FEBS Lett, 1984 May 21, 170(2), 268 - 72 The effect of lipopolysaccharide on lipid bilayer permeability of beta-lactam antibiotics; Hiruma R et al.; The lipid-bilayer permeability of cephalosporins was extensively suppressed by addition of lipopolysaccharide to liposomal membrane in proportion to the hydrophobicity of the drugs . This suggests that the polysaccharide chain layer contributes to the barrier function . The importance of the polysaccharide chain in the barrier function was also supported by the fact that the permeability to Rd-type lipopolysaccharide-containing liposomes showed essentially the same dependency on the hydrophobicity of the cephalosporins as that of the lipopolysaccharide-free liposomes . In this case the permeability of the cephalosporins was proportional to their hydrophobicity . Similar lipopolysaccharide effect was also observed in the permeation of penicillins. Lancet, 1984 May 19, 1(8386), 1113 - 4 Sodium content of injectable beta-lactam antibiotics; Baron DN et al.; Many users of antibiotics are unaware of their ionic content . The ionic content is a particularly important factor for injectable beta-lactam compounds in patients on a restricted sodium intake . A table of the sodium content of commonly prescribed beta-lactam compounds is provided. Antibiotiki, 1984 May, 29(5), 378 - 82 {Criteria for evaluating the severity of peritonitis and the effectiveness of antibiotic therapy}; Stashchuk VF et al.; The possibility of objective estimation of the peritonitis severity by the nose skin autoflora, leucocytic intoxication index (LII) and central lymph toxicity was studied on 25 dogs . The forearm skin autoflora, LII and central lymph toxicity were estimated clinically in 86 patients . The advantage of the endolymphatic therapy with kanamycin over its intramuscular injection was shown. J Antibiot (Tokyo), 1984 May, 37(5), 475 - 8 Terrecyclic acid A, a new antibiotic from Aspergillus terreus . III . 13C NMR spectrum of terrecyclic acid A; Hirota A et al.; Assignment of the fifteen carbons of terrecyclic acid A, C15H20O3, a new sesquiterpene antibiotic, in the 13C NMR spectrum was performed by 13C-{1H} selective proton decoupling experiments, comparison with spectra of its derivatives and chemical shifts. Gastroenterol Clin Biol, 1984 May, 8(5), 426 - 9 {Diffuse recto-colic malacoplakia: association with cryptogenic colitis and remission following long-term antibiotic therapy}; Le Bourgeois P et al.; Diffuse digestive malakoplakia appears exceptional . A case of rectocolic malakoplakia with multiple localisations is reported in a 22 year old man presenting with inflammatory bowel disease . The most prominent clinical features were deterioration of his general condition, fever, and rectal bleeding, with fistula . Endoscopy revealed pseudotumoral masses and multiple colorectal ulcerations . Diagnosis was based on histological examination of colorectal biopsies . Clinical and histological remission was obtained after colonic diversion associated with broad spectrum antibiotherapy . These findings raise the problem of the possible association between inflammatory bowel disease and malakoplakia . They also confirm that, as previously reported, favourable outcome in digestive malakoplakia is possible. Plast Reconstr Surg, 1984 May, 73(5), 811 - 7 An experimental model to determine the level of antibiotics in irradiated tissues; Cruz NI et al.; An experimental study was designed using male Sprague-Dawley rats treated with a single dose of 1800 rads to an area of skin and soft tissue of the back measuring 2 X 3 cm . This dose was estimated to produce changes equivalent to 6000 rads in divided doses over 6 weeks . At intervals of 5, 10, and 15 weeks after irradiation, punch biopsies were taken from both irradiation, and nonirradiated skin areas of each animal 30 minutes after the intraperitoneal administration of gentamicin . Skin homogenates were prepared, and the antibiotic levels in these samples were determined by a bacterial growth inhibition assay . The antibiotic levels were found to be equal (16.1 +/- 6 micrograms/ml vs . 16.0 +/- 5 micrograms/ml) in both irradiated and nonirradiated skin at 5 weeks after radiation . However, at 10 and 15 weeks after radiation, the antibiotic levels had dropped to 9.9 +/- 3 micrograms/ml in irradiated skin compared with 14.1 +/- 4 micrograms/ml in normal skin (p less than 0.001) and with 5.4 micrograms/ml in irradiated skin vs . 11.8 +/- 5 micrograms/ml in nonirradiated skin (p less than 0.001), respectively . Results demonstrate that in spite of adequate gentamicin levels in the circulation and nonirradiated tissue in rats, gentamicin has a decreasing ability to diffuse into irradiated tissues with increasing intervals after therapeutic doses of radiation. Laryngoscope, 1984 May, 94(5 Pt 1), 612 - 4 One day vs . two days of prophylactic antibiotics in patients undergoing major head and neck surgery; Fee WE Jr et al.; Thirty patients undergoing major head and neck surgery were prospectively randomized to receive moxalactam (30 mg/kg) before surgery and for either 3 or 6 doses total postoperatively . Wound infection criteria were carefully specified and serum drug levels were monitored . Overall infection rate was 3%; the single infection occurred in a patient randomized to the 3 dose protocol . There was no statistically significant difference in infection rates between the two groups . Drug serum levels between the groups did not differ and none of the patients developed significant drug side effects . We conclude that short course prophylaxis is equally effective as more prolonged therapy . Our wound infection rate compares favorably with previous studies and supports the use of moxalactam as a prophylactive antibiotic in major head and neck surgery. J Cell Physiol, 1984 May, 119(2), 198 - 203 Chinese hamster ovary cell variants resistant to monensin, an ionophoric antibiotic . I . Isolation and altered endocytosis of ricin; Ono M et al.; Chinese hamster ovary (CHO) cell variants resistant to a carboxylic ionophore, monensin, have been isolated . Two monensin-resistant variants (MonR-31 and MonR-32) showed a three- to fourfold higher resistance to monensin than did CHO . These MonR clones also showed fourfold higher resistance to another carboxylic ionophore, nigericin, and twofold higher resistance to valinomycin . They were also slightly more resistant to other unrelated drugs such as adriamycin, colchicine, bleomycin, and chloroquine, and in particular, they showed about threefold higher resistance to ricin, a toxin of Ricinus communis . MonR clones were found to retain a normal level of {125I}ricin binding, but internalization of {125I}ricin into the MonR clones was one-half or less than with CHO . Present data suggest that drug-resistant clones selected in culture may provide a way to isolate cells with altered response to various bioactive molecules. Poult Sci, 1984 May, 63(5), 1027 - 32 Broiler chick growth response to antibiotics, 1981-1982; Dafwang II et al.; A study of the growth-promoting effects of penicillin, oxytetracycline, lincomycin, bambermycin , and tylan was made over a 2-year period involving 2030 broiler chicks in 11 experiments . The laboratory used for this study has been subjected to the continuous use of low level dietary antibiotics for over 30 years . Results show that growth promotion by penicillin, oxytetracycline, and lincomycin were still significant (P less than .01) . The effect of tylan was also significant (P less than .05) . The antibiotics tended to promote better growth effects in chicks from young breeder hens . Significant growth improvement by antibiotics was observed in nutritionally adequate diets regardless of the presence or absence of soybean meal and excesses of certain vitamins and minerals. Proc Natl Acad Sci U S A, 1984 May, 81(9), 2893 - 7 Mechanism of the inhibition of the gamma-carboxylation of glutamic acid by N-methylthiotetrazole-containing antibiotics; Lipsky JJ; Antibiotics that contain a 1-N-methyl-5-thiotetrazole (MTT) side group have been associated with hypoprothrombinemia . In a detergent-treated rat liver microsomal system, MTT inhibited the carboxylation of the gamma carbon of glutamic acid, a necessary reaction in the synthesis of four of the clotting factors . In the present work, the inhibition by MTT was found to be slow in onset, with a lag time of 15 min before significant inhibition occurred . A preincubation of MTT with the microsomes decreased the lag time and increased the extent of inhibition . Glutathione at 1 mM was found to markedly decrease the ability of MTT to inhibit this reaction . The disulfide dimer of MTT was a more potent inhibitor of the system than was MTT, with inhibition detected as low as 1 microM dimer . Disulfiram also inhibited the carboxylation system . These results indicate that the sulfhydryl group of MTT is important for the inhibitory effect of MTT and suggest that a slowly formed metabolite of MTT may be directly responsible for the observed inhibition . The inhibitory mechanism of MTT may be analogous to that of disulfiram, which would explain some pharmacologic effects in common with disulfiram . In addition, the in vitro observations presented here and a closer examination of the clinical evidence raise the possibility that MTT-containing antibiotic-induced hypoprothrombinemia may not be a vitamin K reversible phenomenon. Cancer Res, 1984 May, 44(5), 1928 - 32 Anticancer activity of the structurally novel antibiotic Cl-920 and its analogues; Leopold WR et al.; Cl-920 is a structurally novel phosphate ester antibiotic that contains an unsaturated lactone and a conjugated triene system . It has potent antileukemic activity in mice . At doses of 25 mg/kg given i.p . once daily for 5 days to mice bearing approximately 10(7) L1210 leukemia cells, Cl-920 is curative in about 10% of the mice . Life span increases in noncured mice are typically in excess of 150% . The unsaturated lactone and phosphate ester moieties are required for activity against L1210 leukemia . Ring hydroxylation or removal of the terminal hydroxyl group have only modest effects on activity . Schedule studies suggest that prolonged exposure to low levels of Cl-920 is considerably more toxic than is daily or intermittent administration . Daily administration produces optimal activity against L1210 leukemia . Administration i.p . and i.v . of Cl-920 produce roughly equal toxicity and equal activity against an i.p . implant of L1210 leukemia . Cl-920 is inactive when given p.o . or s.c . Cl-920 failed to show confirmed activity against the following tumors in mice: M5076 sarcoma, B16 melanoma, and Ridgway osteogenic sarcoma . The lack of solid tumor activity in mice may be caused by a transport deficiency similar to that found with methotrexate. J Antibiot (Tokyo), 1984 May, 37(5), 454 - 61 Stigmatellin, a new antibiotic from Stigmatella aurantiaca (Myxobacterales) . I . Production, physico-chemical and biological properties; Kunze B et al.; An antibiotic activity was extracted from the cell mass of the myxobacterium, Stigmatella aurantiaca strain Sg a15 . The antibiotic was toxic for yeasts and filamentous fungi, but not for most bacteria . The compound had the molecular formula C30H42O7, appears to be a new antibiotic, and was named stigmatellin . In addition to stigmatellin, the strain produced relatively large quantities of a second, structurally unrelated antibiotic, a mixture of three myxalamid homologues. Biochimie, 1984 May, 66(5), 333 - 52 Daunorubicin and doxorubicin, anthracycline antibiotics, a physicochemical and biological review; Aubel-Sadron G et al.; Daunorubicin and doxorubicin, two antibiotics belonging to the anthracycline group, are widely used in human cancer chemotherapy . Their activity has been attributed mainly to their intercalation between the base pairs of native DNA . Complex formation between daunorubicin or doxorubicin with polydeoxyribonucleotides and DNAs of various base composition or chromatins has been investigated by numerous techniques . Many authors have tried to correlate biological and therapeutic activities with the affinity of the drugs for DNA or some specific sequences of DNA . In vivo these anthracycline drugs cause DNA damage such as fragmentation and single-strand breaks . The mechanism of action of anthracyclines involves the inhibition of RNA and DNA syntheses . There exists two limiting factors in the use of anthracyclines as antitumoral agents: a chronic or acute cardiotoxicity and a spontaneous or acquired resistance . In both cases, there is probably an action at the membrane level . It has to be noted that daunorubicin and doxorubicin have a particular affinity for phospholipids and that the development of resistance is linked to some membrane alterations. Appl Environ Microbiol, 1984 May, 47(5), 1164 - 6 Susceptibility of Saccharomyces spp . and Schwanniomyces spp . to the aminoglycoside antibiotic G418; Panchal CJ et al.; Industrially useful polyploid yeasts such as the brewing yeasts do not possess any auxotrophic genetic markers and hence are not easily amenable to plasmid-mediated DNA transformations . In an attempt to obtain genetic markers, a number of useful Saccharomyces sp . strains and some amylolytic Schwanniomyces sp . strains were tested for their susceptibility to the antibiotic Geneticin G418 , a 2-deoxystreptamine reported to be active against bacteria, yeasts, and plant and animal cells . All of the Saccharomyces sp . strains, including the brewing strains, were found to be susceptible to G418 in the concentration range of 150 to 500 micrograms/ml . Of the three Schwanniomyces species investigated, only Schwanniomyces castellii (strain 1402) was found to be resistant to G418 at concentrations up to 1 mg/ml . Resistance was exhibited both in liquid media and on glycerol-peptone-yeast extract agar plates . This finding is interesting in view of the possibility of using this strain as a DNA donor for transformations aimed at introducing the amylolytic capability into brewing yeasts. J Antibiot (Tokyo), 1984 May, 37(5), 596 - 601 Bacterial uptake of habekacin, a novel aminoglycoside antibiotic; Matsunaga K et al.; Cellular uptake of habekacin, 1-N-(4-amino-2-hydroxybutyryl)dibekacin, was studied by incubating exponentially growing culture of Escherichia coli Q13 and its kanamycin-resistant mutants with {3H}habekacin . Kanamycin-resistant mutants, in which the resistance is due to alteration of ribosomes, were cross-resistant to habekacin, and showed a lower uptake of {3H}habekacin than the parental cells, suggesting that binding to ribosomes accelerates cellular uptake of habekacin . Cellular accumulation of {3H}habekacin by wild type cells was markedly inhibited by low temperature and by 2,4-dinitrophenol, suggesting that uptake of habekacin involves energy-dependent transport . The uptake of {3H}habekacin was reduced by various aminoglycoside antibiotics, suggesting common transport systems and/or common internal binding sites on the ribosome . Intracellular accumulation of {3H}dibekacin was reduced by habekacin, suggesting that both antibiotics possess a common transport system and/or common binding sites on the ribosome . Dibekacin was a better competitor than amikacin, suggesting that the dibekacin moiety of habekacin molecule, but not the 4-amino-2-hydroxybutyryl moiety, participates in the transport and/or binding to the ribosome . Binding of {3H}habekacin to E . coli ribosomes was reversed by various aminoglycosides and the degree of inhibition paralleled the one of cellular uptake, suggesting that competition by aminoglycosides for the habekacin uptake occurs at the ribosomal level. J Cell Physiol, 1984 May, 119(2), 204 - 10 Chinese hamster ovary cell variants resistant to monensin, an ionophoric antibiotic . II . Growth requirement for insulin and altered insulin-receptor activity; Sato Y et al.; From the Chinese hamster ovary (CHO) cell, genetic variants (MonR-31 and MonR-32) relatively resistant to monensin, an ionophoric antibiotic, have been isolated . Growth of both MonR-31 and MonR-32 clones required higher doses of serum than CHO . Addition of insulin to media containing a low dose of serum restored full colony formation, but growth of MonR-31 or MonR-32 cells required more insulin than CHO cells . Specific binding of {125I}insulin was observed in these cell lines . The two MonR clones bound about one-half or less the {125I}insulin bound by CHO cells . Scatchard analysis for {125I}insulin binding at 4 degrees C and 37 degrees C showed altered number of binding sites, but not insulin affinity: The number of binding sites in the MonR cell was about a half or less that of the parental CHO cell . Down-regulation of insulin receptor was assayed when both CHO and MonR cells were incubated with 1 microgram/ml insulin . A 50-60% decrease in levels of insulin surface binding capacities was observed in CHO after exposure to insulin, whereas there was no decrease in MonR cell . The cellular uptake of 2-{3H}deoxyglucose into CHO cells was significantly enhanced in the presence of insulin, but only slight, if any, increase was observed in MonR cells. Pathol Biol (Paris), 1984 May, 32(5), 355 - 8 {Evaluation of the modulatory effects of in vivo antibiotics on phagocytosis in mice using various methods}; Gillissen G et al.; The influence of cefoxitin and cefotaxim on phagocytosis in vitro and intracellular microbicidal activity of peritoneal macrophages and granulocytes was examined . In addition, the influence of these antibiotics on the elimination rate of Candida was controlled 4 and 24 hours after intraperitoneal injection . The two antibiotics were shown to have no influence on phagocytosis of Candida . Microbicidal activity was inhibited only by cefoxitin . This result is consistent with the reduction of metabolic activity of phagocytes caused by cefoxitin but not cefotaxim, in vivo as well as in vitro . Both antibiotics induce a reduction of Candida cells recovered 4 hours after intraperitoneal injection . However, the effect of cefotaxim was significantly more pronounced than that of cefoxitin . 24 hours after infection, the result was comparable but the number of Candida cells recovered in the spleen was higher with cefoxitin than with cefotaxim . The clinical bearing of these results remains to be discussed. J Clin Microbiol, 1984 May, 19(5), 707 - 9 Measurement of levels of aminoglycosides and vancomycin in serum in the presence of new beta-lactam antibiotics; Calderwood SB et al.; We evaluated the effect of new beta-lactam antibiotics (azlocillin, mezlocillin, piperacillin, cefotaxime, moxalactam, and cefoperazone) on assays for aminoglycosides and vancomycin . These antibiotics produced no interference in an immunoassay for gentamicin and tobramycin . The new penicillins produced no interference in a bioassay of amikacin and vancomycin with penicillinase incorporated into the assay agar . Bioassay in the presence of the cephalosporins required predigestion with cephalosporinase . We describe a method for accurate bioassay in the presence of the available cephalosporins, with the exception of moxalactam. Drug Metab Dispos, 1984 May-Jun, 12(3), 365 - 70 The disposition of the new anthracycline antibiotic, menogarol, in mice; Dodion P et al.; We have investigated the metabolism and disposition, in mice, of 7-con-O-methylnogarol ( menogarol ; 7-OMEN), a new anthracycline antibiotic entering clinical trials . 7-OMEN, dissolved in 0.01 M glucuronic acid, was administered iv to mice (10 mg/kg) . At specified times after injection, groups of mice were killed and 7-OMEN and metabolites were assayed in plasma and organs by HPLC . Plasma concentrations of 7-OMEN declined in triexponential fashion . The terminal t1/2 was 10.6 hr; the AUC was 10.13 microM X hr; the apparent Vc was 0.4 liter/m2, and the systemic clearance was 91.2 ml/min/m2 . One metabolite, with the same HPLC characteristics as N- demethylmenogarol , was seen in plasma during the first 30 min after injection . 7-OMEN was distributed extensively to all tissues except brain . Initially, pulmonary concentrations of 7-OMEN were 15 times higher than those in any other organ and 30 times higher than those in plasma . Concentrations of 7-OMEN were the most persistent in spleen, kidney, and pancreas, and the least persistent in heart and liver . The AUC for 7-OMEN in organs was the greatest in lungs (605 nmol/g X hr), spleen (522 nmol/g X hr), and pancreas (430 nmol/g X hr), and least in heart (33 nmol/g X hr) and liver (60 nmol/g X hr) . Kidneys and skeletal muscles had intermediate AUC values . In liver, two metabolites, one of which had the HPLC characteristics of N- demethylmenogarol , were seen . In other organs, the same metabolites were seen later and in small quantities. No Shinkei Geka, 1984 May, 12(6), 681 - 6 {Concentration of antibiotics (cefoperazone) in human brain, brain tumor tissue and cerebrospinal fluid}; Ito H et al.; The transfer of cefoperazone (CPZ) into cerebrospinal fluid (CSF), brain or brain tumor tissue was studied in 13 cases with brain tumor, chronic subdural hematoma and benign intracranial hypertension in 1982 . The peak values of CPZ in serum came up immediately after its rapid intravenous administration and then decreased exponentially . The concentration of CPZ in CSF started to increase with a long delay of about 60 min . The average peak level in CSF remained 21.6 micrograms/ml and corresponded to 10.3% of the peak level in serum . The best transfer of chloramphenicol into CSF has been reported, while that of CPZ would be one of the next . The CPZ levels in CSF showed a slower decay than in serum . The concentration of CPZ in brain reached the peak level in less than 30 min and the average peak level was 36.5 micrograms/g cerebral tissue . The brain to blood rate of the CPZ concentration was 11.1% . The CPZ levels in the brain showed a rapid decrease like the transition of antibiotic levels in serum . The antibiotic levels in brain tumors were divided into two groups . The one showed sharp peak about one tenth of the values in serum . The other was of a slowly increasing type. Biochemistry, 1984 Apr 10, 23(8), 1668 - 74 Dissociation kinetics and equilibrium binding properties of polyene antibiotic complexes with phosphatidylcholine/sterol vesicles; Witzke NM et al.; The interactions of sonicated vesicles with the polyene antibiotics amphotericin B, candicidin, mediocidin , and a water-soluble, guanidine derivative of amphotericin B were examined by UV-visible spectroscopy at concentrations below which the polyenes become self-associated . The association constants, Kapp, and the numbers of binding sites per sterol or phospholipid molecule (n) were determined at 30 degrees C and pH 7.4 . A single class of binding sites was found, with no evidence of cooperativity . For the binding of mediocidin , amphotericin B, and the guanidine derivative with phosphatidylcholine (PC), PC/cholesterol, and PC/ergosterol vesicles, Kapp was in the range of (1.0-3.0) X 10(6) M-1; Kapp was higher for candicidin-vesicle interaction, reaching 9.0 X 10(6) M-1 with PC/ergosterol vesicles . Binding of the guanidine derivative of amphotericin B to PC vesicles lacking sterol was extensive (n = 0.46); since the other polyenes, which have low aqueous solubilities, had n less than 0.05, positive charges in the mycosamine moiety appear to enhance the extent of polyene antibiotic interaction with the glycerophospholipid head group . Higher values of n (and, therefore, of nKapp ) were found with sterol-containing than with sterol-free vesicles, suggestive of penetration of the polyenes toward the interior of the bilayer when sterol is present . For binding to PC/sterol vesicles, nKapp followed the order of candicidin greater than guanidine derivative of amphotericin B greater than amphotericin B much greater than mediocidin . The values of n and nKapp were appreciably higher for amphotericin B-ergosterol than for amphotericin B-cholesterol interaction in vesicles.(ABSTRACT TRUNCATED AT 250 WORDS) Eur J Pharmacol, 1984 Apr 6, 99(4), 303 - 11 The effects of locally injected antibiotic on carrageenan-induced granuloma in rats; De Maroussem D et al.; Indomethacin (0.5 mg/100 g b.w./day) and chloramphenicol (0.5 mg or 15 mg/100 g b.w./day) were tested for their anti-inflammatory effects on 7th day carrageenan-induced granuloma formation . Neither of the drugs modified granuloma or pouch wall weight but they decreased the exudate and the cluster of dead cells . Indomethacin and chloramphenicol decreased glucosamine in the dead cell granuloma fraction and increased the level of collagen in the pouch wall . The drugs differed in their inhibitory effect on lysozyme and prostaglandin E2 accumulation in the exudate . The increase in collagen was related to a drop in the level of prostaglandin E2 which seems to regulate collagen deposition in the granuloma . However, the prostaglandin E2-lysozyme correlation--which was only significant with chloramphenicol--suggests a mode of action for chloramphenicol different from that of indomethacin . Chloramphenicol could act by a myelodepressive and/or chemotactic effect . The effects of chloramphenicol on the macrophages are discussed. J Anim Sci, 1984 Apr, 58(4), 801 - 4 Effect of space allowance and antibiotic feeding on performance of nursery pigs . NCR-89 committee on confinement management of swine; Cleavage of the Arg1-Pro2 bond of bradykinin by a human lung peptidase: isolation et al.; An aminopeptidase P (EC 3.4.11.9) that cleaves the Arg1-Pro2 bond of bradykinin has been isolated for the first time from human lung and purified 473-fold . The enzyme also catalyzes the cleavage of arginine from des-{Arg9}-bradykinin and the hydrolysis of several X-proline dipeptides including L-arginyl-L-proline, L-leucyl-L-proline, and L-alanyl-L-proline . Purified enzyme was routinely assayed (after initial identification with des-{Arg9}-bradykinin) with L-leucyl-L-proline . The molecular weight, in nondenaturing buffers, is 188,000 +/- 8500 Da . The pH optimum was 8.0 with arginyl-proline, and was 6.8 with leucyl-proline . Chelating agents do not inactivate the enzyme, but rather only remove loosely bound cations that stimulate the enzyme . Manganese is the principal cation that stimulates the enzyme . The enzyme is inhibited by several beta-lactam antibiotics, cephalexin and oxacillin being the most effective of those tested . The antibiotic inhibition is time and temperature dependent, and it is not fully reversible by exhaustive dialysis of the antibiotic-treated enzyme. J Antimicrob Chemother, 1984 Apr, 13(4), 353 - 9 Comparative susceptibilities of penicillin-resistant pneumococci to co-trimoxazole, vancomycin, rifampicin and fourteen beta-lactam antibiotics; Linares J et al.; Eighty-four isolates of penicillin-resistant pneumococci were tested for susceptibility to vancomycin, rifampicin, cotrimoxazole, and 14 beta-lactam antibiotics by agar and microbroth dilution methods . Twenty-three were from adult patients with pneumococcal disease, 57 from nasopharingeal carriers (preschool children) and four were resistant South African isolates . For all isolates tested, imipenem (N-formimidoyl thienamycin), rifampicin, ceftriaxone and cefotaxime had the greatest activity ( MIC90 : 0 X 12, 0 X 25, 0 X 5 mg/l, respectively) . Cefoxitin and latamoxef were the least active of the drugs studied . The remaining beta-lactams tested had less activity than that of penicillin . All strains were inhibited by 1 mg/l of vancomycin and all but one were resistant to cotrimoxazole . The excellent in-vitro activities of the newer beta-lactam agents (ceftriaxone, cefotaxime and, particularly, imipenem ) and vancomycin against penicillin-resistant pneumococci offer a considerable promise for their use in the treatment of pneumococcal meningitis caused by these strains. J Antibiot (Tokyo), 1984 Apr, 37(4), 354 - 62 Studies on macrocyclic lactone antibiotics . VII . Structure of a phytotoxin "rhizoxin" produced by Rhizopus chinensis; Iwasaki S et al.; A new 16-membered macrolide designated as rhizoxin was isolated as a toxin produced by Rhizopus chinensis, the causal agent of rice seedling blight . The skeletal structure was determined by detailed NMR spectroscopic investigation of this compound and of its derivatives . Rhizoxin induced at a concentration of 10 ng/ml abnormal swelling of rice seedling roots, which is one of the characteristic symptoms of this disease . This compound also exhibited potent antifungal activity but little effect against bacteria. Br J Urol, 1984 Apr, 56(2), 217 - 9 Factors influencing recurrence of urethral strictures after endoscopic urethrotomy: the role of infection and peri-operative antibiotics; Pain JA et al.; One hundred patients who had undergone 162 urethrotomies were reviewed . Factors which influenced the outcome of the procedure are discussed . Peri-operative infection occurred in 38% of cases and significantly increased the recurrence rate unless the patients were treated with antibiotics. J Antibiot (Tokyo), 1984 Apr, 37(4), 389 - 93 Binding of 125I-labeled beta-lactam antibiotics to the penicillin binding proteins of Escherichia coli; Rojo F et al.; 125I-Labeled derivatives of the beta-lactam antibiotics cephalexin, cephradine, cefaclor and 6-alpha-aminopenicillanic acid have been obtained by reacting these compounds with (125I)-Bolton-Hunter reagent . The following target proteins were found in Escherichia coli: (1) The derivatives of cephalexin, cefaclor and cephradine preferentially interact with the high molecular weight penicillin binding proteins ( PBP1a and PBP1b ); (2) The 125I- derivative of 6-alpha-aminopenicillanic acid is preferentially bound by the low molecular weight penicillin binding proteins 4 and 5/6 . The iodinated derivatives showed a very high affinity of binding to their target proteins with apparent half-saturating concentrations in the nano -molar range. Diagn Microbiol Infect Dis, 1984 Apr, 2(2), 93 - 100 Comparative study of the ability of four aminoglycoside assay techniques to detect the inactivation of aminoglycosides by beta-lactam antibiotics; Pfaller MA et al.; In vitro inactivation of aminoglycosides (tobramycin, gentamicin, and amikacin) by beta-lactams (cefazolin, cefotaxime, moxalactam, carbenicillin, piperacillin, mezlocillin, and azlocillin) was measured using the enzyme-mediated immunoassay (EMIT), fluorescence polarization immunoassay ( TDX ), radioimmunoassay (RIA), and bioassay . No significant inactivation of aminoglycosides was produced by high levels of the three cephalosporins as measured by EMIT, RIA, or bioassay . Inactivation of tobramycin and gentamicin by mezlocillin and azlocillin was comparable to that seen with piperacillin but less than that with carbenicillin . In general, the bioassay detected the greatest degree of aminoglycoside inactivation and the EMIT assay detected the least for all drug combinations . The TDX and RIA techniques were equivalent in their ability to detect aminoglycoside inactivation by beta-lactam antibiotics. J Trauma, 1984 Apr, 24(4), 307 - 10 A prospective comparison of two regimens of prophylactic antibiotics in abdominal trauma: cefoxitin versus triple drug; Hofstetter SR et al.; To determine the best antibiotic regimen to employ in patients undergoing laparotomy for trauma, a randomized prospective study was designed comparing cefoxitin alone with a triple-drug regime of an aminoglycoside, ampicillin, and clindamycin . One hundred nineteen consecutive patients sustaining abdominal trauma (97 penetrating; 22 blunt) were divided by date of admission to a 24-hour course of antibiotics . The overall infection rate was 16.0%, with 14.5% of the cefoxitin-treated patients, and 18.0% of the triple-drug-treated patients developing an infectious complication . Excluding remote site infections, the abdominal wound and intraperitoneal infection rates were 13.0% for cefoxitin-treated patients, and 12.0% for triple-drug-treated patients . There was one instance of oliguric renal failure questionably related to an aminoglycoside . It is concluded that a 24-hour course of cefoxitin is a safe and effective prophylactic antibiotic regime in patients undergoing laparotomy for trauma. Exp Cell Res, 1984 Apr, 151(2), 299 - 305 Retention of mitochondrial DNA species in somatic cell hybrids using antibiotic selection; Solus JF et al.; Interspecific cell hybrids were constructed by fusion of an antimycin-resistant, thymidine kinase- (TK-) Chinese hamster cell line with a chloramphenicol-resistant, hypoxanthine-guanine phosphoribosyl transferase- (HPRT-) mouse cell line . Hybrids were selected in HAT medium alone, or HAT supplemented with chloramphenicol, antimycin, or both antibiotics . Analysis of the mitochondrial DNA (mtDNA) of these hybrids indicates that antibiotic selection directed at the mitochondrial populations results in retention of the resistant parental genome and loss of the sensitive parental genome. Can J Comp Med, 1984 Apr, 48(2), 171 - 4 The effect of antibiotics against bovine mycoplasmas and ureaplasmas; Truscott RB et al.; A combination of lincomycin-spectinomycin-tylosin was tested against several strains of mycoplasmas and acholeplasmas as might be encountered in bovine semen and shown to be effective against them . This combination as well as minocin , rosaramicin, rosoxacin, tiamulin, gentamicin and declomycin were tested in vitro against 58 isolates of ureaplasma from the bovine urogenital tract . The lincomycin-spectinomycin-tylosin combination, minocin , rosaramicin, tiamulin and declomycin were quite active, while rosoxacin and gentamicin were much less active against the test strains. Biochemistry, 1984 Mar 27, 23(7), 1462 - 7 Fidelity of the eukaryotic codon-anticodon interaction: interference by aminoglycoside antibiotics; Eustice DC et al.; A homologous in vitro method was developed from Tetrahymena for ribosomal A-site binding of aminoacyl-tRNA to poly(uridylic acid)-programmed ribosomes with very low error frequency . The reaction mixture pH was the crucial factor in the stable A-site association of aminoacyl-tRNA with high fidelity . At a pH greater than 7.1, endogenous activity translocated A-site-bound aminoacyl-tRNA to the P site . If translocation was allowed to occur, a near-cognate amino-acyl-tRNA, Leu-tRNA, could stably bind to the ribosome by translocation to the ribosomal P site . Near-cognate aminoacyl-tRNA did not stably bind to either site when translocation was blocked . Misreading antibiotics stimulated the stable association of near-cognate aminoacyl-tRNA to the ribosomal A site, thereby increasing the error frequency by several orders of magnitude . Ribosome binding of total aminoacyl-tRNA near equilibrium was not inhibited by misreading antibiotics; however, initial rate kinetics of the binding reaction were dramatically altered such that a 6-fold rate increase was observed with paromomycin or hygromycin B . The rate increase was evident with both cognate and near-cognate aminoacyl-tRNAs . Several antibiotics were tested for misreading potency by the ribosome binding method . We found gentamicin G418 greater than paromomycin greater than neomycin greater than hygromycin B greater than streptomycin in the potentiation of misreading . Tetracycline group antibiotics effectively inhibited A-site aminoacyl-tRNA binding without promoting misreading. Biochim Biophys Acta, 1984 Mar 22, 798(1), 111 - 4 A 15N nuclear magnetic resonance study of the biosynthesis of quinoxaline antibiotics; Reid DG et al.; Uniformly 15N-labelled triostin A and echinomycin have been prepared by growing the producing organisms on enriched media and their 15N nuclear magnetic resonance spectra partially assigned by a combination of nuclear Overhauser effect and scalar coupling constant measurements . Selective feeding experiments using unlabelled L-tryptophan-supplemented media have shown that N-1 and N-4 of the quinoxaline rings have their origins in the indole and amino groups of tryptophan, respectively. Antibiotiki, 1984 Mar, 29(3), 223 - 7 {Liver-protective effect of tocopherol acetate and selenium-containing preparations in tetracycline antibiotic lesions of the liver}; Skakun NP et al.; It was shown on 99 male albino rats that vitamin E, sodium selenite and Astragalus . L . infusion used separately lowered the toxic effect of tetracycline on the liver, while the use of vitamin E in combination with sodium selenite or Astragalus L . infusion prevented such an effect of the antibiotic . This was evident from the decreased levels of lipid peroxidation products, i.e . diene conjugates and malonic dialdehyde in the blood and liver, and a simultaneous increase in the ratio of sulfhydryl and disulfide groups in these biosubstrates . Parallelism of the changes in these indices of the blood and liver was observed . It is suggested that lipid peroxidation plays an important part in the pathogenesis of liver affection with tetracyclines . The combined use of vitamin E and selenium-containing drugs is considered advisable for the prophylaxis and treatment of such affections. Antibiotiki, 1984 Mar, 29(3), 170 - 5 {Retroaldol cleavage of the glyopeptide antibiotic ristomycin A during alkaline inactivation}; Trifonova ZhP et al.; The chemical and physicochemical characteristics of one of the two inactive components, i.e . the reduced product of alkaline inactivation (PAH-II) of ristomycin . A were studied . The components formed on the antibiotic incubation in mild alkaline media: 0.05 M NaOH, 37 degrees C, 1.5-2 hours . It was shown that the retroaldol cleavage of the C alpha-C beta bond of the phenol serine fragment of the trinuclear dideschlorvancomycinic acid G at the aglycone N-end was one of the causes of ristomycin A rapid inactivation under such conditions. J Reprod Med, 1984 Mar, 29(3), 173 - 8 Continual postoperative antibiotic peritoneal lavage in diffuse peritonitis complicating cesarean section; Rivlin ME et al.; Nine women treated surgically for diffuse peritonitis complicating cesarean section underwent continual postoperative antibiotic peritoneal lavage as an adjunct to surgery . In all the patients the indication for surgery was failure to respond to standard medical therapy . Seven patients treated with hysterectomy recovered without evidence of continuing peritonitis or intraabdominal abscess formation . One of two patients in whom uterine conservation was attempted required an emergency hysterectomy three days later . In this series, continual postoperative antibiotic peritoneal lavage appeared to be an effective adjunctive treatment in the prevention of continuing peritonitis and abscess formation provided that hysterectomy was performed at the initial operation. J Antibiot (Tokyo), 1984 Mar, 37(3), 227 - 34 Conformational flexibility of the methyltetrazolethiomethyl side chain of beta-lactam antibiotics . A computer graphics study; Boyd DB; Analysis of X-ray crystallographic data for cephalosporins and 1- oxacephalosporins shows that, although the 1-methyl-1H- tetrazol -5- ylthiomethyl side chain at position 3 of a bicyclic beta-lactam nucleus has certain conformational preferences, it also has considerable flexibility . Both the C4 = C3-C3'-S and C3-C3'-S-C5" torsional angles are frequently observed in the vicinity of +/- 90 degrees . The distance between the tetrazole ring carbon C5" and the 4-carboxyl carbon ranges from 4.07 to 5.65 A . Mean bond lengths and bond angles for the 3 and 4 side chains are tabulated. J Infect Dis, 1984 Mar, 149(3), 397 - 403 Effects of phagocytosis on antibiotic and nucleoside uptake by human polymorphonuclear leukocytes; Steinberg TH et al.; The ability of antibiotics to enter phagocytes during infection with facultative intracellular organisms was investigated using an in vitro model . Human polymorphonuclear leukocytes (PMNLs) were incubated with ingestible particles or phorbol myristate acetate (PMA), after which radiolabeled antibiotics were added to the cell suspension . Antibiotic uptake, determined by a velocity-gradient centrifugation technique, was expressed as the cellular:extracellular (C/E) antibiotic concentration ratio . Phagocytosis or PMA exposure enhanced PMNL clindamycin uptake (for example, C/E ratio of 12 for control vs 30 after zymosan) . Entry of penicillin was unaffected and erythromycin uptake was slightly decreased after phagocytosis . Because clindamycin uptake by phagocytes is mediated by the nucleoside transport system, adenosine uptake after phagocytosis was studied . Adenosine uptake was stimulated by phagocytosis, and this increase was inhibited by clindamycin . Thus, clindamycin uptake, mediated by the nucleoside transport system, was augmented by phagocytosis . This marked stimulation of a membrane transport system by phagocytosis has not been previously described. J Dairy Sci, 1984 Mar, 67(3), 707 - 12 Depletion of antibiotics from the mammary gland of goats; Long PE et al.; Four intramammary infusion products were tested in 10 normal goats to determine their rates of depletion from milk . The products tested, which are marketed for treatment of mastitis in the bovine, contained the single active ingredient erythromycin, oxytetracycline, penicillin, or cephapirin . Each mammary gland was infused, after the goats were milked, with the maximum recommended dose of test product (dosing frequency and quantity) for administration to lactating dairy cattle . With one exception, no antibiotics could be detected in the milk by the end of the bovine milk-discard period . Penicillin was detectable in the milk of one goat for 72 h after the last dose of product containing this antibiotic was given (60-h withdrawal period) . Only the product containing oxytetracycline produced significant adverse reactions in the mammary gland . The applicator tips of the products were too large for atraumatic insertion into the teat opening of some goats . Overall, results of this limited study indicated that some intramammary infusion products can be used to treat mastitis in the goat if instructions for use in the bovine are followed. Compr Ther, 1984 Mar, 10(3), 32 - 6 The role of infection in asthma: implications for antibiotic therapy; Pichurko BM et al.; Respiratory infection, most prominently bronchiolitis, contracted in infancy is frequently associated with recurrent wheezing episodes and asthma in later life . Atopic individuals and those with a family history of allergy or asthma in first-degree relatives are especially susceptible to the development of chronic airway dysfunction and should be identified early . It is also noteworthy that parenteral cigarette smoking may serve as an additional marker of the high-risk patient . Respiratory infection affecting older children and adults is more commonly due to rhinovirus and influenza A and may cause a transient hyperreactivity to bronchoconstrictor agonists, but does not cause persistent dysfunction . The mechanism(s) by which antecedent respiratory infection is related to recurrent wheezing and asthma remain speculative, and at present a direct causal relationship cannot be established with certainty . Infectious respiratory disorders are also a cause of exacerbations of asthma in adults but more commonly in children, and these also are primarily viral in origin . Consequently, in the absence of clear evidence of bacterial infection, routine antibiotic use in this setting is unwarranted. Am Surg, 1984 Mar, 50(3), 161 - 4 Prophylactic antibiotic usage in clean surgical procedures; Hoffman E; The article is a review of the results of a method of use of prophylactic antibiotic therapy in 2278 clean procedures performed by the author from 1959 to 1981 . The procedures analyzed are mastectomy, cholecystectomy, inguinal hernia repair, incisional hernia repair, laparotomy, and thyroidectomy . These cases are considered separately and compared with other detailed series in the literature . The author feels that the infection rate of 0% in this series when compared to rates of 1.7 per cent to 5 per cent in the literature for the same type of cases warrants use of this method . The major points in the method are 1) use of topical irrigating solution of 0.5 per cent neomycin sulfate; 2) beginning proper intravenous antibiotic administration when the patient reaches the recovery room; 3) limit the use of antibiotic to 3 days past the day of surgery unless drains or hemovacs are still in place, in which case the antibiotic is continued for 24 hours after their removal; 4) careful and strict daily examination and evaluation of the patient in order to discontinue the antibiotic at the outset of any problems; 5) continued strict adherence to basic surgical principles throughout the entire surgical experience of the patient. J Clin Pathol, 1984 Mar, 37(3), 321 - 8 Comparison of results from two antibiotic susceptibility testing trials that formed part of the United Kingdom national external quality assessment scheme; Snell JJ et al.; A susceptibility testing trial that formed part of the United Kingdom national external quality assessment scheme has been described previously . Results from this first trial showed an association between error rates and particular methods and practices . Changes in methods were recommended where appropriate . A second trial and survey of methods has shown reluctance to change methods and confirmed in most cases that high error rates were associated with the same methods and practices indicated by the first trial . Recommendations on disc content, method of methicillin testing, preparation of inoculum, use of controls and use of lysed blood for sulphonamide testing based on the results from these two trials are restated to encourage laboratories to review their methods critically . A statistical analysis of the results showed significant differences in performance among laboratories, and laboratories whose performance was significantly below the mean were identified . Poor performance was associated with the use of unsatisfactory methods . In view of the critical importance of susceptibility testing in patient care it is intended to use the results of susceptibility testing in the assessment of the performance of laboratories participating in the UK national external quality assessment scheme. Gan To Kagaku Ryoho, 1984 Mar, 11(3 Pt 2), 750 - 9 {Reversal of acquired resistance to vinca alkaloids and anthracycline antibiotics by calcium channel blockers and calmodulin inhibitors}; Tsuruo T; One of the major causes of failure in cancer chemotherapy is the selection and proliferation of specific drug-resistant tumor cells during treatment . The mechanism of acquired resistance of tumor cells to some agents is related to intracellular drug accumulation and retention . For example, in vincristine (VCR)- and adriamycin (ADM)-resistant tumor cell sublines, these agents can be shown to enter the cell but are actively transported to the outside . This results in a relatively low intracellular level of drug and thus to low cytotoxicity . These observations suggest that if we could control the VCR- and ADM-efflux function of resistant tumor cells appropriately, then we could expect a reversal of acquired resistance to these drugs in drug resistant tumor cells . We found that calcium channel blockers and calmodulin inhibitors enhance the intracellular level of vincristine and adriamycin in tumor cells, especially in drug-resistant mouse and human tumor cells by inhibiting their outward transport . The approach using calcium modifiers has the following advantages . (1) Reversal of acquired resistance to vinca alkaloids and anthracyclic antibiotics can be attained . Calcium channel blockers, such as verapamil, diltiazem, nicardipine, niludipine and nimodipine, at doses of 30 to 125 mg/kg administered daily for 10 days with VCR (10-200 micrograms/mg) enhanced the chemotherapeutic effect of VCB (40-50% increase in life span) in P388/VCR-bearing mice . The calcium channel blockers also enhanced the therapeutic effect of ADM in ADM resistant P388 bearing mice . (2) The approach is also effective for the reversal of the inherent resistance of tumor cells to anticancer agents . Less sensitive tumor cells became more susceptible to VCR and the heterogeneity in drug sensitivity among tumor clones has been circumvented . (3) The approach with these calcium modifiers is also effective against other antitumor agents which are transported outside the cells by the similar mechanisms . As one of the mechanisms of cross-resistance is explained by the enhanced drug efflux from resistant tumor cells, antitumor agents which show cross-resistance to VCR and ADM become effective against resistant tumor cells by this approach . The mechanism of this approach is now under investigation . These calcium modifiers enhance the cellular level of antitumor agents by inhibiting their outward transport . The functions of cellular calcium and calmodulin in the membrane architecture and membrane functions might be involved in this process . Clinical evaluation is now under progress by using diltiazen, nicardipine and verapamil. J Antibiot (Tokyo), 1984 Mar, 37(3), 211 - 7 Structures of OA-6129D and E, new carbapenam antibiotics; Yoshioka T et al.; The structures and stereochemistry of OA- 6129D and E, new carbapenam compounds produced by Streptomyces sp . OA-6129, were determined by spectroscopic analysis and chemical transformation. J Antibiot (Tokyo), 1984 Mar, 37(3), 200 - 6 Chicamycin, a new antitumor antibiotic . II . Structure determination of chicamycins A and B; Konishi M et al.; Structures of chicamycins A and B have been determined from a series of chemical degradation studies coupled with spectroscopic analysis . Chicamycin A is 2(S),11(R), 11a (S)-1,2,3,10, 11, 11a -hexahydro-2,8-dihydroxy-7,11-dimethoxy-5H-pyrrolo-{2,1-c} {1,4}-benzodiazepin-5-one, and chicamycin B is 2(S), 11a (S)-1,2,3, 11a -tetrahydro-2,8-dihydroxy-7 -methoxy-5H-pyrrolo-{2,1-c}{1,4}-benzodiazepin-5-one which is the demethanol form of chicamycin A . The structure of chicamycin B is closely related to that of neothramycin , differing only in the position of a hydroxyl substituent on the pyrrolidine ring. Mikrobiologiia, 1984 Mar-Apr, 53(2), 266 - 70 {Morphofunctional characteristics of the development of strains of Fusidium coccineum differing in antibiotic activity in stab cultivation}; Bartoshevich IuE et al.; The object of the work was to study the morphological and functional characteristics of Fusidium coccineum strains producing fusidic acid and differing in the antibiotic activity . The high metabolic activity of the culture is accompanied by the following morphological characteristics: the cells are rich in ribosomes and mitochondria, they have early vacuolisation, are filled with lipid granules, and then the mycelium undergoes autolysis . As strains with a high activity grow, the structure of the cells changes, the number of ribosomes and mitochondria falls down, and the latter are destroyed . For a long time, the cells contain electron-dense granular structures limited with the membrane and capable of transformation into lipid granules and membranous structures . As was shown by cytochemical studies, the structures have not merely proteins and lipids, but also phosphorus compounds . Their functional role in the fungal metabolism is discussed . As soon as super-synthesis of fusidic acid commences, the cells of the highly active strains are filled with lipid granules associated possibly with the steroid antibiotic . These formations are released from the cell during local lysis of the cell wall and the cytoplasmic membrane. J Gen Microbiol, 1984 Mar, 130 ( Pt 3), 575 - 82 Interactions of ribosomal antibiotics and informational suppressors of Aspergillus nidulans; Martinelli SD; Strains of Aspergillus nidulans containing informational suppressors were grown on medium containing antibiotics known to affect protein synthesis at the ribosomal level . These strains reacted in the anticipated manner: presumed ribosomal suppressors suaA101, suaA105, suaC109 and sua-115 were sensitive or even hypersensitive to aminoglycoside antibiotics, whereas presumed tRNA-like suppressors suaB111, suaD103 and D108 were only slightly sensitive or wild-type in response . Hygromycin and paromomycin were the most useful antibiotics . All the antibiotics reduced the colony radial growth rate, Kr, increased the lag phase and produced wrinkled morphology . Hygromycin was the most toxic . Resistant sectors were produced on paromomycin and hygromycin . The selective action of 'misreading' antibiotics on suaA and suaC strains is further evidence that these are ribosomal suppressors, whereas suaB and suaD may code for altered tRNA molecules . The results imply that hygromycin or paromomycin could be used for isolating ribosomal suppressors. Eur J Biochem, 1984 Mar 1, 139(2), 287 - 93 Labelling and cross-linking of Escherichia coli penicillin-binding proteins with bis-beta-lactam antibiotics; Rodriguez-Tebar A et al.; We have synthesized a number of radioactively labelled bis-beta-lactams, which are nearly symmetrical dimers of well-known beta-lactam antibiotics and act as bifunctional specific cross-linking reagents for the penicillin-binding proteins of Escherichia coli envelopes . We have observed that some of our bis-beta-lactam antibiotics cross-link two molecules of penicillin-binding protein 1b or 1c or 3 . Furthermore our bis-beta-lactam antibiotics bind to E . coli proteins with higher affinities than the beta-lactams from which they were derived . Therefore, a number of monomeric protein bands are consistently labelled with our bis-beta-lactam antibiotics (190, 170, 145 and 124 kDa) as well as the previously described penicillin-binding proteins 1a, 1b, 1c, 2, 3, 4, 5, 6, 7 and 8 . We do not know yet the possible enzymic activities of the penicillin-binding proteins of 190 kDa, 170 kDa, 145 kDa and 125 kDa that were not described previously . We have also detected some protein bands moving very slowly, which appear to be dimers or cross-linking species of these new high-molecular-mass penicillin-binding proteins described above. Am J Med, 1984 Mar, 76(3), 405 - 12 Effects of intensive induction chemotherapy for extensive-disease small cell bronchogenic carcinoma in protected environment-prophylactic antibiotic units; Valdivieso M et al.; Fifty-five patients with extensive-disease small cell bronchogenic carcinoma received three courses of intensive, inpatient, remission induction chemotherapy in (25 patients) or out (30 patients) of protected environment-prophylactic antibiotic (PEPA) units . Chemotherapy consisted of ECHO induction (E = epipodophyllotoxin VP-16-213; C = cyclophosphamide; H = hydroxydaunorubicin; O = Oncovin) and PRIME maintenance (PR = procarbazine; I = ifosfamide; ME = methotrexate) . All evaluable patients (22 in the protected environment group and 26 in the control group) had a complete (50 percent in the protected environment group and 54 percent in the control group) or partial (50 percent in the protected environment group and 46 percent in the control group) remission . Median response and survival durations for both treatment groups were similar . The median survival duration of patients with a complete remission favored the protected environment group (16.5 versus 12.67 months; p = 0.20) . Two patients (one from each group) are alive and disease-free for more than four years . Myelosuppression was intense and more pronounced in the protected environment group (p less than or equal to 0.01) . Infectious complications were less common in patients receiving intravenous prophylactic antibiotics and in those treated with intravenous antibiotics in PEPA units (p less than or equal to 0.04) . There were no treatment-related deaths, although treatment might have contributed to the death of three patients in the protected environment group and four in the control group . The administration of intensive ECHO induction chemotherapy to patients with extensive small cell bronchogenic carcinoma produced a high complete remission rate, although there was no significant long-term survival advantage over a program of less intensity . The administration of intravenous prophylactic antibiotics and the use of PEPA units significantly reduced the infectious morbidity of chemotherapy. Biochemistry, 1984 Feb 28, 23(5), 904 - 7 Evidence for the conversion of adenosine to 2'-deoxycoformycin by Streptomyces antibioticus; Hanvey JC et al.; The incorporation and distribution of 14C in 2'-deoxycoformycin, elaborated by Streptomyces antibioticus, were studied with {U-14C}glycine, {U-14C}adenosine and {U-14C}adenine . Similar ratios of 14C in the aglycon and carbohydrate portions of 2'-deoxycoformycin, ara-A, and adenosine isolated from the RNA indicated that {U-14C}adenosine was incorporated into 2'-deoxycoformycin without cleavage of the N-glycosylic bond . Following the addition of {U-14C}adenine, 98% of the 14C isolated from {14C}-2'-deoxycoformycin resided in the aglycon . 2'-Deoxycoformycin biosynthesis may not require the de novo purine biosynthetic pathway as evidenced by the failure to detect incorporation of {U-14C}glycine into 2'-deoxycoformycin . These data suggest that the biosynthesis of 2'-deoxycoformycin involves the incorporation of the carbon-nitrogen skeleton of an intact purine nucleoside or nucleotide, thereby implying that a purine ring is opened enzymatically between C-6 and N-1 and a one-carbon unit is added to form the 1,3-diazepine ring of 2'-deoxycoformycin. Biochem Pharmacol, 1984 Feb 15, 33(4), 629 - 37 Interactions of aminoglycoside antibiotics with negatively charged lipid layers . Biochemical and conformational studies; Brasseur R et al.; Previous studies {Laurent et al., Biochem . Pharmac . 31, 3861 (1982)} have demonstrated that aminoglycoside antibiotics bind to negatively charged phospholipid bilayers and inhibit the activity of lysosomal phospholipases . This inhibition also occurs in vivo in animal and man . It is considered to be an early and significant step in the development of aminoglycoside-induced nephrotoxicity . The binding of 6 aminoglycosides in current clinical use (dibekacin, gentamicin, tobramycin, kanamycin A, amikacin and streptomycin) to phosphatidylinositol has been studied by gel filtration technique and by conformational analysis . Variation of the phosphatidylinositol content from 0 to 27% of total phospholipids causes a cooperative increase in aminoglycoside binding . At fixed phosphatidylinositol concentration, the binding of the different aminoglycosides is related to the number of aminogroups carried by the drug (viz., gentamicin greater than kanamycin A greater than streptomycin) and is largely, but not entirely dependent upon electrostatic interactions . Conformational analysis of the interaction of aminoglycosides with phosphatidylinositol monolayers was made by a step-wise computation approach . We first have taken into account the Vander Waals, torsional and electrostatic energies and we have calculated the hydrophobic and hydrophilic centers of each molecule . Assembly was then computed by successive association of one molecule of drug and up to 4 molecules of phosphatidylinositol . The calculated interaction energies varied from -8.5 kcal/mol (gentamicin) to -4.9 kcal/mol (amikacin) and -3.9 kcal/mol (streptomycin).(ABSTRACT TRUNCATED AT 250 WORDS) Biochem Pharmacol, 1984 Feb 15, 33(4), 523 - 6 Clavines . New antibiotics with cytostatic activity; Eich E et al.; The cytostatic potentials of ten ergolines were determined in the L5178y mouse lymphoma cell system; six of them belong to the clavines (agroclavine, 1-propyl-agroclavine, 1-propyl-festuclavine, 1-allyl-festuclavine, 6-cyano-6-nor-festuclavine and 1-hydroxymethyl-festuclavine) and four to the lysergic acid derivatives (methylergometrine, lysergic acid amide, isolysergic acid amide and lysergic acid diethylamide) . It is shown that agroclavine (ED50: 3.9 microM), 1-propyl-agroclavine (3.5 microM), 1-propylfestuclavine (4.3 microM) and 1-allyl-festuclavine (4.3 microM) are potent cytostatic agents . Up to 2 X ED50 concentration the inhibitory effect was completely reversible . Incorporation studies suggested that the compounds inhibit DNA synthesis; this assumption was also supported by the findings which revealed that after incubation with these clavines, the cells showed slight 'unbalanced growth' . 6-Cyano-6-nor-festuclavine was less inhibitory (ED50 11.8 microM) . 1-Hydroxymethyl-festuclavine and all lysergic acid derivatives tested were without any detectable activity. Jpn J Antibiot, 1984 Feb, 37(2), 261 - 6 {Penetration of cefbuperazone, a new cephamycin antibiotic, into human peritoneal exudate}; Watanabe Y et al.; Pharmacokinetic studies were carried out on cefbuperazone ( CBPZ ) in 9 patients undergoing postoperative drainage . The concentration of CBPZ in serum and peritoneal exudate after one shot intravenous administration of 1 g was measured by bioassay and calculated respectively by two- and one-compartment open model . The results obtained were as follows: The pharmacokinetic parameters calculated from the serum levels were compared to those reported previously; T1/2 = 101 min., Vd = 4.06 L and Cl = 76 ml/min . The simulation curve of the peritoneal exudate level fit fairly with the mean values of 6 patients . It appeared that CBPZ penetrated somewhat slowly into peritoneal exudate with the peak value of 27.05 micrograms/ml at about 1 hour after the administration . The exudate levels thereafter declined more slowly than the serum ones (T1/2 = 134 min.) . IT was 6.2 micrograms/ml even at 6 hours after the administration. J Antibiot (Tokyo), 1984 Feb, 37(2), 127 - 9 Deepoxidation of 16-membered epoxyenone macrolide antibiotics . II . Chemical deepoxidation by dissolving metal reduction; Mutoh Y et al.; 16-Membered epoxyenone macrolide antibiotics were reductively deepoxidized with dissolving metals such as zinc . Angolamycin and rosamicin which have a methyl substituent at C-12 in the epoxyenone structure were deepoxidized, but not isomerized further to the geometric isomers P2 and P3. Antibiotiki, 1984 Feb, 29(2), 83 - 5 {Stability of the antibiotic formation trait of the tobramycin producer Streptomyces cremeus subsp . tobramycini}; Motkova MO et al.; The stability of the tobramycin-producing organism was studied by the property of the antibiotic production . The organism was stored under conditions of different exposures to light and subculture on slants . The culture was also subjected to long-term storage with various methods . The organism was stable in preserving its antibiotic activity for 1.5 months when stored on the Gauze organic agar No . 2 . Subcultures of the organism on this medium provided preservation of the antibiotic activity throughout 4 passages . The culture storage on millet provided preservation of the antibiotic activity for 6 months. Antibiotiki, 1984 Feb, 29(2), 132 - 5 {Effect of sodium nucleinate on the effectiveness of antibiotic therapy of erysipelas}; Frolov VM et al.; The clinical effect of sodium nucleinate (SN) was investigated by comparison of the clinico-laboratory findings in 70 patients treated with this drug during the acute stage of erysipelas in addition to antibiotic therapy and the same tests in 100 patients treated with the antibiotics alone . It was shown that SN had a favourable therapeutic effect on the patients with erysipelas . It accelerated the elimination of the local inflammation foci and lowered the incidence of relapses . The therapeutic effect of SN was due to its stimulating effect on the cell and humoral immunity and natural resistance to infection . The results of the study allowed recommending the use of SN in combined therapy of erysipelas for increasing the antibiotic efficacy. J Pediatr Surg, 1984 Feb, 19(1), 84 - 6 Bioavailability of oral antibiotics in children with short-bowel syndrome; Menardi G et al.; Absorption of orally administered antibiotics (two aminopenicillins, cephalexin, trimethoprim-sulfa) was investigated in five children with sizeable resection of small bowel in the neonatal period . The absorption was proportional to the length of the remaining bowel and independent from the resected part of the gut . For cephalexin and trimethoprim a reduction of the absorption of 10% to 50% was observed, still resulting in therapeutic serum concentrations . The absorption of aminopenicillin was reduced approximately 10% of the usually achievable concentrations . Our data suggest that oral cephalexin and trimethoprim-sulfa can be used therapeutically in children with short-bowel syndrome . If aminopenicillin is indicated, parenteral therapy is advisable. Toxicol Appl Pharmacol, 1984 Feb, 72(2), 195 - 200 Tapetal changes in beagle dogs . II . Ocular changes after intravenous administration of a macrolide antibiotic--rosaramicin; Massa T et al.; Two studies were conducted to assess the toxicity of rosaramicin (a macrolide antibiotic) when given intravenously for 30 consecutive days to beagle dogs with and without a tapetum lucidum (a light reflecting structure within the choroid of the eye) . In the initial study, groups of three tapetal dogs/sex were given 20, 40, or 80 mg of rosaramicin/kg, twice daily . Ophthalmoscopic examination during Week 4 revealed dose-related, bilateral ocular changes characterized by a brown-tan discoloration and general pallor or loss of reflectivity of the normally blue-purple or yellow-green, highly reflective tapetum lucidum . These findings were restricted to the tapetal fundus; recovery occurred between Weeks 4 and 10 of the postdose period . To further investigate these changes, a second study was conducted in which groups of three tapetal dogs were given rosaramicin or erythromycin lactobionate (comparative macrolide antibiotic) at 80 mg/kg, twice daily . A third group of atapetal dogs was given 80 mg of rosaramicin/kg, twice daily . A similar change was observed in tapetal dogs given 80 mg of rosaramicin/kg, twice daily, in the follow-up study, but not in the other two groups . No other compound-related changes were observed in either study . The ocular changes observed in dogs given rosaramicin were reversible and structure-specific, occurring only in animals possessing a tapetum lucidum. J Lab Clin Med, 1984 Feb, 103(2), 294 - 303 The influence of aminoglycoside antibiotics on the in vitro function of rat liver ribosomes; Loveless MO et al.; There are few studies of the influence of aminoglycoside antibiotics on the ribosomes of higher eukaryotic organisms . To this end, cytoplasmic ribosomes were prepared from rat liver . In vitro, poly(U)-directed ribosome protein synthesis was studied in the presence and absence of selected aminoglycosides . Misreading of poly(U) was also assessed . Consistent with earlier studies using different sources of ribosomes, paromomycin inhibited cell-free protein synthesis and caused poly(U) misreading . In contrast to the findings of other studies in cell-free ribosomes of eukaryotic organisms, netilmicin, tobramycin, and neomycin were most active in inhibiting protein synthesis, and gentamicin C2 and neomycin caused appreciable misreading . Thus the previous suggestion that a paromamine fragment (found in paromomycin) might be a structural requirement for in vitro inhibition of protein synthesis and misreading is not substantiated by the results in rat liver ribosomes . Commercial gentamicin C is a mixture of gentamicins C1, C1a, and C2 . Despite nearly identical chemical structures, the three constituents displayed greatly different propensities for inducing poly(U) misreading . C2 was the most active, followed by C1a . In summary, selected aminoglycoside antibiotics caused inhibition and mistranslation of poly(U) messenger in an in vitro ribosome system prepared from rat liver . These effects were not limited to paromamine-containing aminoglycoside antibiotics . Gentamicin C2 caused much more poly(U) misreading than the other two constituents of the gentamicin C complex. J Bacteriol, 1984 Feb, 157(2), 507 - 13 Production and release of peptidoglycan and wall teichoic acid polymers in pneumococci treated with beta-lactam antibiotics; Fischer H et al.; Autolysin-defective pneumococci treated with inhibitory concentrations of penicillin and other beta-lactam antibiotics continued to produce non-cross-linked peptidoglycan and cell wall teichoic acid polymers, the majority of which were released into the surrounding medium . The released cell wall polymers were those synthesized by the pneumococci after the addition of the antibiotics . The peptidoglycan and wall teichoic acid chains released were not linked to one another; they could be separated by affinity chromatography on an agarose-linked phosphorylcholine-specific myeloma protein column . Omission of choline, a nutritional requirement and component of the pneumococcal teichoic acid, from the medium inhibited both teichoic acid and peptidoglycan synthesis and release . These observations are discussed in terms of plausible mechanisms for the coordination between the biosynthesis of peptidoglycan and cell wall teichoic acids. Lab Anim Sci, 1984 Feb, 34(1), 94 - 6 External application of antibiotic to improve survival of adult laboratory frogs (Rana pipiens); Menard MR; Survival data for over 500 adult frogs (393 Rana pipiens, 35 Rana clamitans , and 97 Rana temporaria) obtained from commercial suppliers were accumulated . Frogs which developed signs of red-leg disease while being kept in 0.15% saline were cured by addition of appropriate antibiotics to the saline . The appropriate antibiotic was determined by sensitivity testing of bacteria isolated from the sick frogs . When many frogs in a shipment were sick, prophylactic treatment of the entire shipment improved the overall survival in the shipment. J Natl Cancer Inst, 1984 Feb, 72(2), 435 - 9 Potentiation of cytotoxicity of anticancer agents by several different polyene antibiotics; Valeriote F et al.; The ability of several different polyenes to potentiate the cytotoxicity of carmustine, lomustine (LOM), and doxorubicin (DX) against AKR mouse leukemia was quantitated . All polyenes could potentiate the cytotoxicity of the anticancer agents; however, the methyl ester derivatives of the heptaenes amphotericin B and candicidin and the triene trienine were most effective with potentiations in the order of ten thousandfold for DX and LOM . A steep dose-response relationship for the polyenes was also noted . Neither the toxicity of the polyenes nor their level of potentiation could be correlated with structure or class. Biokhimiia, 1984 Feb, 49(2), 254 - 60 {Inhibition by antibiotics of the incorporation of labelled amino acids into the nuclear matrix proteins of the Zajdela hepatoma}; Bazarnova TM et al.; The incorporation of radioactivity into nuclear matrix proteins during incubation of Zajdela hepatoma cells with labelled amino acids was strongly inhibited by chloramphenicol and cycloheximide and slightly inhibited by actinomycin D and mitomycin C . The antibiotics studied inhibited the incorporation of the radioactive label preferentially into proteins with Mr 150 000-220 000, approximately 55 000 and less than 26 000 . During incubation of ascites tumour cells with antibiotics, predominantly with chloramphenicol, a decrease in the content of some protein components was observed as well . As in the low molecular weight protein fraction, the intense inhibition of the radioactive label and a decrease of its content was observed, a conclusion is drawn that this protein fraction is characterized by a high turnover rate. Immun Infekt, 1984 Feb, 12(1), 61 - 4 {Effect of immunoglobulin and antibiotic in E . coli infection of malnourished mice}; Viell B et al.; Malnourished mice, which exert a greater susceptibility to E.coli induced intraperitoneal infection than standard fed animals, cannot be protected by application of immunoglobulin (2 X 10(5) cells/animal) . If, however, an antibiotic (mezlocillin, 500 mg/kg s.c.) is given shortly after infection, the surviving rate increases dramatically to 42% . This effect is enhanced to 63% survival, if the infected animals receive an additional dose of immunoglobulin. Ann Trop Med Parasitol, 1984 Feb, 78(1), 1 - 11 Combination of the antibiotics erythromycin and tetracycline with three standard antimalarials against Plasmodium falciparum in vitro; Gershon PD et al.; Combinations of antibiotics and standard antimalarials have been assayed against P . falciparum in vitro, using incorporation of 14C isoleucine as an indicator of drug action . Chloroquine and erythromycin have been shown to act synergistically against a chloroquine-resistant strain and additively towards a chloroquine-sensitive strain, confirming their action against sensitive and resistant P . berghei in vivo, described elsewhere . Combinations of erythromycin with mefloquine or quinine acted anergically in 24 hour assays in which unphysiologically high concentrations of quinolinemethanol were necessary for demonstrable drug effect . In 48 hour assays, an additive effect was obtained with these combinations . Tetracycline is additive in combination with each of the standard antimalarials used in this study . The relevance of results obtained in vitro to parasite drug sensitivities in vivo is discussed. Genetika, 1984 Feb, 20(2), 212 - 8 {Isolation of a yeast vector marked by the mutation of multiple resistance to antibiotics}; Nevzgliadova OV et al.; The plasmid mutation AntR determining multiple resistance to antibiotics--tetracycline and cycloheximide in Saccharomyces cerevisiae was earlier obtained and genetically characterized . In this work we describe experiments on cytoduction and transformation, proving the localization of this mutation in the yeast 2 mu DNA . As a result of cotransformation of the sensitive cells carrying a double mutation in the gene LEU2 with the yeast vector marked by LEU2 and 2 mu DNA obtained from the yeast AntR mutant, the Leu+ AntR clones were selected . Though the primary co-transformans contain both plasmids in an unlinked state, we managed to get clones in which the markers AntR and LEU2 were linked . The putative recombinant molecules were cloned in Escherichia coli and then introduced into the yeast recipient cells, differing by the presence of the endogenous 2 mu DNA . Retransformation of cir0 cells results in the appearance of the clones in which LEU2 and AntR markers segregate together . Thus, the result of cotransformation and selection in vivo is that the mutation of multiple resistance was included into the yeast vector plasmid, presumably, in its 2 mu part. Int J Appl Radiat Isot, 1984 Feb, 35(2), 103 - 9 Semi-automated preparation of a 11C-labelled antibiotic--{N-methyl-11C}erythromycin A lactobionate; Pike VW et al.; A fast semi-automated method is described for labeling the antibiotic, erythromycin A (1), with the short-lived positron-emitting radionuclide, 11C (t 1/2 = 20.4 min), in order to permit the non-invasive study of its tissue uptake in vivo . Labelling was achieved by the fast reductive methylation of N-demethylerythromycin A (2) with {11C}formaldehyde, itself prepared from cyclotron-produced {11C}-carbon dioxide . Rapid chemical and radiochemical purification of the {N-methyl-11C}erythromycin A (3) were achieved by HPLC and verified by TLC with autoradiography . The purified material was formulated for human i.v . injection as a sterile apyrogenic solution of the lactobionate salt . The preparation takes 42 min from the end of radionuclide production and from {11C}carbon dioxide produces {N-methyl-C11}erythromycin A lactobionate in 1-12% radiochemical yield, corrected for radioactive decay. Thorac Cardiovasc Surg, 1984 Feb, 32(1), 10 - 4 "Fresh", antibiotic sterilized aortic homografts in extracardiac valved conduits . Long-term results; di Carlo D et al.; Between 1971 and 1980, 65 children, aged 2 weeks to 15 years (mean 6.8 years) had "fresh" antibiotic sterilized aortic homografts inserted as a valved external conduit . Thirty-six patients (55%) had undergone previous palliations . Operations were performed on cardiopulmonary bypass, with hypothermia and cardioplegia . In selected young infants, deep hypothermia with circulatory arrest was used . Twenty-five patients (38%) died after the operation . Mortality was related to the complexity of the lesion, the condition of the child on admission, and the degree of pulmonary vascular disease . In addition, there were 7 late deaths . Twenty-one patients were recatheterized, either as a part of routine postoperative assessment (13) or because of symptoms (8) . Satisfactory conduit performance, judged by the absence of significant gradients or regurgitation, was found in 18 out of 21 restudied patients . Calcification of the homograft aortic wall was seen on chest X-ray in 56% of patients . The aortic valve calcified in only one child, following an episode of subacute bacterial endocarditis . We conclude that fresh antibiotic preserved aortic homografts perform well in extracardiac valved conduits . They are easy to insert and better hemostasis can be achieved . Degeneration of the valved leaflets is extremely rare. Chemioterapia, 1984 Feb, 3(1), 33 - 40 Antibiotic nephrotoxicity; Morin JP et al.; Antibiotics are the principal cause of drug-associated nephropathy . They are responsible for acute interstitial nephropathy (AIN) or acute tubulo-interstitial nephropathy (ATIN) due to two different pathophysiologic mechanisms: a drug-induced immunologic process and direct action due to drug accumulation . 1) Ain of immunologic origin . These are rare and are induced either by beta-lactamines or by rifampicin . Among the beta-lactamines, methicillin is the most often responsible, while penicillin and ampicillin are less often, and only rarely are carbenicillin, oxacillin, nafcillin, cephalothin and cephalexin . Macroscopic hematuria occurring 10 to 15 days after initiation of treatment usually reveals the renal involvement . It is associated with or preceded by fever, skin eruption and blood eosinophilia . Renal insufficiency (RI) is not severe and rarely requires hemodialysis (HD) . The course is usually favorable . Rifampicin-induced AIN is observed in two circumstances, either during intermittent treatment or when previous treatment is resumed . Macroscopic hematuria is rare and RI often severe . Anti-rifampicin anti-bodies are usually found . 2) ATIN due to direct toxicity . Several classes of antibiotics may be responsible: cephalosporins, polymyxins or cyclins, but it is usually observed with aminoglycosides (AG) . The incidence of renal involvement due to the latter group is estimated to be 4 to 10% . Nephrotoxicity is initially reflected by polyuria, tubular proteinuria and increased enzymuria, followed by cylindruria and reduced glomerular filtration . HD is rarely required . The proximal tubule is predominantly affected; pathological findings are disappearance of the brush border and tubular necrosis . Electronic microscopy shows lysosomal alterations with numerous myelinic bodies . Tubular regeneration occurs within 15 to 30 days.(ABSTRACT TRUNCATED AT 250 WORDS) S Afr Med J, 1984 Jan 28, 65(4), 121 - 2 Antibiotic therapy in acute infections of bone and joints in children; Learmonth ID et al.; Effective antibiotic therapy forms the mainstay of the treatment of acute bone and joint infections in children . The causal organisms and bacterial sensitivities encountered in a prospective study are presented . Initial antibiotic therapy is discussed, while the need for immediate Gram staining to identify resistant organisms is stressed. Biol Res Pregnancy Perinatol, 1984, 5(2), 57 - 60 Transfer of antibiotics into maternal milk; Matsuda S; Thirty antibiotics, including penicillins, cephems, chloramphenicol, tetracyclines, macrolides, and aminoglycosides, were given p.o., i.m . or i.v . once to 70 puerperal women to compare milk drug levels with serum levels over a 6-h period . Antibiotic transfer into the milk was small . No drugs except for a few (chloramphenicol, tetracyclines, macrolides) reached the level of 1 mcg/ml or greater . Penicillins and cephams detected in trace amounts in the milk are likely to have little effect on infants. Biochem Pharmacol, 1984 Jan 1, 33(1), 41 - 6 Haemolytic activity of aromatic heptaenes . A group of polyene macrolide antifungal antibiotics; Cybulska B et al.; The aromatic heptaene vacidin A induces ion selective channels in human red blood cells . The ion flux induced leads to a secondary effect--colloid osmotic haemolysis . Molecular variations at ionizable polar groups of the antibiotic modify the properties of the permeability pathway concerning intercationic selectivity and the symmetry of ion flux. J Antimicrob Chemother, 1984 Jan, 13(1), 31 - 43 Relative inhibition factors--a novel approach to the assessment of antifungal antibiotics in vitro; Odds FC et al.; A system is described for measurement of relative inhibition factors (RIFs) for antifungal agents--that is, the area under a fixed portion of the antifungal dose-response curve, expressed as a percentage of the area under the dose-response curve for a theoretical noninhibitory substance . The RIFs for two polyenes, 5-fluorocytosine (5FC) and griseofulvin correlated with the known inhibitory activity of these compounds against pathogenic yeasts, Aspergillus spp . and dermatophytes in vitro and in vivo, but revealed wholly new relative inhibitory properties among five imidazole antifungals: ketoconazole and tioconazole emerged as the most active imidazole antifungals against yeasts and clotrimazole and econazole against Aspergillus spp . Because of the high reproducibility of the assay, and because tests were done in a tissue culture medium in the presence of serum, it is considered that measurement of RIFs could give better predictions of likely antifungal activity in vivo than is at present afforded by tests for minimal inhibitory concentrations. J Antibiot (Tokyo), 1984 Jan, 37(1), 63 - 70 Preliminary toxicity studies with the DNA-binding antibiotic, CC-1065; McGovren JP et al.; It was previously shown that the potent new DNA-binding antibiotic, CC-1065, prolonged life span, but was not curative, when administered to mice bearing a variety of transplantable tumors . In this paper we show results of preliminary studies indicating that CC-1065 caused lethal delayed hepatotoxicity at therapeutic antineoplastic doses . In non-tumor-bearing mice toxic deaths were delayed ca 50 days after a single iv dose of 12.5 micrograms/kg and as much as 70 days after 10 micrograms/kg was given ip . Intravenous mouse LD50's were 9 micrograms/kg, single dose, and 0.3 microgram/kg/day, five daily doses . Intraperitoneal LD50's were 0.53 approximately 6.90 micrograms/kg, single dose, and 0.14 microgram/kg/day, five daily doses . Mice treated with high doses iv died within 12 days with frank hepatic necrosis, whereas delayed deaths at lower doses were associated with changes in hepatic mitochondrial morphology . This suggested that separate mechanisms of hepatotoxicity were operative at high and low dose ranges . Attempts to prevent the delayed toxicity of CC-1065 in the mouse by treatment with WR-2721, N-acetylcysteine, phenobarbital, Aroclor 1254, and 3-methylcholanthrene were unsuccessful; no effect on the LD50 or the times of death was observed . Lethal doses in the rabbit were similar on a body surface area basis to those in the mouse; evidence of hepatotoxicity was also observed in the rabbit. Antibiotiki, 1984 Jan, 29(1), 7 - 14 {Isolation and study of the antibiotics produced by a culture of Str . iverini (Gause et al., 1957) Pridham et al., 1958}; Frolova VI et al.; An antibiotic complex consisting of echinomycin and triostin A was isolated from Str . iverini (Gauze et al., 1957) Pridham et al., 1958 . Hydrolysis of the antibiotics resulted in formation of an aglycone identified with quinoxaline carboxylic acid . The UV spectrum of the aglycone and the antibiotics of the echinomycin-triostin group was studied. Antibiotiki, 1984 Jan, 29(1), 3 - 7 {New species of Actinomadura recticatena sp . nov . and its antibiotic properties}; Gauze GF et al.; Actinomadura cultures were isolated from soil samples collected in Turkmenistan, the Moscow, Kursk and Volgograd regions . The cultures were described as representatives of a new species (Actinomadura recticatena, Preobrazhenskaya et Galatenko, sp . nov) . The hydrolysates of intact cells of the cultures contain mesodiaminopumelic acid, galactose and madurose . The species is characterized by straight spore chains, wrinkled spore surface, cream-colored aerial mycelium and brown substrate mycelium with pinkish or slightly violet shade . The cultures produce no soluble pigments, including the melanoid ones . The red-violet fraction of the pigments responsible for the pinkish and violet shades of the substrate mycelium belongs to the antibiotics of the griseorodin-rubromycin group. Ann Surg, 1984 Jan, 199(1), 107 - 11 The influence of prophylactic antibiotics on the warfarin anticoagulation response in the postoperative prosthetic cardiac valve patient . Cefamandole versus vancomycin; Angaran DM et al.; The influence of cefamandole and vancomycin used for prophylaxis on the warfarin anticoagulation response in 60 cardiac valve replacement patients during the postoperative period is presented . Patients were divided into two groups, hyper-responders prothrombin time (PT) greater than or equal to 32 sec, 48 hr after the initial warfarin dose (GrIHR), or normal responders PT less than 32 sec (GrIINR) . Fifteen patients (25%) were in GrIHR (PT 44.3 +/- 10.5) and 45 in GrIINR (21 +/- 5) . Fourteen of the 15 GrIHR patients received cefamandole and 1 of the 15 GrIHR patients received vancomycin p less than 0.05, as prophylaxis . Warfarin sensitivity was assessed using a warfarin dose index (WDI) calculated in the initial postoperative period (WDIINT) and at discharge (WDIDIS) . GrIHR patients had greater WDIINT and WDIDIS compared to GrIINR p less than 0.001 . Baseline prothrombin time measured 8 hours prior to start of warfarin therapy (PTBL), was linearly correlated to the WDIINT with r = 0.8, p less than 0.001 in cefamandole patients only . The data suggests that cefamandole increases warfarin sensitivity early in the postoperative course of oral anticoagulation therapy, which may lead to excessively high prothrombin times with the possibility for serious bleeding. J Bacteriol, 1984 Jan, 157(1), 337 - 40 Regulatory mutants of Streptomyces clavuligerus affected in free diaminopimelic acid content and antibiotic biosynthesis; Aharonowitz Y et al.; The composition of intracellular free amino acid pools was determined in Streptomyces clavuligerus mutants possessing an altered aspartokinase which is insensitive to concerted feedback inhibition by threonine and lysine . These mutants contained total free amino acid pool contents that were considerably higher than those found in the wild-type strain . Diaminopimelic acid accounted for 10 to 20% of the total free amino acid pools, depending on the individual mutant and its culture growth phase, whereas diaminopimelic acid contained in the wild-type strain accounted for only 0.5% of the total free amino acid pool. J Antimicrob Chemother, 1984 Jan, 13(1), 45 - 54 3-Dimensional susceptibility testing of beta-lactam antibiotics; Thomson KS et al.; A technique for demonstrating the substrate specificities of bacterial beta-lactamases is presented . Enzymatic degradation of beta-lactam antibiotics can be detected by cutting a wall of inoculum into the agar 3 mm from an antibiotic disc . Inactivation of the drug as it diffuses through the wall of inoculum results in distortion of the resulting inhibition zone . This procedure can be applied to the Stokes, Bauer-Kirby, International Collaborative Study (ICS) and Calibrated Dichotomous Sensitivity Test (CDS) methods so that they provide information about any detrimental effect of a pathogen on beta-lactam antibiotics, in addition to the effect the antibiotics have on the pathogen . The additional information generated by this simple procedure should increase the predictive value of in-vitro tests. Antibiotiki, 1984 Jan, 29(1), 14 - 9 {Penicillinase from B . licheniformis . Determination of the ionization constants of the enzymatic hydrolysis products of beta-lactam antibiotics}; Satarova DE et al.; The level of transformation of beta-lactam antibiotics hydrolysed by penicillinase from B . licheniformis on determination with the method of pH-metric titration with sodium hydrate solutions depended on the electrochemical nature of the products formed . The data on the study of the pH dependence of the penicillinase-catalysed hydrolysis of beta-lactam antibiotics were used for estimation of the ionization constants of the products of the enzymatic hydrolysis of the beta-lactam ring in the molecules of azlocillin, carfecillin, benzylpenicillin, cephalothin and 7-PADCA . Methods for quantitative determination of the compounds were developed . The methods are based on penicillinase-catalysed enzymatic hydrolysis and pH-metric titration of the products with sodium hydrate solutions at pH 7.0 with regard to their dissociation levels. Scand J Infect Dis Suppl, 1984, 42, 83 - 98 Pharmacokinetics of beta-lactam antibiotics; Bergan T; Beta-lactam antibiotics represent the oldest class of antibiotics used in the treatment of infections . Consequently, a large number of agents have been developed . Penicillins and cephalosporins are generally available for parenteral application . Some are absorbed from the gastrointestinal tract . The serum half-life (t1/2) of most beta-lactams is 1-2 hours . Ceftazidime and temocillin are more long-lasting with a t1/2 of 4-6 hours and ceftriaxone of 8-10 h . These values relate to patients with normal renal function . The elimination is only moderately prolonged for beta-lactams and of little consequences for the dosage regimens, partly because of the high tolerance of this group of antibiotics . Penicillins and cephalosporins are eliminated by glomerular filtration and varying degrees of active transport across the epithelial cells of the renal tubuli and hepatobiliary system . Active transport mechanisms also explain the low concentrations of beta-lactam antibiotics in cerebrospinal fluid . Otherwise, penetration of these agents to unspecialized tissues is good . Substances with a low serum protein binding, such as ampicillin and amoxicillin, reach concentrations in peripheral human lymph which as assessed by the ratios of areas under the concentration curves are 50-80% of the serum levels . The serum protein binding appears to act mainly by inhibiting the rate with which the antibiotic passes into extravascular foci . For instance, temocillin with a serum albumin binding around 85% establishes levels in peripheral lymph which are 50-60% of those in serum . This may be explained by the fact that a higher protein binding is accompanied by more lipid solubility, which are two factors acting in opposite directions as concerns passage by diffusion across body barriers. Scand J Infect Dis Suppl, 1984, 42, 17 - 37 Bacterial wall peptidoglycan, DD-peptidases and beta-lactam antibiotics; Ghuysen JM et al.; Wall peptidoglycan expansion in bacteria rests upon a cytoplasmic D-Ala: D-Ala ligase (ADP) which catalyses synthesis of a D-Ala-D-Ala dipeptide (with accompanying hydrolysis of one molecule of ATP) and a set of DD-peptidases which utilize this D-Ala-D-Ala dipeptide--once it has been translocated at the outer face of the plasma membrane as the C-terminal portion of a disaccharide peptide unit--as carbonyl donor for transpeptidation and carboxypeptidation reactions (without additional energy expenditure) . Four DD-peptidases have been selected which differ from each other with respect to the effects that amino compounds exert on the fate and rate of consumption of a D-Ala-D-Ala terminated amide carbonyl donor analogue . They serve as models to understand the different mechanisms by which the DD-peptidases perform catalysis and show widely varying responses to the action of beta-lactams, from extreme sensitivity to very high resistance. Arch Toxicol Suppl, 1984, 7, 282 - 5 In vitro inhibition of lysosomal phospholipases by aminoglycoside antibiotics: a comparative study; Carlier MB et al.; Aminoglycosides induce an early and characteristic phospholipidosis in the lysosomes of kidney tubular cells . Inhibition of lysosomal phospholipase activity by gentamicin has been demonstrated in vivo and in vitro . Ten aminoglycosides have been examined for their potency in inhibiting phospholipases A1 and A2 . Similar IC50's and IC90's (concentrations causing 50 and 90% inhibition) were found for sisomicin, dibekacin, gentamicin, tobramycin, kanamycin B and netilmicin . Kanamycin A, HABA-dibekacin and amikacin showed increasingly higher IC's . Thus, both the number and the position of amino groups are important . Streptomycin had little effect on phosphatidylcholine hydrolysis . Kinetic studies with gentamicin suggest a competitive type of inhibition . This approach may help for the in vitro screening of less toxic aminoglycosides. Geburtshilfe Frauenheilkd, 1984 Jan, 44(1), 8 - 13 {Effectiveness of pre-operative antibiotic prevention in hysterectomies and cesarean section}; Hirsch HA et al.; All controlled studies which were available by computer search from the literature were evaluated regarding the efficiency of preventive antibiotics for post-operative infections following hysterectomies and Cesarian sections . All controlled studies were evaluated by identical criteria . In 41 out of 46 studies (89.1%) on vaginal hysterectomies, febrile morbidity showed a significant decrease . In abdominal hysterectomies, 15 of 26 studies (57.7%) and in Cesarian sections 47 of 53 studies (88.7%) showed a significant decrease . Following vaginal hysterectomies and Cesarian sections, the preventive antibiotics decreased the febrile morbidity by 26 or 26.9 percentage points and pelvic or uterine infections by about 20 percentage points . In abdominal hysterectomies, the decrease was only 10.4 or 4.4 percentage points . Cesarian sections after the onset of labour and or rupture of the membranes have a high risk of infection and show the best decrease of febrile morbidity following preventive antibiotics. Scand J Infect Dis, 1984, 16(1), 61 - 71 Sensitivity of 523 blood culture isolates to 33 antibiotics; Ode B et al.; 523 blood culture isolates collected during 18 months (July 1980-December 1981) were analysed by the agar dilution method for sensitivity to 33 antibiotics . Breakpoints corresponding to the SIR system were used but for N-formimidoyl-thienamycin (N-f-thienamycin), azthreonam and fosfomycin serial dilutions were made . Aminoglycosides (netilmicin, gentamicin, amikacin and tobramycin) inhibited from 90 to 86% of the strains . This was comparable to the percentage inhibited by some cephalosporins (cefotaxime, cefoperazone, ceftazidime, ceftriaxone, cefuroxime, cephamandole and moxalactam) ranging from 95 to 89% . A very high number of strains (99%) were inhibited by N-f-thienamycin . By combination of certain antibiotics more than 99% of the strains could be inhibited. Comput Biol Med, 1984, 14(4), 457 - 62 Computer programs to obtain HPLC parameters of beta-lactam antibiotics; Prieto JG et al.; Listings of BASIC and TI-59 programs are included to obtain the HPLC retention factors for beta-lactam antibiotics at given antibiotic pK's, pH, and capacity factor values, which are useful in considering the different chromatographic behaviour of antibiotics as the pH varies. J Antibiot (Tokyo), 1984 Jan, 37(1), 1 - 5 Studies on a new nucleoside antibiotic, dapiramicin . II . Isolation, physico-chemical and biological characterization; Nishizawa N et al.; New nucleoside antibiotics, dapiramicins A and B produced by a Micromonospora sp . SF-1917, have been isolated by column chromatography on Diaion HP-20 and silica gel . Physico-chemical properties suggested that they are disaccharide nucleosides . Dapiramicin A underwent epimerization, under acidic condition, into epidapiramicin A . Although dapiramicin A generally exhibits no in vitro activity, it is very effective against the sheath blight of rice plants caused by Rhizoctonia solani in a green house test. Arzneimittelforschung, 1984, 34(11), 1540 - 2 Effects of dibekacin, a new aminoglycoside antibiotic, on the rat sciatic nerve-gastrocnemius muscle preparation; Renna G et al.; O-3-amino-3-deoxy-alpha-D-glucopyranosyl-(1----6)-O-{2,6-diamino-2,3,4,6 -tetradeoxy-alpha-D-erythro-hexopyrano-hexopyranosyl-(1----4 ) }-2-deoxy-L- streptamine (dibekacin), like other known aminoglycoside antibiotics, possesses a dose-dependent neuromuscular blocking activity in vivo . d-Tubocurarine, at a dose which per se does not influence the contraction of gastrocnemius muscle elicited by sciatic nerve stimulation, significantly potentiates the neuromuscular blockade produced by dibekacin . Neostigmine methylsulfate is unable to reverse the neuromuscular blocking activity of dibekacin, whereas calcium chloride antagonizes the neuromuscular blockade produced by this antibiotic. J Infect Dis, 1984 Jan, 149(1), 16 - 22 Lack of cross-reactivity between aztreonam , a monobactam antibiotic, and penicillin in penicillin-allergic subjects; Saxon A et al.; Monobactam antibiotics are a new class of beta-lactam antibiotics . In contrast to penicillins or cephalosporins, monobactams possess a monocyclic beta-lactam structure . IgE or immediate hypersensitivity cross-reactivity between aztreonam (a monobactam) and penicillin was investigated, since this will be an important consideration when therapy is chosen . The maximum concentration of aztreonam reagents not giving false-positive skin tests was determined in normal subjects who were not allergic to penicillin . Subsequently, 41 subjects with IgE antibody to one or more penicillin moieties, as determined by positive skin reactions, were tested with the aztreonam reagents . Thirty-seven of these persons showed no reactivity while four showed equivocal tests . Repeat tests in those four persons were negative to the aztreonam reagents, while their penicillin tests remained unchanged . These in vivo data suggest that there is no cross-reactivity between IgE antibodies to penicillin and aztreonam and provide a basis for investigating the therapeutic use of monobactams in patients who are allergic to penicillin. Brain Dev, 1984, 6(6), 566 - 70 Fibroblasts from patients with myotonic muscular dystrophy: cholesterol requirement for proliferation and sensitivity to polyene antibiotics; Ohno K et al.; The genetic defect in myotonic muscular dystrophy (MMD) remains obscure . From the evidence that drugs blocking cholesterol biosynthesis induce myotonia and increased serum concentrations of deoxycholic acids are common among patients with MMD, evidence of the abnormal sterol metabolism in MMD fibroblasts was sought by comparing them with fibroblasts from control individuals and patients with Duchenne muscular dystrophy (DMD) . Although early-onset type MMD and DMD fibroblasts have lower maximal cell densities than fibroblasts from age-matched control individuals do in medium containing 10% fetal bovine serum, we could not reveal any abnormalities in exogeneous cholesterol requirements for proliferation of MMD fibroblasts . This suggests that the sterol biosynthetic pathway in MMD fibroblasts is grossly intact . Furthermore, no difference were observed in sensitivities to polyene antibiotics, which bind to membrane sterols and presumably damage the cell membrane. Acta Med Scand, 1984, 216(5), 531 - 4 Leucopenia associated with beta-lactam antibiotic therapy; Kaaja R et al.; Two cases of penicillin-induced and one case of cephalosporin-induced leucopenia are described . This unusual complication of widely used beta-lactam antibiotics can occur when these antibiotics are administered parenterally in high doses for prolonged periods (14 days or more) . The close monitoring of the white cell count is important when treating patients with high doses of beta-lactam antibiotics for prolonged periods . We would like to emphasize that when penicillin- or cephalosporin-induced leucopenia is suspected, continuation with another beta-lactam antibiotic may be dangerous. Auris Nasus Larynx, 1984, 11(2), 53 - 60 Relationship between ototoxicity of aminoglycoside antibiotics and their transferability into inner ear fluids; Ohtani I et al.; The purpose of this study is to clarify the question whether the difference of severity of ototoxicity induced by the aminoglycoside antibiotics depends on the difference of quantity of transferability into inner ear . Aminoglycoside antibiotics (tobramycin, kanamycin, netilmicin and ribostamycin) were injected for 30 consecutive days to rabbits . The relationship between the severity of hair cell damage and concentration of antibiotics in perilymph was investigated . The drug concentration in the perilymph was determined by the bioassay method, and using the surface preparation technique the hair cell damage was observed under a phase contrast microscope . It was concluded that the difference of severity of ototoxicity induced by the aminoglycoside antibiotics is due to the difference of their own toxicity to hair cells but not to the difference of their transferability into the perilymph. Chemotherapy, 1984, 30(2), 88 - 91 Enhanced Escherichia coli susceptibility to nitrofurantoin by EDTA and multiple aminoglycoside antibiotics resistance mutation; Obaseiki-Ebor EE; Subinhibitory concentrations of ethylenediaminetetraacetic acid (EDTA) increased the susceptibility of Escherichia coli K12 multiple aminoglycoside antibiotics and nitrofurantoin-resistant mutants to aminoglycoside antibiotics (20- to 25-fold) and nitrofurantoin (15-fold) . The same concentration of EDTA also increased the susceptibility of high-level nitrofurantoin-resistant mutants to nitrofurantoin . Aminoglycoside-resistant mutants with increased susceptibility to nitrofurantoin (2- to 3-fold) were selected with neomycin from E . coli nitrofurantoin-sensitive and resistant mutants . Decreased permeability of nitrofurantoin is inferred as one of the mechanisms of nitrofurantoin resistance. J Exp Pathol, 1984 Fall, 1(4), 307 - 13 Use of plasmid-mediated resistance to the antibiotic G418 for the rapid screening of a yeast mutant library; Chenevert JM et al.; Both haploid and diploid yeast cells are sensitive to the antibiotic G418 . The former develop spontaneous resistance to G418 at a frequency of approximately 2 X 10(-6), however, the frequency of resistance in diploids is less than 1 X 10(-9) and was undetectable in these experiments . Mating of spontaneously resistant haploid cells to G418-sensitive strains yields sensitive diploids, indicating that spontaneous resistance to the antibiotic is a recessive trait . Both haploid and diploid cells can be efficiently transformed to G418 resistance by a plasmid carrying the Escherichia coli kanamycin resistance (kanr) marker . The ability to select for cells transformed with plasmids containing the kanr gene has facilitated the screening of a large series of temperature sensitive yeast mutants to determine whether any of them are allelic to RAD3. Acta Chir Scand, 1984, 150(8), 689 - 92 Incision and drainage v . incision, curettage and suture under antibiotic cover in anorectal abscess . A randomized study with 3-year follow-up; Kronborg O et al.; Conventional incision and drainage was compared with incision plus curettage and primary suture of abscess cavity under antibiotic cover in a prospective, randomized trial of 83 patients with acute anorectal abscess with or without low fistula . All the patients were followed up for three years . The time to healing was on average three weeks less after suture than after incision alone . The difference was statistically significant . Primary healing was obtained in 32 of 42 cases after suture . Recurrence of abscess tended to be more frequent after suture, but the time to healing of initial and recurrent abscesses and fistulas in the three-year observation period continued to be three weeks less after suture than after incision alone, making suture the most attractive treatment. Nucleic Acids Symp Ser, 1984, (15), 65 - 7 Structure and biological activity of ascamycin, a new nucleoside antibiotic; Isono K et al.; A newly isolated strain of Streptomyces sp . produces a new nucleoside antibiotic, ascamycin and the corresponding dealanyl derivative . The structure of ascamycin was determined to be 2-chloro-9-beta-{5-O-(N-L-alanyl)sulfamoyl-D-ribofuranosyl}-adenine . Remarkable selective toxicity of ascamycin compared to the dealanyl derivative was accounted for on the basis of a dealanylating enzyme present in the envelope of sensitive bacteria . After dealanylation, it becomes permeable to cell membrane. Res Vet Sci, 1984 Jan, 36(1), 5 - 11 Small filter membrane bags for the study of antibiotic action in the digestive tract: bioavailability and in situ activity of oxytetracycline, chloramphenicol, neomycin and gentamicin in the pig caecum; Escoula L et al.; Observations were made for two consecutive days on the disposition of oxytetracycline, chloramphenicol, neomycin and gentamicin through the digestive tract of pigs given an oral drench . The effect of these antibiotics upon the colibacilli flora and upon an Escherichia coli 127 strain in small filter membrane bags placed into the caecum was also investigated . For chloramphenicol, inactivation by antibiotic resistant colibacilli and, for neomycin, losses of activity by digestive content may explain the lower concentrations obtained in the gut and the correlative lack of curative or preventive action against E coli 127 in small bags . Tetracycline and gentamicin prevented growth of E coli 127 from the second day. Probl Endokrinol (Mosk), 1984 Jan-Feb, 30(1), 57 - 61 {Biosynthesis and secretion of insulin under the effect of an antibiotic of the tetracycline group}; Poltorak VV; Formation and secretion of insulin during administration of tetracycline hydrochloride in vivo and in vitro were studied in experimental rat Langerhans islets isolated by enzymatic digestion with collagenase . Insulin secretion was determined by radioimmunoassay, insulin biosynthesis was assessed from 3H-leucin incorporation into the de novo formed proteins of the islets with insulin immunoreactivity (proinsulin plus insulin) . Injection of the antibiotic in a dose of 25 mg/kg intraperitoneally for 10 days did not change the functional activity of beta-cells--the rate of insulin formation and secretion at low and high glucose concentrations in the incubation medium . Higher doses of the antibiotic applied in vivo (100 mg/kg intraperitoneally for 10 days) and in vitro (100 mumol, 2-hour incubation) inhibited the glucose-stimulated (15 mmol) insulin secretion but exerted no effect on insulin biosynthesis . The possible importance of ionophore properties of the antibiotic, that changes the concentration of intracellular Ca2+ in the mechanism of dissociated action of tetracycline hydrochloride on insulin formation and secretion, as well as the practical significance of the data obtained a