Antimicrobials

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 antibacterial agent affects the shear bond strength and debonding failure modes of orthodontic brackets . Thirty-six recently extracted human premolars were cleaned and randomly assigned to one of three groups: prophylaxis with pumice only prophylaxis using a 13,500 ppm fluoridated pumice, and prophylaxis with pumice followed by application of 0.12% chlorhexidine paste . All teeth were etched with a 37% phosphoric acid gel and metal orthodontic brackets were bonded to each tooth using the same bonding system . The teeth were mounted in phenolic rings and stored in deionized water at 37 degrees C for 72 hours . A Zwick Universal Testing Machine was used to determine shear bond strengths . The residual adhesive on the enamel surfaces was estimated using the Adhesive Remnant Index . The analysis of variance was used to compare the various groups . Significance was predetermined at P < 0.05 . The results indicated that there were no significant differences in bond strengths between the chlorhexidine-, fluoride-, and nonfluoride-treated teeth (P = 0.233) . The Chi-Square test evaluating the residual adhesive on the enamel surfaces also showed no significant differences (P = 0.456) between the various groups . In conclusion, the use of chlorhexidine and/or fluoride prophylactic pastes does not significantly affect shear bond strength nor bond failure location of orthodontic brackets.

Pol J Pathol, 1996, 47(2), 57 - 63
Non-ulcer dyspepsia and Helicobacter pylori infection--morphological analysis according to the Sydney system--changes before and after treatment; Lewy-Trenda I et al.; Non-ulcer dyspepsia (NUD) means the presence of upper abdominal pain and discomfort and also nausea, vomiting, flatulence, heartburn and belching . It is estimated, that about 20-30% of all patients refer to a doctor because of dyspeptic symptoms . Helicobacter pylori (Hp) infections are diagnosed in about 60% of persons with NUD and in 80-100% of patients with clinical, endoscopic and histological diagnosis of gastritis . The authors decided to investigate a correlation between gastritis and Hp infection and a relationship between the influence of antibacterial therapy and Hp eradication from gastric mucus and to observe gastric mucosa condition . We examined 73 patients (range age 16-73): 40 females and 33 males . We employed the Sydney System for evaluation of gastric mucosa condition . The patients were divided into two groups: Hp-positive 50 persons and Hp-negative-23 persons . Hp infected subjects were treated with antibacterial drugs (bismuth + metronidazol + amoxycillin or bismuth + metronidazol + tetracycline) and Hp-negative only with bismuth . Hp eradication was obtained in 72.7% of patients treated with bismuth + metronidazol + amoxycillin and 76.4% of persons treated with bismuth + metronidazol + tetracycline . A statistically significant difference between these two kinds of antibacterial therapy was not noted . Both methods are equally effective . We observed also and improvement of the histological state of antrum and corpus gastric mucosa after therapy in comparison to changes before treatment . We noticed a decrease of dyspeptic complaint in 89.2% of Hp infected persons in whom Hp had been eradicated . Among Hp-negative 23 patients gastric mucosa was normal in 30% and chronic gastritis was found in 70% of subjects . Based upon the present results it seems very important and suitable to detect Hp organisms in gastric mucus of all dyspeptic patients who are endoscopically examined and biopsied at the same time . We would suggest to do an urease test and to take histological samples together with full endoscopic examination according to the Sydney System guidelines.

Gynecol Obstet Invest, 1996, 42(1), 24 - 7
Amniotic fluid antibacterial activity and nutritional parameters in term Mozambican and Swedish pregnant women; Axemo P et al.; Randomly selected parturients with term singleton pregnancies from two different settings, 83 from Mozambique and 90 from Sweden, entered the study . All of them underwent elective cesarean section, which enabled sterile harvesting of amniotic fluid (AF) . AF samples were then tested for antibacterial activity (ABA) . Background data and nutritional status were compared . Average age was 32.7 and 30.7 years (n.s.), average parity 6.6 and 1.6 (p < 0.0001), average number of antenatal visits 4.9 and 11.6 (p < 0.0001), and average birthweight 3,194 and 3,688 g (p < 0.01), respectively . Body mass index, mid-upper-arm circumference and hemoglobin did not show any significant differences . The average ABA of AF was more than 50% higher in Swedish than in Mozambican specimens (p < 0.0001) . Less than one-sixth of MoZambican women reached the average ABA of AF from Swedish women . Bacterial outgrowth delay equal to or above 3 h was encountered in 13% of Mozambican AF as against 61% of Swedish AF (OR 0.10; 95% CI 0.05-0.19) . Histopathological examinations of the placenta, nonplacental membranes and umbilical cord showed inflammatory lesions in 29% of the Mozambican parturients and in 13% of Swedish parurients (OR 2.65; 95% 1.00-6.98) . It is probable that the lower antibacterial activity in Mozambican AFs reflects an increased vulnerability to ascending genital infections during late pregnancy.

Zh Mikrobiol Epidemiol Immunobiol, 1996 Jan-Feb, (1), 7 - 10
{The resistance of Francisella tularensis to the bactericidal action of normal serum as a criterion for evaluating the virulence of the bacterium}; Pavlovich NV et al.; The study of the sensitivity of F . tularensis to the bactericidal action of normal serum (NS) revealed that all virulent cultures were resistant, while avirulent cultures were highly sensitive to NS . The synthesis of R-lipopolysaccharide (LPS) by capsule-deficient (Cap-) clones or the synthesis of S-LPS by capsule-defective (Cap+/-) clones of the avirulent phenotype of these bacteria had no influence on the sensitivity of these forms to NS, but ensured longer survival of Cap+/- variants in the serum in comparison with Cap- cells . The antibacterial activity of NS with respect to avirulent strains was determined by the system of the complement, activated following the classical route . Only complete S-LPS characteristic of virulent strains was capable of preventing the sorption of components and the assembly of the complement on the surface of bacteria, while defective forms of LPS of avirulent strains did not protect serosensitive receptors from interaction with the complement . The opsonization of Cap+/- virulent and Cap- avirulent bacteria with tularemic antibodies did not alter {correction of after} their reaction to incubation with NS, but ensured the survival of Cap+ forms for more than 24 hours.

Annu Rev Biochem, 1996, 65, 215 - 39
Molecular mechanisms of drug resistance in Mycobacterium tuberculosis; Blanchard JS; In spite of forty years of effective chemotherapy for tuberculosis, the molecular mechanisms of antibacterial compounds in Mycobacterium tuberculosis have only recently been revealed . Broad spectrum antibacterials, including streptomycin, rifampicin, and fluoroquinolones have been demonstrated to act on the same targets in M . tuberculosis as they do in E . coli . Resistance to these agents results from single mutagenic events that lead to amino acid substitutions in their target proteins . The mechanisms of action of the unique antitubercular drugs, including isoniazid, ethambutol, and pyrazinamide have also recently been defined . Resistance to isoniazid can be caused either by mutations in the katG-encoded catalase-peroxidase, the enzyme responsible for drug activation, or by the molecular target, the inhA-encoded long chain enoyl-ACP reductase . Ethambutol appears to block specifically the biosynthesis of the arabinogalactan component of the mycobacterial cell envelope, and pyrazinamide has no known target . With the resurgence of tuberculosis and the appearance of strains which are multiply resistant to the above compounds, present tuberculosis chemotherapies are threatened . New approaches to the treatment of multi drug-resistant tuberculosis are needed.

Antimicrob Agents Chemother, 1996 Jan, 40(1), 274 - 7
Antibacterial activity and pharmacokinetics of four new 7-azetidinyl fluoroquinolones; Coll R et al.; The activity of E-4535, E-4534, E-4528, and E-4527, four new 7-azetidinyl-6-fluoroquinolones, was studied to evaluate the role played by the C-2' and C-3' substitutions of the azetidinyl group, together with a C-8 fluorine atom . In general, like other 6,8-difluoroquinolones, E-4534 and E-4527 showed higher levels of activity than the corresponding monofluorinated derivatives, E-4535 and E-4528 . E-4535 and E-4534, having a 7-(2-methyl-3-aminoazetidinyl) substituent, demonstrated higher levels of activity in vitro than their corresponding structural analogs, E-4528 and E-4527, distinguished by a 3-methyl-3-methylaminoazetidinyl group at position 7 of the quinolone nucleus . In consequence, E-4534 was the most potent of the new agents tested.

EXS, 1996, 75, 347 - 61
Molecular evolution of ruminant lysozymes; Irwin DM; The evolution of a new digestive enzyme, stomach lysozyme, from an antibacterial host defense enzyme provides a link between molecular evolution and organismal evolution . Lysozymes have been recruited at least three times (twice from a conventional lysozyme c and once from a calcium-binding lysozyme c) in vertebrates for functioning in the stomach . The recruitment of lysozyme for its new biological function involved many molecular changes, beyond those required to adapt the protein to function in the stomach . The evolution of the stomach lysozyme gene has been extensively studied in ruminant artiodactyls . In ruminants, the lysozyme c gene has duplicated to yield a family of about ten genes . These duplications allowed: (1) specialization of gene function and (2) increased levels of expression . The ruminant stomach lysozyme genes have evolved in an episodic fashion - there was a period of rapid adaptive sequence evolution, driven by positive selection in the early ruminant, that was followed by an increase in purifying selection upon the well-adapted stomach lysozyme sequence among modern species . Recombination of small portions (exons) of the genes between members of the lysozyme gene family may have aided in adaptive evolution . Evolution to a stomach lysozyme is not irreversible; at least one member of the ruminant stomach lysozyme gene family appears to have reverted to a more ancestral function, yet retains hallmarks of its history as a stomach lysozyme.

Zhonghua Zheng Xing Shao Shang Wai Ke Za Zhi, 1996 Jan, 12(1), 15 - 8
{Experimental study on antibacterial activity of subdermal vascular network island skin flap}; Yang Y et al.; A comparison study was carried out on the antibacterial activity between two kinds of pig buttock flaps: the conventional island skin flap and the subdermal vascular network island skin flap which was created by thinning the distal half of a conventional island flap, preserving its subdermal vascular network . Antibacterial activity was evaluated by bacterial counts, phagocytic index and intracellular bacterial killing ratio of leukocytes, skin temperature, laser Doppler, ink perfusion, microangiography and transparent specimen technique . The results indicated that antibacterial activity of the subdermal vascular network island skin flap was much lower than that of the conventional island skin flap . The reduced blood supply and decreased leukocyte function were responsible for the low antibacterial activity after the conventional island flap was thinned.

Khirurgiia (Mosk), 1996, (2), 5 - 7
{Method of pancreatoduodenal resection and intraoperative prevention of acute pancreatitis}; Buianov VM et al.; In the period from 1988 to 1991 the authors carried out 27 pancreatoduodenal resections with 11.1% mortality . From analysis of the results they formulated the main technical principles of this operation and suggested a complex of intraoperative measures for prevention of acute postoperative pancreatitis . The complex included application of a 5-fluorouracil-containing covering of the pancreas at the stage of exposure of the complex which will be removed; individualization of the methods for treatment of the pancreatic stump depending on the diameter of the pancreatic duct; the use of prolene in forming the pancreaticoenteroanastomosis; intraoperative administration of cephalosporins and dioxidine followed by antibacterial therapy; application of microsphere with cytostatics to the pancreas at the operation end for prolongation of pancreatic secretion suppression.

Probl Tuberk, 1996, (3), 38 - 9
{Immunological indicators in patients with pulmonary tuberculosis in the presence of drug-resistant Mycobacteria}; Kuz'mina NV; Immunological indices for 121 pulmonary tuberculosis (PT) patients discharging drug-resistant M . tuberculosis were compared to those for 87 PT patients with M . tuberculosis sensitive to antibacterial drugs . The patients with drug-resistant bacteria before hospitalization had lower count of T-lymphocytes, altered proportion T-helpers/T-suppressors, reduced ability of T-lymphocytes for blast transformation in the presence of PHA and PPD . T-lymphocyte functional activity remained inhibited as compared to those patients discharging drug-sensitive mycobacteria.

Arch Dermatol Res, 1996, 288(1), 45 - 50
Sparfloxacin phototoxicity: potential photoaugmentation by ultraviolet A and B sources; Tokura Y et al.; Sparfloxacin, a quinolone antibacterial agent, frequently elicits photosensitive skin reactions . Our clinical studies of patients treated with sparfloxacin have demonstrated that this photosensitivity is primarily phototoxic and that a marked erythematous response is induced by sequential irradiation with ultraviolet A (UVA) and B (UVB) but not UVA or UVB alone, suggesting potential synergism between UVA and UVB . We evaluated the phototoxicity of this agent using in vitro DNA breaking activity and in vivo murine cutaneous responses . Sparfloxacin induced DNA strand breaks in vitro and converted the supercoiled closed circular form of plasmid DNA to the open circular form by its photodynamic action . In mice, the topical application of sparfloxacin and subsequent irradiation with UVB, but not UVA, induced ear swelling responses . However, the UVB-induced ear swelling response was augmented by irradiation with UVA before or after UVB exposure . Such interaction between UVA and UVB in the production of ear swelling was further confirmed by systemic administration of sparfloxacin . Our study suggests that sparfloxacin is a unique phototoxic agent in that photosensitivity dermatitis is evoked by photoaugmentation between UVA and UVB.

Drugs, 1996 Jan, 51(1), 161 - 78
Clarithromycin and omeprazole as helicobacter pylori eradication therapy in patients with H . pylori-associated gastric disorders; Markham A et al.; Helicobacter pylori is susceptible to many antibacterial drugs in vitro but has proved difficult to eradicate in vivo . The macrolide clarithromycin has good activity against H . pylori in vitro and has demonstrated the highest eradication rate for any antibacterial monotherapy in vivo . However, it is clear that antibacterial monotherapy is not a sufficiently effective treatment for patients with H . pylori infection . The suggestion that high intragastric acidity impairs the action of antibacterial drugs led to the evaluation of combination H . pylori eradication regimens including H+,K+-ATPase inhibitors and antibacterial drug(s) with or without bismuth compounds . Noncomparative studies evaluating the efficacy of dual therapy with clarithromycin plus omeprazole in patients with H . pylori infection have reported eradication rates of between 58 and 83% > or = 4-weeks after therapy . In comparative studies, clarithromycin plus omeprazole was at least as effective as amoxicillin plus omeprazole . However, direct comparisons have shown that eradication rates achieved by dual therapy are not as high as those achieved by triple therapy . Indeed, triple therapy with clarithromycin plus omeprazole in combination with amoxicillin or a nitroimidazole has achieved eradication rates of up to 100% . Although 14-day triple drug regimes were initially considered necessary for effective eradication, it now seems clear that 7-day regimes are equally effective . Factors known to influence response to H . pylori eradication therapy include bacterial resistance and patient compliance . A review of 4 studies evaluating the efficacy of dual eradication therapy with clarithromycin plus omeprazole reported an overall incidence of adverse events (patient or investigator reported, whether related to treatment or not) of 45% . The most common adverse event was taste disturbance (an adverse event commonly reported during the development of clarithromycin); nausea, headache, diarrhoea, vomiting and abdominal pain occurred less frequently . Although dual therapy might be expected to cause fewer adverse events than triple therapy this has not been the case in direct comparisons conducted to date . Thus, although clarithromycin plus omeprazole is associated with an H . pylori eradication rate of approximately 70%, 1 week of triple therapy with these 2 drugs together with amoxicillin or a nitroimidazole, which eradicates the organism in approximately 90% of cases, may represent optimal H . pylori eradication therapy.

Drugs, 1996, 51 Suppl 1, 13 - 9
Streptogramins . A unique class of antibiotics; Pechere JC; Streptogramin antibiotics represent a unique class of antibacterials in that each member of the class consists of at least 2 structurally unrelated molecules: group A streptogramins (macrolactones) and group B streptogramins (cyclic hexadepsipeptides) . Both group A and group B streptogramins inhibit protein synthesis at the ribosomal level, and they act synergistically against many isolates, their combination generating bactericidal activities and reducing the possibility of emergence of resistant strains . The mechanisms of acquired resistance to group B streptogramins are similar to those induced by erythromycin, but group A streptogramins remain unaffected by target modifications and active efflux . The pharmacokinetic parameters of group A and group B streptogramins in blood are quite similar . In addition, both the A and B groups penetrate and accumulate in macrophages and in the bacterial vegetations of experimental endocarditis . There are important structural and biological differences between the streptogramins and the macrolides . The main differentiating features are the rapid anti-bacterial killing of streptogramins and the rarity of cross-resistance between the 2 groups of antibiotics.

Acta Haematol, 1996, 96(2), 64 - 7
Short-course intravenous antibiotics with oral quinolone prophylaxis in the treatment of neutropenic fever in autologous bone marrow or peripheral blood progenitor cell transplant recipients; Mahendra P et al.; The effectiveness of short-course intravenous antibiotics concurrent with prophylactic oral ciprofloxacin in the treatment of neutropenic fever was studied in 81 patients undergoing autologous bone marrow or peripheral blood progenitor cell transplantation (ABMT or PBPCT) . During the neutropenic period following ABMT or PBPCT, 10/81 (12%) patients did not require treatment with intravenous antibiotics . Seventy-one patients required antibiotics . Forty-seven of the 71 (66%) responded to 72 h treatment with gentamicin, azlocillin or ceftazidime, and vancomycin . Thirty-three of the 47 (70%) responders had a complete resolution of their fever with no further recurrence . Fourteen of the 47 responders developed a second fever between 2 and 25 days after stopping first-line antibiotics . Eleven of the 14 patients responded to a second course of intravenous antibiotics . Twenty-four of the 71 patients did not respond to intravenous antibiotics and were treated with intravenous amphotericin and the intravenous antibacterial agents were discontinued . Eighteen of the 24 patients responded to amphotericin . The 6 patients who had persistent fever resolved their temperature when their neutrophil count recovered . There were no deaths due to infection during the study . Short-duration intravenous antibiotics in conjuction with oral ciprofloxacin prophylaxis are a safe and effective treatment for neutropenic fever.

Clin Exp Dermatol, 1996 Jan, 21(1), 46 - 7
Photosensitivity induced by fleroxacin; Kimura M et al.; A case of photosensitivity induced by fleroxacin (FLRX) is reported . A 71-year-old man had erythema on sun-exposed areas after 5 months FLRX treatment for prostatitis . The minimal erythema dose to UVA was reduced at the initial examination and became normal 4 weeks after he stopped taking FLRX . Oral photo-challenge with FLRX 100 mg was positive, but photopatch testing was negative . Fleroxacin (FLRX), in use since 1992, is a fluoroquinolone antibacterial derived from quinoline . Photosensitivity induced by FLRX is not uncommon, but a photobiological study has not been reported . The mechanism of action of photosensitivity induced by the fluoroquinolones is considered to be phototoxic in origin in that in vitro technique studies are positive . FLRX, a quinoline derivative may be a photosensitizer as well as enoxacin, lomefloxacin and sparfloxacin.

Bioorg Med Chem, 1996 Jan, 4(1), 61 - 71
Using SAR and QSAR analysis to model the activity and structure of the quinolone-DNA complex; Llorente B et al.; A set of 78 quinolone derivatives were used in a structure-activity study to identify structural features correlating with antibacterial activity . Distinct combinations of functional properties were identified for Gram-negative and Gram-positive bacteria . 3-D Quantitative structure-activity relationship (QSAR) studies identified specific hydrophobic, topologic and electronic properties of the molecules for both in vitro and in vivo activities . From these results, a three-dimensional model of a DNA-quinolone complex was built using molecular modeling techniques . It was based on the intercalation of quinolone into the double helix of DNA . We conclude that the intercalation model is consistent with most available data on the structure of the quinolone complex . This predicted structure is stabilized by the binding of magnesium ion with the sp2 oxygens present in quinolone, a phosphate and a purine base of the DNA . Substituents R1 and R7 are predicted to make hydrophobic interactions in the major and minor groove of DNA, respectively . R7 could also form hydrogen bonds with amino groups of guanines and the aspartic acid residue at position 87 in DNA gyrase subunit A.

Vopr Kurortol Fizioter Lech Fiz Kult, 1996 Jan-Feb, (1), 21 - 2
{Tubal pregnancy: the experience of early rehabilitative treatment}; Strugatskii VM et al.; The surgical treatment for tubal pregnancy including laparoscopy and antibacterial therapy were combined in 30 females with early start (on postoperative day 1) of rehabilitation: psychotherapy, diet, therapeutic exercise, low-frequency magnetotherapy . Hysterosalpingography and dynamic dopplerography assessed the effect as good.

Hepatogastroenterology, 1996 Jan-Feb, 43(7), 306 - 8
A randomized trial of pefloxacin plus klindamicin and cefoxitin in hepatobiliary and pancreatic surgery; Fried M et al.; BACKGROUND/AIMS: The efficacy and safety of pefloxacin plus klindamicin with cefoxitin were studied in patients undergoing hepatobiliary or pancreatic surgery . MATERIALS AND METHODS: Seventy-five patients with biliary tract, hepatic, or pancreatic pathology were randomly allocated in a prospective open study to receive a combination of either i.v or oral pefloxacin (800mg per day) plus klindamicin (2,400mg per day) or an i.v . cefoxitin (4,000mg per day) . RESULTS: Twenty patients had to be withdrawn from the trial because of negative baseline culture or because of isolation of bacteria resistant to the study drugs . In the remaining fifty-five patients, the clinical cure rates were excellent in more than ninety five percent and similar for both groups, the bacteriological success rates were 100% in the pefloxacin plus klindamicin group and 89.1% in the cefoxitin group . No patients were withdrawn from the study because of side effects . CONCLUSION: In our study we have shown the excellent results of the antibacterial therapy with pefloxacin and klindamicin of the patients who underwent complicated hepatobiliary and pancreatic surgery.

J Dairy Sci, 1996 Jan, 79(1), 76 - 82
Mastitis-causing Escherichia coli: serum sensitivity and susceptibility to selected antibacterials in milk; Fang W et al.; A total of 169 Escherichia coli strains were isolated from cows with cases of clinical mastitis . beta-Glucuronidase production, serum sensitivity, and susceptibility to selected antibacterials were analyzed using the fluorometric beta-glucuronidase assay . About 89% (150 of 169) of the isolates tested positive for beta-glucuronidase . Of these isolates producing beta-glucuronidase, 102 (68%) were resistant or moderately resistant to bovine serum . The antibacterial susceptibility of 96 isolates was tested in broth and milk . There was a significant shift from lower fluorometric minimum inhibitory concentration for tetracycline, sulfadoxin-trimethoprim, enrofloxacin, and gentamicin in broth to higher fluorometric minimum inhibitory concentration in milk . Serum sensitivity and susceptibility to tested antibacterials in broth or in milk were not related . Gentamicin and sulfadoxin-trimethoprim seemed to be more potent in mastitic milk than in normal milk, suggesting a possible synergistic effect between these exogenous antibacterials and the indigenous antibacterial agents in mastitic milk.

Pharm Res, 1996 Jan, 13(1), 70 - 5
Acyloxymethyl as a drug protecting group . Part 3 . Tertiary O-amidomethyl esters of penicillin G: chemical hydrolysis and anti-bacterial activity; Moreira R et al.; PURPOSE . O-(N-alkylamido)methyl esters of penicillin G were studied as a new class of prodrugs . METHODS . The hydrolysis in aqueous buffers containing 20 % (v/v) of acetonitrile was investigated by HPLC . RESULTS . A U-shaped pH-rate profile was seen with a pH-independent process extending from pH ca . 2 to pH ca . 10 . This pathway is characterised by kinetic data that are consistent with a unimolecular mechanism involving rate-limiting iminium ion formation and penicillinoate expulsion . Penicillin G and the corresponding amide are the ultimate products detected and isolated, indicating that beta-lactam ring opening is much slower than ester hydrolysis . The O-(N-alkylamido)methyl esters of penicillin G displayed similar in vitro antibacterial activity to penicillin G itself . CONCLUSIONS . Compared to the penicillin G derivatives, the much higher stability of the O-(N-methylbenzamido)methyl benzoate, acetate and valproate esters (which gave rise to a Bronsted Beta 1g value of ca . -1) suggests that tertiary N-acyloxymethylamides may be useful prodrugs for carboxylic acid drugs with pKa > 4.

Comp Immunol Microbiol Infect Dis, 1996 Jan, 19(1), 47 - 53
Some biochemical responses of buffalo PMN cells to various stimuli; Sarmah S et al.; In view of great species differences in biology of polymorphonuclear cells, and non-availability of basic data on buffalo PMN cells for assessing their functional activity, the present work on the immuno-defence system involving protein synthesis and O2- production was undertaken to highlight the immunomodulatory role of thyroxine . Digitonin, LPS and Con-A activation generated superoxide, which was monitored by NBT reduction . The study suggested that concanvalin A (Con-A) and T4 were able to synergetically increase the production of superoxide and H2O2 . The likely involvement of thyroxine in activation was studied by {125I}thyroxine incorporation, which was significantly increased due to activation . In contrast, aflatoxin B1 together with Con-A caused a significant decrease (P < 0.05) in incorporation of {125I}T4 . Optimum time dependence in {14C}leucine incorporation by buffalo PMN cells was found to be 30 min and the factors like T4 (7.7 ng/ml) and glutathione (400 micrograms/ml) significantly enhanced the incorporation . In contrast, antiinflammatory agent, indomethacin (40 micrograms/ml) inhibited protein synthesis in PMN cells; while puramycin also significantly lowered the {14C}leucine incorporation . Total {14C}leucine incorporation in acid extractable cationic proteins and peptides, known for their antibacterial properties was found to be 30-40% when separated on AU-PAGE . The studies revealed the in vitro immunomodulatory role of T4 in O2-, H2O2 production and cationic protein synthesis by the activated PMN cells of buffalos.

Vestn Ross Akad Med Nauk, 1996, (2), 49 - 52
{Microbiological diagnosis and antibacterial therapy of non spore-forming anaerobic infections in emergencies}; Zubkov MN et al.; A total of 240 patients with soft tissue and wound suppurations, peritonitis, and suspected sepsis were examined . Anaerobic isolates were more frequently obtained in 20-75% of patients infections associated with facultative microbes . The use of non-culture media (bacterioscopy and gas-liquid chromatography) increased the detection rate of anaerobic infection up to 82% as compared with bacteriological diagnosis (63%) . The findings and the data of monitoring of suppuration agents for several years allowed the authors to work out effective combined treatment regimes for early mixed aerobic and anaerobic infections in 80-100% of patients.

J Antimicrob Chemother, 1996 Jan, 37(1), 45 - 52
Susceptibility of Helicobacter pylori to simethicone and other non-antibiotic drugs; Ansorg R et al.; The antifoaming agent simethicone (Lefax), the protease inhibitor gabexate mesilate (FOY), the antimycotic ketoconazole, and the hydroxyl scavangers dimethylsulphoxide (DMSO) and allopurinol were investigated for growth inhibition of Helicobacter pylori and representative strains of other bacterial species . H . pylori were selectively inhibited by 64-128 mg/L of simethicone, 64-128 mg/L gabexate mesilate, and 16-64 mg/L ketoconazole . Dimethylsulphoxide and allopurinol showed no antibacterial effect at concentrations used therapeutically . It is concluded that gabexate mesilate, ketoconazole and, particularly, simethicone are candidates for treatment of H . pylori infection.

J Endod, 1996 Jan, 22(1), 27 - 9
Root canal irrigation with citric acid solution; Yamaguchi M et al.; The purpose of this study was to investigate various properties of citric acid and EDTA solution as decalcifying and cleansing agents in root canal irrigation, and antibacterial effects of citric acid and EDTA solution . Powdered dentin-resin mixtures were used for evaluating the decalcifying effect of citric acid and EDTA solution . Twelve bacterial strains isolated from infected root canals, were used to evaluate the antibacterial effects of citric acid and EDTA solution . Powdered dentin-resin mixture was found to be more soluble in a 0.5, 1, and 2 M citric acid solutions than in a 0.5 M EDTA solution . Citric acid solution showed antibacterial effects on all the bacteria used.

Am J Ophthalmol, 1996 Jan, 121(1), 89 - 91
Diagnosis of microsporidial keratitis by confocal microscopy and the chromatrope stain; Shah GK et al.; PURPOSE: To illustrate the value of confocal microscopy and chromatrope stain in the diagnosis of microsporidial keratitis . METHODS: In vivo confocal microscopy was performed on a man with the human immunodeficiency virus who had severe bilateral epithelial keratitis refractory to topical antibacterial medications . The results were compared to conjunctival scrapings stained with the chromatrope-based Weber stain . RESULTS: Confocal microscopy demonstrated many small, intraepithelial opacities of the corneal epithelium, which were suggestive of Microsporidia . Results of the chromatrope stain of conjunctival scrapings confirmed the diagnosis of microsporidial keratitis . CONCLUSIONS: Rapid diagnosis allowed prompt initiation of topical fumagillin, which permitted rapid, long-term control of the symptoms of microsporidial keratitis.

FEBS Lett, 1995 Dec 27, 377(3), 373 - 6
Molecular cloning of the defense factor in the albumen gland of the sea hare Aplysia kurodai; Takamatsu N et al.; Aplysianin-A, an antibacterial glycoprotein in the albumen gland of the sea hare Aplysia kurodai, inhibited the growth of both Gram-positive and Gram-negative bacteria . Aplysianin-A cDNA clones were isolated from an albumen gland cDNA library . Sequence analysis reveals that aplysianin-A is produced as a precursor protein of 556 amino acid residues with a signal peptide of 19 amino acid residues and contains 6 potential N-glycosylation sites . Aplysianin-A mRNA was expressed tissue-specifically in the albumen gland . Homology search reveals that aplysianin-A has a 50% overall amino acid sequence homology to achacin, an antibacterial glycoprotein of the giant African snail Achatina fulica.

N Engl J Med, 1995 Dec 14, 333(24), 1600 - 7
Medication use and the risk of Stevens-Johnson syndrome or toxic epidermal necrolysis; Roujeau JC et al.; BACKGROUND . Toxic epidermal necrolysis and Stevens-Johnson syndrome are rare, life-threatening, drug-induced cutaneous reactions . We conducted a case-control study to quantify the risks associated with the use of specific drugs . METHODS . Data were obtained through surveillance networks in France, Germany, Italy, and Portugal . Drug use before the onset of disease was compared in 245 people who were hospitalized because of toxic epidermal necrolysis or Stevens-Johnson syndrome and 1147 patients hospitalized for other reasons (controls) . Crude relative risks were calculated and adjusted for confounding by multivariate methods when numbers were large enough . RESULTS . Among drugs usually used for short periods, the risks were increased for trimethoprim-sulfamethoxazole and other sulfonamide antibiotics (crude relative risk, 172; 95 percent confidence interval, 75 to 396), chlormezanone (crude relative risk, 62; 21 to 188), aminopenicillins (multivariate relative risk, 6.7; 2.5 to 18), quinolones (multivariate relative risk, 10; 2.6 to 38), and cephalosporins (multivariate relative risk, 14; 3.2 to 59) . For acetaminophen, the multivariate relative risk was 0.6 (95 percent confidence interval, 0.2 to 1.3) in France but 9.3 (3.9 to 22) in the other countries . Among drugs usually used for months or years, the increased risk was confined largely to the first two months of treatment, when crude relative risks were as follows: carbamazepine, 90 (95 percent confidence interval, 19 to infinity); phenobarbital, 45 (19 to 108); phenytoin, 53 (11 to infinity); valproic acid, 25 (4.3 to infinity); oxicam nonsteroidal antiinflammatory drugs (NSAIDs), 72 (25 to 209); allopurinol, 52 (16 to 167); and corticosteroids, 54 (23 to 124) . For many drugs, including thiazide diuretics and oral hypoglycemic agents, there was no significant increase in risk . CONCLUSIONS . The use of antibacterial sulfonamides, anticonvulsant agents, oxicam NSAIDs, allopurinol, chlormezanone, and corticosteroids is associated with large increases in the risk of Stevens-Johnson syndrome or toxic epidermal necrolysis . But for none of the drugs does the excess risk exceed five cases per million users per week.

Pharmacoeconomics, 1996, 9 Suppl 1, 26 - 30
Using pharmacoeconomics to assess the comparative value of antibacterials . A UK perspective; Davey P; In the UK there is increasing pressure on prescribers to contain drug costs, the only aspect of the healthcare budget about which information is readily accessible . However, this information is often incomplete, making choices between drugs difficult . By following a defined series of steps based on identification of clinical and practical differences between 2 drugs and an evaluation of the economic consequences of these differences, prescribers can use pharmacoeconomics to make difficult decisions regarding drug choices . In doing so, prescribers can ensure that the health service spends money to provide the maximum benefit for patients.

Pharmacoeconomics, 1996, 9 Suppl 1, 1 - 8
Current principles and application of pharmacoeconomics; Malek M; Anti-infective drugs account for between 3 and 25% of all prescriptions, between 6 and 21% of the total market value of drugs in a single country, and up to 50% of the drug budget in hospitals . Not surprisingly, in an era when cost-containment policies are at the top of the agenda, issues related to pharmaco-economics of antibacterial treatment have assumed an important part in these policies . However, there are still some misunderstandings regarding the precise terminology and difference in methodology of pharmacoeconomics . The aim of this paper is to explain the genealogy of pharmacoeconomics and various methods currently used in the application of this young discipline to anti-infective treatment.

Arerugi, 1995 Dec, 44(12), 1401 - 9
{A study of clinical significance of leukocyte migration inhibition test in drug-induced hypersensitivity pneumonitis}; Uno K et al.; In 71 patients suspected of drug-induced pneumonitis, the identification of the allergenic drugs were studied by leukocyte migration inhibition test (LMIT) . The LMIT was positive in 61 cases (85.9%) . Leukocyte migration activating factor (LMAF) was detected in 22 cases (30.9%), and leukocyte migration inhibitory factor (LMIF) in 39 cases (54.9%), which was found significantly higher than LMAF (p < 0.05) . There was no considerable difference in the LMIT-positive rate between interstial and eosinophilic pneumonia . The LMIT-positive drugs were detected in 66 of all 180 suspected drugs, in which 33 drugs (50%) were antibacterial agents and 11 were Kampo prescriptions . beta-Lactam antibiotics accounted for about half the number (16 drugs) in antibacterial agents . LMAF was detected more frequently in beta-lactam antibiotics-induced pneumonitis, which LMIF was detected more often in Kampo prescriptions-induced pneumonitis (p < 0.005) . Furthermore, the latent period from drug initial to the onset of pneumonitis were about 10 days in beta-lactam antibiotics-induced pneumonitis and a few months in Kampo prescriptions-induced pneumonitis (p < 0.001) . Our findings indicate that LMIT is valuable to identify the allergenic drugs in drug-induced hypersensitivity pneumonitis and that delayed-type hypersensitivity (DTH), with which LMIF is related closely, plays a major role in the pathogenesis of this lung lesion . Furthermore, the pathogenic mechanism of beta-lactam antibiotics-induced pneumonitis may be different from that of Kampo prescriptions-induced pneumonitis.

J Pharm Biomed Anal, 1995 Dec, 14(1-2), 73 - 83
The use of capillary electrophoresis to monitor the stability of a dual-action cephalosporin in solution; Nickerson B et al.; Ro 23-9424 is a broad-spectrum antibacterial agent consisting of a cephalosporin and a quinolone moiety which are held together by an ester linkage . This compound has limited solubility in water but is more soluble at alkaline pH . Such high pH values, however, lead to stability problems due to the lability of the ester linkage, and result in the formation of the free quinolone and cephalosporin moieties . The balance between solubility and stability presents a challenge in formulation development for this compound . Thus, it is important to effectively monitor the stability of Ro 23-9424 after it has been reconstituted in different solvent systems . In this manner, a diluent which does not lead to degradation of the drug can be identified . A capillary electrophoresis method was developed and validated to monitor the stability of Ro 23-9424 . The method was found to meet acceptable criteria for method precision, system precision, linearity and limits of detection and quantitation . The method was used to monitor the stability and measure the half-life of Ro 23-9424 in water and in an L-arginine-sodium benzoate-saline diluent designed to mimic the drug delivery system . This work shows that capillary electrophoresis can be used to compare the stability of a drug in different solutions as an aid in formulation development.

Gastroenterologist, 1995 Dec, 3(4), 311 - 28
Spontaneous bacterial peritonitis: pathogenesis, diagnosis, and management; Guarner C et al.; Spontaneous bacterial peritonitis (SBP) is a common and potentially fatal complication of cirrhosis . Multiple variants of this infection have been described during the past decade; each has a slightly different clinical setting and outcome . The pathogenesis of spontaneous ascitic fluid infection appears to involve translocation of bacteria from the gut to the mesenteric lymph nodes, depressed reticuloendothelial phagocytic activity, and deficient ascitic fluid antibacterial activity . A high index of suspicion of this infection and a low threshold for performing an abdominal paracentesis are required to detect infection early, when survival is most likely . The diagnosis of SBP is based on ascitic fluid analysis, specifically polymorphonuclear cell count and culture (in blood culture bottles) . Treatment with a third-generation cephalosporin achieves a cure rate in more than 80% of patients . Despite the improvement in short-term survival during the last decade, the long-term prognosis of cirrhotic patients who survive an episode of SBP remains poor because of the severity of the underlying liver disease and the high rate of recurrence of infection . Selective intestinal decontamination to prevent SBP should be considered in patients at high risk for development of this infection, including hospitalized cirrhotic patients with gastrointestinal hemorrhage or with low ascitic fluid total protein concentration . Because SBP is a marker for poor prognosis in patients with cirrhosis, survivors of an episode of this infection should also be considered for liver transplantation.

J Nat Prod, 1995 Dec, 58(12), 1901 - 5
Metabolites of daidzein and genistein and their biological activities; Chang YC et al.; A number of metabolites of daidzein and genestein have been synthesized and their biological activities determined . Equol {3}, 5,7,4'-trihydroxyisoflavan {5}, 4,7,4'-trihydroxyisoflavan {6}, dihydrodaidzein {8}, and dihydrogenistein {9} were synthesized either from daidzein {1} or genistein {2} by hydrogenation . Similarly, the derivatives 4, 7, and 11 were synthesized from 3, 6, and 10, respectively . During acetylation and nmr experiments, 9 was converted to a novel enol intermediate {10} . Antifungal, antibacterial, mosquitocidal, nematocidal, and topoisomerase inhibition activities of these compounds were evaluated, with equol {3} being the most active of the compounds tested against topoisomerase I.

Drug Saf, 1995 Dec, 13(6), 343 - 58
Tolerability of fluoroquinolone antibiotics . Past, present and future; Ball P et al.; New fluoroquinolones have been in clinical use for 10 years and have an excellent record of safety and tolerance . The main elements of their adverse reaction profile were predictable from human experience with precursor naphthyridines and quinolones, and from toxicological studies in animals . Thus gastrointestinal reactions (1 to 5%), skin disturbances (less than 2.5%) and central nervous system (CNS) effects (usually around 1 to 2%) were anticipated . Individual group members exhibit particular properties in relation to their chemical structures, for example the phototoxicity associated with 8-halogenation of the nucleus and found to be a particular problem with lomefloxacin and sparfloxacin . Other members, for example ofloxacin, are linked to a higher than usual incidence of CNS reactions and psychological disturbance . However, despite increasing usage, none of the present group have been implicated in joint damage in children, which had been a major concern following reports of this effect in juvenile animals in chronic toxicity studies . Furthermore, intravenous formulations appear to have no associated increase in toxicity . Crystalluria with associated renal damage, originally thought likely to limit intravenous dosage, has not proved to be a problem in humans . Clinically significant interactions may occur but, as with those involving various NSAIDs and potentially leading to convulsions, they have been defined and are thus avoidable . Postmarketing surveillance studies and prescription event monitoring have largely confirmed the limited adverse reaction profile defined during clinical trials . However, some unexpected reactions have appeared after launch, most notably the episodes of haemolysis, renal failure and hypoglycaemia which led to the withdrawal of temafloxacin . These effects have not been observed with other fluoroquinolones . However, severe tendinitis appears to be a group effect, albeit rare, and anaphylactoid reactions have been reported with several of the fluoroquinolone group, often in AIDS patients . The new fluoroquinolones are essentially a well tolerated group of antibacterials, the benefits of which clearly outweigh their disadvantages in a wide range of indications . Clinical efficacy has been a larger determinant of which members have succeeded in the marketplace than potential toxicity . However, the lesser potential for adverse effects of some of the class, e.g . norfloxacin, ofloxacin and ciprofloxacin, has undoubtedly led to their more widespread use . For others, e.g . enoxacin, limited clinical utility and a perception of increased toxicity have resulted in sidelining . There remains the potential for development of safer and yet more active fluoroquinolones via chemical manipulation both of the nucleus and the side chain substituents.

J Endod, 1995 Dec, 21(12), 592 - 3
Clinical evaluation of the efficacy of EDTA solution as an endodontic irrigant; Yoshida T et al.; The effect of eliminating the smear layer by means of 15% EDTA solution as a root canal irrigant was studied in 189 single-rooted infected teeth . Each tooth was treated at two appointments, and the root canal bacteriological examination was studied on the first (pretreatment, and after enlargement and irrigation) and second (pretreatment) visits . The root canals were irrigated with 15% EDTA solution with ultrasonics agitation . No antibacterial intracanal medications were used between the appointment . When 15% EDTA solution was used, no bacteria could be recovered from 93 of 129 root canals at the sampling stage on second visit . No bacteria were found in 21 of 60 root canals when saline solution was used as an irrigant . These results suggest that 15% EDTA solution is more effective than saline solution as a root canal irrigant.

Antimicrob Agents Chemother, 1995 Dec, 39(12), 2752 - 8
Antibacterial action of ciprofloxacin; Mason DJ et al.; The mechanisms by which quinolones rapidly kill are ill defined . We have investigated the action of ciprofloxacin on Escherichia coli KL16 with a combination of traditional and flow cytometric methods and have analyzed cells for changes in membrane potential, membrane integrity, oxidative metabolism, morphology, and viability . Log-phase cultures were exposed to various concentrations (0.1, 1, 10, and 100 times the MIC) of ciprofloxacin and analyzed at regular intervals over 120 min . We also measured protein synthesis in the related strain PQ37 cultured under the same conditions over 300 min, using a colorimetric assay for beta-galactosidase release . Despite a 3-log order decrease in CFU after 60-min exposure to 10 and 100 times the MIC of ciprofloxacin, there was no equivalent decrease in bacterial numbers as determined by both light microscopy and flow cytometry . Furthermore, while these bacteria showed concentration-dependent morphological changes, most were capable not only of excluding the fluorescent nucleic acid-binding dye propidium iodide, but also of reducing the tetrazolium dye cyanoditodyl tetrazolium chloride . Over 90% of the bacteria maintained a membrane potential {as determined by exclusion of bis-{1,3-dibutylbarbituric acid) trimethine oxonol} when exposed to ciprofloxacin for 120 min, except at 100 times the MIC, when this figure fell to < 10% . Finally, protein synthesis was either maintained or induced at all concentrations of ciprofloxacin up to 5 h postexposure . Taken together, these results demonstrate the continuing physical and metabolic survival of ciprofloxacin-exposed bacteria; we suggest parallels with the concept of the viable nonculturable state.

Antimicrob Agents Chemother, 1995 Dec, 39(12), 2620 - 4
Can penicillins and other beta-lactam antibiotics be used to treat tuberculosis?
Chambers HF, Moreau D, Yajko D, Miick C, Wagner C, Hackbarth C, Kocagoz S, Rosenberg E, Hadley WK, Nikaido H.
An increase in the number of tuberculosis cases caused by multiple-drug-resistant strains of Mycobacterium tuberculosis has stimulated search for new antituberculous agents . Beta-lactam antibiotics, traditionally regarded as ineffective against tuberculosis, merit consideration . Four major penicillin-binding proteins (PBPs) with approximate molecular sizes of 94, 82, 52, and 37 kDa were detected by fluorography of {3H}penicillin-radiolabeled membrane proteins prepared from M . tuberculosis H37Ra . The presence of membrane-associated beta-lactamase precluded the use of membranes for assaying the binding affinities of beta-lactam antibiotics . Therefore, ampicillin affinity chromatography was used to purify these four PBPs from crude membranes in order to assay the binding affinities of beta-lactam antibiotics . Ampicillin, amoxicillin, and imipenem, beta-lactam antibiotics previously reported to be active in vitro against M . tuberculosis, bound to M . tuberculosis PBPs at therapeutically achievable concentrations . Binding of the 94-, 82-, and 52-kDa PBPs, but not the 37-kDa PBP, was associated with antibacterial activity, suggesting that these PBPs are the critical targets . Studies of mycobacterial cell wall permeability, which was assayed with a panel of reference cephalosporins and penicillins with different charge positivities, indicated that the rate of penetration of beta-lactam antibiotics to the target PBPs could not account for resistance . Resistance could be reversed with the beta-lactamase inhibitors clavulanate or sulbactam or could be circumvented by the use of a beta-lactamase-stable drug, imipenem, indicating that mycobacterial beta-lactamase, probably in conjunction with slow penetration, is a major determinant of M . tuberculosis resistance to beta-lactam antibiotics . These findings confirm in vitro data that M . tuberculosis is susceptible to some beta-lactam antibiotics . Further evaluation of these drugs for the treatment of tuberculosis in animal models and in clinical trials is warranted.

Phytochemistry, 1995 Dec, 40(6), 1691 - 5
Antibacterial triterpenoids from Dillenia papuana and their structure-activity relationships; Nick A et al.; Two new oleanene-type triterpenoids, dillenic acids D and E, have been isolated from the leaves and stems of Dillenia papuana together with the new natural product 3-oxoolean-12-en-30-oic acid . Together with these compounds, the known compound, betulinic acid (3 beta-hydroxy-20(29)-lupen-28-oic acid) was isolated as the major component of the fractions studied . Dillenic acids D and E were characterized as 2,3-seco-2-oxoolean-12-en-3-methylester-30-oic acid and 1 alpha,3 beta-dihydroxyolean-12-en-30-oic acid and their nuclear magnetic resonance data were unambiguously assigned using two-dimensional nuclear magnetic resonance techniques . A comparison of antibacterial activities of these compounds with the earlier reported dillenic acids A-C indicated that, aside from a double bond in gamma- or delta-position to a carboxylic group, a ketone function in ring A of an oleanene-skeleton may be required for the observed activity.

Jpn J Antibiot, 1995 Dec, 48(12), 1891 - 8
In vitro antibacterial activity of FA103, a new quinolone derivative of C-7 position with 7-perhydrodiazepinone; Imamori K et al.; A number of new quinolone antibacterial agents such as ofloxacin, norfloxacin, ciprofloxacin and sparfloxacin have been developed and introduced to the market . They possess a broad spectrum of activity against Gram-positive and Gram-negative bacteria . Ciprofloxacin has the highest activity against Gram-positive is higher than other quinolones . The activity of these quinolones against Gram-negative bacteria is generally higher than against Gram-positive bacteria . The substitution group of quinolones at C-7 position is responsible to show similar antibacterial activity with broad spectrum and similar pharmacokinetic properties, and variety of the substituents have been synthesized in many laboratories . Most of the substituents are piperazinyl of six-membered ring or pyrrolidinyl of five-membered ring, being modified with an alkyl group or another group . The development of potent quinolones against bacteria involved in pneumonia was seemed to be useful, and we investigated structure-activity relationships of new quinolones with a stronger activity against Gram-positive bacteria . A quinolone derivative with a seven-membered ring, perhydrodiazepinone, at the C-7 position was found to be a candidate for further evaluation . No previous attempts have been made to synthesize this type of derivatives . The compound FA103, 5-amino-1-cyclopropyl-6,8-difluoro-7-(2,3,4,5,6,7-hexahydro-1 H-1,4-diazepin-5-on-1-yl)-1,4-dihydro-4-oxoquinoline-3-carboxylic acid, was synthesized and evaluated . Chemical structure of FA103 is shown in Fig . 1 . This is a new difluoroquinolone with a broad antibacterial spectrum and improved activity against Gram-positive bacteria . In this paper, we compare the in vitro activity of FA103 with that of ofloxacin, norfloxacin, sparfloxacin against Gram-positive and Gram-negative bacteria.

Chem Pharm Bull (Tokyo), 1995 Dec, 43(12), 2246 - 52
Synthesis of possible metabolites of 1-cyclopropyl-1,4-dihydro-6-fluoro-5-methyl-7-(3-methyl-1-piperazinyl)- 4-oxo-3-quinolinecarboxylic acid (Grepafloxacin, OPC-17116); Morita S et al.; Grepafloxacin (1-cyclopropyl-1,4-dihydro-6-fluoro-5-methyl-7-(3-methyl-1-piperazinyl )-4-oxo-3-quinoline-carboxylic acid, OPC-17116) (1) exhibits potent and broad-spectrum in vitro and in vivo antibacterial activity . In order to identify the structures of the metabolites of grepafloxacin, 17 possible metabolites were prepared . Among them, 6 compounds were found to be actual metabolites (2a, b, 4a, b and 6a, b) of grepafloxacin in rats, dogs and/or humans . The antibacterial activities of these metabolites were found to be weaker than that of grepafloxacin.

Chem Pharm Bull (Tokyo), 1995 Dec, 43(12), 2123 - 32
Imidazo- and triazoloquinolones as antibacterial agents . Synthesis and structure-activity relationships; Fujita M et al.; 4,5-Disubstituted 6-cyclopropyl-6,9-dihydro-9-oxo-1H-imidazo (30-32) and triazolo{4,5-f}quinoline-8-carboxylic acids (33-35) were synthesized starting from 5,6-diaminoquinolones 25 . The imidazoquinolones 30-32 were equal or superior to the corresponding triazoloquinolone analogues 33-35 in in vitro antibacterial activity . As for the C-5 substituents, a fluorine atom was the most favorable of the three groups, H, F, and Cl . Among the compounds prepared, 4-(cyclic amino)-5-fluoro-imidazoquinolones 31 a-d showed potent and well-balanced antibacterial activity against both gram-positive and gram-negative bacteria . Structure-activity relationships for the C-4 substituents (cyclic amino groups) were also examined in detail.

J Antibiot (Tokyo), 1995 Dec, 48(12), 1481 - 7
Synthesis and antibacterial activity of 2-(isoxazolidinio-5-yl)carbapenem derivatives; Nishi K et al.; The synthesis and antibacterial activity of the title compounds having an isoxazolidine ring at the C-2 position are described . These derivatives were synthesized by the 1,3-dipolar cycloaddition reaction of nitrone with 2-vinyl carbapenems . This 1,3-dipolar cycloaddition reaction proceeded regioselectively to give diastereomeric isomers of 2(-isoxazolidin-5-yl)carbapenems . It was ascertained that the antibacterial activity of 1 beta-methylcarbapenem derivatives was superior to that of the corresponding 1H-carbapenem derivatives, and between the 2-(isoxazolidin-5-yl)-1 beta-methylcarbapenems the antibacterial activity of the 5'R-isomer was slightly better than that of the 5' R-isomer slightly better than that of the 5' S-isomer.

J Laryngol Otol, 1995 Dec, 109(12), 1197 - 9
Stridor in patients with HIV infection; Laing RB et al.; The immunodeficiency which results from HIV infection is associated with a range of opportunistic infections and tumors which may present with the symptoms of upper airways disease . This paper presents three cases of stridor from different causes in patients with HIV infection, all of whom recovered following treatment . The management of this problem requires consideration of the likely aetiology which, in those with advanced immunodeficiency, includes bacterial and fungal laryngitis and epiglottitis as well as rapidly growing laryngeal tumours . Recommendations for the treatment of those with HIV infection who present with severe or rapid-onset stridor should include a combination of aggressive airway intervention and broad-spectrum antibacterial and antifungal agents . Laryngeal biopsy for histology and culture is particularly important for those patients who fail to respond to the aforementioned treatment.

Biochem J, 1995 Nov 15, 312 ( Pt 1), 107 - 14
Glycosylated and unglycosylated human lactoferrins both bind iron and show identical affinities towards human lysozyme and bacterial lipopolysaccharide, but differ in their susceptibilities towards tryptic proteolysis; van Berkel PH et al.; We studied the role of N-glycosylation of human lactoferrin (hLF) with respect to properties that are relevant to its antibacterial and anti-inflammatory activities . A human kidney-derived 293(S) cell line that constitutively expresses recombinant hLF (rhLF) was produced . The reactivity towards various antibodies of rhLF that had been expressed in the absence or presence of tunicamycin (which blocks N-linked glycosylation) did not differ from that of natural (human milk-derived) hLF . Cation-exchange chromatography and N-terminal protein sequencing showed identical cationic properties and an intact N-terminal sequence for rhLF and natural hLF . SDS/PAGE of rhLF expressed in the presence of tunicamycin revealed a protein with the same M(r) as that of enzymically deglycosylated natural hLF . Both glycosylated and unglycosylated rhLF appeared to be completely saturated with iron . The affinity of natural hLF, glycosylated and non-glycosylated rhLF for both human lysozyme (Kd 4.5 x 10(-8) M) and bacterial lipopolysaccharide did not differ . SDS/PAGE of hLF species subjected to trypsin indicated that unglycosylated rhLF was much more susceptible to degradation . Furthermore, this analysis suggests that N-glycosylation heterogeneity in natural hLF and rhLF resides in the C-lobe . Thus our results provide no argument for differential antibacterial and/or anti-inflammatory activity of natural and (glycosylated) rhLF and suggest that a major function of glycosylation in hLF is to protect it against proteolysis.

Antibiot Khimioter, 1995 Nov-Dec, 40(11-12), 40 - 4
{Resistance of Pseudomonas mallei to tetracyclines: assessment of the feasibility of chemotherapy}; Manzeniuk IN et al.; The spectrum of cross resistance in tetracycline resistant strains of Pseudomonas mallei was studied . Possible use of antibacterial drugs in the prevention and treatment of mallel due to such strains was investigated in the experiments on golden hamsters and monkeys . It was shown that the efficacy of the minocycline therapy depended on the level of the strain resistance to tetracycline antibiotics . The combination of biseptol and ofloxacin proved to be highly efficient in the treatment of mallei.

Gen Pharmacol, 1995 Nov, 26(7), 1539 - 43
Screening for antibacterial agents in three species of sea cucumbers from coastal areas of Sabah; Ridzwan BH et al.; 1 . Three species of sea cucumbers found in the Sabah coastal areas were screened for the presence of antibacterial activity using three methods of extraction . Tests were conducted in vitro using the agar absorption method . 2 . Both the lipid extract and the methanol-solvent extract from Holothuria atra, Holothuria scabra and Bohadshia argus were found to show no antibacterial activity . 3 . Phosphate-buffered saline (PBS) from H . atra and B . argus, however, inhibited the growth of all gram-positive and gram-negative bacteria . 4 . Comparisons were also made between extracts from the outer layer of H . atra and its inner part, and it was found that the extract from the outer layer showed less bacterial growth inhibition property . 5 . The bacterial growth inhibition property of the PBS extract from H . atra, however, is dependent on the extract's concentration . Bacterial growth inhibition was apparent after 48 hr incubation.

Inflamm Res, 1995 Nov, 44(11), 461 - 5
Flush induced by fluoroquinolones in canine skin; Kurata M et al.; The flush induced by two fluoroquinolone antibacterial agents, balofloxacin and ofloxacin, was studied in beagle dogs . Intradermal injection of the fluoroquinolones at concentrations above 10(-5) M produced a localized flushed area . The flush responses to fluoroquinolones were inhibited by co-administration with H2-antagonist(s) (ranitidine or cimetidine), but not with H1-antagonist(s) (mepyramine or chlorpheniramine) . Similar inhibitory effects of these H2-antagonists were observed for the response to histamine . The flush responses to fluoroquinolones were inhibited by a local pretreatment with compound 48/80 administered to deplete the local stores of mast cell-bound histamine . When the fluoroquinolones were orally administered at a dose of 400 mg/kg, the concentration of histamine in plasma was increased, being accompanied by systemic erythema . These results indicate that the flush induced by fluoroquinolones is mediated by histamine release from canine cutaneous mast cells and H2-receptor stimulation.

J Nat Prod, 1995 Nov, 58(11), 1730 - 4
Isolation and characterization of cytotoxic and antibacterial tetrasaccharide glycosides from Ipomoea stans; Reynolds WF et al.; Three new tetrasaccharide glycosides, differing from one reported previously in the type of short-chain fatty acids ester-linked to the tetrasaccharide core, have been isolated and identified from an oligosaccharide fraction of Ipomea stans . Preliminary screening tests showed that the fraction containing these compounds had pronounced cytotoxicity towards three human tumor cell lines as well as specific antibiotic activity against two bacterial strains.

Clin Infect Dis, 1995 Nov, 21(5), 1303 - 5
Seroepidemiology of Helicobacter pylori infection in heart transplant recipients; Dummer JS et al.; We analyzed serum samples obtained from 100 heart transplant recipients before and after transplantation for the presence of IgG antibodies to Helicobacter pylori . Enzyme-linked immunosorbent assay revealed that 35 patients were seropositive before the procedure . Seropositive patients were older than seronegative patients, but the two groups did not differ in terms of cardiac diagnosis, gender, survival, or the number of admissions or rejection episodes . In addition, seropositive patients did not have more-frequent episodes of gastritis, ulcer disease, or gastrointestinal bleeding . Over a mean serological follow-up of 3.4 years, only one of 65 seronegative patients seroconverted . Of the 35 seropositive patients, 14 became seronegative for H . pylori a median of 194 days (range, 47-2,657 days) after transplantation . Seroreverters, as compared with serofast patients, had received more intravenous and total antibiotics during follow-up (P = .01), were more likely to have received a combination of antibiotics active against H . pylori (P < .025), and had received more antirejection treatment (P = .01) . The incidence of H . pylori infection is not increased after heart transplantation, and many seropositive patients serorevert after transplantation when antibacterial and immunosuppressive agents are administered.

J Small Anim Pract, 1995 Nov, 36(11), 481 - 8
Feline asthma syndrome: a retrospective study of the clinical presentation in 29 cats; Corcoran BM et al.; Feline asthma syndrome (FAS) is a clinical condition characterised by recurrent bouts of coughing, wheezing and, or, dyspnoea . While the aetiology is unproven, the condition is believed to involve a type I immediate hypersensitivity reaction to inhaled allergens . In this paper the clinical data from 29 cats, where a diagnosis of FAS was made, are assessed retrospectively . The most common clinical presentation was recurrent bouts of coughing (n = 26) and dyspnoea (n = 21) . Radiographic changes were noted in 24 cats, which included increased bronchial (n = 5), interstitial (n = 7) and mixed (n = 12) (bronchial and interstitial) patterns . Right middle lung lobe collapse was noted in two cats . Abnormal bronchial cytology was present in 16 cats . A predominant eosinophilic sample was collected in only three cats . There were minimal changes in differential white cell counts, and mild eosinophilia was found in only five cats . Prednisolone alone was the most effective therapy, although avoidance of putative aeroallergens and antibacterial therapy was effective in some . On the basis of the data from these cases it would appear that the diagnosis of FAS depends largely on the clinical presentation and radiographic findings . The value of ancillary tests in the diagnosis of FAS appears to be limited.

Eur J Cancer, 1995 Nov, 31A(12), 2013 - 22
An approach to the design and implementation of clinical trials of empirical antibiotic therapy in febrile and neutropenic cancer patients; Viscoli C et al.; The results of many clinical trials on empirical therapy in febrile, neutropenic cancer patients cannot be readily transferred to the clinical practice, because the methodology is often flawed and definitions, study endpoints and eligibility criteria differ from trial to trial . This article critically reviews some issues related to the design and implementation of randomised clinical trials of empirical antibiotic therapy in cancer patients . Within the definition of phase III clinical trials, two approaches co-exist, based on the trial's specific aims: the "explanatory" approach and the "pragmatic" approach . The usual "explicit" aim of clinical trials of empirical therapy in febrile, neutropenic patients has been that of comparing the "efficacy" of two regimens . However, this term has been more often used with reference to the antibacterial activity of the regimen under study (explanatory aim) than to indicate the practical benefits it draws to the overall patient population treated for fever and neutropenia (pragmatic aim) . These two meanings are often taken as perfectly interchangeable, while, conversely, they are completely distinct (though not independent) treatment effects . Most trials conducted in this patient population in recent years are explanatory trials, though not explicitly so, but their results have been widely applied to clinical practice, as they were pragmatic trials . In an explanatory trial the appropriate endpoint is success or failure (defined by clinical and laboratory data) among those patients affected with the specific infection for which the study drug is being given, while in pragmatic trials survival is probably the more appropriate outcome variable, since they are designed to assess the practical benefits that the overall population of febrile and neutropenic patients can obtain from the new empirical treatment . Unfortunately, survival is not a practical study endpoint for the difficulty in assessing the cause of death in this patient population and, especially, for the need for very large sample sizes, which might render the implementation problematic even for large, multicentre groups . Both types of trials need an intention to treat analysis, but this is especially crucial for pragmatic trials, which should not differentiate those cases in which success was obtained through multiple treatment modifications from those who did not require any treatment change . Obviously, this implies that no conclusion should be drawn about the antibacterial activity of the study drugs and that the number of treatment modifications should be taken into account in the interpretation of the results, especially for quality of life and cost evaluations . Information related to fever and signs of infection, age, underlying disease, neutropenia and concomitant administration of other antibiotics are crucial entry criteria that need to be clearly discussed and defined . Finally, the evaluation of toxicity is problematic in this patient population, due to the existence of a number of toxigenic factors, including the underlying disease, the type of infectious complication, the administration of chemotherapy and radiotherapy and the use of parental nutrition . All these effects tend to overlap, thus impairing the investigator's ability to detect specific drug-related side-effects.

J Antibiot (Tokyo), 1995 Nov, 48(11), 1336 - 44
The chemistry of pseudomonic acid . Part 14 . Synthesis and in vivo biological activity of heterocyclyl substituted oxazole derivatives; Broom NJ et al.; Semisynthetic analogues of pseudomonic acid A have been prepared containing a heterocyclyl substituted oxazole . Derivatives in which the heterocycle was thiophene, furan, pyridine, or isoxazole showed good antibacterial potency and were further evaluated in vivo . Both pharmacokinetic parameters and oral activity against an experimental intraperitoneal sepsis were superior to results obtained from previously described pseudomonic acid A derivatives.

J Antibiot (Tokyo), 1995 Nov, 48(11), 1248 - 53
Trichorzins HA and MA, antibiotic peptides from Trichoderma harzianum . I . Fermentation, isolation and biological properties; Goulard C et al.; Trichorzins HA and MA, original 18-residue peptides, were isolated from two strains of the widespread soil fungus Trichoderma harzianum which have been shown to exhibit antibiotic activity against phytopathogenic fungi . These linear peptides belonging to the peptaibol class are biosynthesized as a complex of closely related analogues . Nine major pure peptides, six trichorzins HA and three trichorzins MA, were isolated by reversed-phase HPLC . The isolated peptides exhibited antibacterial activity against S . aureus and increased the membrane permeability of egg phosphatidylcholine/cholesterol (7/3) liposomes, as measured by monitoring leakage kinetics of a fluorescent probe . Structure-activity relationships were deduced from the antibiotic and membrane-modifying properties.

J Clin Periodontol, 1995 Nov, 22(11), 860 - 7
Response to intracrevicular controlled delivery of 25% tetracycline from poly(lactide/glycolide) film strips in SPT patients; Maze GI et al.; Controlled local delivery of antibiotics has been shown to reduce periodontopathic micro-organisms with minimal side-effects . Clinical studies in our laboratory have shown that 25% tetracycline HCl delivered from poly(D,L-lactide/glycolide) film strips (25 TTC-PLGA) released therapeutic concentrations of tetracycline for 10 days . The present pilot study compared the intracrevicular delivery of 25% tetracycline HCl incorporated in these biodegradable film strips to scaling and root planing (SRP) in 10 adult periodontitis patients, who in spite of therapy and regular supportive periodontal treatment (SPT), continued to possess 5 bleeding periodontal pockets at least 5 mm deep . Sites were randomly selected to receive the following treatments: (1) 25 TTC-PLGA, (2) control strips without TTC (PLGA), (3) SRP, and (4) untreated control . Film-strip retention was augmented with a suture/cement technique, followed by strip removal after 2 weeks . Clinical parameters and subgingival bacterial morphotypes (darkfield analysis) were evaluated over time (0, 2.4, 8, 12, 26 weeks) . Results indicated that, compared to baseline, 25 TTC-PLGA film strips caused significant (p < or = 0.01): (1) probing depth reduction for 26 weeks, (2) a clinical attachment level gain for 12 weeks, (3) lower %s of spirochetes for 4 weeks and motile rods for 8 weeks (p < or = 0.05), and (4) an accompanying increase in cocci for 4 weeks . In the scaled and root planed sites, probing depth was the only finding that demonstrated a significant change from baseline (p < or = 0.01) . Controls and PLGA showed isolated reductions in probing depth and % of motile organisms . From these findings, applications of intracrevicular 25 TTC-PLGA, when compared to scaling and root planing, appears to have an enhanced antibacterial effect and a similar clinical effect in SPT patients . The results of this study indicate further investigation of 25 TTC-PLGA film strips should be undertaken using more subjects and sophisticated microbiological and clinical measurements.

Br J Rheumatol, 1995 Nov, 34 Suppl 2, 7 - 15
Sulphasalazine: mechanism of action in rheumatoid arthritis; Smedegard G et al.; Sulphasalazine a drug used for the treatment of rheumatoid arthritis (RA) shows a wide range of biological activities all of which might contribute to the beneficial clinical effect seen during treatment of RA . This review summarizes some of the biological activities and discusses these in context of possible modes of action of the drug . Sulphasalazine has been described as an antibacterial drug, an anti-inflammatory drug or as an immunomodulator . From the reviewed data it is concluded that the effects of sulphasalazine on various immunological processes, are of outstanding importance for its mode of action.

J Bacteriol, 1995 Nov, 177(21), 6153 - 9
Topology analysis of the colicin V export protein CvaA in Escherichia coli; Skvirsky RC et al.; The antibacterial protein toxin colicin V is secreted from Escherichia coli cells by a dedicated export system that is a member of the multicomponent ATP-binding cassette (ABC) transporter family . At least three proteins, CvaA, CvaB, and TolC, are required for secretion via this signal sequence-independent pathway . In this study, the subcellular location and transmembrane organization of membrane fusion protein CvaA were investigated . First, a series of CvaA-alkaline phosphatase (AP) protein fusions was constructed . Inner and outer membrane fractionations of cells bearing these fusions indicated that CvaA is inner membrane associated . To localize the fusion junctions, the relative activities of the fusion proteins, i.e., the amounts of phosphatase activity normalized to the rate of synthesis of each protein, as well as the stability of each fusion, were determined . These results indicated that all of the fusion junctions occur on the same side of the inner membrane . In addition, the relative activities were compared with that of native AP, and the protease accessibility of the AP moieties in spheroplasts and whole cells was analyzed . The results of these experiments suggested that the fusion junctions occur within periplasmic regions of CvA . We conclude that CvaA is an inner membrane protein with a single transmembrane domain near its N terminus; the large C-terminal region extends into the periplasm . This study demonstrates the application of AP fusion analysis to elucidate the topology of a membrane-associated protein having only a single transmembrane domain.

Arch Surg, 1995 Nov, 130(11), 1234 - 40; discussion 1240-1
Clinical significance of antibiotic endotoxin-releasing properties in trauma patients; Mock CN et al.; OBJECTIVE: To test the hypothesis that antibiotics leading to greater endotoxin release are associated with greater mortality in septic trauma patients . DESIGN: Post hoc analysis of data from a previously conducted prospective, randomized, multicenter study designed to evaluate the efficacy of interferon gamma in preventing infection and death in trauma patients . SETTING: Nine level I trauma centers . PATIENTS: Severely injured trauma patients at high risk for sepsis . Eighty percent (N = 334) of the enrolled patients developed some manifestation of gram-negative sepsis, defined by the administration of gram-negative specific antibiotics . MAIN OUTCOME MEASURES: The in-hospital mortality rate of patients who received penicillin-binding protein 3/tumor necrosis factor (PBP3/TNF)-specific antibiotics associated with the greatest degree of endotoxin release and TNF production (PBP3/TNF group, n = 78: aztreonam, ceftazidime, and cefotaxime sodium) was compared with that of patients not receiving these agents (non-PBP3/TNF group, n = 256) . RESULTS: Mortality in the PBP3/TNF group (17%) was higher than in the non-PBP3/TNF group (8%, P = .02) . The two groups were similar in their mean (+/- SD) Injury Severity Scores (34 +/- 9), ages (31 +/- 12 years), and initial degree of bacterial contamination . CONCLUSIONS: Antibiotics that are associated with greater release of endotoxin and production of TNF are also associated with greater mortality in septic trauma patients . Decisions regarding antibiotic administration may need to consider the endotoxin-releasing properties of antibiotics in addition to their antibacterial sensitivity spectrum . Prospective studies of the effect of endotoxin-releasing properties of antibiotics on mortality are warranted.

Plast Reconstr Surg, 1995 Nov, 96(6), 1317 - 25
The effect of Biocell texturing and povidone-iodine irrigation on capsular contracture around saline-inflatable breast implants; Burkhardt BR et al.; We performed a prospective, concurrently controlled, and blinded 4-year clinical study on 60 patient volunteers to determine the effects of two independent variables, McGhan's Biocell texturization and Betadine antibacterial irrigation, on the incidence of fibrous capsular contracture around saline-inflatable implants following retromammary augmentation . Each patient was randomly assigned both a textured and a smooth implant and both saline and Betadine irrigation so that each patient served as her own control . The textured devices irrigated with Betadine experienced an overall incidence of contracture of only 4 percent compared with 50 percent for the smooth devices irrigated with saline solution . The Betadine-irrigated devices in general had a lower incidence of contracture than the saline-irrigated devices, and the textured-surface devices in general had a lower incidence of contracture than the smooth devices . Antibacterial irrigation and surface texturization may work in a cumulative manner to reduce the early incidence of capsular contracture.

J Chromatogr B Biomed Appl, 1995 Oct 20, 672(2), 225 - 31
Extraction of the synthetic lytic peptide, cecropin B, from biological fluid and analysis using reversed-phase high-performance liquid chromatography; Moore AJ et al.; The lytic peptide cecropin B, originally isolated from the giant silk moth Hyalophora cecropia, has been found to possess antibacterial and cell lysis properties in vitro and some anticancer activity in vivo . An HPLC method was developed to study synthetic cecropin B concentrations in biological fluids . Cecropin B was recovered from culture medium by solid-phase extraction (40.0 +/- 2.4%), whereas in plasma it was highly protein-bound . The peptide was dissociated from proteins by citric acid and recovered by ultrafiltration (64.6 +/- 5.9%) and was unstable in plasma (half-life, 0.57 +/- 0.11 h) . These analytical methods will facilitate future in vivo pharmacokinetic studies.

J Med Chem, 1995 Oct 13, 38(21), 4244 - 56
2-Substituted penems with amino acid-related side chains: synthesis and antibacterial activity of a new series of beta-lactam antibiotics; Altamura M et al.; A new series of 6-(hydroxyethyl)penems 2-substituted with amino acid-related side chains was synthesized . The nature of the amino acyl derivative proved to be crucial both from a synthetic point of view, as beta-lactam ring opening can compete with C-2 nucleophilic substitution, and for antibacterial activity . Primary amino acid amides emerged as the most suitable side chains for enhancing permeability through a Gram-negative outer membrane . In vitro activity of the new 2-{(aminoamido)methyl}penems 3a-u was influenced by the nature and position of the amide moiety, the ring size for cyclic amides, and the configuration of the amino acid . Compounds bearing amides derived from small N-methyl amino acids (such as 3a) or from cyclic amino acids (such as prolinamide 3p and 4-hydroxyprolinamide 3r) showed broad spectrum in vitro activity against both Gram-positive and Gram-negative microorganisms.

Proc Natl Acad Sci U S A, 1995 Oct 10, 92(21), 9465 - 9
A recessive mutation, immune deficiency (imd), defines two distinct control pathways in the Drosophila host defense; Lemaitre B et al.; In this paper we report a recessive mutation, immune deficiency (imd), that impairs the inducibility of all genes encoding antibacterial peptides during the immune response of Drosophila . When challenged with bacteria, flies carrying this mutation show a lower survival rate than wild-type flies . We also report that, in contrast to the antibacterial peptides, the antifungal peptide drosomycin remains inducible in a homozygous imd mutant background . These results point to the existence of two different pathways leading to the expression of two types of target genes, encoding either the antibacterial peptides or the antifungal peptide drosomycin.

Gene, 1995 Oct 3, 163(2), 215 - 9
Structure of two cecropin B-encoding genes and bacteria-inducible DNA-binding proteins which bind to the 5'-upstream regulatory region in the silkworm, Bombyx mori; Taniai K et al.; Two genomic DNAs encoding cecropin B (CecB), an antibacterial protein from Bombyx mori, were cloned and sequenced . The number of CecB genes was estimated to be more than four copies per haploid by genomic Southern blotting . Two genes, CecB1 and CecB2, were located tandemly within 12 kb in the same orientation . These two genes encoded identical amino acids, though 15 nucleotides (nt) were different in the coding region and the intron size varied . About 90% of the nt spanning 800 bp in the 5'-untranslated region (UTR) were identical between the two genes . This 5'-flanking region contained characteristic sequences such as a repetitive element of B . mori (Bm1), an interleukin-6 response element (IL-6 RE), and two putative lipopolysaccharide (LPS) response elements (LPS RE) . An electrophoretic mobility shift assay (EMSA) showed that the fat body contains at least three different nuclear proteins inducible by bacteria which bind to the 5'-UTR, suggesting that these proteins may be involved in CecB expression triggered by bacteria.

Biochemistry, 1995 Oct 3, 34(39), 12729 - 37
Structure of the 70-kDa soluble lytic transglycosylase complexed with bulgecin A . Implications for the enzymatic mechanism; Thunnissen AM et al.; Bulgecins are O-sulfonated glycopeptides that are able to enhance the antibacterial activity of beta-lactam antibiotics . The 70-kDa soluble lytic transglycosylase (SLT70) from Escherichia coli forms a specific target of these compounds . Using X-ray crystallography, the three-dimensional structure of a complex of SLT70 with bulgecin A has been determined to 2.8-A resolution and refined to an R factor of 19.5% . The model contains all 618 amino acids of SLT70 and a single molecule of bound bulgecin, located in the active site of the enzyme . The glycopeptide inhibitor is bound in an extended conformation occupying sites analogous to the B, C, and D subsites of lysozyme . Upon binding of bulgecin, the three-stranded antiparallel beta-sheet in the C domain shows a pronounced shift toward the inhibitor . In subsite D, the proposed catalytic residue Glu478 forms a hydrogen bond to the hydroxymethyl oxygen of the proline part of bulgecin and interacts electrostatically with the proline NH2+ group . These interactions, in addition to the interactions observed for the 2-acetamido group of the N-acetylglucosamine residue bound in subsite C, may explain the strong inhibition of SLT70 activity by bulgecin, suggesting that bulgecin acts as an analogue of an oxocarbonium ion intermediate in the reaction catalyzed by SLT70 . The structure of the SLT70--bulgecin A complex may be of assistance in the rational design of novel antibiotics.

Singapore Med J, 1995 Oct, 36(5), 484 - 6
Evaluation of the efficacy of sequential intravenous-oral administration of pefloxacin in community-acquired lower respiratory tract infections in patients with underlying conditions; Yap JC et al.; We studied the efficacy of sequential intravenous-oral pefloxacin therapy in community-acquired lower respiratory tract infection in 24 patients with one or more underlying conditions . Twenty-eight patients were enrolled into the study but only 24 patients were evaluated . There were 16 males and 8 females with a mean age of 66.9 +/- 11.2 years (mean +/- SD, range 46 to 87 years) . The underlying conditions present were bronchiectasis, chronic obstructive lung disease and diabetes mellitus . Patients who were older than 70 years but without any underlying condition were also enrolled . All received 4 days of intravenous pefloxacin 400 mg twice a day followed by oral pefloxacin 400 mg twice a day for another 10 days . Assessment of success was based on clinical, microbiological and radiological improvement . Pefloxacin produced 79.2% clinical cure rate . Another 8.3% showed improvement . Pefloxacin was well tolerated . There were few adverse effects and none of the patients required a change of antibiotic . Pefloxacin was an effective and well tolerated treatment for respiratory tract infection and had the advantage of broad in-vitro antibacterial activity, twice daily dosing and sequential availability in an intravenous and oral formulation.

Ann Pharmacother, 1995 Oct, 29(10), 994 - 6
Rifampin-fluconazole interaction in critically ill patients; Nicolau DP et al.; OBJECTIVE: To report the influence of rifampin coadministration on the pharmacokinetics of fluconazole in 2 critically ill patients . CASE SUMMARIES: The pharmacokinetics of fluconazole are reported in 5 patients in the intensive care unit (ICU), 2 of whom received rifampin and 3 who received only fluconazole . Patient 1 was a 52 year-old man with bilateral pneumonia who received rifampin for 9 days in addition to other antibiotics when fluconazole was added for suspected fungal superinfection . Patient 2, a 39-year-old man with steroid-dependent asthma was admitted to the ICU with a right middle lobe pneumonia and ventilatory insufficiency . Because of rapid clinical deterioration, intravenous rifampin 600 mg q12h and fluconazole 100 mg q24h were added to conventional antibacterial therapy . Patients 3-5 received intravenous fluconazole therapy, but were never administered rifampin prior to their antifungal therapy . DISCUSSION: Fluconazole has gained wide use as an antifungal agent because of its efficacy, limited toxicity, and the paucity of reported drug interactions . In some clinical situations, however, the drug must be coadministered with rifampin . Limited data in healthy volunteers suggest that the coadministration of rifampin and fluconazole results in a 23% reduction in the fluconazole area under the concentration-time curve (AUC) . In this report, we found a statistically significant lowering of the AUC (52%) and a 93% higher total body clearance of fluconazole in patients treated with rifampin . CONCLUSIONS: Although limited data are available describing the magnitude of the interaction between fluconazole and rifampin in patients, our data suggest a more significant interaction than previously reported . If the concurrent administration of the 2 drugs in unavoidable, the patient's clinical response to treatment should be monitored closely, as the unexpectedly large reduction in fluconazole serum concentrations may lead to poor treatment outcomes.

J Clin Periodontol, 1995 Oct, 22(10), 750 - 5
The effect of oxidising mouthrinses compared with chlorhexidine on salivary bacterial counts and plaque regrowth; Moran J et al.; For various clinical indications, oxidising agents have been used in dentistry for many years . Little is known, however, of their antibacterial activity and their ability to inhibit plaque formation . In this study, 2 mouthrinses containing peroxyborate (Bocasan) and peroxycarbonate (Kavosan) were compared alongside a negative control saline rinse and a positive control chlorhexidine rinse (Corsodyl) for their ability to inhibit plaque reformation . Employing a randomised four replicate 4 x 4 latin square cross over design and, whilst omitting all other oral hygiene, plaque was measured by area and index after rinsing for 4 days . In a second study, in vivo antibacterial effects of the rinses were assessed by measuring salivary bacterial counts following single rinses with the preparations at various time intervals over 7 h . Plaque inhibition by chlorhexidine was significantly greater than the other rinses . All rinses were significantly better than the saline rinse at inhibiting plaque . For plaque area, the peroxycarbonate rinse was significantly better than the peroxyborate rinse at inhibiting plaque . Salivary bacterial count reductions were significantly greater compared to saline with chlorhexidine at all time intervals up to 7 h . Whilst both peroxyborate and peroxycarbonate rinses produced greater reductions in bacterial counts than saline up to 3 h, at no time interval were the differences significant . The findings of these studies would suggest oxidising mouthrinses may inhibit plaque formation not by a direct antibacterial effect, but by some other mechanism . The magnitude of plaque reductions obtained with the peroxyborate and more so peroxycarbonate rinses would suggest a need for further study of these preparations when used as adjuncts to normal toothbrushing.

Clin Infect Dis, 1995 Oct, 21(4), 881 - 6
Candida-associated diarrhea: a syndrome in search of credibility; Levine J et al.; Candida species have been often considered but infrequently documented as a credible cause of diarrhea . Evaluations of the colon in patients who have diarrhea and for whom Candida organisms have been isolated from stool have not shown invasive fungal lesions, and the mechanisms by which Candida species may induce diarrhea remain undefined . However, symptoms ascribed to Candida-associated diarrhea in the literature include prolonged secretory diarrhea with abdominal pain and cramping but without blood, mucus, fever, nausea, or vomiting . A critical review literature review showed a strong between the abatement of diarrheal symptoms in patients for whom a significant growth of Candida was found in their stools and treatment with specific topical antifungal agents . Most of the patients had received antibacterial therapy before the onset of symptoms . On the basis of these data, we conclude that Candida species may cause diarrhea in selective clinical settings.

Arzneimittelforschung, 1995 Oct, 45(10), 1131 - 2
Synthesis and antibacterial activity of substituted 4-arylaminopyrimido{5,4-c}cinnolines; Nargund LV et al.; A series of 4-arylamino pyrimido{5,4-c}cinnolines was synthesized and evaluated for antibacterial activity by serial 2-fold dilution technique . Several compounds showed significant activity . Amongst them 7-methyl-4-{(p-methyl phenyl) amino} pyrimido {5,4-c} cinnoline (2f) was the most active against Gram positive bacteria.

Chem Pharm Bull (Tokyo), 1995 Oct, 43(10), 1678 - 82
Synthesis and antibacterial activities of optically active substituted 1,2-dihydro-6-oxo-6H-pyrrolo{3,2,1-ij}quinoline-5-carboxylic acids; Tsuji K et al.; A series of optically active substituted 1,2-dihydro-6-oxo-pyrrolo{3,2,1-ij}quinoline-5-carboxylic acids was prepared via optically active 2-methyl-4,5-difluoroindoline (10) and tested for antibacterial activities . Among them, (2S)-9-{(3R,1'S)-3-(1'-amino)ethyl-1-pyrrolidinyl}-8-fluoro-1,2-dihydro- 2- methyl-6-oxo-6H-pyrrolo{3,2,1-ij}-quinoline-5-carboxylic acid (19) showed potent activity against gram-positive bacteria and (2S)-8-fluoro-1,2-dihydro-2-methyl-9-(3-methyl-1-piperazinyl)-6-oxo-6H- pyrrolo{3,2,1-ij}quinoline-5-carboxylic acid (16) exhibited well balanced in vitro activity, good intravenous efficacy, and high aqueous solubility.

Biosci Biotechnol Biochem, 1995 Oct, 59(10), 1842 - 5
Enhancement of production of IgM and interferon-beta in human cell lines by poly-lysine; Yamamoto MM et al.; The promotive effects of poly-cations on immunoglobulin production was investigated using human-human hybridoma cells . Among poly-cations tested, epsilon-poly-L-lysine with hydrochloride (approximately 4 kDa), which has been used as an antibacterial food additive, had the greatest activity in enhancing IgM production of human-human hybridoma HB4C5 cells without stimulating cell proliferation . Immunoglobulin production stimulatory (IPS) activity of epsilon-poly-lysine was not affected by trypsin digestion . It was stable below 60 degrees C but completely inactivated with heating at 100 degrees C for 30 min . epsilon-Poly-lysine also enhanced interferon-beta (IFN-beta) production of human osteosarcoma MG-63 cells, but this stimulatory effect was reduced by the trypsin digestion.

Int J Pancreatol, 1995 Oct, 18(2), 81 - 94
Development and regulation of porcine pancreatic function; Pierzynowski SG et al.; A surgical and experimental procedure was developed to enable the collection of pure and inactivated pancreatic juice during the growth of the pig . Studies have shown that, during the suckling period, both the basal and the secretory responses to suckling are low, if present at all . After weaning, basal levels of the total exocrine secretion, total protein, amylase, and trypsin, respectively, increase slightly, while the postprandial levels of total protein, amylase, trypsin, lipase, colipase, and carboxylester lipase, respectively, increase markedly . The pancreatic juice enzyme composition changes qualitatively and the antibacterial activity of the pancreatic juice also significantly increases . Piglet age appeared to be of minor importance, since weaning at either 4 or 6 wk of age gave the same results . Secretin and CCK administered together in supraphysiological doses only significantly affect exocrine function from 3-4 wk of age . However, CCK may also affect the exocrine pancreas indirectly via reflexes initiated intraduodenally . Milk consumption in the suckling pig leads to a postprandial increase in glucose levels but not insulin . Milk appears to be able to regulate the exocrine pancreas to produce only the amount and type of enzymes required for digestion . Thus, milk components or digestive products may affect pancreas function regulation . Studies show that enterostatin, the procolipase activation peptide, may inhibit pancreatic secretion mediated indirectly through the GI tract . Pancreastatin, an endocrine peptide, inhibits both insulin secretion and protein and trypsin secretion to pancreatic juice . In hypoinsulinemic (alloxan+streptozotocin diabetes) pigs (15-20 kg), no postprandial pancreatic juice response is seen, although CCK 33 + secretin can stimulate pancreatic secretion . Hypoinsulinemic pigs have a reduced capacity for glucose tissue utilization, suggesting that tissue metabolism and exocrine pancreas secretion are related.

BMJ, 1995 Sep 30, 311(7009), 862 - 3
Harnessing the strengths of the leprosy programme to control tuberculosis; Lockwood DN et al.; Tuberculosis remains a leading cause of death in Ethiopia but there is no effective national tuberculosis control programme . By contrast, the leprosy control programme has been very successful, with a 10-fold reduction in the number of leprosy cases requiring antibacterial treatment, though patients with nerve damage require continuing care . The paradox of rising numbers of tuberculosis cases and declining numbers of leprosy cases may be solved by joint leprosy-tuberculosis clinics . The strengths of leprosy fieldworkers in control management, case holding, and compliance can be harnessed in developing an effective tuberculosis control programme . Implementing a joint programme in Ethiopia may be beneficial not only for tuberculosis patients but also for leprosy patients, who are thus brought closer to general medical services.

Biochemistry, 1995 Sep 12, 34(36), 11479 - 88
Interaction of the mammalian antibacterial peptide cecropin P1 with phospholipid vesicles; Gazit E et al.; Cecropins are positively charged antibacterial polypeptides that were originally isolated from insects . Later on a mammalian homologue, cecropin P1 (CecP), was isolated from pig intestines . While insect cecropins are highly potent against both Gram-negative and Gram-positive bacteria, CecP is as active as insect cecropins against Gram-negative but has reduced activity against Gram-positive bacteria . To gain insight into the mechanism of action of CecP and the molecular basis of its antibacterial specificity, the peptide and its proline incorporated analogue (at the conserved position found in insect cecropins), P22-CecP, were synthesized and labeled on their N-terminal amino-acids with fluorescent probes, without significantly affecting their antibacterial activities . Fluorescence studies indicated that the N-terminal of CecP is located on the surface of phospholipid membranes . Binding experiments revealed that CecP binds acidic phosphatidylserine/phosphatidylcholine (PS/PC) vesicles better than zwitterionic PC vesicles, which correlates with its ability to permeate the former better than the latter . The shape of the binding isotherms suggest that CecP, like insect cecropin, binds phospholipids in a simple, noncooperative manner . However, resonance energy transfer (RET) measurements revealed that, unlike insect cecropins, CecP does not aggregate in the membrane even at relatively high peptide to lipid ratios . The stoichiometry of CecP binding to vesicles suggests that amount of CecP sufficient to form a monolayer causes vesicle permeation . In spite of the incorporation of the conserved proline in P22-CecP, the analogue has reduced antibacterial activity, which correlates with its reduced alpha-helical structure and its lower partitioning and membrane permeating activity with phospholipid vesicles . Taken together, our results support a mechanism in which CecP disrupts the structure of the bacterial membrane by (i) binding of peptide monomers to the acidic surface of the bacterial membrane and (ii) disintegrating the bacterial membrane by disrupting the lipid packing in the bilayers . These results, combined with data reported for other antibacterial polypeptides, suggest that the organization of peptide monomers within phospholipid membranes contributes to Gram-positive/Gram-negative antibacterial specificity.

Tidsskr Nor Laegeforen, 1995 Sep 10, 115(21), 2663 - 8
{Resistance development of major pathogenic bacteria}; Kristiansen BE et al.; In recent years the emergence of strains of drug-resistant bacteria has become a major health problem in many parts of the world . This has made it vitally necessary both to develop new antibacterial drugs and establish effective strategies to combat invading bacteria . In Norway, drug-resistant bacteria are a minor problem as yet, but the situation could change quite quickly if the necessary precautions are not taken . These include not prescribing antibacterial drugs too freely, and thoroughly surveying the extent of drug-resistance in an attempt to confine and prevent infection with resistant bacteria.

Biochem Biophys Res Commun, 1995 Sep 5, 214(1), 271 - 8
cDNA cloning and gene expression of lebocin, a novel member of antibacterial peptides from the silkworm, Bombyx mori; Chowdhury S et al.; A cDNA encoding lebocin, a novel member of insect antibacterial peptides, was isolated from the fat body cDNA library of Bombyx mori larvae immunized with Escherichia coli . The cDNA was 844 bp long and had an open reading frame (ORF) containing a probable signal peptide (16 amino acids), a putative prosegment (104 amino acids) and a mature peptide (32 amino acids) followed by 27 additional amino acids at its carboxyl-terminus . Northern blot analysis showed that lebocin gene expression was inducible by bacterial injection, occurred tissue-specifically in the fat bodies and continued at least for 48 h post-infection . These results suggest that lebocin has a unique precursor structure and shows typical gene expression pattern as insect antibacterial peptide.

Dev Comp Immunol, 1995 Sep-Oct, 19(5), 357 - 63
Parallel induction of cecropin and lysozyme in larvae of the silkworm, Bombyx mori; Morishima I et al.; Lysozyme activity in the hemolymph of Bombyx mori increased in parallel with cecropin activity after injection of the larvae with soluble peptidoglycan or UV-killed bacteria . The lysozyme and cecropin A genes were expressed in parallel in the fat body after injection of peptidoglycan as detected by northern blot hybridization . The elicitor specificity for lysozyme induction was identical to that for cecropin, suggesting a common mechanism for recognition of bacteria and following signal transduction introducing to the simultaneous synthesis of cecropin and lysozyme . Bacterial cells killed by UV-irradiation were also effective as elicitor when added to the fat body culture, suggesting that phagocytosis of bacteria by hemocytes may not be an essential process for the induction of antibacterial protein synthesis in the silkworm.

Hua Xi Yi Ke Da Xue Xue Bao, 1995 Sep, 26(3), 261 - 5
{Antibacterial components of rat uterus}; Xu L et al.; The acid-soluble extract of rat uterus cavity wall was obtained by washing out the normal Sprague-Dawley rat uterus cavity with 1% acetic acid in the presence of protease inhibitors . When tested for antibacterial activity by sensitive agarose diffusion assay, the extract effectively killed E . coli ML-35P . The bactericidal activity of the acid-soluble extract was further analyzed by gel overlay technique . The result showed that three protein bands, which were designated rat uterus protein 1 (rat UP-1), rat uterus protein 2 (rat UP-2), and rat uterus protein 3 (rat UP-3), were potently antibacterial against E . coli ML-35P . The rat UP-1, rat UP-2, and rat UP-3 accounted for 4.5%, 5.7%, and 6.6% of the total proteins of the rat uterus acid-soluble extract respectively . The lysoplate assay for the determination of lysozyme activity showed that extract had some lysozyme activity, but the activity was very low . AU-PAGE analysis of the extract did not show the presence of lysozyme on the gel . This study suggested that the uterus wall might secrete some currently-unknown antibiotic polypeptides which play an important role in the uterus defense against bacterial infections.

Mikrobiol Z, 1995 Sep-Oct, 57(5), 78 - 83
{Microbiological studies of stomatological periodontal films containing a derivative of chlorocinnamic aldehyde}; Davtian LL et al.; Stomatological parodontal films removing the effect of negative factors on the parodontal have been studied . Antibacterial effect of the derivative of chlorocinnamic aldehyde, composition ingredients and their different combinations as well as the films as a whole have been studied when creating stomatological parodontal films.

Infection, 1995 Sep-Oct, 23(5), 316 - 21
Comparative pharmacodynamics of clarithromycin and azithromycin against respiratory pathogens; Bauernfeind A et al.; The differences between the antibacterial activities of new macrolides such as clarithromycin (CLA) and azithromycin (AZI) against common respiratory tract pathogens are only minor . However, CLA and AZI constitute macrolides with extremely different pharmacokinetic profiles . This constellation presents an opportunity to evaluate the effect of the pharmacokinetic profile on antibacterial kinetics comparatively . In a pharmacodynamic model simulating the dynamics of serum concentrations in bacterial cultures, both CLA and AZI demonstrate bactericidal activity at concentrations reached in human blood at recommended dosages (CLA 250 mg b.i.d., AZI 500 mg o.i.d.) . Bactericidal activity of CLA against the variety of pathogens included is superior to that of AZI in the rate and the extent of killing in this model . These results are considered to correlate with the antibacterial effect of macrolides in vivo in cases where pathogens enter the blood stream . Furthermore, mutants with susceptibility reduced between 8 and 16 times in relation to the initial strain of all strains having an initial minimal inhibitory concentration (MIC) < or = 0.25 mg/l, are selected during exposure to AZI, but not to CLA . The pharmacokinetic profiles of CLA and AZI thus strongly influence their antibacterial effect in the pharmacodynamic model, allowing both higher bactericidal activity and greater reduction of the risk of selection of resistant mutants with CLA than with AZI . As a whole, the pharmacodynamics of these macrolides are determined more by the proportion of the MICs to the maximum serum concentration than by the relation of the MICs to the area under the curve.

Infection, 1995 Sep-Oct, 23(5), 298 - 300
Synergy of simultaneous administration of ofloxacin and granulocyte colony-stimulating factor in killing of Escherichia coli by human neutrophils; Kropec A et al.; The in vitro effect of subinhibitory and inhibitory concentrations of ofloxacin and G-CSF on the bactericidal activity of polymorphonuclear leucocytes (PMNL) against Escherichia coli was investigated . PMNL obtained from healthy volunteers were incubated with different concentrations of G-CSF and ofloxacin for 180 min . The minimum inhibitory concentration (MIC) of ofloxacin and even 1/4 x MIC enhanced the bactericidal activity of PMNL . G-CSF at a concentration of 6,000 units/ml led to a significant improvement of the bactericidal activity of PMNL . The combination of 6,000 units/ml of G-CSF and ofloxacin in inhibitory as well as subinhibitory concentrations, however, showed a significant synergistic effect on the antibacterial activity of PMNL during the complete incubation period . Combinations of G-CSF and antibiotics could therefore be beneficial for infected patients, especially those with impaired cellular host defense.

Antimicrob Agents Chemother, 1995 Sep, 39(9), 2104 - 11
Formulation and efficacy of liposome-encapsulated antibiotics for therapy of intracellular Mycobacterium avium infection; Oh YK et al.; Mycobacterium avium is an intracellular pathogen that can invade and multiply within macrophages of the reticuloendothelial system . Current therapy is not highly effective . Particulate drug carriers that are targeted to the reticuloendothelial system may provide a means to deliver antibiotics more efficiently to M . avium-infected cells . We investigated the formulation of the antibiotics ciprofloxacin and azithromycin in liposomes and tested their antibacterial activities in vitro against M . avium residing within J774, a murine macrophage-like cell line . A conventional passive-entrapment method yielded an encapsulation efficiency of 9% for ciprofloxacin and because of aggregation mediated by the cationic drug, was useful only with liposomes containing < or = 50 mol% negatively charged phospholipid . In contrast, ciprofloxacin was encapsulated with > 90% efficiency, regardless of the content of negatively charged lipids, by a remote-loading technique that utilized both pH and potential gradients to drive drug into preformed liposomes . Both the cellular accumulation and the antimycobacterial activity of ciprofloxacin increased in proportion to the liposome negative charge; the maximal enhancement of potency was 43-fold in liposomes of distearoylphosphatidylglycerol-cholesterol (DSPG-Chol) (10:5) . Azithromycin liposomes were prepared as a freeze-dried preparation to avoid chemical instability during storage, and drug could be incorporated at 33 mol% (with respect to phospholipid) . Azithromycin also showed enhanced antimycobacterial effect in liposomes, and the potency increased in parallel to the moles percent of negatively charged lipids; azithromycin in DSPG-Chol (10:5) liposomes inhibited intracellular M . avium growth 41-fold more effectively than did free azithromycin . Thus, ciprofloxacin or azithromycin encapsulated in stable liposomes having substantial negative surface charge is superior to nonencapsulated drug in inhibition of M.avium growth within cultured macrophages and may provide more effective therapy of M.avium infections.

Antimicrob Agents Chemother, 1995 Sep, 39(9), 1979 - 83
Effect of levofloxacin on glycosaminoglycan and DNA synthesis of cultured rabbit chondrocytes at concentrations inducing cartilage lesions in vivo; Kato M et al.; We investigated the toxic effect of levofloxacin (LVFX), a quinolone antibacterial agent, on cartilage by examining aspects of its in vivo toxicokinetics and effect on the function of cultured chondrocytes of the femoral articular cartilage from juvenile New Zealand White rabbits . Repeated administration of LVFX (100 mg/kg) orally for 7 days induced focal necrosis and superficial erosion in the articular cartilage of the femoral condyle, but 30 mg/kg did not . Concentrations of LVFX in the cartilage were highest at the first sampling point (30 min) after a single administration, being 4.93 and 12.2 micrograms/g in the 30- and 100-mg/kg groups, respectively . The arthropathic concentration of LVFX in the cartilage was then shown to be 12.2 micrograms/g or more . For an in vitro study, chondrocytes were separated from the articular cartilage of the rabbit femoral condyle and cultured for 7 days until confluence . 35SO4 uptake by cultured chondrocyte sheets was most susceptible to LVFX, decreasing at drug concentrations of 5 micrograms/ml or more in 24- and 48-h cultures but not in a 72-h culture . Furthermore, 3H-thymidine uptake was decreased at concentrations of 10 micrograms/ml or more in a 48-h culture but not in 24- and 72-h cultures . Rhodamine 123 accumulation was susceptible to inhibition in cultured chondrocytes at an LVFX concentration of 10 micrograms/ml or more . These results suggest that LVFX inhibits glycosaminoglycan synthesis initially and DNA synthesis and mitochondrial function secondarily at actual arthropathic concentrations in cultured rabbit chondrocytes but that these changes are reversible and not enough to kill the cells.

J Pharm Sci, 1995 Sep, 84(9), 1061 - 6
Transdermal delivery of dideoxynucleoside-type anti-HIV drugs . 1 . Stability studies for hairless rat skin permeation; Kim DD et al.; The stability of dideoxynucleoside-type anti-HIV drugs in solution when in contact with hairless rat skin was investigated in order to study the feasibility of their transdermal delivery . The freshly excised dorsal region of hairless rat skin was mounted on Valia-Chien skin permeation cells, and both epidermis (donor) and dermis (receptor) were extracted with isotonic phosphate buffer (pH 7.4) at 37 degrees C for 24 h . Zalcitabine (DDC), didanosine (DDI), and zidovudine (AZT) were found to be stable in the extract of the epidermis at 37 degrees C for at least 30 h . However, DDC and DDI degraded in the extract of the dermis following first-order kinetics at both 25 and 37 degrees C, while AZT was stable at 37 degrees C for at least 30 h . The degradation mechanism(s) of DDC and DDI was (were) studied by analyzing HPLC chromatograms and by evaluating the drug stability in the extract which was filtered to remove any microbes . An unidentified peak produced by DDC in the dermis extract did not appear when the drug was added to the filtered extract, which suggested a bacterial degradation of DDC . On the other hand, DDI was unstable even in the filtered extract and produced a degradation product which corresponded to hypoxanthine, which suggested that a cutaneous enzyme is also involved in the degradation of DDI . DDC was stabilized by the addition of 0.01% (w/v) of an antibacterial agent, such as thimerosal or gentamicin, in the receptor solution, while DDI was stabilized by 0.01% (w/v) purine nucleoside phosphorylase inhibitor, i.e., p-chloromercuribenzoic acid . These results show the importance of stability studies when designing skin permeation experiments using hairless rat since compounds with similar chemical structures can have different stability profiles when in contact with hairless rat skin.

Pediatr Dent, 1995 Sep-Oct, 17(5), 351 - 5
In vitro inhibition of bacteria from root canals of primary teeth by various dental materials; Tchaou WS et al.; The primary tooth pulpectomy is a common clinical procedure . The choice of filling material is important to the success rate, but antibacterial properties of such materials against organisms known to inhabit infected primary root canals have not been well documented . This study compared the antibacterial effectiveness of 10 materials: 1 . Calcium hydroxide mixed with camphorated parachlorophenol (Ca(OH)2+CPC) 2 . Calcium hydroxide mixed with sterile water (Ca(OH)2+H2O) 3 . Zinc oxide mixed with CPC (ZnO+CPC) 4 . Zinc oxide mixed with eugenol (ZOE) 5 . ZOE mixed with formocresol (ZOE+FC) 6 . Zinc oxide mixed with sterile water (ZnO+H2O) 7 . ZOE mixed with chlorhexidine dihydrochloride (ZOE+CHX) 8 . Kri paste 9 . Vitapex paste 10 . Vaseline (control) These materials were compared against microbial specimens obtained from 13 infected primary teeth by using an agar diffusion assay . The results suggest that the materials could be divided into three categories . Category I, with the strongest antibacterial effect included ZnO+CPC, Ca(OH)2+CPC, and ZOE+FC . Category II, with a medium antibacterial effect included ZOE+CHX, Kri, ZOE, and ZnO+H2O . Category III, with no or minimal antibacterial effect included Vitapex, Ca(OH)2+H2O, and Vaseline . There were no significant differences within each category, but there were significant differences between the categories . The one exception was the antibacterial effect of ZOE+FC which was not significantly different from ZOE+CHX, Kri, or ZOE.

Fogorv Sz, 1995 Sep, 88(9), 293 - 7
{Excretion of fluoroquinolones into saliva}; Kelentey BA et al.; The excretion of three fluoroquinolones derivatives into the saliva were studied in animal experiments . Ofloxacin per os administered to rabbits was excreted into the saliva well, and maintained the therapeutic level long--about 7 hours . Pefloxacin and ciprofloxacin iv . administered to mice were similarly excreted into the saliva at therapeutic levels and retained the antibacterial level for about 4 hours.

Biochem J, 1995 Sep 1, 310 ( Pt 2), 651 - 6
A novel antibacterial peptide family isolated from the silkworm, Bombyx mori; Hara S et al.; Three structurally related and novel antibacterial peptides have been isolated from the haemolymph of the silkworm, Bombyx mori, immunized with Escherichia coli . These peptides were 32 amino acids long and characteristically rich in proline residues . A unique threonine residue in each peptide was O-glycosylated and the modification seemed to be important for expression of antibacterial activity . The primary structure and antibacterial character of the novel peptides resemble those of abaecin (41% identity in amino acid sequence), an antibacterial peptide of the honeybee, although abaecin is not O-glycosylated . Incubation of the novel peptides with a liposome preparation caused leakage of entrapped glucose under low-ionic-strength conditions, suggesting that a target of the peptides is the bacterial membrane . We propose the name 'lebocin' for the novel peptide family isolated from B . mori.

J Antibiot (Tokyo), 1995 Sep, 48(9), 977 - 89
Chrysospermins, new peptaibol antibiotics from Apiocrea chrysosperma Ap101; Dornberger K et al.; Four new members of peptaibol antibiotics, designated as chrysospermins A, B, C, and D, were isolated from the mycelium of Apiocrea chrysosperma Ap101 by solvent extraction, silica gel chromatography and preparative recycling HPLC . Their structures as new nonadecapeptides were settled by detailed spectroscopic analysis and chemical degradation experiments . The chrysospermins display antibacterial and antifungal activity, and induce pigment formation by the fungus Phoma destructiva.

Drug Ther Bull, 1995 Sep, 33(9), 71 - 2
In-vitro activity of antibacterial drugs and clinical practice; Synthesis and biological activity of novel metal complexes of 2-acetylpyridine thiosemicarbazones; Department of Chemistry, University of Calabar, Nigeria2-Acetylpyridine-(2-methylthiosemicarbazone), 2-acetylpyridine-(4-methylthiosemicarbazone), 2-acetylpyridine-(4-phenylthiosemicarbazone) and some of their metal complexes of the platinum group have been synthesized, characterized by chemical and spectral methods and studied for their antibacterial, antifungal and amoebicidal activity in vitro . They were studied also for their antimalarial activity and for toxicity in vivo . The platinum metal chelates exhibited significant activity against a wide spectrum of microorganisms at different concentrations . The Ru (III) chelates derived from 2-acetylpyridine-(4-methylthiosemicarbazone) seem to be the most efficient inhibitors . Evaluation of the antimalarial activity of the complexes in mice infected with Plasmodium berghei indicated that cures were attainable at dose levels of 20-160 mg/kg.

J Nat Prod, 1995 Sep, 58(9), 1467 - 9
Anguillosporal, a new antibacterial and antifungal metabolite from the freshwater fungus Anguillospora longissima; Harrigan GG et al.; Anguillosporal {1}, a new antifungal and antibacterial metabolite, has been isolated from the freshwater fungus Anguillospora longissima (CS-869-1A) . Its structure was determined as 2,4-dihydroxy-3-ethyl-6-(1'-methylpentyl)-benzaldehyde on the basis of ms, 1H-nmr, and 13C-nmr data.

Infect Dis Clin North Am, 1995 Sep, 9(3), 769 - 81
Adjuncts to antibacterial therapy; Frank MO et al.; Strategies of augmenting or attenuating the immune system's response to infection are promising potential methods to enhance antibacterial therapy . Many of these new therapies are natural cytokines, such as the hematopoietic growth factors and interferons, which upregulate the immune response . Other examples include replacement therapies, such as immune globulin, and downregulators of the immune response, such as corticosteroids . In the near future it may be possible to adjust the host response to microbial infection to maximally inhibit the microbe while minimizing inflammatory damage.

Infect Dis Clin North Am, 1995 Sep, 9(3), 561 - 74
Antibacterial agents in pediatrics; LiPuma JJ et al.; The utility of various antibacterial agents for therapy of infectious diseases in children is determined by the unique pharmacokinetics and potential toxicity in children . The important age-related principle of pharmacokinetics is reviewed in the first section of this article; the second section focuses on specific therapeutic agents and their use in children . Particular emphasis is given to the use of new antibiotics in children, including the new oral cephalosporins and macrolides.

Infect Dis Clin North Am, 1995 Sep, 9(3), 531 - 45
Principles of selection and use of antibacterial agents; Hessen MT et al.; Treatment of infection involves a complex interaction among the infecting organism (susceptibility to the therapeutic agent), host factors (immune function, site of infection, renal and hepatic metabolism), and pharmacokinetics (rate of absorption, distribution and excretion) . Successful therapy requires careful consideration of these factors, and unsuccessful treatment should invoke a careful reanalysis of them.

Antibiot Khimioter, 1995 Aug, 40(8), 40 - 2
{Microflora of purulent necrotic leisions of the foot in patients with diabetes mellitus}; Svetukhin AM et al.; Microflora of purulent necrotic lesions of the foot in 14 patients with diabetes mellitus was investigated by aerobic and anaerobic procedures . It was shown that the process was due to the same species of pathogenic microorganisms irrespective of the lesion severity . However, the number of the pathogens in the associations and the dissemination level per a patient were higher when the lesions were extended . The tissue microbial dissemination in the purulent foci was also higher in the patients with wounds complicated by marked inflammation of the surrounding tissues and the tissues under the lesion . The time course of the changes in the foot microflora during the target-aimed antibacterial therapy was followed up.

Antibiot Khimioter, 1995 Aug, 40(8), 36 - 9
{Evaluation of the effectiveness of the use of pefloxacin in combined radiation-thermal injury}; Makarov GF et al.; The efficacy of pefloxacin, a novel promising antibacterial drug of the group of fluoroquinolones, was studied on mice against doxycycline in the prevention and treatment of infectious complications of radiation/thermal injury . According to the data on the effect of the antibiotics on the resistance to exogenic infection and the development of dysbacteriosis pefloxacin was recommended for the use in the scheme of combined therapy of radiation/thermal injury.

J Vet Pharmacol Ther, 1995 Aug, 18(4), 274 - 83
Design of field trials for the evaluation of antibacterial products for therapy of bovine clinical mastitis; Schukken YH et al.; In this paper, the design and statistical analysis of field trials for the evaluation of the efficacy of clinical mastitis therapeutics is covered . First, general issues underlying the design of clinical trials are reviewed . These include bias and confounding; randomization and blocking; and study objectives and choice of the corresponding hypothesis . Specific issues in the design of clinical mastitis trials are also discussed . Selection of subjects is discussed with regard to choice of experimental units, identification of reference population and study population, inclusion and exclusion criteria, and sample size calculation . Next, a section on treatment administration and evaluation of cure reviews treatment, blinding, choice of response measure, as well as compliance, withdrawal, and early termination . The statistical analysis section addresses possible statistical models, treatment of confounding, and fixed vs . random effects . In conclusion, well-conducted clinical mastitis trials represent an invaluable, albeit difficult and expensive, effort to evaluate efficacy and tolerance under usual circumstances of use.

J Chemother, 1995 Aug, 7(4), 338 - 43
Once-daily dosing regimen for aminoglycoside plus betalactam combination therapy of serious lower respiratory tract infections; Paradisi F et al.; Aminoglycosides are important antibacterial agents for treatment of serious gram-negative bacillary infections including lower respiratory tract infection . Once-daily aminoglycosides result in higher peak and lower trough plasma concentrations than conventional multiple daily dosing regimens; once-daily aminoglycoside therapy is equally effective, generally less toxic and much less expensive and therefore this regimen is more and more frequently used for treatment of suspected or confirmed gram-negative bacillary infections and of febrile episodes in neutropenic patients, in particular in combination with an appropriate betalactam antibiotic . Despite the lack of studies on this topic, once-daily aminoglycosides in combination with a betalactam agent can be used in subjects with lower respiratory tract infection, including patients with cystic fibrosis, in which tobramycin appears to be the aminoglycoside antibiotic of choice.

J Chemother, 1995 Aug, 7(4), 286 - 91
Evaluation of the invasive techniques for diagnosing bacterial respiratory infections; Pozzi E et al.; Bacterial community-acquired respiratory infections are usually sustained by strains highly responsive to antibiotic therapy . Thus, the clinical approach is based on an empirical treatment and does not require the isolation of the causative pathogen and the determination of the bacterial susceptibility to antibiotics . On the other hand, Gram-negative bacteria, most commonly multidrug resistant, frequently affect immunocompromised and nosocomial patients and their identification in cultures is absolutely necessary for proper antibacterial treatment . To this aim, two conventional methods are used, i.e . the blood culture, which is positive only in 20% of pneumonia cases, and the sputum culture, which is not invasive but easily contaminated by oropharyngeal flora . Consequently, invasive techniques for sampling the pathologic specimen, such as the BAL and the PSB, performed with the help of fiberoptic bronchoscope, are needed . The diagnostic power and the limits of both these techniques are analyzed . Moreover, the opportunity to obtain quantitative cultures, which may discriminate between contamination and infection is considered.

Clin Infect Dis, 1995 Aug, 21(2), 323 - 7
Meningitis caused by Candida species: an emerging problem in neurosurgical patients; Nguyen MH et al.; Three cases of candida meningitis were encountered in a 3-year period in our hospital; all occurred in neurosurgical patients . We describe these three cases and review the 15 cases of neurosurgery-related candida meningitis previously reported in the English-language literature . Data regarding these 18 patients formed the basis for our review . Most patients with candida meningitis had recently received antibacterial agents, and it is notable that 50% of patients suffered from antecedent bacterial meningitis . The CSF analysis revealed neutrophilic pleocytosis that was indistinguishable from that of bacterial meningitis . The overall mortality was 11% . Administration of amphotericin B combined with flucytosine appeared to be the best therapeutic approach for candida meningitis.

Am J Kidney Dis, 1995 Aug, 26(2), 381 - 4
Apophysomyces elegans infection in a renal transplant recipient; Naguib MT et al.; A 50-year-old cadaveric renal transplant recipient on immunosuppressive therapy is described with post-traumatic cutaneous infection caused by Apophysomyces elegans . He showed no evidence of hematogenous dissemination and recovered fully after therapy with extensive local debridement and amphotericin B lipid complex . An apparent drug-drug interaction between amphotericin B lipid complex and cyclosporine was encountered . The course of A elegans infection in transplant recipients may be similar to that described in immunocompetent hosts . A elegans infection should be considered in evaluation of post-traumatic cutaneous infection not readily responsive to antibacterial therapy.

Infect Immun, 1995 Aug, 63(8), 3062 - 8
Increased translocation of Escherichia coli and development of arthritis in vitamin A-deficient rats; Wiedermann U et al.; We studied the immune response and the colonization pattern in vitamin A-deficient rats that were colonized with the Escherichia coli O6 K13 pOmp 21 strain, which is genetically manipulated to produce ovalbumin and to be resistant to ampicillin . In the vitamin A-deficient rats, the number of bacteria per gram of feces was about five times higher than in the paired fed control rats 4 weeks after colonization . In the control rats, the colon and the lower part of the ileum were colonized, while in the vitamin A-deficient rats all parts of the small intestine, as well as the colon, were heavily inhabited by bacteria . Furthermore, in 75% of the vitamin A-deficient rats, the E . coli bacteria were found in the mesenteric lymph nodes, and in 50% of the rats E . coli were found in the kidneys . These animals also developed severe arthritis . The levels of serum immunoglobulin G (IgG), IgM, IgE, and biliary IgA antibodies against the bacterial antigens were significantly higher in the vitamin A-deficient rats than in the control rats . The number of IgA-producing cells in the lamina propria of the small intestine was significantly lower in the vitamin A-deficient rats than in the control rats; however, there was an increase in the number of CD8+ cells and transforming growth factor beta-producing cells in the lamina propria of the vitamin A-deficient rats . Disturbances in T-cell function were demonstrated, since spleen cells from the vitamin A-deficient rats produced more gamma interferon and interleukin-2 in vitro than control spleen cells . In summary, vitamin A deficiency led to a decrease in the ability to control the localization of intestinal bacteria and an increase in translocation, which was followed by development of arthritis regardless of substantial levels of antibacterial antibodies . The bacterial invasion made the animals hyperresponsive to the bacterial antigens, despite the fact that vitamin A deficiency is normally associated with suppressed antibody production, as previously shown by us and others.

J Cell Biochem, 1995 Aug, 58(4), 481 - 9
Light and electron microscopic immunocytochemical localization of two major proteins in garlic bulb; Wen GY et al.; Garlic is known as a potent spice and a medicine with broad therapeutic properties ranging from antibacterial to anticancer, antidiabetic, and anticoagulant . Two major proteins of 40 KD and 14 KD constituting approximately 96% of total garlic proteins have been recently purified at our Institute . This immunocytochemical and ultrastructural study revealed that the 40 KD protein was localized in the parenchyma sheath cells (PSC) of garlic bulbs, whereas the 14 KD protein was present in the cortical cells (CC) . Immunogold electron microscopy study indicated that the 40 KD protein was specifically localized in the globular granules of the cytoplasmic area of PSC . Each globular granule was amorphous and homogenous with membrane limiting its outermost layer . The yellowish color of PSC in freshly cut slices of garlic bulb suggested that PSC may have sulfur-containing compounds such as allicin, the primary contributor of the pungency and medicinal properties of garlic . Ellman's reagent test quantitatively revealed that there were 17.8 n moles sulfhydryl (SH)/ml of 40 KD garlic protein . Microtubule tubulin in mitotic figures from PHA-stimulated human short-term whole blood cultures reacted strongly with antitubulin antibody but reacted negatively with anti-40 KD garlic protein antibodies and therefore was not related to the 40 KD garlic protein immunocytochemically.

J Antibiot (Tokyo), 1995 Aug, 48(8), 773 - 9
AL072, a novel anti-Legionella antibiotic produced by Streptomyces sp; Yon C et al.; AL072 is a potent anti-Legionella antibiotic produced by Streptomyces strain AL91 . The compound was isolated from the fermentation broth with 1 volume of isopropyl alcohol, followed by an ethyl acetate extraction and subsequent concentration under reduced pressure . Purification was performed on an octadecyl silica gel column followed by preparative HPLC . AL072 purified as mentioned above showed extremely specific activity only towards Legionella pneumophila . No antibacterial activity against any other bacteria tested was demonstrable . Its molecular weight was determined by FAB-MS (m/z 648) and the compound was identified as a novel 1,3-diacyl glycerol with the molecular formula C41H76O5 . One of the two acyl groups is linoleyl and the other is 3,5-dimethyl octadecanoyl.

Drug Saf, 1995 Aug, 13(2), 105 - 22
Macrolide antibacterials . Drug interactions of clinical significance; von Rosensteil NA et al.; Macrolide antibiotics can interact adversely with commonly used drugs, usually by altering metabolism due to complex formation and inhibition of cytochrome P-450 IIIA4 (CYP3A4) in the liver and enterocytes . In addition, pharmacokinetic drug interactions with macrolides can result from their antibiotic effect on microorganisms of the enteric flora, and through enhanced gastric emptying due to a motilin-like effect . Macrolides may be classified into 3 different groups according to their affinity for CYP3A4, and thus their propensity to cause pharmacokinetic drug interactions . Troleandomycin, erythromycin and its prodrugs decrease drug metabolism and may produce drug interactions (group 1) . Others, including clarithromycin, flurithromycin, midecamycin, midecamycin acetate (miocamycin; ponsinomycin), josamycin and roxithromycin (group 2) rarely cause interactions . Azithromycin, dirithromycin, rikamycin and spiramycin (group 3) do not inactivate CYP3A4 and do not engender these adverse effects . Drug interactions with carbamazepine, cyclosporin, terfenadine, astemizole and theophylline represent the most frequently encountered interactions with macrolide antibiotics . If the combination of a macrolide and one of these compounds cannot be avoided, serum concentrations of concurrently administered drugs should be monitored and patients observed for signs of toxicity . Rare interactions and those of dubious clinical importance are those with alfentanil and sufentanil, antacids and cimetidine, oral anticoagulants, bromocriptine, clozapine, oral contraceptive steroids, digoxin, disopyramide, ergot alkaloids, felodipine, glibenclamide (glyburide), levodopa/carbidopa, lovastatin, methylprednisolone, phenazone (antipyrine), phenytoin, rifabutin and rifampicin (rifampin), triazolam and midazolam, valproic acid (sodium valproate) and zidovudine.

Biol Chem Hoppe Seyler, 1995 Aug, 376(8), 507 - 10
Molecular cloning and identification of a novel porcine cathelin-like antibacterial peptide precursor; Strukelj B et al.; A novel clone (C6) encoding the precursor of a 79-residue proline/arginine-rich antibacterial peptide prophenin was isolated from a porcine bone marrow cDNA library . Its deduced N-terminal propart shows 84% identity with cathelin . Additionally, two cathelin isoforms were isolated from peripheral porcine blood and their N-termini sequenced . The sequence of one isoform corresponds to the cathelin sequence, whereas that of the other protein is identical to the propeptide of C6 clone . Western blot analysis of total proteins from porcine and human bone marrow using polyclonal antibodies against cathelin revealed the presence of immunochemically related high molecular mass proteins of about 30 kDa in both samples, whereas low molecular mass proteins of approximately 12 kDa, corresponding to isolated cathelin, were not detected in human bone marrow.

Immun Infekt, 1995 Aug, 23(4), 125 - 9
{Efficacy of acellular pertussis vaccines}; Wirsing von Konig CH et al.; Acellular vaccines against pertussis could be developed because various virulence factors of B . pertussis have been characterized . Acellular pertussis vaccines should retain the efficacy but have lower side effects, as compared to the conventional whole-cell vaccine . Lacking any correlate of antibacterial resistance, the efficacy of the vaccines had to be tested in large field trials . Such trials have been conducted and are being conducted in various European and in one African country . These trials used different designs, and various different vaccines were tested . All available efficacy data show that acellular pertussis vaccine can effectively protect against typical pertussis . It also seems probable that the efficacy of vaccines, which contain more than two pertussis components may be better than a vaccine containing pertussis toxoid or pertussis toxoid with filamentous hemagglutinin . A three-component acellular pertussis vaccine has been licensed for use in primary vaccination in infants in Germany in early 1995.

Nat Struct Biol, 1995 Aug, 2(8), 644 - 53
An enzyme-substrate complex involved in bacterial cell wall biosynthesis; Benson TE et al.; The crystal structure of UDP-N-acetylenolpyruvylglucosamine reductase in the presence of its substrate, enolpyruvyl-UDP-N-acetylglucosamine, has been solved to 2.7 A resolution . This enzyme is responsible for the synthesis of UDP-N-acetylmuramic acid in bacterial cell wall biosynthesis and consequently provides an attractive target for the design of antibacterial agents . The structure reveals a novel flavin binding motif, shows a striking alignment of the flavin with the substrate, and suggests a catalytic mechanism for the reduction of this unusual enol ether.

J Gastroenterol, 1995 Aug, 30(4), 461 - 4
A proton pump inhibitor, E3810, has antibacterial activity through binding to Helicobacter pylori; Hirai M et al.; Helicobacter pylori infection is causally related to atrophic gastritis, and it may also be associated with peptic ulcer and gastric carcinoma . Eradication of H.pylori is recommended in patients with such diseases, especially in those with peptic ulcer . A new potent proton pump inhibitor, E3810, had an antibacterial effect on H . pylori, as has been reported for omeprazole and lansoprazole, two other proton pump inhibitors . The minimum inhibitory concentration of E3810 was 1.57-3.13 micrograms/ml, lower than that of omeprazole or lansoprazole . To clarify the mechanism of the antibacterial effect of E3810, we analyzed the characteristics of E3810 binding to H . pylori . Scatchard plot analysis of this binding showed a curvilinear profile, indicating the presence of several molecules with different affinities to E3810 on H . pylori . The binding capacity of E3810 to H . pylori was calculated to be about 2 x 10(6) sites/cell . These results suggested that E3810 has an antibacterial effect against H . pylori and that the effect may be mediated through direct binding to H . pylori.

Eur J Gastroenterol Hepatol, 1995 Aug, 7(8), 717 - 23
Gastroparesis and dyspepsia in patients with diabetes mellitus; Mearin F et al.; About one-half of patients with insulin- or non-insulin-dependent diabetes have delayed gastric emptying (diabetic gastroparesis) . Some of them complain of epigastric pain, nausea, vomiting or postprandial fullness (diabetic dyspepsia), although only a minority are severely symptomatic . Diabetic gastroparesis is clinically relevant not only by virtue of the symptoms induced but also because it may contribute to inadequate glycaemic control and impaired absorption of orally administered drugs . Recent data suggest that abnormal blood glucose control, not only autonomic neuropathy, contribute to the pathogenesis of disordered gastric motility . In most cases diabetic gastroparesis is diagnosed clinically in the absence of demonstrable lesions of the upper gastrointestinal tract . To evaluate gastric emptying, scintigraphy is the 'gold standard' . Gastrokinetic drugs are of help in the treatment of gastroparesis: erythromycin is the first choice in acute presentations and cisapride for chronic symptoms . New macrolides with prokinetic action and devoid of antibacterial properties are very promising and should add another pharmacologic approach to control dyspepsia and gastroparesis in diabetic patients in the future.

FEBS Lett, 1995 Jul 24, 368(3), 485 - 7
Molecular cloning of cDNA for sapecin B, an antibacterial protein of Sarcophaga, and its detection in larval brain; Lee SR et al.; A cDNA clone for sapecin B, an antibacterial protein of Sarcophaga, was isolated . This cDNA encoded a precursor protein of sapecin B consisting of a signal sequence (24 residues), prosegment (30 residues) and mature sapecin B (34 residues) . Sapecin B was synthesized almost exclusively in the fat body when the larval body wall was injured, but the brain of naive larvae was also demonstrated to contain a significant amount of sapecin B . These findings suggested that sapecin B is a bifunctional protein.

J Med Chem, 1995 Jul 21, 38(15), 2974 - 7
Effect of lipophilicity at N-1 on activity of fluoroquinolones against mycobacteria; Renau TE et al.; The dramatic increase in drug resistant Mycobacterium tuberculosis has caused a resurgence in research targeted toward these organisms . As part of a systematic study to optimize the quinolone antibacterials against mycobacteria, we have prepared a series of N-1-phenyl-substituted derivatives to explore the effect of increasing lipophilicity on potency at this position . The compounds, synthesized by the modification of a literature procedure, were evaluated for activity against Gram-negative and Gram-positive bacteria, Mycobacterium fortuitum and Mycobacterium smegmatis, and the results correlated with log P, pKa, and other attributes . The activity of the compounds against the rapidly growing, less hazardous organism M . fortuitum was used as a measure of M . tuberculosis activity . The results demonstrate that increasing lipophilic character by itself does not correlate with increased potency against mycobacteria . Rather, intrinsic activity against Gram-negative and/or Gram-positive bacteria is the governing factor for corresponding activity against mycobacteria.

Biochem Biophys Res Commun, 1995 Jul 17, 212(2), 589 - 94
Inhibition of diamine oxidase activity by metronidazole; Befani O et al.; Metronidazole was found to be a non-competitive inhibitor of man, rabbit and rat intestinal diamine oxidases with an inhibition constant value of approximately 10(-4) M . The purified bovine serum amine oxidase was not inhibited, whereas the purified swine kidney enzyme gave similar results . These findings suggest that metronidazole and similar compounds, used as antibacterial and antiprotozoal drugs, should be given under careful control, especially when administered for long times, because a decrease of intestinal diamine oxidase activity was proven to be a risk factor for several pathologies of this organ.

Br Dent J, 1995 Jul 8, 179(1), 28 - 34
Non-surgical periodontal therapy: essential and adjunctive methods; Greene PR; The presence of bacterial deposits on teeth has been observed since the birth of microbiology but it has taken over 300 years to understand which elements of the various hard and soft dental deposits must be removed in order to arrest the destructive processes caused by the periodontal diseases . This article reviews the current state of knowledge regarding non-surgical periodontal therapy, including adjuncts such as mouthrinses and antibacterials and considers when other treatment modalities would be beneficial for the patient.

Minerva Ginecol, 1995 Jul-Aug, 47(7-8), 335 - 9
{Piperacillin in prevention and therapy in gynecological surgery}; Giannone R et al.; The authors have studied the use of sodic piperacillin in surgical gynecological prophylaxis . The drug, used in the intravenous tract, has proved efficacious for broad spectrum of antibacterial action versus gram+, gram-, and anaerobic and aerobic . It has shown an excellent tolerability by reducing hospital surgical infections (11% of cases) and sepsis (9.2% of cases) with social, economic and professional advantages.

Indian J Physiol Pharmacol, 1995 Jul, 39(3), 247 - 51
A comparative study of prescribing pattern at different levels of health care delivery system in Bangalore district; Srishyla MV et al.; A study of prescribing pattern in tertiary, primary and urban general practice levels of the Indian health care delivery system was undertaken by analyzing 1810 prescriptions for 3932 drugs . The study evaluated feasibility of data acquisition methods and compared the prescribing frequency of various drug groups and of individual drugs in three commonly used categories . The mean number of drugs per prescription was highest in urban general practice (2.41) . The four most frequently prescribed drug groups were antibacterials, vitamins, nonsteroidal antiinflammatory drugs (NSAIDs) and respiratory drugs . The study delineates the differences in prescribing frequency of drug groups and individual drugs across the three levels of health care and the results suggest intervention strategies to promote rational drug therapy.

J Antimicrob Chemother, 1995 Jul, 36(1), 185 - 200
Equivalent efficacies of meropenem and ceftazidime as empirical monotherapy of febrile neutropenic patients . The Meropenem Study Group of Leuven, London and Nijmegen; Outbreaks of proliferative haemorrhagic enteropathy on two pig farms; Bendigo Agriculture Centre, VictoriaClinical signs of proliferative haemorrhagic enteropathy (PHE) including anaemia, dysentery and sudden death were observed in finisher pigs and young breeding stock on 2 farms . On farm A, PHE occurred 12 months after repopulation of the farm . Other outbreaks of PHE occurred after the withdrawal of therapeutic concentrations of in-feed antibacterial agents (farm A), or after monensin sodium (100 g/t) replaced olaquindox (100 g/t) in feed (farm B) . The outbreaks, the possible sources of contamination and the role of antibacterial feed additives in the treatment and control of PHE are described.

J Antibiot (Tokyo), 1995 Jul, 48(7), 676 - 82
Unusual transformation of the 3-hydroxy-picolinoyl residue of pristinamycin IA; Paris JM et al.; Pristinamycin IA was modified in a two-step procedure to give original derivatives possessing a tricyclic nucleus (8a, 8b, 8c) or a substituted pyrrole ring (10a, 10b) in place of the natural exocyclic 3-hydroxy-picolinoyl residue . This transformation involved firstly preparation of pyridinium betaines 5 from pristinamycin IA and secondly a 1-3 dipolar cycloaddition between 5 and N-substituted maleimides or diethyl acetylenedicarboxylate . The compounds obtained were evaluated as antibacterial agents alone and in association with pristinamycin IIA.

J Antibiot (Tokyo), 1995 Jul, 48(7), 667 - 70
Chemical modification of tylosin; Bobillot S et al.; 20-Homo tylosin, 20-nor tylosin, 20-deoxy-19,20-didehydro tylosin (6-vinyl tylosin) and 2",3"-didehydro-3"-deoxy tylosin were prepared by multi-step procedures . 20-Homo tylosin was about twice less active than tylosin while the other compounds exhibited very weak antibacterial activity.

Clin Pharmacokinet, 1995 Jul, 29(1), 15 - 28
Clinical pharmacokinetics in patients with burns; Jaehde U et al.; Burn injury induces many different pathological changes in the human body, which potentially alter pharmacokinetic parameters such as bioavailability, protein binding, volume of distribution (Vd) and clearance . The extent of these alterations depends on the drug, the type and extent of injury and the time that elapsed between injury and drug administration . Bioavailability of large and hydrophilic molecules may be increased because of enhanced intestinal permeability . The free fraction of a drug in plasma can be increased (when primarily bound to albumin) or decreased (when primarily bound to alpha 1-acid glycoprotein) . Vd may change as a consequence of altered protein binding or an enlarged extracellular fluid volume . Alterations in clearance may be due to changes in glomerular filtration, tubular secretion, hepatic blood flow, drug-metabolising activity, protein binding and to the presence of additional elimination pathways . Elimination half-life changes when Vd and/or clearance is affected following burn injury . The therapeutic consequences of pharmacokinetic alterations are discussed in principle, and for specific treatment with antibacterials, anti-ulcer drugs, analgesics, muscle relaxants, anxiolytics, phenytoin and cyclosporin . If significant changes in pharmacokinetic disposition occur following thermal injury, therapeutic drug monitoring and dosage adjustment may be required to ensure rational and well tolerated drug therapy in patients with burns . Future studies should focus on the impact of specific patient variables (e.g . type of injury and size of burn) on the extent of pharmacokinetic alterations.

Chem Pharm Bull (Tokyo), 1995 Jul, 43(7), 1238 - 40
Studies on pyridonecarboxylic acids . IV . Synthesis and antibacterial activity evaluation of S-(-)- and R-(+)-6-fluoro-1-methyl-4-oxo-7- (1-piperazinyl)-4H-{1,3} thiazeto{3,2-a}quinoline-3-carboxylic acids; Segawa J et al.; Optically active isomers of 6-fluoro-1-methyl-4-oxo-7-(1-piperazinyl)-4H- {1,3} thiazeto {3,2-alpha} quinoline-3- carboxylic acid (NM394, 3) were prepared through optical resolution of their racemic intermediate ( +/- )-1 by high-performance liquid chromatography (HPLC) . The absolute configuration at the C-1 position in the thiazeto-quinolone ring of ( - )-3 was confirmed by X-ray analysis ( - )-4 to be S . The in vitro antibacterial activity of ( - )-3 was 2--8 times that of (+)-3.

Clin Diagn Lab Immunol, 1995 Jul, 2(4), 503 - 5
Immunomodulatory effects of alpha interferon and thymostimulin in patients with neoplasias; Munno I et al.; In this report, we have evaluated the immunological effects following administration of alpha interferon (IFN-alpha) in combination with thymostimulin (TP-1), as well as of IFN-alpha and TP-1 alone in patients with neoplasias who underwent surgery and were subsequently treated with conventional chemotherapy . Data suggest that the combination of IFN-alpha and TP-1 is the most effective in the up-regulation of some immune parameters such as the CD4(+)-CD8+ cell-dependent antibacterial activity . Since this immune function plays an important role in the host protection against different targets such as invading microorganisms and/or neoplastic cells, the administration of TP-1-IFN-alpha is advisable for patients with neoplasias under chemotherapy.

Vnitr Lek, 1995 Jul, 41(7), 498 - 503
{New findings on the classification, diagnosis and therapy of primary gastrointestinal lymphomas}; Krc I et al.; Based on available recent data from the literature the authors review recent findings pertaining to the etiopathogenesis, immunology, clinical manifestations and treatment of primary gastrointestinal lymphomas . From the pathogenetic aspect in particular the close association with infections and immune disorders in various portions of the gastrointestinal tract is important . In their review the authors draw attention to new aspects of the histological and immunological classification of these tumors, in particular as far as definition of lymphomas of the MALT-system is concerned . They evaluate also data from their own group of 83 patients with regard to the incidence and site of the disease . In the conclusion they draw attention to the importance of some new therapeutic approaches, incl . antibacterial treatment.

Thorax, 1995 Jul, 50(7), 739 - 45
Microbial inciters of acute asthma in urban Nigerian children; Gbadero DA et al.; BACKGROUND--In tropical Africa the role of microbial agents of acute respiratory infections in acute exacerbations of bronchial asthma remains largely unexplored . However, empirical antibacterial therapy is frequently initiated in moderate to severe cases of acute asthma with symptoms of acute respiratory infection . A study was set up to determine how often acute respiratory infection is associated with acute asthma, to identify the associated pathogens, and to proffer appropriate therapeutic suggestions . METHODS--Over a 16 month period, 86 episodes of acute asthma were studied for clinical and laboratory features of acute respiratory infection at the University College Hospital (UCH), Ibadan . Virological diagnosis was based on immunofluorescence studies of nasopharyngeal aspirates and/or serological tests using the microtitre complement fixation technique . Throat swabs and blood were cultured for bacterial agents . RESULTS--Of the 64 cases who presented with rhinorrhoea, 51 (79.7%) were pyrexial (T > or = 37.6 degrees C) . Inflammatory changes (frequently interstitial streakiness) were identified in 10 (19.6%) of the 51 chest radiographs; only two of these had lobar shadowing . Significant bacterial isolates were made in only three (3.5%) of the throat swabs and two (2.4%) of the blood cultures from the 86 cases; none had clinical septicaemia . On the other hand, 55 viral agents were identified from 39 (53%) of the 74 subjects studied; 16 (41.0%) had dual viral identifications . Respiratory syncytial virus (RSV) accounted for 20 (36.4%) identifications, parainfluenza virus (PIV) type 3 for 15 (27.3%), and influenza type A (Flu A) for 12 (21.8%) . Viral identifications were significantly higher in infants and preschool subjects (< 5 years) and in those presenting with either rhinorrhoea or pyrexia . CONCLUSIONS--The results of this study underscore the importance of viral upper respiratory infections in asthma exacerbations in a tropical setting . The paucity of clinical and investigative features of bacterial acute respiratory infection suggests that there is little rationale for routine antibiotic cover in children with acute exacerbations of asthma in the tropics.

J Nat Prod, 1995 Jul, 58(7), 1131 - 5
Sesquiterpene/quinol from a New Zealand liverwort, Riccardia crassa; Perry NB et al.; A new sesquiterpene/quinol, with mild cytotoxic and antibacterial activity, has been isolated from a New Zealand collection of the liverwort Riccardia crassa . The structure of this compound, riccardiphenol C {3}, was established by nmr spectroscopy . Closely related compounds previously isolated from a Japanese collection of R . crassa were not detected in this collection.

J Clin Pharmacol, 1995 Jul, 35(7), 647 - 54
Helicobacter pylori and gastrointestinal disease; Gibaldi M; New paradigms are few and far between . The discovery that peptic ulcer disease is the result of an infection by a previously unrecognized microorganism rather than the consequence of excess secretion of gastric acid aptly qualifies as a paradigm shift . Eradication of Helicobacter pylori from the stomach by antibacterial agents heals ulcers at least as effectively as H2-blockers . Further, eradication of the organism results in long-term cures of peptic ulcers . In contrast, the relapse rate in patients successfully treated with H2-blockers exceeds 50% in the first year after healing . Also of interest is the role of H . pylori in gastric cancer.

J Clin Periodontol, 1995 Jul, 22(7), 533 - 9
Plaque formation and gingivitis after mouthrinsing with 0.2% delmopinol hydrochloride, 0.2% chlorhexidine digluconate and placebo for 4 weeks, following an initial professional tooth cleaning; Hase JC et al.; A double-blind, randomised, 4-week clinical trial with parallel group design in 57 patients with gingivitis was conducted for studying the antibacterial efficacy and safety of a delmopinol HCl aqueous solution 2 mg/ml (0.2% w/v), which was used for unsupervised mouth-rinsing and compared with placebo and chlorhexidine digluconate 2 mg/ml (0.2% w/v, Hibitane Dental, ICI Pharmaceuticals, UK).The plaque index and plaque wet weight were used to measure plaque formation, and gingival fluid flow and bleeding on probing to measure gingivitis . According to the reduction from baseline, chlorhexidine showed a significantly better effect on plaque formation than the placebo after 4 weeks treatment for both plaque measurements . Delmopinol exhibited significantly lower plaque index scores than placebo . The difference between chlorhexidine and delmopinol was not statistically significant for any of the plaque measurements . For gingivitis, no statistically significant differences were obtained between the effects of delmopinol, chlorhexidine and placebo . A transient anaesthetic sensation in the oral mucosa was experienced more clearly by the patients in the delmopinol group than by those using chlorhexidine or placebo rinses . Rinsing with chlorhexidine resulted in more staining of the teeth and tongue than did delmopinol and placebo . The placebo solution tasted better than the 2 active solutions . The results showed that rinsing with either delmopinol HCl aqueous solution 2 mg/ml or chlorhexidine digluconate 2 mg/ml 2x daily for 60 as a supplement to normal oral hygiene, following an initial professional tooth cleaning, leads to a lower plaque formation than rinsing with placebo.(ABSTRACT TRUNCATED AT 250 WORDS)

Chemotherapy, 1995 Jul-Aug, 41(4), 253 - 6
Antibacterial activity of azithromycin against Brucella melitensis; Qadri SM et al.; In vitro antibacterial activity of the new macrolide azithromycin was tested against 116 strains of Brucella melitensis, isolated from 115 patients in a major tertiary care referral center . Eighty-seven percent of the strains were inhibited by 1.0 mg/l and all the 116 strains by 2.0 mg/l of azithromycin . Comparison was made with tetracycline, gentamicin, trimethoprim-sulfamethoxazole, rifampicin and ciprofloxacin . All the isolates were susceptible to gentamicin, tetracycline, trimethoprim-sulfamethoxazole, rifampicin . One hundred and fifteen of the 115 strains were also susceptible to ciprofloxacin.

Chemotherapy, 1995 Jul-Aug, 41(4), 239 - 46
Bactericidal kinetics of an in vitro infection model of once-daily ceftriaxone plus amikacin against gram-positive and gram-negative bacteria; Scaglione F et al.; The in vitro efficacy of ceftriaxone plus amikacin combination against gram-positive and gram-negative bacteria, clinically isolated from patients affected by pneumonia in intensive care units, was compared to that of the 2 drugs used alone . The study was performed using a dynamic model in which the human kinetics of the drugs after intramuscular administration was simulated . The antibacterial activity was tested by determining the bacterial cell count (CFU/ml) . Killing curves came out from plotting the log CFU/ml versus time . In the same way, ceftriaxone and amikacin concentrations were assayed by HPLC and fluorescence polarization immunoassay, respectively . The results show that ceftriaxone plus amikacin combination exert a high killing activity against all tested strains . The two antibiotics alone initially have a good killing activity but this is followed by bacterial regrowth for all tested isolates . This data supports the results of several clinical studies which have shown a good therapeutic efficacy of ceftriaxone plus amikacin combination in the treatment of severe infections caused by organisms intermediately sensitive to these drugs.

Biochem Pharmacol, 1995 Jun 29, 50(1), 111 - 22
Mechanism of action and antitumor activity of (S)-10-(2,6-dimethyl-4-pyridinyl)-9-fluoro-3-methyl-7-oxo-2,3-dihydro-7 H- pyridol{1,2,3-de}-{1,4}benzothiazine-6-carboxylic acid (WIN 58161); Coughlin SA et al.; (S)-10-(2,6-Dimethyl-4-pyridinyl)-9-fluoro-3-methyl-7-oxo-2,3-dihydro-7H - pyrido{1,2,3-de}{1,4}benzothiazine-6-carboxylic acid (WIN 58161) is an enantiomerically pure quinolone with outstanding bacterial topoisomerase II (DNA gyrase, EC 5.99.1.3) inhibitory and antibacterial activity . Unlike most quinolones, WIN 58161 also exhibits significant inhibitory activity against mammalian topoisomerase II (EC 5.99.1.3) . DNA gyrase and topoisomerase II inhibitory activities are enantioselective . Consequently, WIN 58161 and its enantiomer (WIN 58161-2) provide useful tools to probe the contribution of topoisomerase II inhibition to the mechanism of cytotoxicity of quinolones and the potential utility of quinolone-topoisomerase II inhibitors as antitumor agents . WIN 58161 inhibited both highly purified Escherichia coli DNA gyrase and HeLa cell topoisomerase II by the promotion of enzyme-DNA covalent complexes . WIN 58161 did not bind stably to DNA via intercalation and did not enhance the formation of topoisomerase I (EC 5.99.1.2)-DNA covalent complexes . At drug concentrations that are cytotoxic to P388 murine leukemia cells, WIN 58161 promoted intracellular DNA single-strand breaks (SSBs) that exhibited the hallmarks of being mediated by topoisomerase . DNA fragments were complexed with protein, and SSBs were readily resealed at 37 degrees following drug removal . WIN 58161-2 was neither cytotoxic nor did it promote intracellular SSBs in P388 . These observations suggest that the mechanism of cytotoxicity of WIN 58161 is predominantly, if not exclusively, a result of topoisomerase II inhibition . When studied in tumor-bearing mice, WIN 58161 exhibited a significant antitumor effect against each of five tumors tested, whereas neither toxicity nor antitumor activity was observed with WIN 58161-2 . We conclude from these studies that WIN 58161 represents the prototype of a novel chemical class of topoisomerase II inhibitor with potential clinical utility in treating cancer.

J Biol Chem, 1995 Jun 16, 270(24), 14493 - 9
A novel type of limulus lectin-L6 . Purification, primary structure, and antibacterial activity; Saito T et al.; Lipopolysaccharide (LPS)-binding protein(s) was first screened in the detergent extract of horseshoe crab (limulus) hemocytes using LPS-immobilized agarose . A protein, designated L6 (M(r) = 27,000), was found to bind to LPS-agarose and was eluted with EDTA or o-phenanthroline . The L6 protein, however, did not inhibit the LPS-mediated activation of a limulus serine protease zymogen factor C . L6 had an affinity to the matrix of Sepharose CL-6B itself, and it could be eluted with high concentrations of monosaccharides (0.5-1.0 M), such as glucose, mannose, and galactose, suggesting a lectin-like nature . The entire amino acid sequence of L6 was determined by sequencing peptides derived from CNBr and enzymatic cleavages . L6 contained 7 half-cystines, and 1 cysteine residue at position 201 had a free SH-group . In addition, positions of the remaining three intrachain disulfide bonds were assigned by amino acid and sequence analyses of three cystinyl peptides produced by lysyl endopeptidase digestion . These results indicated that the entire sequence of L6 consisted of 221 residues with no N-linked sugar and was composed of six tandem repeats, each consisting of 33-38 amino acid residues . Inductively coupled plasma spectrometry of L6 indicated the presence of 0.75 mol zinc/mol of protein . No significant sequence homology was observed between L6 and other proteins, including various animal lectins and LPS-binding proteins . However, L6 showed agglutinating activity on LPS-coated sheep erythrocytes and Gram-negative and Gram-positive bacteria, it inhibited the growth of Gram-negative bacteria, and thus it presumably recognizes carbohydrate components in the cell wall of bacteria.

Biochemistry, 1995 Jun 6, 34(22), 7394 - 400
Insect immunity . The inducible antibacterial peptide diptericin carries two O-glycans necessary for biological activity; Bulet P et al.; A bacterial challenge of larvae of the dipteran insect Phormia terranovae induces the rapid synthesis of diptericin, an antibacterial polypeptide, previously characterized at the amino acid level and indirectly by cDNA cloning studies . This 82-residue polypeptide consists of an N-terminal proline-rich domain and a central and C-terminal glycine-rich domain . Using liquid chromatography coupled to electrospray ionization-mass spectrometry, we demonstrate here that this molecule is more complex than anticipated and carries two O-substitutions on threonine residues, one in the proline-rich domain (residue 10) and one in the glycine-rich domain (residue 54) . These substitutions consist of identical trisaccharides: glucose-->galactose-->N-acetylgalactosamine-->(threonine) . Treatment of diptericin with O-glycosidase, which selectively removes the substitutions without altering the polypeptide proper, abolishes the antibacterial activity, indicating that this posttranslational modification is essential for biological activity of the polypeptide . We also show that diptericin is posttranslationally modified by a C-terminal amidation.

Lijec Vjesn, 1995 Jun, 117 Suppl 2, 16 - 21
{Treatment of septic shock in pediatrics}; Novak M; A significant improvement has been noticed over the last 20 years in children in whom shock syndrome has developed . This has been attained through the application of technological advances in respiratory, cardiovascular, renal, nutritional support and improved antibacterial and antifungal therapy, but mostly through a better understanding of the physiology of shock . Newer concepts of the pathophysiology of sepsis and septic shock are presented, with clinical definitions referring to the pediatric patient . Innovative therapeutic modalities designed to modulate the systemic inflammatory response triggered by bacterial infection are discussed.

Antibiot Khimioter, 1995 Jun, 40(6), 31 - 6
{Methods for rapid evaluation of the effectiveness of drugs showing promise for urgent prevention and treatment of plague}; Romanov VE et al.; The choice of efficient antibacterial drugs useful in special prophylaxis and treatment of plague includes the stage of the in vivo screening whose main disadvantages are long-term and hazardous tests . The paper presents the data showing that a useful chemotherapeutic for the treatment of plague could be safely screened within 48-72 hours . The methods are based on two-fold retrobulbar or intraperitoneal administration of a drug within 24 hours to albino mice infected with highly virulent strains of Y . pestis . The dose should not exceed 1.10(7) live microbes . It was shown that the administration of the plague microbes to albino mice simultaneously with ferrous sulfate lowered the time of the animal death and accelerated the efficacy estimation of the drug.

Antibiot Khimioter, 1995 Jun, 40(6), 23 - 30
{Standardization of conditions for the evaluation of effectiveness of antibacterial drugs in pneumonic plague in sacred baboons}; Romanov VE et al.; The signs of pneumonic plague in sacred baboons infected by aerosol are: fever, hurried breathing, depression and constantly increasing bacteremia . Some infected animals isolate the plague microbes while coughing and thus could be a source of the infection . By the clinical and pathomorphological signs, pneumonic plague in sacred baboons is similar to that in humans which makes it possible to use the animals in the development of schemes for special prophylaxis and treatment of the disease . In efficacy estimation of antibacterial drugs sacred baboons should be infected by aerosol by highly virulent strains of Y . pestis in doses of 1.10(4)-1.10(5) live microbes . The treatment of the animals should be started from the moment of the rectal temperature increase to 39.5 degrees C or higher after collecting the blood specimens for the bacteriological tests . It was shown that a two-day course of the treatment with antibacterial drugs was not efficient in the animals with pneumonic plague . The use of streptomycin, gentamicin, netilmicin or ciprofloxacin for 7 days cured all the infected animals . The use of streptomycin in the therapeutic doses was not efficient in the animals whose blood specimens of 1 cm3 contained 4.10(4) or more plague microbes by the moment when the treatment was started.

Chest, 1995 Jun, 107(6), 1681 - 5
Transferrin concentrations in serum and lower respiratory tract fluid of mechanically ventilated patients with COPD or ARDS; Stites SW et al.; Transferrin serves as the primary iron transport protein in serum, but it also is present in the lower respiratory tract where it has antioxidant and antibacterial properties . Prior studies indicate that patients with respiratory failure (RF) due to ARDS have increased concentrations of transferrin in the lower respiratory tract, which is attributed to increased lung vascular permeability . It is unclear whether mechanical ventilation contributes to increased lung transferrin content in patients with ARDS, although mechanical ventilation may increase lung microvascular permeability . To assess whether mechanical ventilation in patients with RF due to causes other than ARDS is also associated with increased respiratory tract concentrations of transferrin, we compared transferrin concentrations in serum and lung lavage fluid obtained from 12 mechanically ventilated patients with RF attributable to COPD, 6 patients with ARDS, and 15 healthy volunteers . Serum transferrin concentrations in patients with RF due to COPD were variable, but mean concentrations were similar to those in control subjects (336 +/- 58 vs 307 +/- 9 {SE} mg/dL), whereas serum transferrin concentrations were decreased in patients with ARDS (182 +/- 68 mg/dL; p < 0.05) . Compared with control subjects, lavage fluid recovered from patients with RF due to COPD contained significantly decreased concentrations of transferrin (1.56 +/- 0.24 vs 4.27 +/- 0.44 micrograms/mL; p < 0.001), whereas transferrin concentrations in lavage fluid recovered from patients with ARDS were increased (15.72 +/- 2.01 micrograms/mL; p < 0.001) . Transferrin concentrations of lavage fluid also were decreased in COPD patients when normalized for lavage fluid protein content (4.35 +/- 0.72 vs 19.96 +/- 3.13 micrograms/mg in control subjects, p < 0.001) . These data indicate that mechanical ventilation of patients with COPD is associated with decreased lung transferrin concentrations, in contrast to an increased transferrin concentration found in patients with ARDS . Decreased transferrin concentrations in the lower respiratory tract may decrease defenses against oxidant injury and bacterial infection in patients with RF due to COPD.

Arch Pharm (Weinheim), 1995 Jun, 328(6), 551 - 5
Synthesis and antibacterial activity of 7 beta-{3-(un)substituted-2-aminopropionamido}-3-vinylcephalosporin s and related compounds; Nestorova B et al.; A series of new 7 beta-{3-(un)substituted-alanyl}-3-vinylcephalosporins and some related compounds, 4a-l is described . They incorporate residues of proteinogenic L-alpha-aminocarboxylic acids, their antimetabolites and enantiomers as well as a dipeptide in the 7 beta-acylamido side chain . The acylation of diphenyl-methyl 7-amino-3-vinyl-3-cephem-4-carboxylate (2: R2 = DPM) with various protected alpha-aminocarboxylic acids 1a-k and the dipeptide 1l is carried out using TBTU as coupling reagent . The compounds, except 4f, are active in vitro against S . aureus and S . lutea, but only 4a, 4k, and 4l inhibit some of the Gram-negative strains.

Nihon Kyobu Shikkan Gakkai Zasshi, 1995 Jun, 33(6), 605 - 11
{Augmentation of immune defense mechanisms of the lung by romurtide}; Hasegawa J et al.; Muramyl dipeptide (MDP), derived from the major constituent of bacterial cell walls, can augment host defense mechanisms, and romurtide {MDP-Lys (L18)}, a synthetic MDP derivative, is thought to be more potent than other MDP derivatives . Therefore, we evaluated whether romurtide can bolster the immune defense mechanisms of the lung . We compared the functions of peripheral blood leukocytes with those of broncho alveolar lavage fluid cells (BALF cell) in DA rats and in patients with lung cancer who were treated with radiation . The results indicate that romurtide can increase the antibacterial activity of BALF cells preferentially and that this adjuvant therapy can help to prevent respiratory infections.

Gesundheitswesen, 1995 Jun, 57(6), 351 - 4
{Transmission of poliomyelitis by drinking water and the problem of prevention}; Knolle H; The role of drinking water as a source of infection with wild poliovirus in modern cities was denied nearly 50 years ago on the basis of arguments taken from bacteriology . Recent findings concerning the persistence of viruses in water and their resistance to antibacterial agents applied to fresh water and waste water require a revision of those older concepts . There is now convincing evidence that in New York City, where poliomyelitis struck with extreme severity, drinking water was a main source of infection . The phenomenon of water-borne poliomyelitis may become important in the near future as well . Since population growth and scarcity of water in many parts of the world makes recycling of waste water necessary, the eradication campaign of the WHO must consider the possibility that strains of vaccine virus excreted by vaccinees will be reproduced forever.

Pediatr Dermatol, 1995 Jun, 12(2), 178 - 83
Clinical pattern of cutaneous drug eruption among children and adolescents in north India; Sharma VK et al.; Various types of cutaneous drug eruptions and the incriminating drugs were analyzed in 50 children and adolescents up to 18 years of age (34 or 65% boys, 16 or 32% girls) . Thirteen (26%) patients had a maculopapular rash, 11 (22%) a fixed drug eruption (FDE), 10 erythema multiforme (EM), 6 (12%) toxic epidermal necrolysis (TEN), 5 (10%) Stevens-Johnson syndrome (SJS), 3 (6%) urticaria, and 2 (4%) erythroderma . The incubation period for maculopapular rashes, SJS and TEN due to commonly used antibiotics and sulfonamides was short, a few hours to two to three days, reflecting reexposure, and for drugs used sparingly such as antiepileptics and antituberculosis agents, was approximately one week or more, suggesting a first exposure . Antibiotics were responsible for cutaneous eruptions in 27 patients, followed by antiepileptics in 17, analgin in 4, and metronidazole and albendazole in 1 each . Cotrimoxazole, a combination of sulfamethoxazole and trimethoprim, was the most common antibacterial responsible for eruptions (11 patients), followed by penicillin and its semisynthetic derivatives (8 patients), sulfonamide alone (3 patients), and other antibiotics (4 patients) . Antiepileptics were the most frequently incriminated drugs in EM, TEN, and SJS . The role of systemic corticosteroids in the management of SJS and TEN is controversial . We administered prednisolone or an equivalent corticosteroid 2 mg/kg/day for 7 to 14 days.(ABSTRACT TRUNCATED AT 250 WORDS)

Chem Pharm Bull (Tokyo), 1995 Jun, 43(6), 955 - 9
Synthesis, antiviral, antibacterial and antitumor cell activities of 2'-deoxy-2'-fluoropuromycin; Maruyama T et al.; A procedure for the synthesis of 2'-deoxy-2'-fluoropuromycin (1b) was developed . Ring opening of the lyxo-epoxide (4) or nucleophilic displacement of the 3'-O-mesylate (5) by an azide ion afforded two azido nucleosides, 6a and 7a . The major product (7a) was reacted with diethylaminosulfur trifluoride (DAST) to give the 2'-fluoronucleoside (8), which was converted to the 3'-aminonucleoside (9) by hydrogenation . Compound 9 was condensed with an amino acid by the conventional method and subsequently deprotected by acid to give 1b . Compounds 1b, 6b and 7b exhibited no selective antiviral activity against several DNA and RNA viruses . Compound 1b had weak antibacterial activity (minimum inhibitory concentration approximately 25-50 micrograms/ml) and was cytotoxic to several tumor cell lines (L1210, Molt 4, CEM) at a concentration of about 5 microM . This antitumor cell activity may be attributed to inhibition of protein biosynthesis.

Chem Pharm Bull (Tokyo), 1995 Jun, 43(6), 1052 - 4
Degradation kinetics of the new antibacterial fluoroquinolone derivative, orbifloxacin, in aqueous solution; Morimura T et al.; The degradation kinetics of orbifloxacin {1-cyclopropyl-5,6,8-trifluoro-1,4-dihydro-7-(cis-3,5-dimethyl-1-pipe raz inyl)-4-oxoquinoline-3-carboxylic acid} was investigated as a function of pH (1.5-10.5), temperature (100-120 degrees C) and buffer concentration (0.05-0.2 M) by means of high-performance liquid chromatography . The degradation of orbifloxacin in aqueous solution followed apparent first-order kinetics under all experimental conditions . No appreciable effect of buffer on the degradation of orbifloxacin was observed for any of the buffer species used in this study . The log k-pH profiles indicated specific-acid and specific-base catalyses and there were inflection points near pH 6 and 9 corresponding to the pKa1 and pKa2 values . From the Arrhenius plots, the activation energies for k'H, k'H2O, kH2O, k"H2O and k"OH were found to be 31.9, 36.9, 23.5, 26.5 and 19.0 kcal/mol, respectively . Arrhenius data obtained from this study showed that the degradation of orbifloxacin at room temperature was negligible at all pH values studied conditions (pH 1.5-10.5).

Chem Pharm Bull (Tokyo), 1995 Jun, 43(6), 1000 - 4
Photodegradation kinetics of the new antibacterial fluoroquinolone derivative, orbifloxacin, in aqueous solution; Morimura T et al.; The photodegradation kinetics of orbifloxacin (1-cyclopropyl-5,6,8-trifluoro-1,4-dihydro-7-(cis-3,5-dimethyl-1-pipe raz inyl)-4-oxoquinoline-3-carboxylic acid) was investigated in aqueous solution at various pH values (1.2-12.5) and at an ionic strength of 0.5 . The photodegradation experiments were performed using a fluorescent or a chemical lamp as a light source and the cumulative number of photons during exposure was determined by a ferrioxalate actinometer . It was found that the photodegradation of orbifloxacin followed apparent first-order kinetics under both types of artificial light . The photodegradation rates of orbifloxacin in a neutral medium were higher than those in acidic and alkaline media . Orbifloxacin was most unstable in solution at pH 7.4, and its degradation half-life was 0.9 h . Also, the log k-pH profile indicated that the photodegradation rate of orbifloxacin was related to the dissociation of the carboxylic and dimethylpiperazinyl groups and the main photo-labile species was the zwitterionic form . In addition, the photodegradation kinetics of the decarboxylated derivative of orbifloxacin in aqueous solution was investigated to determine the effect of the functional groups on the photodegradation of orbifloxacin.

Infusionsther Transfusionsmed, 1995 Jun, 22(3), 159 - 63
The impact of polymorphonuclear neutrophils on the quality of stored cellular blood products; Kruger J; BACKGROUND: Storage of blood affects all blood components . Polymorphonuclear neutrophils (PMNs) are considered the main culprits of the storage lesion . Their prestorage removal improves the quality of blood components . Therefore, they are considered of no use in blood transfusion . However, their reduction may remove important antibacterial defense mechanisms . METHODS: The phagocytic activity of PMNs in whole blood was therefore determined together with additional, sequential changes of granula-specific and cytosolic constituents which they release . Blood from 12 volunteer donors was analyzed for plasma Na+ and K+, pH, LDH, lysozyme, PMN elastase, leukocytes, neutrophils, and neutrophil phagocytosis with Phagotest . RESULTS: Leukocytes decreased from (5.0 +/- 1.4) x 10(3) to (3.3 +/- 1.3) x 10(3) cells/microliter (mean +/- SD), most of them being PMNs . Their phagocytic capacity when rewarmed did not change significantly during the first 24 h of storage, after 3 days it came to a halt . At the same time an increasing fall in plasma sodium and pH became apparent, while plasma potassium, LDH, lysozyme, and elastase all rose by 427%, 235%, 87% respectively 1,479% at day 11 . Together with these marker enzymes an armamentarium of antibiotic proteins, other proteolytic enzymes, and immunoregulatory molecules is released . CONCLUSION: At present, it seems that the bactericidal activity in blood, due to the removal of phagocytic PMNs, does not outweight the clinical benefits of an improved component preparation where storage lesions are minimized and a number of transfusion-associated adverse reactions are avoided.

Eur J Oral Sci, 1995 Jun, 103(3), 179 - 81
Experiments with two-phase plaque-inhibiting mouthrinses; Kjaerheim V et al.; Reports indicate that oil/water mouthrinses with an aqueous phase containing an antibacterial agent, reduce the amount of volatile bacterial products in expiration air compared with aqueous mouthrinses . These systems have not, however, been tested concerning antiplaque activity . The aim of the present study was to examine the plaque-inhibiting effect of a mouthrinse with an aqueous phase containing 0.2% chlorhexidine (CHX) and an oily phase (soya oil) containing 0.3% triclosan . A test panel rinsed with the mouthrinses twice daily for 4 d . The mouthrinse containing CHX and triclosan in two phases was significantly better than the negative control (water) . However, it was not as effective as the rinse consisting of an aqueous phase with chlorhexidine combined with an oily phase without triclosan . A two-phase mouthrinse with soya oil containing 0.3% triclosan was not superior to soya oil alone, and the combination of CHX and triclosan in a two-phase rinse was not as effective as 0.1% CHX alone in water . No beneficial effect on plaque inhibition could thus be found by using a two-phase system with two different antibacterial agents (one water soluble and one lipid soluble) . Soya oil without triclosan rendered higher plaque inhibition than the control, presumably due to formation of a hydrophobic layer on the tooth surfaces.

Planta Med, 1995 Jun, 61(3), 227 - 32
Biological and pharmacological activities and further constituents of Hyptis verticillata; Kuhnt M et al.; Several extracts of Hyptis verticillata and isolated compounds were evaluated for their anti-inflammatory, antibacterial, antisecretory, and cytotoxic properties . The aerial parts yielded (R)-5-hydroxypyrrolidin-2-one and essential oil with the main components alpha-pinene, beta-pinene, and thymol . Spectroscopic methods (UV, IR, 1H-NMR, 13C-NMR, mass, CD) fully characterized (R)-5-hydroxypyrrolidin-2-one, as it was isolated by a bioassay guided fractionation . The essential oil, (R)-5-hydroxypyrrolidin-2-one, as well as the previously isolated rosmarinic acid and dehydropodophyllotoxine contributed to the antibacterial effects of H . verticillata . Furthermore, rosmarinic acid showed significant capillary stabilizing effects . Sideritoflavone inhibited prostaglandin synthase to a significant extent and had antisecretory effects comparable to those of NPPB . The cytotoxicity of the aqueous extract, as demonstrated using KB and HT 29 cell lines, may be of toxicological relevance in cases of internal application.

Eur J Clin Microbiol Infect Dis, 1995 Jun, 14(6), 536 - 9
Combined effect of human neutrophils, ceftazidime and granulocyte colony-stimulating factor on killing of Escherichia coli; Daschner FD et al.; The combination effect of subinhibitory and inhibitory concentrations of ceftazidime, granulocyte colony-stimulating factor (G-CSF) and polymorphonuclear leukocytes (PMNL) against Escherichia coli was investigated . PMNL obtained from healthy volunteers were incubated with different concentrations of G-CSF and ceftazidime for 180 min . The addition of 0.25 x MIC of ceftazidime or 1 x MIC significantly enhanced the bactericidal activity of PMNL . G-CSF at a concentration of 6,000 units/ml led to only a slight improvement in the bactericidal activity of PMNL . The combination of 6,000 units/ml G-CSF and ceftazidime in inhibitory as well as subinhibitory concentrations, however, showed a significant synergistic effect (p < 0.01) on the antibacterial activity of PMNL during the entire incubation period . Combinations of G-CSF and antibiotics could therefore be beneficial for infected patients, especially those with impaired cellular host defence.

J Pharm Sci, 1995 Jun, 84(6), 777 - 82
Biophysical models as an approach to study passive absorption in drug development: 6-fluoroquinolones; Merino V et al.; A preliminary study attempting to assess and explain the intestinal absorption of a series of antibacterial 7-piperazinyl-6-fluoroquinolones is presented . The synthesis, n-octanol partition coefficients, intrinsic rat gut in situ absorption rate constants, and in vitro antibacterial activity data found for these homologous compounds are described . A fluorimetric, reverse-phase HPLC method was performed for the quantification of the quinolones in absorption and partition samples . Equations based on two classic biophysical absorption models are given for predicting the intrinsic absorption features of the series according to the partition data or merely single structural parameters . In situ absorption rate constants were found to increase by a factor of 9.7-13.5 for moderately lipophilic derivatives relative to the simplest compound, while antibacterial activity decreased only by a factor of 4 . In vivo absorption tests with two representative members of the series were carried out and the results showed a good accordance with those found in situ . This makes these compounds or related ones with similar partition features excellent candidates for further pharmacokinetic and pharmacological testing . The study can serve as an example of how to prevent potential absorption problems associated with the development of new drugs.

APMIS, 1995 Jun, 103(6), 401 - 15
Some new aspects of molecular mechanisms of cyclosporin A effect on immune response; Zav'yalov VP et al.; A few protein targets were found to display a specific high-affinity interaction with the immunosuppressant cyclosporin A (CsA): cytosolic cyclophilins (CyP)A, B, C, D, E containing from 122 to 174 amino acid residues in a polypeptide chain, and secreted forms of CyP; CyP-40, 40-kDa CsA-binding polypeptide complexed with steroid receptor (SR); CyP-related 150-kDa receptor of natural killer (NK) cells; interleukin 8 (IL-8); actin; a family of molecular chaperones hsp70 and P-glycoprotein (P-GP) . All CyPs possess peptidyl-prolyl cis-trans isomerase activity (PPIase) and may serve as ATP-independent molecular chaperone proteins . The CsA-CyP complexes are specific inhibitors of Ca(2+)-and calmodulin-dependent protein phosphatase calcineurin (CaN) . The inhibition of CaN blocks the activation of genes of IL-2, IL-2R, IL-4, etc . in T cells . In addition, immunosuppressive and/or antiinflammatory activity of CsA can be executed via CyP-40 and hsp 70 complexed with SR, and following the interaction with CyP-related receptor of NK and with IL-8 . CsA binding to CyPC, P-GP and actin may throw light on the biochemical events leading to nephrotoxicity and graft vessel disease, two major side effects produced by CsA . The discovery of the interaction of human immunodeficiency virus type 1 (HIV-1) Gag protein with CyP and effective disruption of this interaction by CsA may be important for our understanding of the pathology caused by this immunosuppressive virus and will inspire therapeutic strategies to nip HIV in the bud . Bacterial immunophilins (ImPs) contribute to the virulence of pathogenic microorganisms . Elucidation of molecular mechanisms of microbial ImPs' action in the pathogenesis of bacterial infections may lead to new strategies for designing antibacterial drugs.

Infect Immun, 1995 Jun, 63(6), 2344 - 6
Involvement of cysteine residues in the biological activity of the active fragments of guinea pig neutrophil cationic peptides; Yomogida S et al.; Guinea pig neutrophil cationic peptides (GNCPs) are single-chain polypeptides with 31 amino acid residues containing six cysteine residues, which exhibit both antibacterial and histamine-releasing activities in vitro . In this study, the role of the sulfhydryl groups in defining the antibacterial and histamine-releasing activities of the active fragments of GNCP-1 (Arg-1 to Tyr-14 {Arg-1-Tyr-14} and Arg-15-Tyr-27 peptides) was examined by using peptides containing alkylated or nonalkylated sulfhydryl groups . Alkylation slightly increased the histamine-releasing activity of the Arg-15-Tyr-27 (RRLGTCIFQNRVY) peptide but abrogated the antibacterial activity . Alkylation of the Arg-1-Tyr-14 (RRCICTTRTCRFPY) peptide similarly reduced the antibacterial activity of this fragment but had minimal effect on the histamine-releasing activity . These findings suggest that cysteine residues with free sulfhydryl groups play an important role in the expression of the antibacterial activity of the active fragments of GNCP-1.

J Biochem (Tokyo), 1995 Jun, 117(6), 1312 - 6
Mode of action of an antibacterial peptide, KLKLLLLLKLK-NH2; Alvarez-Bravo J et al.; Previously, we reported that a synthetic undecapeptide, KLKLLLLLKLK-NH2, and its D-enantiomer have potent bactericidal activities against both Gram-positive and Gram-negative bacteria . Here we examined the mode of action of KLKLLLLLKLK-NH2 with special reference to its effect on bacterial membranes . We found that both the outer and inner membrane of Escherichia coli become permeable to low molecular mass substances when treated with this peptide . Under these conditions, the bacteria lost the ability to synthesize ATP and to transport proline, suggesting that their electrochemical membrane potential was disrupted . This peptide appears to form numerous channels in bacterial membranes that interfere with membrane functions, resulting in cell death.

Tidsskr Nor Laegeforen, 1995 May 20, 115(13), 1610 - 5
{The value of C-reactive protein testing in suspected lower respiratory tract infections . A study from general practice on the effect of a rapid test on antibiotic research and course of the disease in adults}; Melbye H et al.; We wanted to assess whether routine use of a rapid test for C-reactive protein (CRP) could reduce prescription of antibiotics for adults with possible lower respiratory tract infection . 239 patients were randomized into a CRP group, tested with the rapid test (n = 108) and a control group (n = 121) . Before knowing to which group the patient belonged the doctors made a preliminary decision about antibacterial treatment . The C-reactive protein value was then released if the patient belonged to the CRP group, and the therapy could be adjusted in light of the result . Antibacterial courses prescribed during the consultations and in the following three weeks were registered . The clinical course was evaluated by interview after one week and again after three weeks . Antibiotics were prescribed for altogether 56% of the patients in the CRP group and 60% in the control group . The difference was not statistically significant . Prescription of antibiotics was strongly associated with the finding of crackles and wheezes, but not with cough, dyspnoea or chest pain . Slow recovery was associated with high age, absence of fever and a normal value of C-reactive protein . No significant benefit of the CRP test was demonstrated . We discuss whether the doctors made full practical use of the information provided by the test . Bronchial obstruction should probably be considered to be the problem more often in coughing patients with a normal CRP value.

J Immunol, 1995 May 15, 154(10), 5403 - 10
Antibacterial proteins of granulocytes differ in interaction with endotoxin . Comparison of bactericidal/permeability-increasing protein, p15s, and defensins; Levy O et al.; Bactericidal/permeability-increasing protein (BPI), antibacterial 15-kDa protein isoforms (p15s), and defensins (neutrophil peptides or NPs) are granule-associated antibacterial proteins of polymorphonuclear leukocytes (PMN) that have both direct and synergistic growth inhibitory activity against Gram-negative bacteria . In this study, we have compared in vitro the abilities of these antibacterial proteins, alone and in combination, to inhibit the endotoxic activity of isolated LPS and whole bacteria . All three proteins blocked endotoxin activity in: 1) the Limulus amoebocyte lysate assay, 2) priming of PMN for enhanced arachidonate release, and 3) stimulating leukocyte oxidase activity in 1% blood . However, the proteins differ markedly in both relative potency (BPI >> p15s = NP1) in the presence of the plasma LPS-binding protein and in the range of LPS chemotypes that can be inhibited . BPI potently neutralizes LPS of any chemotype, but p15s and defensins are less active against long-chain (S-type) LPS . In whole blood ex vivo, the p15s and NP1 are approximately 1000-fold less potent than BPI, but at subinhibitory doses act in synergy with BPI to inhibit the TNF-inducing activity of a serum-resistant encapsulated strain of Escherichia coli (K1/r) . The anti-endotoxic effects of p15 and NP1 against E . coli K1/r in whole blood appear secondary to growth arrest, because, in marked contrast to BPI, they are not evident against nonviable bacteria (pretreated with antibiotic) nor isolated LPS . Thus, BPI stands out for its ability to inhibit isolated or bacterial LPS under physiologic conditions . However, p15s and defensins may also contribute to suppression of endotoxic signaling by Gram-negative bacteria via synergistic (with BPI) growth inhibition upon extracellular release of these proteins from PMN during inflammation.

Biochem Pharmacol, 1995 May 11, 49(9), 1249 - 54
Cephalosporins are scavengers of hypochlorous acid; Lapenna D et al.; Potential scavenging properties of cephalosporins (i.e . cefamandole, cefotaxime and ceftriaxone) towards hypochlorous acid (HOCl) as well as the antibacterial activity of control and HOCl-reacted antibiotics were investigated . We found that these drugs, at therapeutically relevant concentrations, are indeed scavengers of HOCl, with ceftriaxone showing the highest anti-HOCl capacity . However, the efficiency of cephalosporins in protecting biological molecules is also related to the chemical identity of such molecules . Indeed, the polyenoic compound beta-carotene is much better protected that the thiol compound GSH against HOCl attack . Moreover, the drugs do not appear to form chloramine derivatives as a result of their reaction with HOCl, and they inhibit taurine-chloramine formation . After HOCl challenge, the antibacterial activity of cefamandole, cefotaxime and ceftriaxone (tested against the standard strain Escherichia coli ATCC 25922) is approx . 8-, 5- and 4-fold lower, respectively, than that of the HOCl-unreacted antibiotics . The depression of the antibacterial activity of cephalosporins appears inversely related to their HOCl scavenging capacity, suggesting that the drug antioxidant groups may protect the beta-lactam ring against HOCl attack . In conclusion, physiological biomolecules are protected by cephalosporins against HOCl-driven oxidative injury with varying efficiency, this antioxidant defence being a consequence of a direct drug scavenging capacity towards HOCl . The interaction of cephalosporins with HOCl, however, results in a depression of their antibacterial activity.

Dtsch Med Wochenschr, 1995 May 5, 120(18), 641 - 5
{Gastrointestinal amyloidosis in IgG-chi-light chain plasmacytoma . Diagnostic problems despite advanced changes}; Reithmeier A et al.; A 50-year-old man with an IgG-chi light chain multiple myeloma stage IIIA, developed--in a phase of low disease activity, after 18 months of an uncomplicated course--marked malabsorption syndrome with 20 kg weight loss, diarrhoea and meteorism . Although the H2-breath test indicated intestinal bacterial colonisation, neither antibacterial treatment with trimethoprim/sulphamethoxazole and metronidazole nor prokinetic treatment with cisapride (30 mg daily) and erythromycin (1 g twice daily) improved the symptoms . Suspected amyloidosis was not demonstrable at first, despite repeated step biopsies of stomach, duodenum and rectum . Amyloidosis of the entire gastrointestinal tract was proven only by repeated biopsies deep into the submucosa . Despite treatment of the underlying disease with melphalan and prednisone (Alexanian's scheme) the amyloidosis advanced further to involve liver, spleen, lung, kidneys and heart . The patient died, 2 years after diagnosis of the multiple myeloma, from recurrent pulmonary emboli due to atrial fibrillation.

J Antibiot (Tokyo), 1995 May, 48(5), 399 - 407
Synthesis of novel 6-alpha and 6-beta-alkylcarbonylmethyl substituted penems; Pentassuglia G et al.; 6-alpha and 6-beta Alkylcarbonylmethyl penems were synthesized from 6-alpha-bromo and 6-oxo penicillanates respectively and their in vitro antibacterial activity was studied . The compounds were generally active against Gram-positive but not against Gram-negative strains, the compounds of the 6-beta series being more active . Relatively to imipenem, taken as reference compound, the penems resulted more stable towards chemical hydrolysis in Tris-HCl buffered medium (pH 7.4) but more sensitive towards dehydropeptidase-I (DHP-I).

J Antibiot (Tokyo), 1995 May, 48(5), 363 - 8
AKD-2A, B, C and D, new antibiotics from Streptomyces sp . OCU-42815 . Taxonomy, fermentation, isolation, structure elucidation and biological activity; Akeda Y et al.; An antibiotic complex, AKD-2, was isolated from the mycelial cake of Streptomyces sp . OCU-42815 . The lipophilic substances in this complex were further purified by a recycling HPLC procedure and were designated AKD-2A, C and D . AKD-2B was obtained as a mixture of AKD-2B1 and AKD-2B2 . These substances were identified as monoglycerides having branched chain fatty acids and exhibited both antibacterial and antifungal activities.

Biosci Biotechnol Biochem, 1995 May, 59(5), 876 - 80
Promoinducin, a novel thiopeptide produced by Streptomyces sp . SF2741; Yun BS et al.; Our continued screening to find tipA promoter-inducing substances resulted in the isolation of promoinducin from a mycelial extract of Streptomyces sp . SF2741 . Based on various 1D- and 2D-NMR studies, including field gradient (FG)-COSY, HSQC, FG-HMBC, phase-sensitive 13C-decoupled HMBC and NOESY experiments, promoinducin's structure was established to be a thiopeptide composed of threonine, some unusual amino acids masked at their carboxyl groups by thiazole or methyloxazole rings, sulfomycinamate and five dehydroalanine residues . Promoinducin induced the tipA promoter at 40 ng/ml, and also exhibited strong antibacterial activity against some Gram-positive bacteria.

J Invertebr Pathol, 1995 May, 65(3), 261 - 8
Trypanosoma cruzi and Trypanosoma rangeli: interplay with hemolymph components of Rhodnius prolixus; Mello CB et al.; Studies were carried out on the course of infection of Trypanosoma cruzi (clone Dm28c) and Trypanosoma rangeli (clone San Agustin) and their interactions with hemolymph components of Rhodnius prolixus . These parasites when inoculated into the hemocoel of adult R . prolixus (i) had different courses of infection (T . rangeli had high rates of both multiplication and infection and T . cruzi had no division and disappeared soon from the hemolymph); (ii) induced high but no differential increases in lysozyme levels; (iii) failed to induce any other antibacterial activity; (iv) showed similar patterns of hemolymph agglutination activity for erythrocytes and parasites, although there was evidence of limited, unquantifiable, agglutination of T . cruzi; (v) elicited different hemocyte responses with only the T . rangeli infection resulting in significantly increased hemocyte counts; and (vi) did not induce trypanolytic activity . These experiments, unlike previous studies, also showed (i) an interaction of these trypanosomes with the prophenoloxidase-activating system {phenoloxidase (PO) production was spontaneously activated by both parasites but the number of T . cruzi in the hemolymph was directly correlated with PO levels} and (ii) that the elimination of T . cruzi also corresponded to the formation of nodules in the hemolymph . The significance of these results is discussed in relation to the hypothesis that T . rangeli but not T . cruzi has the ability to escape from and perhaps utilize the vector immune system in order to successfully colonize the R . prolixus hemolymph.

J Invertebr Pathol, 1995 May, 65(3), 217 - 24
PCBs increase molecular-related activities (lysozyme, antibacterial, hemolysis, proteases) but inhibit macrophage-related functions (phagocytosis, wound healing) in earthworms; Ville P et al.; Both humoral and cellular immunodefense responses of the earthworms, Eisenia fetida andrei, Eisenia hortensis, and Lumbricus terrestris, have been compared after exposure to the PCB Aroclor 1254 . Responses mediated by free factors, detected by in vitro assays for lysozyme, hemolysis, and proteases, were increased in both Eisenia . Antibacterial activity directed against pathogenic bacteria was increased in E.f . andrei . The resistance of L . terrestris against non-pathogenic bacteria was decreased, confirming that the bacteria were treated by different systems according to their pathogenicity . Nonspecific cellular functions, including phagocytosis and those related to wound healing, decreased dramatically in all earthworms.

Am J Gastroenterol, 1995 May, 90(5), 815 - 8
Double pylorus: report of a longitudinal follow-up in two refractory cases with underlying diseases; Hu TH et al.; Double pylorus is either a congenital abnormality or an acquired complication of peptic ulcer disease . We had followed two patients for 3 and 5 yr, respectively, to observe the processes of formation and the prognosis of double pylorus . Initially, duodenal ulcer was found in one patient with diabetes mellitus and chronic renal failure, and gastric ulcer was found in the other with chronic obstructive pulmonary disease . Both developed double pylorus with refractory courses . In spite of intensive medical treatment, both of them had persistent ulcers in the fistulous tract and failed to develop reepithelization . Helicobacter pylori was found in all of the specimens of gastroduodenal biopsies in both cases . Therefore, we believe that the refractory courses of double pylorus may be related to the underlying diseases and/or the presence of H . pylori . Antibacterial treatment of H . pylori or surgical intervention should be considered for patients with this condition.

Exp Parasitol, 1995 May, 80(3), 401 - 6
Brugia pahangi: the effects of cecropins on microfilariae in vitro and in Aedes aegypti; Chalk R et al.; Synthetic cecropins, antibacterial peptides from insect haemolymph, have been tested for their ability to attenuate the motility of microfilariae of the filarial nematode Brugia pahangi in an in vitro assay . Fifty micromolar concentrations of these peptides, equivalent to physiological concentrations in immune-stimulated insects, cause significant attenuation of motility compared with untreated microfilariae . Similar results were obtained with cecropins A and B . This is the lowest concentration for which cecropin has been reported to be active against eukaryote organisms . Antiserum to the cecropin homologue sarcotoxin 1A successfully blocked the observed activity . When the same concentration of cecropin B was coinjected with B . pahangi microfilariae into adult females of the mosquito, Aedes aegypti, a significant reduction in the numbers of developing larvae was observed.

Arkh Patol, 1995 May-Jun, 57(3), 75 - 6
{Evaluation of contamination of the gastric mucosa with Helicobacter pylori and activity of chronic gastritis}; Aruin LI et al.; An objective method of histological evaluation of stomach mucosa contamination with H . pylori proposed by the authors comprises contamination index, contamination density, adhesion density, adhesion index . The response to antibacterial therapy and other factors can also be determined . Chronic gastritis activity is characterized by the activity in surface area, in pits and in lamina propria . The method is simple, reproducible, time-effective, convenient both for diagnosis of chronic H . pylori gastritis and follow-up of the treatment results.

Epidemiol Mikrobiol Imunol, 1995 May, 44(2), 84 - 90
{Transposons coding beta-lactamase with an extended spectrum of effects and resistance to other antibiotics}; Babalova M et al.; The authors present contemporary knowledge concerning the transposition of resistance genes to penicillins, cephalosporins and carbapenems, and transposons and integrins coding resistance to other antibacterial substances . Transposition is, together with bacterial conjugation and transduction with bacteriophages, another mechanism of mobility and restructuring of resistance genes in bacterial strains of the same and also in other bacteria.

Bone Marrow Transplant, 1995 May, 15(5), 803 - 4
Recovery from rhabdomyolysis after allogeneic BMT: report of a case with speculation on causation; Jackson SR et al.; A case of fulminant rhabdomyolysis occurring 4 months after allogeneic BMT for CML is reported . The patient developed rhabdomyolysis following the empiric institution of antibacterial and anti-tuberculous medication . His inpatient course was complicated by the development of acute anuric renal failure and a severe myopathy . With aggressive supportive care, both of these complications resolved, making this patient the only reported survivor of rhabdomyolysis occurring after BMTPublication Types:

Case Reports

What Is Staphylococcus Aureus?, What Is Listeria Monocytogenes?, What Is Biofilm?, What Is Environmental Microbiology?, What Is Botulism?, e, Bacterium, r, Microbe, e, Bacteria, o, Microorganisms, a, Bacteriology, o, Microorganism, e, Yeasts, c, Escherichia coli, r, Salmonella, c, Enterobacters, i, Escherichia coli, i, Escherichia coli, n, Functional genomics, c, Cryptococci, n, Streptomycin, s, Antibiotics, a, Pseudomonas, i, Microbial, o, Streptococcal, s, Sepsis, s, Escherichia coli, c, Functional genomics, a, Escherichia coli, s, Prokaryotes, n, Multidrug resistant, c, Schizosaccharomyces

Scientific Publications - Work Done by Microbiology Reader Bioscreen C
Agricultural Microbiology Anaerobic Microbiology Antimicrobial Susceptibility Artificial Atmosphere Bioassay of Antibiotics Biofilm Microbiology Bioreactor Technology Biotechnology Cell Biology Clinical Microbiology Environmental Microbiology Experiments with Yeast	Fermentation Food Microbiology Functional Genomics Gene Technology Growth Media Development Growth Rate and Lag Time Industrial Microbiology Medical/Pharmaceutical Field Microbiological Assay Microbiological Research Microbiology of Cosmetics go to a specific theme...	Military Microbiology Molecular Microbiology Mutagenicity and Genotoxicity Oral Microbiology Patents Postantibiotic Studies Soil Microbiology Spore Microbiology Veterinary Microbiology Waste/Wastewater Treatment Water Microbiology Wine Microbiology

� 2005 Transgalactic Ltd (manufacturer of Bioscreen C software) | Privacy Statement | P.O. Box 1393, 00101 Helsinki, Finland, phone: +358 9 85172920, fax: +358 9 8749481, e-mail: microbiology@bionewsonline.com

Last modified: May 25, 2005