Antimicrobial

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 . Antibacterial agents are not affected by potential alteration in hepatic first-pass effects . Only liver cirrhosis-induced effects on serum pharmacokinetics of antibiotics have been extensively studied, unlike those possibly produced by other forms of liver disease . In liver cirrhosis, pharmacokinetic alterations of nearly all beta-lactam or quinolone agents appear not to be marked enough to require dosage adjustment, provided that renal function stays normal . Adaptation in therapeutic schedule, however, is warranted for those drugs that are substantially cleared by the hepatobiliary system, namely mezlocillin, clindamycin, erythromycin, pefloxacin, enoxacin, antituberculous agents or nitroimidazole derivatives . Special caution should also be exercised when using aminoglycosides or vancomycin because of the wide interpatient variability of their pharmacokinetic disposition and their toxic potential . When renal function is impaired and there is an increased volume of distribution due to ascites, as frequently observed in severe liver insufficiency, the elimination half-life of most antibiotics is markedly prolonged, resulting in potential side effects due to drug accumulation . Accordingly, dosage adjustment applies to all drugs . In this regard, it should be remembered that delineating the dosage guidelines for a given antibiotic on the basis of reported pharmacokinetic parameters in patients with liver cirrhosis is awkward and probably of limited value . This pattern is ascribed to large interpatient variability in the active hepatic cell mass, the degree of portal hypertension and the alteration of serum binding capacity . Furthermore, there is no way of predicting accurately the extent of liver insufficiency in an individual patient . Dosage reduction is thus done empirically in most cases . Whenever possible, direct measurements of serum antibiotic concentrations should be the reasonable approach to manage antibiotic therapy in this kind of clinical condition.

Wien Klin Wochenschr, 1993, 105(3), 84 - 8
{Antibacterial chemotherapy of "septic kidney"}; Janetschek G et al.; In the present retrospective study we report on antibacterial chemotherapy in patients suffering from a septic kidney . The results were documented in a course table, in which the septic parameters were divided into scores from 0 to 4 allowing to follow each patient's course with respect to the indicated scores . Two antibacterial substances were applied as short infusions with intervals of 4-6 hours between the administration of the different substances (Innsbruck scheme of chemotherapy) . In all cases within 6 days from the onset of this therapy the septic parameters turned to normal values . None of the 24 patients suffering from a severe course of urosepsis, all treated at the University Hospital of Urology in Innsbruck between 1980 and 1990, died.

J Antimicrob Chemother, 1993 Jan, 31(1), 37 - 45
Influence of sub-inhibitory concentrations of antibacterials on the surface properties and adhesion of Escherichia coli; Loubeyre C et al.; The effect of sub-inhibitory concentrations of antibacterials, including quinolones, on the surface properties of a uropathogenic strain of Escherichia coli was examined . The effect on the charge and hydrophobicity of the cell surface was assessed by means of partition between two aqueous phases, polyethylene glycol and dextran . Antibiotics at 1/8 x MIC inhibited adhesion to uroepithelial cells, and induced an increase in bacterial charge and hydrophobicity . Inhibition of adhesion correlated with increased charge, but not with hydrophobicity . The influence of magnesium on the inhibition of adhesion by sub-MICs of pefloxacin was also investigated . Loss of the anti-adhesive property of pefloxacin was observed with increasing magnesium concentrations, suggesting that quinolones should be free from magnesium to induce an inhibition of adhesion . Examination by electron microscopy showed a disappearance of fimbriae following treatment of E . coli cells with 1/8 x MIC of pefloxacin.

J Antibiot (Tokyo), 1993 Jan, 46(1), 25 - 33
Epocarbazolins A and B, novel 5-lipoxygenase inhibitors . Taxonomy, fermentation, isolation, structures and biological activities; Nihei Y et al.; New 5-lipoxygenase inhibitors, designated epocarbazolins A and B, were isolated from the culture broth of Streptomyces anulatus T688-8 . These compounds showed potent rat 5-lipoxygenase inhibitory activity with weak antibacterial activity . Structural studies revealed that epocarbazolins are new carbazole antibiotics having a novel substitution pattern and an epoxide in the side chain.

J Antibiot (Tokyo), 1993 Jan, 46(1), 177 - 92
Orally active cephalosporins . II . Synthesis and structure-activity relationships of new 7 beta-{(Z)-2-(2-aminothiazol-4-yl)-2-hydroxyiminoacetamido}-cephalospori ns with 1,2,3-triazole in C-3 side chain; Kume M et al.; The synthesis, antibacterial activity and oral absorbability of 7 beta-{(Z)-2-(2-aminothiazol-4-yl)-2-hydroxyiminoacetamido}-3 -(1H-1,2, 3-triazol-4-yl)thiomethylthio-3-cephem-4-carboxylic acid (1g) and related compounds are described . Their oral absorbability was influenced by the spacer length between C-3 of a cephem nucleus and C-4' of 1,2,3-triazole . The SCH2S structure was also found to contribute to their good oral absorption . The quantitative relationship between the bioavailability and the spacer length of cephalosporins (1a-1n) is discussed.

J Antibiot (Tokyo), 1993 Jan, 46(1), 167 - 76
Use of amino acid N-carboxy anhydride in the synthesis of peptide prodrug derivatives (including beta-chloroalanyl) of C4-beta-aminoalkyl carbapenems . In vitro and in vivo activities; Rao VS et al.; Mono- and dipeptide derivatives of C4-beta-aminoalkyl carbapenems were synthesized by the use of amino acid N-carboxy anhydride for the peptide bond formation . They were shown to act as prodrugs in vivo while imparting the much desired chemical stability . The beta-chloroalanyl derivative was suggested to act, in part, as a "dual-purpose" antibacterial.

J Antibiot (Tokyo), 1993 Jan, 46(1), 141 - 8
Enzymatic dimerization of penicillin X; Agematu H et al.; Penicillin X methyl ester was transformed into three types of dimer by laccase from Coriolus versicolor . The dimers are considered to be formed by free-radical addition of phenoxy radicals produced by laccase . The enzyme reaction with the ester as substrate was more suitable for forming dimers than that with the sodium salt as substrate . Penicillin X pivaloyloxymethyl ester was also transformed into a dimer, which had antibacterial activity in the presence of esterase.

Am Pharm, 1993 Jan, NS33(1), 41 - 6
New antibacterial agents; Hussar DA; These seven agents offer wider choices in drug regimens, and the use of certain agents should improve patient compliance because of less frequent dosing and shorter duration of treatment . Treatment indications can be expected to expand as additional studies are conducted.

Oncol Nurs Forum, 1993 Jan-Feb, 20(1), 69 - 75
Intravenous immunoglobulin in oncology nursing practice; Timmerman PR; Intravenous immunoglobulin (IVIG) is a concentrated form of IgG, also known as gamma globulin, that is derived from the pooled serum of a large number of donors . IVIG contains many types of antibacterial and antiviral antibodies . While its use in certain clinical conditions (e.g., severe combined immunodeficiency) is well-established, other indications still are under investigation . Along with nursing implications for use in inpatient and outpatient settings, the role of IVIG in treating immune thrombocytopenic purpura, chronic lymphocytic leukemia, treatment-induced neutropenia and thrombocytopenia, bone marrow transplantation, and AIDS will be discussed.

Mikrobiyol Bul, 1993 Jan, 27(1), 27 - 30
{The antibacterial activity of the amniotic fluid during the last week of pregnancy}; Kiraz N et al.; Amnion fluid samples were obtained from 100 pregnant women in the last week of pregnancy just before in labor . In detecting of antibacterial effectiveness, S . aureus ATCC 29213, E . coli ATCC 25922 and S . agalactiae ATCC 13813 strains were used . Antibacterial effectiveness of amnion fluid to these bacteria are found respectively as; 74%, 63% and 73.9%.

Perit Dial Int, 1993, 13 Suppl 2, S313 - 5
Exit-site care--is it time for a change?
Hasbargen BJ, Rodgers DJ, Hasbargen JA, Quinn MJ, James MK.
Peritoneal catheter exit-site infections (ESI's) continue to impact significantly on morbidity and catheter longevity . The controversy concerning protocols for daily exit-site care continues for frequency, methodology, cleansing agent, and dressing . Routine daily exit-site care prior to January 1991 consisted of daily showers using liquid soap, povidone scrub, rinsing the shower, and drying with a 4 x 4-in . gauze pad . Catheters have always been immobilized, either with tape or an immobilizing device . Hydrogen peroxide was used only when needed to soften crust formation prior to showering . A light dressing, usually 2 x 2 in., was optional . A recent survey revealed that povidone iodine was the antiseptic of choice for catheter care in 75% of the respondents . However, povidone iodine irritates and dries the skin predisposing it to infection . ESI's are prospectively monitored as part of our quality improvement (QI) program . An incidence of 0.76 episodes/patient-year was noted between January 1989 and May 1991 . Given the relative high frequency of ESI's, the protocol was modified and introduced during the January-May 1991 time frame . Routine care now consists of daily showers using only CC-500, a gentle antibacterial cleaner (Care-Tech Laboratories, Inc.), rinsing in the shower, and drying with a 4 x 4-in . gauze . Use of hydrogen peroxide and dressings has remained the same . Additionally, a protocol addressing the prophylaxis for traumatized exist sites was initiated . The incidence of ESI's has dropped significantly to 0.12 episodes/patient-year . Although our population size is small (n = 18), this study does point out the utility of prospectively monitoring trends for appropriate indicators within a QI program.(ABSTRACT TRUNCATED AT 250 WORDS)

Chem Pharm Bull (Tokyo), 1993 Jan, 41(1), 132 - 8
Synthesis and structure-activity relationships of 7-(3'-amino-4'-methoxypyrrolidin-1'-yl)-1-cyclopropyl-6,8-difluoro-1,4- dihydro-4-oxoquinoline-3-carboxylic acids; Okada T et al.; A new series of quinolone derivatives 3a--1 bearing 3-amino-4-methoxypyrrolidines of different configurations and chirality were synthesized and their antibacterial activities as well as some of their toxicological properties were examined . As predicted by our previous quantitative structure-activity relationships (QSAR) analysis of C-7 heterocyclic amine substituted quinolonecarboxylic acid antibacterial agents, these pyrrolidine derivatives showed higher in vitro and in vivo antibacterial activities against both gram-positive and gram-negative bacteria than the analogs bearing various 3-substituted azetidines . Furthermore, the amino and methoxy substituent groups on the pyrrolidine ring exhibited strong configurational and chiral effects on the in vitro and in vivo antibacterial activities of these compounds: (1) cis compounds showed higher antibacterial activities against most of the pathogens examined; (2) N-methylation of the 3-amino group on the pyrrolidine ring lowered in vitro but not in vivo antibacterial activities, particularly leading to superior in vivo anti-pseudomonal activity; (3) the (3'S,4'R)-derivative showed substantially higher activity that the (3'R,4'S)-one . These findings led to the selection of compound 3k for further evaluation as it possessed the highest in vivo antibacterial activity and no cytotoxicity.

Chem Pharm Bull (Tokyo), 1993 Jan, 41(1), 126 - 31
Quantitative structure-activity relationships of antibacterial agents, 7-heterocyclic amine substituted 1-cyclopropyl-6,8-difluoro-4-oxoquinoline-3-carboxylic acids; Okada T et al.; Quantitative structure-activity relationships (QSAR) of various 7-(3-substituted-azetidin-1-yl)-1-cyclopropyl-6,8-difluoro-1,4-dih ydro-4- oxoquinoline-3-carboxylic acids, 14-25, were studied to clarify the structural requirements for 3-substituted azetidines to potentiate antibacterial activity . A good parabolic relationship seemed to exist between the relative mean antibacterial activity indices against five representative gram-negative bacteria, GNM, and the calculated hydrophobic parameters, CLOG P, of these molecules . The CLOG P value of the most potent derivative was predicted to be around 2.3 . On the other hand, against five representative gram-positive bacteria, the relative mean antibacterial activity indices, GPM, remained high and rather constant regardless of structural variation in the azetidine moiety . In order to confirm these findings, the QSAR analysis was extended with success to the quinolonecarboxylic acids, 26-34, which bear various substituted pyrrolidine, piperazine and piperidine derivatives instead of azetidines . The findings showed that the introduction of any amide substituent group to these heterocyclic amine moieties would lead to marked decrease in GNM, whereas incorporation of some amino substituent groups at a position two or three carbons remote from the N-1 position resulted in great enhancement of GNM . As azetidine quinolones exhibited somewhat low in vivo antibacterial activities, possibly reflecting their lesser bioavailability, we finally selected 3-amino-4-methoxypyrrolidine as one of the most promising C-7 substituent groups based on our QSAR analysis.

Crit Rev Oral Biol Med, 1993, 4(3-4), 599 - 604
A contemporary view of salivary research; Mandel ID; The past 50 years of salivary research has been marked by a series of changing perceptions as new techniques and technologies have illuminated the complexities of the secretory mechanism, salivary composition, and function . The modern era began with the innovations of electrophoresis, chromatography, histochemistry, immunochemistry, electron microscopy, and microphysiology . The idea of saliva as primarily a digestive fluid composed of salts, amylase, and mucin was rapidly broadened to encompass a wide spectrum of protective proteins with the dual responsibility of protecting both hard and soft tissues . Characterization of the secretory IgA and nonimmunological antibacterial systems and the proteins responsible for the regulation of calcium and phosphate levels dominated the research in the 1960s and 1970s . An appreciation of the nature, formation, and role of the salivary pellicle and the interplay between bacterial adherence and agglutination provided a clinical thrust . Morphologists and physiologists redefined the secretory process on a molecular level . The 1980s saw the union of structure and function, both in terms of synthesis and release of the secretory products and their specific roles in the oral cavity in health and disease . The excitement of the 1990s is in the genetic control of processes and products, elucidating the mechanisms, and using the information to improve on nature: an era of great expectations and hubris . This article is essentially a personal guided tour through the past 50 years of salivary research.

Pneumonol Alergol Pol, 1993, 61(3-4), 189 - 90
{Foreign body of the bronchus in adults}; Piotrowicz P et al.; Two cases of endobronchial foreign bodies are presented . In both an uneventful clinical course following removal of the foreign body and antibacterial therapy was observed . The authors diagnostical problems in cases with scant symptoms, especially presence of non-specific symptoms and uncharacteristic medical history.

Eur J Cancer, 1993, 29A(9), 1274 - 9
Ceftriaxone versus latamoxef in febrile neutropenic patients: empirical monotherapy in patients with solid tumours; Oturai PS et al.; 121 patients with 132 febrile episodes were randomised to ceftriaxone or latamoxef monotherapy in order to compare antibiotic efficacy in neutropenic patients treated with cytotoxic chemotherapy for solid tumours . In 80 evaluable episodes no significant differences were observed between the two groups with respect to efficacy and fatal failure rates . Of episodes treated with ceftriaxone, 67% showed a favourable clinical response vs . 61% in the latamoxef group . The clinical response rates in episodes with documented bacterial infections were 67 and 56% in the two treatment groups . In 18% of the episodes with documented initial infections the patients died of presumably uncontrolled infection . The convenient once daily dosage schedule combined with fewer severe adverse reactions favours the use of ceftriaxone instead of latamoxef . Although a relative high degree of response was seen, empirical antibiotic monotherapy apparently does not offer a sufficient antibacterial cover in infections in this type of patient with defective host immunity.

Khirurgiia (Mosk), 1993 Jan, (1), 13 - 7
{The differential diagnosis and therapeutic procedure in nontumorous mechanical jaundice and cholangitis}; Shalimov AA et al.; The results of operative treatment of 2,875 patients with obstructive jaundice and cholangitis of nonneoplastic genesis are generalized . On the basis of rich clinical experience, the authors substantiate the principles of differential and topical diagnosis in obstructive jaundice and purulent cholangitis as well as the optimal therapeutic tactics in obstruction of the bile ducts of various levels and types . Problems are elaborated with respect of complex antibacterial therapy with the use of various routes of administration, including administration in the pre- and intraoperative period for preventive purposes.

Ophthalmic Res, 1993, 25(2), 128 - 36
Intravitreal flomoxef sodium in rabbits; Mochizuki K et al.; We studied the intraocular concentration of flomoxef sodium in nonvitrectomized and vitrectomized eyes of albino rabbits after intravenous administration of 100 mg/kg flomoxef sodium . The concentration of flomoxef sodium in the vitreous body was undetectable (< 0.1 micrograms/ml) in nonvitrectomized eyes . Retinal toxicity of flomoxef sodium was investigated with ophthalmoscopy, electroretinography (ERG) and light microscopy after intravitreal injection of 200, 500, 1,000 and 2,000 micrograms flomoxef sodium in albino and pigmented rabbits . No ERG changes were induced with 200 micrograms . Other higher doses caused transient ERG changes . After the 200-micrograms injection, the intravitreal concentration decreased exponentially, the half-life being 4.4 h . The antibacterial activity, broad coverage and low intravitreal toxicity of flomoxef sodium suggest that this compound may be used to treat bacterial endophthalmitis.

Infection, 1993, 21 Suppl 1, S10 - 3
{Possibilities for the use of basic cephalosporins}; Rodloff AC et al.; The always growing number of cephalosporins constitutes a significant part of the betalactam antibiotics . Depending on antibacterial spectrum and in vitro activity, different groups, e.g . the "cefuroxime-group" and the "cefotaxime-group" have been defined . Based on epidemiologic and comparative in vitro data, the present review offers some guidance where the less expensive cephalosporins of the "cefuroxime-group" may still be clinically useful.

Ter Arkh, 1993, 65(9), 62 - 4
{Infectious endocarditis in middle-aged and elderly patients}; Butkevich OM et al.; The analysis is presented of clinical picture, running, therapy and prognosis of infectious endocarditis in 67 patients over 60 . They appeared to develop progressive cardiac failure, frequent thromboembolism of the cerebral vessels . The disease is often associated with other age-related disorders, proved difficult for differential diagnosis . Elderly patients show resistance to antibacterial therapy more frequently and have worse prognosis for endocarditis outcome.

Ter Arkh, 1993, 65(10), 50 - 5
{Acute pneumonia in patients with multiple primary malignant neoplasms}; Tugova IuE et al.; The authors review 35 cases of acute pneumonia (AP) in 30 patients with multifocal cancer . As a rule, AP was focal, ran a moderate or severe course, arose acutely with high temperature, chill, cough, purulent discharge . Auscultation registered weak vesicular breath, moist rale . Among pathological agents prevailed associations of pneumococci with gram-negative flora . AP resolved for 3-4 weeks in 2/3 of the patients, the rest of them developed lingering disease . From the point of view of antibacterial drugs efficacy, wide-spectrum drugs are preferable.

Probl Tuberk, 1993, (5), 18 - 20
{Chemotherapy of destructive pulmonary tuberculosis with antioxidants and antihypoxic agents}; Savula MM et al.; The trial included 155 patients with destructive pulmonary tuberculosis: 60 on conventional antibacterial therapy (isoniazid, rifampicin, streptomycin), 95 on intensive chemotherapy (isoniazid, rifampicin, streptomycin, pirazinamid or ethambutol, vitamins for initial 2-3 months) . 69 patients from the latter group received adjuvant antioxidants (tocopherol acetate or galascorbin) in combination with one of the antihypoxants (piracetam, calcii pangamas, piriditol) . The intensive chemotherapy promoted a decrease in duration of bacterial discharge, destruction discontimation, cavernous healing, reduced incidence rates of side effects . Metabolic processes characterizing lipid peroxidation and redox improved.

Postgrad Med J, 1993, 69 Suppl 3, S4 - 9
Review presentation on povidone-iodine antisepsis in the oral cavity; Rahn R; Due to the great number of different micro-organisms present, the oral cavity is an important source of infection . Infections caused by these micro-organisms can occur as local infections of the oral mucous membrane, local infections of the soft tissues or the bones following surgical intervention, or endocarditis due to bacteraemia following dental surgery . In the therapy of periodontal diseases, the application of antiseptic solutions is indicated to inhibit or reduce plaque accumulation . Povidone-iodine (PVP-I) solution will reduce inflammation and the progression of periodontal disease . The application of antiseptics in the oral mucous membrane is also indicated to prevent wound infections following surgical intervention in patients with leukaemia, AIDS, immunosuppressant therapy and patients undergoing anti-neoplastic radiation or chemotherapy . Some trials on the antibacterial efficacy of PVP-I in vivo showed reduction factors of log 2-3 . PVP-I may therefore be recommended as an oral antiseptic . The irrigation of the gingival sulcus with an antiseptic solution is a useful complement to antibiotic prophylaxis in patients at risk of bacterial endocarditis . Many trials on the effectiveness of PVP-I on dental extraction bacteraemia have shown a significant benefit in the active group in comparison with the control group.

Agents Actions, 1993, 39 Spec No, C207 - 10
Structural characterization of BPI-modulating 15 kDa proteins from rabbit polymorphonuclear leukocytes: identification of a novel family of leukocyte proteins; Levy O et al.; We have previously described the isolation and initial characterization of 15 kDa protein isoforms (p15s) from rabbit polymorphonuclear leukocytes (PMN) that bind to Escherichia coli and modulate the antibacterial actions of other leukocyte proteins on this gram negative organism . We now report that the p15s differ in primary structure . The cloning and sequencing of two distinct p15 cDNAs from a rabbit bone marrow library reveal that two of the isoforms are closely similar in primary structure differing at only two amino acid positions . The p15 cDNAs encode putative signal sequences suggesting a granule-associated localization for these proteins . Analysis of the derived p15 primary structures reveals homology to two leukocyte proteins: CAP-18, an 18 kD lipopolysaccharide (LPS) binding protein from rabbit PMN and cathelin, an 11 kD cysteine protease inhibitor from porcine leukocytes . This structural similarity suggests the existence of a novel family of low molecular weight leukocyte proteins with potential roles in inflammation.

Korean J Intern Med, 1993 Jan, 8(1), 19 - 24
Antral Helicobacter pylori infection, hypergastrinemia and peptic ulcers: effect of eradicating the organism; Park SM et al.; BACKGROUND: A randomized prospective study on the response of fasting serum gastrin concentrations in peptic ulcer patients was performed in order to test the hypothesis that H . pylori infection in the gastric antrum increases gastrin release, and to examine whether the high fasting serum gastrin concentrations respond to treatment that eradicates H . pylori . METHODS: One hundred and twenty-seven patients with gastric or duodenal ulcer were included in this study . Patients were divided into three groups on the basis of antral H . pylori status and therapeutic modalities . The first group, 58 patients infected by H . pylori, was treated with metronidazole and tripotassium dicitrato bismuthate combined with ranitidine and mylanta . The second group, 40 patients also infected by H . Pylori, was treated with ranitidine and mylanta . The third group, 29 patients, free of H . pylori infection, was designed to evaluate the influence of H2-receptor antagonist on the change of gastrin . When ulcers were completely healed, changes of gastrin concentrations and H . pylori status were re-examined . RESULTS: H . pylori was eradicated in all patients who have received antibacterial therapy in 4 weeks, and serum gastrin concentrations were significantly decreased after eradication of the organism both in gastric and in duodenal ulcer diseases . (Gastric ulcer: 129.3 +/- 47.0 pg/ml before and 63.7 +/- 21.6 pg/ml after treatment . Duodenal ulcer: 108.3 +/- 35.0 pg/ml and 66.5 +/- 21.9 pg/ml, respectively . Total: 112.7 +/- 38.2 pg/ml vs 66.0 +/- 21.6 pg/ml) (p < 0.01) . In contrast, H . pylori-positive patients who have not received antibacterial therapy were still infected at the completion of the study, and serum gastrin concentrations increased even though the difference was not significant . (Gastric ulcer: 118.4 +/- 51.2 pg/ml vs 124.0 +/- 56.5 pg/ml . Duodenal ulcer: 85.4 +/- 35.1 pg/ml vs 104.6 +/- 43.5 . Total: 99.5 +/- 45.3 vs 112.9 +/- 48.7 pg/ml.) (p > 0.05) . None of the patients who were initially H . pylori-negative has been reinfected during the period of the study, and their serum gastrin concentrations were not changed . (Gastric ulcer: 69.8 +/- 38.0 pg/ml . Total: 63.2 +/- 31.1 pg/ml . Duodenal ulcer: 55.1 +/- 17.6 pg/ml vs 55.8 +/- 13.8 pg/ml . Total: 63.2 +/- 31.1 pg/ml vs 63.4 +/- 30.0 pg/ml) . Four- to six-week therapy of H2-receptor antagonist and antacid had no influence on serum gastrin concentrations . CONCLUSIONS: On the basis of the above results, we confirmed that the chronic infection of H . pylori of gastric antrum in peptic ulcer patients causes increased release of serum gastrin, and eradication of the organism results in a significant fall in serum gastrin concentrations.

Akush Ginekol (Mosk), 1993, (5), 18 - 21
{The use of plasmapheresis in the combined treatment of pregnant patients with pyelonephritis}; Neimark AI et al.; The results of pyelonephritis treatment in 48 pregnant patients are analyzed . Twenty-three patients were administered routine antibacterial therapy, in 25 ones plasmapheresis was added to it . Immunity status of all the patients was examined . Antibiotic therapy was conducive to improvement of the patients' status, to a reduction of the renal inflammation severity, though it did not completely eliminate immunodeficiency signs . B lymphocyte and immunoglobulin levels persisted reduced . Plasmapheresis promoted a more swift elimination of clinical and laboratory signs of pyelonephritis and virtually completely liquidated immunodeficiency.

Arch Immunol Ther Exp (Warsz), 1993, 41(2), 137 - 40
Vratizolin in treatment of mouth and ear herpetic infections: comparison with conventional therapy; Rostkowska B et al.; Vratizolin is a new non-steroidal anti-inflammatory drug registered for use on humans in Poland . Published and unpublished data on Vratizolin showed that it has anti-inflammatory, antiviral, antibacterial, antimycotic, analgesic and immunomodulating activities . The purpose of these randomized, parallel-group studies was to compare Vratizolin with other standard drugs, used for the treatment of mouth and ear infections . The study involved 193 patients with recurrent Herpes simplex, Herpes zoster oticus, Stomatitis herpetica and infections of the external ear canal . Vratizolin was used topically, as 3% hydrophilic cream or ointment, four times daily . Standard treatment included zinc ointment, Aphtin (boric acid plus glycerin), Oxycort and Dicortinef . In almost all of the treated patients the efficacy of Vratizolin treatment was superior to the drugs mentioned above . It was assessed by measuring disappearance of both objective (edema, erythema, crusting) and subjective symptoms (pain, burning and itching).

Turk J Pediatr, 1993 Jan-Mar, 35(1), 65 - 7
Cardiac arrest: an unusual side-effect of intravenous ornidazole; Ozen H et al.; Nitroimidazoles have been used alone or in combination with other antibacterial agents in the treatment of brain abscess . They are associated with certain adverse reactions related primarily to the gastrointestinal tract and central nervous system . But, as far as we know, cardiac arrest due to ornidazole has not been reported in the literature . In this study, we presented a case in which cardiac arrest occurred as an unusual side-effect of intravenous ornidazole administered to a ten-year-old girl suffering from brain abscess.

Med Dosw Mikrobiol, 1993, 45(1), 11 - 4
{Evaluation of drug sensitivity and biochemical properties of coagulase-negative S . aureus strains isolated from clinical specimens}; Szymanowska A et al.; 20-25% of strains isolated in our hospital in 1991 from clinical specimens and identified as S . aureus were coagulase-negative . These strains were characterized in respect of biochemical properties and resistance to antibacterial drugs . It was shown that the investigated group of strains displayed high drug resistance and particularly high percent of strains were resistant to methicillin (60%) . 100% strains were resistant to penicillin and tetracyclines and most of them were resistant to aminocyclitol antibiotics . Coagulase-negative strains, in comparison with coagulase-positive, less frequently produced hemolysins and more frequently staphylokinase.

Vet Res, 1993, 24(4), 316 - 26
{Antibacterial sulfonamides, antiparasitic and antifungal derivatives of imidazole: evaluation of their antithyroid effects in the rat}; Comby F et al.; Antithyroid action of some antibacterial, antiparasitic or antifungal agents, was studied by 2 in vitro and 3 in vivo experimentations in the rat . These drugs can upset thyroid hormone synthesis by forming a molecular complex with iodine, and/or by inhibiting thyroid peroxidase activity . Rats treated with these drugs showed an hypothyroidism, demonstrated both by a decrease in T4 concentration and an hyperactivity of thyroid gland by positive feed-back, whose consequence was the presence of cylindrical cells . We noticed this iatrogenic hypothyroidism with all the drugs experimented, by an increase in thyroid gland weight . But the increase of rats body weight, which should have appeared, was not shown . The use of anabolic steroid is now forbidden, therefore, such drugs could be used for breeding animals, in order to gain body weight . Detection of use of these drugs in breeding, to obtain this side effect, should be advised.

Arch Toxicol, 1993, 67(6), 411 - 5
Chondrotoxicity of quinolones in vivo and in vitro; Hildebrand H et al.; Chondrotoxicity is a rare toxicological finding which is observed in dogs after administration of quinolone antibacterials . To study this effect chondrocytes from articular cartilage of dogs were isolated, and incubated with quinolone derivatives . The effects on cell viability, mitochondrial dehydrogenase, and proteoglycan synthesis were determined . These results were compared with in vivo findings in dogs treated with these quinolones . It was concluded that inhibition of mitochondrial dehydrogenase activity and of proteoglycan synthesis are major reasons for cartilage damage . Therefore this in vitro model is capable of identifying strongly arthropathogenic quinolones without the need of performing animal studies.

Ter Arkh, 1993, 65(7), 67 - 70
{The neutrophil antibacterial function of patients with chronic bronchitis . Its immune correction by using inflammatory cytokines and allogeneic lymphocytes in vitro}; Pechkovskii DV et al.; In patients with acute and chronic bronchitis decreased neutrophil phagocytic, induced O2-dependent metabolic, bactericidal activity and the content of lysosomal cationic proteins, increased spontaneous O2-dependent metabolic activity were revealed . The most pronounced neutrophil functional disorders were detected in patients with chronic obstructive bronchitis (COB) . The use of human immunoregulatory recombinant cytokines (interleukin-1 beta, interferon-gamma, tumor necrosis factor alpha) failed to augment in vitro suppressed neutrophil antibacterial (phagocytic) activity in patients with COB . These patient's neutrophil antibacterial activity restored in vitro in the presence of allogeneic (nonactivated or interleukin-2-activated) lymphocytes . The data obtained provide evidence for healthy donor's lymphocytes use in immunocorrection of patients with chronic bronchitis.

Clin Ther, 1993, 15 Suppl B, 49 - 57
Lansoprazole and Helicobacter pylori infection; Pallone F et al.; Helicobacter pylori-associated gastritis is present in virtually all patients with duodenal ulcer (DU) . Eradication of H pylori is associated with a highly significant decline in the recurrence rates of DU, indicating that treatments aimed at eradicating H pylori are mandatory in these patients . The novel proton pump inhibitor lansoprazole exhibits a potent antiulcer effect and, in vitro, a direct antibacterial effect against H pylori . Conflicting data have been reported on the question of whether lansoprazole is bactericidal against H pylori in vivo when administered alone . The aim of this double-blind trial was to address this issue further by comparing the effects of two different 4-week regimens (lansoprazole alone or in combination with amoxicillin) on H pylori infection in patients with DU . Patients were assessed before and after the 4-week treatment and 3 months after stopping the study medication . The ulcer healing rates at 4 weeks were similar for the two treatments while there was a trend for higher recurrence rates at 4 months in patients receiving lansoprazole alone . The frequency of high-grade H pylori infection was significantly lower in the lansoprazole and amoxicillin group both at 4 weeks (84% clearing) and 4 months . After 4 weeks of treatment there were no patients with residual H pylori-positive active antral gastritis in the lansoprazole and amoxicillin group compared with 25% in the lansoprazole alone group . Neither treatment significantly affected the IgG antibody response to H pylori either at the circulatory or the mucosal level . In contrast, the mucosal H pylori-specific IgA response was significantly enhanced after 4 weeks and more markedly after treatment with lansoprazole.(ABSTRACT TRUNCATED AT 250 WORDS)

Ther Hung, 1993, 41(3), 111 - 3
Possible use of Betadine in HIV-positive patients; Miskovits E et al.; The results of Betadine treatment obtained in the course of a one-year period proved the usefulness of the bacteriostatic and bactericidal product as a disinfectant of the skin and mucosa in immuno-deficiency diseases, in our cases in AIDS (but supposedly in other similar diseases as well) . In these diseases this new therapeutic means does supply a need . The solution was successfully used in patients in whom superficial decontamination is of high importance and whose cutaneous and mucosal infections had raised therapeutic problems for years . Side-effects were not observed . The product could be easily applied . If the germ count of the atrophying pathogen is not very high and the lesion is due supposedly to mixed infection, the product will be effective even in monotherapy . Similarly, in mild mycotic infections systemic therapy could be avoided . In cases of purulent alterations the solution is successfully applied as an adjuvant to antibacterial treatment and its continuous use prevents early recurrence . The long-term use of the product did not cause side-effects, irritation of the skin or the mucosa.

Acta Microbiol Hung, 1993, 40(3), 201 - 16
Carriage, transfer and interaction of oral viruses and bacteria; Ongradi J et al.; Carriage of antigens and infectious herpes simplex virus type 1 (HSV-1) and human adenovirus type 1 (Ad-1) by salivary leukocytes was compared with the antibacterial activity of oral polymorphonuclear leukocytes (PMNL) and with the spectrum of oral bacterial and fungal flora . Risk of iatrogenic infections by microbes was assessed by detecting these viruses and microbes after disinfecting dental instruments . The results indicate carriage of antigens and infectious viruses in each age group between 6 and 60 years . Phagocytic activity by PMNL of virus carrier persons was found to be decreased as compared to virus-free subjects . The species number and survival after disinfection of oral bacteria and fungi were significantly higher in virus carrier persons . Infectious viruses were also obtained after disinfecting instruments used in their dental treatment . It is concluded that, virus infection of immune cells can contribute to the oral suppression of phagocytosis by PMNL . Intracellular viruses hidden from disinfectants can also result in infection of other subjects, especially if contemporary immunosuppression exists.

Drugs Exp Clin Res, 1993, 19(5), 189 - 95
A major role for cytochrome P450TB (CYP2C subfamily) in the actions of non-steroidal antiinflammatory drugs; Leemann TD et al.; Most non-steroidal antiinflammatory drugs (NSAIDs) are extensively metabolized by liver oxidation with broad interindividual variability, but little is known about the nature of the enzyme(s) catalysing these reactions . The role of specific cytochrome P450 isozymes in the formation of the major oxidized metabolites of phenylacetic acid (diclofenac), propionic acid (ibuprofen), fenamate (mefenamic acid) and oxicam (piroxicam and tenoxicam) derivatives was studied in human liver microsomes using mostly selective inhibition by known substrates and inhibitors of specific cytochrome P450 monooxygenases . A common isozyme (P450TB, CYP2C subfamily) controls the major elimination pathways of these NSAIDs . The authors have also determined, in two in vitro models of P450TB activity, the affinity for this isozyme of other NSAIDs (acetylsalicylic acid, indomethacin, pirprofen) . The NSAIDs tested displayed a high affinity (5-500 microM): diclofenac approximately mefenamic acid > ibuprofen approximately indomethacin approximately piroxicam approximately tenoxicam > acetylsalicylic acid approximately pirprofen . Cytochrome P450TB therefore plays a key role in the oxidation by human liver of major NSAIDs from various chemical classes . Inhibition data and chemical structure similarities suggest that many other NSAIDs may be substrates of this isozyme as well . P450TB appears to be a common site both for the control of interindividual differences in the capacity to oxidize major NSAIDs and for interactions involving NSAIDs as well as other known substrates (oral anticoagulants, hypoglycaemic sulfonylureas, phenytoin) or inhibitors (antifungals, antibacterial sulfonamides, calcium channel blockers) of P450TB . Consequently this P450 isozyme is likely to be a major determinant of NSAIDs action.

Klin Khir, 1993, (9-10), 37 - 40
{Treatment of purulent and necrotic lesions of the lower extremities in patients with diabetes mellitus}; Ohonovsky? VK et al.; The results of complex treatment of 172 diabetic patients with purulent-inflammatory lesions of the lower extremities, using intensive purposeful antibacterial and desintoxicative therapy, timely and sufficient opening of purulent foci as well as administration of desagregants, stimulators of reparative processes, anabolic hormones, vitamins etc., are presented . Correction of carbohydrate metabolism was performed by means of insulin therapy according to the optimized scheme . Use of UV irradiation of the blood of the patients and local antiinflammatory roentgenotherapy contributed to increase in effectiveness of treatment . Incidence of amputation of an extremity at a level of a thigh was 20.2%, lethality-8.1%.

Eur J Clin Pharmacol, 1993, 45(6), 529 - 34
Plasma levels of piperacillin and vancomycin used as prophylaxis in liver transplant patients; Dupon M et al.; The pharmacokinetics of piperacillin and vancomycin used intravenously as antibioprophylaxis were measured in the plasma and bile during orthotopic liver transplantation . Piperacillin (4 g and then 2 g every 4 h) and vancomycin (1 g and then 0.5 g every 6 h) were infused in 10 patients . During vascular clamping without venovenous bypass, clearance of both antibiotics decreased in relation to renal insufficiency . During the surgical procedure, volume of distribution of both drugs increased because of fluid redistribution . The peaks of piperacillin after first, second and third administrations were respectively 314, 265 and 210 mg.l-1, while trough levels were 46.5, 55.2 and 54.5 mg.l-1 . The peaks of vancomycin were 54.4, 49.6 and 40.9 mg.l-1, while first and second trough levels were 9.5 and 12 mg.l-1 . These plasma concentrations were quite similar to levels reported in healthy subjects despite large blood loss and fluid replacement . However, piperacillin trough concentrations (< 64 mg/l) were too low in relation to its concentration-dependent antibacterial activity and vancomycin peak concentrations (> or = 40 mg/l) were slightly too high in relation to its toxicity.

Rev Med Chir Soc Med Nat Iasi, 1993 Jan-Mar, 97(1), 433 - 7
{The antibacterial action of new hydrazide derivatives}; Ciugureanu C et al.; New derivatives of 4-aminobenzoic and 4-chlorine-2-hydroxybenzoic acids hydrazides were synthesized by the condensation reaction of these hydrazides with aldehydes and ketones, derivatives containing in their molecule azometine and hydrazone groups . The obtained products are potentially bioactive . The study of their "in vitro" biological activity was performed on some pathogenic germs, both gram-positive and gram-negative . The results show that the tested substances are more active towards the gram-positive germs.

Dig Dis Sci, 1993 Jan, 38(1), 123 - 8
Treatment of Helicobacter pylori-associated gastroduodenal disease in children . Clinical evaluation of antisecretory vs antibacterial therapy; Rosioru C et al.; The charts of 54 children diagnosed with antral H . pylori were reviewed, to establish the incidence of gastroduodenal inflammation and compare therapeutic efficacies of antisecretory vs . antibacterial therapy . Histology demonstrated normal mucosa in three cases (6%) and gastric/duodenal inflammation (> or = Whitehead grade 3) in 51 biopsies (94%) . 23/43 children (53%) initially responded to H2-blockers; however, by 10 mo, 13 had relapsed clinically . All of these patients subsequently responded to amoxicillin plus bismuth subsalicylate . Of the 20 children who failed to enter remission after an initial course of H2-blockers, all became symptom-free after treatment with amoxicillin/bismuth . Compared to antisecretory agents, antibacterial treatment induced clinical remission in 11/11 patients (p < 0.001), who remained symptom-free for 10 +/- 0.2 mo . Clinical remissions were maintained in significantly more patients following amoxicillin/bismuth vs . H2-blockers (44/54 vs . 10/43 courses, p < 0.001); and, the cumulative probability of remaining asymptomatic was significantly greater in the antibiotic group (p < 0.001) . These data suggest that gastric colonization by H . pylori is highly predictive of mucosal pathology in children . Initial therapy should be directed toward achieving bacterial eradication, as opposed to gastric acid suppression.

Rev Int Trach Pathol Ocul Trop Subtrop Sante Publique, 1993, 70, 171 - 7
{Antibioprophylaxis and itinerant ambulatory surgery in the milieu of endemic trachoma}; Cherkaoui O et al.; Between 1987 to 1992, 3,309 eyes had been operated on during the seventeen missions realized in Morrocco, by the Morroccan Itinerant Ophthalmologist Association . To prevent postoperative infectious endophthalmitis, asepsis was rigorous and local antibiotics prophylaxis were administered preoperatively, during surgery and postoperatively . Ophthalmic solutions (gentamicin, norfloxacin, or ofloxacin) were used . Six (6) eyes in our study developed infectious endophthalmitis (1.8) . The fluoroquinolones are a new class of antibacterial agents with considerable potential in the treatment of ophthalmic infections . A systematic antibioprophylaxis with fluoroquinolones, is licit in itinerant surgery.

Yao Xue Xue Bao, 1993, 28(11), 865 - 9
{Synthesis and antibacterial activities of 1-amino-6-fluoro-1,4-dihydro-4-oxo-7-(substituted) piperazinyl-3-quinolinecarboxylic acids and their derivatives}; Xin T et al.; The title compounds 6-24 were obtained by the reaction of 5 with corresponding benzaldehydes . 5 was prepared with ethyl 7-chloro-6-fluoro-1,4-dihydro-4-oxo-3- quinolinecarboxylate by hydrolysis, amination and condensation with piperazine . Anti-bacterial activities of 5-24 were tested in vitro.

Drugs, 1993, 45 Suppl 3, 1 - 7
The future of the quinolones; Andriole VT; This review attempts to predict the future of the newer fluoroquinolones by examining what we have learned about this class of compounds during the past decade, as well as what we are currently learning from research and developmental efforts . The molecular mechanism of action of these compounds provides the potential for use in clinical medicine in areas other than their role as antibacterial agents . The newer fluoroquinolones that are currently available and those that have been introduced into the pipeline are categorised by their current stage of development . Also listed are those compounds that have been withdrawn from further investigation . Office practice physicians consider the oral fluoroquinolones to be very effective therapeutic agents for many of their patients . Thus, the future of the fluoroquinolones looks promising because of their unique mechanism of action, the possibility of developing novel and improved compounds in this class, and the acceptance of these compounds as effective therapeutic agents by clinicians.

J Immunol, 1993 Jan 1, 150(1), 253 - 63
Human granulocytes express a 55-kDa lipopolysaccharide-binding protein on the cell surface that is identical to the bactericidal/permeability-increasing protein; Weersink AJ et al.; Several LPS-binding proteins have been identified on the surface of human granulocytes (polymorphonuclear leukocyte (PMN)) . We describe a plasma-membrane associated ca . 55-kDa LPS-binding protein of human PMN that is indistinguishable from the bactericidal/permeability-increasing protein (BPI) . To detect LPS-binding proteins on the cell surface, PMN were biotinylated before detergent solubilization and incubation with LPS-coated beads . Several biotinylated proteins bound to LPS-coated beads but not to uncoated beads and were characterized after elution with detergent by SDS-PAGE and western blotting using streptavidin-horseradish peroxidase . The spectrum of biotinylated proteins binding to and eluting from LPS-coated beads increased as the number of beads incubated with PMN lysate increased . However, at all concentrations of beads a 55-kDa protein was a dominant component of the eluate . Binding of the 55-kDa protein to LPS-coated beads was inhibited by lipid A, and both homologous and heterologous LPS, but not by peptidoglycan . Similar amounts of biotinylated 55-kDa LPS-binding protein were detected on PMN from patients with paroxysmal nocturnal hemoglobinuria who lacked membrane bound CD14, a known ca . 55-kDa plasma membrane-associated LPS-binding protein, indicating that the recovered biotinylated protein is not CD14 . Several pieces of evidence, however, do indicate that the 55-kDa surface protein is BPI: 1) flow cytometry of PMN after labeling with rabbit anti-BPI serum and FITC-labeled goat anti-rabbit IgG revealed immunoreactive surface molecules on resting PMN and, in increased amounts, on PMN stimulated with FMLP or TNF; 2) This antiserum specifically and quantitatively inhibited binding of the biotinylated 55-kDa species to LPS-coated beads; 3) both BPI and the 55-kDa protein migrated as a doublet during SDS-PAGE and were both converted to single migrated species after N-glycosidase F treatment; 4) chemical cleavage of the biotinylated protein and native BPI with N-chlorosuccinimide yielded the same fragments . Thus, we have positively identified BPI as a LPS-binding protein on the surface of PMN . The role of this potent antibacterial, endotoxin neutralizing protein on the surface of PMN remains to be established.

Drugs, 1993, 46 Suppl 1, 107 - 10
Treatment of upper airways inflammation with nimesulide; Bellussi L et al.; Nimesulide treatment for 7 to 10 days is shown to be effective in controlling the inflammatory process in upper airways disorders such as rhinitis, rhinosinusitis, rhinopharyngitis and tubaritis, and in middle ear disorder (secretory otitis media) . A concomitant antibacterial is considered necessary in cases involving infection, in order to retain the improvements in mucociliary transport obtained with anti-inflammatory treatment . Nimesulide is also shown to be effective when given in combination with the mucolytic drug ambroxol.

FEMS Microbiol Lett, 1992 Dec 15, 79(1-3), 293 - 7
Inhibitors of lipopolysaccharide biosynthesis impair the virulence potential of Escherichia coli; Hammond SM; Inhibition of 3-deoxy-manno-octulosonate cytidylytransferase (CMP-KDO transferase; EC 2.7.7.38) by 8-amino-2,6-anhydro-3,8-dideoxy-D-glycero-D-talo-octonic acid (NH2dKDO) halts the growth of Gram-negative bacteria by depriving the cells of the 3-deoxy-D-manno-2-octulosonate required for the biosynthesis of the core region of the lipopolysaccharide components of the outer membrane . Low levels of this inhibitor increase the vulnerability of Escherichia coli to hydrophobic antibiotics, detergents, the complement-mediated antibacterial activity of serum, phagocytosis, and enhance the rate at which bacteria are cleared from the mouse bloodstream.

J Med Chem, 1992 Dec 11, 35(25), 4727 - 38
Studies on pyridonecarboxylic acids . 1 . Synthesis and antibacterial evaluation of 7-substituted-6-halo-4-oxo-4H-{1,3}thiazeto{3,2-a}quinoline-3- carboxylic acids; Segawa J et al.; A series of {1,3}thiazeto{3,2-a}quinoline-3-carboxylic acids and their esters were prepared and evaluated for antibacterial activity . The derivatives with a hydrogen or methyl group at C-1, fluorine at C-6, and piperazinyl or 4-methyl-1-piperazinyl group at C-7 showed superior in vitro antibacterial activity, and the derivatives with 4-methyl-1-piperazinyl group at C-7 had potent in vivo activity . Compound 29a (NM394) showed excellent in vitro antibacterial activity and low toxicity but poor absorption from the gastrointestinal tract . Compound 29ee (NM441), an N-{(5-methyl-2-oxo-1,3-dioxol-4-yl)methyl} derivative of 29a, was found to possess a favorable pharmacokinetic profile and oral activity superior to that of ciprofloxacin in experimental animals.

Schweiz Med Wochenschr, 1992 Dec 5, 122(49), 1897 - 9
{The biotransformation of NSAIDs: a common elimination site and drug interactions}; Leemann T et al.; Many NSAIDs are eliminated predominantly through hepatic biotransformation in man . We have studied, in human hepatic microsomes, the role of specific cytochrome P450 isozymes in the formation of the major metabolites of oxicam (piroxicam and tenoxicam), phenylacetic (diclofenac) and propionic acid (ibuprofen) derivatives . A common isozyme (P450TB, CYP2C subfamily) controls the major elimination pathway of these NSAIDs . We have also determined, in two in vitro models of P450TB, the affinity for this isozyme of NSAIDs from other chemical classes (acetylsalicylic acid, mefenamic acid and indomethacin) . All NSAIDs tested displayed a high affinity (3-300 microM) for cytochrome P450TB . Cytochrome P450TB plays a major role in the elimination of several NSAIDs with different chemical structures . NSAIDs are substrates as well as potential inhibitors of cytochrome P450TB . Their elimination can therefore be reduced by concomitant administration of known inhibitors of P450TB (antifungals, antibacterial sulfonamides, calcium channel blockers).

J Antibiot (Tokyo), 1992 Dec, 45(12), 1930 - 8
Synthesis and activity of 3-(isoxazolin-5-yl)- and 3-(isoxazol-4-yl)cephalosporins; Koyama Y et al.; The 1,3-dipolar cycloaddition of nitrile oxide with 3-vinylcephalosporin provided diastereomeric isomers of 3-(isoxazolin-5-yl)cephalosporin . Cycloaddition of nitrile oxide with 3-(dimethylamino-vinyl)cephalosporin gave 3-(isoxazol-4-yl)cephalosporin . These semisynthetic cephalosporins with an aminothiazole in the C-7 side chain showed moderate antibacterial activities.

Oral Surg Oral Med Oral Pathol, 1992 Dec, 74(6), 742 - 8
Salivary hypofunction in patients with familial amyloidotic polyneuropathy; Johansson I et al.; Patients who suffer from familial amyloidotic polyneuropathy frequently complain of mouth dryness and an increased need for dental treatment . The aim of the present investigation was to study saliva secretion rate and composition and other factors related to the risk of dental caries in patients with familial amyloidotic polyneuropathy . Thirty patients with familial amyloidotic polyneuropathy volunteered for the study and were compared with a matched control group . Samples of unstimulated and stimulated whole saliva were collected in a standardized manner . The secretion rates were calculated, and the concentrations of electrolytes, glycoprotein markers, and proteins with antibacterial properties were analyzed . Dental caries and variables related to the risk of dental caries were also scored . The results show that familial amyloidotic polyneuropathy patients frequently have a decreased rate of saliva secretion and that the degree of salivary hypofunction is positively correlated to the progress of familial amyloidotic polyneuropathy . Forty-three percent of the familial amyloidotic polyneuropathy patients in this study had no detectable secretion of unstimulated saliva . A low secretion rate of stimulated saliva (< 0.7 ml/min) was found in 33% of the patients . The concentrations of salivary protein, amylase, lysozyme, salivary peroxidase, secretory IgA, hexosamines, sialic acid, fucose, phosphate, potassium, and the degree of protein glycosylation were higher in the familial amyloidotic polyneuropathy patients than in the control patients . We conclude that patients with familial amyloidotic polyneuropathy have a reduced saliva secretion and are subsequently at risk for increased development of dental caries.

Am J Vet Res, 1992 Dec, 53(12), 2311 - 4
Effects of endotoxin-induced mastitis on the pharmacokinetic properties of aditoprim in dairy cows; Lohuis JA et al.; Plasma disposition of aditoprim, a new dihydrofolate reductase inhibitor, was studied in healthy cows and cows with endotoxin-induced mastitis . A single dose of 5 mg of aditoprim/kg of body weight was administered IV to 5 healthy cows and to the same cows 3 weeks later at 2 hours after intramammary infusion of 0.1 mg of endotoxin into the rear quarters . Mastitis developed in all endotoxin-infused quarters and cows had systemic signs of disease (fever, tachycardia, depression) from 2 to 10 hours after infusion of endotoxin . Pharmacokinetic characteristics of aditoprim in healthy cows were a large volume of distribution (6.28 L/kg), a systemic clearance of 0.82 L/h/kg, and an elimination half-life of 7.26 hours . In cows with mastitis, plasma concentrations of aditoprim were lower between 5 and 26 hours after injection . The systemic clearance (1.00 L/h/kg) and the volume of distribution (12.25 L/kg) were significantly higher in cows with mastitis, but elimination half-life was not significantly different . The lower plasma concentrations of aditoprim between 5 and 26 hours after injection in cows with mastitis are explained by fluid compartment shifts and/or blood flow changes induced by mastitis, although increased elimination of aditoprim in cows with mastitis cannot completely be ruled out . The antibacterial activity of aditoprim is nearly the same as that of trimethoprim . The longer elimination half-life time of aditoprim, however, indicates that it may have a practical pharmacotherapeutic advantage over trimethoprim.

J Pharmacol Exp Ther, 1992 Dec, 263(3), 1464 - 70
Determinants of the in vitro interaction of polyaspartic acid and aminoglycoside antibiotics; Kohlhepp SJ et al.; The in vitro interaction of polyaspartic acid (PAA) with aminoglycosides was evaluated using double diffusion in agar, dialysis chambers and changes in the optical density of test solutions . The results document a reversible, presumably electrostatic interaction that is optimized at a pH of approximately 5.0, by the absence of proteins over 800 Da, and at a 20:1 or 10:1 molar ratio of aminoglycoside to PAA . The PAA-aminoglycoside complex lost antibacterial activity and the ability to inhibit pronase E enzymatic activity . These results allow generation of a hypothesis as to the mechanism whereby PAA prevents aminoglycoside experimental nephrotoxicity.

J Trop Med Hyg, 1992 Dec, 95(6), 397 - 403
Antibacterial agents for wounds and burns in the developing world . Report on a workshop; Ryan TJ; Publications on the use of antibacterial agents for wounds and burns in the developing world continue to emphasize the value of antiseptics such as Eusol and gentian violet . In the developed world these agents have been mostly discredited . A workshop organized by the European Society for Tissue Repair concluded that clearer instructions about the role of antibacterial agents in the management of wounds and burns could clarify appropriate usage . The report considers the factors contributing to infection and rationalizes the use of disinfectants, antiseptics and antibiotics, especially in the developing world.

Antibiot Khimioter, 1992 Dec, 37(12), 19 - 21
{Production of griseoviridin and etamycin by the new culture, Streptomyces albolongus}; Terekhova LP et al.; An actinomycete strain designated as 4297 was isolated from a soil sample collected near Moscow . The strain produced a complex of two antibiotics . One of them had a broad antibacterial spectrum and, in terms of its physicochemical properties and X-ray structural evidence, was identified with griseoviridin . The other was active against gram-positive bacteria and, by its chromatographic comparison with an authentic sample, mass spectroscopic determination of the molecular weight and UV spectra, was identified with etamycin . The strain 4297 differed from the described cultures producing griseoviridin and etamycin . By the taxonomic features it was classified as belonging to Streptomyces albolongus.

Farmaco, 1992 Dec, 47(12), 1543 - 54
Antifungal and antibacterial activity of 2-acetylpyridine-(4-phenylthiosemicarbazone) and its metal (II) complexes; Offiong OE et al.; 2-Acetylpyridine-(4-phenylthiosemicarbazone) and its metal (II) complexes have been synthesized and characterized by chemical and spectral methods . They were studied for their antibacterial and antifungal activities in vitro . The ligand and its metal (II) complexes exibited significant activity against a wide spectrum of bacteria and fungi.

J Immunol Methods, 1992 Nov 25, 156(1), 85 - 99
Sn-chlorin e6 antibacterial immunoconjugates . An in vitro and in vivo analysis; Lu XM et al.; Monoclonal antibody-Sn-chlorin e6 immunoconjugates were prepared by the site-selective covalent modification of the monoclonal oligosaccharide moiety . By carefully controlling the reaction conditions and introducing triethanolamine groups as axial ligands of the Sn moiety, conjugates with in vivo biodistribution properties similar to underivatized IgG were prepared . By varying the reaction conditions, conjugates were reproducibly prepared with a range of photosensitizer to mAb molar ratios from 1.6 to 10 . Based on a competitive inhibition radioimmunoassay, conjugates prepared by this method showed selectivity and binding affinity comparable to the unmodified antibody . The immunoconjugates had only slightly lower singlet oxygen yields than that observed with the Sn-chlorin e6 precursor indicating that negligible aggregation or structural modification of the chromophores occurred during the synthesis process . In vitro cell killing experiments demonstrated that all conjugates possessed significant cytotoxic activity . Biodistribution studies in mice showed that conjugates prepared with axial ligands had significant serum retention 24 h after injection while conjugates prepared without the triethanolamine ligand were much more rapidly cleared . In vivo specificity was demonstrated using rats infected with Fisher immunotype I P . aeruginosa at a site in the left posterior thigh muscle . Target to background ratios exceeded 60 at 120 h after conjugate injection of the specific immunoconjugate, compared to a ratio of only 6 for a non-specific mouse IgG conjugate . Biodistribution patterns at 120 h post injection indicate that the conjugates were both biologically active and structurally intact.

Biochem J, 1992 Nov 15, 288 ( Pt 1), 281 - 4
The fate of the prosegment in the acute-phase and programmed synthesis of sapecin, an antibacterial peptide of the flesh fly (Sarcophaga peregrina); Homma K et al.; The nucleotide sequence of sapecin cDNA suggested that this antibacterial peptide of the flesh fly (Sarcophaga peregrina) is produced from preprosapecin by post-translational processing . We examined the production of sapecin and its prosegment by radioimmunoassay under two different physiological conditions in which its gene is activated, assuming that the prosegment has some biological role . Results suggested that the prosegment is degraded selectively during production of sapecin . We also found that imaginal discs synthesize sapecin when cultured in the presence of 20-hydroxyecdysone.

Arzneimittelforschung, 1992 Nov, 42(11), 1350 - 3
Potentially active hypoglycemic agents from N1-nicotinoyl-2-pyrazolin-5-one derivatives and their N1-(oxynicotinoyl) analogues; Girges MM et al.; Several ethyl 2,3-dioxohexanoate 2-arylhydrazone derivatives were obtained via coupling of the appropriate diazonium chlorides with ethyl butanoylacetate . Acetic acid-mediated cyclization of these products with N1-nicotinoyl and/or N1-(oxynicotinoyl)hydrazine derivatives gave a new series of 4-arylhydrazono-3-(n-propyl)-N1-nicotinoyl-2-pyrazolin-5-one s (Va-h) as well as their N1-(oxynicotinoyl) analogues (VIa-h) . The structure of the prepared compounds was confirmed on the basis of elemental and spectral data . The hypoglycemic effect, antibacterial activity and toxicity of these agents were evaluated and discussed.

Antimicrob Agents Chemother, 1992 Nov, 36(11), 2439 - 43
Comparison of the antibacterial effects of cefepime and ceftazidime against Escherichia coli in vitro and in vivo; Mattie H et al.; The efficacies of cefepime and ceftazidime in an experimental Escherichia coli infection in granulocytopenic mice were related to their in vitro activities and their pharmacokinetic profiles . Cefepime had a higher intrinsic activity in vitro than ceftazidime, and it had a different pharmacokinetic profile, resulting in higher peak concentrations in plasma and a longer elimination half-life . To predict the antibacterial efficacy in vivo on the basis of in vitro activity and pharmacokinetics, we applied a mathematical model in which the in vitro effect is expressed as the difference in growth rate between control cultures and cultures grown in the presence of the antibiotic (ER), whereas the in vivo effect is given by the difference in the number of CFU between controls and antibiotic-treated animals (EN) . The integral of ER over time, called ERt, was calculated by using in vivo concentrations . A significant linear relationship was found between EN and ERt for different doses at various times up to 4 h after administration, although the slope of this relationship was slightly but significantly less for cefepime (0.44) than for ceftazidime (0.59).

Acta Pharm Hung, 1992 Nov, 62(6), 302 - 9
{Formulation and in vitro investigation of antibacterial vaginal suppositories . Part 2 . In vitro membrane diffusion and microbiologic studies}; Tarine Gombkoto Z et al.; After the physical parameters had been determined, the in vitro drug liberation from vaginal suppositories containing 100 mg of antibacterial agent (sulphadimine, chloramphenicol, gentamicin-sulphate) was studied by membrane diffusion and microbiological methods . Among the vehicles available in Hungary the hydrophylic Massa macrogoli was found to be the best for this purpose . Among the lipophilic bases the in vitro drug liberation of the French Suppocire NA product was significantly better (p < 0.05) compared to the other lipophilic bases . This vehicle is recommended by the authors for the topical treatment of vaginitis, as these suppositories have the further advantage that they can easily be produced on a magistral, galenical or industrial scale as well . In the first part of the publication the formulation and some important physical parameters of lipophilic and hydrophilic antibacterial suppositories for vaginal use were described . In the present paper the drug liberation ability of the compositions with proper physical parameters was studied . The published results were obtained from measurements performed 1 week after formulation.

Acta Pharm Hung, 1992 Nov, 62(6), 295 - 301
{Formulation and in vitro investigation of antibacterial vaginal suppositories . Part 1 . Considerations in selecting the vehicle . Methods and results of the physical examination}; Tarine Gombkoto Z et al.; Vaginal suppositories frequently used in gynaecological therapy were studied . Several antibacterial pharmacons are used for the topical treatment of vaginitis of various origins . However, the choice of the vaginal suppository base was often considered to be of minor importance for a long time . In view of the fact that the liberation of the given active substance and the subsequent therapeutic effect may be improved or inhibited by the vehicle, their aim was to find the optimal suppository base for vaginal suppositories containing sulphadimidine, chloramphenicol and gentamicin-sulphate by means of in vitro experiments . On the basis of breaking hardness, disintegration time and spreading properties the French Suppocire NA product, and compositions of macrogols with lower molecular weight proved to be the best lipophilic and hydrophilic bases respectively.

Ital J Gastroenterol, 1992 Nov-Dec, 24(9 Suppl 2), 17 - 8
Antibacterial drugs in Crohn's disease; Pallone F et al.; The evidence of a beneficial role of antibacterial drugs in Crohn's disease is largely empirical . Data accumulate to show that these drugs may well be used as an adjunctive therapy to oral anti-inflammatory drugs . Circumstantial evidence has also been provided that antibacterial drugs are effective in relieving symptoms related to bacterial overgrowth and when used for specific indications such as perianal lesions.

Arch Pharm (Weinheim), 1992 Nov, 325(11), 687 - 94
Antibacterial and antifungal agents . XV . Synthesis and antifungal activity of structural analogues of bifonazole and ketoconazole; Stefancich G et al.; The synthesis and antifungal activities of the cis- and trans-1-acetyl-4-{4-{{2-(1,1'-biphenyl-4-yl)-2-(1H-imidazol-1-ylmethy l)- 1,3-dioxolan-4-yl}-methoxy}phenyl)piperazines 3 and 4 are reported . Stereochemical assignments to diastereomeric pairs of cis/trans isomers were made on the basis of 1H- and 13C-NMR data . Among test derivatives the best activity was shown by the benzoyl esters of the cis- and trans-{2-(1,1'-biphenyl-4-yl)-2-(1H-imidazol-1-ylmethyl)-1,3-di oxolan-4- yl}methanols 9 and 10.

Int J Pept Protein Res, 1992 Nov, 40(5), 429 - 36
Antibacterial peptides designed as analogs or hybrids of cecropins and melittin; Wade D et al.; Eight new analogs of cecropin A, two new analogs of melittin and 30 hybrid peptides containing sequences from cecropins and melittin have been synthesized . The lengths of the peptides have varied from 37 residues (the length of cecropin A) to 18 residues . The peptides have been assayed for lysis of sheep red blood cells and for antibacterial activity against two Gram negative and three Gram positive bacteria . The best analogs of cecropin A maintained the anti-Escherichia coli activity of the parental peptide, and were not lytic for red blood cells . Melittin and its replacement analogs were all lytic for red blood cells, but an analog with transposed segments was not . Several of the hybrid peptides were found to be both non-hemolytic and highly active against all test bacteria . The data were used to define the structural requirements for antibacterial activity.

Pneumologie, 1992 Nov, 46(11), 573 - 5
{Modification of pediatric lung function measurement by antibacterial filters}; Gruper 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.

Eur J Biochem, 1992 Nov 1, 209(3), 977 - 84
A novel insect defensin mediates the inducible antibacterial activity in larvae of the dragonfly Aeschna cyanea (Paleoptera, Odonata); Bulet P et al.; The injection of low doses of bacteria into the aquatic larvae of dragonflies (Aeschna cyanea, Odonata, Paleoptera) induces the appearance in their hemolymph of a potent antibacterial activity . We have isolated a 38-residue peptide from this hemolymph which is strongly active against Gram-positive bacteria and also shows activity against one of the Gram-negative bacteria which was tested . The peptide is a novel member of the insect defensin family of inducible antibacterial peptides, which had so far only been reported from the higher insect orders believed to have evolved 100 million years after the Paleoptera . Aeschna defensin is more potent than defensin from the dipteran Phormia, from which its structure differs in several interesting aspects, which are discussed in the paper.

Dig Dis Sci, 1992 Nov, 37(11), 1691 - 3
Penetration of ceftriaxone and cefoperazone into bile and gallbladder tissue in patients with acute cholecystitis; Orda R et al.; The penetration of ceftriaxone and cefoperazone into bile and gallbladder tissue was prospectively studied in 21 adult patients undergoing early surgery for acute cholecystitis . Comparable tissue, bile, and serum concentrations of the drugs were demonstrable; however, significantly fewer preoperative doses of ceftriaxone were required for adequate perioperative treatment . In view of its higher serum half-life and superior antibacterial activity toward common biliary pathogens, ceftriaxone appears to be a useful drug for the perioperative management of acute cholecystitis.

Infect Immun, 1992 Nov, 60(11), 4754 - 61
High-affinity binding of the bactericidal/permeability-increasing protein and a recombinant amino-terminal fragment to the lipid A region of lipopolysaccharide; Gazzano-Santoro H et al.; Bactericidal/permeability-increasing protein (BPI) is a 55-kDa cationic protein (nBPI55) elaborated by polymorphonuclear neutrophils (PMN) . BPI has potent bactericidal activity against a wide variety of gram-negative organisms and neutralizes endotoxin activities . An N-terminal fragment of nBPI55 exhibits the bactericidal and antiendotoxin properties of the holoprotein . To further characterize the biological activities of the N-terminal fragment, a recombinant protein (rBPI23) corresponding to the first 199 amino acids of human BPI was produced and purified . rBPI23 had antibacterial activity equivalent to that of nBPI55 against Escherichia coli J5 . Furthermore, both rBPI23 and nBPI55 bound identically to a broad range of R- and S-form lipopolysaccharides (LPS) and to natural and synthetic lipid A . Binding of radiolabeled nBPI55 to LPS was inhibited in an identical fashion by either nBPI55 or rBPI23 . The binding of both proteins to immobilized E . coli J5 lipid A was inhibited in a comparable fashion by long- or short-chain LPS or lipid A . The binding of both rBPI23 and nBPI55 was specific, saturable, and of high affinity, with an apparent Kd of approximately 2 to 5 nM for all ligands tested . These results demonstrate that BPI recognizes the highly conserved lipid A region of bacterial LPS via residues contained within the amino-terminal portion of the BPI molecule.

J Ind Microbiol, 1992 Nov, 11(1), 13 - 8
Isolation, structure determination and biological activity of A-16686 factors A' 1, A' 2 and A' 3 glycolipodepsipeptide antibiotics; Gastaldo L et al.; When Actinoplanes strain ATCC 33076, the producer of A-16686 A1, A2 and A3 complex, is fermented in a suitable medium three additional factors, designated A' 1, A' 2 and A' 3 are produced . These were isolated and characterized, and were shown to differ from the parent components of the original complex by lacking one mannose unit . Bioconversion of A factors into A' factors was achieved by incubation with the mycelium of Actinoplanes ATCC 33076 . Factor A' 2 has better antibacterial activity than A2 against some bacteria.

J Hosp Infect, 1992 Nov, 22 Suppl A, 9 - 21
A meta-analysis of the use of amoxycillin-clavulanic acid in surgical prophylaxis; Wilson AP et al.; The efficacy of amoxycillin-clavulanic acid as antibiotic prophylaxis in surgery has been assessed in numerous clinical studies, chiefly in abdominal and gynaecological surgery . A meta-analysis of 21 trials covering 2685 patients given amoxycillin-clavulanic acid and 2220 patients given comparator regimens is presented . Monotherapy with amoxycillin-clavulanic acid was as effective as the comparators, including combination regimens utilizing gentamicin or metronidazole, in preventing wound infections (median wound infection rates were 6% and 10% respectively) . The antibacterial activity of amoxycillin-clavulanic acid covers the broad range of aerobic Gram-negative and anaerobic organisms that have a major role in postoperative infections . In addition, amoxycillin-clavulanic acid may have benefits in terms of convenience, tolerance and cost.

J Pharm Pharmacol, 1992 Nov, 44(11), 915 - 20
Effect of fenbufen on the entry of new quinolones, norfloxacin and ofloxacin, into the central nervous system in rats; Ichikawa N et al.; The entry of two new quinolone antibacterial agents, norfloxacin and ofloxacin, into the central nervous system (CNS) of rats, and the effect of fenbufen on this was investigated . At various times after the administration of a bolus intravenous dose of norfloxacin or ofloxacin (10 mg kg-1) with or without fenbufen (20 mg kg-1), serum and cerebrospinal fluid (CSF) samples and whole brain were collected from the rats and the concentration of norfloxacin or ofloxacin in each sample was determined . Serum concentrations of both quinolones declined biexponentially with time and were significantly elevated by coadministration with fenbufen at the terminal phase . The fractions of these quinolones bound to serum protein were not altered by coadministration with fenbufen . Coadministered fenbufen raised the brain concentrations of both quinolones but did not affect their brain to serum unbound concentration ratios . In contrast, CSF to serum unbound concentration ratios as well as CSF concentrations of norfloxacin and ofloxacin were elevated by coadministration with fenbufen . Apparent diffusional clearances between blood and CSF of norfloxacin and ofloxacin estimated by the physiological model analysis increased by 1.9 and 2.6 times, respectively, after coadministration with fenbufen . These findings suggest that coadministered fenbufen may facilitate the entry of norfloxacin and ofloxacin into the CNS.

J Antimicrob Chemother, 1992 Nov, 30(5), 673 - 83
Effect of fenbufen on the pharmacokinetics of sparfloxacin in rats; Naora K et al.; The effects of fenbufen on the serum concentrations and penetration into the brain and CSF of sparfloxacin (AT-4140), a new quinolone antibacterial agent, were investigated in rats . At designated times after a bolus iv dose of sparfloxacin 10 mg/kg with or without fenbufen 20 mg/kg, arterial blood, CSF and whole brain were simultaneously collected from each rat . Sparfloxacin concentrations were assayed by HPLC . Serum concentration of sparfloxacin declined bi-exponentially with time and was not changed by coadministered fenbufen . Binding sparfloxacin to serum protein slightly decreased after the coadministration . No elevation of sparfloxacin concentrations was observed in either brain or CSF after coadministration with fenbufen except for only a few time-points . The pharmacokinetic analysis based on the physiological model indicated that fenbufen did not affect the permeability across the blood-brain or blood-CSF barrier . These results suggest that fenbufen may be unlikely to affect the pharmacokinetics, involving the entry into the central nervous system, of sparfloxacin.

Arch Biochem Biophys, 1992 Nov 1, 298(2), 602 - 11
Stimulation of microsomal production of reactive oxygen intermediates by rifamycin SV: effect of ferric complexes and comparisons between NADPH and NADH; Kukielka E et al.; Rifamycins are antibacterial antibiotics which are especially useful for the treatment of tuberculosis . Reactive oxygen intermediates are produced in the presence of rifamycin SV and metals such as copper or manganese . Experiments were carried out to evaluate the interaction of rifamycin SV with rat liver microsomes to catalyze the production of reactive oxygen species . At a concentration of 1 mM, rifamycin SV increased microsomal production of superoxide with NADPH as cofactor 3-fold, and with NADH as reductant by more than 5-fold . Rifamycin SV increased rates of H2O2 production by the microsomes twofold with NADPH, and 4- to 8-fold with NADH . In the presence of various iron complexes, microsomes generated hydroxyl radical-like (.OH) species . Rifamycin SV had no effect on NADPH-dependent microsomal .OH production, irrespective of the iron chelate . A striking stimulation of .OH production was found with NADH as the reductant, ranging from 2- to 4-fold with catalyst such as ferric-EDTA and ferric-DTPA to more than 10-fold with ferric-ATP, -citrate, or -histidine . Catalase and competitive .OH scavengers lowered rates of .OH production (chemical scavenger oxidation) and prevented the stimulation by rifamycin . Superoxide dismutase had no effect on the NADH-dependent rifamycin stimulation of .OH production with ferric-EDTA or -DTPA, but was inhibitory with the other ferric complexes . In contrast to the stimulatory effects on production of O2-., H2O2, and .OH, rifamycin SV was a potent inhibitor of microsomal lipid peroxidation . These results show that rifamycin SV stimulates microsomal production of reactive oxygen intermediates, and in contrast to results with other redox cycling agents, is especially effective with NADH as the microsomal reductant . These interactions may contribute to the hepatotoxicity associated with use of rifamycin, and, since alcohol metabolism increases NADH availability, play a role in the elevated toxic actions of rifamycin plus alcohol.

Mycoses, 1992 Nov-Dec, 35(11-12), 301 - 3
Trichoderma viride infection in a liver transplant recipient; Jacobs F et al.; A liver transplant recipient developed infection of a perihepatic haematoma due to Trichoderma viride . Before the infection was diagnosed, the patient received intense immuno-suppressive and prolonged antibacterial and anti-fungal therapies . Although the death of the patient was not directly related to the fungal infection, abundant quantities of this pathogen were recovered in the haematoma at post-mortem examination, despite previous surgical removal and treatment with amphotericin B and fluconazole.

Antibiot Khimioter, 1992 Nov, 37(11), 35 - 7
{Experimental rationale for the feasibility of using sulacillin for the prevention of infectious complications of combined radiation and thermal injuries}; Budagov RS et al.; Concurrent radiation and thermal injury (IRTI) was simulated in Wistar rats . For prevention of the autoinfectious complications sulacillin, a combination of ampicillin and sulbactam, was used . The use of sulacillin was started on the onset of IRTI and continued for 7 days . The drug was administered intramuscularly twice a day . It was observed that the 8-day survival of the animals increased by more than 40 per cent and the statistical levels of bacteremia and bacterial endotoxemia significantly decreased . The experiments showed that sulacillin had no side immunodepressive effect and did not aggravate the affection of the blood system . The drug was recommended for further studies to provide evidence for rational schemes of antibacterial therapy in IRTI.

Klin Med (Mosk), 1992 Nov-Dec, 70(11-12), 53 - 5
{A new approach to the antibacterial therapy of chronic antral gastritis associated with Helicobacter pylori}; Masevich TsG et al.; The authors proposed an original method of treatment for antral gastritis associated with Helicobacter pylori and combined with duodenal ulcer . The principle of the method consists in a successive gastric lavage with alkaline and antibacterial (metronidazole) solutions twice a week for a fortnight . Three groups of patients were under observation (37 examinees with chronic antral gastritis associated with Helicobacter pylori and combined with duodenal ulcer) . Ten persons who were enlisted into the first group were treated with the lavage only, the second group persons (n = 12) were treated with lavages and histodyl in a dose of 400 mg per night, the third group (n = 15) were orally treated with metronidazole (0.25 g three times a day) for 15 days . A total elimination of Helicobacter pylori was observed in the half of the first group, 2/3 of the second and in 1/3 of the third group . Epithelialization of duodenal ulcers was observed in all those enlisted in the first and second group . Cicatrization of ulcers was observed in half of the patients from the third group.

Leuk Lymphoma, 1992 Nov, 8(4-5), 353 - 9
The use of fluconazole prophylaxis in patients with chemotherapy-induced neutropenia; Wingard JR; Systemic Candida infections are a major cause of infectious morbidity and mortality during chemotherapy-induced neutropenia . Because of the unreliability of conventional diagnostic tests to detect systemic infection early in its course, treatment of established disseminated Candida infection has been generally disappointing with mortality rates of 60-80% in leukemia and bone marrow transplant patients and 30-40% in solid tumor patients . The use of empiric amphotericin B in patients with fever not responding to empiric antibacterial agents has been shown to be successful in reducing morbidity and mortality from fungal infections . However, its toxicity has mitigated the success of this approach . Fluconazole given prophylactically at the institution of chemotherapy has been shown to be a safe and effective alternative . It, however, is not active against all fungal species, especially Aspergillus and some of the less virulent Candida species . Some centers have reported break-through infections by these less susceptible organisms . Whether or not these limitations in its spectrum of activity will limit its usefulness in the future remains unanswered at this time and could pose a cloud to an otherwise bright promise.

Minerva Chir, 1992 Oct 31, 47(20), 1623 - 5
{Evolution of the bacteria responsible for surgical infection . n 8-year study in our department}; Trabucchi E et al.; Since 1981 we monitored all the bacteria strains isolated from patients bearing a surgical infection and hospitalized in our department . We also tested the susceptibility of the isolated strains to different antibiotics . The observed results at three different intervals (1981, 1984, 1987-1988) reveal an increase in Gram+strains . Among the tested antibiotics Imipenem and Amikacin showed the highest antibacterial activity in recent years (1987-1988).

J Chromatogr, 1992 Oct 30, 624(1-2), 425 - 37
Methods for the determination of sulphonamides in meat; Guggisberg D et al.; Sulphonamides, due to their important antibacterial effects, are widely used in veterinary practice and animal husbandry . Residues arising from administration without observing withdrawal time sufficiently are normally the parent compounds and the N4-acetyl derivatives, the latter being hydrolyzed to the parent compounds only during extraction under acidic conditions . It is therefore quite conceivable that many authors concentrate on determining these metabolites . In the past decade, we have witnessed a considerable increase in new analytical techniques dealing with the determination of sulphonamides . Among these procedures, especially the so-called multimethods using high-performance liquid chromatography--though sometimes including toilsome clean-up steps--can be mentioned . However, current approaches also utilize gas chromatography, gas chromatography-mass spectrometry, liquid chromatography-mass spectrometry, supercritical fluid chromatography-mass spectrometry, thin-layer chromatography and immunological methods . For most of these techniques, a strong trend towards lowering the level of detectability (down to the sub-ppb range) and improving accuracy and reproducibility can be established.

Vet Rec, 1992 Oct 17, 131(16), 367 - 9
Significance of the vaginal bacterial flora in the bitch: a review; van Duijkeren E; The literature on the bacterial flora in the vagina of the bitch is reviewed . The bacterial flora in the vagina of healthy bitches is compared with the flora of infertile bitches and bitches with vaginitis, and the role of Brucella canis as a cause of infertility is evaluated . Several investigators have recommended that bitches with reproductive disorders be treated with antibacterial drugs, but there is very little knowledge of the effect of this therapy on the bacterial flora in the vagina.

Proc Natl Acad Sci U S A, 1992 Oct 15, 89(20), 9671 - 5
Quinolone binding to DNA is mediated by magnesium ions; Palu G et al.; The binding of plasmid DNA to norfloxacin, a quinolone antibacterial agent, was investigated by fluorescence, electrophoretic DNA unwinding, and affinity chromatography techniques . The amount of quinolone bound to DNA was modulated by the concentration of Mg2+ . No interaction was evident in the absence of Mg2+ or in the presence of an excess of Mg2+, whereas maximum binding was observed at a Mg2+ concentration of 1-2 mM . The experimental data can be fitted to the formation of three types of Mg adducts: a binary adduct with norfloxacin and Mg2+, a binary adduct with DNA and Mg2+, and a ternary adduct with quinolone, plasmid, and Mg2+ . We propose a model for the ternary complex, in which Mg acts as a bridge between the phosphate groups of the nucleic acid and the carbonyl and carboxyl moieties of norfloxacin . Additional stabilization may arise from stacking interactions between the condensed rings of the drug and DNA bases (especially guanine and adenine), which may account for the preference exhibited by quinolones for single-stranded and purine-rich regions of nucleic acids . Other possible biochemical pathways of drug action are suggested by the observation that norfloxacin binds Mg2+ under conditions that are close to physiological.

Dtsch Med Wochenschr, 1992 Oct 2, 117(40), 1513 - 7
{Lemierre's syndrome with splenic abscesses}; Kern W et al.; A week after onset of a pharyngo-tonsillitis a previously healthy 23-year-old man developed high fever (41.4 degrees C), leukocytosis (12,200/microliters) with marked shift to the left, thrombocytopenia (86,000/microliters) and increased transaminases (GOT 83 U/l, GPT 113 U/l) . Chest x-ray film suggested intrapulmonary abscesses with left-sided pleural effusion . The suspected diagnosis of "post-tonsillitis" septicaemia (Lemierre's syndrome) was confirmed by demonstrating anaerobic, fusiform, gram-negative bacteria (Fusobacterium nucleatum and necrophorum) in several blood cultures . Despite antibacterial treatment (amoxicillin/clavulanic acid, imipenem/cilastatin, clindamycin) he had recurrent pain referred to the kidney region and persisting fever . Repeated ultrasound and radiological examinations revealed new foci in the spleen, which were enlarging . Laparotomy with splenectomy performed on day 17 after the begin of treatment confirmed multiple splenic abscesses, but abscess pus and splenic tissue were sterile . After altogether 6 weeks of antibiotic treatment, finally with chloramphenicol, the patient was discharged in a good general state.

Mol Cell Probes, 1992 Oct, 6(5), 401 - 10
Detection of Mycobacterium leprae and the potential for monitoring antileprosy drug therapy directly from skin biopsies by PCR; Williams DL et al.; An improved protocol for PCR analysis of Mycobacterium leprae-infected tissues, based on enzymatic lysis, has been developed and used to demonstrate the feasibility of using PCR for detecting M . leprae in routine skin biopsies taken from leprosy patients throughout the clinical spectrum . Of 92 multibacillary patients tested, 99% were PCR-positive using gel electrophoresis or DNA hybridization to detect the amplified product . Similar analysis of paucibacillary patients, in which only one of 27 biopsies had demonstrable AFB microscopically, gave a positivity rate of 74% . No PCR signals were demonstrated from skin biopsies from seven patients with non-leprosy dermatoses and one AIDS patient with a disseminated atypical mycobacteriosis . Evaluation of leprosy patients with antileprosy drug therapy prior to biopsy demonstrated that PCR signals were either greatly diminished or absent after 2 months of continuous antibiotic therapy . PCR was also able to detect the presence of M . leprae in tissues of patients receiving antibacterial therapy when patients were suspected of harbouring drug-resistant M . leprae.

J Antibiot (Tokyo), 1992 Oct, 45(10), 1677 - 80
Total syntheses of bellenamine and its isomers; Ikeda Y et al.; The total synthesis of bellenamine was achieved by a modified CURTIUS procedure starting with D-beta-lysine . Bis(N-benzyloxycarbonyl)-D-beta-lysylglycine was converted to tris(N-benzyloxycarbonyl)bellenamine which was catalytically hydrogenated to yield bellenamine . D-beta-Lysine was synthesized from D-ornithine by the ARNDT-EISTERT homologation sequence . Three isomers, L-beta-lysyl, D- and L-lysyl congeners synthesized by a similar method, showed no antibacterial activities.

Acta Ophthalmol (Copenh), 1992 Oct, 70(5), 698 - 701
Acanthamoeba keratitis; report of the first Norwegian cases; Aasly K et al.; Two patients with therapy resistant keratitis are described . There were no predisposing diseases . Both patients had been using rigid contact lenses for more than 10 years and both cleaned their lenses in cold tap water . The patients presented with keratitis of several weeks duration resistant to antibacterial and antiviral treatment and not responding to high doses of corticosteroids . Ultimately, after the possibility of a protozoan aetiology had been considered, culture of corneal scrapings from both patients yielded growth of Acanthamoeba trophozoites . Acanthamoeba keratitis is very rare in northern European countries and has never before been diagnosed in Norway . The present cases show that Acanthamoeba should be added to the list of possible pathogenic agents even in northern low temperature areas.

Atherosclerosis, 1992 Oct, 96(2-3), 147 - 58
Effect of a novel series of macrocyclic hypolipidemic agents on plasma lipid and lipoprotein levels of four non-primate species; Gibson JC et al.; The ansamycins are structurally novel hypolipidemic agents derived from rifampicin, but lacking antibacterial activity . Oral or intravenous administration resulted in rapid lowering of plasma cholesterol in rats, hamsters, guinea pigs and dogs . In the chow-fed rat, three related compounds (CGP 43371, CGS 23810 and CGS 24565) exhibited ED50 values of 13.7, 3.1 and 0.18 mg/kg, respectively . A feature common to the lipid lowering documented in these four species was the concomitant reduction of low density lipoprotein (LDL) and high density lipoprotein (HDL) cholesterol . In the chow-fed rat, however, apolipoprotein AI (apo AI) levels were much less affected than were those of HDL cholesterol . CGP 43371 at 3 and 10 mg/kg, lowered HDL cholesterol by 20% and 39%, respectively, whereas plasma apo AI was reduced by only 1% and 12% . Similarly, in lipoprotein fractions separated by ultracentrifugation, apo AI was unchanged in the d = 1.019-1.21 g/ml fraction after treatment with 3 or 10 mg/kg of CGP 43371, but HDL cholesterol was reduced 12% and 26% in this fraction at the two dose levels . Plasma and lipoprotein apo B levels, on the other hand, were reduced to a level equivalent to that of the reduction in cholesterol . The ansamycins thus represent a new structural series which may possess a novel mechanism of action as well, involving differential effects on HDL cholesterol and protein.

Indian J Med Res, 1992 Oct, 96, 292 - 6
Effect of three antibacterial drugs in lowering blood & stool ammonia production in hepatic encephalopathy; Alexander T et al.; Neomycin (700 mg/8 h), ampicillin (500/6 h) and metronidazole (400 mg/8 h), were compared for their effect, on oral administration for 4 days, in reducing blood ammonia in 27 patients with stable chronic liver disease . It was found that there was 38.2, 38.5 and 8.7 m mol/litre mean reduction in blood ammonia in the neomycin, ampicillin and metronidazole treated groups respectively . The difference in blood ammonia was statistically significant for both neomycin (P = 0.01) and ampicillin (P = 0.03) but there was no significant change after metronidazole treatment (P = 0.6) . The total stool enzyme activity at optimum pH was maximally reduced by ampicillin and minimally with metronidazole . The reduction was noted to be 3.51 m mol/1 (P = 0.01), 3.87 m mol/1 (P = 0.08) and 2.8 m mol/1 (P = 0.02) of NH3/g dry weight of stool for neomycin, ampicillin and metronidazole respectively . The main bacterial gut enzymes responsible for ammonia production, urease and protease, were found to be very sensitive to stool pH . At pH 6 their activity was around 20 per cent of what was found in optimum pH of 7.4 and at pH 5 it is only about 8 per cent of optimum activity . None of the three antibacterial agents changed the stool pH significantly . It can be concluded that oral neomycin and ampicillin are superior to oral metronidazole in lowering blood ammonia.

Vet Hum Toxicol, 1992 Oct, 34(5), 393 - 7
An analytical study of antibacterial residues in meat: the simultaneous determination of 23 antibiotics and 13 drugs using gas chromatography; Mineo H et al.; Simultaneous determination of 7 penicillins, 3 tetracyclines, 5 aminoglycoside antibiotics, 5 macrolide antibiotics, 2 polyether antibiotics, chloramphenicol and 13 drugs was evaluated . The 36 agents in meat were extracted with 10% trichloroacetic acid . The extracted solutions were adsorbed on an Amberlite XAD-2 resin column and an activated carbon resin column and then eluted with methanol and 0.01N HCl-methanol, respectively . The eluted solutions were concentrated to dryness and trimethylsilylated with pyridine, N, 0-bis (trimethylsilyl) acetamide, N-trimethylsilylimidazole and trimethylchlorosilane . They were then measured by gas chromatography with a flame-ionization detector . The recovery for almost all of the 36 compounds from the original meat specimens was more than 82% . The limits of detection for most of the 36 agents using this method were equivalent to the original individual methods of analysis.

Can J Ophthalmol, 1992 Oct, 27(6), 313 - 5
Drug-induced fatal aplastic anemia following cataract surgery; McWhae JA et al.; Aplastic anemia attributed to medications used in ophthalmology is rare . We report a fatal case that developed in a 73-year-old woman 7 weeks after cataract extraction performed under local anesthesia . Postoperative medications included a chloramphenicol-containing ointment, flurbiprofen sodium drops, prednisone acetate drops and orally given acetazolamide . It was felt that the aplastic anemia was related to therapy with chloramphenicol or acetazolamide or both . We recommend that the course of prophylactic antibacterial therapy after intraocular surgery be kept short, regardless of the preparation used . We urge caution in the choice and use of drugs known to be associated with aplastic anemia and recommend close monitoring of the hemogram.

Thromb Res, 1992 Oct 1, 68(1), 1 - 32
Molecular mechanism of hemolymph clotting system in Limulus; Iwanaga S et al.; Limulus (horseshoe crab) hemolymph is known to be very sensitive to bacterial endotoxin (LPS), which causes a rapid coagulation response . Hemolymph contains a single type of hemocyte that undergoes aggregation, adhesion, and degranulation in response to LPS . The granule contents are released into the hemolymph, where they form an insoluble gel . We have characterized four components involved in this coagulation response that comprise a cascade of three serine protease zymogens (factor C, factor B, and proclotting enzyme) and one clottable protein (coagulogen) . Of these components, factor C sensitive to LPS is a protein composed of five complement-related domains ("Sushi" or SCR), an EGF-like domain, and a C-type lectinlike domain as well as a putative amino-terminal LPS-binding domain . This domain structure is very similar to that of selectin family of cell adhesion molecules, suggesting that it might also function as a cell adhesion molecule after the release into the hemolymph . Factor B and the proclotting enzyme share a common Cys-rich motif ("cliplike" domain) in the amino-terminal portions . This domain is also found in a putative serine protease zymogen ("easter") in Drosophila, which is essential for normal embryonic development . All four of the components of the cascade and an antibacterial protein (anti-LPS factor) are localized to a specific type of the hemocyte granule . Another antibacterial peptide (tachyplesins I and II) is localized in a distinct granule population . The contents of both granule populations are released into the hemolymph in response to LPS, where they cooperate in immobilization and killing of Gram-negative bacteria.

Immunol Today, 1992 Oct, 13(10), 411 - 5
Insect defensins: inducible antibacterial peptides; Hoffmann JA et al.; In response to bacterial challenge or trauma, insects produce a battery of bactericidal or bacteriostatic molecules with a broad spectrum of activity against Gram-positive and/or Gram-negative bacteria; most are small-sized cationic peptides . This review focuses on insect defensins, a large group of inducible antibacterial peptides that are present both in ancient and recent insect orders . This immune response of insects shares many of the characteristics of the mammalian acute phase response.

Eur J Biochem, 1992 Oct 1, 209(1), 163 - 9
The structure of the mammalian antibacterial peptide cecropin P1 in solution, determined by proton-NMR; Sipos D et al.; Cecropins are peptides with antibacterial activity originally found in insects . Recently a cecropin-type peptide was isolated from pig intestine . This peptide, porcine cecropin P1, which has 31 amino acid residues and is not amidated in the C-terminus, has been synthesized, purified, and investigated by CD and two-dimensional 1H-NMR at pH 5.0 in aqueous solution with 30% (by vol.) 1,1,1,3,3,3-hexafluoro-2-propanol . All proton resonances have been assigned except for the N-terminal serine . Using constraints derived from NOE connectivities and 3JNH alpha-coupling constants, three-dimensional structures have been calculated by means of a distance-geometry program . Some of these structures have been refined by energy minimization and restrained molecular dynamics . The structures reveal an alpha-helix of approximately seven turns along nearly the full length of the peptide . The central part of the helix is very well defined by the NMR constraints . Also the chemical shifts of the alpha protons and the results of CD measurements are in accord with this structure, which is different from the helix-hinge-helix structure earlier found in cecropin A and related peptides . In the alpha-helix of cecropin P1 there is a long amphipathic section, of 4-5 turns, and a short hydrophobic section of one to two turns, with an intervening Glu-Gly sequence, which is a potential bend-forming section . The helix can easily span a lipid membrane.

Eur J Biochem, 1992 Oct 1, 209(1), 1 - 6
Molecular cloning of the antibacterial protein of the giant African snail, Achatina fulica Férussac; Obara K et al.; An expression cDNA library was constructed with poly(A)-rich RNA extracted from the collar of the giant African snail, Achatina fulica Ferussac . A 1.9-kbp cDNA clone encoding a precursor of antibacterial glycoprotein of the snail, achacin, was isolated from the cDNA expression library . The cDNA sequence contains an open reading frame with 1593-nucleotide residues . The deduced amino acid sequence of this achacin precursor starts with a 29-residue leader peptide followed by a 502-residue mature peptide (56 kDa) with four possible N-glycosylation sites, Asn-Xaa-Ser or Asn-Xaa-Thr . The Northern-blot analysis proved that the achacin precursor was specifically expressed in the tissue of snail collar and processed to mature achacin . cDNA inserts encoding achacin precursor were subcloned into expression plasmids . Three kinds of expressed polypeptides were cross-reacted with rabbit antiserum raised against achacin . The largest polypeptide (M(r) 63,000) should be the achacin precursor.

Biosci Biotechnol Biochem, 1992 Oct, 56(10), 1570 - 6
Isolation and characterization of macrocarpals B--G antibacterial compounds from Eucalyptus macrocarpa; Yamakoshi Y et al.; Six novel phloroglucinol dialdehyde diterpene derivatives (macrocarpals B--G), which have antibacterial activity, were isolated from leaves of Eucalyptus macrocarpa . These compounds have closely related structures, the molecular formula for B--F being C28H40O6, and that of G being C28H38O5 . The structures of macrocarpals B, D, and G were analyzed by means of NMR analyses.

Aktuelle Traumatol, 1992 Oct, 22(5), 214 - 8
{Clinical experience with collagenous wound dressing in severe traumatic soft tissue injuries}; Goudarzi YM et al.; We treated 34 patients during 1987-1990 with a collagen wound dressing . Eleven patients had traumatic soft tissue defects, 10 patients had 3 degrees-grade open fractures, 7 patients had infected soft tissue wounds and 6 patients had deep 2 degrees and 3 degrees-degree burns . Our clinical experience confirmed the excellent clinical experimental results of collagen wound dressings . In all cases after 4 until 6 days of treatment good granulation and vascularisation of the wound bed was obtained, so that a skin transplant could be performed, which in all cases healed primarily . Moreover, the wound dressing had a good antibacterial effect and integrated actively in the wound healing process.

Kansenshogaku Zasshi, 1992 Oct, 66(10), 1462 - 72
{Dose finding study of sparfloxacin in single-dose therapy for female acute uncomplicated cystitis}; Hirose T et al.; Sparfloxacin (SPFX) is a new quinolone compound with a long half-life of 16 hours and a potent antibacterial activity (MIC90: < or = 0.025 micrograms/ml against Escherichia coli), suggesting that the agent can be effectively used in single-dose therapy for acute uncomplicated cystitis in female patients . To find the optimum dose, the present dose-finding study was conducted . A dose of either 100 mg or 200 mg of SPFX was selected by the double-blind method, and was administered only once (single dose therapy) . The clinical efficacy was judged on day 3, 7 and 14 after administration . On day 3, of the 49 pts . in the 100 mg-group, the efficacy rate was 95.9% (excellent rate: 79.6%), and of the 42 pts . in the 200 mg-group, it was 100% (excellent rate: 88.1%) . On day 7, of 38 pts . in the 100 mg-group, it was 94.7% (excellent rate: 78.9%), and of 28 pts . in the 200 mg-group, it was 100% (excellent rate: 92.9%) . On day 14, of 27 pts . in the 100 mg-group, it was 92.6% (excellent rate: 66.7%), and of 26 in the 200 mg-group, it was 96.2% (excellent rate: 84.6%) . Recurrence was observed in 4.8% (1/21) in the 200 mg-group . Therefore, there was no significant difference in the efficacy rate between the two groups, but the rate of excellent responses was higher in the 200 mg-group . Otherwise, the efficacy was estimated to be insufficient in 3 pts . and recurrent in 1 pt . they were examined the findings of detailed urological intractableness . Among 2 pts . in whom the external genitalia and urethra were closely examined, a urethral caruncle was noted in 1 pt . The results of our study indicate that 200 mg of SPFX is recommended as a single dose therapy for acute uncomplicated cystitis in females.

Nippon Ganka Gakkai Zasshi, 1992 Oct, 96(10), 1229 - 33
{The dynamics of melanin-affinitive and non-affinitive antibacterial agents in the iris-ciliary body of rabbit eyes--comparative studies in pigmented and albino rabbits}; Fukuda M et al.; The differences between the drug penetration levels in the iris-ciliary bodies of sparfloxacin (SPFX) and cefmenoxime (CMX), which respectively have high and low affinity to melanin, were examined using pigmented and albino rabbit eyes . Each drug was mixed with a homogenate of the iris-ciliary bodies of pigmented and albino rabbit eye, respectively . All CMX was distributed in a water soluble protein of the above homogenate of both pigmented and albino eyes, while all SPFX was detected from the water soluble protein of the tissue homogenate of the albino eye . However, in homogenate of the pigmented eyes, 60% of the drug was detected from water soluble protein and 20% of that was detected from water non-soluble protein . In the in vivo study, each drug was topically administered to pigmented and albino rabbit eyes . The SPFX concentration in the iris-ciliary body was significantly higher in the pigmented than in the albino eyes . The results indicated that the intraocular dynamics of the drug which has a high affinity to melanin showed significant differences between pigmented and albino rabbit eyes . This should be considered in studies of ocular pharmacology as an important factor which influences intraocular drug dynamics.

Antibiot Khimioter, 1992 Oct, 37(10), 44 - 6
{Immunochemotherapy of infants in the first year of life with intestinal infections due to opportunistic gram-negative aerobic bacteria}; Litiaeva LA; The clinical and microbiological observations of 50 babies of the 1st year of age with intestinal infections due to opportunistic organisms were made . The babies were treated with antibacterial drugs and an immunoglobulin preparation . It was shown that the combined use of antibacterial and immunological preparations in the treatment of the babies with the intestinal infections caused by opportunistic organisms provided their earlier clinical recovery and lowered the unfavourable effect of the antibacterial drugs on the intestinal microflora.

Antibiot Khimioter, 1992 Oct, 37(10), 29 - 31
{Detection of persistent resistance to antibacterial drugs in various strains of Francisella tularensis}; Pavlovich NV et al.; Under natural conditions, the Francisella tularensis strains AE-261 and P-13864 capable of forming the persist type of resistance to antibacterial drugs and being the cause of the infection in laboratory animals not responding to monotherapy with antibiotics were detectable . The antibioticograms of strains AE-261 and P-13864 under the in vitro conditions did not differ from those of the other studied strains responding to the antibiotic therapy . The observed phenomenon could be associated with individual peculiarities of the strains and their phenotypic variation in the host . Combinations of aminoglycoside antibiotics (streptomycin, gentamicin and amikacin) with rifampicin were shown to be highly active in the treatment of general forms of the infection due to such strains . The combined therapy of tularemia was also considered promising because of its high efficacy when the treatment was started at late periods as well as because unlike the monotherapy with the aminoglycoside antibiotics it provided complete elimination of the pathogen from the host.

Biochim Biophys Acta, 1992 Sep 24, 1132(2), 203 - 6
Isolation and nucleotide sequence of cecropin B cDNA clones from the silkworm, Bombyx mori; Taniai K et al.; Two cDNA clones encoding cecropin B, an antibacterial protein, were isolated from a fat body cDNA library of the silkworm, Bombyx mori . Amino acid sequences of these clones, deduced from nucleotide sequences, were identical, including signal peptide regions . However, the nucleotide sequences were different at 30 positions . Deduced amino acid sequences of Bombyx mori cecropin B showed higher homology with cecropins from Lepidoptera than with those from Diptera.

Yakugaku Zasshi, 1992 Sep, 112(9), 622 - 37
{Orally active cephalosporins . I . Synthesis and structure-activity relationships of 7 beta-{2-(R)-amino-2-phenylacetamido}-3-(1H- 1,2,3-triazol-4-yl)alkylthiomethyl-3-cephem-4-carboxylic acid and related compounds}; Kume M et al.; The synthesis, antibacterial activity and oral absorbability of 7 beta-{2-(R)-amino-2-phenylacetamido}-3-(1H-1H-1,2,3-triazol- 4-yl)methylthiomethyl-3-cephem-4-carboxylic acid (1a) and related compounds (1b-p and 2) are described . The replacement of 1,2,3-triazole at the C-3 position of 1a with other heteroaromatics such as 1,2,4-triazole, imidazole and so on decreased its oral absorbability in mice (1b-j) . The oral absorbability was also influenced by the spacer length between C-3 of cephem nucleus and C-4 of 1,2,3-triazole . The quantitative relationship between the bioavailability and the spacer length of cephalosporins (1a and 1k-p) is discussed . These results suggest that 1,2,3-triazole in the side chain at the C-3 position of cephems plays an important role in good oral absorption through its interaction with the transport system of small intestine.

Br J Gen Pract, 1992 Sep, 42(362), 362 - 5
Drug consumption during the first 18 months of life of infants from smoking and non-smoking families; Hakansson A et al.; In a geographically well defined population in southern Sweden, a study was made of the overall consumption of drugs by infants during their first 18 months of life . The study population comprised 240 infants, of whom 90 were from families where tobacco was smoked by one or both parents and 150 were from non-smoking families . The investigation was carried out retrospectively by interviewing the mothers at the routine 18-month check up at the child health clinic, combined with study of the medical records at the district health centre, and at the paediatric and ear, nose and throat departments of the nearby hospital . In addition, the reliability of the interview method compared with review of medical records was investigated . Particular attention was paid to the consumption of antibiotics and the relationship between 'passive smoking' and consumption of antibiotics necessitated by respiratory tract infections . There was widespread use of both prescribed and non-prescription remedies . At the age of 18 months, about two thirds of all infants in the area had been prescribed an antibiotic (or other antibacterial agent) on at least one occasion . Infants from smoking families had been prescribed significantly more antibiotics than had infants from non-smoking families . The same pattern was also apparent for nose drops and dimethicone/dicyclomine hydrochloride . The incidence of respiratory tract infections requiring antibiotic treatment was higher in infants from smoking families than from non-smoking families in all the three-month age groups up to 15 months . The responses to the retrospective interview accorded closely with the details recorded in the medical records.(ABSTRACT TRUNCATED AT 250 WORDS)

Zentralbl Veterinarmed B, 1992 Sep, 39(7), 537 - 45
In vitro antibacterial activity of the lactoperoxidase system towards enterotoxigenic strains of Escherichia coli; Grieve PA et al.; The lactoperoxidase-thiocyanate-hydrogen peroxide (LP) system inhibited the growth of enterotoxigenic Escherichia coli strains responsible for scouring in neonatal and post-weaning piglets . An enzymatic system for hydrogen peroxide generation (glucose oxidase, GO; 0.1 U/ml) and a chemical source (sodium carbonate peroxyhydrate, SCP; 90 mg/l) were used in the LP system to test 19 strains in a 6-h growth assay at 37 degrees C . Only three strains were highly sensitive to the LP/GO system, while all exhibited significant growth inhibition with the LP/SCP system . Hydrogen peroxide alone had less effect than the complete system . The bactericidal activity of the LP/GO system towards a previously resistant strain was greatly increased by increasing the level of glucose oxidase in the system by three- or five-fold.

Comp Biochem Physiol B, 1992 Sep, 103(1), 293 - 6
Selected biological activities of saraines; Caprioli V et al.; 1 . The Mediterranean sponge Reniera sarai, Pulitzeri-Finali, 1969 (Demospongiae: Haploscleridae: Renieridae) possesses in large amounts a series of unprecedented polycyclic alkaloids, saraines 1-3 and saraines A-C . 2 . The structural peculiarities of saraines, their chemical-physical characteristics, along with their relevant abundance in the sponge, prompted a study aimed at investigating their biological properties . 3 . Saraines were assayed for their cytotoxic, antibacterial, insecticidal and potential antitumoral activities . These results, along with the growth inhibition of fertilized sea urchin eggs, are reported.

Chem Pharm Bull (Tokyo), 1992 Sep, 40(9), 2410 - 8
Synthesis and antibacterial activity of 1-substituted-methyl carbapenems; Sendo Y et al.; The synthesis of the 1 alpha- and the 1 beta-substituted (fluoro, cyano, hydroxy and acetoxy)-methyl carbapenems having a 2-(1,3,4-thiadiazol-2-yl)thiomethyl side chain are described, and their in vitro antibacterial activities are compared with the corresponding 1 beta-methyl carbapenems together with imipenem . The synthesis and antibacterial activity of the 1 beta-substituted (fluoro and cyano)-methyl carbapenems having 2-(1-alkyl-4-pyridinio)thiomethyl side chains are also described.

Chem Pharm Bull (Tokyo), 1992 Sep, 40(9), 2331 - 7
Studies on the chemical modification of monensin . IV . Synthesis, sodium ion permeability, and biological activity of 7-O-acyl- and 7-O-alkylmonensins; Nakamura A et al.; 7-O-Acyl-(4a-e) and 7-O-alkylmonensins (5a-d) were prepared from monensin (1) . Their lipophilicity, sodium ion permeability in human erythrocytes, antibacterial activity and effect on rat tail artery were examined . There was a correlation between lipophilicity and sodium ion permeability as well as between lipophilicity and antibacterial activity . We also found that the compound having larger sodium ion permeability, showed stronger contraction of rat tail artery . 7-O-Benzylmonensin (5c) exhibited higher lipophilicity and larger sodium ion permeability than monensin (1) among the tested monensin derivatives . In addition, antibacterial activity and contractile effect on rat tail artery of 5c were comparable to those of 1.

Arzneimittelforschung, 1992 Sep, 42(9), 1125 - 9
Hypolipidaemic activity of a novel acyclic ansamycin derivative . Synthesis and pharmacokinetic and pharmacodynamic studies in rodents; Menear KA et al.; Certain classes of the antibacterial agent rifamycin SV have recently been shown to possess marked hypolipidaemic activity . An acyclic oxazolylrifamycin has been prepared and its hypolipidaemic properties evaluated; it was found to be significantly more potent when administered orally to Wistar and Sprague-Dawley rats than other previously described rifamycin hypolipidaemics . The plasma decay rate of a bolus of intravenously administered 125I-LDL (low density lipoprotein) was significantly greater in treated rats than in rats receiving vehicle alone, compatible with a drug-induced increase in LDL catabolism . A bolus of radiolabelled drug was rapidly removed from the circulation by the liver, the presumed target organ . Compound 3 constitutes the first example of a new class of acyclic hypolipidaemic ansamycins.

Analyst, 1992 Sep, 117(9), 1425 - 7
Simultaneous determination of some antibacterial drugs in isosensitest broth using high-performance liquid chromatography with solid-phase extraction; Taylor RB et al.; A method is described for the simultaneous determination of combinations of some antibacterial drugs in a matrix of isosensitest broth . A double solid-phase extraction procedure is described in which trimethoprim and dibromopropamidine isethionate together with 4-chlorophenylbiguanide as internal standard are freed from endogenous components by a cation-exchange extraction cartridge and subsequently removed and individually separated by reversed-phase ion-pair chromatography . Sulfadiazine, sulfamerazine and p-aminobenzoic acid, unretained by ion exchange, are similarly isolated for chromatography by adsorption on a CH-bonded phase cartridge and individually assayed using the same chromatographic system . The rationale of the pre-treatment and chromatography is described and the quantitative aspects of the analyses of selected combinations of these drugs are reported.

Z Gesamte Inn Med, 1992 Sep, 47(9), 398 - 403
{Antibiotic therapy of bacterial respiratory tract infections}; Schauer J; Infections of the airways are among the most frequent of inflammatory diseases appropriate for antibacterial therapy . One must differentiate between infections of the upper and lower airways, respectively infections obtained externally, and nosocomial infections . Since a relatively uniform spectrum of microbes can usually be expected, well-planned antibacterial therapy is possible . For nosocomial infections, on-target antibacterial therapy is required . For the various diseases of the airways, diagnostic and therapeutic strategies are outlined.

Z Gesamte Inn Med, 1992 Sep, 47(9), 386 - 90
{Treatment with antibacterial chemotherapy}; Schauer J et al.; The importance of a true indication of antimicrobiological chemotherapy is discussed on beginning of the paper . A correct choice of antibiotics and proper strategy of therapy will be demonstrated . Additionally essential antibiotics are presented.

Obstet Gynecol Clin North Am, 1992 Sep, 19(3), 563 - 85
Antiviral agents; Watts DH; Antiviral agents are less numerous and often more toxic than antibacterial agents . Acyclovir is commonly used for suppression and treatment of recurrent genital herpes simplex virus and may be indicated for pregnant women with disseminated herpes . Zidovudine is indicated for pregnant women with human immunodeficiency virus infection who have low CD4 lymphocyte counts . Ganciclovir, vidarabine, ribavirin, amantadine, didanosine, and foscarnet are rarely indicated in gynecology and are not recommended for use in pregnancy.

J Nat Prod, 1992 Sep, 55(9), 1165 - 9
A new acylated N-glycosyl lactam from Aristolochia contorta; Lee HS et al.; A new acylated glycoside isolated from the roots of Aristolochia contorta (Aristolochiaceae), has been characterized as aristolactam N-(6'-trans-p-coumaroyl)-beta-D-glucopyranoside {2} . Aristolactam-N-beta-D-glucopyanoside {1} was also isolated from the same source . Compound 2 showed relatively significant antibacterial activity against Gram-positive bacteria, based on disc diffusion and dilution methods.

Drug Saf, 1992 Sep-Oct, 7(5), 323 - 63
Adverse drug reactions to systemic antifungals . Prevention and management; Perfect JR et al.; Systemic administration of antifungal agents for invasive mycoses has dramatically increased over the past 10 years in many fields of medicine . The increase has been due both to an increasing immune compromised population and to potent antibacterial agents which allow these fungi to invade tissue . It is apparent that our understanding of the use of both the old and new antifungal agents has significantly increased in the last few years . In this review, we attempt to document our extensive knowledge of the adverse effects of the polyenes, flucytosine, griseofulvin and azoles when given systemically for treatment . Interwoven in this documentation of the adverse reactions to these agents is the attempt to help clinicians potentially avoid some of these adverse effects and if they do occur, to be able to identify and successfully manage them.

Pigment Cell Res, 1992 Sep, 5(3), 107 - 12
B700 antigen as a component of an antimelanoma vaccine: formalinized extracellular antigens; Shrayer D et al.; Formalin fixation has enjoyed widespread use in the preparation of antibacterial and other vaccines, but rather less use in antitumor vaccines . Previous studies from our laboratories have demonstrated the efficacy of antimelanoma vaccines in mice, produced from formalinized antigens shed by cultured melanoma cells . In this study, we provide evidence that the immunodominant component of that vaccine is the well-characterized B700 melanoma antigen.

Microbiol Rev, 1992 Sep, 56(3), 395 - 411
Agents that increase the permeability of the outer membrane; Vaara M; The outer membrane of gram-negative bacteria provides the cell with an effective permeability barrier against external noxious agents, including antibiotics, but is itself a target for antibacterial agents such as polycations and chelators . Both groups of agents weaken the molecular interactions of the lipopolysaccharide constituent of the outer membrane . Various polycations are able, at least under certain conditions, to bind to the anionic sites of lipopolysaccharide . Many of these disorganize and cross the outer membrane and render it permeable to drugs which permeate the intact membrane very poorly . These polycations include polymyxins and their derivatives, protamine, polymers of basic amino acids, compound 48/80, insect cecropins, reptilian magainins, various cationic leukocyte peptides (defensins, bactenecins, bactericidal/permeability-increasing protein, and others), aminoglycosides, and many more . However, the cationic character is not the sole determinant required for the permeabilizing activity, and therefore some of the agents are much more effective permeabilizers than others . They are useful tools in studies in which the poor permeability of the outer membrane poses problems . Some of them undoubtedly have a role as natural antibiotic substances, and they or their derivatives might have some potential as pharmaceutical agents in antibacterial therapy as well . Also, chelators (such as EDTA, nitrilotriacetic acid, and sodium hexametaphosphate), which disintegrate the outer membrane by removing Mg2+ and Ca2+, are effective and valuable permeabilizers.

J Gastroenterol Hepatol, 1992 Sep-Oct, 7(5), 533 - 7
Treatment of peptic ulcer disease with furazolidone; Zheng ZT et al.; Furazolidone (FZ) has been used in China as a treatment of peptic ulcer disease for about 20 years . Clinical and experimental studies suggest that it has good short-term and long-term effects on both human and animal ulcers . The ulcer healing rate is related to the dosage and course of treatment . The healing rate of a high dose, 2 week course is about 70-75% and the relapse rate after 3 years is 9.5% . The adverse reactions to FZ are not severe, and are well tolerated in most patients . However the mutagenic studies of several biological systems indicate that it has a mutagenic effect, but the mutagenic and carcinogenic effects on humans and animals remain questionable, because FZ has been biotransformed into other metabolites . The mechanisms of FZ in the treatment of peptic ulcer disease are not fully understood, perhaps partly due to the monoamine oxidase (MAO) inhibitory reaction and partly to the antibacterial activity to Helicobacter pylori (HP) . The long-term effects of FZ are still not clear.

Ann Hematol, 1992 Sep, 65(3), 138 - 42
Histoplasmosis in hairy cell leukemia: case report and review of the literature; Weeks E et al.; Progressive disseminated histoplasmosis (PDH) has been described in only six patients with hairy cell leukemia (HCL) . Herein we describe an additional patient with HCL and disseminated histoplasmosis . Additionally, we note that three of seven cases of disseminated histoplasmosis and HCL have occurred in East Texas . PDH is to be suspected in febrile HCL patients in an endemic area who fail to respond to antibacterial therapy . We emphasize that serologic studies are useful in the diagnosis of PDH in HCL patients, and these patients respond well to therapy.

Blood, 1992 Sep 1, 80(5), 1163 - 71
Antibody responses to bacteriophage phi X174 in patients with adenosine deaminase deficiency; Ochs HD et al.; Adenosine deaminase (ADA) deficiency and its biochemical consequences cause severe combined immunodeficiency (SCID) . Treatment strategies, designed to correct the biochemical abnormalities, include transplantation of matched bone marrow or haploidentical bone marrow stem cells, repeated partial exchange transfusions with frozen irradiated human red blood cells (RBC), or weekly injection of polyethylene glycol-modified bovine ADA (PEG-ADA) . To evaluate the effect of these therapeutic options, we studied in vitro T-cell function and in vivo antibody responses to the T-cell-dependent neoantigen, bacteriophage phi X174, in 10 children with ADA-deficient SCID . In untreated patients, T-cell function was severely depressed, and only minute amounts of antibacteriophage antibody were produced . Transplantation of bone marrow from a matched sibling (one patient) or a phenotypically matched parent (one patient) resulted in a stable graft, normal T-cell function, and substantial but subnormal antibody titers to bacteriophage, with reduced memory and impaired switch from IgM to IgG . Patients receiving T-cell-depleted haploidentical bone marrow stem cells had markedly depressed antibody responses for as long as 3 years posttransplantation, despite rapidly improving T-cell function that became normal in two of four patients . Two methods of enzyme replacement were explored . During treatment with human RBC transfusions, antibody responses to bacteriophage were as severely depressed as in untreated ADA-deficient patients . Treatment with weekly injections of PEG-ADA resulted in normalization of T-cell numbers in all four patients, normal or near-normal T-cell function in two, and mildly but variably improved T-cell function in the other two patients . Quantitatively and qualitatively normal antibody responses to bacteriophage were observed in three of four patients . Assessment of antibody responses to immunization with bacteriophage phi X174 is a useful method to monitor humoral immune function in treated ADA-deficient patients and can be used to estimate when intravenous immunoglobulin (IVIG) prophylaxis may be safely discontinued.

Vestn Khir Im I I Grek, 1992 Sep-Oct, 149(9-10), 206 - 15
{Wound infection}; Eriukhin IA et al.; A present-day view on the problem of wound infection is analyzed with special reference to recent data . Active surgical approach in combination with many-component antibacterial and correcting treatment still remains important in prevention and treatment of wound infection.

Pharmazie, 1992 Sep, 47(9), 707 - 9
On the protonophoric activity of oxazolomycin; Grigorjev PA et al.; By the use of an artificial lipid membrane model we have shown that the antibiotic oxazolomycin (Streptomyces albus) is an effective protonophore at pH < 7.0 but conveys both protons and monovalent cations such as potassium at pH > 7.5 as a passive carrier . The ionophoric properties are suggested to be correlated with its antibacterial, antiviral, and cytotoxic activities.

Free Radic Biol Med, 1992 Sep, 13(3), 187 - 95
Free radical generation and coupled thiol oxidation by lactoperoxidase/SCN-/H2O2; Lovaas E; The lactoperoxidase-catalyzed oxidation of glutathione (GSH) and thiocyanate (SCN-) was studied . Oxidation of SCN- was recorded by ultraviolet spectroscopy and by electron spin resonance (ESR) . Consumption of GSH was measured by amperometric titration . One or two moles of GSH was oxidized per mole of H2O2 added, depending on the reaction conditions . Omission of SCN- prevented the oxidation of GSH . The oxidation of GSH required only catalytic amounts of SCN-, which was therefore recycled . Iodide (I-) could replace SCN-, while chloride or bromide were ineffective . The apparent Michaelis constant for SCN- was 17 microM . Oxidation of SCN- gave rise to two reactive intermediates, one stable and one unstable . The stable intermediate (-OSC . = N-(?)) decayed by a second-order reaction with a rate constant of 1.1 M-1 s-1 . The decay of the unstable radical was very fast . The data (a) explain the short- and long-term antibacterial effects of lactoperoxidase-halide-H2O2 system, (b) point to possible deleterious effects due to glutathione depletion, (c) are of relevance for free radical diseases involving sulphur-centered free radicals, and (d) support previous observations on lipid peroxidation/halogenation in biological membranes, liposomes, and unsaturated fatty acids.

J Marmara Univ Dent Fac, 1992 Sep, 1(3), 237 - 49
Antibacterial effects of ofloxacin, clindamycin and sultamicillin on surgical removal of impacted third molars; Goker K et al.; This study examined the bacteraemia following surgical removal of impacted mandibular third molars and evaluated the antibacterial effects of Ofloxacin, Clindamycin, Sultamicillin, used as prophylactic medications . The study involved a hundred healthy patients whose mandibular third molars were impacted horizontally . These patients were divided into four groups each including 25 individuals . One of the four groups was the control group . The other groups were those to which Ofloxacin, Clindamycin, and Sultamicillin were administered one hour before the operation and in the following 4 days postoperatively . Blood samples were taken before and immediately after the operation, and then, 1 and 24 hours postoperatively . Following the incubation of the samples under aerobic and anaerobic conditions, the samples were examined microbiologically . Preoperative samples were found to be negative . In the immediate postoperative samples, bacteraemia was found in 44% of the control group, 40% of Ofloxacin and Clindamycin groups and 36% of the Sultamicillin group . In the samples taken 1 hour after the operation, bacteraemia was found in 28% of the control group, 20% of the Ofloxacin group and 24% of the Clindamycin and Sultamicillin groups . In the control group, only 2 cases showed positive culture in the blood samples taken 24 hours after the operation . In conclusion, the antibiotics, Ofloxacin, Clindamycin, Sultamicillin have a significant effect in decreasing the risk of postoperative infection and bacteraemia.

Gaoxiong Yi Xue Ke Xue Za Zhi, 1992 Sep, 8(9), 471 - 6
{Phagocytosis of the reticuloendothelial system in diabetes mellitus}; Wang SJ et al.; It has been assumed that patients with diabetes mellitus (DM), who are usually susceptible to bacterial infections, have a depression of the antibacterial defense mechanism . This study was undertaken to substantiate the hypothesis that phagocytosis of the reticuloendothelial system (RES) is depressed in diabetic patients . It is believed that intravenously injected colloidal suspensions whose particles are unable to pass through the capillary barrier will be phagocytized mainly by the reticuloendothelial cells in the liver and spleen . In the present study, the RES phagocytic index (RESPI) was measured in 48 subjects: 20 normal controls and 28 patients with DM . Measurements were based on the rate of disappearance (T1/2) of radioactivity in the heart (blood pooling) after rapid I.V . injection of 3mCi of Tc-99m phytate (2mg phytate) . Using a gamma camera, sequential images of the liver and heart were obtained, and computer-generated time-activity curves were established . The T1/2 was then calculated . Our results revealed that the RESPI values in the DM group were significantly increased as compared to the normal control group (normal control = 4.60 +/- 1.01; DM = 6.78 +/- 3.83; P < 0.05) . This prolonged half-disappearance time of blood radioactivity in diabetic patients is interpreted as a reflection of impaired phagocytotic efficiency in the reticuloendothelial system . The results of this preliminary study add support to the in vivo evidence explaining the increased susceptibility to infection in diabetic patients.

J Clin Invest, 1992 Aug, 90(2), 447 - 55
Peptides related to the carboxyl terminus of human platelet factor IV with antibacterial activity; Darveau RP et al.; A peptide (C13) corresponding to the last 13 amino acids of the carboxyl terminus of human platelet factor IV was found to be antibacterial . Amino acid substitutions predicted to disrupt either the amphipathic or alpha-helical nature of C13 rendered the peptide inactive . Antibacterial activity was demonstrated in normal human serum on bacteria which had been previously exposed to low levels of cefepime, a beta-lactam antibiotic . Peptide analogues were examined for more potent antibacterial activity in an antibacterial assay that employed normal human serum and low levels of cefepime . A peptide analogue (C18G) with 80-fold more antibacterial activity than C13 was identified . Studies in C8-deficient sera confirmed an essential role of human serum complement for optimal antibacterial activity . Additional studies showed low levels of cefepime, although not essential, enhanced the antibacterial activity of C18G . Animal protection experiments demonstrated that either peptide C18G or an analogue with all D amino acids (C18X) significantly increased the survival of neutropenic mice when coadministered with a low level of cefepime . This work has resulted in the identification of a new group of antibacterial peptides.

J Otolaryngol, 1992 Aug, 21(4), 290 - 2
Tuberculous mastoiditis; Chernoff WG et al.; The prevalence of Mycobacterium tuberculosis is increasing due in part to the rising incidence of immunocompromised hosts . Although Mycobacterium tuberculosis is a well-documented pathogen in otitis media and mastoiditis, its extremely low incidence often precludes consideration when treating these infections . This is especially true when concomitant pulmonary symptoms are absent . We describe two patients who initially presented after prolonged unsuccessful medical and surgical therapy for chronic mastoiditis . In both, the diagnosis of Mycobacterium tuberculosis mastoiditis was made after the onset of complete facial paralysis . On subsequent investigations, one had an asymptomatic pulmonary focus while the other was felt to have primary mastoid disease . Both patients had normal immunological profiles . This report underscores the importance of considering a tuberculous infection in all cases of otitis media and mastoiditis which do not initially respond to conventional antibacterial therapy . This holds true in both immunocompromised and immunocompetent hosts . Early diagnosis with prompt institution of antituberculous therapy is essential to avoid facial nerve paralysis and other grave complications.

Appl Environ Microbiol, 1992 Aug, 58(8), 2559 - 64
Effects of antibacterial agents on in vitro ovine ruminal biotransformation of the hepatotoxic pyrrolizidine alkaloid jacobine; Wachenheim DE et al.; Ingestion of pyrrolizidine alkaloids, naturally occurring plant toxins, causes illness and death in a number of animal species . Senecio jacobaea pyrrolizidine alkaloids cause significant economic losses due to livestock poisoning, particularly in the Pacific Northwest . Some sheep are resistant to pyrrolizidine alkaloid poisoning, because ovine ruminal biotransformation detoxifies free pyrrolizidine alkaloids in digesta . Antibacterial agents modify ruminal fermentation . Pretreatment with antibacterial agents may account for some animal variability in resistance to pyrrolizidine alkaloid toxicosis, and antibacterial agents can also be used for characterizing ruminal pyrrolizidine alkaloid-biotransforming microflora . The objective of this study was to evaluate the effects of antibacterial agents on biotransformation of a predominant S . jacobaea pyrrolizidine alkaloid, jacobine, in ovine ruminal contents . Ovine ruminal jacobine biotransformation was tested in vitro with 20 independent antibacterial agents . Low amounts of rifampin and erythromycin prevented jacobine biotransformation . Chlortetracycline, lasalocid, monensin, penicillin G, and tetracycline were slightly less effective at inhibiting jacobine biotransformation . Bacitracin, crystal violet, kanamycin, and neomycin were moderately inhibitory against jacobine biotransformation . Brilliant green, chloramphenicol, gramicidin, nalidixic acid, polymyxin B SO4, sodium azide, streptomycin, sulfisoxazole, and vancomycin had little to no effect on jacobine biotransformation . The antibiotics that were most effective at inhibiting biotransformation were those that are active against gram-positive bacteria . Therefore, gram-positive bacteria are most likely critical members of the jacobine-biotransforming consortia.

Curr Opin Oncol, 1992 Aug, 4(4), 614 - 23
Supportive care in marrow transplantation; Bensinger WI; Marrow transplantation is now an accepted form of therapy for patients with aplastic anemia, genetic diseases, and a variety of malignant diseases . Intensive chemotherapy and radiotherapy regimens are necessary to eradicate cancer cells and allow engraftment of the transplanted marrow . Patients undergoing such treatment suffer prolonged marrow aplasia and immunosuppression and experience significant nonmarrow toxicities . This requires maximum supportive care including hyperalimentation, fluid and blood transfusions, antibacterial and antiviral prophylaxis, and measures to reduce organ toxicities and accelerate engraftment . The use of drugs to suppress the production of antitumor necrosis factor-alpha has shown promise in reducing the nonmarrow toxicities of the conditioning regimen . Prophylactic antibiotics that reduce gastrointestinal colonization with aerobic bacteria yet preserve anaerobic flora may more effectively reduce not only systemic bacteria but fungal infections as well . The impact of infections due to cytomegalovirus has been reduced by more effective prevention in patients who are cytomegalovirus negative and reactivation in patients who are cytomegalovirus positive . The use of recombinant growth factors will significantly reduce morbidity after transplantation by reducing the period of marrow aplasia.

J Vasc Surg, 1992 Aug, 16(2), 251 - 7
A prospective randomized evaluator-blinded trial of two potential wound healing agents for the treatment of venous stasis ulcers; Bishop JB et al.; Chronic wounds such as venous stasis ulcers have become a socioeconomic problem . Even with successful initial management, the recurrence rate approaches 70% . With the advent of new wound healing agents, nonoperative attempts to heal these wounds appear indicated . This study reports a prospective randomized evaluator-blinded trial comparing two potential wound healing agents to an inert vehicle placebo . Eighty-six evaluable patients completed the trial . Silver sulfadiazine 1% in a cream proved to statistically reduce the ulcer size compared with a biologically active tripeptide copper complex 0.4% cream formulation or the placebo . There was no difference between the latter two treatments . Silver sulfadiazine has been shown to allow keratinocyte replication and to have antiinflammatory properties . In this trial its antibacterial action was not used since all ulcers had comparable bacterial levels (less than or equal to 10(5)/gm of tissue) before treatment . These results suggest that the silver sulfadiazine cream used in this study may facilitate healing in wounds healing largely by the process of epithelialization.

Antibiot Khimioter, 1992 Aug, 37(8), 14 - 5
{Experience with using cefoperazone in cancer patients after bone marrow transplantation}; Afanas'ev BV et al.; Cefoperazone is a semisynthetic cephalosporin of the 3rd generation (cefobid, Pfizer, USA) . It was used in monotherapy of 12 oncological patients during ++post-cytostatic aplasia of the bone marrow and peripheral pancytopenia after bone marrow transplantation . The results were favourable in 67 per cent of the patients: the body temperature normalized and no signs of any infection were evident . In 25 per cent of the patients the monotherapy failed and it was necessary to combine cefoperazone with aminoglycosides . Therefore, cefoperazone proved to be an efficient antibacterial drug, whose use was possible in the monotherapy of oncological patients after transplantation of the bone marrow.

Pharmazie, 1992 Aug, 47(8), 623 - 6
{Activity of new iminium compounds against bacteria and fungi . 28 . Synthesis of 1-ethyl-, 1-n-dodecyl-2-phenyl-3-(n-alkylthiomethyl)- and 1-ethyl-, 1-n-dodecyl-2-phenyl-3-(n-alkoxymethyl)imidazolium chlorides}; Pernak J et al.; The synthesis of quaternary imidazolium compounds was performed by reaction of 1-ethyl- or 1-n-dodecyl-2-phenylimidazole with chloromethyl-n-alkyl ether or chloromethyl-n-alkyl sulfid . The antibacterial properties of the compounds obtained were tested on 13 strains of bacteria and fungi . 1-Ethyl-2-phenyl-3-(n-decylthiomethyl)-, 1-ethyl-2-phenyl-3-(n-dodecylthiomethyl)imidazolium chloride and 1-n-dodecyl-2-phenyl-3-(n-butylthiomethyl)-, 1-n-dodecyl-2-phenyl-3-(n-hexylthiomethyl)imidazolium chloride indicated the best antibacterial activity.

Arch Pharm (Weinheim), 1992 Aug, 325(8), 455 - 9
{Actions of new iminium compounds on bacteria and fungi . 27 . Synthesis of 1-n-decyl-2-phenyl-3-(n-alkylthiomethyl)- and 1-n-decyl-2-phenyl-3-(n-alkoxymethyl)imidazolium chlorides}; Pernak J et al.; The imidazolium compounds 1-3 were prepared by quaternization of 1-decyl-2-phenylimidazole with the pertinent chloromethyl-n-alkyl ethers . 1-3 were tested for their antibacterial and antimycotic efficacies.

J Pediatr Gastroenterol Nutr, 1992 Aug, 15(2), 150 - 8
Inhibition of adhesion of S-fimbriated Escherichia coli to epithelial cells by meconium and feces of breast-fed and formula-fed newborns: mucins are the major inhibitory component; Schroten H et al.; We investigated the ability of meconium, feces from human milk-fed (HMF) newborns, and feces from formula-fed (FF) newborns to inhibit adhesion of S-fimbriated E . coli to human buccal epithelial cells . S-fimbriae are a common property of E . coli strains causing sepsis and meningitis in neonates . Meconium had the highest content of neuraminic acid and the strongest inhibitory effect on bacterial adhesion . HMF also exerted high inhibitory activity while FF was markedly less active: To achieve inhibitory effects comparable to HMF a sixfold amount of FF was required . Glycoproteins from excretions were separated by gel chromatography . Fractions obtained were analyzed for adhesion-inhibiting activity . In all excretions analyzed, the mucin-containing fraction could be identified as the major inhibitory component . Inhibition was probably mediated by specific interaction of this fraction with S-fimbriae, as shown by binding of isolated fimbriae on Western blots after electrophoretic separation of glycoproteins . In conclusion, our data support the view that the mucin-containing fraction from meconium and human milk exerts antibacterial functions by preventing adhesin-mediated binding of pathogenic bacteria to mucosal epithelia.

Antimicrob Agents Chemother, 1992 Aug, 36(8), 1715 - 9
Photostability and biological activity of fluoroquinolones substituted at the 8 position after UV irradiation; Matsumoto M et al.; Q-35 {1-cyclopropyl-6-fluoro-1,4-dihydro-8-methoxy-7-(3-methylaminopiperid ine-1-yl)-4-oxoquinoline-3-carboxylic acid}, a fluoroquinolone, has absorbance peaks at 333 and 286 nm . No spectral change was observed even when this aqueous solution was irradiated with 3 J of long-wavelength UV light (UVA) per cm2 . On the other hand, its derivatives, which are unsubstituted (8-H analog) or which are substituted with fluorine at the 8 position (8-F analog), were found to have decreased antibacterial activities with a simultaneous increase in their cytotoxicities when they were degraded in a dose-dependent manner with respect to UVA irradiation . Similar results were observed with the other available fluoroquinolones . Enoxacin and lomefloxacin exposed to 0.3 J of irradiation per cm2 and norfloxacin, ofloxacin, and ciprofloxacin exposed to 1 J of irradiation per cm2 underwent absorption spectrum changes, an accompanying decrease in antibacterial activity, and an increase in cytotoxic activity . These results suggest that the introduction of a methoxy group into the 8 position of quinolones plays an important role in the stability of fluoroquinolones against irradiation by UV light.

Kinderarztl Prax, 1992 Aug, 60(6), 159 - 62
{Complications of acute respiratory tract infection (pneumonia, sinusitis) in young children associated with acute HHV 6 infection}; Wiersbitzky S et al.; The human herpesvirus-6 (HHV-6) causes exanthema subitum ("e.s.") . "E.s." is characterized by fever, exanthem (rash), in many cases gastroenteritis, occasionally cerebral convulsions (but more frequently general cerebral irritability) and enlargement of all lymph nodes; usually there are mild catarrhal respiratory symptoms of the upper airways (ARD) . So-called "complications" of an ARD (pneumonia, acute purulent otitis media, acute sinusitis) due to bacterial infections are very unusual as sequelae of a HHV-6 infection . Here we report the case of 2 small children (toddlers) suffering from bronchopneumonia or pneumonia and acute sinusitis maxillaris associated with an acute HHV-6 infection . It seems that HHV-6 (like other respiratory tract viral pathogens) also can lead to secondary bacterial infections of the lower respiratory tract . So far it is not known, why such complications are so rare, although the extreme granulocytopenia accompanying "e.s." suggests a transient disturbance of the antibacterial defence mechanisms.

J Biol Chem, 1992 Jul 25, 267(21), 14955 - 62
Bacterial lipopolysaccharide induces tyrosine phosphorylation and activation of mitogen-activated protein kinases in macrophages; Weinstein SL et al.; Bacterial lipopolysaccharide (LPS) is a potent activator of antibacterial responses by macrophages . Following LPS stimulation, the tyrosine phosphorylation of several proteins is rapidly increased in macrophages, and this event appears to mediate some responses to LPS . We now report that two of these tyrosine phosphoproteins of 41 and 44 kDa are isoforms of mitogen-activated protein (MAP) kinase . Each of these proteins was reactive with anti-MAP kinase antibodies and comigrated with MAP kinase activity in fractions eluted from a MonoQ anion-exchange column . Following LPS stimulation, column fractions containing the tyrosine phosphorylated forms of p41 and p44 exhibited increased MAP kinase activity . Inhibition of LPS-induced tyrosine phosphorylation of these proteins was accompanied by inhibition of MAP kinase activity . Additionally, induction of p41/p44 tyrosine phosphorylation and MAP kinase activity by LPS appeared to be independent of activation of protein kinase C, even though phorbol esters also induced these responses . These results demonstrate that LPS induces the tyrosine phosphorylation and activation of at least two MAP kinase isozymes . Since MAP kinases appear to modulate cellular processes in response to extracellular signals, these kinases may be important targets for LPS action in macrophages.

J Med Chem, 1992 Jul 24, 35(15), 2898 - 909
Fluoronaphthyridines as antibacterial agents . 6 . Synthesis and structure-activity relationships of new chiral 7-(1-, 3-, 4-, and 6-methyl-2,5-diazabicyclo{2.2.1}heptan-2-yl)naphthyridine analogues of 7-{(1R,4R)-2,5- diazabicyclo{2.2.1}heptan-2-yl}-1-(1,1-dimethylethyl)-6-fluoro-1,4-dihy dro-4-oxo-1,8-naphthyridine-3-carboxylic acid . Influence of the configuration on blood pressure in dogs . A quinolone-class effect; Remuzon P et al.; A series of novel chiral 7-(1-, 3-, 4-, and 6-methyl-{(1R,4R)-2,5- diazabicyclo{2.2.1}heptan-2-yl}-substituted naphthyridines has been prepared with the aim of obtaining good in vitro and in vivo antibacterial agents with a decrease of the pseudoallergic type reaction when compared to that observed with 7{(1R,4R)-2,5-diazabicyclo{2.2.1}heptan-2-yl}-1-(1,1-dimethylethyl )1,4- dihydro-6-fluoro-4-oxo-1,8-naphthyridine-3-carboxylic acid (1a) (BMY 40062) . The derivatives 7-{(1R,4R,6S)-6-methyl-2,5-diazabicyclo{2.2.1}heptan-2-yl}- 1-(1,1-dimethylethyl)-6-fluro-1,4-dihydro-4-oxo-1,8-naphthyridine- 3-carboxylic acid (41) and 7-{(1R,4R,6S)-6-methyl-2,5-diazabicyclo{2.2.1}heptan-2- yl}-1-cyclopropyl-6-fluoro-1,4-dihydro-4-oxo-1,8-naphthyridine-3-carboxy lic acid (49) showed potent in vitro and in vivo antibacterial activity against Gram-positive and Gram-negative bacteria . The derivative 49 displayed a less marked decrease in blood pressure (MAP), compared to that of 1a, after intravenous infusion in dogs and was selected as a potential candidate for preclinical trials.

J Med Chem, 1992 Jul 10, 35(14), 2643 - 51
Pharmacokinetics of catechol cephalosporins . The effect of incorporating substituents into the catechol moiety on pharmacokinetics in a marmoset model; Bird TG et al.; Two series of cephalosporins A and B have been synthesized, bearing at C-3' catechols substituted with various electron withdrawing groups (Y) and differing links (X), and were evaluated for their in vitro antibacterial activity and their pharmacokinetics in marmosets . Compounds in series A, bearing an isobutyric oxime substituent, proved to be highly active against Gram-negative organisms and were especially noteworthy for showing long elimination phase (beta) half-lives in marmosets . It was established that introduction of electron withdrawing substituents greatly increased the beta half-lives of compounds (5, X = NHCO, Y = H, t1/2 = 1.25 h, AUC = 27 mg/h per L; 11, X = NHCO, Y = 5-Cl, t1/2 = 4.5 h, AUC = 638 mg/h per L) and that the nature of the link also influenced t1/2, the highest values being obtained when X = NHCO and OCO . Acidities (pKa values) of the substituted catechols were measured, and relationships between the acidities and half-lives were evaluated . Thus it was established that the more acidic catechols gave the longest half-lives (12, X = NHCO, Y = 2,5-Cl2, t1/2 = 8.2 h, AUC = 461 mg/h per L) . Further elaboration of the catechol to bicyclic systems maintained good pharmacokinetics when the pKa was sufficiently acidic.

Drug Saf, 1992 Jul-Aug, 7(4), 268 - 81
Drug interactions with quinolone antibacterials; Brouwers JR; The quinolone antibacterials are prone to many interactions with other drugs . Quinolone absorption is markedly reduced with antacids containing aluminium, magnesium and/or calcium and therapeutic failure may result . Other metallic ion-containing drugs, such as sucralfate, iron salts, and zinc salts, can also reduce absorption . Some of the newer quinolones inhibit the cytochrome P450 system, e.g . enoxacin, pefloxacin and ciprofloxacin . The toxicity of drugs that are metabolised by the cytochrome P450 system is enhanced by concomitant use of some quinolones . Ciprofloxacin, enoxacin and pefloxacin can increase theophylline concentrations to toxic values . The pharmacokinetics of warfarin and cyclosporin are unaffected . Ofloxacin, fleroxacin and temafloxacin have a low inhibitory effect on the cytochrome P450 system and a low interaction potential may result . The affinity of quinolones for the gamma-aminobutyric acid (GABA) receptor may induce CNS adverse effects; these effects are enhanced by some nonsteroidal anti-inflammatory drugs (NSAIDs).

J Dairy Sci, 1992 Jul, 75(7), 1810 - 20
Nonspecific antibacterial factors in milk from cows immunized with human oral bacterial pathogens; Takahashi N et al.; Both the immunoglobulins and non-specific antibacterial factors in milk from cows immunized with pathogenic oral bacteria have the potential to influence the oral microflora during passive immunization studies . The first six milks after calving were collected from 2 cows immunized with adjuvant and from 14 cows immunized with adjuvant and heat-killed strains of periodontopathic Actinomyces, Porphyromonas, Prevotella, and Fusobacterium . Analysis of the products from the first to the sixth milks revealed that the protein and lysozyme content decreased approximately 66 and 72%, respectively; the mean specific activity of the enzyme remained relatively constant . In contrast, the mean lactoperoxidase activity increased 2.3-fold in the second milking and increased further in the fourth and sixth milkings . The mean iron-binding activity increased 1.2-fold from the first to the second milkings and then decreased 3.6-fold through the sixth milking . Cows immunized with adjuvant alone showed similar responses . Per unit volume, the milk contained approximately 150 times less lysozyme than whole human saliva obtained from six subjects but higher concentrations of lactoperoxidase and iron-binding components . Purified bovine nonspecific factors prevented the growth of the bacteria used for immunization when bacteria were tested at concentrations similar to those found in saliva and milk . Because bovine nonspecific antibacterial factors could influence both the pathogenic target bacteria and the indigenous microflora in oral passive immunization studies with bovine immunoglobulins, the presence of these proteins should be considered.

Laryngorhinootologie, 1992 Jul, 71(7), 365 - 9
{Perioperative single dose prevention with cephalosporins in the ENT area . A prospective randomized study}; Maier W et al.; Perioperative systemic antibiotic cover is usually recommended in major head and neck surgery with the aim of preventing postoperative wound infection . The surgeon must administer the drug most suitable for the particular operation and patient at an adequate dosage and over an adequate period . On the other hand, he has an obligation to minimize costs and find ways of avoiding the development of bacterial resistance to the antibiotic . This means that prophylactic antibiotics may not have too broad an antibacterial spectrum and may only be used over the short term . In an attempt to improve antibiotic prophylactic in head and neck surgery, we tested the effectiveness of a perioperative single-dose antibiotic cover with cefuroxim (Zinacef) in patients undergoing parotidectomy, sinus surgery or neck dissection with no transcutaneous exploration of the pharynx . This single-shot prophylaxis was compared with a three-shot, 24-hour regimen using the same antibiotic . The two regimens were equally effective in preventing wound infection and no case of infection was observed among the 106 patients involved . Preoperative concentrations of cefuroxim were measured in serum and tissue, and the large majority of specimens showed effective concentrations against the typical wound infection bacteria . In conclusion, a perioperative single-dose administration of cefuroxim proved to be suitable prophylaxis against postoperative wound infection in head and neck surgery.

Lik Sprava, 1992 Jul, (7), 56 - 61
{The clinico-physiological validation of the use of the endolymphatic route for antibiotic administration for preventing the translocation of intestinal microflora during the treatment of sepsis patients}; Maksimenko VI et al.; One of the main mechanisms of generalization of infection in purulent-inflammatory processes of the abdominal cavity, retroperitoneal space and pelvis minor is translocation of the pathogenic microflora of the intestine in the lymphatic system via regional lymphatic nodes with subsequent rupture into the systemic circulation . Endolymphatic administration of antibacterial agents into the peripheral lymphatic vessel favours saturation of the reticuloendothelial structures of the lymph nodes by the antibiotic agent that increases their barrier function and, thus, prevents generalization of the infection and development of polyorganic insufficiency.

Lik Sprava, 1992 Jul, (7), 33 - 7
{The efficacy of antibacterial treatment in chronic gastritis of Helicobacter etiology}; Medvedev VN et al.; A study of 140 patients with chronic gastritis revealed Helicobacter pylori in the gastric antral mucosa in 100% and in the duodenum in 50% . There is a direct correlation between the presence and amount of Helicobacter pylori in the mucosa, lymphoplasmocytic infiltration, dystrophic changes of epithelium . Ampiox treatment proved beneficial both clinically and morphologically . After treatment Helicobacter pylori was absent in 65.7%, in the remaining cases it reduced by 5-10 times.

Avian Dis, 1992 Jul-Sep, 36(3), 688 - 92
Effects of ascorbic acid on stress and disease in chickens; Gross WB; White leghorn chickens were given feed containing 100 mg of ascorbic acid (AA)/kg . One day later, treated chickens and a similar group of unmedicated control chickens were chilled for 1 hour at 6 C, exposed to an unusual sound, fasted, or subjected to rough handling . Heterophil:lymphocyte (H:L) ratios were determined one day later . The AA-treated birds had significantly lower H:L ratios than untreated controls . Chickens that received a diet containing AA had lower H:L ratios than controls (0.86 vs . 1.65) following administration of adrenocorticotropic hormone . Chickens fed a diet containing AA showed increased resistance to a combined Newcastle disease virus-Mycoplasma gallisepticum infection and to a secondary Escherichia coli infection, as well as to a primary E . coli challenge infection . The effects of AA and an antibacterial drug (furaltadone) were additive . In all experiments, the optimum dose of AA was 100 mg/kg of feed . There was a negative correlation between AA level in the diet and feed efficiency.

J Antimicrob Chemother, 1992 Jul, 30 Suppl A, 77 - 81
In-vitro activity of RP 59500, a new synergic antibacterial agent, against Legionella spp; Dubois J et al.; The in-vitro activity of RP 59500, a new semisynthetic injectable streptogramin, was compared with that of erythromycin, rifampicin and ciprofloxacin against 189 Legionella spp . Rifampicin was the most active agent tested . RP 59500 was found to be more active than erythromycin against most strains, but less active than ciprofloxacin . Legionella pneumophila serogroups 1, 3, 4, 5 and 6 were more susceptible to RP 59500 than were L . pneumophila serogroups 2, 7, and 8 . Legionella micdadei was the least susceptible species to RP 59500 and erythromycin . RP 59500 was similar in activity against isolates obtained from both patients and environmental sources . This activity was generally better than that of erythromycin.

Arch Int Physiol Biochim Biophys, 1992 Jul-Aug, 100(4), A41 - 6
{Structure and secretory functions of the respiratory epithelium}; Jacquot J et al.; Airway secretions actively participate in respiratory epithelium protection . Apart from its main participation in transport of inhaled microorganisms and particles by mucociliary clearance, respiratory mucus also contributes to other protective purposes such as the control of airway humidification . Biochemical components found in secretions, such as mucins, lipids, antibacterial agents (secretory IgA, lysozyme, lactoferrin), antioxidant and antiprotease components, contribute significantly to the airway epithelium defense.

Minerva Chir, 1992 Jun 30, 47(12), 1095 - 9
{Antibiotic prophylaxis in surgery . Results of a 4-year personal case series}; Gerosa E et al.; A prospective study of surgical infections in our Department of Surgery in the years 1986-1989 is reported . 2719 patients entered the study: they represent the total number of patients operated in the above said period (628 urgent and 2091 elective operations) . As suggested in 1964 by Altmeier, surgical procedures were classified in four groups according to the potential risk of intraoperative contamination . For every septic complication observed pertinent cultures were performed and responsible pathogens identified . We present our protocol of antibacterial prophylaxis which distinguishes antibiotics given as "ultra short term", "short term", "antibiotic prophylaxis" . The results obtained and particularly the total number of infections (3.9%), and the percentage of infections in group 3 (4.6%) and in group 4 (23.1%) procedures validate the usefulness of antibiotic prophylaxis in these patients . In group 1 and group 2 patients the usefulness of antibiotic prophylaxis seems very doubtful.

J Am Vet Med Assoc, 1992 Jun 1, 200(11), 1692 - 4
Conservative management of uroperitoneum in a gelding; Gibson KT et al.; Uroperitoneum as a sequela to urethral calculus in an adult gelding was successfully managed by use of subischial urethrotomy and abdominal drainage . Necrosis of bladder mucosa was seen endoscopically, but a tear or rupture was never identified . Peritonitis developed but was controlled with antibacterial treatment . Although uroperitoneum is usually a sequela to bladder rupture and the ideal treatment is surgical repair, conservative management may be warranted in selected cases.

Clin Infect Dis, 1992 Jun, 14 Suppl 2, S233 - 7; discussion S244-5
Antibacterial therapy for lower respiratory tract infections in adults: a review; LaForce FM; Because of difficulties in accurately determining an etiologic diagnosis, the ideal treatment for acute community-acquired lower respiratory tract infections remains to be established . Suggested regimens, in the absence of persuasive findings from gram-stained preparations of sputum, are best guesses made on the basis of clinical and epidemiological data . Results from randomized controlled trials are only partially helpful since most trials require the isolation of a potential pathogen, a condition that excludes as many as half of all potential study participants . Nonetheless, initial therapy for patients producing phlegm with abundant polymorphonuclear leukocytes should be chosen on the basis of the predominant organisms seen on a stained sputum smear . Patients who are admitted to the hospital from home, greater than 50 years of age, and not producing phlegm can be safely treated with amoxicillin or a second-generation cephalosporin . Atypical pneumonia in younger patients is best treated with erythromycin or tetracycline . Patients admitted from nursing homes, who frequently fail to respond to an initial treatment course in the absence of a diagnostic sputum sample, should receive empirical therapy with an agent that is also active against aerobic gram-negative rods.

FEBS Lett, 1992 Jun 1, 303(2-3), 265 - 8
The antibacterial peptide seminal plasmin alters permeability of the inner membrane of E . coli; Sitaram N et al.; Seminal plasmin (SPLN) a 47-residue peptide, isolated from bovine seminal plasma, exhibits antibacterial activity against Gram-positive and Gram-negative bacteria . Although SPLN strongly inhibits the transcription of various natural and synthetic templates by E . coli RNA polymerase in vitro, it also associates with model membranes of phosphatidylcholine and phosphatidic acid . We have undertaken experiments to ascertain whether SPLN permeabilizes the bacterial inner membrane and thereby exerts its antibacterial activity, as in the case of recently isolated antibacterial peptides from mammalian sources . Our results show that SPLN affects the permeability properties of the bacterial inner membrane which is reflected by increased uptake of ortho-nitrophenylgalactoside (ONPG), which can normally be translocated only by protein transporters . SPLN has also been shown to act on the outer membrane, since divalent cations inhibit antibacterial activity.

J Antibiot (Tokyo), 1992 Jun, 45(6), 940 - 53
Synthesis and in vitro activity of novel quaternary ammonium carbapenems: 2-pyridiniopropyl and 1-pyridinioethyl carbapenems; Ueda Y et al.; The synthesis of new carbapenems having either a pyridiniopropyl group at the 2-position or a pyridinioethyl group at the 1-position is described, along with the preparation of their corresponding hydroxy and acetoxy analogs . The antibacterial activity, susceptibility to dehydropeptidase-I (DHP-I) enzyme and chemical stability of these new carbapenems are also reported . 2-Pyridiniopropyl-carbapenem 4 was found to possess excellent antibacterial activity . It was more stable chemically and less susceptible to the DHP-I enzyme than the thio analog 3 . 1-Pyridinioethylcarbapenem 5 showed significantly reduced antibacterial activity as compared to 2-pyridiniopropylcarbapenem 4.

Planta Med, 1992 Jun, 58(3), 266 - 9
Acetylenic glucosides from Microglossa pyrifolia; Rucker G et al.; From the leaves of Microglossa pyrifolia Lam . (Asteraceae) four new acetylenic glucosides (1-4) have been isolated . The aglucones 2a and 4a are new polyynes . The aglucone 3a could only be isolated as a mixture of E/Z-isomers in a ratio of 4:1 . The structures of 1-4 were elucidated by spectroscopic and biochemical methods . Compound 1 shows antibacterial activity.

J Inorg Biochem, 1992 Jun, 46(4), 251 - 7
Synthesis, characterization, and antibacterial activity of transition metal complexes with 5-hydroxy-7,4'-dimethoxyflavone; Wang SX et al.; Complexes of CuII, NiII, CoII, ZnII, FeIII, CrIII, CdII, and MnII with the natural product 5-hydroxy-7,4'-dimethoxyflavone have been synthesized and the probable structures of these complexes have been proposed on the basis of elemental analyses, molecular weight determination, magnetic moments, and electronic and IR spectral data . The presence of coordinated and crystal water molecules was demonstrated by thermal studies . The antibacterial activity of the ligand and all the complexes has been determined on gram positive and gram negative bacteria.

Chem Pharm Bull (Tokyo), 1992 Jun, 40(6), 1537 - 9
Biopolymers from marine invertebrates . XIII . Characterization of an antibacterial protein, dolabellanin A, from the albumen gland of the sea hare, Dolabella auricularia; Kisugi J et al.; An antibacterial factor, dolabellanin A, was purified from the albumen gland of a sea hare, Dolabella auricularia . Purified dolabellanin A was a glycoprotein of 250 kilodaltons consisting of 4 subunits, and showed both antibacterial and antineoplastic activities . The two activities were lost in parallel on heating and at low and high pH . This factor was half-maximally active for gram-positive and -negative bacteria at 0.018-0.48 microgram/ml, and its action was not bactericidal but bacteriostatic . Dolabellanin A did not induce morphological elongation of bacteria or the release of adenosine triphosphate, but it completely inhibited the syntheses of deoxyribonucleic acid (DNA) and ribonucleic acid by E . coli within 6 min . These results suggest that dolabellanin A, which is found in a marine invertebrate, the sea hare, is a new antibacterial protein, and that it exerts its action by inhibiting nucleic acid synthesis, as does a DNA-inhibiting chemotherapeutic drug.

Farmaco, 1992 Jun, 47(6), 979 - 83
Condensation products of 2-amino-3-cyano-4,6-disubstituted pyridine with carbon disulfide, thiourea, urea & formamide and their antibacterial activity; Gupta A et al.; Some new 5,7-disubstituted pyrido{2,3-d}pyrimidine derivatives have been synthesized by the condensation of 2-amino-3-cyano-4,6-disubstituted pyridine with carbon disulfide, thiourea, urea and formamide . The structure of these products are supported by their IR and 1H-NMR spectra as well as by elemental analysis . The compounds have been tested for their antibacterial activity against E . coli and S . aureus.

Clin Ter, 1992 Jun, 140(6), 563 - 7
Ocular pharmacokinetics of rufloxacin a new fluoroquinolone antibiotic; Nucci P et al.; Ocular pharmacokinetics of rufloxacin (MF 934), a new monofluorinated quinolone derivative, has been investigated in rabbits . A long half-life, good g.i . absorption and a higher tissue/plasma concentration than that of other quinolones, are its interesting pharmacokinetic properties . However, there is reason to believe that drug accumulation may occur in deep body compartments . We determined plasma, aqueous, and vitreous concentrations of the drug at 1, 4, 8, and 24h after a single 50 mg/kg i.v . administration of rufloxacin . Our data show that rufloxacin, administered by the i.v . route, rapidly reaches chemotherapeutically useful levels in aqueous and vitreous fluids . Although still present in plasma 8 hours after administration, it proved to be undetectable in ocular fluids, signifying that the depletion of the deep compartments occurs well in advance of the next invasion . Due to its antibacterial effectiveness and pharmacokinetic properties rufloxacin may take a relevant place among the quinolone derivatives in the treatment of ocular infections.

Vet Rec, 1992 May 30, 130(22), 485 - 7
Chronic tracheobronchial syndrome in eight dogs; Corcoran BM et al.; Chronic tracheobronchial syndrome was diagnosed in eight dogs which had had a chronic mild cough for two to 13 months but were otherwise clinically normal . In five of them there was evidence of contact with other coughing dogs before the appearance of clinical signs and the majority at first responded favourably to antibacterial therapy . The coughing occurred mainly when the dogs pulled on their leads or became excited . Three cases had bronchoscopic evidence of active airway inflammation, and five had varying numbers of inflammatory cells (neutrophils) in bronchial aspirates . There was no evidence of excessive production of mucus in the airways of any of the dogs . Seven had an increased bronchial pattern on radiographs but only one of the dogs has developed chronic bronchitis.

J Med Chem, 1992 May 15, 35(10), 1897 - 914
Substrate specificity of isopenicillin N synthase; Huffman GW et al.; Highly purified isopenicillin N synthase (IPNS) from two sources (naturally occurring in Penicillium chrysogenum and that expressed in Escherichia coli via a cloned gene derived from Cephalosporium acremonium) have been isolated and utilized in vitro to test synthetic modifications of the natural substrate, (L-alpha-amino-delta-adipyl)-L-cysteinyl-D-valine (ACV) . A very sensitive procedure utilizing the ability of beta-lactams to induce the synthesis of beta-lactamase was employed to determine whether an ACV analogue could serve as a substrate for IPNS . A wide variety of amino and carboxyl terminal tripeptide substitutions were examined and found to elicit positive beta-lactamase induction profiles . However, none of these modifications were found to function as efficiently as a substrate as ACV . One of the beta-lactam products which was formed from the reaction of IPNS and the tripeptide analogue was independently synthesized and evaluated for antibacterial activity . Modification of the L-cysteine residue in the second position of ACV resulted in tripeptides that were unable to serve as substrates . Conversion of the D-valine residue in the third position of ACV to an aromatic amino acid or to a highly electronegative residue such as trifluorovaline resulted in elimination of substrate activity and creation of an inhibitor of the enzyme.

J Med Chem, 1992 May 15, 35(10), 1828 - 39
Dual-action penems and carbapenems; Corraz AJ et al.; Two new series of dual-action antibacterial agents were synthesized in which penems and carbapenems were linked at the 2'-position to quinolones through either an ester or a carbamate moiety . Potent, broad-spectrum antibacterial activity was observed for both classes of compounds, indicative of a dual-mode of action.

J Med Chem, 1992 May 15, 35(10), 1764 - 73
Quinolone antibacterial agents . Synthesis and structure-activity relationships of a series of amino acid prodrugs of racemic and chiral 7-(3-amino-1-pyrrolidinyl)quinolones . Highly soluble quinolone prodrugs with in vivo pseudomonas activity; Sanchez JP et al.; A series of amino acid prodrugs of racemic and chiral 7-(3-amino-1-pyrrolidinyl)-6-fluoro-1,8-naphthyridine-3-carboxylic acids, 1-cyclopropyl-6,8-difluoro-3-quinolinecarboxylic acids, 1-cyclopropyl-6-fluoro-3-quinolinecarboxylic acids, and 5-amino-1-cyclopropyl-6,8-difluoro-3-quinolinecarboxylic acids have been prepared and evaluated for comparative antibacterial activity . Compounds were prepared by acylation of the 3-amino group of the pyrrolidine with common amino acids using standard peptide chemistry . This series has been compared with the parent compounds for antibacterial activity in vitro and in vivo as well as for comparative solubility . The amino acid analogues were less active in vitro, but had equal or increased efficacy in vivo . Indeed, it was proven that these compounds, which were stable to acid and base under the reaction conditions for their preparation, were rapidly cleaved in serum to give the parent quinolones . The amino acid derivatives showed a 3-70 times improved solubility when compared to the parent compounds . The most active compound of the series was {S-(R*,R*)}-7-{3-{(2-amino-1-oxopropyl)-amino}-1-pyrrolidinyl}-1- cyclopropyl-6-fluoro-1,4-dihydro-4-oxo-1,8-naphthyridine-3-carboxylic acid (PD 131112).

Cancer Res, 1992 May 15, 52(10), 2818 - 22
Antitumor quinolones with mammalian topoisomerase II mediated DNA cleavage activity; Yamashita Y et al.; Ninety quinolones were evaluated to determine whether their ability to induce mammalian topoisomerase II mediated DNA cleavage in vitro correlated with their antitumor activity in vivo . Ten quinolones generated linear DNA at a yield of more than 10% of substrate supercoiled DNA in the mammalian topoisomerase II mediated DNA cleavage assay . All of these compounds showed a significant increase in life span (greater than 20%) in the murine leukemia P388 model . These antitumor quinolones have closely related structures: two halogens at C-6 and C-8; and cyclopropyl at N-1 of quinolone skeleton . In contrast, many analogues of the above quinolones, as well as new quinolones used clinically as an antibacterial drug, did not induce the cleavable complex in vitro or show antitumor activity in vivo . These findings indicate that quinolone derivatives can be a promising new class of antitumor agent targeting mammalian topoisomerase II.

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