Penicillin

J Pharmacol Exp Ther, 2002 Aug, 302(2), 666 - 71
Characterization of methotrexate transport and its drug interactions with human organic anion transporters; Takeda M et al.; Life-threatening drug interactions are known to occur between methotrexate and nonsteroidal anti-inflammatory drugs (NSAIDs), probenecid, and penicillin G . The purpose of this study was to characterize methotrexate transport, as well as to determine the site and the mechanism of drug interactions in the proximal tubule . Mouse proximal tubule cells stably expressing basolateral human organic anion transporters (hOAT1 and hOAT3) and apical hOAT (hOAT4) were established . The K(m) values for hOAT1-, hOAT3-, and hOAT4-mediated methotrexate uptake were 553.8 microM, 21.1 microM, and 17.8 microM, respectively . NSAIDs (salicylate, ibuprofen, ketoprofen, phenylbutazone, piroxicam, and indomethacin), probenecid, and penicillin G dose dependently inhibited methotrexate uptake mediated by hOAT1, hOAT3, and hOAT4 . Kinetic analysis of inhibitory effects of these drugs on hOAT3-mediated methotrexate uptake revealed that these inhibitions were competitive . The K(i) values for the effects of salicylate, phenylbutazone, indomethacin, and probenecid on hOAT3-mediated methotrexate uptake were comparable with therapeutically relevant plasma concentrations of unbound drugs . In addition, in the presence of human serum albumin, the K(i) values were comparable with therapeutically relevant total plasma concentrations of drugs . In conclusion, these results suggest that methotrexate is taken up via hOAT3 and hOAT1 at the basolateral side of the proximal tubule and effluxed or taken up at the apical side via hOAT4 . In addition, hOAT1, hOAT3, and hOAT4 are the sites of drug interactions between methotrexate and NSAIDs, probenecid, and penicillin G . Furthermore, it was predicted that hOAT3 is the site of drug interactions between methotrexate and salicylate, phenylbutazone, indomethacin, and probenecid in vivo.

Bull Exp Biol Med, 2002 Apr, 133(4), 334 - 5
Protective effect of copper-rutin complex in animals with experimental epilepsy; Tsaryuk VV et al.; Copper-rutin complex (2 mg/kg) completely eliminated epileptiform potentials induced by a combination of chlorpromazine and microwave radiation 1-2 min postinjection and suppressed convulsive activity provoked by application of penicillin to the sensorimotor cortex.

Antimicrob Agents Chemother, 2002 Aug, 46(8), 2716 - 9
Activities of ABT-773 against microaerophilic and fastidious organisms; Finegold SM et al.; ABT-773 was tested against 317 fastidious isolates; it inhibited 99% of organisms at a concentration of 4.0 microg/ml . With ampicillin-sulbactam and levofloxacin, only 2 and 6% of these strains, respectively, were resistant at the breakpoint . With clindamycin, penicillin G, and metronidazole, 22, 26, and 58% of the strains, respectively, were resistant.

Clin Experiment Ophthalmol, 2002 Aug, 30(4), 297 - 9
Rapid seroconversion to Treponema pallidum and HIV positivity in a patient with retinal vasculitis; Venkatesh P et al.; A patient with idiopathic retinal vasculitis was found to have rapid conversion of serological tests for Treponema pallidum and HIV . The diagnosis was confirmed by Venereal Disease Research Laboratory (VDRL) testing and dark ground illumination for T . pallidum, and enzyme-linked immunosorbent assay (ELISA) and Western blot assay tests for HIV . Following treatment with intravenous penicillin, the fundus lesions resolved and visual acuity recovered from inaccurate light projection to 6/24 in the right eye and from counting fingers close to face to 2/60 in the left eye . Serological tests for T . pallidum in patients with concurrent HIV infection may be unpredictable . Hence, it is important to repeat these tests even in the early treatment phase of patients with retinal vasculitis who have shown initial seronegativity . This enables earlier diagnosis and initiation of specific treatment.

Infection, 2002 Jun, 30(3), 175 - 7
Brachyspira (Serpulina) pilosicoli spirochetemia in an immunocompromised patient; Kanavaki S et al.; The case of an elderly immunocompromised man with non-Hodgkin's lymphoma who presented with fever, abdominal pain and bloody diarrhea is described . Brachyspira pilosicoli was isolated from culture . The patient was treated with penicillin G i.v . and became afebrile . B . pilosicoli is a recently recognized enteric pathogen of humans and animals . Intestinal spirochetosis should be included in the differential diagnosis of any immunocompromised or critically ill patient with dysentery.

Infection, 2002 Jun, 30(3), 150 - 6
Effect of dexamethasone and pentoxifylline in combination with amoxicillin in the treatment of penicillin-insensitive pneumococcal pneumonia in guinea pigs; Parra A et al.; A fatal guinea pig model of pneumococcal pneumonia was developed in order to evaluate the efficacy of amoxicillin combined with either pentoxifylline or dexamethasone . Parameters assessed were survival time and lung changes (alterations, bacterial colony counts, inducible nitric oxide synthase {iNOS} and cyclooxygenase-2 {COX-2} protein expression) . Animals receiving pentoxifylline (50 mg/kg) showed higher survival rates than controls (p < 0.05) . Animals which received amoxicillin (50 mg/kg), alone or combined, showed significantly higher survival rates than controls (p < 0.05) . Animals dying in spite of receiving amoxicillin alone or combined had lung colony counts significantly lower than those that did not receive the antibiotic (p < 0.001), but their lungs showed identical changes . The correlation between COX-2 protein expression and mortality was rather high (r = 0.75) . The addition of either dexamethasone or pentoxifylline to amoxicillin improved neither survival rates nor lung pathology when compared with the antibiotic alone.

J Pediatr, 1974 Jan, 84(1), 49 - 54
Febrile illness in early infancy associated with ECHO virus infection; Linnemann CC Jr et al.; Twenty-three infants less than six weeks of age with fever of 100.4 degrees F, or higher and no evidence of bacterial infection were seen at the Cincinnati General Hospital from July to December, 1971 . Seventeen of these were admitted to the hospital; 15 were treated with penicillin and kanamycin for possible sepsis . Viral isolation was attempted on 21 of these infants, and ECHO viruses were isolated from 14 (66.7 per cent), compared to three (14.3 per cent) of 21 controls . Eleven of the 14 ECHO viruses isolated were type 4, and the other 3 were types 6, 11, and 25 respectively . Acute and convalescent serum was obtained from 11 of the 21 infants; seven had a fourfold rise in antibody to ECHO virus type 4 . Most of the children had fever with irritability, six of the 23 had a fine maculopapular rash, and three had aseptic meningitis . This study suggests that ECHO viruses may be a significant cause of febrile illness in young infants during the summer and fall and may account for illnesses which lead to hospitalization as possible sepsis.

Ann Thorac Surg, 2002 Jul, 74(1), 185 - 90
Surgical considerations for pulmonary actinomycosis; Endo S et al.; BACKGROUND: Diagnosis and treatment of pulmonary actinomycosis is difficult without surgical intervention . METHODS: Thirteen patients (10 men, 3 women; mean age, 62 years) underwent pulmonary resection and were given a pathologic diagnosis of pulmonary actinomycosis at our institution between 1976 and 2001 . To clarify when pulmonary actinomycosis should be suspected in patients and the role of surgical intervention, we reviewed preoperative clinical characteristics, computed tomography findings, surgical indication, operative procedure, postoperative clinical course, and outcome . RESULTS: Ten patients (77%) had poor oral hygiene . Twelve patients (92%) were symptomatic, and 10 patients (77%) had hemoptysis . The mean interval between radiographic identification of the abnormality and surgical intervention was 8 months (interquartile range, 3.25 to 8 months) . Computed tomography findings in all cases included radiologic opacity with air bronchogram or a low attenuation area . Lung cancer was diagnosed initially because of computed tomography findings of spiculation or pleural indentation, and operation was required in 8 patients (62%) . The others were diagnosed with chronic pneumonia, and surgical intervention became necessary because of recurrent hemoptysis or prolonged illness . Six patients underwent lobectomy; the others underwent partial resection or segmentectomy . Neither complication nor recurrence has occurred . CONCLUSIONS: When patients, particularly those with poor oral hygiene, show radiologic opacity with an air bronchogram or low attenuation area on the computed tomography scan, pulmonary actinomycosis should be considered and penicillin should be administered as diagnostic therapy . Surgical intervention may be necessary when frequent hemoptysis has no resolution or lung neoplasm cannot be ruled out.

Biotechnol Bioeng, 2002 Aug 5, 79(3), 356 - 61
A two-step, one-pot enzymatic synthesis of cephalexin from D-phenylglycine nitrile; Wegman MA et al.; A cascade of two enzymatic transformations is employed in a one-pot synthesis of cephalexin . The nitrile hydratase (from R . rhodochrous MAWE)-catalyzed hydration of D-phenylglycine nitrile to the corresponding amide was combined with the penicillin G acylase (penicillin amidohydrolase, E.C . 3.5.1.11)-catalyzed acylation of 7-ADCA with the in situ-formed amide to afford a two-step, one-pot synthesis of cephalexin . D-Phenylglycine nitrile appeared to have a remarkable selective inhibitory effect on the penicillin G acylase, resulting in a threefold increase in the synthesis/hydrolysis (S/H) ratio . 1,5-Dihydroxynaphthalene, when added to the reaction mixture, cocrystallized with cephalexin . The resulting low cephalexin concentration prevented its chemical as well as enzymatic degradation; cephalexin was obtained at 79% yield with an S/H ratio of 7.7 .

Biotechnol Bioeng, 2002 Jun 5, 78(5), 589 - 93
Penicillin acylase-catalyzed ampicillin synthesis using a pH gradient: a new approach to optimization; Youshko MI et al.; The penicillin acylase-catalyzed synthesis of ampicillin by acyl transfer from D-(-)-phenylglycine amide (D-PGA) to 6-aminopenicillanic acid (6-APA) becomes more effective when a judiciously chosen pH gradient is applied in the course of the process . This reaction concept is based on two experimental observations: 1) The ratio of the initial synthesis and hydrolysis rates (V(S)/V(H)) is pH-dependent and exhibits a maximum at pH 6.5-7.0 for a saturated solution of 6-APA; 2) at a fixed 6-APA concentration below saturation, V(S)/V(H) increases with decreasing pH . Optimum synthetic efficiency could, therefore, be achieved by starting with a concentrated 6-APA solution at pH 7 and gradually decreasing the pH to 6.3 in the course of 6-APA consumption . A conversion of 96% of 6-APA and 71% of D-PGA into ampicillin was accomplished in an optimized procedure, which significantly exceeds the efficiency of enzymatic synthesis performed at a constant pH of either 7.0 or 6.3 .

FEMS Microbiol Lett, 2002 Jul 2, 212(2), 229 - 36
Identification and characterization of the Escherichia coli envC gene encoding a periplasmic coiled-coil protein with putative peptidase activity; Hara H et al.; PM61 is a chain-forming envC strain of Escherichia coli with a leaky outer membrane . It was found to have an oversized penicillin-binding protein 3, which was the result of an IS4 insertion in the prc gene . The other properties of PM61 were caused by the envC mutation . We cloned the envC (yibP) gene and identified the mutation site, causing a single residue substitution, H366Y, in the PM61 envC allele . The gene product was predicted to be a periplasmic protein having coiled-coil structure in the N-terminal region and homology to lysostaphin in the C-terminal region . Overexpression of envC inhibited cell growth, and overexpression of the PM61 mutant allele caused cell lysis . Disruption of the chromosomal envC caused the same defects as the envC point mutation, indicating the gene is dispensable for growth but important for normal septation/separation and cell envelope integrity.

J Pharm Biomed Anal, 2002 Aug 1, 29(6), 1031 - 43
Kinetic analysis of thermal decomposition for penicillin sodium salts: model-fitting and model-free methods; Rodante F et al.; A kinetic study on decomposition processes of some penicillin salts was carried out . Both isothermal and dynamic thermogravimetric curves were used . As expected by their complex structures, several steps with different energies were involved in decomposition processes . Model-fitting and -free kinetic approaches were applied to nonisothermal and isothermal data . The kinetic triplet (f(alpha),A and E(a)) related to model-fitting method that defines a single step reaction resulted to be at variance with the multi-step nature of salts-decomposition . The model-free approach represented by the isothermal and nonisothermal isoconversional methods, gave different dependencies of the activation energy on the extent of conversion . The complex nature of the multi-step process of the studied compounds was more easily revealed using a broader temperature range in nonisothermal isoconversional method . The failure in the model-fitting method did not allow calculating shelf life and half-life times.

Pol Arch Med Wewn, 2002 Feb, 107(2), 161 - 5
{Pulmonary actinomycosis as a complication of foreign body aspiration}; Zielonka TM et al.; This first polish paper presents respiratory actinomycosis as a complication caused by aspiration of a foreign body . Aspiration of a citrus fruit stone occurred as a result of esophagus stenosis and dysphagia caused by a mistake made by a blind person of drinking a caustic substance . Clinical and bronchoscopic features suggested bronchogenic carcinoma but it's not confirmed by two histopathologic examinations of section from pathological bronchial changes . Diagnosis was based on the morphological picture of sections taken during third fibreoptic bronchoscopy and on cytological sputum examination . Removing the aspired foreign body from bronchus and prolonged penicillin treatment resulted in clinical and radiological amelioration.

Sheng Wu Hua Xue Yu Sheng Wu Wu Li Xue Bao (Shanghai), 2000, 32(2), 163 - 168
Increase in Hydrophobicity of Signal Peptide Enhances Secretion of Penicillin G Acylase; Yang YG et al.; An artificial strong hydrophobic signal peptide (ASP), containing ten leucines in tandem in the hydrophobic core, was utilized to replace the wild type signal peptide (WTSP) of penicillin G acylase (PAC), by the fusion to its 4 pro site . PAC expression plasmids, including pKKpacdeltaSP, pKKpacWTSP, pKKpacASP, pETpacWTSP and pETpacASP, were constructed . The length and the amino- and carboxyl-terminus amino acid composition of ASP and WTSP were kept identical . The activity assay and Western-blotting analysis were used to study the effect of ASP and WTSP on the secretion of PAC in tac, T7 and dissolved-oxygen regulation expression systems, respectively . Lack of signal peptide in pKKpacdeltaSP resulted in the accumulation of 91 kD PAC precursor (without signal peptide, but with the space peptide between alpha-subunit and beta-subunit) in the cytosol, indicating that the secretion of PAC depends on the signal peptide . In BL21(pKKpacASP) cells, the PAC activity and proprecursor (with signal peptide and space peptide) processing capacity were increased by about 54% and 38.5%, respectively, in comparison with BL21(pKKpacWTSP) cells . Compared with BL21(DE3) (pETpacWTSP), however, the PAC activity and proprecursor processing capacity in BL21(DE3) (pETpacASP) were enhanced by about 69% and 43.5%, respectively . The PAC activity expressed from pETpacASP was about 67% more than that from pETpacWTSP in the dissolved-oxygen-regulated expression system GJ100 . Resulting from the strong hydrophobicity of ASP, therefore, the PAC activity and proprecursor processing capacity were increased by about 63% and 41% on average, respectively, in comparison with WTSP . In conclusion, the increase in hydrophobicity of the signal peptide hydrophobic core enhanced the secretion of penicillin G acylase.

Drugs, 2002, 62(10), 1447 - 61
Management issues in syphilis; Pao D et al.; Syphilis is a sexually transmitted infection which is systemic from the outset and has increased in incidence worldwide over the last decade . There has been concern as to whether or not co-infection with HIV can modify the clinical presentation of syphilis and, as a genital ulcer disease, it can facilitate the transmission of HIV infection . Diagnosis is based on the microscopic identification of the causative treponeme and serological testing . Recommendations for the treatment of syphilis have been based on expert opinion, case series, some clinical trials and 50 years of clinical experience . Penicillin, given intramuscularly, is the mainstay of treatment and the favoured preparations for early infectious syphilis are benzathine penicillin as a single injection or a course of daily procaine penicillin injections for 10 to 14 days . The duration of treatment is longer for late syphilis . There has been concern that benzathine penicillin may not prevent the development of neurosyphilis but that is a rare outcome with this therapy . The main alternative to penicillin is doxycycline, but the place of azithromycin and ceftriaxone is yet to be established . It is not necessary to carry out examination of the cerebrospinal fluid in patients with early infectious syphilis but it should be performed in those with neurological or ocular signs, psychiatric signs or symptoms, when there is evidence of treatment failure and in those who are co-infected with HIV . Follow-up is an essential part of management and should be particularly assiduous, for at least 24 months, in those co-infected with HIV . Partner notification should be mandatory to try to contain the spread of infection.

Biochem Biophys Res Commun, 2002 Jul 5, 295(1), 55 - 61
C-terminus modification of Streptomyces clavuligerus deacetoxycephalosporin C synthase improves catalysis with an expanded substrate specificity; Chin HS et al.; The biosynthesis of cephalosporins is catalyzed by deacetoxycephalosporin C synthase (DAOCS) . Based on computational, biochemical, and structural analyses, it has been proposed that modification of the C-terminus of DAOCS might be a constructive strategy for engineering improvement in enzyme activity . Therefore, five hydrophilic residues namely N301, Y302, N304, R306, and R307 located in proximity to the C-terminus of Streptomyces clavuligerus DAOCS (scDAOCS) were selected and each substituted with a hydrophobic leucine residue . Substitutions at positions 304, 306, and 307 created mutant scDAOCSs with improved efficiencies in penicillin analog conversion up to 397% . And since it has been previously advocated that the C-terminus is crucial for guiding substrate entry, a truncated mutant DAOCS was constructed to assess its involvement . The truncation of the C-terminus at position 310 in the wild-type scDAOCS resulted in reduction of indiscriminate conversion of penicillin analog but this defect was compensated by the replacement of asparagine with leucine at position 304 . (c) 2002 Elsevier Science (USA).

Biochem J, 2002 Jul 1, 365(Pt 1), 303 - 9
Role of alphaArg145 and betaArg263 in the active site of penicillin acylase of Escherichia coli; Alkema WB et al.; The active site of penicillin acylase of Escherichia coli contains two conserved arginine residues . The function of these arginines, alphaArg145 and betaArg263, was studied by site-directed mutagenesis and kinetic analysis of the mutant enzymes . The mutants alphaArg145-->Leu (alphaArg145Leu), alphaArg145Cys and alphaArg145Lys were normally processed and exported to the periplasm, whereas expression of the mutants betaArg263Leu, betaArg263Asn and betaArg263Lys yielded large amounts of precursor protein in the periplasm, indicating that betaArg263 is crucial for efficient processing of the enzyme . Either modification of both arginine residues by 2,3-butanedione or replacement by site-directed mutagenesis yielded enzymes with a decreased specificity (kcat/K(m)) for 2-nitro-5-{(phenylacetyl)amino}benzoic acid, indicating that both residues are important in catalysis . Compared with the wild type, the alphaArg145 mutants exhibited a 3-6-fold-increased preference for 6-aminopenicillanic acid as the deacylating nucleophile compared with water . Analysis of the steady-state parameters of these mutants for the hydrolysis of penicillin G and phenylacetamide indicated that destabilization of the Michaelis-Menten complex accounts for the improved activity with beta-lactam substrates . Analysis of pH-activity profiles of wild-type enzyme and the betaArg263Lys mutant showed that betaArg263 has to be positively charged for catalysis, but is not involved in substrate binding . The results provide an insight into the catalytic mechanism of penicillin acylase, in which alphaArg145 is involved in binding of beta-lactam substrates and betaArg263 is important both for stabilizing the transition state in the reaction and for correct processing of the precursor protein.

Minerva Pediatr, 2002 Jun, 54(3), 243 - 7
{Loeffler syndrome and Mycoplasma pneumonitis . A case report}; Celandroni A et al.; We describe a clinical case of Loeffler syndrome occurred in a famale aged 13 years . This syndrome is characterized by fleeting pulmonary infiltrates and blood eosinophilia until 70% . Patients usually are only mildly ill or asymptomatic and recovery occurs from few days to some months . Principle causes are: a) mycetes as Aspergillus; b) helmints as Toxocara, Ancylostoma, Trichinella, Ascaris, Strongyloides, Schistosoma; c) chemical agents such as penicillin, para-aminosalycilic acid, hydralazine, nitrofurantoine, chlorpropamide . This girl came to our observation in good general conditions with murmur reduction on the thorax left side, marked peripheral eosinophilia (E 55% of 6100 white blood cell), right pulmonary infiltrate on RX and CT scan . One month before she had fever, treated with amoxycillin and clavulanic acid . Mantoux, Prick tests for main inhalant allergenes, ACE, repeated stools and seric investigations for parasites, mycetes and organisms, were negative except for IgM anti-Myco-plasma antibodies . Broncholavage showed marked eosinophilia . Smear didn't show any blast . The girl recovered in about 40 days (E 4.1% of 8500 WBC, RX negative) . Our hypotesis is a causative role of amoxycillin in inducing the syndrome, even if this is a rare event, with an overlapping of a Mycoplasma infection.

Scand J Infect Dis, 2002, 34(4), 257 - 61
Treatment of latent syphilis in HIV-infected patients with 10 d of benzylpenicillin G benethamine: a prospective study in Maputo, Mozambique; Tattevin P et al.; Neurosyphilis has been reported in HIV-infected patients previously treated with penicillin G benzathine, which does not achieve treponemicidal levels in cerebrospinal fluid . Therapy combining benzylpenicillin G and its repository form benzylpenicillin G benethamine could be a potentially effective alternative enhanced regimen for treating latent syphilis in HIV-infected patients because peak serum and cerebrospinal fluid concentrations would be achieved early post-administration by the former molecule and sustained for 24 h due to the prolonged half-life of the latter . In this study, 23 asymptomatic HIV and Treponema pallidum co-infected patients received 10 d of combined therapy (2 M IU intramuscular once daily) and were followed up at 3, 6 and 12 months . None experienced side effects or clinical symptoms . Of the 18 patients who were evaluated 1 y later, 8 (44.4%) exhibited serological treatment failure, defined as a positive serum rapid plasma reagin test . In conclusion, a 10-d regimen combining penicillin G and penicillin G benethamine seems to be of no benefit compared to currently recommended treatment.

J Pharm Biomed Anal, 2002 Jul 1, 29(3), 569 - 78
Monitoring of enzymatic hydrolysis of penicillin G by pyrolysis-negative ion mass spectrometry; Ghassempour A et al.; A pyrolysis-negative ion mass spectrometry (Pyr-NIMS) is used for the monitoring of enzymatic hydrolysis of penicillin G (Pen G) to 6-aminopenicillanic acid (6-APA) and phenyl acetic acid (PAA) . The high sensitivity and rapid response time of Pyr-NIMS allow its application to the simultaneously determination of these compounds . The mass to charge (m/z) values of 262, 156 and 135 of Pen G, 6-APA and PAA respectively, are used for the quantitative measurements by selected ion monitoring (SIM) . The limit of detection (LOD), linearity and relative standard deviation (n=5) are 10 ng ml(-1), 100 ng ml(-1)-1000 mg ml(-1) and 1.5%, respectively The results are compared with high performance liquid chromatography (HPLC) . An important advantage of the presented analytical system is the high linearity of signals without preliminary separation and recalibration . The main and interactive effects of pH, temperature and concentration of Pen G for enzymatic hydrolysis of Pen G are studied . Optimize conditions of pH (8), temperature (28 degrees C) and concentration of Pen G (12% w/v) in real samples are obtained.

J Inorg Biochem, 2002 Apr 28, 89(3-4), 279 - 92
Organometallic complexes with biological molecules . XVII . Triorganotin(IV) complexes with amoxicillin and ampicillin; Di Stefano R et al.; Novel triorganotin(IV) complexes of two beta-lactamic antibiotics, 6-{D-(-)-beta-amino-p-hydroxyphenyl-acetamido}penicillin (=amoxicillin) and 6-{D-(-)-alpha-aminobenzyl}penicillin (=ampicillin), have been synthesized and investigated both in solid and solution states . The complexes corresponded to the general formula R(3)Sn(IV)antib*H(2)O (R=Me, n-Bu, Ph; antib=amox=amoxicillinate or amp=ampicillinate) . Structural investigations about configuration in the solid state have been carried out by interpreting experimental IR and 119Sn Mossbauer data . In particular, IR results suggested polymeric structures both for R(3)Sn(IV)amox.H(2)O and R(3)Sn(IV)amp*H(2)O . Moreover, both antibiotics appear to behave as monoanionic bidentate ligands coordinating the tin(IV) atom through ester-type carboxylate, as well as through the beta-lactamic carbonyl . Evidence that in none of these compounds water molecules were involved in coordination, was provided by thermogravimetric investigations . On the basis of 119Sn Mossbauer spectroscopy it can be inferred that tin(IV) was pentacoordinate in all of the complexes in the solid state, showing an equatorial R(3)Sn(IV) trigonal bipyramidal (tbp) configuration . The nature of the complexes in solution state was investigated by using 1H and 13C nuclear magnetic resonance (NMR) spectroscopy, while an 119Sn spectrum was obtained for n-Bu(3)Sn(IV)amp*H(2)O . Although 1H- and 13C-NMR measurements suggested that in dimethyl sulfoxide (DMSO)-d(6) solution the polymeric structure collapsed, due to a solvolysis process of the beta-lactamic carbonyl bonding to the organometallic moiety, the complexes have been shown to maintain the same trigonal bipyramidal configuration at tin(IV) atom by the coordination of a DMSO molecule . Cytotoxic activity of these novel semisynthetic antibiotic derivatives has been tested towards spermatocyte chromosomes of the mussel Brachidontes pharaonis (Mollusca: Bivalvia) using two different chromosome-staining techniques such as Giemsa and CMA(3) . The occurrence of typical colchicinized-like (c-like) mitoses on slides obtained from animals exposed to organotin compounds, directly confirmed the high mitotic spindle-inhibiting potency of these chemicals . In addition, by comparative analysis of spermatocyte chromosomes from untreated specimens (negative controls) and specimens treated with the triorganotin(IV) complexes, structural damages such as 'achromatic lesions' and 'chromosome breakages' have been identified.

Mediators Inflamm, 2002 Apr, 11(2), 105 - 11
Cytokine secretion by decidual lymphocytes in transient hypertension of pregnancy and pre-eclampsia; Wilczynski JR et al.; BACKGROUND: Transient hypertension (TH) and preeclampsia (PE) are believed to have different pathophysiology . However, 15-25% of pregnant women initially diagnosed as having TH develop PE . To clarify the immuno-pathogenetical connections between the two syndromes, we studied the pattern of T helper cell (Th)1/Th2 cytokine balance disturbances existing inside maternal decidua in normal pregnancy (NP) and pregnancies complicated with TH and PE . METHODS: Third-trimester decidual tissue was obtained by curettage of uterine cavity during elective caesarean sections in NP (n = 11), TH (n = 17) and PE (n = 21) patients . Cell suspensions were prepared by an electromechanical dispersal method and centrifugated using a standard gradient sedimentation technique . Isolated lymphocytes were placed in medium (RPMI 1640, 10% fetal calf serum, L-glutamine, penicillin, streptomycin) and cultured for 72 h with or without mitogen phytohaemaglutinine (PHA) . The enzyme-linked immunosorbent assay method was used for estimation of interleukin (IL)-2, IL-4, IL-6, IL-10, IL-12 and interferon-gamma (IFN-gamma) in culture supernatant . STATISTICAL ANALYSIS: The Kruskal-Wallis and the Mann-Whitney U tests were used (p < 0.05) . RESULTS: Both spontaneous and PHA-stimulated secretion of Th2-type cytokines IL-6 and IL-10 was decreased in PE patients compared with TH and NP patients . The concentration of Th1-type cytokine IFN-gamma was increased in patients suffering both from TH and PE . CONCLUSION: On the base of decidual cytokine secretion, both PE and TH are syndromes of local Th1/Th2 cytokine balance disturbances as compared with NP, and TH seems to be an intermediate step to PE.

Folia Microbiol (Praha), 2002, 47(2), 189 - 92
Evaluation of strains derived from Escherichia coli W as hosts for the expression of penicillin G-acylase-encoding gene cloned on the recombinant plasmid pKA18; Grafkova J et al.; The potential for production of penicillin G-acylase (PGA), encoded by the chromosomal gene pgai, of four strains belonging to a genealogical line derived from the strain Escherichia coli W, was evaluated in a medium with and without the inducer phenylacetic acid (PA) . These strains were used as hosts of the recombinant plasmid pKA18, in which the structural gene pgac isolated from the strain RE3, the best host strain of a line giving the highest production, was cloned . The presence of the inducer reduced the copy number of the plasmid in all recombinant strains . Only in recombinant strain RE3 (pKA18) the reduction of the gene dosage of pgac resulted also in the reduction of the amount of PGA synthesized by the cells . The reduced activity of the cells did not result from a segregation of plasmid-free clones . Also the growth rate was decreased by 20 and 40% in the host and recombinant strains, respectively . The host strain RE3 showing the highest production of PGA was also the best host of the recombinant plasmid in terms of the segregational stability and copy number (198 copies per chromosome) . The recombinant strain RE3 (pKA18) also provided the highest production of PGA.

J Bacteriol, 2002 Jul, 184(13), 3749 - 52
Penicillin-binding proteins 1a and 1b form independent dimers in Escherichia coli; Charpentier X et al.; We report here that PBP1a can dimerize but does not interact with PBP1b to form PBP1a/PBP1b heterodimers in Escherichia coli . These findings support the idea of a relevant involvement of dimerization of both PBP1a and PBP1b during murein synthesis and suggest the existence of different peptidoglycan synthesis complexes.

J Bacteriol, 2002 Jul, 184(13), 3630 - 9
Contribution of membrane-binding and enzymatic domains of penicillin binding protein 5 to maintenance of uniform cellular morphology of Escherichia coli; Nelson DE et al.; Four low-molecular-weight penicillin binding proteins (LMW PBPs) of Escherichia coli are closely related and have similar DD-carboxypeptidase activities (PBPs 4, 5, and 6 and DacD) . However, only one, PBP 5, has a demonstrated physiological function . In its absence, certain mutants of E . coli have altered diameters and lose their uniform outer contour, resulting in morphologically aberrant cells . To determine what differentiates the activities of these LMW PBPs, we constructed fusion proteins combining portions of PBP 5 with fragments of other DD-carboxypeptidases to see which hybrids restored normal morphology to a strain lacking PBP 5 . Functional complementation occurred when truncated PBP 5 was combined with the terminal membrane anchor sequences of PBP 6 or DacD . However, complementation was not restored by the putative carboxy-terminal anchor of PBP 4 or by a transmembrane region of the osmosensor protein ProW, even though these hybrids were membrane bound . Site-directed mutagenesis of the carboxy terminus of PBP 5 indicated that complementation required a generalized amphipathic membrane anchor but that no specific residues in this region seemed to be required . A functional fusion protein was produced by combining the N-terminal enzymatic domain of PBP 5 with the C-terminal beta-sheet domain of PBP 6 . In contrast, the opposite hybrid of PBP 6 to PBP 5 was not functional . The results suggest that the mode of PBP 5 membrane anchoring is important, that the mechanism entails more than a simple mechanical tethering of the enzyme to the outer face of the inner membrane, and that the physiological differences among the LMW PBPs arise from structural differences in the DD-carboxypeptidase enzymatic core.

Ann Dermatol Venereol, 2002 Apr, 129(4 Pt 1), 375 - 9
{Hospitalization criteria for erysipelas: prospective study in 145 cases}; Jegou J et al.; INTRODUCTION: Two recent studies conducted in France among general practitioners have shown that they only hospitalized between 20 to 50 percent of patients with erysipelas seen in private practice . We therefore conducted a hospital-based, prospective study designed to determine the hospitalization criteria for erysipelas, since a number of patients are also hospitalized directly through the emergency department . PATIENTS AND METHODS: This prospective, hospital-based study, included patients hospitalized for clinical diagnosis of erysipelas in 9 centres in north-eastern France . Clinical data were recorded using a standard questionnaire filled-in during the first 72 hours of hospitalization . They included: demographic (name and first name initials, age, sex) and clinical (location of erysipelas) characteristics, as well as the origin of the patient (home, emergency department, other department), the reasons for hospitalization (severity of local or systemic signs, suspicion of deep vein thrombosis, location on the face, age over 60 years, associated diseases, absence of improvement after ambulatory treatment, socioeconomic reasons or on principle hospitalization) . Patients hospitalized by (or without) a general practitioner were compared using Chi-2 and Student t tests . RESULTS: One hundred forty-five adults (80 women and 65 men; mean age 61 +/- 20 years) were included in the study: 89 patients (61 p . 100) were hospitalized by a general practitioner whereas 56 (39 percent) went directly to the emergency department . In 128/145 cases (88 p . 100), erysipelas was localized on the lower limbs . The mean number of reasons for hospitalization per patient was of 2.2 +/- 1.2 . The most frequent reason for hospitalization was an associated disease (diabetes, obesity, alcoholism, immunodeficiency), present in 77 cases (53 p . 100) . Patients hospitalized through a general practitioner were older than those hospitalized directly through the emergency department (68 vs 51 years; p<0.001) . Patients hospitalized by a general practitioner more frequently had an erysipelas located on the lower limbs (94 p . 100 vs 79 p . 100; p<0.001) and the mean number of reasons for hospitalization was greater (2.4 vs 1.7; p<0.001), especially suspicion of deep vein thrombosis and elevated mean age . The treatment started during hospitalization was intravenous penicillin G in 67 cases (46 p . 100), oral pristinamycin in 28 cases (19 p . 100) and intravenous or oral amoxicillin in 9 cases (6 p . 100) . COMMENTS: This study demonstrates the existence of two distinct courses of hospitalization for erysipelas . Patients hospitalized by a general practitioner were older and their erysipelas more frequently located on the lower limbs and deep vein thrombosis was suspected . Our study also shows the emergence of a population of patients younger and without medical supervision, for whom the general practitioner is replaced by the emergency department of the local hospital . Nevertheless, the most frequent reason for hospitalization in both groups is the existence of an associated disease, possibly responsible for further complications.

Evol Dev, 2002 May-Jun, 4(3), 212 - 22
Ontogenetic torsion in two basal gastropods occurs without shell attachments for larval retractor muscles; Page LR; Results of this study on two species of vetigastropods contradict the long-standing hypothesis, originally proposed by Garstang (1929), that the larval retractor muscles power the morphogenetic movement of ontogenetic torsion in all basal gastropods . In the trochid Calliostoma ligatum and the keyhole limpet Diodora aspera, the main and accessory larval retractor muscles failed to establish attachments onto the protoconch (larval shell) when the antibiotics streptomycin sulfate and penicillin G were added to cultures soon after fertilization . Defects in protoconch mineralization were also observed . Despite these abnormalities, developing larvae of these species accomplished complete or almost complete ontogenetic torsion, a process in which the head and foot rotate by 180 degrees relative to the protoconch and visceral mass . Analysis by using phalloidin-fluorophore conjugate and transmission electron microscopy showed that myofilaments differentiated within myocytes of the larval retractor muscles and adherens-like junctions formed between muscle and mantle epithelial cells in both normal and abnormal larvae . However, in abnormal larvae, apical microvilli of mantle cells that were connected to the base of the larval retractor muscles failed to associate with an extracellular matrix that normally anchors the microvilli to the mineralized protoconch . If morphogenesis among extant, basal gastropods preserves the original developmental alteration that created gastropod torsion, as proposed by Garstang (1929), then the alteration involved something other than the larval retractor muscles . Alternatively, the developmental process of torsion has evolved subsequent to its origin in at least some basal gastropod clades so that the original alteration is no longer preserved in these clades.

Pol Merkuriusz Lek, 2002 Mar, 12(69), 194 - 7
{Value of the leukotriene generation test in diagnosis of immediate hypersensitivity to penicillin}; Medrala W et al.; In this study we have decided to explore the diagnostic usefulness of CAST-ELISA test in patients with immediate allergic reactions caused by penicillin . Peripheral blood leukocytes were stimulated by commercially available penicillin allergens--Penicillin G, Benzyl-penicillin--Polylysine and specially performed Penicillin G conjugated to human serum albumin . Test was performed in 33 allergic persons and in 13 control healthy persons well tolerated penicillin antibiotics with negative skin tests results . CAST-ELISA test gave the positive results in 30.3% when unconjugated penicillin was used and in 18.18% with penicillin--polylysine . The best results were obtained when cells were stimulated with penicillin conjugated to human serum albumin--positive results were observed in 47.82% . Accumulate percentage of positive results was 73.91% . In our opinion CAST-ELISA test is reliable method in diagnosis of immediate allergic reactions caused by penicillin and inclusion of penicillin conjugated to human serum albumin seems to be justifiable.

Pediatr Neurosurg, 2002 May, 36(5), 236 - 43
Ninth cranial nerve stimulation for epilepsy control . Part 1: efficacy in an animal model; Patwardhan RV et al.; OBJECTIVE: To characterize the effects of stimulation of the nerve of Hering (HN; cranial nerve nine) in controlling seizure activity using a canine model . METHODS: Using penicillin applied topically to a region of the cerebral cortex, 16 seizure-type continuous epileptiform discharges were generated . Ten specimens of HN (five left-sided and five right-sided) were dissected from the cervical region in five dogs and stimulated at varying parameters to determine the effects in controlling epileptiform activity . Electroencephalography (using a multielectrode array), electrocardiography and other vital signs were continuously monitored for side effects . RESULTS: Resolution of continuous epileptiform activity following stimulation was found in 12 of 16 trials (75%); no spontaneous resolution was noted in the absence of stimulation, and stimulation significantly shortened seizure duration (p < 0.05) . Mean epileptiform activity duration was 139 s prior to stimulation (range 1-432 s), with a mean poststimulation delay of 17 s until resolution and a mean interictal time of 399 s . Two specimens became free of seizure activity for the duration of our study (p < 0.001) . No significant side effects (such as the potentially life-threatening cardiac problems seen with right-sided cervical vagal nerve stimulation) were found with stimulation of either left- or right-sided HN . Stimulation of other regional nerves (e.g . twelfth cranial nerve, nerves of the cervical plexus) failed to yield similar control of epileptiform activity . CONCLUSIONS: The results of this pilot study suggest that stimulation of the HN can successfully control focal seizure activity in the majority of cases . Pending further study, stimulation of the HN may have a role in the management of patients suffering from medically and otherwise surgically refractory epilepsy .

Pharmacoeconomics, 2002, 20(6), 357 - 66
Sickle cell anaemia: epidemiology and cost of illness; Nietert PJ et al.; The purpose of this paper was to review the research examining the epidemiology of and costs associated with sickle cell anaemia (SCA) . Although there is general acceptance that Black populations are at greatest risk of the disease, estimates of disease incidence and prevalence vary greatly among different Black populations . In addition, the sickle cell haemoglobinopathy poses a health problem to many other ethnic groups, including populations native to Italy, Greece, Turkey, Saudi Arabia, India, Pakistan, Bangladesh, China, and Cyprus . As penicillin prophylaxis has been shown to reduce the risk of sepsis among children with SCA, many governments have established newborn screening programmes to improve the health outcomes for patients with this disease . As a group, patients with SCA incur large numbers of hospital admissions, emergency department visits, and outpatient visits, often at substantial costs, hence, obtaining adequate health insurance is a problem for many patients . A common theme present in studies reviewed in this article is that a small proportion of patients tends to account for a majority of the total healthcare costs . As new diagnostic methods and treatment options become available, balancing costs associated with SCA and quality of healthcare will continue to present challenges to many healthcare providers and insurers.

Biotechnol Prog, 2002 May-Jun, 18(3), 629 - 34
Epoxy sepabeads: a novel epoxy support for stabilization of industrial enzymes via very intense multipoint covalent attachment; Mateo C et al.; Sepabeads-EP (a new epoxy support) has been utilized to immobilize-stabilize the enzyme penicillin G acylase (PGA) via multipoint covalent attachment . These supports are very robust and suitable for industrial purposes . Also, the internal geometry of the support is composed by cylindrical pores surrounded by the convex surfaces (this offers a good geometrical congruence for reaction with the enzyme), and it has a very high superficial density of epoxy groups (around 100 micromol/mL) . These features should permit a very intense enzyme-support interaction . However, the final stability of the immobilized enzyme is strictly dependent on the immobilization protocol . By using conventional immobilization protocols (neutral pH values, nonblockage of the support) the stability of the immobilized enzyme was quite similar to that achieved using Eupergit C to immobilize the PGA . However, when using a more sophisticated three-step immobilization/stabilization/blockage procedure, the Sepabeads derivative was hundreds-fold more stable than Eupergit C derivatives . The protocol used was as follows: (i) the enzyme was first covalently immobilized under very mild experimental conditions (e.g., pH 7.0 and 20 degrees C); (ii) the already immobilized enzyme was further incubated under more drastic conditions (higher pH values, long incubation periods, etc.) in order to "facilitate" the formation of new covalent linkages between the immobilized enzyme molecule and the support; (iii) the remaining epoxy groups of the support were blocked with very hydrophilic compounds to stop any additional interaction between the enzyme and the support . This third point was found to be critical for obtaining very stable enzymes: derivatives blocked with mercaptoethanol were much less stable than derivatives blocked with glycine or other amino acids . This was attributed to the better masking of the hydrophobicity of the support by the amino acids (having two charges).

Biotechnol Prog, 2002 May-Jun, 18(3), 483 - 8
Penicillin G acylase-fatty lipid biocomposite films show excellent catalytic activity and long term stability/reusability; Phadtare S et al.; The formation of biocomposite films of the pharmaceutically important enzyme penicillin G acylase (PGA) and fatty lipids under enzyme-friendly conditions is described . The approach involves a simple beaker-based diffusion protocol wherein the enzyme diffuses into the lipid film during immersion in the enzyme solution, thereby leading to the formation of a biocomposite film . The incorporation of the enzyme in both cationic as well as anionic lipids suggests the important role of secondary interactions such as hydrophobic and hydrogen bonding in the enzyme immobilization process . The kinetics of formation of the enzyme-lipid biocomposites has been studied by quartz crystal microgravimentry (QCM) measurements . The stability of the enzyme in the lipid matrix was confirmed by Fourier transform infrared spectroscopy (FTIR) and biocatalytic activity measurements . Whereas the biological activity of the lipid-immobilized enzyme was marginally higher than that of the free enzyme, the biocomposite film exhibited increased thermal/temporal stability . Particularly exciting was the observation that the biocomposite films could be reused in biocatalysis reactions without significant loss in activity, which indicates potentially exciting biomedical/industrial application of these films.

Eur J Biochem, 2002 Jun, 269(11), 2735 - 9
The role of arginine residues in substrate binding and catalysis by deacetoxycephalosporin C synthase; Lipscomb SJ et al.; Deacetoxycephalosporin C synthase (DAOCS) catalyses the oxidative ring expansion of penicillin N, the committed step in the biosynthesis of cephamycin C by Streptomyces clavuligerus . Site-directed mutagenesis was used to investigate the seven Arg residues for activity (74, 75, 160, 162, 266, 306 and 307), selected on the basis of the DAOCS crystal structure . Greater than 95% of activity was lost upon mutation of Arg-160 and Arg266 to glutamine or other residues . These results are consistent with the proposed roles for these residues in binding the carboxylate linked to the nucleus of penicillin N (Arg160 and Arg162) and the carboxylate of the alpha-aminoadipoyl side-chain (Arg266) . The results for mutation of Arg74 and Arg75 indicate that these residues play a less important role in catalysis/binding . Together with previous work, the mutation results for Arg306 and Arg307 indicate that modification of the C-terminus may be profitable with respect to altering the penicillin side-chain selectivity of DAOCS.

Biochim Biophys Acta, 2002 Jun 3, 1597(2), 292 - 300
pH, inhibitor, and substrate specificity studies on Escherichia coli penicillin-binding protein 5; Stefanova ME et al.; The recent structural determination of Escherichia coli penicillin-binding protein 5 (PBP 5) provides the opportunity for detailed structure-function studies of this enzyme . PBP 5 was investigated in terms of its stability, linear reaction kinetics, acyl-donor substrate specificity, inhibition by a number of active site-directed reagents, and pH profile . PBP 5 demonstrated linear reaction kinetics for up to several hours . Dilution of PBP 5 generally resulted in substantial loss of activity, unless BSA or a BSA derivative was added to the diluting buffer . PBP 5 did not demonstrate a significant preference against a simple set of five alpha- and epsilon-substituted L-Lys-D-Ala-D-Ala derivatives, suggesting that PBP 5 lacks specificity for the cross-linked state of cell wall substrates . Among a number of active site-directed reagents, only some thiol-directed reagents gave substantial inhibition . Notably, serine-directed reagents, organic phosphates, and simple boronic acids were ineffective as inhibitors . PBP 5 was stable over the pH range 4.6-12.3, and the k(cat)/K(m) vs . pH profile for activity against Ac(2)-L-Lys-D-Ala-D-Ala was bell-shaped, with pK(a)s at 8.2 and 11.1 . This is the first complete pH profile, including both acidic and basic limbs, for a PBP-catalyzed DD-carboxypeptidase (CPase) reaction . Based on its structure, similarity to Class A beta-lactamases, and results from mutagenesis studies, the acidic and basic limbs of the pH profile of PBP 5 are assigned to Lys-47 and Lys-213, respectively . This assignment supports a role for Lys-47 as the general base for acylation and deacylation reactions.

Wiad Lek, 2002, 55(1-2), 81 - 7
{Difficulties with using T lymphocyte culture as a method for diagnosing allergies to benzylpenicillin}; Zdziarski P; The activation of T lymphocytes upon antigen stimulation plays a crucial role in adverse immune responses including drug-specific hypersensitivity reactions . The helpfulness of conventional tritiated thymidine incorporation assay for penicillin allergy diagnostics is limited . Benzylpenicillin, as a reactive compound, constitutes typical example of hapten . Most of research on penicillin hypersensitivity use benzylpenicillin-albumin (BPO-HSA) conjugates . Thus in this study we describe an in vitro proliferation assay with benzylpenicillin or penicillin and autologous serum protein conjugates . Interestingly these conjugates enhanced incorporation of tritiated thymidyne, when benzylpenicillin did not exert an influence on PBMCs proliferation (correlation coefficient r = -0.0119) . This so-called carrier-effect indicates that benzylpenicillin and serum globulin complexes can take part in penicillin allergy (primary immune response) . Optimal secondary response is obtained when the benzylpenicillin bind the same carrier for both primary and secondary immunization . Father-proliferation assay with modification of responses to phytohaemagglutinin by benzylpenicilloilated serum protein results in significant decrease of incorporation of {3H} thymidyne . Otherwise benzylpenicillin did not modify postmitogenic proliferation of PBMCs . Our findings indicate that the use of penicillin and autologous serum protein conjugates is helpful . This study show the manner in which benzylpenicillin forms T-cell epitopes.

Sheng Wu Hua Xue Yu Sheng Wu Wu Li Xue Bao (Shanghai), 2001, 33(4), 437 - 442
Inhibitive Effect of N-nitro-L-arginine on Hippocampal Neurons Excitation; Chen XC et al.; The inhibitive effect of N-nitro-L-arginine (L-NNA, a nitric oxide synthase inhibitor) on the excitation of cultured rat hippocampal CA1 neurons, stimulated by penicillin G(PG), was investigated . A rapid intracellular NO production induced by PG (4 000 IU/ml) was disclosed when monitored with laser scanningconfocal microscopy (LSCM) . Pretreatment of L-NNA (0--10 &mgr;mol/L) dose-dependently inhibited the NO production, and the intercellular level of glutamate (15 min after PG stimulation) as well . Meanwhile, L-NNA(1 and 10 &mgr;mol/L) also significantly inhibited the immunoreactive methionine enkephalin (ir-M-ENK) level . Furthermore, the immunoreactive dynorphin B (ir-DYN-B) level was increased significantly by L-NNA (10 &mgr;mol/L) . Finally, beta-FNA (100 &mgr;mol/L, an M-ENK receptor inhibitor) facilitated the inhibitive effect of L-NNA on the Glu level, while nor-BIN (100 &mgr;mol/L, a DYN receptor inhibitor) suppressed that effect . In conclusion,L-NNA could inhibit NO production induced by PG (4 000 IU/ml) stimulation, thuslowering the M-ENK level and increasing the DYN-B level, and resulted in a down-regulation of the Glu level and the neuron excitation.

Sheng Wu Hua Xue Yu Sheng Wu Wu Li Xue Bao (Shanghai), 2001, 33(6), 671 - 676
Mutagenesis of N-terminal Amino Acid Residues in beta-subunit of Glutaryl-7-amino-cephalosporanic Acid Acylase C130; Zhang N et al.; In many GL-7ACA acylases, the first Ser residue at the N-terminal of beta-subunit is the catalytic center . In order to investigate relationship between the N-terminal structure and catalytic activities, peptide replacement and site-directed mutagenesis were performed at the N-terminal of beta-subunit of GL-7ACA acylase C130 . When the N-terminal 8 amino acid residues of C130 were replaced by the corresponding sequence of penicillin acylases PAC and PGA, respectively, the first mutant B8PAC lost the activity of the acylase, and the second mutant B8PGA had lower activity with the K(m) value increasing from 0.44x10(-3)mol.L(-1) to 0.55x10(-3) mol.L(-1), and the k(cat) decreasing from 4.92 s(-1) to 1.64 s(-1) . Although the substitution of Trp (beta4) by Tyr did not change the K(m) value, the k (cat) decreased to 2.29 s(-1) . When the Trp was substitued by Leu, both the K ( m ) and k ( cat ) values decreased . Compared with the wild type, mutations of Ser (beta3) to Met, Ala and Cys caused decrease of K(m) values by 52.27%, 43.18% and 38.64%, respectively . Mutation of Asn (beta2) to Gln caused the K ( m ) value being increased by 5-fold, and k ( cat ) decreased by 10-fold . These results suggested that the N-terminal amino acid residues of beta-subunit in GL-7ACA acylase C130 are important for enzyme function.

Lett Appl Microbiol, 2002, 34(6), 413 - 6
Enzymes for animal feeding from Penicillium chrysogenum mycelial wastes from penicillin manufacture; Nuero OM et al.; AIMS: Several enzymes from mycelial wastes of Penicillium chrysogenum fungal cultures from penicillin manufacture were studied as supplements for animal feeding . METHODS AND RESULTS: Proteins were precipitated with tannic acid, acetone, ethanol or polyethyleneglycol 6000 . The levels of the enzyme activities found in the different precipitates were similar . The activities of invertase, beta-1,3-glucanase, lipase and tannase were higher and those of amylase, cellulase, pectinase, protease and xylanase were lower . Precipitation with tannic acid was selected as an easy and simple method . CONCLUSIONS, SIGNIFICANCE AND IMPACT OF THE STUDY: An enzymatic precipitate from these P . chrysogenum wastes, comparable to a commercial enzymatic additive used in animal feeding, was obtained.

BMC Genet . 2002 Apr 25;3(1):6.
Occurrence of leu+ revertants under starvation cultures in Escherichia coli is growth-dependent; Jin J et al.; BACKGROUND: Many investigations have reported that advantageous mutations occurred more frequently under selective conditions than those under non-selective conditions . This phenomenon is referred to as adaptive mutation . Their characteristics are that adaptive mutations are directed and growth-independent . The idea of directed adaptive mutation had been objected by some reports, however, the idea of growth-independent adaptive mutation has been held till today . RESULTS: In this paper, we have observed that under leucine starvation conditions, leu+ revertants accumulated as a function of time; leu- to leu+ reverse mutation rates and frequencies were higher than those under non starvation conditions; and no divided cells could be monitored by the penicillin method . These results were similar to the time-dependent manner of adaptive mutation from previous reports . However, leucine concentration determinate experiments revealed that certain traces of leucine, which leaked from the E . coli cells, was almost always present in the culture . More numbers of leu+ revertants appeared when the similar cultures were dropped in small areas on the selective plates than when spread on the whole selective plates . These results have shown that mutations under leucine starving conditions are growth-dependent . Fluctuation analysis of leu+ revertants indicated that leu-leu+ mutation occurred spontaneously and randomly . In addition, the spectra of leuB gene in the revertants proved that mutations under selective conditions were not specific or directed . CONCLUSIONS: The above investigations led to the conclusion (1) that the occurrence of leu+ mutations under starvation conditions was growth-dependent . The occurrence mutations was also similar to that under non-starvation conditions (2) . Under starvation conditions the mutation rates were higher, and was not constant during the long process.

Biochim Biophys Acta, 2002 Apr 3, 1589(2), 104 - 11
Assessment of the microbody luminal pH in the filamentous fungus Penicillium chrysogenum; van der Lende TR et al.; The enzymes of the penicillin biosynthetic pathway in Penicillium chrysogenum are located in different subcellular compartments . Consequently, penicillin pathway precursors and the biologically active penicillins have to cross one or more membranes . The final enzymatic step that is mediated by acyltransferase takes place in a microbody . The pH of the microbody lumen in penicillin producing cells has been determined with fluorescent probes and mutants of the green fluorescent protein and found to be slightly alkaline.

Chemistry, 2002 Apr 15, 8(8), 1879 - 87
Synthesis of nucleopeptides by employing an enzyme-labile urethane protecting group; Jeyaraj DA et al.; Nucleoproteins are naturally occurring biopolymers in which the hydroxy group of a serine, a threonine, or a tyrosine moiety is linked through a phosphodiester group to the 3'- or 5'-end of a nucleic acid . For the study of the biological phenomena in which nucleoproteins are involved, for example, viral replication, nucleopeptides embodying the characteristic linkage between the peptide chain and the oligonucleotide may serve as powerful tools . However, as a result of the multifunctionality and the pronounced acid and base lability of nucleopeptides, their synthesis requires the application of a variety of orthogonally stable blocking groups, which can be removed under the mildest conditions . We have developed a new mild enzymatic deprotection method, that is, the penicillin G acylase-catalyzed hydrolysis of the N-phenylacetoxybenzyloxycarbony (PhAcOZ) group, for the synthesis of nucleopeptides . We demonstrate the wide applicability of this method by coupling the N-terminally deprotected nucleopeptides 31 a-c with PhAcOZ-protected amino acids and subsequent removal of the N-PhAcOZ group from fully protected nucleotetrapeptides 32 a,b with penicillin G acylase . The reaction conditions are very mild (pH 6.8) so that no undesired side reaction such as cleavage of the nucleotide bond or beta-elimination of the nucleotide was observed.

Scand J Urol Nephrol, 2002 Feb, 36(1), 87 - 8
Ureteric obstruction caused by pelvic actinomycosis; Ord J et al.; Ureteric obstruction is a well-known complication of actinomycosis, however its management in previous case reports has been very variable and sometimes mutilating . We report a rare case presenting with ischiorectal abscess that was successfully treated by JJ stenting and penicillin.

J Pharm Pharmacol, 2002 Apr, 54(4), 499 - 508
The influence of caprate on rectal absorption of phenoxymethylpenicillin: experience from an in-vivo perfusion in humans; Lennernas H et al.; The aim of this in-vivo perfusion study in humans was to investigate the influence of a penetration enhancer, sodium caprate, on the rectal absorption of phenoxymethylpenicillin and antipyrine . Six subjects, 3 male and 3 female, were included in two separate studies using perfusion solution of different pH (T1 and T2, respectively) . Each in-vivo rectal perfusion investigation lasted for 200 min and consisted of two periods of 100 min, the first serving as a control, and sodium caprate being added in the second period in both T1 and T2 . The concentrations of phenoxymethylpenicillin, antipyrine and sodium caprate in the outlet perfusate were assayed by HPLC, as was the plasma concentrations of phenoxymethylpenicillin . At pH 6.0 (0-100 min) the fraction absorbed (f(abs)) and effective permeability (P(eff)) of phenoxymethylpenicillin were 0.3% and 0.06 x 4 cm s(-1), respectively, and remained unaffected by the addition of sodium caprate . When the same subjects were perfused at pH 7.4, the f(abs) and P(eff) of phenoxymethylpenicillin were 2.4% and 0.11 x 10(-4) cm s(-1) (0-100 min), respectively, also remaining unchanged by addition of sodium caprate (100-200 min) . It was possible to determine the plasma AUC of phenoxymethylpenicillin after addition of sodium caprate in three subjects at both pHs; this was in the range of 14.0-62.8 and 56.4-231 (min micromol L(-1)) at pH 6.0 and 7.4, respectively . Interestingly, there was a correlation between P(eff) for sodium caprate and the individual plasma AUC and C(max) of phenoxymethyl-penicillin, which indicates that the permeability of the enhancer in the tissue upon which it should act is crucial for achieving an effect . The f(abs) and the P(eff) of antipyrine were not affected at either pH when sodium caprate was added to the perfusion solution . In conclusion, the plasma pharmacokinetics of phenoxymethylpenicillin suggested a slightly increased rectal absorption at pH 7.4 in subjects where sodium caprate was transported into the rectal tissue . However, the increased P(eff) for phenoxymethylpenicillin wastoo small to detectfrom the outlet perfusate, which suggests that sodium caprate alone has a limited effect on the permeability in-vivo across the rectal epithelium when it is presented in a solution.

Appl Biochem Biotechnol, 2002 Mar, 97(3), 181 - 92
Application of spontaneous suction phase-dispersing (SSPD) extractors in the extraction of penicillin G; Chen J et al.; The extraction of penicillin G from an aqueous solution with butyl acetate (BA) and tributyl phosphate (TBP) as extractants was carried out at pH 4 with spontaneous suction phase-dispersing (SSPD) extractors under various operating conditions . Four kinds of SSPD extractors were tested with results compared to those obtained by using an extractor with mechanical stirrers . Rotation speed and different extraction systems were found to influence the penicillin recovery and the stability of emulsion formed during extraction . The percentage of extraction under optimum conditions was 91% without formation of emulsion . The laser particle size measurement instrument combined with SSPD can be used to measure the emulsion droplet size in situ.

Appl Biochem Biotechnol, 2002 Mar, 97(3), 165 - 79
Optimization of yield in kinetically controlled synthesis of ampicillin with immobilized penicillin acylase in organic media; Illanes A et al.; Immobilized penicillin acylase is a moderately priced versatile enzyme, that is able to catalyze the synthesis of derived penicillins and cephalosporins from the corresponding beta-lactam nuclei and proper side-chain precursors . Kinetically controlled synthesis is a better strategy when product yield is a key issue . Yield should increase at reduced water activity by depressing the competing hydrolytic reactions in favor of synthesis; therefore, organic cosolvents can be a suitable reaction media for synthesis . Using response surface methodology and product yield as objective function, temperature and pH were optimized in the kinetically controlled synthesis of ampicillin using previously screened cosolvents and reaction conditions . Optimum pH was 6.0 for ethylene glycol (EG) and glycerol (GL) and 6.6 for 1-2 propanediol (PD); optimum temperature was 30 degrees C for GL and for EG and PD was in the lower extreme of the range studied, optimum lying below 26 degrees C . Maximum molar yields predicted by the model were 58,51, and 46% for EG, GL, and PD, respectively, which were experimentally validated . Highest yield in aqueous buffer was always <40% . Molar yields about 60% compare favorably with values reported for the kinetically and thermodynamically controlled synthesis of ampicillin and other derived penicillins.

Ann R Coll Surg Engl, 2002 Mar, 84(2), 106 - 8
Splenectomy after paediatric trauma: could more spleens be saved?
Godbole P, Stringer MD.
AIMS: Guidelines for the emergency management of paediatric splenic trauma became widely available in 1993 . A regional survey was undertaken to assess the application of Advanced Paediatric Life Support guidelines to children who had undergone splenectomy after trauma . PATIENTS AND METHODS: All children who had undergone splenectomy for a ruptured spleen at 8 district hospitals and 2 teaching hospitals in our region between January 1994 and January 1999 were identified from histopathology departmental records . With appropriate permission their case notes were reviewed . RESULTS: Eleven children (9 males) were identified, all from district hospitals, with a median age at presentation of 11.8 years (range, 6.6-16.8 years) . All presented within 6 h of blunt abdominal trauma . Median systolic blood pressure, pulse rate, haemoglobin concentration and injury severity score (ISS) on admission were 115 mmHg (range, 80-140 mmHg), 108 bpm (range, 84-150 bpm), 12.1 g/dl (range, 10.7-12.8 g/dl) and 17 (range, 17-29), respectively . Three children had additional relatively minor injuries . On admission, 3 children received an intravenous fluid bolus of 20 ml/kg and the remainder received only maintenance fluid requirements or less . Five children were investigated by ultrasound imaging, one by double contrast CT scan, and three by laparoscopy . Two children had no imaging studies prior to laparotomy . Laparotomy was performed by a consultant surgeon in 7 cases and by a specialist registrar in 4 cases . Ten children underwent total splenectomy and one child had a partial splenectomy . Median hospital stay was 7 days (range, 5-10 days) . The child with an ISS of 29 developed a persistent pancreatic fistula and subsequently required a distal pancreatectomy . All children received Pneumovax and penicillin prophylaxis . CONCLUSIONS: All children made a full recovery without surgical morbidity . However, none of these cases fulfilled the recommended criteria for laparotomy in children with blunt abdominal trauma and splenectomy may have been avoidable.

Intern Med, 2002 Apr, 41(4), 319 - 22
Pulmonary actinomycosis followed by pericarditis and intractable pleuritis; Shinagawa N et al.; A case of pleuropericarditis caused by Actinomyces israelli is described . The patient first underwent left upper lobectomy because of pulmonary actinomycosis . Seven months later, cardiac tamponade developed . Culture of the bloody pericardial effusion resulted in positive growth of Actinomyces israeli . He was successfully treated with penicillin G, ampicillin, and minocyclin . However, right pleural effusion appeared two months later . Cultures of the effusion again yielded positive growth of the same bacteria . However, the strain had gained resistance to any antibiotics that had been effective before . Accordingly, pleurodesis with minocyclin was undertaken, which was fortunately effective for controlling the pleural effusion.

J AOAC Int, 2002 Mar-Apr, 85(2), 355 - 64
Parallux beta-lactam: a capillary-based fluorescent immunoassay for the determination of penicillin-G, ampicillin, amoxicillin, cloxacillin, cephapirin, and ceftiofur in bovine milk; Huth SP et al.; An analytical system was developed for detection of antibiotic residues in bovine milk . The method is based on competitive fluorescent immunoassays in glass capillary tubes (U.S . Patent No . 5,624,850) . The system consists of an assay cartridge containing 4 glass capillaries, a reagent tray with 4 wells of dried reagents, and a Parallux processor, which processes the assay, reads fluorescent output, and reports test results . Minimum sensitivity for detection of 6 beta-lactam antibiotics in bovine milk was determined to be penicillin-G, 3.2 ppb; ampicillin, 2.9 ppb; amoxicillin, 3.6 ppb; cloxacillin, 7.4 ppb; cephapirin, 16.3 ppb; and ceftiofur, 33.7 ppb . The assay system was also specific and sensitive for detection of incurred residues at U.S . Food and Drug Administration tolerance levels: penicillin-G, 5 ppb; ampicillin, 10 ppb; amoxicillin, 10 ppb; cloxacillin, 10 ppb; cephapirin, 20 ppb; and ceftiofur, 50 ppb . There was no interference in detection of minimum sensitivity levels of antibiotic by the presence of somatic cells at approximately 1 x 10(6) cells/mL . Milk containing 3 x 10(6) cells/mL bacteria commonly found in mastitic milk also showed no interference when tolerance levels of antibiotic were present . There was no detectable interference on results by a wide variety of non-beta-lactam drugs.

An Med Interna, 2002 Feb, 19(2), 89 - 95
{Syphilis: current therapeutic perspectives}; Pestoni Porven C et al.; Despite many years of study questions regarding the appropriate therapy for syphilis still remain . Alternatives to penicillin for the treatment of syphilis continue to be sought . This article examines the studies relating to syphilis treatment published during the last years and also the new treatment guidelines for every stage of this sexually transmitted disease.

Przegl Lek, 2001, 58(11), 975 - 8
{Drug allergy among patients suffering from nasal polyps}; Skladzien J et al.; The study was performed in order to evaluate quantity and morphology of nasal polyps in patients with diagnosed drug allergy to aspirin, antibiotics, polocain, procain and other drugs . The study included 60 patients (27 females, 33 males aged between 18-69 years) . Nasal polyp morphology was examined under electron microscope and light microscope . Morphological evaluation of epithelial and subepithelial structures was done under light microscope, taking not of inflammatory infiltration type, basal membrane, as well as degree of intestinal edema . Evaluation of epithelial cell type, their relative proportion, as well as area percentage covered by cilium, microvilli and squamous epithelium was done under electron microscope . Polyps in patients with idiosyncrasy to polish aspirin and sodium metamizole (12 patients) featured increased eosinophilic infiltration, thickened basal membrane, with elevated eosinophil percentage differential count . The epithelial percentage area was covered by squamous cells without villi . Polyps associated with idiosyncrasy to polish aspirin differed morphology compared to polyps originality from patients allergic to other medications . On the other hand polyps from patients allergic to other drugs, such as: penicillin, procainamide were morphologically (electron light microscope, light microscope) similar to those polyps caused by inflammatory factors.

Eur J Biochem, 2002 Apr, 269(8), 2093 - 100
The role of hydrophobic active-site residues in substrate specificity and acyl transfer activity of penicillin acylase; Alkema WB et al.; Penicillin acylase of Escherichia coli catalyses the hydrolysis and synthesis of beta-lactam antibiotics . To study the role of hydrophobic residues in these reactions, we have mutated three active-site phenylalanines . Mutation of alphaF146, betaF24 and betaF57 to Tyr, Trp, Ala or Leu yielded mutants that were still capable of hydrolysing the chromogenic substrate 2-nitro-5-{(phenylacetyl)amino}-benzoic acid . Mutations on positions alphaF146 and betaF24 influenced both the hydrolytic and acyl transfer activity . This caused changes in the transferase/hydrolase ratios, ranging from a 40-fold decrease for alphaF146Y and alphaF146W to a threefold increase for alphaF146L and betaF24A, using 6-aminopenicillanic acid as the nucleophile . Further analysis of the betaF24A mutant showed that it had specificity constants (kcat/Km) for p-hydroxyphenylglycine methyl ester and phenylglycine methyl ester that were similar to the wild-type values, whereas the specificity constants for p-hydroxyphenylglycine amide and phenylglycine amide had decreased 10-fold, due to a decreased kcat value . A low amidase activity was also observed for the semisynthetic penicillins amoxicillin and ampicillin and the cephalosporins cefadroxil and cephalexin, for which the kcat values were fivefold to 10-fold lower than the wild-type values . The reduced specificity for the product and the high initial transferase/hydrolase ratio of betaF24A resulted in high yields in acyl transfer reactions.

J Gastroenterol Hepatol, 2002 Apr, 17(4), 482 - 7
Update on the management of Helicobacter pylori infection, including drug-resistant organisms; Goh KL; Helicobacter pylori infection has many different clinical outcomes . Not all infected persons need to be treated . Therefore, indications for treatment have to be clear, and several consensus guidelines have been formulated to aid the medical practitioner in this decision-making process . Triple therapy with a proton pump inhibitor (PPI), in combination with amoxicillin and clarithromycin is the established treatment of choice . For patients with penicillin hypersensitivity, metronidazole can be substituted for amoxicillin . Bacterial resistance to antibiotics is a major factor adversely affecting treatment success . Resistance to metronidazole has been reported in up to 80%, and resistance to clarithromycin in 2-10% of strains cultured . Resistance to either one of the antibiotics has been reported to result in a drop in efficacy of up to 50% . Emergence of resistance to both metronidazole and clarithromycin following failed therapy is a cause for concern; this underlines the need to use the best available first-line therapy . To avoid the emergence of resistance to both key antibiotics, the combination of metronidazole and clarithromycin should be avoided where possible . For failed treatment, several strategies can be employed . These include ensuring better compliance with repeat therapy, and maximizing the efficacy of repeat treatment by increasing dosage and duration of treatment, as well as altering the choice of drugs . Quadruple therapy incorporating a bismuth compound with a PPI, tetracycline and metronidazole has been a popular choice as a "rescue" therapy . Ranitidine bismuth citrate has been shown to be able to overcome metronidazole and clarithromycin resistance; it may be a useful compound drug to use in place of a PPI in "rescue" therapies . In the case of persistent treatment failures, it is useful to consider repeating gastroscopy and obtaining tissue for culture, and then prescribe antibiotics according to bacterial susceptibility patterns . It is also important in refractory cases to review the original indication for treatment and determine the importance of the indication .

Curr Opin Infect Dis, 2001 Apr, 14(2), 133 - 7
Lyme disease in central Europe; Hercogova J et al.; Lyme borreliosis is a fascinating disease, the aetiopathology of which is not yet completely known . Different subspecies of Borrelia burgdorferi sensu lato are responsible for the variable clinical course of the disease . Some new cutaneous (alopecia) and ocular (photophobia and retinal vasculitis) manisfestations have been described and the largest prospective study on erythema migrans during pregnancy was published during the last year . Optimal therapy of Lyme borreliosis is still lacking, but doxycycline, amoxicillin, penicillin, and ceftriaxone are recommended most frequently.

Altern Lab Anim, 2002 Mar-Apr, 30(2), 177 - 98
Selection of test chemicals for the ECVAM international validation study on in vitro embryotoxicity tests . European Centre for the Validation of Alternative Methods; Brown NA; The European Centre for the Validation of Alternative Methods (ECVAM) has sponsored a large international prevalidation and validation study of three embryotoxicity tests, involving embryonic stem cells, limb bud micromass cultures, and post-implantation whole-embryo cultures . The main objective of the study was to assess the performance of these in vitro tests in discriminating between non-embryotoxic, weakly embryotoxic and strongly embryotoxic compounds . An initial part of the study was to select 20 test substances for the formal validation trial, conducted under blind conditions . A database of in vivo and in vitro developmental toxicity test results was complied on 310 chemicals that had been used in previous validation studies, or suggested for such use, or that had good quality "segment II"-type in vivo data, or for which there were human data . From this database, a shortlist of about 30 candidates was constructed . Because the ECVAM study would not include metabolic activation, chemicals known to require activation for their developmental effects were excluded as candidates, although some known stable metabolites were included . Attempts were made: to include substances of diverse mechanism; to avoid overemphasis on pharmaceuticals; to avoid biologically inert substances as non-embryotoxicants; and to make the list different from those used previously . The candidates were of three categories: Class 3, strongly embryotoxic, was defined as developmentally toxic in all species tested, inducing multiple developmental effects, and with a high A/D ratio . Class 1, non-embryotoxic, was defined as not developmentally toxic at maternally toxic exposures, but which may show some minor embryo/fetal toxicity, which cannot be separated from maternal toxicity . Class 2, weakly embryotoxic, were chemicals of intermediate activity . From this candidate list, chemicals of known receptor (androgen, oestrogen, glucocorticoid, aryl hydrocarbon) mechanisms were excluded, on the basis that simple tests for such activity are already available . In addition, chemicals not freely available were excluded, and an emphasis on human data was applied . The final list of 20 chemicals was: Class 3--6-aminonicotinamide, 5-bromo- 2'-deoxyuridine, hydroxyurea, methylmercury chloride, methotrexate, all-trans-retinoic acid; Class 2--boric acid, dimethadione, lithium chloride, methoxyacetic acid, valproic acid (VPA), 2-propyl-4-pentynoic acid (4-yn-VPA), salicylic acid sodium salt; and Class 1--acrylamide, D-(+)-camphor, dimethyl phthalate, diphenhydramine hydrochloride, 2-ethyl-4- methylpentanoic acid (isobutyl-ethyl-VPA), Penicillin G sodium salt, saccharin sodium hydrate.

Ned Tijdschr Geneeskd, 2002 Apr 6, 146(14), 668 - 71
{Tetanus in a young unvaccinated girl after a fall in the street}; Dolman KM et al.; A 4-year-old girl developed tetanus after she had fallen on the street a week before . She had never been vaccinated and despite pressure from the family practitioner, the parents refused to allow her to be given human anti-tetanus immunoglobulin as a matter of principle after the wound had been stitched . Seven days later she was admitted to hospital with trismus and risus sardonicus . Upon initial treatment with human anti-tetanus immunoglobulin and penicillin, and subsequently metronidazole, her clinical condition deteriorated with opisthotonus and life-threatening respiratory insufficiency, upon which she was moved to the intensive-care department where she was intubated and mechanically ventilated for two weeks . Finally she made a complete clinical recovery . Thanks to the extensive national vaccination program, tetanus has become a rare disease in the Netherlands . However, the very serious course and possible fatal outcome warrant a keen attitude and adequate treatment.

Scand J Immunol, 2002 Apr, 55(4), 390 - 8
Chlamydia pneumoniae inhibits apoptosis in human epithelial and monocyte cell lines; Airenne S et al.; Chlamydia pneumoniae is an obligate intracellular pathogen with a tendency to cause persistent infections that has been associated with many chronic conditions such as asthma and coronary artery disease . However, its immunopathogenic mechanisms are poorly understood . When aiming to study the impact of C . pneumoniae infection on host cell apoptosis, we found that epithelial infected (HL) cells and macrophages (U937-line) were resistant to staurosporine and tumour necrosis factor (TNF)-alpha-induced physiological apoptosis 48, 72 or 120 h post-infection, as determined by flow cytometry, DNA fragmentation assay and fluorescence microscopy . The antiapoptotic influence was observed even at a late stage of the chlamydial life cycle and was dependent on the chlamydial protein synthesis . The mechanisms involved blockage of mitochondrial cytochrome c release and caspase 3 activation . We also found that during a persistent C . pneumoniae infection induced in vitro by penicillin treatment of cell cultures, the inhibition of apoptosis was extended for up to 120 h of follow-up post-infection and was restricted to the cells carrying chlamydial inclusions . Our findings suggest that inhibition of apoptosis may be one of the pathogenetic mechanisms by which C . pneumoniae infection can mediate the development of chronic diseases.

Sheng Li Xue Bao, 2000 Apr, 52(2), 131 - 6
{The role of somatostatin in area CA1 of rat hippocampus in experimental epilepy}; Zhao WJ et al.; In area CA1, intrahippocampal microinjection of somatostatin(SS, 0.03 to 0.3 nmol) caused single or a series of spike-sharp waves in the cortex electroencephalogram (EEG), the spectrum average total power of which is increased dose-dependently from 0.006 to 0.15 nmol . Microinjection of SS into the hippocampal CA1 subregion brought out epileptic-like behavioral responses and aggregated kainic acid (KA)-induced epileptiform activity of rats . With extracellular recording technique, the effects of SS on 114 units epileptiform discharge were investigated in penicillin (PEN)-treated 95 rat hippocampal slices . In response to the application of SS (10(-10), 10(-8), 10(-6) mol/L), the burst frequency of area CA1 62/105 (59.05%) recorded unit discharges was increased significantly, while that of 23/105 (21.9%) was decreased . These results suggest that SS in hippocampal CA1 subregion mainly precipitates epileptiform discharge . The addition of anti-somatostatin antibody (1 1000) to the perfusate partly blocked the epileptiform bursts triggered by PEN perfusion, while this antiepileptic effect of SSAB was reversed by application of SS (10(-8) mol/L) . These indicate that endogenous SS may be involved in epileptiform discharge in area CA1 of hippocampus.

Antimicrob Agents Chemother, 2002 May, 46(5), 1273 - 80
Effects of amino acid alterations in penicillin-binding proteins (PBPs) 1a, 2b, and 2x on PBP affinities of penicillin, ampicillin, amoxicillin, cefditoren, cefuroxime, cefprozil, and cefaclor in 18 clinical isolates of penicillin-susceptible, -intermediate, and -resistant pneumococci; Nagai K et al.; Amino acid alterations in or flanking conserved motifs making up the active binding sites of penicillin-binding proteins (PBPs) 1a, 2b, and 2x of pneumococci were correlated with changes in affinities of penicillin, ampicillin, amoxicillin, cefditoren, cefuroxime, cefprozil, and cefaclor for these PBPs . Four penicillin-susceptible (PSSP), eight penicillin-intermediate (PISP), and six penicillin-resistant (PRSP) pneumococci were studied by DNA sequencing of the penicillin-binding sites of the pbp1a, -2x, and -2b genes of strains and by determining 50% inhibitory concentrations of the seven agents for PBP1a, -2x, and -2b . Two PSSP strains had alterations in PBP2x (L(546)-->V) (one strain) or PBP2b (T(445)-->A) (one strain) . All eight PISP strains had at least two alterations--T(338)-->P or A or H(394)-->Y in PBP2X and T(445)-->A in BPB2b . All PRSP strains had the same changes seen in PISP strains, as well as T(371)-->A or S substitutions in PBP1a . The two most resistant PRSP strains had a second change in PBP2x (M(339)-->F) in a conserved motif . The affinities of penicillin and ampicillin for all three PBPs were decreased for PRSP and most PISP strains . The affinity of amoxicillin for PBP1a and -2x was decreased only for PRSP . Cefaclor and cefprozil showed decreased affinity of PRSP but not PISP for all three PBPs . Cefuroxime showed decreased affinity of PISP and PRSP for PBP1a and -2x but no change for PBP2b . Cefditoren showed no difference in PBP affinity based on penicillin or cefditoren MICs, indicating a different PBP target for this agent . Overall, the MICs for and PBP affinities of the strains correlated with the changes found in the PBP active binding sites.

Ethiop Med J, 1999 Jul, 37(3), 155 - 61
Rheumatic heart disease among school children in Addis Ababa City: awareness and adequacy of its prophylaxis; Oli K et al.; One of the objectives of this large scale cross-sectional study of school children of the Addis Ababa city was to assess the status of rheumatic heart disease (RHD) prophylaxis among rheumatic heart disease patients identified during the survey . Awareness about the presence of the illness in those affected and reasons for poor coverage, when detected, were also assessed . Sixty of the 9388 school children surveyed were found to have rheumatic heart disease . On interviewing parents of the children with rheumatic heart disease, ten acknowledged being informed of their children's cardiac illness . Of these parents, 15% (or 9/60) had some idea that their children had heart disease related to some form of infection . However, only two of the nine (22%) children whose parents had some idea about their disease were on regular monthly benzathine penicillin prophylaxis in the previous 12 months preceding the interview . Three (33%) of the nine children had six or fewer injections in the 12 months preceding the interview . The remaining 4 parents (44%) reported that their children took treatment that included injections only at the time of initial diagnosis several years earlier and had not had any follow up since then . Their reasons for not seeking medical care for their children included lack of information on prophylaxis, inability to pay for the treatment and distance of the health facilities . The lack of awareness and the extremely low rate of regular prophylaxis, therefore, highlight the need for an urgent control programme that takes active case detection, treatment access and health education into consideration.

Cent Afr J Med, 2001 Feb, 47(2), 35 - 8
Injection-induced sciatic nerve injury in Nigerian children; Fatunde OJ et al.; OBJECTIVES: A retrospective study of all children with a diagnosis of sciatic nerve injury managed at the University College Hospital, Ibadan, Nigeria over a 12 year period was carried out in order to determine predisposing factors to the nerve injury and highlighting practical preventive measures . DESIGN: The necessary data was collected from the case files of children seen at the hospital with a diagnosis of sciatic nerve injury, from 1988 to 1999 . RESULTS: There were 27 children aged five months to 12 years with a diagnosis of sciatic nerve injury . Twenty (74%) of the children were aged five years or less . While seven patients (26%) presented within two weeks of development of foot drop consequent on intramuscular (i.m.) injection given on the buttock, 20 patients (74%) presented much later . Fever was the most common complaint for which the injection had been given . The identity of the drugs given was not known in 10 patients . In the remaining 17 patients drugs administered were specified and included Chloroquine, Novalgin, Paraldehyde, Procaine penicillin, and Sulfadoxine-Pyrimethamine . Most of the patients had received the injections in privately owned medical facilities where staff with minimal training are often allowed to administer i.m . injections . CONCLUSION: It is suggested that the i.m . route for injection be strongly discouraged when a drug can be given by other routes . Only trained staff should be allowed to administer i.m . injections . Giving i.m . injections at sites other than the buttock maybe advantageous in children particularly those aged five years and below.

Sheng Wu Yi Xue Gong Cheng Xue Za Zhi, 2002 Jan, 19(1), 36 - 9
{Investigation on culture of rat pulmonary microvascular endothelial cells and their viscoelasticity}; Li F et al.; It is the infent of this study to establish a simple method for cultivation of rat pulmonary microvascular endothelial cells(PMVECs) and investigate the viscoelasticity of PMVECs . First, we obtained rat's peripheral pulmonary tissue, which then was cut into small pieces and cultured with 3 ml DMEM containing 20% bovine calf serum, 90 U/ml heparin, 4 mmol L-glutamine, 100 U/ml penicillin and 100 micrograms/ml streptomycin . Next, moved away the pulmonary tissue pieces 60 h later, and started passage 2-4 days after continued culture . Last, digested and separated PMVECs and studied viscoelastic coefficients of PMVECs by using micropipette aspiration technique . The results revealed that the cultured PMVECs showed regular cobblestone morphology and conformed with endothelial cells morphological characterization by phase contrast microscopy . PMVECs elastic modulus K1 was 49.3 +/- 9.2 Pa, K2 was 73.2 +/- 24.8 Pa, and it's viscosity factor mu was 19.2 +/- 7.2 Pa . s . These data demonstrate that it is feasible to cultivate PMVECs with tissue pieces method, and PMVECs is of greater rigidity.

Biotechnol Bioeng, 2002 May 20, 78(4), 425 - 32
Evaluation of the performance of immobilized penicillin G acylase using active-site titration; Janssen MH et al.; Penicillin G acylase from Escherichia coli was immobilized on Eupergit C with different enzyme loading . The activity of the immobilized preparations was assayed in the hydrolysis of penicillin G and was found to be much lower than would be expected on the basis of the residual enzyme activity in the immobilization supernatant . Active-site titration demonstrated that the immobilized enzyme molecules on average had turnover rates much lower than that of the dissolved enzyme . This was attributed to diffusion limitations of substrate and product inhibition . Indeed, when the immobilized preparations were crushed, the activity increased from 587 U g-1 to up to 974 U g-1 . The immobilized preparations exhibited up to 15% lower turnover rates than the dissolved enzyme in cephalexin synthesis from 7-ADCA and D-(-)-phenylglycine amide . The synthesis over hydrolysis ratios of the immobilized preparations were also much lower than that of the dissolved enzyme . This was partly due to diffusion limitations but also to an intrinsic property of the immobilized enzyme because the synthesis over hydrolysis ratio of the crushed preparations was much lower than that of the dissolved enzyme .

Lett Appl Microbiol, 2002, 34(4), 290 - 2
Improvement in the resting-cell bioconversion of penicillin G to deacetoxycephalosporin G by addition of catalase; Gao Q et al.; AIMS: To improve the resting cell bioconversion of penicillin G to deacetoxycephalosporin G (DAOG) by elimination of an oxidizing intermediate which inactivates the enzyme during the reaction . METHODS AND RESULTS: Resting cells of Streptomyces clavuligerus strain NP1 were incubated with penicillin G, required co-factors and decane in the presence of catalase or superoxide dismutase, and production of DAOG was measured . Catalase stimulated the bioconversion but superoxide dismutase did not . CONCLUSIONS: Production of hydrogen peroxide during the ring expansion reaction is at least partially responsible for enzyme inactivation . SIGNIFICANCE AND IMPACT OF THE STUDY: Catalase addition improves the bioconversion and will contribute to the eventual replacement of the current multi-step, expensive and environmentally-unfriendly chemical ring expansion by a biological route.

Ann Dermatol Venereol, 2002 Feb, 129(2), 207 - 11
{Cutaneous polyarteritis nodosa in children: three cases}; Assicot C et al.; INTRODUCTION: Polyarteritis nodosa is a necrotizing vasculitis of small and medium-size arteries . The cutaneous form of polyarteritis nodosa follows a chronic course, characterized by recurrent episodes limited to skin, muscles and joints . This entity differs from systemic polyarteritis nodosa in the absence of visceral involvement . This form is rare in children, we describe three cases . CASE REPORTS: We describe three girls with a mean age of 11 years (range: 8-13) . They presented painful subcutaneous edematous nodules, arthralgia and fever . Physical examination revealed livedo reticularis (2 cases) and pharyngeal infection (1 case) . Laboratory findings showed an inflammatory syndrome . Skin biopsy supported diagnosis of polyarteritis nodosa . The course was characterized by periods of remission disrupted by exacerbations, well controlled by salicylotherapy, colchicine, dapsone or penicillin . Corticosteroid therapy was used only for invalidating symptoms . There was no systemic involvement after 2, 5 and 6 years of follow up . DISCUSSION: Cutaneous polyarteritis nodosa in children must be suspected in presence of fever, subcutaneous nodules, livedo reticularis and arthralgia . Prognosis is usually benign, so we recommend no aggressive treatment . In view of the tendency to relapse, long-term follow-up is appropriate, before confirming diagnosis.

Parasitol Res, 2002 Feb, 88(2), 172 - 4
An anti-contamination cocktail for the in vitro isolation and cultivation of parasitic protozoa; Maser P et al.; Contamination by bacteria or fungi is a frequent problem with the in vitro isolation and propagation of protozoan parasites . We developed an antibiotic combination of broad anti-contaminant activity but minimal toxicity to protozoa . This anti-contamination cocktail consists of penicillin G (60 microgml(-1)), kanamycin (100 microgml(-1)), chloramphenicol (10 microgml(-1)) and flucytosine (50 microgml(-1)) . It is well tolerated by African and South American trypanosomes, Leishmania spp., Giardia duodenalis, Entamoeba histolytica and Plasmodium falciparum, and it provides an effective means for the treatment of contaminated cultures . The anti-contamination cocktail meets numerous prophylactic applications in which sterile handling is impracticable or impossible . In particular, it facilitates the direct in vitro isolation of parasites from an infected host.

Biotechnol Prog, 2002 Mar-Apr, 18(2), 163 - 6
Reciprocal 13C-labeling: a method for investigating the catabolism of cosubstrates; Christensen B et al.; The principle of reciprocal labeling is to use a uniformly 13C-labeled substrate as the primary carbon source and a naturally labeled cosubstrate . Metabolites derived from a naturally labeled cosubstrate, in this case amino acids, can then be identified by their relatively lower content of 13C, and information on the degradation pathway can be deduced . The technique is based on GC-MS measurements of amino acid labeling patterns, making the technique well suited for investigating the relative importance of amino acid biosynthesis and amino acid uptake from the medium, as the 13C content of the amino acids incorporated into biomass is a direct measure of the amino acid biosyntheses . The technique is illustrated by the investigation of the degradation of phenoxyacetic acid, a medium component that is essential for production of penicillin V by Penicillium chrysogenum . Glucose was used as the uniformly labeled primary carbon source.

Chembiochem, 2002 Apr 2, 3(4), 332 - 40
Moenomycin-mediated affinity purification of penicillin-binding protein 1b; Stembera K et al.; The antibiotic moenomycin A inhibits the biosynthesis of peptidoglycan, the main structural polymer of the bacterial cell wall . The inhibition is based on a reversible binding of the antibiotic to one of the substrate binding sites at enzymes such as the penicillin binding protein 1b (PBP 1b) . This binding has been employed to isolate PBP 1b by affinity chromatography . Suitable ligands have been prepared from moenomycin A and coupled both to affinity supports and to surface plasmon resonance sensor surfaces . The reactions that take place upon immobilization of the ligands to the affinity support and the sensor surface, respectively, have been studied in detail . With the help of surface plasmon resonance the optimal conditions for binding of PBP 1b to moenomycin-derivated ligands have been established . For the first time the selective binding of the moenomycin sugar moiety to the enzyme has been demonstrated.

Psychiatry Clin Neurosci, 2002 Feb, 56(1), 65 - 70
Cerebral blood flow changes in general paresis following penicillin treatment: a longitudinal single photon emission computed tomography study; Kitabayashi Y et al.; Three cases of general paresis were successfully treated with high-dose penicillin . In all cases, cerebrospinal fluid cell counts decreased to normal and mental status improved rapidly . Cerebrospinal fluid protein concentrations decreased and IQ scores and overall levels of functioning improved gradually over 1 year . Regional cerebral blood flow (CBF) changes were analyzed longitudinally for 1 year using single photon emission computed tomography (SPECT) . Autoradiography method and region of interest (ROI) analyses were used for quantitative CBF assessment and 3D stereotactic surface projections (3D-SSP) analyses were used for qualitative CBF pattern assessment . 3D-SSP could not reveal remarkable CBF pattern changes through the courses . The ROI analyses showed remarkable CBF decreases in all brain regions 1 month after the treatment, which recovered to normal levels 1 year after the treatment . These results suggest that remarkable decreases of quantitative CBF counts reflect the disappearance of encephalitis, while their gradual recovery reflects the gradual improvement of cerebral functional activity . As Treponema pallidum infection affects whole brain and CBF changes globally, quantitative CBF assessment may be more efficient than qualitative CBF pattern analyses for the purpose of understanding the pathophysiology of general paresis.

Clin Exp Allergy, 2002 Feb, 32(2), 270 - 6
Controlled administration of penicillin to patients with a positive history but negative skin and specific serum IgE tests; Torres MJ et al.; BACKGROUND: Although subjects with a positive history of immediate allergy to penicillin and negative skin test are traditionally considered to tolerate penicillin, current evidence indicates that they may develop an immediate reaction despite negative skin and serum specific IgE tests . It is thought that these patients require additional tests to confirm the diagnosis . OBJECTIVE: To assess in a large group of patients with a history of immediate allergy to penicillins but with both skin test and CAP-FEIA-negative to classical and side chain penicillin determinants, the role of controlled administration of betalactams as a diagnostic test . METHODS: A group of 330 patients with a history of immediate allergic reactions to penicillins was studied by two evaluators from the same allergy unit using the following protocol: skin tests with major and minor determinants of benzylpenicillin (benzylpenicilloyl-poly l-lysine and minor determinant mixture), amoxicillin and ampicillin, and determination of specific IgE antibodies to penicillins, by CAP-FEIA, in serum . If both tests proved negative, a controlled administration of the drug was then carried out . RESULTS: A total of 89 (27%) patients were skin test and CAP-FEIA-negative and therefore required controlled administration of the drug . Of these, 49 developed an immediate response and were therefore considered allergic, and the remainder had good tolerance after administration of both benzylpenicillin and amoxicillin . The clinical characteristics of this group were similar to the other allergic patients who were skin test or CAP-FEIA-positive, except that they were younger (P < 0.01) . Twenty-two (45%) developed a response to benzylpenicillin and 27 (55%) had a selective response to amoxicillin . Although all reactions appeared within 1 h, a positive correlation was found between the dose inducing the response and the time elapsed from drug administration, for both benzylpenicillin and amoxicillin (P < 0.001) . CONCLUSION: These data indicate that an important number of subjects are not correctly identified if only skin tests and/or CAP-FEIA are used and that this is particularly relevant for side chain-specific reactions and younger subjects . This suggests that new diagnostic tests are required so as to limit the use of controlled administration.

Scand J Infect Dis, 2002, 34(2), 88 - 92
Nosocomial transmission of syphilis during haemodialysis in a developing country; Saxena AK et al.; Patients with end-stage renal disease (n = 187) secondary to diverse aetiologies who underwent haemodialysis (HD) between November 1996 and November 2000 were routinely screened for syphilis using the rapid plasma reagin (RPR) test and confirmed by means of a microhemagglutination assay for Treponema pallidum . All the confirmed syphilis patients were asymptomatic and were diagnosed serologically . A true seroprevalence of 6.9% (13/187) and a biological false seropositivity of 4.2% (8/187) for syphilis were recorded . Most (11/13) of the true seropositive patients were aged between 51 and 80 y . Whilst 10/13 patients were true syphilis seropositive at the time of first HD, 3/13 patients became true seropositive an average of 12 months (range 10-14 months) after HD . Penicillin treatment was given to all 13 patients simultaneously only after the appearance of 3 new true syphilis seropositive cases . Complete seroreversion was observed in 4/10 patients in the pre-HD true syphilis seropositive group of presumptive transmitters who became RPR-negative, whereas the 3 new true seropositive cases showed a serial 4-fold decline in RPR titres 12 months after penicillin therapy, suggestive of an active disease with adequate therapeutic response . These results clearly indicate that latent syphilis is prevalent in long-term elderly HD patients . The true seroconversion of 3 new patients who had undergone HD for an average of 12 months is indicative of nosocomial transmission and the silently active nature of the disease, which necessitates regular monitoring of syphilis serology among HD patients.

ALTEX, 2002, 19(1), 15 - 20
Novel serum replacement based on bovine ocular fluid: a useful tool for cultivation of different animal cells in vitro; Filipic B et al.; Different mammalian cells in culture have individual nutritional requirements, which are mainly fulfilled by the addition of foetal calf serum (FCS) to the basic medium . Collecting FCS is accompanied with severe animal welfare problems as conscient animals usually are bleeded to death by heart-punctuation without anaesthetics . There exists scientific problems too . Due to the batch-to-batch variability and the relatively high price, different types of serum replacements were introduced . Among them bovine colostrum as a serum substitute for the cultivation of hybridoma cells should be mentioned . The presented experiments were aimed to introduce the simple and effective serum replacement (SR) based on the bovine ocular fluid . Throughout the experiments the bovine ocular fluid alone and in the combination with the sheep's defibrinated plasma and human serum albumin was tested for the growth of different cells growing as a monolayer: (a) Cell lines: WISH (human amniotic cell lines) and VERO . (b) Primary culture: chicken embryonic fibroblasts, human bone-marrow fibroblasts . All growth experiments were performed in parallel with the Foetal Calf Serum (FCS) of three different sources . All types of cells were cultivated in Eagle's medium + antibiotics (Penicillin, Streptomycin, Gentamycin) . The most effective was the SR containing approximately 35% of sheep's defibrinated plasma and 1.5% of serum albumin in the bovine ocular fluid . During the experiments 1 and 10% of SR-2.05 or FCS in Eagle's medium were used . After 1, 3 and 6 days of cultivation the cells were counted . The results show that the use of SR-2.05 gives a higher number of cells as compared to most batches of FCS . It is also important that practically no adaptation is needed, meaning that the cells could be grown in Eagle's medium + FCS and in the next passage in Eagle's medium + SR-2.05 and vice versa.

Pediatrics . 2002 Apr;109(4):e63.
Survival with hypopituitarism from congenital syphilis; Nolt D et al.; Congenital syphilis continues to occur despite the advances in testing of pregnant women in many countries and the availability of penicillin since 1943 . This is a report of a child with multiple systemic manifestations of congenital syphilis . This is one of the few cases of survival with pituitary involvement from congenital syphilis and the first noted case in which diabetes insipidus developed . Institution of routine testing in all countries might have prevented the severe manifestations of syphilis seen in this child.

Arch Intern Med, 2002 Apr 8, 162(7), 822 - 6
Lack of penicillin resensitization in patients with a history of penicillin allergy after receiving repeated penicillin courses; Solensky R et al.; BACKGROUND: Up to 10% of the population reports an allergy to penicillin, yet more than 80% of these individuals lack penicillin-specific IgE antibodies . A negative result on a penicillin skin test is highly accurate in identifying who can safely receive the antibiotic at the time of testing . However, its negative predictive value for future courses is unknown because it is uncertain whether patients with a history of penicillin allergy are at risk of becoming resensitized . OBJECTIVE: To determine the rate of penicillin resensitization in adult patients with a history of penicillin allergy after they are challenged with repeated courses of oral penicillin . METHODS: Adult patients with a history of penicillin allergy consistent with an IgE-mediated mechanism were recruited and underwent penicillin skin testing . Those with negative skin test results were challenged with 3 successive 10-day courses of penicillin V potassium (250 mg by mouth 3 times a day), providing their penicillin skin test results remained negative prior to each course . Patients with positive skin test results were not challenged . RESULTS: Of 53 patients with initially negative skin test results, 46 completed the protocol, and each tolerated all 3 courses of penicillin with negative skin test results throughout . No patients had a converted skin test result from negative to a positive, yielding a resensitization rate of 0% (upper 95% confidence interval, 2.1%) . CONCLUSIONS: Adult patients with a history of penicillin allergy are not at increased risk of resensitization after receiving 3 courses of oral penicillin . Because a negative penicillin skin test result is predictive for subsequent oral administrations beyond the time of testing, adult patients with a history of penicillin allergy can be skin tested electively, which may avoid unnecessary treatment with alternate broad-spectrum antibiotics.

Przegl Epidemiol, 2001, 55(4), 511 - 5
{Borrelia burgdorferi infection in children}; Duszczyk E et al.; OBJECTIVE: The aim of our analysis of causes of borreliosis in children hospitalized or ambulatory treated in the Clinic of Infectious Disease in Childhood of Medical University in Warsaw . METHODS AND MAIN OBSERVATIONS: We observed 113 children from 6 month to 15 years old . Erythema migrans was diagnosed in 97 cases and in 3 cases was multiple erytheme migrans . RESULTS AND CONCLUSIONS: Neuroborreliosis was diagnosed in 11 children . In the treatment neuroboreliosis the ceftriaxon and cristalline penicillin was administrated.

Med J Aust, 2002 Feb 18, 176(4), 176 - 8
Howard Florey, Alexander Fleming and the fairy tale of penicillin; Goldsworthy PD et al.; The public myth of the discovery of penicillin is an archetypal "quest story" of the type common to every human culture . But the real story of the discovery, testing and refinement of penicillin is a complex tale of accident, serendipity, oversight, conflict, the pressure of war, idiosyncratic personalities and even--the invention of history.

Crit Care Med, 2002 Jan, 30(1), 77 - 82
Elevation of plasma peptidoglycan and peripheral blood neutrophil activation during hemorrhagic shock: plasma peptidoglycan reflects bacterial translocation and may affect neutrophil activation; Shimizu T et al.; OBJECTIVE: To investigate the relations among bacterial transloation, plasma peptidoglycan elevation, and peripheral blood neutrophil activation during hemorrhagic shock . DESIGN: Prospective, randomized, unblinded animal study . SETTING: Surgical research laboratories of Shiga University of Medical Science . SUBJECTS: Male, specific pathogen-free Sprague-Dawley rats . INTERVENTIONS: The rats were randomly divided into three groups: a conventional group with normal intestinal flora (NF), an antibiotic (streptomycin and penicillin G) decontaminated group (AD), and a sham shock group with normal intestinal flora . The NF and AD groups were subjected to hemorrhagic shock (mean arterial pressure 30 mm Hg, for 30 to 90 mins) . Rats were killed at 30, 60, and 90 mins after shock induction . Systemic blood and mesenteric lymph nodes (MLNs) were cultured for the determination of bacterial translocation (BT) . Systemic plasma peptidoglycan and endotoxin concentrations were measured . To evaluate peripheral blood neutrophil activation, phagocytosis and hydrogen peroxide generation were assayed by flow cytometry . MEASUREMENTS AND MAIN RESULTS: In the NF group, BT to MLNs was significantly increased from 30 mins after shock induction . Blood culture and plasma endotoxin were positive at 90 mins but there were no significant differences . Assayed plasma peptidoglycan was significantly increased at 90 mins . Phagocytosis and hydrogen peroxide generation were significantly increased . Assayed plasma peptidoglycan concentrations showed significant positive correlations with the magnitude of BT to MLNs (r2 = .54) and hydrogen peroxide generation (r2 = .22) in individual animals . Furthermore, BT and these parameters were significantly suppressed in the AD group . CONCLUSIONS: First, we concluded that assayed plasma peptidoglycan reflects BT induced by hemorrhage because the increase in assayed plasma peptidoglycan was suppressed, as was BT, by antibiotic decontamination . Second, peripheral blood neutrophil activation was also suppressed when BT was prevented . We concluded BT to be involved in neutrophil activation . Our findings suggest hydrogen peroxide generation by neutrophils to be involved in plasma peptidoglycan elevation.

Biochem Biophys Res Commun, 2002 Mar 22, 292(1), 66 - 70
Active site mutations of recombinant deacetoxycephalosporin C synthase; Lee HJ et al.; Site-directed mutagenesis of active site residues of deacetoxycephalosporin C synthase active site residues was carried out to investigate their role in catalysis . The following mutations were made and their effects on the conversion of 2-oxoglutarate and the oxidation of penicillin N or G were assessed: M180F, G299N, G300N, Y302S, Y302F/G300A, Y302E, Y302H, and N304A . The Y302S, Y302E, and Y302H mutations reduced 2-oxoglutarate conversions and abolished (<2%) penicillin G oxidation . The Y302F/G300A mutation caused partial uncoupling of penicillin G oxidation from 2-oxoglutarate conversion, but did not uncouple penicillin N oxidation from 2-oxoglutarate conversion . Met-180 is involved in binding 2-oxoglutarate, and the M180F mutation caused uncoupling of 2-oxoglutarate from penicillin oxidation . The N304A mutation apparently enhanced in vitro conversion of penicillin N but had little effect on the oxidation of penicillin G, under standard assay conditions . (C)2002 Elsevier Science (USA).

Arch Ital Biol, 2002 Jan, 140(1), 13 - 30
Time courses of aspartate and glutamate concentrations in the focus area during penicillin induced epileptiform activity in awake rats; el-Yamany NA et al.; 1 . In 16 awake rats, the time courses of cortical aspartate (ASP) and glutamate (GLU) concentrations were investigated before, during and after penicillin-induced epileptiform activity (PCN-EA) . The amino acids were collected by means of the microdialysis technique from a site within the motor cortex located close to the PCN focus . PCN-EA was recorded by means of 12 cortical electrodes . 2 . The median time courses of ASP and GLU concentrations demonstrated no relation to the time course of PCN-EA . In contrast, the analysis of individual time courses revealed three response types for both ASP and GLU which could not be related to specific sites within the motor cortex . 3 . The ASP concentration was i) not affected by epileptiform activity (8 of 16 rats), ii) changed synchronously with the PCN-EA (3 of 16), or iii) increased transiently or in a long-lasting manner during or after disappearance of PCN-EA (5 of 16) . 4 . The GLU concentration was i) not effected or only slightly affected by epileptiform activity (5 of 16), ii) decreased strongly during the activity (7 of 16), or iii) increased during the epileptiform activity (4 of 16) . 5 . If all rats were taken into account, the overall observation was absence of a uniform correlation type between the time courses of ASP and GLU concentrations; i.e . epileptiform activity affects the time courses of ASP and GLU concentrations in an independent manner . 6 . These results demonstrate that consideration of median values alone can mask significant effects of epileptiform activity on the biochemistry of the brain in individual animals . The study also shows that a consideration of individual time courses of physiological and biochemical parameters is mandatory for the understanding of basic mechanisms of epilepsy . The results support the hypothesis about the activation of neuroprotective mechanisms by epileptiform activity.

J Neurosurg, 2002 Mar, 96(3), 600 - 2
Bilateral cavernous sinus actinomycosis resulting in painful ophthalmoplegia . Case report; Ohta S et al.; The authors report the successful treatment of a 42-year-old man who suffered from recurrent painful ophthalmoplegia caused by bilateral cavernous sinus (CS) actinomycosis . A presumptive diagnosis of Tolosa-Hunt syndrome was made when he presented with left painful ophthalmoplegia . Recurrent ophthalmoplegia on the opposite side when steroid medications were tapered led to repeated imaging and a pterional craniotomy and biopsy sampling of the CS . These tests demonstrated acute inflammation and sulfur granules, which responded clinically and radiologically to parenterally administered penicillin therapy . Actinomycosis may present as a painful ophthalmoplegia with involvement of one or both CSs . Repeated imaging and possibly surgical exploration may be necessary to make a definitive diagnosis.

Clin Diagn Lab Immunol, 2002 Mar, 9(2), 482 - 4
Potential benefit of plasma exchange in treatment of severe icteric leptospirosis complicated by acute renal failure; Tse KC et al.; Leptospirosis is a common zoonosis seen worldwide, but it is rare in our locality (Hong Kong) . Clinical manifestations of leptospirosis are variable and may range from subclinical infection to fever, jaundice, hemorrhagic tendency, and fulminant hepato-renal failure . Severe hyperbilirubinemia and acute renal failure have been associated with high mortality . We report our experience with a patient who developed severe Weil's syndrome with marked conjugated hyperbilirubinemia and oliguric acute renal failure . These complications persisted despite treatment with penicillin and hemodiafiltration . Plasma exchange was instituted in view of the severe hyperbilirubinemia (970 micromol/liter) . This was followed by prompt clinical improvement, with recovery of liver and renal function . The beneficial effects of plasma exchange could be attributed to amelioration of the toxic effects of hyperbilirubinemia on hepatocyte and renal tubular cell function . We conclude that plasma exchange should be considered as an adjunctive therapy for patients with severe icteric leptospirosis complicated by acute renal failure who have not shown rapid clinical response to conventional treatment.

Neurol Neurochir Pol, 2001, 35(4 Suppl), 57 - 66
{Actual clinical and immunological problems of neurosyphilis and neurotuberculosis}; Wender M; In the past neurosyphilis and tuberculosis of the nervous system were the basic clinical problems in neurology . The decrease of the incidence rate has changed the situation . However, in the last few years, especially in connection with HIV infection, the incidence has even started to increase . In Poland the epidemiological situation is not alarming, but there exists some concern connected with the epidemic of syphilis and tuberculosis in countries near the Polish eastern border . In the laboratory diagnosis of syphilis the highest specificity and sensitivity has the TPHA test . In the therapy till now the best results are obtained with megadoses of penicillin . Early diagnosis of tuberculous meningitis, what is the decisive factor for positive results of the treatment can be obtained by PCR technique for detection of DNA genome of mycobacterium . In the treatment the method of choice is the concomitant use of four antimycobacterial drugs . However, there exists the serious problem of often observed drug resistance of mycobacterium.

Bull Exp Biol Med, 2001 Nov, 132(5), 1037 - 40
Effect of penicillin on impulse activity of medullar neurons; Lebedeva MA; Acute experiments on narcotized rats showed that intracerebral injection of penicillin increased the mean discharge rate in neurons of the bulbar respiratory center and neurons with rhythmic activity in the gigantocellular nucleus of the medulla oblongata . It also increased the number of neurons with high-frequency bursting activity . In most inspiratory neurons penicillin prolonged the discharges and increased the number of spikes in bursts . The population of inspiratory neurons became hyperactive and suppressed activity of expiratory neurons.

Bull Exp Biol Med, 2001 Nov, 132(5), 1025 - 8
Biorhythmologic aspects of seizure activity; Torshin VI et al.; Seasonal and circadian rhythms of neuronal and organism resistance to convulsive effect of strychnine and penicillin were studied in vivo on mice and rats and in vitro on cultured mouse cerebellar sections . Resistance was assessed by the latency of seizures in mice and neuronal response to convulsants in sections . In the night and morning time (0:00-9:00) seizure resistance in mice increased: it manifested in longer latency and lower mortality compared to those in the day and evening time (12:00-21:00) . Seizure resistance was minimum in autumn and maximum in winter . Neurons in cerebellar section were most resistant to the convulsive effect of penicillin in autumn and winter and least resistant in spring and summer . Circadian rhythms of cerebellar neuron resistance to convulsants were opposite, which attests to reciprocal relations between epileptogenic and antiepileptic (cerebellar) cerebral structures.

Am J Ther, 1996 Jul, 3(7), 515 - 520
Anaphylaxis and Anaphylactoid Reactions: Diagnosis and Management; Luskin AT et al.; Anaphylaxis is an acute fatal or potentially fatal hypersensitivity reaction . Anaphylaxis represent a clinical diagnosis based on history and physical examination and includes symptoms of airway obstruction, generalized skin reactions, particularly flushing, itching, urticaria, angioedema cardiovascular symptoms including hypotension and gastrointestinal symptoms . These symptoms result from the action of mast cell mediators, especially histamine and lipid mediators such as leukotrienes and platelet activating factor on shock tissue . The shock tissue includes blood vessels, mucous glands, smooth muscle, and nerve endings . Anaphylaxis follows the typical immediate hypersensitivity time course, with a reaction beginning within minutes of antigen exposure . A late-phase reaction hours after the initial reaction may occur . Mast cell mediator release can be triggered by both IgE and non--IgE-mediated factors . Therefore, anaphylaxis may be termed anaphylaxis (IgE mediated) or anaphylactoid (non--IgE mediated) . The most common IgE-mediated triggers are drugs, typically penicillin or other beta-lactam antibiotics, foods, most commonly nuts, peanuts, fish and shellfish, or hymenoptera stings . Non-IgE-mediated causes include factors causing marked complement activation such as plasma proteins or compounds which act directly on the mast cell membrane, such as vancomycin, quinolone antibiotics, or radiographic contrast media . The pathophysiology of some trigger factors, such as aspirin, remains unclear . Therapy of anaphylaxis revolves around patient education, avoidance, desensitization or pharmacologic pretreatment when agents causing anaphylaxis need to be readministered, and early recognition and prompt therapy of reactions should they occur.

Biochem Biophys Res Commun, 2002 Mar 1, 291(3), 593 - 7
Substrate specificity of penicillin acylase from Streptomyces lavendulae; Torres-Guzman R et al.; The kinetic parameters of several substrates of penicillin acylase from Streptomyces lavendulae have been determined . The enzyme hydrolyses phenoxymethyl penicillin (penicillin V) and other penicillins with aliphatic acyl-chains such as penicillin F, dihydroF, and K . The best substrate was penicillin K (octanoyl penicillin) with a k(cat)/K(m) of 165.3 mM(-1) s(-1) . The enzyme hydrolyses also chromogenic substrates as NIPOAB (2-nitro-5-phenoxyacetamido benzoic acid), NIHAB (2-nitro-5-hexanoylamido benzoic acid) or NIOAB (2-nitro-5-octanoylamido benzoic acid), however failed to hydrolyse phenylacetil penicillin (penicillin G) or NIPAB (2-nitro-5-phenylacetamido benzoic acid) and penicillins with polar substituents in the acyl moiety . These results suggest that the structure of the acyl moiety of the substrate is more determinant than the amino moiety for enzyme specificity . The enzyme was inhibited by several organic acids and the extent of inhibition changed with the hydrophobicity of the acid . The best inhibitor was octanoic acid with a K(i) of 0.8 mM . All the results, taking together, point to an active site highly hydrophobic for this penicillin acylase from Streptomyces lavendulae . (c)2002 Elsevier Science (USA).

Lancet, 2002 Feb 9, 359(9305), 474 - 80
Chloramphenicol versus benzylpenicillin and gentamicin for the treatment of severe pneumonia in children in Papua New Guinea: a randomised trial; Duke T et al.; BACKGROUND: Pneumonia is the most frequent cause of child mortality in less-developed countries . We aimed to establish whether the combination of benzylpenicillin and gentamicin or chloramphenicol would be better as first-line treatment in children with severe pneumonia in Papua New Guinea . METHODS: We did an open randomised trial in which we enrolled children aged 1 month to 5 years of age who fulfilled the WHO criteria for very severe pneumonia and who presented to hospitals in two provinces . Children were randomly assigned to receive chloramphenicol (25 mg/kg 6 hourly) or benzylpenicillin (50 mg/kg 6 hourly) plus gentamicin (7.5 mg/kg daily) by intramuscular injection . The primary outcome measure was a good or an adverse outcome . FINDINGS: 1116 children were enrolled; 559 children were treated with chloramphenicol and 557 with benzylpenicillin and gentamicin . At presentation the median haemoglobin oxygen saturation was 71% (IQR 57-77) for those allocated chloramphenicol and 69% (55-77) for those allocated penicillin and gentamicin . 147 (26%) children treated with chloramphenicol and 123 (22%) treated with penicillin and gentamicin had adverse outcomes (p=0.11) . 36 children treated with chloramphenicol and 29 treated with penicillin and gentamicin died . More children treated with chloramphenicol than penicillin and gentamicin represented with severe pneumonia within 1 month of hospital discharge (p=0.03) . INTERPRETATION: For children with severe pneumonia in less-developed countries the probability of a good outcome is similar if treated with chloramphenicol or with the combination of benzylpenicillin and gentamicin.

Vet Microbiol, 2002 Mar 22, 85(3), 285 - 92
Neospora caninum and Waddlia chondrophila strain 2032/99 in a septic stillborn calf; Henning K et al.; Characteristics of an intracellularly growing micro-organism isolated from an aborted bovine foetus are described . The organism replicated within cytoplasmic vacuoles, was resistant to penicillin and exhibited structural characteristics compatible with Waddlia chondrophila . An ELISA specific for Chlamydia spp., immunofluorescence tests using antibodies directed against Chlamydia spp . or Simkania negevensis, and PCR using Chlamydia-specific primers showed that the agent was distinct from Chlamydiae or S . negevensis . Determination of 16S and partial 23S ribosomal RNA gene sequences in combination with the PCR results and the morphological, antigenic and developmental characteristics provided evidence that the isolate 2032/99 can be classified as W . chondrophila or a closely related organism.

Arch Dermatol, 1965 Sep, 92(3), 271 - 5
Penicillin sensitivity; Palomeque FE et al.; The results obtained in this study indicate that there are various patterns of hypersensitivity to penicillin . In order to detect these variations it is suggested that two antigens, penicillin and penicilloyl-polylysine, be employed to test for both serum and skin sensitivity . Absolutely accurate predictions cannot be made from these tests, but it is felt that their use will minimize untoward reactions of the anaphylactic type in patients thus screened for penicillin allergy.

Arch Dermatol, 1965 Aug, 92(2), 200 - 4
Recent advances in the understanding of the penicillin urticarias; Jillson OF et al.; The three major groups of immunoglobulins (gamma G, gamma A, and gamma M) associated with this disease are reviewed . The presence or absence of atopic disease may account for percentage variability of gamma A because reagins (skin-sensitizing antibodies) are found in this immunoglobulin . The gamma A is the antibody usually responsible for anaphylaxis, rather than the gamma G precipitins, so stressed in the past . All three immunoglobulins may be found in serum sickness, which could account for the complex nature of this type of penicillin urticaria . The merits of the immunological tests (penicilloyl-polylysine, benzyl penicillin, hemagglutination, basophil degranulation) for the detection of penicillin sensitivity are analyzed, particularly as each applies to the various types of penicillin urticaria (serum sickness, anaphylactic, dermographic, delayed dermographic, and simple chronic urticaria and the lupus diathesis) . The penicilloyl-polylysine test is greatly overrated as a means of predicting possible anaphylaxis . The benzyl penicillin skin test properly performed is an excellent means of indicating this.

Paediatr Anaesth, 2002 Jan, 12(1), 73 - 5
Anaphylactic shock due to cefuroxime in a patient taking penicillin prophylaxis; Prosser DP et al.; We report a case of cardiovascular collapse in a homozygous sickle cell patient undergoing elective orthopaedic surgery, following the intravenous administration of cefuroxime . This patient had no known previous drug allergies . She had been taking prophylactic penicillin V on a daily basis, for 10 years and had encountered no problems . She had received cefuroxime on at least four previous occasions, for the treatment of chest infections, with no reported problems . Her serum mast cell tryptase, 1 h after the onset of anaphylaxis, was greater than 200 microg x l(-1) (normal range 10-16) . She was skin prick tested, 6 weeks after the event, to all the drugs administered during the course of the anaesthetic and reacted positively only to cefuroxime . Specific IgE levels for penicillin determinants and latex were negative (13 and 0 IU x ml(-1), respectively UniCAP Pharmacia & Upjohn).

Sao Paulo Med J, 2002 Jan 3, 120(1), 16 - 9
Sydenham's chorea--clinical and evolutive characteristics; Terreri MT et al.; CONTEXT: During the last 12 years we have observed an increase in the frequency of Sydenham's chorea in our country . We have observed that some of our patients have presented recurrence of the chorea despite regular treatment with benzathine penicillin . OBJECTIVE: The aim of our study was to evaluate clinical and evolutive characteristics of Sydenham's chorea in a group of patients followed in our Pediatric Rheumatology Unit . TYPE OF STUDY: Retrospective study . SETTING: Section of Pediatric Rheumatology - Discipline of Allergy, Clinical Immunology and Rheumatology - Department of Pediatrics - UNIFESP - EPM . PARTICIPANTS: Two hundred and ninety patients with rheumatic fever followed between 1986 and 1999 . METHODS: We reviewed the records of 290 patients with rheumatic fever followed between 1986 and 1999 . All patients were diagnosed according to the revised Jones criteria (1992) . We included 86 patients that presented Sydenham's chorea as one of the major criteria (one or more attacks) and evaluated their clinical and evolutive characteristics as well the treatment . RESULTS: Fifty-five patients were girls and 31 were boys . The mean age at onset was 9.7 years and mean follow-up period was 3.6 years . The 86 Sydenham's chorea patients presented 110 attacks of chorea . We observed isolated chorea in 35% of the patients, and 25 (29%) presented one or more recurrences . We included only 17 of the 25 patients for further analysis, with a total of 22 recurrences of which 14 were attacks of chorea, because it was not possible to precisely detect the interval between attacks in the other patients . The approximate interval between the attacks ranged from 4 to 96 months . In 71% of the patients there was no failure in the secondary prophylaxis with benzathine penicillin, which was performed every 3 weeks . CONCLUSION: Despite the regular use of secondary benzathine penicillin prophylaxis, children with rheumatic fever have a high risk of Sydenham's chorea recurrence.

Biochem Biophys Res Commun, 2002 Feb 15, 291(1), 146 - 9
Unusual signal peptide directs penicillin amidase from Escherichia coli to the Tat translocation machinery; Ignatova Z et al.; The recently described Tat protein translocation system in Escherichia coli recognizes its protein substrates by the consensus twin arginine (SRRXFLK) motif in the signal peptide . The signal sequence of E . coli pre-pro-penicillin amidase bears two arginine residues separated by one aspargine and does not resemble the Tat-targeting motif but can nevertheless target the precursor to the Tat pathway . Mutational studies have shown that the hydrophobic core region acts in synergism with the positive charged N-terminal part of the signal peptide as a Tat recognition signal and contributes to the efficient Tat targeting of the pre-pro-penicillin amidase . (c)2002 Elsevier Science (USA).

Chir Ital, 2001 Nov-Dec, 53(6), 899 - 904
{Videolaparoscopic adrenalectomy in an unusual case of adrenal mycetoma}; Chiappalone S et al.; The authors report a rare case of mycetoma of the adrenal gland . Mycetoma is a chronic, localized, non-contagious infection of cutaneous and subcutaneous tissue characterized by tumefaction, aggregates of aetiological agents (Actinomyces or true fungi) . Sometimes an unusual site (other tissues or organs) is described in the literature, but to date no cases of adrenal gland mycetoma have been reported . The treatment of choice is surgical with associated penicillin and/or antifungal drugs . In the case reported surgical treatment is performed with a laparoscopic approach . This technique constitutes the gold standard in cases of benign neoplasms of the adrenal gland and incidentalomas . This therapeutic choice is open to criticism if a malignant neoplasm is suspected.

Biotechnol Prog, 2002 Jan-Feb, 18(1), 108 - 15
Reaction equilibrium of penicillin G with amberlite LA-2 in a nonpolar organic solvent; Lee SC et al.; Studies have been made of the reactive extraction of penicillin G by Amberlite LA-2, a secondary amine, dissolved in kerosene . On the basis of the previous works about extraction equilibria of monocarboxylic acids by some secondary amines in low polar organic solvents, four equilibrium models were suggested to describe the reaction equilibrium of penicillin G in the liquid-liquid extraction system . The calculated results from the models were compared with the experimental data of 96 runs, and only two equilibrium models seemed to be probable . Ultimately, the most reasonable extraction equilibrium model was chosen through spectroscopic studies on organic solutions obtained by five specific extraction equilibrium experiments.

J Biochem (Tokyo), 2002 Feb, 131(2), 247 - 54
A new type of aminoacyltransferase from Saccharothrix sp . AS-2 favorable for the synthesis of D-amino acid-containing peptides; Sugihara A et al.; A unique enzyme with some properties favorable for the synthesis of D-amino acid-containing peptides has been purified from the culture broth of Saccharothrix sp . AS-2 . The purification steps included ammonium sulfate fractionation, chromatographies on CM-Toyopearl 650M and ProtEx Butyl, and sucrose density-gradient isoelectric focusing . The enzyme, consisting of four subunits of 56 kDa, showed its maximum transfer activity at around pH 8.2 and 35 degrees C, and had an isoelectric point of 5.8 . The enzyme yielded homooligomers from methyl esters of D-Asp(OMe), D-Met, D-Phe, D-Trp, D-Tyr, and L-Glu(OMe), but showed no hydrolytic activity toward any of the D- or L-amino acid methyl esters tested . The homooligomers were not formed from the corresponding free amino acids . The reaction of Ac-D-Phe-OMe with DL-Ala-NH(2), DL-Leu-NH(2), DL-Phe-NH(2), or DL-Trp-NH(2) was effectively catalyzed by the enzyme, both the DD- and DL-stereoisomers of the expected N-acetyldipeptide being yielded . The resulting dipeptides remained unhydrolyzed even after 48 h incubation . Also, it showed no detectable hydrolytic activity toward casein, diastereomers of diAla, diMet, and diPhe, D-/L-amino acid amides, or D-/L-amino acid p-nitroanilides, indicating that the enzyme had no peptidase activity leading to secondary hydrolysis of the growing peptide . The enzyme activity was strongly depressed by phenylmethanesulfonyl fluoride, but not by penicillin G or ampicillin, suggesting that the protein is a serine enzyme lacking penicillin-binding ability . These observations lead us to the conclusion that the enzyme from Saccharothrix sp . AS-2 characterized in this study is a new type of aminoacyltransferase with an amino acid ester as the acyl donor, and has potential utility as a catalyst for the synthesis of D-amino acid-containing peptides.

Ear Nose Throat J, 2002 Jan, 81(1), 44 - 5
An unusual case of actinomycosis; Baliga S et al.; We describe an unusual case of actinomycosis that appeared as a nasal mass . The diagnosis was established when Actinomyces viscosus was isolated from pus obtained from the right maxillary antrum by intranasal antrostomy . The patient was treated with intravenous crystalline penicillin and made an uneventful recovery within 10 days.

Curr Microbiol, 2002 Feb, 44(2), 125 - 31
Modification of the peptidoglycan of Escherichia coli in the viable but nonculturable state; Signoretto C et al.; The aim of this study was to analyse the chemical composition of peptidoglycan and the state of some of the enzymes involved in its metabolism in Escherichia coli KN126 in the viable but nonculturable (VBNC) state which is a survival strategy adopted by bacteria (including those of medical interest) when exposed to environmental stresses . When entering the VBNC state, E . coli cells miniaturised and became coccus-shaped . Analysis of peptidoglycan chemical composition, by separation in HPLC of muropeptides released by muramidase digestion of purified peptidoglycan, indicated a high degree of cross-linking, a threefold increase in unusual DAP-DAP cross-linking, an increase in muropeptides bearing covalently bound lipoprotein, and a shortening of the average length of glycan strands in comparison with dividing cells . Analysis of penicillin-binding proteins (PBPs), enzymes involved in the terminal stage of peptidoglycan assembly showed the disappearance of high-molecular-weight PBPs 1A, 1B, 2, and 3 in VBNC cells . Finally, VBNC cells displayed an autolytic capability which was far higher than that of exponentially growing cells . It is suggested that part of these alterations of peptidoglycan may be connected with the VBNC state.

Ann Allergy Asthma Immunol, 2002 Jan, 88(1), 67 - 8
Case report of an anaphylactoid reaction to arginine; Resnick DJ et al.; BACKGROUND: Arginine is an agent commonly used to evaluate adequacy of growth hormone (GH) secretion . Because arginine is a simple amino acid, it is considered safe and rarely causes adverse reactions . OBJECTIVE: To report the second anaphylactoid reaction to arginine in a child undergoing stimulation testing with arginine for assessing GH secretion . METHODS: Allergy skin testing to arginine was performed with a protocol similar to penicillin testing 4 weeks after the anaphylactoid reaction . RESULTS: Testing revealed a positive response to the arginine . CONCLUSIONS: The use of intravenous arginine as a test of GH reserve remains safe and effective, but it is prudent to have the equipment and medication available to treat an allergic reaction.

J Bacteriol, 2002 Feb, 184(4), 904 - 12
The Escherichia coli cell division protein FtsW is required to recruit its cognate transpeptidase, FtsI (PBP3), to the division site; Mercer KL et al.; The bacterial cell division protein FtsW has been suggested to perform two functions: stabilize the FtsZ cytokinetic ring, and facilitate septal peptidoglycan synthesis by the transpeptidase FtsI (penicillin-binding protein 3) . We show here that depleting Escherichia coli cells of FtsW had little effect on the abundance of FtsZ rings but abrogated recruitment of FtsI to potential division sites . Analysis of FtsW localization confirmed and extended these results; septal localization of FtsW required FtsZ, FtsA, FtsQ, and FtsL but not FtsI . Thus, FtsW is a late recruit to the division site and is essential for subsequent recruitment of its cognate transpeptidase FtsI but not for stabilization of FtsZ rings . We suggest that a primary function of FtsW homologues--which are found in almost all bacteria and appear to work in conjunction with dedicated transpeptidases involved in division, elongation, or sporulation--is to recruit their cognate transpeptidases to the correct subcellular location.

J Biol Chem, 2002 Apr 5, 277(14), 11866 - 72 Epub 2002 Jan 22.
The trans-anethole degradation pathway in an Arthrobacter sp; Shimoni E et al.; A bacterial strain (TA13) capable of utilizing t-anethole as the sole carbon source was isolated from soil . The strain was identified as Arthrobacter aurescens based on its 16 S rRNA gene sequence . Key steps of the degradation pathway of t-anethole were identified by the use of t-anethole-blocked mutants and specific inducible enzymatic activities . In addition to t-anethole, strain TA13 is capable of utilizing anisic acid, anisaldehyde, and anisic alcohol as the sole carbon source . t-Anethole-blocked mutants were obtained following mutagenesis and penicillin enrichment . Some of these blocked mutants, accumulated in the presence of t-anethole quantitative amounts of t-anethole-diol, anisic acid, and 4,6-dicarboxy-2-pyrone and traces of anisic alcohol and anisaldehyde . Enzymatic activities induced by t-anethole included: 4-methoxybenzoate O-demethylase, p-hydroxybenzoate 3-hydroxylase, and protocatechuate-4,5-dioxygenase . These findings indicate that t-anethole is metabolized to protocatechuic acid through t-anethole-diol, anisaldehyde, anisic acid, and p-hydroxybenzoic acid . The protocatechuic acid is then cleaved by protocatechuate-4,5-dioxygenase to yield 2-hydroxy-4-carboxy muconate-semialdehyde . Results from inducible uptake ability and enzymatic assays indicate that at least three regulatory units are involved in the t-anethole degradation pathway . These findings provide new routes for environmental friendly production processes of valuable aromatic chemicals via bioconversion of phenylpropenoids.

Biochem J, 2002 Feb 1, 361(Pt 3), 635 - 9
Overexpression, purification and biochemical characterization of a class A high-molecular-mass penicillin-binding protein (PBP), PBP1* and its soluble derivative from Mycobacterium tuberculosis; Bhakta S et al.; The product of the gene ponA present in cosmid MTCY21D4, one of the collection of clones representing the genome of Mycobacterium tuberculosis, has been named penicillin-binding protein 1* (PBP1*), by analogy to the previously characterized PBP1* of M . leprae . This gene has been overexpressed in Escherichia coli . His(6)-tagged PBP1* localizes to the membranes of induced E . coli cells . Its susceptibility to degradation upon proteinase K digestion of spheroplasts from E . coli expressing the protein supports the view that the majority of the protein translocates to the periplasmic side of the membrane . Recombinant PBP1* binds benzylpenicillin and several other beta-lactams, notably cefotaxime, with high affinity . Truncation of the N-terminal 64 amino acid residues results in an expressed protein present exclusively in inclusion bodies and unable to associate with the membrane . The C-terminal module encompassing amino acids 272-663 can be extracted from inclusion bodies under denaturing conditions using guanidine/HCl and refolded to give a protein fully competent in penicillin-binding . Deletion of Gly(95)-Gln(143) results in the expression of a protein, which is localized in the cytosol . The soluble derivative of PBP1* binds benzylpenicillin with the same efficiency as the full-length protein . This is the first report of a soluble derivative of a class A high-molecular-mass PBP.

J Basic Microbiol, 2001, 41(6), 351 - 62
Carbon source regulation of beta-galactosidase biosynthesis in Penicillium chrysogenum; Nagy Z et al.; Growth and beta-galactosidase activity of the penicillin producer industrial Penicillium chrysogenum NCAIM 00237 strain were examined using different carbon sources . Good growth was observed using glucose, sucrose, glycerol and galactose, while growth on lactose was substantially slower . beta-Galactosidase activity was high on lactose and very low on all the other carbon sources tested . In glucose grown cultures after exhaustion of glucose as repressing carbon source a derepressed low level of the enzyme was observed . cAMP concentration in lactose grown cultures was relatively high, in glucose grown cultures was low . Caffeine substantially decreased glucose consumption and growth but did not increase beta-galactosidase activity and did not prevent glucose repression which rules out the involvement of cAMP in the regulation of beta-galactosidase biosynthesis in Penicillium chrysogenum.

Biotechnol Bioeng, 2002 Mar 5, 77(5), 538 - 52
A morphologically structured model for penicillin production; Birol G et al.; A morphologically structured model is proposed to describe penicillin production in fed-batch cultivations . The model accounts for the effects of dissolved oxygen on cell growth and penicillin production and variations in volume fractions of abiotic and biotic phases due to biomass formation . Penicillin production is considered to occur in the subapical hyphal cell compartment and to be affected by availability of glucose and oxygen . As it stands, the model provides a wide range of applicability in terms of operating conditions . The model has been tested for various conditions and has given satisfactory results . A series of glucose feeding profiles have been considered to demonstrate the capabilities of the proposed model . It is concluded that the model may be valuable for the interpretation of experimental data collected specifically for metabolic flux analysis during fed-batch cultivation because the elements of measured specific production rates are determined from measurements of the concentrations of the components and their mass balances . The proposed model may be further used for developing control strategies and model order reduction algorithms .

J Orthop Trauma, 2002 Jan, 16(1), 12 - 7
Treatment outcome of nonclostridial gas gangrene at a Level 1 trauma center; Takahira N et al.; OBJECTIVE: To evaluate the results of treatment of nonclostridial gas gangrene at a Level 1 trauma center . DESIGN: Retrospective . SETTING: Level 1 trauma center . PATIENTS: Seven patients with nonclostridial gas gangrene were studied . The average age of all patients at the time of admission was 40.3 years (range 14 to 67 years) . RESULTS: Three of seven patients had posttraumatic infection, and the remaining four were strongly associated with underlying diseases: diabetes mellitus in three and paraplegia as the result of a spinal cord injury in two . The time of symptom onset was clearly defined in four cases, and the average interval between symptom onset and transfer to our hospitals was six days (range 2 to 10 days) . Surgical debridement was performed immediately on admission in six patients (86 percent) . A triple antibiotic regimen consisting of penicillin, gentamicin, and clindamycin was used initially in all patients . In three patients, hyperbaric oxygen therapy was also used . The overall mortality rate was 42.9 percent (three of seven patients) . In these patients, the interval from onset of symptom to transfer to our hospital was ten days in one patient, which was longer than average, and was not accurately known in the other two patients . CONCLUSION: Nonclostridial gas gangrene is extremely rare but life-threatening . The greatest pitfall for the emergency department physician is failure to suspect it clinically . Aggressive treatment, including surgical debridement and intravenous antibiotics with or without hyperbaric oxygen therapy, must be initiated immediately to minimize morbidity and mortality.

Braz J Infect Dis, 2001 Oct, 5(5), 280 - 7 Epub 2003 Feb 21.
Syphilitic meningitis in HIV-patients with meningeal syndrome: report of two cases and review; Carmo RA et al.; Few patients with symptomatic neurosyphilis present with signs and symptoms of acute meningitis . Here we report two cases of syphilitic meningitis diagnosed in HIV patients with meningeal syndrome . The first case, a 30-year-old black bisexual male, had concurrent meningeal and ocular syphilis with persistent unusually low CSF glucose levels . He responded well to 21 days of intravenous penicillin therapy . The second case was a 55-year-old female with epilepsy, depression, behavioral disorder and confusion . The diagnosis of HIV infection was made after onset of the syphilitic meningitis . She was treated with 21 days i.v . penicillin with improvement in her clinical condition . The clinical aspects of combined neurosyphilis and HIV infection, plus special features of diagnosis and treatment are discussed.

Biochem Biophys Res Commun, 2002 Jan 11, 290(1), 427 - 30
A study on the C-terminal membrane anchoring of Escherichia coli penicillin-binding protein 5; Brandenburg K et al.; Escherichia coli penicillin-binding protein 5 (PBP5) anchors to the inner membrane in a pH-dependent manner via a C-terminal amphiphilic alpha-helix . Low pH was found to enhance both levels of PBP5 membrane anchoring and levels of alpha-helicity in an aqueous PBP5 C-terminal homologue, which led to the suggestion that levels of PBP5 membrane anchoring are related to levels of PBP5 C-terminal alpha-helicity . Here we have used Fourier-transformed infrared spectroscopy (FTIR) and a peptide homologue of the PBP5 C-terminal sequence to investigate the effect of pH on the conformational behavior of this sequence at a lipid interface and on its ability to interact with lipid . Our results suggest that the membrane-anchoring mechanism of PBP5 is unlikely to involve conformational change in the protein's C-terminal region and may therefore involve conformational changes in the protein's ectomembranous domain . (c)2002 Elsevier Science.

P R Health Sci J, 2001 Sep, 20(3), 225 - 8
Treatment of tropical sprue: the work of Dr . Bailey K . Ashford examined in retrospect; Preston AM; Tropical sprue is a malabsorption syndrome that responds to treatment with folic acid and a broad-spectrum antibiotic . Eighty years ago, prior to the identification of the vitamins and the discovery of penicillin, clinical trials often consisted of best guess treatments based upon current knowledge and available technology . Dietary interventions were emerging as effective treatments for alleviation of diseases such as pellagra and beri beri . Representative of his generation of clinicians, Bailey K . Ashford, MD, one of the pivotal figures in academic medicine in Puerto Rico, carried out dietary studies in his patients with tropical sprue . This historical retrospective presents an examination of the diets used by Ashford in terms of nutrient content and comparison to current recommended dietary allowances . Results show the diets to be inadequate for sustained nutrient value and especially low in folic acid . In summary, Ashford recognized the basic causes of tropical sprue but was unable to effectively treat the syndrome due to lack of adequate resources.

Zygote, 2001 Nov, 9(4), 331 - 7
Effect of incubation temperature on in vitro maturation of porcine oocytes: nuclear maturation, fertilisation and developmental competence; Abeydeera LR et al.; The present study examined the effect of low culture temperature during in vitro maturation (IVM) of pig oocytes on their nuclear maturation, fertilisation and subsequent embryo development . In experiment 1, oocytes were cultured at 35 or 39 degrees C for 44 h in modified tissue culture medium 199 supplemented with 10 ng/ml epidermal growth factor, 0.57 mM cysteine, 75 microg/ml potassium penicillin G, 50 microg/ml streptomycin sulphate, 0.5 microg/ml LH and 0.5 microg/ml FSH to examine the nuclear maturation status . In experiment 2, oocytes were cultured at 35 degrees C for 44 or 68 h and nuclear maturation was examined . In experiment 3, oocytes matured for 44 or 68 h at 39 degrees C and for 68 h at 35 degrees C were co-incubated with frozen-thawed spermatozoa for 5-6 h . Putative embryos were transferred into North Carolina State University (NCSU) 23 medium containing 0.4% bovine serum albumin . At 12 h after insemination, some oocytes were fixed to examine the fertilisation rate and the remaining embryos were examined at 48 and 144 h for cleavage and blastocyst formation rate, respectively . Compared with 39 degrees C, culture of oocytes at 35 degrees C for 44 h significantly (p < 0.05) reduced the metaphase II (M II) rate (79% vs 12%) . However, extension of culture time to 68 h at 35 degrees C significantly increased (p < 0.05) the M II rate (7% vs 58%) . In experiment 3, compared with other groups, fewer (p < 0.05) oocytes reached M II when cultured at 35 degrees C for 68 h (69-81% vs 49%) . Extension of culture duration to 68 h at 39 degrees C stimulated spontaneous activation (28%) of oocytes . No difference in cleavage rates was observed among different groups . Compared with oocytes matured for 44 h at 39 degrees C (31%), the proportion of blastocysts obtained was low (p < 0.05) for oocytes matured at 35 degrees C (13%) or 39 degrees C (3%) for 68 h . The results indicate that lower culture temperature can delay nuclear maturation of pig oocytes . However, extension of culture time can stimulate nuclear maturation and these oocytes are capable of fertilisation and development to the blastocyst stage at moderate rates.

Int Microbiol, 2001 Jun, 4(2), 89 - 92
Production of phenolics by immobilized cells of the lichen Pseudevernia furfuracea: the role of epiphytic bacteria; Blanch M et al.; Immobilized lichen cells from the thalli of the lichen Pseudevernia furfuracea, supplied with acetate as the only source of carbon, continuously produced phenolic substances, atranorin and physodic acid, over 23 days . Epiphytic bacteria associated with the lichen thallus grew actively, probably using both acetate and reduced compounds supplied by lichen cells, since their active growth was avoided by including 10 microM 3,3'-dichlorophenyl-1,1'dimethylurea in the bath solution . Penicillin largely impeded the growth of epiphytic bacteria and decreased phenolic production, which was recovered only at the end of the experimental period, just when the bacteria started a slow, but active growth . We suggest the cooperation of epiphytic bacteria in the biosynthesis of both atranotrin and physodic acid.

Singapore Med J, 2001 Aug, 42(8), 346 - 50
A ten-year retrospective study of tetanus at a general hospital in Malaysia; Lau LG et al.; AIMS: To study the demographic and clinical features as well as outcomes of tetanus patients at the Sarawak General Hospital, Kuching from 1990 to 1999 . METHODS: All cases of tetanus from January 1990 to September 1999 were identified from the computer record at the hospital and these were then restrospectively reviewed . RESULTS: A total of 22 cases of tetanus was seen at the Sarawak General Hospital in the ten-year period with a mean of 2.2 cases per year . There were 15 male (68.2%) and 7 female (31.8%) patients . Most cases occurred in the age group 60-69 . Eighteen patients (81.8%) had a reasonably identifiable injury prior to the onset; all had their wounds debrided . Body stiffness, trismus and dysphagia were the three commonest presenting complaints . Twenty-one patients (95.5%) were admitted to the intensive care unit (ICU), with an average length of ICU stay of 21.4 days . Nineteen patients (86.4%) required mechanical ventilation for a varying period of time in the ICU . All patients (100%) had tracheostomy performed and intravenous diazepam infusion as part of their management . Twenty patients (90.9%) received intravenous crystalline penicillin as the treatment antibiotics . Twenty-one patients (95.5%) received intramuscular human antitetanus immunoglobulin . There were four deaths, accounting for a mortality of 18.2% . CONCLUSION: In general, tetanus remains in Sarawak an important disease with substantial mortality and morbidity that primarily affects unvaccinated or inadequately vaccinated individuals . It is, however, highly preventable through both routine vaccination and appropriate wound management . Our case series show comparable pattern and outcome with other case series reported in the literatures.

Zhonghua Yi Shi Za Zhi, 2001 Jul, 31(3), 184 - 8
{The manufacturing of penicillin in China in 1940s}; Niu Y; A small modernized factory was established in early 1947, and developed into industrialized production . The manufacture of penicillin in China in the 1940s lay down the foundation for the industrialized production of penicillin in China which occupies an important position in the medical history of China.

Zhonghua Fu Chan Ke Za Zhi, 2001 Aug, 36(8), 460 - 1
{Treatment of syphilis in pregnancy and its perinatal prognosis}; Xu Y et al.; OBJECTIVE: To investigate the effects of treatment of syphilis in pregnancy on perinatal prognosis . METHODS: Patients of syphilis in pregnancy from Hainan Provincial People's Hospital and Haikou Municipal Maternal and Child Health Center during 1995.1 to 2001.1 were collected for retrospective analysis . Pregnant women with syphilis were divided into treated group and untreated group according to whether they received penicillin anti-syphilis treatment or not during pregnancy . RESULTS: The total number of deliveries in the 2 hospitals during that period was 18,701, and 61 out of 9,805 women screened for syphilis were positive, giving an incidence of 6.2/1000 . The perinatal mortality rates were 11.2% in treated group and 83.3% in untreated group, and incidences of congenital syphilis were 17.6% and 72.7% respectively . CONCLUSION: Syphilis in pregnancy is a serious complication to harm the fetus . Screening of syphilis during pregnancy is necessary, and penicillin treatment is effective which may reduce the perinatal mortality rate and the birth of congenital syphilis baby.

Zhonghua Fu Chan Ke Za Zhi, 2001 Aug, 36(8), 456 - 9
{Syphilis in pregnancy women}; Lu J et al.; OBJECTIVE: To investigate obstetric treatment and pregnancy outcomes of syphilis infection during pregnancy . METHODS: 64 pregnant women diagnosed with syphilis by serological assays were divided into treated group and untreated group according to whether they accepted full-dose treatment against syphilis or not . Patients in the treated group accepted benzathine penicillin(2.4 million units once per week) intramuscular injection for three weeks . The outcome of pregnan after treatment was observed and compared between the two groups . RESULTS: There were 5 cases of primary syphilis (7.8%), 29 cases of secondary syphilis (45.3%), and 30 cases of latent syphilis (46.9%) among the 64 cases . The occurrences of premature birth, fetal intrauterine death, and stillbirth were 0, and 3 cases of congenital syphilis in total 13 cases who carried pregnancy to term in the treated group; while 4, 11, 3, and 10 in the untreated group respectively . In treated group, the 3 babies with congenital syphilis were born from 10 mothers received treatment after 24 gestational weeks, while no congenital syphilis in the 3 women started treatment before 24 weeks . CONCLUSIONS: Pregnant syphilis is prone to be misdiagnosed because of its slight symptom, so it is especially important to screen syphilis as a routine among high risk pregnant women . Premature, fetal death and congenital syphilis can be well controlled through regular and early treatment during pregnancy, yet congenital syphilis can not be avoided completely.

Pediatr Emerg Care, 2001 Dec, 17(6), 425 - 9
Systemic cytokine response in children bitten by snakes in Costa Rica; Avila-Aguero ML et al.; BACKGROUND: To characterize the host response to venom from snakes of the family Viperidae in Costa Rica, we investigated the release of cytokines: IL-1, IL-6, IL-8, TNF-alpha, MIP-1beta, and RANTES in pediatric patients who were bitten by a snake . METHODS: Patients were included in this study if they were admitted to the hospital within 24 hours of the snakebite . Blood samples were taken immediately on admission to the hospital, and then at intervals of 3, 12, and 24 hours, and on days 3, 5, and 7 after the accident . Patients received gentamicin plus clindamycin or gentamicin plus penicillin intravenously for a minimum of 3 days or longer if necessary . IL-1, IL-8, TNF-alpha, MIP-1beta, and RANTES were determined by monoclonal antibody-based ELISAs, while IL-6 was determined by bioassay . RESULTS: Eighteen patients were included in this study; 15 were bitten by Bothrops asper and three by B . lateralis . Eleven patients were male . Median (range) age was 9 (1-12) years . Nine patients had detectable serum concentrations of IL-6 (200 pg/ mL) and IL-8 (51 pg/mL) on admission, increasing to 500 pg/mL and 115 pg/mL for IL-6 and IL-8, respectively, during the first 12-24 hours . Cytokine concentrations returned to normal or undetectable ranges by 72 hours . TNF-alpha concentrations peaked at 12 hours (mean: 48 pg/mL) . Low, but detectable concentrations of MIP-1beta were observed in some patients at various time intervals (48 pg/mL), whereas IL-1 was not detectable at any time point . Regulated on Activation Normal T cell Expressed and Secreted (RANTES) concentrations were evaluated in only five patients, being elevated in all of them . Patients with elevated cytokine concentrations required early fasciotomy (<24 hours after the accident) more often than those who had normal or undetectable cytokine concentrations (P < 0.05) . There were no statistically significant associations between severity of envenomation, or outcome, and elevated serum cytokine concentrations (P > 0.05) . CONCLUSIONS: Bothrops sp snake venoms induce clinical and pathophysiologic alterations similar to acute trauma, with release of proinflammatory cytokines . A better understanding of the role of the inflammatory response could lead to the development of new therapeutic strategies to improve the outcome in snakebitten patients.

Antimicrob Agents Chemother, 2002 Jan, 46(1), 188 - 90
Gentamicin increases the efficacy of vancomycin against penicillin-resistant pneumococci in the rabbit meningitis model; Cottagnoud P et al.; In experimental meningitis a single dose of gentamicin (10 mg/kg of body weight) led to gentamicin levels in around cerebrospinal fluid (CSF) of 4 mg/liter for 4 h, decreasing slowly to 2 mg/liter 4 h later . The CSF penetration of gentamicin ranged around 27%, calculated by comparison of areas under the curve (AUC in serum/AUC in CSF) . Gentamicin monotherapy (-1.24 log(10) CFU/ml) was inferior to vancomycin monotherapy (-2.54 log(10) CFU/ml) over 8 h against penicillin-resistant pneumococci . However, the combination of vancomycin with gentamicin was significantly superior (-4.48 log(10) CFU/ml) compared to either monotherapy alone . The synergistic activity of vancomycin combined with gentamicin was also demonstrated in vitro in time-kill assays.

Acta Pharmacol Sin, 2001 Nov, 22(11), 986 - 90
Inhibitory effect of jujuboside A on penicillin sodium induced hyperactivity in rat hippocampal CA1 area in vitro; Shou CH et al.; AIM: To study the effect of jujuboside A (JuA), one constituent of Chinese herbal medicine Ziziphus jujuba Mill Var spinosa (Bunge) Hu,on the penicillin sodium induced hyperactivity in rat CA1 neurons in vitro . METHODS: Hippocampal slices were obtained from the Sprague-Dawley rat brain and populational signals were measured from CA1 neurons of hippocampal slices using the extracellular recording technique . RESULTS: Penicillin sodium of 500, 1000, and 2000 kU/L were found to excite hippocampal CA1 neurons in a concentration-dependent manner in vitro . This excitatory effect of penicillin sodium could be inhibited by phenobarbital sodium of 0.02 - 0.05 g/L and JuA of 0.05 - 0.10 g/L . CONCLUSION: A high dose of JuA can inhibit the hyperactivity of hippocampal CA1 area induced by penicillin sodium . The inhibition of the amplitude of the first population spike (PS) and the latency of PS are more pronounced than the slope of the field excitatory post-synaptic potential.

Biotechnol Bioeng, 2001 Dec, 76(4), 311 - 7
A novel enzyme reactor using gluten membrane entrapping cell-associated enzyme; Lee WC et al.; A membrane enzyme reactor consisting of variable pieces of replaceable cell-immobilized membranes was proposed for the continuous production of bioproducts . To demonstrate the characteristics of the reactor, cell-immobilized membranes were prepared by the entrapment of permeabilized recombinant Escherichia coli cells containing penicillin G acylase within the gluten matrices . A stainless-steel net that was created with a mesh frame was used to support each gluten membrane so that the membranes could be filled into the rectangular-shaped reactor . The reactor equipped with either six or 12 pieces of cell-immobilized gluten membranes containing a biomass concentration of 5%, w/w was effective in catalyzing the production of 6-aminopenicillanic acid from penicillin G . In comparison with intact cells, the cell-immobilized preparation was more stable and the half-life time of the immobilized cell-associate enzyme in gluten membrane was estimated to be 36 days by a long-term operation . As the substrate solution was forced to flow through the reactor equipped with six membranes and in the direction perpendicular to the membranes, the pressure drop was determined to be less than 50 cm H(2)O with a flow-rate up to 50 mL/min . This low pressure due to the porous structure of gluten membrane would lead to a lower operational cost . Increasing either the number of membranes or the area of each cell-immobilized membrane can easily do scaling-up of this membrane reactor .

Acta Anaesthesiol Scand, 2001 Nov, 45(10), 1204 - 9
Danish Anaesthesia Allergy Centre - preliminary results; Garvey LH et al.; BACKGROUND: Anaphylactoid reactions in anaesthesia are rare and should ideally be investigated in specialist centres . At Gentofte University Hospital, we established such a centre in 1998 as a joint venture between the Departments of Anaesthesiology and Dermatology . We present the methodology, diagnostic algorithm and preliminary results from our centre . METHODS: We are open for referral of patients from all of Denmark . Reactions are classified using a three-grade severity scale and all reactions ranging from mild to severe are investigated . Investigations follow a standard step-by-step protocol of in vitro testing and skin testing . Blood samples for tryptase analysis are taken at the time of reaction and a control sample is taken together with samples for specific IgE analysis 2-4 weeks after the reaction . Subsequent skin testing comprises both prick tests and intradermal tests in most cases . Patients are tested with all substances they were exposed to, including antibiotics, colloids, latex and chlorhexidine . RESULTS: A total of 68 patients have been referred to date (July 2001) and 36 have completed investigations . Positive test results were mainly seen in patients with more severe reactions, and there were more men than women in the group with the most severe reactions . Six patients had positive specific IgE, three for penicillin, two for latex and one for thiopental . In all, 21 patients had positive skin tests to various substances, of whom four men with anaphylactic shock tested positive for chlorhexidine . Only one patient has tested positive to a neuromuscular blocking drug (NMBD) so far . DISCUSSION: Our preliminary results appear to differ in two ways from results usually found in this field . Firstly, only one patient has tested positive for a NMBD and secondly, we have had four patients with anaphylactic shock who have tested positive for chlorhexidine . Possible reasons for these differences are discussed.

Pediatr Infect Dis J, 2001 Sep, 20(9), 901 - 3
Abdominal actinomycosis with hydronephrosis in childhood; Campo JM et al.; Two 11-year-old boys had similar clinical courses of abdominal actinomycosis complicating ruptured appendicitis and manifesting as abdominal masses causing hydronephrosis . Cure was effected by surgery and prolonged penicillin therapy.

Curr Opin Ophthalmol, 2001 Dec, 12(6), 433 - 41
Ocular syphilis; Aldave AJ et al.; Although the annual incidence of primary and secondary syphilis has dropped to the lowest rate recorded, syphilis remains an important cause of ocular disease . Uveitis is the most common ocular manifestation of syphilis in both HIV-positive and HIV-negative patients, and the diagnosis should prompt an analysis of the cerebrospinal fluid to exclude associated neurosyphilis . Newer modalities such as enzyme immunoassays and genomic amplification using the polymerase chain reaction may prove to be useful techniques to detect Treponema pallidum in intraocular specimens . The preferred treatment for all stages of syphilis remains parenteral penicillin G, although the preparation, dose, route of administration, and duration of therapy are dictated by the stage of disease and various host factors . All patients diagnosed with ocular syphilis should be tested for HIV, because the presence of a primary genital chancre increases the risk of acquiring or transmitting HIV, and because risk factors for the two diseases are similar.

Cardiol Young, 2001 Sep, 11(5), 556 - 8
Tricuspid valvar endocarditis caused by penicillin resistant pneumococcus; Bothwell JE et al.; A 6-year-old boy presented with endocarditis of the tricuspid valve caused by penicillin resistant pneumococcus . He had no history of congenital cardiac disease . The likely portal of entry for the organism was the middle ear.

Ann Pharmacother, 2001 Nov, 35(11), 1360 - 3
Stability of piperacillin and ticarcillin in AutoDose infusion system bags; Zhang Y et al.; OBJECTIVE: To evaluate the physical and chemical stability of piperacillin sodium 3 and 4 g/100 mL and ticarcillin disodium 3 g/100 mL each admixed in NaCl 0.9% injection packaged in AutoDose Infusion System bags . DESIGN: Triplicate test samples of the penicillin antibiotics in NaCl 0.9% injection were packaged in ethylene vinyl acetate (EVA) plastic containers, AutoDose bags, designed for use in the AutoDose Infusion System . Samples were stored protected from light and evaluated at appropriate intervals for up to seven days at 23 degrees C and up to 30 days at 4 degrees C . Physical stability was assessed using turbidimetric and particulate measurement as well as visual inspection . Chemical stability was assessed by HPLC . RESULTS: All of the penicillin admixtures initially were clear when viewed in normal fluorescent room light and with a Tyndall beam . Measured turbidity and particulate content were low initially and exhibited little change in the ticarcillin disodium samples throughout the study . The piperacillin sodium samples exhibited small increases in measured haze throughout the study, but no accompanying increase in particulates > or = 1.04 microm was found . All samples were essentially colorless throughout the study . HPLC analysis found some decomposition in the samples . Piperacillin sodium exhibited a 9-10% loss after five days at 23 degrees C . In the samples stored at 4 degrees C, piperacillin sodium exhibited acceptable stability through 21 days of storage, but losses exceeded 10% after 30 days . Ticarcillin disodium exhibited a 7% loss after three days, but 14% after five days at 23 degrees C . Less than 7% loss occurred after 21 days, but 12% loss after 30 days at 4 degrees C . CONCLUSIONS: Piperacillin sodium and ticarcillin disodium exhibited physical and chemical stability consistent with previous studies on these drugs . The AutoDose Infusion System bags were not found to adversely affect the physical and chemical stability of these penicillin antibiotics.

Am J Gastroenterol, 2001 Nov, 96(11), 3195 - 8
Mushroom poisoning--from diarrhea to liver transplantation; Broussard CN et al.; Mushroom poisoning from the genus Amanita is a medical emergency, with Amanita phalloides being the most common species . The typical symptoms of nausea, vomiting, abdominal pain, and diarrhea are nonspecific and can be mistaken for gastroenteritis . If not adequately treated, hepatic and renal failure may ensue within several days of ingestion . In this case series, patients poisoned with Amanita virosa are described with a spectrum of clinical presentations and outcomes ranging from complete recovery to fulminant hepatic failure . Although there are no controlled clinical trials, a few anecdotal studies provide the basis for regimens recommended to treat Amanita poisoning . Use of i.v . penicillin G is supported by most reports . Silibinin, although preferred over penicillin, is not easily available in the United States . In those with acute liver failure, liver transplantation can be life saving.

Biomacromolecules, 2000 Winter, 1(4), 739 - 45
Multifunctional epoxy supports: a new tool to improve the covalent immobilization of proteins . The promotion of physical adsorptions of proteins on the supports before their covalent linkage; Mateo C et al.; Multifunctional supports containing epoxy groups are here proposed as a second generation of activated supports for covalent immobilization of enzymes following the epoxy chemistry on any type of support (hydrophobic or hydrophilic ones) under very mild experimental conditions (e.g., low ionic strength, neutral pH values, and low temperatures) . These multifunctional supports have been easily prepared by modifying a small fraction (10-20%) of the epoxy groups contained in commercial epoxy supports . In this way, additional groups that were able to physically adsorb proteins (e.g., cationic or anionic groups, metal chelate, phenyl boronate) are generated on the support surface . The covalent immobilization of proteins on these supports proceeds via their initial physical adsorption on the supports (via different structural features) . Then, "intramolecular" covalent linkages between some nucleophilic groups of the adsorbed enzyme (e.g., amino, thiol, or hydroxy groups) and the dense layer of nearby epoxy groups on the support are established . This two-step covalent immobilization dramatically improves the very low reactivity of epoxy groups toward nonadsorbed proteins . In this way, all other relevant practical advantages of epoxy groups for protein immobilization (their high stability and their ability to form very strong linkages with several nucleophilic enzyme residues with minimal chemical modification) can be an object of universal exploitation . The use of these new multifunctional supports exhibits important advantages regarding immobilization of enzymes previously adsorbed on hydrophobic homofunctional epoxy supports: (i) hydrophilic supports can also be used for immobilization of industrial enzymes; (ii) immobilization can also be carried out at low ionic strength; (iii) every protein contained in crude extracts from Escherichia coli and Acetobacter turbidans can be immobilized by sequentially using a set of different supports; (iv) in most cases, each enzyme has been immobilized on different supports, orientated through different structural features and very likely involving different areas of its surface . For example, three industrial enzymes (penicillin G acylase, lipase, and beta-galactosidase) could be immobilized through different strategies yielding immobilized derivatives with very different activities . The best derivatives preserved 75-100% of activity corresponding to the soluble enzymes used for immobilization, while in some cases a particular immobilization protocol promoted the full inactivation of the enzyme.

Antimicrob Agents Chemother, 2001 Dec, 45(12), 3509 - 16
Characterization of OXA-29 from Legionella (Fluoribacter) gormanii: molecular class D beta-lactamase with unusual properties; Franceschini N et al.; A class D beta-lactamase determinant was isolated from the genome of Legionella (Fluoribacter) gormanii ATCC 33297(T) . The enzyme, named OXA-29, is quite divergent from other class D beta-lactamases, being more similar (33 to 43% amino acid identity) to those of groups III (OXA-1) and IV (OXA-9, OXA-12, OXA-18, and OXA-22) than to other class D enzymes (21 to 24% sequence identity) . Phylogenetic analysis confirmed the closer ancestry of OXA-29 with members of the former groups . The OXA-29 enzyme was purified from an Escherichia coli strain overexpressing the gene via a T7-based expression system by a single ion-exchange chromatography step on S-Sepharose . The mature enzyme consists of a 28.5-kDa polypeptide and exhibits an isoelectric pH of >9 . Analysis of the kinetic parameters of OXA-29 revealed efficient activity (k(cat)/K(m) ratios of >10(5) M(-1) x s(-1)) for several penam compounds (oxacillin, methicillin, penicillin G, ampicillin, carbenicillin, and piperacillin) and also for cefazolin and nitrocefin . Oxyimino cephalosporins and aztreonam were also hydrolyzed, although less efficiently (k(cat)/K(m) ratios of around 10(3) M(-1) x s(-1)) . Carbapenems were neither hydrolyzed nor inhibitory . OXA-29 was inhibited by BRL 42715 (50% inhibitory concentration {IC(50)}, 0.44 microM) and by tazobactam (IC(50), 3.2 microM), but not by clavulanate . It was also unusually resistant to chloride ions (IC(50), >100 mM) . Unlike OXA-10, OXA-29 was apparently found as a dimer both in diluted solutions and in the presence of EDTA . Its activity was either unaffected or inhibited by divalent cations . OXA-29 is a new class D beta-lactamase that exhibits some unusual properties likely reflecting original structural and mechanistic features.

Klin Monatsbl Augenheilkd, 2001 Oct, 218(10), 691 - 4
{Optic nerve involvement in syphilis in 4 patients}; Freigassner PS et al.; BACKGROUND: Due to increasing numbers of cases syphilis again becomes more important in ophthalmology . Syphilitic ocular manifestations do not show any typical characteristics and therefore are often not diagnosed although a correct and early diagnosis with adequate therapy is very important for the visual outcome . PATIENTS: We report on four patients with luetic ocular fundus manifestations, who were referred to our clinic with unspecific ocular complaints . Funduscopic examination revealed in all patients a papilledema, which was bilateral in three patients and unilateral in one patient . Additional findings were a non-granulomatous uveitis anterior and a chorioretinitis in both eyes of a 61-year-old HIV positive patient with retinal scars from a bilateral acute retinal necrosis syndrome (ARN), a mild non granulomatous iridocyclitis in a 53-year-old patient and a bilateral chorioretinitis and a cystoid macular edema in a 37-year-old patient . A 54-year-old patient showed a vein branch occlusion . Serological analysis demonstrated active syphilis in all cases and an EBV-infection in two patients . After penicillin therapy the ocular findings resolved . CONCLUSION: In all cases of inflammatory fundus manifestations syphilis should be taken into consideration and serological lues tests should be performed routinely.

Biochem Biophys Res Commun, 2001 Nov 16, 288(5), 1175 - 81
Penicillin conjugates to interferon-gamma and reduces its activity: a novel drug-cytokine interaction; Brooks BM et al.; Beta-lactam antibiotics are the class of drug most frequently associated with IgE-mediated allergy but the mechanisms underlying this response are poorly understood . IFN-gamma is a key cytokine in immunity with regulatory actions on monocytes, NK cells, epithelial cells, and T and B lymphocytes . IFN-gamma promotes Th1 responses and inhibits Th2- and IgE-mediated responses . In this study we show, by Western blotting, that the prototype beta-lactam benzylpenicillin (BP) conjugates to human IFN-gamma but not to IL-4 . The interaction of BP with IFN-gamma inhibited the cytokine's detection by immunoassay and impaired its activity, as assessed in three different assays: upregulation of MHC molecules on monocytes plus induction of nitric oxide synthesis and expression of monocyte chemoattractant protein-1 mRNA by epithelial cells . This is the first reported example of a direct drug-cytokine interaction and suggests a mechanism by which penicillin may disrupt IFN-gamma-dependent immune responses and promote allergy .

Ther Umsch, 2001 Oct, 58(10), 588 - 91
{Pneumococcal pneumonia}; Trampuz A et al.; Pneumococci remain the most important cause of bacterial pneumonia with a considerable morbidity and mortality . The characteristic features of pneumococcal pneumonia are fever, shivering, productive cough, and radiographic detection of an infiltrate . Penicillin is still the cornerstone of therapy for pneumococcal infections . With the HIV-epidemic and worldwide emergence of resistant strains particularly the invasive pneumococcal infections became a growing therapeutic problem.

J Biochem Biophys Methods, 2001 Oct 30, 49(1-3), 553 - 60
Penicillin acylase purification with the aid of pseudo-affinity chromatography; Fitton V et al.; The introduction of affinity chromatography has opened a new dimension in protein purification . This article reviews the current techniques used in the penicillin acylase purification process, especially pseudo-affinity chromatography . A profile for a suitable ligand is established . An aromatic ring and the presence of one or several amino groups seem essential for proper interaction . Immobilized metal affinity chromatography now seems to be a good competitor.

Neurosci Behav Physiol, 2001 Sep-Oct, 31(5), 497 - 501
Structural bases of intracortical processes underlying the synchronization of epileptic potentials in the sensorimotor areas of the neocortex in rats; Pasikova NV et al.; Studies in long-term isolated areas of the rat neocortex were performed to investigate the dynamics of the numbers and areas of nerve cell bodies in layer V and to compare these data with the degree of synchronization of epileptic discharges evoked by application of penicillin . Decreases in the number of pyramidal neurons with body areas of 200-350 microm2 in isolated strips after maintenance for 30 and 90 days led to decreases in the degree of synchronization of epileptiform potentials . Large pyramidal neurons are known to have long horizontal axon collaterals, spreading into layers V and VI of the neocortex . It is suggested that the neural networks formed by large pyramidal neurons by means of their long horizontal collaterals mediate the process of intracortical synchronization.

Curr Microbiol, 2001 Oct, 43(4), 265 - 70
Isolation and partial characterization of Het- Fix- mutant strain of the diazotrophic cyanobacterium Anabaena variabilis showing chromatic adaptation; Singh B et al.; We propose a model to describe the changes taking place in biochemical processes/events to explain the development of heterocyst and nitrogenase in a diazotrophic cyanobacterium Anabaena variabilis . For this purpose, a mutant strain of A . variabilis lacking heterocyst differentiation and incapable of growth with dinitrogen as the sole source of nitrogen has been isolated after nitrosoguanidine (NTG) mutagenesis and selection by penicillin enrichment . The mutant strain (Het- Fix-) thus isolated has morphological variation and was incapable of reducing acetylene under anaerobic conditions, indicating its mutational loss of the process of nitrogen fixation . The Het- Fix- mutant strain had reduced glutamine synthetase (transferase) activity compared with its wild-type counterpart, suggesting a link between nif gene expression and the expression of gln A, the structural gene of GS . The Het- Fix- mutant strain compared with its wild-type strain also had an extremely high level of phycobiliprotein and a low level of carotenoids . Furthermore, the coiling of vegetative filaments in the Het- Fix- mutant strain, which reduced the surface area to be exposed to light, was a direct indication of the chromatic adaptation, because the mutant strain was found to be photosensitive, showing bleaching of the cells under high light intensity.

Euro Surveill, 2001 Jan, 6(1), 2 - 5
EARSS activities and results: update; Bronzwaer SL et al.; (And with EARSS participants) The latest EARSS results (1990-2000) suggest that the rates of methicillin resistant S . aureus and Penicillin Non Susceptible S . pneumoniae are higher in southern European countries than in the North . Young children, followed by elderly people are the most at risk for an infection by PNSP . The risk to be infected by methicillin resistant S . aureus increases with age, patients hospitalised in intensive care units being more exposed to that risk.

Rinsho Biseibutshu Jinsoku Shindan Kenkyukai Shi, 2001, 12(1), 9 - 13
{Evaluation of MRSA identification with latex agglutination kit for the detection of penicillin-binding protein 2}; Ito Y et al.; MRSA is one of the major nosocomial pathogens, and methicillin-resistance is associated with acquisition of the mecA gene coding for the penicillin-binding protein 2' (PBP2') . MRSA-screen test (Denka Seiken Co., Ltd., Tokyo, Japan) is a slide latex agglutination kit which can detect PBP2' within 15 min . MRSA-screen test was compared with PCR for detection of the mecA gene in order to detect MRSA . S . aureus strains isolated from April to October in 1999 in Gifu Red Cross Hospital were identified as 25 MRSA and 19 MSSA by susceptibility testing to oxacillin by the agar dilution method according to the recommendation of the National Comittee for the Clinical Laboratory Standards . The MRSA screen test and PCR for the mecA gene showed sensitivites of 92.0 and 96.0% and specificities of 89.5 and 94.7%, respectively . It is considered that MRSA-screen is a rapid and reliable test for discrimination of MRSA from MSSA colonies on agar plates.

J Org Chem, 1999 Feb 5, 64(3), 713 - 720
Synthesis and Reactivity with beta-Lactamases of "Penicillin-like" Cyclic Depsipeptides; Cabaret D et al.; Several 7-carboxy-3-amido-3,4-dihydro-2H-1-benzopyran-2-ones have been synthesized as potential beta-lactamase substrates and/or mechanism-based inhibitors . Substituted o-tyrosine precursors were prepared by the Sorensen method and then heated in vacuo to give the lactones . These compounds are cyclic analogues of aryl phenaceturates which are known to be beta-lactamase substrates . The goal of incorporating the scissile ester group into a lactone was to retain the leaving group tethered to the acyl moiety at the acyl-enzyme stage of turnover by serine beta-lactamases, in a manner similar to that during penicillin turnover . Further, in two cases, a functionalized methylene group para to the leaving group phenoxide oxygen was incorporated . These molecules possess a latent p-quinone methide electrophile which could, in principle, be unmasked during enzymic turnover and react with an active site nucleophile . All of these compounds were found to be substrates of class A and C beta-lactamases, the first delta-lactones with such activity . Generally, k(cat) values were smaller than for the analogous acyclic depsipeptides, which suggests that the tethered leaving group may obstruct the attack of water on the acyl-enzymes . Further exploration of this structural theme might lead to quite inert acyl-enzymes and thus to significant inhibitors . Despite the apparent advantage offered by the longer-lived acyl-enzymes, the functionalized compounds were no better as irreversible inhibitors than comparable acyclic compounds {Cabaret, D.; Liu, J.; Wakselman, M.; Pratt, R . F.; Xu, Y . Bioorg . Med . Chem . 1994, 2, 757-771} . Thus, even tethered quinone methides, at least when placed as dictated by the structures of the present compounds, were unable to efficiently trap a nucleophile at serine beta-lactamase active sites.

Electrophoresis, 2001 Oct, 22(16), 3573 - 7
The effect of a functional group in penicillin derivatives on the interaction with bile salt micelles studied by micellar electrokinetic chromatography; Mrestani Y et al.; A capillary electrophoresis method is developed and validated for the characterization of the affinity and the interaction between aminopenicillanic acid (APS-H) and its derivatives with bile salt micelles . The micellar systems studied contained sodium taurocholate (NaTC) and sodium deoxycholate (NaDC) . Using the retention factor k', functional group selectivity, gammaG, is defined as the ratio of the retention factor of a substituted aminopenicillanic acid (APS-R) over the capacity factor of APS-H and the difference in free energy (deltadeltaG degrees) can be used for the characterization of the affinity and interaction between drugs and micelles . The functional group selectivity is a direct measure of the interaction of the functional group with micelles . The calculated deltadeltaG degrees value gives information on the partition equilibrium and interaction between drugs and micelles . A positive deltadeltaG degrees value means that the interaction of a functional group gammaG to the APS-H leads to a decrease in the interaction with the micelles . A negative deltadeltaG degrees value, on the other hand, has the opposite meaning . The results obtained in this study exhibited that these APS-R compounds have smaller affinity to the micelles compared to unsubstituted APS-H . Furthermore, the log k' of the drugs in these systems were correlated with the log Pow in the n-octanol/water system and with log P(G) (permeation coefficient).

Scand J Infect Dis, 2001, 33(9), 706 - 8
Recurrent Pneumococcal bacteraemia and meningitis in an asplenic adult with possible unusual focus; Kragsbjerg P et al.; An unusual case of a dental infection leading to osteitis of the mandible and possibly to 4 episodes of invasive pneumococcal disease in an asplenic adult is presented . The patient had 2 episodes of pneumococcal meningitis with bacteraemia and 2 episodes of bacteraemia without meningitis during a 1-y period . Investigations using bone and leukocyte scintigraphy revealed only a focal uptake in the right mandibular bone . The pneumococcal strains isolated during the 4 episodes were all serotype 23F, and fully susceptible to penicillin.

J Org Chem, 1996 Dec 13, 61(25), 8975 - 8979
Penicillin Acylase-Mediated Synthesis of 2-Acetyl-1-pyrroline and of 2-Propionyl-1-pyrroline, Key Roast-Smelling Odorants in Food . Inclusion Complexes with beta-Cyclodextrin and Their NMR and MS Characterization; Favino TF et al.; The synthesis of the strong natural roast odorants 1 and 2 is achieved from the C-6 isomeric alcohols 16 and 21 via the acetylenic C-6 and C-7 amines 8 and 9 . Key step in the process is the hydrolysis of the N-phenylacetamides 12 and 13 by means of immobilized penicillin acylase, which affords the 1-amino-4,5-diketones 14 and 15, spontaneously ring closing to 1 and 2 . These latter compounds form inclusion complexes with beta-cyclodextrin, as demonstrated by NMR measurements in deuterated water and FAB-MS spectra.

Drug Saf, 2001, 24(11), 793 - 9
Causality assessment of adverse effects: when is re-challenge ethically acceptable?
Po AL, Kendall MJ.
One of the most difficult tasks in the evaluation of a medicine is whether it causes a particular rare and unusual (idiosyncratic) adverse effect . Such causality assessments are sometimes done by drug de-challenge and re-challenge . When the adverse effect is potentially serious, there is clearly an important decision to be made as to whether the re-challenge is justifiable and hence ethical . The recent controversy about the potential cardiotoxicity of fexofenadine, the fatalities associated with penicillin re-challenge and the fatalities associated with abacavir re-challenge highlight some of the potential serious risks of drug re-challenge . The associated important ethical issues are discussed . In particular, there is the need to ensure respect for the patient and to consider the scientific and social value of the re-challenge . A framework for evaluating and assessing the appropriateness of a particular drug re-challenge is proposed in the light of recent as well as long-standing discussions of drug re-challenge, patient informed consent and the ethics of human experimentation, in general . It is suggested that a drug re-challenge should be approached with the same rigour and standards of documentation as are currently required of clinical trials . Given the potential conflicts of interest inherent with any drug study, it is argued that the safeguards, as may be provided by scrutiny by an ethics committee, are necessary for a drug re-challenge . For the investigator contemplating the conduct of a drug re-challenge we would recommend the following: (i) a careful risk-benefit assessment as part of the decision-making process; (ii) careful scientific preparation, including appropriate expert support and emergency back-up facilities, if re-challenge is deemed necessary; (iii) the writing of a detailed protocol for independent approval and for safeguarding all concerned; and (iv) meticulous record keeping.

Dan Medicinhist Arbog . 1998;:13-41.
Not Available
Norn M.
Ejler Holm (1887-1966) was the chief at the eye department, the Municipal Hospital in Copenhagen in the period 1929-57 . He got the longest period in the history of the department, 28 years . Holms qualification to get the appointment are described, especially in his medical thesis concerning the yellow pigment in the central part of the retina (bleaching opsin) . Never the less he got an unjustified attack from the opponent professor Marius Tscherning (1854-1939) including the theory of duplicity (day function and night function of the human eye), and the German ophthalmic science . The struggle to become professor ophthalmologiae at the University of Copenhagen in 1925 is mentioned . The eye diseases and their therapy in the period are exemplified from original patient records from 1930 (tuberculosis, venerea, dry eye, morsum hirudin etc.), 1940 (chemotherapeutica, trachoma, glaucoma etc.) and 1949 (penicillin, injections of milk i.m., cauterisation, trachoma etc.), supplemented by Holms records from own practic in 1934, surgery protocols and statistical material from the period . The number of cataract extractions (extracapsular) increased considerable with more liberal indication and regime . Also the number of squint operations are increasing, where sutures are more often used . Glaucoma-surgery increased only slightly with more filtering operations (Elliots trepanation, Holth-iridencleise) instead of simple iridectomy . Eye pathological examinations become more qualified . Psychiatric, simulating and troublesome patients are described . There are very great difference between diagnosis and treatment at that time, compared with today.

Hist Sci Med, 1996, 30(4), 501 - 10
Not Available
Tilles G, Wallach D.
Prior to the first use of penicillin against syphilis in 1943, mercury had a prominent position in the medical practice despite a tremendous toxicity and a questionnable efficiency . In fact, during 450 years mercury remained the guarantee of efficacy . The modalities of use increased, the durations of treatment lengthened without any evidence of a worsening morbidity . This history of an exceptionnal duration seems to be a good example of the weight of tradition or habit in the medical practice, of the importance of the constraints supported by the patients, of the necessity and the difficulties to evaluate the treatments without error.

Nord Medicinhist Arsb . 1996;:189-95.
Not Available
Diamant H, Hultcrantz M.
The history of otitis media has much in common with the history of other infectious diseases . Over the years France, England and Germany respectively dominated the field and treatment of otitis media . During the French period (eighteenth and nineteenth century), Louis Petit for the first time performed an operation with opening of the mastoid cells . In the last decades of the nineteenth century, during the English period, many famous ear doctors spread their names over the world, namely J . Toynbee, J . Hinton and W . Wild of which the latter 1853, wrote the first text book in the field called "Practical observations on aural surgery and the nature and treatment of diseases of the ear." During the German period the surgical treatment (mastoidectomy) of otitis media and its sequele was fullfilled by A . von Troltsch, H . Schwartze and A . Politzer who together started the first journal "Archiv fur Ohrenheilkunde" . Politzer also 1873, started the first ear clinic in Europe, in Vienna . It was almost a rule, that all ear surgeons in Europe during that time, had to visit the ear clinic in "Allgemaines Krankenhaus" in Vienna to gain a proper education . 1940 B . Chain, V . Fleming and H . Florey invented the penicillin and were rewarded with the Nobel prize, and from then on the treatment of otitis media changed dramatically.

Chiropr Hist, 1996 Jun, 16(1), 72 - 87
Chiropractic's tension with the germ theory of disease; Wiese G; After briefly reviewing the development of the germ theory of disease, the author delineates the opposition that the germ theory met from many practitioners, especially chiropractors . This paper explores the evolution of chiropractic's position regarding the germ theory of disease and its dominance in medicine's approach to prophylactic therapy by surveying the chiropractic literature . If the number of monograph and journal publications is indicative of the degree of chiropractic sentiment against the germ theory, the opposition to the theory was heaviest in the 1940's, trailing off to only the occasional monograph or journal article in the 1970's and beyond . Although the development of penicillin and the Salk vaccine may be tied to the demise of most published chiropractic opposition to the germ theory of disease, the basic differences between medicine's approach and chiropractic's approach to disease still remain . Although the differences may be ones of degree, the approaches taken as to whether disease is caused and cured from within the body or from outside the body remains a very real philosophical distinction between the two methods of health care.

Vesalius, 1996 Dec, 2(2), 126 - 31
Not Available
Goens J.
The literary perception of venereal diseases in the XIXth century was radically modified by the big prophylactic campaign that began at its end . After writers presented a romantic vision of syphilis associated initially with pride and exaltation, came a generation distressed by the obsession and the phobia that the antivenereal reaction then generated . The moving elements of this campaign, were the extreme attention to overvalued statistics and excessive consideration of indirect transmission; but also such mythical concepts as parasyphilis, syphilitic diathesis, "le genie syphilitique" and especially "heredosyphilis" . This antivenereal campaign, appearing as a sanitary prophylaxis invented by the syphiligraphes, rapidly changed to a moral prophylaxis, using intensively dissuasive methods and generating among others a true propaganda literature . After World War I, the fear of a degeneration of the race, weakened by depopulation, caused an intensification of the propaganda . Its protectionist, xenophobic and intolerant nature then grew considerably in the militant literature to merge into the themes that have characterized the political speech of the Hitlerian period . The Allies and penicillin fortunately put an end to this delirious rhetoric.

J Microbiol Immunol Infect, 2001 Sep, 34(3), 220 - 3
Childhood serum sickness: a case report; Chao YK et al.; Childhood serum sickness is a rare allergic disease that follows the administration of a foreign antigenic material, most commonly caused by injecting a protein or haptenic drug . The disease is a type III hypersensitivity reaction mediated by deposits of circulating immune complexes in small vessels, which leads to complement activation and subsequent inflammation . The clinical features are fever, cutaneous eruptions, lymphadenopathy, arthralgias, albuminuria, and nephritis . Serum sickness is an acute self-limited disease . We report a 3-year-old child who presented with fever and a rash; an invasive bacterial infection was strongly suspected . He was therefore given penicillin and gentamicin and responded well . At day 4 after admission, he developed a serum sickness reaction and showed symptoms of arthralgias, generalized edema, purpura, and gross hematuria . The white blood cell count was 12 190/mm3 with 7% eosinophils . Urinalysis revealed red blood cell above 100 per high power field, white blood cell 10 to 15 per high power field, and proteinuria . The antibiotics were discontinued and hydrocortisone (20 mg/kg/d), diphenhydramine HCl (4 mg/kg/d), aspirin (66 mg/kg/d) was administered, plus 1 dose of epinephrine (0.01 mL/kg) administered intramuscularly . On day 7, the 3rd day after withholding antibiotics, his condition dramatically improved . The clinical symptoms resolved progressively and his urinalysis returned to normal.

Fresenius J Anal Chem, 2001 Sep, 371(1), 64 - 7
Determination of benzylpenicillin, oxacillin, cloxacillin, and dicloxacillin in cows' milk by ion-pair high-performance liquid chromatography after precolumn derivatization; Marchetti M et al.; A high-performance liquid-chromatographic method has been developed for the determination of five penicillin compounds (benzylpenicillin, phenoxymethylpenicillin, oxacillin, cloxacillin, and dicloxacillin) at trace levels in commercially available milk samples . This method comprises extraction of the lipids with ethyl acetate, clean-up and concentration on a C-18 solid-phase extraction column, and derivatization with 1,2,4-triazole and mercury(II) chloride solution, pH 8, at 65 degrees C for 10 min . The derivatized compounds are eluted from a C-2 column with a mobile phase containing acetonitrile and phosphate buffer loaded with sodium thiosulfate and tetrabutylammonium hydrogen sulfate as ion-pairing reagent . The limit of determination was found to be 4 microg L(-1) milk for benzylpenicillin and 10 microg L(-1) for the others . This meets EU criteria according to decision No . 93/256/EEC.

Presse Med, 2001 Sep 22, 30(26), 1305 - 12
{Helicobacter pylori eradication . Therapeutic evolution, value of complementary studies}; Bigard MA; INDICATIONS: Eradication of Helicobacter pylori is needed for patients with a gastroduodenal ulcer associated with H . pylori gastritis . Eradication modifies the natural history of the disease and greatly reduces the risk of recurrence . Eradication is also indicated for patients with MALT lymphoma with a low degree of malignancy . Systematic eradication of H . pylori would not be necessary for patients with dyspepsia associated with H . pylori gastritis since a beneficial effect is achieved in only 5% of the treated patients . Systematic eradication in order to reduce the incidence of gastric adenocarcinoma is not recommended . DIAGNOSIS: Direct tests (urease, pathology) provide the diagnosis of H . pylori gastritis . Indirect tests (13C-labeled urea respiratory test) can be most useful to determine the efficacy of eradication treatments . THERAPY: A tri-therapy regimen given for 7 days combining a double-dosed proton pump inhibitor, amoxicillin (2 g/d), and clarithromycin (0.5 g b.i.d) is used to eradicate H . pylori . With this regimen, the mean rate of eradication achieved in France is 67% . The principal causes of failure are poor compliance and bacterial resistance to clarithromycin . Metronidazole (1 g/d) can be used for patients allergic to penicillin . A second cycle can be prescribed in case of failure, substituting metronidazole for clarithromycin . FOLLOW-UP: Eradication treatment is prescribed for patients with an ulcer after confirmation of infection by one or two direct tests . Treatment efficacy can be assessed by the respiratory test for patients with a duodenal ulcer but is not systematically needed . Biopsy of a gastric ulcer can also provide an assessment of treatment efficacy . For patients with a non-complicated duodenal ulcer, antisecretion treatment is not required in addition to eradication treatment.

J Mol Biol, 2001 Oct 12, 313(1), 139 - 50
Crystal structures of penicillin acylase enzyme-substrate complexes: structural insights into the catalytic mechanism; McVey CE et al.; The crystal structure of penicillin G acylase from Escherichia coli has been determined to a resolution of 1.3 A from a crystal form grown in the presence of ethylene glycol . To study aspects of the substrate specificity and catalytic mechanism of this key biotechnological enzyme, mutants were made to generate inactive protein useful for producing enzyme-substrate complexes . Owing to the intimate association of enzyme activity and precursor processing in this protein family (the Ntn hydrolases), most attempts to alter active-site residues lead to processing defects . Mutation of the invariant residue Arg B263 results in the accumulation of a protein precursor form . However, the mutation of Asn B241, a residue implicated in stabilisation of the tetrahedral intermediate during catalysis, inactivates the enzyme but does not prevent autocatalytic processing or the ability to bind substrates . The crystal structure of the Asn B241 Ala oxyanion hole mutant enzyme has been determined in its native form and in complex with penicillin G and penicillin G sulphoxide . We show that Asn B241 has an important role in maintaining the active site geometry and in productive substrate binding, hence the structure of the mutant protein is a poor model for the Michaelis complex . For this reason, we subsequently solved the structure of the wild-type protein in complex with the slowly processed substrate penicillin G sulphoxide . Analysis of this structure suggests that the reaction mechanism proceeds via direct nucleophilic attack of Ser B1 on the scissile amide and not as previously proposed via a tightly H-bonded water molecule acting as a "virtual" base .

Biotechnol Appl Biochem, 2001 Oct, 34(Pt 2), 127 - 33
Stability enhancement of Escherichia coli penicillin G acylase by glycosylation with yeast mannan; Masarova J et al.; Penicillin G acylase (PGA) from Escherichia coli was cross-linked with mannan dialdehydes . Conjugates were prepared with molecular masses varying from 140 to 580 kDa and containing from 18 to 50% (w/w) saccharides, the values depending on the reaction conditions (mannan/enzyme ratio), and by using mannans with different degrees of oxidation and weight-average molecular mass (M macro(w)) . The pH- and thermo-stability of all preparations of glycosylated enzyme were improved remarkably, whereby the influence of the character of the linked mannan dialdehyde, its content, as well as the molecular mass of prepared glycoconjugates, on the stability of PGA, was evaluated . PGA glycosylated with the most oxidized mannan up to an M(w) of 490 kDa, containing 41% (w/w) saccharides, and retaining 90% of its original catalytic activity, showed the highest stability . The half-life of this PGA preparation increased significantly: 13-fold at pH 3, 7-fold at pH 10, and 3.5-fold at pH 8 (all at 37 degrees C), compared with the native enzyme . At higher temperatures (50 degrees C) even more significant stabilization was evident, a 16-fold increase in half-life, from 18 min to 289 min, at pH 8, being measured.

J Pediatr Surg, 2001 Oct, 36(10), 1577 - 8
Disseminated actinomycosis presenting as a renal tumor with metastases; Hilfiker ML; Disseminated actinomycosis is uncommon in the pediatric population and rarely presents as a renal mass mimicking a renal tumor with metastases . Diagnosis may be difficult . In this case, percutaneous biopsy results only showed necrosis and fibrosis and, hence, were not helpful in diagnosis . Exploratory laparotomy and open biopsy results showed that this renal tumor was an actinomycotic abscess with similar abscesses in the liver and lung masquerading as metastases . The treatment for disseminated actinomycosis is with parenteral and oral penicillin .

Med Trop (Mars), 2001, 61(2), 169 - 72
{A classical form of actinomycoses involving the mouth, face bones, orbit and base of the cranium in an African patient}; Badiaga S et al.; Osteitis due to actinomycosis is now an uncommon clinical entity in industrialized countries . This report describes a classic case of imported actinomycosis involving the buccal cavity, facial bones, orbit and skull base . For two years after the onset, various diagnoses followed by different medical as well as surgical treatments were unsuccessfully attempted first in Senegal then in Italy . Proper diagnosis was finally established in Marseille, France, on the basis of histological findings after extensive surgical biopsy . The patient was treated with high-dose intravenous penicillin G for four weeks followed by daily oral administration of amoxicillin for one year . Surgical reconstruction could not be carried out before the patient's return to Senegal . The pitfalls of diagnosis and treatment of actinomycosis are discussed.

Can J Gastroenterol, 2001 Sep, 15(9), 615 - 7
An unusual case of hepatic abscess; Tambay R et al.; A case of recurring primary hepatic actinomycosis is reported . A 50-year-old man presented with fever, weight loss and multiple hepatic masses . A diagnosis was obtained by cytological examination of a biopsy sample taken from the largest hepatic mass, which revealed the presence of Actinomyces species . The patient was treated with penicillin for 12 months and did well . Seven years later, he presented with similar symptoms but with a single large liver mass and a pulmonary infiltrate in the right lower lobe . Liver biopsy showed an inflammatory pseudotumour, and lung biopsy showed the presence of Actinomyces species . Again, the patient was treated with penicillin . Five months later, the patient was doing well, and a follow-up computed tomography scan showed partial regression of the hepatic pseudotumour . This case indicates that hepatic actinomycosis can recur several years after an appropriate treatment and stresses the need for careful follow-up in such patients.

Ann Allergy Asthma Immunol, 2001 Sep, 87(3), 238 - 42
Delayed hypersensitivity to cefazolin: report on a case involving lymphocyte transformation studies with different cephalosporins; Romano A et al.; BACKGROUND: A cell-mediated immunopathogenic mechanism has been demonstrated in only a few cases of cutaneous reactions to systemically administered cephalosporins . OBJECTIVE: The aim was to investigate the pathogenic mechanism of a maculopapular rash experienced by a subject during cefazolin therapy . METHODS AND RESULTS: Prick, intradermal, and patch tests were carried out using penicillin determinants, ampicillin, amoxicillin, cefazolin, cephalothin, cefuroxime, ceftazidime, and ceftriaxone . Those tests for penicillin G and its determinants, as well as for ampicillin and amoxicillin, were negative . The patient displayed patch-test and delayed intradermal-test positivity to all the cephalosporins tested . No specific immunoglobulin E antibodies were found for penicillins or cefazolin . The lymphocyte-transformation-test results were negative for all the penicillins tested and showed a positive concentration-effect curve for cefazolin, ceftazidime, and ceftriaxone at concentrations up to 50 microg/mL . At 100 microg/mL the responses decreased with all the cephalosporins tested . Challenges with penicillin G and amoxicillin were well tolerated, but the challenge with cefazolin was positive . CONCLUSIONS: The data of this case demonstrate delayed hypersensitivity to cefazolin . Patch tests and delayed-reading intradermal tests can be a simple and effective means of diagnosing this type of reaction . Both in vivo and in vitro studies indicate that the responses were directed toward a determinant shared by all cephalosporins, but not by penicillins . The concentration of the cephalosporins used for the in vitro lymphocyte stimulation was critical, because at the concentrations normally used to test other beta-lactams the response decreased . This phenomenon may be attributable to an immunosuppressive, rather than toxic, effect.

Am J Forensic Med Pathol, 2001 Sep, 22(3), 292 - 5
An unusual case of anaphylaxis . Mold in pancake mix; Bennett AT et al.; Anaphylactic reactions involve contact with an antigen that evokes an immune reaction that is harmful . This type of reaction is a rapidly developing immunologic reaction termed a type I hypersensitivity reaction . The antigen complexes with an IgE antibody that is bound to mast cells and basophils in a previously sensitized individual . Upon re-exposure, vasoactive and spasmogenic substances are released that act on vessels and smooth muscle . The reaction can be local or systemic and may be fatal . The authors report the death of a 19-year-old white male who had a history of "multiple allergies," including pets, molds, and penicillin . One morning, he and his friends made pancakes with a packaged mix that had been opened and in the cabinet for approximately 2 years . The friends stopped eating the pancakes because they said that they tasted like "rubbing alcohol." The decedent continued to eat the pancakes and suddenly became short of breath . He was taken to a nearby clinic, where he became unresponsive and died . At autopsy, laryngeal edema and hyperinflated lungs with mucous plugging were identified . Microscopically, edema and numerous degranulating mast cells were identified in the larynx . The smaller airways contained mucus, and findings of chronic asthma were noted . Serum tryptase was elevated at 14.0 ng/ml . The pancake mix was analyzed and found to contain a total mold count of 700/g of mix as follows: Penicillium, Fusarium, Mucor, and Aspergillus . Witness statements indicate that the decedent ate two pancakes; thus he consumed an approximate mold count of 21,000 . The decedent had a history of allergies to molds and penicillin, and thus was allergic to the molds in the pancake mix . The authors present this unusual case of anaphylaxis and a review of the literature.

J Microbiol Immunol Infect, 1999 Jun, 32(2), 129 - 32
Leptospirosis: report of one case; Wang SC et al.; An 8-year-old male aborigine was referred to our hospital with a presumptive diagnosis of Kawasaki disease . The major symptom presented was a persistent fever for six days . Several other symptoms were drowsiness, headache, nausea, vomiting, abdominal pain, diarrhea, nuchal rigidity, lymphadenopathy, subconjunctival hemorrhage, and muscle aching of the calf . During hospitalization, cerebrospinal fluid studies showed pleocytosis . Abdominal sonograms revealed hepatosplenomegaly, moderate ascites and gallbladder wall thickening . These data were suggestive of leptospirosis . The microscopic agglutination test of leptospiral antibodies further confirmed the diagnosis . After treatment with intravenous aqueous penicillin and gentamicin, the clinical course improved significantly.

Z Gastroenterol, 2001 Aug, 39(8), 587 - 92
{Fulminant course of leptospirosis complicated by multiple organ failure}; Kirchner GI et al.; We describe a case of a 39-year-old male, who initially presented with severe muscle pain, fever, shortness of breath and tachycardia . He was admitted to hospital with suspected myocarditis . The next days he developed a generalized icterus and acute renal failure . Suspecting leptospirosis an intravenous therapy with penicillin was started . Due to pulmonary and circulatory insufficiency intensive care was necessary . In course the patient developed all known manifestations of leptospirosis including, cardiac arrhythmia and asystolia due to AV-block III degrees, recurrent atelectases of the lungs, hyperbilirubinemia, thrombocytopenia, hepatitis, pancreatitis, very severe rhabdomyolysis and polyradiculitis with areflexia and tetraplegia . Additionally, the patient had a transient hyperthyreosis, which has not been described in the literature so far . After 33 days the patient left the intensive care unit and was discharged out of hospital a fortnight later . 4 weeks later he was able to return to work . The only residuum of this illness is a partial paresis of his right quadriceps muscle.

East Mediterr Health J, 2000 Mar-May, 6(2-3), 437 - 46
Profile of secondary prophylaxis among children with rheumatic heart disease in Alexandria, Egypt; Bassili A et al.; A cross-sectional study was conducted in specialist children's hospitals in Alexandria, which aimed to evaluate the current regimen of secondary prophylaxis for children suffering from rheumatic heart disease . Two-thirds of the patients had complied with their prophylactic regimen . Prophylactic failure occurred in one-third of the patients, raising doubts about the efficacy of the brands of penicillin prescribed . Recurrence of rheumatic fever was recorded in 37.3% of the patients, with semiruban or rural residence and non-compliance with secondary prophylaxis the significant risk factors . These unsatisfactory findings suggest the need for a more effective strategy of primary and secondary prophylaxis for controlling rheumatic fever in our community.

Rev Alerg Mex, 2001 May-Jun, 48(3), 80 - 7
{Skin tests with high and minor determinants in patients with doubtful allergy to penicillin}; Lopez Tiro JJ et al.; BACKGROUND: Currently, the skin tests are the most accepted methods for the diagnosis of allergy to penicillin . OBJECTIVE: To evaluate the efficacy and diagnosis security of the skin tests with high and minor determinants of penicillin, crystalline and penicillin, in patients with hypersensitivity reaction to penicillin . METHODS: Patients with doubtful antecedents of reaction to penicillin (problem group) and healthy patients (control group) were included . Both groups were submitted at the following tests: 1) Skin tests with high and minor determinants of penicillin, and crystalline penicillin, by prick and intradermoreaction methods . 2) In case of negativity, tests of direct challenge with penicillin were practiced . The formation of wheal with or without erythema 3 mm related to the negative control or systemic reaction, was considered positive test . RESULTS: 47 patients were included (24 for problem group, and 23 for control group), 50% of the group problem showed positive reactions with the method of prick, none patient of the control group (p < 0.001); with the intradermoreaction method, 79% in the problem group and only 13.4% in the control group showed positive reaction (p < 0.001) . Cutaneous tests showed local adverse effects . Clinical history showed a sensitivity or 88%, method of prick, 50%, and intradermoreaction method, 95%.

Allergy, 2001 Sep, 56(9), 862 - 70
Clinical evaluation of Pharmacia CAP System RAST FEIA amoxicilloyl and benzylpenicilloyl in patients with penicillin allergy; Blanca M et al.; BACKGROUND: The diagnosis of IgE-mediated immediate reactions to penicillins can be supported by in vivo or in vitro tests using classical benzylpenicillin determinants . The wide variety of beta-lactams and the description of new specificities requires a re-evaluation of the different tests available . The objective was to evaluate the diagnostic capacity of Pharmacia CAP System RAST FEIA amoxicilloyl c6 (AXO) and benzylpenicilloyl c1 (BPO) in patients with a documented IgE-mediated penicillin allergy . METHODS: We studied 129 patients in five groups . Groups 1, 2, and 3 had developed an immediate reaction after penicillin treatment . Group 1 (n=19) were skin test positive to amoxicillin (AX) and/or BPO and/or minor determinant mixture (MDM); group 2 (n=29) were skin test positive to AX but negative to BPO and MDM; and group 3 (n=26) were skin test negative to all determinants, the diagnosis being confirmed by a previous repetitive history or controlled administration . Two control groups, one with nonimmediate reactions -- group 4 (n=25) -- and one with good tolerance to penicillin -- group 5 (n=30) -- were included . All samples were analyzed in vitro for AXO and BPO, and the results compared to the in vivo diagnosis . RESULTS: AX was the drug most often involved . In group 1, 53% were in vitro positive for AXO and 68% for BPO, but 74% had at least one positive test result . In group 2, only 10% had a positive in vitro test to BPO compared to 41% to AXO . In group 3, 42% had positive BPO and/or AXO in vitro tests . In the control groups 4 and 5, the negative in vitro results for AXO were 96% and 100%, and for BPO 100% and 97%, respectively . A positive correlation between specific IgE levels and the time interval from the reaction to the evaluation was found only for group 3 . CONCLUSIONS: This in vitro assay is beneficial for evaluating subjects allergic to beta-lactams . It is necessary to test for specific IgE to AXO in addition to BPO in patients with immediate allergic reactions after AX . The combination of in vivo and in vitro tests for estimating IgE antibodies to penicillins is important because of the existence of patients with a positive history but negative skin test.

Allergy, 2001 Sep, 56(9), 850 - 6
Diagnostic evaluation of a large group of patients with immediate allergy to penicillins: the role of skin testing; Torres MJ et al.; BACKGROUND: Penicillin is no longer the most commonly prescribed beta-lactam, and the pattern of reactions has changed . We studied the diagnostic value of skin testing in penicillin-allergic subjects from a population where benzylpenicillin is not now the most frequently used beta-lactam . METHODS: Patients with a history of immediate allergic reactions to penicillins were studied with: skin tests with major and minor determinants of benzylpenicillin (BPO/MDM), amoxicillin, and ampicillin; in vitro determination of specific IgE; and controlled administration for those with a positive history but negative skin and in vitro tests . A reaction was considered immediate when symptoms appeared within a maximum of 1 h after drug intake . RESULTS: After testing, 290 patients (71% having anaphylaxis and 29% having urticaria) proved to be allergic . Amoxicillin was involved in 64.8% and benzylpenicillin in 2.8% of the patients . Skin test positivity to at least one determinant appeared in 70% of cases, amoxicillin being the most frequent . The overall sensitivity decreased markedly when only BPO and MDM were considered . In 13.1% of patients, the diagnosis was established by in vitro test and in 16.9% by controlled administration . Of the 290 patients, 42.1% were positive to determinants generated from benzylpenicillin and 57.9% were selective responders . CONCLUSIONS: Sensitivity of skin tests to BPO was lower than reported, being partly replaced by minor determinants, mostly amoxicillin . The incorporation of additional reagents and the development of new tests are required, and these will probably change as the patterns of consumption vary.

Zh Mikrobiol Epidemiol Immunobiol, 2001 May-Jun, (3), 11 - 3
{Effect of metal ions on Escherichia coli NAT 99-50R penicillin acylase production}; Aleksakhina NN et al.; The processes of growing E . coli NAT 99-50R in a synthetic nutrient medium containing metal salts (iron nitrate, lutecium nitrate or cerium nitrate) were carried out . As shown in experiments, the addition of metal salts at different concentrations into the medium produced different impact on the penicillinase activity of the culture . This activity increased 7- to 10-fold when the bacteria were grown in a synthetic medium with iron nitrate added at a concentration of 0.0001% or with lutecium nitrate added at a concentration of 0.01%.

Methods Cell Sci, 2000, 22(4), 277 - 84
Effect of pH and Zn(2+) on subcultured muscle cells from Macrobrachium nipponense; Wang WN et al.; A cell culture system was devised for muscle cell of Macrobrachium nipponense in the study . The juvenile and adult shrimps were held in laboratory aquaria with penicillin 1000 IU/ml and streptomycin 1000 microg/ml for 12-24 hours . Cell cultures were established in medium 199 supplemented with 20% fetal bovine serum, 1 g/L glucose, 5.2 g/L NaCl, 1.43 g/L CaCl(2), 0.05 g/L MgCl(2), 100 IU/mL penicillin and 100 microg/ml streptomycin . Fibroblast-like cells were passaged up to three times and survived for 54 days . The results showed the optimum for subculture in vitro was in medium 199 with pH 7.6 . Moreover, basal medium supplemented with Zn(2+) 60 microg/L could enhance the growth of the muscle cells . It was found that better results for cell culture would be obtained more easily with juvenile shrimps caught in spring than adults in summer or autumn; and shrimps caught within 12 hours after ecdysis could grow much better than the intermoult shrimps.

Bioorg Med Chem Lett, 2001 Sep 17, 11(18), 2511 - 4
Contrasting fates for 6-alpha-methylpenicillin N upon oxidation by deacetoxycephalosporin C synthase (DAOCS) and deacetoxy/deacetylcephalosporin C synthase (DAOC/DACS); Hamilton CS et al.; 6-alpha-methylpenicillin N was synthesised via known routes from 6-aminopenicillanic acid, and tested as a substrate for recombinant DAOCS and DAOC/DACS . Incubation with DAOCS resulted in conversion of 2-oxoglutarate without oxidation of the penicillin substrate ('uncoupled turnover') . Incubation with DAOC/DACS resulted in oxidation to the cephem aldehyde . This is the first example of substrate-induced 'uncoupled turnover', which has been proposed to be an editing mechanism for these enzymes.

Natl Med J India, 2001 Jul-Aug, 14(4), 202 - 4
Audit of management of pregnant women with positive VDRL tests; Mathai E et al.; BACKGROUND: Syphilis is a preventable cause of foetal loss and congenital disease . Although the VDRL test is an integral part of routine antenatal care in India, little is known about the disease burden in pregnancy in India . Therefore, we carried out a study to determine the prevalence of VDRL positivity and syphilis among pregnant women in Vellore and to audit the management and outcome of VDRL-positive pregnancies . METHODS: A retrospective review of case records . RESULTS: Only 0.98% of pregnant women were positive by the VDRL test . However, foetal loss occurred in 16 (32%) of the 50 seropositive women; 15 of these did not receive antenatal care . Seventeen of the 34 seropositive multiparous women had had previous foetal losses . Only 16 women had received penicillin . CONCLUSION: Although the seroprevalence of syphilis in pregnancy is low, it is an unrecognized cause of foetal loss in Vellore . An audit of the testing and management of VDRL positivity in pregnancy provides valuable information on the quality of antenatal care in an area.

J Bacteriol, 2001 Oct, 183(19), 5465 - 71
Reduced function of a phenylacetate-oxidizing cytochrome p450 caused strong genetic improvement in early phylogeny of penicillin-producing strains; Rodriguez-Saiz M et al.; The single-copy pahA gene from Penicillium chrysogenum encodes a phenylacetate 2-hydroxylase that catalyzes the first step of phenylacetate catabolism, an oxidative route that decreases the precursor availability for penicillin G biosynthesis . PahA protein is homologous to cytochrome P450 monooxygenases involved in the detoxification of xenobiotic compounds, with 84% identity to the Aspergillus nidulans homologue PhacA . Expression level of pahA displays an inverse correlation with the penicillin productivity of the strain and is subject to induction by phenylacetic acid . Gene expression studies have revealed a reduced oxidative activity of the protein encoded by pahA genes from penicillin-overproducing strains of P . chrysogenum compared to the activity conferred by phacA of A . nidulans . Sequencing and expression of wild-type pahA from P . chrysogenum NRRL 1951 revealed that an L181F mutation was responsible for the reduced function in present industrial strains . The mutation has been tracked down to Wisconsin 49-133, a mutant obtained at the Department of Botany of the University of Wisconsin in 1949, at the beginning of the development of the Wisconsin family of strains.

Biotechnol Bioeng, 2001 Oct 5, 75(1), 46 - 52
A chemostat culture as a tool for the improvement of a recombinant E . coli strain over-producing penicillin G acylase; Maresova H et al.; The recombinant strain RE3(pKA18) of Escherichia coli constitutively overproduces penicillin G acylase (PGA) from plasmid-borne gene pga . The host strain RE3 bears the same pga gene on its chromosome, the expression of which is controlled by the natural mechanism of induction with phenylacetic acid (PA) . To evaluate the maximum biosynthetic capacity for PGA, induction of the chromosomal pga by PA was studied in a culture of the recombinant strain . PGA production by batch cultures of RE3(pKA18) and RE3 showed a different response to the addition of PA to the medium: while an addition of PA induces PGA in a culture of strain RE3 as expected, in recombinant cells it lowers the specific activity of PGA and a large amount of PGA is released into the culture medium . To improve the PGA production, the strain RE3(pKA18) was cultured in a carbon-limited chemostat and subjected to selection pressure in a medium supplemented with phenylacetic acid amide (PAA) . Phenylacetic acid amide served as a source of nitrogen, an inducer of PGA and a factor exerting positive selection pressure on the maintenance of the recombinant plasmid . After 130 generations of growth in the presence of the inducer, no recombinant strain with constitutive expression of the chromosomal gene pga was detected in the prevailing P(+) subpopulation in the chemostat . Shake-flask experiments with the parent recombinant strain RE3(pKA18), host strain RE3, chemostat evolvant ERE3(epKA18), the cured host ERE3 alone, and its derivative after retransformation with ancestral plasmid ERE3(pKA18) showed that inactivation of the plasmid-borne pga by a frame-shift mutation (plasmid epKA18) occurred in the plasmid-bearing subpopulation accumulated in the chemostat . Marked adaptive changes evolved in the host ERE3 during a 130 generation culture: (1) the specific growth rate of the host increased by 30% in a medium without PA, (2) the copy number of plasmids pKA18 and epKA18 in the host cultured in PA-free medium dropped by about 40%, and (3) the leakage of PGA from the cell in the presence of PA found in strain RE3(pKA18) was not observed in strain ERE3(pKA18) . This new recombinant strain with modified traits was constructed by means of retransformation of the evolved host ERE3 with ancestral plasmid pKA18 .

Clin Infect Dis, 2001 Oct 1, 33(7), 983 - 9 Epub 2001 Sep 05.
Randomized, placebo-controlled clinical trial of oral azithromycin prophylaxis against respiratory infections in a high-risk, young adult population; Gray GC et al.; Military Special Forces trainees undergo intense psychological and physical stressors that often lead to respiratory infection . During 1998-2000, 477 Navy Special Forces trainees were enrolled in a double-blind trial of oral azithromycin (1 g given weekly) plus a placebo injection, compared with benzathine penicillin G (1.2 million U) plus azithromycin placebo tablets . Among the 464 subjects with complete data, 44 developed acute respiratory infection (20 with pneumonia) during the 2 weeks of most intense training; of these subjects, 12 (27.3%) had evidence of Chlamydia pneumoniae infection and 7 (15.9%) had evidence of Mycoplasma pneumoniae infection . Trainees who received azithromycin were less likely than were trainees who received benzathine penicillin G to develop acute respiratory infection (risk ratio, 0.50; 95% confidence interval {CI}, 0.28-0.92) and less likely at the end of training to report episodes of breathing difficulty (odds ratio {OR}, 0.59; 95% CI, 0.34-1.01) or sore throat (OR, 0.66; 95% CI, 0.41-1.05) . Compared with benzathine penicillin G prophylaxis, weekly oral azithromycin was superior in preventing respiratory infection in this population at transient high risk.

Biophys Chem, 2001 Aug 30, 92(1-2), 141 - 53
Adsorption of an amphiphilic penicillin onto human serum albumin: characterisation of the complex; Ruso JM et al.; The complex formed by the interaction of the amphiphilic penicillin drug nafcillin and human serum albumin (HSA) in water at 25 degrees C has been characterised using a range of physicochemical techniques . Measurements of the solution conductivity and the electrophoretic mobility of the complexes have shown an ionic adsorption of the drug on the protein surface leading to a surface saturation at a nafcillin concentration of 0.012 mmol kg(-1) and subsequent formation of drug micelles in solutions of higher nafcillin concentration . Measurements of the size of the complex and the thickness of the adsorbed layer by static and dynamic light scattering have shown a gradual change in hydrodynamic radius of the complex with increasing drug concentration typical of a saturation rather than a denaturation process, the magnitude of the change being insufficient to account for any appreciable extension or unfolding of the HSA molecule . The interaction potential between the HSA/nafcillin complexes, and the stability of the complexes were determined from the dependence of diffusion coefficients on protein concentration by application of the DLVO colloidal stability theory . The results indicate decreasing stability of the colloidal dispersion of the drug/protein complexes with an increase in the concentration of added drug.

J Gen Physiol, 1966 Nov, 50(2), 369 - 77
Increased mutation rate of E . coli K12 lambda cultures maintained in continuous logarithmic growth; Northrop JH; Continuous logarithmic growth of E . coli K12 lambda in an automatic culture cell resulted in marked increases in the proportion of several mutants . The P1 phage-resistant cells increased 10 to 3000 times, the T2 phage-resistant cells 1 to 1000 times, the neomycin-resistant cells 1 to 10 times, and the virus-producing cells 30 to 70 times . No change occurred in the penicillin-resistant cells . Calculation of the growth curves and direct determination of the mutation rates by the null fraction method showed that the increases in the proportion of mutants were due to increases in the mutation rates.

Scand J Infect Dis, 2001, 33(8), 625 - 7
Clinical "pneumococcal pneumonia" due to Moraxella osloensis: case report and a review; Vuori-Holopainen E et al.; A previously healthy 6-y-old girl presented with a disease very similar to pneumococcal pneumonia . However, Moraxella osloensis was isolated by lung tap . The patient responded well to a course of parenteral penicillin . This is probably the first documented case of community-acquired pneumonia associated with this agent . Clinical isolates of M . osloensis are rare and its pathogenesis has not been delineated; however, a literature review suggests that the organism is more common than is generally recognized.

Postgrad Med J, 2001 Sep, 77(911), 589 - 90
Primary neuroleptospirosis; Panicker JN et al.; Leptospirosis is an important zoonosis of worldwide distribution . It is uncommon for leptospirosis to present as a primary neurological disease . In this study of patients who presented with an acute neurological disease, and who were subsequently found to have leptospirosis, aseptic meningitis was the commonest manifestation . The other presentations were myeloradiculopathy, myelopathy, Guillain-Barre syndrome-like presentation, meningoencephalitis, intracerebral bleed, cerebellar dysfunction, iridocyclitis, and tremor/rigidity . Treatment consists of antibiotics, crystalline penicillin being the drug of choice, which reduces the course of illness if given early . The role of steroids is controversial . The prognosis after primary neuroleptospirosis is generally good but altered sensorium and seizures herald a worse prognosis.

Zentralbl Chir, 2001 Aug, 126(8), 632 - 4
{Acute retrocecal appendicitis caused by an Actinomyces israelii mixed infection}; Mumme T et al.; We report the rare case of a retrocecal appendicitis in an adult caused by an Actinomyces israelii mixed infection . Suspecting an acute appendicitis the explorative laparotomy was performed . Appendectomy with extensive drainage of the abscess and subsequent high-dose penicillin therapy over several months were the definitive treatment, resulting in complete healing . Special features of clinical symptomatology and problems concerning diagnosis and differential diagnosis are discussed.

Ann R Coll Surg Engl, 2001 Jul, 83(4), 279 - 80
A rare and serious consequence of a rat bite; Downing ND et al.; Contact with rat saliva or faeces can lead to infection with Streptobacillus moniliformis and the condition known as 'rat bite fever' . We report a case of septic arthritis of the hip due to this organism following a bite on the finger of a 14-year-old boy from a rat for sale in a pet shop . The case was successfully treated by arthrotomy, drainage and joint lavage followed by administration of penicillin . Septic arthritis of the hip due to S . moniliformis has not been previously described and this case highlights a possible danger of keeping rats as pets.

Eur J Endocrinol, 2001 Sep, 145(3), 311 - 6
Hypoglycaemia due to insulin autoimmune syndrome: report of two cases with characterisation of HLA alleles and insulin autoantibodies; Cavaco B et al.; OBJECTIVE: Insulin autoimmune syndrome (IAS) has been reported mainly in Japan and so far only 27 IAS cases have been described from outside Asia . We describe two unrelated Portuguese patients with IAS and characterise their insulin autoantibodies and HLA alleles . PATIENTS: Patient 1, a 24-year-old white female suffered an episode of unconsciousness in the late postprandial state and blood glucose was found to be 33 mg/dl with serum insulin levels of >3980 microIU/ml (normal range 0-30 microIU/ml) . She was receiving monthly injections of penicillin G for the prophylaxis of recurrent tonsillitis . Patient 2, was a 19-year-old white female, with episodes of sweating, hand tremor, weakness and hunger occurring in the postprandial state and blood glucose levels during the attacks of 28-56 mg/dl . Very high insulin levels (602-708 microIU/ml) were present . METHODS AND RESULTS: Anti-insulin antibodies, determined by a semi-quantitative method, were strongly positive in both patients (91.7% in patient 1 and 88.6% in patient 2; normal range < or =7%) . Sephadex G-100 chromatography of the sera showed most of insulin immunoreactivity present in the void volume which was retained by an affinity column with anti-human-immunoglobulin G antibodies (87% and 95% from patients 1 and 2 respectively) . Scatchard plot analysis and molecular typing of the DRB1 gene revealed a polyclonal antibody and DRB1*0406 in patient 1, and a monoclonal antibody and DRB1*0403 in patient 2 . CONCLUSIONS: These two Portuguese patients with IAS had different HLA-DR4 subtypes and insulin autoantibodies: DRB1*0406 and a polyclonal antibody in a patient treated with penicillin, and DRB1*0403 and a monoclonal antibody in a patient with "idiopathic" IAS.

Nephrol Dial Transplant, 2001, 16 Suppl 5, 73 - 7
Leptospirosis renal disease; Yang CW et al.; Leptospirosis is a re-emerging infectious disease, affecting both animals and humans worldwide . Multiple organ involvement may be encountered in leptospirosis, and early renal involvement is very common, characterized by tubulo-interstitial nephritis and tubular dysfunction . All 12 patients diagnosed in Chang Gung Memorial Hospital (Taiwan) between 1997 and 1999 had acute renal failure, with five patients requiring dialysis . Leptospira shermani is the main serovar encountered in Taiwan, and penicillin may dramatically rescue patients from multiple organ failure provided it is given early . To understand the mechanism behind tubular injuries by leptospira infection, outer membrane proteins (OMPs) extracted from pathogenic leptospira were given to tubular cells in culture . Our in vitro experiment showed that OMPs of pathogenic leptospira activate nuclear NFkappaB binding and stimulate downstream inducible nitric oxide (iNOS), monocyte chemoattractant protein-1 (MCP-1) and tumor necrosis factor-alpha (TNF-alpha) expression . These results indicate that leptospiral infection may induce tubulo-interstitial nephritis through a toxic component in the outer membrane followed by expression of inflammatory genes.

Pol Merkuriusz Lek, 2001 Jun, 10(60), 469 - 72
{Allergy to penicillin: facts and controversies}; Zdziarski P et al.; Correct diagnosis in patients with side effect during benzylpenicillin (penicillin G) treatment is highly problematic . It is accepted, that hypersensitivity to penicillin is overdiagnosed . Very little qualitative information is available on the diagnostic and differentiation of penicillin allergy . On present stage it is not techniques permitting to exclude anaphylaxis . This paper describe topical knowledge about risks administration of benzylpenicillin to patients suspected of penicillin hypersensitivity . Precious advice in diagnostic procedures and therapeutic management was given.

Pol Merkuriusz Lek, 2001 Jun, 10(60), 453 - 5
{Hoigne syndrome as an acute non-allergic reaction to different drugs: case reports}; Zdziarski P; In 1959 Hoigne described the first cases of pseudo-anaphylactic reactions induced by intramuscular administration of procaine penicillin G . This complication, characterized by acute psychological and neurological manifestations, is still of current interest . We report cases of patient, whose Hoigne syndrome was not due to procaine penicillin G (i.e . lidocaine, edan, azlocillin, gentamycin, klaritromycin and cefuroxime) . It is accepted that Hoigne syndrome can be caused by lidocaine . Further Stell i.m . and Ojo OA published similar case report of Amoxycillin-induced hallucinations . These clinical observations indicate also that using term "acute non-allergic reaction to procaine penicillin G" as synonym of Hoigne syndrome is not precise . Further classification of the reaction among psychic disturbances or adverse drug reactions is very difficult . Much of literature is devoted to the differentiation from anaphylaxis rather than other symptoms of main disease or side effects . Harmful effect of main disease is very likely . Lidocaine was taken intravenously by patient with diabetes and heart attack or locally with chronic hepatitis during topical anesthesia . Benzylpenicillin, azlocycillin, gentamycin, klaritromycin and cefuroxime was used during serious bacterial infections . These observations indicate that pathogenesis of Hoigne syndrome may be associated with main disease and organic brain disease . Then procaine kindling mechanism partly explain Hoigne syndrome . Therefore pathogenesis, definition, differentiation and classification of this complication is still unclear.

Sheng Li Xue Bao, 1999 Oct, 51(5), 508 - 14
{Effect of electroacupuncture and 7-NI on penicillin-induced epilepsy and their relation with intrahippocampal NO changes}; Huang ZN et al.; In order to investigate the effect of 7-nitroindazole (7-NI) on penicillin-induced epilepsy and the relationship between NO and anti-epileptic effect of electro-acupuncture, computerized physiological polygraph and NO-sensitive electrode with potentiostat were respectively used to record the total power spectrum (TPS) of EEG and the concentration of NO in rat hippocampus pretreated with electro-acupuncture or 7-NI for 30 min before penicillin . The results showed that the TPS of EEG and concentration of NO in hippocampus increased greatly after the epilepsy induction . Treatment with electroacupuncture inhibited the TPS of EEG sharply (P < 0.01) . The latency and threshold of epilepsy induction were decreased by 7-NI, but paroxysm abated and the TPS was inhibited (P < 0.05) as compared with the control group . Both pretreatments with 7-NI and electroacupuncture decreased the NO concentration (P < 0.01) . The above results suggest that the propagation of penicillin-induced seizures is facilitated by nNOS, but with some increase in the latency and threshold of induction . Electroacupunture may inhibit seizure through decreasing nNOS transcription in hippocampus.

J Endod, 2001 Feb, 27(2), 117 - 23
Effect of penicillin on postoperative endodontic pain and swelling in symptomatic necrotic teeth; Henry M et al.; The purpose of this prospective, randomized, double-blind, placebo-controlled study was to determine the effect of penicillin on postoperative pain and swelling in symptomatic necrotic teeth . Forty-one emergency patients participated and each had a clinical diagnosis of a symptomatic necrotic tooth with associated periapical radiolucency . After endodontic treatment patients randomly received a 7-day oral dose (twenty-eight 500 mg capsules to be taken every 6 h) of either penicillin or a placebo control in a double-blind manner . Patients also received ibuprofen; acetaminophen with codeine (30 mg); and a 7-day diary to record pain, percussion pain, swelling, and number and type of pain medication taken . The majority of patients with symptomatic necrotic teeth had significant postoperative pain and require analgesic medication to manage this pain . The administration of penicillin postoperatively did not significantly (p > 0.05) reduce pain, percussion pain, swelling, or the number of analgesic medications taken for symptomatic necrotic teeth with periapical radiolucencies.

Eur J Neurosci, 2001 Jul, 14(1), 174 - 8
Discharge threshold is enhanced for several seconds after a single interictal spike in a model of focal epileptogenesis; de Curtis M et al.; Interictal spikes (ISs) are typically observed between seizures in focal epilepsies . Whether ISs are causally involved or represent protective elements in the transition toward an ictal discharge is an open question . Previous studies suggested that inhibition or disfacilitation occurs during the period elapsing between two ISs induced by local application of either bicuculline or penicillin in the piriform cortex of the in vitro isolated guinea pig brain preparation . We further investigated this issue by studying responses to afferent stimulation during the interspike period (6.3 +/- 2.5 s; mean +/- SD) . Properly set stimulation intensity of the lateral olfactory tract resets ISs exclusively (and not before) 4-10 s (5.6 +/- 2.0 s; mean +/- SD) after a preceding spontaneous spike . This finding demonstrates the existence of a period of enhanced threshold to stimulus-evoked activation that coincides with the interspike interval in the absence of stimulation . Current source density analysis of depth laminar profiles demonstrated that both stimulus-evoked and spontaneous ISs were generated by the activation of an identical cortical circuit . Our study suggests that interictal spiking could play a protective role or at least provide an effective restraint against the onset of a focal ictal discharge.

Jpn J Pharmacol, 2001 Jul, 86(3), 297 - 301
Effects of L-arginine on penicillin-induced epileptiform activity in rats; Marangoz C et al.; It has been suggested that nitric oxide (NO) is involved in the pathophysiology of epilepsy . Data are, however controversial because it is not clear whether NO has pro- or anticonvulsant effects . The aim of this study was to investigate the effects of NO on penicillin G-induced epileptiform activity . The left cerebral cortex was exposed by craniotomy in urethane-anesthetized Wistar rats . The epileptic activity was produced by intraperitoneal injection of penicillin G (3 million U/kg, i.p.) . The ECoG (electrocorticogram) activity was displayed on a four-channel recorder . At 39.7 +/- 5.4 min after penicillin administration, large amplitude sharp waves appeared in the ECoG . Mean spike frequency and mean spike amplitude were calculated as 29.5 +/- 3.2/min and 865 +/- 91 microV, respectively, at the 55th min . 7-Nitroindazole (60 mg/kg, i.p.) injection 30 min before penicillin G administration significantly reduced the latency of epileptiform activity . Intracerebroventricular administration of L-arginine (300 microg/2 microl, i.c.v.) and sodium nitroprusside (100 microg/2 microl, i.c.v.) suppressed epileptiform activity . Saline (2 microl) and D-arginine (300 microg/2 microl, i.c.v.) administration into the cerebral ventricle were completely ineffective on epileptiform activity (P<0.01) . These findings suggest that NO may be an endogenous antiepileptic substance.

J Am Chem Soc, 2001 Aug 8, 123(31), 7574 - 83
A theoretical study of the aminolysis reaction of lysine 199 of human serum albumin with benzylpenicillin: consequences for immunochemistry of penicillins; Diaz N et al.; Herein, we present results of a computational study on benzylpenicillin attachment to Lys199 of human serum albumin via an aminolysis reaction . The internal geometry of the reactive part of the system was taken from previous work at the B3LYP/6-31+G* level on the water-assisted aminolysis reaction of a penicillin model compound (Diaz, N.; Suarez, D.; Sordo, T . L . J . Am . Chem . Soc . 2000, 122, 6710--6719) . The protein environment around Lys199, the 6-acylamino side chain, and the 2-methyl groups of benzylpenicillin were relaxed by carrying out geometry optimizations with a hybrid QM/MM method (PM3/AMBER) . Two different mechanistic routes were explored: a one-step water-assisted process and a carboxylate and water-assisted route in which the beta-lactam carboxylate and the ancillary water molecule mediate the proton transfer from the epsilon-amino group of Lys199 to the beta-lactam leaving N atom . The corresponding energy profiles in the protein combine the B3LYP/6-31+G* and PM3 energies of the reactive subsystem (benzylpenicillin + Lys199 side chain + the ancillary water molecule) and semiempirical PM3 energies of the entire system evaluated with a "divide and conquer" linear-scaling method . It is observed that penicillin haptenation to HSA can proceed through the water-assisted concerted mechanism which is calculated to have a high energy barrier of approximately 38 kcal/mol, in agreement with the experimentally observed slow reaction kinetics.

Nervenarzt, 2001 Jul, 72(7), 546 - 8
{Hoigne syndrome . Case report and current literature review}; Schreiber W et al.; Hoigne's syndrome is currently considered a pseudoanaphylactic or pseudoallergic reaction following intramuscular and aqueous procaine penicillin administration . This disorder is characterized predominantly by neuropsychiatric alterations including severe psychomotor agitation with confusion, sensations of disintegration, depersonalization, and derealization, perceived changes of body shape, visual and auditory hallucinations, panic-like anxiety including fear of death as well as alterations of consciousness and seizures . Beside the "classic" immediate manifestation of Hoigne's syndrome, subacute forms as well as reactions of the so-called latent type are also known . Including a typical case report, we present a review of the currently available literature concerning clinical picture, hypotheses on origin, and possible therapy regimens of this underdiagnosed complication of antibiotic penicillin treatment.

J Chromatogr A, 2001 Jul 6, 921(2), 147 - 60
Immobilized penicillin G acylase as reactor and chiral selector in liquid chromatography; Massolini G et al.; In this paper, the use of penicillin G acylase (PGA) as a biocatalyst and as a chiral selector is described . Penicillin G-acylase is an interesting enzyme used in the manufacture of semisynthetic antibiotics and, in particular, in the production of 6-APA by hydrolysis of penicillin G . Five PGA-based HPLC columns have been prepared by using two different silica supports by employing two immobilization methods, namely "in situ" and "in batch" . The effects of the immobilization techniques and of different silica pore size on the catalytic properties of the enzyme as well as the applicability of the PGA-bonded stationary phases as chiral selectors for a number of chiral drugs have been investigated . The HPLC columns based on immobilized PGA combine the hydrolytic activity and the chiral recognition properties of PGA, therefore they have been used for the development of a combined reaction-separation system for chiral and achiral substrates.

Seizure, 2001 Jun, 10(4), 269 - 78
Autonomic nervous system activity and life threatening arrhythmias in experimental epilepsy; Mameli O et al.; In the present study the possible derangement of the autonomic system and its influence in life threatening arrhythmias were analysed during paroxysmal activity . In hemispherectomized rats a paroxysmal activation of the hypothalamic and mesencephalic cardioarrhythmogenic triggers was performed by topical application of penicillin-G . Blood gas parameters and electrical activity of the thalamus, hypothalamus, vagal nerve fibre, ECG and arterial blood pressure were simultaneously monitored in basal conditions and repeated after the appearance of paroxysmal activity . Temporal correlation analysis was carried out . Results showed that during activation of these triggers, the spontaneous vagal nerve fibre activity significantly increased and triggered the appearance of cardiac arrhythmias which could become life threatening and induce animal death when blood gas and electrolytic parameters were simultaneously impaired . These experiments suggest that fatal evolution of the heart impairment is related not only to an autonomic cardiac trigger, but also to a concomitant metabolic derangement, which most likely shares the same autonomic origin .

Pediatr Int, 2001 Jun, 43(3), 276 - 80
Evaluation of DNA damage using the comet assay in children on long-term benzathine penicillin for secondary prophylaxis of rheumatic fever; Dundaroz R et al.; BACKGROUND: Benzathine penicillin is the most widely used antibiotic in the prophylaxis of children with rheumatic fever . The aim of the present study was to evaluate the DNA damage in children receiving one dose of 1.2 million units benzathine penicillin every 4 weeks over a long period to prevent recurrences of rheumatic fever . METHODS: Thirty-five children with confirmed rheumatic fever under benzathine penicillin prophylaxis were enrolled in the study and 35 healthy children with similar ages and socioeconomic backgrounds served as controls . To detect any DNA damage, the comet assay was performed on circulating lymphocytes from the study subjects . RESULTS: Damaged (limited and extensive migration) cells in children on prophylactic therapy were higher than those in controls (P<0.001) . CONCLUSIONS: It has been suggested that differences in the comet scores were induced by the administration of benzathine penicillin over a long period of time and further investigations are needed to confirm this toxic effect.

Neurosci Res, 2001 Aug, 40(4), 325 - 36
Long-term change in synaptic transmission in CA3 circuits followed by spontaneous rhythmic activity in rat hippocampal slices; Nakashima K et al.; The relevance of long-term potentiation (LTP) at excitatory synapses in CA3 circuits to generation of spontaneous epileptiform bursts in CA3 was investigated using rat hippocampal slices . CA3 pyramidal cells were antidromically stimulated through Schaffer collaterals . Evoked field potentials were extracellularly recorded from the stratum pyramidale and the stratum radiatum in CA3 . Therefore, field potentials reflecting recurrent excitatory post-synaptic potentials (EPSPs) and inhibitory post-synaptic potentials (IPSPs) were positive at the stratum pyramidale and negative at the stratum radiatum . First, we tested how the amplitude of the evoked field potentials depends on a gamma-aminobutyric acid (GABA(A)) antagonist . Both of the positive and negative field potential peaks reduced in the medium containing penicillin (2 mM) or bicuculline (20 microM) . This suggests that unmasked EPSPs due to suppression of IPSPs do not result in an increase in the evoked potentials . Second, CA3 pyramidal cells were antidromically stimulated by tetanic stimulation of Schaffer collaterals in order to induce LTP at synapses in CA3 circuits . Both of the positive and negative field potentials increased, suggesting that recurrent EPSPs were enhanced by tetanic stimulation . Induction of LTP at recurrent excitatory synapses was followed by spontaneous epileptiform bursts which persisted throughout experiments (approximately 1.5 h), while LTP of afferent synaptic potential evoked by hilar test stimulation was not induced . These results suggest that LTP at the afferent synapses is not necessary to spontaneous epileptiform bursts in CA3, but LTP at excitatory synapses between CA3 pyramidal cells contribute to spontaneous epileptiform bursts.

Appl Biochem Biotechnol, 2001 May, 94(2), 127 - 34
Single-Step purification and immobilization of penicillin acylase using hydrophobic ligands; Adikane HV et al.; Five different hydrophobic ligands immobilized on 4% (4XL) and 6% (6XL) crosslinked agarose were used to study the single-step purification of penicillin acylase from cell lysate . The 4XL gels showed relatively higher specific activity and recovery than the 6XL gels . In single-step purification, highly active enzyme (42 U/mg) was obtained using moderately hydrophobic ligand (octyl) . The crude enzyme immobilized on octyl gel by adsorption showed significant operational stability over a period of 30 d at room temperature . Reactor studies demonstrated the feasibility of hydrophobic ligands as a medium for immobilization.

Indian Heart J, 2001 Jan-Feb, 53(1), 25 - 34
Can we eradicate rheumatic fever in the 21st century?
Stollerman GH.
In the latter half of the 20th century, the clinical importance of variation in the virulence of strains of GAS has been clearly demonstrated . Although still obscure, the pathogenesis of ARF requires immunologically significant infection of the throat by virulent GAS strains . These strains contain large hyaluronate capsules and large M-protein molecules . The latter contain epitopes cross-reactive with host tissues, and also contain superantigenic toxic moieties . In areas where ARF has become rare, GAS pharyngitis continues to be common but is caused predominantly by GAS strains of relatively low virulence . These, however, may colonize the throat avidly and stubbornly . Molecularly distinct pyoderma strains may cause acute glomerulonephritis, but they are not rheumatogenic even though they may secondarily infect the throat . In developing countries with a very high incidence of rheumatic heart disease, identification of the prevalent rheumatogenic GAS strains and development of a multivalent vaccine against them is currently an interesting strategy . Pending vaccine development, intense primary and secondary penicillin prophylaxis should continue to be sharply focused on populations with the highest prevalence of RHD as such measures may often succeed in driving away the most virulent rheumatogenic clones of GAS from their midst.

J Agric Food Chem, 2001 Jul, 49(7), 3349 - 55
Generation of class-selective monoclonal antibodies against the penicillin group; Cliquet P et al.; To develop a penicillin-specific ELISA, different attempts were made to obtain monoclonal antibodies specific for the common structure of penicillins . Ampicillin was coupled to different carrier proteins (bovine serum albumin, chicken ovalbumin, and thyroglobulin) to render it immunogenic . Different coupling methods were compared: two methods using a cross-linker (glutaraldehyde or a succinimide ester), one carbodiimide-mediated coupling method, and one method without any cross-linker or mediator molecule (physiological binding) . Mice were immunized with the conjugates intraperitoneally or in the footpad . A screening ELISA was developed to detect anti-ampicillin antibodies in sera . Specificity and affinity of the antibodies were demonstrated by inhibiting their binding with a 10 mM solution of ampicillin . No difference could be observed using electrofusion or PEG-mediated fusion . For the production of the monoclonals, an intravenous final boost gave antibodies with better specificity and affinity than an intraperitoneal final booster injection . At least one anti-ampicillin monoclonal antibody (19C9) cross-reacts with penicillin G, oxacillin, dicloxacillin, and carbenicillin, and not with sulfanilamide, chloramphenicol, neomycin, and streptomycin, and is therefore considered interesting for developing a penicillin-specific ELISA.

J Neurosurg Spine, 2001 Jul, 95(1), 132 - 4
Cervical epidural actinomycosis . Case report; Eftekhar B et al.; Cervical actinomycosis causing spinal cord compression is a rare clinical entity . In a review of the literature, the authors found only 13 cases with actinomycosis-related spinal neurological deficit . The authors describe the case of a 26-year-old man who presented with neck pain and partial paresis of the upper limbs . Magnetic resonance imaging revealed a long cervical epidural enhancing lesion that extended from C-1 to T-2 . The radiological findings resembled metastasis and other epidural infections . The patient was treated medically with penicillin and amoxicillin for 7 months and recovered neurologically . The authors conclude that although cervical epidural actinomycosis is a rare clinical entity resembling metastasis and other infections in this region, it should be considered so that this unique infection can be diagnosed in the least invasive fashion and, whenever possible, unnecessary surgery can be avoided.

Cell Biol Int, 2001, 25(7), 593 - 8
Direct nitric oxide imaging in cultured hippocampal neurons with diaminoanthraquinone and confocal microscopy; Chen X et al.; A method for the direct measurement of intracellular nitric oxide (NO) production stimulated by penicillin G (PG) in cultured hippocampal neurons with diaminoanthraquinone (DAA) using laser scanning confocal microscopy (LSCM) was developed . Intracellular DAA fluorescence could specifically represent NO production based on two facts: (1) 3-morpholinosydnonimine, a NO donor, could dose-dependently increase DAA fluorescence; and (2) haemoglobin, a NO scavenger, could inhibit the increase of DAA fluorescence . The PG dose-dependently increased the intercellular level of glutamate (Glu, 5 min after stimulation) and the intracellular NO production (30 min throughout stimulation) . The increase of NO production could be reversed by N(w)-nitro- l -arginine (a NO synthase inhibitor), and also by d (-)2-amino-5-phosphonovaleric acid, a subtype of Glu receptor antagonist . These results revealed that DAA could be used to indicate real-time and kinetic intracellular NO production of hippocampal neurons with higher sensitivity, specificity and accuracy .

J Vet Pharmacol Ther, 2001 Jun, 24(3), 161 - 9
Bioavailability and disposition of sodium and procaine penicillin G (benzylpenicillin) administered orally with milk to calves; Musser JM et al.; Eighteen 1-week-old Holstein calves were randomly assigned to one of three groups: (a) sodium penicillin G administered intravenously, (b) sodium penicillin G administered orally, or (c) procaine penicillin G administered orally . All calves were dosed with penicillin G at 4.0 mg/kg BW . At 5 weeks of age, the calves were dosed again . Blood samples were taken serially for 24 h after both dosings . Plasma was assayed for penicillin G by high performance liquid chromatography (HPLC) . For i.v . administration, the area under the concentration-time curve (AUC), 7456 and 5508 ng/mL h, and systemic clearance, 0.54 and 0.73 L/kg h, were significantly different (P < 0.05) at 1 and 5 weeks of age, respectively . There were no significant differences between orally administered sodium and procaine penicillin G within the same age groups . Following oral (p.o.) administration, there were significant differences (P < 0.01) at 1 and 5 weeks of age in the AUC, 760 and 409 ng/mL h, terminal half-life, 2.1 and 1.6 h, time of maximum concentration (TMAX), 3.0 and 2.3 h, and maximum plasma concentration (CMAX), 85 and 58 ng/mL, respectively . Bioavailability was 10.2 and 7.4% at 1 and 5 weeks, respectively.

J Basic Microbiol, 2001, 41(2), 67 - 73
Penicillin productivity and glutathione-dependent detoxification of phenylacetic and phenoxyacetic acids in Penicillium chrysogenum; Emri T et al.; Both toxicity and penicillin productivity of the hydroxylated derivatives of phenylacetic acid (PA) and phenoxyacetic acid (POA) were highly dependent on the position of hydroxylation on the aromatic ring in Penicillium chrysogenum . Hydroxylation at position 2 diminished penicillin production but the compounds retained most of their toxicity . On the other hand, hydroxylation at position 4 resulted in barely toxic derivatives with still significant penicillin productivity . 3-Hydroxy-PA was a weak side-chain precursor with considerably reduced toxicity . The activity of the glutathione-dependent detoxification pathway correlated well with the toxicity of the compounds but there was no correlation between acidity, toxicity and penicillin productivity.

Clin Infect Dis, 2001 Aug 1, 33(3), 354 - 63 Epub 2001 Jun 25.
Pathogenesis of maternal-fetal syphilis revisited; Wicher V et al.; Although congenital syphilis has been recognized for several centuries and an efficient treatment with penicillin became available more than a half-century ago, the disease is still with us . Inability to culture in vitro the causative agent, Treponema pallidum, and the lack of an adequate animal model have prevented exploration of the various immunopathological events affecting the natural course of congenital infection . The purpose of this review is to analyze the disease in the context of recent knowledge acquired from human and experimental animals, particularly from the guinea pig model of congenital and neonatal syphilis, and to describe how the infection interacts with the maternal-fetal unit and how it is further modulated by the conceptus' ontogenic development . We also attempt to elucidate several old immunologic concepts and misconceptions that have remained unchallenged for too long.

Cell Mol Life Sci, 2001 May, 58(5-6), 835 - 43
Probing the penicillin sidechain selectivity of recombinant deacetoxycephalosporin C synthase; Dubus A et al.; Deacetoxycephalosporin C synthase from Streptomyces clavuligerus catalyses the conversion of the five-membered penicillin ring to the unsaturated six-membered cephem ring of deacetoxycephalosporin C . The effects on enzyme activity of the penicillin substrate sidechain and various cofactors were investigated using a continuous spectrophotometric assay . The conversion of penicillin G to phenylacetyl-7-aminodeacetoxycephalo sporanic acid (G-7-ADCA) was confirmed, and further details of the reaction were elucidated . The conversion of ampicillin to cephalexin was faster than that of acetyl-6-APA to acetyl-7-ADCA kcat = 0.120 +/- 0.001 s(-1) versus 0.035 +/- 0.001 s(-1), but they had similar Km values: 4.86 +/- 0.12 and 3.28 +/- 0.26 mM, respectively . Amoxycillin and penicillin V were also converted at low levels . Conversion was not detected for penicillanate, 6-aminopenicillanate, carbenicillin, temocillin, ticarcillin or benzylpenicilloic acid, suggesting that the enzyme has a relatively strict selectivity for the sidechain of the penicillin substrate.

Saudi Med J, 2000 Aug, 21(8), 771 - 4
Actinomycotic liver abscess; Al-Khuwaitir TS et al.; Actinomycosis bacteria are known for their disregard to anatomical boundaries and their ability to infect organs all over the body including the liver . Here the infection is usually contained in the form of single or multiple abscesses . The clinical manifestations produced are variable even protean and only in some patients point to the right upper abdominal quadrant . However with appropriate imaging modalities and culture techniques for microaerophilic organisms accurate diagnosis is possible and specific antibiotic therapy can be initiated . We report a patient with an actinomycotic liver abscess and no apparent predisposing factor . She was diagnosed on the basis of a history of fever and right upper quadrant pain and tenderness, the abdominal ultrasound and computed tomography findings of a hypodense liver lesion and a histopathology specimen following a diagnostic and therapeutic aspiration of the liver abscess, and had an excellent response to penicillin therapy which demonstrates the nowadays possible avoidance of laparoscopic, and open surgical intervention for this condition.

Allergy, 2001 Jul, 56(7), 611 - 8
In vitro T-cell responses to beta-lactam drugs in immediate and nonimmediate allergic reactions; Luque I et al.; BACKGROUND: beta-Lactam drugs may induce both cellular and humoral allergic reactions, and there is evidence that T cells play an important role in the pathogenesis of these reactions . The aim of this work was to assess the sensitivity and specificity of the lymphocyte transformation test (LTT) as an in vitro diagnostic tool, in patients with either an immediate or a nonimmediate reaction to penicillin G and/or amoxicillin . METHODS: Fifty patients with a well-documented history of allergic reactions to beta-lactams (31 immediate and 19 nonimmediate) were studied by means of skin tests (prick and intradermal), radioallergosorbent test (RAST), and, when necessary, controlled administration of the drug . Twenty-eight healthy subjects with good tolerance to penicillins served as controls . LTT was performed in all subjects . RESULTS: Skin tests were positive in 77.4% of the patients with immediate reactions and in 36.8% of those with nonimmediate reactions . The overall sensitivity of LTT in the allergic patients was 62%, but, when analyzed separately, sensitivity was 64.5% for the immediate group and 57.9% for the nonimmediate group . The LTT specificity was 92.8% . CONCLUSION: The LTT should be considered a useful in vitro diagnostic tool to identify subjects allergic to penicillins, especially patients with nonimmediate reactions where the LTT has a better diagnostic value than skin tests . Interestingly, positive T-cell proliferative responses can be observed 10 or more years after the occurrence of the reaction without further exposure to the drug.

J Bacteriol, 2001 Jul, 183(14), 4115 - 26
Constitutive septal murein synthesis in Escherichia coli with impaired activity of the morphogenetic proteins RodA and penicillin-binding protein 2; de Pedro MA et al.; The pattern of peptidoglycan (murein) segregation in cells of Escherichia coli with impaired activity of the morphogenetic proteins penicillin-binding protein 2 and RodA has been investigated by the D-cysteine-biotin immunolabeling technique (M . A . de Pedro, J . C . Quintela, J.-V . Holtje, and H . Schwarz, J . Bacteriol . 179:2823-2834, 1997) . Inactivation of these proteins either by amdinocillin treatment or by mutations in the corresponding genes, pbpA and rodA, respectively, leads to the generation of round, osmotically stable cells . In normal rod-shaped cells, new murein precursors are incorporated all over the lateral wall in a diffuse manner, being mixed up homogeneously with preexisting material, except during septation, when strictly localized murein synthesis occurs . In contrast, in rounded cells, incorporation of new precursors is apparently a zonal process, localized at positions at which division had previously taken place . Consequently, there is no mixing of new and old murein . Old murein is preserved for long periods of time in large, well-defined areas . We propose that the observed patterns are the result of a failure to switch off septal murein synthesis at the end of septation events . Furthermore, the segregation results confirm that round cells of rodA mutants do divide in alternate, perpendicular planes as previously proposed (K . J . Begg and W . D . Donachie, J . Bacteriol . 180:2564-2567, 1998).

Chem Res Toxicol, 2001 Jun, 14(6), 694 - 701
Indirect cytotoxicity of flucloxacillin toward human biliary epithelium via metabolite formation in hepatocytes; Lakehal F et al.; Flucloxacillin, an isoxazolyl-penicillin, causes cholestasis and biliary epithelium injury . The aim of the study was to determine whether flucloxacillin, either directly or through metabolite formation, may induce cytotoxicity in hepatic or biliary cells . Cytotoxicity was assessed by lactate dehydrogenase release in primary cultures of human hepatocytes and of gallbladder-derived biliary epithelial cells (BEC) . Metabolite production in microsome and cell preparations was analyzed by chromatography, nuclear magnetic resonance spectroscopy, and mass spectrometry . While flucloxacillin induced no direct cytotoxicity in any of the hepatocyte (n = 12) and BEC (n = 19) preparations, the conditioned media from cultured hepatocytes preincubated with flucloxacillin (50-500 mg/L) triggered a significant increase in lactate dehydrogenase release over controls in approximately 50% of BEC preparations (7/12), and this effect depended upon flucloxacillin concentration . Remaining BEC preparations exhibited no toxic response . Cytotoxicity in BEC preparations (9/13) was also induced by the supernatants of human liver microsomes and of recombinant human cytochrome P450 (CYP)3A4 preincubated with flucloxacillin (500 mg/L) . Supernatants from both liver microsome and CYP3A4 preparations contained one major metabolite which was identified as 5'-hydroxymethylflucloxacillin . The production of this metabolite was inhibited following CYP3A4 inhibition by troleandomycin in human liver microsomes, and markedly enhanced following CYP3A induction by dexamethasone in rat liver microsomes . As opposed to BEC, cultured hepatocytes displayed significant CYP3A activity and produced low amounts of this metabolite . The purified metabolite (0.01-5 mg/L) exerted toxic effects in BEC but not in hepatocytes . In conclusion, hepatocytes mainly via CYP3A4 activity, generate flucloxacillin metabolite(s) including 5'-hydroxymethylflucloxacillin that may induce cytotoxicity in susceptible BEC . These metabolic events may contribute to the pathogenesis of drug-induced cholangiopathies.

MMWR Morb Mortal Wkly Rep, 2000 Aug 18, 49(32), 729 - 31
Update: newborn screening for sickle cell disease--California, Illinois, and New York, 1998; On the excited-state energy transfer between tryptophan residues in proteins: the case of penicillin acylase; TUBITAK Marmara Research Center, RIGEB, Gebze-Kocaeli, TurkeyThe problem, whether excited-state energy transfer occurs between Trp residues in a multi-tryptophan proteins and if it does, what kind of changes it induces in different parameters of protein fluorescence, is currently under active investigation . In our previous paper {Biophys . Chem . 72 (1998) 265}, the energy transfer was found and studied in detail for Na,K-ATPase . It was shown that this transfer influences all parameters of fluorescence emission, which is detected at site-selective conditions (red-edge of excitation, blue and red edges of emission) . Present experiments were performed on unusually tryptophan-rich protein, bacterial penicillin acylase (28 Trp per dimer of 82 kDa) and were aimed to extend these observations . They demonstrate substantial heterogeneity in the environments of tryptophan residues within the protein structure . This suggests, that in the present case, if the energy transfer exists, it should be directed from short-wavelength-emitting to long-wavelength-emitting tryptophan residues and thus could be easily observed by a number of time-resolved and steady-state fluorescence techniques . Unexpectedly, no signature of inter-tryptophan energy transfer was found.

J Am Vet Med Assoc, 2001 May 15, 218(10), 1619 - 23, 1582
Otitis media in a llama; Koenig JB et al.; A 7-month-old female llama was examined because of chronic otitis media and externa of 7 months' duration . Radiographically, the tympanic bullae appeared thicker than normal, and the ventral borders were poorly defined; the left external acoustic meatus (ear canal) appeared to be narrower than the right . The llama was treated with penicillin, and the ear canals were lavaged daily . Contrast radiography was performed on day 15 to determine the shape and size of the ear canals and evaluate the integrity of the tympanic membranes . Contrast medium was visible radiographically in the left tympanic bulla, indicating that the left tympanic membrane was ruptured, but the right tympanic membrane appeared to be intact . The left ear canal was narrower than the right, and the bony ear canals had a well-defined sigmoid shape . The right ear improved with medial treatment alone, but the left ear did not . Therefore, lateral ear canal resection was performed . After surgery, however, exudate was still evident in the left ear canal, and the llama became more lethargic and more reluctant to eat . Lateral bulla osteotomy was attempted, but no purulent material was obtained, and curettage of the bulla resulted in hemorrhage . Because of this and because of the llama's poor physical condition, a decision was made to euthanatize the llama . The sigmoid shape of the bony ear canal and the multicompartmental nature of the tympanic bulla make surgical treatment of otitis media and externa in llamas difficult . Further study of surgical treatments for otitis media in llamas is needed.

Biosens Bioelectron, 2001 Jun, 16(4-5), 277 - 86
A novel microphysiometer based on MLAPS for drugs screening; Yicong W et al.; This paper presents a novel microphysiometer for simultaneous measurements of several extracellular ions concentrations in living cells based on MLAPS (multi-light addressable potentiometric sensor) . In the microphysiometer, different sensitive membranes are illuminated in parallel with n light sources at different frequencies, the response amplitudes of each frequency component can be measured on-line by parallel processing algorithm . By the experiments, we can analyze the relations of the extracellular environmental H(+), Na(+), K(+), Ca(2+) under the effects of western medicines (dilantin, phenobarbital sodium, penicillin sodium) and Chinese drugs (scutellaria, medlar, hemlock parsley), and estimate the effects of several drugs . As the novel microphysiometer works under regular cell culture conditions, cells can be repeatedly simulated with drugs to complete dose-response curve within a few hours . With the detection of a general parameter (extruded protons and ions), the system can be used to monitor the real-time process of the cells' metabolism, observe the functional responses of different kinds of membrane-bound receptors, evaluate the drugs.

Obstet Gynecol, 2001 Jun, 97(6), 947 - 53
Fetal syphilis: clinical and laboratory characteristics; Hollier LM et al.; OBJECTIVE: To examine the pathophysiology of fetal syphilis and correlate hematologic, immunologic, and sonographic findings . METHODS: Twenty-four women with untreated syphilis during pregnancy were prospectively identified . Sonography with amniocentesis and percutaneous umbilical blood sampling were performed . Darkfield examination, rabbit infectivity testing, and polymerase chain reaction for detection of Treponema pallidum were performed on amniotic fluid . Hematologic and chemical testing of fetal blood was performed using standard techniques . Fetal antitreponemal IgM was detected by Western blot assay . Maternal syphilis was treated with 2.4 to 4.8 million units of benzathine penicillin G intramuscularly . Neonatal outcomes and signs of congenital syphilis were recorded . RESULTS: Six women had primary, 12 had secondary, and six had early latent syphilis . Sixty-six percent of fetuses (95% confidence interval {CI} 47%, 82%) had either congenital syphilis or detection of Treponema pallidum in amniotic fluid . Sixty-six percent had hepatomegaly, including three fetuses (12.5%, 95% CI 4%, 31%) with ascites . Fetal antitreponemal IgM was detected in three cases . Abnormal liver transaminases were found in 88% (CI 69%, 96%), anemia in 26% (CI 13%, 47%), and thrombocytopenia in 35% (CI 19%, 55%) . Maternal treatment was successful in 83% (CI 64%, 93%) . Risk of treatment failure was significantly increased when hepatomegaly and ascites were present (P =.01) . CONCLUSION: Findings with fetal syphilis are similar to those of neonatal syphilis . We hypothesize that fetal transaminase elevation occurs early in the course of infection; hematologic abnormalities and hydrops occur later . Severity of disease may be associated with risk of treatment failure.

Prog Neuropsychopharmacol Biol Psychiatry, 2001 May, 25(4), 709 - 27
Pharmacotherapy of mental illness--a historical analysis; Ban TA; The history of pharmacotherapy of mental illness can be divided into three periods . Introduction of morphine, potassium bromide, chloral hydrate, hyoscine, paraldehyde, etc., during the second half of the 19th century (first period), led to the replacement of physical restraint by pharmacological means in behavior control . Introduction of nicotinic acid, penicillin, thiamine, etc., during the first half of the 20th century (second period), led to significant changes in the diagnostic distribution of psychiatric patients; psychoses due to cerebral pellagra, and dementia due to syphilitic general paralysis virtually disappeared from psychiatric hospitals, and the prevalence of dysmnesias markedly decreased . Treatment with therapeutically effective drugs of mania, schizophrenia, depression, bipolar disorder, generalized anxiety disorder, panic disorder, obsessive compulsive disorder, Alzheimer's disease, etc., during the second half of the 20th century (third period), brought to attention the heterogeneity of the populations within the diagnostic categories of schizophrenia and depression . Introduction of the first set of psychotropics and the spectrophotofluorimeter during the 1950s triggered the development of neuropsychopharmacology . Introduction of genetic technology for the separation of receptor subtypes in the 1980s opened the path for the "tailoring" of psychotropic drugs by the dawn of the 21st century, to receptor affinities.

Int J Pediatr Otorhinolaryngol, 2001 Jun 7, 59(2), 119 - 23
Short-term penicillin-V prophylaxis did not prevent acute otitis media in infants; Fogle-Hansson M et al.; OBJECTIVE: To determine whether prophylactic, short-term penicillin V treatment during upper respiratory tract infections can prevent the occurrence of recurrent acute otitis media in young children . METHODS: Seventy children were studied in a prospective, double-blind, placebo-controlled study . All children had suffered their first episode of acute otitis media before the age of 6 months . After inclusion in the study group, administration of penicillin V or placebo was initiated by the parents at subsequent upper respiratory tract infections . The children were examined by otomicroscopy within 3 days after treatment was initiated . The children were scheduled for a total follow-up period of 12 months, including bimonthly visits for check-up irrespective of treatment periods . RESULTS: There were 304 treated episodes of upper respiratory tract infection . There was no significant difference in the number of acute otitis episodes between groups . CONCLUSION: Initiation of penicillin V prophylaxis at upper respiratory tract infection in small children did not prevent recurrent acute otitis media in this study.

Int J Pharm, 2001 Jun 4, 220(1-2), 33 - 41
Microwave-enhanced dehydration and solvent washing purification of penicillin G sulfoxide; Pan X et al.; In the present study, a new microwave-enhanced dehydration and solvent washing purification of penicillin G sulfoxide technique has been developed . The results show that microwave irradiation can dehydrate penicillin G sulfoxide from a water content of 14-26 to below 0.5% in 40-60 min in N2 or air . After washing with ethyl acetate to remove impurities and residual water, the penicillin G sulfoxide can be used to synthesize cephalosporanic acid . The recovery of cephalosporanic acid was equal to and the purity of cephalosporanic acid was higher by 2% than that of the current dehydration technique . FTIR spectroscopy was used to study the process of microwave-enhanced dehydration and solvent washing purification of penicillin G sulfoxide.

ANZ J Surg, 2001 May, 71(5), 285 - 9
Management of extravasation injuries; Kumar RJ et al.; BACKGROUND: Various agents have been implicated in causing tissue necrosis after intravenous infusions have extravasated . These include solutions of calcium, potassium, bicarbonate, hypertonic dextrose, cytotoxic drugs and antibiotics . Views on management of these injuries differ, and range from a non-operative conservative approach to early debridement and grafting . METHODS: A retrospective review was undertaken of the hospital files of patients with extravasation injuries seen in three Australian hospitals . Nine patients were identified, and their management and long-term follow up are reported . RESULTS: Age ranged from 17 days to 60 years . Two patients received their injuries from solutions containing isotonic dextrose/saline . The other seven patients received injuries from a variety of solutions including calcium gluconate (n = 1), parenteral nutrition (n = 1), sodium bicarbonate (n = 1), immunoglobulin (n = 1), gentamicin and penicillin (n = 1), flucloxacillin (n = 1), and the chemotherapeutic agents epirubicin and cyclophosphamide (n = 1) . The sites involved included the dorsum of the right foot (n = 3), the dorsum of the left foot (n = 3), the right groin (n = 1), the right hand (n = 1) and the left hand (n = 1) . Four patients were managed by delayed debridement and split skin grafting, while five were treated non-operatively . Prolonged scar management was necessary in seven of the nine patients . Final results were satisfactory in all patients who received skin grafting and in all patients who were managed conservatively . CONCLUSIONS: Management of extravasation injuries should be conservative if possible . Delayed debridement and split skin grafting is required if the area of skin loss is extensive . Scar management remains a problem . Prevention of these injuries with the education of both medical and nursing staff remains the ultimate aim.

JAMA, 2001 May 16, 285(19), 2498 - 505
The rational clinical examination . Is this patient allergic to penicillin? An evidence-based analysis of the likelihood of penicillin allergy; Salkind AR et al.; CONTEXT: Clinicians frequently withhold antibiotics that contain penicillin based on patients' self-reported clinical history of an adverse reaction to penicillin and the clinicians' own misunderstandings about the characteristics of a true penicillin allergy . OBJECTIVES: To determine the likelihood of true penicillin allergy with consideration of clinical history and to evaluate the diagnostic value added by appropriate skin testing . DATA SOURCES: MEDLINE was searched for relevant English-language articles dated 1966 to October 2000 . Bibliographies were searched to identify additional articles . STUDY SELECTION: We included original studies describing the precision of skin testing in diagnosis of penicillin allergy . We excluded studies that did not use both minor and major determinants, provide an explicit definition of penicillin allergy, or list the specific criteria necessary for a positive skin test result . Fourteen studies met the inclusion criteria . DATA EXTRACTION: Three authors independently reviewed and abstracted data from all articles and reached consensus about any discrepancies . DATA SYNTHESIS: Patients' self-reported history has low accuracy for diagnosis of true penicillin allergy . By evaluating studies comparing clinical history to the skin test for penicillin allergy among patients with and without a positive history for penicillin allergy, positive and negative likelihood ratios were calculated . History of penicillin allergy had a positive likelihood ratio of 1.9 (95% confidence interval {CI}, 1.5-2.5), while absence of history of penicillin allergy had a negative likelihood ratio of 0.5 (95% CI, 0.4-0.6) . CONCLUSIONS: Only 10% to 20% of patients reporting a history of penicillin allergy are truly allergic when assessed by skin testing . Taking a detailed history of a patient's reaction to penicillin may allow clinicians to exclude true penicillin allergy, allowing these patients to receive penicillin . Patients with a concerning history of type I penicillin allergy who have a compelling need for a drug containing penicillin should undergo skin testing . Virtually all patients with a negative skin test result can take penicillin without serious sequelae.

Sheng Li Xue Bao, 1998 Oct, 50(5), 507 - 13
{Effect of nitric oxide release on epileptiform discharge in CA1 area of hippocampal slices}; Lu W et al.; Using a nitric oxide (NO)-sensitive platinum microelectrode (SNM) modified with chitosan nickel (II) complex and Nafion (Nafion-CTS (Ni)-Pt), we observed the effect of nitric oxide synthase (NOS) inhibitor 7-nitro-indazole (7-NI) and N omega-nitro-L-arginine (L-NNA) on penicillin-treated hippocampal slices by simultaneously recording the stimulus-evoked field potentials and nitric oxide release from CA1 pyramidal neurons . Our results show: (1) The linear relationship range and detection limit of SNM were 4.5 x 10(-4)-1.0 x 10(-8) mol/L and 5.0 x 10(-8) mol/L respectively . (2) Penicillin (PEN) could elevate NO release, the number and amplitude of stimulus-evoked field potentials spike (SEPS) in concentration-dependent manner; (3) Both 7-NI and L-NNA depressed NO release and partly reversed the effect of penicillin . The above findings suggest that convulsant provoking effect of NO could be inhibited by NOS inhibitors . The NO-sensitive electrode may provide an useful tool for continuous detection of NO in biological tissues.

J Int Assoc Physicians AIDS Care, 1997 Jan, 3(1), 27 - 8
Historical perspective: Nuremberg, Tuskegee, and the radiation experiments; Chadwick GL; AIDS: The National Research Act was passed as a result of the Tuskegee Study, a research study investigating syphilis in black males who received no treatment despite the discovery of penicillin . The Act requires the publication of regulations for the protection of human subjects, as well as requirements for informed consent and review of research by institutional research boards . The 1975 Declaration of Helsinki was also revised . President Clinton, spurned on by reports of humans unknowingly being injected with plutonium for research purposes, created the Advisory Committee on Human Radiation Experiments . The Committee's report culminated in the creation of the National Bioethics Advisory Commission to act as a national deliberative body to advise on the ethical issues faced by the research community today . Despite codes, regulations, and policies, the ultimate protection of research subjects and the future of the research enterprise itself rests with individual investigators and their sense of ethical behavior in fulfilling their obligations to their research subjects .

AIDS Patient Care STDS, 1998 Dec, 12(12), 921 - 5
Malignant syphilis: a review; Kumar B et al.; Syphilis is a disorder that may mimic many other diseases . Its incidence has risen and fallen over the centuries . A particularly malignant and virulent form, lues maligna, has recently been more frequently observed in the HIV-infected population . Raising the awareness of the occurrence of and the clinical and laboratory criteria of syphilis in general and lues maligna in particular in the HIV-infected population is becoming more urgent . Early treatment can result in a good outcome and stem the spread of the disease; as with other forms of syphilis, penicillin is the drug of choice.

Clin Infect Dis, 2001 Jun 15, 32(12), 1661 - 73 Epub 2001 May 21.
Syphilitic posterior uveitis: correlative findings and significance; Ormerod LD et al.; Twenty-one patients with syphilitic posterior uveitis were investigated retrospectively to study the disease spectrum, associations with neurosyphilis, and therapeutic implications . Ophthalmologic manifestations of syphilitic posterior uveitis are differentiated into acute and chronic uveitides . The several distinct acute uveitic syndromes are usually florid and are associated with early syphilis, with VDRL-positive syphilitic meningitis, and frequently with human immunodeficiency virus coinfection . The chronic posterior uveitides are often insidious, a manifestation of late syphilis, and associated commonly with subclinical neurosyphilis . All patients with acute cases and 54% of patients with chronic cases in our study received penicillin therapy appropriate for neurosyphilis . The frequent association of syphilitic posterior uveitis with neurosyphilis and the analogous spirochetal sequestration beyond the blood-brain and the blood-ocular barriers suggest that all patients with syphilitic posterior uveitis, irrespective of ocular disease intensity, should undergo evaluation of cerebrospinal fluid and be treated with penicillin regimens appropriate for neurosyphilis.

Wiad Lek, 2001, 54(1-2), 116 - 21
{Occupational penicillin allergy as an example of chronic recurring anaphylaxis}; Kruszewski J et al.; A case of anaphylactic shock which appeared in a nurse working at surgery room for many years, was described . The nurse was examined due to the anaphylactic attack at work (paroxysmal, idiopathic anaphylaxis) . Among many factors the first of all occupational ones (exposure to disinfectants, latex and penicillin) were taken into consideration . Two minutes after the intradermal application of 2 units of crystalline penicillin the symptoms of anaphylaxis (including the shock) occurred . The problems of penicillin allergy in the aspect of skin tests, which make use of this antibiotic, were also described in the paper.

Biotechnol Bioeng, 2001 Jun 20, 73(6), 484 - 92
DegP-coexpression minimizes inclusion-body formation upon overproduction of recombinant penicillin acylase in Escherichia coli; Lin WJ et al.; We demonstrated the enhancement of recombinant penicillin acylase (PAC) production in Escherichia coli by increasing the intracellular concentration of the periplasmic protease DegP . Using appropriate host/vector systems (e.g., HB101 harboring pTrcKnPAC2902 or MDDeltaP7 harboring pTrcKnPAC2902) in which the expression of the pac gene was regulated by the strong trc promoter, the overproduction of PAC was often limited by periplasmic processing and inclusion bodies composed of protein aggregates of PAC precursors were formed in the periplasm . The amount of these periplasmic inclusion bodies was significantly reduced and PAC activity was significantly increased upon coexpression of DegP . The specific PAC activity reached an extremely high level of 674 U/L/OD(600) for MDDeltaP7 harboring pTrcKnPAC2902 and pKS12 under optimum culture conditions . However, such improvement in the production of PAC was not observed for the expression systems (e.g., MDDeltaP7 harboring pCLL2902) in which the periplasmic processing was not the step limiting the production of PAC . The results suggest that DegP could in vivo assist the periplasmic processing though the enzyme is shown to be not absolutely required for the formation of active PAC in E . coli . In addition, the steps limiting the production of PAC are identified and the reasons for the formation of PAC inclusion bodies are discussed here .

Biochim Biophys Acta, 2001 Jan 12, 1544(1-2), 386 - 92
Binding properties of human albumin modified by covalent binding of penicillin; Bertucci C et al.; Derivatisation of lysine residues in human albumin was performed in vitro by reaction with penicillin G . This modification reaction has been reported to occur in patients treated with high dosages of the antibiotic . The structure of the modified protein was characterised by mass spectrometry and circular dichroism . The number of the lysine residues involved depends on the time of incubation and on the drug/protein molar ratio . The secondary structure of the modified protein does not change significantly with respect to the native protein . Furthermore, the binding properties of the modified albumin were characterised by CD spectroscopy . Phenylbutazone, diazepam and bilirubin, known to bind to specific binding areas, were used as markers . A decrease of the affinity to the high-affinity binding sites was observed after the modification.

Vet Microbiol, 2001 Jun 6, 80(3), 247 - 53
Induction of cross-protection in mice against dolphin Erysipelothrix rhusiopathiae isolates with a swine commercial vaccine; Lacave G et al.; Erysipelothrix rhusiopathiae is well known to cause disease in dolphins . This disease occurs either in an peracute way, leading to mortality even before clinical signs are observed or in a sub-acute way, characterized by rhomboidal skin lesions, that can be treated with penicillin or its derivatives . Commercial swine vaccines, containing inactivated serotype 2 strains, are currently used for vaccination but it is not known whether these vaccines induce protection against E . rhusiopathiae isolates from dolphins . In the present study, it was demonstrated in a mouse model that vaccination with a commercial swine vaccine (Eurovac Ery, Eurovet, Belgium) containing inactivated serotype 2 E . rhusiopathiae strains induced protection against challenge with three E . rhusiopathiae isolates from dolphins . The duration of the protection varied, depending on the challenging isolate, between 8 and >23 weeks . There was however no positive correlation between the amount of antibodies at the moment of challenge and the observed protection.In conclusion, vaccination trials in mice indicate that commercial serotype 2 swine Erysipelothrix vaccines induce protection against erysipelas caused by dolphin pathogenic isolates.

Pharm Res, 2001 Jan, 18(1), 16 - 22
Characterization of the amino acid transport of new immortalized choroid plexus epithelial cell lines: a novel in vitro system for investigating transport functions at the blood-cerebrospinal fluid barrier; Kitazawa T et al.; PURPOSE: To establish and characterize a choroid plexus epithelial cell line (TR-CSFB) from a new type of transgenic rat harboring the temperature-sensitive simian virus 40 (ts SV 40) large T-antigen gene (Tg rat) . METHODS: Choroid plexus epithelial cells were isolated from the Tg rat and cultured on a collagen-coated dish at 37 degrees C during the first period of 3 days . Cells were subsequently cultured at 33 degrees C to activate large T-antigen . At the third passage, cells were cloned by colony formation and isolated from other cells using a penicillin cup . RESULTS: Five immortalized cell lines of choroid plexus epithelial cells (TR-CSFB 1 approximately 5) were obtained from two Tg rats . These cell lines had a polygonal cell morphology, expressed the typical choroid plexus epithelial cell marker, transthyretin, and possessed Na+, K+-ATPase on their apical side . TR-CSFBs cells expressed a large T-antigen and grew well at 33 degrees C with a doubling-time of 35 approximately 40 hr . {3H}-L-Proline uptake by TR-CSFB cells took place in an Na+-dependent, ouabain-sensitive, energy-dependent, and concentration-dependent manner . It was also inhibited by alpha-methylaminoisobutylic acid, suggesting that system A for amino acids operates in TR-CSFB cells . When {3H}-L-proline uptake was measured using the Transwell device, the L-proline uptake rate following application to the apical side was five-fold greater than that following application to the basal side . In addition, both Na+-dependent and Na+-independent L-glutamic acid (L-Glu) uptake processes were present in TR-CSFB cells . CONCLUSIONS: Immortalized choroid plexus epithelial cell lines were successfully established from Tg rats and have the properties of choroid plexus epithelial cells, and amino acid transport activity was observed in vivo.

Electrophoresis, 2001 Mar, 22(5), 960 - 5
Fluorescent Bocillins: synthesis and application in the detection of penicillin-binding proteins; Gee KR et al.; Novel fluorescent analogs of penicillin V were synthesized and evaluated for efficacy in the detection of penicillin binding proteins (PBPs) . These molecules include the full structure of penicillin V, with the potent Bodipy fluorophore attached to the para-position of the penicillin V phenyl group . The green fluorescent Bocillin FL and the near-infrared (IR) fluorescent Bocillin 650/665 probes were shown to bind to PBPs, both purified and from membrane preparations, with high affinity and specificity . These reagents allow for facile detection of 2-4 ng of purified PBP with the aid of a fluorescent scanner.

Cell Transplant, 2001 Mar-Apr, 10(2), 153 - 9
Comparative functional study of clonal insulin-secreting cells cultured in five commercially available tissue culture media; Hamid M et al.; The electrofusion-derived rat insulin-secreting cell line BRIN-BD11 was cultured in five different commercially available media to determine the optimum medium for the in vitro maintenance of such clonal cell lines . Cells were cultured in RPMI-1640, DMEM, McCOY'S, F-12K, or MEM culture medium supplemented with 10% (v/v) fetal bovine serum and antibiotics (100 U/ml penicillin and 0.1 g/L streptomycin) . Insulin secretion studies performed after 10 days revealed RPMI-1640 to be the best performing medium in terms of insulin secretory responsiveness to a range of stimuli including glucose, L-alanine, L-arginine, carbachol, and glibenclamide . Insulin release was significantly decreased (p < 0.01 to p < 0.05) in all other media compared to RPMI-1640 . Only the cells cultured in RPMI-1640 and DMEM showed a significant glucose-induced insulin secretory response (p < 0.01 and p < 0.05) . McCOY'S gave the next best result followed by F-12K and MEM . After the 10-day culture period, the highest insulin content was found in cells cultured in RPMI-1640 and DMEM with significantly lower levels of insulin in cells cultured in McCOY'S, F-12K, and MEM (p < 0.01 to p < 0.001) . RPMI-1640 was used for further studies to investigate the effects of 5.6-16.7 mmol/L glucose in culture on the secretory responsiveness of BRIN-BD11 cells . Significant responses to a number of nonglucidic secretagogues were seen following culture at 5.6 and 16.7 mmol/L glucose, although responsiveness was less than after culture with 11.1 mmol/L glucose . At 16.7 mmol/L glucose culture, glucose-stimulated insulin release was abolished.

J Bacteriol, 2001 May, 183(10), 3055 - 64
Contributions of PBP 5 and DD-carboxypeptidase penicillin binding proteins to maintenance of cell shape in Escherichia coli; Nelson DE et al.; Escherichia coli has 12 recognized penicillin binding proteins (PBPs), four of which (PBPs 4, 5, and 6 and DacD) have DD-carboxypeptidase activity . Although the enzymology of the DD-carboxypeptidases has been studied extensively, the in vivo functions of these proteins are poorly understood . To explain why E . coli maintains four independent loci encoding enzymes of considerable sequence identity and comparable in vitro activity, it has been proposed that the DD-carboxypeptidases may substitute for one another in vivo . We tested the validity of this equivalent substitution hypothesis by investigating the effects of these proteins on the aberrant morphology of DeltadacA mutants, which produce no PBP 5 . Although cloned PBP 5 complemented the morphological phenotype of a DeltadacA mutant lacking a total of seven PBPs, controlled expression of PBP 4, PBP 6, or DacD did not . Also, a truncated PBP 5 protein lacking its amphipathic C-terminal membrane binding sequence did not reverse the morphological defects and was lethal at low levels of expression, implying that membrane anchoring is essential for the proper functioning of PBP 5 . By examining a set of mutants from which multiple PBP genes were deleted, we found that significant morphological aberrations required the absence of at least three different PBPs . The greatest defects were observed in cells lacking, at minimum, PBPs 5 and 6 and one of the endopeptidases (either PBP 4 or PBP 7) . The results further differentiate the roles of the low-molecular-weight PBPs, suggest a functional significance for the amphipathic membrane anchor of PBP 5 and, when combined with the recently determined crystal structure of PBP 5, suggest possible mechanisms by which these PBPs may contribute to maintenance of a uniform cell shape in E . coli.

Sheng Li Xue Bao, 1998 Jun, 50(3), 355 - 8
{Changes of intracellular calcium level in hippocampal slice neurons: a confocal laser scanning microscopic study}; Wang LH et al.; In this study, the fluorescent dye Fluo-3 (AM) was applied to rat hippocampus by microinjection, to label neurons in situ . A large number of CA1 pyramidal cells could be labeled by a single injection . With this improvement of labeling and the use of the confocal laser scanning microscope (Leica Lasetechnik GmbH), changes of calcium fluorescence intensity in CA1 pyramidal cells of rat hippocampal slices on the models of mimic epilepsy (induced by penicillin or glutamate) or hypoglycemia/hypoxia were studied in vitro . The results showed that in magnesium free artificial CSF, the intracellular calcium level of the CA1 pyramidal cells increased following application of glutamate or penicillin . Similar phenomenon was also observed on the in vitro model to hypoglycemia/hypoxia.

Sheng Li Xue Bao, 1998 Aug, 50(4), 367 - 72
{The relation between changes of nitric oxide synthase in hippocampus and activities of excitatory amino acid receptor during epilepsy}; Ren JP et al.; The time course of alteration in neuronal nitric oxide synthase (nNOS) and the influence of glutamate receptor antagonists on immunoreactivity of nNOS were investigated immunohistochemically in rat hippocampus during penicillin-induced epilepsy . It was found that nNOS-like immunoreactivity in hippocampus increased at 4 h after initiation of seizure and reached a peak at 24 h . When MK-801 (6 micrograms) and DNQX (4 micrograms) were injected respectively into hippocampus 20 min before administration of penicillin, seizure was reduced in strength . Meanwhile, the nNOS-like immunoreactivity in hippocampus was decreased, compared with the group which were administered penicillin alone . These results suggest that the increase of nitric oxide may be related to the injury of neurons during and after epilepsy; the changes' of nNOS may be related to the activity of NMDA and non-NMDA receptors . Neuron protective effect of MK-801 and DNQX may be in part mediated by nNOS.

Biotechnol Bioeng, 2001 Jun 5, 73(5), 426 - 30
Highly efficient synthesis of ampicillin in an "aqueous solution-precipitate" system: repetitive addition of substrates in a semicontinuous process; Youshko MI et al.; The synthesis of ampicillin catalyzed by Escherichia coli penicillin acylase was optimized in an aqueous system with partially dissolved antibiotic nucleus 6-aminopenicillanic acid (6-APA) . The yields of both 6-APA and acyl donor could be improved by repetitively adding substrates to the reaction, allowing the concentration of 6-APA to remain saturated throughout . In this reaction concept, with four subsequent additions of substrates, 97% conversion of 6-APA and 72% of D-(-)-phenylglycine methyl ester (D-PGM) to ampicillin was achieved . The synthetic potential of this concept was estimated using a mathematical model which showed that by increasing the amount of added substrates a nearly quantitative conversion of 6-APA and 85% conversion of acyl donor into ampicillin could be achieved .

Ann Dermatol Venereol, 2001 Mar, 128(3 Pt 2), 363 - 7
{Primary and secondary hospitalization criteria}; Bernard P; The reference therapy for erysipelas is penicillin G given intravenously . Since I.V . injections are difficult to perform at home, hospitalization would seem mandatory . However, many cases of erysipelas are actually treated at home (cf . results of the 2 surveys concerning general practice) . The lack of studies on non-hospitalized erysipelas patients makes it difficult to answer the following question: "What are the criteria for primary and secondary hospitalization?" The literature suggests, mostly indirectly, that the reasons of primary hospitalization are: the severity of general (fever, impairment of general condition, confusion) or local (blisters, purpura, skin necrosis, extent of the cellulitis, facial involvement) signs and symptoms, old age, associated diseases (diabetes, alcoholism, obesity, cardiovascular disease), the practical modalities of the treatment (penicillin given intravenously, bed rest), or the necessity to eliminate deep venous thrombosis . The reasons for secondary hospitalization are above all the (true or suspected) failure of oral antibiotherapy at home, or the occurrence of local complications . True criteria of primary or secondary hospitalization remain to be defined by adequate prospective studies performed in both in and outpatients . They will depend of the emerging possibilities of successfully treating erysipelas by oral antibiotics.

Ann Dermatol Venereol, 2001 Mar, 128(3 Pt 2), 338 - 44
{Dealing with bacterial hypodermal infection in general practice: an inquiry and a prospective study}; Kopp M et al.; OBJECTIVE: The author had for aim to collect data on how general practitioners deal with bacterial hypodermal inflammation . MATERIAL AND METHODS: An enquiry on practice and a prospective study were carried out over 3 months . RESULTS: The mean number of cases reached 0.54 per physician over the 3-month period, for a total of 103 cases of bacterial hypodermal infection . The patients'mean age was slightly superior to 60 years, with a high female predominance and a preferential site of infection located in the lower limbs (89.6 p . 100 of the cases) . 20 p . 100 of the patients were immediately sent to hospital, mainly because of the importance of local and/or general symptoms, and of the underlying conditions . In home care, antibiotic therapy was almost always oral and consisted in courses of group A penicillin or pristinamycin in over half of the cases, for a mean duration of 12.4 days for erysipelas, and 9.1 days for cases classified as "other type of bacterial hypodermal infection" . An anticoagulant treatment was associated in close to 30 p . 100 of the cases, and anti-inflammatory or corticoids agents were prescribed in 17.9 p . 100 of the cases . The cure rate among home care patients reached 89.3 p . 100 and only 3 patients were hospitalized after the initial treatment; these 3 patients had all been given non-steroidal anti-inflammatory agents.

J Chromatogr B Biomed Sci Appl, 2001 Apr 15, 754(1), 135 - 40
Evaluation of immobilized metal affinity chromatography for purification of penicillin acylase; Fitton V et al.; The aim of this work was to test immobilized metal affinity chromatography (IMAC) for the purification of penicillin acylase . After evaluation of different metals, Cu2+ was selected . Different samples were tested: pure penicillin acylase, industrial clarified feedstock and crude extract . After comparing two eluents, NH4Cl and imidazole, it appeared that although both gave good results for recovery and activity, NH4Cl was a more selective eluent with a higher fold purification than imidazole (4.64 versus 2.04) . Moreover, we shown that a multistep gradient of NH4Cl, greatly increased the degree of purification (12.36) compared with the one-step process as control (4.64) . In addition, good recovery was obtained (97-100%).

Biotechnol Prog, 2001 Mar-Apr, 17(2), 294 - 303
Direct measurement of pH profiles in immobilized enzyme carriers during kinetically controlled synthesis using CLSM; Spiess AC et al.; Confocal laser scanning microscopy was applied to measure the pH value in the carrier of immobilized enzymes during the enzyme-catalyzed synthesis . pH profiles with a high resolution are shown, with the pH increasing in the core of the particles . Significant differences occur for different carrier material, particle size, porosity and surface modification . The increased pH value is identified as one of the reasons leading to reduced enzyme selectivity in the penicillin amidase catalyzed synthesis of cephalosporins and penicillins.

Mol Pharmacol, 2001 May, 59(5), 1277 - 86
Identification and characterization of human organic anion transporter 3 expressing predominantly in the kidney; Cha SH et al.; A cDNA encoding a multispecific organic anion transporter 3 (hOAT3) was isolated from a human kidney cDNA library . The hOAT3 cDNA consisted of 2179 base pairs that encoded a 543-amino-acid residue protein with 12 putative transmembrane domains . The deduced amino acid sequence of hOAT3 showed 36 to 51% identity to those of other members of the OAT family . Northern blot analysis revealed that hOAT3 mRNA is expressed in the kidney, brain, and skeletal muscle . When expressed in Xenopus laevis oocytes, hOAT3 mediated the transport of estrone sulfate (K(m) = 3.1 microM), p-aminohippurate (K(m) = 87.2 microM), methotrexate (K(m) = 10.9 microM), and cimetidine (K(m) = 57.4 microM) in a sodium-independent manner . hOAT3 also mediated the transport of dehydroepiandrosterone sulfate, ochratoxin A, PGE(2), estradiol glucuronide, taurocholate, glutarate, cAMP and uric acid . Estrone sulfate did not show any trans-stimulatory effects on either influx or efflux of {(3)H}estrone sulfate via hOAT3 . hOAT3 interacted with chemically heterogeneous anionic compounds, such as nonsteroidal anti-inflammatory drugs, diuretics, sulfobromophthalein, penicillin G, bile salts and tetraethyl ammonium bromide . The hOAT3 protein was shown to be localized in the basolateral membrane of renal proximal tubules and the hOAT3 gene was determined to be located on the human chromosome 11q12-q13.3 by fluorescent in situ hybridization analysis . These results suggest an important role of hOAT3 in the excretion/detoxification of endogenous and exogenous organic anions in the kidney.

Ned Tijdschr Geneeskd, 2001 Mar 31, 145(13), 612 - 3
{Penicillin for acute throat infections . Are there arguments for modifying the guidelines of the Dutch College of General Practitioners?}; van den Bosch WJ; A recent study concludes that a 7-day penicillin treatment for a sore throat is superior to a 3-day treatment or a placebo, because the symptoms are resolved two days earlier . Prior to this study, the difference--based on the conclusions of a Cochrane review--was thought to be just 8 hours . The total number of patients included was too small to conclude that penicillin could reduce the number of short-term and long-term complications . In the guidelines of the Dutch College of General Practitioners, a 7-day penicillin treatment for a sore throat is only recommended in severe cases . It is still quite acceptable for Dutch GPs to discuss the treatment options for a sore throat with their patients . A change to the current guidelines is not necessary.

Chemistry, 2001 Mar 2, 7(5), 959 - 71
An enzyme-labile safety catch linker for synthesis on a soluble polymeric support; Grether U et al.; The development of new and broadly applicable linker groups which are stable under a variety of reaction conditions and allow release of the desired products from the solid support under very mild conditions is of great interest in organic synthesis and combinatorial chemistry . We describe an enzyme-labile safety-catch linker which releases alcohols and amines through i) enzymatic cleavage of an amino group and ii) subsequent lactam formation . The linker group was investigated on different polymeric supports: TentaGel . PEGA, CPG-beads and the soluble polymer POE-6000 . From these linker-polymer conjugates 2-methoxy-5-nitrobenzyl alcohol was released by penicillin G acylase catalysed cleavage of a phenylacetamide and attack of the liberated benzylamine on the neighbouring ester group in ortho position . The model study revealed that only in the case of soluble POE-6000 conjugate high yields for the cleavage could be achieved . In the case of the other solid supports the enzyme does not have access to the interior of the polymer matrix . The application of the POE-6000 linker conjugate was investigated for various esters in Pd0-catalysed Heck-, Suzuki- and Sonogashira reactions as well as in a Mitsunobu reaction and cycloadditions . These studies proved that the linker is stable under a broad variety of reaction conditions and that the enzymatic method allows for release of the desired product alcohols under extremely mild conditions at pH 7 and 37 degrees C . In addition, the enzymatic reaction proceeds with complete chemoselectivity, that is other esters or amides are not attacked by the biocatalyst . In addition to alcohols amines can also be cleaved by means of the enzyme-initiated two-step process . In these cases the higher stability of amides as compared to esters requires warming to 60 degrees C to induce cyclization and release of the desired product.

Pediatr Infect Dis J, 2001 Mar, 20(3), 251 - 5
Isolation of Borrelia burgdorferi sensu lato from blood of children with solitary erythema migrans; Arnez M et al.; OBJECTIVES: To establish the frequency of isolation of Borrelia burgdorferi sensu lato from blood of children with solitary erythema migrans (EM) in Europe, to determine the strains of the isolated borreliae and to compare the clinical course and the outcome of the disease according to positive and negative blood culture result . METHODS: In the prospective study we included 134 consecutive patients younger than 15 years with solitary EM, referred to our institution in 1996 and 1997 . One milliliter of blood was withdrawn before treatment and cultured in modified Kelly-Pettenkofer medium . Isolated borreliae were typed according to LRFP analysis . Patients were treated with either penicillin V or cefuroxime axetil for 14 days . The posttreatment course was surveyed by follow-up visits during 1 year . RESULTS: B . burgdorferi sensu lato was isolated in 12 of 134 (9%) patients . Eleven blood isolates were typed: 10 were found to be B . afzelii and 1 was Borrelia garinii . Comparison of blood culture-positive and -negative patients revealed no differences in pretreatment characteristics or in posttreatment clinical course . However, worsening of local and/or systemic signs and symptoms at the beginning of antibiotic therapy (Jarish-Herxheimer's reaction) was identified more often in the blood culture-positive than in the blood culture-negative group (5 of 12 vs . 17 of 122, respectively; P = 0.0274) . CONCLUSIONS: The isolation rate of B . burgdorferi sensu lato from the blood of children with solitary EM was 9% . The majority of the isolates were B . afzelii . Blood culture-positive patients treated with oral antibiotics were not at greater risk for unfavorable course of the disease than patients with negative blood culture result.

J Chromatogr B Biomed Sci Appl, 2001 Mar 25, 753(1), 45 - 50
Efficient two-step chromatographic purification of penicillin acylase from clarified Escherichia coli ultrasonic homogenate; Sanchez J et al.; A two-step chromatographic purification procedure from clarified Escherichia coli ultrasonic homogenate was evaluated . The capture step included immobilized metal affinity chromatography with Cu2+ as metal ion . Two elution methods were performed: 1 M NH4Cl and 0.01 M imidazole . Respectively, we obtained a different purification fold (16.5 to 3.15) and a similar result for the recovery of activity (90-99%) . The best elution method was chosen for the procedure . The second step, hydrophobic interaction chromatography, gave a 3.8-fold purification with 77.7% of activity . The total procedure gave a 66-fold purification in relation to the initial crude extract with 70% for the recovery of activity and was performed without any conditioning step and at the same pH value.

Keio J Med, 2001 Mar, 50(1), 20 - 5
Molecular mechanisms of anesthesia; Ueda I; Anesthesia was a blessing to humankind . It is a miracle that simple molecules such as chloroform (CHCl3), diethyl ether (CH3.CH2.O.CH2.CH3), or nitrous oxide (N2O) induce a state of unconsciousness where patients can tolerate surgery . The diversity of the structures of these molecules indicates that there are no common receptors . The action of anesthetics is nonspecific and physical . After the demonstration by Meyer and Overton that anesthetic potencies correlate to their solubility into olive oil, the nonspecific lipid theories monopolized anesthesia theories for almost a century . The dominance of lipid theories invited repulsions against the nonspecificity idea . Protein theories that stress receptor bindings became the top mode . Nevertheless, the wide varieties of anesthetic molecules and the wide varieties of responding systems are difficult to reconcile with the specific interaction concept . This article discusses the recent progress and controversies on the molecular mechanisms of anesthesia . Anesthetics are unique drugs in pharmacology . They affect all macromolecules . The only comparable drugs are disinfectants . Both are nonspecific drugs . We use alcohols and phenols to wipe off the injection sites . We do not use penicillin or any other antibiotics for this purpose, because they are specific binders . Interestingly, these two nonspecific drugs opened the window for the modern medicine.

Acta Pol Pharm, 2000 Nov, 57 Suppl, 8 - 10
Screening and search for novel inhibitors of DD-peptidase 64-575; Rozbicka B et al.; The aim of the work was search for inhibitors of PBPs (penicillin binding proteins, DD-carboxypeptidase/transpeptidase, DD-peptidase) . Between 141 tested Streptomyces strains, 25% showed activity of inhibitors production . The inhibitors were produced by selected Streptomyces strains (NIH Culture Collection) . The culture supernatants of Streptomyces rimosus B PZH (inhibitor B) and Streptomyces rimosus NRRL 2234 (inhibitor 2234) exhibited the highest inhibition activity . Both inhibitors were purified by the use of: anion exchange chromatography and reversed phase chromatography (HPLC) . Inhibitor B is a gamma-lactam compound and inhibitor 2234 is a beta-lactam.

Ann Allergy Asthma Immunol, 2001 Mar, 86(3), 330 - 4
Severe serum sickness-like reaction to oral penicillin drugs: three case reports; Tatum AJ et al.; BACKGROUND: Because the use of heterologous sera has diminished, the incidence of serum sickness has declined . However, serum sickness-like reactions to nonprotein drugs continue to occur . METHODS: We report three cases of severe serum sickness-like reactions in adults to oral penicillin drugs . RESULTS: In each patient, significant symptom resolution occurred within 24 hours of starting therapy with oral corticosteroids . CONCLUSIONS: Serum sickness-like reactions to oral penicillin drugs may be more common than reported in the literature and can be very severe . No specific laboratory finding is universally present or definitively diagnostic . As with classic serum sickness, the diagnosis of serum sickness-like reaction is made clinically . In severe cases such as those presented here with debilitating joint symptoms or life-threatening angioedema, a diagnostic-therapeutic trial of prednisone, 40 to 60 mg at least once daily, is warranted.

Arch Microbiol, 2001 Feb, 175(2), 122 - 32
The Aspergillus nidulans homoaconitase gene lysF is negatively regulated by the multimeric CCAAT-binding complex AnCF and positively regulated by GATA sites; Weidner G et al.; In beta-lactam-antibiotic-producing fungi, such as Aspergillus (Emericella) nidulans, L-alpha-aminoadipic acid is the branching point of the lysine and penicillin biosynthesis pathways . To obtain a deeper insight into the regulation of lysine biosynthesis genes, the regulation of the A . nidulans lysF gene, which encodes homoaconitase, was studied . Band-shift assays indicated that the A . nidulans multimeric CCAAT-binding complex AnCF binds to two of four CCAAT motifs present in the lysF promoter region . AnCF consists at least of three different subunits, designated HapB, HapC, and HapE . In both a delta hapB and a delta hapC strain, the expression of a translational lysF-lacZ gene fusion integrated in single copy at the chromosomal argB gene locus was two to three-fold higher than in a wild-type strain . These data show that AnCF negatively regulates lysF expression . The results of Northern blot analysis and lysF-lacZ expression analysis did not indicate a lysine-dependent repression of lysF expression . Furthermore, mutational analysis of the lysF promoter region revealed that two GATA sites matching the GATA consensus sequence HGATAR positively affected lysF-lacZ expression . Results of Northern blot analysis also excluded that the global nitrogen regulator AreA is the responsible trans-acting GATA-binding factor.

Ophthal Plast Reconstr Surg, 2001 Mar, 17(2), 134 - 6
Rhinoorbitocerebral actinomycosis; Nithyanandam S et al.; PURPOSE: To report a case of actinomycotic orbital abscess with subdural empyema and pansinusitis, an unusual presentation of a rarely seen infection . METHODS: Case report . RESULTS: A 35-year-old man sought treatment for signs and symptoms of an orbital abscess 22 days after a dental extraction . Computed tomography demonstrated a left orbital abscess with left pansinusitis and a large subdural empyema . Surgical clearance of all purulent material was done followed by prolonged penicillin therapy . Culture of pus from all sources yielded Actinomycosis israelii . At the time of discharge and 1-month follow-up, the patient had 20/20 vision with no neurologic deficits . CONCLUSIONS: In orbital infections with atypical presentations, unusual pathogens should be considered as the causative agents.

J Biol Chem, 2001 May 25, 276(21), 18290 - 5 Epub 2001 Feb 21.
Alteration of the co-substrate selectivity of deacetoxycephalosporin C synthase . The role of arginine 258; Lee HJ et al.; Deacetoxycephalosporin C synthase is an iron(II) 2-oxoglutaratedependent oxygenase that catalyzes the oxidative ring-expansion of penicillin N to deacetoxycephalosporin C . The wild-type enzyme is only able to efficiently utilize 2-oxoglutarate and 2-oxoadipate as a 2-oxoacid co-substrate . Mutation of arginine 258, the side chain of which forms an electrostatic interaction with the 5-carboxylate of the 2-oxoglutarate co-substrate, to a glutamine residue reduced activity to about 5% of the wild-type enzyme with 2-oxoglutarate . However, other aliphatic 2-oxoacids, which were not co-substrates for the wild-type enzyme, were utilized by the R258Q mutant . These 2-oxoacids "rescued" catalytic activity to the level observed for the wild-type enzyme as judged by penicillin N and G conversion . These co-substrates underwent oxidative decarboxylation as observed for 2-oxoglutarate in the normal reaction with the wild-type enzyme . Crystal structures of the iron(II)- 2-oxo-3-methylbutanoate (1.5 A), and iron(II)-2-oxo-4-methylpentanoate (1.6 A) enzyme complexes were obtained, which reveal the molecular basis for this "chemical co-substrate rescue" and help to rationalize the co-substrate selectivity of 2-oxoglutaratedependent oxygenases.

J Chromatogr A, 2001 Feb 23, 910(1), 69 - 78
Determination of drug residues in water by the combination of liquid chromatography or capillary electrophoresis with electrospray mass spectrometry; Ahrer W et al.; Methods for the determination of drug residues in water have been developed based on the combination of liquid chromatography (LC) or capillary electrophoresis (CE) with mass spectrometry (MS) . For HPLC-MS two types of interfaces (pneumatically assisted electrospray ionization interface or an atmospheric pressure chemical ionization interface, respectively) were employed and compared in terms of detection limits . 2 mM Ammonium acetate at pH 5.5 and a methanol gradient was used for the HPLC-MS allowing the separation of a number of drugs such as paracetamol, clofibric acid, penicillin V, naproxen, bezafibrate, carbamazepine, diclofenac, ibuprofen and mefenamic acid . A 20 mM ammonium acetate solution, pH 5.1 was employed for the separation of clofibric acid, naproxen, bezafibrate, diclofenac, ibuprofen and mefenamic acid by CE-MS . Sample pretreatment was performed by solid-phase extraction (SPE) for HPLC-MS or by a combination of liquid-liquid extraction and SPE for CE-MS . The applicability of both the HPLC-MS and CE-MS method was demonstrated for several river water samples.

MMWR Morb Mortal Wkly Rep, 1999 Sep 10, 48(35), 777 - 9
Inadvertent use of Bicillin C-R for treatment of syphilis--Maryland, 1998; Anticonvulsion effect of acupuncture might be related to the decrease of neuronal and inducible nitric oxide synthases; Department of Neurobiology, Institute of Acupuncture Research, Shanghai Medical University, PR ChinaTo measure the levels of hippocampal nitric oxide synthase isoforms in penicillin induced epilepsy and to test the effect of electroacupuncture (EA) on changes of theses levels during epilepsy, we injected penicillin into rat hippocampus to make an epilepsy model and performed electroacupuncture treatment on "Feng Fu" (DU 16) and "Jin Suo" (DU 8) points in Wistar rats . Nitric Oxide synthase (NOS) mRNA levels of rat hippocampus were determined by reverse transcription-polymerase chain reaction (RT-PCR) . The neuronal nitric oxide synthase (nNOS) mRNA markedly increased (P<0.01) and inducible nitric oxide synthase (iNOS) mRNA significantly emerged during epilepsy, whereas no significant change in epithelial nitric oxide synthase (eNOS) mRNA was observed . EA inhibited the epilepsy and decreased nNOS (P<0.01) and iNOS (P<0.01) correspondingly but had no effect on the amount of eNOS mRNA . The data suggest that penicillin-induced epilepsy caused an increase in nNOS and iNOS, and the EA anticonvulsant effect might be related to the decrease of these nitric oxide synthases.

Clin Exp Allergy, 2001 Mar, 31(3), 438 - 43
Lack of allergic cross-reactivity to cephalosporins among patients allergic to penicillins; Novalbos A et al.; There are some contradicting data about clinical allergic cross-reactivity to cephalosporins among patients who have had a previous allergic reaction to penicillins . The purpose of this study was to assess the safety of administering cephalosporins to penicillin-allergic patients . The diagnosis of penicillin allergy was made by positive skin tests to penicillin reagents and/or provocation tests with the penicillin suspected of causing the allergic reaction . To assess the clinical tolerance to cephalosporins, 41 well-characterized penicillin allergic patients diagnosed by positive skin tests and/or provocation tests were challenged with three cephalosporins that do not share the same side chain to the penicillin that induced the reactions: cephazoline, cefuroxime and ceftriaxone . Skin prick and intradermal tests with all cephalosporins tested were negative . All penicillin-allergic patients tolerated therapeutic doses of the three cephalosporins tested (cephazoline, cefuroxime and ceftriaxone) without any ill effect . These results indicate that the risk of suffering from an allergic reaction on administering cephalosporins to penicillin-allergic patients seems to be very low, provided that cephalosporins with a different side chain to the penicillin responsible for the allergic reaction are used.

Klin Monatsbl Augenheilkd, 2001 Feb, 218(2), 116 - 20
{Vitamins C and E protect cultures of bovine lens epithelium from the damaging effects of blue light (430 nm) and UVA light (300-400 nm)}; Mayer UM et al.; BACKGROUND: In 1992 Radlmaier showed that catalase can protect bovine lens epithelial cultures from blue light . The following experiments have the aim to examine, if vitamin C and E have protective functions, also . MATERIAL AND METHODS: 367 cultures of bovine lens epithelial cells were incubated in Medium 199 added by 20% foetal calf serum FCS, by 125 I.U./ml penicillin, by 125 mg/ml Streptomycin, by 0.31 microgram/ml amphotericin B, by 2% L-Glutamin (200 mM), and by 1.25% Hepesbuffer . The incubation temperature was kept at 36 degrees C at a pCO2 of 5% . In order to avoid secondary morphologic alterations, we experimented only on the second to the third subculture . Light exposure followed three days after addition of the substances such as Cebion 500 (R) ad injection (6 mg/dl) and E-Vicotrat (R) ad injection (0.5 mg/dl) . The blue light (420-430 nm, Draeger) was applied in a baby bed at 36 degrees C for four hours (1.1 mW/cm) . The UV-A lamp was constructed and described by Heller {7}; at a wave length of 300-400 nm, the irradiation time was 10 minutes at 100 mW/cm2 . In morphologic evaluation we looked for criteria such as cell diameter, cellular wall alterations, cellular inclusions and vacuoles . The cell count was done after staining with the vital dye trypan-blue in Neubauer's chamber . In statistic evaluation we used the pair comparison of Tuckey and Kruskall-Wallis-Test . RESULTS: After addition of 0.5 mg/ml vitamin E: In 89 cultures, morphologic evaluation and cell count showed a significant protection against light toxicity: After Uv-A-irradiation we counted 50% more living cells and after blue light 30% more . After addition of 6 mg/ml Cebion vitamin C: Morphologic evaluation and cell count of 223 cultures showed them also to be significantly protected: after irradiation by UV-A we counted 25% more and after exposition to blue light 15% more living cells . CONCLUSION: The demonstrated experiments significantly showed, that vitamin C and vitamin E can protect lens epithelial cultures from toxic stress by blue and by UV-A light and might delay cataract formation in man.

Arch Med Res, 2000 Nov-Dec, 31(6), 608 - 12
Bisalbuminemia in two Croatian families; Dodig S et al.; BACKGROUND: Bisalbuminemia is a dysproteinemia characterized by the occurrence of two albumin fractions on serum protein separation by electrophoresis on cellulose acetate sheets . Bisalbuminemia may occur as a hereditary trait or as analytical interference with some drugs, especially penicillin . METHODS: Two patients with the finding of bisalbuminemia are presented . Both patients (patient 1 was a 4-1/2-month-old male infant, and patient 2 was a 15-year-old boy) were admitted for respiratory infection . RESULTS: Bisalbuminemia was detected by serum protein electrophoresis and confirmed by isoelectric focusing in pH gradient gel (pH range 4.0-6.5) . This finding was supported by simultaneous detection of abnormal albumin in the mother of patient 1, while the father had normal albumin . The abnormal fast albumin in both patients had an increased relative mobility of 1.08 when measured from the sample application position . CONCLUSIONS: The results presented are the first description of albumin mutations in Croatia (that according to the CISMEL group could be classified as ZC/HZ), and present the first step in identification prior to determination of structural change and amino acid sequence in the albumin molecule.

Arch Inst Pasteur Alger, 1998, 62, 32 - 9
{Blood determination of benzathine-penicillin used in acute joint rheumatism prophylaxis}; Merad B et al.; Our actual work studies the effectiveness in vivo of the Benzathin penicillin that is realized on 88 subjects suffering from a stable rheumatic fever . It has shown that: The first hours after an intramuscular injection, the benzathin penicillin is found at an efficient concentration superior to 0.02 ug/ml at the level of the blood . The highest dose in the blood is obtained the first 24 hours . The amount of antibiotic at the level of the blood is very efficient during 4 weeks.

Biochimie, 2001 Jan, 83(1), 99 - 102
Approaching the physiological functions of penicillin-binding proteins in Escherichia coli; Young KD; A rigid shell of peptidoglycan encases and shapes bacteria and is constructed and maintained by a diverse set of enzymes, among which are the penicillin-binding proteins (PBPs) . Although a great deal has been learned about how these proteins synthesize and modify peptidoglycan, the physiological functions of the multitude of bacterial PBPs remain enigmatic . We approached this problem by combining PBP mutations in a comprehensive manner and screening for effects on biochemical processes involving the passage of proteins or nucleic acids across the cell wall . The results indicate that the PBPs or their peptidoglycan product do have significant biological functions, including roles in determination of cell shape, in phage resistance, in induction of capsule synthesis, and in regulation of autolysis.

Cent Eur J Public Health, 2001 Feb, 9(1), 38 - 40
Sensitivity of Borrelia burgdorferi strains isolated in the Czech Republic; Janovska D et al.; We tested in vitro susceptibility of 5 strains of Borrelia burgdorferi sensu lato, isolated from patients in the Czech Republic, to penicillin G, ceftriaxone, cefotaxime, doxycycline and amoxycillin combined with clavulanic acid by broth macrodilution method on BSK medium . Results confirmed high efficacy of the tested drugs, particularly on B . afzelii and B . burgdorferi sensu stricto . A strain of B . garinii, isolated from cerebrospinal fluid, required a longer period of antibiotic activity before inhibitory effects were achieved . Penicillin G was effective only in higher concentrations, attainable by i . v . application . Ceftriaxone had the strongest borreliacidal activity.

Protein Eng, 2000 Dec, 13(12), 857 - 63
Characterization of the beta-lactam binding site of penicillin acylase of Escherichia coli by structural and site-directed mutagenesis studies; Alkema WB et al.; The binding of penicillin to penicillin acylase was studied by X-ray crystallography . The structure of the enzyme-substrate complex was determined after soaking crystals of an inactive betaN241A penicillin acylase mutant with penicillin G . Binding of the substrate induces a conformational change, in which the side chains of alphaF146 and alphaR145 move away from the active site, which allows the enzyme to accommodate penicillin G . In the resulting structure, the beta-lactam binding site is formed by the side chains of alphaF146 and betaF71, which have van der Waals interactions with the thiazolidine ring of penicillin G and the side chain of alphaR145 that is connected to the carboxylate group of the ligand by means of hydrogen bonding via two water molecules . The backbone oxygen of betaQ23 forms a hydrogen bond with the carbonyl oxygen of the phenylacetic acid moiety through a bridging water molecule . Kinetic studies revealed that the site-directed mutants alphaF146Y, alphaF146A and alphaF146L all show significant changes in their interaction with the beta-lactam substrates as compared with the wild type . The alphaF146Y mutant had the same affinity for 6-aminopenicillanic acid as the wild-type enzyme, but was not able to synthesize penicillin G from phenylacetamide and 6-aminopenicillanic acid . The alphaF146L and alphaF146A enzymes had a 3-5-fold decreased affinity for 6-aminopenicillanic acid, but synthesized penicillin G more efficiently than the wild type . The combined results of the structural and kinetic studies show the importance of alphaF146 in the beta-lactam binding site and provide leads for engineering mutants with improved synthetic properties.

Sex Transm Dis, 2001 Feb, 28(2), 92 - 8
Missed opportunities for congenital syphilis prevention in an urban southeastern hospital; Warner L et al.; BACKGROUND: Despite recent declines in syphilis rates nationally, recent outbreaks suggest that prevention of congenital syphilis remains an ongoing public health problem . GOALS: To identify missed opportunities for congenital syphilis prevention during prenatal care . STUDY DESIGN: Retrospective medical record review of 157 live birth or stillbirth deliveries that involved cases of congenital syphilis from Grady Memorial Hospital (Atlanta, GA) . RESULTS: The hospital congenital syphilis prevalence was 8.2 cases per 1,000 live births . Six percent of case patients were HIV positive . Opportunities for earlier maternal screening, treatment, or diagnosis were missed in 60% of case patients who received timely prenatal care . Congenital syphilis cases attributable to preventable missed opportunities were significantly more common among case patients with fewer prenatal visits (66% versus 28%, P = 0.01) . CONCLUSION: Provider efforts to reduce congenital syphilis in high-risk populations receiving prenatal care should focus on (1) screening patients at the first opportunity, at both the first prenatal visit and during the third trimester (i.e., 28 weeks); (2) performing on-site testing and same-day treatment; (3) providing appropriate treatment to infected women with penicillin allergy; (4) referring sex partners for treatment to prevent reinfection; and (5) screening all pregnant women attending emergency clinics.

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