Pharmazie, 1993 Jun, 48(6), 414 - 7 Bridged bis(4-thiazolidinones) and related compounds with antibacterial activity; Pandya D et al.; Condensation of 4,4'-diaminobiphenyl ether (1) and 4,4'-diaminobiphenyl methane (6) with various aldehydes gave diarylidenebiphenyl ethers 2a-d and diarylidenebiphenyl methanes 7a-c, respectively, which on cyclocondensation with merceptoacetic acid yielded 3,3'-{oxy-bis(4,1-phenylene)}-bis{(2-substituted phenyl)-4- thiazolidinones} 3a-d and 3,3'-{methylene-bis(4,1-phneylene)}-bis{2-substituted phenyl)-4-thiazolidinones} 8a-c . A series of 2,2'-{oxy-bis(4,1-phenylenenitrilo)}-bis{3- (substituted)-4-thiazolidinones} 5a and b and 2,2'-{methylene-bis(4,1-phnylenenitrilo)}-bis{3-(substituted)-4- thiazolidinones} 10a and b were synthesized from 4,4'-diaminobiphenyl ether (1) and 4,4'-diaminobiphenyl methane (6) via the corresponding dithiocarbamide biphenyl ethers 4a and b and dithiocarbamide biphenyl methanes 9a and b by cyclocondensation with monochloroacetic acid . The structures of compounds 2-10 are supported by elemental analysis and spectral data (IR, 1H NMR, 13C NMR) . The specific rotation of compounds 3c, 8b and 8c was measured. Hinyokika Kiyo, 1993 Jun, 39(6), 517 - 21 {Clinical study of sonography and percutaneous nephrostomy in pyonephrosis}; Ishizu K et al.; Sonography and percutaneous nephrostomy (PNS) were performed on 16 patients with pyonephrosis and the following results were obtained . Sonography revealed a dilated collecting system in all cases within which, however, neither debris nor gas was observed in any case, the pelvocaliceal system appeared hypoechoic in 2 cases and anechoic in 14 cases . From the clinical symptoms and the dilated collecting system demonstrated by sonography, pyonephrosis was diagnosed in 14 cases . The purulent fluid aspirated from the collecting system confirmed the diagnosis in all cases . The clinical condition was stabilized by PNS and antibacterial therapy in all cases . However, in 5 of the patients with pyrexia for more than 6 days before PNS, sepsis developed in 3 cases and pyrexia continued for more than 3 days after the treatment in 4 cases . The affected 11 kidneys showing recovery of renal function following PNS were all salvaged by elective surgery . These findings suggest that prompt diagnosis by needle aspiration is necessary, even in the absence of any sonographically characteristic findings, whenever pyonephrosis is suspected . Our experience suggests that PNS is a useful therapeutic procedure for pyonephrosis. Scand J Dent Res, 1993 Jun, 101(3), 130 - 2 Experiments with a toothpaste containing polydimethylsiloxan/triclosan; Rolla G et al.; Polydimethylsiloxan (silicone oil) adsorbs to solid surfaces and to teeth because of its low surface tension, forming a thin, resistant layer . Triclosan is a lipid-soluble, antibacterial substance which is added to toothpastes and mouthwashes to inhibit plaque . Triclosan can be dissolved in silicone oil, conferring an antibacterial property on the layer of silicone oil which forms on solid surfaces . The aim of the present study was to determine whether a toothpaste containing triclosan/silicone oil has any effect on established gingivitis in a test panel of 33 teenagers . This toothpaste and a placebo paste were randomly distributed to the panel, and the number of gingival bleeding points was recorded . No instruction in oral hygiene was given . The panel was then examined 4 wk later and the number of bleeding points again recorded . It was found that the reduction in bleeding points was significantly higher in the group which had used the triclosan/silicone oil paste than in the placebo group . Deposition of a lipid-soluble, antibacterial agent in a layer of silicone oil which adsorbs to the tooth surfaces because of its physical properties represents a new and promising principle in preventive dentistry. Hua Xi Yi Ke Da Xue Xue Bao, 1993 Jun, 24(2), 127 - 30 {Rat bladder ubiquitin-like molecule: isolation, purification and N-terminal sequencing}; Wang B et al.; A Ubiquitin-like peptide was accidentally isolated from rat bladder by using 5% acetic acid wash while we were isolating antibacterial peptides . The purified molecule was obtained by reverse phase high performance liquid chromatography . Gas phase microsequence analysis indicated the N-terminal sequences of the molecule as follows: MET-GLN-ILE-PHE-VAL-LYS-THR-LEU-THR-GLY-LYS-THR-ILE-THR-LEU- GLU-VAL-GLU-PRO-SER-ASP-THR-ILE-GLU-ASN, which is homologous to human ubiquitin . Ubiquitin plays a role in the differentiation of pre-B lymphocytes, Thus, it is suggested from the findings of this molecule and the endogenous antibacterial polypeptides in mucosa or mucosal epithelium that mucosal epithelium also might be one of immune cells or immunity-associated cells, which may secrete effector molecules directly to kill adherent microbes and produce regulating factors in mucosal immune response. Vet Microbiol, 1993 Jun, 35(3-4), 339 - 47 The role of the pharmaceutical animal health industry in post-marketing surveillance of resistance; Lens S; The pharmaceutical animal health industry must be committed to the total life cycle of products, i.e . during both the pre- and post-marketing period . Support of antibacterial agents during the postmarketing period is not restricted to maintaining a well-established distribution and promotion system . Care has to be taken continuously to maintain and/or improve the quality, safety (for user, target animal and environment) and clinical efficacy . The pharmaceutical industry contributes to this by: 1 . Introducing antibacterials in different animal species for the most effective disease condition only and by ensuring the veterinary profession is informed about relevant findings on: a . the mechanism of action; b . pharmacodynamic properties; c . pharmacokinetic properties (plasma, target tissue); d . clinical efficacy data and in vitro sensitivity data; e . valid species-specific MIC breakpoints; f . precise dose and treatment regime . 2 . Updating on a regular basis on: a . new findings on the mechanism of action (in vitro and in vivo); b . the optimal use program in the light of changes in animal husbandry, farm management and epidemiology on national and international level; c . adjustment of species-specific MIC breakpoints when necessary . 3 . Providing continuous information in collaboration with animal health laboratories about: a . clinical field surveillance for efficacy (national, international); b . in vitro sensitivity/resistance surveillance (national, international); c . use of in vitro data to support prediction of in vivo efficacy . Surveillance of resistance, in vitro, is therefore part of a package of information needed on a routine basis by the pharmaceutical industry to allow the best possible use of antibacterials and to minimize induction of resistance.(ABSTRACT TRUNCATED AT 250 WORDS) Antibiot Khimioter, 1993 Jun, 38(6), 62 - 6 {Epidemiology of drug resistance in pathogens isolated in hospitals}; Smolianskaya AZ; A 20-year observation showed that there were significant changes in the species composition and ratio of the sensitive and resistant variants of opportunistic bacteria constituting the main part of the pathogens causing infectious complications in somatic hospitals . However, the taxonomic structure of the pathogens changed slowly, perhaps due to the ever increasing role of the hospital strains in the development of the infections in the inpatients . The higher number of the resistant variants primarily depended on the rate of the drug use, as well as on the biological and physiological properties of the bacteria, the structure of the drugs, the nature of the resistance, etc . Therefore, the following up of the species composition of the pathogens for estimating the role of every taxon in the development of the infections with their particular localization and the determining of the relative number of the strains sensitive to the drugs used in the hospitals are the obligatory conditions for rational antibacterial chemotherapy. Antibiot Khimioter, 1993 Jun, 38(6), 59 - 62 {Side effects of antibacterial therapy with respect to hydrolysis and absorption of sugars in newborns}; Sheibak MP et al.; Hydrolysis and absorption of sugars in the intestine were studied in 268 newborns at the background of antibacterial therapy of pneumonia and acute respiratory infections . It was shown that penicillins and cephalosporins induced impairment of lactose and sucrose hydrolysis followed by the development of persisting dyspepsia . The antibiotics also promoted the development of the syndrome of the malabsorption of monosugars . The use of bifidumbacterin in the complex treatment promoted the elimination of the dyspeptic syndrome and improved the membrane digestion. J Med Chem, 1993 May 28, 36(11), 1580 - 96 3-Quinolinecarboxamides . A series of novel orally-active antiherpetic agents; Wentland MP et al.; A series of novel 3-quinolinecarboxamides that are structurally similar to the quinolone class of antibacterial agents possess excellent antiherpetic properties . By modifying the quinoline ring at the 1-, 2-, 3-, and 7-positions, analogues were identified that have up to 5-fold increased HSV-2 plaque-reduction potency relative to acyclovir . In a single-dose mouse model of infection, one of the most potent derivatives in vitro, 1-(4-fluorophenyl)-1,4-dihydro-4-oxo-7-(4-pyridinyl)-3-quinolinecarbo xamide (97), displayed comparable oral antiherpetic efficacy to acyclovir at 1/16 the dose; in a multiple-dose regimen, however, 97 was 2-fold less potent . In mice dosed orally with 97, sustained plasma drug levels were evident that may account for the high efficacy observed . The molecular mechanism of action of these agents is not known; however, based on in vitro studies with acyclovir resistant mutants, it is likely that the mechanism differs from that of acyclovir . In vitro plaque-reduction potency was not generally predictive of oral efficacy in mice . An X-ray crystal structure of 97 corroborated the assignment of structure and provided useful insights as to the effect of conformation on plaque-reduction potency. J Med Chem, 1993 May 14, 36(10), 1443 - 9 Application of the hypersurface iterative projection method to bicyclic pyrazolidinone antibacterial agents; Boyd DB; Bicyclic pyrazolidinones are a class of synthetic antibacterial agents in which the beta-lactam ring is replaced by a five-membered ring . These compounds possess electronic and shape properties required for inhibiting penicillin-binding proteins essential for bacterial cell growth . A novel approach called the hypersurface iterative projection (HIP) method, which is based on three-dimensional computer graphics, allows available structure-activity information to be extrapolated to new synthetic targets . By updating the data set as the SAR evolves, the computer graphics reveal regions of parameter space to explore for optimum activity and regions yet unexplored . A large substituent parameter database is used to propose appropriate substituents . For the bicyclic pyrazolidinones, lipophilicity and particularly electron-withdrawing properties of the 3-substituent are shown to correlate strongly with minimum inhibitory concentrations (MIC) . Antibacterial potency is intimately related to the activating effect of 3-substituents on chemical reactivity . The HIP method succeeded in proposing the most potent member of the series prior to synthesis and also showed when all of parameter space was reasonably well explored to the extent the chemistry allowed. Antimicrob Agents Chemother, 1993 May, 37(5), 1073 - 81 Pharmacodynamics of intravenous ciprofloxacin in seriously ill patients; Forrest A et al.; Seventy-four acutely ill patients were treated with intravenous ciprofloxacin at dosages ranging between 200 mg every 12 h and 400 mg every 8 h . A population pharmacokinetic-pharmacodynamic analysis relating drug exposure (and other factors) to infectious outcome was performed . Plasma samples were obtained and assayed for ciprofloxacin by high-performance liquid chromatography . Samples from patients were frequently cultured so that the day of bacterial eradication could be determined . The pharmacokinetic data were fitted by iterative two-stage analysis, assuming a linear two-compartment model . Logistic regression was used to model ciprofloxacin exposure (and other potential covariates) versus the probabilities of achieving clinical and microbiologic cures . The same variables were also modelled versus the time to bacterial eradication by proportional hazards regression . The independent variables considered were dose, site of infection, infecting organism and the MIC for it, percent time above the MIC, peak, peak/MIC ratio, trough, trough/MIC ratio, 24-h area under the concentration-time curve (AUC), AUC/MIC ratio (AUIC), presence of other active antibacterial agents, and patient characteristics . The most important predictor for all three measures of ciprofloxacin pharmacodynamics was the AUIC . A 24-h AUIC of 125 SIT-1.h (inverse serum inhibitory titer integrated over time) was found to be a significant breakpoint for probabilities of both clinical and microbiologic cures . At an AUIC below 125 (19 patients), the percent probabilities of clinical and microbiologic cures were 42 and 26%, respectively . At an AUIC above 125 (45 patients), the probabilities were 80% (P < 0.005) and 82% (P < 0.001), respectively . There were two significant breakpoints in the time-to-bacterial-eradication data . At an AUIC below 125 (21 patients), the median time to eradication exceeded 32 days; at an AUIC of 125 to 250 (15 patients), time to eradication was 6.6 days: and at AUIC above 250 (28 patients), the median time to eradication was 1.9 days (groups differed; P < 0.005) . These findings, when combined with pharmacokinetic data reported in the companion article, provide the rationale and tools needed for targeting the dosage of intravenous ciprofloxacin to individual patients' pharmacokinetics and their bacterial pathogens' susceptibilities . An a priori dosing algorithm (based on MIC, patient creatine clearance and weight, and the clinician-specified AUIC target) was developed . This approach was shown, retrospectively, to be more precise than current guidelines, and it can be used to achieve more rapid bacteriologic and clinical responses to ciprofloxacin, as a consequence of targeting the AUIC. J Am Acad Dermatol, 1993 May, 28(5 Pt 1), S7 - S11 Progression of interdigital infections from simplex to complex; Leyden JJ; The dynamics of symptomatic toe web infections often involve an ecologic interplay in which an initial dermatophyte infection provides a hospitable niche for subsequent colonization by bacteria . Several studies suggest that exacerbation of a mild dermatophyte infection (dermatophytosis simplex) can arise in the occlusive environment of the toe web space . Fungal infection induces damage to the stratum corneum, which allows overgrowth of resident bacteria and maceration, itching, and often malodor at the site (dermatophytosis complex) . Because fungi frequently elaborate antibacterial substances, the superinfecting bacteria generally are resistant to penicillin and other antibiotics . A flourishing bacterial superinfection may mask the underlying fungal cause, making it difficult to obtain a positive fungal culture. Ann Otol Rhinol Laryngol, 1993 May, 102(5), 385 - 95 Development of secretory elements in murine tubotympanum: lysozyme and lactoferrin immunohistochemistry; Park K et al.; Secretory activity, particularly of antibacterial agents such as lysozyme and lactoferrin, is an important aspect of the mucosal defense mechanism, and the development of these agents may have a direct bearing on the susceptibility of the ear to infection . In this study, the secretory cells of the murine tubal epithelium were first observed at gestational day 17 . Although tubal glands began to develop on gestational day 18, their secretory activity was first shown on postnatal day 3 . The number of secretory cells of the tubal epithelium increased rapidly immediately after birth, while that of the tubal glands showed a gradual increase from postnatal day 3 . The epithelial secretory cells in the tubotympanum matured at birth, but the tubal glands matured gradually after birth . Lysozyme was first recognized in the epithelial secretory cells on postnatal day 1, while lactoferrin was first detected in the tubal glands on postnatal day 3 . Both lysozyme and lactoferrin were co-localized in the serous cells of the tubal glands . The secretion of lysozyme and lactoferrin seemed to reflect the maturation of the secretory cells in the murine tubotympanum. Mol Pharmacol, 1993 May, 43(5), 795 - 800 Indomethacin/ibuprofen-like anti-inflammatory agents selectively potentiate the gamma-aminobutyric acid-antagonistic effects of several norfloxacin-like quinolone antibacterial agents on {35S}t-butylbicyclophosphorothionate binding; Squires RF et al.; Four piperazinoquinolone antibacterial drugs (norfloxacin, ciprofloxacin, enoxacin, and pipemidic acid), known to be gamma-aminobutyric acid (GABA) antagonists, fully reversed the inhibitory effect of GABA on {35S}t-butylbicyclophosphorothionate ({35S} TBPS) binding to rat brain membranes in vitro . Twelve indomethacin/ibuprofen-like arylalkanoic acid (AAA) anti-inflammatory drugs alone had no effect on {35S}TBPS binding, or on its inhibition by GABA, but potentiated the GABA-antagonistic effects of the four quinolones . Felbinac (4-biphenylacetic acid) was most potent in this respect (EC50 = 110 nM, together with 5 microM norfloxacin), followed by flurbiprofen > anirolac > metiazinic acid > tolmetin = ketoprofen = fenbufen = indomethacin > fenoprofen > ibuprofen = (+)-naproxen = sulindac . Other anti-inflammatory analgesic drugs, including aspirin, diclofenac, diflunisal, meclofenamic acid, mefenamic acid, nambumetone, phenacetin, piroxicam, and phenylbutazone, failed to potentiate the GABA-antagonistic effect of norfloxacin . Felbinac (1 microM) increased the GABA-antagonistic potencies of norfloxacin and enoxacin about 26-fold, while increasing those of ciprofloxacin and pipemidic acid 7-fold and 2.3-fold, respectively . Using subsaturating concentrations of the four quinolones, concentration-response curves for felbinac yielded EC50 values ranging from 110 nM with 5 microM norfloxacin to 1.3 microM with 100 microM pipemidic acid . Three other piperazinoquinolone antibacterial agents (amifloxacin, difloxacin, and fleroxacin) and four nonpiperazinoquinolone anti-bacterial agents (oxolinic acid, cinoxacin, nalidixic acid, and piromidic acid) were much weaker GABA antagonists and were not significantly potentiated by felbinac . All other known GABAA receptor blockers tested, including R 5135, pitrazepin, bicuculline, SR 95531, strychnine, D-tubocurarine, thebaine, securinine, theophylline, and caffeine, were not potentiated by felbinac . Our results suggest that norfloxacin and related piperazinoquinolones, acting at GABAA receptors, may induce a high affinity binding site for indomethacin/ibuprofen-like anti-inflammatory agents (the AAA site) that, when occupied, reciprocally increases the affinities of the quinolones for GABAA receptors . The AAA binding site may be a new site in the GABAA receptor complex. EMBO J, 1993 May, 12(5), 2085 - 97 Mutational analysis of a type II topoisomerase cleavage site: distinct requirements for enzyme and inhibitors; Freudenreich CH et al.; We have analyzed the DNA sequence requirements for cleavage of a 30 bp oligonucleotide that contains a strong bacteriophage T4 type II topoisomerase site . A novel method was used to generate substrates with each of the four nucleotides at 10 positions surrounding the cleavage site, and mutant substrates were also prepared for the four internal positions of the staggered cleavage site . The substrates were tested for cleavage in the presence of several inhibitors that induce enzyme-mediated cleavage: four antitumor agents of different classes (an aminoacridine, a substituted anthraquinone, an ellipticine derivative and an epipodophyllotoxin) and one antibacterial quinolone . At eight nucleotide positions flanking the cleavage site, the same preferred bases were found regardless of which inhibitor was present . These preferred bases show dyad symmetry with respect to the cleavage site, indicating that both protomers of the topoisomerase homodimer interact with DNA in an analogous manner . In addition, we found that the preferred bases on the 5' side of each cleaved phosphodiester bond are highly specific to the inhibitor used in the cleavage reaction . These results strongly suggest that the inhibitors interact directly with the DNA bases at the cleavage site, placing the inhibitor binding site precisely at the site of DNA cleavage. Acta Pharm Hung, 1993 May, 63(3), 105 - 14 {Correlation between the structures and physicochemical properties of chemotherapeutic fluoroquinolone agents}; Szasz G et al.; The acid-base properties, the lipophilicity and the HPLC behaviour of nine antibacterial fluoroquinolone derivatives were studied to reveal relationship between these physico-chemical parameters and the chemical structure . Basicity of compounds with two proton-binding sites is depicted here in terms of protonation macro- and microconstants . The concentrations of microspecies (cation, zwitterion, neutral and anion) were calculated in the function of pH . The microspeciation of fluoroquinolones were used to derive relationship between the apparent and true octanol/water partition coefficients . An analysis of structure-chromatographic behaviour has been performed utilizing the retention values was determined in a chromatographic system methanol-aqueous phosphate buffer/ODS . Close correlation was found between the lipophilicity and chromatographic behaviour of the tested compounds when pH dependence and the influence of an ionpairing agent were investigated. Ann Pharmacother, 1993 May, 27(5), 594 - 8 Vancomycin therapeutic drug monitoring: is it necessary? Freeman CD, Quintiliani R, Nightingale CH. OBJECTIVE: To review the literature and assess the validity of obtaining vancomycin serum drug concentrations in patients . DATA SOURCES: A MEDLINE search of the English literature and a bibliographic review of articles pertaining to vancomycin serum concentrations, their use, and the rationale of cited therapeutic ranges . STUDY SELECTION AND DATA EXTRACTION: Studies pertaining to the use of vancomycin concentrations in the clinical setting, methods for predicting these concentrations, and studies that reported efficacy or toxicity associated with vancomycin use and possible correlation of serum concentrations . DATA SYNTHESIS: The usefulness of vancomycin serum concentrations, the determination of a therapeutic range of values, and their correlation to antibacterial efficacy and drug toxicity in the clinical setting are controversial . Old reports of toxicities need to be critically examined due to lack of information and the actual frequency of toxic reactions . The efficacy of vancomycin's antibacterial effect and its correlation with reported therapeutic ranges may advocate obtaining a vancomycin trough concentration in certain groups of patients . CONCLUSIONS: Determination of serum vancomycin concentrations in the clinical setting and their usefulness in patient care is questionable and unnecessary in the majority of patients. Zentralbl Veterinarmed A, 1993 May, 40(4), 241 - 8 Induction of serotonin-S2 receptor blockade during early or late stage of acute respiratory distress syndrome in double-muscled calves: a comparative study; Genicot B et al.; Ninety-four Belgian White and Blue double-muscled calves were involved in this study which aimed to compare the efficacy of a serotonin-S2 receptor blockade at two different stages of an acute respiratory distress syndrome (ARDS), i.e . at the occurrence of first clinical signs or when another anti-inflammatory compound was clinically shown to be ineffective . Metrenperone, a 5-hydroxytryptamine (5-HT2) blocker, was injected (intramuscularly, 5 times, at 12 hourly intervals, dose rate: 0.1 mg/kg) to (1) 58 calves referred to our laboratory after a treatment (group I) which lasted from 3 to 5 days and which did not improve the clinical status of the animals and (2) 36 calves investigated as soon as first clinical signs occurred (group II) . Following the severity of the ARDS, the animals from group I needed to be classified into 2 groups: group IA (moderate ARDS - n = 45) and group IB (severe ARDS - n = 13) . For animals in group I, the antibacterial compound previously used was maintained and administered during 4 more days whilst the previous anti-inflammatory drug was suppressed and replaced by metrenperone administered as mentioned above . In group II, each animal was treated with ceftiofur sodium as an antibacterial agent . A clinical score and a breathing score were calculated at each step of the investigation period, i.e . before (T0) and 1 hour (T1) after the first treatment, during the interval 12H-48H (T2) which followed this treatment and 168 H (T3) after this treatment . Four clinical parameters were also taken into account separately: rectal and cutaneous temperatures, respiratory and heart rates.(ABSTRACT TRUNCATED AT 250 WORDS) Trends Genet, 1993 May, 9(5), 178 - 83 Immune reactions in Drosophila and other insects: a model for innate immunity; Hultmark D; All insects defend themselves against bacteria and parasites, using cellular and humoral systems that are rapidly activated in infected animals . Among the induced effector molecules are antibacterial proteins and peptides such as cecropins, attacins, lysozymes and insect defensins, the genes for many of which have now been cloned . The induction of this system, which lacks clonally selected receptors like those of vertebrate B and T cells, may provide a model for innate immune reactions in other animals, including vertebrates. Res Vet Sci, 1993 May, 54(3), 372 - 8 Baquiloprim, a new antifolate antibacterial: in vitro activity and pharmacokinetic properties in cattle; White G et al.; During examination of the half-lives in cattle of a series of 5-substituted diaminobenzyl-pyrimidines, it was found that replacement of the phenyl ring of trimethoprim (TMP) by bicyclic structures, particularly a quinolyl group, led to increases in half-life . The presence of a dimethylamino group on the quinolyl ring of the compound baquiloprim (BQP) conferred a half-life of about 10 hours . In contrast to TMP (half-life about one hour), BQP was well absorbed from the gastrointestinal tract in all ages of cattle, plasma concentrations reaching a plateau on the day after dosing followed by a slow decline . BQP showed the same high broad spectrum antibacterial activity as TMP, with marked synergy with sulphonamides . Its differential binding of the dihydrofolate reductases of Escherichia coli and rat liver predicted a margin of safety similar to that of TMP . The results of efficacy studies in mice in comparison with TMP showed that the longer half-life of BQP was associated with greater efficacy, and therapeutic properties superior to those of TMP in cattle were therefore predicted for BQP. Arerugi, 1993 May, 42(5), 656 - 64 {Studies on the pathogenic mechanism of hypersensitivity to antibacterial agents--correlations of leucocyte migration activating factor and leucocyte migration inhibitory factor with interleukin-2 and interferon-gamma}; Uno K; Analyses of leucocyte migration activating factor (LMAF) and leucocyte migration inhibitory factor (LMIF), and measurements of interleukin-2 (IL-2) and interferon-gamma (IFN gamma) were performed after stimulation of suspected agents in 25 patients thought to be hypersensitive to antibacterial agents in order to clarify the pathogenic mechanism . The leucocyte migration inhibition test (LMIT) was negative in 6 patients . LMAF was detected in 11 patients and LMIF in 8 patients . IL-2 values (M +/- SE) were 6.23 +/- 1.33 BRPM u/ml in the LMIT-negative group, 17.67 +/- 1.68 BRPM u/ml in the LMAF-positive group and 7.98 +/- 0.26 BRPM u/ml in the LMIF-positive group . The LMAF-positive group was found to have a significantly higher level of production of IL-2 (p < 0.005) than the other groups . Moreover, mathematical analysis revealed a positive correlation between the leucocyte migration indices and IL-2 in the LMAF-positive group (r = 0.75, p < 0.01) . IFN gamma was detected in only 3 patients (16% of the LMIT-positive patients), i.e., in 2 patients in the LMAF-positive group and one patient in the LMIF-positive group . The patient in the LMIF-positive group was found to have lower IFN gamma values than the patients in the LMAF-positive group . Moreover, examination of the effects of IL-2 and IFN gamma on leucocyte migration revealed that IL-2 or IFN gamma and LMAF or LMIF were not exactly the same.(ABSTRACT TRUNCATED AT 250 WORDS) Acta Gastroenterol Belg, 1993 May-Aug, 56(3-4), 257 - 60 Agonist effect of erythromycin and its analogues on motilin receptors . A new family of prokinetics? Clinical interest; Peeters TL; It has been known since long that erythromycin may cause unpleasant gastro-intestinal side-effects such as nausea and vomiting . Recent studies however show that at low doses erythromycin may have a beneficial effect . Erythromycin induces the migrating motor complex in the fasted state and after a meal it accelerates gastric emptying . Although largely preliminary, its effects on esophageal, small intestinal, colonic and biliary tract motility have now been studied in several pathological conditions . Erythromycin is certainly a powerful gastrokinetic . Its antibiotic properties are a disadvantage, but more powerful derivatives devoid of antibacterial properties may soon become available . They form a new family of prokinetics. Zhonghua Yi Xue Za Zhi, 1993 May, 73(5), 289 - 91, 320 {Effects of anisodamine and ampicillin on cerebrospinal fluid in experimental E coli meningitis}; Liu YX; 24 hr and 27 hr after K1-positive E coli suspended in 0.25 ml of saline (E coli 8 x 10(7)/ml) was injected into the cisterna magna of Chinese rabbits, the levels of bacterial titer, endotoxin, malondialdehyde (MDA), lactate and lactic dehydrogenase (LDH) of the cerebrospinal fluid (CSF) were increased significantly . After ampicillin therapy alone for 3 hr, the level of CSF bacterial titer was decreased and that of LDH increased, but the others didn't change significantly . After anisodamine and ampicillin therapy for 3 hr, the levels of CSF endotoxin and lactate concentrations were decreased from 3.2 +/- 0.6 to 2.1 +/- 0.9 log 10 IU/ml and from 8.6 +/- 2.0 to 6.5 +/- 1.8 mmol/L respectively . The CSF MDA concentration (0.31 +/- 0.07) was lower than that of the nontreatment group (0.59 +/- 0.25) or the ampicillin treatment group (0.59 +/- 0.21 nmol/ml) (P < 0.01 or 0.05) . These results suggest that anisodamine combined with antibacterial therapy for experimental E coli meningitis is superior to antibacterial treatment in efficacy. Grud Serdechnososudistaia Khir, 1993 May-Jun, (3), 42 - 5 {The use of an antibacterial adhesive agent for the provision of an airtight seal and obliteration of the pleural cavity in spontaneous pneumothorax}; Vishnevskii AA et al.; The authors described a procedure for pleurodesis with a new plasma antibacterial glue in the surgical treatment of bullous lung disease complicated with spontaneous pneumothorax . A total of 28 patients were operated on . In 17 cases the glue was used for pleurodesis . The follow-up period was up to 1.5 years . No relapses of spontaneous pneumothorax were observed . No complications due to glue use were noted . Pleurodesis was evidenced by chest sonography from the absence of visceral pleural motion against parietal one. Lik Sprava, 1993 May-Jun, (5-6), 58 - 61 {The principles of administering drug and non-drug treatment methods in peptic ulcer}; Perederii VG et al.; As the result of the study optimal schemes of the ulcer disease treatment were elaborated . They include microwave resonance therapy, immunomodulatory and antibacterial drugs with regard to localisation, depth and size of the ulcerous lesion, exacerbation rate, degree of secondary immune disorders and seeding of gastric mucosa with Helicobacter pylori . The treatment suggested allows to shorten the terms of ulcer cicatrization, reduces exacerbation rate and ensures clinico-endoscopic remission in most patients with ulcer disease. Lik Sprava, 1993 May-Jun, (5-6), 137 - 40 {The efficacy of the combined antibacterial treatment of patients with colonic cancer complicated by perifocal inflammation}; Nazarov LU et al.; In patients with colonic cancer complicated by inflammation since 1989 we have been using irrigations of tumor area with antibacterial drugs (dioxidin, betadin) side by side with conventional antibacterial and detoxicating therapy . The complex antibacterial therapy having been applied in 47 patients eliminated clinical manifestation of inflammatory process . Histological and morphometrical biopsy of tumor tissue and surrounding mucosa gives a reason to conclude that the complex therapy has proved to be effective. Zh Mikrobiol Epidemiol Immunobiol, 1993 May-Jun, (3), 21 - 6 {The characteristics of the biological properties of capsule-free variants of Francisella tularensis}; Pavlovich NV et al.; Comparative study of the properties of initial capsular (cap+) and non-capsular (cap-) F . tularensis strains has revealed that the non-capsular variants have their specific biological features . The characteristic features of these variants are avirulence and inability to produce an immunogenic effect in sensitive laboratory animals . Cap- mutants, depending on the method of their obtaining, may exhibit different sensitivity to some antibacterial preparations . In contrast to the initial virulent strains, cap- variants are intensively phagocytosed by peritoneal macrophages of white mice and capable of multiplication and survival in these macrophages . F . tularensis non-capsular forms are characterized by higher superoxide-dismutase and neuraminidase activity than the initial strains, which may be the explanation of the phenomenon of their intracellular survival . At the same time the main biochemical signs of cap- strains (citrullinureidase, phosphatase and penicillinidase) remain unchanged, which determines the possibility of their classification with this subspecies. Contracept Fertil Sex, 1993 May, 21(5), 380 - 1 {Seminal fluid, bacteria, and spermatozoa }; Robillard I et al.; The antibacterial function of the seminal plasma is subdivided in: inhibition of the bacterial proliferation; inhibition of the bacterial adherence; reduction of the concentration of coiled tail spermatozoas . The reduction of the antibacterial activity of the seminal plasma can explain the high frequency of the genital tract reinfection. J Med Chem, 1993 Apr 30, 36(9), 1203 - 9 Structure-function studies of amphiphilic antibacterial peptides; Bessalle R et al.; The synthesis of 11 peptides, ranging in composition from 9 to 17 amino acid residues, by solid-phase methodology was accomplished with the purpose of studying how the amphiphilic and hydrophobic character, the size of the molecule, and the charge distribution modulate the antibacterial activity . It was found that peptides composed of 16 and 17 amino acid residues, with high hydrophobic (mainly due to Trp or Phe) and hydrophilic (due to Lys) character distributed along opposite amphiphilic faces, showed considerable antibacterial activity against clinically isolated bacteria together with Gram positive and Gram negative ATCC bacterial strains . However, the hemolytic capacity of the peptides was also significant . Decreasing the hydrophobic character of the molecule by replacing Trp or Phe with Leu residues while maintaining the basic contribution of Lys drastically reduced the hemolytic activity and only slightly decreased the bioactivity . Peptides composed of 9-10 amino acid residues with high hydrophobic and basic nature possess antibacterial activity but, in general, are less active than the larger counterpart peptides . By replacing all Trp residues of a short peptide by Leu residues, the activity was considerably reduced . Circular dichroism studies and antibacterial assays showed that shorter peptides with very low helical content, and thus deprived of amphiphilic character, still have appreciable bioactivity . This observation, coupled with the fact that due to their small size they cannot span the bacterial outer lipid bilayer, may suggest different mechanisms of action for long-chain vis-a-vis short-chain peptides. J Med Chem, 1993 Apr 16, 36(8), 1007 - 16 Mechanistic interpretation of the genotoxicity of nitrofurans (antibacterial agents) using quantitative structure-activity relationships and comparative molecular field analysis; Debnath AK et al.; Quantitative structure-activity relationship (QSAR) and comparative molecular field analysis (CoMFA) have been applied to elucidate the mechanisms of genotoxicity (SOSIP) of nitrofuran derivatives on Escherichia coli PQ37 . The following equation was developed: log SOSIP = -33.1qc2 + 1.00 log P - 1.50Isat - 1.19MR - 0.76I5,6 - 3.76; n = 40, r = 0.900, s = 0.475 . The QSAR model clearly reveals three important factors, namely, electronic (qc2), hydrophobic (log P) and steric (MR, Isat, I5,6) contributing toward the genotoxic activity of this class of compounds . qc2, the charge on the c2 atom attached to the NO2 group, supports a furan ring opening mechanism in explaining the genotoxicity . The finding of the coefficient of 1 with log P conforms to our previous findings with several different classes of mutagens acting on different systems . CoMFA analysis clearly demonstrates its potential in unraveling the steric features of the molecules through contour maps . The CoMFA cross-validated model also supports the importance of the electronic factor . It could not reveal any hydrophobic influence because the interaction energies of the CH3 and H2O probes are collinear . QSAR (classical) and CoMFA, if used judiciously, may complement each other and enhance the applicability of SAR in drug design. Biochim Biophys Acta, 1993 Apr 8, 1147(1), 132 - 6 Bactericidal catechins damage the lipid bilayer; Ikigai H et al.; The mode of antibacterial action of, the green tea (Camellia sinensis) extracts, (-)-epigallocatechin gallate (EGCg) and (-)-epicatechin (EC) was investigated . Strong bactericidal EGCg caused leakage of 5,6-carboxyfluorescein from phosphatidylcholine liposomes (PC), but EC with very weak bactericidal activity caused little damage to the membrane . Phosphatidylserine and dicetyl phosphate partially protected the membrane from EGCg-mediated damage when reconstituted into the liposome membrane with PC . EGCg, but not EC, caused strong aggregation and NPN-fluorescence quenching of PC-liposomes and these actions were markedly lowered in the presence of negatively charged lipids . These results show that bactericidal catechins primarily act on and damage bacterial membranes . The observation that Gram-negative bacteria are more resistant to bactericidal catechins than Gram-positive bacteria can be explained to some extent by the presence of negatively charged lipopolysaccharide. J Med Chem, 1993 Apr 2, 36(7), 801 - 10 7-Azetidinylquinolones as antibacterial agents . Synthesis and structure-activity relationships; Frigola J et al.; A series of novel antibacterial quinolones and naphthyridones has been prepared which contain 7-azetidinyl substituents in place of the usual piperazine or aminopyrrolidine groups . These azetidinyl derivatives were evaluated for in vitro activity by determining minimum inhibitory concentrations against a variety of bacteria . In vivo efficacy in the mouse infection model and blood levels in the mouse were determined for several compounds . The influence on the structure-activity relationships of varying substituents in the azetidine ring and at position 8 (CH, CF, CCl, N) and N-1 (ethyl, fluoroethyl, cyclopropyl, tert-butyl, 4-fluorophenyl, and 2,4-difluorophenyl) was also studied . Compounds with outstandingly broad-spectrum activity, particularly against Gram-positive organisms, improved in vivo efficacy, and high blood levels were identified in this work . 7-Azetidinyl-8-chloroquinolones were considered as warranting further development. J Chemother, 1993 Apr, 5(2), 119 - 23 Chemoprophylaxis of bacterial infections in granulocytopenic patients with ciprofloxacin vs ciprofloxacin plus amoxicillin; Fanci R et al.; Ciprofloxacin was compared to ciprofloxacin plus amoxicillin as antibacterial prophylaxis in 53 evaluable patients with neutropenic episodes, because an oral penicillin may help to decrease the incidence of gram-positive infections . The two groups were randomized and evaluated in a number of febrile episodes, in days at fever/at risk, in mean interval of first febrile episode, in duration of antibiotic therapy and in causative organisms in febrile episodes . In conclusion, no significant difference was observed between the two groups in prevention of gram-positive bacteremias. Chem Pharm Bull (Tokyo), 1993 Apr, 41(4), 758 - 62 Orally active cephalosporins . IV . Synthesis, antibacterial activity and oral absorption of 3-(1H-1,2,3-triazol-4-yl)thiomethylthio-cephalosporins; Kume M et al.; The synthesis, antibacterial activity and oral absorption of 3-(1H-1,2,3-triazol-4-yl)thiomethylthio-3-cephem-4-carboxyli c acids with various C-7 side chains (2) are described . The (1H-1,2,3-triazol-4-yl)thiomethylthio C-3 side chain was found to be an effective substituent for good oral absorption of cephalosporins with some C-7 side chains. Antimicrob Agents Chemother, 1993 Apr, 37(4), 914 - 7 Kill kinetics and regrowth patterns of Escherichia coli exposed to gentamicin concentration-time profiles simulating in vivo bolus and infusion dosing; Bastone EB et al.; The relative influence of peak concentration (Cmax) versus the area under the antibiotic concentration-time curve (AUC) on the bactericidal effect of gentamicin against Escherichia coli NCTC 10418 was studied . Bacteria in the lag phase were exposed to an in vitro gentamicin concentration series which mirrored the concentrations determined in patients after 80-mg intravenous bolus (1 min) and 80-mg intravenous infusion (30 min) doses . Bacterial viable cell counts and gentamicin concentrations were measured before and during antibiotic exposure . Both the Cmax and AUC were shown to be factors determining antibacterial activity; however, the Cmax was an independent determinant of effect . These findings indicate that bolus intravenous dosing with gentamicin could maximize bactericidal activity . Increased efficacy could result at any given daily antibiotic dose if delivered via bolus with long intervals (12 to 24 h) between doses if appropriate precautions to avoid toxicity are taken. J Leukoc Biol, 1993 Apr, 53(4), 399 - 403 Diminished transcription of interleukin-8 by monocytes from preterm neonates; Schibler KR et al.; Developmental delays, which impair antibacterial host defense, are present in the neutrophil system of human preterm neonates . We hypothesized that diminished production of interleukin-8 (IL-8), a neutrophil chemotactic peptide, might in part be responsible for these defects . To test this, monocytes from the blood of preterm neonates, term neonates, and adults were isolated immunologically by "negative panning" and subsequently stimulated with interleukin-1 alpha (IL-1 alpha), tumor necrosis factor alpha (TNF-alpha), or lipopolysaccharide (LPS), after which IL-8 levels in the supernatants were measured by ELISA . Total cellular RNA was extracted and IL-8 mRNA was assessed by Northern blotting and by competitive polymerase chain reaction (PCR) analyses . After stimulation with IL-1 alpha, IL-8 accumulation was lowest in supernatants of monocytes from preterm neonates, intermediate in supernatants of monocytes from term neonates and greatest from monocytes of adults . Similarly, when stimulated with TNF-alpha or LPS, monocytes from preterm neonates produced less IL-8 than cells from term neonates and adults . These differences in IL-8 concentrations paralleled differences in IL-8 mRNA expression. J Clin Periodontol, 1993 Apr, 20(4), 238 - 43 The effects of Acacia arabica gum on the in vitro growth and protease activities of periodontopathic bacteria; Clark DT et al.; The antibacterial activity of acacia gum was assessed using fresh isolates and reference strains of Actinobacillus actinomycetemcomitans, Capnocytophaga spp., Porphyromonas gingivalis, Prevotella intermedia and Treponema denticola . A fine aqueous suspension of gum was produced by sonication and then a soluble fraction isolated by centrifugation and membrane filtration . These preparations were incorporated into columbia agar at doubling concentrations . Growth of P . gingivalis and P . intermedia cultures on the agar was inhibited by whole gum sonicate at concentrations of 0.5-1.0% w/v . Both species showed reduced susceptibility when horse blood was present in the agar . The gum soluble fraction did not inhibit growth of any bacterial culture . The effect of acacia on bacterial proteases was examined with cell sonicates from log phase broth cultures . Enzyme activities were determined by fluorimetric assay with various synthetic peptide substrates . Most protease activities reduced in the presence of 0.5% w/v gum sonicate, with the trypsin-like activities of P . gingivalis and P . intermedia proving most sensitive . The gum soluble fraction was nearly always less inhibitory than the sonicate . The action of acacia gum against suspected periodontal pathogens and their enzymes suggests that it may be of clinical value. Biochem J, 1993 Apr 1, 291 ( Pt 1), 275 - 9 Purification, sequence and antibacterial activity of two novel sapecin homologues from Sarcophaga embryonic cells: similarity of sapecin B to charybdotoxin; Yamada K et al.; Two sapecin homologues were purified from the culture medium of NIH-Sape-4, an embryonic cell line of Sarcophaga peregrina (flesh fly) . These homologues contained six cysteine residues with exactly the same disulphide pairings as those in sapecin . The amino acid sequence of one of them, sapecin C, was also very similar to that of sapecin . The other homologue, sapecin B, was less similar to sapecin but showed significant similarity to charybdotoxin, an inhibitor of K+ channels isolated from a scorpion venom . Like sapecin, these homologues repressed the growth of various Gram-positive bacteria. Am J Gastroenterol, 1993 Apr, 88(4), 510 - 3 Esophagitis and Helicobacter pylori in children: incidence and therapeutic implications; Rosioru C et al.; The relationship between gastric Helicobacter pylori colonization and esophagitis was determined in 457 children undergoing endoscopic evaluation of abdominal pain and/or vomiting . In all patients, biopsies of the esophagus were examined histologically, and two antral biopsies were analyzed for the presence of H . pylori, using standard microbiological and histochemical techniques . The incidence of biopsy-proven esophagitis was similar in H . pylori-positive (15/56 patients) and -negative (94/401; p = NS) groups . Clinical improvement, after 2 months of antisecretory therapy with H2-receptor antagonists, was independent of H . pylori status (11/15 vs . 68/94 responders; p = NS) . All 26 H . pylori-negative nonresponders became asymptomatic with a second course of H2-blockers . The 4/15 H . pylori-positive patients (all of whom had associated gastritis/duodenitis) who failed antisecretory therapy responded clinically to treatment with amoxicillin plus bismuth subsalicylate . These data indicate that primary treatment of biopsy-confirmed esophagitis in children should include anti-secretory agents, regardless of H . pylori status . A small percentage of H . pylori-positive patients with esophagitis and concomitant gastroduodenal inflammation may require additional antibacterial therapy, suggesting that presence of the organism should be assessed in all pediatric patients undergoing upper endoscopic evaluation. EMBO J, 1993 Apr, 12(4), 1569 - 78 Apidaecin multipeptide precursor structure: a putative mechanism for amplification of the insect antibacterial response; Casteels-Josson K et al.; Apidaecins are the most prominent components of the honeybee humoral defense against microbial invasion . Our analysis of cDNA clones indicated that up to 12 of these short peptides (2 kDa) can be generated by processing of single precursor proteins; different isoforms are hereby linked in one promolecule . Assembly of the multipeptide precursors and the putative three-step maturation are strongly reminiscent of yeast alpha-mating factor . Bioactive apidaecins are flanked by the two 'processing' sequences, EAEPEAEP (or variants) and RR; joined together, they form a single unit that is repeated numerous times . The number of such repeats is variable and was reflected in the observed diversity of transcript lengths . Each such transcript is likely to be encoded by a different gene, forming a tight gene cluster . While transcriptional activation upon bacterial challenge is not exceptionally fast, the multigene and multipeptide precursor nature of the apidaecin genetic information allows for amplification of the response, resulting in a real overproduction of peptide antibiotic . Enhanced efficiency of the 'immune' response to bacterial infection through such a mechanism is, to our knowledge, unique among insects. EMBO J, 1993 Apr, 12(4), 1561 - 8 Insect immunity . Two 17 bp repeats nesting a kappa B-related sequence confer inducibility to the diptericin gene and bind a polypeptide in bacteria-challenged Drosophila; Kappler C et al.; The Drosophila diptericin gene codes for a 9 kDa antibacterial peptide and is rapidly and transiently expressed in larvae and adults after bacterial challenge . It is also induced in a tumorous Drosophila blood cell line by the addition of lipopolysaccharide (LPS) . The promoter of this gene contains two 17 bp repeats located closely upstream of the TATA-box and harbouring a decameric kappa B-related sequence . This study reports that the replacement of the two 17 bp repeats by random sequences abolishes bacteria inducibility in transgenic fly lines . In transfected tumorous blood cells, the replacement of both or either of the 17 bp motifs reduces dramatically LPS inducibility, whereas multiple copies significantly increase the level of transcriptional activation by LPS challenge . A specific DNA-protein binding activity is evidenced in cytoplasmic and nuclear extracts of induced blood cells and fat body . It is absent in controls . It is proposed that induction of the diptericin gene mediated by the two 17 bp repeats occurs via a mechanism similar to that of mammalian NF-kappa B. Zhonghua Yi Xue Za Zhi, 1993 Apr, 73(4), 217 - 9, 253 {Comparison of acid and Helicobacter pylori in ulcerogenesis of duodenal ulcer disease}; Hu FL; To test the efficacy of short-term ranitidine and antibacterial drugs in patients with H . Pylori associated duodenal ulcer disease and to compare the importance of acid and H . Pylori in ulcerogenesis, 90 outpatients were randomly assigned to one of five regimens: ranitidine, 150 mg in the morning and at bedtime; gentamicin, 40 mg tid; terramycin, 500 mg tid; furazolidone, 100 mg tid; or berberine, 300 mg tid . The patients were evaluated endoscopically, microbiologically and histologically before and 6 weeks after oral administration of the drugs . There were no significant differences among the 5 groups with regard to age, sex, duration of disease, nonsmokers and ulcer size . The efficacy of ranitidine and antibacterial drugs was as follows: ulcer healing: ranitidine 97%; antibacterial drugs 53%-67%; H . Pylori clearance, ranitidine 3%, antibacterial drugs 40%-60%; improvement of accompanying antral gastritis, ranitidine 7%, antibacterial drugs 67%-73%; disappearance of active antral gastritis, ranitidine 7%, antibacterial drugs 50%-71% . We conclude that the healing of duodenal ulcer is not influenced by the presence of H . Pylori, and does not appear to be associated with improvement of accompanying antral gastritis and disappearance of active antral gastritis . These findings suggest that acid secretion is more important than H . Pylori in ulcerogenesis. Antimicrob Agents Chemother, 1993 Apr, 37(4), 903 - 4 Uptake of itraconazole by alveolar macrophages; Perfect JR et al.; Itraconazole is a broad-spectrum potent triazole antifungal agent . Its efficacy in treatment cannot always be explained by body fluid drug levels . In this study, itraconazole was shown to accumulate into host cells . Its intracellular accumulation in cells is greater than that of the antibacterial agent clindamycin, which is known for intracellular localization, and the uptake process does not appear to be active . This ability to reach high concentrations intracellularly may be an important property for the in vivo efficacy of itraconazole. Pediatr Infect Dis J, 1993 Apr, 12(4), 321 - 5 Rhinovirus infection associated with serious illness among pediatric patients; McMillan JA et al.; Rhinovirus is an important cause of respiratory infection among all age groups, but it is primarily thought of as being responsible for upper respiratory tract infection . Rhinovirus was isolated from the respiratory tract of 48 pediatric patients who were hospitalized (40) or seen in a pediatric emergency room (8) during the period of July, 1985, through December, 1988 . Twenty-eight (58%) of the patients presented during the spring and early summer . Forty-one (86%) of the 48 patients were less than 12 months of age . All except four of the patients had viral cultures performed because of respiratory symptoms . Bronchiolitis was the single most frequent clinical diagnosis and was noted in equal proportion among children less than 3 months and 3 to 12 months of age . Nine patients were assigned a diagnosis of suspected sepsis . Rhinovirus infection was a complication of underlying illness for 17 (44%) of the 40 hospitalized patients, and those patients tended to be older than the otherwise healthy hospitalized infants with rhinovirus . Twenty-six patients (54%) were treated with antibacterial agents, although only one patient was documented to have a concomitant bacterial infection (Chlamydia trachomatis) . Overall rhinovirus isolation during the study period represented 0.7% of all specimens submitted for viral isolation compared with 8.2% for respiratory syncytial virus . Rhinovirus infection leads to hospitalization less frequently than does respiratory syncytial virus infection, but the severity of illness and clinical presentation in young infants are similar. Immunobiology, 1993 Apr, 187(3-5), 417 - 29 The bactericidal/permeability-increasing protein (BPI), a potent element in host-defense against gram-negative bacteria and lipopolysaccharide; Elsbach P et al.; The bactericidal/permeability-increasing protein (BPI), is a ca . 55 kDa cytotoxic cationic protein of polymorphonuclear leukocytes (PMN) that is present principally in the azurophilic granules . BPI is toxic only toward Gram-negative bacteria . This target specificity is attributable to the strong attraction of BPI for the lipopolysaccharides (LPS) in the bacterial envelope . BPI also binds with high affinity (apparent Kd 2-5 nM) to a broad range of LPS species and potently inhibits the biologic activities of LPS in vitro . A proteolytically prepared or recombinant ca 25 kDa N-terminal fragment of BPI carries all the antibacterial activities of holo-BPI and is more potent than the holo-protein against more resistant bacteria with S-form LPS in their envelope . The fragment is as active as holo-BPI as an LPS-neutralizing agent in vitro and more potently inhibits cytokine induction by S-form Escherichia coli in whole blood ex vivo . Recombinant forms of both proteins protect animals against the lethal effects of administered LPS. Minerva Anestesiol, 1993 Apr, 59(4), 205 - 9 {Comparison between bacterial contamination of the circular circuit and of the non-rebreathing circle used with an antibacterial filter}; Gregorini P et al.; In order to evaluate whether the risk of bacterial contamination increased during low-flow anaesthesia without bacterial filter compared with non-rebreathing anaesthesia with a disposable bacterial filter, two groups of patient were studied . In the first group a disposable circle absorber system was changed once daily, thus it was used for several patients . In the second group a non-rebreathing system was connected to a disposable bacterial filter before each surgical procedure . Samples for microbiological examination were taken preoperatively from the oropharynx and postoperatively from three locations in the circle system and in the non-rebreathing system . No difference in rates of circuit contamination were observed between the two groups. Khirurgiia (Mosk), 1993 Apr, (4), 30 - 6 {Surgical treatment of diseases of the small intestine}; Lutsevich EV et al.; The article deals with experience in surgical treatment of 375 patients with various diseases of the small intestine, rare diseases (tuberculosis, enterolithiasis, tumors, etc.) among others . These diseases were usually manifested clinically in the late stages by ileus, peritonitis or bleeding into the gastrointestinal tract . Most patients with surgical diseases of the small intestine were subjected to operation for emergency indications . Such instrumental methods as laparoscopy, selective endoscopic radiocontrast study of the small intestine, angiography, etc . are important in the diagnosis of the diseases . The authors emphasize the high diagnostic efficacy of a special method of selective endoscopic radiocontrast study, especially in tumors of the small intestine . According to the authors, general mortality rate in diseases of the small intestine is high (13%) and is mainly due to such diseases as disorders of mesenteric blood circulation, incarceration of the intestine in a hernia, adhesive obstruction, volvulus, etc . The authors claim that mortality in diseases of the small intestine can be reduced if early diagnosis, early hospitalization, and adequate surgical interventions are ensured . Among the factors contributing to increase of the efficacy of surgical operations the authors indicate efficacy of surgical operations the authors indicate precision techniques of intestinal suture application with atraumatic suture material, the use of complex biological protection of the anastomosis including treatment with low-frequency ultrasound and subsequent application of collagenic films in which antibacterial agents are deposited, and measures for stimulating reparative regeneration.(ABSTRACT TRUNCATED AT 250 WORDS) Kitasato Arch Exp Med, 1993 Apr, 65 Suppl, 1 - 12 Lipid metabolism inhibitors of microbial origin; Tomoda H et al.; Thiotetromycin is isolated from Streptomyces sp . OM-674 discovered in the course of the screening for antibacterial antibiotics . The antibiotic was found to be a specific inhibitor of type II fatty acid synthase . In order to search acyl-CoA synthetase inhibitors, a kind of yeast, Candida lipolytica, was utilized as test organism for the primary screening . Four structurally related compounds named triacsin were isolated from Streptomyces sp . SK-1894 as a specific inhibitor of acyl-CoA synthetase I of C . lipolytica . Further biochemical studies revealed that triacsins inhibit acyl-CoA synthetases from widely different sources . The inhibition is competitive with respect to long chain fatty acids . The common N-hydroxytriazene moiety of triacsins is essential for inhibition . To discover inhibitors of mevalonate biosynthesis, Vero cells were used as test organism for the screening . A beta-lactone 1233A(F-244) isolated from Scopulariopsis sp . F-244 was demonstrated to inhibit mevalonate biosynthesis with assays using cell and enzyme systems . Further studies demonstrated that the compound inhibits 3-hydroxy-3-methylglutaryl (HMG)-CoA synthase specifically and irreversibly . The geometry of the (2R, 3R)-beta-lactone ring in the structure is essential for specific inhibition against the enzyme. Biochemistry, 1993 Mar 30, 32(12), 3124 - 30 Interaction of the 47-residue antibacterial peptide seminalplasmin and its 13-residue fragment which has antibacterial and hemolytic activities with model membranes; Sitaram N et al.; The interaction of seminalplasmin (SPLN), a 47-residue antibacterial peptide, and its 13-residue fragment (SPF), which has antibacterial and hemolytic activities, with model membranes has been investigated . The fluorescence characteristics of the single Trp residue in these peptides indicate strong binding to lipid vesicles . SPLN binds more strongly to dioleoylphosphatidylglycerol vesicles compared to dioleoylphosphatidylcholine and phosphatidylserine vesicles . Localization studies using fluorescence quenchers like NO3-, I-, and acrylamide indicate that the Trp residues in both of the peptides are located away from the head group region and are associated with the hydrophobic core . Both peptides cause release of carboxyfluorescein from zwitterionic as well as anionic vesicles . The biological activities of SPLN and SPF have been rationalized in terms of lipid-peptide interactions . It is proposed that the specificity in biological activity arises due to differences in the manner in which the peptides associate with the bacterial and red blood cell surfaces. World J Surg, 1993 Mar-Apr, 17(2), 178 - 83 Prophylaxis against sepsis in patients undergoing major surgery; Morris WT; Postoperative infection in general surgical patients is discussed according to operation types . A selection of the huge literature on each group is reviewed, and details from the author's own work and ideas are presented . By discussing these points attempts are made to determine the best regimens for a given set of clinical circumstances . There is a small literature indicating that postoperative chest infection can be prevented by some antibacterial drug regimens, and this question has been addressed; it seems that in the past it has been largely ignored . Some nonantibacterial methods of reducing postoperative infection are also briefly discussed. Jpn J Antibiot, 1993 Mar, 46(3), 251 - 8 {A combined sulbactam/cefoperazone and amikacin therapy for the treatment of infections complicated with hematological diseases}; Takashima T et al.; Eighty-six patients with infections associated with hematological disorders were treated with sulbactam/cefoperazone (SBT/CPZ) and amikacin (AMK) . Among 71 evaluable cases, 30 cases had acute non-lymphocytic leukemia, 3 acute lymphoblastic leukemia, 25 malignant lymphoma, and 7 myelodysplastic syndrome as underlying diseases . Excellent responses were obtained in 33 cases (46.5%) and good responses in 14 cases (19.7%), with an overall efficacy rate of 66.2% . The efficacy rate among cases with suspected sepsis was 72.5% . This treatment was also effective in 69.2% of cases in which neutrophil counts were less than 500/microliter through the course of administration . The eradication rate was 83.3% among 6 strains in which Gram-negative rods were detected . Side effects were minimum; skin rash in 1 case, slight elevation of APTT in 3 and slight elevation of total bilirubin in 1 . Thus, this combination antibacterial chemotherapy is an effective and safe regimen for the treatment of severe infections in patients with hematological disorders. Yakugaku Zasshi, 1993 Mar, 113(3), 237 - 42 {Synthesis and antibacterial properties of 3-O-alkyl-D-glucose derivatives}; Yago K et al.; A series of 3-O-alkyl-1,2-O-isopropylidene-alpha-D-glucofuranoses (3-7), 6-deoxy-3-O-dodecyl-6-halo-1,2-O-isopropylidene-alpha-D-glucofuranose s (9-11), and 6-deoxy-3-O-dodecyl-6-halo-D-glucopyranoses (12-14) were prepared from 1,2; 5,6-di-O-isopropyridene-alpha-D-glucofuranose and their antibacterial activities were evaluated . The compounds having C12 and C14 alkylchains at C-3 of 1,2-O-isopropylidene glucoses were the most effective in vitro antibacterial screening, of which the structure-activity relationships are also discussed. J Burn Care Rehabil, 1993 Mar-Apr, 14(2 Pt 1), 158 - 63 Five percent mafenide acetate solution in the treatment of thermal injuries; Kucan JO et al.; A 5% mafenide acetate solution was used in the treatment of 669 patients with thermal injuries . This solution was used as the initial topical antibacterial agent in the treatment of the acute burn wound in 276 patients . It was initiated during the intermediate and chronic phases of burn wound therapy in 393 patients . Acid-base derangements did not occur . Discontinuation of therapy because of the patient's pain was necessary in fewer than 1% (17 of 669) of all patients treated . The incidence of rash and pruritus was extremely low . Effective antibacterial activity was achieved . This solution appears to be an effective, safe, and versatile antibacterial agent that produces minimal side effects and is useful in all phases of burn wound management. J Antimicrob Chemother, 1993 Mar, 31(3), 331 - 43 Pharmacokinetics of quinolones with special reference to the respiratory tree; Decre D et al.; Successful treatment of respiratory tract infections with the fluoroquinolones requires knowledge about whether the prescribed antibiotic will reach the site of infection at clinically active concentrations . The difficulty in extrapolating pharmacokinetic information from animal models to man has resulted in new approaches to determine the distribution of antibiotic within the human lung . Bronchoalveolar-lavage (BAL) allows the collection of epithelial-lining-fluid, alveolar macrophages, bronchial mucosal samples and sputum, thereby permitting measurement of the cellular and extracellular concentrations of an antibiotic . All fluoroquinolones show similar patterns of penetration into the lung parenchyma, bronchial mucosa or bronchial secretions . The main differences between these agents concern antibacterial potency and the nature, frequency and severity of adverse reactions . Many respiratory infections are caused by obligate or faculative intracellular pathogens, which are likely to be eradicated by the intracellular and extracellular concentrations of quinolones achieved and is supported by models of phagocytic cell function. Insect Biochem Mol Biol, 1993 Mar, 23(2), 285 - 90 Expression and characterization of cDNAs for cecropin B, an antibacterial protein of the silkworm, Bombyx mori; Kato Y et al.; To analyze the induction mechanism of antibacterial protein gene expression, cDNAs coding for cecropin B have been cloned from the B . mori fat body cDNA library . Nucleotide sequences of two positive clones were determined and their amino acid sequences deduced . They revealed that these clones coded for the same cecropin, which is identical to purified cecropin B . However, the cDNAs contained different nucleotides at the third codon position and 5' or 3' non-coding regions . Results obtained by Northern blot analysis showed that the gene expression of B . mori cecropin B was rapidly induced by Escherichia coli and reached maximum levels 8 h after immunization . The expression of cecropin B gene occurred specifically in tissues, mainly in the fat body and hemocytes. Analyst, 1993 Mar, 118(3), 277 - 80 Organic-phase biosensors for monitoring phenol and hydrogen peroxide in pharmaceutical antibacterial products; Wang J et al.; Organic-phase biosensors open new opportunities for assays of challenging pharmaceutical products . Such opportunities are illustrated for the rapid determination of phenol and peroxide antiseptics in different anti-infective formulations . The tyrosinase and peroxidase enzyme electrodes offer reliable quantification of these antibacterial agents following sample dissolution in the organic solvent . The dynamic properties of these enzyme electrodes are exploited for rapid and reproducible flow-injection assays of the pharmaceutical products (relative standard deviation = 1.6-1.9%) . Such developments should facilitate rapid quality control testing in the pharmaceutical industry and should be applicable to other therapeutic agents and products . Applicability to cosmetic products containing hydrogen peroxide is also demonstrated. Pharmacotherapy, 1993 Mar-Apr, 13(2 Pt 2), 34S - 38S Pharmacokinetic considerations in quinolone therapy; Nightingale CH; It is advisable to switch patients from parenteral to oral therapy as soon as practical . High volumes of distribution, coupled with relatively low protein binding, indicate that the quinolones are widely distributed outside extracellular fluid . Interactions with aluminum- or magnesium-containing antacids may be avoided by administering the antacids at least 2 hours after quinolone dosing . Some quinolones with high bioavailability (e.g., ofloxacin) are absorbed as reliably and completely after oral administration as when given parenterally, and dosage adjustments for these agents are unnecessary after sequential therapy . Treatment strategies may differ according to the route of drug elimination, and dosage adjustments are required in patients with renal failure who receive quinolones excreted primarily by the kidneys . Theophylline interactions may be more problematic in patients given quinolones that are primarily metabolized by the liver . Quinolones, which have concentration-dependent killing and a long postantibiotic effect, should be administered in the highest tolerated dosage . A method to assess the relative antibacterial efficacy of the quinolones uses the ratio of the Cmax:MIC90 of the organism, compared with a ratio derived from the NCCLS breakpoints for susceptibility. Br J Pharmacol, 1993 Mar, 108(3), 575 - 6 Active secretion of the fluoroquinolone ciprofloxacin by human intestinal epithelial Caco-2 cell layers; Griffiths NM et al.; The bidirectional transepithelial fluxes of ciprofloxacin, an antibacterial fluoroquinolone, across the human intestinal epithelial Caco-2 cell-line show marked asymmetry . Basal-to-apical flux of ciprofloxacin (10 microM) exceeds apical-to-basal flux indicating net secretion . Net ciprofloxacin secretion is abolished by azide/2-deoxy-D-glucose treatment, displays saturation kinetics (Km = 0.89 +/- 0.23 mM, Vmax 44.3 +/- 4.9 nmol cm-2.h) and competition by other fluoroquinolones . A specific, active secretion in Caco-2 epithelia may explain the transintestinal elimination of ciprofloxacin observed in pharmacokinetic studies in man. Antimicrob Agents Chemother, 1993 Mar, 37(3), 559 - 65 Mechanisms of action of cephalosporin 3'-quinolone esters, carbamates, and tertiary amines in Escherichia coli; Georgopapadakou NH et al.; Cephalosporin 3'-quinolone esters, carbamates, and tertiary amines are potent antibiotics whose antibacterial activities reflect the action of both the beta-lactam and the quinolone components . The biological properties of representative compounds from each class were compared in Escherichia coli . All compounds bound to the essential PBP 3, inhibited DNA gyrase, and caused filamentation in growing cells . To distinguish between cephalosporin- and quinolone-induced filaments, nucleoid segregation was also examined, as quinolones disrupt nucleoid segregation while the beta-lactams do not (N . H . Georgopapadakou and A . Bertasso, Antimicrob . Agents Chemother . 35:2645-2648, 1991) . The cephalosporin quinolone esters Ro 23-9424 and Ro 24-6392, at concentrations causing filamentation in E . coli ATCC 25922, did not affect nucleoid segregation after 1 h of incubation (cephalosporin response) but did not affect it after 2 h (quinolone response), indicating the release of free quinolone . Accordingly, only the quinolone response was produced in a strain possessing TEM-3, an expanded-spectrum beta-lactamase . The cephalosporin carbamate Ro 24-4383 and the tertiary amine Ro 24-8138 produced a quinolone response in E . coli ATCC 25922, though they produced a cephalosporin response in a quinolone-resistant strain . Carbamate and tertiary amine linkages are chemically more stable than the ester linkage, and both cephalosporin 3'-quinolone carbamates and tertiary amines are more potent inhibitors of DNA gyrase than are the corresponding esters . The results suggest that, while intact cephalosporin 3'-quinolone esters act as cephalosporins, carbamates and amines may possess both cephalosporin and quinolone activity in the intact molecule. Chemotherapy, 1993 Mar-Apr, 39(2), 128 - 31 Susceptibility of Brucella melitensis to the new fluoroquinolone PD 131628: comparison with other drugs; Qadri SM et al.; The antibacterial activity of PD 131628 was determined by the broth dilution method against 105 clinical isolates of Brucella melitensis . Fifty-two and ninety-nine percent of the isolates were inhibited by 0.06 and 0.12 microgram/ml of this quinolone, respectively . One strain which was resistant to 8 other fluoroquinolones, with a minimum inhibitory concentration (MIC) of > 4.0 micrograms/ml, did not show cross-resistance and had an MIC of 2.0 micrograms/ml . Of the 9 fluoroquinolones tested, PD 131628 was most inhibitory followed by CI-960 . All the strains were susceptible to conventional drugs like gentamicin, rifampicin, tetracycline and trimethoprim-sulfamethoxazole, with MICs ranging between 0.12 and 1.0 microgram/ml . PD 131628 did not exhibit in vitro synergy with any of the conventional drugs. J Dermatol Surg Oncol, 1993 Mar, 19(3), 216 - 20 Antibacterial activity of lidocaine in combination with a bicarbonate buffer; Thompson KD et al.; BACKGROUND . The antibacterial properties of lidocaine have been previously described . Recent reports indicated that the addition of NaHCO3 to lidocaine reduces the pain associated with the injection . This study was conducted to determine the antibacterial activity of lidocaine buffered with NaHCO3 . METHODS . Rates of killing of six species of bacteria were determined in the presence of buffered and unbuffered lidocaine . When bacteria were incubated with lidocaine buffered with NaHCO3 at either 25, 50, or 100 mEq/L, there was a decrease of > 99% of all bacteria tested over the 6 hours of the assay . This dramatic rate of killing was not observed in the unbuffered control preparations . RESULTS . The results of this study indicate that NaHCO3 enhances the killing effect that has been described for lidocaine alone . The inability to recover common pathogenic bacteria from biopsy specimens could be the result of exposure to local anesthetic agents such as lidocaine that are buffered with NaHCO3. Vestn Khir Im I I Grek, 1993 Mar-Apr, 150(3-4), 34 - 8 {The level of middle molecules in determining the degree of intoxication in patients with suppurative wounds}; Petrov VV et al.; For the estimation of the intoxication degree an analysis of dynamics of the level of medium-sized molecules (LMM) in blood serum was made in 71 patients with purulent wounds in different courses of the wound process . The results obtained were compared with the parameters of bacteriological and cytological characteristics . It was found that the 1.5 times elevation of LMM with values up to 0.380 units spoke of the compensated degree of intoxication with the following favourable course and disappearance by the 5th day of the postoperative period . While the 2-3 times elevation of LMM parameters--up to 0.710 units lies outside the limits of compensatory potentialities and complex antibacterial therapy normalized them by the 9th day . The comparison of dynamics of the parameters studied shows their clear correlative relationship. Immunopharmacol Immunotoxicol, 1993 Mar-Jun, 15(2-3), 307 - 19 Triazolobenzodiazepines exert immunopotentiating activities on normal human peripheral blood lymphocytes; Jirillo E et al.; Previous studies have demonstrated that benzodiazepines (BDZ) (e.g . diazepam) inhibit immune responsiveness . Since these drugs are largely used in psychiatric patients it is of great importance to verify the existence of different types of BDZ, which are not suppressive for the immune system . In this framework, our results indicate that alprazolam and triazolam, two triazolo-BDZ, do not modify in vitro phagocytosis and killing exerted by normal human polimorphonuclear cells and monocytes . On the contrary, they significantly enhance T lymphocyte-dependent antibacterial activity in normal donors . These data support the concept that triazolo-BDZ and, in particular, alprazolam may represent more appropriate drugs for the treatment of psychiatric patients (e.g . patients with phobic disorders and/or migraine) who display immunodeficits. Farmaco, 1993 Mar, 48(3), 443 - 6 Some nitroimidazole derivatives as possible antibacterial agents; Demirayak S et al.; In this study, six 1-{2(benzazol-2-yl)thioethyl}-2-methyl-5- nitroimidazole derivatives were synthesized . Antibacterial activities of the compounds obtained were examined and it was found that they are effective against aerobe bacteria. J Vet Dent, 1993 Mar, 10(1), 9 - 13 Effects of preactivated MC540 in the treatment of lymphocytic plasmacytic stomatitis in feline leukemia virus and feline immunodeficiency virus positive cats; Wiggs RB et al.; Photoactive compounds and drugs are used therapeutically as antibacterial, antiviral and antitumor agents . This report examines the use of a photoactive compound, preactivated merocyanine 540 (pMC540), in the treatment of stomatitis in two cats that are both feline immunodeficiency virus (FIV) positive . One of the cats was also feline leukemia virus (FeLV) positive . Dramatic short term improvement is reported with the dosage regimen and complications. Urol Nefrol (Mosk), 1993 Mar-Apr, (2), 22 - 4 {The use of efferent methods in the combined treatment of pyelonephritis in pregnant women}; Neimark AI et al.; After-treatment immune effects of therapy were assessed in 57 pregnant females with pyelonephritis . Eleven patients received standard antibacterial treatment (ABT), 25 patients ABT plus plasmapheresis, 21 patients underwent UV irradiation of blood and ABT . ABT alone resulted in improved general condition of the patients, in reduced renal inflammation, but it failed to remove completely signs of immunodeficiency, B-lymphocyte and Ig levels remained low . The combined treatment with UV blood irradiation and plasmapheresis promoted rapid disappearance of clinical and laboratory evidence indicating pyelonephritis . UV irradiation could not correct deficiency of cellular immunity, while adjuvant plasmapheresis led to a complete cure of immune deficiency symptoms. Urol Nefrol (Mosk), 1993 Mar-Apr, (2), 20 - 2 {The effect of Kuka mineral water on blood coagulability and fibrinolysis in patients with chronic pyelonephritis}; Mungalov NP; Chronic pyelonephritis (CP) is now ranking first among renal disorders, its incidence still tends to grow . Despite an impressive antibacterial armory, the efficacy of CP treatment remains low . In search of more effective and tolerable methods, the author directed his attention to CP balneotherapy . In addition to well-known health resorts where CP is successfully treated, Zheleznovodsk and Truskavets, a less known place is mentioned . It is the spa Kuka in the Transbaikal region . Mineral water Kukinskaya or Kuka (pH 6.18) comprises carbon dioxide, hydrocarbon-calcium and magnesium hydrocarbonates . The spa treatment was given to 65 CP patients . They underwent a general examination and evaluation of hemostasis . It was found that oral treatment with Kukinskaya mineral water produced a positive action on the blood coagulability and fibrinolysis . After the crenotherapy the pain persisted in 11.8%, leukocyturia in 9.9%, nephrogenic hypertension in 16.4% of the patients only . This proves the method effective for CP. J Biol Chem, 1993 Feb 25, 268(6), 4556 - 66 Characterization of a lipophilic antifolate resistance provoked by treatment of mammalian cells with the antiparasitic agent pyrimethamine; Assaraf YG et al.; We describe the characterization of an antitumor drug resistance following multiple step selection of hamster cells to the 2,4-diaminopyrimidines (DAP) metoprine, pyrimethamine (Pyr), and trimethoprim (Tmp) . Pyr and Tmp are DAP lipophilic antifolates currently used as antiparasitic and antibacterial antibiotics, respectively . Dihydrofolate reductase (DHFR) from hamster cells bore a low or poor affinity to these DAP as compared to the hydrophilic folate antagonist methotrexate (MTX) . Metoprine-resistant cells over-expressed DHFR enzyme and consequently displayed a high level of resistance to both hydrophilic and lipophilic antifolates including DAP but maintained wild type sensitivity to pleiotropic drugs involved in multi-drug resistance (MDR) . In contrast, although Pyr- and Tmp-resistant cells expressed parental levels of wild type DHFR, they displayed a high degree of resistance to DAP and, surprisingly, to the lipophilic MTX analogs piritrexim (PTX) and trimetrexate (TMTX), while maintaining sensitivity to MTX . These drug-resistant cells maintained wild type mRNA levels of the MDR gene product P-glycoprotein and showed collateral hypersensitivity to pleiotropic drugs . To study the underlying mechanism of this apparently new resistance phenotype, we have employed fluorescein-methotrexate (F-MTX) labeling of cells and its displacement by different antifolates . Parental AA8 and Pyr-resistant cells showed a similar level of F-MTX labeling, however, while DAP, TMTX, and PTX showed an efficient competitive displacement of F-MTX from AA8 cells, Pyr-resistant cells displayed a persistent retention of F-MTX labeling in the presence of high concentrations of these lipophilic antifolates . Pyr-resistant cells showed a wild type displacement of F-MTX with MTX . This DAP resistance phenotype was unstable as it was rapidly lost upon growth under nonselective conditions . Furthermore, when the antifolate resistance levels of Pyr-resistant cells were plotted versus the ratios of the 50% F-MTX displacement values obtained with resistant and parental AA8 cells, a good correlation (r2 > 0.98) was obtained . We conclude that Pyr-resistant cells possess a novel phenotype that derives its resistance to lipophilic antifolates solely from a predominant decrease in the accumulation of DAP and lipid-soluble analogs of MTX. Biochemistry, 1993 Feb 23, 32(7), 1695 - 706 Titration of histidine 62 in R67 dihydrofolate reductase is linked to a tetramer<-->two-dimer equilibrium; Nichols R et al.; R67 dihydrofolate reductase (DHFR) is an R-plasmid encoded protein that confers clinical resistance to the antibacterial drug trimethoprim . To determine whether an acidic titration in kinetic pH profiles is related to titration of histidines 62, 162, 262, and 362, the stability of tetrameric R67 DHFR has been monitored as a function of pH . For the pH range 5-8, tetrameric R67 DHFR reversibly dissociates into dimers, as monitored by ultracentrifugation and molecular sieving techniques . From the crystal structures of dimeric and tetrameric R67 DHFR {Matthews et al . (1986) Biochemistry 25, 4194-4204} (Narayana, Matthews, and Xuong, personal communication), symmetry-related histidines 62, 162, 262, and 362 occur at the two dimer-dimer interfaces and protonation of these residues could destabilize tetrameric R67 DHFR . Ionization of these histidines was confirmed by monitoring the chemical shifts of the C2 proton in NMR experiments, and best fits of an incomplete titration curve yield a pKa of 6.77 . Since tryptophans 38, 138, 238, and 338 also occur at the dimer-dimer interfaces, fluorescence additionally monitors the tetramer-two dimers equilibrium . When fluorescence was monitored over the pH range 5-8, a protein concentration dependence of fluorescence was observed and global fitting of three titration curves yielded Kd = 9.72 nM and pKa = 6.84 for the linked reactions: {formula: see text} Modification of H62, H162, H262, and H362 by diethyl pyrocarbonate stabilizes dimeric R67 DHFR and causes a 200-600-fold decrease in catalytic efficiency . Decreased catalytic activity in dimeric R67 DHFR is presumably due to loss of the putative single active site pore found in tetrameric R67 DHFR. Zentralbl Bakteriol, 1993 Feb, 278(1), 1 - 22 Lantibiotics--unusually modified bacteriocin-like peptides from gram-positive bacteria; Bierbaum G et al.; Lantibiotics are antibacterial peptides frequently produced by Gram-positive bacteria . They are distinguished by unique structural properties unprecedented so far in peptide chemistry . The most striking feature is the occurrence of intramolecular rings introduced by the thioether amino acids lanthionine and 3-methyllantionine . Additional usual amino acids such as didehydroalanine and didehydrobutyrine are found . Lantibiotics are produced from ribosomally synthesized prepeptides and the unusual amino acids are formed by post-translational modifications . This review summarizes the current knowledge on the biosynthetic mechanisms and enzymes taking part in biosynthesis, on the primary and spatial structures of the active peptides and the correlation between structural aspects and the antibacterial activity . Furthermore, the mode of action of type-A lantibiotics and the immunity phenomenon are described, and an outlook for future research and potential applications is given. Biochem Mol Biol Int, 1993 Feb, 29(2), 241 - 6 Mastoparan B, synthesis and its physical and biological properties; Yu HM et al.; Mastoparan B, a tetradecapeptide toxin (LKLKSIVSWAKKVL) isolated from the hornet (Vespa basalis) venom, was synthesized chemically . The physical and biological properties of both the native and synthetic peptides were studied and proved to be identical . Mastoparan B was found to have a potent antibacterial activity to both Gram negative and Gram positive bacteria. Endod Dent Traumatol, 1993 Feb, 9(1), 25 - 30 Effect of intracanal dressings on repair and apical bridging of teeth with incomplete root formation; Leonardo MR et al.; Periapical repair and apical bridging were studied in dog's teeth with incomplete root formation and induced chronic periapical lesions treated with different dressings . A total of 75 root canals from the upper and lower premolars of 4 dogs approximately 6 months of age were chemo-mechanically prepared and filled with the following dressings: antibacterial dressing consisting of a calcium hydroxide+camphorated p-monochlorophenol paste applied for 7 days and followed by monthly renewed calcium hydroxide paste as temporary dressing at 30, 60 and 90 days (Group A); antibacterial dressing consisting of camphorated p-monochlorophenol alone for 7 days, followed by temporary dressing with calcium hydroxide paste renewed at 30, 60 and 90 days (Group B) . A control group (Group C) received no dressings . Ninety days after the last calcium hydroxide paste (Groups A, B) and after the last irrigation/aspiration (Group C), the animals were killed, the maxillae and mandibles were removed, and the material submitted to routine histological processing and examination . Both root canal dressings, were of fundamental importance for apical repair and bridging . The apical bridging was predominantly complete in Group A, incomplete in Group B, and absent in Group C . The calcium hydroxide+camphorated p-monochlorophenol combination gave better results than camphorated p-monochlorophenol alone. J Antibiot (Tokyo), 1993 Feb, 46(2), 316 - 30 Orally active cephalosporins . III . Synthesis and structure-activity relationships of new 3-heterocyclicthiomethylthio-7 beta-{(Z)- 2-(2-aminothiazol-4-yl)-2-hydroxyiminoacetamido}-3-cephem-4 -carboxylic acids; Kume M et al.; 3-Heterocyclicthiomethylthio-7 beta-{(Z)-2-(2-aminothiazol-4-yl)-2- hydroxyiminoacetamido}-3-cephem-4-carboxylic acids (2) were synthesized . Their antibacterial activity and oral absorbability were much influenced by the structure of heteroaromatic moiety in the side chain at the 3-position of a cephem nucleus . In this cephalosporin series, 3-thiadiazolylthiomethylthiocephalosporins (2k, 2l and 2m) exhibited potent antibacterial activity against both Gram-positive and Gram-negative bacteria, whereas 3-(2-methyl-1,2,3-triazol-4-yl)thiomethylthiocephalosporin (2b) and 3-(pyridin-2-yl)thiomethylthiocephalosporin (2n) showed better oral absorption in mice than the other cephalosporins prepared . The structure-activity relationships of 2 are presented. Cell Mol Biol (Noisy-le-grand), 1993 Feb, 39(1), 105 - 14 Detection of mRNA encoding an antibacterial-metalloprotein (MPII) by in situ hybridization with a cDNA probe generated by polymerase chain reaction in the worm Nereis diversicolor; Salzet-Raveillon B et al.; Based on partial amino acid sequence of an antibacterial-metalloprotein (MPII) consisting of a N-terminal fragment (1-33th) and an 43 amino acids long internal fragment, two oligonucleotides primers were synthesized and used to generate a cDNA fragment by the PCR method . The specificity of the PCR synthesized 220 bp fragment was verified by hybrid-arrest translation and sequencing . In situ hybridization performed with this cDNA fragment on Nereis diversicolor whole body defined two specific sites of recognition: a cluster of cells floating in the coelom and two types of muscles (perineural and oblique) . Finally, the chronological expression of the MPII was postulated. Kinderarztl Prax, 1993 Feb, 61(1), 8 - 11 {Modification of pediatric lung function measurement by antibacterial filters}; Gruber W et al.; The risk of cross-infection by contaminated lung function equipment can be reduced by the use of antibacterial filters . These filters, however, should have no significant influence on flow measurements . We investigated the effect of a new filter (Pall PF 30) on lung function measurements in 92 children and adolescents with bronchial asthma and cystic fibrosis . In randomized sequence, flow-volume curves and spirometry were registered in the whole body plethysmograph . Values measured with filter correlated closely to those registered without; individual values remained close to the line of identity . With high flow rates, however, there was a minimal tendency towards lower measurements with filter; this damping effect was flow-dependent and remained of a clinically insignificant dimension. J Antimicrob Chemother, 1993 Feb, 31 Suppl B, 11 - 21 Pharmacokinetic aspects of antibacterial prophylaxis; Reeves DS et al.; Effective prophylaxis against infection can only occur when the antibacterial achieves suitable concentrations at the site of potential infection . This review discusses how the pharmacokinetics of systemically applied prophylaxis and the factors governing the distribution of locally applied antibacterials influence the outcome of prophylactic therapy . While the choice of route of administration for systemic prophylaxis rarely poses a problem, the effective concentrations required at the site of potential infection are unclear and may possibly be less than those needed for therapy of established infection . In some tissues there may be special considerations for the access of antibacterial from the blood, although for the large majority of sites the evidence is that access occurs without difficulty and is perhaps only limited by plasma protein binding of antibacterial . Locally applied antibacterials may have difficulty in reaching their site of action but this can often be overcome by their application at very high concentrations. Fundam Appl Toxicol, 1993 Feb, 20(2), 257 - 63 Effects of difloxacin on the metabolism of glycosaminoglycans and collagen in organ cultures of articular cartilage; Burkhardt JE et al.; Fluoroquinolones, including difloxacin, are potent antibacterial compounds which, as a side effect, cause lesions in articular-epiphyseal cartilage complexes (AECC) of growing animals . To evaluate the effects of difloxacin on the structure of AECC and the metabolism of sulfated glycosaminoglycans (GAG) and collagen, explants of AECC were obtained from 18 healthy, 3-month-old Beagle dogs and cultured in medium which either had no difloxacin or had the drug at one of three concentrations (40, 80, or 160 micrograms/ml) . Rates of synthesis of GAG and collagen were reduced by concentrations of difloxacin that were at or above 80 micrograms/ml . The rate of synthesis of total protein, however, was reduced only at the highest dose level . Catabolism of GAG and collagen was unaffected by the treatment . The principal ultrastructural changes in affected chondrocytes were distension of rough endoplasmic reticulum with electron-dense material that was probably protein, and vacuolation of cytoplasm . Structural changes were not observed in the extracellular matrix . It, therefore, appeared plausible that difloxacin affected chondrocytes by interfering with secretion of the matrix components, GAG and collagen. Mol Pharmacol, 1993 Feb, 43(2), 191 - 9 Quinolone antibacterial agents: relationship between structure and in vitro inhibition of the human cytochrome P450 isoform CYP1A2; Fuhr U et al.; The inhibitory effect of 44 quinolone antibacterials and derivatives (common structure, 4-oxoquinoline-3-carboxylic acid) on cytochrome P450 isoform CYP1A2 activity was tested using human liver microsomes and caffeine 3-demethylation as a specific test system for this enzyme . By direct comparison of molecules differing structurally in only one position, the following structure-activity relationships were found . 3'-Oxo derivatives had a reduced or similar activity and M1 metabolites (cleavage of piperazinyl substituent) had a greater inhibitory activity, compared with the parent molecule . Alkylation of the 7-piperazinyl substituent resulted in a reduced inhibitory potency . Naphthyridines with an unsubstituted piperazinyl group at position 7 displayed a greater inhibitory potency than did corresponding quinoline derivatives . Derivatives with a fluorine substitution at position 8 had only a minor effect . Molecular modeling studies with inhibitors and caffeine showed that it is possible to explain the potency of the quinolones to inhibit CYP1A2 on a molecular level . The keto group, the carboxylate group, and the core nitrogen at position 1 are likely to be the most important groups for binding to the active site of CYP1A2, because the molecular electrostatic potential of all inhibitors is very similar to that of caffeine in these regions . The presence of a piperazinyl substituent, however, seems to be no prerequisite for inhibitory potency . Finally, an equation to estimate the potency to inhibit CYP1A2 was developed by quantitative structure-activity relationship analysis. FEBS Lett, 1993 Feb 1, 316(3), 233 - 40 A new family of basic cysteine-rich plant antifungal proteins from Brassicaceae species; Terras FR et al.; Out of seeds of 4 Brassicaceae species, 7 antifungal proteins were isolated which are nearly identical to 2 previously characterized radish seed antifungal proteins . These basic proteins, multimers of a 5 kDa polypeptide, specifically inhibit fungal growth . One of the antifungal proteins has decreased antifungal activity and an increased antibacterial activity . In addition, the previously described antifungal activity of the radish seed 2S albumins was extended to the 2S albumins of the seeds of the 4 other Brassicaceae species . A 2S albumin-like trypsin-inhibitor from barley seeds was found to have much less activity against fungi. Bratisl Lek Listy, 1993 Feb, 94(2), 81 - 7 {The effect of ethanol on the occurrence of peptides with antibacterial effects in the rat myocardium}}; Adam J et al.; The effect of 7% ethanol on the peptide content in the myocardium was studied during prolonged exposition . The protein-free extract from the myocardium of controls as well as experimental groups following 1-8 weeks ethanol administration contained peptides with antibacterial activity . Long-term ethanol administration resulted in changes in physico-chemical properties of peptides both compared with controls and also among the experimental groups mutually . The changes were manifested by differences in the elution profiles following gel chromatography and RF values after electrophoresis or by different amino acid composition . The results are compared with the influence of peptides on the growth of bacterial cultures S . aureus . Ethanol administration induced diminution of the diameter of the inhibitory zones . This effect was most marked in the group fed with ethanol for 3 and 8 weeks . (Fig . 5, Ref . 17.) Acta Virol, 1993 Feb, 37(1), 29 - 40 Biological properties of chloroform/methanol extracts of Coxiella Burnetii; Tokarevich NK et al.; Biological properties of antigens of whole cells of C . burnetii in phase I (WCI), their residue (CMR) and extract (CME) obtained by extraction of C . burnetti with chloroform/methanol mixture were subjected to a comparative study . It was shown that CME is able to react specifically with sera containing antibodies against WCI . The inoculation of animals with CME, but not with WCI and CMR does not cause changes of humoral and cell immunity to Coxiella and does not strengthen nonspecific antibacterial activity, but it can stimulate the formation of antibodies . Morphological changes of internal organs of mice were most expressed after the CMR inoculation and were practically absent after the CME inoculation. J Can Dent Assoc, 1993 Feb, 59(2), 171 - 4, 177-9 Caries prevalence in xerostomic individuals; Papas AS et al.; Saliva, via its lubricating, cleansing, remineralizing, antibacterial, and buffering actions, is an important protective factor for both dentition and soft tissue . Xerostomia is commonly found in older individuals due to the use of medications or medical conditions, such as Sjogren's, which directly affect salivary gland function . A xerostomic subgroup (n = 60), mean age = 60, 66 per cent female) of the Nutrition and Oral Health Study (n = 370) was reexamined for caries . Unstimulated and two-per-cent citric-acid stimulated parotid and submandibular/sublingual salivary flow rates were determined . This group was matched for number of teeth, age, sex, and alcohol and smoking habits with a medication-free subgroup (n = 60) . Active root and coronal caries were found to be significantly higher in the xerostomic subgroup than in a matched subgroup of medication-free individuals . The mean DFS for the xerostomic subgroup was 45.4 +/- 21.7 for coronal caries and 5.3 +/- 5.8 for root caries . The mean number of teeth was 21.8 . The mean DFS in the medication-free subgroup was 36.5 +/- 22.1 for coronal caries and 3.2 +/- 3.2 for root caries . The mean DFS in the xerostomic subgroup for coronal and root caries was statistically significantly higher (p < 0.05) . The odds ratio was 2.89 for coronal caries and 3.27 for root caries in the xerostomic versus the medication-free subgroup . Caries varied inversely with salivary flow rate . The difference in flow rates for those in the lowest and highest quartile for coronal caries experience (DFS) in the xerostomic subgroup was found to be statistically significant (p < 0.05).(ABSTRACT TRUNCATED AT 250 WORDS) Rinsho Ketsueki, 1993 Feb, 34(2), 119 - 27 {Clinical study of recombinant human granulocyte-colony stimulating factor (KW-2228) in pediatric field . 2 . Effectiveness on neutropenia associated with administration of anticancer agent and safety}; Sakurai M et al.; The effect of KW-2228, a derivative of recombinant human granulocyte colony stimulating factor, on neutropenia associated with chemotherapy was studied in pediatric patients with malignant tumor . To patients repeatedly treated with the same chemotherapy, KW-2228 was administered subcutaneously at 1 microgram/kg or intravenously at 2 micrograms/kg once a day in the 2nd course of the chemotherapy . During the administration term of KW-2228, the nadir of neutrophils went up, and the duration of neutrophil count under 500/microliters as well as the interval for recovery of the count to 500/microliters were remarkably shortened, compared with those during the observation term . Further, the duration of fever in patients and the administration days of antibacterial agent were also reduced . The effective rate judged by attending doctors was as high as 78.9%, consisting of 83.3% in 42 cases of subcutaneous administration and 73.5% in 34 cases of intravenous administration . Side effects such as slight skeletal pain and slight fever in one case each (2.3% in total) were improved without treatment . It is concluded that KW-2228 may be a useful drug for treatment of neutropenia associated with chemotherapy in pediatric patients with malignant tumor. Mutat Res, 1993 Feb, 298(4), 227 - 36 High capacity in vitro micronucleus assay for assessment of chromosome damage: results with quinolone/naphthyridone antibacterials; Ciaravino V et al.; A high capacity in vitro micronucleus assay was developed to evaluate the ability of selected 6-fluorinated quinolone and naphthyridone antibacterial compounds to induce micronuclei (MN) in vitro in V79 Chinese hamster lung cells . Log-phase cells in six-well cluster dishes were exposed for 3 h in the absence of S9 to 34 compounds . After treatment, cells were refed with media containing cytochalasin B, incubated for 16 h, and harvested for cell-cycle kinetics (CCK) and MN analyses . The quinolones tested were grouped according to the substituent at the 8-position . All 4 compounds having a halogen substitution at position 8, five of the six 8-trifluoromethyl quinolones, and all eight 8-methoxy-substituted compounds induced a significant increase in MN . Only 5 of the 10 naphthyridone compounds tested, having a variety of substituents at the 7-position, were inducers of MN and the overall magnitude of the response was less than with the quinolones . The minimum clastogenic concentration for the quinolones ranged from 4 to 400 micrograms/ml and for the naphthyridones this range was from 22.5 to 100 micrograms/ml . In the groups examined, napthyridone compounds were less likely than quinolones to induce in vitro MN, particularly when the substituent at the 7-position in the naphthyridone contains some bulk (methyl groups) around the amine side-chain . Most of the quinolones tested induced MN, irrespective of the substituents at positions 7 or 8. Clin Ther, 1993, 15 Suppl A, 3 - 11 Controlling the costs of antibiotic resistance; North D; Excessive and inappropriate use of antibiotics in hospitals contributes to the development of antibiotic resistance and to increased hospital costs . Denver's three major teaching hospitals have developed a multifaceted approach that has curbed inappropriate antibiotic prescribing and reduced costs for antibiotic purchases . A joint antibiotic-use committee with representatives from each hospital's pharmacy and therapeutics committee developed a single antibiotic formulary for systemically active antibacterial agents, based on simplicity, clinical efficacy, previous use patterns, local resistance patterns, and relative cost . This formulary includes primary agents, ordered at the prescriber's discretion; secondary agents, ordered only for an approved condition; and restricted agents, which had been used excessively or inappropriately in the past, and are now dispensed only after consultation with infectious disease specialists . A computerized antibiotic order-entry program at the Denver V.A . Medical Center requires all physicians to enter antibiotic requests through a centralized computer system . Drug utilization is evaluated using data collected from the computer data base and in vitro data from the microbiology laboratory . In addition, appropriate antibiotic prescribing and infection control practices are taught in an education program for physicians, nurses, and other health care workers. Int J Clin Pharmacol Res, 1993, 13(1), 11 - 20 Pharmacokinetic and bacteriological study of cefadroxil-salicylate and josamycin-salicylate drug regimens; Dellamonica P et al.; Eye, nose, throat and bronchopulmonary infections are frequently associated with inflammatory symptoms . This often leads the clinician to prescribe a combination of an anti-inflammatory and an antibiotic . Cefadroxil and josamycin are among the antibiotics most frequently used in these infections, and they are often combined with acetylsalicylic acid in various pharmaceutical formulations . The study of possible pharmacokinetic and bacteriological interactions was performed in healthy volunteers who received in a crossover protocol each of the two antibiotics, either alone or combined with acetylsalicylic acid or lysine acetylsalicylate . No marked pharmacokinetic interaction was noted except an increase in the AUC for plasma concentrations of cefadroxil when combined with a salicylate . A greater uniformity of kinetic profiles was seen with cefadroxil than with josamycin . Lastly, with the exception of one strain, the salicylates did not alter the antibacterial activity of cefadroxil. Perit Dial Int, 1993, 13(2), 149 - 54 Peritoneal dialysis catheter exit-site care: results of an international survey; Prowant BF et al.; A survey was developed to determine the prevalence of specific components of postoperative and chronic peritoneal catheter exit-site care procedures . Surveys were mailed to approximately 1800 participants of the 1991 Peritoneal Dialysis Conference; 585 surveys (80.6% from the United States and 96% from adult units) were analyzed . The most frequent components of postoperative exit-site care were the use of prophylactic antibiotics, daily dressing changes, procedures limited to specially trained staff, use of sterile technique, povidone iodine and hydrogen peroxide as cleansing agents, and gauze dressings . The most frequent components of chronic exit-site care procedures were daily care done with shower or bathing, antibacterial or pure soap for cleansing, hydrogen peroxide only as needed, catheter stabilization, dressings optional, and gauze dressings when used . Twice daily exit care, change in cleansing agent, and topical antibiotics were recommended for inflamed or infected exit sites . There were significant differences between the United States and other locations, particularly in the type of cleansing agent, use of hydrogen peroxide, and use of dressings for chronic care . Pediatric programs (all located in the United States or Canada) differed somewhat from adult programs in North America . Pediatric patients and their families were significantly more likely to be trained to do postoperative dressing changes and significantly less likely to perform exit-site care at the time of showering or bathing. Eur J Ophthalmol, 1993 Jan-Mar, 3(1), 26 - 30 Imipenem reaches therapeutic concentrations in aqueous humor, as determined by HPLC; Bologna M et al.; The majority of ocular infections in the industrialized countries arise after surgical interventions . An appropriate antibacterial prophylaxis is therefore highly desirable in eye surgery . We used high performance liquid chromatography (HPLC) to measure the concentrations reached by imipenem, a modern wide-spectrum beta-lactam antibiotic, in plasma and aqueous humor of 26 patients scheduled for cataract surgery . Even a single 500 mg dose of imipenem achieved therapeutic levels of the molecule for the most common ophthalmic pathogens (1 microgram/ml or above) in the aqueous humor within one to two hours after administration . This drug may therefore be suitable for antibacterial prophylaxis in eye surgery. Rev Med Panama, 1993 Jan, 18(1), 62 - 9 {Bioessay with brine Artemia to predict antibacterial and pharmacologic activity}; Sanchez C et al.; The Brine Shrimp Test (BST) is a simple and inexpensive method to test cytotoxity, to biodirect phytochemical fractionation of natural products and as a predictor for antitumor and pesticidal activity . In this work, the BST test, an antibacterial test and the rat hippocratic screening test were used on 25 plant extracts and fractions, to evaluate the correlation, if any, between the BST and the others . Preliminary results show that the BST is not a predictor of antibacterial activity nor the hippocratic screening test. Jpn J Antibiot, 1993 Jan, 46(1), 18 - 30 Pharmacological effects of cefclidin on the central nervous system; Kaneko T et al.; The effects of cefclidin (CFCL), a novel antibacterial agent, on the central nervous system (CNS) were examined in a variety of animal models . The effects of cefazolin (CEZ) were also examined for comparative purposes . In the animal models used CFCL whilst having some effects at the doses examined, failed to show an overall consistent effect on the CNS . In contrast CEZ produced changes in the parameters measured which were generally consistent with a proconvulsant action. Gynecol Obstet Invest, 1993, 35(2), 108 - 13 Intrauterine infections and their association with stillbirth and preterm birth in Maputo, Mozambique; Axemo P et al.; Subclinical intrauterine infections during pregnancy in Mozambican women were studied in an attempt to elucidate their potential association with adverse pregnancy outcome, particularly stillbirth and preterm birth . A total of 39 stillbirths and 21 preterm live births were compared with 121 term live births . Extraplacental membranes and amniotic fluid were studied to ascertain the presence or absence of chorioamnionitis and of antibacterial activity in amniotic fluid . It was found that signs of maternal subclinical disease in extraplacental membranes in combination with an absence of antibacterial activity in amniotic fluid was overrepresented in stillbirths and preterm births in relation to term live births . A tentative conclusion is that a lack of antibacterial activity in amniotic fluid and established chorioamnionitis represent a vicious combination with strongly negative significance for the fetal outcome. Clin Pharmacokinet, 1993 Jan, 24(1), 46 - 58 Clinical pharmacokinetics of newer antibacterial agents in liver disease; Westphal JF et al.; Liver disease may produce significant, albeit highly variable, effects on the pharmacokinetic behaviour of antibiotics in serum . Drug disposition may be altered through several pathophysiological mechanisms including reduced hepatobiliary clearance, and modifications in the volume of distribution induced by albumin synthesis deficiency or portal hypertension-related ascites .