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| Jpn J Pharmacol, 1989 Dec, 51(4), 465 - 73 Studies on the nephrotoxicity of aminoglycoside antibiotics and protection from these effects (7): Effect of latamoxef on binding of tobramycin to brush border membranes isolated from rat kidney cortex; Kojima R et al.; We investigated the effect of latamoxef (LMOX) on the binding of tobramycin (TOB) to brush border membranes (BBMs) isolated from rat kidney cortex by calcium precipitation . The simultaneous treatment with TOB (0.2 mM) and LMOX (10 and 20 mM) to the BBMs fraction (about 250 micrograms protein) significantly inhibited the binding of TOB to BBMs . The addition of the reaction mixture of TOB (0.2 mM) and LMOX (4, 10 and 20 mM) which was preincubated for 3 hr at 37 degrees C, to the BBMs fraction resulted in less binding of TOB to the membranes than that observed in the case of simultaneous treatment with both drugs . Although {14C}-labeled LMOX was taken up by BBMs temperature- and time-dependently, the pretreatment with LMOX showed no obvious differences in inhibition of the TOB binding to BBMs, as compared with the result from simultaneous treatment with both drugs . Additionally, the binding of TOB to the LMOX-treated BBMs that were resuspended in fresh medium after the pretreatment with LMOX for 10 min at 37 degrees C was similar to that of TOB to the non-treated BBMs . These results indicate that LMOX inhibits the binding of TOB to BBMs not by binding to BBMs but by interacting with TOB. J Clin Pathol, 1989 Dec, 42(12), 1255 - 8 Antibiotic resistant fever associated with herpes simplex virus infection in neutropenic patients with haematological malignancy; Baglin TP et al.; The incidence of mucocutaneous herpes simplex virus infection confirmed by culture and occurring during febrile neutropenic episodes was determined in 43 patients with haematological malignancy . The outcome of 72 episodes of neutropenic fever was determined and correlated with the presence or absence of herpes simplex virus (HSV) infection . Twenty four patients had mucocutaneous HSV infection during at least one episode . In 24 episodes in which HSV was isolated only 12.5% of fevers responded to antibiotics and 75% of fevers were otherwise unexplained . Conversely, in 48 episodes of neutropenic fever in which HSV was not isolated 67% of fevers responded to antibiotics and only 8.3% were unexplained . The difference in incidence of antibiotic resistant fever in the two groups was significant . There was, therefore, a strong association between mucocutaneous HSV infection and antibiotic resistant fever in immunosuppressed neutropenic patients . As most HSV infections are the result of virus reactivation, establishing the HSV serological state of patients would identify those at risk of infection and hence those in whom the prophylactic use of acyclovir would be indicated. Ann Emerg Med, 1989 Dec, 18(12), 1339 - 43 Antibiotic therapy of life-threatening infectious diseases in the emergency department; Lauter CB; Initial therapy in acutely ill septic patients is necessarily empiric . Although a specific etiologic infectious diagnosis is rarely made in an acute situation, a treatment decision must be made and must be developed from history, physical examination, and minimal laboratory and roentgen studies . Three life-threatening syndromes are discussed: febrile-neutropenic patients with cancer, immunosuppressed patients with fever and lung infiltrates, and patients with acute community-acquired meningitis. Antimicrob Agents Chemother, 1989 Dec, 33(12), 2101 - 8 Reactivation of peptidoglycan synthesis in ether-permeabilized Escherichia coli after inhibition by beta-lactam antibiotics; Talbot MK et al.; The recovery of peptidoglycan-synthesizing activity after inhibition by beta-lactam antibiotics was investigated in ether-permeabilized cells of Escherichia coli B . Such cells synthesize sodium dodecyl sulfate-insoluble peptidoglycan when provided with UDP-linked precursors and Mg2+ . The ability of beta-lactam antibiotics to inhibit the synthesis of peptidoglycan was correlated with their affinity for penicillin-binding proteins 1A and 1Bs . Penicillin-binding protein 1Bs is thought to be the major peptidoglycan synthetase in E . coli and is a major lethal target for beta-lactam antibiotics . Ether-treated bacteria were preincubated with concentrations of beta-lactams sufficient to completely inhibit peptidoglycan synthesis and then treated with beta-lactamases to inactivate free antibiotic prior to measurement of peptidoglycan synthesis . At 40 min after beta-lactamase treatment, the rate of peptidoglycan synthesis was about 74% of the control rate in cells pretreated with ampicillin, but only 15% of the control in cells pretreated with penicillin G or azlocillin . Reversal of inhibition by several other antibiotics fell between these extremes . When cross-linking of peptidoglycan was measured specifically, reversal of inhibition by ampicillin also occurred more readily than that by penicillin G . Reactivation of peptidoglycan synthesis was not due to de novo synthesis of penicillin-binding proteins since it occurred under conditions that did not allow incorporation of {14C}leucine . We conclude that there is considerable variation in the stability of the inactive acyl enzymes formed between various beta-lactams and penicillin-binding protein 1Bs, with those formed by penicillin G being relatively long-lived. Aichi Gakuin Daigaku Shigakkai Shi, 1989 Dec, 27(4), 1071 - 9 {Two cases of intra-arterial infusion of antibiotics in intractable chronic osteomyelitis of the mandible}; Suzuki A et al.; Two cases of intractable chronic osteomyelitis of the mandible were encountered recently . The first of these was a 51-year-old man who complained of swelling in the right cheek and the mandibular region . The other was a 27-year-old man who chiefly complained of swelling, pain and trisms in the right mandible . Both patients were treated with antibiotics and the osteosclerotic tissue was removed . The antibiotics were injected into the superficial temporal artery using a one-shot technique . Radiographs of the patients taken one to two years after the treatment revealed normal conditions with no signs of recurrence . It appears that this form of treatment is effective in the case of intractable chronic osteomyelitis of the mandible. Ann Trop Paediatr, 1989 Dec, 9(4), 256 - 60 Incidence of multiple antibiotic resistances in organisms isolated from cases of infantile diarrhoea in a Nigerian oral rehydration therapy clinic; Lamikanra A et al.; A total of 247 bacterial isolates were obtained from diarrhoeal patients aged 0-60 months in an oral rehydration therapy clinic in Ibadan and tested for sensitivity to 11 antibiotics using the disc diffusion method . Fifty isolates obtained from apparently healthy age-matched controls were similarly tested . The results show that 6(2.4%) of the isolates obtained from the diarrhoeal children were resistant to all the 11 antibiotics used in the test and that most of the others were resistant to several antibiotics . Similarly, a very considerable percentage of isolates obtained from children in the control group were found to be resistant to several antibiotics . It is therefore apparent that there is a high incidence of multiply-antibiotic-resistant isolates within the sample environment. Biochemistry, 1989 Nov 28, 28(24), 9392 - 8 Hypelcin A, an alpha-aminoisobutyric acid containing antibiotic peptide, induced permeability change of phosphatidylcholine bilayers; Matsuzaki K et al.; Interactions of hypelcin A, an alpha-aminoisobutyric acid containing antibiotic peptide, with phosphatidylcholine vesicles were investigated to obtain information on its bioactive mechanism . The peptide induced the leakage of a fluorescent dye, calcein, entrapped in sonicated vesicles . The leakage rate depended on both the peptide and the lipid concentrations . Analysis of this dependency indicated that the leakage was due to the monomeric peptide and that the membrane-perturbing activity of the monomer was higher for solid distearoylphosphatidylcholine vesicles than for fluid egg yolk phosphatidylcholine vesicles . Hypelcin A also affected the gel to liquid-crystalline phase transition of dipalmitoylphosphatidylcholine multilamellar vesicles . The transition was broadened with a reduced transition enthalpy, suggesting the peptide strongly binds the surrounding lipids to perturb the bilayer lipid packing . A circular dichroism study revealed that the helical content of hypelcin A increases upon membrane binding . We concluded that the monomeric peptide with an increased helical content, complexed with the lipids, perturbs the lipid organization and induces the increased permeability. Mol Cell Biochem, 1989 Nov 23-Dec 19, 91(1-2), 39 - 44 Membrane effects of the polyene antibiotic amphotericin B and of some of its derivatives on lymphocytes; Henry-Toulme N et al.; Amphotericin B (AmB) exhibits immunomodulating properties in mice . In vitro studies on lymphocytes, in relation with these properties, are reported here with AmB and two of its derivatives: the N-Fructosyl (N-Fru AmB) and the N-thiopropionyl (AmBSH) derivatives . Interactions of these molecules with thymocytes, a sensitive cell type, demonstrated that the extent of binding is not a toxicity parameter . In contrast, membrane fluidity changes have been observed and appeared to be related to toxicity . Experiments performed with normal B lymphocytes have shown that Amphotericin B derivatives were more potent polyclonal B cell activators than the parent compound . To go further in the understanding of these events, we have investigated in a B cell line WEHI 231, the changes in intracellular Ca2+ and membrane potential induced by AmB and AmBSH . The two polyenes were shown to induce membrane depolarization but no intracellular Ca2+ increase. Biochem Biophys Res Commun, 1989 Nov 15, 164(3), 1281 - 7 Effect of anthracycline antibiotics on the reconstituted mitochondrial tricarboxylate carrier; Stipani I et al.; The effect of anthracycline antibiotics on the activity of the partially purified and reconstituted tricarboxylate carrier system of the rat liver mitochondria was studied . It was found that the citrate/citrate exchange activity is inhibited by Br-daunomycin and with less potency by doxorubicin, daunomycin, epirubicin and idarubicin . The inhibition of the citrate transport activity is concentration and time-dependent . Cardiolipin protects against the inhibition by Br-daunomycin and the reconstituted citrate transport activity depends upon the ratio of cardiolipin/Br-daunomycin. Clin Ter, 1989 Nov 15, 131(3), 177 - 82 {Bacterial infections in cancer patients without neutropenia . Comparison between 2 antibiotic combinations (aztreonam and oxacillin versus cefoxitin and tobramycin)}; Apice G et al.; In the treatment of infections arisen in neoplastic patients without neutropenia, 2 antibiotic combinations (aztreonam + oxacillin vs tobramycin + cefoxitin), have been compared with regard to therapeutic effectiveness and tolerability . Twenty patients (age: 30-75) have been studied . Tolerability of both combinations was excellent . Results of this study showed a lower percentage of superinfections and a higher percentage of cure in patients treated with the combination aztreonam + oxacillin, even if the data were not statistically significant. Am J Surg, 1989 Nov, 158(5), 435 - 7 Antibiotic irrigation and the formation of intraabdominal adhesions; Rappaport WD et al.; The efficacy of antibiotic peritoneal lavage in the prevention of postoperative infection is controversial . The role of intraperitoneally administered cefazolin and tetracycline in the formation of adhesions was studied in the rodent model . Thirty-two rats were divided into 3 groups . Group 1 underwent midline laparotomy with instillation of 10 ml of normal saline solution . Group 2 and Group 3 underwent the same procedure with instillation of 0.2 percent saline solutions of cefazolin or tetracycline, respectively . Animals were sacrificed after 2 weeks . Intraabdominal adhesions were graded and samples of parietal peritoneum were processed for histologic data . Group 2 and Group 3 had significantly higher adhesion scores compared with Group 1 (p less than 0.001) . Histologic appearance of both antibiotic-irrigated groups showed mesothelial thickening with presence of fibroblasts and collagen . Cefazolin and tetracycline irrigation of the abdominal cavity contributes to the formation of peritoneal adhesions in the rat model. Bioorg Khim, 1989 Nov, 15(11), 1445 - 61 {A promising search for substances, suppressing the development of the human immunodeficiency virus, among natural and semisynthetic antibiotics}; Preobrazhenskaia MN; Perspectives of search, among natural and semisynthetic antibiotics, for inhibitors of different stages of the human immunodeficiency virus replication are discussed . The compounds which inhibit the virus absorbtion, reverse transcription, viral mRNA synthesis, viral protein translation or viral glycoprotein processing are presented. J Clin Periodontol, 1989 Nov, 16(10), 647 - 53 Effect of non-surgical periodontal therapy combined with adjunctive antibiotics in subjects with "refractory" periodontal disease . (I) . Clinical results; Magnusson I et al.; The aim of the present study was to evaluate the clinical effect of non-surgical periodontal therapy with the adjunct of a selected antibiotic in subjects with refractory periodontitis . 10 subjects were selected for the study; all had a history of periodontal surgery, tetracycline therapy, and regular maintenance by a periodontist . Clinical registrations including gingival index, plaque index, presence of bleeding and suppuration, pocket depth, and duplicate measurements of attachment level were performed at baseline and at monthly intervals . When disease activity was detected based on the tolerance method, a bacterial sample was taken from the active site and its susceptibilities to a number of antibiotics were determined . For the selected 10 subjects, Augmentin was the antibiotic of choice . Each subject received 750 mg/day for 2 weeks, during which time a full-month scaling and root planing was performed under local anesthesia . Clinical re-evaluation was performed after 3, 6, 9 and 12 months . At the time disease activity was detected, the average loss of attachment at all active sites was 2.2 mm, and the increase in pocket depth 1.5 mm . At 3 months post-therapy, these sites had regained 2 mm of attachment which remained stable through the 12-month examination . Pocket depths decreased 2.5 mm over the first 6 months and then stabilized . The frequency of all sites that gained 1 mm or more of attachment increased by approximately 10% over the first 9 months following therapy . The frequency of all sites that decreased 1 mm or more in pocket depth increased approximately 15% over the same period.(ABSTRACT TRUNCATED AT 250 WORDS) Antibiot Khimioter, 1989 Nov, 34(11), 853 - 5 {Status of the adenine system of the rat liver after administration of anthracycline antibiotics}; Ermolitskaia GR et al.; Changes in the content and ratio of various components of the adenylate system were followed up in the liver of rats after their exposure to doxorubicin and daunorubicin in the time course of 35 days . The shifts detected in various periods after the exposure must be due to different regulatory mechanisms . By the end of the experiment (on day 35) there was a tendency to normalization of the indices. Antibiot Khimioter, 1989 Nov, 34(11), 849 - 52 {Comparative study of the cytotoxic effects of anthracycline antibiotics on heterotransplants of human breast cancer cultivated in diffusion chambers in vivo}; Krutova TV et al.; Cytotoxic activity of doxorubicin, daunomycin, carminomycin and ruboxyl against 50 human breast cancer heterotransplants in diffusion chambers was studied . The effect was estimated autoradiographically on the 6th or the 7th day of the cultivation after the drug administration in the maximum tolerance doses . The tumors were considered sensitive when the labeling index of their transplants after the treatment appeared to be reduced by 50 or less per cent against the control . The number of the tumors sensitive to all the drugs amounted to 72-80 per cent . 19 tumors were sensitive to 4 antibiotics . 14 and 8 tumors were sensitive to 3 and 2 antibiotics, respectively, and only 1 tumor was sensitive to 1 drug . The sensitivity significantly correlated with the initial labeling index of the primary tumors and their heterotransplants . The results suggested that daunomycin and ruboxyl possessed a high cytotoxic activity close to that of doxorubicin and carminomycin and might be recommended for clinical trials in the treatment of patients with breast cancer. Mikrobiol Zh, 1989 Nov-Dec, 51(6), 79 - 83 {The isolation and characteristics of antibiotic-containing liposomes}; Rotov KA et al.; The results of studies on the incorporation of a number of antibiotics into liposomes and the use of gamma irradiation for sterilization of phospholipid vesicles are presented . The toxicity of hydrochloride tetracyclin in free and liposomal forms is estimated for golden hamster with different methods of administration. Xenobiotica, 1989 Nov, 19(11), 1285 - 95 Metabolism of dihydroergotamine by a cytochrome P-450 similar to that involved in the metabolism of macrolide antibiotics; Delaforge M et al.; 1 . Previous studies have shown that the macrolide antibiotics, such as oleandomycin and erythromycin, enhance their own transformation into a stable metabolite-cytochrome P-450 complex, thus impairing monooxygenase activity . This cytochrome P-450 induced by macrolides is similar to the major form induced in rats by pregnenolone-16 alpha-carbonitrile (PCN) (III A1 isozyme) . 2 . The cytochrome P-450 isozyme induced in rats by PCN or macrolide antibiotics bound dihydroergotamine (DHE) with high affinity and was also capable of metabolizing the drug . However, phenobarbital administration enhanced the metabolism of DHE to a greater extent than would be expected from the levels of the PB-PCNE isoenzyme, indicating that other cytochrome P-450 proteins may also be involved in DHE metabolism . 3 . DHE metabolism was inhibited by macrolide antibiotics both ex vivo and in vitro . The metabolite-cytochrome P-450 complex formed by the antibiotics impairs the metabolism of DHE, so that when the complex is dissociated the metabolic activity is restored . These findings explain the observed clinical interactions between macrolides and other drugs, and such an approach may prove useful in their prediction. J Clin Periodontol, 1989 Nov, 16(10), 621 - 4 Effect of adhesive antibiotic TA on plaque and gingivitis in man; Manor A et al.; The adhesive antibiotic TA was applied to the dento-gingival junction of 8 human volunteers, suffering from moderate to severe gingivitis . 2 diametrically opposed quadrants of the mouth received 4 applications of 0.1 mg TA, while the other 2 quadrants were treated with a placebo and served as controls . The plaque index, gingival index and bleeding index were scored periodically for 2 weeks and in 4 patients for up to 30 days . The TA-treated quadrants showed a rapid decrease in all 3 indices following 2 treatments . A further improvement was observed with the 3rd and 4th treatments . 30 days after the onset of the experiment and 23 days after the last application, the indices were still considerably lower than the initial values. J Biochem (Tokyo), 1989 Nov, 106(5), 794 - 7 Biochemical mechanisms of aminoglycoside cell toxicity . II . Accumulation of phospholipids during myeloid body formation and histological studies on myeloid bodies using twelve aminoglycoside antibiotics; Oshima M et al.; Cultured human skin fibroblasts take up aminoglycoside antibiotics into lysosomes to form myeloid bodies . Gentamicin (GM), one such antibiotic, was taken up until the cellular concentration reached an estimated 64 mM on the 3rd day when cells were incubated with 2 mM gentamicin . The rate of release of intracellular GM was high on the first day of incubation and gradually slowed down over the next 4 d . About 50% of the GM remained in the cells even on longer incubation in GM-free medium, suggesting it may irreversibly bind to cellular components . With myeloid body formation, the cellular phospholipid content increased 1.5 times . Bis(monoacyl-glyceryl)phosphate, which is known as a marker of lysosomal phospholipid, phosphatidylcholine and phosphatidylserine showed 250, 162, and 153% increases, respectively . Sphingomyelin was not accumulated, while lysosomal sphingomyelinase was dramatically inhibited . Of 12 different aminoglycoside antibiotics, paromomycin is the most prominent myeloid body-forming antibiotic . The myeloid body-formation is not directly correlated to human nephrotoxicity . On the other hand, the number of myeloid bodies is well correlated to the affinity to the brush border membrane, suggesting that such aminoglycoside antibiotics are taken up easily through cellular endocytosis . The cytotoxic effects of aminoglycoside antibiotics may be due to by their binding to cellular organelles other than lysosomes. Infection, 1989 Nov-Dec, 17(6), 355 - 9 Survival of Borrelia burgdorferi in antibiotically treated patients with Lyme borreliosis; Preac-Mursic V et al.; The persistence of Borrelia burgdorferi in patients treated with antibiotics is described . The diagnosis of Lyme disease is based on clinical symptoms, epidemiology and specific IgG and IgM antibody titers to B . burgdorferi in serum . Antibiotic therapy may abrogate the antibody response to the infection as shown in our patients . B . burgdorferi may persist as shown by positive culture in MKP-medium; patients may have subclinical or clinical disease without diagnostic antibody titers to B . burgdorferi . We conclude that early stage of the disease as well as chronic Lyme disease with persistence of B . burgdorferi after antibiotic therapy cannot be excluded when the serum is negative for antibodies against B . burgdorferi. Vrach Delo, 1989 Nov, (11), 120 - 1 {The use of antibiotics in outpatient practice}; Mal'tsev VI et al.; The authors describe the tactics of using antibiotics in out-patient conditions . In acute bacterial infection the most adapted to the pathogen and infections focus antibiotic is used . The problem of indication to antibiotic therapy is discussed . Of importance is avoidance of the development of resistant strains . Monotherapy with antibiotics of selective narrow spectrum is advocated . The local use of antibiotics is to be avoided. Pediatr Infect Dis J, 1989 Nov, 8(11), 780 - 7 Anatomic and audiologic sequelae after tympanostomy tube insertion or prolonged antibiotic therapy for otitis media; Pichichero ME et al.; In this study the anatomic and hearing sequelae are characterized for 43 children (86 ears) with recurrent acute otitis media and/or persistent otitis media with effusion who had received three or more tympanostomy tube placements and 46 children (92 ears) managed medically with repeated courses of therapeutic and/or or prophylactic antibiotics . In the surgical group 311 tympanostomy tube surgeries had been performed and in the medical group 1334 episodes of acute otitis media and/or 186 episodes of otitis media with effusion occurred . Tympanosclerosis was found in 6.5% of the medical group ears and 52.3% of the surgical group ears . Tympanic atrophy occurred in 4.3% of the medical group ears and 40.7% of the surgical group ears . The duration of the presence of the tympanostomy tube significantly influenced the tympanic membrane . The presence of middle ear fluid at the time of tube insertion, particularly high viscosity ("glue") fluid, correlated with persisting sclerosis (P less than 0.00001) and reduced tympanic membrane mobility (P less than 0.00001) but not tympanic membrane atrophy (P = 0.94) later . Abnormal hearing, defined as a hearing threshold greater than 20 dB occurred in 9.3 to 18.7% of the surgical ears and in 3.7 to 9.0% of the medical ears depending on the hearing frequency tested . Medical management consisting of recurrent use of therapeutic and/or prophylactic antibiotics was associated with infrequent anatomic and audiologic sequelae . Repeated placement of tympanostomy tubes may be associated with the frequent occurrence of both anatomic and audiologic sequelae. Br Vet J, 1989 Nov-Dec, 145(6), 552 - 7 Antibiotic persistence and tolerance in the lactating sheep following a course of intramammary therapy; Buswell JF et al.; The commercial use of sheep for the production of milk and milk products is attractive to farmers actively diversifying their dairy interests due to the impact of the quota system . As intensification of milking increases, flock sizes will enlarge and the incidence of ovine mastitis will inevitably increase . The pharmaceutical industry and the veterinary practitioner will be required to provide advice and data upon the performance of currently available bovine intramammary preparations for the sheep . This study produces evidence to confirm that one available bovine intramammary preparation, when infused into milking sheep, produced a withholding time approximately three times as long as that defined for the cow . Following a course of three infusions over a period of 24 hours after consecutive milkings, milk was not acceptable for human consumption or for the production of cheese and yoghurts until 136 hours following the final infusion . This situation is likely to be representative of that which will occur with other intramammary products used in the ovine species following infusion with bovine intramammary preparations. Berl Munch Tierarztl Wochenschr, 1989 Nov 1, 102(11), 371 - 4 {The effect of combined antibiotic and immune prophylaxis against atrophic rhinitis on the body weight of swine}; Bilkei G; In a natural outbreak of Atrophic Rhinitis, the weaned piglets were divided into four groups . Group 1 (10 weaned piglets); Their mother was vaccinated with 2 ml Rhinipig i . m . 3 weeks prior to farrowing . The piglets received 0.2 ml each of Pargenta 50 (= 10 mg Gentamycin) k . m . on the third, fifth and seventh days after birth . The piglets were fed a food containing 10 ppm Gentamycin base during the 6 weeks following their weaning . Group 2 (10 weaned piglets); Their mother was vaccinated with 2 ml Rhinipig i . m . 3 weeks prior to farrowing . The piglets received 0.2 ml each of Pargenta 50 (= 10 mg Gentamycin) i . m . on the third, fifth and seventh days after birth . Group 3 (10 weaned piglets); Their mother was vaccinated with 2 ml Rhinipig i . m . 3 weeks prior to farrowing . Group 4 (10 weaned piglets, untreated, experimental control group) . The results were during the growing period (from 12.3 kg to 32-34.9 kg) and during the finishing period (from 32-34.9 kg to 100 kg) evaluated . Group 1 showed significantly better food conversion and daily weight gain in both periods when compared to the other groups . Although the difference of daily weight gain between Group 1 and Groups 2 and 3 where diminished by 4.34% respectively 1.72%. J Trauma, 1989 Nov, 29(11), 1462 - 8; discussion 1468-70 Pharmacokinetic monitoring of nephrotoxic antibiotics in surgical intensive care patients; Reed RL 2nd et al.; An assessment of the dosage regimens prescribed for potentially nephrotoxic antibiotics (amikacin, gentamicin, tobramycin, and vancomycin) was undertaken on surgical intensive care unit patients . In 166 patients, 224 series of blood antibiotic level determinations were obtained . Using individualized pharmacokinetic determinations, the regimens were revised as necessary to provide optimal blood levels . Because of variable volumes of distribution and elimination rates, dosing according to standard clinical guidelines produced significantly lower peaks than did pharmacokinetically determined regimens for gentamicin (p less than 0.005), tobramycin (p less than 0.0001), and vancomycin (p less than 0.05) . Importantly, fewer patients achieved therapeutic levels with the original regimens than with the revised regimens for gentamicin (9% vs . 91%, p less than 0.0005), tobramycin (27% vs . 92%, p less than 0.0001), and vancomycin (30% vs . 69%, p less than 0.0001) . Individualized pharmacokinetic analysis of potentially nephrotoxic antibiotics in critically ill patients is essential if therapeutic, non-toxic levels are to be maintained. J Antibiot (Tokyo), 1989 Nov, 42(11), 1643 - 8 1H and 13C NMR assignments of the thiopeptide antibiotic nosiheptide; Mocek U et al.; The 1H and 13C NMR spectra of nosiheptide have been assigned by use of 2D NMR techniques on unlabeled samples and biosynthetically multiple-labeled samples from stable isotope feeding experiments. J Antibiot (Tokyo), 1989 Nov, 42(11), 1639 - 42 The structure of vacidin A, an aromatic heptaene macrolide antibiotic . II . Stereochemistry of the antibiotic; Sowinski P et al.; On the basis of coupling constants and rotating frame nuclear Overhauser effect spectroscopy of vacidin A methoxycarbonylmethylamide, the stereochemistry of the antibiotic was established . The configuration of the aglycone was determined as (3R,7R,9R,11S,13S,15R,17S,18R,19S,21R, 36S,37R,38S) . The aminosugar constituent of the antibiotic was identified as beta-(D)-mycosamine . The chiral center at C-41 remains to be assigned. J Antibiot (Tokyo), 1989 Nov, 42(11), 1631 - 8 The structure of vacidin A, an aromatic heptaene macrolide antibiotic . I . Complete assignment of the 1H NMR spectrum and geometry of the polyene chromophore; Sowinski P et al.; The constitution of vacidin A, a representative of the aromatic heptaene macrolide antibiotics was established on the basis of 13C and 1H-1H double quantum filtered correlated spectroscopy, rotating frame nuclear Overhauser effect spectroscopy, J-resolved 1H as well as 1H-13C correlation NMR spectra . Geometry of the polyene chromophore was determined as 22E,24E,26E,28Z,30Z,32E,34E. J Antibiot (Tokyo), 1989 Nov, 42(11), 1541 - 6 Novel antifungal antibiotics maniwamycins A and B . II . Structure determination; Takahashi Y et al.; The structures of the new azoxy antibiotics maniwamycins A and B have been determined by means of spectral analyses and chemical studies. J Pharm Pharmacol, 1989 Nov, 41(11), 795 - 6 Transport of cephalosporin antibiotics in rat renal basolateral membranes; Takano M et al.; Transport mechanisms of cephalosporin antibiotics in rat renal basolateral membranes have been studied in isolated membrane vesicles . Uptake of {14C}p-aminohippurate, a typical organic anion, by basolateral membrane vesicles was enhanced when membrane vesicles were preloaded with unlabelled p-aminohippurate (counter-transport) . Cephalosporins such as cephradine, cephalexin, and cefazolin inhibited the counter-transport of {14C}p-aminohippurate, as did unlabelled p-aminohippurate and probenecid . In contrast, cephalexin did not affect the uptake of {3H}tetraethylammonium, an organic cation, by basolateral membrane vesicles . These results suggest that most cephalosporins are transported via organic anion transport systems in rat renal basolateral membranes. Biochem Pharmacol, 1989 Nov 1, 38(21), 3867 - 72 Selective membrane toxicity of aminoglycoside antibiotics in membrane vesicles isolated from proximal renal tubules of the rat; Amacher DE et al.; A considerable body of evidence suggests that the nephrotoxic potential of aminoglycoside antibiotics may be associated with the degree of membrane binding and subsequent membrane damage in the renal tubules . In this study, we isolated functional basolateral and luminal membrane vesicles from rat renal cortex, incubated each membrane type in the presence of 1 mM concentrations of either neomycin, netilmicin, gentamicin, hydroxygentamicin, or amikacin, and monitored the activities of the marker enzymes alkaline phosphatase (ALP) and lambda-glutamyltransferase (GGT) (luminal) or ouabain-sensitive Na+,K+-ATPase (basolateral) to determine if there were any selective drug-related alterations of enzyme activities . While none of the five aminoglycosides had any substantive effect upon enzyme activities of luminal vesicles, all five drugs inhibited the basolateral marker enzyme . Neomycin produced the greatest inhibition, hydroxygentamicin and amikacin the least, and gentamicin and netilmicin were intermediate in the inhibition of the enzyme . These results are in accordance with the known relative nephrotoxicity of these same drugs and indicate the usefulness of isolated renal membrane vesicles for in vitro toxicological studies of novel aminoglycosides. Eur J Clin Microbiol Infect Dis, 1989 Nov, 8(11), 943 - 50 Structure, biochemistry and mechanism of action of glycopeptide antibiotics; Reynolds PE; Glycopeptide antibiotics, including vancomycin and teicoplanin, are large, rigid molecules that inhibit a late stage in bacterial cell wall peptidoglycan synthesis . The three-dimensional structure contains a cleft into which peptides of highly specific configuration (L-aa-D-aa-D-aa) can fit: such sequences are found only in bacterial cell walls, hence glycopeptides are selectively toxic . Glycopeptides interact with peptides of this conformation by hydrogen bonding, forming stable complexes . As a result of binding to L-aa-D-Ala-D-Ala groups in wall intermediates, glycopeptides inhibit, apparently by steric hindrance, the formation of the backbone glycan chains (catalysed by peptidoglycan polymerase) from the simple wall subunits as they are extruded through the cytoplasmic membrane . The subsequent transpeptidation reaction that imparts rigidity to the cell wall is also thus inhibited . This unique mechanism of action, involving binding of the bulky inhibitor to the substrate outside the membrane so that the active sites of two enzymes cannot align themselves correctly, renders the acquisition of resistance to the glycopeptide antibiotics more difficult than that to the majority of the other antibiotic groups. Antibiot Khimioter, 1989 Nov, 34(11), 811 - 3 {Mutagenic effect of mitomycin C on different strains of oleandomycin producer Streptomyces antibioticus}; Tankevich ME et al.; Mitomycin C, a DNA-tropic antibiotic, was shown to have a lethal effect on spore sprouts of two strains of Streptomyces antibioticus, an organism producing oleandomycin . When the time of exposure to the antibiotic increased there was an almost equal decrease in the survival rate . The mutagen action on the morphological variation and antibiotic production of the two closely related strains were diverse due to their genetic differences . The strain isolated after the culture treatment with a chemical mutagen and subjected to a more prolonged maintaining selection showed lower variation with respect to its colony morphology . The other strain isolated after treatment of the culture with high concentrations of its own antibiotic showed lower variation with respect to its antibiotic production property . The shift in the antibiotic production in the direction of the low active variants was characteristic of the both highly productive strains. Vopr Virusol, 1989 Nov-Dec, 34(6), 724 - 7 {Structure-activity relation for rhodomycin-type antibiotics and the inhibition kinetics of single-stranded and double-stranded DNA- and RNA-viruses}; Korting HJ et al.; The antiviral activity of anthracycline antibiotics of rhodomycin group was investigated by two independent methods which determined the infectious units or antigenicity of the viruses . The action of rhodomycin depended on the structure, number, and position of amino sugar in aglycon . The antiviral activity was found to increase in serial order: iremycin--adriamycin--daunomycin--alpha-rubicin--beta-rhodom ycin-- violamycin B I complex by inhibition kinetics determined with adenovirus. Mutagenesis, 1989 Nov, 4(6), 439 - 45 In vitro and in vivo cytogenetic studies of three beta-lactam antibiotics (penicillin VK, ampicillin and carbenicillin); Stemp G et al.; The in vitro and in vivo clastogenic potential of three beta-lactam antibiotics, ampicillin, carbenicillin and penicillin VK, was investigated using cultured human lymphocytes and the rat micronucleus test . Neither ampicillin nor carbenicillin induced significant increases in chromosome damage in vitro up to test concentrations of 10 mg/ml . These results contrast with other published studies on these compounds . Both drugs were also inactive in vivo in the rat micronucleus test, using single- or double-dosing regimens (ampicillin 5 g/kg orally; carbenicillin 500 mg/kg i.m., either dosed once 30 h before marrow preparation, or dosed twice 48 and 24 h before marrow preparation) . In vitro, penicillin VK induced a dose-related increase in chromosome and chromatid gaps and breaks, down to concentrations of 1.25 mg/ml . It is likely that the increase in aberration frequency was partly the result of exposing the cells to increased K+ ion concentration, as similar results were obtained when potassium chloride was evaluated over the same molar concentration range . However, the occurrence of 'ion-mediated' clastogenic effects as reported by other workers, does not fully account for the positive effects obtained with this compound, as clastogenic effects were also observed with penicillin V in this test system at similar test concentrations . It is known that exposure of mammalian cells to extremely high concentrations of beta-lactams can affect DNA polymerase alpha activity . An inhibitory effect upon DNA polymerase alpha resulting in a breakdown in the structural integrity of the chromosomes, is suggested as an additional mechanism of action for penicillin VK.(ABSTRACT TRUNCATED AT 250 WORDS) Eur J Pediatr, 1989 Nov, 149(2), 126 - 9 Fat absorption in premature infants: the effect of lard and antibiotics; Verkade HJ et al.; Fat absorption of an adapted cow's milk formula was studied in a randomized controlled trial involving two groups of 18 premature infants (mean gestational age +/- SD: 33.0 +/- 2.9 weeks, range 26.5-37.5 weeks) . The triglyceride configuration was modified by the use of lard . This modification did not improve the absorption of fat or energy . Also no difference in serum concentrations of cholesterol and triglycerides was found . Growth velocity during the study was similar in both groups . Detailed analysis of the data revealed that in infants who received (parenterally) antibiotics (mainly ampicillin and netilmicin) a higher coefficient of fat absorption (+20%, P less than 0.01) and of energy absorption (+8%, P = 0.03) was found . Based on these results, we find no support for the use of lard in adapted cow's milk infant formulas to improve fat absorption . In studies of fat and energy absorption the effects of antibiotics have to be taken into account. BMJ, 1989 Oct 21, 299(6706), 1003 - 6 Reducing the incidence of infection after caesarean section: implications of prophylaxis with antibiotics for hospital resources; Mugford M et al.; OBJECTIVES--To estimate the cost effectiveness of giving prophylactic antibiotics routinely to reduce the incidence of wound infection after caesarean section . DESIGN--Estimation of cost effectiveness was based, firstly, on a retrospective overview of 58 controlled trials and, secondly, on evidence about costs derived from data and observations of practice . SETTING--Trials included in the overview were from obstetric units in several different countries, including the United Kingdom . The costing study was based on data referring to the John Radcliffe Maternity Hospital, Oxford . SUBJECTS--A total of 7777 women were included in the 58 controlled trials comparing the effects of giving routine prophylactic antibiotics at caesarean section with either treatment with a placebo or no treatment . Cost estimates were based on data on 486 women who had caesarean sections between January and September 1987 . MAIN OUTCOME MEASURE--Cost effectiveness of prophylaxis with antibiotics . RESULTS--The odds of wound infection are likely to be reduced by between about 50 and 70% by giving antibiotics routinely at caesarean section . Forty one (8.4%) women who had caesarean section were coded by the Oxford obstetric data system as having developed wound infection . The additional average cost of hospital postnatal care for women with wound infection (compared with women who had had caesarean section and no wound infection) was estimated to be 716 pounds; introducing routine prophylaxis with antibiotics would reduce average costs of postnatal care by between 1300 pounds and 3900/100 pounds caesarean sections (at 1988 prices), depending on the cost of the antibiotic used and its effectiveness . CONCLUSIONS--The results suggest that giving antibiotics routinely at caesarean section will not only reduce rates of infection after caesarean section but also reduce costs. Proc Natl Acad Sci U S A, 1989 Oct, 86(20), 7672 - 6 Nucleotide-specific cleavage and minor-groove interaction of DNA with esperamicin antitumor antibiotics; Sugiura Y et al.; The cleavage of DNA by esperamicin is greatly accelerated in the presence of thiol compounds . Oxygen and active oxygen-radical scavengers have no significant influence upon DNA strand breakage by esperamicin . The preferential cutting sites of esperamicin are at thymidylate residues, and the frequency of bases attacked (T greater than C greater than A greater than G) is different from that of calicheamicin (C much greater than T greater than A = G), neocarzinostatin (T greater than A greater than C greater than G), or bleomycin (C greater than T greater than A greater than G) . Esperamicin preferentially attacks at T and C bases in oligopyrimidine sequences such as 5'-CTC-3', 5'-TTC-3', and 5'-TTT-3' . In contrast to the preferred sites of cleavage by bleomycin, 5'-GT-3' and 5'-GC-3', the preferred sites of esperamicin-mediated DNA degradation are 5'-TG-3' and 5'-CG-3' sequences . The nucleotide-specific cleavage mode of esperamicin is significantly affected by pretreatment of DNA with netropsin and distamycin A, suggesting that interaction of esperamicin occurs through the minor groove of B-DNA . This is further supported by the asymmetric cleavage pattern to the 3' side on the opposite strand of the DNA . The roles of the fucose-anthranilate moiety and the trisaccharide side chain of esperamicin in DNA binding and base recognition are discussed. J Trauma, 1989 Oct, 29(10), 1356 - 61 Prophylactic antibiotics in trauma: the hazards of underdosing; Ericsson CD et al.; Prophylactic antibiotic regimens in trauma patients may be significantly altered by large fluid shifts and hyperdynamic physiologic responses . We prospectively studied prophylactic amikacin and clindamycin in 150 abdominal trauma patients requiring laparotomy, analyzing the effects of duration of coverage, dosing interval, and dose . No difference in infection rates was noted when 72-hour coverage was compared with 24-hour coverage (19% vs . 21%) . Clindamycin dosed at 1,200 mg every 12 hours achieved acceptable serum concentrations; infection rates were not significantly higher than seen with 600 mg every 6 hours (21% vs . 12%, p greater than 0.05) . High-dose (11 mg/kg) amikacin reduced infection rates in patients with high blood loss (p less than 0.025), high Injury Severity Scores (p less than 0.025), and no colon penetration (p less than 0.005) . These data suggest that high doses are more effective than long courses of antibiotics in reducing infections in trauma patients undergoing laparotomy. J Antibiot (Tokyo), 1989 Oct, 42(10), 1482 - 8 Urdamycins, new angucycline antibiotics from Streptomyces fradiae . VI . Structure elucidation and biosynthetic investigations on urdamycin H; Rohr J; A new angucycline antibiotic has been discovered as a small side product of Streptomyces fradiae (strain Tu 2717), the producer of the urdamycin complex, during screening for biosynthetic relatives of urdamycins C and D . The structure was elucidated after isolation, via strain selection, of a mutant of S . fradiae that produces this new congener in larger amounts . The structure includes a new chromophore containing aglycone that has not been found before among the angucyclines nor as a natural product generally . In urdamycin H (1) the angucycline four-ring system is enlarged by a (p-OH-phenyl)furan moiety and is closely related to urdamycin C (2) . The structure was elucidated by comparison of the physico-chemical data with those of known urdamycins, especially with those of urdamycin C (2), and was confirmed by intensive 2D NMR analysis . Biosynthetic studies showed that tyrosine and not the smaller p-OH-phenylglycine is the precursor of the (p-OH-phenyl)furan moiety. Am J Surg, 1989 Oct, 158(4), 324 - 7 Efficacy of an antibiotic mouthwash in contaminated head and neck surgery; Jones TR et al.; Twelve head and neck cancer patients scheduled to undergo an operation contaminated by entrance into the upper aerodigestive tract were enrolled in a prospective, randomized, double-blinded study to evaluate the efficacy of a preoperative antibiotic mouthwash in reducing oral cavity quantitative bacterial counts and the incidence of postoperative wound infections . The group who received the antibiotic mouthwash had a large reduction in the bacterial counts, whereas the group who received the placebo mouthwash had an increase in the bacterial counts (p = 0.024) . None of the patients who received the antibiotic mouthwash had postoperative complications; two of the five patients who received the placebo mouthwash had postoperative complications. Am Fam Physician, 1989 Oct, 40(4), 157 - 62 Outpatient intravenous antibiotic therapy; Brown RB et al.; Outpatient intravenous antibiotic therapy is a cost-effective modality to shorten hospital stays and provide continued care to patients with infections . The recent availability of tamper-proof pumps that can deliver multiple antibiotics on independently timed regimens will further expand the use of home intravenous antibiotics . Problems with reimbursement remain, and new classes of oral antibiotics may provide alternatives to parenteral medications. Minerva Urol Nefrol, 1989 Oct-Dec, 41(4), 271 - 3 {Early antibiotic therapy following urodynamic examination . Results of a randomized, controlled study}; Tosto A et al.; Forty-three young men from the Italian army underwent urodynamic tests following the diagnosis of enuresis . Of these, 37 were included in an assessment trial to define the rationale for early anti-bacterial therapy following the test . The subjects were subdivided into two groups: one group received 500 mg Cinoxacin b.i.d . for 5 days, and the other group was not treated . The comparison of results revealed a high incidence of irritative disorders in both groups (78.9% of treated subjects and 88.9% of untreated subjects) but the most significant complications were observed in the untreated group (feveret in 27.7% and one case of septic fever) . Early anti-bacterial therapy following standard urodynamic tests therefore seems to be a ration tool in urological practice. Rev Fr Gynecol Obstet, 1989 Oct, 84(10), 699 - 703 {Treatment of upper genital infections in women . Multicenter study of the comparative efficacy and tolerance of an amoxicillin-clavulanic acid combination and of a triple antibiotic combination}; Buisson P et al.; Eighty-two patients with laparoscopically confirmed salpingitis were randomly divided into two groups in a multicentre and prospective trial . Single drug therapy with the amoxicillin-clavulanic acid combination was used in 42 patients (group A) . The other 40 patients were given a combination of penicillin, aminoside and metronidazole (group B) . For each case a secondary prescription for a tetracycline was discussed . Clinical results were comparable in both groups: sooner (at the end of the hospitalization period) in group A: 10 cured, 30 improved and 2 failures against 9 cured, 30 improved in group B . Later (evaluation after 5 to 8 weeks) a relapse was noted in five patients in group A and included one case of angioedema in group B . It is concluded that amoxicillin-clavulanic acid combination is a satisfactory alternative to the penicillin-aminoside-metronidazole combination, especially as it is simpler to use. Indian J Biochem Biophys, 1989 Oct, 26(5), 293 - 5 Effect of anthracycline antibiotics on in vitro transcription of chromatin in a Sarcoma-180 whole cell extract; Panda CK et al.; A soluble extract capable of transcribing Sarcoma-180 chromatin and DNA in a cell-free transcription system was prepared from Sarcoma-180 mouse ascites tumour cells . Incorporation of {3H}UTP into trichloroacetic acid-precipitable fraction is (i) reduced by 50% on removing DNase I hypersensitive sites of chromatin and (ii) inhibited by DNA binding antitumour anthracyclines, suggesting that this cell-free assay represents true transcription of active genes of Sarcoma-180 chromatin . Preparation of this soluble extract from mouse ascites tumour cells thus presents a very convenient way of studying cell-free transcription of active genes of chromatin and effect of antitumour agents on chromatin transcription. J Dent, 1989 Oct, 17(5), 241 - 5 Retrograde root filling using antibiotic-containing, radiopaque, bone cement; High AS et al.; An investigation is reported on the in-vitro behaviour, characteristics and properties of three gentamicin-containing radiopaque bone cements that are considered to be promising retrograde root-filling materials . Three commercially available cements, CMW-1G, CMW-3G and Palacos R with gentamicin were studied with regard to bacteriocidal properties, tissue compatibility in cell culture, and ability to seal tooth cavities as evidenced by dye diffusion . Results were compared and contrasted with those obtained with an amalgam . The antibiotic-containing cements investigated are considered to have some distinct advantages over amalgam when used as retrograde root-filling materials in vitro . Amalgam was found to have poor bacteriocidal properties and poor tissue compatibility but slightly better apical sealing abilities than the cements . No apparent drawbacks were found with the cements. J Neurosci Res, 1989 Oct, 24(2), 338 - 46 Aminoglycoside antibiotics impair calcium entry but not viability and motility in isolated cochlear outer hair cells; Dulon D et al.; Cochlear outer hair cells have been well established as primary targets of the ototoxic actions of aminoglycoside antibiotics . These cells, isolated from the guinea pig cochlea and maintained in short-term culture, were used as a model for evaluating the acute effects of gentamicin on cell viability, depolarization-induced transmembrane calcium flux, and depolarization-induced motile responses . On the basis of morphology and fluorochromasia, the presence of extracellular gentamicin as high as 5 mM did not affect the viability of the cells for up to 6 hr, the longest time tested . Viable cells showed binding of fluorescently tagged gentamicin to their base but excluded the drug from their cytoplasm . In response to {K+}-depolarization, intracellular calcium levels (monitored with the fluorescent calcium-sensitive dye fluo-3) increased from a resting value of 218 +/- 102 nM to 2,018 +/- 1,077 nM concomitant with a cell shortening of 0.7% +/- 1.3% . The depolarization-induced calcium increase was apparently caused by calcium entry into the cell as it was inhibited by the calcium-channel blocker methoxyverapamil and prevented in the absence of extracellular calcium . Both gentamicin and neomycin blocked the {K+}-induced calcium increase at an IC50 of 50 microM . Despite the inhibition of calcium entry the ability of the outer hair cells to shorten under {K+}-depolarization was not impaired; in fact, cell shortening was even more pronounced in the absence of calcium influx (2.6% +/- 1.4%) . This argues effectively against the existence of a calcium-dependent actomyosin-mediated component in {K+}-induced shape changes.(ABSTRACT TRUNCATED AT 250 WORDS) J Am Podiatr Med Assoc, 1989 Oct, 79(10), 500 - 4 Adverse effects of antibiotics; Brown RB et al.; Adverse reactions to antibiotics comprise a number of classes of reactions, including toxicity, side effects, and allergy . Each one of these differs in its implication for treatment of the patient . The authors discuss some of the more common and unusual reactions to antibiotics frequently used in the practice of podiatric medicine. Cancer Biochem Biophys, 1989 Oct, 10(4), 289 - 98 Effect of the superoxide dismutase inhibitor, diethyldithiocarbamate, on the cytotoxicity of mitomycin antibiotics; Pritsos CA et al.; Mitomycin C (MC) and its structural analogs porfiromycin (PM), BMY-25282 and BL-6783 are toxic to EMT6 cells under aerobic and hypoxic conditions . The mitomycin antibiotics are hypothesized to exert cytotoxicity under hypoxic conditions by cross-linking DNA following reductive activation, while aerobic cytotoxicity may involve DNA cross-linking by these agents and/or damage due to the generation of oxygen radicals . Previous findings (Pritsos and Sartorelli, 1986) indicated that the rank order of cytotoxicity for a series of mitomycins was the same as the rank order for the rate of oxygen consumption induced by these agents . As an additional approach to explore the role of oxygen radicals in the aerobic cytotoxicity of the four agents studied, EMT6 cells were treated with the mitomycins in the presence of the superoxide dismutase inhibitor diethyldithiocarbamate (DETC) . DETC, which decreased superoxide dismutase activity in EMT6 cells, increased the cytotoxicity of BMY-25282 and BL-6783 by half an order of magnitude, but did not affect the toxicity of PM or MC to these cells . DNA cross-links, a proposed cytotoxic lesion induced by BMY-25282, however, were not detectably increased in EMT6 cells exposed to this agent in the presence of DETC in spite of the large increase in cytotoxicity under these treatment conditions . No single strand breaks were detected in cells exposed to either BMY-25282 or BMY-25282 plus DETC . The findings support the concept that oxygen radicals may have a role in the aerobic cytotoxicity of some of the mitomycin antibiotics, and that the lesions responsible for cytotoxicity produced by oxygen radicals may not reside entirely at the level of DNA. Immunobiology, 1989 Oct, 179(4-5), 445 - 55 Studies on the immunomodulatory effects of anthracycline antibiotics in mice: effects on immune responses and graft immunogenicity; Eckert R et al.; The immunomodulatory effects of adriamycin, a clinically used tumor antibiotic, were studied . A 5-day course of adriamycin therapy in mice led to a suppression of the primary but not of the secondary humoral response to sheep erythrocytes without significant alterations in peripheral blood leukocyte subsets or lymphocyte subpopulations in the spleen . The delayed type hypersensitivity (DTH) response to ovalbumin or alloantigens was not inhibited . Adriamycin-treated spleen cells were unable to stimulate an allogeneic mixed leukocyte reaction, which shows that antigen presentation is inhibited by this drug . Adriamycin-treated murine skin grafts show a prolonged survival after allotransplantation despite their unimpaired ability to induce DTH . The possible cellular mechanisms of these effects and clinical relevance of adriamycin are discussed. J Antimicrob Chemother, 1989 Oct, 24(4), 551 - 9 Decrease in a constitutive form of cytochrome P-450 by macrolide antibiotics; Miura T et al.; The effects of administration of macrolide antibiotics on cytochrome P-450 in liver microsomes of male rats were investigated . The macrolides tested were those with a 14-membered ring such as oleandomycin, troleandomycin, erythromycin and erythromycin estolate, and those with a 16-membered ring such as rokitamycin, leucomycin and josamycin . Cytochrome P-450-metabolite complex was detected with oleandomycin, troleandomycin, erythromycin and erythromycin estolate, whereas no such effect was observed with rokitamycin, leucomycin and josamycin . The content of uncomplexed cytochrome P-450 in liver microsomes remained unchanged with rokitamycin, leucomycin and josamycin, decreased with troleandomycin and oleandomycin, and increased with erythromycin and erythromycin estolate, indicating that oleandomycin, troleandomycin, erythromycin and erythromycin estolate also affect the amounts of other forms of cytochrome P-450 . The administration of oleandomycin, troleandomycin, erythromycin and erythromycin estolate resulted in a dramatic decrease in the activities of testosterone 2 alpha- and 16 alpha-hydroxylases in liver microsomes . Supporting these results, a marked decrease (more than 75%) in the content of P-450-male, a major constitutive form of cytochrome P-450 in male rats, was noted with oleandomycin, troleandomycin, erythromycin and erythromycin estolate, while the decrease was rather small with rokitamycin and leucomycin . We conclude that the administration of the 14-membered ring macrolides may affect drug and steroid metabolism not only by formation of P-450-metabolite complex but also by decrease in the content of P-450-male. J Antimicrob Chemother, 1989 Oct, 24(4), 485 - 507 The molecular basis of the inhibitory activities of type A and type B synergimycins and related antibiotics on ribosomes; Di Giambattista M et al.; Synergimycins A and B act synergistically in vivo; the mixture of the two compounds is more powerful than the individual components and their combined action is irreversible . Type A (virginiamycin M, VM-like) components inactivate the donor and acceptor sites of peptidyltransferase, thus interfering with the corresponding functions of the enzyme . They block two of the peptide chain elongation steps: aminoacyl-tRNA (AA-tRNA) binding to the A site of ribosomes, and peptide bond formation with peptidyl-tRNA (pep-tRNA) at the P site . A tight (non-exchangeable) linkage of tRNA derivatives with the two ribosomal sites requires a stable interaction of their aminoacyl component with peptidyltransferase . Such interaction is prevented by VM, hence the release of AA-tRNA from the A site and of pep-tRNA from the P site upon translocation; ultracentrifugally unstable particles (60S) are thus formed . A new model for peptidyltransferase has been proposed, to account for the interference of VM with the two sites of the enzyme . The action of this antibiotic is partly due to its presence on the ribosome, and partly to the conformational alterations triggered by its binding . Type B synergimycins (VS-like) and the related 14-membered macrolides (erythromycin) have a more complex action, as revealed by copolymer-based models of cell-free protein synthesis . These antibiotics produce an inhibition of peptide bond formation, and a release of incomplete peptide chains, which processes are both template-dependent (i.e . linked to the polymerization of basic amino acids and proline) . The functional interference of VS with peptidyltransferase is explained by the location of the corresponding binding site at the base of the central protuberance of 50S subunits . When ribosome.VS complexes are incubated with erythromycin, the former antibiotic is replaced by the latter; such a replacement does not occur in the presence of VM, which reduces ribosome affinity for macrolides and increases that for type B synergimycins . A study of these complex ribosomal interactions by stopped-flow spectrofluorimetry had allowed a mapping of the binding sites for the MLS antibiotics (macrolides, lincosamides, type B synergimycins) within the peptidyltransferase domain . The active component of these binding sites is represented by segments (loop V and domain II) of 23S rRNA, as indicated by protection and mutation mapping experiments, L proteins increasing the affinity of fixation and its specificity. Biochim Biophys Acta, 1989 Sep 21, 1009(1), 39 - 46 Analysis of the reversible binding of virginiamycin M to ribosome and particle functions after removal of the antibiotic; Nyssen E et al.; Type A synergimycins (VM) were shown to act catalytically and to induce two ribosomal alterations: (a) inability to promote polypeptide synthesis; (b) high-affinity binding of type B synergimycins (VS) . A claim for irreversible binding of type A synergimycins to ribosomes has promoted the present reinvestigation . Submission of ribosomes from VM-treated bacteria to a purification procedure (supposed to remove the drug, according to a low association constant previously reported) yielded particles still holding residual VM . The formation of VM.ribosome complexes, more stable than previously inferred but without covalent linkage, was deduced from the extractability of complexed VM by organic solvents . Moreover, incubation of these complexes with increasing amounts of anti-VM immunoglobulins progressively restored ribosome activity in protein synthesis . Binding of VS to ribosomes, by fluorimetric titrations in the presence of substoichiometric concentrations of VM, was incompatible with catalytic action of type A synergimycins . Ribosomes from VM-treated bacteria displayed also a higher affinity for VS than did control ribosomes . This property did not disappear when ribosome.VM complexes were incubated with anti-VM IgG, nor when VM-IgG complexes were withdrawn from the reaction mixture by protein A-agarose binding . We can conclude that VM binding produces: (1) an inhibition of ribosome-promoted peptide bond formation, which occurs only in the presence of the drug; and (2) an increase of ribosome affinity for VS, which lasts after VM removal . The linkage of this drug with ribosomes is tight but reversible and its action is stoichiometric. Vet Rec, 1989 Sep 9, 125(11), 301 - 3 Antibiotic persistence and tolerance in the lactating goat following intramammary therapy; Buswell JF et al.; Due to the impact of the dairy quota system, the commercial use of goats for the production of milk and associated products is attractive to farmers diversifying their dairy interest . Intensification of milking and the expansion of herds will inevitably increase the incidence of caprine mastitis . The pharmaceutical industry and the veterinary surgeon will be required to provide data and advice upon the performance of currently available bovine intramammary products when used in the goat . This study produced evidence that one available bovine intramammary product, when infused into the glands of milking goats, produced a withholding time approximately double that defined for the cow . Following a course of infusions after three successive milkings, milk was not available for human consumption or for the production of cheese and yoghurt until 112 hours after the final infusion . This situation is likely to be representative of that which will occur for other currently available bovine intramammaries when prescribed in the goat. J Antibiot (Tokyo), 1989 Sep, 42(9), 1370 - 8 Studies on a new herbicidal antibiotic, homoalanosine; Fushimi S et al.; Homoalanosine having a herbicidal activity was isolated from the culture filtrate of a soil isolate SC-1688 which was classified as Streptomyces galilaeus . The chemical structure of homoalanosine was determined to be L-2-amino-4-nitrosohydroxyaminobutyric acid by analyses of spectral and biological data . The antibiotic has high herbicidal activity at low concentrations against especially common cocklebur and ladysthumb among the tested weeds and crops . Foliar application of this antibiotic inhibited the growth of roots and buds . This result indicated that homoalanosine had a systemic herbicidal activity. J Antibiot (Tokyo), 1989 Sep, 42(9), 1339 - 43 Novel antitumor antibiotic phospholine . 2 . Structure determination; Ozasa T et al.; Phospholine, an antitumor antibiotic, has the molecular formula of C25H40NO8P and possesses a delta-lactone and a phosphoric acid ester as functional groups . Its structure was determined based on interpretation of fast atom bombardment MS, 1H NMR, 13C NMR, 1H-1H correlation spectroscopy (COSY), 13C-1H COSY, heteronuclear multiple bond correlation spectroscopy, elemental analysis and chemical modifications. Am J Obstet Gynecol, 1989 Sep, 161(3), 568 - 72 Short course of antibiotic therapy in treatment of postpartum endomyometritis; Morales WJ et al.; To evaluate the safety and efficacy of an abbreviated course of antibiotic therapy in postpartum endomyometritis, 109 patients with endomyometritis were randomized to three study groups . All were treated with clindamycin and tobramycin until afebrility and clinical signs of disease were absent . Patients in group I received antibiotics for greater than or equal to 24 hours, group II received therapy for greater than or equal to 48 hours, and group III received antibiotic therapy for greater than or equal to 48 hours that preceded a 7-day course of oral Augmentin . The groups were similar in size and in demographic and clinical parameters . Two patients from each group required a third antibiotic, and no patient required rehospitalization . Group III required more days of antibiotic therapy than did group I, 2.9 versus 2.1 days (p less than 0.01), and cost $412.00 more per patient . This data strongly suggest that a short course of antibiotic therapy is efficacious and safe and would result in substantial monetary savings. Spine, 1989 Sep, 14(9), 1025 - 32 Iatrogenic discitis: the role of intravenous antibiotics in prevention and treatment . An experimental study; Fraser RD et al.; The role of antibiotics in the treatment of iatrogenic discitis remains controversial . This study was carried out to assess the ability of cephazolin (a first-generation cephalosporin) to penetrate the intervertebral disc and to establish the role of intravenous antibiotics in the prevention and treatment of iatrogenic discitis . Six sheep had 1 g of intravenous antibiotic administered between 30 minutes and 120 minutes before being killed . Two adjacent lumbar intervertebral discs were harvested and assayed for antibiotic concentration . Cephazolin could only be detected in the animals killed at 30 minutes . Intravenous cephazolin was administered 30 minutes before bacterial inoculation in 46 discs of nine sheep . In five animals, the bacterial suspension contained radiographic contrast and, in four sheep, reconstituted chymopapain . No evidence of discitis was found at any level at death . Eight sheep were treated with intravenous cephazolin commencing 1, 2, or 3 weeks after bacterial intradiscal inoculation and for periods of up to 21 days . All discs developed discitis, and the lesions appeared to be similar, irrespective of time between inoculation and the commencement, duration, and dosage of antibiotic therapy . Our study supports the use of a suitable broad-spectrum antibiotic during any surgical procedure that invades the intervertebral disc . Antibiotics, however, are unable to arrest the progression of discitis once it is established Genetika, 1989 Sep, 25(9), 1705 - 7 {Resistance of yeasts to polyene antibiotics}; Kamilova TA et al.; The strains of Saccharomyces cerevisiae yeast with mutations in two genes NYS3 NYS4 were obtained by tetrad analysis . Sterol fraction of these mutants contains two sterols: ergosta-7-en-3 beta-ol (fungisterol) and ergosta-7,24-dien-3 beta-ol (episterol) . The findings allowed to testify the sequence of the ergosterol biosynthesis reactions . Dehydrogenization of the sterol nucleus in C5(6) which is controlled by gene NYS3 occurs simultaneously with the introduction of double bond in C22(23) site of the side chain regulated by gene NYS4. Kardiologiia, 1989 Sep, 29(9), 64 - 7 {Comparative evaluation of the cardiotoxic effects of antineoplastic antibiotics adriamycin and pharmorubicin}; Valvere VIu et al.; Thirty patients with Grade III breast cancer, a locally common form, were examined to compare the magnitude of the cardiotoxic effects displayed by the antitumor anthracyclic antibiotics adriamycin (15 patients) and pharmorubicin (15 patients) . Clinical symptoms of cardiotoxicity developed in 13.3% of the pharmorubicin-treated and in 40% of the adriamycin-treated patients . Among the noninvasive techniques, electrocardiography turned out to be more informative, which enabled the signs of myocardial dystrophy and cardiac arrhythmias to be identified in 20 and 40% on pharmorubicin and adriamycin, respectively . Poly- and echocardiography proved to be less informative than it was shown by the data available in the literature, which is associated with the use of relatively small total doses of anthracycline in our investigations. EMBO J, 1989 Sep, 8(9), 2727 - 36 Analysis of the nucleotide sequence of the Streptomyces glaucescens tcmI genes provides key information about the enzymology of polyketide antibiotic biosynthesis; Bibb MJ et al.; Key information about the biosynthesis of polyketide metabolites has been uncovered by sequence analysis of the tetracenomycin C polyketide synthase genes (tcml) from Streptomyces glaucescens GLA.0 . The sequence data revealed the presence of three complete open reading frames (ORFs) . ORF1 and ORF2 appear to be translationally coupled and would encode proteins containing 426 and 405 amino acids, respectively . The two deduced proteins are homologous to known beta-ketoacyl synthases . ORF3 begins 70 nucleotides after the stop codon of ORF2 and would code for an 83 amino acid protein with a strong resemblance to known bacterial, animal and plant acyl-carrier proteins (ACP) . The presence of an ACP gene within the tcm gene cluster suggests that different ACPs are used in fatty acid and polyketide biosynthesis in Streptomyces . We conclude from these data and earlier information that polyketide biosynthesis in S . glaucescens, and most likely in other bacteria, involves a multienzyme complex consisting of at least five types of enzymes: acylCoA transferases that load the acyl and 2-carboxyacyl precursors onto the ACP; a beta-ketoacyl synthase that, along with the acylated ACP, forms the poly-beta-ketoacyl intermediates; a poly-beta-ketone cyclase that forms carbocyclic structures from the latter intermediates; a beta-ketoacyl oxidoreductase that forms beta-hydroxyacyl intermediates or reduces ketone groups in fully formed polyketides; and a thioesterase that releases the assembled polyketide from the enzyme. J Antimicrob Chemother, 1989 Sep, 24(3), 407 - 13 Pharmacokinetic evaluation of beta-lactam antibiotics; Derendorf H; A simple method is proposed to predict free tissue concentrations of beta-lactam antibiotics from their plasma concentrations after iv bolus injection . During the elimination phase these free tissue concentrations exceed corresponding free plasma concentrations by a constant compound specific factor . This factor can be calculated from the different volumes of distribution (Vc, Vdss and Vdarea) and the plasma protein binding . Calculation of free tissue concentrations allows more secure interpretation of pharmacokinetic data with respect to in-vitro MICs for the comparison of different antibiotics or of the same antibiotic in different patient populations. Infect Dis Clin North Am, 1989 Sep, 3(3), 507 - 16 Antibiotic use in the elderly . A selective review; Gleckman RA; There are unique challenges for the physician who prescribes an antibiotic to an elderly patient . Advanced age is associated with physiological alterations and a reduction in the excretion of numerous compounds . Mental and physical illness in aged patients will impair unsupervised drug compliance . Antibiotic-related adverse events and antibiotic-associated drug interactions pose a threat to life and impede the desired therapeutic outcome. Actual Odontostomatol (Paris), 1989 Sep, 43(167), 433 - 48 {Pharmacokinetics and antibiotic therapy of the child}; Sixou JL et al.; Pharmacokinetics is too often unknown while ordering antibiotics, particularly to children . The aim of that paper is to recall the pharmacokinetic characteristics of the most ordered families in pediatric dentistry: penicillin A and macrolides, as well as the modifications peculiar to children, due to pathology, or subsequent to drug interactions. Ceylon Med J, 1989 Sep, 34(3), 131 - 3 Halitosis and abuse of antibiotics . Report of a case; Ogunwande SA; A case of halitosis caused by the abuse of antibiotics is presented . The abuse of tetracycline resulted in a black hairy tongue and halitosis in this patient . Periodontal therapy and the withdrawal of tetracycline corrected these problems . This is the first patient with halitosis due to abuse of tetracycline seen in our clinic. Vestn Khir Im I I Grek, 1989 Sep, 143(9), 40 - 4 {Endolymphatic administration of antibiotics in the complex treatment of postoperative abscesses in the abdominal cavity}; Zubarev PN et al.; The endolymphatic administration of solutions of antibiotics in complex treatment of patients with intraperitoneal postoperative abscesses resulted in more rapid attenuation of intoxication, improvement of the general state of the patients and their recovery . No complications of the treatment were noted. Postgrad Med J, 1989 Sep, 65(767), 650 - 2 Attitudes of hospital doctors in Wales to use of intravenous fluids and antibiotics in the terminally ill; Marin PP et al.; Decisions concerning the use of intravenous fluids and antibiotics in terminally ill patients are regularly made by hospital doctors, but there is little record of staff attitudes and current practice in Britain . A questionnaire was therefore distributed to 833 Welsh hospital doctors, citing the case of a hypothetical terminally ill patient and asking questions about medical management . Of the 448 (54%) doctors who replied, 346 (77%) had managed a similar patient recently . Intravenous fluids would be administered by 238 (53%), with 206 of these (87%) resiting the cannula as required and 62 (26%) resorting to a central venous line if there was no alternative . With increasing age and seniority doctors become conservative in their approach . Nearly all claimed that 'ensuring the patient's comfort' was the reason for their decision . Only 72 (16%) would use antibiotics if the patient became pyrexial . The results suggest that British doctors are divided in their approach to the medical management of terminally ill patients and there is a need for greater discussion and training so that all the issues involved are fully appreciated. J Nat Prod, 1989 Sep-Oct, 52(5), 1015 - 21 Biosynthesis of elsamicin A, a novel antitumor antibiotic; Lam KS et al.; The 1H noise-decoupled 13C-nmr spectrum of elsamicin A {1} prepared from the cultures of an unknown actinomycete species (ATCC 39417) supplemented with {1-13C}acetate and {2-13C}acetate showed enrichment of all 19-carbons in the aglycone . In addition, L-{methyl-13C}methionine- and D-{1-13C}glucose-supplemented cultures enriched the carbons of the two methyl groups on the disaccharide moiety and the C-1 carbons of the disaccharide, respectively . The results demonstrated that the aglycone of elsamicin A is derived entirely from acetate and the disaccharide portion is biosynthesized from two units of glucose and methionine. Vestn Otorinolaringol, 1989 Sep-Oct, (5), 15 - 20 {Reasons for the use of mydocalm in the prevention and treatment of antibiotic-induced sensorineural hearing loss}; Lantsov AA et al.; The applicability of mydocalm for the prevention and therapy of hypoacusis caused by kanamycin, an antibiotic of the aminoglycoside series, was investigated in animal (guinea-pig) experiments . The changes in nucleic acids and nuclear size of the spiral organ were used as parameters . Hearing loss as shown by the lack of Preyer's reflex developed in response to kanamycin injected at a dose of 50 mg/kg/day for 14 days . In the spiral organ nuclei of hair cells were in the state of functional shrinkage . The use of mydocalm at a dose of 12 mg/kg in parallel with or after kanamycin injection nuclei of receptor cells did not shrink, Preyer's reflex did not disappear (in the case of parallel administration of mydocalm and kanamycin) or recovered (in the case of mydocalm administration after kanamycin injection) . In summary, mydocalm as a vasoactive and neurotrophic drug can be used for the prophylaxis and therapy of hypoacusis caused by aminoglycoside antibiotics and can be recommended for practical application. J Pharm Sci, 1989 Sep, 78(9), 723 - 7 Characterization of the oral absorption of beta-lactam antibiotics . II . Competitive absorption and peptide carrier specificity; Sinko PJ et al.; The beta-lactam antibiotic oral absorption pathway is studied using a single-pass perfusion technique in the rat small intestine . Beta-lactam antibiotic absorption in the presence of amino acids, small peptides, and other beta-lactams is modeled using a simple competitive inhibition boundary condition at the intestinal wall, with a corrected value for the intestinal wall concentration, Cw, derived from the modified boundary layer analysis . The model-predicted permeability in the presence of an inhibitor is used to characterize the beta-lactam antibiotic intestinal carrier system . Several concentrations of cephalexin, coperfused with a constant concentration of cefadroxil (equal to its Km), showed that the Km of cephalexin approximately doubled from 7.2 (+/- 1.1) to 18.8 (+/- 4.1) mM; Jmax remained unchanged at 9.2 (+/- 1.2) and 11.1 (+/- 2.1) mM; and the carrier permeability, Pc, was reduced by approximately 50% from 1.11 (+/- 0.10) to 0.59 (+/- 0.04), consistent with competitive absorption kinetics . The predicted in situ wall permeability, the mean value of P*w, of beta-lactams perfused in the presence of other beta-lactams was calculated and then compared with experimentally determined values . For cefadroxil, P*w = 0.27 (+/- 0.04), the mean value of P*w = 0.29; for cefatrizine, P*w = 0.67 (+/- 0.09), the mean value of P*w (+/- 0.09), the mean value of P*w = 0.59; and for cephalexin, P*w = 0.56 (+/- 0.05), the mean value of P*w = 0.59.(ABSTRACT TRUNCATED AT 250 WORDS) J Pharm Pharmacol, 1989 Sep, 41(9), 628 - 32 Comparison of transport characteristics of amino beta-lactam antibiotics and dipeptides across rat intestinal brush border membrane; Iseki K et al.; The transport characteristics of amino beta-lactam antibiotics, ampicillin and cephradine, have been examined and compared with that of glycylglycine using brush border membrane vesicles isolated from rat small intestine . The initial rate of glycylglycine uptake was markedly stimulated in the presence of an inward H+ gradient compared with the uptake rates in the absence of an H+ gradient . With the same H+ gradient the stimulation of cephradine uptake was lower and ampicillin uptake was not altered . Cephradine uptake, however, was greater than that of glycylglycine in both vesicular conditions ((pH)i greater than (pH)o and (pH)i = (pH)o) . Inhibitory effects of dipeptides, ampicillin and cephradine on the initial uptake of glycylglycine were also examined . Glycylglycine uptake was significantly decreased in the presence of L-phenylalanylglycine or carnosine . Ampicillin and cephradine did not alter the uptake of glycylglycine . These results suggest that the contribution of the inward H+ gradient to the permeation of ampicillin, cephradine and glycylglycine across the rat small intestinal brush border membranes is different for each of the substances examined. Eur J Clin Microbiol Infect Dis, 1989 Sep, 8(9), 783 - 8 In vitro activity of combinations of beta-lactam antibiotics with beta-lactamase inhibitors against cephalosporinase-producing bacteria; Kitzis MD et al.; Combinations of different beta-lactam antibiotics, including cefotaxime, with three beta-lactamase inhibitors were tested against cephalosporinase producing bacterial strains . The most significant antagonism was obtained with a combination of clavulanic acid and cefotaxime, while almost no antagonism was observed with sulbactam and tazobactam . In strains belonging to five different species there was a correlation between the levels of cephalosporinase produced after exposure to different concentrations of inhibitors and the MICs of cefotaxime combined with the same concentrations of inhibitors . It is concluded that there is little likelihood of antagonism between beta-lactam antibiotics and sulbactam or tazobactam. J Pharmacol Exp Ther, 1989 Sep, 250(3), 979 - 84 Transport of imipenem, a novel carbapenem antibiotic, in the rat central nervous system; Suzuki H et al.; The transport of imipenem, a novel carbapenem antibiotic, in the rat central nervous system (CNS) was studied using in vivo, in situ and in vitro experimental techniques . After i.v . bolus administration, the imipenem concentration in the cerebrospinal fluid (CSF) rose to a peak within 30 min and declined with time . The CSF/serum unbound concentration ratio of imipenem was 0.22 at 2 hr after i.v . administration, substantially higher than that reported for benzylpenicillin . By using an in situ brain perfusion technique, we found that imipenem was transported through the blood-brain barrier principally via passive diffusion with a permeability-surface area product comparable to that of mannitol . In vitro, imipenem was accumulated by the isolated choroid plexus via an active organic anion transport system, although much less rapidly than benzylpenicillin . In vivo, after i.c.v . administration, imipenem was cleared from the CNS in a manner comparable to that of mannitol with only a small probenecid-sensitive process . Imipenem thus has minimal affinity for the organic anion transport system in the choroid plexus, resulting in the slow elimination of this drug from the CNS . These results suggest that the difference between imipenem and benzylpenicillin in the ratio of CSF to unbound serum drug concentration is determined principally by the efflux process in the choroid plexus rather than the influx process through the blood-brain barrier. Am J Med, 1989 Sep, 87(3), 301 - 5 Cost-effectiveness of outpatient parenteral antibiotics: a review of the literature; Balinsky W et al.; The results of studies completed on parenteral antibiotic therapy administered in an outpatient setting are reviewed . Although they varied in both size and sophistication, the studies all found that when patients and their families were carefully screened, outpatient therapy was a cost-effective, safe method of administering intravenous antibiotics . The methods used to compare the costs of inpatient and outpatient intravenous antibiotic therapy varied widely . Only direct costs were included in the early comparisons of inpatient and outpatient therapy, whereas the more recent studies included both direct and indirect costs and benefits . All studies found cost savings in the outpatient setting . Unfortunately, very few elderly patients were included because of a Medicare requirement that intravenous antibiotic therapy be administered or supervised by a physician . However, beginning in 1990, the Medicare Catastrophic Coverage Act of 1988 will cover intravenous drugs administered at home . Thus, it will be possible to study applicability of this therapy for the elderly population. J Chromatogr, 1989 Aug 30, 477(2), 259 - 70 Separation of beta-lactam antibiotics by micellar electrokinetic chromatography; Nishi H et al.; The retention behaviour of beta-lactam antibiotics in micellar electrokinetic chromatography (EKC) was investigated . Sodium dodecyl sulphate (SDS) and sodium N-lauroyl-N-methyltaurate were used an anionic surfactants at concentrations of 0.05-0.3 M . It was found that the retention of ionic substances in micellar EKC is determined by the following three factors: the electrophoretic migration of the ionic substances, the interaction between the ionic substances and ionic surfactants and solubilization of the solute by the micellar phase . A difference in the retention behaviours of cationic substances was observed between the two anionic surfactants, which have different groups neighbouring the charge-bearing groups . The effect of an ion-pairing reagent was also investigated to make the effect of the micelle clearer . All test solutes were successfully separated by micellar EKC at SDS concentrations above 0.1 M, with theoretical plate numbers ranging from 70,000 to 260,000. Anal Biochem, 1989 Aug 15, 181(1), 90 - 5 Reductive methods for isotopic labeling of antibiotics; Champney WS; Methods for the reductive methylation of the amino groups of eight different antibiotics using 3HCOH or H14COH are presented . The reductive labeling of an additional seven antibiotics by NaB3H4 is also described . The specific activity of the methyl-labeled drugs was determined by a phosphocellulose paper binding assay . Two quantitative assays for these compounds based on the reactivity of the antibiotic amino groups with fluorescamine and of the aldehyde and ketone groups with 2,4-dinitrophenylhydrazine are also presented . Data on the cellular uptake and ribosome binding of these labeled compounds are also presented. JAMA, 1989 Aug 11, 262(6), 813 - 6 Antibiotic therapy for cat-scratch disease? Bogue CW, Wise JD, Gray GF, Edwards KM. Cat-scratch disease is usually a benign, self-limited disease that causes regional lymphadenopathy . Occasionally, it may present with systemic symptoms and have a prolonged course . To date, antibiotic therapy has not been proved to be of value . We describe three patients with cat-scratch disease who were treated successfully with gentamicin sulfate . Two patients had extensive hepatic involvement, and one patient had regional lymphadenopathy . All three patients responded within 48 hours to intravenous gentamicin . Extensive follow-up has shown no recurrence of symptoms . These cases suggest that gentamicin may be efficacious in shortening the course of cat-scratch disease . Prospective, randomized trials should be performed to confirm these results. N Z Med J, 1989 Aug 9, 102(873), 409 - 11 Antibiotic therapy costs; Atkinson HC et al.; The total cost of antibiotics, rather than acquisition costs alone was estimated . Preparation and administration costs, laboratory and monitoring costs, and labour costs are considered separately for the major antibiotics used within Christchurch Hospital . The oral route of antibiotic administration is by far the cheapest . The cost of infusion therapy compared with an IV push is considerable . This added about +15-+30 in equipment costs and another +20-+30 in labour costs and often constituted over 50% of the total cost of therapy . The cost of adverse reactions and differences in efficacy should ultimately be included but it was impossible to quantitate these factors in terms of absolute costs . Acquisition costs alone are a poor guide to the true costs of therapy . The cost of administering the drug should be considered in the contexts of efficacy, toxicity and impact on the environment . We contend that these considerations should be implied to the overall impact on the hospital budget, rather than the pharmacy costs alone. Hosp Formul, 1989 Sep, 24(9), 513 - 6, 519-20, 523 A multicenter model for examining in vitro susceptibilities of bacteria to antibiotics; Day D et al.; In vitro bacterial susceptibility data are often considered in both hospital formulary and antibiotic prescribing decisions . In this multicenter study, susceptibility data from 105 United States hospitals resulted in a database containing 211,142 isolates for 31 different bacteria and 38 antibiotics . To identify susceptibility patterns of bacteria to antibiotic alternatives, this computerized database was subjected to confidence interval analysis, while controlling for potential sources of random error . This paper describes the multicenter study design and provides several examples of the type of information the analysis can provide to P & Committee members and to practitioners who ultimately must make decisions regarding antibiotic use, sometimes without the benefit of complete hospital-specific historical antibiogram data . Limitations on the interpretation of aggregate in vitro susceptibility data gained from multiple institutions are also discussed. Antimicrob Agents Chemother, 1989 Aug, 33(8), 1286 - 90 Measurement and clinical and pharmacokinetic implications of diffusion coefficients of antibiotics in tissues; Meulemans A et al.; A method for determining diffusion coefficients of four antibiotics in extracellular tissue space according to Fick's law is described . This new method was applied to rat brain tissue and to agar . After diffusion of the antibiotic in one axis, the gradient concentration was determined with microvoltammetric electrodes . These microelectrodes (1 micron at the extreme tip) measured the free diffusible form of electroactive antibiotics in the extracellular brain space . Metronidazole, chloramphenicol succinate, cefsulodin, and piperacillin gave diffusion coefficients ranging from 0.1 x 10(-6) to 0.2 x 10(-6) cm2 . s-1 in tissue; chloramphenicol base, which is positively charged, gave a coefficient of 0.04 x 10(-6) cm2 . s-1 . The coefficient ranged from 0.6 x 10(-6) to 1.2 x 10(-6) cm2 . s-1 in agar . These coefficients were used to simulate antibiotic concentrations in infectious sites and between capillaries by using a simple model of plane diffusion. J Antimicrob Chemother, 1989 Aug, 24(2), 251 - 64 Structural correlations with cross-reactivity of beta-lactam antibiotics in delayed type hypersensitivity . Cross-allergenicity in hypersensitivity to cephems with a tetrazolyl group in the C-3 side chain; Uno K et al.; Cross-reactivity associated with delayed type hypersensitivity (DTH) arising from cephem antibiotics with a tetrazolyl group in the C-3 side chain was investigated by clinical testing and animal experiments . Clinical cross-reaction testing was performed with the leucocyte migration inhibition test (LMIT) with respect to sixteen patients with hypersensitivity induced by cephems with a tetrazolyl group in the C-3 side chain . The proportion of positive LMIT cross-reactions to cephems with a tetrazolyl group in the C-3 side chain was 78% (25/32), to cephems without a tetrazolyl group, 5% (1/22), and to penams, 0% (0/12) . The proportion of positives in tests performed with methyl-tetrazolethiol (MTT) and hydroxyethyl-tetrazolethiol (HTT), which essentially represent the structures of the C-3 side-chains in the allergenic drugs, was 29% (4/14), while the corresponding proportion for 7-aminocephalosporanic acid (7ACA), which represents the skeleton structure of the cephem antibiotics, was 33% (1/3) . The animal experiments were performed with guinea pigs, with latamoxef, cefoperazone and MTT as the sensitizing agents and testing for cross-reactivity by means of delayed type intradermal reactions as well as the LMIT . The results of intradermal testing and the LMIT agreed almost completely, thus providing strong support for the clinical results . Latamoxef and cefoperazone displayed the same cross-reactivity, manifesting cross-reactions with MTT, HTT and 7ACA as well as with cephems having a tetrazolyl group in the C-3 side chain . Moreover, DTH induced by MTT displayed cross-reactivity with cephems possessing tetrazolyl groups in the C-3 side chain . The above results indicate that free MTT radicals, as well as the skeleton ring structure represented by 7ACA, are strongly involved in DTH arising from cephem antibiotics with a tetrazolyl group in the C-3 side chain. J Antimicrob Chemother, 1989 Aug, 24(2), 241 - 50 Application of leucocyte migration tests to detection of allergenic drugs in patients with hypersensitivity to beta-lactam antibiotics; Uno K et al.; In 90 suspected cases of beta-lactam hypersensitivity manifesting exanthema, pyrexia and hepatopathic symptoms, the identities of the allergenic drugs were investigated by immediate type skin reactions, sensitized erythrocyte agglutination tests and leucocyte migration inhibition tests (LMIT) . In addition 30 control patients were tested for hypersensitivity to ampicillin, cephalexin and latamoxef . The control patients manifested the same symptoms as the patients with suspected hypersensitivity to beta-lactam but had not been treated with beta-lactam antibiotics . In the immediate type skin reaction, all the control cases as well as all the suspected beta-lactam hypersensitive patients displayed negative reactions to each of the antibiotics tested . In the sensitized erythrocyte agglutination tests, no antibodies to any of the three drugs were detected in the control group, while antibodies with a titre of 1:2 or more were detected in only 7% (6/90) of the suspected beta-lactam hypersensitive patients . On the other hand, in the LMIT, only 4% (4/90) of the control patients displayed positive reactions to the three test antibiotics, whereas the suspected sensitizing drugs elicited a high rate of positive responses (68/90; 76%) in the group of suspected beta-lactam hypersensitive patients . Broken down into symptomatic categories, response to the LMIT was positive in 41 of 58 cases of suspected drug rash (71%), 26 of 26 cases of suspected drug fever (96%), and 20 of 24 cases of suspected drug-induced hepatopathy (83%) . Thus, the pyrexial group exhibited a particularly high ratio of positive reactions, and in fact exanthemic cases with concomitant symptoms (eosinophilia, pyrexia, hepatopathy, etc.) also displayed a notably high ratio of positives (19/20; 95%) . The overall results indicated that delayed type hypersensitivity (DTH) is largely involved in exanthema, pyrexia and hepatopathy induced by beta-lactam antibiotics, and that the LMIT constitutes an effective means of detecting allergenic drugs in patients with beta-lactam hypersensitivity. Crit Care Med, 1989 Aug, 17(8), 772 - 9 Oxygen consumption and central hemodynamics in septic shock treated with antibiotics, fluid infusions, and corticosteroids; Ottosson J et al.; The multidimensional pathophysiology of septic shock is poorly understood and treatment modalities are controversial . The present study evaluates the relative importance of three therapeutic measures: antibiotics (trimethoprim and sulphamethoxazole {TS}); fluid infusions (lactated Ringer's solution {RL} and 3% albumin {Alb}), and pharmacologic doses of corticosteroids (CS) (dexamethasone {DM}), using central hemodynamics (plasma volume {PV}, cardiac output, oxygen consumption {VO2}), and survival as end-points . Septic shock was induced by intraperitoneal injection of live Escherichia coli bacteria . At 5 h in untreated septic rats, PV had dropped to 76%, cardiac output to 69%, and VO2 to 71% of preshock levels . Untreated septic animals had a mean survival time of 9.7 +/- 1.7 (SD) h, with none surviving 24 h . Regardless of therapy, cardiac output and VO2 at 10 h were predictors of survival time (p less than .01) . Treatment was initiated at 5.5 h after bacterial injection, at a time when TS therapy alone had not improved the 24-h survival rate . Animals treated with DM, RL, and Alb, in this order, exhibited progressively improved central hemodynamics, and 24-h survival rate increased to 60% compared with 0 in untreated animals (p less than .001) . The combination of DM and RL produced no further improvement . However, DM combined with 3% Alb restored VO2, cardiac output, and PV to 81%, 100%, and 125%, respectively, increasing the 24-h survival rate to 97% (29/30), significantly greater than that achieved by any other treatment modality (p less than .05). J Antibiot (Tokyo), 1989 Aug, 42(8), 1294 - 8 A new macromolecular antitumor antibiotic, C-1027 . III . Antitumor activity; Zhen YS et al.; C-1027, a new macromolecular antitumor antibiotic produced by Streptomyces globisporus C-1027, showed extremely potent cytotoxicity toward cultured cancer cells . Compared in terms of IC50 values, antibiotic C-1027 showed much more potent cytotoxicity than doxorubicin, mitomycin C and neocarzinostatin . Spermatogonial assay, a prescreen for anticancer drugs, was highly sensitive for detection of C-1027 . At tolerable doses, C-1027 exhibited marked inhibition on a panel of transplantable tumors in mice, which included leukemia L1210, P388, ascites hepatoma H22, sarcoma 180 and melanoma Harding-Passey. J Med Chem, 1989 Aug, 32(8), 1782 - 8 Brain-specific chemical delivery systems for beta-lactam antibiotics . In vitro and in vivo studies of some dihydropyridine and dihydroisoquinoline derivatives of benzylpenicillin in rats; Wu WM et al.; Four chemical delivery systems (CDS's) based on a dihydropyridine----quaternary pyridinium salt redox system were used for the brain delivery of benzylpenicillin (BP) . CDS's 5 and 9 are diesters of C1 and C2 diols in which one hydroxyl group is esterified by the benzylpenicillin-3-carboxylic group and the other by dihydrotrigonelline . CDS's 13a and 17 are benzylpenicillin esters of amino alcohols in which the amine group is acylated by dihydro-trigonelline (13a) or by 1,2-dihydro-2-methyl-4-isoquinolinecarboxylic acid (17) . In vitro relative stability studies showed that both CDS's and quaternary pyridinium salts were quite unstable in rat and rabbit blood or brain but much more stable in dog or human blood . Kinetic studies performed in rat brain homogenate demonstrated the facile enzymatic oxidation of the CDS's to the corresponding quaternary salts . Hydrolysis of the CDS's and the quaternary salts resulted in the release of benzylpenicillin . In biological media CDS 13a also yielded a water addition product, the 6-hydroxy-1,4,5,6-tetrahydropyridine derivative . In vivo distribution studies were carried out in rats . After iv administration of equimolar doses of BP and CDS's, brain benzylpenicillin levels were found to be substantially higher and more prolonged in case of 5 and 9 than of BP itself . However, administration of 13a and 17 resulted in lower brain benzylpenicillin levels due to the water addition reaction and a nonspecific brain delivery, respectively . The remarkable increase of BP levels as well as the prolonged effect after the administration of 5 and 9 is a result of an improved penetration through the blood-brain barrier of the lipophilic CDS's and a "lock-in" effect of the corresponding quaternary salts generated in situ. J Med Chem, 1989 Aug, 32(8), 1774 - 81 Brain-specific chemical delivery systems for beta-lactam antibiotics . Synthesis and properties of some dihydropyridine and dihydroiosquinoline derivatives of benzylpenicillin; Pop E et al.; Six chemical delivery systems (CDS) were synthesized for benzylpenicillin in order to improve its transport across the blood-brain barrier . The CDS's were based on a dihydropyridine----quaternary pyridinium ion redox system, analogous to the naturally occurring NADH----NAD+ system . Two different types of CDS's were prepared: benzylpenicillin esters of diols in which the other hydroxyl group is esterified by dihydrotrigonelline and benzylpenicillin esters of amino alcohols in which the amine group is acylated by dihydrotrigonelline, or by 1,2-dihydro-2-methyl-4-isoquinolinecarboxylic acid . Lipophilicities of the CDS's were proved to be much higher than those of benzylpenicillin by using Rm values as lipophilicity indexes . Upon oxidation, all of the CDS's gave the quaternary ion forms . Kinetic studies in buffer (pH profiles) indicated that the quaternary salts released benzylpenicillin in pH range of 5-9 via hydrolysis . The CDS's in acidic media yielded as the major reaction product 6-hydroxy-1,4,5,6-tetrahydropyridines as a result of water addition, while in basic conditions benzylpenicillin was released . The water addition reaction was dependent on the CDS's structure, being more prevalent in the case of the "amide-esters" . The dihydroisoquinoline CDS was rather stable in the pH range 5-8. J Chemother, 1989 Aug, 1(4), 261 - 5 Controlled trial of the prophylactic administration of antibiotics in sclerotherapy of esophageal varices; Pulanic R et al.; The aim of this controlled trial was to determine the usefulness of chemoprophylaxis in sclerotherapy of ruptured esophageal varices . Sixty patients bleeding from esophageal varices, without signs of infection at admission, were included in a randomized open trial of one-year duration . Thirty patients received, along with the usual standard therapy (infusions, transfusions) 4x1 g ampicillin intravenously over 3 days, and 30 patients received the standard therapy only . Bleeding varices of the esophagus were sclerosed transendoscopically intravenously using 1% polidocanol solution . Body temperature, general condition, white blood count, differential blood count and sedimentation rate were followed-up over three days . There were no statistically significant differences between the groups in the mean values of the mentioned parameters . There was no correlation between the dose of sclerosant used and body temperature or leukocyte count . Chemoprophylaxis proved to have no effect in this indication. South Med J, 1989 Aug, 82(8), 960 - 2 Efficacy of prophylactic antibiotics for the prevention of endomyometritis after forceps delivery; Heitmann JA et al.; The purpose of this prospective randomized controlled clinical trial was to determine whether prophylactic antibiotics reduce the incidence of endomyometritis after forceps delivery . Of the 393 patients studied, 192 received 2 gm of intravenous cefotetan after forceps delivery, and 201 patients received no antibiotics . There were seven cases of endomyometritis in the group given no antibiotic and none in the cefotetan group, a statistically significant difference (P less than .01) . We conclude that prophylactic antibiotics are effective in reducing the incidence of endomyometritis after forceps delivery . We believe this is the first published study demonstrating this benefit. J In Vitro Fert Embryo Transf, 1989 Aug, 6(4), 236 - 41 Isolation of Mycoplasma bovis from intact and microinjected preimplantation bovine embryos washed or treated with trypsin or antibiotics; Bielanski A et al.; Incubation of day 7 bovine embryos with 10(4) or 10(6) CFU/ml of Mycoplasma bovis (M . bovis) or microinjection of M . bovis into the cells of day 7 embryos did not influence embryonic development . M . bovis was recovered from all embryos washed 10 times by a standard pipetting method or vortexed and pipeted 10 times . M . bovis was also recovered from zonae pellucidae removed and washed from microinjected embryos . Neither treatment with trypsin nor exposure of embryos to combinations of penicillin, streptomycin, lincomycin and spectinomycin, or gentamicin, tylosin, lincomycin, and spectinomycin, inactivated M . bovis. Antibiot Khimioter, 1989 Aug, 34(8), 614 - 20 {Pharmacokinetic monitoring of antibiotic therapy}; Firsov AA; The general strategy in optimization of antibiotic dosage regimens included development of population or common regimens for an "average" patient (the 1st approximation), subpopulation regimens for patients of certain categories on the basis of interactions between the pharmacokinetic parameters and "patient factors" (the 2nd approximation) and individual regimens on the basis of the data of the pharmacokinetic monitoring (the 3rd approximation) . Characteristics of every of the approximations in antibiotic therapy of adults and children were analyzed . Out of the peculiarities of the strategy use in pediatrics+ and micropediatrics+ the following should be indicated: (1) pharmacokinetic heterogeneity of the population requiring grouping of the patients and consequently development of subpopulation dosage regimens omitting stage I, (2) possible development of dosage regimens on the basis of the ration between the pharmacokinetic parameters or immediate drug concentration values and the "patient factors" not only in chronic but also in transitory impairment of some functions and (3) the necessity of considering systematic changes in "pharmacokinetic status" of every child during individualization of the dosage regimens by the data of the pharmacokinetic monitoring. Antibiot Khimioter, 1989 Aug, 34(8), 606 - 9 {Effect of carbohydrates on possible utilization of wastes from antibiotic-manufacturing plants in the construction industry}; Tarakanov OV et al.; Utilization of antibiotic manufacture waste containing a certain amount of carbohydrates in concrete preparation requires their control . It was shown that the content of not more than 0.5 per cent of carbohydrates in the waste had no unfavourable effect on the concrete hardening. Antibiot Khimioter, 1989 Aug, 34(8), 593 - 6 {Effect of the antineoplastic antibiotic bruneomycin on lymphocyte population ratio in mice}; Vatin OE; Data on the quantitative ratio of the populations of T- and B-cells in the lymphoid organs of mice at various periods after oral administration of bruneomycin are presented . It was shown that in contrast to the total number of T- and B-cells in the spleen and mesenteric lymph nodes amounting to the minimal values at the early periods (days 1-3) after the antibiotic injection, their relative content remained rather high . Complete recovery of the number of T- and B-lymphocytes in the above organs was observed only by the end of a month period . Study on the kinetics of the immune response to sheep red blood cells showed that reactivity of the antibody producers in the experiments with bruneomycin increased 1.5-2 fold as compared to the control. J Bacteriol, 1989 Aug, 171(8), 4518 - 20 Induction of ermC methylase in the absence of macrolide antibiotics and by pseudomonic acid A; Kadam SK; The methylase encoded by erm genes and induced by erythromycin modifies the 23S rRNA and confers resistance to macrolide-lincosamide-streptogramin B antibiotics . Induction is due to a posttranscriptional mechanism in which the inducer activates translation of methylase mRNA by binding to unmethylated (erythromycin-sensitive) ribosomes and stalling them in the leader region . It is shown in this study that pseudomonic acid A, an inhibitor of isoleucyl-tRNA synthetase, can also induce methylase synthesis . Isoleucine starvation has a similar effect on ribosomes translating the ermC leader region to cause induction of methylase synthesis . These observations support the requirements for ribosome stalling and destabilization of a stem-loop structure and demonstrate that stalling can occur without macrolide-bound ribosomes. Enferm Infecc Microbiol Clin, 1989 Aug-Sep, 7(7), 349 - 53 {Use of aminoglycoside antibiotics in a general hospital: kinetics consequences in those patients whose blood levels are not monitored}; Saucedo R et al.; A surprise monitoring of plasma aminoglycoside level was carried out in our Hospital in 55 patients . Basal samples and samples one hour after i.m . or i.v . administration were obtained . A protocol sheet with personal, clinical and therapeutic data was filled for each patient . The FPIA analysis technique (CV less than 5%) was used . Only the data related to gentamicin were evaluated, because the number of patients receiving other aminoglycosides was very low (5 cases) . The most usual dose and interval were 80 mg (91%) and 12 hours (69%), respectively . The administration routes were i.v . (52%) and i.m . (48%) . Blood urea and/or creatinine levels were not measured in 22% of patients . The baseline gentamicin levels were subtherapeutic in 30%, therapeutical in 57%, and toxic in 13%, and 50%, 46% and 4%, respectively, for the levels after one hour . In patients with abnormal renal function a good correlation could be demonstrated (r = 0.96; p less than 0.001) between creatinine level and gentamicin 1/2 time . This correlation was absent in patients with normal renal function . When the dose of the antibiotic was adjusted to the weight of the patient, the frequency of therapeutic levels was higher (47%; p less than 0.03); in these cases, the most common administration interval was 8 hours (p less than 0.01) . We emphasize the lack of control of the renal function in 22% of patients, stressing that the lack of monitoring systematically results in potentially subtherapeutic levels in more than one half of the investigated patients (57%). Hindustan Antibiot Bull, 1989 Aug-Nov, 31(3-4), 83 - 9 Effect of antibiotics in controlling the production of cell wall degrading enzymes in vitro and disease development in vivo; Chopra S et al.; Production of cellulolytic, proteolytic and pectolytic enzymes by all the three isolates of A . niger was inhibited by all the tested antibiotics . Nystatin (500 ppm) could cause complete inhibition of PG enzyme production, whereas PMG production was checked by amoxicillin, nystatin, chloramphenicol and raficillin at 100 ppm concentration . All the antibiotics at 500 ppm concentration checked the cellulase production in all the three isolates of A . niger . Nystatin and raficillin (100 ppm) completely controlled the protease production in all the three isolates of A . niger . A positive correlation was observed with enzyme production and mycelial biomass in three isolates of A . niger, All the antibiotics at both the concentrations (100 and 500 ppm) could also check the rottening in all the three fruits in vivo conditions. Nucleic Acids Res, 1989 Jul 25, 17(14), 5447 - 59 High resolution hydroxyl radical footprinting of the binding of mithramycin and related antibiotics to DNA; Cons BM et al.; The preferred binding sites for mithramycin on three different DNA fragments have been determined by hydroxyl radical footprinting . Sequences which appear as one long protected region using DNAase I as a footprinting probe are resolved into several discrete binding domains . Each drug molecule protects three bases from radical attack, though adjacent regions show attenuated cleavage . Mithramycin and the other related compounds induce similar footprinting patterns and appear to recognise GC rich regions with a preference for those containing the dinucleotide step GpG . The ability of each such site to bind the drug depends on the sequence environment in which it is located . The data are consistent with mithramycin binding to the DNA minor groove. J Chromatogr, 1989 Jul 14, 474(1), 317 - 27 Liquid chromatographic-mass spectrometric studies on rifamycin antibiotics; Vekey K et al.; The use of a direct liquid introduction type liquid chromatographic-mass spectrometric interface to study highly thermally labile rifamycin antibiotics is described . Using negative ionization, abundant molecular ions were observed, and the spectra, also contained structurally significant fragments . Variation of the high-performance liquid chromatographic parameters did not change the spectra, thus making it easy to change chromatographic conditions . In quantitative studies, a surprising correlation was found, indicating that the mass spectrometric signal was proportional to the square of the sample concentration. Biochim Biophys Acta, 1989 Jul 10, 982(2), 303 - 6 The polyene antibiotic amphotericin B acts as a Ca2+ ionophore in sterol-containing liposomes; Ramos H et al.; Amphotericin B (AmB) was shown to induce a Ca2+ influx across ergosterol- and cholesterol-containing large unilamellar liposomes, by following spectrophotometrically the formation of the Arsenazo III-Ca2+ complex . At equivalent antibiotic concentrations the Ca2+ influx was much more extensive through ergosterol-containing membranes (almost 100% with 1 microM AmB, 160 microM lipid) than through cholesterol-containing membranes (below 0.5 microM the influx of Ca2+ was negligible) . In the presence of ergosterol-containing membranes the initial rate of Ca2+ influx had the same linear dependence on the ratio antibiotic/lipid whatever the lipid concentration, which was not the case in cholesterol-containing membranes . These results suggest that the channels responsible for the AmB-induced Ca2+ permeability across cholesterol- and ergosterol-containing liposomes have different structures. Can J Hosp Pharm, 1989 Aug, 42(4), 137 - 41 A review of the Manitoba home i.v . antibiotic program; Cote D et al.; The Manitoba Home IV Antibiotic Program was reviewed after 12 years of operation . Patient selection and the steps involved in sending a patient home on the program are outlined . The types of infections treated and the incidence of complications and therapeutic failures are presented . The drugs and supplies used are described and total costs are discussed . The data presented is based on 748 patient admissions to the program and 15,366 patient days of experience . The review concludes that the program is safe and effective and provides a viable alternative to hospitalization for patients with chronic infections. Antibiot Khimioter, 1989 Jul, 34(7), 504 - 10 {Effect of beta-lactam antibiotics on lipid bilayer membranes . II . Cephalosporin antibiotics}; Taisova AS et al.; Interaction of cephalosporin antibiotics with flat bilayer lipid membranes (BLM) composed of vegetative or bacterial phospholipids was studied with respect to their effect on electroconductivity, capacity for binding to the bilayers and capacity for transmembrane transfer through the bilayers . By their effect on conductivity, the investigated cephalosporins could be divided into three groups: those having no effect on conductivity at the maximum concentrations (up to 1 mg/ml) i.e . cefoperazone, cefotaxime and ceftizoxime, those having an effect on conductivity at concentrations of 0.2 to 0.5 mg/ml i.e . cephalexin and cephalothin and those having a significant effect on conductivity at concentrations of 10 to 60 micrograms/ml i.e . N-acyl derivative of 7-ACA (substance 64) and 7-ACA derivative (substance 71) . The cephalosporins had a capacity for binding to the bilayers and for incorporation into the bilayers . They penetrated to some extent through the bilayers composed of either vegetable or bacterial phospholipids . The lower rate of penetration through the BLM as compared to that of penicillins must be due to lower hydrophobicity of the cephalosporin molecules as compared to that of penicillins. Antibiot Khimioter, 1989 Jul, 34(7), 496 - 504 {Effect of beta-lactam antibiotics on lipid bilayer membranes . I . Penicillin antibiotics}; Taisova AS et al.; Interaction between penicillins and model membrane systems, flat black bilayer lipid membranes (BLM) composed of vegetable or bacterial phospholipids was studied with an account of the complicated structure of bacterial cell membranes and possible presence in them of "pure" bilayer lipid areas . By their effect on electroconductivity of the BLM the antibiotics could be divided into three groups: those having no effect on the BLM electroconductivity at the maximum concentrations i.e . benzylpenicillin, carbenicillin, piperacillin (at pH 6.0 and 7.0) and ampicillin (at pH 6.0), those insignificantly changing electroconductivity of the BLM i.e . carfecillin and azlocillin and those having a significant effect on the BLM electroconductivity i.e . ampicillin N-acyl derivatives and 6-APA . The effect of ampicillin on the BLM conductivity markedly depended on the electrolite pH . The penicillins bound to the bilayer and induced changes in the transmembrane potential (evident from the changes in the second harmonic of the capacitive current) and the BLM elasticity-capacitance parameters (evident from the changes in the ratio of the amplitudes of the first and third harmonics) . It was shown that all the penicillins penetrated through the BLM composed of either vegetable or bacterial phospholipids . The capacity for the transmembrane transfer without changing of the bilayer conductivity must be connected with the fact that the penetrating antibiotics did not induce any changes in the BLM structure . The effect on the conductivity probably depended in its turn on the form of the molecule and the ratio of the hydrophilic and hydrophobic parts in it. Kidney Int, 1989 Jul, 36(1), 78 - 88 Contraluminal organic anion and cation transport in the proximal renal tubule: V . Interaction with sulfamoyl- and phenoxy diuretics, and with beta-lactam antibiotics; Ullrich KJ et al.; In order to study the interaction of sulfamoyl- and phenoxy diuretics as well as of beta-lactam antibiotics with the contraluminal anion and cation transport systems the inhibitory potency of these substances against the influx of 3H-para-aminohippurate, 14C-succinate, 35S-sulfate and 3H-N1-methylnicotinamide into cortical tubular cells have been determined . 1.) 2-, 3- and 4-sulfamoylbenzoate inhibit contraluminal PAH influx . N-dipropyl substitution to yield probenecid or ring-substitution to yield furosemide and piretanide augment the inhibitory potency . However, hydrochlorothiazide and acetazolamide exert only a moderate inhibitory potency . Succinate transport was inhibited by furosemide only . Sulfate transport was inhibited by furosemide and 3-sulfamoyl-4-phenoxybenzoate as well as by probenecid, piretanide, hydrochlorothiazide and acetazolamide . 2.) Phenoxyacetate, -propionate, and -butyrate exert increasing inhibition against PAH transport . The weed-killers 2,4-dichloro-, and 2,4,5-trichlorophenoxyacetate (2,4 D and 2,4,5 T) had a similar inhibitory potency, while ethacrynic acid showed a lower and the uricosuric tienilic acid a higher inhibitory potency . None of the compounds of this group interact with contraluminal succinate transport, and only the multiring-substituted compounds 2,4 D, 2,4,5 T, ethacrynic and tienilic acid interact slightly with the sulfate transporter . 3.) The monocarboxylic penicillins benzylpenicillin and phenoxymethylpenicillin as well as the dicarboxylic ticarcillin interact with the contraluminal PAH transport . The aminopenicillin ampicillin had a lower, and apalcillin a higher inhibitory potency than monocarboxylic penicillin . Benzylpenicillin showed small inhibition against succinate transport and ticarcillin against sulfate transport . 4.) The monocarboxylic cephalosporine, 6315 S Shionogi, and the aminocephalosporines, cephalexin and cefadroxil, showed an app . Ki.PAH as the comparable penicillins . The zwitterions cephaloridine and cefpirome did not interact with the PAH transporter, but with the organic cation (NMN) transporter . Amongst the amino-thiazol-containing compounds cefotaxime, ceftriaxone, and cefodizime, increasing interaction with the PAH transporter was seen dependent of a second ionizable anionic group . Compounds with two ionizable anionic groups (cefsulodin, ceftriaxone, cefodizime) exert also a small inhibitory potency against sulfate transport . None of the cephalosporins interacted with the dicarboxylate transporter . The interaction pattern of the tested compounds is in accordance with the specificity requirements for the contraluminal transporters depending on electrical charge and hydrophobicity. Zhong Xi Yi Jie He Za Zhi, 1989 Jul, 9(7), 402 - 4, 388 {Clinical and experimental research on a kidney-tonifying prescription in preventing and treating children's hearing-loss induced by aminoglycoside antibiotic ototoxicity}; Lin WS et al.; This paper reports 30 cases of hearing-loss induced by aminoglycoside antibiotic ototoxicity treated mainly with Kidney-tonifying herbs such as Herba Epimedii, Rhizoma Drynariae, Rhizoma Polygonati, Radix Polygoni Multiflori, Magnetitum and Rhizoma Acori Graminei, etc . After three month's treatment, the authors found that 19 cases had improved their hearing more than 15 db, among which there are 8 cases who had improved 15 db and 11 cases 30 db . The patients' hearing of pre-treatment and post-treatment were determined by BAR V-wave hearing threshold . In order to further prove that Kidney-tonifying prescription can antagonize the aminoglycoside antibiotic ototoxicity, animal experiments had been made . The authors chose guinea pigs for experimental animals, which were randomly divided into three groups: Kanamycin group, kanamycin with Kidney-tonifying herbs group, and control group . The indexes of the experiments were the animals' helix reflection index, BAR and observation of animals' cochlear under electron microscope . As a result, the damage to hair cell of Cortis organ has marked for the animals of kanamycin group, while for kanamycin with herbs group, it was obviously slighter (P less than 0.01) . There was significant difference between the groups . The result indicates that Kidney-tonifying herbs had the effect of protecting the animals' hair cells of cortis organ against aminoglycoside antibiotic ototoxicity and thus protected the animals' hearing. Mod Pathol, 1989 Jul, 2(4), 390 - 6 Interstitial nephritis related to nonsteroidal anti-inflammatory agents and beta-lactam antibiotics: a comparative study of the interstitial infiltrates using monoclonal antibodies; D'Agati VD et al.; Acute interstitial nephritis (AIN) is a common pattern of renal injury induced by therapeutic agents . In order to characterize the types of mononuclear leukocytes infiltrating the kidney in drug-induced interstitial nephritis, a panel of monoclonal antibodies (Leu1, Leu3a, OKT8, OKM1, Leu14, OKT17, IL-2) was applied to cryostat sections of 13 renal biopsies (five non-steroidal anti-inflammatory agents (NSAID) (Group I); five beta-lactam antibiotics (Group II), 3 miscellaneous (Group III} . The majority of infiltrating mononuclear leukocytes were Leu1-positive T cells (71.7 +/- 18.7%), followed by monocytes (15.2 +/- 7.7%) and B cells (7.4 +/- 9.1%) . Leu3a/OKT8 ratio was 0.954 +/- 0.341 . Rare cells reacted with antibody to the interleukin-2 receptor (1.4 +/- 1.2%) . No statistically significant differences could be found in the percentages of T lymphocytes, B lymphocytes, monocytes, activated (IL-2+) T cells or Leu3a/OKT8 (helper/suppressor) ratios in the three groups . In Group II, the following pathologic correlations were seen: Leu3a/OKT8 versus interstitial inflammation (R = -0.848), percent Leu3a versus interstitial inflammation (R = -0.818), percent OKT17 versus tubulitis (R = 0.785), percent Leu14 versus tubular atrophy (R = -0.891), and interstitial edema (R = 0.965) . Our findings support a role for cellular immune mechanisms in the pathogenesis of AIN related to both NSAIDs and beta-lactam antibiotics. Antimicrob Agents Chemother, 1989 Jul, 33(7), 1052 - 7 Antibiotic susceptibilities of two Coxiella burnetii isolates implicated in distinct clinical syndromes; Yeaman MR et al.; Antibiotic susceptibility testing of two isolates of the Q-fever agent, Coxiella burnetii, was performed with recently and persistently infected L929 fibroblast cells . The two genetically distinct isolates, Nine Mile and Priscilla, are implicated in two different clinical disease syndromes, acute and chronic Q fever, respectively . We compared the efficacies of rifampin, doxycycline, and five 4-quinolone compounds (ciprofloxacin, difloxacin, ofloxacin, norfloxacin, and pefloxacin) in reducing persistent C . burnetii infection of L929 fibroblasts . In persistently infected cells, the Priscilla isolate was less susceptible to all antibiotics tested when compared with the Nine Mile isolate . The most effective antibiotics against the Priscilla isolate were ofloxacin, pefloxacin, and ciprofloxacin (50% inhibitory concentrations of 0.5, 2.2, and 2.5 micrograms/ml, respectively) . In persistently infected cells, the Nine Mile isolate was highly susceptible to all antibiotics tested except doxycycline . In contrast, the Priscilla and Nine Mile isolates in recently infected cells were somewhat susceptible to doxycycline; the Priscilla isolate was significantly more susceptible to ofloxacin and rifampin in recently infected host cells than in persistently infected cells . Persistently infected L929 cells were also treated with antibiotic combinations . Although ciprofloxacin and doxycycline had no synergistic effect on the Priscilla isolate, ciprofloxacin and rifampin acted synergistically . Collectively, these in vitro results are in accord with the fact that chronic Q fever in humans is generally not successfully managed with antibiotics . They also indicate that early diagnosis may be essential and that combination antibiotic therapy that includes quinolones may be effective in treating chronic Q fever. Pharmacol Res, 1989 Jul-Aug, 21(4), 405 - 14 Effect of various aminoglycoside antibiotics on glucose formation in isolated rabbit kidney-cortex tubules; Michalik M et al.; The effect of six aminoglycoside antibiotics on the rate of gluconeogenesis was studied in isolated rabbit kidney-cortex tubules incubated with various substrates . All antibiotics studied did not affect glucose formation from both malate and 2-oxoglutarate . The rank order of the drug-induced inhibition of glucose formation from lactate, pyruvate and propionate was the following: neomycin = gentamicin greater than tobramycin greater than kanamycin = amikacin greater than streptomycin . This in principle corresponds to their ability to diminish pyruvate carboxylation in isolated kidney-cortex mitochondria, as well as to their known nephrotoxic potential observed in vivo . Aminoglycoside antibiotics decreased the respiration of tubule suspension incubated with various substrates . However, the rank order of the inhibition by antibiotics of oxygen uptake was different from that observed for gluconeogenesis, suggesting that the rate of energy generation does not limit glucose formation under conditions studied. Ann Clin Lab Sci, 1989 Jul-Aug, 19(4), 266 - 79 Growth characteristics of cultured human proximal tubule cells exposed to aminoglycoside antibiotics; Sens MA et al.; It is well known that the nephrotoxic lesions that occur during aminoglycoside-induced nephrotoxicity are both dose- and time-dependent . It was the purpose of this study to determine if a cell culture model based on the human proximal tubule would exhibit similar dose- and time-dependent relationships when exposed to aminoglycosides of various nephrotoxic potential . For this determination, the human proximal tubule (HPT) cells were exposed to increasing concentrations of streptomycin, kanamycin, gentamicin, and neomycin and monitored for cell growth and toxicity over an 18-day period of exposure . Both actively-dividing and resting cells were assessed with regard to aminoglycoside exposure . At high levels of aminoglycoside exposure, linear regression analysis disclosed that the rank order of toxicity of the aminoglycosides to be: neomycin greater than kanamycin greater than gentamicin greater than streptomycin . Both actively-dividing and resting cultures of HPT cells displayed both dose- and time-dependency with regard to toxicity and the ability of the cells to regenerate in the continued presence of aminoglycoside exposure . This pattern of dose- and time-dependency was unique for each aminoglycoside and varied depending on the replicative state of the cells . With the exception of neomycin, clear evidence was obtained that toxicity and cell regeneration were occurring simultaneously throughout the time course of aminoglycoside exposure; the equilibrium between the two processes determining overall cell toxicity or regeneration . In addition, the HPT cells exposed to gentamicin displayed a unique pattern of toxicity and cell regeneration when compared to the other aminoglycosides tested, with gentamicin having an increased ability to stimulate cell proliferation . While the results obtained are in excellent agreement with that known from the clinical experience with the aminoglycosides, the dose- and time-dependency of the responses will require careful attention to growth state during employment in experimental protocols. J Antibiot (Tokyo), 1989 Jul, 42(7), 1151 - 7 Urdamycins, new angucycline antibiotics from Streptomyces fradiae . IV . Biosynthetic studies of urdamycins A-D; Rohr J et al.; The biogenetic origin of the angucycline antibiotics urdamycins A-D was studied by feeding experiments with isotope labeled precursors and by NMR analysis . Feeding experiments with {1-13C}acetate and {1,2-13C2}acetate show that the chromophores of urdamycins A and B and the angucycline 4-ring skeleton of the urdamycins C and D chromophores are formed from a single decapolyketide chain . The chromophores of the urdamycins C and D contain additional structural elements which derived from the amino acids tyrosine and tryptophan, respectively . The latter was shown by feeding deuterium-labeled tyrosine and 13C-labeled tryptophan derivatives . Feeding of {1-13C}glucose and of {U-13C3}glycerol proved that the C-glycosidic moiety and the three sugars (2 x L-rhodinose, 1 x D-olivose each) of the urdamycins arise from glucose . Experiments with 14C-labeled urdamycin A, obtained by biosynthesis from {14C}acetate, showed this compound to be a late precursor of the urdamycins C and D. J Antibiot (Tokyo), 1989 Jul, 42(7), 1026 - 36 Studies on new phosphate ester antifungal antibiotics phoslactomycins . II . Structure elucidation of phoslactomycins A to F; Fushimi S et al.; Phoslactomycins A to F are new antifungal antibiotics produced by Streptomyces nigrescens SC-273 . On the basis of physico-chemical properties and NMR studies, their structures have been determined as shown in Fig . 6 . They are characterized by possessing alpha, beta-unsaturated delta-lactone, phosphate ester, conjugated diene and cyclohexane ring moieties . The structural difference between them is ascribed to a substituent bound to the cyclohexane ring. Arch Ophthalmol, 1989 Jul, 107(7), 1055 - 60 Intravitreal antibiotic therapy with vancomycin and aminoglycoside . An experimental study of combination and repetitive injections; Oum BS et al.; We evaluated the retinal toxic reaction of combined intravitreal therapy with regimens of 1.0 mg of vancomycin hydrochloride and 400 micrograms of amikacin sulfate or 1.0 mg of vancomycin hydrochloride and 100 micrograms of gentamicin sulfate in the rabbit eye . The effects of reinjecting each combination a second or third time, separated by 48-hour intervals, were also examined by ophthalmoscopy and light and transmission electron microscopy . The initial administration of either regimen did not produce toxic reaction . After two injections, five of six eyes with vancomycin-gentamicin therapy and three of six eyes with vancomycin-amikacin therapy displayed focal areas of retinal toxic reaction on histologic study . After three injections, all eyes treated with either regimen showed histologic evidence of more advanced retinal toxic reaction primarily involving the outer retina and retinal pigment epithelium . The present study demonstrates the safety of an initial intravitreal injection of vancomycin and aminoglycoside but shows increasing retinal toxic reaction with repetitive combination therapy. J Pharmacol Exp Ther, 1989 Jul, 250(1), 324 - 8 Transport of cefodizime, a novel third generation cephalosporin antibiotic, in isolated rat choroid plexus; Nohjoh T et al.; To characterize the transport system by which cephalosporin antibiotics are accumulated by the choroid plexus, kinetic analysis of cefodizime transport was performed . Accumulation of cefodizime was against an electrochemical potential gradient via a saturable process (Km = 470 microM, Vmax = 174 nmol/ml of tissue per min) that was inhibited by metabolic inhibitors (KCN and 2,4-dinitrophenol), hypothermia, a sulfhydryl reagent (p-hydroxymer-curibenzoic acid) and anion transport inhibitors (probenecid and 4,4'-diisothiocyanostilbene -2,2'-disulfonic acid) . Accumulation of cefodizime was inhibited competitively by benzylpenicillin with an inhibition constant of aproximately 100 microM . Cefodizime inhibited competitively the accumulation of benzylpenicillin with an inhibition constant of approximately 500 microM . Kinetic analysis using 16 kinds of beta-lactam antibiotics also supported the view 1) that the transport system of cefodizime is shared by benzylpenicillin and 2) that these beta-lactam antibiotics are transported via a common transport system . These findings indicate that the major transport system of cephalosporin antibiotics in the rat choroid plexus is via a carrier-mediated active anion transport process . The affinity of beta-lactam antibiotics for this transport system in the choroid plexus may be a major factor in determining their pharmacokinetics in the cerebrospinal fluid. Infect Control Hosp Epidemiol, 1989 Jul, 10(7), 316 - 20 Improved perioperative antibiotic use and reduced surgical wound infections through use of computer decision analysis; Larsen RA et al.; A prospective study was performed over a two-year period to determine whether computer-generated reminders of perioperative antibiotic use could improve prescribing habits and reduce postoperative wound infections . During the first year, baseline patterns of antibiotic use and postoperative infection rates were established . During the second year, computer-generated reminders regarding perioperative antibiotic use were placed in the patient's medical record prior to surgery and patterns of antibiotic use and postoperative wound infections monitored . Hospitalized patients undergoing non-emergency surgery from June to November 1985 (3,263 patients), and from June to November 1986 (3,568) were monitored with respect to indications for perioperative antibiotic use, timing of antibiotic use and postoperative infectious complications . Perioperative antibiotic use was considered advisable for 1,621 (50%) patients in the 1985 sample and for 1,830 (51%) patients in the 1986 sample . Among these patients, antibiotics were given within two hours before the surgical incision in 638 (40%) of the 1985 sample and 1,070 (58%) of the 1986 sample (p less than 0.001) . Overall, postoperative wound infections were detected in 28 (1.8%) of 1,621 patients in 1985 compared with 16 (0.9%) of 1,830 such patients in 1986 (p less than 0.03) . We conclude that computer-generated reminders of perioperative antibiotic use improved prescribing habits with a concurrent decline in postoperative wound infections. Arch Intern Med, 1989 Jul, 149(7), 1603 - 4 An unforeseen complication of home parenteral antibiotic therapy; Burks JH et al.; Increasing pressure to cut the length of hospital stay has resulted in a large number of patients receiving home parenteral antibiotic therapy . We present a case of an immediate allergic reaction in a penicillin-sensitive spouse of a patient receiving parenteral mezlocillin sodium therapy . A seminal level of 42 micrograms/mL of mezlocillin was documented by bioassay. DICP, 1989 Jul-Aug, 23(7-8), 556 - 61 Bacterial resistance to antibiotics: mechanisms and prevalence in hospitals and nursing homes; Bosso JA; Bacterial resistance to antibiotics has become an increasingly distressing problem over the last few decades . In this article, known resistance mechanisms are reviewed and the extent of the problem in both hospitals and nursing homes is addressed . Suggestions for preventing the further spread of this problem are presented. Minerva Anestesiol, 1989 Jul-Aug, 55(7-8), 307 - 11 {Antibioticotherapy based on statistics in intensive therapy}; Nardi G et al.; The authors present the epidemiological data concerning nosocomial infections in their Intensive Care Unit, and discuss an antibiotic strategy statistically oriented by these data . In their experience, treatment based on statistical criteria, brought to a reduction in antibiotic consumption with particular regard to broad-spectrum antibiotics, and to a decrease in individual budget. Mikrobiologiia, 1989 Jul-Aug, 58(4), 635 - 41 {Grouping of Micromonospora based on their cultural-morphologic features, antibiotic-sensitivity and formation of antibiotics}; Bibikova MV et al.; 500 Micromonospora cultures were subdivided into nine groups on the basis of their cultural-morphological properties, the ability to produce antibiotics of certain chemical classes, and the sensitivity to 18 different antibiotics: aurantiaca (I), cinnamomea (II), cinnamomea-vinacea (III), cinnamomea-olivacea (IV), nigra (V), nigra-violacea (VI), lilacinescens (VII), coerulea (VIII) and brunnea (IX) . Cultures belonging to groups I, II, III, V and VI are moderately sensitive to most of the antibiotics and often occur in natural substrates . Black Micromonospora cultures (groups V and VI) mostly produce aminoglycoside antibiotics while brown cultures (groups II and III) form macrolide antibiotics . Cultures belonging to groups IV, VII, VIII and IX have a higher sensitivity to most of the antibiotics and are rarely isolated from natural substrates . These cultures have a weak ability to produce antibiotics. Int Surg, 1989 Jul-Sep, 74(3), 171 - 4 Hepatic intraarterial antibiotic therapy for resistant hepatic abscesses; Peretz TY et al.; Liver abscesses present a severe problematic medical entity . The traditional treatment modality consists of surgical drainage, which cannot be accomplished in all circumstances . Other modes of therapy include systemic antibiotics or percutaneous catheter drainage under ultrasonography or computerized tomography . Despite new treatment regimes liver abscesses, to date, are a potentially lethal disease, with a mortality rate of about 50% . We report an innovative approach of high dosage intrahepatic arterial antibiotic infusion for the therapy of hepatic abscesses, which are resistant to conventional treatments . A patient who underwent mastectomy for breast carcinoma, developed liver metastases one year later . She was prescribed systemic chemotherapy for one year, but no antitumor response was evident . Since ther was no evidence for extra-hepatic metastases, intraarterial hepatic chemotherapy was instituted, using an Infusaid (Mi-400) implantable pump . Marked regression of liver metastases was observed . Therapy was withheld after 19 months because of biliary sclerosis development . At this stage, the patient developed liver abscesses, which were resistant to systemic antibiotic therapy . Intraarterial antibiotic therapy, using the implantable pump, was initiated . Following the treatment, a marked improvement in the patients' clinical condition was recorded and shrinkage of the abscesses was evident by ultrasonography . The patient was free of symptoms for three months, when she was readmitted with evidence of terminal metastatic disease and sepsis . It is suggested that intrahepatic arterial antibiotic therapy is an additional mode of treatment for patients with persistent liver abscesses which fail to respond to conventional treatment. J Antibiot (Tokyo), 1989 Jul, 42(7), 1178 - 83 Inhibitory effect of antibiotic cerulenin on the respiratory burst in phagocytes . II . Inhibition by cerulenin of intracellular calcium mobilization in human neutrophils; Nakata M et al.; Generation of superoxide anion (O2-) and mobilization of intracellular Ca2+ in human neutrophils upon exposure to stimuli such as N-formylmethionylleucylphenylalanine (fMLP) were inhibited by the antibiotic cerulenin, which inhibits fatty acid and cholesterol biosynthesis . The inhibition of O2- generation and Ca2+-mobilization required certain periods of incubation with cerulenin and both abilities of the cells were gradually lost following a similar time-course . In contrast, significant Ca2+-influx from the medium was observed in cerulenin-treated cells as well as untreated cells . The results suggest that an event which coincides with the Ca2+-mobilization and not Ca2+ per se is important for the induction of O2- generation in the fMLP-stimulated cells and that this step is blocked in cerulenin-treated cells . Phorbol myristate acetate or synthetic 1-oleoyl-2-acetylglycerol were able to bypass the block and induced O2- generation in cerulenin-treated cells. Anticancer Res, 1989 Jul-Aug, 9(4), 923 - 7 Studies on retinotoxic potential of a novel antitumor antibiotic--sparsomycin--in rats; Zylicz Z et al.; Sparsomycin (Sm) is a potent inhibitor of protein synthesis with an anticancer potential . Two years after its discovery in 1962 a phase I clinical trial revealed serious drug-induced retinotoxicity . The mechanism of this toxicity still remains unresolved; however, its understanding is important for the reintroduction of Sm or one of its analogues in clinical practice . If Sm penetrates the retina, its toxic effect should be seen as inhibition of a protein(s) vital for the visual function . Treatment of healthy albino rats and Royal College of Surgeon (RCS) rats with subtoxic doses of Sm was unable to produce ocular toxic effects . Disruption of the blood-retina barrier with sodium iodate allowed Sm to decrease opsin content by only 27% . These results strongly indicate that Sm might become retinotoxic solely upon extreme conditions such as permeabilization of the blood-retina barrier which may happen only in some rare pathological situations. J Trauma, 1989 Jul, 29(7), 967 - 70; discussion 970-1 Immune enhancement by tumor necrosis factor-alpha improves antibiotic efficacy after hemorrhagic shock; Livingston DH et al.; Immunomodulation with cytokines produced by recombinant DNA technology may be useful in combatting the increased susceptibility to infection seen after shock and trauma . We investigated the effect of tumor necrosis factor (TNF) alone and in combination with an antibiotic in a model of infection after shock . Interactions of TNF with another cytokine, interferon-gamma (IFN-gamma), were also examined . Sprague-Dawley rats were bled to maintain blood pressure at 45 mm Hg for 45 minutes and then resuscitated with shed blood and saline . Animals were inoculated with 10(8) S . aureus subcutaneously and placed into one of seven treatment groups: 1) control; 2) CEF-cefazolin, 30 mg/kg IP, 30 minutes before and 4 hours after inoculation; 3) IFN-recombinant rat IFN-gamma, 7,500 U SQ, 30 minutes after inoculation and daily for 3 days; 4) TNF-recombinant human TNF, 7,500 U SQ, 30 minutes after inoculation and daily for 3 days; 5) CEF + IFN as in 2 and 3; 6) CEF + TNF as in 2 and 4; 7) CEF + IFN + TNF as in 2, 3, and 4 . Animals were sacrificed on day 7 and abscess number, diameter, and weight were measured . CEF reduced abscess diameter and weight following hemorrhagic shock, but did not affect abscess number . IFN-gamma and TNF alone did not reduce infection . The combination of either IFN-gamma or TNF with CEF significantly decreased infection following shock compared to control or CEF alone . CEF + TNF decreased abscess number compared to CEF + IFN (14/20 vs . 7/20;p less than 0.05) but did not alter abscess diameter.(ABSTRACT TRUNCATED AT 250 WORDS) Chem Pharm Bull (Tokyo), 1989 Jul, 37(7), 1827 - 30 Determination of beta-lactam antibiotics in water by fluorescence quenching of mercurochrome, and application for simple investigation of potency; Mori I et al.; The fluorescence quenching reaction between fluorescein mercury or halogeno-fluorescein mercury compounds (fl . Hg, 2,7- or 2,4-dichloro-fl.Hg, 3',4',5',6'-tetrachloro-fl.Hg, mercurochrome) and beta-lactam antibiotics (ampicillin (AB-PC) and cephalexin (CEX} was investigated, and mercurochrome was selected for the detection of beta-lactam antibiotics; the detection limit was about 0.8 micrograms/ml . A fluorimetric assay of beta-lactam antibiotics was established by measuring the fluorescence of mercurochrome and mercurochrome-beta-lactam antibiotics solutions in weakly basic media to determine the degree of fluorescence quenching . The maximum emission wavelength of mercurochrome solution was at 544 nm with excitation at 470 nm . The calibration graphs were linear over the ranges of about 0-6 micrograms/ml beta-lactam antibiotics penicillins (AB-PC, penicillin G, sulbenicillin, amoxicillin, cyclacillin, oxacillin, hetacillin and piperacillin) and cepham antibiotics (CEX, cefazolin, cephaloglycin, cephaloridine and cefpyramide), and the relative standard deviation was 2.7% for 1.4 micrograms/ml of AB-PC (n = 5) . This fluorescence quenching reaction between mercurochrome and beta-lactam antibiotics was applied in a survey of decomposition and remaining potency of beta-lactam antibiotics. Biochim Biophys Acta, 1989 Jun 6, 981(2), 207 - 12 Polydispersity of aggregates formed by the polyene antibiotic amphotericin B and deoxycholate . A spin label study; Lamy-Freund MT et al.; The amphotericin B-deoxycholate (AB-DOC) system (1:2, mole basis) was studied with regard to its organizational properties making use of spin label ESR spectra . The spectra of a fatty acid spin label intercalated in AB-DOC preparations revealed two components, one strongly (S) and one weakly (W) immobilized . Spectral subtractions indicated that S corresponds to label in mixed AB-DOC aggregates while W is due to label in deoxycholate micelles . This situation, coexistence of different aggregates, is similar to that found in systems consisting of bile salts and phospholipids . The DOC/AB mole ratio in the mixed aggregate is highest when pure DOC micelles are present . Dilution leads to disappearance of the latter and to continuous loss of DOC from AB-DOC accompanied by an increase in size and decrease in solubility of the aggregates, as verified by filtration and centrifugation experiments . The results indicate that AB-DOC systems are polydisperse . Since amphotericin B preparations having different organizational properties display different toxic and therapeutic effect, the study of amphotericin B aggregates should help in understanding these phenomena at a molecular level. Med J Aust, 1989 Jun 5, 150(11), 619 - 23, 626 A decade of antibiotic use in a teaching hospital; Raymond PM et al.; A survey of the antibiotic agents that are being prescribed for inpatients in St Vincent's Hospital, Melbourne, has been carried out annually since 1976 . This article describes the patterns of prescribing that were observed between 1976 and 1986 with special emphasis on the results since 1980, which was the year before the adoption of the hospital's antibiotic policy . The proportion of hospital inpatients who received antibiotic therapy as determined by prevalence studies varied from 25%-36% . Since the introduction of the antibiotic policy, 61%-70% of antibiotic courses were administered for the treatment of infection and 30%-39% of the courses were administered as prophylaxis . Amoxycillin and ampicillin were prescribed most frequently, followed by the cephalosporin agents and the other penicillins . In the area of the empirical treatment of infection, compliance with the hospital antibiotic policy improved and reached 76% of courses in 1986 . In the area of prophylaxis, compliance improved a little and stood at 21% of courses in 1986. Helv Chir Acta, 1989 Jun, 56(1-2), 127 - 31 {Implantable catheter system for ambulatory parenteral antibiotic chemotherapy . A prospective study}; Laffer U et al.; 17 patients with infectious diseases needed a long-term parenteral antibiotic therapy . Therefore a subcutaneous catheter system (Port-a-Cath) was implanted for intravenous application of the antibiotic drugs . With a total dwelling-time of 952 patient/days no catheter super-infection was observed . Due to postoperative hematoma in an anticoagulated patient one catheter system was not functioning temporarily . One had to be removed on suspicion of a fungous colonization which could not be verified after bacterial examination . Quality of life for all patients was unaltered so that ambulant therapy was possible in almost 20%. Horm Metab Res, 1989 Jun, 21(6), 309 - 12 Mechanism of action of thyroxine (T4) on the biogenesis of mitochondria using antibiotic-free system: a gerontological survey; Adenuga GA et al.; For the biogenesis of mitochondria from rat liver two different genetic systems are responsible, the nucleo-cytoplasmic system, covering 85-90% of the protein, and the mitochondrial system (10-15%) . These data have been confirmed by experiment . Both protein fractions were separated by phosphate buffer (pH 11.5), in which only one of them is soluble . The experiments were performed with 3 age groups of rat: 1, 3 and 24 months . The ratio of both protein fractions was not dependent on rat age . The activities of the two genetic systems were examined by the in-vivo incorporation rate of 14 C-leucine . For the mitochondrial genetic system this rate was approximately equal in all of the age groups, while that for the nucleo-cytoplasmic genetic system was reduced in the 24 month group . Hence an age-dependence is demonstrated for the nucleo-cytoplasmic genetic system . The results of our investigation permit the conclusion that the role of the mitochondrial genetic system increases at senescence . To investigate the effect of T4 on the biogenesis of mitochondria, both protein fractions were estimated also in liver of rats treated with T4 . The result showed that there was an increase for all the age groups for protein only of nucleo-cytoplasmic origin . Since it is known that T4 stimulates the biogenesis of mitochondria and increases its protein content, it could be inferred that the action of T4 is channelled through the nucleo-cytoplasmic system independent on age, and that the nucleus plays the major regulatory role in the biogenesis of mitochondria. J Antibiot (Tokyo), 1989 Jun, 42(6), 934 - 43 Common biosynthetic feature of fortimicin-group antibiotics; Dairi T et al.; The fortimicin (FTM) group antibiotics are produced by actinomycetes belonging to various genera . FTM's and sannamycins are the products of Micromonospora olivasterospora and Streptomyces sannanensis, respectively . The possible presence of common features of the biosynthesis of these structurally related antibiotics in the two producers was examined . Enzymatic studies were done by the bioconversion experiments using FTM precursors and the washed cells of S . sannanensis . Ion pair/reverse-phase HPLC was employed as the analytical tool . S . sannanensis could convert almost all FTM precursors to the expected structures in the down stream of the pathway except one step . Thus the sets of the biosynthetic enzymes of the two bacteria share the common substrate specificity and react alternatively. J Antibiot (Tokyo), 1989 Jun, 42(6), 919 - 25 Biosynthesis and 13C NMR assignment of cytovaricin, a neutral macrolide antibiotic; Kihara T et al.; 13C NMR analysis of 13C-labeled cytovaricin which was obtained by feeding sodium {1-13C}-, {2-13C}-, and {1,2-13C}acetates, {1-13C}- and {3-13C}propionates, {1-13C}isobutyrate and {methyl-13C}methionine to cultures of Streptomyces diastatochromogenes showed that the aglycone of cytovaricin is derived from nine acetate units, six propionate units and one isobutyrate unit and the methoxy group at C-3' of cymarose moiety is derived from the methionine-S-methyl group . The 13C NMR spectra of 13C-labeled cytovaricins which were obtained from feeding experiments allowed the complete assignment of the 13C NMR spectrum of cytovaricin. Biochem Pharmacol, 1989 Jun 1, 38(11), 1755 - 62 Relationship between ionophoric and haemolytic activities of perimycin A and vacidin A, two polyene macrolide antifungal antibiotics; Cybulska B et al.; The ionophoric and hemolytic activities of two antifungal aromatic heptaenes: vacidin A and perimycin A, were studied on human red blood cells . Measurements of hemolysis, K+ influx and efflux, H+ movement and potential difference across the cell membrane, show that the hemolytic activity, being related to the K+ permeability induced by the polyene, is strongly dependent on the ability of this polyene to induce H+ movement . It was shown that: (1) both antibiotics have approximately the same efficiency in inducing K+ permeability, but a 100-fold difference in their hemolytic activity; (2) their hemolytic activity is related to their ability to induce H+ movement; (3) the protonophoric activity requires the existence of a free carboxyl group in the macrolide ring, as in vacidin A . The hemolytic activity is determined by the intrinsic efficiency of a K+/H+ exchange induced by this polyene . With perimycin A, which lacks the free carboxyl group, the hemolytic activity is dependent on the Cl- conductive flux which slows down the K+ flux. J Antibiot (Tokyo), 1989 Jun, 42(6), 837 - 45 Lanthiopeptin, a new peptide antibiotic . Production, isolation and properties of lanthiopeptin; Naruse N et al.; A strain of Streptoverticillium cinnamoneum produced a peptide antibiotic named lanthiopeptin, which contained four unusual amino acids, erythro-beta-hydroxyaspartic acid, mesolanthionine, threo-beta-methyllanthionine and lysinoalanine . Lanthiopeptin showed antiviral activity against herpes simplex virus type 1 KOS strain infection in Vero cells by cytopathic effect reduction assay . The structure of lanthiopeptin is similar to that of ancovenin. Burns, 1989 Jun, 15(3), 141 - 4 Effect of antibiotics on CR1 receptor levels of human neutrophils and on the binding and phagocytosis of opsonized polystyrene microspheres by these leucocytes; Ogle JD et al.; Fourteen antibiotics were studied for their effects on the following properties or functions of normal, human neutrophils: (1) the expression of CR1 receptors; (2) the total binding of C3b.IgG-coated polystyrene microspheres in the presence of cytochalasin D to inhibit phagocytosis; (3) the net phagocytosis of the opsonized microspheres; (4) the residual, external binding after phagocytosis . Fluorescence, flow cytometric methods were used to determine binding and phagocytosis of the model target particles . Only nafcillin, a penicillin, caused a decrease (33 per cent) in phagocytic capacity of the neutrophils at a physiologically significant dose (serum level); the antifungal antibiotic, amphotericin B, caused a 30 per cent increase in phagocytic capacity . These small changes in neutrophil phagocytic capacity may not be physiologically significant . There were no significant differences in the four measured parameters caused by other antibiotics tested at physiologically significant doses. Clin J Pain, 1989 Jun, 5(2), 177 - 81 Antibiotics and morphinomimetic injections prevent automutilation behavior in rats after dorsal rhizotomy; Suaudeau C et al.; Unilateral section of dorsal roots C5 to T1 were performed in rats, and the automutilation behavior was measured by the extent of the limb lesions expressed in arbitrary units . Changes in the scores of automutilation were studied after the injection of four substances: a morphinomimetic (pethidine) and three antibiotics, chloramphenicol, amoxicillin, and doxycycline . Effects were tested on groups of at least eight rats that were compared with another group of eight animals operated on in the same way but injected with distilled water . The animals of the group treated with pethidine performed significantly less autotomy than did the animals in the control group . The same effect was found when the animals were injected with chloramphenicol and amoxicillin . On the contrary, doxycycline was found less efficacious . These results are discussed using the hypothesis of autotomy caused by an abnormal painful sensation felt in the deafferented forelimb. G Chir, 1989 Jun, 10(6), 337 - 8 {Use of imipenem-cilastatin in antibiotic therapy and prevention in general surgery . One year of clinical experience}; Sortini A et al.; The authors report one year of clinical experience with imipenem-cilastatin, first antibiotic of thienamycin class, in the therapy and prophylaxis of postoperative infectious diseases . One hundred thirty four patients were treated with antibiotic therapy and 10 days after in 98.5% of cases a clinical remission of the disease was obtained; only in 2 patients the effect wasn't evaluable because they died for not drug-related causes . The prophylactic use of this antibiotic was limited to 34 patients with high risk of infectious diseases; only 3 cases (8.8%) showed bacterial contamination and one of them had clinical signs of disease which indicated the absolute need for antibiotic therapy . The Authors also emphasize the excellent results, the tolerability of the drug and the absence of side-effects. J Antibiot (Tokyo), 1989 Jun, 42(6), 875 - 82 Antibiotics from basidiomycetes . XXXI . Aleurodiscal: an antifungal sesterterpenoid from Aleurodiscus mirabilis (Berk . & Curt.) Höhn; Lauer U et al.; Aleurodiscal, an antifungal antibiotic has been isolated from mycelial cultures of Aleurodiscus mirabilis (Berk . & Curt.) Hohn . It causes abnormal apical branchings of Mucor miehei hyphae at very low concentrations . The structure and absolute configuration of the antibiotic has been determined by a single crystal X-ray analysis and hydrolysis to D-(+)-xylose . Aleurodiscal is a hydroxysesterterpene aldehyde beta-D-xyloside with a novel carbon skeleton. Yan Ke Xue Bao, 1989 Jun, 5(1-2), 60 - 4 The longitudinal observation of the effect of antibiotics on human tear lysozyme activity; Yang PZ et al.; It is well known that lysozyme, which catalyzes the hydrolysis of bacterial cell walls, is one of the important substances protecting the eye surface from bacterial infections . It was reported that the aminoglycoside antibiotics strongly inhibited the tear lysozyme activity . The lysozyme activity of tears which were added to different concentrations of two aminoglycoside antibiotics and three other antibiotics was determined longitudinally . No influence of any antibiotics on tear lysozyme activity was found . Therefore it is unnecessary to worry about that the use of aminoglycoside antibiotics may weaken the defence function of the eye. Br Poult Sci, 1989 Jun, 30(2), 265 - 71 Residues of aminoglycoside antibiotics in eggs after medication of laying hens; Roudaut B; 1 . The transfer of aminoglycoside antibiotics into eggs was determined separately from albumen, yolk or whole egg after oral administration of dihydrostreptomycin (DHS), neomycin and spectinomycin and after an intramuscular injection of DHS . Residues were assayed by an agar plate diffusion method in cylinders with a specific test organism for each antibiotic . 2 . Only DHS, administered by the intramuscular route, led to detectable residues in eggs . The total amount of DHS excreted via the eggs represented 1% of the dose administered . 3 . Residues in the whole egg were detected for 8 d. Eur J Biochem, 1989 Jun 1, 182(1), 181 - 6 The peptide antibiotic subtilin acts by formation of voltage-dependent multi-state pores in bacterial and artificial membranes; Schuller F et al.; The peptide antibiotic subtilin was shown to induce a rapid efflux of amino acids from intact bacterial cells and cytoplasmic membrane vesicles, and to prevent amino acid uptake by cells preincubated with the peptide . Upon addition of subtilin the trans-membrane potential (delta psi) was greatly reduced . Starved bacterial cells were less sensitive to subtilin than energized cells . Depolarization of cells by carbonyl cyanide m-chlorophenylhydrazone prevented subtilin action, but its activity could be restored by a valinomycin-induced potassium diffusion potential . Using this technique, we deduced a threshold potential of about -90 to -100 mV to be essential for subtilin action on intact cells . A similar value was obtained in macroscopic conductance measurements with black lipid membranes . The current-voltage characteristic was symmetric, i.e . subtilin induced membrane currents with trans-negative and trans-positive voltages . Single-channel experiments revealed short-lived multi-state pores of the alamethicin type . The pores had lifetimes of several hundred milliseconds and pore diameters of up to approximately 2 nm. Dent Cadmos, 1989 May 31, 57(9), 60 - 74 {Cephroxadine--a new antibiotic . Clinical experience}; Gherlone EF; Cephroxadine is an orally active cephalosporin of third generation . The most important characteristics are: 1) bacterial cell wall synthesis inhibition during active multiplication; 2) wide spectrum of action, including Gram+ and Gram- bacteria and also penicillinase and beta-lactamase producers; 3) possibility of oral administration, quick assimilation and daily moderate dosage (500 mg/12 h) . This antibiotic was tested on 71 patients to prevent and resolve dental pre-and post-operating infections . In all tested cases Cephroxadine was very effective and resolved well symptoms on second day, generally . Moreover no patient had any collateral effect to justify interruption of therapy. J Chromatogr, 1989 May 5, 490(1), 125 - 32 Determination of the aminoglycoside antibiotics sisomicin and netilmicin in dried blood spots on filter discs, by high-performance liquid chromatography with pre-column derivatization and fluorimetric detection; Tawa R et al.; A simple method for the determination of the aminoglycoside antibiotic sisomicin or its 1-N-ethyl derivative, netilmicin in whole blood, using dried blood spots (DBSs) on filter-paper punched discs has been developed . Sisomicin or netilmicin in the DBSs were recovered most effectively in 0.5 M Na2HPO4 using ultrasonication . The eluates from the DBSs were treated by ultrafiltration for deproteinization and subjected to pre-column fluorescent derivatization using o-phthalaldehyde and beta-mercaptopropionic acid in 0.05 M KH2PO4-borate buffer (pH 9.0), followed by determination by reversed-phase high-performance liquid chromatography . The detection limits of sisomicin and netilmicin in the DBSs on punched discs (10.1 microliters of whole blood) were 0.053 and 0.50 micrograms per ml of whole blood, respectively (signal-to-noise ratio greater than or equal to 2) . The method permits a simple collection of blood at the microlitre level and should prove particularly useful for monitoring sisomicin and netilmicin in blood at therapeutic levels in geriatric and paediatric patients. J Biol Chem, 1989 May 5, 264(13), 7624 - 9 Acetoacetyl-acyl carrier protein synthase . A target for the antibiotic thiolactomycin; Jackowski S et al.; The biochemical basis for the inhibition of fatty acid biosynthesis in Escherichia coli by the antibiotic thiolactomycin was investigated . A biochemical assay was developed to measure acetoacetyl-acyl carrier protein (ACP) synthase activity, a recently discovered third condensing enzyme from E . coli (Jackowski, S., and Rock, C.O . (1987) J . Biol . Chem . 262, 7927-7931) . In contrast to the other two condensing enzymes in E . coli, acetoacetyl-ACP synthase (synthase III) condensed malonyl-ACP with acetyl-CoA, rather than with acetyl-ACP . The concentration dependence of thiolactomycin inhibition of fatty acid biosynthesis in vivo was the same as the inhibition of acetoacetyl-ACP synthase activity in vitro indicating that the two phenomena were related . A thiolactomycin-resistant mutant (strain CDM5) was isolated . The specific activity of acetoacetyl-ACP synthase in extracts from this mutant was 10-fold lower than in extracts from its thiolactomycin-sensitive parent resulting in a marked defect in the ability of strain CDM5 to incorporate acetyl-CoA into fatty acids in vitro . The residual acetoacetyl-ACP synthase activity in the resistant strain was refractory to thiolactomycin inhibition . In addition, acetyl-CoA:ACP transacylase activity in strain CDM5 was resistant to inactivation by thiolactomycin suggesting that the acetoacetyl-ACP synthase also catalyzes this transacylation reaction . These data point to acetoacetyl-ACP synthase as a target for thiolactomycin inhibition of bacterial fatty acid biosynthesis. Aust N Z J Obstet Gynaecol, 1989 May, 29(2), 107 - 9 Single dose prophylactic antibiotics in caesarean sections; Chan AC et al.; A prospective, double-blind randomized trial was carried out at the Department of Obstetrics and Gynaecology, the Chinese University of Hong Kong, involving 4 groups of patients receiving a single intravenous dose of placebo, ampicillin, ampicillin and metronidazole, and ampicillin and sulbactam before operation . No difference in postoperative morbidity was present between the 4 groups of patients. Rinsho Ketsueki, 1989 May, 30(5), 768 - 73 {Antibiotics-induced agranulocytosis . Patient's IgG inhibits a GM colony formation}; Sugimoto M et al.; The pathogenesis of Cefmetazole (CMZ) induced agranulocytosis was investigated in the case of a 40-year-old man who developed agranulocytosis while he was under treatment with CMZ . Although concentration of CMZ in serum is not detected, patient's serum drawn at the time of diagnosis suppressed normal allogeneic marrow GM colonies in vitro . Normal IgG purified from serum had no effect on GM colony formation in vitro . However, patient's IgG purified from serum drawn at the time of diagnosis suppressed normal allogeneic marrow GM colony in vitro without CMZ . These studies suggest that CMZ-induced agranulocytosis is immunologically mediated through an IgG inhibitor which seems to exert its effect on GM colony formation. Pathol Biol (Paris), 1989 May, 37(5), 477 - 80 {Antibiotic and antiseptic prophylaxis in thoracic surgery . Controlled study}; Regnard JF et al.; The aim of this report was to evaluate perioperative antibiotherapy and antiseptic irrigation of the operative site in the prevention of post-pneumonectomy empyema . From 1984 to 1986, 171 patients undergoing pneumonectomy at our institution for bronchogenic carcinoma were randomly selected in 2 groups: group I (85 patients) received a "classical" prophylaxis: irrigation of the operative site with saline, plus a 7-day antibiotherapy (minocycline 200 mg/24 h) started the evening following surgery; group II (86 patients): irrigation of the operative site was performed with Povidone iodine (dilution 5%); antibiotherapy (cefotiam was given for a short period (2 g intraoperatively, 2 g 12 hours and 24 hours following surgery) . We used a "pragmatic" approach in order to choose, whatever the results would be, a type of perioperative antibiotherapy . We thus accepted the choice, without the help of statistical tests, of the therapy that would best prevent infection, and, if both regimens would demonstrate the same efficacy, to leave the choice at random . The only statistical test was to calculate the "gamma-risk" that we choose the worst among the 2 regimens . Although no significant difference in the overall infection rate was observed between the 2 groups, there were 9 empyemas (5 of those with bronchial fistula) in group I and 3 empyemas (2 of those with bronchial fistula) in group II . The cefotiam-povidone iodine regimen is thus better than the minocycline-saline regimen in the prevention of post-pneumonectomy empyema (3.5% v.s . 10.5%) . The "gamma-risk", ie the probability that the minocycline-saline regimen is the best, calculated from these percentages, is 0.03. Vrach Delo, 1989 May, (5), 109 - 12 {Professional diseases caused by the action of antibiotics}; Gerasimova MM et al.; A follow-up study is presented of the clinical aspects and pathogenesis of professional diseases due to the effect of antibiotics . A progressing, stable and regressing course of the disease was singled out . It is shown that in the long-term period the main pathogenetic mechanism was allergic vasculitis caused by penicillin, streptomycin and Candida fungi. Pharmacol Toxicol, 1989 May, 64(5), 404 - 11 Neurochemical studies on quinolone antibiotics: effects on glutamate, GABA and adenosine systems in mammalian CNS; Dodd PR et al.; Quinolone antibiotics, which can be proconvulsant in susceptible patients, were found to inhibit the specific binding of the adenosine receptor ligands L-3H-N6-phenylisopropyladenosine (L-3H-PIA) and 3H-N-ethylcarboxamidoadenosine (3H-NECA) to rat brain synaptic membranes . The inhibitions were concentration dependent, and for both ligands the order of potency was rosoxacin greater than nalidixic acid greater than oxolinic acid greater than or equal to ciprofloxacin greater than norfloxacin greater than enoxacin: IC20 values (concentrations causing a 20% inhibition of specific binding) ranged from 30-35 microM to 1-3 mM . Hill coefficients were approximately 0.5, suggesting that the compounds are probably antagonists at these sites . Most of the compounds did not alter 3H-diazepam binding directly, although rosoxacin showed relatively strong, and enoxacin weak, concentration-dependent inhibition . At 50 microM the compounds enhanced the maximal gamma-aminobutyric acid (GABA) activation of 3H-diazepam binding to varying degrees, without altering the EC50 of activation, whereas at 200 microM they tended to reduce GABA activation . Most noteworthy was the large increase in GABA-stimulated 3H-diazepam binding caused by 50 microM nalidixic acid . The compounds did not alter the Ca2+/Cl- -dependent binding of 3H-glutamate, nor of the binding of the glutamate site-selective ligands 3H-kainate and alpha-3H-amino-3-hydroxy-5-methylisoxazole-4-propionic acid (3H-AMPA); the uptake of the non-metabolized glutamate analogue D-3H-aspartate by cortical homogenates was also unaffected . The CNS side effects of these antibiotics may result, in part, from interaction with sites which mediate the inhibitory neurotransmission of adenosine and, possibly, GABA. Pharmacol Toxicol, 1989 May, 64(5), 391 - 6 Effect of antibiotics on colony formation from mouse granulocyte-macrophage progenitors (CFU-GM), megakaryocyte progenitors (CFU-M) and erythrocyte progenitors (CFU-E, BFU-E) in vitro; Maruyama T et al.; Mouse bone marrow cells were cultured in vitro in semisolid medium containing various concentrations of beta-lactam antibiotics, moxalactam (LMOX), cefotetan (CTT), flomoxef (FMOX), ceftizoxime (CTZ), cefmenoxime (CMX), cefotasime (CTX), cefamandole (CMD), cefotiam (CTM), carbenicillin (CBPC) or sulbenicillin (SBPC) . All of these antibiotics dose-dependently suppressed colony formation from granulocyte or macrophage progenitors (CFU-GM) and from megakaryocyte progenitors (CFU-M) . The suppressive potencies of these antibiotics for both progenitors, as evaluated from the drug concentrations that induced 50% suppression of colony formation (IC50), were ranked as the weakest for CBPC and SBPC, moderate for LMOX, CTT, CMX, FMOX and CTZ, and strongest for CMD, CTX and CTM . LMOX, FMOX, CTX, CBPC and SBPC also showed dose-dependent inhibition of colony formation from erythroid progenitors (CFU-E and BFU-E) . In the ranking of suppression of colony formation from CFU-E, CMD and CTX showed comparatively strong inhibition but others showed a weak effect, and in that from BFU-E, the effect was weakest for CBPC and SBPC, moderate for LMOX and FMOX, and strongest for CMD and CTX . The suppressive effect of LMOX and CMD on colony formation from each progenitor could almost be prevented by washing the cells after incubation with these antibiotics for 24 hr. Xenobiotica, 1989 May, 19(5), 567 - 79 Thiazine, antibiotic, bilirubin adducts; Eckert GM et al.; 1 . Electron charge transfer interactions of some phenothiazine derivatives with aminoglycoside antibiotics, beta-lactams and penicillin-related antibiotics and bilirubin were investigated with alternating current titrations . 2 . Neither the beta-lactams nor penicillin-related drugs interacted . 3 . However, the aminoglycoside antibiotics formed complexes with the phenothiazines . 4 . Tobramycin and gentamicin each formed 1:2 adducts with carbenicillin . 5 . The phenothiazines interacted with bilirubin forming concentration-dependent micellar adducts which were exciplexes . This may explain the appearance of xanthomata in patients medicated with phenothiazines. Ukr Biokhim Zh, 1989 May-Jun, 61(3), 117 - 9 {Antioxidant effect of the antineoplastic antibiotic obtained from a plant of the family Asteraceae}; Smirnov VV et al.; Antitumour antibiotic from a plant of the family Asteracea has been studied for the biochemical mechanism of its action . Redox processes were tested by the method of spontaneous chemiluminescence determining the intensity of freely radical oxidation of membrane cell phospholipids . It was established that the antibiotic under study stabilized the indices of spontaneous chemiluminescence up to the normal level. Antibiot Khimioter, 1989 May, 34(5), 344 - 8 {Selective medium with nalidixic acid for isolating antibiotic-producing Actinomyces}; Alferova IV et al.; The majority of actinomycetes belonging to various genera proved to be resistant to nalidixic acid concentrations having an inhibitory effect on bacteria with trailing growth i.e . B . subtilis and B . mycoides . The bacteria prevented isolation of actinomycetes as pure cultures . The use of a selective medium with nalidixic acid for isolation of soil actinomycetes resulted in 20 per cent increase in the number of the actinomycetes isolated as pure cultures . Preliminary treatment of the soil samples with calcium carbonate under moist conditions followed by the inoculation to the medium with nalidixic acid made it possible to increase isolation of actinomycetes at most 100-fold . With this complex method 495 actinomycete cultures were isolated, their antibiotic properties were studied and their taxonomic position at the genus level was determined . The complex method including the preliminary treatment of soil samples with calcium carbonate followed by inoculation to the selective medium with nalidixic acid is efficient and may be recommended for screening organisms producing new antibiotics. Rev Fr Gynecol Obstet, 1989 May, 84(5), 401 - 3 {Postoperative infection in cesarean section . Comparative study according to the antibiotic used at 2 maternity hospitals in the Central African Republic}; Kamuma M et al.; Puerperal infection is not specifically a complication seen in Africa, and the risk of infection in Europe in general, and especially in France, is not negligible . The authors report their experience, which is broad on this subject. J Anim Sci, 1989 May, 67(5), 1183 - 8 Effects of feed or water restriction, antibiotic injection and receiving diet management on commingled feeder pig performance; Brumm MC et al.; An experiment was conducted to determine the effects of 1) long-acting oxytetracycline injection at market arrival, 2) feed or water access at the auction market and 3) receiving diet management on commingled feeder pig performance . A total of 288 commingled feeder pigs transported over 1,000 km after market management treatments were used in two trials . Pigs given access to feed and water (FW) at the market weighed more (P less than .001) following marketing and transport than pigs given water only (W) . Pigs given neither feed nor water (N) were intermediate in arrival weight (19.7, 18.7 and 18.9 kg) . There was no effect (P greater than .1) of feed and water offering at the market on final weight (96.6, 95.9 and 96.6 kg), overall average daily gain (.70, .69 and .70 kg/d), overall gain/feed (.31, .31, .32) or percentage death loss (1.0, 2.1 and 4.2%) . Injection of long-acting oxytetracycline upon arrival at auction market had no effect (P greater than .1) on pig weight following marketing and transport (19.0 vs 19.2 kg), final weight (96.1 vs 97.0 kg), percentage death loss (3.4 vs 1.4%) or percentage of pigs treated (3.4 vs 4.9%) . Compared to providing ad libitum access to feed, restricting feed intake by floor feeding for the first 7 d post-arrival reduced (P less than .01) rate of gain for the first 9 d (-.04 vs . .08 kg/d), but overall there was no effect (P greater than .1) on daily gain (.70 vs .69 kg/d) or gain/feed (.31 vs .31). Orthop Nurs, 1989 May-Jun, 8(3), 35 - 8 Oral antibiotics for treatment of patients with chronic osteomyelitis; Martin ME; Enoxacin and ciprofloxacin, which are new oral quinolone derivatives, can provide an alternative treatment for patients with osteomyelitis . In the past, chronic osteomyelitis required 6-8 weeks of intravenous (IV) antibiotic therapy . These two oral antibiotics have the potential to decrease hospital days and reduce the cost of home care . Oral ciprofloxacin has been in use since the fall of 1987 . Enoxacin remains an investigational drug, and FDA approval is expected soon. Ann Plast Surg, 1989 May, 22(5), 436 - 9 Prophylactic antibiotics in surgical treatment of axillary hyperhidrosis; Ma S et al.; A randomized, prospective, double-blind study designed to compare the effectiveness of the use of cloxacillin with the result of nontreatment in patients undergoing surgical intervention of axillary hyperhidrosis was conducted from August 1987 to October 1987 at the Veterans General Hospital, Taipei, Taiwan . Forty-two patients were enrolled in this study . Fifty wounds (25 patients) were control subjects, and 34 wounds (17 patients) received cloxacillin . The positive bacterial culture rates of the tissues and draining from patients in the treatment group compared with the control group was statistically significantly lower (p less than 0.01) . No significant differences presented in relation to age, sex, complication rate, fever index, and length of hospital stay . Prophylactic antibiotic is of no value in elective surgical intervention of axillary hyperhidrosis. Orthop Rev, 1989 May, 18(5), 626 - 30, 635-7, 643-5 Works in progress #4 . Current status of local antibiotic delivery via an implantable pump; Perry CR; We present our technique and results in using an implantable drug pump to deliver antibiotics locally in the treatment of two specific orthopaedic infections: chronic recalcitrant osteomyelitis and acutely infected total joints . This method of antibiotic delivery in conjunction with appropriate surgical management results in prolonged suppression of infection in 71% of patients with chronic recalcitrant osteomyelitis . In acutely infected arthroplasties we were able to salvage the prosthesis and suppress the infection in 18 of 20 cases. J Intraven Nurs, 1989 May-Jun, 12(3), 136 - 42 Factors affecting compliance in the home i.v . antibiotic therapy client; Niederpruem MS; Home I.V . Antibiotic Therapy has been an accepted form of treatment for infections requiring parenteral forms of antibiotics since the late 1970s . Most clients successfully complete their course of therapy without complications, but for those who do not, interventions can be instituted to reach a successful completion of therapy . It takes the creativity and special skills of the I.V . Therapy nurse to overcome some of these obstacles . With proper training and identification of potential problems, most clients can finish their course of I.V . Antibiotics without incident. J Antibiot (Tokyo), 1989 May, 42(5), 752 - 60 Oxidases involved in biosynthesis of macrolide antibiotic patulolides from Penicillium urticae S11R59; Rodphaya D et al.; Patulolides are a group of 12-membered macrolide antibiotics produced by Penicillium urticae S11R59 . An enzyme involved in the conversion of patulolide C to patulolide A was purified from P . urticae S11R59 and characterized . The enzyme showed a single band on SDS-PAGE and molecular sieve HPLC both of which indicated a Mr of 86,000, indicating that the enzyme is monomeric . However, the enzyme was separated into two bands of very similar pI's (pI 4.2 and 4.3) by isoelectric focusing . Both bands catalyzed the conversion of patulolide C to patulolide A, as demonstrated by activity staining . The two isoenzymes were proved to be oxidases by the simultaneous production of H2O2 during the conversion of patulolide C to patulolide A . The molar ratio for patulolides C, A and H2O2 was determined to be 1:1:1 . The optimum pH and temperature were determined to be 7 and 35-40 degrees C, respectively, and the enzymes were stable at pH 6-9 and 4-40 degrees C . The oxidases showed characteristic absorption at 345 and 450 nm, indicating the presence of flavin as coenzyme . Among several analogues of patulolide C tested, the oxidases showed very narrow substrate-specificity; only patulolide C was oxidized to patulolide A . No enzyme activity for the reverse reaction, i.e . from patulolide A to patulolide C, was present in the cell-free extract of P . urticae S11R59 . Patulolide C oxidases therefore play a key role in the biosynthesis of patulolides. J Antibiot (Tokyo), 1989 May, 42(5), 680 - 5 New antitumor antibiotic, FR-900462 . I . Taxonomy of the producing strain; Iwami M et al.; A new species of the genus Streptomyces, the proposed name of which is Streptomyces tokashikiensis sp . nov., is described . Soil isolate, strain No . 7124, produces a new antitumor antibiotic FR-900462 . The organism is characterized by the presence of spores on the substrate hyphae . Strain No . 7124 is closely related to Streptomyces spiralis in morphological and cultural characteristics, but there are differences in spore surface, growth-permissible temperature, and carbohydrate utilization pattern . Therefore, it was decided to designate strain No . 7124 as a new species within the genus Streptomyces. J Antibiot (Tokyo), 1989 May, 42(5), 654 - 61 New glutarimide antibiotics, S-632-B1 and B2 . II . Isolation, physico-chemical properties and chemical structure; Otani T et al.; Antifungal antibiotics S-632-A1,A2,B1 and B2 were extracted with ethyl acetate from the filtered broth of Streptomyces hygroscopicus S-632 and isolated through a combination of conventional and reversed-phase silica gel column chromatography . On the basis of the spectral data, S-632-B1 and B2 were found to be new members of the glutarimide family of antibiotics . The chemical structures of these components were elucidated as two stereo-isomers of 3-(5,7-dimethyl-8,9-epoxy-2-hydroxy-4-oxo-6-decenyl)glutarimide. Arch Intern Med, 1989 May, 149(5), 1157 - 60 Home intravenous antibiotic therapy using a programmable infusion pump; Williams DN et al.; Several publications have demonstrated the efficacy, safety, and cost-effectiveness of home intravenous antibiotic therapy . The development of a computerized ambulatory infusion drug delivery pump has enabled us to treat patients previously considered ineligible for home intravenous antibiotic therapy . Seventeen patients were treated at home with the infusion pump for a range of 6 to 49 days . Selection of the infusion pump was made for a variety of reasons: the need for frequent intravenous drug administration (9 patients); impaired manual dexterity (5 patients) or cognitive function (3 patients); unwillingness to learn the necessary techniques (3 patients); and lack of support persons at home (3 patients) . Of the 17 patients, 15 could not have been discharged from hospital to home without the use of the pump or a similar device. Toxicol Appl Pharmacol, 1989 May, 98(3), 444 - 53 Toxicity and pharmacokinetics of the antibiotic fumagillin in yearling rainbow trout (Salmo gairdneri); Lauren DJ et al.; Yearling trout were administered fumagillin dicyclohexylamine (FDCH), an antibiotic that has shown promise for controlling myxozoan parasites in fish . FDCH was fed at 0.25 or 1 g/kg food at 1.5% body weight per day for 60 days, and gill, liver, kidney, spleen, thymus, intestine, and heart were examined histologically . In both treatment groups the hematopoietic tissue of the kidney and spleen was reduced and hematocrit was significantly lower relative to controls . No alteration was found in liver, intestine, heart, thymus, or gill . FDCH was also administered to trout through an indwelling catheter placed in the dorsal aorta . Plasma FDCH was measured using reverse-phase HPLC, and clearance microconstants were estimated . At the highest doses (60 and 30 mg/kg body wt) fumagillin was lethal within about 6 hr, and histological examination revealed extensive toxic alteration in liver and posterior kidney . Plasma clearance at 6 and 3 mg/kg fit a two-compartment model with a rapid alpha phase (i.e., 20 min) but a prolonged beta phase (5.4 days) . Although these fish survived for at least 96 hr, renal tubular alteration remained. Proc Natl Acad Sci U S A, 1989 May, 86(9), 3135 - 9 Multigene families for anthracycline antibiotic production in Streptomyces peucetius; Stutzman-Engwall KJ et al.; Hybridization of polyketide synthase genes from heterologous Streptomyces sp . led to the identification of four unlinked regions of DNA from Streptomyces peucetius that contain genes that encode the production of the same or closely related metabolites, some of which are intermediates of the daunorubicin pathway . DNA fragments from each region that hybridized with the heterologous polyketide synthase genes were hybridized with each other, but very little sequence similarity was observed even though at least two of the regions have similar (if not identical) functions in metabolite production . Some regions, however, do have sequence similarity with other anthracycline-producing Streptomyces sp. Pathol Biol (Paris), 1989 May, 37(5), 341 - 5 {Interpretation of the influence of immunoglobulins and glycine on bacterial sensitivity to antibiotics in vitro}; Gillissen G et al.; The effect of human immunoglobulins (Ig) and of glycine, often added to commercial preparations as a stabilizer, have been examined in vitro on the growth of E . coli strains in the absence or presence of antibiotics in subminimal inhibitory concentrations (subMic) . The Ig's (= 7S or 5S = F(ab')2 as well as glycine had no effect by themselves on bacterial growth at concentrations up to 32 mg and 4.5 mg per ml respectively . In contrast, in the presence of ampicillin, glycine induced a concentration dependent increase of bacterial sensitivity to antibiotics . This is apparently more pronounced in serosensitive than in seroresistant E . coli strains . Such a synergism could equally be shown with cefadroxil and fosfomycin, i.e . with other antibiotics interacting with cell wall synthesis, but not with those of another mode of action, as ciprofloxacin, polymyxin B or chloramphenicol. Antibiot Khimioter, 1989 May, 34(5), 337 - 43 {Ways of developing the first and second generation biocatalysts for antibiotic production}; Nys PS et al.; Methods for development of bioengineering systems of different types useful in synthesis and transformation of antibiotics are discussed . It was shown that in development of monoenzymatic biocatalysts on the basis of immobilized cells and in preparation of immobilized cultures producing secondary metabolites with enzymological engineering directed action on the cells could be provided which made it possible to establish highly efficient bioengineering systems . Various means for providing the directed action and method for estimation of the carrier-culture interation are proposed . The prospects of using the second generation biocatalysts in improvement of the processes for production of antibiotics are described. J Bacteriol, 1989 May, 171(5), 2614 - 8 Exchange of chromosomal and plasmid alleles in Escherichia coli by selection for loss of a dominant antibiotic sensitivity marker; Russell CB et al.; Transfer of an allele from a donor DNA to a recipient DNA molecule was selected by the loss of a dominant conditional lethal mutation previously incorporated ito the gene of interest in the recipient DNA . Both the Escherichia coli chromosome and plasmids carrying E . coli genes were used successfully as donor molecules . Recipient molecules for these exchanges were constructed in vitro by using the rpsL gene, which confers sensitivity to streptomycin, to replace segments of specific E . coli genes located either on multicopy plasmids or in the E . coli chromosome . Plasmids carrying such replacements were capable of acquiring chromosomal alleles of the gene(s) of interest, and strains carrying rpsL replacements in the chromosome were capable of acquiring plasmid-encoded alleles at the sight of the rpsL replacement . In both situations, these allele transfers resulted in loss of the rpsL gene from the recipient DNA molecule . The desired transfer events constituted a large percentage of these events, which gave rise to viable colonies when appropriate donor-recipient pairs were subjected to streptomycin selection . Thus, this is a useful approach for transferring alleles of interest from plasmids to the E . coli chromosome and vice versa. J Gen Microbiol, 1989 May, 135 ( Pt 5), 1071 - 81 Use of a fractionated coupled transcription-translation system in the study of ribosomal resistance mechanisms in antibiotic-producing Streptomyces; Calcutti MJ et al.; The coupled transcription-translation system, formerly involving extracts of Streptomyces lividans, has been developed such that it functions with ribosomes (or their subunits) from at least 20 different Streptomyces species . This fractionated system has been used to investigate the antibiotic responses of ribosomes from various Streptomyces which synthesize inhibitors of protein synthesis . Of the 11 organisms included in this study, two strains possessed ribosomes that were specifically resistant to the autogenous antibiotic . These were Streptomyces pactum and Streptomyces karnatakensis, both of which produce pactamycin . Ribosomal subunit exchange analysis further demonstrated that resistance to pactamycin in those strains is due to some property of the 30S ribosomal subunits. Pharm Res, 1989 May, 6(5), 387 - 93 Kinetics of the aspartyl transpeptidation of daptomycin, a novel lipopeptide antibiotic; Kirsch LE et al.; Two degradation products of the lipopeptide antibiotic, daptomycin, were identified and the reaction pathway and kinetics were delineated in aqueous solution at 60 degrees C, pH range 3 to 8 and ionic strength 0.01 . The degradation products were 1) a succinimido intermediate (anhydro-daptomycin) formed by attack of side-chain carbonyl on the peptide-bond nitrogen in the asp-gly sequence and 2) a beta-asp daptomycin isomer formed by rehydration of the anhydrodaptomycin succinimide . This aspartyl transpeptidation pathway was found to be reversible . Formation of the anhydrodaptomycin from either daptomycin or beta-asp daptomycin was pH dependent but the pH-rate profiles for anhydrodaptomycin formation were not mechanistically interpretable . The pH-rate profiles for the formation of daptomycin or beta-asp daptomycin from the anhydrodaptomycin were linear with slopes = 1, which is consistent with nucleophilic hydroxide ion attack of the succinimido intermediate at either the alpha-carbonyl, giving rise to the beta-asp daptomycin, or the beta-carbonyl, giving rise to daptomycin. J Antibiot (Tokyo), 1989 May, 42(5), 761 - 8 Mechanism of activation of the antitumor antibiotic neocarzinostatin by mercaptan and sodium borohydride; Hensens OD et al.; The structures of mercaptan and sodium borohydride reaction products of neocarzinostatin chromophore A (NCS Chrom A) are compared . Implications on the mechanism of activation of NCS are discussed. J Antibiot (Tokyo), 1989 May, 42(5), 667 - 73 Mureidomycins A-D, novel peptidylnucleoside antibiotics with spheroplast forming activity . II . Structural elucidation; Isono F et al.; Structures of new antibiotics, mureidomycins (MRD's) A approximately D, were deduced from spectroscopic analyses and degradation studies . Two residues of m-tyrosine, one residue of 2-amino-3-N-methylaminobutyric acid (AMBA) and methionine are present in all components of the complex . Uracil is contained in MRD's A and C, while dihydrouracil in MRD's B and D . Methionine and m-tyrosine are connected through an ureido bond, and uracil or dihydrouracil is linked to AMBA via enamine sugar moiety . In addition, MRD's C and D contain a glycine residue at the N-terminal. Brain Res, 1989 Apr 17, 485(1), 62 - 6 Cholecystokinin antagonism by anthramycin, a benzodiazepine antibiotic, in the central nervous system in mice; Kubota K et al.; Anthramycin (ATM) which is a product of some streptomyces micro-organisms was shown to antagonize the central effects of cholecystokinin (CCK) such as antinociception and satiety and to displace CCK bound to the slices from the brains of mice . Sulfated octapeptide CCK (CCK8) was administered intracisternally to mice at doses of 1 microgram/mouse for inducing antinociception and 200 ng/mouse for satiety . ATM was administered intraperitoneally to mice at doses such as 0.3 and 0.5 mg/kg . CCK8-induced antinociception and satiety were significantly reversed by ATM in those doses . {125I}CCK8 binding to the brain slices was observed autoradiographically . The autoradiograms from the slices were converted to false color images by using a microcomputer . The radioactivity in the autoradiograms was expressed by color spectra in the false color images . Comparison of the binding of {125I}CCK8 to the brain slices in the presence and the absence of ATM revealed that ATM (10(-6) M) clearly displaced the CCK8 binding in the various regions, especially in the cortex, of the brain . These findings suggest that ATM acts as an potent antagonist of CCK in the central nervous system in mice. Biochem J, 1989 Apr 15, 259(2), 433 - 41 Interaction of the antitumour antibiotic luzopeptin with the hexanucleotide duplex d(5'-GCATGC)2 . One-dimensional and two-dimensional n.m.r . studies; Searle MS et al.; 1H- and 31P-n.m.r . spectroscopy were used to characterize the solution structure of the 1:1 complex formed between the antitumour antibiotic luzopeptin and the self-complementary hexanucleotide d(5'-GCATGC)2 . Eighteen nuclear Overhauser effects between antibiotic and nucleotide protons, together with ring-current-induced perturbations to base-pair and quinoline 1H resonances, define the position and orientation of the bound drug molecule . Luzopeptin binds in the minor groove of the DNA with full retention of dyad symmetry, its quinoline chromophores intercalating at the 5'-CpA and 5'-TpG steps and its depsipeptide ring spanning the central two A.T base-pairs . The chromophores stack principally on the adenine base with their carbocyclic rings pointing towards the deoxyribose of the cytosine . There is no evidence for Hoogsteen base-pairing in the complex, all glycosidic bond angles and sugar puckers being typical of B-DNA as found for the free hexanucleotide . The 'breathing' motions of the A.T and internal G.C base-pairs are substantially slowed in the complex compared with the free DNA, and the observation that two phosphate resonances are shifted downfield by at least 0.5 p.p.m . in the 31P-n.m.r . spectrum of the complex suggests pronounced local helix unwinding at the intercalation sites . The data are consistent with a model of the complex in which luzopeptin bisintercalates with its depsipeptide essentially in the conformation found in the crystal of the free antibiotic {Arnold & Clardy (1981) J . Am . Chem . Soc . 103, 1243-1244} . We postulate only one conformational change within the peptide ring, which involves rotation of the pyridazine-glycine amide group linkage by 90 degrees towards the DNA surface . This manoeuvre breaks the glycine-to-glycine transannular hydrogen bonds and enables the glycine NH groups to bond to the thymine O-2 atoms of the sandwiched A.T base-pairs . It also shortens the major axis of the depsipeptide so that the interchromophore distance is more suitable for spanning two base-pairs . The model further implies that the carboxy and hydroxy groups of the L-beta-hydroxyvaline residue are appropriately positioned for hydrogen-bonding to the 2-amino group of guanine and the O-2 atom of cytosine of the adjacent G.C base-pair. FEBS Lett, 1989 Apr 10, 247(1), 17 - 21 Spontaneous polymerization of the antibiotic peptide magainin 2; Urrutia R et al.; We describe here the ability of the magainin 2 peptide to assemble spontaneously into characteristic 13-nm diameter filaments having a 30 nm periodic helical substructure . Optimal conditions for extensive polymerization into filaments of several hundred microns required low pH and high ionic strength . Polymerization of the magainin 2 peptide may be involved in its recently described in vitro membrane-disrupting and antibiotic activities. Am J Surg, 1989 Apr, 157(4), 410 - 2 Altered pharmacokinetics of antibiotics during vascular surgery; Guglielmo BJ et al.; Prophylactic antibiotics significantly decrease the incidence of infection in various surgical procedures . Although antibiotics must be administered preoperatively to be effective, it is unknown whether therapeutic concentrations are necessary throughout the operation to prevent infection . Furthermore, the pharmacokinetics of antibiotics during surgical procedures is not well understood . Several factors, including blood loss, fluid redistribution, and changes in renal blood flow may alter the pharmacokinetic disposition of the antibiotic . In a controlled investigation of intraoperative antibiotic pharmacokinetics, cefamandole was studied in eight patients undergoing elective surgery of the abdominal aorta and peripheral vasculature . Both elimination half-life (67 +/- 19 minutes versus 93 +/- 23 minutes) and the volume of distribution (16.8 +/- 5.3 liters versus 25.2 +/- 11.9 liters) increased when compared with the preoperative state . The increased volume may be due, in part, to redistribution of fluid . Plasma concentrations of antibiotic were low at the time of graft placement in those patients with normal renal function . Additional antibiotic dosing may be warranted prior to prosthesis insertion in these patients. Am J Med, 1989 Apr, 86(4), 442 - 8 The nonvalue of retrospective peer comparison feedback in containing hospital antibiotic costs; Parrino TA; Antibiotics have accounted for an increasing percentage of hospital pharmacy charges . Recently, an inexpensive method, automated peer comparison feedback, has been developed to influence physician use of resources . The documented success of several implementations of this strategy led to a one-year experiment to influence hospital antibiotic utilization . Each month, attending physicians in the top 50 percentiles for expenditure were notified of their status in relation to their peers . Expenditures by feedback and control groups were compared to determine whether feedback would result in reduced expenditures by individuals, or whether there would be a generalized reduction in expenditure by the entire group (Hawthorne effect) . Over the year, no significant reduction in expenditure was noted . However, some important utilization patterns were identified . Although more surgical patients received antibiotics than did nonsurgical patients, surgical antibiotic costs were less . Surgical therapy was typically of shorter duration and involved the use of less expensive antibiotics . Multiple-antibiotic prescribing was less frequent on surgical services . Thirty percent of attending physicians were responsible for 80 percent of all antibiotic costs; 60 percent of those in this top group were members of the medical cohort . In conclusion: (1) As implemented in the current study, automated peer comparison feedback was not an effective method for reducing antibiotic utilization; (2) Differences in prescribing patterns between services may dictate the best strategies for improving antibiotic utilization; (3) More attention should be directed toward the relatively small "reference group" of physicians responsible for most hospital antibiotic prescribing. Fundam Appl Toxicol, 1989 Apr, 12(3), 558 - 66 Investigations of the potential for five beta-lactam antibiotics to elicit type II hypersensitivity reactions in rats and monkeys; Kornbrust D et al.; Immunologic reactions are occasionally elicited in patients by various beta-lactam antibiotics (e.g., penicillins and cephalosporins) . A relatively rare reaction (type II hypersensitivity) may involve antibody-mediated destruction of erythrocytes, leukocytes, and/or platelets . During the safety evaluation of several modified beta-lactam compounds (carbapenems), hemolytic anemia and/or neutropenia were observed in rhesus monkeys, and anemia, neutropenia, and thrombocytopenia in rats, after approximately 2 weeks of intravenous administration . Antiglobulin tests and other clinicopathologic findings indicated an immune basis for the cytopenias . A review of summaries of the preclinical data for numerous marketed beta-lactam antibiotics revealed that various cytopenias of unknown etiology were commonly seen in animals given high doses of these compounds . To determine whether these hematologic abnormalities were related to those produced by the above carbapenems, we investigated the potential of five widely used beta-lactam antibiotics (penicillin G, cephalothin, cefazolin, cefoperazone, and cefamandole) to elicit immune-mediated cytopenias in rhesus monkeys and Sprague-Dawley rats when given intravenously . After approximately 1 month of administration of these compounds at a dose level of 500 mg/kg/day, slight anemia occurred in several drug-treated monkeys; however, direct and indirect antiglobulin tests were negative for all animals, indicating that the anemias were not immune-mediated . In rats, no drug-induced hematologic changes were observed after 1 month of intravenous administration of 500 and 1000 mg/kg/day of each of the beta-lactams . In addition, direct antiglobulin tests were negative in rats . Therefore, it appears that the ability of certain carbapenem antibiotics to produce a high incidence of type II hypersensitivity reactions in animals is not typical of beta-lactam compounds in general. FEMS Microbiol Lett, 1989 Apr, 49(2-3), 263 - 7 Structural gene isolation and prepeptide sequence of gallidermin, a new lanthionine containing antibiotic; Schnell N et al.; Peptide antibiotics containing lanthionine and 3-methyllanthionine bridges, named lantibiotics are of increasing interest . A new lantibiotic, gallidermin, has been isolated from Staphyloccus gallinarum . Here we report the isolation of its structural gene which we name gdmA . In all lantibiotics so far studied genetically, three peptides can be formally distinguished: (i) the primary translation product, which we call the prepeptide; (ii) the propeptide lacking the leader sequence and (iii) the mature lantibiotic . Unlike the plasmid-coded epidermin, gdmA is located on the chromosome . The gdmA locus codes for a 52 amino acid residue prepeptide, consisting of an alpha-helical leader sequence of hydrophilic character, which is separated from the C-terminus (propeptide) by a characteristic proteolytic processing site (Pro-2 Arg-1 Ile1) . Although pro-gallidermin differs from pro-epidermin (a recently isolated lantibiotic) only by a single amino acid residue exchange . Leu instead of Ile, the N-terminus of the prepeptide differs by an additional two exchanges. J Biochem (Tokyo), 1989 Apr, 105(4), 606 - 10 A deacylation enzyme for aculeacin A, a neutral lipopeptide antibiotic, from Actinoplanes utahensis: purification and characterization; Takeshima H et al.; An enzyme, tentatively termed aculeacin A acylase, useful in preparing deacylated peptides which are used as starting material for semisynthetic antifungal antibiotics, was purified from the culture filtrate of Actinoplanes utahensis NRRL12052 . The purification involved ultrafiltration and column chromatographies on DEAE-cellulose, hydroxyapatite, and Butyl-Toyopearl 650M . The purified enzyme was composed of two dissimilar subunits with molecular weights of 55,000 and 19,000 . The subunits were dissociated in the presence of 0.1% SDS or 6 M guanidine hydrochloride; the dissociation accompanied loss of acylase activity . The enzyme was fully active at pH 7.0 and at 60 degrees C . Its pI was estimated to be above 10.25 . The Km and Vmax for aculeacin A were 1.53 mM and 39.7 mumol/min/mg-protein, respectively. Antibiot Khimioter, 1989 Apr, 34(4), 294 - 8 {Accumulation of gentamicin in biological fluids, organs and tissues during regional lymphotropic therapy with antibiotics}; Buianov VM et al.; Gentamicin distribution in biological fluids, organs and tissues, lymph nodes was studied on 70 dogs . Three administration routes were compared: lymphotropic, intramuscular and regional subcutaneous . The lymphotropic route for the drug administration was recommended not long ago . It was shown that the lymphotropic route provided the antibiotic accumulation mainly in some of the abdominal organs as compared to intramuscular administration . Regional lymphotropic administration of the antibiotic to the experimental animals resulted in higher gentamicin levels in the regional lymph nodes and regional organs as compared to the levels observed after the antibiotic regional subcutaneous administration in the same doses. Antibiot Khimioter, 1989 Apr, 34(4), 254 - 8 {The structure of eremomycin, a new antibiotic of the group of polycyclic glycopeptides}; Lomakina NN et al.; Structure of the carbohydrate moiety of the eremomycin molecule was assessed . Two residues of eremosamine were detected in the antibiotic . One of them in the composition of 2-0-(L-eremosaminyl)-D-glucopyrazone dissaccharide was linked by the phenol group to monodechlorvancomycinic acid and the other formed the monosaccharide branch by the alcohol group of the same acid at the peptide C-end area . On the basis of the results of the present study and the data published earlier (structure of the aglycone and aminosugar) the structure of eremomycin was assigned. J Dairy Sci, 1989 Apr, 72(4), 1057 - 62 Effectiveness of intramammary antibiotic therapy based on somatic cell count; Seymour EH et al.; The Virginia Tech dairy herd was used in a 10-mo study to determine the effect of intramammary antibiotic therapy of quarters with elevated SCC on milk production, subsequent DHIA SCC, and infection status . Cows were assigned randomly to experimental or control groups . Animals in both the control and experimental groups with SCC scores greater than or equal to 5 for the first time during that lactation were quarter sampled, milk was cultured to detect presence of mastitis pathogens, and SCC was determined . All experimental cows with quarter SCC greater than or equal to 5 were treated with an intramammary cephapirin product only in those elevated quarters (DHIA SCC greater than or equal to 5), regardless of clinical symptoms . Control cows received antibiotic therapy when symptoms were clinical, regardless of SCC . Treatment group had no significant effect on milk production, SCC, or infection status of the cow . Treatment of cows in the experimental group cured 70% of infected quarters, whereas only 50% of infections in the control group were eliminated. Antimicrob Agents Chemother, 1989 Apr, 33(4), 452 - 9 Reactions catalyzed by purified L-glutamine: keto-scyllo-inositol aminotransferase, an enzyme required for biosynthesis of aminocyclitol antibiotics; Lucher LA et al.; Dialyzed extracts of the gentamicin producer Micromonospora purpurea catalyze reactions which represent transaminations proposed for 2-deoxystreptamine biosynthesis . To determine whether these transaminations were catalyzed by a single aminotransferase or by multiple enzymes, we purified and characterized an L-glutamine:keto-scyllo-inositol aminotransferase from M . purpurea . This enzyme was purified 130- to 150-fold from late-log-phase mycelia of both wild-type M . purpurea and a 2-deoxystreptamine-less idiotroph . The cofactor pyridoxal phosphate was found to be tightly bound to the enzyme, and spectral analysis demonstrated its participation in the transamination reactions of this enzyme . The major physiological amino donor for the enzyme appears to be L-glutamine; the keto acid product derived from glutamine was characterized as 2-ketoglutaramate, indicating that the alpha amino group of glutamine participates in the transamination . We found that crude extracts contained omega-amidase activity, which may render transaminations with glutamine irreversible in vivo . The substrate specificity of the aminotransferase was shown to be restricted to deoxycyclitols, monoaminocyclitols, and diaminocyclitols, glutamine, and 2-ketoglutaramate, which contrasts with the broader substrate specificity of mammalian glutamine aminotransferase . The appearance of the enzyme in late-log phase, coupled with its narrow substrate specificity, indicates that it participates predominantly in 2-deoxystreptamine biosynthesis rather than in general metabolism . The enzyme catalyzes reactions which represent both transamination steps of 2-deoxystreptamine biosynthesis . Although copurification of two aminotransferases cannot be ruled out, our data are consistent with the participation of a single aminotransferase in the formation of both amino groups of 2-deoxystreptamine during biosynthesis by M . purpurea . We propose that this aminotransferase participates in a key initial step in the biosynthesis of most aminocyclitol antibiotics. Antimicrob Agents Chemother, 1989 Apr, 33(4), 418 - 23 Influence of antibiotic dose, dosing interval, and duration of therapy on outcome in experimental pneumococcal meningitis in rabbits; Tauber MG et al.; We examined the influence of several pharmacokinetic parameters on cure rates in rabbits with experimental pneumococcal meningitis . When the duration of treatment was kept constant, cure rates improved as the individual dose of ampicillin was increased . On the other hand, when four doses of ampicillin at 60 mg/kg of body weight, producing peak concentrations in cerebrospinal fluid (CSF) of approximately 40 times the MBC, were administered at intervals of 24 instead of 4 h and the duration of therapy was thus prolonged from 12 to 72 h, cure rates also increased (85 versus 25%; P less than 0.01) . These high cure rates were achieved even though bacterial titers in CSF 24 h after the first dose had reached levels similar to those present at the beginning of therapy . Cure in these animals was explained by the fact that the second ampicillin dose reduced bacterial titers in CSF significantly more than did the first dose (5.2 versus 2.5 log10 CFU/ml; P less than 0.02) . The clinical relevance of these observations remains to be determined. J Antibiot (Tokyo), 1989 Apr, 42(4), 577 - 84 Production of new polyene antibiotics by Streptomyces cellulosae after addition of ethyl (Z)-16-phenylhexadec-9-enoate; Li Z et al.; Ethyl (Z)-16-phenylhexadec-9-enoate (3), an analog of ethyl oleate (2), was synthesized and added to cultures of Streptomyces cellulosae ATCC 12625 which normally produce fungichromin (1) as the principal polyene antibiotic . These cultures showed drastic reduction of fungichromin biosynthesis but afforded four new polyene antibiotics with a truncated four carbon side chain which are designated as isochainin (11) (an isomer of chainin (10}, 14-hydroxyisochainin (12), 1'-hydroxyisochainin (13), and 1',14-dihydroxyisochainin (14) . The close correspondence of 13C NMR chemical shifts between these compounds and fungichromin suggests that the stereochemistry at every site is exactly analogous. J Biomed Mater Res, 1989 Apr, 23(4), 379 - 97 Influence of antibiotic impregnation on the fatigue life of Simplex P and Palacos R acrylic bone cements, with and without centrifugation; Davies JP et al.; The fatigue properties of Simplex P and Palacos R bone cements were compared to their antibiotic impregnated counterparts AKZ* and Palacos R with gentamycin . The effect of porosity reduction by centrifugation of all four cement types was also assessed . Fifteen specimens of each cement type were prepared according to manufacturer's instructions and 15 additional specimens of each cement type were prepared by mixing the powder with chilled monomer (0 degrees C) and then centrifuging the cement immediately after mixing . Fifteen fully reversed tension-compression fatigue tests were performed at 15 MPa in stress control for each cement preparation in vitro while simulating the in vivo state (37 degrees C and 100% humidity) . The number of cycles to failure were recorded . There was no significant difference in the fatigue life of Palacos R and Simplex P when both cements were prepared in the standard fashion . The addition of 1/2 g of gentamycin to Palacos R did not significantly alter its fatigue properties . The addition of 0.5 g of erythromycin and 0.24 g of colistin did not decrease the fatigue life of Simplex P . Centrifugation significantly improved the fatigue properties of Simplex P and AKZ . The fatigue lives of Palacos R and Palacos R with gentamycin were not improved by centrifugation . The fatigue life of centrifuged Simplex P was significantly greater than the fatigue life of Palacos R and of Palacos R with gentamycin, whether the Palacos R based cements were centrifuged or not. Biochem Pharmacol, 1989 Apr 1, 38(7), 1121 - 4 Phenylazoxycyanide damages microtubular protein more than its reference antibiotic, calvatic acid; Gadoni E et al.; The effect of phenylazoxycyanide and calvatic acid, its reference antibiotic, on some functions of tubulin obtained from different sources has been studied . Our purpose was to establish a possible correlation between the antitumour activity of these drugs and their antimicrotubular action . Microtubules are subcellular structures involved in proliferation and maintenance of the cell shape and probably in malignant transformation; indeed most antimitotic drugs influence the stability of microtubules through the interaction with tubulin, their main protein . In this work we found phenylazoxycyanide impairs, more than calvatic acid, polymerization of purified tubulin from calf brain . It also damages, in a dose-dependent manner, colchicine-binding ability of tubulin derived from rat liver and AH-130 Yoshida ascite hepatoma cells . Compounds displaying an azoxycyano group may represent new antimicrotubular agents and their effect could be modulated by the different polarity and structural characteristic of the molecule. Arch Stomatol (Napoli), 1989 Apr-Jun, 30(2), 307 - 28 {Use of antibiotics during periodontal disease}; Caruso F et al.; Authors consider the possibility to use antibiotics to control periodontal disease . More used antibiotics are exposed systematically and topically administered. Antimicrob Agents Chemother, 1989 Apr, 33(4), 535 - 40 Minimum antibiotic levels for selecting a resistance plasmid in a gnotobiotic animal model; Corpet DE et al.; The minimum antibiotic concentrations for selecting an R plasmid in vivo were determined in germfree mice colonized by two isogenic strains of Escherichia coli, one of which carried an R plasmid . Seventy groups of three gnotobiotic mice were given low doses of ampicillin, colistin, flumequin, gentamicin, tetracycline, or streptomycin via drinking water for 2 weeks . The equilibrium between susceptible and resistant populations of bacteria was monitored daily in feces and compared with that of control mice given pure water . This model yielded reproducible data, and dose and response were strongly correlated . The minimum selecting doses ranged from 0.9 to 12.8 micrograms/ml of water, depending on the antibiotic and the R plasmid . The use of mathematical models and complementary in vitro experiments accounted for the effect of the low antibiotic levels. J Antibiot (Tokyo), 1989 Apr, 42(4), 604 - 10 Inhibition of c-myc gene expression in murine lymphoblastoma cells by geldanamycin and herbimycin, antibiotics of benzoquinoid ansamycin group; Yamaki H et al.; We have shown that geldanamycin (GDM), an antibiotic of benzoquinoid ansamycin group, inhibits DNA replication in cultured mouse lymphoblastoma L5178Y cells . Here we report that GDM selectively inhibited the expression of c-myc gene, proto-oncogene, along with suppression of DNA replication in L5178Y cells, which are consistent with our previous results that c-myc protein promotes cellular DNA replication . The significantly enhanced inhibition by GDM of DNA replication was observed, when the antibiotic was introduced at G1 stage prior to S phase of cell cycle . The results are in favor of the prospects that GDM inhibits DNA replication mainly at time of initiation, and that c-myc protein is essential for the initiation of cellular DNA replication . Furthermore, when c-myc expression was inhibited by GDM, the expression of p53 gene, the product of which may be another DNA replication protein, was stimulated in the tumor cells . Thus, GDM should be useful to investigate the molecular mechanism of DNA replication promoted by c-myc protein and also to distinguish the function of c-myc protein from that of p53 protein in DNA replication. Am J Surg, 1989 Apr, 157(4), 443 - 9 Antibiotic beads in the management of surgical infections; Calhoun JH et al.; Polymethyl methacrylate antibiotic beads have been used successfully in the treatment of surgical infections . Presented are their mechanism of action, their use in experimental and clinical settings, and their complications. J Antibiot (Tokyo), 1989 Apr, 42(4), 549 - 52 A new antitumor antibiotic, FR900840 . II . Structural elucidation of FR900840; Nishimura M et al.; The structure of FR900840, a new antitumor antibiotic produced by a strain of Streptomyces has been deduced as 1 on the basis of spectroscopic and chemical evidence and finally confirmed by synthesis from L-threonine and L-serine. J Antibiot (Tokyo), 1989 Apr, 42(4), 542 - 8 A new antitumor antibiotic, FR900840 . I . Discovery, identification, isolation and characterization; Nishimura M et al.; A new antitumor antibiotic, FR900840, was isolated from a culture broth of Streptomyces strain No . 8727 as a pale yellowish prism and the molecular formula was determined to be C7H11N3O5 . The antibiotic exhibited prominent antitumor effects on human tumor cell lines both in vitro and in vivo. EMBO J, 1989 Apr, 8(4), 1213 - 6 Mutations in 16S ribosomal RNA disrupt antibiotic--RNA interactions; De Stasio EA et al.; Two of six mutations at a base-paired site in Escherichia coli 16S rRNA confer resistance to nine different aminoglycoside antibiotics in vivo . Chemical probing of mutant and wild-type ribosomes in the presence of paromomycin indicates that interactions between the antibiotic and 16S rRNA in mutant ribosomes are disrupted . The altered interactions measured in vitro correlate precisely with resistance seen in vivo and may be attributable to specific structural changes observed in the mutant rRNA. FEBS Lett, 1989 Mar 13, 245(1-2), 145 - 9 Modelling basic features of specificity in DNA-aureolic acid-derived antibiotic interactions; Chen KX et al.; The nonintercalative groove binding of a simplified model of olivomycin, to sequences d(CGCGCGC)2, d(TATATAT)2, and d(CICICIC)2 is investigated . A significant preference is displayed for the minor groove of the d(CG) sequence . This is due predominantly to the formation of H-bonds between the hydroxyl groups on the aglycone of the drug and the 2-amino group of the central guanine of the oligonucleotide. Biochem Pharmacol, 1989 Mar 1, 38(5), 795 - 802 Oxidative and mitochondrial toxic effects of cephalosporin antibiotics in the kidney . A comparative study of cephaloridine and cephaloglycin; Tune BM et al.; Cephaloridine and cephaloglycin are the two most nephrotoxic cephalosporins released for human use . Cephaloridine has been shown to produce both oxidative and mitochondrial respiratory injury in renal cortex in patterns of dose (or concentration) and time that are consistent with pathogenicity . Cephaloglycin also produces respiratory toxicity, and recent studies have provided evidence that this injury results from an inactivation of mitochondrial anionic substrate transporters . The abilities of cephaloglycin to produce oxidative changes and cephaloridine to block mitochondrial substrate uptake have not been examined yet . We therefore compared these two cephalosporins with one another and with cephalexin, which is not nephrotoxic, in the production of the following: (1) several components of oxidative stress or damage {depletion of reduced glutathione (GSH) and production of oxidized glutathione (GSSG) in renal cortex, inhibition of glutathione reductase in vitro, and production of the lipid peroxidation products malondialdehyde (MDA) and conjugated dienes (CDs) in renal cortex}; and (2) renal cortical mitochondrial toxicity {to both respiration with, and the transport of, succinate} . Cephaloridine depleted GSH and elevated GSSG in renal cortex, inhibited glutathione reductase, and increased both MDA in whole cortex and CDs in cortical microsomes and mitochondria . While cephaloglycin depleted GSH at least as much as did cephaloridine, it produced one-fifth as much GSSG and had little or no effect on glutathione reductase activity or on cortical MDA or microsomal CDs; cephaloglycin caused a transient small increase of mitochondrial CDs . Cephalexin produced no oxidative changes except for a slight increase of mitochondrial CDs comparable to that produced by cephaloglycin . Both cephaloridine and cephaloglycin, but not cephalexin, decreased the unidirectional uptake of, and respiration with, succinate in cortical mitochondria . We conclude that cephaloridine and cephaloglycin are both toxic to mitochondrial substrate uptake and respiration, but differ significantly in their generation of products of oxidation. Arch Ophthalmol, 1989 Mar, 107(3), 439 - 40 The effects of freezing and antibiotics on the viability of Acanthamoeba cysts; Matoba AY et al.; The effects of cryotherapy and antibiotics (paromomycin, neomycin, or propamidine isethionate) on the viability of Acanthamoeba polyphaga and Acanthamoeba castellani cysts were studied in vitro . Either cryotherapy or exposure to antibiotic led to a decrease in the number of viable A castellani detected; A polyphaga showed variable response to the antibiotics tested . The combination of cryotherapy and antibiotic therapy was more cysticidal than either modality alone and eliminated detectable viable organisms in five of six experiments . Of the antibiotic solutions tested, paromomycin (15 mg/mL) was the most effective. Mutat Res, 1989 Mar, 211(1), 171 - 80 4-Quinolone antibiotics: positive genotoxic screening tests despite an apparent lack of mutation induction; Bredberg A et al.; The effects of different 4-quinolone antibiotic derivatives (4-Qs) in a number of short-term tests commonly employed for the evaluation of genetic toxicity were studied . Incorporation of {3H}thymidine into mitogen-stimulated peripheral blood lymphocytes was strongly enhanced at a low concentration (1.56 micrograms/ml) for most of the tested 4-Qs, whereas DNA strand breakage in lymphoblastoid cells was evident only for ciprofloxacin (10 micrograms/ml and upwards), ofloxacin (80 micrograms/ml) and norfloxacin (160 micrograms/ml) . Ciprofloxacin induced a significant amount of unscheduled DNA synthesis, but was found to be negative in a shuttle vector plasmid mutation test . Ciprofloxacin (80 micrograms/ml) did not inhibit enzymes involved in the early steps of pyrimidine biosynthesis . Cell growth was slightly depressed at a concentration of 20 micrograms/ml, becoming marked at 80 micrograms/ml . In conclusion, this study seeks to contribute to an improved evaluation of genotoxic screening test data, by focusing attention on the conflicting effects imposed by the 4-Qs on a battery of such tests. Vopr Virusol, 1989 Mar-Apr, 34(2), 197 - 200 {The search for antibiotics not exerting activating action in the persistence of the tick-borne encephalitis virus}; Malenko GV et al.; Chronic tick-borne encephalitis (TBE) frequently develops in the presence of concomitant diseases requiring antibiotic therapy . Because some antibiotics, e.g . streptomycin, strongly activate persisting TBE virus, a study was carried out in search of antibiotics without the activating effect . The experiments were carried out in Syrian hamsters inoculated subcutaneously with the Vasil'chenko strain of TBE virus which at 60-348 days of the persistent infection were given florimycin, levomycetin and kanamycin . The antibiotics were administered for 3 weeks . Levomycetin showed no activating properties, while kanamycin and florimycin exerted weak activating effect on the persisting TBE virus (isolated from 5% of the specimens) without marked immunosuppressive effect or manifestation of the infection . The TBE virus strains isolated on the 205th day from the brain and 348th day from the spleen of the hamsters given kanamycin and florimycin had higher virulence than the original strain. Antibiot Khimioter, 1989 Mar, 34(3), 180 - 6 {Effect of plasmid pIJ350 on genetic stability of antibiotic production by Streptomyces bambergiensis}; Zotchev SB et al.; It was shown that S . bambergiensis S800 was genetically instable with respect to the property of the antibiotic production (Ant) while in strain S712 of S . bambergiensis this property was stable . Transformation of S . bambergiensis protoplasts with pIJ350 plasmid DNA and analysis of the transformants screening revealed induction of the Ant instability in both the strains . In case of plasmids pVG101 and pIJ943 this effect was not shown . Analysis of the S800 (pIJ350) transformant screening revealed five groups of mutants differing in the antibiotic production level and the presence of pIJ350 plasmid . Restriction analysis of the total DNA of the mutants showed that there were large deletions in the genome of two of them . Retransformation of the mutants with pIJ350 plasmid DNA showed that in all the cases induction of the instability was lacking . The behaviour of the spontaneous mutants Ant- of strain S800 with respect to pIJ350 plasmid was analogous to that of the mutants Ant- from the transformant S800 (pIJ350) screening . A hypothetic model for the determinant incompatibility with pIJ350 plasmid genetically linked to the Ant property in the genome of S . bambergiensis and unstable in strain S800 was proposed. Antibiot Khimioter, 1989 Mar, 34(3), 216 - 7 {Cytogenetic effect of the antineoplastic anthracycline antibiotic 4'-epidoxorubicin}; Nerseian AK et al.; Cytogenetic action of 4'-epidoxorubicin (farmorubicin), an antitumor antibiotic was studied with using rat bone marrow cells . It was shown that after intraperitoneal administration the antibiotic increased the number of the aberrant metaphases when the dose was not lower than that equivalent to 1/30 of the LD50 . The number of the aberrant metaphases increased with increasing of the antibiotic dose . The maximum number of the cells with impaired chromosomal apparatus was observed 6 hours after the antibiotic administration . In 72 hours it decreased to the level of spontaneous mutations in myelocariocytes . Cytogenetic activity of 4'-epidoxorubicin was comparable to that of doxorubicin (adriablastin) widely used in medical practice. Antibiot Khimioter, 1989 Mar, 34(3), 213 - 5 {Screening of antineoplastic antibiotics using a rapid method of evaluating their cytostatic effect on tumor cells}; Volkolupova OP et al.; The study was aimed at development of a rapid method for estimating in vitro cytostatic action of antitumor antibiotics on the basis of intensity of inclusion of labeled precursors into nucleic acids of tumor cells which should be useful in primary screening of antibiotics with potential antitumor activity . The method was applied to substances isolated from 600 cultures of actinomycetes . 35 antibiotics showed antitumor activity; 8 of them were studied in detail . They proved to be novel antibiotics having antitumor activity in animals. Jpn J Antibiot, 1989 Mar, 42(3), 567 - 72 {Determination of particulate matter in small volume antibiotic injections}; Niizeki M et al.; Amounts of particulate matter present in 17 small volume antibiotic injections marketed in Japan were determined using light obscuration particle analyzer (HIAC) . The vial volume range of each batch of product was 7-20 ml, and each vial contained 1 g as antibiotic potency . In 4 products, contents of particles between 2.5 and 10 microns in diameter were counted 2,000-7,000 per vial, and particles in other products were counted less than 2,000 per vial . Numbers of particles greater than or equal to 10 microns in diameter were much less than the USP XXI criteria for particulate matter in small volume injections . The product of the highest counts for particles between 10 and 25 microns in diameter showed counts amounted to 0.13% of the USP XXI criteria . In the 25-50 microns particulate diameter range, particulate matters were detected only in 2 products, and they were less than 0.2% of the USP XXI criteria . Particles over 50 microns in diameter were not detected in any products . These results showed that 17 small volume antibiotic injections marketed in Japan had good qualities regarding contents of particulate matter. Izv Akad Nauk SSSR Biol, 1989 Mar-Apr, (2), 184 - 90 {Effect of anthracycline antibiotics on the cellular proliferation of human breast cancer heterografts growing in diffusion chambers in vivo}; Batomunkueva TV et al.; A comparative study of an effect of four anthracycline antibiotics on cell proliferation has been studied . All the four drugs exert significant inhibitory influence on cell proliferation . The data obtained do not explain different sensitivity of breast cancer tissues to these antibiotics in clinical practice. Z Naturforsch {C}, 1989 Mar-Apr, 44(3-4), 212 - 6 Molecular orbital analysis and quantitative structure-activity relationships for the anthracycline antibiotics; Bushelev SN et al.; Semiempirical CNDO/2 calculations of the electronic and molecular structures have been carried out for six antitumor anthracycline antibiotics . The strong correlation between their biological activity and such molecular properties as chromophore dipole moment, energy of frontier orbitals, and steric volumes was found and the proper QSAR equations were constructed . The molecular mechanics model showed the weak dependence the DNA-intercalation energy on differences in chromophore constituents (C4 and C9 positions) . The expression for the intercalation energy has also been obtained on the ground of a quantum-statistical approach; it was applied to the DNA-intercalation energy calculations for the same six anthracyclines . The results agree with the molecular mechanics ones quite satisfactory. Vestn Otorinolaringol, 1989 Mar-Apr, (2), 3 - 5 {Prevention of neurosensory hearing disorders in antibiotic-induced ototoxicosis}; Dunaivitser BI et al.; On the basis of clinical and audiological examinations of 102 tuberculosis patients who were on a combined treatment which included aminoglycoside antibiotics (streptomycin and canamycin), neurosensory disorders of the hearing function were detected in 75% of them . A clinical trial of obsidan, a beta-blocking agent, was performed in which it was used as a protective drug against ototoxic antibiotics given to 112 patients . Its combined application with antibiotics of the aminoglycoside series decreased their toxic effect from 75.6% to 21.4%. Fam Pract, 1989 Mar, 6(1), 27 - 32 Effects of a health activist course on knowledge and awareness of antibiotic use; Hermoni D et al.; A cohort study investigated the specific outcomes of a health education coursed carried out by recently graduated physicians in an urban primary care setting in Israel . Questionnaires were used to study the effects of the programme on knowledge and awareness concerning antibiotic usage . The results showed a significant gain in knowledge about the causes of infectious disease, appropriate duration of antibiotic intake, side effects of antibiotics and the importance of compliance . In contrast with other studies, low income blue collar workers with less than high school education showed the most significant gains from the programme . Inexperienced physicians were able to implement a community health education programme with clearly defined goals. J Antibiot (Tokyo), 1989 Mar, 42(3), 374 - 81 Synthetic studies of 1-beta-methylcarbapenem antibiotics; Shibata T et al.; The diastereoselective synthesis of the 1-beta-methylcarbapenems, (1R,5R,6S)-6-((R)-1-hydroxyethyl)-2-((S)-1-acetimidoylpyrrolidin-3 - ylthio)-1- methyl-1-carbapen-2-em-3-carboxylic acid and sodium (1R,5R,6S)-6-((R)-1-hydroxyethyl)-2-(5-chloro-2-oxobenzoxazolin-3- y l)-1- methyl-1-carbapen-2-em-3-carboxylate has been achieved . The key step was an aldol reaction between the achiral boron enolate which was generated from dibutylboron triflate and 3-propionyl-2-oxobenzoxazoline, and (3R,4R)-4-acetoxy-3-((R)-1-hydroxyethyl)azetizin-2-one. Biomaterials, 1989 Mar, 10(2), 136 - 8 Antibiotic-metal interactions in saline medium; von Fraunhofer JA et al.; The commonly used surgical alloys, stainless steel, titanium and Vitallium, were exposed to normal saline solution containing antibiotics frequently used for the control and treatment of orthopaedic infections and the corrosion potential versus time behaviour was followed . It was found that only one antibiotic, oxytetracycline, exerted a significant effect on electrochemical behaviour, producing an anodic shift of 120-250 mV in the Ecorr of the three metals . The study indicated that oxytetracycline at addition levels of 0.01-1.0 mg/ml acts as an anodic corrosion inhibitor. J Dent Que, 1989 Mar, 26, 99 - 104 {Choice of antibiotics in periodontology}; Landry RG et al.; For periodontal treatment, the use and choice of antibiotics is a controversial matter . There are many medical reasons for prescribing antibiotics before, during and after periodontal treatment . The purpose of this paper is to review the indications and reasons for antibiotherapy in periodontics . Research is not very advanced in this domain and there is a need to understand the indications for antibiotherapy in periodontics. Zhongguo Yao Li Xue Bao, 1989 Mar, 10(2), 177 - 80 {Affinity of penicillin-binding proteins of Escherichia coli K-12 for furbenicillin and other beta-lactam antibiotics}; Lei Y et al.; Penicillin-binding proteins (PBP) are vitally important targets in relation to the killing of bacteria by beta-lactams . The affinities of PBP of Escherichia coli K 12 for ampicillin, mecillinam and for ureidopenicillins were studied by sodium dodecylsulphate polyacrylamide slab gel electrophoresis and fluorography . The results showed that furbenicillin, a semisynthetic ureidopenicillin developed in China, bound to all 3 essential target proteins of E coli . The IC50 values of furbenicillin to PBP 1 b, PBP 2 and PBP 3 were 4.55 mg/L, 0.37 mg/L and 0.06 mg/L, respectively . The affinities of the 3 proteins of E coli for furbenicillin were 2.5-, 3.5-, and 2.5-fold, respectively higher than that of azlocillin . Mecillinam bound exclusively to PBP 2 (IC50: 0.16 mg/L) . Mezlocillin and piperacillin showed higher affinities for PBP 3 than furbenicillin, but their affinities for PBP 1 b and PBP 2 were much lower than furbenicillin. Mikrobiologiia, 1989 Mar-Apr, 58(2), 199 - 201 {The effect of oxygen deficiency on the stability of the yeast Saccharomyces cerevisiae to the polyenic antibiotic nystatin}; Ekhvalova TV et al.; Oxygen deficiency was shown to affect the resistance of different Saccharomyces cerevisiae strains to nystatin, a polyenic antibiotic . This resistance decreased upon oxygen deficiency in the wild-type strains alpha'1 and 7A-P192 as well as in the mutant strains NYS 2, NYS 3 and NYS 4, but remained unchanged in the mutants NYS-1 and NYS 5 . The qualitative composition of sterols was studied in the strains with a modified ergosterol synthesis, which were grown under the conditions of oxygen deficiency . Such conditions exerted a considerable effect on the accumulation of intermediate products in ergosterol biosynthesis. Mikrobiol Zh, 1989 Mar-Apr, 51(2), 22 - 5 {Biosynthesis of oleandomycin by cultures of Streptomyces antibioticus obtained after regeneration and fusion of protoplasts}; Shevchenko AA et al.; The ability of Streptomyces antibioticus strains to synthesize oleandomycin is studied under the effect of regeneration and fusion of protoplasts . The production of strains-regenerants with an increased (by 30-50%) synthesis of oleandomycin is possible . Regenerants of mutants resistant to the proper antibiotic retain a high level of the oleandomycin synthesis more stably . Variations in the antibiotic-production ability are considered in regenerant populations of various generations. Toxicol Lett, 1989 Mar, 46(1-3), 107 - 23 Nephrotoxicity of aminoglycoside antibiotics; Tulkens PM; Aminoglycoside antibiotics cause transient, usually nonoliguric, renal failure in up to 10-30% of patients treated with these drugs, and are the cause of the largest proportion of drug-induced acute nephrotoxicities . The toxic mechanism includes (i) uptake of the drug by proximal tubular cells, where it is first sequestered within lysosomes and (ii) development of a lysosomal phospholipidosis, which is rapidly associated with cell necrosis and various alterations to subcellular structure and function . Tubular necrosis is often accompanied by (and probably triggers) tubular regeneration and peritubular proliferation . The means whereby such tubular alterations eventually cause a decline in glomerular filtration and hypo-osmotic polyuria has not been established . Various in-vitro and acellular models have been designed to assess and screen for the nephrotoxic potential of aminoglycosides; of these, methods based on the analysis of aminoglycoside-phospholipid interactions appear to be the most meaningful . A number of patient- and drug-related risk factors have been identified, and their avoidance could significantly reduce the risk of nephrotoxic reactions . Because the uptake of aminoglycosides by the kidney is saturable, administration of daily doses of these drugs as one or two injections, rather than as multiple injections or by continuous infusion, may also decrease the risk for toxicity. Postgrad Med, 1989 Mar, 85(4), 333 - 4, 337-9 Treatment of pancreatitis . When do antibiotics have a role? Byrne JJ, Treadwell TL. Experimental and clinical data on the use of antibiotics in treatment of pancreatitis vary widely, depending on the cause of the disease . Antibiotics have little effect on alcoholic or idiopathic pancreatitis, but they play a major role in treatment of bacterial infections in gallstone pancreatitis . Some antibiotics are effective in necrotizing pancreatitis; however, surgery and extensive debridement are often necessary when abscess is present or multiple-organ failure occurs. Hepatology, 1989 Mar, 9(3), 423 - 6 Polymorphonuclear cell count response and duration of antibiotic therapy in spontaneous bacterial peritonitis; Fong TL et al.; The purposes of this study were (a) to measure serially ascitic fluid polymorphonuclear cell response in treated spontaneous bacterial peritonitis and (b) to determine whether an ascitic fluid polymorphonuclear cell count of less than 250 per mm3 on serial paracenteses was a satisfactory endpoint for antibiotic therapy . Thirty of 33 patients showed an exponential fall in ascitic fluid polymorphonuclear cell count after 48 hr of antibiotic therapy; the magnitude of decrease correlated with survival (p less than 0.01) . Among the patients whose antibiotic therapy was discontinued when the ascitic fluid polymorphonuclear cell count reached 250 per mm3 or less, the duration of therapy was considerably shorter than for the patients who received "conventional" therapy (p less than 0.01) . Recurrence of spontaneous bacterial peritonitis was similar in the two groups . Mortality correlated with the severity of underlying liver disease but not with duration of antibiotic therapy. Obstet Gynecol, 1989 Mar, 73(3 Pt 1), 326 - 9 Efficacy of oral antibiotics following parenteral antibiotics for serious infections in obstetrics and gynecology; Hager WD et al.; Patients with serious soft-tissue infections in obstetrics and gynecology are frequently treated with parenteral antibiotics until afebrile and clinically well for 48-72 hours, and then discharged on a broad-spectrum oral antibiotic . To evaluate the efficacy of this type of management, we designed a prospective, randomized single-blinded study comparing a group of patients who received oral antibiotics after hospital discharge (N = 80) with a group who did not (N = 83) . No significant differences in age, race, parity, diagnosis, or pathogen isolated were observed between the patients in the two groups . No significant difference was noted in delayed morbidity between those who did and those who did not take oral antibiotics (P greater than .06) . In light of the cost of oral antibiotics and the chance of drug-induced side effects, the data suggest that oral antibiotics after parenteral antibiotics are not indicated. J Gen Microbiol, 1989 Mar, 135 ( Pt 3), 583 - 91 Arsenical resistance of growth and phosphate control of antibiotic biosynthesis in Streptomyces; Hanel F et al.; Twenty-six wild-type Streptomyces strains tested for resistance to arsenate, arsenite and antimony(III) could be divided into four groups: those resistant only to arsenite (3) or to arsenate (2) and those resistant (8) or sensitive (13) to both heavy metals . All strains were sensitive to antimony . The structural genes for the ars operon of Escherichia coli were subcloned into various Streptomyces plasmid vectors . The expression of the whole ars operon in streptomycetes may be strain-specific and occurred only from low-copy-number plasmids . The arsC gene product could be expressed from high-copy plasmids and conferred arsenate resistance to both E . coli and Streptomyces species . The ars operon expressed in S . lividans and the arsC gene expressed in S . noursei did not render the synthesis of undecylprodigiosin and nourseothricin, respectively, phosphate-resistant . In addition in wild-type strains of Streptomyces phosphate sensitivity of antibiotic biosynthesis did not show strong correlation with resistance of growth to arsenicals. J Pharm Pharmacol, 1989 Mar, 41(3), 145 - 8 Solid state adsorption of antibiotics onto sorbitol; Nikolakakis I et al.; The ability of two types of sorbitol, instant and crystalline, to hold antibiotics permanently after mixing has been assessed by an air sieving technique . Sorbitol instant was found to have a greater adsorption capacity and binding strength than crystalline sorbitol . The six antibiotics studied were found to fall roughly into two groups of different adsorption capacities: (1) pivampicillin, cephalexin monohydrate and erythromycin ethylsuccinate, and (2) ampicillin trihydrate, amoxycillin trihydrate and cloxacillin sodium . The former have slightly higher levels of adsorption than the latter . A negative linear relationship was found between the amount of antibiotic adsorbed onto dry sorbitol and that originally added to sorbitol . When adsorption is expressed as the weight of drug adsorbed per unit weight of sorbitol, an 'apparent' Langmuir isotherm results . This suggests that there are a number of adsorption sites available for holding drug particles, these sites being different for the different antibiotics. Gastroenterol Clin North Am, 1989 Mar, 18(1), 51 - 6 Antibiotics and inflammatory bowel diseases; Gitnick G; In evaluating the medical literature dealing with antibiotics and inflammatory bowel diseases, I cannot help but recall the adage: "Those who have enthusiasm have no controls and those who have controls have no enthusiasm." There just are not enough data to justify the use of most antibiotics in the treatment of most patients with Crohn's disease or ulcerative colitis . An increasing body of data does support the use of metronidazole in selected patients with Crohn's disease, especially those with perianal disease or fistulae . However, this drug has important side effects that may preclude its long-term use . Other antibiotics have been inadequately tested and there is not adequate evidence to support their use. Antibiot Khimioter, 1989 Mar, 34(3), 218 - 23 {Value of determining the spectrum of blood serum fatty acids in evaluating increasing the effectiveness of antibiotic therapy of dysentery in children with prodigiozan and ephedrine}; Vereshchagin IA et al.; One hundred and ninety one children with acute Sonne and Flexner dysentery were observed with respect to the disease process, immunity indices and blood serum fatty acid spectrum . 104 children were treated with monomycin alone and 87 children were treated with the antibiotic in combination with prodigiozan and ephedrine as immunostimulators . It was shown that the recovery terms in the patients treated with the use of the immunostimulators decreased as compared to the patients treated with the antibiotic alone . The fatty acid spectrum in the children treated with the use of the immunostimulators differed from that in the children treated without them by low levels of fatty acids of the C12:0 to C18:1 composition. Vet Microbiol, 1989 Mar, 19(3), 253 - 62 Effect of antibiotics on clinical, pathologic and immunologic responses in murine Potomac horse fever: protective effects of doxycycline; Rikihisa Y et al.; Effects of three antibiotics on clinical, pathologic and immunologic responses in murine Potomac horse fever caused by Ehrlichia risticii infection were examined . When antibiotics were given after the development of clinical signs, antibiotics ranked in the order of reducing clinical signs and in preventing body weight loss and an intestinal enlargement were doxycycline, demeclocycline and rifampin . Infected mice treated with doxycycline and demeclocycline developed greater splenomegaly than rifampin-treated or untreated infected mice . All antibiotics used prevented thymic atrophy due to E . risticii infection . Indirect fluorescent antibody titers were highest with doxycycline treatment . Mice treated with demeclocycline and rifampin produced higher antibody titer than those without treatment . Ehrlichia risticii was reisolated from the spleens of both untreated and rifampin-treated infected mice . The effects of administering single doses of doxycycline at different times after infection were examined . Body weight loss was prevented by the drug given at every treatment day examined, i.e . Days 3, 5 and 7 post-infection (PI) . Thymic atrophy was minimum in mice treated at Day 5 PI, while splenomegaly was found on every treatment day . Splenocyte proliferative response to concanavalin A and lipopolysaccharide, and specific antibody development against E . risticii was best in mice treated at Day 5 PI followed by those treated at Day 3 and Day 7 PI. FEBS Lett, 1989 Feb 13, 244(1), 99 - 102 Interaction of the pore forming-peptide antibiotics Pep 5, nisin and subtilin with non-energized liposomes; Kordel M et al.; The cationic peptide antibiotics Pep 5, nisin and subtilin depolarize bacterial and artificial membranes by formation of voltage-dependent multi-state pores . Studies with non-energized liposomes indicated that the peptides do not span the membrane in the absence of a membrane potential . The effects of Pep 5 and nisin on neutral membranes, as studied by membrane fluidity, phase transition points and carboxyfluorescein efflux, were small compared to melittin . Acidic liposomes were affected more strongly, indicative of primarily electrostatic interactions with phospholipid head groups . Subtilin may slightly enter the hydrophobic core as suggested by tryptophan fluorescence quenching and liposome fusion experiments. J Antibiot (Tokyo), 1989 Feb, 42(2), 276 - 82 A new group of antibiotics, hydroxamic acid antimycotic antibiotics . II . The structure of neoenactins NL1 and NL2 and structure-activity relationship; Okada H et al.; The structures of neoenactins (NEs) NL1 and NL2, novel antimycotic antibiotics produced by Streptoverticillium olivoreticuli in a precursor-oriented fashion, were elucidated by 1H and 13C NMR and mass spectroscopic studies . The structures of both antibiotics are closely related to that of NE-A, the major component of NE congeners, being classified in the group of hydroxamic acid antimycotic antibiotics in which L-serine and a diketo amine form a hydroxamic acid structure . To study the role of the carbonyl groups in the biological activities of the hydroxamic acid antimycotic antibiotics, NE-A was modified by reaction with various carbonyl reagents . In terms of antimycotic activity, the derivatives are classified into two distinct groups; the first ones are fairly comparable to but not exceeding and the second ones are less active than NE-A depending on their tendency to revert to NE-A by hydrolysis . In general, the biological activities of the derivatives are inversely proportional to their stabilities to hydrolysis. J Antibiot (Tokyo), 1989 Feb, 42(2), 268 - 75 Ramoplanin (A-16686), a new glycolipodepsipeptide antibiotic . IV . Complete sequence determination by homonuclear 2D NMR spectroscopy; Kettenring JK et al.; Homonuclear 2D NMR spectroscopy double quantum filter correlation spectroscopy (DQF-COSY), relayed-COSY, nuclear Overhauser enhancement spectroscopy (NOESY), and DQF-relayed-NOESY) allowed the complete determination of the core depsipeptide of antibiotic ramoplanin (A-16686) . In particular, the DQF-relayed-NOESY experiments were essential in assigning the single signals close to the diagonal. J Antibiot (Tokyo), 1989 Feb, 42(2), 223 - 9 Myrocin C, a new diterpene antitumor antibiotic from Myrothecium verrucaria . II . Physico-chemical properties and structure determination; Hsu YH et al.; The structure of a new antitumor antibiotic, myrocin C, from a strain of Myrothecium verrucaria was characterized as a pentacyclic pimarane diterpene composed of a gamma-lactol group and a unique cyclopropane ring on the basis of its physico-chemical properties and spectroscopic data as well as a single-crystal X-ray diffraction analysis of its monoacetyl derivative. Ann Allergy, 1989 Feb, 62(2), 91 - 3 Three cases of fatal anaphylaxis to antibiotics in patients with prior histories of allergy to the drug; Hoffman DR et al.; Three cases of fatal anaphylaxis to penicillin and cephalexin are described . All three patients had prior histories of severe allergic reactions to the antibiotics they were given . The radioallergosorbent test was positive on post-mortem blood to the appropriate antibiotic in all three cases . RAST can be performed on post-mortem specimens of serum, sodium fluoride-treated blood, or whole blood. J Med Chem, 1989 Feb, 32(2), 402 - 8 Synthesis, cytotoxicity, and antiviral activity of some acyclic analogues of the pyrrolo{2,3-d}pyrimidine nucleoside antibiotics tubercidin, toyocamycin, and sangivamycin; Gupta PK et al.; A number of 7-{(1,3-dihydroxy-2-propoxy)methyl}pyrrolo{2,3d-d}pyrimidine derivatives that are structurally related to toyocamycin and sangivamycin and the seco nucleosides of tubercidin, toyocamycin, and sangivamycin were prepared and tested for their biological activity . Treatment of the sodium salt of 4-amino-6-bromo-5-cyanopyrrolo{2,3-d}-pyrimidine with 1,3-bis(benzyloxy)-2-propoxymethyl chloride afforded compound 3, which without isolation was debrominated to obtain 4-amino-5-cyano-7-{{1,3-bis(benzyloxy)-2- propoxy}methyl}pyrrolo{2,3-d}pyrimidine . Although catalytic hydrogenolysis failed, the benzyl ether functionalities of 4 were successfully cleaved by boron trichloride to afford 4-amino-5-cyano-7-{(1,3-dihydroxy-2- propoxy)methyl}pyrrolo{2,3-d}pyrimidine . Conventional functional group transformation of the cyano group of 6 provided a number of novel 5-substituted derivatives . Tubercidin (8a), toyocamycin (8b), and sangivamycin (8c) were treated separately with sodium metaperiodate and then with sodium borohydride to afford the 2',3'-seco derivatives 9a-c, respectively . The acyclic nucleoside 4-chloro-2-(methylthio)-7-{{1,3-bis(benzyloxy)-2- propoxy}methyl}pyrrolo{2,3-d}pyrimidine was aminated, desulfurized with Raney Ni, and then debenzylated to provide the tubercidin analogue 11 . Cytotoxicity evaluation against L1210 murine leukemic cells in vitro showed that although the parent compounds tubercidin (8a), toyocamycin (8b), and sangivamycin (8c) were very potent growth inhibitors, the acyclic derivatives 6, 7a-c, and 9a-c had only slight growth-inhibitory activity . Evaluation of compounds 6, 7a, 7b, 7c, 9a, 9b, 9c, 11 for cytoxicity and activity against human cytomegalovirus (HCMV) and herpes simplex virus type 1 (HSV-1) revealed that only the carboxamide (7a) and the thioamide (7c) were active . Compound 7c was the more potent of the two, inhibiting HCMV but not HSV-1 at concentrations producing little cytotoxicity. Antibiot Khimioter, 1989 Feb, 34(2), 109 - 12 {A rapid immunofluorescent method of determining the antibiotic sensitivity of brucella}; Gubina EA et al.; Optimal conditions for rapid assay of Brucella antibiotic sensitivity with the immunofluorescent method were developed . With this method high sensitivity of the main Brucella species to tetracycline, doxycycline and rifampicin was confirmed . It was found actually possible to use the immunofluorescent method for rapid assay of Brucella antibiotic sensitivity in practice. Hindustan Antibiot Bull, 1989 Feb-May, 31(1-2), 38 - 9 Effect of some antibiotics on Macrophomina phaseolina, a charcoal rot fungus of soybean; Dubey RC; Effect of agrimycin-100, ampicillin, griseofulvin and tetracycline on colony growth of Macrophomina phaseolina, incitant of charcoal rot of soybean has been studied in vitro . Amongst them tetracycline posed most effective inhibiting the growth by 73.9% at 1000 micrograms/ml concentration . On the basis of effectiveness antibiotics have been listed as tetracycline greater than ampicillin greater than griseofulvin greater than agrimycin-100. J Antibiot (Tokyo), 1989 Feb, 42(2), 254 - 67 Ramoplanin (A-16686), a new glycolipodepsipeptide antibiotic . III . Structure elucidation; Ciabatti R et al.; By combination of chemical, 1H and 13C NMR, and mass spectrometric studies, the structures of the three components of the antibiotic ramoplanin (A-16686), produced by Actinoplanes sp . ATCC 33076, have been elucidated . All the components have structures formed by a common depsipeptide skeleton carrying a dimannosyl group and are differentiated by the presence of various acylamide moieties, derived from C8, C9 and C10 fatty acids. Bioorg Khim, 1989 Feb, 15(2), 277 - 80 {"Chimeric" antibiotics, daunorubicin and its analogs N-acylated with bruneomycin (Streptonigrin)}; Tolstikov VV et al.; Anthracycline antibiotics (daunorubicin, carminomycin and doxorubicin) N-acylated with antibiotic bruneomycin (streptonigrin) have been obtained from the parent compounds upon treatment with N, N'-dicyclohexylcarbodiimide and N-hydroxysuccinimide . These "chimeric" antibiotics are less active both in vitro and in vivo than the parent antibiotics . This demonstrates the stability of the intermolecular amide linkage in these compounds towards chemical and enzymatic hydrolysis as well as their inability to interact with corresponding receptors in contrast to less hindered derivatives of the parent antibiotics. Eur J Pediatr, 1989 Feb, 148(5), 401 - 2 Treatment of fever and neutropenia with antibiotics versus antibiotics plus intravenous gammaglobulin in childhood leukemia; Sumer T et al.; Thirty-three children with leukemia who had neutropenia and fever were randomized to receive cefataxim and amikacin, versus the same antibiotics plus intravenous gammaglobulin (i.v . IgG) . Duration of neutropenia, hospitalization and the interruption of chemotherapy were not different in the two groups; however, duration of fever was significantly shorter in the i.v . IgG group. Hear Res, 1989 Feb, 37(3), 203 - 17 Blockage of the transduction channels of hair cells in the bullfrog's sacculus by aminoglycoside antibiotics; Kroese AB et al.; The action of aminoglycoside antibiotics on transduction by hair cells was investigated in isolated preparations of the bullfrog's sacculus . Bath application of aminoglycosides produced a reversible blockage of extracellularly recorded responses to displacements of the otolithic membrane . The half-blocking concentrations for various drugs were in the range 2-95 microM . The effect of dihydrostreptomycin on the receptor currents of individual hair cells was studied under two-electrode, voltage-clamp conditions . Iontophoretic application of drug to the apical cellular surface caused a reduction of the receptor current within 20 ms; the reduction was reversible within 1 s . The effect was most striking at holding potentials more negative than -60 mV and was relieved by depolarization . The effect of intracellular aminoglycosides was investigated in cells voltage-clamped with the tight-seal, whole-cell technique . Gentamicin and dihydrostreptomycin, at concentrations near 100 microM, did not block transduction under these conditions . The acute, reversible blocking effect of aminoglycosides therefore occurs from the extracellular membrane surface . The results are consistent with aminoglycosides' plugging the poorly ion-selective transduction channels of hair cells. Brain Res, 1989 Jan 30, 478(2), 403 - 6 Depression of calcium current at mouse motor nerve endings by polycationic antibiotics; Bourret C et al.; The hypothesis according to which polycationic antibiotics produce neuromuscular block by interfering with the Ca current of motor nerve terminals has been examined using external electrodes in nerve-muscle preparations of the mouse . It was found that kanamycin, bekanamycin and polymyxin B depressed presynaptic Ca currents probably by neutralizing negative surface charges. Schweiz Med Wochenschr, 1989 Jan 14, 119(2), 39 - 45 {Positive direct Coombs' test in acute leukemias and other hemoblastoses: relation to clavulanic acid-containing antibiotics?}; Blanchard M et al.; Alerted by a high incidence of positive autologous controls in pretransfusion compatibility testing for patients with acute leukemia, we retrospectively analysed 59 cases of severe hemoblastoses undergoing myelosuppressive treatment . Seventeen (29%) of these patients had a positive direct antiglobulin test (DAT) with the following characteristics: the test was of the IgG and/or C3d type in all but two cases, which reacted with polyvalent antiglobulin sera only; the reaction was very weak throughout; very high concentrations of monospecific sera were needed to elicit positive reactions; free antibodies were never detected in the patients' serum; the eluates of the patients' red cells were non-reactive against a very large panel of test erythrocytes . All these criteria suggested a non-immunologic absorption of proteins under the influence of drugs such as cephalosporins and clavulanic acid . Timenten (ticarcillin and clavulanic acid) was found to be the only common drug which had been administered to the majority of the patients with a positive DAT: 15 of the 17 patients with a positive DAT (88%) had received Timenten against 19 of 42 patients (45%) with negative DAT . 44% of all the patients receiving Timenten thus had a positive DAT, whereas only 8% of the patients without this drug reacted in this way . These data document the role of clavulanic acid in the development of a positive DAT . The literature and our experience show that this kind of unspecific binding of proteins to the red cell membrane is not associated with increased hemolysis . Knowledge of the phenomenon, however, is important for differential diagnosis of anemias and interpretation of difficulties arising during pretransfusional compatibility testing. J Chromatogr, 1989 Jan 13, 462, 315 - 22 Improvement of chemical analysis of antibiotics . XV . Isocratic high-performance liquid chromatographic methods for the analysis and preparative separation of the components of bacitracin; Oka H et al.; Isocratic high-performance liquid chromatographic (HPLC) systems were established for analytical and preparative separation of the components of the antibiotic preparation bacitracin (BC) . The best analytical results were obtained using a C18 modified silica gel column (Capcell Pak C18) with a solvent system of 0.04 M disodium hydrogenphosphate buffer and methanol (4:6), pH 9-10 . The calibration graphs showed good linear relationships between 50 and 1000 ng for BC-A and between 65 and 1000 ng for BC-F . With respect to the preparative HPLC, a Capcell Pak C18 column with methanol-0.05 M aqueous sodium sulphate solution (6:4) as a mobile phase gave satisfactory results . The isolation of BC-A and -F was readily achieved without decomposition of the components by using the present preparative HPLC followed by desalting on a prepacked C18 cartridge. Schweiz Med Wochenschr, 1989 Jan 7, 119(1), 19 - 21 {Antibiotic therapy and long-term course in spondylodiscitis}; Borner M et al.; Long-term outcome and therapy are reported in 29 patients with vertebral osteomyelitis . Antibiotics were administered for a mean period of 21 (6-102) weeks . In 13 patients surgery was additionally necessary . After a mean follow-up of 53 (10-136) months only one relapse had occurred . Radiographs and erythrocyte sedimentation rate were the best indicators of successful treatment. Vasa, 1989, 18(1), 30 - 4 {Prevention of infection in teflon prostheses for dialysis access . Experiences with a resorbable combined collagen-antibiotic system}; Horch R et al.; 40 patients with renal insufficiency and chronic hemodialysis received a E-PTFE prosthesis as vascular access either at the upper or lower extremity . The efficacy of prophylaxis of infection through application of a local aminoglycosid, administered as a resorbable collagen-antibiotic-sponge, was studied in two different groups . All patients had a high risk of infection . The use of the collagen-gentamycin-sponge was effective in preventing an infection of the vascular graft . Systemic side effects were not registrated in spite of the reduced renal function . Further studies are necessary to evaluate the efficacy of the collagen-gentamycin-sponge in preventing vascular prosthesis infection in high risk patients. J Antibiot (Tokyo), 1989 Jan, 42(1), 7 - 13 Viriplanin A, a new anthracycline antibiotic of the nogalamycin group . II . The structure of a novel hydroxyamino sugar from reduced viriplanin A; Kind R et al.; Methyl 2,3,6-trideoxy-3-hydroxyamino-3-C-methyl-alpha-D-ribo-hexopyranoside+ ++ (2) and the corresponding amino sugar (4) were isolated from reduced viriplanin A by acidic methanolysis and esterified to the di-p-bromobenzoates (3 and 5), respectively . The absolute configuration of crystalline 3 was determined by X-ray analysis to be alpha-D . This result could be confirmed by oxidation of 2 to methyl alpha-D-decilonitroside (6) and from the CD spectra of 3 and 5 . Thus, the nitrogen-containing sugars of viriplanin A and probably those of decilorubicin and arugomycin belong to the D-series. J Antibiot (Tokyo), 1989 Jan, 42(1), 18 - 29 Two new carbapenem antibiotic-producing actinomycetes: Kitasatosporia papulosa sp . nov . and Kitasatosporia grisea sp . nov; Nakamura Y et al.; Two new carbapenem antibiotic-producing actinomycetes, the cell-walls of which contain LL-diaminopimelic acid and meso-diaminopimelic acid, were isolated from soil . The two strains were subjected to taxonomic studies, which involved morphological, cultural, physiological and chemotaxonomical characterization, the latter including the cell-wall chemo-type, whole-cell sugar composition, phospholipid composition, menaquinone system and DNA base composition . These strains were identified as new species of the genus Kitasatosporia . The proposed names are Kitasatosporia papulosa for strain AB-110 (IAM 13637, FERM 9000, JCM 7250) and Kitasatosporia grisea for strain AA-107 (IAM 13638, JCM 7249). J Antibiot (Tokyo), 1989 Jan, 42(1), 1 - 6 Isolation and characterization of new antibiotics resorcinomycins A and B; Kondo E et al.; New antibiotics, resorcinomycins A and B, were isolated from the culture broth of a streptomycete strain identified as Streptoverticillium roseoverticillatum . The antibiotics are water-soluble amphoteric substances, positive to SAKAGUCHI'S reagent . The molecular formulas C14H20N4O5 and C13H18N4O5 for A and B were indicated by elemental analysis and secondary ion MS . The structures of these antibiotics were determined by 1H and 13C NMR spectrometry and some chemical evidences to be N-{(S)-alpha-guanidino-3,5-dihydroxy-4-isopropylphenylacetyl}glyci ne and N-{(S)-alpha-guanidino-3,5-dihydroxy-4-ethylphenylacetyl}-glycine, respectively. Acta Neurochir (Wien), 1989, 100(1-2), 79 - 83 Treatment of experimental brain abscess . 2 . Effects of combinations of hyaluronidase with antibiotics and dexamethasone; Pasaoglu A et al.; Brain abscess formation was studied experimentally in rats to determine the most appropriate nonsurgical treatment method by applying different combinations of hyaluronidase, dexamethasone and antibiotic sensitive to the inoculated bacteria in various stages of classical abscess development . The results showed that combined therapy with antibiotic and hyaluronidase started the day before inoculation averted the formation of brain abscess and the same therapy started after encapsulation, effectively eliminated the organisms and resolved the infection leaving a glial scar . But the same therapy, only started at the cerebritis stages, caused an increase of cerebritis . The addition of dexamethasone reduced the oedema but enhanced the cerebritis and delayed encapsulation . Though neurosurgical intervention continues to be the definitive method for eradicating the infection and preventing the pressure-related complications of brain abscess, our concept of management with hyaluronidase and appropriate antibiotic might be a new effective chemotherapeutic method of encapsulated brain abscesses in selected high-risk patients. Haemostasis, 1989, 19(4), 224 - 8 Effect of antibiotics on laser-induced thrombus formation in rat mesenteric arterioles; Weichert W et al.; Antibiotics were tested in a thrombosis model, in which thrombi are produced in small rat mesenteric arterioles . An interference contrast system based on a Leitz Orthoplan microscope, was used to visualize thrombus formation . Vascular lesions were produced with a Coherent CR-2 supergraphite ion laser (argon laser) in arterioles of 25-35 microns diameter . Cefmenoxim, cefotaxim (i.v.) and cephalexin orally at doses of 20 and 40 mg/kg and gentamycin 10 and 20 mg/kg (i.v.) had a marked and significant antithrombotic effect . Even more effective were cefoperazon and lamoxactam 20 and 40 mg/kg (i.v.) and tobramycin 10 and 20 mg/kg (i.v.) . Azlocillin, cefoxitin, mezlocillin or spectinomycin (20 mg/kg i.v.) and penicillin or piperacillin (50 mg/kg i.v.) also showed a significant antithrombotic effect, which, however, disappeared on doubling of the applied dose. Free Radic Res Commun, 1989, 7(1), 19 - 26 Minimum essential structural requirements for lactam antibiotic action; Kovacic P et al.; A mechanism of action encompassing mono- and bicyclic beta-lactams has been proposed previously, which stresses the importance of formation of an electron transfer (ET) entity (conjugated iminium) as a requirement for antibiotic activity, in association with enzyme inactivation . Additional evidence in support of this contention is now provided . Reduction potentials for several cephalosporins and pyrazolidinones, all of which contain an oximino functionality in the side chain, were observed in the range of -0.6 to -0.7 V . Comparison is made with related compounds lacking imine . Agents containing side chain hydrazone, oxamazins (mono beta-lactams), and lactivicin are discussed based on the ET approach. Acta Orthop Belg, 1989, 55(1), 1 - 11 {Treatment of chronic osteomyelitis in Africa with plaster implants impregnated with antibiotics}; Bouillet R et al.; Nineteen African patients with osteomyelitis were treated by curettage of the lesions and packing of the bone cavities with plaster of Paris pellets containing antibiotics (Fucidin and Amoxycillin) . Of 18 patients followed, 16 showed wound healing in an average of 3 to 6 weeks . Eight patients had regular roentgenographic examinations during a minimum of two months . In six of these patients, healing of the lesions and a significant osteogenic reaction were observed . The plaster pellets were resorbed in 3 to 6 weeks in all patients, and no signs of rejection were noted . In spite of insufficient follow-up due to medical conditions in Africa (Zaire), the study confirms the advantages of this simple treatment of osteomyelitis in underdeveloped countries. Drugs Exp Clin Res, 1989, 15(5), 211 - 8 Influence of antibiotics on motility and adherence of human neutrophils studied in vitro; Van der Auwera P et al.; The influence of 14 antibiotics on chemotaxis, motility and adherence of human neutrophils has been studied . Neutrophils were preincubated for 30 min at 37 degrees C with the antibiotics . Chemotaxis was studied in antibiotic-free and antibiotic-containing agar using zymosan-activated serum and fMLP as stimuli . Adherence was studied in plastic microtitre plates . Most of the antibiotics studied did not affect the three functions studied . Daptomycin occasionally decreased random migration without affecting chemotaxis and adherence . Chemotaxis was occasionally modified by some of the quinolones, although this depended on the volunteer tested . The level of inhibition could be significant in diseased patients. J Antibiot (Tokyo), 1989 Jan, 42(1), 73 - 83 Highly targeted screening system for carbapenem antibiotics; Nakamura Y et al.; An improved screening system in a search for carbapenem antibiotics from actinomycetes was developed, involving (1) effective isolation of carbapenem antibiotic producers, (2) favorable cultivation as to antibiotic production and (3) simplified identification of the carbapenem antibiotics: (1) A frequency of isolation of carbapenem antibiotic producers from soils was increased by the use of an amoxicillin/clavulanate-containing medium . As many as 20% of the actinomycetes isolated in this medium were found to be carbapenem antibiotic producers, as compared with 0.6% when conventional media were employed . (2) An agar-surface cultivation on oatmeal - yeast extract - malt extract (OMYM) medium, containing oatmeal, yeast extract, malt extract, glucose and trace elements, was most suitable for the antibiotic production . (3) An agar-diffusion assay for identification of carbapenem antibiotics was developed . Although the carbapenem antibiotics are stable against beta-lactamases, they were hydrolyzed completely with excess amounts of common beta-lactamases . So they could be discriminated from other beta-lactam antibiotics and non-beta-lactam antibiotics by comparison of the susceptibility profiles for such enzymes. Adv Exp Med Biol, 1989, 252, 313 - 8 Mechanism of the mitochondrial respiratory toxicity of cephalosporin antibiotics; Tune BM; In summary, cephaloglycin, a nephrotoxic cephalosporin, produces a specific pattern of mitochondrial toxicity, decreasing both respiration with and the net uptake of succinate in renal cortical mitochondria after either in vivo or in vitro exposure, with no effect on succinate efflux . There is little or no reduction of ADP uptake by the same toxic exposures . Cephalexin, which is not toxic in vivo, inhibits respiration and uptake only with in vitro exposure . Fragmentation of mitochondria, which allows access of succinate to intramitochondrial enzymes without the need for carrier-mediated uptake, partially corrects the respiratory toxicity of cephaloglycin . We conclude that cephalosporin toxicity to succinate transport parallels the pattern of injury to mitochondrial respiration and may be pathogenic in this respiratory toxicity . These observations are consistent with the hypothesis that a) both nephrotoxic and nontoxic cephalosporins can fit the carriers for mitochondrial anionic substrate transport, and b) in situ nephrotoxicity develops as inhibition of transport becomes irreversible through acylation of these carriers. Chemotherapy, 1989, 35(3), 187 - 92 Spectrum of the antimalarial activity of a new macrolide antibiotic midecamycin in mice and monkeys; Puri SK et al.; The antimalarial activity of a new macrolide antibiotic, midecamycin, has been evaluated against a sensitive strain of Plasmodium berghei, a chloroquine-resistant strain of P . yoelii nigeriensis and a simian parasite, P . cynomolgi B . The ED50 and ED90 values of this antibiotic administered in two divided daily doses were found to be 37.15 +/- 3.51 and 100.84 +/- 7.54 mg/kg, respectively, against P . berghei and 362.34 +/- 85.33 and 878.04 +/- 10.02 mg/kg, respectively, against P . yoelii nigeriensis . Doses above 45 mg/kg for 4 days significantly extended the mean survival time of treated mice infected with either of the two parasites . However, no appreciable blood schizontocidal (at 100 mg/kg X 7 days), anti-relapse (at 100 mg/kg X 7 days) or causal prophylactic activities (at 200 mg/kg X 3 days) were observed against P . cynomolgi infection in rhesus monkeys. Nauchnye Doki Vyss Shkoly Biol Nauki, 1989, (4), 84 - 8 {Effect of metal cations on the formation of antibiotic and pigment by the mycophilic fungus Hypomyces rosellus 94/77}; Toropova EG et al.; Using the method of mathematical planning of experiment the effect of calcium, magnesium, manganese, iron, zinc and copper on synthesis of antibiotic and pigment by mycophilic fungus Hypomyces rosellus has been studied . The ions of Mg2+, Mn2+, Fe2+ have been found to be important for antibiotic and pigment formation by fungus, the ions of Mg2+ and Mn2+ are interchangeable. Klin Khir, 1989, (1), 10 - 3 {Possibilities of increasing the effectiveness of antibiotics in surgical practice}; Shevchuk MG et al.; In 78 patients with acute appendicitis, penicillin with kanamycin in combination with methyluracil and levamisole were used . It was established that antibiotics in combination with immunostimulators restored the indices of immune reactivity of an organism, which were impaired in isolated use of antibiotics . In the experiment on 300 albino rats, the results confirming the clinical observations were obtained. Nippon Shokakibyo Gakkai Zasshi, 1989 Jan, 86(1), 50 - 9 {An experimental study on the biliary excretion of ceftizoxime in the presence and after relief of biliary obstruction with special reference to the influence of bile acid metabolism on the biliary excretion of the antibiotic}; Kawaguchi H; The biliary excretion of ceftizoxime (CZX) in the presence and after relief of biliary obstruction was experimentally investigated in twelve dogs . In the presence of biliary obstruction, the biliary excretion of CZX was impaired and, immediately after relief of biliary obstruction, the existence of reverse shunt from the vascular system to the biliary tract was suggested . After relief of biliary obstruction, the biliary excretion of CZX and the ratio of {lithocholic acid + deoxycholic acid}/{cholic acid + chenodeoxycholic acid} in the bile were impaired in one group with external drainage as compared to the other group with internal drainage . It was experimentally proved that the biliary excretion of antibiotics seemingly related very closely to the bile acid metabolism and that it was increased by administration of the bile acid after external drainage or by normalization of the enterohepatic circulation of the bile acid after internal drainage.
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