Hosp Formul, 1987 May, 22(5), 489 - 91 Antibiotic use review using the "target drug" method; Puckett F et al.; The "target drug" method was implemented to study the use of cefamandole and cefoxitin in a community hospital . There were no infectious disease specialists on staff, and restrictions on the use of individual agents was not a viable option for antibiotic control in this institution . Data was collected by the pharmacy staff and presented by the clinical pharmacy coordinator to individual medical specialties under the auspices of the P & T Committee . Appropriate literature was provided and discussed promoting the use of cefazolin in place of cefamandole and cefoxitin . As a result, cefamandole and cefoxitin use was reduced 41% and 12%, respectively, and cefazolin use increased fourfold . Net annual cost savings were in excess of $40,000, with costs of the pharmacists' time estimated to be $4,000. Biochemistry, 1987 Apr 7, 26(7), 1996 - 2000 Anthracycline antibiotics . Interaction with DNA and nucleosomes and inhibition of DNA synthesis; Fritzsche H et al.; We report studies of the interaction of four anthracycline antibiotics, iremycin (IM), daunomycin (DM), aclacinomycin A (AM), and violamycin B1 (VM), with naked DNA, nucleosomal core particles, and 175 base pair (bp) nucleosomes lacking histone H1 . In all cases the binding strength increases in the order IM less than DM approximately AM less than VM . The binding substrates increased in affinity for the drugs in the following order: core particles less than 175-bp nucleosomes less than DNA . The apparent DNA length increment per drug bound decreases in the progression IM greater than DM greater than AM greater than VM, the same serial order as is characterized by increasing binding affinity . Dichroism amplitude measurements show that for all drugs the long-wavelength absorbance transition moment is tilted by 26-29 degrees relative to the plane perpendicular to the helix axis; this angle probably corresponds to the long axis tilt of the intercalated chromophore . Finally, it was found that the ability of the drugs to inhibit DNA synthesis by Escherichia coli DNA polymerase I increases in the same order as their binding affinity. Circulation, 1987 Apr, 75(4), 768 - 77 Long-term follow-up of patients with the antibiotic-sterilized aortic homograft valve inserted freehand in the aortic position; Barratt-Boyes BG et al.; A series of 252 isolated aortic homograft valves in 248 patients have been followed for 9 to 16.5 years (mean 10.8) . The valves were sterilized in antibiotic solution and stored in a nutrient medium at 4 degrees C and were nonvital . There were 15 in-hospital deaths (6%) and a mortality of 2.7% in patients undergoing an elective first operation . Actuarial survival with the study valve in situ was 57% at 10 years and 38% at 14 years . Only 8.4% of the patients died late from homograft valve failure, chiefly because of failure to refer patients with endocarditis for reoperation or because reoperation was refused in elderly, frail subjects . Incompetence was the sole cause of valve failure and was due either to valve wear or endocarditis . Significant incompetence required reoperation . On actuarial analysis, freedom from significant incompetence for the entire group was 95% at 5 years, 78% at 10 years, and 42% at 14 years . Factors increasing the risk of significant incompetence due to valve wear on multivariate analysis were increasing donor valve age (greater than or equal to 55 years), recipient age (less than 15 years), and an aortic root diameter over 30 mm . Analysis of the patient group that excluded each of these variables (low-risk group), which comprised 61% of the study population, indicated freedom from significant incompetence due to valve wear of 98% at 5 years, 94% at 9 years, and 56% at 13 years. Jpn J Pharmacol, 1987 Apr, 43(4), 423 - 8 Suppressive effect of antibiotics on colony formation from human megakaryocyte progenitors (CFU-M) and granulocyte-macrophage progenitors (CFU-GM); Maruyama T et al.; beta-Lactam antibiotics, moxalactam (LMOX), cefotaxime (CTX), flomoxef (FMOX), cefamandole (CMD), carbenicillin (CBPC) and sulbenicillin (SBPC), suppressed colony formation from human megakaryocyte progenitors (CFU-M) and granulocyte-macrophage progenitors (CFU-GM) dose-dependently . The suppressive potencies for both progenitors were weakest for CBPC and SBPC, moderate for LMOX and FMOX, and strongest for CMD and CTX . The stainability of glycoprotein IIb/IIIa complex in the megakaryocyte colonies by the monoclonal antibody was decreased by LMOX and CTX . These data suggest that beta-lactam antibiotics directly suppress proliferation of CFU-M and CFU-GM. J Pharmacokinet Biopharm, 1987 Apr, 15(2), 191 - 202 The relation between plasma and tissue concentrations of antibiotics . Description of a method; Mattie H et al.; A mathematical approach to calculate rate constants of the distribution of antibiotics between plasma and tissue is described . The calculations are based on the assumption that the drug moves between plasma and tissue passively according to the law of diffusion . Corrections can be made for binding to tissue and to plasma proteins . Two mathematical procedures are compared, one based on multiple regression analysis of areas under the curves of the plasma and tissue concentrations and the other on simultaneous curve-fitting to plasma and tissue concentration curves . The method is illustrated for amoxycillin and erythromycin in murine thigh muscle . The half-life of distribution to this tissue is less than 2 min for amoxycillin and about 10 min for erythromycin, and the ratio between the free extracellular tissue concentration and the total tissue content is 4.25 for the former and 0.35 for the latter. Spine, 1987 Apr, 12(3), 254 - 6 Antibiotic penetration into rabbit nucleus pulposus; Eismont FJ et al.; A rabbit model was used to determine the penetration of four commonly used antibiotics (clindamycin, tobramycin, cephalothin, and oxacillin) into the nucleus pulposus after receiving an 8-hour course of intramuscular antibiotic injections . Clindamycin and tobramycin achieved therapeutic levels in the nucleus pulposus and both were present in greater than 50% of serum levels . Cephalothin was not detected in the nucleus pulposus and penetrated at less than 4% of serum levels at 1 hour after injection . The data were inconclusive regarding oxacillin penetration. Drug Intell Clin Pharm, 1987 Apr, 21(4), 322 - 9 Local treatment of respiratory infections with antibiotics; Stout SA et al.; Local administration of antibiotics for the treatment of respiratory infections has the potential advantage of reduced systemic toxicity and increased drug concentration at the site of infection . This article reviews the basic principles of pulmonary drug delivery using aerosols and the clinical efficacy of local antibiotic therapy of respiratory infections . Clinical studies have been conducted with locally administered aminoglycosides, penicillins, cephalosporins, and polypeptides . The results of these investigations and the pharmacokinetic aspects of pulmonary antibiotic delivery are summarized. Orthop Rev, 1987 Apr, 16(4), 209 - 14 The use of antibiotics in orthopaedic surgery . Total joint single- v multiple-dose prophylaxis; Hughes SP; In summary, I can assure you that if you give high-dose antibiotics at the time of operation, it is possible to show--either by bioassay techniques or by laboratory studies--that antibiotics reach the tissue at the time of operation . They lie within the fluid spaces in bone and are effective against the pathogenic organisms. Zentralbl Bakteriol Mikrobiol Hyg {A}, 1987 Apr, 264(1-2), 178 - 84 Antibiotic residues and R-plasmid selection: are in vitro methods good models? Corpet DE, Lumeau S. Three clones of E . coli, one of which was harbouring a tetracycline resistance plasmid were inoculated together into the stomach of axenic mice . Without antibiotic selective pressure, the R-Plasmid bearing strain became dominant in the faeces of mice, while the R-plasmid free strain was eliminated . When the R-plasmid bearing strain was given to mice 4 days after the inoculation with the R-plasmid free strain, it was repressed and remained at the stable level of 10(4.5) organisms per g of faeces . But a rapid spread of the R-plasmid was observed, tetracycline resistant bacteria become dominant within one day, and replace the tetracycline sensitive E . coli . The tetracycline resistance plasmid did not disadvantage the mediating strain in the gut, even in the absence of antibiotic pressure . In contrast Lebek and Egger (1983), studying the same strains in vitro, found that in a chemostat the plasmid bearing strain was overgrown by the plasmid free strain . These results strongly suggest that in vitro interactions between E . coli strains cannot be directly extrapolated to in vivo conditions . For the determination of the no-effect level of antibiotic residue on the selection of R-factor in the gut, studies should be made in vivo. J Antibiot (Tokyo), 1987 Apr, 40(4), 419 - 36 Paldimycins A and B and antibiotics 273a2 alpha and 273a2 beta . Synthesis and characterization; Argoudelis AD et al.; Paldimycin (antibiotic 273a1) and antibiotic 273a2 as well as their individual components, paldimycins A (273a1 alpha) and B (273a1 beta) and antibiotics 273a2 alpha and 273a2 beta were synthesized from paulomycin, paulomycin A and paulomycin B, respectively, by reacting with N-acetyl-L-cysteine . The semisynthetic antibiotics had chromatographic behavior (TLC, HPLC) and physical and chemical properties identical to the properties of the corresponding antibiotics produced by Streptomyces paulus. Antibiot Med Biotekhnol, 1987 Apr, 32(4), 288 - 91 {Cytopathogenic action of intact and antibiotic-altered populations of Bordetella pertussis on a human amnion cell culture}; Bakulina NA et al.; Cytopathogenic and adhesive action of intact B . pertussis population and population changed under the effect of antibiotics was studied comparatively . It was shown that the level and character of the changes in the cell culture of line FL human amnion depended on the antibiotic used in the experiments . Populations of B . pertussis changed under the effect of tetracycline had the highest cytopathogenic and adhesive activity, while the activity of the population changed under the effect of erythromycin was the least . The decrease in the cytopathogenic and adhesive activity of B . pertussis changed under the effect of erythromycin correlated with lowering of the toxicity and the loss of the main agglutinogenic factors of the surface of the bacteria cell wall . The increase in the toxicity of the population changed under the effect of tetracycline was accompanied by changes in the cytopathogenic and adhesive properties of the culture. J Chromatogr, 1987 Mar 27, 391(1), 207 - 17 Gas chromatographic-mass spectrometric determination of macrolide antibiotics in beef and pork using single ion monitoring; Takatsuki K et al.; A gas chromatographic-mass spectrometric (GC-MS) method using single ion monitoring (SIM) is described for the determination of residual macrolide antibiotics, oleandomycin, kitasamycin, spiramycin and tylosin, in beef and pork . For GC-MS determination, oleandomycin is acid hydrolysed to desoleandomycin and acetylated, in the same way as erythromycin . However, for elution from a GC column, the carbon-carbon double bonds in the antibiotics must be hydrogenated to single bonds before acid hydrolysis . Kitasamycin and spiramycin are therefore converted into hydroforocidine acetate and tylosin into hydro-O-mycaminosyl tylonolide acetate, which are determined by GC-MS with SIM. Biochim Biophys Acta, 1987 Mar 19, 923(3), 362 - 70 Minor modifications to the structure of tunicamycin lead to loss of the biological activity of the antibiotic; Hashim OH et al.; Three analogues of tunicamycin, each with minor alterations in structure in different regions of the molecule, have been employed to study the effects of such modifications upon the biological activity of the antibiotic . The data indicate that any modification of structure results in loss of the ability of the antibiotic to inhibit N-glycosylation of proteins . In contrast to tunicamycin itself, none of the analogues had any deleterious effects upon cellular macromolecule synthesis, nor upon the kinetics of export of de novo synthesised IgM or IgG molecules from treated rat hybridoma cells . In addition, the incorporation of tritiated sugars into acid-precipitable macromolecules was not inhibited . Endoglycosidase H digestion of isolated IgG molecules further suggested that the analogues employed did not interfere with qualitative glycosylation at the level of N-acetylglucosamine transferases I and II in the golgi apparatus . The data are consistent with the interpretation that tunicamycin has very precise structural requirements for expression of inhibitory effects upon protein glycosylation, and that small variations of structure can lead to loss of its inhibitory effects. Cancer Res, 1987 Mar 15, 47(6), 1516 - 22 Antitumor activity of a novel antitumor antibiotic, quinocarmycin citrate (KW2152); Fujimoto K et al.; A novel antitumor antibiotic, 2a,3,4,5,6,6a,7,11b-octahydro-11-methoxy-12-methyl-3,6-imino-1H-2-oxa-11 c- azanaphth(1,2,3-cd)azulene-5-carboxylic acid monocitrate (quinocarmycin citrate; KW2152) was selected for investigation in a number of experimental tumor systems because of its efficacy against P388 leukemia . In the initial studies with P388 leukemia (i.p.-i.p.), KW2152 gave an increase in life span of greater than 80% . The activity was schedule dependent and daily administration was the most effective . KW2152 caused marginal activity against L1210 leukemia, B16 melanoma, and M5076 sarcoma . The effect on cultured cells suggested that KW2152 was not cross-resistant to Adriamycin (ADM) but was cross-resistant to mitomycin C (MMC); however, KW2152 caused prolongation of life span against mice bearing P388/ADM or P388/MMC . In tests against human tumors xenografted s.c . in nude mice, KW2152 significantly inhibited the growth of MX-1 mammary carcinoma with all tumors cured at i.v . doses of 4.4 mg/kg/day and p.o . doses of 26.2 mg/kg/day given daily for 7 days . KW2152 also inhibited distinct human gastric carcinomas, St-4 and St-15 tumors, and colon carcinoma Co-3 by daily administration for 7 days . Against St-4, KW2152 gave a treated versus control percentage of 27, compared to 52 for cis-diamminedichloroplatinum . Against Co-3, KW2152 was at least as effective as MMC, ADM, cis-diamminedichloroplatinum, and bleomycin, giving a treated versus control percentage of 18 at a dose of 8.6 mg/kg/day given daily for 7 days . KW2152 showed growth inhibitory activity against cultured murine tumors and human cells . The order of in vitro efficacy of KW2152 against murine tumors, P388 leukemia greater than L1210 leukemia, B16 melanoma, correlated with the order of the sensitivity on the i.p.-i.p . systems of these tumors . The 50% inhibitory concentrations against P388 leukemia cells were 5.3 X 10(-6) and 1.1 X 10(-7) M after 1 and 72 h exposure, respectively . KW2152 caused significant inhibition of RNA synthesis after a short time exposure . In P388 leukemia cells exposed for 1 h with KW2152, the 50% inhibitory concentration for RNA synthesis was 10(-5) M, 30-fold less than that for DNA synthesis . White blood cell depression or platelet depression was not significant after administration of the i.v . 10% lethal dose given daily for 7 days . Because of its good activity against human mammary tumor MX-1 and some effectiveness against other gastric and colon carcinomas and its water solubility, a novel antitumor antibiotic, KW2152, is being developed as a Phase I anticancer agent. J Chromatogr, 1987 Mar 13, 389(2), 417 - 26 Improvement of chemical analysis of antibiotics . IX . A simple method for residual tetracyclines analysis in honey using a tandem cartridge clean-up system; Oka H et al.; A simple, rapid and precise analytical method for the residual tetracyclines in honey has been established using a tandem cartridge clean-up system (prepacked reversed-phase and ion-exchange cartridges) followed by high-performance liquid chromatography . The recoveries of oxytetracycline (OTC), tetracycline (TC), chlortetracycline (CTC) and doxycycline (DC) from honey spiked at a level of 1.0 ppm are 87.1, 85.3, 98.0 and 99.0%, respectively, with coefficients of variation of 1.1-3.9% . The detection limits in honey are 0.02 ppm for OTC and TC, and 0.05 ppm for CTC and DC, respectively . The time required for the analysis of four samples is only 1 h. J Chromatogr, 1987 Mar 13, 389(2), 389 - 95 High-efficiency preparative-scale reversed-phase high-performance liquid chromatographic purification of 14C-labelled antibiotics; Morecombe DJ; The 14C-labelled antibiotics {2-14C}mupirocin, and {thienyl-3-14C}temocillin cannot be satisfactorily purified on a small scale by conventional methods of chromatography or recrystallisation . Their purification was successfully achieved by high-efficiency preparative-scale reversed-phase high-performance liquid chromatography . The purifications employed 250 mm X 10 mm I.D . or 22 mm I.D . stainless-steel columns packed with Merck LiChrosorb RP-18 (10 microns) stationary phase which were eluted with aqueous buffer solutions at flow-rates of 10-25 ml min-1 using conventional analytical instrumentation. J Med Chem, 1987 Mar, 30(3), 481 - 6 Nucleic acid related compounds . 51 . Synthesis and biological properties of sugar-modified analogues of the nucleoside antibiotics tubercidin, toyocamycin, sangivamycin, and formycin; De Clercq E et al.; Treatment of 7-amino-3-beta-D-ribofuranosylpyrazolo{4,3-d}pyrimidine (formycin) with alpha-acetoxyisobutyryl bromide followed by deprotection of the resulting trans-vicinal acetoxy bromides and hydrogenolysis of the separated bromohydrins gave 2'-deoxy-(23%) and 3'-deoxyformycin (32%) after complete deprotection and purification of their hydrochloride salts . An analogous sequence gave 3'-deoxytoyocamycin and/or 3'-deoxysangivamycin in approximately 80% yields from toyocamycin . Antiviral, antineoplastic, and antimetabolic effects were evaluated for the formycin compounds and 4-amino-7-beta-D-ribofuranosylpyrrolo{2,3-d}pyrimidine (tubercidin), its 5-cyano- (toyocamycin), and 5-carbamoyl-(sangivamycin) antibiotic congeners in comparison with their 2'-deoxy, 3'-deoxy, and arabino analogues . In all cases, the modified-sugar compounds were less cytotoxic than the parent antibiotics . The majority also exhibited lower antiviral potency . However, the xylo-tubercidin analogue retained potent antiherpes 1 and 2 activity with decreased cytotoxicity . Labeled metabolite studies suggested that effects of these compounds on RNA and/or protein synthesis might be more significant than interference with DNA synthesis. Jpn J Antibiot, 1987 Mar, 40(3), 680 - 4 {Cefuzonam, a new cephem antibiotic in the field of pediatrics . Concentrations in serum and clinical efficacy}; Ogura H et al.; A new cephem antibiotic, cefuzonam (L-105, CZON) was studied for its concentrations in serum and clinical efficacy in the field of pediatrics . To examine the concentration of CZON in serum, 20 mg/kg of CZON was administered by intravenous drip infusion to a male patient of 6 years and 7 months . The half-life of the drug in serum was 0.97 hour after administration . CZON was administered to 7 cases of pediatric infections, and clinical result were "excellent" in 4, "good" in 1, "poor" in 2: the efficacy rate was 71.4% or 5 cases out of 7 . As an adverse reaction, eruption was observed in 1 patient. Zh Mikrobiol Epidemiol Immunobiol, 1987 Mar, (3), 110 - 8 {Detection in an experiment of a previously unknown phenomenon of the malignant transformation of bacteria as affected by antibiotics or phenol}; Sysoeva LA; The experimental study of bacteria exposed to antibiotics or phenol has revealed the hitherto unknown process of their malignant transformation . These facts are of universal importance for life sciences, as they bring about changes in the knowledge of the main processes in the life and development of organisms . The discovery of this phenomenon will help in achieving the correct solutions of cardinal problems in biology and medicine. J Vet Pharmacol Ther, 1987 Mar, 10(1), 37 - 42 The release of insoluble antibiotics from collagen ocular inserts in vitro and their insertion into the conjunctival sac of cattle; Punch PI et al.; The release rate of procaine penicillin, erythromycin and erythromycin estolate from soluble and insoluble collagen films was investigated in vitro to develop an ocular insert for the treatment of infectious bovine keratoconjunctivitis . The release rate and duration of release varied according to the selection of antibiotic and vehicle . The combination of erythromycin estolate and soluble collagen produced the most sustained drug-delivery system . However, due to the inappropriate physical properties of collagen and poor retention of ocular inserts, it was considered that the development of an antibiotic-impregnated collagen ocular insert requires further investigation. Biofizika, 1987 Mar-Apr, 32(2), 237 - 41 {Calculation of the structure of the serotonin-antibiotic lasalocid A complex by conformation analysis and the Monte Carlo method}; Alieva IN et al.; The conformational aspects of interaction of the antibiotic X537A at complexation with serotonin, hydration of molecules and their complex were studied by the methods of theoretical conformational analysis and Monte-Carlo. Acta Otolaryngol, 1987 Mar-Apr, 103(3-4), 291 - 8 The effect of aminoglycoside antibiotics on the lateral line organ of Aplocheilus lineatus (Cyprinodontidae); Kaus S; The effect of neomycin and streptomycin on the lateral line system of fishes was studied behaviourally by testing the animal's ability to localize a wave source . Increasing doses of both substances produce increasing loss of lateral line reactions, up to total inexcitability . The toxicity of both antibiotics was very similar . Lateral line sensitivity recovered 1-3 days after antibiotic removal. J Antibiot (Tokyo), 1987 Mar, 40(3), 340 - 7 Biosynthesis of the antibiotic actinorhodin . Analysis of blocked mutants of Streptomyces coelicolor; Cole SP et al.; From two types of class V act mutants of Streptomyces coelicolor two monomeric precursors of actinorhodin have been isolated and their structures determined . One is the known antibiotic kalafungin and the other a new compound . Their relationship to actinorhodin biosynthesis is discussed. J Antibiot (Tokyo), 1987 Mar, 40(3), 309 - 19 Ester-imine condensations: preparation of racemic intermediates for the synthesis of the carbapenem antibiotics PS-5 and PS-6; Ha DC et al.; The lithium enolates of ethyl butyrate and ethyl isovalerate react with N-p-methoxyphenylcinnamaldimine in tetrahydrofuran (THF)-hexamethylphosphoric triamide (HMPA) to afford predominantly trans beta-lactams 9 (67%) and 20 (78%), respectively . beta-Lactam 9 was converted to PS-5 intermediate 18 in 21% overall yield (8 steps) . Beta-lactam 20 was converted to PS-6 analog 28 in 22% overall yield using an eight step sequence. J Antibiot (Tokyo), 1987 Mar, 40(3), 290 - 5 WF-3405, a novel antitumor antibiotic . Taxonomy, isolation, structure elucidation and biological properties; Kiyoto S et al.; A new antitumor antibiotic, WF-3405 was isolated from the culture of Amauroascus aureus F-3405 . The structure has been determined as 1,5-dioxiranyl-1,2,3,4,5-pentanepentanol on the basis of spectroscopic and chemical evidence . WF-3405 exhibits strong inhibitory activity against various murine tumors including leukemia P388, leukemia L1210 and Lewis lung carcinoma. J Antibiot (Tokyo), 1987 Mar, 40(3), 281 - 9 Mulundocandin, a new lipopeptide antibiotic . II . Structure elucidation; Mukhopadhyay T et al.; The structure of a new antifungal antibiotic, mulundocandin, C48H77N7O16, was elucidated by high field NMR experiments e.g., homo- and heteronuclear correlation spectra, distortionless enhancement by polarization transfer (DEPT) spectra as well as nuclear Overhauser effect . The compound is a lipopeptide antibiotic belonging to the echinocandin class. Br Poult Sci, 1987 Mar, 28(1), 47 - 55 Interaction of dietary antibiotic supplementation and stocking density on broiler chick performance and immune response; Dafwang II et al.; The growth depression caused by reducing the space allowance in battery brooders from 0.047 to 0.019 m2 per chick was ameliorated by subtherapeutic inclusion rates of dietary antibiotics . However, the interaction of antibiotic supplementation and stocking density was not significant for the variables measured . Increasing stocking density improved the efficiency of food utilisation . The high density regimen resulted in decreased weights of the bursa and thymus relative to body weight but there was no concurrent reductions in antibody response, spleen weight or mortality. Gan To Kagaku Ryoho, 1987 Mar, 14(3 Pt 2), 845 - 9 {Spergualin, a new antitumor antibiotic}; Takeuchi T; Spergualin is a new antitumor antibiotic which has a very unique structure . It was shown to have chemotherapeutic effects on mice inoculated with various mouse leukemias such as L-1210 (IMC), L-1210, P388, P815, C1489, EL4 and RL male 1 . Among these, spergualin was especially effective against L-1210 (IMC) tumors, where the mice were completely cured at an appropriate drug dosage . These cured mice rejected the second challenge of L-1210, but not other tumors, indicating that specific immunity had been induced by spergualin . Preliminary data suggested that killer T cells were acting as effector cells . There was some correlation between the cytocidal activity of spergualin and the concentrations of amine oxidases in the serum . These results suggest that the induction of tumor-immunity plays an important role in the antitumor activity of spergualin. J Trauma, 1987 Mar, 27(3), 250 - 5 Penetrating abdominal trauma: the use of operative findings to determine length of antibiotic therapy; Rowlands BJ et al.; Penetrating abdominal trauma is associated with a high incidence of postinjury infection which can be reduced by appropriate surgical management and short-term antibiotic therapy . Patients at high risk for developing infectious complications may be identified on the basis of operative findings and the duration of the postinjury antibiotic regimen determined . Colonic injury is the most important determinant of infectious complications . Number of other organs injured, age, and mode of injury have little or no additional impact on infection rates . Low-risk patients can be successfully managed with three perioperative doses of antibiotics . Nontrauma related nosocomial infections appear to be associated with trauma related infections in high-risk patients . Intravenous clindamycin plus tobramycin and metronidazole plus tobramycin for 72 hours postinjury are equally effective in reducing postinjury infections in "high-risk" patients. J Bacteriol, 1987 Mar, 169(3), 1321 - 4 Tn5 insertion in the polynucleotide phosphorylase (pnp) gene in Escherichia coli increases susceptibility to antibiotics; McMurry LM et al.; A Tn5 insertional mutation on the Escherichia coli chromosome which caused a severalfold increase in susceptibility to structurally and functionally diverse antibiotics was found to map within the gene for polynucleotide phosphorylase (pnp) and to inactivate this enzyme, which is involved in RNA breakdown . The mutation also decreased the growth rate 10 to 25% and increased the rate of tetracycline uptake about 30% . The hypersensitivity due to the insertion was only partially complemented by a cloned pnp gene. Biochim Biophys Acta, 1987 Feb 26, 897(2), 229 - 37 Temperature-dependent modes for the binding of the polyene antibiotic amphotericin B to human erythrocyte membranes . A circular dichroism study; Szponarski W et al.; The interaction of amphotericin B with isolated human erythrocyte ghosts was monitored by circular dichroism at 37 degrees C and 15 degrees C . Although different, these spectra were not concentration dependent over a concentration range covering the inducement of K+ leakage and hemolysis, which suggests the existence of only one bound amphotericin B species . At 15 degrees C, the spectra indicate that amphotericin B is complexed with membrane cholesterol; the complex formation is saturable but not cooperative . At 37 degrees C new spectra are observed, and their existence is conditioned by the presence of membrane proteins . The binding is cooperative but not saturable . The amphotericin B right side-out vesicles complexation is temperature as well as ionic strength dependent: at high ionic strength it is the same as with ghosts, with the same temperature dependence . At low ionic strength it is characteristic of an interaction with cholesterol, regardless of temperature . In the large unilamellar vesicles reconstituted from the total lipid extracts of erythrocyte membranes, amphotericin B is complexed with cholesterol, regardless of temperature and ionic strength . These results indicate that there are two different modes of amphotericin B complexation with erythrocyte membranes, reversible one in the other, depending on the molecular organization of the membrane and the presence of membrane proteins. Biochemistry, 1987 Feb 24, 26(4), 1152 - 63 Interactions between an anthracycline antibiotic and DNA: molecular structure of daunomycin complexed to d(CpGpTpApCpG) at 1.2-A resolution; Wang AH et al.; The crystal structure of a daunomycin-d(CGTACG) complex has been solved by X-ray diffraction analysis and refined to a final R factor of 0.175 at 1.2-A resolution . The crystals are in a tetragonal crystal system with space group P4(1)2(1)2 and cell dimensions of a = b = 27.86 A and c = 52.72 A . The self-complementary DNA forms a six base pair right-handed double helix with two daunomycin molecules intercalated in the d(CpG) sequences at either end of the helix . Daunomycin in the complex has a conformation different from that of daunomycin alone . The daunomycin aglycon chromophore is oriented at right angles to the long dimension of the DNA base pairs, and the cyclohexene ring A rests in the minor groove of the double helix . Substituents on this ring have hydrogen-bonding interactions to the base pairs above and below the intercalation site . O9 hydroxyl group of the daunomycin forms two hydrogen bonds with N3 and N2 of an adjacent guanine base . Two bridging water molecules between the drug and DNA stabilize the complex in the minor groove . In the major groove, a hydrated sodium ion is coordinated to N7 of the terminal guanine and the O4 and O5 of daunomycin with a distorted octahedral geometry . The amino sugar lies in the minor groove without bonding to the DNA . The DNA double helix is distorted with an asymmetrical rearrangement of the backbone conformation surrounding the intercalator drug . The sugar puckers are C1,C2'-endo, G2,C1'-endo, C11,C1'-endo, and G12,C3'-exo . Only the C1 residue has a normal anti-glycosyl torsion angle (chi = -154 degrees), while the other three residues are all in the high anti range (average chi = -86 degrees) . This structure allows us to identify three principal functional components of anthracycline antibiotics: the intercalator (rings B-D), the anchoring functions associated with ring A, and the amino sugar . The structure-function relationships of daunomycin binding to DNA as well as other related anticancer drugs are discussed. Cancer Res, 1987 Feb 15, 47(4), 1036 - 9 Loss of fluorescence by anthracycline antibiotics: effects of xanthine oxidase and identification of the nonfluorescent metabolites; Dodion P et al.; Rat liver cytosol and buttermilk xanthine oxidase both converted 7-deoxypyrromycinone, the 7-deoxyaglycone of marcellomycin, a new anthracycline antibiotic, to a nonfluorescent compound under anaerobic conditions and in the presence of an electron donor . Reduced nicotinamide adenine dinucleotide and reduced nicotinamide adenine dinucleotide phosphate were equally effective electron donors for liver cytosol, and xanthine was the best cofactor for xanthine oxidase . However, xanthine was inactive with liver cytosol . Reactions with xanthine oxidase obeyed Menten-Michaelis kinetics and were inhibited by allopurinol . No xanthine oxidase activity was detected in liver cytosol . Xanthine oxidase also induced a loss of fluorescence when incubated with 7-deoxydaunorubicin aglycone . The nonfluorescent metabolite of 7-deoxypyrromycinone was tentatively identified as the dihydroquinonic derivative of the parent deoxyaglycone on the basis of its spectrophotometric, fluorescent, thin layer chromatographic, and mass spectral characteristics . Our data demonstrate that more than one enzymatic activity, xanthine oxidase, and an unidentified rat liver cytosolic enzyme convert the 7-deoxyaglycones of anthracycline antibiotics to nonfluorescent metabolites. Nature, 1987 Feb 26-Mar 4, 325(6107), 818 - 21 Homology between Streptomyces genes coding for synthesis of different polyketides used to clone antibiotic biosynthetic genes; Malpartida F et al.; Many important antibiotics such as tetracyclines, erythromycin, adriamycin, monensin, rifamycin and avermectins are polyketides . In their biosynthesis, multifunctional synthases catalyse iterated condensation of thio-esters derived from acetate, propionate or butyrate to yield aliphatic chains of varying length and carrying different alkyl substituents . Subsequent modifications, including aromatic or macrolide ring closure or specific methylations or glycosylations, generate further chemical diversity . It has been suggested that, if different polyketide synthases had a common evolutionary origin, cloned DNA coding for one synthase might be used as a hybridization probe for the isolation of others . We show here that this is indeed possible . Study of a range of such synthase genes and their products should help to elucidate what determines the choice and order of condensation of different residues in polyketide assembly, and might yield, by in vitro recombination or mutagenesis, synthase genes capable of producing novel antibiotics . Moreover, because genes for entire antibiotic pathways are usually clustered in Streptomyces, cloned polyketide synthase genes are valuable in giving access to groups of linked biosynthetic genes. Jpn J Antibiot, 1987 Feb, 40(2), 284 - 94 {The trend of childhood bacterial meningitis in Japan (1979-1984) . Part 3 . On the antibiotic therapy and prognosis}; Fujii R et al.; We studied 973 cases of childhood bacterial meningitis from 1979 through 1984 by means of questionnaire . Monotherapy was carried out in 47.9% of patients with case mortality of 10.3%, whereas those treated with 2 and 3 antibiotics revealed higher rates of 15.8% and 13.5%, respectively . Penicillins (PCs) were the most frequently used for monotherapy, and ampicillin (ABPC) accounted for 48.7%, then followed by cephalosporins (CEPs) group V including latamoxef (LMOX) for 26.8%, with fatality rates of 11.0% for the former and 9.6% for the latter . Chloramphenicol (CP) was used in 19 cases, 4 cases were treated with antibiotics other than PCs, CEPs, CP and aminoglycosides (AGs), and no death resulted . Among 418 cases treated with 2 different antibiotics, 241 cases with aminoglycosides (AGs) revealed a case mortality of 22.4%, and remaining 177 cases where AGs was not used showed a rate of 6.8% (P less than 0.05) . One hundred and thirty-one cases treated with ABPC with gentamicin gave 29 deaths showing a significantly high mortality of 22.1% . Similar results were obtained for those treated with ABPC with other AGs . Combination of one PCs with another PCs and PCs with CEPs resulted in lower mortalities of 12.5% and 6.1%, respectively and the combination of beta-lactam with non-AGs antibiotics revealed only 4 deaths out of 74 cases, i.e., a case mortality of 5.4% . A gradual decrease of single or combined use of ABPC, mainly with AGs was observed during the survey period and a rapid increase of CEPs V and LMOX therapy occurred after 1982. Zentralbl Bakteriol Mikrobiol Hyg {A}, 1987 Feb, 263(3), 377 - 88 Antibiotic therapy in early erythema migrans disease and related disorders; Weber K et al.; Between December 1978 and July 1985, we used various antibiotics for the treatment of 97 adult patients with early erythema migrans disease (EMD) . Six patients with borrelial lymphocytoma (BL) and 20 with acrodermatitis chronica atrophicans (ACA) were treated similarly . Follow-up was for a median of 20, 14, and 12 months, respectively . The erythema migrans and all associated symptoms resolved within a median of 3 weeks (0.5-18.4), BL within 7 weeks (4-16), and ACA partly or completely within several months . A Jarisch-Herxheimer (-like) reaction was observed in 8 patients with EMD . Fourteen patients with EMD and one with ACA developed an exacerbation of symptoms or new manifestations between the 2nd and 20th day, and 28 patients with EMD and one with ACA continued to have or acquired various symptoms greater than or equal to 3 weeks after initiation of therapy . Arthralgia, neurologic and constitutional symptoms, and in one instance a slight pulmonary interstitial edema developed in EMD . More severe initial illness was a risk factor for the development of later symptoms in EMD . Retreatment was more often necessary in ACA than in EMD . A patient with ACA had a recurrence after 5 1/2 years . IgG antibody titers rose at least fourfold in 5 patients with ACA and in 1 with EMD despite therapy . We tentatively recommend minocycline or high doses of parenteral penicillin for the treatment of these disorders. J Hand Surg {Br}, 1987 Feb, 12(1), 123 - 4 Antibiotics in open fractures of the distal phalanx? Sloan JP, Dove AF, Maheson M, Cope AN, Welsh KR. A prospective trial was undertaken on 85 adult patients with open fractures of the distal phalanges of less than 6 hours duration, treated by conventional surgery . They either received no antibiotic therapy, or cephradine in short or long courses . The infection rate was 30% in the group without antibiotics and less than 3% in the treated groups . Three different antibiotics regimes were compared, with no difference in the infection rate: therefore the simplest and surest method, a single pre-operative dose and a single post-operative dose, is recommended. J Antibiot (Tokyo), 1987 Feb, 40(2), 202 - 8 Macrophage-specific effect on lipid metabolism by an antibiotic, ascofuranone; Magae J et al.; Ascofuranone (AF) enhanced glucose consumption of splenocytes and macrophages, while it enhanced incorporation of {14C}acetate into macrophages but not into splenocytes . When using tumor cell lines, it inhibited the incorporation of {14C}acetate into lymphoma cell lines, YAC-1 and P388, and a thymoma, L5178Y, while it stimulated that into P388D1, which is derived from P388 and has macrophage-like characteristics . Incorporation of {14C}acetate into a mammary carcinoma FM3A was also stimulated by AF . In contrast, AF stimulated uptake of methylglucose in all cell lines tested . The effect of AF was further studied using mouse myeloid leukemia, M1 cells . AF slightly stimulated the incorporation of {14C}acetate into undifferentiated M1 cells, and strongly stimulated that of hydrocortisone-differentiated M1 cells . In contrast, AF suppressed the incorporation of {14C}acetate into retinoic acid-differentiated M1 cells . Glucose consumption of these three types of M1 cells was all stimulated . From these results, we conclude that AF specifically stimulates the incorporation of {14C}acetate into macrophages while it generally stimulates glucose uptake of the cells. J Antibiot (Tokyo), 1987 Feb, 40(2), 195 - 201 Enzymatic phosphorylation of macrolide antibiotics; Wiley PF et al.; Five macrolide antibiotics (erythromycin A, 1; oleandomycin, 3a; tylosin, 4a; spiramycins, 5a; leucomycin A3, 6a) have been phosphorylated enzymatically using cell-free extracts derived from Streptomyces coelicolor UC 5240 . The necessary cofactors and the rates of the conversion have been determined. Appl Environ Microbiol, 1987 Feb, 53(2), 331 - 6 Subtherapeutic levels of antibiotics in poultry feeds and their effects on weight gain, feed efficiency, and bacterial cholyltaurine hydrolase activity; Feighner SD et al.; A radiochemical method was developed to estimate cholyltaurine hydrolase potentials and rates of cholyltaurine hydrolysis in chicken intestinal homogenates . This method was used to monitor the effects of antibiotic feed additives on cholyltaurine hydrolase activity . Avoparcin, bacitracin methylenedisalisylic acid, efrotomycin, lincomycin, penicillin G procaine, and virginiamycin improved rate of weight gain and feed conversion of chicks and decreased cholyltaurine hydrolase activity in ileal homogenates relative to those of nonmedicated control birds . The results provided the first evidence that feeding selected antibiotics at subtherapeutic levels can affect bile acid-transforming enzymes in small-intestinal homogenates . The inverse relationship between growth performance and cholyltaurine hydrolase activity raises the possibility that specific inhibitors of this enzyme may promote weight gain and feed conversion in livestock and thereby reduce or eliminate the need for antibiotic feed additives. J Med Chem, 1987 Feb, 30(2), 333 - 40 Comparison of aminoglycoside antibiotics with respect to uptake and lethal activity in Escherichia coli; Allen NE et al.; Forty-five aminoglycoside antibiotics and related compounds were compared for their ability to induce the accumulation of dihydrostreptomycin in Escherichia coli K12 . The common aminoglycosides and a streptothricin antibiotic all induced enhanced uptake within a relatively narrow concentration range . These concentrations were lethal to the bacteria . Comparison of aminoacyl derivatives of tobramycin and apramycin, the latter synthesized utilizing transition-metal cations to selectively control the site of substitution, revealed that 1-N-aminoacyl modifications resulted in an increased ability to induce enhanced uptake . 2'-N-Aminoacyl modifications were also effective at inducing enhanced uptake, albeit without noticeable improvement over parent . The findings from this structure-activity comparison support the proposition that aminoglycosides share a common critical target (most likely the ribosome), which, when acted upon, results in both drug accumulation and killing. Biomed Environ Mass Spectrom, 1987 Feb, 14(2), 91 - 6 Redox reactions occurring during secondary ion mass spectrometry of some heteroanthracycline antitumor antibiotic precursors; Main DE et al.; Positive and negative secondary ion mass spectra of the title compounds were produced by bombardment of solid deposits by 13 and 23 KeV cesium ions, respectively, and analyzed with a time-of-flight mass spectrometer . In addition to familiar protonation and alkali (mainly sodium) ion addition processes observed in the positive ion spectra and proton abstractions in the negative ion spectra (which enable determination of molecular weight) there is evidence from both spectral modes for oxidation-reduction processes in which species such as {M - H}+, {M - H + Na}+ . and {M + 1}- are formed . It is argued that these may be formed rapidly from pre-associated molecules during bombardment/ionization rather than as a result of radiation damage . Sodium ion addition is apparently facilitated by the presence of electron pair donor groups, especially if chelation is possible. J Chromatogr, 1987 Jan 16, 386, 325 - 32 Preparative low-pressure chromatography of antibiotics on a column of diol-bonded silica gel; Rasmussen RR et al.; Several schemes are presented which illustrate the general utility of column chromatography on diol-bonded silica gel for the purification of various antibiotics . The antibiotics include rosarimicin, rosarimicin dimethylacetal, everninomicin D, Juvenimicin A4, coloradocin and the benzanthrins . A set of partition coefficients, determined in different two-phase solvent systems, for a given antibiotic or antibiotic complex, can be used in selecting appropriate solvent systems for this chromatography as well as for semi-preparative counter-current chromatography on the Ito coil planet centrifuge. J Chromatogr, 1987 Jan 16, 386, 229 - 41 Separation of amino acids and antibiotics by narrow-bore and normal-bore high-performance liquid chromatography with pre-column derivatization; Fiedler HP et al.; The selectivity, efficiency and lifetime of normal- and narrow-bore columns for high-performance liquid chromatography were investigated for the separation and quantification of amino acids and the amino acid-like antibiotics phosphinothricin and phosphinothricylalanylalanine in biological samples . These compounds were determined by an automated pre-column derivatization with o-phthalaldehyde-2-mercaptoethanol reagent and UV detection at 338 nm. Cancer Res, 1987 Jan 1, 47(1), 96 - 9 Suppression of hypertriglyceridemia of Ehrlich carcinoma-bearing mice by an antibiotic, ascofuranone; Magae J et al.; Ehrlich ascites carcinoma-bearing mice exhibit hypertriglyceridemia . An antitumor antibiotic, ascofuranone, suppressed tumor-induced hypertriglyceridemia when administered i.p . even when no evident antitumor activity was observed without affecting the levels of free fatty acids, phospholipids, cholesterol, glucose, and total protein in plasma . Ascofuranone did not reduce plasma triglycerides of normal mice . Insulin and clofibrate, known modifiers of lipid metabolism, showed no significant suppression . Ascofuranone is also effective on solid tumor-induced hypertriglyceridemia . Another notable change of metabolism affected by tumor-bearing in the early stage where hypertriglyceridemia has not yet fully progressed is hypoglycemia . Although ascofuranone did not affect hypoglycemia, the suppressive effect on hypertriglyceridemia was more evident when ascofuranone was administered in the early stage than in the later stage . These results suggest that ascofuranone suppresses hypertriglyceridemia by specifically affecting the changes of host metabolism which is induced in the early stage of tumor bearing. Chem Biol Interact, 1987, 64(1-2), 61 - 70 Association of polyene antibiotics with sterols; Kito M et al.; Molecular interaction between amphotericin B and sterols in non-aqueous solutions was examined quantitatively by spectroscopic methods in order to support the view point that selectivity of amphotericin B is more pronounced in the presence of ergosterol than of cholesterol . The most likely association complexes between ergosterol and amphotericin B are 4:1, 6:1 stoichiometric complex when the concentrations of amphotericin B are 3.93 x 10(-4) M, 1.94 x 10(-4) M respectively . The presence of 3 beta-OH group is necessary but not enough for the association with amphotericin B . It appears that the extent of spectral change of amphotericin B induced by complexing sterol is greater for ergosterol than cholesterol. J Hyg Epidemiol Microbiol Immunol, 1987, 31(3), 269 - 78 Resistance to antibiotics in humans and animals on the Cape Verde Islands; Buchrieser C et al.; From the Cape Verde Islands no studies are known about an efficient treatment with antibiotics and chemotherapeutics . Because of this human samples and samples of domestic animals were collected, the different bacterias were isolated and the antibiograms were analyzed by agar-diffusions-test . The human samples consisted of wound-, eye-, anal-, vaginal- and throat-smears, the animal samples consisted of jaw-, anal- and wound-smears . the aim of these investigations was to make efficient treatment with antibiotics and chemotherapeutics possible . The best efficacy had Cefotaxim, Gentamicin and Trimethoprim + Sulfonamid . Very poor were Penicillin G, Aminopenicillin and Cephalexin. Adv Enzyme Regul, 1987, 26, 301 - 16 Biochemical pharmacology and experimental chemotherapy studies with guanine-7-oxide, a novel purine antibiotic; Jackson RC et al.; 1 . Guanine-7-oxide is a novel purine antibiotic produced by a Streptomyces species, ATCC 39364 . 2 . Guanine-7-oxide is cytotoxic to murine and human leukemia cells in vitro at sub-micromolar concentrations . Murine and human carcinoma cells are much less sensitive . 3 . Guanine-7-oxide has significant in vivo antitumor activity, particularly against the intraperitoneal and subcutaneous L1210 leukemia systems . 4 . Guanine-7-oxide, at highly cytotoxic concentrations, has little effect on biosynthesis of RNA and DNA . 5 . There is preliminary evidence for an early effect of guanine-7-oxide on cellular protein synthesis . 6 . Guanine, guanosine and hypoxanthine protect cells from the cytotoxicity of guanine-7-oxide . 7 . Activation of guanine-7-oxide requires the presence of the enzyme hypoxanthine-guanine phosphoribosyltransferase in the target cells . 8 . Cytotoxic concentrations of guanine-7-oxide do not cause depletion of cellular guanine nucleotides during a two hr incubation period . 9 . Guanine-7-oxide is converted within mouse and human cells to a metabolite with chromatographic mobility corresponding to a ribonucleoside 5'-triphosphate. Drugs Exp Clin Res, 1987, 13(4), 233 - 6 Aminoglycoside antibiotics: interaction with trimethaphan at the neuromuscular junctions; Paradelis AG et al.; Trimethaphan, a ganglionic blocking agent which is administered by intravenous drip to produce controlled hypotension during surgery, produces a complete neuromuscular blockade at the isolated phrenic nerve-hemidiaphragm preparation of the rat at a concentration of 0.3 mmol X l-1 . This blockade is not reversed by neostigmine, a cholinesterase inhibitor, nor by calcium chloride, and this action is attributed to the local anaesthetic activity of the drug . Trimethaphan (1.5 X 10(-2) mmol X l-1) interacts with the following aminoglycoside antibiotics: gentamicin (0.04), streptomycin (0.05), netilmicin (0.06), amikacin (0.11), sisomicin (0.14), kanamycin (0.17), tobramycin (0.18) and dibekacin (0.21 mmol X l-1) to produce a complete neuromuscular blockade . These pharmacodynamic interactions of trimethaphan and aminoglycoside antibiotics occur at significantly reduced concentrations of the interacting drugs which are very close to the ones obtained after administration of therapeutic doses . When trimethaphan or aminoglycoside antibiotics are used alone at the above reduced concentrations they do not exert any neuromuscular blocking activity . The neuromuscular blockade which is obtained after the interaction of trimethaphan with aminoglycoside antibiotics is not reversed by either neostigmine or calcium chloride, although the neuromuscular blockade which is produced by aminoglycoside antibiotics alone is reversed by calcium chloride . It is concluded that the local anaesthetic effect of trimethaphan is the predominant factor of the mechanism of the above interactions . These interactions may produce severe respiratory disturbances (respiratory depression or apnoea) to the patients, during the perioperative period, which can be reversed only with artificial ventilation. Cancer Chemother Pharmacol, 1987, 20(1), 33 - 6 Dose-dependent skin ulcers in mice treated with DNA binding antitumor antibiotics; Soble MJ et al.; The DNA-binding agents daunomycin (DAU-NO), mithramycin (MITH), dactinomycin (ACT-D), amsacrine (mAMSA) and esorubicin (ESO) were tested for local vesicant potential in a quantitative intradermal mouse skin model . Only MITH, which adlineates but doses not intercalate DNA, did not produce dose-dependent skin ulcerations in the mouse . The anthracycline antibiotics DAUNO and ESO produced the largest skin ulcers when administered intradermally at clinically relevant doses (adjusted on the basis of comparable body surface areas) . Numerous local pharmacologic adjuvants were tested for activity to decrease skin ulceration patterns in mice given one of the DNA intercalators . Inactive local adjuvants included heat, cold, saline, hyaluronidase, glucorticosteroids and isoproternol . Only one adjuvant, topical dimethylsulfoxide (DMSO), was found to reduce DAUNO skin lesions . A single topical DMSO application significantly decreased ulceration size to almost half of control levels . However, it was ineffective for the other intercalating agents . These results show that the DNA intercalators DAUNO, ESO and ACT-D are potent vesicants in a mammalian skin model . These vesicant agents must be administered cautiously to prevent extravasation . No single local adjuvant treatment can be recommended for extravasation of these drugs in the clinic . One significant exception is DAUNO, where topical DMSO may reduce clinical toxicities. J Antibiot (Tokyo), 1987 Jan, 40(1), 66 - 72 Studies on macrocyclic lactone antibiotics . XI . Anti-mitotic and anti-tubulin activity of new antitumor antibiotics, rhizoxin and its homologues; Takahashi M et al.; The mode of action of rhizoxin (1a), a new antitumor macrolide, was investigated . Rhizoxin inhibited fusion of the male and the female pronuclei in fertilized sea urchin eggs and inhibited cilia formation in the deciliated sea urchin embryos . In vitro, polymerization of tubulin isolated from porcine brains was completely inhibited at a 1 X 10(-5) M concentration of rhizoxin, and tubulin which had been polymerized by incubation at 37 degrees C for 30 minutes was depolymerized by addition of 1 X 10(-5) M of the drug . Activity of rhizoxin against tubulin polymerization was compared with those of other anti-tubulin drugs such as colchicine, vinblastine and ansamitocin P-3 . The homologues of rhizoxin, 1b-3b, also inhibited polymerization of the purified microtuble protein at almost the same extent as rhizoxin. Z Exp Chir Transplant Kunstliche Organe, 1987, 20(2), 94 - 8 {Effects of a single intra-articular injection of antibiotics on cartilage structure in rabbits}; Bailleu E et al.; Nebacetin, chloramphenicol, penicillin, and isotonic sodium chloride solution were injected once into 80 knee- and elbow-joints of rabbits . The histologic investigation of the hyaline cartilage after 2 respectively 5 months did not show any kind of lesions . The results of other authors in similar investigations and the indication for intra-articular application of antibiotics are discussed. J Nat Prod, 1987 Jan-Feb, 50(1), 108 - 18 Biosynthesis of the ansamycin antibiotic ansatrienin (mycotrienin) by Streptomyces collinus; Wu TS et al.; The biosynthesis of ansatrienin (mycotrienin) has been studied in radioactive and stable isotope feeding experiments with Streptomyces collinus Tu 1892 . The m-C7N unit of the ansa ring is efficiently and specifically derived from 3-amino-5-hydroxybenzoic acid; shikimic acid is not incorporated into this part of the molecule but does label the cyclohexanecarboyxlic acid moiety, providing all seven of its carbon atoms . Incorporation of methionine confirms origin of the methoxy group by transmethylation . The D-alanine moiety is derived directly from D-alanine rather than L-alanine . The terminal steps in the conversion of shikimic acid into cyclohexanecarboyxlic acid seem to be sequential reduction of 2,5-dihydrobenzoic acid and cyclohexene-1-carboxylic acid as evidenced by feeding experiments and the detection of a new ansatrienin containing a 1-cyclohexene instead of the cyclohexane moiety. Gastrointest Radiol, 1987, 12(3), 257 - 61 CT appearance of antibiotic-induced colitis; Letourneau JG et al.; Eleven abdominal computed tomographic (CT) examinations were performed in 10 patients with antibiotic-induced colitis . The clinical, endoscopic, and CT findings are presented . The most common CT findings were colonic dilatation and bowel wall thickening . However, small bowel dilation was commonly seen . Intramural gas and ascites were less frequent findings . The diagnosis of antibiotic-induced colitis was rarely made before CT examination . Consequently, attentiveness to these CT abnormalities can expedite specific treatment . When these findings are noted on CT they represent the equivalent of toxic megacolon and administration of rectal contrast is contraindicated. Jpn J Antibiot, 1987 Jan, 40(1), 136 - 44 {The neuromuscular blocking activity of isepamicin sulfate (HAPA-B) compared with other aminoglycoside antibiotics}; Shinoda Y et al.; Effects of isepamicin sulfate (HAPA-B), a new aminoglycoside antibiotic, on the neuromuscular transmission were studied in rats and compared with those of amikacin (AMK) or other aminoglycoside antibiotics . The HAPA-B, as well as other aminoglycoside antibiotics, depressed the twitch response of diaphragm to phrenic nerve stimulation in vitro . The depression effects of different drugs were compared and graded in the order of strengths of blocking action as: netilmicin (NTL) greater than gentamicin (GM) greater than streptomycin (SM) greater than kanamycin (KM) greater than AMK greater than HAPA-B . The IC50 (concentration which inhibited the response by 50%) of HAPA-B was 3.6 X 10(-3) g/ml . The neuromuscular blockade produced by HAPA-B was reversed by CaCl2, KCl or caffeine but not by neostigmine . D-Tubocurarine or MgCl2 augmented the neuromuscular effects of HAPA-B . Intramuscular (400 mg/kg) and intravenous (100 mg/kg) injections of HAPA-B did not affect the twitch response of gastrocnemius muscle to sciatic nerve stimulation in situ . Intravenous injection of 200 mg/kg caused death in some rats and depression of the twitch response in others . Intravenous AMK produced no significant effect on the twitch response at 50 mg/kg and caused death at 100 mg/kg . GM and SM caused death or significant degree of depression of the twitch response at intravenous doses of 50 mg/kg . In experiments of intravenous drug infusion for 60 minutes, the twitch response was depressed by HAPA-B at 400 mg/kg/hr and by AMK at 200 and 400 mg/kg/hr . In conclusion, HAPA-B has a neuromuscular blocking action presumably at the nerve terminal . However, its action was the weakest among the aminoglycoside antibiotics tested. Zh Nevropatol Psikhiatr Im S S Korsakova, 1987, 87(3), 381 - 5 {Pathology of the nervous system caused by antibiotics as a manifestation of allergic vasculitis}; Gerasimova MM; The author studied the clinical picture and identified forms of neurological disorders in patients suffering from occupational diseases associated with their exposure to antibiotics . The following pathological forms were prevalent: diffuse damage to the nervous system (meningo-encephalo-myelo-polyradiculoneuritis), focal cerebral lesion, disseminated cerebral micro-symptoms, vegetovascular dystonia . It is concluded on the basis of clinical findings and data from clinical and physiological examination that neurological disturbances are an individual manifestation of systemic pathology with allergic vasculitis being the underlying cause. Jpn J Pharmacol, 1987 Jan, 43(1), 73 - 80 Studies on the nephrotoxicity of aminoglycoside antibiotics and protection from these effects (4) . Effects of tobramycin alone and in combination with latamoxef on the stability of rat kidney lysosomal membranes; Kojima R et al.; Effects of tobramycin (TOB) alone and in combination with latamoxef (LMOX) on the stability of rat kidney lysosomal membranes were investigated . Rats were injected with doses of TOB (90 mg/kg/day, s.c.) alone . LMOX (2,000 mg/kg/day, s.c.) alone or TOB (90 mg/kg/day, s.c.) and LMOX (2,000 mg/kg/day, s.c.) for 5 consecutive days . The rat kidney lysosomes were isolated on the 1st, 3rd and 5th days and incubated in a 0.25 M sucrose solution containing 1 mM EDTA (pH 7.0) at 37 degrees C for 20 min . After incubation, the activity of N-acetyl-beta-D-glucosaminidase (NAG) released from lysosomes was measured, and the percent NAG release was calculated as an index of the stability of lysosomal membranes . The percent releases of NAG from lysosomes of TOB alone-treated rats were 40 and 50% greater than those of normal rats on the 1st and 3rd days, respectively . On the other hand, treatment with TOB and LMOX suppressed the NAG release from lysosomes with TOB alone by about 80 to 100% . There were insignificant slight increases in the percent NAG release in LMOX alone-treated rats on the 3rd and 5th days . In addition, the in vitro study indicated that incubation of the lysosomal fraction from kidneys of normal rats with TOB (30 micrograms/ml) significantly increased the NAG release, compared with that of the non-treated lysosomal fraction . However, the preincubated mixture of TOB (30 micrograms/ml) and LMOX (50 micrograms/ml) in vitro significantly suppressed the release of NAG from lysosomes by 85% . These results suggest that the suppression of the releases of NAG from lysosomes by the combination of TOB with LMOX may contribute to the protective effect of LMOX against TOB nephrotoxicity. Scand J Infect Dis, 1987, 19(1), 123 - 30 Antibiotic usage in surgery in a large teaching hospital; Karlsson M et al.; A prevalence study of the antibiotic usage in the surgical departments at the Karolinska Hospital, Stockholm, showed that 126/517 hospitalized patients (24%) received antibiotics and that 100/306 operated patients (33%) received antibiotics . 44 (44%) of the operated patients were given their antibiotics as prophylaxis and 46 (37%) of all patients receiving antibiotics were given them as prophylaxis . Antibiotics were administered intravenously to 35 (28%) patients, orally to 75 (60%), and topically to 16 patients (13%) (eye department only) . The most commonly used drugs in prophylaxis were isoxazolylpenicillins and trimethoprim-sulphonamide while cephalosporins accounted for a minor part . In therapy the most commonly used drug was isoxazolylpenicillin, followed by ampicillin derivatives, metronidazole, tetracyclines, trimethoprim-sulphonamide and cephalosporins . The pattern of antibiotic usage differed markedly between departments. J Clin Chem Clin Biochem, 1987 Jan, 25(1), 49 - 52 Interference by the new antibiotic cefpirome and other cephalosporins in clinical laboratory tests, with special regard to the "Jaffé" reaction; Grotsch H et al.; The new cephalosporin, cefpirome, was investigated for its possible interference in clinical laboratory tests, especially the determination of creatinine . Tests for bilirubin, cholesterol, protein, urea, and uric acid were also studied . A selection of commercially available compounds such as cefoperazone, cefazolin, cefamandole, cefoxitin, latamoxef, ceftriaxon, cefotiam, cephaloridine, cephalotin, cefotaxime, cefazedone and cefuroxime, and cefodizime (a compound under development) were also included in these investigations . Interference was found only with the "Jaffe method" for the determination of creatinine . Pronounced interactions with alkaline picrate were observed with cefpirome, cefoxitin, cephalotin and cephaloridine, whereas the other compounds showed only weak reaction or no reaction at all . The cephalosporins did not interfere in any of the other tests mentioned above . Care must therefore be taken in the determination of creatinine in samples from patients under treatment with these drugs . The assay methods of choice at present are enzymatic or specific HPLC assays. J Basic Microbiol, 1987, 27(9), 521 - 8 An antibiotic-overproducing mutant of Streptomyces granaticolor with impaired differentiation; Stastna J et al.; A thy- tetracycline-resistant mutant of Streptomyces granaticolor was prepared by mutagenesis of the parental strain ETH 7437 . The mutant exhibits a different morphology and an overproduction of granaticins . The ability to form an aerial mycelium and spores has been lost . The mutant cells have a round or an atypical shape and a thick cell wall, the membraneous system is enlarged by numerous mesosomes . Division septa are formed rarely . The mutant is more sensitive to both low and high temperature than the parental strain . The altered features are stably maintained for many generations . Ribosomal proteins of the mutant do not differ substantially from those of the original strain indicating that the mutant phenotype is not due to an alteration at the translational level. Psychopathology, 1987, 20(3-4), 129 - 35 Psychopathology of organic mental disorders due to infections in the antibiotics era . Stability of syndromes and classification; Marneros A et al.; 104 patients diagnosed as having an organic mental disorder due to infection were classified according to DSM III criteria . The vast majority of patients (76%) fulfilled the criteria of delirium, 6% that of organic hallucinosis, while others had to be classified as affective, personality or delusional syndrome . We found a great instability of syndromes causing classification problems . A classification rule is suggested, which we called 'compromise of clinical reality'. Drugs Exp Clin Res, 1987, 13(12), 719 - 25 Dactimicin, a new, less toxic aminoglycoside antibiotic active against resistant bacteria; Omoto S et al.; Dactimicin is a new member of the pseudodisaccharide group of antibiotics . It possesses an unusual N-formimidoyl group which differentiates it from astromicin . Dactimicin is active against wide variety of bacteria, including resistant strains with aminoglycoside-modifying enzymes . However, AAC(3)-I enzyme slowly acetylates dactimicin . Animal toxicity studies show that the ototoxicity and nephrotoxicity of dactimicin are lower than those of amikacin and gentamicin . No notable abnormal findings have been found in pharmacological and toxicological studies. Cytobios, 1987, 52(210-211), 135 - 52 Protein supplements, mitogens and antibiotics in lymphoblast transformation and cytogenetic analysis; Drouin R et al.; The in vitro effects of four protein supplements, foetal calf serum (FCS), gammaglobulin-depleted FCS (FCS-A), human serum albumin (HSA) and autologous serum (AS), and of four antibiotics on lymphocyte blast transformation and on lymphocyte proliferation for cytogenetic studies, were evaluated . 3H-thymidine incorporation was measured in the lymphocytes obtained from sixteen healthy adults and stimulated with phytohaemagglutinin (PHA), concanavalin A (Con A), pokeweed mitogen (PWM), PWM + PHA and PWM + Con A . The most efficient protein supplement was AS, although great variability was observed between subjects . HSA came second, while FCS and FCS-A were the least effective . The presence of immunoglobulins did not modify mitogen-induced lymphocyte responses . In unsupplemented media, peak responses to PHA and Con A occurred at lower mitogen concentrations . Furthermore, the addition of the antibiotics tested did not impede blast transformation whether or not a protein supplement was present . This work also showed that for chromosome analysis, protein supplements are necessary for optimum whole-blood lymphocyte cultures and that HSA can replace FCS. Ann Rech Vet, 1987, 18(3), 217 - 25 {Pharmacokinetics of prednisolone administered to cows in the form of a prednisolone acetate solution in dimethyl sulfoxide in association with antibiotics}; Oukessou M et al.; Pharmacokinetic parameters of prednisolone after intramuscular administration of prednisolone acetate as a solution were determined in cattle . Analysis of absorption revealed that a first fraction of the dose (about 20%) was rapidly absorbed with an half time of absorption of 1.76 +/- 0.725 h; the second fraction (about 80% of the dose) was absorbed more slowly with an half time of absorption of 12.3 +/- 3.16 h . Such a process of absorption was different of that described for prednisolone acetate suspension for which rate of absorption was slower . Therapeutic consequences of these kinetic differences were discussed for the use of fixed combination of antibiotics and corticosteroid. G Batteriol Virol Immunol, 1987 Jan-Dec, 80(1-12), 177 - 81 {Protection against experimental infections in mice by an oral vaccine and its combined role when administered with antibiotics}; Gismondo MR et al.; Immunomodulator with significantly modify the immunologic response of the host . The AA . studied the immunologic profile of an oral vaccine to protect the experimental infection in mice and its effect when it was administered with antibiotics . The mice infected with S . enteritidis were protected by the vaccine administered . Also in the group of mice treated with a vaccine and antibiotic combination, the mortality rate was lower than in the untreated groups. Biochem Soc Symp, 1987, 53, 1 - 8 Ribosomal modification and resistance in antibiotic-producing organisms; Cundliffe E; Antibiotic producing organisms defend themselves against their products in a variety of ways including modification of the normal target sites for antibiotic action . In the ribosomal context, some organisms that produce inhibitors of protein synthesis render their own ribosomes refractory to the autogenous drugs via specific methylation of ribosomal RNA . Such hints that antibiotics might normally recognize RNA within the ribosome, complement other data in suggesting that RNA might be intimately associated with--and, in evolutionary terms, might originally have constituted--various functional sites within the ribosome. Scand J Infect Dis, 1987, 19(5), 559 - 67 Infectious complications in patients undergoing marrow transplantation: a prospective randomized study of the additional effect of decontamination and laminar air flow isolation among patients receiving prophylactic systemic antibiotics; Petersen FB et al.; 99 patients with hematological malignancies underwent allogeneic marrow transplantation from HLA-identical sibling donors and were randomized to receive one of two forms of infection prophylaxis while granulocytopenic: (1) prophylactic systemic antibiotics in a conventional hospital room (PSA, 50 patients) or (2) decontamination, isolation in a laminar air flow room and the administration of prophylactic systemic antibiotics (LAF + PSA, 49 patients) . Only 1 patient (3%) in the LAF + PSA group acquired septicemia while granulocytopenic compared to 11 (24%) patients in the PSA group (p less than 0.005) . Three patients (6%) in the LAF + PSA group acquired major localized infections compared to 9 (18%) in the PSA group (p = 0.06) . There was no significant difference in days in hospital post transplant, days of granulocytopenia, days of fever, incidence of acute graft-versus-host disease, interstitial pneumonitis or overall survival . We conclude that the use of prophylactic systemic antibiotics added to decontamination and laminar air flow isolation of patients undergoing marrow transplantation significantly reduces the incidence of septicemia in the granulocytopenic period. Pharmacotherapy, 1987, 7(3), 80 - 6 Determinants of antibiotic-associated hypoprothrombinemia; Schentag JJ et al.; Hypoprothrombinemia is a relatively uncommon event in the hospitalized patient . When it does occur, it often is associated with surgery, dietary vitamin K deficiency, renal dysfunction, malignancy, and broad-spectrum antibiotic therapy . Several mechanisms have been proposed to account for antibiotic-associated hypoprothrombinemia, including eradication of gastrointestinal bacteria, direct inhibition of vitamin K-dependent coagulation, and indirect inhibition of coagulation . The anecdotal reports and comparative studies of antibiotic-associated hypoprothrombinemia were reviewed; these usually implicated broad-spectrum or the use of several antibiotics . The increased frequency of hypoprothrombinemia associated with moxalactam and cefoperazone also raises questions about the role of their N-methylthiotetrazole (NMTT) side chains . The hypoprothrombinemia associated with NMTT antibiotics does not occur in healthy volunteers and is rare in patients without complicating conditions . Although NMTT inhibits vitamin K-dependent carboxylation in vitro, the parent cephalosporins do not . It is not clear whether NMTT-containing antibiotics liberate sufficient amounts of NMTT in vivo to antagonize clotting in patients . Thus, although moxalactam, and possibly cefoperazone, may in some cases be responsible for increases in prothrombin time, most important question for further study is whether the newer NMTT-containing antibiotics pose a risk of hypoprothrombinemia that is greater than that of antibiotics lacking this side chain. Drugs Exp Clin Res, 1987, 13(3), 115 - 24 Relationship between chemical structure of antibiotics and pharmacokinetics; Neuman M; Modifications to the chemical structure of antibiotics can modify nearly all pharmacokinetic parameters: digestive absorption, half-life, protein binding, tissue distribution, metabolic biotransformation, biliary and renal elimination . Examples of increased oral bioavailability are given for beta-lactams, macrolides, tetracyclines, fosfomycin, quinolones and acyclovir . The structural modifications responsible for prolonged or shortened half-life, increased or decreased biliary excretion, increased or decreased renal clearance for the different families of antibiotics are reviewed. Acta Obstet Gynecol Scand, 1987, 66(1), 15 - 8 Prophylactic antibiotics in women with a history of pelvic inflammatory disease undergoing first-trimester abortion; Heisterberg L; In a double-blind controlled trial the effect of prophylactic metronidazole on postabortal infection in women with a history of pelvic inflammatory disease (PID) was assessed . One hundred and thirty-five women were eligible for randomization, of whom 17 were excluded . The regimen consisted of oral metronidazole 400 mg 1 h before the abortion and again 4 and 8 h after, or else placebo . In the placebo group the rate of postabortal PID was 13.0% (7/54) and in the metronidazole group 10.9% (7/64), a nonsignificant difference (p greater than 0.7) . Women in gestational weeks 11-12 had a significantly increased rate of postabortal PID compared with women in weeks 6-10 (p less than 0.005), but this rate was not influenced by the treatment (p greater than 0.2) . Women with parity 1 had a significantly increased rate of postabortal PID compared with women with parity 0 (p less than 0.05), but again the treatment did not influence this rate significantly (p greater than 0.2) . The number of hospital days for women in the metronidazole group did not differ significantly from that in the placebo group (p less than 0.1) . The amount of metronidazole administered for prophylactic and postabortal treatment was significantly greater in the metronidazole group (p less than 0.001) . The amounts of other antibiotics prescribed showed non-significant differences between the two groups (all p-values greater than 0.3). Scand J Infect Dis, 1987, 19(4), 459 - 66 Antibiotic therapy in pneumonia: a comparative study of parenteral and oral administration of penicillin; Fredlund H et al.; An open, randomized study of treatment of radiologically verified community-acquired pneumonia is described . 33 patients were treated with phenoxymethylpenicillin orally in an average dose of 2 g every 8 h, and 36 patients were treated intravenously with benzylpenicillin 3 g every 8 h . When temperature was normalized the antibiotic dose was reduced in both groups to oral phenoxymethylpenicillin in an average dose of 1 g every 8 h . 24 and 26 patients in respective groups completed 10 days of therapy . No statistically significant differences between the two groups were found when compared for duration of fever, hospital stay, CRP, ESR, leukocyte counts and X-ray normalization . In spite of the low number of patients included in this study it gives a clear indication that treatment of pneumonia with penicillin by the oral route results in the same outcome as parenteral treatment when patients suffering from vomiting, diarrhoea and severe illness with respiratory distress are excluded . In addition, oral treatment is cheaper than parenteral and more simple to manage. Vet Med Nauki, 1987, 24(1), 9 - 14 {Morphological changes in broilers produced by feeding antibiotics}; Veselinova A et al.; Morphologic studies were carried out on the liver, kidneys, and small intestine of broiler birds that had been given antibiotics with the feed (virginiamycin, 20.0 ppm, flavomycin, 4.8 ppm, and avotan, 10.0 ppm) in the course of 49 days, kept with a group of controls . The liver of the test birds showed protein and fatty dystrophy, and the kidneys--protein dystrophy . The small intestine showed thinning of the wall and increase in the villi intestinales length . The manifestation of the morphologic changes depended on the amount of the antibiotic taken in . Those of the birds that were offered flavomycin had well manifested lesions, while in birds that were given virginiamycin and avotan only the lesions were more slightly expressed. J Chronic Dis, 1987, 40(5), 429 - 37 The effect of cost sharing on the use of antibiotics in ambulatory care: results from a population-based randomized controlled trial; Foxman B et al.; Little is known about how generosity of insurance and population characteristics affect quantity or appropriateness of antibiotic use . Using insurance claims for antibiotics from 5765 non-elderly people who lived in six sites in the United States and were randomly assigned to insurance plans varying by level of cost-sharing, we describe how antibiotic use varies by insurance plan, diagnosis and health status, geographic area, and demographic characteristics . People with free medical care used 85% more antibiotics than those required to pay some portion of their medical bills (controlling for all other variables) . Antibiotic use was significantly more common among women, the very young, patients with poorer health, and persons with higher income . Use of antibiotics for viral, viral-bacterial, and bacterial conditions did not differ between free and cost-sharing insurance plans, given antibiotics were the treatment of choice . Cost sharing reduced inappropriate and appropriate antibiotic use to a similar degree. J Antibiot (Tokyo), 1987 Jan, 40(1), 60 - 5 Azinomycins A and B, new antitumor antibiotics . III . Antitumor activity; Ishizeki S et al.; Azinomycins A and B, isolated from the culture broth of Streptomyces griseofuscus S 42227, were examined for antitumor activities against P388 leukemia, P815 mastocytoma, B-16 melanoma, Ehrlich carcinoma, Lewis lung carcinoma and Meth A fibrosarcoma . Azinomycin B was markedly effective against the intraperitoneally inoculated tumors such as P388 leukemia, B-16 melanoma and Ehrlich carcinoma . The intraperitoneal administration of azinomycin B showed 57% survivors for 45 days and 193% ILS against P388 leukemia . For Ehrlich carcinoma, azinomycin B gave 161% ILS and 63% survivors for 45 days, but solid tumors such as Lewis lung carcinoma and Meth A fibrosarcoma were not susceptible to repeated injection of this substance . Azinomycin A was somewhat less effective than azinomycin B for the tumor systems tested. J Cancer Res Clin Oncol, 1987, 113(1), 15 - 9 Interaction of anthracycline antibiotics with human neutrophils: superoxide production, free radical formation and intracellular penetration; Schinetti ML et al.; Human neutrophils exposed to 10(-4) M doxorubicin and the derivatives epirubicin and thepirubicin revealed a different intracellular penetration and distribution pattern as demonstrated by fluorescence microscopy and fluorimetric determination of drug intracellular concentration . While doxorubicin was found to be a potent inducer of superoxide generation from resting cells, epirubicin exhibited less superoxide-inducing power . Thepirubicin on the contrary did not show any superoxide-inducing effect . Moreover the anthracyclines tested all inhibited the phorbol ester-stimulated chemiluminescent response to the same extent, which suggested a common target for the drug action . Anthracycline-stimulated superoxide production seems to correlate with the cardiotoxic effects . The most cardiotoxic drug, doxorubicin, is the most potent inducer of superoxide generation, while epirubicin, which is less cardiotoxic, has a relatively limited effect on superoxide production . Thepirubicin which has been shown not to induce delayed cardiomyopathy has no effect on superoxide release from the cells. Int J Immunopharmacol, 1987, 9(5), 567 - 75 Beta-lactam antibiotics and human lymphocyte function: the in vitro effect on blastogenesis, lymphokine production and suppressor cell functions; Rouveix B et al.; The effects of penicillin, cephalothin and cefoxitin on lymphokine production and mitogen stimulation of human peripheral blood lymphocytes and suppressor cell functions in man were studied with concentrations achievable in serum . Penicillin (50 and 100 micrograms/ml) and cephalosporins (50 and 100 micrograms/ml) directly stimulated production of the lymphokine leukocyte aggregating factor (LAgF) by unstimulated lymphocytes and enhanced mitogen-stimulated production of this lymphokine . Neither beta-lactam derivative interfered directly with neutrophil aggregation . Using the same concentration, penicillin did not suppress but had either no effect on or slightly increased the unstimulated and mitogen-stimulated lymphocyte transformation responses, whereas cephalosporins significantly suppressed both responses . Suppression of blastogenesis by the latter could be mediated through suppressor cell enhancement as indicated by the significant suppressed lymphocyte transformation observed while using the supernatant of cephalosporin-stimulated and cultured lymphocytes . This suppressive activity was more pronounced with cephalothin than with cefoxitin while it was not observed with penicillin which rather stimulated thymidine uptake . These findings suggest that enhancement of lymphokine production and suppression of lymphocyte transformation by cephalosporins are not contradictory and reflect a stimulating effect on two different lymphocyte subsets . The enhancement of suppressor function might account for the lower incidence of late hypersensitivity reactions observed in patients treated with the cephalosporins compared with those treated with penicillins. Cytobios, 1987, 49(198-199), 197 - 210 Pre- and post-hatch ultrastructural and metabolic changes in the hatching muscle of turkey embryos from antibiotic and glucose treated eggs; John TM et al.; Hatching muscle of turkey embryos from eggs previously dipped in an antibiotic solution with or without glucose, was studied at three developmental stages, 'knocking', 'pipping' and 'post-hatch' . In both treated and untreated groups, occurrence of relaxed muscle fibres was more characteristic of pre-hatch than post-hatch stages . Glycogen decreased toward post-hatch in all groups while lactate increased in untreated and antibiotic groups . In the antibiotic group, glycogen was lower (all stages) and lactate higher (pre-hatch stages) than in the untreated group . In the glucose-added group, there was no reduction in glycogen, but glycolysis seemed to be further enhanced (as indicated by higher lactate) in pre-hatch stages . Thus, providing eggs with glucose may help maintain higher muscle glycogen level even during active glycolysis . The free fatty acid (FFA) level in the untreated group progressively increased from knocking to post-hatch, indicating mobilization of fat as fuel . The antibiotic group had a higher FFA level than the untreated group during knocking and pipping . In the glucose-added group, FFA at knocking was even higher than that at the corresponding stage in the antibiotic group. Biomed Environ Mass Spectrom, 1987 Jan, 14(1), 29 - 38 Applications of fast atom bombardment mass spectrometry and fast atom bombardment mass spectrometry-mass spectrometry to the maduramicins and other polyether antibiotics; Siegel MM et al.; Fast atom bombardment mass spectrometry (FAB MS) and fast atom bombardment mass spectrometry-mass spectrometry (FAB MS/MS) were used to study the monovalent glycoside polyether antibiotics maduramicin alpha, beta and delta and the maduramicin alpha salts, their derivatives and degradation products . Also, representative compounds from three major classes of polyether antibiotics were studied: the monovalent polyethers, nigericin and monensin A, the divalent polyether lasalocid A and the monovalent glycoside polyethers septamycin, BL580 delta, etheromycin and carriomycin . The respective FAB fragment and decomposition ions were correlated with the known structures . The FAB spectra of all the polyethers contained metal-adduct molecular ions . Protonated molecular ions were absent . All the polyethers having a beta-hemiketal carboxylic acid group produced an abundant ion, often the base peak of the spectra, 62 daltons less than the corresponding metal-adduct molecular ion . The gas phase mechanism proposed for the formation of this fragment ion is an unusual unimolecular reaction which is initiated by an intramolecular proton transfer from the carboxylic acid to the hydroxy group of the beta-hemiketal, and, then followed by the concerted losses of water and carbon dioxide to produce the corresponding polyether olefin. Chemotherapy, 1987, 33(1), 9 - 14 Effects of the monobactam antibiotic aztreonam on platelet function and blood coagulation; Agnelli G et al.; The effects of the new monobactam antibiotic aztreonam on platelet function and blood coagulation were evaluated both in vitro and ex vivo . In the in vitro studies carried out on platelets from 6 healthy volunteers, therapeutic concentrations of aztreonam had no effect on platelet function . Aztreonam inhibited platelet aggregation only at concentrations far in excess of those clinically achievable . In the ex vivo studies carried out in 11 patients with aztreonam-sensitive infections, aztreonam, 1 g t.i.d . intravenously, did not produce any effect on platelet function and blood coagulation . We conclude that therapeutic doses of aztreonam appear not to affect haemostasis. Geriatrics, 1987 Jan, 42(1), 69 - 74 Interactions of oral antibiotics and common chronic medications; Raasch RH; Geriatric patients often require precise dose titration of certain drugs for effective, non-toxic treatment of chronic disease . When short-term antibiotic therapy is required, an oral antibiotic that would minimally disrupt a finely-tuned chronic drug regimen would be most appropriate . Chronic medication-antibiotic interactions are potentially more common with the use of erythromycin, tetracyclines, and sulfonamides . Clinicians should use care, and monitor for drug interactions when these agents are combined with chronically used drugs such as theophylline, warfarin, or carbamazepine. Free Radic Res Commun, 1987, 3(1-5), 141 - 50 Mechanism of the interaction of superoxide ion and ascorbate with anthracycline antibiotics; Afanas'ev IB et al.; The interaction of superoxide ion and ascorbate anion with anthracycline antibiotics (adriamycin and aclacinimycin A) as well as with their Fe3+ complexes has been studied in aprotic and protic media . It was found that both superoxide and ascorbate reduce anthracyclines to deoxyaglycons via a one-electron transfer mechanism under all conditions studied . The reaction of ascorbate anion with adriamycin and aclacinomycin A in aqueous solution proceeded only in the presence of Fe3+ ions; it is supposed that an active catalytic species was Fe3+ adriamycin . It is also supposed that the reduction of anthracycline antibiotics by O2- . and ascorbate in cells may increase their anticancer effect. Trans R Soc Trop Med Hyg, 1987, 81(5), 847 - 9 Topical antibiotics in chronic sickle cell leg ulcers; Baum KF et al.; A randomized, controlled, trial of a topical antibiotic preparation (neomycin, bacitracin, and polymyxin B) was performed in 30 patients with homozygous sickle cell (SS) disease and chronic leg ulceration . Over a period of 8 weeks, the reduction in ulcer size was significantly (P less than 0.05) greater in the treatment group than in the control group . The results suggest that these topical antibiotics may contribute to the therapy of chronic leg ulceration associated with sickle cell disease. Acta Microbiol Pol, 1987, 36(1-2), 39 - 51 Regulation of sulphur amino acids metabolic enzymes in Cephalosporium acremonium strains differing in antibiotic production; Lewandowska M et al.; Three strains of Cephalosporium acremonium with different potential of cephalosporin C production show differences in the levels of sulphur amino acid metabolic enzymes . The regulation of these enzymes is also different in the strains . In the superior producing strain two enzymes directly involved in cysteine synthesis are the least susceptible to repression by methionine . In this strain cystathionine metabolizing enzymes seem to favour cysteine synthesis . Antibiotic producing strains, in contrast to the non-producing strain, are highly sensitive to chromate. Biomed Biochim Acta, 1987, 46(2-3), S16 - 20 Formation of flip sites for phospholipids by introduction of channel-forming antibiotics into the membrane of human erythrocytes; Haest CW et al.; Incorporation into the erythrocyte membrane of channel-forming antibiotics, such as the polyene amphotericin B or the polypeptide gramicidin A, highly accelerates the transbilayer reorientation (flip) of exogenously incorporated lysolecithin . The first enhancement of flip is obtained when about 2 X 10(5) copies per cell are incorporated of each of the antibiotics . An up to 40-fold increase is obtained at about 2 X 10(6) copies per cell . Conversely, pimaricin, a polyene antibiotic which does not form channels probably because it cannot span the lipid bilayer, does not enhance flip . Moreover, the N-formylated analogue of gramicidin, which does not form channels either, does not enhance flip . The results clearly demonstrate the specificity of the flip enhancing effect and indicate a requirement of a focal perturbation of the outer and the inner membrane layer to induce flip by the channel formers . Besides flip enhancement antibiotics increase the rate of cleavage of outer membrane layer phosphatidylcholine by phospholipase A2 . Moreover, amphotericin increases accessibility of inner membrane layer phosphatidylethanolamine to the lipase, whereas gramicidin does not enhance accessibility of this phospholipid . This indicates a more general perturbation of the inner membrane lipid domain by the polyenes. Presse Med, 1986 Dec 20, 15(46), 2358 - 61 {In vitro inhibition of granulopoiesis by beta-lactam antibiotics . Comparison of piperacillin, mezlocillin, ceftriaxone and ceftazidime}; Marie JP et al.; The mechanism of neutropenia induced by beta-lactam antibiotics was explored by studying the action of these drugs on granulopoiesis in vitro . Normal bone marrows were cultivated in the presence of increasing concentrations of piperacillin (10 marrows), mezlocillin, ceftriaxone and ceftazidime (5 marrows each) in order to find out whether these antibiotics exhibited toxicity to granulocyte-monocyte precursors . A dose-dependent inhibition of granulopoiesis was found in all cases . When the doses used were equivalent to maximum plasma concentrations in vivo, inhibition was minimal with piperacillin and mezlocillin and much more pronounced with the cephalosporins . This dose-dependent inhibition suggests that toxicity is involved in the mechanism of neutropenia induced by beta-lactam antibiotics. Vet Rec, 1986 Dec 6, 119(23), 565 - 9 Testing for antibiotic residues in milk; Booth JM et al.; Milk from dairy farms in England and Wales has been tested regularly for antibiotic residues since 1965 . The sensitivity of the test organism was 0.02 iu/ml penicillin or equivalent until the change to 0.01 iu/ml in January 1986 . In 1984-85, 99.6 per cent of the 2,000,000 milk samples tested passed the test and there was an average of 695 failures per month . From 7500 on-farm investigations over the two years 1983-85 the most frequent reasons suggested by farmers for their test failures were not withholding milk for the full withdrawal period (19.3 to 16.5 per cent) and accidental transfer of milk (16.3 to 16.7 per cent) . Lactating and dry cow intramammary antibiotic preparations were held responsible for rather over 50 per cent and 25 per cent respectively of the failures in both years. J Antibiot (Tokyo), 1986 Dec, 39(12), 1651 - 6 PD 124,895 and PD 124,966, two new antitumor antibiotics; Hurley TR et al.; The isolation and characterization of the title antibiotics, which are produced by the same Streptomyces sp., is described . The potent antitumor agent, PD 124,895, is an analog of hydroxyelactocin (PD 114,721) . PD 124,966 is a new member of the depsipeptide family of antibiotics. Chemioterapia, 1986 Dec, 5(6), 400 - 3 Treatment of infections during hematologic malignancies with aztreonam, a new antibiotic; Rizzo SC et al.; Nineteen patients with hematological malignancies (5 malignant lymphomas, 9 acute leukemia and 5 other hematological diseases) were treated with aztreonam alone or in combination for infection . Four out of five patients in the lymphoma group, 6/9 in the leukemia group and 4/5 in the last group were considered cured of their infection . No important clinical side effects or consistent deterioration of hematology and chemistry tests were observed. J Trauma, 1986 Dec, 26(12), 1067 - 72 Tube thoracostomy and trauma--antibiotics or not? LoCurto JJ Jr, Tischler CD, Swan KG, Rocko JM, Blackwood JM, Griffin CC, Lazaro EJ, Reiner DS. Controversy persists regarding the use of antibiotics in association with t tube thoracostomy for trauma patients . We conducted a prospective randomized study of patients requiring tube thoracostomy for pneumo- and/or hemothorax complicating blunt or penetrating thoracic trauma in an attempt to assess the efficacy of prophylactic antibiotic therapy . Fifty-eight patients were included in the study . The control group (Group I) included 28 patients who received no antibiotic therapy: the experimental group (Group II) included 30 patients who received cefoxitin (1.0 gm IV q 6 h) commencing before tube thoracostomy and terminating 12 hours after its removal . The incidence of infectious complications (pneumonia and/or empyema) was recorded . Among the patients not receiving antibiotics, eight of 28 (29%) developed infectious chest complications . Of the patients receiving antibiotics, there was one infectious complication (3%) . This difference is statistically significant (p = 0.0227) . Cultures demonstrated significant conversion from negative to positive both within each group and between groups . The organism most commonly recovered was S . aureus . Our findings strongly suggest that patients requiring tube thoracostomy for trauma, whether blunt or penetrating, should receive the benefit of systemic prophylactic antibiotic therapy. Ann Surg, 1986 Dec, 204(6), 643 - 9 Successful treatment of osteomyelitis and soft tissue infections in ischemic diabetic legs by local antibiotic injections and the end-diastolic pneumatic compression boot; Dillon RS; Thirty-four legs at risk of amputation due to peripheral arterial insufficiency associated with ischemic necrosis, soft tissue infections, osteomyelitis, and variable degrees of peripheral neuropathy were reported in 28 diabetic patients . Amputation had been considered in 27 legs for which standard therapies had failed for the current illness and in two legs in which standard therapy had failed for previous illnesses . Local therapy was the initial form of therapy for five legs in which standard therapy appeared likely to fail . Infection was controlled in all patients with the use of local antibiotics and compression boot therapy . Early leg amputation was avoided in all but one patient . Late leg amputation occurred in two patients who were lost to follow-up care . Osteomyelitis, ischemic necrosis, and advanced soft tissue infection were shown not to be clear-cut indications for amputation in the ischemic diabetic foot. Toxicol Appl Pharmacol, 1986 Dec, 86(3), 430 - 6 The influence of cephem antibiotics on gentamicin nephrotoxicity in normal, acidotic, dehydrated, and unilaterally nephrectomized rats; Furuhama K et al.; Normal, acidotic, dehydrated, or unilaterally nephrectomized rats (Sprague-Dawley) were injected with gentamicin (80 mg/kg/day) alone or in combination with cefoxitin (2 g/kg/day), cephalothin (2 g/kg/day), or cephaloridine (1 g/kg/day) once daily for 10 consecutive days . Serum creatinine levels and renal cortical concentrations of gentamicin were determined and histopathological examination of the kidneys was made . Gentamicin caused marked renal damage in all the groups of rats . In normal rats, all the cephem antibiotics significantly reduced both gentamicin nephrotoxicity and renal gentamicin levels . In acidotic, dehydrated, and unilaterally nephrectomized rats, cefoxitin still significantly reduced gentamicin nephrotoxicity without affecting renal gentamicin concentration, whereas cephalothin and cephaloridine did not show any significant reduction of nephrotoxicity or gentamicin concentration, but rather caused general deterioration of the animals . Hence, the intrinsic nephrotoxic potential of cefoxitin, cephalothin, and cephaloridine may contribute to the difference in the combined effect rather than the concentration of gentamicin in the kidney. J Nucl Med, 1986 Dec, 27(12), 1849 - 53 Effect of antibiotic therapy on the sensitivity of indium-111-labeled leukocyte scans; Datz FL et al.; Although 111In-labeled leukocytes have been shown to be a useful technique for detecting infection, it has been postulated that antibiotic therapy may reduce the sensitivity of the leukocyte scan . Many patients with suspected bacterial infections are placed on antibiotics before a definite site of infection has been identified . Three hundred twelve leukocyte scans on 271 patients were retrospectively reviewed and classified as positive or negative, and as to whether or not they were being treated with antibiotics at the time the leukocyte scan was performed . The overall sensitivity, considering all 312 studies, was 90% . One hundred sixty-nine patient studies were on patients receiving antibiotics; 143 studies were on patients not on antibiotics . The sensitivity of the leukocyte scan was 88.7% in patients on antibiotic therapy; it was 92.1% in those who were not receiving antibiotics . The differences in sensitivity between the two groups were not significantly different (p less than 0.05) . We conclude that antibiotic therapy does not affect the sensitivity of the 111In-labeled leukocyte scan. Antibiot Med Biotekhnol, 1986 Dec, 31(12), 909 - 13 {Pharmacokinetics of amikacin in the perilymph and blood serum . An approach to the comparative evaluation of the potential ototoxicity of aminoglycoside antibiotics}; Dolgova GV et al.; The pharmacokinetics of amikacin in serum and perilymph was studied on guinea pigs treated with its single subcutaneous administrations in doses of 100, 200, 400 and 800 mg/kg . Proportional relation between the values of the areas under the concentration against time curves of the antibiotic in serum and perilymph was shown . It suggested that the level of the antibiotic penetration into the internal ear might be predicted by the area under the concentration against time curve of the aminoglycoside . It was demonstrated that in equitherapeutic doses when D/Deq = 1 aminoglycosides had different areas under the concentration against time curve . Thus, the area under the curve of amikacin was 2.2 times higher than that of sisomicin . It was also demonstrated that the angle coefficient characterizing the relationship between the area under the concentration against time curve in perilymph and the dose standardized with respect to the equitherapeutic value was markedly higher for amikacin than for sisomicin. Antibiot Med Biotekhnol, 1986 Dec, 31(12), 883 - 6 {Problems of the hygienic standardization of antibiotics}; Zel'tser IZ et al.; Some of the results of the development of hygienic standardization of antibiotics are discussed . The main scheme proposed earlier was tested in hygienic investigation of antibiotics of various groups . Separate elements of the scheme were shown to be reliable and approaches to its further improvement were suggested . The trends of promising studies on toxicology of antibiotics aimed at their hygienic standardization are presented. J Appl Bacteriol, 1986 Dec, 61(6), 481 - 9 Role of selective pressure by screening organisms in the development of producer mutant isolates of different antibiotic markers; Basu S et al.; The phenotypes of producer mutant isolates when obtained after mutagenesis of the spontaneous degenerate Aspergillus versicolor N5 by screening on Trichophyton rubrum and those on A . niger G3Br were found to be markedly different . In respect of phenotypic character anti-T . rubrum producer mutant isolates resembled the parental type more closely (which is specifically active against T . rubrum and generally against dermatophytes) than anti-A . niger mutant isolates . This clearly indicates not only the role of selective pressure of the screening organism in the development of a given producer mutant isolate but also shows the possibility of recovery of a producer type of the lost antibiotic marker. Infect Control, 1986 Dec, 7(12), 586 - 92 Prevention of nosocomial infections in marrow transplant patients: a prospective randomized comparison of systemic antibiotics versus granulocyte transfusions; Petersen FB et al.; One hundred twelve patients with hematologic malignancies underwent marrow transplantation from HLA-matched sibling donors and were randomized to receive either prophylactic granulocyte transfusions (PG, 67 patients) or prophylactic systemic antibiotics (PSA, 45 patients) as prophylaxis against nosocomial infections . Patients were treated in conventional hospital rooms and studied until day 100 post-transplant . For the entire study period, 26 patients (39%) in the PG group developed septicemia compared to 15 patients (33%) in the PSA group . Twenty-eight patients (42%) in the PG group developed local major infections compared to 19 patients (42%) in the PSA group . Ten patients (15%) in the PG group developed viral interstitial pneumonitis compared to 6 patients (13%) in the PSA group . None of these differences were statistically significant . There was no difference in the incidence of bacterial or fungal infections or viral interstitial pneumonitis between the two groups during the granulocytopenic or post-engraftment period . There was no difference in the incidence and severity of graft-versus-host-disease (GVHD) . Inability to carry out the prophylaxis was frequent in the PG group, with complications necessitating discontinuance of transfusion in 24% of the recipients and 13% of the donors . The use of PG as an infection prophylaxis modality in marrow transplantation is not supported by this study, as it is difficult to carry out and because PG did not show any advantage over the use of PSA in preventing nosocomial infections. Ann Intern Med, 1986 Dec, 105(6), 924 - 31 Potential for bleeding with the new beta-lactam antibiotics; Sattler FR et al.; Several new beta-lactam antibiotics impair normal hemostasis . Hypoprothrombinemia has occurred frequently with cephalosporins that possess a methylthiotetrazole substitution (cefamandole, moxalactam, and cefoperazone) . The incidence ranges from 4% to 68%, and the risk is greatest in debilitated patients with cancer, intra-abdominal infection, or renal failure . Impaired platelet function caused by perturbation of agonist receptors on the platelet surface has occurred primarily with beta-lactam antibiotics having an alpha-carboxyl substitution (moxalactam, carbenicillin, and ticarcillin) . These antibiotics often cause the template bleeding time to be markedly prolonged (greater than 20 minutes) . Acylureidopenicillins, which lack the alpha-carboxyl marker, impair platelet function less frequently and only modestly prolong the bleeding time . If serious hemorrhage occurs, hypoprothrombinemia associated with methylthiotetrazole-substituted cephalosporins should be treated with fresh frozen plasma . Likewise, dangerous bleeding due to impaired platelet aggregation requires treatment with platelet concentrates. J Biomol Struct Dyn, 1986 Dec, 4(3), 319 - 42 Interactions of quinoxaline antibiotic and DNA: the molecular structure of a triostin A-d(GCGTACGC) complex; Wang AH et al.; The crystal structure of a DNA octamer d(GCGTACGC) complexed to an antitumor antibiotic, triostin A, has been solved and refined to 2.2 A resolution by x-ray diffraction analysis . The antibiotic molecule acts as a true bis intercalator surrounding the d(CpG) sequence at either end of the unwound right-handed DNA double helix . As previously observed in the structure of triostin A-d(CGTACG) complex (A.H.-J . Wang, et . al., Science, 225, 1115-1121 (1984)), the alanine amino acid residues of the drug molecule form sequence-specific hydrogen bonds to guanines in the minor groove . The two central A.T base pairs are in Hoogsteen configuration with adenine in the syn conformation . In addition, the two terminal G.C base pairs flanking the quinoxaline rings are also held together by Hoogsteen base pairing . This is the first observation in an oligonucleotide of . Hoogsteen G.C base pairs where the cytosine is protonated . The principal functional components of a bis-intercalative compound are discussed. Cell Biol Toxicol, 1986 Dec, 2(4), 509 - 11 Effects of beta-lactam antibiotics on eukaryotic cells; Dewdney JM; A symposium on effects of beta-lactam antibiotics on eukaryotic cells was held as part of the 9th International Congress of Infectious and Parasitic Diseases (Munich, Germany, July 1986) . This symposium provided an opportunity to review recent work on the effect of beta-lactam structures on mammalian cells in culture and to speculate on possible clinical implications . This paper is a comment on the subject matter covered by the symposium papers which follow. Poult Sci, 1986 Dec, 65(12), 2314 - 7 A differential response in turkey poults to various antibiotics in diets designed to be deficient or adequate in certain essential nutrients; Buresh RE et al.; Two experiments, each consisting of two trials, were conducted with day-old Nicholas L