Int Endod J, 1989 Jan, 22(1), 9 - 16 The antibacterial properties of four elements released from dental restorative materials; Nourollahi M et al.; The antibacterial activity of four elements (zinc, copper, fluoride and mercury), previously reported to be released from dental restorative materials, was investigated . This was carried out using two aerobic micro-organisms isolated from dentine beneath cavities in the ferret . These were grown in the presence of the test elements over a concentration range of 10-100 micrograms/ml for 72 hours . Concentration and exposure time were found to have a highly significant effect on the growth and viability of both micro-organism . Zinc, mercury and copper exerted the greatest effect, fluoride the least. Probl Tuberk, 1989, (10), 26 - 9 {Acute pneumonia in persons with residual tuberculous lesions}; Butenko GE et al.; To elucidate the role of pneumonia in pathogenesis of reactivation of residual tuberculous lesions, time courses of clinicoroentgenological and immunological indices for a period of 3 to 5 years before detection of active tuberculosis were studied . Nonspecific bronchopulmonary aggravations progressing by the type of acute, persisting or abscessing pneumonia have many features providing their consideration as nonspecific "masks" of the specific process progression . The features are: localization, clinical picture, disease process, time course increasing of the host specific sensitization, hyperergic character of reactions to intracutaneous tests with tuberculin and BCG vaccine, signs of specific endobronchitis, no effect of nonspecific treatment and favourable time course of the process under the effect of specific antibacterial therapy. Symp Soc Exp Biol, 1989, 43, 367 - 77 Marine invertebrate mucus--agglutinating and antibacterial activity, with emphasis on Metridium senile; Astley MR et al.; The agglutinating and antibacterial activities of mucus from marine invertebrates are described . Mucus from eleven species was tested for the presence of haemagglutinins using a range of vertebrate erythrocytes . Mucus from Metridium senile, Ophiocomina nigra and Branchiostoma lanceolatum yielded positive results and was investigated further . The haemagglutinin of M . senile was purified, characterized and shown to be mannose-specific . Mucus from this animal was subsequently assayed for antibacterial activity using seawater isolates and verified marine and terrestrial cultures . Only two test organisms were inhibited, while the majority showed significantly enhanced growth . Possible functions of the mucus barrier in marine invertebrates are discussed. Ter Arkh, 1989, 61(3), 84 - 7 {Pathogenesis of acute pneumonia}; Novozhenov VG et al.; The patients with acute pneumonias demonstrated interdependent changes in lipid peroxidation (LPO), antioxidant system (AOS), immune system (IS), and in the pituitary-adrenocortical system (PAS), related to the character of the disease course . The most pronounced changes were seen in the patients with acute pneumonias eventuating in pneumofibrosis . The high level of LPO was combined with AOS depletion, immunodeficiency formation, and with dysfunction of the PAS . Antibacterial treatment did not exert any appreciable effect on the characteristics under study . Thus, the level of LPO and AOS status are important components in the pathogenesis of acute pneumonias, determining the character of the disease course and outcome . It is advisable that research work aimed at the design of the principles of antioxidant therapy may be intensified. Acta Leprol, 1989, 7 Suppl 1, 195 - 9 Studies on the mechanisms of the synergistic effects of ethambutol and other antibacterial drugs on Mycobacterium avium complex; Hoffner SE et al.; Synergistic effects of combinations of anti-mycobacterial drugs on Mycobacterium avium complex (MAC) in vitro was studied by radiometric respirometry . Pronounced synergy was seen for several drug combinations where ethambutol was found to be the key drug in the synergistic potentiation . Microcalorimetric studies show that a very rapid physico-chemical interaction occurs between the cell-surface of MAC and ethambutol . When MAC cells were pretreated with ethambutol and then subjected to streptomycin the thermal response significantly differed from that seen with MAC cells which had not been pretreated . The typical thermal effects of the interaction of ethambutol with live and UV-killed MAC cells was not seen with heat-killed MAC cells . It is proposed that specific cell-surface protein(s) act as receptors in the initial interaction with ethambutol. Antimicrob Agents Chemother, 1989 Jan, 33(1), 58 - 62 Production of a streptomycin-Park nucleotide complex by Streptomyces griseus; Szabo I et al.; A compound (compound X) with antibacterial activity was isolated from early-exponential-phase cultures of the streptomycin producer Streptomyces griseus and from protoplast cultures of the same strain . The protoplast cultures produced a larger amount of compound X than did the young hyphae . Both the mycelia and the protoplasts incorporated 14C-labeled myo-inositol, a precursor of streptomycin, into compound X, which has an amino acid content related to that of the cell wall peptidoglycan of the producer strain . Compound X may contain a streptomycin molecule covalently bound to a cell wall precursor unit, i.e., to a Park nucleotide (J . T . Park, J . Biol . Chem . 194:897-904, 1952), through the glutamic acid of the pentapeptide component. Antimicrob Agents Chemother, 1989 Jan, 33(1), 113 - 4 In vitro activity of cefpodoxime proxetil (U-76,252; CS-807) against clinical isolates of Branhamella catarrhalis; Sarubbi FA et al.; Cefpodoxime proxetil (U-76,252; CS-807) is a new esterified oral cephem antibiotic with a broad antibacterial spectrum . Since data regarding the activity of cefpodoxime against Branhamella catarrhalis are limited, we tested its activity against 200 B . catarrhalis isolates . The drug was highly active against beta-lactamase-negative and -positive isolates; 99% of all strains tested showed a cefpodoxime proxetil MIC of less than or equal to 2.0 micrograms/ml. J Pharm Biomed Anal, 1989, 7(12), 1837 - 46 Residue determination of two co-administered antibacterial agents--cephalexin and colistin--in calf tissues using high-performance liquid chromatography and microbiological methods; Leroy P et al.; Residues of two antibacterial agents, cephalexin and colistin, co-administered by intramuscular injection to calves, were quantified in four different tissues (muscle, fat, liver and kidney) by column switching HPLC and by a microbiological method . For cephalexin assay, tissue samples with cephradin as internal standard were homogenized in a 5% trichloroacetic acid solution and filtrates were injected onto a concentration precolumn filled with LiChroprep RP-18 (25-40 microns) . A clean-up step was incorporated by flowing a mobile phase (methanol-0.01 M phosphate buffer (pH 3.0); 15:85, v/v) through the enrichment column before elution on a LiChrospher RP-18e (5 microns) column with a methanol-phosphate buffer (30:70, v/v) at a flow rate of 1 ml min-1 . Spectrometric detection was at 260 nm . An additional "off-line" washing step of extracts with methylene chloride was operated to achieve higher selectivity in the case of liver and kidney samples . The limit for quantitative assay was 0.045 micrograms g-1 with relative standard deviations in the range 5-8% and recoveries within 70% . For microbiological assay of colistin, samples were homogenized in 0.1 M hydrochloric acid-acetonitrile mixtures (3:1, v/v, for kidney and liver; 3:2, v/v, for fat and muscle) . The supernatants were assayed by the cylinder plate method after evaporation to dryness under vacuum . Bordetella bronchiseptica ATCC 4617 was chosen as test organism . After a 3-h diffusion step at room temperature, the medium was incubated at 37 degrees C for 18 h and then the diameter of the growth inhibition zones was measured . Sensitivity reached 0.10-0.15 micrograms g-1 . Results from the analysed samples over a 7-28 day period after drug administration show that no cephalexin was found at concentrations higher than the quantitation limit in the four test tissues and that colistin was found in muscle (injection site only) for 15 days and in kidney for 21 days. J Pharm Biomed Anal, 1989, 7(12), 1791 - 7 Bio-analysis and preliminary pharmacokinetics of the experimental antitumour drug LL-D49194 alpha 1; Underberg WJ et al.; LL-D49194 alpha 1 is a recently discovered compound, produced by Streptomyces vinaceus-drappus . This micro-organism produces a number of antibiotics, all showing antibacterial and antitumour activity, of which LL-D49194 alpha 1 is one of the main compounds . The compounds' antitumour effectiveness has been proven in vitro and the drug is undergoing further tests . For the assay of the drug in plasma a high-performance liquid chromatographic (HPLC) system has been developed, preceded by a clean-up step . The drug is extracted from the biological matrix with ethyl acetate followed by direct HPLC analysis of the organic layer via an analytical RP8 column preceded by a guard column to retain endogenous plasma compounds . Detection of drug and metabolites was carried out by fluorescence with reference to a non-fluorescent internal standard detected by UV absorption . The detection limit was 1 ng ml-1 plasma (using 1 ml sample; signal-to-noise ratio, 3), i.e . 1 ng on column . The method has been utilized in a preliminary pharmacokinetic study in rat. Acta Med Pol, 1989, 30(1-2), 45 - 50 Bacterial capacity of blood platelets in patients suffering from pneumonia; Kemona H et al.; The percent of bacteria engulfed by blood platelets, surviving in them and killed was determined in these cells taken from 22 patients with pneumonia before the treatment and from 14 patients after the treatment . The mean percent of bacteria phagocytosed by platelets collected before the treatment was 6.28 and by those after the treatment 5.01, being considerably higher than in the control group (3.42) . The mean percent of bacteria surviving in platelets taken before the treatment equalled 3.10 and after the treatment 2.36 being also higher than in the control group (1.32) . The mean percent of bacteria killed by platelets taken before the treatment was 3.18 and by those taken after the treatment 2.65, being also higher than in the control group . These results seem to indicate that in cases of pneumonia the blood platelets are involved into the antibacterial activity. Lens Eye Toxic Res, 1989, 6(1-2), 339 - 51 Intraocular dynamic mode differences of new quinolone antibacterial agents between pigmented and albino rabbit eyes; Fukuda M et al.; The influence of melanin on the intraocular dynamics of a new quinolone anti-bacterial agent, NY-198, was investigated in albino and pigmented rabbit eyes . Drug uptake into the cornea of the removed eye was almost the same in both albino and pigmented eyes . However, drug uptake into the iris-ciliary body and release volume and time from the tissues were significantly higher and longer in pigmented eyes than in albino rabbit eyes . Penetration of NY-198 into the cornea, the iris-ciliary body and the serum, administered either systemically or locally into the living eyes of pigmented rabbit was significantly higher than that observed in albino rabbit eyes . Drug affinity for melanin was examined utilizing synthetic melanin . Regarding OFLX, NY-198, CEZ, LMOX, CMX, SISO and TOB, drug-melanin combined ratios ranged from 9.1% to 95.5% . SISO and TOB showed antibacterial activity reduction against E, Coli and B . Subtilis . The results suggest that melanin influences the intraocular dynamic mode of a new quinolone agent, NY-198, and that useful information about the influence of melanin in the drug dynamics of ocular tissues can be obtained from in vitro experiments. Acta Cient Venez, 1989, 40(4), 254 - 6 {Antibiotic activity of marine bacteria against human pathogenic bacteria}; Lodeiros C et al.; Its was analyzed the inhibition capacity of the marine bacteria that produce antibacterial substance in humans pathogenic bacteria, making use of direct antibiosis technique . The results showed that some these bacteria were able of to inhibit the growth of some humans pathogenic germs. Tr Inst Im Pastera, 1989, 66, 68 - 89, 171 {Ixodid ticks and rickettsia}; Rehacek J et al.; Ixodid ticks are an important link in the ecology of rickettsiae . Some tick species became specific vectors as well as reservoirs of certain species of rickettsiae ensuring their long lasting maintenance via interstadial and transovarial transmission often over generations in nature . To now many significant questions on relationship between ticks and rickettsiae became clear, however, most of them still remain to be elucidated . The open question, for instance, involves the data on the differences in sensitivity of various tick species to a certain species of rickettsiae what has its significance concerning the transmission of an agent to a host . Intracoelomal injection of a tick with rickettsiae does not solve its role as a vector in nature, because the main natural barrier of tick organism against pathogens, i.e . alimentary tract with its specific biochemical properties, has been avoided . To specify a tick as a vector of rickettsiae, data on their maintenance in various developmental stages of the arthropod as well as transmission to a host through feeding the blood are desirable . More attention should be focused to investigation on antibacterial (antirickettsial) effect of lysosyme, interferon and cellular elements in arthropods . Certainly mixed infections in ticks and namely their interactions, as well as the significance of rickettsia-like organisms in these arthropods, require also further investigations . Sufficient conclusive evidence concerning the effect of vector's organism on the biological properties of rickettsiae or in reverse, are almost unavailable . Investigations on above problems require the involvement of the modernest methods of immunology, immunochemistry, biochemistry and morphology. Lab Delo, 1989, (7), 65 - 6 {Determination of the bacteriocidal activity of the blood serum and lymph}; Slonim AA et al.; A microbiologic method for measurements of the blood serum and lymph bactericidal activity with the use of the test system with Bac . subtilis spore suspension and agar dosed for the nutrient and growth substances is suggested for clinical practice . These activities have been measured in patients with mammary carcinomas during surgical treatment; the levels of nonspecific antibacterial defense factors of the body have proved to be sufficiently high. Lab Delo, 1989, (5), 15 - 7 {Evaluation of the cationic-lysosomal test in patients with pneumonia against a background of therapy}; Domashenko ON et al.; The authors' findings evidence that measurements of cationic protein levels is a sufficiently informative test in the complex of investigations that help predict the course of acute pneumonia and the therapeutic efficacy of drugs stimulating the nonspecific resistance of the body . Combined therapy with the use of methyluracil and eleutherococcus is more effective for pneumonia patients than the complex including aloe and antibacterial and symptomatic agents alone. Lab Delo, 1989, (4), 51 - 5 {A method of reversed radial immunodiffusion and determination of diphtheria antibodies}; Shmeleva EA et al.; Measurements of precipitating antidiphtheria antitoxic and antibacterial antibodies in human blood sera, carried out by this new technique, have demonstrated higher levels of both antibody types in healthy adult vaccinees than in normal subjects who had contacts with diphtheria patients . Convalescents after diphtheria develop elevated levels of antitoxic and antibacterial antibodies, these levels growing to reach the concentrations similar to those in healthy vaccinees. J Biol Chem, 1988 Dec 25, 263(36), 19424 - 9 A family of bacteria-regulated, cecropin D-like peptides from Manduca sexta; Dickinson L et al.; Manduca sexta larvae respond to bacterial challenge by synthesizing a set of antibacterial hemolymph proteins . We have purified and sequenced three members of a family of cecropin D-like bactericidal peptides and isolated a cDNA clone complementary to a closely related bactericidin . Results obtained by Northern hybridization and RNase protection analysis showed that the increased synthesis of bactericidins is due to induction of their mRNA levels and that the synthesis of these peptides is not strictly tissue-specific, in contrast to previous beliefs . Although fat body was a richer source, the relative amounts of bactericidin mRNA were significant in seven other tissues examined. Int J Cancer, 1988 Dec 15, 42(6), 913 - 6 Nalidixic acid and oxolinic acid reversibly suppress 3-methylcholanthrene-induced cell transformation of BALB/3T3 mouse cells; Kaneko M et al.; The effects of nalidixic acid (Nal) and oxolinic acid (Oxl), synthetic antibacterial compounds that inhibit bacterial DNA gyrase, on 3-methylcholanthrene (MC)-induced transformation of BALB/3T3 mouse cells were investigated . Exposure of the cells to Nal or Oxl for 2 weeks at any time during 4 weeks of incubation following MC treatment suppressed MC-induced transformation . Nal and Oxl also suppressed the enhancement of transformation by 12-O-tetradecanoylphorbol-13-acetate (TPA) initiated by MC . The suppression of transformation by Nal was released by exposure of the cells to TPA after removal of Nal . Since the suppressive effects of Nal and Oxl on transformation were time-related, they may be due to epigenetic changes. Nippon Shishubyo Gakkai Kaishi, 1988 Dec, 30(4), 1141 - 55 {Topical application of the controlled release strips containing ofloxacin (PT-01) in periodontal therapy}; Okada H et al.; The association of periodontopathic bacteria in the subgingival plaque with human periodontal disease has been well established . However, past attempts at reducing the level of pathogenic bacteria by using antibiotics as well as other antibacterial substance, so far, have not been fully successful . In this study, the effect of topical application of ofloxacin (OFLX), a synthetic antibiotic, was evaluated in relation to the clinical parameters . For this purpose, the new developed controlled release strips containing OFLX (PT-01), in which there were structurally immediate- and sustained-releasing portions, were used . 147 adult patients suffering from moderate to severe periodontitis were selected for this study . The patients had received no periodontal treatment previously and had taken no antibiotics within the preceding 6 months . Three different sites with a deep probing pocket depth (greater than or equal to 5 mm) were randomly selected in each patient, and were divided into three groups, i.e., PT-01 applied site (T), placebo-applied site (P) and control site (C) . Periodontal treatments consisted of oral hygiene instruction and supragingival scaling on day 0 and 7, and subgingival scaling and root planing on day 14 . PT-01 was applied in the periodontal pocket weekly on day 0 to 35, and clinical parameters on each site were recorded weekly . The results showed that, during first 14 days, significant reduction in the percentage of the sites which showed bleeding on probing, pus discharge or mobility of the tooth was observed in the PT-01 applied site . However in placebo and/or control group, no significant change in any parameters was observed in this period . While, after subgingival scaling and root planing, significant improvement was found at all sites in every clinical parameter . Especially, PT-01 applied sites showed significant improvement in the gingival index and bleeding on probing, compared to placebo-applied or control sites . These results suggest that weekly insertion of PT-01 in the periodontal pocket along with the subgingival scaling and root planing could have significant effect on the improvements in the gingival inflammation . Taken together, weekly application of PT-01 might have ameliorating effect as adjuncts of mechanical subgingival plaque control in the periodontal treatment. Farmaco {Sci}, 1988 Dec, 43(12), 961 - 78 {Spectral and thermal characterization of cephalosporins . I . Cefadroxil and cefalexin}; Delarbre JL et al.; Cefadroxil and cefalexine were characterized by thermal and spectral analysis . A vibrational study by infrared and Raman spectroscopies was made to connect the structural data with the antibacterial activity. Am J Vet Res, 1988 Dec, 49(12), 2041 - 6 Pharmacokinetics, bioavailability, and in vitro antibacterial activity of rifampin in the horse; Wilson WD et al.; The pharmacokinetics and bioavailability of rifampin were determined after IV (10 mg/kg of body weight) and intragastric (20 mg/kg of body weight) administration to 6 healthy, adult horses . After IV administration, the disposition kinetics of rifampin were best described by a 2-compartment open model . A rapid distribution phase was followed by a slower elimination phase, with a half-life (t1/2{beta}) of 7.27 +/- 1.11 hours . The mean body clearance was 1.49 +/- 0.41 ml/min.kg, and the mean volume of distribution was 932 +/- 292 ml/kg, indicating that rifampin was widely distributed in the body . After intragastric administration of rifampin in aqueous suspension, a brief lag period (0.31 +/- 0.09 hour) was followed by rapid, but incomplete, absorption (t1/2{a} = 0.51 +/- 0.32 hour) and slow elimination (t1/2{d} = 11.50 +/- 1.55 hours) . The mean bioavailability (fractional absorption) of the administered dose during the first 24 hours was 53.94 +/- 18.90%, and we estimated that 70.0 +/- 23.6% of the drug would eventually be absorbed . The mean peak plasma rifampin concentration was 13.25 +/- 2.70 micrograms/ml at 2.5 +/- 1.6 hours after dosing . All 6 horses had plasma rifampin concentrations greater than 2 micrograms/ml by 45 minutes after dosing; concentrations greater than 3 micrograms/ml persisted for at least 24 hours . Mean plasma rifampin concentrations at 12 and 24 hours after dosing were 6.86 +/- 1.69 micrograms/ml and 3.83 +/- 0.87 micrograms/ml, respectively . We tested 162 isolates of 16 bacterial species cultured from clinically ill horses for susceptibility to rifampin.(ABSTRACT TRUNCATED AT 250 WORDS) Cell Immunol, 1988 Dec, 117(2), 369 - 77 Cytokine activation of antibacterial activity in human pulmonary macrophages: comparison of recombinant interferon-gamma and granulocyte-macrophage colony-stimulating factor; Jensen WA et al.; We examined the ability of two recombinant human cytokines, granulocyte-macrophage colony-stimulating factor (rHu-GM-CSF) and interferon-gamma (rHu-IFN-gamma) to activate antibacterial mechanisms in human pulmonary macrophages (PM) and peripheral blood monocytes (PBM) . Growth of Legionella pneumophila (LP) was assessed in PM or PBM which had been exposed to either rHu-IFN-gamma (500-1000 u/ml) or rHu-GM-CSF (1 to 10,000 u/ml) . In both PM and PBM exposed to 500 u/ml rHu-IFN-gamma, growth of LP was reduced compared to cells exposed to media alone . By comparison, exposure of these cell types to rHu-GM-CSF had no detectable effect on bacterial replication . In order to investigate potential mechanisms accounting for this observation, the effect of these cytokines on the hydrogen peroxide (H2O2)-releasing capacity of cells was studied . Exposure of PM and PBM to rHu-IFN-gamma (500 to 1000 u/ml) resulted in increased production of H2O2 triggered by phorbol myristate acetate; when subjected to the same experimental conditions, rHu-GM-CSF-exposed cells exhibited no increase in H2O2 production . To further clarify the role of rHu-IFN-gamma-induced augmentation of oxidative metabolism on cellular inhibition of bacterial growth, an amount of catalase capable of completely neutralizing extracellular H2O2 was added to cells before and during infection . This did not abrogate the antibacterial activity of rHu-IFN-gamma . These studies demonstrate that rHu-IFN-gamma but not rHu-GM-CSF is capable of augmenting the capacity of PM and PBM to restrict LP growth . These data suggest that the antibacterial activity of rHu-IFN-gamma in this system may involve oxidative as well as nonoxidative mechanisms. Antimicrob Agents Chemother, 1988 Dec, 32(12), 1879 - 86 Iron-regulated outer membrane proteins of Escherichia coli K-12 and mechanism of action of catechol-substituted cephalosporins; Curtis NA et al.; Selected aminothiazolyl-oxime cephalosporin congeners substituted at C-3' with a catechol moiety were used to probe the basis of the enhanced antibacterial activity against Escherichia coli K-12 often associated with chemical modifications of this type . Evidence is presented for a tonB-dependent illicit transport of the compounds across the outer membrane of E . coli K-12, the process involving jointly and specifically the Fiu and Cir iron-regulated outer membrane proteins . Thus, both tonB and fiu cir mutants showed a comparably reduced susceptibility to the probe compounds, whereas mutants singularly lacking any one of the six iron-regulated outer membrane proteins (Fiu, FepA, FecA, FhuA, FhuE, and Cir) or lacking any combination of any two of these proteins (except Fiu plus Cir) did not show this resistance . Mutants devoid of all six iron-regulated outer membrane proteins were no more resistant to the probe compounds than fiu cir or tonB strains . In addition to the latter genes, the products of the exbB and possibly the exbC loci were necessary for maximal antibacterial potency . A dependence of antibacterial activity on the level of expression of the uptake system components was noted . Comparison of penicillin-binding protein target affinity with antibacterial activity suggested a possible periplasmic accumulation of active compounds by E . coli K-12 . Free vicinal hydroxyl groups of the catechol residue were a primary chemical requirement for recognition by the uptake pathway and thus for high antibacterial activity. FASEB J, 1988 Dec, 2(15), 3083 - 6 In vivo glucose utilization by individual tissues during nonlethal hypermetabolic sepsis; Meszaros K et al.; Febrile sepsis was induced in rats by repeated s.c . injections of live Escherichia coli bacteria . Glucose utilization of different tissues was investigated in vivo by using the 2-deoxyglucose tracer technique . In septic rats the rate of glucose utilization was increased in macrophage-rich tissues, including the liver (2.7-fold), spleen (2.4-fold), and ileum (1.6-fold), compared with tissues from time-matched nonseptic animals . A smaller increase in glucose utilization was evident in the abdominal muscle (1.3-fold) and in the white portion of the quadriceps muscle (1.3-fold) . Changes were not significant in nine other tissues, including the brain . We postulate that in sepsis the mononuclear phagocyte system may be responsible for most of the increment of glucose utilization, and the latter provides metabolic support for the increased antibacterial activity of these cells. Acta Endocrinol (Copenh), 1988 Dec, 119(4), 481 - 7 Effect of norfloxacin, a new quinolone, on GABA modulation of TRH-induced TSH release from perifused rat pituitaries; Roussel JP et al.; The effect of the quinolone norfloxacin, a new antibacterial agent that is thought to induce convulsions in patients by inhibiting the binding of GABA, was tested on the two kinds of GABA A modulation of fTRH-induced TSH release from perifused rat pituitaries . Norfloxacin (50 mumol/l) was found to reverse the inhibitory effect of GABA (100 nmol/l) on the TSH release induced by TRH (10 nmol/l) . The ratio of induced over spontaneous release was 0.79 +/- 0.05 in the presence of GABA, and 2.32 +/- 0.18 when norfloxacin was added 15 min before GABA vs 2.59 +/- 0.09 in the control response to TRH . Norfloxacin was also able to reverse the potentiating effect of GABA (10 nmol/l): the TSH response was 6.56 +/- 0.94 in the presence of GABA alone vs 2.92 +/- 0.35 with norfloxacin plus GABA . Norfloxacin was also able to reverse the potentiation induced by isoguvacine, a specific GABA A agonist (6.15 +/- 1.14 in the presence of isoguvacine vs 2.99 +/- 0.54 with norfloxacin plus isoguvacine) . Our results suggest that norfloxacin may antagonize the effect of GABA via the two classes of GABA A receptor sites which differ in affinity and are responsible for the dual effect of GABA on the TRH-induced TSH secretion. J Am Vet Med Assoc, 1988 Nov 15, 193(10), 1289 - 91 Medical and surgical management of multiple organ infarctions secondary to bacterial endocarditis in a dog; Ellison GW et al.; A 6-year-old male Doberman Pinscher developed multiple organ infarctions secondary to vegetative endocarditis . Clinical signs included fever, nystagmus, head-tilt, inappetence, dehydration, hematuria, and dysuria . The dog was azotemic and anemic and had a high WBC count and high liver enzyme activities . Disseminated intravascular coagulation was diagnosed on the basis of thrombocytopenia and prolonged activated clotting times . Vegetative mitral valvular lesions were evident on M-mode echocardiography . The dog underwent diuresis with physiologic saline solution and was treated parenterally with antibacterial and anticoagulant agents . Surgery was performed to remove an infarcted kidney and an infarcted spleen and to relieve urethral obstruction caused by a large blood clot . Gram-positive cocci were noticed in the biopsy specimens . Mortality associated with organ infarctions secondary to bacterial endocarditis is high, and combined medical and surgical therapy is rarely reported . This dog survived and was alive 38 months after surgery. J Biol Chem, 1988 Nov 15, 263(32), 17117 - 21 Molecular cloning of cDNA for sapecin and unique expression of the sapecin gene during the development of Sarcophaga peregrina; Matsuyama K et al.; A cDNA clone for sapecin, an antibacterial protein produced by an embryonic cell line of Sarcophaga peregrina, was isolated and characterized . This clone was found to encode a precursor of sapecin consisting of 94 residues, with sapecin (40 residues) constituting its carboxyl-terminal half . RNA blot hybridization revealed that the gene for the sapecin precursor is activated in the hemocytes of the third instar larvae of Sarcophaga in response to body injury . Thus, sapecin is probably a defense protein synthesized by Sarcophaga to prevent bacterial infection through the damaged body wall . This gene was also found to be activated in the embryonic and early pupal stages, suggesting that sapecin also plays a role in the ontogenetic processes of Sarcophaga. J Biol Chem, 1988 Nov 15, 263(32), 17112 - 6 Purification of three antibacterial proteins from the culture medium of NIH-Sape-4, an embryonic cell line of Sarcophaga peregrina; Matsuyama K et al.; Three antibacterial proteins were purified from the culture medium of NIH-Sape-4, an embryonic cell line of Sarcophaga peregrina (flesh fly) . Sequencing studies showed that two of these proteins belong to the sarcotoxin I family, potent antibacterial proteins purified from the hemolymph of Sarcophaga larvae, whereas the other protein, named sapecin, is a new protein consisting of 40 amino acid residues including 6 cysteine residues . Unlike sarcotoxin I, sapecin preferentially represses the growth of various Gram-positive bacteria . The proteins of the sarcotoxin I family produced by this cell line were found to have carboxyl-terminal glycine, whereas sarcotoxin I in the hemolymph has amidated amino acids . This suggests that the embryonic cells lack an enzyme that cleaves off carboxyl-terminal glycine to form a new amidated carboxyl terminus. J Nat Prod, 1988 Nov-Dec, 51(6), 1178 - 83 Diterpenoids from the roots of Salvia hypargeia; Ulubelen A et al.; From the root extracts of Salvia hypargeia, in addition to the known diterpenoids cryptanol and horminone, six new abietane diterpenoids were isolated . The structures of the new and the known compounds were established by spectral data . The new compounds, hypargenins A, B, C, D, and F, showed antibacterial activity, while hypargenin F was also active against Mycobacterium tuberculosis . Hypargenin E did not exhibit antibacterial activity. Andrologia, 1988 Nov-Dec, 20(6), 521 - 5 Josamycin concentration in human ejaculate and its influence on sperm motility--a contribution to antibiotic therapy in andrological patients; Schramm P et al.; The concentration of josamycin was determined in the split ejaculate of 5 volunteers after oral administration for several days . One aim of this investigation was to examine the penetration of the macrolide antibiotic into the prostate and the seminal vesicles . 2.23 +/- 1.8 micrograms/ml josamycin was found in fraction I of the ejaculate, consisting mostly of prostatic secretion, and 1.56 +/- 1.37 micrograms/ml josamycin in fraction II comprising mainly secretions from the seminal vesicles . The concentrations of josamycin found in both fractions of the ejaculate are clearly comparable with serum levels of the antibiotic . Josamycin thus attains concentrations in the prostate and seminal vesicles which are effective against Mycoplasma and Chlamydia, pathogens of increasing importance in infections of the urogenital tract . In vitro studies on samples from 30 andrological patients showed that josamycin (0.5 micrograms/ml) did not impair, but even increased the motility of spermatozoa (p less than or equal to 0.01) . On the basis of these results josamycin is recommended for the treatment of andrological patients . In particular, the specific antibacterial spectrum also indicates the use of this antibiotic for treatment of the partner when children are desired . The usual precautionary measures for pregnancy must then be adhered to. J Chromatogr Sci, 1988 Nov, 26(11), 545 - 50 A collaborative study: high-pressure liquid chromatographic determination of carbadox and pyrantel tartrate in animal feeds; Thorpe VA; Carbadox (CBX), an antibacterial agent, and pyrantel tartrate (PT), an anthelmintic, are formulated either separately or together in swine feeds . The official Association of Official Analytical Chemists (AOAC) spectrophotometric methods for both drugs are long, nonspecific, and require standard addition techniques . Results by this technique are positively biased . A simple, direct, specific, high-pressure liquid chromatographic (HPLC) method to determine either one or both drugs simultaneously with apparent accuracy and precision is developed . Drugs are released from feed matrices by water, extracted with dimethylformamide (DMF), cleaned up on alumina, and quantitated by direct comparison to standards using a Whatman Partisil 10 ODS-3 column and a mobile solvent containing 23.5 +/- 1.5% DMF in phosphate buffer (pH 2.0) . Fourteen laboratories participated in a collaborative study of this method for determination of CBX and PT in animal feeds. Zentralbl Bakteriol Mikrobiol Hyg {A}, 1988 Nov, 270(1-2), 160 - 70 Antibacterial activity of selected tropones and tropolones; Saleh NA et al.; The antibacterial activity of 33 substituted and unsubstituted seven-member ring tropones and tropolones was examined on 14 reference strains representing Gram-positive and Gram-negative bacteria . It was shown that the chemical character and position of the substituent plays a distinct role in the biological activity of investigated compounds . Depending on the substituent the antibacterial effect may be either increased or diminished . C-1 thio and C-2 nitro derivatives of tropone are significantly more active than tropone . The dibenzotropone derivatives display no antibacterial activity . Hydroxymethyl derivatives of tropolone are more active than tropolone, while hydroxy-, isopropyl-, methyl- as well as tropolone acetates are equipotent. J Antibiot (Tokyo), 1988 Nov, 41(11), 1644 - 8 Erythromycin A 11,12-methylene acetal; Hunt E et al.; Erythromycin A 11,12-methylene acetal (5) and the corresponding 9-methoxime, 9-dihydro, and 8-hydroxy derivatives have been prepared and their antibacterial activities compared with those of erythromycin A and its 11,12-cyclic carbonate . The simple methylene acetal 5 showed excellent activity against Gram-positive organisms in vitro. Antimicrob Agents Chemother, 1988 Nov, 32(11), 1693 - 8 Antibacterial action of 2-bromo-2-nitropropane-1,3-diol (bronopol); Shepherd JA et al.; Patterns of growth inhibition of Escherichia coli in the presence of 2-bromo-2-nitropropane-1,3-diol (bronopol) indicate a period of biocide-induced bacteriostasis followed by growth at an inhibited rate . The length of the bacteriostatic period, but not the subsequent growth inhibition, was reduced by the addition of excess cysteine . Patterns of growth inhibition were unaffected by catalase or superoxide dismutase . The bactericidal concentrations (100 to 500 micrograms/ml) were considerably in excess of the MIC (13 micrograms/ml) and generally produced first-order reductions in viability . Bactericidal activity was considerably reduced by anoxic conditions and by the presence of catalase or superoxide dismutase . Results indicate that there are two distinct reactions between bronopol and thiols . Under aerobic conditions, bronopol catalytically oxidizes thiol-containing materials such as cysteine, with atmospheric oxygen as the final oxidant . By-products of this reaction are active oxygen species such as superoxide and peroxide, which are directly responsible for the bactericidal activity of the compound and for the reduced growth rate after the bacteriostatic period . The latter effect probably results from the oxidation of intracellular thiols such as glutathione and cysteine . Catalytic oxidation of thiols in the presence of excess thiol leads to the creation of an anoxic state . Under these conditions, the slower reaction with thiols, which consumes bronopol, predominates . Consumption of bronopol by its reaction with thiols, without the involvement of oxygen, leads to the eventual removal of bronopol from treated suspensions and the resumption of growth. Antimicrob Agents Chemother, 1988 Nov, 32(11), 1680 - 3 Sensitization by heat treatment of Escherichia coli K-12 cells to hydrophobic antibacterial compounds; Tsuchido T et al.; The sensitivities of intact and heat-injured cells of Escherichia coli K-12 to several antibacterial compounds were measured by the prolongation of growth delay . Cells exposed to sublethal heat became more sensitive to various hydrophobic compounds, such as medium-chain fatty acids, alkyl esters of p-hydroxybenzoic acid, and some kinds of antibiotics or dyes, than unheated cells; but there was a smaller or no increase in sensitivity to short-chain fatty acids, chloramphenicol, and vancomycin . The destruction by heat of a permeability barrier of the outer membrane may have sensitized the cells to hydrophobic compounds . The sensitization was much lower for a strain defective in lipopolysaccharide, which is important as a barrier against hydrophobic compounds. Zentralbl Bakteriol Mikrobiol Hyg {A}, 1988 Nov, 270(1-2), 138 - 44 {Criteria for the establishment of limits for antibacterial chemotherapy}; Linzenmeier G; The safety of patients asks for stringent standards when fixing limit values of the minimal inhibition concentration (MIC) in mg/l . It should be possible to recognize resistant bacterial strains with a low error on the basis of the recommendations of the bacteriological laboratory which are eventually important for therapy . Attention is drawn to the use of recognized methods such as DIN 58940 and 58944 and the participation in interlaboratory studies . Only such bacteria should be interpreted as "susceptible" whose MIC's are reliably below or, which is even better, much below the generally recognized average blood and tissue levels . Thus the break-points for the rating "susceptible" must be within the range of low variation . As a result, a few strains more would come within the "moderately susceptible" range . This would not exclude them from being selected if chemotherapy is performed with a correspondingly higher dosage (provided it is tolerated) . Information on the chances of a success of therapy is improved in this way . A generous interpretation of pharmacokinetic data will in the end be more to the patient's detriment . In addition, there are numerous factors determining success or failure of therapy which cannot be established in vitro so that it is advisable to fix laboratory parameters in a stringent manner like that applied in the annexes (evaluation steps) to parts 3 and 4 of DIN 58940. Rev Infect Dis, 1988 Nov-Dec, 10(6), 1182 - 6 Hansenula anomala fungemia; Haron E et al.; Fungi of the genus Hansenula have rarely been reported as pathogenic in humans . A case of catheter-related Hansenula anomala fungemia in a patient with acute leukemia in remission is presented, and the clinical features of 11 additional patients infected with Hansenula species are reviewed . The spectrum of disease with these organisms ranges from asymptomatic fungemia to life-threatening disseminated infection . Predisposing factors appear to be immunosuppression, use of intravenous devices, and previous treatment with antibacterial drugs . Clinical experience and limited in vitro susceptibility data show that amphotericin B remains the drug of choice in the treatment of hansenula infections. J Antibiot (Tokyo), 1988 Nov, 41(11), 1542 - 51 Metabolites of microorganisms . 247 . Phenazines from Streptomyces antibioticus, strain Tü 2706; Geiger A et al.; From a strain of Streptomyces antibioticus seven yellow phenazines were isolated . The antibacterially most active antibiotic was identified as (-)-saphenamycin, a second one with compound DC-86-Y (saphenic acid) . Three compounds were new: Saphenic acid methyl ether, 6-acetylphenazine-1-carboxylic acid and an inseparable mixture of fatty acid esters of saphenic acid . Two simple phenazines were phenazine-1-carboxylic acid (tubermycin B) and unsubstituted phenazine, which was isolated for the first time from a microorganism. Presse Med, 1988 Oct 26, 17(37), 1936 - 9 {Ceftazidime in the treatment of purulent meningitis}; Astruc J; Third generation cephalosporins have modified the first-line treatment of bacterial meningitis in adults and children . Among these compounds, ceftazidime has a particularly wide antibacterial spectrum, and clinical results have confirmed its superiority, notably in the treatment of meningitis caused by Pseudomonas spp . It is an excellent first-line empirical treatment while awaiting bacteriological results, but in view of the severity of these diseases and of the dangerous pathogens that are often involved, it seems preferable to combine ceftazidime with an aminoglycoside . Route of administration (systemic or in situ) and duration of treatment must be tailored to each individual case. Biochem Pharmacol, 1988 Oct 15, 37(20), 3915 - 21 Inter-individual variation of human blood N-acetyltransferase activity in vitro; Lindsay RM et al.; Inter-individual variation in the in vitro acetylation of the antibacterial drug sulphamethazine by human whole blood was studied using reverse phase HPLC . The mean (range) values of blood N-acetyltransferase activity in vitro were 0.50 (0.29-0.83) nmol per 10(9) red blood cells (rbc) (N = 23), 3.33 (2.22-5.27) nmol per 10(9) rbc (N = 27) and 9.36 (6.72-15.76) nmol per 10(9) rbc (N = 23) at initial sulphamethazine concentrations of 0.018 mM, 0.18 mM and 1.44 mM respectively . The mean (range) values of the initial rate of sulphamethazine acetylation at these substrate concentrations were 28.1 (20.9-35.0) pmol/hr per 10(9) rbc (N = 11), 0.26 (0.18-0.42) nmol/hr per 10(9) rbc (N = 19) and 0.91 (0.61-1.50) nmol/hr per 10(9) rbc (N = 14) respectively . The mean (range) half life of thermal inactivation of blood acetylation capacity at 50 degrees was 0.91 (0.59-1.27) min (N = 12) at an initial substrate concentration of 0.18 mM . In each of these cases, there was no significant differences between the values obtained using blood samples from rapid and slow acetylators . Intra-individual variation of blood N-acetyltransferase activity was studied in a single subject on 24 separate occasions during a two year period and was less than 10% at each of the three sulphamethazine concentrations studied . The correlation between the in vitro blood N-acetyltransferase activity of eight volunteers measured on two separate occasions at least 6 weeks apart was 0.84, 0.98 and 0.98 at initial sulphamethazine concentrations of 0.018 mM, 0.18 mM and 1.44 mM respectively . Increasing the acetyl-CoA concentration of blood samples from 4 subjects by 0.34, 0.85 and 1.67 mM significantly increased both the initial acetylation rate of sulphamethazine and the amount of acetylsulphamethazine produced after an incubation time of 24 hr (initial sulphamethazine concentration = 0.18 mM). Biochemistry, 1988 Oct 4, 27(20), 7620 - 9 The solution conformation of the antibacterial peptide cecropin A: a nuclear magnetic resonance and dynamical simulated annealing study; Holak TA et al.; The solution conformation of the antibacterial polypeptide cecropin A from the Cecropia moth is investigated by nuclear magnetic resonance (NMR) spectroscopy under conditions where it adopts a fully ordered structure, as judged by previous circular dichroism studies {Steiner, H . (1982) FEBS Lett . 137, 283-287}, namely, 15% (v/v) hexafluoroisopropyl alcohol . By use of a combination of two-dimensional NMR techniques the 1H NMR spectrum of cecropin A is completely assigned . A set of 243 approximate interproton distance restraints is derived from nuclear Overhauser enhancement (NOE) measurements . These, together with 32 distance restraints for the 16 intrahelical hydrogen bonds identified on the basis of the pattern of short-range NOEs, form the basis of a three-dimensional structure determination by dynamical simulated annealing {Nilges, M., Clore, G.M., & Gronenborn, A.M . (1988) FEBS Lett . 229, 317-324} . The calculations are carried out starting from three initial structures, an alpha-helix, an extended beta-strand, and a mixed alpha/beta structure . Seven independent structures are computed from each starting structure by using different random number seeds for the assignments of the initial velocities . All 21 calculated structures satisfy the experimental restraints, display very small deviations from idealized covalent geometry, and possess good nonbonded contacts . Analysis of the 21 converged structure indicates that there are two helical regions extending from residues 5 to 21 and from residues 24 to 37 which are very well defined in terms of both atomic root mean square differences and backbone torsion angles . For the two helical regions individually the average backbone rms difference between all pairs of structures is approximately 1 A . The long axes of the two helices lie in two planes, which are at an angle of 70-100 degrees to each other . The orientation of the helices within these planes, however, cannot be determined due to the paucity of NOEs between the two helices. Ann Plast Surg, 1988 Oct, 21(4), 388 - 91 The use of maggots in wound debridement; Reames MK et al.; Since antiquity, clinicians have observed that maggots can provide debridement of necrotic wounds, but the therapeutic use has declined since the advent of aseptic wound management and antibiotics . In certain difficult wounds, the use of maggots for debridement may have a role . If so, the larvae must be prepared prospectively to control the bacterial population of the insect's intestinal tract and integument . The mechanism of wound debridement by maggots includes the secretion of proteolytic enzymes and antibacterial substances . A case of infestation of a necrotic wound in a patient with cancer of the head and neck is presented including the entomological identification and description of the maggots. Jpn J Antibiot, 1988 Oct, 41(10), 1370 - 84 Reproductive studies of NY-198 in rats . III . Perinatal and postnatal study; Tesh JM et al.; Lomefloxacin (NY-198), a new antibacterial agent, was administered daily by gavage to groups of 22 pregnant female rats of the CD strain at dosages of 30, 100 or 300 mg/kg/day from Day 17 of gestation to Day 21 of lactation . Females were allowed to deliver their litters and the offspring were examined for growth and functional development . There was a slight maternal response at the highest dosage (300 mg/kg/day), including increased salivation after dosing, reduced food intake in the treated period of gestation and increased water intake during the lactation period . Gestation length was slightly increased, although remaining within the laboratory background control range; in consequence, body weight of F1 offspring at Day 1 post partum was slightly increased . At 100 mg/kg/day, a few females showed increased salivation after dosing and there was a slight increase in gestation length . Birth weight of F1 offspring was slightly increased at 30 and 100 mg/kg/day but all values were within laboratory background control ranges . The survival, functional responses and fertility of F1 offspring were essentially unaffected by NY-198 . On the basis of the above results, 30 mg/kg/day was considered to be the no-effect level for the F0 females treated during late gestation and lactation whilst 300 mg/kg/day administered to the F0 females had no adverse effect upon their offspring. Jpn J Antibiot, 1988 Oct, 41(10), 1352 - 69 Reproductive studies of NY-198 in rats . II . Teratology study; Tesh JM et al.; Lomefloxacin (NY-198), a new antibacterial agent, was administered daily by gavage to groups of 32 pregnant female rats of the CD strain at dosages of 30, 100 or 300 mg/kg/day from Day 7 to Day 17 of gestation . Twenty-one females in each group were killed on Day 20 of gestation for examination of their uterine contents . Eleven females in each group were allowed to deliver their litters and the offspring were examined for growth and functional development . At the highest dosage (300 mg/kg/day), there was a small reduction in maternal weight gain and a transient reduction in food intake during the treatment period . Foetal and placental weights were markedly reduced . However, survival, growth and development of F1 offspring were unaffected and, with the possible exception of a slight reduction in F2 foetal weight, their reproductive performance was unimpaired . At the intermediate level (100 mg/kg/day), maternal body weight gain and food intake during the treatment period were slightly reduced but, with this exception, the performance of F0 females and of the F1 generation was essentially similar to that of the vehicle controls . At the lowest dosage (30 mg/kg/day), no adverse effects were recorded on either the F0 females or the F1 generation . On the basis of the above results 30 mg/kg/day was considered to be the no effect level for the F0 females treated during gestation while 100 mg/kg/day administered during gestation to F0 females had no effect upon performance of the F1 generation. Jpn J Antibiot, 1988 Oct, 41(10), 1341 - 51 Reproductive studies of NY-198 in rats . I . Fertility study; Tesh JM et al.; Lomefloxacin (NY-198), a new antibacterial agent, was administered daily by gavage to groups of 22 male and 22 female rats at dosages of 30, 100 or 300 mg/kg/day . Males were dosed for 71 days before pairing and then until termination, and females were dosed for 15 days before pairing, throughout mating and until Day 7 of gestation . Females were killed on Day 20 of gestation for examination of their uterine contents . Males were killed after approximately 14 weeks treatment and their reproductive organs were weighed and retained . At 300 mg/kg/day the majority of animals showed increased salivation, water intake was slightly increased throughout the treatment period in males and before pairing in females whereas food intake showed a slight, transient reduction during the first few days of treatment in both sexes . Body weight gain of males was marginally depressed during the first week of treatment, but no other signs of reaction to treatment were observed . At 30 and 100 mg/kg/day some animals exhibited increased salivation after being dosed . At all dosages, NY-198 was without adverse effects upon mating performance and fertility, or upon survival, growth and development in utero . On the basis of the above results it is considered that the no effect level with respect to reproduction and breeding performance of treated F0 animals and the in utero development of the foetuses was 300 mg/kg/day . A dosage of 100 mg/kg/day was considered to be the no effect level for somatic changes in the F0 animals, and even at the highest dosage of 300 mg/kg/day only slight effects were recorded on the F0 animals. Appl Environ Microbiol, 1988 Oct, 54(10), 2532 - 5 Antibacterial activity of soluble pyridinium-type polymers; Kawabata N et al.; Cross-linked poly(N-benzyl-4-vinylpyridinium halide) (designated insoluble BVP) was previously reported to capture bacterial cells alive by contact with them . The corresponding linear polymer poly(N-benzyl-4-vinylpyridinium salt) (designated soluble BVP) was found to exhibit antibacterial activity . This soluble pyridinium-type polymer showed strong antibacterial activity against gram-positive bacteria, whereas it was less active against gram-negative bacteria . The antibacterial activity of this cationic, polymeric disinfectant was considerably greater than that of the corresponding monomeric compound and was approximately equal to that of conventional disinfectants such as benzalkonium chloride and chlorohexidine. J Antibiot (Tokyo), 1988 Oct, 41(10), 1430 - 8 Synthesis and antibacterial activity of N-acyl vancomycins; Nagarajan R et al.; Several glycopeptides containing N-acyl groups have been isolated recently . We undertook the synthesis of N-acyl vancomycins, using the active ester method . The in vitro and in vivo antibacterial activity were evaluated, and structure-activity relationship of this series of semisynthetic vancomycins is discussed. J Antibiot (Tokyo), 1988 Oct, 41(10), 1395 - 408 Synthesis and structure-activity relationships in the cefpirome series . II . Analogues of cefpirome with different 7-heteroarylacetamido and 3'-ammonium substituents; Lattrell R et al.; The synthesis and antibacterial activity in vitro of 7-(2-heteroarylacetamido)-3-{(2,3- cyclopentenopyridinium)methyl}cephalosporins and of some related compounds with different ammonium functions in 3'-position are described . The 7-{5-amino-1,2,4-thiadiazol-3-yl} and the 7-{4-aminopyrimidin-2-yl} analogues of cefpirome and compounds with 3-aliphatic ammoniummethyl functions have excellent antibacterial activity . Cephalosporins with different N-heterocycles other than pyridine in 3'-position are less active than their 3-pyridiniummethyl analogues . Attachment of a pyridinium group to a cephem at C-3 via a thiomethyl or an aminomethyl bridge causes reduction of antibacterial activity. J Antibiot (Tokyo), 1988 Oct, 41(10), 1316 - 30 O-demethylpaulomycins A and B, U-77,802 and U-77,803, paulomenols A and B, new metabolites produced by Streptomyces paulus; Argoudelis AD et al.; O-Demethylpaulomycin A (C33H44N2O17S), O-demethylpaulomycin B (C32H42N2O17S), paulomenol A (C29H43NO16), paulomenol B (C28H41NO16), and the hydrogen sulfide adducts of paulomycin A (U-77,802, C34H48N2O17S2), and paulomycin B (U-77,803, C33H46N2O17S2) have been isolated from fermentations of Streptomyces paulus strain 273 . The structure of these compounds was determined by 1H and 13C NMR and fast atom bombardment mass spectrum spectroscopic techniques and degradative studies . The antibacterial properties of these new metabolites, which are related to paulomycins A and B (J . Antibiotics 35: 285-294, 1982), are briefly discussed. Toxicology, 1988 Oct, 51(2-3), 255 - 66 Formation of methemoglobin by photoactivation of nitrofurantoin or of 5-nitrofurfural in rats exposed to UV-A light; Busker RW et al.; The antibacterial drug nitrofurantoin (NFT) is notorious for causing hemolytic anemia, which may be related to the methemoglobinemia, another side-effect of NFT . As NFT is photolabile, and nitrite, well known as a MetHb generator, is an important photoproduct of NFT, it seems not unlikely that light is a cause of NFT-induced MetHb formation . When rats were irradiated with UV-A immediately after oral NFT administration, the amount of MetHb significantly increased: 0.97 +/- 0.37% n = 36 (P less than 0.001 Student's t-test, control value: 0.5%) . An increase in MetHb was also observed with rats simultaneously exposed to UV-A and the major photodecomposition product of NFT, viz . 5-nitrofurfural . In addition in vitro experiments proved the formation of MetHb as a result of photoactivation of NFT . Nitrite, photochemically formed from nitrofurfural and from the metabolite nitrofuroic acid, plays an important role . A dark reaction of the other photoproduct, nitrofurfural, with hemoglobin also appeared to cause a considerable amount of MetHb in vitro . However, because of rapid deactivation of nitrofurfural by either photodecomposition or metabolism, this dark reaction is not expected to contribute to the in vivo MetHb formation. J Med Chem, 1988 Oct, 31(10), 2004 - 8 New "ofloxacin" type antibacterial agents . Incorporation of the spiro cyclopropyl group at N-1; Kiely JS et al.; The first example incorporating a spiro cyclopropyl group into an "ofloxacin" type of quinolone antibacterial agent has been prepared by potassium fluoride mediated ring closure of the hydroxymethyl cyclopropyl intermediate to give 9'-fluoro-7'-oxo-10'-(1-piperazinyl)spiro{cyclopropane-1,3'(2'H)-{7H} pyrido{1,2,3-de}{1,4}benzoxazine}-6'-carboxylic acid . Analogues were made by substitution at C-7 by various complex amines . Evaluation of these compounds for antibacterial activity was carried out . All examples prepared and examined showed in vitro minimum inhibitory values and in vivo mouse protection results to be diminished as compared to the parent, ofloxacin. J Med Chem, 1988 Oct, 31(10), 1987 - 93 Oral absorption of cephalosporin antibiotics . 1 . Synthesis, biological properties, and oral bioavailability of 7-(arylacetamido)-3-chloro cephalosporins in animals; Kukolja S et al.; A number of 7-(arylacetamido)-3-substituted cephalosporins were prepared and tested in animals for oral absorbability . Bioavailability in mice, rats, dogs, and monkeys was determined after oral or parenteral administration . Oral bioavailability of five compounds selected for more intensive study was generally higher than that of penicillin V in all species tested . The results of ED50 testing against experimental infections in mice generally supported the bioavailability studies . Antibiotic activities were evaluated against Gram-positive and Gram-negative organisms with some derivatives expressing in vitro activity similar to cefaclor . The plasma half-life in rats was relatively short and the plasma curves were strongly influenced by probenecid, indicating rapid renal secretion . Some 7-(arylacetamido)-3-chloro cephalosporins are orally absorbed in animals to a greater extent than penicillin V, and antibacterial agent of proven clinical utility. Chest, 1988 Oct, 94(4), 745 - 9 Bronchoalveolar lavage in the diagnosis of pulmonary infiltrates in patients with acute leukemia; Saito H et al.; The utility of bronchoalveolar lavage (BAL) in determining the causative agent of pulmonary infiltrates in patients with acute leukemia is not known . We retrospectively evaluated the diagnostic yield of BAL in 22 adults with acute leukemia and compared the results with those at autopsy performed within three weeks of BAL . All patients had neutropenia and thrombocytopenia at the time of BAL, were receiving broad-spectrum antibacterial agents, and 15 were also receiving amphotericin B before BAL . The median interval between the detection of pulmonary infiltrates and BAL was seven days (range, 0 to 23 days); the median interval between BAL and autopsy was nine days (range, 1 to 20 days) . The diagnostic yield of BAL was 15 percent (3 of 20 specific diseases); all three were Candida pneumonia . The sensitivity of BAL was 75 percent and its specificity 100 percent, for Candida pneumonia . BAL did not result in a specific diagnosis for the 17 remaining diseases, nine of which were Aspergillus pneumonia . In seven patients in whom autopsy was performed within 72 hours of BAL, lavage results correlated with those of autopsy in only one who had Candida pneumonia . All BAL cultures were falsely positive, except in four cases of Candida pneumonia . The therapeutic regimen was not modified according to the BAL results in any of the 22 patients . There were no major complications associated with the procedure. Chemioterapia, 1988 Oct, 7(5), 336 - 40 Infectious diarrhea in the aged: controlled clinical trial of rifaximin; Della Marchina M et al.; The effectiveness and tolerance of a new non-absorbable antibiotic, was evaluated on 121 aged patients affected with severe bacterial diarrhea . A double-blind design vs placebo was followed . The drug (three 200 mg tablets/die for 7 days) proved effective in reducing the number of daily discharges and the seriousness and duration of symptoms, as compared to placebo . Its antibacterial activity was furthermore confirmed by coprocultures: only 16/75 bacterial strains were still detectable after therapy, against 33/70 in the placebo group . Tolerance to rifaximin, both local and systemic, proved to be excellent. Pediatr Med Chir, 1988 Sep-Oct, 10(5), 467 - 70 {Criteria for selecting antibacterial drugs for use in newborn infants}; Vigano A et al.; During the last years many advancements have been made in the field of clinical pharmacology . Nowadays we have a better understanding of the factors influencing absorption, distribution and elimination of antibacterial drugs in the newborn . However many problems have not been faced yet; of primary importance are earliness and aiming of therapy . Much has been written about the use of hematologic screening tests for an early diagnosis of sepsis and the use of tests for a rapid etiologic diagnosis . This is probably the result not only of the commonly encountered difficulty in making a clinical diagnosis of sepsis (based on clinical findings that are often insidious and aspecific) but also of the implications concerning either a "non-diagnosis" or a large use of antibacterial drugs . The choice of an appropriate antibacterial therapy in the newborn with sepsis implies a careful interpretation of the data concerning: 1) bacterial epidemiology and 2) sensitivity towards drugs of the bacterial most commonly identified in sepsis . For that purpose, it is important to distinguish between early and late sepsis and between the etiological agents more frequently responsible for the first and those for the later . Moreover it is important to consider the role of rapid tests in the etiological diagnosis, as a guide to the modification of the initial empirical therapy. Vestn Khir Im I I Grek, 1988 Sep, 141(9), 49 - 52 {Selection of the method of treatment of suppurative spinal epiduritis}; Fadeev BP; The author has analyzed 65 observations of patients with purulent spinal epiduritis resulting mostly from purulent diseases of the skin and subcutaneous fat . A period of pyo-resorptive fever was established which in most cases preceded the appearance of local symptoms of the disease . The purulent process is more frequently accompanied with fever, more rarely it turns into sepsis . The most rational method of treatment of the disease is early operation followed by irrigative drainage of the wound in complex with antibacterial and symptomatic therapy . A classification of purulent spinal epidurites is proposed. Farmaco {Sci}, 1988 Sep, 43(9), 677 - 91 {A substance with antibacterial and antifungal activity . V . Synthesis and microbiological activity of new derivatives of 1,5-diarylpyrrole}; Scalzo M et al.; The synthesis and antifungal activities of new 1,5-diarylpyrrole derivatives are reported . The N-methylpiperazinyl substituent must be regarded as fundamental to activity . Furthermore the presence of substituents on the para position of the two phenyl rings and the presence of halogen atoms can be considered strengthening factors to microbiological activity . The results obtained are discussed on the basis of structure-activity relationship. Antimicrob Agents Chemother, 1988 Sep, 32(9), 1456 - 7 Antibacterial effect of etoposide in vitro; Calame W et al.; Etoposide, an antitumor drug, had an effect in vitro against all strains of gram-positive bacteria studied but not against three gram-negative bacteria . The MICs ranged between 6.2 and 50 micrograms/ml . In short-term-growth experiments, etoposide had a bactericidal efficacy that was 10 to 50 times lower than that of cloxacillin. J Burn Care Rehabil, 1988 Sep-Oct, 9(5), 476 - 81 Cross-linked silver-impregnated skin for burn wound management; Ersek RA et al.; Biological skin is effective in restoring the missing water vapor barrier and promoting healing in burn wounds . Its effectiveness in wound management has been limited, however, by its inherently limited antibacterial properties and the fact that it is sometimes rejected before healing is complete, even reversing previous beneficial effects . Limited availability and storage difficulties have posed further problems . Impregnation of biological skin with silver ions has been proven to provide a potent bactericidal effect directly at the wound surface . We hypothesized that aldehyde cross-linking of silver-impregnated skin would mask the histocompatibility sites from the recipient's immune system . This has been demonstrated previously with aldehyde cross-linking of allografts and xenografts, prolonging retention sufficiently to permit complete wound healing . Commercially available skin was treated with an aldehyde compound and impregnated with silver . Initial studies of this cross-linked skin for treatment of burn wounds showed average retention to be between 117 and 161 days, far exceeding that of any untreated skin . It was subsequently found that the aldehyde cross-linking permitted impregnation with higher concentrations of silver than had previously been possible--2,600 to 2,830 ppm as compared to an average of 1,020 to 1,350 ppm in previously available silver-impregnated skin . This results in a more potent, immediate antibacterial effect at the wound surface and an extended period of time-release antibacterial action before the silver is exhausted . The antibacterial properties of this aldehyde cross-linked silver-impregnated skin are effective in decontaminating even grossly infected wounds and in protecting against contamination of clean wounds from adjacent infected areas or external sources.(ABSTRACT TRUNCATED AT 250 WORDS) Am J Obstet Gynecol, 1988 Sep, 159(3), 570 - 3 Steady-state cord and amniotic fluid ceftizoxime levels continuously surpass maternal levels; Fortunato SJ et al.; As part of our management protocol for preterm premature rupture of membranes, ceftizoxime and tocolysis were used to prolong the latent period and prevent or treat concomitant infection . Ceftizoxime was selected for this protocol based on its physiochemical properties, which favor placental transfer of the drug . Patients achieving steady-state pharmacodynamics (more than three doses of the drug) were considered eligible for study . Ceftizoxime levels were determined by reverse-phase high-pressure liquid chromatography . All levels measured after the first hour of treatment were indicative of the relative concentration of ceftizoxime in the fetal and amniotic fluid compartments when compared with the maternal compartment . Mean (+/- SEM) ceftizoxime levels were 11.96 + 2.35 micrograms/ml in maternal serum, 24.54 +/- 4.78 micrograms/ml in cord serum, and 43.45 +/- 4.97 micrograms/ml in amniotic fluid . Based on its broad antibacterial activity and its high concentration in fetal blood and amniotic fluid, ceftizoxime appears to be an ideal agent for treatment of the intrauterine environment. Biochimie, 1988 Sep, 70(9), 1185 - 95 Structure and spatial conformation of the iron-binding sites of transferrins; Legrand D et al.; Transferrins are iron-binding glycoproteins involved in iron metabolism and antibacterial defense mechanisms . Since the discovery of transferrins, many studies have attempted to characterize the iron ligands and to establish the conformation of the iron-binding sites . From chemical and spectroscopic studies, it was generally accepted that iron was hexacoordinated to Tyr and His residues, to a water molecule and to a (bi)carbonate ion, electrostatically linked to an Arg residue . On the basis of these studies, on the one hand, and on the basis of the homologies between the amino acid sequences of transferrins, on the other hand, predicted data have been provided about the number and location of the iron ligands . Recent X-ray crystallography studies of human lactotransferrin have partially confirmed the above-mentioned predicted data and have brought invaluable information about the nature of the ligands and the conformation of the iron-binding site . On the basis of the obtained results, a scheme has been proposed in which the iron is coordinated to 2 Tyr, 1 His and 1 Asp residues, to a (bi)carbonate linked to an Arg residue and probably to a water molecule . The iron-binding site is located at the interface between the two domains which constitute each lobe of the transferrins. J Antibiot (Tokyo), 1988 Sep, 41(9), 1212 - 22 Structural relationships between senfolomycins and paulomycins; Argoudelis AD et al.; Senfolomycins A and B (Antimicrob . Agents Chemother.-1965: 828-831, 1966) are two antibacterial agents with physico-chemical and biological properties similar to those of paulomycin . Recent studies indicate that senfolomycin A (C29H36N2O16S, MW 700) has molecular composition and fast atom bombardment MS fragmentation pattern identical to those of paulomycin E . Extensive NMR work indicates that the two antibiotics, which have been separated by HPLC and TLC, differ only in the stereochemistry of the OCH3 group present in their respective sugar moieties . Indirect evident suggests that senfolomycin B is dihydrosenfolomycin A (C29H38N2O16S, MW 702) and in this respect it is related to paulomycin F . The proposed structures for senfolomycins A and B are discussed. J Med Chem, 1988 Sep, 31(9), 1772 - 8 Phosphinic acid inhibitors of D-alanyl-D-alanine ligase; Parsons WH et al.; We report the synthesis of a series of phosphinic acid dipeptide analogues, NH2CH(R1)PO(OH)CH2CH(R2)CO2H, related to DAla-DAla . The best of these compounds are potent, essentially irreversible inhibitors of DAla-DAla ligase, and their preferred stereochemistry was shown by chiral synthesis of (1(S)-aminoethyl)(2(R)-carboxy-1-n-propyl)phosphinic acid, 12b, and by X-ray crystallography of its derivative benzyl {1(S)-{(benzyloxycarbonyl)-amino}ethyl}(2(R)-carbomethoxy-1-propyl) phosphinate, 13, to correspond to the stereochemical configuration of DAla-DAla at both centers . A mechanism for the inhibition of DAla-DAla ligase by these compounds is proposed to involve an ATP-dependent formation of phosphorylated inhibitor within the enzyme's active site . The antibacterial activities of these compounds are modest although their spectra include both Gram-positive and Gram-negative susceptible organisms . The best antibacterial activity was shown by (1(S)-aminoethyl) {2-carboxy-2(R)-(methylthio)-1-ethyl}phosphinic acid, 3e, whose MIC's range from 4-128 micrograms/mL on nine of a panel of 11 bacterial organisms . Combination of one of the more active phosphinic acids 12b with the alanine racemase inhibitor fluoro-D-alanine enhances the antibacterial spectrum of the latter on several strains of bacteria and inhibits fluoro-D-alanine's self-reversal, which normally occurs at concentrations several fold higher than its MIC level . This inhibition of fluoro-D-alanine self-reversal is consistent with an involvement of DAla-DAla ligase inhibition in the antibacterial activity of these compounds. Pathol Biol (Paris), 1988 Sep, 36(7), 912 - 4 {Initial antibacterial prophylaxis after bone marrow allograft . Pilot study with systemic vancomycin}; Rubie H et al.; In 22 consecutive patients treated by allogenic bone marrow transplantation, the authors report their experience in complete gastrointestinal decontamination and prophylactic systemic vancomycin . Neither septicemia from the low digestive tract nor with Gram positive is noticed . A child developed septicemia with Capnocytophaga ochracea, resistant to vancomycin . There is no infectious death in this study and no significative toxicity is reported. Arch Intern Med, 1988 Sep, 148(9), 2066 - 7 Herpes simplex lymphangitis . Two cases and a review of the literature; Sands M et al.; Lymphangitis and lymphedema are rarely reported complications of herpetic hand or genital infection . The natural history of these complications is gradual resolution over 14 to 21 days . Recognition of this presentation of herpes infection avoids unnecessary surgery and antibacterial therapy . Antiviral therapy may have a role in shortening the duration of symptoms and aborting recurrent lymphangitic episodes. Br J Clin Pharmacol, 1988 Sep, 26(3), 295 - 301 The influence of ipratropium bromide and sodium cromoglycate on benzalkonium chloride-induced bronchoconstriction in asthma; Miszkiel KA et al.; 1 . Benzalkonium chloride, an antibacterial preservative that is added to nebuliser solutions, has been shown to cause bronchoconstriction when inhaled by asthmatic subjects . 2 . To investigate the potential role of reflex and mast cell-dependent mechanisms in the pathogenesis of bronchoconstriction produced by benzalkonium chloride we examined the effects of ipratropium bromide and sodium cromoglycate on this response in both concentration-response and time-course studies in nine asthmatic subjects . 3 . Pretreatment with inhaled ipratropium bromide (1 mg) and sodium cromoglycate (40 mg) displaced the benzalkonium chloride concentration-response curves to the right by a mean 2.2 fold and 3.1 fold respectively . 4 . Ipratropium bromide and sodium cromoglycate markedly attenuated the airway response to benzalkonium chloride throughout the 45 min time course period, inhibiting the overall response by 56% and 78% respectively . 5 . We conclude that benzalkonium chloride provokes bronchoconstriction in asthmatic subjects through a combination of mast cell activation and stimulation of peripheral and central neural pathways. J Rheumatol Suppl, 1988 Sep, 16, 1 - 4 History of enteric coated sulfasalazine in rheumatoid arthritis; Pinals RS; Sulfasalazine was synthesized almost 50 years ago specifically to treat rheumatoid arthritis . At that time bacterial infection was believed to be an important factor in pathogenesis . The linkage of sulfapyridine and salicylate with an azobond was viewed as a method of combining antibacterial and antiinflammatory actions while minimizing gastric irritation . Early therapeutic results were encouraging, but the drug was discarded as an antirheumatic agent for 30 years, until its serendipitous rediscovery . Subsequent controlled trials have confirmed its efficacy, which may be related to sulfasalazine itself or to the sulfapyridine moiety. Vopr Med Khim, 1988 Sep-Oct, 34(5), 107 - 10 {Enzymatic production of superoxide by human polymorphonuclear leukocytes in burns}; Karelin AA et al.; Production of superoxide anion by polymorphonuclear leukocytes (PMNL) was studied in donors and patients with burns . N-formyl-L-Met-L-Leu-L-Phe (FMLP) was used as an activator of PMNL . Evaluation in production of superoxide anion, caused by the activating effect of FMLP, proved to be useful as a diagnostic and prognostic criterion . 56 preparations of blood were studied in 21 patients with burns within the periods of acute burns toxemia, burns septicotoxemia and convalescence . Superoxide anion generating activity correlated with the disease severity: content of superoxide anion was distinctly decreased within the period of sepsis development . At the same time, complex treatment of the patients, involving step-by-step autodermoplastics, antibacterial preparations and immunotherapy, enabled to restore the superoxide anion production up to normal values . Evaluation of the superoxide anion generating activity by PMNL in the patients with severe forms of burns enabled to estimate the state of cell immunity in the patients depending on severity of burns trauma, period of burn disease and adequacy of the treatment applied. J Med Chem, 1988 Sep, 31(9), 1694 - 7 Synthesis and bacterial DNA gyrase inhibitory properties of a spirocyclopropylquinolone derivative; Wentland MP et al.; A novel conformationally restricted 1-cyclopropylquinolone (1) that incorporates structural features of both ofloxacin and ciprofloxacin has been prepared . Compound 1 was found to be a DNA gyrase inhibitor having potency similar to ofloxacin but less than ciprofloxacin . The cellular inhibitory and in vivo antibacterial potencies of 1 were found to be less than those of the two reference agents. Gut, 1988 Aug, 29(8), 1134 - 51 Cleaning and disinfection of equipment for gastrointestinal flexible endoscopy: interim recommendations of a Working Party of the British Society of Gastroenterology; Atropine inhibits the degranulation of Paneth cells in ex-germ-free mice; Department of Anatomy, Asahikawa Medical College, JapanPrevious studies have shown that the secretory products of Paneth cells contain antibacterial agents (lysozyme, IgA) that are affected by the bacterial milieu in the intestine . To investigate whether Paneth-cell secretion is controlled via cholinergic mechanisms, the ultrastructure of Paneth cells was studied in four animal groups: (1) germ-free (GF) control mice (Jcl: ICR {GN}, male, 13 weeks old), (2) GF mice injected subcutaneously with atropine sulfate (200 mg/kg body weight, dissolved in physiological saline 20 mg/ml), (3) ex-GF mice inoculated with feces from specific-pathogen-free (SPF) mice, and (4) ex-GF mice injected with atropine and inoculated with feces from SPF mice . In ex-GF mice inoculated with feces, 70-90% of the Paneth cells showed fewer secretory granules than those from GF mice (p less than 0.01) . Approximately 30% of the Paneth cells had a large vacuole (3-10 micron diameter) in the apical cytoplasm . Exocytosed electron-dense material from secretory granules was observed in a few crypt lumens . In ex-GF mice inoculated with feces and given atropine, about 90% of the Paneth cells contained numerous secretory granules, like those in GF control mice, but vacuolated Paneth cells and exocytotic figures were rare; thus the secretion of Paneth cells was blocked by atropine . It is therefore possible that the bacterial milieu in the intestine affects the secretory activity of Paneth cells via cholinergic mechanisms. Trop Anim Health Prod, 1988 Aug, 20(3), 130 - 6 Efficacy of parvaquone in the treatment of naturally occurring theileriosis in cattle in Iraq; Hawa N et al.; Parvaquone was tested in cattle infected with Theileria annulata when they were presented at clinics in the vicinity of Baghdad . Out of over 200 cases presented with suspected theileriosis between July 1984 and July 1985, the drug was used in 45 cases where theileriosis was confirmed by microscopic examination of blood and lymph node biopsy smears . Twenty seven of the cases were considered mild and 18 cases severe . Weights of the cattle were estimated and parvaquone was administered by intramuscular injection at a nominal dose of 20 mg/kg . A single treatment with parvaquone was used in 25 cases and 20 cases were treated twice but there was no correlation between severity of disease and the number of treatments given . Twelve cases (27%) also received antibacterial therapy . All cases were in exotic cattle or cattle born from exotic (imported) cattle and 64% of the cases were in cattle under six months of age . Temperatures dropped immediately after treatment and the majority were normal (below 39.5 degrees C) by two to three days after the first treatment . Of the 45 cases treated 43 recovered . This compares very favourably with a previously reported mortality of 66% in untreated imported cattle in Iraq. Am J Infect Control, 1988 Aug, 16(4), 173 - 7 Comparative antibacterial efficacy of a 2-minute surgical scrub with chlorhexidine gluconate, povidone-iodine, and chloroxylenol sponge-brushes; Aly R et al.; Chlorhexidine gluconate (Hibiclens), povidone-iodine (E-Z Scrub 201), and chloroxylenol (ParaSoft) sponge-brushes were compared for antibacterial efficacy in 2-minute surgical scrubs . Thirty-nine volunteers completed a 7-day baseline period and a 5-day treatment period . Thirteen participants were assigned to a chlorhexidine group, 12 to a povidone-iodine group, and 14 to a chloroxylenol group . Subjects followed a standardized protocol, performing 11 scrubs during the treatment period . Bacterial counts were taken by the glove-juice procedure immediately after scrubbing and at 3 and 6 hours later on days 1, 2, and 5 . The use of chlorhexidine achieved significantly (p less than 0.01) greater adjusted mean log10 bacterial count reductions than did povidone-iodine and chloroxylenol at all sampling times, with greater reductions as the study progressed. Monatsschr Kinderheilkd, 1988 Aug, 136(8), 475 - 8 {Antibiotic pharmacokinetics in patients with mucoviscidosis}; Gottschalk B et al.; In this review we summarize the available literature on the pharmacokinetics of antibacterials in cystic fibrosis . A special impact is given on the results of our group which will be put in perspective with the results of other authors . The homogeneity of our patient population allows a valid comparison between patient and volunteer data . We do not confirm the previously suggested strongly enhanced elimination of antibacterials in CF . Our findings have recently been confirmed by other investigators . However, since in the clinical situation a more heterogeneous group of patients is treated it seems rational to increase the dose of the antibacterials by about 20-30%. Antimicrob Agents Chemother, 1988 Aug, 32(8), 1119 - 23 Inhibition of Escherichia coli growth and diaminopimelic acid epimerase by 3-chlorodiaminopimelic acid; Baumann RJ et al.; The diaminopimelic acid (DAP) analog, 3-chloro-DAP, was synthesized and tested as the racemic acid for antibacterial activity and for inhibition of DAP epimerase . 3-Chloro-DAP was a potent inhibitor of DAP epimerase purified from Escherichia coli (Ki = 200 nM), and it is argued that 3-chloro-DAP is converted to a tight-binding transition state analog at the active site of this enzyme . Furthermore, 3-chloro-DAP inhibited growth of two E . coli mutants . In one of the mutants known for supersusceptibility to beta-lactams, inhibition was not seen until the mid-log phase of growth, while in the other mutant, a DAP auxotroph, inhibition occurred much earlier . Growth inhibition was reversed by DAP in both strains . In the auxotroph, the reversal was specific for meso-DAP, indicating that DAP epimerase was the target for 3-chloro-DAP . Thus we suggest a novel mechanism of bacterial growth inhibition which depends on DAP epimerase inhibition by a DAP analog. Clin Pharm, 1988 Aug, 7(8), 574 - 81 Mitoxantrone: a novel anthracycline derivative; Koeller J et al.; The chemistry, pharmacology, pharmacokinetics, clinical efficacy, dosage and administration, and adverse effects of mitoxantrone are reviewed . Mitoxantrone, an aminoanthraquinone that was synthesized in 1979, belongs to a new chemical class of agents known as the anthracenediones . It possesses antiviral, antibacterial, immunomodulatory, and antitumor activity . The drug's antitumor activity is attributed to its interaction with DNA topoisomerase II, and its interaction with human cells may also involve nonintercalary, electrostatic interactions . Mitoxantrone is poorly absorbed orally and is most commonly administered intravenously . The drug is rapidly distributed into the red blood cells, white blood cells, and platelets, followed by deep-tissue sequestration . Mitoxantrone has demonstrated clinical efficacy in the treatment of leukemia, lymphoma, and breast cancer . As a single agent, mitoxantrone has a response rate of roughly 30% in acute nonlymphocytic leukemia or acute myeloid leukemia . In combination with other standard agents (cytarabine, vincristine, and prednisone), the response rate may reach 60% . In breast cancer, mitoxantrone's response rate as a single agent is 25-30%, while combination regimens produce response rates of 60% or more . The drug can cause cardiotoxicity with cumulative doses . Other adverse effects include myelosuppression, nausea and vomiting, stomatitis, mucositis, and alopecia . The cost of mitoxantrone is comparable to that of doxorubicin, but it is substantially more expensive than daunorubicin . Mitoxantrone is an important new agent with antitumor activity in leukemia, lymphoma, and breast cancer . In most situations, mitoxantrone will be considered second-line treatment or a restricted-use item because of its high cost and because of the lack of FDA approval for indications other than acute nonlymphocytic leukemia. Antimicrob Agents Chemother, 1988 Aug, 32(8), 1182 - 6 Activity of fluoroquinolone antibiotics against Plasmodium falciparum in vitro; Divo AA et al.; The fluoroquinolone antibiotics are structurally related to nalidixic acid . Their primary antibacterial action appears to be mainly due to inhibition of DNA gyrase (DNA topoisomerase II) . We determined the activity of several fluoroquinolones in vitro against two strains of Plasmodium falciparum, FCC1 (chloroquine susceptible) and VNS (chloroquine resistant) . {3H}hypoxanthine incorporation by malarial parasites was determined at 48 and 96 h . The molarity at which each agent caused a 50% decrease in the incorporation of {3H}hypoxanthine compared with that of drug-free controls was defined as the 50% inhibitory concentration . The fluoroquinolones evaluated were amifloxacin, ciprofloxacin, enoxacin, norfloxacin, ofloxacin, and pefloxacin . Other DNA gyrase inhibitors tested were nalidixic acid, oxolinic acid, novobiocin, and coumermycin A1 . Among the fluoroquinolones, ciprofloxacin had the lowest 50% inhibitory concentrations at 48 h against both chloroquine-susceptible and -resistant strains of P . falciparum, (0.26 +/- 0.08) x 10(-4) and (0.38 +/- 0.15) x 10(-4) M, respectively (mean +/- standard deviation) . Enoxacin had the lowest 50% inhibitory concentrations against FCC1 and VNS at 96 h, 0.23 x 10(-5) and (0.06 +/- 0.04) x 10(-5) M, respectively . With the VNS strain, fractional inhibitory concentration indexes for the combination of ciprofloxacin and tetracycline were calculated at 48 and 96 h to be 0.93 and 0.79, respectively, indicating modest additive effects . The combination of novobiocin with ciprofloxacin showed indifference in the same system . The antimalarial effects of some fluoroquinolones occur at achievable serum concentrations . Whether inhibition of DNA gyrase contributes to the antimalarial activity of the fluoroquinolones is unknown at present. J Med Chem, 1988 Aug, 31(8), 1598 - 611 Design, synthesis, and properties of (4S)-7-(4-amino-2-substituted-pyrrolidin-1-yl)quinolone-3-carboxylic acids; Rosen T et al.; The quinolonecarboxylic acids constitute a class of extremely potent and orally active broad-spectrum antibacterial agents . These compounds have been shown to inhibit DNA gyrase, a key enzyme in bacterial DNA replication . The 7-(3-aminopyrrolidinyl)quinolone A-60969 (1) is a particularly potent member of this class and is currently undergoing clinical evaluation . We have studied a series of enantiomerically homogeneous (4S)-7-(4-amino-2-substituted-pyrrolidinyl)quinolones in an effort to utilize the 2-position of the pyrrolidine moiety to improve upon the solubility and pharmacokinetic properties of this class of compounds while still maintaining potent antibacterial activity . We have found that the absolute stereochemistry at the 2-position of the pyrrolidine ring is critical to the maintenance of such activity . In this paper, we report the full details of the asymmetric synthesis and the in vitro and in vivo structure-activity relationships of this series of compounds as well as the physiochemical properties, such as water solubility and log P, associated with the structural modifications . We also discuss the pharmacokinetic properties of several of these compounds in mice and the pharmacokinetics of 59, which has the best overall properties of agents in this study, in dog. J Antibiot (Tokyo), 1988 Jul, 41(7), 855 - 61 Boholmycin, a new aminoglycoside antibiotic . I . Production, isolation and properties; Saitoh K et al.; A novel aminoglycoside antibiotic, boholmycin, was produced by Streptomyces hygroscopicus H617-25 isolated from a soil sample collected in Bohol Island, the Philippines . It has a pseudotetrasaccharide structure composed of a heptose, two aminosugars and dicarbamoyl-scyllo-inositol . Intrinsic antibacterial activity of boholmycin is weak but it exhibits broad spectrum activity against Gram-positive and Gram-negative bacteria including aminoglycoside-resistant strains . Boholmycin is non-toxic in mice at 1,000 mg/kg intravenously. J Antibiot (Tokyo), 1988 Jul, 41(7), 892 - 8 Synthesis and beta-lactamase inhibitory activity of 9-(2-amidoethenylthio)-9-deoxy derivatives of clavulanic acid; Brooks G et al.; The reaction of activated derivatives of clavulanic acid with substituted amidoethenyl thiolates to give 9-(2-amidoethenylthio)-9-deoxy derivatives is described; the antibacterial/synergistic and beta-lactamase inhibitory activities of the thioethers and their corresponding sulfoxides and sulfones are compared. Fundam Appl Toxicol, 1988 Jul, 11(1), 120 - 31 Morphological investigation of osteochondrosis induced by ofloxacin in rats; Kato M et al.; Oral doses of 300 or 900 mg/kg/day of ofloxacin, a quinolone antibacterial agent, for 8 weeks induced a high incidence osteochondrotic lesions in rats . The predilection site of the lesions was the caudal area of the medial femoral condyle . Early changes included thickening of the middle zone of the articular cartilage with a markedly thinned deep zone . As the course of administration progressed, the columns of chondrocytes in the thickened middle zone became more and more numerous, many degenerated cells were seen, and the staining intensity of the matrix of the cartilage with with safranin-O decreased slightly . After the completion of dosing, the articular cartilage was markedly thickened and was made up mainly of middle zone cartilage . In advanced cases, a cleft was formed along the tidemark which occasionally extended to the articular surface . This resulted in erosion of the articular cartilage . Beneath the cleft there were focal necrosis of the subchondral bone and fibrotic lesions in the marrow space . Nalidixic acid also produced similar lesions in rats . The two drugs induced osteochondrosis in rats when treatment began at 4 weeks of age, but not at 8 weeks of age . This lesion was different in developmental process from the spontaneous osteochondrosis of rats, which is characterized by retention of the inherently thick deep zone. Fundam Appl Toxicol, 1988 Jul, 11(1), 110 - 9 Morphological investigation of cavity formation in articular cartilage induced by ofloxacin in rats; Kato M et al.; Ofloxacin, a quinolone antibacterial agent, induced blisters and/or erosions in the articular cartilage of the humeral trochlea, femoral condyle, and femoral head of immature rats . Histologically, cavity formation was seen in the middle zone of the articular cartilage . Changes were detected as early as 5 hr after a single oral administration of 1000 or 3000 mg/kg . These changes were characterized by condensation, atrophy, and deformation of the nuclei of chondrocytes distributed in the middle zone . In such nuclei, aggregation of heterochromatin was observed . Degenerated cells with vacuolated and partially disintegrated cytoplasms were also seen in this zone . These lesions were followed by edema of the matrix accompanied with markedly decreased stainability with safranin-O, and a cavity was formed later by liquefaction of the cartilage . The changes were reversible, with rebounding occurring even with continued treatment with ofloxacin . The proliferation of chondrocytes around the lesion chiefly contributed to the repair . Ofloxacin had no adverse effects on the articular cartilage in rats when treatment was initiated at 8 weeks of age or later. J Burn Care Rehabil, 1988 Jul-Aug, 9(4), 359 - 63 Combined topical use of silver sulfadiazine and antibiotics as a possible solution to bacterial resistance in burn wounds; Modak SM et al.; The superior efficacy of quinolones (norfloxacin, pefloxacin, and enoxacin) in controlling burn wound infections signals the discovery of new topical agents . However, there are a few reports on the emergence of resistant mutants to quinolones . Since attempts to develop AgSD resistant strains in vitro were unsuccessful and the emergence of AgSD resistance in vivo is a rare occurrence, we decided to investigate if the combined use of AgSD with other effective antibiotics, especially quinolones, would minimize the development of resistant bacteria . Our in vitro results indicate that when Ps . aeruginosa cultures were serially transferred 10 times through subinhibitory concentrations of norfloxacin, pefloxacin, etc., the MIC increased 40 times while when the cultures were passed through a combination of AgSD and these quinolones, the MIC of quinolones increased only tenfold . In vivo, when burned mice infected with either AgSD sensitive or resistant Ps . aeruginosa strains were treated with a topical cream containing 10mM silver sulfadiazine and 5mM norfloxacin or 5mM pefloxacin, the mortality was much lower than that of 10mM silver sulfadiazine alone or 5mM quinolones alone . Thus, combined use of silver sulfadiazine and quinolones appears to diminish the ability of Ps . aeruginosa strains to form resistant mutants . Furthermore, when the combination is used as a topical agent in burn wounds, lesser amounts of the individual drug are needed to control infection thereby reducing the toxic effects, if any, associated with these drugs . This combination does not in any way interfere with the antifungal or antibacterial properties of these individual drugs. Minerva Med, 1988 Jul, 79(7), 563 - 8 {A sulfadiazine-tetroxoprim combination (co-tetroxazine) in the treatment of the acute exacerbation of chronic bronchitis}; Gambaro MG et al.; After considering the bacterial flora which is most common in relapses in patients with bronchitis, 40 patients with chronic bronchitis have been treated with tetroxoprim a recently synthetized benzyl pyrimidine associated with sulfadiazine . One 350 mg tablet was administered every 12 hours for different periods, from 7 to 14 days . This study has shown how tetroxoprim has a wide antibacterial range, how it is well tolerated and extremely powerful in treating relapses of chronic infections in bronchi. J Hosp Infect, 1988 Jul, 12(1), 59 - 63 A comparison of two bactericidal handwashing agents containing chlorhexidine; Lee MG et al.; The skin disinfectant properties of two handwashing agents containing chlorhexidine, 'Uniscrub' and 'Hibiscrub', have been compared . The two products were assessed according to their ability to remove both transient organisms and natural or resident bacteria from the skin . They were found to be equally effective as antibacterial hand disinfection agents. Proc Natl Acad Sci U S A, 1988 Jul, 85(14), 5072 - 6 Channel-forming properties of cecropins and related model compounds incorporated into planar lipid membranes; Christensen B et al.; Cecropins, positively charged antibacterial peptides found in the cecropia moth, and synthetic peptide analogs form large time-variant and voltage-dependent ion channels in planar lipid membranes in the physiological range of concentration . Single-channel conductances of up to 2.5 nS (in 0.1 M NaCl) were observed, which suggests a channel diameter of 4 nm . Channels formed by the peptides cecropin AD and MP3 had a permeability ratio of Cl-/Na+ = 2:1 in 0.1 M NaCl . A comparative study of the three cecropins, cecropins A, B, and D, and of six synthetic analogs allowed determination of structural requirements for pore formation . Shorter amphipathic peptides did not form channels, although they adsorbed to the bilayer . A flexible segment between the N-terminal amphipathic region and the C-terminal more hydrophobic region of the peptide was required for the observation of a time-variant, voltage-dependent conductance . Cecropin AD was the most effective voltage-dependent pore-forming peptide and was also the most potent antibacterial peptide against several test organisms . A positive surface charge or cholesterol in the bilayer reduced the conductances caused by cecropin AD or MP3 by at least 5-fold . This behavior is consistent with the known insensitivity of eukaryotic cells to cecropins . Our observations suggest that the broad antibacterial activity of cecropins is due to formation of large pores in bacterial cell membranes. Acta Crystallogr C, 1988 Jun 15, 44 ( Pt 6), 1025 - 8 Structure of salicylaldehyde thiosemicarbazone; Chattopadhyay D et al.; C8H9N3OS, monoclinic, C2/c, a = 14.206 (3), b = 14.244 (4), c = 10.457 (4) A, beta = 116.18(2) degrees, V = 1898.9 (8) A3, Z = 8, Dm = 1.387, D chi = 1.366 g cm-3, lambda(Mo K alpha) = 0.71069 A, mu = 2.90 cm-1, F(000) = 816.0, T = 298 K, final R = 0.0429 for 1322 observed reflections . The S and hydrazinic N atoms lie trans . The lowering of antibacterial activity compared to that of 4-phenylthiosemicarbazide may be correlated with the decrease in negative charge on the hydrazinic N atom . The crystal structure is stabilized by hydrogen bonding, stacking interactions and van der Waals forces. Antibiot Khimioter, 1988 Jun, 33(6), 444 - 8 {Competition of antibacterial drugs for binding sites of human serum albumin}; Aver'eva EV et al.; Simultaneous binding of two drugs to human serum albumin (HSA) was studied by flow microcalorimetry . The following drug pairs were used: sulfadimethoxine and cefazolin . Sulfadimethoxine and dicloxacillin, sulfadimethoxine and chlortetracycline . A procedure for estimating the calorimetric titration curves in competing binding of the drugs to the HSA homogeneous active site is described . Comparison of the theoretical and experimental titration curves enabled detection of the ligand competition for the biopolymer binding site . It was shown that sulfadimethoxine displaced cefazolin in the HSA active site, the nature of the HSA association with dicloxacillin and sulfadimethoxine was independent and binding of doxycycline or chlortetracycline to HSA had no influence on sulfadimethoxine interaction with protein. J Antibiot (Tokyo), 1988 Jun, 41(6), 780 - 7 The synthesis of 2-(functionalized methyl)-1 beta-methylcarbapenems; Schmitt SM et al.; The synthesis of 1 beta-methylcarbapenems having a ROCH2 substituent at the 2-position is described . Their in vitro antibacterial activity and DHP-I susceptibilities are presented. J Antimicrob Chemother, 1988 Jun, 21 Suppl D, 113 - 9 Erythromycin acistrate and erythromycin stearate in the treatment of non-gonococcal urethritis; Rostila T et al.; The antibacterial efficacy and tolerability of erythromycin acistrate (EA) and erythromycin stearate (ES) were compared in 100 male patients with non-gonococcal urethritis (NGU) . The dosage of EA was 400 mg tid and that of ES 500 mg tid . Mean duration of treatment was ten days . When the final evaluation of the trial was made, the patient material was divided into two groups . One group consisted of patients with chlamydia-positive culture before treatment, the other of chlamydia-negative patients with signs of infection in the direct smear . There were 17 patients with chlamydial infection in the EA-group, and the microbiological cure rate was 100% . In the ES-group there were 21 patients with chlamydial infection and the microbiological cure rate was 95% . In the EA-group, the cure rate of chlamydia-negative NGU patients was 78%, and the corresponding figure in the ES-group was 86% . There was no difference in the cure rates between the two groups on either drug . In the EA-group, 25 patients (50%) reported side effects, in 22 these were gastrointestinal . In the ES-group, 26 patients (52%) reported side effects; in 22 these were gastrointestinal . Two patients in the EA-group discontinued the treatment because of gastrointestinal side effects . There were no differences between the groups in the frequency, severity and duration of side effects. J Med Chem, 1988 Jun, 31(6), 1227 - 30 The acylating potential of gamma-lactam antibacterials: base hydrolysis of bicyclic pyrazolidinones; Indelicato JM et al.; The acylating ability of the gamma-lactam ring of a new class of antibacterial agent, the bicyclic pyrazolidinones 1, was compared to that of the beta-lactam ring of clinically useful antibiotics by measuring chemical reactivity with hydroxide ion . The pyrazolidinone chemical reactivity spans the reactivity of classical beta-lactam antibiotics and the most reactive, 1i, is 13 times more reactive than the most reactive beta-lactam examined, ceftazidime . A correlation involving chemical reactivity, microbiological activity, and 3-substituent sigma p values was observed, and the correlation has led to the synthesis of new more potent bicyclic pyrazolidinones. Vestn Khir Im I I Grek, 1988 Jun, 140(6), 78 - 81 {Acute testicular diseases in children}; Sleptsov VP et al.; The work is based upon an experience with the treatment of 97 patients with acute diseases of the testicles aged from 6 months to 14 years . An analysis of remote results allows to recommend early urgent operative interventions which must be followed by complex antibacterial, desensitizing, antiinflammatory and immunodepressive therapy in the postoperative period. Vestn Khir Im I I Grek, 1988 Jun, 140(6), 35 - 8 {Obturator shunting in suppuration of vascular prostheses}; Zatevakhin II et al.; An experience with using obturatory shunts in 10 patients with suppurations of vascular prostheses after reconstructive operations on the aorto-iliac segment for its occlusive lesion is presented . The authors have come to a conclusion that extra-anatomical shunting through the closing inlet of the pelvis when combined with resection or removal of the infected vascular prosthesis, local and general antibacterial therapy is an effective method of treatment of the pathology in question . The modified method of shunting facilitates performing the operation in most critical patients . Good results were obtained in 7 of 10 patients operated upon . Two patients died . The amputation of the extremity was fulfilled in 1 patient. Vestn Khir Im I I Grek, 1988 Jun, 140(6), 13 - 7 {Diagnosis and treatment of acute abscesses of the lungs}; Lamm IaE et al.; Under study were results of clinical, immunological and bacteriological examinations of 130 patients with acute abscesses of the lungs . The complex treatment included antibacterial therapy taking into account the antibiotic sensitivity of the microflora, correction of disturbances of the protein and water-salt metabolism, desintoxication measures, immunotherapy and sanitation of purulent cavities and the tracheobronchial tree. Zentralbl Bakteriol Mikrobiol Hyg {A}, 1988 Jun, 268(4), 456 - 62 Antibacterial action of amphipathic derivatives of isoniazid against the Mycobacterium avium complex; Rastogi N et al.; The antibacterial action of amphipathic derivatives of isoniazid (INH) as compared to the parent hydrophilic molecule was determined against the bacteria of the Mycobacterium avium complex (MAC) using a 7H11 agar-dilution method . The results obtained showed a higher activity of 1-isonicotinyl-2-palmitoyl hydrazine and 1-isonicotinyl-2-(12 hydroxy dodecanoyl) hydrazine as compared to INH . However, when one mannose residue was terminally attached to the fatty acid chain of the latter, it lost its anti-MAC activity . 1-isonicotinyl-2-D-galacturonic acid hydrazone (but not hydrazine) also showed increased activity against MAC . Although pristinamycin was shown to bind to M . avium surface lipids, the INH-pristinamycin derivative was not more active than INH alone . These findings are discussed in respect to a proposed mechanism of diffusion across a lipid barrier. Farmaco {Sci}, 1988 Jun, 43(6), 559 - 66 Synthesis and in vitro antibacterial activity of a new series of monobactam derivatives; Valcavi U et al.; Using as a model monobactams with a substituted alpha-oxyimino moiety in the side chain (aztreonam), a series of 2-(2-aminothiazol-4-yl)-2-hydrazono-acetamido monobactam (II a, f) were prepared by condensation of the hydrazones (I a, e) (Z form) with tetrabutylammonium 3-amino-4-methyl-2-oxo-1-azetidin-sulphonate . Isomerization occurred during this synthesis and gave the E form of all compounds . Monobactams (II a, f) showed no significant in vitro antibacterial activity when compared with aztreonam and with some cephalosporins bearing the same E-hydrazono side chain. Farmaco {Sci}, 1988 Jun, 43(6), 501 - 5 Biological study of triterpenequinones from celastraceae; Gonzales AG et al.; The cytostatic activity of several triterpenequinone methides isolated from Rzedowskia tolantonguensis and Maytenus horrida (Celastraceae) was evaluated against HeLa cell cultures . Their ID50 were determined and compared with those of other related compounds . A preliminary study of the antibacterial activity of the above triterpenequinone methides was also carried out. J Vet Pharmacol Ther, 1988 Jun, 11(2), 191 - 6 The effect of various antibacterial preparations on the in vitro morphology and chemotactic response of equine neutrophils; Pycock JF et al.; Two independent assay systems were used to study the effect of three antibacterial preparations on in vitro morphology and chemotaxis of equine neutrophils . Incubation of neutrophils with high (200 micrograms/ml) and medium (20 micrograms/ml) concentrations of neomycin impaired their response to standard chemoattractants . Trimethoprim/sulfadoxine (0.4/2.0 micrograms/ml-40/200 micrograms/ml) and benzylpenicillin (0.25-25 micrograms/ml) had no effect . Neutrophils collected from geldings 2 and 24 h after neomycin (5 mg/kg) administration had impaired responses to standard chemoattractants . Benzylpenicillin (13.2 mg/kg) had no effect. J Pharmacobiodyn, 1988 Jun, 11(6), 386 - 94 Entry of the new quinolone antibacterial agents of ofloxacin and NY-198 into the central nervous system in rats; Sato H et al.; The present study describes quantitatively the pharmacokinetics of the antibacterial agents, ofloxacin and NY-198 (quinolonecarboxylic acid derivatives), in the central nervous system in rats by physiological modeling of the penetration, distribution and sequestration processes . The stimulation curves corresponded well with the observed concentrations in the cerebrospinal fluid (CSF) and various brain regions after intravenous bolus administration . The estimated cerebrovascular diffusion clearances were considerably small compared with reported serum flow rates and similar among the brain parenchymal tissues examined . The distribution volume of each drug in each brain region was almost the same as the brain extracellular space (15 to 25% of the wet weight) . It was also found that the Kp values of these drugs were similar among the various brain regions . These lines of evidence suggest that the antibacterial agents, ofloxacin and NY-198, localized only in the brain extracellular space and exhibited little region-specificity in distribution into the brain . Moreover, it was suggested from unexpectedly low CSF: serum concentration ratios after intravenous administration that these quinolones, which once diffused into CSF, could be sequestrated from CSF to blood via some transport system. Pathol Biol (Paris), 1988 Jun, 36(5 Pt 2), 647 - 50 {In vitro activity of 3 fluoroquinolones on Branhamella catarrhalis}; Suermondt G et al.; The in vitro antibacterial activities of three fluoroquinolones (pefloxacin, ofloxacin, ciprofloxacin) against 90 clinical isolates of Branhamella catarrhalis were assessed by determination of minimum inhibitory concentrations (MICs) . 73.5% of the strains were producing penicillinase . The MICS90 were as follow: ciprofloxacin = 0.2 mg/l . The MIC50 and the MIC90 were similar . There was no correlation of MICs with beta-lactam resistance . Lung parenchyma and bronchial mucus diffusion of these three fluoroquinolones allowed their utilisation in Branhamella catarrhalis bronchopulmonary infections. J Inorg Biochem, 1988 Jun, 33(2), 77 - 89 Synthesis of some 5-azo(4'-substituted benzene-sulphamoyl)-8-hydroxyquinolines with antidotal and antibacterial activities; Awad IM et al.; 5-Azo(4'-substituted benzenesulphamoyl)-8-hydroxyquinolines(III) have been prepared by coupling of the appropriate p-substituted benzenesulphamoyldiazonium acetates with 8-hydroxyquinoline . The corresponding copper chelates(IV) and iron chelates(V) were also prepared in a 1:2 metal to ligand ratio . Structures of III, IV and V were confirmed by some representative UV, IR, and NMR spectrometry in addition to microanalysis . Antidotal activity of four ligands (IIIa, IIId, IIIf, and IIIi) has been evaluated in mice against the toxicity of lead acetate and copper sulphate . Study revealed that compound IIIf elicited significant antidotal activity against lead and copper poisoning, while IIIi was potent only against lead poisoning . Antibacterial activity of compounds III, IV, and V was also determined in comparison to sulphanilamide against Staph . aureus, Bacill . cereus, and Esch . coli . The test compounds showed variable bacteriostatic activities, and some of them (IIIc, IIId, IIIf, Ve, IIIg, and Vi) are more effective than the reference drug, especially against Bacill . cereus. Patho