J Bone Joint Surg Am, 1978 Jan, 60(1), 93 - 6 Concentration of antibiotics in normal bone after intravenous injection; Wiggins CE et al.; The concentrations in serum, cancellous bone, and cortical bone of three antibiotics--nafcillin, cefazolin, and gentamicin--were measured in eleven normal dogs . All antibiotics rapidly penetrated into bone . The peak concentration in serum was reached within twenty minutes of intravenous injections, and the concentration in bone generally paralleled that in serum . Cancellous bone had higher concentrations than did cortical bone because of the admixture of blood. Antibiotiki, 1978 Jan, 23(1), 78 - 87 {Comparative study of the cardiotoxicity of the anthracycline antibiotics, rubomycin, carminomycin and dihydrocarminomycin, in experiments on white mice}; Shepelevtseva NG et al.; The experiments on albino mice treated with rubomycin, carminomycin or dihydrocarminomycin on its 5-fold intravenous administration in doses equal to similar portions of LD50 of the respective antibiotic on its use in a single dose showed that all the 3 antibiotics induced changes in the myocardium close by their character . The heart affections were evident from swelling of separate muscle fibers, degeneration of the myofibrils, homogenization, vacuolization and resorption of the sarcoplasma, pathological changes in the nuclei, atrophy of some muscle fibers . Rubomycin had the highest cardiotoxic effect . Then followed dihydrocarminomycin and carminomycin . All the antibiotics studied in the experiments with mice had mainly an inhibitory effect on the lymphoid hemopoiesis . The effect of carminomycin was the highest . The animal death during the injections and immediately after administrations of the antibiotics must be due to their suppressing effect on hemopoiesis . The deaths at more remoted periods must be due to the cardiotoxic effect of the antibiotics. Antibiotiki, 1978 Jan, 23(1), 26 - 30 {Study of the antibiotic parvulomycin . The isolation of alpha,alpha-trehalose and L-glutamic acid}; Puskas M et al.; A non-reducing disugar and amino acid were isolated in the studies on the structure of parvulomycin . The acid hydrolysis of the disugar revealed the presence of 2 moles of D-glucose . Acetylation of the disugar resulted in formation of octa-O-acetyl-alpha,alpha-tregalose, saponification of which resulted in formation of alpha,alpha-tregalose . Its physical parameters, i.e . melting point of the mixed sample, optical rotation, IR-spectrum coincided with those of the authentic alpha,alpha-tregalose . The isolated amino acid proved to be L-glutamic acid on thin-layer chromatography with witness and comparison of the physico-chemical properties of their hydrochlorides. Am J Med, 1978 Jan, 64(1), 127 - 32 Granulocytopenia in hospitalized patients . II . A prospective comparison of two antibiotic regimens in the empiric therapy of febrile patients; Gurwith M et al.; The results of empiric antibiotic therapy in 126 hospitalized patients with fever during 192 episodes of granulocytopenia were studied . Febrile granulocytopenic patients were randomly allocated to receive either carbenicillin, methicillin and gentamicin, or carbenicillin and cephalothin . The response rate for the two antibiotic regimens was similar, 49 (60 per cent) of 81 responded to the former and 42 (54 per cent) of 78 to the latter . The response rate in patients receiving other antibiotics because of specific indications or counterindications was 19 (58 per cent) of 33 . Thirty-nine (35 per cent) of 110 patients who responded to initial antibiotic therapy had an increase in circulating granulocytes of one log10 or more compared to only 10 (12 per cent) of 79 nonresponders with such an increase . The mortality rate in adult patients receiving carbenicillin, methicillin and gentamicin was eight (16 per cent) of 51, compared to 18 (37 per cent) of 49 in those receiving cephalothin and carbenicillin (P less than 0.05) . The significance of this difference in the initial response rate or mortality rate between patients treated with the two antibiotic regimens when only patients with documented bacterial infection were considered . Patients who responded to their initial antibiotic regimen, and patients for whose fever no explanation was found, had the best prognosis. Phys Ther, 1978 Jan, 58(1), 32 - 4 Antibiotic iontophoresis in the treatment of ear chondritis; LaForest NT et al.; This apparently successful management of suppurative ear chondritis by employing antibiotic iontophoresis does suggest a clinical potential for the use of the procedure . The authors recommend further research to document the efficacy of this procedure as this clinical report does not involve a large sample or sufficient experimental controls, such as selection of medication, dosage values, and confirmation of tissue content of the medication . Factors favoring the trial use of antibiotic iontophoresis, particularly before the permanent disfigurement of extensive chondrectomy or amputation, are 1) reported past experimental confirmation of the effectiveness of iontherapy, 2) the expected small incidence of procedural complications, 3) the ease of application, and 4) the usual absence of discomfort. Arzneimittelforschung, 1978, 28(1), 72 - 5 {Antibiotic concentration in postoperative wound fluid during short-term prevention with cephalosporins}; Wewalka G et al.; Antibiotic concentrations were measured in wound fluid from Redon-drains and in serum during short-time prophylaxis in orthopaedic surgery . 1 . Chephaloridine and cephazolin concentrations in wound fluid rose to therapeutic levels . 3 h after i.v . application of 1 g concentrations in wound fluid and in serum were nearly identical . 6 and 12 h after application the concentrations in wound fluid were significantly higher than those in the serum . 2 . At the end of the 12-h interval of administration the mean concentrations of both antibiotics as well in wound fluid as in serum remained at therapeutic levels . 3 . For reasons of their good diffusion into the wounds both cephaloridine and cefazolin should be appropriate for short-time prophylaxis in orthopaedic surgery. J Hyg Epidemiol Microbiol Immunol, 1978, 22(3), 344 - 53 Observation of antibody activity against antibiotics in patients with atopic disease; Lochmann O et al.; Antibodies to antibiotics were studied in patients hypersensitive to these preparations and in patients with other types of allergic disease . In addition to examining these antibodies, a whole series of other immunological tests were carried out (IgG, IgA, IgM, IgE, C'3 and OPI) . Antibodies to antibiotics were found in a high percentage of subjects, not only in those hypersensitive to antibiotics but also in patients with asthma bronchiale and rhinitis pollinosa . The considerable differences in IgG and IgE observed in patients with high titres of haemagglutinating antibodies to antibiotics point out the blocking character of these antibodies. Folia Microbiol (Praha), 1978, 23(5), 385 - 8 Biosynthesis of fatty acids and sterols in relation to the antibiotic formation in Oudemansiella mucida; Nerud F et al.; The production of mucidin by the basidiomycete Oudemansiella mucida was negatively influenced by the application of D-glucitol as the main carbon source, the effect being independent of the growth rate of the mycelium . The rate of fatty acid synthesis was measured by incorporation of 1-14C-acetate . After 8 days of cultivation, the amount of fatty acids was approximately half that synthetized during cultivation on glucose . The specific rate of incorporation reached its maximum after seven days of cultivation . Incorporation of 2-14C-MEValonate into sterols was the same under the two sets of cultivation conditions . Acetate units from the degraded fatty acids are probably also utilized for antibiotic synthesis. ORL J Otorhinolaryngol Relat Spec, 1978, 40(1), 53 - 63 Potentiation and its mechanism of cochlear damage resulting from furosemide and aminoglycoside antibiotics; Ohtani I et al.; The severe ototoxic interaction of the combined administration of furosemide and aminoglycoside antibiotics (kanamycin, streptomycin and gentamicin) was studied in rabbits, and its mechanism clarified . Severe damage occurred not only in the inner ear but also in the kidney when both furosemide and aminoglycoside antibiotics were administered to rabbits . Kanamycin concentration after a single injection of kanamycin with furosemide was much higher not only in the perilymph but also in the cerebrospinal fluid and serum than that after a single injection of kanamycin alone . The ototoxic interaction following the combined use of furosemide and aminoglycoside antibiotics seems to be caused mainly by the inhibitory effect of furosemide on the excretion of aminoglycoside antibiotics from the kidneys. Infection, 1978, 6(2), 57 - 64 Binding of aminoglycoside antibiotics to human serum proteins . III . Effect of experimental conditions; Rosenkranz H et al.; The binding of several aminoglycoside antibiotics to human serum proteins was studied under varying experimental conditions . The protein binding was determined by means of equilibrium dialysis and, with sisomicin and gentamicin, also by the ultracentrifuge method in the presence and in the absence of Ca++ and Mg++ ions . The technical experimental procedure (dialysis, ultrafiltration, ultracentrifugation) has no effect on protein binding contrary to the physico-chemical conditions (varying concentrations of Ca++ and Mg++ ions) . Under experimental conditions closely conforming to physiological conditions, the aminoglycosides of the kanamycin and neomycin series are not bound by the serum proteins, independent of the assay method used, whereas streptomycin is bound under these conditions . In the absence of divalent cations all the aminoglycosides studied were bound by the serum proteins to varying degrees; the fewer the OH groups contained in the aminoglycoside molecule the greater the rate of protein binding . At equal protein concentration, the albumin fraction of the serum has as great a binding capacity for sisomicin as gamma globulin . Alpha-1 and beta-1 globulin, however, are unable to bind sisomicin. J Membr Biol, 1978, 40 Spec No, 331 - 45 Effect of the polyene antibiotic filipin and the calcium ionophore A23187 on sodium transport in isolated frog skin (Rana temporaria); Nielsen R; Addition of filipin (50 micrometer) to the inside bathing solution of the frog skin resulted in a transient increase in the active sodium transport {measured as short-circuit current (SCC)} . The filipin-induced increase in the SCC required the presence of calcium . The calcium ionophore A23187 (4 micrometer) also induced a transient increase in the SCC . After the activation of the SCC by A23187, the SCC could not be activated by filipin . This indicates that the polyene antibiotic filipin acts as a calcium ionophore . Higher concentrations (40 micrometer) of A23187 resulted in a shrinking of the cells in the transporting cell layer . A23187 also increased the potassium-42 exchange in the isolated epithelium . It is suggested that calcium ionophores enhanced the intracellular calcium concentration; this increase in the calcium concentration resulted in an increase in the potassium permeability of the inward-facing membrane . The increase in the potassium permeability might explain the observed increase in the SCC. Scand J Infect Dis Suppl, 1978, (14), 86 - 91 Bacterial persistence in vivo: resistance or tolerance to antibiotics; Acar JF et al.; The in vivo persistence of bacteria in spite of "adequate" therapy may be due to a variety of causes or factors . The most "obvious" cause is the presence of drug resistant strains, missed in conventional testing because of heterogeneity of resistance, special test requirements or emergence during treatment . A second large group of causes is due to atypical forms, whereas a third cause is due to tolerance . A fourth group of causes may be termed invironmental factors, and this includes drug inactivation, bioconversion or antagonism, often a result of the infection itself. Scand J Infect Dis Suppl, 1978, (14), 225 - 27 A review of experimental models for studying the tissue penetration of antibiotics in man; Raeburn JA; Measurement of tissue antibiotic levels is of great importance in developing rational treatment for infection, particularly in patients whose host defense systems are compromised . This review outlines some of the main approaches to this problem, giving examples of the application of the new techniques in different clinical situations. Scand J Infect Dis Suppl, 1978, (14), 172 - 6 Penetration of antibiotics into bile; Mashimo K; In experimental cholecystitis in dogs, the eradication of E . coli with ampicillin, chloramphenical and kanamycin, all of which showed nearly the same MICs for this bacterial species, varied according to the differences in the penetration of the antibiotics through the liver into the bile . Antibiotics such as cephalothin and rifampicin, which are partially metabolized in the liver to inactive forms, showed higher biliary levels in CCl4-damaged animals than in the normal ones . The results were considered to be due to a reduction in the inactivating effect of esterases in the liver cells . These esterases were mainly found in the cytosol fraction and their intracellular distribution differed from that of esterases for aspirin and/or phenyl acetate. Recent Results Cancer Res, 1978, 63, 230 - 40 Adriamycin and other anthracycline antibiotics under study in the United States; Benjamin RS; Adriamycin is now firmly established as a drug with a very broad spectrum of antitumor activity . It has had a major impact on the therapy of sarcomas . The dose response effect in this tumor is steep and combinations which compromise the dose of adriamycin too greatly are showing inferior results . In lung and breast cancer combinations with adriamycin have been extensively tried . The FAC Regimen in breast cancer has given excellent results at the M.D . Anderson Hospital . The inclusion of adriamycin in combinations has had an impact in the poor prognosis histologies of non-Hodgkin's lymphomas . The CHOP regimen is one of the best developed to date for diffuse histiocytic lymphomas . In the leukemias adriamycin is probably equivalent to daunorubicin which has been more extensively used in this country . A new analog called Rubidazone has shown good activity in AML with a smooth induction and its incorporation into combination with Ara-C, vincristine and prednisone in a regimen called ROAP is being investigated . Adriamycin in complex with DNA has been clinically evaluated, but at this time, no advantage for this approach can be demonstrated. Recent Results Cancer Res, 1978, 63, 1 - 19 Summary of clinical data on antitumor antibiotics in Japan; Koyama Y; In breast cancer, mitomycin C may be a useful drug as an adjuvent to surgery and radiotherapy . The results indicate how difficult it is to obtain statistically significant results and that new ideas are necessary to advance the chemotherapy on solid tumors. J Int Med Res, 1978, 6(5), 414 - 7 A comparison of the minimum inhibitory concentrations of sisomicin and of fourteen other antibiotics; Pitzus E et al.; The activities of sisomicin and of fourteen other antibiotics have been compared for their inhibitory activity on all the different strains of bacteria isolated from a 3,000 bed hospital . The antibiotic sensitivity tests were performed in liquid medium and expressed as minimum inhibitory concentrations . The tests were performed over a period of four months . The results are discussed. J Med, 1978, 9(6), 433 - 43 Effect of antibiotics on platelet thromboplastic function and thrombin activity; Nakahara M; Carbenicillin (CB-PC), sulphobenzylpenicillin (SB-PC), ampicillin (AB-PC), benzylpenicillin (PCG), cefazolin (CEZ), cephalothin (CET) and cephaloridine (CER) were used in vitro for the experiments . Recalcification time was prolonged by AB-PC, SB-PC, CB-PC and CER at the 10(-2) and 10(-3) M level . Prothrombin time (PT) was prolonged by AB-PC, CEZ, CET and CER at the 10(-2) M level . Plasma antithrombin activity was not affected by any antibiotics tested at the 10(-2) and 10(-3) M level . The platelet thromboplastic function of the human platelet suspension and free platelet factor III were reduced more than 40% by all antibiotics used except for PCG at the 10(-3) M level compared with controls, showing no significant difference in the degree of reduction between these two samples . When antibiotics were preincubated with albumin solution, the reduction of platelet thromboplastic function was greatly inhibited except with CB-PC and CER . Factors of bleeding caused by intramuscular injections of the antibiotics are discussed. Scand J Infect Dis Suppl, 1978, (14), 313 - 5 Tissue penetration of antibiotics; an overview; Sabath LD; The recent development of several techniques has made it possible to more adequately study the tissue penetration of various antibiotics . The major technical advances making this possible have been various assay systems permitting measurement of antibiotics in very small amounts of fluid or tissue . In addition, various tissue cages and the use of skin blisters has been a popular means for testing antibiotic penetration into extra-cellular fluid. Scand J Infect Dis Suppl, 1978, (14), 267 - 72 Pharmacokinetic study of beta-lactam antibiotics in bronchial secretions; Bergogne-Berezin E et al.; The objective of the study was to evaluate the concentrations obtained in serum and bronchial secretions after administration of five beta-lactam antibiotics: cephradin (1 g per os) and cefoxitin (2 g i.v . infusion), amoxycillin (1.0 g per os), bacampicillin (0.4 g and 0.8 g per os) and ampicillin (1.0 g per os) . 123 adult patients were included in the study and received a single dose of the tested drug . Serum and mucus samples were collected simultaneously 30 minutes, 1, 2 or 4 hours after administration of the drugs . Mucus samples were taken by fibroscopy but in some patients the samples were collected through a tracheostomy cannula which allowed sampling at different time intervals . The results show that the concentrations of penicillins in bronchial secretions increase progressively between one and four hours after administration of the drugs . Bronchial levels obtained after oral administration of ampicillin are low, not more than 5 to 10% of serum levels . The other antibiotics tested show worthwhile concentrations in bronchial secretions, especially with cephalosporins and bacampicillin which exhibits higher serum and bronchial concentrations than ampicillin. Scand J Infect Dis Suppl, 1978, (14), 262 - 6 Clinical significance of tissue penetration of antibiotics in the respiratory tract; Lambert HP; Concentrations of antibiotics in bronchial secretion vary widely and cannot be easily related to physico-chemical characteristics . Serum and sputum concentrations do broadly correlate in the case of penicillins, some cephalosporins and some tetracyclines . Antibiotic concentrations in bronchial secretion (although not necessarily in lung tissue) are always much lower than in serum, with a ratio of about 20% for tetracycline, 3--4% for ampicillin, 4--50% for gentamicin and tobramycin . Concentrations will often be adequate to inhibit highly sensitive pathogens but marginal or ineffective for those less sensitive, e.g . carbenicillin or gentamicin for Ps . aeruginosa. Scand J Infect Dis Suppl, 1978, (14), 214 - 20 Comparison of antibiotic assays using different experimental models and their possible clinical significance; Holm SE et al.; Different experimental models were applied to study the pharmacokinetics of antibiotics in "interstitial fluid" ("i.f.") in rabbits . Two types of tissue cages were used and the results from these experiments were compared with those obtained analysing the antibiotic concentration in the mucous membrane of the oral bucca and maxillary sinus in rabbits . A similar determination was done in the mucous membrane of sinus in man . The concentration of antibiotics in the "i.f." from steel-net chambers in rabbits closely follows that of the mucous membranes of the maxillary sinus in man and the oral bucca in rabbits . Experimental bacterial infections of the tissue cages resulted in decreased amounts of biologically active antibiotics in the "i.f." for some antibiotics compared to that of the uninfected cages . An increase of the concentration of antibiotics in the infected cages was noted simultaneously with a decrease in the number of viable bacteria during the healing process . The clinical significance of the models will be discussed. Scand J Infect Dis Suppl, 1978, (14), 127 - 34 Tissue cage experiments with beta-lactam antibiotics in rabbits; Carbon C et al.; An animal model in which antibiotic concentrations can be meausred in intersittial fluid (IF) withdrawn from subcutaneous tissue cages has been used . Although the physiological significance of IF is not well established, this model allowed the comparison of 1) two pharmacological forms of the same drug (bacampicillin and ampicillin were compared after a single oral dose; and 2) drugs of the same group in a single i.m . injection study and in a cumulative effect study . These data provide new criteria for clinical choice of antibiotics . A rapid penetration into IF can be explained by a low degree of serum protein binding, but a highly bound drug is not restricted to the intravascular space . In this animal model we have also shown that an 0.25 h i.v . infusion of cephalothin induced higher IF levels than an i.v . bolus injection and an 1 h i.v . infusion . Using a single i.v . bolus injection of various cephalosporins, we have shown that a two open compartment model cannot explain both serum and IF data . Sustained late IF levels suggested the hypothesis of a deep compartment. Scand J Infect Dis Suppl, 1978, (13), 58 - 62 Implanted tissue-cages: a critical evaluation of their relevance in measuring tissue concentrations of antibiotics; Ryan DM; In several species of laboratory animals, the concurrent serum and tissue-cage fluid levels of several antibiotics after a single parenteral dose have markedly different profiles . New work has shown that these differences are mainly due to the relatively impermeable granulomatous sheath which develops around the implanted tissue chambers . The concentrations of an antibiotic in tissue-cage fluid are therefore not representative of its concentration in "interstitial fluid" or extravascular fluid in general . Tissue-cage levels are probably more representative of antibiotic levels to be found inside abscesses, in chronic disease situations, or relatively avascular sites in the body. Scand J Infect Dis Suppl, 1978, (13), 47 - 51 Experimental models for studies on transportation of antibiotics to extravasal compartments; Holm SE; A short review is presented illustrating different methods employed to determine the antibiotic concentration in different tissues in man and the limitation to perform thorough pharmacokinetic studies . The most often used experimental models (different tissue cage models the fibrin clot, skin blisters, skin windows, skin chambers) applied in animal and man for studies of antibiotics are presented as well as a discussion concerning their relevance to the clinical situation. Cancer Chemother Pharmacol, 1978, 1(2), 83 - 90 The role of antitumor antibiotics in current oncologic practice; Davis HL Jr et al.; The antitumor antibiotics have thus made a major impact on oncologic practice . The continued search for productive strains of these organisms should be encouraged; in addition, the activity and toxicity spectrum suggests the need for vigorous analogue development . An active anthracycline devoid of cardiotoxicity, a bleomycin with no effect on pulmonary tissue, an analogue of streptozoticin devoid of nephrotoxicity -- these would be advances of inestimable benefit to the cancer patient of the future. Recent Results Cancer Res, 1978, 63, 21 - 9 Role of antitumor antibiotics in current oncologic practice; Davis HL Jr et al.; The antitumor antibiotics have thus made a major impact on oncologic practice . The continued search for productive strains of these organisms should be encouraged . In addition, the activity and toxicity spectrum suggests the need for vigorous analog development . An active anthracycline devoid of cardiotoxicity; a bleomycin with no effect on pulmonary tissue; an analog of streptozotocin devoid of nephrotoxicity; these would be advances of inestimable benefit to the cancer patient of the future. Antibiotiki, 1978 Jan, 23(1), 58 - 62 {Experimental study of the antiviral properties of antibiotic 6734-21}; Goncharskaia TIa; The effect of antibiotic 6734-21 on the viruses of variolovaccine, Herpes simplex, influenza and classical avian plague was studied on various experimental models . Antibiotic 6734-21 inhibited development of the variolovaccine virus in the tissue culture, in chick embryos, in rabbits with variolovaccine infection, as well as the development of the viruses of Herpes simplex, Aueski, and Newcastle diseases in the tissue culture . It had a virulicidic effect on the viruses of variolovaccine, influenza and classical avian plague. C R Seances Soc Biol Fil, 1978, 172(4), 748 - 51 {Dwarf colony mutants of Escherichia coli: plasmids resistant to antibiotics}; Borderon E et al.; Deficient dwarf colony (DDC) mutants of E . coli K 12, harboring or no resistance plasmids, were obtained in vitro . The R plasmids of parental strains and to DDC mutants were transfered by conjugation to normal colony, and to DDC mutants of E . coli K 12; the frequencies of transfer were similar for all strains studied. C R Seances Soc Biol Fil, 1978, 172(4), 609 - 27 {Mechanism of action of antibiotics:some examples}; Michel-Briand Y; Antibiotics are very commonly used substances to eradicate bacterial infections by bacteriostatic or even bactericid effect . They act at a very specific stage (target), although other less important or secondary interactions can occur . We studied the interaction of three antibiotic families (beta-lactamins, aminosides, rifampicin) with bacterial cell . Penicillin disturbs the cell wall synthesis and more accurately the glycopeptide (or murein) formation, a substance giving rigidity or shape to bacteria . It acts in the late phase of murein-biosynthesis, when N-acetyl glucosamin -- N-acetyl muramic acid L ala -D glu M-DAP (L lys) -D ala -D ala are linked together by the peptide part, under the effect of several enzymes, particularly transpeptidase and DD-carboxy-peptidase . It would appear that beta-lactame-thiazolidine rings have a steric analogy with dipeptide D-alanyl D-alanine . The result would be that the enzyme would act on the antibiotic instead of peptide: the consequence would be inhibition of the peptidic link, giving an abnormal murein, and an incomplete cell wall i.e . fragile bacteria . Aminosides, particularly Streptomycin, link themselves to 30 S subunit of bacterial ribosome . In this case, it seems that it is a 3''OH function which reacts with lysine (from S 12 protein part of 30 S subunit) . The consequence is an alteration in the RNA messager lecture, and a false traduction and consequently protein biosynthesis stops with a decrease of polyribosomes and of the formation of inert 70 S ribosome . Rifamycins, and particularly Rifampicin act by inhibition of RNA messager synthesis . One molecule of antibiotic links itself to one molecule of RNA messager : hydroxyl and cetone function in C1 Cs C21 C23 and "ansa" bridge link to beta subunit of RNA polymerase . This linkage gives a conformational change to the RNA polymerase-DNA complex, inhibiting the catalytic action of this enzyme, and consequently stopping RNA messager and protein synthesis . The study of the action mechanism of these antibiotics enables us to show the action specificity of these products in the bacteria . This specificity is more accurate when the target is not to be found in the eucaryotic cells : in this case the antibiotic may be considered as entirely atoxic . If the study of the action mechanism of antibiotics gives a better understanding of the use of these drugs, their action at a definite stage in bacterial metabolism is a valuable tool for scientists in their approach to cell functioning. Acta Microbiol Acad Sci Hung, 1978, 25(4), 299 - 306 Defective life cycle and low antibiotic production in submerged cultures of Streptomyces fradiae; Vargha G et al.; The life cycle of a Streptomyces fradiae strain producing high amounts of neomycin under industrial conditions has been investigated in liquid soybean medium where the production of antibiotic proved to be comparatively low . The changes occurring in the main macromolecular components and the enzyme activities of the mycelium during the life cycle and cytological observations proved that there was a block in the normal proecess of reproductive differentiation and a lack of exocellular alkaline phosphatase activity was found. Zentralbl Bakteriol {Orig A}, 1978, 242(3), 387 - 93 A simple micro agar diffusion method for the determination of antibiotic concentrations in blood and other body fluids; Georgopoulos A; A micro agar diffusion method to determine antibiotic levels in only 0.02 ml of serum is described . With this technique, standard curves for Ampicillin, Penicillin G, Gentamicin, Tetracycline HCl and Amphotericin B were calculated . The method displays a good reproducibility with an error of less than 10% . To compare this technique with a conventional macro agar diffusion method fixed antibiotic concentrations in rabbit serum were examined . Corresponding results were obtained indicating the equivalence of this method, which thus proved to be suitable to determine antibiotic levels in small volumes of body fluids. Ann Biol Clin (Paris), 1978, 36(4), 363 - 7 {Comparison of two methods of antibiotic sensitivity tests: gel diffusion and automatic method using ABAC apparatus . I . Variation and dispersion of the two methods (author's transl)}; Drugeon H et al.; The authors studied comparatively the sensitivity of 3 bacterial strains (P . Aeruginosa and two E . coli) with regard to antibiotics using an automatic method (ABAC) compared with a gel diffusion technic with impregnated disks . Each strain was tested by both methods 50 to 55 times . The diffusion method was easily reproducible with an average standard deviation of 2.23 mm . Its results were in agreement compared with the average diameter of measurements in 93.3% of cases . The automatic method gave results which agreed together in 95.7% of cases . It is thus reproducible . If one compares it with the results of the diffusion method, considered here as the reference method, we obtained the same response in 86.3% of cases . In 13.7% there was disagreement in interpretation (in most cases, the strain found intermediate in gel diffusion was considered sensitive on autoanalysis). Scand J Infect Dis Suppl, 1978, (14), 151 - 9 Factors affecting the intraocular penetration of antibiotics . The influence of route, inflammation, animal species and tissue pigmentation; Barza M; Antibiotics which are sparingly lipid-soluble, such as the penicillins, cephalosporins and aminoglycosides, penetrate the eye with great difficulty, achieving intravitreal concentrations which are only a small percentage of the peak serum level . As a result, it is common practice to administer these agents by periocular injection . We have compared the penetration of gentamicin in albino rabbits with that in squirrel monkeys, in normal and infected eyes, after retrobulbar and subconjunctival administration . Generally speaking, the subconjunctival route produced levels equal to or higher than those resulting from retrobulbar injection in both species; it was distinctly superior with regard to cornea and aqueous humor . Inflammation had a neutral or enhancing influence upon intraocular penetration in the monkey, but had a more variable effect in the rabbit; this may be related to the balance between diminution of the blood-ocular barrier and increased dissipation of antibiotic into the systemic circulation . Interspecies differences were much more striking in normal than in infected eyes . This underlines the necessity for the investigator to study inflamed eyes if the results are to be relevant to the clinical situation . Iris and choroid-retina from pigmented rabbits contained significantly more clindamycin and less gentamycin and less gentamicin, in terms of diffusible drug, than tissues from albino animals . These discrepancies reflect opposite interactions between melanin and the two antibiotics in vivo. Recent Results Cancer Res, 1978, 63, 288 - 97 Clinical evaluation of new antitumor antibiotics; Muggia FM; The clinical evaluation of new antibiotics and their analogs requires detailed analysis with respect to the best therapeutic strategy . In the case of anthracycline, diminished cardiac toxicity is as important an aim as increased activity . In the evaluation of cardiac toxicity the most important parameter must be the time to toxicity rather than the total dose . The new endomyocardial biopsy technique may be helpful in the study of analogs such as rubidazone, carminomycin and AD32 . Actinomycin D analogs are also of interest, since this drug is part of several curative regimens, but its use has been limited by its severe acute toxicity . In the case of bleomycin, analogs with diminished pulmonary toxicity should be sought. Med Microbiol Immunol (Berl), 1977 Dec 27, 163(4), 269 - 76 Sensitivity of strains of enteropathogenic Escherichia coli to tobramycin and other antibiotics; Konforti N et al.; The sensitivity patterns of strains of enteropathogenic Escherichia coli associated with diarrhoeal disease of infants to tobramycin and other antibiotics were estimated . The activity of tobramycin and of gentamicin alone and in combinations against recent isolates of enteropathogenic Escherichia coli was investigated . It was found that all the strains included in the present study were sensitive to tobramycin and gentamicin and most of them were sensitive to colistin and furazolidone . No significant differences in minimal inhibitory concentrations (MICs) and rates of killing were found between tobramycin and gentamicin, and they acted in an additive manner against most of the strains tested. Nouv Presse Med, 1977 Dec 24, 6(44), 4123 - 4 {Bisalbuminaemia . Three aetiologies: hereditary mutation, antibiotic therapy, pseudocyst of the pancreas (author's transl)}; Andre P et al.; The demonstration of a double albumin line on blood protein electrophoresis has important practical applications: after eliminating congenital bisalbuminaemia, with no pathological consequences, this abnormality may make it possible to detect an overdose of beta-lactamines, requiring the interruption of treatment, or a serious effusion of pancreatic origin justifying surgery. Radiat Environ Biophys, 1977 Dec 12, 14(4), 323 - 8 Effects of antibiotics on UV-stimulated tube growth of Pinus silvestris pollen; Zelles L; Studies were made to investigate the effects of different antibiotics on unirradiated pollen and on pollen with enhanced tube growth, stimulated by low doses of UV-light . The antibiotics mitomycin, chloramphenicol, tetracyclin, penicillin, nystatin and carbony-cyanid phenylhydrazon were not able to suppress tube growth stimulation of pine pollen . The data obtained are discussed in view of the stimulation mechanism of low doses of UVP-light. J Pharm Sci, 1977 Dec, 66(12), 1675 - 9 Physicochemical properties of beta-lactam antibiotics: oil-water distribution; Tsuji A et al.; Apparent partition coefficients Papp, of beta-lactam antibiotics were determined in octanol-water and 2-methylpropanol-water systems at various pH values . The pKa values also were determined by potentiometry under the conditions of partition experiments . The intrinsic partition coefficients for the unionized form, Pu, and the ionized form, Pi, of beta-lactam antibiotics were calculated from the equation Papp = Pu{aH+/(Ka + aH+)} + Pi{Ka/(Ka + aH+)} . The correlation between Pu and Pi values and lipophilic parameters of penicillins measured in other systems was examined. J Infect Dis, 1977 Dec, 136(6), 778 - 83 Standardization of a preparative ultracentrifuge method for quantitative determination or protein binding of seven antibiotics; Peterson LR et al.; A preparative ultracentrifuge method was standardized for determination of quantitative binding of cephalothin, cefamandole, cefazolin, cefaclor, erythromycin, gentamicin, and chloramphenicol to human serum proteins . At achievable in vivo concentrations, serum binding was 78.5% for cephalothin, 79.9% for cefamandole, 88.5% for cefazolin, 23.5% for cefaclor, 41.9% for erythromycin, 22.7% for gentamicin, and 59.5% for chloramphenicol . Techniques that use semipermeable cellophane or diaflow membranes, cross-linked dextran, inhibition of bacterial growth, protein precipitation, or liquid partitioning all have inherent problems with either the ligand or the antibiotic adversely interacting with the experimental apparatus . Ultracentrifugation provides a rapid, reproducible technique for protein-binding determinations of the classes of antibiotics described. Bangladesh Med Res Counc Bull, 1977 Dec, 3(2), 101 - 7 A study on the evaluation of local shati starch as a substitute of polysaccharides used in the preparation of capsules and tablets of antibiotics; Rahman S et al.; Local shati starch was extracted, purified and used as an excipient for the preparation of capsules and tablets of oxytetracycline and chloramphenicol . The weight variation test, disintegration time and hardness test of these dosage forms were done and compared with the conventional maize starch containing tables and capsules of the antibiotics . The results in respect of their potency test were found to conform to official pharmacopoeias (B.P . and U.S.P) . Stability study for over one year of both varieties of tablets and capsules revealed that they retained their potencies equally well. J Antibiot (Tokyo), 1977 Dec, 30(12), 1119 - 22 Blood level studies in chickens, turkey poults and swine with tiamulin, a new antibiotic; Laber G et al.; Tiamulin concentrations have been determined in the serum of chickens, turkeys and swine after a single oral administration of various doses . The compound peaked between 2 and 4 hours after drug supply . In the highest dose used (50 mg/kg body weight), mean concentrations of 3.5, 2.9, 4.5 microgram/ml for chickens, turkeys and swine, respectively, could be obtained . In poultry, the levels declined between 12 and 24 hours to values not useful for calculation . In swine at 24 hours after administration measurable values could still be detected. J Antibiot (Tokyo), 1977 Dec, 30(12), 1055 - 9 Pholipomycin, a new member of phosphoglycolipid antibiotics . II . Physico-chemical properties and comparison with other members of this family of antibiotics; Arai M et al.; Physico-chemical characterization of pholipomycin revealed that this antibiotic is a new member of phosphoglycolipid antibiotics . Pholipomycin was differentiated from other members by the products formed on acid hydrolysis as follows: the presence of glucosamine, a 257 nm chromophore and moenocinol-type C25 lipids, but the absence of glucose, 6-deoxyglucosamine and glycine. Antibiotiki, 1977 Dec, 22(12), 1113 - 6 {Penetration of polyene antibiotics into human embryonic kidney tissue cell cultures}; Kravchenko LS et al.; Penetration of 14C-amphotericin AM-2 into the cells of the tissue culture of the human embryon kidneys was studied by means of light autoradiography after incubation with the antibiotic . Microscopic examination of the autographs of the cell slices revealed the presence of the radioactive label in the cytoplasm and nucleoplasm of the cells . The revealed intracellular localization of the label was evident of the antibiotic penetration into the cells. Antibiotiki, 1977 Dec, 22(12), 1117 - 21 {Antibiotic sensitivity and pyocin dependence of clinical strains of Ps . aeruginosa}; Savitskaia KI et al.; The effect of antibiotics on clinical strains of Ps . aeruginosa was analyzed . It shown that 92 per cent of the strains had multiple resistance to the most of the antibiotics used in the clinic . All the strains were sensitive to gentamicin and polymyxin . The apyocinogenic strains of Ps . aeruginosa were more sensitive to the effect of the antibiotics than the pyocinogenic ones. Proc Natl Acad Sci U S A, 1977 Dec, 74(12), 5239 - 43 Transition state structures of a dipeptide related to the mode of action of beta-lactam antibiotics; Boyd DB; The tetrahedral adducts formed during nucleophilic attack by a hydroxyl ion on the carbonyl carbon of a model dipeptide, glycylglycine, were studied by modified-intermediate-neglect-of-differential-overlap molecular orbital calculations . This dipeptide is taken to represent the D-alanyl-D-alanine terminus of the polypeptides involved in the cross-linking transpeptidation reaction of peptidoglycan in bacterial cell walls . It was found that nucleophilic attack on one face of the carbonyl carbon leads to a transition intermediate species structurally similar to that afforded by the bicyclic nucleus of penicillins and cephalosporin antibiotics . The results support the concept that the beta-lactam antibiotics, which are known to inhibit various bacterial cell wall enzymes, may act as transition state analogs . Also, the structure formed from nucleophilic attack on the so-called alpha face of the dipeptide is more similar to the antibiotic structures than is that from attack on the opposite face . In agreement with other types of experiments, the results suggest that the alpha face may be the one approached by a nucleophile in the receptor site(s) of the appropriate cell wall enzymes. Proc Natl Acad Sci U S A, 1977 Dec, 74(12), 5207 - 11 Netropsin-poly(dA-dT) complex in solution: structure and dynamics of antibiotic-free base pair regions and those centered on bound netropsin; Patel DJ et al.; The biphasic duplex-to-strand transition for the netropsin.poly(dA-dT) complex, phosphate/drug mole ratio (P/D) = 50, has been investigated by high-resolution proton nuclear magnetic resonance (NMR) spectroscopy at the nonexchangeable base and sugar protons in 0.1 M cacodylate solution . The NMR spectral parameters monitor the structure and dynamics of the opening of antibiotic-free base pair regions (55 degrees-65 degrees) and the opening of base regions centered on bound netropsin (90 degrees-100 degrees) . The gradual addition of netropsin to poly(dA-dT) results in structural perturbations extending into the antibiotic-free base pair regions that begin to level off above 0.02 antibiotic molecules per polynucleotide phosphate (P/D = 50) . The NMR chemical shift parameters at the antibiotic-free base pair regions in the P/D = 50 complex suggest changes in the glycosidic torsion angles of the deoxyadenosine and thymidine residues and less pronounced changes in the base pair overlap geometries . The dissociation rates of the antibiotic-free base pair regions are at least an order of magnitude slower in the P/D = 50 netropsin.poly(dA-dT) complex compared to related parameters for poly(dA-dT) and the P/D = 50 ethidium bromide-poly(dA-dT) complex . There is decreased segmental mobility at the antibiotic-free strand regions in the temperature range (65 degrees-90 degrees) between the two transitions in the biphasic melting curve of the P/D = 50 netropsin-poly(dA-dT) complex . Netropsin stabilizes at least five base pairs, with their center at its binding site. Lancet, 1977 Nov 26, 2(8048), 1118 - 22 Changes in hospital antibiotic therapy after a quality-of-use study; Achong MR et al.; During the first quarters of 1976 and 1977, the use of parenteral gentamicin, cloxacillin, ampicillin, and cephalothin was surveyed in 219 (in 1976) and 240 (in 1977) patients admitted to a surgical, a gynaecological, and a medical ward of a teaching hospital . In 1976, therapy was assessed as irrational in 42%, 50%, and 12% of the surgical, gynaecological, and medical patients, respectively; the corresponding figures for 1977 were 24%, 25%, and 22% . The more rational therapy in 1977 was due to a shorter duration of prophylactic therapy; and to fewer patients receiving oral antibiotics just before or after the parenteral antibiotic. Lancet, 1977 Nov 19, 2(8047), 1043 - 5 Prevention of wound infection in abdominal operations by peroperative antibiotics or povidone-iodine . A controlled trial; Galland RB et al.; The wound-infection rate after abdominal operations was compared in 113 patients randomly allocated to an untreated control group, a group receiving preoperative lincomycin and tobramycin, or a group receiving local instillation of povidone-iodine . The wound-infection rate was 8.1% in 37 patients receiving antibiotics, 42.1% in 38 untreated controls, and 39.5% in 38 patients in the povidone-iodine group. Eur J Biochem, 1977 Nov 15, 81(1), 33 - 44 The peptidoglycan crosslinking enzyme system in Streptomyces strains R61, K15 and rimosus . Kinetic coefficients involved in the interactions of the membrane-bound transpeptidase with peptide substrates and beta-lactam antibiotics; Dusart J et al.; The transpeptidation reaction performed by the membranes of Streptomyces strain R61 fits the general rate equation for an enzyme-catalysed bimolecular reaction . The same membranes (E) interact with beta-lactams (I) to form inactive penicillin-enzyme-membrane complexes (EI) of rather high stability, which subsequently break down (E + I leads to EI leads to E + degradation products) . The enzyme is regenerated and the antibiotic is released in the form of an inactive metabolite . With benzylpenicillin, the degradation product is benzylpenicilloic acid . The reaction is heat-labile . The first step of the reaction (E + I leads to EI) is characterized by a second-order rate constant (kformation in M-1 s-1) and the second step (EI leads to E + degradation products) by a first-order rate constant (kbreakdown in s-1) . The effects in vitro of various beta-lactams on the membrane-bound transpeptidase, as expressed by the relevant kformation and kbreakdown values, parallel the effects in vivo of the same antibiotics as expressed by their ability to prevent the germination and growth of conidiospores . The kinetic parameters of the transpeptidase that was solubilized with N-cetyl-N,N,N-trimethylammonium bromide with respect to its interaction with both peptide substrates and beta-lactam antibiotics are quantitatively different from those of the membrane-bound enzyme . Moreover, the solubilized enzyme fragments benzylpenicillin with formation of phenylacetylglycine, a reaction which is similar to that catalysed by the exocellular R61 enzyme . The membranes of Streptomyces strains rimosus and K15 possess an active 'classic' penicillinase . They were not studied but the kinetic coefficients of the corresponding solubilized transpeptidases were determined and compared with those of the solubilized enzyme from strain R61. Antibiotiki, 1977 Nov, 22(11), 981 - 4 {Effect of mutagenic factors on the variability of cultures of Actinomyces griseus--preducer of the antibiotic grisin}; Iustratova LS et al.; The study of the lethal and mutagenic effect of ethylenimine, nitrozoguanidine, nitrozomethylurea and nitrozoethylurea on Act . griseus Krainsky 15, producing grisin, an antibiotic widely used in agriculture as a stimulator of domestic animal growth showed that induction of mutants with increased antibiotic production levels was most favourable under the effect of ethylenimine . The above mutagens were highly active with respect to induction of morphological mutants . No clear correlation between the colony morphology and antibiotic production property was observed . However, it was noted that the dwarf colonies had a significantly decreased antibiotic activity. Antibiotiki, 1977 Nov, 22(11), 977 - 81 {Formation of peroxide compounds and their role in the inactivation of polyene antibiotics levorin and mycoheptin}; Kasaikina OT et al.; The kinetics of peroxide formation in the process of levorin and mycoheptin oxidation at a temperature of 57 degrees C was studied . It was shown that the peroxide compounds actively participated in the processes of levorin and mycoheptin inactivation as intermediate products of their transformation . Addition of the peroxides increased the rate of the antibiotic degradation even if there was no oxygen and subsequently decreased the periods of their storage . Conditions for the use of the iodometric method for determination of the peroxides in the poyenic compounds are discussed. Antibiotiki, 1977 Nov, 22(11), 967 - 70 {Physico-chemical characteristics of the new antitumor antibiotic virenomycin}; Brazhnikova MG et al.; Virenomycin, a new crystalline antitumor antibiotic was isolated from the mycelium of Streptomyces virens . The antibiotic contained: C 64.87 per cent, H 5.66 per cent, methoxylic groups 9.5 per cent . The melting temperature was 255-260 degrees (dec.), {alpha}20D=-17 (c 0.142, chloroform) . Virenomycin had a complex UV spectrum with lambdamax . 245 (677), 265 (453), 275 (542), 287 (507), 395 (222) nm . A chromofor fragment and carbohydrate (C7H14O5) were found in the methanolysis products . Virenomycin was close to antibiotic c B-21085 BY THe physico-chemical properties and differed from it in the character of the UV spectrum and the values of the specific absorption, as well as by the optic rotation in dimethyl sulphoxide and acetic acid. Antibiotiki, 1977 Nov, 22(11), 963 - 7 {Formation of new antibiotic, virenomycin, by a culture of Streptomyces virens sp . nev.}; Gauze GF et al.; A culture of a new species Streptomyces virens was isolated from a soil sample . It produced an antibiotic designated as virenomycin . The antibiotic was mainly synthesized in the mycelium . Only insignificant amounts of it were found in the culture fluid . The optimal nutrient medium for production of virenomycin contained glycerol, soybean meal, ammonium sulphate, sodium chloride and calcium carbonate . Crystalline virenomycin had a comparatively low antitumor activity and narrow spectrum. Antibiotiki, 1977 Nov, 22(11), 1022 - 8 {Combined antibiotic therapy following heart surgery}; Vasina TA et al.; In vitro efficacy of combinations of broad and narrow spectrum semi-synthetic penicillins, broad spectrum semi-synthetic penicillins with macrolides or aminoglycosides and tetracyclines with other biosynthetic antibiotics was studied with respect to the causative agents of surgical infections . Correlation between the sensitivity of the isolates and the antibiotics levels in the organism of the surgical patients was shown . The role of the etiological factor in the development of the post-operative complications in the patients after surgical operations on the heart was elucidated . The most rational schemes of the antibiotic use in therapy of the patients with purulent complications after operations on the open heart were developed and the maximum doses of different semi-synthetic penicillins for the treatment of patients with purulent processes after operations under conditions of artificial blood circulation were determined. J Antibiot (Tokyo), 1977 Nov, 30(11), 987 - 92 Studies on mycobacillin derivatives . IV . O-methylation of the antibiotic and identification of the active tyrosine residue; Banerjee PC; Methylation of myocobacillin with dimethyl sulfate and methyl iodide produced respectively mono- and di-methyl derivatives . the products were inactive against fungal spores and erythrocytes . Tyrosine hydroxyl groups only were methylated; in the monomethyl derivative, the hydroxyl of the tyrosine residue in position 6 is methylated, whereas the hydroxyl of the tyrosine in position 4 remains free; both hydroxyl groups are methylated in the dimethyl derivative . The results indicate that the hydroxyl group of the tyrosine residue in position 6 is essential for the biological activity of mycobacillin. J Antibiot (Tokyo), 1977 Nov, 30(11), 965 - 8 Synthesis of a 125I-labelled derivative of the antibiotic griseofulvin; Lecointe P et al.; A derivative of griseofulvin has been synthesised, in which the 2'-O-methyl group is replaced by a 2'-(2-iodoethoxy), 125I-labelled group . This derivative is at least as potent as griseofulvin itself, when assayed for inhibition of growth on the Myxomycete Physarum polycephalum. Mikrobiologiia, 1977 Nov-Dec, 46(6), 1095 - 1102 {Lysis from without of a culture of Actinomyces griseus--producer of the antibiotic kormogrizein}; Rautenshtein IaI et al.; A polylysogenic culture of Actinomyces griseus 15 producing the antibiotic cormogrisin is sensitive to actinophages, denoted as types 15 I, 15 II and 15 III, which are the virulent mutants of its temperate phages . In certain cases, the variants of Act . griseus 15, obtained by selection and resistant to the phages types 15 I and 15 II, can undergo lysis-from-without by these phages . A study of the mechanisms involved in this phenomenon has shown that the lytic activity is entirely eliminated if the phages have been a titre of 10(9) and higher . The lytic activity is entirely eliminated if the phages have been treated with a specific serum or inactivated by UV . The variants resistant to phage 15 I can adsorb this phage and undergo lysis-from-without at a high multiplicity of infection if only the age of the variant does not exceed 13 hours . The variants resistant to phages 15 I and 15 II can undergo lysis-from-within under the action of phage 15 III . The variants resistant to this phage have acquired this resistance as a result of lysogenization . They have entirely retained the ability to adsorb phage 15 I, but their ability to absorb phage 15 III is much lower . Therefore, the rate of mycelium growth is only slightly inhibited, but the lysis of the culture is not observed, under the action of phage 15 III having titres of 10(9) and 10(10). Med J Aust, 1977 Oct 8, 2(3 Pt 2 Suppl), 19 - 22 Principles of concomitant antibiotic therapy; Weinstein AJ; There are five major disadvantages of the combined use of antibiotics: (i) antibiotic antagonism; (ii) a "false sense of security"; (iii) increased toxicity; (iv) suprainfection; and (v) increased cost . Four situations clearly require the use of antibiotic combinations: (i) to produce antibiotic synergism; (ii) to prevent the emergence of resistant organisms; (iii) to treat mixed infections, such as brain abscess, peritonitis, and pelvic infections; and (iv) to institute therapy for severe infections. J Dairy Sci, 1977 Oct, 60(10), 1655 - 61 Persistence of antibiotics in milk from cows treated late in the dry period; Johnson ME et al.; Nineteen cows were treated via intramammary infusion at various times prior to calving with one of two dry cow antibiotic preparations (cloxacillin or penicillin) . Milk samples from these cows after calving were analyzed for antibiotic residues by the Sarcina lutea cylinder plate method . Eight cows were treated with cloxacillin was detected in the milk of only two cows after calving and then for only one milking, so no problem should exist with cloxacillin if the manufacturer's recommendations are followed . Penicillin residues were not detected in milk samples taken from cows treated more than 9 days prior to calving with the dry cow penicillin preparation . However, seven of nine cows treated with penicillin up to 9 days prior to calving had detectable penicillin residues in the milk from treated quarters after calving . Only one cow had detectable penicillin residues longer than the manufacturer's recommended milk withholding time of 96 h, and this cow was treated only 3 days prior to parturition . Normal routine on a dairy farm and adherence to manufacturer's recommendations should result in no antibiotic residue problems in milk from cows treated during the dry period for mastitis control with either cloxacillin or penicillin. Acta Pathol Microbiol Scand {B}, 1977 Oct, 85B(5), 347 - 9 Treatment of Mycoplasma hyorrhinis contaminated tissue cultures with a mixture of antibiotics; Ulrich K et al.; Results obtained using a combination of antibiotics to control mycoplasmas in tissue cultures are described . Cell strains and established cell lines from several mammalian species grown in tissue culture were found to be highly contaminated with M . hyorrhinis . Cultures were treated with a mixture of three antibiotics consisting of gentamicin, tetracycline and chloramphenicol, and since that time tests for mycoplasmas in the treated cultures have consistenly yielded negative results . Apart from a transient cytostatic effect on the cells during the treatment, no apparent unwanted effects were observed . The mixture of three antibiotics appeared to be superior to treatment with antibiotics singly or combinations of two antibiotics. J Antibiot (Tokyo), 1977 Oct, 30(10), 856 - 60 Ring formation in a pentapeptide with alternating L and D residues: an analogy to cyclization in the biosynthesis of peptide antibiotics; Bodanszky M et al.; Acetylation of L-isoleucyl-D-alanyl-D-alanyl-L-valyl-D-leucine with acetic anhydride followed by methylation with diazomethane yielded the expected acetylpentapeptide methyl ester with molecular weight 541, but also resulted in the formation of a by-product with molecular weight 555 . The incorporation of the mass corresponding to CH2 seems to be due to ring closure--via a mixed anhydride--and methylation of the cyclol derivative thus formed . A preferred, ring-like conformation stabilized by intramolecular hydrogen bonds that in turn are the consequences of the alternation of D- and L- residues in the sequence, is invoked as explanation for the unexpected cyclization . This assumption is supported by the conversion of the pentapeptide methyl ester to desthiomalformain in molten imidazole. J Antibiot (Tokyo), 1977 Oct, 30(10), 789 - 805 Tallysomycin, a new antitumor antibiotic complex related to bleomycin . II . Structure determination of tallysomycins A and B; Konishi M et al.; The structures of tallysomycins A and B, two major components of a new antitumor antibiotic complex, have been determined . They are glycopeptide antibiotics structurally related to bleomycin: four amino acid moieties and a disaccharide fragment which are the constituents of bleomycin molecule are also present in the tallysomycins . Tallysomycins A and B contain two new amino acids and a unique amino sugar, 4-amino-4,6-dideoxy-L-talose, which have not been hitherto found in the phleomycin-bleomycin group of antibiotics . In addition tallysomycin A has an additional amino acid, L-beta-lysine, and thus a longer peptide chain than bleomycin or tallysomycin B . Tallysomycins A and B have the same terminal amine moiety, spermidine. Gann, 1977 Oct, 68(5), 685 - 90 Antitumor activity of new anthracycline antibiotics, aclacinomycin-A and its analogs, and their toxicity; Hori S et al.; New anthracycline antibiotics have been isolated from the culture of Streptomyces galilaeus MA144-M1 . Among 14 anthracycline compounds, aclacinomycin-A showed the strongest activity in inhibiting leukemia L-1210 and had lower toxicity than others . Antitumor activity of aclacinomycin-A against leukemia L-1210 and P-388, solid sarcoma-180, and lymphosarcoma 6C3HED was examined in comparison with adriamycin and daunomycin . Aclacinomycin-A showed the same degree of activity against leukemia L-1210 and P-388, when administered intraperitoneally, as daunomycin and somewhat less than adriamycin . In oral administration, aclacinomycin-A also exhibited a significant activity on leukemia L-1210 . The degree of inhibition of the growth of sarcoma-180 and 6C3HED lymphosarcoma transplanted subcutaneously by aclacinomycin-A was almost the same as that of adriamycin and daunomycin, although the optimal dose was about twice more than adriamycin . Acute cardiotoxicity of aclacinomycin-A by a test using hamsters was more than 10 times lower than that of adriamycin. J Antibiot (Tokyo), 1977 Oct, 30(10), 806 - 10 The strobilurins--new antifungal antibiotics from the basidiomycete Strobilurus tenacellus; Anke T et al.; The strobilurins are two antifungal antibiotics which were isolated from the mycelium of Strobilurus tenacellus strain No . 21602 . The strobilurins A and B are highly active against yeasts and filamentous fungi . In vitro antitumor activity was tested using cells of the ascitic form of EHRLICH carcinoma . The strobilurins strongly inhibited the incorporation of radioactive leucine, uridine, and thymidine into the acid-insoluble fraction of cells (protein, RNA, and DNA) . The molecular formulas as determined by high resolution mass spectrometry are C16H18O3 for strobilurin A and C17H19C1O4 for strobilurin B. J Antibiot (Tokyo), 1977 Oct, 30(10), 819 - 28 Studies on the ionophorous antibiotics . XI . The artifacts and the degradation products of lysocellin; Koenuma M et al.; Lysocellin is a new polyether antibiotic produced by Streptomyces cacaoi var . asoensis and is characterized as a broad spectrum ionophore having a higher complexation affinity for divalent cations than for monovalents and also having an ability to transport biological amines . The structures of two artifacts designated L1 and M1 have been elucidated based on spectral evidence, and the formation mechanism of these compounds was discussed with respect to the reactivity of the antibiotic . In addition, a number of degradation and modified products were prepared in order to examine their biological activity and to utilize as the model compounds for 13C-NMR assignment. Pathol Biol (Paris), 1977 Oct, 25(8), 541 - 6 {Study of antibiotic sensitivity in 34 strains of large colony mycoplasma (author's transl)}; Laborde M; The application of Steer's technic to large colony mycoplasma for the study of antibiotic sensitivities, permitted us to compare the activity of various molecules inhibiting protein synthesis . Among large colony mycoplasmas, only mycoplasma pneumoniae is sensitive to erythromycin but we have already isolated a strain resistant at 400 microgram/ml . This should be remembered during treatment of mycoplasma pneumoniae infections . This species always remains sensitive to tetracycline . Among the latter, doxycyclin and minocyclin are preferred, firstly for their greater efficacy in vitro and secondly their better pharmacodynamic criteria . Gentamicin, tobramycin and chloramphenicol are also active in vitro . No trial in vivo has been carried out. Arch Surg, 1977 Oct, 112(10), 1240 - 4 Wound infection and topical antibiotics: the surgeon's dilemma; Halasz NA; The topical use of antibiotics in surgical wounds is critically reviewed and analyzed . Thirteen experimental and 19 clinical reports are included in this review . Prospective and retrospective clinical studies have been separated . The analysis evaluated clean vs contaminated/dirty wounds, as well as the effects of various antibiotics and combinations . The conclusion reached on the basis of the experimental and clinical data is that the application of carefully selected topical antibiotics to surgical wounds, particularly those that represent a high risk for the development of wound infection, can be expected to diminish the incidence of this complication in a significant fashion. Arch Dermatol, 1977 Oct, 113(10), 1378 - 9 Systemic antibiotic therapy of secondary infected dermatitis; Eaglstein WH et al.; Systemic cloxacillin therapy of secondarily infected dermatitis cloxacillin therapy become apparent produces a significant increase in healing when compared to a placebo . The effects of systemic after five days of treatment . A single pretreatment culture was not helpful in directing therapy. South Med J, 1977 Oct, 70 Suppl 1, 50 - 5 Prophylactic antibiotics in elective orthopedic surgery: a prospective study of 1,591 cases; Pavel A et al.; A double-blind prospective study involving 1,591 clean orthopedic surgical procedures was done to test the effectiveness of preoperative and intraoperative antibiotics in reducing the postoperative infection rate . The antibiotic and placebo groups were analyzed carefully for factors known to predispose to infection . Several minor exceptions were noted, but generally the antibiotic and placebo groups were comparable with regard to these factors . A decrease in overall postoperative infection rate from 5.0% in the placebo group to 2.8% in the antibiotic group was found . In specific areas such as the hip and spine a much greater reduction in postoperative wound infections occurred than in the group as a whole. J Thorac Cardiovasc Surg, 1977 Oct, 74(4), 528 - 36 Prophylactic antibiotics in the treatment of penetrating chest wounds . A prospective double-blind study; Grover FL et al.; Considerable controversy exists as to whether or not antibiotics should be administered "prophylactically" to patients with penetrating chest trauma . No prospective study of this problem has been reported . Therefore, 75 patients with isolated, penetrating chest injury were randomized prospectively in a double-blind study . Group A patients (38 patients) were given 300 mg . of clindamycin phosphate every 6 hours, beginning with admission and lasting until 1 day following chest tube removal or for 5 days, whichever was shorter . Group B patients (37 patients) were given a placebo on the same schedule . The patients' hospital course, fever, white blood count, culture data, and roentgenograms were recorded serially . Clindamycin-treated patients had a significantly lower incidence of radiographic pneumonia, less fever, and a lower incidence of positive pleural and wound cultures . They acquired empyema less frequently, required fewer operations, and had a shorter period of hospitalization . Antibiotics may be useful, therefore, as adjunctive therapy in the management of penetrating chest trauma. Ophthalmic Surg, 1977 Oct, 8(5), 44 - 8 Preoperative topical antibiotics and lash trimming in cataract surgery; Perry LD et al.; Fifty patients admitted for cataract extraction had their lids and conjunctive cultured two days preoperatively, on the morning of surgery, and on each of the first four postoperative mornings . Multiple topical preoperative antibiotics given for forty-eight hours before surgery produced a marked reduction in the periocular bacterial flora, an effect which persisted throughout the postoperative period . Lash trimming prior to surgery did not alter the periocular bacterial flora present on the morning of surgery or at any time during the first four postoperative days . While multiple preoperative topical antibiotics may reduce the incidence of postoperative endophthalmitis through suppression of periocular bacterial flora, no such role can be postulated for lash trimming. J Oral Surg, 1977 Oct, 35(10), 823 - 7 Surgical treatment of chronic osteomyelitis of the mandible resistant to intraarterial infusion of antibiotics: report of case; Nakajima T et al.; A 47-year-old man with chronic osteomyelitis of the mandible is described . The patient had frequent episodes of acute and subacute exacerbation at varying intervals for a period of six years in spite of extended antibiotic therapy . Intraarterial infusion of antibiotics through the superficial temporal artery also failed to cause any improvement . He was finally treated successfully by surgical intervention. J Antibiot (Tokyo), 1977 Oct, 30(10), 829 - 35 Studies on the ionophorous antibiotics . XII . Effects of ionophore lysocellin on cation distribution and respiration in mitochondria; Mitani M et al.; The effects of the ionophore lysocellin on the movements of Ca2+, Mg2+ and alkali metal cations and its effect on energy utilization by rat liver mitochondria have been investigated . At a concentration of 0.05 micrometer, lysocellin induced dissociation of membrane-bound calcium, and an apparent steady state was established across the inner membrane between energy-linked calcium accumulation and the ionophore-induced depletion of calcium . No detectable efflux of intramitochondrial Ca2+ and Mg2+ was induced by 0.05 micrometer lysocellin, but the uptake of exogenously added calcium was significantly inhibited . The ionophore augmented Mg2+ release from mitochondria induced by Ca2+ addition and also caused rapid release of K+ from mitochondria preloaded with K+ by valinomycin or monazomycin . High levels (0.5 approximately 10 micrometer of lysocellin caused massive depletion of endogenous Ca2+, Mg2+ and K+ from mitochondria, resulting in disruption of mitochondrial functions including release of state 4 respiration, stimulation of ATPase and inhibition of ADP- or DNP-stimulated respiration . Structure-activity studies with chemically modified compounds of lysocellin indicated the important role of terminal carboxylic acid and C21 hydroxyl function in the activity of the ionophore, and there is a good correlation between the effect of lysocellin on mitochondrial cation movements and its ability to complex with cations determined in an organic solvent-water two-phase partition system. J Antibiot (Tokyo), 1977 Oct, 30(10), 870 - 8 Amplifications of phleomycin and bleomycin-induced antibiotic activity in Escherichia coli by aromatic cationic compounds; Grigg GW et al.; A wide range of aromatic compounds has been shown to amplify phleomycin-induced cell killing in Escherichia coli . They include acridines, acridinium chlorides, dihydroanthracenes, anthracenes, dianthracenes, phenanthridinium salts, phenazinium chlorides, phenoxazones, triphenyl methane dyes, benzoquinolizinium chloride, diphenylmethane derivatives, stilbene and diphenyl derivatives . Low concentrations of these amplifiers also amplified the DNA breakage and degradation effects of phleomycin . The minimum structural specification for activity as an amplifying agent is suggested . A representative sample of compounds effective as amplifiers of phleomycin also amplified the antibiotic effects of bleomycins B4 and B6 . The amplifiers described are known to vary in their ability to penetrate and accumulate in different organisms or tissues . This suggests the possibility of developing a series of antibiotic regimes using these amplifiers (or the large number of derivative compounds also likely to be active) where the therapeutic index is determined by the properties of the amplifier chosen rather than of the phleomycin or the bleomycin. Nouv Presse Med, 1977 Sep 17, 6(30), 2677 - 80 {The nephrotoxic potential of cefalotin-aminoside antibiotic combinations (author's transl)}; Carbon C et al.; The combined study of animal experimental findings and clinical trials indicates the minimal effect on renal function of a combination of Cefalotin with aminoglycosides . Nevertheless, whilst the published cases of renal insufficiency are often difficult to analyse with regard to the exclusive responsibility of antibiotic therapy, it seems that strict attention to dose and frequency of administration is essential when this combination is prescribed and that regular surveillance of renal function is necessary, above all with prolonged treatment . The renal toxicity of aminoglycosides more recent than Gentamicin has not yet been fully explored, the same applying to their use in association with Cefalotin. Experientia, 1977 Sep 15, 33(9), 1212 - 3 Effects of the antibiotic netropsin on mouse ascites tumour chromosomes in vitro; Wobus AM et al.; The antibiotic netropsin was found to induce an increase of the aberration frequency of up to 10% and a decondensation and elongation of centromeric regions of the chromosomes in mouse ascites tumour cells cultivated in vitro. N Z Med J, 1977 Sep 14, 86(595), 221 - 3 Cholestyramine in the treatment of antibiotic associated pseudomembranous colitis: a case report; Sherry E et al.; A patient with antibiotic associated pseudomembranous colitis (A-PMC) is described in whom there was a dramatic response to the administration of cholestyramine . Although it is not clear why cholestyramine should be beneficial, its use should be considered whenever the diagnosis of pseudomembranous colitis is entertained. Acta Chir Belg, 1977 Sep-Oct, 76(5), 475 - 80 {Controlled study of oral administration of antibiotics in the preparation of digestive surgery (author's transl)}; Mendes da Costa P et al.; Between November 30, 1971 and March 15, 1976, 46 patients underwent surgery on the colon or rectum . They were randomized into 2 groups, one receiving a mechanical preparation together with lincomycline, neomycine, polymyxine, kanamycine, bacitracine and nystatine, the other a mechanical preparation alone . Analysis of results reveals no statistically significant difference in the frequency of infections, neither local (11/24 with antibiotics vis 13/22 without; chi2 = 0.25) neither general (16/24 and 9/22; chi2 = 0.92) . Nor was the postoperative use of antibiotics for local or general infection different in the 2 groups . No influence of age or preoperative radio-therapy could be shown . This randomized trial suggests that there is little advantage in associating antibiotics to mechanical preparation before colorectal surgery . The authors contemplate a new randomized trial in high-risk patients suffering from cancer. Antibiotiki, 1977 Sep, 22(9), 825 - 9 {Toxicity and side effects of antibiotics in radiation sickness and during the use of aminothiol group radioprotective agents}; Lushnikova GA; It was shown in experiments on mice, rats and rabbits that resistance of animals in the state of acute radiation sickness to severe intoxication by aminoglycoside antibiotics, such as streptomycin, dihydrostreptomycin and monomycin did not significantly change . The exception was kanamycin the toxicity of which during the period of the acute state of radiation sickness increased by 30 per cent . The use of cystamine and merkamine before irradiation or their administration to non-irradiated animals resulted in lowering of the antibiotic tolerance by 1.5--2 times . The above aftereffects of the radioprotectors was observed within 3--12 days after their use and was most pronounced for the combination of cystamine and streptomycin . The acute toxicity of tetracyclines did not significantly differ at various stages of radiation disease and at the background of cystamine use . No significant cumulation of the toxicity of aminoglycoside antibiotics and tetracyclines or signs of adaptation in the healthy and irradiated animals was observed on prolong treatment with therapeutic doses . Cystamine had no effect on the tolerance of the antibiotics on their prolonged use. Antibiotiki, 1977 Sep, 22(9), 816 - 21 {Diagnosis of anaphylactic shock caused by antibiotics}; Donchenko VS et al.; A total of 277 cases with anaphylactic shock due to the use of various antibiotics were analyzed . Anaphylactic shock due to penicillin (38.2 per cent), streptomycin (19.8 per cent), combihation of streptomycin with penicillin (16.9 per cent) or bicillin (15.2 per cent) was most frequent . The causes of the diagnostic mistakes are shown and the clinical signs of the main typical form of the drug anaphylactic shock are descrifed . Four variants of atypical clinical picture of anaphylactic shock, i.e . hemodynamic (collaptoid), asphyctic, cerebral and abdominal were classified . Examples of diagnostic mistakes are presented . It was shown that the drug allergological anamnesis was not always considered in the therapeutic practice. Antibiotiki, 1977 Sep, 22(9), 794 - 7 {Some features of the side effects of antibiotics in bronchopulmonary diseases}; Zamotaev IP et al.; A total of 1838 cases treated with antibiotics were analyzed in a pulmonological clinic . The antibiotics were used because of acute pneumonia, exacerbated chronic pneumonia, active inflammatory processes in cases with infectious allergic bronchial asthma and other bronchopulmonary diseases . Levomycetin (21 per cent), benzylpenicillin (14 per cent), oletetrin, erythromycin, semi-synthetic penicillins, aminoglycosides and other antibiotics were used most often . The antibiotic side effects were registered in 1.4 per cent of the cases, the allergic complications being 4 times more frequent than toxico-metabolic complications . The main path for prevention of the antibiotic side effects was rational antibiotic therapy . The antibiotic choice should be guided by the following considerations: process localization, patient's age, causative agent species, its antibiotic sensitivity, antibiotic pharmacokinetic characteristics in the organism of the patient, character of the antibiotic side effects on the macroorganism. Antibiotiki, 1977 Sep, 22(9), 790 - 4 {Modern principles for studying the organotropic side effects caused by antibiotics}; Solov'ev VN; For prophylaxis of the organotropic side reactions in antibiotic therapy it is important to determine correlation between the drug blood level and the effect level . The study of this correlation under experimental conditions provides determination of the maximum permissible concentration of the antibiotic in the blood . When the antibiotic side effects are diagnosed in clinics it is advisable to determine as exact as possible the peculiar properties of the drug pharmacokinetics in the respective patients. Antibiotiki, 1977 Sep, 22(9), 781 - 9 {Antibiotics and the macroorganism (the causes and the mechanism of occurrence of side effects}; Navashin SM et al.; The main types of side reactions due to antibiotic therapy are described . The antibiotic groups most often being the cause of side reactions are presented . Dependence of the toxic (organotropic) effect of antibiotics on the therapy scheme, age and pathological changes in the mechanism of their excretion is indicated . The biochemical mechanisms of the side and selective effects of antibiotics are discussed. Antibiotiki, 1977 Sep, 22(9), 775 - 80 {Clinical and statistical analysis of the side effects and complications of antibiotic therapy}; Lopatin AS et al.; A total of 4936 side reactions and complications in 2311 patients subjected to antibiotic therapy were analyzed . The drug allergy was of the allergic nature in 79.9 per cent of the cases, in 6.03 per cent of the cases it was of the toxic nature and in 6.03 per cent of the cases the drug allergy had a toxico-allergic genesis . Dysbacterioses and candidoses were diagnosed in 7.22 per cent of the cases . The complications were lethal in 0.9 per cent of the patients . The complications due to the antibiotic therapy may be arranged in the following descending order: penicillin (51.56 per cent), tetracycline (18.03 per cent), streptomycin (11.5 per cent), levomycetin and sintomycin (11.07 per cent), macrolide antibiotics (5.43 per cent) . Affections of the skin and its appendages, nervous system and gastro-intestinal tract were most common . The penicillin side effects were characterized by more frequent skin allergic reactions amd neuro-psychic impairments . Tetracyclines caused more allergic reactions than it was usually considered . Streptomycin was characterized by high shockogenic properties, neurotoxicity and hematotoxicity . The toxic complications were most often caused by aminoglycosides . They were evident clinically from ototoxic and nephrotoxic reactions . General causes of complications due to antibiotic therapy are discussed. Ann Surg, 1977 Sep, 186(3), 251 - 9 Preoperative oral antibiotics reduce septic complications of colon operations: results of prospective, randomized, double-blind clinical study; Clarke JS et al.; The effectiveness of short-term, low-dose, preoperative oral administration of neomycin and erythromycin base combined with vigorous purgation in reducing the incidence of wound infections and other septic complications of elective colon and rectal operations has been studied in a prospective, randomized, double-blind, clinical trial . One hundred and sixteen patients completed the study; all received mechanical preparation; 56 received neomycin-erythromycin base while 60 received an identical appearing placebo . The two patient groups were comparable in age distribution, clinical diagnoses, associated systemic diseases, types of operation performed and similar clinical features . The overall rate of directly related septic complications was 43 per cent in the placebo group and 9% in the group receiving neomycin and erythromycin base . The wound infection rates were 35% in placebo and 9% in antibiotic treated patients . Oral administration of neomycin and erythromycin base together with vigorous mechanical cleansing reduces the risk of septic complications after elective colo-rectal operations. Mol Biol (Mosk), 1977 Sep-Oct, 11(5), 1079 - 89 {Use of the antibiotics actinomycin D and distamycin A to limit the action of restriction endonucleases and to map DNA}; Nosikov VV et al.; It is shown that distamycin A and actinomycin D protect the recognition sites of certain restriction endonucleases from the attack by these nucleases due to specific interaction of these antibiotics with double-stranded DNA . Distamycin A protects A-T containing sites and actinomycin G-C rich sites . Among Hind II recognition sites which have alternative structure (GTPyPuAC) distamycin A protects only Hpa I similar sites (GTTAAC) . It is shown with several restriction endonucleases that antibiotic action depends on the nucleotide sequences in the recognition sites and in their closest environment . Proper concentrations of antibiotic give rise to larger fragments . Use of both distamycin A and actinomycin D allows to obtain a set of overlapping fragments . The data obtained with various DNAs and restriction endonucleases allow to conclude that these antibiotics may be useful for DNA mapping and for preparation of large functional fragments of DNA. Vopr Med Khim, 1977 Sep-Oct, 23(5), 632 - 5 {Trypsin and lipase activity in the presence of antibiotics}; Geitman IIa et al.; Effect of penicillin, kanamycin and streptomycin on the proteolytic activity of trypsin using hemoglobin and casein as substrates as well as effect of these antibiotics and oxacilin, methycillin and tetracycline on the lipase activity were studied in vitro . Penicillin, kanamycin and streptomycin (5 mg, 20 mg and 80 mg of the antibiotic per 1 mg of trypsin, respectively) did not inhibit the proteolytic activity of the enzyme . Kanamycin slightly activated the trypsin activity in reaction with hemoglobin and streptomycin -- in reaction with casein . Penicillin, oxacillin and methycillin inhibited the lipase activity, when 80-100 mg of the antibiotics were used per 1 mg of the enzyme. Antibiotiki, 1977 Sep, 22(9), 807 - 9 {Detection of allergy to antibiotics in dermatology--venereology practice}; Lonshakov IuI et al.; A total of 205 stationary patients with and without drug disease were examined with the purpose of diagnosing allergy to the widely used antibiotics . The reaction of leucocytosis was used in the studies and the antibiotic concentration was increased up to 1 gamma/ml . Sufficiently high specificity of the reaction for diagnosis of the medicamentous allergy was determined . Increased sensitivity was most frequent to penicillins . Participation of biologically active substances, such as heparin and histamine in exacerbation reaction in syphilitic patients treated with penicillin was found . The most pronounced increase in the levels of these substances in the blood of the patients was observed 6 hours after the beginning of the treatment without any connection without any connection with the clinical signs of the exacerbation reaction. Antibiotiki, 1977 Sep, 22(9), 771 - 5 {Rational use of antibiotics is the basis of their effectiveness and safety}; Babaian EA; Many-year studies on the use of antibiotics in the general medical practice are summarized in the paper . The present trends in further improvement of the rational use of antibiotics are presented . It is shown that the present rational and safe antibiotic therapy is determined by 3 main factors: (1) choice of the drug with due regard for its pharmacological properties and spectrum, (2) isolation, identification and determination of the bacterial flora sensitivity to the antibiotic, (3) revealing or prevention of high sensitivity of the patients to the antibiotics chosen. Antibiotiki, 1977 Sep, 22(9), 821 - 4 {Nerve-blocking properties of antibiotics}; Berezhinskaia VV et al.; Comparative data on the neuroblocking activity of antibiotics of various groups in acute experiments on albino mice and narcotized cats are presented . It was found that according to the impairments in the neuro-muscle conductivity the drugs were arranged in the following descending order: polymyxin B, neomycin, gentamicin, streptomycin, lincomycin and kanamycin . The streptomycin derivatives were approximately 2 times less toxic than streptomycin . The problems of the mode of action of the antibiotics on conductivity of excitation in the neuro-muscle synapses are discussed. Antibiotiki, 1977 Sep, 22(9), 804 - 7 {Modern problems of drug allergy to antibiotics in the clinical aspects of skin and venereal diseases}; Soloshenko EN et al.; Allergic dermatoses induced by antibiotics amounted to 45.2 per cent of all determined drug reactions according to the data of the Kharkov Research Institute of Dermatology and Venerology . The data on the factors favouring development of the drug dermatoses are presented . Difficulties in differential diagnosis by means of clinical and laboratory methods are indicated . The modern immunological tests of etiological diagnosis of drug resistance and the results of studying non-specific reactivity in patients with medicamentous dermatoses were analyzed . The principles of therapy and prophylaxis are summarized. Z Gesamte Inn Med, 1977 Aug 1, 32(15), Suppl: 238 - 9 {Therapeutic results using combined antibiotic therapy in chronic carriers}; Horn M et al.; From 1969 to January 1976 82 chronic carriers underwent a sanitation treatment . This treatment consists in an antibiotic combination treatment with ampicillin and canamycin during 24 to 18 days, in which case possibly simultaneously the cholecystectomy is striven for . In chronic carriers of S . typhi in 37 cases the combined antibiotic-operative treatment led to the permanent success . In chronic carriers of S . paratyphi B 21 of 22 cases were present . In patients with condition after cholecystectomy in every case one failure was present . In purely conservative approach the coefficient of success was 50 and 78%. J Thorac Cardiovasc Surg, 1977 Aug, 74(2), 230 - 7 Isolated mitral replacement with stent-mounted antibiotic-treated aortic allograft valves; Heng MK et al.; The results of valve replacement with a stent-mounted antibiotic-treated aortic allograft valve are reported in 129 patients with isolated mitral valve disease . Of these patients, 70 per cent were in N.Y.H.A . Class IV . The hospital mortality rate was 3.9 percent . The cumulative complication-free rate at 5 years was only 37 percent as 21 percent died late, a further 15 percent were alive following reoperation, 4 percent had an embolic episode, 4 percent were alive with important incompetence, and 20 percent had unimportant incompetence . Proved valve failure was due mainly to detachment of the aortic wall remnant of the valve from the pillar of the rigid metal stent (16 percent incidence at 5 years) and methods for preventing this complication are discussed . Because of these complications the use of this device in the mitral position has been discontinued. Tohoku J Exp Med, 1977 Aug, 122(4), 403 - 4 Myroridin, a new peptide antibiotic from Myrothecium SP . 285F; Kondo S; Myroridin, a new basic peptide antibiotic was isolated from culture filtrate of a strain of Myrothecium, No . 285f . The present paper describes the production, isolation and characterization of this antibiotic. Antibiotiki, 1977 Aug, 22(8), 699 - 704 {Conjugation transfer of plasmid resistance to gentamycin and other antibiotics in clinical strains of Ps . aeruginosa}; Moroz AF et al.; A possibility of conjugation transfer of the markers of the plasmid resistance to gentamicin and other antibiotics from 10 clinical strains of Ps . aeruginosa, isolated from burn patients to the recipient strain of Ps . aeruginosa PTO 629 Rfr was shown . The marker of gentamicin resistance was transferred to 100 out of 110 of the exconjugants, i.e . 86.2 per cent . The rate of the conjugation transfer in the crosses between the clincal strains of Ps . aeruginosa and the recipient strain PTO 629 Rfr with respect to the gentamicin marker was about 10--7 . The plasmid resistance markers in the clincal strains Ps . aeruginosa were transferred in various combinations . Transfer of the markers of resistance to streptomycin, carbenicillin, neomycin and combinations Sm, Nm and Sm, Nm, Cm was not achieved. South Med J, 1977 Aug, 70(8), 1017 - 9 Antibiotic agranulocytosis: association with cephalothin and carbenicillin; Allo M et al.; A 65-year-old woman developed agranulocytosis on two separate occasions following prophylactic administration of antibiotics before cardiac surgery . In the first leukopenic episode, large doses of cephalosporin derivatives were the only drugs implicated, and in the second, carbenicillin was believed responsible . Life-threatening septicemia occurred with Pseduomonas aeruginosa and later with Escherichia coli . Erythrocytes, platelets, and lymphocytes were not affected during these granulocytopenias . Bone marrow examination revealed an arrest of maturation in the granulocytic series . Review of the hematologic complications of cephalosporins, particularly agranulocytosis, suggests an interesting association between carbenicillin-induced neutropenia and previous administration of cephalosporins. Acta Pathol Microbiol Scand {C}, 1977 Aug, 85C(4), 277 - 83 In vitro activating properties of polyene antibiotics for murine lymphocytes; Hammarstrom L et al.; The effect of four polyene antibiotics, Candicidin, Etruscomycin, Filipin and Pimaricin upon mouse lymphocytes was studied . Polyene antibiotics are known to form aqueous pores in the cell membranes inducing known anion or cation selective fluxes . Candicidin was capable of inducing marked DNA-synthesis and polyclonal antibody production when added to normal spleen cells . Etruscomycin and Pimaricin showed a weak inconsistent DNA synthetic stimulatory effect, whereas Filipin was found to be totally uneffective . The stimulating property of Candicidin was also demonstrated on spleen cells from nude mice whereas there was no effect on cortisone resistant thymocytes or spleen cells passed through a nylon fibre column . Thus we conclude that Candicidin is a PBA for mouse lymphocytes . We have previously reported that the two anionselective polyenes, Nystatin and Amphotericin B, are polyclonal B-cell activators for mouse lymphocytes and in this paper the possible mechanism of triggering is further discussed. Biochim Biophys Acta, 1977 Jul 20, 488(1), 97 - 101 Time-dependent, irreversible inhibition of 3-hydroxy-3-methylglutaryl-coenzyme A reductase by the antibiotic citrinin; Tanzawa K et al.; The inhibition of 3-hydroxy-3-methylglutaryl-CoA reductase by citrinin, an antibiotic, has been studied . The inhibition was the mixed type with respect to 3-hydroxy-3-methylglutaryl-CoA and non-competitive with respect to NADPH . When the enzyme was preincubated with citrinin prior to enzyme assay, however, it caused a time-dependent, irreversible inhibition, possibly by binding to a site distinct from the active center on the enzyme protein. Lancet, 1977 Jul 2, 2(8027), 4 - 8 Prophylactic systemic antibiotics in colorectal surgery; Feathers RS et al.; The prophylactic value of gentamicin combined with either lincomycin or metronidazole in 52 patients undergoing colorectal surgery was investigated . The results confirmed the value of this practice . In a control group, the sepsis-rate was 48% with 1 death attributable to sepsis, compared with a sepsis-rate of 4% in the treated group . The combination of gentamicin and lincomycin was effective against sepsis but pseudomembranous colitis developed in 2 of the 14 patients treated with this combination of drugs . Lincomycin was discontinued, and when metronidazole was substituted the results were equally good and there were no toxic side-effects. Vopr Pitan, 1977 Jul-Aug, (4), 17 - 21 {Effect of antibiotics on cholesterol metabolism under conditions of a varying protein content in the diet}; Sheveleva SA et al.; In tests on rats subject to study were the effects of native tetracycline, thermally treated and used in doses of 100 mg/kg, of tetracycline in a dose of 20 mg/kg and of penicillin on the secretion of bile and generation of free and conjugated bile acids and cholesterol, as well as upon the cholesterol content in the blood and liver tissues with complete and protein-deficient rations . With complete ration tetracycline in its native and thermally treated forms provoked a fall in the cholesterol content in the bile and hepatic tissue, a rise in percentage of free bile acids and a decline of the tauroconjugates percentage . With a protein-low ration tetracycline called for an increased concentration of the bile cholesterol with simultaneously increasing concentration of cholic acid. Acta Otolaryngol, 1977 Jul-Aug, 84(1-2), 57 - 64 Comparative surface studies of ototoxic effects of various aminoglycoside antibiotics on the organ of Corti in the guinea pig . A scanning electron microscopic study; Theopold HM; It was the purpose of this study to establish criteria for use in comparing the toxic effects of aminoglycosid antibiotics on the organ of Corti by means of scanning electron microscopy . Amikacin, Tobramycin and Gentamicin were administered twice a day subcutaneously for 10 days to healthy guinea pigs . One group of animals was sacrificed 1 day after completion of the treatment; the other group was allowed to survive 22 days . Depending upon the dosage of the administered drug, Amikacin (150 mg per kg body weight daily, corresponding to 10 times an average recommended human dose) caused pronounced outer hair cell damage even 1 day after the treatment was stopped . At this time Gentamicin and Tobramycin (150 mg per kg body weight daily, corresponding to 50 times an average human dose) showed less damage . After 22 days' survival, late toxic effects were found mainly in Gentamicin- and Tobramycin-treated animals . After 3 weeks, nearly total outer hair cell loss was found in the basal coil, while the 2nd and 3rd coils were often less severely damaged . At this time Amikacin-treated animals showed severe damage in all coils . 300 mg per kg body weight Amikacin (i.e . 20 times the average human dose) showed about the same toxic effect on sensory cells of the guinea pig as did 150 mg Gentamicin or Tobramycin per kg body weight . We are conscious of the fact that there are problems in correlating the weight of a drug and its probable toxic effect . In comparative animal experiments we consider it useful to standardize the time of exposure, the amount of drug administered (e.g . related to the human dose) and the survival time. Neurochirurgia (Stuttg), 1977 Jul, 20(4), 123 - 31 {Investigation of the c . s . fluid levels of two newer antibiotics; cefazolin and sisomicin (author's transl)}; Friedrich H et al.; In ten patients continuous estimations of the C.S.F . and serum levels were performed after the administration of a Cephalosporin derivative (Cefazolin - 4 cases) and a new alpha-amino-glycoside antibiotic (Sisomicin - 6 cases) . After the evaluation of the results some doubts must be cast on the value of both these antibiotics for the treatment of meningitis or for per-operative chemo-prophylaxis in neurosurgical procedures . The values found were compared with those well-known in the literature, regarding the cephalosporins and the alpha-amino-glycoside Gentamycin. J Antibiot (Tokyo), 1977 Jul, 30(7), 552 - 63 Fortimicins A and B, new aminoglycoside antibiotics . III . Structural identification; Egan RS et al.; The structures of fortimicins A and B have been determined by PMR, CMR, mass spectra and CD combined with chemical degradations . Both antibiotics are pseudodisaccharides and incorporate a novel aminocyclitol, fortamine . In contrast to the diaminocyclitol moieties of known aminoglycosides, fortamine is a 1,4-diamine, contains both N- and O-methyl groups and possesses chiro stereochemistry . Both antibiotics are glycosides of 6-epi-purpurosamine B, but fortimicin A differs from fortimicin B by being a glycyl amide. Clin Pharmacol Ther, 1977 Jul, 22(1), 1 - 6 Antibiotic-associated colitis; Miller RR et al.; Among 26,294 hospitalized patients monitored by the Boston Collaborative Drug Surveillance Program (BCDSP), 8,948 (34%) received at least one antibiotic, and none were diagnosed as having drug-induced colitis to in-hospital antibiotic exposure . Seven patients who had taken antibiotics as outpatients, however, were admitted with antibiotic-associated colitis . Six of these patients had taken lincomycin prior to the onset of symptoms; one had taken ampicillin . Six of the patients were hospitalized at a New Zealand hospital and one at a hospital in Canada . The five patients with lincomycin-associated colitis at the New Zealand hospital were admitted over an 11-month period . Severe colitis due to antibiotics has been a rare event in the BCDSP experience, especially in the United States. Clin Chem, 1977 Jul, 23(7), 1340 - 2 Positive interference with the Jaffé reaction by cephalosporin antibiotics; Swain RR et al.; Cephaloglycin, cephalothin, cephaloridine, cefoxitin, and cephacetrile are cephalosporin antibiotics that react with alkaline picrate solution to give a creatinine-like response . The mechanism of this reaction is not known, and several structurally similar compounds do not react under these same conditions . Because large quantities of a cephalosporin antibiotic may be administered to a patient with limited ability to excrete the drug (as occurs with compromised renal function), the magnitude of this interference can be appreciable . It does not appear possible to avoid the cephalosporin-caused interference by the use of "kinetic" creatinine methods. Anesth Analg, 1977 Jul-Aug, 56(4), 515 - 21 Interaction of halothane and antibiotics on isometric contractions on rat-heart muscle; Sohn YZ et al.; Halothane (H), kanamycin (KM), streptomycin (SM), and chloramphenicol (CM) had direct negative inotropic effects on isometric contractions of isolated rat-heart muscles . Potassium penicillin-G did not show any significant changes in isometric contractions . The depression produced by these antibiotics was characterized by an abrupt onset, rapid progression, and rapid complete recovery, which suggests direct physicochemical rather than metabolic effects . On the other hand, the depression produced by H progressed slowly . When KM, SM, or CM were combined with H, there was a greater depression in isometric contractions than seen in the absence of H, suggesting that the innate characteristics of the antibiotics are augmented when any of them is administered together with halothane. Mod Vet Pract, 1977 Jul, 58(7), 594 - 8 Toxicity of aminoglycoside antibiotics; Clark CH; In cats, aminoclycosides cause vestibular damage followed in a few days by renal damage . The reverse is true in the dog, except that streptomycin causes vestibular damage prior to renal damage . To avoid toxicities, therapeutic doses of aminoglycosides should not be given longer than a week and they should be given cautiously in animals with renal impairment . Failure of the kidneys to eliminate aminoglycosides will result in very high blood levels, even with therapeutic doses, that can cause further renal and vestibular damage . The oral administration of aminoglycosides is seldom dangerous when normal therapeutic doses are employed . Although it is remote, the possibility exists that animals with renal impairment and intestinal obstruction may become intoxicated . Kanamycin is less nephrotoxic to dogs than neomycin and it is less destructive to the auditory nerve than vestibular damage than streptomycin . Gentamicin in cats is twice as toxic to the vestibular apparatus as streptomycin and more toxic to the cochlea than streptomycin or dihydrostreptomycin . Neomycin is more toxic than kanamycin, gentamicin, and streptomycin to both cats and dogs . Amikacin causes renal damage in dogs similar to other aminoglycosides . It also causes vestibular damage. J Antibiot (Tokyo), 1977 Jul, 30(7), 571 - 5 The isolation and structure elucidation of macrocyclic lactone antibiotic, A26771B; Michel KH et al.; The isolation, biological properties and structure elucidation of a sixteen-membered macrocyclic lactone antibiotic, designated A26771B (1), obtained from Penicillium turbatum are discussed. Can J Comp Med, 1977 Jul, 41(3), 251 - 6 Hypocalcemic effect of aminoglycoside antibiotics in the dairy cow; Crawford LM et al.; The effect of the parenteral administration of aminoglycoside antibiotics on the blood calcium concentration in dairy cows was investigated . Gentamicin was tested in vitro in blood drawn from cows, dihydrostreptomycin was tested in nonlactating cows and neomycin was tested in postpartum cows . The total and bound calcium fractions were significantly reduced by all three antibiotics . No change occurred in the unbound calcium fractions . Caution is advised in the use of these drugs in postpartum cows, especially those with a history of milk fever. Res Commun Chem Pathol Pharmacol, 1977 Jul, 17(3), 547 - 50 Metal ion catalyzed oxidation of the antibiotic rifampicin; Buss WC et al.; The metal ions Cu++, Mn++ and Co+++, but not Ca++, Fe+++, K+, La+++, Mg++, Na+, Sr++ or Zn++ catalyzed the oxidation of rifampicin from the naphthohydroquinone to the naphthoquinone form . This reaction was pH dependent, and occurred at neutral or basic pH more rapidly than at acidic pH . Mn++ catalyzed the most rapid oxidation, followed by Cu++ and then Co+++ . Rifampicin oxidation was metal ion dependent and complete oxidation occurred at metal ion concentrations below stoichiometric values . Initial rate studies suggest that the oxidation mechanism is complex. J Antibiot (Tokyo), 1977 Jul, 30(7), 597 - 603 Aminoglycoside nephrotoxicity . I . Effects of aminoglycoside antibiotics on iodohippurate accumulation in rabbit renal cortical slices; Dahlager J et al.; The effects of aminoglycoside antibiotics on the accumulation of O-125I-hippurate (OIH) in rabbit renal cortical slices were assessed in an attempt to establish an in vitro model for aminoglycoside nephrotoxicity . Accumulation of OIH was measured after incubation of cortex slices in media containing aminoglycosides in different concentrations . All aminoglycosides depressed OIH accumulation in the following minimum concentrations: Dihydrostreptomycin and kanamycin, 2,000 microgram/ml (P less than 0.01); streptomycin and neomycin, 1,000 microgram/ml (P less than 0.05 and P less than 0.01); amikacin and tobramycin, 300 microgram/ml (P less than 0.05); gentamicin, 100 microgram/ml (P less than 0.05) . A concentration of 2,000 microgram/ml caused the following reduction in OIH accumulation: Dihydrostreptomycin, 19.3%; streptomycin, 28.9%; kanamycin, 23.8%; neomycin, 62.5%; gentamicin, 68.0%; amikacin and tobramycin, 100% . Changes in pH of the incubation media after addition of aminoglycosides were only partially responsible for the observed depression of OIH accu