Antimicrobial

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.

Pathol Biol (Paris), 1988 Jun, 36(6), 795 - 800
{Habekacin: a new aminoglycoside . Study of nephrotoxicity in rats in comparison with gentamicin, netilmicin and amikacin}; Olier B et al.; Habekacin is a new aminoglycoside antibiotic . In this study we want to know the effect of increasing dose of habekacin on renal function and on renal morphology . We decide to compare the renal alterations induced by habekacin to these provoked by gentamicin, netilmicin and amikacin . Female Wistar rats received intraperitonally a single injection daily of 10, 30, 50, 150 mg/kg of habekacin for seven days . Wistar rats received also 50 mg/kg gentamicin, 50 mg/kg netilmicin and 150 mg/kg amikacin . No mortality was observed in groups treated with 10, 30, 50 mg/kg habekacin but 50 per cent of rats died with 150 mg/kg habekacin . Habekacin--30 mg/kg seven days--induced a decrease of cortical enzymatic activities, an increase of the number of lysosomes, a great accumulation of myeloid bodies, an alteration of lysosomal membranes Habekacin--50 mg/kg seven days and 150 mg/kg--induced a decrease of creatinine clearance and ultrastructural alterations of renal tubular cells . Comparative studies with other aminoglycosides showed that amikacin--150 mg/kg was the lesser nephrotoxic drug . With a same dose of 50 mg/kg, gentamicin appeared lesser nephrotoxic than habekacin and habekacin seemed to induce a same degree of renal modifications than netilmicin . With the dose of 150 mg/kg habekacin this drug was higher nephrotoxic than 50 mg/kg gentamicin . In conclusion, if it could be necessary to use habekacin and to prefer this aminoglycoside to gentamicin from an antibacterial activity point of view it is necessary to keep in mind that this drug is potentially nephrotoxic and that the dosage had to be strictly respected.(ABSTRACT TRUNCATED AT 250 WORDS)

Pathol Biol (Paris), 1988 Jun, 36(5 Pt 2), 711 - 4
{Interaction of roxithromycin with human polymorphonuclear neutrophils in vitro and ex vivo}; Labro MT et al.; Roxithromycin (RU 28965) a new semisynthetic macrolide has been reported to display an antibacterial spectrum and activity in vitro similar to those of others macrolides . However, roxithromycin seems more efficient than erythromycin in in vivo experimental infections (mice) . We have previously reported that roxithromycin increases the ability of human neutrophils (PMN) for bactericidal activity (S . aureus) or phagocytosis (K . pneumoniae) in vitro without altering other PMN functional parameters . In this study, roxithromycin (single dose-300 mg) was given to 6 human volunteers . The neutrophils collected 90 min after ingestion display a significant increased ability to phagocytose and kill S . aureus and K . pneumoniae . Furthermore chemotaxis, oxidative burst and myeloperoxidase activity of the PMN after roxithromycin ingestion were enhanced compared to those of PMN before ingestion . This discrepancy between immunomodulating effect of roxithromycin in vitro and in vivo outlines the complexity of in vivo experimental models and requires further studies in vivo in particular in patients suffering from sepsis.

Antimicrob Agents Chemother, 1988 Jun, 32(6), 925 - 7
Antibacterial characteristics of YTR 830, a sulfone beta-lactamase inhibitor, compared with those of clavulanic acid and sulbactam; Moosdeen F et al.; The antibacterial activity, binding to penicillin-binding proteins, and morphological changes effected by YTR 830, a sulfone beta-lactamase inhibitor, were studied in comparison with those of other beta-lactamase inhibitors . YTR 830 had very poor antibacterial activity, bound to PBP 2 of gram-negative organisms, and at the MIC caused rapid lysis of spheroplasts formed.

Acta Crystallogr C, 1988 May 15, 44 ( Pt 5), 900 - 2
Polymorph IV of 4-amino-N-2-pyridinylbenzenesulfonamide (sulfapyridine); Bernstein J; C11H11N3O2S, Mr = 249.3, monoclinic, P2(1)/c, a = 13.56 (4), b = 6.48 (1), c = 14.12 (3) A, beta = 113.7 (1) degrees, V = 1136.4 (44) A3, Z = 4, D chi = 1.457 g cm-3, lambda(Mo K alpha) = 0.70926 A, mu = 2.29 cm-1, F(000) = 520, T = 291 K, final R = 0.085 for 1287 independent observed reflections . Sulfapyridine is a sulfonamide drug with antibacterial, antithyroid and antidiabetic properties . The molecule exhibits the same conformation as in all except one of the polymorphs previously studied, despite a hydrogen-bonded packing mode which differs from that observed in the three earlier reported polymorphs . Form IV exhibits three hydrogen bonds of the type N...N = 2.91 (1) A and N...O = 3.007 (7) and 3.076 (7) A.

J Antibiot (Tokyo), 1988 May, 41(5), 614 - 23
Chemical modification of hitachimycin . Synthesis, antibacterial, cytocidal and in vivo antitumor activities of hitachimycin derivatives; Shibata K et al.; Several acyl derivatives of hitachimycin have been synthesized and their activities, including antibacterial, cytocidal against HeLa cells and in vivo antitumor against sarcoma 180, evaluated . Some of these derivatives showed higher antitumor activity than hitachimycin . Among the derivatives, 11-O-propionyl-15-O-butyrylhitachimycin (12) and the 11-O-acylhitachimycins (15-17) were most effective in in vivo assay.

J Med Chem, 1988 May, 31(5), 983 - 91
Quinolone antibacterial agents . Synthesis and structure-activity relationships of 8-substituted quinoline-3-carboxylic acids and 1,8-naphthyridine-3-carboxylic acids; Sanchez JP et al.; A series of 7,8-disubstituted 1-cyclopropyl-6-fluoroquinoline-3-carboxylic acids, 7-substituted 1-cyclopropyl-6-fluoro-1,8-naphthyridine-3-carboxylic acids, and 10-substituted 9-fluoropyridobenzoxazine-6-carboxylic acids has been prepared and evaluated for antibacterial activity . The side chains examined at the 7-position (benzoxazine 10-position) included piperazinyl (g), 3-aminopyrrolidinyl (a), 3-(aminomethyl)pyrrolidinyl (b), and alkylated 3-(aminomethyl)pyrrolidinyl (c-f) . Variations at C-8 of the quinolone ring system included hydrogen, nitro, amino, fluorine, and chlorine . The relative enhancement of in vitro activities by the side chains on the 8-hydrogen quinolone and 1,8-naphthyridine against Gram-negative organisms was a greater than b greater than g greater than c-f . The activity imparted to the substituted quinolone nucleus by the 8-substituent was in the order F greater than Cl greater than naphthyridine greater than H greater than benzoxazine greater than NH2 greater than NO2 . These trends were retained in vivo.

Med Clin North Am, 1988 May, 72(3), 567 - 79
Imipenem: a new carbapenem antibiotic; Lipman B et al.; Imipenem is a new carbapenem antibiotic that has an extremely broad spectrum of antibacterial activity . It has been used to treat a variety of serious infections and an increasing volume of literature documents its value in infections due to multiresistant bacteria . This article reviews the antibacterial activity, pharmacology, and clinical uses of imipenem.

J Pharm Sci, 1988 May, 77(5), 458 - 60
Synthesis and antibacterial activity of 6-difluoromethoxy-7-piperazinyl-3-quinolinecarboxylic acid derivatives; Krishnan R et al.; A series of novel 3-quinolinecarboxylic acid derivatives has been prepared and their antibacterial activity evaluated . These derivatives were characterized by a difluoromethoxy group attached to the 6-position and substituted piperazinyl groups attached to the 7-position.

Pathol Biol (Paris), 1988 May, 36(5), 357 - 60
{In vitro antibacterial activity of piperacillin/quinolone combinations}; Soussy CJ et al.; Combinations of piperacillin (PIP) with 3 systemic fluoroquinolones: pefloxacin (PEF), ofloxacin (OFL) and ciprofloxacin (CIP) were evaluated by checkerboard technique (bacteriostatic activity) and by time-killing curve technique (bactericidal activity as a function of time) for 4 bacterial strains with following MICs (micrograms/ml): 1 E . coli (PIP: 1, PEF: 0.12, OFL: 0.06, CIP: 0.016); 1 S . marcescens (0.25, 0.06, 0.06, 0.016); 2 P . aeruginosa (2, 1, 0.5, 0.12 and 4, 2, 2, 0.25) . Bacteriostatic activity of the 3 combinations showed only different or additive effects (index FIC: 0.62 to 1.5) . If the bactericidal activity was defined as a less than or equal to 3 log 10 decrease in CFU/ml in 3-6 h and less than or equal to 4 log 10 in 6-24 h, PIP was not bactericidal at MIC x 8 for all strains; nevertheless, combinations of PIP 2 + PEF 0.25, OFL 0.12 or CIP 0.016 on E . coli and PIP 1 + PEF 0.25, OFL 0.25 or CIP 0.06 on S . marcescens showed bactericidal activity, superior to each antibiotic singly . For P . aeruginosa a less than or equal to 4 log 10 decrease in 6-24 h was observed only in combination with PIP 16 + PEF 1, OFL 1 or CIP 0.25 and PIP 32 + PEF 4, OFL 4 or CIP 0.5 . Combinations of PIP with quinolones showed synergistic effects: bactericidal activity was more rapid and prolonged with such combinations at concentrations near MICs and obtained with usual therapeutic doses.

Clin Chem, 1988 May, 34(5), 920 - 4
Effect of blood collection and processing on radioimmunoassay results for apolipoprotein A-I in plasma; Brown SA et al.; We studied the effects of different procedures of blood collection and processing on quantification of apolipoprotein A-I (apoA-I) by radioimmunoassay . ApoA-II and apolipoproteins of low- and very-low-density lipoproteins did not cross react in the assay . Analytical recovery of apoA-I at different doses was complete . ApoA-I concentration in pooled human plasma was stable for as long as a year stored at -70 degrees C . Inter- and intra-assay CVs averaged 7% and 5%, respectively . We collected blood from 20 subjects into tubes containing EDTA alone or EDTA with antiproteolytic agents, then separated the plasma either immediately or after 3 h at 4 degrees C . We tested various formulations of antibacterial, antiproteolytic, and anti-oxidant agents added to plasma, measuring apoA-I concentrations either within 24 h of blood collection or after storage of plasma for 6 weeks at -70 degrees C . No significant difference in the concentrations of apoA-I was found in these specimens, regardless of the conditions studied . We conclude that addition of protective agents other than EDTA is not necessary during blood collection or specimen processing for reliable quantification of apoA-I in fresh or frozen human plasma.

J Burn Care Rehabil, 1988 May-Jun, 9(3), 253 - 7
The role of topical treatment as a determinant of infection in outpatient burns; Heinrich JJ et al.; Up to 95% of all burned patients are treated as outpatients . While uniform guidelines exist to evaluate the severity of an outpatient's burn, treatment forms vary greatly . Furthermore, the relative merits of one treatment modality over another have not been demonstrated . This study reviews 262 patients with uncomplicated, thermal partial-thickness burns . All of these patients were treated with either a petrolatum fine-mesh gauze (FMG = 102), a topical penetrating antibacterial agent (TPA = 58), or a topical nonpenetrating antibacterial agent (TNA = 102) . The size of the injury along with its location and etiology, the age of the patient, the time from injury to treatment, and comorbid factors were comparable among the major treatment groups . On follow-up, a wound was classified as infected if it exhibited erythema, tenderness, increased warmth, and edema (cellulitis) . Infection rates were 2.0% (2/102) in the FMG group, 5.2% (3/58) in the TPA group, and 2.0% (2/102) in the TNA group . The differences among the rates did not reach statistical significance (P = 0.41) . Given the cost of treatment, frequency of dressing changes and overall patient comfort, we advocate FMG as the optimal method for the care of uncomplicated partial-thickness outpatient burns.

J Inorg Biochem, 1988 May, 33(1), 57 - 65
Ligational behavior of two biologically active N-S donors toward oxovanadium(IV) ion and potentiation of their antibacterial activities by chelation to metal ions . Part III; Maiti A et al.; Chelating behavior of two biologically active ligands, pyridine-2-carboxaldehyde thiosemicarbazone (PT) and pyridine-2-carboxaldehyde-(4-phenyl)thiosemicarbazone (PPT), toward oxovanadium(IV) ion has been studied . The ligands are found to react in the thioketo form (pH 2-4), yielding the complexes {VO(PT)X2}(X = Cl-, Br-, ClO4-), {VO(PT)(SO4)H2O}, {VO(PPT)2X}X (X = Cl-, Br-, ClO4-) and {VO(PPT)2SO4} . Reactions of {VO(PT)(SO4)H2O} and {VO(PPT)2X}X (X = Cl-, Br-, ClO4-) with a monodenate Lewis base (B) like pyridine lead to the formation of {VO(PT)(SO4)Py}H2O and {VO(PPT)2py}X2 respectively . Bonding sites of the donor molecules around the oxometal cation have been located . Nature of the EPR spectra and magnetic moment values point to the monomeric character of the complexes and suggest a distorted octahedral donor environment for the oxovanadium(IV) ion . Status of the metal-oxygen multiple bond in all the complexes has been computed in terms of the V-O(1) stretching force constant . The ligands themselves and most of their oxovanadium(IV) complexes are found to exert powerful in vitro antibacterial activities towards E . coli.

J Med Chem, 1988 May, 31(5), 991 - 1001
1-Substituted 7-{3-{(ethylamino)methyl}-1-pyrrolidinyl}-6,8- difluoro-1,4-dihydro-4-oxo-3-quinolinecarboxylic acids . New quantitative structure-activity relationships at N1 for the quinolone antibacterials; Domagala JM et al.; A series of 18 1-substituted 7-{3-{(ethylamino)methyl}-1- pyrrolidinyl}-6,8-difluoro-1,4-dihydro-4-oxo-3-quinoline- carboxylic acids (N1 analogues of CI-934) were synthesized and evaluated for antibacterial activity and DNA-gyrase inhibition . Correlations between the inhibition of DNA gyrase and antibacterial potency were established . A quantitative structure-activity relationship (QSAR) was derived by using the antibacterial potency for each of 11 strains of bacteria and the Gram-negative mean . The equations indicated that antibacterial potency was strongly dependent on STERIMOL length and width and the level of unsaturation of the N1 substituent . Some strains also showed a dependence on the presence of heteroatoms (O, N, S) in the N1 group . No significant correlations between gyrase inhibition and combinations of these parameters were found . These QSAR results are discussed in conjunction with the conformational analyses from molecular modeling studies . The substituent that most enhanced the activity of the quinolone in all regards was the cyclopropyl group . This analogue, 1-cyclopropyl-7-{3-{(ethylamino)-methyl}-1-pyrrolidinyl}-6, 8-difluoro-1,4-dihydro-4-oxo-3-quinolinecarboxylic acid (PD 117558), demonstrated outstanding broad spectrum activity both in vitro and in vivo when compared to relevant standards.

FEBS Lett, 1988 Apr 25, 231(2), 299 - 302
Effects on electrophoretic mobility and antibacterial spectrum of removal of two residues from synthetic sarcotoxin IA and addition of the same residues to cecropin B; Li ZQ et al.; Cecropin B and cecropin IA (sarcotoxin IA) are 35- and 39-residue antibacterial peptides from a silk moth and a meat fly, respectively . Using solid phase synthesis we have made these peptides as well as two 37-residue analogs, one containing a deletion of leucine and lysine (residues 2a and 2b) as compared to cecropin IA, the other containing an insertion of leucine and lysine at the corresponding place in cecropin B . This addition and removal of a lysine residue did not cause the expected change in electrophoretic mobility . When tested for antibacterial spectra, the insertion analog was found to be as active as the parent compound while the deletion analog had lost most of its antibacterial capacity . In addition it was shown that the C-terminal amide contributes to the broad spectrum properties of the cecropins.

J Immunol Methods, 1988 Apr 22, 109(1), 17 - 25
A safe and efficient method for elimination of cell culture mycoplasmas using ciprofloxacin; Schmitt K et al.; The antibacterial activity of ciprofloxacin, a 4-fluoroquinolone antibiotic, in the control of mycoplasma contamination in experimentally infected cell lines has been investigated . Seven mycoplasma species, including M . hyorhinis, M . gallisepticum, M . orale, M . salivarium, M . hominis, M . fermentans, and M . arginini, which had chronically infected the murine plasmocytoma line X63-Ag8 653, were eradicated with 10 micrograms/ml ciprofloxacin . Wild type laboratory infections of two human cell lines, HL-60 and U-937, were eliminated by 12 days of such treatment . Mycoplasma decontamination of cell cultures was monitored by the cultivation method 4 weeks after treatment . No side effects were seen in cell cultures and complex proliferation assays with cells of human and murine origin, using ciprofloxacin in doses up to 2.5 times the usual bactericidal concentration.

Wien Med Wochenschr, 1988 Apr 15, 138(6-7), 147 - 50
{Preventive use of antibacterials with a single administration of 1 g ceftriaxone in gynecology and obstetrics}; Hrgovic Z et al.; An indication for prophylaxis in vaginal and abdominal hysterectomy is given in the case of high postoperative infection morbidity . In order to reach an adequate level of antibacterial activity in serum and tissue one should apply the initial dose before the operation . The presence of various risk factors in Caesarean section is also an indication for prophylaxis . This applies especially to emergency Caesarean sections which have an increased infection rate . The application of the substance should follow the separation of the child from the mother after cutting the umbilical cord in order to prevent a diaplacental diffusion of the substance which can lead to a false diagnosis of the newborn . Our clinical studies demonstrated that an infection prophylaxis in gynaecological obstetrical standard operations is very effective with a single application of 1 g Ceftriaxone . Only 1 from 90 patients developed a postoperative infection . There were only 2 patients with side effects, which were diarrhoea and an allergical reaction . The hematological, hepatical and nephrological function tests did not indicate any alteration of values related to the test substance . Finally we have observed that Ceftriaxone has not only proven to be highly effective in a perioperative antibiotic prophylaxis in extensive gynaccological and obstertrical operations, but also a compatible medicament in view of the rare occurrence of side effects . The clinical application of this medicament in gynaecology and obstetrics can therefore be recommended.

Biochim Biophys Acta, 1988 Apr 7, 939(2), 260 - 6
Binding and action of cecropin and cecropin analogues: antibacterial peptides from insects; Steiner H et al.; The mechanism of action of cecropin was studied by using liposomes as a model system . The bilayer was efficiently destroyed if the liposome net charge was zero or negative . Cecropin analogues with an impaired N-terminal helix had reduced membrane disrupting abilities that correlate with their lower antibacterial activity . The reduced bactericidal activity of the analogues was rationalized in terms of reduced binding to bacteria . The stoichiometry of cecropin killing of bacteria suggests that amounts of cecropin sufficient to form a monolayer strongly modify the bacterial membrane . Although some bacteria were resistant to cecropin they did bind large amounts in a non-productive manner . In contrast, mammalian erythrocytes achieve resistance by avoiding the binding of cecropin.

Allergy, 1988 Apr, 43(3), 184 - 91
Drugs as allergens . The molecular basis of IgE binding to trimethoprim; Smal MA et al.; The combining site specificities of IgE antibodies that react with the oral antibacterial agent trimethoprim and found in the sera of two subjects who experienced anaphylaxis after taking the drug, were investigated . Hapten inhibition studies with some close analogues of trimethoprim and a range of other structurally related compounds showed that the allergenic determinant complementary to the IgE antibodies in the serum of one of the subjects was the 3,4-dimethoxybenzyl group . The complementary allergenic structure recognized by the IgE antibodies in the serum from the second subject comprised both the trimethoxybenzyl and diaminopyrimidine rings of trimethoprim . Thus, as with thiopentone, but unlike the neuromuscular blocking drugs, the trimethoprim molecule has more than one determinant each with the capacity to provoke IgE formation, interact with the antibody combining site and provoke drug-induced allergic reactions . The general approach set out here employing carefully selected structural analogues in hapten inhibition studies should be invaluable for confirming specificity and identifying allergenic determinants in IgE antibody-mediated allergic drug reactions.

J Am Acad Dermatol, 1988 Apr, 18(4 Pt 1), 714 - 20
Aloe vera; Klein AD et al.; We review the scientific literature regarding the aloe vera plant and its products . Aloe vera is known to contain several pharmacologically active ingredients, including a carboxypeptidase that inactivates bradykinin in vitro, salicylates, and a substance(s) that inhibits thromboxane formation in vivo . Scientific studies exist that support an antibacterial and antifungal effect for substance(s) in aloe vera . Studies and case reports provide support for the use of aloe vera in the treatment of radiation ulcers and stasis ulcers in man and burn and frostbite injuries in animals . The evidence for a potential beneficial effect associated with the use of aloe vera is sufficient to warrant the design and implementation of well-controlled clinical trials.

Ann Rheum Dis, 1988 Apr, 47(4), 323 - 7
Co-trimoxazole in rheumatoid arthritis: a comparison with sulphapyridine; Astbury C et al.; The antirheumatoid activity of sulphasalazine and sulphapyridine may result from their antibacterial properties . The second line activity of sulphamethoxazole, in the form of cotrimoxazole (CTZ), has been investigated by treatment of 13 patients with RA for 24 weeks with CTZ (480 mg three times a day) . The drug was found to be poorly tolerated, only five of the thirteen patients recruited completing the study . High circulating concentrations of sulphamethoxazole were found, with mean (SD) steady state serum concentrations reaching 54.02 (23.38) micrograms/ml . A significant reduction in serum IgM from 280 to 130 IU/l was observed, but otherwise disease activity remained unchanged or deteriorated throughout the course of the study . In contrast, patients with RA treated with sulphapyridine (1.25 g a day) showed improvement in disease activity . The results argue against an antibacterial mechanism of action for sulphasalazine and sulphapyridine in rheumatoid arthritis, unless this occurs at a site inaccessible to sulphamethoxazole.

Microbiologica, 1988 Apr, 11(2), 137 - 42
Comparative in vitro activity of imipenem against gram-positive and gram-negative aerobic bacteria from clinical isolates; Bastianini L et al.; Imipenem is a member of a new class of beta-lactam antibiotics, carbapenems, with a very broad antibacterial spectrum . In this work we evaluated the in vitro activity of imipenem against a variety of bacterial strains isolated from clinical specimens as well as the activity of other beta-lactam antibiotics . The results obtained with 501 bacterial strains show that imipenem is active on both gram-negative and gram-positive microorganisms isolated from different infections . The in vitro inhibitory activity is greater than that of aztreonam, cefotaxime, ceftriaxone, piperacillin, amikacin, and netilmicin, against the majority of strains tested.

Burns Incl Therm Inj, 1988 Apr, 14(2), 91 - 100
Comparison of standard and chlorhexidine-derivative topical antibacterial agents on the infected burned rat wound; Snelling CF et al.; The effect of daily treatment with three current topical antibacterial agents and four experimental formulations of chlorhexidine was evaluated after 1 week in rats with full thickness burns . The burn was seeded with 1 x 10(8) colony forming units (CFU) of a strain of P . aeruginosa isolated from the infected wound of a burn patient . Mafenide acetate resulted in the lowest incidence of muscle invasion and yielded the lowest mean eschar and muscle concentrations . Mafenide acetate, gentamicin, and chlorhexidine diphosphanilate (0.5 per cent) had lower mean eschar and muscle concentrations than silver sulphadiazine 1 per cent alone . Addition of chlorhexidine digluconate (0.5 per cent or 1.0 per cent) to silver sulphadiazine reduced mean eschar concentrations but not muscle concentrations compared to silver sulphadiazine alone . All treatments effectively suppressed systemic invasion of lung and blood and prevented death compared with controls . Mafenide acetate, gentamicin sulphate and chlorhexidine disphosphanilate 0.5 per cent were most effective against this patient strain of P . aeruginosa.

J Biochem (Tokyo), 1988 Apr, 103(4), 735 - 9
Inhibitory effect of sarcotoxin IIA, an antibacterial protein of Sarcophaga peregrina, on growth of Escherichia coli; Ando K et al.; The effect of sarcotoxin IIA, an antibacterial protein of Sarcophaga peregrina (flesh fly), on Escherichia coli was investigated . Sarcotoxin IIA was found to have a bacterial effect on growing bacteria, but little on non-growing bacteria . At a concentration of 25 micrograms/ml, it induced significant morphological change of growing E . coli cells . In its presence, growing cells became greatly elongated, and spheroplast-like bulges and projections appeared on their surface . A rough mutant strain of E . coli with a defect in the structure of lipopolysaccharide was more sensitive than the parent strain to sarcotoxin IIA . These results suggest that the main effect of sarcotoxin IIA is to inhibit cell wall synthesis, including septum formation.

Jpn J Antibiot, 1988 Apr, 41(4), 427 - 36
{A study on the bactericidal action of aspoxicillin against Escherichia coli}; Nakanishi N et al.; In an attempt to clarify the role of a side chain, N4-methyl-D-asparagine, of aspoxicillin (ASPC) in the antibacterial action, we examined the bactericidal activity of dehydroxyaspoxicillin (AB-ASPC) and its affinity for the penicillin-binding proteins (PBPs) of Escherichia coli using piperacillin (PIPC), mezlocillin (MZPC) and apalcillin (APPC) as the reference penicillins . ASPC and AB-ASPC showed high bactericidal activities against E . coli K-12 even when a large inoculum size (2 x 10(8) CFU/ml) was used . The observation of these cultures with a phase contrast microscope revealed that E . coli cells lysed after the formation of spheroplast-like or bulged structures . On the other hand, PIPC, MZPC and APPC converted the cells to long filaments, but did not show lytic action in the range of the concentrations used . These morphological changes were also observed with a scanning electron microscope . Superior bacteriolytic activities of ASPC and AB-ASPC were further shown by measuring 'triggering' autolytic activity by the penicillins . The release of labeled murein from E . coli chi 1776 after the exposure to ASPC or AB-ASPC was clearly greater than those caused by the reference penicillins . ASPC showed affinity for PBPs of E . coli K-12, 1A, 1Bs, 2 and 3, and its affinity pattern resembled the one obtained with ampicillin (ABPC) . AB-ASPC behaved in a fashion similar to ASPC, although its affinities for PBP 1A and 1Bs were lower and that for PBP 3 was slightly higher . These observations suggest that the highest bactericidal activity of ASPC against E . coli with lysis among the acyl-ureidopenicillins tested is due to N4-methyl-D-asparagine in the side chain of ASPC.

Biochim Biophys Acta, 1988 Mar 31, 949(3), 279 - 87
Studies on the interaction of 4-quinolones with DNA by DNA unwinding experiments; Tornaletti S et al.; It has been recently found that, contrary to prior belief, norfloxacin, a member of the 4-quinolone family of antibacterial drugs that specifically inhibit DNA gyrase, does not bind to the enzyme but instead to DNA . We have performed DNA unwinding experiments in order to decide whether binding of norfloxacin to DNA introduces changes in its supercoiled conformation . We have found that: (i) norfloxacin and nalidixic acid are capable of unwinding the double helix, thus confirming the binding of these antibiotics to DNA; (ii) DNA unwinding can be observed only in the presence of Mg2+ and decreases with increasing KCl concentration; (iii) the extent of unwinding varies in different DNA molecules, suggesting a sequence preference of norfloxacin binding to DNA.

Biochemistry, 1988 Mar 8, 27(5), 1715 - 21
Molecular cloning, sequencing, and characterization of cDNA for sarcotoxin IIA, an inducible antibacterial protein of Sarcophaga peregrina (flesh fly); Ando K et al.; A cDNA clone for sarcotoxin IIA, an antibacterial protein of Sarcophaga peregrina (flesh fly) larvae {Ando, K., Okada, M., & Natori, S . (1987) Biochemistry 26, 226-230}, was isolated and characterized . Sarcotoxin IIA was found to consist of 270 amino acid residues . Northern blot analysis showed that the sarcotoxin IIA gene was activated in response to injury of the body wall of the larvae . The gene was activated for much longer after injection of Escherichia coli into the abdominal cavity of larvae than after injection of saline alone . A common nucleotide sequence for mammalian inflammatory mediator protein cDNAs, TTATTTAT, was found in the 3'-untranslated region of sarcotoxin IIA cDNA, suggesting that this protein plays a role in the inflammatory response of this insect.

J Theor Biol, 1988 Mar 7, 131(1), 115 - 34
Kinetics of drug activities as influenced by their physico-chemical properties: antibacterial effects of alkylating 2-furylethylenes; Balaz S et al.; A method is presented allowing for direct incorporation of the time of exposure into the relationship between biological and physico-chemical properties of drugs . The approach employs kinetics of the drug-receptor interaction based on mass action law, whereby biological response is considered as proportional to the receptor modification, and the time-dependent drug concentration in the vicinity of receptors is expressed by a disposition function . The function with variable physico-chemical properties and time relates the intracellular drug concentration to the dose . General description of individual steps in the development of a quantitative structure-time-activity relationship (QSTAR) is illustrated in detail using the data on antibacterial effects of alkylating 2-furylethylenes . It is shown that common approaches to description of quantitative structure-activity relationships (QSAR), working with a prefixed time of exposure, represent special cases of the method presented and can even be improved using its conclusions.

J Antibiot (Tokyo), 1988 Mar, 41(3), 332 - 42
cis-Halovinylthioacetamido side chain, a new effective structural element for 7 beta-substitution in cephem and oxacephem antibiotics . II . 7 beta-cis-Fluorovinylthioacetamino-7 alpha-methoxy-1-oxacephems; Nishitani Y et al.; The synthesis and in vitro activity of 1-oxacephem derivatives having a substituted or a non-substituted cis-fluorovinylthioacetamido side chain at C-7 are described . Of these new 1-oxacephem antibiotics, 2355-S (42a) shows good antibacterial activity against Gram-positive and Gram-negative bacteria, and very favorable pharmacokinetic properties.

J Hand Surg {Am}, 1988 Mar, 13(2), 254 - 9
A protocol for the treatment of severe infections of the hand; Spiegel JD et al.; A protocol for the treatment of hand infections was used for 69 patients in a university teaching hospital . The protocol prescribes incision and drainage under optimal conditions (in the operating room) when the patient is first seen and intravenous antibacterial therapy effective against anaerobic and aerobic bacteria initiated immediately after obtaining aerobic and anaerobic cultures . Results of bacteria studies confirmed the significant frequency (nearly 30%) of mixed aerobic and anaerobic infection . Use of the protocol resulted in a shorter hospital stay, faster healing, and fewer complications (recrudescence of infection, reoperation, stiffness, arthritis, and osteomyelitis) when compared with 107 patients who were treated before institution of the protocol.

J Reprod Fertil, 1988 Mar, 82(2), 875 - 92
The functions of uterine secretions; Roberts RM et al.; The likely functions of uterine secretions, often termed histotroph, in the nurture of the early conceptus are reviewed . Particular emphasis has been placed on the pig in which the uterus synthesizes and secretes large amounts of protein in response to progesterone . In this species, which possesses a non-invasive, diffuse type of epitheliochorial placentation, the secretions provide a sustained embryotrophic environment which is distinct from that of serum . A group of basic proteins dominates these uterine secretions after Day 11 of pregnancy and its best characterized member is uteroferrin, an iron-containing acid phosphatase with a deep purple colour . Evidence has accumulated to suggest that uteroferrin, rather than functioning as an acid phosphatase, is involved in transporting iron to the conceptus . Three basic polypeptides which are found noncovalently associated with uteroferrin have been shown to be antigenically closely related to one another and to have arisen by post-translational processing from a common precursor molecule . Their function is unknown . A group of basic protease inhibitors has been identified which bear considerable sequence homology to bovine pancreatic trypsin inhibitor (aprotinin) and may control intrauterine proteolytic events initiated by the conceptuses . The last basic protein so far characterized is lysozyme which is presumed to have an antibacterial role . Finally, two low molecular weight (Mr approximately 18,000) acidic polypeptides have been purified and have sequence homology to a plasma retinol binding protein . Like uteroferrin, these proteins may be responsible for transport of an essential nutrient to the conceptus.

Tijdschr Diergeneeskd, 1988 Mar 1, 113(5), 254 - 9
{The New Dutch Kidney Test . III . Practical evaluation}; Broex NJ et al.; The New Netherlands Kidney Test (NNKT) is a method used to detect residues of antibacterial agents in slaughtered animals . This test will shortly be substituted for the current Netherlands Kidney Test (NKT) . The new method was tested for its suitability in meat inspection in the field by four district laboratories, comparative studies with the current Netherlands Kidney test being done at the same time . These investigations showed that, when the new test (NNKT) was used, 5.3 per cent of the category of diseased animals and, using the current Netherlands Kidney Test, 2.2 per cent of these animals were positive . When control discs were used, it was shown that reproducibility of the new test (NNKT) within and between the participating laboratories was satisfactory . A method was developed to obtain similar results on re-examination with the NNKT as those obtained in the first inspection . By freezing the duplicate discs at the time of performance of the test and using these discs for re-inspection, reproducible results were obtained with the NNKT . The substance inhibiting the growth of bacteria was identified in a number of specimens diagnosed as positive when the NNKT was used . False-positive results were not recorded in the NNKT.

J Med Microbiol, 1988 Mar, 25(3), 167 - 74
Measurement of hypoxanthine incorporation in purified suspensions of Mycobacterium leprae: a suitable method to screen for anti-leprosy agents in vitro; Wheeler PR; The rate of incorporation of hypoxanthine was measured in suspensions of Mycobacterium leprae, with and without added anti-leprosy agents . Dapsone, clofazamine and brodimoprim, as well as other benzylpryimidines, inhibited hypoxanthine incorporation, and their minimum inhibitory concentrations for incorporation with intact M . leprae were near the minimum inhibitory concentrations at which the agents have antibacterial effects . At sub-inhibitory concentrations for hypoxanthine incorporation, some combinations of benzylpyrimidines and dapsone were inhibitory, suggesting that synergic effects of anti-leprosy agents might also be detected by the inhibition of hypoxanthine incorporation . Thus, demonstration of inhibition of hypoxanthine incorporation in M . leprae could be a rapid method for screening anti-leprosy agents and especially for preliminary testing of new, potential anti-leprosy agents . The rate of hypoxanthine incorporation was generally lower in suspensions of M . leprae with lower viability, but it was not proportional to viability so the technique would not be suitable for accurate determination of viability.

Int J Clin Pharmacol Ther Toxicol, 1988 Mar, 26(3), 162 - 4
Pharmacokinetics of a new oral antibacterial agent, ofloxacin, in dentistry and oral surgery; Bedeschi G et al.; The new oral antibacterial agent, ofloxacin, was administered for prophylactic purposes to a group of 12 patients with dental and oral inflammatory processes requiring oral surgery . Drug concentrations in serum, saliva and gingival mucosa were assayed at different times after administration of the drug . Good serum, salivary and gingival mucosal tissue concentrations were achieved.

Jpn J Antibiot, 1988 Mar, 41(3), 331 - 7
{Changes in concentration of cefotetan in blood and lung tissue after intravenous administration}; Ishikawa M et al.; Cefotetan (CTT), a newly-developed cephamycin antibiotic, has been used widely for the treatment of various infectious diseases because of its excellent antibacterial potency and dynamic transport in vivo . Although the drug transfer to almost every organ, tissue, and body fluid has been studied, only a few reports are available regarding the transfer to lung tissue . In the present study, 1 g of CTT was intravenously injected in a single dose to each of 22 patients subjected to pulmonary resection . Subsequently, its concentrations in blood and lung tissue were measured in sequence . The degree of transfer of the drug to the lung tissue was calculated to evaluate the pharmacodynamics of CTT in vivo . The following results were obtained in this analysis . 1 . The T1/2(beta) of the concentration in blood was 4.18 hours, and AUC0-infinity was 478.7 micrograms.hr/ml . 2 . Cmax in the lung tissue was 31.5 micrograms/g, and Tmax was 0.83 hour, and tissue concentrations decreased in parallel to blood concentrations . CTT was transferred to the lung tissue to achieve high concentrations following an intravenous administration . Since high concentrations are maintained for a long period of time, this antibiotic is expected to exert an excellent effect in the prevention and the treatment of respiratory infections.

J Antibiot (Tokyo), 1988 Mar, 41(3), 275 - 81
New antibiotics 4181-A and B from Streptomyces griseus; taxonomy, fermentation, isolation and characterization; Otani T et al.; The new antibiotics 4181-A and B were isolated from the fermentation broth of Streptomyces griseus, a soil isolate . Their molecular formulae were determined as C29H21NO9 and C28H19NO9, respectively . The UV, IR and NMR spectra suggest that they possess a quinone moiety in their structures . They were found to have antibacterial, antifungal and antitumor activity.

Eur J Biochem, 1988 Mar 1, 172(2), 371 - 6
The structure of the gene for cecropin B, an antibacterial immune protein from Hyalophora cecropia; Xanthopoulos KG et al.; Pupae of the moth Hyalophora cecropia respond to an injection of live bacteria by the production of a potent antibacterial activity . The broad-spectrum property of this activity is due chiefly to two small proteins, cecropins A and B . Sequences of the proteins showed them to be homologous and to contain 37 and 35 amino acid residues respectively . The subsequent isolation of two cDNA clones for cecropin B showed that this protein is made as a prepro molecule composed of 62 amino acid residues . We have now prepared a genomic bank and studied four genomic clones for cecropin B . The coding regions were found in two neighbouring BglII fragments, one 0.79 kb and another varying in size from 3.1 kb to 4.9 kb for different clones . One transcriptional unit for preprocecropin B was sequenced and found to be 1035 bp long with a single intron, 514 bp in size . A conserved, insect specific cap site, ATCATTC, was identified by S1 mapping and primer extension experiments . Indications were found for the presence of multigene families and multicopy genes.

J Pharm Pharmacol, 1988 Mar, 40(3), 211 - 2
Kinetic mechanism for the intestinal absorption of ofloxacin; Prieto JG et al.; The absorptive behaviour of ofloxacin, a quinolone antibacterial agent, was studied following recirculation in small intestine of both male and female rats, at initial doses ranging from 0.125 to 5 mg mL-1 . A saturable Michaelis-Menten process is suggested to explain the intestinal absorption . No significant differences were found in the absorption parameters per metabolic weight unit.

J Biol Chem, 1988 Feb 5, 263(4), 1622 - 7
Bacterial N-succinyl-L-diaminopimelic acid desuccinylase . Purification, partial characterization, and substrate specificity; Lin YK et al.; The enzyme N-succinyl-L-diaminopimelic acid desuccinylase from Escherichia coli has been purified 7,100-fold to apparent homogeneity . The enzyme is part of the diaminopimelic acid-lysine pathway in bacteria and catalyzes the hydrolysis of N-succinyl-L-diaminopimelic acid to produce L-diaminopimelic acid and succinate . The enzyme exists as a mixture of dimeric and tetrameric species of identical subunits of molecular weight approximately 40,000 . Activity was completely abolished following dialysis of the enzyme against metal chelators . Cobalt(II) and zinc were effective in restoring the activity . The apparent affinities of the apoenzyme for cobalt and zinc were similar (Kd values near 1 microM) and the cobalt enzyme was 2.2-fold more active than the zinc enzyme . The Km and turnover number for the hydrolysis of the natural substrate, N-succinyl-L-diaminopimelic acid, were 0.4 mM and 16,000 min-1, respectively . The substrate specificity of the enzyme was defined by preparing a number of substrate analogues that systematically lack the various functional groups present in the molecule . These studies show that the enzyme is highly specific for the natural substrate . These properties of N-succinyl-L-diaminopimelic acid desuccinylase and the fact that the enzyme is essential for bacterial growth make it an ideal target for the development of inhibitors with potential antibacterial activity.

Jpn J Antibiot, 1988 Feb, 41(2), 173 - 9
{Basic and clinical studies on ceftriaxone in perinatal infections}; Soma A et al.; Basic and clinical investigations were conducted on ceftriaxone (CTRX), a cephem antibiotic with a wide antibacterial spectrum and with especially high activity against Gram-negative bacteria . The results obtained are summarized as follows: 1 . CTRX, following intravenous drip infusion of 1 g, had a serum half-life of 5.8 hours, which is longer than that of any other existing cephem antibiotics . 2 . The level of CTRX in the umbilical cord serum 6 hours after intravenous drip infusion of 1 g was at a satisfactory level, 15 micrograms/ml . 3 . The CTRX was remarkably effective or effective in 9 cases, and the activity was high even in cases where penicillin or other third-generation cephems were ineffective . These results seem to indicate that CTRX may be effective in perinatal and intrauterine fetal infections.

Burns Incl Therm Inj, 1988 Feb, 14(1), 62 - 5
Plasticized polyvinyl chloride film as a primary burns dressing: a microbiological study; Milner RH et al.; Twenty-four patients were studied after the application of plasticized polyvinyl chloride (PVC) film as a temporary burns dressing . The burns were assessed as being partial thickness (nine patients) and full thickness (15 patients) in depth and involving 2 per cent to 35 per cent of the body surface area . Microbiological cultures were performed on the exudate beneath the plasticized PVC film and then at each dressing change until the burn was healed . Bacterial isolates showed no unexpected organisms and there was no predominant organism to suggest contamination from the plasticized PVC film . Indeed, bacteria were only rarely isolated from the initial exudate (three of 37 burn wounds), and subsequent bacterial cultures did not differ from those normally found in burn wounds . In addition, incorporation of the plasticized PVC film into nutrient broth and agar with Staph, aureus and Ps . aeruginosa did not influence the recovery of these organisms, indicating that plasticized PVC film does not exert any antibacterial effect.

Anaesthesist, 1988 Feb, 37(2), 112 - 9
{Relation of hypoxia and edema of the intestinal wall and skin to colloid osmotic pressure}; Lundsgaard-Hansen P et al.; Whereas the impact of colloids and crystalloids on hypoxia and edema has been extensively debated with respect to pulmonary function, their corresponding effects on the systemic circulation have been largely ignored . Manifest edema of the intestine and skin develops, however, when the serum colloid osmotic pressure (COP) is lowered to 15 mm Hg or less by crystalloid infusions . Hypoxia of wounds, which may be aggravated by crystalloids, impairs healing and antibacterial defense, and its has been speculated that edema and/or hypoxia of the intestine may be associated with postoperative gastrointestinal dysfunction . We therefore studies the relationship between lowering and restoration of the COP, the pO2 of the intestinal surface and skin, and tissue edema . We generated an acute hypoproteinemic fluid overload reducing the COP from around 20 to 10 mm Hg in 56 rabbits by means of a 50% plasma loss and excess replacement with Ringer's lactate . We measured the COP with a membrane having a cut-off level of 20,000 d, the cardiac output (with derivation of further hemodynamic data) with an electromagnetic flow probe around the ascending aorta, and the tissue pO2 (pO2t) in mm Hg with the Dortmund 8-channel surface electrode . After 30 min without infusion (Fig . 1), we assigned 14 animals each at random to 4 treatment groups: (1) no treatment (O); (2) 20% albumin 7.5 ml/kg (A); (3) furosemide 2 mg/kg i.v . given three times at 30-min intervals (F); and (4) the combination of both agents (AF) . During the infusion-free interval, the cardiac output and pO2t fell by 20%-30% of baseline (Table 1).(ABSTRACT TRUNCATED AT 250 WORDS)

Med Hypotheses, 1988 Feb, 25(2), 89 - 92
Multiple sclerosis is a chronic central nervous system infection by a spirochetal agent; Marshall V; Multiple Sclerosis (MS) is a chronic central nervous system (CNS) infection similar to Lyme Disease or Neurosyphilis in its latency period, pathogenesis, symptoms, histopathology and chronic CNS involvement . It does not have as yet a fully identified spirochetal etiological agent . Much research and clinical support for this hypothesis was published before 1954 and is based on silver staining of neural lesions, animal isolation of the etiologic agent and the characteristic symptoms and pathogenesis of the disease . If this hypothesis is correct, the disease should be treatable with antibacterial agents that penetrate the CNS (such as high dose antibiotics), diagnosible by specific immunological tests, and preventable by early treatment or by the use of vaccines in high risk populations.

J Antibiot (Tokyo), 1988 Feb, 41(2), 181 - 92
Studies on cephalosporin antibiotics . II . Synthesis, antibacterial activity and oral absorption of 3-alkoxycarbonylmethoxy-7 beta-{(Z)-2-(2-aminothiazol-4-yl)-2-(O-substituted oxyimino)-acetamido}cephalosporins; Yokoo C et al.; The synthesis, antibacterial activity and oral absorption in rats of 3-alkoxycarbonyl-methoxy-7 beta-{(Z)-2-(2-aminothiazol-4-yl)-2-(O-substituted oxyimino)acetamido}cephalosporins (1) are described . In this cephalosporin series, 7 beta-{(Z)-2-(2-aminothiazol-4-yl)-2-(carboxy-methoxyimino)acetamid o} cephalosporins (1b, 1i and 1j) with a lower alkoxycarbonylmethoxy group at the C-3 position of a cephem nucleus exhibited not only potent activity against Gram-negative bacteria but also good oral absorption in rats . Structure-activity relationships of 1 are also presented.

J Antibiot (Tokyo), 1988 Feb, 41(2), 170 - 80
Studies on cephalosporin antibiotics . I . Synthesis, antibacterial activity and oral absorption of new 3-(O-substituted)-7 beta-{D-alpha-amino-alpha-(4-hydroxyphenyl)acetamido}cephalosporins; Yokoo C et al.; The synthesis, antibacterial activity and oral absorption of new 7 beta-{D-alpha-amino-alpha-(4-hydroxyphenyl)acetamido}cephalosporins (1) with various O-substituents at the C-3 position of a cephalosporin nucleus are described . Of these, the cephalosporins (1b-1e) having an alkoxycarbonylmethoxy group at the C-3 position showed good oral absorption in rats as well as potent activity against Gram-positive bacteria . The structure-activity relationships of 1 are also presented.

Infect Control Hosp Epidemiol, 1988 Feb, 9(2), 59 - 65
Stress ulcer prophylaxis and ventilation pneumonia: prevention by antibacterial cytoprotective agents?
Daschner F, Kappstein I, Engels I, Reuschenbach K, Pfisterer J, Krieg N, Vogel W.
The gastric and tracheal flora of 142 consecutive patients receiving stress ulcer prophylaxis were investigated, identifying identical isolates by typing . Furthermore, the growth pattern of normal respiratory bacteria and organisms causing ventilation pneumonia at different pH values and the in vitro effect of sucralfate and bismuth subsalicylate on these bacteria in simulated gastric fluid were studied . The results obtained were as follows: (1) with rising gastric pH bacterial counts in gastric aspirates, especially gram-negatives, increased significantly; (2) in 45 (31.7%) of the patients identical organisms were first isolated in gastric samples and one to two days later in tracheal secretions; (3) ventilation pneumonia was significantly more frequent in patients with high gastric pH; (4) pathogens causing ventilation pneumonia grew well in simulated gastric fluid at higher pH values, unlike normal respiratory organisms; and (5) sucralfate and bismuth subsalicylate showed antibacterial activity against frequent causative organisms of ventilation pneumonia.

Blood, 1988 Feb, 71(2), 383 - 7
Clinical factors influencing the efficacy of pooled platelet transfusions; Bishop JF et al.; To determine the relative importance of clinical factors on the efficacy of platelet transfusions, 941 pooled platelet transfusions from HLA-unmatched donors were studied prospectively in 133 patients with bone marrow failure . Multiple linear regression analyses identified the major factors influencing one-hour-corrected increments (CI) as prior splenectomy, bone marrow transplantation, disseminated intravascular coagulation, concurrent intravenous amphotericin B, splenomegaly, and HLA antibody grade . The relative impact of these factors on CI has been quantitated by using a formula developed from these data . A linear relationship was demonstrated between increasing percentage of HLA antibody grade and decreasing CI . A number of other factors were less important in the linear regression model than the aforementioned major factors . These included platelet-specific antibodies, concurrent antibacterial antibiotics, clinical bleeding grade, and temperature . Factors that did not influence CI included the number of prior platelet transfusions, prior granulocyte transfusions, prior red cell transfusions, infection, age, blood group, diagnosis, sex, pretransfusion platelet count, prior pregnancies, and concurrent antineoplastic drugs . This study identified major clinical factors that significantly influenced CI and were major causes of refractoriness to pooled platelet transfusions.

Clin Pharmacokinet, 1988 Feb, 14(2), 71 - 95
Pulse dosing versus continuous infusion of antibiotics . Pharmacokinetic-pharmacodynamic considerations; LeBel M et al.; The issue of whether it is better to administer antibiotics as an intermittent bolus dose or a continuous intravenous infusion has been debated for several decades . This paper reviews the extensive literature on the topic, considering both the pharmacokinetic and pharmacodynamic aspects of antibacterials as well as experimental results from studies conducted in vitro, in animals and in humans . It is evident from reviewing the literature that neither mode of administration is clearly superior to the other . The decision regarding the mode of administration must take into account the antibiotic being used, the bacteria, the patient and the infection, as well as the pharmacokinetics of the particular drug in the individual patient . The minimum inhibitory concentration (MIC) and the minimum bactericidal concentration (MBC) are useful indicators of the relative in vitro effectiveness of antibiotics, but it is not clear what relevance these parameters have to the desired antibiotic concentrations in vivo . Furthermore, questions of serum vs tissue fluid concentrations, peak concentrations vs AUC, and free vs total concentration are all important issues to consider in assessing the optimal mode of administration . The importance of newer indices such as the post-antibiotic effect are now beginning to be recognised . A number of scientists are actively engaged in developing a system to identify the most appropriate mode of administration based upon the integration of an antibiotic's pharmacodynamics and pharmacokinetics . Within the next few years we anticipate that appropriate guidelines should have been developed to aid the optimisation of parenteral administration, at least for some antibiotics.

Surg Clin North Am, 1988 Feb, 68(1), 41 - 55
Clinical assessment of host defense; Tellado-Rodriguez J et al.; Host defense mechanisms are a determinant of infection . Anergy in surgical patients is a signal of broadly based immune deficits, which include abnormalities in specific and local nonspecific antibacterial defenses and related life-threatening sepsis . Analysis of these abnormalities and other risk factors allows us to generate a long-predictive equation of individual probability of death.

Surg Clin North Am, 1988 Feb, 68(1), 181 - 97
Infection in the compromised host; Deitch EA; In spite of the development of successive generations of more powerful antibiotics, sepsis remains a common cause of death in the surgical patient . This fact is not surprising, since it is of little importance which organism is causing the infection if the patient's intrinsic antibacterial defenses cannot respond . Realization of the limitations of antibiotic therapy has prompted many investigators to study the immune and inflammatory systems with the ultimate goal of improving host defenses and increasing survival . In this article the local and systemic antibacterial defense systems have been reviewed . It is clear that the immunocompromised state is associated with multiple defects of the humoral and cellular components of both the nonspecific host defense system and the specific immune defense system . However, although consensus has not been reached on either the mediators responsible for the immunocompromised state or the prognostic and clinical significance of many of the described defects, work in this field is progressing rapidly . Nonetheless, knowledge that the host's antibacterial defense systems can be aided by good surgical technique, nutrition, appropriate use of antibiotics, and the sterile care of invasive catheters, lines, and tubes is critical in the prevention of fatal infections in the immunocompromised patient . When more information becomes available concerning the complex interrelations between the various cellular and humoral components of the host defense systems and their mediators and the symbiotic relations between man and his bacterial flora, it should be possible to develop specific strategies for the clinician to use to reduce the risk of infection in the high-risk surgical patient . Thus, in the future it may not be unusual for the clinician to alter the immunologic system of the host by the use of immunomodulators or vaccines to increase the host's resistance to infection . On the other hand, by manipulating the complex interrelations between the host and the indigenous bacterial flora, it may be possible to prevent the development of opportunistic infections originating from the gastrointestinal tract.

Antimicrob Agents Chemother, 1988 Feb, 32(2), 279 - 81
In vitro activity of LY146032 alone and in combination with other antibiotics against gram-positive bacteria; Debbia E et al.; The antibacterial activity of LY146032 alone and in combination with other drugs was assayed against gram-positive isolates . Synergism was found when LY146032 was combined with netilmicin, amikacin, imipenem, and fosfomycin by both checkerboard and time-kill tests . Indifference predominated when LY146032 was combined with teicoplanin, vancomycin, and rifampin . Under no circumstances and with no combinations was an antagonistic effect detected.

Antimicrob Agents Chemother, 1988 Feb, 32(2), 190 - 4
Inhibitory effects of quinolone antibacterial agents on gamma-aminobutyric acid binding to receptor sites in rat brain membranes; Tsuji A et al.; The specific binding of 3H-labeled gamma-aminobutyric acid ({3H}GABA) to synaptic plasma membranes from rat brains was inhibited by various quinolonecarboxylic acid derivatives (quinolones), and these inhibitions were concentration dependent . The binding of {3H}muscimol to GABAA sites was also inhibited . These inhibitory potencies differed widely among the quinolones examined . The Dixon plots showed that a newly developed difluorinated quinolone, NY-198 {1-ethyl-6,8-difluoro-1,4-dihydro-7-(3-methyl-1-piperazinyl)-4-oxo-3- quinolinecarboxylic acid hydrochloride}, competitively inhibits the receptor bindings of {3H}GABA and {3H}muscimol . In conclusion, our findings suggest that the inhibition of GABA binding to receptors (including uptake sites) in the brain may be involved in the induction of epileptogenic neurotoxicities by quinolones.

J Antimicrob Chemother, 1988 Feb, 21 Suppl B, 1 - 18
Alteration of bacterial DNA structure, gene expression, and plasmid encoded antibiotic resistance following exposure to enoxacin; Courtright JB et al.; Enoxacin inhibits growth of Escherichia coli K12 strains primarily by binding to the GyrA subunit of DNA gyrase (topoisomerase II); strains with gyrA, but not gyrB, mutations are less susceptible to the bactericidal effects of this agent . In sensitive strains, enoxacin completely inhibits DNA synthesis within 5 min and produces drug-gyrase-DNA complexes at numerous sites throughout the E . coli chromosome, as shown by the formation of linear DNA molecules after detergent treatment . Enoxacin, even at subminimal inhibitory concentrations, induces the bacterial SOS system, even in partially resistant gyrA strains . This drug also inhibits the induced expression of the lacZ encoded beta-galactosidase, regardless of whether this gene is located on the chromosome, a low copy number F' plasmid or high copy number Col E1 related plasmids . This inhibition of gene expression at subminimal inhibitory concentrations is likely to be a factor, in addition to gyrase inhibition, in the elimination of Col E1 plasmids and to the reduction in R plasmid conjugal transfer . Enoxacin enhances the bactericidal effects of kanamycin in both in-vitro and in-vivo models, suggesting that this quinolone may be effective in the treatment of infections due to strains resistant to antibacterials as a consequence of plasmid encoded resistance determinants.

Biochem Biophys Res Commun, 1988 Jan 29, 150(2), 877 - 82
Erythromycin and its derivatives with motilin-like biological activities inhibit the specific binding of 125I-motilin to duodenal muscle; Kondo Y et al.; Erythromycin, one of the macrolide antibiotics, and its derivatives had been found to mimic actions of exogenous motilin, a gastrointestinal peptide hormone . We found that some of the macrolide compounds inhibited the specific binding of 125I-motilin to rabbit duodenum muscle at 15 C in a dose-dependent fashion . The inhibitory activity of several macrolides examined did not relate to their antibacterial activity but to their motilin-like activity . A 50% inhibition by EM536, a non-antibacterial erythromycin derivative with the highest motilin-like activity, was obtained at 3-40 nM and little higher than that of non-radioactive motilin (5-6 nM) under the present conditions . The results suggest that erythromycin and its derivatives mimic physiological actions of motilin by acting as agonists for a motilin receptor.

Biochem Biophys Res Commun, 1988 Jan 29, 150(2), 540 - 4
Novel feature of expression of the sarcotoxin IA gene in development of Sarcophaga peregrina; Nanbu R et al.; The expressions of the sarcotoxin IA and IIA genes were investigated . Although both these antibacterial proteins were synthesized by the fat body and secreted into the hemolymph in the same way when the body wall of third instar larvae of Sarcophaga peregrina was injured, the expressions of their genes during development of this insect were different . The sarcotoxin IA gene was activated transiently in the embryonic and pupal stages, whereas the sarcotoxin IIA gene was totally inactive in these stages . These results suggest that sarcotoxin IA plays a role in the development as well as the defence mechanism of Sarcophaga.

Eur J Biochem, 1988 Jan 15, 171(1-2), 17 - 22
Insect immunity . Purification and characterization of a family of novel inducible antibacterial proteins from immunized larvae of the dipteran Phormia terranovae and complete amino-acid sequence of the predominant member, diptericin A; Dimarcq JL et al.; Injury or injection of live bacteria into third instar larvae of the dipteran insect Phormia terranovae results in the appearance in the haemolymph of at least five groups of heat-stable, more or less basic peptides with antibacterial activity against Escherichia coli . Three of these peptides have been purified . The amino acid sequence has been completely established for one of these and partially (first 40 residues from the N-terminus) for the two others . The sequences show marked homologies indicating that the three peptides belong to a common family . They are not related to other known antibacterial peptides from insects {lysozymes, cecropins (including sarcotoxin I) and attacins} . We propose the name of diptericins for this new family of antibiotic molecules.

Cancer Res, 1988 Jan 15, 48(2), 346 - 50
Dependence of the in vitro antiproliferative activity of recombinant human gamma-interferon on the concentration of tryptophan in culture media; de la Maza LM et al.; In addition to its antiviral and antibacterial activities, recombinant human gamma-interferon (rHuIFN-gamma) can exert an antiproliferative effect on human cell lines . The mechanisms involved in this antiproliferative activity are poorly understood, but it is known that IFN-gamma can induce indoleamine 2,3-dioxygenase, which enhances tryptophan metabolism and thus depletes the cellular pool of this amino acid . In the present study we have examined the effect of different tryptophan concentrations on the antiproliferative activity of rHuIFN-gamma on four human tumor cell lines, HeLa 229, HEp-2, A549, and T24 . Cells were grown in the presence of rHuIFN-gamma (0.01 to 100 ng/ml) and/or tryptophan (10 to 400 micrograms/ml) for 7 days at which time they were counted . rHuIFN-gamma (4 ng/ml) inhibited the growth of A549 and T24 cells by 50% . Hep-2 and HeLa 229 cells were more sensitive to the rHuIFN-gamma induced antiproliferative effects, requiring only 0.4 ng/ml for a 50% inhibition . Addition of tryptophan to the media at concentrations from 10 to 100 micrograms/ml resulted in a significant blockage of the antiproliferative activity of rHuIFN-gamma . For example, when 50 micrograms/ml of tryptophan were added to the media, 10 times more rHuIFN-gamma (4 ng/ml) was needed to inhibit HeLa 229 cells by 50% of the control . The A549 was the most sensitive cell line to the modulatory activity of the tryptophan . Addition of 10 micrograms/ml of tryptophan changed the amount of rHuIFN-gamma needed to produce a 50% inhibition from 4 ng/ml to 100 ng/ml . In summary, in the four human tumor cell lines tested, the antiproliferative activity of rHuIFN-gamma could be modulated by the concentration of tryptophan in the media.

FEBS Lett, 1988 Jan 4, 226(2), 303 - 6
Tuftsin stimulates growth of HL60 cells; Bump NJ et al.; Many functions of monocyte/macrophage and granulocyte are activated by tuftsin; principally phagocytosis, motility, immunogenic stimulation, antibacterial and antineoplastic activities . Here it is shown that tuftsin stimulates HL60 growth to twice the control rate . The uptake of {3H}uridine and {3H}leucine in a pulse of 30 min was also double that of the control . The uptake of thymidine was not stimulated.

Life Sci, 1988, 43(3), 221 - 7
The role of leukotoxin (9,10-epoxy-12-octadecenoate) in the genesis of coagulation abnormalities; Sugiyama S et al.; This study was designed to clarify whether or not leukotoxin (9, 10-epoxy-12-octadecenoate), which is biosynthesized by neutrophils, might be involved in the genesis of coagulating abnormalities . Twelve dogs were divided into 2 groups . In the test group (n = 6), 100 mumol/kg of leukotoxin was injected intravenously, and in the control group (n = 6), 100 mumol/kg of linoleate was injected . In each group, a series of blood samples were collected and used for coagulation studies . After the end of the experimental period, a histological study was performed on organs removed from the dogs . In the leukotoxin group, fibrin and fibrinogen degradation products (FDP) was increased time-dependently . Fibrinogen was decreased, and prothrombin time and activated partial thromboplastin time were prolonged in parallel with the increase in FDP . A decrease in number of platelets was also observed . Intravascular coagulation was observed in sections of lung . These data were compatible with a diagnosis of disseminated intravascular coagulation (DIC) . No significant changes in these parameters were observed in the linoleate group . Leukotoxin has been confirmed to show antifungal and antibacterial activity, and its production might be a defensive response to infection . Over-production of leukotoxin associated with severe infection might therefore account for infection-induced DIC.

Folia Microbiol (Praha), 1988, 33(3), 198 - 207
Antibacterial activity of some alpha-substituted 2-methyl-5-nitrofurans; Ghannoum MA et al.; The minimum inhibitory concentration values against Gram-negative and Gram-positive bacteria were determined and compared for a selected group of synthesized alpha-substituted 2-methyl-5-nitrofuran derivatives . In vitro oxidation of thiols to disulfides by 2-(iodomethyl)-5-nitrofuran indicated that oxidation of enzyme-thiol groups to disulfide bonds was a possible mode of action; but was discounted by noninhibition of thiol enzymes by these compounds . Electron-microscopic studies of the morphology of bacteria after treatment with these derivatives showed the formation of unusual elongation, branching and atypical rod shapes in E . coli, while S . aureus manifested multibud formation with some cytoplasmic protrusions . The possible mode of action of these compounds is discussed.

Int J Clin Pharmacol Res, 1988, 8(2), 107 - 10
Penetration of roxithromycin in bronchial secretions; De Rose V et al.; Roxithromycin sputum and serum concentrations after administration of therapeutic doses (150 mg in a single dose) were evaluated in six patients . Blood samples and pooled sputum samples were collected at corresponding time intervals up to 24 h after drug administration . Roxithromycin sputum levels were found to be almost always above serum concentrations, the highest sputum levels being 5.85 +/- 2.5 micrograms/ml in the interval ranging from 2 to 4 h after drug administration . Due to its antibacterial spectrum and favourable pharmacokinetic properties, roxithromycin, like other macrolide antibiotics, seems to be particularly indicated in the treatment of respiratory tract infections.

Antibiot Khimioter, 1988 Jan, 33(1), 67 - 71
{Antibiotic therapy of angiogenic sepsis}; Navashin S et al.; Introduction to medical practice of new penicillins, cephalosporins and aminoglycosides is one of the chief reserves for increasing efficacy of antibacterial therapy . The main schemes of antibiotic use in treatment of sepsis and individual regimens controlled by laboratory findings are discussed . Optimization of antibiotic therapy schemes is based on pharmacokinetic studies, quantitative assay of antibiotic sensitivity and determination of antibacterial activity of serum and other biosubstrates at definite periods after antibiotic administration . In vitro time course investigation of the bactericidal effect of gentamicin, azlocillin and cefotaxime on pathogens of purulent infections at various sizes of the inoculum provided prediction of the antibiotic therapy efficacy in various purulent septic infections . It is indicated that rational use of antibiotics markedly increases efficacy of sepsis therapy and improves social and economic indices of the treatment.

J Burn Care Rehabil, 1988 Jan-Feb, 9(1), 106 - 17
The Everett Idris Evans memorial lecture--1987: twenty-five years' experience treating burns; Ohura T; For this presentation, the author selected a few highlights and summarized some of his main interests drawn from 25 years' experience as a surgeon in the Department of Plastic Surgery at Hokkaido University . The four major topics addressed are (1) kinetics and the effect of antibacterial agents and other drugs on the burn wound; (2) study of inhalation injuries and anticoagulant therapy in severe burns; (3) wound healing and the effects of artificial skin substitutes; and (4) reconstructive surgery in burned patients.

Can J Vet Res, 1988 Jan, 52(1), 129 - 33
The effect of certain topical medications on healing of cutaneous wounds in the common garter snake (Thamnophis sirtalis); Smith DA et al.; The effects of four topical medications on the rate and character of healing of cutaneous wounds were studied in six common garter snakes (Thamnophis sirtalis) held at an ambient temperature of 30 degrees C . Two sets of five 6 to 8 mm round excisional wounds, four test and one control site in each set, were created on the dorsolateral body wall of each snake . Wounds were examined daily and treated for ten days, then the snakes were killed and sections of all wounds were examined by light microscopy . Composite scores, derived by ranking each treatment group in relation to the control group (control score = 0) for each of 22 characteristics associated with wound healing, were used to compare the overall effects of each treatment . Statistical comparisons were made between groups for 20 characteristics . Wounds treated with a polyurethane film merited a score of +12 and had significantly more advanced healing than untreated controls for three characteristics . Wounds treated with an ointment containing scarlet red scored +6 but healing was not significantly greater than controls . Wounds treated with an antibacterial spray powder and an antibacterial ointment healed more slowly than controls and had scores of -6 and -12 respectively.

Biull Eksp Biol Med, 1988 Jan, 105(1), 58 - 60
{Macrophage activation induced by a synthetic antioxidant}; Freidlin IS et al.; The effect of a synthetic antioxidant 2-tretbutyl-3-hydroxypyridine (TBHP) on the function of murine peritoneal macrophages (MP) has been studied . A direct contact of TBHP with MP in vitro increased the activity of a key enzyme of glucose monophosphate graft--glucose-6-phosphate dehydrogenase and the proportion of flattened MP . as compared to the control . Upon intraperitoneal MP injection the number of MP's in the abdominal cavity of mice increased . They differed from control MP's in enhanced flattening and phagocytosis . In mice with preinduced defect of abdominal clearance TBHP contributed to the recovery of the normal level of antibacterial protection . In all the in vitro and in vivo tests studying its activating effect on MP, the synthetic antioxidant was not inferior to the standard MP activator--bacterial lipopolysaccharide.

Parasitology, 1988, 96 Suppl, S25 - 44
Molecular mechanisms involved in the transport of antibiotics into bacteria; Chopra I; Many clinically useful antibacterial drugs have intracellular target sites . Therefore, in order to reach their targets, these compounds must be able to cross bacterial outer and cytoplasmic membranes . Considerable information is available on the mechanisms by which antibiotics cross bacterial membranes and, in many cases, it is now possible to define the molecular basis of their uptake . Passage of drugs across the outer membrane of Gram-negative bacteria can occur by diffusion through porin channels (e.g . beta-lactams and tetracyclines), by facilitated diffusion using specific carriers (e.g . albomycin), or by self-promoted uptake (e.g . aminoglycosides and polymyxins) . Transfer of antibiotics across the bacterial cytoplasmic membrane is usually mediated by active, carrier-mediated, transport systems normally operating to transport essential solutes into the cell . For example, the antibiotic streptozotocin bears sufficient structural resemblance to N-acetyl-D-glucosamine to be transported by the phosphoenolpyruvate:phosphotransferase system, and D-cycloserine is recognized by the D-alanine, proton motive force dependent transport system . However, in some cases (e.g . tetracycline) although carrier-mediated transport is implied by the observation that drug uptake is energy dependent, the nature of the membrane carrier(s) responsible is unknown . Knowledge acquired from studies on bacterial peptide transport has been successfully used to deliver (or smuggle) amino acid mimetics disguised as peptides into the bacterial cell . These amino acid mimetics, although often poorly transported in their own right, are frequently potent inhibitors of bacterial peptidoglycan or lipopolysaccharide synthesis once they have gained access to the interior of the cell.

Infection, 1988, 16 Suppl 1, S3 - 13
Pharmacokinetics of ciprofloxacin; Bergan T et al.; The fluorination of piperazinyl substituted quinolones has led to an interesting development of a series of new broad spectrum antibacterial agents that may be administered orally as well as parenterally and are well tolerated . Norfloxacin was an early compound, later followed by ciprofloxacin, enoxacin, ofloxacin and pefloxacin . In this overview the emphasis will be on the most extensively studied compound including comparisons, where data are available, with norfloxacin and ofloxacin . Enoxacin and pefloxacin will be omitted due to their pattern of side effects, which at present curtail their therapeutic use . More recent substances such as fleroxacin and defloxacin have not been sufficiently investigated to be considered in this context.

Rev Infect Dis, 1988 Jan-Feb, 10 Suppl 1, S2 - 9
Aspects of chemistry in the development of the 4-quinolone antibacterial agents; Crumplin GC; The evolutionary route followed in the development of the new generations of 4-quinolone antibacterial agents, from the precursor of nalidixic acid to ciprofloxacin and ofloxacin (and beyond), is characterized by a paramount role for serendipity . All of the high-technology features such as fluorination, the presence of a piperazine ring at position 7, and the stereoisomerism of the molecule, represent only the combination of characteristics incorporated in earlier generations of nalidixic acid analogues . Although almost unprecedented levels of potency per mole have been attained along with effective broad-spectrum antibacterial activity and acceptable pharmacokinetic properties, all developments have been made and are being made in the absence of a proper knowledge of how these agents work against susceptible bacteria . The absence of this knowledge, along with our almost total ignorance of how the antibacterial activity relates to possible effects in Homo sapiens, is at present a barrier to the rational development of truly optimized 4-quinolones.

Quad Sclavo Diagn, 1988 Jan-Dec, 24(1-4), 203 - 12
{In vitro evaluation of the antibiotic effect of imipenen on bacterial strains isolated mostly from compromised patients}; Bartolucci M et al.; The antibacterial activity in vitro of Imipenem (N-formimidoyl-thienamycin) was studied on 237 recently-isolated nosocomial bacterial strains and compared with Aztreonam, Cefotaxime, Ceftazidime, Ceftriaxone, Piperacillin, Amikacin and Netilmicin through the determination of susceptibility by the Kirby-Bauer method . Taking into account that 65% bacterial strains, out of the examined ones, came from antibiotic high-pressure departments (45% from bone-marrow transplanted patients in the Hematological Department and 20% from Intensive Care Unit patients), the results obtained in vitro show an activity of Imipenem on Gram-negative bacteria as much as a 92.7% susceptibility and a 75.7% on Gram-positive bacteria; when compared with the activity of the other antibiotics, Imipenem shows a really excellent activity.

Clin Exp Rheumatol, 1988 Jan-Mar, 6(1), 35 - 9
Factors influencing the cytotoxicity of anti-bacterial sera for lymphocytes from ankylosing spondylitis patients; Archer JR et al.; Rabbit antisera to certain strains of Gram-negative bacteria are reported to be cytotoxic for the lymphocytes of about 80% of HLA-B27 positive patients with ankylosing spondylitis (AS) but not for the lymphocytes of healthy HLA-B27 positive individuals . The lymphocytes of normal individuals can, however, be made susceptible to lysis by antibacterial sera by incubation in spent supernatant from appropriate bacterial cultures . In an attempt to explain the failure of certain laboratories to reproduce these results we have tested a number of variables in the 51Cr-release complement-dependent cytotoxicity assay . We conclude that AS patients in London and Sydney carry the same antigen, that several different incubation media can be used for both the cytotoxicity assay of HLA-B27 positive AS cells and modification of normal B27 positive cells and that the cells used may be collected either in heparin containing media or after defibrination . Major requirements for success include a healthy sample of lymphocytes (preferably at a fairly high concentration), suitable antiserum from a rabbit repeatedly immunised with large numbers of bacteria, appropriate complement and efficient technique . However, as we have failed to repeat this test consistently in London, even using materials tested in this study, it seems that another, probably non-biological, factor is also important.

Curr Med Res Opin, 1988, 11(1), 64 - 72
Co-trimoxazole in patients with haematological malignancies: a review of 10-years' clinical experience; De Pauw BE et al.; Co-trimoxazole has been used in a hospital for over 10 years as a major antibacterial agent in the treatment of malignant haematological diseases . Routine selective gut decontamination with co-trimoxazole combined with colistine and an antifungal agent has led to a reduction in infections in neutropenic patients from 40% to 25% since the strategy was adopted, and this had been accompanied by a change in the most frequent pathogens, from Gram-negative to Gram-positive organisms . Co-trimoxazole has proved to be the drug of choice for Pneumocystis carinii infections . Finally, it is used as first-line therapy in febrile immunosuppressed patients who are not on selective decontamination, with an efficacy of over 90% . Apart from mild abdominal discomfort, an elevated allergy rate of 14% in patients with overt leukaemia is a major disadvantage . On the other hand, substantial prolongation of episodes of bone marrow aplasia has not been observed.

Int J Clin Pharmacol Res, 1988, 8(6), 457 - 61
Xibornol: multiple dose pharmacokinetics and diffusion in lung, tonsillar tissue and laryngeal mucosa; Scaglione F et al.; In ten patients with severe chronic bronchitis and in a further 23 with planned resection of lung, tonsils or larynx, 500 mg doses, single or multiple, of xibornol (6-isobronyl-3, 4-xylenol) were administered for an antibacterial effect . The pharmacokinetics and diffusion of the drug in the tissues were studied . A high diffusion and distribution value of xibornol was observed, with levels in the tissues constantly higher than that in the serum . The concentrations reached within the respiratory tract were adequate for their antibacterial effect.

Drugs, 1988, 35 Suppl 7, 39 - 42
Sulbactam/ampicillin versus cefoxitin for uncomplicated and complicated acute pelvic inflammatory disease; Hemsell DL et al.; In this study, 17 women were treated for uncomplicated acute pelvic inflammatory disease requiring hospitalisation for therapy, and 5 women were treated for the same infection complicated by pelvic abscesses . Treatment regimens were sulbactam 1g plus ampicillin 2g (14 women) or cefoxitin 2g (8 women) given by intravenous infusion every 6 hours . On the third day of therapy, a rash developed in 1 woman who was being successfully treated for uncomplicated disease with sulbactam/ampicillin . The other 21 women were cured . No other adverse clinical reactions and no significant abnormal laboratory results were observed with either regimen . Bacteriological efficacy, 98% for sulbactam/ampicillin and 94% for cefoxitin, closely paralleled clinical efficacy . Sulbactam, a suicide-type beta-lactamase inhibitor, appears to have restored and expanded the antibacterial activity of ampicillin.

Biomater Artif Cells Artif Organs, 1988, 16(4), 771 - 83
Collagen based biomaterials: an ideal way of increasing their resistance to infection; Gunasekaran S et al.; Collagen and gelatin containing biomaterials are relatively more susceptible to bacterial infection . Systemic administration or local delivery of antibiotics after implantation does not seem to solve the problem either effectively or easily . Antibiotics may be incorporated in the implant; but many, being water soluble, are quickly absorbed and not effective for adequate time periods . Resorcinol monoacetate (RMA) is a relatively water insoluble antibacterial agent which partially crosslinks collagen and has the potential to be an intrinsic antibiotic in collagenous bioprostheses . This study confirms the efficacy of RMA as a chemical that: (a) mildly crosslinks collagen at pH 3.5-4.5; (b) releases very slowly from the pretreated collagen sponge when washed in aqueous medium; (c) inhibits bacterial growth on the pretreated collagen sponges, at 2% (w/w) concentration, for at least 12 days; (d) remains biocompatible under treated conditions.

Ter Arkh, 1988, 60(7), 109 - 12
{Errors in the diagnosis of tuberculosis of the respiratory organs in a pulmonological hospital and the possibilities of their prevention}; Daniliak IG et al.; Respiratory tuberculosis in a pulmonary inpatient setting is not rare but, as a rule, is not diagnosed in time . Tuberculosis-directed alertness, especially in patients with an atypical lingering course of disease, the absence of the effect of nonspecific antibacterial therapy, risk factors (immunodeficiency state, diabetes mellitus, alcoholism, prolonged glucocorticoid therapy), and the disease-oriented screening permit early diagnosis of respiratory tuberculosis.

Graefes Arch Clin Exp Ophthalmol, 1988, 226(6), 539 - 41
Orbital cellulitis due to mucormycosis . A case report; Kotzamanoglou K et al.; A case of orbital cellulitis caused by mucormycosis developed in a patient subsequent to cataract extraction and during systemic steroid treatment for postoperative complications . Fatal mucormycosis is a rare disease usually beginning with a subcutaneous inflammatory lesion . As the subsequent development of orbital cellulitis is very rare, little has been published on this subject . In cases of subcutaneous mucormycosis, the diagnosis can easily be made by means of histologic examination of the lesion . However, early diagnosis is difficult in cases with orbital involvement, because the most common cause of orbital cellulitis is bacterial . Thus, orbital cellulitis caused by mucormycosis is often wrongly treated with antibacterial agents only, as histologic examination is neither easy nor part of any routine investigation . Therefore, a combined treatment using antibiotics and antifungal agents in immunusuppressed patients with this disease is advocated.

Chemotherapy, 1988, 34(5), 380 - 4
Importance of the mode of intravenous administration on cephotaxime concentration in bile . A comparison of bolus, drip infusion and bolus plus drip infusion; Miglioli PA et al.; Success of antibacterial therapy depends on many factors, among which the level reached at the site of infection is important . Drug concentration in tissues and body fluids can be related to the mode of administration . The aim of the present work was to study the levels of cephotaxime (CFX) in bile, after intravenous administration of 1 g by bolus, drip infusion and bolus plus drip infusion . The drug was detected by a microbiological method . The results indicate that passage of CFX from blood into bile is a carrier-mediated process, and bolus, in the case of CFX, is the best mode of administration.

Int J Vitam Nutr Res, 1988, 58(2), 171 - 7
Saliva concentrations of some selected proteins and glycoprotein markers in man after supplementary intake of beta-carotene; Lumikari M et al.; Vitamin A has profound effects on cell biology, morphology and function of excretory cells . In the present study we investigated the effect of supplementation with beta-carotene (provitamin A) on the secretion of salivary glycoproteins and some antibacterial components . Eighty-nine men, drawn from a larger double-blind pilot study among Finnish men of a high socio-economic standard, participated in this study which lasted for 60 days . The men were allocated either to beta-carotene supplementation of 20 mg a day or to placebo treatment . At the end of the study samples of stimulated whole and parotid saliva were collected and examined for total protein as well as hexosamine, sialic acid, thiocyanate and the activity of salivary peroxidase . The secretion rate of whole saliva was calculated and the activities of lysozyme, a bacteria aggregating glycoprotein (BAGP) and secretory IgA were measured in parotid saliva . Significantly higher levels of beta-carotene, but not retinol, were found in serum and whole saliva in the beta-carotene group compared to the placebo group . Retinol or beta-carotene could not be detected in parotid saliva . No difference was found either in saliva secretion rate or in the composition of whole or parotid saliva between the beta-carotene and the placebo group.

J Gen Microbiol, 1988 Jan, 134 ( Pt 1), 213 - 20
Biological and biochemical characterization of novel lipid-like antibacterial substances (mutalipocins) produced by Streptoccus mutans strain 32K; Kurita T et al.; Two novel antibacterial substances (designated mutalipocins) have been isolated from the culture supernatant of Streptoccus mutans strain 32K (serotype c) . The mutalipocins were purified by extraction of the culture supernatant with light petroleum (b.p . range 30-60 degrees C), followed by Lobar column chromatography on Lichroprep RP-8 . HPLC indicated that both mutalipocin preparations (ML-I and ML-II) were homogeneous . The Mr values of ML-I and ML-II were less than 1000 . Both mutalipocins were unaffected by treatment over the pH range 3.0-10.0, or with phospholipase A or proteolytic enzymes, but were partially inactivated by treatment with lipase or phospholipase C . ML-II was resistant to heat treatment . TLC indicated that ML-I and ML-II contained unsaturated, aldehyde and/or ketone, and ester groups . The inhibition of S . mutans by ML-I and ML-II was due to bactericidal, rather than bacteriostatic, activities . The antibacterial spectra of ML-I and ML-II were narrower and more species-specific than those of bacteriocins produced by other Gram-positive bacteria.

Infection, 1988, 16 Suppl 1, S51 - 4
Antibacterial treatment of otitis and sinusitis with ciprofloxacin and penicillin V--a comparison; Falser N et al.; 80 adult outpatients suffering from otitis media, sinusitis (maxillaris or frontalis) or peritonsillitis were treated with 500 mg ciprofloxacin b.i.d . (n = 40) or with 2 g penicillin V t.i.d . (n = 40) . The patients were randomly allocated . Three groups of patients resulted, clinically and bacteriologically evaluable, or only clinically evaluable because the isolated strains were resistant to ciprofloxacin or penicillin V or because no strains were isolated . Ciprofloxacin was superior to penicillin V; there were fewer resistant strains (one compared to 11), and the eradication rate (57% compared to 43%) as well as the clinical efficacy (60% compared to 48%) of ciprofloxacin were better than those of penicillin V--even in a daily dose of 6.0 g . Both treatments were well tolerated; side effects were neither reported nor found.

Pharmatherapeutica, 1988, 5(3), 198 - 203
{Comparative double-blind evaluation of a new topical antibacterial agent, mupirocin, compared with placebo in the treatment of skin and soft tissue infections}; Colin M et al.; Ninety-eight patients suffering from skin and soft tissue infections in the Cote d'Ivoire were treated topically with a new antibiotic, mupirocine, or with placebo in a double-blind study . Patients were allocated at random to receive one or other treatment, applying the ointment, supplied in identical tubes and of similar colour base, to the lesions 3 times a day for 5 days . Overall evaluation of clinical response to treatment showed that the results with mupirocine were significantly superior to those with placebo . No unwanted effects of treatment were observed in either treatment group.

G Batteriol Virol Immunol, 1988 Jan-Dec, 81(1-12), 96 - 116
{Bacterial resistance to antibiotics: biologic and ecologic aspects}; Cavallo G; After a short introduction on bacterial resistance to the antibiotics and on the importance of the problem of emergence of the resistant strains, the mechanisms responsible are discussed . There are three major ways by which bacteria resist beta-lactam antibiotics; these include: altered outer membrane permeability, production of beta-lactamase and diminished affinity of the PbPs . Production of beta-lactamase is by far the most frequently encountered; for this reason there has been a major effort in the past 20 year to design new beta-lactam antibiotics, but on the other side bacteria elaborate constantly new strategies against new antibiotics . Moreover the use of antibacterial agents over the past half century has elicited a widespread deployment of genes for resistance in population of bacteria throughout the world and is conditioning the evolution of microbes.

Acta Otolaryngol Suppl, 1988, 458, 174 - 80
Current concepts of pathogenesis of otitis media: a review; Lim DJ et al.; A number of important factors singly or in combination contribute to the pathogenesis of otitis media . These are poor tubal function, upper respiratory viral infection, bacterial adherence and nasopharyngeal flora, and immune status of the host . One of the important functions of the tubotympanum is to protect the middle ear from invading microbes . The host has available a number of strategies for this function including mucociliary protection, antibacterial secretory products, and specific immunodefenses . The microbes also possess the capability of escaping host defenses by enhancing their ability to adhere to mucosal surfaces, impairing mucociliary function and evading phagocytosis . Once microbes gain entrance to the middle ear, the microbes must overcome phagocytosis and immunodefense of the host, leading to otitis media . Recent data further indicate that specific qualitative and quantitative deficiencies in the immune system of children may predispose certain children to develop otitis media . These deficiencies appear to be in part due to a lack of maturity of the child's developing immune system as well as functional defects that are attributable to genetic or other unknown factors.

J Gynecol Obstet Biol Reprod (Paris), 1988, 17(7), 869 - 75
{Urogenital infection and male fertility}; Auroux M; There is disagreement as to the influence of urogenital infections on male fertility . The causative organisms are not the same according to different authors and ways in which the sperm are examined do not always seem to have the necessary bacteriological precision . A recent study carried out by us has however shown that Ureaplasma urealyticum and E . coli appear to be the bacteria that are most frequently met in cultures from the semen of infertile men . Changes that these bacteria can bring about are: --direct effects, in that the numbers of spermatozoa themselves are diminished as well as their motility, their morphology and their ability to fertilize . From this point of view the connection between the concentration of bacteria in relationship to the concentration of gametes could be important; --indirect effects, in so far as that infection should change the constituent qualities of the seminal fluid and thus have a secondary effect on spermatozoa, as for example the presence of large numbers of polynuclear cells or the formation of antisperm antibodies . Therapeutic trials, which could have helped solve the problem, do not yet seem to have been decisive . But considerable variations in sperm parameters, which by themselves can perhaps affect the antibacterial potency of seminal fluid, could explain why there are variations in success and failure . Finally, emphasis is placed on the need to stick to rigorous bacteriological protocols and to undertake at the same time well codified clinical, biological, epidemiological and experimental studies.

Clin Microbiol Rev, 1988 Jan, 1(1), 60 - 81
Legionnaires disease: historical perspective; Winn WC Jr; In the summer of 1976, a mysterious epidemic of fatal respiratory disease in Philadelphia launched an intensive investigation that resulted in the definition of a new family of pathogenic bacteria, the Legionellaceae . In retrospect, members of the family had been isolated from clinical specimens as early as 1943 . Unsolved epidemics of acute respiratory disease dating to the 1950s were subsequently attributed to the newly described pathogens . In the intervening years, the Legionellaceae have been firmly established as important causes of sporadic and epidemic respiratory disease . The sources of the infecting bacteria are environmental, and geographic variation in the frequency of infection has been documented . Airborne dissemination of bacteria from cooling towers and evaporative condensers has been responsible for some epidemics, but potable water systems are perhaps more important sources . The mode of transmission from drinking water is unclear . The Legionellaceae are gram-negative, facultative, intracellular pathogens . The resident alveolar macrophage, usually an effective antibacterial defense, is the primary site of growth . Cell-mediated immunity appears to be the most important immunological defense; the role of humoral immunity is less clear . Erythromycin remains the antibiotic of choice for therapy of infected patients, but identification and eradication of environmental sources are also essential for the control of infection.

Microb Pathog, 1988 Jan, 4(1), 15 - 20
Pulmonary secretions accelerate the metabolic rate of Escherichia coli; Ellison RT 3rd et al.; A number of studies have suggested that bronchoalveolar lavage fluid (BALF) contributes to intrapulmonary antibacterial host defense, however the mechanisms underlying this interaction have not been defined . To better understand the effect of BALF on bacteria, we measured the metabolism of bacteria in the presence of human or rabbit BALF . Escherichia coli oxygen consumption significantly increases with exposure to BALF (2.9 +/- 0.2 (SEM) nmol/min) compared to incubation in a saline-glucose solution alone (1.8 +/- 0.1); the rate of 1-{14C}-glucose utilization is comparably increased . The effect on oxygen metabolism is dose dependent . The surfactant phospholipids produce a small stimulation of oxygen metabolism, but the major effect is caused by phospholipid-poor material less than 10,000 daltons in size . The activity is heat stable, pH stable, and resistant to the effects of proteases . These studies demonstrate that factor(s) within BALF increase the metabolic rate of bacteria . Further work is required to determine if this bacterial respiratory burst is a pathogenic mechanism or a reparative response to BALF induced injury.

Rev Pneumol Clin, 1988, 44(3), 122 - 7
{Macrolides}; Aubert G; The first macrolides were marketed almost 30 years ago . These drugs constitute a homogeneous class of antibiotics with very similar mechanisms of action and resistance . Owing to their specific antibacterial spectrum and their mild side-effects, interest in macrolides has now been renewed, notably because of their activity against bacteria that develop within cells . Recent studies have provided additional information on their pharmacokinetic profiles, and notably on their tissue and intracellular distribution.

Proteins, 1988, 4(1), 31 - 47
Structure and energetics of ligand binding to proteins: Escherichia coli dihydrofolate reductase-trimethoprim, a drug-receptor system; Dauber-Osguthorpe P et al.; A study of the binding of the antibacterial agent trimethoprim to Escherichia coli dihydrofolate reductase was carried out using energy minimization techniques with both a full, all-atom valence force field and a united atom force field . Convergence criteria ensured that no significant structural or energetic changes would occur with further minimization . Root-mean-square (RMS) deviations of both minimized structures with the experimental structure were calculated for selected regions of the protein . In the active site, the all-atom minimized structure fit the experimental structure much better than did the united atom structure . To ascertain what constitutes a good fit, the RMS deviations between crystal structures of the same enzyme either from different species or in different crystal environments were compared . The differences between the active site of the all-atom minimized structure and the experimental structure are similar to differences observed between crystal structures of the same protein . Finally, the energetics of ligand binding were analyzed for the all-atom minimized coordinates . Strain energy induced in the ligand, the corresponding entropy loss due to shifts in harmonic frequencies, and the role of specific residues in ligand binding were examined . Water molecules, even those not in direct contact with the ligand, were found to have significant interaction energies with the ligand . Thus, the inclusion of at least one shell of waters may be vital for accurate simulations of enzyme complexes.

Vet Res Commun, 1988, 12(1), 67 - 75
A survey of some drugs commonly used in the camel; Ali BH; Specific recommendations for drug dosages for the camel are rare and doses for this species are usually extrapolated from those recommended for other species . The pharmacology and toxicity of drugs likely to be used in the camel needs to be further studied to ensure the efficacy and safety of these drugs in this species . Most of the reported work is on the chemotherapeutic efficacy of a few drugs long in use in other species against trypanosomiasis, mange and gastrointestinal nematodes . Areas of study most deficient are pharmacodynamics, pharmacokinetics and drug metabolism . The anatomical, physiological and biochemical peculiarities of the camel warrant more pharmacological and toxicological studies in this species . This article surveys the literature on the pharmacology, toxicity and therapeutic uses of some antiparasitic and antibacterial drugs and central nervous system depressants commonly used in the camel . It appears that camels are more susceptible to the toxic action of some trypanocidal drugs than other species . In certain cases they may metabolize some drugs differently . In general, the camel appears to be a good subject for analgesics and anaesthetics.

Tierarztl Prax, 1988, 16(2), 109 - 12
{Is a repeat treatment of antibiotic therapy necessary?}; Seeger K; Interrelations between host, bacterium and antibiotic compound in antibiotic therapy of bacterial infections are analysed . Some methods for the evaluation of antibacterial activity of antibiotics in vitro are described and their limits, in particular of the widely used MIC tests, are demonstrated . Data from trials comparing antibiotic applications once and twice a day as well as discussions in chemotherapy, concerning the applicability of in vitro results to therapy, are used to try to find practicable guidelines for the repetition of antibiotic therapy.

Polim Med, 1988, 18(4), 239 - 43
{Providing antibacterial properties to a vascular prosthesis made of polyethylene terephthalate fibers}; Georgiewa A et al.; We made the synthesis of a new antibacterial product satisfying the requirements and being similar to polyethylene terephthalate fibres PET from which implants designed for people are made . Proper solvents were worked out and the parameters of processing were determined . The vascular prostheses subjected to the antibacterial processing proved very good and longlasting antibacterial properties.

Acta Histochem, 1988, 83(2), 185 - 8
Immunohistochemical observations of lysozyme in the Paneth cells of specific-pathogen-free and germ-free mice; Satoh Y et al.; The localization of lysozyme, which may function as an antibacterial agent, was immunohistochemically studied on the mouse Paneth cell secretory granules showing bipartite substructures (central core and peripheral halo) . The lysozyme immunoreactivity was observed in the core, but not in the halo . Even in germ-free mice, Paneth cells have many secretory granules and their cores show lysozyme immunoreactivity . It seems likely that mice Paneth cells possess the ability to produce secretory granules containing lysozyme in disregard of the intestinal bacterial milieu.

J Clin Microbiol, 1988 Jan, 26(1), 62 - 6
Enzyme-linked immunosorbent assay for quantitation of attachment and ingestion stages of bacterial phagocytosis; Athamna A et al.; Research on phagocytosis of bacteria is often hampered by the inability to distinguish quantitatively between bacteria that have been ingested by phagocytic cells and those which are attached to the surface of the cells . A method using the enzyme-linked immunosorbent assay technique to simply and accurately measure the rate of bacterial ingestion by phagocytic cells is described . The method is based on the ability of antibacterial antibodies to bind to bacteria attached to but not internalized by phagocytic cells . The attached bacteria were quantitated by enzyme-linked immunosorbent assay . Compared with the number of bacteria at zero time (17 bacteria attached per phagocyte) only 10 to 20% of the bacteria remained attached to phagocytic cells after incubation for 30 min at 37 degrees C . The decrease in detected attached bacteria at 37 degrees C was due to internalization of the bacteria by phagocytic cells, since upon disruption of the monolayer, most of the ingested bacteria were recovered, and at 4 degrees C, most of the bacteria remained extracellularly attached . The proposed attachment and ingestion assay is easy to perform, allows the detection of specific attachment of test bacteria, and provides objective quantitation of attached and ingested bacteria . Most importantly, the assay allows testing of ingestion rates of bacteria under many variables on the same day.

Drugs Exp Clin Res, 1988, 14(7), 453 - 60
5-Amino-7-(3-amino-1-pyrrolidinyl)-1-cyclopropyl-6,8-difluoro-1,4- dihydro-4-oxo-3-quinolinecarboxylic acid (PD 124,816) . Synthesis and biological evaluation of a new class of quinolone antibacterials; Domagala JM et al.; A series of 5-amino-1-cyclopropyl-6,8-difluoro-1,4-dihydro-4-oxo-3- quinolinecarboxylic acids with piperazinyl or pyrrolidinyl side-chains appended at C7 were prepared to test the effect of the 5-amino group on the biological and physicochemical properties of these quinolones . The target compounds were synthesized from 2-nitro-3,4,5,6-tetrafluorobenzoic acid and were tested against a variety of Gram-negative and Gram-positive bacteria and the bacterial enzyme DNA gyrase, using standard microtitration techniques . The results are compared to reference quinolones such as ciprofloxacin . The 5-amino derivatives were significantly more potent (2-16 times) than their non-amino analogues . Alkylation or acylation of the 5-amino group reduced potency dramatically . The 5-amino group was neither basic nor nucleophilic . 5-Amino-7-(3-amino-1-pyrrolidinyl)-1-cyclopropyl- 6,8-difluoro-1,4-dihydro-4-oxo-3-quinolinecarboxylic acid (PD 124,816) was selected as the best compound in this study.

Recent Results Cancer Res, 1988, 108, 82 - 8
Selective decontamination of the digestive tract and fungal infection in acute leukemia patients; Gunther I et al.; For prevention of infection we used an SD design including antibacterial (trimethoprim 480 mg/daily, sulfamerazine 720 mg/daily, and polymyxin 0.25 mg/daily) and antifungal (4-6 million IU nystatin/daily) components . We analyzed retrospectively 138 treatment periods in 108 patients . The intensified chemotherapy resulted in severe granulocytopenia below 0.1 x 10(9)/liter over 25.2 days . In 19 patients there was suspicion of major fungal infection; therefore they were given amphotericin B and 5-fluocytosine . Fourteen of them died; major fungal infections were documented in 5 cases . In 18% of all the deceased we found major fungal infections . There was a correlation between fungal infection, the late stages of the hematological malignancy, and the lesions on the oropharyngeal mucosa . However, in terms of the serological and culture findings no correlation appeared to exist between the group with and the group without fungal infection . The SD regime is meant to suppress the Candida cell concentration in the digestive tract but has no influence on Aspergillus in the respiratory tract.

Chemotherapy, 1988, 34(3), 191 - 4
Rate of bactericidal activity for Branhamella catarrhalis of a new macrolide, CP-62,993, compared with that of amoxicillin-clavulanic acid; Yourassowsky E et al.; The rate of bactericidal activity of a new macrolide, CP-62,993, was compared with that of the combination of amoxicillin and clavulanic acid (in the proportion of 4 to 1) on strains of Branhamella catarrhalis beta-lactamase producers . The antibacterial activity of CP-62,993 was bacterostatic at 0.01 micrograms/ml . After a 6-hour period of bacteriostasis a bactericidal activity (3 log10 CFU/ml) was observed for all concentrations from 0.1 to 10 micrograms/ml after 24 h . The bactericidal rate of amoxicillin-clavulanic acid combination was more rapid during the first 6 h at 1 and 10 micrograms/ml . However, the concentration required to kill 99.9% of bacteria within 24 h was 1 microgram/ml . In conclusion, CP-62,993 was a bactericidal antibiotic for B . catarrhalis at a lower concentration . This in vitro study suggests that this macrolide may be of great interest in infections due to the B . catarrhalis beta-lactamase producer.

Nucleic Acids Res, 1987 Dec 23, 15(24), 10495 - 506
Betalactam antibiotics interfere with eukaryotic DNA-replication by inhibiting DNA polymerase alpha; Do UH et al.; Betalactam antibiotics (BLA) are the most widely used antibacterial drugs in practical medicine . Recent experiments suggested that BLA, especially after "aging" in aqueous solutions, have an inhibitory effect on the growth of a variety of cultured human cells by interfering with DNA synthesis (Neftel et al . Cell Biol . Toxicol . 2, 513-521, 1986) . Our initial observation that the replicative DNA polymerase alpha might be the target of the action of betalactam compounds (Hubscher et al . Cell Biol Toxicol . 2, 541-548, 1986) is now substantiated due to the following experimental data: (i) extractable DNA polymerase alpha is greatly reduced in cells that had been treated with BLA; (ii) the relative cellular distribution of thymidine and of its phosphorylated derivatives is not affected by BLA; (iii) BLA inhibit crude and highly purified mammalian DNA polymerase alpha; (iv) the inhibitory effect appears to be of the mixed type with a slight deviation from purely non-competitive behaviour towards the four deoxyribonucleoside triphosphates and; (v) the inhibition is evident in aphidicolin sensitive DNA polymerases from mammalian tissues and in DNA polymerases from DNA viruses such as Herpes simplex and Vaccinia . In sum, the results suggest that one of the most commonly used class of drugs has a target within eukaryotic cells being most likely the replicative DNA polymerase alpha.

Presse Med, 1987 Dec 16, 16(43), 2148 - 52
{Methods for in vitro studies of antibiotic combinations . Indications and limits}; Thabaut A et al.; Several methods are available in the bacteriology laboratory to study the antibacterial effect of antibiotic combinations . With "end point" methods, results are read and interpreted after 18 or 24 hours of incubation . Amongst these methods, gel diffusion is technically easy but gives only qualitative results . Respective concentrations in the interaction zone cannot be evaluated and are unrelated to concentrations obtained in vivo . In liquid medium, the "checker board" method offers the possibility of combining a large number of concentrations . Interpretation may be graphic or mathematical . It is often arbitrary . But above all these methods fail to recognize events which occur during the 18 or 24 hours of incubation . Kinetic methods can be used to evaluate the kinetics of bactericidal action in relation to time and hence to compare the rapidity and degree of the bactericidal action of antibiotics used alone or in combination . However, only a limited number of concentrations can be studied . During the evaluation of a new antibiotic all methods must be tried to determine the possible synergistic or antagonistic effects of combinations regarding bacteria with known different resistance mechanisms . The broad outline thus obtained serves as a prescribing base for combinations . Bactericidal effect should be confirmed by a kinetic method where the concentrations in contact with the bacterial inoculum are selected in relation to presumed concentrations obtained at the site of infection.

J Clin Oncol, 1987 Dec, 5(12), 1985 - 93
Favorable outcome of invasive aspergillosis in patients with acute leukemia; Burch PA et al.; During a 2-year period, 15 of 110 patients (14%) admitted for intensive therapy of acute leukemia associated with prolonged deep granulocytopenia developed documented invasive aspergillosis (IA) . Antemortem diagnosis was accomplished in 14, and 13 of 15 (87%) survived the infection . Because of the high success rate, we reviewed the courses of the 15 patients to assess factors associated with this favorable outcome . Eleven presented with pulmonary IA; early symptoms occurred at a mean 21.6 days of granulocytopenia (less than 100/muL) and included refractory fever in 14 and pulmonary signs or symptoms in 11 . Primary necrotic chest wall lesions associated with Hickman catheters developed in four at a mean 11 days of granulocytopenia, followed by pulmonary involvement . All 15 patients had chest radiographs during granulocytopenia, with 14 (93%) demonstrating pulmonary infiltrates and/or nodules at a mean 20.6 days of aplasia . Nine patients had lung computerized tomography (CT) scans, revealing nodular infiltrates in one patient and a characteristic zone of low attenuation surrounding a mass-like infiltrate in seven other patients, which was found to be diagnostic of IA . Subsequent CT scans performed during and following bone marrow recovery showed progression to cavitation followed by either complete resolution or minimal pulmonary scarring . Eleven patients developed IA during empiric amphotericin B (Amp-B) therapy (0.5 mg/kg/d) for fever refractory to antibacterial antibiotics . Fourteen patients received high-dose Amp-B (1.0 to 1.5 mg/kg/d), which was started within a mean of 2.2 days of first clinical findings; 13 survived . Ten patients received 5-fluorocytosine in addition to high dose amp-B . Survival was similar regardless of presentation, as 91% with primary pulmonary IA and 75% presenting with chest wall lesions survived . All 13 surviving patients had complete granulocyte recovery at a mean 33.8 days . Nephrotoxicity (creatinine greater than 2.0 mg/dL) was observed in seven patients during therapy for IA, but was transient in all seven . We conclude IA can be successfully treated in the deeply granulocytopenic patient provided that it is recognized and treated early, and provided that antifungal therapy is aggressive and is continued until granulocyte recovery occurs.

Jpn J Antibiot, 1987 Dec, 40(12), 1969 - 74
{Clinical studies of norfloxacin on respiratory tract infections in aged people}; Tabeta H et al.; Norfloxacin (NFLX), an oral antibacterial agent of new quinolone derivative, was administered at daily doses of 300-600 mg t.i.d . to 20 aged patients with respiratory tract infections . The results obtained are summarized as follows . 1 . Clinical efficacies were moderate in 6 patients with upper respiratory tract infections, and moderate in 11 patients and fair in 3 patients with lower respiratory tract infections . In the 20 patients, overall clinical efficacies were moderate in 17 patients, hence the efficacy rate was 85% . 2 . Bacteriologically, causative organisms were detected in 10 of the 14 cases with lower respiratory tract infections . In these cases, bacteriological responses were "eradicated" in 9 cases, "decreased" in 1 case and "unknown" in 1 case, the rate of eradication was 90% . 3 . No adverse reactions or abnormal laboratory test values were observed.

Acta Pathol Microbiol Immunol Scand {B}, 1987 Dec, 95(6), 355 - 9
The antibacterial activity of the psychopharmacological agent clopenthixol and its two main metabolites; Mortensen I et al.; The antibacterial effect of the stereo-isomeric compounds cis(Z)- and trans(E)-clopenthixol and the two main metabolites of clopenthixol in man, N-dealkyl-clopenthixol and clopenthixol sulfoxide, was examined in 24 Gram-positive and 37 Gram-negative bacterial strains in vitro . The antibacterial potency of the drugs towards the Gram-positive strains, measured as IC50, was: N-dealkyl-clopenthixol, 6.2 microM (3.7 micrograms/ml), trans(E)-clopenthixol, 16 microM (7.6 micrograms/ml) and cis(Z)-clopenthixol, 37 microM (17.5 micrograms/ml), and clopenthixol sulfoxide was inactive in the investigated area . Against the Gram-negative strains the drugs are less potent . A therapeutic application of these results, especially in the case of trans(E)-clopenthixol, which possesses no neuroleptic activity, requires in vivo testing in an animal model . However, the in vitro model employed might also be useful in the study of such agents and other membrane-active compounds with regard to their interaction with biological membranes.

J Antibiot (Tokyo), 1987 Dec, 40(12), 1657 - 63
New antitumor antibiotic, LL-D05139 beta . Fermentation, isolation, structure determination and biological activities; Lee MD et al.; The LL-D05139 complex, containing LL-D05139 beta and azaserine, was recovered from the fermentation filtrate of Glycomyces harbinensis (NRRL 15337) . A chemically defined medium was developed which favored the production of LL-D05139 beta . Antibiotic LL-D05139 beta was isolated from the fermentation filtrate by adsorption on granular carbon and further purified by chromatography on microcrystalline cellulose . Acid hydrolysis of LL-D05139 beta gave one molar equivalent each of alanine and serine . Both amino acids were found to have the L-configuration by GC analysis on a chiral column and alanine was assigned to be the N-terminal amino acid by Edman degradation . This information coupled with IR, UV, 1H NMR, 13C NMR and MS spectral data allowed us to assign the structure of LL-D05139 beta as alanylazaserine . LL-D05139 beta demonstrated greater antibacterial and biochemical induction assay activities than azaserine . The two drugs showed similar antitumor activities.

Int J Oral Maxillofac Surg, 1987 Dec, 16(6), 695 - 9
Clinical experience with the use of peripheral vasodilator in oral disorders; Sharma JK et al.; Conventional therapies practised in the treatment of asymptomatic neuralgia, oral submucous fibrosis and paraesthesic numbness, are empirical and symptomatic in nature . These are usually prolonged and may be inadequate, impractical with complete or incomplete remissions associated with or without relapses . High dosages of drugs administered for longer duration, are also not infrequently without side-effects . With these problems in view, the clinical use of nylidrin hydrochloride a peripheral vasodilator, was experienced for over 10 years . Irrespective of age, sex and status, 97 cases were randomly extracted from the hospital and oral surgery clinical records . The projected sample included 33 cases of asymptomatic neuralgia, 58 cases of oral submucous fibrosis and 6 cases of numbness . Neuralgia, where mean age was 50 years, was treated with nylidrin hydrochloride, vitamin B-complex and carbamazepine . Oral submucous fibrosis where mean age was 38 years, was treated with nylidrin hydrochloride, vitamins A,E,B-complex, iodine, placental extract, local and systemic corticosteroids and physiotherapy . Paraesthesic numbness, following iatrogenic or accidental trauma to the affected nerve, was treated with nylidrin hydrochloride and B-complex therapy . Peripheral vasodilator administered in all 97 cases, initially contained low divided doses, which steadily were increased or decreased as per individual response . There were reportedly no side-effects, except complaints of flushingly warm skin . Supportive therapy with antibacterials, tranquilizers and analgesics, along with minor dental surgery, were given as and when required . The success rate was 72.16% in total, while individually it varied from 84.85% in neuralgia, 62.07% in oral submucous fibrosis and 100% in numbness.(ABSTRACT TRUNCATED AT 250 WORDS)

J Biol Chem, 1987 Nov 5, 262(31), 14891 - 4
A 25-kDa NH2-terminal fragment carries all the antibacterial activities of the human neutrophil 60-kDa bactericidal/permeability-increasing protein; Ooi CE et al.; We have isolated, after limited proteolysis of the bactericidal/permeability-increasing protein (BPI) of human neutrophils, a 25-kDa fragment that possesses the bactericidal and envelope-altering activities of the 60-kDa parent protein . On a molar basis, the fragment is as potent as holo-human BPI against rough Escherichia coli, is more potent than holo-BPI against more resistant smooth E . coli, and retains the specificity of BPI toward Gram-negative bacteria . NH2-terminal amino acid sequence analysis shows that the fragment is derived from the NH2 terminus of the BPI molecule . These findings suggest that all of the molecular determinants of the antibacterial properties of BPI reside within the NH2-terminal 25-kDa segment, implying a novel structural/functional organization for a cytotoxic protein.

J Antibiot (Tokyo), 1987 Nov, 40(11), 1555 - 62
Synthesis and antibacterial properties of 7-{2-(3-substituted-5-isoxazolyl)-2-methoxyiminoacetamido}cep halospora nic acid derivatives; Sala A et al.; The synthesis of new 2-(3-substituted-5-isoxazolyl)-2-methoxyiminoacetic acids and their condensation derivatives with a suitable cephalosporanic nucleus, is reported . Their antibacterial properties were tested in vivo and in vitro also against beta-lactamase producer microorganisms; particularly the oral bioavailability of some of these new derivatives was studied.

J Antibiot (Tokyo), 1987 Nov, 40(11), 1515 - 9
Xylocandin: a new complex of antifungal peptides . I . Taxonomy, isolation and biological activity; Meyers E et al.; Xylocandin is a complex of novel peptides with potent antifungal activity that is produced by Pseudomonas cepacia ATCC 39277 . The complex was isolated from the fermentation broth by extraction with butanol-methanol, 9:1, followed by collection of the precipitate formed upon concentration of the solvent extract . Purification was effected by chromatography on reversed phase and size exclusion gels followed by TLC on silica gel . These techniques afforded eight components: A1, A2, B1, B2, C1, C2, D1 and D2 . A mixture of the two closely related components, xylocandins A1 and A2, displayed potent anticandidal and antidermatophytic activities in vitro . The activity was diminished by the presence of serum or vaginal washings . No antibacterial activity was demonstrable.

South Med J, 1987 Nov, 80(11), 1407 - 9
Fungal endocarditis complicating treatment of prosthetic valve bacterial endocarditis: value of prophylactic oral nystatin; Gregg CR et al.; We describe two patients in whom fungal endocarditis occurred during antibiotic therapy for prosthetic valve bacterial endocarditis . Successful management of both patients was eventually achieved with antifungal therapy and replacement of the prosthetic valves . These cases and review of the literature suggest that (1) high-dose antibacterial therapy predisposes to fungal endocarditis; (2) during prolonged antibiotic therapy in patients predisposed to endocarditis, clinicians should consider the use of oral nystatin as prophylaxis against fungemia and possible fungal endocarditis; and (3) early replacement of prosthetic valves infected with fungi is indicated because chemotherapy alone is predictably inadequate to effect a cure.

Z Gesamte Inn Med, 1987 Nov 1, 42(21), 614 - 8
{Principles of modern antibiotic therapy in general practice and the clinic}; Siegenthaler W et al.; It is reported on the principles of modern therapy with antibiotics and here above all is referred to the differences in the antibiotic treatment in practice and clinic . Issuing from the infections usually occurring in practice with the spectre of causative agents known in many cases the therapeutic possibilities are discussed also taking into consideration economic points of view . In contrast to this in infections in the clinic, so-called nosocomial diseases, changing situations are present, which need a therapy on the basis of the antibiogramme . In these cases partly also combination therapies for the enlargement of the spectre of action and for the increase of the antibacterial activity are used.

Appl Environ Microbiol, 1987 Nov, 53(11), 2689 - 92
Effects of pentachlorophenol and some of its known and possible metabolites on different species of bacteria; Ruckdeschel G et al.; The antibacterial activity of pentachlorophenol and 35 of its known or possible metabolites against 30 different species of bacteria was tested . In comparison with pentachlorophenol, no increase of inhibitory activity was found for any of the chlorinated anisoles tested (except for pentachloroanisole against Streptomyces spp.), 2-chlorophenol, 2,6-dichlorophenol, 2,3,6- and 2,4,6-trichlorophenol, 2,3,5,6-tetrachlorophenol, tetrachloro-1,4- and -1,3-benzenediol (except for the 1,3-isomer against Streptomyces spp.), tetrachloro-1,3-dimethoxybenzene, and tetrachloro-1,3-benzenediol diacetate . Two chlorophenols, five dichlorophenols, four trichlorophenols, two tetrachlorophenols, and tetrachloro-1,2-benzenediol were more active than pentachlorophenol against some, but not all, of the strains tested.

Rev Med Interne, 1987 Nov-Dec, 8(5), 527 - 32
{New aspects of macrolides: contribution of roxithromycin}; Bertrand A et al.; Roxithromycin (RU 28965) is a new semi-synthetic derivative of erythromycin . Its antibacterial activity is of the same order as that of other macrolides, although its MIC's against Legionella pneumophila are lower . In double-blind comparative studies there was no significant difference in therapeutic effectiveness between roxithromycin and the reference antibiotics tested . However, this new macrolide exhibits exceptional pharmacological properties (prolonged half-life, excellent tissue penetration and intracellular activity), and it is very well tolerated both clinically and biochemically.

J Antimicrob Chemother, 1987 Nov, 20 Suppl B, 81 - 8
Comparative pharmacokinetics of macrolides; Nilsen OG; The search for erythromycin derivatives with improved antibacterial and/or pharmacokinetic properties, has led to the synthesis of several new agents . Roxithromycin, an ether oxime derivative of erythromycin, is one of the more promising . The main differences between erythromycin and roxithromycin are their kinetics, roxithromycin giving higher serum concentrations than erythromycin at equimolar oral doses . Its elimination half-life is also longer, about 12 h compared to 2-3 h for erythromycin . As their tissue distributions and antibiotic profiles are similar, roxithromycin can be administered in lower daily doses and at less frequent intervals . A suitable dosage regimen for roxithromycin seems to be 150 mg every 12 h . From a pharmacokinetic point of view, daily dosing with roxithromycin would be equivalent to the administration of erythromycin every 6 h.

J Biomed Mater Res, 1987 Nov, 21(11), 1281 - 300
Newly made antibacterial braided nylon sutures . I . In vitro qualitative and in vivo preliminary biocompatibility study; Chu CC et al.; A new type of braided nylon thread with a silver compound coating was made for the purpose of designing a biocidal suture material . The study used standard bacterial culture techniques to evaluate the antibacterial property of the new Ag-coated nylon thread . Seven types of bacterial species were tested; S . aureus, E . coli, P . aeruginosa, K . pneumoniae, S . dysenteriae, S . maruslens, and P . mirabilis . The commercial size 2/0 Nurolon suture from Ethicon served as the control . A weak direct current ranging from 0.4-400 microA was applied to the specimens to examine whether the biocidal property of silver could be enhanced by current . The antibacterial property was evaluated by the width and sterility of the clear zone in the bacterial culture plates . It was found that the new nylon thread exhibited very good to moderate bactericidal property toward these seven bacterial species . P . aeruginosa was the most sensitive species, while P . mirabilis was the least sensitive one . Application of direct current through the Ag-coated specimens positively enhanced their antibacterial property and the degree of enhancement depended on the direct current level . The material also exhibited an antibacterial property toward well-established bacterial colonies, but the effect was less strong than the case when direct current was applied simultaneously with incubation . Silver ions released from the coated nylon thread were responsible for the observed antibacterial property; and the application of a weak direct current to the material enhanced this effect . A preliminary biocompatibility study of this new material in rat gluteal muscle indicated that the new material caused less inflammatory reaction than the control Nurolon suture up to 60 days after implantation.

J Med Chem, 1987 Nov, 30(11), 1998 - 2004
2,4-Diamino-5-benzylpyrimidines as antibacterial agents . 8 . The 3,4,5-triethyl isostere of trimethoprim . A study of specificity; Roth B et al.; 3,4,5-Triethylacetophenone was synthesized in 60% yield by a Friedel-Crafts reaction from 4-ethylacetophenone and converted to 2,4-diamino-5-(3,4,5-triethylbenzyl)pyrimidine (2), a trimethoprim (1) isostere, by standard techniques . This compound is more lipophilic than 1 by three log units (log P, octanol/water) . Compound 2 was approximately equipotent with 1 in inhibiting Escherichia coli dihydrofolate reductase (DHFR), 2-fold more potent against P . berghei and N . gonorrhoeae DHFR, and 10 and 25 times better an inhibitor of rat and chicken liver DHFR, respectively . Although the 3,4-dimethoxy analogue 19 was 10-fold less inhibitory to E . coli DHFR than 1, it was 3-4 times more potent on the vertebrate isozymes, whereas the diethyl congener 10 followed 19 in its E . coli DHFR binding but was less active on rat and chicken DHFR . Therefore, a significant portion of the selectivity of 1 for bacterial, as opposed to vertebrate, DHFR, involves the methoxy functions . An analysis of the X-ray data on 1 and 2 complexed with chicken DHFR, coupled with kinetic data, led to the conclusion that the difference in binding energies of the methoxy and ethyl compounds probably involve desolvation factors, as well as direct energies of interaction with protein atoms . Thus, one cannot invoke lipophilicity or shape alone in explaining the relationship in properties of 1 and 2.

Microb Pathog, 1987 Nov, 3(5), 377 - 86
Purified human and recombinant murine interleukin-1 alpha induced accumulation of inflammatory peritoneal neutrophils and mononuclear phagocytes: possible contributions to antibacterial resistance; Czuprynski CJ et al.; Interleukin-1 (IL-1) mediates a number of proinflammatory biological responses that are thought to contribute to antibacterial resistance . In the present study we examined the ability of IL-1 to recruit inflammatory neutrophils and mononuclear phagocytes in vivo; a function that has been reported to be closely related to antibacterial resistance . Intraperitoneal injection of small amounts (1-10 LAF units) of purified human or recombinant murine IL-1 alpha (rIL-alpha) resulted in an increased influx of inflammatory neutrophils into the peritoneal cavity that peaked at 4-14 h after IL-1 injection . A small but consistent increase in peritoneal macrophages also was observed at 72 h after rIL-1 alpha injection . The ability of rIL-1 alpha to induce neutrophil accumulation was uninfluenced by polymyxin B, was sensitive to heat treatment (100 degrees C for 1 h), and was observed after i.p . injection into LPS-nonresponsive C3H/HeJ mice . These three lines of evidence suggested that contaminating LPS did not contribute substantially to rIL-1 alpha induced accumulation of neutrophils . Treatment of mice with indomethacin or nordihydroguaiaretic acid did not abrogate rIL-1 alpha induced neutrophil accumulation . Mice injected i.p . with increasing amounts of rIL-1 alpha demonstrated a corresponding enhancement of their resistance to an i.p . L . monocytogenes challenge 4 h later, thus suggesting that IL-1 mediated inflammatory phagocyte accumulation may contribute in part to nonspecific antibacterial resistance.

Biomed Environ Mass Spectrom, 1987 Nov, 14(11), 669 - 73
Plasma desorption mass spectrometry coupled with conventional peptide sequencing techniques; Craig AG et al.; The mass of intact and enzymatically derived fragments of cecropin B, an antibacterial protein from the Chinese oak silk moth, Antherea pernyi, have been determined by 252Cf plasma desorption time-of-flight mass spectrometry . As a result, the carboxy terminal amino acid sequence of the protein was established.

J Antibiot (Tokyo), 1987 Nov, 40(11), 1572 - 87
Synthesis and biological activity of some esters of the N-acetylglucosaminyl aglycone and of the aglycone of teicoplanin; Malabarba A et al.; A series of ester derivatives of teicoplanin-N-acetylglucosaminyl aglycone (T-A3-2) and deglucoteicoplanin was prepared starting from teicoplanin and from the corresponding deglycosylation compounds . The modification of the ionic and lipophilic character of the parent antibiotic strongly influences the spectrum of antibacterial activity in vitro.

Antimicrob Agents Chemother, 1987 Nov, 31(11), 1861 - 3
Antagonism of wild-type and resistant Escherichia coli and its DNA gyrase by the tricyclic 4-quinolone analogs ofloxacin and S-25930 stereoisomers; Wolfson JS et al.; The mechanism of action of the quinolone analogs ofloxacin and S-25930, which are unusual because of the presence of a third ring with an asymmetric carbon, was studied . Drug-resistant strains of Escherichia coli were selected by serial passage in the presence of ofloxacin, and a mutation was mapped near the gyrA gene of DNA gyrase . DNA gyrase containing the A subunit purified from this strain as compared with the isogenic wild-type strain exhibited increased resistance to ofloxacin, proving that the mutation was located in the gyrA gene . For S-25930, the S stereoisomer was more potent than the R isomer in inhibiting wild-type E . coli and DNA gyrase containing an A subunit isolated from this strain . Both isomers had decreased potency against the isogenic ofloxacin-resistant (gyrA) strain and its purified enzyme, but the S isomer remained more potent than the R isomer . These studies, using a combined genetic and biochemical approach, demonstrate (i) that DNA gyrase is a target of the tricyclics ofloxacin and S-25930, (ii) that serial exposure to ofloxacin can select resistance to tricyclic quinolone agents by mutation in the gyrA gene, and (iii) that the more potent antibacterial activity of S relative to R S-25930 correlates with increased activity against DNA gyrase for both wild-type and ofloxacin-resistant (gyrA) isogenic strains.

Antimicrob Agents Chemother, 1987 Nov, 31(11), 1831 - 40
Computer automated structure evaluation of quinolone antibacterial agents; Klopman G et al.; The Computer Automated Structure Evaluation (CASE) program was used to study a series of quinolone antibacterial agents for which experimental data pertaining to DNA gyrase inhibition as well as MICs against several strains of gram-positive and gram-negative bacteria are available . The result of the analysis was the automatic generation of molecular fragments relevant to the respective biological endpoints . The potential significance of these major activating-inactivating fragments to the biological activity is discussed.

Paraplegia, 1987 Oct, 25(5), 381 - 5
Urological problems in the management of quadriplegic women; Lindan R et al.; During the past 25 years enormous progress has been made in the management of the neuropathic bladder, largely as a result of the adoption of intermittent catheterisation, together with improvements in catheter-related techniques, and the judicious use of antibacterial drugs and sphincter surgery . A few quadriplegic women can be trained to do self-intermittent catheterisation, using a special technique . For the majority of these women, however, there is no practical alternative at present to indwelling catheters . Bladder spasms resulting from the mechanical stimulation of the catheter and/or repeated infections may be difficult to control, and illustrative cases demonstrating some problems encountered are presented . There is an obvious need for an external collecting device for these women . The development in the field of such devices are presented and evaluated.

Acta Pathol Microbiol Immunol Scand {B}, 1987 Oct, 95(5), 293 - 6
Antibiotics and human monocyte function . I . Chemotaxis; Nielsen H; The influence of thirteen commonly used antibacterial drugs on the chemotactic responsiveness of human blood monocytes in vitro was investigated . Tetracyklin, trimethoprim and fusidic acid at high concentrations produced a significant inhibition of the monocyte response, whereas normal therapeutic concentrations produced insignificant inhibition . Benzylpenicillin, ampicillin, tobramycin, chloramphenicol, metronidazole, rifampicin, clindamycin, sulfametoxazole, cefotaxime and ofloxacin did not alter monocyte migration . From these observations it can be expected that at normal dosages none of the tested drugs will affect monocyte chemotaxis in vivo.

Dis Colon Rectum, 1987 Oct, 30(10), 743 - 6
The inadequacy of published random control trials of antibacterial prophylaxis in colorectal surgery; Evans M et al.; Fifty-six papers published between 1979 and 1986 that tested regimens of antibacterial bowel preparation before elective colorectal operations were studied using a numerical score devised for assessing publications of random control clinical trials . A maximum score of 100 was allotted: 50 for 15 aspects of design, 30 for ten aspects of analysis, and 20 for eight aspects of presentation . The 56 papers scored from 33 to 89, (mean, 61.6, standard deviation, 11.9) . Only 13 (23 percent) reached a score of more than 70 . The most frequent errors in design were the use of placebos in the control group (27 percent) and faulty methods of randomization (36 percent) . Errors in analysis resulted in penalization of more papers than any other aspect; these included the almost universal omission of confidence limits, confusion of exclusions and withdrawals (46 percent), not recording the fate of withdrawals (80 percent) and incorrect use of statistical tests (55 percent) . Ten papers reported results showing important clinical differences that did not achieve statistical significance, but only two mentioned the Type II error . Defects in presentation were less frequently encountered; the most common were inaccessibility of raw data (66 percent), lack of sufficient information to allow replication of methods (43 percent), and the drawing of firm conclusions from shaky data (50 percent) . It was particularly disappointing that no evidence of improvement in the standard of these reports over the seven years studied was found.

Chest, 1987 Oct, 92(4), 663 - 9
New synthetic quinolone antibacterial agents and serum concentration of theophylline; Niki Y et al.; The effect of pipemidic acid and five new synthetic antibacterial agents--norfloxacin, enoxacin, ofloxacin, ciprofloxacin, and pefloxacin--on the serum level of theophylline was studied in healthy male adult volunteers after concomitant oral administration of these agents with a slow release preparation of theophylline . The results indicated that enoxacin, ciprofloxacin, and pipemidic acid might decrease the clearance of theophylline in the liver, and the attention should be paid in clinical use when enoxacin or pipemidic acid is coadministered with theophylline.

Int Surg, 1987 Oct-Dec, 72(4), 243 - 6
Septisol antiseptic foam: a sensible alternative to the conventional surgical scrub; Rubio PA; Over a recent 8-year period, Septisol Foam (0.23% hexachlorophene in a 46% ethyl alcohol base) alone was used to prepare the hands and forearms of the author's surgical team . In 3480 cases, only 11 postoperative infections were encountered, for an incidence of 0.3% . All 11 infections involved patients who underwent gastrointestinal surgery and/or who had high-risk factors such as cancer, hypertension, diabetes mellitus, perforated appendix, emergency surgery, age over 65 years, and foreign bodies in the form of hemodialysis access shunts . Septisol Foam is an effective bacteriostatic agent that minimizes the risk of dermatitis and offers sufficient antibacterial protection without supplementary handwashing . When used according to the method described here, the foam eliminates the need for scrub brushes and reduces the total scrub time to approximately 2 minutes in each case . In addition to being safe, effective, and easy to use, this method results in a marked decrease in water consumption and considerable monetary savings.

J Appl Bacteriol, 1987 Oct, 63(4), 293 - 8
The antibacterial activity of alamethicins and zervamicins; Jen WC et al.; Consistent results were obtained in biological assays of alamethicins on agar gels only when the antibiotics were allowed to diffuse under strictly defined conditions of temperature and time before inoculation . In liquid culture obligatory anaerobic rumen bacteria were sensitive to these antibiotics and in certain cases their ability to produce volatile fatty acids was reduced . Among the bacteria examined there was a 1000-fold difference in their sensitivity . Modifications of the structure of the peptaibol, e.g . substitution of an alanine residue for a 2-methylalanine residue resulted in ca two-fold changes in activity.

Antimicrob Agents Chemother, 1987 Oct, 31(10), 1632 - 9
Value of antibiotic levels in serum and cardiac vegetations for predicting antibacterial effect of ceftriaxone in experimental Escherichia coli endocarditis; Joly V et al.; In a rabbit model of Escherichia coli endocarditis, we studied the penetration into infected vegetations and the antibacterial effect of ceftriaxone . Ceftriaxone was given at different dosages, alone or with an interfering agent, diclofenac, a nonsteroidal anti-inflammatory drug, to determine the predictive value of the antibiotic levels in serum or infected vegetations on the antibacterial efficacy . Diclofenac increased the serum terminal half-life of ceftriaxone and increased its extravascular diffusion in tissue cage fluid, as well as in infected vegetations, allowing us to obtain various antibiotic concentrations in the infected site . Two hours after the fourth injection, around the time of peak level in serum, we observed a linear relationship between (i) serum and local antibiotic levels in vegetations, (ii) local antibiotic levels in a range of 142 to 600 X MBC and bacterial titer (log10 CFU/g) in vegetations, and (iii) serum antibiotic levels in a range of 800 to 1,400X MBC and bacterial titer in vegetations . In vivo, antibacterial effect was obtained only with high antibiotic levels in vegetations (greater than or equal to 220X MBC) . This was confirmed by incubating vegetations sampled from infected animals in rabbit serum containing ceftriaxone (ex vivo experiment) . Given once daily at a therapeutic dosage (30 mg/kg) for 4 days, ceftriaxone exhibited good efficacy (log10 CFU/g of vegetation = 2.41 +/- 2.7 versus 7.41 +/- 0.92 in control animals) and prevented regrowth of bacteria until 24 h after the last injection . We concluded that (i) provided the dose is sufficient, a long-acting cephalosporin can prove effective in severe gram-negative infections even when given infrequently, and (ii) serum antibiotic levels around the peak value, reflecting high effective local levels, could predict the therapeutic efficacy and represent a simple test to monitor the clinical course of a severe infectious process.

J Bacteriol, 1987 Oct, 169(10), 4845 - 7
Dimethylthetin can substitute for glycine betaine as an osmoprotectant molecule for Escherichia coli; Chambers ST et al.; Glycine betaine is believed to be the most active naturally occurring osmoprotectant molecule for Escherichia coli and other bacteria . It is a dipolar ion possessing a quaternary ammonimum group and a carboxylic acid group . To examine the molecular requirements for osmoprotective activity, dimethylthetin was compared with glycine betaine . Dimethylthetin is identical to glycine betaine except for substitution of dimethyl sulfonium for the quaternary nitrogen group . Dimethylthetin was found to be about equally as effective as glycine betaine in permitting E . coli to grow in hypertonic NaCl, and both compounds were recovered almost completely from bacterial cells grown in the presence of hypertonic NaCl . 3-Dimethylsulfonioproprionate, an analog of dimethylthetin observed in marine algae, and 3-Dimethylsulfonio-2-methylproprionate were found to be less active . Dimethylthetin may prove useful as a molecular probe to study betaine metabolism and as a model for the development of antibacterial agents.

Eur J Clin Microbiol, 1987 Oct, 6(5), 584 - 6
In vitro activity of four fluoroquinolones against eighty-six isolates of mycobacteria; Texier-Maugein J et al.; The in vitro activity of pefloxacin, norfloxacin, ofloxacin and ciprofloxacin against 86 strains of mycobacteria was evaluated by broth dilution . While Mycobacterium avium, Mycobacterium scrofulaceum and Mycobacterium chelonae were resistant to all four antibacterials, the susceptibility of the other species, Mycobacterium tuberculosis, Mycobacterium kansasii, Mycobacterium xenopi and Mycobacterium fortuitum, depended on the antibiotic . Ofloxacin and ciprofloxacin (MIC90: 0.5 - 2 mg/l) were more active than pefloxacin and norfloxacin (MIC90: 2 - 16 mg/l).

Immunopharmacology, 1987 Oct-Nov, 14(2), 101 - 6
Effect of erythromycin on the immune response and interferon production; Biglino A et al.; The influence of erythromycin on some aspects of humoral and cell-mediated immunity has been examined employing human as well as murine models, both in vivo and in vitro . No significant differences in antibody synthesis, alpha- and gamma-interferon yield, cutaneous delayed hypersensitivity or lymphocyte blastogenic response to mitogens have been detected between erythromycin-treated subjects and controls . Similarly, in vitro tests on interferon production and blastogenic response to mitogens showed no significant differences when performed with and without erythromycin . Therefore, in contrast with many other antibacterial drugs, erythromycin seems to be devoid of any adverse effects on the immune system.

Am J Med, 1987 Sep 28, 83(3B), 125 - 7
Antibacterial activity of sucralfate in human gastric juice; Tryba M et al.; A series of experiments was conducted to determine the rate of bacterial growth in human gastric juice at various pH values in relation to the addition of sucralfate and antacid . Whereas the addition of antacid resulted in bacterial growth in gastric juice, sucralfate showed an antibacterial effect . This may account for the decreased rate of pneumonia among intensive-care patients who are receiving artificial ventilation and being treated with sucralfate for the prevention of stress-induced gastrointestinal bleeding compared with the rate in patients receiving conventional prophylaxis with histamine (H2)-antagonists or antacids.

Biochem Biophys Res Commun, 1987 Sep 15, 147(2), 801 - 8
Uncoupling of mitochondrial oxidative phosphorylation by hexetidine; D'Arcangelo G et al.; To gain further insight into the biochemical properties of the antibacterial hexetidine, isolated rat liver mitochondria were added with this drug and investigation made of certain features related to mitochondrial bioenergetics . Hexetidine was found to cause oxidation of intramitochondrial pyridine nucleotides and stimulate the rate of oxygen uptake caused by respiratory substrates involving three, two and one site(s) of phosphorylation . Reversal of oxygen uptake inhibition by oligomycin was also determined . By investigating hexetidine effect on oxidative phosphorylation, hexetidine was found both to inhibit the rate of ATP synthesis and to cause ATP hydrolysis . Likewise, hexetidine capability to produce acidification of extramitochondrial medium and to collapse delta psi was also observed . The reported findings show that hexetidine exhibits uncoupling properties.

Nature, 1987 Sep 10-16, 329(6135), 162 - 4
Antibacterial agents specifically inhibiting lipopolysaccharide synthesis; Goldman R et al.; The spread of antibiotic resistance in Gram-negative bacteria has sustained a continuing search for new agents with antibacterial activity against this important class of bacterial pathogen . Because the biosynthesis of lipopolysaccharide (LPS) is unique to Gram-negative bacteria and required by them for growth and virulence, attempts have been made to discover or design antibacterial agents acting at this site; however, no such agents have so far been developed . We now present definitive experimental data documenting design of the first member of the class of antibacterial compounds which specifically inhibit LPS synthesis . The target enzyme is 3-deoxy-D-manno-octulosonate cytidylytransferase (CMP-KDO synthetase), a cytoplasmic enzyme which activates 3-deoxy-D-manno-octulosonate (KDO) for incorporation into LPS . A specific inhibitor of CMP-KDO synthetase, alpha-C-(1,5-anhydro-7-amino-2,7-dideoxy-D-manno-heptopyranosyl)-carboxy late was designed using results of our studies of the purified enzyme . LPS synthesis ceased and lipid A precursor accumulated, causing growth stasis and perturbation of outer membrane structure and function, following delivery of the inhibitor to the intracellular target by a peptide carrier . Antibacterial action required an intact oligopeptide permease system and specific intracellular aminopeptidase activity to release inhibitor from the peptide prodrug.

Biochemistry, 1987 Sep 8, 26(18), 5878 - 84
Inactivation of alanine racemase by beta-chloro-L-alanine released enzymatically from amino acid and peptide C10-esters of deacetylcephalothin; Mobashery S et al.; The reactions of a set of amino acid and peptidyl C10-esters of deacetylcephalothin (1-5) have been examined with purified enzymes in vitro . Each of the compounds examined is a substrate for the Escherichia coli TEM-2 beta-lactamase, and enzyme-catalyzed hydrolysis of the lactam bond gives release of an amino acid or a peptidyl fragment from a cephem nucleus . 7 beta-(2-Thienylacetamido)-3-{{(beta-chloro-L-alanyl)oxy}methyl}-3- cephem-4-carboxylate (4) gives time-dependent inactivation of E . coli JSR-O alanine racemase in a process that requires beta-lactamase for the initial liberation of beta-chloro-L-alanine from the cephalosporin . Alanine racemase is similarly inactivated by 7 beta-(2-thienylacetamido)-3-{{{(beta-chloro-L-alanyl)-beta-chloro- L- alanyl}oxy}methyl}-3-cephem-4-carboxylate (1), but this inhibition requires the sequential action of both beta-lactamase and alanine aminopeptidase . Analysis of the enzymatic transformations of 7 beta-(2-thienylacetamido)-3-{{{(beta-chloro-L-alanyl)-L- alanyl}oxy}methyl}-3-cephem-4-carboxylate (3), monitored by high-field 1H NMR, reveals that (1) beta-lactamase releases the dipeptide beta-chloro-L-alanyl-L-alanine from 3 and (2) leucine aminopeptidase effects stoichiometric hydrolysis of the dipeptide to beta-chloro-L-alanine and L-alanine . These biochemical findings are discussed with reference to the mechanism of antibacterial action of 1 against beta-lactamase-producing, penicillin-resistant microorganisms {Mobashery, S., Lerner, S . A., & Johnston, M . (1986) J . Am . Chem . Soc . 108, 1685}.

J Antibiot (Tokyo), 1987 Sep, 40(9), 1325 - 30
Synthetic cephalosporins . II . The synthesis and oral activity of 7-{R-2-amino-2-(3-chloro-4-hydroxyphenyl)acetamido}-3-methylthio-3- cephem-4-carboxylic acid and related compounds; Sakagami K et al.; A series of 3-methylthio-3-cephem-4-carboxylic acids were prepared to test their antibacterial activities, and 7-{R-2-amino-2-(3-chloro-4-hydroxyphenyl)acetamido}-3-methylthio-3-ce phe m-4- carboxylic acid was found to be a new orally active antibiotic.

J Pediatr Surg, 1987 Sep, 22(9), 869 - 72
Perioperative prophylaxis with sulbactam and ampicillin compared with metronidazole and cefotaxime in the prevention of wound infection in children undergoing appendectomy; Foster MC et al.; Sulbactam is a beta-lactamase inhibitor, which when administered with ampicillin, increases the latter agents antibacterial activity against beta-lactamase producing organisms . One hundred children between the ages of 5 and 14 undergoing emergency appendectomy were entered into a prospective randomized trial comparing sulbactam and ampicillin (SA) with metronidazole and cefotaxime (MC) as prophylaxis against postoperative wound infection . Patients in whom the appendix was perforated or gangrenous received a 72-hour course of antibiotics, others received a single dose only . The overall wound infection rate was 8% (14% in patients with perforation or gangrene and 4% in those without) . There was no difference in infection rate between the two antibiotic groups; there were three wound infections and one subphrenic abscess in patients receiving SA and four wound infections in patients receiving MC . SA, therefore, appears to be a suitable antibiotic combination for use as prophylaxis in appendicitis in children.

Antibiot Med Biotekhnol, 1987 Sep, 32(9), 668 - 71
{Mass spectrophotometric study of the antibiotic granaticin}; Kliuev NA et al.; A culture of Streptomyces sp . producing a substance with antibacterial and antitumor activity was isolated from a soil sample collected in the Gorno-Altai Autonomous Province . By its UV, NMR and mass spectra the antibiotic was identified as granaticin . Mass spectral disintegration of granaticin was studied in detail: mass spectra of electron impulse (including that of high performance), field desorption, chemical ionization of positive and negative ions . Correlation relationship between directions of fragmentation of the molecular and basic moiety ions and fragments of the antibiotic structure was derived . Specific peaks of the ions providing mass spectrometric identification of the antibiotic in various natural mixtures were detected.

Am J Otol, 1987 Sep, 8(5), 385 - 9
Functional morphology of the tubotympanum related to otitis media: a review; Lim DJ et al.; One of the important functions of the tubotympanum is to protect the middle ear from invading organisms . The host develops a number of strategies for this function (e.g., mucociliary protection, antibacterial secretory products, immunodefense, and phagocytosis) . The bacteria also develop their strategy to evade the host protection by enhancing adherence to the mucosal surfaces, impairing mucociliary function, and evading phagocytosis.

Antimicrob Agents Chemother, 1987 Sep, 31(9), 1375 - 8
Cefotaxime stability during in vitro microbiological testing; Marchbanks CR et al.; Cefotaxime is a broad-spectrum cephalosporin which is metabolized or degraded to less active or inactive metabolites by serum esterases, elevated temperatures, or a pH outside of its stability range . Cefotaxime instability during in vitro microbiological susceptibility tests may lead to an underestimation of the antibacterial activity of the compound . Cefotaxime and desacetylcefotaxime solutions were studied under MIC and serum inhibitory titer testing conditions . Cefotaxime concentrations, as measured by high-performance liquid chromatography, decreased 20 to 30% over the incubation period in various systems tested; the greatest decline occurred in systems containing serum in the media . Changes in the results of microbiological susceptibility tests interpreted after 6 and 18 h of incubation were consistent with changes observed in the high-performance liquid chromatography analysis . This study demonstrates cefotaxime instability under conditions of in vitro microbiological testing.

Am J Trop Med Hyg, 1987 Sep, 37(2), 370 - 5
In vitro cultivation of third stage larvae of Wuchereria bancrofti to the fourth stage; Franke ED et al.; Third stage larvae of Wuchereria bancrofti obtained from laboratory-infected mosquitoes grew and molted to the fourth stage in vitro . The culture medium which supported the best growth and development consisted of a 1:1 mixture (v/v) of two commercially available cell culture media, NCTC 135 and Iscove's modified Dulbecco's medium supplemented with 10% human serum or plasma and an antibacterial/antimycotic mixture . Cultures were incubated at 37 degrees C in an atmosphere of either 5% or 8% CO2 in air . After 35 days of culture, 65% to 100% of the larvae were fourth stage . They were motile and in excellent morphological condition with development of the reproductive system in males and females . This culture system will provide an important tool for biochemical and immunological studies.

Blood, 1987 Sep, 70(3), 779 - 85
Long lasting IgG subclass and antibacterial polysaccharide antibody deficiency after allogeneic bone marrow transplantation; Aucouturier P et al.; Serum IgG subclasses were measured by a competitive indirect immunoassay with monoclonal antibodies in 31 leukemic patients before and after bone marrow transplantation . Antibodies to Hemophilus influenzae type b (Hib) capsular polysaccharide were determined in 28 cases . Abnormally low or borderline subclass (mostly IgG2 and IgG4) levels were found late after transplant in 23 infected and noninfected patients . These levels persisted for as long as 25 months, in association with low or borderline IgA levels in 78% of the cases . IgG2, IgG4, and IgA often showed a parallel evolution, whereas IgG1, IgG3, and IgM often varied together in the opposite way . Class but not subclass deficiencies were more frequent in patients with graft-v-host disease (GVHD) . Subclass abnormalities predominated in infected patients, with mean levels correlating with the severity of infections; however, the abnormalities are not clearly predictive of infections in individual cases . Most patients with Hib pneumonia showed virtually no IgG antibody response to Hib, and one-half of the patients had a moderate IgM and IgA response . In the whole series, many sera collected greater than 1 year after graft contained very low or undetectable antibodies . Correlation between anti-Hib antibody and IgG2 levels was significant but weak because of discrepancies that were only partially explained by the subclass distribution of the antibodies.

Clin Chest Med, 1987 Sep, 8(3), 359 - 72
The relationship between malnutrition and lung infections; Martin TR; In summary, the association between malnutrition and infections, including respiratory infections, seems clear from consistent experience in developing nations . Young children are at the greatest risk, both of severe malnutrition and complicating infections . The cell-mediated immune system is the most affected by protein-calorie malnutrition, but antibody responses are also affected and complement levels are low . Infections with organisms handled by cell-mediated immunity would be the most predictable, but the immunoglobulin responses that are important for opsonization of invading microorganisms may also be impaired . The experience in developing nations has been extrapolated to patients in US hospitals, because hospitalized patients often have one or more abnormal nutritional parameters . However, severe malnutrition of the sort found in children in developing nations is uncommon in hospitalized patients, and the effects of malnutrition on host defenses in adults are likely to be less severe than in children . Whether the degrees of malnutrition that have been described in hospitalized patients produce clinically significant effects on antibacterial defenses in the lungs of adults remains uncertain . Despite the intuitive importance of nutritional support, and the repeated observation that nutritional parameters improve with nutritional support, a number of controlled trials have failed to show a clear improvement in patient outcome with aggressive nutritional therapy, including parenteral hyperalimentation . The results of these studies, together with the risks involved in parenteral alimentation have led some to suggest that "the emperor has no clothes," and that aggressive nutritional support is not worthwhile for most patients . The major problem in interpreting the data is the lack of clear clinical endpoints, and this may obscure potentially important responses to nutritional therapy . Nutritional status is only one of many interacting variables that may affect clinical outcome, particularly in patients in critical care units . Survival usually depends on many factors, particularly the status of major organ systems independent of nutrition, so that survival as an endpoint for nutritional studies is likely to be too insensitive . Prospective studies of the incidence and significance of infections, particularly pneumonia, in malnourished patients and the effects of nutritional therapy are lacking . At present, the prudent approach is to treat infections aggressively in malnourished patients, with antibiotics and drainage if necessary, and to provide nutritional supplementation in all patients via the gut as long as possible.(ABSTRACT TRUNCATED AT 400 WORDS)

J Surg Res, 1987 Sep, 43(3), 239 - 45
The effects of in vivo antibiotics on neutrophil (PMN) activity in rabbits with peritonitis; Sheng FC et al.; Antibiotics play an important role in helping the host fight infection; however, the direct cellular effect of antibiotics on polymorphonuclear cells remains undefined . Adherence, chemotaxis, phagocytosis, and superoxide anion production are important steps in the cascade of events initiated by the polymorphonucleocyte in bacterial killing . Previous studies have shown inhibition as well as stimulation of neutrophil antibacterial therapy by antibiotics . Peritoneal and blood polymorphonuclear neutrophils (PMN) respond differently to peritonitis and to external agents . The purpose of this study was to investigate the effects of in vivo clindamycin and netilmicin on infected rabbit peritoneal and blood polymorphonuclear adhesiveness, phagocytosis, chemotaxis, and superoxide anion production . Peritoneal and blood PMNs were obtained from rabbits which had undergone appendiceal devascularization 18 hr earlier: antibiotics were administered intramuscularly 1 hr prior to appendectomy and every 8 hr postoperatively for 5 days; these PMNs were compared to infected rabbits which did not receive antibiotics . Clindamycin and netilmicin in vivo cause significant inhibition of phagocytosis, peritoneal adhesiveness, and, when used in combination, blood adhesiveness and peritoneal superoxide anion production . No effects were seen on chemotaxis . Based on this data we conclude that antibiotics, while vitally important in fighting infections, may in and of themselves be agents of immunosuppression at the cellular level.

Drug Metab Dispos, 1987 Sep-Oct, 15(5), 676 - 81
The development of hepatic drug-metabolizing enzyme activity in the neonatal calf and its effect on drug disposition; Shoaf SE et al.; Mixed function oxidase and UDP-glucuronyltransferase activity was measured in liver microsomal preparations from 1-, 7-, and 42-day-old, male, Holstein calves . Liver samples were obtained by a surgical biopsy procedure that allowed for multiple samples to be taken from a single individual . Microsomal protein content doubled between 7 and 42 days of age and reached adult levels during this time . Cytochrome P-450 content increased 2-fold during the first week and remained constant thereafter . NADPH-cytochrome c reductase activity doubled during the first week, but then returned to its initial level by 42 days of age . UDP-glucuronyltransferase activity was well developed at 1 day of age and reached adult levels by 7 days of age . Mixed function oxidase activity was less well developed; activities at 1 day of age were only 17-50% of those at 42 days of age for O-deethylation, O- and N-demethylation, and aryl hydrocarbon hydroxylation . Development of hepatic drug-metabolizing activity was discussed in relation to the age-related increase in the rate of elimination of the antibacterial compound trimethoprim.

J Oral Pathol, 1987 Sep, 16(8), 417 - 20
The salivary peroxidase system: thermodynamic, kinetic and antibacterial properties; Pruitt KM; Enzymes are specific catalysts which optimize the rates of reactions vital to living organisms . If the oxidation of thiocyanate (which occurs, in vivo, in human saliva and salivary glands) is a vital reaction for the maintenance of oral health, then the enzyme (salivary peroxidase), which catalyzes this reaction, should function optimally under in vivo conditions . Studies have shown that salivary peroxidase maintains the SCN- oxidation reaction in an apparent state of dynamic equilibrium, that the kinetic properties of the enzyme provide optimum rates of reaction under in vivo conditions, and that the antibacterial properties of the products of the reaction are optimum under those conditions where unlimited bacterial metabolism provides the greatest threat to host tissues . The evidence indicates that the salivary peroxidase enzyme has evolved in such a way as to maximize its protective value in the oral cavity.

Chemioterapia, 1987 Aug, 6(4), 299 - 305
Relationships between chemical structure and adverse effects of antibacterial and antifungal agents; Neuman M; Chemical structure and adverse effects are presented, including the side chains responsible for platelet inhibitory effects, hypoprothrombinemic effects, the disulfiram effect of some betalactams as well as the structures responsible for the hemotoxic effects of chloramphenicol, the digestive intolerance and hepatotoxic effect of some macrolides, the neurotoxic effects of quinolones, the nephrotoxicity of amphotericin, aminoglycosides, and polymyxin B - colistin . The conclusions to be derived by the prescribing physician are discussed in relation with these aspects.

Chemioterapia, 1987 Aug, 6(4), 269 - 71
New benzofuran-imidazoles as antimycotic agents . I . Synthesis and characterization; Pestellini V et al.; With the aim of obtaining new drugs having antimycotic activity together with antibacterial and fewer side effects, we synthesized ten new benzofuran-2-yl-imidazoles.

Scand J Immunol, 1987 Aug, 26(2), 207 - 11
Circulating cholera antitoxin memory cells in the blood one year after oral cholera vaccination in humans; Lycke N et al.; Oral vaccination with the combined B subunit/whole cell cholera vaccine generates antitoxin memory cells that could be isolated from peripheral blood for at least 1 year after immunization . These memory cells were triggered by antigen in vitro to produce antitoxin in the presence of autologous T cells and monocytes . Antitoxin-producing peripheral blood lymphocytes (PBL) were found in 4 out of 5 previously vaccinated subjects . IgA and IgM isotypes dominated the memory response . The antigen-dose dependency and requirements for a specific ratio of T to B cells for activation of the memory cells in vitro implies T-cell control of antitoxin responses . These antitoxin memory cells in peripheral blood (and corresponding antibacterial memory cells) might represent a pool of circulating cells that on renewed exposure to cholera rapidly produce protective antibody in the gut and thus might have a central role in the long-term protection against reinfection and disease seen in convalescents from cholera.

Br J Urol, 1987 Aug, 60(2), 153 - 6
Oral ciprofloxacin as prophylaxis in transurethral resection of the prostate; Murdoch DA et al.; A new quinolone antibacterial, ciprofloxacin, was evaluated as oral prophylaxis for transurethral resection of the prostate in a randomised controlled trial . A 3-day course of perioperative ciprofloxacin 250 mg twice daily reduced the post-operative infection rate, the post-operative hospital stay and the frequency of infective complications . Ciprofloxacin was well tolerated and no significant haematological or biochemical side effects were detected.

Zentralbl Bakteriol Mikrobiol Hyg {A}, 1987 Jul, 265(3-4), 385 - 92
Uptake of selected antibacterial agents in Mycobacterium avium; David HL et al.; The antibacterial action of 64 drugs against Mycobacterium avium ATCC 15769 was screened in Middlebrook 7H9 liquid medium . The most active drugs were ansamycin, rifampicin, clofazimine, and pristinamycin . The antibacterial action of the selected drugs was confirmed by testing clinical isolates on Middlebrook 7H10 agar medium . The antibacterial actions were not related with the hydrophobicities and molecular weights of the drugs . However, all the active drugs were highly hydrophobic molecules of low polarity . These drugs dissolved into the lipids forming the outer layers of the bacterial envelope and they appeared to interact with the surface amphiphils.

Vopr Med Khim, 1987 Jul-Aug, 33(4), 83 - 6
{Effect of tuberculostatic agents and sodium succinate on the functional state of liver mitochondria in tuberculosis}; Sokirko TA; Effects of isoniazide and of new tuberculostatic drug of long-term action on functions of guinea pig liver mitochondria were studied in experimental tuberculosis . Significant changes in oxidative phosphorylation were found . The combination of sodium succinate with tuberculostatic drugs improved the bioenergetic functions of liver mitochondria under the conditions of antibacterial therapy of experimental tuberculosis.

J Assoc Off Anal Chem, 1987 Jul-Aug, 70(4), 714 - 7
Simultaneous liquid chromatographic determination of residual synthetic antibacterials in cultured fish; Nose N et al.; A liquid chromatographic method is described to determine simultaneously the following 11 synthetic antibacterial agents used in a fishery: nitrofuran derivatives furazolidone, nifurpirinol, difurazone, and furamizole; sulfa drugs sulfamerazine, sulfisozole, sulfamonomethoxine, and sulfadimethoxine; and, oxolinic, nalidixic, and piromidic acids . A Nucleosil C18 column was used with tetrahydrofuran-acetonitrile-phosphoric acid-water (29 + 1 + 0.06 + 69.94) as the mobile phase . Pretreatment of the fish meat sample with acetone extraction and alumina column cleanup gave good separation of the LC peaks without interference from any other components . Recovery of the antibacterial agents was ca 80% . The lower limit of detection of the drugs was 1-2 ng for 10 microL injection.

Am J Dis Child, 1987 Jul, 141(7), 772 - 5
Prescription medications in infancy and early childhood; Fosarelli P et al.; The prescription medication exposures of a cohort of 222 children during their first five years of life were investigated . Excluding the three outliers, the cohort received 1852 medications (average per child, 8.46; mode, six; range, 0 to 37) during 1358 (23%) of the total 6017 visits made in five years . The greatest number of medications were administered or prescribed between 7 and 12 months of age . The majority (62%) of the medications over five years were oral preparations, and 87% were prescribed for two weeks or less . Antibacterials, bronchodilators, and antifungal-anti-yeasts accounted for 80% of the 1852 medication courses . One third of all medications were for ampicillin or amoxicillin . High medication recipients were likely to have chronic conditions, especially recurrent otitis media and/or asthma, and were likely to be high users of our health facility.

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