Aliment Pharmacol Ther, 1996 Apr, 10(2), 181 - 5 Gastric mucosal infiltration by Helicobacter pylori favours bacterial survival after treatment; Neri M et al.; BACKGROUND: Although a number of patient and bacterial factors have been identified as predictors of treatment failure in Helicobacter pylori-associated gastritis, the causes of lack of response to treatment have not been fully elucidated . We hypothesized that bacterial infiltration of the gastric mucosa might be one of the factors responsible for treatment failure in patients harbouring the bacterium . METHODS: We studied 182 patients with gastritis who underwent anti-H . pylori treatment with different drugs . Gastric biopsies obtained at endoscopy, were examined for electron microscopic features of infiltration and damage . Patients were assigned to different treatment groups, and endoscopy, evaluation of H . pylori status and electron microscopy were repeated at least 4 weeks after the end of treatment . RESULTS: The overall H . pylori eradication rate was 65% . Eradication was achieved more frequently in patients without electron microscopic features of infiltration (85%), than in those patients with the bacteria deeply embedded into the gastric mucosa (45%; P < 0.0001) . No treatment appeared to be clearly superior for patients with the highest degree of mucosal infiltration . CONCLUSIONS: Bacterial mucosal infiltration may facilitate the survival of H . pylori during antibacterial treatment; moreover, electron microscopy may be helpful to identify patients potentially unresponsive to anti-H . pylori treatment. J R Soc Med, 1996 Apr, 89(4), 199 - 201 Splenectomy in a general hospital; Glass JM et al.; Splenectomy is often performed in patients with malignant disease or trauma who are at a high risk of complications . In the long term, it increases the risk of infection by encapsulated bacteria . An audit was performed to determine the reasons for splenectomy in a district general hospital, to review the results and complications of surgery, and to see how often the patients were prescribed antibacterial prophylaxis . Twenty-eight patients underwent splenectomy in 3 years . The indication was haematological disease in 13 and trauma in four . In the remaining nine the spleen was removed either as part of a radical gastrectomy or during some other abdominal procedure . Six of the 28 patients had died, one within 30 days from disseminated intravascular coagulopathy following an emergency gastrectomy and splenectomy for haematemesis, two from progressive haematological malignant disease, two from non-haematological malignancy, and one from bronchopneumonia . Of the nine patients (32%) with complications, three required a further laparotomy . Most patients had been prescribed pneumococcal vaccine (85%) and prophylactic antibiotics (93%). Arch Pharm (Weinheim), 1996 Apr, 329(4), 179 - 90 Syntheses and biological activities of new N1-aryl substituted quinolone antibacterials; Jurgens J et al.; A series of quinolones with a systematically varied substitution at the phenyl ring at N1 has been synthesized . Three lipophilicity descriptors (log K, log P, Rm) and the pKa values have been determined as well as the microbiological activity: The MIC values for eight different strains of three Gram-positive and three Gram-negative species and the inhibitory concentrations of DNA supercoiling (IC90 and IC100) were determined . From a principal component and a QSAR analysis relationships between antibacterial activity concerning the whole-cell system and electronic properties as well as the length of the substituents at the phenyl rings could be derived . The activity in a cell-free system was governed by the lipophilicity and the width of the substituents . It is speculated that the quinolones take a defined place in the DNA gyrase-DNA complex which is characterized by polar amino acids . This is in agreement with findings from studies of mutant gyrases. J Antibiot (Tokyo), 1996 Apr, 49(4), 390 - 4 Chemistry of pseudomonic acid . Part 16.Aryl and heteroaryl ketone derivatives of monic acid; Abson A et al.; The synthesis, antibacterial activities, murine pharmacokinetic and infection model data for a range of aryl and heteroaryl ketone derivatives of monic acid (2a) are reported . The best results were found for the 3-furyl and 2-methoxy thiazol-5-yl analogues. Eur J Biochem, 1996 Apr 1, 237(1), 303 - 10 A class of highly potent antibacterial peptides derived from pardaxin, a pore-forming peptide isolated from Moses sole fish Pardachirus marmoratus; Oren Z et al.; Pardaxin, a 33-amino-acid pore-forming polypeptide toxin isolated from the Red Sea Moses sole Pardachirus marmoratus, has a helix-hinge-helix structure . This is a common structural motif found both in antibacterial peptides that can act selectively on bacterial membranes (e.g., cecropin), and in cytotoxic peptides that can lyse both mammalian and bacterial cells (e.g., melittin) . Herein we show that pardaxin possesses a high antibacterial activity with a significantly reduced hemolytic activity towards human red blood cells (hRBC), compared with melittin . Its potency is comparable to that of other known native antibacterial peptides such as magainin, cecropins and dermaseptins . To determine the structural features responsible for the selective hemolytic and antibacterial activities, and the structural requirements for a high antibacterial activity, 8 truncated and modified pardaxin analogues were synthesized and structurally and functionally characterized . Each peptide was synthesized with a free carboxylate or amino group (i.e., aminated form) at its C-terminus . The aminated form of pardaxin has both high hemolytic and antibacterial activity . A truncated analogue, with 11 amino acids removed from the C-terminal domain, had dramatically reduced hemolytic activity . However, the aminated form of this analogue was significantly more potent that pardaxin against most bacteria tested, suggesting that the C-terminal tail of pardaxin is responsible for non-selective activity against erythrocytes and bacteria . Furthermore, a positive charge added to its N-terminus significantly increased its antibacterial activity and abolished its low hemolytic activity . The 22-amino-acid C-terminal domain and the short 11-amino-acid N-terminal domain were, in their aminated forms, active only against gram-positive bacteria . Secondary-structure determination using circular dichroism spectroscopy revealed that all the aminated analogues had 25-80% more alpha-helical content in 40% CF3CH2OH/water than their non-aminated forms . Using model phospholipid membranes it was found that all the analogues that were less hemolytic but had retained antibacterial activity could permeate acidicly charged phospholipid vesicles better than zwitterionic phospholipid vesicles, a property characteristics of all the native antibacterial peptides tested so far (e.g., cecropins, magainins and dermaseptins) . Pardaxin and its analogues therefore represent a new class of antibacterial peptides that can serve as a basis for the design of therapeutic agents . Furthermore, negative-staining electron microscopy revealed that total inhibition of bacterial growth was due to total lysis of the bacterial wall . Therefore, it might be more difficult for bacteria to develop resistance to such a destructive mechanism, compared with the more specific mechanisms of the currently used antibiotics. Nucleic Acids Res, 1996 Apr 1, 24(7), 1238 - 45 Drosophila immunity: a comparative analysis of the Rel proteins dorsal and Dif in the induction of the genes encoding diptericin and cecropin; Gross I et al.; In Drosophila, bacterial challenge induces the rapid transcription of several genes encoding potent antibacterial peptides . The upstream sequences of the diptericin and cecropin Al genes, which have been investigated in detail, contain two, respectively one sequence element homologous to the binding site of the mammalian nuclear factor kappaB . These elements have been shown to be mandatory for immune-induced transcription of both genes . Functional studies have shown that these kappaB-related elements can be the target for the Drosophila Rel proteins dorsal and Dif . Here we present a comparative analysis of the transactivating capacities of these proteins on reporter genes fused to either the diptericin or the cecropin kappaB-related motifs . We conclude from our results: (i) the kappaB motifs of the diptericin and cecropin genes are not functionally equivalent; (ii) the dorsal and Dif proteins have distinct DNA-binding characteristics; (iii) dorsal and Dif can heterodimerize in vitro; (iv) mutants containing no copies of dorsal and a single copy of Dif retain their full capacity to express the diptericin and cecropin genes in response to challenge. J Biol Chem, 1996 Mar 29, 271(13), 7609 - 14 Slow binding inhibition of phospho-N-acetylmuramyl-pentapeptide-translocase (Escherichia coli) by mureidomycin A; Brandish PE et al.; Enzymes of the membrane cycle of reactions in bacterial peptidoglycan biosynthesis remain as unexploited potential targets for antibacterial agents . The first of these enzymes, phospho-N-acetylmuramyl-pentapeptide-translocase (EC 2.7.8.13), has been overexpresed in Escherichia coli and solubilized from particulate fractions . The work of W.A . Weppner and F.C . Neuhaus ((1977) J . Biol . Chem . 252, 2296-303) has been extended to establish a usable routine fluorescence-based continuous assay for solubilized preparations . This assay has been used in the characterization of the natural product, mureidomycin A as a potent slow binding inhibitor of the enzyme with Ki and Ki* of 36 nM and 2 nM, respectively. J Biol Chem, 1996 Mar 29, 271(13), 7305 - 8 Diastereoisomers of cytolysins, a novel class of potent antibacterial peptides; Shai Y et al.; An amphipathic alpha-helical structure is considered to be a prerequisite for the lytic activity of most short linear cytolytic polypeptides that act on both mammalian cells and bacteria . This structure allows them also to exert diverse pathological and pharmacological effects, presumably by mimicking protein components that are involved in membrane-related events . In this study D-amino acid-incorporated analogues (diastereomers) of the cytolysin pardaxin, which is active against mammalian cells and bacteria, were synthesized and structurally and functionally characterized . We demonstrate that the diastereomers do not retain the alpha-helical structure, which in turn abolishes their cytotoxic effects on mammalian cells . However, they retain a high antibacterial activity, which is expressed in a complete lysis of the bacteria, as revealed by negative staining electron microscopy . The disruption of the alpha-helical structure should prevent the diastereomer analogues from permeating the bacterial wall by forming transmembrane pores but rather by dissolving the membrane as a detergent . These findings open the way for a new strategy in developing a novel class of highly potent antibacterial polypeptides for the treatment of infectious diseases, due to the increasing resistance of bacteria to the available antibacterial drugs. Biochem Biophys Res Commun, 1996 Mar 27, 220(3), 502 - 8 Purification and characterization of lysozyme from hemolymph of Heliothis virescens larvae; Lockey TD et al.; Lysozyme is an important antibacterial protein in the insect defense system . Lysozyme was isolated from hemolymph of Heliothis virescens larvae using gel filtration and ion-exchange chromatography . Heliothis lysozyme had a molecular mass of 16,000 daltons by SDS-PAGE . Using acid gel electrophoresis, Heliothis lysozyme migrated faster than egg white lysozyme . The pI of Heliothis lysozyme was estimated as greater than 9.5 . Heliothis lysozyme had specific bactericidal activity against three Gram-positive bacteria but no activity against Escherichia coli . The bactericidal activity was stable at 100 degrees C at pH 3.0 after 60 min incubation, but was labile at 100 degrees C at pH 6.8 after 60 min incubation . Heliothis lysozyme was an inducible protein that increased 9 times when comparing unvaccinated with vaccinated larvae . Lysozyme from H . virescens was more similar in molecular mass, heat sensitivity and pH sensitivity to lysozyme isolated from Galleria mellonella and Bombyx mori than to lysozyme isolated from Hyalophora cecropia. Biochim Biophys Acta, 1996 Mar 13, 1279(2), 125 - 9 Transport of the antibacterial agent (6S)-6-fluoroshikimate and other shikimate analogues by the shikimate transport system of Escherichia coli; Jude DA et al.; We show that the antibacterial agent, (6S)-6-fluoroshikimate, is a substrate for the shikimate transport system of Escherichia coli because in exchange-diffusion experiments it displaced intracellular {14C}shikimate with the same kinetics as did unlabelled shikimate . Other shikimate analogues were also substrates: as judged by similar experiments or, in the case of (6R)-6-fluoroshikimate, by inference. Arch Intern Med, 1996 Mar 11, 156(5), 513 - 20 An analysis of bacteremias during dental extractions . A double-blind, placebo-controlled study of chlorhexidine; Lockhart PB; BACKGROUND: The literature is unclear concerning the nature and incidence of bacteremias from oral surgical procedures, the relationship of these bacteremias to dental disease, and the preventive benefit of antibacterial mouth rinses . OBJECTIVE: To determine the incidence and nature of bacteremias during single-tooth extractions in adults . METHODS: A double-blind, randomized placebo-controlled study of 70 patients in which the status of dental disease was compared with the incidence and nature of aerobic and anaerobic bacteremias following a single-tooth extraction and the antibacterial effect of rinses with chlorhexidine hydrochloride . Multiple indicators of dental disease were evaluated and recorded before the surgical procedure . Timing of the mouth rinses, the steps in the surgical procedure, and the two blood drawings were controlled for . RESULTS: Thirty-one (94%) of 34 control patients and 62 (89%) of 70 patients overall had blood cultures positive for organisms at either the 1-minute and or 3-minute mark following the initiation of surgery . The majority of cultures yielded gram-positive cocci . Cultures yielded polymicrobial organisms in 17 patients (24%) . Although there was a wide range of severity of odontogenic disease, this did not correlate with results of blood cultures . However, there was a statistically significant difference in the incidence of blood cultures positive for organisms at both shorter (<3 minutes, P=.04) and longer (>6 minutes, P=.04) surgery times . There was not statistically significant difference in either the incidence of blood cultures positive for organisms or in the nature of organisms identified between the chlorhexidine and placebo groups . CONCLUSIONS: Single-tooth extraction should be expected to cause a bacteremia regardless of the status of the dentition or periodontium . Mouth rinses with chlorhexidine not significantly alter the number of positive blood cultures or the nature of the organisms at either of the two blood drawings. Proc Natl Acad Sci U S A, 1996 Mar 5, 93(5), 1747 - 52 The catalytic mechanism of beta-lactamases: NMR titration of an active-site lysine residue of the TEM-1 enzyme; Damblon C et al.; Beta-Lactamases are widespread in the bacterial world, where they are responsible for resistance to penicillins, cephalosporins, and related compounds, currently the most widely used antibacterial agents . Detailed structural and mechanistic understanding of these enzymes can be expected to guide the design of new antibacterial compounds resistant to their action . A number of high-resolution structures are available for class A beta-lactamases, whose catalytic mechanism involves the acylation of a serine residue at the active site . The identity of the general base which participates in the activation of this serine residue during catalysis has been the subject of controversy, both a lysine residue and a glutamic acid residue having been proposed as candidates for this role . We have used the pH dependence of chemical modification of epsilon-amino groups by 2,4,6,-trinitrobenzenesulfonate and the pH dependence of the epsilon-methylene 1H and 13C chemical shifts (in enzyme selectively labeled with {epsilon-13C}lysine) to estimate the pKa of the relevant lysine residue, lysine-73, of TEM-1 beta-lactamase . Both methods show that the pKa of this residue is > 10, making it very unlikely that this residue could act as a proton acceptor in catalysis . An alternative mechanism in which this role is performed by glutamate-166 through an intervening water molecule is described. Presse Med, 1996 Mar 2-9, 25(8), 337 - 41 {New antibacterial vaccinal strategies}; Kok M et al.; The prevalence of bacterial diseases and bacterial resistance is currently increasing, emphasizing the need for alternative vaccines . The body of knowledge on molecular determinants of bacterial virulence has tremendously increased during the recent years, and new molecular targets are available for immunization . Intramuscular injection of plasmid DNA containing bacterial genes with a suitable appropriate promotor is followed by transfection of host cells which will produce bacterial proteins, and elicit humoral and cytotoxic lymphocyte-mediated responses . Mucosal vaccines induce local immune response, both by type 1 and type 2 dependent pathways . Living bacterial vectors can provide conditional delivery of foreign antigens in selected host sites . A series of new substances allows us to steer the immune response in a way that optimizes immune protection . All this impressive progress will undoubtedly lead to the development of novel vaccines enabling us to ensure improved protection against bacterial diseases. Int Endod J, 1996 Mar, 29(2), 125 - 30 In-vitro antibacterial susceptibility of bacteria taken from infected root dentine to a mixture of ciprofloxacin, metronidazole and minocycline; Hoshino E et al.; The aim of this study was to clarify the antibacterial effect of a mixture of ciprofloxacin, metronidazole and minocycline, with and without the addition of rifampicin, on bacteria taken from infected dentine of root canal walls . The efficacy was also determined against bacteria of carious dentine and infected pulps which may the precursory bacteria of infected root dentine . This efficacy was estimated in vitro by measuring bacterial recovery on BHI-blood agar plates in the presence or absence of the drug combination . Bacteria ranging in number from 10(2) to 10(6) occurred in samples of infected root dentine (27 cases) . However, none was recovered from the samples in the presence of the drug combination at concentrations of 25 micrograms ml-1 each . The respective drug alone (10, 25, 50 and 75 micrograms ml-1) substantially decreased the bacterial recovery, but could not kill all the bacteria . Bacteria taken from carious dentine (25 cases) and infected pulps (12 cases) were also sensitive to the drug combination . These results may indicate that the bactericidal efficacy of the drug combination is sufficiently potent to eradicate bacteria from the infected dentine of root canals. Int Endod J, 1996 Mar, 29(2), 118 - 24 Sterilization of infected root-canal dentine by topical application of a mixture of ciprofloxacin, metronidazole and minocycline in situ; Sato I et al.; The aim of this study was to observe the potential of a mixture of ciprofloxacin, metronidazole and minocycline to kill bacteria in the deep layers of root canal dentine in situ . After the crowns of extracted teeth had been removed, the drug combination (0.5 mg of each drug), or sterile saline, as the control, was placed in the root canals which had been previously irrigated ultrasonically with G4M EDTA . The penetration and bactericidal efficacy were estimated by various procedures as follows . (1) A cell suspension of E . coli was placed into small cavities prepared parallel to the root canals on the cut planes of nine single-rooted teeth . The teeth were then entirely covered with blue inlay wax . At time 0, and at 5h, 24h and 48h after the drug combination had been applied, cells of E . coli were recovered from the cavities by washing the cavities several times with sterile saline solution, and were cultured on the surfaces of heart-infusion (HI) agar plates . Total colony-forming units were tuen counted . Bacterial recoveries decreased with time, and no bacteria were recovered 48 h after application of the drug combination, while bacteria survived in all cases with the controls, (2) After the drug combination or sterile saline had been placed into and sealed in the root canal with blue inlay wax, the teeth were placed into HI agar plates where cells of E . coli had been inoculated . After culturing, a clear zone caused by the inhibition of bacterial growth was observed around the teeth, but not in the control experiment . (3) After sampling infected root dentine of 12 freshly extracted teeth as positive controls, the drug combination (0.5 mg each) was placed in the root canals . No bacteria were recovered from the infected dentine of the root canal wall 24 h after application of the drug combination, except in one case in which a few bacteria were recovered . On the basis of these results, penetration through dentine and antibacterial efficacy of the drug combination can be expected against bacteria infecting the dentine of the root canal wall in situ when the drugs were placed in root canals which had been irrigated ultrasonically. Arch Pharm (Weinheim), 1996 Mar, 329(3), 115 - 9 From chloroquine to antineoplastic drugs? the story of antibacterial quinolones; Radl S; Chemotherapy has not only proved valuable in treating many diseases but the history of discovery of some drugs makes exciting reading . The aim of this article is to outline one such story. Antibiot Khimioter, 1996 Mar, 41(3), 3 - 8 {Rubomycin Q1--an anthracycline metabolite from Streptomyces coeruleorubidus 2679, a strain producing rubomycin C}; Fedorova GB et al.; In the programme of screening of biologically active secondary metabolites produced by Streptomyces coeruleorubidus 2679 a new reddish-violet component (rubomycin Q1) with antibacterial and cytotoxic activity was isolated from the culture fluid of the organism . Some physico-chemical and biological properties of a chromatographically pure rubomycin Q1 were investigated . It was shown with the use of 1H NMR, UV, IR and mass spectrometry that rubomycin Q1 was an anthracycline antibiotic (9,10-anhydro-13-desoxycarminomycin). Antibiot Khimioter, 1996 Mar, 41(3), 20 - 4 {Conjugative transfer and expression of R plasmids of the genus Pseudomonas in the cells of Pseudomonas mallei C-5}; Filonov AE et al.; Conjugative transfer of the incompatibility group plasmids Inc P-2, Inc P-3, Inc P-4 and Inc P-5 as well as the plasmids of Pseudomonas sp . of an unknown incompatibility group to the cells of Pseudomonas mallei C-5 was shown possible for the first time . The inheritance of the transferred plasmids and the expression of the markers of resistance to antibacterial drugs were stable . Clones with reserved virulence, lowered virulence and no virulence were detected among the transconjugants . The results of the immunization by the avirulent cells of P . mallei C-5 (RP4) were evident of low immunogenic capacity of the microbe. J AOAC Int, 1996 Mar-Apr, 79(2), 375 - 9 Determination of tetracyclines in animal feeds in the presence of other drugs by thin-layer chromatography and microbiological method; Markakis PK; This method was developed to separate, detect, and quantitate oxytetracycline (OTC) or chlortetracycline hydrochloride (CTC.HCl) in animal feeds in the presence of 11 other drugs: 3 nitrofurans, 2 macrolide antibiotics, 3 sulfonamides, 2 coccidiostatics, and 1 antibacterial growth promoter . OTC or CTC.HCl was separated from coexisting drugs and detected by thin-layer chromatography, then quantitated microbiologically by the agar diffusion method . Analysis of 125 experimental animal feed samples fortified at 5 levels (7.5-400 ppm) with OTC or CTC.HCl and at 1 level (50 ppm) with the rest of the drugs, respectively, gave a limit of quantitation of 1.25 or 0.625 ppm, a recovery of 90.6 or 92.9%, and a coefficient of variation of 2.9-6.1 or 2.3-4.4%. Pharmazie, 1996 Mar, 51(3), 148 - 51 Synthesis and reactions of some new 4H-pyrano{3,2-c}benzopyran-5-one derivatives and their potential biological activities; Shaker RM; Several new 4H-pyrano{3,2-c}benzopyran-5-ones (6a-g and 10) which exhibited antibacterial and fungicidal activity, have been synthesized via a one flask multicomponent condensation of aldehydes with malononitrile and 4-hydroxycoumarin . The reactions of 6a with several nucleophilic reagents are reported. Drugs, 1996 Mar, 51(3), 460 - 82 Pantoprazole . A review of its pharmacological properties and therapeutic use in acid-related disorders; Fitton A et al.; Pantoprazole is an irreversible proton pump inhibitor which, at the therapeutic dose of 40mg, effectively reduces gastric acid secretion . In controlled clinical trials, pantoprazole (40mg once daily) has proved superior to ranitidine (300mg once daily or 150mg twice daily) and equivalent to omeprazole (20mg once daily) in the short term (< or = 8 weeks) treatment of acute peptic ulcer and reflux oesophagitis . Gastric and duodenal ulcer healing proceeded significantly faster with pantoprazole than with ranitidine, and at similar rates with pantoprazole and omeprazole . The time course of gastric ulcer pain relief was similar with pantoprazole, ranitidine and omeprazole, whereas duodenal ulcer pain was alleviated more rapidly with pantoprazole than ranitidine . Pantoprazole (40mg once daily) showed superior efficacy to famotidine (40mg once daily) in ulcer healing and pain relief after 2 weeks in patients with duodenal ulcer in a large multicentre nonblinded study . In mild to moderate acute reflux oesophagitis, significantly greater healing was obtained with pantoprazole than with ranitidine and famotidine, whereas similar healing rates were seen with pantoprazole and omeprazole . Pantoprazole showed a significant advantage over ranitidine in relieving symptoms of heartburn and acid regurgitation . Reflux symptoms were similarly alleviated by pantoprazole and omeprazole . Preliminary results indicate that triple therapy with pantoprazole, clarithromycin and either metronidazole or tinidazole is effective in the treatment of Helicobacter pylori-associated disease; however, these findings require confirmation in large well-controlled studies . Pantoprazole appears to be well tolerated during short term oral administration, with diarrhoea (1.5%), headache (1.3%), dizziness (0.7%), pruritus (0.5%) and skin rash (0.4%) representing the most frequent adverse events . The drug has lower affinity than omeprazole or lansoprazole for hepatic cytochrome P450 and shows no clinically relevant pharmacokinetic or pharmacodynamic interactions at therapeutic doses with a wide range of drug substrates for this isoenzyme system . In conclusion, pantoprazole is superior to ranitidine and as effective as omeprazole in the short term treatment of peptic ulcer and reflux oesophagitis, has shown efficacy when combined with antibacterial agents in H . pylori eradication, is apparently well tolerated and offers the potential advantage of minimal risk of drug interaction. Antimicrob Agents Chemother, 1996 Mar, 40(3), 780 - 3 Penetration of cefetamet pivoxil and cefuroxime axetil into the maxillary sinus mucosa at steady state; Stoeckel K et al.; The penetration of cefetamet and cefuroxime into the maxillary sinus mucosa after the administration of cefetamet pivoxil and cefuroxime axetil was investigated in patients undergoing elective surgery of the maxillary sinus . A total of 27 patients, 13 for cefetamet pivoxil and 14 for cefuroxime axetil, ranging from 15 to 70 years of age participated in this study . Each patient received three oral doses of either one tablet of cefetamet pivoxil (500 mg of GLOBOCEF) or two film tablets of cefuroxime axetil (125 and 250 mg of ZINAT) every 12 h . Sinus mucosa tissue samples were removed during surgery at times ranging from 2 to 4.5 h after the last oral administration . Blood samples were collected before drug administration, 2 h after the first and third doses, and concomitantly with tissue sample collection during surgery . All samples were analyzed by high-performance liquid chromatography . The concentrations of cefetamet and cefuroxime in plasma samples measured concomitantly with those in tissue samples ranged between 0.83 and 4.5 micrograms/ml for cefetamet and 0.59 and 3 micrograms/ml for cefuroxime . The mean tissue-to-plasma ratios calculated with reference to total (bound plus unbound) plasma drug concentrations were 0.60 (range, 0.52 to 0.77) for cefetamet (n = 4) and 0.38 (range, 0.28 to 0.44) for cefuroxime (n = 6) . Both drugs seem to penetrate freely and easily into the sinus mucosa . The antibacterial activities of cefetamet pivoxil and cefuroxime axetil in cases of sinusitis therefore depend mainly on their achieved active plasma drug concentrations and their intrinsic activities in inhibiting the causative organism(s). Antimicrob Agents Chemother, 1996 Mar, 40(3), 734 - 8 Predictors of effect of ampicillin-sulbactam against TEM-1 beta-lactamase-producing Escherichia coli in an in vitro dynamic model: enzyme activity versus MIC; Firsov AA et al.; The clinical outcome in patients treated with ampicillin-sulbactam may not always be predictable by disc susceptibility testing or with the MIC as determined with a constant level (4 micrograms/ml) of the beta-lactamase inhibitor (MIC1) . The enzyme activities (EA) and the MICs estimated at a constant ratio of ampicillin to sulbactam of 2:1 (MIC2) for 15 TEM-1 beta-lactamase-producing strains of Escherichia coli were examined as alternatives to MIC1 as predictors of the antibacterial effects of this combined drug as studied in an in vitro model which simulates ampicillin-sulbactam pharmacokinetic profiles observed in human peripheral tissues . Integral parameters describing the area under the bacterial count-time curve (AUBC), the area between the normal growth curve, and the killing curve of bacteria exposed to antibiotic (ABBC), and the second parameter expressed as a percentage of its maximal hypothetical value (ABBC/ABBCmax) were calculated . All three parameters correlated well with EA (AUBC, r = 0.93; ABBC, r = -0.88; ABBC/ABBCmax, r = -0.91) and with MIC2 (r = 0.94, -0.94, and -0.95, respectively) but not with MIC1 . Both EA and MIC2 can be considered reliable predictors of the antibacterial effect of ampicillin-sulbactam in an in vitro model . These correlations suggest that in vitro kinetic-dynamic models might be useful to reexamine established susceptibility breakpoints obtained with data based on the MIC1 (MICs obtained with constant levels of beta-lactamase inhibitors) . These data also suggest that quantitative determinations of bacterial beta-lactamase production and MICs based on the component concentration ratio observed in vivo might be useful predictors of the effect of ampicillin-sulbactam and other beta-lactam-inhibitor combinations. Antimicrob Agents Chemother, 1996 Mar, 40(3), 652 - 8 Transport of the antibacterial agent oxazolidin-2-one and derivatives across intestinal (Caco-2) and renal (MDCK) epithelial cell lines; Ranaldi G et al.; The transepithelial passage of the orally bioavailable antibacterial agent oxazolidin-2-one (OXa) and 10 derivatives has been studied with human intestinal (Caco-2) and canine renal (MDCK) cell lines grown on polycarbonate filters . The transepithelial passage was assayed in the apical-to-basolateral (AP-to-BL) direction and in the opposite direction (BL to AP) in both cell lines . The observed passage rates of OXa were similar in both directions in the two cell lines, suggesting passive diffusion . This was further confirmed by the fact that transport kinetics were linear as a function of initial concentration . The rates of AP-to-BL passage of OXa and seven of the derivatives in both cell lines were linearly related to lipophilicity, whether expressed as high-passage liquid chromatography retention time or as the logarithm of the n-octanol-water partition coefficient (log P) . These data suggest that the lipophilicity of OXa is important for its observed bioavailability after oral administration . Interestingly, three of the derivatives exhibited a higher passage rate than predicted by lipophilicity . Further studies indicated that this transport was saturable, similar in the two directions, and not affected by energy depletion, suggesting the presence of an additional carrier-mediated facilitated-transport mechanism. Antimicrob Agents Chemother, 1996 Mar, 40(3), 621 - 6 In vitro antibacterial activity of omeprazole and its selectivity for Helicobacter spp . are dependent on incubation conditions; Sjostrom JE et al.; Factors affecting the in vitro antibacterial activity of omeprazole were studied . Our data show that 3H-labeled omeprazole covalently bound to Helicobacter pylori and to other gram-negative and gram-positive bacteria . The compound was found to bind to a broad range of proteins in H . pylori, and at pH 5, binding was enhanced 15-fold compared with binding at pH 7 . The bactericidal activity correlated to the degree of binding, and at pH 5, a pH at which omeprazole readily converts to the active sulfenamide form, beta-mercaptoethanol, a known scavenger of sulfenamide, and fetal calf serum, to which noncovalent protein binding of omeprazole is known to occur, reduced the level of binding and almost entirely abolished the bactericidal activity . At pH 7 the killing activities of omeprazole and structural analogs (e.g., proton pump inhibitors) were dependent on the time-dependent conversion (half-life) to the corresponding sulfenamide . The bactericidal activity exerted by the sulfenamide form at pH 5 was not specific for the genus Helicobacter . However, in brucella broth at pH 7 with 10% fetal calf serum, only Helicobacter spp . were susceptible to omeprazole, with MBCs in the range of 32 to 64 micrograms/ml, and MBCs for more stable proton pump inhibitors were higher . Wild-type H . pylori and its isogenic urease-deficient mutant were equally susceptible to omeprazole . Thus, the urease is not a lethal target for omeprazole action in H . pylori . In conclusion, the antibacterial activities of omeprazole and analogs are dependent on pH and the composition of the medium used . Thus, at a low pH in buffer, these compounds have a nonselective action, whereas in broth at neutral pH, the mechanism of action is selective for Helicobacter spp. Antimicrob Agents Chemother, 1996 Mar, 40(3), 581 - 5 The macrolide-lincosamide-streptogramin B resistance phenotypes characterized by using a specifically deleted, antibiotic-sensitive strain of Streptomyces lividans; Pernodet JL et al.; Genes conferring resistance to macrolide, lincosamide, and streptogramin B (MLS) antibiotics via ribosomal modification are widespread in bacteria, including clinical isolates and MLS-producing actinomycetes . Such erm-type genes encode enzymes that mono- or dimethylate residue A-2058 of 23S rRNA . The different phenotypes resulting from monomethylation (MLS-I phenotype, conferred by erm type I genes) or dimethylation (MLS-II phenotype due to erm type II genes) have been characterized by introducing tlrD or ermE, respectively, into an MLS-sensitive derivative of Streptomyces lividans TK21 . This strain (designated OS456) was generated by specific replacement of the endogenous resistance genes lrm and mgt . The MLS-I phenotype is characterized by high-level resistance to lincomycin with only marginal resistance to macrolides such as chalcomycin or tylosin, whereas the MLS-II phenotype involves high-level resistance to all MLS drugs . Mono- and dimethylated ribosomes were introduced into a cell-free protein-synthesizing system prepared from S . lividans and compared with unmodified particles in their response to antibiotics . There was no simple correlation between the relative potencies of MLS drugs at the level of the target site (i.e., the ribosome) and their antibacterial activities expressed as MICs. J Indian Med Assoc, 1996 Mar, 94(3), 91 - 5 Dual use of silver for management of chronic bone infections and infected non-unions; Nand S et al.; Broad spectrum antibacterial effect of electrically generated silver ions has been fully established . Present work consists of clinical evaluation of beneficial antibacterial effect of silver ions liberated electrically with the help of locally manufactured power pack in 920 proved cases of chronic osteomyelitis with or without pathological fractures and septic non-unions . Wound debridement, silver iontophoresis, proper immobilisation and subsequent wound care yielded not only control of bone infections in 85% cases, but also produced healing of pathological fractures in 83% patients . Results remained unaffected by age or sex of patient, type of bone involved, duration of previous illness or type of previous treatment . Follow-up varied from 6 months to 10 years . This technique is likely to open a new chapter in treatment of chronic resistant bone infections and septic non-unions due to open fractures particularly in developing countries of the world. J Pharmacol Exp Ther, 1996 Mar, 276(3), 1143 - 8 Transport of levofloxacin in a kidney epithelial cell line, LLC-PK1: interaction with organic cation transporters in apical and basolateral membranes; Ohtomo T et al.; The interactions of levofloxacin, a pyridonecarboxylic acid antibacterial drug, with the organic cation transport systems expressed in a pig kidney epithelial cell line, LLC-PK1, were examined . The transcellular transport of tetraethylammonium was remarkably inhibited by levofloxacin, accompanied by a marked increase in the cellular accumulation of tetraethylammonium in the LLC-PK1, monolayers grown on collagen-coated membrane filters . The results obtained by efflux and uptake of tetraethylammonium revealed that levofloxacin drastically inhibited the apical transport activity rather than the basolateral uptake of tetraethylammonium . Under conditions in which the apical efflux of tetraethylammonium was blocked by pretreatment with p-chloromercuribenzene sulfonate, levofloxacin showed a moderate inhibitory effect against the basolateral uptake of tetraethylammonium . Transepithelial flux of levofloxacin from the basolateral side to the apical side was much greater than the flux in the opposite direction . The flux of levofloxacin was influenced by the apical side pH, resulting in a decreased cellular accumulation by lowering pH . The basal-to-apical transport and cellular accumulation of levofloxacin were not inhibited by either tetraethylammonium or cimetidine . These results suggested that levofloxacin interacts with the apical H+/organic cation antiport system to a greater extent than with the basolateral system . However, transcellular transport of levofloxacin would be mediated by the transport systems which are distinct from the systems for tetraethylammonium in LLC-PK1 cells. Infection, 1996 Mar-Apr, 24(2), 151 - 5 The effects of ciprofloxacin on human chondrocytes in cell culture; Mont MA et al.; Ciprofloxacin is a highly potent antibacterial agent that is used extensively in bone and joint infections . Because of reports of potential chondro-toxicity in animals, the effects of this drug on cells derived from human cartilage were tested in liquid micromass and agarose gel cultures . An inhibition of cell proliferation as indicated by a decrease in {3H}-thymidine uptake and bromodeoxyuridine labeling at ciprofloxacin concentrations of 0.5 and 50 mg/l was found which corresponded to the therapeutic and toxic serum levels . There was no effect on proteoglycan synthesis as indicated by 35SO4 incorporation . Immunocytochemistry showed no changes in morphology or staining patterns for type-I procollagen, type-II collagen, keratan sulfate and unsulfated chondroitin . Because the amount of inhibition of DNA synthesis varied with different ciprofloxacin concentrations, this data suggests that this agent has a differential effect on newly differentiating cells and might be the basis for contraindication in pediatric patients. Antiviral Res, 1996 Mar, 29(2-3), 163 - 73 Inhibition of human immunodeficiency virus type 1 infectivity by a new amine bellenamine; Ikeda R et al.; Bellenamine, (R)-3,6-diamino-N-(aminomethyl)hexanamide (molecular weight 174), produced by Streptomyces nashvillensis, which has been reported to have weak antibacterial activity and to slightly enhance the immune response, showed potent activity against human immunodeficiency virus type 1 (HIV-1) . Its mode of action was investigated . Bellenamine inhibited de novo infection of human T cells with HIV-1, at a 50% effective concentration (EC50) of 0.62 micrograms/ml (3.6 microM) . Its 50% cytotoxic concentration (CC50) was over 2000 micrograms/ml (11.5 mM) and thus its cytotoxicity was quite low . When HIV-1-infected cells were treated with bellenamine or glycosylation inhibitors, they produced virus with reduced infectivity, and thus bellenamine inhibited the secondary spread of HIV-1 in vitro similarly to glycosylation inhibitors . However, bellenamine did not change the apparent molecular weights of env or gag proteins, unlike glycosylation inhibitors . Bellenamine showed no significant activity against virus adsorption, reverse transcriptase, viral protease or the glycosylation process . The antiviral mechanism of bellenamine remains to be examined further. J Pharm Biomed Anal, 1996 Mar, 14(5), 561 - 9 Spectrophotometric and spectrofluorimetric estimation of ciprofloxacin and norfloxacin by ternary complex formation with eosin and palladium(II); el Walily AF et al.; Spectrophotometric and spectrofluorimetric methods for the determination of two broad-spectrum fluoroquinolone antibacterials (ciprofloxacin and norfloxacin), either in pure form or in tablets, are described . Both methods are based on the formation of a ternary complex between palladium(II), eosin and the fluoroquinolone in the presence of methyl cellulose, as surfactant . Spectrophotometrically, under the optimum conditions, the ternary complexes showed an absorption maximum at 545 nm, with apparent molar absorptivities of 3.4 x 10(4) and 2.7 x 10(4) 1 mol-1 cm-1 and Sandell's sensitivities of 1.01 x 10(-2) and 1.12 x 10(-2) micrograms cm-2 for ciprofloxacin and norfloxacin, respectively . The solution of the ternary complex obeyed Beer's law in the concentration range 3-10 micrograms ml-1 for both quinolones . The proposed method was applied to the determination of the two drugs in pharmaceutical tablets . A fluorescence quenching method for the determination of both quinolones by forming this ternary complex was also investigated for the purpose of enhancing the sensitivity of the determination . The results obtained by the application of both procedures and the USP XXIII methods were in good agreement and statistical comparison by means of Student's t-test and the variance ratio F-test showed no significant differences between the three methods. Vestn Otorinolaringol, 1996 Mar-Apr, (2), 42 - 5 {Use of rovamycin and amox-clav in patients with infectious-inflammatory pathology of the ORL organs}; Kriukov AI et al.; Clinical and microbiological findings led the authors to the conclusion that antibacterial drugs rovamycin and amox-clav are active against ENT infection and inflammation . The trial included 69 and 42 patients given rovamycin and amox-clav, respectively. Farmaco, 1996 Mar, 51(3), 189 - 96 Synthesis and antibacterial activity of C-4 thio- and dithiocarbamate monobactam derivatives; Cascio G et al.; New series of monobactam antibiotics, bearing thio-and dithiocarbamate derivatives as C-4 side chain, were synthesized . Some compounds were found to have good antibacterial activity against Gram-negative bacteria. Burns, 1996 Mar, 22(2), 113 - 6 Morphology of glycerol-preserved human cadaver skin; Richters CD et al.; Donor allograft skin preserved in 85 per cent glycerol has been used successfully as a temporary coverage for large burn wounds . The glycerol preservation is a method with low costs and has practical advantages such as antibacterial and virucidal effects . This report shows that the glycerol treatment did not affect the fundamental structural integrity of the skin . Intact keratinocytes and Langerhans cells with their characteristic Birbeck granules were still present in the glycerol-treated skin . After treatment with glycerol, the cells in the prepared epidermal cell suspensions were non-viable . MHC class II positive and CD1a positive cells could still be identified in situ and in the suspension. Neurology, 1996 Mar, 46(3), 824 - 6 Recovery from coma caused by primary CNS mantle cell lymphoma presenting as encephalitis; Finsterer J et al.; We report a 74-year-old woman with progressive cognitial deterioration and changes in personality . She had no clinical signs of an inflammatory CNS process, but brain CT and MRI scans and cytologic examination of the CSF were initially indicative of encephalitis and ventriculitis . Antiviral and antibacterial therapy had no effect on the course of symptoms, and patient became comatose . We established the diagnosis of a primary CNS mantle cell lymphoma (PCNSL) and began corticosteroids . Within a few days the patient became alert and was able to walk again . Nonenhancing and non-space-occupying PCNSLs are rare but must be considered in the differential diagnosis of coma and encephalitis . Comatose PCNSL patients without radiographic evidence for herniation can be successfully treated with corticosteroids even if the EEG has a burst suppression pattern. Toxicology, 1996 Feb 22, 107(2), 99 - 109 Toxic effects of some conifer resin acids and tea tree oil on human epithelial and fibroblast cells; Soderberg TA et al.; The present study was undertaken to assess and compare the in vitro cytotoxic effects of three resin acid analogues: dehydrobietic acid, podocarpic acid, O-methylpodocarpic acid; an essential oil from Australia (tea tree oil); and tapped oleoresin from Thailand, on human epithelial and fibroblast cells, using a quantitative neutral red spectrophotometric assay . All of the investigated compounds except for tea tree oil exhibited a cytotoxic activity which was proportional to their concentrations and time of exposure up to 24 h, i.e . higher concentrations and longer time of exposure caused increased cell death . Dehydroabietic acid and the oleoresin were the most toxic compounds followed by O-methylpodocarpic acid, whereas podocarpic acid and tea tree oil showed a lower level of toxicity . On the basis on these findings it is concluded that an isopropyl group on the aromatic C-ring is of great importance for the cytotoxicity of the tested abietane resin acids, thus indicating that the cytotoxic activity of oleoresins most probably is caused by synergistic or additive effects of resin acids . The results from this work support the view that antibacterial activity parallels cytotoxic activity which suggests a similar mode of action, most probably exerted by membrane-associated reactions. FEBS Lett, 1996 Feb 19, 380(3), 237 - 40 Broad spectrum antibiotic activity of the skin-PYY; Vouldoukis I et al.; Neuropeptide Y (NPY) and polypeptide YY (PYY) are two ubiquitous neuropeptides, found in brain and intestines, respectively, where they exert important regulatory functions . In this study, a new member of the YY family recently isolated from amphibian skin, skin-PYY (SPYY), is reported to inhibit irreversibly the proliferation of a broad spectrum of pathogenic microorganisms . NPY and PYY are shown to be endowed with the same activity . Their potency is similar to that of other antibacterial peptides which have been shown to exert their function by disintegrating the bacterial membrane . These findings and the fact that the C-terminal alpha-helical domain SPYY14-36, which is highly conserved among family members, was responsible for killing microorganisms and for permeation of phospholipid vesicles, suggested that the antibiotic activity may emerge via a membrane permeation mechanism . These findings also raise the question whether NPY and PYY exert in vivo a similar function in mammals. Eur J Biochem, 1996 Feb 15, 236(1), 263 - 71 Formation of pores in Escherichia coli cell membranes by a cecropin isolated from hemolymph of Heliothis virescens larvae; Lockey TD et al.; The insect humoral defense system produces antibacterial peptides called cecropins . Cecropins were initially isolated from Hyalophora cecropia pupae and have since been isolated and identified in various insects . In this study, we have isolated and identified a cecropin from Heliothis virescens larvae . Rabbit IgG were raised against synthetic cecropin B . Affinity chromatography with the rabbit anti-(cecropin B) IgG was used to isolate a cecropin from hemolymph of H . virescens larvae . Acid gel electrophoresis followed by a bacterial-overlay analysis showed that Heliothis cecropin is a basic peptide of low molecular mass with bactericidal activity against Escherichia coli K12 D31 . Heliothis cecropin is therefore analogous to synthetic cecropin B . One unresolved issue concerning cecropins and other antibiotic peptides is the mode of action by which they kill bacteria . By means of electron microscopy and immunocytochemistry with gold-labeled rabbit anti-cecropin IgG, binding of purified and synthetic cecropin to the cell membranes of E . coli K12 D31 cells was observed . Small lesions in the cell membrane were seen that had a diameter of 9.6 nm and internal pore of 4.2 nm . The Heliothis cecropin was found to be a pore-forming molecule that causes lesions in the cell membrane of E . coli K12 D31 . The lesions lead to leakage of cytoplasmic contents and death of bacteria. Eur J Biochem, 1996 Feb 15, 236(1), 200 - 6 Covalent association of lipopolysaccharide at the hemocyte surface of insects is an initial step for its internalization--Protein-tyrosine phosphorylation requirement; Charalambidis ND et al.; It is well known that lipopolysaccharide (LPS) of Gram-negative bacteria triggers antibacterial responses to mammalian macrophages {Weinstein, S., Gold, M . R . & DeFranco, A . (1991) Proc . Natl Acad . Sci . USA 88, 4148-4152} and insect hemocytes {Charalambidis, N.D., Zervas, C.G., Lambropoulou, M., Katsoris, P.G . & Marmaras, V.J . (1995) Eur J . Cell Biol . 67, 32-41}, via protein-tyrosine phosphorylation . In this study we show that insect hemocytes in response to LPS facilitate internalization of LPS (either cell-associated or cell-free) . According to our data, the recognition and covalent association of LPS (either cell-associated or cell-free) to the hemocyte surface are essential initial steps for LPS internalization . LPS (Escherichia coli) recognizes membrane effector 47-kDa protein (p47) and then crosslinks to membrane-associated p47 (mp47) via the intermediacy of tyrosine derivatives generated by the action of phenol oxidase, as is the case for cuticular protein-chitin crosslinks during sclerotization {Shaefer, J., Kramer, K.J., Garbow, J.R., Jacob, G.S., Stejskal, E.O., Hopkins, T.L . & Speirs, R.D . (1987) Science 235, 1200-1204} . The covalent association of LPS to the hemocyte surface appears to be a prerequisite for LPS internalization as judged by the resistance of LPS binding to dissociation by proteinase K . In addition, our results show that the effector molecules participating in LPS covalent association at the cell surface and LPS internalization are not involved in LPS-induced activation of hemocytes . However, the fact that genistein, as well as the inhibitors of LPS-dependent secretion, block LPS covalent association at the cell surface and LPS internalization provides a preliminary characterization of an LPS signal-transduction-dependent process which is apparently involved. J Biol Chem, 1996 Feb 9, 271(6), 3052 - 7 Active site-directed inactivation of Escherichia coli glucosamine-6-phosphate synthase . Determination of the fructose 6-phosphate binding constant using a carbohydrate-based inactivator; Bearne SL; Glucosamine-6-phosphate synthase (GlmS) catalyzes the formation of glucosamine 6-phosphate from fructose 6-phosphate using glutamine as the ammonia source . Because N-acetylglucosamine is an essential building block of both bacterial cell walls and fungal cell wall chitin, the enzyme is a potential target for antibacterial and antifungal agents . N-Iodoacetylglucosamine 6-phosphate is an active site-directed irreversible inactivator of GlmS from Escherichia coli (kinact/KI = 17 (+/-3) m-1 s-1) . Both fructose 6-phosphate and glutamine protect the enzyme from inactivation, indicating that this reagent is directed at both the sugar binding site and the glutamine binding site . Protection studies with fructose 6-phosphate demonstrate that the value of the dissociation constant for fructose 6-phosphate is 3.3 (+/-0.5) x 10(-7) m, approximately 3 orders of magnitude less than the Kia value for this substrate determined from initial velocity experiments (Badet, B., Vermoote, P., and Le Goffic, F . (1988) Biochemistry 27, 2282-2287). J Toxicol Environ Health, 1996 Feb 9, 47(2), 115 - 23 Effects of new quinolone antibacterial agents on mammalian chromosomes; Shimada H et al.; The clastogenic effects of several new quinolones (ciprofloxacin, enoxacin, levofloxacin, nalidixic acid, ofloxacin, pipemidic acid, and N1-cyclopropyl quinolones for drug candidate) were studied cytogenetically using Chinese hamster lung cells (CHL) and the mouse micronucleus test . Some N1-cyclopropyl quinolones strongly induced chromosomal aberration on CHL cells, and some, but not all, were also capable of inducing micronuclei in mouse bone marrow cells . Levofloxacin showed weak clastogenicity in CHL cells but did not induce either micronuclei in mouse bone marrow or unscheduled DNA synthesis (UDS) in rat hepatocytes when administered to intact live animals . The lack of concordance between in vitro and in vivo assays could reflect the differences in the tissue levels of the drugs and the in vitro conditions. FEBS Lett, 1996 Feb 5, 379(3), 273 - 8 Antibacterial activity of secretolytin, a chromogranin B-derived peptide (614-626), is correlated with peptide structure; Strub JM et al.; Amongst the chromogranin B (CGB) derived fragments naturally generated in bovine chromaffin granules and detected in the extracellular space, we recently identified a major peptide corresponding to the 614-626 sequence of CGB . This peptide, named secretolytin, shared an interesting sequence homology with the lytic domain of cecropins and displayed a potent antibacterial activity . The aim of the present study was to determine the structural features of secretolytin necessary for this biological activity . Our results suggest that an alpha-helical amphipathic structure common to secretolytin, cecropins and pig myeloid antibacterial peptide may account for the antibacterial activity. J Med Chem, 1996 Feb 2, 39(3), 729 - 35 Structure-activity relationships of the quinolone antibacterials against mycobacteria: effect of structural changes at N-1 and C-7; Renau TE et al.; The re-emergence of tuberculosis infections which are resistant to conventional drug therapy has demonstrated the need for alternative chemotherapy against Mycobacterium tuberculosis . As part of a study to optimize the quinolone antibacterials against M . tuberculosis, we have prepared a series of N-1- and C-7-substituted quinolones to examine specific structure-activity relationships between modifications of the quinolone at these two positions and activity against mycobacteria . The compounds, synthesized by literature procedures, were evaluated for activity against Mycobacterium fortuitum and Mycobacterium smegmatis as well as Gram-negative and Gram-positive bacteria . The activity of the compounds against M . fortuitum was used as a barometer of M . tuberculosis activity . The results demonstrate that (i) the activity against mycobacteria was related more to antibacterial activity than to changes in the lipophilicity of the compounds, (ii) the antimycobacterial activity imparted by the N-1 substituent was in the order tert-butyl > or = cyclopropyl > 2,4-difluorophenyl > ethyl approximately cyclobutyl > isopropyl, and (iii) substitution with either piperazine or pyrrolidine heterocycles at C-7 afforded similar activity against mycobacteria. J Med Chem, 1996 Feb 2, 39(3), 680 - 5 Identification of a novel oxazolidinone (U-100480) with potent antimycobacterial activity; Barbachyn MR et al.; During the course of our investigations in the oxazolidinone antibacterial agent area, we have identified a subclass with especially potent in vitro activity against mycobacteria . The salient structural feature of these oxazolidinone analogues, 6 (U-100480), 7 (U-101603), and 8 (U-101244), is their appended thiomorpholine moiety . The rational design, synthesis, and evaluation of the in vitro antimycobacterial activity of these analogues is described . Potent activity against a screening strain of Mycobacterium tuberculosis was demonstrated by 6 and 7 (minimum inhibitory concentrations or MIC's < or = 0.125 micrograms/mL) . Oxazolidinones 6 and 8 exhibit MIC90 values of 0.50 micrograms/mL or less against a panel of organisms consisting of five drug-sensitive and five multidrug-resistant strains of M . tuberculosis, with 6 being the most active congener . Potent in vitro activity against other mycobacterial species was also demonstrated by 6 . For example, 6 exhibited excellent in vitro activity against multiple clinical isolates of Mycobacterium avium complex (MIC's = 0.5-4 micrograms/mL) . Orally administered 6 displays in vivo efficacy against M . tuberculosis and M . avium similar to that of clinical comparators isoniazid and azithromycin, respectively . Consideration of these factors, along with a favorable pharmaco-kinetic and chronic toxicity profile in rats, suggests that 6 (U-100480) is a promising antimycobacterial agent. Antibiot Khimioter, 1996 Feb, 41(2), 35 - 9 {Increased effectiveness of etiotropic therapy of experimental plague in albino mice at the stage of generalized infection}; Ryzhkova VV et al.; Therapeutic efficacies of various drugs were studied comparatively in the treatment of experimental plague in albino mice at the stage of the infection generalization . It was shown that out of the tested drugs such as ciprofloxacin, amikacin, gentamicin, rifampicin and polymyxin B only ciprofloxacin provided a rather high therapeutic effect in the treatment of the plaque septic form . The in vitro and in vivo experiments demonstrated that ciprofloxacin had an antitoxic action on lipopolysaccharide (LPS) and the plague microbe toxin . In comparison to ciprofloxacin, polymyxin B had a higher neutralizing activity . It was found that the efficacy of the experimental plague treatment at the stage of the infection generalization increased with the use of combinations of the drugs with antitoxic and antibacterial activities (ciprofloxacin and polymyxin B). J Chemother, 1996 Feb, 8(1), 52 - 4 Activity of amoxicillin, metronidazole, bismuth salicylate and six aminoglycosides against Helicobacter pylori; Brenciaglia MI et al.; The in vitro activity of metronidazole, amoxicillin, bismuth salicylate and some aminoglycosides, such as ribostamycin, gentamicin, amikacin, tobramycin, streptomycin and netilmicin was evaluated against 60 clinical isolates of Helicobacter pylori using the agar dilution technique . All 60 strains were susceptible to amoxicillin, with minimum concentrations able to inhibit 50% (MIC 50) and 90% (MIC 90) of strains equal to 0.031 microgram/ml and 0.25 microgram/ml, respectively . Of the aminoglycosides, ribostamycin, streptomycin and amikacin had a little lower activity (MIC 50 of 2 micrograms/ml, MIC 90 of 4-8 micrograms/ml) than gentamicin, tobramycin and netilmicin, with MIC 50s of 0.125 microgram/ml and MIC 90s of 0.25 microgram/ml . Metronidazole was effective against the majority of the strains, but we found ten resistant strains . Finally, bismuth salicylate showed only slight antibacterial activity. Antimicrob Agents Chemother, 1996 Feb, 40(2), 387 - 92 Molecular epidemiology of fluoroquinolone-resistant Escherichia coli bloodstream isolates from patients admitted to European cancer centers; Oethinger M et al.; Previous reports have suggested an increasing incidence of highly fluoroquinolone-resistant Escherichia coli causing bacteremia among cancer patients on prophylactic therapy . We used genotyping by pulsed-field gel electrophoresis of chromosomal DNA digests and random amplified polymorphic DNA fingerprinting to study clonal relationships among such isolates obtained at 10 cancer centers located across Europe and the Middle East . Analysis by both methods indicated that isolates from different centers were genotypically unrelated to each other . There were five centers from which more than one individual patient isolate was available, and most demonstrated significant within-center genetic diversity of strains . Strains shared among patients could be identified at two centers . At the center with the largest number of bloodstream isolates from cancer patients available, fluoroquinolone-resistant control isolates from surgical patients and fluoroquinolone-susceptible control isolates from patients admitted to medical services during the same time period were unrelated to resistant cancer patient isolates and to each other as well . A substantial number of fluoroquinolone-resistant isolates (19 of 58) were nontypeable by pulsed-field gel electrophoresis . Fluoroquinolone resistance was commonly associated with multiple antibiotic resistance to chemically unrelated antibacterial agents irrespective of the origin of the isolates. Antimicrob Agents Chemother, 1996 Feb, 40(2), 302 - 6 Susceptibility of Helicobacter pylori to bactericidal properties of medium-chain monoglycerides and free fatty acids; Petschow BW et al.; Previous studies have shown that various short- and medium-chain free fatty acids (FFAs) and their corresponding monoacylglycerol esters (MGs) have antibacterial activity in vitro against primarily gram-positive bacteria . More recent studies have also shown that the growth of Helicobacter spp . is inhibited by linoleic acid and arachidonic acid . The purpose of the present study was to evaluate the susceptibility of Helicobacter pylori to the in vitro bactericidal properties of medium-chain MGs and FFAs . Incubation of H . pylori with saturated MGs, ranging in carbon chain length from C10:0 to C14:0, at 1 mM caused a 4-log-unit or greater reduction in the number of viable bacteria after exposure for 1 h . Lower levels of bactericidal activity were observed with C9:0, C15:0, and C16:0 MGs . In contrast, lauric acid (C12:0) was the only medium-chain saturated FFA with bactericidal activity against H . pylori . The MGs and FFAs were bactericidal after incubation for as little as 15 min at neutral or acidic pHs . Higher levels of MGs and FFAs were required for bactericidal activity in the presence of higher amounts of protein in liquid diets . We also found that the frequency of spontaneous development of resistance by H . pylori was higher for metronidazole and tetracycline (10(-5) to 10(-6)) than for C10:0 MG, C12:0 MG, and C12:0 FFA (< 10(-8)) . Collectively, our data demonstrate that H . pylori is rapidly inactivated by medium-chain MGs and lauric acid and exhibits a relatively low frequency of spontaneous development of resistance to the bactericidal activity of MGs . Further studies are needed to establish whether MGs may be useful either alone or with other known therapeutic agents in the management of H . pylori infections in humans. Phytochemistry, 1996 Feb, 41(2), 571 - 3 A rearranged abietane diterpenoid from Plectranthus hereroensis; Batista O et al.; A new abietane diterpenoid has been isolated from the aerial parts of Plectranthus hereroensis, together with two known diterpenes . The structure of the new substance, 3 beta-acetoxy-6 beta,7 alpha,12-trihydroxy-17(15-->16);18(4-->3)-bisabeo-abieta-4(1 9),8,12,16-tetraene- 11,14-dione, was established by spectroscopic means and by comparison with closely related compounds . This diterpene showed moderate antibacterial activity. Eur J Epidemiol, 1996 Feb, 12(1), 33 - 5 Hyalohyphomycosis caused by Paecilomyces variotii in an obstetrical patient; Athar MA et al.; A case of hyalohyphomycosis, caused by Paecilomyces variotii, has been described in a 31-year-old female, who had undergone a cesarean section in her 39th week of pregnancy for a trial of labour . Five days following delivery, she complained of sharp, cramp-like pains, localized to the incisional site . She became febrile (38.2 degrees C) . An ultrasound examination revealed a complex mass and fluid within the pelvis and upper abdomen . The fluid was drained by a needle aspiration and the patient was administered a regimen of antibacterial drugs . Microscopic examination did not reveal any bacteria in a gram stained preparation and cultures were negative as well . However, the fluid demonstrated a few segments of septate, hyaline hyphae, with cultures yielding a pure growth of P . variotii . An exoantigen procedure, currently under development, was helpful in confirming the identity of the patient's fungus . The patient's condition improved following needle aspiration and her recovery was uneventful . It is reiterated that certain infections, attributed to low-grade opportunistic pathogens, such as P . variotii, may be cured by proper surgical drainage. East Afr Med J, 1996 Feb, 73(2), 115 - 9 Prescription writing in Gondar outpatient teaching hospital, Ethiopia; Desta Z et al.; A total of 19,119 prescriptions consecutively written between January-July 1992 were collected from Gondar outpatient hospital selling pharmacy and reviewed to determine physician's adherence to the basic principles of prescription order writing . In 36.6%, 16.8% and 12.4% of the prescriptions, respectively, age, sex and chart numbers of patients were not recorded . Twelve percent, 7%, 6.4%, 5.8% and 1.6% of the prescriptions did not indicate routes of drug administration, directions for drug use, frequency of drug administration, drug dose and duration of treatment, respectively . No prescription order had special advice or warnings to the patient and in 10.8% of the cases date was omitted . Out of the dispensed drugs, 82.9% were written in generic names and over 70% were included in the Essential Drug List of Ethiopia . The five most commonly dispensed individual drugs were ampicillin (10.4%), paracetamol (9.5%), TB 450 + isoniazid (7.4%), penicillin G (6.8%) and aspirin (5.8%) . As therapeutic classes, antiinfectives were most common (47.8%) of which antibacterials constituted 38.1%, followed by analgesic-antipyretics (17.5%) . Most drugs were prescribed by young medical interns and dispensed by less qualified personnel . Our preliminary survey indicates that essential components of a prescription order were omitted to a great extent and suggested to modify the existing undergraduate pharmacotherapeutic teaching in order to promote rational use and prescribing before bad habits get a chance to develop . The type of drugs dispensed at the selling pharmacy could not be beneficial to the patient without competent professional patient counselling, delivery of correct information as well as appropriate prescription monitoring. Fundam Appl Toxicol, 1996 Feb, 29(2), 280 - 6 Effect of bile duct ligation and unilateral nephrectomy on brain concentration and convulsant potential of the quinolone antibacterial agent levofloxacin in rats; Akahane K et al.; To mimic the excretion route of the quinolone antibacterial agent levofloxacin (LVFX) in humans, we produced an excretion-limited (EL) model in male Sprague-Dawley rats by bile duct ligation and unilateral nephrectomy . We then examined the relationship between brain levels of LVFX and its convulsant effects in control and EL animals . Serum concentrations of LVFX in EL animals (EL + LVFX) were 2.38- and 1.59-fold and brain concentrations were 1.33- and 1.19-fold those of the controls (control + LVFX) at 30 min after a single intravenous injection of 10 and 100 mg/kg LVFX, respectively . Furthermore EL animals became more susceptible to the convulsant effect of LVFX with a 1.28-fold decrease in convulsion-inducing dose . In combination with oral pretreatment with 400 mg/kg 4-biphenylacetic acid (BPAA), convulsion-inducing doses in the control (control + LVFX + BPAA) and EL (EL + LVFX + BPAA) groups were markedly decreased by 2.25 and 9 times that of the control + LVFX group . EL operation and BPAA pretreatment slowed the elimination of LVFX in the serum and brain 4 hr later in the following order: EL + LVFX + BPAA, control + LVFX + BPAA, EL + LVFX, and control + LVFX groups . This order reflects that for the convulsion-inducing doses . These results suggest that EL rats may be a useful model for humans and that the convulsant effect of LVFX with or without BPAA arises not only from the attainment of maximum brain concentration but also from delayed disappearance from the brain. J Chemother, 1996 Feb, 8 Suppl 2, 31 - 6 Antibacterial in vitro activity of fourth generation cephalosporins; Hancock RE et al.; Cefpirome, cefepime and cefaclidine are distinguished by having a positively charged quaternary ammonium at carbon 3 of the dihydrothiazone ring . This confers the distinctive advantages of higher permeability across the outer membrane and low affinity for chromosomal cephalosporinases compared to the third generation cephalosporins which lack this quaternary ammonium moiety . These properties result in a marked advantage against resistant mutants of several species containing either derepressed class C chromosomal beta-lactamases or variant class A beta-lactamase . These unique properties have led to the suggestion that these compounds represent a "fourth generation" of cephalosporins. J Chemother, 1996 Feb, 8 Suppl 2, 7 - 22 The chemistry and structure-activity relationships of C3-quaternary ammonium cephem antibiotics; Laws A et al.; The observation of a broad spectrum of antibacterial activity for cefpirome and for cefepime highlighted the benefits of combining a C3-quaternary ammonium substituent with the (Z)-2-(2-aminothiazole-4-yl)-2-methoxyiminoacetamido side chain at C7 . The quaternary nitrogen imparts beta-lactamase stability and improves both the cell penetration and the pharmacokinetic properties of these antibiotics . A variety of different quaternary ammonium substituents have been added, successive alterations in the groups attached to nitrogen have extended the activity of the fourth generation compounds . A number of different methods for attaching the quaternary ammonium group have been established, including the direct linkage to the C3-methylene, linkage via a C3-thiomethylene and also linkage via an alkenyl bridge . A number of different strategies have been developed for the preparation of these derivatives and these have been collated in this review . The beta-lactamase stability of fourth generation cephalosporins can be attributed to the formation of a transiently stable modified acyl-enzyme . The extent to which the modified acyl-enzyme contributes to the beta-lactamase stability is very much dependent on the leaving ability (nucleofugacity) of the C3-substituent . The influence of the quaternary ammonium substituents, on the formation of the modified acyl-enzyme, will be discussed. Curr Opin Immunol, 1996 Feb, 8(1), 14 - 9 Immunity to eukaryotic parasites in vector insects; Richman A et al.; Mosquitoes and blackflies have been the focus of recent efforts to elucidate factors influencing the susceptibility of vector insects to metazoan and protozoan parasites of medical significance . Vector species exhibit variation in cellular and humoral immune responses, as highlighted by studies of melanotic encapsulation and components of the phenoloxidase system . Significant progress has been made in the development of genetic maps based upon molecular markers, leading to the genetic analysis of loci influencing susceptibility . The identification of specific inducible antibacterial peptides, and the cloning of genes encoding immune effector proteins as well as potential regulatory factors, open the path to fruitful studies of vector insect innate immunity and its relationship to insect-parasite interactions. Planta Med, 1996 Feb, 62(1), 65 - 6 An antibacterial thiophene from Balsamorhiza sagittata; Matsuura H et al.; Balsamorhiza sagittata, a species of ethnopharmacological interest in British Columbia, is reported to have antibacterial and antifungal properties . An antibacterial compound isolated from this species was identified as 7,10-epithio-7,9-tridecadiene-3,5,11-triyne-1,2-diol based on the HMQC and HMBC experiments. Planta Med, 1996 Feb, 62(1), 22 - 7 In vitro biological activities of alkaloids from Cryptolepis sanguinolenta; Cimanga K et al.; In our biological screening of higher plants, an aqueous and an 80% EtOH extract from the root bark of Cryptolepis sanguinolenta showed potent antibacterial, anticomplementary, and moderate antiviral activities, but no antifungal effect could be detected . Bioassay-guided fractionation of the 80% EtOH extract led to the isolation of three alkaloids: quindoline (1), hydroxycryptolepine (2), cryptolepine.HCl (3), and the corresponding base cryptolepine (4) . All compounds strongly inhibited the growth of Gram-positive bacteria (MIC < or = 100 micrograms/ml) and showed a moderate (MIC = 125 or 250 micrograms/ml), a weak (MIC = 500 micrograms/ml), or no activity (MIC > 500 micrograms/ml) against selected Gram-negative bacteria . They also possessed a bactericidal effect depending on the bacterial strain . Compounds 1, 2 and 3 displayed a dose-dependent inhibitory effect on the classical pathway of the complement system while compounds 2 and 3 activated the alternative pathway, except for compound 1 . Compound 3 was found to possess an antiherpetic activity . Compounds 1 and 4 showed no antiviral effect, but were quite cytotoxic in the antiviral test system down to a concentration of 1 microgram/ml. J Antimicrob Chemother, 1996 Feb, 37(2), 315 - 22 Retention of antibacterial activity and bacterial colonization of antiseptic-bonded central venous catheters; Bach A et al.; We determined how long antiseptic impregnation with silver sulphadiazine and chlorhexidine (SCC) on polyurethane central venous double- or triple-lumen catheters is retained in vivo . A total of 116 antiseptic catheters were tested for antibacterial activity in an in-vitro bioassay after various periods of iv catheterization . Segments from the subcutaneous (sc) and intravenous (iv) portions of the catheters were cultured . The results of test antiseptic catheters were compared with those from 117 noncoated control (c) catheters . Retention of antibacterial activity followed an exponential curve and lasted for up to 520 h after catheter insertion . Significant differences (P = 0.0001) between SSC and C catheters were noticed with regard to the quantitative level of bacterial colonization (SSC-sc 87 +/- 34 vs C-sc 584 +/- 122; SSC-iv 52 +/- 17 vs C-iv 286 +/- 57; all values are given as mean cfu +/- S.E.M.), and the frequency of bacterial colonization (SSC-sc 20.7% vs C-sc 38.5%, P = 0.0047; SSC-iv 18.1% vs C-iv 30.8%, P = 0.0361) . There was no significant difference between the incidence of catheter-related bacteraemia in the test (n = 0) and control groups (n = 3) (P = 0.2573) . Further prospective studies are required to delineate the role of antiseptic catheters in preventing catheter-related infections. Zoolog Sci, 1996 Feb, 13(1), 111 - 7 Cloning of mRNA sequences for two antibacterial peptides in a hemipteran insect, Riptortus clavatus; Miura K et al.; Escherichia coli injection rapidly induced bactericidal activity in the hemolymph of a hemipteran insect, Riptortus clavatus . This activity reached its maximum at 9 hr after injection and thereafter declined slowly . Two types of cDNA clones involved in this response were isolated by differential screening . The predominant type encoded for an open reading frame of 678 amino acids, which consisted of fourteen tandem repeats . Each repeat was rich in charged residues and had a proline-rich region which had striking sequence similarities to proline-rich antibacterial peptides from other insect species, indicating these clones encode a multipeptide precursor of antibacterial peptides . The other type encoded for a glycine-rich peptide similar to a known antibacterial peptide as well . Northern blot analyses revealed rapid induction of mRNAs corresponding to these clones after the injection . To our knowledge, this is the first report on the mRNA sequences of antibacterial peptides of hemimetabolous insects, and the second report on the occurrence of multipeptide precursor structure in insect antibacterial peptides. Am J Gastroenterol, 1996 Feb, 91(2), 328 - 32 An antibiotic regimen for the treatment of active Crohn's disease: a randomized, controlled clinical trial of metronidazole plus ciprofloxacin; Prantera C et al.; OBJECTIVES: Bacteria in the gut lumen may play a role in the etiology and/or the symptoms of Crohn's disease (CD) . Although various antibacterial drugs have been employed in clinical practice, few controlled trials have been conducted, and those had conflicting results . The aim of this study was to investigate the efficacy and the safety of a combination of metronidazole and ciprofloxacin, compared with methylprednisolone, in treating 41 consecutive patients with active CD . METHODS: Eligible patients, 13 men and 28 women, mean age 38 yr, were randomly allocated to receive, for 12 wk, ciprofloxacin 500 mg twice daily plus metronidazole 250 mg four times daily or methylprednisolone 0.7-l mg/kg/day, with variable tapering to 40 mg, followed by tapering of 4 mg weekly . RESULTS: Ten of the 22 antibiotic patients (45.5%) and 12 of the 19 steroid patients (63%) obtained clinical remission (Crohn's Disease Activity Index < or = 150) at the end of the 12-wk study (p = NS) . Five patients on antibiotics (22.7%) and five patients on steroids (26.3%) were considered treatment failures because of deterioration or persistent symptoms . Six patients receiving antibiotics (27.3%) and two on steroids (10.6%) were withdrawn from the trial because of side effects . One patient on antibiotics was not compliant . CONCLUSIONS: metronidazole and ciprofloxacin could be an alternative to steroids in treating the acute phase of CD. J Med Chem, 1996 Jan 19, 39(2), 446 - 57 The chemistry of Pseudomonic acid . 15 . Synthesis and antibacterial activity of a series of 5-alkyl, 5-alkenyl, and 5-heterosubstituted oxazoles; Brown P et al.; The synthesis of a range of 5-alkyl, 5-alkenyl, and 5-heterosubstituted 2-(1-normon-2-yl) oxazoles is described . The antibacterial activity was determined as the minimum inhibitory concentration against a range of Gram-positive and Gram-negative organisms using a standard Agar dilution procedure . Compounds possessing an acid functionality directly on, or close to, the ring were found to be of greatly decreased potency, while increasing lipophilicity with greater chain length led to increased potency of these derivatives. Antibiot Khimioter, 1996, 41(11), 14 - 7 {The sensitivity of Pseudomonas mallei strains to antibacterial preparations in in-vitro experiments on a cell culture model}; Manzeniuk IN et al.; The cytopathogenic action of P . mallei on macrophages of golden hamsters and transplantable Hep-2 cell culture was studied . It was shown that the culture test systems may be efficient in estimation of the P . mallei virulent properties . The effect of antibacterial drugs on intracellular P . mallei was also studied. Yao Xue Xue Bao, 1996, 31(3), 171 - 5 {Antitumor activity of yungumycin}; Xue YC et al.; Yungumycin, produced by a Streptomyces strain which was isolated from a soil sample collected in Guanping Nature Conservation Zone, Yunnan Province, China, has been verified to be identical with gougerotin . Determined by clonogenic assay, the IC50 of yungumycin to KB cells was found to be 1 microgram.ml-1 . By spermatogonial assay, the activity of yungumycin was very close to that of 5-FU and MTX . Administered by i.p . route, yungumycin showed moderate inhibition against colon carcinoma 26 in mice . However, yungumycin by oral administration exerted highly inhibitory effects on both colon carcinoma 26 and sarcoma 180 (solid tumor) in mice and the inhibition rates reached 85% and 83%, respectively, at tolerable dose . Compared at equitoxic dose of 1/6 LD50, the inhibitory effect of yungumycin (15 mg.kg-1) on sarcoma 180 was similar to that of 5-FU (40 mg.kg-1), showing 72% and 70% tumor inhibition, respectively . Initially, gougerotin was reported as an antibacterial antibiotic without mentioning its antitumor activity . The present studies demonstrate that yungumycin (gougerotin), by oral administration, may be useful in cancer chemotherapy. Vestn Khir Im I I Grek, 1996, 155(6), 17 - 20 {Patient Helicobacter pylori infectivity after gastric resection}; Potashov LV et al.; The article is devoted to investigation of the Helicobacter pylori (HP) infection in 14 patients after resection of the stomach for ulcers of the gastroduodenal zone . Different methods were used for the assessment of the state of the gastric stump and gastroenteric anastomosis in the postoperative period . In most cases different degree of inflammatory alterations of the gastric mucosa were detected . In 2 cases (14.3%) peptic ulcers of the anastomosis developed . Changes to the gastric stump of 11 patients were associated with the HP infection which involved the mucosa of the anastomosed intestine in 8 patients . The data obtained point to possible participation of HP pathogenesis of the alterations detected after the stomach resection . The question of the expediency of a specific antibacterial therapy in the postoperative period and in treatment of certain kinds of postgastroresectional syndromes is raised. Folia Microbiol (Praha), 1996, 41(6), 473 - 6 New azidometalkojates and their biological activity; Hudecova D et al.; Azidometalkojates of the general formula MX2 (M = Cu, Mn, Mg, Zn or Ni and X = 5-hydroxy-2-azidomethyl-4H-pyran-4-one) were prepared and tested for antibacterial, antifungal and cytotoxic effects . The mangan and zinc derivatives are not active against any the tested microorganisms . A weak antibacterial activity was found with the copper derivative . The strongest antifungal effects were shown by the nickel derivative while the highest cytotoxic effect on HeLa cells was manifested by the zinc derivative. Folia Microbiol (Praha), 1996, 41(4), 309 - 14 Porcine interferon-gamma inhibits the growth of Legionella pneumophila in WiREF cells in vitro; Eberl-Gregoric E et al.; The intracellular growth of Legionella pneumophila in WiREF (Wistar rat embryonal fibroblast) cells was inhibited by porcine interferon-gamma . The effect was compared with that of different human interferons (alpha and gamma) . The growth inhibition was dose-dependent and required the pretreatment of WiREF cells with interferon . The development of an antibacterial state of the cells was observed . When interferon was added together with bacteria or 1 d after the infection there was no inhibition . Also, there was no direct antibacterial effect of the interferon . In addition, cell pretreatment with a combination of interferon and antibiotics failed to show a synergistic effect. Polim Med, 1996, 26(3-4), 21 - 8 {Collagen membranes of increased absorption as carriers of antiseptics}; Antiszko M et al.; Collagen membranes of increased absorption were prepared by incubation in the acidic solutions and lyophilization . The organic acids and hydrochloric acid solutions were used for this purpose . The membranes incubated in 2% citric acid possessed of highest absorption . Microdressings containing povidone-iodine or chlorhexidine glycerin solution were prepared using the collagen membranes of increased absorption . The microdressings were packed into envelopes made of laminated aluminium foil; they were stabile for eight weeks concerning their antibacterial activity . After implantation beneath mouse skin the dressings did not cause inflammation . Such dressings may be useful in a treatment of ulcers, superficial burns and chronic granulated wounds. C R Seances Soc Biol Fil, 1996, 190(5-6), 633 - 9 {Study of the membrane oxidative response of phagocytes after treatment with marbofloxacin in healthy cattle}; Spehner V et al.; In addition to their antibacterial properties, quinolones are capable of modulating the immune response . The aim of this paper was to study the effects of a new fluoro-4-quinolone on the respiratory burst . We evaluated the effects of marbofloxacin on the activation of peripheral phagocytes in non-infected bovines after a 5-day treatment . The immunopharmalogical study measured the chemiluminescence response of phagocytic cells obtained from total blood . Serum cortisol and albumin levels were also measured . Data showed that the treatment with marbofloxacin induced a mild decrease in the oxidative response . There was no significant difference between serum albumin levels of normal values and those of before and after treatment, and the levels of serum cortisol were also not significantly different before and after treatment . These results suggest that marbofloxacin treatment could modulate the inflammatory response of phagocytic cells by counteracting the oxidative burst. Vestn Khir Im I I Grek, 1996, (1), 75 - 6 {The use of endolymphatic antibacterial therapy to prevent suppurative complications after heart operations under artificial blood circulation}; Spitsyn PI et al.; Under study were results of antibacterial therapy used in 40 patients with rheumatic heart diseases operated upon under conditions of artificial blood circulation . A conclusion is made that preventive endolymphatic infusion of antibiotics is expedient. Acta Chir Plast, 1996, 38(4), 119 - 21 The influence of progress in the treatment of severe burns on the quality of life; Teich Alasia S et al.; The problems related to burns treatment can be considered among the oldest and most passionating in history of medicine . Since the early forties amazing progresses have been done in the comprehension of the physiopathology of burns . The fast development of resuscitating techniques determined a remarkable reduction of mortality in the first phase; in a similar way through new concepts in the project and construction of intensive care facilities dedicated to burns, where patients can be isolated and a high standard of environmental control can be guaranteed, together with new topical and systemic antibacterial treatment protocols, a significant reduction of infectious complications has been achieved . Concerning surgical treatment early tangential excision and cultured epidermal grafts can be considered the cornerstones of burn therapy . Quality of life of burnt patients have been greatly ameliorated by these technical advances . Burn sequelae however remain the main concern of survivors because of the many controversial aspects of burn scar physiopathology and treatment . Along my career many endeavours I dedicated in this important research field . I will then report the results of most interesting clinical and experimental studies carried out in the last 30 years by our group in collaboration with basic researchers . All the work done in this domain enhance our hope that good results can really improve quality of life in burns: this is the goal for those who dedicated the whole life to relieve the suffering of these badly injured patients. Acta Clin Belg, 1996, 51(6), 386 - 94 {Methods in surgical antibacterial prophylaxis in Belgium, 1992-1995}; Ronveaux O et al.; Since 1992, the Belgian network for the surveillance of nosocomial infections runs a system of voluntary surveillance of surgical wound infections, including the perioperative antibiotic prophylaxis patterns . From 1992 to 1995, the global rate of prophylaxis was 71%, calculated on 44,728 interventions from 72 hospitals, but in 11.4% of operations for which prophylaxis is indicated, it was not given . On the other hand, prophylaxis was prescribed in 55.6% of operations where it was not indicated . At least 4 out of 10 courses were inappropriate with respect to indication, duration or day of administration . Fifteen percent of all courses exceeded 2 days (28% in genitourinary surgery, and 20% in abdominal surgery) . In orthopedic surgery, recommended indications were not followed in 42% of operations . To improve the prescribing of antibiotic prophylaxis in Belgium, local surveillance of prophylaxis patterns and the implementation of guidelines describing good practices should be priorities at the hospital level . At the national level, recommendations about the indications for prophylaxis should be updated and disseminated. Neuropharmacology, 1996, 35(9-10), 1263 - 9 Inhibition of GABAA receptor chloride channel by quinolones and norfloxacin-biphenylacetic acid hybrid compounds; Ito Y et al.; Receptor binding studies have shown that the combination of some new quinolone antibacterial agents with 4-biphenylacetic acid (BPAA), a metabolite of fenbufen, inhibits GABAA receptors . In order to elucidate further the mechanism of these drug interactions, the effect of quinolone antibacterial agents on muscimol-stimulated 36Cl- uptake in rat cerebral cortical synaptoneurosomes was investigated in the absence or presence of BPAA . In the absence of BPAA, quinolones such as norfloxacin (NFLX) and enoxacin attenuated muscimol-stimulated 36Cl- uptake at 10 microM and above . In combination with 10 microM BPAA, the inhibitory effect of these drugs was potentiated and there was a parallel shift of the inhibition curves to the left for these drugs . BPAA alone (1 and 10 microM) did not affect basal or muscimol-stimulated 36Cl- uptake . Hybrid molecules of NFLX and BPAA were synthesized and their inhibitory potency was also investigated . Inhibition curves of muscimol-stimulated 36Cl- uptake revealed that a hybrid with a -CONH(CH2)3- chain between NFLX and BPAA (flexible structure) (1 nM-20 microM) inhibited muscimol-stimulated 36Cl- uptake more potently than did the combination of NFLX (10 nm-100 microM) and 10 microM BPAA . In contrast, another hybrid linked by -CONH-(stretched structure) exhibited a weak inhibitory effect at 10 microM . These results suggest that quinolones in combination with BPAA bind to GABAA receptors, thus inhibiting Cl- channel activity, and that the inhibitory potency of quinolones may be enhanced by an intermolecular interaction with BPAA. Khirurgiia (Sofiia), 1996, 49(3), 37 - 40 {The intensive treatment of children with laparoscopies after ileus peritonitis}; Bogdanova R et al.; Experience gained with the treatment of children undergoing laparostomies, necessitating numerous anesthesias and operative revisions in the early post-operative period, is shared . The open abdominal cavity is the cause of additional loss of liquids, requiring in turn adequate compensation with electrolyte solutions . Early administration of parenteral feeding contributes to prompt postoperative recovery . The active complex management, including antibacterial and immunostimulating therapy, as well as application of hyperbaric oxygenation in the event of severe infection, lead to a favourable outcome. Biomaterials, 1996 Jan, 17(1), 37 - 46 Adsorption/desorption of amine fluorides to hydroxyapatite; Sefton J et al.; This study concerned the adsorption and desorption of commercial amine fluoride (AmF) preparations to hydroxyapatite (HA) . The influence of pH, ionic strength, temperature, saliva and albumin, the latter as a gingival crevicular fluid analogue, on adsorption/desorption was investigated . AmF levels were determined using a surfactant electrode . AmFs 297 and 335 were found to bind immediately and irreversibly to HA in water over a range of pH values, ionic strengths and temperatures, the amounts increasing with concentration . More monovalent AmF 335 was absorbed than divalent AmF 297 . Any AmF desorbed by water from HA was at the lowest end of the minimum inhibitory concentration for oral bacteria . AmF 297 was desorbed by CaCl2, and to a lesser extent by H+, OH-, NH4+, La3+, EDTA, Triton X100 and ethanol, whereas AmF 335 was only slightly desorbed by ethanol . Preadsorption of proteins on HA had little effect on subsequent adsorption or desorption of either AmF . It is postulated that both AmF 297 and AmF 335 are inactivated by an excess of proteins in the surrounding medium, supra- or subgingivally, and not by such proteins preventing or altering the mode or rate of adsorption, or interfering with antibacterial activity, when the AmFs contact a protein-coated tooth surface. Cytobios, 1996, 86(344), 35 - 51 Cell-mediated haemolytic activity of haemolymph from the Colorado potato beetle (Leptinotarsa decemlineata Say.) Glupov VV. Haemolytic activity was identified in cell-free haemolymph from larval and imago stages of Leptinotarsa decemlineata . The haemolytically active fraction of the haemolymph was active against human, sheep, bull, toad and mouse erythrocytes . There was no haemolysis in the presence of 0.001 M EDTA and 0.5% glutathione . The titre of haemolytic activity did not increase after injury or vaccination of the larvae with Microccocus lysodeikticus . Haemolysin, a heat-labile protein was partially purified by ammonium sulphate precipitation, gel filtration, and ion-exchange separation . SDS PAGE, electrophoresis and immunoblotting showed that the active factor was a protein with a molecular weight of approximately 55 kD . It was not bactericidal for various micro-organisms but the antibacterial activity of the lysozyme increased in the presence of haemolysin only when M . lysodeikticus were used as target cells . Spherulocytes synthesized and released the haemolytic protein in vitro . The haemolytic activity increased in the presence of lipopolysaccharide from Escherichia coli and Ca++ ions . The physiological role of the haemolysin is as yet unknown. Acta Biochim Pol, 1996, 43(3), 455 - 65 Porphyromonas gingivalis proteinases in periodontitis, a review; Potempa J et al.; Porphyromonas gingivalis has been closely associated with the initiation and progression of some forms of periodontal diseases and its proteolytic enzymes have been implicated in invasion, tissue destruction and evasion of host antibacterial defenses . Recently, the primary focus of research has been on cysteine proteinases, referred to as gingipain R and gingipain K which are produced in large quantities and are directly involved in pathological events during development and progression of periodontitis, contributing to clinical hallmarks of the disease including: flow of gingival crevicular fluid, neutrophil accumulation and bleeding on probing . Gingipain R exists as 110-, 95-, 70- to 90- and 50-kDa proteins, the first two being a complex of the 50-kDa catalytic subunit with hemagglutinin/adhesins, with or without an added membrane anchorage peptide . The other forms are single-chain enzymes . The predominant form of gingipain K in P . gingivalis strains is a complex of a 60-kDa catalytic protein with hemagglutinin/adhesins . Molecular cloning and structural characterization of the gingipain R and gingipain K genes has shown that they code for 1704 and 1722 amino-acid residue preproenzymes, respectively . Although both structures show no similarity within the preprofragment and only limited identity within the catalytic domain (27%) they are essentially identical within the putative hemagglutinin/adhesin domain . Furthermore, on the basis of gene structure it is now apparent that various soluble and membrane bound forms of gingipains are derived through proteolytic processing of the preproenzymes, and it can be assumed that the Arg-X-specific enzyme is responsible for this processing. Acta Otolaryngol Suppl, 1996, 525, 64 - 7 Transitional concentration of antibacterial agent to the maxillary sinus via a nebuliser; Kondo H et al.; Surface and tissue transitional concentration of 3% FOM aerosol for treatment of paranasal sinusitis was examined in 18 patients (21 sides) who underwent the Caldwell-Luc operation . In this operation, patients have a bony window on the sinus; we therefore investigated the difference of compliance of the maxillary sinus between when we closed the bony window with subcutaneous tissue and when we did it with a silicone sheet before the FOM nebulization . No significance was found in the mean concentration of FOM either at the maxillary sinus surface or in the tissue with or without the use of the silicone sheet . We also examined the concentration using a jet-type nebulizer and an ultra-sonic type nebulizer . Using the ultrasonic-type nebulizer resulted in a higher transitional concentration at two sites of the maxillary sinus surface than when using the jet-type nebulizer . The results suggest that the ultrasonic-type nebulizer is more effective in the treatment of paranasal sinusitis than the jet-type, and that there was no change of maxillary sinus compliance with or without a bony window. Probl Tuberk, 1996, (1), 32 - 5 {Cytokine production during the development and correction of an immunodeficiency in experimental tuberculosis}; Zabolotnykh NV et al.; The authors investigated spontaneous and induced secretion of cytokins at different stages of generalized tuberculosis . In the development of infection there were inhibited IL-2 synthesis in response to ConA, emerging activity of PNO-alpha in response to the inductors in blood serum and culture of peritoneal macrophages, enhanced secretion of IL-6 . Complete immunodeficiency was associated with cessation of IL-2 synthesis by splenocytes, elevated production of IL-6 by peritoneal macrophages, low concentrations of PNO-alpha in the serum and peritoneal macrophage cultures . In the treatment of M . bovis-infected mice with antibacterial drugs alone IL-6 secretion by peritoneal macrophages and PNO-alpha activity in the serum were increased . Immunocorrection resulted in marked activation of IL-2 production by splenocytes in response to ConA as well as enhanced synthesis of IL-6 in unstimulated cultures of peritoneal macrophages. Microbios, 1996, 86(349), 237 - 46 Antibacterial and antifungal activity of ten essential oils in vitro; Pattnaik S et al.; The essential oils of aegle, ageratum, citronella, eucalyptus, geranium, lemongrass, orange, palmarosa, patchouli and peppermint, were tested for antibacterial activity against 22 bacteria, including Gram-positive cocci and rods and Gram-negative rods, and twelve fungi (3 yeast-like and 9 filamentous) by the disc diffusion method . Lemongrass, eucalyptus, peppermint and orange oils were effective against all the 22 bacterial strains . Aegle and palmarosa oils inhibited 21 bacteria; patchouli and ageratum oils inhibited 20 bacteria and citronella and geranium oils were inhibitory to 15 and 12 bacterial strains, respectively . All twelve fungi were inhibited by seven oils (aegle, citronella, geranium, lemongrass, orange, palmarosa and patchouli) . Eucalyptus and peppermint oils were effective against eleven fungi . Ageratum oil was inhibitory to only four fungi tested . The MIC of eucalyptus, lemongrass, palmarosa and peppermint oils ranged from 0.16 to > 20 microliters ml-1 for eighteen bacteria and from 0.25 to 10 microliters ml-1 for twelve fungi. Scand J Infect Dis, 1996, 28(4), 387 - 90 Antimycobacterial synergism of clarithromycin and rifabutin; Ghebremichael S et al.; Clarithromycin and rifabutin are among the most promising drugs for the therapy of infections caused by Mycobacterium avium or other atypical mycobacteria . Since synergism of combined drugs is important in order to achieve strong antimycobacterial activity, the combined inhibitory effects of antibacterial agents should also be investigated when agents are evaluated for possible use in antimycobacterial drug therapy . In the present study we examined the antimycobacterial activity of clarithromycin, rifabutin, and their combination against 51 clinical isolates of the M . avium complex from patients with acquired immune deficiency syndrome (AIDS) with disseminated mycobacteriosis . A concentration-dependent inhibition was seen for each drug . The antibacterial effect was significantly more pronounced for the combined drugs than for the agents tested separately . Synergism, against up to 88% of the strains tested, was seen for the tested drugs combined at different concentrations . All 51 M . avium strains were susceptible to the combination of 4 mg/l clarithromycin and 2 mg/l rifabutin. Korean J Intern Med, 1996 Jan, 11(1), 1 - 8 Helicobacter pylori infection and serum pepsinogen I concentration in peptic ulcer patients: effect of bacterial eradication; Park SM et al.; OBJECTIVES: In order to test the hypothesis that H . pylori infections in the gastric antrum increase pepsinogen I release, fasting serum pepsinogen I concentrations were compared in peptic ulcer patients with and without H . pylori infection . A randomized prospective study was performed to determine whether the increased serum pepsinogen I concentrations associated with H . pylori infection respond to treatment that eradicates H . pylori . METHODS: Fasting serum pepsinogen I concentrations were measured by RIA in 736 patients with endoscopically and histologically confirmed benign peptic ulcer with and without H . pylori infection . Out of 511 patients with H . pylori infection, 110 patients (group 1) were randomly selected and were treated with metronidazole and tripotassium dicitrato bismuthate combined with ranitidine and antacid, and 97 patients (group 2) were treated only with ranitidine and antacid . The third group, 54 patients free of H . pylori infection, was designed to evaluate the influence of H2-receptor antagonist and antacid on the change of pepsinogen I . Fasting pepsinogen I concentration and H . pylori status were compared before and after the treatment . RESULTS: Patients infected by H . pylori (gastric ulcer 208, duodenal ulcer 303; total 511) had significantly higher fasting serum pepsinogen I concentrations than H . pylori negative patients (gastric ulcer 110, duodenal ulcer 115; total 225) . Mean pepsinogen I level of the former was 124.3 +/- 46.9 and that of the latter was 77.9 +/- 25.8 ng/ml . (p < 0.0001) . The difference in serum pepsinogen I concentrations according to the location of ulcer crater was significant only in non-infected subjects e.g., mean pepsinogen I level H . pylori-negative gastric ulcer was significantly lower than that of H . pylori-negative duodenal ulcer patients . H . pylori was eradicated in all the patients who had received antibacterial therapy for 4 weeks and serum pepsinogen I concentrations were significantly decreased from 129.8 +/- 43.0 to 82.4 +/- 24.0 ng/ml after eradication of the organism . (p < 0.0001) In contrast, H . pylori-positive patients who had not received antibacterial therapy were still infected at the completion of the study and there was no significant change in the serum pepsinogen I concentrations after the treatment (120.8 +/- 40.9 vs 126.3 +/- 40.4 ng/ml) . (p > 0.57) None of the patients who were initially H . pylori-negative has been reinfected during the period of the study and their serum pepsinogen I concentrations were not changed . (pre-treatment value 75.1 +/- 8.0; post-treatment value 77.3 +/- 24.5 mg/ml) (p < 0.75) Four-to six-week therapy of H2-receptor antagonist and antacid did not exert any influence on serum pepsinogen I concentrations . CONCLUSIONS: On the basis of our results, we have confirmed that the chronic infection of H . pylori of gastric antrum in peptic ulcer patients causes increased pepsinogen I release into the circulation, and eradication of the organism results in significant fall in serum pepsinogen I concentrations. Drugs Exp Clin Res, 1996, 22(2), 57 - 60 A relationship between serum gentamicin concentrations and minimal inhibitory concentration; Bezirtzoglou E et al.; Since there are few widely accepted guidelines upon which to base therapeutic decisions and adjust for the many variables which may influence the ultimate therapeutic outcome, and few studies have evaluated what the optimal peak concentration-to-MIC ratio should be, pharmacokinetic parameters were estimated from pre- and post-dose concentrations measured in 30 orthopaedic patients, receiving gentamicin . The fluorescence polarization method was used, and simultaneous determination of the MIC (minimal inhibitory concentration) has been made . When Gram(-) microorganisms were incriminated for the infection, the optimal peak concentration exceeded the MIC by more than 3-fold in our serum samples . In Gram(+) bacteria, the peak antibacterial activity usually obtained tended to be lower (between 1.5 and 2) . No correlation was found for the nadir bacteriostatic level . Our investigations showed that the peak bacteriostatic activity correlated well with response to therapy . Based on these findings, the peak antibacterial activity should therefore be between 1.5 and 2 for Gram(+) and greater than 3-fold for Gram(-) microorganisms, and these values seem to be effective for eradication of the infection. Chin J Biotechnol, 1996, 12(1), 1 - 7 Gene localization and expression of thienamycin cyclase gene in Streptomyces lividans TK24; Li R et al.; Transformants of S . lividans TK24 were obtained by transforming a recombinant plasmid p6BC12 harboring the thienamycin cyclase gene into it . An antibacterial substance could be detected by the conversion of fermentation broth of the Y3 block mutant and the purified Y3 mutant intermediate with a cell-free extract of S . lividans TK24 transformant . Paper chromatographic analysis showed that the conversion product of Y3 fermentation broth with cell-free extract of S . lividans TK24 was thienamycin and an unstable antibacterial substance was a product of Y3 intermediate with cell-free extract of the transformants . This result indicated that the thienamycin cyclase gene was expressed in S . lividans TK24 and complemented the deficiency in the Y3 block mutant . Restriction analysis of p6BC12 was carried out and the restriction map was constructed . The thienamycin cyclase gene was localized on a 0.9 kb PstI-HinCII fragment from a bioconversion result . The 1.0 kb IPNS homologous DNA fragment in plasmid p6BC12 was excluded from the cyclase activity. Drugs, 1996, 52 Suppl 2, 9 - 17 The inflammatory cytokines . New developments in the pathophysiology and treatment of septic shock; Glauser MP; Bacterial products {lipopolysaccharide (LPS) with Gram-negative bacteria and toxins, superantigens or cell wall fragments with Gram-positive bacteria} are the main activators of the septic shock cascade . These molecules interact with monocytes, macrophages and endothelial cells to produce inflammatory cytokines {tumour necrosis factor (TNF) and interleukins 1 and 6}, and may activate other harmful pathways such as the coagulation system, complement cascade and lipid mediators . As a therapeutic strategy, antibodies directed against LPS have been well studied, although, on the whole, the clinical results have been disappointing . Other possible interventions that have not yet been tested clinically include natural intracellular antibacterial proteins (e.g . bacterial permeability-increasing protein) and high density lipoprotein (responsible for detoxifying LPS in the body) . The stimulation pathway of responsive cells by bacterial products is also another possible target for intervention . Compounds under investigation include soluble CD14 and antibodies directed against CD14 or LPS binding protein . Antibodies directed against the cytokines are another option . Anti-TNF antibodies are currently being investigated, but conclusive evidence of their activity is still lacking . Soluble receptors (e.g . interleukin-1 receptor antagonist, or soluble TNF receptor) are another possibility; one soluble TNF receptor is still undergoing clinical investigation. Adv Enzyme Regul, 1996, 36, 267 - 81 Inhibition of experimental metastasis by enzyme inhibitors from microorganisms and plants; Umezawa K; Various antibacterial compounds, antitumor compounds, enzyme inhibitors and recent signal transduction inhibitors have been discovered from microorganisms and plants . Therefore, it should be possible to find antimetastatic compounds from these sources, if a simple assay system is available . We isolated several enzyme inhibitors from nature to inhibit experimental metastasis . Leupeptin is an old protease inhibitor and inhibited blood-borne lung metastasis of hepatoma cells in rats . A leupeptin analogue inhibiting urokinase inhibited in vitro invasion of human fibrosarcoma cells . Alpha-glucosidase inhibitors such as epi-CPL and baicalein inhibited in vitro invasion and in vivo metastasis of mouse melanoma cells . A mannosidase inhibitor, mannostatin A, also inhibited in vitro invasion of mouse melanoma cells . Oncogene function inhibitors induce normal phenotypes in the oncogene-expressing cells . As expected, they inhibited tumor cell invasion in vitro. Eur J Clin Pharmacol, 1996, 49(5), 407 - 9 Estimation of steady state antibiotic concentration in cerebrospinal fluid from single-dose kinetics; Nau R et al.; OBJECTIVE: Assuming linear kinetics, the mean CSF concentrations of an antibacterial in steady state (CssCSF) can be estimated, when the area under the concentration-time curve in CSF after the first dose is known . For this purpose we propose the function CssCSF = AUCCSF.Anticipated dose/Dosing Interval.Applied dose . RESULTS: Together with the MIC and MBC of the causative pathogen, the estimate is of value in the choice of antibacterial drug and the dosing regimen in central nervous system infections. Angle Orthod, 1996, 66(4), 313 - 6 Effect of applying chlorhexidine antibacterial agent on the shear bond strength of orthodontic brackets; Bishara SE et al.; The purpose of this study was to determine whether the application of chlorhexidine as an anti