Antibiot Khimioter, 1990 Nov, 35(11), 54 - 6 {Features of incorporation of several antibiotics into erythrocyte ghosts--a system of targeted delivery of chemotherapeutic drugs}; Zhumadilov ZhSh et al.; Features of incorporation of cefazolin, ampicillin, kanamycin and gentamicin into erythrocytic shadows in patients with abdominal diseases and apparently healthy persons during hypoosmotic hemolysis were studied . The highest percentage of kanamycin and gentamicin incorporation into the erythrocytic shadows was observed . The parameter of the antibiotic incorporation from the incubation fluid into the erythrocytic shadows depended on the antibiotic type and dose . Rather significant resistance of the erythrocytic carriers with incorporated gentamicin to possible desorption and excretion of the antibiotic from the shadows into the blood flow was revealed which made their use possible for target release of antibiotics in the liver. Eur Respir J, 1990 Nov, 3(10), 1114 - 6 Bronchial response to nebulized antibiotics in children with cystic fibrosis; Chua HL et al.; Nebulized antibiotics are being used increasingly in children with cystic fibrosis . We assessed the effect of nebulized antibiotic solutions of varying tonicity on lung function in 12 children aged 5-15 yrs with cystic fibrosis . Baseline forced expiratory volume in one second and (FEV1) was measured, followed by a single nebulization of normal saline (272 mosmol.kg-1), tobramycin (248 mosmol.kg-1), or ticarcillin (3,080 mosmol.kg-1) . All children received each of these, administered randomly, one per day . FEV1 was remeasured 5, 15 and 30 min after completion of the nebulization . Ticarcillin (mean fall 10.7% (SD 8.9)) caused a larger fall in FEV1 than normal saline (4.8% (4.3), p less than 0.05) . The fall in FEV1 for ticarcillin was greater than for tobramycin (1.2% (2.0), p less than 0.05) . Normal saline did not result in a significantly larger fall in FEV1 than tobramycin (p greater than 0.05) . Bronchoconstriction to ticarcillin persisted at 30 min . We conclude that nebulized antibiotics can affect lung function in children with cystic fibrosis if the solutions are hypertonic. Zhonghua Wai Ke Za Zhi, 1990 Nov, 28(11), 660 - 1, 702 {A lesson from abuse of antibiotics after open heart surgery}; Guo ZY; This paper reports 8 cases of pseudomembranous colitis, 2 cases of fungal infection and 15 cases of drug fever, all of which were caused by persistent use of large doses of antibiotics following open heart surgery . The clinical characteristics of these complications and the methods of treating them are discussed, and the rational preventive use of antibiotics is emphasized. Chem Pharm Bull (Tokyo), 1990 Nov, 38(11), 2997 - 3003 Fungal metabolites . IV . Synthesis of an antibiotic peptide, trichosporin B-V, from Trichoderma polysporum; Iida A et al.; The antibiotic icosapeptide trichosporin B-V, which was isolated from Trichoderma polysporum, was synthesized by assembling five peptide fragments via the N,N'-dicyclohexylcarbodiimide method . The synthesized peptide was identical with the natural one. Minerva Stomatol, 1990 Nov, 39(11), 943 - 5 {The interaction between antibiotic therapy and contraceptive drugs}; Moniaci D et al.; Although the interaction between antibiotics prescribed by the dentist and the estroprogestinics has been Known for some time, to reduce the effects of oral contraception, the dentist tends to underestimate this possible possible complication . In this review the antibiotics taken into consideration and their mechanism of interaction with the oral contraceptives are discussed . The dentist's approach towards a patient in fertile age is suggested . In conclusion the use of oral estroprogestinics as a contraceptive method is affirmed to be not an obstacle to the administration of antibiotics, but a thorough anamnesis and a cautious prescription, together with informing the patient of the risks is necessary. Mol Microbiol, 1990 Nov, 4(11), 1921 - 32 Molecular characterization of pmbA, an Escherichia coli chromosomal gene required for the production of the antibiotic peptide MccB17; Rodriguez-Sainz MC et al.; Microcin B17 (MccB17) is a peptide antibiotic produced by Escherichia coli strains harbouring plasmid pMccB17 . We have isolated two mutations that strongly reduce the production of MccB17 . These mutations, which map at 96 min on the E . coli chromosome, define a new gene that we have called pmbA . A chromosomal DNA fragment of about 13 kb, including the wild-type pmbA allele, was cloned into a mini-Mu plasmid vector . pmbA was located within the cloned DNA fragment by insertional mutagenesis and deletion analysis . The nucleotide sequence of a 1.7 kb DNA region containing the gene was determined . pmbA encodes a hydrophilic protein of 450-amino-acid residues with a predicted molecular size of 48375D, which was visualized in polyacrylamide gels . Protein profiles of cellular envelope and soluble fractions from cells with plasmids overproducing PmbA indicated that it is cytoplasmic . Physiological experiments suggested that pmbA mutants synthesize a molecule (pro-MccB17) able to inhibit DNA replication but unable to be released from cells . We propose that PmbA facilitates the secretion of the antibiotic by completing its maturation. Arzneimittelforschung, 1990 Nov, 40(11), 1250 - 9 Chronic intravenous toxicity of the new antibiotic cefpirome in monkeys; Horstmann G et al.; Chronic intravenous toxicity studies in monkeys were carried out with 3-{(2,3-cyclopenteno-1-pyridinium)-methyl}-7-{2-syn-methoximino - 2-(2-aminothiazol-4-yl)-acetamido}-ceph-3-em-4-carboxylate (cefpirome, HR 810; CAS 84957-29-9) a new cephalosporin derivative . In a 90-day study in rhesus monkeys (4 males/4 females per group) dosages of 0, 50, 160 and 500 mg/kg/day were administered . In a 6-month study 5 groups of 6 male and 6 female cynomolgus monkeys received NaCl-solution (0.9%), the vehicle, and 50, 200 or 800/400 mg/kg/d (the highest dosage had to be lowered after the first week due to acute drug intolerance) . For clarification of the dose relationship to the findings in the 800/400 mg/kg group, a supplementary 6-month study with 500 mg/kg cefpirome including a vehicle control was also performed . 50 mg cefpirome/kg/d was well tolerated; so too were 160 and 200 mg/kg apart from a slight beta 2-microglobulinuria and/or enzymuria . Almost exclusively at the high dosages retching and vomiting, and exclusively at the high dosages diarrhea, inappetence and physical weakness were sporadically seen in the first phase of the studies . 500 and 400 mg/kg led to increasing signs of discrete renal tubular changes (enzymuria, beta 2-microglobulinuria, cylindruria and minimal histological changes in 2 animals of the 400 mg/kg group) . In one rhesus monkey (500 mg/kg) and two cynomolgus monkeys (800 mg/kg) severe kidney damage had developed within the first week . In all dosage groups of the 90-day study special histological methods revealed a dose-dependent increase and enlargement of lysosomes in the epithelia of the proximal renal tubules . Increased cytolysis was, however, not observed . In all the studies there was a dose-dependent increase in the kidney weights of the intermediate and highest dosage groups . The females of the 400 mg/kg group showed slight anemia accompanied by a slight increase in the reticulocyte count . One animal of this group died prematurely probably due to pulmonary embolism . The signs of slight renal impairment including lysosome enlargement, and the slight anemia proved to be reversible. Pharmacol Biochem Behav, 1990 Nov, 37(3), 417 - 24 Inhibition by antibiotic tetracyclines of rat cortical noradrenergic adenylate cyclase and amphetamine-induced hyperactivity; Kofman O et al.; Two antibiotic tetracyclines, demeclocycline (DMC) and minocycline, share several biochemical and behavioral properties with lithium (Li) . DMC inhibited both noradrenaline- and chloradenosine-sensitive cyclic AMP accumulation in rat cerebral cortical slices both in vitro and ex vivo following two weeks of chronic dietary treatment . Minocycline, a lipophilic tetracycline, produced similar results in vitro . Both DMC and minocycline reduced open-field activity levels in rats following acute treatment, four hours prior to testing . Moreover, both drugs inhibited amphetamine-induced hyperactivity in the open field . Chronic treatment with 0.4% and 0.8% dietary DMC for two weeks attenuated amphetamine hyperactivity without affecting baseline activity levels in the open field . Neither DMC nor minocycline attenuated apomorphine-induced stereotypy at doses that attenuated amphetamine hyperactivity, a profile which is similar to that of lithium . Unlike lithium, however, DMC did not reverse reserpine-induced hypoactivity. Biochemistry, 1990 Oct 23, 29(42), 9795 - 8 Visible light induced DNA cleavage by the hybrid antitumor antibiotic dynemicin A; Shiraki T et al.; Dynemicin A, which is a hybrid antitumor antibiotic containing anthraquinone and enediyne cores, effectively breaks DNA strands upon irradiation with visible light of long wavelength . The preferential cutting sites of visible light induced DNA cleavage with dynemicin A are on the 3'-side of purine bases such as in 5'-AT and 5'-GT sequences . The observed nucleotide cutting specificity is remarkably similar to that of NADPH- (or thiol) induced DNA breakage with dynemicin A, suggesting the presence of the same DNA-cleaving intermediate . Indeed, the photoproduct of dynemicin A is chromatographically identical with the reaction product (dynemicin H) of the thiol-activated dynemicin A . On the basis of the present results, a reasonable mechanism for the visible light induced DNA cleavage of dynemicin A has been proposed. FEBS Lett, 1990 Oct 15, 272(1-2), 171 - 4 Hoogsteen versus Watson-Crick A-T basepairing in DNA complexes of a new group of 'quinomycin-like' antibiotics; Searle MS et al.; The interaction of a new group of 'quinomycin-like' antibiotics with the DNA duplexes d(ACGT)2 and d(GACGTC)2 has been investigated in solution by 1H NMR spectroscopy . By monitoring the intensity of intranucleotide base H6/H8 to deoxyribose H1'NOE cross-peaks we conclude that the terminal A-T basepairs flanking the CG bisintercalation site in the d(ACGT)2 complex adopt the Hoogsteen bonding scheme, with the purine base in a syn conformation . By comparison in the d(GACGTC)2 complex all glycosidic bond angles are anti, consistent with a preferred Watson-Crick basepairing scheme . Both DNA duplexes appear to be significantly unwound compared with the ligand-free DNAs . The data illustrate the influence of helical constraints on the stability of the Hoogsteen bonding scheme adjacent to the drug binding sites. Biochim Biophys Acta, 1990 Oct 5, 1028(2), 174 - 82 Influence of amino acid side-chain modification on the uptake system for beta-lactam antibiotics and dipeptides from rabbit small intestine; Kramer W et al.; The influence of chemical modification of functional amino acid side-chains in proteins on the H(+)-dependent uptake system for orally active alpha-amino-beta-lactam antibiotics and small peptides was investigated in brush-border membrane vesicles from rabbit small intestine . Neither a modification of cysteine residues by HgCl2, NEM, DTNB or PHMB and of vicinal thiol groups by PAO nor a modification of disulfide bonds by DTT showed any inhibition on the uptake of cephalexin, a substrate of the intestinal peptide transporter . In contrast, the Na(+)-dependent uptake systems for D-glucose and L-alanine were greatly inhibited by the thiol-modifying agents . With reagents for hydroxyl groups, carboxyl groups or arginine the transport activity for beta-lactam antibiotics also remained unchanged, whereas the uptake of D-glucose and L-alanine was inhibited by the carboxyl specific reagent DCCD . A modification of tyrosine residues with N-acetylimidazole inhibited the peptide transport system and did not affect the uptake systems for D-glucose and L-alanine . The involvement of histidine residues in the transport of orally active alpha-amino-beta-lactam antibiotics and small peptides (Kramer, W . et al . (1988) Biochim . Biophys . Acta 943, 288-296) was further substantiated by photoaffinity labeling studies using a new photoreactive derivative of the orally active cephalosporin cephalexin, 3-{phenyl-4-3H}azidocephalexin, which still carries the alpha-amino group being essential for oral activity . 3-Azidocephalexin competitively inhibited the uptake of cephalexin into brush-border membrane vesicles . The photoaffinity labeling of the 127 kDa binding protein for beta-lactam antibiotics with this photoprobe was decreased by the presence of cephalexin, benzylpenicillin or dipeptides . A modification of histidine residues in brush-border membrane vesicles with DEP led to a decreased labeling of the putative peptide transporter of Mr 127,000 compared to controls . This indicates a decrease in the affinity of the peptide transporter for alpha-amino-beta-lactam antibiotics by modification of histidine residues . The data presented demonstrate an involvement of tyrosine and histidine residues in the transport of orally active alpha-amino-beta-lactam antibiotics across the enterocyte brush-border membrane. Appl Environ Microbiol, 1990 Oct, 56(10), 3179 - 85 Thiophene-degrading Escherichia coli mutants possess sulfone oxidase activity and show altered resistance to sulfur-containing antibiotics; Juhl MJ et al.; We have previously isolated mutants of Escherichia coli which show increased oxidation of heterocyclic furan and thiophene substrates . We have now found that strains carrying the thdA mutation express a novel enzyme activity which oxidizes a variety of substrates containing a sulfone (SO2) moiety . Both heterocyclic sulfones (e.g., tetramethylene sulfone) and simple aliphatic sulfones (e.g., ethyl sulfone) were oxidized . The thdA mutants were more resistant than wild-type strains to aromatic sulfone antibiotics such as dapsone . In contrast they showed increased susceptibility to thiolutin, a cyclic antibiotic containing sulfur at the sulfide level of oxidation . Several new thdA mutant alleles were isolated by selecting for increased oxidation of various aliphatic sulfur compounds . These new thdA mutants showed similar sulfone oxidase activity and the same map location (at 10.7 min) as the original thdA1 mutation . The constitutive fadR mutation was required for the phenotypic expression of thdA-mediated oxidation of sulfur compounds . However, the thdA-directed expression of sulfone oxidase activity was not fadR dependent . The thdC and thdD mutations probably protect against the toxicity of thiophene derivatives rather than conferring improved metabolic capability. J Antimicrob Chemother, 1990 Oct, 26 Suppl B, 129 - 39 Comparison of the activity of three antibiotic regimens in severe Legionnaires' disease; Dournon E et al.; Comparison of the activity of different antibiotic regimens in Legionnaire's disease has never been made because of the rarity of well documented cases of that disease . We have retrospectively compared severe cases of Legionnaires' disease treated with pefloxacin alone or in combination with erythromycin and/or rifampicin using computer-matched cases treated either with erythromycin or with erythromycin in combination with rifampicin . This study suggests that: (1) combined therapy including erythromycin, rifampicin and/or pefloxacin is superior to therapy with erythromycin alone; (2) combinations including pefloxacin may be the most active ones; and (3) pefloxacin alone may be as active as combination therapy . Although these results are in agreement with data obtained in cell and in animal models of legionella infection they need to be further confirmed by the study of larger number of patients. J Antibiot (Tokyo), 1990 Oct, 43(10), 1223 - 9 New antifungal antibiotics pradimicins FA-1 and FA-2: D-serine analogs of pradimicins A and C; Sawada Y et al.; Pradimicin FA-1 was produced via directed biosynthesis with substitution of D-serine for D-alanine in the 15-position of pradimicin A . This substitution was achieved by the addition of D-serine to the culture medium of Actinomadura hibisca P157-2 . Likewise, pradimicin FA-2 was co-produced along with pradimicin FA-1 when the pradimicins A and C producing strain, A . hibisca A2493 was grown in D-serine-supplemented medium . The new pradimicin analogs share a common core structure of 5,6-dihydrobenzo{a}naphthacenequinone substituted by D-serine at C-15, but differ in the disaccharide moiety at C-5 . Pradimicin FA-1 has an N-methylamino sugar and D-xylose . Pradimicin FA-2 is the des-N-methyl analog of pradimicin FA-1 . The in vitro and in vivo antifungal activity of the analogs was comparable to that of pradimicin A. Br J Hosp Med, 1990 Oct, 44(4), 252 - 8, 261-3 Mechanisms and clinical significance of resistance to new beta-lactam antibiotics; Livermore DM et al.; The newer beta-lactam antibiotics, including various ureidopenicillins, second- and third-generation cephalosporins, carbapenems and monobactams, are active against many bacteria that are resistant to older penicillins, such as ampicillin and ticarcillin . Nonetheless, resistance to the newer agents can arise, and in this article the mechanisms whereby it does so are reviewed and their clinical significance is discussed. Neurology, 1990 Oct, 40(10), 1535 - 40 Borrelia burgdorferi infection of the brain: characterization of the organism and response to antibiotics and immune sera in the mouse model; Pachner AR et al.; To learn more about the neurologic involvement in Lyme disease, we inoculated inbred mice with the causative agent of Lyme disease, Borrelia burgdorferi . We cultured brains and other organs, and measured anti-B burgdorferi antibody titers . We further studied a brain isolate for its plasmid DNA content and its response in vitro to immune sera and antibiotics . One strain of B burgdorferi, N40, was consistently infective for mice, and resulted in chronic infection of the bladder and spleen . SJL mice developed fewer culture-positive organs and had lower antibody titers than Balb/c and C57Bl/6 mice . Organism was cultured from the brain early in the course of infection, and this isolate, named N40Br, was further studied in vitro . The plasmid content of N40Br was different from that of the infecting strain, implying either a highly selective process during infection or DNA rearrangement in the organism in vivo . N40Br was very sensitive to antibiotics, but only after prolonged incubation . Immune sera from both mice and humans infected with B burgdorferi were unable to completely kill the organism by complement-mediated cytotoxicity . These data demonstrate that B burgdorferi infects the brain of experimental animals, and is resistant to immune sera in vitro but sensitive to prolonged treatment with antibiotics. J Antibiot (Tokyo), 1990 Oct, 43(10), 1307 - 15 Footprinting studies of the interaction of quinomycin antibiotic UK63052 with DNA: comparison with echinomycin; Fox KR; The interaction between UK63052, a novel derivative of the quinomycin group of bifunctional intercalating antibiotics, with DNA has been investigated by footprinting techniques and the results compared with echinomycin . UK63052 binds strongly but reversibly to DNA and decreases the gel mobility of most DNA fragments, although the mobility of bent kinetoplast DNA is increased . The drug binds selectively to the dinucleotide CpG though not all such sequences present good binding sites . Binding is best when CG is surrounded by AT base pairs . UK63052 and echinomycin have different effects on DNA structure as assessed by changes in the sensitivity to modification by diethylpyrocarbonate . The results are interpreted by suggesting that substitutions on the chromophores affect the precise details of DNA recognition. Poult Sci, 1990 Oct, 69(10), 1787 - 91 Effects of different antibiotics on performance, processing characteristics, and parts yield of broiler chickens; Izat AL et al.; Broilers were grown to 49 days of age on diets supplemented with bambermycins (BAM, 2.2 ppm), bacitracin methylene disalicylate (BMD, 27.5 ppm), virginiamycin (VM, 11 ppm), or an unmedicated control . Samples of birds were processed for dressing percentage and parts yield . There were no significant (P greater than .05) effects of antibiotics on final body weight, feed conversion, or mortality . In male broilers, BMD and VM significantly (P less than or equal to .05) increased dressing percentage and percentage yield and reduced the skeletal rack as a percentage of postchill weight compared to those fed the nonmedicated control . All antibiotics significantly increased breast skin weight and breast skin as a percentage of postchill weight of as compared with those fed the unmedicated control . In female broilers, BAM and BMD significantly increased dressing percentage and percentage yield and increased breast weight and breast as percentage of postchill weight as compared with those fed the unmedicated control diet . Females fed BMD also had significantly heavier leg quarters and breast skin than those fed the unmediated control . Females fed VM had increased breast skin weight and breast skin as a percentage of postchill weight than those fed the unmedicated control . The results of the present study indicate that antibiotics may influence dressing percentage and parts yield in the absence of improvements in body weight gain or feed utilization. Boll Chim Farm, 1990 Oct-Nov, 129(10-11), 49S - 52S {Therapeutic efficacy and general tolerability of 4-carbomethoxythiazolidine chlorohydrate in combination with antibiotic and bronchoactive therapy in adult patients with acute and chronic bronchopneumopathy with prevalent exudative component}; Casali L; 20 patients, aged between 31 and 71, have been treated . All were hospitalized because of acute or chronic broncho-pneumopathy and have been administered 4-carbomethoxythiazolidine at a dosage of 300 mg/d . in association with the common antibiotic or chemiotherapic treatments . Every day all symptoms have been registered (asthenia, cephalea, sibiluses, rhoncuses, rales, inspiratory and expiratory dyspnea) . Before and after the treatment some respiratory functioning tests have been performed, including the VEMS and VEMS/CV determination . A further study on the distribution of the inhaled air has been carried out, as well as on the ventilation/perfusion ratio by means of He and CO2 curves . At the beginning and at the end of the TMC treatment some hematiobiologic tests have been carried out, including: haemochromo with leukocytic formula, blood platelets counting, VES, glycemia, azotemia, transaminase, alkaline phosphatase, total bilirubinaemia, prothrombinic activity and determination of urine's specific weight . The pulmonary symptomatology (cough, sibiluses, rhoncuses, rates, inspiratory and expiratory dyspnea), was markedly reduced . Even if, as for the preliminary character of the experiment, we can state that 4-carbomethoxythiazolidine is a drug with an outstanding level of tolerance. Postgrad Med J, 1990 Oct, 66(780), 858 - 9 Anaphylactic reactions to topical antibiotic combinations; Eedy DJ et al.; We describe two patients who developed anaphylaxis type reactions following the application of the topical antibiotic Polyfax (polymixin B and bacitracin) . We draw attention to this potentially serious complication of topical antibiotic preparations and emphasize the need for careful history taking before prescribing such preparations. Mol Microbiol, 1990 Oct, 4(10), 1679 - 91 Spore colour in Streptomyces coelicolor A3(2) involves the developmentally regulated synthesis of a compound biosynthetically related to polyketide antibiotics; Davis NK et al.; Streptomyces coelicolor produces spores whose development of a grey colour requires the activity of the whiE locus . The cloned whiE locus was identified after mobilization into a whiE mutant of a library of S . coelicolor DNA inserted into a transmissible plasmid vector . The whiE region of the cloned DNA was localized both by subcloning and by mutagenesis of the cloned DNA with the Streptomyces transposon Tn4560 . Nucleotide sequencing of this region revealed seven open reading frames, of which six show homology at the level of deduced gene products with genes involved in the synthesis of polyketide antibiotics . A previously described S . coelicolor DNA segment encoding biosynthesis of a brown pigment (Horinouchi and Beppu, 1985) corresponds to the cloned whiE DNA . It is proposed that whiE is normally expressed only in the aerial hyphae, where the biosynthetic product is responsible for spore colour. Planta Med, 1990 Oct, 56(5), 446 - 50 Strobilurin D and strobilurin F: two new cytostatic and antifungal (E)-beta-methoxyacrylate antibiotics from Cyphellopsis anomala (1); Weber W et al.; Strobilurin D and strobilurin F, two new cytostatic and antifungal antibiotics of the (E)-beta-methoxyacrylate class, have been isolated from mycelial cultures of the basidiomycete Cyphellopsis anomala (Pers . ex Fr.) Sing . The structures were elucidated by spectroscopic methods . The antibiotics inhibit the growth of human and animal cells and a wide variety of fungi . Like strobilurins A and B, the new metabolites are potent inhibitors of respiration. FEBS Lett, 1990 Sep 17, 270(1-2), 139 - 42 Revised structure of the peptide lactone antibiotic, TL-119 and/or A-3302-B; Kitajima Y et al.; The peptide lactone antibiotic TL-119 and/or A-3302-B was chemically synthesized in order to confirm the proposed structure . The synthetic compound was different from both natural TL-119 and A-3302-B in their physicochemical properties and in biological activity . Re-examination of the configuration of the constituent amino acid residues in natural TL-119 and/or A-3302-B indicated that natural TL-119 and A-3302-B contains D-aThr instead of the original L-Thr . We tentatively propose a revised structure for TL-119 and/or A-3302-B. Cancer Res, 1990 Sep 15, 50(18), 5841 - 4 Induction of mammalian DNA topoisomerase II dependent DNA cleavage by antitumor antibiotic streptonigrin; Yamashita Y et al.; Streptonigrin, a nonintercalative antitumor antibiotic, induced mammalian topoisomerase II dependent DNA cleavage in vitro . The cleavage activity of streptonigrin was comparable to that of demethylepipodophyllotoxin ethylidene-beta-D-glucoside at a low concentration (less than or equal to 10 microM) but one-third lower at a higher concentration (greater than 250 microM) . Exposure of a reaction mixture containing streptonigrin, DNA, and topoisomerase II to an elevated temperature (65 degrees C) resulted in substantial reduction in DNA cleavage, suggesting that the mechanism of the topoisomerase II dependent DNA cleavage induced by streptonigrin was through the formation of a cleavage complex previously reported for topoisomerase II poisons such as 4'-(9-acridinylamino) methanesulfon-m-anisidide and epipodophyllotoxins. Cancer Res, 1990 Sep 1, 50(17), 5475 - 80 Prevention of central nervous system toxicity of the antitumor antibiotic acivicin by concomitant infusion of an amino acid mixture; Williams MG et al.; Acivicin is an investigational amino acid antitumor antibiotic currently being evaluated in Phase II clinical trials . In humans acivicin causes reversible, dose-limiting central nervous system (CNS) effects including somnolence, ataxia, personality changes, and hallucinations . We have observed and reported previously that acivicin-treated cats exhibit symptoms (ataxia, sedation, somnolence) resembling CNS toxicity reported in humans . We hypothesized that if acivicin uptake into brain were mediated by a saturable transport system common to endogenous amino acids, drug uptake and CNS toxicity might be blocked by elevation of normal amino acid concentrations in circulating plasma . To test this hypothesis, cats received constant-rate i.v . infusions of either saline or Aminosyn, 10% (a commercially available mixture of 16 amino acids not containing glutamine, glutamate, aspartate, or cysteine) for 4 h prior to and 18 h subsequent to administration of acivicin at a dose producing marked behavioral changes in control cats . Presence or absence of ataxia and sedation were noted at intervals after acivicin treatment . Results showed that Aminosyn infusion prevented CNS symptoms in six of eight cats . Subsequent experiments showed that acivicin levels in brain tissue of Aminosyn-treated cats were 13% of the drug levels in saline-infused cats . Acivicin levels in most peripheral tissues were also decreased significantly by Aminosyn infusion but not to the extent observed in brain . Decreased brain uptake was shown to be due to a combination of amino acid blockade of drug transport into that organ and of increased total body clearance of drug . Concomitant Aminosyn treatment did not alter the efficacy of acivicin in mice bearing L1210 leukemia or MX-1 human mammary carcinoma . Further studies demonstrated that a solution containing only four large neutral amino acids (leucine, isoleucine, phenylalanine, and valine) could also protect cats from acivicin-induced CNS toxicity, apparently without increasing acivicin total body clearance . However, a mixture of several other amino acids contained in Aminosyn (alanine, arginine, tyrosine, histidine, proline, serine, and glycine) failed to prevent CNS toxicity . We conclude that cotreatment with Aminosyn or a mixture of large neutral amino acids could protect cancer patients from acivicin-induced CNS toxicity without ablating antitumor efficacy. Contraception, 1990 Sep, 42(3), 297 - 308 The need for prophylactic antibiotics after female sterilization: tetracycline in Bangladesh; Akhter HH et al.; All female sterilization patients in Bangladesh receive five-day courses of tetracycline capsules every six hours as a postoperative prophylactic . A double-blind randomized study was conducted by the Bangladesh Fertility Research Programme (BFRP) to determine whether prophylactic antibiotics reduced infection after minilaparotomy, and to compare the prophylactic effectiveness of tetracycline and ampicillin . Women recruited from throughout Bangladesh (N = 1350) received five-day courses of 250 mg tetracycline, 250 mg ampicillin, or placebo . The infection rate was significantly lower with tetracycline than with placebo (6% vs 10% with placebo), but did not differ significantly between the ampicillin and placebo groups or between the tetracycline and ampicillin groups. Chem Pharm Bull (Tokyo), 1990 Sep, 38(9), 2518 - 22 Estimation of the molecular volumes of the reaction products between beta-lactam antibiotics and aminoglycoside antibiotics, and those of the degradation products of beta-lactam antibiotics by isotachophoresis; Fujishita O et al.; The correlative equations between the molecular volume and the qualitative indication (hR) for beta-lactam antibiotics, the reaction products between beta-lactam antibiotics and kanamycin, and the degradation products of beta-lactam antibiotics were hR = 0.32 + 0.080 VA2/3//Z/(N = 15, r = 0.972 for penicillins) and hR = 0.04 + 0.072 VA2/3//Z/(N = 12, r = 0.987 for cephems) . Where VA is van der Waals volume (A3/molecule), hR is the relative step height in the isotachopherogram, and Z is the electric change, respectively . According to these equations, the molecular volumes of the reaction products between beta-lactam antibiotics and the other aminoglycoside antibiotics, and those of the degradation products of beta-lactam antibiotics can be estimated from the value of hR . Also according to the step height in the isotachopherogram, the reaction products or the degradation products may be estimated directly when the electric charge is known . It was confirmed that a molecule of aminoglycoside antibiotics reacted with a molecule of beta-lactam antibiotics . Therefore, the inactivation of aminoglycoside antibiotics is much greater than for beta-lactam antibiotics when the clinical doses of these antibiotic combinations are used. J Assoc Off Anal Chem, 1990 Sep-Oct, 73(5), 813 - 7 Validation of a method for determination of tetracycline antibiotics in salmon muscle tissue; Reimer GJ et al.; A method was validated for analysis of oxytetracycline (OTC), tetracycline (TC), and chlortetracycline (CTC) in fortified salmon muscle tissue . Recoveries of OTC were 100 +/- 6, 86 +/- 6, and 82 +/- 5% (n = 6) at fortification levels of 1.0, 0.5, and 0.2 ppm, respectively . Recoveries of TC were 68 +/- 4, 65 +/- 6, and 66 +/- 7%; recoveries of CTC were 45 +/- 9, 48 +/- 8, and 0%, respectively . Detection limits for OTC and TC were 0.08 and 0.09 ppm, respectively. J Hand Surg {Am}, 1990 Sep, 15(5), 761 - 4 Role of antibiotics in open fractures of the finger; Suprock MD et al.; The role of antibiotics was investigated prospectively in 91 open fractures of the finger . Antibiotics were administered to alternate patients with open phalangeal fractures . Only finger fractures distal to the metacarpophalangeal joint were included . Both groups were treated with aggressive surgical irrigation and debridement . In four patients in each group clinical signs of infection eventually developed; osteomyelitis did not develop in any patients, and no secondary surgical procedures were required in either group . This data indicates that vigorous irrigation and debridement is adequate primary treatment for open phalangeal fractures in fingers with intact digital arteries. Gene, 1990 Sep 1, 93(1), 91 - 9 Cloning and expression in a heterologous host of the complete set of genes for biosynthesis of the Streptomyces coelicolor antibiotic undecylprodigiosin; Malpartida F et al.; A fragment of DNA carrying the hitherto unisolated members of the cluster of genes (red) for biosynthesis of the red-pigmented antibiotic undecylprodigiosin of Streptomyces coelicolor A3(2) was isolated . This was done by cloning random fragments of S . coelicolor DNA into the closely related Streptomyces lividans 66 and recovering a clone that caused overproduction of undecylprodigiosin . The effect was probably due to the presence of the cloned redD gene, which functions as a positive regulator of the expression of the red cluster, activating the normally poorly expressed red genes of S . lividans . Two fragments from either end of the red cluster were cloned adjacent to each other on a low-copy-number Streptomyces vector . Double crossing-over occurring between these plasmid-borne sequences and the chromosomal copy of the same DNA in S . coelicolor led to isolation of the entire red cluster as a single cloned fragment . Isolation of antibiotic biosynthetic genes by the effects of an activator in a self-cloning experiment, and in vivo reconstitution of a large cluster of genes by homologous recombination, may turn out to be usefully generalizable procedures. J Perinatol, 1990 Sep, 10(3), 252 - 6 Prolongation of the latency period in preterm premature rupture of the membranes using prophylactic antibiotics and tocolysis; Fortunato SJ et al.; Mixed results have been obtained in several studies using tocolysis or antibiotics individually in the treatment of premature rupture of membranes (PROM) . We compared the outcomes of a management protocol consisting of tocolysis, prophylactic antibiotic administration, and documentation of pulmonary maturity with a control group treated with passive expectant management for premature rupture of membranes . There were 55 women in the treatment group and 57 women in the control group . The mean latent phase (+/- SEM) in the treatment group was 7.34 (+/- 1.25) days compared with 1.86 (+/- .431) days in the control group (P less than .001) . Eighteen of 55 patients (33%) in the treatment group were electively delivered after documentation of lung maturity, contributing to a falsely lowered mean latent phase in the treatment group . Twenty-four patients in the treatment group and 6 in the control group had a latent phase of 5 days or greater (P = .00018) . There were 9 postpartum infections in the control group and 10 infections in the treatment group (P = NS) . There was no difference in the length of latent phase of patients treated with ceftizoxime compared with the other antibiotics used (cefoxitin, cefazolin, ampicillin), although postpartum ceftizoxime was more effective in preventing postpartum infections (1 of 28 vs 9 of 27) (P = .005) . There were fewer infected neonates in the study group, but this was not significant . It appears that treatment with this protocol significantly prolongs the latent phase in patients with preterm PROM without increasing infectious morbidity. Am J Obstet Gynecol, 1990 Sep, 163(3), 743 - 7 Antibiotic therapy in preterm premature rupture of membranes: a randomized, prospective, double-blind trial; Johnston MM et al.; The use of antibiotics in the management of preterm, premature rupture of membranes remains controversial . By use of a prospective randomized double-blind design we investigated the maternal-fetal benefits associated with antibiotic therapy in 85 women with premature rupture of membranes at 34 weeks' estimated gestational age . In the treatment group 40 patients received intravenous mezlocillin for 48 hours followed by oral ampicillin until delivery . In the control group 45 patients received intravenous and oral placebo . Patients who received antibiotics had chorioamnionitis and endometritis less frequently than the control group (p less than 0.01 and p less than 0.05) . Pathologic examination of the placentas showed a lower incidence of chorioamnionitis in the treatment group (p less than 0.05) . The period from premature rupture of membranes to delivery (latency) was prolonged with antibiotics (p less than 0.05) and resulted in significant weight gain in the infants in the antibiotic group (p less than 0.0001) . These infants also had higher 1- and 5-minute Apgar scores . Clinically suspected sepsis, respiratory distress syndrome, intraventricular hemorrhage, perinatal death rate, and prolonged hospitalization (greater than 30 days) were also increased in the control group. Proc Natl Acad Sci U S A, 1990 Sep, 87(17), 6609 - 13 Inter- and intraspecies spread of Escherichia coli in a farm environment in the absence of antibiotic usage; Marshall B et al.; The spread of wild-type Escherichia coli bearing a transferable plasmid was studied in a farm environment . E . coli of bovine and porcine origin were marked by resistance to nalidixic acid (Nar) or rifampicin (Rfr), and a transferable, multiple resistance plasmid (pSL222-1 derivative of plasmid R222) was introduced by conjugation . In separate experiments, the two mutant derivatives were fed back to the respective host animals, which were housed adjacent to, but separate from, one or more "recipient" animals . No antibiotic was given . Although the Rfr derivatives declined rapidly to undetectable levels within 1 week, the Nar mutants of bovine and porcine origin persisted in the original hosts and in their bedding throughout most of each 4-month test period . Test bacteria were isolated from mice residing in the same pen as the donor animals and from multiple secondary hosts having direct or indirect contact with the inoculated donors, but not from neighboring animals maintained in isolation . The bovine mutant was excreted by two caretakers for greater than 4 weeks and was recovered for 4-6 weeks from pigs, fowl, and flies . Although the porcine mutant appeared to colonize less effectively, it spread rapidly to flies and mice and was recovered transiently from humans and fowl . Despite high transfer rates of plasmid pSL222-1 from E . coli K-12 in vitro, transfer of the plasmid from the animal E . coli host was very low and transfer in vivo was not detected among indigenous gut or environmental bacteria . E . coli of animal origin can spread rapidly and can colonize the intestinal tract of humans and of other animals in the absence of antibiotic selection. J Urol, 1990 Sep, 144(3), 780 - 4 Bacterial epididymitis in the rat: a model for assessing the impact of acute inflammation on epididymal antibiotic penetration; See WA et al.; A rat model of bacterial epididymitis was developed and characterized for use in assessing the impact of acute epididymal inflammation on antibiotic penetration into the epididymis . A 0.2 ml . intratesticular injection of a 0.5 McFarland standard suspension of E . coli resulted in histologically confirmed acute epididymitis in all animals studied . Inflammatory changes were detectable as early as 24 hours following inoculation and were progressive to the last assessment point at 11 days . Early testicular infarction was observed in association with epididymal inflammation . Serial transcrotal ultrasounds of infected animals showed progressive increase in epididymal size and a late decrease in testicular size . Serum and epididymal drug concentrations were assayed following a single dose of the antibiotic amdinocillin . Fifteen minutes following the peak serum level, the drug concentration in infected epididymis was 2.3-fold higher than the contralateral, non-infected epididymis . These data suggest that acute inflammation enhances antibiotic penetration into the infected epididymis . The model described provides a rapid, reproducible method to study epididymal drug delivery in normal and diseased states. Zh Mikrobiol Epidemiol Immunobiol, 1990 Sep, (9), 10 - 5 {Activation of the alarm response of Escherichia by antibiotics}; Tets VV et al.; The data on the effect of antibiotics suppressing the synthesis of protein on the activation of the SOS-system are presented . The action of tetracycline, chloramphenicol rifampicin and nalidixic acid, a well-known activator of SOS-response, has been studied . The short-term action of inhibitory concentrations and the prolonged action of subinhibitory concentrations of these preparations on the activity of genes rec A and sul A and the induction of the synthesis of phage lambda have been considered . Chloramphenicol and tetracycline, as well as nalidixic acid, have been shown to be capable of activating genes rec A, sul A and synthesis of the phage . The induction of SOS-response has been found to be more pronounced in the short-term action of inhibitory concentrations of antibiotics on bacteria than in the prolonged subinhibitory concentrations. Ann Ostet Ginecol Med Perinat, 1990 Sep-Oct, 111(5), 296 - 320 {Infections in obstetric-gynecologic surgery: chemo-antibiotic prophylaxis and therapy . A bibliographic review}; Franchi M et al.; The Authors review, on the basis of their experience, the literature data concerning chemo-antibiotic prophylaxis in gynaecological surgery . Prophylaxis is widely employed although some important aspects are still under evaluation: bacterial selection and resistance, benefit in case of abdominal hysterectomy or elective Cesarean section, risk of pseudomembranous colitis . The most effective drugs are Piperacillin/Mezlocillin given in a single dose preoperatively . The same drugs are useful in the treatment of postsurgical infections. Arzneimittelforschung, 1990 Sep, 40(9), 1034 - 8 Subchronic and chronic toxicity of the new antibiotic cefpirome in rats; Donaubauer HH et al.; Subchronic and chronic toxicity studies in rats were performed with 3-{(2,3-Cyclopenteno-1-pyridinium)-methyl}- 7-{2-syn-methoximino-2-(2-aminothiazol-4-yl)-acetamido} -ceph-3-em-4- carboxylate (cefpirome, HR 810), a new cephalosporin derivative . In subchronic (14 day) studies cefpirome was intravenously administered in dose levels up to 1500 mg/kg/d with good kidney tolerance . Signs of renal functional impairment were observed (800 and 1500 mg/kg) but histologically no morphological changes could be detected . The chronic intraperitoneal administration (90 day) of cefpirome at dose levels of 400 or 1600 mg/kg/d resulted in some reversible changes in hematology (slight anemia), serum-chemistry parameters (liver), urinalysis (proteinuria), and histopathology (increased numbers and enlargement of lysosomes in proximal tubular epithelia of the kidneys and pigment deposits in follicle epithelia of the thyroids), predominantly in high-dose animals . The "no effect level" is considered to be 100 mg/kg/d in this study. Antiviral Res, 1990 Sep, 14(3), 173 - 8 Inhibitory effect of a new antibiotic, guanine 7-N-oxide, on the replication of several RNA viruses; Yamamoto K et al.; Guanine 7-N-oxide (G-7-Ox) was examined for its antiviral activity against 9 viruses based on plaque reduction, neuraminidase activity reduction, a fluorescent antibody technique or ELISA . The following viruses were included in the tests: influenza, Sendai, simian virus 5 (SV5), respiratory syncytial, western equine encephalitis, Japanese encephalitis, vesicular stomatitis, rabies and polio . G-7-Ox showed broad anti-RNA viral activity against all viruses tested, except for poliovirus . Inhibition of persistent SV5 infection by G-7-Ox indicates that its antiviral activity is independent of cytotoxicity. Vopr Med Khim, 1990 Sep-Oct, 36(5), 39 - 41 {The effect of the polyether antibiotic omomycin on the activity of cyclic nucleotides in the primary culture of newborn rat heart cells}; Gerasimova TsI et al.; Content of cyclic nucleotides was studied in primary culture of newborn rat heart cells after administration of the polyether-containing antibiotic omomycin (985-I, 16-diethyl indanomycin) . Level of cGMP was increased within 10 min of the cells exposition with 4 micrograms/ml of the antibiotic, while the nucleotide content elevation was more significant in presence of 1-methyl-3-isobutyl xanthine (10(-4) M) . When the exposition time was prolonged up to 20 min, content of cGMP returned to control values in absence of isobutyl xanthine and remained at the elevated level in presence of the drug . Content of cAMP was unaltered under these conditions . Omomycin may be used in experiments, where distinct increase of the cellular cGMP content is required. Eur J Biochem, 1990 Aug 28, 192(1), 1 - 15 Nonribosomal biosynthesis of peptide antibiotics; Kleinkauf H et al.; Peptide antibiotics are known to contain non-protein amino acids, D-amino acids, hydroxy acids, and other unusual constituents . In addition they may be modified by N-methylation and cyclization reactions . Their biosynthetic origin has been connected in many cases to an enzymatic system referred to as the 'thiotemplate multienzymic mechanism' . This mechanism includes the activation of the constituent residues as adenylates on the enzymic template, the acylation of specific template thiol groups, epimerization or N-methylation at this thioester stage, and polymerization in the sequence directed by the multienzymic structure with the aid of 4'-phosphopantetheine as a cofactor, including possible cyclization or terminal modification reactions . The reaction sequences leading to gramicidin S, tyrocidine, cyclosporine, bacitracin, polymyxin, actinomycin, enniatin, beauvericin, delta-(L-alpha-aminoadipyl)-L-cysteinyl-D-valine and linear gramicidin are discussed . The structures of the multienzymes, their genetic organization, the biological functions of these peptides and results on related systems are discussed. Biochim Biophys Acta, 1990 Aug 17, 1035(2), 218 - 22 Basement membrane collagen-degrading activity from a malignant tumor is inhibited by anthracycline antibiotics; Karakiulakis G et al.; Type IV collagenase activity was previously identified and purified to 7500-fold in homogenates from murine Walker 256 carcinoma, using acetylated {3H}-type IV collagen as a substrate . Anthracycline antibiotics daunorubicin, doxorubicin and epirubicin exhibited a non-competitive, reversible inhibition with Ki 92, 49 and 40 microM, respectively . This inhibitory effect, at therapeutically attainable concentrations of the forementioned antineoplastic drugs, may contribute, at least in part, to their antimetastatic properties . The anthracycline derivatives: 4-demethoxydaunorubicin, 4'-iododoxorubicin and 4-demethoxy-3'-deamino-3'-hydroxyepirubicin were without inhibitory effects at comparable concentrations . Other antineoplastic agents, such as belomycin, carmustine, cisplatine, etoposide, methotrexate, mitotane and teniposide did not exhibit any inhibitory effect at concentrations up to 1.0 mM. Biochim Biophys Acta, 1990 Aug 10, 1027(1), 25 - 30 Interaction of renin inhibitors with the intestinal uptake system for oligopeptides and beta-lactam antibiotics; Kramer W et al.; The interaction of two renin inhibitors, S 86,2033 and S 86,3390, with the uptake system for beta-lactam antibiotics and small peptides in the brush border membrane of enterocytes from rabbit small intestine was investigated using brush border membrane vesicles . Both renin inhibitors inhibited the uptake of the orally active cephalosporin cephalexin into brush border membrane vesicles from rabbit small intestine in a concentration-dependent manner . 1.1 mM of S 86,3390 and 2.5 mM of S 86,2033 led to a half-maximal inhibition of the H(+)-dependent uptake of cephalexin . Both renin inhibitors were stable against peptidases of the brush border membrane . The uptake of cephalexin into brush border membrane vesicles (1 min of incubation) was competitively inhibited by S 86,2033 and S 86,3390 suggesting a direct interaction of these compounds with the intestinal peptide uptake system . The renin inhibitors are transported across the brush border membrane into the intravesicular space as was shown by equilibrium uptake studies dependent upon the medium osmolarity . The uptake of S 86,3390 was stimulated by an inwardly directed H(+)-gradient and occurred with a transient accumulation against a concentration gradient (overshoot phenomenon) . The renin inhibitors S 86,2033 and 86,3390 also caused a concentration-dependent inhibition in the extent of photoaffinity labeling of the putative peptide transport protein of apparent Mr 127,000 in the brush border membrane of small intestinal enterocytes . In conclusion, these studies show that renin inhibitors specifically interact with the intestinal uptake system shared by small peptides and beta-lactam antibiotics. Anticancer Drug Des, 1990 Aug, 5(3), 265 - 71 Anti-cancer activity of anthracycline antibiotics and DNA condensation; Cera C et al.; Light scattering techniques were used to investigate the ability of a number of anthracyclines to cause compaction in double-stranded DNA and nucleosomes at physiological ionic strength . The structurally organized polynucleotide was efficiently condensed by all of the drugs examined, while no appreciable aggregation of free double-stranded DNA is observed under the same experimental conditions . A model for the process is proposed . Our results suggest the lack of a direct relationship between the critical concentration of free drug at which condensation of DNA occurs and the cytotoxic and anti-cancer properties exhibited by the various anthracycline derivatives. Biochem Pharmacol, 1990 Aug 1, 40(3), 499 - 506 Effect of acidic phospholipids on the activity of lysosomal phospholipases and on their inhibition induced by aminoglycoside antibiotics--II . Conformational analysis; Mingeot-Leclercq MP et al.; In a companion paper (Mingeot-Leclercq et al . Biochem Pharmacol 40: 489-497, 1990), we showed that the inhibitory potency of gentamicin on the activity of lysosomal phospholipases, measured towards phosphatidylcholine included in negatively-charged liposomes, is markedly influenced by the nature of the acidic phospholipid used (phosphatidylinositol, phosphatidylserine, phosphatidic acid), whereas the binding of the drug to the three types of liposomes is similar . This result challenged previous conclusions pointing to a key role exerted by drug binding to phospholipid membranes and presumably charge neutralization, for phospholipases inhibition (Carlier et al . Antimicrob Agents Chemother, 23: 440-449, 1983; Mingeot-Leclercq et al., Biochem Pharmacol 37:591-599, 1988) . Conformational analysis of mixed monolayers of gentamicin and each of the three acid phospholipids shows that gentamicin systematically adopts an orientation largely parallel to the hydrophobic-hydrophilic interface, but that (i) the energies of interaction are largely different (phosphatidylinositol greater than phosphatidylserine greater than phosphatidic acid), and (ii) the apparent accessibility of the bound drug to water varies in an inverse relation with the energies of interaction . Amikacin, a semisynthetic derivative of kanamycin A with a lower inhibitory potential towards phospholipases than gentamicin in the three types of liposomes used, also showed similar differences in energies of interaction and accessibility to water, but constantly exhibited an orientation perpendicular to the hydrophobic-hydrophilic interface . We conclude that impairment of lysosomal phospholipase activities towards phosphatidylcholine included in negatively-charged membranes by aminoglycoside antibiotics is indeed dependent upon drug binding to the bilayer, but is also modulated by (i) the nature of the acidic phospholipid, which influences the energy of interaction and the accessibility of the drug with respect to the hydrophilic phase, and (ii) the orientation of the drug, which it itself related to its chemical structure . Inasmuch as phospholipases inhibition is related to aminoglycoside nephrotoxicity, these findings may help in better defining the molecular determinants and mechanisms responsible for this adverse effect. Biochem Pharmacol, 1990 Aug 1, 40(3), 489 - 97 Effect of acidic phospholipids on the activity of lysosomal phospholipases and on their inhibition by aminoglycoside antibiotics--I . Biochemical analysis; Mingeot-Leclercq MP et al.; Aminoglycoside antibiotics accumulate in lysosomes of kidney and cultured cells and cause an impairment of phospholipid catabolism which is considered to be an early and significant step in the development of their toxicity . Using liposomes, wer previously demonstrated that the activity of lysosomal phospholipases A1 and A2 towards phosphatidylcholine was markedly enhanced by the inclusion of phosphatidylinositol in the bilayer, and that gentamicin impaired this activity by binding to phosphatidylinositol . Since gentamicin-induced inhibition was inversely related to the amount of phosphatidylinositol included in the liposomes, we proposed that gentamicin impairs activity of phospholipases by decreasing the quantity of available negative charges carried by the bilayer surface (Mingeot-Leclercq et al., Biochem Pharmacol 37: 591-599, 1988) . We now extend these observations to phosphatidylserine and phosphatidic acid, and compare the inhibition caused by gentamicin, amikacin and streptomycin towards lysosomal phospholipases on the hydrolysis of phosphatidylcholine in the presence of each of these acidic phospholipids . Inclusion of phosphatidic acid in liposomes, and, to a lesser extent, phosphatidylserine, caused a larger increase in phospholipases activity than phosphatidylinositol . In parallel, the three aminoglycosides tested were found less inhibitory towards phospholipases activity measured on phosphatidic acid-or phosphatidylserine-containing liposomes than was previously observed with phosphatidylinositol, even though equilibrium dialysis experiments failed to demonstrate significant difference in binding parameters of the drug towards each of these liposomes populations . Yet, as for phosphatidylinositol-containing liposomes, the inhibition was inversely related to the amount of phosphatidic acid or phosphatidylserine included in the bilayer and the inhibitory potency of the three drugs was consistently gentamicin greater than amikacin greater than streptomycin with the three types of negatively-charged liposomes used . We conclude that impairment of lysosomal phospholipases activity towards phosphatidylcholine included in negatively-charged membranes by aminoglycoside antibiotics is dependent upon drug binding to the bilayer, but that it is modulated by the nature of the acidic phospholipid that binds the drug as well as by that of the drug itself . A companion paper (Mingeot-Leclercq et al., Biochem Pharmacol 40: 499-506, 1990) will examine by computer-aided conformational analysis the parameters (drug-phospholipid energy of interaction, position of the drug in a monolayer and its accessibility to the aqueous phase) which may be important for these effects. Mol Microbiol, 1990 Aug, 4(8), 1227 - 32 What are antibiotics? Archaic functions for modern activities; Davies J; Secondary metabolites are proposed to have played important roles in the evolution of the reactions of living forms on earth, in effecting and modulating reactions during biochemical evolution by chemical and structural interaction with 'receptor' sites in primitive macromolecular templates . For example, in the evolution of the translation system, as the polymerizing reactions became more complex and proteins became involved, the low molecular-weight effectors were functionally replaced by polypeptides, but retained their ability to interact with receptor sites in nucleic acids and proteins . Many of these low molecular-weight effectors now play a different role, that of antagonists, by interacting with the original receptor sites in macromolecular structures; this explains their contemporary activity as antibiotics. Yakugaku Zasshi, 1990 Aug, 110(8), 523 - 46 {Stereoselective synthesis of macrolide and polyether antibiotics}; Yonemitsu O; In order to establish a common methodology for the highly stereoselective and efficient synthesis of macrolide and polyether antibiotics, two macrolide aglycons, 12-membered ring methynolide and 16-membered ring tylonolide, were first synthesized mainly from D-glucose, with the aid of 4-methoxybenzyl (MPM) type protecting groups and construction of three consecutive chiral centers, via the syntheses of respective fragments followed by their coupling (Yamaguchi's esterification) and cyclization (Wittig-Horner reaction) . This method was extended to the synthesis of 14-membered ring pikronolide and, together with conformational analysis and control of macrolide rings, some typical 16-membered ring aglycons such as carbonolides, leuconolides, maridonolides, etc . Erythronolide A was also synthesized via an extremely efficient macrolactonization by virtue of conformational control and super activation of a seco-acid . For the synthesis of polyether antibiotics a new synthetic method of substituted tetrahydrofuran and -pyran rings was first established via a cyclization of styryl derivatives by acid catalyzed and/or chelation controlled reactions under kinetic and/or thermodynamic conditions . Highly complex polyether salinomycin was synthesized via coupling of three fragments prepared from D-glucose, D-mannitol, and ethyl L-lactate essentially by the same method developed in the synthesis of macrolides . In this synthesis the MPM type protecting groups acted a crucial role . The synthesis of isolasalocid A was completed via isolasalocid ketone, in which two tetrahydrofuran rings were constructed by the above acid catalyzed and chelation controlled cyclizations . Similarly lasalocid A was synthesized from D-glucose via lasalocid ketone. J Gen Microbiol, 1990 Aug, 136 ( Pt 8), 1447 - 54 Biosynthesis of oleandomycin by Streptomyces antibioticus: influence of nutritional conditions and development of resistance; Vilches C et al.; The influence of different nutritional compounds on oleandomycin biosynthesis by Streptomyces antibioticus was studied, resulting in the design of a chemically defined medium for production of the antibiotic . Of the variety of carbon and nitrogen compounds tested, fructose and aspartic acid (carbon and nitrogen sources, respectively) supported the highest oleandomycin titres . Addition of propionate but not acetate, both precursors of the skeleton of the macrolide lactone ring, stimulated the biosynthesis of the antibiotic . Oleandomycin biosynthesis was repressed by glucose but not by phosphate . S . antibioticus develops oleandomycin resistance shortly before the antibiotic begins to be synthesized, showing a triphasic pattern of resistance: spores and producing mycelium are resistant, while non-producing mycelium is sensitive. Arerugi, 1990 Aug, 39(8), 696 - 700 {Studies on antibiotic skin testing}; Matsumura Y et al.; Commercially available antibiotics for injection are supplied with test ampules . Users are instructed to dissolve them to make 300 micrograms/ml solution for intradermal pretests to avoid allergic reactions . Sometimes this concentration is too low to prevent anaphylactic reactions . In the present study, we tried to find the maximum concentration for the intradermal tests which would have high sensitivity without giving nonspecific, false positive reactions . We investigated intradermal tests with cephalothin (CET) in a patient who suffered from anaphylaxis after drip infusion with CET, although she was judged to be negative to CET by the usual intradermal test prior to the infusion . Her CET skin test was negative at a concentration of 150 micrograms/ml and positive at 300 micrograms/ml 6 weeks after anaphylaxis, but negative at 300 micrograms/ml and positive at 1000 micrograms/ml 4 and 7 years after anaphylaxis . Prick tests were always negative, even with the maximum soluble concentration of CET, 200 mg/ml . Nonspecific reactions to intradermal tests at concentrations as high as 1000 micrograms/ml were examined with 20 kinds of penicillins and cephems in 51 healthy subjects without histories of drug allergies . Very few false positive reactions were observed, except in 5 out of 24 cases with cefotiam . Intradermal tests at 3000 micrograms/ml, however, frequently resulted in nonspecific reactions . We conclude that 1000 micrograms/ml, not 300 micrograms/ml solutions should be used for intradermal tests to prevent allergic reactions to the injection of antibiotics. Acta Paediatr Scand, 1990 Aug-Sep, 79(8-9), 838 - 46 Use of medical care and antibiotics among preschool children in different day care settings; Rasmussen F et al.; The use of medical care among 880 1-5 year olds in different day care settings was studied using register information on physician visits, purchases of antibiotics and municipal day care in 1984 . The unit of analysis was months in the different day care settings and not children . The rates of physician visits were 1.4 to 1.8 times higher for acute upper respiratory tract infections and all acute infections and 2 to 3 times higher for secretory otitis media during day care centre months and family day care months as compared to home care months . The rate of visits for bronchial asthma was 5 times higher during day care centre months than during home care months . No differences were found between day care centre months and family day care months with respect to the rates of physician visits for acute upper respiratory tract infections, acute otitis media and all acute infections . Among children in family day care, the daily number of hours in day care, and size, average age and age homogeneity of the groups were not significantly associated with rates of visits for all acute infections or purchases of antibiotics. Jpn J Pharmacol, 1990 Aug, 53(4), 463 - 72 Specific metabolic activation of FK973, a new antitumor antibiotic, in L1210 leukemia cells; Masuda K et al.; FK973 (11-acetyl-8-carbamoyloxymethyl-4-formyl-14-oxa-1,11- diazatetracyclo{7.4.1.O2,7O10,12}tetradeca-2,4,6-trien -6,9-diyl diacetate), a new substituted dihydrobenzoxazine, has potent cytotoxic and antitumor effects on murine and human tumors in vivo and in vitro, and forms interstrand DNA-DNA and DNA-protein cross-links after being activated in the cytoplasm . In this study, the mechanism(s) by which FK973 is activated in the cytoplasm of in vitro cultured murine L1210 leukemia cells were studied using compounds that affect monoamine oxidase . When the cells were incubated with an antitumor drug and the compounds, tranylcypromine, benzylamine, phenylethylamine and tyramine of the many compounds tested reduced the cytotoxicity of FK973, but not that of mitomycin C or cisplatin . These compounds also suppressed the formation of interstrand DNA-DNA cross-links with FK973 in the cells, but did not suppress cross-links with mitomycin C or cisplatin . The incorporation of 14C-FK973 into the cells was not affected by these compounds . The results suggest that FK973 is activated by some drug-metabolic system(s) in the cytoplasm to form interstrand DNA-DNA cross-links, and induces cytotoxicity against the cells . This activation of FK973 in the cytoplasm is discussed in connection with the drug-metabolic system(s) in relation to the structures of the compounds. J Antibiot (Tokyo), 1990 Aug, 43(8), 967 - 76 Chemical and biological properties of rubiginone, a complex of new antibiotics with vincristine-cytotoxicity potentiating activity; Oka M et al.; A novel complex of isotetracenone (angucyclinone) group antibiotics was discovered from the cultured broth of Streptomyces griseorubiginosus No . Q144-2 . The antibiotic consisted of six related factors, designated rubiginones A1, A2, B1, B2, C1 and C2 . They significantly potentiated cytotoxicity of vincristine (VCR) against VCR-resistant P388 leukemia and Moser cells. J Antibiot (Tokyo), 1990 Aug, 43(8), 961 - 6 Himastatin, a new antitumor antibiotic from Streptomyces hygroscopicus . II . Isolation and characterization; Leet JE et al.; The novel antitumor antibiotic himastatin was isolated from cultured broth of Streptomyces hygroscopicus (ATCC 53653) and purified by vacuum liquid chromatography, column chromatography, and crystallization . Degradation and spectroscopic studies have shown that himastatin contains valine, leucine, threonine, alpha-hydroxyisovaleric acid, 5-hydroxypiperazic acid and a dimeric hexahydropyrroloindole system. J Antibiot (Tokyo), 1990 Aug, 43(8), 948 - 55 YS-822A, a new polyene macrolide antibiotic . I . Production, isolation, characterization and biological properties; Itoh A et al.; A new polyene macrolide antibiotic, YS-822A was isolated from the culture filtrate of a mutant strain H-8 of Streptoverticillium eurocidicum var . asterocidicus S-822 . Whereas the original S-822 strain produced not only YS-822 substances but also teleocidin as by-product which is well-known as a strong carcinogenic promoter, the mutagenized H-8 strain produced the antibiotic with only a trace amount of teleocidin . Chemical and biological characterizations of the antibiotic revealed that YS-822A (molecular formula: C37H59NO14) is a new polyene macrolide with a wide antifungal spectrum and a low acute toxicity. Exp Mol Pathol, 1990 Aug, 53(1), 11 - 33 Interaction of anthracyclinic antibiotics with cytoskeletal components of cultured carcinoma cells (CG5); Molinari A et al.; The effects of doxorubicin (adriamycin, ADR) and daunorubicin (daunomycin, DAU), two anthracyclinic antibiotics, on a human breast carcinoma cell line (CG5) were studied by cytochemical and morphological methods . Both ADR and DAU were capable of inducing the multinucleation and spreading phenomena, associated with a decrease of the cell growth rate . DAU appeared to be more effective than ADR at the tested concentrations (10(-5), 5 x 10(-5) mM), in affecting the cell growth as well as in inducing multinucleation . As revealed by scanning electron microscopy, spreading and multinucleation were accompanied by a remarkable redistribution of surface structures . Moreover, a dose- and time-dependent rearrangement of the underlying cytoskeletal components was clearly detected . In addition, both ADR and DAU at 5 x 10(-5) mM seemed to favor the rebuilding of microtubules after treatment with colcemid, while a higher dose (10(-4) mM) exerted the opposite effect . Furthermore, both anthracyclines prevented the action of the antimicrotubular agent . When recovered after treatment with cytochalasin B, in presence of ADR (or DAU) (5 x 10(-5), 10(-4) mM), cells showed a microfilament pattern rearranged differently as compared to that of cells recovered in anthracycline-free medium . The results reported here strongly suggest the involvement of actin and tubulin in CG5 cell response to ADR and DAU treatments . Thus, the cytoskeletal apparatus is confirmed as another target involved in the mechanism of action of anthracyclines. FEBS Lett, 1990 Aug 1, 268(2), 405 - 7 Antibiotics--cloning of biosynthetic pathways; Kleinkauf H et al.; Biosynthetic pathways leading to antibiotics have often been found to be clustered, and new organizational forms of multifunctional enzymes have been discovered . Such polyenzymes accomplish the synthesis of complex metabolites such as peptides or polyketides by a sequence of enzymatic reactions . So, reactions leading to the tripeptide precursor of beta-lactam antibiotics, ACV, or to the cycloundecapeptide cyclosporine have been fused into single polypeptide chain synthetases, respectively . In certain isofunctional sites restricted similarities have been detected. Antibiot Khimioter, 1990 Aug, 35(8), 9 - 11 {High-molecular polyphosphates and pyrophosphate in cyclosporin- producing Tolypocladium sp . and their role in the processes of growth and antibiotic synthesis}; Sotnikova IV et al.; The contents of high-energy phosphorous compounds, i.e . three fractions of polyphosphates, pyrophosphate, and ATP were determined in isogenic strains of Tolypocladium sp . differing in cyclosporine production levels . The content of polyphosphates was 1 to 2 orders of magnitude greater than that of pyrophosphate or ATP and did not depend on the strain productivity . During the period of the mycelial intensive growth and at the beginning of antibiotic synthesis, the level of polyphosphates lowered 2-3-fold and the content of pyrophosphate markedly decreased as well . The activities of polyphosphatase and pyrophosphatase during the culture growth and cyclosporine biosynthesis was higher in the highly productive strain. Hindustan Antibiot Bull, 1990 Aug-Nov, 32(3-4), 81 - 3 In vitro activity of certain antibiotics against dermatophytes; Dixit AK et al.; The in vitro effect of antibiotics i.e . Hamycin, Griseofulvin and Mycostatin against Microsporum gypseum and M . fulvum showed that hamycin was comparatively less inhibitory to M . fulvum . Complete inhibition in mycelial growth and sporulation of these two dermatophytes was observed by Mycostatin at its 1000 micrograms/ml conc . after 8 days . M . fulvum did not sporulate at higher concentration of griseofulvin . However, griseofulvin completely inhibited the sporulation in M . gypseum at all the concentration of this drug, but mycelial growth of M . fulvum and M . gypseum were significantly inhibited . Mycostatin was found more inhibitory to these dermatophytes in comparison to hamycin and griseofulvin. Cesk Otolaryngol, 1990 Aug, 39(4), 191 - 4 {Rational antibiotic therapy in ORL oncologic surgery}; Sibl O et al.; The decisive point is the suitable time of antibiotic administration, their combination and possibility to extend the surgical repertoire by prevention in particular of general complications . Wound healing is more rapid, and intended adjuvant treatment can, due to the reduce period of wound healing, be applied much sooner . It is more effective and the attainment of target structures by the administered drugs is not blocked by prolonged processes which are sometimes associated with fibrosis, scars and regressive tissue changes. Klin Med (Mosk), 1990 Aug, 68(8), 83 - 5 {Antibiotics as proteolysis inhibitors in the stomach}; Gorshkov VA et al.; The study was made of antibiotics action on hydrolysis of coagulated protein in gastric juice . It was established that antibiotics can produce inhibition of protein proteolysis in gastric juice . The highest antiprotease activity was reported for cephalosporins , rifampicin and penicillins, the lowest for tetracycline++ . Antiprotease activity of antibiotics should be taken into consideration when defining their therapeutic effect in peptic ulcer. Endod Dent Traumatol, 1990 Aug, 6(4), 157 - 69 Pulp revascularization in reimplanted immature monkey incisors--predictability and the effect of antibiotic systemic prophylaxis; Cvek M et al.; In 32 monkeys 105 immature maxillary incisors were extracted and reimplanted either immediately or after 30 or 60 min wet or dry storage . Of the monkeys, 17 (group I) did not receive and 15 (group II) received prophylactic treatment with 4 mg/kg doxycycline before extraction and 2 mg/kg for 5 d after reimplantation . The observation time varied from 6 to 8 weeks . After being histologically processed, the material was evaluated with respect to the amount of vital tissue and presence of micro-organisms in the pulpal lumen . A comparison revealed no difference in the results between the groups . The results were therefore pooled and statistically analysed with respect to the significance of apical foramen width, extra-alveolar time, wet or dry storage and presence of micro-organisms in the pulpal lumen for the occurrence of complete pulp revascularization (CPR) . The overall frequency of CPR was 18% . Log-linear analyses (SAS, 1985) of the material as a whole or of separate parameters consistently revealed a relationship between presence of micro-organisms and absence of CPR (P = 0.0001) . A higher frequency of CPR and a lower frequency of micro-organisms (P = 0.05) was found only for the group of immediately reimplanted teeth . The presence of micro-organisms could be explained for 61 teeth . In 27 of these, blood clots containing bacteria in the apical portion of pulpal lumen indicated contamination during the extra-alveolar time, while in 34, the micro-organisms originated from plaque covered mechanical damage in the cervical part of the root surface. Enzyme Microb Technol, 1990 Aug, 12(8), 564 - 70 Effect of intercalating dyes on the production of antibiotics by Micromonospora rosaria and Micromonospora purpurea; Kim KS et al.; The effect of treatment with various intercalating dyes on the ability to produce antibiotics in Micromonospora rosaria and Micromonospora purpurea was studied . Treatment with acriflavine resulted in a high frequency loss of antibiotic productivity in both species . In M . rosaria, the loss of antibiotic-producing ability appeared to be strain-dependent . In M . purpurea, up to 90% of colonies were found to have lost gentamicin-producing ability when protoplasts were used in the test . These antibiotic-nonproducing strains were further studied . The following observations were made: (1) Unlike the producing ability, the resistance to the antibiotics is a very stable character in both species . (2) Protoplast fusion analysis indicates that rosamicin-nonproducing characteristics of MR 217-AF2 and MR 217-AF3 strains induced by the acriflavine treatment is due to chromosomal mutation or rearrangement but not to loss of a plasmid . (3) Gentamicin-nonproducing strains of M . purpurea responded differently to the supplementation of streptamine or DOS in the culture medium . When supplemented with streptamine or DOS, some of these strains regained the ability to produce antibiotic, showing that the biosynthesis of intermediate was affected in these strains. Cancer Res, 1990 Jul 15, 50(14), 4260 - 6 Anthracycline antibiotics with high liposome entrapment: structural features and biological activity; Perez-Soler R et al.; We evaluated the entrapment of 21 different water-insoluble aglycones or anthracycline antibiotics in multilamellar liposomes composed of dimyristoyl phosphatidyl choline and dimyristoyl phosphatidyl glycerol at a 7:3 molar ratio . The drug:lipid weight ratio was 1:15 to 1:50 . The different analogues tested were modified at position 4 in the aglycone portion (4-demethoxy) and/or positions 2' (halo), 3' (hydroxy, acetoxy), or 4' (epi, acetoxy) in the sugar portion . The entrapment efficiency was assessed by measuring the amount of free drug remaining in the supernatant after centrifugation of the liposomes and by direct examination of the pellets by fluorescent microscopy . Optimal entrapment (greater than 98%) was observed with only four compounds: 4-demethoxyadriamycinone; 2'-iododaunorubicin; 4-demethoxydaunorubicin; and 2'-iodo-3'-hydroxy-4'-epi-4-demethoxydoxorubicin (Compound 22) . All other compounds showed significant drug precipitation outside the multilamellar vesicles when observed by fluorescent microscopy . Compound 22, entrapped in liposomes, was evaluated in vivo against i.p . L-1210 leukemia by the i.p . route, and liver metastases of M5076 reticulosarcoma by the i.v . route . In both models, liposome-entrapped Compound 22 was more active than doxorubicin at the optimal dose {median survival (given in percentage) of treated to control animals was for L-1210, greater than 600 versus 212; for M5076, 200 versus 133} . 4-Demethoxy and 2'-iodo are structural modifications that markedly enhance the affinity of anthracycline antibiotics for lipid bilayers without compromising biological activity . These findings will serve as a guideline to obtain liposome-anthracycline preparations, with optimal formulation characteristics, enhanced tumor-targeting properties, and non-cross-resistance with doxorubicin. Alcohol, 1990 Jul-Aug, 7(4), 295 - 8 Ferrous sulfate combined with ascorbic acid does not significantly reduce acetaldehyde accumulation in the blood of alcoholized rats treated with disulfiram or betalactam antibiotics; Freundt KJ et al.; Adult female SPF Sprague-Dawley rats treated orally by gavage with disulfiram (1 g/kg b.wt.) or betalactam antibiotics (3.38 mmol/kg b.wt.) with a 1-methyltetrazole-5-thiol side chain (cefmenoxime, latamoxef, cefotetan, cefoperazone, cefamandole) produced a marked, statistically significant rise of acetaldehyde in the blood 1 and 3 hr following IP administration of ethanol {2 g/kg b.wt., 20% (g/v) solution} . This accumulation of blood acetaldehyde remained unchanged or was reduced only very slightly by a mixture of iron sulfate {Fe(II)SO4.7H2O, 2.64 mg/kg b.wt.} and ascorbic acid (6.67 mg/kg b.wt.) injected intravenously . This slight decrease is considered to be due to a formation of a complex between ferrous sulfate and agents (disulfiram and the betalactam antibiotics as well as their metabolites) producing acetaldehyde by inhibition of acetaldehyde metabolizing enzymes . A possible coaction of ascorbic acid cannot be explained satisfactorily; ascorbic acid may support cellular redox potentials . The combination of ferrous sulfate and ascorbic acid was used for examination since both chemicals are recommended to reduce adverse symptoms of an ethanol incompatibility reaction in the course of a therapy with the mentioned antibiotics or disulfiram . Since acetaldehyde augmentation in the blood is regarded as a cause of complaints and because the acetaldehyde rise was not depressed significantly by ferrous sulfate and ascorbic acid it can be concluded that these two agents are not potent enough for a rational therapy of ethanol incompatibility symptoms initiated by the investigated drugs. J Antibiot (Tokyo), 1990 Jul, 43(7), 890 - 6 The structure of tautomycetin, a dialkylmaleic anhydride antibiotic; Cheng XC et al.; The chemical structure of tautomycetin (C33H50O10) was determined by chemical degradation and spectroscopic evidence . Tautomycetin exists in methanol-buffer solution (1% diethylamine-formic acid, pH 7.3) as an equilibrium mixture of a 2,3-dialkylmaleic anhydride and its dicarboxylic acid . The structure of tautomycetin is similar to tautomycin in many respects. J Antibiot (Tokyo), 1990 Jul, 43(7), 809 - 19 The structure of tautomycin, a dialkylmaleic anhydride antibiotic; Cheng XC et al.; The chemical structure of tautomycin (C41H66O13) was determined by chemical degradation, spectroscopic analysis and 2D INADEQUATE of tautomycin labeled with {1,2-13C}acetate . Tautomycin exists in methanol-buffer solution (1% diethylamine-formic acid, pH 7.3) as an equilibrium mixture of a 2,3-dialkylmaleic anhydride and its dicarboxylic acid in a ratio of approximately 5:4. J Antibiot (Tokyo), 1990 Jul, 43(7), 755 - 62 Pradimicins A, B and C: new antifungal antibiotics . I . Taxonomy, production, isolation and physico-chemical properties; Tomita K et al.; New antifungal antibiotics, pradimicins A, B and C were isolated from the culture broth of actinomycete strains proposed as Actinomadura hibisca . They are orange to red pigments containing a benzo{a}naphthacenequinone chromophore substituted with a D-alanine, an aminosugar and a D-xylose (pradimicins A and C). J Antibiot (Tokyo), 1990 Jul, 43(7), 748 - 54 A novel antifungal antibiotic, FR-900848 . I . Production, isolation, physico-chemical and biological properties; Yoshida M et al.; Streptoverticillium fervens produced a new antibiotic, FR-900848, which has a high specific activity against filamentous fungi . Purified by solvent extraction and column chromatography, the compound appears as colorless crystals . Its structure is C32H43N3O6, which consists of 5'-amino-5'-deoxy-5,6-dihydrouridine with an unsaturated fatty acid having unprecedented four serial and one isolated cyclopropane rings. Urol Nefrol (Mosk), 1990 Jul-Aug, (4), 17 - 20 {Postoperative endolymphatic antibiotic therapy in urology patients with suppurative-inflammatory diseases}; Ukhal' MI et al.; In 54 patients with pyoinflammatory processes in the urogenital system, the efficacy of endolymphatic antibiotic therapy was investigated after surgical interventions into these organs along with administration of antibiotics just into the inguinal lymph node . To administer antibiotics, separation and drainage of the inguinal lymph node were conducted concurrently with surgical interventions in 26 patients for pyoinflammatory processes in the epididymis, prostate, and kidneys . In the other group (n-28), the inguinal lymph node was drained on days 4 to 5 of postoperative interventions due to the progression of an acute infectious inflammation in the affected organs and wounds . The efficacy of endolymphatic antibiotic therapy was evaluated by using clinical, laboratory, cytochemical, and immunological criteria . The drainage of inguinal lymph nodes in combination with aminoglycoside and cephalosporin antibiotics given in the postoperative period proved to be a safe and effective mode of treatment of pyoinflammatory processes in urogenital organs and wounds. Andrologia, 1990 Jul-Aug, 22(4), 355 - 60 {Mollicutes in male infertility: is antibiotic therapy indicated?}; Sanchez R et al.; Mollicutes are frequently isolated from sperma of infertile men . The potential effect on the fertility of mollicute infection is controversial as is antibiotic therapy . In our andrological patients, the prevalence of mollicutes is approximately 10% . To evaluate the benefit of antibiotic therapy, we investigated two groups of patients: group 1-patients with positive or negative mollicute cultures and normal spermiogram; morphological changes on spermatozoa were particularly evaluated (n = 40); group 2 - patients with positive mollicute cultures treated with doxycycline or erythromycin . Sperm parameters were analysed before and after treatment (n = 20) . When infected and non-infected sperma from group 1 were compared, the only difference found was an alteration of the sperm tail (p less than 0.005) . Light microscopy and electron microscopy (EM) often revealed coiled tails which were probably due to adhesion of mollicutes (EM) . The most frequently observed pathology in group 2 was found in patients with teratoasthenozoospermia . Compared with the post-therapy spermiogram, a significant difference was only observed in spermatozoal morphology (p less than 0.005) . Therefore, we conclude that mollicutes produce important alterations in the human spermatozoal morphology, especially in the tail which appears in a spiral form . Since teratozoospermia is considered to be an important factor of infertility in man, antibiotic therapy is recommended in cases of mollicute involvement. Acta Neurol Scand, 1990 Jul, 82(1), 59 - 67 Follow-up of antibiotically treated and untreated neuroborreliosis; Kruger H et al.; Follow-up of 57 patients who suffered from antibiotically untreated acute, monophasic neuroborreliosis 5 to 27 years ago shows no significant difference in comparison with the follow-up of 66 patients who suffered from antibiotically treated acute, monophasic neuroborreliosis during the last 5 years . In both groups, the involution of clinical symptoms and the normalization of pathological CSF findings were nearly identical . We found no significant difference of sequelae between the groups . Following acute neuroborreliosis, neither the antibiotically untreated nor the antibiotically treated patients developed chronic neuroborreliosis . Only in rare cases of primary chronic neuroborreliosis with CNS involvement did we observe convincing effects of antibiotics, which were given mostly in combination with glucocorticosteroids. Eur J Clin Microbiol Infect Dis, 1990 Jul, 9(7), 523 - 9 The design of clinical trials with antibiotics; Norrby SR; Clinical trials to test antibiotics are normally of a less than satisfactory quality . Examples of common errors in the design and execution of trials with antibiotics are inclusion of too few patients to allow conclusions to be drawn, open uncontrolled design leading to a risk of considerable investigator bias, and inclusion of heterogeneous patient samples . This article suggests minimum requirements for antibiotic studies . Guidelines for such trials are needed and should have the widest possible international application in order to permit studies involving centres in various countries and to reduce the costs for development of new drugs. Eur J Clin Microbiol Infect Dis, 1990 Jul, 9(7), 472 - 8 Animal models as predictors of the safety and efficacy of antibiotics; Zak O et al.; As opposed to the testing of safety, the testing of the efficacy of antibiotics in animals is not specified in any directives or guidelines and not explicitly required by regulatory authorities . There exists, however, no doubt that in the evaluation of new compounds testing of both safety and efficacy forms an essential link between in vitro tests and clinical trials . It is inconceivable that clinicians would be prepared to conduct a trial in patients without evidence of the efficacy of the antibiotic in question in an appropriate animal model of infection . Both the models for testing safety and those for testing efficacy suffer from a number of shortcomings . If investigators are aware of these deficiencies and take them into account when interpreting the results, the predictive value of the models can be significantly enhanced. Clin Podiatr Med Surg, 1990 Jul, 7(3), 523 - 44 Use of antibiotic-loaded bone cement in the management of common infections of the foot and ankle; Jacobs AM et al.; Antibiotic-loaded bone cement is a useful adjunct in the management of chronic osteomyelitis and in the prevention of recurrent osteomyelitis after an initial attack . Additionally, antibiotic-loaded bone cement stimulated the formation of granulation tissue in excess of that which would normally be expected . Our experience has been consistent with others' experience, which suggests that the use of antibiotic-loaded bone cement is an effective means of reducing the length of hospitalization and the cost usually associated with traditional methods in the management of bone and soft-tissue infections. Ther Umsch, 1990 Jul, 47(7), 561 - 8 {Preventive use of antibiotics in surgery: a review}; Picard G et al.; As a rule, prophylactic antibiotics should only be given pre- or perioperatively as a single shot . Cephalosporins of the first and second generation are still quite effective and appear to be the most widely used drugs for this purpose . In some cases a second drug, like i.e . metronidazole, can be added . For each surgical specialty, the most appropriate prophylactic regimen is discussed. J Ophthalmic Nurs Technol, 1990 Jul-Aug, 9(4), 145 - 51 Confusion and the patient on an intensive topical ocular antibiotic regimen: a case analysis; Orticio LP; Round-the-clock instillation of antibiotics disrupts the sleep-wake cycle and may concomitantly result in an acute confusional state . Behavioral manifestations can be attributed to alterations in the sleep-wake cycle; sensory/environmental deficit related to hospitalization; alterations in nutrition and electrolyte balance; age; and medication . Patients at high risk for confusion must be identified and given priority attention . Acute confusion, if not detected and addressed early, may have serious consequences as threatening as the loss of sight. J Am Podiatr Med Assoc, 1990 Jul, 80(7), 354 - 9 Development and application of antibiotic-loaded bone cement beads; Stabile DE et al.; The authors presented an overview of the development of antibiotic-loaded bone cement beads and their indications for usage, method of application, advantages, disadvantages, and causes of failure . This method of treatment for bone and soft tissue infections of the foot is not a panacea and should be used only in selected cases . The vascular status and the physiologic ability of the patient to heal a peripheral wound or infection are the basis for the success of this method of therapy . European literature makes little mention of adjunctive systemic antibiotic therapy with local antibiotic-loaded bone cement bead use . It is the authors' opinion that clinical judgment should be used to determine the necessity for such therapy. Eur J Obstet Gynecol Reprod Biol, 1990 Jul-Aug, 36(1-2), 69 - 74 Suspected postpartum endometritis: a controlled clinical trial of single-agent antibiotic therapy with Amox-CA (Augmentin) vs . ampicillin-metronidazole +/- aminoglycoside; Fernandez H et al.; Endometritis is the commonest postpartum complication and is one of the leading causes of maternal morbidity, if not mortality . The object of the present clinical trial was to assess the efficiency of single-agent therapy with Amox-CA (Augmentin) (formulation which includes a beta-lactamase inhibitor), against standard treatment which necessarily combines two or three antibiotics depending on the clinical severity of the case . 101 patients were evaluated in this comparative prospective randomized study . The mild forms were defined by a temperature between 37.9 and 38.4 degrees C and the severe forms by a temperature of more than 38.5 degrees C (which alone required treatment with three antibiotics) . The time until the return of apyrexia and the clinical cure rate, as well as duration of treatment, were identical in both groups . Tolerance was good: no side effect requiring discontinuation of treatment occurred . In the population value, the use of a single-agent therapy with amoxycillin/clavulanic acid is not significantly different from a double or triple-agent regimen, and the convenience is increase. Antibiot Khimioter, 1990 Jul, 35(7), 41 - 3 {The main principles of biophysical and chemical purification of highly concentrated liquid waste from antibiotic manufacture}; Faingol'd ZL; An approach to investigation of multicomponent systems such as plants designed for biophysicochemical purification of liquid sewage including diverse interconnected technological apparatus operating under routine conditions is described . A system analysis applied to a simplified technological scheme for collecting treated liquid sewage was used. Antibiot Khimioter, 1990 Jul, 35(7), 35 - 8 {Increasing the effectiveness of antibiotic therapy by correcting immunologic disorders with vitamin A in patients with brucellosis}; Kurmanova KB et al.; Experimental studies and clinical trials were performed on possible increase of antibiotic therapy efficacy in brucellosis patients by correction of the immunity disorders with vitamin A . It was experimentally shown that vitamin A increased cellular immunity and accelerated sanation of guinea pigs sensitized with Brucella abortus 19 BA . The clinical trials demonstrated that the use of vitamin A in a dose of 33,000 IU thrice a day for 10 to 12 days during the complex treatment of patients with acute (36 persons) and subacute (57 persons) brucellosis lowered the average period of manifestation of the disease clinical signs and formation of the antibodies, increased the skin allergic sensitivity, the lymphocyte blast cell transformation, the total number and subpopulations of the active T-cells, theophylline-resistant lymphocytes, phagocytic and metabolic activity of neutrophils, showed 1.5- and 2-fold increased in the frequency of the infection transformation into a chronic process in patients with acute or subacute brucellosis, respectively. Br J Nutr, 1990 Jul, 64(1), 59 - 70 The influence of inclusion of either an antibiotic or a probiotic in the diet on the development of digestive enzyme activity in the pig; Collington GK et al.; The aim of the present experiment was to determine the influence of either probiotic or antibiotic inclusion in the diets of pigs from birth on the development of enzyme activity in the small intestine . Pigs were fed on creep feed and grower diets containing either a probiotic, an antibiotic or no added growth promoter . At 7, 17, 42 and 80 d of age pigs from each treatment group were sampled to investigate the development of carbohydrase and peptidase activity in the mucosa at five sites along the small intestine . Inclusion of either the probiotic or antibiotic had a significant effect on the development of sucrase (sucrose alpha-D-glucohydrolase; EC 3.2.1.48), lactase (beta-D-galactoside galactohydrolase; EC 3.2.1.23) and tripeptidase (EC 3.4.11.4) activities before weaning but had no effect on depeptidase (EC 3.14.13.11) activity . The study of the distribution of enzyme activity along the small intestine showed significant differences between the proximal and distal sections associated with weaning. J Bacteriol, 1990 Jul, 172(7), 3772 - 9 The ermC leader peptide: amino acid alterations leading to differential efficiency of induction by macrolide-lincosamide-streptogramin B antibiotics; Mayford M et al.; The inducibility of ermC by erythromycin, megalomicin, and celesticetin was tested with both wild-type ermC and several regulatory mutants altered in the 19-amino-acid-residue leader peptide, MGIFSIFVISTVHYQP NKK . In the model test system that was used, the ErmC methylase was translationally fused to beta-galactosidase . Mutational alterations that mapped in the interval encoding Phe-4 through Ile-9 of the leader peptide not only affected induction by individual antibiotics, but did so differentially . The subset of mutations that affected inducibility by the two macrolides erythromycin and megalomicin overlapped and were distinct from the subset of mutations that affected induction by celesticetin . These studies provide a model system for experimentally varying the relative efficiencies with which different antibiotics induce the expression of ermC . The possibility that antibiotics with inducing activity interact directly with the nascent leader peptide was tested by using a chemically synthesized decapeptide, MGIFSIFVIS--, attached at its C-terminus to a solid-phase support . This peptide, however, failed to bind erythromycin in vitro. Aust N Z J Surg, 1990 Jul, 60(7), 539 - 43 Systemic antibiotic regimens for acute cholecystitis treated by early cholecystectomy; Lau WY et al.; A total of 203 patients were randomized into a prospective trial to compare short (SC) versus long courses (LC) of systemic antibiotic for acute cholecystitis treated by early cholecystectomy . The initial pre-operative management was the same and all patients received 2 g of cefamandole intravenously just before operation . Two further doses of cefamandole 500 mg were given 6 and 12 h later for patients on SC while the antibiotic was continued at 500 mg at 6 h intervals for 7 days for patients on LC . Seven patients developed wound infection on SC compared with five patients with wound infection and an additional patient with a subphrenic abscess on LC (P greater than 0.05) . Thrombophlebitis related to intravenous antibiotic injections was more common in patients on LC (P less than 0.05) . Also, patients on LC had to stay statistically longer in hospital in order to complete the course of antibiotic (P less than 0.05) . We therefore recommend a SC to be used, as it is more cost-effective and causes fewer complications. Biotechnol Prog, 1990 Jul-Aug, 6(4), 266 - 72 Representation of phase equilibrium behavior of antibiotics; Zhu YZ et al.; The phase equilibrium behavior of biomolecules is important both in understanding the partition mechanisms and in the design and optimization of downstream recovery processes . Chen et al . (1989) proposed a molecular thermodynamic framework that successfully represents the liquid-solid equilibrium behavior of amino acids and small peptides as functions of temperature, ionic strength, solvent compositions, and pH . Based on this theoretical framework, this paper presents recent results in representing the liquid-solid equilibrium behavior (solubilities) and the liquid-liquid equilibrium behavior (phase partitioning) of beta-lactam antibiotics, which are amino acid derivatives and important chemotherapeutic agents. Trends Biotechnol, 1990 Jul, 8(7), 184 - 9 Phosphate control sequences involved in transcriptional regulation of antibiotic biosynthesis; Liras P et al.; The expression of genes encoding enzymes involved in antibiotic and other secondary metabolite biosynthesis is down-regulated by easily assimilable phosphate, carbon and nitrogen sources . Phosphate control of antibiotic production appears to act at the transcriptional level by a mechanism similar to that involved in control of phosphatases and other phosphate-regulated enzymes . A phosphate control (PC) sequence, strikingly similar to the phosphate control (pho) boxes of many bacterial genes, has been isolated from the phosphate regulated promoter that controls biosynthesis of the antibiotic candicidin, and characterized . From computer analysis of sequence data, PC sequences appear to be associated with promoter regions of several phosphate-controlled antibiotic biosynthetic genes. Biochem Biophys Res Commun, 1990 Jun 15, 169(2), 610 - 6 Inhibition of 3-hydroxy-3-methylglutaryl coenzyme A synthase by antibiotic 1233A and other beta-lactones; Mayer RJ et al.; 3-Hydroxy-3-methylglutaryl CoA synthase was shown to be inhibited in a time-dependent, irreversible manner by compounds containing the substituted beta-lactone functionality found in the natural product 1233A . The rate of inactivation (kinact) was found to approach the rate of catalysis (kcat) . The inactivation was irreversible over several hours . A related compound lacking the hydroxymethyl substituent on the beta-lactone ring is a reversible inhibitor and is competitive with respect to acetylCoA . The results are consistent with beta-lactone ring opening by the active site Cys to form an enzyme bound thioester. Br Dent J, 1990 Jun 9, 168(11), 446 - 7 Prophylactic antibiotics; Pogrel MA; The prescribing of antibiotics in the absence of infection has always been controversial and when the lawyers get involved as well, it becomes almost unmanageable . With this is mind, it might be useful to look at some of the problems we have with antibiotics in California. Antibiot Khimioter, 1990 Jun, 35(6), 43 - 5 {A case of successful antibiotic therapy of legionnaires' disease with lesions of the lungs and heart}; Zamotaev IP et al.; Pulmonary affections in patients with legionellosis are the main ones . The affections of the heart, gastrointestinal tract and other organs and systems are less frequent . Some characteristic features of the legionellosis clinical process in the case described are indicated . The torpid process of chronic bronchitis, the two-phase pattern of the disease, dyspnea at 3-4 month intervals, intermissions, edema and failure of complex therapy with antibiotics and cardiac glycosides provided a tentative diagnosis of Legionella pneumonia with affection of the myocardium . The importance of early serological diagnosis (enzyme immunoassay) was shown . A new approach to the treatment of legionellosis with cefuroxime was of interest. Vrach Delo, 1990 Jun, (6), 38 - 40 {The side effects of antibiotics in chronic bronchitis}; Pilipchuk VN; The author investigated the frequency and character of side-effects to penicillin, levomycetin, tetracycline in the treatment of 92 patients with different forms of chronic bronchitis . Clinically all side-effects were subdivided in dysbacteriosis, allergic, toxic and mixed . It was established that the high incidence of side-effects furthers allergization of the body and potentiation of bronchial spasm . That is why the employment of antibiotics in these cases is not indicated . The low incidence of side-effect of antibiotics in purulent bronchitis requires their use under thorough medical surveillance. Pathol Biol (Paris), 1990 Jun, 38(5 ( Pt 2)), 543 - 7 {Treatment of bone infection by plaster of Paris pellets impregnated with antibiotics}; Evrard J et al.; In two prospective clinical trials, the authors treated 83 chronic osteomyelitis from various origins by sequestrectomy completed with insertion of Plaster of Paris pellets impregnated with antibiotics . After a review of the experimental and clinical reports on the subjects, the authors give their results: 61.5% of healings and 38.5% of failures . Because of the small number of cases, it was not possible to find out an explanation for this fair results . However wide extension of the lesions, which is frequent in chronic haematogenous osteomyelitis, seems to be a contraindication to the technics . The authors conclude to the necessity of carrying up new experiments with new antibiotics and large series of patients in order to point out the righted indications of the method. S Afr J Surg, 1990 Jun, 28(2), 58 - 61 Do pre-operative antibiotics reach the operative field in amputation surgery for peripheral vascular disease? A pilot study; Mars M et al.; Amputation surgery in patients with peripheral vascular disease is associated with high revision and mortality rates . A prospective pilot study examined the intra-operative delivery of cefoxitin sodium to the amputation site, and used pre-operative transcutaneous oxygen pressure measurement to try to predict the tissue antibiotic levels at the amputation site . Antibiotic concentrations were measured in plasma and muscle from the amputation site at the time of amputation, and a significant difference in antibiotic distribution was found between healed and failed amputations . Transcutaneous oxygen pressures correlated with the antibiotic distribution. J Bacteriol, 1990 Jun, 172(6), 3108 - 16 Streptomyces genes involved in biosynthesis of the peptide antibiotic valinomycin; Perkins JB et al.; We have identified genes from Streptomyces levoris A-9 involved in the biosynthesis of the peptide antibiotic valinomycin . Two segments of chromosomal DNA were recovered from genomic libraries, constructed by using the low-copy-number plasmid pIJ922, by complementation of valinomycin-deficient (vlm) mutants of S . levoris A-9 . One set of plasmids restored valinomycin production to only one mutant, that carrying vlm-1, whereas a second set of plasmids restored productivity to seven vlm mutants, those carrying vlm-2 through vlm-8 . Additional complementation studies using subcloned restriction enzyme fragments showed that the vlm-1+ gene was contained within a 2.5-kilobase (kb) DNA region, whereas alleles vlm-2+ through vlm-8+ were contained in a 12-kb region, representing at least three genes . Physical mapping experiments based on the isolation of cosmid clones showed that the two vlm loci were 50 to 70 kb apart . Southern hybridization experiments demonstrated that the vlm-2+ gene cluster was highly conserved among other valinomycin-producing Streptomyces strains, whereas the vlm-1+ gene was ubiquitous among Streptomyces species tested . Increasing the copy number of the vlm-2+ gene cluster in S . levoris A-9 by the introduction of low-copy-number recombinant plasmids resulted in a concomitant increase in the level of valinomycin production. J Bacteriol, 1990 Jun, 172(6), 2962 - 9 Mutations in a new Streptomyces coelicolor locus which globally block antibiotic biosynthesis but not sporulation; Adamidis T et al.; Streptomyces coelicolor produces four known antibiotics . To define genetic elements that regulate antibiotic synthesis, we screened for mutations that visibly blocked synthesis of the two pigmented antibiotics and found that the mutant strains which we recovered were of two classes--double mutants and mutants in which all four antibiotics were blocked . The mutations in these multiply blocked strains define a new locus of S . coelicolor which we have named absA . The genetic location of absA, at 10 o'clock, is distinct from the locations of the antibiotic gene clusters and from other known mutations that affect antibiotic synthesis . The phenotype of the absA mutants suggests that all S . coelicolor antibiotic synthesis genes are subject to a common global regulation that is at least in part distinct from sporulation and that absA is a genetic component of the regulatory mechanism. Can J Microbiol, 1990 Jun, 36(6), 384 - 9 Interaction of iturin A, a lipopeptide antibiotic, with Saccharomyces cerevisiae cells: influence of the sterol membrane composition; Latoud C et al.; The binding of the membrane-active lipopeptide antibiotic iturin A to yeast cells was studied using radioactive iturin A . Saccharomyces cerevisiae had a maximum binding capacity of 5.6 x 10(9) molecules per single cell . The Scatchard plot of binding showed a biphasic profile, with a lower dissociation constant for small concentrations of iturin A . The break of slope at 30 microM iturin A corresponds to the micellization of antibiotic in solution . The binding is also dependent on the nature of the sterol present in the membrane . A mutant yeast strain with a membrane containing cholesterol instead of ergosterol showed the highest affinity for iturin A and the highest sensitivity to this antibiotic, as measured by K+ ion release . In contrast the presence of stigmasterol increased the resistance of the cells to iturin A. Mol Microbiol, 1990 Jun, 4(6), 1009 - 18 Construction of isogenic gonococci with variable porin structure: effects on susceptibility to human serum and antibiotics; Carbonetti N et al.; Protein I (PI) is the most abundant protein on