 3 feeding treatments (0, 30, or 60 d) . Average daily gain (ADG), body condition score (BCS), and carcass characteristics were assessed . Phase 3 determined the meat withdrawal time of Holstein cows (n = 62) administered procaine penicillin G . Eighty-six percent of dairy farms responding to the questionnaire had at least one cow condemned annually, and no producer had a designated feeding protocol for market cows prior to selling . In Phase 2, ADG was greater in cows fed for 30 d (1.4+/-0.6 kg/d) than in cows fed for 60 d (0.9+/-0.4 kg/d) . Additional feeding did not influence the carcass characteristics studied with the exception of kidney, pelvic and heart fat, which was higher in cows fed for 60 d compared with those fed for 0 and 30 d . In Phase 3, 31% of cows treated with procaine penicillin G exceeded the 10-d label withdrawal recommendation by an average of 3.1+/-1.9 d . Feeding market cows may not influence carcass characteristics, but can increase ADG and may ensure that recommended meat withdrawal times for antibiotics are exceeded.

J Infect Chemother, 2004 Jun, 10(3), 172 - 7
Thoracic actinomycosis with mainly pleural involvement; Kobashi Y et al.; A 61-year-old man, who had been diagnosed with pleuritis 5 months earlier, was admitted to our hospital to determine if a tumor shadow that appeared in his right lower lung field on March 2002 was a localized pleural mesothelioma . Although a CT-guided lung biopsy was performed, no definite diagnosis was made . However, because the tumor shadow continued to increase in size, we could not rule out the possibility of a malignant thoracic tumor, and performed video-assisted thoracoscopic surgery (VATS) . Histological examination of the surgically resected tissue led to a diagnosis of thoracic actinomycosis in the main component of the pleura . Because the recurrence of pulmonary actinomycosis was also suspected after surgical treatment, penicillin G was administered intravenously and afterward amoxicillin was administered intraorally . Subsequently, the patient's clinical status improved . We considered a case of thoracic actinomycosis that was suspected to have spread directly from the lung to the chest wall with complicating pleural effusion and remained with organization because there was a pulmonary infiltration shadow in the right upper lobe on chest CT at the first admission.

Childs Nerv Syst, 2004 Oct, 20(10), 726 - 33
Influence of penicillin-induced epileptic activity during pregnancy on postnatal hippocampal nestin expression in rats: light and electron microscopic observations; Baka M et al.; OBJECTS: Current data concerning the effects of maternal epileptic phenomena on newborns are limited . In clinical practice, therefore, it is difficult to suggest proper guidelines on this issue . This study was carried out to investigate the morphological changes in the hippocampus of newborn pups of rats subjected to experimental epilepsy during pregnancy . METHODS: Eighteen Swiss Albino rats were randomly divided into three groups (n=6): experimental group, saline-injected sham surgery group, and intact control group . In the experimental group of rats, an acute grand mal epileptic seizure was induced by 400 IU penicillin-G administration into their intra-hippocampal CA3 region with a stereotaxic device during the 13th day of their pregnancy . On the first neonatal day, pups were perfused with intracardiac fixative solution under anesthesia, and newborn hippocampi were dissected surgically for light and electron microscopic examinations . In an immunohistochemical study using Rat-401 mono-clonal antibody and peroxidase, nestin expression was analyzed in the developing hippocampal tissue . RESULTS: Histologically, normal migration and hippocampal maturation were determined in the newborn rat hippocampus in the control and the sham-operated groups . It was observed that the morphological structure of hippocampus in the experimental group corresponded to the early embryonal period . Most importantly, it was found that nestin (+)cell density was increased in the experimental epilepsy group in contrast to the control and sham groups . CONCLUSION: It has been concluded that epileptic seizures during embryonic life may cause impaired hippocampal neurogenesis and maturation,explaining the potentially harmful effects of epileptic seizures on the embryo at the early stage of neuronal differentiation . This is the first report regarding the alterations in nestin expression in newborn rat hippocampus . In the light of such findings, it will also be necessary to evaluate the functional consequences of a va-riety of epileptic seizures on learning and memory in neonates.

Eur J Pharmacol, 2004 Aug 2, 496(1-3), 23 - 32
Penicillin blocks human alpha1beta1 and alpha1beta1gamma2S GABAA channels that open spontaneously; Lindquist CE et al.; We used the open-channel blocker, penicillin (10 mM), as a tool to investigate if the human alpha1beta1 or alpha1beta1gamma2S gamma-aminobutyric acid type A (GABAA) receptor channels opened in the absence of GABA . Application of penicillin to cells expressing the receptors resulted in a transient inward whole-cell current, the off-current, upon penicillin removal . The amplitude of the off-current was dependent on the duration of the penicillin application, it reversed in polarity at depolarized potentials and exhibited "run-down" similar to the GABA-activated currents . Bicuculline (100 microM) blocked the off-current response . Pentobarbital (50 microM) enhanced the peak off-current amplitude by 2.8 and 3.4 in alpha1beta1 and alpha1beta1gamma2S receptors, respectively . Diazepam (1 microM) only enhanced the off-current peak response in alpha1beta1gamma2S receptors (1.6) and induced the development of an inward current when applied alone . The results are consistent with that the alpha1beta1 or alpha1beta1gamma2) GABAA receptors can open in the absence of GABA and raise the question of what role spontaneous channel openings have in the function of GABAA receptors.

Rinsho Shinkeigaku, 2004 Apr-May, 44(4-5), 296 - 8
{Neurosyphilis presenting the left total ophthalmoplegia: a case report}; Takakura Y et al.; We report a 73-year-old woman with meningitis-type neurosyphilis presenting the main symptom of the left total ophthalmoplegia . Three months after the appearance of the deviation of the eyeball to the inside and ptosis of the left eyelid, the left eyelid was completely closed . On admission, about four months after the appearance of neurosyphilis, she showed paralysis of the left oculomotor nerve, trochlearis nerve and abducens nerve, and the right mydriasis and absent light reflex . She was diagnosed as meningovascular neurosyphilis because syphilitic antibodies reactions in both serum and cerebrospinal fluid were highly positive . We treated her with intravenous infusion drop of penicillin G (eighteen-million units/day) for ten days, and those symptoms mentioned above other than light reflex were completely recovered . Bilateral internal carotid arteries situated close each other at the supraclinoid portion . The internal carotid arteries were not enhanced on Gd-MRI and the stenosis of the arteries were not detected on MRA . However, we suppose that the inflammation of meninges at that portion spreads to the bilateral internal carotid arteries, and that the III, IV and VI nerves close to the left internal carotid artery were damaged . There have been no reports of meningovascular neurosyphilis with the manifestation of unilateral ophthalmoplegia . In the patients of meningovascular neurosyphilis, however, various cranial nerve palsies can be appeared . Therefore we suggest that neurosyphilis should always be taken into consideration as differential diagnosis of cranial nerve palsies.

Curr Treat Options Neurol, 2004 Sep, 6(5), 357 - 375
Stroke in Children with Sickle Cell Disease; Kirkham FJ et al.; Children with sickle disease are at high risk for ischemic stroke and transient ischemic attacks, usually secondary to intracranial arteriopathy involving the terminal internal carotid and proximal middle cerebral and anterior cerebral arteries, which may be diagnosed using transcranial Doppler ultrasound or magnetic resonance angiography (MRA) . Other central nervous system (CNS) complications include seizures and coma, which may be secondary to ischemic stroke, sinovenous thrombosis, reversible posterior leukoencephalopathy, or acute demyelination . The immediate priority after an acute CNS event is to improve cerebral oxygenation with oxygen supplementation to maintain peripheral saturation measured using pulse oximetry between 96% and 99%, and a simple transfusion of packed cells within an hour of presentation if the patient's hemoglobin is less than 10 g/dL . The patient then should have erythrocytapheresis or manual exchange to reduce the hemoglobin S percentage to below 30% . Computed tomography to exclude hemorrhage is mandatory and MR T2-weighted imaging with MRA, fat-saturated imaging of the neck (dissection), MR venography (sinovenous thrombosis), and diffusion-weighted imaging usually distinguishes between arterial ischemic stroke and the differential diagnoses . Comatose patients with widespread focal or global cerebral edema may have good functional outcome after surgical decompression . Anticoagulation may be indicated for dissection or sinovenous thrombosis and steroids for demyelination . Blood pressure should be reduced slowly if raised in patients with reversible posterior leukoencephalopathy . Seizures should be treated aggressively and electroencephalogram monitoring should be done to exclude subclinical seizures if the patient is unconscious . Hemorrhagic stroke may require craniectomy and drainage and/or management of vasospasm . Interventional neuroradiology with coils is an alternative to surgical clipping for aneurysms . For secondary prevention, regular blood transfusion to hemoglobin S of less than 30% reduces the risk of recurrent stroke from approximately 67% to approximately 10% . Hydroxyurea and phlebotomy may be used in patients who are alloimmunized . Moyamoya syndrome is a risk factor for recurrence despite prophylactic blood transfusion . Revascularization may prevent additional stroke . Bone marrow transplantation may be offered to patients with human leukocyte antigen-compatible siblings . Blood transfusion prevents stroke in patients with velocities greater than 200 cm per second on TCD; a phase III trial studying the prevention of the progression of silent infarction is being done . Emerging primary prophylaxis regimens being tested include citrulline and arginine, aspirin, and overnight oxygen supplementation . Physicians caring for children with sickle cell disease also should ensure adequate nutrition, including five servings of fruit and vegetables a day . The role of vitamin supplementation is controversial, particularly when patients must take daily penicillin prophylaxis.

Chirurgia (Bucur), 2004 Mar-Apr, 99(2), 157 - 61
{Hepatic actinomycosis--pseudotumoral form}; Campeanu I et al.; Hepatic actinomycosis is a pretty rare anatomo-clinical entity that often induces a wrong pre-operative diagnosis . By presenting a case of hepatic actinomycosis, apparently primitive and diagnosed pre-operatively as a neoplastic lesion, the authors discuss the diagnosis and treatment of this disease, mentioning that in the solid, tumoral forms, the hepatic resection is necessary . The authors consider that the post-operative addition of antibiotherapy (mega doses of penicillin) is useful for the eradication of inflammatory residual hepatic parenchyma as well as for the cicatrisation of the parietal fistulae.

Minerva Med, 2004 Apr, 95(2), 153 - 8
Plasmodium falciparum parasitized red blood cells modulate the production of endothelin-1 by human endothelial cells; Basilico N et al.; AIM: Plasmodium falciparum (P . falciparum) malaria is the most important parasitic infection of humans, responsible for about 2,000,000 deaths every year . Cytoadherence of P . falciparum parasitized erythrocytes (pRBC) to vascular endothelium contributes to the pathogenesis of severe malaria causing microcirculatory obstruction and subsequent tissue hypoxia . Several cytokines and vasoactive mediators are involved in this process . The aim of this paper was to investigate the production of endothelin-1 (ET-1), a potent vasoconstrictor agent, by endothelial cells from large vessels (human umbilical vein endothelial cells, HUVEC) or the microvasculature (human microvascular endothelial cells, HMEC-1), co-cultured with different strains of P . falciparum pRBC under normoxic or hypoxic conditions . METHODS: HMEC-1, immortalized by SV 40 large Tontigen, were maintained in MCDB 131 medium supplement ed with 10% fetal calf serum, 10 ng/ml of epidermal growth factor, 1 microg/ml of hydrocortisone, 2 mM glutamine, 100 U/ml of penicillin, 100 microg/ml of streptomycin and 20 mM Hepes buffer . The levels of ET-1 in the supernatants were measured by immunoenzymatic assay . RESULTS: The results indicated that IL1-beta and hypoxia were able to induce ET-1 production by both HUVEC and HMEC-1 . However, the co-incubation of HUVEC or HMEC-1 with pRBC induced a dose-dependent decrease of both constitutive and IL1- or hypoxia-induced ET-1 production . The inhibition was independent from the parasite strain used and from the origin of endothelial cells . CONCLUSION: These results show that pRBC by modulating both constitutive and stimulated ET-1 release from endothelial cells can induce modifications of the vascular tone in different anatomical districts . This could be of relevance in the pathogenesis of severe malaria.

J Hist Med Allied Sci, 2004 Jul, 59(3), 441 - 62
Streptomycin, Schatz v . Waksman, and the balance of credit for discovery; Kingston W; A recent article in Nature, arguing that "the misallocation of credit is endemic in science," used Selman Waksman as an illustration, claiming that the true discoverer of streptomycin was one of his graduate students . The article received wide publicity and seriously damaged Waksman's great reputation . What actually happened was that the success of penicillin stimulated Merck to fund research by Waksman, a soil scientist, into the collection of actinomycetes that he had assembled over thirty years . He applied the systematic, uncreative testing techniques that had made the German pharmaceutical industry so successful to these, and streptomycin was discovered within a matter of months . Work in the Mayo Institute then showed that it was marvelously effective against tuberculosis, and Waksman received the Nobel Prize for it in 1952 . The test that turned out to be the crucial one could have been carried out by any of several students, but the lucky one was Albert Schatz . He then sued the university for a share of the royalties payable by Merck and also petitioned the Nobel committee to include him in the award . Although he obtained a very substantial out-of-court settlement, this probably damaged his subsequent academic career, and he has never ceased to argue his case for recognition, of which the Nature article is a reflection . To claim that Waksman took credit properly due to Schatz is to fail to understand that once pharmaceutical research had become primarily a matter of large-scale, routine testing, little individual creativity was left in this work . Credit for any successful results must therefore be given to whoever is the originator or director of a particular program . Nature refused to publish evidence that this case could not be used as an example of misallocation of credit for discovery . This in itself illustrates that editors of scientific journals should be every bit as mindful of scientists' reputations as they are of scientific facts.

Am J Health Syst Pharm, 2004 Jun 15, 61(12), 1271 - 5
Pharmacist-managed service providing penicillin allergy skin tests; Wall GC et al.; PURPOSE: A penicillin allergy skin-testing service run by pharmacists is described . SUMMARY: A board-certified allergist trained pharmacists at a tertiary care teaching hospital to administer penicillin allergy skin tests and interpret the results . A major objective of the service was to avoid unnecessary use of vancomycin and quinolones in patients claiming but not actually having a penicillin allergy . Patients with a severe type I reaction to penicillin during the preceding five years, patients with a confirmed history of a type II-IV reaction to penicillin, and severely immunosuppressed patients were not eligible for testing . As of July 2003, 26 patients had been enrolled in the service . A type I penicillin reaction was ruled out by the drug allergy history for 3 patients . The results were negative in 22 of the 23 patients who received skin testing, and in 1 the result was indeterminate . A penicillin or a beta-lactam antibiotic was administered to all 26 patients . No patient had a significant adverse reaction to skin testing or drug administration . CONCLUSION: A pharmacist-managed penicillin allergy skin-testing service was well received by physicians and showed potential to avoid unnecessary use of alternative antibiotics.

Perspect Biol Med, 2004 Spring, 47(2), 189 - 98
Hitler's penicillin; Wainwright M; During the Second World War, the Germans and their Axis partners could only produce relatively small amounts of penicillin, certainly never enough to meet their military needs; as a result, they had to rely upon the far less effective sulfonamides . One physician who put penicillin to effective use was Hitler's doctor, Theodore Morell . Morell treated the Fuhrer with penicillin on a number of occasions, most notably following the failed assassination attempt in July 1944 . Some of this penicillin appears to have been captured from, or inadvertently supplied by, the Allies, raising the intriguing possibility that Allied penicillin saved Hitler's life.

Cell Tissue Bank, 2001, 2(4), 217 - 24
Improved islet survival and in vitro function using solubilized small intestinal submucosa; Lakey JR et al.; In vitro proliferation of isolated pancreatic islets has become an area of great interest given the scarcity of clinical islet donors and the islet mass requirements for clinical islet transplantation . Small intestinal submucosa (SIS), a naturally occurring extracellular matrix, has been investigated to promote wound healing, tissue remodeling and cell growth . This study evaluated recovery and function of isolated canine pancreatic islets following in vitro tissue culture . Pancreatic islets were isolated from mongrel dogs using standard surgical procurement followed by intraductal collagenase distension, mechanical dissociation and EuroFicoll purification . Groups of purified islets were cultured in a humidified atmosphere of 95% air and 5% CO(2) for 48 hours in standard islet culture conditions of CMRL 1066 tissue culture media (Gibco) which had been supplemented with 25microM HEPES, penicillin/streptomycin and either 10% heat inactivated fetal calf serum (FCS, Gibco) or solubilized SIS solution (Cook Biotech, Inc., West Lafayette, IN) . The mean recovery of islets following the culture period was determined by sizing duplicate counts of a known volume and viability was assessed by static incubation with low glucose (2.8 mM), high glucose (20 mM) and high glucose solution supplemented with 50 microm IBMX solution . Remaining islets were embedded histologically . From a consecutive series of six culture experiments, a significantly higher (p < 0.05) recovery of islets co-cultured with SIS was observed when compared to controls . Mean islet recovery was 84.5 +/- 2.9% (mean +/- SEM) from the SIS cultured group compared with 64.7 +/- 4.5% from the control group cultured in FCS (p < 0.05, n=6) . Islets from the SIS treated group exhibited a significantly higher (p <, 0.05) insulin response to the high glucose stimulus than islets cultured in the standard FCS cultured solution . The calculated stimulation index was 12.3 +/- 3.4 for the SIS-treated group compared with 5.6 +/- 1.8 for the standard cultured group (p < 0.05) . The overall mean numbers of islets recovered following in vitro culture was also higher in the SIS-treated group . The proportion of islets with a mean diameter >150 microm increased from 24% to 31% in the SIS-treated group, whereas the same proportion decreased to 18% from 22% in the control (FCS-treated) group . Histological evaluation of fixed tissue samples collected following the culture period identified insulin and glucagon-secreting cells in the SIS and FCS treated groups, however a higher frequency of insulin positive cells were detected consistently in the SIS treated group . A proliferation marker (PCNA) identified positive cells within both groups as well . This study suggests that co-culture of freshly isolated canine islets in medium supplemented with solubilized SIS can improve the post-culture recovery and in vitro islet function . Future investigations will focus on the cellular interactions of SIS, both in vitro and in vivo.

Protein Eng Des Sel, 2004 May, 17(5), 473 - 80 Epub 2004 Jul 14.
Structural and kinetic studies on ligand binding in wild-type and active-site mutants of penicillin acylase; Alkema WB et al.; Penicillin acylase catalyses the condensation of Calpha-substituted phenylacetic acids with beta-lactam nucleophiles, producing semi-synthetic beta-lactam antibiotics . For efficient synthesis a low affinity for phenylacetic acid and a high affinity for Calpha-substituted phenylacetic acid derivatives is desirable . We made three active site mutants, alphaF146Y, betaF24A and alphaF146Y/betaF24A, which all had a 2- to 10-fold higher affinity for Calpha-substituted compounds than wild-type enzyme . In addition, betaF24A had a 20-fold reduced affinity for phenylacetic acid . The molecular basis of the improved properties was investigated by X-ray crystallography . These studies showed that the higher affinity of alphaF146Y for (R)-alpha-methylphenylacetic acid can be explained by van der Waals interactions between alphaY146:OH and the Calpha-substituent . The betaF24A mutation causes an opening of the phenylacetic acid binding site . Only (R)-alpha-methylphenylacetic acid, but not phenylacetic acid, induces a conformation with the ligand tightly bound, explaining the weak binding of phenylacetic acid . A comparison of the betaF24A structure with other open conformations of penicillin acylase showed that betaF24 has a fixed position, whereas alphaF146 acts as a flexible lid on the binding site and reorients its position to achieve optimal substrate binding.

Equine Vet J, 2004 Jul, 36(5), 370 - 5
Prevention of ischaemia-induced small intestinal adhesions in foals; Sullins KE et al.; REASONS FOR PERFORMING STUDY: Treatments addressing variously theorised pathophysiological mechanisms of small intestinal adhesions have been reported . This study applied those classes of treatments to the most clinically relevant aetiology of post operative adhesions . HYPOTHESIS: Treatments addressing the pathophysiology of ischaemia-reperfusion induced adhesions would accordingly reduce the incidence of adhesions from this model . METHODS: Four classes of treatments were administered for 72 h to 16 foals subjected to complete ischaemia followed by reperfusion to create peritoneal adhesions . These groups were: 1) FPG group--flunixin meglumine (1.1 mg/kg bwt i.v., divided q.i.d.), potassium penicillin G (22,000 iu/kg bwt i.v., q.i.d.) and gentamicin (2.2 mg/kg bwt i.v., t.i.d.); 2) HEP group--heparin (80 iu/kg bwt subcut., b.i.d.); 3) DMSO group--dimethylsulphoxide (DMSO) (20 mg/kg bwt {diluted in 500 ml normal saline} i.v., b.i.d.); and 4) SCMC group--sodium carboxymethylcellulose (500 ml 3% sterile solution intraperitoneally, administered only at the beginning of surgery) . RESULTS: Post operative intestinal obstruction did not occur in any foal . After 10 days, necropsy revealed bowel-to-bowel adhesions in none of the FPG or DMSO groups, in 2/4 of the SCMC group, in 3/4 of the HEP group and 5/6 foals subjected to the procedure without treatment (UIR group) . CONCLUSIONS: Inhibition of the inflammation associated with ischaemia and reperfusion in foals treated with FPG or DMSO decreased small intestinal adhesions in foals . POTENTIAL RELEVANCE: Although anti-inflammatory therapy was shown to eliminate bowel-bowel adhesions in this controlled study, it must be remembered that clinical cases are without control . These therapies are advised to improve the result but are unlikely to eliminate the problem.

J Card Surg, 2004 Jul-Aug, 19(4), 356 - 7
Ruptured giant syphilitic aneurysm of the descending aorta in an octogenarian; Bossert T et al.; Syphilis can lead to saccular aneurysms of the thoracic aorta . Today syphilitic aortic aneurysms are rare . The average time from primary infections to the development of aortic aneurysms is 10 to 15 years . An 83-year-old man was admitted with a giant aneurysm of the descending thoracic aorta . The patient had first experienced subacute pain in the left hemithorax some weeks previously . Computer tomography scan detected an 11 x 11 cm aneurysm of the descending aorta . Serodiagnostic tests for syphilis were highly positive . Femoro-femoral bypass was initiated and a tube graft was interposed . The postoperative course was uneventful, the patient was discharged at the twentieth postoperative day . Histological examination of the aneurysmal wall showed typical syphilitic changes . Postoperatively, Penicillin G was given for 6 months . Three years later the patient remains asymptomatic . Although extremely rare today, tertiary syphilis should be considered in the differential diagnosis of thoracic aneurysms . In selected octogenarians replacement of the descending aorta is possible.

Rev Saude Publica, 2004 Jun, 38(3), 429 - 37 Epub 2004 Jul 08.
{Pharmacists' knowledge of sanitary legislation and professional regulations}; Silva LR et al.; OBJECTIVE: To characterize the profile of pharmacists employed as technical supervisors in drugstores and evaluate their knowledge regarding certain aspects of the legislation controlling drugstores and the profession in general . METHODS: Based on 175 drugstores in the city of Ribeirao Preto, southeastern Brazil, 100 pharmacists/technical supervisors were randomly selected . Data collection was done by means of in-person interviews, and was guided by a questionnaire evaluating knowledge and attitudes . Data were processed and analyzed using Epi Info and Stata software . Associations were sought between dependent and independent variables using Pearson's chi-squared and Fisher's exact tests . RESULTS: Most pharmacists were women (64%), aged 22-29 years (47%), graduated approximately three years prior to data collection, trained to work in the pharmaceutical industry (36%) or in clinical analysis (29%) . Pharmacist's knowledge of sanitary legislation was considered as insufficient for 28% of subjects, regular for 50%, and good for 22% . Low levels of knowledge were observed regarding the legal requirement for the presence of a pharmacist during the entire drugstore opening hours, pharmacists' attributions, sale of antibiotics, and penicillin administration . It was found that most professionals have difficulties handling the concepts of 'generic' and 'similar' drugs . Low level of knowledge was not associated with any of the independent variables, indicating that this is a generalized phenomenon, i.e., one present among pharmacists of all age groups and both sexes, irrespective of the time since graduation, institution attended, and modality of graduation, among others . CONCLUSIONS: We conclude that training in the field of drug pharmaceutical care, during undergraduate studies and, especially, during traineeship in pharmacies and drugstores is deficient . It is necessary to divulge information concerning sanitary legislation so that pharmacists may fully exert their profession, without risk of legal threats or hazard to the population.

Immunol Allergy Clin North Am, 2004 Aug, 24(3), 445 - 61, vi
Dilemmas and controversies in penicillin allergy; Thethi AK et al.; Since the initial reports of penicillin and beta-lactam drugs causing allergic reactions, much has been elucidated regarding their pathophysiology and mechanism of action . Despite advances in testing for penicillin allergy, with IgE antibodies and skin tests available for the major and minor determinants of penicillin, these reactions remain a challenge to all physicians . They have characteristically been classified according to mechanism and time . Herein, the authors propose a classification system of penicillin allergy based on immunologic mechanisms.

Immunol Allergy Clin North Am, 2004 Aug, 24(3), 425 - 43, vi
Drug desensitization; Solensky R; Although most patients who report a history of drug allergy are not truly allergic, this article focuses on those individuals with confirmed drug hypersensitivity . Desensitization is an immunologic method that allows allergic patients to receive the sensitizing drug safely . Classically, the procedure is applied in IgE-mediated reactions, but its use has been extended to other drug reactions . The most common clinical scenarios wherein desensitization may be needed are reviewed . The discussion includes rapid desensitization of patients with IgE-mediated allergies to penicillin and other classes of antibiotics, and sulfonamide desensitization of HIV-positive patients.

J Allergy Clin Immunol, 2004 Jul, 114(1), 118 - 24
Advances in allergic skin disease, anaphylaxis, and hypersensitivity reactions to foods, drugs, and insect stings; Sicherer SH et al.; This review highlights some of the research advances in allergic skin disease, anaphylaxis, and hypersensitivity reactions to foods, drugs, and insect venom that were reported primarily in the Journal of Allergy and Clinical Immunology from 2002 through 2003 . Among the topics highlighted are new insights into the pathogenesis of atopic dermatitis and potential strategies for more effective treatment of the atopic march . Patients should remain supine with raised legs during anaphylactic shock because upper body elevation could result in sudden death from loss of venous return to the heart . A major advance in food allergy was that humanized, monoclonal anti-IgE antibody showed protection against peanut-induced anaphylaxis . In addition to studies elucidating mechanisms of drug hypersensitivity, a clinical study showed patients with a history of prior penicillin allergy with negative penicillin allergy test results are unlikely to experience reactions or resensitization on subsequent oral courses of penicillin . Lastly, there are new recommendations for patients with convincing insect sting reaction histories but negative skin test responses to venom .

Biotechnol Appl Biochem . 2004 Jul 8; {Epub ahead of print}
Optimization of penicillin G acylase multipoint immobilization onto glutaraldehyde-chitosan beads; Adriano WS et al.; The objective of this work was to study the immobilization of penicillin G acylase (PGA) from E . coli onto chitosan-glutaraldehyde beads by multipoint covalent binding . This process was optimized using a 2 3 experimental design . The selected parameters for this study were: glutaraldehyde concentration, phenyl acetic acid concentration and sodium borohydride concentration . Three responses were chosen: immobilization yield, stabilization factors of enzyme derivatives at high temperature and alkaline pH . All the runs at the maximum (+1) and minimum (-1) levels were carried out at random . Three experiments were carried out at the center point coded as zero, for experimental error estimation . Concerning immobilization yield, the main effects were glutaraldehyde concentration and phenyl acetic acid concentration . In the case of stabilization factor at 50 degrees C and alkaline pH, the main effects were glutaraldehyde concentration, sodium borohydride concentration and the interaction between them.

Curr Opin Allergy Clin Immunol, 2004 Aug, 4(4), 261 - 6
Immediate allergic reactions to betalactams: facts and controversies; Gomez MB et al.; PURPOSE OF REVIEW: To analyse the available data in the field of immediate allergic reactions to beta-lactams, with particular emphasis on more recent studies, and to comment on the future role of this group of antibiotics . RECENT FINDINGS: The world of beta-lactams has become more complex than initially thought, due to the increased number of chemical structures available, the wide variety of indications for their use in treating different infectious diseases, and possibly also due to the interaction of other as yet undetermined factors . Benzyl penicillin, the original inducer of allergic reactions, has now largely been replaced by amoxicillin and, to a lesser extent, by cephalosporins in inducing IgE-mediated allergic reactions . These structures often share extensive cross-reactivity, eliciting clinical reactions to many compounds, especially amongst penicillins . In other circumstances selective responses are observed which are restricted to one group or one single compound, as occurs in the group of cephalosporins . The application of new determinants for skin testing and the use of adapted in-vitro studies have enabled these findings to be confirmed in detail . SUMMARY: Results indicate that evaluation of immediate reactions to beta-lactams requires the use of several determinants for both in-vitro and in-vivo testing, and which must reflect the relevant drug involved in eliciting the response . This tendency will be strengthened in the future if use of benzyl penicillin continues to decrease as a drug to which populations are exposed.

Ann Allergy Asthma Immunol, 2004 Jun, 92(6), 619 - 28
Anaphylaxis during surgical and interventional procedures; Thong BY et al.; OBJECTIVE: To describe the current evidence-based knowledge of the causes, diagnostic evaluation, and treatment of patients with anaphylaxis associated with surgical and interventional procedures . DATA SOURCES: Articles published between 1966 and 2003 were identified in MEDLINE using the keywords anaphylactoid, anaphylaxis, anesthetics, antibiotics, cephalosporins, contrast media, colloids, flow cytometry, hypersensitivity, latex, neuromuscular depolarizing agents, neuromuscular nondepolarizing agents, penicillins, radioallergosorbent test, skin test, and vancomycin . Additional studies were identified from article reference lists . STUDY SELECTION: Relevant, peer-reviewed original research articles and reviews . RESULTS: Neuromuscular blocking agents, natural rubber latex, antibiotics, and induction agents are the most common causes of anaphylaxis during surgical and interventional procedures . Colloids, opioids, and radiocontrast media probably account for less than 10% of all reactions . Newer agents implicated in anaphylaxis include isosulphan blue and chlorhexidine . Skin tests are useful for evaluating allergic reactions to anesthetic agents and penicillins and for selecting alternative agents . Skin testing and specific IgE measurements for latex vary in allergen standardization and sensitivity and specificity, respectively . Flow cytometric allergen stimulation tests show promise in differentiating allergic from idiosyncratic ("pseudoallergic") reactions . Drug desensitization has been shown to be useful for penicillin anaphylaxis . Premedication with histamine receptor antagonists and corticosteroids helps prevent or attenuate radiocontrast media reactions . CONCLUSIONS: Anaphylaxis during surgical and interventional procedures may be difficult to evaluate because of the rapid, successive use of multiple drugs or diagnostic agents . Careful analysis of anesthetic records and diagnostic tests for all the putative agents are necessary to ensure a complete evaluation.

J Chromatogr B Analyt Technol Biomed Life Sci, 2004 Aug 25, 808(1), 111 - 5
Penicillin acylase purification with the aid of hydrophobic charge induction chromatography; Coulon D et al.; The aim of this work was to test a chromatographic support, 4-mercaptoethyl pyridine (4-MEP) Hypercel, for penicillin acylase purification by using pure penicillin acylase and crude extract . Two equilibration buffers with various salt concentrations and different flow rates were tested . The relationships between electrostatic and hydrophobic interactions and proteins are demonstrated . (NH4)2SO4 proved preferable because no salting-in occurred, contrary to NaCl . The recovery and purification fold were similar to those obtained in pseudo-affinity chromatography with a three-fold reduction of the (NH4)2SO4 concentration.

Arch Pediatr, 2004 Jul, 11(7), 843 - 53
{Clinical effectiveness of seven-valent pneumococcal conjugate vaccine (Prevenar) against invasive pneumococcal diseases: prospects for children in France}; Black S et al.; A seven-valent pneumococcal polysaccharide-CRM197 carrier protein conjugate vaccine (PNC7V; Prevenar, Wyeth, Paris) targets the serotypes (belonging to serogroups 14, 6, 19, 18, 23, 9, and 4) most often responsible for invasive pneumococcal disease (IPD) among children . A randomized, controlled, double-masked study among 37,868 children in northern California (Northern California Kaiser Permanente, USA) provided a per protocol vaccine efficacy value of 97.7% against invasive pediatric IPD due to the vaccine serotypes . The PNC7V vaccine was registered by the European Agency for the Evaluation of Medicinal Products (EMEA) in October 2000; a favorable "Community Marketing Decision" under the Centralized Procedure was granted in February 2001 . PNC7V was recommended for most infants by the Conseil Superieur d'Hygiene Publique de France in March 2002, on the advice of the Comite Technique des Vaccinations, as S . pneumoniae in children less than 2 years of age is the primary cause of bacterial meningitis and of mortality associated with community-acquired bacterial infections . The theoretical coverage of the vaccine towards pneumococcal invasive disease in France is about 80%, which represents one of the best serotype coverage estimates in Europe, and vaccines serotypes account for 90% of penicillin-nonsusceptible strains . Distinctive characteristics in France in terms of epidemiology, life style, and therapeutic attitudes justify a precise follow up of the consequences of the vaccination on a national level during the coming years . Hence, surveillance programs have been established: (i) to ascertain the future impact of large-scale PNC7V vaccination on invasive pneumococcal disease incidence, (ii) to follow the evolution of carriage and ecology of the pneumococcus, and (iii) to establish an active "vaccinovigilance".

J Hazard Mater, 2004 Aug 9, 112(1-2), 105 - 13
Pre-treatment of penicillin formulation effluent by advanced oxidation processes; Arslan-Alaton I et al.; A variety of advanced oxidation processes (AOPs; O3/OH-, H2O2/UV, Fe2+/H2O2, Fe3+/H2O2, Fe2+/H2O2/UV and Fe3+/H2O2/UV) have been applied for the oxidative pre-treatment of real penicillin formulation effluent (average COD0 = 1395 mg/L; TOC0 = 920 mg/L; BOD(5,0) approximately 0 mg/L) . For the ozonation process the primary involvement of free radical species such as OH* in the oxidative reaction could be demonstrated via inspection of ozone absorption rates . Alkaline ozonation and the photo-Fenton's reagents both appeared to be the most promising AOPs in terms of COD (49-66%) and TOC (42-52%) abatement rates, whereas the BOD5 of the originally non-biodegradable effluent could only be improved to a value of 100 mg/L with O3/pH = 3} treatment (BOD5/COD, f = 0.08) . Evaluation on COD and TOC removal rates per applied active oxidant (AOx) and oxidant (Ox) on a molar basis revealed that alkaline ozonation and particularly the UV-light assisted Fenton processes enabling good oxidation yields (1-2 mol COD and TOC removal per AOx and Ox) by far outweighed the other studied AOPs . Separate experimental studies conducted with the penicillin active substance amoxicillin trihydrate indicated that the aqueous antibiotic substance can be completely eliminated after 40 min advanced oxidation applying photo-Fenton's reagent (pH = 3; Fe(2+):H2O2 molar ratio = 1:20) and alkaline ozonation (at pH = 11.5), respectively.

Graefes Arch Clin Exp Ophthalmol, 2004 Aug, 242(8), 682 - 6 Epub 2004 Jun 22.
Actinomyces canaliculitis: diagnosis of a masquerading disease; Briscoe D et al.; BACKGROUND: To review the diagnosis and management of seven cases of Actinomyces canaliculitis . METHODS: Culture of discharge was performed in six of seven patients with Actinomyces canaliculitis using a PD Plus/F blood culture bottle . All patients were treated by canaliculotomy with curettage of dacryoliths, followed by treatment with systemic penicillin and Sulphacetamide drops over a period of 3-6 months . Part of the curetted concretions was fixed on a glass slide and part was sent to the laboratory for culture . RESULTS: Four patients were women and three men with age ranging between 43 and 90 years . The average time lapse between onset of symptoms until diagnosis was 3 years . All cases presented with epiphora, chronic conjunctivitis, palpably thickened canaliculus, and yellow punctal discharge . Diagnosis was achieved by culture of discharge in three of six cases, culture of concretions in three of five cases, and staining of dacryoliths in all seven cases . Follow-up ranged between 12 and 48 months . The canaliculitis resolved completely and all patients have patent canalicula . CONCLUSIONS: Actinomyces canaliculitis presents with epiphora, chronic purulent conjunctivitis, a palpably thickened canaliculus, and yellow punctual discharge . In suspect cases canuliculotomy and curettage should be performed, although canalicular reconstruction is generally unnecessary . Culture of discharge and concretions using PD Plus/F blood culture medium gave improved results over accepted norms . Fixation of smeared concretions on a slide in alcohol is simple and is diagnostic of the disease . We recommend long-term systemic penicillin treatment in Actinomyces canaliculitis.

Carbohydr Res, 2004 Jul 12, 339(10), 1673 - 8
The influence of small oligosaccharides on the immune system; Bland EJ et al.; In this study, oligosaccharides known to enhance the synthesis of penicillin by Penicillium chrysogenum have been presented to human immune cells and their effect measured . In addition a range of commercially available oligosaccharides have been tested . Results obtained indicate that oligosaccharides with a degree of polymerisation greater than 6 and with a tendency to form helical structures are most effective at influencing the immune system as measured by the production of reactive oxidising species . Laminariheptaose has been shown to increase reactive oxidising species production by up to 25%, whilst mannan-oligosaccharides with a DP of 6 to 7 decrease production by up to 44% . These and other results show that the immune system can recognise subtle differences in oligosaccharides and that these oligosaccharides could potentially be used to modulate the immune response.

Lancet Infect Dis, 2004 Jul, 4(7), 456 - 66
Syphilis and HIV: a dangerous combination; Lynn WA et al.; HIV and syphilis affect similar patient groups and co-infection is common . All patients presenting with syphilis should be offered HIV testing and all HIV-positive patients should be regularly screened for syphilis . Syphilis agent may enhance the transmission of the other, probably through increased incidence of genital ulcers . Detection and treatment of syphilis can, therefore, help to reduce HIV transmission . Syphilis may present with non-typical features in the HIV-positive patient: there is a higher rate of symptomless primary syphilis and proportionately more HIV-positive patients present with secondary disease . Secondary infection may be more aggressive and there is an increased rate of early neurological and ophthalmic involvement . Diagnosis is generally made with serology but the clinician should be aware of the potential for false-negative serology in both primary and, less commonly, in secondary syphilis . All HIV-positive patients should be treated with a penicillin-based regimen that is adequate for the treatment of neurosyphilis . Relapse of infection is more likely in the HIV-positive patient and careful follow-up is required.

J Vet Med A Physiol Pathol Clin Med, 2004 Apr, 51(3), 155 - 6
Pregnancy rate following post-insemination intrauterine treatment of endometritis in dairy cattle; Shams-Esfandabadi N et al.; Summary Of 1500 examined Holstein cows in milk, there were 315 cows with mucopurulent discharges at the time of insemination (21%) . Twenty-four hours after insemination, the infected animals randomly received no treatment (group I, control, n = 93), intrauterine infusion of 1 g oxytetracycline (group II, n = 63) and intrauterine infusion of 5 million IU procain penicillin G sodium (group III, n = 159) . First service conception rate following treatment was 48.3, 49.2 and 47.7% in groups I, II and III, respectively . In conclusion, treatment with either antibiotic had no advantage relative to the control on first service conception rate.

Chemistry, 2004 Jun 21, 10(12), 2977 - 82
Charge density and experimental electrostatic potentials of two penicillin derivatives; Wagner A et al.; Two penicillin derivatives, the active penamecillin and the inactive penamecillin-1beta-sulfoxide, were used to study the relationship between their charge density and their activity . Single crystals of both compounds were measured at the synchrotron beamline F1 at the HASYLAB/DESY, at 100 K and up to resolutions of around 0.4 A . Experimental charge densities were obtained by using the Hansen-Coppens multipole formalism . The cleavage of the amide bond in the beta-lactam ring is of paramount importance in the mechanism of action of penicillins . Topological analysis of this bond in terms of Bader's AIM theory showed that its strength is equal in both compounds; therefore a direct influence of bond strength on the activity can be ruled out . However, the two derivatives differ significantly in their experimental electrostatic potentials . These differences are discussed and provide further insight into the chemistry and activity of penicillins.

Arch Neurol, 2004 Jun, 61(6), 953 - 6
Acute bilateral inferior cerebellar infarction in a patient with neurosyphilis; Umashankar G et al.; BACKGROUND: Bilateral simultaneous infarction in the territories of the posterior inferior cerebellar arteries (PICAs) is rare but was recently reported with increasing frequency, probably because of the wider availability of magnetic resonance imaging . The cause of these infarcts is believed to be atherosclerotic or embolic occlusion of a dominant PICA, which perfused the territories of the medial branches of both PICAs . RESULTS: We encountered a patient with simultaneous infarction in the territories of the medial branches of both PICAs . The clinical course, imaging results, and laboratory findings are presented . The patient was diagnosed with neurosyphilis based on a history of chancre, positive serum and cerebrospinal serologies, cerebrospinal pleocytosis, and increased intrathecal immunoglobulin synthesis . We believe that meningovascular syphilis caused the bilateral cerebellar infarct via presumed thromboangiitis of a dominant PICA perfusing both cerebellar hemispheres . The patient was treated with intravenous high doses of penicillin . CONCLUSIONS: This case reminds us that meningovascular syphilis should be considered in younger patients with stroke . Patients with bilateral cerebellar infarction may solely have symptoms of vertigo and ataxia but can develop life-threatening complications because of edema of the infarcted tissue with resultant hydrocephalus and pressure on the brainstem.

Pediatr Allergy Immunol, 2004 Jun, 15(3), 278 - 80
Penicillin sensitivity among children without a positive history for penicillin allergy; Cetinkaya F et al.; To establish the prevalence of positive penicillin skin tests among outpatients without any drug reaction history . Skin testing was performed in 147 children (aged 6-13 years) who had had received a penicillin preparation at least three times in the last 12 months without any allergic reaction . Before testing, detailed pediatric and allergy history were learned and then all children were tested with benzyl penicilloyl polylysin (PPL) and mixture of minor antigenic determinants . The test procedures were made epidermally and intradermally subsequently in every subject . The overall frequency of positive skin reactions to penicillin antigens was 10.2% . A mild systemic reaction was observed in one of the children during testing with PPL . We concluded that frequent use of penicillin and other beta-lactam antibiotics leads to sensitization of children in our study population despite these children seem to be asymptomatic during testing time .

Lancet . 2004 Jun 19;363(9426):2087.
Depressing research; Roth D et al.; Suppression of the publication of negative trials of serotonin-selective reuptake inhibitors (SSRI) in children (Apr 24, p 1335) is more than just a matter of "confusion, manipulation, and institutional failure" . It is a crime . To blandly illustrate its severity, we can analogise the situation as follows: would you be concerned if a colleague prescribed penicillin to a child who had an uncomplicated upper respiratory tract infection of viral aetiology? Would you be more concerned if you heard that this child had a serious anaphylactic reaction to the penicillin at home? And how much more concerned would you be if you found out that the prescribing doctor was previously aware of the child's severe penicillin allergy? The latter scenario could be deemed malpractice . How, then, is it acceptable for pharmaceutical companies to suppress publication of SSRI studies that showed a lack of efficacy and an increased risk of serious adverse events in the children and adolescents in experimental trial groups (other than for fluoxetine)? Intentional concealment of these data, an accusation for which there is already public evidence, must be considered a form of corporate violence.

J Eur Acad Dermatol Venereol, 2004 Jul, 18(4), 484 - 6
Congenital syphilis presenting with nephrotic syndrome and leucocytoclastic vasculitis; Cam H et al.; Nephrotic syndrome is a well-recognized entity in congenital syphilis but leucocytoclastic vasculitis has not yet been described . We report a case of nephrotic syndrome and leucocytoclastic vasculitis associated with congenital syphilis in a 45-day-old male infant who did well after treatment with intravenous penicillin.

J Eur Acad Dermatol Venereol, 2004 Jul, 18(4), 429 - 34
Otosyphilis: report on six cases; Klemm E et al.; Syphilis is a multisystemic disease that may also affect the inner ear . The objective of this study was to investigate the frequency, clinical presentation and outcome of otosyphilis . A retrospective analysis of inpatients seen by a team of ENT specialists and dermatologists at a teaching hospital in Dresden, Germany, during 1986-2000 . Six cases of otosyphilis had been diagnosed . None was related to risk factors such as HIV infection or drug abuse . We identified four female and two male patients, age range 25-58 years . Four patients suffered from syphilis stage II, one from syphilis stage and another from congenitial syphilis . ENT complaints included loss or impairment of hearing, tinnitus and nystagmus . All were treated with penicillin G . Adjuvant therapy included systemic corticosteroids oral pentoxifillin in two patients each . Improvement of ENT symptoms was achieved in all but one patient, who suffered from congenitial syphilis . This study confirms that otosyphilis is still a complication of syphilis in developed countries . The first line therapy is systemic penicillin G . There is a lack of controlled trials for adjuvant treatments such as corticosteroids and pentoxifillin . Clinical cooperation between dermatologists/venereologists and ENT specialists supports the best outcome.

J Eur Acad Dermatol Venereol, 2004 Jul, 18(4), 426 - 8
Intramuscular bipenicillin vs . intravenous penicillin in the treatment of erysipelas in adults: randomized controlled study; Zeglaoui F et al.; The objective of the study was to evaluate the efficacy of intramuscular penicillin: mixture of benzyl penicillin and procain penicillin (2 MU x 2 times daily) and intravenous benzyl penicillin (4 MU x 6 times daily) in the treatment of hospitalized adult patients with erysipelas . A prospective randomized unicentric trial was conducted . In total, 112 patients entered the study; 57 in the intramuscular group and 55 patients in the intravenous group completed the trial . The failure rate was 14% for intramuscular group and 20% for the intravenous group (P = 0.40) . Local complications such as of the leg abscesses were observed in the two groups (intravenous 9.1%, intramuscular 7%; P = 0477) . Of the patients treated with intravenous benzyl penicillin, 25.5% presented complications related to the route (venitis) . Intramuscular penicillin should be considered an effective and well-tolerated treatment of erysipelas in adult patients.

Transplant Proc, 2004 May, 36(4), 1175 - 7
Improved in vitro function of islets using small intestinal submucosa; Woods EJ et al.; Transplantation of human pancreatic islets has been demonstrated to be a viable alternative to exogenous insulin therapy for diabetes mellitus . However, optimum results require transplantation of islets from two to three pancreas donors after a minimum number of days in culture . This implies that a substantial part of the transplanted islet mass may be nonfunctional . This study investigates the ability of an optimized technique to retain islet function using porcine-derived small intestinal submucosa (SIS) during in vitro culture . Groups of purified human islets were cultured for 3 weeks in modified standard islet culture conditions of CMRL = 1066 tissue culture medium supplemented with 25 mmol/L HEPES, penicillin/streptomycin, and a commercial insulin-transferin-selenium (ITS) supplement . Islets (50 to 200 IE/condition; n = 5 preparations) were cultured in plates containing noncoated Biopore membrane inserts alone, or on inserts that had been covered with SIS . Function was assessed by static incubation with low (4 mmol/L), or high (20 mmol/L) glucose at the end of each week . Glucose-stimulated release of human insulin was measured by radioimmunoassay (Linco, St . Charles, Missouri) . Remaining islets were stained and evaluated visually . Neither culture condition resulted in significantly different basal secretion until week 3 (P =.05) . However, by the end of week 2 and for the duration of the experiment thereafter, SIS-treated islets exhibited a higher SI (P <.05) . At the end of the experiment, islets cultured on the SIS exhibited excellent morphology, with greater than 90% staining positive with Dithizone . Islets cultured on the inserts alone lost their initial morphology, becoming "loose" in appearance . The results of this study indicate that SIS enables enhanced function of islets in vitro as compared to non-SIS supported culture conditions.

Cell Transplant, 2004, 13(3), 237 - 43
Polyvinyl pyrrolidone: a novel cryoprotectant in islet cell cryopreservation; El-Shewy HM et al.; The present study was performed on the basis of the hypothesis that the low molecular weight (MW) compounds, DMSO and glycerol, permeate the cell and interact hydrophobically with intracellular proteins, thereby perturbing the cytoskeletal architecture of frozen cells and diminishing islet cell integrity and function . Isolated rat islets were cultured overnight (18-24 h) at 37 degrees C in RPMI medium supplemented with 10% fetal calf serum and 1% mixture of penicillin/streptomycin . Using a programmable temperature controller, samples of precounted islets were then frozen under liquid nitrogen, in the presence of either 2 M DMSO (MW = 0.078 kDa), 3 M glycerol (MW = 0.092 kDa), 5% polyethylene glycol (PEG, MW = 20 kDa), or 10% polyvinylpyrrolidone (PVP, MW = 40 kDa), and stored at -80 degrees C for 1 week . Following thawing and overnight (18-24 h) culture, intact islet recovery was determined by islet counting after dithizone staining . Islet function was assessed by determination of glucose-stimulated insulin secretion in perifusion experiments with Krebs-Ringer bicarbonate buffer, pH 7.4, containing either basal (3.3 mM) or high (16.7 mM) glucose concentrations . The assessment of islet recovery and function of all cryopreserved samples was performed only after thawing and overnight culture (18-24 h) of islets . The mean +/- SEM percent intact islet recovery was higher with PVP compared with DMSO (82 +/- 4.6 vs . 62.7 +/- 3.1%, respectively, p < 0.005, n = 9) . Furthermore, the glucose stimulation index of insulin secretion by islets taken from samples frozen with PEG and PVP, after thawing and overnight culture, was comparable to that of freshly isolated islets, in contrast to DMSO and glycerol . There was no significant difference in intact islet recovery and function between samples frozen with PVP and those frozen with PEG . Samples frozen with DMSO and glycerol had similar results in islet recovery and function . These data show that PVP is a new and potent cryoprotectant for islet cell freezing.

Med J Malaysia, 2003 Dec, 58(5), 777 - 9
A case of severe leptospirosis with pancytopaenia; Bee PC et al.; Pancytopaenia is a rare clinical presentation of severe leptospirosis . We would like to report a case of severe leptospirosis that progressed to pancytopaenia despite initial penicillin therapy . The patient needed a second course of antibiotic with doxycycline to improve his persistent symptoms and cytopaenia . Persistent pancytopaenia in severe leptospirosis and its management were reviewed.

Semin Pediatr Infect Dis, 2004 Apr, 15(2), 109 - 14
Sir Howard Walter Florey--the force behind the development of penicillin; Ligon BL; The development of penicillin was a watershed in the battle against infectious diseases . The primary individuals responsible for its discovery and development were Sir Alexander Fleming, Sir Howard Walter Florey, and Ernst B . Chain, now primary figures in the annals of medical history . The individual who serendipitously "discovered" penicillin was Sir Alexander Fleming . Despite the determination displayed by Fleming, little notice was given to his discovery for more than a decade, and the active substance was not isolated . Finally, in 1939, Florey, along with Chain, led a team of British scientists who successfully manufactured the drug from the liquid broth in which penicillin grows . They, along with Fleming, were given the 1945 Nobel Prize in Physiology or Medicine for their roles in the discovery and development of this agent . This biography focuses on the life and work of Sir Howard Walter Florey.

Biotechnol Prog, 2004 May-Jun, 20(3), 984 - 8
Enantioselective synthesis of phenylacetamides in the presence of high organic cosolvent concentrations catalyzed by stabilized penicillin G acylase . Effect of the acyl donor; Abian O et al.; Immobilization of penicillin G acylase on glyoxyl agarose and its further hydrophilization by physicochemical modification with ionic polymers has made it possible to perform the direct condensation between (+/-)-2-hydroxy-2-phenylethylamine {(+/-)-1} and different acyl donors in the presence of high concentrations of organic cosolvent (up to 90%) in the reaction medium . Using 50 mM phenyl acetic acid and these drastic reaction conditions, too harsh for any other PGA preparation, we have achieved an almost quantitative transformation (more than 99%) of 10 mM (+/-)-1 into the corresponding amide . Remarkably, the enantioselectivity of the enzyme immobilized on the amine was strongly dependent on the acyl donor employed . Thus, using phenylacetic acid (2), the enantioselectivity was almost negligible (1.3 favoring the S isomer), whereas using S-mandelic acid {(S)-4}, the E factor reached a value of 21 (also favoring the S isomer) . By using R-mandelic acid {(R)-4}, we observed a different enantioselectivity (E was 3.6 favoring the R) . At 4 degrees C, the E value reached a value higher than 100 when (S)-4 was used as the acyl donor . The reaction performed under these conditions allowed us to produce (2S,2'S)-N-2'-hydroxy-2'-phenyl)-2-hydroxyphenylacetamide {(2S,2'S)-7} with a diasteromeric excess higher than 98%.

Semin Pediatr Infect Dis, 2004 Jan, 15(1), 58 - 64
Sir Alexander Fleming: Scottish researcher who discovered penicillin; Ligon BL; The discovery and development of penicillin changed the entire direction of approaches to treating infectious diseases and saved the lives of millions of people . Indeed, the development of penicillin was a watershed event in the battle against infectious diseases, and the individual who discovered it, Sir Alexander Fleming, remains a prominent individual in the annals of medical history . This article focuses primarily on the personal life of Alexander Fleming, an individual who had a remarkable diversity of interests and who made many contributions to science and medicine.

Jpn J Ophthalmol, 2004 May-Jun, 48(3), 236 - 42
Cytotoxicity of triamcinolone on cultured human retinal pigment epithelial cells: comparison with dexamethasone and hydrocortisone; Yeung CK et al.; PURPOSE: Triamcinolone acetonide (TA) is a corticosteroid that can be used in the treatment of cystoid macular edema (CME) and other ocular inflammatory conditions . This study aims to investigate the degree of cytotoxic effect of TA on human retinal pigment epithelium (ARPE19 cell line) and to compare the relative toxicity of TA with two other corticosteroids, hydrocortisone (HC) and dexamethasone (DEX), over a range of concentrations and durations of exposure . METHODS: The ARPE19 cell line was cultured and maintained in a 1 : 1 mixture of Dulbecco's modified Eagle's medium and HAMS F12 medium containing 3 mM l-glutamine supplemented with 10% fetal bovine serum, penicillin G, and streptomycin sulfate . Following an initial overnight incubation, corticosteroids (0.01-1 mg/ml) or vehicle (benzyl alcohol, 0.025%), diluted in culture medium, was added to the ARPE19 culture (5000 cells/well) on Day 0 . Subsequently the culture medium containing corticosteroid or vehicle was refreshed daily . After 1, 3, and 5 days, the proliferated amount of cells with and without corticosteroid treatment was determined using a 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay . All samples were read in triplicate, with n = 4 in all cases . The final results were analyzed using analysis of variance . RESULTS: TA, DEX, and HC caused a significant reduction in cell numbers throughout the whole range of concentrations when cells were exposed to them for more than one day . The action of the corticosteroids, apart from TA, was biphasic . There was an initial rise in cell proliferation in the presence of DEX and HC at 0.01-0.1 mg/ml on Day 1 . Log-linear plots of DEX and HC concentrations against percent viability (mean % +/- SD) showed a significantly higher total viable cell percentage versus TA: 120.5 +/- 1.8% and 134.9 +/- 4.1% in the presence of DEX, and 110.0 +/- 15.3% and 118.3 +/- 9.0% in the presence of HC . The LD(50) values of the three corticosteroids show that, regardless of the duration of exposure, TA was the most toxic, with relative toxicity of TA > DEX > HC, equivalent to a ratio of 1.0 : 1.6 : 1.8, after one day of incubation . The vehicle alone had no effect . CONCLUSIONS: The present study demonstrated the degree of cytotoxicity of TA compared with DEX and HC . The results provide a profile of this drug relative to other common corticosteroids . Further studies are planned to characterize its effects and the degree of influence on cells of different ocular regions in order to show the full cytotoxicity of TA.

Thorax, 2004 Jun, 59(6), 522 - 5
Clinical features, aetiology and outcome of empyema in children in the north east of England; Eastham KM et al.; BACKGROUND: The incidence of empyema in children in the UK is increasing . The reason for this is unclear . A prospective study was undertaken to investigate the clinical features, aetiology, and outcome of cases of empyema and parapneumonic effusion presenting to a tertiary paediatric respiratory centre between February 1997 and August 2001 . METHOD: Routine bacterial culture of blood and pleural fluid was performed for 47 cases . Forty three pleural fluid specimens, culture negative for pneumococcus, were analysed for pneumococccal DNA by real time polymerase chain reaction (PCR) . Penicillin susceptibility was determined for DNA positive specimens using complementary PCR assay . Capsular serotype specific antigen detection was by enzyme immunoassay (EIA) using monoclonal antibodies to serotypes 1, 3, 4, 5, 6A, 6B, 7F, 9V, 14, 18C, 19A, 19F, and 23F . Clinical data were obtained from patient notes, supplemented by a postal questionnaire . RESULTS: The median (range) age of the patients was 5.6 (0.6-16.9) years and 70% were male . The median (range) duration of illness before referral to hospital was 5 (0-25) days . Forty five (96%) had received antibiotics before referral; 32 (68%) required decortication and eight (21%) thoracocentesis . Median postoperative stay was 4 days (2-8) . Thirty two (75%) pneumococcal culture negative specimens were pneumococcal DNA positive; 17 (53%) of these were serotype 1 . All were penicillin sensitive . CONCLUSIONS: Pneumococcus is the major pathogen in childhood empyema and serotype 1 is the prevalent serotype . This has implications for vaccine development and immunisation strategy as the current 7-valent pneumococcal conjugate vaccine does not protect against serotype 1.

Sex Transm Dis, 2004 Jun, 31(6), 350 - 2
Magnetic resonance image-reversible findings in a patient with general paresis; Berbel-Garcia A et al.; MATERIAL AND METHODS: We describe clinical, cerebrospinal fluid (CSF), and magnetic resonance imaging (MRI) findings in a patient with general paresis . MRI demonstrated cortical-subcortical atrophy and broad-coalescent high-intensity T2 lesions in right frontotemporal lobes . RESULTS: After intravenous penicillin therapy, the size of these lesions diminished dramatically . That regression correlated with improvement in neuropsychologic test and CSF analysis . CONCLUSION: To our knowledge, this is the first case reported in the literature of MRI-reversible lesions in a patient with general paresis . We suggest that MRI is of prognostic value in patients with general paresis . Severe atrophy, especially in the temporal lobe, could be a marker of bad clinical outcome.

J Agric Food Chem, 2004 Jun 2, 52(11), 3286 - 91
Simple and rapid liquid chromatography-tandem mass spectrometry confirmatory assay for determining amoxicillin and ampicillin in bovine tissues and milk; Bogialli S et al.; A simple specific and rapid confirmatory method for determining the two amphoteric penicillins, that is, amoxicillin and ampicillin, in bovine muscle, liver, kidney, and milk is presented . This method is based on the matrix solid-phase dispersion technique with hot water as extractant followed by liquid chromatography (LC)-tandem mass spectrometry . With this instrumentation, the selected reaction monitoring acquisition mode with two fragmentation reactions for each analyte was adopted . After acidification and filtration of the aqueous extracts, 25 microL of the tissue final extracts and 50 microL of the milk final extract were injected into the LC apparatus . Absolute recovery of the two analytes in any biological matrix at the 50 ppb level in tissues and the 4 ppb level in milk was 74-95% with relative standard deviations (RSDs) of no larger than 9% . When penicillin V was used as surrogate internal standard, relative recovery of the targeted compounds present in bovine tissues and milk at, respectively, 25 and 2 ppb levels ranged between 100 and 106% with RSDs of no larger than 11% . When fractionation of analytes by using a short chromatographic run was attempted, remarkable signal weakening for the two analytes was experienced . This effect was traced to polar endogenous coextractives eluted in the first part of the chromatographic run that interfered with the gas-phase ion formation of the two penicillins . Slowing the chromatographic run eliminated this unwelcome effect . Limits of quantification of the two analytes in bovine milk were estimated to be <1 ppb, whereas amoxicillin and ampicillin could be quantified in bovine tissues down to 3.1 and 0.8 ppb levels, respectively.

J Biol Chem, 2004 Aug 6, 279(32), 33253 - 62 Epub 2004 May 24.
Regulation of penicillin G acylase gene expression in Escherichia coli by repressor PaaX and the cAMP-cAMP receptor protein complex; Kim HS et al.; The pga gene of Escherichia coli W ATCC11105 encodes a penicillin G acylase whose expression is regulated at both the transcriptional and post-transcriptional level . In this work we have shown that PaaX is the repressor of pga expression, and we have identified its binding consensus as TGATTC(N27)GAATCA . We conclude that the process of "PAA induction" actually involves relief of pga from repression by PaaX . Other features of the pga promoter have also been characterized . (i) It has a native class III cAMP-receptor protein (CRP)-dependent promoter with two CRP-binding sites . (ii) The downstream CRP-binding site II has higher affinity . (iii) Binding of cAMP-CRP to both sites (I + II) is required for maximal expression . We have also shown that the PaaX-binding site overlaps with the CRP-binding site I . This implies that PaaX and the cAMP-CRP compete for binding to the region around the CRP-binding site I and therefore have antagonistic effects on pga expression.

FEMS Microbiol Lett, 2004 Jun 1, 235(1), 117 - 24
Identification Leptospira santarosai serovar shermani specific sequences by suppression subtractive hybridization; Hsieh WJ et al.; In Taiwan, leptospirosis is caused mainly by Leptospira santarosai serovar shermani . Suppression subtractive hybridization was employed to isolate DNA fragments present in pathogenic L . santarosai serovar shermani but absent in non-pathogenic L . biflexa serovar patoc . Analysis of 23 subtracted DNA clones revealed 25 gene fragments by BLASTX program . Eight clones showed similarity to transposase genes and three clones displayed homology with either translation or metabolism related genes . Four clones were similar to outer membrane protein, penicillin-binding protein, CreD-like protein and the protein of two-component signal transduction system, respectively . One clone had TPR repeat domain and five clones had significant similarity with hypothetical proteins of unknown functions . The remaining four clones exhibited no homology with any known genes . These results indicate that subtractive hybridization can successfully identify genes that are absent from the non-pathogenic Leptospira and provide a starting point for clarifying the differential genes expression between pathogenic and non-pathogenic Leptospira species.

Biotechnol Appl Biochem, 2004 Jun, 39(Pt 3), 285 - 91
Mannan-penicillin G acylase neoglycoproteins and their potential applications in biotechnology; Masarova J et al.; Mannan-penicillin G acylase neoglycoproteins were prepared by the conjugation of Saccharomyces cerevisiae mannan with enzyme penicillin G acylase using the reductive amination method . Eight neoglycoproteins preparations were obtained after gel chromatography . The preparations contained from 42 to 67% (w/w) saccharides and their molar masses varied from 283 to over 1000 kDa . Significant biospecific interaction of separated fractions with the lectin concanavalin A was evaluated by the precipitation and sorption method (equilibrium constants) and further characterized using surface plasmon resonance to determine kinetic association and dissociation constants . K (D) was determined over the range 10(-7) M . High-molar-mass preparations appeared to be more suitable for preparation of stable and active complexes with concanavalin A for prospective use as a penicillin G acylase biocatalyst in enzyme reactors . The enzyme stability of such complexes was significantly increased compared with the original neoglycoprotein . Lower-molar-mass preparations were more suitable for applications such as biocatalysts in bioanalytical devices.

Eur J Biochem, 2004 Jun, 271(11), 2272 - 9
Kinetic studies and molecular modelling attribute a crucial role in the specificity and stereoselectivity of penicillin acylase to the pair ArgA145-ArgB263; Guncheva M et al.; Kinetic experiments with a substrate series of phenylacetyl-arylamides reveal that at least one polar group in the amine moiety is required for the proper orientation of the substrate in the large nucleophile-binding subsite of penicillin acylase of Escherichia coli . Quantum mechanical molecular modelling of enzyme-substrate interactions in the enzyme active site shows that in the case of substrates lacking local symmetry, the productive binding implies two nonsymmetrical arrangements with respect to the two positively charged guanidinium residues of ArgA145 and ArgB263 . This indicates a crucial role of the specified arginine pair in the substrate- and stereoselectivity of penicillin acylase.

J Am Soc Mass Spectrom, 2004 Jun, 15(6), 803 - 22
Development of an LC-MALDI method for the analysis of protein complexes; Zhen Y et al.; In this study, a two-dimensional LC-MALDI-TOF/TOF method has been developed for analyzing protein complexes . In our hands, the method has proven to be an excellent strategy for the analysis of protein complexes isolated in pull-down experiments . This is in part because the preservation of the chromatographic separation on a MALDI target yields an "unlimited" amount of time to obtain MS/MS spectra, making it possible to probe more deeply into complex samples . A brief statistical analysis was performed on the data obtained from the LC-MALDI-TOF/TOF system in order to better understand peptide fragmentation patterns under high-energy collision conditions . These statistical analyses provided some insight into how to evaluate the quality and accuracy of the database search results derived from the TOF/TOF-based analysis . The potential of the method was demonstrated by the successful identification of all the known penicillin-binding proteins in E . coli isolated using a drug-based pull-down with ampicillin as the bait . The performance of the LC-MALDI-TOF/TOF system was compared with that of an equivalent 2D LC-ESI-MS/MS approach, in the analysis of a protein bait-based pull-down . Regardless of the number of peptides identified in the ESI versus MALDI approach, the two approaches were found to be complementary . When the data is merged at the peptide level, the combined result gives higher Mascot scores and an overall higher confidence in protein identification than with either approach alone.

Drug Saf, 2004, 27(6), 393 - 410
Prevention of anaphylactic reactions to anaesthetic drugs; Fisher MM et al.; Although screening tests to prevent anaphylaxis during anaesthesia have been advocated, such tests are unlikely to have significant impact on reducing the incidence of anaphylaxis during anaesthesia . This is due to the low prevalence of the disease, the diversity of drugs used in anaesthesia and the incidence of false positive and negative tests . The suggested risk factors of allergy, i.e . atopy, asthma, family history, female sex, previous exposure, vasectomy, use of zinc protamine sulfate insulin and allergy to cosmetics, eggs, fish and non-anaesthetic drugs are not valid . Although all have theoretical or real associations with anaphylaxis during anaesthesia the majority of patients with such a history undergo uneventful anaesthesia . Fruit allergy, anaphylaxis to cephalosporins and penicillin, barbiturate allergy, gelatin allergy and allergy to metabisulphite and eggs require consideration in avoiding particular drugs . The incidence of anaesthetic anaphylaxis can be reduced by avoiding latex exposure in patients with spina bifida or latex allergy, and preventing second reactions in patients with a history of anaphylaxis, or major undiagnosed or undocumented adverse events during anaesthesia . Determining the cause of an adverse event and the drug responsible, and adequately communicating those findings can reduce second reactions . Avoiding neuromuscular blocking drugs (NMBDs) in patients who have reacted to an NMBD, and use of non-intravenous techniques should also reduce the incidence of second reactions . Desensitisation, and blocking with monovalent quaternary ammonium compounds may allow improved safety of NMBDs and pretreatment with antihistamines and corticosteroids may block or ameliorate the severity of reactions, but there is currently little evidence to support their routine use.

J Agric Food Chem, 2004 May 19, 52(10), 2791 - 6
Determination of beta-lactams in milk using a surface plasmon resonance-based biosensor; Gustavsson E et al.; Two surface plasmon resonance (SPR)-based biosensor assays for detection of beta-lactam antibiotics in milk are reported . The assays are based on the enzymatic activity of a carboxypeptidase converting a 3-peptide into a 2-peptide, a reaction that is inhibited in the presence of beta-lactams . Antibodies were used to measure either the amount of formed enzymatic product or the amount of remaining enzymatic substrate . Both assays detected different beta-lactams at or below European maximum residue limits (MRLs), and the detection limit for penicillin G was 1.2 microg/kg and 1.5 microg/kg for the 2- and 3-peptide assays, respectively . The precision (CV) was < 5%, both within and between assays at the penicillin G MRL (4 microg/kg) . The biosensor results obtained upon analysis of incurred milk samples were compared with results obtained by liquid chromatography (HPLC), and the method agreements were, in general, good.

J Chromatogr B Analyt Technol Biomed Life Sci, 2004 Jun 15, 805(2), 365 - 9
Determination of paraldehyde by gas chromatography in whole blood from children; Githiga IM et al.; A rapid, sensitive and selective gas chromatographic method with flame ionization detection was developed for the determination of paraldehyde in small blood samples taken from children . Whole blood samples (300 microl) collected in a 3 ml Wheaton glass sample vial were spiked with acetone (internal standard: 15 ng) followed by addition of concentrated hydrochloric acid . The mixture was heated in the sealed airtight sample vial in a water bath (96 Celsius; 5 min) to depolymerize paraldehyde to acetaldehyde . A 2 ml aliquot of the headspace was analyzed by gas chromatography with flame ionization detector using a stainless steel column (3 m x 4 mm i.d.) packed with 10% Carbowax 20 M/ 2% KOH on 80/100 Chromosorb WAW . Calibration curves were linear from 1.0-20 microg (r2>0.99) . The limit of detection was 1.5 microg/ml, while relative mean recoveries at 2 and 18 microg were 105.6 +/- 8.4 and 101.2 +/- 5.9%, respectively (n = 10 for each level) . Intra- and inter-assay relative standard deviations at 2, 10 and 18 microg were <15% . There was no interference from other drugs concurrently used in children with severe malaria, such as anticonvulsants (diazepam, phenytoin, phenobarbitone), antipyretics/analgesics (paracetamol and salicylate), antibiotics (gentamicin, chloramphenicol, benzyl penicillin) and antimalarials (chloroquine, quinine, proguanil, cycloguanil, pyrimethamine and sulfadoxine) . The method was successfully applied for pharmacokinetic studies of paraldehyde in children with convulsions associated with severe malaria.

Protein Sci, 2004 Jun, 13(6), 1677 - 83 Epub 2004 May 07.
Production of a fully functional, permuted single-chain penicillin G acylase; Flores G et al.; Penicillin G acylase (PGA) is a heterodimeric enzyme synthesized as a single-polypeptide precursor that undergoes an autocatalytic processing to remove an internal spacer peptide to produce the active enzyme . We constructed a single-chain PGA not dependent on autoproteolytic processing . The mature sequence of the beta-domain was expressed as the N terminus of a new polypeptide, connected by a random tetra-peptide to the alpha-domain, to afford a permuted protein . We found several active enzymes among variants differing in their linker peptides . Protein expression analysis showed that the functional single-chain variants were produced when using a Sec-dependent leader peptide, or when expressed inside the bacterial cytoplasm . Active-site titration experiments showed that the single-chain proteins displayed similar k(cat) values to the ones obtained with the wild-type enzyme . Interestingly, the single-chain proteins also displayed close to 100% of functional active sites compared to 40% to 70% functional yield usually obtained with the heterodimeric protein.

Biomacromolecules, 2004 May-Jun, 5(3), 852 - 7
Co-aggregation of penicillin g acylase and polyionic polymers: an easy methodology to prepare enzyme biocatalysts stable in organic media; Wilson L et al.; A novel type of biocatalyst that combines the good properties of cross-linked enzyme aggregates (CLEAs) and hydrophilic microenvironments has been developed . Dextran sulfate- and polyethyleneimine-coated CLEAs of penicillin acylase (CLEA-GDP) were prepared by adding the polymers of different sizes before the precipitation stage of the enzyme . This study presents the development and optimization of a protocol to produce such a biocatalyst using penicillin acylase as a model . Experiments show that CLEA-GDPs have a highly increased stability in organic media . The average half-life of the preparations was much higher than standard CLEA without a microenvironment (CLEA-G), (e.g., more than 25-fold) in the presence of dioxane . However, their thermal stability was not increased, which leads to the conclusion that the stability of CLEA-GDPs in organic media is due to the hydrophilic microenvironment that surrounds the protein enzyme more than to a conformational stiffening effect . This is further supported by solvation experiments that show a preferential hydration of CLEA when polymers are used to coat the enzyme . CLEA-GDPs are clearly better than other biocatalysts in terms of solvent stability.

Toxicol In Vitro, 2004 Aug, 18(4), 511 - 25
Discriminative power of an assay for automated in vitro screening of teratogens; Walmod PS et al.; Screening for potential teratogenicity of 20 test compounds was performed using a computerised microscope workstation for determination of cytotoxicity, proliferation and morphology of fibroblastoid murine L929-cells . The test compounds, which were divided into four classes according to teratogenicity were: 5-bromo-2(')-deoxyuridine, 6-aminonicotinamide, acrylamide, boric acid, D-(+)-camphor, dimethadione, dimethyl phthalate, diphenhydramine, hydroxyurea, isobutyl-ethyl-valproic acid, lithium chloride, methyl mercury chloride, methotrexate, methoxyacetic acid, penicillin G, all-trans-retinoic acid, pentyl-4-yn-valproic acid, saccharin, salicylic acid and valproic acid . All compounds, with the exception of dimethadione inhibited proliferation in a linear dose-dependent manner, and there were statistically significant compound class-dependent differences between the IC(50)-values for the compounds (p<0.0374), the strongest teratogens being the most potent . Furthermore, the average efficacies (maximum relative change) for 10 parameters describing cell morphology exhibited statistically significant compound class-dependent differences (p<0.0001), the class I and II compounds exhibiting significantly lower efficacies than the class III and IV compounds (p<0.01) . Thus, test compounds affected both the proliferation and morphology of L-cells in manner demonstrating a general relationship with the teratogenic potency of the compounds . However, the moderate teratogens dimethadione and lithium chloride only had minor effects on the morphology and proliferation of the cells whereas the non-teratogen diphenhydramine had effects on both proliferation and morphology comparable to the strong teratogens.

Biotechnol Bioeng, 2004 Jun 5, 86(5), 558 - 62
Encapsulation of crosslinked penicillin G acylase aggregates in lentikats: evaluation of a novel biocatalyst in organic media; Wilson L et al.; The encapsulation of crosslinked enzyme aggregates (CLEA) of penicillin G acylase into a very rigid polymeric matrix based on polyvinyl alcohol (LentiKats) has been used successfully to improve the inadequate mechanical properties of CLEA . This encapsulation decreased CLEA activity by only around 40% . As compensation, a significant improvement in the stability of the CLEA in the presence of organic solvents was detected . This could be related to the highly hydrophilic environment inside the LentiKats biocatalysts: Partition experiments showed that the concentration of dioxane inside LentiKats was lower than in the reaction medium . In fact, thermal stability was about the same as in the corresponding CLEA . This permitted great improvement in the reaction rate for thermodynamically controlled synthesis of a model antibiotic (using phenylacetic acid and 7-amino-deacetoxycefalosporanic acid) . Even more importantly, yields could be improved by using LentiKats-encapsulated CLEA, very likely by a favorable product/substrate partition . Thus, this very simple technique not only provides an efficient technique for solving the mechanical stability problem associated with CLEA, but also greatly improves the behavior of CLEA in organic media .

J Biotechnol, 2004 May 27, 110(2), 119 - 36
Enhanced process monitoring of fed-batch penicillin cultivation using time-varying and multivariate statistical analysis; Lee JM et al.; On-line monitoring of penicillin cultivation processes is crucial to the safe production of high-quality products . In the past, multiway principal component analysis (MPCA), a multivariate projection method, has been widely used to monitor batch and fed-batch processes . However, when MPCA is used for on-line batch monitoring, the future behavior of each new batch must be inferred up to the end of the batch operation at each time and the batch lengths must be equalized . This represents a major shortcoming because predicting the future observations without considering the dynamic relationships may distort the data information, leading to false alarms . In this paper, a new statistical batch monitoring approach based on variable-wise unfolding and time-varying score covariance structures is proposed in order to overcome the drawbacks of conventional MPCA and obtain better monitoring performance . The proposed method does not require prediction of the future values while the dynamic relations of data are preserved by using time-varying score covariance structures, and can be used to monitor batch processes in which the batch length varies . The proposed method was used to detect and identify faults in the fed-batch penicillin cultivation process, for four different fault scenarios . The simulation results clearly demonstrate the power and advantages of the proposed method in comparison to MPCA.

Int J STD AIDS, 2004 May, 15(5), 352 - 4
Audit of the management of early syphilis at North Manchester General Hospital; Kingston MA et al.; The city of Manchester has seen a sustained increase in reported cases of early (infectious) syphilis since the late 1990s . We audited the management of patients presenting with early syphilis to North Manchester General Hospital, with reference to the UK national guidelines . Between January 1999 and December 2001 72 cases of early syphilis were identified . Most (90%) occurred in men who have sex with men, 50% of whom were HIV-positive . Serology and polymerase chain reaction testing of lesions were useful diagnostic tests . Treatment regimens followed the national guidelines in 63% of cases, with adherence to the guidelines improving as the outbreak continued . The majority of patients were treated with intramuscular penicillin (78%), with only three discontinuing this treatment due to side effects . Only 4% of sexual contacts identified were traced and screened, an indication of high levels of both anonymous sex and partner change in this group.

Rev Prat, 2004 Feb 29, 54(4), 396 - 9
{When to think about neurosyphilis?}; Grivois JP et al.; The clinical spectrum of neurosyphilis is large . Serologic tests for syphilis are commonly indicated in diseases involving the central nervous system . The diagnosis of syphilis relies on epidemiological, clinical and biological grounds (cerebrospinal fluid abnormalities and RPR test) . The treatment of neurosyphilis is still penicillin G.

Rev Prat, 2004 Feb 29, 54(4), 392 - 5
{Syphilis and pregnancy}; Mandelbrot L et al.; Consequences of syphilis for mother, pregnancy, fetus and child are considerable, but preventable . Serological screening must be offered at the first prenatal visit, using both a treponemal (eg . TPHA) and a non treponemal (eg . VDRL or RPR) test . When the results are compatible with any type of active syphilis, treatment is required . The treatment of choice is penicillin: benzathine penicillin G, 2.4 million units intramuscular, repeated one week later, and most authors recommend a third dose if a late latent syphilis is suspected, or in case of coinfection with HIV . Women with a proven penicillin allergy can be desensitized . Alternative therapies, such as macrolids, are less well evaluated . Follow-up during and after therapy must not be neglected . In case of Jarisch-Herxheimer reaction, the mother should be managed on an inpatient basis, and the fetus carefully monitored . The VDRL should be repeated (usually every trimester), and therapy be renewed if there is not a significant decrease in titer . The fetus should be followed by serial ultrasound examinations . Finally, the child must be followed up clinically and biologically, and treated in case of congenital syphilis . The residual risk of adverse outcome is increased in case of reinfection, lack of maternal therapy or incomplete treatment, or when diagnosis and therapy are performed late in pregnancy.

Surg Today, 2004, 34(5), 447 - 9
Thoracic actinomycosis as a cause of superior vena cava syndrome: report of a case; Kotoulas C et al.; We report an unusual case of superior vena cava syndrome (SVCS) caused by thoracic actinomycosis in a 35-year-old man . The patient presented with a mediastinal mass and the diagnosis was confirmed by a right exploratory thoracotomy . Treatment with penicillin for a 15-month period resulted in a reduction in the size of the mediastinal mass and improvement of his clinical symptoms.

J Allergy Clin Immunol, 2004 Apr, 113(4), 764 - 70
Represcription of penicillin after allergic-like events; Apter AJ et al.; OBJECTIVE: We sought to determine the frequency of represcription of penicillin to individuals with penicillin allergy and the risk of a second reaction in those who had a previous reaction . METHODS: A retrospective cohort study was conducted within the UK General Practice Research Database . All patients who had received a prescription for penicillin were identified . Within that source population, records of patients who had received at least 2 prescriptions for penicillin at least 60 days apart were selected and examined for allergic-like (hypersensitivity) events on the day of or within 30 days after a prescription . RESULTS: At least one prescription for penicillin was given to 3,375,162 patients . Of 6212 (0.18%) patients who experienced an allergic-like event after the initial prescription, 48.5% were given a second prescription compared with 59.8% of those without an initial allergic-like event (risk ratio, 0.81; 95% CI, 0.79-0.83) . Two or more prescriptions for penicillin were given to 2,017,957 patients . Three thousand fourteen (0.15%) patients experienced an allergic-like event after the first prescription, and 57 (1.89%) of those had another event after the second prescription . The unadjusted odds ratio of an allergic-like event after the second prescription for those who experienced an allergic-like event after the first prescription, compared with those who had no initial event was 11.2 (95% CI, 8.6-14.6) . Adjusting for confounding had no substantive effect on this result . CONCLUSION: The risk of an allergic-like event after penicillin is markedly increased in those who have had a prior event, although the absolute difference is small (1.72%) . Represcription of penicillin to such patients is more frequent than anticipated.

J Biotechnol, 2004 May 13, 110(1), 11 - 9
Biospecific immobilization of mannan-penicillin G acylase neoglycoenzyme on Concanavalin A-bead cellulose; Mislovicova D et al.; The matter of this work was to evaluate possibilities of biospecific immobilization of synthetic mannan-penicillin G acylase neoglycoconjugate on Concanavalin A support . The conjugate containing 37% (w/w) of yeast mannan was prepared . Significant biospecific interaction of this neoglycoenzyme with Con A was confirmed by precipitation method . The biospecific sorption of conjugate was investigated using Concanavalin A-triazine bead celluloses MT-100 with different content of Con A (from 1.4 to 9.8 mgCon A/gwet support) . The results obtained under optimal conditions were compared with those from covalent immobilization of PGA . The sorbent capacity was observed higher for covalent binding of enzyme . On the other hand, the biospecifically immobilized neoglycoenzyme retained a greater amount of initial activity . The maximum amount of 6.6mgimmobilizedneoglycoenzyme/gwet Con A-sorbent (18.1 U/g) was achieved . The amount as well as activity of immobilized mannan-penicillin G acylase was increased by its two multiple layering on surface of sorbent (10.1mg, respectively, 23.5 U/gwet sorbent) . Determined storage and operational (using flow calorimetric method) stabilities of biospecifically immobilized enzyme, were similar, possibly somewhat higher that those of covalent bound penicillin G acylase.

J Cell Physiol, 2004 Jun, 199(3), 460 - 9
Three novel hormone-responsive cell lines derived from primary human breast carcinomas: functional characterization; Vazquez SM et al.; Human breast cancer primary cultures are useful tools for the study of several aspects of cancer biology, including the effects of chemotherapy and acute gene expression in response to different hormonal/chemotherapy treatments . The present study reports the conditions for primary culture of breast cancer samples from untreated patients and the most effective collagenization method to dissociate human samples consisting in an overnight incubation with 1 mg/ml types II or IV collagenase and further incubation in DMEM:F12 (1:1) medium supplemented with glutamine, bovine insulin, penicillin-streptomycin, HEPES, estradiol, cortisol (F), tri-iodothyronine (T(3)), transferrine (TR), and 10% fetal calf serum (FCS) . These conditions proved to be appropriate for both primary culture and the development of stable cell lines . Of the seven cell lines obtained, three fast growing and estrogen receptor (ER)+/progesterone receptor (PgR)+/EGF receptor (EGFR)+ have been characterized . The cells are able to grow both in soft agar and in nude mice, and express cytokeratins, all parameters characteristic of malignant epithelial cell lines . The cells also exhibit an increased proliferation rate in the presence of estradiol, progesterone, and EGF, suggesting the presence of the corresponding receptors . The mRNA expression of type alpha- and beta-ER as well as EGFR, was confirmed by RT-PCR . In conclusion, the novel cell lines described, arose from primary tumors and are sensitive to estradiol, progesterone, and EGF . This not only expands the repertoire of breast cancer cells available as potentially useful tools for examining most parameters in breast cancer "in vitro", but also provides unique new models to explore the complex regulation by steroids as well as growth factors in such cells .

Biosens Bioelectron, 2004 Jun 15, 19(11), 1445 - 56
Electrochemical synthesis and impedance characterization of nano-patterned biosensor substrate; Takhistov P; The nano-porous anodic aluminum oxide has been used as a substrate material for enzymatic biosensor operating in aqueous solutions . Nano-scale porous structure was formed by electrical anodization in an acid solution . By changing anodization conditions, such as electrolyte concentration, temperature, and anodization time, the ordered hexagonal porous structure with well-controlled pore size and depth can be obtained . Nano-porous alumina substrate with adsorbed enzymes was used as an enzyme electrode and pH sensor . The pH changes are driven by the enzymatic reactions, e.g . penicillin G hydrolysis to form penicilloic acid in the presence of penicillinaze . The advantage of physical adsorption used to bound penicillinaze, the model enzyme in this work, to the porous structure, is that usually no reagents are required and only a minimum of "activation" or clean-up steps . Adsorption tends to be less disruptive to enzyme proteins than chemical attachment . Due to the increased active sensor area, the immobilization of enzymes has been enhanced, which in turn improved the electrode's sensitivity . To characterize the interactions of enzymes with nano-porous alumina oxide, electrochemical impedance spectroscopy (EIS) was used.

J Oral Maxillofac Surg, 2004 Apr, 62(4), 431 - 4
Treatment of chronic sialadenitis by intraductal penicillin or saline; Antoniades D et al.; PURPOSE: We sought to describe the treatment of chronic sialadenitis by intraductal penicillin or saline . PATIENTS AND METHODS: The study group consisted of 32 males and 23 females with chronic submandibular sialadenitis aged 12 to 65 years and 16 males and 11 females with chronic parotitis aged 8 to 65 years who were treated by intraductal instillation of penicillin or saline . RESULTS: In the patients with submandibular sialadenitis, 44 patients treated with penicillin and 11 treated with saline became symptom free; symptoms recurred in 3 treated with penicillin, of whom 2 became symptom free after further instillations and 1 after removal of a sialolith at the ductal orifice; and follow-up of 22 patients verified that 18 treated with penicillin and 4 with saline had been symptom free for 1 to 15 years and 1 to 3 years, respectively . In the patients with parotitis, 18 patients treated with penicillin, 8 treated with saline, and 1 treated with both became symptom free; symptoms recurred in 1 treated with penicillin and 1 with saline, both of whom became symptom free after further instillations; and follow-up of 15 patients verified that 11 treated with penicillin, 3 with saline, and 1 with both had been symptom free for 1 to 14 years, 2 to 12 years, and 3 years, respectively . CONCLUSION: The intraductal instillation of penicillin or saline is a simple and surprisingly successful technique for the treatment of chronic sialadenitis.

Heart . 2004 May;90(5):e27.
Cardiac actinomycosis in a patient presenting with acute cardiac tamponade and a mass mimicking pericardial tumour; Janoskuti L et al.; A case of pericardial actinomycosis mimicking a pericardial tumour is reported . After the appearance of non-specific subpleural pulmonary nodules, a 48 year old woman presented with fever and clinical signs of pericardial tamponade . Subxiphoid pericardiotomy yielded a culture negative fluid and inflammatory reactive histopathology in the pericardial biopsy specimen . Because of suspected infection cefamandole was administered for 10 days and the patient became afebrile . The pericardial effusion recurred with no clinical signs two weeks later . Steroid medication resulted in rapid regression of the pericardial effusion . Subsequent echocardiography controls showed a tumour-like pericardial mass, confirmed by cardiac magnetic imaging . Surgical exploration led to the final histological diagnosis of actinomycosis . After high dose and long term penicillin G treatment the patient recovered fully with no recurrence during two years' follow up.

J AOAC Int, 2004 Jan-Feb, 87(1), 45 - 55
Confirmatory determination of six penicillins in honey by liquid chromatography/electrospray ionization-tandem mass spectrometry; Wang J; A confirmatory method for 6 penicillin antibiotics (amoxicillin, ampicillin, penicillin G, oxacillin, cloxacillin, and dicloxacillin) in honey is presented that allows determination and confirmation of identity of the antibiotics at trace levels . The method includes the use of a stable isotope-labeled internal standard benzyl (d7-phenyl) penicillate and removal of sugar and other substances by solvent and solid-phase extraction . The honey extracts are then analyzed for penicillin residues by liquid chromatography/electrospray ionization-tandem mass spectrometry . Mass spectral acquisition was achieved in an electrospray positive ion mode by applying multiple reaction monitoring of 2 or 3 fragment ion transitions to provide a high degree of sensitivity and specificity . Typical recoveries of 6 penicillins at fortification levels of 6, 16, 40, and 80 microg/kg ranged from 51.4 to 132.9% . The recoveries varied with the individual penicillins and were affected by different honey matrixes . The ion ratios were consistent and could be used for confirmation of identity of the penicillins . The method limits of detection (microg/kg) were 0.25 for amoxicillin, 0.19 for ampicillin, 0.068 for penicillin G, 0.028 for oxacillin, 0.052 for cloxacillin, and 0.085 for dicloxacillin . The method limits of confirmation (microg/kg) were 0.44 for amoxicillin, 0.52 for ampicillin, 0.23 for penicillin G, 0.14 for oxacillin, 0.14 for cloxacillin, and 0.15 for dicloxacillin when a sample size of 5 g honey was used.

Biotechnol Bioeng, 2004 May 5, 86(3), 273 - 6
A new, mild cross-linking methodology to prepare cross-linked enzyme aggregates; Mateo C et al.; Cross-linked enzyme aggregates (CLEAs) were prepared from several enzymes (penicillin G acylase, hydroxynitrile lyase, alcohol dehydrogenase, and two different nitrilases) by precipitation and subsequent cross-linking using dextran polyaldehyde . In most cases, higher immobilization yields were obtained using the latter cross-linker as compared with the commonly used glutaraldehyde . Active site titration of penicillin acylase CLEAs showed that the higher activity originated from a significantly lower loss in active sites using dextran polyaldehyde as a cross-linking agent . It is proposed that macromolecular cross-linkers are too large to penetrate the protein active site and react with catalytically essential amino acid residues .

Infect Dis Clin North Am, 2004 Mar, 18(1), 101 - 10
The impact of syphilis on humankind; Tramont EC; Until the advent of penicillin and the antibiotic era in the mid-20th century, syphilis was a prevalent disease, infecting between 8% and 14% of the population living in urban areas . The disease progressed to a chronic illness in up to 25% of patients, and its late neurologic manifestations had a profound affect on Western history when it infected societal leaders; on societal morays as a means to curb the disease; and on public health practices . Syphilis was a major impetus for the advent of strict informed consent policies.

Sex Transm Dis, 2004 Mar, 31(3), 196 - 9
Relapse of secondary syphilis after benzathine penicillin G: molecular analysis; Myint M et al.; BACKGROUND AND OBJECTIVES: It is difficult to distinguish between relapse and reinfection in patients who develop a second episode of syphilis after treatment . GOAL: The goal of this study was to use molecular methods to distinguish between relapse and reinfection in a patient with recurrent secondary syphilis . STUDY DESIGN: Treponema pallidum tprK sequences were amplified from cerebrospinal fluid (CSF), skin, and blood from the initial presentation and from blood from the second presentation . Neighbor-joining clustering analysis was performed for deduced tprK sequences from the case patient and for sequences derived from blood and CSF of a different patient with secondary syphilis . RESULTS: The case patient's tprK sequences from both episodes of syphilis clustered together with a high degree of similarity . CONCLUSION: Our patient likely relapsed despite treatment.

Eukaryot Cell, 2004 Apr, 3(2), 527 - 35
LaeA, a regulator of secondary metabolism in Aspergillus spp; Bok JW et al.; Secondary metabolites, or biochemical indicators of fungal development, are of intense interest to humankind due to their pharmaceutical and/or toxic properties . We present here a novel Aspergillus nuclear protein, LaeA, as a global regulator of secondary metabolism in this genus . Deletion of laeA (DeltalaeA) blocks the expression of metabolic gene clusters, including the sterigmatocystin (carcinogen), penicillin (antibiotic), and lovastatin (antihypercholesterolemic agent) gene clusters . Conversely, overexpression of laeA triggers increased penicillin and lovastatin gene transcription and subsequent product formation . laeA expression is negatively regulated by AflR, a sterigmatocystin Zn2Cys6 transcription factor, in a unique feedback loop, as well as by two signal transduction elements, protein kinase A and RasA . Although these last two proteins also negatively regulate sporulation, DeltalaeA strains show little difference in spore production compared to the wild type, indicating that the primary role of LaeA is to regulate metabolic gene clusters.

Acta Dermatovenerol Croat, 2004, 12(2), 96 - 8
Traumatic purpuric penile ulcer; Witkowski JA et al.; A 33-year-old man presented with a history of a penile ulcer of four days' duration . He was immediately treated with 2.4 million IU of benzathine penicillin IM and tested for syphilis, but subsequently proved non-reactive . He was already receiving doxycycline BID from another physician for this nonspecific genital ulcer and minocycline for acne . Past medical history revealed periodic flares of hidradenitis suppurativa, limited to the buttocks and inguinal region; acne, involving the face and back; and angiokeratoma of the scrotum . He had no known drug allergies, nor had he admitted to taking any other medicaments . Examination revealed an 8 x 15 mm irregularly shaped, shallow, tender ulcer over a larger purpuric base and involving part of the corona and the distal portion of the shaft . No inguinal adenopathy or buboes could be found on palpation . The patient was placed on a cream containing 3% iodochlorhydroxyquin 1% hydrocortisone . By the end of two weeks of therapy, the lesion had healed with no residual discoloration . Subsequently, the patient revealed that he masturbated daily, rubbing his penis back and forth on the bed sheet while lying prone on the bed . Eleven months later, he consulted us again for a new purpuric penile ulcer, because he had begun to masturbate in his usual fashion . The ulcer healed within several days, and there were no sequellae.

Pharmacoepidemiol Drug Saf, 1997 Oct, 6 Suppl 3, S61 - 9
In vitro diagnosis of drug allergy . Assessment of the chromatin activation test (CAT); De Sousa Pinto JM et al.; A controlled in vitro study was performed on people suspected to be allergic to one or more drugs by using the chromatin activation test . This test is based on the decrease of the nuclear lymphocyte birefringence induced by stimulation with allergens . A group of 70 patients with suspected drug hypersensitivity and a control group of 37 persons were studied . Fifty-two patients were evaluated by clinical criteria and the cause-effect relationship classified as definitive, probable, possible, improbable and not related . Previously, 18 patients had been considered allergic to penicillin by means of RAST and/or skin tests . The chromatin activation of the peripheral lymphocytes was determined by comparing the nuclear birefringence of cells incubated with different sequential drug concentrations, with that detected in cells incubated without drugs, employing a polarized light microscope . When possible, the oral challenge was carried out in the negative cases . In 123 tests made in the patient group, 45 were positive and distributed as follows: in the cases of definitive imputability (83.3%), probable (60.5%), possible (22.7%), improbable (0%) and not related (0%); in the cases with RAST and/or skin positive tests (33.3%) . Thirty-two of 36 oral tests confirmed those results . Among 50 tests performed in the control group, two (4%) were false positive . These results point to the usefulness of this test in the diagnosis of drug allergy .

Pharmacoepidemiol Drug Saf, 1998 Mar, 7(2), 99 - 106
Drugs and colon cancer; Friedman GD et al.; In a case-control study of colon cancer conducted in three geographic regions of the United States, 1993 case subjects and 2410 control subjects were interviewed . In addition to queries regarding other known or suspected risk factors, subjects were asked about their use of eight drugs or drug groups . Two of these, aspirin and other nonsteroidal anti-inflammatory drugs (NSAIDs), have been inversely associated with risk in other studies . Three others--asthma medications, digitalis preparations, and phenmetrazine--were positively associated and the last three--diazepam, penicillin, and phenformin--were negatively associated with risk of colon cancer in an earlier study that screened pharmaceuticals for possible carcinogenic effects . Reported use of aspirin and NSAIDs were both inversely related to risk with essentially the same odds ratios (0.7, 95% confidence interval 0.6-0.8) for both drugs in both univariate and multivariate analyses controlling for use of each other and for other colon cancer risk factors . Subdivision by age at starting the drug, duration of use, latency interval, sex, race, family history of colon cancer, or proximal versus distal cancer revealed no substantial differences among subgroups for either aspirin or NSAIDs, but reduced risk was associated primarily with recent aspirin use . Phenformin showed a strong positive association but the data concerning this drug appeared to be inaccurate . The other drugs and drug groups showed essentially no association with colon cancer risk .

J Chromatogr A, 2004 Apr 2, 1032(1-2), 265 - 72
Application of capillary electrophoresis to the determination of various benzylpenicillin salts; Pajchel G et al.; The application of capillary electrophoresis for separation of benzylpenicillin, procaine, benzathine and clemizole was investigated . Phosphate-borate buffer supplemented with sodium dodecyl sulphate 14.4 g/l and electrophoresis voltage 18 kV seem to provide optimal conditions for micellar electrokinetic chromatographic assay of penicillin salts . This method is selective and precise . The results obtained from CE method recovery assay (above 98% for all but procaine-97% substances) and from determination of benzylpenicillin by CE compared with HPLC results, confirmed good accuracy.

J Pharm Biomed Anal, 2004 Apr 16, 35(2), 243 - 58
Penicillin G acylase-based stationary phases: analytical applications; Calleri E et al.; A review of Penicillin G Acylase (PGA)-based stationary phases is given, focusing on immobilisation methods, selection of immobilisation material and applications in chiral liquid chromatography . Two immobilization methods, namely "in situ" and "in batch" techniques, are described for the immobilisation of PGA on silica supports . Microparticulate and monolithic silica, both functionalized with aminopropyl- and epoxy-groups, were used in the development of the PGA immobilised enzyme reactor (IMER) . The best results, in terms of PGA immobilised amount and enzyme activity, were obtained with the "in situ" immobilisation on epoxy monolithic silica . The use of PGA columns as enzyme reactors for the preparation of 6-APA and for the production of enantiomeric pure drugs in a one-step reaction in described . The review also covers the application of PGA-columns as chiral stationary phases for the separation of acidic enantiomers . An on-line chromatographic system based on the PGA-IMER combined with a switching valve to an analytical column is also described as a highly efficient tool to study the enantioselective hydrolyses properties of PGA . Finally a molecular modelling study is reported with the aim to give more insights into PGA-substrates interactions and to expand the application of these stationary phases as a chiral biocatalysts for pharmaceutical processes.

Clin Oral Investig, 2004 Sep, 8(3), 165 - 71 Epub 2004 Apr 02.
Effect of enamel matrix protein derivative on the attachment, proliferation, and viability of human SaOs(2) osteoblasts on titanium implants; Schwarz F et al.; The purpose of the present study was to investigate the effects of an enamel matrix protein derivative (EMD) on attachment, proliferation, and viability of human SaOs(2) osteoblasts on titanium implants . A total of 220 sand-blasted and acid-etched (SLA) titanium discs were placed into 24-well culture plates . Before cell inoculation, McCoy's 5A medium (MCM) containing EMD at 25 micro g/ml, 50 micro g/ml, 100 micro g/ml, and 200 micro g/ml was added, and the culture plates were incubated for 30 min . As control, MCM alone was used . Human osteoblast-like cells (SaOs(2)) (2 x 10(4) cells, fourth passage) were suspended in MCM containing 1% penicillin/streptomycin and 10% fetal bovine serum and then inoculated into the well chambers . The medium was changed after 3 days without the addition of EMD . At days 1, 3, and 6, DNA content of the cells was assessed using the CyQuant cell proliferation assay kit, and mitochondrial activity of the cells was measured using a CellTiter-Glo luminescent cell viability assay . The presence of EMD on the titanium discs at days 1 and 6 was evaluated using immunofluorescence stain (IFS) by means of polyclonal antibodies against amelogenin . Additionally, cell morphology was investigated using scanning electron microscopy . Enamel matrix derivative at 25 micro g/ml, 50 micro g/ml, 100 micro g/ml, and 200 micro g/ml demonstrated similar increases in cell proliferation as the control medium at days 3 and 6 ( P>0.05 between groups, respectively) . Proliferation, however, appeared to be ameliorated with increasing EMD concentrations . At 25 micro g/ml and 50 micro g/ml, EMD also demonstrated an increase in cell viability similar to the control medium at days 3 and 6 ( P>0.05 between groups, respectively), while EMD at 100 micro g/ml and 200 micro g/ml resulted in statistically significant higher increase in cell viability than in the control medium at day 6 ( P<0.001 between groups, respectively) . In all test groups, IFS at day 6 was markedly lower than at day 1 . Scanning electron microscopy revealed comparable cell morphology in all groups . Within the limits of the present study, it was concluded that EMD enhanced cell proliferation and viability of human SaOs(2) osteoblasts on SLA titanium implants in a concentration-dependent manner.

J Chromatogr A, 2004 Mar 26, 1031(1-2), 93 - 100
Evaluation of a monolithic epoxy silica support for penicillin G acylase immobilization; Calleri E et al.; In this work, a new type of penicillin G acylase (PGA)-based monolithic silica support was developed and evaluated for the chiral separation in HPLC . The preparation procedure consisted of two steps: preparation of an epoxy derivatized monolithic silica column and chemical modification of the epoxide groups with the enzyme chiral selector . The epoxy Silica-Rod column for the immobilization of PGA was prepared with the in situ modification process by using epoxy-silanes and the identification of the species bound to the surface was achieved by solid-state nuclear magnetic resonance . The enzyme was covalently immobilized to the surface of the derivatized monolithic column . The enantioselectivity and the performance of the developed column are discussed and compared to the corresponding experimental data obtained with a PGA-based microparticulate (5 microm) silica column.

Biotechnol Lett, 2004 Feb, 26(4), 343 - 50
Evaluation of magnetic polymer micro-beads as carriers of immobilised biocatalysts for selective and stereoselective transformations; Bozhinova D et al.; The kinetic, selective and stereoselective properties of enzyme immobilised on magnetic polymer beads with diameters in the range 1 microm was studied with penicillin amidase from E . coli . The enzyme was immobilised on epoxy and glutaraldehyde-activated poly(vinyl alcohol), poly(methylmetacrylate) and poly(vinyl acetate-divinylbenzene) magnetic beads . The amount of covalently bound active protein was dependent on the chemical modification of the matrix and increased at higher ionic strength of the immobilisation buffer . The small size of the magnetic beads, that reduces mass transfer limitations, and the decreased charge density in the electric double layer resulted in lower apparent Km values and higher efficiency for benzylpenicillin hydrolysis, higher stereoselectivity in condensation of R-phenylglycine amide with S- and R-Phe and in hydrolysis of racemic phenylacetyl-Phe and higher selectivity in kinetically controlled synthesis of cephalexin compared to the enzyme immobilised on larger and porous carriers.

Eur J Clin Pharmacol, 2004 May, 60(3), 211 - 6 Epub 2004 Mar 31.
Prescribing habits of general practitioners in the treatment of childhood respiratory-tract infections; Akici A et al.; OBJECTIVE: In the present study, prescribing behavior of general practitioners (GPs) was investigated in the example of childhood upper and lower respiratory-tract infections (URTIs and LRTIs) . STUDY DESIGN: A face-to-face interview was performed with 352 parents admitted to seven primary health care centers for their children diagnosed with URTI or LRTI . Prescriptions ( n=331) written by 25 GPs working at these centers were analyzed regarding legibility, format and suitability of drug choice . RESULTS: Almost 60% of parents had self-medicated their children prior to admitting to the doctor . Of the patients, 29 (8.2%) were not examined by the physicians, but were directly prescribed medicine . The physicians did not tell the diagnosis to 25.3% of the patients, did not inform 41.2% of them about the drugs and did not caution 95.7% about the side effects . Further, the physicians did not inform 42.6% of the patients about drug use instructions, did not inform 83.5% about the warnings and did not inform 81.2% about non-drug treatment . Approximately 5% of the individuals remembered the name of the drugs . Only 26.3% of the prescriptions were easily readable, and only five scripts (1.5%) contained all necessary information . The majority of the patients were given antibiotics, penicillin+beta lactamase inhibitors being the first . Paracetamol was the most frequently prescribed analgesic/antipyretic for both indications, followed by nimesulide and ibuprofen . CONCLUSIONS: The present study revealed inappropriate drug use in the treatment of respiratory-tract infections in children at the primary health care level in a district of Istanbul, Turkey . Furthermore, it has been shown that GPs practicing at primary health care centers should be trained to give adequate information about the disease and the treatment to the patients/parents to achieve good compliance and optimal drug therapy for children.

Clin Lab Haematol, 2004 Apr, 26(2), 153 - 6
Severe immune haemolysis after standard doses of Penicillin; Ho WK et al.; Summary Penicillin causes immune haemolytic anaemia by the 'drug-adsorption' mechanism and typically occurs after prolonged exposure to large doses of the drug . Withdrawal of the drug is associated with improved red cell survival and gradual cessation of haemolysis . Although this complication is uncommon, it can be potentially serious . An unusual case is described herein . The patient was exposed to a short course (9 days) of standard dose penicillin but suffered acute severe haemolysis about 1 week after cessation of therapy . A high titre anti-penicillin antibody (1 : 512) not cross-reacting with cephalosporins, was demonstrated . The delay in the development of immune haemolysis vis-a-vis penicillin therapy may be due to the patient being immunologically naive to the drug . Penicillin may persist for weeks in circulation, coating red cells and providing continued antigenic stimulation for the development of anti-penicillin antibody.

Bioorg Med Chem, 2004 Apr 15, 12(8), 1859 - 66
Bioactivation of carbamate-based 20(S)-camptothecin prodrugs; Pessah N et al.; Two new prodrugs of CPT were synthesized, based on carbamate linkages between the 20-hydroxy group of CPT and a linker designed to be enzymatically removed by either Penicillin-G-Amidase or catalytic antibody 38C2 . Cell growth inhibition assays showed an up-to-2250-fold difference in toxicity between the prodrugs and the active drug . A significant increase in toxicity was observed upon incubation of the enzyme or the catalytic antibody with the corresponding prodrug . The described derivatives of CPT further our knowledge in the design of prodrugs for use in selective approaches for targeted chemotherapy.

Ann Chir, 2004 Mar, 129(2), 96 - 9
{Pelvic actinomycosis revealed by pelvic peritonitis}; Michel P; Pelvic actinomycosis is an infection due to actinomyces organism associated with an intra-uterine contraceptive device . This infection is often revealed by an uni- or bilateral adrenal lesion . Lesions are sometimes more extensive and affect next pelvic organs: rectum, ureter, bladder . Diagnosis is often histologic with percutaneous biopsy or surgical biopsy (laparotomy or coelio surgery) . Treatment is mainly medical with prolonged use of penicillin (6 months in severely cases) . Surgery must be thrifty and conservative.

Wiad Lek, 2003, 56(9-10), 430 - 3
{Production of soluble intracellular adhesion molecule-1 (sICAM-1) in human endometrial cell culture}; Rzymski P et al.; Soluble ICAM-1 could play different roles in pathological mechanisms of human endometrium found in such diseases as endometriosis, spontaneous abortion and infertility . The aim of our study was to evaluate in vitro sICAM-1 secretion to medium dependent on menstrual cycle and estradiol (E2) stimulation . MATERIAL AND METHOD: Hysteroscopic biopsies in 19 infertile women . We established 16 cell cultures . Tissue was collected on DMEM, 5% FCS, 5% BSA with Penicillin, Streoptomycin, Gentamycin (2.5 mg/ml) . Isolation was performed during 4 hours . Tissue was washed twice, treated with collagenase 1A (1 mg/ml, 37 degrees C 2 hours), centrifuged 10 min by 1200 rpm . Cells were cultured in DMEM/5% FCS/5% BSA with Penicillin/Streptomycin . After 2 days of endometrial and stromal cells coculture D-Valine was used to stop fibroblasts' growth . Number of cells was calculated according to Buerker method . After 2 days estradiol in concentration of 10(-10 M) was added to some cultures . Soluble ICAM-1 concentrations in supernatants were evaluated using standard ELISA kit . T-Student test was used for statistical analysis, p value < 0.05 was considered significant . RESULTS: Median culture time was 14.9 (+/- 3.3) days . Longer cultures were obtained from women in follicular phase . The addition of estradiol prolonged culture by 3.8 days . The level of soluble ICAM-1 in supernatants in follicular phase was 17.6 ng/ml, in luteal 8.8 ng/ml . E2 influenced sICAM-1 production in culture (15.8 vs . 10.6 ng/ml) . CONCLUSIONS: Endometrial cells produce sICAM-1 constitutively . Soluble ICAM-1 concentrations are higher in follicular phase . Estradiol increases the excretion of sICAM-1.

Int J STD AIDS, 2004 Mar, 15(3), 183 - 8
A multi-district audit of the management of syphilis in genitourinary medicine clinics in Yorkshire; McClean H et al.; An audit against standards and guidelines of a representative sample of syphilis cases managed in genitourinary medicine clinics in Yorkshire was carried out . Satisfactory serological endpoints could be determined for about two-thirds of treated early and less than one-third of treated late syphilis cases . HIV antibody testing was obtained for less than half of all cases . Recently available national guidelines suggest inadequacy of both the dose and duration of treatments with procaine penicillin of asymptomatic late syphilis cases where lumbar puncture was not carried out . The diagnosis and management of syphilis is complex, and this audit demonstrates the importance of the systematic approach developed by genitourinary medicine clinic and laboratory services.

Am J Epidemiol, 2004 Apr 1, 159(7), 634 - 44
Potential impact of conjugate pneumococcal vaccines on pediatric pneumococcal diseases; O'Brien KL et al.; Children younger than age 2 years have the highest rates of invasive pneumococcal disease and play an important role in its transmission . In the United States, seven pneumococcal serotypes cause approximately 80% of invasive disease and represent approximately 60% of middle-ear isolates in children younger than age 2 years; the majority of penicillin-resistant strains are confined to these same few serogroups . Although unconjugated polysaccharide pneumococcal vaccines have demonstrated effectiveness in preventing invasive disease in adults, these vaccines fail to protect against otitis media or nasopharyngeal carriage and are poorly immunogenic in children younger than age 2 years . A new generation of pneumococcal vaccines has been developed, linking the capsular polysaccharide of seven to 11 serotypes to a protein carrier . The only pneumococcal vaccine approved to date for children younger than age 2 years is a seven-valent conjugate vaccine (PnCRM-7) (Prevnar; Wyeth Vaccines, Pearl River, New York), which contains serotypes 4, 6B, 9V, 14, 18C, 19F, and 23F . PnCRM-7 is more immunogenic than the polysaccharide pneumococcal vaccines and is 80-100% effective against vaccine-type invasive disease and 50-60% effective against vaccine-type pneumococcal otitis media . Routine immunization with pneumococcal conjugate vaccines should substantially reduce the morbidity, mortality, and costs associated with pneumococcal disease in children.

J Pharm Biomed Anal, 2004 Apr 1, 35(1), 65 - 73
Rapid estimation of kinetic parameters for thermal decomposition of penicillins by modulated thermogravimetric analysis; Miller JM et al.; Modulated thermogravimetic analysis (MTGA) is evaluated for the rapid estimation of thermal stability using several penicillin antibiotics as model compounds . The MTGA technique utilizes an oscillatory temperature program to obtain Arrhenius kinetic parameters through a mass loss during thermal degradation . To evaluate the reliability of this technique, activation energies (E(a)), log pre-exponential factor (logZ), and log first order rate constants (logk) obtained by MTGA for the thermal decomposition of ampicillin anhydrous, ampicillin trihydrate, ampicillin sodium salt, and penicillin G potassium salt are compared to existing literature values . The logk values estimated by MTGA agreed well with literature values when the weight loss observed by MTGA was shown to be due to the first decomposition step of the compound . The E(a) and logZ values determined by MTGA did not consistently agree with literature values as these parameters increased with decreasing heating rate (beta) . The increase in E(a) and logZ values with decreasing beta seemed to offset each other to some extent to yield a relatively consistent logk estimate regardless of beta.

Afr J Med Med Sci, 2003 Sep, 32(3), 321 - 2
Lactation failure in sows--case report; Ayoade GO; Cases of sixteen sows treated for lactation failure in piggery farms in Ibadan are reported . Fifteen of them had no complication of mastitis or mammary gland teat blockade . The fifteen uncomplicated cases responded favourably to the treatment with oxytocin (15-20 I . U . per sow) . Only two cases needed second treatment with oxytocin due to poor sustenance of flow from only one treatment . Milk flow was achieved in less than 5 minutes in all the treated sows after the intramuscular injection of the drug . The only sow with accompanying acute mastitis responded favourably to procaine penicillin injection . Early diagnosis and treatment of agalactia are important in the prevention and control of baby pig mortality . The favourable response of these sow lactation failures to treatment with oxytocin, confirms the hormonal imbalance as one of the major factors to be considered in the unknown aetiology of lactation failure or failure of milk ejection reflex.

Singapore Med J, 2004 Mar, 45(3), 105 - 9
Peritonsillar infections: local experience; Ong YK et al.; INTRODUCTION: The disease pattern and management of peritonsillar infections in Singapore General Hospital are studied . Other objectives are to determine if a seasonal variation exists and to examine the role of routine bacterial cultures and interval tonsillectomy . METHODS: This is a retrospective review of the management and outcome of patients with peritonsillar infections who were admitted acutely to Singapore General Hospital over a three-year period . RESULTS: Of 185 patients studied, 151 (81.6 percent) had peritonsillar abscess or quinsy and 34 (18.4 percent) had peritonsillar cellulitis . There were 139 males and 46 females, with a racial predisposition among Malays (p value is less than 0.0005) . There may be a seasonal variation with a bi-annual trend, though no correlation with upper respiration tract infections was noted . Treatment consisted mainly of incision and drainage (66 percent) or needle aspiration (34 percent) . No significant difference in the length of stay was noted in patients receiving penicillin alone, penicillin with metronidazole, or broad-spectrum antibiotics (p value is equal to 0.062) . Fourteen (7.6 percent) patients had recurrences, all of which occurred after the first month . Two patients (1 percent) had bilateral quinsy . CONCLUSION: Peritonsillar infections remain a common admitting diagnosis to the Otolaryngology department . A single episode of infection should no longer be an indication for tonsillectomy as the incidence of recurrence is low.

J Bacteriol, 2004 Apr, 186(7), 2215 - 20
The PaaX repressor, a link between penicillin G acylase and the phenylacetyl-coenzyme A catabolon of Escherichia coli W; Galan B et al.; The pac gene, encoding the penicillin G acylase from Escherichia coli W, is regulated by the PaaX repressor of the phenylacetate catabolic pathway . pac expression depends on the synthesis of phenylacetyl-coenzyme A . PaaX and the cyclic AMP receptor protein (CRP) bind in vitro to the Ppac promoter region . A palindromic sequence proposed as the PaaX operator is located upstream of the -35 box overlapping a CRP binding site, an unusual position that suggests a novel regulatory mechanism.

Ann Intern Med, 2004 Mar 16, 140(6), 409 - 18
Health plan members' views about disclosure of medical errors; Mazor KM et al.; BACKGROUND: Various authorities and national organizations encourage disclosing medical errors, but there is little information on how patients respond to disclosure . OBJECTIVE: To examine how the type of error, severity of adverse clinical outcome, and level of disclosure affect patients' responses to error and disclosure . DESIGN: Mail questionnaire survey (8 versions were developed) varying 3 factors in a completely crossed, randomized, factorial design . Each questionnaire included a vignette describing 1) a medical error (failure to check for penicillin allergy or inadequate monitoring of antiepileptic medication); 2) an associated clinical outcome (life-threatening or less serious); and 3) a physician-patient dialogue, with either full disclosure (acceptance of responsibility and an apology) or nondisclosure (expression of regret without acceptance of responsibility or an apology) . SETTING: New England-based health plan . PARTICIPANTS: Random sample of 1500 adult members received the questionnaire, with a 66% response rate . MEASUREMENTS: Likelihood of changing physicians, likelihood of seeking legal advice, ratings of patient satisfaction, trust and emotional reaction in response to a vignette and dialogue, and views on medical error and disclosure . RESULTS: Full disclosure reduced the reported likelihood of changing physicians and increased patient satisfaction, trust, and positive emotional response . Full disclosure reduced the reported likelihood of seeking legal advice in only 1 error-and-outcome vignette . In the other vignettes, the percentage of patients indicating that they would seek legal advice was relatively high even with full disclosure . Almost all respondents (98.8%) wanted to be told of errors, most (83%) favored financial compensation if harm occurred, and few (12.7%) favored compensation if no harm occurred . LIMITATIONS: Since the study was done in the context of a managed care plan in one geographic area, it could not assess whether the results are generalizable to other populations . In addition, it could not determine whether responses to the simulated situations used predict responses to real situations . CONCLUSIONS: Patients will probably respond more favorably to physicians who fully disclose medical errors than to physicians who are less forthright, but the specifics of the case and the severity of the clinical outcome also affect patients' responses . In some circumstances, the desire to seek legal advice may not diminish despite full disclosure.

Sheng Wu Yi Xue Gong Cheng Xue Za Zhi, 2004 Feb, 21(1), 1 - 7
{Alterations in expression of F-actin and DNA of fluid shear stress treated-mesenchymal stem cells affected by titanium particles loading}; Wu J et al.; Particulate wear debris within the bone-prosthesis microenvironment generated by normal wear and corrosion of orthopaedic implants is considered to be one of the main factors responsible for chronic aseptic inflammation and development of osteolysis in the long-term instability and failure of total joint arthroplasty . While the decrease in bone volume caused by wear debris-induced osteolysis could have been compensated by enough new bone matrix secreted by osteoblasts . Actually, the normal osteoblastic population depend on the regular differentiation and proliferation of their progenitor cells--bone marrow mesenchymal stem cells (MSCs) . This study aims to investigate the potential mechanism for the rat MSCs cytotoxicity upon exposure to Titanium (Ti) particles . Rat mesenchymal stem cells (rMSCs) isolated from 3-month-old male Sprague-Dawley rats by Percoll intensity gradient method were cultured in DMEM medium (low glucose) supplemented with 10% fetal bovine serum, 100 U/ml penicillin, and 100 micrograms/ml streptomycin in a humidified incubator with 5% CO2 at 37 degrees C . In order to gain the homogenous cell population, rMSCs were passaged to 3-4th subpassage which were used in all the experiment groups . Then rMSCs were seeded in the 6 well culture plates and exposed to three different circle diameters (mean size, TD1: 0.9 micron, TD2: 2.7 microns, TD3: 6.9 microns) with three different concentrations (0.1 wt%, 0.05 wt%, 0.01 wt%, W/V) at different durations (8 h, 16 h, 24 h,), respectively . Unexposed rMSCs were used as control . In the given periods of Ti loading, fluid shear stress (FSS) was applied to each group cells . The expression of F-actin and DNA of the rMSCs at the indicated time were determined with laser confocal scanning microscopy and image analysis software . The results showed that there was up-regulation expression of F-actin in the rMSCs without Ti particles loading but in the presence of FSS . Ti particles loading can suppress the expression of F-action and DNA of rMSCs, but this down-regulation response varied with the three circle diameter, concentrations and durations of Ti particles . Among three kinds of diametrically different Ti particles, submicron Ti particles (0.9 micron) had the greatest suppressive response on rMSCs, together with some apoptosis bodies . Under the same diameter condition, the inhibition induced by Ti particles loading was in a manner dependent on the particles concentration and exposure duration . The reductive effects produced from 0.1 wt% Ti was the greatest and earliest among the responses from Ti particles at three different concentrations; and the lower the concentration, the weaker the repressive influence . Furthermore, with the elongation of exposure to Ti particles, the expression of F-actin and DNA decreased gradually, the lowest level was at 32 h . These findings demonstrated that Ti particles loading can attenuate rMSCs' viability in a manner dependent on the circle diameter, particles concentration, treatment period, suggesting that a reduction in the number of viable MSCs together with a compromise of the their differentiation into functional osteoblast may exacerbate aseptic loosening of total joint implant . Further investigation into particles-mediated suppression of MCSs viability may reveal novel mechanism of implant loosening and aid in development and application of osteolytic drug therapy and the optimization of design and selection of future orthopaedic biomaterials, thereby improving long-term compatibility and stability for arthroplasty patients.

Theriogenology, 2004 Jun, 61(9), 1691 - 704
Influences of FSH and EGF on primordial follicles during in vitro culture of caprine ovarian cortical tissue; Silva JR et al.; Factors that control the onset of folliculogenesis are critical to female gamete production, but poorly understood . The aim of the present study was to investigate the effects of FSH and EGF on the activation and growth of goat primordial follicles in vitro . To this end, pieces of goat ovarian cortex were cultured in vitro for 1, 3 or 5 days, at 39 degrees C in an atmosphere containing 5% CO(2), in minimum essential medium supplemented with insulin, transferrin, selenium, pyruvate, glutamine, hypoxanthine, BSA, penicillin, streptomycin and fungizone and with or without FSH (100 ng/ml) and/or EGF (100 ng/ml) . At the end of the culture periods, the relative proportions of primordial, intermediate, primary and secondary follicles were calculated and compared with those in non-cultured tissue . In addition, mitotic activity of granulosa cells was studied by immunohistochemistry for proliferating cell nuclear antigen (PCNA) . In brief, it was found that goat primordial follicles activate spontaneously during culture in vitro and, while neither FSH nor EGF affected the proportion of primordial follicles that entered the growth phase, both stimulated an increase in oocyte and follicle diameter, especially in intermediate and primary follicles cultured for 5 days . On the other hand, there was no significant effect of culture or either growth factor on the proportion of PCNA-stained growing follicles . Contrary to expectations, neither FSH nor EGF affected follicle viability or integrity during culture, since the percentages of intact follicles did not differ between control, FSH and/or EGF containing medium . In conclusion, this study demonstrated that goat primordial follicles activate spontaneously in vitro, and that both FSH and EGF stimulate an increase in follicle size by promoting oocyte growth.

Int J Pharm, 2004 Apr 1, 273(1-2), 149 - 58
Influence of magnesium glutamate on stability of penicillin G aqueous solution; Michnik A et al.; Differential scanning microcalorimetry (DSC) has been used to determine the influence of magnesium glutamate on the stability of penicillin G in aqueous solution . The degradation of penicillin is accompanied by an evolution of heat and has been observed as an irreversible, scan rate dependent, broad exothermic transition . The increase of the transition temperature Tm and enthalpy change DeltaH with increasing magnesium glutamate concentration indicates the increase of penicillin G stability . The kinetic parameters describing the penicillin decomposition process, obtained for a reaction following a first-order course, suggest maximum penicillin G stability if about two molecules of salt per one penicillin molecule are present in solution.

Clin Microbiol Infect, 2004 Mar, 10(3), 229 - 33
Prognostic factors affecting deaths from adult tetanus; Saltoglu N et al.; The objective of this study was to determine prognostic factors related to death from adult tetanus . Fifty-three cases of tetanus, 25 females and 28 males, were treated in Cukurova University Hospital during 1994-2000 . The mean age was 46.6 years . Forty-one (77.7%) patients came from rural areas . Most (64.1%) cases had minor trauma, but 19 (35.8%) had deep injuries . The mean incubation period was 11.5 days . Mortality was high (52.8%), caused by cardiac or respiratory failure or complications, and was related to the length of the incubation period . In cases with an incubation period < or = 7 days, the mortality rate was 75% (p 0.07) . Mortality was significantly associated with generalised tetanus (p < 0.05), fever of > or = 40 degrees C, tachycardia of > 120 beats/min (p < 0.05), post-operative tetanus (p 0.03), and the absence of post-traumatic tetanus vaccination (p 0.068) . Patients who were given tetanus human immunoglobulin or tetanus antiserum (p > 0.05) had similar outcomes . Patients who were given penicillin had a mortality rate similar to patients who were given metronidazole (p 0.15) . The mortality rate was higher (92%) in patients with severe tetanus than in patients with moderate disease (53%) . By multivariate analysis, the time to mortality caused by tetanus, and also the mortality rate, were both related significantly to age and tachycardia.

Ann Trop Paediatr, 2004 Mar, 24(1), 33 - 40
Invasive pneumococcal disease in Jamaican children; McGregor D et al.; A 5-year retrospective review of cases of invasive pneumococcal disease admitted to the Bustamante Hospital for Children, Jamaica was conducted . A total of 111 cases were identified . The estimated incidence of invasive pneumococcal disease in Kingston and St Andrew was 21/100,000 children under the age of 10 years . The majority of cases (76%) were in the under-2-years age group . All four deaths were of infants . Pre-existing medical conditions included sickle cell disease, HIV and undernutrition . The rate of resistance to penicillin was 13.8% . Meningitis accounted for three of the four deaths identified and poor outcome was identified in 28% of cases of meningitis . We conclude that invasive pneumococcal disease causes significant morbidity and mortality in young Jamaican children . Strategies directed at preventing HIV infection and malnutrition and improving the care of children with sickle cell disease and HIV infection would significantly reduce disease incidence.

Ann Trop Med Parasitol, 2004 Jan, 98(1), 59 - 63
Benzathine penicillin, metronidazole and benzyl penicillin in the treatment of tetanus: a randomized, controlled trial; Ganesh Kumar AV et al.; Penicillin, the drug of choice in tetanus, may potentiate the effect of tetanus toxin by inhibiting the type-A (GABAA) receptor for gamma-amino-n-butyric acid . Metronidazole has therefore been suggested as an alternative . Intramuscular benzathine penicillin (1.2 million units as a single dose; N=56), enteral metronidazole (600 mg every 6 h for 10 days; N=55) and intravenous benzyl penicillin (2 million units every 4 h for 10 days; N=50) were therefore compared, in a randomized, controlled trial, among patients with all grades of tetanus . On presentation, the three treatment groups were similar in terms of age and sex distributions, immune statuses, durations of illness, and their APACHE-II scores and Ablett's grades of tetanus . Of the patients given benzathine penicillin, 36 required tracheostomy, 10 neuromuscular blockade, and 23 mechanical ventilation; the corresponding numbers for the metronidazole (34, 12 and 18, respectively) and benzyl-penicillin groups (39, 12 and 25, respectively) were similar (P>0.10) . The incidences of dysautonomia and nosocomial pneumonia and the numbers of in-hospital deaths (26 with benzathine penicillin, 19 with metronidazole and 22 with benzyl penicillin; P=0.392) were also similar in each treatment arm . The length of the hospital stay was longer in the patients receiving benzyl penicillin than in the benzathine-penicillin or metronidazole groups, with means (S.D.) of 21.9 (15), 16.9 (11) and 19.9 (15) days, respectively, but the difference was not statistically significant (P=0.09) . Although the three antibiotic regimens investigated appear equally effective, benzathine penicillin offers the convenience of a single, intramuscular injection instead of the 10 days of therapy needed with the other two drugs.

Biotechnol Lett, 2004 Jan, 26(2), 97 - 101
Production of 6-aminopenicillanic acid in aqueous two-phase systems by recombinant Escherichia coli with intracellular penicillin acylase; Cao XJ et al.; Bioconversion of penicillin G in PEG 20000/dextran T 70 aqueous two-phase systems was achieved using the recombinant Escherichia coli A56 (ppA22) with an intracellular penicillin acylase as catalyst . The best conversion conditions were attained for: 7% (w/v) substrate (penicillin G), enzyme activity in bottom phase 52 U ml(-1), pH 7.8, temperature 37 degrees C, reaction time 40 min . Five repeated batches could be performed in these conditions . Conversions ratios between 0.9-0.99 mol of 6-aminopenicillanic acid (6-APA) per mol of penicillin G, were obtained and volumetric productivity was 3.6-4.6 micromol min(-1) ml(-1) . In addition the product 6-APA could be directly crystallized from the top phase with a purity of 96%.

Dermatol Online J . 2003 Dec;9(5):17.
An interesting case of primary cutaneous actinomycosis; Roy D et al.; Actinomycosis is an infection commonly seen in tropical countries . It is characterized by chronic and progressive suppurative inflammation, typically presenting on the neck, thorax, and abdomen . Primary cutaneous actinomycosis is a rare entity, and the diagnosis requires a high index of clinical suspicion . Anaerobic cultures may be negative despite repeated attempts . Microscopic examination reveals the diagnosis in the majority of cases, and treatment requires administration of parenteral or oral penicillin for at least 6 weeks . We report a case of cutaneous actinomycosis affecting the arm . This patient was treated with phenoxymethylpenicillin.

Anal Chem, 2004 Mar 1, 76(5), 1518 - 23
Metabolite-sensitive holographic biosensors; Marshall AJ et al.; A new type of biosensor that combines the inexpensiveness and mass-produceability of reflection holograms with the selectivity and specificity of enzymes is described . pH-sensitive holographic sensors were fabricated from ionizable monomers incorporated into thin, polymeric, hydrogel films which were transformed into volume holograms using a diffusion method coupled with holographic recording, using a frequency-doubled Nd:YAG laser (532 nm) . These holograms were used as transducer systems to monitor the pH changes associated with specific enzymatic reactions to construct prototype urea- and penicillin-sensitive biosensors . The diffraction wavelength (color) of the holographic biosensors was used to characterize their shrinkage and swelling behavior as a function of analyte concentration . The potential of these sensors for the measurement of the clinically and industrially important metabolites urea and penicillin G is demonstrated.

Org Biomol Chem, 2004 Mar 7, 2(5), 716 - 24 Epub 2004 Feb 03.
Preparation of beta- and gamma-lactams from carbamoyl radicals derived from oxime oxalate amides; Scanlan EM et al.; A general synthetic route to oxime oxalate amides was developed and applied to the preparation of molecules incorporating N-benzyl-N-alkenyl amides linked with acetone oxime or benzaldoxime units . In addition, 2-substituted-thiazolidine-4-carboxylic acid methyl ester amides of oxalyl benzaldoxime were also prepared . It was shown by EPR spectroscopy that the oxalyl benzaldoxime amides dissociated to produce benziminyl and carbamoyl (aminoacyl) radicals when photolysed with 4-methoxyacetophenone as a photosensitizer . Carbamoyl radicals derived from N-alk-3-enyl oxime oxalate amides underwent ring closure to afford pyrrolidin-2-ones . The analogous N-alk-2-enyl precursors afforded azetidin-2-ones . Reactions of the cyclohexenyl and cinnamyl oxime oxalate amides afforded a bicyclic beta-lactam and a 3-benzyl-substituted beta-lactam respectively . Interestingly, both products were isolated as hydroxylated compounds . A thiazolidine-derived oxime oxalate amide containing an isobutenyl side chain also dissociated with production of the corresponding thiazolidinyl-carbamoyl radical, as shown by EPR spectroscopy . GC-MS evidence indicated that this radical cyclised to afford some of the corresponding penicillin derivative

Eur J Cancer Care (Engl), 2003 Dec, 12(4), 369 - 71
Documented allergies of patients with cancer; Chernecky C; The purpose of this study was to determine and quantify the types of allergies that occur in patients with cancer . The study sample consisted of computer-generated pharmacy records of 4510 inpatients from two oncology inpatient units over a 1-year period from a large urban hospital in the USA . Compliance with computer entry was monitored in order to ensure data accuracy . Results of the study indicate that the percentages of stated allergies for persons with cancer might be higher than those for overall populations . The top four medication allergies were penicillin, sulpha, codeine and contrast media . The top four food allergies were milk, eggs, chocolate and strawberries and the top four environmental allergies were bee stings, chemical sprays, dust and mould.

Bioorg Med Chem Lett, 2004 Mar 8, 14(5), 1299 - 304
Penicillin-derived inhibitors that simultaneously target both metallo- and serine-beta-lactamases; Buynak JD et al.; The synthesis and beta-lactamase inhibitory activity of four 6-(mercaptomethyl)penicillinates and the four corresponding 6-(hydroxymethyl)penicillinates are described . These penicillins include both C6 stereoisomers as well as the sulfide and sulfone oxidation states of the penam thiazolidine sulfur . All compounds were evaluated as inhibitors of representative metallo- and serine-beta-lactamases enzymes . Selected (mercaptomethyl)penicillinates are shown to inactivate both metallo- and serine-beta-lactamases and to display synergism with piperacillin against beta-lactamase producing strains.

J Laryngol Otol, 2004 Feb, 118(2), 143 - 5
Sudden sensorineural hearing loss following intramuscular administration of penicillin; Escada PA et al.; We report a case of sudden hearing loss in a patient with acute exudative tonsillitis, occurring 15 minutes after the intramuscular administration of penicillin . Audiological evaluation documented a profound sensorineural hearing loss of the cochlear type . The mechanism of the hearing loss was probably an immediate hypersensitivity (type I) allergic drug reaction . Penicillin is used frequently for the treatment of several infections . Allergic reactions to penicillin are well known and include urticaria, maculopapular exanthems, angio-oedema, bronchospasm and anaphylaxis, but sudden hearing loss has never been recorded.

Saudi Med J, 2004 Feb, 25(2), 229 - 33
Primary actinomycosis of the abdominal wall; Khalid K et al.; Primary actinomycosis of the abdominal wall is a rare clinical entity . Only 7 adequately described cases have been reported in the English literature . We report a case of isolated abdominal wall actinomycosis involving the left lower quadrant of the abdominal wall in a 32-year-old diabetic male . The diagnosis was confirmed by histopathological examination . Surgical drainage of the abscess followed by long-term administration of penicillin resulted in cure . The clinicopathological spectrum of actinomycosis is reviewed and isolated involvement of the abdominal wall is characterized in light of the knowledge acquired from the available literature on this rare clinical presentation . The significance of obtaining tissues for culture and histopathology in all inflammatory lesions is emphasized.

Saudi Med J, 2004 Feb, 25(2), 156 - 63
Cytotoxic effects of some animal and vegetable extracts and some chemicals on liver and colon carcinoma and myosarcoma; Bayazit V; OBJECTIVE: To study, the cytotoxic effects of some biological and chemical agents on G1, S, G2, M and G0 phases of liver and colon carcinomas and myosarcoma cells obtained with chemical carcinogens dimethylbenzanthracene (DMBA) and cadmium chloride . METHODS: Eight rabbit livers, colon carcinoma and myosarcoma cell lines were obtained by injection of DMBA in the Biology Laboratory, of the University of Dumlupinar, Kutahya, Turkey between January 2001 and June 2003 . All lines were grown at 37 degrees celsius and 5% carbon dioxide in sterile RPMI-1640 medium with 10% fetal bovine serum after addition of glutamate, penicillin (50 units/ml) and streptomycin (50 ug/ml) (complete medium) . Cells were grown on standard tissue culture plastic flasks to 80% confluence and passed by trypsinization . RESULTS: Tortoise (Testudo graeca) shell, sponge (Geodia cydonium), medusa (Aurelia aurita), meat flies (Calliphora erythrocephala) larva, frog (Rana ridibunda) larva and juniper (Juniperus communis) berry extracts killed a large amount of the liver and colon carcinomas and the myosarcoma cells in G2, M and G0 phases (p<0.01) . The mistletoe (Viscum album) extract had more effect in only the G0 phase (p<0.05) . Genistein, genistin, glycitein, glycitin, daitzein and daitzin have significantly decreased in the cancer cells tests, particularly, genistein and daitzein caused the apoptotic effect in G2, M and G0 phases (p<0.01) . Cesium chloride, a mixture of cesium chloride with magnesium chloride had the most effect on tumor cells (p<0.01) . AzhexSi, Azhex-AzhepSi, Et-Azhex-AzhepSi, AzhepSi, Hexamine and DL 54 have been inhibited in various levels of the cancer cells (p<0.05, p<0.01) . CONCLUSION: This data suggest that some biological extracts and chemicals tested may be useful chemotherapeutic agents to inhibit the growth of cancer cells . This study sheds some light for new anti cancerogenic experiments preventing various cancers on humans.

Childs Nerv Syst, 2004 Mar, 20(3), 176 - 82 Epub 2004 Feb 10.
The effect of experimental epilepsy induced by penicillin administration during pregnancy on nestin expression in the immature rat cerebellum . A light, electron microscopic, and immunohistochemical study; Uyanikgil Y et al.; INTRODUCTION: Recent knowledge regarding the effect of epileptic seizures in pregnant women on newborns was limited and, therefore, it was difficult to suggest the proper clinical guidelines and to take precautions against it . Studies evaluating the morphological effects of epileptic seizure during pregnancy on newborns in various experimental models are valuable . Therefore, the current study was designed to investigate the morphological changes in the cerebellum of newborn pups of rats subjected to experimental epilepsy during pregnancy . MATERIALS AND METHODS: Swiss Albino rats were divided into three groups (six animals in each) . In the first group (experimental group) an acute grand mal epileptic seizure was induced by 400 IU penicillin-G administration into their intrahippocampal CA3 region with a stereotaxic device during the 13th day of their pregnancy . The second group (intrahippocampal saline-injected sham group) and the third group (untreated animals) were the control groups . On the 1st neonatal day, pups were perfused with intracardiac fixative solution under anesthesia, and newborn cerebellums were dissected surgically for light and electron microscopic studies . RESULTS: In an immunohistochemical study using Rat-401 monoclonal antibody and peroxidase, the intermediate filament nestin was detected in the developing cerebellar tissue . Histologically, normal migration and cerebellar maturation were determined in the newborn rat cerebellum in the control and sham-operated groups . It was observed that the morphological structure of the cerebellar cortex in the experimental group was compromised in the early embryonal period . In contrast to the control and sham groups, it was found that nestin (+) cell density was increased in the experimental epilepsy group . CONCLUSIONS: It has been concluded that epileptic convulsions during embryonic life may cause early neurogenesis and delayed maturation, which explains the harmful effects of epileptic grand mal seizures, hypoxia, and obstetric trauma to the embryo at the early stage of neuronal differentiation . However, further studies are necessary to investigate epileptic pregnant phenomena and to characterize the possible relationship between epilepsy and congenital malformations as well as mental retardation.

Anal Biochem, 2004 Mar 1, 326(1), 1 - 12
Comparison of high-performance liquid chromatography and fluorophore-assisted carbohydrate electrophoresis methods for analyzing peptidoglycan composition of Escherichia coli; Li SY et al.; Currently, reversed-phase high-performance liquid chromatography (HPLC) is the method of choice for determining the types and amounts of muropeptide subunits comprising bacterial peptidoglycan . Although effective and sensitive, the technique does not lend itself to high throughput screening, and its complexity and equipment requirements may dissuade some investigators from pursuing certain types of cell wall experiments . Previously, we showed that muropeptides can be labeled with a fluorescent dye and separated by fluorophore-assisted carbohydrate electrophoresis (FACE), a simple and rapid gel procedure that might serve as a prelude to more intense analysis by HPLC . To validate the utility of FACE, we used both techniques to perform a side-by-side analysis of the peptidoglycan of eight mutants and their Escherichia coli parent strain . FACE and HPLC both detected the seven major muropeptides, which represent more than 95% of the total muropeptides present in this organism . In addition, FACE returned the same relative and quantitative results in 92% of 72 measurements, indicating that the procedure gives an accurate overview of peptidoglycan composition . The results also suggest a possible biochemical activity for the AmpC and AmpH proteins of E . coli, and the use of FACE as an in vitro enzyme assay detected possible substrate preferences for the endopeptidase penicillin binding protein 4.

Jpn J Ophthalmol, 2004 Jan-Feb, 48(1), 65 - 7
Retinal vasculitis due to secondary syphilis; Yokoi M et al.; BACKGROUND: Retinal vasculitis is one of the manifestations of ocular syphilis . CASE: A 29-year-old man was referred to our hospital with the complaint of sudden visual loss in the left eye lasting more than three weeks . OBSERVATIONS: Ophthalmoscopic examination showed retinal hemorrhages, edema, and sheathing of large retinal arteries and veins . Fluorescein angiography revealed extensive occlusion of the affected retinal arteries, veins, and capillaries . Little evidence of uveitis or vitritis was observed . The fluorescent treponemal antibody-absorption test was positive, and the Treponema pallidum hemagglutination titer was 1:10,240 . The treatment with penicillin was effective, leading to resolution of the retinal hemorrhages and edema, although occlusion of the retinal vessels persisted . CONCLUSIONS: Vascular occlusion occurred simultaneously in large retinal arteries, arterioles, and capillaries as well as in segments of retinal veins, resulting in irreversible changes in the vascular walls.

Appl Environ Microbiol, 2004 Feb, 70(2), 1249 - 51
Stabilization of penicillin G acylase from Escherichia coli: site-directed mutagenesis of the protein surface to increase multipoint covalent attachment; Abian O et al.; Three mutations on the penicillin acylase surface (increasing the number of Lys in a defined area) were performed . They did not alter the enzyme's stability and kinetic properties; however, after immobilization on glyoxyl-agarose, the mutant enzyme showed improved stability under all tested conditions (e.g., pH 2.5 at 4 degrees C, pH 5 at 60 degrees C, pH 7 at 55 degrees C, or 60% dimethylformamide), with stabilization factors ranging from 4 to 11 compared with the native enzyme immobilized on glyoxyl-agarose.

Appl Environ Microbiol, 2004 Feb, 70(2), 1031 - 9
Inactivation of the lys7 gene, encoding saccharopine reductase in Penicillium chrysogenum, leads to accumulation of the secondary metabolite precursors piperideine-6-carboxylic acid and pipecolic acid from alpha-aminoadipic acid; Naranjo L et al.; Pipecolic acid serves as a precursor of the biosynthesis of the alkaloids slaframine and swainsonine (an antitumor agent) in some fungi . It is not known whether other fungi are able to synthesize pipecolic acid . Penicillium chrysogenum has a very active alpha-aminoadipic acid pathway that is used for the synthesis of this precursor of penicillin . The lys7 gene, encoding saccharopine reductase in P . chrysogenum, was target inactivated by the double-recombination method . Analysis of a disrupted strain (named P . chrysogenum SR1-) showed the presence of a mutant lys7 gene lacking about 1,000 bp in the 3'-end region . P . chrysogenum SR1- lacked saccharopine reductase activity, which was recovered after transformation of this mutant with the intact lys7 gene in an autonomously replicating plasmid . P . chrysogenum SR1- was a lysine auxotroph and accumulated piperideine-6-carboxylic acid . When mutant P . chrysogenum SR1- was grown with L-lysine as the sole nitrogen source and supplemented with DL-alpha-aminoadipic acid, a high level of pipecolic acid accumulated intracellularly . A comparison of strain SR1- with a lys2-defective mutant provided evidence showing that P . chrysogenum synthesizes pipecolic acid from alpha-aminoadipic acid and not from L-lysine catabolism.

Biotechnol Prog, 2004 Jan-Feb, 20(1), 117 - 21
Thermodynamically controlled synthesis of amide bonds catalyzed by highly organic solvent-resistant penicillin acylase derivatives; Abian O et al.; A study of various direct condensations between different amines, having very high pK values, and unmodified acyl donors has been performed . This has been possible by the use of a very stable PGA derivative . First, it has been found that the higher the cosolvent concentration, the higher the pK of the acyl donor and thus the higher the yield . Therefore, these high concentrations of cosolvents seem to be a requisite for certain enzymatic condensations . Using ethanolamine and 2-hydroxy-2-phenylethyl-amine as nucleophiles and phenyl acetic acid as the acyl donor, the increase in the diglyme concentration from 50 to 90% (v/v) permitted improvement of not only the yield (reaching values higher than 99% in both cases) but also the reaction rates (by 360- or 3-fold, respectively) . However, even when using PGA preparations stabilized by multipoint covalent attachment, it was not possible to obtain these results by inactivation of the enzyme derivative . Thus, in the protection of the octylamine with phenylacetic acid in 90% diglyme, the enzymatic activity was more than 20-fold higher using the hydrophilized derivative than the glyoxyl PGA, which allowed us to obtain a yield higher than 99% . Thus, the use of hydrophilized derivatives that are very stable even in the presence of high concentrations of organic solvents opens new opportunities in the use of PGA in organic chemistry.

Toxicol Appl Pharmacol, 2004 Feb 1, 194(3), 257 - 69
Molecular multiple endpoint embryonic stem cell test--a possible approach to test for the teratogenic potential of compounds; zur Nieden NI et al.; The embryonic stem cell test (EST) examines the cytotoxicity of chemical compounds on embryonic stem (ES) cells and 3T3.A31 fibroblasts . Additionally, the EST measures the ability of ES cells to differentiate into contracting cardiomyocytes following drug exposure . In this study, we introduce new endpoints to obtain a molecular multiple endpoint EST (mme-EST), enabling the identification of potential chemical effects on osteogenic, chondrogenic and neural differentiation in addition to the traditional endpoint of cardiomyocyte differentiation . Six compounds in three classes with known teratogenic in vivo potential were assayed with the mme-EST in a pilot study: penicillin G (non-teratogenic), 5-fluorouracil and retinoic acid (strongly teratogenic), diphenylhydantoin, valproic acid and thalidomide (moderately teratogenic) . While the traditional EST measures a morphological endpoint, we included molecular markers of differentiation as endpoints . With the mme-EST, every compound could be classified correctly according to its known teratogenic potential in vivo . Penicillin G, 5-fluorouracil and diphenylhydantoin inhibited differentiation of all endpoints equally . Interestingly, valproic acid showed the strongest inhibition of neural differentiation, while thalidomide specifically inhibited osteogenic development . Retinoic acid, on the other hand, supported neural but inhibited chondrogenic and osteogenic differentiation concentration-dependently . Valproic acid and thalidomide, classified incorrectly with the established EST model, were classified correctly with the mme-EST according to their effects on specific endpoints . This pilot study indicates that the predictive value of the EST may be enhanced by including further differentiation endpoints.

Zhonghua Er Ke Za Zhi, 2003 Jan, 41(1), 29 - 30
{Clinical manifestations of 30 cases with Lyme disease}; Qi X; OBJECTIVE: To understand the clinical characteristics of Lyme disease in children . METHODS: Case records of 30 children with Lyme disease who were admitted to the pediatric department of Forest Hospital, Inner Mongolia from May 1995 to Oct . 2000, were reviewed . Twenty-one cases were male and 9 were female . Their age ranged from 2 to 14 years . The possible factors associated with the onset, incubation period, clinical manifestations of the organ systems and response to treatment were analyzed . RESULTS: Each of the 30 cases had a history of tick bite for one time or more . The incubation period was 1 to 14 days . All of them were hospitalized for typical erythema migrans . Among the 30 cases, 21 (70%) showed symptoms of acute upper respiratory tract infection; 4 (13%) showed circulatory system symptom and manifestations of myocardial lesion; 3 (10%) had joint pain; 1 case (3%) had eye symptom and another case (3%) had nervous system symptoms, such as headache, vomiting, drowsiness, neck stiffness and so on . EEG and spinal fluid test showed some abnormal results . All the 30 cases were positive for IgG antibody to Lyme spirochetes with titers higher than 1:128 . Penicillin or cefazolin was effective in treatment of the patients . CONCLUSION: The incubation period of the disease observed among this series of patients was 1-14 d . Lyme disease in this group of patients involved multiple organ systems while erythema migrans and arthralgia were the most frequently seen manifestations . Most of the patients had a favorable outcome with no sequelae.

Biotechnol Bioeng, 2004 Mar 5, 85(5), 553 - 60
Combinatorial formulation of biocatalyst preparations for increased activity in organic solvents: salt activation of penicillin amidase; Lindsay JP et al.; A combinatorial experimental technique was used to identify salts and salt mixtures capable of activating penicillin amidase in organic solvents for the transesterification of phenoxyacetate methyl ester with 1-propanol . Penicillin amidase was lyophilized in the presence of various chloride and acetate salts within 96-deep-well plates and catalytic rates measured to determine lead candidates for highly salt-activated preparations . The kinetics of the most active formulations were then further evaluated . These studies revealed that a formulation consisting of 98% (w/w) of a 1:1 KAc:CsCl salt mixture, 1% (w/w) enzyme, and 1% (w/w) potassium phosphate buffer was approximately 35,000-fold more active than the salt-free formulation in hexane, as reflected in values of V(max)/K(m) . This extraordinary activation could be extended to more polar solvents, including tert-amyl alcohol, and to formulations with lower total salt contents . A correlation was found between the kosmotropic/chaotropic behavior of the salts (as measured by the Jones-Dole B coefficients) and the observed activation . Strongly chaotropic cations combined with strongly kosmotropic anions yielded the greatest activation, and this is likely due to the influence of the ions on protein-water and protein-salt interactions .

Prog Neuropsychopharmacol Biol Psychiatry, 2004 Mar, 28(2), 417 - 20
A case of neurosyphilis showing a marked improvement of clinical symptoms and cerebral blood flow on single photon emission computed tomography with quantitative penicillin treatment; Ide M et al.; A 31-year-old woman manifested significant emotional symptoms and personality change due to neurosyphilis; her clinical symptoms were improved with quantitative penicillin treatment . On admission, magnetic resonance imaging (MRI) showed no abnormal findings, while N-isopropyl-p-{123I} iodoamphetamine single photon emission computed tomography (123I-IMP SPECT) initially showed a remarkable increase in cerebral blood flow (CBF) in the cerebral cortex . This increase disappeared after improvement of the patient's clinical symptoms with treatment . It appears that the increase in CBF might have reflected an active inflammatory state of neurosyphilis and that its disappearance might therefore represent successful treatment with penicillin for neurosyphilis . Our case study suggests that single photon emission computed tomography (SPECT) is a useful method for evaluating an inflammatory state and for assessing the effect of therapy on neurosyphilis.

Mikrobiyol Bul, 2003 Oct, 37(4), 297 - 9
{A case of acute pancreatitis due to Weil's disease}; Karaahmetoglu S et al.; Leptospirosis, the most common vasculitic zoonosis in the world, is characterized with jaundice and acute renal failure . However, pancreatitis is an uncommon complication of leptospirosis . In this report, an acute pancreatitis case due to Weil's disease has been presented . A 31-year-old female patient with high levels of glucose, blood urea nitrogen, creatinine, creatine kinase, bilirubin, amylase and lipase, has been diagnosed to have leptospirosis by the high positive result (1/800) of microscopic agglutination test against Leptospira interrogans serogroup icterohemorrhagiae . The patient has been treated with supportive and symptomatic therapy, and with penicillin G for leptospirosis . Following triple hemodialysis, all the blood biochemistry tests returned to normal on the tenth day of therapy . This case was reported to draw attention to Leptospira infections which should be considered in the differential diagnosis of patients with jaundice and pancreatitis.

J Biol Chem, 2004 Apr 9, 279(15), 14917 - 21 Epub 2004 Jan 27.
A novel beta-lactamase activity from a penicillin-binding protein of Treponema pallidum and why syphilis is still treatable with penicillin; Cha JY et al.; Treponema pallidum, the causative agent of syphilis, is sensitive to penicillins . Yet, an abundant membrane-bound protein of this organism, Tp47, turns over penicillins . It is shown herein that the turnover process is a hydrolytic reaction that results in the corresponding penicilloates, products that have their beta-lactam bonds hydrolyzed . This is the reaction of beta-lactamases, bona fide resistance enzymes to beta-lactam antibiotics . Remarkably, the x-ray structure of Tp47 bears no resemblance to any other beta-lactamases or the related penicillin-binding proteins . Furthermore, evidence is presented that the reaction of Tp47 takes place in the absence of the zinc ion and does not involve intermediary acyl enzyme species . Hence, the beta-lactamase activity of Tp47 is the fifth known mechanism for turnover of beta-lactam antibiotics . Tp47 also exhibits a penicillin binding reaction, in the process of which the enzyme is covalently modified in the active site . The two reactions take place in two different active sites, and the events of the beta-lactamase activity are over 2,000-fold more rapid than the penicillin binding reaction . The level of beta-lactamase activity is high and is held back only by a strong product-inhibition component to the catalytic process . If natural selection would result in a mutant variant of Tp47 that overcomes product inhibition for the beta-lactamase activity, a novel bona fide resistance to penicillins will emerge in Treponema, which will be a disconcerting clinical development . The physiological functions of Tp47 are not known, but it is likely that this is at least a bifunctional enzyme involved in the processing of the Treponema peptidoglycan as a substrate.

Sex Transm Dis, 2004 Feb, 31(2), 127 - 32
Congenital syphilis in Russia: the value of counting epidemiologic cases and clinical cases; Salakhov E et al.; BACKGROUND: Congenital syphilis (CS) reports in Russia increased 26-fold from 1991 to 1999 . Case reports included only infants who were clinical cases, had persistent serologic changes, or confirmed syphilitic stillbirth . Although not reported, policies stipulate that infants of inadequately treated or untreated mothers receive preventive penicillin treatment . GOAL: We examined whether risk factors and consequences for epidemiologic cases of CS (infants of inadequately treated mothers) resembled those of clinical cases and differed from those of noncases (infants of adequately treated mothers) . STUDY DESIGN: A retrospective record review from Maternity Houses in 5 sites identified 715 syphilis-infected women who gave birth . RESULTS: Among women with maternal syphilis, 11% (n = 81) of infants were clinical cases, 56% (n = 402) were epidemiologic cases, and 33% (n = 232) were noncases of CS . Compared with noncases, maternal risk factors for epidemiologic cases included nonresidence (P <0.01), late syphilis (P <0.01), unemployment (P <0.01), no prenatal care (P <0.01), and syphilis testing at >/=28 weeks (P <0.01) . Each of these was also significant for being a clinical case . Associated consequences of CS for the epidemiologic cases included increases in stillbirth (P <0.01), preterm birth (P <0.01), low birth weight (P <0.01), transfer to a pediatric hospital (P <0.01), and abandonment (P <0.05) . Each of these except stillbirth was significantly elevated among clinical cases . Nearly half of the epidemiologic cases had no record of any penicillin treatment for the infant . Epidemiologic cases were significantly more likely than noncases to have no clinical or laboratory follow up . CONCLUSION: In Russia, maternal risk factors and perinatal consequences for epidemiologic cases of CS resembled those of clinical cases . Expanding national reporting to include epidemiologic cases would strengthen CS prevention and monitoring.

J Biotechnol, 2004 Feb 19, 108(1), 61 - 77
Intelligent real-time performance monitoring and quality prediction for batch/fed-batch cultivations; Undey C et al.; Supervision of batch bioprocess operations in real-time during the progress of a batch run offers many advantages over end-of-batch quality control . Multivariate statistical techniques such as multiway partial least squares (MPLS) provide an efficient modeling and supervision framework . A new type of MPLS modeling technique that is especially suitable for online real-time process monitoring and the multivariate monitoring charts are presented . This online process monitoring technique is also extended to include predictions of end-of-batch quality measurements during the progress of a batch run . Process monitoring, quality estimation and fault diagnosis activities are automated and supervised by embedding them into a real-time knowledge-based system (RTKBS) . Interpretation of multivariate charts is also automated through a generic rule-base for efficient alarm handling . The integrated RTKBS and the implementation of MPLS-based process monitoring and quality control are illustrated using a fed-batch penicillin production benchmark process simulator.

Dtsch Med Wochenschr, 2004 Jan 23, 129(4), 137 - 40
{The development of a toxic megacolon due to Amanita phalloides poisoning . A rare complication}; Eyer F et al.; HISTORY: A 71-year-old previously healthy man consumed a mushroom meal containing Amanita phalloides, which he had confused with Agaricus campestris . Approximately 8 hours later, typical gastrointestinal symptoms began with copious loss of fluids . Treatment with penicillin G was initiated followed by a continuous silibinin infusion before the patient was transferred to our toxicological department . Other than a transient tachycardia and diffuse pain on abdominal palpation clinical examination was without abnormal findings . INVESTIGATIONS: Laboratory findings showed severe hepatic damage with 100-fold increased transaminases, elevation of serum creatinine, hyperbilirubinemia and a serious disturbance of coagulation . Infection with HIV, hepatitis- and CMV as well as pathogenic enteric bacteria and antibiotic-associated pseudo-membranous colitis were excluded . 11 days after the mushroom meal x-ray of abdomen showed a 6 cm dilatation of the small intestine and an 8 cm dilatation of the colon . DIAGNOSIS AND TREATMENT: Although clinical condition and laboratory findings nearly fulfilled transplantation criteria, hepatic injury resolved during intensive care therapy . Intractable diarrhea, dilatation of the intestine on x-ray as well as other findings met criteria of toxic megacolon . Therapy with antibiotics and systemic steroids was ineffective, so the patient needed decompression by a catheter, which was placed by colonoscopy . 30 days after the serious amanita poisoning complicated by development of toxic megacolon, the patient's condition resolved without sequelae and he was discharged . CONCLUSIONS: In addition the well known complications of amanita-poisoning, such as hepatic failure, encephalopathy and multi-organ failure, involvement of other organs like bone marrow, pancreas, kidney and gastrointestinal tract (except for the initial cholera-like gastroenteritis) are not well documented in the literature . Uncommon complications like toxic megacolon require an empirical approach.

Novartis Found Symp, 2003, 254, 43 - 50; discussion 50-6, 98-101, 250-2
Immunoinformatics in personalized medicine; Gulukota K; Diagnosis of human disease has been undergoing steady improvement over the past few centuries . Many ailments that were once considered a single entity have been classified into finer categories on the basis of response to therapy (e.g . type I and type II diabetes), inheritance (e.g . familial and non-familial polyposis coli), histology (e.g . small cell and adenocarcinoma of lung) and most recently transcriptional profiling (e.g . leukaemia, lymphoma) . The next dimension in this finer categorization appears to be the typing of the patient rather than the disease i.e . disease X in person of type Y . The problem of personalized medicine is to devise tests which predict the type of individual, especially where the type is correlated with response to therapy . Immunology has been at the forefront of personalized medicine for quite a while, even though the term is not often used in this connection . Blood grouping and cross-matching (for blood transfusion), and anaphylaxis test (for penicillin) are just two examples . In this paper I will argue that immunological tests have an important place in the future of personalized medicine . I will describe methods we developed for personalizing vaccines based on MHC allele frequencies in human populations and methods for predicting peptide binding to class I MHC molecules . In conclusion, I will argue that immunological tests, and consequently immunoinformatics, will play a big role in making personalized medicine a reality.

Appl Environ Microbiol, 2004 Jan, 70(1), 607 - 9
A complete library of amino acid alterations at N304 in Streptomyces clavuligerus deacetoxycephalosporin C synthase elucidates the basis for enhanced penicillin analogue conversion; Chin HS et al.; N304 of Streptomyces clavuligerus deacetoxycephalosporin C synthase was mutagenized to alter its catalytic ability . Given that N304A, N304K, N304L, and N304R mutant enzymes exhibited significant improvements in penicillin analogue conversions, we advocate that replacement of N304 with residues with aliphatic or basic side chains is preferable for engineering of a hypercatalytic enzyme.

Saudi Med J, 2003 Dec, 24(12), 1325 - 8
Tetanus experience in a public hospital in Western Saudi Arabia; Lubbad EH et al.; OBJECTIVE: Tetanus although rare, has not been eradicated and continues to present from time to time . Early diagnosis and management may be life saving . This study aims to evaluate all patients admitted with clinical diagnosis of tetanus in King Abdul-Aziz Hospital Jeddah, Kingdom of Saudi Arabia over the last 3 years . METHODS: All patients admitted with clinical diagnosis of Tetanus in King Abdul-Aziz Hospital and Oncology Center from January 2000 through to December 2002 were retrospectively reviewed and data was analyzed to determine the demographic features, clinical details, management, and outcome of treatment . RESULTS: A total of 11 patients were admitted during this period . All patients were diagnosed in emergency room by clinical examination . Their ages ranged from 22-68 years . The immunization status of these patients was unknown . All of them were males with 4 of them being injection-drug users . Eight patients had a definite history of injury mainly involving the lower limbs . The incubation period ranged from 5-30 days . Nine patients required mechanical ventilation for a period varying from 2-4 weeks . All patients received Tetanus Immunoglobulin with a dose ranging from 500-3000 unit . The spasms were mainly controlled by diazepam infusion with a maximum dose of 480mg/day . Magnesium sulphate was used in 6 patients to control spasms and autonomic dysfunction . Metronidazole was used in addition to benzyl penicillin in 9 patients . Out of the 11 cases 10 were discharged home and only one patient died 6 days after admission . CONCLUSION: Tetanus is still a problem in developing countries . It is a potentially fatal disease, without early medical intervention . Primary immunization and scheduled booster immunization are important preventive measures that have greatly reduced the incidence of tetanus.

J Bacteriol, 2004 Jan, 186(2), 490 - 502
Genetic analysis of the cell division protein FtsI (PBP3): amino acid substitutions that impair septal localization of FtsI and recruitment of FtsN; Wissel MC et al.; FtsI (also called PBP3) of Escherichia coli is a transpeptidase required for synthesis of peptidoglycan in the division septum and is one of several proteins that localize to the septal ring . FtsI comprises a small cytoplasmic domain, a transmembrane helix, a noncatalytic domain of unknown function, and a catalytic (transpeptidase) domain . The last two domains reside in the periplasm . We used PCR to randomly mutagenize ftsI, ligated the products into a green fluorescent protein fusion vector, and screened approximately 7,500 transformants for gfp-ftsI alleles that failed to complement an ftsI null mutant . Western blotting and penicillin-binding assays were then used to weed out proteins that were unstable, failed to insert into the cytoplasmic membrane, or were defective in catalysis . The remaining candidates were tested for septal localization and ability to recruit another division protein, FtsN, to the septal ring . Mutant proteins severely defective in localization to the septal ring all had lesions in one of three amino acids-R23, L39, or Q46-that are in or near the transmembrane helix and implicate this region of FtsI in septal localization . Mutant FtsI proteins defective in recruitment of FtsN all had lesions in one of eight residues in the noncatalytic domain . The most interesting of these mutants had lesions at G57, S61, L62, or R210 . Although separated by approximately 150 residues in the primary sequence, these amino acids are close together in the folded protein and might constitute a site of FtsI-FtsN interaction.

Am J Ophthalmol, 2004 Jan, 137(1), 101 - 8
Lacrimal canalicular bypass surgery with the Lester Jones tube; Lim C et al.; PURPOSE: To analyze outcomes of lacrimal bypass surgery with the Lester Jones tube and to determine the level of patient satisfaction . DESIGN: Interventional case series . METHODS: We retrospectively analyzed the outcomes of 49 patients (42 patients) who underwent conjunctivodacryocystorhinostomy between 1984 and 2002 . Data were obtained from medical records, semistructured phone interviews, and written questionnaires . RESULTS: The causes of lacrimal obstruction were idiopathic and trauma, congenital agenesis, infection, inflammation, herpes, basal cell carcinoma, radiation therapy, penicillin-induced Steven-Johnsons syndrome, systemic chemotherapy, and facial nerve palsy . Patients had undergone previous failed lacrimal surgery in 21% of cases . Complete or significant improvement of epiphora was achieved in 94% of cases . Best results were obtained for trauma and herpetic obstruction . Complications were frequent and included extrusion, recurrent extrusion, malposition, obstruction, discomfort, infection, and diplopia . Of the 32 patients who were interviewed, 70% were satisfied with the result, 35% reported tube maintenance to be troublesome, and all patients were pleased with the esthetics of the Jones tube . CONCLUSIONS: Conjunctivodacryocystorhinostomy with the insertion of a Jones tube can be expected to improve epiphora significantly in most cases and remains the standard treatment for canalicular obstruction . Complications occur in most cases, requiring replacement, repositioning, and cleaning of the tube by the ophthalmologist over an indefinite period of time . Despite frequent complications, patients will usually be satisfied if they obtain a comfortable, dry eye . If, however, a completely dry eye is not achieved, frequent complications may contribute to patient dissatisfaction.

J Chromatogr B Analyt Technol Biomed Life Sci, 2004 Feb 5, 800(1-2), 203 - 9
Capillary electrophoresis method for simultaneous determination of penicillin G, procaine and dihydrostreptomycin in veterinary drugs; Michalska K et al.; Capillary electrophoresis method for identification and simultaneous determination of procaine, dihydrostreptomycin and penicillin G, present in multiantibiotic veterinary preparations, was elaborated . The influence of pH (5.0-9.75) and concentration of disodium tetraborate decahydrate in running buffers (0.02-0.1 M) as well as temperatures (25-40 degrees C) on separation efficacy were analyzed . For quantitative analysis, 0.08 M borate buffer (pH 8.0) at 35 degrees C and 15 kV were chosen . Method was validated, selectivity, precision, linearity, LOD, LOQ, accuracy and specificity of capillary zone electrophoresis (CZE) were evaluated.

Antimicrob Agents Chemother, 2004 Jan, 48(1), 192 - 202
Five additional genes are involved in clavulanic acid biosynthesis in Streptomyces clavuligerus; Jensen SE et al.; An approximately 12.5-kbp region of DNA sequence from beyond the end of the previously described clavulanic acid gene cluster was analyzed and found to encode nine possible open reading frames (ORFs) . Involvement of these ORFs in clavulanic acid biosynthesis was assessed by creating mutants with defects in each of the ORFs . orf12 and orf14 had been previously reported to be involved in clavulanic acid biosynthesis . Now five additional ORFs are shown to play a role, since their mutation results in a significant decrease or total absence of clavulanic acid production . Most of these newly described ORFs encode proteins with little similarity to others in the databases, and so their roles in clavulanic acid biosynthesis are unclear . Mutation of two of the ORFs, orf15 and orf16, results in the accumulation of a new metabolite, N-acetylglycylclavaminic acid, in place of clavulanic acid . orf18 and orf19 encode apparent penicillin binding proteins, and while mutations in these genes have minimal effects on clavulanic acid production, their normal roles as cell wall biosynthetic enzymes and as targets for beta-lactam antibiotics, together with their clustered location, suggest that they are part of the clavulanic acid gene cluster.

Int J Infect Dis, 2004 Jan, 8(1), 47 - 51
Implementation of clinical practice guidelines for upper respiratory infection in Thailand; Thamlikitkul V et al.; OBJECTIVE: To determine the effectiveness of implementing clinical practice guidelines (CPG) on antibiotic prescribing for adults with upper respiratory infection (URI) in terms of the changes in diagnosis and prevalence and patterns of antibiotic prescribing . METHODS: The CPG on antibiotic treatments for adults with URI published in the Annals of Internal Medicine 2001; 134: 479-52 were considered to be of high quality and applicable to Thai patients . A one-page clinical practice protocol in Thai was prepared from these guidelines . The dissemination strategy provided CPG and clinical practice protocol to 12 general practitioners in Siriraj Social Security Program in Bangkok during interactive educational meetings in April 2001 . The information on 837 URI episodes from January to March (pre-CPG phase) and 774 URI episodes during May to July (post-CPG phase) were extracted from the patients' medical records . Telephone follow up for patients without antibiotics in the post-CPG phase was also attempted . RESULTS: Changes in the post-CPG period included (1) The diagnosis of URI was used less frequently whereas the diagnosis of common cold, pharyngitis and acute bronchitis were used more frequently (p<0.05) . (2) Antibiotic use fell from 74.0% to 44.1% (p<0.001) . (3) Fewer prescriptions for amoxicillin, roxithromycin, co-trimoxazole and doxycycline, and more for penicillin V (p<0.05) . Patients (n=97) not given antibiotics reported recovery in 83.5% and improvement in 16.5% . CONCLUSION: A locally prepared clinical practice protocol based on US CPG for appropriate antibiotic use for URI combined with interactive educational meetings is effective in promoting appropriate diagnosis and antibiotic therapy in an ambulatory setting in a tertiary care hospital in Thailand.

Internist (Berl), 2003 Dec, 44(12), 1575 - 8
{"Peculiar infection" with fever, splenomegaly and acute kidney failure in a 24-year-old forestry student}; Strutz F et al.; When confronted by the combination of initial high fever associated with intense malaise, splenomegaly, elevated levels of transaminases, and acute renal failure, consideration must be given to the differential diagnosis of leptospirosis even in Germany . As a rule, the diagnosis is confirmed by serological testing based on the titer curve . Renal involvement is frequent, but usually has a good prognosis, especially if jaundice has not developed . Treatment with doxycycline or penicillin can shorten the disease course and exudation, possibly also the nephritis, or hinder it.

Chin Med J (Engl), 2003 Dec, 116(12), 1904 - 10
Detection of specific IgE antibodies to major and minor antigenic determinants in sera of penicillin allergic patients; Zhao Y et al.; OBJECTIVE: To investigate the mechanism(s) of penicillins allergic reaction . METHODS: The radioallergosorbent test (RAST) was used to detect 9 specific IgE antibodies, including major antigenic determinants: benzylpenicilloyl (BPO), ampicilloyl (APO), amoxicilloyl (AXO), phenoxomethylpenicilloyl (PVO) and flucloxacilloyl (FLUO), and minor antigenic determinants: benzylpenicillanyl (BPA), amoxicillanyl (AXA), 6-aminopenicillanic (APA) and phenoxomethylpenicillany (PVA), in the sera of 32 penicillin allergic patients . The relationship between specific IgE antibodies and penicillins chemical structures was studied by radioallergosorbent inhibition test . RESULTS: Nineteen of 32 patients (59.4%) were RAST positive, among whom, five cases were positive only to one or two antigenic minor determinants, and three cases were positive only to one or three major antigenic determinants . The remaining 11 patients were positive not only to major antigenic determinants but also minor antigenic determinants . In 9 specific IgE antibodies, the positive rate of PVA-IgE was the highest (34.38%), followed by BPO-IgE (31.25%) . The positive rate of FLUO-IgE was the lowest (15.63%) . Of the total patient group, 53.13% were positive to one or more minor antigenic determinants, while 37.5% (12/32) were positive to one or more major antigenic determinants . The percentage of patients with urticarial reactions who were positive to minor antigenic determinants (63.16%) was significantly higher than observed in the anaphylactic shock group (38.5%, P < 0.05) . CONCLUSIONS: The minor antigenic determinant was important in allergic reaction . The combining sites of the specific IgE antibodies were likely to be the side-chain of drug or the overwhelming drug molecule.

Patol Fiziol Eksp Ter, 2003 Oct-Dec, (4), 11 - 3
{Formation of nitric oxide by peripheral blood leukocytes in the norm and in pathology}; Golikov PP et al.; The study was made of nitric oxide (NO) generation by leukocytes of peripheral blood from healthy subjects and patients with a compound trauma . How to isolate leukocytes from the whole blood is shown . Leukocyte isolation rate reached 98% . Generation of NO by leukocytes was made in the medium containing medium RPMI 1640 (free of phenol red), calf embryonic serum (5%), L-glutamine (2 mM), gentamycin (80 mcg/ml), penicillin (100 U/ml), streptomycin (100 mcg/ml) . Incubation lasted for 15 h at 37 degrees in tissue culture plates with 24 cells 16 mm in diameter (Costor, USA) . NO generation was defined in supernatants of cultivated leukocytes (5 x 10(6)) with Griss reagent in reaction with stable metabolite nitrite . NO content among the leukocytes from healthy subjects was 0.63 +/- 0.08 nmol, in trauma 1.10 +/- 0.08 nmol, relative production of NO by healthy subjects was 1.27 +/- 0.17 mumol/l, in trauma 2/21 +/- 0.18 mumol/l, absolute production was 0.99 +/- 0.15 mumol/l and 1.98 +/- 0.19 mumol/l, respectively . The findings point to an important role of nitric oxide generation by leukocytes in reaction with superoxide radical in production of peroxynitrite responsible for severity of endotoxicity.

Ned Tijdschr Geneeskd, 2003 Nov 29, 147(48), 2382 - 5
{Unavoidable surgical intervention in two women with severe actinomycosis during IUD use}; Bergenhenegouwen LA et al.; Extensive abdominal infections with Actinomyces were diagnosed in two women aged 35 and 33 years respectively, who suffered from the nonspecific symptoms fever and abdominal pain . These infections occur more often in women with an intrauterine device . Development of an abdominal mass with ureter or bowel obstruction may cause hydronephrosis and mechanical ileus . The patients underwent a laparotomy and a double-J catheter was inserted, which could be removed later on (temporary stoma) . Treatment included high-dose penicillin i.v . followed by oral amoxicillin . Both patients recovered . It may be difficult to establish this diagnosis: the first patient was diagnosed by histopathological examination, in the second Actinomyces had been found in a routine cervical smear a few years earlier.

Cancer Chemother Pharmacol, 2004 Mar, 53(3), 276 - 7 Epub 2003 Dec 16.
Two potential mechanisms of oxaliplatin-induced haemolytic anaemia in a single patient; Hofheinz RD et al.; Only two patients with adequately documented oxaliplatin-induced autoimmune haemolytic anaemia have previously been reported . We report here a third patient with an immune-haematological finding favouring a bispecific mechanism (immune-complex and penicillin type) of oxaliplatin-induced haemolysis.

Oral Surg Oral Med Oral Pathol Oral Radiol Endod, 2003 Dec, 96(6), 685 - 94
The efficacy and safety of 50 mg penicillin G potassium troches for recurrent aphthous ulcers; Kerr AR et al.; PURPOSE: To determine both the efficacy and safety of the topical application of 50 mg penicillin G potassium troches (Cankercillin) in the treatment of minor recurrent aphthous stomatitis (RAS) . STUDY DESIGN: The investigation used a phase 2 double-blind, randomized placebo-controlled trial with a no-treatment arm . Subjects with minor aphthous ulcers of duration <48 hours were followed for 1 week . The primary endpoint for efficacy was time (days) to complete ulcer resolution, and the secondary endpoint was time (days) to complete pain relief . RESULTS: Thirty-one, 33, and 36 subjects were randomized to the active treatment, placebo, and no-treatment arms, respectively . Baseline findings were heterogeneous across arms . Subjects who received penicillin G treatment had complete ulcer healing and pain relief significantly earlier than those in the placebo and no-treatment arms . No allergic reactions were observed . CONCLUSIONS: Topical penicillin G, by mechanisms which remain unclear, reduces the time of healing and pain relief of minor aphthous ulcers with minimal safety concerns . Larger phase 3 studies are necessary to confirm these findings.

Arch Dis Child, 2003 Dec, 88(12), 1070 - 5
An observational study to detect leptospirosis in Mumbai, India, 2000; Karande S et al.; BACKGROUND: Leptospirosis is relatively uncommon in children . Following torrential rains and flooding an outbreak of leptospirosis was suspected in Mumbai . AIMS: To investigate the possibility of an outbreak of leptospirosis and describe the clinical illness . METHODS: From 24 July to 14 September 2000, children with a history of abrupt onset of high fever (>39 degrees C), who presented to our hospital, were admitted and tested serologically for anti-Leptospira antibodies by a quantitative enzyme linked immunosorbent assay (ELISA) test . An IgM titre of more than 20U/ml confirmed the diagnosis of leptospirosis . Clinical features in the confirmed leptospirosis and leptospirosis negative groups were analysed . RESULTS: Of 53 children screened, 18 (34%) had leptospirosis . In all 18, the disease was anicteric and responded well to intravenous penicillin . Four clinical features present at the time of admission were significantly associated with leptospirosis: a history of contact with flood water (18/18 v 16/35), conjunctival suffusion (5/18 v 1/35), abdominal pain (9/18 v 5/35), and skin rash (5/18 v 1/35) . As the number of these four features concomitantly present increased, the chances of the child having leptospirosis also increased significantly . A history of contact with flood water had a sensitivity of 100%, and the presence of conjunctival suffusion, abdominal pain, and skin rash had a specificity of 97%, 86%, and 97%, respectively, for identifying children with leptospirosis . CONCLUSION: Leptospirosis should be suspected in febrile children with contact with flood water.

Curr Opin Microbiol, 2003 Dec, 6(6), 594 - 9
Role of penicillin-binding proteins in bacterial cell morphogenesis; Popham DL et al.; The penicillin-binding proteins (PBPs) polymerize and modify peptidoglycan, the stress-bearing component of the bacterial cell wall . As part of this process, the PBPs help to create the morphology of the peptidoglycan exoskeleton together with cytoskeleton proteins that regulate septum formation and cell shape . Genetic and microscopic studies reveal clear morphological responsibilities for class A and class B PBPs and suggest that the mechanism of shape determination involves differential protein localization and interactions with specific cell components . In addition, the low molecular weight PBPs, by varying the substrates on which other PBPs act, alter peptidoglycan synthesis or turnover, with profound effects on morphology.

Theriogenology, 2004 Jan 15, 61(2-3), 373 - 80
In vitro maturation, fertilization and early cleavage rates of bovine fetal oocytes; Chohan KR et al.; The in vitro developmental competence of oocytes harvested from 3 to 6 mm follicles from ovaries of 7.5 months to term fetuses and adult cows was compared . Cumulus oocyte complexes (COCs) were washed and placed in 200 microl droplets of maturation medium 199, supplemented with 10 microg/ml FSH, 10 microg/ml LH, 1.5 microg/ml estradiol, 75 microg/ml streptomycin, 100 IU/ml penicillin, 10 mM Hepes, and 10% fetal bovine serum (FBS) under oil and incubated for 24 h at 39 degrees C and 5% CO2 . Matured oocytes were exposed to frozen-thawed TALP swim-up, heparin-capacitated sperm (20 h, 39 degrees C, 5% CO2) . Presumptive zygotes were cultured in medium 199 containing 8 mg/ml BSA-V, 100 IU/ml penicillin G, 75 microg/ml streptomycin, and 10 mM Hepes (48 h, 39 degrees C, 5% CO2) . Oocytes/embryos were fixed, stained with DAPI, and evaluated under fluorescent microscopy to assess maturation, fertilization, and subsequent embryonic development . There was a difference (P<0.05) between fetal and adult cow oocytes for in vitro maturation (IVM; 80.1% versus 92.0%), fertilization (69.3% versus 79.9%), and cleavage rates (36.7% versus 49.9%), respectively . Poor IVM, fertilization and embryonic development of fetal oocytes may be due to a higher incidence of blockage at germinal vesicle (GV) and metaphase-I (M-I) stage after IVM (12.0% versus 2.3% for fetal versus adult oocytes, respectively, P<0.05) . Although the IVF results with fetal oocytes are poorer than with adult cow oocytes, they were still high enough to be considered for use in research and when death of the dam and/or fetus is pre-mature or sudden.

Trends Microbiol, 2003 Dec, 11(12), 547 - 53
Cell wall branches, penicillin resistance and the secrets of the MurM protein; Fiser A et al.; Production of low-affinity forms of penicillin-binding proteins (PBPs), although essential, is not sufficient to protect pneumococci against the inhibitory action of penicillin . Resistance also requires the newly identified protein MurM which, together with MurN, is involved with the synthesis of short peptide branches in the pneumococcal cell wall . Cells in which murM was inactivated produced cell walls without branches and also completely lost penicillin resistance . To understand these surprising observations a 3D-model of MurM was constructed, which helped to put into structural context several of the biochemical and genetic observations made about this protein.

Biotechnol Prog, 2003 Nov-Dec, 19(6), 1639 - 42
Improving the industrial production of 6-APA: enzymatic hydrolysis of penicillin G in the presence of organic solvents; Abian O et al.; The hydrolysis of penicillin G in the presence of an organic solvent, used with the purpose of extracting it from the culture medium, may greatly simplify the industrial preparation of 6-APA . However, under these conditions, PGA immobilized onto Eupergit displays very low stability (half-life of 5 h in butanone-saturated water) and a significant degree of inhibition by the organic solvent (30%) . The negative effect of the organic solvent strongly depended on the type of solvent utilized: water saturated with butanone (around 28% v/v) had a much more pronounced negative effect than that of methylisobutyl ketone (MIBK) (solubility in water was only 2%) . These problems were sorted out by using a new penicillin G acylase derivative designed to work in the presence of organic solvents (with each enzyme molecule surrounded by an hydrophilic artificial environment) and a suitable organic solvent (MIBK) . Using such solvent, this derivative kept its activity unaltered for 1 week at 32 degrees C . Moreover, the enzyme activity was hardly inhibited by the presence of the organic solvent . In this way, the new enzyme derivative thus prepared enables simplification of the industrial hydrolysis of penicillin G.

J Pediatr (Rio J), 2001 Jan-Feb, 77(1), 52 - 4
{Pediatric cervicofacial actinomycosis - case report and review of the literature}; Bononi F et al.; OBJECTIVE: To emphasize important features in the diagnosis and monitoring of patients with childhood cervical actinomycosis . SUBJECT AND METHODS: We report the case of a patient with cervicofacial actinomycosis . We also carried out a review of the literature from the past few years (Lilacs and Medline) . RESULTS: We followed a male patient admitted to the pediatric infectious disease ward . Diagnosis was carried out through biopsy of a cervical node and isolation of bacteria . Specific penicillin treatment for actinomycosis was administered for 14 days . Subsequently, we observed remission of the node . The patient was discharged from the hospital . At least 6 months of amoxycillin therapy with simultaneous outpatient follow-up were recommended . CONCLUSION: Early diagnosis of actinomycosis enables appropriate and prompt treatment, thus preventing the involvement of other areas such as CNS, face, and neck.

Biotechnol Appl Biochem . 2003 Nov 28; {Epub ahead of print}
Mannan-penicillin G acylase neoglycoproteins and their potential applications in biotechnology; Masarova J et al.; Mannan-penicillin G acylase neoglycoproteins were prepared by the conjugation of Saccharomyces cerevisiae mannan with enzyme penicillin G acylase using reductive amination method . Eight neoglycoproteins preparations were obtained after gel chromatography . The preparations contained from 42 % to 67 % (w/w) saccharides and their molar masses varied from 283 kDa to above 10 3 kDa . Significant biospecific interaction of separated fractions with lectin Concanavalin A was evaluated by precipitation and sorption method (equilibrium constants) and further characterized using surface plasmon resonance method to determine kinetic association and dissociation constants . K D was determined in the range 10 -7 mol.L -1 . High molar mass preparations appeared to be more suitable for preparation of stable and active complex with Con A for prospective use as PGA biocatalyst in enzyme reactors . The enzyme stability of such complex was significantly increased compare to original neoglycoprotein . Lower molar mass preparations are more suitable for applications as biocatalysts in bioanalytical devices.

Zhongguo Ji Sheng Chong Xue Yu Ji Sheng Chong Bing Za Zhi, 2003, 21(3), 176 - 8
{Preliminary study on primary culture of cells from Oncomelania hupensis}; Peng-Yan et al.; OBJECTIVE: To study the primary culture of cells from Oncomelania hupensis . METHODS: After washed in the sterile solution with antibiotic, the Oncomelania hupensis snails and their eggs were dissected . The soft tissue, liver, mantle and the embryo were collected and torn up respectively . Above tissues except mantle were digested by a mixture containing equal volumes of 0.25% trypsin and 0.02% EDTA for several hours at 4 degrees C . The cells after digestion were inoculated . Meanwhile, the tissue of mantle were inoculated by moist system method . All cells were cultured separately in medium 1/2 RP-MI1640 containing 20% calf serum and antibiotics (penicillin G 100 IU/ml, streptomycin 100 micrograms/ml) at pH 7.2-7.4 and temperature of 27 degrees C-28 degrees C . RESULTS: After the embryonic tissue was digested by tryspin/EDTA mixture, lots of dissociated cells were obtained . Some of the cells began to adhere to the culture flask surface after cultured for 5 days . The adhering cells were flat and polygonal, about(15-20 x 12-15) micron in diameter . But most of the cells were still suspending in the media . The suspending cells were round, usually about 8-12 microns in diameter with a few reaching 30-35 microns in diameter . These cells grew well and could be subcultured . CONCLUSION: Embryonic cells from Oncomelania hupensis can be primarily cultured and subcultured.

Mol Microbiol, 2003 Nov, 50(4), 1199 - 213
Characterization of the hipA7 allele of Escherichia coli and evidence that high persistence is governed by (p)ppGpp synthesis; Korch SB et al.; The ability of a high frequency (10(-2)) of Escherichia coli to survive prolonged exposure to penicillin antibiotics, called high persistence, is associated with mutations in the hipA gene . The hip operon is located in the chromosomal terminus near dif and consists of two genes, hipA and hipB . The wild-type hipA gene encodes a toxin, whereas hipB encodes a DNA-binding protein that autoregulates expression of the hip operon and binds to HipA to nullify its toxic effects . We have characterized the hipA7 allele, which confers high persistence, and established that HipA7 is non-toxic, contains two mutations (G22S and D291A) and that both mutations are required for the full range of phenotypes associated with hip mutants . Furthermore, expression of hipA7 in the absence of hipB is sufficient to establish the high persistent phenotype, indicating that hipB is not required . There is a strong correlation between the frequency of persister cells generated by hipA7 strains and cell density, with hipA7 strains generating a 20-fold higher frequency of persisters as cultures approach stationary phase . It is also demonstrated that relA knock-outs diminish the high persistent phenotype in hipA7 mutants and that relA spoT knock-outs eliminate high persistence altogether, suggesting that hipA7 facilitates the establishment of the persister state by inducing (p)ppGpp synthesis . Consistent with this proposal, ectopic expression of relA' from a plasmid was shown to increase the number of persistent cells produced by hipA7 relA double mutants by 100-fold or more . A model is presented that postulates that hipA7 increases the basal level of (p)ppGpp synthesis, allowing a significantly greater percentage of cells in a population to assume a persistent, antibiotic-insensitive state by potentiating a rapid transition to a dormant state upon application of stress.

J Am Vet Med Assoc, 2003 Nov 1, 223(9), 1283 - 92
Multicenter case-control study of risk factors associated with development of vaccine-associated sarcomas in cats; Kass PH et al.; OBJECTIVE: To determine whether particular vaccine brands, other injectable medications, customary vaccination practices, or various host factors were associated with the formation of vaccine-associated sarcomas in cats . DESIGN: Prospective multicenter case-control study . ANIMALS: Cats in the United States and Canada with soft tissue sarcomas or basal cell tumors . PROCEDURE: Veterinarians submitting biopsy specimens from cats with a confirmed diagnosis of soft tissue sarcoma or basal cell tumor were contacted for patient medical history . Time window statistical analyses were used in conjunction with various assumptions about case definitions . RESULTS: No single vaccine brand or manufacturer within antigen class was found to be associated with sarcoma formation . Factors related to vaccine administration were also not associated with sarcoma development, with the possible exception of vaccine temperature prior to injection . Two injectable medications (long-acting penicillin and methyl prednisolone acetate) were administered to case cats more frequently than to control cats . CONCLUSIONS AND CLINICAL RELEVANCE: Findings do not support the hypotheses that specific brands or types of vaccine within antigen class, vaccine practices such as reuse of syringes, concomitant viral infection, history of trauma, or residence either increase or decrease the risk of vaccine-associated sarcoma formation in cats . There was evidence to suggest that certain long-acting injectable medications may also be associated with sarcoma formation.

Am J Vet Res, 2003 Nov, 64(11), 1360 - 3
Evaluation of the effects of penicillin G potassium and potassium chloride on the motility of the large intestine in horses; Roussel AJ et al.; OBJECTIVE: To evaluate effects of IV administration of penicillin G potassium (KPEN) or potassium chloride (KCl) on defecation and myoelectric activity of the cecum and pelvic flexure of horses . ANIMALS: 5 healthy horses . PROCEDURE: Horses with 12 bipolar electrodes on the cecum and pelvic flexure received KPEN or KCl solution by IV bolus 4 hours apart . Each horse received the following: 2 X 10(7) U of KPEN (high-dose KPEN) followed by 34 mEq of KCl (high-dose KCl), 1 X 10(7) U of KPEN (low-dose KPEN) followed by 17 mEq of KCl (low-dose KCl), high-dose KCl followed by high-dose KPEN, and low-dose KCl followed by low-dose KPEN . Number of defecations and myoelectric activity were recorded for 60 minutes . The first three 5-minute segments and first four 15-minute segments of myoelectric activity were analyzed . RESULTS: Number of defecations during the first 15-minute segment was greater after high-dose KPEN treatment than after high-dose or low-dose KCl treatment . Compared with reference indexes, myoelectric activity was greater in the pelvic flexure for the first 5-minute segment after high-dose KCl treatment, in the cecum and pelvic flexure for the first 5-minute segment and in the pelvic flexure for the first 15-minute segment after low-dose KPEN treatment, and in the pelvic flexure for the first and second 5-minute segments and the first three 15-minute segments after high-dose KPEN treatment . CONCLUSIONS AND CLINICAL RELEVANCE: IV administration of KPEN stimulates defecation and myoelectric activity of the cecum and pelvic flexure in horses . Effects of KPEN may be beneficial during episodes of ileus.

Am Fam Physician, 2003 Nov 1, 68(9), 1781 - 90
Adverse drug reactions: types and treatment options; Riedl MA et al.; Drug hypersensitivity results from interactions between a pharmacologic agent and the human immune system . These types of reactions constitute only a small subset of all adverse drug reactions . Allergic reactions to medications represent a specific class of drug hypersensitivity reactions mediated by IgE . Immune-mediated drug reactions may be discussed generally in the Gell and Coombs classification system, a widely accepted conceptual framework for understanding complex immune reactions . However, some reactions involve additional, poorly understood mechanisms that are not easily classified . Identifiable risk factors for drug hypersensitivity reactions include age, female gender, concurrent illnesses, and previous hypersensitivity to related drugs . Drug hypersensitivity is a clinical diagnosis based on available data . Laboratory testing may be useful, with skin testing providing the greatest specificity . Treatment is largely supportive and includes discontinuation of the offending medication, symptomatic treatment, and patient education . Patients with penicillin allergy should avoid carbapenems, and caution should be used in prescribing cephalosporins in these patients . Reactions to radiocontrast media can be limited by pretreatment with prednisone, diphenhydramine, and either ephedrine or a histamine H2-receptor antagonist.

J Vet Sci, 2001 Aug, 2(2), 121 - 4
Therapeutic effect of bee venom in sows with hypogalactia syndrome postpartum; Choi SH et al.; The objective of this study was to determine the clincotherapeutic effect of whole bee venom in hypogalactic sows postpartum . Sows after parturition were assigned to treated and nontreated control groups . In the treated group, 22 sows were bee acupunctured once a day for 3 consecutive days . Honeybees (Apis mellifera L.) for bee acupuncture were about 15 days after metamorphosis . One live bee was used to sting the acupoints known as Yang-ming (ST-18, 1.5 cm lateral to the base of the last 2 pairs of teats) and Jiao-chao (GV-1, at the indentation between the base of tail and the anus) . In the control group, 20 sows were intramuscularly injected with a standard dosage of penicillin G (400,000 IU/head) once a day for 3 consecutive days . At post-treatment, 85.0% of the drug-treated control and 90.9% of the bee venomtreated group recovered from hypogalactia syndrome . The advantages of apitherapy were that the patients did not have stress because they were not restrained for a long period . The result suggested that apitherapy using bee venom is an effective treatment for sows with hypogalactia syndrome postpartum.

Acta Derm Venereol, 2003, 83(5), 365 - 8
Short-time, high-dosage penicillin infusion therapy of syphilis: an alternative to recommended regimens?
Lomholt H, Poulsen A, Brandrup F, Andersen KE.
The optimal dosage and duration of penicillin treatment for the various stages of syphilis are not known . We present data on 20 patients with syphilis (primary, secondary or latent) treated with high-dose, short-time penicillin infusion therapy . Patients were given 10 MIU of penicillin G intravenously every 6 h up to a total dose of 90 MIU within 48 h . No adverse reactions were registered but 9 patients showed a Herxheimer reaction . Four patients were lost to follow-up and the remaining 16 were serologically and clinically followed for mean 18.5 months (range 3-36) . During this period, the Wassermann reaction turned negative for 12 patients and was reduced more than fourfold for the rest, with one exception . None of the patients showed clinical signs of active syphilis following treatment . The cerebrospinal fluid penicillin concentration was measured in one patient during treatment and found to be much higher than the minimally treponemacidal concentration generally recommended . The treatment modality is reviewed and discussed and it may provide an alternative to conventional treatment regimens of early syphilis.

Int J Biol Macromol, 2003 Dec, 33(4-5), 159 - 66
Penicillin degradation catalysed by Zn(II) ions in methanol; Navarro PG et al.; The rates of degradation, catalysed by Zn(2+), of four classical penicillins-amoxicillin, ampicillin and penicillins G and V-were followed at 20 degrees C in methanol by spectrophotometric assays . Kinetic schemes of the reactions of degradation catalysed by Zn(2+) ions were analogous to those given previously for the reaction catalysed by Cd(2+) ions . The methanolysis of penicillin V occurs with the formation of a single intermediate substrate-metal complex (SM), whereas the degradations of amoxicillin, ampicillin and penicillin G occur with the initial formation of two complexes with different stoichiometry, SM and S(2)M, both in equilibrium . In all cases, the degradation reaction is of the first order with respect to SM, with velocity constants at 20 degrees C of 0.0093, 0.0288, 0.0304 and 0.0349 min(-1), for amoxicillin, ampicillin, penicillin V and penicillin G, respectively . The compound S(2)M degraded at a much lower rate than SM and constitutes a zero-order process . The catalytic effect of the ion Zn(2+) in the degradation of the penicillins was much weaker than that of the ion Cd(2+), owing to the lesser ionic radius of the former and the fact that in the case of the reaction catalysed by Zn(2+), the compound S(2)M occurred in a much greater amount than the SM . At the end of the degradation reaction, the corresponding penamaldic derivative of the antibiotic was produced, established by the coordination of the Zn(2+) ion, forming a single complex 2:1 (derivative penamaldic-metal) in the case of amoxicillin and ampicillin; and two complexes, 1:1 and 2:1, for the other antibiotics . Finally, the molar absorption coefficients of the products of reaction at the wavelength of maximum absorption at 20 degrees C were calculated.

Biomacromolecules, 2003 Nov-Dec, 4(6), 1495 - 501
Novel bifunctional epoxy/thiol-reactive support to immobilize thiol containing proteins by the epoxy chemistry; Grazu V et al.; In this manuscript, we present a new bifunctional support containing epoxide and thiol-reactive groups for its use in protein immobilization . In a first step, the proteins are reversibly immobilized by reaction of its thiol groups with the thiol-reactive groups of the support under mild experimental conditions (pH 7.0, 24 degrees C) . Then, the remaining epoxides of the support can form irreversible bonds with nucleophile surface groups of the already immobilized protein in a rapid way . The partial derivatization of EP-Sepabeads (a commercial matrix containing 120 micromol epoxy groups/g drained support) was optimized, using dithiotreitol (DTT) as thiolating agent . It was possible to achieve a partial thiolation of the support proportional to the concentration of DTT used (3, 8, and 15 micromol SH groups/g wet support) . The remaining epoxide content after the thiolation treatment was high (e.g., nearly 70% for the highest thiolation degree) . High immobilization yields were obtained for the three model enzymes selected (60% for Penicillin G acylase, 65% and 100% for K . lactis and E . coli beta-galactosidase, respectively) . In all cases, no significant immobilization onto an unmodified epoxy support was found, thus demonstrating that the first step of attachment takes place through thiol-disulfide exchange reactions . In the case of the bifunctional support, progressive formation of enzyme-support attachments involving the epoxy groups was showed by the irreversible covalent attachment of the proteins on the support . The promotion of this multipoint covalent immobilization required long incubation periods at basic pH values.

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