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 penicill