Antibiotics

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 accumulation and there was no evidence of substrate competition between aminoglycosides and OIH . The in vitro model described here appears to be inadequate as a sole predictor of aminoglycoside nephrotoxicity, but may provide a supplementary tool in the investigation of aminoglycoside proximal tubular cell toxicity.

Biochemistry, 1977 Jun 28, 16(13), 2860 - 6
Studies on the biosynthesis of 16-membered macrolide antibiotics using carbon-13 nuclear magnetic resonance spectroscopy; Omura S et al.; The origin of the skeletal carbons in the lactone ring of 16-membered macrolide antiobiotics has been studied . 13C-labeled antibiotics leucomycin and tylosin, have been obtained from the culture broth of Streptomyces kitasatoensis 66-14-3 and Streptomyces fradiae C-373, respectively in the presence of appropriate 13C-labeled precursors, and 13C NMR spectra of the antibiotics thus obtained have been measured . It was shown that the aglycone of leucomycin A3 is derived from five acetates, one propionate, one butyrate, and an unknown precursor corresponding to two carbons . The formyl carbon which is characteristic of the basic 16-membered macrolides orginates from C-4 butyrate . On the other hand, the aglycone of tylosin is formed from two acetates, five propionates and one butyrate . Butyric acid and ethylmalonic acid are metabolized to propionyl-CoA or methylmolonyl-CoA through a pathway involving methylmalonyl-CoA mutase, and subsequently incorporated into the lactone ring of tylosin.

JAMA, 1977 Jun 27, 237(26), 2819 - 22
Antibiotic use at Duke University Medical Center; Castle M et al.; A study of antibiotic use at Duke University Medical Center in June 1973 showed that 34.2% of all patients received antibiotics (43.6% surgical, 21.4% medical patients) . Cephalothins were most frequently ordered for surgical patients, ampicillin sodium and penicillin G or penicillin V with potassium for other patients . A retrospective analysis of 50 randomly selected patients, according to the Kunin's categories of use, showed 64% of total antibiotic therapy as not indicated or inappropriately administered in terms of drug or dosage . These results are similar to previous reports of antibiotic surveillance and further establish the need for continuing education of prescribing physicians.

Jpn J Antibiot, 1977 Jun, 30(6), 362 - 85
{The general pharmacological actions of KW-1062, a new aminoglycoside antibiotic (author's transl)}; Hashimoto T et al.; The general pharmacological actions of KW-1062 were investigated in order to estimate the effects on the host animals . KW-1062 showed little or no effect on the central nervous system, cardiovascular system, smooth muscle, skeletal muscle, hemolysis, blood coagulation, dermal tissue permeability and antigenicity tests at high doses . KW-1062 showed urinative effect and ototoxicity . But ototoxicity of KW-1062 was less potent than that of gentamicin . KW-1062 has been proved to have a safety margin wider than that of other aminoglycoside antibiotics.

J Antibiot (Tokyo), 1977 Jun, 30(6), 488 - 93
Biosynthetic studies on the macrolide antibiotic turimycin using 14C-labeled precursors; Gersch D et al.; Using a strain of Streptomyces hygroscopicus JA 6599 several 14C-compounds were investigates as potential precursors of the macrolide antibiotic turimycin followed by partial degradation to localize the radioactivity . L-Methionine-14C-methyl and n-butyrate-1-14C were incorporated exclusively and in a specific manner . The incorporation ratios were dependent on the addition time of the precursors . Studies of the incorporation of acylmycaroses and demycarosyl turimycin into the antibiotic are also reported.

J Antibiot (Tokyo), 1977 Jun, 30(6), 450 - 4
Macrolide antibiotics M-4365 produced by Micromonospora . II . Chemical structures; Kinumaki A et al.; By physiochemical analyses and chemical procedures, the structures of a series of basic 16-membered macrolide antibiotics, M-4365, A1, A2, A3, G1, G2 and G3 were elucidated, and it was found that M-4365 A1, G1 and G2 were novel, while M-4365 A2, A3 and G3 were identical with rosamicin, juvenimicins A4 and B1, respectively.

Isr J Med Sci, 1977 Jun, 13(6), 549 - 56
Pattern of prophylactic use of antibiotics in six surgical departments of a teaching hospital in Jerusalem; Michel J et al.; The prophylactic use of antibiotics for various surgical procedures was studied in six surgical departments of the Hadassah University Hospital over an 18-month period between January 1972 and June 1973 . A total of 7,339 patients was discharged from the six departments during this period . Antibiotics had been used prophylactically in 17.7% of these patients and in 20.4% of the 6,313 patients in whom there was no evidence of infection on admission . The rate of prophylactic use varied from 12.8 to 47.8% in different departments . Different prophylactic regimes were used in the various departments, but there was a tendency for the same regime to be used within one department, irrespective of the nature of the surgical procedure . The antibiotics were usually started postoperatively . The duration of the prophylactic courses varied but there was a general tendency to continue for more than five days, often up to 10 or more days . The frequency of use seemed to be related to the presence of factors regarded as carrying a high risk of infection, such as advanced age, operation through a contaminated field and the presence of malignancy . The association between prophylactic use and subsequent wound infection was examined . The importance of continuous surveillance of the prophylactic use of antibiotics and the role of the infection-control unit in this surveillance is stressed.

Antibiotiki, 1977 Jun, 22(6), 553 - 7
{Effect of the anthracycline antineoplastic antibiotics, rubomycin and carminomycin, on the glycogen and nucleic acid content in the myocardium of white mice}; Shepelevtseva NG; The effect of 2 anthracycline antibiotics, i.e . rubomycin and karminomycin on the content of glycogen, RNA and DNA in the cardiac muscle of albino mice was studied on their five-fold intravenous administration once every 5 days in equieffect doses by the lethal outcome . It was found that under the effect of the above antibiotics accumulation of glycogen in the cardiac muscle of mice took place, this was most pronounced in the animals treated with karminomycin in doses of 2.15 mg/kg . A decrease in the absolute content of RNA and DNA in the mouse heart after the first 4 administrations and in the ratio of RNA to DNA was observed as compared to the analogous values in the control animals at the account of a more intensive decrease in the content of RNA than that of DNA.

Antibiotiki, 1977 Jun, 22(6), 516 - 8
{Antibiotic sensitivity of Staph . aureus strains isolated from the upper respiratory tracts of healthy carriers}; Ternovskaia LN; Sensitivity of 1004 cultures of Staph . aureus isolated from the upper respiratory tracts of the staff of a maternity hospital was studied by the method of serial dilutions in agar with respect to 11 antibiotics . It was found that 61.9, 39.5 and 16.5 per cent of the isolates were resistant to benzylpenicillin, tetracycline and levomycetin respectively . Most of the cultures were sensitive to streptomycin and oleandomycin . The cultures of Staph . aureus isolated from the staff were sensitive to low doses of kanamycin, oxacillin and lincomycin . Most of the isolates were inhibited only by high doses of methicillin, ampicillin, ristomycin and cephaloridin.

Antibiotiki, 1977 Jun, 22(6), 483 - 6
{Formation of a new antibiotic, nocamycin, by a culture of Nocardiopsis syringae sp . nov.}; Gauze GF et al.; A culture of a new actinomycetous species, Nocardiopsis syrinage was isolated from a soil sample . The antibiotic produced by it was named nocamycin . It accumulated in the culture fluid on cultivation of the organism in a nutrient medium containing soybean meal, glycerin, sodium chloride and calcium carbonate . Crystalline nocamycin had an antitumor effect . In inhibited by 72--73 per cent the development of an intraperitoneally implanted lymphadenosis of strain NK/LI in mice.

J Bacteriol, 1977 Jun, 130(3), 1357 - 63
Methanococcus vannielii: ultrastructure and sensitivity to detergents and antibiotics; Jones JB et al.; Methanococcus vannielii is a strictly anaerobic motile coccus that possesses a tuft of flagellae . The cells are markedly sensitive to mechanical stress and are readily lysed by detergents, but the organism grows normally in media of low ionic strength . The absence of a typical cell wall, further suggested by resistance of M . vannielii to penicillin, cycloserine, and vancomycin, was confirmed by ultrastructural studies . Electron micrographs showed that the cell envelope lacks a peptidoglycan layer . On the outer surface there is a regular array of subunits similar to those of the glycoprotein envelopes of the halobacteria . However, the M . vannielii cell envelope, unlike those of the holobacteria, is unable to maintain a definite shape, and a high salt concentration is not required for its integrity.

Antibiotiki, 1977 Jun, 22(6), 544 - 52
{Effect of antibiotics on the structure and function of the ovaries}; Kharitonova AM et al.; Streptomycin, penicillin, levomycetin, florimycin, cycloserin, erythromycin, sekazin, novobiocin, tetracyclines and neomycins had a stimulating effect on the sexual organs of the tests animals during the 1st decade of their administration . With long-term use some of the drugs induced dystrophic changes in the ovary . The signs of stimulation in the ovary were evident from increased activity of the oxidation-reduction enzymes in the inner membrane of the follicles and the interstitial cells of the stroma, as well as in an increase in the number of the maturating follicles . With long-term long use of erythromycin, sekasin or novobiocin, disappearance of the primordial follicles, an increase in the number of the atretic follicles and death of the ovocytes in the mature follicles were observed in the ovary.

Vet Med (Praha), 1977 Jun, 22(6), 377 - 84
{Effect of non-antibiotic stimulators on laboratory rats}; Sykora I; The stimulative effect of Carbadox, Nitrovin and Glypondin substances was tested on juvenile rats . A stimulative effect relative to physical weight was proved only with Carbadox at a dose of 2 mg kg-1 and Nitrovin (only in males) in doses of 10 and 50 mg kg-1 p . o . An overdosing of Carbadox revealed rather a negative effect, because already a dose ten times higher had a negative effect on physical growth and a dose fifty times higher caused obvious toxical symptoms . Glypondin was ineffective in each of the tested doses . The consumption of food per unit of weight increase was reduced after supplying carbadox dosed at 2 mg kg-1 by 25.6% in males and by 10.8% in females . After Nitrovin the intake of food was reduced most after a dose of 10 mg kg-1 in both sexes (8.6 and 8.4% respectively) . The most frequent effect on the change of physical weight was the relative reduction in weight of the thyroid gland . For the screening of stimulators laboratory rats are not very suitable.

Antibiotiki, 1977 Jun, 22(6), 498 - 502
{Anthracycline antibiotic, beromycin . The formation of complexes with DNA and the suppresion of nucleic acid biosynthesis}; Ostanina LN et al.; Beromycin, an antitumor anthracycline antibiotic formed in vitro complexes with native and denaturated DNA and ribosomal RNA . Beromycin had a comparatively low constant of DNA binding and to a less extent increased the melting temperature and viscosity of DNA than the other anthracycline antibiotics . A peculiar property of beromycin was very slow binding with DNA, the complex formation was completed in 60 minutes . Beromycin had a selective inhibitory effect on synthesis of nucleic acids in bacterial and tumor cells . Beromycin inhibited synthesis of RNA in the DNA-dependent RNA-polymerase reaction when both the native and denaturated DNA were used as the template . A lower biological activity of beromycin as compared to the other anthracycline antibiotics, such as rubomycin or carminomycin may be explained by lower affinity of this antibiotic to DNA.

Br J Surg, 1977 Jun, 64(6), 394 - 6
A prospective trial of prophylactic antibiotics in hand lacerations; Roberts AH et al.; A series of 368 patients with hand lacerations which required suturing were randomly allocated to one of three treatment groups . The incidence of infected and of imperfectly healed wounds was noted 7 days after suturing . As well as the influence of antibiotics on healing, sixteen other factors which it was considered might affect healing were analysed . The overall infection rate was 9-8 per cent, and there was no significant difference between the three groups . The imperfect healing rate (which includes the infected cases) was 24-6 per cent . There was a lower rate (P less than 0-05) of imperfect healing in the Triplopen group (15 per cent) than in either the flucloxacillin group (29-5 per cent) or the group who received no antibiotics (29-0 per cent) . Other factors associated with imperfect healing found to be significant at the 1 per cent level, were wound contamination, pain and the presence of a wet or changed dressing at the second examination.

Ann Surg, 1977 Jun, 185(6), 634 - 41
Intraoperative antibiotic wound lavage: an attempt to eliminate postoperative infection in arterial and clean general surgical procedures; Lord JW et al.; Intraoperative antibiotic wound lavage has been used in all arterial reconstructive procedures for the past 7 years and reduced the incidence of early and late postoperative infections from 1.5% in 400 operations prior to 1969 to 0.23% (one post-hospital) in 434 patients operated since that date . In 226 consecutive clean major general surgical procedures since June 1971 there has been no early or late wound infections following intraoperative antibiotic wound lavage in contrast to an infection rate of 1.5% in 185 operations prior to that date . A double blind study of 200 patients undergoing operations for varicose veins was carried out as follows: The wounds of alternate patients were irrigated either with normal saline or with antibiotic solution . There were no gross (grade II) postoperative wound infections . Minor skin changes were noted in 93 of 632 incisions in the saline group and only 49 of 608 incisions irrigated with antibiotic solution (P less than 0.001) . In clean operations without antibiotic wound lavage there was a 0.73% rate of in-hospital wound infections in 685 patients in contrast to a zero rate in 760 patients wherein intraoperative wound lavage was carried out throughout the operative procedure.

Surgery, 1977 Jun, 81(6), 692 - 5
The effect of antibiotics on cell-mediated immunity; Munster AM et al.; Normal human lymphocytes in culture were stimulated by the addition of phytohemagglutinin, and deoxyribonucleic acid (DNA) synthesis was measured by the incorporation of tritiated thymidine . The effect of 11 commonly used antibiotics on DNA synthesis then was measured by adding each antibiotic to the culture in concentrations ranging from 2 to 64 microng/ml, a range which covers the plasma levels obtained during customary clinical therapy . Severe dose-dependent suppression of DNA synthesis was found in the presence of two preparations of minocycline, oxytetracycline, and the ascorbic acid salt of tetracycline . Less severe but stil significant suppression was found in the presence of chloramphenicol, clindamycin, tetracycline, and ascorbic acid alone . No effect was noted when penicillin, carbenicillin, or cephalothin was added, and slight stimulation was found in the presence of gentamicin . It is postulated that these findings may help to explain fungal and viral superinfection following antibiotic therapy and that they may play a role in the failure of antibiotic therapy to eliminate some infections.

J Thorac Cardiovasc Surg, 1977 Jun, 73(6), 944 - 7
Postoperative chest wound infections in patients requiring coronary bypass . A controlled study evaluating prophylactic antibiotics; Sutherland RD et al.; A controlled study investigating clean chest wound infections in 904 patients undergoing myocardial revascularization was performed . Four hundred fifty-one patients received systemic antibiotics before and after the operation, and 453 patients received no prophylactic systemic antibiotics . The infection rate was 1.10 per cent and 1.76 per cent, respectively, indicating no statistical difference between the two groups . Preoperative skin preparation and subsequent local antibiotic wound irrigation may be the most important factors in preventing clean wound infection.

J Dairy Sci, 1977 Jun, 60(6), 954 - 60
Antibiotics for elimination of mycoplasmas and ureaplasma from bovine semen; Truscott RB et al.; Minocin at 500 micrograms/ml of semen extender eliminated ureaplasma from naturally or artificially infected bovine semen . Minocin with lincospectin eliminated Acholeplasma laidlawii, Mycoplasma bovigenitalium, bovis, canadense, and arginini from artificially infected semen . Stabilization times of 15 min at 35 C and 3 h at 4 C are important considerations to maximize antibiotic activity.

Postgrad Med, 1977 Jun, 61(6), 92 - 8
Treatment of acne with topical antibiotics; Frank SB; The introduction of topical antibiotics for acne vulgaris has ushered in a new era in the treatment of this troublesome disorder . Tetracycline, erythromycin, and clindamycin can now be prepared in lotion form in vehicles that are capable of carrying the antibiotic into the follicular canal, where the primary lesion of acne occurs . Topical antibiotics are practically as effective as oral antibiotics in treating acne and are particularly useful for mild papular acne of puberty and early adolescence and papular-pustular acne of adult women . Use of topical antibiotics avoids the possibility of the adverse effects of systemic therapy; the side effects from the formulations reported here are negligible . Above all, antibiotic lotions do not produce the dryness and scaling that occur with most other topical acne preparations.

Can J Biochem, 1977 Jun, 55(6), 630 - 5
Studies related to antitumor antibiotics . Part IX . Reactions of carzinophillin with DNA assayed by ethidium fluorescence; Lown JW et al.; The reactions of the antitumor antibiotic carzinophillin (CZ) with native DNAs and synthetic polynucleotides have been examined by an ethidium fluorescence assay . CZ rapidly produces covalent linkage of the complementary strands of a variety of DNAs without activation . This process is accompanied by extensive alkylation, as detected by reduced fluorescence due to destruction of potential intercalation sites for ethidium . These processes which occur without loss of purine or pyrimidine bases show a preference for bonding to guanine groups (but not at the N-7 position) . Examination of the reversibility of the cross-links suggests they involve one 'permanent' link to guanine and a second weaker linkage, possibly to a cytosine residue . Both cross-linking and alkylation show strong pH dependence and are favored at lower pH, suggesting that reactive sites on the antibiotic are basic . The addition of intercalating agents to DNA before treatment with CZ inhibits the cross-linking.

Arch Microbiol, 1977 May 13, 113(1-2), 121 - 30
Ophiocordin, an antifungal antibiotic of Cordyceps ophioglossoides; Kneifel H et al.; An unknown antibiotic, ophiocordin, C21H22N2O8, MW: 430, was isolated from submerged cultures of Cordyceps ophioglossoides, strain TU 276, grown in a glycerol soybean meal medium at 27 degrees C . The antibiotic was extracted from acidified culture fluids with n-butanol and purified by subsequent column chromatography on DEAE-Sephadex and cellulose . Studies including nuclear magnetic resonance and mass spectrometry resulted in proposals of partial structures of the molecule . Inhibition by ophiocordin could be demonstrated for a small number of fungi belonging to different taxonomic groups . Bacteria were not inhibited . The antifungal effect was antagonized by ammonia and nitrate ions and by certain amino acids.

Ann Ophthalmol, 1977 May, 9(5), 615 - 8
Toxicity of selected antibiotics in vitreous replacement fluid; Stainer GA et al.; Experiments with rabbits demonstrated no toxic effects on the retina after vitrectomy when the infusion fluid contained either 20 microgram/ml chloramphenicol saline, 10 microgram/ml amikacin saline, 10 microgram/ml tobramycin saline, or 10 microgram/ml clindamycin saline . We found abnormal electroretinograms and abnormal histologic findings in eyes receiving vitreous replacement with these same drugs in higher concentrations.

An Esp Pediatr, 1977 May, 10(5), 473 - 82
{Acute gastroenteritis . Clinical evolution without use of antibiotics (author's transl)}; Vitoria Cormenzana JC et al.; Authors present a prospective study upon 193 cases of acute gastroenteritis in infants 1 to 24 months of age, giving special attention to clinical evolution of the disease without any use of therapy of either antibiotics or other antidiarrheal agents . Data on epidemiology and etiology of this series are similar to those previously reported by other authors . Mean duration of diarrhea was 2,5 days, whereas mean hospital stay was 7,5 days . The number of cases of prolonged diarrhea was 13, from which six were cases of lactose intolerance, six were cases of cow's milk protein intolerance and one was a case of intractable diarrhea . The little use fulness of antibiotics in the treatment of acute diarrhea is commented and also a discussion is made of the different factors involved in the onset of the complications above mentioned.

Antibiotiki, 1977 May, 22(5), 400 - 4
{Lipid makeup of the initial and selected strains of Actinomyces levoris and Streptoverticillium mycoheptinicum in the process of antibiotic synthesis}; Efimova TP et al.; The study of the lipid composition showed that the rate of the changes in the fatty acid composition of neutral lipids and phospholipids in the selected strains was higher than that in the initial strains . The medium composition had the decisive effect on the fractional and fatty acid spectrum of the mycelium lipids . When the antibiotic-producing organisms were grown on the synthetic medium the phospholipids were the predominating fractions (70--90 per cent of the total lipids), while with the use of organic medium they amounted only to 30--40 per cent . The data were evident of complex correlation between the synthesis of fatty acids and polyenic antibiotics, i.e . levorin and mycoheptin.

J Bone Joint Surg Br, 1977 May, 59(2), 200 - 5
Antibiotic-loaded acrylic cement; Elson RA et al.; Laboratory experiments and clinical investigations have confirmed the various claims made originally by Buchholz and Engelbrecht (1970) that antibiotic-loaded acrylic cement releases the antibiotic into the surroundings in useful concentrations . Palacos R cement released higher concentrations than CMW, Simplex and Sulfix brands of cement and over longer periods . Concentrations of gentamycin and fucidin were sufficient to penetrate dead cortical bone . These conclusions need to be assessed with animal studies, mechanical testing and clinical results before the ideal place of antibiotic-loaded acrylic cement is established.

Can J Microbiol, 1977 May, 23(5), 626 - 9
Effects of temperature and antibiotics on appressorium formation in spores of Colletotrichum lagenarium; Tani M et al.; Effects of temperature (32 degrees C), cycloheximide, and blasticidin-S on spore germination and appressorium formation of Colletotrichum lagenarium were investigated . Temperature treatment at 32 degrees C, given just before the emergence of the germ tube 4 h after incubation at 24 degrees C, significantly inhibited appressorium formation . Cycloheximide (1 ppm) or blasticidin-S (7 ppm) appeared to have reversed the effect of 32 degrees C treatment by producing appressoria in 30% of the germinated spores.

Circ Res, 1977 May, 40(5), 489 - 97
Effects of the antibiotic ionophore X-537A on contractility and ionic exchange in rabbit ventricular myocardium; Wendt IR et al.; The effects of the ionophore X-537A on mechanical function and on ionic exchange were studied in the isolated, arterially perfused rabbit interventricular septum . X-537A produced an initial positive inotropic response which was, however, transient in this preparation and appeared to be dependent on an effect of the ionophore on catecholamines . The positive inotropy gave way to a progressive decline in force development which was unrelated to the action of catecholamines and was not accompanied by the development of contracture . Isotope uptake experiments revealed that coincident with this decline in force development there was a continuous net loss of tissue K+ and a net gain of Na+ . X-537A (5 micronM) perfused for 20 minutes resulted in a net K+ loss of 50.2 +/- 4.6 mmol/kg dry weight and a net Na+ gain of 74.0 +/- 4.5 mmol/kg dry weight . Isotope washout experiments confirmed that the entire net loss of K+ could be accounted for by increased K+ efflux . X-537A did not alter Na+ efflux nor did it have any detectable effect on 45Ca exchange of the perfused septum in which the ability to detect net movements is at a level of approximately +/- 550 micron mol/kg dry weight . On removal of the ionophore the decline in force development ceased and reversed to near control levels and the progressive ionic changes ceased . However, despite the near total recovery of contractile function the Na+ and K+ levels remained at values little different from those reached at the termination of X-537A perfusion . In addition, after removal of the ionophore, we found that K+ exchange rate remained significantly less than control and, furthermore, a kinetic inhomogeneity of tissue K+ was observed . The results emphasize a dissociation between cellular Na+ and K+ content and function following the ionic perturbations induced by the ionophore.

Anesth Analg, 1977 May-Jun, 56(3), 373 - 7
Neuromuscular block by antibiotics: polymyxin B; Lee C et al.; Characteristics of neuromuscular block produced by polymyxin B (PXB) were examined in 12 anesthetized cats, using sciatic nervetibialis anticus muscle preparations . The ED50 was 6.7 (+/- 1.4, SD) PXB base/kg body weight . The ED95 was 10.8 (+/- 2.4) mg/kg . Spontaneous recovery from 25 percent of control to 75 percent of control required 72 (+/- 16) minutes . During a 50 percent block, train-of-four twitches elicited at 2 Hz faded with a train-of-four ratio of 0.42 (+/- 0.13), but the tetanus did not fade . Edrophonium Cl, neostigmine methylsulfate, and pyridostigmine Br at sub-clinical dosages weakly antagonized the block but enhanced the block at anti-curare dosages . All 3 cholinesterase inhibitors were short acting, lasting 10 to 15 minutes, and noncumulative on repeated injection . The potency ratio was approximately 20:10:1 in the order of edrophonium, neostigmine, and pyridostigmine on a weight-for-weight basis . Calcium partially antagonized the block . The authors conclude that neuromuscular blocks produced by various antibiotics differ from each other and from that produced by other groups of neuromuscular blocking agents, including curare.

Antibiotiki, 1977 May, 22(5), 460 - 5
{Effect of coamide on immunogenesis during antibiotic therapy}; Nikolaev AI et al.; The dynamics of the antibody-producing cells in the spleen and the titer of hemagglutinines in the blood of albino mice immunized with sheep erythrocytes and treated with various doses (250, 500, 1000 gamma) of oxytetracycline and monomycin and their combinations with coamide, a complex of cobalt with nicotinic acid amide at different periods after the immunization . It was found that oxytetracycline in doses of 500 and 1000 gamma and monomycin in doses of 250, 500 and 1000 gamma administered intramuscularly for 4 days had an inhibitory effect on both the antibody-producing cells and the titer of hemagglutinines in the immunized animals at various periods after the immunization . Consequently, oxytetracycline and monomycin had the immunosuppressive effect . Exposure of the animals treated with oxytetracycline and monomycin to coamide for 5 days provided an increase in the number of the antibody-producing cells and the titer of the hemagglutinines . The results of the study showed the perspectivity of coamide use in complex therapy of infectious diseases.

Laryngol Rhinol Otol (Stuttg), 1977 May, 56(5), 432 - 6
{Improved differentiation of suspected chronic laryngeal lesions by highly dosed antibiotic therapy for a short time and comparing cytology (author's transl)}; Franz B et al.; The valuation of chronic laryngeal lesions is eased by a combination of a highly dosed antibiotic therapy for a short time and observation of the therapy procedure by cytology . The cytological estimated dyscaryoseindex gives reference if suspicion on a malignant lesion can be kept in mind . Above this the proceeding enables us for exact and useful biopsies respectively for primary diagnostic and therapeutic operations.

Laryngol Rhinol Otol (Stuttg), 1977 May, 56(5), 409 - 14
{The intratympanic treatment of Menière's disease with ototoxic antibiotics . A follow-up study of 55 cases (author's transl)}; Lange G; Report about 55 patients suffering from severe unilateral Menieres disease, seen over a period of 3-10 years . They were treated with intratympanic administration of Streptomycinesulfate or- better -Gentamycinesulfate . The medication was given using a plastic tube inserted behind the annulus by transmeatal approach . 0.1 ml Gentamycinesulfate (earlier Streptomycinesulfate were instillated every 5 hours until the first signs of inner-ear-reaction (nystagmus or vertigo) appeared . -In 90% of the cases vertiginous attacks ceased after therapy . Hearing was preserved in 76%, tinnitus and periaural pressure were influenced markedly.

Eur J Biochem, 1977 Apr 15, 74(3), 539 - 47
Cooperative and antagonistic interactions of peptidyl-tRNA and antibiotics with bacterial ribosomes; Contreras A et al.; There is a single-site interaction of {methylene-14C}thiamphenicol and {methylene-14C}chloramphenicol with run-off ribosomes with dissociation constants Kd = 6.8 micronM and Kd = 4.6 micronM respectively . Similar affinities for the antibiotics are observed in polysomes totally deprived of nascent peptides, or bearing nascent peptides on the A-site . However, two types of interaction are observed in endogenous polysomes with some ribosomes bearing nascent peptides on the P-site and other in the A-site . The lower-affinity bindings (dissociation constants Kd = 6.4 micronM and Kd = 1.5 micronM for thiamphenicol and chloramphenicol respectively) are due to the ribosomes bearing nascent peptides on the A-site . The higher-affinity bindings (dissociation constants Kd = 2.3 micronM and Kd = 1.5 micronM for thiamphenicol and chloramphenicol, respectively) are due to the ribosomes bearing nascent peptides on the P-site . Therefore binding of nascent peptides to the A-site does not affect the affinities of thiamphenicol and chloramphenicol for the ribosome . On the other hand interaction of the nascent peptides with the P-site of the ribosomes increases the affinities of both antibiotics for the ribosome . Thiamphenicol and chloramphenicol are thus good inhibitors of peptide bond formation in ribosomes and polysomes . Their affinities are increased precisely when the peptidyl-tRNA is placed in the P-site preceeding the peptide bond formation step, which is specifically blocked by the antibiotics . There is a single-site interaction per ribosome for {35S}thiostrepton, which does not appear to be affected by the attachment to the ribosomes of mRNA, tRNA and nascent peptides either to the A or the P-site . {N-methyl-14C}Lincomycin, {N-methyl-14C}erythromycin, {G-3H}streptogramin B and {G-3H}-streptogramin A bind to run-off ribosomes and polysomes totally free from nascent peptides . However, these antibiotics do not interact with ribosomes bearing nascent peptides either in the A or the P-site and therefore are not active on preformed polysomes . Thus lincomycin and streptogramin A only interact with free ribosomes and 50-S subunits and block the early rounds of peptide bond formation prior to polysome formation . Erythromycin and streptogramin B do not inhibit either initiation or the first round of peptide bond formation . However, erythromycin and streptogramin B, prebound to the ribosome, block peptide elongation probably by steric hindrance with the growing oligopeptide chain when this reaches a certain critical length.

Biochim Biophys Acta, 1977 Apr 11, 460(1), 157 - 62
Funiculosin: an antibiotic with antimycin-like inhibitory properties; Nelson BD et al.; The antibiotic funiculosin mimics the action of antimycin in several ways . It inhibits the oxidation of NADH and succinate, but not TMPD+ascorbate . The titer for maximal inhibition in Mg2+-ATP particles (0.4-0.6 nmol/mg protein) is close to the concentrations of cytochromes b and cc1 . Funiculosin also induces the oxidation of cytochromes cc1 and an extra reduction of cytochrome b in the aerobic steady state, and it inhibits duroquinol-cytochrome c reductase activity in isolated Complex III . The location of the funiculosin binding site is clearly similar to that of antimycin . In addition, funiculosin, like antimycin, prevents electron transport from duroquinol to cytochrome b in isolated Complex III if the complex is pre-reduced with ascorbate . Funiculosin and antimycin differ, however, in the manner in which they modulate the reduction of cytochrome b by ascorbate+TMPD.

Biochim Biophys Acta, 1977 Apr 4, 475(3), 521 - 35
Pyrrolo(1,4)benzodiazepine antitumor antibiotics . In vitro interaction of anthramycin, sibiromycin and tomaymycin with DNA using specifically radiolabelled molecules; Hurley LH et al.; Anthramycin, tomaymycin and sibiromycin are pyrrolo(1,4)benzodiazepine antitumor antibiotics . These compounds react with DNA and other guanine-containing polydeoxynucleotides to form covalently bound antibiotic - polydeoxynucleotide complexes . Experiments utilizing radiolabelled antibiotics have led to the following conclusions: 1 . Sibiromycin reacts much faster than either anthramycin or tomaymycin with DNA . 2 . At saturation binding the final antibiotic to base ratios for sibiromycin, anthramycin and tomaymycin are 1 : 8.8,1: 12.9, and 1 : 18.2, respectively . 3 . No reaction with RNA or protein occurs with the pyrrolo(1,4)benzodiazepine antibiotics . 4 . Sibiromycin effectively competes for the same DNA binding sites as anthramycin and tomaymycin; however, there is only partial overlap for the same binding sites between anthramycin and tomaymycin . 5 . Whereas all three pyrrolo(1,4)benzodiazepine antibiotic-DNA complexes are relatively stable to alkaline conditions, their stability under acidic conditions increases in the order tomaymycin, anthramycin and sibiromycin . 6 . No loss of non-exchangeable hydrogens in either the pyrrol ring or the side chains of these antibiotics occurs upon formation of their complexes with DNA . 7 . Unchanged antibiotic has been demonstrated to be released upon acid treatment of the anthramycin-DNA and tomaymycin-DNA complexes . 8 . A Schiff base linkage between the antibiotics and DNA has been eliminated . The comparative reactivity of the three antibiotics towards DNA and the stability of their DNA complexes is discussed in relation to their structures . A working hypothesis for the formation of the antibiotic-DNA covalent complexes is proposed based upon the available information.

Gann, 1977 Apr, 68(2), 213 - 9
Antitumor activity of a new antitumor antibiotic, sporamycin; Komiyama K et al.; Sporamycin is an antitumor antibiotic isolated from the culture filtrate of Streptosporangium strain No . PO-357 . Hydrolysate of the antibiotic showed at least 12 kinds of amino acid, and the molecular weight was calculated approximately as 8,500 approximately 9,000 . Antitumor activities of Sporamycin were examined on murine tumors according to different schedules of treatment . After nine daily doses of the antibiotic had been given to dd mice bearing Ehrlich ascites carcinoma, significant increase of lifespan was observed at doses of 5.0 approximately 1.3 mg/kg . A marked decrease in tumor size of sarcoma-180 transplanted subcutaneously was observed when the mice were treated by daily or single injection of Sporamycin . Against leukemia P-388 and L-1210 inoculated intraperitoneally into CDF1 mice, the antibiotic increased lifespan of leukemic mice . The antibiotic also inhibited significantly the growth of human tumor cells in vitro.

Antibiotiki, 1977 Apr, 22(4), 361 - 5
{Cytotoxic and antitumor effect of antibiotic PSX-1 in vitro and in vivo}; Fuchs J; The inhibitory effect of antibiotic PSX-1 on tumour cells was studied in vitro and in vivo . The antibiotic inhibited above all the utilization of the added 14C-labelled uridine and adenine in EAC cells . After a short exposure to PSX-1 (180 min) the synthesis of nucleic acids and proteins in EAC proliferating in vitro was suppressed . Antibiotic PSX-1 in concentrations of about 2.5 mg/ml showed relatively low toxicity on normal human fibroblasts but caused a marked cytotoxic and cytopathic effect on tumour cells . A potential antitumor effect of PSX-1 was evaluated in vivo by using gradually EAC and L 1210 tumours . All the animals treated with the antibiotic in doses of 2.5--5.0 mg/kg/day with the use of EAC and 5.0 mg/kg/day with the use of L 1210 survived for 90 and 40 days respectively and no tumours developed in the treated mice during this period.

J Biochem (Tokyo), 1977 Apr, 81(4), 1127 - 32
Inhibition of the biosynthesis of leucomycin, a macrolide antibiotic, by cerulenin; Takeshima H et al.; Cerulenin, an inhibitor of fatty acid synthesis, specifically inhibits the biosynthesis of leucomycin, a 16-membered macrolide antibiotic, in both growing cells and resting cells of Streptomyces kitasatoensis . In growing cells, the production of leucomycin was inhibited as long as cerulenin remained in the culture . In resting cells, 50 percent inhibition was achieved with a cerulenin concentration of 1.5 microgram/ml . Cells in which leucomycin synthesis was inhibited for 9 h remained capable of leucomycin synthesis upon removal of the inhibitor . Cerulenin specifically inhibits the incorporation of {14C}acetate into leucomycin but does not affect total protein or RNA synthesis . The uptake of {14C}acetate was not inhibited under conditions which completely inhibited the incorporation of acetate into leucomycin . Since cerulenin is known to block the condensation of malonyl-CoA subunits in the formation of fatty acids, it can be concluded that the aglycone of leucomycin is synthesized via the polyketide pathway by condensation steps similar to those involved in fatty acid biosynthesis.

J Antibiot (Tokyo), 1977 Apr, 30(4), 321 - 5
Effect of polyene macrolide antibiotics on invertebrate tissue culture cells; Goldstein NI et al.; The effect of amphotericin B (AB) and amphotericin B methyl ester (AME) on viability and DNA synthesis in three insect cell lines, Trichoplusia ni (Tn) Carpocapsa pomonella 169 (Cp) and Aedes aegypti (Aa), has been evaluated . In all cases AME was less toxic than AB and inhibited DNA synthesis to a lesser degree than AB . However, the three cell lines differed in their response to the two polyene macrolide antibiotic preparations . Tn and Aa cell responded in a similar manner when exposed to either AME or AB, whereas Cp cells were more sensitive to both antibiotics than Tn or Aa cells.

Antibiotiki, 1977 Apr, 22(4), 357 - 61
{Study of the toxicity and antiblastoma activity of antibiotics echinomycin and 6270 in complexes with DNA}; Bazhanov VS et al.; Studies with the use of intact inbred albino mice showed that in intravenous administration the acute toxicity of antibiotic No . 6270 and echinomycin in complexes with DNA increased 3--4 times as compared to the toxicity of the same antibiotics used without the complex . Under the experimental conditions with 3-fold intravenous administration at 72-hour intervals in doses equivalent by their acute toxicity, the antitumor activity of the echinomycin complex with DNA against the solid form of lymphosarcoma L10-1 was approximately 4 times lower than the activity of the antibiotic used alone . Like echinomycin, antibiotic No . 6270 in complex with DNA used according to the same administration scheme in doses equivalent by their acute toxicity had a lower inhibitory effect on growth of lymphosarcoma L10-1 and sarcoma 180 as compared to its use alone.

Biokhimiia, 1977 Apr, 42(4), 653 - 8
{Effect of metalloproteins on the photochemical activity of chloroplasts treated with polyene antibiotics}; Mutuskin AA et al.; The effects of various metall-containing proteins (plastocyanin, plantacyanin, azurine and cytochromes of the f type) on the activity of photosystem I of chloroplasts, treated with polyene antibiotics, were studied . The inhibiting effect of the polyenes, surgumycin and philipin, was completely removed by an addition of copper-containing protein plastocyanin . No similar effect was exerted by other Cu-containing proteins--azurine and plantacyanin . The cytochromes of the f type isolated from the green algae chlorella, blue-green algae spiruline and aphanezomenone, having different electrophoretic properties, restored the activity of photosystem I of chloroplasts incubated with antibiotics in a different degree . Acid cytochrome f of chlorella restored the activity by 80--100%; less acid cytochrome f from spiruline-only by 50% . The least restoring effect was exerted by aphanezomenone cytochrome, which possesses some basic properties . The chloroplasts treatment with surgumycin did not affect the isolation of the terminal enzyme of the chloroplast electron-transporting chain of ferredoxin--NADP--reductase . Possible environment of plastocyanin in the chloroplast membrane and the mechanism of photosystem I restoration are discussed.

Surg Gynecol Obstet, 1977 Apr, 144(4), 507 - 11
Rapid antibiotic disk sensitivities of burn eschar and infected wounds; Verklin R et al.; This study was undertaken to develop a more rapid antibiotic sensitivity test of the pathogens in soft tissue infections and burn wound eschar . The proposed rapid antibiotic sensitivity test was performed directly on the clinical specimen rather than on single strains of bacteria isolated from the tissue . By performing the antibiotic sensitivity tests directly on the tissue sample, the physician obtains the test results within seven hours after receiving the specimen rather than 38 to 52 hours later, the time delay encountered with the conventional technique . The modification used did not alter most of the standards advised by the Food and Drug Administration (3), since there was no inclusive change in medium, agar depth or antibiotic sensitivity disk . The changes in the Kirby-Bauer (1) test necessitated by using the clinical specimen did not alter significantly the interpretation of the antibiotic susceptibility . If clinically significant numbers of bacteria, 10(6)-10(9), were present, variations in the inoculum size did not appreciably change the results of the antibiotic susceptibility tests . If the incubation requirement for the standard Kirby-Bauer (1) antibiotic susceptibility test was reduced to seven hours, it also did not significantly limit the accuracy of the test . As expected, the variable most difficult to standardize was the heterogeneous inoculum containing large numbers, 10(7), of different organisms . A zone of inhibition interpreted as sensitive with one organism was occasionally masked by the presence of the confluent growth of an organism in which the zone of inhibition was considered resistant . However, even in this instance, it is possible that mixed culture sensitivities may provide the most valid information in mixed infections, since they more closely simulate the real clinical situation.

Acta Physiol Scand, 1977 Apr, 99(4), 399 - 411
Effect of the polyene antibiotic filipin on the permeability of the inward- and the outward-facing membranes of the isolated from skin (Rana temporaria); Nielsen R; The effect of the polyene antibiotic filipin on the electrical properties and the passive permeability of the cell membranes was investigated . The addition of filipin to the outside bathing solution has the following effects: 1 . it results in a drastic reduction in the transepithelial resistance and potential, 2 . it causes a 10-20 times increase in the passive transepithelial chloride, sodium and sucrose flux, 3 . it results in the formation of an amiloride insensitive sodium pathway in the outward facing membrane, 4 . it results in an active outward transport of potassium, 5 . it results in a highly significant swelling of all the cells in the epithelium . The addition of filipin to the inside bathing solution has the following effects 1 . it results in an activation of the active sodium transport, 2 . it causes a slight increase in the passive transepithelial chloride and sodium permeabilities but has no effect on the sucrose permeability, 3 . it has no effect on the amiloride inhibition of the short-circuit current, 4 . it has no effect on the volume of the cells in the epithelium . It is suggested that the addition of filipin to the outside bathing solution increases the direct sodium flow from cell to cell in neighbour layers . Furthermore these experiments indicate that the outward facing membrane of the isolated frog skin has a high cholesterol content as compared with the cholesterol content of the inward facing membrane.

Arch Ophthalmol, 1977 Apr, 95(4), 682 - 5
Drug interaction in the eye . Concurrent corticosteroid-antibiotic therapy for inflammatory keratitis; Leibowitz HM et al.; Concurrent instillation of individual preparations of a corticosteroid and an antibiotic resulted in significantly (P less than .05) lower peak corneal and aqueous humor steroid levels than those achieved by the steroid alone . Both the interval elapsing between instillation of the two drugs and the sequence in which they were administered influenced subsequent steroid bioavailability . Corticosteroid levels in the cornea after administration of a combination steroid-antibiotic preparation were not significantly different (P less than .05) from those detected after instillation of the same steroid alone, suggesting that, for the treatment of corneal disorders, use of a combination preparation may offer a method to circumvent certain drug interactions . The decrease in ocular steroid bioavailability could not be directly equated with differences in antinflammatory effectiveness, so that the therapeutic relevance of the demonstrated drug interaction is not known.

Biochim Biophys Acta, 1977 Mar 29, 497(1), 253 - 9
The effect of antibiotics on the electrical polarisability of aqueous suspensions of bacteria; Morris VJ et al.; The orientation of washed Escherichia coli bacteria in suspension induced by applied a.c . electric fields has been monitored by observing the accompanying changes in the intensity of light scattered by the suspension . The data enable the anisotropy of electrical polarisability deltaalpha to be determined . Changes in deltaalpha due to the addition of various antibiotics to the suspension have been measured as a function of both the antibiotic concentration and the temperature of the suspension . The results are taken to indicate that there is an accumulation of the antibiotic molecules at the bacterial surface.

Minerva Med, 1977 Mar 24, 68(14), 917 - 28
{Pharmacokinetic and clinical research on a new antibiotic combination (amoxicillin and flucloxacillin in equivalent-weight dose)}; Di Nola F et al.; A controlled double-blind biometric and an open clinical trial were conducted to determine the therapeutic effectiveness of a new equal-dose w/w association of amoxicillin and flucloxacillin . The following conclusions were drawn . Both antibiotics were present in high serum levels; those of flucloxacillin were higher and more persistent . Analysis of variance on 89 patients pointed to the superiority of the association by comparison with amoxicillin alone . The clinical study made it clear that the broad and complementary spectrum of the association, its synergy, absence of toxicity and good gastric tolerance make it a valuable and effective therapeutic aid, also in presence of germs that produce beta-lactase.

J Chromatogr, 1977 Mar 21, 133(2), 291 - 301
Thin-layer chromatographic classification of antibiotics exhibiting antitumor properties; Issaq HJ et al.; A classification system for 151 antibiotics exhibiting antitumor properties using thin layer chromatography (TLC) and bioautography was developed . TLC classification is based on mobility of the compounds in a solvent system using a certain adsorbent, rather than on misleading RF values . The solvent systems and conditions used are presented.

Nouv Presse Med, 1977 Mar 19, 6(11), 923 - 6
{Nephrotoxicity of gentamicin . Conditions for the use of this antibiotic in the elderly and in the patient with renal insufficiency}; Jungers P et al.; Reversible acute renal failure was observed in 13 patients after combined antibiotic therapy using gentamicin . High and prolonged doses were used in 7 patients whose initial renal function was normal, while 6 other patients with preceding chronic renal insufficiency received usual doses of gentamicin . Precipitating factors were: increasing age, previous renal impairment, and combined use of other antibiotics, mainly cefalotin (8 patients) . The nephrotoxicity of gentamicin is poor but well established, and may be prevented by checking the initial renal function, adjusting the dosage subsequently, and monitoring the renal function and gentamicin serum levels during therapy.

Experientia, 1977 Mar 15, 33(3), 306 - 8
Chdromosome aberrations in mice by the antifungal antibiotic, nystatin; Manna GK et al.; Nystatin, a fungicide of current medical use, was tested in mice for its effect on chromosomes of bone marrow cells . A significant increase of aberrations, mostly of chromatid type, was observed over a period of from 15 min to 15 days following the application of the drug . Our data indicate a non-random distribution of the breaks.

Biochem J, 1977 Mar 15, 162(3), 681 - 7
Studies on the cell-free biosynthesis of beta-lactam antibiotics; Bost PE et al.; Cell walls of Cephalosporium acremonium mycelia were lysed by enzyme preparations from either Helix pomatia (snail) digestive juice or Cytophaga . The yield of protoplasts depended on the lytic-enzyme preparation and the age of the culture, and it increased after the mycelia were pretreated with dithiothreitol . A cell-free preparation, obtained by osmotic lysis of protoplasts, synthesized labelled penicillin N from L-{14C}valine . Approx . 0.03-0.06% of the amino acid was incorporated into penicillin N . Under conditions of penicillin N synthesis, the broken-protoplast preparation failed to produce significant amounts of cephalosporin C or its precursors, deacetylcephalosporin C and deacetoxycephalosporin C.

Experientia, 1977 Mar 15, 33(3), 327 - 8
{Influence of nystatine, a polyene antibiotic, on the formation of complex-bound sterols and the formation of conidia by Coprinus cinereus (author's transl)}; Defago G et al.; In contrary to the wild strain, a monocaryotic mutant of Coprinus cinereus (basidiomycete) does not contain hydrosoluble, complex-bound sterols . Under nystatine-treatment, however, the mutant is induced to produce this kind of stereols in abundance . Furthermore, nystatine highly increases sporulation of the mutant and decreases sporulation of the wild strain.

Ann N Y Acad Sci, 1977 Mar 4, 284, 544 - 65
Interruption of oncornavirus replication by modified rifamycin antibiotics; O'Connor TE; Thirteen rifamycin SV derivatives containing 3'-alkylaminomethyl substituents fail to inhibit the activities of the simian sarcoma virus Type 1 DNA polymerase, and of cellular DNA, RNA, and poly(A) polymerases prepared from NIH Swiss mouse embryos . These compounds show a range in their toxicities for NIH Swiss mouse 3T3 cells and in their capacities to inhibit production of foci of morphologically altered cells by murine sarcoma virus (MSV) . Three compounds--the N-methyl-N-hydroxyethylaminomethyl, the N,N-dimethyl-aminomethyl, and the N4-methylpiperazinomethyl rifamycin derivatives--are comparable to adenine arabinoside and ribavirin in their toxicity for 3T3 cells, but these compounds show superior focus inhibition . These compounds inhibit oncornavirus production apparently by exacerbation of a delay in growth that results from infection of 3T3 cells with MSV.

Biochim Biophys Acta, 1977 Mar 2, 475(1), 123 - 30
Peptidyl transferase activity in wheat germ ribosomes . Effect of some antibiotics; Sikorski MM et al.; The formation of N-acetyl-leucyl-puromycin in a "fragment reaction" catalyzed by 80 S ribosomes from wheat germ was characterized . The reaction product was identified by high-voltage electrophoresis . The fragment reaction is inhibited by sparsomycin, blasticidin S, gougerotin and to a lesser degree by amicetin and tetracycline . Formation of an acLeu-pentanucleotide-ribosomes complex was strongly stimulated by sparsomycin.

Tsitologiia, 1977 Mar, 19(3), 361 - 6
{Effect of the ionophore antibiotic valinomycin on the lymphocyte blast-transformation reaction induced by phytohemagglutinin}; Astashkin EI et al.; The effect of valinomycin on blast-transformation of human lymphocytes has been studied . The lymphocyte response was assayed by incorporation of radioactive precursor into DNA . DNA synthesis by PHA-stimulated lymphocytes was inhibited by valinomycin at concentration of 10(-8) M . The effect of high concentrations of valinomycin on the cells appeared to be irreversible . Excess of potassium in the medium was not effective in preventing the inhibitory action of valinomycin . An extensive washing of cells did not result in any release of the bound drug in the 10(-8) M concentration . The results are consistent with a hypothesis that lymphocyte stimulation is critically dependent on the level of intracellular K+.

J Antibiot (Tokyo), 1977 Mar, 30(3), 239 - 43
Studies on the ionophorous antibiotics . VIII . Effects of monovalent and divalent cation ionophores on blood platelets; Mitani M et al.; The effects of a monovalent cation ionophore etheromycin (CP-38295) and a divalent cation ionophore lysocellin on blood platelets function have been investigated . When platelets were incubated with 3 micronM of each ionophore, the simultaneous induction of secretion of stored serotonin and efflux of intracellular calcium occurred, but there was no detectable influx of extracellular calcium . With increasing concentrations, these compounds caused platelet aggregation accompanied by increased influx of external calcium . These results are consistent with the hypothesis that the liberation of calcium from the intracellular store mediated the platelet secretion reaction.

J Antibiot (Tokyo), 1977 Mar, 30(3), 234 - 8
Evaluation of mycobacillin and versicolin as agricultural fungicides . III . Growth pattern and antibiotic production in soil by Aspergillus versicolor; Chattopadhyay JP et al.; Soil supports the growth of a jute pathogen Colletotrichum gloeosporioides but only to a limited extent that of its antagonist Aspergillus versicolor . The growth of the sensitive pathogen is considerably checked by the antagonist in mixed soil culture although versicolin production could not be demonstrated within the limits of assay . Both the sensitive and the antagonistic organisms grow well in soil-compost medium and versicolin production by the latter is also enhanced . The antagonistic effect of Aspergillus versicolor on Colletotrichum gloeosporioides is expectedly more marked in soil-compost medium than in soil medium.

Arch Tierernahr, 1977 Mar, 27(3), 195 - 9
{Effect of the addition of antibiotics on the fattening capacity of broilers fed optimum rations . 4 . Lambdamycin}; Jeroch H et al.; A total of 3426 broilers were used in 3 fattening trials . The birds received supplements of the antibiotic lamdbamycine in amounts of 30 or 40 mg per kg of feed added to adequately balanced fattening rations . OTC supplements (40 mg per kg) which were an obligatory food component at the time of the trial were used as controls . The results obtained may be summarized as follows: Supplements of neither lambdamycine nor oxytetracycline exerted any significant influence on food consumption . Lambdamycine improved the rate of liveweight gains by 2% (trial 1, alpha greater than 0.05) and 5% (trial 2 and 3; trial 2: alpha less than 0.05, trial 3: alpha greater than 0.05) . The growth-promoting effect of OTC was less pronounced than usual (2-3%; alpha less than 0.05) or was completely absent (trial 2) . Lambdamycine decreased the rate of food consumption per unit of weight gain in 2 trials (trial 2: alpha less than 0.01) OTC did not influence the rate of food consumption.

Jpn J Antibiot, 1977 Mar, 30(3), 223 - 7
{Effects of a proteolytic-enzyme preparation used concomitantly with an antibiotic in osteoarticular infections (author's transl)}; Okumura H et al.; Studies were performed in 8 patients with osteoarticular infections to examine the concentrations of sulbenicillin in the venous blood and exudate following administration and the concentrations of the antibiotic in the exudate when serratiopeptidase was orally administered concomitantly with the antibiotic . The results of the examination indicated that the transfer of sulbenicillin into the exudate tended to increase when 30 mg/day of serratiopeptidase was concomitantly given for 6 days, though further examination was thought necessary by increasing number of subjects and elaborating on the methodology.

J Infect Dis, 1977 Mar, 135 Suppl, S58 - 64
Evaluation of clindamycin and other antibiotics in the treatment of anaerobic bacterial infections of the lung; Kapila R et al.; Fifty patients who had pneumonia, lung abscess, or empyema, and whose specimens had a fetid odor, were presumed to be suffering from anerobic lung infection and were treated with clindamycin either orally (33 patients) or parenterally (17) . Forty-six patients showed marked improvement or recovered; two also underwent lung resection, and thoracotomy was performed in 10 . There were three outright treatment failures, and superinfection occurred in one patient . A review of the literature suggests that clindamycin and penicillin (in substantial dosage) are equally effective in treatment of anaerobic lung infection . Transtracheal aspiration is not deemed necessary if the patient is expectorating fetid sputum.

J Med Chem, 1977 Mar, 20(3), 337 - 41
Pyrimidinylpropenamides as antitumor agents . Analogues of the antibiotic sparsomycin; Lin CC et al.; A series of pyrimidinylpropenamides 9 and their oxidation products 10 was prepared, as analogues of sparsomycin (1), for antitumor evaluation . Syntheses involved condensation of the appropriate amino alcohol 5 with acid 8 . The resulting sulfides 9 were then oxidized with NaIO4 or H2O2 to sulfoxides 10 . Activity was studied in lymphocytic leukemia P-338 and KB cell culture . With the exception of the n-decyl analogue, all of the deoxygenated compounds 9 were inactive regardless of the stereochemical form . In the sulfoxide series 10, those compounds prepared with an L configuration at the asymmetric carbon were also inactive . The completely racemic sulfoxides, on the other hand, displayed substantial antitumor activity (ILS = 37-61% in P-388; ED50 = 1.2-2.4 mug/ml in KB) suggesting that both the presence of a sulfoxide moiety and a D configuration at the chiral carbon atom were structural requirements for a positive antitumor response . There appeared to be a large tolerance for the group substituted at the sulfoxide moiety, however.

J Infect Dis, 1977 Mar, 135 Suppl, S126 - 32
Bile acids, diarrhea, and antibiotics: data, speculation, and a unifying hypothesis; Hofmann AF; The primary bile acid, chenodeoxycholic acid, and the secondary bile acid, deoxycholic acid, when present at a concentration of greater than 3 mM, induce salt and water secretion from the human colon and cause a marked increase in the permeability of the human colon to molecules of a molecular weight of 200-500 daltons . Scanning electron microscopy indicates that this action may be associated with tissue damage in some species . In the healthy individual, the primary bile acids, cholic and chenodeoxycholic acid, are dehydroxylated in the colon and are simultaneously precipitated from solution; at pH less than 7, deoxycholic and lithocholic acid are insoluble . In patients with bile acid diarrhea resulting from bile acid malabsorption, dehydroxylation is decreased, and the concentration of bile acids in the colon is markedly elevated . The major secretory bile acid in solution is chenodeoxycholic acid . Administration of cholestyramine, a resin that binds bile acid, reduces the elevated concentration of chenodeoxycholic acid and abolishes the diarrhea . These facts can be used to develop a unifying hypothesis which proposes that elevated concentrations of primary bile acids in the colon play a role in diarrhea and pseudomembranous colitis induced by clindamycin.

Med Klin, 1977 Feb 22, Spec No, suppl 7 - 11
{Retrospective studies of resistance patterns of antibiotics in 1971 to 1974 (author's transl)}; Driessen JH; A retrospective study was made of the resistance patterns of 16700 pathogenic bacterial strains from the region of Dordrecht (Netherlands) from the years 1971 through 1974 . The importance of computer analysis for questions about resistance and antibiotic usage monitoring is supported . The practical importance of those analyses is the fact that antibiotics often have to be given without a known antibiogram . In those instances one must rely on historical data to guide the therapy and to compose a rational antibiotic utilization review . It should be interesting to repeat the study in other areas to establish an overall pattern for a country and to compare the findings on a country-by-country basis.

Med J Aust, 1977 Feb 19, 1(8), 243 - 6
Incidence of antibiotic-related diarrhoea and pseudomembranous colitis: a prospective study of lincomycin, clindamycin and ampicillin; Robertson MB et al.; An existing intensive drug monitoring system was used to study the occurrence of pseudomembranous colitis and diarrhoea in 100 patients treated with lincomycin and clindamycin . In order to give perspective to the results an equal number of matched patients treated with ampicillin were also studied . The incidences of diarrhoea in both groups were similar (11% in the lincomycin-clindamycin group and 8% in the ampicillin group) . One patient developed pseudomembranous colitis associated with two prolonged courses of lincomycin therapy . The results suggest that the risks associated with the use of lincomycin are acceptable if the drug is given for the approved specific indications.

Can Med Assoc J, 1977 Feb 5, 116(3), 256 - 9
Rational and irrational use of antibiotics in a Canadian teaching hospital; Achong MR et al.; Parenteral therapy with gentamicin, cloxacillin, ampicillin and cephalothin was surveyed on a surgical, a gynecologic and medical ward of a teaching hospital . During a 3-month period 219 patients (12.9% of the total number admitted to the three wards) received at least one of the four antibiotics parenterally . Ampicillin and gentamicin were used most frequently on the three wards when the indication for therapy was either infection or empirical use . Cephalothin was used most frequently for prophylaxis in the gynecologic and surgical patients; no medical patient received this drug . Overall, therapy was assessed to be irrational in 42.0, 50.0 and 12.0% of the surgical, gynecologic and medical patients, respectively . Prophylaxis was the indication for therapy in 76.9 and 86.8% of the surgical and gynecologic patients, respectively, for whom the therapy was assessed to be irrational.

Ann Microbiol (Paris), 1977 Feb-Mar, 128(2), 217 - 27
The effect of antibiotics on the infective viability of an alder (Alnus glutinosa L . Gaertn.) crushed nodule inoculum; Costa A et al.; The effect of various antibiotic substances, mainly penicillin, streptomycin, tetracycline and chloramphenicol respectively, on the infective viability of an alder crushed nodule inoculum towards the host plant has been studied . Penicillin was inocuous in respect of both plant and nodule endophyte . Its use did not prevent the formation of nitrogen-fixing partnership . The other antibiotics tested showed a harmful effect either inhibiting infection (streptomycin) or causing death in most plants (tetracycline and chloramphenicol) . The use of penicillin in isolation trials of the alder nodule endophyte is suggested.

Pharmazie, 1977 Feb, 32(2), 101 - 4
The shelf life of some antibiotic preparations stored under tropical conditions; York P; Accelerated storage tests have been carried out to predict the shelf life of several commercial preparations stored directly under temperate and tropical climatic conditions . Two brands each of sulphathiazole tablets, tetracycline hydrochloride capsules and chloramphenicol capsules were studied over a period of three months . Shelf lives ranging from 6.2 . to 29.7 months were predicted for temperate storage conditions (20 degree C/31% R.H.), whilst these periods were reduced giving values from 3.8 to 13.9 months for tropical conditions of 30 degree C/31% R.H and from 2.5 to 9.2 . months when stored at 30 degree C/75% R.H . A decrease in the rate of drug dissolution was also observed for preparations stored directly under conditions of elevated temperature and humidity . The results indicate the need for stringent control over storage conditions for antibiotic preparations in tropical climates to ensure adequate drug stability and dissolution characteristics.

J Antibiot (Tokyo), 1977 Feb, 30(2), 146 - 57
Polyene antibiotics . VIII . The structure of rimocidin; Pandey RC et al.; A structure is assigned to the tetraene antibiotic rimocidin, based in part on 13C NMR spectroscopy and field desorption mass spectrometry . The structure assigned revises a structure proposed in 1966 which was anomalous in relation to those of other polyene antibiotics.

J Antibiot (Tokyo), 1977 Feb, 30(2), 125 - 8
Metabolic products of microoorganisms . 163 . Desferritriacetylfusigen, an antibiotic from Aspergillus deflectus; Anke H; Aspergillus deflectus CBS 109.55 when grown on an iron-free medium produces several antibiotics; one of these was isolated and identified as desferritriacetylfusigen . It inhibits the growth of bacteria, whereas yeasts and fungi are not or only weakly affected.

Can J Physiol Pharmacol, 1977 Feb, 55(1), 48 - 51
Inhibition of the immune response by rapamycin, a new antifungal antibiotic; Martel RR et al.; Rapamycin, a new antifungal antibiotic, was found to inhibit the immune response in rats . It totally prevented the development of two experimental immunopathies (experimental allergic encephalomyelitis (EAE) and adjuvant arthritis (AA)) and the formation of humoral (IgE-like) antibody . It was about half as potent as cyclophosphamide in inhibiting EAE . In AA and on antibody formation, rapamycin and cyclophosphamide were about equipotent, whereas methotrexate was more potent . The immunosuppressant activity of rapamycin appears to be related to inhibition of the lymphatic system.

J Pharm Sci, 1977 Feb, 66(2), 213 - 6
Rapid sensitive fluorometric analysis of cephalosporin antibiotics; Yu AB et al.; A rapid and sensitive fluorometric analysis for cephalosporins, which can also be applied to penicillins, is presented . The method involves reaction with 0.1 N sodium hydroxide at 100 degrees, producing stable fluorescent products . This method was applied to cephalexin and ampicillin with detection at concentrations as low as 0.01 mug/ml.

Am J Ophthalmol, 1977 Feb, 83(2), 198 - 205
Modification of the antibiotic system in M-K medium; Hull DS et al.; Corneal endothelial cell function and ultrastructure were studied in rabbit corneas stored in M-K medium with different antibiotics . At concentrations about ten times greater than their minimum inhibitory concentrations, tobramycin, gentamicin, polymixin B, penicillin and streptomycin mixture, cephaloridine, and cephalothin did not damage corneal endothelia . Corneas stored in M-K medium with bacitracin did not have temperature reversals as did other corneas after storage . This is probably not significant since they maintained almost constant thickness and the endothelial layer remained intact.

J Lab Clin Med, 1977 Feb, 89(2), 414 - 20
Human serum protein binding of cephalosporin antibiotics in vitro; Singhvi SM et al.; The published values for serum protein binding of antibiotics vary considerably depending upon the method and experimental conditions used . A rapid, simple, and standardized ultrafiltration procedure for determination of the serum protein binding of antibiotics has been developed and used to compare the binding characteristics of four marketed cephalosporins . The human serum protein binding of cephradine, cephalexin, cephalothin, and cefazolin at 37 degrees C . and physiological pH (7.4) was found to be 13.8, 12.4, 71.2, and 89.2 per cent, respectively . These values fall within the range of published values for these antibiotics.

No Shinkei Geka, 1977 Feb, 5(2), 137 - 43
{Clinical study on penetration of antibiotics into cerebrospinal fluid (second report),-Study on intravenous administration of sodium cephalothin with mannitol solution (author's transl)}; Takimoto N et al.; Penetration of Sodium Cephalothin (CET) into CSF follwing intravenous administration was studied in 23 patients with intracranial diseases excluding inflammation and severe subarachnoid hemorrhage . 1) After intravenous injection of 2 g of CET, ventricular CSF was obtained in 4 cases . All these 4 cases showed CET concentration in CSF to be below 0.1 mcg/ml . 2) After intravenous injection of 2 g of CET, lumbar CSF was obtained in 6 cases . In two cases out of these 6 cases, CET concentration in CSF was higher than 0.7 mcg/ml . 3) In 13 cases 2 g of CET with 200ml of 20% Mannitol was injected intravenously and lumbar CSF was examined . CET concentrations in CSF between 0.7 mcg/ml and 6.0 mcg/ml were observed in 9 cases of this group . 4) According to the results it is strongly suggested that the administration of Monnitol and CET is very effective for penetration of CET into CSF.

J Antibiot (Tokyo), 1977 Feb, 30(2), 132 - 40
Biochemical study of minosaminomycin in relation to the kasugamycin group antibiotics; Suzukake K et al.; Minosaminomycin is structurally related to kasugamycin and inhibits protein synthesis in mycobacteria . It also inhibits phage f2 RNA-directed protein synthesis in a cell-free system of Escherichia coli by 50% at 2 x 10(-7) M . It is 100-times more potent than kasugamycin in this system . At 10(-7) M minosaminomycin inhibits EF-T dependent binding of aminoacyl-tRNA to ribosomes by 50% . This effect is markedly diminished if minosaminomycin is added to the assay system after a brief incubation of ribosomes with mRNA . Like kasugamycin, minosaminomycin preferentially inhibits the initiation of protein synthesis directed by phage f2 RNA in vitro and does not cause miscoding . Ribosomes from kasugamycin-resistant mutants Ksg A and Ksg C were as sensitive to minosaminomycin as those from each parent strain . In spite of the strong inhibitory activity of minosaminomycin manifested in cell-free systems of E . coli, this compound inhibits the growth of the organism itself only slightly . This discrepancy could be ascribed to impermeability, as E . coli cells with modified permeability show greater sensitivity to minosaminomycin . There is no indication that the antibiotic is activated in E . coli cells . On the basis of these results, the structural features of these antibiotics is inactivated in E . coli cells . On the basis of these results, the structural features of these antibiotics essential for interaction with ribosomes and for permeability into the cells are discussed.

J Antibiot (Tokyo), 1977 Feb, 30(2), 158 - 62
Polyene antibiotics . IX . An improved method for the preparation of methyl esters of polyene antibiotics; Pandey RC et al.; An improved general method for the preparation of methyl esters of polyene antibiotics is discussed . Using this method methyl esters of pimaricin, nystatin, eurocidin, hamycin, hamycins A and B, aureofungin, partricins A and B, candimycin, candicidin, and amphotericin B have been prepared and their physical properties are reported . The biological activities of hamycins A and B and their methyl esters are also described.

Aust N Z J Surg, 1977 Feb, 47(1), 105 - 7
The optimum duration of systemic antibiotic administration in the treatment of experimental peritonitis; Law D et al.; The duration of antibiotic therapy for peritonitis is commonly decided on an empirical basis . There is obvious advantage in determining the shortest, yet most effective, period for such drug therapy . This study is a comparison of short-course and long-course antibiotic administration following periotonitis produced by experimental rupture of the rabbit appendix.

Circulation, 1977 Feb, 55(2), 353 - 61
Six year review of the results of freehand aortic valve replacement using an antibiotic sterilized homograft valve; Barratt-Boyes BG et al.; The long-term behavior of an antibiotic-treated homograft aortic valve inserted in a freehand fashion was assessed in 121 patients operated upon for aortic valve disease and followed from four to six and one-half years . There were seven hospital deaths (5.7%) and 30 late deaths, only one of which was related to the homograft valve . The six year survival was 69% (77% for single valve and 52% for multiple valve surgery) . At six years 9% had important homograft aortic valve incompetence (HAVI) and most of these required reoperation . Important HAVI occurred in only 5% of patients with an aortic root diameter less than 24 mm and in 38% of those with a markedly dilated or distorted proximal aorta (P less than 0.01) . The freehand aortic homograft was considered superior to prosthetic devices because of the absence of chronic anticoagulation, thromboembolism, sudden death from valve failure and significant obstruction in a small aortic root . With slightly restricted patient selection the valve failure rate is expected to fall to less than 1% per year.

Science, 1977 Jan 28, 195(4276), 400 - 2
Reverse banding on chromosomes produced by a guanosine-cytosine specific DNA binding antibiotic: olivomycin; van de Sande JH et al.; Characteristic reverse fluorescent banding patterns (R bands) on human, bovine, and mouse metaphase chromosomes are produced by treating chromosome preparations directly with olivomycin . With the DNA in solution, the repeating polymer poly{d(G-C)} - poly{d((G-C)} (where G is guanine and C is cytosine) enhanced the fluorescence of olivomycin, while the antibotic fluorescence was not affected by the alternating polynucleotide poly}d(A-T)} - poly{d(A-T)} (where A is adenine and T is thymine) . Calf thymus DNA, with an intermediate G-C content of about 40 percent, showed a smaller fluorescence enhancement in the presence of olivomycin as was observed for the synthetic polynucleotide poly{d(G-C)} - poly {d(G-C)} . The closely related antibiotic chromomycin A3 showed the same results as were obtained with olivomycin either in the solution interaction with specific DNA's or with the netaphase chromosome preparations . The production of R bands by these G-C-specific DNA binding antibiotics lends credence to the suggestion that the arrangement of the nucleotide sequences along the chromosome is a primary determinant for the appearance of fluorescent bands.

Can Med Assoc J, 1977 Jan 22, 116(2), 162 - 3
Antibiotic-associated pseudomembranous colitis; Bartle WR et al.; Two cases of pseudomembranous colitis, one associated with administration of ampicillin and the other associated with administration of ampicillin and trimethoprim-sulfamethoxazole, are reported . Both patients presented with diarrhea, abdominal pain, fever and an elevated leukocyte count . Pseudomembranous colitis was diagnosed by sigmoidoscopy and biopsy . Both patients recovered with conservative management.

Folia Microbiol (Praha), 1977, 22(5), 321 - 8
Strain improvement in Streptomyces galilaeus, a producer of anthracycline antibiotics galirubins; Kralovocova E et al.; The production of epsilon-pyrromycinone glycosides in Streptomyces galilaeus increased 12-fold, with respect to the wild strain, as a result of a sequential procedure including both natural selection and treatment with mutagens (nitrous acid, UV light and gamma-irradiation) . Nitrous acid exhibited the highest mutagenic effect, both in increasing the productivity and in inducing blocked mutants . A mutant strain blocked in the biosynthesis of glycosides and accumulating free epsilon-pyrromycinone as the principal metabolite was obtained.

Ophthalmologica, 1977, 174(6), 301 - 9
Reconstruction of the orbit with antibiotic acrylic in cases of severe bone loss; Frezzotti R et al.; The advantages of using antibiotic acrylic resin in the reconstruction of the orbit following injury or tumor removal are described . Four cases are presented whose long-term results confirm the value of the new method.

Int J Pept Protein Res, 1977, 10(1), 51 - 9
Theoretical studies on beta-lactam antibiotics . I . Conformational similarity of penicillins and cephalosporins to X-D-alanyl-D-alanine and correlation of their structure with activity; Virudachalam R et al.; The substrate analogue hypothesis proposed for the mechanism of the action of penicillins and cephalosporins is examined by stereochemical criteria . These beta-lactam antibiotics assume conformation similar to X-D-alanyl-D-alanine due to the presence of the lactam ring; this disagrees with the assumption made by Tipper & Strominger that L and D amino acid residues take similar conformation . The model proposed in this study for the activity of these antibiotics differs considerably from the earlier models, mainly in phi2 rotational angle which determines the conformation of the aminoacyl group . The inactivity of C6 or C7 epimers and the effect of various substitutions at 6alpha or 7alpha and C2 positions of penicillins and cephalosporins on the biological activity are explained.

Infection, 1977, 5(2), 123 - 5
{Enzymatic assays of aminoglycoside antibiotics (author's transl)}; Kayser FH; Adenylylating or acetylating enzymes, which are produced by grampositive and gramnegative bacteria resistant to aminoglycoside antibiotics, are useful tools in determining concentrations of aminoglycosides in patients' body fluids . Due to their accuracy, stability, versatility, fastness and inexpensiveness, enzymatic assays are the tests of choice for the routine determination of aminoglycoside concentrations.

Z Allg Mikrobiol, 1977, 17(3), 227 - 34
{Lambdamycin, an antibiotic from strain IMET 31118 of Streptomyces glaucoachromogenes Prauser . II . Physiochemical properties and comparison with chartreusin}; Strauss DG et al.; The isolation and purification of the antibiotic lambdamycin are described . The physicochemical properties of the chromoglysoide lambdamycin resemble those of chartreusin . In this paper we compare the physicochemical properties of chartreusin and antibiotic X 465 with lambdamycin (alpha D, UV, IR) . Lambdamycin is identified with chartreusin.

Antibiotiki, 1977, 22(2), 150 - 3
{Distribution of polyene antibiotics in the cells of a tissue culture of puppy kidney}; Kravchenko LS et al.; The results of the studies on interacellular distribution of amphotericin AM-2, a wate soluble derivative of amphotericin in the cells of the puppy kidney tissue culture exposed to the antibiotic in a concentration of 50 gamma per 1 ml medium for 17 hours are presented . It was found that the antibiotic was firmly bound with the kidney cells: 15.4 per cent of the initial amount of the antibiotic was detected in the washed cells . Analysis of the antibiotic distribution in separate subcellular components showed that sorption of amphotericin AM-2 by the plasmic membranes, nuclei and cytoplasm was respectively 18.3, 35.6 and 9.7 per cent of the amount absorbed by the cells . Binding of a significant amount of the antibiotic absorbed by the plasmic membranes and nuclei with the above fractions was reversible . The results of the study provided a supposition that amphotericin AM-2 penetrated into the cells of the kidney tissue which adds some new findings to the studies on the mechanism of action of polyenic antibiotics in cells.

Mikrobiologiia, 1977 Jan-Feb, 46(1), 80 - 5
{Effect of colchicine and other polyploidogenic factors in contact with the deep vegetative mycelium of the fungus Trichothecium roseum--producer of the antibiotic trichothecin and proteolytic enzymes}; Maksimova RA et al.; Colchicine, boric acid, and camphor were used to produce viable cultures of Trichothecium roseum actively producing the antibiotic, by treating the submerged vegetative mycelium of the fungus with these compounds . Colchicine (0.5--1.0%), boric acid (0.25--2.00%), and camphor (0.25--1.50%) were added to the nutrient medium before it was inoculated with conidia or vegetative mycelium; later, the submerged mycelium was transferred to slanted agar . The cultures were characterized by a high number of the nuclei in the conidia, a low ratio of the plasma to the nuclei, a high rate of growth, and a high antibiotic activity . In sharply varying conditions of nutrition, such polynuclear forms had an adaptive advantage as compared to the parent forms . The polynuclear cultures are regarded to be biologically equal to polyploid forms.

Neoplasma, 1977, 24, 239 - 42
Different sensitivity to antibiotics of the established intermitent in vivo--in vitro tumor cell lines in comparison with the primary cultures; Fuskova A et al.; From original strains of tumors growing only in vivo (I) new lines of strains (II) were obtained, the cells of which proliferated readily both in vitro and in vivo . Sensitivity in all the new strains (II) generally increased but in varying degrees as against individual cancerostatic drugs, as evident from the given ID50 values and sensitivity indices . In addition to an enhanced sensitivity of the strains to inhibitors, their ability to utilize precursors of the synthesis of nucleic acids and proteins in a linear dependence during the course of 24 hours has also been determined.

Urologe A, 1977 Jan, 16(1), 39 - 42
{The distribution of antibiotics in extravascular renal tissue during experimental pyelonephritis of dogs (author's transl)}; Djulepa J et al.; For the success of an antibiotic therapy in pyelonephritis the concentration of antibiotics attainable in the kidney tissue is of extreme importance . Therefore in dogs, besides serum level and urin level a tissue level was defined after a single dose of gentamycin and cefazolin . While gentamycin is highly concentrated in the kidney, which is indeed more in a state of shock than health, Cefalozin is being excreted, after initially high values, excreted in a course approximately parallel to the blood level curve, within 5 h down to concentrations between 1 mcg/ml and 4 mcg/ml . The level of the tissue in the cortex of healthy kidneys and infected kidneys without additional damage by a ureter ligature averaged about 40% less than the serum level . The tissue level of kidneys infected by the additional damage of a ureter ligature and with signs of a pyelonephritis was extremely lower and reached occasionally hardly 20% of the serum level . Attention is also called to the consequence of these results for the therapy of the pyelonephritis.

Avian Dis, 1977 Jan-Mar, 21(1), 57 - 68
Antibiotic egg injection to eliminate disease . I . Effect of injection methods on turkey hatchability and Mycoplasma meleagridis infection; McCapes RH et al.; Mycoplasma meleagridis infection in turkey hatching eggs was eliminated by injecting eggs with a combination of tylosin and gentamicin . Hatched F1 and F2 progeny remained free of egg-transmitted infection . Contact exposure was experienced in one negative flock . Of the preincubation injection procedures studied, a drilled hole on the small end of the egg was the inoculation site easiest to administer and best tolerated by the embryo . The embryo can tolerate a dose of gentamicin sulfate injected at 10 days of incubation that would be toxic if administered before incubation . Requirements for maintaining progeny free of infection are discussed.

Antibiotiki, 1977 Jan, 22(1), 33 - 6
{Method of the spectrophotometric analysis of polyene antibiotics}; Lupashevskaia DP et al.; The method of quantitative spectrophotometric analysis of several substances in the presence of admixtures is described . The method is based on presentation of an unknown spectrum of the admixture absorption by the polyen of the 3rd or 4th power depending on the wave length . The optical density of the mixture of any wave length is expressed by the linear equation, including the Firord equation for the known components and the given polynome . The system of such equations for 10-15 analytical wave lengths may be solved with the method of the least squares using an electronic computer . The system solvations are the concentrations of the mixture components to be determined and the polynome coefficients . The method was tested on model mixtures composed of amphotercin B, myocheptin, nystatin and griseofulvin, as well as of isomeric nitroanilines playing the role of the admixture . The analysis error for the compounds of the polyenic structure having not less than 2 absorption maxima in the given spectral ranges did not exceed 1-3 per cent . As for the compounds with a single maximum or when the admixture included also polyenic compounds the analysis error increased up to 6--50 per cent.

J Wildl Dis, 1977 Jan, 13(1), 49 - 54
Intratracheal injection of antibiotics in the California sea lion, Zalophus californianus, and bottlenosed dolphin, Tursiops truncatus; Sweeney JC; Gentamicin and cephaloridine were administered by intratracheal injection to the California sea lion, Zalophus californianus, and the bottlenosed dolphin, Tursiops truncatus . Uptake and clearance of these antibiotics in the blood were monitored . In all cases, absorption through the respiratory mucosa resulted in blood levels approaching therapeutic concentrations despite low dosages.

J Antibiot (Tokyo), 1977 Jan, 30(1), 31 - 8
A new aminoglycoside antibiotic complex--the seldomycins . III . The structures of seldomycin factors 1 and 2+; Egan RS et al.; The structures of seldomycin factors 1 and 2 have been determined by consideration of chemical degradation and spectral properties . Factor 1, also known as XK-88-1, is shown to be 6-O-(2-amino-2-deoxy-alpha-D-xylopyranosyl) paromamine (1) and factor 2, also known as XK-88-2, is shown to be 4'-deoxy-neamine (2) . Mass spectral evidence has been obtained that suggests the most probable structure for seldomycin factor 3, also known as XK-88-3, is 6'-amino-6'-deoxyseldomycin factor 1 (12).

J Antibiot (Tokyo), 1977 Jan, 30(1), 11 - 6
Isolation and characterization of a new nucleoside antibiotic, amipurimycin; Harada S et al.; A new antibiotic amipurimycin, active against Pyricularia oryzae in vitro and in vivo, was isolated from the culture filtrate of Streptomyces novoguineensis nov . sp . The antibiotic was purified by a combination of ion-exchange and adsorption chromatography based on its amphoteric water-soluble characteristics . Its molecular formula was estimated to be C20H27approximately31N7O8-H2O . Characteristic maxima in the UV spectrum and signals in the PMR and CMR spectra were similar to those of 2-aminopurine 9-(beta-D)-riboside . These findings indicated that amipurimycin is a new nucleoside antibiotic and the first example of a natural product containing 2-aminopurine.

Monatsschr Kinderheilkd, 1977 Jan, 125(1), 16 - 21
{Follow up of children treated with antibiotics (author's transl)}; Daschner F; Follow up of children treated with antibiotics should include survey of the patient (clinical response, pharmakokinetics, therapy compliance, side effects), the infecting organism (elimination, change of causative organisms, changes in hospital flora), as well as the host-parasite relationship (changing flora in the patients, incompatibilities, defects of the cellular or humoral defense mechanisms).

J Pharmacol Exp Ther, 1977 Jan, 200(1), 195 - 206
The cardiovascular pharmacology of the antibiotic ionophore Ro 2-2985 (X537A); Osborne MW et al.; Ro 2-2985 increased mean arterial blood pressure in both the venous bypass preparation and the intact animal; however, total peripheral resistance increased in the venous bypass preparation with a constant cardiac output but decreased in the intact animal with an increase in cardiac output . These observations indicate a drug-related increase in the distensibility of the aorta at the same arterial pressure . In vivo ventricular function curves were shifted to the left indicating enhanced myocardial performance with the translocation of large volumes of blood to the central circulation since total body venous compliance was significantly decreased . Beta adrenergic blocking doses of propranolol blocked the positive inotropic effect of Ro 2-2985 while myocardial depression produced by toxic doses of propranolol was reversed . This observation suggests several mechanisms for the Ro 2-2985 metabolic mediation of myocardial muscle contraction . The cardiovascular effects produced by Ro 2-2985 were accompanied by a marked polycythemia and a decrease in plasma volume without a change in total circulating blood volume, while blood glucose values showed a nonsignificant increase . Ro 2-2985 produced a marked increase in cardiac output . The increase in myocardial performance appears to be complex since myocardial force of contraction, dT/dt, dP/dt:P40 and Vmax were all increased . RO 2-2985 increased coronary flow without an increase in resistance . There were no significant increases in myocardial arteriovenous glucose, lactate, K+, Ca++, Na+ or Cl.

Clin Pediatr (Phila), 1977 Jan, 16(1), 60 - 3
Minocycline in the antibiotic regimen of cystic fibrosis patients: weight gain and clinical improvement; Patterson PR; Minocycline hydrochloride was given to 100 patients with cystic fibrosis of the pancreas for periods of 3 months over a broad-spectrum antibiotic drug rotation which lasted 2 years . Increased weight gain and some clinical improvement was seen during treatment with minocycline . Those patients with severe disease gained more weight than those with mild or moderate disease, and males gained more than females . When minocycline hydrochloride was not the drug in use, patients lost weight and their health declined.

Biochimie, 1977, 59(11-12), 927 - 32
{Partial synthesis of aminoglycosidic antibiotics . I . An enzymatic reactor model using cofactors}; Le Goffic F et al.; In order to produce specifically N-monoalkylated derivatives of aminoglycoside antibiotics of potential therapeutic values, we have developed an enzymatic reactor . This system uses the aminoglycoside acetyltransferase as catalyst and acetylcoenzyme A as acetyl donor . The immobilization of one aminoglycoside acetyltransferase on different resins has been studied . The coreticulation of this enzyme on DEAE cellulose in the presence of glutaraldehyde gives rise to an enzymatic resin of high efficiency . On the other hand, we have also studied the acetylation of coenzyme A in a simple manner . Acetylation occurs in a quantitative yield when the reaction is performed in the presence of polyvinyl-4 pyridine/divinylbenzene 2 per cent . These conclusions enabled to develop two types of acetylating reactors which give rise without purification to 3-acetyl gentamicin.

Arzneimittelforschung, 1977, 27(1), 141 - 3
The neuromuscular blocking activity of aminodeoxykanamycin as compared with that of other aminoglycoside antibiotics; Paradelis AG et al.; Aminodeoxykanamycin (Kaneudomycin) as well as other members of the aminoglycoside antibiotics, has an action at the neuromuscular junction . Kanendomycin was found to be five times less potent than gentamycin, as far as their neuromuscular blocking action on the rat diaphragm is concerned . The neuromuscular blocking action on the rat diaphragm is concerned . The neuromuscular blockade produced by Kanendomycin is not reversed by neostigmine but only by calcium chloride.

Arch Immunol Ther Exp (Warsz), 1977, 25(6), 757 - 64
Antibiotics produced by Streptomyces olivaceus 142 . III . Influence of antibiotic Wr 142 FPG on development of transplantable tumors in mice; Mordarski M et al.; The action of two preparations (I and II) of antibiotic Wr 142 FPG on development of Ehrlich carcinoma, Nemeth-Kellner lymphoma and leukemias L 1210 and P 388 was studied . Preparation I injected s.c . daily during 14 days in doses of 10 mg/kg (1/25 LD50) inhibited growth of Ehrlich carcinoma and Nemeth-Kellner lymphoma subcutaneous tumors in R 3 mice by about 70% . The same preparation in a single i.p . injection (10 mg/kg) in FDF1 mice distinctly prolonged survival of mice inoculated with L 1210 leukemia, but was without effect on P 388 leukemia . Preparation II inhibited growth of solid tumors in doses as low as 0.1-0.2 mg/kg (about 65% inhibition), but in the same doses was ineffective against leukemias L 1210 and P 388 in CDF1 mice.

Am J Med Sci, 1977 Jan-Feb, 273(1), 79 - 85
The effect of an educational program upon hospital antibiotic use; Jones SR et al.; The effect of an educational program on the use of antibiotics was studied in a university-affiliated Veterans Administration Hospital . Following an initial survey of antibiotic usage, educational presentations of the collected data were made to the hospital staff which included specific prescribing errors and alternative recommendations . Then, another survey was conducted . Measurable changes following the educational presentations were limited to decreasing costs of unjustified antibiotic use . An effect was noted in decreasing unjustified use of antibiotics in prophylactic situations, but this remained the most common misuse . Thus, an educational program directed at specific prescribing errors produced little noticeable effect on the use of antibiotics in a university-affiliated hospital . The study indicates that more direct measures, such as control of use of particular antibiotics, may be required to produce a meaningful change in prescribing practices.

Arzneimittelforschung, 1977, 27(12), 2314 - 6
{Antibiotic therapy with doxycycline in dogs with lung transplantations (author's transl)}; Keiler A et al.; In contrast with kidney, heart and liver transplantations, lung transplantation involves an organ which has contact with the environment and bears a special risk of infection . This circumstance and the diminished resistance during immunosuppressive therapy makes long-term treatment with an effective broad-spectrum antibiotic advisable for lung transplantations . Taking into consideration the different objectives and questions within the research project concerned the 182 lung allotransplantations carried out in dogs can be divided into two therapeutic groups in regard to postoperative treatment: lung allotransplantations with and without immunosuppressive therapy (methylprednisolone, azathioprine) . Long-term doxycycline therapy was carried out in both groups . Those animals which were not treated with immunosuppressive drugs survived for an average of 9 days, those receiving immunosuppressive therapy survived for an average of 30 days . The longest survival period was 2.5 years . Clinically and histologically it could be demonstrated that doxycycline was successful both during the immediate postoperative period and in antibiotic long-term therapy after experimental lung transplantations.

Arch Immunol Ther Exp (Warsz), 1977, 25(3), 409 - 22
The influence of antibiotics WR 142 on permeability of cell membranes; Jaworska-Blach B; The influence of antibiotics WR 142 (fractions I and II and Wr 142 FPG) on transport across cell membranes of B . subtilis and C . albicans was studied . Antibiotics Wr 142 did not increase permeability of cell membranes as 86Rb was not exchanged by other monovalent ions in the presence of the antibiotic preparations . Temperature, ionic strength and pH had no significant influence on the action of these antibiotics on the cell membranes . Antibiotics Wr 142 do not form lipid-soluble complexes with alkali metal ions, and therefore do not transport these ions, in contrast to the ionophoric antibiotics . No effect of antibiotics Wr 142 on the stucture of the cell membrane depriving it of its selective function as an osmotic barrier was observed.

Med Cutan Ibero Lat Am, 1977, 5(2), 135 - 50
{Analysis of delayed hypersensitivity to antibiotics}; Mansur MC et al.; The delayed hypersensitivity to antibiotics existing in Brazil, including the systemically administered, is analyzed . The sulphanilamide, penicillin, neomycin, oxacillin, oxitetraciclyne, chloramphenicol and kanamycin were the more positive to the contact test . We do not find any difference in the test between sex and race . The positivity was 7,5 times higher in adults than in children . In spite the high positivity in atopic patients we could not demonstrate the same in patients with other allergic procesus history.

Acta Orthop Scand, 1977, 48(4), 405 - 10
Prophylactic antibiotics against early and late deep infections after total hip replacements; Carlsson AK et al.; A review with a longer observation period is performed of a previously published double-blind investigation of the prophylatic value of cloxacillin against late infections after total hip replacements; In addition, a retrospective patient material is examined . The total material consisted of 1065 total hips . 15.4 per cent deep, late infections were found in the group without prophylaxis and 20 per cent in the one with prophylaxis . The frequency of haematogenous deep infection was estimated to be less than 1 per cent.

Folia Microbiol (Praha), 1977, 22(4), 303 - 7
Antifungal antibiotic of the Basidiomycete Oudemansiella mucida . III . Nuclei in the hyphae of mono- and dikaryons; Semerdzieva M et al.; Nuclear ratios were studied in terminal and subterminal cells of various mycelia of the basidiomycete Oudemansiella mucida, the producer of the antifungal antibiotic mucidin (MuciderminR Spofa) . The dikaryon, the monokaryon, and the mucidin-producing strain that had been cultivated for a long time under submerged conditions were compared . Dedikaryotization was found to have taken place in the producing strain . The originally dikaryotic culture with characteristic clamp connections on the mycelium and with two nuclei in every hyphal cell lost permanently the clamp connections, probably owing to continuous intense agitation . The hyphae contained solely mononuclear cells . Mating with a compatible monokaryon yielded a dikaryon capable of normal fructification.

Folia Microbiol (Praha), 1977, 22(4), 298 - 302
Antifungal antibiotic of the Basidiomycete Oudemansiella mucida . II . Life cycle and fructification of the producing fungus; Musilek V et al.; The developmental cycle of the fungus Oudemansiella mucida, the producer of a new antifungal antibiotic, was found to be controlled by the mechanism of homogenic tetrapolar incompatibility; under our conditions, the cycle took about 12 weeks to completion . Optimum conditions for a laboratory-scale fructification were investigated . Normal fruiting body formation required sufficient illumination, temperatures below 20 degrees C, and relative humidity in excess of 70% . Flask-grown fruiting bodies did not differ from the naturally occurring ones . The basidiospores of the produced fruiting bodies yielded the reference monokaryons necessary for physiological, cytological and genetical studies.

Antibiotiki, 1977, 22(2), 168 - 72
{Effect of the peroral use of the antitumor antibiotic, carminomycin, on the immunological reactivity of the body of animals}; Shapovalova SP et al.; Carminomycin administered orally to mice for many times in doses of 2.5 and 1.25 mg/kg induced suppression of hemagglutinine production to sheep erythrocytes and formation of immunologically competent cells in the spleen of test animals . The content of DNA and RNA in the spleen of the test animals treated with carminomycin and sheep erythrocytes was somewhat lower than that in the control mice immunized but not treated with the antibiotic . Carminomycin prolongated the life time of the skin graft by 6.5 days as compared to that of the skin homotransplant in the control animals . The oral use of carminomycin in a dose of 2.5 mg/kg induced a statistically significant decrease in the absorption capacity of the cells of the reticuloendothelial system of the animals.

J Antibiot (Tokyo), 1977 Jan, 30(1), 88 - 97
Mutational biosynthesis by idiotrophs of Micromonospora purpurea . I . Conversion of aminocyclitols to new aminoglycoside antibiotics; Rosi D et al.; By mutation and strain improvement techniques idiotrophs of Micromonospora purpurea, the gentamicin-producing organism, were obtained which require an exogenous source of 2-deoxystreptamine in order to produce gentamicin . Streptamine incorporation afforded a mixture of 2-hydroxygentamicin C as a complex of essentially the C1 and C2 components whereas 2-deoxystreptamine when incorporated by the same idiotroph afforded the same mixture of C1, C2 and C1a gentamicins as the parent (m1) organism . The 2-hydroxygentamicin C complex exhibited broad-spectrum antibiotic activity with an in vitro potency less than that for the gentamicin C complex, but with greater activity against selected gentamicin C resistant organisms . The LD 50 (i.v.) in mice of the 2-hydroxygentamicin C complex indicated that it had approximately half the toxicity of the gentamicin C complex . 2, 5-Dideoxystreptamine affordeda C1, C2, and C1a mixture of 5-deoxygentamicins, which also had broad spectrum activity, and exhibited improved activity against several gentamicin-acetylating strains of resistant bacteria . The LD50 (i.v.) in mice of the 5-deoxygentamicin C complex indicated that it was about 2.5 times more toxic than the gentamicin C complex . Two derivatives of 2,5-dideoxystreptamine afforded the same mixture of 5-deoxygentamicins . 2-Epistreptamine upon supplementation to a broth containing growing cultures of these idiotrophs also produced antibiotic.

Chemotherapy, 1977, 23 Suppl 1, 82 - 5
Combined action of fosfomycin with beta-lactam and aminoglycoside antibiotics; Borowski J et al.; The combined action of fosfomycin with penicillin G, ampicillin and streptomycin was investigated . A total of 11 S . aureus and 10 E . coli were included in these studies . It has been shown that a combination of fosfomycin with penicillin G and streptomycin resulted in a synergistic effect . When S . aureus strains were tested, the combination of fosfomycin with penicillin G was more frequently effective than the combination of fosfomycin with streptomycin . The combinations of fosfomycin with ampicillin and streptomycin showed a similar synergistic effect on 7 of 10 E . coli strains . The antagonistic effect never resulted when the above-mentioned combination of antibiotics were used . The authors postulate that a combination of fosfomycin with beta-lactam or aminoglycoside antibiotics may be used in clinical practice and such a procedure should prevent an emergence of fosfomycin-resistant strains.

J Lab Clin Med, 1977 Jan, 89(1), 65 - 71
Alteration of effectiveness of antibiotics by anaerobiosis; Verklin RM Jr et al.; In vitro antibiotic susceptibility tests of facultative organisms are routinely performed under aerobic conditions, despite the fact that many infections caused by these organisms occur in anaerobic areas, i.e., intra-abdominal absess . Experiments were performed aerobically and anaerobically to determine the susceptibility of E . coli, P . mirabilis, and K . pneumoniae to gentamicin, tobramycin, cephalothin, cefazolin, and cefamandole . Antibiotic sensitivities were determined by disc and agar dilution techniques in air and in anaerobic jars with CO2 absorbed . Tube dilution studies were performed in air and anaerobically and time-kill studies were done in aerobic and anaerobic broth . The amount of aminoglycoside required to inhibit bacterial growth was increased 4 to 20 times by anaerobiosis in 20 of 25 strains tested . Time-kill curves showed that bacterial killing by aminoglycosides was markedly impaired by anaerobiosis . Anaerobic conditions had no effect on the rate or extent of killing by cephalosporins . These data may have significance in determination of antibiotic susceptibility of facultative organisms under anaerobic tissue conditions . Antibiotic sensitivity testing done on these organisms in air may not reflect the actual state of antibiotic-bacterial interaction under conditions of the infection.

Annu Rev Biochem, 1977, 46, 723 - 63
Polymyxin and related peptide antibiotics; Storm DR et al.; The general mechanism for the antibiotic activities of the polymyxins and octapeptins has been elucidated by research using a broad range of experimental techniques . However, this phenomenon has not been described in detailed molecular terms, and this must be one of the major goals for future research in this area . Since 1947, when polymyxin was first isolated, there have been tremendous advances in our knowledge of membrane structure . The application of biophysical technology such as NMR, ESR, fluorescence spectroscopy, differential scanning calorimetry, and electron microscopy has been particularly valuable for studying model and biological membrane structures . It is these techniques which will provide a detailed molecular mechanism for the effects of these peptide antibiotics on membrane structure . In addition, the large number of antibiotic derivatives available should be exploited more extensively for structure-function correlations . The ultimate goal is to correlate the biological properties of these peptides with their effects on the physical properties of membranes and to rationalize these events in terms of lipid-peptide interactions.

Antibiotiki, 1977 Jan, 22(1), 60 - 4
{Some ways to eliminate the side effects of antibiotic therapy in experimental pneumonia}; Anikeeva SP et al.; Impairement in the process of tissue respiration at the subcellular level in growing animals with experimental pneumonia are described . Under the conditions of antibiotic therapy such impairements aggravated . A combined use of antibiotics with succinic and glutamic acids resulted in improvement of the tissue respiration and acceleration of reparation . Possible mechanisms of this phenomenon are discussed.

Antibiotiki, 1977 Jan, 22(1), 7 - 13
{Streptoverticillium albireticuli var . kokandum, a producer of the new antifungal pentaene antibiotic, kokandomycin}; Konev IuE et al.; Morphological, cultural and physiological properties of actinomycete L10-0208 were studied . It was shown that actinomycete was a new natural variant . It was named Streptoverticillium alboreticuli var . kokandum . The physico-chemical characteristics of the pentaenic antibiotic are presented and its originality is shown . The antibiotic is named kokandomycin.

Laryngol Rhinol Otol (Stuttg), 1977 Jan, 56(1), 40 - 9
{Damage of the cochlea and of the cochlear nucleus after the application of aminoglycosid antibiotics--a comparative light-, transmission- and scanning electronmicroscopic study in the guinea pig (author's transl)}; Theopold HM; Ototoxic alterations were studied in the guinea pig organ of Corti and in the cochlear nucleus after high administrations of aminoglycosid antibiotics (Gentamicin/Tobramycin, 150 mg/kg body weight/day or Amikacin 300 mg/kg body weight for 10 days) . After survival times up to 22 days the animals were examined . By means of morphology degeneration was found in the cochlear nucleus before we could state it in the organ of Corti . After longer survival times, when we observed heavy degeneration in the organ of Corti we found only a few myelin figures of axons in the cochlear nerve . Cochlear nucleus: As an early sign of degeneration alterations in the mitochondria were found . Compared with the organ of Corti the damage was less widespread in the second order neurons of the afferent auditory pathways, their dendrites or nerve endings . Quantitative calculations however, were not performed . In axosomatic synapses we could observe a way of degeneration which was not reported before in damage caused by aminoglycosid antibiotics . Free postsynaptic densities were observed to be invaginated into the neuron as a probable way of sequestration . As well we could observe reoccupation of the synaptic sites by a probable sliding of neighbouring nerve endings into the free intracellular space . (Similar observations were reported first by Gentschev and Sotelo {1973} after ablation of the cochlear nerve in rats.

J Bacteriol, 1977 Jan, 129(1), 81 - 6
Relationship between changes in the translational apparatus and actinomycin production in Streptomyces antibioticus; Jones GH; As previously reported (G . H . Jones, 1975), transfer ribonucleic acids (tRNA's) and ribosomes from actinomycin-producing cultures of Streptomyces antibioticus show a decreased ability to function in aminoacylation and translation as compared with the corresponding components from younger cells . Further, specific changes in the isoacceptor patterns are revealed when tRNA's from actinomycin-producing cells are compared with those of younger cells by reverse- phase column chromatography . A specific glycyl-tRNA species is eliminated from the reverse-phase profile of tRNA's from actinomycin-producing S . antibioticus cells as compared with younger cells . Changes in isoacceptor patterns were also observed for the amino acids methionine, valine, phenylalanine, and leucine . Actinomycin synthesis was inhibited by growing S . antibioticus cells in the presence of alpha-methyl-DL-tryptophan . Inhibition of actinomycin synthesis reversed the changes in tRNA observed in normally grown control cultures, although it had no demonstrable effect on the growth of the cells . Thus, tRNA from 48-h-old, alpha-methyl-tryptophan-grown cells had amino acid acceptor activity that was equal to or greater than that of tRNA from 12-h-old, normally grown cells . Similarly, the reverse-phase chromatographic pattern for glycyl-tRNA's from 48-h-old, alpha-methyl-tryptophan-grown cells was identical to that of the glycyl-tRNA's from 12-h-old, normally grown cells . In contrast, the ability of ribosomes from 48-h-old, alpha-methyl-tryptophan-grown cells to function in polypeptide synthesis in vitro was essentially identical to that of 48-h-old, normally grown cells . Ribosomes from 12-h-old, normally grown cells were severalfold more active in in vitro polypeptide synthesis.

J Biochem (Tokyo), 1977 Jan, 81(1), 25 - 35
Spontaneous deamidation of a protein antibiotic, neocarzinostatin, at weakly acidic pH . Conversion to a homologous inactive preneocarzinostatin due to change of asparagine 83 to aspartic acid 83 accompanied by conformational and biological alterations; Maeda H et al.; The amide content of neocarzinostatin (NCS), an antitumor protein, has been determined by analysing asparagine and glutamine in the Pronase-aminopeptidase M digests of tetra-S-carboxymethyl-NCS and carboxyl-modified NCS (modified with a water-soluble carbodiimide and {14C}glycine methyl ester) . Preneocarzinostatin (PRE) was separated and purified from a crude NCS preparation by CM-cellulose column chromatography . PRE was found to contain one mole less asparagine than NCS, and asparagine was deamidated to aspartic acid in PRE . A time-dependent conversion of NCS to PRE at pH 3.2 at 4 degrees or in 0.1 M acetic acid at 26 degrees was studied in two ways; first, by quantitative determination of NCS and PRE by CM-cellulose column chromatography and second, by following the release of free NH3 during dialysis in an air-tight container . Within experimental error, PRE was indistinguishable from NCS in amino acid content after acid hydrolysis, as well as in apparent molecular weight as determined by SDS-disc gel electrophoresis (10% acrylamide), and N- and C-terminal amino acid residues . Both NCS and PRE shared a common antigenicity as determined by Ouchterlony's agar diffusion method . Only a slight difference between the two in electrophoresis on a cellulose acetate membrane and on a peptide map of the tryptic digest was demonstrated . PRE, however, was completely devoid of biological activity . In addition to the chromatographic difference, a conformational difference was observed by CD spectroscopy, namely, an apparently looser structure of PRE was indicated by the shallowness of the trough in the 240-265 nm region . This interpretation was supported by the finding that digestions by Pronase were more extensive with PRE than with NCS . These results indicate an important role of the single asparagine residue (Asn 83) of NCS in the biological activity, which is evidently governed by the conformation.

Biochim Biophys Acta, 1976 Dec 14, 455(3), 961 - 72
Stoichiometry of hemolysis by the polyene antibiotic lucensomycin; Strom R et al.; The stoichiometry of hemolysis by the polyene antibiotic lucensomycin was investigated . It appears that hemolysis occurs only when a relatively high fraction (probably between 15 and 40%) of the cholesterol sites in the erythrocyte membrane have combined with the polyene . Also in phospholipid-cholesterol vesicles the increase of permeability requires occupancy of 40-50% of the existing cholesterol sites . As for the possible cooperative effect in the hemolytic process, it is probable that several (at least 9-10) lucensomycin-cholesterol adducts must interact on each side of the membrane to form an aqueous channel; the distribution of these adducts in the erythrocyte membrane occurs, however, apparently at random.

Minerva Med, 1976 Dec 8, 67(60), 3987 - 96
{Problems in the use of antibiotics and chemotherapeutics}; Triolo L; Antibiotics are of the greatest utility for the patient, but are sometimes troubling for the physician . The Author, from a standpoint different from that of the pharmacologist, speak about the many things that should be kept in mind whenever a treatment with such drugs must to be performed . Only so a therapy can be safe and effective. . The Author suggest a syndromic approach to recognize which is the causative agent of the current disease, and of consequence, which is the drug of choice . Antibiotics and chemiotherapeutic agents are briefly examined in their usefulness, limitations and side-effect . The new drugs, not yet available in Italy, are cited.

Biokhimiia, 1976 Dec, 41(12), 2183 - 90
{Effects of polyene antibiotics on the membranes of dog kidney isolated nuclei}; Asinobskaia NK et al.; The effects of amphotericin B and nistatin on the membranes of dog kidney isolated nuclei after their incubation with the antibiotics in question, have been studied . It is found that the polyene antibiotics, though they are superficially-active compounds, have no solubilizing effect on nuclear membranes and do not change their chemical composition . Electrophoretic study has revealed that nuclear membrane proteins, besides high- and low-molecular protein components, also contain a large amount of histones . The incubation of the nuclei with the polyene antibiotics results in marked changes in the fractional composition of nuclear membrane proteins, the most significant changes being induced by amphotericin B . It is assumed that polyene antibiotics induce proteolytic degradation of nuclear membrane proteins.

Antibiotiki, 1976 Dec, 21(12), 1106 - 13
{Comparative study of the cardiotoxicity of the anthracycline antibiotics, carminomycin and adriamycin, in white mice}; Gol'dberg LE et al.; The cardiotoxic effect of karminomycin and adriamycin administered intravenously for 5 times in equitoxic doses constituting equal portions of LD50 of the respective antibiotic on its single intravenous administration was studied on albino mice . Histological examination of the heart showed that almost identical damages of the myocardium occured after administration of karminomycin and adriamycin in doses of 0.45 of LD50 (1.5 mg/kg) and 0.3 of LD50 (6.3 mg/kg) respectively . The character of the damages due to the antibiotics was close, the most significant changes were observed when the animals were sacrificed 1 month after the last administration of the drug . The histological method is of value in estimation of the cardiotoxic effect of the drugs, using mice as the model suitable for the investigation . Adriamycin had more pronounced cumulative properties as compared to karminomycin: suppression of the weight gain in the mice and their death rate were higher with the use of adriamycin.

Carbohydr Res, 1976 Dec, 52, 187 - 96
Chemical modification of aminocyclitol antibiotics; Suami T et al.; The aminocyclitol antibiotic neamine has been chemically modified at the hydroxyl group on C-6 of the 2-deoxystrepatamine moiety . The partially acetylated neamine derivatives, 6,3,4-tri-O-acetyl- (3) and 5,3-57,4-tri-O-acetyl-1,3,2,6-tetra-N-(ethoxycarbonyl)neamine (4), were prepared by random hydrolysis of the 5,6-O-ethoxyethylidene derivative (2), followed by chromatographic purification . Condensation of 4 and 2,3,5-tri-O-benzoyl-D-ribofuranosyl chloride led to 6-O-(beta-D-ribonfuranosyl)neamine (7) . Analogous condensation of 4 with 2,3,4,6-tetra-O-acetyl-alpha-D-glucopyranosyl bromide or 2,3,4,6-tetra-O-acetyl-alpha-D-galactopyranosyl bromide afforded the corresponding 6-O-(D-hexopyranosyl)neamines.

Acta Pathol Microbiol Scand {B}, 1976 Dec, 84B(6), 369 - 72
Effect of antibiotics on interferon production in mice; Rollag H Jr et al.; Neomycin, chloramphenicol, gentamycin, rifampicin and oxytetracycline were tested for their influence on virus induced interferon (IF) production in mice . Repeated intraperitoneal (i.p.) injections of antibiotics were given to produce significant serum concentrations during the time of IF production, induced by i.p . injections of Newcastle disease virus (NDV) . IF titres in antibiotic-treated mice determined 6 hours after induction were compared to titres in control mice given NDV only . The IF production was not significantly modified in most of the antibiotic treated mice . Only the highest dose of chloramphenicol (2500 mug/mouse) appeared to cause a reduction in IF production (p less than 0.10) . Addition of antibiotics in vitro did not alter the antiviral titres of IF.

J Natl Cancer Inst, 1976 Dec, 57(6), 1249 - 52
Effect of antibiotics on mice treated with cyclophosphamide; Bruckner HW; The toxicity and therapeutic index of cyclophosphamide (CP) in NIH Wwiss and (C57BL X DBA)F mice were affected by the addition of different antibiotics to the drinking water . Penicillin G or Vancomycin increased the rat and number of deaths that followed parenteral treatment with CP; however, penicillin or Vancomycin alone produced no deaths . Both penicillin and Vancomycin changed the normal composition of the gastrointestinal bacteria, thus increasing the antibiotic-resistant coliform bacteria . Neomycin or gentamycin, with or without penicillin or Vancomycin, reduced the number of deaths that followed parenteral treatment with doses of CP lethal to 35% of the animals (LD35) . Neomycin and gentamycin reduced the number of coliform bacteria recoverable from the gastrointestinal tract . The doses of CP against L1210 murine leukemia . The combination of CP (LD35) with the aminoglycosides produced several long-term survivors, apparently because larger doses of CP can be used with few drug-related deaths.

J Nutr, 1976 Dec, 106(12), 1737 - 46
Effect of antibiotics on growth of the immature rat; Chawla RK et al.; The purpose of this study was to quantify the growth promoting effect of a mixture of antibiotics for rats eating diets deficient in protein or an essential amino acid . Male albino weanling rats (70 to 80 g weight, 4 weeks old) were fed (a) a control diet containing all other required nutrients and varying amounts of casein (0 to 27%), or (b) a purified amino acid diet containing all other required nutrients and varying amounts of valine (0 to 70 mumoles/g diet), threonine (0 to 69 mumoles/g diet) or tryptophan (0 to 8.6 mumoles/g diet), with and without an oral antibiotic supplement consisting of neomycin sulfate (10 mg/100 g body weight/day), bacitracin (500 units/100 g body weight/day), and polymyxin B sulfate (1 mg/100 g body weight/day) . At suboptimal intake of casein, valine, tryptophan or threonine, rats eating antibiotic-enriched diet showed up to 3 times greater daily body weight gain (deltaBW) than rats eating a similar diet without antibiotics . The growth-promoting effect of antibiotics can be expressed as percent sparing of specified nutrient (casein or individual amino acid), defined as below: (see journal) where nutrient intakeO ab or nutrient intakeab represents that intake of casein or of a particular amino acid which is required to produce a specific deltaBW in antibiotic-free or antibiotic-supplemented group, respectively . The percent sparing was inversely proportional to the dietary content of casein or limiting amino acid . For diets containing 10% to 25%, 25% to 50%, 50% to 75%, and 75% to 100% of the daily requirement of the limiting nitrogenous nutrient, sparing on the average was greater than 80%, 60%, 20%, and less than 10%, respectively . Data on daily food intake of ad libitum fed rats, and data from an experiment with tube-fed rats, showed that the growth-enhancing effect of antibiotics was independent of changes in food intake.

J Dairy Sci, 1976 Dec, 59(12), 2130 - 3
Survival and fertility of antibiotic-treated bovine spermatozoa; Berndtson WE et al.; Motility of spermatozoa stored at 5 C with up to 1000 units or mug of chloramphenicol, polymyxin, kanamycin, tylosin, ampicillin, lincomycin, spectinomycin, erythromycin, novabiocin, or terramycin per ml of extender was compared to that with penicillin plus dihydrostreptomycin . Novabiocin and terramycin were toxic, but other antibiotic treatments had no effect . However, erythromycin and tylosin, as well as colymycin, depressed motility of frozen thawed spermatozoa . Spermatozoal motility was equivalent, following freezing in ampules or straws . All of the antibiotics which were non-toxic when added singly to frozen semen were also not harmful to frozen spermatozoa when as much as 2000 units or mug were added per ml of extender containing penicillin and dihydrostreptomycin . The addition of 1000 units or mug of ampicillin, chloramphenicol, kanamycin, lincomycin, polymyxin, or spectinomycin per ml of extender containing 750 units penicillin and 750 mug dihydrostreptomycin per ml did not influence the fertility of frozen spermatozoa in a field test involving 19,663 first inseminations.

Arch Ophthalmol, 1976 Dec, 94(12), 2109 - 11
A continuous-wear hydrophilic lens . Prophylactic topical antibiotics; Binder PS et al.; Seventeen patients, who were fitted with a continuous-wear hydrophilic lens for 12 weeks, received topical neomycin sulfate-polymyxin B sulfate-gramicidin (Neosporin) eyedrops in one eye only at a frequency of 3.7 times per day . The continuous wear of a hydrophilic lens in and of itself did not after normal bacterial flora, and the use of the antibiotic drops did not alter normal conjunctival flora . In addition, the eyedrops were not more effective when used in conjunction with the hydrophilic lens and did not appear to produce resistant organisms during the 12-week study . In normal eyes, a continuously worn hydrophilic soft contact lens that is well tolerated does not adversely affect the bacterial flora and the addition of neomycin sulfate-polymixin B-gramicidin drops at a frequency of 3.7 times per day does not appear to be beneficial or necessary.

Fortschr Med, 1976 Nov 18, 94(33), 1957 - 61
{Behavior of exocrine pancreatic function during treatment with antibiotics and antineoplastic agents}; Fleischer K; The thesis is composed of two parts, the first part is concerned with experiments in rats, the second part confirms the findings in human beings . After administration of oxytetracycline, chloramphenicol and cyclophosphamide, respectively, to rats an approximately dose-dependent decrease in the pancreatic secretion of proteins and enzyme activities was demonstrable in vivo under exogenous stimulation . The exocrine pancreatic function was studied in humans by performing a secretin-pancreocymin test before and after treatment with oxytetracycline or chloramphenicol and before and after massive-dose therapy with cyclophosphamide or combined cytotoxic treatment (as outlined by De Vita) . The investigations further included an examination of the exocrine pancreatic function in subjects on maintenance therapy with cyclophosphamide or busulfan and a comparison with the exocrine pancreatic function in a group of controls . In the oxytetracycline-treated humans there was a depression of the amylase and lipase activities in the duodenal secretion . Administration of chloramphenicol produced a decrease in the amylase output only . In the patients on massive-dose or continued therapy with cyclophosphamide the pancreatic function remained essentially unchanged . In contrast, cytotoxic combination treatment resulted in decreased activities of amylase and lipase . After maintenance treatment with busulfan a reduction of the trypsin and amylase activities was detectable . The volume and electrolyte outputs were found to remain essentially unchanged in all investigations . An impairment in enzyme synthesis is suggested as the major cause of the observed changes of pancreatic secretion after antibiotic and cytotoxic treatment.

Biochem J, 1976 Nov 15, 160(2), 137 - 45
Competition between trichodermin and several other sesquiterpene antibiotics for binding to their receptor site(s) on eukaryotic ribosomes; Cannon M et al.; 1 . Of the five sesquiterpene antibiotics tested and found to inhibit protein synthesis in yeast spheroplasts, trichothecin, trichodermol or trichodermin stabilized polyribosomes whereas, in contrast, verrucarin A or T-2 toxin induced 'run off' of polyribosomes with a corresponding increase in 80S monoribosomes . The effect of fusarenon X on the system could not be determined as the drug failed to enter the cells . 2 . {acetyl-14C}Trichodermin bound to yeast polyribosomes with a dissociation constant of 2.10 muM and to yeast 'run off' ribosomes with a dissociation constant of 0.72 muM . 3 . Trichothecin, trichodermol, fusarenon X, T-2 toxin and verrucarin A competed with {acetyl-14C}trichodermin for binding to its receptor site on 'run off' ribosomes . The observed competition was quantitatively similar for all drugs tested . In contrast, the five drugs competed to different extents with trichodermin for binding to its receptor site on polyribosomes . Thus trichothecin competed with relative efficiency, whereas verrucarin A competed poorly, and the other drugs occupied intermediate positions between these two extremes . 4 . Studies were also carried out with yeast 'run off' ribosomes prepared from both a wild-type strain and a strain resistant to trichodermin . Competition experiments between verrucarin A and {3H}anisomycin indicated that verrucarin A bound to 'run off' ribosomes from the mutant strain less efficiently than to those from the wild-type.

Antibiotiki, 1976 Nov, 21(11), 1005 - 7
{Antitumor activity of carminomycin antibiotic used orally}; Shorin VA et al.; Antitumor activity of karminomycin used perorally was studied with respect to 3 strains of mouse transplantable tumors, i . e . one ascitic strain of lymphadenosis NK/LI and two solid strains of lymphosarcoma L10-1 and sarcoma 180 . Karminomycin was shown to have a high antitumor activity against the above tumors on its oral administration . In the experiments with lymphadenosis NK/LI the efficiency of karminomycin was higher when it was used perorally as compared to its intravenous administration . It was found that karminomycin had practically the same inhibitory effect on growth of lymphosarcoma L10-1 and sarcoma 180 on its peroral and intravenous administration in doses equivalent by their toxicity.

Probl Endokrinol (Mosk), 1976 Nov-Dec, 22(6), 106 - 10
{Effect of certain antibiotics of tetracycline series on the level of blood sugar and the role of insulin in the mechanism of its regulation}; Storozhuk PG et al.; Experiments on male rats showed enterally administered tetracycline and chlortetracycline to promote an elevation of the blood sugar level . These antibiotics administered once together with glucose retarded the normalization of the blood sugar concentration . After 7-day administration of tetracycline and chlortetracycline glucose load caused a stable hyperglycemia . Special experiments with depancreatization and insulin injection to the animals and also the intravenous injection of glucose and the antibiotic demonstrated that the changes in the blood sugar concentration under the effect of tetracycline were associated both with its inhibitory action on the absorbing function of the intestine and with the retarded glucose utilization in the tissues . Insulin injected intramuscularly eliminated the hyperglycemic effect caused by the antibiotics.

Poult Sci, 1976 Nov, 55(6), 2142 - 7
Variable rachitogenic effects of grain and alleviation by extraction or supplementation with vitamin D, fat and antibiotics; MacAuliffe T et al.; Three experiments were conducted using day-old broiler type chicks to determine the effect of different cereal grains on vitamin D3 utilization and to investigate the effects of rye, corn, wheat and triticale as the cereal grain component of the diets on the development of a rachitic condition in chicks . Rye was submitted to acid treatment and water extraction in an attempt to destroy or isolate the rachitogenic factor . Results showed that with chicks fed a diet containing 200 I.U . of vitamin D3 with corn as the grain, mineralization of their bones was normal . Growth and bone ash were depressed when rye replaced corn in the diet . These effects were partially reversed when either fat or procaine penicillin was added to the diet, and comppletely prevented with a high level of vitamin D3 (2,000 I.U./kg.) . In another experiment, triticale depressed bone ash even though it did not affect body growth to the same extent as rye . Our results indicate that the factor responsible for the rachitogenic condition of rye-fed chicks can be removed by water extraction of this grain or partially destroyed by acid autoclaved treatment . A combination of acid autoclaved treatment and penicillin supplementation prevented the depression in bone ash.

J Biomed Mater Res, 1976 Nov, 10(6), 929 - 38
Mechanical properties of bone cements containing large doses of antibiotic powders; Lautenschlager EP et al.; The addition of up to 10 g gentamicin sulfate antibiotic powder to 60 g units of Simplex-P acrylic bone cement caused gradual, proportional decreases in the bulk muchanical properties of compressive and diametral tensile strengths . Water leaching of the antibiotic from the cement did not significnatly decrease these strenghts . Scanning electron microscopy (SEM) and energy-dispersive x-ray spectroscopy (EDS) showed the antibiotic to reside in the acrylic matrix as discrete particles not usually associated with internal porosity . The surface-sensitive flexural strength of a proprietary bone cement was lowered immediately by small quantities of antibiotic powder, and continued to decrease as doses of up to 10 g/unit were admixed . Water leaching caused channeling as the antibiotic was removed from the surface, but it did not create further changes in flexural strength.

J Biomed Mater Res, 1976 Nov, 10(6), 837 - 45
Mechanical strength of acrylic bone cements impregnated with antibiotics; Lautenschlager EP et al.; Admixing of several antibiotic powders which were insoluble in methyl methacrylate did not decrease the compressive and diametral tensile strengths of two acrylic bone cements when tested after setting for 1 day and after leaching 40 days in water at 37 degrees C . When antibiotics were added as water solutions, the included water resulted in a significant decrease in these bulk mechanical properties . Storage in water for 40 days caused surface irregularities only on specimens of the set antibiotic admixtures . Approximately 0.5% of the admixed dosage of these water-soluble antibiotics could be leached from the set cements . The observed surface channels, presumably left by the loss of antibiotic, suggest further study of surface-sensitive mechanical properties may be needed . The bulk mechanical strengths presented here are conclusive only for the particular combinations of antibiotics and cements investigated, and should not be generalized at this time to any or all antibiotic admixtures or other mechanical properties.

J Antibiot (Tokyo), 1976 Nov, 29(11), 1171 - 81
Studies on juvenimicin, a new antibiotic . II . Isolation, chemical characterization and structures; Kishi T et al.; A series of new macrolide antibiotics was isolated from the culture filtrate of Micromonospora chalcea var, izumensis . The fat-soluble basic complex consisted of eight components which were named juvenimicin A1 approximately A4 and B1 approximately B4 . Juvenimicin A3 was found to be identical with rosamicin and the structures of four of the other components (JVM A2, A4, B1 and B3) have been elucidated . Juvenimicin A2 has a methyl group at position 6 instead of the formylmethyl group of juvenimicin A3 . Juvenimicin A4, B1 and B3 possess a hydroxyethyl group at position 6 . Juvenimicin A4 and B1 differ from each other in the nature of the chromophore . Juvenimicin B3 differs from juvenimicin B1 in that a hydroxymethyl group is present at position 14 in the former.

J Antibiot (Tokyo), 1976 Nov, 29(11), 1152 - 62
Sorbistin, a new aminoglycoside antibiotic complex of bacterial origin . III . Structure determination; Konishi M et al.; The structures of sorbistins A1, A2, B, C and D have been determined including stereo-chemistry . Sorbistins A1, A2 and B are composed of a 4-acyl-amino-4-deoxy-D-glucose and 1,4-diamino-1,4-dideoxy-D-sorbitol, the latter compound being hitherto undescribed in literature . Sorbistins C and D have the same aglycone of 1,4-diamino-1,4-dideoxy-D-sorbitol, which is linked with D-glucose and 4-amino-4-deoxy-D-glucose, respectively, through a glycosidic bond.

Hum Pathol, 1976 Nov, 7(6), 693 - 703
Pseudomembranous colitis associated with antibiotics; Medline A et al.; Colitis associated with antibiotics, particularly with lincomycin and clindamycin, is a well established entity . The colitis may be clinically and radiologically very difficult to distinguish from inflammatory bowel disease, including Crohn's disease and ulcerative colitis . A wide spectrum of pathological features is described with various antibiotics . However, the pathological picture in the pseudomembranous form is quite distinctive . The most important histological findings include a "mushroom-like" or "explosive" appearance of the pseudomembrane with a sudden transition to normal mucosa adjacent to the lesion . Rectal biopsy is both an accurate and a rapid method of establishing the diagnosis.

Clin Orthop, 1976 Nov-Dec, (121), 67 - 73
The effect of high pressure insertion and antibiotic inclusions upon the mechanical properties of polymethylmethacrylate; Weinstein AM et al.; The properties of self-curing polymethylmethacrylate as affected by the admixing of an antibiotic to the powder-liquid mixture and as affected by insertion technique demonstrated that the antibiotic agent may leach from the surface of the acrylic, but not necessarily from the interior . The compressive and tensile strength, determined on two different commercial formulations, suggests that the antibiotic additive is not detrimental to the mechanical properties . A high pressure insertion technique produces a significant improvement in the mechanical properties of the self-curing acrylic material.

Biophys J, 1976 Nov, 16(11), 1297 - 314
The interaction of the polyene antibiotic lucensomycin with cholesterol in erythrocyte membranes and in model systems . III . Characterization of spectral parameters; Strom R et al.; The variations of optical density and fluorescence of lucensomycin are good indices of the binding of this polyenic antibiotic to membranes . The former parameter reflects more generally the binding to any site present in the membrane, while the latter is more specific for binding to cholesterol . The chromophore of the lucensomycin-cholesterol complex has a relatively long lifetime, is almost immobile in the membrane, and is not accessible to water-soluble fluorescence-quenching agents . The stoichiometry, evaluated fluorometrically, corresponds to about two cholesterol molecules per polyene . In colloidal cholesterol suspensions, the extent of binding as a function of free polyene concentration is described by rectangular hyperbolae, the dissociation constant being, however, dependent on the sterol concentration . In erythrocyte membranes, on the other hand, and even more markedly in model systems containing appropriate solvents, the combination between lucensomycin and the sterol sites is described by sigmoid titration curves, indicative of cooperative effects, and probably due to solvation of cholesterol.

Res Vet Sci, 1976 Nov, 21(3), 361 - 3
Comparison of two methods for detecting antibiotic residues in slaughter animals; McCracken A et al.; A comparison was made of the sensitivity of two methods in current use for the detection of antibiotic residues in slaughter animals . Calves previously given therapeutic injections of an antibiotic were used and a variety of samples were tested.

Antibiotiki, 1976 Nov, 21(11), 1026 - 30
{Preliminary results of a cooperative clinical study of the new antitumor antibiotic, carminomycin}; Borisov VI et al.; The clinical trials of karminomycin, a new Soviet antitumor antibiotic in treatment of different malignant tumors showed that the drug had a pronounced antitumor activity against the soft tissue sarcomas of various histogenesis, lympho- and reticulosarcoma, acute leukemia and some other neoplasms.

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