Antibiotics

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 indicated in the therapy of the respiratory tract infections, was given to rats by oral route to determine the blood levels and the concentrations in the pulmonary parenchyma and pleural exudate . In comparison with the antibiotic alone the combination determined higher levels of amoxycillin in the blood (0.5, 1.2 hours after administration) in the homogenized lung tissue (2 hours after administration) and in pleural inflammatory exudate (0.5, 1, 2 hours after administration) caused by intrapleural injection of carrageenan . The enhanced distribution of the antibiotic in the target tissues further supports the clinical usefulness of this combination.

Bull Soc Pathol Exot Filiales, 1982 Mar-Apr, 75(2), 131 - 5
{Treatment of Borrelia infected ticks (author's transl)}; Karimi Y; The Ornithodorus tholozani, carrier and main reservoir of Borrelia persica, causing agent of the regional recurrent fever in Iran, gets rid of the infection by stuffing in blood containing a cycline type antibiotic, in an adequate concentration . The treatment efficiency is 100%, confirmed on 60 infected ticks who showed to be free from Borrelia after a treatment meal, so that the crushing of their whole body, inoculated to the guinea-pig, the most sensitive animal to Borrelia persica, remains always non pathogenic . There is not a single risk or danger, neither for man nor for the environment, in the application of this method, which ensures only the cure of Borrelia reservoir ticks, without affecting or disturbing their natural balance . This method could be used successfully in the future.

Arkh Anat Gistol Embriol, 1982 Mar, 82(3), 56 - 9
{Effect of high-frequency ultrasound on the adaptive changes of cell resistance}; Plevinskis VP; Reparative and protective properties of the high frequency ultrasound (880 kgHz, 0.4--0.6 W/cm2) have been studied in the experiment performed on rabbits before and after actinomycin D administration (0.2-1.2 mg/kg) . RNA and total protein contents have been estimated in cytoplasm of ganglionic cells and in nuclei of photoreceptors . A positive effect of the ultrasound on actinomycin D-induced disorders in metabolic processes of the retina are proved to be weakly manifested . If the antibiotic is used in low concentrations, its inhibiting action can be eliminated or reduced with a subsequent ultrasound treatment of the eye . Simultaneous administration of the ultrasound and increased concentrations of actinomycin D enhances considerably development of certain degenerative changes in the retina . Preliminary ultrasound treatment (especially repeated) of the eye increases metabolic resistivity of retinal cells against the damaging effect of actinomycin D . It is manifested in less amount of cytochemical disorders, and when the inhibitor is applied in small doses-in their absence.

Antibiotiki, 1982 Mar, 27(3), 180 - 3
{Effect of streptomycin on antigenic properties of serum beta-lipoproteins}; Sluvko AL et al.; The antigenic properties of streptomycin compounds with heterologic beta-lipoproteids (beta-LP) of the donor blood serum were studied . beta-LP were isolated and then mixed with streptomycin sulfate in a dose of 10,000 and 50,000 micrograms/ml . 30 rabbits were immunized with such compounds . The control animals were treated with solutions of beta-LP and streptomycin alone . THe antisera collected from the animals were used in the reaction of precipitation and immunoelectrophoresis . Some physico-chemical properties of the preparations, such as pH and electrokinetic characteristics were studied . The comparative study with the use of the precipitation reaction showed that the immunochemical characteristics of heterologic beta-LP changed under the effect of streptomycin: the precipitation bands of the experimental antisera to the compounds of streptomycin with beta-LP differed from those of the control antisera to beta-LP in the quantitative and qualitative characteristics; in particular in the experiments with the antisera depletion a separate antigen was detected in beta-LP which formed under the effect of the antibiotic . The characteristic features of the reaction of precipitation were confirmed on the immunoelectrophoregrams . Addition of streptomycin to the solution of beta-LP induced no significant changes in pH of the compounds and their electrophoretic properties . The studies showed that the compounds of streptomycin with beta-LP had pronounced antigenic properties and their immunochemical characteristics significantly changed under the effect of the antibiotic.

Aust Fam Physician, 1982 Mar, 11(3), 194 - 5
Pertussis (whooping cough) . The specialist view; Beare TH; Pertussis is most severe in infants under one year of age in whom it can be a frightening disease . Early immunisation, supportive treatment, and prophylactic antibiotic therapy for susceptible contacts are dealt with by Dr Beare, who describes the condition from the specialist's viewpoint.

Br J Surg, 1982 Mar, 69(3), 151 - 2
Rectal strictures associated with the intra-uterine contraceptive device; Rogers K et al.; Two cases of stricture of the mid-rectum following extensive pelvic cellulitis due to the use of an intra-uterine contraceptive device (IUCD) are presented . The resulting dense circumferential extrarectal strictures failed to respond to treatment by proximal colostomy and antibiotic therapy and required difficult corrective resection . These are contrasted with an example of the more common upper rectal strictures associated with intraperitoneal sepsis of gynaecological origin, in this case pyosalpynx . Circumferential and transmural spread of inflammation tends to be limited by peritoneal reaction and the resulting strictures (which may be radiologically as severe as those in the mid-rectum) are often readily managed by simple removal of the source of infection . Thus, it appears that simple anatomical factors may be responsible for the differing pathologies seen in the two sites, and different management problems encountered within the two types of strictures.

Am J Physiol, 1982 Mar, 242(3), E137 - 45
Ionomycin stimulates secretion of catecholamines from cat adrenal gland and spleen; Carvalho MH et al.; Ionomycin, a polyether antibiotic, stimulated the secretion of catecholamines and dopamine beta-hydroxylase from perfused adrenal glands and {3H}norepinephrine ({3H}NE) from spleens of the cat . Release was calcium dependent, and strontium or barium did not substitute for calcium . Ionomycin failed to release {3H}NE from reserpinized spleens . High magnesium did not interfere in the ionomycin response, but lanthanum and manganese blocked it . Ionomycin response that was pH dependent was not affected by potassium depolarization . The secretory response to ionomycin was enhanced when both glycolysis and oxidative metabolism were inhibited . It is concluded that ionomycin introduces calcium into the chromaffin cells and adrenergic nerve terminals to cause the secretory response and that a rise in intracellular calcium may be an adequate stimulus for secretion.

J Thorac Cardiovasc Surg, 1982 Mar, 83(3), 363 - 71
Growth of lung cancer in a human tumor clonogenic system; Kitten CM et al.; The human tumor clonogenic assay system has enabled human cancer cells to be grown in vitro and has the potential of providing chemosensitivity results in a manner much like bacterial antibiotic sensitivities . The in vitro growth of human lung cancer cells using this assay has not been previously reported . Over the past 2 years, 3,100 specimens have been plated by means of the two-layer agar technique as developed by Hamburger and Salmon, 302 of which were primary or metastatic lung tumors . Histologic, karyotypic, and nude mice studies confirmed that the colonies were composed of tumor cells . Growth rates (significant growth being greater than or equal to 5 colonies per plate) and plating efficiencies (the number of colonies grown per number of nucleated cells plated) were tabulated for each lung tumor cell type for primary, metastatic, and malignant pleural and pericardial fluids . The average overall growth rate was 199 of 302 (66%)--17 of 19 (90%) large cell carcinomas, 46 of 71 (65%) oat cell carcinomas, 57 of 91 (63%) adenocarcinomas, (* = p less than 0.05 when compared to large cell carcinomas) *40 of 68 (59%) squamous cell carcinomas, *and 39 of 53 (74%) of an undetermined cell type were grown . The average plating efficiency was 0.0236% . In primary tumors, large cell carcinomas had a plating efficiency of 0.0348%, adenocarcinoma 0.0247%, *oat cell 0.0224%, *and squamous cell 0.0113%.* It was concluded that lung tumor cells can be grown in vitro from 66% of lung tumor specimens . The highest growth rates and plating efficiencies were found in large cell carcinomas and the lowest rates in squamous cell carcinomas . This technique may provide a means of testing for the sensitivity of patients' lung tumor cells to various chemotherapeutic agents.

J Am Vet Med Assoc, 1982 Mar 1, 180(5), 537 - 41
Treatment of canine actinomycosis; Hardie EM et al.; Sixteen cases of actinomycosis seen at the University of Georgia were reviewed . Treatment in 15 cases consisted of long-term antibiotic therapy combined with lavage and drainage of the affected area . Surgical debridement was used in several cases . Treatment was successful in 12 cases.

Postgrad Med, 1982 Mar, 71(3), 220 - 3
Mediastinal abscess secondary to vertebral osteomyelitis; Benezra C et al.; A 29-year-old man with complaints of pain in the low back, both flanks, and midepigastrium was found to have vertebral osteomyelitis . Mediastinal abscess was also diagnosed on the basis of findings on chest x-ray film, thoracic ultrasonography, thoracentesis, and cultures of pleural fluid . Antibiotic therapy was begun, and open drainage with rib resection was performed . After six weeks of treatment, the patient was free of symptoms . We believe this is the first report of mediastinal abscess secondary to vertebral osteomyelitis in an adult since the advent of antibiotics.

J Ethnopharmacol, 1982 Mar, 5(2), 149 - 61
Anti-reproductive and other medicinal effects of Tropaeolum tuberosum; Johns T et al.; Tropaeolum tuberosum is an edible-tuber-producing cultigen of the Andes mountains . Historical beliefs relating to the effects of this species on human reproductive potential continue to the present day . T . tuberosum subsp . tuberosum contains p-methoxybenzylglucosinolate as its major secondary metabolite . The putative anti-aphrodisiac activity of T . tuberosum was examined in male rats fed a diet containing tubers of this taxon . Experimental animals and controls showed equal capability in impregnating females, although animals fed T . tuberosum showed a 45% drop in their blood levels of testosterone/dihydrotestosterone . This decrease appears to be related to the presence of isothiocyanates in the tubers . Feeding studies of female guinea pigs and in vitro studies to test the 17 beta-estradiol binding inhibition of plant extracts and of pure isothiocyanates failed to substantiate any estrogenic activity of these taxa . However, preliminary results suggest that N, N-di-(methoxy-4-benzyl)thiourea competitively inhibits estradiol binding and may have estrogenic activity . The antibiotic, insecticidal, nematocidal and diuretic properties of isothiocyanates substantiate several of the uses of T . tuberosum in Andean folk medicine.

Rev Infect Dis, 1982 Mar-Apr, 4(2), 517 - 27
Comparison of trimethoprim-sulfamethoxazole with ampicillin in acute infectious exacerbations of chronic bronchitis: a double-blind crossover study; Chodosh S et al.; Two separate acute bacterial exacerbations of chronic bronchitis or chronic asthmatic bronchitis were treated in 20 patients in a double-blind crossover study . One course of treatment consisted of 320 mg of trimethoprim (TMP) plus, 1,600 mg of sulfamethoxazole (SMZ) daily and the other of 2 g of ampicillin daily; each drug was given for 14 days . Patients were observed initially, twice a week during therapy, and weekly after therapy . Observations that were recorded included graded chest symptoms and physical findings, vital signs, pulmonary function, hematologic parameters, and objective sputum measurements (daily volume, purulence, differential quantitative cytology, quantitative bacterial counts, physical properties, levels of lactate dehydrogenase with its isoenzymes, levels of myeloperoxidase, and presence of deoxyribonucleic acid fibers) . Both antibiotic regimens were effective in resolving these acute bacterial exacerbations . Paired t-test analysis revealed few and minor differences between TMP-SMZ and ampicillin during therapy, although three patients did not complete TMP-SMZ therapy because of adverse reactions . However, the period between the two bacterial exacerbations was significantly longer after ampicillin therapy . Innovative in this investigation are the study design and the objective quantitative measurements of inflammatory response and bacterial populations in sputum.

Ophthalmic Surg, 1982 Mar, 13(3), 231 - 3
Bacterial contamination of donor corneas stored in McCarey-Kaufman medium; Christenson J et al.; A new method is presented for culturing eye bank corneas stored in McCarey-Kaufman (M-K) medium . Of 30 donor corneoscleral rims, each was cultured in three ways: a swab on the M-K medium, a swab of the cut edge, and by culture of a 0.2 micron filter through which an aliquot of solution had been passed and washed of any antibiotic . We found a much higher rate of positive cultures using the latter method than has previously been reported in the literature.

Antimicrob Agents Chemother, 1982 Mar, 21(3), 501 - 3
In vitro activity of N-formimidoyl thienamycin against 98 clinical isolates of Brucella melitensis compared with those of cefoxitin, rifampin, tetracycline, and co-trimoxazole; Gutierrez Altes A et al.; IN vitro susceptibilities of 98 isolates of Brucella melitensis to N-formimidoyl thienamycin, tetracycline, co-trimoxazole, rifampin, and cefoxitin were determined . N-Formimidoyl thienamycin showed good activity which was similar to those of tetracycline and rifampin and different from that of the other beta-lactam antibiotic tested (cefoxitin), which showed poor activity . Co-trimoxazole showed good activity.

Am J Med, 1982 Mar, 72(3), 396 - 400
Q fever endocarditis; Tobin MJ et al.; Despite a worldwide distribution of Coxiella burnetii, only single cases of Q fever endocarditis have been reported outside Great Britain and Australia . We present 10 patients; five were female, only four had a history of environmental exposure, and the mitral valve was involved as commonly as the aortic stenosis, and three patients had a prosthetic valve . We confirm the importance of hepatic involvement, thrombocytopenia and hypergammaglobulinemia as diagnostic features . Diagnosis was established by finding and elevated complement-fixing antibody to Phase I C . burnetii antigen . Tetracycline, with or without lincomycin or cotrimoxazole, was used in nine patients, and one patient received cotrimoxazole as as the sole antibiotic agent . Optimal duration of therapy is unknown . In one patient, relapse followed when treatment was stopped after 18 months . Valve replacement was necessary in five patients, because of hemodynamic problems . Five patients died, and the means survival is 36 months with a range of five to 66 months . We suggest that Q fever endocarditis is frequently missed, and we recommend clinicians to consider the diagnosis in all cases of culture-negative endocarditis.

Gan To Kagaku Ryoho, 1982 Mar, 9(3), 516 - 21
{Cardiotoxicity of daunorubicin and aclacinomycin A in patients with acute leukemia}; Haruyama H et al.; Anthracycline antibiotics are principal agents in the treatment of acute non-lymphocytic leukemia, although the usefulness are limited by their adverse side effects, especially by the cardiotoxicity . Aclacinomycin A (ACM) is known to be a new anthracycline antibiotic which has been isolated from Streptomyces galilaeus, and its cardiotoxicity on the experimental animal systems was reported to be more than 10 times lower than that of adriamycin . We investigated the cardiotoxicity of ACM on 29 patients with acute leukemia and compared it with daunorubicin (DNR) . The measurement of STI (PEP:LVET) has been recommended to be convenient method of assessing the anthracycline cardiotoxicity, but through out analytical study, QTC measurement was proved to be more valuable for the simple and rapid detection of the cardiotoxicity induced by the agents . In comparison with the QTCs in DNR and ACM, the cardiotoxicity of ACM was much lower than that of DNR, and the reversibility of ACM induced cardiotoxicity was much more rapid . Moreover, these effects were observed even in the patients treated with the maximum dose of DNR . Therefore, ACM was expected to be one of the agents of the first choice for the relapsed cases of acute leukemia, especially APL.

Antibiotiki, 1982 Mar, 27(3), 173 - 6
{Use of agar diffusion method for separate determination of concentration of streptomycin and rifampicin in the blood in the presence of isoniazid}; Zeliger LR et al.; Conditions for determination of streptomycin and rifampicin in the blood serum on their combined use, as well as in the presence of isoniazid are described . For determination of the blood levels of streptomycin administered in combination with rifampicin it is recommended tat a variant of Bac . mycoides 537 resistant to rifampicin be used . When the rifampicin levels are determined in undiluted serum, the value obtained should be multiplied by 1.4 . When a 2-fold dilution of the serum is used, the value is multiplied by 1.15 . This provides an indicator maximally close to the real content of the antibiotic in the blood serum.

J Immunol, 1982 Mar, 128(3), 1334 - 40
Biosynthesis and processing of a human T lymphocyte antigen; Bergman Y et al.; The biosynthesis and processing of Leu-1, a human T lymphocyte antigen, has been studied with the use of a monoclonal antibody . This molecule exists on the cell surface as a 67,000 m.w . glycoprotein . Through a series of pulse-labeling studies, in conjunction with the use of the antibiotic tunicamycin and the enzyme Endo-H, the details of glycosylation, processing, and deposition at the cell membrane were examined . The protein backbone of the molecule is 58,000 m.w . High-mannose sugars are added to asparagine residues during synthesis . Within 20 min, these high mannose sugars are converted to complex type carbohydrates, including fucose . The fully processed glycoprotein appears at the cell surface within 30 min after synthesis . This sequence of events is similar to that for other cell surface glycoproteins, including HLA and vesicular stomatitus virus glycoprotein.

Can J Microbiol, 1982 Mar, 28(3), 311 - 7
Catabolite repression in Streptomyces venezuelae . Induction of beta-galactosidase, chloramphenicol production, and intracellular cyclic adenosine 3',5'-monophosphate concentrations; Chatterjee S et al.; Chloramphenicol production was studied in cultures of Streptomyces venezuelae growing in a simple buffered medium with ammonia as the nitrogen source and glucose, lactose, or a glucose-lactose mixture as the sole source of carbon . With each carbon source the antibiotic was formed during growth . In the glucose-lactose medium, the production pattern was biphasic; a marked decrease in the rate of synthesis was associated with depletion of glucose from the medium and a corresponding diauxie pause in growth . Cells of S . venezuelae contained an inducible beta-galactosidase . Induction by lactose was suppressed by glucose . Measurement of the concentration of intracellular adenosine 3',5'-cyclic monophosphate during growth of cultures with glucose or a glucose-lactose mixture as the source of carbon showed no appreciable changes coinciding with depletion of glucose or the onset of chloramphenicol biosynthesis . It is concluded that the cyclic nucleotide does not mediate selective nutrient utilization or control antibiotic biosynthesis in this organism.

J Gen Physiol, 1982 Mar, 79(3), 411 - 36
Alamethicin channels incorporated into frog node of ranvier: calcium-induced inactivation and membrane surface charges; Cahalan MD et al.; Alamethicin, a peptide antibiotic, partitions into artificial lipid bilayer membranes and into frog myelinated nerve membranes, inducing a voltage-dependent conductance . Discrete changes in conductance representing single-channel events with multiple open states can be detected in either frog node or lipid bilayer membranes . In 120 mM salt solution, the average conductance of a single channel is approximately 600 pS . The channel lifetimes are roughly two times longer in the node membrane than in a phosphatidylethanolamine bilayer at the same membrane potential . With 2 or 20 mM external Ca and internal CsCl, the alamethicin-induced conductance of frog nodal membrane inactivates . Inactivation is abolished by internal EGTA, suggesting that internal accumulation of calcium ions is responsible for the inactivation, through binding of Ca to negative internal surface charges . As a probe for both external and internal surface charges, alamethicin indicates a surface potential difference of approximately -20 to -30 mV, with the inner surface more negative . This surface charge asymmetry is opposite to the surface potential distribution near sodium channels.

Biofizika, 1982 Mar-Apr, 27(2), 331 - 3
{Change of current-voltage characteristics of amphotericin B ion channels accompanying its incorporation into the membrane}; Feigin AM et al.; Non-linearity of amphotericin B current-voltage characteristics is determined by means of the third harmonic generated in the membrane . A change of the sign of non-linearity is revealed during incorporation of antibiotic molecules into a membrane, i . e . the incorporation is not a simple increase of the number of similar ionic channels in the membrane.

Eur J Biochem, 1982 Mar, 123(1), 127 - 31
Two-dimensional NMR spectroscopy of siomycin A . Proton--carbon-13 chemical shift correlation; Clayden NJ et al.; A trial application of a recent two-dimensional nuclear magnetic resonance experiment to the polypeptide antibiotic siomycin A is described . Proton--carbon-13 chemical shift correlation measures the proton and carbon-13 chemical shift for each directly bonded CH group in a molecule, in a single experiment . The resultant map of correlated chemical shifts enables the carbon-13 spectrum to be assigned directly from the known proton shifts, and allows individual proton signals to be identified without problems of overlap . The signal-to-noise ratio available from such techniques should enable their application to aqueous protein solutions using currently available high-field spectrometers.

Mol Biochem Parasitol, 1982 Mar, 5(3), 173 - 87
Identification and characterisation of two N-acetylglucosaminyltransferases associated with Trypanosoma Brucei microsomes; Rovis L et al.; Microsomes forom Trypanosoma brucei contain glycosyltransferases able to incorporate N-{14C}acetylglucosamine into two different types of acceptors . A first transferase catalyzes the transfer of N-{14C}acetylglucosamine 1-phosphate from uridine diphosphate N-{14C}acetylglucosamine into dolichol monophosphate . The enzymatic activity requires Mn2+, is time and temperature dependent, has an optimum pH of 7.4 and is completely inhibited by the antibiotic tunicamycin . Exogenous dolichol monophosphate enhances the glycosyltransferase activity . The kinetics of incorporation are characterized by a Km of 2.6 microM for uridine diphosphate N-acetylglucosaminyltransferase are comparable to those reported for the first enzyme of the dolichol cycle described in several eukaryotes . N-Acetyl-glucosaminylpyrophosphoryl-dolichol is essentially the only product of the reaction . A second type of activity which is responsible for the direct transfer of N{14C}acetylglucosamine from uridine diphosphate N{14C}acetylglucosamine into several endogenous polypeptide acceptors, is also associated with T . brucei microsomes . The reaction, which might be due to more than one enzyme, is dependent on Mn2+, but differs from the other transferase in all other characteristics . Time course and optimal temperature are different, and the optimum pH is 6.5 . The reaction is independent of the external addition of dolichol monophosphate and tunicamy cin has no inhibitory effect on the enzymatic activity . AKm of 1.6 microM was calculated fr uridine diphosphate N-acetylglucosamine.

Vopr Virusol, 1982 Mar-Apr, 27(2), 166 - 9
{Effect of amphotericin B on the activity of synthetic polyribonucleotide interferon inducers}; Vil'ner LM et al.; The authors investigated the intensity of interferon production and the degree of the associated antiviral resistance induced by double-stranded synthetic polyribonucleotide interferon inducers poly(G) . poly(C), poly(G, I) . poly(C) and poly(G, A) . poly(C) in chick embryo cell cultures, continuous diploid human fibroblasts and in mice in the presence of amphotericin B, a macrolide polyene antibiotic enhancing the permeability of plasma membranes for macromolecules . Amphotericin B was found to increase considerably the interferon-inducing and antiviral activity of the above polyribonucleotide complexes in those cell systems where they induced interferon production and antiviral resistance alone, without the antibiotic, but to a lower degree . Amphotericin B did not contribute to the activity of the complexes in those cell systems where they were inert alone . The importance of permeability of the plasma membrane for interferon induction is discussed, and a conclusion is reached that the inertness of the complexes under study in one cell system and their activity in the others are not associated with differences in the permeability of the plasma membranes of different cells for polyribonucleotide interferon inducers.

Cancer Res, 1982 Mar, 42(3), 999 - 1004
CC-1065 (NSC 298223), a novel antitumor agent that interacts strongly with double-stranded DNA; Li LH et al.; CC-1065, a novel antibiotic produced by Streptomyces zelensis, was active against several experimental tumors in vivo and a broad spectrum of human tumor cells in vitro . This report describes its biological and biochemical effects of L1210 leukemia cells . CC-1065 is one of the most cytotoxic agents known . The concentrations required for a 50 and 90% inhibition of cell growth are 0.02 and 0.05 ng/ml, respectively . It is about 400 times more cytotoxic than was Adriamycin . The action of CC-1065 is rapid and is dose and time dependent . CC-1065 inhibits DNA synthesis much more than it inhibits RNA and protein synthesis . The concentrations required for a 50% inhibition of DNA synthesis and RNA synthesis are 4 to 6 and 45 to 60 ng/ml, respectively . Although the drug inhibition of DNA synthesis cannot completely account for its cytotoxic effects on L1210 cells, these results, along with those generated by other investigators, suggest that the inhibition of DNA synthesis represents a major mode of action of CC-1065 . CC-1065 inhibited both thymidine kinase and DNA polymerase alpha activities, but the effect on highly purified DNA polymerase alpha was more pronounced . At 1 microgram/ml, CC-1065 inhibited more than 70% of the enzyme activity . In order to elucidate the mechanism of inhibition of DNA polymerase alpha, the interaction between CC-1065 and DNA was investigated . The studies with thermal melting of DNA and difference circular dichroism measurement indicate that CC-1065 is one of the strongest DNA-binding agents . It induced an increase in thermal melting temperature of calf thymus DNA by at least 31 degrees . The circular dichroism studies also reveal that CC-1065 binds only to double-stranded DNA but not to heat-denatured DNA or yeast RNA . These observations were supported by those obtained with two other experimental approaches . CC-1065 also appeared to interact with proteins, but the interaction was weak and reversible.

C R Seances Acad Sci III, 1982 Feb 22, 294(8), 371 - 4
{Differential effect of tunicamycin on glycosylation of cell surface glycoproteins from chick fibroblasts during embryo development (author's transl)}; Vernay M et al.; The antibiotic tunicamycin inhibits glycosylation of proteins as demonstrated by the inhibition of the incorporation of 14C glucosamine glycoproteins of chick embryo fibroblasts at two stages of development . Fibroblasts from 8-day embryos are more sensitive to TM treatment than 16-day embryos . This differential effect is directly related to the level of N- and O-glycosidically linked glycoproteins . This ratio decreased within development . Moreover, a parallelism is observed between inhibition of cell surface glycoprotein glycosylation by TM and adhesion properties of treated cells, suggesting that N- glycosidically linked glycoproteins might be involved in cell adhesivity.

Nouv Presse Med, 1982 Feb 4, 11(5 Pt 2), 373 - 6
{Tissue distribution of mezlocillin (author's transl)}; Singlas E; Substantial amounts of mezlocillin are rapidly distributed in a wide range of tissues . After intravenous administration of doses ranging form 2 to 5 g, concentrations therapeutically active against most sensitive organisms were obtained in bone, prostate, skin, muscle and liver, as well as in wound exudates, pleural exudates, sputum and bronchial secretions . Mezlocillin did not easily cross the blood-brain barrier with normal meninges, but CSF concentrations when the meninges were inflamed . The antibiotic also crossed the placenta.

Sem Hop, 1982 Feb 4, 58(5), 275 - 9
{Brucella melitensis endocarditis . Clinical and immunological features (author's transl)}; Bertrand A et al.; Five cases of Brucella melitensis endocarditis are reported . Common features included subacute course, enhanced humoral immunity, and deficient cellular immunity . Appropriate antibiotic therapy led to recovery in all cases . In two patients, valvular replacement was necessary.

Jpn J Antibiot, 1982 Feb, 35(2), 659 - 66
{Reproduction study on netilmicin . (4) Teratological study in rabbits (author's transl)}; Furuhashi T et al.; Teratological study on netilmicin (NTL), a new aminoglycoside antibiotic, was carried out in New Zealand White rabbits . NTL was administered intramuscularly from day 60 to day 18 of gestation at the dose levels of 12.5, 35 and 100 mg/kg . The decrease of food intake, water intake and depression of body weight were observed in the pregnant animals treated with 100 mg/kg of NTL . Body weight and tail length of fetuses were significantly decreased in the animals treated with 35 and 100 mg/kg compared with those in saline control or vehicle control groups . However, no dose-related changes or anomalies were detected in mortality, external, visceral and skeletal examinations of fetuses . Thus, it can be concluded that NTL has no adverse effect on rabbit fetuses.

Jpn J Antibiot, 1982 Feb, 35(2), 643 - 58
{Reproduction study on netilmicin . (3) Perinatal and postnatal study in rats (author's transl)}; Furuhashi T et al.; Perinatal and postnatal study on netilmicin (NTL), a new aminoglycoside antibiotic, was carried out in Sprague-Dawley rats (Slc : SD) . NTL was administered intramuscularly from day 17 of gestation throughout day 20 after delivery at the daily dose of 12.5, 25, 50 and 100 mg/kg . Water intake of pregnant and nursing dams was increased in the animals treated with 50 mg/kg or more of NTL . The increase of cecum weight was observed in F1 animals in all treated groups at 3 weeks of age . However, birth rate, suckling rate, weanling rate, body weight, postnatal development, behavior and reproductive function remained within normal ranges in all treated groups.

Jpn J Antibiot, 1982 Feb, 35(2), 630 - 42
{Reproduction study on netilmicin . (2) Fertility study in rats (author's transl)}; Furuhashi T et al.; Fertility study on netilmicin (NTL), a new aminoglycoside antibiotic, was carried out in Sprague-Dawley rats (Slc : SD) . NTL was administered intramuscularly to male rats at the daily dose of 12.5, 25, 50 and 100 mg/kg from 6 to 15 weeks of age for 9 weeks before mating and during the mating period, and to 10 weeks old female rats at the daily dose levels from day 14 before mating through day 7 after gestation . The increase of kidney weight at the dose of 12.5 mg/kg and more, the decreases of food intake and body weight were observed in treated male rats . The decreases of food intake and body weight were observed in female rats treated with the dose of 50 and 100 mg/kg . No dose-related changes were observed in mating and fertility ratios of parent animals, numbers of corpora lutea and implantations, fetal mortality, external, visceral and skeletal anomalies, body weight, body length and tail length of fetuses . Therefore, it can be concluded that maximum non-toxic dose level of NTL on rat fertility is 100 mg/kg.

Jpn J Antibiot, 1982 Feb, 35(2), 614 - 29
{Reproduction study on netilmicin . (1) Teratological study in rats (author's transl)}; Nomura A et al.; Teratological study on netilmicin (NTL), a new aminoglycoside antibiotic, was carried out in Sprague-Dawley rats (Slc : SD) . NTL was administered intramuscularly to female rats from day 7 to day 17 of gestation at the dosages of 12.5, 25, 50 and 100 mg/kg . The decrease of food intake at the dosage of 50 mg/kg and more, and the resultant depression of maternal body weight gain at the dosage of 100 mg/kg were observed in dams receiving NTL . The depression of fetal growth, such as body weight and ossification of the sternebrae and caudal vertebrae, were detected in animals treated with 50 and 100 mg/kg of NTL . However, NTL failed to induce the external, visceral and skeletal anomalies in fetuses . Also, NTL did not cause any significant changes in birth rate, suckling rate, weaning rate, body weight, postnatal development, behavior and reproductive performance in F1 . These results suggest that NTL has no adverse effect on rat fetuses and F1 generation at the dosage of 25 mg/kg or less.

Jpn J Antibiot, 1982 Feb, 35(2), 375 - 93
{Clinical studies of cefoxitin for the treatment of respiratory tract infections (author's transl)}; Suetsugu S et al.; A total of 42 patients who were suffering from respiratory tract infections were treated with cefoxitin, and the following results were obtained . 1 . Out of 32 patients clinically evaluated, excellent or good responses were observed in 30 patients (94%) . 2 . Presumed causative organisms were isolated in 14 patients . The organisms were eradicated in 11 patients and the eradication rate was 79% (11/14) . The number of the organisms decreased or unchanged in 1 patient each . In other 1 patient the pathogenic agent was replaced with other agents during the course of treatment . 3 . As for the side effects, skin eruption was observed in 3 patients . One patient received drugs other than cefoxitin concomitantly that might have caused the eruption . Another patient had an allergic history to many antibiotics . In 4 patients slight elevations of S-GOT and S-GPT were observed but improved soon after the completion of cefoxitin treatment . In 1 patient an elevation of serum creatinine was observed but this was not attributed to the administration of cefoxitin . 4 . From the results stated above, cefoxitin is considered to be a safe and effective antibiotic which can be one of the first-choice antibiotics for the treatment of respiratory tract infections.

Mol Biochem Parasitol, 1982 Feb, 5(2), 117 - 31
Trypanosoma brucei: effect of inhibition of N-linked glycosylation of the nearest neighbor analysis of the major variable surface coat glycoprotein; Strickler JE et al.; As an assay for the surface deposition of newly synthesized major variable surface coat glycoprotein (VSCG) we have treated intact Trypanosoma brucei cells with the cleavable cross-linking reagent dithiobis-(succinimidyl propionate) . Under appropriate conditions, surface VSCG is converted to oligomers of n not less than 8 . The oligomeric protein, apparent molecular weight greater than 4 x 10(5), does not migrate more than 1 to 2 mm into a 3-15% linear polyacrylamide gradient gel containing 0.1% sodium dodecyl sulfate, hence the appearance of newly synthesized radiolabeled protein in the top 2 mm of the gel indicates the translocation of VSCG from the site of synthesis to the surface and the gross establishment of normal interactions among the molecules . In addition, purified VSCG treated with the cross-linking reagent yielded a dimeric product on gel electrophoresis . To examine the role of N-linked carbohydrate in the translocation of the protein and in intermolecular interactions we have allowed trypanosomes to incorporate L-{14C} serine into protein in the presence of the antibiotic tunicamycin . Our results show that N-linked carbohydrate is not essential to the transfer of VSCG to the cell surface nor does its absence interfere with gross intermolecular interactions in the short term . On the other hand N-linked carbohydrate does appear to play an essential role in dimer formation.

Antimicrob Agents Chemother, 1982 Feb, 21(2), 241 - 7
Membrane transport of clindamycin in alveolar macrophages; Hand WL et al.; The use of antibiotics which can penetrate phagocytic cells and kill intracellular organisms is desirable in the treatment of chronic facultative bacterial infections . Recently, we reported that several antibiotics were selectively concentrated by rabbit alveolar macrophages . Clindamycin accumulation was especially marked . In the present study we evaluated the plasma membrane transport (initial uptake) of clindamycin in alveolar macrophages . The transport of clindamycin is an active process, as documented by requirements for cellular viability, elevated environmental temperature, metabolic energy, and establishment of the 40- to 50-fold cellular/extracellular gradient . Energy for membrane transport of the drug depended at least in part upon mitochondrial oxidative respiration and cell membrane Na-K pump activity . Kinetic analysis of active clindamycin transport revealed it to be saturable, with a high binding affinity (Km = 1 mM) and a high velocity of uptake (Vmax = 15.8 nmol/45 s per 10(6) cells) . Clindamycin uptake was not influenced by the presence of hexose or amino acids, but was inhibited by nucleosides (adenosine, puromycin) . Decreased clindamycin transport in the presence of puromycin was typical of competitive inhibition (increased Km, unchanged Vmax) . Conversely, competitive inhibition of adenosine transport by clindamycin was documented . Thus, clindamycin is transported into alveolar macrophages via the nucleoside system . The potential biological consequences of this unique antibiotic transport mechanism are of interest.

Vestn Khir Im I I Grek, 1982 Feb, 128(2), 48 - 50
{Active surgical treatment of suppurative wounds and acute suppurative diseases}; Abasov BKh et al.; Advantages of the active surgical treatment are convincingly shown by the analysis of results of the treatment of 122 patients with purulent wounds and acute purulent diseases by traditional methods (opening the suppurative focus, drainage of the wound with gauze tampons) or the active surgical method (initial surgical treatment of the purulent wound or focus, drainage with a plastic tube, fractional or permanent washing of the wound) in combination with antibiotic therapy, application of enzymatic, antienzymatic and immunological agents.

J Clin Microbiol, 1982 Feb, 15(2), 342 - 4
Simple, transparent medium for study of legionellae; Johnson SR et al.; A simple medium containing yeast extract, phosphate, and hemin as major components has been formulated for the study of legionellae . The medium supports the growth of a wide range of clinical and environmental isolates, with plating efficiencies comparable to those of charcoal-yeast extract agar . In addition, it does not contain activated charcoal or other components which may be associated with adverse reactions in humans . The medium is buffered and transparent; therefore, it would be suitable for genetic studies, production of biological reagents such as antigens and skin tests for human use, and antibiotic susceptibility assays.

J Pharm Sci, 1982 Feb, 71(2), 197 - 200
Mechanism of action of granaticin: inhibition of ribosomal RNA maturation and cell cycle specificity; Heinstein P; Granaticin, an antibiotic produced by Streptomyces species was found to be cytotoxic (ED50 3.2 microgram/ml) against human oral epidermoid carcinoma (KB) cells . AT ED50 concentrations RNA synthesis was inhibited to the greatest extent . Prelabeling of RNA in KB cells, followed by addition of granaticin (2.13 microgram/ml) showed that ribosomal RNA maturation was inhibited . The inhibition of the formation of functional ribosomal RNA was determined by sucrose gradient centrifugation and showed that the accumulation of 45S preribosomal RNA was dependent on granaticin concentration and on the time granaticin was in contact with the KB cells . The effect of granaticin (6.3 microgram/ml) on KB cells in the different cell cycle phases showed preferential inhibition (93%) of cell survival in the G2 phase . However, RNA synthesis was only 20% inhibited by granaticin in KB cells in the G2 phase . From these results, it was concluded that ribosomal RNA maturation was not the only site of action of granaticin toxicity.

Int J Clin Pharmacol Ther Toxicol, 1982 Feb, 20(2), 92 - 4
Pharmacokinetics of intravenous and intraperitoneal cefuroxime during peritoneal dialysis; La Greca G et al.; We investigated the pharmacokinetics of cefuroxime sodium, a new parenteral beta-lactam antibiotic, in 15 patients with stable chronic renal failure during intermittent peritoneal dialysis (IPD) . Eight patients were administered 1 g cefuroxime as an intravenous bolus 1 h before the start of dialysis . Mean plasma levels of cefuroxime fell from 80 mcg/ml at 1 h to 40 mcg/ml at 6-8 h . At 24 h, concentrations were higher than 20 mcg/ml . In peritoneal fluid cefuroxime reached 16.7 mcg/ml at 1 h and 7.55 mcg/ml at 6 h . Seven patients received cefuroxime added to the dialysis solution at a dose of 2.5 g/10 liters . After 6 h of dialysis, cefuroxime reached plasma levels of 60 mcg/ml; after 24 h, concentrations were 37.5 mcg/ml . These results demonstrate that cefuroxime, administered by the i.v . route, easily diffuses from blood to peritoneal fluid and, from peritoneal fluid to blood when added to the dialysis solution . In both cases concentrations reached by cefuroxime are sufficient to treat peritoneal infections associated with peritoneal dialysis.

Am Fam Physician, 1982 Feb, 25(2), 163 - 7
Treatment priorities for septic shock; Ellenbogen C; Septic shock is an emergency that is best treated by establishing priorities beforehand . The first priority is early recognition . The earliest recognizable clinical presentation is fever and hyperventilation . The second priority is augmenting normal compensatory mechanisms by intravenous infusion of crystalloid, with measurement of the response so that vasoactive drugs can be instituted as needed . The third priority is selected antibiotic therapy and drainage of pus . The fourth is corticosteroid therapy if the patient's response has been suboptimal.

J Thorac Cardiovasc Surg, 1982 Feb, 83(2), 194 - 204
Lye ingestion . Clinical patterns and therapeutic implications; Oakes DD et al.; Conventional treatment of caustic esophagitis consists of early endoscopy to the first site of injury followed by antibiotic and steroid therapy, with early mechanical dilatation to prevent stricture formation . The failure of this approach in two recent patients led us to review our overall experience with the management of patients who had ingested lye or other caustic substances . Of 42 patients treated at the Santa Clara Valley Medical Center between 1970 and 1980, seven sustained severe esophageal burns . All had intractable strictures despite steroids, antibiotics, and, in three cases, attempts at dilatation . We conclude that patient survival should not be jeopardized by overly aggressive attempts to salvage an extensively damaged esophagus . Such attempts will probably prove both futile and dangerous, and effective re-establishment of oral-intestinal continuity is now possible by a variety of techniques.

Ann Surg, 1982 Feb, 195(2), 137 - 45
Factors in management of acute cholangitis; Thompson JE Jr et al.; Ninety episodes of acute cholangitis in 66 patients have been analyzed . In 71% of the episodes, an operation was performed . Eight deaths occurred, for a patient mortality rate of 12% . Sixty-seven per cent of the operations were performed after at least 72 hours of antibiotic therapy, whereas only 17% had to be done as life-threatening emergencies within 24 hours of admission to the hospital . Although 86% of the operative deaths occurred in the group operated on more than 72 hours after admission, this was not statistically significant . However, death did correlate with failure to respond to antibiotic therapy (p less than 0.001) irrespective of time of operation . Biliary cancer and congenital lesions were etiologic for 31% of the operative cases in this series, but were responsible for 71% of the postoperative deaths (p less than 0.05) . We conclude that acute cholangitis has a wide spectrum of severity and that most cases will respond to antibiotic therapy, affording the surgeon the luxury of operating in an elective fashion . Moreover, acute cholangitis complicated by failure to respond to antibiotic therapy is more likely to occur in biliary cancer and congenital lesions, and subsequently will have a poorer prognosis.

J Antibiot (Tokyo), 1982 Feb, 35(2), 230 - 4
Potentiation of antifungal effect of amphotericin B by squalene, an intermediate for sterol biosynthesis; Masuda A et al.; The antifungal effect of a polyene antibiotic amphotericin B (AMB) was almost completely abrogated by exogenous addition of 0.1 microgram/ml ergosterol in the medium . The cytocidal effect of AMB on Saccharomyces cerevisiae was synergistically enhanced when cultured for more than 4 hours with squalene, an obligatory intermediate molecule for sterol formation . However, we could not find significant increase in cellular level of ergosterol content in the yeast cells fed with squalene.

Geriatrics, 1982 Feb, 37(2), 132 - 7
The latest word on coping with infections in the elderly; Oster HA; Elderly individuals are particularly susceptible to hospital-acquired infections, partly as a result of underlying chronic conditions that predispose to infection and influence prognosis . Prior antibiotic therapy may allow for colonization with resistant organisms and thus increase the risk of the development of bacterial pneumonia and other infections.

Jpn J Antibiot, 1982 Feb, 35(2), 421 - 8
{Clinical studies of 9,3"-diacetylmidecamycin in pediatric field (author's transl)}; Yanagisawa K et al.; Clinical trials of 9,3"-diacetylmidecamycin (MOM), a new macrolide antibiotic were carried out on 46 pediatric patients of 1 month to 11 years old with infections (acute pharyngitis 12, acute tonsillitis 1, acute bronchitis 14, asthmatic bronchitis 10, acute pneumonia 1, primary atypical pneumonia 2, Mycoplasma pneumonia 4 and pertussis 2) . As a rule, MOM was given orally at a daily dose of 20 approximately 40 mg/kg divided into 3 times . The clinical results were excellent in 5 patients, good in 21, fair in 7 and poor in 13 and the efficacy rate was 56.5% . Side effects were observed in 4 patients (diarrhea, exanthema, urticaria and eosinophilia, 1 patient respectively) . MOM is easy to take and a useful antibiotic for treating patients with bacterial infections, in particular, respiratory tract infection caused by Mycoplasma pneumoniae.

Clin Nucl Med, 1982 Feb, 7(2), 71 - 4
Radiogallium scan in P . carinii pneumonia; Parthasarathy KL et al.; A gallium scan performed on a patient with fever of unknown origin (FUO) revealed an abnormal uptake of radiotracer in the lungs despite negative chest roentgenographic examination and other routine diagnostic studies . Subsequent lung biopsy results confirmed the presence of Pneumocystis (P.) carinii infection . A repeat gallium scan obtained following appropriate antibiotic therapy was essentially normal . The importance of radiogallium scanning in an immunosuppressed patient with FUO is emphasized.

Antimicrob Agents Chemother, 1982 Feb, 21(2), 268 - 73
Gentamicin inactivation by piperacillin or carbenicillin in patients with end-stage renal disease; Thompson MI et al.; Possible antibiotic inactivation was studied in 12 subjects with end-stage renal disease who were undergoing thrice-weekly hemodialysis . The study was a randomized three-way crossover . Subjects received (i) gentamicin as a single intravenous dose of 2 mg/kg, (ii) 4 g of piperacillin intravenously every 12 h for four doses or 2 g of carbenicillin intravenously every 8 h for six doses, and (iii) gentamicin as described in (i) plus piperacillin or carbenicillin as described in (ii) . Subjects were studied on their off-dialysis days, and each treatment phase was separated by a 3-week wash-out period . Gentamicin was inactivated to a greater extent by carbenicillin than by piperacillin (P less than 0.05) . In the six subjects in the carbenicillin group, the terminal elimination-phase half-life (t 1/2 beta) of gentamicin was 61.6 h when gentamicin was administered alone, and it was 19.4 h when gentamicin was administered with carbenicillin . In six subjects in the piperacillin group, the mean t 1/2 beta of gentamicin when gentamicin was given alone was 53.9 h, and it was 37.7 h when gentamicin was given with piperacillin . The inactivation rate constant (ki) of gentamicin was 0.0251/h for the carbenicillin group and 0.0064/h for the piperacillin group, demonstrating that carbenicillin inactivated gentamicin for time faster than did piperacillin . No inactivation of either beta-lactam could be measured . Control samples verified that no in vitro inactivation occurred.

Antibiotiki, 1982 Feb, 27(2), 87 - 92
{New species, Actinomadura fulvescens sp . nov . and Actinomadura turkmeniaca sp . nov . and their antagonistic properties}; Terekhova LP et al.; Two new species of Actinomadura isolated from soil samples of the Turkmen SSR, i.e . Actinomadura fulvescens sp . nov . and Actinomadura turkmeniaca sp . nov . are described . The first species is characterized by formation of short (1-2 turns) spiral spore chains, smooth spores, scanty white aerial mycelium, colourless or yellowish substrate mycelium on synthetic media and brownish-yellow substrate mycelium and soluble pigment of the same colour on organic media . No melanoid pigment is secreted . The type culture is designated as INA 3321 . The cultures of A . fulvescens show antibiotic activity . A . turkmeniaca is characterized by formation of short straight or spiral spore chains, smooth spores, scanty white aerial mycelium, substrate mycelium and soluble pigment of pinkish-violet colour, absence of melanoid pigment . The type culture is designated as INA 3344 . The strains of this species have low antibiotic activity . The study on the use of carbon sources by the representatives of 7 species (9 strains) of Actinomadura showed that the majority of the cultures (5 species, 7 strains) produced no growth on the Pridham and Gottlieb medium (ISP-9) with various carbon sources, including glucose . Possibly this medium cannot be used as the main medium for investigation of the spectrum of carbohydrate consumption in Actinomadura.

J Gen Microbiol, 1982 Feb, 128(Pt 2), 361 - 9
Envelope protein synthesis and inhibition of cell division in Escherichia coli during inactivation of the B subunit of DNA gyrase; Herrero E et al.; The rates of synthesis of inner and outer membrane proteins of Escherichia coli K12 during inhibition of cell division have been studied . When cell division was inhibited, either by treatment of wild-type cells with the antibiotic clorobiocin (an inhibitor of the B subunit of DNA gyrase) or by a temperature shift of a gyrB-ts mutant, a 40% reduction in the rate of synthesis of total outer membrane protein relative to that of the inner membrane was observed . When a gyrB-ts mutant was shifted to high temperature under conditions which allowed continued cell division, this large reduction in the rate of synthesis of outer membrane protein relative to inner membrane protein was not observed . In contrast to the results obtained with clorobiocin, inhibition of cell division by the beta-lactam antibiotic cefuroxime did not cause any detectable disturbance in the rate of synthesis of either inner or outer membrane protein . This demonstrates that inhibition of septum formation per se does not perturb synthesis of envelope protein . The data obtained are consistent with a model in which the rate of synthesis and therefore expansion of outer membrane is one of many conditions which must be satisfied before septum formation can occur . The results are discussed in relation to such a model, and to previous findings which have shown that the rate of synthesis of outer membrane proteins displays a linear mode with an abrupt doubling in rate at a discrete point in the cell cycle.

Antibiotiki, 1982 Feb, 27(2), 147 - 50
{Mutagenesis in Streptomycete cultures exposed to bleomycin}; Lapchinskaia OA et al.; Mutagenic properties of bleomycin, an antitumor antibiotic were studied with respect to 2 species of streptomycetes producing practically important antibiotics . A multifold increase in the frequency of prototrophic revertants among the survivors of strains His- and Met- of Actinomadura carminata exposed to bleomycin was observed . Bleomycin was effective in induction of various morphological mutants, and auxotrophs at a high survival rate of the spores of Str . cremeus var . tobramycini, a tobramycin-producing organism . It was shown with the method of subsequent mutagenesis that the efficacy of induction of morphological and auxotrophic mutants in germinating spores of Actinomadura carminata, a carminomycin-producing organism by bleomycin in a concentration of 100 micrograms/ml and an exposure time of 5 minutes was much higher that in the latent spores . The mutagenic effect of bleomycin is comparable with that of ionizing radiation.

Exp Hematol, 1982 Feb, 10(2), 178 - 86
Correlation between LPS-induced mitogenic and virogenic activities in mouse spleen cell cultures; Hornstein A et al.; The present study provides direct evidence for a correlation between mitogenicity and induction of type C particles (virogenic activity) in cultures stimulated by LPS . This evidence is based on the following observations: 1) The complex of the antibiotic polymyxin B with LPS (LPS-PB) inhibits mitogenicity and virogenic activity in spleen cell cultures from BALB/c mice, but does not inhibit the generation of colony stimulating factor (CSF) from such cultures; 2) CBA/N, a genetically-defective mouse strain in its mitogenic response to LPS, was also defective in virus induction by LPS, but generated high levels of LPS-induced CSF.

Cancer Res, 1982 Feb, 42(2), 583 - 9
Tissue distribution, molecular profile, and shedding of a cytoplasmic antigen identified by the monoclonal antibody 465.12S to human melanoma cells; Natali PG et al.; The mouse immunoglobulin G2 monoclonal antibody (MoAb) 465.12S reacts with a cytoplasmic antigen present in human melanoma cells but not detectable in melanocytes . Indirect immunofluorescent staining of a large number of surgically removed normal adult and fetal tissues with the MoAb 465.12S detected the cytoplasmic antigen in epithelial cells from several organs . The intensity of staining was greater in adult tissues than in the corresponding fetal tissues . Furthermore, the MoAb 465.12S stained nearly all of the surgically removed tumors tested but did not stain many of the normal tissues from which they originated . In almost all cases, the intensity and frequency of staining wa greater for tumor cells than for corresponding normal tissues . From cultured carcinoma and melanoma cells, the MoAb 465.12S immunoprecipitated four glycopolypeptides with molecular weights of 94,000, 75,000, 70,000, and 25,000 . Incorporation of 3H-labeled sugars into the various components of the cytoplasmic antigen revealed that the M.W . 75,000 component was unusual in that it contained only glucosamine and mannose . The antigenic determinant defined by the MoAb 465.12S appears to be protein rather than carbohydrate in nature since it is heat sensitive and is expressed on the antigens synthesized by cells in presence of tunicamycin . Analysis of the spent culture medium of carcinoma and melanoma cell lines revealed that the cytoplasmic antigen is readily shed by these cells and consists of a major M.W . 94,000 and a minor M.W . 72,000 component . Treatment of cultured melanoma cells with the antibiotic tunicamycin showed that glycosylation of the cytoplasmic antigen is required for its shedding and/or stability in the spent culture medium.

Cancer Treat Rep, 1982 Feb, 66(2), 311 - 6
Inhibition of cardiac guanylate cyclase by doxorubicin and some of its analogs: possible relationship to cardiotoxicity; Lehotay DC et al.; The anthracycline antibiotic doxorubicin induces a variety of cardiotoxic effects . We have recently demonstrated that this drug also causes a selective inhibition of rat and human cardiac guanylate cyclase activity in vitro . In the present study, we examined the effect of 30 analogs of doxorubicin on cardiac guanylate cyclase activity . Structural modifications of these anthracycline antibiotics were found to alter their effect on rat cardiac guanylate cyclase activity, N-Substitutions on the sugar moiety eliminated the inhibitory action observed with the parent compound . Long-chain hydrocarbon substitutions in place of the methylketone side chain had a similar effect . Removal or substitution of the C-4 methoxy group had little or no effect on the ability of these compounds to modify guanylate cyclase activity . Substitutions of the C-9 side chain by a hydrazone derivative resulted in compounds that stimulated the enzyme . All of the anthracenedione derivatives were inhibitory . A comparison of the inhibitory effect of some of these anthracycline derivatives on in vitro cardiac guanylate cyclase activity with their cardiotoxic potency suggests a possible relationship between these two parameters.

Biochim Biophys Acta, 1982 Jan 22, 684(2), 291 - 4
The effect of amphotericin B on the permeability of lipid bilayers to divalent trace metals; Aggett PJ et al.; In this study amphotericin B released the divalent trace metals Zn2+, Co2+, Cu2+, Ni2+, Mn2+, Fe2+, Cd2+ and Pb2+ from multilamellar liposomes containing cholesterol . This observation is consistent with amphotericin B channels being permeable to these metals, and it is proposed, therefore, that the antibiotic may be useful in investigating the metabolism of these elements.

Biochim Biophys Acta, 1982 Jan 22, 684(2), 233 - 40
The effect of amine structure on complexation with lasalocid in model membrane systems . I . Identification of charged complexes in lipid bilayer membranes; Kinsel JF et al.; The electrical properties of X-537A (lasalocid) doped lipid bilayer membranes were studied in the presence of a series of nine biogenic amines which contain beta-phenylethylamine as the basic structural unit . The ionophore antibiotic was found to form charged complexes within the membrane during the transport of some of the amines . The dependence of membrane conductance on the concentration of ionophore and amine was studied . The amines are divided into three classes according to the nature of the complexes formed: (1) charged complex involving two ionophores (phenylephrine, metanephrine, and amphetamine); (2) charged complex containing three ionophores (dopamine, norepinephrine and epinephrine); and (3) no charged species formed (p- and m-tyramine and beta-phenylethylamine).

Lancet, 1982 Jan 16, 1(8264), 132 - 4
Treatment of pyogenic liver abscesses by percutaneous needle aspiration; Berger LA et al.; Fifteen patients with solitary or multiple pyogenic liver abscesses diagnosed by ultrasound examination were treated by percutaneous aspiration under ultrasound guidance . The pus obtained was cultured immediately for aerobic and anaerobic organisms and appropriate antibiotic therapy was started . Anaerobic organisms were grown from this pus in nine patients . All patients improved after the aspiration and, apart from further aspirations in two cases, all abscesses healed without further intervention . No patient died from liver abscess or as a result of treatment . The technique is simple and harmless and is the method of choice for diagnosing and treating patients with pyogenic liver abscesses.

J Biol Chem, 1982 Jan 10, 257(1), 95 - 103
Intracellular glycosylation of vitellogenin in the liver of estrogen-stimulated Xenopus laevis; Gottlieb TA et al.; Pulse-chase experiments measuring the rates of incorporation of radiolabeled glucosamine and galactose into intracellular vitellogenin show that glycosylation of this multicomponent protein occurs in a Golgi-enriched fraction isolated from homogenized liver slices . No apparent role of the rough endoplasmic reticulum in this process was demonstrable . Kinetics of the intracellular translocation of glycosylated vitellogenin indicate that the galactosylated intermediate is secreted more rapidly than the glucosamine-labeled precursor . This was corroborated by measuring the rates of accumulation of various pulse-labeled forms of vitellogenin in the chase medium . In addition, a negligible amount of mannose was incorporated into intracellular or secreted vitellogenin . The antibiotic tunicamycin was shown to inhibit {3H} glucosamine incorporation into microsomal vitellogenin by 70%, without any significant effect on the synthesis of the protein backbone . In addition, nonglycosylated vitellogenin showed normal secretion kinetics . After suitable pretreatment with the antibiotic followed by a labeling period in tunicamycin-free medium, mannose was still not incorporated into vitellogenin, whereas glucosamine behaved in a typical manner . In contrast to this finding, gas-liquid chromatography of the alditol acetate derivatives of the neutral hexoses of vitellogenin showed that mannose was indeed a major component of the vitellogenin oligosaccharide side chain . These preliminary results indicate that the oligosaccharide component of vitellogenin in Xenopus laevis is a "complex" type of carbohydrate unit which is linked via an N-glycosidic bond between an asparagine residue and N-acetylglucosamine . With respect to the subcellular localization of glycoprotein assembly in Xenopus liver, there is a significant departure from currently accepted models of glycoprotein synthesis.

Med J Aust, 1982 Jan 9, 1(1), 18 - 20
Persistent post-enteritis diarrhoea in childhood: a prospective analysis of clinical features, predisposing factors and sequelae; Halliday K et al.; To investigate the incidence, pathophysiology and clinic determinants of persistent diarrhoea (more than seven days) after childhood gastroenteritis, we prospectively evaluated 168 consecutive patients admitted to the Royal Children's Hospital, Brisbane, with gastroenteritis . Thirty-two children (19%) developed persistent diarrhoea; only two-thirds of them had an identifiable aetiological factor, including di- or monosaccharide intolerance (31%), persisting or suspected pathogen (22%) and cow's milk protein intolerance . Computer aided analysis of risk factors in the preceding enteritis showed this complication to be more frequent in young age groups (P less than 0.01) where the patient was less than 10th percentile for weight (P les than 0.02); in Aboriginals (P less than 0.01); where there was a history of previous diarrhoea (P less than 0.001), delayed hospital admission (P less than 0.001) and antibiotic/antidiarrhoeal usage (P less than 0.05); and where there was a bacterial pathogen (P less than 0.001) . Severity and outcome were variable with most cases requiring a defined formula diet . These findings provide some insight into the problem of persisting diarrhoea after gastroenteritis, aid identification of at risk patients, and suggest guidelines for management and prevention.

Biochemistry, 1982 Jan 5, 21(1), 171 - 7
Biosynthesis of cell surface sulfated glycoproteins by cultured vascular endothelial cells; Heifetz A et al.; Cultured vascular endothelial cells incorporate 35SO4 into a class of oligosaccharides which are N-glycosidically linked to cell-surface or extracellular proteins . This type of sulfated oligosaccharide was not synthesized by smooth muscle cell cultures and may represent sulfation of vascular tissue glycoproteins which are unique to endothelial cells . These endothelial cell 35S-labeled oligosaccharides are not released from the polypeptides under alkaline conditions that cleave O-glycosidically linked chains . The incorporation of both {3H}hexosamine and 35SO4 into these oligosaccharides is inhibited by tunicamycin, an antibiotic which inhibits protein N-glycosylation . 35S-Labeled oligosaccharides, isolated as glycopeptides, were resistant to a variety of chemical and enzymatic treatments which degraded vascular cell sulfated glycosaminoglycans but appear to contain terminal sialic acid residues . Endothelial cell sulfated oligosaccharide chains could also be distinguished from sulfated glycosaminoglycans by the apparent size and charge . Endothelial cells released or secreted 35S-labeled glycoproteins into the culture medium . These soluble 35S-labeled glycoproteins were partially purified by DEAE-cellulose chromatography and separated from the 35S-labeled proteoglycans, which are also released into the medium . The major 35S-labeled glycoproteins released from the cells had apparent molecular weights of 24 000--66 000 . The cell-associated 35S-labeled glycoproteins, released with ethylenediaminetetraacetate or extracted with 0.5% octyl glucoside, were partially purified on DEAE-cellulose and had apparent molecular weights of 45 000--250 000.

Int Urol Nephrol, 1982, 14(4), 381 - 6
Post-prostatectomy infection: to treat or not to treat?
Fourcade R.
A prospective study of bacteriuria in 100 prostatectomies is analysed . The author states that an antibiotic policy which treats only patients with fever, clinical discomfort, or isolated bacteriuria after the first postoperative month does not enhance morbidity, and lowers hospital costs.

Langenbecks Arch Chir, 1982, 358, 119 - 24
{Indication, technic and results using the external fixator in infected fractures and infected pseudarthrosis}; Klemm K; Infected pseudo-arthrosis is the dreaded combination of chronic osteomyelitis and instability at the fracture site . Treatment consists in radical removal of sequestered bone and alloplastic implants, temporary implantation of Septopal chains for high-dose local antibiotic therapy and re-osteosynthesis with external fixator . The external fixator of Raoul Hoffmann is preferred because of its unlimited versatility . A total of 131 patients were treated in accordance with the method described . In 90.1% of the cases bone consolidation was achieved, and in 89.3% chronic osteomyelitis subsided.

J Cell Biochem, 1982, 20(1), 71 - 80
Intracellular accumulation of a fluorescent derivative of paromomycin in human fibroblasts; Buchanan JH et al.; Human fetal lung fibroblasts grown in the presence of dansyl-paromomycin (DNS-Pm), a fluorescent derivative of the aminoglycoside antibiotic, paromomycin, probably accumulate DNS-Pm in the lysosomes . The intracellular concentration of DNS-Pm is proportional to the extracellular concentration and to the length of time cells are exposed to the compound . The accumulation of DNS-Pm by human fibroblasts continued to increase for several days, reaching a saturation after 7 days . The kinetic data are consistent with the establishment of a steady state in the cell between fluid-phase pinocytosis and exocytosis of DNS-Pm . About 80% of the intracellular DNS-Pm ws released in 24 hr when fresh medium without the analogue was added . The residual 20% remained within the cells, suggesting that it may be irreversibly bound to the lysosomes, endoplasmic reticulum, or ribosomes . The uptake of paromomycin by cells in culture may be a useful means to study error propagation during growth and lifespan of cells in vitro.

Folia Histochem Cytochem (Krakow), 1982, 20(3-4), 157 - 62
The effect of doxycycline upon alkaline phosphatase activity in rat kidney (quantitative study using the interferometric technique); Wisniewska IE et al.; The doxycycline effect on the activity of alkaline phosphatase in the brush border of the convoluted renal tubules in rat was examined, using the interferometric technique . On the basis of measurements taken, the antibiotic was shown to cause a statistically significant fall of the alkaline phosphatase activity and the enzyme activity was found to decrease with consecutive doses of the drug under investigation.

Ann Otolaryngol Chir Cervicofac, 1982, 99(12), 569 - 73
{Actinomycoses in ORL}; Soudant J et al.; Diagnosis in a suspected case of laryngeal pseudo-actinomycosis was confirmed by examinations conducted in the Pasteur Institute . This capricious and misleading affection is reviewed, its treatment requiring only simple but prolonged antibiotic therapy.

Ann Med Interne (Paris), 1982, 133(7), 490 - 4
{Bacterial endocarditis on a mitral prosthesis with negative blood cultures . Case evolving over a 3 year period in the absence of fever}; Acar J et al.; A 38 year-old man, operated upon two years previously for combined mitral and tricuspid valve disease of rheumatic origin, presented with signs of a severe biological inflammatory syndrome, and a mild proliferative glomerulonephritis (normal complement with exclusively mesangial deposits of IgM, Clq, and C3 on immunofluorescence), which developed slowly over a period of 3 years in the absence of any fever . Blood cultures were always negative, and prolonged antibiotic therapy on two occasions had no effect on the clinical or biological picture . Mitral prosthesis replacement was necessary 6 months after the onset of the affection, a second leakage 16 months later leading to rapidly fatal heart failure . Pathological examination confirmed the presence of an endocarditis at the zone of insertion of the prosthesis . The slow progression of the disorder in this case, and the absence of fever, emphasize diagnostic difficulties of certain cases of endocarditis, due to low virulence germs, that progress under cover of a generalized disease of renal expression . The value of renal biopsy, which provided almost specific indications in the present case, is also stressed.

Q J Med, 1982, 51(204), 445 - 60
Systemic inflammatory complications following jejuno-ileal bypass; Fagan EA et al.; The clinical and laboratory features of three patients with systemic inflammatory complications following jejuno-ileal bypass surgery for morbid obesity are described . The constellation of an asymmetrical polyarthritis, tenosynovitis, sterile skin pustules, mucous membrane ulceration and retinal vasculitis resembled Behcet's syndrome . Serum complement levels were normal and circulating immune complexes not regularly detected, although hypocomplementaemia, elevations in Clq and rheumatoid factor binding materials were noted prior to clinical relapse in one patient . Antibiotic therapy proved disappointing, whereas dapsone produced a sustained remission . Bacterial overgrowth was not invariably found which together with recurrence of symptoms following bypass reversal, suggest that bacteria may only be required to initiate, not perpetuate inflammatory complications.

Antibiotiki, 1982, 27(9), 655 - 8
{Effect of aromatic amino acids on levorin biosynthesis}; Aleksintseva OA et al.; Aromatic amino acids, such as tryptophan and phenylalanine inhibit biosynthesis of levorin, while tyrosine stimulates it . The studies with resting cells showed that the changes in the level of the antibiotic production in the presence of the above amino acids were connected with their effect on the process of levorin biosynthesis and not on the growth of the antibiotic-producing organism . The changes in the content of the bound p-aminoacetophenone in the mycelium of Str . levoris correlated with the level of the antibiotic production . The amount of free p-aminoacetophenone in the mycelium of Str . levoris increased in the presence of the aromatic amino acids . It is suggested that the increase in the synthesis of levorin in the medium with addition of tyrosine was connected with inhibition of prefenic acid synthetase . Tryptophan must have an inhibitory effect on antranylate synthetase . Its effect on levorin synthetase is also possible.

Antibiotiki, 1982, 27(7), 502 - 7
{Cytomorphological changes in a culture of Streptomyces rimosus, the producer of oxytetracycline, in the presence of different foam retardants}; Dmitrieva SV et al.; The data on the effect of chemical foam suppressors of various classes on the morphogenesis of 2 strains of Streptomyces rimosus are presented . Correlation between the age of the culture and its reaction to unfavourable conditions is confirmed . During the first 24 hours of the growth the culture is most sensitive to low aeration rates, addition of the foam suppressors, fat deficiency in the medium . Among the foam suppressors used propinol B-400 had the most significant effect on the cells: destruction of the cell coating, marked changes in the morphogenesis and nucleocytosis of the hyphae of the second generation responsible mainly for the antibiotic biosynthesis . A more active strain was more subject to the foam suppressor toxic effect.

Zentralbl Chir, 1982, 107(15), 913 - 33
{Frequency and causes of wound infection and pneumonia rate following various surgical operations}; Grundmann R et al.; 753 patients who underwent general surgery were prospectively analysed with respect to postoperative wound infection and the pulmonary infection rate . A clear distinction was made between the real infection rate and those infections that were not combined with other complications and were therefore called "isoated" infections . It could be demonstrated that operations concerned with colon and perforated viscera had an increased isolated wound sepsis rate, the gastric resection, however, could be counted as a clean operation . Furthermore, the would sepsis rate after colonic surgery was also very low in those cases where an adequate operative techique was used . The pulmonary infection rate showed the opposite behaviour, since patients with gastric resection were particularly endangered . The reasons for that are discussed and target groups for use of prophylactic antibiotic therapy are named.

Methods Find Exp Clin Pharmacol, 1982, 4(2), 121 - 3
Effect of tobramycin on serum pseudocholinesterase levels; Paradelis AG et al.; Tobramycin given in a single dose of 1 mg.Kg-1 intramuscularly, in healthy male volunteers, did not produce any significant change in serum pseudocholinesterase levels . The above antibiotic given in a single dose of 2 mg.Kg-1 intramuscularly produced a statistically significant increase (p less than 0.05) of serum pseudocholinesterase levels 2 and 4 hours after its administration . However, this increase is very small to have any clinical significance . For the anaesthesiologist, a decrease, rather than an increase, of the serum pseudocholinesterase level should be of clinical significance.

Eur J Drug Metab Pharmacokinet, 1982, 7(2), 123 - 30
Pharmacokinetics of doxycycline polyphosphate after oral multiple dosing in humans; Saux MC et al.; Nine healthy volunteers received oral multiple doses of doxycycline polyphosphate for 6 days . Three different dosage schedules were given and the time concentration data obtained was used to determine the best protocol for producing effective serum antibiotic levels during a complete period of treatment with the aid of a mathematical simulation programme . This protocol consisted of the administration of a 200 mg loading dose on the first day, followed by a 100 mg maintenance dose every twelve hours . Using this dosage schedule a steady state was obtained on the first day of treatment, 3 mg/l was the maximum serum level reached, and the lowest serum concentration was more than 1 mg/l which was assumed to be a therapeutically effective serum concentration.

Curr Med Res Opin, 1982, 8(1), 1 - 4
A double-blind study of cefaclor and amoxycillin in home and hospital-acquired infections; Harrower AD; Eighty-seven patients admitted to hospital for a variety of reasons and who had, or subsequently developed, an infection were treated with either cefaclor or amoxycillin, 150 mg 3-times daily, on a double-blind basis . Two patients were excluded from te final analysis as the infecting organisms would normally be resistant to both antibiotics . Forty (93%) patients treated with cefaclor and 40 (95.2%) treated with amoxycillin responded satisfactorily . Of the patients with a hospital-acquired infection, 93.3% of the cefaclor group and 94.3% of the amoxycillin group responded satisfactorily . The differences between the groups were not significant . A greater number of organisms were sensitive to cefaclor, confirming its broader spectrum of activity . It is concluded that cefaclor is a useful first-line antibiotic which could be particularly useful in hospital-acquired infections.

Ann Otolaryngol Chir Cervicofac, 1982, 99(1-2), 41 - 6
{Cellulitis of the neck due to anaerobic germs: report of 10 cases (author's transl)}; Gehanno P et al.; Cellulitis of the neck in 10 patients was found to be due to anaerobic germ infections of either dental or tonsillar origins or following surgery . The lesion was diffuse in 8 cases, unilateral in two, and associated with signs of severe toxic infection in 9 cases . Early clinical crepitation was detected in 4 patients . The extremely poor prognosis related to the onset of infective shock and pleuropulmonary and mediastind complications, treatment including intensive care and anti-anaerobic germ antibiotic therapy . The place of surgical treatment is discussed, operative intervention being necessary when there are signs of poor general tolerance, not only in the presence of gas gangrene, but also when a diffuse cellulitis exists without signs of crepitation or the presence of fluid.

An Esp Pediatr, 1982 Jan, 16(1), 28 - 34
{Neonatal osteoarthritis . Report on 24 cases (author's transl)}; Garcia Sanchez P et al.; Twenty four neonates affected of osteoarticular infection, treated on the Neonatal Unit throughout a four and a half year period are analyzed . In the majority of instances they represent a complication in the course of neonatal sepsis . In more than half of them there was a previous umbilical vessel catheterization . "Staphilococcus aureus" was the most frequent etiologic agent . Involvement of the hip was the location more often seen and of worse prognosis . Treatment besides of supportative measures, and specific antibiotic therapy, included posterior arthrotomy in the 13 cases of hip arthritis, and diagnostic puncture and/or arthrotomy in the rest of locations . There was no mortality, and only 20% of the patients exhibits long-term residual defects of variable degree.

Jpn J Physiol, 1982, 32(1), 25 - 33
Coil planet centrifugal and capillary tube centrifugal analysis of factors regulating erythrocyte osmotic fragility and deformability; Nagasawa T et al.; Hydrated and dehydrated red cell samples were prepared from normal human red cells using the antibiotic nystatin . Furthermore, a series of red cell samples exposed to elevated temperature (20-50 degrees C, 10 min) were prepared . The osmotic fragility and deformability of these red cells were then measured, using the coil planet centrifuge system and the capillary tube centrifugal technique, respectively . The osmotic fragility of nystatin-treated red cells decreased and the deformability increased as dehydration of red cells progressed and alternatively, hydrated cells showed increased osmotic fragility and reduced deformability . Red cells exposed to elevated temperatures up to 49 degrees C for 10 min had no changes in mean corpuscular volume or in red cell shape . Above 47 degrees C, however, spectrin extractability progressively decreased and osmotic fragility and deformability decreased . Results suggest that the osmotic fragility snd deformability of red cells are interrelated, and are controlled by the geometry of the cell, including the ratio of cell surface area to cell volume and the viscoelastic properties of the membrane.

Ann Acad Med Singapore, 1982 Jan, 11(1), 118 - 21
A case of Ludwig's angina following tooth extraction; Yeo JF et al.; Ludwig's angina developed in an adult Chinese male following a mandibular third molar extraction . Brawny and tender swellings of the floor of the mouth and neck, with the elevation of the tongue, were classically present . The management of this case was based on the current emphasis of early broad-spectrum and antibiotic therapy with the maintenance of an adequate airway . The role of dental infection in this condition was highlighted.

Clin Orthop, 1982 Jan-Feb, (162), 31 - 6
Intervertebral discitis in children and adolescents; Scoles PV et al.; In 29 children wih symptoms and signs as well as laboratory and radiographic findings consistent with intervertebral discitis, the syndrome appeared to be a manifestation of both infectious and noninfectious inflammatory processes . When systemic sepsis is present, antibiotic therapy is indicated . In the absence of fever and leukocytosis, plaster cast immobilization should suffice . Craig needle aspiration and/or open biopsy are not routinely required, but should be reserved for those patients who fail to respond to routine treatment in whom tuberculosis is suspected.

Biofizika, 1982 Jan-Feb, 27(1), 14 - 6
{Determination of the number of GC-pairs "recognized" by actinomycin D during binding with DNA}; Mikhailov MV et al.; Experimental studies are reported on the binding of actinomycin D to various synthetic and naturally occurring DNAs . The experimental data obtained agree with a model in which the antibiotic molecule carries only one GC-specific reaction center and covers 5 base pairs upon binding to DNA . Positive cooperative effects are observed for the binding of actinomycin to poly(dG-dC)-poly (dG-dC) duplex.

Arch Dis Child, 1982 Jan, 57(1), 73 - 4
Acute infective pericarditis in infancy; Stroobant J et al.; Infective pericarditis is rare; the characteristic presenting illness in 3 children, each aged under one year, is recorded . Early diagnosis is important since surgical drainage of the pericardium is often necessary in addition to antibiotic therapy . The clinical features may suggest pericarditis, but diagnosis is readily and reliably confirmed by echocardiography.

Brain Dev, 1982, 4(1), 71 - 2
Late elevation of CSF proteins in three cases of mumps meningoencephalitis; Statz A et al.; Three children suffered from mumps meningoencephalitis and pneumonia . The clinical course was uneventful . After 2 weeks antibiotic therapy for pneumonia a repeat lumbar puncture showed a massive increase of CSF protein levels . This phenomenon was transitory . It is explained by an obstruction in CSF pathway in the course of mumps meningoencephalitis.

Antibiotiki, 1982 Jan, 27(1), 57 - 61
{Acute toxicity of the N-acyl derivatives of carminomycin and rubomycin}; Shepelevtsev NG et al.; Synthesis of 2 new N-acyl derivatives of carminomycin and rubomycin (N-L-leucylcarminomycin and N-sarcolysylrubomycin) is described . Acute toxicity of the new and 4 known N-acyl derivatives: N-acetylcarminomycin, N,L-alanylcarminomycin, N-D-phenylalanylcarminomycin and N-D-phenylalanylrubomycin was studied on albino mice . It was shown that the N-acyl derivatives of carminomycin and rubomycin had lower acute toxicity than the initial drugs . When added to blood serum in vitro N-D-phenylalanylcarminomycin and N-D-phenylalanylrubomycin induced precipitation . The carminomycin derivatives containing the residues of L-leucine and L-alanine were less toxic than the initial antibiotic, still they had a markedly pronounced retarded toxicity.

Fed Proc, 1982 Jan, 41(1), 78 - 83
Intestinal calcium transport: pleiotropic effects mediated by vitamin D; Norman AW et al.; The primary biological response to vitamin D is an increase in intestinal calcium transport . Efforts to elucidate the molecular mechanism by which this increased transport occurs has revealed that vitamin D mediates pleiotropic effects that are most likely a result of both genomic and nongenomic mechanisms of action of vitamin D . The spectrum of intestinal responses to vitamin D must now include an alteration in the topography of intestinal epithelial cells' brush border membrane (BBM) . Initial indications of such an event were obtained with the polyene antibiotic filipin . Filipin induces active calcium transport in vitro in the small intestine of vitamin D-deficient chicks by specifically interacting with cholesterol and thereby altering membrane organization . Alterations in BBM topography in response to vitamin D were detected with the use of membrane-impermeable protein-labeling reagents and limited proteolysis . Administration of vitamin D to vitamin D-deficient chicks induces specific changes in accessibility of BBM proteins to labeling reagents . In addition, an alteration is induced in the rate of solubilization of BBM hydrolases during limited proteolysis . These vitamin D-mediated alterations in membrane topography offer new possibilities for regulation of intestinal calcium transport.

Am J Otol, 1982 Jan, 3(3), 260 - 5
Clinicopathologic studies in tympanosclerosis; Makishima K et al.; Light-and electron-microscopic studies of the tissue from middle ears diagnosed as having tympanosclerosis, adhesive otitis media, postinflammatory ossicular fixation, and chronic otitis media revealed more or less similar findings of inflammatory response and healing . The histopathologic findings of "whitish sclerotic masses," especially around the ossicular chains, were due to fibrosis of submucosal connective tissue with hyalinization and calcification and/or metaplasia of mucosal epithelium . Longstanding and repeated undrained suppurative or nonsuppurative effusions would promote progressively more dense and avascular fibrous adhesions in the tympanum . The extensive fibrous changes in the tympanum would be a consequence of inadequate antibiotic therapy for middle ear inflammation and effusion . A new diagnostic term of tympanomastoidfibrosis is proposed to explain these clinical and histopathologic conditions as a replacement for the terms tympanosclerosis, adhesive otitis media, inflammatory ossicular fixation, and so on.

Postgrad Med, 1982 Jan, 71(1), 114 - 23
Pneumonia in the elderly; Horton JM et al.; The organisms to which the elderly are most susceptible are different from those affecting younger pneumonia patients . Furthermore, the pathogenesis of the disease varies with age, partly because of an increased incidence of underlying disease in older persons and partly because of the effects of the aging process itself . Presenting symptoms of pneumonia may be more subtle in the elderly than in younger patients, and clinical findings may also vary . Elderly pneumonia patients should always be hospitalized and treated immediately and aggressively with parenteral antibiotics according to results of the Gram stain . Once the pathogen involved is identified, more specific antibiotic therapy is begun . If physicians understand the unique characteristics of pneumonia in the elderly and act accordingly, they should play an important part in decreasing the relatively high mortality from the disease in this age-group.

Arch Otolaryngol, 1982 Jan, 108(1), 30 - 3
Chronic osteomyelitis following mandibular fractures and its treatment; Giordano AM et al.; In a review of 350 patients with mandibular fractures between 1976 and 1978, eight cases of chronic mandibular osteomyelitis were found . Treatment in all cases consisted of intravenous antibiotics and debridement . In addition, in some cases a suction-irrigation system was used after debridement . From this study, the following can be stated: (1) Osteomyelitis following mandibular fractures is uncommon . (2) Once chronic osteomyelitis has developed, aggressive antibiotic and surgical treatment is needed . (3) The use of the suction-irrigation system after debridement is an effective adjunctive aid in treating osteomyelitis . Cosmesis is superior to that obtained with older techniques because wounds are closed primarily.

Cancer Treat Rep, 1982 Jan, 66(1), 73 - 6
Phase I study of L-alanosine using a daily x 3 schedule; Dosik GM et al.; L-Alanosine is an antitumor antibiotic that inhibits adenine synthesis . It showed significant activity in animal tumor systems . Using a daily x 3 dose schedule every 3 weeks, we performed a phase I study to determine toxicity in man . Doses of 8-375 mg/m2/day x 3 were administered to 49 patients in 117 courses . The dose-limiting toxic effect was mucositis . Vomiting, infrequent myelosuppression, fever, headache, malaise, and blood pressure changes were detected at higher dose levels . No antitumor activity was noted . Toxicity with this regimen is acceptable . A phase II study with doses of 250 mg/m2/day x 3 every 3 weeks is feasible.

Microbiologica, 1982 Jan, 5(1), 57 - 61
Transport mechanisms of 6-diazo-5-oxo-L-norleucine in Escherichia coli K-12; Williams MV; The diazo antibiotic 6 diazo-5-oxo-L-norleucine is transported into Escherichia coli using the general aromatic amino acid transport system and a specific phenylalanine transport system . Resistance to this antibiotic is the result of a decreased rate of transport of the antibiotic and also the result of a more rapid rate of efflux of the antibiotic from the cell.

J Gen Microbiol, 1982 Jan, 128 (Pt 1), 107 - 14
Genetic stability of differentiated functions in Streptomyces hygroscopicus in relation to conditions of continuous culture; Roth M et al.; The genetic stability of the capacity of an improved strain of Streptomyces hygroscopicus to produce the macrolide antibiotic turimycin was investigated during long-term continuous culture . Dilution rate, growth-limiting substrate and culture temperature were varied . Certain culture conditions resulted in the stable propagation of the inoculated turimycin-producing population . Other conditions led to segregation of the initial population . Turimycin non-producing phenotypes appeared, and in each case the simultaneous loss of ability to form aerial mycelium was observed . The non-differentiating clones were found to be stable, without any reversion to the parental phenotype, indicating that a loss of genetic information probably took place.

Gut, 1982 Jan, 23(1), 1 - 7
Treatment of hepatic encephalopathy with metronidazole; Morgan MH et al.; Neomycin, an antibiotic which is primarily active against the aerobic gut flora and hence reduces the endogenous production of ammonia, is a well-recognised form of treatment for acute or acute on chronic hepatic encephalopathy . This study suggests that metronidazole may be a useful alternative or even adjunctive treatment for such patients . Theoretical and practical justifications for the use of this drug are presented . The results of a week's prescription of each drug have been assessed by changes in clinical and biochemical criteria, including electroencephalograms and arterial ammonia sample . In the treatment of a series of 11 mildly or moderately, and seven severely affected, patients with histologically confirmed cirrhosis, metronidazole is shown to be as effective as neomycin.

Antibiotiki, 1982, 27(7), 493 - 5
{Role of p-aminobenzoic acid in levorin biosynthesis}; Aleksintseva OA et al.; The effect of p-aminobenzoic acid on the biosynthesis of levorin was studied . It was shown that in the presence of exogenic p-aminobenzoic acid the antibiotic activity increased by 11 per cent . The acid added was transformed into p-aminoacetophenone which was partially used for levorin synthesis and partially accumulated in the mycelium in a free state . In this case the synthesis of levorin was limited by the metabolites forming the macrolide ring . When the precursors of the macrolide ring and the aromatic group were simultaneously added to the medium, the content of free p-aminoacetophenone in the mycelium decreased while the antibiotic activity increased by 25 per cent.

Ann Genet, 1982, 25(3), 149 - 51
{X chromosome fragility and effects of trimethoprim}; Lejeune J et al.; Severe clinical regression was observed in a patient carrier of a fragile X after treatment trimethoprime . This prompted us to examine the effect of this antibiotic in lymphocyte cultures: a dose ranging from 13 mg/l to 53 mg/l increases considerably the frequency of the Xq27 gap in four fragile-X patients; a dose of 13 mg/l allows a normal growth, without appearance of the Xq27 gap, in 19 normal, non-carrier subjects; a dose of 82 mg/l totally inhibits cell division in 10 normal, non carrier subjects . The reversibility of the blockade was demonstrated, either by washing out the trimethoprime before the 50th hour of incubation or by adding 5-formyl-tetrahydrofolate (0.125 mg/l) . It is concluded that one of the steps of monocarbon metabolism is inhibited by trimethoprime . This antibiotic, which must be avoided when treating patients carrier of the fragile X can be utilized in vitro for cytogenetic investigations.

Am J Ophthalmol, 1982 Jan, 93(1), 39 - 41
Endophthalmitis after strabismus surgery; Salamon SM et al.; We treated two cases of endophthalmitis caused by strabismus surgery . In one patient, a scleral perforation was recognized during surgery and treated with cryopexy . In the other, a scleral perforation was suspected but never confirmed . Despite intensive antibiotic and corticosteroid therapy, visual acuity decreased to light perception in Case 1 and to counting fingers in Case 2 . The second eye was enucleated eight years later after it had become blind and painful.

Rev Stomatol Chir Maxillofac, 1982, 83(5), 279 - 82
{Sequestral osteitis with fracture of the mandibular angle occurring secondarily to the extraction of a wisdom tooth . Apropos of a case}; Cantaloube D et al.; The authors report on a case of sequestrated osteitis complicated by a fracture of the angle of the mandible, following the avulsion of a wisdom tooth in a 20 year old man . The treatment consisted of an intermaxillary fixation of the mandibular arche lasting 40 days accompanied by wide-spectrum antibiotic therapy for 15 days, until such time as the ESR and blood count values returned to normal . In three months resorbtion of the sequestrated necrotic bone and disappearance of the osteitic cavity was noted, all of which was indicative of a satisfactory result . From the aetiological point of view it was possible to confirm by way of a routine X-ray taken 5 days after the extraction that the lesions had developed of their own accord, thus eliminating surgery and trauma as causes . The problem of what causes maxillary osteitis remains, and in particular, the role played by local anaesthetics containing adrenaline.

Cancer Chemother Pharmacol, 1982, 8(1), 41 - 6
Plasma kinetics of aclacinomycin A and its major metabolites in man; Egorin MJ et al.; The plasma pharmacokinetics of the antineoplastic anthracycline antibiotic aclacinomycin A (Acm) and its metabolites were studied in 12 patients treated with 60-120 mg/m2 during a phase I clinical trial . Total plasma drug fluorescence initially declined very rapidly, but from 2 to 24 h after injection, fluorescence rose progressively to intensities greater than those measured 1 min after Acm injection . Plasma total drug fluorescence slowly declined from 24 to 72 hours after Acm administration . These events reflected the rapid disappearance of Acm and the subsequent appearance of two highly fluorescent metabolites . One metabolite co-chromatographed with and had a fluorescence spectrum identical to known metabolite F1 (bisanhydroaklavinone) . The other metabolite did not co-chromatograph with any previously described Acm metabolite . This metabolite had a fluorescence spectrum unlike any previously described Acm metabolite and was not altered by treatment for 60 min with 0.2 N HCl at 100 degrees C or by treatment for 24 h at 37 degrees C with bacterial beta-glucuronidase or limpet aryl sulfatase.

Boll Ist Sieroter Milan, 1982, 61(5), 437 - 40
{Treatment with levamisole in a case of deficiency of the neutrophil granulocyte function associated with an increase in plasma IgA and recurrent dermal abscess infections}; Pigatto PD et al.; The authors describe a case of recurrent dermal abscess infections resistant to usual antibiotic therapy and demonstrating a failing of the activity of the neutrophils and a remarkable increase of plasmatic IgA . The treatment with Levamisole regularized the laboratory data and, as a result, determined a consequent important improvement of the patient.

Acta Chir Scand, 1982, 148(2), 205 - 7
Septic false aneurysms . Report of three cases; Dryjski M et al.; Three cases of septic false aneurysms are reported . They appeared as palpable pulsating masses shortly after severe septic episodes and were diagnosed by angiography . Two aneurysms were located in the common iliac artery and one in the superficial femoral artery . Operation was performed under antibiotic coverage and included ligation of the artery and excision of the aneurysm . Immediate reconstruction was performed in one case, in the two remaining, such reconstruction was abstained from since intraoperative ankle pressures were judged adequate . In one case reconstruction was performed later to relieve claudication . All patients survived with functioning extremities.

Symp Soc Exp Biol, 1982, 35, 381 - 97
Surface properties of the euglenoid flagellum; Bouck GB et al.; New structural details of the Euglena flagellum have led to a modified interpretation of the arrangement of the mastigoneme sheath and its internal attachment . A paraaxial ribbon is described which is located between the flagellar membrane and the axonemal microtubules . This fine ribbon apparently binds mastigoneme units and in turn is bonded to three peripheral microtubule doublets in a position approximately opposite that of the paraflagellar rod . The latter structure seems to anchor one half of the flagellar sheath while the paraaxial ribbon anchors the other one half of the flagellar sheath . Immunological labelling of Euglena mastigonemes has demonstrated that mastigonemes are present in the reservoir as well as on the flagellar surface if monovalent Fab' is used on deflagellated cells . Pulse labelling with anti-mastigoneme Fab' in regenerating cells showed the initial reservoir label was lost and indicated that the labelled mastigonemes were transferred to the flagellum . The reservoir is thus demonstrated to contain a surface pool for flagellar mastigonemes . Flagellar regeneration is partially inhibited irreversibly by the glycoprotein synthesis inhibitor tunicamycin . Experiments with cycloheximide and tunicamycin suggest each antibiotic affects different moieties and that some glycoprotein(s) is limiting to flagellar growth in Euglena . It is postulated that mastigonemes are possible candidates for that rate-limiting component.

Mol Gen Genet, 1982, 187(1), 148 - 56
Conjugation-deficient mutants of Escherichia coli distinguish classes of functions of the outer membrane OmpA protein; Manoil C et al.; Sixty-two E . coli mutants, selected as being deficient as recipients in F factor conjugation, are altered either in the amount or function of the outer membrane OmpA protein or in lipopolysaccharide structure . These two components may function together in conjugation, since the residual conjugation activity of a mutant lacking OmpA protein was unaffected by the additional presence of a lipopolysaccharide defect . Sixty of the strains carried mutations mapping to ompA, and these could be divided into classes depending on the amount of OmpA protein in their membranes . Representatives of these classes of mutant alleles failed to complement in diploids, indicating that they all affect the ompA structural gene and nearby sequences needed for its expression . The properties of these classes distinguish three groups of OmpA protein functions: 1) the structural function in the outer membrane in providing resistance to chelating agents and the hydrophobic antibiotic novobiocin, 2) the receptor functions in phage TuII and K3 infection, and 3) the functions of binding cells together during conjugation, facilitating the uptake of receptor-bound colicin K or L, and allowing phage Ox2 to infect . Different cellular amounts or sites in OmpA protein are thus required for these three groups of functions.

Antibiotiki, 1982, 27(9), 678 - 81
{Action of tetracycline and rifampicin on Rickettsia prowazekii and Rickettsia sibirica}; Kashliaev TK et al.; The effect of tetracycline and rifampicin on R . prowazekii, strain Breinl and R . sibirica, strain X1 was studied in the experiments with chick embryos exposed to the antibiotic mixture with the infection material . It was shown that tetracycline in doses of 0.1 and 1 mg/embryo had the rickettsiostatic and rickettsiocidic effects respectively on R . sibirica . Rifampicin had only the rickettsiostatic effect in a dose of 0.1 mg/embryo and no rickettsiocidic effect even in a dose of 2 mg/embryo . Higher doses were toxic for 100 per cent of the embryos . The rickettsiostatic and rickettsiocidic effects of tetracycline on R . prowazekii were evident in doses of 0.05 and 0.1 mg/embryo, respectively . Rifampicin in a dose of 0.05 mg/embryo had both the rickettsiostatic and the rickettsiocidic effects on R . prowazekii . Therefore, rifampicin was more active with respect to R . prowazekii and tetracycline was more active with respect to R . sibirica . In addition, R . sibirica was more resistant to both tetracycline and rifampicin as compared to R . prowazekii.

Adv Enzyme Regul, 1982, 20, 233 - 44
Hypoxic cell specific chemotherapeutic agents; Sartorelli AC; Cellular subpopulations of solid tumors can be divided into compartments based upon their degree of oxygenation and their rate of proliferation . Based upon these considerations, combinations of drugs and other therapeutic modalities can be devised with the potential to eradicate the physiologically heterogeneous populations of tumor stem cells present in solid neoplasms . Selection of combinations of drugs or other treatment modalities based upon these concepts makes the inclusion of an agent or agents with the capacity to eliminate hypoxic stem cells mandatory to achieve cure . The bioreductive alkylating agent, mitomycin C, would appear to be the most efficacious agent presently available for this purpose, and it is proposed that this antibiotic be considered as an addition to therapeutic regimens designed for the treatment of solid tumors . To employ this agent in a manner that minimizes its toxicity to normal cellular elements, it is necessary to consider that the mechanism by which mitomycin C exerts its cytotoxicity to oxygenated cells is different from that by which it kills hypoxic cells . Mitomycin C can undergo 1-electron reduction in the presence of oxygen (46, 47) . Subsequent reoxidation of the antibiotic by molecular oxygen can lead to the generation of superoxide radical and other toxic oxygen-containing species, such as hydrogen peroxide and hydroxyl radical . Such cyclic reduction and oxidation of mitomycin C by oxygenated cells may result in the generation of levels of toxic oxygen species that surpass the detoxification capacity of cellular scavenging systems, and thereby may be responsible for the toxicity of this antibiotic to aerated cells in tumors and normal tissues, whereas the cytotoxicity of mitomycin C to hypoxic cells may involve the 2-electron reduction and generation of the reactive quinone methide species shown in Figure 3 . These considerations dictate that to maximize the differential toxicity of an agent such as mitomycin C to hypoxic cells requires that it be given in relatively low doses, perhaps by constant infusion to maximize its potential for diffusion into neoplastic masses to reach hypoxic stem cells.

EMBO J, 1982, 1(10), 1199 - 205
The elongation factor Tu.kirromycin complex has two binding sites for tRNA molecules; van Noort JM et al.; The interaction of the polypeptide chain elongation factor Tu (EF-Tu) with the antibiotic kirromycin and tRNA has been studied by measuring the extent of protein modification with N-tosyl-L-phenylalanine chloromethylketone (TPCK) and N-ethylmaleimide (NEM) . Kirromycin protects both EF-Tu.GDP and EF-Tu.GTP against modification with TPCK . Binding of aminoacyl-tRNA added at increasing concentrations to a solution of 40 microM EF-Tu.GDP.kirromycin complex re-exposes the TPCK target site on the protein . However, when the aminoacyl-tRNA concentration is raised beyond 20 microM, TPCK labeling drops again and is blocked completely at approximately 300 microM aminoacyl-tRNA . By contrast, addition of uncharged tRNA or N- acetylaminoacyl -tRNA enhances TPCK labeling of the protein over the entire tRNA concentration range studied . These data strongly suggest that kirromycin induces in EF-Tu.GDP an additional tRNA binding site that can bind uncharged tRNA, aminoacyl-tRNA, and N- acetylaminoacyl -tRNA . Support for this assumption is provided by measuring the modification of EF-Tu.GDP with the sulfhydryl reagent NEM . Moreover, NEM modification also indicates an additional tRNA binding site on EF-Tu.GTP.kirromycin, which could not be detected with TPCK . Mapping of the tryptic peptides of EF-Tu.GDP labeled with {14C}TPCK revealed only one target site for this agent, i.e., cysteine-81 . Modification occurred at the same site in the presence and in the absence of kirromycin and uncharged tRNA.(ABSTRACT TRUNCATED AT 250 WORDS)

Circ Shock, 1982, 9(5), 543 - 53
Current management of the septic shock patient: experimental basis for treatment; Hinshaw LB et al.; Experimental research has shown that following the intravenous infusion of animals with bacteria or endotoxin a myriad of adverse vascular events occur resulting in deficient organ perfusion and cell death . The primary goals of therapy for sepsis and septic shock, therefore, should include elimination of the source of infection and/or infectious agents and prevention or reversal of adverse vascular events . The following review describes the evolution of an effective therapy for shock consisting of steroid in combination with antibiotic and discusses its relevance and application for humans in severe sepsis or septic shock.

J Int Med Res, 1982, 10(5), 333 - 40
The weeping ear: clinical re-evaluation of treatment; Gyde MC et al.; This study was designed to compare the efficacy and safety of gentamicin otic solution versus colistin-neomycin-hydrocortisone otic suspension in the treatment of otorrhoea due to infection . Fifty-five patients (mean age 36.6 +/- 22.1 years) with sixty infected ears with otorrhoea complicating otitis externa, recurrent otitis media with tympanic membrane perforation, or infected mastoid cavities and post-operative tympanoplasties, were treated for 14 days with either an aqueous solution of gentamicin 0.3% or an aqueous suspension of colistin 0.3%, neomycin 0.33% and hydrocortisone 1.0% . The two possible treatments were assigned randomly and the results were assessed double-blind using usual ordinal scales for monitoring the severity of symptoms . Both otic preparations were found to be equally safe in the treatment of otorrhoea due to infection . No side-effects were observed and hearing status was either unchanged or improved . The antibiotic-steroid combination appeared to be more effective in relieving inflammation in a shorter period of time while gentamicin was observed to be more effective in eradicating the infecting organisms.

Adv Shock Res, 1982, 7, 13 - 23
Survival characteristics during septic shock in 39 baboons; Wilson MF et al.; In septic shock nonsurvival is characterized by failure of multiple organ systems . The design of therapeutic measures to increase survival would be enhanced if critical responses could be identified early . Escherichia coli LD100 was given to 39 baboons by IV infusion over two hours followed by different therapy regimens in 31 {2--4} . There were 18 permanent survivors (seven days or more), all receiving antibiotic/steroid combination therapy . Responses of survivors and nonsurvivors were measured and compared during the first 12 hours from onset of infusion . Changes in blood pressure and acid-base parameters were not significantly different between groups . Five responses indicative of permanent survival were lower heart rates, less elevation of blood urea nitrogen, normal blood glucose at eight hours, hyperglycemia with normal insulin at 12 hours, and lower plasma lactate concentrations beginning at four hours.

Oncology, 1982, 39(2), 72 - 77
Mithramycin impairs the release of 45Ca from bone induced by prostaglandin E2 or multiple myeloma sera . Implications for a novel means of local tumor control; Anderson KM et al.; Some tumors release factors able to activate host osteoclasts . Mithramycin at sub-tumoricidal doses inhibits the release of calcium mediated by osteoclasts . If invasion of bone by a cancer requires activation of these cells, their intermittent "blockade' might impede the development of metastases to bone or their local extension . Fetal rat bones prelabelled with 45Ca were cultured in the presence of 10(-7) M prostaglandin E2, sera from normal individuals, or from patients with multiple myeloma . Additional samples preincubated for 3 h with 1 microgram/ml of mithramycin, were washed before culture . Compared with controls, prostaglandin E2 stimulated the release of 45Ca by 28% (5 experiments) and mithramycin inhibited release by 15% (3 experiments) . Preexposure to this cytotoxic antibiotic before culture with PGE2 reduced the augmented release . Sera from 4 patients with multiple myeloma were incubated with 45Ca-labelled bones, some pretreated with mithramycin . An additional 29% release of 45Ca (4 experiments) was prevented by mithramycin . These results are consistent with the hypothesis that augmented release of 45Ca due to stimulatory factors such as prostagladins or factors in sera from patients with multiple myeloma can be partially inhibited by pretreatment with mithramycin . Possibly, intermittent blockade of host osteoclasts can impair formation of metastases to bone by cancers dependent upon their activation for this event, or reduce the extent of local invasion by established metastases . Modifying the behavior of a cancer by altering the host-response to factors which it releases represents a potential alternative to cytotoxic chemotherapy.

EMBO J, 1982, 1(6), 755 - 9
Phenotypic reversion of an IS1-mediated deletion mutation: a combined role for point mutations and deletions in transposon evolution; Lida S et al.; We have physically characterised a deletion mutant of the R plasmid R100 which has lost all of the antibiotic resistances, including chloramphenicol resistance (Cmr), coded by its IS1-flanked r-determinant . The deletion was mediated by one of the flanking IS1 elements and terminates within the carboxyl terminus of the Cmr gene . DNA sequence analysis showed that the mutated gene would produce a protein 20 amino acids longer than the wild-type due to fusion with an open reading frame in the IS element . Surprisingly for a deletion mutation, rare, spontaneous Cmr revertants could be recovered . Two of the four revertants studied had frame shifts due to the insertion of a single AT base pair at the same position; the revertants would code for a protein five amino acids shorter than the wild-type . The other two revertants had acquired duplications of the 34-bp inverted terminal repeat sequences of the IS1 element and would direct the synthesis of a protein six amino acids longer than the wild-type . The reverted Cmr markers were still capable of transposition . These observations suggest a role for point mutations and small DNA rearrangements in the formation of new gene organisations produced by mobile genetic elements.

J Mol Appl Genet, 1982, 1(6), 513 - 25
A fragment of Dictyostelium discoideum genomic DNA that complements the URA1 mutation of Saccharomyces cerivisiae; Jacquet M et al.; A strain of Saccharomyces cerivisiae carrying a mutation in the URA1 gene was transformed with fragments of Dictyostelium DNA inserted into a plasmid capable of replication in E . coli or yeast . Rare prototrophic colonies were recovered that all contained the parent plasmid and an insert of Dictyostelium DNA . Resistance to the antibiotic G418, a function coded by the same plasmid, was also expressed in the prototrophs . Plasmids recovered from the prototrophic yeast could be used to transform E . coli . The E . coli transformants harbored plasmids capable of transforming yeast URA1 mutants to prototrophy . No complementation of the E . coli pyrD mutation, which corresponds to URA1, occurred . Southern blot analysis revealed that the insert of Dictyostelium DNA contained a unique sequence of 1700 base pairs and a repetitive one of 1000 base pairs . Subcloning experiments showed that only the unique sequence was required for complementation, which is independent of the orientation of the Dictyostelium sequence in the plasmid . The repetitive fragment was not linked to the unique sequence in the genome and was probably an artifact of the ligation procedure . The unique sequence hybridized to a Dictyostelium polyA+ RNA species of 1200-1300 bases.

Clin Ther, 1982, 5 Suppl A, 67 - 73
Comparative efficacy of cefotaxime and cefazolin as prophylaxis against infections following elective hysterectomy; Wideman GL et al.; The safety and efficacy of cefotaxime and cefazolin as prophylaxis against posthysterectomy infections were compared in a prospective, randomized study . A total of 118 women undergoing elective vaginal or abdominal hysterectomy were randomly assigned to receive either (1) cefotaxime perioperatively, (2) cefotaxime perioperatively and 24 hours postoperatively, or (3) cefazolin perioperatively and 24 hours postoperatively . In all regimens, the initial antibiotic dose was given intramuscularly and subsequent doses were given intravenously . No postoperative pelvic or wound infections developed in patients in any of the three study groups during the hospital stay or in the 30-day follow-up period . No side effects or changes in laboratory test values attributable to the antibiotics were noted . The results of the study indicate that (1) standard one-day regimens of cefotaxime and cefazolin are equally safe and effective as prophylaxis against posthysterectomy infections, and (2) a brief, three-dose perioperative course of cefotaxime is as effective as a standard one-day regimen of either cefotaxime or cefazolin and has the advantages of reduced cost and greater convenience.

Clin Ther, 1982, 5 Suppl A, 10 - 8
Cefotaxime treatment in patients with osteomyelitis and septic arthritis: a multicenter study; Mader JT et al.; The effectiveness of parenteral cefotaxime in the treatment of adults with acute septic arthritis or acute or chronic osteomyelitis was evaluated in a multicenter trial . The drug was given to 47 patients admitted to the University of Texas Medical Branch Hospitals or Hahnemann Medical College and Hospital (UT-H study) and to 40 patients in other medical centers using an identical protocol . In the UT-H study, cefotaxime was effective in 15 of 16 patients (94%) with acute osteomyelitis, in 24 of 27 patients (89%) with chronic osteomyelitis, and in four of four patients (100%) with acute septic arthritis . In the multicenter study, the success rates were as follows: acute osteomyelitis, six of six (100%); chronic osteomyelitis, 14 of 19 (74%); and septic arthritis, 12 of 15 (80%) . The antibiotic was well tolerated in most patients . The most serious side effect was significant neutropenia, which occurred in three patients . Cefotaxime appears to be a clinically useful, broad-spectrum antibiotic for bone and joint infections.

J Neurosci, 1982 Jan, 2(1), 1 - 10
Extracellular current flow and the site of transduction by vertebrate hair cells; Hudspeth AJ; The transduction process of a vertebrate hair cell commences with the application of mechanical stimuli to the hair bundle, a cluster microvillous stereocilia and single axonemal kinocilium . In an effort to determine where within the hair bundle transduction occurs, I have measured extracellular potentials around the hair bundles of mechanically stimulated hair cells from the bullfrog's sacculus . Stimulus-dependent signals up to 17 microV in peak-to-peak amplitude have been found . These appear to be due to the flow of transduction current on the basis of their amplitude, phase, dependence on stimulus size and orientation, proportionality to membrane potential, and sensitivity to an ototoxic antibiotic . The responses are consistently larger near the top of the hair bundle than at its base, suggesting that the transduction apparatus lies at or near the distal ends of the stereocilia.

Vet Med Nauki, 1982, 19(9), 66 - 72
{Pharmacological and toxicological studies of Amopen powder in lambs}; Lashev L; The oral administration of amopen pulvis (containing 5 per cent amoxicillin trihydrate) led to the rapid resorption and elimination of amoxicillin as a constituent of the drug formula . Resorption was found to depend on the development of the forestomach . In weaned lambs it was twice as low than in sucking lambs . The antibiotic was retained in bacteriostatic concentrations up to the twelfth hour in sucking lambs and up to the tenth hour in weaned lambs following the application of 0.5, resp., 0.7 g/kg mass, corresponding to the rates of 0.015 and 0.025 g/kg mass so far as amoxicillin trihydrate was concerned . Fivefold higher doses applied to lambs did not lead to essential changes in the general state, hemoglobin value, and blood picture.

Acta Biomed Ateneo Parmense, 1982, 53(6), 435 - 43
{Traumatic perforations of the esophagus}; Foggi E et al.; The Authors describe 6 patients with esophageal jatrogenic of foreign body perforation treatment during the last 5 years . The early recognition and immediate direct suture of the lesion proved a simple and efficient treatment . At the contrary a delayed diagnosis represent the cause of morbidity and mortality (one case on the six described) being impossible a direct suture of the lesion as consequence of local and general infective complication leading to very long postoperative causes with possible iterative surgery . The use of T.P.N . and of antibiotic therapy gascromatografich testing guides for anaerobic infection provide today a much improved prognosis for these patients.

Vet Med Nauki, 1982, 19(8), 65 - 72
{Amoxicillin resorption and retention in calves and pigs treated with Amopen powder}; Lashev L; Determined were the serum concentrations of amoxicillin at the single and repeated oral administration to calves and pigs of the drug formula amopen-powder, containing 5 per cent amoxicillin tryhydrate . It was found that the resorption of the antibiotic was rapidly setting in, and there were high concentrations in the blood serum of the treated animals, in pigs both the resorption and the elimination of amoxicillin occurring at a higher rate . In calves with developed forestomach the antibiotic was resorbed twice slower than in sucking calves . In pigs the increase in feed with which the drug was offered resulted in its weaker resorption in the digestive tract.

Infection, 1982, 10 Suppl 3, S209 - 12
{Mezlocillin and oxacillin concentrations in the bile of the choledochus}; Brandstatter G et al.; The purpose of this study was to determine the antibiotic concentrations in serum and bile one and two hours after the completion of a simultaneous short-term infusion of 4 g mezlocillin and 2 g oxacillin . Seven patients were studied . Bile was withdrawn from the bile duct by means of a Teflon catheter . The mean serum concentrations of mezlocillin were 130.4 mg/l and 60.8 mg/l one and two hours after the end of the infusion, respectively . The mean serum concentrations of oxacillin determined at the same times were 57.9 mg/l and 18.9 mg/l, respectively . The mean biliary levels of mezlocillin were 3215.6 mg/l and 2483.1 mg/l one and two hours after the end of the infusion, respectively . The corresponding mean biliary values for oxacillin were 497.3 mg/l and 205.5 mg/l.

Acta Biol Med Ger, 1982, 41(11), 1087 - 90
The effect of Rb+, Cs+, and T1+ on the gramicidin A-induced conductance changes of the skeletal muscle cell membrane; Caffier G et al.; The channel-forming antibiotic gramicidin A increases the K+ conductance of frog skeletal muscle fibres in isotonic K2SO4 solution . The conductance of the gramicidin channel is not affected by Rb+ or Cs+, but is reduced by T1+ . In contrast, the conductance of the normal K+ channel is decreased by Rb+ and Cs+ but is nearly unaffected by 5 and 10 mM T1+ . The results suggest differences in the cation permeation through the gramicidin and the K+ channel of the muscle cell membrane.

Dtsch Z Verdau Stoffwechselkr, 1982, 42(5), 217 - 21
{Whipple's disease}; Weise L et al.; With regard to three cases, one of them relapsing after four years, a short survey on Whipples's disease is given . The 3 male patients of medium age suffered from malabsorption and foregoing arthralgia . These symptoms are typical . In most cases first of all chronic infectious or neoplastic diseases are taken into consideration . The finding of PAS-positive macrophages in biopsies of the duodenal mucosa is key to the diagnosis, allowing the successful antibiotic therapy, with preference to oxytetracyline.

Antibiotiki, 1982, 27(9), 646 - 9
{Acid-base properties of gramicidin C}; Komarov EV et al.; The acid and basic properties of gramicidin S, a polypeptide antibiotic were studied . Calculation of the protonization constants with the Schwarzenbach method showed that the capacity of the antibiotic amino groups for protonization depended on both the solvent nature and the gramicidin S concentration . No such phenomena were observed in the study on the acid and basic properties of N,N -dimethyldiaminogramicidin . This confirmed the possible effect of the association of the gramicidin S molecules on the protolytic properties of the antibiotic.

Int J Biochem, 1982, 14(9), 805 - 9
Nilemycin, an intercalating agent for deoxyribonucleic acid; Shimi IR et al.; 1 . Nilemycin (NM) is found to exert an inhibitory effect on the mouse tumor Sarcoma 180 near toxic doses but not with Leukemia 1210 . 2 . In Yoshida rat sarcoma cells NM inhibits cellular de novo nucleic acid synthesis and protein to a much lesser extent . 3 . More than 50% inhibition by NM to de novo synthesis of RNA, in a system using calf thymus DNA as a template, could be observed . 4 . Suitable levels of NM reduce the S values of DNA . 5 . The antibiotic induced metachromatic changes in the u.v . spectrum of DNA solutions . 6 . NM markedly inhibited the polynucleotide ligase repairing action on DNase-1-nicked DNA . 7 . It is presumed that NM intercalates nicked DNA into such a configuration that the reactive sites of the polynucleotides are inaccessible to the ligase activities.

Int Arch Allergy Appl Immunol, 1982, 69(1), 86 - 8
Some characteristics of histamine secretion from mast cells treated with ionomycin; Truneh A et al.; The ionophorous antibiotic ionomycin released histamine from rat peritoneal mast cells in both the presence and absence of added calcium ions . The response under the latter conditions was potentiated by brief pretreatment of the cells with chelating agents . The interaction between the ionophore and exogenous calcium was complex . Supramaximal concentrations of calcium potentiated the release induced by low levels of ionomycin but markedly inhibited the secretion evoked by larger amounts of the compound . Dispersed mesenteric mast cells of the rat and guinea pig also responded to ionomycin but were less reactive than the peritoneal cells.

J Foot Surg, 1982 Summer, 21(2), 108 - 10
Verrucae plantaris--effective treatment with bleomycin: review of the literature and case presentations; Koenig RD et al.; Single and multiple verrucous plantaris lesions are well known for their resistance to conservative methods of treatment . In an effort to destroy verrucous growth, the authors have attempted to alter the genetic structure of these obstinate, benign warty lesions by using the antibiotic, bleomycin sulfate . This study provides a review of the medical literature and presents the intralesional injection technique of 0.1% bleomycin into the wart tissue itself . The impressive and significant success rate for complete resolution of verrucous lesions without subsequent scarring has shown this approach to be an effective treatment for plantar warts.

Folia Microbiol (Praha), 1982, 27(2), 81 - 6
The effect of rifampicin on Mycobacterium smegmatis; Majtan V et al.; Rifampicin was found to inhibit the growth and incorporation of 14C-adenine, 14C-leucine and 14C-glycine in exponentially growing cells of M . smegmatic cultivated in Merrill's synthetic medium . Increasing concentrations of the antibiotic inhibited respiration in resting cells, in the presence of glucose or 2-oxoglutarate as substrates in particular . In addition to the well-known interference of rifampicin with the biosynthesis of RNA, the effect on the energy metabolism should also be considered.

Gastroenterology, 1982 Jan, 82(1), 46 - 50
A submucosal variant of Whipple's disease; Kuhajda FP et al.; We describe an unusual case of Whipple's disease, in a patient previously treated for tuberculosis, in which involvement of the small intestine was restricted to the submucosa . This is of diagnostic importance since the presence of Whipple's disease cannot be established by jejunal biopsy in such cases unless the submucosa is adequately sampled . It is possible that this unusual distribution of intestinal infection is related to the effects of e antibiotic therapy . Retrospective study of the patient's serum cholesterol, carotene, and albumin suggests that malabsorption may occur in Whipple's disease despite the absence of infection in the mucosa.

J Membr Biol, 1982, 64(1-2), 67 - 76
An ATP-driven proton pump in brush-border membranes from rat renal cortex; Kinne-Saffran E et al.; The rate of ATP hydrolysis in ATP-preloaded plasma membrane vesicles derived from the luminal membrane of renal cortical tubules, and the rate of H+ secretion out of the same vesicles were investigated . Both were inhibited at low temperature, by the action of filipin, an antibiotic that complexes with cholesterol in plasma membranes, and by the action of blockers of mitochondrial Fo hydrogen channels, dicyclohexylcarbodiimide and Dio-9 . Valinomycin in the presence of K+ showed a stimulatory effect, the protonophor carbonyl-cyanid-p-trifluormethoxy-phenylhydrazone stimulated the intravesicular ATP hydrolysis and apparently abolished acidification of the extravesicular medium . Lowering of the pH of the extravesicular medium retarded ATP hydrolysis, while readjustment of extra- and intravesicular pH accelerated ATP hydrolysis again . These findings strongly support the assumption that an ATP-driven proton pump is located in the luminal membrane of renal cortical tubules.

Rev Argent Microbiol, 1982, 14(3), 171 - 6
{Inhibition of the production of infectious particles in cells infected with Junín virus in the presence of tunicamycin}; Daelli MG et al.; The antibiotic tunicamycin, an inhibitor of glycoprotein synthesis, suppressed Junin virus multiplication in Vero cells . No infectious virus was formed if tunicamycin was added, at a concentration of 1 microgram/ml, immediately after virus adsorption and remained up to the end of the replicative cycle . Tunicamycin added at 24,48 or 72 hours p.i . immediately stopped virus synthesis . The effect was irreversible . Virus grown in the presence or absence of tunicamycin and labelled with 3H-uridine was purified and layered on a (20-60%) sucrose gradient . The radioactive profile of both gradients was coincident . The total number of cpm associated to the peak gradient of virus grown with tunicamycin represented 70% of the cpm from control virus . Since viral infectivity was 99.4% inhibited in the presence of TM it can be assumed that most of the radioactive particles formed are not infectious . Therefore, in the presence of tunicamycin Junin virus buds normally . From these results we can conclude that carbohydrates are important for viral infectivity but play no role in the transport of viral proteins through cellular membranes.

Nucleic Acids Res, 1981 Dec 21, 9(24), 6889 - 906
Rifampicin inhibition of RNA synthesis by destabilisation of DNA-RNA polymerase-oligonucleotide-complexes; Schulz W et al.; Although the antibiotic rifampicin inhibits the transcription of poly{d(A-T)} by E.coli RNA polymerase, a series of short oligonucleotides is produced . It is claimed that the overall inhibition of RNA synthesis by rifampicin is caused by a destabilising effect on the binding of the intermediate oligonucleotides to the active enzyme-DNA complex . Rifampicin itself can only interact specifically with RNA polymerase if the enzyme is free or in a binary complex with DNA . However, the enzyme is not susceptible in a ternary complex, even if the "RNA" is as short as a trinucleotide.

Biochim Biophys Acta, 1981 Dec 7, 649(2), 336 - 42
Fluorescent alamethicin fragments . A study of membrane activity and aqueous phase aggregation; Mathew MK et al.; The linear polypeptide antibiotic alamethicin is known to form channels in artificial lipid membranes . Synthetic 13- and 17-residue alamethicin fragments, labelled with a fluorescent dansyl group at the N-terminus, have been shown to translocate divalent cations across phospholipid membranes and to uncouple oxidative phosphorylation in rat liver mitochondria, in a manner analogous to the parent peptides . From studies of the aqueous phase aggregation behavior of the peptides, as well as their interaction with rat liver mitochondria, it is concluded that the interaction of the peptides with membranes is a complex process, probably involving both aqueous and membrane phase aggregation.

Biochim Biophys Acta, 1981 Dec 7, 649(2), 317 - 24
Adriamycin-induced changes in the surface membrane of sarcoma 180 ascites cells; Murphree SA et al.; Adriamycin increases (a) the rate of agglutination of Sarcoma 180 cells by concanavalin A after brief exposure of 2-3 h and (b) membrane fluidity as measured by ESR within 30 min of exposure at concentrations of the anthracycline of 10(-7)-10(-5) M . The effect of adriamycin on agglutination is not due to an increase in the number of surface receptors for concanavalin A, since the extent of binding of the lectin is not altered by adriamycin and no change occurs in the rate of occupancy of the concanavalin A binding sites by the lectin in cells treated with the antibiotic . The order parameter, a measurement of membrane fluidity, decreases in cells exposed to adriamycin and is dose-related . The results indicate that adriamycin can induce changes in the surface membrane of Sarcoma 180 cells within a brief period of exposure to a low but cytotoxic level of this agent.

Am J Vet Res, 1981 Dec, 42(12), 2114 - 6
Gentamicin tissue concentration in various avian species following recommended dosage therapy; Bush M et al.; Plasma and tissue drug concentrations were compared in eastern bobwhite quail (Colinus virginianus virginianus) and pigeons (Columba livia) given gentamicin by IM administration at the dosage of 10 mg/kg, and in greater sandhill cranes (Grus canadensis tabida) and hybrid rosybill ducks (Netta sp) given the same antibiotic at a dosage of 5 mg/kg . Quail and cranes had significantly higher liver concentrations of gentamicin at 6 hours after injection than did pigeons and ducks . Cranes had significantly higher plasma concentrations than did ducks at 6 hours after injection . Compared with plasma values, gentamicin concentrations were significantly higher in the liver of cranes at 12 hours after injection, and in the kidneys at 18 hours.

Jpn J Antibiot, 1981 Dec, 34(12), 1691 - 6
{Clinical experience with cefroxadine in bacterial infection of children (author's transl)}; Sekiguchi T et al.; In order to evaluate effectiveness of cefroxadine (CXD) in the treatment of bacterial infections of children, the clinical studies were carried out . CXD was orally administered to 30 patients at daily dose of 27.5 approximately 50.0 mg/kg (average 32.3 mg/kg) in 3 approximately 4 divided dose for 3 approximately 10 days (average 4.9 days) . The overall efficacy rate in 30 cases was 93.3%, i.e., excellent 22 (73.3%), good in 6 (20.0%), fair in 1 (3.3%) and poor in 1 case (3.3%) . Drug eruption and transient eosinophilia were observed in 1 case each out of 30 cases (6.7%), but any other abnormality was not observed throughout this series . Based on the above results, CXD was thus considered to be a useful antibiotic in treatment of pediatric infections.

J Antibiot (Tokyo), 1981 Dec, 34(12), 1556 - 61
Xanthocillin X monomethyl ether, a potent inhibitor of prostaglandin biosynthesis; Kitahara N et al.; Xanthocillin X monomethyl ether, known as an antiviral antibiotic, was isolated as a potent inhibitor of Dichotomomyces cejpii . The compound inhibited prostaglandin synthesis from 14C-arachidonic acid in rabbit kidney microsomes by 50% at a concentration of 0.2 microM, while prostaglandin synthesis by microsomes of ram seminal vesicle was inhibited by 50% at 20 microM . The inhibition of xanthocillin X monomethyl ether was reversible . Of the enzymatic steps involved in the synthesis of prostaglandins and thromboxanes tested, conversion of arachidonic acid into prostaglandin H2 was specifically inhibited by xanthocillin X monomethyl ether . Anti-inflammatory activity of this antibiotic on carrageenan-induced oedema in the rat foot was, however, not detectable.

Ann Rheum Dis, 1981 Dec, 40(6), 609 - 11
Septic arthritis in rheumatoid disease causing bilateral shoulder dislocation: diagnosis and treatment assisted by grey scale ultrasonography; Gompels BM et al.; Signs of sepsis may be obscure in patients with rheumatoid arthritis, particularly in association with long-term steroid therapy . If mortality is to be avoided, a high index of suspicion must be maintained for the diagnosis, and doubtful joints should be aspirated for culture and prompt therapy with the correct antibiotic . In this report a patients with advanced rheumatoid arthritis presented with bilateral shoulder dislocation due to septic arthritis . Ultrasonography was particularly helpful in guiding a 20 G needle to fluid collections with the debris-filled joint capsules and in facilitating successful aspiration . Ultrasound also provided a painless, noninvasive, and safe method of serial assessment of the joints after therapy.

Biophys J, 1981 Dec, 36(3), 803 - 9
Voltage-dependent conductance induced by alamethicin-phospholipid conjugates in lipid bilayers; Latorre R et al.; Alamethicin, a linear 20-amino acid antibiotic, forms voltage-dependent channels in lipid bilayer membranes . We show here that alamethicin-phospholipid conjugates can be prepared by photolysis of unilamellar vesicles containing alamethicin and a phosphatidylcholine analogue with a carbene precursor at the end of the C-2 fatty acyl chain . This result indicates that at least a portion of the alamethicin molecule is in contact with the hydrocarbon moiety of the membrane in the absence of an applied voltage . Furthermore, the alamethicin-phospholipid photoproduct is able to induce a voltage-gated conductance similar to that of natural alamethicin . The importance of these results in terms of mechanisms for channel gating is discussed.

Antimicrob Agents Chemother, 1981 Dec, 20(6), 741 - 6
Cefoxitin pharmacokinetics: relation to three different renal clearance studies in patients with various degrees of renal insufficiency; Kampf D et al.; The pharmacokinetics of cefoxitin were examined in 4 healthy volunteers, 6 patients with normal renal function (inulin clearance, greater than 80 ml/min per 1.73 m2), and 35 patients with various degrees of renal insufficiency (inulin clearance, 80 to less than 5 ml/min per 1.73 m2) . A single dose of 30 mg of cefoxitin per kg of body weight was injected intravenously over 3 min . Antibiotic concentrations in plasma were determined by the agar diffusion technique . The cefoxitin half-life increased progressively from 39 min in subjects with normal renal function to 23.5 h in oligoanuric patients . Correspondingly, total body clearance decreased from 340 to 13 ml/min per 1.73 m2 . In addition to the study of cefoxitin kinetics, in 29 of the 41 patients, three different renal clearance tests were performed (inulin, p-aminohippurate, and creatinine clearances) . Of these, p-aminohippurate clearance showed the best correlation with the elimination rate constant beta as well as total body clearance of cefoxitin; but with respect to beta, the differences between the p-aminohippurate and creatinine clearances were quantitatively negligible . Therefore, even in substances which are eliminated predominantly by active tubular secretion, creatinine clearance could be recommended for dosage adjustments.

Laryngoscope, 1981 Dec, 91(12), 1985 - 94
Freedom from ototoxicity in aminoglycoside treated neonates: a mistaken notion; Bernard PA; Pediatricians commonly consider aminoglycoside antibiotics to be less ototoxic in neonates than in adults . This concept is based on the results of pure tone audiometry performed in children treated with aminoglycosides during the neonatal period . However, conflicting results were obtained when using brain stem response audiometry (BSRA) in a group of 26 aminoglycoside treated neonates and a control group of 20 treated neonates during their stays in intensive care units (mean gestational age: 34.6 weeks) . Latencies of wave V significantly differed between the two groups indicating hearing alterations in the treated group . A statistical correlation was demonstrated between initial and final values of wave V and the total doses of antibiotic administered per kilogram of body weight (p less than 0.01) . Most neonates were premature with an immature hearing apparatus . To demonstrate the effect of aminoglycosides on the developing organ of Corti, neonate kittens were chosen as animal models--the onset of hearing occurs 10 days after birth . BSRA was performed every 3 days from birth for 20 days and thereafter every 6 days for the following 30 days . Five kittens treated with a low dose of gentamicin for 20 days were compared with a control group of 5 untreated kittens from the same litters and a group of 5 adult cats receiving the same antibiotic therapy . On the 50th day, all animals were sacrificed and their cochleas were prepared for electron microscopic evaluation . No ultrastructural modifications or BSRA alterations were noted in the adult group . The untreated kittens exhibited a normal pattern of BSRA maturation and their organs of Corti appeared normal . On the contrary, evidence of abnormal hearing maturation and of anatomical damage in the outer hair cells of the first coil of the cochlea was found in the treated kittens . Laboratory findings corroborate our clinical findings that aminoglycoside antibiotics are more ototoxic in neonates than in adult cats.

Am J Surg, 1981 Dec, 142(6), 704 - 6
Primary closure of the contaminated wound . Closed suction wound catheter; Zelko JR et al.; Primary closure of the contaminated wound using a closed suction catheter and antibiotic or povidone-iodine irrigation is cost-effective and convenient alternative to standard open wound care with delayed primary closure . Antibiotic irrigation appeared more effective than povidone-iodine in this study, but the total number of patients studied was too small to be statistically significant.

Am J Surg, 1981 Dec, 142(6), 699 - 703
Intraabdominal abscess after penetrating abdominal trauma; Gibson DM et al.; In 57 (2.4 percent) of 2,416 patients undergoing laparotomy for penetrating abdominal trauma from 1977 to 1980, an intraabdominal abscess developed in the postoperative period . Preoperative antibiotic administration, careful closure of gastrointestinal tract perforation with diversion as necessary, and copious irrigation of the peritoneal cavity at the completion of surgery were common factors in all operations . Over 80 percent of penetrating wounds leading to abscesses occurred in the upper quadrants, and common risk factors included multiple intraabdominal solid organ injuries requiring open drainage, coupled with gastrointestinal tract perforation . Physician delay in the recognition of patients with intraabdominal abscess and in reoperation was a common problem.

Am J Surg, 1981 Dec, 142(6), 664 - 6
Debridement pancreatectomy for pancreatic abscess; Chang FC et al.; Experience with seven cases of pancreatic abscess is reviewed . All patients were treated with radical pancreatic debridement, large sump drainage with postoperative irrigation, gastrointestinal defunctionalization, antibiotic therapy and nutritional support . One patient died, for a mortality rate of 14 percent . We feel that this regimen will help maximize survival in patients with pancreatic abscess.

Proc Natl Acad Sci U S A, 1981 Dec, 78(12), 7276 - 80
Localization of the puromycin binding site on the large ribosomal subunit of Escherichia coli by immunoelectron microscopy; Luhrmann R et al.; By using immunoelectron microscopy, we have localized the binding site on 50S Escherichia coli ribosomal subunits for puromycin, an antibiotic that interacts with the ribosomal peptidyltransferase center . This was achieved by affinity-labeling 50S subunits with N-bromoacetyl puromycin and treating the labeled subunits with an antibody specific for the N6,N6-dimethyladenosine moiety of puromycin . The position of the puromycin binding site was then revealed by localizing the attachment sites of the IgG molecules on the surfaces of the 50S subunits under the electron microscope: it was located at the interface between the subunits, on and around the wider lateral protuberance of the 50S subunit . This localizes directly the peptidyl transferase center on the surface of the large ribosomal subunit.

Klin Monatsbl Augenheilkd, 1981 Dec, 179(6), 411 - 2
{Intraocular infections in perforating eye injuries (author's transl)}; Reich ME et al.; Our of 688 eyes with perforating injuries in 16 cases (2.33%) which were operated on in the years 1973 to 1979, a serious intraocular infection occurred . In 8.94% of the cases in which there were foreign bodies, and in 0.88% of the remaining cases, without intraocular foreign bodies, infection also occurred, although antibiotics were administered prophylactically . With intensive combined antibiotic therapy, and by performing vitrectomy as early as possible it is sometimes possible to save the bulb, and in some cases useful residual function can be achieved . The success of early results of vitrectomy in endophthalmitis recorded in the literature to date could not be obtained as late results in our cases.

Biochem J, 1981 Dec 1, 199(3), 479 - 84
Design, synthesis and DNA-binding capacity of a new peptidic bifunctional intercalating agent; Bernier JL et al.; A lysyl-lysine bifunctional derivative of 9-aminoacridine has been synthesized and its DNA-binding capacity established by electron-paramagnetic-resonance study . For this purpose the binding parameters of a spin-labelled aminoacridine probe were estimated and the affinities of the lysylacridinyl-lysyldiamino-octane dimer and of 9-amino-acridine could be evaluated by competitive assays . The competition study provided quantitative results concerning the dissociation constant (KD) of the dimer . The obtained value was closely similar to the KD of 9-aminoacridine determined by the same method and to the KD previously reported for the anti-tumour and antibiotic bifunctional intercalator quinomycins.

Unfallchirurgie, 1981 Dec, 7(6), 324 - 33
Fast hardening aminoacid-solution as potential carrier of chemotherapeutic agents in the treatment of chronic osteomyelitis; Schultheis KH et al.; Report about an aminoacid, which hardens quickly in liquid environment . It is highly suitable as carrier of chemotherapeutic agents . In-vitro tests show an antibiotic inhibitory activity of different compounds for at least 41 days . According to in-vivo experiments in 17 rats the new substance is replaced in the bone and in soft tissues by fibrous tissue; the antibiotic activity is released slowly . This offers a new carrier which is suitable for occlusion of cavities . The instillation of the new amino-acid (Ethibloc) combined with antibiotics could be a new treatment for chronic osteomyelitis.

Biophys Chem, 1981 Dec, 14(4), 325 - 32
Effects of amphotericin B on membrane permeability--kinetics of spin probe reduction; Aracava Y et al.; The effect of the polyene antibiotic amphotericin B on the permeability of both unilamellar and multilamellar model membranes is investigated . The method measures the loss of the electron paramagnetic resonance signal of a spin probe, trapped in the aqueous compartment of a lipid dispersion, upon addition of ascorbate ions to the bulk aqueous phase . Amphotericin B causes large increases in the permeability of cholesterol-containing egg phosphatidylcholine membranes, whereas the effects are small in the absence of sterol and do not depend on surface charge . The effect of amphotericin depends upon the antibiotic:sterol mole ratio . The antibiotic appears to be unable to cross the membrane, acting only on the outermost bilayer of a multibilayer dispersion . When a phospholipid in the gel phase is used, amphotericin B causes large increases in permeability, independently of the presence or absence of sterol . It is suggested that the mechanism of action of amphotericin B is different for lipids in the liquid crystalline or gel states.

Proc Natl Acad Sci U S A, 1981 Dec, 78(12), 7281 - 4
Mutual interaction between adjacent dG . dC actinomycin binding sites and dA . dT netropsin binding sites on the self-complementary d(C-G-C-G-A-A-T-T-C-G-C-G) duplex in solution; Patel DJ et al.; The Watson-Crick imino protons, the backbone phosphodiester resonances, and the antibiotic exchangeable protons have been used as markers to monitor the separate and simultaneous binding of actinomycin and netropsin to the d(C-G-C-G-A-A-T-T-C-G-C-G) self-complementary duplex in aqueous solution . We demonstrate that intercalation of actinomycin at dG(3'-5')dC sites at either end of the duplex results in a conformational perturbation at the dA . dT tetranucleotide core of the dodecanucleotide duplex . Parallel studies of the groove binding of netropsin at dA . dT sites in the interior of the duplex reveal a conformational perturbation which extends to adjacent dG . dC base pairs in the dodecanucleotide duplex . The NMR markers demonstrate that the d(C-G-C-G-A-A-T-T-C-G-C-G) duplex can accommodate actinomycin and netropsin simultaneously at adjacent dG . dC and dA . dT tetranucleotide blocks along its length with some mutual interaction between neighboring antibiotic binding sites.

J Neurol Neurosurg Psychiatry, 1981 Dec, 44(12), 1104 - 9
Whipple's disease confined to the nervous system; Pollock S et al.; Whipple's disease confined to the nervous system occurred in a 36-year old woman who presented with grand mal seizures and dementia . There was no evidence of extracerebral involvement and the jejunal biopsy was negative before treatment . Multiple enhancing lesions on CT scan progressed despite therapy with minocycline and prednisone, but resolved on treatment with tetracycline . The dementia did not progress while she was on antibiotic therapy . Whipple's disease should be considered as a treatable cause of progressive dementia even in the absence of an abnormal jejunal biopsy.

Biochim Biophys Acta, 1981 Nov 23, 666(2), 284 - 90
The effects of cerulenin on lipid metabolism in vitro in cellular preparations from the rat; Christie WW et al.; The effects of the fatty acid-like antibiotic, cerulenin, on fatty acid biosynthesis in preparations of rat adipocytes and mammary cells in vitro have been investigated . Synthesis of palmitic acid was most strongly inhibited, although the magnitude of the effect was dependent on the nature of the tissue, and was especially diminished in the larger adipocytes from older rats . Cerulenin had no effect on the chain-elongation of preformed fatty acids in any of the tissues studied . Some inhibition of the esterification of preformed palmitic acid was also observed, but this appeared to be due to disruption of the cells rather than direct inhibition of the acyltransferases . It is concluded that cerulenin is a valuable experimental tool in studies of lipogenesis in preparations of intact mammalian cells in vitro.

JAMA, 1981 Nov 13, 246(19), 2163 - 7
Toxic shock syndrome . Evidence of a broad clinical spectrum; Tofte RW et al.; We evaluated various clinical and laboratory manifestations of toxic shock syndrome (TSS) in 17 menstruating females to define the spectrum of illness . Ten women had definite TSS, while seven who satisfied modified case definition criteria had probable TSS . Patients with definite TSS were younger, and symptoms developed later after onset of menstruation than in those with probable TSS . Overall, 16 (94%) had a rash with subsequent desquamation; 15 (88%), myalgias and orthostatic dizziness; 11 (79%), temperature of 38.9 degrees C or higher; 13 (76%), vomiting; 11 (65%), diarrhea; and 7 (54%), hypotension . All patients survived, and acute respiratory or oliguric renal failure possibly related to the absence of shock did not develop in any of them . None had a recurrent episode of TSS after treatment with an antistaphylococcal antibiotic, discontinuing tampon use, or both . Early recognition and treatment of less severely ill women may obviate potentially serious or fatal recurrences of TSS.

Jpn J Antibiot, 1981 Nov, 34(11), 1451 - 6
{Therapeutic effect of ticarcillin against severe infection in patients with hematologic malignancy (author's transl)}; Tsubakio T et al.; Seventy patients with severe infection accompanying hematologic disorders including leukemia and lymphoma were treated with ticarcillin in combination with aminoglycosides and/or cephem derivatives . Of the 58 patients in whom the efficacy could be evaluated, 17 (29%) responded markedly and 22 (38%) moderately, the effective rate being 67% . Side effects attributable to the treatment were noted: rash in 2, fever and rash in 1, vascular pain in 2 (5 and 7 years of age) . Renal and hepatic functions were abnormal in 4 each . However, these abnormal findings were not attributed to ticarcillin . These results indicate that ticarcillin is an effective and safe antibiotic for the treatment of severe infection accompanying hematologic malignancy when used in combination with aminoglycosides and/or cephem derivatives.

Antibiotiki, 1981 Nov, 26(11), 825 - 8
{Sisomicin . The mechanism of admixture inactivation and formation}; Kartseva VD et al.; Inactivation of sisomicin in aqueous solutions was studied under various conditions . At pH 4-10 and a temperature of 60 degrees C the inactivation rate constant was equal to (5-10) X 10(-5) hour-1 and remained stable . At lower pH values the inactivation rate constant increased: 5.5 10(-3) (60 degrees C) at pH 0.5 . The activation energy of the inactivation reaction was 27 (pH 0.5) and 32 (pH 4.0) kcal/mol . The study on the behaviour of sisomicin in solutions with different pH values under the environmental conditions and in the atmosphere of nitrogen showed that at low pH values the inactivation was mainly determined by hydrolysis of the glycoside bond . Formation of coloured compounds did not include the oxidation reaction . At pH about 7.0 oxidation of the antibiotic or of the products of its degradation with respect to the double bond played a significant role in the inactivation and formation of the coloured substances.

Z Urol Nephrol, 1981 Nov, 74(11), 835 - 6
{Subpelvic contrast medium extravasation after urography}; Brunzema F; Spontaneous extravasation of contrast medium after X-ray examinations of low ureteroliths is not an exceptionally infrequent occurrence . A patchy stripe of contrast medium, parallel to the M . psoas is the noticeable radiological indication . With our patients brief clinical observation under antibiotic protection has been sufficient . Check-up urography has later shown normal conditions . Adhesions and obstructions in the region of the exit from the renal pelvis have not been found in check-ups to date . We have never found it necessary to operate because of these changes.

In Vitro, 1981 Nov, 17(11), 993 - 6
Elimination of Mycoplasma hyorhinis infections from four cell lines; Gurney T Jr et al.; Four monolayer mammalian cell lines were cured of Mycoplasma hyorhinis infections by cloning in microtiter dishes in the presence of tetracycline and kanamycin . During cloning, cultures were refed with fresh antibiotic containing medium every 2 or 3 d for 14 day and were then cultured without effective antibiotics for at least 21 d . From the four lines we recovered 29 clones, none of which were infected after treatment as judged by the lack of extranuclear fluorescence after staining with the fluorochrome Hoechst 33258, and by normal autoradiographic labeling of the cells by tritiated nucleosides . One clone from each line was tested further by attempted culture of mycoplasmas and was also judged to be uninfected . Infection has not reappeared in any of the clones after extensive culture in the absence of the effective antibiotics.

J Clin Microbiol, 1981 Nov, 14(5), 571 - 3
Infection of a brain abscess of Mycoplasma hominis; Payan DG et al.; Persistent fever in a young man after evacuation of a subdural hematoma caused by a depressed skull fracture made it necessary to carry out a computerized tomographic exam of the head that demonstrated a left frontal lobe brain abscess . Mycoplasma hominis was recovered from this abscess as the sole infecting organism . Serial computerized tomographic scans showed resolution after aspiration and antibiotic therapy.

Farmaco {Sci}, 1981 Nov, 36(11), 916 - 20
Synthesis of 7-{7-(2-thienylacetamido)-cephalosporanamido}cephalosporanic and 6-{7-(2-thienylacetamido)cephalosporanamido}-penicillanic acids; Mazzeo P et al.; The synthesis of some molecules containing two moieties with potential antibiotic activity is described . These compounds were obtained by acylation of esters of 7-aminocephalosporanic and 6-aminopenicillanic acids with beta-lactam antibiotics.

Am J Med, 1981 Nov, 71(5), 900 - 2
Pyomyositis: tropical disease in a temperate climate; Schlech WF 3rd et al.; Two cases of pyomyositis or bacterial abscess of striated muscle in adults are presented . One patient was initially diagnosed as having acute thrombophlebitis of the lower extremity . Computerized tomography was helpful in establishing the correct diagnosis . The other patient presented with a closed compartment syndrome following blunt trauma . Both patients responded to open drainage and antibiotic therapy, although the diagnosis was delayed for over three weeks in one patient . Although common in the tropics, pyomyositis is unusual in the temperate zone . Unfamiliarity with this entity remains the major obstacle to appropriate management.

Am J Hosp Pharm, 1981 Nov, 38(11), 1743 - 5
Effect of microwave radiation on the stability of frozen cefoxitin sodium solution in plastic bags; Stiles ML; The effect of microwave radiation on the stability of frozen cefoxitin sodium solutions was investigated . The i.v . fluids used as vehicles for the 1-g admixtures of cefoxitin sodium were 5% dextrose injection and 0.9% sodium chloride injection in 50-ml and 100-ml polyvinyl chloride flexible containers . The antibiotic small-volume parenteral solutions were frozen at -20 degrees C for 72 hours and thawed by microwave radiation . Before and after the freeze-thaw process, the solutions were observed for changes in appearance with a light and dark field visual surveillance technique . In addition, pH determinations were made with a microprocessor ionanalyzer, and high-performance liquid chromatographic determinations of concentration were performed . No significant drug concentration changes were detected and no visible changes were observed . The pH changes were minimal . Microwave radiation can reduce thawing time of antibiotic admixtures . In this study, the stability of cefoxitin sodium solutions was not affected by the freeze-thaw process.

J Bacteriol, 1981 Nov, 148(2), 534 - 40
Regular segregation of composite plasmid Rms201; Ike Y et al.; Copy number mutants Rms201ts15 and Rms201ts16 were isolated at 30 degrees C from a temperature-sensitive replication mutant (Rms201ts14) of the conjugative plasmid Rms201 . The numbers of plasmids per chromosome of ML1410(Rms201ts14), ML1410(Rms201ts15), and ML1410(Rms201ts16) grown at 30 degrees C were 2.2, 7.4, and 20, respectively . The synthesis of covalently closed circular plasmid deoxyribonucleic acid stopped in Rms201ts14, Rms201ts15, and Rms201ts16 immediately after a "shift-up" in temperature (42 degrees C) . At 42 degrees C, antibiotic-sensitive derivatives appeared after a certain lag time: the lag times of ML1410(Rms201ts14), ML1410(Rms201ts15), and ML1410(Rms201ts16) were 2.5, 5, and 6.8 generations, respectively . After these times, plasmid-positive cells in the populations decreased at a rate of about 50% per generation in all of the mutants . From these results we conclude that plasmid segregation (partition) of Rms201 occurs by regular segregation (partition).

Cancer Treat Rep, 1981 Nov-Dec, 65(11-12), 987 - 93
VP-16-213 in the treatment of stage III and IV diffuse lymphocytic lymphoma of the large cell (histiocytic) variety: an interim report; Jacobs P et al.; A pilot study has previously demonstrated antitumor activity for the epipodophyllotoxin VP-16-213 in patients with diffuse lymphocytic lymphoma of the large cell (histiocytic) variety . To define this observation further, a prospective randomized trial was undertaken in patients with stage III and IV disease, comparing this agent used alone (group 1, 41 patients) to the response obtained when the same schedule of VP-16-213 was combined with either cyclophosphamide (group 2, 36 patients) or doxorubicin (group 3, 41 patients) . The quantity of VP-16-213 given to patients in the three groups was equivalent . Of these 118 patients, three were lost to followup and thus were excluded from further study . Specifically included were 12 patients who died within 1 month of diagnosis while still receiving induction chemotherapy . For the three groups, complete remission rates were 39%, 26%, and 54%, and additional partial remissions were obtained in 20%, 11%, and 10% of the patients, respectively . The lower remission rates obtained in patients receiving cyclophosphamide combined with VP-16-213 are statistically significant (P less than 0.05), but no explanation for this is evident since the distribution of poor prognostic factors among the three groups was uniform . The higher percent of complete remission and the greater number of patients remaining free from disease in group 3 demonstrate the superiority of the combination of VP-16-213 with the anthracycline antibiotic doxorubicin.

What Is Pcr?, What Is Fermentation?, What Is Biofilm?, What Is Rhizobia?, What Is Antibiotic?, r, Bacteriology, n, Bacterium, a, Microbe, s, Microorganisms, r, Microbes, n, Escherichia coli, r, Yeasts, r, Bacillus, s, Rhodococci, i, Penicillin, i, Streptococcal, n, Bacteria, n, Yeasts, c, Gram negative, o, Escherichia coli, e, S. cerevisiae, e, Petri dish, n, Staphylococcus aureus, s, Escherichia coli, a, Staphylococcus aureus, i, Escherichia coli, o, Proteus, i, Salmonella, o, Escherichia coli, c, Micrococci, r, Bacillus

Scientific Publications - Work Done by Microbiology Reader Bioscreen C
Agricultural Microbiology Anaerobic Microbiology Antimicrobial Susceptibility Artificial Atmosphere Bioassay of Antibiotics Biofilm Microbiology Bioreactor Technology Biotechnology Cell Biology Clinical Microbiology Environmental Microbiology Experiments with Yeast	Fermentation Food Microbiology Functional Genomics Gene Technology Growth Media Development Growth Rate and Lag Time Industrial Microbiology Medical/Pharmaceutical Field Microbiological Assay Microbiological Research Microbiology of Cosmetics go to a specific theme...	Military Microbiology Molecular Microbiology Mutagenicity and Genotoxicity Oral Microbiology Patents Postantibiotic Studies Soil Microbiology Spore Microbiology Veterinary Microbiology Waste/Wastewater Treatment Water Microbiology Wine Microbiology

� 2005 Transgalactic Ltd (manufacturer of Bioscreen C software) | Privacy Statement | P.O. Box 1393, 00101 Helsinki, Finland, phone: +358 9 85172920, fax: +358 9 8749481, e-mail: microbiology@bionewsonline.com

Last modified: May 25, 2005