Cancer Res, 1983 Jun, 43(6), 2849 - 56 Effects of DNA superhelical changes induced by ethidium bromide on the DNA-degrading activity of two antitumor antibiotics, bleomycin and phleomycin; Huang CH et al.; The effects of changes in the conformational state of DNA on the single-strand and double-strand breakage activity of two antitumor antibiotics, bleomycin (BLM) A2 and phleomycin D1, have been studied by the gel electrophoretic analysis of the drug-degraded PM2 phage superhelical DNA pretreated with an intercalating agent, ethidium bromide (EB) . Both the single-strand and double-strand breakage activities of BLM A2 increased as the negatively superhelical turns of native PM2 DNA were gradually removed by intercalation with increasing EB concentrations . The activities peaked when DNA was completely relaxed and gradually decreased as the higher concentrations of EB twisted DNA into the positively superhelical form . The decrease in breakage activity was not due to any inhibitory effect of EB at higher concentrations, since treatment of the relaxed Form I0 DNA with low EB concentrations also reduced the activity . In contrast to BLM A2, phleomycin D1 responded minimally to DNA conformational changes, which suggested further that the two drugs may react with DNA differently . The differential responses of BLM A2 activity towards different DNA conformational states may have biological implications, since DNA in cells may exist in different conformational states relating to various gene functions . The current study may serve as a model for studying combined effects of intercalative and nonintercalative antitumor antibiotics which are used frequently in combination treatments of cancer. Biochim Biophys Acta, 1983 May 20, 740(1), 80 - 7 Interaction of new anthracycline antibiotics with DNA . Effects on nucleic acid synthesis and binding to DNA; Komiyama T et al.; The effects of various new anthracycline antibiotics on DNA and RNA synthesis were studied using DNA polymerase I (EC 2.7.7.7), RNA polymerase (EC 2.7.7.6) obtained from Escherichia coli and reverse transcriptase obtained from avian myeloblastosis virus . Aclacinomycin A, its analogues, baumycins A1 and A2, adriamycin and daunomycin showed potent inhibitory effects on these polymerases, with calf thymus DNA as template, with IC50 values of 10-30 microM . With poly(rA) x d(pT)10 as template for reverse transcriptase, aclacinomycin A and daunomycin showed IC50 values higher than 500 microM . Baumycins B1, B2, C1, and C2 showed high IC50 values on three polymerases . Addition of excess template DNA to the reaction mixture reversed the inhibitory effect of anthracyclines . Addition of calf thymus DNA to anthracyclines caused a bathochromic and hypochromic change in the visible spectrum . Apparent binding constant for aclacinomycin A, its analogues, and adriamycin were in the range of (1-2) X 10(6) M-1 . Aclacinomycin A and adriamycin also bind to heat denatured DNA, but not strongly to yeast RNA . From these results, the structure-activity relationships of new anthracyclines on DNA binding and polymerase reactions are discussed. Biochem Biophys Res Commun, 1983 May 16, 112(3), 801 - 8 Effects of aminoglycoside antibiotics on the coupling of protein and RNA syntheses in Escherichia coli; Cortay JC et al.; The interdependency of protein and RNA syntheses was studied comparatively in bacteria confronted with amino acid starvation or treated separately with various aminoglycoside antibiotics . By contrast with the concomitant inhibition of macromolecular syntheses in cells deprived of an essential amino acid, RNA production was found to continue in drug-treated cells while protein synthesis was arrested . Such uncoupling process was also observed in bacteria subjected simultaneously to amino acid starvation and treatment with certain antibiotics (neomycin, gentamicin, spectinomycin and kasugamycin) but not with others (streptomycin and kanamycin) . These results were related to the intracellular concentration of guanosine polyphosphates, ppGpp and pppGpp . They were discussed in terms of interaction of aminoglycosides with ribosomes. Cancer, 1983 May 15, 51(10), 1795 - 9 Treatment of erythroleukemia with anthracycline antibiotics and cytosine arabinoside; Tamura K et al.; The introduction of the anthracycline antibiotics and cytosine arabinoside have significantly improved the remission induction rate for patients with acute nonlymphocytic leukemia . Erythroleukemia (M6 by French-American-British classification) has long been considered to be resistant to chemotherapy . Since 1973 we have treated 14 patients with erythroleukemia with daunorubicin 45 mg/m2 or doxorubicin 30 mg/m2 for three days and cytosine arabinoside 100 mg/m2 by continuous infusion for 7 to 10 days . Six complete remissions (43%) were obtained with remission durations of 3+, 4+, 9, 13, 29+, and 35 months . While this remission rate is somewhat lower than that obtained with other types of acute nonlymphocytic leukemia, the combination of anthracycline antibiotics and cytosine arabinoside is clearly effective against erythroleukemia . Five patients treated before mid 1976 died soon after remission induction therapy was started . Four of these five patients were treated for 6 to 9 months with prednisone, halotestin, and/or splenectomy before remission induction chemotherapy was started and three of these patients died of systemic fungal infection, suggesting that these modalities of treatment may interfere with patient tolerance to remission induction therapy . It is suggested that erythroleukemia should be treated with intensive chemotherapy soon after the diagnosis is made. Experientia, 1983 May 15, 39(5), 528 - 30 Paracelsin, a peptide antibiotic containing alpha-aminoisobutyric acid, isolated from Trichoderma reesei Simmons . Part A; Bruckner H et al.; A peptide antibiotic has been isolated from Trichoderma reesei QM 9414 . Although crystalline and uniform in TLC, this antibiotic could be resolved by HPLC into 3 sequence analogues . The close relationship to alamethicin was proved by chemical and spectroscopic methods, and the formation of ion-conducting pores in lipid bilayers. Int J Pept Protein Res, 1983 May, 21(5), 546 - 54 Studies on the structure of a novel peptide antibiotic, K-582; Kawauchi H et al.; A novel peptide antibiotic, K-582, which exhibited significant growth inhibition of Candida, viruses and ascites tumor in mice, was found in the culture medium of a strain of Metarhizium anisopliae by Kondo et al . (J . Antibiotics 33, 535-542 (1980) } . K-582 consisted of two components, designated K-582 A and K-582 B . Threonine, tyrosine, ornithine, and an unusual amino acid were common in both peptides, but lysine was an extra component of K-582 A . The unusual amino acid was identified to be threo-gamma-hydroxy-L-arginine (OHArg) by means of mass, nuclear magnetic resonance and infrared spectrometries of the derivatives and the related compounds . The threonine and the arginine were assigned to be L-configuration, and the ornithine and the tyrosine to be D-configuration in both K-582 A and K-582 B, and the lysine to be L-configuration by comparison of their optical rotatory dispersion spectra with those of standard amino acids . The elucidation of primary structure revealed that they were closely related heptapeptides with the following sequence: K-582 A:H-Arg-OHArg-Orn-Thr-Orn-Lys-Tyr-OH; K-582 B:H-Arg-OHArg-Orn-Thr-Orn-OHArg-Tyr-OH, and had the identical sequence in terms of the configuration of their constituents, namely L-L-D-L-D-L-D. J Antibiot (Tokyo), 1983 May, 36(5), 468 - 70 DC-52, a novel antitumor antibiotic . 2 . Isolation, physico-chemical characteristics and structure determination; Takahashi K et al.; DC-52, C18H22N2O4, is a new antitumor antibiotic produced by Streptomyces melanovinaceus nov . sp . The structure of DC-52 has been determined by consideration of spectral data . It has the novel skeleton, 8,11-iminoazepinoisoquinoline. Antimicrob Agents Chemother, 1983 May, 23(5), 649 - 52 Detection of endotoxin in antibiotic solutions with Limulus amoebocyte lysate; Case MJ et al.; Twenty-eight antibiotics were tested with the Limulus amoebocyte lysate assay to determine their non-inhibitory concentrations (NICs) . The Limulus amoebocyte lysate assay was found to be a valid test for most of the antibiotics tested; the NICs were found to be greater than the minimum valid test concentrations . Borderline results were obtained with cefamandole nafate and neomycin sulfate . Polymyxin B and colistimethate contained too much endotoxin to permit determination of NICs . The NIC of tetracycline hydrochloride was dependent on the initial concentration of antibiotic . This dependence was most likely caused by the amount of base required to adjust the pH before testing. J Antibiot (Tokyo), 1983 May, 36(5), 478 - 83 Studies on WF-3161, a new antitumor antibiotic; Umehara K et al.; WF-3161 is an antitumor antibiotic produced by a strain of fungus, Petriella guttulata . The antibiotic was purified by solvent extraction and a combination of silica gel and reverse phase column chromatography . The chemical structure of the antibiotic (C31H44N4O6, mp 181-183 degrees C) was found to be a cyclic tetrapeptide consisting of phenylalanine, leucine, pipecolinic acid and 2-amino-8-oxo-9,10-epoxydecanoic acid . WF-3161 inhibited the growth of Trichophyton asteroides . It prolonged survival period of mice bearing leukemia P-388 with a high therapeutic index. Can Med Assoc J, 1983 May 1, 128(9), 1075 - 8 Auditing antibiotic use in a teaching hospital: focus on cefoxitin; Jewesson PJ et al.; The prevalence and nature of antibiotic misuse in a major teaching hospital was assessed by means of a quality-of-use audit . Cefoxitin was chosen for study . The use of cefoxitin increased rapidly during the study period, accounting for 17.7% ($15300) of the pharmacy's costs for cephalosporins during the first year of its availability but 47.7% ($60707) during the second year . Cefoxitin was inappropriately used for 43% of the patients receiving it during the first 2-month audit period and for 25% of those receiving it during the second audit period, 1 year later (p less than 0.01 by chi-square analysis). Vopr Med Khim, 1983 May-Jun, 29(3), 134 - 6 {Chromatographic method for quantitative determination of cordycepin in rat brain tissue after intraperitoneal injection of the antibiotic}; Musaev NI et al.; A procedure is developed for quantitative estimation of intraperitoneally administered unlabelled cordycepin in acid soluble pool isolated from rat brain tissue . The fraction containing 2'- and 3'-deoxyriboadenosine (cordycepin) in acid soluble pool of rat brain was isolated after consecutive chromatography on columns of Dowex 1 X 8, Dihydroxyboryl-SP 500 and Sephasorb-HP . At the same time, 2'-deoxyriboadenosine was isolated from the acid soluble pool fraction of control animals . Content of the antibiotic in brain tissue was estimated by its difference in these two fractions (control/experiment). Dis Colon Rectum, 1983 May, 26(5), 310 - 13 Prophylactic antibiotics in elective colorectal surgery; Portnoy J et al.; In an effort to determine whether or not the addition of parenteral antibiotics to orally administered erythromycin and neomycin would diminish postoperative septic complications in elective colorectal operations, a randomized, double-blind, controlled trial was conducted comparing three groups . All patients received vigorous preoperative mechanical bowel preparation, 3 g erythromycin and 3 g neomycin orally, the day prior to operation . Patients in Group O received three doses of saline intravenously as placebo, patients in Group C received cefazolin, 1 g, immediately preoperatively and 1 g every 6 hours postoperatively, intravenously, for two doses, and patients in Group T received a single immediate preoperative dose of 6 g of ticarcillin intravenously and two saline placebo doses intravenously, postoperatively . The patients' progress was followed in the hospital and for one month postoperatively . Septic complications occurred in 35 per cent of patients in Group O, 7 per cent of patients in Group C, and 5 per cent of patients in Group T . Wound infections comprised most of these complications, occurring in 29 per cent of Group O, 4.7 per cent of Group C, and 2.3 per cent of Group T patients . Thus, the addition of either parenteral cefazolin or ticarcillin in this study significantly reduced wound infections in elective colorectal surgery. Surv Ophthalmol, 1983 May-Jun, 27(6), 353 - 73 Prophylactic antibiotics for ophthalmic surgery; Starr MB; Preoperative or immediately postoperative antibiotics have been used by ophthalmic surgeons routinely as prophylaxis for postoperative endophthalmitis . The rationale for such prophylaxis, as the evidence which supports its efficacy are well founded . The optimal choice of antibiotics, however, from the standpoints of efficacy, delivery (route, dosage, and frequency of administration), adverse reactions, and cost is far less well established . This review considers these issues in the context of a critical evaluation of the pertinent literature. Arch Biochem Biophys, 1983 May, 223(1), 68 - 75 Kinetics of anthracycline antibiotic free radical formation and reductive glycosidase activity; Gutierrez PL et al.; Adriamycin free radical anion concentrations have been correlated with production of 7-deoxyadriamycin aglycone in a reaction catalyzed by NADPH-cytochrome c reductase . The free radical species is detected by electron spin resonance (ESR) spectroscopy and quantified by double integrations . The 7-deoxyaglycone product is isolated by thin-layer chromatography (TLC) and quantified by fluorometry . As the concentration of adriamycin increases, a concomitant increase in aglycone and free radical levels occurs . These results as well as those with inhibitors Vitamin K3, Vitamin E, and 5,5-dimethyl-1-pyrroline-1-oxide (DMPO) point to an obligatory free radical intermediate in the metabolism of adriamycin . DMPO inhibits the reaction under aerobic conditions only, and shows no effect under anaerobiosis at the concentrations studied here . Vitamin E and aerobic DMPO act as free radical scavangers, while Vitamin K3 competes for the reducing power of NADPH in the NADPH-cytochrome c reductase system. Antimicrob Agents Chemother, 1983 May, 23(5), 757 - 65 Use of a temperature-sensitive, protoplast-forming Neurospora crassa strain for the detection of antifungal antibiotics; Selitrennikoff CP; Protoplasts of the temperature-sensitive osmotic-1 mutant of Neurospora crassa grew and divided as cell wall-less cells when incubated under certain conditions at 37 degrees C . Each protoplast regenerated cell wall and formed a mycelium when the temperature was shifted to 22 degrees C . Cell wall regeneration, but not cell growth, was prevented by the inhibition of cell wall assembly functions . Thus, the inhibition of cell wall regeneration could serve as an indicator of the mode of action of antibiotic drugs . A method for detecting cell wall-inhibiting antifungal compounds with osmotic-1 protoplasts is described. Schweiz Med Wochenschr, 1983 Apr 16, 113(15), 558 - 9 {Should antibiotic prevention be used in biliary tract surgery?}; Gruber UF et al.; A prospective, controlled, double-blind, randomized multicentre trial in Switzerland has been conducted to investigate the effectiveness of 5 g mezlocillin given during induction of anesthesia for prevention of infectious complications in biliary tract surgery . All adults undergoing elective or emergency surgery were included . Single-dose prevention reduces the incidence of wound infections from 10% to 4%, but does not reduce other kinds of infectious complications . The incidence of wound infections in the control group in Switzerland is only about half that in other countries . It is concluded that administration of single-dose mezlocillin to all patients in this type of surgery is justified . On the basis of risk factors it is impossible to predict reliably the patients who do not need protection. Antibiotiki, 1983 Apr, 28(4), 254 - 8 {Quantitative determination of the antibiotic tobramycin using high-performance liquid chromatography}; Rubasheva LM et al.; Separation of the main components of the nebramycin complex of apramycin, kanamycin B and tobramycin was achieved in the form of their 2,4-dinitrophenyl derivatives . A chromatograph SR 8000 of 'Spectra-Physics" and a column 'Sperisorb C6" (4.6 X 250 mm) with the granule size of 5 micrometers were used in the study with the mobile phase of acetone-trisbuffer, pH 7 in a ratio of 65 to 35, the flow rate of 1 ml/min, a temperature of 35 degrees C and detection at lambda 350 nm . Quantitative determination of the tobramycin purity level was performed with an equation developed for the given conditions . The purity levels of the reference tobramycin base and its sulfate were estimated . The results of the estimation corresponded to the data of biological titration. J Antibiot (Tokyo), 1983 Apr, 36(4), 429 - 34 Pock forming plasmids from antibiotic-producing Streptomyces; Murakami T et al.; Pock forming ability of fifteen plasmids isolated from antibiotic-producing Streptomyces was examined with polyethylene glycol mediated protoplast transformation . Four plasmids (pSF765, pSF689, pSF674 and pSF601) were found to have pock forming ability on Streptomyces lividans 66 . Each putative transformants isolated from the center of pock regions harbored plasmids with same restriction enzyme cleavage sites as original plasmids . The plasmids from the transformants produced pock, which were morphologically identical to the original plasmids . Transformation frequency of S . lividans 66 with pSF689 from S . lividans 66 was at least 500-fold higher (5 x 10(5) transformants per 1 microgram DNA) than that with the plasmid isolated from the original strain (10(3) transformants per 1 microgram DNA) . In case of pSF765 the transformation frequency was not changed (about 10(5) transformants per 1 microgram DNA) by replications in S . lividans 66 . Expanded restriction enzyme maps for the four plasmids are reported. Arch Neurol, 1983 Apr, 40(4), 209 - 12 Cyanotic congenital heart disease with suspected stroke . Should all patients receive antibiotics? Kurlan R, Griggs RC. Two patients with cyanotic congenital heart disease (CHD) and erythremia were seen for abrupt onset of focal neurologic deficits and/or seizure without signs of infection or increased intracranial pressure . Clinical features and initial computed tomography (CT) in both cases suggested stroke . Subsequent CT scans demonstrated cerebral abscess, proved at operation . Review of records of patients with CHD at the University of Rochester (NY) Medical Center from 1965 to 1981 disclosed 12 cases with brain abscess but only two cases with aseptic cerebral infarction . All but one patient with abscess were cyanotic . One third of patients with abscess had a clinical picture suggesting stroke . Clinical or radiologic features of half the cases indicated that cerebral infarction may have led to abscess formation . Diagnosis of brain abscess and immediate antibiotic therapy should be strongly considered in patients with cyanotic CHD who suffer a suspected cerebral infarction. Antibiotiki, 1983 Apr, 28(4), 266 - 70 {Characteristics of the circular dichroism spectra of liquid crystals formed from DNA complexes with antibiotics}; Evdokimov IuM et al.; Compact particles were formed from low molecular DNA in water-salt solutions (0.3 M NaCl, pH 6.7) containing polyethylene glycol . The DNA molecules in these particles were in the mesophase (liquid crystalline) state characterized by an intensive negative bond in the circular dichroism (CD) spectrum . Binding of DNA to anthracycline antibiotics (daunomycin, aclacynomycin), oligopeptide antibiotics (distamycin, nethropcin) and ethidium bromide with subsequent formation of liquid crystals from such complexes was accompanied by appearance of CD spectra with characteristic features of the respective antibiotic groups . The characteristic features of the CD spectra allowed distinguishing various antibiotics. J Antibiot (Tokyo), 1983 Apr, 36(4), 383 - 90 Biosynthesis of the antitumor antibiotic CC-1065 by Streptomyces zelensis; Hurley LH et al.; The biosynthesis of the antitumor antibiotic, CC-1065, has been investigated by radioactive isotope techniques, in combination with chemical degradation of CC-1065 . Tyrosine, dopa, serine and methionine (S-CH3 group) have been shown to be precursors of CC-1065 . Tyrosine is proposed to be a precursor of all three benzodipyrrole subunits, while dopa is only apparently incorporated into subunits B and C . Serine is postulated to contribute three 2C units, with loss of C-1, to all three subunits of CC-1065 . The S-CH3 group of methionine probably contributes four C-1 units to CC-1065 of which one is incorporated with considerable loss of tritium, most probably into the cyclopropane ring of subunit A. J Antibiot (Tokyo), 1983 Apr, 36(4), 351 - 4 Demethoxyrapamycin (AY-24,668), a new antifungal antibiotic; Sehgal SN et al.; Demethoxyrapamycin is a new antifungal antibiotic which is co-produced with rapamycin by Streptomyces hygroscopicus . It was isolated as a minor component during recovery of rapamycin . Its antifungal and antitumor activity is compared with that of rapamycin. Gynecol Oncol, 1983 Apr, 15(2), 201 - 6 A prospective randomized study of doxycycline as a prophylactic antibiotic in patients undergoing radical hysterectomy; Rosenshein NB et al.; A prospective randomized study was undertaken to evaluate doxycycline as a prophylactic antibiotic in patients undergoing radical abdominal hysterectomy and pelvic lymphadenectomy . Although 69 patients were initially randomized, 64 patients (34 study, 30 control) are the basis of this report: 5 patients were omitted because large pelvic lymph nodes positive for tumor were found at laparotomy and radical hysterectomy was abandoned . The two study groups were similar in both preoperative and operative risk factors . There was a statistically significant reduction in the 7- and 14- day febrile index in the doxycycline group . The rate of cuff and/or pelvic cellulitis was 2.3 times higher in the control group . Thus, single-dose doxycycline as a prophylactic antibiotic reduced both febrile morbidity and the rate of serious infections in the radical hysterectomy patient. Arch Ophthalmol, 1983 Apr, 101(4), 644 - 7 Effect of topical antibiotic solutions on corneal epithelial wound healing; Stern GA et al.; The eight topical antibiotic solutions that we use most frequently were tested for their effect on corneal epithelial wound healing in the rabbit . Five percent cefazolin sodium and a mixture of neomycin sulfate, polymyxin B sulfate, and gramicidin (Neosporin) had the least effect on epithelial healing rates and quality of healing, 10% sulfacetamide sodium and an artificial tear had intermediate effects, and gentamicin sulfate, tobramycin, and chloramphenicol were the most toxic . No substantial differences were found between gentamicin and the newer aminoglycoside, tobramycin, and the "fortified" preparations of these two drugs did not seem to be more toxic than the 0.3% solutions . Therefore, topical antibiotic solutions vary in their effects on the corneal epithelium, and not all antibiotics should be considered innocuous when used in the treatment of epithelial defects. Bioorg Khim, 1983 Apr, 9(4), 556 - 60 {Free radical mechanism of action of pyrimido-triazine antibiotics}; Orlov VS et al.; EPR spectra of anion radicals were recorded as a result of chemical or enzymatic reduction at various pH of the pyrimido-triazine antibiotics . These anion radicals easily form superoxide radicals in the presence of oxygen . It is supposed that a higher selectivity of reumycin action is due to difference in the redox potentials of the neutral and ionized antibiotic forms . A possibility of enhance the reumycin potency may involve the pH lowering inside the tumor cells - for example, by glucose injections. FEBS Lett, 1983 Mar 21, 153(2), 320 - 4 Conformation of antibiotic X-537A (lasalocid-A) and its calcium complex in acetonitrile solvent using circular dichroism spectroscopy; Vishwanath CK et al.; The calcium binding characteristics of antibiotic X-537A (lasalocid-A) in a lipophilic solvent, acetonitrile (CH3CN), have been studied using circular dichroism (CD) spectroscopy . The analysis of the data indicated that in this medium polar solvent, X-537A forms predominantly the charged complexes of stoichiometries 2:1 and 1:1, the relative amounts of the two being dependent on {Ca2+} . The conformations of the complexes, arrived at on the basis of the data, seem to indicate a rigid part encompassing Ca2+, liganded to 3 oxygens of the molecule, viz., the carbonyl, the substituted tetrahydrofuran ring and the substituted pyran ring oxygens (apart from, possibly, the liganding provided by nitrogen atoms of the solvent molecules), and a flexible part consisting of the salicylic acid group of the molecule. Antibiotiki, 1983 Mar, 28(3), 195 - 8 {Determination of the biological activity of antibiotics by using dry nutrient media}; Grigor'eva VM et al.; The possibility of using available dry nutrient media Nos . 5 to 12 in assays of antibiotic biological activity with the agar diffusions method was studied with respect to benzylpenicillin, gramicidin S, kanamycin sulfate, kanamycin B, oleandomycin, novobiocin, tetracycline and erythromycin . The dry media were used instead of the respective media prepared with meat hydrolyzate . Optimal conditions of the assays on such media were determined. Ann Otol Rhinol Laryngol, 1983 Mar-Apr, 92(2 Pt 1), 178 - 82 Alteration of aminoglycoside antibiotic ototoxicity: effect of semistarvation; Prazma J et al.; The effect of semistarvation on the toxicity and ototoxicity of tobramycin sulfate (TO) and gentamicin sulfate (GE) was investigated in guinea pigs by electrophysiological and histopathological methods . The presented data has shown that the toxicity and ototoxicity of aminoglycoside antibiotics is substantially increased when guinea pigs were semistarved . Our results should also warn researchers using semistarvation in their conditioning experiments which investigate the toxicity of different chemicals . Toxicity was greater in GE- than TO-treated animals, which caused the GE-treated animals to die during treatment or shortly after treatment . Thus, TO should be preferentially used because it has been shown to be less toxic and ototoxic in normal and altered nutritional conditions. J Antibiot (Tokyo), 1983 Mar, 36(3), 283 - 8 Improvement of macrolide antibiotic-producing streptomycete strains by the regeneration of protoplasts; Ikeda H et al.; Three macrolide antibiotic-producing strains, the spiramycin producer Streptomyces ambofaciens, the tylosin producer Streptomyces fradiae, and the cirramycin producer Streptomyces cirratus easily formed protoplasts when treated with lysozyme in hypertonic medium . Each type of protoplast was regenerated to a mycelial form at a frequency of 90 to 100% in regeneration medium supplemented with a plasma expander . In the spiramycin producer S . ambofaciens and the tylosin producer S . fradiae, antibiotic productivities of the regenerated progeny were drastically changed . Some regenerated progeny from the three strains gave higher production . One from S . ambofaciens showed about twice the productivity of the original strain and one obtained after two rounds of protoplast regeneration from S . fradiae produced about three times as much as the original strain. J Antibiot (Tokyo), 1983 Mar, 36(3), 276 - 82 Studies on tomaymycin . II . Total syntheses of the antitumor antibiotics, E-and Z-tomaymycins; Tozuka Z et al.; The total syntheses of naturally occurring E-tomaymycin (1E) and its olefinic geometrical isomer, Z-tomaymycin (1Z) are described . The Z-isomer was found to have the same anti-bacterial activity as E-isomer (1E). J Antibiot (Tokyo), 1983 Mar, 36(3), 217 - 25 Ro 22-5417, a new clavam antibiotic from Streptomyces clavuligerus . III . Absolute stereochemistry; Muller JC et al.; The complete stereostructure of the new antibiotic Ro 22-5417 has been established as 3-{(3S,5S)-7-oxo-1-aza-4-oxabicyclo{3.2.O}hept-3-yl}-L-alanine . This result together with the synthesis of an (3R,5R)-L-analog allowed us to postulate that clavams require the R-configuration at the ring juncture for beta-lactamase inhibitory activity, while the opposite S-stereochemistry is essential for antifungal activity. Surg Gynecol Obstet, 1983 Mar, 156(3), 289 - 94 A prospective random study of a single agent versus combination antibiotics as therapy in penetrating injuries of the abdomen; Crenshaw C et al.; One hundred patients undergoing operation for penetrating and potentially contaminated wounds of the abdomen were given cefamandole or a combination of cephalothin-tobramycin by a random, single blind method as preventive therapy . Results were evaluable for 49 patients receiving cefamandole for a success rate of 93.9 per cent . The 45 evaluable results in the second group had a success rate of 88.9 per cent . Those in the single therapy group also required fewer days of treatment and of hospital confinement, resulting in lower per patient cost . Results of this study show cefamandole to be an efficacious alternative for surgeons seeking a single agent therapy. J Vet Pharmacol Ther, 1983 Mar, 6(1), 33 - 40 Encapsulated forms of slow-release dry cow products of rapidly absorbed antibiotics; Linder C et al.; The persistence of chloramphenicol, cephacetrile, and clindamycin in the udders of dry cows was studied after drying-off therapy with salts of these antibiotics suspended in conventional oil bases . Antibiotic activity was not found in dry udder secretions collected 3-5 days after treatment . After equivalent doses of encapsulated formulations of chloramphenicol were suspended in the same oil bases and infused at drying-off, most of the drug remained bound within the microcapsules; chloramphenicol concentrations higher than 10 micrograms/ml secretion were maintained for 3-4 weeks, but upon release from the microcapsule, the free drug was very quickly absorbed from the udder . Microcapsulated formulations of cephacetrile and clindamycin were infused at drying-off, suspended in the same type of oil base and at similar doses to the non-capsulated preparations . The concentrations of free drug in the secretions remained constant over a period of 2-3 weeks, although total drug (bound and free) concentrations in the udder, which were much higher than free drug levels, were progressively and markedly reduced . It appeared that after infusion of the microcapsulated preparations of cephacetrile and clindamycin, rates of drug release from the depot were equal to the rates of absorption of free drug from the udder. Int J Clin Pharmacol Ther Toxicol, 1983 Mar, 21(3), 109 - 14 Comparative study by scanning electron microscopy on vestibular toxicities of dibekacin, ribostamycin, and other aminoglycoside antibiotics in guinea pigs; Sato K et al.; The vestibular toxicities of dibekacin, ribostamycin, gentamicin, and streptomycin were compared in guinea pigs . The animals were given the drugs for 21 days, examined for functional disturbances by electronystagmography (ENG), and then killed to observe morphologic changes in the vestibular sensory hairs on scanning electron microscopy (SEM) . The degree of functional impairment was rated according to the duration of the postrotatory nystagmus and classified into three categories: normal, slight impairment, and severe impairment . The results of the SEM examination were similarly classified into three categories by severity of the degenerative changes in the vestibular sensory hairs, i . e., bending, fusion, ballooning, giant hair formation, or disappearance . Under these experimental conditions, the results of ENG and SEM observations showed good correlation and indicated that the vestibular toxicity was highest in the streptomycin-treated animals and lowest in the dibekacin- or ribostamycin-treated animals. Antibiotiki, 1983 Mar, 28(3), 163 - 7 {Multiplication of a DNA fragment in Streptomyces antibioticus--producer of oleandomycin}; Orlova VA et al.; Two strains of Str . antibioticus producing oleandomycin were studied . Strain 326 was obtained from the initial laboratory strain and strain 1607 from strain 326 as a result of multistage selection aimed at increasing the antibiotic production capacity . Extrachromosomal ring DNA could be identified in strain 1607 . The identified DNA was designated as eSA1 or extrachromosomal element of Streptomyces antibioticus 1 . The molecular weight of this DNA is 21.3 Md . It is represented by 1 copy per chromosome . No eSA1 was isolated from strain 326 at CsCl-EtBr gradient . Hybridization studies according to Southern with the use as a probe of 32-eSA1 DNA showed that strain 326 contained 1 copy of eSA1 per chromosome in the integrated state . The hybridization studies, electron microscopy and analysis of the total DNA in CsC1-EtBr gradient showed that eSA1 in strain 1607 was tandemly multireplicated in the chromosome content . In the autonomous state its number was approximately equal to 1 copy per chromosome . The presence of eSA1 in strain 1607 in the autonomous state probably results from its segregation during homologous recombination due to tandem multireplication . The data are indicative of multiplication in strain 1607 of the chromosome fragment 23.3 Md in size . It is suggested that an increase in the oleandomycin production capacity of strain 1607 is associated with multiplication of the DNA fragment (eSA1) containing the genes determining production of the antibiotic. Surg Gynecol Obstet, 1983 Mar, 156(3), 323 - 5 The role of prophylactic antibiotics in appendectomy using delayed primary closure; Gray DW et al.; A prospective randomized trial of prophylactic antibiotics in 202 patients undergoing appendectomy is reported upon . The antibiotics used were metronidazole and cephradine . Half of the patients received antibiotics preoperatively . The other half received antibiotics at operation only upon finding perforation, gangrene or pus formation . All wounds were treated by delayed primary closure . No instance of wound infection, defined as abscess formation or cellulitis, occurred in either group . Antibiotics given prophylactically in every instance appear to have no advantage in preventing wound infection when delayed primary closure is used. Biochemistry, 1983 Mar 1, 22(5), 1107 - 13 Kinetics for exchange of the imino protons of the d(C-G-C-G-A-A-T-T-C-G-C-G) double helix in complexes with the antibiotics netropsin and/or actinomycin; Pardi A et al.; The lifetimes for exchange of the imino protons in the dodecanucleotide d(C-G-C-G-A-A-T-T-C-G-C-G) upon binding of netropsin and/or actinomycin have been measured by proton nuclear magnetic resonance experiments . At high temperature these lifetimes were found to measure the lifetimes for opening of the base pairs in the double helix . Comparison of the opening rates in the dodecamer with those in the complex with netropsin (which binds at the -A-A-T-T- sequence) shows that there is not only a large kinetic stabilization of the A . T base pairs at the binding site but also a significant stabilization of the G . C base pairs adjacent to the netropsin binding site . For the complex with actinomycin, which intercalates at the G-C sites in the double strand, the lifetimes of the base pairs at the binding site increase upon binding of actinomycin, and the A . T base pairs in the central core are slightly kinetically destabilized by the actinomycin binding . The activation energies for exchange of the imino protons were also measured in the complexes and indicate that the mechanism for exchange of the imino protons is individual base-pair opening, where one base pair opens independently of the others . The effects of drug binding on the dynamics of individual base pairs in a double-stranded helix are discussed. Arch Surg, 1983 Feb, 118(2), 205 - 13 Penetration of eight beta-lactam antibiotics into the peritoneal fluid . A pharmacokinetic investigation; Wittman DH et al.; Serial serum and peritoneal fluid samples were taken after intravenous injection of cefuroxime sodium, cefoxitin sodium, cefotaxime sodium, cefoperazone sodium, ceftazidime, moxalactam disodium, mezlocillin sodium, and piperacillin sodium . Time-concentration curves were obtained for both pharmacokinetic compartments . The geometric mean of peritoneal fluid concentrations from eight to ten patients was used to define the time-concentrations curve for each substance . Serum pharmacokinetic values were calculated using an open two-compartment model . The concentrations (Cps) were calculated from peritoneal fluid concentrations by quadratic interpolation . The time for which one fourth of the Cp (Cp1/4) is maintained within the peritoneal cavity varied according to the substance and can be used to estimate dosage intervals . The Cp1/4 was compared with the minimal inhibitory concentrations for 1,344 pathogens encountered in 415 intra-abdominal infections from 31 studies. J Antibiot (Tokyo), 1983 Feb, 36(2), 131 - 41 Biosynthesis of the macrolide antibiotic tylosin . A preferred pathway from tylactone to tylosin; Baltz RH et al.; The efficiencies of bioconversion of twenty-three potential intermediates in the biosynthesis of tylosin were determined with a mutant strain blocked only in tylactone biosynthesis . The results indicated that tylactone, the first intermediate excreted by Streptomyces fradiae, is converted to tylosin by a preferred sequence of reactions which include: (1) addition of mycaminose to the C-5 hydroxyl position of the lactone; (2) hydroxylation of the C-20 methyl group to a hydroxymethyl group; (3) dehydrogenation of the C-20 hydroxymethyl group to a formyl group; (4) hydroxylation of the C-23 methyl group to a hydroxymethyl; (5) addition of 6-deoxy-D-allose to the C-23 hydroxymethyl group; (6) addition of mycarose to the 4'-hydroxyl group of mycaminose; (7) addition of a methyl group to the 2"'-hydroxyl position of demethylmacrocin, and (8) addition of a methyl group to the 3"'-hydroxyl position of macrocin to produce tylosin . The intermediates which lacked both neutral sugars (mycarose and 6-deoxy-D-allose) were biologically unstable, and substantial quantities of these compounds were degraded during standard bioconversion experiments . However, the amount of one such intermediate (O-mycaminosyltylonolide) degraded was substantially reduced when low concentrations of the compound were used for bioconversion, and under these conditions, much higher efficiencies of bioconversion to tylosin were obtained . We have shown that a mutant blocked in hydroxylation of the C-20 methyl group is also blocked in the further dehydrogenation of the C-20 hydroxymethyl group to a formyl group, and have confirmed in in vitro studies that the 2"'-O-methylation of demethylmacrocin must proceed the 3"'-O-methylation of macrocin to produce tylosin. J Infect Dis, 1983 Feb, 147(2), 341 - 51 Interaction of ischemic and antibiotic-induced injury in the rabbit kidney; Browning MC et al.; The tubular necrosis produced by transient unilateral ischemia, three toxic cephalosporins, and the aminoglycoside neomycin were studied separately and in different combinations in the rabbit kidney . It was found that (1) mildly damaging transient ischemia (25 min) and a minimally toxic dose of the rapidly secreted cephalosporin cephaloglycin (60 mg/kg of body weight) are synergistically damaging; (2) there is no synergy between ischemia and the nonsecreted cephalosporin cephaloridine (90 mg/kg); and (3) ischemia and neomycin (100 mg/kg per day for three days) are not additively damaging, but the aminoglycoside has an additive effect with the combined insults of ischemia and cefazolin (500 mg/kg) . Studies of transport showed that ischemia potentiates cephalosporin toxicity probably because it increases postischemic antibiotic concentrations in proximal tubular cells and that this increased uptake is the result of transiently augmented tubular secretion . Although this ischemic protocol reduced inulin clearance by 40%, it increased cephaloglycin secretion by an amount more than sufficient to overcome the decrease in filtration. Am J Surg, 1983 Feb, 145(2), 209 - 12 Prophylactic antibiotic wound irrigation in gastric, biliary, and colonic surgery; Lord JW Jr et al.; Intermittent intraoperative antibiotic irrigation from the beginning of an operative procedure to its completion is a valuable supplement to hospital and operating room cleanliness and to good surgical technique . A prospective, randomized, double-blind study of 200 patients undergoing clean-contaminated operations on the gastrointestinal tract demonstrated a marked reduction in the incidence of postoperative wound infection and absolute prevention of postoperative peritonitis. J Appl Biochem, 1983 Feb-Apr, 5(1-2), 53 - 8 Free radical damage to polyene antifungal antibiotics: changes in biological activity and thiobarbituric acid reactivity; Gutteridge JM et al.; Polyene antifungal antibiotics contain thiobarbituric acid-reactive substances suggestive of the presence of peroxidic compounds . These peroxides appear to play no part in the drug's antifungal activities . The polyenes were relatively stable to further oxidation in air, but lost biological activity and native ultraviolet absorption upon irradiation with ultraviolet light or incubation with iron salts . No evidence was found for the participation of hydroxyl radicals in the observed damage to the polyene molecules . However, organic oxygen radicals were implicated and protection against ferrous salt dependent damage could be afforded by the addition of the antioxidant propylgallate. J Appl Bacteriol, 1983 Feb, 54(1), 77 - 83 Incidence of antibiotic-resistant Escherichia coli in milk produced in the west of Scotland; Johnston DW et al.; Antibiotic-resistant Esch . coli were found in 10.6% of milk samples collected from 998 farms in the west of Scotland . The incidence of both Esch . coli and antibiotic-resistant Esch . coli in milk was higher when the cattle were housed day and night than when they were outdoors . Of the 1125 Esch . coli isolates tested 22.2% were antibiotic resistant and of these 42.4% were resistant to more than one antibiotic . Escherichia coli carrying up to six resistance determinants were isolated . The possible implications to animal and human health are discussed. Pathol Biol (Paris), 1983 Feb, 31(2), 77 - 9 {Results of a multicenter study of antibiotic sensitivity}; Dabernat H; The results of a multicenter collaborative study on the antibiotic susceptibility of H . influenzae and H . parainfluenzae are showed . 4.5% of H . influenzae strains were beta-lactamase producing strains, they were isolated from sputum, CSF (7.5%), epiglottitis (20%); 3.5% and 0.2% of the strains were resistant to tetracycline and chloramphenicol respectively . The resistant strains belonged to the various biotypes and serotypes . 11% of H . parainfluenzae strains were beta-lactamase producing strains and 7% were resistant to tetracycline. Antimicrob Agents Chemother, 1983 Feb, 23(2), 248 - 51 Susceptibility of Nocardia asteroides to 46 antibiotics, including 22 beta-lactams; Gutmann L et al.; Twelve Nocardia asteroides isolates were tested for their susceptibility to 46 antibiotics by the agar dilution method . N-Formimidoyl thienamycin was the most active of 22 beta-lactam antibiotics, inhibiting 11 of the 12 strains at 1 microgram/ml . Penicillins, including ureidopenicillins, showed poor activity . Cefotaxime, ceftriaxone, and especially cefuroxime had the best activities of the cephalosporins tested . Among the other antibiotics, amikacin and minocycline, respectively, inhibited all of the strains tested at 0.5 and 4 micrograms/ml. Surg Gynecol Obstet, 1983 Feb, 156(2), 212 - 6 The value of prophylactic antibiotics for simple lacerations; Thirlby RC et al.; A prospective study was undertaken to review the efficacy of antibiotics in the treatment of patients with minor lacerations . Four hundred and ninety-nine patients were randomized into two groups . Two hundred and twenty-seven patients in group 1 received cephalexin, 250 milligrams, every six hours for 72 hours . Two hundred and seventy-two patients in group 2 received no antibiotics . The over-all infection rate was 6.6 per cent, 33 of 499 patients . Sixteen of the 227 patients in group 1, 7.0 per cent, had infections develop compared with 17 of the 272 patients in group 2, 6.25 per cent . Seven of 51 patients, 13.7 per cent, in group 1 and three of 53, 5.7 per cent, in group 2 with mildly contaminated wounds had infections develop . No significant difference was noted between the groups according to the age of the patient, interval since injury, anatomic location or suture technique . Prophylactic, orally administered antibiotics do not decrease the incidence of infection in patients with suture closure of simple lacerations. Monatsschr Kinderheilkd, 1983 Feb, 131(2), 58 - 62 {Pharmacokinetics of combined antibiotic therapy in the newborn infant}; Heimann G et al.; In 66 newborn infants (AGA) suffering from septicemia concentration time courses of gentamicin, ampicillin and cefotaxim were determined to perform and an individual drug monitoring . Gentamicin was analysed from capillar blood samples using EMIT, Ampicillin and Cefotaxim by HPLC-technique . Volumes of distribution, apparent elimination half lives, maximum -, minimum and steady state concentrations were calculated using digital iteration programs . Based on a fixed dose regimen the kinetic parameters of gentamicin were extremely variable . To achieve a median steady state concentration of 3 micrograms/ml gentamicin in serum corrections from -17% to +110% of the foregoing dose were necessary . With 100 mg/kg ampicillin or cefotaxim per day sufficient concentrations in serum were reached . But in some patients a dosage of 5-7 mg/kg/d of gentamicin is too low, while others show concentrations near to the toxic levels . By a combination of gentamicin plus ampicillin pharmacokinetic parameters are not influenced; while if gentamicin is combined with cefotaxim the apparent elimination halflife of gentamicin (beta-slope) is significantly reduced . Therefore an individual drug monitoring of drugs with a small therapeutic range, for example gentamicin, is necessary to optimize therapeutic results. Cancer Res, 1983 Feb, 43(2), 460 - 72 Effect of anthracycline antibiotics on oxygen radical formation in rat heart; Doroshow JH; This investigation examined the effect of the anthracycline antitumor agents on reactive oxygen metabolism in rat heart . Oxygen radical production by doxorubicin, daunorubicin, and various anthracycline analogues was determined in heart homogenate, sarcoplasmic reticulum, mitochondria, and cytosol, the major sites of cardiac damage by the anthracycline drugs . Superoxide production in heart sarcosomes was significantly increased by anthracycline treatment; for doxorubicin, the reaction appeared to follow saturation kinetics with an apparent Km of 112.62 microM, required NADPH as cofactor, was accompanied by the accumulation of hydrogen peroxide, and probably resulted from the transfer of electrons to molecular oxygen by the doxorubicin semiquinone after reduction of the drug by sarcosomal NADPH:cytochrome P-450 reductase (NADPH:ferricytochrome oxidoreductase, EC 1.6.2.4) . Superoxide formation was also significantly enhanced by the anthracycline antibiotics in the mitochondrial fraction . Doxorubicin stimulated mitochondrial superoxide formation in a dose-dependent manner that also appeared to follow saturation kinetics (apparent Km of 454.55 microM); however, drug-related superoxide production by mitochondria required NADH rather than NADPH and was significantly increased in the presence of rotenone, which suggested that the proximal portion of the mitochondrial NADH dehydrogenase complex {NADH:(acceptor) oxidoreductase, EC 1.6.99.3} was responsible for the reduction of doxorubicin at this site . In heart cytosol, anthracycline-induced superoxide formation and oxygen consumption required NADH and were significantly reduced by allopurinol, a potent inhibitor of xanthine oxidase (xanthine:oxygen oxidoreductase, EC 1.2.3.2) . Reactive oxygen production was detected in all of our studies despite the presence of both superoxide dismutase (superoxide:superoxide oxidoreductase, EC 1.15.1.1) and glutathione peroxidase (glutathione:hydrogen peroxide oxidoreductase, EC 1.11.1.9) in each cardiac fraction . These results suggest that free radical formation by the anthracycline antitumor agents, which occurs in the same myocardial compartments that are subject to drug-induced tissue injury, may damage the heart by exceeding the oxygen radical detoxifying capacity of cardiac mitochondria and sarcoplasmic reticulum. J Pediatr Surg, 1983 Feb, 18(1), 42 - 6 Antibiotic excretion into the bile after hepatic-portojejunostomy in biliary atresia; Miyano T et al.; Antibiotic excretion into the bile was studied using LMOX and CMZ in 16 postoperative cases of biliary atresia patients who had had hepatic portoenterostomy with Suruga II type enterostomy with the following results: Group I: Excellent excretion which was almost the same as that seen with adult patients; Group IIa: Good or poor excretion, depending on the amount of bile flow and liver function; Group IIb: Very poor excretion; Group III: Good excretion but depending on the amount of bile flow and liver function . As the total bile acid level in bile showed a higher level, the biliary excretion of antibiotics was greater . Our study indicates that antibiotic excretion into the bile in infants is closely related to the condition of the liver function and the biliary passages. Am J Obstet Gynecol, 1983 Jan 15, 145(2), 239 - 44 Efficacy of antibiotic therapy in preventing spontaneous pregnancy loss among couples colonized with genital mycoplasmas; Quinn PA et al.; Evidence suggests that genital mycoplasmas play a role in spontaneous abortion, prematurity, and perinatal morbidity and mortality rate . Since these organisms are sensitive to antibiotics, three treatment regimens were assessed for efficacy in preventing spontaneous pregnancy loss . The pregnancy loss rate was significantly reduced from 96% to 47.4% among those treated with doxycycline prior to conception and to less than 20% among those treated with erythromycin stearate only during pregnancy or with both regimens . The reduction in pregnancy loss rate was independent of maternal age, the number of previous abortions, gestational age at abortion, or other minor abnormalities . Diagnosis and treatment of mycoplasma infection following a first or later pregnancy loss equally prevented spontaneous loss in the next pregnancy . These observations suggest that appropriate treatment of mycoplasma infection could also prevent recurrent spontaneous abortion syndrome in couples with positive cultures. J Biol Chem, 1983 Jan 10, 258(1), 183 - 91 Primary structure of macromomycin, an antitumor antibiotic protein; Samy TS et al.; The antitumor protein macromomycin is a single chain polypeptide of 112 amino acid residues cross-linked by two intramolecular disulfide bonds . The protein was reduced and S-alkylated with 2-mercaptoethanol in 8 M urea followed by treatment with iodoacetic acid . Tryptic digestion of tetra-S-carboxymethyl macromomycin gave four tryptic peptides which were fractionated by gel permeation on Sephadex G-50 . The amino acid sequence of the tryptic peptides and the overlap sequences were determined by a combination of automated Edman degradation analysis, gas chromatographic mass spectrometry, and fast atom bombardment mass spectrometry . A comparison of the structures of macromomycin, actinoxanthin, and neocarzinostatin suggests that they belong to a family of related proteins. Hum Genet, 1983, 64(3), 249 - 53 Reduced frequency of baseline sister chromatid exchanges in lymphocytes grown in antibiotics and serum-excluded culture medium; Das BC et al.; Peripheral venous blood from man, muntjac, and cattle were grown in medium (1) containing different serum (human AB+/FCS/autologous), (2) without serum or antibiotics (penicillin and streptomycin), or (3) without both serum and antibiotics to investigate to what extent certain essential culture components used in in vitro mammalian cell cultures affect the incidence of spontaneous sister chromatid exchanges (SCEs) . The observation that exclusion of only serum from culture medium enhanced the frequency of SCEs whereas exclusion of both serum and antibiotics, which influence the cell cycle kinetics to a great extent, exhibited the lowest frequency of SCEs reported so far for lymphocyte cultures, indicates that the frequency of so-called spontaneous SCEs usually observed in normal lymphocyte cultures grown in medium supplemented with serum and antibiotics is in fact an elevated frequency. Childs Brain, 1983, 10(4), 251 - 65 Brain abscess in childhood . A study of 34 cases treated by puncture and antibiotics; Hirsch JF et al.; During the last 15 years, 34 children were treated for a brain abscess . 13 (38%) had cyanotic heart disease; 12 (35%) had an ENT infection . The standardized treatment protocol included puncture of the abscess and administration of antibiotic and antiedematous drugs . Postoperative permanent epidural monitoring of intracranial pressure and, in the last 5 years, repeated CT scans indicated if retapping the abscess or reinforcing the antiedematous treatment was necessary . In 7 out of these 34 cases the abscess had to be excised . Postoperative mortality rate was 6% . Overall mortality rate was 12% . Neurological sequelae were slight . Epilepsy frequency was 10% . Mental retardation (18%) was found only in cyanotic congenital heart disease to which it is related . Repeated CT scans demonstrated the progressive disappearance of the capsule within a few months . This study shows an improvement in the results when brain abscesses in children are punctured rather than excised. Mol Pharmacol, 1983 Jan, 23(1), 127 - 32 Conformations of fortimicins and three-dimensional structure-activity relationship in the aminoglycoside antibiotics; Hirayama N et al.; The fortimicins are pseudodisaccharide antibiotics consisting of purpurosamine and fortamine moieties which are connected through an alpha-linkage . NMR spectra indicate that the fortamine ring in fortimicin A takes a chair conformation which corresponds to an inverted one in the conformation of fortimicin B free base . Fortimicin A is unstable in solution, and we were unable to obtain any crystals of it . To elucidate the structure of fortimicin A and to clarify the stereochemistry of fortimicins, we have undertaken to calculate their empirical force-fields starting from the X-ray structures of fortamines and fortimicin B free base . Nuclear Overhauser enhancement data were also employed to confirm the calculated relative orientation of the two rings around the glycosidic linkage . The 3-dimensional structure-activity relationship of aminoglycoside antibiotics is discussed on the basis of these results. Drug Chem Toxicol, 1983, 6(1), 21 - 40 The toxicologic evaluation of marcellomycin--an antineoplastic anthracycline antibiotic; Buroker RA et al.; Dose-related toxicologic effects of marcellomycin, an antineoplastic anthracycline antibiotic, were observed in single-dose studies in mice iv (43.05-67.65 mg/m2) and dogs iv (41.0-90.2 mg/m2), and in multiple-dose studies in dogs iv (9.8-29.6 mg/m2 2X/week for 6 weeks) and rats sc (9 weekly doses at 26.2-72.2 mg/m2) . Toxicity was primarily manifested by suppression of myeloid tissue, especially the erythrocytic and thrombocytic series, and lymphoid tissues . Initially a neutrophilic leukocytosis was observed in dogs and rats, which was considered possibly to be due to mobilization of the marginal and bone marrow neutrophil pools . In dogs, this was followed by a marked, dose-related neutropenia; and, in rats that died, there was marked depletion of bone marrow cells . Other toxicities observed included enteropathy, severe subcutaneous serofibrinous inflammatory edema and necrosis at injection sites, prostate and seminal vesicle atrophy, uterine hypoplasia, testicular and pancreatic degeneration, thyroid follicular proliferation and hemorrhage in various organs . In general, these toxicities were reversible in surviving animals during recovery periods . Significant cardiotoxicity was not demonstrated. Surgery, 1983 Jan, 93(1 Pt 2), 204 - 8 Prophylactic antibiotics in elective colon surgery; Bell GA et al.; A double-blind, randomized, prospective study comparing the efficacy of two intravenously administered antibiotics was conducted at Vancouver General Hospital on 98 patients undergoing elective colon surgery . The test drugs, erythromycin gluceptate and metronidazole, were each administered intravenously in 500 mg doses . The first dose was administered with the premedication 1 hour before surgery and the subsequent two doses were administered at 8-hour intervals . All patients received three doses of tobramycin intravenously, 1.5 mg/kg body weight, at the same time as the study drug . Fourteen patients developed wound infections, of which seven were classified as major and seven as minor infections . A major infection was diagnosed when the patient had a fever, required antibiotics, or had a prolonged hospital stay because of the wound infection . Three patients with major infections had received metronidazole and four had received erythromycin . Four patients with minor infections had received metronidazole and three patients had received erythromycin . The two treatment populations were similar with respect to type of surgery, age, gender, weight, and nutritional status . Both drugs were equally well tolerated . The overall wound infection was 14.4%, with no difference between erythromycin and metronidazole. Antibiotiki, 1983 Jan, 28(1), 15 - 8 {Auxotrophic mutants of the producer of the antibiotic mycoheptin Streptoverticillium mycoheptinicum}; Lapina IK et al.; The lethal and mutagenic effects of N-nitrozo-N-methyl biuret (NMB), N-nitrozo-N-methyl urea (NMU) and UV light on Streptoverticillium mycoheptinicum, strains O883 and 852, were studied . The concentrations of NMB were 0.005, 0.1 and 0.25 per cent, the exposure time was 2, 4 and 6 hours . The concentration of NMU was 1 per cent and the exposure time was 1, 2, 3, 4 and 5 hours . The dose of UV light was 2000 erg/mm2 . When the spores of Streptoverticillium mycoheptinicum, strain O883, were treated with NMB, the frequency of auxotrophic mutants increased from 0.63 to 3.4 per cent with an increase of the mutagen concentration from 0.05 to 0.25 per cent and the exposure time from 2 to 6 hours . More than 80 auxotrophic mutants were selected . When Streptoverticillium mycoheptinicum, strain 852, was treated with NMU, the frequency of auxotrophic mutants ranged from 0.5 to 2.4 per cent . Fifty-seven auxotrophic mutants were selected . The majority of the auxotrophic mutants selected with the use of NMB and NMU was unstable . Exposure of Streptoverticillium mycoheptinicum, strains 852, 10/69 Met and 54/100 Lys to UV light resulted in formation of groups of polyauxotrophic mutants. Arzneimittelforschung, 1983, 33(10), 1473 - 4 Effects of two new aminoglycoside antibiotics on the rat sciatic nerve-gastrocnemius muscle preparation; Renna G et al.; 2'-Amino-2'-deoxy-kanamycin (bekanamycin, Kanendomycin) and pentisomicin displayed a neuromuscular blocking activity on the rat sciatic nerve-gastrocnemius muscle preparation . Pentisomicin showed the highest neuromuscular blocking effect; the neuromuscular blocking potency of bekanamycin was similar to that of tobramycin, another new aminoglycoside . The neuromuscular block produced by these antibiotics was reversed by calcium chloride whereas it was not influenced by neostigmine methylsulfate. Bilt Hematol Transfuz, 1983, 11(2-3), 51 - 7 {Cardiotoxic effect of anthracycline antibiotics}; Jovanovic I et al.; Anthracycline antibiotic (Rubidomycin and Adriamycin) are often used for treatment of acute leukemia and variety of solid tumors . The use of greater doses of these agents is mostly limited by the damage of the cardiac muscle and by heart failure . The Rubidomycin cardiac toxicity analysis of children with acute leukemia has been considered in this paper . The results were obtained by investigating 53 patients who received this drug . They were classified in subgroups in relation to the total dose administered . Acute or chronic myocardial damage appeared in 6 children . The subgroup incidence of damage is directly proportional to the total dose administered. J Antibiot (Tokyo), 1983 Jan, 36(1), 30 - 5 Terminal steps in the biosynthesis of herbicidins, nucleoside antibiotics; Yoshikawa H et al.; The biosynthetic relationship of the herbicidins produced by Streptomyces saganonensis was studied with blocked mutants by means of a bioconversion method using growing and resting cells . It is proposed that the biosynthetic sequence for herbicidins is; herbicidin G----herbicidin F----herbicidin A . Both herbicidins A and F were converted to herbicidin B by non-enzymatic reactions . Herbicidin G was also converted to herbicidin C non-enzymatically. Arch Geschwulstforsch, 1983, 53(5), 429 - 39 {Cardiotoxic and myelosuppressive activity of various antitumor antibiotics of the anthracycline type in the rat}; Hoffmann H et al.; The cardiotoxic and myelosuppressive effects of the potential antitumor antibiotics violamycin BI (VBI) and violamycin BII (VBII) were studied in rats in comparison with daunorubicin (DAU), doxorubicin (ADR) and carminomycin (CAR) . Rats were intravenously given the compounds 10 times for three weeks at total doses of 0.4 to 3 times of the acute LD50 . Cardiac toxicity was measured using ECG (widening of the QRS complex), and screening parameters for bone marrow suppression were white blood cell counts, hematocrit and hemoglobin values . Following the drug injections the myocardium and the bone marrow were additionally investigated by light microscopy . With the exception of ADR, all the anthracyclines tested showed a more or less strong dissociation of cardiotoxic and myelotoxic activities . VBI was found to be only toxic on the heart but not on the bone marrow, whereas DAU, VBII and CAR were predominantly toxic on the bone marrow . Only ADR showed strong cardiac toxicity as well as distinct myelosuppression . A final evaluation of VBI and VBII has to include both the antineoplastic and the toxic properties of the compounds. Z Exp Chir Transplant Kunstliche Organe, 1983, 16(5), 306 - 14 {Model studies of the antibiotic release of gentamycin, tobramycin and cephalothin polymethylmethacrylate beads in vivo}; Laky R et al.; Gentamycin-, tobramycin-, and cephalothin-polymethylmethacrylat beads were implanted into a bone cavity of the rabbit tibia . The antibiotic release of the implants was observed by measure of the antibiotic concentration of the secretion respectively of the neighbouring bone tissue in the surroundings of the beads produced by punction . An antibiotic concentration about 1 microgram/ml could be measured with gentamycin and tobramycin for 120 to 150 days and with cephalothin for 30 to 50 days in the surroundings of the beads. Langenbecks Arch Chir, 1983, 360(3), 193 - 206 {Release delay of various antibiotics from resorbable tricalcium phosphate ceramic granules with soluble coating for local treatment of osteomyelitis . An animal experiment study}; Eitenmuller J et al.; The releasing kinetic of antibiotics from tricalcium phosphate beads was studied in animal experiments . The porous TCP-beads were filled with antibiotics and coated with biodegradable substances for delaying the release of the antibiotics . There were high tissue levels of antibiotics in the surrounding bone for many days . This method gains an increase in therapeutic safety in treatment of osteomyelitis . The coated TCP-antibiotic beads are used simultaneously as bone graft and for treatment of the bone infection . There is no need for further operation. Folia Microbiol (Praha), 1983, 28(5), 397 - 405 Determination of optimum conditions for antibiotic production by Streptomyces galbus; Paul AK et al.; The nutritional requirements and cultural conditions for optimal production of a new extracellular antifungal antibiotic by Streptomyces galbus under laboratory conditions were determined . Glycerol and glucose were found to be the best carbon sources, while as N-source nitrate was preferred . Maximum titre was reached after 7 d of incubation at 30 degrees C at pH 6.8 The metal ions Cu2+, Zn2+, and Fe2+ had some promoting effect . Casein hydrolysate improved production, but yeast extract markedly inhibited . Growth in shake flasks favoured higher yield of the antibiotic in a shorter time. Z Parasitenkd, 1983, 69(4), 457 - 71 The action of polyether ionophorous antibiotics (monensin, salinomycin, lasalocid) on developmental stages of Eimeria tenella (Coccidia, Sporozoa) in vivo and in vitro: study by light and electron microscopy; Mehlhorn H et al.; The effect of three polyether antibiotics (monensin, salinomycin, lasalocid) on developmental stages of Eimeria tenella (Coccidia, Sporozoa) was studied in vivo and in vitro by means of light and electron microscopy . It was found that these three drugs act against free merozoites, which are destroyed by bursting of the cell border (i.e . pellicle), endoplasmic reticulum and internal organelles even after very short exposure times (20 min) in media containing 1 ppm, 10 ppm or 100 ppm of these drugs . Sporozoites, however, survived these drug concentrations during an exposure time of 30 min (this would be sufficient to penetrate host cells and start development) . Intracellular stages, which were situated in a parasitophorous vacuole within an intact host cell, were not attacked, apparently because these drugs are almost incapable of penetrating host cells . On the other hand, parasites (such as differentiated schizonts, gamonts) located within degenerating host cells showed slight disintegration, which did not necessarily led to their death . From these results it becomes clear why these polyether antibiotics have to be fed daily . Doses of 70 ppm salinomycin, 125 ppm monensin and 125 ppm lasalocid were found to bring about an equivalent protective effect against an infection with 40,000 Eimeria tenella oocysts. Int J Tissue React, 1983, 5(2), 181 - 6 Toxic effects of some antibiotics on rabbit kidney cells; Viano I et al.; The cellular toxicity of some antibiotics (cephaloridine, cefazolin, cefoperazone and gentamicin) was studied in vitro using rabbit kidney cell cultures . In order to evaluate the importance of the different factors causing toxic effects, the authors studied the correlations between toxicity and antibiotic concentration and between toxicity and period of contact . The toxic effects were measured by LDH release and by neutral red uptake inhibition . In both tests, gentamicin clearly showed curvilinear dose-toxicity and time-toxicity correlation but the cephalosporins did not do so in either test . However the antibiotics tested all showed various degrees of toxicity, suggesting that their specific toxic activity on renal cells was greater than that of aspecific variables linked to pharmacokinetic behaviour. Folia Microbiol (Praha), 1983, 28(4), 282 - 6 Biological properties of acmycin, a new polyene antibiotic; Chakrabarti S et al.; Acmycin, a new polyene antibiotic, was fungistatic at low and fungicidal at high concentrations . It produced malformations in conidia of Helminthosporium oryzae and Curvularia lunata and caused leakage of yeast cells . Acmycin was fairly nontoxic to germinating seeds . The intravenous LD50 was 300-400 and intraperitoneal maximum tolerated dose 100-500 mg/kg body mass of mice. Clin Ther, 1983, 5(5), 488 - 94 Evaluation of cochlear toxicity of aminoglycoside antibiotics in guinea pigs by scanning electron microscopy; Sato K; The cochlear toxicities of six aminoglycoside antibiotics were functionally and morphologically evaluated in guinea pigs . Forty-six Hartley strain guinea pigs were allocated into seven groups, including a control, and given intramuscular injections of one of the drugs or saline solution daily for 28 days . The hearing thresholds of all the animals were measured by the differential frequency pinna reflex test before, during, and after treatment to assess changes in cochlear function . Scanning electron microscopy was used to examine morphological changes in the cochlea after treatment and to detect degenerative changes in the auditory hairs of the basal turn . The results obtained from the functional and morphological examinations were well correlated, indicating the most severe changes in animals given gentamicin followed, in order, by amikacin, tobramycin, kanamycin, dibekacin, and ribostamycin. Pharmacology, 1983, 27(5), 255 - 66 Antiarrhythmic and cardiovascular actions of the new antibiotic agent pirlimycin adenylate; Kopia GA et al.; Pirlimycin adenylate (U-63,440) is a clindamycin analog possessing antiarrhythmic activity . In the anesthetized dog, the sustained ventricular tachycardia produced by ouabain intoxication is converted to a normal sinus rhythm with an average dose of 26.0 +/- 5.1 mg/kg of pirlimycin adenylate (range 13.4-40.7 mg/kg i.v.) . The drug failed, however, to decrease arrhythmia frequency in a modified 2-day Harris dog preparation even with doses of up to 100 mg/kg . The efficacy of pirlimycin adenylate against ouabain-induced arrhythmias cannot be ascribed to a local anesthetic action, since concentrations of up to 5 X 10(-3) M produced only a small (26 +/- 5%) reduction in the spike amplitude of desheathed isolated frog sciatic nerves . In contrast, lidocaine (5 X 10(-3) M) produced a 91% reduction in single spike amplitude . Neither did pirlimycin adenylate (up to 10(-3) M) produce any negative inotropic effect in isolated cat papillary muscles, while both lidocaine and quinidine were cardiodepressant at 10(-3) M . It is concluded that pirlimycin adenylate may be an interesting prototype antiarrhythmic agent and further chemical modification of the drug molecule might increase the spectrum of antiarrhythmic activity without altering the drug's toxicity. Ann Genet, 1983, 26(3), 147 - 9 {Fragility of the X chromosome and inhibition of dihydrofolate reductase . Comparison of the effects of 2 antibiotics: trimethoprim and pyrimethamine}; Calva-Mercado MP et al.; The increase in frequency of the Xq27 gap is investigated after addition to the culture medium of two inhibitors of dihydrofolate reductase : trimethoprim (TMP) and pyrimethamine (PMT) . Neither antibiotic induced the gap in ten normal subjects . In five Xqfra, mentally retarded, untreated boys, TMP (26,7 mg/l) and PMT (1,25 mg/l) increased equally the gap frequency . In two out of four women carrying the Xqfra and in three out of four Xfra mentally retarded boys, treated for a few months, with oral folic acid (one milligram/kg/day), TMP increased the frequency of the gap, while PMT was practically inactive . PMT is a much more powerful inhibitor of dihydrofolate reductase than TMP : it was concluded therefore that TMP could also act on some other steps of the monocarbons' metabolism . The only patient who reacted strongly to both TMP and PMT had previously suffered a severe neurologic regression during an antibiotherapy with TMP . It is stressed that dihydrofolate reductase inhibitors should be avoided when treating Xqfra patients. Postgrad Med J, 1983, 59 Suppl 3, 179 - 80 The use of antibiotics in acute-on-chronic bronchitis; Anderson G; Acute exacerbations of bronchitis are probably best treated with erythromycin or cotrimoxazole . The rising incidence of ampicillin resistance is reducing its value . Oxytetracycline and cephalosporins are best avoided . Trimethroprim may prove a safer alternative to cotrimoxazole . However, all these conclusions are based on theoretical reasons rather than large comparative trials. Biomaterials, 1983 Jan, 4(1), 29 - 32 In vitro properties of mixtures of fibrin seal and antibiotics; Redl H et al.; The incorporation of gentamycin, neomycin and Polymyxin E into fibrin seal results in prolonged clotting time after mixture with 4 NIH-units of thrombin per ml in vitro . The aminoglycoside antibiotics gentamycin and neomycin also diminished fibrin-alpha-chain crosslinkage and, as a consequence, clot rigidity, as demonstrated with clots containing gentamycin . Clotting time and the rate of alpha-chain crosslinking can be adjusted to normal values by the use of higher thrombin concentrations and incorporation of additional factor XIII into the sealing system . Drug release from the clots was similar for all three antibiotics tested and mainly dependent on the concentration gradient between the clot and its environment . Under the conditions of the present study, about 85% of the antibiotic content of fibrin seal clots were released within 72 h. Acta Otolaryngol Suppl, 1983, 405, 1 - 16 Comparative ototoxicity of four aminoglycosidic antibiotics during the critical period of cochlear development in the rat . A functional and structural study; Lenoir M et al.; The comparative ototoxicity of four aminoglycosides (amikacin, dibekacin, gentamicin and tobramycin) was evaluated in the rat during the critical period of cochlear development . Newborn rats received a daily subcutaneous injection of one of the four antibiotics for 8 consecutive days, starting on day 8 after birth (amikacin: 225 mg/kg, dibekacin: 60 mg/kg, gentamicin and tobramycin: 45 mg/kg) . Evaluation of ototoxicity was assessed one month after the end of the treatment using cochlear recordings (action potential and cochlear microphonic), surface preparations and scanning electron microscopy . No functional or structural evidence of ototoxicity was found in animals treated with dibekacin . Tobramycin had a weak ototoxic effect characterized by a slight increase in N1 latency and moderate damage to OHC stereocilia (fusion and formation of giant cilia) . Gentamicin-treated animals demonstrated more severe evidence of ototoxicity including increased thresholds for CM, and a higher incidence of missing hair cells and damage to OHC stereocilia . The maximal cochlear damage was observed in amikacin-treated animals: both AP and CM thresholds were severely impaired, cell counts and SEM showed extensive loss of hair cells. Biomed Biochim Acta, 1983, 42(7-8), 855 - 66 A mesophase (liquid crystal) state of DNA complexes with anthracycline antibiotics; Yevdokimov YuM et al.; In the presence of polyethyleneglycol water-salt solutions, DNA is condensed to a kind of mesophase (liquid crystals) . The peculiar properties of this phase caused by anisotropic orientations have been analyzed by circular dichroism (CD) of condensed particles of DNA complexed with dyes, i.e . anthracycline antibiotics (daunomycin, aclacinomycin A), actinomycin, and ethidium bromide . The anthracycline complexes show intense CD bands in the visible and the UV region . Daunomycin induces a typical reversal of the sign of these CD bands with increasing occupation of the double helix contrary to the other ligands . This characteristic effect and its partial reversal after removal of daunomycin from the condensed particles can be the result of the change of the direction of the mesophase helical twist owing to an energy change of interaction between DNA molecules, and partially to a modification of base-plane inclination (tilt), too . This new type of DNA complex state is characterized in detail. J Antimicrob Chemother, 1983 Jan, 11 Suppl, 179 - 83 Animal pharmacokinetics and toxicology of cefotetan--a new cephamycin antibiotic; Suzuki H et al.; In animal pharmacokinetic studies the biological half-lives of cefotetan were 13.0 min in mice, 15.9 min in rats, 30.5 min in rabbits, 55.5 min in dogs and 77.9 min in rhesus monkeys . The acute intravenous LD50 values (g/kg) were 6.4 and 5.0 in male and female mice, respectively, and 8.5 and 6.8 in male and female rats, respectively . Six-month repeated dose studies of 30 to 1000 mg/kg per day intraperitoneally in rats and 100 to 600 mg/kg per day intravenously in rhesus monkeys showed no notable organ toxicity . A teratogenicity study in rats indicated that cefotetan had no adverse effects on fetal and postnatal development . The nephrotoxicity of cefotetan in rabbits was considerably less than that of cefazolin. Psychopharmacology (Berl), 1983, 79(2-3), 108 - 10 Interference with human memory by an antibiotic; Idzikowski C et al.; Thirty-two volunteers learned a sentence after awakening from early in the first REM period of sleep and recalled it after awakening from the third REM period, under experimental conditions that controlled for state dependency . The tetracycline antibiotic doxycycline (200 mg), taken at bedtime, impaired recall possibly through a putative inhibitory action on brain protein synthesis. Int J Clin Pharmacol Res, 1983, 3(6), 449 - 58 Effects of macrolide antibiotics on drug metabolism in rats and in humans; Pessayre D; In rats, troleandomycin induces microsomal enzymes and promotes its own transformation into a metabolite forming an inactive complex with the iron (II) of cytochrome P-450; eventually, several monooxygenase activities are markedly reduced . In humans, troleandomycin also induces microsomal enzymes, and forms an inactive cytochrome P-450-troleandomycin metabolite complex; the clearance of antipyrine, that of theophylline, and that of methylprednisolone are markedly reduced . The concomitant administration of troleandomycin and other drugs may produce ischaemic accidents (ergotamine), cholestasis (oral contraceptives) and neurologic signs of intoxication (theophylline or carbamazepine) . Qualitatively similar effects are produced, in rats and in humans, by erythromycin . These effects, however, are much weaker than those of troleandomycin . In humans, the clearance of antipyrine and that of theophylline are only slightly affected . Drug interactions have been reported in a few patients only . Josamycin and midecamycin do not form cytochrome P-450-metabolite complexes in rats . In humans, these macrolides do not inhibit the clearance of theophylline; midecamycin does not inhibit the clearance of antipyrine . Although a case of possible josamycin-ergotamine interaction has been reported, the role of josamycin may be questioned in this isolated instance . Midecamycin, or josamycin, might be preferred to other macrolides in those patients who must receive other drugs metabolized by cytochrome P-450. Ann Dermatol Venereol, 1983, 110(12), 1007 - 10 {Role of corticoid-antibiotic combinations in local treatments . Critical study}; Revuz J et al.; Current literature about steroid antibiotic combinations has been critically reviewed . The use of such combinations may be considered in infected steroid sensitive dermatosis . Definition of super-infection is however impossible on clinical data only . A single study demonstrated the superiority of the combination upon the steroid alone in well defined experimental conditions . This superiority is not demonstrated beyond 8 days of treatment or in case of pretreatment with local antiseptic solutions or baths . Theoretical side effects of local antibiotics include, sensitization, selection of antibiotic resistant germs, systemic toxicity . They are not troublesome in current practice . However adjunctions of an antibiotic can diminish the steroid efficacy when infection is not present . The real usefulness of the combination in current practice is still to be demonstrated. Scand J Gastroenterol Suppl, 1983, 85, 74 - 82 Antibiotic-associated colitis; Froland SS; A survey is given of antibiotic-associated colitis (AAC) as a clinical problem . Current theories on the etiology and pathogenesis are briefly described . The approach to diagnosis and therapy is outlined. Mol Cell Biochem, 1983, 55(1), 17 - 40 The mechanism of action of quinone antibiotics; Lown JW; The review describes recent studies designed to elucidate the molecular mechanism of action of certain quinone antibiotics which exhibit or have potential for clinical treatment of malignant diseases . Although a large number of quinone antibiotics has been described the review will concentrate on four types, the anthracyclines, the mitomycins, streptonigrin, and the saframycin antibiotics because of their biological significance and because the understanding of their underlying modes of action is perhaps more advanced than in the case of other antibiotics . It will be evident that although the antibiotics bear a common quinone moiety this does not confer a commonality of mechanism . Indeed the variety and precision of the different chemical lesions induced by quinone antibiotics on nucleic acids, their principal cell targets, is remarkable . The particular lesions identified include (i) equilibrium binding, (ii) "permanent' single covalent attachment, (iii) reversible covalent binding, (iv) metal ion sequestration and subsequent DNA binding, (v) DNA groove and base specific binding, (v) interstrand cross-linking, (vi) intercalation with concomitant supercoil relaxation and duplex extension, (viii) redox cycling with production of reactive oxygen species and DNA single strand breaks, and (viii) single strand breaks as a result of phosphotriester formation . In many cases the chemical mechanisms involved in these individual processes may be elucidated in in vitro experiments on purified DNAs by the application of ethidium binding assays in conjunction with certain cellular repair enzymes and utilizing techniques including high field nuclear magnetic resonance and electron paramagnetic resonance spectroscopy . The data obtained in this way complement and extend information from cell culture and in vivo experiments . A coherent description of the multiple cellular effects of these reactive agents is emerging . Such reactions involve bioreductive activation of the quinone the subsequent course of which is precisely controlled by structural and stereochemical factors within the individual antibiotic . The concomitant chemical reactions on cellular macromolecules are beginning to be related to pharmacological properties including in the case of the anthracyclines, a plausible rationale for the molecular origin of the dose limiting cardiotoxicity. Adv Shock Res, 1983, 10, 195 - 215 Prevention or amelioration of morphologic lesions in LD100 E coli-shocked baboons with steroid/antibiotic therapy; Archer LT et al.; We have documented the effectiveness of methylprednisolone sodium succinate (MPSS) and gentamicin sulfate (GS) therapy for LD100 E coli-induced shock in the baboon . We sequentially delayed initiation of MPSS infusion from 30 to 120 min and then to 240 min after onset of a 2-h E coli infusion . Treatment resulted in 100%, 85%, and 65% survival respectively . In this study we evaluated tissue taken at autopsy in the three MPSS/GS treatment studies including untreated baboons and those treated with GS only . When animals died (3-49 h) or were sacrificed (7-71 days), tissues were removed, coded, and prepared for histopathologic evaluation by light microscopy . On the basis of morphologic changes animals split into two groups: baboons with little or no tissue alterations (survivors), and those with multiple organ damage (nonsurvivors) . Combinations of mild to massive congestion, edema, hemorrhage, fibrin thrombi, increased numbers of polymorphonuclear leukocytes (PMNs), and necrosis of the adrenal glands, liver, kidneys, lungs, and spleen of nonsurvivors were prevented or ameliorated in the MPSS/GS-treated surviving baboons . Data demonstrate the MPSS/GS therapy prevents or reverses the multiple organ damage and increases survival in lethal septic shock. Chemotherapy, 1983, 29(4), 244 - 8 Effect of ceftizoxime, a new cephalosporin antibiotic, on binding of bilirubin to human serum albumin; Sakamoto H et al.; An investigation and comparison of the competitive effect of ceftizoxime, a new cephalosporin, and other beta-lactam antibiotics on in vitro binding of bilirubin to human serum albumin showed that at a normal range of serum albumin (3.48 g/dl) and bilirubin (0.94 mg/dl) in healthy infants, free bilirubin did not increase in the presence of any of the test antibiotics at concentrations up to 640 micrograms/ml . When the albumin concentration was decreased to one-fifth of the normal human range, only ceftizoxime caused no bilirubin displacement. Arzneimittelforschung, 1983, 33(3), 423 - 6 {Use of hydroxyapatite for determination of antibiotic concentrations in bone}; Wittmann DH et al.; A new method to determine antibiotic bone concentrations is presented . The bone fragments, obtained during hip joint replacement operations in 10 patients were investigated for antibiotic activity after i.v . application of 2 g of oxacillin and 4 g of mezlocillin . We were able to show that both penicillins do not penetrate into the inorganic bone part (hydroxylapatite) . Therefore the concentrations measured are related to the organic bone part and are expressed in units per volume rather than in units per weight . With this method the differences between spongious and cancellous bone observed so far are diminished to values without any statistical difference . After 2 g of oxacillin and 4 g of mezlocillin the concentrations are 13.1 mg/l and 34.0 mg/l, respectively . The serum concentrations measured are compared to the bone concentrations . The terminal serum half-life is 63 min for oxacillin and 80 min for mezlocillin when the drugs are given simultaneously. Mol Pharmacol, 1983 Jan, 23(1), 8 - 16 The influence of antibiotics on agonist occupation and functional states of the nicotinic acetylcholine receptor; Brown RD et al.; Four distinct classes of antibiotics, the aminoglycosides, tetracyclines, lincomycin-clindamycin, and peptides, were examined in intact BC3H-1 cells for their capacity to influence the relationship between agonist binding to the cholinergic receptor and the response elicited . The most potent inhibitors were the peptides of the polymyxin-colistin class, which at submicromolar concentrations noncompetitively blocked agonist-elicited Na+ permeability . These agents at equivalent concentrations also enhanced the apparent affinity of agonists for the receptor . Comparisons of agonist occupation of the receptor and agonist promotion of desensitization showed that the noncompetitive inhibition by peptide antibiotics occurred largely by augmenting the conversion of the receptor to a high-affinity, desensitized state . Rates of receptor desensitization were also substantially enhanced in the presence of these antibiotics . Thus, an analysis of receptor occupation and response suggests that the polymyxin antibiotics act as heterotropic allosteric effectors by promoting the conversion of the cholinergic receptor to its desensitized state . By contrast, the other antibiotics studied inhibited permeability at far higher concentrations . Although a noncompetitive component of inhibition could be identified with certain antibiotics such as neomycin, they did not appear to enhance agonist affinity . Thus, the various antibiotics differ substantially in their potencies and basic mechanisms of inhibition of the acetylcholine receptor. Ann Ophthalmol, 1983 Jan, 15(1), 24 - 8 Use of steroid/antibiotic prophylaxis in intraocular lens implantation: a double-masked study v placebo; Stewart RH et al.; A prospective, randomized, double-masked study was conducted to compare the efficacy of steroid/antibiotic treatment to placebo in reducing postoperative ocular inflammation . Patients undergoing planned extracapsular cataract extraction with intraocular lens implantation were treated with either placebo or a combination product containing dexamethasone, neomycin, and polymyxin B for three days prior to surgery and three weeks following surgery . Five of thirteen (38%) patients treated with placebo developed significant iritis postoperatively, while none of ten (0%) patients treated with the combination product developed excessive inflammation (P = 0.027) . Two patients treated with the steroid/antibiotic combination product experienced a broken suture postoperatively followed by iris prolapse, as compared to none in the placebo group (P greater than 0.10) . More types and significant numbers of bacteria were isolated from the eyes of the placebo-treatment group after therapy than were found in the steroid/antibiotic-treatment group. Scand J Infect Dis, 1983, 15(1), 33 - 42 Epidemiology of gonorrhoea: serogroup, antibiotic susceptibility and auxotype patterns of consecutive gonococcal isolates from ten different areas of Sweden; Danielsson D et al.; Consecutively isolated gonococcal strains from 10 representative geographical areas in Sweden were serogrouped according to the previously described W antigen class . The majority of the strains were antibiotic susceptibility tested and approximately one fourth of them were auxotyped . Statistically significant differences of the serogroup patterns were demonstrated between the 2 largest towns, which represented highly urbanized areas where serogroup W II dominated, and the middle sized towns with adjoining rural districts, where serogroup W I dominated . The serogroup patterns of the strains isolated in 3 university towns were representative for Sweden as a whole . Statistically significant differences were demonstrated between urban and rural areas with regard to the susceptibility of gonococci to beta-lactam antibiotics . About 95% of serogroup W I strains were highly sensitive to ampicillin whereas about 65% and 90% of W II and W III strains, respectively, showed decreased susceptibility . The majority of the auxotyped strains belonged to 4 main types: Pro-, Pro-Arg-Ura-, AHU- and prototrophic . The majority of the AHU- strains belonged to serogroup W I and were highly susceptible to beta-lactam antibiotics and tetracycline . Many of the Pro-Arg-Ura-strains belonged to 2 particular subserogroups within serogroup W II and showed increased resistance to beta-lactam antibiotics . Serological classification of gonococci by co-agglutination is a simple and rapid technique without need of special equipment . It could serve 2 purposes: 1) as a confirmation test for gonococci cultured from clinical specimens; 2) for serogrouping of gonococcal isolates to study the epidemiology of gonorrhoea with regard to geographical areas, race, sexual preference, treatment failure and other demographic and medical factors. Folia Haematol Int Mag Klin Morphol Blutforsch, 1983, 110(6), 879 - 86 Preparing platelet concentrates from banked blood stored for 1-5 days by using tetracycline antibiotics; Agranenko VA et al.; It was shown that storage of banked blood up to five days did not change number of platelets and their functional integrity was retained rather well . That made possible the development of a method for preparation of viable platelet concentrates (PC) from stored blood . This method is based on the reversibility of the tetracycline antibiotics inhibitory effect on platelet activation process . According to the results of our in vitro studies PC from stored blood seem to be suitable for clinical usage . This tetracycline method of PC preparation from stored blood may provide a more efficient utilization of available donor blood to meet the ever-expanding needs for PC transfusions. J Pharm Pharmacol, 1983 Jan, 35(1), 19 - 22 Moment analysis for disposition kinetics of several cephalosporin antibiotics in rats; Yamaoka K et al.; Disposition kinetics of cefamandole, cefoperazone, cefotiam, cefmenoxime and cefmetazole following rapid intravenous injection into rats is investigated . The plasma concentrations of the antibiotics are determined by the high performance liquid chromatographic method, and the pharmacokinetic behaviours of the cephalosporins are evaluated by moment analysis which is a model-independent method . Analysis of variance (ANOVA) followed by the paired t-test reveals that cefmetazole and cefmenoxime have greater mean residence time (MRT) than cefotiam, cefamandole and cefoperazone, and that cefamandole and cefmetazole show larger steady-state volume of distribution (Vss) than the other cephalosporins . Cefamandole has the greatest total body clearance (40.2 ml kg-1 min-1) and cefmenoxime the smallest (7.72 ml kg-1 min-1). Biochim Biophys Acta, 1982 Dec 31, 699(3), 211 - 6 Differential inhibition of a restriction enzyme by quinoxaline antibiotics; Malcolm AD et al.; The inhibition of cleavage by HpaI at two well-defined restriction sites in linearised phi X174-RF DNA by quinoxaline antibiotics has been investigated . Echinomycin, which displays a certain preference for binding to GC basepairs, inhibits cleavage at one site much more than the other, whereas triostin A, which displays less pronounced sequence-selectivity, inhibits both sites about equally . Other congeners inhibit reaction at the two sites with varying effectiveness . The results demonstrate the usefulness of studying inhibition of cleavage at specific sites by restriction enzymes as a means of exploring the specificity of DNA-ligand interactions. Ital J Orthop Traumatol, 1982 Dec, 8(4), 461 - 7 The mechanical properties of "cement-antibiotic" mixtures; De Palma L et al.; The authors investigated the mechanical properties of "CMW cement-antibiotic" mixtures compared with those of the standard preparation . They carried out comparative tests of tensile strength, hardness and flexion (flexion breaking load, percentage flexion, modulus of elasticity to flexion) . The antibiotics used were: streptomycin, ampicillin, cefalotin, carbenicillin, rifampicin, kanamycin, gentamycin and tobramycin . The mechanical tests performed showed that the percentage reductions in the strength of the mixtures varied considerably depending on the type of antibiotic used . The reductions produced by antibiotics used in aqueous solution (gentamycin and tobramycin) were excessive . The results obtained with the other mixtures were much better; in particular, some of the values obtained with the CMW cement-cefalotin and CMW cement-streptomycin mixtures were very close to those for the standard preparation . The combination of rifampicin with CMW cement, on the other hand, prevented complete polymerization of the cement. Antibiotiki, 1982 Dec, 27(12), 42 - 6 {Effect of polyene antibiotics on the development of alcoholic-dietary fatty degeneration of the liver in rats}; Titov AV et al.; The effect of the sodium salts of levorin, isolevorin, nystatin and amphotericin B prepared with the use of sodium desoxycholate and amphoglucamine on the development of fatty degeneration of the liver was studied in rats . Fatty degeneration of the liver was induced in the animals by the diet deficient in choline and administration of alcohol (10 g/kg) . Most of the studied antibiotics inhibited the development of the liver fatty degeneration . The only exclusion was amphotericin B prepared with the use of sodium desoxycholate which did not influence the level of the liver fatty degeneration . Sodium levorin (10 mg/kg) produced the most pronounced normalizing effect on the lipid metabolism in the liver . Complication of mycoses with fatty degeneration of the liver should not be considered as a contraindication to their treatment with polyenic antibiotics. Biochem Pharmacol, 1982 Dec 1, 31(23), 3769 - 73 An interaction of aminoglycoside antibiotics with Ca binding to lipid monolayers and to biomembranes; Lullmann H et al.; Thirteen aminoglycoside antibiotics were investigated with respect to their ability to replace Ca from phosphatidylserine monolayers . The affinities of the glycosides for the Ca-binding sites depended on the pH and the Ca2+ concentration of the aqueous subphase . At a Ca2+ concentration of 1.2 X 10(-5)M and a pH of 7.5 the half maximum concentrations to replace Ca were found to range from 0.4 X 10(-6) (sisomicin) to 6 X 10(-6)M (streptomycin) . The interaction between the streptomycins and Ca were of a competitive nature, whereas the aminoglycoside antibiotics with higher affinities displayed unusual steep dose-response curves suggesting positive cooperativity . The aminoglycoside antibiotics were also able to replace Ca from biomembranes (red cell ghosts and isolated sarcolemma of cardiac muscle) in a dose-dependent manner . The high affinity of aminoglycoside antibiotics to a phospholipid is considered to be involved in the toxic side effects of these antibiotics, e.g . nephrotoxicity and impairment of contractile force. Antimicrob Agents Chemother, 1982 Dec, 22(6), 1017 - 21 Comparative pharmacokinetics of aminoglycoside antibiotics in guinea pigs; Chung M et al.; The pharmacokinetics of netilmicin, gentamicin, and tobramycin in plasma and in perilymph of guinea pigs were studied after a single intravenous injection of 40 mg/kg . Detailed pharmacokinetic analysis of the plasma drug concentration-time data up to 36 h after the intravenous dose revealed that the pharmacokinetics of the aminoglycoside antibiotics can be best described as a three-compartment open model . The disposition half-lives (t1/2) in plasma of the three antibiotics were comparable and within the following ranges: t1/2 alpha of 0.09 to 0.16 h; t1/2 beta of 0.88 to 1.01 h; and t1/2 gamma of 7.87 to 8.29 h . The volume of distribution in the central compartment and the total body clearance of netilmicin (294 ml/kg, 5.74 ml/min per kg) were greater than those of gentamicin (160 ml/kg, 3.40 ml/min per kg) and tobramycin (204 ml/kg, 4.63 ml/min per kg) . Pharmacokinetic analysis of the perilymph drug concentration-time data indicated that all three antibiotics penetrated the perilymph readily, but netilmicin cleared from the perilymph compartment faster than gentamicin and tobramycin . The maximum perilymph drug concentrations were 4.17, 8.05, and 6.78 micrograms/ml and occurred at 1, 2, and 4 h for netilmicin, gentamicin, and tobramycin, respectively . The ratio of area under the curve of perilymph to plasma was lowest for netilmicin (0.27), followed by gentamicin (0.39) and tobramycin (0.57) . These results suggest that the differences in pharmacokinetics and concentrations of netilmicin in the perilymph may account for less ototoxic liability of netilmicin compared with gentamicin and tobramycin. J Pharm Sci, 1982 Dec, 71(12), 1313 - 8 Effects of surfactants on the aqueous stability and solubility of beta-lactam antibiotics; Tsuji A et al.; Studies were undertaken to elucidate the interaction between beta-lactam antibiotics and surfactant micelles and to examine the effects of surfactants on their aqueous stability and solubility . The apparent binding constant of the micelle-antibiotic complex was determined as a function of the solution pH at 37 degrees and mu = 0.15 by the dynamic dialysis method and hydrolysis study . In the interaction with nonionic and anionic micelles of polyoxyethylene-23-lauryl ether (I) and sodium lauryl sulfate (II), large differences were noted in the binding constants between the undissociated and ionized species of penicillins . However, the cationic surfactants, cetyltrimethylammonium bromide (III), showed no significant difference in the binding constants for both species . Acid degradation of penicillins was protected in micellar solutions of I and III but was facilitated in micelles of II . The surfactants exerted no influence on the neutral degradation of the antibiotics used . The solubilization of penicillin V acid by micelles of I was studied at pH 2.0 and 35 degrees . The solubility increased threefold in the presence of 10 mM I. Drug Intell Clin Pharm, 1982 Dec, 16(12), 935 - 8 The influence of dose frequency and agent toxicity on the cost of parenteral antibiotic therapy; Rapp RP et al.; The influence of the number of daily doses on the overall cost of antibiotic therapy is examined in a general surgery patient population . Patients receiving a single first-generation cephalosporin are compared with patients receiving two or three antibiotics (including an aminoglycoside) in terms of (1) the cost of the drug and the supplies, (2) time required for nursing and pharmacy personnel to prepare and administer the doses, and (3) the influence of agent toxicity (renal function) on physician-ordered laboratory tests . On the whole, combination therapy including an aminoglycoside was four times as expensive as single-agent (first-generation cephalosporin) therapy . If future studies demonstrate that single-agent antibiotic therapy is as effective as traditional combination therapy for specific infectious diseases, the influence of the number of daily doses of drug and agent toxicity may support the cost-effective use of the newer agents. Surgery, 1982 Dec, 92(6), 1068 - 71 Bioactive antibiotic levels in the human aorta; Mutch D et al.; A new bioassay was used to determine the level of active antibiotic within the aortic wall in 24 patients undergoing elective aortic surgery involving prosthetic grafts . The patients were divided into three groups and received either cefazolin, clindamycin, or cefoxitin intravenously at the induction of general anesthesia . Cefazolin and cefoxitin attained satisfactory tissue levels . Clindamycin did not reach therapeutic levels in the aortic wall . Blood levels did not correlate well with tissue levels. Surg Gynecol Obstet, 1982 Dec, 155(6), 801 - 3 The value of prophylactic antibiotic therapy during endoscopic retrograde cholangiopancreatography; Hershey SD et al.; Prophylactic antibiotics have been recommended during endoscopic retrograde cholangiopancreatography in the hope of preventing septic complications . However, their effectiveness has not been proved clinically . In this study, the ability of the pancreas to secrete ampicillin, gentamicin and clindamycin after a single intravenous dosage, given prior to endoscopic retrograde cholangiopancreatography in 12 patients, was examined . Simultaneously obtained serum antibiotic levels were within the expected therapeutic range . In contrast, pancreatic ductal levels of ampicillin and gentamicin were too low to be measured in most patients . Most patients had measurable clindamycin levels which ranged from 12.0 to 3.1 micrograms per milliliter in seven patients and was 8.0 micrograms per milliliter in one patient . Parenteral prophylactic antibiotic coverage for endoscopic retrograde cholangiopancreatography is ineffective with gentamicin or ampicillin . Clindamycin may be of value, but it needs further study at higher dosages. Gastroenterology, 1982 Dec, 83(6), 1259 - 60 Rectal sparing in antibiotic-associated pseudomembranous colitis: a prospective study; Tedesco FJ et al.; A prospective study of 22 patients with antibiotic-associated pseudomembranous colitis demonstrated that the most distal location of the pseudomembranes was noted from 0 to 25 cm from the anus in 17 patients, from 25 to 60 cm from the anus in 3 patients, and greater than 60 cm from the anus in only 2 patients . These data suggest that the pseudomembranes will be noted by the rigid sigmoidoscope in 77% of the patients and by the flexible sigmoidoscope in 91% of the patients . Colonoscopic examination beyond 60 cm from the anus was necessary for the diagnosis of pseudomembranous colitis in 2 (9%) patients. Antimicrob Agents Chemother, 1982 Dec, 22(6), 976 - 80 Radioimmunoassay for metabolites of 9,3"-diacetylmidecamycin, a macrolide antibiotic; Shimada N et al.; A radioimmunoassay system has been developed for the measurement of two major metabolites of 9,3"-diacetylmidecamycin, Mb-6 and Mb-12 . A radioimmunoassay for Mb-6 was performed by using anti-Mb-6 serum and a {125I}tyramined Mb-6 derivative as a radiolabeled antigen . The labeled antigen was prepared by the chloramine T method . The antiserum was obtained from a rabbit immunized with Mb-6 conjugated to bovine serum albumin . The obtained antiserum was cross-reactive with two other metabolites of 9,3"-diacetylmidecamycin, Mb-2 and Mb-12, in addition to Mb-6 . This Mb-6 radioimmunoassay system could detect Mb-6 concentrations as low as 100 pg/ml of serum . The coefficients of variation were 4.5% (intra-assay) and 5.1% (inter-assay) . A radioimmunoassay for Mb-12, using anti-midecamycin serum and a {125I}tyramined-Mb-12 derivative, has also been developed . The antiserum was cross-reactive only with Mb-12 among the 9,3"-diacetylmidecamycin metabolites . This Mb-12 radioimmunoassay system could detect Mb-12 concentrations as low as 2 ng/ml . The intra- and inter-assay variances were 5.9 and 5.8%, respectively. Antibiotiki, 1982 Dec, 27(12), 38 - 42 {Changes in the spatial organization of DNA molecules induced by anthracycline antibiotics}; Salianov VI et al.; The optical properties of the mesophases modeling the condensed state of cell DNA molecules formed from the complexes of 7-anthracycline antibiotics with double-stranded low-molecular DNA and polynucleotides were studied . The parameters of the antibiotic binding to the DNA during formation of the mesophases (0.3 M NaCl, 150 mg/ml of polyethylene glycol) are presented . It was found that the CD mesophase spectrum formed from the complex of DNA-antibiotic was characterized by the presence of intensive negative bands in the region of absorption of the chromophores of both DNA and antibiotic . This is indicative of regular spiral organization of the DNA mesophase . Binding of the antibiotic to DNA and polynucleotides was accompanied by changing of the band negative mark (at definite levels of the DNA molecule filling with the antibiotic) in the CD mesophase spectrum to the positive one . It was shown that with respect to the mesophases formed from the complexes of DNA with iremycin and aclacinomycin A no changing in the band marks was observed . Consequently, antibiotics may be conditionally divided into 2 groups . The antibiotics of the first group induce changes in the spin direction of the DNA mesophase, while the antibiotics of the second group had no such effect . It was demonstrated that antibiotic binding with the AT-rich sequences induce more pronounced changes in the mesophase