Postgrad Med, 1982 Jul, 72(1), 215 - 8 Lung abscess: back for an encore? Cohen DJ. The rise in incidence of lung abscess due to opportunistic organisms has reemphasized the need for early recognition and treatment . Opportunistic organisms can cause lung abscess in immunocompromised hosts . Most lung abscesses are primary, occurring as a result of aspiration of oral contents into the dependent portions of the lung in persons with dysphagia or decreased consciousness . Symptoms of lung abscess include productive cough, fever, leukocytosis, weight loss, and putrid sputum . Among the complications are progression to a chronic stage, empyema, massive hemoptysis, metastatic brain abscess, and bronchopleural fistula . Treatment of lung abscess is primarily medical, consisting of an appropriate antibiotic regimen and chest physical therapy . Surgery is reserved for unresponsive patients or those with complications. Laryngoscope, 1982 Jul, 92(7 Pt 1), 729 - 31 The role of high resolution computerized tomography and standardized ultrasound in the evaluation of orbital cellulitis; Goodwin WJ Jr et al.; We reviewed the records of 22 patients with orbital cellulitis to determine the value of high resolution computerized tomography (HRCT) and standardized ultrasound (US) in their management . In 13 patients, they demonstrated abscess formation and accurately defined its location and extent . The appearance of an abscess did not necessarily mandate immediate surgery . Three patients responded promptly to intensive antibiotic therapy and resolved despite a presumptive diagnosis of orbital abscess . The remaining 10 patients required surgical intervention and abscess formation was confirmed . In patients presenting with good visual acuity and some globe motion we recommended instituting intensive intravenous antibiotic therapy for 36 hours with close monitoring of visual acuity, avoiding surgery unless some impairment of vision is noted . The decision regarding surgery is then made on the time honored basis of response to therapy . Surgery is no necessary in those patients exhibiting prompt significant improvement in local inflammatory signs. Clin Pharmacol Ther, 1982 Jul, 32(1), 113 - 21 Unidirectional absorption of gentamicin from the peritoneum during continuous ambulatory peritoneal dialysis; Somani P et al.; Gentamicin kinetics were determined after intravenous or intraperitoneal injection in five patients undergoing continuous ambulatory peritoneal dialysis (CAPD) . Our objective was to determine rate of absorption of gentamicin from the peritoneum into the systemic circulation and vice versa . After intraperitoneal instillation of 1 mg/kg in the CAPD fluid during a 6-hr dwell time, the antibiotic appeared in the serum within 15 min in four of five patients . Peak serum concentrations ranged between 1.6 and 7.2 mg/l(mean +/- SD = 3.52 +/- 2.22) in all five patients and the time to reach peak concentration was 3.8 +/- 1.5 hr . Peritoneal gentamicin clearance was 13 ml/min . Percent extraction of gentamicin from the PD fluid within the 6 hr of intraperitoneal exposure ranged from 65% to 100% (mean +/- SD = 86.8 +/- 13.2) . The fraction of the intraperitoneal dose absorbed into systemic circulation was found to be 0.84 independently by calculating the ratio of AUCip and AUCiv . When the same dose of gentamicin was injected intravenously (1 mg/kg), no gentamicin could be detected in the peritoneal fluid in three of five patients and only a very small amount of the drug was present for a brief period of time in the remaining two . The kinetic parameters of intravenous gentamicin were: volume of distribution, 0.3 l/kg; elimination rate constant, 0.028 hr(-1), plasma clearance 0.009 l/kg . min(-1), and half-life 27.4 hr . In two patients with acute peritonitis treated with intraperitoneal gentamicin, peak serum concentrations were found to range between 3.5 and 4.5 mg/l . These data suggest that gentamicin is rapidly absorbed from the peritoneal fluid into the blood compartment, but that occurrence of the reverse exchange is negligible . Thus, CAPD would not be expected to alter the elimination characteristics of intravenous gentamicin . Instillation of gentamicin in CAPD fluid may allow rapid absorption to reach therapeutic serum concentrations. Cancer Res, 1982 Jul, 42(7), 2821 - 8 Mechanism of interaction of CC-1065 (NSC 298223) with DNA; Swenson DH et al.; CC-1065 (NSC 298223), a potent new antitumor antibiotic produced by Streptomyces zelensis, interacts strongly with double-stranded DNA and appears to exert its cytotoxic effects through disruption of DNA synthesis . We undertook this study to elucidate the sites and mechanisms of CC-1065 interaction with DNA . The binding of CC-1065 to synthetic and native DNA was examined by differential circular dichroism or by Sephadex chromatography with photometric detection . The binding of CC-1065 with calf thymus DNA was rapid, being complete within 2 hr, and saturated at 1 drug per 7 to 11 base pairs . The interaction of CC-1065 with synthetic DNA polymers indicated a specificity for adenine- and thymine-rich sites . Agarose gel electrophoresis of CC-1065-treated supercoiled DNA showed that CC-1065 did not intercalate . Site exclusion studies using substitutions in the DNA grooves showed CC-1065 to bind primarily in the minor groove . CC-1065 did not cause DNA breaks; it inhibited susceptibility of DNA to nuclease S1 digestion . It raised the thermal melting temperature of DNA, and it inhibited the ethidium-induced unwinding of DNA . Thus, in contrast to many antitumor agents, CC-1065 stabilized the DNA helix . DNA helix overstabilization may be relevant to the mechanism of action of CC-1065. Br J Clin Pharmacol, 1982 Jul, 14(1), 31 - 42 The third S.K . & F . Prize lecture, University of London, December 1981 . The clinical pharmacology of oral contraceptive steroids; Orme ML; PIP: This document attempts to fill in some gaps with regard to the clinical pharmacology of oral contraceptives (OCs) . The total dose level cannot be reduced much further without impairing the contraceptive efficacy of the drug . Plasma concentration of steroids varies widely from individual to individual . The bioavailability of norethisterone and ethinyl estradiol (EE) is incomplete when drugs are given orally as opposed to intravenously . Reduced norethisterone bioavailability is due to a 1st pass effect; drugs may undergo 1st pass elimination either in the gut wall or in the liver . With EE, the values of EE sulphate were higher when EE was administered orally than when it was given intravenously . This suggests that after oral dosing, a significant part of the 1st pass effect is due to sulphate conjugation in the gut wall . Norethisterone and levonorgestrel are extensively bound to albumin and sex hormone binding globulin in plasma . This binding capacity can be enhanced by EE and drugs such as phenobarbitone . EE is also bound to albumin . While OC therapy may interfere with the activity of the other drug treatment given at the same time, this is not clinically of major importance . OCs may diminish the effects of anticoagulants, of oral hypoglycemic drugs, or of antihypertensive drugs . Likewise, the effect of OCs may be altered by the simultaneous administration of other drugs . It is also apparent that the effect of OCs may be enhanced by vitamin C . Rifampicin, a potent inducer of hepatic microsomal drug metabolizing enzymes, does diminish the efficacy of OCs . Anticonvulsants and antibiotics are also in the same category . The interaction between OCs and antibiotics is probably the most controversial of all . There have been reports in the literature about women who have become pregnant while taking OCs and antibiotics . It is likely that the majority of women are not at risk of contraceptive failure when using a broad spectrum antibiotic at the same time as the OC . Am J Trop Med Hyg, 1982 Jul, 31(4), 857 - 8 Strongyloides infection and meningitis in an immunocompromised host; Vishwanath S et al.; Strongyloidiasis and aseptic meningitis occurred in a renal transplant recipient who was receiving immunosuppressive drugs . Cure followed therapy with antibiotic administration for 3 days combined with oral thiabendazole, suggesting parasitic infection as the most likely cause of meningitis . Awareness of this disease and need for prompt institution of therapy is stressed . Prophylactic administration of thiabendazole is probably preventive. HNO, 1982 Jul, 30(7), 272 - 4 {The treatment of the otseroma with human biologic glue}; Brusis T; The use of human biologic glue makes an optimal adaptation of the loosened superficial skin of the ear and an exact restoration of its profile possible . Traumatising mattrass suture can be avoided . An antibiotic therapy and a clinical treatment are unnecessary . In addition this study contains a tabulation of the up to now known indications for the use of human biologic glue in ENT. Am J Med, 1982 Jul, 73(1), 63 - 70 Combined neutrophil and T-cell deficiency: initial report of a kindred with features of the hyper-IgE syndrome and chronic granulomatous disease; Robinson MF et al.; A six year old female presented with a recent history of pyoderma gangrenosum involving her legs and arms associated with an episode of Mycoplasma-like pneumonia . This was followed by Aspergillus osteomyelitis involving her left ulna and right femur . Both the skin lesions and the osteomyelitis responded to prolonged treatment with antifungal and antibiotic agents . Investigation of this patient revealed (1) an elevated serum IgE (4,800 units/ml), (2) defect in neutrophil chemotaxis that appeared to be due to immune complexes, (3) an abnormal nitroblue tetrazolium (NBT) result (0 percent stimulated and unstimulated), and (4) depressed mitogen responses to concanavalin A, phytohemagglutinin, and pokeweed mitogen, negative results of intradermal skin tests, and negative dinitrochlorobenzene (DNCB) sensitization . The patient's clinically unaffected sibling had similar findings except for a positive DNCB response . In both children, intracellular bacterial killing of catalase-positive and negative organisms was normal . Kindred studies revealed widespread T-cell abnormalities consistent with autosomal dominant inheritance . Tissue typing studies showed that affected siblings shared the A1, B8, DR3 haplotype . This kindred is unique in that both the proband and the sibling have abnormalities of both the hyper-IgE syndrome and chronic granulomatous disease. Cancer Res, 1982 Jul, 42(7), 2651 - 5 Structure-activity relationships for the induction of differentiation of HL-60 human acute promyelocytic leukemia cells by anthracyclines; Schwartz EL et al.; Marcellomycin, a newly developed anthracycline antibiotic with antineoplastic activity, was tested as an inducer of differentiation of the human promyelocytic leukemia cell line HL-60 in vitro . The percentage of cells reducing nitro blue tetrazolium, an indication of a stimulus-induced respiratory burst typical of mature phagocytes, was used as a functional measure of the extent of differentiation . Marcellomycin was a potent inducer of maturation, with 95% of the cells expressing a terminally differentiated state after 10 days of exposure to a concentration of 40 nM anthracycline . Cells exposed to marcellomycin exhibited a 35-fold increase in their total superoxide anion-generating capacity, an 80% increase in acid phosphatase activity, and a loss of myeloperoxidase and chloroacetate esterase activities . In addition, marcellomycin-treated cells stained negatively for alpha-naphthyl acetate esterase . These findings provided evidence for the granulocytic nature of the mature cells . In contrast, marcellomycin was not an effective inducer of differentiation of Friend murine erythroleukemia cells . Studies on the relationship between structure and the ability to induce differentiation of HL-60 leukemia cells demonstrated that removal from the marcellomycin molecule of the terminal 2-deoxyfucose (musettamycin) or its substitution by cinerulose (aclacinomycin A) did not alter differentiation-inducing capacity . However, removal of the carbomethoxy group from the C-10 position of marcellomycin substantially reduced its potency as an initiator of maturation, and removal of the two terminal 2-deoxyfucose moieties (pyrromycin) decreased both potency and the maximal percentage of differentiated cells produced in the population . The monosaccharide anthracyclines Adriamycin and carminomycin were completely inactive as inducers of HL-60 leukemia cell maturation . The results suggest that certain anthracyclines would be reasonable candidate drugs to use in a clinical trial aimed at reducing the leukemic stem cell burden through maturation rather than through cytodestruction. Obstet Gynecol, 1982 Jul, 60(1), 30 - 4 The clinical diagnosis of trichomoniasis; McLellan R et al.; Two hundred twenty-six consecutive women attending an inner-city clinic for sexually transmitted diseases were evaluated . Problem-directed histories and physical examinations were conducted and vaginal specimens for wet preparation and Trichomonas vaginalis culture were obtained from each patient . One hundred patients were found to be infected . Patients with multiple sex partners were found to be at increased risk of trichomoniasis (P less than .05) . Those with abnormal discharge noted on examination had a higher frequency of positive cultures for T vaginalis (P less than .001) . Only 50% of patients with trichomoniasis had an abnormal discharge . Patients with greater than 10 white blood cells per high power field on wet preparation, regardless of whether trichomonads were visualized, had a higher incidence of trichomoniasis (P less than .01) . Factors that were not associated with Trichomonas infection included patient age, frequency of coitus, date of most recent coitus, day of menstrual cycle on which patient was examined, recent antibiotic use, use of contraceptives or specific contraceptive methods, symptoms of discharge or pruritus, or the finding of Leptothrix on wet preparation . These data support the contention that the classic description of trichomoniasis cannot be uniformly relied upon for diagnosis, but that patients with multiple sex partners, abnormal vaginal discharge and/or greater than 10 white blood cells per high power field on wet preparation are at increased risk of infection by T vaginalis. Mol Biol (Mosk), 1982 Jul-Aug, 16(4), 857 - 64 {Role of spot gene product in the degradation of pppGpp in bacteria}; Belitskii BR et al.; In Baccillus subtilis cells, in contrast to Escherichia coli cells, chelating agent 1,10-phenanthroline induces the expansion of guanosine-5'-diphosphate,3'-diphosphate( (ppGpp) pool, as well as the pool of its precursor guanosine-5'-triphosphate,3'-diphosphate (pppGpp) . Under these conditions the degradation rate of both nucleotides decreases greatly, which is the main cause of their accumulation in the cells . In E . coli phenanthroline inactivates the product of spoT gene, which is responsible for ppGpp degradation, as a result of combining Mn2+ ions necessary for the activity of this enzyme . The addition of Mn2+ ions to B . subtilis cells, treated with phenanthroline, leads to the decline in (p)ppGpp pools . Antibiotic tetracycline, which has the chelating properties at the concentration of 1 mg/ml, also inactivates spoT gene product in E . coli and slows down the decay of ppGpp, but not of pppGpp . The addition of high concentrations of tetracycline to B . subtilis cells leads to severe inhibition of the degradation of both nucleotides . Therefore in B . subtilis spoT gene product is involved in the degradation of pppGpp, as well as ppGpp . In E . coli cells with defective gpp gene product, taking part in the conversion of pppGpp to ppGpp, phenanthroline and tetracycline also inhibit the breakdown of both nucleotides . The similarity of B . subtilis and E . coli gpp cells in respect of spoT gene product functions and of enhanced pppGpp fraction in the total amount of guanosine polyphosphates during aminoacyl-tRNA limitation makes it plausible that in B . subtilis cells the product of gpp gene is missing or has low activity. J Biochem (Tokyo), 1982 Jul, 92(1), 7 - 12 Mechanism of action of cerulenin on fatty acid synthetase . Effect of cerulenin on iodoacetamide-induced malonyl-CoA decarboxylase activity; Kawaguchi A et al.; Cerulenin, an antibiotic with the structure of (2R)(3S)-2,3-epoxy-4-oxo-7,10-dodecadienoylamide, irreversibly inactivates yeast fatty acid synthetase . Of all catalytic activities of the synthetase, only the condensation reaction is inhibited by cerulenin . At 0 degrees C and pH 6.5, the second-order rate constant of k = 88 M-1 . S-1 was obtained for the inactivation by cerulenin . This value was about 90-times greater than the rate constant for the inactivation of the enzyme by iodoacetamide . The enzyme was protected against the action of cerulenin by prior treatment with acetyl-CoA but not malonyl-CoA . Treatment of the enzyme with iodoacetamide, while impairing the synthetase activity, induced malonyl-CoA decarboxylase activity {Kresze, G.-B., Steber, L., Oesterhelt, D., and Lynen, F . (1977) Eur . J . Biochem . 79, 191-199} . Cerulenin had no effect on the malonyl-CoA decarboxylase activity of the iodoacetamide-treated enzyme . N-Ethylmaleimide, in contrast, inhibited the iodoacetamide-induced malonyl-CoA decarboxylase activity . When the enzyme was preincubated with cerulenin, malonyl-CoA decarboxylase activity could not be detected even after treatment of the enzyme with iodoacetamide . These results indicated that the reaction of cerulenin with the peripheral SH-groups of the synthetase is responsible for the inactivation. Dermatologica, 1982 Jul, 165(1), 62 - 5 Oral treatment of acne vulgaris and oil acne with tetracycline; Czernielewski A et al.; In 51 patients with acne vulgaris and 34 patients suffering from occupational oil acne the clinical effect of orally administered tetracycline was evaluated before, during and after a 3-monthly treatment (total dose of antibiotic: 1st month, 28.5 g; 2nd and 3rd months, 15.0 g) . Patients treated with placebo were used as controls . Investigations of the skin fluorescence under Wood's light were performed during the treatment period . In one half of the patients with acne vulgaris and oil acne oral treatment with tetracycline had a very good clinical effect . The purpose of this investigation was the comparison of the results of the treatment of acne vulgaris and occupational oil acne with tetracycline. Cancer Res, 1982 Jul, 42(7), 2779 - 85 Bleomycin and talisomycin sequence-specific strand scission of DNA: a mechanism of double-strand cleavage; Mirabelli CK et al.; Computer analyses of DNA sequencing data obtained using various restriction fragments of pBR 322 DNA indicate that a trinucleotide sequence (-Pyr-G-C-) is the most preferred site for cleavage by the antitumor antibiotic bleomycin A2 . Talisomycin A, a structurally related bleomycin analog, cleaved at the sequences -G-T/A- most preferentially . However, the presence of a pyrimidine at the 5' side of guanine at the cleavage site did not increase the probability of that site being cleaved by talisomycin . Using denaturing and nondenaturing polyacrylamide gel analyses of the drug-DNA reaction products . The sites of both single- and double-strand breaks have been localized and differentiated . The results indicate that a major determinant for location of a site-specific double-strand break is the production of two closely spaced sequence-specific single-strand breaks by the drugs on opposite strands of the DNA . A four-base pair sequence is proposed for the optimal sequence for bleomycin-induced double-strand breaks. Life Sci, 1982 Jun 28, 30(26), 2309 - 15 The effect of gentamicin on calcium uptake by renal mitochondria; Sastrasinh M et al.; The effect of the nephrotoxic aminoglycoside antibiotic, gentamicin, on calcium uptake by renal cortical mitochondria was assessed in vitro . Gentamicin was found to be a competitive inhibitor of mitochondrial Ca++ uptake . This effect displayed a dose response with a Ki of 233 microM and occurred at gentamicin concentrations below those that inhibit mitochondrial electron transport . These results further demonstrate the potential for gentamicin to alter membrane function and thereby contribute to toxic cell injury via its interactions with divalent cations. Br Med J (Clin Res Ed), 1982 Jun 19, 284(6332), 1827 - 9 Treatment of acute abscesses in the casualty department; Simms MH et al.; In the treatment of acute pyogenic soft-tissue abscess incision, curettage, and primary suture was compared with incision and drainage alone in a randomised prospective trial . Operations were performed under antibiotic cover by casualty officers, and patients were reviewed by an independent observer in a septic dressing clinic . Altogether 114 patients were studied, of whom 54 were treated by curettage and primary suture and 60 by simple drainage . The mean healing time was 8.9 days in those treated by primary suture and 7.8 days in those treated by simple drainage (p less than 0.05) . Primary healing failed to occur in 19 (35%) of the sutured wounds, but there were no other complications in either group . It is concluded that incision and drainage alone is adequate treatment for acute soft-tissue abscess. Mycopathologia, 1982 Jun 18, 78(3), 141 - 3 Gastrointestinal inoculation of Sporothrix schenckii in mice; Kennedy MJ et al.; Antibiotic-decontaminated and untreated conventional mice were inoculated intragastrically with 10(7) viable cells of Sporothrix schenckii to compare the incidence of gastrointestinal (GI) colonization . In control mice, S . schenckii was completely eliminated from the GI tract by 12 h post-inoculation . Antibiotic-treated mice also failed to become colonized with this fungus, however, higher population levels of Sporothrix cells remained in the GI tract for a longer period of time before being eliminated . The ability of S . schenckii to disseminate from the lumen of the bowel to infect other organs was also tested . Results indicate that the gastrointestinal tract is not a portal of entry into the host for S . schenckii. Med J Aust, 1982 Jun 12, 1(12), 499 - 502 Intracranial aerocele in facial injury; Pitt TT; Aspects of intracranial aerocele are described and exemplified by two cases which presented to the Plastic Surgery Unit . Austin Hospital, Melbourne, as radiological findings incidental to facial injury . The first case illustrated the occasional problem of identifying the site of dural tear; a fracture could not be identified on X-ray film or at operation, and this can make subsequent dural repair more difficult . The second case was associated with florid clinical signs of facial fractures which were supported by X-ray findings . Both patients underwent surgery for the primary injury, and received prophylactic therapy with antibiotic agents because of the risk of meningitis associated with dural tears . In neither case did intracranial air persist beyond 14 days; therefore, dural repair was not performed . It is important to look for evidence of dural damage when dealing with facial injury either in the casualty or in the subsequent management of the patient. J Biol Chem, 1982 Jun 10, 257(11), 6207 - 16 Reaction of anthramycin with DNA . Biological consequences of DNA damage in normal and xeroderma pigmentosum cell; Petrusek RL et al.; Anthramycin, an antitumor antibiotic produced by Streptomyces refuineus, produces a well defined covalent adduct with DNA and lies within the narrow groove of DNA, attached through a thermal-labile covalent animal linkage to the exocyclic amino group of guanine, without detectable distortion of the helix (Petrusek, R . L., Anderson, G . L., Garner, T . F., Fannin, Q . L., Kaplan, D . J . Zimmer, S . G., and Hurley, L . H . (1981) Biochemistry 20, 1111-1119) . This paper described results in which the biological consequences of DNA damage and repair by repair-proficient and a repair-deficient xeroderma pigmentosum (XP 12RO) cell line are presented . Anthramycin has been shown to produce excision-dependent single and double strand breaks in DNA, both of which appear to persist many hours after removal of the drug from the media . The lower ability of the xeroderma pigmentosum cell line to remove ability of the xeroderma pigmentosum cell line to remove anthramycin lesions from DNA is correlated with a decreased cell survival . The biological consequences of DNA damage (genetic effects, DNA strand breakage, and cytotoxicity) are discussed with respect to the defined structure and stability of the anthramycin-deoxyguanosine adduct. Biochemistry, 1982 Jun 8, 21(12), 3006 - 13 Altered physiochemical properties of the deoxyribonucleic acid-mitomycin C complex . Evidence for the conformational change in deoxyribonucleic acid; Kaplan DJ et al.; Binding of the antibiotic mitomycin C to sonicated calf thymus DNA results in increased viscosity and an unaltered sedimentation constant of DNA . Flow dichroism measurements of the mitomycin C-DNA complex indicate that the 310-nm absorbance vector of the chromophore of the bound drug is oriented at approximately 57.2 degrees relative to the helix axis . A conclusion drawn from these results is that mitomycin C does not intercalate between base pairs, but rather, it is bound in one of the grooves . Binding of mitomycin C causes a number of changes which are DNA size dependent: (1) increased viscosity of sonicated, decreased viscosity of nonsonicate DNA; (2) unaltered sedimentation rate of sonicated, increased rate of nonsonicated DNA; (3) reduced electrophoretic mobility of nonsonicated DNA; (4) electron microscopic appearance of sonicated DNA-mitomycin complexes which is similar to that of control, while nonsonicated DNA complexes which display highly coiled, looped structures not seen in control nonsonicated DNA . These size-dependent effects are interpreted as indicative of conformational distortion of DNA at rare intervals, caused by a minor fraction of total bound mitomycin . The parallel used of sonicated and nonsonicated DNA as probes for certain effects of drug binding may be useful for detecting this type of phenomenon in general. Biochim Biophys Acta, 1982 Jun 4, 704(2), 186 - 96 Solution and ion-complexed conformations of beauvericin determined by proton magnetic resonance spectroscopy; Khaled MA et al.; The conformational properties of the cyclohexadepsipeptide antibiotic Beauvericin have been investigated by 1H-NMR spectroscopy in polar (C2H3O2H) and non-polar (CCl4, C62H6, C2HCl3) solvents and in two solvent mixtures; one a mixture of a polar and non-polar solvent (C2H3O2H/CCl4) and the other an aromatic solvent in a non-polar environment (C62H6/CCl4) . The ion-complexation properties of Beauvericin with alkali metal halides (Li+, Na+, K+, Cs+) have also been studied . It is demonstrated that changes in chemical shifts of Beauvericin with concentration, with polarity of solvent or with added alkali metal ion reflect changes not only in the solvent properties but also changes in backbone conformation and changes due to ion-complexation, where appropriate, and therefore cannot be used, by themselves, to determine the conformation of the molecule, its self-aggregation properties, or the stoichiometry of the metal ion-complex . The backbone conformations of Beauvericin in different environments are determined by methods that are independent of chemical shift analysis; i.e., by measurements of 5J(HH) magnitudes observed between the alpha-CH protons of the L-phenylalanine and D-hydroxyisovaleric acid (DHyIv) residues and by nuclear Overhauser effect measurements observed between alpha-CH(HyIv) and (N)-CH3(Phe) proton signals . In the knowledge of these results the chemical shifts of Beauvericin in different environments can then be rationalised . It is found that the conformation of Beauvericin in a polar solvent is different from that found in a non-polar solvent and from that found for the in the ion-complexed form is similar to that found in non-polar solvents . By taking into account the conformational properties of the L-phenylalanine and DHyIv side-chains, it is possible to assign unambiguously the magnetically non-equivalent beta-CH2(Phe) and gamma Me(HyIv) proton signals and so elucidate the complete conformational behaviour of the uncomplexed forms of Beauvericin in a polar and a non-polar environment, and of the ion-complexed form of Beauvericin in a polar solvent. Food Chem Toxicol, 1982 Jun, 20(3), 289 - 300 Patulin mycotoxicosis in the rat: toxicology, pathology and clinical pathology; McKinley ER et al.; Patulin, a secondary metabolite produced by species of the genera Penicillium and Aspergillus, was administered to male Sprague-Dawley rats, weighing 50-60 g, by the oral, sc and ip routes . The 72-hr LD50 values (in mg/kg weight) were: oral, 55.0; sc, 11.0; ip, 10.0 . Mortality was greatest 0-24 hr after administration by the oral and sc routes and 49-72 hr after ip dosing . Gross alterations consisted of gastric and intestinal hyperaemia and distention . Histopathological alterations consisted principally of ulceration and inflammation of the stomach . Patulin was administered orally to rats daily or every other day for 2 wk at doses of 50 or 75% of the oral LD50 . Mortality in the treated groups was greater than in controls but was similar for all treated groups . No evidence of cumulative toxicity was found and the gross and histopathological alterations were similar to those found in the LD50 studies . Clinicopathological alterations included metabolic alkalosis with respiratory compensation, oliguria, decreased serum sodium, elevated blood glucose, reduced plasma protein and an elevated total leucocyte count which differential leucocyte counts indicated to be due to neutrophilia . The inflammatory alterations observed in the gastro-intestinal tract may be due to the irritant properties of patulin or to an alteration in the gastro-intestinal flora by the antibiotic activity of patulin. Cent Afr J Med, 1982 Jun, 28(6), 129 - 31 Treatment compliance and outcome at an urban primary care clinic; Axton JH et al.; PIP: An attempt was made to determine treatment compliance and outcome at an urban promary care clinic in Zimbabwe . A research nursing sister sat in on an urban primary care clinic 1 day a week for 10 consecutive weeks recording the address, presenting compliant, physical findings, and treatment ordered, as defined by the clinic sister in attendance, of the first 10 consecutive cases seen on the day of the visit . Approximately 1 week later, she visited the home address and interviewed the mother . It is only possible to give medication for 24 hours at a time in the urban clinics, which entails a daily visit by the mother and child, even for oral medicines . At a child's 1st visit to the clinic, the mother is given a treatment card on which daily attendance, with medication given, ir recorded . Compliance was assessed by simply inspecting the card . 100 primary care consultations were recorded, but 1 record was lost . 99 visits to home addresses were undertaken, and in 83 visits contact was made with mother and child . (( of the 83 children were regarded by their mothers as better and no longer in need of treatment . 79 of the 83 mothers interviewed were satisfied or very satisfied with the treatment provided at the clinic . At least 1 medicine was prescribed to every child at his/her initial clinic visit and in some children up to 4 . 86 children recieved an antibiotic or sulphas, or both . The majority of children seen were suffering from upper respiratory tract infections (50) or gastroenteritis, the majority of which were probably viral illnesses . The main factors for the good compliance among the population studied include: short distance from home to clinic; initial consultation took place in the mothers' own language; and the large number of intramuscular injections ordered as part of the treatment . Further education in the management of simple childhood conditions, and particularly in the use of antobiotics, needs to be given to nursing sisters conducting primary care clinics . Thorax, 1982 Jun, 37(6), 466 - 71 Morphological assessment of sucrose preservation for porcine heart valves; Drury PJ et al.; Porcine aortic valves stored in various concentrations of sucrose (50-80%) for up to 52 weeks were examined both histologically and by electron microscopy . The valves were compared with porcine aortic valves stored in a nutrient and antibiotic medium for 12 weeks . Overall preservation was better in those porcine valves stored in sucrose solution than in nutrient and antibiotic medium, the best preservation being in 50% sucrose . Despite wide separation of collagen at that concentration seen on electron microscopy (not noted histologically), tissue preservation was good after storage in sucrose solutions at concentrations up to 80%, at which clumping of collagen and distortion of fibroblasts occurred . It is suggested that sucrose solution is acceptable for the long-term preservation of biological valves. Jpn J Antibiot, 1982 Jun, 35(6), 1610 - 4 {Effects of cefoxitin on infections secondary to hematopoietic malignancies}; Sawada H et al.; Cefoxitin (CFX) was administered to 12 patients for evaluation of clinical effects of CFX against secondary infections complicated with hematopoietic malignancies, and the following results were obtained . 1 . The clinical effects were excellent in 1 and good in 8 out or 11 cases with efficacy rate of 81.8% . Out of 12 cases treated with CFX, 1 case was excluded from clinical evaluation because of prophylactic use . It is noted that all cases with pyelitis showed good response to CFX . 2 . The serum levels of CFX were determined in 1 patient with renal failure . After intravenous drip infusion of 2 g in 200 ml of glucose solution, the serum concentrations were 67.2 micrograms/ml and 7.53 micrograms/ml at 14 hours and 24 hours (after hemodialysis), respectively . 3 . No side effects attributed to CFX were observed . These results indicate that CFX is an effective and safe antibiotic for the treatment of severe infections accompanying hematopoietic malignancies. Jpn J Antibiot, 1982 Jun, 35(6), 1399 - 401 {Tissue distribution of fortimicin used in the field of obstetrics}; Komoda F et al.; A new aminoglycoside antibiotic, fortimicin, was administered intramuscularly at a dose of 200 mg, and the tissue distribution of the drug was investigated with time-course in the uterine fundus, uterine cervix, oviduct, endometrium and ovary . Patients who required total hysterectomy or uterine appendices resection due to uterine myoma, etc . were studied . The uterus levels of fortimicin were about 2 mcg/g at 2 hours after intramuscular administration in the uterine fundus and uterine cervix and reduced to trace after 8 approximately 9 hours . The genital organs levels of fortimicin were ranged from 0.71 to 4.6 mcg/g at 1 approximately 3 hours after intramuscular administration and then reduced to the levels of 0.79 mcg/g in the oviduct, of 0.25 mcg/g in the endometrium and of 0.45 mcg/g in the ovary after 5 hours. Jpn J Antibiot, 1982 Jun, 35(6), 1387 - 90 {Clinical studies of fortimicin in surgical infections}; Hosoma S et al.; A new aminoglycoside antibiotic, fortimicin, was administered intramuscularly to 3 patients (panperitonitis) . Clinical response was excellent in 2 cases and good in 1 case . The effective rate was 100% . In these patients, fortimicin was given in a dose of 600 mg, 2 or 3 times daily for 6 to 7 days . No adverse effect was observed . Therefore fortimicin was suggested to be a useful drug for the treatment of panperitonitis. Biokhimiia, 1982 Jun, 47(6), 937 - 44 {Membrane-active inhibitors of electron transport in chloroplasts}; Roshchina VV et al.; The effects of polyene antibiotic amphotericin B and the organophosphorus insecticide chlorophos (trichlorofon) on the electron transport in isolated pea chloroplasts were compared; both compounds were found to inhibit the electron transport . The concentration dependence of the inhibitory effects on the photoreactions in chloroplasts was established . Affer washing of the chloroplasts from amphotericin B admixtures the photoreduction of NADP+ was decreased by 50%, the photooxidation of cytochrome f in situ was affected comparatively little, while the photoreduction of plastocyanin in situ was decreased by 60% . The supernatant after amphotericin B washing contained plastocyanin . An addition of chlorophos to the medium caused a 70% inhibition of NADP+ photoreduction and a 40% inhibition of cytochrome f photooxidation and of plastocyanin photoreduction . It was assumed that the active site of amphotericin B lies in the plastocyanin region, that of chlorophos--at the site of NADP+ photoreduction in photosystem I . Experiments with isolated pea plastocyanin and ferredoxin and cytochrome C553 of Chlorella demonstrated that neither of the inhibitors interacts with the prosthetic groups or with he protein part of these electron carriers . Presumably the mechanism of action of amphotericin B and chlorophos on the photosynthetic electron transport consists in a destruction of chloroplast membrane structures . Using membrane-active inhibitors, the alternative pathways of electron transfer through cytochrome f and plastocyanin were established. Antibiotiki, 1982 Jun, 27(6), 434 - 7 {Experimental pharmacodynamic study of rifampicin administered by various methods}; Shapovalov VP et al.; The experimental study was performed on 80 male albino rats . The dose of rifampicin was 10 mg per 1 kg of the body weight . The highest rifampicin levels in the lung tissue were determined at all periods after intrabronchial administration of the drug . Thus, 2 hours after intrabronchial instillation of rifampicin its level in the lung tissue was 10--12 times higher than that after its enteral use . In 4 hours the antibiotic level decreased . Still, it remained 10 times higher than that after the enteral use . In 8 hours the level of rifampicin administered intrabronchially was almost the same as its maximum concentration in the lung tissue attained after the enteral use in 2 hours . By the 12th hour of the intrabronchial administration of rifampicin its concentration in the lung tissue markedly decreased . Still, it was 5--6 times higher than that after the enteral use . The rifampicin levels in the liver tissue after intrabronchial administration of the drug were at all periods much lower than those after the enteral use . The levels of rifampicin in the blood serum after its intrabronchial and enteral administration, as well as those in the liver tissue did not significantly differ. Arch Otolaryngol, 1982 Jun, 108(6), 382 - 4 Secondary syphilis of the facial nerve; Verduijn PG et al.; A 37-year-old woman had peripheral facial palsy . It took nearly two weeks to establish the syphilitic origin . This rare disease is discussed with reference to nine cases reported in the literature since 1945 . The prognosis is good with early antibiotic therapy. Lab Invest, 1982 Jun, 46(6), 545 - 53 Distribution of intramembrane particles and filipin-sterol complexes in plasma membranes of kidney . I . Corpuscle of Malpighi; Orci L et al.; A quantitative study was performed on glomerular cell types from the rat kidney freeze fractured after conventional fixation or following exposure to the sterol-specific antibiotic, filipin . The results reveal a considerable variation on the size and number of intramembrane particles, as well as in the number of filipin-sterol complexes present on plasma membranes of the different cell types present in the glomerulus . These differences in membrane structure probably reflect specialized functions of the individual plasma membranes within the glomerulus . The most striking observation, however, was the low particle content and poor filipin labeling of podocyte foot process bases (which lie against the basal lamina) compared with the rest of the podocyte plasma membrane . The presence of distinct membrane domains in podocytes may be a factor involved in maintaining their specific architecture that is critical for the normal functioning of the kidney filtration barrier. Br J Vener Dis, 1982 Jun, 58(3), 180 - 1 Treatment of uncomplicated gonorrhoea in women with talampicillin in a single oral 1.5 g dose; Mohanty KC et al.; Four hundred and sixty women with uncomplicated gonorrhea were treated with a single oral dose of 1.5 g talampicillin . The success rate among those who attended for at least one follow-up examination after treatment was 99.14% . The antibiotic was well tolerated and no side effects were reported . Talampicillin given under supervision has proved to be the most effective and safest treatment in this area . A smaller dosage of talampicillin than ampicillin is required, the drug is better tolerated by the patient, and the time of nursing staff is saved. Am Surg, 1982 Jun, 48(6), 268 - 70 Prevention of wound infection: the comparative effectiveness of topical and systemic cefazolin and povidone-iodine; Scher KS; From studies in mice, the irrigation of a contaminated surgical wound saline alone proved of little benefit . The addition of cefazolin to the irrigating solution favorably influenced the rate of infection . The most effective way to administer antibiotics topically was by the application of the antibiotic powder to the wound . Topical cefazolin administered in this way was equally as effective as systemic administration in preventing wound sepsis . Irrigation of a contamined wound with a solution of povidone-iodine was no more effective than the use of cefazolin powder but may be associated with significant toxicity. Surg Gynecol Obstet, 1982 Jun, 154(6), 870 - 4 Candida colonization of the oral cavity; Mitchell KG et al.; A quantitative study of candida colonization of the oral cavity was made in 20 normal persons, 20 patients receiving regular dialysis treatment, 21 patients who underwent operation and were in a general surgical ward and in 20 critically ill patients who had undergone operation and were in an intensive therapy unit . Candida colonization was common in the patients who had operations, and levels were highest in those receiving antibiotics . However, the administration of antibiotics was not the only factor accounting for high candida colonization, since many of the patients studied, receiving regular dialysis treatment and antibiotic therapy, had only low levels of colonization . Candida levels in the oral cavity were highest in the critically ill patients, two of whom had candida infection of the oral cavity and one patient who had systemic candidiasis . Within this group, candida colonization was not significantly different, according to the clinical outcome or the response to recall antigens . This increased candida colonization of the oral cavity may be important in the development of candida infection in these patients. Invest Ophthalmol Vis Sci, 1982 Jun, 22(6), 720 - 6 The effects of infection and probenecid on the transport of carbenicillin from the rabbit vitreous humor; Barza M et al.; We examined the effects of inflammation (S . aureus endophthalmitis) and of probenecid on the kinetics of intravitreally injected carbenicillin in rabbits . The half-life of antibiotic in the vitreous of animals with normal eyes was only 5 hr and levels in anterior ocular sites (cornea, aqueous, iris) were low . There findings are consistent with an active retinal transport pump for organic anions . Concomitant intraperitoneal administration of probenecid caused a marked prolongation of the ocular half-life of carbenicillin to 13 hr and augmentation of the levels in anterior sites, as might be anticipated from inhibition of the retinal transport pump . Inflammation produced an intermediate effect that is most readily explained by postulating two opposing consequences: partial inhibition of the transport pump and simultaneous "leakiness" of the normal retinal barrier . There findings suggest that the intraocular kinetics of antibiotics in inflamed eyes are markedly different from those in normal ones and that systemic probenecid significantly augments the intraocular levels of carbenicillin. Hum Pathol, 1982 Jun, 13(6), 596 - 7 Intracranial myospherulosis; Mills SE et al.; A 54-year-old man developed a post-traumatic brain abscess, and antibiotic ointment was instilled into the abscess cavity . The involved tissue was subsequently excised and was shown to contain the characteristic saccules and spherules of myospherulosis . The history of ointment usage further strengthens the association of petrolatum with the development of these structures . This is the first reported case of intracranial myospherulosis. Pathol Biol (Paris), 1982 Jun, 30(6), 449 - 51 {In vitro and in vivo activity of spiramycine on Chlamydia (author's transl)}; Orfila J et al.; In vitro study of spiramycine action on C . psittaci and C . trachomatis demonstrates that this antibiotic is active in a concentration similar to that found in the serum of patients who have received an injection of 4 g . However, it should be noted that even with a higher dose, few inclusions are still present . On the other hand, the action of spiramycine on mice infected with C . psittaci is highly efficient . The difference between the in vitro results and the excellent in vivo results could be explained by an important accumulation of antibiotic in the tissue. J Bacteriol, 1982 Jun, 150(3), 1234 - 43 Replication of a low-copy-number plasmid by a plasmid DNA-membrane complex extracted from minicells of Escherichia coli; Firshein W et al.; A DNA-membrane complex was extracted from minicells of an Escherichia coli mutant harboring a "miniplasmid" derivative (11.2 kilobases) of the low-copynumber plasmid RK2 (56 kilobases) . The complex contained various species of supercoiled and intermediate forms of plasmid DNA, of which approximately 20% was bound firmly to the membrane after centrifugation in a CsCl density gradient . The plasmid DNA-membrane complex synthesized new plasmid DNA without the addition of exogenous template, enzymes, or other proteins . DNA synthesis appeared to proceed semi-conservatively, was dependent on the four deoxynucleoside triphosphates, partially dependent on ribonucleoside triphosphates, and was sensitive to rifampin, an antibiotic known to inhibit initiation of replication . Novobiocin and nalidixic acid also inhibited synthesis, as did the omission of ATP, N-Ethylmaleimide, an inhibitor of DNA polymerase II and III activity, but not DNA polymerase I activity, also partially inhibited the synthetic reaction, as did chloramphenicol . The plasmid DNA synthetic product was analyzed by alkaline sucrose and dye-CsCl gradient centrifugation, as well as by agarose gel electrophoresis . In each case, the product consisted of parental and intermediate forms of plasmid DNA . Some chromosomal DNA was also synthesized by a contaminating bacterial DNA-membrane complex, but this synthesis was rifampin insensitive and could be separated from plasmid DNA synthesis. Am Rev Respir Dis, 1982 Jun, 125(6), 762 - 5 Failure of trimethoprim-sulfamethoxazole in the therapy of recurrent Pneumocystis carinii pneumonia; Mitsuyasu RT et al.; The use of trimethoprim-sulfamethoxazole in the treatment and prophylaxis of Pneumocystis cariniii is well established . Treatment failure with this regimen has been ascribed to inadequate antibiotic serum concentrations . We describe an immunosuppressed patient with recurrent Pneumocystis carinii pneumonia who failed to respond to trimethoprim-sulfamethoxazole therapy despite high antibiotic serum concentrations . Subsequently, a response to pentamidine isethionate was obtained . The reason for failure and therapeutic implications in patients with Pneumocystis carini pneumonia who have received trimethoprim-sulfamethoxazole are discussed. Am J Dis Child, 1982 Jun, 136(6), 495 - 501 Computed tomography in purulent meningitis; Bodino J et al.; Of 102 patients with bacterial meningitis admitted to the Children's Hospital of Buenos Aires, 25 were selected for computed tomographic (CT) scans on the basis of altered consciousness for more than 96 hours after admission, persistent or recurrent seizures after 72 hours of antibiotic therapy, development of focal neurologic signs, increased intracranial pressure or prolonged fever . Scan findings included hydrocephalus, cerebritis, vasculitis, subdural effusion, cerebral atrophy, abscess, and ependymitis . Serial CT scans demonstrated the progression or regression of some complications . The CT scan was very useful in indicating the need for neurosurgical procedures. Can J Microbiol, 1982 Jun, 28(6), 593 - 9 Glucose suppression of beta-glucosidase activity in a chloramphenicol-producing strain of Streptomyces venezuelae; Chatterjee S et al.; beta-Glucosidase activity was induced in Streptomyces venezuelae during growth on cellobiose, gentiobiose, salicin, methyl beta-glucoside, and p-nitrophenyl beta-D-glucopyranoside . Activity in cell extracts was separated by DEAE-cellulose chromatography into two fractions differing in substrate preference . One component showed higher activity with, and was more strongly induced by, cellobiose; the other showed greater activity and inducibility with salicin . Addition of glucose to cultures severely depressed induction of beta-glucosidase activity by cellobiose but not by salicin . Acetate and several amino acids inhibited induction by either substrate . The action of glucose was not reversed by cyclic AMP . Cultures of S . venezuelae using glucose, cellobiose, or a mixture of the two saccharides as their carbon source produced chloramphenicol during growth . In contrast with its effect on the induction of cellobiose activity, glucose did not suppress chloramphenicol production, indicating that the control mechanisms that establish carbon source preferences are not linked to those that regulate antibiotic biosynthesis in this organism. Arch Intern Med, 1982 Jun, 142(6), 1106 - 7 Rocky Mountain spotless fever: a dilemma for the clinician; Westerman EL; Failure of the characteristic rash to develop during the course of illness in Rocky Mountain spotted fever may lead to the delay or failure of diagnosis and may result in fetal encephalopathic illness with disseminated vascular injury . Four patients are described herein in whom a rash failed to develop and the diagnosis was initially incorrect . Each patient was seen at least once before hospital admission by a physician and given ineffective antibiotic therapy, resulting in fatal complications . Besides the failure of the rash to develop, the lack of any specific diagnostic test that is useful during the acute illness represents a major difficulty for the physician in making the diagnosis before the patient's death . Any adult in an endemic geographic area who is initially seen with an undifferentiated acute febrile illness in which headache and myalgias are prominent should be considered for treatment with tetracycline unless otherwise contraindicated. Pathol Biol (Paris), 1982 Jun, 30(6 Pt 2), 535 - 8 {Drug interactions with macrolids compared action of two macrolids on liver microsomal activity }; Paire M et al.; Pharmacokinetic parameters for elimination of antipyrine, regarded as a marker of the oxidative activity of liver microsomes, were studied in six health volunteers after oral administration of 1 g of the drug . Elimination half life and metabolic clearance were determined prior to (controls) and on day 2 of a treatment with troleandomycin (1500 mg/day), on days 7 and 14 of a treatment with midecamycin (1200 mg/day) and on days 7 and 14 of a treatment with phenobarbital (100 mg/day) as reference . A marked difference was evident between troleandomycin (whose inhibitor effects on the liver metabolism of certain drugs (ergot derivatives, theophylline, etc) are known, and midecamycin . This one had no inhibitor action and this finding is consistent with previous results bearing on the pharmacokinetics of theophylline during antibiotic therapy: only on the 14th day was a slight inductor effect seen, but it remained much lower than that of phenobarbital whose effects were significant on both the 7th and the 14th days. Eur J Cell Biol, 1982 Jun, 27(2), 242 - 50 A correlative study on the topographical distribution of the receptors for low density lipoprotein (LDL) conjugated to colloid gold in cultured human skin fibroblasts employing thin section, freeze-fracture, deep-etching, and surface replication techniques; Robenek H et al.; The topographical distribution of the receptors for low-density lipoprotein (LDL) conjugated to colloidal gold on cultured human skin fibroblasts was studied using a surface replication technique following critical point drying . In this correlative study, also employing thin sectioning, freeze-fracture and deep-etching techniques in conjunction with the polyene antibiotic filipin, it could be shown that LDL preferentially binds to certain microdomains of the plasma membrane, the so-called coated pits . The coated pits can be recognized after filipin treatment both on the P face and E face of the membrane, due to the fact that they are free of filipin-sterol complexes . Filipin was also of value in clearly delimiting the structure of nascent coated pits from their surroundings in surface replicas . Using filipin has the effect of increasing the contrast between the smooth surface of a coated pit and the rough surface of the remaining membrane caused by formation of filipin-sterol complexes . This study has shown that there are differences in the topographical distribution and number of gold particles from fibroblast to fibroblast and even between different areas of the same cell . The surface replication technique using goldlabelled LDL provides s suitable method for improving the interpretation of the spatial arrangement of the LDL receptors . The advantages of this technique are discussed in comparison with the methods previously employed to visualize LDL receptors. Cancer Res, 1982 Jun, 42(6), 2247 - 9 Cellular hypersensitivity to neocarzinostatin in ataxia-telangiectasia skin fibroblasts; Shiloh Y et al.; Cellular sensitivity of human skin fibroblast strains from three healthy donors, eight ataxia-telangiectasia (A-T) patients belonging to six sibships, and two A-T heterozygotes to the lethal action of the antitumor antibiotic neocarzinostatin was tested, using colony-forming ability as the criterion for survival . All the A-T strains were significantly more sensitive to killing by neocarzinostatin than were the control strains . The average D0 for the A-T strains following neocarzinostatin treatment was 14.6 ng/ml, as compared to 37.9 ng/ml for the normal strains . The two A-T heterozygous strains showed intermediate sensitivity with an average D0 of 26.9 ng/ml . Neocarzinostatin sensitivity of A-T cells could therefore serve as a convenient aid for the laboratory diagnosis of A-T . Since A-T cells are also known to be hypersensitive to ionizing radiation and bleomycin, it would appear that they are primarily hypersensitive to DNA-breaking agents. Biochim Biophys Acta, 1982 May 31, 697(2), 252 - 4 Reactivity of mitomycin C with synthetic polyribonucleotides containing guanine or guanine analogs; Weaver J et al.; The guanine residues in nucleic acids are believed to be the major covalent binding site of the antibiotic mitomycin C . To identify the specific functional group in guanine which reacts with mitomycin C, reactions were run between the antibiotic and poly(G) analogs in which guanine was blocked at the N-7 or O-6 position, or lacked the 2-amino group . Binding ratios were affected to a small extent in the two former cases, but binding was significantly decreased in the absence of the 2-amino group . These results indicate that the most likely binding site of mitomycin C in synthetic polyribonucleotides is the 2-amino group of guanine residues. Biochim Biophys Acta, 1982 May 27, 716(2), 158 - 68 Regulation of alpha-galactosidase synthesis in Saccharomyces cerevisiae and effect of cerulenin on the secretion of this enzyme; Martinez JP et al.; Saccharomyces cerevisiae -136ts MEL10 (a thermosensitive mutant whose RNA synthesis is inhibited at 37 degrees C but is normal at 23 degrees C), when grown at 23 degrees C in the presence of galactose, melibiose or L-arabinose, these cells synthesize alpha-galactosidase mRNA . In the simultaneous presence of both galactose and glucose the transcription of alpha-galactosidase mRNA is blocked . Glucose also interferes with mRNA translation, but the degree of inhibition depends on concentration and time of addition of the hexose to induced cells . It has been found that the final concentration of alpha-galactosidase produced by induced cells when transferred at the non-permissive temperature (37 degrees C) is inversely proportional to the incubation time in glucose . Cerulenin inhibits lipid formation on growing yeasts, but protein synthesis and selective permeability are not affected . The antibiotic partially inhibits secretion of alpha-galactosidase with a parallel accumulation of this enzyme in membranous structures, specially at the level of the plasma membrane . Induction of alpha-galactosidase or cerulenin addition to growing cells, results in changes in the polypeptide composition of the plasma membrane. Minerva Med, 1982 May 26, 73(22), 1563 - 6 {Epidemiologic and clinical studies of 6 cases of leptospirosis from the province of Turin}; Bosio G et al.; Six cases of leptospirosis from the outer suburbs of province of Turin are presented . Some epidemiological aspects are considered, and reference is made to the need for early diagnosis, along with prompt antibiotic management to ensure successful resolution . Mention is also made of the need for careful control of renal function, since its impairment is the most serious complication associated with leptospirosis. Eur J Biochem, 1982 May 17, 124(2), 389 - 96 Photoincorporation of tetracycline into rat-liver ribosomes and subunits; Reboud AM et al.; {3H}Tetracycline was covalently incorporated into rat liver ribosomes and isolated 40-S and 60-S subunits on irradiation at 254 nm . The antibiotic was almost exclusively incorporated into ribosomal proteins . At least some of these proteins are assumed to be involved in ribosomal function, since photoincorporated tetracycline was found to inhibit the activity of 40-S and 60-S subunits in the poly(U)-directed protein-synthesizing system as well as that of the 40-S subunit in the poly(U)-mediated {14C}Phe-tRNA binding . The results from simultaneous one-dimensional and two-dimensional gel electrophoreses showed a small distribution of label among ribosomal proteins in 60-S subunits and in 80-S ribosomes, L10 being the most radioactive protein . As non-acylated tRNA partly competed with this labeling, it is likely that tetracycline interaction with these proteins occurred at a functional site . L10 has already been found to interact with puromycin {Reboud, A . M., Dubost, S., Buisson, M . & Reboud, J . P . (1981) Biochemistry, 20, 5281-5288} . In the case of feed 40-S subunits the label distribution was wider among ribosomal proteins . No particular role has yet been found for the most labeled protein, S12, but protein S3a, which was also highly labeled, has already been reported to be involved in subunit function. Life Sci, 1982 May 17, 30(20), 1757 - 62 Cycloheximide: an adrenergic agent; Huerta-Bahena J et al.; Cycloheximide, a widely used inhibitor of protein synthesis, stimulates glycogenolysis, gluconeogenesis and ureogenesis in isolated rat hepatocytes . The effects of cycloheximide were compared to those of norepinephrine . Both agents, cycloheximide and norepinephrine, produced slight increases in the levels of cyclic AMP (30% increases) which were blocked by propranolol . Interestingly, it was found that the metabolic actions of norepinephrine and cycloheximide (stimulation of glycogenolysis, gluconeogenesis and ureogenesis) were only slightly diminished by the beta adrenergic antagonist propranolol but abolished by the selective alpha 1 adrenergic antagonist prazosin . The ability of cycloheximide to inhibit protein synthesis was not affected by either prazosin or propranolol . It is concluded that the stimulation of glycogenolysis, gluconeogenesis and ureogenesis by cycloheximide in rat hepatocytes, is an effect of the antibiotic independent of its ability to inhibit protein synthesis and that is mediated through activation of alpha 1 adrenoceptors . The adrenergic activity of cycloheximide should be considered when this drug is used as an inhibitor of protein synthesis. Biochem Pharmacol, 1982 May 15, 31(10), 1843 - 7 Further studies on the in vivo effect of cephaloridine on the stability of rat kidney lysosomes; Ngaha EO; The stabilizing effect of cephaloridine, an antibiotic, on rat kidney lysosomal membranes was tested by a single subcutaneous injection . The release of two lyososomal enzymes, acid phosphatase and muramidase, was used as an index of lysosome membrane integrity . The levels of these enzymes in the kidney extracts as well as in the isolated kidney lysosome fractions were found to be raised considerably, compared to the controls . In rats treated with cephaloridine, the supernatant fraction obtained from the kidney homogenates, after centrifugation at 15,000 gav, contained lower enzyme activities than were found in the control animals . It is suggested that cephaloridine may inhibit the release of acid phosphatase and muramidase from rat kidney lysosomes and, therefore, may exert a stabilizing effect on the lysosomal membrane system . The possible mechanism of interaction of this antibiotic with rat kidney lysosomal membranes is proposed. J Biol Chem, 1982 May 10, 257(9), 5190 - 5 Ca2+-induced lysis of platelet secretory granules; VanderMeulen J et al.; Platelet secretory granules were used for in vitro studies bearing on the mechanism of exocytosis . A morphologically homogeneous preparation of alpha-granules was obtained from porcine platelets . The granules were shown to be osmotically fragile, as determined by electron microscopy, turbidity measurements, and the release of protein upon hypotonic lysis . Lysis could also be induced in isotonic media by addition of gramicidin to granules suspended in NaCl or KCl . Increasing the osmotic strength of the medium prevented this effect . The antibiotic had no effect when added to granules in sucrose solution . Submillimolar concentrations of Ca2+ drastically reduced the turbidity of granule suspensions while releasing protein to the supernatant . Electron micrographs showed that Ca2+-treated granules lost most of their electron-dense core, indicating that lysis had occurred . Mg2+ and other divalent cations failed to induce this response . The effect occurred in NaCl or KCl but not in sucrose or sorbitol solutions . Increasing the osmotic content of the medium with sucrose suppressed the Ca2+-induced lysis . It is suggested that Ca2+ increases the ionic permeability of the granule membrane leading to solute influx followed by osmotically coupled water uptake and, therefore, swelling and lysis . During platelet activation, Ca2+-induced granule swelling could provide the driving force for membrane fusion leading to exocytosis. Science, 1982 May 7, 216(4546), 581 - 90 DNA conformation, dynamics, and interactions in solution; Patel DJ et al.; The conformation and dynamics of the d(CGCGAATTCGCG) duplex, its analogs containing mismatched base pairs and helix interruptions, and its complexes with actinomycin and Netropsin, bound separately and simultaneously, have been investigated by nuclear magnetic resonance spectroscopy in aqueous solution . Structural information has been deduced from chemical shift and nuclear Overhauser effect parameters, while the kinetics have been probed from line width and saturation recovery experiments on proton and phosphorus markers at the individual base pair level . These studies lead to an improved understanding of the role of nucleic acid sequence on the structure, flexibility, and conformational interconversions in the duplex state . The nuclear magnetic resonance measurements readily identify helix modification and antibiotic binding sites on the nucleic acid and estimate the extent to which the observed conformational and dynamic perturbations are transmitted to adjacent base pair regions. Int J Pept Protein Res, 1982 May, 19(5), 499 - 505 Crystal and molecular structure of tert.-butyloxycarbonyl-L-hydroxy-prolyl-alpha-aminoisobutyryl-alpha-aminoisobutyryl-L-phenylalaninol; Van Roey P et al.; The crystal structure of the synthetic tetrapeptide, Boc-Hyp-Aib-Aib-Phol, an analogue of the C-terminal tetrapeptide in the antibiotic antiamoebin I, was determined as part of a study of the conformation of peptaibophol antibiotics . The crystals are orthorhombic, space group P212121, with cell parameters a = 16.576 (1) A, b = 17.657 (1) A, c = 10.435 (1) A, V = 3053.9 (2) A3, Z = 4, Dc = 1.163 g.cm-3 . The three amino acids from a single turn of a 3 10-helix, stabilized by two intramolecular hydrogen bonds . The Aib residues adopt the usual conformation in the region between the 3 10- and alpha-helices . The terminal hydroxy methyl group of the phenylalaninol residue is disordered . The position of the benzyl side chain of the amino alcohol relative to the backbone corresponds to a conformation also observed in phenylalanine residues. Pharmazie, 1982 May, 37(5), 366 - 7 {Studies in mice on diminishing acute toxicity of violamycin BI by combined therapy (author's transl)}; Kirchner E et al.; In mice the effect of L-ascorbic acid (i.p., drink . wat.), DL-carnitine (i.p., drink . wat.), L-cysteine (i.p., drink . wat.), DL-methionine (i.p., drink . wat.), folic acid plus ascorbic acid (i.v.), and alpha-tocopherol (i.p.), respectively, on sublethal and lethal i.v . doses of the anthracycline antibiotic violamycin BI (VBI) was tested . The VBI induced lethality (%) of the animals was found to be unaffected by combined treatment with the drugs used . Only a delayed toxicity following alpha-tocopherol administration was observed. Med Hypotheses, 1982 May, 8(5), 465 - 72 There is a unifying view of the behaviour of gentamicin; Kar Choudhury TK; It has been observed that stress inhibits the activity of the antibiotic, gentamicin . This critical observation leads not only to an explanation of the initial physiological behaviour of the molecule but also helps accommodate the behaviour of several other ligands in their affinity for specific biomembranes . The fundamental mechanism involved is assumed to be chemisorption of the ligands to the negatively-charged lipids that facilitates a phase separation of the associated lipids . In a condensed, mixed-lipid situation, as exists in a living membrane, such a type of reaction may lead to membrane expansion and as a consequence to leakage and signal-induction . The present hypothesis develops such a view with the aid of few supplementing data and a considerable amount of supporting data selected from published literature . The hypothesis requires the rigor of modern-day instrumentation for testing. J Antibiot (Tokyo), 1982 May, 35(5), 574 - 9 Effects of N-alkylation and n-acylation on tobramycin activity; Sicsic S et al.; The activities of tobramycin derivatives acetylated and ethylated on the 6'-N,2'-N and 3-N positions were examined . The MICs of these derivatives against tobramycin sensitive strains indicated that 2'-N-ethylated and 6'-N-ethylated derivatives have a fairly good activity, and confirmed that the 3-N position is the most important one for antibiotic activity since 3-N derivatives were less active . The MICs of these derivatives against tobramycin resistant strains, and their inactivation by tobramycin modifying enzymes were examined . These results showed that 2'-N or 6'-N ethylation protects the drug against inactivation by AAC(2') or AAC(6'), respectively, and 2'-N-ethyltobramycin and 6'-N-ethyltobramycin were active against strains containing these modifying enzymes . On the other hand, 3-N ethylation protects the drug against inactivation by AAC(3) but 3-N-ethyl tobramycin does not inhibit strains containing this enzyme. J Antibiot (Tokyo), 1982 May, 35(5), 561 - 70 Chemical modification of everninomicins; Ganguly AK et al.; Novel antibiotic everninomicin D is chemically transformed into new biologically active derivatives . Reactions of a nitro group attached to a tertiary carbon center have been investigated . Synthesis and reactions of hydroxylaminoeverninomicin D, aminoeverninomicin D and their derivatives have been discussed. Antimicrob Agents Chemother, 1982 May, 21(5), 800 - 3 Rifampin blood and tissue levels in patients undergoing cardiac valve surgery; Archer GL et al.; Single 600-mg capsules of rifampin were given orally to 26 patients as prophylaxis during cardiac valve replacement . Antibiotic concentrations were measured in blood (serum or plasma) and tissue (excised cardiac valve) . The serum or plasma levels of rifampin in 18 patients who ingested this drug 2 h before they received preoperative opiates and anticholinergics intramuscularly were not significantly different from the levels in four normal volunteers who received the drug . These levels were 15.9 +/- 6.5 micrograms/ml (mean +/- standard deviation) 2 h after drug administration, 7.1 +/- 4.3 micrograms/ml 8 h after drug administration and 2 h after a mean of 1.4 h on cardiopulmonary bypass, and 1.6 +/- 1.6 micrograms/ml 24 h after drug ingestion . The valve tissue level was 3.8 +/- 2.7 micrograms/g (mean +/- standard deviation; n = 10) . This value was 65% of the simultaneous serum and plasma levels and 31% of the peak serum and plasma levels . Eight patients who were given rifampin at the same time that they received other preoperative medications had significantly lower blood levels than the 18 patients who received rifampin 2 h earlier (P less than 0.001) . No rifampin was detected in valves from seven of these patients . Decreased rifampin absorption due to simultaneous administration with opiates and anticholinergics was the probable reason for the low plasma and serum levels observed . These data suggest that, if properly dosed, rifampin administered orally gives high blood and valve tissue levels, which are affected minimally by cardiopulmonary bypass in patients undergoing cardiac valve surgery. Laryngol Rhinol Otol (Stuttg), 1982 May, 61(5), 228 - 30 {The allergic genesis of chronic-sinusitis (author's transl)}; Schlenter WW et al.; On examination of 587 patients with obstructed nasal respiration it was found that 50.2% had sinusitis . In 40.3% of these cases the origin was allergic . House dust and house dust mites and to a lesser extent moulds were the responsible agents in 82% of those patients who had perennial symptoms . The determinative diagnostic criteria in this group of patients were the intracutaneous skin test and the nasal provocation test . The RAST and the individual case history (usually reliable) were less dependable . A nasal allergy is probably the commonest cause of sinusitis . Every patient who suffers from this disease, and especially those whose sinusitis is chronic, should for this reason be examined for allergies . Anti-allergic medication should, accordingly to the diagnostic results, accompany the appropriate antibiotic therapy. Biokhimiia, 1982 May, 47(5), 713 - 23 {Probing of the linear distribution of nucleosomes in chromatin}; Kharchenko EP et al.; The binding of the antibiotic dyes to chromatin fragmented by various ways and to preparations of "complete" (MH3, 206 DNA base pairs) and "minor" MH1, 155 DNA base pairs) nucleosomes was studied . The latter were obtained from the total hydrolysate of nuclear chromatin hydrolysis by Ca-Mg-dependent endonuclease, using preparative electrophoresis in polyacrylamide gel . In liver chromatin of different vertebrate species the actinomycin D binding is decreased by 70% as compared to DNA binding, while that of ethidium bromide is reduced only by 40% . The splitting of part of internucleosomal DNA by Ca-Mg-dependent endonuclease further decreases the number of binding sites for ethidium bromide, but not for actinomycin D . MH3 bid 24 molecules of actinomycin D per 10(3) of nucleotides; their DNA contain 43.4% of GC-pairs . The GC content in MH1 is 47.7%; they bind 28 dye molecules per 10(3) of nucleotides . The data obtained are discussed in terms of possible predominant localization of nucleosomal cores in GC-pair-rich DNA sites. Biofizika, 1982 May-Jun, 27(3), 391 - 8 {Thermodynamic parameters characterizing interaction between ligand molecules adsorbed on a polymer}; Nechipurenko IuD; Procedure was elaborated for recognizing potentials of paired interactions between ligand molecules adsorbed on the polymer . A method is proposed for describing such interactions by means of the potentials of simplest shapes, rectangular and trapezoidal ones . It is shown that when the interactions cover the distances much larger than the mean ones between the adsorbed molecules, the adsorption is described by the expression specific for noncooperative binding of the ligands . On this basis the method for analysing the experimental isotherms of adsorption is developed . It permits estimation of the interaction energy between the ligand adsorbed molecules and specific distance to which these interactions are distributed . This method is applied for analysing experimental isotherms of adsorption of antibiotic distamycin A on poly (dG) . poly (dC). Br J Nutr, 1982 May, 47(3), 565 - 76 Properties of a novel series of inhibitors of rumen methanogenesis; in vitro and in vivo experiments including growth trials on 2,4-bis (trichloromethyl)-benzo {1, 3}dioxin-6-carboxylic acid; Davies A et al.; 1 . A procedure for measuring methane production by rumen contents incubated anaerobically in vitro is described . Assessments of methane production in vivo, in both sheep and cattle, were made by withdrawal of rumen contents and measuring their capacity to produce methane in vitro . 2 . Many members of a series of 6-substituted 2,4-bis (trichloromethyl)-benzo{1,3}dioxins were potent inhibitors of methanogenesis by rumen contents in vitro . The most potent compound inhibited methane production by 70% or more at a concentration of 1 microgram/ml (approximately 2.5 mumol/l) . 3 . Two compounds, namely the 6-carboxylic acid (ICI 13409) and the 6-carboxamide (ICI 43586), caused a large inhibition of methanogenesis sustained for many hours, following a single intrarumen injection in sheep or cattle . Inhibition was maintained for long periods by single daily dosing directly into the rumen or by dietary administration . 4 . In a 28-week growth trial in beef cattle inclusion of ICI 13409 in the concentrate element of the diet, at a level of 6 mg/kg body-weight, improved live-weight gain by 8.0% (P less than 0.05) with respect to untreated animals whilst reducing food intake by 5.0% (P less than 0.05) . Smaller and not statistically-significant effects were seen with this compound at 3 mg/kg body-weight and with the antibiotic monensin (Romensin; Elanco PLC) . All treatments significantly improved the retention of dietary energy into the carcass, offal and intestinal tracts of the trial animals and significantly reduced the quantity of methane eructed into expired gases. Br J Audiol, 1982 May, 16(2), 147 - 50 Bobbing oscillopsia from gentamicin toxicity; Ramsden RT et al.; A series of 15 patients had been studied, all of whom suffered severe labyrinthine damage from gentamicin . All subjects were patients in a renal unit and had been in renal failure . The antibiotic was administered, either intramuscularly, intravenously or into the dialysate . In most of the patients there was a history of previous or simultaneous administration of another ototoxic agent, either another aminoglycoside, or a loop diuretic . None of the patients developed severe vertigo . They consistently complained, when they eventually were able to get out of bed, a vertical bouncing of their surroundings, when they walked, coinciding with each step . This sensation is made worse if the patient runs, or drives on a bumpy road, and stops as soon as the patient stands still . Caloric tests revealed non-functioning labyrinths on both sides . Gradual improvement in the symptom occurred over a period of months . No cochleotoxic effect was observed . The probable mechanism of this phenomenon is discussed. J Allergy Clin Immunol, 1982 May, 69(5), 455 - 60 Steroid-specific and anticonvulsant interaction aspects of troleandomycin-steroid therapy; Szefler SJ et al.; Troleandomycin (TAO) is a macrolide antibiotic that has an apparent "steroid-sparing" effect when used in the treatment of severe steroid-dependent asthmatic patients . Recent observations demonstrated the effect of TAO on inhibiting methylprednisolone elimination, possibly contributing to its beneficial effects . Prednisolone and methylprednisolone disposition were studied before and 1 wk after initiation of TAO therapy in three patients . Methylprednisolone elimination was characteristically impaired in the presence of TAO therapy; however, there was no apparent effect on prednisolone elimination . Methylprednisolone elimination was also evaluated before and after initiation of TAO therapy in three patients receiving concomitant anticonvulsant therapy with phenobarbital-1, phenytoin-2 . Methylprednisolone clearance before TAO was at least 4 times faster than normal and was probably related to enzyme induction by the anticonvulsant medication . Methylprednisolone clearance was subsequently reduced by approximately 70% in the presence of TAO therapy . The effect of TAO on corticosteroid disposition is steroid-specific and TAO can diminish the effect of certain drugs on the induction of corticosteroid metabolism. Antibiotiki, 1982 May, 27(5), 359 - 64 {Experimental study of the endolymphatic use of gentamycin and klaforan (cefotaxime)}; Shcherbakova EG et al.; Distribution of gentamycin and klaforan in the lymphatic system, blood and cerebrospinal fluid, as well as their effect on lymph node morphology was studied experimentally on 46 dogs . The antibiotics were administered endolymphatically in doses of 1 and 30 mg/kg respectively . The highest levels of gentamycin (200-250 micrograms/ml) and klaforan (up to 1600 micrograms/ml) were detected in the central lymph . The therapeutic levels of the antibiotics in the central persisted for 24 and 72 hours respectively . The antibiotics accumulated mainly in the regional (inguinal and pelvic) lymph nodes, where their high levels were determined for 72 hours . The levels of the antibiotics in the distant (cervical and tracheobronchial) lymph nodes were lower and did not exceed the therapeutic ones . They persisted for 6 and 24 hours respectively . No unfavourable effect of the antibiotics on the structure and cell composition of the lymph nodes was noted . After endolymphatic administration in the above doses the antibiotic levels in the blood serum were close to those observed after administration by the routine routes . After endolymphatic administration in the above doses the antibiotics penetrated into the cerebrospinal fluid. J Virol, 1982 May, 42(2), 678 - 90 Herpesvirus glycoprotein synthesis and insertion into plasma membranes; Peake ML et al.; In the presence of the antibiotic tunicamycin (TM), glycosylation of herpes simplex virus glycoproteins is inhibited and non-glycosylated polypeptides analogous to the glycoproteins are synthesized (Pizer et al., J . Virol . 34:142-153, 1980) . The synthesis of viral proteins and DNA occurs in TM-treated cells . By electron microscopy, nucleocapsids can be observed both in the nucleus and the cytoplasm of TM-treated cells; a small number of enveloped virions were observed on the cell surface . Analyses of the proteins in partially purified virus readily detects viral glycoproteins in the control cells, but neither glycoproteins nor nonglycosylated polypeptide analogs were observed in the virus prepared from TM-treated cells . By labeling the surface of infected cells with 125I, viral glycoproteins were detected as soon as 90 min after infection even when protein synthesis was inhibited with cycloheximide and glycosylation was blocked with TM . Labeling the proteins synthesized in infected cells with {35S}methionine showed that the surface glycoproteins detected in the cycloheximide- and TM-treated cells were not synthesized de novo after infection, but were placed on the cell surface by the infecting virus . Studies with metabolic inhibitors and a temperature-sensitive mutant blocked early in the infectious cycle showed that glycoproteins gA/gB and gD were synthesized soon after infection, but that the synthesis of gC was delayed . Under conditions of infection, in which gC and its precursor pgC are not produced, we have been able to observe the relationships between the glycosylated polypeptides that correspond to pgA/pgB and the nonglycosylated analog made in the presence of TM. Med Clin North Am, 1982 May, 66(3), 675 - 87 Current management of fungal enteritis; Chretien JH et al.; Fungal infections of the gastrointestinal tract have risen to higher levels of prevalence in the past decade . Major factors accounting for this increase are social changes, such as the increased ease and frequency of travel, which exposes the individual to environmental conditions that may result in fungal infection; increasing use of antibiotic and hormonal medications by otherwise healthy persons; and improved therapy for other diseases, such as polychemotherapy of cancer with its immunosuppressive effects . Both noninvasive and invasive fungal disease of the intestinal tract in otherwise healthy individuals can be successfully treated . The invasive fungal infections in patients with severe prior underlying disease are often first diagnosed postmortem, but improvement in serologic techniques now offers a possibility of earlier diagnosis and therapeutic intervention. Mol Cell Biol, 1982 May, 2(5), 508 - 16 Dependence of nucleus-directed rRNA synthesis upon mitochondrial protein synthesis in Tetrahymena; Ruben L et al.; The antibiotic chloramphenicol selectively inhibited mitochondrial protein synthesis in the ciliate protozoan Tetrahymena pyriformis GL . Secondary to the inhibition of mitochondrial protein synthesis was an inhibition of nuclear RNA synthesis at a time before inhibition of cellular protein and DNA synthesis . Of the stable non-polyadenylated RNA species in Tetrahymena, the addition of chloramphenicol resulted specifically in the inhibition of synthesis of 28S + 17S and 5S rRNA transcripts . By contrast, syntheses of 4S tRNA and 21S mitochondrial rRNA were not as extensively inhibited . The addition of 60 microM hemin before the addition of chloramphenicol partially protected against the inhibition of RNA synthesis . These data indicate that continued synthesis of nucleus-directed rRNA is linked to the synthesis of mitochondrial proteins in Tetrahymena. J Antibiot (Tokyo), 1982 May, 35(5), 571 - 3 Chemical and biological properties of formyl gramicidins S; Srinivasa BR; The mono- and diformyl gramicidins S have been prepared . Monoformyl gramicidin S retains about 50% of the expected biological activity and the diformyl derivative is inactive . It is therefore, conceivable that both the amino groups equally contribute to the biological activity of the antibiotic . However, monoformyl gramicidin S has been found to form aggregate and this aggregate is more stable under acidic conditions rather than in neutral or alkaline solutions . Denaturing agent urea has been found useful in dissociating the aggregate . The aggregating ability of formyl peptides is at least be due to their formyl groups. Biofizika, 1982 May-Jun, 27(3), 445 - 9 {Gramicidin A-induced membrane conductance of isolated muscle fiber}; Shvinka NE et al.; The conductance of single fibres from m . ileofibularis of Rana esculenta was studied in isotonic K2SO4 solution under constant--current conditions using the double sucrose gap method . The antibiotic gramicidin A effects a drastic increase of membrane conductance . Variation of the gramicidin-induced conductance with gramicidin concentration in the bathing solution (10(-8)-5,5 . 10(-7) M) was investigated . Gramicidin-induced conductance was proportional to the square of gramicidin concentration in the solution, as expected in a channel made of gramicidin dimer. J Bacteriol, 1982 May, 150(2), 598 - 603 Control of the actinomycin biosynthetic pathway in and actinomycin resistance of Streptomyces spp; Ochi K; Using actinomycin-producing and nonproducing strains of Streptomyces antibioticus, I studied several steps in the biosynthetic pathway of this antibiotic . Actinomycin-nonproducing strains derived after acriflavine or novobiocin treatment showed activity of kynurenine formamidase and phenoxazinone synthase as high as that of the parental strain, but these nonproducing strains failed to convert 4-methyl-3-hydroxy-anthranilic acid to actinomycin . In addition, accumulation of 4-methyl-3-hydroxyanthranilic acid (in the presence of D-valine) was not detected in the nonproducing isolates . Actinomycin-nonproducing strains derived after acriflavine treatment of Streptomyces parvulus showed a drastic decrease of resistance to the antibiotic . However these strains regained resistance after preincubation with a small amount of actinomycin D. Wien Klin Wochenschr, 1982 Apr 30, 94(9), 231 - 5 {Bacterial nosocomial infections in urology: defective wound healing}; Schmidbauer CP et al.; The highest incidence of defective wound healing in all surgical disciplines is observed after urological operations . Wound infections occur in more than 8% of all urological patients . Defective wound healing appears in about 17% of unselected nephrectomy cases, rising to 50% when pyonephrosis is present . Simple adenomectomy is associated with wound infection rates of between 8 and 12% in preoperatively uninfected patients and up to 50% in patients with preoperative bacteriuria . Numerous factors may influence wound healing, e.g . age, obesity, cachexia, chronic infectious and non-infectious diseases, anaemia, thrombopathy, faulty asepsis and antisepsis, preoperative showering and shaving, skin preparation, hand degerming, skin draping, duration of hospitalization, traumatic operative technique, suture material, diathermy, timing and length of operation, duration of hospitalization, and antibiotic regimen . Strict attention has to be paid to these factors if the incidence of postoperative wound infection is to be kept within reasonable limits. Br Med J (Clin Res Ed), 1982 Apr 10, 284(6322), 1078 - 81 Trial of three-day and ten-day courses of amoxycillin in otitis media; Chaput de Saintonge DM et al.; A randomised double-blind controlled trial compared three-day and 10-day courses of amoxycillin (25 mg/kg daily) in children with otitis media . Seventeen doctors from five centres admitted 84 children between the ages of 2 and 10 years . Symptoms and signs were measured on admission to the trial, on day 3, and on day 15 . Mother's observations were recorded daily for 10 days . Audiograms were performed at four and 12 weeks after the end of the trial . The treatment groups showed little difference in the speed of resolution of symptoms and signs, the numbers of primary treatment failures, or the frequency of recurrent ear infections . There were no complications in either group . Most children with otitis media can probably be successfully and safely treated with no more than a three-day course of amoxycillin providing their progress is reviewed about the fifth or sixth day after treatment started . This policy could save over 1 million pounds annually in antibiotic costs. Gan To Kagaku Ryoho, 1982 Apr, 9(4), 575 - 81 {In vitro tumor sensitivity tests to chemotherapeutic agents by the suppression of dehydrogenase activity}; Ichihashi H et al.; A test system using dehydrogenase activity for predicting the response to chemotherapeutic agents against cancer cells was introduced . Agar plate assay, INK which test, and SDI test commonly employed in the clinical study were also reviewed . Agar plate assay resembles antibiotic disc sensitivity test . The cancer uniformly suspended in the agar medium was exposed to drugs on paper discs for few hours . After removal of the disc, methylene blue or 2, 6-dichlorophenol indophenol was applied as a dehydrogenase indicator . INK test was introduced by Nishioka et al . in 1957 . Several fragments of fresh cancer tissue were incubated with chemotherapeutic agents in roller test tubes . Twenty-four hours later, 2, 6-dichlorophenol indophenol was applied as a dehydrogenase indicator . To develop a simple, rapid, and comparable test, SDI test was introduced by us in 1964 . A fresh cancer tissue was minced and made into the cell suspension . After cancer cells were exposed to chemotherapeutic agents, the activities of succinic dehydrogenase of the treated cells were measured by the reduction of 2, 3, 5-triphenyl tetrazolium chloride . Some points to be improved were investigated and discussed. Gan To Kagaku Ryoho, 1982 Apr, 9(4), 570 - 4 {History and significance of sensitivity test of anticancer drugs}; Taguchi T; Many anticancer drugs are now available for clinical use . Unfortunately, most are extremely toxic to normal tissue . Use of one or more toxic drugs inactive against the given patient's own cancer may not only deny the patients the benefit of active therapy but may actually make the patient's cancer grow faster . The need for adjuvant chemotherapy can scarcely be doubted . However, distant metastases may be present at the time of primary surgery in many cases . Some form of generalized therapy like drug therapy or immunotherapy must therefore be used to supplement our local form of treatment such as surgery and radiation therapy for cancer . Already the dangers of cancer chemotherapy are reported as adverse effect, not only in the case of advanced cancer patients, but, that of post operative adjuvant chemotherapy . Therefore, predictive assays analogous to antibiotic sensitivity tests are needed to rule out inactive drugs and select active drugs with least toxicity . The treatment of patients with cancer according to the result of tests of sensitivity of cancer cells to anticancer drugs has been introduced many years ago . The examination of the sensitivity is carried out on explanted tumor cells by two different methodical approaches-observation of the cytotoxic effect of the preparation tested to the growth of the tissue culture of the tumor examined, and a short-term examination with the indication of the effect of anticancer drugs according to the decreased utilization or incorporation of the precussors of the synthesis of proteins, RNA and DNA labeled with radioisotopes, or according to the release of enzymes from tumor cells damaged by an efficient anticancer drug . However, clinicians know that there are many disagreements between the sensitivity test and clinical results . Each sensitivity test has its limitation and problems for resolution . Research toward the goal of the sensitivity test is to divise more appropriate method which is simple prompt and precise for drug selection. Avian Dis, 1982 Apr-Jun, 26(2), 450 - 7 Early detection of tracheal damage in chickens by scanning electron microscopy; Hod I et al.; Fifteen-day-old chickens were inoculated with effective doses of cultured Mycoplasma gallisepticum and treated with the antibiotic tiamulin or tylosin . Scanning electron microscopy was used to detect early and late damages in the tracheal mucosa of the affected birds . Edematous changes of various degrees were demonstrated as early as day 4 postinoculation . Catarrhal changes were observed at day 10 postinoculation, and obstruction of the tracheal lumen by mucofibrinous plugs was observed at day 10 or later postinoculation . Scanning electron microscopy was useful in early detection of inflammatory changes in the trachea of apparently healthy chicks. Avian Dis, 1982 Apr-Jun, 26(2), 422 - 5 Reduced mortality among young endangered masked bobwhite quail fed oxytetracycline-supplemented diets; Serafin JA; Two experiments were conducted to examine the effect of oxytetracycline-supplemented diets on mortality of young endangered masked bobwhite quail (Colinus virginianus ridgwayi) . Inclusion of oxytetracycline at 200 g per ton in the feed for 6 weeks resulted in a marked, significant reduction in mortality of young masked bobwhite quail raised in captivity . Including the antibiotic in feed during the first week of life reduced mortality as effectively as feeding it for a longer period. Jpn J Antibiot, 1982 Apr, 35(4), 960 - 6 {Absorption, distribution, metabolism and excretion of netilmicin in rats (II) . Accumulation study of netilmicin after repeated administration}; Ohashi H et al.; Repeated administration of netilmicin (NTL), a new aminoglycoside antibiotic, to rats at daily intramuscular dose of 10 or 20 mg/kg for 22 days did not affect the plasma level and the plasma half-life of the drug . The concentrations of NTL in the kidney increased markedly after repeated administration, and reached peak level after 8 and 15 doses for 10 and 20 mg/kg, respectively . Cumulative effect of NTL after repeated dose was also observed in the liver, spleen and lung, although the peak concentrations of NTL in these organs were below 1/50 of that in the kidney . Blood and tissue levels of NTL in rats were determined after a single intramuscular administration of 14C-NTL at a dose of 20 mg/kg following 21 repeated intramuscular administrations of NTL at daily dose of 20 mg/kg . The repeated dose of NTL had no effect on the blood level-time curve of radioactivity . The concentration of NTL in the kidney determined by radioassay was about 1/3 of that determined by bioassay, whereas the half-lives in the tissue levels determined by these two assays were nearly identical with each other . The half-life in the lung determined by bioassay was almost identical to that determined by radioassay, whereas the former was rather shorter than the latter in the liver and spleen. Antibiotiki, 1982 Apr, 27(4), 287 - 92 {Elaboration of the procedures for the pharmacokinetic interpretation of aminoglycoside nephrotoxicity: the experimental evaluation of the safety of repeated gentamycin administration}; Firsov AA et al.; Nephrotoxicity and pharmacokinetics of gentamicin were studied on rats treated with the antibiotic for 30 days in doses of 6.25, 12.5 and 25 mg/kg administered daily . The pharmacokinetics of gentamicin and the time course of changes in the urea nitrogen levels of the blood serum were studied after the 1st, 5th, 8th and 30th injection . The analysis of the respective curves was used for calculation of the average integral values of the concentrations of the antibiotic (C) and urea nitrogen (E) . After that the average integral values of these parameters ((CAVG and EAVG respectively) within the whole treatment couse with the use of every dose were calculated in the same way by using the curves of the dynamics of C and E changing . Comparison of the diagrams of E dependence on C for gentamicin and sisomycin showed that nephrotoxicity of sisomycin was 1.48 times higher than that of gentamicin. Arch Intern Med, 1982 Apr, 142(4), 807 - 8 Severe vertebral osteomyelitis in patients with spinal cord injury; Malik GM et al.; Four patients with spinal cord injury (SCI) experienced severe and unusual clinical manifestations of vertebral osteomyelitis . The main feature of the illness was the development of extensive disease below the level of the SCI . Large paravertebral abscesses pointing to the skin developed in three patients . The fourth patient was seen initially with a persistent draining sinus on a previous nephrectomy incision site before the condition was diagnosed . All four patients underwent surgical debridement of infected bone together with antibiotic therapy . Vertebral osteomyelitis should be considered in patients with SCI and sepsis of uncertain origin. Circ Res, 1982 Apr, 50(4), 547 - 53 Interaction of adriamycin in vitro with cardiac myofibrillar proteins; Lewis W et al.; Binding of the anthracycline antibiotic doxorubicin {Adriamycin (ADR)} to selected cardiac muscle contractile proteins was determined in purified canine heart actin and alpha-actinin . Adriamycin binding to these proteins in solution was measured by equilibrium dialysis and gel filtration with {14C}-labeled ADR . Adriamycin did not bind when its primary amino group was blocked . Adriamycin binding did not affect actin polymerization as detected by viscometry . Viewed under the electron microscope, however, ADR promoted formation of distinct actin filaments in the presence of microM amounts of ATP without K+ and MG++ . Adriamycin-induced actin microfilaments were thicker (120 A) than those of F-actin controls (70 A) and stimulated myosin-ATPase to higher levels than the F-actin controls . It appears that ADR has a direct effect on the biophysical and biochemical properties of heart myofibril proteins in vitro. Biokhimiia, 1982 Apr, 47(4), 671 - 7 {Interaction of alkaline phosphatase and acid phospholipids in E . coli cells and artificial membranes}; Nesmeianova MA et al.; The synthesis of alkaline phosphatase, an enzyme secreted by E . coli, is decreased in the cells pretreated with the lipotropic antibiotic polymixin prior to derepression . The decrease of the enzyme synthesis in the cell is correlated with the changes in the intracellular and intramembrane ratios of acid phospholipids, presumably at the level of the cytoplasmic membrane . The interaction between alkaline phosphatase and artificial lipid membranes has been shown to be a function of pH and ionic strength and is increased in the liposomes rich in acid phospholipids and decreased in the polymixin-treated liposomes. Antimicrob Agents Chemother, 1982 Apr, 21(4), 608 - 12 Fosfomycin resistance plasmids do not affect fosfomycin transport into Escherichia coli; Leon J et al.; Escherichia coli cells carrying fosfomycin resistance plasmids were able to take up fosfomycin from the medium to the same extent as plasmid-free bacteria . The antibiotic entered the plasmid-harboring cells by means of the glpT and uhp transport systems, as is the case with susceptible bacteria . Active fosfomycin could be detected in soluble extracts of cells which had previously been incubated in the presence of the antibiotic . Furthermore, fosfomycin resistance plasmids did not confer on E . coli cells resistance to the novel antibiotic FR-31564, which is incorporated by the same transport systems as fosfomycin . We conclude that, in contrast to chromosomal resistance mutants, altered transport does not play a role in the plasmid-encoded fosfomycin resistance mechanism. Clin Chem, 1982 Apr, 28(4 Pt 1), 659 - 61 Quantitation of haptens by homogeneous immunoprecipitation . 1 . Automated analysis of gentamicin in serum; Wu JW et al.; A new homogeneous immunoprecipitation inhibition assay has been developed to quantitate concentrations of hapten in human serum or plasma without the use of radioactive isotopes, enzymes, fluorescent markers, or laser nephelometers . This immunoprecipitation is based on spectrophotometric measurement of the inhibition by free hapten of the precipitating reaction between antihapten antibody and polyhaptenic antigen . The immunoprecipitation analysis of the antibiotic gentamicin in human serum is reported here . A serum test sample is mixed with gentamicin-human serum albumin polyhaptenic conjugate and rabbit antiserum to gentamicin on a centrifugal analyzer, and the subsequent reaction monitored for 3 min . No sample dilution or pretreatment is required . The within-run and between-run coefficients of variation are well below 10% . The results on patients' test samples correlate well with those obtained by commercially available radioimmunoassay and enzyme immunoassay kits. Drug Intell Clin Pharm, 1982 Apr, 16(4), 295 - 300 Chloramphenicol: new perspectives on an old drug; Powell DA et al.; Chloramphenicol is an old antibiotic being used with increasing frequency in serious childhood infections largely due to the emergence of ampicillin-resistant Hemophilus influenzae type b . Because of this renewed popularity and the recent availability of accurate analytical techniques for measurement of chloramphenicol, there have been many recent articles examining the pharmacokinetics of chloramphenicol and its two major prodrug esters, chloramphenicol succinate and chloramphenicol palmitate . New data from these studies include the incomplete bioavailability of chloramphenicol succinate, the possible superior bioavailability of chloramphenicol palmitate vs . chloramphenicol succinate, and the wide interpatient variability in chloramphenicol clearance . These observations, coupled with the known serious hematologic toxicity (reversible bone marrow suppression or irreversible aplastic anemia) and metabolic toxicity (gray baby syndrome) associated with chloramphenicol use, require that initial antibiotic doses be selected by age and be carefully individualized by measurement of peak serum chloramphenicol concentrations. Proc Natl Acad Sci U S A, 1982 Apr, 79(8), 2598 - 602 Distribution of cytochemically detectable cholesterol in the electric organ of Torpedo marmorata; Perrelet A et al.; A cytochemical probe for cholesterol, the polyene antibiotic filipin, was applied to aldehyde-fixed samples of the electric organ of Torpedo marmorata to identify filipin-binding sites in the various membrane components of the organ and, hence, the probable cholesterol content at these levels . In both thin-sectioned and freeze-fractured samples, filipin-cholesterol complexes appeared numerous and homogeneously distributed on the Schwann cell plasma membrane . On the presynaptic membrane, filipin-cholesterol complexes occurred in patches alternating with unlabeled membrane segments . The postsynaptic, acetylcholine receptor-rich plasma membrane of the electroplax showed no or few filipin-cholesterol complexes in the flat region and upper part of the invaginations (both areas characterized by a lattice of small intramembrane particles); however, the membrane of the bottom part of the postsynaptic invaginations contained several complexes . The ventral, noninnervated plasma membrane of the electroplax showed a moderate, homogeneous filipin labeling . These data suggest that the distribution of cholesterol among membranes of the electroplax is not homogeneous and that the acetylcholine receptor-rich region of the postsynaptic membrane (as characterized by the lattice of small intramembrane particles) may contain little cholesterol. Int J Oral Surg, 1982 Apr, 11(2), 106 - 9 Concentration of phenoximethylpenicillin, clindamycin and tinidazole in dental cysts; Bystedt H et al.; In the treatment of bacterial infections, adequate antibiotic concentrations must be realised at the site of infection . Levels of 3 antibiotics--phenoximethylpenicillin, clindamycin and tinidazole - were measured in serum and fluid of periapical odontogenic cysts in 30 patients undergoing enucleation of periapical cysts . After a single dose of 500 mg tinidazole, the concentration of tinidazole in the cystic fluid was 4.3 micrograms/ml, which was about 1/3 of the concentration in the serum . No measurable levels were achieved in the cystic fluid with phenoximethylpenicillin or clindamycin. Antimicrob Agents Chemother, 1982 Apr, 21(4), 595 - 600 Modulation of bleomycin cytotoxicity; Moore CW; Lethal effects of a 75-microgram/ml concentration (approximately 5 X 10-5 M) of bleomycin on stationary-phase haploid or diploid cells of the eucaryote Saccharomyces cerevisiae were negated in the presence of 0.05 M phosphate buffer (pH 7) . High cell densities (2 X 10(8) cells per ml) further inhibited killing . Multiphasic survival curves resulting after treatments in deionized water (pH 6.7) suggested the presence of cells with differing susceptibilities either at the start of treatment periods or as a result of resistance which developed during exposure to antibiotic . To identify a delayed effect, prolonged lethal consequences of the action of bleomycin were investigated under liquid-holding conditions . Survival of untreated early-stationary-phase yeast cells was not significantly affected by incubation without antibiotic for 6 or 36 h in non-nutrient buffer or water . However, increased killing resulted after bleomycin-treated cells were incubated in the absence of bleomycin or buffer . Moreover, cells which had never been exposed to the antibiotic lost considerable colony-forming ability as a result of incubation with bleomycin-treated cells, indicating the efflux of bleomycin or a reaction product . The findings have implications for both experimental cell studies and cancer therapy, as well as for the chemical mechanisms by which a metal bleomycin complex could cause killing. Aktuelle Traumatol, 1982 Apr, 12(2), 43 - 7 {External fixator in the prevention and treatment of infections (author's transl)}; Weller S; Although postoperative infection constitutes a serious complication after osteosyntheses of closed fractures and in the course of open fractures, application of the known principles permits the adaption of an optimistic attitude towards treatment . Stability of osteosynthesis preferably with external fixation, open-wound treatment with regular control of the wound, in special cases suction-irrigation drainage, local application of PMMA beat chains and short-term, high-dosed systemic antibiotic therapy after antibiogram are amongst the most important points to be taken into consideration. J Biol Chem, 1982 Mar 25, 257(6), 3105 - 9 Relationship of the structure and biological activity of the natural homologues of tunicamycin; Duksin D et al.; The antibiotic tunicamycin was separated into 16 different components using reversed-phase high performance liquid chromatography . The effect of the eight major tunicamycin homologues on protein glycosylation and protein biosynthesis was examined . All homologues tested inhibited lipid-mediated protein glycosylation in chick or mouse fibroblasts . These homologues also inhibited the transfer of N-acetylglucosamine-1-phosphate from UDP-N-acetylglucosamine to dolichyl phosphate in chick liver microsome preparations, whereas the transfer of mannose from GDP-mannose to the lipid acceptor was hardly affected . The inhibition of protein glycosylation in fibroblasts or in microsomal preparations was concentration-dependent and maximum inhibition occurred at different concentrations for different homologues . The eight homologues differed in their ability to cause inhibition of protein synthesis. Biochem Pharmacol, 1982 Mar 15, 31(6), 1123 - 9 Inhibition of phosphoenolpyruvate carboxykinase by streptonigrin; Merryfield ML et al.; Streptonigrin, an antibiotic with antineoplastic activity, inhibited rat liver phosphoenolpyruvate carboxykinase with an I50 of 0.3 microM when excess FeCl2 was present . No inhibition occurred in the absence of added metal ion . Inhibition was partial and noncompetitive versus ITP and oxalacetic acid . The enzyme was more susceptible to inhibition by streptonigrin in the absence of substrates . Fe2+ supported inhibition by streptonigrin to a greater extent than did Fe3+, while Mn2+ activated the enzyme in the presence of streptonigrin . For maximum inhibition, at least a 3-fold molar excess of iron over streptonigrin was required . The methyl ester of streptonigrin was also an inhibitor (I50 = 4 microM) while the fragment containing the C and D rings was not, indicating that inhibition did not depend solely on the presence of the picolinic acid moiety . When oxalacetate synthesis was measured, streptonigrin plus iron had no more effect on enzymatic activity than iron alone, and Mn2+ was capable of stimulating the streptonigrin-Fe2+ inhibited enzyme. Nucleic Acids Res, 1982 Mar 11, 10(5), 1721 - 32 Differential stabilization by netropsin of inducible B-like conformations in deoxyribo-, ribo- and 2'-deoxy-2'-fluororibo-adenosine containing duplexes of (dA)n . (dT)n and (dA)n . (dU)na; Zimmer C et al.; Six polynucleotide duplexes containing polydeoxyadenylic acid, polyadenylic acid or poly-2'-deoxy-2'-fluoro-adenylic acid in one strand, and polydeoxyuridylic acid or polydeoxythymidylic acid in the other strand have been studied by circular dichroism, ionic strength dependence of melting temperatures and binding of the DNA specific antibiotic netropsin . Circular dichroism spectra of (dA)n . (dT)n and (dA)n . (dU)n indicated the presence of the B-form of DNA, while those of (dAfl)n . (dT)n and (rA)n . (dT)n (and the corresponding (dU)n hybrids) indicated the presence of the A-form . (dAfl)n . (dT)n and (dAfl)n . (dU)n bound netropsin only slightly less than the (dA)n containing duplexes, while replacement by (rA)n decreased netropsin binding to a large degree . Since netropsin requires B-DNA for binding, it is concluded that the A to B transition is facilitated in the case of fluorine substitution in the sugar moiety, while the 2'-OH group greatly limits this conformational change. Boll Ist Sieroter Milan, 1982 Mar, 61(1), 64 - 70 {Serum and bronchial concentrations of amoxicillin administered with a bronchial fluidizer}; Concia E et al.; The authors compared the serum and bronchial concentration of amoxycillin administered alone and in association with carboxymethylcysteine . The determinations were carried out in 10 patients affected with exacerbated acute and chronic bronchopneumopathies, treated first with amoxycillin alone (15 g/day in 3 administrations) and then with amoxycillin at the same dosage and carboxymethylcysteine (450 mg/day in 3 administrations) . The bronchial secretions were collected during bronchoscopy performed 2 hours after the last administration of antibiotic . The bronchial secretion values of amoxycillin administered alone varied from 0.92 mcg/ml to 1.88 mcg/ml with a mean value of 1.44 mcg/ml . The percentage ratio between levels in bronchial secretion and levels in the serum varied from 12.7 to 36.1 with a mean value of 23.2 . The administration of the amoxycillin-fluidizing agent association determined a statistically significant increase of the antibiotic levels in the bronchial secretions, varying from 1.26 mcg/ml to 6.39 mcg/ml, with a percentage ratio from 19.6 to 103.0. Boll Ist Sieroter Milan, 1982 Mar, 61(1), 58 - 63 {Effect of S-carboxymethylcysteine on blood levels of amoxycillin and its diffusion through lung parenchyma and pleural exudate in the rat}; Broccali G et al.; The fixed combination (10 : 3) of amoxycillin and S-carboxymethylcysteine, which is i