Bactericidal

Zentralbl Bakteriol, 1994 Jun, 281(1), 80 - 4
Antibacterial efficacy of ciprofloxacin in a case of endocarditis due to Cardiobacterium hominis; Vogt K et al.; Endocarditis due to Cardiobacterium hominis is rare and may be treated with a variety of antibiotics . We isolated the bacteria from blood cultures of a patient with Cardiobacterium hominis endocarditis who could be successfully treated with ciprofloxacin . The bacterial features of Cardiobacterium hominis are presented, and susceptibility to ciprofloxacin is documented with bacterial killing curves employing peak and trough specimens of patient's serum.

Afr J Med Med Sci, 1994 Jun, 23(2), 143 - 6
The effect of antibacterial agents on plasma vitamin C levels; Alabi ZO et al.; Previous report on the estimation of plasma ascorbic acid levels in patients with chronic osteomyelitis indicated that the plasma ascorbic acid level is reduced in patients on antibiotics . The plasma study of the effects of anti-bacterial agents on plasma ascorbic acid in vitro, was carried out to substantiate the hypothesis than these agents lower plasma ascorbic acid levels . Increasing amounts of each of seven anti-bacterial agents: ampicillin, chloramphenicol, cefotaxime, gentamycin, benzyl and procaine penicillin combination (seclopen), co-trimoxazole, and streptomycin significantly (P < 0.01, r = -0.9587) reduced plasma vitamin C levels in vitro . There was moderate but insignificant reduction in plasma vitamin C levels with clindamycin (r = -0.799) . The reduction of the plasma vitamin C levels observed in the presence of the eighth anti-bacterial agent, clindamycin, lacked significance (r = -0.799) . The cause of this reduction of plasma vitamin C levels by anti-bacterial agents in vitro is not yet understood . A supplement of vitamin C may be required in patients on anti-bacterial agents.

Biochem Biophys Res Commun, 1994 May 30, 201(1), 228 - 34
Identification of a new class of ETA selective endothelin antagonists by pharmacophore directed screening; Chan MF et al.; Novel endothelin antagonists were identified through a "pharmacophore directed screening" strategy . The sulfanilamide antibacterial agent sulfisoxazole was found to be a good endothelin receptor antagonist (IC50's of 0.60 microM and 22 microM for the ETA and ETB receptors, respectively) . The structurally similar sulfamethoxazole was found to be a weaker antagonist (IC50 for ETA 16 microM and for ETB 230 microM) . These compounds represent a new class of low molecular weight and ETA-selective non-peptide endothelin antagonists.

J Chromatogr A, 1994 May 6, 668(1), 241 - 7
Interactions between fluoroquinolones, Mg2+, DNA and DNA gyrase, studied by phase partitioning in an aqueous two-phase system and by affinity chromatography; Khac SB et al.; The primary target of fluoroquinolones has been identified as the enzyme DNA gyrase, but the mechanism of action of these antibacterial agents is still a matter of controversy . Using partitioning in aqueous polyethylene glycol (PEG)-dextran systems, the affinities of several fluoroquinolones for DNA were determined with accuracy and at equilibrium . It was proved that the binding was strongly dependent on the ability of the drugs to bind Mg2+, with KA values of about 40 000 l mol-1, but was poorly related to the antibacterial activity {minimal inhibitory concentration (MIC) and gyrase inhibition} . Using affinity chromatography on immobilized fluoroquinolone, it was shown that DNA gyrase was unable to bind fluoroquinolones in the absence of DNA, but that a DNA-quinolone-gyrase complex was formed in the presence of Mg2+.

Br J Dermatol, 1994 May, 130(5), 569 - 75
Anti-inflammatory actions of benzoyl peroxide: effects on the generation of reactive oxygen species by leucocytes and the activity of protein kinase C and calmodulin; Hegemann L et al.; For many years, benzoyl peroxide has been used as a topical treatment for acne . Although the drug has been shown to interfere with a variety of pathways, believed to be of importance in the aetiopathogenesis of acne, its mechanism of action is thought to be principally antibacterial . Recent circumstantial evidence suggests that protein kinase C might serve as an additional pharmacological target of benzoyl peroxide . In the present study, we investigated the effects of benzoyl peroxide on the release of reactive oxygen species, regulated by protein kinase C and calmodulin, from human neutrophils, a potentially important step in acne inflammation . Micromolar drug concentrations were found to inhibit the release of reactive oxygen species, but there was marked drug-induced cytotoxicity in neutrophils . However, when tested in cell-free assays, benzoyl peroxide displayed marginal inhibition of protein kinase C, but failed to antagonize calmodulin . Further investigations on its mechanism of action revealed non-specific interference with nucleotide binding sites . Therefore, the data presented here indicate that, in contrast with our previous findings with tetracycline derivatives, the clinical anti-inflammatory activity of benzoyl peroxide is unlikely to be mediated by protein kinase C or calmodulin . The differential interaction of drugs with protein kinase C and calmodulin might help to explain their different clinical usefulness in various degrees of acne severity.

Gut, 1994 May, 35(5), 701 - 4
Healing of protein losing hypertrophic gastropathy by eradication of Helicobacter pylori--is Helicobacter pylori a pathogenic factor in Ménétrier's disease?
Bayerdorffer E, Ritter MM, Hatz R, Brooks W, Ruckdeschel G, Stolte M.
Hypertrophic gastropathy--that is, Menetrier's disease--was found, in a retrospective analysis, to be associated with Helicobacter pylori in more than 90% of patients . It is proposed that hypertrophic gastropathy represents a special form of H pylori gastritis in these patients . A case is described of a 28 year old woman with Menetrier's disease associated with proved protein loss from the stomach . Treatment with cimetidine for more than three years had little benefit when colonisation by H pylori was detected . Density of H pylori colonisation and activity of gastritis, which was also present in the first biopsy specimens taken five years ago, were more pronounced in the body than in the antrum, which is in agreement with the characteristics of H pylori gastritis found in other cases with Menetrier's disease . A 14 day antibacterial treatment course with 750 mg amoxicillin three times a day combined with 40 mg omeprazole three times a day was started in April 1991 . This resulted in eradication of H pylori and the return to normal of giant folds and the mucosal histology . Serum protein concentrations returned to normal within six weeks and remained normal at two endoscopies during a two year follow up . This case report suggests that a subgroup of the patients with Menetrier's disease may be healed by the eradication of H pylori.

Laryngoscope, 1994 May, 104(5 Pt 1), 631 - 7
Reduction of streptomycin-induced acute and chronic toxicities; Doretto MC et al.; The acute and chronic toxicities of streptomycin sulfate (SS) and of the streptomycin hydrochloride-calcium chloride complex (SCC) were compared . The LD50 determined in mice was significantly higher for SCC than for SS . Chronic toxicity was evaluated by recording the nystagmus induced by damped torsion pendulum in rabbits . SS and SCC treatments (200 mg/kg intramuscularly of absolute streptomycin base) decreased the duration, the maximal frequency, and the total number of beats of nystagmus . However, SCC-induced changes were significantly lower than SS-induced ones . The extent of the lesion in the crista ampullaris was evaluated by light and electron microscopy and was correlated with the electrophysiological findings . Because the authors also demonstrated that there are no differences in the antibacterial effects of these salts, SCC may have a place in long-term streptomycin treatment.

J Pharmacol Exp Ther, 1994 May, 269(2), 496 - 502
Active intestinal secretion of the fluoroquinolone antibacterials ciprofloxacin, norfloxacin and pefloxacin; a common secretory pathway?
Griffiths NM, Hirst BH, Simmons NL.
The transepithelial transport of three fluoroquinolones, norfloxacin, ciprofloxacin and pefloxacin has been compared by using cultured human intestinal Caco-2 cell-layers . Absorptive (apical-basal) fluxes of ciprofloxacin and norfloxacin are small relative to basal to apical fluxes . Norfloxacin and ciprofloxacin are thus subject to active transepithelial secretion . Active net secretion of norfloxacin displays saturation kinetics with Vmax and Km values of 36.2 +/- 6.9 nmol.cm-2.hr-1 and 1.42 +/- 0.79 mM . In contrast, transepithelial pefloxacin fluxes are large, show marked saturation while the direction of net flux is variable and small relative to transepithelial fluxes . Norfloxacin, pefloxacin and ciprofloxacin are all subject to accumulative transport across the basal surface of Caco-2 cell layers . A number of 4-quinolones and fluoroquinolones are capable of inhibition of both net secretion of ciprofloxacin and cellular accumulation across the basal-lateral cell surface . Cinoxacin, a 4-quinolone may selectively inhibit exit from the cell across the apical membrane . Cross-competition studies suggest that fluoroquinolones may compete for a common carrier at the basal-lateral membrane . It is likely that the mechanism of transepithelial secretion involves a common accumulative transport at the basal-lateral membrane followed by facilitated exist across the apical membrane . Pefloxacin may interact with a brush-border carrier for which norfloxacin and ciprofloxacin are poor substrates, enhancing the absorptive flux of this fluoroquinolone.

Urology, 1994 May, 43(5), 714 - 8
Vesicoureteric reflux and videourodynamic studies: results of a prospective study after three years of follow-up; Scholtmeijer RJ et al.; OBJECTIVE . To study prospectively the influence of videourodynamic studies on the management of children with vesicoureteric reflux . METHODS . One hundred one children with reflux were investigated routinely with videourodynamic studies, as well as renal scans, ultrasound studies, and/or intravenous urograms . The studies were repeated at one, three, and five years . If bladder instability was demonstrated, the primary treatment consisted of anticholinergic drugs and antibiotics, regardless of the grade of reflux . In reflux Grades IV and V with instability and renal scars, surgery was performed . In case of a stable bladder, reflux Grades I-III received antibacterial treatment, while surgical correction was used for reflux Grades IV and V . RESULTS . The results of three years of follow-up of 101 children are reported . Bladder instability was found in 39 children . Thirty of them with reflux Grades I-IV and instability could be managed with anticholinergic and antibacterial drugs, while 9 needed surgical correction . CONCLUSIONS . A voiding cystourethrogram is only sufficient for the detection of reflux but for correct management of these children a (video)urodynamic study is mandatory . After treatment of frequently found bladder dysfunction, the reflux will disappear in the majority of cases.

J Antimicrob Chemother, 1994 May, 33(5), 999 - 1004
Bactericidal effect of gentamicin trough concentration provides a rationale for administration of bolus doses and maintenance of trough levels; McLean AJ et al.; An in-vitro study was made of the influence of trough gentamicin concentrations (Cmin) on the bactericidal effect of gentamicin against Escherichia coli NCTC 10418 . Lag phase bacterial cells were exposed in vitro to gentamicin concentration versus time profiles which modelled profiles in patients up to 30 min after either an 80 mg iv bolus over 1 min or a 30 min infusion . The gentamicin was removed 30 min post-dose and the cultures were reconstituted in broth containing a constant trough gentamicin concentration in the range of 0-3 mg/L . Bacterial cfu counts and gentamicin concentrations were measured before and during antibiotic exposure . It was found that antibacterial activity was not determined by AUC, but rather there was a threshold trough concentration producing a bactericidal effect which differed between bolus and infusion profiles . With the bolus profile trough concentrations required for a bactericidal effect were 0.5-1.0 mg/L, while with the infusion profile generating an identical post-distribution peak concentration, trough concentrations required for a sustained bactericidal effect were 2.5-3.0 mg/L . These findings favour bolus iv gentamicin dosing over infusion dosing, provided appropriate attention is paid to any potential toxicity associated with high peak concentrations . Trough data indicate the likely need to maintain critical trough concentrations by choice of appropriate intervals between doses.

Chem Pharm Bull (Tokyo), 1994 May, 42(5), 1088 - 95
Structure-activity relationship study of 6-O-methylerythromycin 9-O-substituted oxime derivatives; Kawashima Y et al.; In order to develop new-generation macrolide antibiotics active against erythromycin (EM)-resistant strains, a series of 6-O-methyl EM 9-O-substituted oxime derivatives was synthesized and evaluated for antibacterial activity against EM-resistant (S . aureus J-109) and susceptible (S . aureus 209P) strains . To understand how substituents affect the biological activity, the quantitative structure-activity relationships (QSAR) was analyzed using the Hansch-Fujita method . With the EM-resistant strain, the positive coefficient for log P may indicate that higher hydrophobicity of molecules is favorable for antibacterial activity . The negative coefficients of the Sterimol parameters L, B1, and B5 may indicate that long, bulky substituents are unfavorable . With the EM-susceptible strain, the negative coefficient for log P may indicate that hydrophilicity is important for antibacterial activity . A short substituent is also required to improve the activity . Based on the QSAR model, a derivative (87) having an anthracenylmethyl moiety was synthesized to reinforce and confirm the correlation . The activity of 87 against the EM-resistant strain was significant . In QSARs of 6-O-methyl EM-A 9-O-substituted oxime derivatives, the difference of the contribution of log P to the antibacterial activity between EM-resistant and susceptible strains was clearly recognized.

Ophthalmic Surg, 1994 May, 25(5), 303 - 6
Retinal toxicity of intravitreally injected faeriefungin; Dunlap WA et al.; Faeriefungin is a new antibacterial and antifungal agent derived from a strain of Streptomyces griseus var . autotrophicus . Under anesthesia, 12 albino rabbits underwent injection in their right eyes with 400, 200, 100, 40, 20, and 10 micrograms of faeriefungin . Retinal toxicity was assessed by electroretinography and light and transmission electron microscopy . Injection of 400 micrograms resulted in severe retinal toxicity, although indirect ophthalmoscopy was unremarkable . At 200 micrograms, there was moderate toxicity . Intravitreal injection of concentrations of 100 micrograms or less produced no neuroretinal toxicity . These data suggest that faeriefungin is a potentially useful drug in the treatment of fungal or bacterial endophthalmitis.

J Burn Care Rehabil, 1994 May-Jun, 15(3), 213 - 23
A review of the dosimetry of 1% silver sulfadiazine cream in burn wound treatment; Fuller FW et al.; A review of the periodical literature relating to burn topical antibacterial agents as listed in the Cumulated Index Medicus from January 1, 1965, through November 30, 1992, as well as bound volumes and unpublished material reveals that the optimal dose and mode of deployment of 1% silver sulfadiazine cream in burn wound therapy have not been fully defined . Defining these should provide better control of sepsis in burn facilities . The effectiveness of a burn topical antibacterial agent depends in part upon the extent to which it is absorbed . The process of absorption of a burn topical antibacterial agent may be likened to that of an in vitro model in which the absorption of a test solute through an isolated preparation of the stratum corneum is determined in a diffusion cell . Some of the determinants are the concentration of the solute, the volume of the solvent, the duration of contact with the membrane, the binding tendency of the solute to the membrane, the integrity and wetness of the membrane, intrinsic factors of the solute/membrane interaction (distribution and diffusion coefficients), and the adjuvant formulation . Three of these (solvent volume, duration of solute contact, and membrane wetness) are readily adjusted . As a possible preliminary to the more effective clinical use of 1% silver sulfadiazine, a ranging of these three factors and of the silver sulfadiazine concentration, should be carried out in a rat model with septic burns . Though control of burn wound bacteria remains of overriding importance, the absorption of silver through the burn wound treated with silver sulfadiazine, binding to normal tissues, is a source of rising concern and requires further investigation.

Zhongguo Zhong Yao Za Zhi, 1994 May, 19(5), 297 - 8, inside backcover
{Active constituents of Commelina communis L.}; Tang XY et al.; According to the pharmacological results five compounds were isolated from the herb of Commelina communis . Based on physico-chemical constants and spectral data, four of them were identified as n-triacontanol, p-hydroxycinnamic acid, daucosteril and D-mannitol . p-hydroxycinnamic acid shows antibacterial activity and D-mannitol shows antitussive effect.

Med Tekh, 1994 May-Jun, (3), 38 - 40
{Utilization of the new synthetic dissolving sutures caproag in obstetrics and gynecology}; Krasnopolskii VI et al.; The paper deals with the experience with synthetic resolving Caproag suture threads which have antibacterial properties for suturing the uterine section during Caesarean and other gynecological operations . There is evidence for its high efficacy in optimal tissue regeneration . Caproag was used in the most life-threatening infectious and septic complications . With this, a reduction has been achieved in the incidence of postoperative pyo-inflammatory diseases, which makes Caproag compare favourably with the conventional suture threads catgut and vicryl.

Antibiot Khimioter, 1994 May, 39(5), 52 - 65
{New achievements in the fluoroquinolone problem: possibilities of increasing activity and expansion of the spectrum of action}; Padeiskaia EN; Studies of antibacterial compounds and drugs belonging to the derivatives of 6-fluoroquinolones are reviewed . The structure-function dependencies, the introduction of additional fluorine atoms to the structure and the cycle substitutions at positions 5 and 8 are discussed from the viewpoint of the antibacterial activity increasing and the spectrum broadening . The data on the activity of new 6-fluoroquinolones against gram positive bacteria, including pneumococci, anaerobic organisms, mycobacteria, chlamydia, and mycoplasma are presented . Compounds belonging to 6-fluoroquinolones substituted at positions 2 and 3 are discussed . The activity of 6-fluoroquinolones and their nonfluorinated derivatives is compared in general.

Lik Sprava, 1994 May-Jun, (5-6), 43 - 5
{Antigen-binding lymphocytes in pulmonary tuberculosis patients with the side effects of antitubercular preparations}; Fedoruk NI; 70 patients with pulmonary tuberculosis, experiencing side-effects associated with antibacterial preparations were examined as were 30 patients receiving similar therapy with no complications being developed, and 20 apparently healthy subjects . It was established that the level of antigen-binding lymphocytes depends on the extent of sensitization to the allergen in question and reaches the highest values in patients presenting with adverse reactions . Preliminary treatment of lymphocytes with a medicamentous preparation results in some reduction of the number of antigen-binding lymphocytes . Values for the index of restoration of stimulated expression of the receptors to the medicinal preparations by trypsinized lymphocytes are higher in patients experiencing adverse reactions than they are in patients with pulmonary tuberculosis, presenting with no ill-effects, and in donors.

Biosci Biotechnol Biochem, 1994 May, 58(5), 826 - 9
Syntheses and antibacterial activities of gramicidin S analogs containing L-ornithine in place of L-valine; Soejima Y et al.; A gramicidin S analog ({Orn1,1'}GS.4HCl) containing L-ornithine in place of L-valine at the 1,1' positions was synthesized by the conventional solution method in order to examine whether this analog had antibacterial activity toward Gram-negative bacteria . In the synthesis of {Orn1,1'}GS.4HCl, two intermediate analogs ({Orn1,1', Orn(For)2,2'}GS.2HCl and {Orn(Z)1,1'}GS.2HCl) were obtained . {Orn1,1'}GS.4HCl and {Orn1,1', Orn(For)2,2'}GS.2HCl showed no activity toward either Gram-negative or Gram-positive bacteria, whereas {Orn(Z)1,1'}GS.2HCl showed appreciable activity toward only Gram-positive bacteria.

Ann N Y Acad Sci, 1994 Apr 15, 712, 117 - 30
Regulation of antibacterial protein synthesis following infection and during metamorphosis of Manduca sexta; Dunn PE et al.; Larvae of the tobacco hornworm, Manduca sexta, respond to intrahemocoelic injection of bacteria or bacterial cell wall peptidoglycan with induced synthesis of a suite of antibacterial proteins . Previous studies have demonstrated peptidoglycan regulation of the synthesis of these antibacterial proteins . In addition to eliciting enhanced synthesis of antibacterial proteins, peptidoglycan fragments also elicit a "malaise syndrome" characterized by decreased feeding and growth, delayed metamorphosis, and altered excretion . We speculate that these symptoms may be components of a mechanism to flush out and sterilize the midgut lumen, one of the primary sources of bacterial infection in insects . Studies of naive larvae have demonstrated the accumulation of lysozyme in the differentiating pupal midgut epithelium and release of lysozyme into the pupal midgut lumen after the larval midgut epithelium has been sloughed off . These observations have been extended by the identification of potent bactericidal activity against E . coli and immunoreactive hemolin, together with lysozyme, in the lumen of the newly differentiated pupal midgut.

Cancer, 1994 Apr 15, 73(8), 2099 - 106
Antifungal prophylaxis during remission induction therapy for acute leukemia fluconazole versus intravenous amphotericin B; Bodey GP et al.; BACKGROUND . Fungal infection is a frequent and often fatal complication in patients undergoing remission induction therapy for acute leukemia . Although candidiasis is the most common infection, mold infections are increasing in frequency . Fluconazole (FLU) is a new antifungal agent that has been used successfully to treat Candida infections and has modest activity against aspergillosis in animal models . Subtherapeutic doses of amphotericin B (AMB) have been considered effective as prophylaxis in these patients . This study was designed to compare the efficacy and toxicity of these agents as antifungal prophylaxis . METHODS . Adults with acute leukemia undergoing remission induction chemotherapy randomly were assigned to receive antifungal prophylaxis with AMB (0.5 mg/kg three times weekly) or FLU (400 mg daily) . Trimethoprim-sulfamethoxazole was administered as an antibacterial prophylaxis . Prophylaxis was continued until the patient achieved complete remission or was treated for 8 weeks without antileukemic response . Prophylaxis was discontinued if the patient experienced a possible or proven fungal infection or a serious toxicity . RESULTS . Overall, 58% of the 36 patients assigned to AMB successfully completed prophylaxis compared with 80% of the 41 patients assigned to FLU (< 0.05) . Proven, probable, or possible fungal infections occurred in 31% and 17% of the patients, respectively . The risk of discontinuing prophylaxis due to fungal infection or toxicity increased with time in the study and was significantly greater for AMB (P = 0.02) . CONCLUSIONS . At the dose used in this study, AMB was no more effective and was more toxic than FLU for prophylaxis of fungal infections in patients undergoing remission induction chemotherapy for acute leukemia.

Biochemistry, 1994 Apr 12, 33(14), 4237 - 44
Equilibrium folding studies of tetrameric R67 dihydrofolate reductase; Zhuang P et al.; R67 dihydrofolate reductase (DHFR) is an R-plasmid encoded enzyme that confers resistance to the antibacterial drug trimethoprim . This enzyme is not homologous in sequence or structure to chromosomal DHFRs . Equilibrium folding of tetrameric R67 DHFR was studied and found to be fully reversible . Formation of an inactive intermediate was assayed by loss of enzyme activity . Denaturation of the intermediate was monitored by concurrent changes in fluorescence and circular dichroism signals . Both transitions are protein concentration dependent . A simple model fitting these data is tetramer<==>2 dimers<==>4 unfolded monomers . No evidence for folded monomer was found . Global fitting of all the folding data yielded a delta GH2O of -9.63 kcal/mol for the initial transition and a delta GH2O of -12.35 kcal/mol for the second transition . In addition, thermal unfolding of tetrameric R67 DHFR was found to be reversible A folding intermediate also occurred during thermal unfolding as evidenced by the asymmetric endotherms and a delta Hcalorimetric/delta H(van't Hoff) ratio of 2.1.

FEBS Lett, 1994 Apr 4, 342(2), 189 - 92
Synthesis and characterization of sapecin and sapecin B; Kim JI et al.; Two insect defencins, sapecin and sapecin B, were chemically synthesized to confirm their structure and antibacterial activity and also to examine the possibility that these peptides bind to the same site on the large conductance calcium-activated potassium channel as charybdotoxin . Both synthetic peptides showed the same antibacterial activity as native sapecins, indicating that the synthetic peptides folded correctly in the chemical synthesis . Synthetic sapecins did not show an inhibitory effect on {125I}charybdotoxin binding to rat brain synaptic membranes, suggesting that sapecin B recognizes a different binding site from that of charybdotoxin despite the similar structural motif.

J Antibiot (Tokyo), 1994 Apr, 47(4), 466 - 76
Synthesis and structure-activity relationships of 7 beta-{(Z)-2-(2- aminothiazol-4-yl)-3-(substituted)-2-propenoylamino}-3-cephems with C-3 substitutions; Ishikura K et al.; Synthesis and biological activity of a series of 7 beta-{(Z)-2-(2- aminothiazol-4-yl)-3-(substituted)-2-propenoylamino}-3-cephe m-4-carboxylic acids with C-3 substitutions and their pivaloyloxymethyl esters are described . These acid compounds exhibited potent antibacterial activity against both Gram-positive and Gram-negative bacteria . Pivaloyloxymethyl esters of selected compounds in this series were found to be well absorbed from small intestine in mice . Pivaloyloxymethyl 7 beta-{(Z)-2-(2-aminothiazol-4-yl)-2-pentenoylamino}-3- carbamoyloxymethyl-3-cephem-4-carboxylase hydrochloride hydrate (S-1108) was finally selected as the candidate for clinical evaluation.

J Antibiot (Tokyo), 1994 Apr, 47(4), 453 - 65
Synthesis and structure-activity relationships of 7 beta-{(Z)-2-(2- aminothiazol-4-yl)-3-(substituted)-2-propenoyl-amino}-3- desacetoxymethylcephalosporins; Ishikura K et al.; Synthesis and biological activity of a series of 7 beta-{(Z)-2-(2- aminothiazol-4-yl)-3-(substituted)-2-propenoylamino}-3-cephe m-4-carboxylic acids and their pivaloyloxymethyl esters are described . These acid compounds exhibited potent antibacterial activity against both Gram-positive and Gram-negative bacteria . Pivaloyloxymethyl esters of selected compounds in this series were found to be well absorbed from small intestine in mice.

Eur J Biochem, 1994 Apr 1, 221(1), 201 - 9
Characterization and transcriptional profiles of a Drosophila gene encoding an insect defensin . A study in insect immunity; Dimarcq JL et al.; Insect defensins are a family of 4-kDa, cationic, inducible antibacterial peptides which bear six cysteine residues engaged in three intramolecular disulfide bridges . They owe their name to certain sequence similarities with defensins from mammalian neutrophiles and macrophages . We report the characterization of a novel defensin isoform from Drosophila and the cloning of the gene encoding a preprodefensin . The gene, which is intronless and present in a single copy/haploid genome, maps at position 46CD on the right arm of the second chromosome . The analysis of the upstream region of the gene reveals the presence of multiple putative cis-regulatory sequences similar to mammalian regulatory motifs of acute-phase-response genes . Transcriptional profiles indicate that the Drosophila defensin gene is induced by bacterial challenge with acute-phase kinetics . It is also expressed in the absence of immune challenge during metamorphosis . These and other data on the Drosophila defensin gene lead us to suggest that insect and mammalian defensins have evolved independently.

Epidemiol Infect, 1994 Apr, 112(2), 367 - 73
Host-microflora interaction in systemic lupus erythematosus (SLE): colonization resistance of the indigenous bacteria of the intestinal tract; Apperloo-Renkema HZ et al.; Experimental data suggest a role for the microflora in Systemic Lupus Erythematosus (SLE) . Anti-ds-DNA antibodies may be pathogenic in SLE by forming immune complexes with DNA . Foreign bacteria in the intestines could constitute the stimulus for anti-ds-DNA antibody production in SLE . Colonization Resistance (CR) is the defence capacity of the indigenous microflora against colonization of the intestines by foreign bacteria . A low CR implies increase of translocation of bacteria and a higher chance of subsequent, possibly DNA-cross-reacting antibacterial antibody production . We measured CR by a comprehensive biotyping technique in healthy individuals and patients with inactive and active SLE . CR tended to be lower in active SLE patients than in healthy individuals (P = 0.09, Wilcoxon one sided, with correction for ties) . This could indicate that in SLE more and different bacteria translocate across the gut wall due to a lower CR . Some of these may serve as polyclonal B cell activators or as antigens cross-reacting with DNA.

Infect Immun, 1994 Apr, 62(4), 1421 - 6
Characterization of a rabbit cationic protein (CAP18) with lipopolysaccharide-inhibitory activity; Hirata M et al.; Cationic antibacterial proteins (CAP) were purified from rabbit granulocytes, and the effects of CAP on lipopolysaccharide (LPS)-induced tissue factor generation by murine peritoneal macrophages and human blood monocytes were studied . CAP were purified from rabbit peritoneal leukocytes by using as an assay the agglutination of erythrocytes coated with Re-LPS . Two proteins with CAP activity, CAP18 (18 kDa) and CAP7 (7 kDa), were isolated by acid extraction, ethanol precipitation, affinity chromatography, gel filtration, and reverse-phase high-pressure liquid chromatography . On the basis of protein sequencing, CAP7 was identified as the C-terminal fragment of CAP18, designated CAP18(106-142) . Various forms of LPS (S-LPS, Re-LPS, and lipid A) activate murine macrophages and human blood monocytes to generate tissue factor (tissue thromboplastin) . Incubation of LPS for 18 h with partially purified CAP (heparin-Sepharose fraction) inhibited the capacity of LPS to induce tissue factor; however, purified CAP18 inhibited about 75% of the activity of S-LPS after 1 h of incubation . CAP more effectively inhibited S-LPS than Re-LPS or lipid A . Synthetic CAP18(106-142) inhibited LPS-induced tissue factor generation by murine macrophages . CAP18(106-142) has greater LPS-binding and LPS-neutralizing activities than CAP18 . We hypothesize that CAP18 and the derivative peptide, CAP18(106-142), bind to LPS and alter the capacity of LPS to initiate disseminated intravascular coagulation . In this regard, CAP may have therapeutic potential for sepsis and endotoxin shock.

Pharmacol Toxicol, 1994 Apr-May, 74(4-5), 240 - 3
UV-dependent quinolone-induced human erythrocyte membrane lipid peroxidation: studies on the phototoxicity of Y-26611, a new quinolone derivative; Wada K et al.; Quinolone antibacterial drugs are widely used as oral therapeutic agents . However, in some patients they cause ultraviolet (UV)-dependent dermatitis . Using lipid peroxidation as an index of phototoxicity, we studied the effects of a new quinolone derivative, Y-26611 together with ofloxacin, sparofloxicin and lomefloxacin on washed human erythrocyte suspensions . Irradiation of erythrocytes with UV-A or UV-B for 60 min . in the presence of Y-26611 (30-600 micrograms/ml) strong dose dependent lipid peroxidation, up to 17.01 nmoles/ml was induced . Under identical conditions, lipid peroxidation induced by up to 600 micrograms/ml ofloxacin, sparofloxacin or lomefloxacin were 0.94, 3.36 and 2.98 nmoles/ml respectively . The lipid peroxidation was entirely dependent on both UV as well as the drug . The lipid peroxidation responses to drug+UV could completely be inhibited by sodium azide (hydroxyl radical, HO . and single oxygen, 1O2 scavenger) or by phenyl N-tert-butylnitrone (PBN, HO . and superoxide anion radical, O2- scavenger) . It is likely that reactive oxygen species generated by interaction between UV-sensitized drug molecules and oxygen molecules mediate erythrocyte membrane lipid peroxidation . The method used in this study is rapid and convenient for screening drugs for UV-dependent cytotoxicity.

J Chemother, 1994 Apr, 6(2), 117 - 20
Study on the bactericidal activity and synergistic effect of neutropenic rat serum with gentamicin; Pea F et al.; It is well known that normal rat serum (NRS) shows an antibacterial activity because of the presence of endogenous substances that are able to express a defence against pathogenic microorganisms . Moreover, in former studies, we observed that NRS presents a synergistic activity with some antibiotics (thus able to lower minimum inhibitory concentration values) . The aim of this research was to study the antibacterial activity and synergistic effect of neutropenic rat sera (NPRS) with gentamicin . The animals were made neutropenic by the i.p . injection of cyclophosphamide (100 mg/kg on day 0 and 75 mg on day 4) . At all tested concentrations (from 0.25% to 5%) NPRS showed lower antibacterial activity than NRS with differences which were always statistically significant . The synergistic activity of NPRS with gentamicin was still present and quite similar to that of NRS, in spite of many altered blood parameters showing evident immunodepression . Some possible interpretations of these results are discussed.

Leuk Lymphoma, 1994 Apr, 13(3-4), 203 - 14
Infections in chronic lymphocytic leukemia: risk factors, and impact on survival, and treatment; Molica S; Patients with chronic lymphocytic leukemia (CLL) are at an increasing risk of infectious morbidity and mortality . Infections are generally due to bacteria and influenced by the degree of hypogammaglobulinemia; although, in more advanced stages of disease they may also be contributed by neutropenia due to bone marrow infiltration and/or cytotoxic therapy . Furthermore, defect in cell-mediated immunity appears to be a predisposing factor to infections in patients treated with newer purine analogues . Controversies surrounding the pathogenesis of infectious complications in CLL raise several questions on their management . Patients with advanced disease who receive cytotoxic therapy might qualify for antibacterial prophylaxis . Intravenous immunoglobulin (IVIG), although of scientific interest, may be of little relevance at the present time . The new growth factors should be tested in well-designed prospective studies.

Insect Biochem Mol Biol, 1994 Apr, 24(4), 403 - 10
Purification of an insect defensin from the mosquito, Aedes aegypti; Chalk R et al.; Using a new, sensitive assay of bacterial growth inhibition, inducible antibacterial activity has been identified in the haemolymph of the mosquito, Aedes aegypti following inoculation with bacteria or with microfilariae of the filarial nematode Brugia pahangi, but not after inoculation with sterile culture medium . A lower level of antibacterial activity has also been observed in untreated individual mosquitoes . Following bacterial inoculation, a basic, inducible antibacterial peptide has been detected using native PAGE at pH 4, which corresponds with a 4.5 kDa peptide detected by tricine SDS-PAGE followed by silver staining . A peptide has been purified from immune haemolymph by ultrafiltration, followed by reversed-phase HPLC, yielding a single major peak with antibacterial activity . Partial amino acid sequence analysis of this fraction has revealed substantial homology with insect defensins . The data are consistent with the peptide being another member of this family, and we propose the name Aedes aegypti defensin.

Oral Microbiol Immunol, 1994 Apr, 9(2), 81 - 7
Oxygen-dependent modulation of release and activity of polymorphonuclear leukocyte granule products; Claesson R et al.; Polymorphonuclear leukocytes are important in the defense against the anaerobic microflora of infected gingival pockets . One part of this defense is release of antibacterial granule products by polymorphonuclear leukocytes into the pockets . The aim of the present study was to compare the efficiency of polymorphonuclear leukocytes in releasing granule products under aerobic and anaerobic conditions . Polymorphonuclear leukocytes were exposed to serum-opsonized zymosan under aerobic and anaerobic conditions . The levels of released granule products were determined by combining measurements of activity with enzyme-linked immunosorbent assays . The level of released elastase was twice as high in anaerobic as in aerobic reaction mixtures . A similar difference was not detected for myeloperoxidase . However, myeloperoxidase was inactivated after its release under aerobic conditions . The release of lactoferrin was an efficient under aerobic as under anaerobic conditions . The effect of aerobic conditions on the release of elastase and the inactivation of myeloperoxidase could be ascribed to oxidants formed in the myeloperoxidase-H2O2-chloride system . Also, the activity of the released cytoplasmic enzyme lactate dehydrogenase was inactivated by oxidants formed in the myeloperoxidase-H2O2-chloride system . These findings suggest that, in the anaerobic environment of the gingival pocket, elastase and possibly also other azurophilic granule products are released in higher amounts than under fully oxygenated conditions . In this environment, the released products may also escape inactivation by the myeloperoxidase-H2O2-chloride system.

Rev Latinoam Microbiol, 1994 Apr-Jun, 36(2), 101 - 6
{Pseudomonas microcins: characterization and effect of iron concentration}; Barberis IL et al.; Antibacterial substances were found in Pseudomonas, they were heat and trypsin resistant, molecular weight less than 10,000 daltons, produced in minimal media, optimum pH 7.0 . Methionine and glycine inhibited them; other amino acids produced less antagonistic effect . An inverted relationship between susceptibility to microcin and Fe3+ concentration was observed in experiments with iron-depleted strains . Pseudomonas was sensitive to its own microcin in iron-free medium; this is an important finding in the study of the immunity of microcin-producing strains.

J Hosp Infect, 1994 Apr, 26(4), 279 - 86
Tests for the antibacterial activity of surgical glove material; Newsom SW et al.; In-vitro and in-vivo models for testing the antibacterial activity of glove materials are described . The models were tested using four types of material: latex containing residual accelerator, latex treated by solvent-extraction to remove accelerator, material from hypo-allergenic accelerator-free gloves, and latex coated with quaternary ammonium compounds . In-vitro tests revealed two distinct types of antibacterial activity, one related to the accelerator which was slow-acting, and not neutralizable, and a second faster-acting neutralizable activity due to the quaternary ammonium compounds . The antiseptic coated material also showed antibacterial activity on human skin.

Antibiot Khimioter, 1994 Apr, 39(4), 52 - 5
{Activity of ethics committees in clinical trials of antibacterial drugs}; Melikhov OG et al.; Clinical trials are designed and conducted worldwide in accordance with International Rules of Good Clinical Practice (GCP) . The guidelines are aimed at establishing a system ensuring personal integrity and welfare of trial subjects . A significant point of the activity of Ethics Committees in GCP is protection of trial subjects . The experience of the local Ethics Committee of the Smolensk Medical Institute with protection of clinical trials of antibacterials is presented . The importance of setting up Ethics Committees for supervision of clinical trials in Russia is emphasized.

Antibiot Khimioter, 1994 Apr, 39(4), 48 - 51
{Antibacterial action of the polymeric antiseptic catapol}; Zaikina NA et al.; Activity of a polymer derivative of catamine AB, the antiseptic catapol, against gram positive and gram negative bacteria was studied . The effect of catapol on structural components of bacterial cells and permeability of bacterial cell membranes was investigated . The possibility of varying the susceptibility of bacteria to catapol and the effect of catapol on bacteria susceptible to antibiotics were evaluated . It was shown that by its in vitro antibacterial activity, catapol does not significantly differ from catamine AB.

Pathol Biol (Paris), 1994 Apr, 42(4), 297 - 304
{Placental penetration of cefpirome (HR 810): study of fetal concentrations after in vitro infusions of human placenta at term}; Closse C et al.; Cefpirome (CPO) is a new parenteral cephalosporin with a wide antibacterial spectrum . In order to explore the possibility of using CPO in late pregnancy, we studied its placental transfer in vitro in a model of human placenta infusion . Mother-to-foetus in vitro transfer of CPO is high, similar to that of amoxicillin, with a placental clearance index of 0.20 . A pharmacokinetic simulation based upon this result and data from literature suggests that CPO concentrations in foetal blood and amniotic fluid should be appropriate for the treatment of severe materno-foetal infections in late pregnancy . These preliminary results need to be confirmed by in vivo pharmacokinetic and clinical studies before recommending the use of CPO in late pregnancy.

Zentralbl Veterinarmed B, 1994 Apr, 41(2), 101 - 12
Antibacterial susceptibility of bovine-mastitis pathogens tested directly in milk from infected quarters; Louhi-Lehtio M et al.; Antibacterial susceptibilities of bovine-mastitis pathogens were analysed directly in 57 mastitic milk samples without inoculation with exogenous organisms . Aseptically collected milk was mixed with serial dilutions of antibacterials and the growth was observed using 2,3,5-triphenyltetrazolium chloride (TTC) reduction the following day . The results were compared with those obtained by using calibrated bacterial inocula in turbidimetric minimum-inhibitory-concentration (MIC) determination in broth cultures, and in TTC-broth culture-test and TTC-normal milk-test . The results of different methods all correlated positively when the entire data was used . However, taking the direct test in mastitic milk as the 'true' result, the total discrepancies varied from 34.7% to 48.8% . Antibacterial activities of the trimethoprim-sulphadoxine combination, and of spiramycin and ampicillin, decreased significantly when nutrient broth was replaced by milk as the test medium . The efficacy of trimethoprim-sulphadoxine as an antibacterial agent was also dependent on the source of milk.

Proc Natl Acad Sci U S A, 1994 Mar 29, 91(7), 2602 - 6
Cytolytic and antibacterial activity of synthetic peptides derived from amoebapore, the pore-forming peptide of Entamoeba histolytica; Leippe M et al.; The pore-forming peptide amoebapore is considered part of the cytolytic armament of pathogenic Entamoeba histolytica . Amoebapore is composed of 77 amino acid residues arranged in four alpha-helical domains . For structure-function analysis, synthetic peptides were constructed corresponding to these four domains: H1 (residues 1-22), H2 (25-39), H3 (40-64), and H4 (67-77) . The peptides H1 and H3, representing two highly amphipathic alpha-helical regions of amoebapore, possessed pore-forming activity . Peptide H3 displayed cytolytic and antibacterial functions similar to those of natural amoebapore . The most potent antibacterial activity and the broadest activity spectrum were expressed by H1-Mel, a hybrid molecule composed of the N-terminal alpha-helix of amoebapore and the C-terminal hexapeptide of melittin from the venom of Apis mellifera.

J Med Chem, 1994 Mar 18, 37(6), 733 - 8
Synthesis and antibacterial activity of new quinolones containing a 7-{3-(1-amino-1-methylethyl)-1-pyrrolidinyl} moiety . Gram-positive agents with excellent oral activity and low side-effect potential; Hagen SE et al.; A series of the R and S isomers of 7-{3-(1-amino-1-methylethyl)-1-pyrrolidinyl}-1,4-dihydro-4-oxoquinoline- and 1,8-naphthyridine-3-carboxylic acids was prepared to determine the effect on potency of the two methyl groups adjacent to the distal nitrogen in the pyrrolidinyl moiety . The antibacterial efficacy of these dimethylated derivatives was compared to the relevant 7-{3-(aminomethyl)-1-pyrrolidinyl} parent compounds and, to a lesser extent, the 7-{3-(1-aminoethyl)-1-pyrrolidinyl} analogues . The activity of the title and reference compounds was assayed in vitro using an array of Gram-negative and Gram-positive organisms and in vivo using a mouse infection model . Selected derivatives were then screened for potential side effects in a phototoxicity mouse model and an in vitro mammalian cell cytotoxicity protocol . The results showed that the R isomer displayed a 2-20-fold advantage in activity in vitro and a 2-15-fold advantage in vivo over the S isomer . Although equipotent to the 7-{3-(aminomethyl)-1-pyrrolidinyl} parent compounds in vitro, the R isomers of the 7-{3-(1-amino-1-methylethyl)-1-pyrrolidinyl} analogues showed a dramatic increase in in vivo potency, especially via the oral route of administration . These same R isomers also appeared to possess a reduced risk of phototoxicity and cytotoxicity . This combination of superior in vivo performance with a low degree of phototoxicity and mammalian cell cytotoxicity recommends these agents for further study . Of these agents, naphthyridine 16-R represents the optimal blend of potency and safety.

J Pharm Sci, 1994 Mar, 83(3), 332 - 5
Synthesis and some physiochemical properties of 2-hydroxy-N-(3,4-dimethyl-5-isoxazolyl)-1,4-naphthoquinone 4-imine derivatives; Sperandeo NR et al.; Some derivatives of 2-hydroxy-N-(3,4-dimethyl-5-isoxazolyl)- 1,4-naphthoquinone 4-imine (3), a poorly soluble drug, were synthesized in an attempt to improve their physicochemical properties . The new compounds were characterized by spectroscopic methods including an iterative NMR method (the LAOCOON III program) . The physicochemical properties such as solubility, relative lipophilicity (RM), and partition coefficients (Leo-Hansch fragmental system) were determined . Some derivatives were more lipophilic than 3 and one was water soluble . In vitro antibacterial activity was also reported for some derivatives.

Anal Biochem, 1994 Mar, 217(2), 231 - 5
Isolation and identification of cecropin antibacterial peptides from the extracellular matrix of the insect integument; Lee WJ et al.; A method for the screening and isolation of antibacterial peptides from the extracellular insect cuticle using ultrafiltration and reverse-phase high-performance liquid chromatography is presented . Using this method we were able to conveniently isolate cuticular antibacterial peptides belonging to the cecropin family in 1 day . The procedure should facilitate the rapid screening of antibacterial peptides or other bioactive peptides from extracellular matrices.

Pharmacotherapy, 1994 Mar-Apr, 14(2), 147 - 52
Comparison of ampicillin-sulbactam and ticarcillin-clavulanic acid in patients with chronic renal failure: effects of differential pharmacokinetics on serum bactericidal activity; Hardin TC et al.; STUDY OBJECTIVES . To evaluate the pharmacodynamic antibacterial activity of ticarcillin-clavulanic acid (T-C) and ampicillin-sulbactam (A-S) combinations against reference bacterial strains in patients with end-stage renal disease maintained on long-term hemodialysis . DESIGN . Randomized, crossover, controlled study . SETTING . National Institutes of Health-funded general clinical research unit in a Veterans Administration Medical Center . PATIENTS . Nine adult men with end-stage renal disease maintained on long-term hemodialysis . Two subjects did not complete the study due to problems of vascular access, and another withdrew for personal reasons . INTERVENTIONS . On a nondialysis day, each subject was randomly administered either T-C 3.1 g or A-S 3 g as a slow intravenous infusion over 30 minutes . Serial blood samples were collected for measurement of antibiotic serum concentrations and determination of serum bactericidal titers . Following a washout period, the study was repeated with the alternative antibiotic combination . MEASUREMENTS AND MAIN RESULTS . The mean observed apparent beta-half-life of clavulanic acid was substantially shorter than that for the other three drugs . The bactericidal activity of both A-S and T-C against non-beta-lactamase-producing (N beta-LP) strains of S . aureus and E . coli was consistently high, as indicated by geometric mean SBTs of at least 1:5 at 24 hours . Against beta-lactamase-producing (beta-LP) S . aureus, the geometric mean SBTs for A-S were at least 1:25 throughout the study period, while the geometric mean SBTs for T-C decreased over 24 hours from 1:29 to 1:6 . Against beta-LP E . coli, the bactericidal activities for both A-S and T-C were poor, with geometric mean peak SBTs of only 1:6 and 1:3, respectively . The geometric mean SBT for T-C against this E . coli strain had declined to 1:1 at 6 hrs . CONCLUSION . Increasing the dosing interval for T-C in patients with end-stage renal disease may lead to periods of insufficient clavulanic acid to protect ticarcillin from beta-lactamase degradation.

Klin Padiatr, 1994 Mar-Apr, 206(2), 92 - 4
{Successful treatment of therapy refractory shock lung in a newborn infant with congenital varicella using extracorporeal membrane oxygenation}; Reiterer F et al.; A newborn with congenital varicella complicated by varicella pneumonia was transferred to our hospital on day 16 of life for the consideration of extracorporeal membrane oxygenation (ECMO) . The newborn received varicella zoster immunoglobulin 13 hours after birth since the mother developed a varicella exanthema two days before delivery . On day 10 of life the newborn became clinically symptomatic with red macules and pustules . The chest roentgenogram revealed reticular pulmonary infiltrates in the right upper lobe . Antibacterial chemotherapy was initiated . In the following days the cutaneous lesions progressed, and respiratory symptoms like tachypnoea and oxygen dependence occurred . Chest roentgenograms revealed diffuse reticular and patchy pulmonary infiltrates . On day 14 of life antiviral chemotherapy with acyclovir was started . ECMO was initiated in the veno-arterial mode on day 17 due to severe respiratory failure despite maximal conventional assisted ventilation and carried out for 14 days . With the age of 10 weeks he was discharged from the hospital with mild chronic lung disease without oxygen requirements and without neurological handicap . ECMO might be considered as life saving support in newborns with severe congenital varicella, considered to have a high mortality risk.

J Antibiot (Tokyo), 1994 Mar, 47(3), 349 - 56
New oleandomycin 9-oximes . Synthesis, characterization and biological activity; Lazarevski G et al.; A series of the novel oleandomycin 9-oximes has been prepared and characterized by spectroscopic data and X-ray analysis . The antibacterial in vitro activities of the oximes (6-10) were compared with that of oleandomycin (1) . Among the novel derivatives the most active compound was 8(R)-methyloleandomycin-9-oxime (9) in contrast ot its 8(S)-isomer (10) which possessed only low potency . Some preliminary pharmacokinetic data of 9 confirmed its activity . Compound 9 has been advanced to further biological study.

Farmaco, 1994 Mar, 49(3), 197 - 200
Trifluoromethylcontaining sulfanilamides . I . Synthesis and in vitro antibacterial activity; Vigorita MG et al.; In a wider research directed to improve pharmacological profiles of known anti-infective agents by introducing fluorine or trifluoromethyl groups, some sulfanilamides trifluoromethylsubstituted on N1 ring, were synthesized and examined for their in vitro activity against gram-positive and gram-negative bacteria . Two N1-trifluoromethylphenyl-sulfanilamides, 1 and 4, exhibited MIC values, against all tested bacteria, similar or lower than those of the "classical" sulfanilamides, assayed in comparison . The new sulfanilamide 4 appears to be the more interesting: in fact, the presence of p-aminobenzoic acid (PABA) in culture medium did not influence its MIC values and no synergy was observed with trimethoprim, suggesting mechanism of action different from that of known sulfanilamides.

Ann Soc Belg Med Trop, 1994 Mar, 74(1), 51 - 9
Antiparasitic activity of diallyl trisulfide (Dasuansu) on human and animal pathogenic protozoa (Trypanosoma sp., Entamoeba histolytica and Giardia lamblia) in vitro; Lun ZR et al.; Garlic (Allium sativum L.) and one of its major components, allicin, have been known to have antibacterial and antifungal activity for a long time . Diallyl trisulfide is a chemically stable final transformation product of allicin which was synthesized in 1981 in China and used for treatment of bacterial, fungal and parasitic infections in man . The activity of diallyl trisulfide was investigated in several important protozoan parasites in vitro . The IC50 (concentration which inhibits metabolism or growth of parasites by 50%) for Trypanosoma brucei brucei, T.b . rhodesiense, T.b . gambiense, T . evansi, T . congolense and T . equiperdum was in the range of 0.8-5.5 micrograms/ml . IC50 values were 59 micrograms/ml for Entamoeba histolytica and 14 micrograms/ml for Giardia lamblia . The cytotoxicity of the compound was evaluated on two fibroblast cell lines (MASEF, Mastomys natalensis embryo fibroblast and HEFL-12, human embryo fibroblast) in vitro . The maximum tolerated concentration for both cell lines was 25 micrograms/ml . The results indicate that the compound has potential to be used for treatment of several human and animal parasitic diseases.

Boll Chim Farm, 1994 Mar, 133(3), 163 - 6
Synthesis of nucleosides of 5,7-disubstituted pyrido {2,3-d} pyrimidines and their antibacterial activity; Gupta A et al.; Synthesis of 4-amino-5,7-diphenyl-1-(beta-D-ribofuranosyl)pyrido{2,3-d} pyrimidin-2-ones nucleoside, 4-amino-5,7-disubstituted-1-(beta-D-ribofuranosyl) pyrido {2,3-d} pyrimidin-2-thiones nucleosides, 2-thioxo-3,5,7-triphenyl-1- (beta-D-ribofuranosyl) pyrido {2,3-d} pyrimidin-4 (3H) ones nucleoside and 3,5,7-triphenyl-1-(beta-D-ribofuranosyl) pyrido {2,3-d} pyrimidin-2,4 (3H) diones nucleoside have been reported . The elemental analyses, IR and 1H NMR spectral data confirm the structure of the compounds . The synthesized nucleosides have been tested for antibacterial activity and found to be more active than the pyrido {2,3-d} pyrimidines.

Vet Q, 1994 Mar, 16(1), 27 - 33
Bovine leukocyte adhesion deficiency--clinical course and laboratory findings in eight affected animals; Muller KE et al.; The clinical course of Bovine Leukocyte Adhesion Deficiency (BLAD) in eight Holstein Friesian cattle is described . Affected animals were presented with a history of poor thriving and recurrent bacterial infections . Five of these animals had to be killed because of severe respiratory disease shortly after admittance . Three affected animals survived calfhood only as a result of frequent antibacterial treatments . At one year of age, failure to thrive and stunted growth were still evident, but infections requiring antibiotic treatments occurred only sporadically . Clinical manifestations of BLAD were found in the digestive system (gingivitis, periodontitis, alveolar periostitis, diarrhoea), the respiratory system and the skin (impaired wound healing, chronic dermatitis) . A leukocytosis based on a mature neutrophilia, which persisted during infection-free periods, was observed in all animals . Granulocytes were substantially deficient of beta 2-integrin expression on their membranes . Anaemia, which was noted in four animals, may be related to the Anaemia of Inflammatory Disease Complex (AID) . The serum total protein content increased with time and was associated with elevated gamma-globulin levels . We suggest that, at a certain age, animals affected with BLAD are able to cope with environmental agents due to compensatory mechanisms of the immune system.

Trans R Soc Trop Med Hyg, 1994 Mar-Apr, 88(2), 132 - 5
Approaches to vector control: new and trusted . 1 . Humoral immune responses in blackfly and mosquito vectors of filariae; Ham PJ et al.; The vectors of filariasis, mosquitoes and blackflies, are capable of mounting a defence response to the infection . This selective review describes the molecules that are involved in these immune systems . Several antibacterial peptides are known to be induced and secreted into the haemolymph by the fat body and the circulating haemocytes . In addition, haemagglutinating lectins with carbohydrate specificities to the surface of the developing filarial larvae appear . Activation of a range of proteases occurs rapidly as does activation of the prophenoloxidase pathway . The possible roles of these and other molecules is discussed, together with mention of a working hypothesis as to how these molecules may be regulated.

Vestn Khir Im I I Grek, 1994 Mar-Apr, 152(3-4), 79 - 82
{The early diagnosis of postoperative suppuration in endoprosthesis of the hip joint}; Arutcheva AA et al.; The authors describe the method of control of the course of an early wound process in patients with endoprosthesis of the hip joint in early postoperative period, which is based on determination of the level of lysozyme in the wound . The method allows detection of the development of suppuration and start of antibacterial therapy in the early postoperative period, before the appearance of the clinical symptoms.

Insect Biochem Mol Biol, 1994 Mar, 24(3), 271 - 81
Structure and induction of a lysozyme gene from the tobacco hornworm, Manduca sexta; Mulnix AB et al.; Lysozyme is hypothesized to play a central role in initiating and maintaining the antibacterial defense response of Manduca sexta . We isolated a cDNA clone encoding a M . sexta lysozyme . Results of Northern blot analyses using this cDNA as a probe indicated that the abundance of lysozyme transcripts increased in seven tissues following treatment with peptidoglycan, with the highest level of accumulation occurring in the fat body . An analysis of the kinetics of accumulation of the transcripts in the fat body demonstrated low levels of transcripts in the naive larvae which increased rapidly after treatment and remained elevated over several days . A genomic fragment containing a lysozyme gene was also isolated and the nucleotide sequence and transcription start site of the gene was determined.

Biochem Biophys Res Commun, 1994 Feb 28, 199(1), 339 - 45
Apidaecin-type peptide antibiotics function through a non-poreforming mechanism involving stereospecificity; Casteels P et al.; Insect resistance to bacterial infections is dependent on the production of specialized defense peptides . We report here that lethal activities of apidaecin, a small peptide from honeybees, cannot possibly be the result of a conventional 'lytic' mechanism . Evidence includes the complete lack of membrane permeabilization, at concentrations that exceed lethal doses by four orders of magnitude, and undiminished sensitivity of apidaecin-resistant mutants to 'poreforming' peptides . In addition, the D-enantiomer of apidaecin is completely devoid of antibacterial activities . We propose therefore, that the antagonistic effects of apidaecin involve stereoselective recognition of a chiral cellular target, establishing this peptide as functionally unique among insect antibacterials . Identification of the apidaecin target may provide the scientific basis for rational drug design.

FEBS Lett, 1994 Feb 14, 339(1-2), 59 - 62
Inhibition of the Ca(2+)-activated K(+)-channel by sapecin B, an insect antibacterial protein; Shimoda M et al.; Sapecin is an antibacterial protein of the flesh fly and sapecin B is its homologue structurally similar to charybdotoxin of scorpion venom, which is known to be a K+ channel inhibitor . We found that, like charybdotoxin, sapecin B inhibits part of the voltage pulse-induced K+ currents of rat cerebellar Purkinje cells . We suggest that this effect is due to inhibition of the Ca(+)-activated K+ channel . Probably, sapecin B is a naturally occurring K+ channel inhibitor as well as an antibacterial protein.

J Med Chem, 1994 Feb 4, 37(3), 400 - 7
Dual-action cephalosporins incorporating a 3'-tertiary-amine-linked quinolone; Albrecht HA et al.; We have previously reported that linking quinolones to the cephalosporin 3'-position through an ester bond, a carbamate function, or a bond through a quaternary nitrogen produced cephalosporins with a dual mode of antibacterial action . We now describe a new class of dual-action cephalosporins, with greater chemical stability than those previously reported, in which the basic nitrogen of ciprofloxacin is bonded directly to the 3'-cephalosporin position, i.e., the two moieties are linked through a tertiary amine function . These compounds have demonstrated potent activity against a broad spectrum of Gram-positive and Gram-negative bacteria, including beta-lactam-resistant strains.

Antimicrob Agents Chemother, 1994 Feb, 38(2), 403 - 6
(6S)-6-fluoroshikimic acid, an antibacterial agent acting on the aromatic biosynthetic pathway; Davies GM et al.; (6S)-6-Fluoroshikimic acid inhibited the growth of Escherichia coli B on minimal medium (MIC, 0.25 micrograms ml-1), and it protected mice challenged intraperitoneally with the same organism (50% protective dose, 0.06 mg kg of body weight-1) . We propose that inhibitors of bacterial aromatic biosynthesis have the potential for use in human medicine.

Antimicrob Agents Chemother, 1994 Feb, 38(2), 374 - 7
Antibacterial synergism of polymyxin B nonapeptide and hydrophobic antibiotics in experimental gram-negative infections in mice; Ofek I et al.; Polymyxin B nonapeptide, derived by cleavage of the fatty acyl diaminobutyric acid from polymyxin B, is considerably less toxic, lacks bactericidal activity, and retains its ability to render gram-negative bacteria susceptible to several antibiotics by permeabilizing their outer membranes . The peptide rendered all 53 polymyxin-susceptible strains tested more susceptible to novobiocin, lowering the MIC of novobiocin eightfold or more . The combination of polymyxin B nonapeptide with novobiocin or with erythromycin administered intraperitoneally in multiple doses synergistically protected mice infected with gram-negative bacteria . This combination may be clinically useful because of the apparent rarity of the acquisition of resistance.

Pneumologie, 1994 Feb, 48(2), 131 - 9
{Pulmonary complications after bone marrow transplantation}; Teschler H et al.; Pulmonary complications represent a major cause of morbidity and mortality in patients undergoing allogenic and autologous bone marrow transplantation (BMT) . These include a broad spectrum of diseases affecting the lungs and airways, some with predominantly early time of onset (within weeks) and others late (beyond three months) after BMT . The major contributing factors to the occurrence of infectious and noninfectious pulmonary complications of BMT are the state of immunosuppression, secondary to the total body irradiation and chemotherapy used prior to BMT, and acute or chronic graft-versus-host disease . Early and accurate diagnosis by chest roentgenogram, bronchoscopy, and bronchoalveolar lavage combined with appropriate laboratory techniques is essential, as prompt specific treatment clearly has beneficial effects . An increasing number of pulmonary complications appears to be preventable by improving the conditioning regimes, accelerating engraftment and immune reconstitution, prophylactic antibacterial, antimycotic, and antiviral therapy as well as the modification of GVHD therapy.

Yakugaku Zasshi, 1994 Feb, 114(2), 73 - 9
{Study on new anti-rust disinfectants . III . Effect of alkyl chain length of N-alkyl-N-(2-hydroxy-3-phenoxy)propyl-N,N-dimethylammonium butyl phosphate on the antibacterial activity}; Makino M et al.; New anti-rust quaternary ammonium salts such as N-alkyl-N-(2-hydroxy-3-phenoxy)propyl-N,N-dimethylammonium butyl phosphate (5) {alkyl homologues are octyl (5a), decyl (5b), dodecyl (5c), tetradecyl (5d), hexadecyl (5e), and octadecyl (5f)} were synthesized in order to find the relationship between the alkyl length and the antibacterial activities . N-Alkyl-N-(2-hydroxy-3-phenoxy)propyl-N,N-dimethylammonium chloride (6) {alkyl homologues are dodecyl (6c), tetradecyl (6d), hexadecyl (6e)} were used as standard compounds in the quantitative analysis . 5c and 6c showed antibacterial activities and these activities were nearly equal to that of benzalkonium chloride (BAC), but, the activities shown by 5e, 5f and 6e were insufficient . 5c-e, showed excellent anti-rust effects, but 6c-e showed insufficient effects, because the former had a butyl phosphate anion and the latter had a chloride anion as a counter ion . 5a, b were insoluble in water . 5c showed a cloud point at 61.5 degrees C and 5d showed a cloud point at 72.0 degrees C at a 10% concentration in water . This phenomenon is similar to those of non-ionic surfactants . 5e was freely soluble in water.

J Clin Pharmacol, 1994 Feb, 34(2), 128 - 35
Adverse drug reactions in neonates; Knight M; Adverse drug reactions (ADR) are uncommon causes of admission of neonates to the neonatal intensive care unit . The neonate, however, is potentially at significant risk for adverse drug reactions because of underdeveloped mechanisms and systems for handling drugs (the Gray Baby Syndrome with chloramphenicol as a classic example), the fact that infants in neonatal intensive care units are often critically ill with multiple organ system dysfunction, that they may be on multiple drugs, and that they may present with an adverse drug reaction as a result of exposure while still a fetus . There is also a history of misadventures in the neonatal intensive care unit and newborn nurseries due to exposure to antibacterial agents that produced systemic effects from percutaneous absorption . In this review, an overview of the mechanisms of adverse drug reactions will be presented, followed by a general review of the experience of adverse drug reactions in neonates and some specific examples of current adverse drug reactions and a suggested approach for the prevention and evaluation of adverse drug reactions in neonates.

Scand J Dent Res, 1994 Feb, 102(1), 46 - 9
Triclosan-containing mouthwashes--does the nature of the solvent influence their clinical effect?
Waaler SM, Rolla G, Kjaerheim V.
The effect of triclosan on plaque inhibition was studied with various solvents . Eight subjects used the solutions as mouthwashes twice daily for 4 days while refraining from any other form of oral hygiene . Bacteriologic tests were also done with the same solutions . The study showed that the nature of the substance used to dissolve triclosan may be of clinical significance . Solutions of triclosan in polyethylene glycol, glycerol, or 3% sodium lauryl sulfate (SLS) alone showed marked antiplaque effect . (The first two solutions both contained 1.5% SLS) . However, triclosan dissolved in Tween 80 had only a negligible clinical effect . In vitro experiment showed that antibacterial tests did not correlate well with clinical data . It is proposed that the nature of the micelles of the detergents which are used to dissolve triclosan is of significant importance . Strongly charged micelles such as SLS show clinical effect, whereas less charged micelles of SLS/Tween 80 or uncharged micelles of Tween 80 alone appear not to have this effect.

J Antibiot (Tokyo), 1994 Feb, 47(2), 225 - 32
Modification of glycopeptide antibiotic eremomycin by the action of alkyl halides and study on antibacterial activity of the compounds obtained; Pavlov AY et al.; Alkylation of glycopeptide antibiotic eremomycin by the action of different alkyl halides leads, depending on the structure of alkyl halides used, to eremomycin derivatives of six types; alkylated at the N-terminus, quaternary compounds at the N-terminus, eremomycin esters, esters of eremocycin alkylated at the N-terminus, esters of eremomycin quaternised at the N-terminus, esters of eremomycin alkylated both at the N-terminus and at the aminogroup of disaccharide branch . Five compounds demonstrated high antibacterial activity in vitro, N-allyleremomycin and methyl ester of N,N-dimethyleremomycin being at least as good as the parent eremomycin.

Histochem J, 1994 Feb, 26(2), 142 - 51
Ultrastructural localization of tumour necrosis factor-alpha; Schmauder-Chock EA et al.; The application of an antibody against tumour necrosis factor-alpha (TNF) to thin sections of plastic-embedded mouse tissue has identified sites of TNF activity in normal and endotoxin-treated C3N/HeN mice . Prior to endotoxin treatment, TNF was observed in the secretory granules of the antibacterial Paneth cell and one type of crypt endocrine cell . Four hours after endotoxin treatment, these two types of intestinal cell were found to have degranulated . In addition, endotoxin treatment resulted in the appearance of TNF in the secretory granules of all eosinophils, neutrophils and monocytes in the bone marrow, spleen, lung and the proximal intestine . TNF was also observed in the internal elastic lamina (IEL) of arterioles . These results suggest that the process of TNF induction specifically targets the immune system and the vasculature . An invasive stimulus, such as circulating endotoxin, can provoke the immune cells to be armed with TNF . That same stimulus may cause arteriole smooth muscle cells to secrete TNF . TNF secretion in the presence of arteriole smooth muscle cells may play a role in the adjustment of arteriole tone . In the venules, TNF may be responsible for platelet and neutrophil accumulation which leads to embolism formation.

Chem Pharm Bull (Tokyo), 1994 Feb, 42(2), 392 - 4
Synthesis, lipophilicity studies and antibacterial properties of some novel quaternary ammonium salts; Siatra-Papastaikoudi T et al.; The synthesis of some novel quaternary ammonium salts, derivatives of 15-phenyl-decapentanoic acid, is described . Their lipophilicity was estimated applying the Hansch-Leo fragmental procedure and measured by means of reversed phase thin layer chromatography . All compounds were tested for their antibacterial activity against Gram positive and gram negative microorganisms . The less lipophilic compounds showed weak activity, mainly against gram positive microorganisms.

Arzneimittelforschung, 1994 Feb, 44(2), 178 - 81
Synthesis and biological studies on some organo-tin and lead halo and mixed halo-pseudohalo anionic complexes; Raj P et al.; Some new anionic complexes of organo-tin(IV) and lead (IV) isolated in combination of tetraorgano-ammonium phosphonium and stibonium cation(s) . L{R4-nMXnY} and L2{R2MX2Y2}, where R = C2H5, C4H9 or C6H5; M = Sn or Pb; X = Y = Cl = Br, I, N3, NCS; n = 1, 2 and L = R4M1 (M1 = N, P, Sb), whose structures were confirmed by correct elemental analyses, molar conductance values, van't Hoff factor and IR spectral studies, were synthesized and evaluated for anti-convulsant activity in vivo and antiviral and antibacterial activity in vitro . A few of them exhibited promising activity . In addition, the toxicity (ALD50) and effects on the central nervous system of these complexes have been studied in mice.

J Inorg Biochem, 1994 Feb 1, 53(2), 117 - 26
Synthesis and spectroscopy studies of copper(II) nitrate of sulfacetamide drug . Crystal structure of {Cu(sulfacetamide)2(NO3)2} . Antibacterial studies; Blasco F et al.; The structural spectroscopic, and thermal properties of a complex of sulfacetamide (Hsacm) with Cu(II) have been investigated . The complex {Cu(Hsacm)2(NO3)2} crystallizes in the monoclinic system, space group P2(1)/n . The cell dimensions are a = 7.696(7) A, b = 8.017(7) A, c = 19.230(10), beta = 110.80(1) degree, V = 1109(1) A3, Z = 2, and Dx = 1.84 g/cm3 . The structure was refined to R = 0.0776 . Cu(Hsacm)2(NO3)2 molecules form a long polymeric chain extended along the b-axis . The copper(II) coordinated geometry is tetragonally distorted octahedral with two amino nitrogens from Hsacm and two oxygens from nitrato anions in the basal plane and two acetamido oxygens from neighbor Hsacm molecules in the apical position . Each sulfacetamide, acting as a bidentate ligand, links two Cu(II) ions as a bridge through the Namino and the Oacetamido atoms . The complex proved to possess higher bacteriostatic activity than the corresponding ligand.

Nippon Rinsho, 1994 Feb, 52(2), 384 - 8
{Legionnaires' disease}; Toyoda K et al.; Among community-acquired pneumonias or hospital-acquired pneumonias, the genus Legionella, an intracellular bacteria, is one of the most important pathogens causing death . The bacteria from clinical specimens could not be cultured by ordinary methods and the polymerase chain reaction, a new method for rapid detection, has been developed; however, Legionella pneumonias are still difficult to diagnose . Antibiotics, such as macrolides, new quinolones and rifampicin, are very active against Legionella spp . These antibacterial agents should be administered when acute pneumonia tends to exacerbate with previous beta-lactams or aminoglycosides therapy . Legionella pneumonias are more likely to occur in elderly males or in the compromised-hosts with underlying diseases, such as malignancy, diabetes mellitus, AIDS, etc.

Nippon Rinsho, 1994 Feb, 52(2), 372 - 7
{Gram-negative rods: antibacterial agents effective on gram-negative rods}; Iyobe S; Some kinds of gram-negative rods cause serious infections in the compromised hosts . The species most frequently isolated in big hospitals are P . aeruginosa, E . coli, K . pneumoniae, E . cloacae, S . marcescens, and H . influenzae . Among these species . P . aeruginosa, E . cloacae and S . marcescens show resistance to many antibacterial agents . The aminoglycoside, such as gentamicin, is effective against these strains but resistant strains are detected at a high frequency for P . aeruginosa . Resistant strains to new quinolones are isolated for both S . marcescens and P . aeruginosa . The third generation cephems are effective against these species but they easily acquire resistance to these drugs . Imipenem and cefclidin are effective and a few resistant strains to the drugs are already detectable in gram-negative rods.

Nippon Rinsho, 1994 Feb, 52(2), 309 - 14
{Problems in the host defense system against bacterial infection}; Mitsuyama M; Various types of defects in the host defense system are involved in bacterial infection especially in so-called compromised host . Among the humoral factors of defense system, complement system and immunoglobulins are indispensable . Phagocytes are the most important cellular factor in the effective phagocytosis and intracellular killing of ingested bacteria through the formation of ROI, RNI and by the release of antibacterial peptides including defensin or serprocidin family . T lymphocytes are specially required when the infection is caused by intracellular parasitic bacteria for activation of macrophages through the production of several cytokines or expression of cytotoxic effect . gamma delta T cell may be involved in the first line defense . The functional significance of each factor of host defense was discussed with special reference to the escape mechanisms of bacteria.

J Nutr Sci Vitaminol (Tokyo), 1994 Feb, 40(1), 63 - 71
Effects of Houttuyniae cordata and refinery final molasses on the development of offensive odor in porcine small intestine during storage; Urabe K et al.; Porcine small intestine evolved a specific offensive odor only 0.5 to 1 day after storage at 20 degrees C . We investigated the effects of Houttuyniae cordata (dokudami), refinery final molasses (RFM), green tea, and brown sugar on the evolution of methylmercaptan and ethanol, which were the main components of the volatiles which evolved from porcine small intestine in storage . Furthermore, we determined their antibacterial effect and deodorant activity against methylmercaptan, as possible factors in reducing the offensive odor . Addition of those materials reduced the offensive odor during storage . In particular, dokudami, green tea, and RFM markedly suppressed the evolution of methylmercaptan . RFM was most effective in suppressing the growth of bacteria . Dokudami had the highest deodorant activity, comparable to that of perilla leaves . However, the retardation of methylmercaptan evolution in situ cannot be simply explained by either of deodorant or antibacterial effect . It seems likely that the combined action of both effects affects the evolution of methylmercaptan in situ.

Int Dent J, 1994 Feb, 44(1 Suppl 1), 83 - 98
Recent advances in stannous fluoride technology: antibacterial efficacy and mechanism of action towards hypersensitivity; Miller S et al.; Stannous fluoride (SnF2) is highly susceptible to oxidation and hydrolysis but both anhydrous and aqueous preparations can be well established by proper formulation . When stability in aqueous preparations is achieved by the use of certain strong complexing agents, reduced antibacterial activity is observed which may be attributed to reduced bioavailability of the stannous ion . In contrast, an anhydrous SnF2 preparation maintains stannous ion in a stable but, uncomplexed form . This preparation displays antibacterial activity in saliva and delivers stannous ion which is absorbed onto surfaces making them less susceptible to plaque formation for an extended period of time (hours) . When this anhydrous preparation is brushed onto dentine in vitro or in situ, one observes a nearly complete coverage of the dentine surface and occlusion of tubules by a tin-rich surface deposit . This finding indicates that the observed clinical efficacy of this preparation at relieving hypersensitivity is due to occlusion of tubules by a mixture of low solubility complexes of tin . A water-based SnF2 preparation containing strongly complexed stannous ions does not form a surface coating on dentine in vitro suggesting that this preparation may not be optimal for treating hypersensitivity . Overall, the findings indicate that the stannous ions in a SnF2 preparation must be maintained in a stable, bioavailable form for optimal efficacy against plaque and hypersensitivity to be obtained . The results suggest that these properties are provided by stable anhydrous preparations but are difficult to achieve simultaneously in aqueous preparations . When properly formulated, stannous fluoride preparations can provide multiple oral therapeutic benefits.

Int Dent J, 1994 Feb, 44(1 Suppl 1), 63 - 70
Recent advances in plaque, gingivitis, tartar and caries prevention technology; Gaffar A et al.; A dentifrice containing triclosan/PVM/MA, copolymer/NaF (Total) combination was compared with dentifrices containing triclosan without the copolymer system . A variety of laboratory, animal and human studies indicated that Total provided higher uptake and retention of triclosan on teeth, and was more effective in reducing plaque in chemostat and flow cell models . The retention of triclosan in dental plaque was significantly higher with Total as compared with other dentifrices 2 hours post brushing . The triclosan retained in the plaque after using Total was effective against plaque bacteria for up to 12 hours . Other dentifrices did not provide a sustained antibacterial effect against plaque . The results indicated that the delivery system with the copolymer significantly enhanced the efficacy of triclosan against plaque, gingivitis and plaque related diseases in vivo.

Eur J Clin Microbiol Infect Dis, 1994 Feb, 13(2), 161 - 5
Bacteremia due to fluoroquinolone-resistant Escherichia coli in two immunocompromised patients; Kern WV et al.; Two patients with acute leukemia developed Escherichia coli bacteremia while receiving oral ofloxacin for antibacterial prophylaxis during profound neutropenia . The isolates were resistant to ofloxacin (MIC 25 and 12.5 micrograms/ml respectively), other fluoroquinolones and several unrelated agents . Whole cell drug accumulation studies with four different fluoroquinolones suggested major differences between drugs but only minor alterations in individual drug permeability in the two resistant isolates compared with a susceptible control strain . In a supercoiling assay using the purified DNA gyrase and plasmid pBR322, high concentrations (> or = 250 micrograms/ml) of both ofloxacin and ciprofloxacin were needed for visible inhibition of enzyme activity suggesting mutations in the DNA gyrase gene as the significant mechanism of resistance in both strains.

Antibiot Khimioter, 1994 Feb-Mar, 39(2-3), 41 - 4
{Imipenem-cilastatin in the treatment of suppurative inflammatory complications in the cancer clinic}; Dronova OM et al.; The results of the treatment with imipenem/cylastatin (Merck, Sharp and Dohme) of 46 oncological patients whose condition was severe or extremely severe because of infectious complications are presented . The drug was administered intravenously drop-like in doses of 1.5 or 2 g a day . The paper also presents the data on the in vitro susceptibility of 492 strains of aerobic organisms causing purulent inflammatory and septic complications . The majority of the strains were susceptible to imipenem/cylastatin (80-100 per cent depending on the genus and species) . A complete or partial therapeutic effect was observed in 30 out of 46 patients . The adverse reactions in several cases required the use of some other drug . Still, they were not life-threatening . Therefore, imipenem/cylastatin should be considered to be a highly efficient combination with antibacterial action . It is useful in the treatment of severe purulent inflammatory complications in oncological patients.

Antibiot Khimioter, 1994 Feb-Mar, 39(2-3), 26 - 30
{The efficacy of antibacterial preparations against Pseudomonas mallei in in-vitro and in-vivo experiments}; Manzeniuk IN et al.; In vitro antibacterial activity of 43 antibiotics and chemotherapeutics against P . mallei Ts-5 was studied . The causative agent of malleus was highly susceptible to sulfanilamides, fluoroquinolones, tetracyclines, aminoglycosides, ceftazidime and imipenem . 15 antibiotics and chemotherapeutics were tested for their therapeutic efficacy on golden hamsters with experimental malleus . Combinations with trimetoprim (sulfaton and biseptol), 3rd generation quinolones (ciprofloxacin, enoxacin and ofloxacin) as well as minocycline, novobiocin and oxolinic acid were shown to be therapeutically highly efficient.

J Biol Chem, 1994 Jan 21, 269(3), 1865 - 72
Functional domains of recombinant bactericidal/permeability increasing protein (rBPI23); Little RG et al.; The 23-kDa recombinant amino-terminal bactericidal/permeability increasing protein fragment (rBPI23) has all of the antibacterial and antiendotoxin properties of the holoprotein . In the current studies, we have identified multiple active domains within rBPI23 with chemical and proteolytic cleavage fragments and with synthetic overlapping peptides . We also demonstrate a novel, high affinity heparin binding property for rBPI23, in addition to its established bactericidal and lipopolysaccharide binding properties . Cleavage fragments and synthetic, overlapping peptides of rBPI23 were analyzed for inhibition of the lipopolysaccharide-induced Limulus amebocyte lysate reaction, for bactericidal activity, and for heparin binding . Three separate, active domains were identified in amino acid regions 17-45, 65-99, and 142-169 . A single synthetic peptide (85-99) was bactericidal . These results indicate that rBPI23 is comprised of three separate functional domains which contribute to the high affinity interaction of rBPI23 with Gram-negative bacteria . The individual activity of each domain and the cooperative interaction among domains provide the basis for developing rBPI23 analogues with increased biologic efficacy.

FEBS Lett, 1994 Jan 17, 337(3), 303 - 7
Chemical synthesis and biological activity of a novel antibacterial peptide deduced from a pig myeloid cDNA; Storici P et al.; Several myeloid precursors of antibacterial peptides have recently been shown to share homologous pre- and pro-regions . Taking advantage of this homology, a novel cDNA was cloned from pig bone marrow RNA . This encodes a 166-residue polypeptide with highly conserved pre- (29 residues) and pro- (101 residues) sequences, followed by a unique, 36-residue C-terminal sequence . Structure analyses of this C-terminal region have identified a highly cationic sequence predicted to adopt an amphipathic alpha-helical conformation . A peptide corresponding to this sequence was chemically synthesized and shown to arrest the growth of both Gram-positive and Gram-negative bacteria . At least for Escherichia coli, the activity of this peptide appears to be mediated by its ability to permeabilize the bacterial membranes.

Cas Lek Cesk, 1994 Jan 3, 133(1), 22 - 4
{Peroral preparations of cephalosporin antibiotics}; Babalova M et al.; Three successful generations of cephalosporin antibiotics can be divided into parenteral and peroral substances . Both have similar antibacterial and hence therapeutical properties . It is usual to include into the first generation of peroral cephalosporins the so-called phenylglycine, or hydroxyphenylglycine derivatives . The carbacephem variant of Cefaclor (Panoral Lilly), Loracarbef, however, has improved properties and although it is a phenylglycine drug, it could be classified as a second generation cephalosporin . Here we include also the so-called ester-prodrugs: 2nd generation parenteral cephalosporins esterified in the position of C4 (cefuroxime-axetil, Zinnat, cefpodoxime-proxetil, Oralox, etc.) . They are broad-spectrum antibiotics, not hydrolysed by resistant bacteria, and, hence, they are effective also against cephalosporin-(1 . generation) resistant strains . New structures of cephalosporins, e.g . cefixime and ceftibuten (Cedax) could be classified as cephs of the 3rd generation . They, are stable even against destruction by strains resistant to Cefotaxime or Ceftazidime, and, thus, effective against such bacteria, whose number is expected to increase in the near future . It is concluded that the possibility to administer cephalosporins having different properties, spectrum and stability by both parenteral and peroral way is highly welcomed mainly in pediatric practice and that there are several new and promising drugs in this still developing group of antibacterials.

Folia Microbiol (Praha), 1994, 39(6), 471 - 4
Structure-activity relationships of some 4-quinazolylthiosemicarbazides and their triazolo derivatives; Jantova S et al.; Eight 4-quinazolylthiosemicarbazides and nine of their structural analogues have been tested for antibacterial effects and for structure activity relationships . 9-Chloro-5-morpholino-1,2,4-triazolo{4,3-c}quinazoline-3-thione has demonstrated the highest antibacterial effect (MIC of 1 mg/L for E . coli and P . mirabilis and < 1 mg/L for S . aureus and B . subtilis) . The most effective derivatives have the carbon aromatic ring substituted with chlorine and the pyrimidine ring with morpholine or with secondary amine group.

Clin Exp Dermatol, 1994 Jan, 19(1), 26 - 30
Verrucous carcinoma of the face with a massive neutrophil infiltrate . Analysis of leucocyte chemotactic activity in the tumour extract; Takematsu H et al.; An unusual case of verrucous carcinoma of the face with a massive infiltration of neutrophils was found in a 60-year-old Japanese man who presented with a scaly, crusty tumour studded with pustules of 3 years duration on the left cheek . Histological examination showed a proliferation of deceptively benign-looking epidermal cells with an intact basement membrane, accompanied by a dermal infiltration of neutrophils and mononuclear cells and formation of microabscesses containing multinucleate giant cells, suggesting deep fungal infection or blastomycosis-like pyoderma . The lesion, however, was unresponsive to antifungal or antibacterial treatments and ultimately attained a considerable size in the following months . Based on the findings of repeat biopsy conducted 4 months later indicating further deeper invasion, a diagnosis of verrucous carcinoma of the face was made, and a total excision of the tumour and left cervical lymph node dissection were finally carried out . It can be speculated that aberrant production of leucocyte chemotactic cytokines such as interleukin-8 by dysplastic keratinocytes, subsequent neutrophil infiltration/serum permeation, generation of leucotactic anaphylatoxin C5a from serum through complement activation and of lipid chemotactic factors (leukotriene B4 and 12-hydroxy-eicosatetraenoic acid) by infiltrating leucocytes and/or dysplastic keratinocytes provoked the characteristic accumulation of neutrophils in the verrucous carcinoma of this case.

J R Soc Med, 1994 Jan, 87(1), 9 - 12
Susceptibility of Helicobacter pylori to the antibacterial activity of manuka honey; al Somal N et al.; Honey is a traditional remedy for dyspepsia, and is still used for this by some medical practitioners although there is no rational basis for its use . The finding that Helicobacter pylori is probably the causative agent in many cases of dyspepsia has raised the possibility that the therapeutic action of honey may be due to its antibacterial properties . Consequently, the sensitivity of Helicobacter pylori to honey was tested, using isolates from biopsies of gastric ulcers . It was found that all five isolates tested were sensitive to a 20% (v/v) solution of manuka honey in an agar well diffusion assay, but none showed sensitivity to a 40% solution of a honey in which the antibacterial activity was due primarily to its content of hydrogen peroxide . Assessment of the minimum inhibitory concentration by inclusion of manuka honey in the agar showed that all seven isolates tested had visible growth over the incubation period of 72 h prevented completely by the presence of 5% (v/v) honey.

Ter Arkh, 1994, 66(3), 46 - 50
{The clinico-immunological evaluation of the ribomunyl treatment of chronic bronchitis patients}; Borisova AM et al.; The paper reports the results of ribomunil trial in chronic bronchitis (CB) patients who suffered from frequent exacerbations . The drug was found to act primarily on a phagocytic component of the immunity and local immunity of the respiratory mucosa . Because of its vaccine-like effect, ribomunil administration is most beneficial in CB remission . Ribomunil treatment results in reduction of the number and duration of CB exacerbations, of the scope of antibacterial therapy.

Annu Rev Med, 1994, 45, 421 - 34
Modulation of the ionic milieu of the airway in health and disease; Noone PG et al.; Airway surface liquid (ASL) is an integral part of lung defense mechanisms . Ion transport by airway epithelia regulates the volume and composition of this fluid . A better understanding of the mechanisms of ion transport will enable the development of new therapies for airway diseases associated with defects in these mechanisms . A useful model of a disease with abnormal airway epithelial ion transport is cystic fibrosis (CF), a distinct genetic syndrome of altered lung defense mechanisms characterized by chronic bacterial infection and a steady decline in lung function . Traditional therapies for CF include antibacterial drugs and augmentation of clearance of secretions, but investigators are now studying pharmacological approaches to target the more basic defect of the disease, i.e . abnormal sodium and chloride ion transport . Early treatment in childhood, prior to lung damage, might prevent or at least retard the decline in pulmonary function that remains the hallmark of CF . Ion transport dysfunction may also contribute to other airway diseases such as asthma and chronic bronchitis . Pharmacological intervention at this level may prove beneficial in these common lung diseases as well.

Nephrol Dial Transplant, 1994, 9(2), 156 - 62
Antibacterial peritoneal defence in automated peritoneal dialysis: advantages of tidal over continuous cyclic peritoneal dialysis?
de Fijter CW, Verbrugh HA, Oe PL, Heezius EC, Verhoef J, Donker AJ.
In tidal peritoneal dialysis (TPD) only a part of the infused dialysate is drained with each exchange, leaving a residual volume on top of which fresh fluid is cycled . As the persistent presence of a buffered intraperitoneal reserve volume might favour peritoneal macrophage (PMO) function, PMO obtained from eight patients during a 3-h continuous cyclic peritoneal dialysis (CCPD) or TPD session were studied in a randomized cross-over trial . PMO were studied for uptake of E . coli (complement-dependent) and S . epidermidis (antibody-dependent), as well as for their killing capacity and peak chemiluminescence response . In addition, dialysate was sampled during both treatment sessions and studied for pH, osmolality, and effect on the viability of donor phagocytes and mesothelial cells . TPD-derived PMO were significantly better able to phagocytose E . coli than CCPD-PMO (48 +/- 8 versus 33 +/- 6% uptake, P < 0.05), whereas the other tested functional capacities revealed no significant difference between TPD- and CCPD-PMO . During TPD dialysate pH ranged from 6 to 7 as compared to a pH range from 5 to 7 in CCPD . The presence of a residual dialysate volume resulted in less wash-out of cells and opsonins early in the treatment, and to some extent blunted the noxious effects of fresh dialysis solutions . Overall, however, tidal PD appeared to have no advantage over CCPD regarding preservation of peritoneal defences.

J Biochem (Tokyo), 1994 Jan, 115(1), 82 - 6
Purification and molecular cloning of cDNA for an inducible antibacterial protein of larvae of a coleopteran insect, Holotrichia diomphalia; Lee SY et al.; Injection of Escherichia coli into larvae of the coleopteran Holotrichia diomphalia results in the appearance of antibacterial activity in the hemolymph . An antibacterial protein, named holotricin 2, was purified from larvae of this insect and characterized . A cDNA clone for holotricin 2 was isolated and its complete sequence was determined . This protein was found to inhibit the growth of Gram-negative bacteria and to consist of 72-amino acid residues with no cysteine residues . Its amino acid sequence is similar to that of coleoptericine, an antibacterial protein isolated from larvae of the coleopteran Zophobas atratus.

Br J Clin Pract, 1994 Jan-Feb, 48(1), 5 - 7
Penicillin allergy: a study of incidence as reported by patients; Kerr JR; To assess the incidence of penicillin allergy as reported by patients to doctors, a 5-month study was undertaken in a university teaching hospital . The study design was prospective, and included all hospital patients for whom advice on clinical management was given by one bacteriology registrar and in whom the previous response to penicillin was considered . Of the 271 patients included in the study, 21 reported penicillin allergy . The most commonly reported symptom was localised rash (8 cases), followed by unknown reaction symptoms (6), nausea with or without vomiting (3), generalised itchy rash with difficulty in breathing (3), and localised rash with chest pain (1) . Three of 21 cases reported generalised rash with difficulty in breathing; two of these followed intravenous penicillin administration . If the three cases of generalised itchy rash with difficulty in breathing are taken as true type-1 hypersensitivity to penicillin, the incidence of this was 1.11% (3 of 271), and the incidence of true allergy among patient-reported allergy was 14.3% (3 of 21) . In two cases of reported penicillin allergy a penicillin was administered for treatment of the current infection, despite the history and without any ill-effects . Penicillins are non-toxic and inexpensive and, despite the number of alternatives for antibacterial therapy, are still the treatment of choice for many infections . More attention should therefore be paid to details of the clinical history relating to penicillin allergy with a view to decreasing the number of patients labelled 'penicillin-allergic'.

Probl Tuberk, 1994, (1), 35 - 8
{State of the hemostasis system in patients with pulmonary tuberculosis undergoing endobronchial laser therapy}; Kamaletdinov IM et al.; Blood coagulation has been studied in 59 patients with pulmonary tuberculosis running in association with nonspecific endocarditis following a course of endobronchial laser (He-Ne or CO2 units) radiation . The treatment resulted in intensification of intravascular hemocoagulation . On after-treatment month 5-8 hemostatic disorders in the above patients were less manifest than in matched patients treated with antibacterial drugs combined with standard endobronchial therapy.

Probl Tuberk, 1994, (1), 28 - 30
{Sjogren's syndrome and the "dry syndrome" in combination with lung diseases}; Ozerova LV et al.; Four cases of Sjogren's disease are reported: 2 cases with pulmonary syndrome (fibrosing alveolitis) and 2 cases with respiratory sarcoidosis . The diagnosis was made basing on xerostomia and xerophthalmia . Corticosteroid treatment produced only a partial response . The disease took a chronic course in all the patients . Antibacterial drugs were a failure in all the patients.

J Ethnopharmacol, 1994 Jan, 41(1-2), 71 - 6
Bioactivity of certain Egyptian Ficus species; Mousa O et al.; The fruit extracts of Ficus sycomorus L., F . benjamina L., F . bengalensis L . and F . religiosa L . were screened for bioactivity . F . bengalensis and F . religiosa demonstrated activity in the brine shrimp test (Artemia salina) which indicates toxicity, whereas F . sycomorus and F . benjamina showed no activity . All the fruit extracts exhibited antitumor activity in the potato disc bioassay . None of the tested extracts showed any marked inhibition on the uptake of calcium into rat pituitary cells GH4C1 . The extracts of the four tested Ficus species had significant antibacterial activity, but no antifungal activity . The results of this preliminary investigation support the traditional use of these plants in folk medicine for respiratory disorders and certain skin diseases.

Ter Arkh, 1994, 66(2), 45 - 7
{The pharmacodynamic and ulcer-healing action of modern anti-ulcer agents}; Gorshkov VA et al.; In a study of 159 duodenal ulcer patients the authors studied the effect of H2-blockers, antibacterial and sucralfate monotherapy on the frequency of the ulcer healing, Helicobacter pylori (HP) infection and acid-proteolytic aggression in the body and antropyloric portion of the stomach . All the drugs were found to exhibit similar antiulcer activity . Inhibition of the acid-proteolytic aggression in the gastric body was registered only under the action of H2-blockers . Antibacterial preparations inhibited the growth of HP, but did not affect the acidity and proteolysis in the gastric body . Neither did sucralfate which also had no effect on microorganisms . All the test drugs were able to reduce antropyloric acidity, thus promoting healing of the ulcer.

Mol Gen Genet, 1994 Jan, 242(2), 152 - 62
The lysozyme locus in Drosophila melanogaster: an expanded gene family adapted for expression in the digestive tract; Daffre S et al.; Lysozyme has been studied in insects as part of the system of inducible antibacterial defence in the haemolymph . We recently found two Drosophila lysozyme genes that are constitutively expressed in the digestive tract, and are probably involved in the digestion of bacteria in the food . To obtain an overview of the lysozyme genes in this species and their possible roles in immunity and digestion, we have now characterized all six lysozyme genes in the cloned part of the lysozyme locus at 61F, and a seventh gene that maps to the same chromosomal location . The expression of the genes follows four different patterns: firstly, four closely related genes, LysB, C, D and E, are all strongly expressed in the midgut of larvae and adults; secondly, LysP is expressed in the adult salivary gland; thirdly, LysS is expressed mainly in the gastric caecae of larvae; and finally, LysX is primarily expressed in the metamorphosing midgut of late larvae and early pupae . The LysD-like genes and LysS are strongly repressed in artificially infected animals, possibly reflecting a malaise reaction in the digestive tract . None of the genes is expressed in the fat body or haemocytes . Thus rather than being a component of the haemolymph, the Drosophila lysozymes are found mainly in the digestive tract where they are expressed at a high level . Furthermore all genes, except LysP, encode acidic proteins, in contrast to the strongly basic "typical" lysozymes . This is highly reminiscent of the situation in ruminants, where the lysozymes have been recruited for the digestion of symbiotic bacteria in the stomach.

J Nat Prod, 1994 Jan, 57(1), 18 - 26
Cytotoxic and antibacterial dihydrochalcones from Piper aduncum; Orjala J et al.; Bioactivity-guided fractionation of a CH2Cl2 extract from the leaves of Piper aduncum afforded three new dihydrochalcones, piperaduncins A {3}, B {4}, and C {5}, as well as two known dihydrochalcones, 2',6'-dihydroxy-4'-methoxydihydrochalcone {1} and 2',6',4-trihydroxy-4'-methoxydihydrochalcone {2} (asebogenin), together with sakuranetin, anodendroic acid methyl ester, and the carotenoid lutein . The structures of the isolates were elucidated by spectroscopic methods, mainly 1D- and 2D nmr spectroscopy . The proposed stereochemistry for compound 4 was deduced by NOESY spectroscopy and the corresponding energy minimum was established by molecular modelling calculations and translated into a 3D structure.

Biol Pharm Bull, 1994 Jan, 17(1), 152 - 5
Comparative study of permeability into rat cerebrospinal fluid of the quinolones: dependency on their lipophilicities; Ichikawa N et al.; Pharmacokinetic behavior involved in the entry of four quinolone antibacterial agents, norfloxacin (NFLX), ciprofloxacin (CPFX), ofloxacin (OFLX) and nalidixic acid (NA), into cerebrospinal fluid (CSF) was comparatively investigated in rats . Periodically, after the bolus i.v . dose of each quinolone (10 mg/kg), aliquots of CSF were collected by cisternal puncture and blood samples were then withdrawn from the jugular vein . CSF and serum (total and unbound) levels of the drugs were determined by HPLC method . Transport parameters for three new quinolones (NFLX, CPFX, OFLX) into CSF were obtained by physiological model analysis . Serum levels of OFLX and NFLX declined bi-exponentially with time, whereas the serum levels of NA and CPFX declined in mono-exponential and tri-exponential fashion, respectively . Fractions of each quinolone unbound to serum protein (approximately 0.7 for NFLX, CPFX, and OFLX, 0.12 for NA) were almost the same at any point in time . The CSF levels of these quinolones rose quite rapidly after drug administration, and then declined, along with their serum levels . Both the CSF level and the ratio of CSF concentration to serum unbound concentration were the highest for NA, followed by OFLX, CPFX and NFLX . These values of the four quinolones were almost proportional to the apparent partition coefficient (Papp) between n-octanol and phosphate buffer (pH 7.0) values of each reported in a previous paper {Tsuji et al., Antimicrob . Agents Chemother., 32, 190 (1988)} . In the three new quinolones, OFLX had a larger value of apparent diffusional clearance between blood and CSF (PAc) than CPFX and NFLX.(ABSTRACT TRUNCATED AT 250 WORDS)

Z Naturforsch {C}, 1994 Jan-Feb, 49(1-2), 154 - 5
Xanthanolides of Xanthium italicum Moretti and their biological activity; Tsankova ET et al.; Seven xanthanolides were identified in the extract of X . italicum leaves . Antibacterial and cytotoxic activities were found for the total extract and its major constituents xanthinin and xanthatin.

Cah Anesthesiol, 1994, 42(2), 153 - 7
{Value of HME antibacterial filters in neonatal and pediatric anesthesia . Comparison with traditional heating humidifiers}; Runti G et al.; HME (heat-moisture exchangers) filters (Hygrobaby DAR) have been compared with classical humidifiers (Bennett Cascade Humidifier) with regard to heating and humidification of inspired gases in anaesthetized neonates and infants . 28 young patients (2 days-12 months) have been randomized into two groups . Though traditional heaters-humidifiers offer slightly higher performances in terms of temperature and moisture, HME-filters appear to be a better choice from cost, handiness and safety considerations . Antibacterial efficacy of HME-filters is also a major quality.

J Biomater Sci Polym Ed, 1994, 5(6), 607 - 19
New biomaterials through surface segregation phenomenon: new quaternary ammonium compounds as antibacterial agents; Nohr RS et al.; Five new trisiloxane quaternary ammonium compounds were synthesized from hydrotrisiloxane with allyl glycidyl ether to yield the epoxy function . Various amines were then reacted to yield trisiloxane amines which were further reacted to methyl substitute or oxidize the beta-carbons in order to provide thermal stability . These new compounds were employed as melt additives in a nonwoven polypropylene fiber extrusion process to produce, through surface segregation, a new biomaterial with antibacterial properties.

Klin Khir, 1994, (1-2), 27 - 9
{Regional immunocorrective therapy using laferon in patients with suppurative cholangitis}; Nichitailo ME; In patients with purulent cholangitis after correction of major bile outflow, intracholedochal administration of laferon was used together with general and antibacterial therapy . This contributed to improvement in the function of a cellular link of immunity, decrease in intensity of autoimmune response of the own lymphocytes, stabilization of general inflammatory response of the organism which resulted in normalization of pathologically increased laboratory and biochemical indices in the blood analyses of the patients.

Infection, 1994, 22 Suppl 1, S23 - 6
Clinical evaluation of drug efficacy in UTI in men: the significance of bacterial elimination on day one; Arakawa S et al.; With the purpose of assessing whether the effect of a drug at an early stage of administration could serve to predict efficacy at the end of drug treatment, a cephem antibiotic was administered for 5 days (days 0-4) by injection in males with complicated UTI . Results showed that the bacteriological effect on day 1 was reflected in the overall clinical efficacy on day 5 . The activity of an antibacterial agent appeared to be reflected in the ability to eliminate bacteria 1 to 2 days after the start of drug administration.

Zhongguo Zhong Xi Yi Jie He Za Zhi, 1994 Jan, 14(1), 37 - 8, 6
{A study of paeonol injection on immune functions in rats}; Li FC et al.; Paeonol is the main effective component of the traditional Chinese medicine, Paeonia suffroticosa . Paeonol has some therapeutic effects in resisting many species of bacteria and fungi . But the mechanism of such effects is still unclear . We used low dosage of paeonol injection (10-15 mg/kg) to observe its effect on the functions of the immune system of the Wistar's rats . The methods include peripheral blood ANAE+ lymphocytes (PBAL), leucocyte migrating inhibition factors (LMIF), specific rosette forming cells (SRFC) of spleen, and bacteria phagocytosis of polymorphonuclear neutrophil (BPP) . The results showed that paeonol could enhance specific cellular immunity by raising the percentage of the PBAL (P < 0.01) and the release of LMIF (P < 0.01) . Paeonol could also increase the BPP (P < 0.01) . On the other hand, although it could increase the percentage of SRFC of the spleen, such an effect showed no significant difference (P > 0.1) . These enhancing effects of the specific cellular immunity and the nonspecific phagocytosis functions of the immune system might be one of the mechanisms of the antibacterial effects of paeonol . The possible modulating activity of paeonol may develop a new applied field in clinical practice.

Akush Ginekol (Mosk), 1994, (2), 32 - 5
{The clinical picture and diagnosis of bacterial vaginosis}; Kira EF; Bacterial vaginosis, a disease new in classification of vaginal infection, is described . Characteristic signs of this condition are prolonged abundant secretions from the vagina with an unpleasant odor resistant to routine antibacterial and antiinflammatory therapy . The informative criteria of the diagnosis of bacterial vaginosis are a shift of vaginal contents pH to the alkaline values, positive amino test, absence of lactic flora, and detection of clue cells in gram-stained smears . Criteria of differential diagnosis between bacterial vaginosis and nonspecific vaginitis are presented.

Klin Lab Diagn, 1994, (4), 15 - 7
{Serum antigens in the evaluation of the effectiveness of pyelonephritis therapy}; Miroshnikov VM et al.; Blood serum levels of stage-specific antigens were measured by radioimmunoassay and immunodiffusion methods in patients with acute pyelonephritis at various stages of traditional antibacterial therapy and ultraviolet autoblood irradiation . Under study were ferritin, beta 2-microglobulin, C-reactive protein, transferrin, alpha 2-macroglobulin, and haptoglobin levels . Kinetics of the measured proteins was demonstrated and the possibility of applying their identification to assessment of treatment efficacy shown . The levels of these proteins are shown to be not only indicators of inflammation and destruction in pyelonephritis, but to reflect as well the repair reactions in the body which course most actively when UV irradiation of autoblood is added to multiple-modality treatment schemes.

Acta Vet Scand, 1994, 35(2), 207 - 12
Evaluation of a cow-side test for detection of gram-negative bacteria in milk from cows with mastitis; Waage S et al.; A modified Limulus amebocyte lysate (LAL) cow-side test was evaluated under field conditions . The principle of the test is to visualize reactions between test components and endotoxin from the cell wall of Gram-negative bacteria . The practical purpose is to detect such bacteria in mastitic milk . Secretions from 789 udder quarters with clinical mastitis were examined by the LAL-test . Parallel quarter milk samples were sent to a mastitis laboratory of microbiological examination . Eleven veterinary surgeons in three veterinary districts in Norway performed the field investigations . Results of the LAL-test and culture agreed in 93% of all milk samples tested, agreement measured by kappa being 0.63 . The sensitivity of the test in detecting Gram-negative bacteria was 63%, while the specificity was 97% . The predictive value of a positive test result was 70%, the figure being somewhat higher (75%) when the material was limited to milk samples without antibiotic residues . The predictive value of a negative test result was 95% . The LAL-test is considered to constitute a valuable cow-side test for the veterinary practitioner, aiding the selection of antibacterial drug of choice for the initial treatment of clinical mastitis.

Probl Tuberk, 1994, (3), 56 - 9
{Characteristics of non-tuberculous Mycobacterium -- pathogens of diseases in man}; Otten TF; The paper characterizes nontuberculosis mycobacteria (NTMB) by their species, shows the structure of mycobacteriasis pathogens, drug sensibility in NTMB and the degree of their virulence for laboratory animals . The specific proportion of NTMB is Mycobacterium avium (50.8%) . A total of 136 cases of mycobacterium infection were examined . As high as 20.7% of isolates from mycobacteriasis patients have been found to have a high natural resistance to most antibacterial drugs . A combination of kanamycin, ethionamide, and ethambutol is the most effective in the treatment, additionally aminoglucosides--amikacin, gentamicin, sulfamides, such as biseptol, sulfadimethoxin, as well as the quinolones ciptobay and tarivid.

Acta Microbiol Immunol Hung, 1994, 41(1), 33 - 9
Competition between dopamine, beta-receptor agonists and promethazine in Escherichia coli plasmid replication; Molnar J et al.; The substrates in the phenylalanine, metabolism play key roles in the physiological processes of bacteria . Promethazine affects the phenylalanine metabolism in Escherichia coli . The antibacterial and anti-plasmid actions of promethazine were prevented by phenylalanine, tyrosine, phenylpyruvic acid, phenylacetic acid, noradrenaline and dopamine in minimal medium . Isoproterenol (and phenoxybenzamine) reduced, while propranolol, oxyprenolol and alprenolol isomers enhanced the anti-plasmid effect of promethazine . Propranolol itself induced an anti-plasmid effect . The effects of beta-receptor agonists and antagonists on promethazine-induced anti-plasmid action serve as an indirect evidence of beta adrenergic like binding sites in E . coli . These binding sites are involved in the plasmid replication process and are connected with promethazine binding sites in bacteria.

Akush Ginekol (Mosk), 1994, (6), 33 - 7
{Evaluation of the effects of methods of suppurative-inflammatory complications prevention after cesarean section on cellular and humoral components of the immune system}; Chernukha EA et al.; The immune status of 73 pregnant women and puerperae, administered proteolysis inhibitors or common antibacterial therapy to prevent pyoseptic complications, was assessed before cesarean section and 1 and 7 days after it . The results indicate certain shifts in the immunity status of puerperae of all groups, which were the most expressed 1 day after surgery (reduced content of CD3 lymphocytes, IgG and IgA, and a marked increase of the content of C-reactive protein) and normalized by day 7 postoperation . These changes are most likely to be caused by the surgical intervention but not the infectious inflammatory process, which is proved by the absence of pyoseptic complications after prophylactic measures taken . Hence, proteolysis inhibitors, along with the traditional methods, may be recommended for the prevention of pyoseptic complications after cesarean section.

J Biomater Sci Polym Ed, 1994, 6(6), 533 - 9
A comparison between the hemolytic and antibacterial activities of new quaternary ammonium polymers; Marchisio MA et al.; New quaternary ammonium polymers, which in a previous work had shown relevant antibacterial properties, have been investigated as regards to their hemolytic activity (HA) in comparison with a low molecular weight commercial antibacterial agent, Steramine G (SG) . All polymers exhibit negligible, or at most modest, HA at dosages and contact times at which SG is strongly hemolytic.

Probl Tuberk, 1994, (5), 40 - 3
{Effects of antibacterial preparations on growth of Mycobacterium tuberculosis in a model of primary tuberculous infection in tissue culture}; Kunichan AD et al.; Bactericidal activity of isoniazid, rifampicin and pyrazinamide in different regimens was studied on 120 mouse lung explants infected with H37Rv M . Tuberculosis . An increase in isoniazid concentration and duration of the exposure entails enhancement of its bactericidal activity . A direct correlation exists between the concentration and the exposure . Rifampicin is active mainly within first 30 minutes of its contact with the infected tissue without further augmentation of bactericidal activity with increasing concentrations and exposure . Pyrazinamide bactericidal activity is not high . Its enhancement depends rather on increasing concentrations than on duration of the exposure.

Probl Khig, 1994, 19, 88 - 96
{Granulocyte alkaline phosphatase--a biomarker of chronic benzene exposure}; Khristeva V et al.; In tracing the cellular population status in the peripheral blood of workers, exposed to benzene, was included and cytochemical determination of the alkaline phosphatase activity in leucocytes . This enzyme is accepted as marker of the neutrophilic granulocytes, as maturation of the cells and their antibacterial activity are parallel to the cytochemical activity of the enzyme . 78 workers from the coke-chemical production from state firm "Kremikovtsi" and 41 workers from the production "Benzene" and "Isopropylbenzene"--Oil Chemical Plant, Burgas are included . The benzene concentrations in the air of the working places in all productions are in the range of 5 to 50 mg/m3 . For cytochemical determination of the alkaline phosphatase activity is used the method of L . Kaplow and phosphatase index was calculated . It was established that in 98.4% of all examined the alkaline phosphatase activity is inhibited to different rate, as from 46.5% {61 workers} it is zero . In considerably lower percentage of workers were established and other deviations: leucocytosis or leucopenia, neutropenia, increased percent of band neutrophils and toxic granules . The results of the investigation of the granulocyte population show that from all indices, the activity of granulocyte alkaline phosphatase demonstrates most convincing the early myelotoxic effect of benzene.

Chemotherapy, 1994, 40(6), 412 - 7
Levofloxacin, an optical isomer of ofloxacin, has attenuated epileptogenic activity in mice and inhibitory potency in GABA receptor binding; Akahane K et al.; The combination of some new quinolone antibacterials with 4-biphenylacetic acid (BPAA) functionally inhibits the gamma-amino-butyric acid (GABA) receptors and thereby induces clonic convulsions . We examined the effects of ofloxacin and its optical isomers on this quinolone-induced neurotoxicity . Norfloxacin at 10(-5) M alone or at 10(-7) M in combination with BPAA (10(-4) M) inhibited {3H}muscimol binding to rat brain synaptic membranes . Ofloxacin and its optical isomers did not affect muscimol binding by themselves . While they slightly reduced muscimol binding at 10(-4) M in combination with BPAA, the inhibitory activity of the l-isomer levofloxacin (DR-3355) on muscimol binding was slightly, but significantly, weaker than that of the d-isomer DR-3354 and ofloxacin . Intracisternal injection of norfloxacin (5 micrograms), ofloxacin, levofloxacin or DR-3354 (50 micrograms each) induced clonic convulsions in mice . The incidence of these convulsions was enhanced by the combination with BPAA (50 micrograms) . The epileptogenic activity of levofloxacin was also weaker than that of DR-3354 or ofloxacin when quinolones were given alone or in combination with BPAA . These results suggest that epileptogenic activity of quinolones is closely related to the inhibitory potency in GABA receptor binding and that levofloxacin may have lower neurotoxicity than ofloxacin and DR-3354.

Magy Traumatol Ortop Kezseb Plasztikai Seb, 1994, 37(4), 301 - 3
{Prophylactic use of Zinacef in orthopedics}; Gyetvai A et al.; Authors give a brief summary on necessity of antibiotic prophylaxis in orthopaedics, pointing out the hip, knee arthroplasty and the spinal fusion with Steffee plate . They introduce the applied antibiotic, called Zinacef and it's antibacterial spectrum and the way in prophylaxis is discussed . No any septic complication was observed out of one thousand surgical interventions.

Prog Clin Biol Res, 1994, 388, 41 - 51
The bactericidal/permeability increasing protein of neutrophils is a potent antibacterial and anti-endotoxin agent in vitro and in vivo; Elsbach P et al.; The Bactericidal/Permeability Increasing protein (BPI) is a major constituent of the azurophilic granules of human and rabbit polymorphonuclear leukocytes (PMN) . The cDNA of the highly conserved protein has been isolated from man, rabbit and cow . The ca . 50 kDa BPI and a ca . 25 kDa bioactive N-terminal fragment are cytotoxic only for Gram-negative bacteria (GNB) . This target-cell specificity reflects the strong attraction of the highly cationic protein for the negatively charged lipopolysaccharides (LPS) in the bacterial envelope . Native and recombinant (r) holo-BPI and the N-terminal fragment (rBPI-23) bind with high affinity (apparent Kd 1-10 nM) to all forms of isolated LPS so far examined, and inhibit the numerous biological effects of LPS in vitro (including in whole blood ex vivo) as well as in animals . Under the same conditions the antibacterial activities of holo-BPI and rBPI-23 against GNB with rough chemotype LPS are the same, but against serum-resistant and smooth chemotype GNB rBPI-23 is up to 30-fold more potent than holo-BPI . Holo-BPI and rBPI-23 protect mice, rats and rabbits against lethal cytotoxic effects of LPS and in some cases against lethal inoculations with live GNB.

Prog Clin Biol Res, 1994, 388, 147 - 59
Endotoxin-binding synthetic peptides with endotoxin-neutralizing, antibacterial and anticoagulant activities; Hirata M et al.; Endotoxin(lipopolysaccharide = LPS), cell wall component of gram-negative bacteria, activates monocytes and macrophages to release cytokines, reactive nitrogen intermediates (RNI), and to generate tissue factor(TF) which initiate coagulation . We have purified 7kDa and 18kDa cationic antibacterial proteins (CAP-7 and CAP-18) with LPS-binding and LPS-neutralizing activities from rabbit granulocytes using as an assay the agglutination of erythrocytes coated with Re-LPS . From protein sequencing, CAP-7 was identified as the C-terminal 37 amino acid fragment of CAP-18 . Synthetic peptide #197 (identical sequence to CAP-7, Gly1-Try37) and #36-1 (a truncation of CAP consisting of 32 amino acid residues, Gly1-Ala32) showed LPS-binding activity . Each peptide inhibited LPS-induced tissue factor(TF) generation by murine peritoneal macrophages, even added 1-3 hours after stimulation of cells with LPS . C57BL/6 mice treated with #197 were significantly protected from lethal LPS challenge . Peptide #36 also blocked the LPS-induced lethality . These peptides had antibacterial activity to gram-negative bacteria, such as E.coli, S.typhimurium, K.pneumonia, Ps.aeruginosa and also to gram-positive S.aureus (Methicillin sensitive and resistant strains) . Both peptides inhibited TF- and Xa-induced plasma clotting . Using synthetic chromotogenic substrates, both CAP7 peptides blocked the coagulation cascade at two sites, activation of factor X to Xa and conversion of Factor II (prothrombin) to factor IIa (thrombin) . In vivo treatment of peptide #197 prevented acute lethality in mice injected with tissue factor (rabbit brain thromboplastin) . Two other peptides, #32(Gly1-Phe9) and #50(Ile13-Typ37) failed to demonstrate LPS-binding, LPS-neutralizing, antibacterial and anticoagulant activities . The active peptides but not the inactive peptide maintain a putative heparin binding domain at their N-termini . This heparin binding domain is participate in the LPS-binding, LPS neutralizing, antibacterial and anticoagulant activities of CAP7 . These active peptides may have a therapeutic potential for treatment for DIC due to sepsis and endotoxin shock.

Zentralbl Chir, 1994, 119(10), 714 - 21
{Change in the treatment method of infected pseudarthrosis with bone loss of the tibia}; Schultz JH et al.; AIM OF INVESTIGATION: The treatment of nonunions complicated by infection and bone loss is divided into two stages . Having calmed down the infection by stabilizing, removal of infected and necrotic tissue and local antibacterial measures, the bone loss has to be filled up . Bridging the gap by means of autogenous cancellous bone grafting is complicated by a high rate of refractures depending on the length of bone loss . Therefore after changing the method and using the Ilizarov procedure it is of interest, whether this method offers advantages . Our experience is to be reported and discussed . METHODS: According to the clinical course two groups of patients with nonunions of the tibia complicated by infection and bone loss were compared . 25 previously evaluated patients of the years 1980/81 whose tibial bone loss was bridged by cancellous bone grafting (1st group) were compared with 16 patients who were treated by the Ilizarov method from May 1990 to October 1993 (2nd group) . The average age was nearly the same (32.6/32.9 years) . In the first group the average of bone loss measured 4 cm, in the second 7.8 cm . The number of initial operations to eliminate infection and the duration of fixator application from the beginning of bridging bone loss were compared as well as early and late complications, especially the rate of refracture and reinfection . RESULTS: 1.2 operations were needed to eliminate infection in the first group, in the second only one was necessary . The handling of the Ilizarov device is more difficult and needs training . The higher rate of early complications at the beginning decreased with increasing experience . The average of fixation time could be reduced by about ten days per cm of bone loss using the Ilizarov technique . By segmental transport new cortical bone is generated which surpasses cancellous bone grafting in regard to stability . This seems to be an important reason that refracture did not occur in the second group . Furthermore, reinfection could be avoided up to now obviously due to sufficient segmental resection of infected and necrotic tissue . Limited stores of autogenous cancellous bone are not to be feared . The total number of operations can be reduced . At the docking side early single cancellous bone grafting is recommended.

Klin Khir, 1994, (4), 28 - 30
{Combined endolymphatic therapy in patients with diffuse peritonitis}; Sheremet PF et al.; The results of treatment of 25 patients with diffuse peritonitis whom the combined endolymphatic therapy was conducted in postoperative period, including the lymph irradiation with helium-neon laser and direct endolymphatic antibacterial therapy, are presented . Catheter was used introduced in peripheral lymph vessel on the dorsal surface of foot . The decrease of organism intoxication, more rapid than in control, was noted.

Int Ophthalmol, 1994-95, 18(4), 221 - 4
Aqueous penetration of orally administered ciprofloxacin in humans; Gulati VK et al.; The aqueous penetration of orally administered Ciprofloxacin (CPX) was studied in twenty-two human volunteers undergoing cataract surgery . CPX in a dose of 250 mg, was given p.o . at 12 hourly intervals in 3 groups such that a maximum dose of 0.5 grams was delivered in one group, 1.0 grams in another and 1.5 grams in the last group . A fourth group consisted of 6 individuals who were controls and received lactose tablets . Twelve hours after the last dosing aqueous samples were collected and assayed by the Grove-Randall technique . The aqueous penetration of Ciprofloxacin achieved was 1.51 +/- 0.15 mgL-1 in group II and 2.49 +/- 0.52 mgL-1 in group III . In group I, the aqueous concentration was experimentally indeterminate and the control samples in group IV did not show any antibacterial activity . Divided oral doses of 1.5 grams of CPX were found to produce an aqueous titre up to 2.5 times the MIC of Ps . aeruginosa.

Ciba Found Symp, 1994, 186, 176 - 87; discussion 187-9
Bactericidal permeability-increasing protein in host defence against gram-negative bacteria and endotoxin; Elsbach P; The bactericidal permeability-increasing protein (BPI) is a highly conserved host-defence molecule produced and stored by myeloid cells only and a major constituent of the primary granules of human and rabbit polymorphonuclear leukocytes . The c . 50 kDa BPI and a c . 23 kDa bioactive N-terminal fragment are cytotoxic only for Gram-negative bacteria . This target-cell specificity reflects the high affinity (apparent Kd: 1-10 nM) of BPI for the lipid A portion of lipopolysaccharide (LPS or endotoxin) . Native and recombinant (r) holo-BPI and the N-terminal fragment (rBPI-23) bind with equal affinity to all forms of isolated LPS examined and inhibit the numerous biological effects of LPS in vitro (including in whole blood ex vivo) as well as in animals . Under the same conditions the antibacterial potencies of holo-BPI and rBPI-23 against Gram-negative bacteria with rough chemotype LPS (whether encapsulated or not) are also the same, but against more resistant smooth chemotype Gram-negative bacteria rBPI-23 is up to 30-fold more potent than holo-BPI . Holo-BPI and rBPI-23 protect a broad range of animals against lethal cytotoxic effects of LPS and in some cases against lethal inoculations with live Gram-negative bacteria.

Ciba Found Symp, 1994, 186, 140 - 51; discussion 151-9
Antibacterial peptides in insect vectors of tropical parasitic disease; Ham PJ et al.; The induction and characterization of immune peptides in two groups of medically important insects, the mosquitoes and blackflies, is currently an important research area . Mosquitoes transmit a variety of viral and parasitic diseases including yellow fever, dengue, malaria and lymphatic filariasis . Simuliid black flies are vectors of river blindness . The diseases are together responsible for death and morbidity in millions of people each year . The relationship between inducible peptides and bacterial and parasitic infections in these insects is proving to be a complex one . The identification of an insect defensin (4 kDa) in Aedes aegypti, the yellow fever mosquito, has proved to be the first peptide characterized in a vector of human disease . This inducible molecule appears in the haemolymph in response to bacterial and to a lesser extent filarial infection . The characterization of inducible blackfly peptides has revealed potent inducible anti-Gram-positive as well as anti-Gram-negative activity . In addition, non-self recognition molecules such as phenoloxidase may play a part in differentiating one species of eukaryotic pathogen from another of the same genus . The interactions between the peptides and these other proteins are likely to be important in the establishment of a successful immune response against a parasitic pathogen, particularly as we now know these peptides to have anti-eukaryotic activity (against a range of parasite species) . As well as being of fundamental interest in our understanding of host-parasite relationships, the indication that antibacterial peptides are toxic to parasitic organisms has implications for their possible use in the disease vector control strategies of the future . It may also mean that a revision in our understanding of their mode of action, loose as it is, has to take place.

Ciba Found Symp, 1994, 186, 107 - 19; discussion 120-2
Drosophila as a model system for antibacterial peptides; Hultmark D; As a defence against bacteria, infected insects synthesize cecropins and a large number of other bactericidal proteins and peptides . To understand this response and its possible relationship with similar systems in mammals, we need to characterize the induced components and how they act, as well as how this antibacterial response is initiated . To study the molecular basis for this response we cloned the genes for cecropins and other bactericidal peptides from Drosophila, 14 genes in total . The cecropin genes were selected as convenient markers for the immune response because they are strongly induced by different microbial substances . In contrast the lysozyme gene family is constitutively expressed in the digestive tract . We have developed an inducible blood cell line from Drosophila for studying the immune response in vitro . Using this system we are now investigating the function of membrane proteins and signal pathways in the transcriptional activation of immune genes in Drosophila.

Adv Exp Med Biol, 1994, 357, 219 - 26
Physicochemical and antibacterial properties of lactoferrin and its hydrolysate produced by heat treatment at acidic pH; Saito H et al.; In order to apply functionally active lactoferrin (Lf) to food products, the effect of pH on the heat stability of Lf was studied . Lf was easily denatured to an insoluble state by heat treatment under neutral or alkaline conditions, above pH 6 . In contrast, it remained soluble after heat treatment under acidic conditions at pH 2 to 5, and the HPLC pattern of Lf heat-treated at pH 4 at 100 degrees C for 5 min was the same as that of native Lf . Lf was found to be very thermostable at pH 4, and could be pasteurized or sterilized without any significant loss of its physicochemical properties . Lf was hydrolyzed by heat treatment at pH 2 to 3 at above 100 degrees C, and its iron binding capacity and antigenicity were lost . But the antibacterial activity of the hydrolysate was found to be much stronger than that of native Lf . The antibacterial component of Lf hydrolysate produced by heat treatment at acidic pH was verified to be a peptide including the sequence of residues 1-54 from the N-terminal end of the bovine Lf molecule.

Biotechnology, 1994, 26, 247 - 66
Mechanism-based screens in the discovery of chemotherapeutic antibacterials; Kadam S; Numerous assays have been developed over the last 40 years for the detection of novel antibacterial metabolites . I have discussed many of the successful strategies and suggested some potential targets . Although the trend toward mechanism-based assays is relatively recent, it is clear that they have had a profound impact on screening in drug discovery . Often a mechanism-based assay requires construction of specific strains and verification of the antibacterial role of the selected target . Since the conception and development of a mechanism-based screen depends upon knowledge of the specific target and perhaps a compound that affects that target, it is implicit that mode of action studies on compounds discovered through random screening may subsequently lead to new mechanistic assays . While serendipity continues to play a crucial role in any screen, target-directed assays appear to be a worthwhile approach in antibacterial screening.

Ophthalmic Res, 1994, 26(6), 344 - 51
Nontoxic intravitreal dose of ofloxacin for rabbit retina; Sakai H et al.; We studied the nontoxic intravitreal concentration of ofloxacin, a new quinolone antibacterial agent, by evaluating its effects on in vitro and in vivo electroretinograms (ERGs) in albino and pigmented rabbits . After perfusion with a 36 micrograms/ml solution of ofloxacin, the in vitro ERG remained unchanged . The in vivo ERG and the visually evoked potential remained unchanged 4 weeks after vitrectomy with 50 micrograms/ml ofloxacin, and the retina was within normal limits both ophthalmoscopically and histologically . Therefore, the retinal toxicity of ofloxacin is low and within safe limits at clinical dosage.

Klin Khir, 1994, (11), 13 - 5
{Intraoperative ultrasonic treatment in suppuration of necrotic foci of the pancreas and retroperitoneal tissue}; Bagdasarov VV et al.; Of 312 patients with an acute pancreatitis the purulent complications have occurred in 33 (10,8%) . The low-frequency ultrasound was applied by the authors in 14 patients for sanation of abscesses . There were no complications . Antibacterial effect of the low-frequency ultrasound was revealed . The combined method with kanamycin application and the rational drainage is recommended for wide introduction in clinical practice.

Klin Khir, 1994, (3), 34 - 6
{The efficacy of the clinical use of the preparation Cifran in treating surgical infection}; Datsenko BM et al.; The results of the use of antibacterial preparation "Cifran" in patients with purulent-inflammatory processes of different genesis and location were studied . A good tolerance of the patients to the preparation was established . High chemotherapeutic effectiveness of the preparation in detection of gram-positive, gram-negative and anaerobic microflora was noted.

Klin Khir, 1994, (11), 23 - 5
{Use of intra-tissue electrophoresis and electrophonophoresis in the multimodal treatment of edematous forms of pancreatitis}; Alekseenko AV et al.; The experience of treatment of 305 patients with the edematous++ forms of pancreatitis is assigned . The application efficacy of intra-tissue (pancreatic) electrophoresis and electrophonophoresis using inhibitors, cytostatics, antibacterial and the other medicinal agents was studied . Decrease of frequency of the destructive pancreatitis appearance and the treatment results improvement were promoted by application of the intra-tissue electrophonophoresis with the chemotherapeutic agents in the complex treatment of an acute or exacerbated pancreatitis.

J Enzyme Inhib, 1994, 8(1), 25 - 37
Antibacterial effects of esters of guanidino- and amidino-acids trypsin inhibitors; Kato M et al.; Inhibitory effects of various esters of trans-4-guanidinomethylcyclohexanecarboxylic acid and the 4-tert- butylphenyl esters of amidinopiperidine-4-alkanoic, trans-4- amidinocyclohexanealkanoic, trans-4-guanidinoethylcyclohexanecarboxylic and trans-4-guanidinocyclohexanealkanoic acids, all trypsin inhibitors, on the growth of E . coli, B . subtilis, S . aureus and S . epidermidis were examined . 4-tert-Butylphenyl esters strongly inhibited the growth of E . coli and the order of the inhibitory effects correlated with that for the inhibitory effects on proteinase In, which appears immediately before initiation of DNA synthesis in E . coli and closely correlates with the onset of DNA synthesis . No correlation was observed between the inhibitory effects and Ki values for trypsin . The 4-tert-butylphenyl esters also strongly inhibited B . subtilis, S . aureus and S . epidermidis, and the order, of the inhibitory effects on these bacteria roughly coincided with that on E . coli . The order of the inhibitory effects of each ester, on these bacteria was S . epidermidis > S . aureus > B . subtilis > E . coli . Among the esters examined, the biphenyl ester of trans-4-guanidinoethylcyclohexanecarboxylic acid was the most inhibitory on these four bacteria and proteinase In . Hydrolysis of tert-butyloxycarbonyl-L-valyl-L-prolyl-L-arginine 4-methylcoumarin-7-amide, which is a substrate for proteinase In, in crude extracts of E . coli, B . subtilis and S . epidermidis was examined . The order of this activity in these bacteria was E . coli > B . subtilis > S . epidermidis.

Tsitologiia, 1994, 36(11), 1102 - 12
{The comparative characteristics of the immunogenic and immunomodulating activity of different antigenic preparations of the causative agent of Q fever Coxiella burnetii}; Tokarevich NK et al.; The immunogenicity of the Coxiella burnetii corpuscle antigen and two its components, obtained after the treatment with chloroform-methanol or extraction by trichloroacetic acid, was investigated . All the studied antigens were highly immunogenic . A strong correlation was discovered between the immunogenic and immunomodulating properties of the C . burnetii antigens . Cells of the mononuclear phagocytic system are the targets for stimulating action of the studied antigens . A cyclic increase of antibacterial activity and oxygen-dependent metabolism of the peritoneal cells was noted, in addition to the increase of the natural splenocyte cytotoxicity caused by the action of these antigens . The role of cytokines in rising the activity of peritoneal cells and splenocytes, caused by immunization of mice with the above antigenic substances, is discussed.

Eur J Cancer, 1994, 30A Suppl 3, S34 - 9
The changing face of stem cell transplantation by the use of recombinant human granulocyte colony stimulating factor; Boogaerts MA et al.; The use of peripheral blood progenitor cells (PBPC) for autografting following high-dose chemotherapy in a variety of malignancies has increased markedly with the advent of efficacious and safe myeloid growth factors, which have dramatically improved collection yields . There is still controversy as to whether PBPC should be harvested after a combination of chemotherapy and growth factors, or after growth factors alone . The use of powerful combinations of newer growth factors, such as interleukin-3 with granulocyte-macrophage colony stimulating factor (GM-CSF), or granulocyte colony stimulating factor (G-CSF) with stem cell factor, may obviate the need for chemotherapy . The problem of providing sufficient numbers of PBPC for successful transplantation and sustained engraftment has led to the development of a variety of in vitro expansion systems for stem cells, using cocktails of growth factors . Single blood collections may contain sufficient CD34+ cells to be expanded on a large scale for clinical transplantation, eliminating costly and labour intensive apheresis procedures . PBPC transplants may carry less risk for contamination with malignant cells; however, sensitive detection techniques have revealed that tumour cell contamination of PBPC harvests may be much more prevalent than was previously suspected and both positive and negative selection of CD34+ cells for clinical transplantation is being investigated . PBPC transplantation generally results in more rapid engraftment, with faster recovery of neutrophils and platelets, compared with autologous bone marrow transplants . In most studies, PBPC transplants also resulted in fewer septic episodes, fewer intensive care admissions, fewer transfusions of red blood cells and platelets, reduced antibacterial and parenteral nutrition use, and reduced hospital costs . Dose optimisation and intensification of chemotherapy, relying on repeated administration of growth factor-mobilised PBPC, offers interesting prospects in the treatment of a variety of tumours . However, well-controlled, randomised prospective trials will be needed to prove the real value of PBPC transplants with regard to survival and cure . In the clinical setting, PBPC transplantations are likely to replace autologous marrow transplants in the near future . Manipulation of PBPC in vitro, i.e . expansion or gene transfer, may prove to be the most exciting perspective in the treatment of both malignant and non-malignant haematological conditions.

Vestn Ross Akad Med Nauk, 1994, (8), 29 - 33
{Pathogenetic rationale and basic principles in the comprehensive detoxifying therapy of purulent peritonitis}; Gostishchev VK et al.; The multimodality therapy for patients with purulent peritonitis and Degrees II-III endotoxicoses involves efferent methods of detoxification and hemocorrection alone and in combinations with hemosorption (HS), plasmapheresis (P), ultraviolet autoblood radiation (UVAR), immunocorrection through extracorporeal donor xenosplenic inclusion (EDXSI) or xenoperfusate infusion (XPI), indirect electrochemical detoxification (IECD) of blood and exfused plasma by the use of sodium hypochlorite (NaClO) obtained on an EDO-1 electrochemical unit . The analysis of therapeutical results has indicated that the efferent methods should be included into the multimodality therapy only in Degrees II-III endotoxicoses when a considerable number of toxic components leading to the development of organ- and system-specific insufficiency accumulate in the patients' circulatory systems . With this, the obligatory conditions are an adequate sanitation of the abdomen with the topical application of NaClO as an antiseptic and a fibrinolytic, rational antibacterial and homeostatic corrective therapy . The combined use of the efferent methods (HS+UVAR; HS+XPI; P+IECD of plasma) in the programmed mode is pathogenetically grounded, which produces a potentiating detoxifying effect, and levels the negative aspects of each method alone . P is preferable when it is used alone (in case of adequate plasma replacement . A comprehensive therapy policy has been developed in accordance with the stage of peritonitis and the degree of endotoxicosis.

Life Sci, 1994, 54(1), PL5 - 9
Anti-HIV effect of gramicidin in vitro: potential for spermicide use; Bourinbaiar AS et al.; Gramicidin, cation channel forming ionophore with antibacterial properties, was studied in vitro for inhibition of human immunodeficiency virus (HIV) infection of MT-4 lymphocytes . Effective antiviral concentrations required for complete HIV inactivation were three orders of magnitude lower than 10 micrograms/ml cytotoxic dose . Gramicidin, routinely used as a contraceptive agent, should be considered for clinical application as a spermicide with antiviral activity.

Gene, 1993 Dec 27, 137(1), 7 - 11
The broad utility of soluble peptide libraries for drug discovery; Houghten RA; The use of soluble peptide combinatorial libraries made up of millions, billions, or now even trillions (10(6), 10(9) and 10(12)) of peptides, currently used in a wide range of investigations, is discussed . These include: antibody/peptide antigen studies, the development of new ligands through the use of radio receptor assays, novel enzyme inhibitors, antibacterial and antifungal peptides through the use of microdilution assays, antivirals in plaque assays, and cardiovascular drugs in in vivo studies . The use of a new positional scanning library composed of approximately four trillion decapeptides is illustrated in a radio receptor assay . The criteria by which libraries, in general, can be judged will be described.

FEBS Lett, 1993 Dec 27, 336(2), 284 - 8
Molecular cloning of a putative homolog of proline/arginine-rich antibacterial peptides from porcine bone marrow; Pungercar J et al.; Screening of a porcine bone marrow cDNA library with a PCR-derived probe from rabbit LPS-binding protein CAP18 led to the discovery of two closely related clones . The longer, full-length cDNA clone encodes a 228 amino acid residue protein similar to the family of antibacterial/LPS-binding cationic peptides . In contrast to other hitherto discovered precursors of Pro/Arg-rich peptides from this family, they have a novel, unique structure of the C-terminal region of 100 amino acid residues with a repeating sequence of ten residues (FPPPNXPGPR, where X = V or F) . These precursors could represent a part of the antibacterial peptide repertoire of porcine bone marrow.

Biochem Biophys Res Commun, 1993 Dec 15, 197(2), 508 - 17
Insect immunity: the diptericin promoter contains multiple functional regulatory sequences homologous to mammalian acute-phase response elements; Georgel P et al.; We are using the diptericin gene as a model system to study the control of expression of the genes encoding antibacterial peptides during the Drosophila immune reaction . In order to investigate the putative regulatory regions in the diptericin promoter, we performed DNaseI footprinting experiments combined with gel-shift assays in two inducible systems: the larval fat body and a tumorous Drosophila blood cell line . Our results confirm the importance of kappa B-like elements previously described in the immune response of insects and reveal for the first time the involvement of other regions containing sequences homologous to mammalian acute-phase response elements.

Pharmacoeconomics, 1994, 5(Suppl 2), 40 - 3
Cost-effectiveness opportunities for new antibiotics; Hillman A; Antibacterial drugs account for between 6 and 21% of the drug market in various countries, or between 3 and 25% of the total prescriptions . Given the high usage of these agents, they are appropriate candidates for economic appraisal in the near future . It is probable that the marketplace and healthcare reform will give managed care the dominant position in the US healthcare system . Cost-effectiveness analyses of managed care organisations are based on both hospital and outpatient costs, and they are increasingly being aimed at formulary decisions regarding pharmaceuticals . Appropriate outcome parameters, long term follow-up, and phase IV trials to determine costs and outcomes relating to actual clinical use are needed to assess cost-effectiveness . Unbiased pharmacoeconomic research is needed to accurately answer questions on the economic viability of new products, and to avoid scepticism on the part of the purchasers of healthcare . The ultimate challenge for research and development of new antibiotics will be to reconcile the needs of the patient with the economic needs of society, within the cost-effectiveness paradigm.

Pharmacoeconomics, 1994, 5(Suppl 2), 20 - 6
Cost-effectiveness and value of an IV switch; Jewesson P; A few antibiotics (i.e . metronidazole, clindamycin and ciprofloxacin) are available in both parenteral and oral formulations, and have good bioavailability, ensuring equivalent systemic drug concentrations . During a 4-year period subsequent to the initiation of a parenteral to oral (IV-PO) stepdown programme for metronidazole and clindamycin, Vancouver General Hospital saved approximately $C85 000 . However, many parenteral antibacterials lack an oral formulation, requiring oral stepdown to a different antibacterial with a similar spectrum of activity . Alternatively, the oral formulation of a parenteral antibacterial may have poor bioavailability (i.e . cefuroxime axetil, ampicillin, cloxacillin, erythromycin, and tetracycline) and it is not possible to maintain equivalent systemic drug concentrations . While rigid criteria are not applicable to all clinical scenarios, the general criteria for oral stepdown include the following: the patient 1) continues to need an antibiotic; 2) is clinically stable; 3) is capable of tolerating the oral dosage form; and 4) has no factors present (e.g . gastrointestinal abnormalities or drug interactions) that would adversely affect oral bioavailability . A review of subsequent IV-PO stepdown programmes at Vancouver General Hospital revealed that 1) not all patients receiving parenteral therapy are candidates for oral stepdown; 2) oral stepdown is delayed in a large proportion of treatment courses; 3) oral stepdown is not occurring in many patients for whom it is deemed appropriate; and 4) in a very few treatment courses stepdown may occur prematurely and may contribute to clinical deterioration.(ABSTRACT TRUNCATED AT 250 WORDS)

Gene, 1993 Dec 8, 134(2), 241 - 3
Sequences of two cDNA clones from the medfly Ceratitis capitata encoding antibacterial peptides of the cecropin family; Rosetto M et al.; Using a back translated oligodeoxyribonucleotide probe, encoding a conserved motif in insect antibacterial peptides, we have isolated two cDNA clones from the medfly, Ceratitis capitata . Sequence determination shows that the cDNAs encode two closely related peptides which are members of the cecropin family.

J Chromatogr A, 1993 Dec 3, 655(2), 177 - 84
Influence of the chromatographic capacity factor (log k') as an index of lipophilicity in the antibacterial activity of a series of 6-fluoroquinolones . Relationship between physico-chemical and structural properties and their hydrophobicity; Martorell C et al.; The aim of this study was to establish the influence of lipophilicity on the antibacterial activity (log 1/MIC50) of 22 fluoroquinolones and to assess the influence of their electronic, steric and topological properties on their hydrophobicity . The lipophilicity of the compounds, expressed as the chromatographic capacity factor (log k'), was determined by ion-pair reversed-phase HPLC . On the basis of the mathematical models developed, an attempt was made to confirm the mechanism of interaction of the quinolones with DNA-gyrase proposed previously.

Vet Clin North Am Equine Pract, 1993 Dec, 9(3), 481 - 91
Pharmacokinetic values of drugs frequently used in performance horses; Dyke TM; Tables of values of pharmacokinetic variables (volume of distribution, total body clearance, and plasma elimination half-life) of drugs frequently administered to performance horses are accompanied by explanatory notes . Drugs described include the nonsteroidal anti-inflammatory drugs, corticosteroids, anabolic steroids, central nervous system-modifying drugs, respiratory system drugs, diuretics, local anesthetics, and antibacterial drugs.

J Antibiot (Tokyo), 1993 Dec, 46(12), 1866 - 82
Heteroaryliumthio substituted carbapenem derivatives: synthesis and in vitro activity of 1 beta-methyl-2-(dihydropyrrolotriazoliumthio)carbapenems; Wildonger KJ et al.; The syntheses of five thiols, including three dihydropyrrolotriazoliumthiol salts, 1,4-dimethyl-5-mercaptomethyl-1,2,4-triazolium trifluoromethanesulfonate, and 6-mercapto-6,7-dihydro-5H-pyrazolo{1,2-a}{1,2,4}triazolium chloride; and the addition of these thiols to 4-nitrobenzyl (1R,5R,6S)-2-(diphenylphosphono)oxy-6-{1(R)-hydroxyethyl}-1-met hylcarbapen-2-em-3-carboxylate and the subsequent hydrogenolysis of the addition products is described . The latter thiol provides a new route towards the preparation of L-627 (LJC 10,627) . The compounds were evaluated in vitro against a panel of Gram-positive and Gram-negative bacteria and their antibacterial activities compared with imipenem . The compounds were measured for their hydrolytic stability to dehydropeptidase I (DHP-I) relative to imipenem . The five compounds generally had poorer Gram-positive and Pseudomonas activity than imipenem, although their Gram-negative activity was variably improved . The monocyclic triazolium analog was nearly comparable in overall activity to the four bicyclic heterarylium analogs evaluated, including L-627 (LJC 10,627) . All compounds were more stable to DHP-I than imipenem, although minor differences existed among them.

Nurs Clin North Am, 1993 Dec, 28(4), 911 - 9
Issues in the management of percutaneous central venous catheters . Single and multiple lumens; Orr ME; In this era of high technology and extensive parenteral therapies, multiple-lumen CVCs seem to be among the many devices needed to provide appropriate care to hospitalized patients . All CVCs, regardless of their benefit, create substantial risks for mechanical and septic complications . Antibacterial solutions that are bonded to the catheter and longer-acting skin antiseptics offer preliminary evidence that CVC sepsis rates can be reduced . The advances in CVC design, materials, and coatings are intended to be a supplement to--not a substitute for--meticulous care of CVCs.

J Chemother, 1993 Dec, 5(6), 543 - 5
Efficacy and tolerability of brodimoprim in pediatric infections; Careddu P et al.; Brodimoprim is a long acting broad spectrum antibacterial agent . It is a new selective inhibitor of bacterial dihydrofolate reductase, structurally related to trimethoprim . The aim of the present study was to investigate the efficacy and tolerability of brodimoprim (10 mg/kg on the first day, 5 mg/kg/die onward) in the treatment of upper respiratory tract infections in children (age range: 2-14 years) . This open group comparative study was performed either in 68 children affected by bacterial pharyngotonsillitis (37 treated with brodimoprim, 31 with erythromycin 560 mg/kg/8 hours) or in 50 patients affected by otitis media (25 treated with brodimoprim, 25 with amoxicillin/clavulanic acid 50 mg/kg/12 hours) or in 52 patients affected by acute sinusitis (25 treated with brodimoprim, 27 with amoxicillin/clavulanic acid 50 mg/kg/12 hours) . All patients were clinically evaluated before admission, during the trial and 48 hours after the last dose of antibiotic . At the same time blood and secretion samples were collected for hematology/biochemistry and microbiological assays . A total of 170 subjects were treated and 141 patients demonstrated a clinical recovery/improvement following the treatment period, with approximately the same recovery rate (83%) among the groups . The bacteriological response was evaluated in 169 subjects . Eradication of pathogens was documented in 27 subjects treated with brodimoprim and 28 with erythromycin in the pharyngotonsillitis group, in 22 subjects treated with brodimoprim and 16 with amoxicillin/clavulanic acid in the otitis group and in 17 subjects treated with brodimoprim and 20 with amoxicillin/clavulanic acid in the sinusitis group . The overall eradication in brodimoprim treated patients was 77% in comparison with 76% of eradication obtained in the control groups.(ABSTRACT TRUNCATED AT 250 WORDS)

J Chemother, 1993 Dec, 5(6), 507 - 11
Brodimoprim: therapeutic efficacy and safety in the treatment of bacterial infections; Braunsteiner AR et al.; The clinical efficacy and safety of brodimoprim has been studied by numerous investigators . In the trials reviewed 2291 cases were entered . Of these 2214 were evaluable for efficacy and 2277 for safety . Brodimoprim has been found to exhibit good therapeutic efficacy in upper and lower respiratory tract infections, in bacterial gastroenteritis and in typhoid fever . Response rates in the above indications were reported to be in the range of 85-100% for upper respiratory tract infections, 84-92% for lower respiratory tract infections, 97-100% for bacterial gastroenteritis and 95-100% for enteric fever . In controlled studies these response rates were in the same range as those obtained with standard drugs (ampicillin, amoxicillin, cephalosporins, erythromycin, doxycycline, chloramphenicol) . Of the 2277 patients assessable for safety 1429 had received brodimoprim and 848 received a comparative agent . In the brodimoprim group, the overall incidence of clinical adverse events occurring in patients during treatment was 12.7% . The majority of adverse events reported were nausea and vomiting, skin reactions, and CNS reactions . The incidence and pattern of adverse events caused by comparative drugs was similar to those caused by brodimoprim, with the exception of doxycycline which generated fewer clinical adverse events than the other regimens . Brodimoprim in single daily doses may be considered as a highly efficacious and well tolerated antibacterial agent against a broad range of bacterial infections.

J Chemother, 1993 Dec, 5(6), 393 - 9
Basis of selectivity of antibacterial diaminopyrimidines; Baccanari DP et al.; The basis for the high affinity and selectivity of trimethoprim {2,4-diamino-5-(3',4',5'-trimethoxybenzyl)pyrimidine, TMP} and several close structural analogues is reviewed . Methoxy group substitution on the benzyl group of 2,4-diaminobenzylpyrimidine markedly affects both Escherichia coli dihydrofolate reductase (DHFR) Ki values and in vitro antibacterial activity . TMP is several hundred-fold more potent than the unsubstituted benzylpyrimidine, and the monomethoxy and dimethoxy analogues are of intermediate activity . However, equilibrium dissociation constants determined in the absence of cofactor (NADPH) show that the binding of these diaminobenzylpyrimidines in the enzyme-inhibitor binary complex is considerably weaker and does not vary among the compounds . Thus, the TMP binding affinity of E . coli DHFR is increased by NADPH in the ternary complex, and this increased affinity (cooperativity) varies with methoxy group substitution . In contrast, mouse DHFR has a weaker binding affinity for diaminobenzylpyrimidines, and none of the analogues show strong NADPH cooperative effects . The difference in the magnitude of NADPH/TMP cooperativity between bacterial and mammalian DHFR is an important factor in selectivity . The E . coli enzyme binds TMP more avidly in binary complex, and an additional selectivity factor of 30-fold arises from differences in cooperativity . Although the X-ray crystal structures of bacterial and vertebrate DHFR have been studied extensively, no single hypothesis convincingly explains the molecular basis of TMP selectivity . However, information on the three-dimensional structure of the enzyme has been used to rationally design novel, high-affinity inhibitors.

J Chemother, 1993 Dec, 5(6), 377 - 88
Structure-activity relationships of dihydrofolate reductase inhibitors; Bowden K et al.; Structure-activity relationships of antibacterial dihydrofolate reductase inhibitors are reviewed . A short introduction is followed by a more detailed review of developments since 1980 . The design of site directed inhibitors based on data from X-ray crystallographic, NMR spectroscopy and molecular graphic studies is discussed . The development of quantitative structure-activity relations is surveyed from a historical point of view and these are contrasted with more recent alternative approaches . Conclusions are reached regarding possible future developments.

Hua Xi Yi Ke Da Xue Xue Bao, 1993 Dec, 24(4), 349 - 52
{Study on antibacterial proteins from rabbit bladder mucosa}; Wu Q et al.; Acid-soluble extract of rabbit bladder mucosa was obtained by washing out the bladder of normal female New Zealand rabbit with 1% acetic acid in the presence of proteinase inhibitors . Acid urea polyacrylamide electrophoresis (AU-PAGE) analysis indicated that the extract had more than 10 main protein bands . The currently-known antibiotic peptides, e . g . lysozyme and defensin-like molecules were not found in this material . When tested for antibacterial activity by using ultrasensitive radial diffusion assay, the acid-soluble extract effectively killed E . coli ML-35P . The gel overlay assay showed that the anti-bacterial activity of the acid-soluble extract was relevant to two protein bands referred to as rabbit bladder protein 1 (Rab BP-1) and rabbit bladder protein 2 (Rab BP-2) . The Rab BP-1 and Rab BP-2 accounted for 2.5% and 1.2% of the total acid-soluble extract proteins, respectively . These results suggest that the long recognized ability of the normal rabbit bladder wall to kill adherent E . coli may result from the presence of endogenous antibacterial proteins associated with its mucosa.

P R Health Sci J, 1993 Dec, 12(4), 259 - 62
Endemic plants of Puerto Rico: brine shrimp lethality and antibacterial activity; Guerrero RO et al.; A total of 49 endemic plants of Puerto Rico were evaluated for their toxicological and antibacterial activities . The toxicological analysis was conducted with brine shrimp (Artemia salina Leach) lethality bioassay and the antibacterial screening was carried out by means of the agar diffusion test . In the toxicological bioassay, six plant extracts showed LC-50 values below 200 g/ml., indicating the potential presence of bioactive compounds . In the antibacterial screening, over 80% of the plant extracts displayed activity against gram positive bacteria, whereas only 6% of the extracts inhibited the growth of the gram negative bacteria.

Int Dent J, 1993 Dec, 43(6 Suppl 1), 529 - 39
The science behind caries prevention; Duckworth RM; Many agents have been shown to have an anticaries effect or to have the potential for such an effect . They can be categorised by their modes of action into three groups: those which affect plaque and plaque bacteria, those which affect tooth enamel chemistry and those which buffer oral pH . To be effective clinically, agents must not only possess intrinsic efficacy but also good oral retention characteristics . Currently, chlorhexidine is arguably the only antibacterial agent to have inhibited caries in humans, but is not employed in anticaries dentifrices and mouthrinses intended for long-term unsupervised daily use because of formulation difficulties and undesirable side effects such as tooth stain . Certain calcium salts and xylitol may also exert some clinical effect . The only extensively clinically-proven agent is fluoride . Well established reasons for the success of fluoride are its abilities to inhibit demineralisation of enamel and to enhance the remineralisation of incipient caries lesions . Recent research has highlighted the persistence of fluoride in saliva and plaque at potentially-active concentrations between successive regular applications of dentifrices and mouthrinses as a further important mechanistic step . Oral fluoride retention studies can explain recent clinical observations of increased efficacy of sodium fluoride dentifrices compared with sodium monofluorophosphate dentifrices of equivalent fluoride content.

J Dairy Sci, 1993 Dec, 76(12), 3711 - 20
Thermal behavior of bovine lactoferrin in water and its relation to bacterial interaction and antibacterial activity; Paulsson MA et al.; Heat-induced enthalpy changes in different forms of bovine lactoferrin in water were examined by differential scanning calorimetry . Two thermal transitions with varying enthalpies were observed, depending on the iron-binding status of the protein . Iron-saturated lactoferrin was more resistant to heat-induced changes than was the apolactoferrin . Native lactoferrin had two transitional peaks, and pasteurization affected only the low temperature transition . Iron-saturated lactoferrin revealed a single transitional peak that was resistant to pasteurization . However, both protein forms were completely denatured by UHT . The effect of pasteurization and UHT on the protein interaction capacity with bacteria was examined in a 125I-labeled lactoferrin binding-inhibition assay . The ability of native and iron-saturated lactoferrins to bind various bacterial species was unaffected by pasteurization . However, UHT treatment decreased this interaction capacity . Native lactoferrins, both unheated and pasteurized, showed similar antibacterial properties and moderately inhibited Escherichia coli . However, this inhibitory capacity was lost after UHT treatment . Finally, iron-saturated lactoferrin did not inhibit bacterial growth; neither pasteurization nor UHT could change this property . Thus, UHT seems to affect structural as well as certain biological properties of both native and iron-saturated bovine lactoferrins, and pasteurization seems to be a treatment of choice for products containing this protein.

Drug Saf, 1993 Dec, 9(6), 437 - 40
Photosensitivity associated with antibacterial agents; Wainwright NJ et al.; Skin reactions following the interaction of photoactive drugs and ultraviolet or visible radiation are usually rapidly reversible after drug cessation . Within the antibacterial group, photosensitivity to sulphonamides, nalidixic acid, fluoroquinolones and tetracycline members have all been reported . In general such reactions are mild, although rarely some individuals have a severe response . Precise subcellular mechanisms are drug specific, appear complex, and as yet are ill understood . Measures such as drug dosage reduction, the wearing of photoprotective clothing and use of broad spectrum sunscreens can alleviate the problem.

Antimicrob Agents Chemother, 1993 Dec, 37(12), 2633 - 7
In vitro susceptibilities of spotted fever group rickettsiae and Coxiella burnetti to clarithromycin; Maurin M et al.; The in vitro bacteriostatic activity of clarithromycin, a new macrolide derivative, against Rickettsia rickettsii, Rickettsia conorii, and "Rickettsia israeli" was determined by the plaque assay and the dye uptake assay . Both bacteriostatic and bactericidal activities of clarithromycin against the Nine Mile, Q212, Priscilla, and ME9 strains of Coxiella burnetti were evaluated by using three cell culture systems . Clarithromycin showed improved antibacterial activity compared with that of erythromycin . A bacteriostatic activity was obtained at concentrations below the reported maximum concentration of clarithromycin in human serum (about 4 micrograms/ml) for all tested rickettsiae . MICs ranged from 1 to 2 micrograms/ml for the three Rickettsia species and from 1 to 4 micrograms/ml for the C . burnetti strains . No bactericidal activity against C . burnetti was obtained when clarithromycin was used at 4 micrograms/ml.

Antibiot Khimioter, 1993 Dec, 38(12), 18 - 20
{The effect of the in-vitro interaction of antibacterial preparations on Brucella melitensis}; Samarina IV et al.; The character of drug interaction in 18 various combinations of sisomicin, amikacin, gentamicin, cefotaxime, doxycycline, trimethoprim and nitroxaline was studied by the chess board method with respect to 25 strains of Brucella melitensis . The synergistic effect with respect to the majority of the cultures was observed with the use of the combinations of gentamicin, amikacin or sisomicin with doxycycline . The combinations of the aminoglycosides with cefotaxime and sisomicin or gentamicin with rifampicin had a summation effect on the majority of the cultures . With the use of the combinations of cefotaxime with nitroxaline or trimethoprim and rifampicin with nitroxaline the effect on the majority of the cultures was indifferent . The effect was mainly antagonistic with the use of the combinations of amikacin with rifampicin, gentamicin with trimethoprim and cefotaxime with doxycycline . The effect of the combinations of gentamicin with nitroxaline and cefotaxime with rifampicin was different with respect to different strains of B . melitensis . It was indifferent, antagonistic or summation depending on the strain.

Alcohol Clin Exp Res, 1993 Dec, 17(6), 1268 - 74
Granulocyte colony-stimulating factor prevents ethanol-induced impairment in host defense in septic rats; Lang CH et al.; Ethanol is a potent immunosuppressive agent that impairs neutrophil effector function . The purpose of this study was to determine whether granulocyte colony-stimulating factor (G-CSF), a cytokine that increases neutrophil number and functional activity, could prevent the ethanol-induced impairment of antibacterial host defense . Rats were injected with human recombinant G-CSF for 2 days . Eight hr after the last injection of G-CSF, animals were infused with ethanol (or saline) for 1 hr before the subcutaneous injection of live Escherichia coli . The infusion of alcohol was continued after the bacterial challenge and produced blood alcohol levels of 275-300 mg/dl . In control animals, the injection of E . coli resulted in a marked leukopenia . There was an influx of leukocytes into the subcutaneous space where the bacteria were injected, and neutrophil accumulation in tissues adjacent to the focus of infection (i.e., dorsal skin and muscle) . Based on myeloperoxidase activity, there was no detectable accumulation of neutrophils in other soft tissues . In acutely intoxicated rats, leukocyte migration to the inflammatory site was impaired, and the number of viable bacteria isolated from the subcutaneous pocket was markedly increased . G-CSF prevented the sepsis-induced leukopenia, increased the influx of neutrophils in to the infection site, reduced the number of bacteria in the subcutaneous lavage fluid, and decreased the incidence of bacteremia in ethanol-treated rats when compared with rats not receiving G-CSF . These results demonstrate that G-CSF is a potent immunomodulator that stimulates neutrophil recruitment selectively to the site of infection and that can be used to ameliorate the ethanol-induced impairment in bacterial host defense.

Antimicrob Agents Chemother, 1993 Dec, 37(12), 2684 - 7
Immunosuppressive activity of fosfomycin on human T-lymphocyte function in vitro; Morikawa K et al.; Recent investigations have shown that some antibiotics also work as immunomodulators . We have recently reported that fosfomycin (FOM) has an immunomodulatory effect on human B-cell activation . FOM is a unique antibiotic which is chemically unrelated to any other known antibacterial agent . In the present study, we examined the effect of FOM on human T-cell function . FOM inhibited the proliferation of human lymphocytes induced by polyclonal T-cell mitogens in a dose-dependent manner . FOM also strongly suppressed mixed lymphocyte reaction and interleukin-2 (IL-2) production by T cells . Moreover, FOM inhibited the expressions of IL-2 receptor (CD25) and transferrin receptor (CD71) on the activated T-cell surfaces . These data suggest that FOM may block the T-cell division during the transition from G1 to S phase of the cell cycle . Combined treatment with FOM and low-dose cyclosporin A or FK506 caused additive or synergistic suppression of T-cell proliferation, but not on IL-2 receptor expression . It seems that the mode of action of FOM on T-cell function involves a specific suppression of IL-2 production.

Age Ageing, 1993 Nov, 22(6), 450 - 6
Toxic epidermal necrolysis (Lyell syndrome) in 77 elderly patients; Bastuji-Garin S et al.; Toxic epidermal necrolysis is a rare, severe drug-induced disorder characterized by extensive epidermal loss . This study used the data of a national survey looking for all cases which occurred during a five-year period . The incidence of toxic epidermal necrolysis (cases/million/year) was 2.7 times higher among elderly than among younger adults . In the elderly population no female preponderance was found but clinical patterns were similar . The fatality of toxic epidermal necrolysis was twice as high in the elderly patients (51%) as in the younger (25%) . The drugs incriminated in most cases of toxic epidermal necrolysis were the same in both groups (NSAIDs, antibacterials and anticonvulsants).

Antimicrob Agents Chemother, 1993 Nov, 37(11), 2261 - 4
Azithromycin inhibition of intracellular Legionella micdadei; Donowitz GR et al.; Legionella micdadei is an intracellular parasite that is ingested, but not killed, by leukocytes . Within monocytes, the organism has been shown to grow 1.0 to 2.0 log10 units over 48 h (D . L . Weinbaum, R . R . Benner, J . N . Dowling, A . Alpern, A . W . Pasculle, and G . R . Donowitz, Infect . Immun . 46:68-73, 1984) . Intracellular L . micdadei would appear to be a useful model in which to study the effect of antibiotics which accumulate intracellularly . Azithromycin, a newly introduced azalide, is highly concentrated within leukocytes and was therefore studied to determine its effect on a single strain of L . micdadei that had been ingested by human monocytes . Peripheral blood monocytes were allowed to ingest L . micdadei and extracellular, nonadherent organisms were subsequently removed by washing . Cells and cell-associated bacteria were then incubated at 0, 24, and 48 h in media with serial concentrations of azithromycin at sub-MIC levels (less than 1.0 microgram/ml) . L . micdadei in cells not exposed to azithromycin grew 0.8 +/- 0.1 log10 units (mean +/- standard deviation) at 24 h and 1.7 +/- 0.4 log10 units at 48 h . At both 24 and 48 h, the lowest concentrations of azithromycin tested (0.02 microgram/ml) significantly inhibited bacterial growth in monocytes (P = 0.02) . A stepwise inhibition of L . micdadei CFUs was noted with increasing azithromycin concentrations . In contrast, when cells were exposed to antibiotic before ingesting L . micdadei, a less effective antibacterial effect was noted . Under certain in vitro conditions, azithromycin is a potent agent against intracellular L . micdadei.

J Antibiot (Tokyo), 1993 Nov, 46(11), 1731 - 9
Synthesis and biological activity of derivatives of glycopeptide antibiotics eremomycin and vancomycin nitrosated, acylated or carbamoylated at the N-terminal; Pavlov AY et al.; Nitrosation, carbamoylation or acylation of the glycopeptide antibiotics eremomycin or vancomycin produced series of derivatives substituted at the N-terminus of the peptides . Though the modified amino group in these derivatives is not capable of protonation, N-nitroso derivatives retain antibacterial activity in vitro and in vivo . N-Carbamoyleremomycin has low activity, and N-Cbz-eremomycin and N-Boc-eremomycin are devoid of antibacterial activity, both in vitro and in vivo.

Chemotherapy, 1993 Nov-Dec, 39(6), 386 - 9
Anti-Brucella activity of Ro 23-9424, a dual-action antibacterial; Qadri SM et al.; The in vitro activity of dual-acting antibacterial Ro 23-9424 was determined by the agar dilution method against 126 clinical isolates of Brucella melitensis . It was compared with fleroxacin, ciprofloxacin and five conventional drugs . MIC50 and MIC90 for Ro 23-9424 were 1.0 and 4.0 mg/l, respectively, as compared with 0.25 and 0.5 mg/l for fleroxacin and ciprofloxacin . One strain which was resistant to other fluoroquinolones, with an MIC of > 8.0 mg/l, did not show cross-resistance to Ro 23-9424 and had an MIC of 4.0 mg/l . All the strains were susceptible to conventional drugs like gentamicin, streptomycin rifampicin, tetracycline and trimethoprim-sulfamethoxazole, with MICs ranging between 0.12 and 2.0 mg/l . Ro 23-9424 did not exhibit in vitro synergy with any of the conventional drugs.

Chromosome Res, 1993 Nov, 1(4), 253 - 5
Chromosomal localization of the lysozyme gene cluster in river buffalo (Bubalus bubalis L.); Iannuzzi L et al.; Lysozyme (LYZ) is an antibacterial enzyme which allows the digestion of bacteria present in tears and saliva . In the true stomach of ruminants LYZ breaks open the bacteria of the foregut, which are subsequently digested by typical mammalian digestive enzymes, allowing the incorporation of nutrients from the bacteria . Southern analysis with a single exon from a cow lysozyme gene revealed that there are about 10 genes in ruminants (Irwin & Wilson 1989), while pig and primates have a single lysozyme gene (Swanson et al . 1991) and camels have two (Irwin et al . 1992) . The higher number of LYZ genes in ruminants is believed to be the result of gene duplication associated with the evolution of foregut fermentation (Irwin et al . 1992) . Recently, the genomic organization of the lysozyme gene family has been determined in domestic cattle, and, using a cocktail of genomic clones, the lysozyme gene cluster (LYZ/) was assigned to chromosome (Chr) 5, band 23 by fluorescence in situ hybridization (FISH) (Gallagher et al . 1993) . In our continued effort to test the genetic homology of conserved chromosome banding regions between cattle and river buffalo, and to extend the river buffalo physical gene map, we have mapped the LYZ/ by FISH and R-banding.

Acta Pharm Hung, 1993 Nov, 63(6), 319 - 26
Evaluation of the effect of formulation type of povidone/iodine preparations on infection and wound healing; el-Sayed AM et al.; Different povidone/iodine (PI) dosage forms (e.g . solution, ointment, gel) in various PI concentrations and percentage of water were prepared . The efficacy of these formulations was assessed in vitro bacteriologically and clinically in large number of human and animal subjects . Comparison of their effect with those of other agents in some cases was made . The results obtained indicated that the antibacterial activity of PI in different formulation types was in the order: aqueous solution > water soluble ointment base containing 20% (w/w) water > aqueous gel base > water soluble ointment base containing 10% (w/w) water > water soluble ointment base > oleaginous base . PI is more efficient when comparing it with some conventional antiseptics, used clinically, and enhances wound healing process.

Pharmacol Ther, 1993 Nov, 60(2), 367 - 80
Cyclothialidine and its congeners: a new class of DNA gyrase inhibitors; Goetschi E et al.; Cyclothialidine is a new, potent DNA gyrase inhibitor isolated from Streptomyces filipinensis . However, it exhibits hardly any growth-inhibitory activity against intact bacterial cells . To explore its potential with regard to the development of a new type of antibacterial, a flexible synthetic route was worked out (i) to investigate the structural requirements for DNA gyrase inhibition and (ii) to search for congeners exerting antibacterial activity . The structure of cyclothialidine was confirmed by total synthesis . Marked DNA gyrase inhibitory activity was found for a number of analogs, a common feature of them being the bicyclic 12-membered lactone bearing one phenolic hydroxy group . Congeners of cyclothialidine were found to exhibit a moderate, but broad-spectrum, in vitro activity against Gram-positive bacteria . Therefore, the DNA gyrase inhibitory principle contained in cyclothialidine can be considered as the basis for a new class of antibacterial agents.

Phytochemistry, 1993 Nov, 34(5), 1241 - 3
Structure-activity relationships of synthetic tigogenyl glycosides; Takechi M et al.; Haemolytic activities of the five tigogenyl diglycosides and a maltotrioside were much stronger than those of nine monoglycosides . Among these glycosides, the glucoside, galactoside, maltoside, lactoside, gentiobioside, melibioside and maltotrioside had strong antifungal activity . By contrast, none of these glycosides showed any antibacterial activity.

J Immunol, 1993 Nov 1, 151(9), 5011 - 21
Human antilipid A monoclonal antibodies bind to human B cells and the i antigen on cord red blood cells; Bhat NM et al.; We describe two independently derived human mAb, A6(H4C5) and 216, initially selected for their reactivity to the lipid A domain of bacterial LPS, which also react with the following Ag: the i Ag present on cord RBC, a ligand on human B lymphocytes, and to certain autoantigens, defining these mAb as polyreactive . Both mAb have specific affinity for a carbohydrate epitope consisting minimally of a disaccharide with an acyl substitution at the 2-carbon position . Structural examination of the diverse Ag recognized by the two antibodies reveals the presence of this carbohydrate structure required for antibody binding . A6(H4C5) and 216 are IgM in isotype, but differ in their L chain expression . Molecular analysis shows that both the mAb are encoded by a highly conserved VH4 gene, designated VH4-21 . This gene encodes a number of autoantibodies, particularly cold agglutinins . Specific recognition of lipid A and of a carbohydrate epitope on B lymphocytes by the two human mAb suggests a dual function for the highly conserved VH4-21 gene in antibacterial response and in B cell development and regulation.

J Chromatogr, 1993 Oct 29, 620(2), 211 - 6
Determination of a new antibacterial agent (Ro 23-9424) by multidimensional high-performance liquid chromatography with ultraviolet detection and direct plasma injection; Szuna AJ et al.; Analysis of a new antibacterial agent, Ro 23-9424 (I), in plasma has been complicated by the fact that its metabolite, fleroxacin (II), is formed not only in vivo, but also nonenzymatically by the hydrolysis of the ester bond of I . In order to minimize sample preparation time and possible hydrolysis during sample preparation, a high-performance liquid chromatographic procedure was developed which features direct injection of plasma and multidimensional chromatography . The first dimension size-exclusion separation allows plasma proteins to elute with the column void volume . The second dimension reversed-phase column provides a high-resolution separation dependent upon the hydrophobicity of the sample species . With a 5-microliters injection, the limit of quantitation of the method is 0.35 microgram/ml for I and 0.27 microgram/ml for II . The method was used to determine steady state plasma vs . time profiles for I and II from 750 mg i.v . doses of I administered twice daily.

J Med Chem, 1993 Oct 29, 36(22), 3444 - 8
Fluorocyclopropyl quinolones . 1 . Synthesis and structure-activity relationships of 1-(2-fluorocyclopropyl)-3-pyridonecarboxylic acid antibacterial agents; Atarashi S et al.; A series of 1-(2-fluorocyclopropyl)-3-pyridonecarboxylic acids has been prepared . These derivatives are characterized by having a fluorine atom at the 2-position on the cyclopropane ring as the N1 substituent and consist of both cis and trans stereoisomers . Structure-activity relationship studies indicate that the cis derivatives are more potent against Gram-positive bacteria than the corresponding trans counterparts, but the difference in potency against most Gram-negative bacteria is much smaller . The inhibitory effect of compounds 4, 5, 26, 27, 38, and 39 on supercoiling activity of DNA gyrase obtained from E . coli KL-16 correlated with their MICs against the same strain and also depend on their (26, 27, 38, 39) stereochemistry . Introduction of a fluorine atom on the cyclopropyl group resulted in the reduction of lipophilicity compared with the corresponding nonfluorinated quinolones.

J Med Chem, 1993 Oct 29, 36(22), 3224 - 9
Structure-activity relationship within a series of pyrazolidinone antibacterial agents . 2 . Effect of side-chain modification on in vitro activity and pharmacokinetic parameters; Ternansky RJ et al.; The structure-activity relationship among a series of novel pyrazolidinone antibacterial agents is described . Specifically, the effect of modification of the side chain attached to the nitrogen at C-7 was explored in an attempt to improve the potency and spectrum of activity . This approach was successful in identifying several compounds having good in vitro profiles . These top candidates were then evaluated for their activity in vivo, and their pharmacokinetic behavior in various animal models was explored . This information proved critical for the identification of candidates for clinical evaluation.

J Med Chem, 1993 Oct 29, 36(22), 3219 - 23
Structure-activity relationship within a series of pyrazolidinone antibacterial agents . 1 . Effect of nuclear modification on in vitro activity; Ternansky RJ et al.; The synthesis and biological evaluation of a series of pyrazolidinone-containing mono- and bicyclic compounds are described . The results of this investigation indicate that the {3.3.0} ring system bearing strongly electron-withdrawing groups in the 3-position provides the optimal arrangement for antibacterial activity . Two highly potent derivatives, LY193239 and LY255262, have been selected for further preclinical evaluation.

J Biol Chem, 1993 Oct 25, 268(30), 22672 - 9
Artificial duplication of the R67 dihydrofolate reductase gene to create protein asymmetry . Effects on protein activity and folding; Zhuang P et al.; R67 dihydrofolate reductase (DHFR), encoded by an R plasmid, provides resistance to the antibacterial drug trimethoprim . This enzyme does not exhibit any structural or sequence homologies with chromosomal DHFR . A recent crystal structure of tetrameric R67 DHFR (D . Matthews, X . Nguyen-huu, and N . Narayana, personal communication) shows a single pore traversing the length of the molecule . Numerous physical and kinetic experiments suggest the pore is the active site . Since the center of the pore possesses exact 222 symmetry, mutagenesis of residues designed to explore substrate binding will probably also affect cofactor binding . As a first step in breaking this inevitable symmetry in R67 DHFR, the gene has been duplicated . The protein product, R67 DHFRdouble, is twice the molecular mass of native R67 DHFR and is fully active with kcat = 1.2 s-1, Km(NADPH) = 2.7 microM and Km(dihydrofolate) = 6.3 microM . Equilibrium unfolding studies in guanidine-HCl indicate R67 DHFRdouble is more stable than native R67 DHFR at physically reasonable protein concentrations . Microcalorimetry studies show native R67 DHFR undergoes fully reversible thermal unfolding . Unfolding can be described by a two-state process since a ratio of delta Hcalorimetric to delta Hvan't Hoff equals 0.96 . In contrast, thermal unfolding of R67 DHFRdouble is not fully reversible and possesses an oligomerization component introduced by the gene duplication event.

Carbohydr Res, 1993 Oct 18, 249(1), 57 - 76
Study on fluorination-toxicity relationships . Syntheses of 1-N-{(2R,3R)- and (2R,3S)-4-amino-3-fluoro-2-hydroxybutanoyl} derivatives of kanamycins; Takahashi Y et al.; (2R,3R)- And (2R,3S)-4-azido-3-fluoro-2-hydroxybutanoic acids (11 and 22) have been prepared from 3-deoxy-3-fluoro-1,2-O-isopropylidene-alpha-D-glucofuranose (1) and 3,5-di-O-benzyl-1,2-O-isopropylidene-alpha-D-xylofuranose (12), respectively . They were then coupled to the N2N-1 group of suitably protected kanamycin A or kanamycin B analogs to give, 1-N-{(2R,3R)- and (2R,3S)-4-amino-3-fluoro-2-hydroxybutanoyl}kanamycins (32-35) . This group of compounds (32-34) exhibited similar antibacterial activity and toxicity level as those of the corresponding 1-N-{(S)-4-amino-2-hydroxybutanoyl} (AHB) derivatives of kanamycins . The base strength of the H2N-4"' group of 32 and 34, as determined by 13C NMR spectroscopy (in D2O) at varying pD values, was found to be lower when compared to the basicity for the corresponding AHB analogs . The relationship between observed toxicity and base strength of the H2N-4"' group is discussed.

Eur J Biochem, 1993 Oct 15, 217(2), 639 - 44
Solution conformation of an antibacterial peptide, sarcotoxin IA, as determined by 1H-NMR; Iwai H et al.; The solution conformation of sarcotoxin IA, which is an antibacterial peptide isolated from Sarcophaga peregrina with a molecular mass of 4 kDa, was determined by NMR spectroscopy and hybrid distance geometry/dynamical simulated annealing calculations . On the basis of 227 experimental constraints, including 185 distance constraints obtained from NOE and 42 constraints associated with 21 hydrogen bonds, a total of 18 converged structures of sarcotoxin IA were obtained . The final 18 converged structures exhibit backbone-atomic root-mean-square differences about the averaged coordinate positions of 0.070 +/- 0.027 nm for residues 3-23 and 0.040 +/- 0.017 nm for residues 28-38 . It has been indicated that sarcotoxin IA consists of two amphiphilic alpha-helical regions, i.e . helix I (Leu3-Gln23) and helix II (Ala28-Ala38), with a hinge region (Gly24-Ile27), which connects helix I and helix II . We conclude that these two amphiphilic helical segments of sarcotoxin IA are of importance for the expression of the antibacterial activity.

Tissue Cell, 1993 Oct, 25(5), 791 - 7
Immunohistochemical localization of lactoferrin in bovine exocrine glands; Inoue M et al.; The localization of lactoferrin (LF) was studied in bovine exocrine glands by the peroxidase-antiperoxidase method . In general, LF immunoreactivity was demonstrated in most of the serous demilunes of the mixed glands and in some but not all acinar cells of the serous glands . LF was not detected in the acinar cells of the mucous glands . LF immunoreactive cells were seen in the nasal and tracheal glands . The lacrimal and mammary glands were stained intensely, while the sweat glands were not stained . In the major and minor salivary glands, LF immunoreactivity was demonstrated in the serous demilunes and acini of the mixed glands and in some serous cells of the pure serous parotid gland . LF immunoreactivity was not seen in the gastrointestinal tract and pancreas, but the serous gland in the lamina propria of the bile duct was stained positively . In the male reproductive tracts, the prostate and bulbourethral glands were stained positively, but the vesicular gland was negative . In the female reproductive system, the uterine and Bartholin glands, the epithelial cells of the cervix and ampulla of the uterine tube reacted positively . However, the lesser vestibular gland did not react for LF . The present findings, that LF was demonstrated in the exocrine glands located mainly in the gateways of the digestive, respiratory and reproductive systems, may morphologically support the antibacterial role of LF.

Pharmazie, 1993 Oct, 48(10), 738 - 40
Vermiculin derivatives . Part 1: Synthesis of vermiculin derivatives; Proksa B et al.; Hydrogenation of the macrodiolide antibiotic vermiculin (1) over Adams catalyst afforded {8S, 16S}-8,16-bis(2'-oxopropyl)-1,9- dioxyacyclohexadeca-2,5,10,13-tetrone (2), {8S, 16S}-8,16-bis(2'-oxopropyl)-13-hydroxy-1,9-dioxacyclohexadeca- 2,5,10-trione (3), {8S,16S}-8,16-bis(2' oxopropyl)-1,9- dioxacyclohexadeca-2,5,10-trione (4) together with {7S}-4,9-dioxo-7-(4',9'-dioxodecanoyloxy)decanoic acid (5) . Hydrogenation of diolide 1 over Pd/C gave tetrahydrovermiculin (2) only . The prepared compounds showed lower antibacterial and cytotoxic activities than vermiculin (1).

New Microbiol, 1993 Oct, 16(4), 309 - 14
Production and release of tumor necrosis factor alfa, interleukin-1B and interleukin-6 by human mononuclear leukocytes stimulated with pertussis toxin; Torre D et al.; Pertussis toxin (PT) has been previously shown to affect a wide variety of immune responses and to cause lymphocyte proliferation . In this study, we examined the effect of PT on cultured human peripheral blood lymphocytes and monocytes with the regard to the capability of this toxin to stimulate the production and release of various cytokines . PT was found to induce the production and release of Tumor Necrosis Factor alfa (TNF-alfa) and Interleukin-6 (IL-6) by both human lymphocytes and monocytes and IL-1 (IL-1B) beta by human monocytes in culture . Most activities of PT in vitro were achieved at the optimal concentration range of 1-0.01 microgram/ml, which is responsible for the adjuvant effect of PT in vivo . Since TNF-alfa, IL-1 beta and IL-6 are potent mediators of inflammation, the production and release of these cytokines by PT and Bordetella pertussis itself may play an important role in antibacterial defenses against such infection.

Antimicrob Agents Chemother, 1993 Oct, 37(10), 2217 - 23
Reduced phototoxicity of a fluoroquinolone antibacterial agent with a methoxy group at the 8 position in mice irradiated with long-wavelength UV light; Marutani K et al.; A newly developed fluoroquinoline, Q-35 (8-OCH3), in which a methoxy group was substituted at the 8 position of the quinoline nucleus, was very stable under irradiation with long-wave UV light (UVA) . Derivatives, a fluoroquinolone with no substitution (the 8-H analog) and one in which a fluorine was substituted (the 8-F analog), were degraded in their solutions by the UVA irradiation . The phototoxic inducibility by these derivatives was further studied in a murine model . When mice were dosed orally with 800 mg of Q-35 (8-OCH3) per kg of body weight, the maximum dose given, and exposed to the UVA light, no inflammatory lesions were observed in their ears . Ear redness was marked in mice given more than 12.5 mg of the 8-F analog or 200 mg of the 8-H analog per kg . Histopathological changes, edema, and infiltration of neutrophils were also observed microscopically in groups receiving the 8-H or 8-F analog but not in groups receiving Q-35 (8-OCH3) . Similar inflammatory reactions were observed to occur in a dose-dependent manner with other available fluoroquinolone antibacterial agents such as lomefloxacin, enoxacin, norfloxacin, ciprofloxacin and ofloxacin . These results suggest that the introduction of a methoxy group at the 8 position of the quinolone nucleus is important for the reduction of phototoxicity.

Z Gastroenterol, 1993 Oct, 31(10), 587 - 91
{Pancreas penetration by ofloxacin--a pilot study}; Koch K et al.; The use of antibiotics in patients with necrotizing pancreatitis is indicated since bacterial complications are the most common cause of death in this condition . Olfloxacin was studied in six patients regarding its permeation into pancreatic juice and bile and into pancreatic tissue in cases of chronic pancreatitis and pancreatic carcinoma . The peak concentrations in pancreatic juice (3.7 mg/l) and bile (12.9 mg/l) were found 20 minutes after i.v . administration of 3 mg/kg ofloxacin, these are 79 and 275% of the corresponding serum level, respectively . Pancreatic tissue concentrations varied between 54 and 333% of serum values in relation to the removal time of specimens and to the stage of inflammation . After three days and five days of ofloxacin treatment with doses of 2 x 200 mg daily even in pancreatic necroses concentrations were detected between 0.8 and 3.7 mg/kg wet weight . This suggests that in all pancreatic compartments analyzed, sufficient antibacterial ofloxacin levels above the MIC of relevant germs were found . Therefore, from a pharmacokinetic point of view, ofloxacin could be a potentially effective drug in prophylaxis and therapy of bacterial infections of the pancreas.

Cesk Farm, 1993 Oct, 42(5), 218 - 22
{Biological effects of substances similar to salicylanilides . 3-aryl-2H, 4H-benz(e)(1,3)oxazine-2, 4-diones and thiosalicylanilides}; Waisser K et al.; The review paper is the first collected communication about the biological activity of 3-aryl-2H,4H-benz(e)(1,3)oxazine-2,4-diones and thiosalicylanilides . The substances of the above mentioned structures show a number of biological activities (antibacterial, antituberculous, antimycotic, anthelmintic, molluscocidal, neuroleptic, analgesic and anti-inflammatory) which can be modelled by structural changes . Only very few of them have been hitherto introduced into practice as anthelmintic agents, or agents with a special purpose (destroying the sea lamprey in Canadian lakes) . In the group of 3-aryl-2H,3H-benz(e)(1,3)-oxazine-2,4-diones, i.e . substances developed from salicylanilides by the action of alkyl-chloroformiates, antibacterial activity is reported in refs . 3-12, antituberculous activity in refs . 13, 14, antimycotic activity in refs . 5, 6, 9, 12, 15, 16, anthelmintic activity in refs . 6,917-20, molluscocidal activity in refs . 6, 21, analgesic and anti-inflammatory activity in refs . 22-24, herbicidal activity in refs . 25, 26, allergenic activity in ref . 27 . In the group of salicylanilides, antibacterial activity is reported in refs . 28-37, antimycotic activity in refs . 28-36, antiprotozoal activity in ref . 35, anthelmintic activity in refs . 28-40, 49, molluscocidal activity in refs . 7, 28-36 . The present paper furthermore sums up the papers concerned with the toxicities of the above-mentioned agents . Though the peak of research of the groups of the above-mentioned structure was in the 1960s and 1970s, papers investigating their biological activity can be encountered also at present.

Hematol Oncol Clin North Am, 1993 Oct, 7(5), 961 - 1002
Special considerations for the patient undergoing allogeneic or autologous bone marrow transplantation; Hiemenz JW et al.; Improvements in the diagnosis, treatment, and prevention of infectious complications of bone marrow transplantation over the past two decades have markedly reduced the morbidity and mortality of this procedure . We are now able to begin early empiric antibiotic coverage with less toxic, but equally effective, antibacterial agents . Once believed to be uniformly fatal, complications such as CMV pneumonia are now considered treatable in at least half the cases with a combination of intravenous immunoglobulin and ganciclovir . Although probably the most controversial, prophylactic therapy has improved the outcome of patients undergoing bone marrow transplantation . The appropriate setting, agents to use, dose, and dose intervals will require further study in coming years . In the introduction to this article, we attempted to outline what is known about the immunobiology of bone marrow transplantation . A clear understanding of this process helps us recognize and anticipate the infectious complications encountered in this population of patients . It may also allow clinicians to focus more on immune augmentation as a means of prevention, as has been attempted with the newly available cytokines and the use of intravenous immunoglobulin infusions . Despite improvements in diagnosis, treatment, and prevention, infectious complications remain the leading cause of morbidity and mortality in the patient undergoing bone marrow transplantation . Future studies are required in this area to build on the successes of the last two decades.

Biol Mass Spectrom, 1993 Oct, 22(10), 595 - 9
Confirmation of danofloxacin residues in chicken and cattle liver by microbore high-performance liquid chromatography electrospray ionization tandem mass spectrometry; Schneider RP et al.; A specific assay is described for the confirmatory identification of danofloxacin residues in edible tissues of cattle and chicken . The assay utilizes on-line microbore high-performance liquid chromatography and pneumatically assisted electrospray tandem mass spectrometry (MS/MS) . Collision-induced dissociation of the danofloxacin protonated molecule results in two significant daughter ions . Monitoring both ions provides the specificity required for this confirmatory assay . Optimum electrospray and MS/MS operating conditions permitted the specific monitoring of danofloxacin and the confirmation of its residues in chicken and cattle liver extracts down to 50 ppb . The analysis of control liver or the commercially available antibacterial quinolones enrofloxacin and its metabolite ciprofloxacin gave no response under the assay conditions . The ratios of the two daughter ions were similar for danofloxacin standard solutions, fortified tissues and incurred tissues.

Semin Oncol, 1993 Oct, 20(5 Suppl 6), 102 - 9
The platelet-refractory bone marrow transplant patient: prophylaxis and treatment of bleeding; Benson K et al.; Refractoriness to platelet transfusions remains a significant problem for oncology patients, occurring in 30% to 70% of multiply transfused recipients with bone marrow failure . Nonimmune causes are often present and include disseminated intravascular coagulation, concurrent use of amphotericin B, infection, presence of palpable spleen, use of antibacterial antibiotics, bleeding, veno-occlusive disease, and fever . Immune causes are also commonly responsible for refractoriness, with HLA alloimmunization dominating the list of immune factors . HLA antibodies can be identified in 25% to 30% of transfused leukemia patients and can be present in as many as 80% of aplastic anemia patients . Developing a consistent approach to managing these refractory patients is essential to preventing and treating bleeding manifestations . An HLA type should be obtained for all patients anticipated to have chronic transfusion requirements . Screening for lymphocytotoxic antibodies can confirm suspected HLA alloimmunization . Histocompatible platelets (cross-match compatible and HLA matched) should be provided for all patients with HLA antibodies . A number of other therapeutic modalities have been used in an effort to manage the alloimmunized patient; most of these methods have had little or no proven benefit . When bleeding develops in the alloimmunized patient, there are few therapeutic choices . If histocompatible platelets are unavailable or unsuccessful, massive platelet transfusions of pooled platelet concentrates are commonly used, although this practice is of no proven benefit . While antifibrinolytic agents have been available for over 30 years, they are only recently being applied to control bleeding in chronic thrombocytopenia . We have successfully managed bleeding episodes in thrombocytopenic bone marrow transplant recipients with the use of epsilon aminocaproic acid . A number of these patients were platelet refractory with demonstrable platelet antibodies . Platelet refractoriness continues to plague multiply transfused oncology patients . While preventative measures may ultimately benefit some patients, this problem will continue to manifest itself . A consistent approach to transfusion support needs to be implemented to best manage this challenging patient population.

Int Dent J, 1993 Oct, 43(5), 499 - 505
Contemporary use of agents in the control of progressive periodontitis; Gjermo P; Mechanical treatment of periodontitis is effective in most cases . However, there are cases which respond poorly and in which chemotherapy may be appropriate . Topical antibacterials applied supragingivally have limited or no effect upon established periodontitis caused by subgingival plaque . Subgingival application of antibacterial agents have in some studies shown a certain effect upon the inflammatory response particularly when applied in addition to conventional mechanical treatment . Long term results are not convincing . Speculation that some forms of periodontitis may be regarded as specific infections have led to the use of antibiotics in the treatment of such conditions . The drugs most often recommended are tetracyclines and imidazoles, and there are reports indicating arrest or retardation of further disease progression when they are applied as an adjunct to conventional mechanical treatment . Recently, local application of antibiotics in slow release devices has been claimed to be effective in combating periodontitis . Data presented so far have mostly shown reduced inflammation, while the effect upon the progression of the disease remains largely unknown . There seems to be general agreement that use of antibiotics in some cases of periodontitis is advantageous, but only if it is used as an adjunct to scaling and root planing.

Stomatologiia (Mosk), 1993 Oct-Dec, 72(4), 61 - 4
{The results of comprehensive caries prophylaxis in children under endemic goiter conditions}; Pashaev ChA et al.; Caries prevention was carried out in 800 children aged under 7 living in regions endemic for goiter . The complex of preventive measures included natrium fluoratum tablets (Polfa, Poland), a combination of fluoride lacquer with 3% remodent, Azerbaijan black tea tincture with F, 10 mg/l, all of these combined with antistrumin, an iodine-containing drug . Clinical data, enamel acid solubility values, data of microbiologic examinations of dental deposit, status of natural antibacterial defense of tissues and organs of the oral cavity demonstrated a high caries-preventive efficacy of the measures taken . A high caries-preventing efficacy of tea preparations has been revealed, their antibacterial properties among other things.

Stomatologiia (Mosk), 1993 Oct-Dec, 72(4), 12 - 5
{The treatment of inflammatory periodontal diseases using prolonged-action pentoxyl}; Chuchmai GS et al.; Periodontal immunomorphology was found changed during an inflammation, these changes presenting as fixation of immune complexes with IgA and IgG in the periodontal tissues . The intensity of the immunopathologic reaction corresponded to the severity of periodontal inflammation, correlated with clinical evaluation of periodontal status and capillary stability level reduced under the effect of treatment, and was effectively arrested by pentoxil directly in the periodontal focus of inflammation . Due to its immunoregulating effect on periodontal tissues and antibacterial action pentoxil application as a component of carbohydrate gel prolonging its action helped attain favorable and stable results in periodontitis treatment.

Antibiot Khimioter, 1993 Oct-Nov, 38(10-11), 26 - 34
{Antibiotic pharmacokinetic indices and their significance in working out antibacterial therapy regimens and predicting their efficacy}; Navashin SM et al.; The data on the value of pharmacokinetic parameters and pharmacologic properties of antibiotics for the development of optimal regimens of antibacterial therapy are presented . The impact of various symptoms and syndromes of purulent septic processes (uremia, anemia, obesity or hyperbilirubinemia) on antibiotic pharmacokinetics is discussed . Approaches to the improvement of schemes for antibiotic therapy of various pathological conditions are noted . Procedures (a microbiological one and those with the use of apparatus) for the determination of antibiotic concentrations in serum and tissues are described . Factors useful for the development of individual regimens of antibiotic therapy of various nosologic forms of infectious inflammatory diseases are indicated: some indices characterizing susceptibility of the pathogen to the drug used (minimum antibacterial, minimum inhibitory and bactericidal concentrations), difficulties with their interpretation (the phenomena of the pathogen persistence, microbial tolerance and Eagle's effect), environmental influences in the infection foci on the drug concentration.

C R Acad Sci III, 1993 Oct, 316(10), 1218 - 24
Expression and nuclear translocation of the rel/NF-kappa B-related morphogen dorsal during the immune response of Drosophila; Reichhart JM et al.; The rel/NF-kappa B-related morphogen dorsal is a maternally expressed gene which is involved in the control of the dorso-ventral axis during early embryogenesis of Drosophila . We show that this gene is also expressed in the fat body of larvae and adults of Drosophila as well as in a tumorous blood cell line: its expression is noticeably enhanced upon bacterial (or lipopolysaccharide) challenge . This challenge also induces within 15-30 min a nuclear translocation of the dorsal protein . The genes encoding inducible antibacterial peptides in Drosophila contain kappa B-related nucleotide sequences and we show that the dorsal protein can bind to such motifs and sequence-specifically transactivate a reporter gene in co-transfection experiments with a Drosophila cell line . However, in dl1 mutants, in the absence of dorsal protein, the genes encoding antibacterial peptides retain their inducibility, suggesting a multifactorial control . The results indicate that in addition to its role in embryogenesis, dorsal is involved in the immune response of Drosophila . They also strengthen the analogy between the mammalian acute phase response and the insect immune response.

Lik Sprava, 1993 Oct-Dec, (10-12), 79 - 81
{The immunological aspects of the antibacterial therapy of peptic ulcer patients}; Bychkova NG et al.; Essence and potency of immunological effects produced by some anti-bacterial drugs used in the treatment of peptic ulcer were determined in the course of immunological survey of patients . Trichopol and--to the less extent--furazolidone were established to provide immunocorrective effect and prevent exacerbation better than amoxicillin . The latter, to the contrary, aggravates secondary immune deficiency.

Lik Sprava, 1993 Oct-Dec, (10-12), 45 - 7
{The effect of different types of immunocorrective therapy on the clinical course of chronic myeloleukemia}; Guseva SA; Influence of various patterns of immunocorrective therapy on clinical course of chronic myeloleukemia (CML) was studied . It was shown that combinations of drugs with different pharmacological effects provide more than 5-fold decrease in incidence of infection-related complications and promote rapid recovery from infections during antibacterial treatment.

Biochem Biophys Res Commun, 1993 Sep 15, 195(2), 1077 - 80
The oxazolidinone antibacterial agent DuP 105 does not act on cell wall biosynthesis or on a beta-lactamase; Silverman RB et al.; (S)-3-(4-Methylsulfinylphenyl)-5-(acetamidomethyl)oxazolidinone (DuP 105; 1, R = CH3SO, R' = Ac), one of a new class of antibacterial agents, is shown to be devoid of inactivation and inhibitory properties toward bacterial cell wall biosynthesis and toward a beta-lactamase . This is consistent with the idea that this class of compounds acts by a route different from that of the beta-lactam antibiotics.

Ugeskr Laeger, 1993 Sep 13, 155(37), 2861 - 6
{Translocation and multiple organ failure}; Jensen TH et al.; A review of bacterial translocation and multiple organ failure (MOF) is presented . Splanchnic ischaemia plays a central role in the development of MOF, but the exact mechanism of translocation is unclear . The concentration of endotoxins and bacteria in the gut is high . The critically ill patient is often treated with antibiotics with a broad antibacterial spectrum and overgrowth of Gram negative bacteria will take place in the gut favouring the translocation phenomenon . The regime of selective gut decontamination is discussed . Regional and systemic oxygen kinetics together with metabolic markers are important in detecting splanchnic ischaemia . Hepatic vein catheterisation and gastric mucosa pHi are discussed . The regional inflammation in the gut is often initiated by endotoxins, which stimulate the cytokines IL-1, IL-6 and TNF . Another important factor that can accentuate inflammation of the gut is reperfusion injury . A proposal for treatment of splanchnic ischaemia and translocation is discussed i.e.: optimizing central haemodynamic parameters, optimizing the regional microcirculation, treatment with antibodies to endotoxins, gut decontamination and early enteral nutrition . When splanchnic hypoperfusion is detected it cannot be ignored . It may be possible to correct the hypoperfusion with early gastrointestinal resuscitation and to thereby reduce the duration and mortality of MOF . The above mentioned suggestions are all very demanding of resources, but have to be considered in gut directed therapy.

J Med Chem, 1993 Sep 3, 36(18), 2621 - 6
Synthesis and antibacterial activity of a new series of tetracyclic pyridone carboxylic acids; Jinbo Y et al.; A series of novel tetracyclic pyridone carboxylic acids replacing the 10-position oxygen atom of 9,1-(epoxymethano)-7-fluoro-8-(4-methyl-1-piperazinyl)-5-oxo-5H-thiazolo {3,2-alpha}quinoline-4-carboxylic acid by imino groups (NR; R = Me, Et, c-Pr, allyl, Ph, benzyl), a sulfur atom, or a carbonyl group was prepared and evaluated for antibacterial activity and inhibitory activity on DNA gyrase isolated from E . coli KL-16 . The in vitro antibacterial potency and DNA gyrase inhibitory activity were found to be in the following order: NMe > or = O > S >> C = O . Moreover, a methyl group was the optimal alkyl substituent at the 10-position nitrogen atom for antibacterial activity and for DNA gyrase inhibitory activity . 7-Fluoro-9,1-{(N-methylimino)methano}-8- (4-methyl-1-piperazinyl)-5-oxo-5H-thiazolo{3,2-alpha}quinoline-4-carboxy lic acid (10-NCH3) showed potent in vivo antibacterial activity.

Infect Immun, 1993 Sep, 61(9), 3775 - 84
Implication of phagosome-lysosome fusion in restriction of Mycobacterium avium growth in bone marrow macrophages from genetically resistant mice; de Chastellier C et al.; The ability of the host to resist infection to a variety of intracellular pathogens, including mycobacteria, is strongly dependent upon the expression of the Bcg gene . Mouse strains which express the resistance phenotype (Bcgr) restrict bacterial growth, whereas susceptible strains (Bcgs) allow bacterial growth . Expression of the Bcg allele is known to influence the priming of host macrophages (M phi s) for bactericidal function . In the present work, bone marrow-derived M phi s from congenic BALB/c (Bcgs) and C.D2 (BALB/c.Bcgr) mice were infected with the virulent strain Mycobacterium avium TMC 724 to define the mechanism involved in growth restriction of M . avium . By combining CFU measurements and ultrastructural analyses, we show that growth of this bacterium is restricted in marrow M phi s from resistant mice . Using acid phosphatase as a lysosomal marker, we provide evidence that the hydrolytic activity of M phi s, as measured by the capacity of lysosomes to fuse with and transfer active hydrolytic enzymes to phagosomes in which M . avium resides, is an expression of the Bcg gene and that this phenomenon is a key antibacterial activity responsible for growth restriction of M . avium: (i) the percentage of phagosome-lysosome fusions was twice as high in Bcgr M phi s as in Bcgs M phi s, and (ii) the percentage of intact viable bacteria residing in acid phosphatase-negative phagosomes was twice as low in Bcgr M phi s as in the Bcgs counterparts . These differences are not due to a lower activity of the enzyme in Bcgr M phi s . The mechanism by which the Bcg gene exerts control over the phagolysosomal fusion is discussed.

Pol Arch Med Wewn, 1993 Sep, 90(3), 218 - 25
{Tuberculosis in patients chronically treated with hemodialysis}; Rogowski R et al.; Tuberculosis (tbc) is a significant problem in view of diagnosis and therapy in patients on hemodialysis (HD) . The object of this study was to analyse cases of tbc found among patients treated by HD at the 1st Dept . of Internal Medicine, Central Railway Hospital in the years 1971-91 . Tuberculosis was found in 10 out of 182 patients eligible for analysis (5.5%), 7 of whom were men . Mean HD treatment time before diagnosis was 17 months (for the majority--less than 1 year) . One patient had pulmonary tbc 6 had pulmonary tbc with extrapulmonary involvement and 3 had extrapulmonary TB only . Six patients had pericardial involvement . Clinical examination revealed malaise, lack of appetite, weight loss, fever, cough . All cultures were negative . Tuberculin test were positive in only 2 cases . In 4 cases tbc was diagnosed on necropsy . In remaining cases tbc diagnosis was based on clinical grounds, X-ray films and ineffectiveness of broad spectrum antibacterial chemotherapy in conjunction with effective antimycobacterial chemotherapy . Agents used were: rifampicin, isoniazide, ethambutol . Out of 6 treated patients 5 showed improvement . Two patients had a tbc relapse . Mean yearly incidence in our material is 33 times higher than the mean yearly incidence in the general Polish population in the years 1971-91 . CONCLUSIONS: Patients on HD have a high incidence of tbc which presents diagnostic difficulties; extrapulmonary organ involvement is the rule in dialysed patients; tbc in such a setting may lead to death if untreated; effect of antimycobacterial therapy confirms diagnosis.

Zentralbl Bakteriol, 1993 Sep, 280(1-2), 253 - 8
Effects of substances inhibiting or uncoupling respiratory-chain phosphorylation of Helicobacter pylori; Baer W et al.; The effects of electron transport inhibitors and uncoupling agents as well as of bismuth compounds on the respiratory activity and oxidative phosphorylation of Helicobacter pylori were investigated . Bismuth gallate and bismuth subsalicylate reduced the respiratory chain-dependent phosphorylation . Inhibition was of the same magnitude as that observed with other known inhibitors . It is concluded that bismuth displays an antibacterial effect by inhibiting the respiratory chain of H . pylori.

Zentralbl Bakteriol, 1993 Sep, 280(1-2), 239 - 43
Antibacterial activity of teprenone, a non water-soluble antiulcer agent, against Helicobacter pylori; Ishii E; Teprenone, a non water-soluble antiulcer agent, is a derivative of terpene . The antibacterial activity of teprenone against Helicobacter pylori was examined by the disc method and survival test in albumin broth including teprenone . Growth of H . pylori around the disc charged with teprenone was inhibited on Brucella agar supplemented with bovine serum albumin fraction V, charcoal, or beta-cylodextrin, but not with blood or egg yolk emulsion . Furthermore, when H . pylori was exposed in broth including teprenone, H . pylori did not survive after 20 hours at 0.25 approximately 10 ppm . These results indicate that teprenone has antibacterial activity against H . pylori.

J Antimicrob Chemother, 1993 Sep, 32(3), 355 - 65
Antibacterial activities of non-antibiotic drugs; Cederlund H et al.; Antibacterial activities of several 'non-antibiotic drugs' used in treatment of a variety of non-infectious human diseases have been observed . Such an effect has been noticed for barbiturates, beta-adrenergic receptor antagonists, diuretic drugs, H1 antihistamines, mucolytic agents, nonsteroid anti-inflammatory drugs, proton pump inhibitors and psychotherapeutic drugs . A synergic or antagonistic effect with antibiotics of several of these drugs have also been noticed . In this overview the knowledge in the field is summarized, omitting hormones, drugs with local effects and those with low therapeutic indexes . Therapeutic implications and future considerations are discussed.

J Nat Prod, 1993 Sep, 56(9), 1444 - 50
An antifungal bibenzyl from the New Zealand liverwort, Plagiochila stephensoniana . Bioactivity-directed isolation, synthesis, and analysis; Lorimer SD et al.; The bioactivity-directed isolation of 4-hydroxy-3'-methoxybibenzyl {1} from a New Zealand liverwort, Plagiochila stephensoniana, is described . Compound 1 exhibited antifungal and antibacterial activity . Compound 1 is not considered to be a useful taxonomic marker . Syntheses of 1, stilbenes 2 and 3, and some derivatives were made and the biological activities were compared.

Am J Vet Res, 1993 Sep, 54(9), 1496 - 9
In vitro antibacterial activity of cefoxitin and cefotetan and pharmacokinetics in dogs; Petersen SW et al.; The susceptibility of 50 clinical Escherichia coli isolates to various antibacterials, including cefoxitin and cefotetan was ascertained, and the minimal inhibitory concentration (MIC) of cefoxitin and cefotetan for each of these isolates was determined . The pharmacokinetics of cefoxitin and cefotetan after a single i.v . or SC injection (30 mg/kg of body weight) were determined in 4 dogs . Of the 50 E coli isolates, 98% were susceptible in vitro to cefotetan, 90% were susceptible to cefoxitin, and 88% were susceptible to gentamicin . The MIC that would inhibit the growth of 90% of the E coli isolates (MIC90) was 0.25 microgram/ml for cefotetan and 4 micrograms/ml for cefoxitin . Plasma cefotetan concentrations remained above MIC90 for (mean +/- SD) 8.2 +/- 1.72 hours and 13.52 +/- 0.28 hours after i.v . and SC administration, respectively . Plasma cefoxitin concentrations remained above MIC90 for (mean +/- SD) 5.37 +/- 1.18 hours and 7.95 +/- 0.71 hours after i.v . and SC administration, respectively . We concluded that cefotetan was superior to cefoxitin in activity against E coli in vitro . We recommend that cefotetan be given at a dosage of 30 mg/kg, i.v., every 8 hours, or SC, every 12 hours.

Yakugaku Zasshi, 1993 Sep, 113(9), 676 - 81
{Studies on pyridazinone derivatives . XV . Oxidative reactions and antibacterial antifungal activity of sulfur derivatives of pyridazinone}; Takaya M; Oxidative reactions of o-nitrophenylthio substituted 2-phenyl-3(2H)-pyridazinones (3, 4, 13) with hydrogen peroxide were examined and o-nitrophenylsulfinyl compounds (5, 7, 14) and o-nitrophenylsulfonyl compound (6) were obtained . As the results of antibacterial antifungal screening tests in vitro, 3, 5 and 6 revealed strong antitrichophyton activities.

J Dairy Sci, 1993 Sep, 76(9), 2597 - 600
Forms of lactoferrin: their antibacterial effect on enterotoxigenic Escherichia coli; Dionysius DA et al.; The antibacterial effects of various forms of lactoferrin on enterotoxigenic strains of Escherichia coli were tested in vitro using a microassay for bacterial growth . Native and apo-lactoferrin exhibited variable activity against 19 strains, whereas holo-lactoferrin had no effect . At a concentration of .2 mg/ml of apo-lactoferrin, strains could be distinguished as either sensitive or resistant to inhibition . Zinc-saturated lactoferrin was as inhibitory as apo-lactoferrin when sensitive and resistant strains were tested over the concentration range .04 to 1.0 mg/ml of lactoferrin . A bactericidal effect was observed for native, apo-, and Zn-saturated lactoferrin against some sensitive strains . The antibacterial activity of apo-lactoferrin depended on bacterial inoculum size and was not enhanced by the addition of lysozyme . Addition of holo-lactoferrin or cytochrome c diminished the antibacterial effect of apo-lactoferrin, whereas addition of BSA had no effect . Resistance to inhibition by lactoferrin was not related to the production of bacterial siderophores.

AIDS, 1993 Sep, 7(9), 1205 - 12
Inactivation of HIV infectivity by the chlorite-oxygen reaction product tetrachlorodecaoxygen; Ennen J et al.; OBJECTIVE: Since the chlorite-oxygen reaction product tetrachlorodecaoxygen (TCDO) anion complex promotes efficaciously tissue repair and has antibacterial activity, our aim was to determine the effects of TCDO on the replication of HIV and on the infectivity of free HIV particles . DESIGN: The effects of TCDO on cellular HIV replication machinery and the consequences of TCDO for infectivity of HIV virions were evaluated . METHODS: Virus yields in supernatants of TCDO-supplemented cultures of HIV-infected cells or virus infectivity in TCDO-treated virus stocks were quantified by titration assays and then calculating the 50% tissue culture infectious dose . RESULTS: First, TCDO did not affect the replication of HIV in persistently infected lymphocytic and monocytic cell lines or in peripheral blood mononuclear cells . Second, supplementation of HIV stocks with TCDO markedly decreased the infectivity of HIV particles in a concentration dependent manner . Third, the binding of gp120 envelope glycoprotein of HIV-1 to cells is blocked by pre-incubation with TCDO . Fourth, the inhibition of HIV replication by the reverse transcriptase inhibitor 3'-azido-3'-deoxythymidine (zidovudine) in de novo infected cell cultures was not affected by the simultaneous addition of TCDO . However, the delayed virus spread of HIV in cultures in the presence of suboptimal concentrations of zidovudine could significantly be blocked by the simultaneous addition of TCDO . Fifth, TCDO failed to induce the chromosomally integrated HIV-1 provirus in the T-lymphoma cell line ACH2 . CONCLUSIONS: TCDO appears to inactivate HIV particles directly, but has no influence on the intracellular replicative machinery of HIV . Our results suggest that a clinical evaluation of the TCDO complex as chemotherapy for HIV infection and full-blown AIDS should be considered, particularly in patients concomitantly receiving zidovudine.

Trends Microbiol, 1993 Sep, 1(6), 232 - 5
On the mechanism of action of quinolone drugs; Palumbo M et al.; Antibacterial quinolones are thought to inhibit DNA gyrase by trapping the enzyme as a complex with the DNA substrate . The precise molecular details of drug-DNA and drug-enzyme interactions remain controversial . Here, a model is proposed that accounts for the influence of magnesium ions on quinolone-DNA binding.

Vestn Otorinolaringol, 1993 Sep-Dec, (5-6), 47 - 9
{Dimethyl sulfoxide in the treatment of patients with inflammatory diseases of external and middle ear}; Poliakova TS et al.; The combination of various drugs with midethyl sulfoxide (DS) solution has been tried in 49 patients with inflammation of the external ear and 10 patients with acute otitis media . It was found that DS solutions potentiate the effect of the drugs . A broad antibacterial and antimycotic spectrum, high transdermal, analgetic, antiinflammatory and potentiating potential in good side-effect profile made it possible to recommend DS for management of external and middle ear inflammation.

Acta Trop, 1993 Sep, 54(3-4), 251 - 60
Inhibition of topoisomerases in African trypanosomes; Shapiro TA; African trypanosomiasis continues to pose a challenge for the development of new chemotherapy . Type II topoisomerases, essential enzymes in nucleic acid metabolism, have proven highly suitable as targets for antibacterial and antitumor therapy . Well-characterized topoisomerase II inhibitors affect the cognate nuclear and mitochondrial enzymes in Trypanosoma equiperdum . Inhibition is accompanied by extensive fragmentation and structural alteration in nuclear and mitochondrial DNA . Some clinically important antitrypanosomal drugs bind to DNA (i.e., pentamidine, isometamidium, diminazene) . These agents inhibit the mitochondrial, but not nuclear, topoisomerase II of trypanosomes . These studies suggest that type II topoisomerase inhibitors may prove to be effective and safe new antitrypanosomal drugs.

J Chromatogr, 1993 Aug 27, 646(1), 175 - 84
Analytical methods for differentiating minor sequence variations in related peptides; Grieve PA et al.; A proline-rich peptide was isolated and purified to homogeneity from an extract of bovine neutrophil granules using semi-preparative RP-HPLC . The relative molecular mass of the peptide (called Bac-X) was determined by ionspray MS to be 5149 +/- 0.5 . The amino acid composition of the peptide was characterized by its limited number of amino acid types, which included a high proline (43.3%) and arginine content (20.3%), and hydrophobic residues . Bac-X had similar characteristics to Bac-5, a previously characterised bactenecin of bovine neutrophil granules, with respect to its proline, arginine and hydrophobic amino acid content, molecular mass and antibacterial specificity . Tryptic and N-bromosuccinimide digestion of Bac-X produced fragments with masses (M(r) 785 and 4224 and 3100 respectively) consistent with those expected from a peptide with the reported sequence of Bac-5 . Bac-X differed from Bac-5 in the number of amino acid residues (43 for Bac-X versus 42 for Bac-5) and contained glycine which Bac-5 did not . However, the calculated molecular mass of the peptide, based on the amino acid compositional data, did not match the experimental value . The purified peptide could not be sequenced by Edman degradation due to apparent blockage of the N-terminus . Partial sequence information, obtained by LC-MS and collision induced dissociation MS-MS analysis of a M(r) 785 tryptic fragment of Bac-X, showed that this peptide contained a six residue sequence (-RFPPIR-) not found in Bac-5 which, based on its reported sequence, contained a M(r) 785 tryptic fragment with the sequence -FRPPIR- . This difference in sequence of Bac-X compared with Bac-5 illustrates the application of electrospray (ionspray) MS techniques to the detection and identification of minor differences in related protein/peptide forms.

J Biol Chem, 1993 Aug 5, 268(22), 16458 - 64
Xenoxins, a family of peptides from dorsal gland secretion of Xenopus laevis related to snake venom cytotoxins and neurotoxins; Kolbe HV et al.; Three new, highly similar peptides from the skin secretion of Xenopus laevis have been purified and analyzed by mass spectrometry and Edman degradation . The 66-amino-acid peptides, termed xenoxin-1, -2, and -3, contain 8 cysteines and show similarity to snake venom cytotoxins and short neurotoxins . Assignment of two out of four disulfide bonds suggests a tertiary structure similar to that of cytotoxins and short neurotoxins . A cDNA encoding pre-xenoxin-1 was isolated from a X . laevis skin cDNA library . The nucleotide sequence predicts the synthesis of a precursor with a signal peptide followed by the sequence of the mature peptide . Xenoxin-1 and -2 lack alpha-neurotoxic activity, have apparently no antibacterial activity, are low in general toxicity as tested in mice, and have no effect on blood coagulation as measured in a Factor VIII procoagulant activity test . Potential functions of xenoxins as well as evolutionary aspects are discussed.

J Appl Bacteriol, 1993 Aug, 75(2), 108 - 12
Effects of low concentrations of ampicillin in feed on the intestinal Escherichia coli of chicks; al-Sam S et al.; Ampicillin in low concentrations (1.7 and 5 g t-1) was incorporated in the feed given to 1-d-old chicks for 2 weeks . This was sufficient to select, in the intestinal contents, resistant Escherichia coli strains for which the minimum inhibitory concentration of ampicillin was > 100 micrograms ml-1 . Different clones of E . coli were identified by their biotype, pattern of resistance to antibacterial agents and plasmid profile (designated P-P types) . The experiment was repeated twice and the average proportion of ampicillin-resistant P-P types among 72 isolates of E . coli from chicks given feed containing 0, 1.7 and 5 g ampicillin t-1 were 10%, 31% and 46% respectively.

J Antibiot (Tokyo), 1993 Aug, 46(8), 1279 - 88
Synthesis and biological activity of 3-(N-substituted pyridinium-4-thiomethyl)-7 alpha-formamido cephalosporins; Guest AW et al.; The synthesis and antibacterial activity of a series of 3-(1-substituted pyridinium-4-thiomethyl)-7 alpha-formamido cephalosporins is described . All the derivatives showed good potency and stability to bacterial beta-lactamases . The antibacterial efficacy seen with the N-alkyl pyridinium substituents was enhanced by the introduction of a catecholic side chain at C-7 and by preparation of N-(substituted amino)pyridinium derivatives.

J Antibiot (Tokyo), 1993 Aug, 46(8), 1239 - 45
9a,11-cyclic carbamates of 15-membered azalides; Kobrehel G et al.; The novel 9a,11-cyclic carbamates (13-15) of 9-deoxo-9a-aza-9a-homoerythromycin A (4) have been prepared and characterized by 1H-1H and 1H-13C 2D NMR spectroscopy . When compared to azithromycin (1) or its 6-O-methyl derivative (2), the new bicyclic 15-membered azalides exhibited substantially decreased antibacterial activities in vitro.

Jpn J Cancer Res, 1993 Aug, 84(8), 906 - 13
Brefeldin A blocks the cytotoxicity of T cell receptor alpha/beta and gamma/delta cytotoxic T lymphocyte clones reacting against human autologous cancer cells; Wada Y et al.; We studied the effector mechanism of T cell receptor (TCR) alpha/beta- and gamma/delta-type cytotoxic T lymphocyte (CTL) clones that react with human autologous tumor cells . Treatment of tumor cells with a fungal antibacterial reagent, brefeldin A (BFA), resulted in the inhibition of cytotoxicity of an autologous tumor (HST-2)-specific CD8+ TCR alpha/beta-type CTL, TcHST-2 . Other anti-metabolites such as chloroquine, cycloheximide and colchicine did not affect the cytotoxicity . The cell-surface antigen expression, including MHC class I molecules, was not influenced by BFA treatment . Furthermore, BFA did not influence the cytotoxicity of lymphokine-activated killer cells and natural killer cells . Since BFA blocks the transport of peptides from endoplasmic reticulum to the Golgi apparatus, the above data suggest that BFA could affect washing out of the peptide fragments from the MHC class I groove . Consequently, target tumor cells were protected from killing by CTL . Moreover, we obtained a CD4-, 8-, TCR gamma/delta-type (V delta 1+) CTL clone, TcHOT, that reacts against an autologous ovarial carcinoma, HOT . BFA could also inhibit this cytotoxicity, and it is likely that different presenting molecules other than MHC class I proteins participate in the cytotoxicity of this TCR gamma/delta-type CTL . These studies suggest that both TCR alpha/beta- and gamma/delta-type CTL may require antigenic peptides that are most likely derived from the BFA-sensitive, intracellular endogenous target proteins.

Pharmacology, 1993 Aug, 47(2), 135 - 40
Studies on the mechanism of action of colloidal bismuth subcitrate . I . Interaction with sulfhydryls; Beil W et al.; The present study was designed to examine the reaction pathway of colloidal bismuth subcitrate (CBS) with thiols . Studies were performed using the monothiol glutathione (GSH), the dithiol dithiothreitol (DTT) and the thiol enzymes papain and H+/K(+)-ATPase . UV-vis spectra showed that CBS forms complexes with GSH and DTT . The GSH/CBS complex but not the DTT/CBS complex was cleared by 5,5'-dithiobis-(2-nitrobenzoic acid) . CBS inhibited H+/K(+)-ATPase (IC50: 23 +/- 6.5 mumol/l) but failed to inhibit papain activity . The inhibitory action of CBS on H+/K(+)-ATPase-mediated proton transport was prevented by the dithiol dithioerythritol but not by GSH . These results indicate that CBS forms stable complexes with dithiols and instable complexes with monothiols . We suggest that some of the effects of CBS (i.e., stimulation of prostaglandin production, antibacterial action against Helicobacter pylori) are mediated via the blockade of SH-groups.

FASEB J, 1993 Aug, 7(11), 1011 - 5
Intracellular parasitism of Legionella and signaling in eukaryotic cells; Belyi YF; In this review the phenomenon of antibacterial activity of phagocytes and its relationship to the general system of signal transduction in eukaryotic cells is examined . Data are reviewed that support the hypothesis that interference in transduction of regulatory signals during microbial invasion could be caused by specific bacterial products and lead to an inadequate bactericidal response, and hence multiplication of the bacteria in a host . In this connection, information concerning virulence factors of the facultative intracellular parasite Legionella is discussed.

Int Dent J, 1993 Aug, 43(4 Suppl 1), 375 - 86
Hygiene and health: the value of antiplaque agents in promoting oral health; Johnson NW; The improvements in human health and increased life expectancy which have come about in many societies in the past century have been due, predominantly, to improvements in hygiene--both personal and environmental . As the common oral diseases--caries and gingivitis and to some extent periodontitis--are bacterially mediated diseases, they are also amendable to control by oral hygiene . As commonly practised however, with modern diets, mechanical oral hygiene alone has limited effect on disease incidence . The supplementation of tooth brushing with chemical agents which modulate plaque metabolism and the effects of metabolites on the hard and soft tissues of the dento-gingival structures certainly has preventive and therapeutic value . This is particularly true of fluoridated dentifrices in the control of dental caries, and of dentifrices with antibacterial and anticalculus properties, such as those containing low concentrations of the phenolic compound Triclosan, in the control of gingivitis . Microbial colonisation of tooth and other body surfaces is normal and forms part of the natural defence against dangerous exogenous organisms: thus modulating or 'controlling' plaque, not eliminating it, is the purpose of oral hygiene . The goal is to maintain a microbial ecosystem consistently associated with healthy tissues.

J Oral Pathol Med, 1993 Aug, 22(7), 303 - 7
Keratinocyte expression of calprotectin in oral inflammatory mucosal diseases; Eversole LR et al.; Oral mucosal inflammation evolves in response to microbial pathogens and non-infectious antigens which activate humoral and cell-mediated immunologic processes . Most of these disease processes invoke a leukocyte response culminating in cellular infiltration of the submucosa and, to some degree, transmigration into the epithelium itself . Calprotectin, a leukocyte-derived dimeric protein complex that has potent antibacterial and antifungal effects, has recently been identified in skin and mucosal keratinocytes implying that epithelium may biochemically contribute to the overall mechanism of host defense . In this study, the upregulation of calprotectin as assessed immunohistochemically is pursued for oral diseases of immunopathologic, fungal and viral origin . In lichen planus, candidiasis, herpes virus stomatitis, and oral hairy leukoplakia, calprotectin was found to be expressed to a significantly higher level than in normal control mucosal samples.

Immunopharmacol Immunotoxicol, 1993 Aug, 15(4), 447 - 59
Effectiveness of thymostimulin and study of lymphocyte-dependent antibacterial activity in children with recurrent respiratory infections; De Mattia D et al.; Recurrent respiratory infections (RRI) consist of more relapsing acute respiratory infections than the ones expected for the age {> 6 acute respiratory tract infections (RTI) per year if age is > 3 years, and > 8 acute RTI per year if age is < 3 years} . Concerning the pathogenesis of RRI, several investigations report the important role of environmental factors, early socialization and immunological dysfunctions, such as lymphocyte subpopulations alterations, IgG subclass deficiency and phagocytosis and/or opsonization deficit during acute infections . In this framework, we have studied the lymphocyte-dependent antibacterial activity (ABA) among 121 children affected by RRI . Results show a statistically significant alteration of this function in 38 children (31.4%): 19 of them exhibited an absent ABA (group 1), while in the others same function was reduced (group 2) . A bovine thymic extract, thymostimulin, was administered to both groups by intramuscular injections (1 mg/kg) for a 3 month cycle . At the end of therapy we observed a statistical significant rise of ABA only in group 1 and among children aged > 3 years . Among the same patients, 33 children (86.8%) improved in terms of reduction of clinical score and better results were seen among children aged > 3 years . These data emphasize the beneficial role of thymostimulin in RRI-affected children, suggesting a transient immaturity of the immune system as one of the possible pathogenetic factor.

Immunopharmacol Immunotoxicol, 1993 Aug, 15(4), 415 - 28
In vivo effects of alprazolam and lorazepam on the immune response in patients with migraine without aura; Covelli V et al.; Over the past few years, the immunomodulating role of benzodiazepines (BDZ) has been reported in literature . In particular, diazepam is an inhibitory BDZ with regard to its effects on the phagocytic and metabolic activities of polymorphonuclear cells (PMN) and monocytes, while triazolobenzodiazepines (alprazolam and triazolam) upregulate normal human peripheral blood T lymphocyte function . On these grounds, the administration of alprazolam (1 mg/per day for 1 month) in 13 patients with migraine without aura (MWA) and of lorazepam (2 mg/per day for 1 month) in 10 matched MWA subjects has been evaluated in terms of immune response . Results show that before administration of BDZ in both groups of patients phagocytosis and killing of PMN and monocytes were profoundly depressed and the same was true for the lymphocyte-dependent antibacterial activity . After one month treatment lorazepam further decreased lymphocyte function without modifying phagocytic capabilities . On the contrary, alprazolam increased PMN phagocytosis and killing and monocyte phagocytosis without modifying antibacterial activity values . Taken together, these results further support the existence of different classes of BDZ in terms of their immunomodulating capacities . Moreover, alprazolam seems to be a more appropriate BDZ for treating immunocompromised patients, even including MWA patients.

J Antimicrob Chemother, 1993 Aug, 32(2), 301 - 5
Bactericidal effect of gentamicin peak concentration provides a rationale for administration of bolus doses; McLean AJ et al.; A study was made of the influence of peak gentamicin concentration (Cmax) independent of the area under the antibiotic concentration-time curve (AUC) on the bactericidal effect of gentamicin against Escherichia coli NCTC 10418 . Bacteria in the lag phase were exposed to in-vitro gentamicin concentration-time profiles which modelled complete profiles determined in vivo in patients after an intravenous bolus (1 min) or infusion (30 min) regimen . An additional in-vitro profile reflected antibiotic removal 30 min after bolus dosing . Bacterial viable cell counts and gentamicin concentrations were measured before and during antibiotic exposure . Both Cmax and AUC were shown to be factors determining antibacterial activity; however Cmax independently represented some 35% of total exposure effect . These findings indicate grounds for preferring bolus intravenous gentamicin dosing with appropriate attention to potential toxicity.

J Antimicrob Chemother, 1993 Aug, 32(2), 195 - 213
The accumulation of five antibacterial agents in porin-deficient mutants of Escherichia coli; Mortimer PG et al.; A library of isogenic mutants containing Mud9-induced deletions of the structural and regulatory genes for the porin proteins OmpF and OmpC of Escherichia coli was constructed . The accumulation of norfloxacin, tetracycline, chloramphenicol, cephalothin and cefoxitin was measured with each strain, and shown to be reproducible with low experimental standard deviations, such that the roles of OmpF, OmpC and PhoE in the accumulation of these agents were determined . All data were statistically analysed to determine whether the differences observed between the data for each mutant compared with those for the other mutants and for the wild-type strain were significant . The loss of OmpF reduced accumulation of norfloxacin, tetracycline, cephalothin and cefoxitin by 16-60% compared to the wild-type parent strain, but reduced accumulation of chloramphenicol by < 10% . The loss of OmpC reduced accumulation of cephalothin and cefoxitin by 13 and 34%, respectively, compared to the wild-type parent strain, but had little effect on the accumulation of norfloxacin, chloramphenicol and tetracycline (< 3%) . The loss of both OmpF and OmpC (ompR) reduced accumulation of norfloxacin, chloramphenicol, tetracycline, cephalothin and cefoxitin by 36-68% . However, the presence of PhoE in the absence of both OmpF and OmpC, enhanced accumulation to 52-119% of the concentrations of these five agents accumulated by the wild-type strain . These data suggest that OmpF is the preferred route of entry for three of the antibiotics studied, but not for chloramphenicol and tetracycline which utilize both porins equally well . The high levels of accumulation (30-64%) of all five antibiotics in the absence of all major porins suggest that an alternative mechanism(s) of accumulation is available.

Chest, 1993 Aug, 104(2), 481 - 6
In vitro effect of beta 2-agonists on bacterial killing and superoxide anion (O2-) release from alveolar macrophages of patients with chronic bronchitis; Capelli A et al.; A new class of long-acting beta 2-adrenoceptor agonists has been studied in the last few years . Apparently, they display an important anti-inflammatory activity with an inhibition of different cellular functions . This study was carried out to compare a long-acting beta 2-agonist, formoterol, with a conventional short-acting one, salbutamol, on the release of superoxide anion (O2-) and bacterial killing by alveolar macrophages obtained with bronchoalveolar lavage (BAL) from 20 patients with chronic bronchitis . The O2- production in basal conditions was not affected by beta 2-agonists . On the contrary, after phagocytosis of opsonized zymosan 10(-5) M formoterol significantly affected the phagocytic index (difference between stimulated and basal O2- release): 7.9 +/- 2.0 nM O2-/10(6) AM/10 min vs 16.8 +/- 2.5, p < 0.0007 . Bacterial killing was inhibited by the two drugs in a dose-dependent way, but the effect of formoterol was more evident than that of salbutamol . After blocking beta 2-receptors with propranolol, we observed a prevention of the beta 2-agonist effects on both O2- release and bacterial killing . The inhibition of the alveolar macrophage functions considered in this study is evident for both beta 2-agonists, but it is significantly more pronounced for formoterol . Our data can be interpreted as one possible mechanism of the anti-inflammatory effect described for long-acting beta 2-agonists . On the other hand, also a potential suppression of pulmonary antibacterial defenses must not be overlooked, particularly in chronic bronchitis, a disease characterized by recurrent airways infections . Whether current therapeutic dosages are sufficient to achieve anti-inflammatory or microbicidal suppressive effects of clinical relevance has not been demonstrated so far.

Antibiot Khimioter, 1993 Aug-Sep, 38(8-9), 3 - 10
{Antibiotic production by inactive cultures of actinomycetes after treatment with ethidium bromide}; Malkina ND et al.; Inactive strains of actinomycetes isolated from natural sources were treated with ethidium bromide, an intercalating agent . After the treatment the cultures formed active variants at a frequency of more than 0.1 per cent which was rather high . 41 out of 93 cultures formed variants active against gram-positive bacteria . The majority of the active variants synthesized antibiotics only on agarized media . Daunorubicin was also used as an intercalating agent and shown to induce at a high frequency the formation of active variants with the same antibacterial spectrum as the variants induced by ethidium bromide . Induction of antibiotic production by the intercalating agents in the inactive strains of actinomycetes was likely due to the activation of the silent genes responsible for the biosynthesis of secondary metabolites.

J Chromatogr, 1993 Jul 23, 643(1-2), 369 - 78
Liquid chromatographic analysis of antibacterial drug residues in food products of animal origin; Shaikh B et al.; This paper reviews recent developments in the liquid chromatographic (LC) methods of analysis for the residues of antibiotics (aminoglycosides, chloramphenicol, sulfonamides, tetracyclines, macrolides, beta-lactams, etc.) in food products of animal origin . The review also covers clean-up procedures, such as, ultrafiltration, liquid-liquid partition, solid-phase extraction, immunoaffinity, and matrix solid-phase dispersion, for use as extraction, deproteination, and concentration steps . The LC methods offer considerable potential for rapid automated analysis, and some may be used as direct screening for residues in meat and milk.

Biochem Biophys Res Commun, 1993 Jul 15, 194(1), 347 - 50
Evidence for the release and possible neural regulation of nitric oxide in human saliva; Bodis S et al.; We report the presence of nitric oxide (NO) as measured through its product NO2 in human saliva . The presence of NO is not due to oral bacterial activity but is due to a genuine release of NO from the salivary glands and can be detected in freshly secreted saliva collected from a mouth freshly rinsed with an antiseptic preparation to reduce the bacterial content significantly . In order to study the regulation of salivary NO we used lemon juice to increase salivary flow and detected an immediate transient reduction of salivary NO2 which rose to levels equal to and sometimes higher than basal levels in five minutes in most donors indicating salivary NO production might be under neural control . Salivary NO production may play a physiological role in both the natural antibacterial properties of salivary secretion and possibly in detoxification of oral carcinogens.

Biochem Biophys Res Commun, 1993 Jul 15, 194(1), 17 - 22
Purification and characterization of a scorpion defensin, a 4kDa antibacterial peptide presenting structural similarities with insect defensins and scorpion toxins; Cociancich S et al.; Insect defensins are a group of inducible small-sized antibacterial peptides with three intramolecular disulfide bridges . NMR studies have recently shown that they share striking structural similarities with scorpion toxins . We have investigated in a scorpion species, Leiurus quinquestriatus, the potential presence of antibacterial molecules and report the isolation and structural characterization of a novel insect defensin homologue, which we refer to as scorpion defensin . This peptide shows a remarkably high degree of sequence homology with a defensin recently characterized in a species belonging to the ancient insect order of the Odonata with which it defines a novel ancient subclass of defensins . The scorpion defensin has in common with the scorpion toxins a consensus sequence Cys-{...}-Cys-Xaa-Xaa-Xaa-Cys-{...}-Gly-Xaa-Cys-{...}-Cys-Xaa-Cys present in all scorpion toxins characterized so far.

J Biol Chem, 1993 Jul 15, 268(20), 14893 - 7
A novel inducible antibacterial peptide of Drosophila carries an O-glycosylated substitution; Bulet P et al.; One of the facets of the host defense of higher insects is the rapid and transient synthesis, following bacterial challenge or trauma, of a battery of potent antibacterial peptides (Steiner, H., Hultmark, D., Engstrom, A., Bennich, H., and Boman, H . G . (1981) Nature 292, 246-248) . The best characterized of these peptides are the cecropins (ibid.), 4-kDa peptides devoid of cysteines, and the insect defensins (Hoffmann, J . A., and Hetru, C . (1992) Immunol . Today 13, 411-415), 4-kDa peptides with three intramolecular disulfide bridges . Several other inducible antibacterial peptides have been characterized only at the level of their amino acid sequences (Hoffmann, J . A., Dimarcq, J . L., and Bulet, P . (1992) Medecine & Sciences 8, 432-439) . We report here the isolation of a novel 19-residue proline-rich inducible antibacterial peptide from Drosophila . In contrast to all previous reports on antibacterial peptides, this molecule carries a substitution as evidenced by molecular mass determinations; our data show that this reflects the O-glycosylation of a Thr residue by an N-acetylgalactosamine plus a galactose . A synthetic nonsubstituted peptide of identical amino acid sequence has an activity several times lower (5-10) than the native compound . Our data suggest that this substitution represents a post-translational modification essential for the full biological activity of this novel peptide.

J Med Chem, 1993 Jul 9, 36(14), 1964 - 70
Quinolone antibacterials: synthesis and biological activity of carbon isosteres of the 1-piperazinyl and 3-amino-1-pyrrolidinyl side chains; Laborde E et al.; A series of 6-fluoro-1,4-dihydro-4-oxo-3-quinoline- and 1,8-naphthyridinecarboxylic acids, substituted at the 7-position with carbon-linked side chains, was synthesized and evaluated for antibacterial activity and DNA-gyrase inhibition . Structural modifications focused on replacement of the heterocyclic nitrogen of the frequently found 1-piperazinyl and 3-amino-1-pyrrolidinyl side chains by an sp2- or an sp3-hybridized carbon . All new compounds displayed high in vitro and in vivo antibacterial activity . Potency relative to the standard nitrogenated agents was dependent on ring size and hybridization of the linking carbon atom of the side chain . Compounds with a 1,2,3,6-tetrahydro-4-pyridinyl substituent at C-7 were equipotent with their 1-piperazinyl analogs, whereas those having a 4-piperidinyl or a 3-amino-1-cyclopentenyl ring at C-7 were less active than the 1-piperazinyl or 3-amino-1-pyrrolidinyl substituted agents, respectively . This relative difference in antibacterial potency did not correlate with the observed activity against gyrase, where the majority of the new compounds were equally or more potent than their nitrogenated counterparts.

Infect Immun, 1993 Jul, 61(7), 2978 - 84
Mechanisms of action on Escherichia coli of cecropin P1 and PR-39, two antibacterial peptides from pig intestine; Boman HG et al.; Cecropin P1 and PR-39 are two antibacterial peptides isolated from the upper part of the small intestine of the pig . They have been sequenced, and their antibacterial spectra have been investigated (J.-Y . Lee, A . Boman, C . Sun, M . Andersson, H . Jornvall, V . Mutt, and H . G . Boman, Proc . Natl . Acad . Sci . USA 86:9159-9162, 1989; B . Agerberth, J.-Y . Lee, T . Bergman, M . Carlquist, H . G . Boman, V . Mutt, and H . Jornvall, Eur . J . Biochem . 202:849-854, 1991) . We have now compared these two peptides for their mechanism of action on Escherichia coli K-12 by using three strains with different markers . Our results show that cecropin P1, like other cecropins, kills bacteria by lysis and that this reaction requires more peptide to kill more cells . PR-39 requires a lag period of about 8 min to penetrate the outer membrane of wild-type E . coli; then killing is quite fast . This lag period was absent in the envA1 mutant; in this strain the outer membrane was freely permeable to both peptides . PR-39 killed growing bacteria faster than nongrowing cells; for cecropin P1 there was no such difference . It is suggested from isotope incorporation experiments that PR-39 kills bacteria by a mechanism that stops protein and DNA synthesis and results in degradation of these components.

Mol Plant Microbe Interact, 1993 Jul-Aug, 6(4), 453 - 66
Spatial and temporal accumulation of defense gene transcripts in bean (Phaseolus vulgaris) leaves in relation to bacteria-induced hypersensitive cell death; Meier BM et al.; Primary leaves of 7- to 9-day-old Red Mexican bean plants were inoculated with virulent or avirulent isolates of Pseudomonas syringae pv . phaseolicola, or saprophytic P . fluorescens either by vacuum infiltration of the whole leaf lamina, or by syringe-inoculation of selected leaf panels . In the incompatible combination, resistance was associated with a hypersensitive response (HR) . Syringe-inoculated leaves were sampled in three zones: zone 1, the inoculated leaf area; zone 2, the surrounding 0.5-0.7 cm of leaf tissue; and zone 3, the remainder of the leaf . Northern blots of RNA from zones 1, 2, and 3 were probed with bean cDNAs for phenylalanine ammonia-lyase (PAL), chalcone synthase (CHS), chitinase (CHT), and lipoxygenase (LOX) . Accumulation of PAL, CHS, and CHT transcripts was more rapid and generally of greater magnitude in the incompatible than in the compatible interaction and, in both cases, was observed essentially only in zone 1 tissues . Similarly, antibacterial phytoalexins were only detected in zone 1 from the incompatible interaction . Young primary leaves have a background level of LOX transcripts, which declines as leaves age . This decline was accelerated over the first 12 hr postinoculation (hpi) with avirulent bacteria, whereas a weak transient induction, peaking at 5-6 hpi, was observed in the compatible interaction . A subsequent, strong accumulation of LOX transcripts was seen in both the compatible and incompatible interactions outside the inoculation site starting about 14 hpi . LOX transcripts did not accumulate at the inoculation site itself in the incompatible interaction compared to a relatively strong induction in the compatible interaction . Interestingly, inoculation of leaves with cells of the saprophyte P . fluorescens also induced the accumulation of transcripts for CHS, CHT, and LOX, but generally to a lesser degree than in the incompatible interaction . No HR occurred and no macroscopic cell damage was apparent in leaves inoculated with P . fluorescens . However, at the microscopic level individual, trypan blue-stained, necrotic plant cells were visible . In spite of this and the accumulation of CHS transcripts, no phytoalexin accumulation was found up to 48 hr after inoculation . The spatial and temporal relationship of the hypersensitive reaction to defense gene transcript and phytoalexin accumulation is discussed.

Am J Perinatol, 1993 Jul, 10(4), 269 - 71
Primary cutaneous aspergillosis in a preterm infant; Perzigian RW et al.; A case of primary cutaneous aspergillosis in a very low birthweight infant that responded to medical therapy is reported . Knowledge of the potential pathogenic role of this organism in neonatal skin lesions is important because of resistance to standard empirical antibacterial therapy and the potential for dissemination and deep parenchymal invasion . Surgical excision may be necessary if cutaneous aspergillosis progresses despite systemic antifungal therapy.

FEMS Microbiol Lett, 1993 Jul 1, 110(3), 331 - 4
Nourseothricin (streptothricin) inactivated by a plasmid pIE636 encoded acetyl transferase of Escherichia coli: location of the acetyl group; Zahringer U et al.; Escherichia coli strains harbouring the plasmid pIE636 are able to synthesize acetylcoenzyme A: streptothricin acetyltransferase (ACSAT) . The (enzymatic) N-acetylation of streptothricin F is known to contribute significantly towards the loss of antibacterial activity . 13C-NMR analysis of {14C}N-acetyl-labelled streptothricin F, produced by ACSAT-catalysed acetylation of streptothricin F and subsequent purification by various chromatographical steps, unequivocally revealed streptothricin F to be acetylated at the beta-amino group (C16) (and not at the epsilon-amino group (C19)).

Z Gastroenterol, 1993 Jul-Aug, 31(7-8), 450 - 8
{Clinico-pharmacologic considerations in Helicobacter pylori eradication therapy}; Leiss O et al.; Problems and pitfalls of treatment regimens for eradication of Helicobacter pylori (Hp) are discussed from a clinical, pharmacological and microbiological point of view . Problems concerning the physician who treats the patient consists mainly in inappropriate indication and suboptimal knowledge of drugs, doses and duration of therapy against Hp . For successful triple therapy with complicated dosage protocols cooperation with and compliance by the patient is stressed . Physicochemical, pharmacological and pharmacokinetic properties of bismuth salts and antibiotics as well as physiological aspects of pH and motility in the stomach must be considered in order to achieve optimal antibactericidal concentrations in the special micro milieu of Hp in the mucus/on the mucosa of the stomach . In addition, present pretreatment resistance of Hp against antibiotics and possible acquired resistance during antibiotic treatment are important aspects . Successful eradication of Hp mainly depends on the physician's clinical and pharmacological knowledge of bismuth salts and antibiotics, on considerations of microbiological aspects of Hp, on good doctor-patient-relationship and compliance by the patient.

Mikrobiyol Bul, 1993 Jul, 27(3), 216 - 20
{In vitro susceptibility to cefoperazone and sulbactam/cefoperazone combination of bacterial strains isolated from various patient materials}; Aksoy AM et al.; Susceptibility of 110 bacterial strains isolated from clinical materials to Cefoperazone (CPZ) and Sulbactam/Cefoperazone (SBT/CPZ) combination was investigated and every strain was examined for beta-lactamase activity . Total beta-lactamase positivity rate was 40.9% . Antibacterial activity of SBT/CPZ combination was found to be higher than CPZ alone, especially on beta-lactamase producing bacteria.

Insect Biochem Mol Biol, 1993 Jul, 23(5), 591 - 8
Purification and primary structure of ceratotoxin A and B, two antibacterial peptides from the female reproductive accessory glands of the medfly Ceratitis capitata (Insecta:Diptera); Marchini D et al.; In the present article we report the purification and the amino acid sequence of two antibacterial peptides present in the secretion of the female reproductive accessory glands of the dipteran insect Ceratitis capitata . Both peptides consist of 29 amino acid residues, are heat stable, strongly basic and differ from each other for the substitution of two amino acids . Their primary sequence and predicted secondary structure are related to other families of peptides known to have lytic and/or antibacterial activity . We propose the name ceratotoxins (from Ceratitis) for these antibacterial peptides.

Int J Dermatol, 1993 Jul, 32(7), 533 - 6
In vitro susceptibility of dermatophytes to antifungal drugs: a comparison of two methods; Macura AB; BACKGROUND . There is an evidence that some fungal strains are resistant to certain antimycotic drugs with resulting therapeutic failures . Unlike testing of antibacterial agents, the activity of these drugs against the given fungal strains is not tested routinely . The paper presented is an approach to such a procedure . METHODS . The minimum inhibitory concentration (MIC) values obtained using the dilution method were compared with the diameters of growth inhibition zones using the disk-diffusion method . Seven antifungal drugs (griseofulvin, natamycin, naftifine, clotrimazole, bifonazole, miconazole, ketoconazole) were tested with 80 fungal strains, including Trichophyton rubrum, T . mentagrophytes, Microsporum canis, and Epidermophyton floccosum . RESULTS . The majority of fungal strains were inhibited by griseofulvin at concentrations not exceeding 10 mg/L . The least susceptible was T . mentagrophytes . The most effective drug was naftifine, and the least effective was natamycin . Naftifine inhibited 98.75% of the strains tested at a concentration not exceeding 1.0 mg/L . An increase of the MIC value was accompanied by a decrease in the growth inhibition diameter . The relation was statistically significant . CONCLUSIONS . T . rubrum strains are more susceptible to antifungal drugs than T . mentagrophytes . Naftifine proved to be the most effective drug in dermatophytoses . Natamycin is a useful drug against yeast-like fungi but not against dermatophytes . The disk-diffusion method of fungal susceptibility assessment yields data consistent with results obtained from the dilution method and is recommended for routine use because of its simplicity.

Khirurgiia (Mosk), 1993 Jul, (7), 35 - 8
{Differentiated treatment of generalized peritonitis}; Karimov ShI et al.; The article discusses the results of treatment of 327 patients with generalized peritonitis in the toxic and terminal stages . The patients were divided conditionally into three groups . In the first group (42 patients) treatment consisted in routine cleansing of the abdominal cavity with drainage and introduction of antibiotics into it in the postoperative period . Mortality was 45.7%, complications occurred in 52.6% of patients who had survived . In the second group (145 patients) peritoneal dialysis in the flow-drip regimen was applied 3 or 4 times per 24 hours in a volume of 3-4 liters . In this group mortality was 37.9%, the number of complications among the survivals was 41.1% . In the third group (140 patients) a complex of differentiated peritoneal therapy was employed, including the following developed methods: thorough intraoperative cleansing of the abdominal cavity with 10-15 liters of antiseptic solutions containing antibiotics chosen according to the results of express-bacterioscopy, "active" peritoneal dialysis in the flow-fraction regimen, as well as developed methods of laparostomy--controlled laparostomy, prolonged open administration with local cleansing and use of antibacterial ointments . With use of this complex, mortality reduced to 27.1% and the incidence of complications to 20.6%.

Stomatologiia (Mosk), 1993 Jul-Sep, 72(3), 4 - 7
{Periodontal function and nonspecific resistance in the dynamics of experimental hypo- and hyperthyroidism}; Moskvina TS et al.; Morphologic study of white rat periodontal tissue and assessment of nonspecific resistance of the body by whole blood antibacterial activity, skin bactericidal activity, blood serum and mixed salivary lysozyme activity were carried out over the course of experimental hypo- and hyperthyrosis starting from day 5 to day 90 . The detected pathologic changes in the periodontium were in line with the time course of nonspecific resistance of the body . In hypothyrosis an earlier depression of nonspecific resistance factors was parallelled by earlier and more marked inflammatory destructive processes in the rat periodontium as compared to that in hyperthyrosis.

J Antimicrob Chemother, 1993 Jul, 32(1), 117 - 22
Absorption of oral ofloxacin after cytotoxic chemotherapy for haematological malignancy; Brown NM et al.; Ten patients with newly diagnosed haematological malignancy were given ofloxacin, 400 mg daily orally, for antibacterial prophylaxis during neutropenia . Before cytotoxic chemotherapy was given, and on three occasions between days 2-3, 5-7 and 8-10 afterwards, blood samples were taken before and 1, 2, 3, 4, 6 and 10 h after administration of ofloxacin . Serum ofloxacin concentrations were measured by HPLC . Mean (range) pharmacokinetic parameters before chemotherapy were: Cmax, 6.1 (2.7-9.1) mg/L; AUC0-2, 7.5 (1.9-11.6) mg.h/L . On days 2-3 post-chemotherapy the values were reduced to: Cmax, 5.0 (3.6-7.3) mg/L; AUC0-2, 5.8 (1.9-7.8) mg.h/L . On days 5-7 the values were: Cmax, 6.1 (4.0-10.4) mg/L; AUC0-2, 8.5 (0.8-16.8) mg.h/L, and by days 8-10 the values were: Cmax, 6.4 (3.3-12.5) mg/L; AUC0-2, 8.6 (0.8-23.1) mg.h/L . There was a statistically significant difference between Cmax pre- and Cmax two to three days post-chemotherapy (paired t-test, P = 0.05) . These changes are similar to those previously reported with ciprofloxacin but less marked.

Infection, 1993 Jul-Aug, 21(4), 229 - 34
Penetration of ceftazidime into human pancreas; Drewelow B et al.; The use of antibiotics in patients with severe acute pancreatitis (stage II and III) is indicated since bacterial complications are the most common cause of death in these patients . In the present study the penetration of ceftazidime into pancreatic juice, into healthy and chronically inflamed pancreatic tissue as well as into necrotic regions in cases of severe acute pancreatitis was investigated . A peak concentration of 12.9 +/- 5.9 mg/l was found 60 min after intravenous administration of 35 mg/kg of the drug, which is 32% of the corresponding serum levels . Pancreatic tissue concentrations varied between 9 and 79% of the corresponding serum levels, depending on the stage of inflammation . After five days of antibiotic treatment with doses of 2 g t.i.d., concentrations between 1.8 and 6.9 mg/kg were detected even in pancreatic necroses . This suggests that sufficient antibacterial levels of ceftazidime were present in all pancreatic compartments analyzed following administration of common therapeutic dosages . Therefore, from a pharmacokinetic point of view, ceftazidime could be a potentially effective drug for the treatment of pancreatitis.

Age Ageing, 1993 Jul, 22(4), 256 - 9
Role of serology in monitoring treatment for Helicobacter pylori infection in elderly patients; Safe AF et al.; Fifteen elderly patients with type B gastritis caused by Helicobacter pylori infection were treated with triple therapy consisting of colloidal bismuth subcitrate, amoxycillin and metronidazole . All were followed up every 6 weeks for 3 months . After triple therapy, eradication of the infection was confirmed in 12 patients (85%) by histology and bacteriology . In this group, a significant reduction in IgG antibody levels against H . pylori was detected (p < 0.001) . In a control group of 15 patients with type B gastritis who received no antibacterial treatment, the specific IgG antibody titre remained unchanged during 3 months of follow-up . We conclude that this simple and noninvasive serological test would be suitable for follow-up after treatment of H . pylori infection in elderly patients.

Antibiot Khimioter, 1993 Jul, 38(7), 44 - 7
{Estimation of the proper use of drugs in the treatment of inpatients with acute intestinal infections}; Seleznev EF; A study was performed to reveal whether the pharmacotherapy of patients with acute intestinal infections in hospitals of 24 territories of the CIS was proper . The results showed that the use of antibacterial chemotherapeutics was everywhere excessive and the physicians thus tried to guarantee the success . The calculations revealed that the cost of the antibacterial drugs (in the prices of 1991) used improperly amounted to 1.26 rubles per an adult patient and 1.68 rubles per a child patient with reference to 1 average case . The negative aspects of such a pharmacotherapy of acute intestinal infections were the improper use in some regions of infusion dehydrating and antihistamine agents and polypragmasia . A highly variable use of bacteriophages, bacterial biological preparations, enzymes, immunostimulants and other drugs in the treatment of analogous infections in various hospitals was revealed.

Biol Pharm Bull, 1993 Jul, 16(7), 726 - 8
Inhibition of GABAA receptor-mediated current responses by enoxacin (new quinolone) and felbinac (non-steroidal anti-inflammatory drug) in Xenopus oocytes injected with mouse-brain messenger RNA; Kawakami J et al.; The convulsant interaction between enoxacin (ENX), a new quinolone antibacterial agent (NQ), and felbinac (FLB), a non-steroidal anti-inflammatory drug (NSAID), in vivo was reproduced as the change of GABA-induced current response in Xenopus oocytes injected with mouse brain mRNA . GABA (10 microM) response was inhibited by ENX in a dose-dependent manner, and IC50 of ENX was 96 microM . Moreover, the inhibitory effect of ENX was 80-fold potentiated in the presence of 10 microM FLB . The GABAA-antagonistic interaction between these two drugs in vitro was considered a possible mechanism of convulsant reaction after concomitant administration of NQs and NSAIDs in vivo.

FEBS Lett, 1993 Jun 28, 325(1-2), 63 - 6
The humoral antibacterial response of Drosophila; Hoffmann JA et al.; Drosophila, like other insects, responds to the injection of bacteria by the rapid and transient synthesis of a battery of potent antibacterial peptides . Only a few of these peptides have been fully characterized to date . We review our recent data on the control of the expression of a gene encoding one of the induced peptides, i.e . diptericin . Our data highlight the role of proximal cis-regulatory motifs similar to regulatory elements binding NF-kappa B and NF-IL6 in promoters of some immune genes of mammals . We argue that the Drosophila host defense is homologous to the mammalian acute phase response.

Obstet Gynecol, 1993 Jun, 81(6), 922 - 5
Preoperative skin preparation and intraoperative pelvic irrigation: impact on post-cesarean endometritis and wound infection; Magann EF et al.; OBJECTIVE: To determine the impact of two skin preparation methods and two techniques of pelvic irrigation on the incidence of post-cesarean endometritis and wound infection in an indigent patient population . METHODS: A randomized study was performed in 100 cesarean patients . Subjects were assigned to one of four groups, involving either standard skin preparation (povidone-iodine {7.5%} scrub followed by povidone-iodine {10%} solution) or special skin preparation (5-minute scrub with parachlorometaxylenol followed by povidone scrub and solution), and either normal saline or antibiotic (cefazolin sodium, 1 g in 500 mL normal saline) irrigation of the pelvis and subcutaneous tissue at uterine and fascial closure . Four groups of patients were formed: standard skin preparation plus normal saline irrigation, standard preparation plus antibiotic irrigation, special preparation plus normal saline irrigation, and special preparation plus antibiotic irrigation . RESULTS: Endometritis occurred significantly more often in the combined groups that did not include antibiotic irrigation than in the combined groups involving antibiotic irrigation (P < .001) . In contrast, comparison of skin preparation methods between povidone-iodine alone versus preparation including parachlorometaxylenol indicated no significant difference (P = .22) . CONCLUSION: Skin preparation with an antibacterial scrub in addition to standard povidone-iodine scrub and solution does not appear to play as significant a role in the reduction of post-cesarean endometritis or wound infection as does intraoperative pelvic irrigation with antibiotic solution.

Cell Mol Biol (Noisy-le-grand), 1993 Jun, 39(4), 383 - 7
Interaction of neomycin with human erythrocytes; Di Massimo C et al.; This study has been undertaken to verify if neomycin, known to be toxic because it interacts with membrane-bound phosphatidylinositol-4,5-biphosphate, may lead to an extensive perturbation of the membrane organization of human erythrocytes . By comparison, the effects induced by a non toxic aminocyclitol antibacterial agent as spectinomycin were examined . Our data exclude extended alterations of the membrane and hence large structural changes of the whole cell for both the drugs probably as a consequence of the extreme difficulty of penetration because of their selective hydrophilic features . However, only neomycin seems to present a binding on negatively charged regions of erythrocyte membranes, that could be responsible of its remarkable toxicity.

Antimicrob Agents Chemother, 1993 Jun, 37(6), 1285 - 8
Susceptibility of Mycobacterium malmoense to antibacterial drugs and drug combinations; Hoffner SE et al.; Mycobacterium malmoense is an opportunistic pathogen with increasingly recognized clinical importance . It is mainly isolated in northern Europe and Great Britain, most often from patients with pulmonary infections . Conventional therapy of M . malmoense infections with antituberculosis drugs is often of limited value, and there is thus a need for improved drug regimens . The potential efficacies of new alternative drugs, such as quinolones, macrolides, amikacin, and rifabutin, are still unknown, and so is the pathogen's in vitro susceptibility to most of these drugs . In this study, we used the BACTEC system for determining the pattern of resistance of clinical M . malmoense isolates to a number of antibacterial drugs as well as their possible synergistic interactions when each of them was combined with ethambutol . The majority of the strains were resistant or moderately resistant to the drug when it was tested alone at selected concentrations . However, pronounced in vitro synergism was demonstrated for combinations of ethambutol with ciprofloxacin, amikacin, and rifampin, rendering most isolates susceptible to the combined drugs . Thus, for in vitro susceptibility testing of M . malmoense, examination of the possible synergistic effects of combined drugs also can be recommended.

Farmaco, 1993 Jun, 48(6), 777 - 93
Synthesis, antibacterial and antifungal activity of metal (II) complexes of 2-acetylpyridine thiosemicarbazones; Offiong OE et al.; 2-Acetylpyridine-(4-methylthiosemicarbazone), 2-acetylpyridine-(2- methylthiosemicarbazone) and their metal (II) complexes have been synthesized and characterized by chemical and spectral methods . They were studied for their antibacterial, antifungal and amoebicidal activity in vitro and for their toxicity in vivo . The ligands and their metal (II) complexes exhibited significant activity against a wide spectrum of microorganisms . The metal (II) complexes derived from 2-acetylpyridine-(4-methylthiosemicarbazone) seem to be the most active compounds.

Tuber Lung Dis, 1993 Jun, 74(3), 187 - 90
The role of bacterial super infection in extensive pulmonary tuberculosis . Data from protected brush cultures in untreated patients from the University of South Alabama Medical Center, Mobile, Alabama, USA; Middleton R 3rd et al.; Pulmonary tuberculosis (TB) and bacterial pneumonia are both characterized by fever, cough, and purulent sputum production . Although TB alone can cause these symptoms, the possibility of a concomitant bacterial pneumonia has led some clinicians to treat these patients empirically with antibacterial agents . Neither the benefit of such empiric antibiotic therapy nor transtracheal aspirate cultures from patients with pulmonary TB have yielded consistent results . Consequently, we performed a prospective study to obtain lower airway secretions via a bronchoscopic protected specimen brush (PSB) technique for quantitative aerobic and anaerobic cultures from untreated patients with extensive pulmonary TB (defined as cavitary disease or involvement of > or = 3 segments) . We obtained bronchoscopic samples from 3 untreated men aged 21, 61, and 60 years with extensive pulmonary TB . There was no significant bacterial growth (aerobic or anaerobic) from the specimens obtained . These results, therefore, do not support the hypothesis that bacterial pneumonia is a common concomitant of extensive pulmonary TB.

Mol Microbiol, 1993 Jun, 8(6), 1025 - 30
Physical organization of lipids in the cell wall of Mycobacterium chelonae; Nikaido H et al.; Mycobacterial cell wall functions as an effective permeability barrier, making these bacteria resistant to most antibacterial agents . It has been assumed that this low permeability was due to the presence of a large amount of unusual lipids in the cell wall, but it was not known how these lipids are able to produce such an exceptional barrier . We report here the first experimental evidence on the physical arrangement of these lipids based on X-ray diffraction studies of purified Mycobacterium chelonae cell wall, a result suggesting that the hydrocarbon chains of the cell-wall lipids are arranged predominantly in a direction perpendicular to the cell wall surface, probably producing an asymmetric bilayer structure.

Jpn J Antibiot, 1993 Jun, 46(6), 486 - 91
{An evaluation of a therapy with antibacterial and antifungal agents infections with hematological disorders}; Inoue N et al.; The primary objective of this study is to confirm the efficacy and safety of combination therapy with antibacterial and antifungal drugs for patients with hematological disorders complicated with infections of unknown causative organisms . The subjects consisted of 55 patients with hematological disorders, 28 males and 27 females, ranging from 1 to 78 years of age, with an average age of 34 years . The breakdown of the patients by disease was: 41 leukemias, 10 malignant lymphomas, 3 myelodysplastic syndromes and an aplastic anemia . All patients were treated with sulbactam/cefoperazone (SBT/CPZ) and aminoglycoside (AG) plus fluconazole (FLCZ) as an empiric therapy . Overall efficacy rate was 54.5% for all the patients: 57.7% for patients with suspected sepsis and 0% for those with pneumonia from which unknown organisms were detected . The efficacy rate was 59.4% for patient who had been previously treated with other antibiotics and 47.8% for those who had not previously been treated . The above results suggested that this combination therapy might be effective for severe infections of unknown causative organisms associated with hematological disorders.

Jpn J Antibiot, 1993 Jun, 46(6), 437 - 43
{Usefulness of (1-->3)-beta-D-glucan measurement for diagnosis of deep mycosis}; Furuya T et al.; The number of deep mycosis has been increasing because of increases in immunocompromised hosts and in fungal colonization associated with increasing use of broad-spectrum antibacterial antibiotics . Based on these phenomenon, a simple test method for an early diagnosis of deep mycosis is urgently desired . We therefore investigated the usefulness of assaying a fungal cell component, (1-->3)-beta-D-glucan (beta-glucan) . The amount of beta-glucan was obtained from the difference between the amounts determined using Toxicolor and Endospecy, and the serum levels of more than 10 pg/ml were considered positive signs for beta-glucan . The following results were obtained: We found that beta-glucan was positive in 75% of the patients who had been definitely diagnosed to have mycosis, and in 58.3% of the patients strongly suspected of mycosis . The numbers of beta-glucan positive patients' in these 2 groups of patients were significantly different from that in those without mycosis (14.7%, P < 0.05) . Thus a usefulness of beta-glucan measurement for the diagnosis of mycosis was demonstrated . However, beta-glucan was sometimes negative even in patients with fungemia at an early phase of the disease and turned positive several days later . Even in a patient with definite lung mycosis, who had a latent circumscribed lesion (afebrile and CRP-negative), beta-glucan was also negative . From these findings, one should be aware that the beta-glucan test produces false negatives even in patients with definite mycosis and that the test should be repeated during the course of the disease.

Vet Parasitol, 1993 Jun, 48(1-4), 109 - 25
Environmental effects of the usage of avermectins in livestock; Halley BA et al.; Abamectin (avermectin B1) and ivermectin (22,23-dihydroavermectin B1) are high molecular weight hydrophobic compounds, active against a variety of animal parasites and insects . Numerous environmental fate and effects studies have been carried out in the development of these two compounds as antiparasitic agents and for abamectin as a crop protection chemical . They were found to be immobile in soil (Koc > or = 4000), rapidly photodegraded in water (degradation half-life (t1/2) in the summer 0.5 days or less) and as thin films on surfaces (t1/2 < 1 day), and aerobically degraded in soil (ivermectin in soil/feces mixtures (t1/2) = 7-14 days; avermectin B1a in soils, t1/2 = 2-8 weeks) to less bioactive compounds . Abamectin is not taken up from the soil by plants, nor is it bioconcentrated by fish (calculated steady-state bioconcentration factor of 52, with rapid depuration) . Daphnia magna is the fresh water species found to be most sensitive to ivermectin and abamectin (LC50 values of 0.025 and 0.34 ppb respectively); fish (e.g . rainbow trout) are much less sensitive to these compounds (LC50 values of 3.0 ppb and 3.2 ppb, respectively) . In the presence of sediment, toxicity toward Daphnia is significantly reduced . The metabolism and degradation of ivermectin and abamectin result in reduced toxicity to Daphnia . Abamectin and ivermectin possess no significant antibacterial and antifungal activity . They display little toxicity to earthworms (LC50 values of 315 ppm and 28 ppm in soil for ivermectin and abamectin, respectively) or avians (abamectin dietary LC50 values for bobwhite quail and mallard duck of 3102 ppm and 383 ppm, respectively), and no phytotoxicity . Residues of the avermectins in feces of livestock affect some dung-associated insects, especially their larval forms . This does not delay degradation of naturally formed cattle pats under field conditions; however, in some cases, delays have been observed with artificially formed pats . Based on usage patterns, the availability of residue-free dung and insect mobility, overall effects on dung-associated insects will be limited . As abamectin and ivermectin undergo rapid degradation in light and soil, and bind tightly to soil and sediment, they will not accumulate and will not undergo translocation in the environment, minimizing any environmental impact on non-target organisms resulting from their use.

Infect Dis Clin North Am, 1993 Jun, 7(2), 435 - 44
Antifungal susceptibility testing . Current state of technology, limitations, and standardization; Pfaller MA et al.; In parallel with the escalating incidence of serious, invasive fungal infections in the immune-compromised host has been the development and use of new, potentially efficacious antifungal agents as well as recognition of both primary and secondary resistance to such drugs by the etiologic mycotic agents . These findings have generated considerable enthusiasm for a reproducible and standardized means for the laboratory evaluation of antifungal drugs . For over a decade, global investigations have ensued in the hope of generating laboratory methods analogous to those used for antibacterial drugs that may predict the optimal therapeutic choice for clinicians treating mycoses . This article reviews the background, history, and development of in vitro antifungal susceptibility efforts, details the problems inherent in this area of laboratory medicine/infectious diseases, and assesses the contemporary aspects of standardization.

J Antibiot (Tokyo), 1993 Jun, 46(6), 992 - 1012
Synthesis and structure-activity relationships of new cephalosporins with aminoimidazoles at C-7 . Effect of the pKa of the C-7 aminoimidazole on antibacterial spectrum and beta-lactamase stability; Jung F et al.; Cephalosporins with new aminoimidazole heterocycles at C-7 have been synthesized by reaction of anti-alpha-aminooximes with C-7 dihaloisocyanocephalosporins esters or by direct condensation of 2-fluoroimidazoles with C-7 aminocephalosporins esters . These compounds combine a broad spectrum of antibacterial activity, including Gram-negative and Gram-positive organisms with a good beta-lactamase stability . Activity is discussed in terms of its relationship to the pKa of the C-7 aminoimidazole heterocycle, basic C-7 aminoimidazole residues gave cephalosporins with the best beta-lactamase stability but the poorest activity against Gram-positive organisms . An additional interesting property of the C-7 imidazolylaminocephalosporins is the oral activity present in some compounds of this series.

J Antibiot (Tokyo), 1993 Jun, 46(6), 875 - 83
A new neuritogenetic compound BU-4514N produced by Microtetraspora sp; Toda S et al.; A novel neuritogenetic compound BU-4514N was isolated from the fermentation broth of Microtetraspora sp . T689-92 . It showed significant NGF-mimic activity and antibacterial activity against Gram-positive bacteria . Structural studies revealed that BU-4514N was a new chemotype antibiotic related to lydicamycin.

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