Biochemistry, 1986 Mar 25, 25(6), 1249 - 58 DNA sequence specificity of the pyrrolo{1,4}benzodiazepine antitumor antibiotics . Methidiumpropyl-EDTA-iron(II) footprinting analysis of DNA binding sites for anthramycin and related drugs; Hertzberg RP et al.; Anthramycin, tomaymycin, and sibiromycin are members of the pyrrolo{1,4}benzodiazepine {P(1,4)B} antitumor antibiotic group . These drugs bind covalently through N2 of guanine and lie within the minor groove of DNA {Petrusek, R . L., Anderson, G . L., Garner, T . F., Fannin, Q . L., Kaplan, D . J., Zimmer, S . G., & Hurley, L . H . (1981) Biochemistry 20, 1111-1119} . The DNA sequence specificity of the P(1,4)B antibiotics has been determined by a footprinting method using methidiumpropyl-EDTA-iron(II) {MPE.Fe(II)}, and the results show that each of the drugs has a two to three base pair sequence specificity that includes the covalently modified guanine residue . While 5'PuGPu is the most preferred binding sequence for the P(1,4)Bs, 5'PyGPy is the least preferred sequence . Footprinting analysis by MPE.Fe(II) reveals a minimum of a three to four base pair footprint size for each of the drugs on DNA with a larger than expected offset (two to three base pairs) on opposite strands to that observed in previous analyses of noncovalently bound small molecules . There is an extremely large enhancement of MPE.Fe(II) cleavage between drug binding sites in AT rich regions, probably indicating a drug-induced change in the conformational features of DNA which encourages interaction with MPE.Fe(II) . In the presence of sibiromycin or tomaymycin the normally guanine-specific methylene blue reaction used in Maxam and Gilbert sequencing cleaves at other bases in defined positions relative to the drug binding sites . Finally, modeling studies are used to rationalize the differences and similarities in sequence specificities between the various drugs in the P(1,4)B group and their reactions with DNA. Gan To Kagaku Ryoho, 1986 Mar, 13(3 Pt 2), 697 - 700 {Immunomodulation by antitumor antibiotics}; Ishizuka M; Antibiotics exhibiting immunomodulatory activities were found among antitumor antibiotics . These antibiotics had antileukemic activity . Neothramycin and mazethramycin, which are classified as anthramycin-group antibiotics, activated macrophages so that they became antitumor effector cells . Aclacinomycin and oxanosine inhibited generation of suppressor cells in tumor-bearing mice and oxanosine enhanced antitumor effector cells . Therapy using spergualin produced specific antitumor immunity in cured mice . The immunomodulatory activities of auromomycin and bactobolin were also reported. Mol Pharmacol, 1986 Mar, 29(3), 293 - 8 Effect of the polar head structure of polyene macrolide antifungal antibiotics on the mode of permeabilization of ergosterol- and cholesterol-containing lipidic vesicles studied by 31P-NMR; Cybulska B et al.; Natural polyene macrolide antibiotics and their N-acyl and methyl ester derivatives, which differ mainly in their electric net charge, were compared for their ability to increase the ionic permeability of large unilamella vesicles, using the proton-cation exchange method and 31P-NMR spectroscopy . The zwitterionic (amphotericin B, vacidin A) and negatively charged (N-N'-diacetyl vacidin) compounds induced permeability according to an all-or-none process on both cholesterol- and ergosterol-containing membranes . The same mechanism of permeability induction is obtained only on ergosterol-containing vesicles for positively charged antibiotics (perimycin A, vacidin A methyl ester, amphotericin B methyl ester) . A different type of action is observed for the latter group of ionophores in cholesterol-containing vesicles . In this case, a progressive proton efflux occurs in which all of the vesicle population is involved . This qualitative difference in the kinetics of ionic fluxes induced by antibiotics without a free carboxyl group in cholesterol-containing as compared to ergosterol-containing membranes was ascribed to differences in polyene-sterol interactions as well as in the life time of the ionic path formed . This difference may provide a basis for the improvement of selective toxicity of this group of antifungal agents by rational modifications. J Antibiot (Tokyo), 1986 Mar, 39(3), 424 - 9 Studies on macrocyclic lactone antibiotics . VIII . Absolute structures of rhizoxin and a related compound; Iwasaki S et al.; The absolute structure of rhizoxin, a potent antifungal and antitumor antibiotic, was determined by interrelation with compound 2 whose structure was established by X-ray analysis . Since a 18OH group was introduced at C-3 on a hydrolytic cleavage of C-2, C-3 epoxy group with alkaline H2(18)O, the original epoxy oxygen should be retained at C-2 . The stereo-chemistry at C-2 and C-3 positions in rhizoxin was, therefore, determined as 2R,3S. Jpn J Antibiot, 1986 Mar, 39(3), 693 - 700 {Disulfiram-like reactions resulting from the administration of cephem antibiotics with methyltetrazolethiol moiety examined by using different doses}; Nakahata H et al.; The disulfiram-like reactions following the treatment of cephem antibiotics with methyltetrazolethiol moiety (latamoxef (LMOX) and cefoperazone (CPZ) was studied by using large (500 mg/kg) and small (50 mg/kg) doses of the drugs . Normal and fatty liver rats were injected intraperitoneally with the cephem antibiotics . After overnight fasting blood samples were obtained following an administration of 20% ethanol (2g/kg) . Blood ethanol and acetaldehyde concentrations, and liver acetaldehyde dehydrogenase activity were determined . Blood ethanol concentration upon the small dose was similar to that obtained upon the large dose in both groups of normal and fatty liver rats . Blood acetaldehyde concentration upon the large dose was higher than that upon the small dose; 2-fold increase in normal rats and 2.6-4.7-fold increase in fatty liver rats were observed after administering LMOX, while 3.7-fold increase in normal rats and 5-5.7-fold increase in fatty liver rats upon administering CPZ . Additionally, liver acetaldehyde dehydrogenase activity (Enzyme 1) observed upon the large dose was lower than that observed upon the small dose; the degree of reduction was 33% in normal and 19% in fatty liver rats upon the administration of LMOX, while 37% in normal and 45% in fatty liver rats upon the administration of CPZ. J Chir (Paris), 1986 Mar, 123(3), 207 - 8 {Value of ceftriaxone (Rocephine) within the framework of preventive antibiotic therapy in digestive surgery}; Zeyer B et al.; The authors report their experience with prophylactic antibiotic therapy by Ceftriaxone in 30 cases of digestive surgery, the advantage of this new 3rd generation cephalosporin is that only one injection every 24 hours is quite efficient. Antibiot Med Biotekhnol, 1986 Mar, 31(3), 181 - 4 {X-ray structural study of the pyrimido-{5,4-e}-1,2,4-triazine antibiotics xanthothricin and fervenulin}; Aleksandrov GG et al.; The structures of xanthothricin (I) and fervenulin (II), pyrimido-{5,4-e}-1,2,4-triazine antibiotics were determined by x-ray analysis . The crystals of I and II are monoclinic: a 9.667(6), 18.270(7), b 14.029(9), 5.723(2), c 6.914(3), 18.058(7) A, beta 116.47(3), 118.90(2) degrees, Z 4,8; space group P21/c . Analysis of bond length distribution in I and II was indicative of significant alternation of the double and ordinary bonds. Farmakol Toksikol, 1986 Mar-Apr, 49(2), 11 - 3 {Effect of antibiotics on D-serotonin-reactive structures}; Efimova TE et al.; Experiments on the isolated organs showed that ampicillin and levomycetin have pronounced D-antiserotoninergic effects; antagonism of antibodies and serotonin was found to be of competitive type . At an increase in levomycetin dosage D-antiserotoninergic effect was followed by the spasmolytic effect . Kefzol and benzylpenicillin failed to show any D-antiserotonin-ergic properties. Can J Microbiol, 1986 Mar, 32(3), 268 - 72 Manganese and antibiotic biosynthesis . II . Cellular levels of manganese during the transition to patulin production in Penicillium urticae; Scott RE et al.; The radionuclide 54MnCl2 was used to examine the cellular manganese content of submerged cultures of Penicillium urticae NRRL 2159A . Liquid-scintillation spectroscopy allowed sensitive detection of isotopic manganese in both normally supplemented and manganese-deficient cultures . The cellular manganese content in supplemented cultures showed three distinct phases, including a period of uptake that coincided with the time of transition to antibiotic biosynthesis . Such an uptake was not seen for manganese-deficient cultures, but addition of normal quantities of unlabelled manganese to the media appeared to stimulate uptake . Preliminary characterization shows this manganese uptake is not inhibited by other metal ions, does not require metabolic energy or a protein component, but is disrupted by changes in incubation temperature . The significance of these observations is discussed in the light of recent work on the requirement for manganese for antibiotic biosynthesis in this organism. Can J Microbiol, 1986 Mar, 32(3), 259 - 67 Manganese and antibiotic biosynthesis . I . A specific manganese requirement for patulin production in Penicillium urticae; Scott RE et al.; The effect of trace metal nutrition on the functioning of the patulin biosynthetic pathway in submerged cultures of Penicillium urticae (NRRL 2159A) was examined by both chromatographic and enzymological means . Comprehensive metal ion analysis showed generally low levels of contaminating metal ions in media components . Of eight metal ions examined, only manganese strongly influenced secondary metabolite production . In control cultures or cultures deficient in calcium, iron, cobalt, copper, zinc, or molybdenum, pathway metabolites appeared in the medium at about 25 h after inoculation . The first pathway-specific metabolite, 6-methylsalicylic acid, accumulated only transiently before being converted to patulin whose concentration steadily increased . In manganese-deficient cultures, however, 6-methylsalicylic acid continued to accumulate, with only minor amounts of patulin being produced . Additionally, a marker enzyme for the pathway showed only 0-20% of control activity . Clear dose responses (patulin versus manganese) were found in different media, with no effect on growth yield . Addition of manganese to depleted cultures at 18, 26, or 36 h resulted in increasing marker enzyme activity and patulin concentrations . It is concluded that manganese exerts a specific, positive effect on patulin biosynthesis and may in some way control the section of the patulin pathway occurring after 6-methylsalicylic acid. Agents Actions, 1986 Mar, 17(5-6), 449 - 53 De novo generation of histamine in sputum and the effect of antibiotics; Sheinman BD et al.; We have performed experiments to test the hypothesis that bacteria may contribute to the presence of histamine in sputum . Sputum samples obtained from 7 patients with exacerbations of chronic bronchitis and 7 patients with cystic fibrosis were incubated at 37 degrees C for 72 hours . Serial sputum histamine estimations, performed by a recently-developed HPLC technique, showed large, progressive increases in both groups of samples . Both the pre-heating of samples at 100 degrees C prior to incubation and the addition of antibiotics to the incubates substantially reduced these increases . These findings strongly suggest that bacteria may contribute to sputum histamine in infective lung disease. J Anim Sci, 1986 Mar, 62(3), 844 - 56 Effects of dietary nitrogen level and ileal antibiotic administration on digestion and passage rate in beef heifers . II . High-forage diets; Goetsch AL et al.; Four beef heifers (258 kg), fitted with ruminal, duodenal and ileal cannulae (T-type), were fed a high-forage diet with a low (L) or high (H) level of N (1.44 and 2%, respectively), and received daily doses of either antibiotics (A; 2 g neomycin sulfate and .25 g of bacitracin) or saline (S) into the ileum in a 4 X 4 Latin-square experiment . Passage of nonammonia-N to the duodenum represented 128, 142, 92 and 104% of N intake for LS, LA, HS and HA treatments, respectively, indicating that administration of antibiotics into the ileum tended to increase the output of N from the rumen . Digestion of organic matter, acid detergent fiber and starch in the rumen tended to be lower in animals receiving antibiotics in the terminal ileum . Administration of antibiotics into the ileum tended to increase ruminal ammonia-N (NH3-N) concentration with the H diet, but to decrease ruminal NH3-N with the L diet . Particle passage rate from the rumen, estimated from marker concentrations in feces, was negatively related to ruminal organic matter digestion (r = -.52; P less than .03) . Ileal antibiotic infusion tended to slow passage of fluid from the rumen and hindgut, but to increase volume of digesta in the hindgut. Int J Clin Pharmacol Ther Toxicol, 1986 Mar, 24(3), 130 - 8 Effects of aminoglycoside antibiotics on the neuromuscular junction: Part I; Yamada S et al.; The effects of aminoglycoside antibiotics (AGA) including streptomycin (SM), kanamycin (KM), gentamicin (GM), dibekacin (DKB), amikacin (AMK) and sisomycin (SISO), on the neuromuscular junction were studied by in vivo and in vitro experiments . In in vitro experiments, no effect of AGA on rat phrenic nerve diaphragm preparations was observed, but the use of the antibiotics at a high concentration exerted a slight blocking effect on the neuromuscular junction . The blocking effect of SISO and DKB on the neuromuscular junction was marked . These antibiotics were definitely found to compete with eserine in terms of the blocking effect on the neuromuscular junction, but did not compete with calcium chloride . In in vitro experiments with frog sciatic nerve and musculus sartorius preparations, DKB and SISO exerted a blocking effect on the NMJ, inducing the disappearance of action potentials and the appearance of endplate potentials (EPPs) . In in vitro experiments with the preparations from Rana catesbiana frogs, SM, GM, DKB and SISO exhibited an inhibiting effect on the release of acetylcholine (ACh), a chemical neurotransmitter in neuromuscular junction, resulting in a decrease in the frequency of miniature endplate potentials (mEPPS) . In in vivo experiments with rabbit sciatic tibialis anterior muscle preparations, SM, GM, DKB and SISO exerted a blocking effect on the neuromuscular junction . From the facts that the effect was augmented by the use of magnesium chloride combined with these antibiotics and that the antibiotics competed with calcium chloride and potassium chloride in terms of the blocking effect on the neuromuscular junction, the effects seemed to be due to the inhibition of ACh release.(ABSTRACT TRUNCATED AT 250 WORDS) Infect Control, 1986 Mar, 7(3), 168 - 71 All-inclusive concurrent antibiotic usage review: a way to reduce misuse without formal controls; Heineman HS et al.; During an 11-week period, all antibiotic usage on a 113-bed medical teaching service was reviewed concurrently in weekly sessions between house staff and a review team . Recommendations for change, based on accepted criteria, were communicated by the house officer to the attending physician . In one-half of the patients no change was suggested; in one-third, a recommended change was made; and in only one-sixth was a recommendation not followed . Cost savings were conservatively estimated to approach $10,000 in this pilot study; this extrapolates to almost $300,000 per year for the 714-bed medical center, or more than 18% of the antibiotic expenditures . This program achieves its objective in a nonthreatening, noncontrolling manner, provides continuing education, and contributes to improved patient care. Can J Microbiol, 1986 Mar, 32(3), 273 - 9 Manganese and antibiotic biosynthesis . III . The site of manganese control of patulin production in Penicillium urticae; Scott RE et al.; Although manganese had been shown to be an essential requirement for patulin biosynthesis, its site of action was unknown . Four possibilities were considered . A manganese requirement for the second pathway enzyme, a decarboxylase, was discounted since mid and late pathway intermediates were not converted to patulin in manganese-deficient cultures . A major disruption in primary metabolism and hence secondary metabolism was discounted since eight primary metabolism enzymes showed no evidence of unusual changes in specific activity when normal and manganese-deficient cultures were compared . Inhibitor studies using actinomycin D and cycloheximide showed that there was no activation of preexisting enzyme proteins and that manganese did not influence translation . The inhibitor studies did show, however, that manganese exercised its effect on patulin biosynthesis by influencing the coordinate appearance of pathway enzymes though an effect at the level of transcription. J Antimicrob Chemother, 1986 Mar, 17(3), 269 - 79 Suggested mechanisms for the antimycotic activity of the polyene antibiotics and the N-substituted imidazoles; Thomas AH; The polyene antibiotics and the N-substituted imidazoles (azoles) are two groups of clinically important antifungal drugs . Both are hydrophobic and both interact with the plasma membrane of susceptible fungi but the mode of action of the two groups is not fully resolved . In this paper their biological properties are reviewed in the context of recent work so that common features may be identified and further areas of research indicated. J Clin Oncol, 1986 Mar, 4(3), 346 - 52 Reporting the results of randomized trials of empiric antibiotics in febrile neutropenic patients--a critical survey; Pater JL et al.; Twenty-one randomized trials of empiric antibiotic therapy in febrile neutropenic patients were reviewed and scored by methods suggested by Chalmers . In general, the scores were low, indicating that many of these articles failed to meet currently suggested methodologic standards for publication of results of clinical trials . Particularly striking was the lack of attention paid to statistical issues, such as power, exclusions, and repeated analyses . In addition, there appears to be a need for a better-developed system for assessing response in these circumstances. Jpn J Antibiot, 1986 Mar, 39(3), 751 - 60 {Clinical studies on the transference of cephem-type antibiotics into bile and gallbladder tissues with special reference to cefotiam and cefmenoxime}; Shiozaki H et al.; Cefotiam (CTM) and cefmenoxime (CMX) were studied for their serum concentrations and transference into bile in patients with PTCD or T-tube . One gram of CTM or either 1 g or 2 g of CMX was administered by an intravenous drip infusion for over 30 minutes . These drugs were also studied for their serum concentrations, bile concentrations, and tissue concentrations in the walls of the gallbladder of patients operated on for cholelithiasis . Intravenous drip infusion (over 30 minutes) was used to administer 1 g of CTM or 1 g or 2 g CMX immediately before surgery . Both CTM and CMX were readily transferred into bile . Their bile concentrations, however, varied greatly among patients, and extremely low levels were detected in some patients . A crossover analysis of concentrations of CMX in bile of patients given doses of 1 g and 2 g revealed a dose-response relationship . The crossover analysis of drug concentrations in bile of patients given CTM and CMX showed that CMX is transferred more readily to bile . The relationship between liver functions and drug transfer to bile was examined by plotting the total bilirubin level against drug concentrations in bile . The plots formed an exponential curve with a correlation coefficient (r) being -0.52 in cases when each subjects received 1 g of CTM and -0.72 in cases when each subjects received 1 g of CMX . A study of 3 patients given CMX at a dose of 1 g suggested that bile levels of CMX may be correlated to ICG . Concentrations of CTM and CMX in tissues of the gallbladder wall were fairly high, with unexpectedly small variance among patients . Even in patients with low bile concentrations of these drugs, drug levels in the tissues of the gallbladder wall were high . Drug levels in the noninflammatory tissues were higher than those in inflammatory lesions . The above findings suggest that CTM should be the antibiotic of choice for patients with ordinary biliary tract infections and after the surgery of the liver and biliary tract system, while CMX should be the antibiotic of choice for patients with severe biliary tract infections, and for compromised hosts after the surgery of the liver and biliary tract system. Biull Eksp Biol Med, 1986 Mar, 101(3), 302 - 4 {Prostaglandin synthetase activity in the different layers of the kidneys of young rats exposed to polyene antibiotics}; Efendiev AM et al.; Prostaglandin (PG)-synthestase activity was studied in the cortical, medullary and papillary kidney layers in young rats subjected to prolonged administration of polyene antibiotics (amphotericin B, levorin and nystatin) . This activity was markedly increased during the first few hours after the administration of amphotericin B . At later terms a pronounced decline in the enzyme activity was observed . The changes were most prominent in the medullary and papillary layers . The other two antibiotics were less potent . The experimental results have shown that amphotericin B had maximal effect on renal PG-synthetase activity, while the sodium salt of nystatin was least effective. Cancer Res, 1986 Mar, 46(3), 1073 - 8 In vitro effects of an antitumor antibiotic, ascofuranone, on the murine immune system; Magae J et al.; Effects of an antitumor antibiotic, ascofuranone (AF) on the murine immune system were studied . Unlike lectins, AF did not induce any proliferative response of splenocytes . Furthermore, AF significantly inhibited proliferative response of splenocytes in response to lectins, such as concanavalin A, lipopolysaccharide, or phytohemagglutinin above 5 micrograms/ml . In concanavalin A-induced T-lymphocyte response, AF selectively inhibited the formation of interleukin 2 (IL-2) receptors, which was observed above 0.4 micrograms/ml . On the other hand, the inhibitory effect on the proliferative response to IL-2 of T-lymphocytes, which had already obtained IL-2 receptors, was observed above 10 micrograms/ml . IL-2 production of splenocytes in response to concanavalin A was also suppressed by AF above 2 micrograms/ml and only 3% of IL-2 was produced in the presence of AF, 10 micrograms/ml . However, AF-activated macrophages and their glycolysis was significantly stimulated . Activation of macrophages by AF was also confirmed by stimulation of interleukin 1 production and tumoricidal activity . However, natural killer activity of splenocytes was suppressed at the concentration where significant activation of tumoricidal activity of macrophages was observed . Therefore, AF had a dual effect on the immune system . Macrophages were activated to produce interleukin 1 and to kill tumor cells . On the other hand, functions of lymphocytes were suppressed. Antimicrob Agents Chemother, 1986 Mar, 29(3), 451 - 5 Lysis of nongrowing Escherichia coli by combinations of beta-lactam antibiotics and inhibitors of ribosome function; Kusser W et al.; It is generally assumed that only actively growing bacteria are killed by inhibitors of peptidoglycan synthesis . Several exceptional examples are described here . As expected, ampicillin did not lyse nongrowing, amino acid-deprived cultures of relA+ strains of Escherichia coli, but the subsequent addition of several ribosome inhibitors (chloramphenicol, tetracycline, gentamicin, and kanamycin) caused various degrees of lysis in such ampicillin-treated cultures . Of the antibiotics tested, only streptomycin was ineffective in this regard . Peptidoglycan synthesis has been shown to be inhibited in amino acid-deprived relA+ bacteria by the stringent control mechanism (E . E . Ishiguro and W . D . Ramey, J . Bacteriol . 127:1119-1126, 1976), and the ribosome inhibitors tested here relaxed peptidoglycan synthesis to various degrees under these conditions . The relative lysis-inducing activities of the ribosome inhibitors on ampicillin-treated, amino acid-deprived bacteria were directly correlated to their relative activities as stringent control antagonists . This phenomenon was not dependent on amino acid deprivation . Cultures treated with growth inhibitory levels of the various ribosome inhibitors alone were lysed by ampicillin, apparently because peptidoglycan synthesis continues uninhibited when growth is arrested by treatment with ribosome inhibitors . These results indicate that autolysis can be triggered by the inhibition of peptidoglycan synthesis occurring in the absence of wall expansion; i.e., active cell growth is unnecessary. J Chromatogr, 1986 Feb 28, 354, 317 - 24 Separation of aromatic heptaene antibiotics by high-performance liquid chromatography; Thomas AH et al.; Thin-layer chromatography and high-performance liquid chromatography have been used to separate and characterize representatives of the aromatic heptaene group of antifungal antibiotics . Most antibiotics were complex mixtures that could be placed in well defined groups . The identity of candicidin and levorin was confirmed in one group . Aureofungin, DJ400 and hamycin shared many components in common in the second group . The proportion of the individual components of lucknomycin and trichomycin was markedly different from each other and from the antibiotics in the other two groups . Lucknomycin stood out as the most homogeneous of the antibiotics examined. CMAJ, 1986 Feb 15, 134(4), 357 - 9 Inappropriate use of antibiotics in croup at three types of hospital; Pianosi P et al.; Despite recent suggestions that bacterial infection is an increasingly important cause of serious croup, most authorities still consider croup a viral disease in which antibiotic therapy is unnecessary . To assess the frequency of antibiotic use in croup among children in hospital, we reviewed the records at three types of hospital in Ontario . Children with evidence of a concurrent infection that might be bacterial were considered to have received antibiotics appropriately . Whereas only 6% of cases at a university-affiliated children's hospital were inappropriately treated with antibiotics, the proportions at a small rural community hospital staffed by general practitioners and a general hospital staffed by both pediatricians and general practitioners in a medium-sized city were 63% and 38% . Possible reasons for these differences are discussed. J Antibiot (Tokyo), 1986 Feb, 39(2), 266 - 71 Regulation of enzymes involved in the biosynthesis of the sesquiterpene antibiotic pentalenolactone in Streptomyces arenae; Maurer KH et al.; The production of the sesquiterpenoid antibiotic pentalenolactone in the producer strain Streptomyces arenae TU 469 is controlled by the activity of the enzyme farnesylpyrophosphate cyclase . In contrast to the activity of this enzyme, the specific activities of all other enzymes of the mevalonoid pathway tested so far, proved to be not rate-limiting . Several metabolites of the pentalenolactone pathway were tested for inhibitory effects on the activity of the HMG-CoA reductase and farnesylpyrophosphate cyclase . The activity of the cyclase was inhibited by low concentrations of pentalenolactone and its derivatives, thus suggesting an end product inhibition of the starting enzyme of the pentalenolactone pathway . The activity of HMG-CoA reductase was not inhibited by pentalenene or any pentalenolactone-derivatives . According to these results, an end-product inhibition of the first enzyme which is specific for pentalenolactone synthesis seems to be a mechanism involved in the regulation of pentalenolactone biosynthesis. Chemioterapia, 1986 Feb, 5(1), 33 - 6 Short-term antibiotic therapy with clindamycin phosphate in patients with malignant epithelial tumors: an immunological evaluation; Cerra R et al.; The authors evaluated the results of a study using clindamycin phosphate plus gentamicin in short-term therapy in patients with tumors submitted to surgery for removal of the primary lesion . Only 6.6% of these patients became infected, and these good results are most likely due to the synergic activity of clindamycin with the physiological immune response . This agent, in fact, was able to interfere with IgM/IgA immunoregulatory balance by enhancing IgM production and, consequently, phagocytic mechanisms. J Med Microbiol, 1986 Feb, 21(1), 39 - 42 Characterisation and antibiotic susceptibilities of Streptobacillus moniliformis; Edwards R et al.; The characteristics of seven strains of Streptobacillus moniliformis, including four isolates from a recent outbreak of Haverhill fever, are reported . Acid production from carbohydrates was uniform apart from variable reactions with mannose and salicin . Enzymatic reactions determined by the API ZYM system and fatty-acid profiles were generally consistent and may be of value in the rapid identification of S . moniliformis . Penicillin was the most active of the antibiotics tested in vitro, which supports its use as the drug of choice in the treatment of Haverhill fever. Drug Intell Clin Pharm, 1986 Feb, 20(2), 134 - 7 Reducing prophylactic antibiotic costs in cardiovascular surgery: the role of the clinical pharmacist; Peterson CD et al.; A project was undertaken to demonstrate significant drug cost savings from clinical pharmacy services . The method of identifying and documenting the problem and the presentation and implementation of the project are discussed . The cost savings of the project are presented, including the economic impact on the patient and institution . The clinical pharmacist, the key figure in the success of the project, presented a complete pharmacological and financial analysis of the project to the medical staff . The project resulted in a financial savings of approximately $600 000/yr to patients in decreased drug charges, $200 000/yr in decreased drug purchases/inventory, and $105 000/yr to the hospital in an improved revenue/expense statement . This project represents an example of the important role of the clinical pharmacist in helping a hospital identify areas to reduce drug therapy costs . A future role for clinical pharmacists will be to work closely with the director of pharmacy, hospital administration, and medical staff in identifying and implementing cost-effective drug therapy. Am J Surg, 1986 Feb, 151(2), 205 - 8 Blood-pancreatic juice barrier to antibiotic excretion; Burns GP et al.; Antibiotics were given intravenously to dogs with chronic pancreatic fistulas, and serum and pancreatic juice levels were measured . Despite adequate serum values, gentamicin, tetracycline, clindamycin, and moxalactam did not appear in the pancreatic juice, which suggested a barrier to their excretion . In contrast, chloramphenicol reached a peak concentration in the pancreatic juice that amounted to 36 percent of the peak serum value . In the pancreatic juice, ampicillin, cefoxitin, and cefamandole reached only 5 percent of the peak serum values but were still within the therapeutic range . We have concluded that there is a blood-pancreatic juice barrier to some antibiotics, which leads to selective excretion. Am J Surg, 1986 Feb, 151(2), 200 - 4 Cost analysis of antibiotics in the management of perforated or gangrenous appendicitis; Gill MA et al.; Costs associated with treating patients for gangrenous or perforated appendicitis were compared . Patients received single agent therapy with cefoperazone or cefamandole or combination antibiotics consisting of clindamycin and serum level-adjusted gentamicin . Forty-eight patients received cefamandole, 47 received cefoperazone, and 52 received combination clindamycin and gentamicin . Costs to the pharmacy for drugs were greater for the combination therapy; however, the higher failure rate associated with the cephalosporins created greater expenses for the single agent therapy than for combination therapy. Antimicrob Agents Chemother, 1986 Feb, 29(2), 371 - 3 Ultrastructural changes in mollicutes induced by the peptide antibiotic herbicolin A; Birkelund S et al.; Electron microscopy of negatively stained mycoplasma, ureaplasma, and acholeplasma cells showed ultrastructural changes after 10 min of treatment of the organisms with the peptide antibiotic herbicolin A in concentrations ranging from 10 micrograms/ml for Mycoplasma capricolum to 600 micrograms/ml for Ureaplasma urealyticum . The morphological changes were shown to be reversible at low concentrations of the antibiotic but irreversible at high concentrations. Jpn J Antibiot, 1986 Feb, 39(2), 596 - 611 {Effect of (2"R)-4'-O-tetrahydropyranyladriamycin, a new antitumor antibiotic, on the bone marrow function of rabbits . (2) Repeated intravenous injections}; Tone H et al.; (2''R)-4'-O-Tetrahydropyranyladriamycin-HCl (THP), a new antitumor antibiotic, was intravenously injected to New Zealand White rabbits at a dose of 2.5 mg/kg every 2 weeks for 6 weeks (3 courses) or at a dose of 0.5 mg/kg/day daily for the first 5 days of a 2-week course for 6 weeks (3 courses) . The total dose was 7.5 mg/kg in both dosing schedules . The peripheral leucocyte and erythrocyte counts decreased . The leucocyte count decreased to 57% of the initial count on Day 3 in the first course and then increased gradually . The decrease was smaller in the divided dosing schedule than the single dosing . The nucleated cells, especially immatured myelocytes and erythroids reduced remarkably . Subsequently the matured myelocyte ratio in bone marrow cell constituents increased and the M/E ratio increased . These changes were observed on Day 3 and reverted by Day 9 in each course . The divided dosing schedule resulted in a higher nadir . All the changes in the peripheral blood and the bone marrow reverted even after the 3 course-treatment. Jpn J Antibiot, 1986 Feb, 39(2), 583 - 95 {Effect of (2"R)-4'-O-tetrahydropyranyladriamycin, a new antitumor antibiotic, on the bone marrow function of rabbits . (1) Intravenous administration by a single bolus injection}; Tone H et al.; New Zealand White rabbits were treated with (2"R)-4'-O-tetrahydropyranyladriamycin-HCl (THP), a new antitumor antibiotic, by an intravenous bolus injection at a dose of 1, 2 or 4 mg/kg . The peripheral leucocyte counts decreased markedly at doses of 2 and 4 mg/kg 1 to 7 days after injection, and the lymphocytes and neutrophils were affected . The nucleated cell count decreased in the bone marrow . Especially 3 days after injection, remarkable reductions of erythroids and immatured myelocytes were observed, with a subsequent rise of the matured myelocytes ratio in bone marrow cell constituents . These changes resulted in a marked increase of M/E ratio . Doxorubicin also showed an inhibitory effect on the bone marrow function of rabbits but the effect was slightly lower than THP . These changes of bone marrow cells reverted 7 days after injection and the recovery of the reduced peripheral leucocyte was also observed 14 days after injection . Therefore, it can be concluded that THP showed suppressive but reversible effects on the bone marrow function of rabbits. Jpn J Antibiot, 1986 Feb, 39(2), 569 - 81 Acute local irritative effect of (2''R)-4'-O-tetrahydropyranyladriamycin, a new antitumor antibiotic; Tone H et al.; (2"R)-4'-O-Tetrahydropyranyladriamycin hydrochloride (THP), a new antitumor antibiotic, was administered to rabbits at a concentration from 0.02 to 0.5% by instillation, or by intracutaneous, subcutaneous or intramuscular injection to study its local irritative effect . The irritative effect of THP increased with concentration . At a concentration of 0.5%, THP was irritant to the eye, skin and muscle but at a concentration of 0.1% practically no effect was observed . The effect was equal to or lower than that of doxorubicin . An instillation of 0.5% THP caused reversible irritation effect on the eye . Slight conjunctival responses (redness and chemoisis) were observed . Rinsing reduced the irritative effect . Intracutaneous injection of 0.1 ml of 0.5% THP caused well defined, moderate erythema, surface ulceration and dermal necrosis . Cutaneous muscle necrosis also occurred . At a concentration of 0.02%, dermal necrosis and inflammatory cell infiltration were observed . Erythema, as well as muscle necrosis and calcification with giant cell reaction and inflammatory cell infiltration were observed by an intramuscular injection at a concentration of 0.5% . Subcutaneous injection of 0.5% THP showed no irritative effect. Jpn J Antibiot, 1986 Feb, 39(2), 547 - 68 {Effect of (2"R)-4'-O-tetrahydropyranyladriamycin, a new antitumor antibiotic, on the cardiac function of hamsters}; Tone H et al.; Cardiovascular effects of (2''R)-4'-O-tetrahydropylanyladriamycin X HCl (THP) and doxorubicin (adriamycin, ADM) were studied in hamsters . In experiments to observe acute effects, THP was administered intravenously at a dose of 12.5, 25.0 or 50.0 mg/kg, and ADM at 1.56, 3.13 or 6.25 mg/kg was given to different subjects . The THP caused slight ECG alterations at a dose of 12.5 mg/kg . At a dose of 25.0 mg/kg or 50.0 mg/kg, THP caused moderate to remarkable alterations in ECG like a widening of PR and PRc interval, A-V block, ST segment depression and T wave flattening . The ADM caused moderate to remarkable alterations in ECG at a dose of 3.13 mg/kg or 6.25 mg/kg, including arrhythmia, bradycardia, A-V block, ST segment changes and T wave flattening . These changes caused by THP and ADM recovered within 5 approximately 10 minutes after injection . Alterations in the ultrastructure of the myocardium caused by THP at a dose of 50.0 mg/kg included some cells with slight changes like swelling of mitochondria, focal intracellular edema, and enlargement of myofibrils . The ADM, at a dose of 3.13 mg/kg, induced severer swelling of mitochondria than THP, dilatation of sarcoplasmic reticulum, intracellular edema, and disorganization of myofilaments . At a dose of 6.25 mg/kg of ADM, these changes became more pronounced . In experiments to observe subacute effects, hamsters were treated with THP or ADM by daily intraperitoneal injections for 15 consecutive days, and then allowed to be recovered for 15 days . Dose levels of THP or ADM were 0.125, 0.25, 0.5 and 1.0 mg/kg . General toxicity, ECG, hematological and blood biochemical analysis, and electron microscopic examination were studied . In the ECG study, THP-treated hamsters showed a reversible elevation of R wave amplitude at a daily dose of 0.5 mg/kg . Widening of PR and PRc interval, elevation of R and S wave amplitude, and reduction of T wave amplitude were observed at a daily dose of 1.0 mg/kg of THP . Hamsters treated with ADM showed increase of heart rate, reduction of T wave amplitude, and shortening of PR and PRc interval at a daily dose of 0.5 mg/kg . Severe changes were observed at a daily dose of 1.0 mg/kg of ADM including an increase of heart rate, elevation of R wave amplitude, reduction of S and T wave amplitude, and shortening of QT interval . The electron microscopic examination revealed that THP-treated hamsters showed separation of intercalated discs, formation of myelin structure, and dilatation of T-tubules at a daily dose of 1.0 mg/kg . Similar changes were caused by ADM at a daily dose of 0.25 to 1.0 mg/kg.(ABSTRACT TRUNCATED AT 400 WORDS) Jpn J Antibiot, 1986 Feb, 39(2), 507 - 25 {A study on the effect of (2"R)-4'-O-tetrahydropyranyladriamycin, a new antitumor antibiotic, on reproduction . III . Its effects on perinatal and postnatal rats}; Kurebe M et al.; This paper describes effects of (2"R)-4'-O-tetrahydropyranyladriamycin hydrochloride (THP) on perinatal and postnatal rats . The drug was administered intravenously to female rats at 0.01, 0.03 or 0.1 mg/kg daily from day 17 of pregnancy to 21 days after delivery . Results were described below . At any dose levels tested, THP did not affect the body weight gain, food and water consumption by pregnant rats, and length of gestation period or delivery rate . However, at the highest dose level, THP decreased spleen weight . THP, at any dose levels, did not have toxic effect on development, physiological functions, behavior, mating, fertility or pregnancy of the first generation offspring (F1) . At the highest dose of 0.1 mg/kg, however, THP produced delayed ossification of sacrococcygeal vertebra in the second generation fetuses (F2) . The results suggest that the maximum "no effect" dose of THP to pregnant rats and offsprings is 0.03 mg/kg/day intravenously. Jpn J Antibiot, 1986 Feb, 39(2), 477 - 506 {A study of the effect of (2"R)-4'-O-tetrahydropyranyladriamycin, a new antitumor antibiotic, on reproduction . II . Its teratogenicity in rats and rabbits}; Kurebe M et al.; This paper describes the embryotoxicity and teratogenic effects of (2"R)-4'-O-Tetrahydropyranyladriamycin (THP) . The drug was administered intravenously to female rats at 0.01, 0.03, 0.1 or 0.3 mg/kg daily from day 7 to day 17 of pregnancy and to female rabbits at 0.01, 0.05 or 0.1 mg/kg daily from day 6 to day 18 of pregnancy . Results were summarized as follows . Rats THP, at the highest dose of 0.3 mg/kg, decreased body weight gains of pregnant females . This dose caused a decrease in body weights of fetuses, tendencies to increase the rate of death of fetuses or of resorption, an increase in the number of lumbar vertebrae and a delayed ossification of forelimbs of fetuses . Other parameters were not affected by THP at any dose levels . At any dose levels, THP did not produce external, visceral or skeletal malformations in the offspring (F1), nor did it affect the development, physiological functions, behavior, mating, fertility or pregnancy of the offspring . However, at the highest dose level, THP decreased the weight of testes of the offspring . The results suggest that the maximum "no effect" dose level of THP to pregnant females and offspring is 0.1 mg/kg/day intravenously . Rabbits The highest dose of THP, 0.1 mg/kg, decreased the consumption of food and water by pregnant females, but at any dose levels, it did not affect their body weight gain . THP did not cause teratological effects such as external malformation or visceral and skeletal anomalies in the fetuses at any dose levels tested . The results suggest that the maximum "no effect" dose of THP is 0.05 mg/kg/day intravenously to pregnant females and above 0.1 mg/kg/day intravenously to fetuses. Jpn J Antibiot, 1986 Feb, 39(2), 463 - 76 {A study on the effect of (2"R)-4'-O-tetrahydropyranyladriamycin, a new antitumor antibiotic, on reproduction . I . Its effect on the fertility of rats}; Kurebe M et al.; The effect of a new antitumor antibiotic on the fertility was studied using SD rats . (2"R)-4'-O-Tetrahydropyranyladriamycin (THP) was administered to each rat at 0.01, 0.03 or 0.1 mg/kg daily . Males were given the drug intravenously for 63 days prior to mating and during the mating period; females were given the drug intravenously from 14 days prior to mating until day 7 of pregnancy . All the pregnant rats were sacrificed on day 20 of pregnancy, followed by external, visceral and skeletal observations of their fetuses . Results were summarized as follows . THP, at 0.1 mg/kg, suppressed body weight gain in females during the late period of pregnancy but did not affect body weight gain in males . THP, at 0.1 mg/kg, increased the numbers of dead fetuses and of resorptions . It caused no external, visceral or skeletal anomalies at any dose levels . The results suggest that, in rats, the maximum "no effect" dose of THP is 0.03 mg/kg/day intravenously regarding fertility and fetal development. Jpn J Antibiot, 1986 Feb, 39(2), 403 - 28 Toxicological studies on (2"R)-4'-tetrahydropyranyladriamycin, a new antitumor antibiotic . Chronic toxicity study in rats; Tone H et al.; (2"R)-4'-O-Tetrahydropyranyladriamycin X HCl (THP), a new anthracycline antitumor antibiotic, was administered to Sprague-Dawley rats (each group 20 rats) intraperitoneally at dosages of 0.001, 0.008, 0.06 and 0.3 mg/kg/day for 53 weeks . Piloerection, loose feces or perianal staining and thin or emaciated build were observed from week 12 in rats receiving 0.06 or 0.3 mg/kg/day . All rats receiving 0.3 mg/kg/day and 3 males and 1 female receiving 0.06 mg/kg/day died or were prematurely sacrificed in the period from weeks 13 to 44 . The overall food consumption and body weight gain of both sexes receiving 0.06 or 0.3 mg/kg/day were lower than those of the controls . Hematological examination showed low leucocyte counts, disturbance in neutrophil and lymphocyte number and low erythrocytic characteristics in animals receiving 0.06 or 0.3 mg/kg/day . At necropsy, macroscopic changes were found at the injection site, throughout the gastrointestinal tract and in the male reproductive system in rats receiving 0.06 or 0.3 mg/kg/day . Microscopic examination revealed decrease in the small lymphocyte population in the hematopoietic and lymphoid system in rats receiving 0.008 to 0.3 mg/kg/day . Degeneration of the germinal epithelium of the subcapsular tubules of the testes, gastric ulceration, epithelial adnexal atrophy of the skin and chronic cellulitis and necrosis at the injection sites were also observed . No rats receiving 0.001 mg/kg/day were affected in these respects. Jpn J Antibiot, 1986 Feb, 39(2), 327 - 50 Toxicological studies on (2"R)-4'-O-tetrahydropyranyladriamycin, a new antitumor antibiotic . Subacute toxicity study in rats; Tone H et al.; (2"R)-4'-O-Tetrahydropyranyladriamycin X HCl (THP), a new anthracycline antitumor antibiotic, was administered to Sprague-Dawley rats intraperitoneally for 13 weeks . In rats receiving 0.4 mg/kg/day, piloerection, emaciation, loose feces and thickening of the injection site were evident, and 7 males and 2 females died after week 12 . Inferior body weight gain was observed in both sexes starting week 4 approximately 6 . The food consumption also decreased . Hematological examination revealed lower counts of total leucocyte and lymphocyte . At termination there were lower spleen, thymus and testes weights, thickening of the walls of the intestine and stomach, gastric ulceration, presence of ascitic fluid, and congestion and thickening at the injection site . Decreases in the lymphocyte populations of the thymus, spleen and lymph nodes were observed microscopically . A decrease in the number of hematopoietic cells in the bone marrow and a degeneration of the germinal epithelium in the testes were also seen, as were gastrointestinal disturbances . These treatment-related effects were mainly confined to rats receiving 0.4 mg/kg/day and to a lesser extent, to rats receiving 0.1 mg/kg/day . The effects on rats receiving 0.025 mg/kg/day were only at the microscopic level . No rats receiving 0.006 mg/kg/day were toxicologically affected. J Pharmacobiodyn, 1986 Feb, 9(2), 211 - 7 Enhanced small intestinal absorption of beta-lactam antibiotics in rats in the presence of monodesmosides isolated from pericarps of Sapindus mukurossi (Enmei-hi); Yata N et al.; Monodesmoside, saponin A, B and C, isolated from pericarps of Sapindus mukurossi (Enmei-hi) have been shown to promote absorption of poorly absorbed beta-lactam antibiotics by the small intestine using an in situ loop method . Monodesmosides were solubilized with ginseng crude saponin extract, a mixture of bisdesmosides, saponin X, Y1 and Y2 which were isolated also from Sapindus mukurossi . These solubilizing agents were demonstrated not to influence the absorption promoting effect of monodesmosides . Among the monodesmosides, saponin B showed the greatest effect . No influence of osmolarity of the administered solution on the absorption promoting action was observed . The promoting functions of the three monodesmosides for the small intestinal absorption of antibiotics were suppressed by Ca2+ ion coexisting in the administered solution. Vestn Khir Im I I Grek, 1986 Feb, 136(2), 8 - 13 {Use of interstitial antibiotic electrophoresis with chronic pneumonia patients}; Uglov FG et al.; Interstitial electrophoresis of antibiotics included in the complex of curative measures was shown to be highly effective for the treatment of chronic pneumonia . The conclusion was made on the basis of an analysis of results of treatment of 128 patients with chronic pneumonia. J Dairy Sci, 1986 Feb, 69(2), 535 - 41 Postthaw survival and fertility of frozen bull spermatozoa treated with antibiotics and detergent; Ahmad K et al.; Five factorial experiments were conducted, each with 10 bulls, three extenders, and six antibiotic treatments to determine safe levels of new antibiotics to add to bull spermatozoa . Dicloxacillin, cephapirin, ceforanide, gentamicin, and minocin were added at five concentrations to whole milk, egg yolk-Tris, and egg yolk-Tris detergent (sodium triethanolamine lauryl sulfate) extenders with penicillin and streptomycin as a control . Semen was extended to 20 X 10(6) sperm/ml, packaged in .5-ml straws, frozen and stored in liquid nitrogen, and thawed at 35 degrees C for 30 s . Two people assessed postthaw percentage of motile spermatozoa from two straws per treatment . Bulls and extenders always affected sperm motility significantly . Percentage of intact acrosomes of spermatozoa was assessed in selected treatments but did not differ in any experiment . Sodium triethanolamine lauryl sulfate tended to improve cryopreservation of spermatozoa . Percentage of motile spermatozoa in milk declined when concentrations of dicloxacillin exceeded 200 micrograms/ml or when gentamicin, as Gentocin, exceeded 500 micrograms/ml . Minocin was toxic at all levels tested in egg yolk and was nontoxic to sperm in milk extender at concentrations less than or equal to 100 micrograms/ml . Cephapirin and ceforanide were innocuous at all concentrations tested (200 to 2000 micrograms/ml) . Fertility with cephapirin (500 micrograms/ml) added to an extender containing control antibiotics resulted in a 56-d nonreturn rate of 75.5 versus 72.1% for the control. Fundam Appl Toxicol, 1986 Feb, 6(2), 335 - 8 Pain on injection and muscle irritation: a comparison of animal models for assessing parenteral antibiotics; Comereski CR et al.; Pain on injection due to parenteral administration of cephaloridine, cephalothin, and cefoxitin with or without 1% lidocaine was examined in a rat paw-lick model and the results compared with those obtained in a rabbit intramuscular model of irritation . In both animal models, cephaloridine caused similar or a slightly greater response than sterile water . Conversely, cefoxitin and cephalothin caused a much greater reaction than water in both models . The only major difference in the rankings by the two models was with formulations in which an anesthetic agent was incorporated into the diluent . As expected, the presence of a local anesthetic masked pain on injection but not muscle damage . The rat paw-lick model is an alternative to the traditional rabbit muscle irritation model for rapidly assessing both pain on injection and muscle irritation of parenteral formulations. J Otolaryngol, 1986 Feb, 15(1), 15 - 20 Age related cochlear toxicity from noise and antibiotics--a review; Bhattacharyya TK et al.; Laboratory experimental evidence indicates that there is an age related susceptibility to cochlear damage from noise exposure and ototoxic antibiotics . In some rodents there is a critical period of auditory development during which there is greater vulnerability to such damage and, in some species, noise induced damage is influenced by genotype . Available data from patients are inconclusive in this regard . Further careful studies are indicated in this area . All available evidence emphasizes that caution should be exercised in the use of ototoxic drugs during pregnancy, in neonates, young children, and older people. Genetika, 1986 Feb, 22(2), 339 - 42 {Induction of mutations in Streptomyces antibioticus}; Semykina LV et al.; Mutagenic action of UV-light, nitrosoguanidine and nitrosomethylbiuret was studied in Streptomyces antibioticus VNIIA 1607 . Nitrosomethylbiuret appeared to be most effective inducer of auxotrophic mutations (mutation frequency reached 15%) . By means of hybridological analysis, it was shown that heterokaryons predominated in the progeny of mixed cultures of multiply marked strains . The test for functional allelism using heterokaryons permitted us to divide 93 independently obtained mutations into 28 complementation groups. Arch Surg, 1986 Feb, 121(2), 191 - 5 Oxygen as an antibiotic . A comparison of the effects of inspired oxygen concentration and antibiotic administration on in vivo bacterial clearance; Knighton DR et al.; Since prophylactic antibiotics and changes in tissue partial pressure of oxygen may affect bacterial clearance by different mechanisms, we tested the effects of hypoxia, hyperoxia, and normoxia with and without antibiotic administration on bacterial clearance . We found that improving tissue oxygenation by administration of normobaric oxygen decreased infectious necrosis as effectively as prophylactic antibiotic administration and that improved tissue oxygenation and antibiotic administration had an additive effect . We believe that a fraction of inspired oxygen of 45% should be added to prophylactic antibiotics as standard perioperative and postoperative care. Antibiot Med Biotekhnol, 1986 Feb, 31(2), 98 - 104 {Status and prospects in the use of biocatalysis in the synthesis of beta-lactam antibiotics}; Bartoshevich IuE et al.; The present world status of using biocatalysts for production of beta-lactam antibiotics and their semiproducts is analyzed and the biocatalytic and chemical methods for production of antibiotics are compared . The requirements to the quality of biocatalysts used in production of drugs are formulated and the criteria of the efficiency of biocatalytic production processes are presented . Interrelation between the requirements to the biocatalyst quality and the efficiency of the biocatalytic production processes is examined . The general principles of development of efficient enzymatic processes including biocatalytic processes in production of beta-lactam antibiotics as closed-loop and practically wasteless systems are discussed . The main advantages of the developed production processes are illustrated by an example of large-scale processes use in manufacturing of the basic products for synthesis of beta-lactam compounds. Chemioterapia, 1986 Feb, 5(1), 7 - 13 Sensitivity of 115 strains of the genus Brucella to some antibiotics (cephalosporins, ureidopenicillins and aminoglycosides); Gargani G et al.; The Authors tested piperacillin, azlocillin, aztreonam, cefotaxime, ceftizoxime, ceftriaxone, cefotetan, moxalactam, gentamicin, sisomicin and dibekacin, on about 120 strains of the genus Brucella, using as control drugs tetracycline, streptomycin and rifampicin . Cefotaxime, ceftizoxime, gentamicin, and sisomicin exhibited antibrucella activity comparable to that of tetracycline and just a little superior to that of rifampicin . Among the aminoglycosides tested, gentamicin, sisomicin and dibekacin were, in decreasing order, more active than streptomycin . For all the other drugs tested there was a large variability among the brucella strains, with roughly a peak of activity on the strains which have a history of repeated in vitro passages. J Antibiot (Tokyo), 1986 Feb, 39(2), 251 - 8 Aminoglycoside antibiotics . 7 . Dihydrostreptomycin analogues; Delaware DL et al.; Dihydrostreptomycin analogues with structural variations in their guanidino groups were prepared . The analogue with a methyl group on the guanidine at C-1 was nearly as active as dihydrostreptomycin against bacteria . However, the 2-imidazolin-2-ylamino substituent at C-1 eliminated activity . No analogue with a substituent on the C-3 guanidino group was active. FEBS Lett, 1986 Jan 20, 195(1-2), 203 - 8 Origin of sequence-specific recognition of DNA by non-intercalating anti-tumor antibiotics; Mrigank et al.; Partitioning of energy in the interaction of non-intercalating antibiotics (netropsin, netropsin without its cationic ends and two analogs of distamycin A) with different base sequences of B-DNA is studied here by the atom-atom potential technique and geometry optimization procedures . The results show that electrostatic forces contribute substantially to the stabilization energy as well as to the sequence specificity . The hydrogen-bonding term is also sequence specific and is significant in properly orienting the drug molecule . Relative roles of the hydrogen bonding and electrostatic interactions depend on the dielectric property of the medium. Biochim Biophys Acta, 1986 Jan 16, 854(1), 84 - 92 Synergistic incorporation of daunorubicin in erythrocytes in the presence of polyene antibiotics . Role of the membrane potential; Henry N et al.; The synergistic incorporation into red blood cells of the antitumor compound daunorubicin, in the presence of the polyene antibiotics amphotericin B and vacidin A, depended on the composition of the external medium . Synergism was observed only for concentrations of polyene antibiotics that induce cation permeability . The same synergistic effect was observed with the K+ selective carrier, valinomycin, but this had a different dependence on the external medium composition . By using the membrane probe 3,3'-dipropylthiadicarbocyanine (diS-C3-(5}, the synergistic effect was shown to occur under conditions where addition of the ionophores leads to hyperpolarization of the membrane. Vet Rec, 1986 Jan 11, 118(2), 34 - 5 Intramammary antibiotic preparations and their withholding times; Booth JM; The test for antibiotic residues in milk carried out by the Milk Marketing Board (MMB) of England and Wales was increased in sensitivity from 0.02 iu/ml penicillin or equivalent to 0.01 iu/ml on January 1, 1986 . The Veterinary Products Committee (VPC) has just completed a review of those intra-mammary antibiotic preparations which had licences of right . When assessing data for product licences the VPC decided that the concentration of antibiotic residues in milk should not exceed the concentrations listed in the 1969 Report of the Joint FAO/WHO Expert Committee on Food Additives . In this publication the level of 0.006 ppm for penicillin corresponds to 0.01 iu/ml which is the level that the MMB will also be using. Geburtshilfe Frauenheilkd, 1986 Jan, 46(1), 37 - 42 {Neonatal septicemia and bacterial neonatal infection . Manifestation and course in early antibiotic therapy}; Karitzky D et al.; The authors studied in the Paediatric Department of the Leverkusen Municipal Hospital retrospectively the influence of an early dose of antibiotics (broad-spectrum penicillin combined with an aminoglycoside) in respect of the manifestation of bacterial newborn infections in infants with an increased risk of infection, during a period of 3 years (1981-1983) . Among the infants born in the Gynaecological Department of the Leverkusen Municipal Hospital (exact data were available on the number of births and referrals) the incidence of bacterial newborn infections was 3.3% referred to the total number of deliveries (n = 3598); 0.7% of these newborn has sepsis . In the total group of children treated for newborn infection, the infection mortality was 5.5%; the mortality of the manifest newborn sepsis was 16.2%, i.e . lower than reported in literature . Early administration of antibiotics proved particularly effective in preventing purulent bacterial meningitis of newborn; this disease did not occur with any of the infants observed during the study period . Diagnosis of newborn infection included discolouration of the skin, respiratory disturbances, fever, shift to the left in the differential blood picture, and anaemia; these signs proved particularly suitable for arriving at a correct diagnosis . Identification of the pathogens was most frequently successful in gastric juice culture and anal smear . The latency period of more than 24 hours between rupture of the amnion and delivery does not represent an increased risk of infection for the newborn, as our results confirm, and this is, therefore, not an indication for initiating prophylaxis with antibiotics if there are no other abnormal findings. Ann Ophthalmol, 1986 Jan, 18(1), 22 - 4 A comparison of therapeutic bandage lenses, tarsorrhaphy, and antibiotic and hypertonic saline on corneal epithelial wound healing; Ali Z et al.; Bandage lenses, a complete tarsorrhaphy, chloramphenicol 0.5%, and sodium chloride 2% were tested for their effect on corneal epithelial wound healing in rabbits . The healing rate was decreased with bandage lenses and increased by tarsorrhaphy . There was no significant effect on healing rate with either chloramphenicol or hypertonic saline. J Antibiot (Tokyo), 1986 Jan, 39(1), 6 - 11 A new antitumor antibiotic, chromoxymycin . I . Taxonomic studies on the producing strain: a new subspecies of the genus Streptomyces; Iwami M et al.; A new subspecies of the genus Streptomyces, for which the name S . libani subsp . rubropurpureus subsp . nov . is proposed, is described . Soil isolate, strain No . 6362, produces a new antitumor substance chromoxymycin . The strain has a gray or red spore mass color, spiral spore chains with smooth spores, is nonchromogenic, and utilizes most carbon sources . Strain No . 6362 is most closely related to S . libani, although there are differences in colorization of reverse colony and spore chain morphology between each other . Those differences are not enough to establish a new species . It is suitable to consider that strain No . 6362 is identified as a new subspecies in the species of S . libani. J Antibiot (Tokyo), 1986 Jan, 39(1), 58 - 67 Glycopeptide antibiotics: a mechanism-based screen employing a bacterial cell wall receptor mimetic; Rake JB et al.; The evolution of a highly targeted screening program for the discovery of antibiotics of the glycopeptide (vancomycin) class is described . A holistic approach was utilized which optimized not just screening techniques but also the selection of candidate producer cultures and their growth under conditions which enhanced production of target compounds . Two screen techniques were utilized; differential inhibition of a vancomycin-resistant strain and its susceptible parent, and a specific antagonism screen using the reversal of glycopeptide activity by a tripeptide analog of the glycopeptide receptor, diacetyl-L-lysyl-D-alanyl-D-alanine . The latter screen was 2- to 32-fold more sensitive to known glycopeptides than the former, and was absolutely specific, yielding no false positive responses . The use of the tripeptide antagonism assay, combined with optimized culture selection and growth conditions yielded novel glycopeptide antibiotics at a rate of 1 per 320 cultures screened . With a holistic approach to screening and properly optimized techniques, large numbers of cultures do not need to be examined in order to discover novel antibiotics. Antibiot Med Biotekhnol, 1986 Jan, 31(1), 49 - 52 {Endolymphatic antibiotic therapy in acute inflammatory diseases in urological practice}; Slutskin IM et al.; Enteral, intramuscular or intravenous antibiotic therapy is the basic current method of treating acute inflammatory diseases of the scrotum . However, the efficacy of the treatment is not always sufficient . A new endolymphatic method of antibiotic administration is discussed . Its high efficacy is shown . The method provides a more rapid clinical recovery and decreases the number of complications . A history of a patient given a treatment course with endolymphatic administration of the antibiotic is presented . Endolymphatic administration of antibiotics is recommended as the main method of antibiotic therapy in treatment of patients with acute inflammatory diseases of the scrotum. Arch Surg, 1986 Jan, 121(1), 73 - 6 Effect of antibiotics and sedatives on normal neutrophil nicotinamide-adenine dinucleotide phosphate-reduced oxidase activity; Moon BC et al.; The effects of antibiotics and other commonly used medications on the human polymorphonuclear neutrophil leukocytes' (PMNs) nicotinamide-adenine dinucleotide phosphate-reduced (NADPH) oxidase activity have been investigated in vitro . Five antibiotics (penicillin G sodium, cefamandole nafate, metronidazole hydrochloride, clindamycin phosphate, and tobramycin sulfate, and a triple combination of penicillin G sodium-metronidazole hydrochloride-tobramycin sulfate) and two sedatives (morphine sulfate and diazepam) were incubated with normal human PMNs at therapeutic, infratherapeutic, and supratherapeutic drug levels . The superoxide dismutase-inhibitable, NADPH-dependent reduction of cytochrome C in the PMNs was studied after stimulation with formyl-methionyl-leucine-phenylalanine . Tobramycin sulfate and the triple combination of penicillin G sodium-metronidazole hydrochloride-tobramycin sulfate significantly reduced the NADPH oxidase activity at all dosages studied . Clindamycin phosphate, morphine sulfate, and diazepam also showed significant reduction at therapeutic and supratherapeutic concentrations . Penicillin G sodium, cefamandole nafate, and metronidazole hydrochloride did not cause a decrease in enzyme activity at any levels tested . We conclude that NADPH oxidase activity can be adversely affected by the circulating levels of common antibiotics and sedatives. Vet Med Nauki, 1986, 23(8), 70 - 7 {Effect of feed antibiotics on ampicillin pharmacokinetics in chickens}; Mutafchieva R et al.; Experimental studies with broiler birds revealed that medicated feed (flavophospholipol, vitamyacin A, and the A-149 antibiotic in stimulative doses), offered in the course of two weeks, led to changes in the pharmacokinetic parameters of ampicillin administered i/v (in the form of ampicillin-Na) and via the crop (in the form of ampicillin-trihydrate at 30 mg/kg) . It was found that the biologic half-life of ampicillin-Na was prolonged by A-149, and was shortened by vitamicin A, and to a certain extent--by flavophospholipol; the seeming volume of distribution was shown to rise by A-149, and to a certain extent--by flavophospholipol, and was lowered by vitamycin A . The biologic half-life of ampicillin-trihydrate was prolonged by all three ergotropic agents . The systematic bioavailability of ampicillin-trihydrate rose with the use of A-149, and dropped with the use of vitamycin A, and to a lower extent--with the use of flavophospholipol . On the base of the changes established in the pharmacokinetic parameters ampicillin-trihydrate was dosed for use via the drinking water as follows: 196 mg/l simultaneously with flavophospholipol in the feed, 156 mg/l--with the use of vitamycin A, 148 mg/l--when used with the A-149 antibiotic, and 216 mg/l--when administered at no medication via the feed. J Orthop Res, 1986, 4(4), 494 - 8 Antibiotic stability in an implantable pump; Perry CR et al.; We measured the stability of vancomycin, amikacin, netilmicin, tobramycin, gentamicin, clindamycin, and aztreonam in an implantable drug pump . Two pumps were filled with the antibiotic being tested and were incubated at 37 degrees for 3 weeks . Samples were taken daily . At 3 weeks the pumps were disassembled and examined microscopically for signs of deterioration . If the pumps were intact, bioassays were used to quantitate the biologic activity of each daily antibiotic sample . Vancomycin degraded the pump . Amikacin, netilmicin, tobramycin, gentamicin, clindamycin, and aztreonam had no effect on the pump and maintained their biologic activity over the 3-week period. Int J Clin Pharmacol Res, 1986, 6(5), 369 - 72 Possibility of interaction among antibiotics and mucolytics in children; Principi N et al.; A controlled clinical trial in children with acute infections of the lower respiratory tract was carried out to see whether or not treatment with ambroxol could bring about faster and better results . One hundred twenty children with acute lower respiratory tract infections were all given antibiotics plus, at random, either ambroxol (1.5-2.0 mg/kg body weight orally) or a placebo . The duration of the trial was ten days . All the patients in both groups were cured clinically . However, remission of the cough, of the chest pathological signs, as well as the improvement of the lung radiographical pictures were significantly more rapid in children treated with ambroxol than in those who received the antibiotic alone . Ambroxol was tolerated perfectly by all the children. Z Erkr Atmungsorgane, 1986, 167(1-2), 47 - 51 {Resistance behavior of atypical mycobacteria to antibiotics and sulfonamides}; Neubert R; In the work presented here a simple method is described for sensitivity testing of atypical mycobacteria against antibiotics and sulphamerazin . The sensibility is tested with susceptibility discs in the liquid medium (culture medium 66 without agar) against Amikacin, Ciprofloxacin, Erythromycin, Gentamycin, Lincomycin, Sisomicin and Sulphamerazin . Following strains of atypical mycobacteria were examined: M . kansasii, M . xenopi, M . avium-complex, M . fortuitum . The aminoglycosides, Ciprofloxacin and Erythromycin show a wide spectrum of effects . We state a good sensibility of M . kansasii and M . fortuitum towards lincomycin and of M . kansasii and M . xenopi towards Sulphamerazin . The heterogeneity in sensibility of the single strains of some species already described is confirmed . This fact makes it necessary to carry out a sensitivity test of each strain of atypical mycobacteria before therapy. Chemotherapy, 1986, 32(5), 464 - 7 Effects of various antibiotics on antibody-producing cells of mouse spleen; Ogawa M et al.; The inhibitory effect of various beta-lactams on antibody production in the spleen was evaluated in mice immunized with sheep red blood cells by Cunningham's method . With a few exceptions, cephem derivatives were more effective than the penicillins tested in inhibiting the production of antibodies in the spleen of mice . This tendency was especially marked with cefsulodin, cefmenoxime, cefotiam and ceftazidime . However, no effect was obtained with 6-aminopenicillanic acid or 7-aminocephalosporanic acid . Our findings suggest that the difference among various beta-lactams in inhibitory effect on antibody production resulted from the difference in activities of beta-lactams with different side chains at the 6- or 7-positions. Invest New Drugs, 1986, 4(1), 3 - 10 Biological and biochemical activities of the novel antitumor antibiotic PD 114,759 and related derivatives; Fry DW et al.; A complex of novel and exceptionally potent antibiotics has been evaluated for antitumor activity in vitro and in vivo and characterized with regard to their ability to cause DNA strand scission . The major component, PD 114,759, was quite active against all in vitro tumor systems including the human tumors, MCF-7 breast, HCT-8 colon, and A549 lung and the murine tumors M16/c mammary, Lewis lung, Pan 02 pancreas and L1210 leukemia . ID50 values ranged from 2-57 pg/ml . In vivo this agent produced significant increases of host life spans in mice bearing L1210 leukemia, B16 melanoma and the M5076 sarcoma . Further, it inhibited growth of subcutaneous implants of the Ridgway osteogenic sarcoma by 80% and growth of the MX-1 human mammary xenograft by 90-95% . PD 114,759, however, had no activity against the colon adenocarcinoma 11a or mammary adenocarcinoma 16c . Chinese hamster ovary cells exposed for 24 hours to concentrations of PD 114,759 ranging from 18 to 37 pg/ml accumulated in the S and G2+M phases of the cell cycle with a corresponding decrease in G1 . Higher concentrations of drug apparently stopped any progression through the cell cycle . PD 114,759 caused significant DNA single strand breaks in L1210 cells exposed for 1 hour to drug concentrations as low as 20 pg/ml and the frequency of these lesions increased in proportion to the drug concentration . A portion of these DNA breaks appeared to be associated with protein . In contrast, no double strand DNA breaks were detected at the highest drug concentration tested (100 pg/ml). Nauchnye Doki Vyss Shkoly Biol Nauki, 1986, (2), 87 - 9 {Effect of orthophosphate on the formation of the antibiotic nonactin}; Nefelova MV et al.; The potassium orthophosphate added to the media with developing actinomycetes inhibits the nonactin macrotetrolide antibiotic but causes the increase of mycelium growth . The degree of inhibition depends on the quantity of orthophosphate and almost doesn't depend on the time of its adding to the actinomycetes culture . The degree of phosphorus consumption by actinomycetes is higher, the more its content in the media . The antibiotic synthesis takes place during the phosphorus consumption but not after its exhaustion from the media. Cancer Res, 1986 Jan, 46(1), 381 - 5 Rhizoxin, a macrocyclic lactone antibiotic, as a new antitumor agent against human and murine tumor cells and their vincristine-resistant sublines; Tsuruo T et al.; Rhizoxin, isolated from a plant pathogenic fungus which causes rice seedling blight, inhibits the mitosis of the tumor cells in a manner similar to that of Vinca alkaloids as revealed by morphological study and flow cytometry analysis . This new 16-membered macrocyclic lactone showed similar chemotherapeutic effects to those of vincristine against L1210 and P388 leukemia-bearing mice . The drug is also effective against B16 melanoma inoculated i.p . or s.c . Rhizoxin, in contrast to the ansamacrolide, maytansine, was effective against human and murine tumor cells resistant to vincristine and Adriamycin in vitro and in vivo . A maximum 60% increase in life span was obtained in mice inoculated with P388 leukemia resistant to vincristine . Rhizoxin showed greater cytotoxicity in cultured tumor cells than did vincristine . Rhizoxin seems to bear consideration for further development as a new chemotherapeutic agent. J Basic Microbiol, 1986, 26(3), 169 - 72 Butylmaduramycin, a new antibiotic from Actinomadura rubra; Strauss DG et al.; Butylmaduramycin, a new derivative of maduramycin was isolated from the culture medium of a mutant strain of Actinomadura rubra . This communication describes some biological and physico-chemical characteristics of the new antibiotic. Cancer Chemother Pharmacol, 1986, 17(3), 218 - 22 Influence of the antibiotics piperacillin, doxycycline, and tobramycin on the pharmacokinetics of methotrexate in rabbits; Iven H et al.; In rabbits methotrexate (MTX) plasma concentrations showed a triexponential decline after short-term infusion (12 mg/kg in 10 min) . Probenecid (50 mg/kg PO 1 h before MTX) and piperacillin (100 mg/kg SC 10 min before MTX plus 50 mg/kg SC 4 h later) increased the plasma concentrations of MTX and its metabolite 7-hydroxy-methotrexate (7-OH-MTX) 40 min to 6 h after the end of MTX infusion . The total body clearance of MTX was reduced, while the elimination half-life and the drug distribution to the peripheral body compartments were unchanged . Doxycycline (5 mg/kg PO 30 min before MTX) had no influence on the pharmacokinetics of MTX . Tobramycin was ineffective when given either only on the day of MTX infusion (2 mg/kg SC, 5 min before MTX and 2 mg/kg SC 4 h later) or as a 5-day pretreatment (2 X 2 mg/kg SC daily) . The influence of probenecid and piperacillin can be explained by a reduction of the renal elimination of MTX via the tubular transport mechanism for organic acids . This interaction occurred with therapeutic drug concentrations and thus may be clinically relevant. Padiatr Padol, 1986, 21(2), 183 - 7 Antibiotic-associated pseudomembranous colitis as cause of intestinal obstruction in a five-day-old newborn; Miholic J et al.; The case report is presented of a newborn that developed pseudomembranous colitis and intestinal obstruction after antibiotic therapy with cefoxitin and gentamicin in the first week of life . At laparotomy on the fifth day a complete obliteration of the descending colon by pseudomembranes was encountered . After resection of the diseased segment the recovery was uneventful . We believe this case is the first to be published of antibiotic-associated pseudomembranous colitis causing intestinal obstruction. Am J Nephrol, 1986, 6(2), 149 - 51 Antibiotic-associated interstitial nephritis and nephrotic syndrome; Baum M et al.; The combination of interstitial nephritis and minimal-change nephrotic syndrome has been well described in adults receiving nonsteroidal anti-inflammatory agents . The association of interstitial nephritis and minimal-change nephrotic syndrome has recently been described in 1 adult patient receiving ampicillin and in 1 patient receiving rifampin . We describe an 8-month-old child who developed reversible interstitial nephritis and minimal-change nephrotic syndrome while taking antibiotics. Jpn J Antibiot, 1986 Jan, 39(1), 259 - 63 {Toxicological studies on (2''R)-4'-O-tetrahydropyranyladriamycin, a new antitumor antibiotic . Its acute toxicity in rats}; Kurebe M et al.; (2''R)-4'-O-Tetrahydropyranyladriamycin (THP), a new antitumor antibiotic of anthracycline derivative, was given to Jcl-SD strain rats through intravenous (i.v.), intraperitoneal (i.p.), subcutaneous (s.c.) or oral (p.o.) administration routes and the animals were observed in respect of mortality, clinical signs and body weight for 21 days . Autopsy was done and histopathology on the tissues showing macroscopic abnormality was performed . The results were summarized as follows . Values of LD50 were 18.09 mg/kg i.v., 22.58 mg/kg i.p., 25.39 mg/kg s.c . and above 1,013 mg/kg p.o . for males and 18.07 mg/kg i.v., 20.30 mg/kg i.p., 21.76 mg/kg s.c . and above 1,013 mg/kg p.o . for females . No significant difference was found in LD50 values of different sexes . When higher than lethal dose levels of THP was given to animals, their clinical signs grew worse and weight loss occurred in about 5 days after the administration of the drug . Thereafter, deaths were observed . Macroscopic and microscopic observations on dead and survived rats revealed atrophy of spleen and thymus, whity clouding of spleen capsule, hemorrhage in mucosa of glandular stomach and congestion and hemorrhage in testes . These results suggest that THP shows weaker acute toxicity to rats than doxorubicin does, but the toxic effect of THP is approximately the same as that of other anthracycline derivatives. Jpn J Antibiot, 1986 Jan, 39(1), 250 - 8 {Toxicological studies on (2''R)-4'-O-tetrahydropyranyladriamycin, a new antitumor antibiotic . Acute toxicity study in mice}; Tone H et al.; A new antitumor anthracycline antibiotic; (2''R)-4'-O-tetrahydropyranyladriamycin hydrochloride (THP) was administered to ddY mice via different routes for acute toxicity studies . The LD50 values were calculated from mortality rates during a 14-day observation period, and were 14-21 mg/kg when i.v., i.p . or s.c . route was used and 420-570 mg/kg when the drug was given p.o . Upon administration of the drug, mice showed depression of spontaneous activity, anorexia, diarrhea and slight alopecia . Autopsy of the mice killed by the drug revealed atrophy of thymus, spleen, testes, uterus and ovaries, and congestion and hemorrhage in the intestines . The mice which survived through the observation period, however, showed only atrophy of thymus and sexual organs. J Clin Microbiol, 1986 Jan, 23(1), 11 - 6 Determination of endotoxin in injectable antibiotic preparations by the chromogenic assay method using a Limulus reagent (Tachypleus hemocyte lysate) and a chromogenic substrate; Yano S et al.; The effects of 50 antibiotics on the detection and determination of bacterial endotoxins by the chromogenic method using a Limulus reagent (Tachypleus hemocyte lysate) and a chromogenic substrate of p-nitroaniline derivatives were tested, and the antibiotic concentration for 50% inhibition of the chromogenic reaction in the presence of 0.5 ng of endotoxin (Escherichia coli 0111:B4) per ml was estimated . All the antibiotic preparations were depyrogenized by ultrafiltration treatment before they were subjected to the test . The reaction was conducted in the presence of a high concentration (0.5 M) of Tris buffer to constantly maintain the pH of the reaction mixture, and liberated p-nitroaniline was determined by high-pressure liquid chromatography . Several aminoglycosides (amikacin, bekanamycin, kanamycin, and streptomycin sulfate), bleomycin hydrochloride, and fosfomycin disodium showed no inhibition of the reaction up to 20 mg/ml . However, other antibiotics, including penicillins, cephalosporins, macrolides, and tetracyclines, inhibited the reaction concentration dependently . Polymyxin B sulfate was the most potent inhibitor, with less than 8 micrograms/ml for 50% inhibition . It was concluded that the chromogenic method can be applied to the detection and determination of endotoxin in most of the antibiotic preparations . An application of this method to carbenicillin disodium preparations was exemplified. Soc Work Health Care, 1986 Fall, 12(1), 93 - 101 Social work in a home intravenous antibiotic therapy program; Sharp JW; Home intravenous antibiotic therapy (HIVAT) grew out of one hospital's experience with home parenteral nutrition . Because of current accelerated pace of discharge planning, the social worker plays a major role in choosing appropriate candidates for this program and in helping them solve practical and affective problems . Patients report a high degree of satisfaction with this homecare plan . Benefits such as early return to employment are noted . Shortened hospital stays lower treatment costs . The program is adaptable for many patients where medical treatment initiated in the hospital continues at home. Zentralbl Chir, 1986, 111(24), 1519 - 25 {Serum level of antibiotics in burn patients}; Syposs T et al.; Antibiotic serum levels were recorded from 100 patients with burns . Antibiotic doses to ensure effective serum levels were found to be in excess of maximum values quoted as necessary by manufacturers, provided that serum creatinine was normal . These findings were in agreement with literature data . This was the first instance to check on serum levels, following oral administration of antibiotics . Differences between individual patients may be considerable, probably due to variable renal blood supply and other factors . Individual dosage with control of serum levels is, therefore, recommended . Specific dosage recommendation for patients with burns would be desirable for hospital practice. Folia Microbiol (Praha), 1986, 31(5), 402 - 21 Enzymes of secondary metabolism and the biosynthesis of macrolide antibiotics; Neuzil J et al.; Enzymes participating in the biosynthesis of macrolide antibiotics are reviewed . Enzyme activities are known to play a pivotal role in the formation of biologically active compounds . Hence it is essential to understand these enzymes, their properties and regulation . Macrolide antibiotics represent a relatively compact group of natural products and include several excellent model compounds suitable for enzyme studies that could be generalized to other oligoketide antibiotics. Med Toxicol, 1986 Jan-Feb, 1(1), 32 - 46 Adverse reactions and interactions with newer cephalosporin and cephamycin antibiotics; Norrby SR; In this review, adverse reactions and interactions associated with the use of the newer cephalosporins and cephamycins are surveyed; special emphasis is placed on those reactions specific for some of these newer agents, namely disulfiram-like reactions with alcohol, effects on prothrombin synthesis, and lower gastrointestinal tract reactions . It is apparent that cephalosporins with a 3-methylthiotetrazole side-chain in the cephem nucleus cause clinically significant side effects more frequently than those without such a moiety . While still having a high degree of safety, cephalosporins with this chemical structure clearly have a higher degree of toxicity than those without this side-chain. Int J Immunopharmacol, 1986, 8(7), 723 - 9 Suppressive effects of B-lactam-antibiotics on in vitro generation of cytotoxic T-cells; Huegin AW et al.; The in vitro effect of several compounds containing the B-lactam structure (including 6-aminopenicillanic acid, piperacillin, 7-aminocephalosporanic acid, ceftazidime and clavulanic acid) on the generation of cytotoxic lymphocytes was investigated in two different in vitro systems: (1) generation of virus specific cytotoxic T-cells and (2) proliferation of lymphocytes were assessed in secondary in vitro anti-viral immune responses . Both activities were suppressed by B-lactams in a dose-dependent manner . In these experiments, as found previously with human in vitro granulopoesis and proliferation of the human erythroleukaemic cell line K-562, cephalosporins and clavulanic acid were five to twenty times more suppressive than penicillins . Since concentrations that were effective in vitro are being achieved, particularly with cephalosporins, in the serum of patients, the possible clinical consequences of our findings may have to be taken into consideration. Acta Obstet Gynecol Scand, 1986, 65(5), 459 - 61 Treatment of abscesses in the vulva . Conventional open treatment versus primary suture under antibiotic cover; Larsen T et al.; Seventy patients were treated for a subcutaneous abscess in the vulva . In 35 consecutive patients the abscess was treated conventionally with deroofing of the abscess and wet dressings . In the other 35 consecutive patients the abscess was treated by incision, curettage and primary suture under antibiotic cover with a single dose of clindamycin . In the conventionally treated group the median stay in hospital was 7 days and the median healing time 18 days . In the group treated by primary suture the median stay in hospital was 2 days and the median healing time 7 days (P less than 0.0001) . Recurrence of abscess was observed in one patient in each group . No other complications were observed in either group . It is concluded that vulvar abscesses may be treated safely and advantageously by primary suture under antibiotic cover. Scand J Infect Dis, 1986, 18(5), 381 - 8 The use of antibiotic serum levels to predict concentrations in tissues; Ryan DM et al.; A review of the literature shows that antibiotic concentrations in tissues and tissue fluids are often quoted as being different in profile to concurrent serum levels . To study the relationship between serum and tissue concentrations we analysed published studies where different experimental models were tested simultaneously . In some models serum levels predicted tissue levels while in others they did not . The factors likely to be responsible for the differences were examined . The most important of these factors was tissue geometry (surface area to volume ratio; SA/V) . Serum levels predicted tissue levels in models where the SA/V was high (greater than 60) but not where the SA/V's were low (less than 10); here the antibiotic concentrations were lower and more prolonged than serum levels . These observations can be extrapolated to the clinical situation . In most situations involving prophylaxis or treatment of infections in non-specialised tissues (naturally high SA/V), serum levels will closely reflect levels in extracellular tissue fluid where most bacterial infections are located. Drugs Exp Clin Res, 1986, 12(6-7), 613 - 8 Interaction of polyene antibiotics with membrane lipids: physicochemical studies of the molecular basis of selectivity; Bolard J; From various studies on the interaction of amphotericin B with unilamellar lipid vesicles, it appears that the strength of the binding does not depend only on the presence of sterol molecules in the membranes; and that several bound amphotericin B species are in competition, their relative amounts depending on the nature and percentage of sterol in the lipid bilayer . Bound amphotericin B molecules exchange rapidly between the membranes . It is therefore possible to add the antibiotic by transfer from amphotericin B-preloaded vesicles of dipalmitoylphosphatidylcholine, instead of direct addition . In these conditions the selectivity in the sensitivity to H+ leakage induced by amphotericin B between ergosterol- and cholesterol-containing vesicles is greatly enhanced . In the case of Mycoplasma laidlawii cells, a preliminary increase of K+ cellular content is observed when low doses of amphotericin B are added by transfer, an effect which is not observed with direct addition of the antibiotic. Drugs Exp Clin Res, 1986, 12(1-3), 275 - 82 Aclacinomycin A: clinical development of a novel anthracycline antibiotic in the haematological cancers; Warrell RP Jr; Aclacinomycin A (aclarubicin; ACM) is a new class II anthracycline antibiotic . Preclinical studies suggested that ACM had approximately equivalent antitumour activity but produced substantially less cardiotoxicity compared to other anthracyclines . Because of the recognized importance of these compounds in the treatment of haematological tumours, clinical trials of ACM were initiated in the late 1970s . ACM has been extensively evaluated in patients with relapsed leukaemia and advanced malignant lymphoma . Analysis of results compiled from Europe, Japan, and the United States shows that ACM is probably equivalent to doxorubicin for remission induction of patients with relapsed acute non-lymphoblastic leukaemia . Initial studies using ACM alone and in combination with standard cytotoxic drugs in previously untreated patients compare favourably with the best standard treatment for this disease . The antitumour activity of ACM in patients with acute lymphoblastic leukaemia or malignant lymphoma who have previously received doxorubicin or daunorubicin is low, and the issue of whether ACM lacks clinical cross-resistance to other anthracyclines is unresolved . Acute cardiac arrhythmias have been observed following administration of ACM, but congestive cardiomyopathy has been uncommon . Results to date all indicate that ACM has fulfilled its early expectations of antileukaemic activity and reduced toxicity . These hypotheses should now be evaluated in prospective, randomized trials with conventional anthracyclines. Vestn Khir Im I I Grek, 1986 Jan, 136(1), 64 - 6 {Operative treatment of osseous and osteoarticular paronychia by applying a closed suture to the wound and by prolonged intra-osseous administration of antibiotics}; Iusopov IuN et al.; Continuous intraosseous injections of antibiotics were used in 104 patients in the operative treatment of bony and osteo-articular panaritium with putting primary sutures on the wound . Healing by first intention was noted in most cases. Adv Exp Med Biol, 1986, 197, 155 - 62 Drug interactions with macrolide antibiotics: specificity of pseudo-suicide inhibition and induction of cytochrome P-450; Dansette PM et al.; Macrolide antibiotics like Erythromycin and Tri-acetyl oleandomycin (TAO) are metabolized to nitrosoderivatives which cause inactivation of Cytochrome P-450 by forming stable complex with the Iron of the hemoporphyrin . Several derivatives of erythromycin having lost their cladinose moiety are stronger inducer of liver cytochrome P-450 itself . The major form of cytochrome P-450 induced by all these macrolides in rat liver electrophoretically and immunologically indistinguishable from the major form induced by pregnenolone 16 alpha carbonitrile (PCN) . This form is particularly able to metabolize macrolide and to lead to the corresponding 456 nm absorbing cytochrome P-450 complexes in vivo and in vitro. Acta Otolaryngol Suppl, 1986, 429, 17 - 21 Antibiotics and sensorineural interactions . In vitro studies; Anniko M; Organ culture of the embryonic inner ear of the mouse results, under normal conditions, in a good morphological morphogenesis and cytodifferentiation of individual cells and tissues . Organ culture is performed during a period corresponding to the embryonic development in vivo . Continuing the culture period causes a deterioration of the organ culture explant . Only a minor portion of the total innervation of vestibular and cochlear parts of the labyrinth occurs prior to birth . Low dose exposure (1-10 micrograms/ml) of ototoxic antibiotics in the culture medium causes a primary morphologic damage of vestibular and cochlear hair cells and a markedly reduced number of nerve fibers and statoacoustic ganglion cells . Likewise the ingrowing nerve fibers are even more vulnerable to aminoglycoside antibiotics than the hair cells . Such a drug exposure in the in vitro system confirms (by a chemical deprivation of nerve fiber ingrowth to developing hair cells) that hair cell differentiation occurs at least initially independent of morphologic contact with ingrowing nerve fibers as was earlier shown using a mechanical excision of the statoacoustic ganglion. J Antibiot (Tokyo), 1986 Jan, 39(1), 141 - 8 Antibiotic binding to human polymorphonuclear neutrophils, mouse leukemia L1210 cells and mouse thymocytes; Gray GD et al.; This report describes a system in which antibiotics could be compared for binding to different mammalian cells . These included functional phagocytes (human polymorphonuclear neutrophils; PMNs), non-phagocytic lymphocytes (mouse thymocytes), and non-functional leukocytes (mouse leukemia L1210 cells) . When antibiotics bound to PMNs, they bound about the same to L1210 cells but much less to thymocytes . Combining these data with previous data, the ranking of cells that bound the greatest amount of antibiotics was: PMNs = L1210 cells = blood mononuclear leukocytes greater than thymocytes greater than erythrocytes . Thus, antibiotics bind differentially and not indiscriminately to mammalian cells. Vutr Boles, 1986, 25(6), 86 - 91 {Pharmacokinetics of the cephalosporin antibiotic cefotiam following its intravenous administration to patients after cholecystectomy}; Terziivanov D et al.; The pharmacokinetic behaviour of cephalosporin antibiotic, second generation after intravenous administration to patients during the early post-operative period was characterized as well as after cholecystectomy . The data suggest a two-compartment distribution with elimination from the central compartment, realized on account of the renal way of clearance . In one of the patients, with one-compartment distribution of the drug, the presence of the theoretical determining factors in "the collapse" of one two-compartment open model to one-compartment is shown, associated with clinical characteristics of that patient. Scand J Infect Dis Suppl, 1986, 49, 175 - 81 Antibiotic policy; Williams JD; Antibiotics are often effective in curing a patient of his infection even when used in a suboptimal manner . In this situation it is often difficult for the prescriber to accept that he/she is using antibiotics "badly" when he can point to the majority of his infections responding well--either to the antibiotic or the patient's own immune response . Many attempts have been made to limit antibiotic use by selective laboratory reporting, by restricting the antibiotics available, by producing guidelines for initial therapy of infection or prophylaxis, by involvement of infectious disease specialists in all antibiotic use and by several other systems . It appears, however, that antibiotic use is still heavily criticised and is a continuing source of conflict in medicine . Consensus on antibiotic indications is still difficult to obtain and is likely to be achieved very slowly . It is clear that polemic is not sufficient and that consensus practices can only be based upon firm scientifically acquired data and detailed discussion of the options by those most intimately involved. Infection, 1986, 14 Suppl 4, S270 - 3 Further methodological improvement in antibiotic bone concentration measurements: penetration of ofloxacin into bone and cartilage; Wittmann DH et al.; Ten patients (mean age 63 years) undergoing alloarthroplastic hip joint replacement received 400 mg ofloxacin orally before anaesthesia . Venous blood samples were obtained before administration of the drug and then at intervals of up to 24 h . Bone samples were taken from femoral head and femoral shaft . Antibiotic concentrations were assessed by means of HPLC . The maximum serum concentration was 3.45 mg/l on average, after 90 min, and the maximum average bone concentration was 1.22 mg/l after 270 min . The half-life of ofloxacin in bone was shorter than that in serum . The concentrations measured in bone were superior to the minimal inhibitory concentrations reported for most pathogens of bone and joint infections . Therefore ofloxacin appears to be a valuable contribution to the therapeutic options of oral treatment for bone and joint infections. Leuk Res, 1986, 10(10), 1233 - 9 Induction of erythroid differentiation by the anthracycline antitumor antibiotics, aclacinomycin A, musettamycin and marcellomycin; Steinheider G et al.; The oligosaccharide anthracycline aclacinomycin A is of considerable clinical interest since, in comparison to adriamycin and daunomycin, the compound exhibits reduced cardiac toxicity and is devoid of mutagenicity/carcinogenicity . In addition, induction of differentiation in the human promyelocytic leukemia cell line HL 60 and possibly in one case of human acute myeloblastic leukemia by aclacinomycin A has been observed . Our data indicate that aclacinomycin A and related compounds, such as musettamycin and marcellomycin, are extremely potent inducers of differentiation in mouse (Friend leukemia cells, clone F4-6), rat (rat erythroleukemia, clone D5A1), and human erythroid cell lines (K 562 cell line) and that the relative inductive potency of marcellomycin and musettamycin, in general, is higher than that of aclacinomycin A . This potency difference may be due to the presence of a Cl-hydroxyl group in the aglycone of the marcellomycin and musettamycin molecule . Thus, oligosaccharide anthracyclines are a new class of inducers of erythroid differentiation . The high potency of these compounds, the possibility to study structure-activity relationships relative to their inductive potency and the fact that they induce erythroid differentiation in cells of different species as well as granulocytic differentiation in human cells should facilitate the study of basic mechanisms of hemopoietic differentiation . In addition, the therapeutical significance of these anthracycline effects should be investigated by studying, comparatively, the differentiation-inducing and antitumor effects of these compounds in primary leukemic cell cultures from patients. Czech Med, 1986, 9(4), 187 - 90 Comparison of serum and coagulum antibiotic levels with respect to protected blood coagulum; Moravek J et al.; Serum and coagulum antibiotic levels have a parallel course . Coagulum antibiotic concentrations are more than ten times lower than serum concentrations . Therefore the optimal dosage of perioperative infusion should be high enough to establish steady state by means of sufficiently high serum levels . Antibiotics capable of attaining high serum levels and having a long half-life are best suited for the formation of effective antibiotic concentrations in blood coagulum . This is particularly true for cephalosporins and penicillins . Aminoglycoside antibiotics are not recommended for the formation of protected coagulum . "Ceftriaxon in the treatment of Severe bacterial infections". Eur J Clin Pharmacol, 1986, 30(4), 503 - 4 Acceptance of antibiotic mixtures by infants and children; Uhari M et al.; The acceptance by children of two pharmacologically identical phenoxymethyl-penicillin potassium and erythromycin ethylsuccinate mixtures, differing only in their flavouring agents, was compared in a randomised blind manner . The time a nurse required to give the drug to a child was recorded and a score of the acceptance was given by the nurse . The mean time to give erythromycin Brand 1 was 29 s (SD +/- 21, number of children = 20) and mean time to give Brand 2 it was 16 s (SD +/- 13, n = 18); the difference was significant (p less than 0.05) . The mean scores were 2.9 (SD +/- 0.6) and 3.4 (SD +/- 0.5), difference -0.5 (p less than 0.025) . The difference between the two penicillin products was not significant . The time required to give a medicine was a useful way to compare the effect of different flavouring mixtures on the acceptance of drugs by infants and children. Chemotherapy, 1986, 32(4), 374 - 8 Absence of effects on platelet membrane fluidity by antibiotics in ESR spectra; Sakata S et al.; The effect of several antibiotics on rat platelet membrane fluidity was examined by ESR spectrometry using 5-doxyl stearate as the spin probe . Latamoxef, cefamandole, cefotaxime and carbenicillin had negligible effects on the order parameters, the indices of membrane fluidity, of platelet-rich plasma or washed platelets at high concentrations that would inhibit ADP-induced rat platelet aggregation in vitro . A further in vivo study with one of these antibiotics, latamoxef, showed no significant effect on the fluidity based on ESR data. Zh Nevropatol Psikhiatr Im S S Korsakova, 1986, 86(4), 496 - 9 {Peripheral neuropathies caused by antibiotics during their production and administration}; Gerasimova MM et al.; The authors consider the clinical picture and pathogenesis of damage to the peripheral nervous system in patients suffering from occupational disease induced by exposure to antibiotics . In clinical terms it is most often manifested in sensory polyneuropathy and less frequently in isolated damage to neural stems (facial, auditory, sciatic, external femoral skin nerves) . Allergic vasculitis due to exposure to antibiotics is responsible for this pathology of the peripheral nervous system. Med Pr, 1986, 37(6), 383 - 7 {Occupational allergy to antibiotics}; Rudzki E et al.; Of 57 nurses suffering from dermatitis and having occupational contact with antibiotics 37 per cent exhibited positive tests with these drugs . Analogous figures for pharmaceutical industry workers were 34 subjects and 41 per cent and for veterinary surgeons 31 subjects and 29 per cent . A case of an ophthalmist sensitive to dethreomycin under occupational conditions was also recorded . Furthermore, six nurses exhibited inhalant allergy to penicillin manifested clinically by an anaphylactic shock or urticaria or, in two cases, by contact urticaria: one also due to penicillin and the other due to streptomycin. Drugs Exp Clin Res, 1986, 12(6-7), 495 - 505 Molecular mechanism of novel DNA sugar damage by an antitumour protein antibiotic; Goldberg IH et al.; Neocarzinostatin (NCS) belongs to a family of antitumour protein antibiotics that selectively inhibit DNA synthesis . Replicon initiation in mammalian cells is selectively inhibited by NCS, and cells defective in DNA repair, such as ataxia telangiectasia fibroblasts, are especially sensitive to NCS as they are to X-ray . The holoantibiotic consists of a nonprotein chromophore (Mr = 659), tightly and specifically bound to an apoprotein (Mr = 10,700) . The apoprotein protects the highly labile chromophore from degradation in aqueous solution; all the activity resides in the nonprotein chromophore . The latter binds specifically to DNA, especially to regions rich in T and A residues, with a tight binding site consisting of four base pairs . NCS chromophore consists of three main structural subunits: a naphthoic acid derivative, an amino-sugar and a connecting highly unsaturated middle component (C12H5) with a strained ether (probably epoxide) and cyclic carbonate . The authors have proposed that the naphthoic acid subunit intercalates DNA and the positively charged amino sugar binds electrostatically to the negatively charged sugar phosphate backbone of DNA; these two anchors serve to juxtapose the middle piece with the deoxyribose of mainly thymidylate residues in DNA . Upon activation of the drug by a thiol (which forms an adduct with the middle piece) and in the presence of O2, there is a selective oxidation of the 5'-C of deoxyribose to produce a DNA strand break with a phosphate at the 3'-end and a nucleoside 5'-aldehyde at the other . Kinetic analysis shows that one molecule of thiol adds to DNA-bound NCS chromophore even in the absence of oxygen; this is rapidly followed by the consumption of 1 mol of O2 and then another mol of thiol . The oxygen of the 5'-aldehyde is derived from O2, not H2O . Even in the absence of O2 the NCS chromophore abstracts a hydrogen from C-5' of deoxyribose in DNA, presumably generating a carbon-centred radical intermediate in the DNA (other mechanisms have not been eliminated) which can add O2 to form a peroxy derivative . The second molecule of thiol may be involved in the cleavage of this complex to form the 5'-aldehyde at the strand break . There is no evidence for the involvement of metals or a diffusible form of reduced oxygen.(ABSTRACT TRUNCATED AT 400 WORDS) Ann N Y Acad Sci, 1986, 468, 329 - 38 Flow cytometry of bacteria: cell cycle kinetics and effects of antibiotics; Steen HB et al.; Flow cytometric determination of the DNA and protein content of E . coli has been carried out by means of a microscope-based flow cytophotometer with a high pressure arc lamp excitation ligh source . Fluorescence (DNA)/light scatter (total cell protein) dual parameter histograms with a resolution cv of 5% were obtained for cells labeled with a combination of mithramycin and ethidium bromide . Histograms of E . coli in rapid and slow exponential growth are presented to exemplify how the cell cycle kinetics of bacteria can be studied in much more detail than has been possible by other methods . Significant effects of chloramphenicol and penicillin on the cell cycle distribution and cell numbers of E . coli cultures were evident after one hour of culture . The data provided information on which parts of the cell cycle and what types of processes were affected by the drug . It appears that flow cytometry may become a valuable tool in studies of the cell cycle of bacteria as well as in clinical drug testing. Dev Toxicol Environ Sci, 1986, 14, 81 - 9 Evaluation of potential nephrotoxicity of antibiotics; Koiso K et al.; In order to assess the potential nephrotoxcity excerted by various antibiotics in therapeutic doses, the effects of antibiotics administered to Wistar rats in vitro and in vivo were investigated in terms of protein synthesis, nucleic acid metabolism, and lysosome stability . In vivo experiment protein synthesis was inhibited by SM, KM, GM and CL . RNA metabolism and stability of lysosomal enzyme, acid-phosphatase, were also disturbed by the aminoglycosides . In vitro experiments yielded almost the same tendencies . In our studies cephalosporins and related antibiotics had no influence upon the metabolism of