Antimicrobials

Pharmacoeconomics, 1992 Jun, 1(6), 409 - 37
Pharmacoeconomics of antibacterial treatment; Davey PG et al.; Antibacterial drugs account for between 3 and 25% of all prescriptions, between 6 and 21% of the total market value of drugs in a single country, and up to 50% of the drug budget in hospitals . Bacterial infection is widely perceived as disease caused by harmful outside agents which can be isolated and tested to select the best drug for treatment . In fact, the need for any treatment and the pros and cons of different drugs are just as debatable as in any other therapeutic area . Moreover, the bacteria which make up the normal flora of the body fulfil important roles, so that the ecological implications of treatment for the individual and for society should be considered in assessing the costs and consequences of antibacterial treatment . In this review we outline the most important issues relating to the treatment of bacterial infection in the community and in the hospital, contrasting information from developed and developing countries where appropriate . We review the existing literature on economic evaluation, but in general most of the literature deals with containing the costs of antibacterial drugs in hospitals, and there are many gaps in the literature on cost-effectiveness of treatment . Consequently there are still extreme variations in medical practice which present a challenge for future evaluation . As the outcomes of antibacterial treatment are apparent in a few weeks or months, this is an ideal field for testing pharmacoeconomic methodology . The desire to overcome medical practice variation through consensus statements should be avoided . Instead we recommend wider application of decision analysis to acknowledge that choices exist for the diagnosis and treatment of bacterial infection and to gather information about the implications of these choices . Much of the existing literature would be improved by a more explicit definition of costs . Direct costs to the health services should be distinguished from non medical costs . Moreover, the analysis should consider whether savings from one budget result in costs to another health service budget, or to the patient (transfer costs) . These deficiencies in cost analysis will be relatively easy to correct . Of more concern is the fact that the efficacy of much antibacterial treatment is either totally debatable, or variable, depending on factors such as the type of patient treated or the quality of delivery of treatment.(ABSTRACT TRUNCATED AT 400 WORDS)

Zentralbl Veterinarmed B, 1992 May, 39(3), 165 - 74
Immunoglobulins, lysozyme and lactoferrin in the teat and udder of the dry cow during endotoxin-induced inflammation; Persson K et al.; Immunoglobulins (Ig) and antibacterial proteins like lysozyme and lactoferrin are components of the humoral defence against infections . Changes in Ig, lysozyme and lactoferrin concentrations during endotoxin-induced inflammation in the test cistern and udder quarter of the dry cow were studied . Surgical closure of the passage between teat and udder cisterns enabled studies of reactions in the teat cistern without interference of the mammary gland . After endotoxin infusion, IgG1, IgG2, lysozyme, and to some extent IgM, increased in the teats and udder quarters, and were positively correlated with changes in somatic cell counts . No significant changes were observed in IgA or lactoferrin . The origin and significance of Ig, lysozyme and lactoferrin in the bovine teat and udder are discussed . Ig probably originated both from serum and from local plasma cells, while leukocytes appeared to be the source of lysozyme during inflammation . Secretory epithelium appeared to be the source of lactoferrin . Support for this theory was the almost total absence of lactoferrin in teat cistern samples.

J Antibiot (Tokyo), 1992 May, 45(5), 721 - 34
Studies on condensed-heterocyclic azolium cephalosporins . V . Synthesis and antibacterial activity of 3-(condensed-triazolo-pyridinium, -pyrimidinium, and -pyridazinium)-methyl cephalosporins; Yoshimura Y et al.; As a part of our studies on cephalosporins bearing condensed-heterocyclic azolium methyl groups at the 3 position in the cephalosporin nucleus, we describe here the synthesis and antibacterial activity of 7 beta-{2-(2-aminothiazol-4-yl)2(Z)-methoxyiminoacetamido} cephalosporins (1-16, 7 beta-{2-(2-amino-5-chlorothiazol-4-yl)-2(Z)- methoxyiminoacetamido} cephalosporins (17,18) and 7 beta-{2-(5-amino- 1,2,4-thiadiazol-3-yl)-2(Z)-methoxyiminoacetamido) cephalosporins (19-23) containing a variety of condensed-heterocyclic triazolium methyl groups at the 3 position in the cephalosporin nucleus . These cephalosporins exhibited potent antibacterial activity, and it appears that condensed-heterocyclic triazolium as well as condensed-heterocyclic imidazolium rings are effective moieties for improving antibacterial activity and the spectrum of activity . Among the cephalosporins tested, 7 beta-{2-(2-aminothiazol-4-yl)-2(Z)-methoxyiminoacetamido}-3-(5- methyl{1,2,3}triazolo-{1,5-alpha}pyridinium-1-yl)methyl-3-cephem-4- carboxylate (9) and 7 beta-{2-(2-aminothiazol-4-yl)-2(Z)-methoxyiminoacetamido}-3-(6- methoxy{1,2,4}triazolo{1,5-alpha}pyridinium-1-yl)methyl-3-cephem-4- carboxylate (11) showed good antibacterial activity.

Diagn Microbiol Infect Dis, 1992 May-Jun, 15(4 Suppl), 77S - 79S
Penetration of roxithromycin into gingival tissue; Jehl F et al.; Roxithromycin is a new macrolide with an antibacterial spectrum similar to that of erythromycin . Absorption is rapid and complete, resulting in high serum levels and a long half-life . Tissue distribution is extensive and sustained, as shown by the high concentrations measured in the lung, prostate, ovaries, liver, kidney, and skin . In this study, we measured the penetration of roxithromycin into gingival tissue at steady state in 30 patients treated orally with 150 mg every 12 hr for 5 days . Tissue specimens were sampled at 2, 4, 6, 8, or 12 hr (n = 6 each time) after dose 10, and blood samples were taken simultaneously . Serum and tissue concentrations of roxithromycin were measured by high-performance liquid chromatography . The peak serum level, reached 4 hr after dosing, was 6.60 +/- 1.15 micrograms/ml . The peak tissue level was 4.63 +/- 1.84 micrograms/g and was reached after 8 hr . From 4 to 10 hr after dosing, tissue concentrations were greater than 2 micrograms/g, that is, higher than the MIC90 of roxithromycin against most oral pathogens . These data support the use of roxithromycin in the treatment of oral infections.

Orthop Rev, 1992 May, 21(5), 577 - 9
Tobramycin-impregnated cement in total hip replacements; Pritchett JW et al.; The clinical effect of adding 1.2 g of tobramycin powder to each 40-g pack of powdered polymethylmethacrylate used in hip replacement surgery was investigated . Fifteen patients underwent total hip replacement in which a cemented femoral prosthesis and a cementless acetabular prosthesis were used . Postoperatively, the tobramycin levels in the blood and in the wound drainage fluid were measured . The serum tobramycin concentrations were low, whereas the wound drainage fluid contained highly effective antibacterial concentrations . There was no evidence of reaction or toxicity to the antibiotic-impregnated bone cement.

J Invest Dermatol, 1992 May, 98(5), 725 - 9
Quantitative in vitro assessment of phototoxicity by a fibroblast-neutral red assay; Lasarow RM et al.; We have adapted the neutral red uptake assay for quantitative assessment of injury to fibroblast cultures by potential phototoxins . Tetracycline derivatives, quinolone derivatives, and chlorpromazine were used as model compounds for development of the assay . Human fibroblasts were incubated with potential phototoxins, the cell cultures irradiated with UV, and the capacity for neutral red uptake determined . Demeclocycline and doxycycline, two known photosensitizers, showed a 94% and 95% decrease of neutral red uptake, respectively, indicating photo-induced cytotoxicity . Minocycline, a non-photosensitizing tetracycline derivative, showed no decrease in uptake . Tetracycline, a weak phototoxin, showed minor (10%) decrease at equivalent concentrations (20 micrograms/ml) . Microscopic observation of neutral red uptake and cell damage paralleled the spectrophotometric findings . Chlorpromazine, a non-tetracycline phototoxin, showed 91% decrease . An additional group of phototoxic drugs, quinolone antibacterials, were studied . Nalidixic acid, ofloxacin, ciprofloxacin, and norfloxacin all demonstrated phototoxicity, with nalidixic acid showing the greatest decrease in neutral red uptake . This methodology may provide a useful rapid method to quantify phototoxic potential of new drugs or suspected phototoxins.

Jpn J Antibiot, 1992 May, 45(5), 569 - 75
{Penetration of levofloxacin in bile}; Mizuno A et al.; The penetration into bile of a new pyridonecarboxylic acid derivative, levofloxacin (LVFX), was studied in a closs-over method with ofloxacin (OFLX) as the control drug in 6 post-operative patients . The lengths of time to the maximum concentrations in bile and the total areas under the curves were both almost the same for these 2 compounds, although the maximum bile concentration of LVFX was slightly lower than that of OFLX . A stability test for LVFX in human bile revealed that over 95.4% of the initial amount was recovered up to 24 hours after commencement of incubation at a room temperature, thus the stability in bile was similar to that in water . The penetration of LVFX which possesses twice as strong antibacterial activities as OFLX was similar to that of OFLX, suggesting that LVFX is useful against bile duct infections.

Jpn J Antibiot, 1992 May, 45(5), 557 - 68
{Chemotherapy of biliary tract infections (XXXVII) . Excretion into bile and gallbladder tissue levels of levofloxacin and its clinical effect in biliary tract infections}; Tanimura H et al.; Evaluations were made on biliary excretion and penetration into the gallbladder tissue of levofloxacin (LVFX, DR-3355), a new quinolone antibacterial agent, and its clinical efficacy in biliary tract infections . 1 . Gallbladder tissue concentrations and biliary concentrations of LVFX at 2-6 hours at oral administration of 100 mg were 0.58-1.99 micrograms/g and 0.49-5.63 micrograms/ml, respectively . These tissue and biliary levels are almost equal or somewhat higher than the serum levels (0.55-1.63 micrograms/ml) of the compound . 2 . The concentrations of LVFX and optical isomer DR-3354 in the serum, gallbladder tissue, and bile were determined after a single or a concomitant administration of LVFX 100 mg and/or ofloxacin (OFLX) 100 to 200 mg . The concentration ratio of LVFX to DR-3354 paralleled with the ratio of the 2 compounds administrated . 3 . At a dose of 100 mg, the glucuronide of LVFX in the common duct bile was detected at proportions between 0.9 and 36.0% . 4 . A total of 11 patients with biliary tract infections, including 6 cholecystitis 3 cholangitis, and 1 each of cholecystocholangitis and liver abscess was treated with LVFX at 100-200 mg t.i.d . for 3-14 days . Clinical results were excellent or good in 8 cases and fair in 3 cases, resulting in an efficacy rate of 72.7% . 5 . A side effect and an abnormal change in laboratory findings were observed in both 1 case each and they were both mild . It was concluded that LVFX showed good penetration to the biliary tract as does OFLX, and that it would be a useful oral agent for the treatment of biliary tract infections.

Antimicrob Agents Chemother, 1992 May, 36(5), 942 - 8
Inhibitory potency of quinolone antibacterial agents against cytochrome P450IA2 activity in vivo and in vitro; Fuhr U et al.; Inhibition of cytochrome P450IA2 activity is an important adverse effect of quinolone antibacterial agents . It results in a prolonged half-life for some drugs that are coadministered with quinolones, such as theophylline . The objective of the study described here was to define the parameters for quantifying the inhibitory potencies of quinolones against cytochrome P450IA2 in vivo and in vitro and to investigate the relationship between the results of both approaches . Cytochrome P450IA2 activity in vitro was measured by using the 3-demethylation rate of caffeine (500 microM) in human liver microsomes . The inhibitory potency of a quinolone in vitro was determined by calculating the decrease in the activity of cytochrome P450IA2 caused by addition of the quinolone (500 microM) into the incubation medium . The mean values (percent reduction of activity without quinolone) were as follows: enoxacin, 74.9%; ciprofloxacin, 70.4%; nalidixic acid, 66.6%; pipemidic acid, 59.3%; norfloxacin, 55.7%; lomefloxacin, 23.4%; pefloxacin, 22.0%; amifloxacin, 21.4%; difloxacin, 21.3%; ofloxacin, 11.8%; temafloxacin, 10.0%; fleroxacin, no effect . The inhibitory potency of a quinolone in vivo was defined by a dose- and bioavailability-normalized parameter calculated from changes of the elimination half-life of theophylline and/or caffeine reported in previously published studies . Taking the pharmacokinetics of the quinolones into account, it was possible to differentiate between substances with and without clinically relevant inhibitory effects by using results of in vitro investigations . The in vitro test described here may help to qualitatively predict the relevant drug interactions between quinolones and methylxanthines that occur during therapy.

Klin Med (Mosk), 1992 May-Jun, 70(5-6), 17 - 9
{Detoxication methods in pancreatogenic enzymatic peritonitis}; Medvedenko AF et al.; A therapeutic response was analyzed in 536 patients with acute destructive pancreatitis complicated by pancreatogenic enzymatic peritonitis . All the patients had the syndrome of endogenic intoxication and underwent intensive resuscitation with protease inhibitors, cytostatic agents, antibacterial, desensitization and detoxication treatment . If indicated, the patients with pronounced endogenic intoxication were subjected to forced diuresis, abdominal laparoscopic drainage and intraperitoneal dialysis, drainage of the thoracic lymphatic duct, hemosorption . Routine surgical intervention was performed . Up to 11% fell the general lethality due to a differentiated therapeutic approach.

Clin Ter, 1992 May, 140(5), 481 - 5
{Short-term perioperative antibacterial prophylaxis using imipenem-cilastatin versus acylureide penicillins in pacemaker implantation . A 30-month follow-up}; Veneziani N et al.; The authors have evaluated the efficacy of short term treatment with an imipenem-cilastatin combination in a selected group of 72 patients undergoing implant or substitution of a pacemaker and with associated pathology potentially increasing the risk of infection . After 30 months' follow-up, the authors underline the efficacy and advantages of this treatment.

Antibiot Khimioter, 1992 May, 37(5), 35 - 8
{Prevention of early inflammatory complications after transthoracic interventions and estimation of the degree of immunologic deficiency}; Radomskii VT et al.; An analysis of the results of the examination and treatment of 379 patients undergoing transthoracic interventions showed that the use of the target-aimed selective immunomodulation, short-term antibacterial prophylaxis, inhibitors of arachidonic acid metabolites, active elimination of the circulating immune complexes and medium-weight molecular peptides and adequate local analgesia after the interventions providing normalization of the laryngeal reflex and early activation of the patients permitted the incidence of the pulmonary complications to be decreased by 2.5 times, pleural complications by 1.7 times, suppuration of the postoperative wound by 1.8 times and the total expenses by 25.6 per cent.

Pharmazie, 1992 May, 47(5), 340 - 3
Synthesis and biological activity of some heterocyclic systems containing anthraquinone; Berghot MA et al.; 2-Aminoanthraquinone (1) was reacted with ethyl chloroformate to afford 2 . The reaction between carbamate 2 and hydrazine hydrate gave semicarbazide 3, which on treatment with benzoic acid, phenyl isothiocyanate and carbon disulfide/potassium hydroxide furnished oxadiazoles 4, 6 and triazole 5, respectively . Also, treatment of 1 with chloroacetyl chloride gave chloroacetyl derivative 8 . The reaction of glycolic acid, thioglycolic acid, diethyl malonate and malononitrile with 8 has been investigated . Compound 8 was treated with potassium thiocyanate to give 12, which was cyclized to 13a, while the reaction between 8 and potassium cyanate gave 13b directly . The structures of hitherto unknown compounds were confirmed by analytical and spectral methods . Some of the synthesized compounds were screened to test their antibacterial and antifungal properties.

Eur J Epidemiol, 1992 May, 8(3), 407 - 21
Drug resistance in human pathogenic fungi; Iwata K; Since the therapy of the mycoses, particularly the systemic mycoses, is relatively long-term in nature, emergence of resistance to antifungal drugs during the treatment of period would be of considerable clinical importance . However, most reports of resistance to antifungal agents among human pathogenic fungi indicate that naturally-occurring resistance is very rare, and that the induction of resistant mutants or variants is much more difficult to achieve in vitro and in vivo than with bacteria . As a matter of fact, amphotericin B and some other classic antifungals have not as yet posed a broadly significant problem relative to drug resistance despite their widespread and frequent use . Fungal resistance has thus received little attention, in contrast to the critical importance of bacterial resistance frequently caused by a variety of antibacterial chemotherapeutic agents, until a single exception to this generalization arose with the advent of flucytosine . This new development has aroused great interest in the problem of fungal resistance among the scientists involved with medical mycology . It is generally believed that fungi, like bacteria, are intrinsically capable of developing resistance to antifungal agents . As illustrated by flucytosine, inherently resistant mutants to antifungals occur within sensitive strains of human pathogenic fungi with significant frequency . Given the relatively high degree of such primary resistance, these mutants should develop secondary resistance during therapy, thus resulting in considerable limitations in the clinical usefulness of the antifungals . Virtually, all unsuccessful cases of mycoses treated with some of the recently exploited antifungal drugs, albeit scarce to date, would obviously be attributable to the occurrence of secondary resistance . The exploitation of new antifungal drugs thus requires investigations of their resistance as one of the most important research projects to be undertaken before receiving approval for use on humans . This paper reviews from various aspects the literature on resistance to various classic and novel antifungal agents among human pathogenic fungi . The resistance of some nonpathogenic fungi to these agents will also be described from genetic and biochemical points of view.

J Biomol NMR, 1992 May, 2(3), 235 - 56
Two-dimensional 1H NMR study of recombinant insect defensin A in water: resonance assignments, secondary structure and global folding; Bonmatin JM et al.; A 500 MHz 2D 1H NMR study of recombinant insect defensin A is reported . This defense protein of 40 residues contains 3 disulfide bridges, is positively charged and exhibits antibacterial properties . 2D NMR maps of recombinant defensin A were fully assigned and secondary structure elements were localized . The set of NOE connectivities, 3JNH-alpha H coupling constants as well as 1H/2H exchange rates and delta delta/delta T temperature coefficients of NH protons strongly support the existence of an alpha-helix (residues 14-24) and of an antiparallel beta-sheet (residues 27-40) . Models of the backbone folding were generated by using the DISMAN program and energy refined by using the AMBER program . This was done on the basis of: (i) 133 selected NOEs, (ii) 21 dihedral restraints from 3JNH-alpha H coupling constants, (iii) 12 hydrogen bonds mostly deduced from 1H/2H exchange rates or temperature coefficients, in addition to 9 initial disulfide bridge covalent constraints . The two secondary structure elements and the two bends connecting them involve approximately 70% of the total number of residues, which impose some stability in the C-terminal part of the molecule . The remaining N-terminal fragment forms a less well defined loop . This spatial organization, in which a beta-sheet is linked to an alpha-helix by two disulfide bridges and to a large loop by a third disulfide bridge, is rather similar to that found in scorpion charybdotoxin and seems to be partly present in several invertebrate toxins.

Curr Genet, 1992 May, 21(6), 443 - 6
Ofloxacin induces cytoplasmic respiration-deficient mutants in yeast Saccharomyces cerevisiae; Obernauerova M et al.; Ofloxacin, a new quinolone with potent antibacterial activity, was also found to be effective against yeast . At relatively high concentrations, and at mild alkaline pH, ofloxacin inhibited the growth of yeast cells in medium containing glucose, and prevented growth on glycerol, as carbon and energy source . The cells growing in the presence of ofloxacin exhibited abberrantly budded forms, lost their viability and many of them converted to cytoplasmic respiration-deficient mutants . Induction of mutants was also observed under non-growing conditions . The petite clones analysed exhibited suppressiveness and contained different fragments of the wild-type mitochondrial genome.

Vestn Oftalmol, 1992 May-Jun, 108(3), 29 - 30
{Pathogenetic therapy of spontaneous corneal perforation after extracapsular cataract extraction}; Manukian ME; The author presents a case with spontaneous perforation of the cornea after extracapsular cataract extraction in a female patient with rheumatoid arthritis . Systemic disorganization of the connective tissue and elevated collagenase activity essentially contribute to the pathogenesis of corneal perforation . Therefore, besides antibacterial drugs, collagenase inhibitors, 3% aqueous solution of cysteine, antimeasles gamma-globulin, and a regeneration stimulant, 5% ascorbic acid aqueous solution, were used in the treatment . The pathogenetic therapy was conducive to early healing of the corneal defect and helped save the eye and preserve its good function (0.8 s + 10.0 diopters).

J Med Chem, 1992 Apr 17, 35(8), 1385 - 92
Pyrimido{1,6-a}benzimidazoles: a new class of DNA gyrase inhibitors; Hubschwerlen C et al.; Substituted 4-quinolone- (1, A = CH) and 1,8-naphthyrid-4-one- (1, A = N) 3-carboxylic acids are currently the only classes of clinically useful antibacterial agents exerting their activity by inhibiting the subunit A of DNA gyrase . Pyrimido{1,6-alpha}benzimidazoles 11 have been found to be a new class of inhibitors of this enzyme . The design, synthesis, and biological activity of these compounds are reported.

Rev Prat, 1992 Apr 15, 42(8), 943 - 5
{Principles of the treatment of ocular infections}; Bron A; Ocular infections are still quite common and their clinical presentation is variable; some of them may lead to blindness . In this paper only severe infections like keratitis and endophthalmitis are considered . The rationale for treatment and prophylaxis is based upon bacteriological findings, understanding of ocular barriers and pharmacokinetics of antibacterial agents.

Med Klin (Munich), 1992 Apr 15, 87(4), 179 - 84
{Polymorphism in Helicobacter pylori--a key function in recurrence of infection?}; Bode G et al.; Despite the fact that Helicobacter (H.) pylori is ubiquitous throughout the world, little is known at present about the source of infection and mode of transmission . Person-to-person transmission may be of importance . The fact that Helicobacter pylori can revert to a coccoid form stimulated speculation about its role in transmission and as a possible cause of reinfection in duodenal ulcer disease . Various antibacterial agents (bismuth subcitrate 32 mg/l bismuth subsalicylate 64 mg/l, amoxicillin 0.05 mg/l, ampicillin 2 mg/l, erythromycin 4 mg/l, glycochenodeoxycholic acid 423 mg/l, ursodeoxycholic acid 540 mg/l) inhibit the growth of H . pylori and stimulate the formation of coccoid structures . Ultrastructural and biochemical results show that the coccoid form meets the necessary criteria for survival . Thus, to be successful, treatment must aim not only at eliminating the vegetative form, but also at preventing the development of the coccoid form.

Am J Med, 1992 Apr 6, 92(4A), 91S - 97S
Diagnosis and interventions in lower respiratory tract infections; Wijnands GJ; In the elderly and in immunocompromised patients, respiratory tract infections are still a major cause of morbidity and mortality . The choice of a specific antibiotic treatment in pneumonia depends on the identification of the causative pathogen or on a judgment concerning the probable causative micro-organism . This judgment should be based on all the information obtained from clinical signs and symptoms, laboratory investigations of sputum and blood, and the pattern of infiltrations on chest X-ray . Different causative pathogens can be expected in bacterial and "atypical" community-acquired pneumonia than in hospital-acquired pneumonia . For the same reason, immunocompetent and immunocompromised patients have to be distinguished from each other . In chronic obstructive pulmonary disease, bronchial defenses will be impaired . Exacerbations can result from different causes, including infections of the bronchial mucosa . Most of these infections are of viral origin . Exacerbated pulmonary disease will result from bacterial bronchitis only in some patients . It is often difficult to assess the diagnosis "bacterial bronchitis." Evaluation of the effect of antibacterial treatment in exacerbated pulmonary disease is also difficult . Therapeutic interventions for these clinical conditions have to be directed primarily toward restoring or improving pulmonary host-defense factors . Fluoroquinolones, including lomefloxacin, have been shown to be effective in the treatment of lower respiratory tract infections caused by susceptible bacteria . Lomefloxacin presents a number of advantages: the drug has good bioavailability after oral and parenteral administration and penetrates well into bronchial secretions and lung tissue . In addition, lomefloxacin has no influence on the metabolic clearance of the methylxanthines theophylline and caffeine, which has been demonstrated for enoxacin, ciprofloxacin, and pefloxacin.

Am J Med, 1992 Apr 6, 92(4A), 8S - 11S
Penetration of lomefloxacin into bronchial secretions following single and multiple oral administration; Bergogne-Berezin E et al.; The bronchial penetration of lomefloxacin, a new difluorinated quinolone, was evaluated in 36 patients who underwent bronchoscopies for diagnostic purposes . Patients were randomized into two groups, with 18 patients (Group I) receiving a single oral dose of 400 mg lomefloxacin and 18 patients (Group II) receiving 400 mg twice daily . Samples of serum and bronchial secretions were collected simultaneously in both groups at 1, 2, or 4 hours after lomefloxacin administration . The results of this study showed that bronchial penetration of lomefloxacin was rapid and yielded high concentrations; the mean bronchial levels of the drug reached 2.78 +/- 3.64 micrograms/mL in Group I 1 hour after the dose, and 2.84 +/- 1.73 micrograms/mL in Group II at the fourth hour . The ratio between bronchial and simultaneous serum concentrations was 89% at the first and second hours after the dose for Group I, and it was 77% 4 hours after oral administration in Group II . In comparing these results to previous reports of lomefloxacin penetration into bronchial mucosa or of concentrations of other new fluoroquinolones into bronchial secretions, it is to be noted that the local concentrations of the newer quinolones are of very similar values, ranging from 2.7 micrograms/mL (ofloxacin) to 4.46 micrograms/mL (pefloxacin) . This study confirms that lomefloxacin achieves high tissue concentrations in the respiratory tree; this characteristic, together with lomefloxacin's antibacterial spectrum, indicates promise in the treatment of many respiratory infections.

J Antibiot (Tokyo), 1992 Apr, 45(4), 535 - 41
Synthesis and antibacterial activities of new 3-phenoxymethylcephalosporins; Koyama K et al.; The synthesis and biological properties of new 3-phenoxymethylcephalosporins (1) are described . These compounds exhibited good antibacterial activity against Gram-positive and Gram-negative bacteria.

J Antibiot (Tokyo), 1992 Apr, 45(4), 500 - 4
New penem compounds with 5'-substituted pyrrolidinylthio group as a C-2 side chain; comparison of their biological properties with those of carbapenem compounds; Sunagawa M et al.; A series of new penem compounds with a C-2 side chain consisting of a pyrrolidin-3'-ylthio group substituted with various aminocarbonyl groups at the C-5' position have been prepared . Antibacterial activity, stability to renal dehydropeptidase-I and affinity to penicillin-binding proteins of these compounds were investigated and compared with the corresponding carbapenem compounds.

J Antibiot (Tokyo), 1992 Apr, 45(4), 454 - 7
10'-Desmethoxystreptonigrin, a novel analog of streptonigrin; Liu WC et al.; 10'-Desmethoxystreptonigrin, a novel analog of streptonigrin produced by Streptomyces albus, was discovered in a screen for inhibitors of farnesylation of RAS p21 protein . The compound was isolated from the fermentation broth and its structure determined . It is markedly cytotoxic to several human tumor cell lines and also exhibits potent broad-spectrum antibacterial activity.

Mol Gen Genet, 1992 Apr, 232(3), 335 - 43
The lysozyme locus in Drosophila melanogaster: different genes are expressed in midgut and salivary glands; Kylsten P et al.; As part of a study of the genes involved in antibacterial defense in Drosophila melanogaster, we have isolated genomic clones harboring a family of chicken-type lysozyme genes, using a lepidopteran lysozyme cDNA as probe . The locus was mapped to the cytological location 61F1-4 on the third chromosome and two of the genes at this locus, LysD and LysP, were analyzed in detail . In contrast to the bacteria-induced lysozymes in the hemolymph of many insects, the transcription levels of both Drosophila genes decrease after bacterial injections into the hemocoel . Apparently, these gene products, like the specifically adapted lysozymes in mammalian foregut fermenters, have been recruited for the digestion of bacteria present in fermenting food . The LysD gene is expressed in an anterior section of the midgut during all feeding stages of development in both larvae and adults . The LysP gene is only active in the adult where it is expressed in the salivary glands . The transcription units for both genes are very compact and they lack introns . Lysozyme D is unusual in that it is predicted to have an acidic isoelectric point whereas lysozyme P appears to be a typical basic lysozyme.

J Leukoc Biol, 1992 Apr, 51(4), 316 - 23
A neutrophil-derived proteolytic inactive elastase homologue (hHBP) mediates reversible contraction of fibroblasts and endothelial cell monolayers and stimulates monocyte survival and thrombospondin secretion; Ostergaard E et al.; Human heparin-binding protein (hHBP) is a recently discovered proteolytically inactive neutrophil elastase homologue with sequence identity to azurocidin and CAP37 . The protein has antibacterial properties and chemotactic activity toward monocytes . In the present work, we show that monocytes, cultured under serum-free conditions, developed morphological changes and formed multicellular aggregates 4 h after the addition of hHBP at a concentration of 10 micrograms/ml . However, after prolonged incubation (11 days) with unchanged medium, the cells spread again . The hHBP-treated cells had a two- to threefold increase in survival compared to control cells, measured using trypan blue as an indicator of living cells . Differentiation of the alive cells to macrophages was detected by changes in morphology, a threefold increase in protein content, and a three- to fourfold increase in acid phosphatase activity . When monocytes in parallel experiments were labelled with {35S}methionine de novo synthesis and secretion of thrombospondin in a dose-dependent manner was observed after 16 h, with half-maximal secretion at 2 micrograms hHBP/ml and a maximal 12-fold increase in secretion with respect to controls at 16 micrograms/ml . Supplementary labeling with {35S}sulfate revealed that the same monocytes down-regulated the secretion of a large proteoglycan (300-400 kd), apparently also with a half-maximal decrease rate at 2 micrograms/ml hHBP . Exposure of confluent fibroblast and endothelial cell monolayers to hHBP (10 micrograms/ml) in the absence of fetal calf serum resulted in cell contraction leaving gaps between cells, the phenomenon being recognizable within 4 h after addition of hHBP . Addition of fetal calf serum to a concentration of 10% completely restored the monolayers . A unique role of hHBP in host defense involving recruitment of monocytes and a key function of hHBP in neutrophil extravasation in response to inflammatory chemotactic signals such as leukotriene B4, complement peptide C5a, and N-formyl-methionyl-leucyl-phenylalanine are suggested.

J Antibiot (Tokyo), 1992 Apr, 45(4), 476 - 84
New polyenic antibiotics active against gram-positive and gram-negative bacteria . VIII . Construction of synthetic medium for production of mono-chloro-congeners of enacyloxins; Watanabe T et al.; New antibiotics enacyloxins (ENXs) are a family of non-lactonic polyene antibiotics produced by Frateuria sp . W-315 . For the production of antibiotics, we had to employ two-step fermentations, the first is the production of spent medium of Neurospora crassa and the second is the production of antibiotics by Frateuria . To simplify the production of antibiotics, systematic analyses have been done on the spent medium, and factors which affect the production of antibiotics characterized . From the above results, we constructed a new medium for antibiotic production . Moreover, we could get a new antibiotic named enacyloxin IIIa (1), C33H48O11NCl (m/z 669) . 1 was deduced to be one of the congeners of enacyloxins because it was similar to ENX IIa or ENX IVa both in biological and physico-chemical properties . Chlorine of 1 could be replaced by bromine, biosynthetically, and the resultant bromine-containing antibiotic also showed an antibacterial activity comparable to 1.

Pharmazie, 1992 Apr, 47(4), 258 - 61
{Azoles . 34 . Nitroimidazole derivatives and their antibacterial and fungicidal action}; Zaprutko L et al.; Nitroimidazole derivatives 4a-4c, 5a-5c, 8a-8c and 9a-9c were synthesized by treating 4,5-dinitro- and 2-methyl-4,5-dinitroimidazole (1,2) or their silver salts {1.Ag,, 2.Ag) with chlorosubtituted phenacyl bromides 3a-3c, diethyl sulphate or ethyl iodide, allyl iodide and ethyl chloro-, azo- or bromoacetate . 2,4(5)-dinitroimidazole (10) has been converted to the 2,4-dinitroimidazole derivative 10a by the action of ethyl bromoacetate in the presence of sodium ethylate . A modified method for the synthesis of 6a and 6b has been described . 7a and 7b have been obtained by a known method . Some of the newly synthesized nitroimidazole derivatives show antibacterial and fungicidal activity.

Antimicrob Agents Chemother, 1992 Apr, 36(4), 840 - 50
Iron transport-mediated antibacterial activity of and development of resistance to hydroxamate and catechol siderophore-carbacephalosporin conjugates; Minnick AA et al.; Peptides containing residues of N5-acetyl-N5-hydroxy-L-ornithine were evaluated as potential artificial siderophores of beta-lactam-hypersusceptible Escherichia coli X580 . Only those peptides which were capable of forming a hexadentate complex around ferric iron, which is analogous to the natural siderophore ferrichrome, were able to reverse the growth inhibition effects of the ferric iron chelator ethylenediamine di(o-hydroxyphenylacetic acid) . A synthetic bis(catechol) spermidine derivative, similar to the natural siderophores enterobactin and agrobactin, also exhibited siderophore activity with this strain . Conjugation of the N5-acetyl-N5-hydroxy-L-ornithine tripeptide and the bis(catechol) siderophore to the potent carbacephalosporin loracarbef and closely related analogs provided compounds which exhibited antibacterial activity against E . coli X580 . As was observed with the naturally occurring albomycins, the initial bactericidal effect was followed by the appearance of survivors that were resistant to the test compound . An enhanced killing effect was observed when the parent was incubated simultaneously with hydroxamate and catechol siderophore-antibiotic conjugates . Natural and synthetic siderophore growth promotion experiments with survivors resistant to the conjugates strongly suggested that disabled ferrichrome and enterobactin-catechol assimilation mechanisms may be responsible for the observed resistance . One isolated survivor was postulated to be a tonB mutant . The antibacterial activities of the described siderophore-carbacephalosporin conjugates appear to be related to an iron transport assimilation mechanism and would not have been detected during routine MIC testing procedures.

Photodermatol Photoimmunol Photomed, 1992 Apr, 9(2), 86 - 8
Enoxacin-induced photosensitivity: study of two cases; Izu R et al.; Enoxacin is a second-generation quinolone derivative recently introduced in Spain . Its activity comes through the inhibition of bacterial DNA-gyrase and it has a good antibacterial capacity against a broad spectrum of gram-positive and gram-negative bacteria . It is presumed to be less toxic than the rest of the quinolones and its use is increasing, specially to treat infections of the urogenital tract . Cases of photosensitivity to enoxacin have been very rarely reported . We describe 2 patients with photosensitivity reactions due to this drug.

Lik Sprava, 1992 Apr, (4), 65 - 8
{Secondary pneumonia in subjects with acute leukemia}; Mazurov VI et al.; Of 105 patients with acute leukoses secondary pneumonias were found in 47.6% . A dependence was found of the frequency of pneumonia on the severity of initial hyperleukocytosis and duration of post-cytostatic agranulocytosis . The efficiency of routine criteria of diagnosis was 66% and increased significantly in microbiological and cytological investigation of the bronchoalveolar lavage fluid . Treatment: combined antibacterial therapy, antifungal, desintoxicating agents; in severe cases--endobronchial administration of monogroup leucocytic mass.

Bratisl Lek Listy, 1992 Apr, 93(4), 183 - 8
{Prophylactic administration of selected antibiotics in hospitals in the Slovak Republic}; Antal M et al.; Over a period of ten years prophylactic administration of selected antibiotics was evaluated three times (in 1973, 1983, and in 1988) in the same ten hospitals of the Slovak Republic . The study was focused on the use of gentamicin (GEN), cotrimoxasol (COT) and cephalosporins (CEP) . Prophylactic administration of antibiotics was found to be increasing . GEN is being given less frequently, while CEP are administered more often, which is considered to be a positive trend . The period of prophylactic administration of antibiotics is still inadequately long with an average of 10.7 days . Evaluation of antibiotic administration showed that antibacterial substances have the highest rate of prophylactic administration in patients with oncologic diseases, followed by patients with diseases of the urinogenital system . A positive development was recorded in the perinatal period with a decreasing trend in the prophylactic administration of antibiotics.

EMBO J, 1992 Apr, 11(4), 1469 - 77
Insect immunity: developmental and inducible activity of the Drosophila diptericin promoter; Reichhart JM et al.; Diptericins are 9 kDa inducible antibacterial peptides initially isolated from immune haemolymph of Phormia (Diptera) . Following the isolation of a Drosophila cDNA encoding a diptericin homologue, we have now cloned a genomic fragment containing the Drosophila diptericin gene . To dissect the regulation of this gene, we have transformed flies with a fusion gene in which the reporter beta-galactosidase gene is under the control of 2.2 kb upstream sequences of the diptericin gene . We show that such a fusion gene is inducible by injection of live bacteria or complete Freund's adjuvant and respects the tissue specific expression pattern of the resident diptericin gene . Our analysis reveals at least four distinct phases in the regulation of this gene: young larvae, late third instar larvae, pupae and adults . This complexity may be related to the presence in the upstream sequences of multiple copies of response elements previously characterized in genes encoding acute phase response proteins in mammals (e.g . NK-kappa B, NF-kappa B related, NF-IL6 response elements).

J Periodontol, 1992 Apr, 63(4), 280 - 2
Antibacterial activity of some triclosan-containing toothpastes and their ingredients; Wade WG et al.; The antibacterial activity of 4 triclosan-containing toothpastes was compared to a conventional fluoride dentifrice and triclosan and sodium lauryl sulphate (SLS), both singly and in combination . A panel of 17 bacteria was tested by an agar dilution method . At concentrations typical of those found in toothpastes, triclosan and SLS displayed approximately equal antibacterial activity . A paste containing triclosan and zinc citrate appeared more active than the other triclosan pastes which, in general, showed marginal superiority over the conventional paste . SLS, although included in dentifrice formulations for its detergent properties, may significantly contribute to the antibacterial profile of a product . The need for appropriate controls when evaluating experimental toothpastes is emphasized.

Rev Med Chil, 1992 Apr, 120(4), 439 - 44
{Mechanisms of the antibiotic activity of bacteriocins}; Garcia-Quintana H; Some bacteria possesses the genetic capacity to synthesize compounds referred to as bacteriocins; such compounds are antagonic for other closely related bacteria by inhibiting bacterial growth . These toxic substances are either simple polypeptides or very complex macromolecules . However the feature of being a "killer" strain is coded by chromosomal or plasmid genes . The mechanism of lethal action is carried out either directly or indirectly against certain functions of the target cell; death of the sensitive strain is produced as a consequence of transport collapse at membrane level resulting in a drastic drop of indispensable metabolites or ions; in other cases the antibacterial effect produces blocking of macromolecule synthesis; or loss of metabolite stabilization within the cell altering the basic metabolism . Repercussions of bacteriocinogeny may be: use as epidemiological tool through bacteriocin-typing techniques; biological control by means of specific bacteriocins; regulation of bacterial growth rate in a population as a competence mechanism for a given ecological habitat; genetic transfer between competent cells; study of superficial receptor sites and its role in natural immunity; use as therapeutic agents through a number of problems like cross-toxicity and specificity of action still remain unsolved.

Antimicrob Agents Chemother, 1992 Apr, 36(4), 833 - 9
Efficacy and safety of temafloxacin versus those of amoxicillin in hospitalized adults with community-acquired pneumonia; Carbon C et al.; Temafloxacin, a new fluoroquinolone, was compared with amoxicillin in the treatment of adult hospitalized patients with community-acquired pneumonia . In this double-blind, multicenter study, patients were randomly assigned to treatment with temafloxacin at 600 mg twice daily (n = 125) or amoxicillin at 500 mg three times daily (n = 121); the average duration of treatment was 10 days . Clinical recovery rates were similar for patients treated with temafloxacin and amoxicillin (89 and 85%), as were bacterial eradication rates (99 and 97%) . This was also true for subgroups of patients with pneumococcal pneumonia (n = 100), nonpneumococcal pneumonia (n = 122), or atypical pneumonia (n = 12) . Outcomes for temafloxacin- and amoxicillin-treated patients were also similar in terms of defervescence, improvement in leukocytosis, and radiographic evidence of infection . The frequency and severity of adverse events were similar in both groups, consisting primarily of digestive disorders and skin manifestations . We conclude that temafloxacin may be recommended as an alternative antibacterial drug for patients with suspected pneumococcal pneumonia who fail to respond to benzylpenicillin or amoxicillin when the incidence of multiresistant pneumococcal strains is low . In countries where the incidence of these strains is high, temafloxacin may also be recommended.

J Antibiot (Tokyo), 1992 Apr, 45(4), 527 - 34
Synthesis and antibacterial activity of O-methylazithromycin derivatives; Kobrehel G et al.; A series of O-methylazithromycin derivatives have been synthesized and their antibacterial activities were compared with those of azithromycin (1) . O-Methylation of 1 proceeded stepwise by the two main pathways beginning at the C-6 and C-11 hydroxyl groups, individually . Among O-methyl derivatives, 6-O-methylazithromycin A (11) was slightly less active than 1 . The methylation of the secondary hydroxyl group at the C-11 position resulted surprisingly in an increase of their in vitro activity . The antibacterial activities of novel azalides decreased with increasing the number of the methyl groups introduced.

J Med Chem, 1992 Mar 6, 35(5), 953 - 8
Synthesis and antibacterial activity of some novel 6-methyl- and 6-propenyl-substituted carbapenems; Mastalerz H et al.; The synthesis and antibacterial activity of a number of 6-methyl- and 6-propenyl-substituted carbapenems is described . The 6-(hydroxymethyl)- and 6-(aminomethyl)carbapenems possessed more potent antibacterial activity in vitro than their respective 6-(1'(R)-hydroxyethyl) or 6-(1'(R)-aminoethyl) counterparts . However, because of reduced stability, the 6-(aminomethyl)carbapenem was found to be inactive in vivo . All 6-hydroxypropenyl or 6-aminopropenyl derivatives that were prepared were less active than their respective 6-heteroethyl-substituted analogues.

J Med Chem, 1992 Mar 6, 35(5), 939 - 44
Secondary metabolites by chemical screening . 17 . Nigericinol derivatives: synthesis, biological activities, and modeling studies; Grabley S et al.; The synthesis and the biological activity of C-1-reduced nigericin derivatives (nigericinols) are described and discussed . The dichloronigericinol 7 impressively demonstrated that the C-1 carboxylic acid moiety was not required for a distinct activity against bacteria and viruses . Based on the correlation between K+/H+ antiport activities and antibacterial activities it was deduced that the mode of action of the described nigericinols are related to their ionophoric properties . Molecular modeling studies showed that the efficiency of the nigericinols as ionophores correlates, qualitatively, with the probability of forming a cyclic structure, with the exception of 7.

J Pharm Sci, 1992 Mar, 81(3), 237 - 40
Effect of basic cholane derivatives on intestinal cholic acid metabolism: in vitro and in vivo activity; Roda A et al.; A representative series of hydroxy-5 beta-cholanyl-24-amines were tested both in vitro and in vivo with respect to their activity against the intestinal bacteria responsible for bile acid metabolism . For the in vitro studies, radiolabeled {14C}cholic acid was incubated with human stools both in aerobic and anaerobic conditions in the presence of the title compounds at a dose of 10 micrograms/mL, and the biotransformation of cholic acid into radiolabeled deoxycholic acid and other metabolites was followed by TLC-radiochromatography . Of the compounds studied, 3 alpha, 12 alpha-dihydroxy-5 beta-cholan-24-N-methylamine showed the highest activity . This compound was used for the in vivo studies and was shown to inhibit the formation of endogenous secondary bile acids when chronically administered to rats at a dose of 60 micrograms/day for 15 days . The treated rats showed an increased ratio of taurocholic acid (primary bile acid) to taurodeoxycholic acid (secondary bile acid) in bile, a fact further suggesting a potent antibacterial activity of the compound toward bacteria responsible for bile acid metabolism.

Kansenshogaku Zasshi, 1992 Mar, 66(3), 349 - 53
{Contamination of endoscopes and endoscope washers by atypical mycobacteria}; Negayama K et al.; Contamination of endoscopes and endoscope washers by atypical mycobacteria was studied . Large amounts of atypical mycobacteria were detected with high frequency inside endoscopes and endoscope washers . The species of atypical mycobacteria was Mycobacterium chelonae subsp . abscessus . Antibacterial-effects of glutaraldehyde against isolated atypical mycobacteria were checked . Sufficient antibacterial-effect was not obtained by 2% glutaraldehyde solution for endoscope sterilization . However, after frequent manual washing and brushing of endoscopes, by using 3% glutaraldehyde solution and 70% alcohol, all endoscopic instruments were completely decontaminated . We must pay attention to contamination of endoscopes and endoscope washer at least once a month.

Arzneimittelforschung, 1992 Mar, 43(3A), 406 - 8
Interaction of the new quinolone antibacterial agent levofloxacin with fenbufen in mice; Furuhama K et al.; The interaction of (-)-(S)-9-fluoro-2,3-dihydro-3-methyl-10-(4-methyl-1- piperazinyl)-7-oxo-7H-pyrido{1,2,3-de} {1,4}benzoxazine-6-carboxylic acid hemihydrate (levofloxacin, DR-3355, CAS 100986-85-4) with fenbufen, a nonsteroidal anti-inflammatory agent, in mice was assessed by convulsive seizure and subsequent death in comparison with that of other new quinolones such as DR-3354 (the R-(+)-isomer of ofloxacin), ofloxacin, norfloxacin, enoxacin and ciprofloxacin . Although treatment with each quinolone or fenbufen alone at a dosage level tested in mice showed no changes, coadministration of a large dose of all quinolones and fenbufen caused convulsant death . When compared with the severity of this interaction, it was in the order of enoxacin greater than norfloxacin greater than ciprofloxacin greater than DR-3354 greater than ofloxacin greater than or equal to DR-3355 under these experimental conditions.

Arzneimittelforschung, 1992 Mar, 43(3A), 404 - 5
Phototoxic potential of the new quinolone antibacterial agent levofloxacin in mice; Wagai N et al.; The phototoxic potential of (-)-(S)-9-fluoro-2,3-dihydro-3-methyl-10-(4- methyl-1-piperazyl)-7-oxo-7H-pyrido{1,2,3-de}{1,4}benzoxazine-6- carboxylic acid hemihydrate (levofloxacin, DR-3355, CAS 100986-85-4) was evaluated by the mice ear swelling reaction . Results were compared with those for enoxacin (ENX) . Mice were orally administered DR-3355 or ENX and immediately exposed to ultraviolet-A for 4 h . Phototoxicity was determined by measuring ear thickness developing 24 h after irradiation . DR-3355 provided no changes in the ear at 200 mg/kg, but caused ear swelling at 800 mg/kg . ENX caused severe phototoxicity in a dose dependent manner from 50 mg/kg . These data suggest that DR-3355 has minor phototoxic potential, but is approximately 4-fold less toxic than ENX in these experimental conditions.

Arzneimittelforschung, 1992 Mar, 43(3A), 398 - 403
Ophthalmotoxicity and ototoxicity of the new quinolone antibacterial agent levofloxacin in Long Evans rats; Nomura M et al.; An ophthalomo- and ototoxicity study of a new quinolone antibacterial agent, (-)-(S)-9-fluoro-2,3-dihydro-3-methyl-10-(4-methyl-1- piperazinyl)-7-oxo-7H-pyrido{1,2,3-de} {1,4}benzoxazine-6-carboxylic acid hemihydrate (levofloxacin, DR-3355, CAS 100986-85-4) was investigated in Long Evans rats . The rats were orally administered 100 mg/kg of DR-3355, ciprofloxacin (CPFX), norfloxacin (NFLX) or nalidixic acid (NA) for 2 weeks, and the effects on visual and auditory functions were examined . Examination of electroretinograms (ERGs) revealed a decrease in the amplitudes of the a- and b-waves, a prolongation of the latency and diminution or disappearance of oscillatory potential waves in NA treated rats . Similar but milder changes were also noted in the NFLX treated rats . ERGs from DR-3355 or CPFX treated rats were normal . Histopathological examination revealed no changes suggestive of ophthalmotoxicity or ototoxicity in the rats treated with DR-3355, CPFX or NFLX . On the other hand, NA treated rats showed partial loss of the outer hair cells of the organ of Corti in the cochlea, suggesting that NA had slight ototoxicity . DR-3355 did not show any deleterious visual or auditory effects at the dose used in this study.

Arzneimittelforschung, 1992 Mar, 43(3A), 395 - 7
Lack of nephrotoxic effects of the new quinolone antibacterial agent levofloxacin in rabbits; Inage F et al.; The nephrotoxicity of (-)-(S)-9-fluoro-2,3-dihydro-3-methyl-10-(4-methyl-1- piperazinyl)-7-oxo-7H-pyrido {1,2,3-de}{1,4}benzoxazine-6-carboxylic acid hemihydrate (levofloxacin, DR-3355, CAS 100986-85-4), a new quinolone antibacterial agent, was evaluated in male New Zealand White (NZW) rabbits after oral administration of 30 or 120 mg/kg for 10 days . Although reduced body weight gain was observed in the 120 mg/kg, DR-3355 induced no change in function and morphology of the kidneys at both doses.

Arzneimittelforschung, 1992 Mar, 43(3A), 385 - 9
Antigenicity of the new quinolone antibacterial agent levofloxacin; Wagai N et al.; An antigenicity study of a new quinolone antibacterial agent, (-)-(S)-9-fluoro-2,3-dihydro-3-methyl-10-(4-methyl-1-piperazinyl)-7-oxo- 7H-pyrido{1,2,3-de}{1,4}benzoxazine-6-carboxylic acid hemihydrate (lefovloxacin, DR-3355, CAS 100986-85-4), was carried out in mice, guinea pigs and rabbits with passive cutaneous anaphylaxis (PCA), systemic anaphylaxis (SA) and enzyme linked immunosorbent assay (ELISA) . Mice were sensitized with DR-3355 (1-100 mg/kg) or DR-3355-ovalbumin (OA) conjugate (DR-3355-OA; 500 micrograms/kg) . No IgE antibodies to DR-3355 were detected in the sera obtained from the DR-3355-sensitized mice, indicating that DR-3355 has no immunogenicity in mice . By using DR-3355-OA as a sensitizing antigen, DR-3355-specific IgE was produced successfully in 7 out of 10 sera, and 4 sera showed positive responses in 24-h PCA on intravenous injection of DR-3355 (40 mg/kg) . These responses disappeared on challenge with a dose of 2.5 mg/kg . Guinea pigs or rabbits were sensitized with DR-3355 (2-100 or 2-20 mg/kg) or DR-3355-OA (2 mg/kg) . No SA was observed in the sensitized guinea pigs after the intravenous injection of DR-3355 (40 mg/kg) . No antibodies to DR-3355 were detected in the sera obtained from the sensitized guinea pigs and rabbits by PCA or ELISA . These results suggest that DR-3355 may not possess antigenicity in guinea pigs and rabbits . On the other hand, the results of PCA in mice suggest that DR-3355 may have eliciting antigenicity potential.

Arzneimittelforschung, 1992 Mar, 43(3A), 378 - 85
Mutagenicity of the new quinolone antibacterial agent levofloxacin; Shimada H et al.; A new quinolone antibacterial agent (-)-(S)-9-fluoro-2,3-dihydro-3-methyl-10- (4-methyl-1-piperazinyl)-7-oxo-7H-pyrido{1,2,3-de}{1,4}benzoxazine-6- carboxylic acid hemihydrate (levofloxacin, DR-3355, CAS 100986-85-4), was studied for mutagenicity using the following short-term in vitro and in vivo tests . 1 . In vitro studies: reverse mutation test (Ames method) on S . typhimurium and E . coli; and HGPRT forward mutation test, cytogenetic test, and sister chromatid exchange (SCE) test, all on Chinese hamster cells . 2 . In vivo studies: mouse micronucleus test, SCE test on mouse bone marrow cell, in vivo-in vitro unscheduled DNA synthesis (UDS) test on rat primary hepatocytes, and dominant lethal test in BDF1 mice . In the in vitro tests for SCE and for chromosomal aberration, DR-3355 gave dose-dependent positive responses, but no mutagenicity was observed in the same indicators of the in vivo studies, even at the maximum tolerated doses . This strongly suggested that DR-3355 would have no mutagenic effects when used in the treatment of infectious diseases . DR-3355 did not show any positive response in the reverse mutation test, the HGPRT mutation test, the in vivo-in vitro UDS test or the dominant lethal test . These results suggest that chemotherapy with DR-3355 should have no mutagenic effect in man.

Arzneimittelforschung, 1992 Mar, 43(3A), 374 - 7
Reproductive toxicity of the new quinolone antibacterial agent levofloxacin in rats and rabbits; Watanabe T et al.; The reproductive toxicity of (-)-(S)-9-fluoro-2,3-dihydro-3-methyl-10-(4- methyl-1-piperazinyl)-7-oxo-7H-pyrido {1,2,3-de}{1,4}benzoxazine-6-carboxylic acid hemihydrate (levofloxacin, DR-3355, CAS 100986-85-4) was investigated in rats and rabbits . DR-3355 was administered orally prior to and in the early stage of pregnancy to male and female rats at doses of up to 360 mg/kg . No adverse effects on fertility or teratogenicity were noted at any dose . DR-3355 elicited no evidence of teratogenicity when administered during the fetal organogenesis period to pregnant rats at doses of up to 810 mg/kg, or to pregnant rabbits at doses of up to 50 mg/kg . However, female rats receiving 810 mg/kg showed salivation, soiled coats, soft stools and decreases in body weight and food intake . Rat fetuses in the 810 mg/kg group exhibited decreased body weight and retardation of ossification, and showed increases in mortality and skeletal variations . Decreases in maternal body weight and food intake were observed in rabbits in the 50 mg/kg group . No adverse effects were observed in perinatal and postnatal toxicity studies in rats using doses of up to 360 mg/kg.

Arzneimittelforschung, 1992 Mar, 43(3A), 365 - 6
Acute oral toxicity of the new quinolone antibacterial agent levofloxacin in mice, rats and monkeys; Kato M et al.; Acute oral toxicity of (-)-(S)-9-fluoro-2,3-dihydro-3-methyl-10-(4- methyl-1-piperazinyl)-7-oxo-7H-pyrido {1,2,3-de}{1,4}benzoxazine-6-carboxylic acid hemihydrate (levofloxacin, DR-3355, CAS 100986-85-4), a new quinolone antibacterial agent, was studied in ddy mice, SD rats and cynomolgus monkeys . LD50 values were 1,881 mg/kg for males and 1,803 mg/kg for females in mice, 1,478 mg/kg for males and 1,507 mg/kg for females in rats and more than 250 mg/kg in females monkeys . Toxic signs included the decrease in locomotor activity, ptosis, tremor, tonic convulsion and respiratory depressed in rodents and soft feces or vomiting in monkeys . At necropsy, no treatment-related changes were observed in any species except for the enlargement of the cecum in rats.

Drug Saf, 1992 Mar-Apr, 7(2), 116 - 34
Thalidomide in human immunodeficiency virus (HIV) patients . A review of safety considerations; Gunzler V; The sedative thalidomide was withdrawn from the market 30 years ago because of its teratogenic and neurotoxic adverse effects . The compound was later discovered to be extremely effective in the treatment of erythema nodosum leprosum, a complication of lepromatous leprosy . This effect is probably due to a direct influence on the immune system, because thalidomide possesses no antibacterial activity . The compound is presently used as an experimental drug in the treatment of a variety of diseases with an autoimmune character, including recurrent aphthosis of nonviral and nonfungal origin in human immunodeficiency virus (HIV) patients . This article reviews the most important chemical and pharmacokinetic properties of thalidomide . The possible mechanisms of the nonsedative effects of thalidomide with respect to the safety of its use in HIV patients are discussed . Because the mechanism of the immunomodulatory effect of thalidomide is unknown, the possibility that the administration of this compound will accelerate the deterioration of the immunological status of HIV patients cannot be excluded . Clinical evidence suggests that thalidomide may aggravate the condition of patients with preexisting peripheral neuropathy . Hypersensitivity reactions to thalidomide may occur more frequently in HIV patients than in other patient groups . Because of the teratogenic activity of thalidomide, reliable contraception must be provided to female patients of childbearing age . Before the introduction of thalidomide therapy to an HIV patient presenting with oral ulcers, a fungal or viral origin of the lesions should be excluded . Thalidomide should not be used in patients with preexisting HIV-related peripheral polyneuropathy, polyradiculopathy or encephalopathy . In patients experiencing a complete remission, the discontinuation of thalidomide treatment and its reintroduction in the case of a relapse are preferable to maintenance therapy.

J Nat Prod, 1992 Mar, 55(3), 303 - 10
Constituents of Azadirachta indica: isolation and structure elucidation of a new antibacterial tetranortriterpenoid, mahmoodin, and a new protolimonoid, naheedin; Siddiqui S et al.; Mahmoodin {1}, a new limonoid, has been isolated from Azadirachta indica (neem) oil, along with seven known tetranortriterpenoids, azadirone, epoxyazadiradione, nimbin, gedunin, azadiradione, deacetylnimbin, and 17-hydroxyazadiradione . A new protolimonoid, naheedin {3}, has been obtained from the neem fruits along with azadirachtol . Their structures have been elucidated through chemical and spectral analyses including 2D nmr studies . The absolute configuration of 1 was established by comparison of its cd spectrum with those of the known tetranortriterpenoids . Mahmoodin showed significant antibacterial activity against various Gram-positive and Gram-negative organisms . Four hydrocarbons, icosane, docosane, 2-methyltricosane, and docosene, have also been identified by gc-ms of the EtOH extract of the fruit coats . Only docosane has earlier been reported from neem, while the remaining three are unreported from this plant.

Klin Monatsbl Augenheilkd, 1992 Mar, 200(3), 182 - 6
{The effective antibacterial spectrum of sulfacetamide}; Roth HW et al.; Swabs of the anterior eye segment of 180 eyes (145 patients) taken in the time period between August 1, 1989 until August 30, 1989 were sent to an external, independent microbiological institute in order to verify in-vitro antibacterial properties of marketed sulfacetamide containing drugs . MIC test was performed with isolated pathogenic bacterial strains without knowledge of the underlying diagnosis . It was shown that sulfacetamide is able to inhibit the growth of all isolated strains . Depending on the type of bacteria concentrations of 0.006 up to 6.4% sodium sulfacetamide proved to be effective . Simultaneously, all patients were treated with sulfacetamide containing ointment and/or eye drops 4 times daily for maximum of 14 days . With swabs taken at intervals of 7 and 14 days no bacterial growth was detected.

J Antibiot (Tokyo), 1992 Mar, 45(3), 380 - 5
Synthesis and activity of C-21 alkylamino derivatives of (9R)-erythromycylamine; Lartey PA et al.; Novel analogs of (9R)-9-deoxo-9-(N,N-dimethylamino)erythromycin A bearing N-alkylamino substituents at the C-21 position were synthesized . These compounds retained antibacterial activity . The C-21, N,N-dimethylamino analog showed a modest improvement in activity against some Gram-negative bacteria.

Eur Respir J, 1992 Mar, 5(3), 343 - 58
Functions of proteins and lipids in airway secretions; Jacquot J et al.; Proteins and lipids synthesized by airway secretory cells or transudated are active components in the protection of respiratory epithelium . Proteins and ions are involved in the control of mucus hydration . Secretory proteins, such as secretory immunoglobulin A (IgA), transferrin and lysozyme, participate in the airway antibacterial defence . Other biochemical components found in secretions, such as anti-inflammatory and antioxidant agents as well as antiproteases, contribute significantly to the protection of the underlying epithelium.

Lepr Rev, 1992 Mar, 63(1), 41 - 6
Treatment of multibacillary leprosy with a regimen of 13 weeks duration; Pattyn SR et al.; In a prospective study 559 multibacillary patients in Zaire were treated for 13 weeks with twice weekly rifampicin (600 mg) and daily ethionamide (500 mg) and dapsone (100 mg), 13-RED, or clofazimine (100 mg), 13-REC . The patients were followed for a total of 1418 person years, mean 3.2 years . The incidence of hepatitis was 3.3% . The incidence of relapses was 0.28 per 100 person years . Relapses were due to drug-sensitive organisms . In patients who received the same drug regimens but with a reduced dosage of ethionamide to 5 mg/k bodyweight, the incidence of hepatitis was significantly lower but the relapse rate was 7.8 per 100 person years of follow-up in the RED group, no relapses were diagnosed in the REC group . It is concluded that by the use of potent antileprosy drugs in suitable combinations and dosages, it will be possible to shorten the duration of antibacterial treatment in multibacillary leprosy to 3 months.

Gastroenterol Clin North Am, 1992 Mar, 21(1), 257 - 75
Spontaneous bacterial peritonitis; Garcia-Tsao G; SBP is an infection of ascites that occurs in the absence of a local infectious source . It is mainly a complication of cirrhotic ascites, with a prevalence of 15% to 19% (when culture-negative cases are included) . Gram-negative enteric bacteria are the causative agents in more than 70% of cases . SBP is probably the consequence of bacteremia due to defects in the hepatic reticuloendothelial system and in the peripheral destruction of bacteria by neutrophils, with secondary seeding of an ascitic fluid deficient in antibacterial activity . Patients with advanced liver disease and low ascitic fluid protein concentrations seem to have an increased susceptibility to SBP . A diagnostic paracentesis should be performed in any cirrhotic patient who suddenly deteriorates or presents with any compatible symptom of SBP, most frequently fever or abdominal pain, or both . A PMN count greater than 500/mm3 is indicative of SBP, and treatment with intravenous broad-spectrum antibiotics should be initiated immediately . Although the mortality of an acute episode of SBP decreases with early therapy, it is still high (approximately 50%), and patients who survive an episode of SBP have a high frequency of recurrence . Mortality seems to be related to the severity of the underlying liver disease, because only a third of patients die from sepsis and prophylactic antibiotics decrease the frequency of SBP but do not seem to improve long-term survival.

Gut, 1992 Mar, 33(3), 397 - 401
Erythromycin and the gut; Catnach SM et al.; The commonly reported gastrointestinal side effects that occur with erythromycin are related to its prokinetic action on the gut, mediated, at least in part, by its motilin receptor stimulating activity . This action may be of clinical use in conditions associated with gastrointestinal hypomotility such as diabetic gastroparesis and intestinal pseudo-obstruction, although further work needs to be done to establish the long term therapeutic uses of erythromycin in these disorders . Macrolide compounds with no antibacterial properties but which have a pronounced prokinetic action on the gut have already been synthesised and are currently being developed for future use in man . These 'motilides' should provide a useful addition to our rather limited armamentarium of effective gastrointestinal prokinetic agents.

Clin Infect Dis, 1992 Mar, 14 Suppl 1, S154 - 60
Current role of therapy with amphotericin B; Meyer RD; Systemic antifungal chemotherapy frequently is more difficult to conduct than antibacterial therapy . Factors that make it difficult include, but are not limited to, common biosynthetic pathways among the eukaryotes and humans, a relative lack of agents, imprecise modes of use, general lack of standardization of in vitro susceptibility tests that have clinical correlations, and, with certain exceptions, lack of clinical correlations with in vitro results of combination antifungal chemotherapy . Amphotericin B has been available for intravenous administration for greater than 30 years and, despite its shortcomings, remains the drug of choice or reference agent in the therapy for many specific systemic fungal infections in various clinical settings . The current role of amphotericin B therapy in these situations and the need for additional controlled, comparative clinical trials with azoles, liposomal amphotericin B, and amphotericin B complex are discussed.

Minerva Med, 1992 Mar, 83(3), 141 - 4
{Piperacillin: comparison of antibacterial activity in vitro during the triennium 1986-88 versus the biennium 1981-82}; Farris AG et al.; The antibacterial activity in vitro of piperacillin on strains commonly isolated in hospital practice in 1986-88 was compared with that obtained for piperacillin from 1981 to 1982 and with the activity of other antibiotics usually employed . Piperacillin showed a good antibacterial activity on Gram-positive and Gram-negative strains, while few resistant strains were found.

Antibiot Khimioter, 1992 Mar, 37(3), 6 - 9
{A rapid method of evaluation of the effectiveness of antibacterial drugs}; Oborin VA et al.; Efficacy of antibiotics in the treatment of experimental tularemia was studied comparatively on various biological models . It was shown that the antibiotics which proved active against the tularemia microbe in albino mice when studied by the rapid and routine methods were highly efficient in the treatment and prevention of experimental tularemia in rabbits and baboons (hamadryas) . The experiments showed basic possibilities to perform rapid estimation (for at least 2 days) of drug efficacy in experimental glanders and melioidosis in golden hamsters . The rapid method developed by the authors was recommended for the use in primary estimation of the efficacy of new drugs in the treatment of tularemia, glanders and melioidosis.

Jpn J Antibiot, 1992 Mar, 45(3), 285 - 92
{Pharmacokinetic and clinical evaluation of levofloxacin in obstetrical and gynecological field}; Matsuda S et al.; Levofloxacin (LVFX, DR-3355) a new synthetic antibacterial agent, was evaluated pharmacokinetic and clinically in the field of obstetrics and gynecology and the following results were obtained . 1 . The transport of LVFX into genital tissues (various regions in the uterus, ovary and oviduct) after a single oral administration of 200 mg was found to be good . 2 . Sixteen patients with genital infections (endometritis, salpingitis, cervicitis, mastitis) were treated with LVFX at daily doses of 200-300 mg for 5-15 days . The efficacy rate was 100% and no side effect was observed.

Jpn J Antibiot, 1992 Mar, 45(3), 270 - 84
{Pharmacokinetic and clinical evaluation of levofloxacin in obstetrics and gynecology}; Cho N et al.; Levofloxacin (LVFX, DR-3355), a new synthetic quinolone derivative antibacterial agent, was evaluated for its pharmacokinetics and clinical efficacy in obstetric and gynecological infections, and the following results were obtained . Concentrations of LVFX in serum and intrapelvic genital organs such as uterine and adnexal tissues were determined following oral administration of 100 mg . Tissue penetration of LVFX was found to be good, with its tissue levels (Cmax) of 1.17-2.16 micrograms/ml or g after inhalation anaesthesia and 1.15-2.17 micrograms/ml or g after lumbar spinal anaesthesia . LVFX was given to 22 cases of obstetric and gynecological infections with a daily dose of 200-600 mg for 3-14 days and its clinical efficacy was 95% and bacteriological response was 100% . No side effect was observed . From these findings, we consider that LVFX will be a useful antibacterial agent against obstetric and gynecological infections.

Farmaco, 1992 Mar, 47(3), 305 - 18
Synthesis, spectral studies and biological activities of some N-bridged heterocycles derived from 3-arylaminomethyl-4-amino-5-mercapto-1,2,4-triazoles; Holla BS et al.; Synthesis of four 3-arylaminomethyl-4-amino-5-mercapto-1,2,4-triazoles starting from substituted anilines is described . These triazoles were employed in the synthesis of some N-bridged heterocycles carrying arylaminomethyl substituents . All the newly synthesized compounds were characterized by analytical, NMR and mass spectral studies . Some of the newly synthesized compounds were screened for their antibacterial and antiviral properties.

Ann Ital Chir, 1992 Mar-Apr, 63(2), 201 - 7
{Chemotherapeutic prophylaxis in the preparation of the large intestine for surgical interventions: rifaximin P.O . vs . cephalosporin I.V.}; Bresadola F et al.; 30 patients were examined: 17 males and 13 females aged between 53 and 83 years (average age 66 years), candidates for large intestine surgery . For 5 days before the operation, they were treated at random, in a balanced way, with cefotaxime (3 g/day intravenously), either alone or associated with rifaximin (1200 mg/day P.O.) . Rifaximin, an antibiotic drug endowed with a topical intestinal action, substantially increased the antibacterial activity of the well known and traditional third-generation cephalosporins therapy in the prevention of bacterial infections after major colic surgery . Intestinal bacterial load and pathogenic micro-organisms reduction was substantially increased . Furthermore, a more limited onset of post- surgical complications was observed, together with a better post-surgical clinical course, and a more rapid recovery of normal intestinal functions . The possibility of carrying out an effective chemoprophylaxis by means of an oral drug, such as rifaximin, must be encouraged as, among other things, it substantially reduces the intolerance risk at systemic level, which is nevertheless possible with parenteral antibiotic treatments.

Anesteziol Reanimatol, 1992 Mar-Apr, (2), 70 - 1
{A case of successful treatment of a severe form of suppurative meningitis}; Kovrizhnykh NA et al.; A patient with severe meningoencephalitis has been treated using a combination of generalized and local mechanisms of antibacterial drug delivery to the inflammation focus, detoxication and brain circulation improvement . The management results have been analysed . Positive neurological dynamics, homeostasis recovery and shorter period of the patient's stay in an intensive care unit proved the efficacy of management . It is assumed that the improvement of brain perfusion is an important pathophysiological mechanism.

Infection, 1992 Mar-Apr, 20(2), 89 - 93
Pharmacokinetics of rufloxacin once daily in patients with lower respiratory tract infections; Rimoldi R et al.; The pharmacokinetic properties of rufloxacin, a new quinolone antibacterial agent, were evaluated in ten patients with lower respiratory tract infections . Patients were given 400 mg of rufloxacin once a day for seven to nine days . Plasma concentrations of the drug were determined by high-performance liquid chromatography and bioassay at regular intervals during treatment . After the first administration, maximal plasma concentrations were 3.17 +/- 0.36 mg/l (mean +/- SEM) and were reached at 4.2 +/- 0.7 h . At the end of treatment peak plasma concentrations increased to 7.26 +/- 0.52 mg/l . Elimination half-life was 38.2 +/- 2.9 h, with a mean extent of accumulation of 2.96 +/- 0.30 . Treatment was well tolerated, with no abnormalities noted during routine laboratory examinations . Two days after the last administration, measurable levels of rufloxacin were still observed in plasma, indicating that the long half-life of rufloxacin assures valuable antibacterial activity even after discontinuation of treatment.

J Med Chem, 1992 Feb 21, 35(4), 611 - 20
Synthesis and structure-activity relationships of 7-diazabicycloalkylquinolones, including danofloxacin, a new quinolone antibacterial agent for veterinary medicine; McGuirk PR et al.; A series of novel 6-fluoro-7-diazabicycloalkylquinolonecarboxylic acids substituted with various C8 (H, F, Cl, N) and N1 (ethyl, cyclopropyl, vinyl, 2-fluoroethyl, 4-fluorophenyl, 2,4-difluorophenyl) substituents, as well as, 9-fluoro-10-diazabicycloalkylpyridobenzoxazinecarboxylic acids, were prepared and evaluated for antibacterial activity against a range of important veterinary pathogenic bacteria . The diazabicycloalkyl side chains investigated at the 7-position (benzoxazine 10-position) include (1S,4S)-5-methyl-2,5-diazabicyclo{2.2.1}heptane (2), (1S,4S)-2,5-diazabicyclo{2.2.1}heptane (3), (1R,4R)-5-methyl-2,5-diazabicyclo{2.2.1}heptane (4), 8-methyl-3,8-diazabicyclo{3.2.1}octane (5), 9-methyl-3,9-diazabicyclo{4.2.1}nonane (6), 1,4-diazabicyclo{3.2.2}nonane (7), 1,4-diazabicyclo{3.3.1}nonane (8), and 9-methyl-3,9-diazabicyclo{3.3.1}nonane (9) . Among these side chains, in vitro potency was not highly variable; other properties therefore proved more critical to the selection of possible development candidates . However, the relative potencies observed for several of these compounds in mouse, swine, and cattle infection models correlated well with those seen in vitro . A combination of the N1 cyclopropyl group and the C7 (1S,4S)-5-methyl-2,5-diazabicyclo{2.2.1}hept-2-yl appendage conferred the best overall antibacterial, physiochemical, and pharmacodynamic properties . Hence, danofloxacin (Advocin, 2c) (originally CP-76,136, 1-cyclopropyl-6-fluoro-7-{(1S,4S)-5-methyl-2,5-diazabicyclo{2.2.1} hept-2-yl}-1,4-dihydro-4-oxo-3-quinolinecarboxylic acid) was selected as a candidate for development as a therapeutic antibacterial agent for veterinary medicine.

Eur J Biochem, 1992 Feb 15, 204(1), 395 - 9
CecC, a cecropin gene expressed during metamorphosis in Drosophila pupae; Tryselius Y et al.; Cecropins are antibacterial peptides, induced in insects in response to bacterial infections . In Drosophila, three cecropin genes have previously been characterized, CecA1, CecA2, and CecB, in a dense cluster at 99E on the third chromosome . From the same locus, we now describe a fourth member of the cecropin gene family, CecC, which is mainly expressed at the early pupal stage . In situ hybridization to immunized pupae show that CecC is induced in the anterior end of the larval hindgut and in other larval tissues that are undergoing histolysis . Within these other tissues it is often expressed in distinct foci that may correspond to hemocytes . A similar pattern of expression in the metamorphosing pupa is also observed for the CecA and CecB genes . Comparing the DNA sequences of the cecropin genes, a conserved region is observed about 30 bp upstream of the TATA box . It consists of three shorter motifs, two of which are reminiscent of a putative promoter element in immune protein genes from the cecropia moth.

Clin Pharmacokinet, 1992 Feb, 22(2), 132 - 43
Considerations in dosage selection for third generation cephalosporins; Yuk-Choi JH et al.; Pharmacokinetic parameters of third generation cephalosporins vary widely, requiring different dosage regimens and adjustment methods for each agent . Although their antibacterial spectrum favours their usage in infections caused by aerobic Gram-negative organisms, due to their limited post-antibiotic effect against these organisms, dosage regimens should ensure that free drug concentrations at the site of infection remain above the minimum inhibitory concentration for as much of the dosage interval as possible in patients with normal host defence mechanisms and for the entire dosage interval in immunocompromised patients . Altered protein binding encountered in various disease states can affect both microbiological and pharmacokinetic properties especially for drugs with high protein binding . Since the concentrations at the site of action are often different from those in serum, a higher or lower range of dosages needs to be selected depending on the target site . Decreased renal function affects the elimination of most third generation cephalosporins, whereas the presence of hepatic disease does not generally necessitate dosage adjustment . Because of the complex age-related physiological changes in paediatric and elderly patients, dosage should be adjusted on the basis of the reported pharmacokinetic data in these populations . The usual recommended dose may or may not be optimal in a given condition depending on the complex interactions between pharmacokinetic, microbiological and other host factors.

J Med Chem, 1992 Feb 7, 35(3), 518 - 25
Fluoronaphthyridines as antibacterial agents . 4 . Synthesis and structure-activity relationships of 5-substituted-6-fluoro-7-(cycloalkylamino)-1,4-dihydro-4-oxo-1,8- naphthyridine-3-carboxylic acids; Bouzard D et al.; A series of 5-substituted-6-fluoro-7-(cycloalkylamino)-1,4-dihydro-4-oxo-1,8- naphthyridine-3-carboxylic acids have been prepared and tested for their in vitro and in vivo antibacterial activities . The 5-methyl group gave better in vitro activity with the 1-cyclopropyl appendage, but poorer activity with the 1-tert-butyl moiety . With the 1-(2,4-difluorophenyl) substitution, the influence of the 7-cycloalkylamino group was determinant: a (3S)-3-amino-pyrrolidine was shown to enhance greatly the in vitro and in vivo activity of the 5-methyl derivative . Compound 33 (BMY 43748) was selected as a promising candidate for an improved therapeutic agent.

J Med Microbiol, 1992 Feb, 36(2), 78 - 82
Induction of the SOS gene (umuC) by 4-quinolone antibacterial drugs; Power EG et al.; Induction by the 4-quinolone group of antibacterial drugs of the umuC gene, the SOS function most involved in error-prone DNA repair (together with umuD), was assessed in a strain of Escherichia coli harbouring a umuC::lacZ gene fusion . All 4-quinolones tested induced this umuC::lacZ fusion, with maximum induction at 4-quinolone concentrations close to their minimum inhibitory concentrations for this strain, and the SOS Inducing Potential (SOSIP) was closely related to antibacterial activity . Mitomycin C, a known mutagen, was a slightly better inducer (in terms of SOSIP) than any of the quinolones . In contrast, induction by 4-quinolones of the sfiA (sulA) gene, an SOS function involved in cell division inhibition, was better than induction by mitomycin C in an E . coli strain harbouring an sfiA::lacZ gene fusion . The umuC gene fusion was induced at lower concentrations of 4-quinolone than was the sfiA gene fusion.

Pharmazie, 1992 Feb, 47(2), 98 - 101
Mechanism of the polarographic reduction of a new 5-nitrofuran derivative with antibacterial activity; Garcia Monteagudo JC et al.; The reduction at mercury electrodes of a new 5-nitrofuran derivative with antibacterial activity, N2-(5-nitrofurfurylidene)formohydrazide-4-(3,5-dicyanophenyl)-6-ethoxy-2- pyridyl)imide, was studied by conventional, normal pulse, reverse normal pulse and differential pulse polarography in water-dimethylformamide (30%) buffered media . The waves observed, whose number depended on pH, are attributed to the reduction of the nitro group (6 electrons) and the azomethinic unit (4 electrons) . The basic mechanisms of the electrode reactions have been deduced from the characteristics of the waves . Conditions for determining the formal potential of the nitroderivative/radical-anion system, a parameter related to pharmacological activity, are also reported.

J Nat Prod, 1992 Feb, 55(2), 225 - 8
Isolation, NMR studies, and biological activities of onopordopicrin from Centaurea sonchifolia; Lonergan G et al.; A sesquiterpene lactone, onopordopicrin {1}, has been isolated from Centaurea sonchifolia . Its structure was established by 2D nmr (1H-1H and 13C-1H correlations), and the conformation in CHCl3 was examined by nOe studies . Cytotoxic, antibacterial, and antifungal activities are reported.

J Nat Prod, 1992 Feb, 55(2), 174 - 8
Four new antibacterial sesterterpenes from a marine sponge of the genus Luffariella; Konig GM et al.; The structures of four new sesterterpenoid compounds 1-4 isolated from a marine sponge of the genus Luffariella, collected from The Great Barrier Reef, Australia, have been determined by analysis of their 1H-nmr, 13C-nmr, ir, uv, and eims spectral data . The new metabolites 1-4 were found to co-occur with the compounds manoalide, secomanoalide, Z-neomanolaide {5}, and E-neomanoalide.

Indian Pediatr, 1992 Feb, 29(2), 181 - 8
Adverse drug reaction monitoring of ciprofloxacin in pediatric practice; Karande SC et al.; Ciprofloxacin, a fluoroquinolone antibacterial agent, is not recommended in pediatric population on account of its possible adverse effect on growing cartilage . It is being commonly used for treatment of variety of infections in children in our country and very little information is available on the risks involved in its use . A questionnaire was sent to 750 pediatricians in the last week of November 1990, to retrospectively judge over the previous 2 month period the extent of its use and identify the adverse drug reactions (ADRs) . One hundred and fifty-four pediatricians replied, of which 147 had prescribed ciprofloxacin in a total of 3341 patients under 18 years of age, enteric fever being the commonest indication for its use . One hundred and fifty-nine ADRs were reported in 104 (3.1%) patients . They were: gastrointestinal in 50% of these 104 patients, CNS in 23%, skin and allergic in 19.1%, musculoskeletal in 8.6%, hematological in 3.8%, CVS in 2.9% and nephrological in 0.9% cases . Of 159 ADRs, 8 (5%) were severe, 76 (47.8%) were moderate and 75 (47.2%) were mild . Therapy needed discontinuation in only 9 (0.3%) patients . Two new ADRs were identified, viz., sudden death after intravenous ciprofloxacin and sinus nodal arrest causing bradycardia.

J Appl Bacteriol, 1992 Feb, 72(2), 146 - 53
Studies on the lactoperoxidase system: reaction kinetics and antibacterial activity using two methods for hydrogen peroxide generation; Dionysius DA et al.; Components of the lactoperoxidase system were measured during incubation in Isosensitest broth, with enzymatic (glucose oxidase, GO) or chemical (sodium carbonate peroxyhydrate, SCP) means to generate H2O2 . When low levels of thiocyanate (SCN-) were used in the GO system, H2O2 was detected and lactoperoxidase (LP) was inactivated when SCN- was depleted . With 10-fold higher SCN-, LP remained active and H2O2 was not detectable . The oxidation product of the LP reaction, most likely hypothiocyanite, was present in low concentrations . When SCP was used for the immediate generation of H2O2 in a system employing low SCN-, half the LP activity was lost within minutes but thereafter it remained stable . Low concentrations of oxidation product were measured and H2O2 was not detected during the course of the experiment . At high SCN- levels, relatively high concentrations of oxidation product were produced immediately, with H2O2 undetectable . The results suggest that the final product of the LP reaction depends on the method of H2O2 generation and the relative proportions of the substrates . Antibacterial activity of the two LPS was tested against an enterotoxigenic strain of Escherichia coli . Both systems showed bactericidal activity within 4 h incubation at 37 degrees C.

J Antibiot (Tokyo), 1992 Feb, 45(2), 240 - 5
The synthesis, antibacterial, and beta-lactamase inhibitory activity of a novel asparenomycin analog; Bouthillier G et al.; An analog, 6-(2'-hydroxyethylidene)-4 beta-methyl-1-azabicyclo{3.2.0}hept-2-ene-2- carboxylate (11), of the carbapenem beta-lactamase inhibitor, asparenomycin A, was synthesized . It possessed a spectrum of antibacterial activity that was comparable to that of asparenomycin A but was less effective as a beta-lactamase inhibitor . With ampicillin, it only exhibited a moderate level of synergy against a variety of beta-lactamase-producing organisms . Although the presence of a 4 beta-methyl group in the analog brought about a significant increase in chemical stability relative to that of asparenomycin A, it did not result in an increase in stability to kidney dehydropeptidase enzyme.

J Antibiot (Tokyo), 1992 Feb, 45(2), 227 - 34
Transformation of streptonigrin into streptonigrone; synthesis and biological evaluation of antibiotics streptonigrin and streptonigrone alkyl ethers; Preobrazhenskaya MN et al.; A method of synthesis of antibiotic streptonigrin 8'-O-alkyl ethers by alkylation of streptonigrin diphenylmethyl ester and consequent deprotection of carboxylic group with CF3COOH is developed . An attempt to deblock carboxylic group of 8'-O-methylstreptonigrin diphenylmethyl ester by hydrogenation over Pd produced 8'-O-methylstreptonigrone . Similarly streptonigrin was transformed into streptonigrone over Pd-black in H2 stream . Methylation of streptonigrone afforded 5',5'-N-dimethyl-2',8'-O-dimethylstreptonigrone and 1',5',5'-tri-N-trimethyl-8'-O-methylstreptonigrone . Alkyl streptonigrin ethers demonstrated lower antibacterial activity in vitro than the parent antibiotic.

J Antibiot (Tokyo), 1992 Feb, 45(2), 213 - 26
N-acyl 3-alkylidenyl- and 3-alkyl azetidin-2-ones: a new class of monocyclic beta-lactam antibacterial agents . 1 . Structure-activity relationships of 3-isopropylidene and 3-isopropyl analogs; Brickner SJ et al.; The synthesis and antibacterial activity of a series of N-acyl 3-isopropylidenyl- and 3-isopropyl 2-azetidinones having potent in vitro antibacterial activity, particularly against anaerobic organisms, is described . A distinguishing structural feature of these compounds is the lack of any ionizable moiety appendant to the lactam nitrogen.

Ophthalmology, 1992 Feb, 99(2), 192 - 6
Medical management of ocular malakoplakia; Simpson C et al.; A 14-year-old girl had a granulomatous conjunctival lesion, proven histologically to be malakoplakia . This is the first reported case of malakoplakia arising from conjunctiva, although three others have involved the ocular adnexa . Malakoplakia is a rare disease often associated with immunodeficiency and is characterized by the presence of intracellular inclusions and organisms due to deficient intracellular bacteriolysis . Medical management is difficult because an effective antibacterial agent requires three properties: activity against the organism involved, good intracellular penetration, and the capacity to maintain its effectiveness in the intracellular milieu . Escherichia coli was isolated from a biopsy specimen and from conjunctival swabs . Treatment with systemic ciprofloxacin, which has good intracellular penetration and activity, led to rapid resolution of the lesion . This is the first report concerning the successful use of this drug to treat malakoplakia of any organ.

J Am Vet Med Assoc, 1992 Feb 1, 200(3), 366 - 7
Epistaxis in two horses with dacryohemorrhea; Schumacher J et al.; Unilateral epistaxis in 2 horses was caused by inflammation of the distal portion of the lacrimal system . The origin of epistaxis was identified during physical examination by observing hemorrhage emanating from the nasal opening of the nasolacrimal duct . Dacryohemorrhea caused by bacterial infection was successfully treated with antibacterial drugs administered systemically and instilled into the lacrimal system.

Am J Obstet Gynecol, 1992 Feb, 166(2), 606 - 12
Direct inhibition of proteases and cervical plasminogen activator by antibiotics; Milwidsky A et al.; OBJECTIVES: Preterm premature rupture of the fetal membranes and premature delivery are sometimes linked to genital tract infection and activation of proteolytic enzymes that degrade the extracellular matrix . The possible beneficial effect of antibiotics in prevention of preterm premature rupture of fetal membranes and retardation of the onset of labor in some patients with clinical or subclinical infection was explained via their antibacterial efficacy . The aim of this study was to determine the effect of antibiotics on proteolytic enzymes as a possible explanation for the ability of antibiotics to retard preterm labor . STUDY DESIGN: The direct effect of four antibiotics on the proteolytic activities of purified collagenase, elastase, plasmin, trypsin, and chymotrypsin and on streptokinase and human cervical plasminogen activator was measured . RESULTS: The macrolide antibiotic erythromycin and the beta-lactam antibiotics penicillin G, cloxacillin, and ampicillin exerted, in most of the tested combinations with the different proteases, inhibitory effects on the proteolytic activities . CONCLUSION: The present finding that antibiotics directly inhibit proteases may offer an explanation for the beneficial response to antibiotic therapy in some cases of idiopathic preterm labor even in absence of pathogenic bacterial infection.

Khirurgiia (Mosk), 1992 Feb, (2), 67 - 70
{The treatment of unformed intestinal fistulae}; Petrenko TF et al.; Experience in the treatment of 33 patients with unformed intestinal fistulas is discussed . The choice of the method for surgical management was determined by the localization of the fistulas, the possibility of their occlusion, and the severity of the patient's condition . Complex therapy included selective administration of antibacterial agents and extracorporeal detoxification by means of biohemosorption . Rational surgical tactics and complex treatment including extracorporeal detoxification in patients with unformed external intestinal fistulas made it possible to reduce the mortality rate from 33.4% to 21.2% (7 patients died).

J Antimicrob Chemother, 1992 Feb, 29(2), 207 - 17
A comparison of the costs of ceftazidime therapy and gentamicin combinations in three UK hospitals; Malek M et al.; This study compares the utilization costs of ceftazidime therapy with those of gentamicin in combination with other antibacterial drugs . The results show that the relatively high purchase cost of ceftazidime compared to combinations is more than counterbalanced by the additional materials used for drug administration and serum antibiotic assays, even when other drugs were combined with ceftazidime . The average drug and equipment costs were 230.13 pounds for ceftazidime regimens and 253.94 pounds for gentamicin regimens . It is also shown that ceftazidime therapy is associated with a reduction in personnel time compared to gentamicin regimens . The average times per patient for administration and assay were 1 h 43 min for ceftazidime and 4 h 57 min for gentamicin regimens . We conclude that ceftazidime regimens are cheaper than gentamicin regimens when all drug and equipment costs are quantified . Moreover, the use of ceftazidime will release staff time for other purposes.

Can J Microbiol, 1992 Feb, 38(2), 115 - 23
Mode of antibacterial action of dodine (dodecylguanidine monoacetate) in Pseudomonas syringae; Cabral JP; Treatment of Pseudomonas syringae cells with 50 microM dodecylguanidine monoacetate (dodine) resulted in the rapid degradation and release of RNA and cell lysis . Higher concentrations resulted in a progressive decrease in the intensity of these responses, and the appearance of extensive zones of coagulated cytoplasm, indicating that the decrease in RNA degradation probably resulted from an inhibition of the RNases, due to protein denaturation . Dodine also induced expansion of the outer membrane, with the formation of protuberances and intracellular myelin-like structures, which were already evident after 1 min of treatment, indicating that dodine is able to cross the outer and cytoplasmic membranes rather rapidly, and to form, alone or in combination with cell phospholipids and proteins, considerable amounts of triple-layered profiles . In P . syringae cells, saturation levels of dodine corresponded to more than five times the amount needed to form a close-packed monolayer of dodine on the cell surface . The different membranous structures formed in dodine-treated cells, and the coagulation of the cytoplasm, seem to be responsible for the uptake of such high amounts of dodine . The uptake isotherm was essentially Langmuirian . The results presented in this and previous reports indicate that the antibacterial activity of dodine on P . syringae is mainly the result of the action of micelles of the surfactant.

Clin Infect Dis, 1992 Feb, 14(2), 608 - 15
Cytomegalovirus infection in patients with AIDS; Drew WL; Advances in the field of antiviral therapy are now occurring with increasing frequency and rapidity and often generate varying degrees of confusion among those of us whose practices are focused primarily on therapy with antibacterial agents . How to treat cytomegalovirus infections in patients infected with the human immunodeficiency virus constitutes one of the best examples of the quandaries engendered by these advances, and the topic is reviewed in this first AIDS Commentary update . Given the U.S . Food and Drug Administration's recent approval of foscarnet, this discussion is very timely; it is particularly relevant for clinicians to be made aware of current lines of thought regarding induction versus maintenance therapy, the benefits of efficacy versus adverse effects of drug-related toxicity, and the interactions between antiretroviral drugs and ganciclovir or foscarnet . Dr . W . Lawrence Drew's career in this area has been long-standing and productive, and he is one of the leading experts in the field . In this update he addresses these perplexing issues.

FEBS Lett, 1992 Jan 20, 296(2), 190 - 4
Shortened cecropin A-melittin hybrids . Significant size reduction retains potent antibiotic activity; Andreu D et al.; We have earlier reported two 26-residue antibacterial peptides made up from different segments of cecropin A (CA) and melittin (M) . We now report a substantial reduction in size at the C-terminal section of the highly active hybrid CA(1-8)M(1-18), leading to a series of 20-, 18- and 15-residue analogs with antibiotic properties similar to the larger molecule . In particular, the 15-residue hybrids CA(1-7)M(2-9), CA(1-7)M(4-11) and CA(1-7)M(5-12) are the shortest cecropin-based peptide antibiotics described so far, with antibacterial activity and spectra similar or better than cecropin A and a 60% reduction in size . Their reduced size and highly alpha-helical structure require an alternative mechanism for their interaction with bacterial membranes.

J Pediatr, 1992 Jan, 120(1), 72 - 7
Measuring the comparative efficacy of antibacterial agents for acute otitis media: the "Pollyanna phenomenon"; Marchant CD et al.; In randomized, double-blind trials of antibiotic therapy for acute otitis media that determined both clinical and bacteriologic outcomes, clinical success rates were (93%) 236 of 253 for patients with bacteriologic success, (62%) 25 of 40 for those with bacteriologic failure, and (80%) 124 of 155 for those with nonbacterial acute otitis media . These rates were used to calculate the effectiveness of three strategies for assessing drug efficacy: (1) tympanocentesis and culture before and during therapy (bacteriologic efficacy), (2) tympanocentesis before therapy and assessment of clinical efficacy in bacterial acute otitis media, and (3) no tympanocentesis and assessment of clinical efficacy in clinical (total) acute otitis media . For a drug with a bacteriologic efficacy of 100%, calculated clinical efficacy was 93% for bacterial acute otitis media and 89% for clinical acute otitis media . For a drug with bacteriologic efficacy of 27%, a rate consistent with no antibacterial therapy, efficacy was 71% for bacterial acute otitis media and 74% for clinical acute otitis media . We conclude that if efficacy is measured by symptomatic response, drugs with excellent antibacterial activity will appear less efficacious than they really are and drugs with poor antibacterial activity will appear more efficacious than they really are . The predominant phenomenon is that drugs with poor antibacterial activity will appear to be clinically effective in the treatment of acute otitis media.

J Infect Dis, 1992 Jan, 165(1), 34 - 45
Antibacterial and protective properties of monoclonal antibodies reactive with Escherichia coli O111:B4 lipopolysaccharide: relation to antibody isotype and complement-fixing activity; Oishi K et al.; In vitro and in vivo antibacterial and protective properties of murine monoclonal antibodies (MAbs) to Escherichia coli O111:B4 lipopolysaccharide (LPS) were evaluated in relation to antibody isotype and complement-fixing activity . Six O side chain-specific MAbs, including two IgMs and one of each IgG subclass, were analyzed for quantitative binding and C3 deposition on intact bacteria, complement-mediated bactericidal and opsonophagocytic activity, and protection against intraperitoneal infections in mice . Although C3 was deposited on bacteria in the presence of normal human serum (NHS) alone, LPS-specific MAbs increased C3 attachment in a dose-dependent manner . Bacterial killing occurred only in the presence of both antibody and complement NHS and required an intact alternative pathway . The efficiency of bacterial killing varied by antibody isotype (IgM greater than IgG2a greater than other IgG subclasses) and correlated with C3-fixing capacity . Opsonophagocytic activity of MAbs exhibited a similar isotype-related rank order . Likewise, IgM was more active than IgG, and IgG2a was superior to other IgG subclasses, in MAb-mediated protection against intraperitoneal infection . These data document the interdependent antibacterial and complement-fixing properties of LPS-reactive MAbs and the degree to which both activities are determined by antibody class and isotype.

Ross Med Zh, 1992, (2), 6 - 8
{Ventricular ejection fraction in oxygen therapy of patients with pulmonary tuberculosis}; Ershov AI et al.; Radionuclide study of ejection fraction of the right heart ventricle was carried out in lung tuberculosis patients with respiratory insufficiency and cor pulmonale . Oxygen therapy was found to promote reduction of right ventricle heart failure in effective treatment of lung tuberculosis . The greatest reduction of heart failure was recorded in cases where oxygen therapy was combined with cardiac glycosides . As the tuberculosis process progresses, oxygen therapy does not decrease right ventricle heart failure . The treatment by antibacterial agents alone without using oxygen does not lead to the rise of ejection fraction of the right ventricle of the heart.

Vet Med (Praha), 1992 Jan, 37(1), 21 - 31
{Tests of Milkofix, a new preservative preparation for milk samples used for infrared analysis of milk components . I . Verification of its bacteriostatic and bacteriocidal effects and its interference effects}; Hanus O et al.; Hygienic, ecological and health problems of sample preservation for an analysis of basic milk components make us continually to develop a safer chemical preservative substance which will preserve the original sample composition for the time required and which will not influence the analyses . Trzicky (1990) proposed Milkofix (M), a preservative substance on the basis of silver compound . The author reports on minimum risks of the use of this preparation, in comparison with traditional preservatives . Preservative efficiency of Milkofix was compared with other preservatives: K2Cr2O7 (C), NaN3 (A) and bronopol (B) . The following concentrations were used: A--0.0085 g NaN3 and 0.0630 g NaCl, B--0.0050 g bronopol and 0.0500 g NaCl, C--0.0330 g K2Cr2O7 and 0.0670 g KCl in tablet, M--0.1250 g of the mixture, all amounts are per 25 ml milk . The observed antibacterial efficiency of M could be seen in a slower decrease in actual acidity, and/or in an increase in titratable acidity in M-treated samples unlike untreated ones (N) . From the starting value pH 6.3 (Fig . 1), the value of N treatment dropped to 3.8 after two days, the values of M and A treatments dropped to 4.9 after nine days and to 5.7 after twelve days, respectively . As for SH, the values increased within the same interval from 6.5 (2.5 mmol/l) to 28.6 in N, and to 22.3 in M and 9.4 in A (Fig . 3) . There was a similar trend when the milk samples were stored at a temperature of 4 degrees C, but the differences between the preservation methods were not so clear in comparison with storage at a temperature of 20 degrees C (Figs . 1 and 3) . The standardized SH value of 9.0 (2.5 mmol) for infraanalyzer measurements was exceeded after 24 hours in N samples, after four days in M samples and after 12 days in A samples at a temperature of 20 degrees C . The observation of the growth of microorganism counts (CPM) showed that this growth was slower in M than in N, but faster in the samples of C treatment (Fig . 5) . The generative time of CPM in N made 1.6 hours, in M 2.4 hours and in C 7.9 hours . The lag phase of these mixed cultures was 24 hours in M, 60 hours in C and in N treatment the lag phase was zero.(ABSTRACT TRUNCATED AT 400 WORDS)

Klin Khir, 1992, (4), 1 - 4
{Antibacterial and immunocorrective therapy of diffuse purulent peritonitis}; Zaitsev VT et al.; The effectiveness of surgical treatment of 193 patients with generalized purulent peritonitis was analysed . The complex of bacteriologic and immunologic investigations contributed to optimization of antibacterial and immunocorrective therapy . Rational antibacterial therapy should be based on the principle of the use of broad and super-broad spectrum antibiotics with mandatory inclusion into the programme for treatment of metronidazole, administration of antibacterial agents before, at the time and after the operative intervention before identification of microflora and determination of its sensitivity to antibiotics . The therapeutic and tactical approach developed permitted to reduce lethality in generalized purulent peritonitis from 39.5 to 24.9%.

Respiration, 1992, 59(2), 116 - 8
Wegener's granulomatosis--treatment under revision?
Puolijoki H, Liippo K, Raitio M, Tala E.
A 44-year-old man with nasal and respiratory symptoms combined with positive serum antibodies to neutrophil cytoplasmic antigens (ANCA) suggestive of Wegener's granulomatosis was treated with antibacterial agents . Complete clinical response was achieved with co-trimoxazole, and the titer of ANCA declined . After a 12-month treatment period, the patient contracted fever and respiratory symptoms and fatigue again, and he had proteinuria and hematuria . After the institution of conventional treatment with oral prednisolone and cyclophosphamide, a favorable response was achieved . Wegener's-like granulomatosis is difficult to diagnose at its early stage, but the presence of ANCA may be helpful . We suggest that co-trimoxazole should be considered as a first-line treatment, under careful supervision, for young patients whose disease is limited to the respiratory organ.

Chemotherapy, 1992, 38(1), 1 - 6
Oral disposition kinetics of ofloxacin in patients with compensated liver cirrhosis; Orlando R et al.; The disposition kinetics of ofloxacin, a quinolone antibacterial agent excreted essentially unmodified by the kidney, was studied after single oral administration in 8 patients with compensated liver cirrhosis and in 8 control subjects . Mean elimination half-life and apparent volume of distribution were significantly increased in the cirrhotic group (7.6 vs . 4.9 h and 1.6 vs . 1.2 liters kg-1, respectively) . A reduction in the renal clearance of ofloxacin was also observed in the cirrhotic patients, in spite of an apparently normal renal function . These observations indicate that also the pharmacokinetics of unmetabolized drugs may be altered in compensated liver cirrhosis . The serum concentration-time profiles of nearly all subjects exhibited a secondary peak 4-6 h after dosing . This double-peak behavior was interpreted as either enterohepatic circulation or biphasic gastric emptying of ofloxacin.

Probl Tuberk, 1992, (1-2), 8 - 10
{Biochemical mechanisms of neurotoxic reactions to antibacterial preparations in patients with pulmonary tuberculosis}; Chelnokova NV et al.; Examination comprising the electrophysiologic method and study of the biochemical parameters of the antioxidant/lipid peroxidation system and metabolism of biologic amines in 163 patients with infiltrative pulmonary tuberculosis has revealed a clear interaction existing between the functional changes of the CNS state, the state of antioxidative defense (alpha-tocopherol) and serotonin . This allows an assumption that the antioxidant/lipid peroxidation system and serotoninergic system actively participate in the pathogenesis of development of neurotoxic reactions to antibacterial preparations in the clinical picture of tuberculosis.

Pediatr Res, 1992 Jan, 31(1), 18 - 21
Defective production of interleukin-6 by monocytes: a possible mechanism underlying several host defense deficiencies of neonates; Schibler KR et al.; Several deficiencies in antibacterial defense have been described in neonates . Among those best characterized are delayed maturation of B cells into antibody producing cells, deficient T-cell maturation, and delayed cycling of hematopoietic progenitor cells after an infectious challenge . No unifying theory has been forwarded, however, to explain the concomitance of these three developmental deficiencies . IL-6, a cytokine produced primarily by monocytes and macrophages in response to stimulation by IL-1, is involved in the regulation of these three processes . Thus, we postulated that defective production of IL-6 could be a mechanism underlying these immune deficiencies of neonates . Indeed, we observed that a peak production, cells of five term neonates produced only one half as much IL-6 (14 120 +/- 2590 pg IL-6/10(6) monocytes) as those of five adults (28 940 +/- 1680 pg, p less than 0.001) . Peak production was lower still by monocytes of six preterm neonates (7190 +/- 1400 pg, p less than 0.001 versus term) . Production of IL-6 protein was inhibited by actinomycin D and the IL-6 mRNA content of monocytes from neonates, as assessed by competitive polymerase chain reaction, was less than that of adult monocytes . We speculate that defective IL-6 transcription might underlie some of the defects in immune regulation observed in neonates.

Grud Serdechnososudistaia Khir, 1992, (1-2), 21 - 3
{Antibacterial prophylaxis in heart surgery interventions with extracorporeal circulation}; Gel'fand BR et al.; Clinico-laboratory studies were conducted in 30 patients who underwent operations for heart diseases and thromboembolism of the pulmonary artery under extracorporeal circulation . Gentamicin and tobramycin were used for antibacterial prophylaxis . Study of the pharmacokinetics of the agents disclosed essential changes of the distribution volume and clearance of the antibiotics in the patients of the studied group, which made the routine regimen of their administration modified . Analysis of the results of administration of the agents according to a modulatory regimen showed its high prophylactic efficacy in the absence of side effects.

Klin Khir, 1992, (1), 38 - 40
{Combined antibacterial therapy in acute lactation mastitis}; Bondarev VI et al.; The results of treatment of 129 patients with acute suppurative lactic mastitis are presented . In severe forms of the disease, the use of combined antibiotic therapy+ permits to shorten the duration of in-patient treatment from 13.5 to 10.3 days, prevent the disease recurrence.

Eur J Clin Microbiol Infect Dis, 1992 Jan, 11(1), 51 - 4
Susceptibility of Mycobacterium kansasii to ethambutol and its combination with rifamycins, ciprofloxacin and isoniazid; Hjelm U et al.; The susceptibility of Mycobacterium kansasii to antibacterial agents alone and in combination was studied . Widespread resistance to ethambutol, ciprofloxacin and isoniazid was found when these drugs were tested separately . However, pronounced antibacterial effects were seen when ethambutol was tested in combination with ciprofloxacin, rifampicin or rifabutin, which corresponded to significantly decreased resistance to these drugs in combination.

C R Acad Sci III, 1992, 314(2), 43 - 8
{Antibacterial resistance induced by injection of ascitic fluid (with IgM partially removed) and natural monoclonal antibodies of human origin in rainbow trout}; Michel C et al.; Human monoclonal immunoglobulins M from myeloma shown to have the typical polyspecificity of natural antibodies, were precipitated from the ascitic fluid that originally contained them . The IgM and their supernatant were injected in parallel, intraperitoneally into rainbow trout (Oncorhynchus mykiss) to test passive protection against experimental furunculosis . Protection was observed in both cases (significant protection at 2%) . However, only trout treated with IgM were still protected against polybacterial cross-infections which occurred 10 days later (significant protection at 1%) . These results confirm the passive mammalian protection conferred by biologic fluids injected in vivo in fish and provide further evidence for participation of natural antibodies in antibacterial defences.

J Periodontol, 1992 Jan, 63(1), 2 - 6
Intrapocket chemotherapy in adult periodontitis using a new controlled-release insert containing ofloxacin (PT-01); Yamagami H et al.; PT-01 is a newly developed water-soluble controlled-release insert containing ofloxacin (OFLX) as an antibacterial agent . The effect of PT-01 was evaluated by split-mouth application after oral hygiene instruction . No mechanical debridement was carried out during the experiment . PT-01 was applied once a week for 4 weeks in the periodontal pockets of 46 patients with adult periodontitis . The control insert without any antibacterial agent was applied in a selected pocket in a different quadrant for each patient . Clinical findings plaque index, PI; gingival index, GI; bleeding on probing, BOP; pus discharge, pus; and probing depth, PD at both PT-01 and control sites were measured at every visit for 4 weeks . Clinical findings were improved at both PT-01 and control sites, but the improvements were much more significant at PT-01 sites, in particular BOP and PD, than at control sites . PI was also significantly reduced at PT-01 sites . These results suggest that weekly application of PT-01 in the periodontal pocket has a significant effect on the resolution of periodontal inflammation and has an inhibitory effect on supragingival plaque deposition.

Antibiot Khimioter, 1992 Jan, 37(1), 39 - 41
{Prolonged antibacterial action of synthetic suture materials containing gentamicin}; Klimenkov AA et al.; A new sutural material in the form of polyacrylamide threads containing gentamicin in an amount of 10 per cent by the thread weight was studied . After storage for a year under refrigerator conditions the threads preserved their antibacterial activity when studied in vitro . Since gentamicin was included within the threads by means of the ionic links its release from the threads to the environment either in vitro or in vivo was gradual and uniform within at least 10 days . The quantity of the released antibiotic depended on its content per unit of thread length . The marked antibacterial effect within the prolonged period is a basis for the use of the threads in surgical practice for the prevention of infections in the early postoperative period.

Probl Tuberk, 1992, (3-4), 33 - 6
{Anthelmintic therapy of opisthorchiasis in patients with active tuberculosis}; Kashuba EA et al.; Study was based on the clinical and laboratory follow up of 34 patients with active pulmonary tuberculosis in 12 of whom it was concurrent with opisthorchiasis . The clinical course of the combined pathology and immunopathogenesis were evaluated by the monocytic interleukin-1 capacity to regulate the immune T-system status . In conditions when the course of tuberculosis is aggravated by opisthorchiasis invasion, the number of cases of antibacterial therapy intolerance increases and prognosis of the diseases deteriorates, it is expedient to use the anthelminthic therapy with a new preparation biltricide which also has an immunomodulating action . It was shown that the antibacterial and anthelminthic therapy had a favourable clinical and immunologic effect.

Probl Tuberk, 1992, (3-4), 28 - 30
{Effectiveness of the treatment of spontaneous pneumothorax complicating tuberculosis and other lung diseases}; Maksumov KM et al.; The paper deals with the data of the clinical follow up observation and treatment of 186 patients with various clinical forms of tuberculosis and nonspecific pulmonary diseases complicated by spontaneous pneumothorax (SP) . Treatment was composed of etiotropic, antibacterial, general invigorating and symptomatic measures and correction of the protein and volemic disorders . Local treatment was started with puncture of the pleural cavity . Drainage was applied after 2-3 punctures failed to bring lung expansion . Other measures included persistent aspiration, regular washing of the pleural cavity and administration of antibiotics . Punctures resulted in cure of 8.5% and drainage of 43.1% of the patients . Ineffective drainage was considered as an indication to radical interventions . In the presence of lung inflammation or pleural empyema operations were performed when these conditions underwent regress or stabilization . Treatment effectiveness constituted 63.4%, improvement 17.1%, conditions without changes 5.4% and mortality 8.1% of the cases . In benign SP all patients were cured; in development of pneumothorax and pleural empyema treatment effectiveness was 63.9% and mortality 9.4% . SP cure in pulmonary tuberculosis was 56.7%, mortality 12.4%; in nonspecific pathology the values were 89.2 and 6.8%, respectively.

Infection, 1992, 20 Suppl 1, S51 - 3
Cefodizime host-defence enhancement: considerations of dose-response relationships in healthy volunteers; Gialdroni Grassi G et al.; Studies with cefodizime in animals have shown that this new aminothiazolyl cephalosporin, possessing a broad antibacterial spectrum, positively influences a number of immunological parameters . In most investigations in which different dosage regimens were compared, a bell-shaped dose-response relationship was determined, i.e . activity after higher doses returned to near-baseline levels . This finding is typical of most immunomodulating agents . On this basis, the results obtained in healthy subjects were reviewed . Studies for investigating the biological response modifying (BRM) properties of cefodizime have been conducted in this population with either 2 g once daily i.v . or--in the majority--with 2 x 2 g/day i.v . After seven days of treatment with 1 x 2 g daily, no relevant changes could be demonstrated in healthy subjects, whereas there was an increase in monocyte and granulocyte chemotaxis in a parallel group of patients with multiple myeloma . In contrast, treatment with 2 x 2 g daily induced higher lymphocyte responsiveness and significantly increased nonspecific phagocytosis of both neutrophils and monocytes . The experience in healthy volunteers clearly demonstrates that the latter dose, usually the highest required for antibiotic treatment with cefodizime, is still located on the upward slope of the dose-response curve of positive BRM effects.

Clin Ter, 1992 Jan, 140(1), 33 - 41
{The clinical and immunological efficacy of a combination of immunoglobulins and an oral polyvalent antibacterial vaccine in recurrent respiratory infections}; Guerra E et al.; Ninety patients with a history of recurrent upper and lower respiratory infections were randomized into three groups of 30 patients each . Group 1 was treated with i.m . immunoglobulins and oral polyvalent bacterial vaccine, group 2 with vaccine only, while group 3 was not submitted to prophylactic treatment . During and after prophylaxis, all three groups were evaluated for frequency of recurrent respiratory infections and the most relevant immunological parameters . In groups 1 and 2, a significant reduction of minor and major upper and lower respiratory infections was observed compared to the control group . Patients treated with Ig+vaccine or vaccine alone showed an increase of IgG2 subclasses and CD4 lymphocytes and positive changes of delayed skin tests . These findings confirm the results of previous preliminary studies which had shown the polyvalent bacterial vaccine to be useful for the reduction of recurrent infections of the respiratory tract, especially during the winter . Further studies will have to be carried out in order to identify the precise mechanism by which antigen stimulation with the oral vaccine improves the immunological response of the respiratory tract.

Ter Arkh, 1992, 64(1), 71 - 5
{The role of the polyclinic in raising the efficacy of rehabilitation with peptic ulcer patients}; Grigor'ev PIa et al.; The authors provide the results of the treatment and prophylaxis of peptic ulcer (PU) patients followed up by the polyclinic for 14 years . On a large factual material they estimate the efficacy of PU patients treatment with the use of drugs belonging to different groups, including drugs that exert antisecretory, cytoprotective and antibacterial effects . During the follow-up period, the number of patients with medium-grave and grave PU decreased whereas that of patients with mild disease and no relapses rose for 4-5 years and over (from 4.8% in 1972 to 39.6% in 1989) . It has been established that the efficacy of rehabilitation measures for PU is determined by a lot of factors, first of all by adequate drug therapy with the use of the novel pharmacological preparations: selective blockers of histamine H2-receptors (ranitidine, famotidine), colloidal bismuth subcitrate (de-nol) that exert a cytoprotective and antibacterial action on Helicobacter pylori . The combination of the indicated remedies with antibacterial drugs (trichopol, oxacillin, furazolidon) for the treatment of PU relapses and their prevention is based.

Arch Microbiol, 1992, 157(5), 406 - 10
Biological effects of tolytoxin (6-hydroxy-7-O-methyl-scytophycin b), a potent bioactive metabolite from cyanobacteria; Patterson GM et al.; Tolytoxin, a macrocyclic lactone, is a potent antifungal antibiotic, exhibiting MICs in the range of 0.25 to 8 nanomolar . Tolytoxin also inhibits the growth of a variety of mammalian cells at similar doses, without specific inhibition of macromolecular synthesis . The effects in mammalian cells are primarily cytostatic, with cell death being time- and dose-dependent . Tolytoxin is highly toxic to mice, exhibiting an LD50 (ip) of 1.5 mg/kg . No antibacterial, antiviral, or hemolytic activities were observed.

Comp Biochem Physiol B, 1992 Jan-Feb, 101(1-2), 179 - 83
Oral immunization with Escherichia coli K-12 of the fifth instar larvae of the silkworm, Bombyx mori, reared on an artificial diet under completely aseptic conditions; Ichimori H et al.; 1 . Effect of oral administration of live or formalin-treated Escherichia coli (E . coli) K-12 to the fifth instar, days 1 and 3 larvae of the silkworm, Bombyx mori, on induction of antibacterial activity in the haemolymph was investigated using the silkworms reared on an artificial diet under completely aseptic conditions . 2 . When live E . coli was administered to the male day 1 larvae, low but significant antibacterial activity of 3.8 mm was detectable in the haemolymph of one individual at 48 hr after immunization . The proportion of the larvae to express antibacterial activity increased thereafter and at 120 hr after immunization, all three individuals showed antibacterial activity . In day 3 male larvae, activity was detectable at 48 and 72 hr after immunization . 3 . When formalin-treated E . coli was orally administered to days 1 and 3 male larvae, no activity was detectable at any time post-immunization . 4 . In the second experiment, when day 1 larvae, females and males were orally immunized with live E . coli, only females showed antibacterial activity in the haemolymph, beginning from 24 hr after immunization and up to 96 hr . 5 . Removal of an antibiotic, chloramphenicol, from ingredients of an artificial diet was required for induction of antibacterial activity with oral administration of live E . coli . 6 . When live E . coli that grows at pH 9.0 was selected and used for oral immunization, antibacterial activity was induced both in females and males at 72 hr after immunization and the activity was observed at 96 hr . 7 . These results suggest that establishment of oral immunization with live E . coli in the silkworm larvae requires multiplication of E . coli in the midgut lumen and possibly its colonization on the luminal surface.

Comp Biochem Physiol B, 1992 Jan-Feb, 101(1-2), 173 - 8
Induction of antibacterial activity in the haemolymph of the silkworm, Bombyx mori, by injection of formalin-treated Escherichia coli K-12 in the anterior and posterior body part of the ligated larvae; Sumida M et al.; 1 . Induction of antibacterial activity was investigated in the ligated fifth instar larvae of the silkworm, Bombyx mori, by injection of formalin-treated Escherichia coli K-12 into the haemocoel in the anterior and in the posterior body part, followed by activity determination by inhibition zone assay of the haemolymph at 12 and 24 hr after immunization . 2 . At 12 hr after immunization, high antibacterial activity, approximately 6.8-7.5 mm in the anterior body part and 4.5-6.4 mm in the posterior body part in diameter of a clear zone (2.0 mm for no activity) was detectable in day 3 larvae . This result was in good contrast to expression of lectin gene in the ligated flesh fly, Sarcophaga peregrena (Shiraishi and Natori, 1988, FEBS Lett . 232, 163-166), in which only the anterior part of insect responded to stimulus of injury . 3 . Antibacterial activity at 24 hr after immunization in days 3 or 4 ligated larvae was lower than that at 12 hr; 4.0-4.5 mm of activity was observed in the anterior body part, and no activity was observed in day 3 ligated larvae in the posterior body part . 4 . Acid polyacrylamide gel electrophoresis of the haemolymph of immunized insects followed by overlay assay showed that the size of antibacterial activity bands were similar between the haemolymph from 12 hr and from 24 hr, and between the anterior and the posterior body part . This result was contradictory to the observation of activity by inhibition zone assay . The activity bands were associated with peptides that were similar to cecropin-like peptides A and B in the silkworm.(ABSTRACT TRUNCATED AT 250 WORDS)

Comp Biochem Physiol B, 1992 Jan-Feb, 101(1-2), 165 - 71
Antibacterial activity inducible in the haemolymph of the silkworm, Bombyx mori, by injection of formalin-treated Escherichia coli K-12 during the fifth larval instar and pharate adult development; Sumida M et al.; 1 . Antibacterial activity inducible in the haemolymph of the silkworm, Bombyx mori, by immunization, i.e . by injection of formalin-treated Escherichia coli (E . coli) K-12 during the fifth larval instar and pharate adult development that was reared aseptically on an artificial diet was determined by inhibition zone assay using the same bacterium as a test organism . 2 . A peak of antibacterial activity was observed in each development stage; approximately 8 mm in diameter of a clear zone at days 3 or 4 in the fifth larval instar and approximately 5 mm at day 1 in the pharate adults . 3 . Acid polyacrylamide gel electrophoresis of immunized haemolymph followed by overlay assay showed that an activity band was associated with two peptide bands that were similar to the cecropin-like peptides A and B that were reported in the silkworm (Morishima et al., 1988, Agri . Biol . Chem . 52, 929-934) . Any other activity bands were not observed . No activity band was detectable from the haemolymph of non-immunized insects . 4 . Fractionation of antibacterial peptides in immunized haemolymph on a CM-cellulose column resulted in separation of two groups of activity, both in the fifth instar larvae and in the pharate adults with a slight difference in elution conditions . 5 . Duration of high antibacterial activity induced by a single immunization was approximately 12 hr in the fifth instar day 3 larvae and 48 hr in the day 2 pharate adults.

Folia Microbiol (Praha), 1992, 37(5), 386 - 8
Pesticidal activity of virginiamycins S1 and M1; Prikrylova V et al.; Virginiamycins S1 and M1, two major components of the antibacterial antibiotic complex produced by Streptomyces virginiae and used as an animal growth promoter in animal husbandry, exhibited a selective insecticidal activity against Leptinotarsa decemlineata comparable with the effect of the organophosphorus pesticide Metathion . An acaricidal effect of the two compounds on eggs of Tetranychus urticae was also observed.

Infection, 1992, 20 Suppl 3, S213 - 6; discussion S217-20, S224
Prophylaxis in urological surgery; Janknegt RA; Prophylaxis in urological surgery is usually taken to mean antibacterial agents . However, in this study, other factors such as the environment, patient risk and surgical risk factors are also taken into account . Because patients have a wide variety of possible risk factors, individual variations must be possible . In standard transurethral resection in non-risk patients, single-dose preoperative prophylaxis may be sufficient . In open surgery prophylactic measures should be varied according to the extent of the procedure.

Scand J Infect Dis Suppl, 1992, 83, 34 - 40
Macrolides and the immune system; McDonald PJ et al.; Macrolides achieve much greater in vivo and clinical efficacy than might be expected from standard in vitro testing . There is accumulating evidence to suggest that macrolides act synergistically with the host immune system . In contrast to beta-lactams, macrolides have increased activity in serum . Phagocytes are a key component of the host immune system against intracellular pathogens . Antibiotics can alter bacterial susceptibility to both uptake and intracellular phagocytic killing . Macrolides appear to enhance phagocyte killing of bacteria whereas beta-lactams have a limited or negative effect . Both macrolides and quinolones achieve high intraphagocytic concentrations that are associated with intracellular antibacterial activity . Azithromycin, which is chemically related to the macrolides, achieves particularly high intracellular levels within phagocytes which may be associated with enhanced synergistic activity.

Drugs Exp Clin Res, 1992, 18(6), 205 - 16
Low toxic derivatives of istamycin B: synthesis and preliminary evaluation; Ikeda D et al.; 3-O-Demethylistamycin B derived from istamycin B was one of the most potent aminoglycoside antibiotics against various bacteria . 3-O-Demethylistamycin B, however, showed considerable acute toxicity in mice . The authors attempted to prepare the derivatives of istamycin B having high potency and low toxicity . The selective N-acylation or N-amidination at the C-2 position of istamycin B could not improve the acute toxicity . The replacement of the amino group at the C-2 position of istamycin B by a hydroxyl group markedly decreased the acute toxicity . Among 2'-deamino-2'-hydroxyistamycins, 4-N-(beta-alanyl)-2'-deamino-3-O-demethyl-2'-hydroxyistamycin B0 (9d) showed good antibacterial activity against Gram-positive and Gram-negative bacteria and a low acute toxicity in mice.

Toxicol Pathol, 1992, 20(2), 246 - 52
Morphologic and biochemical changes in articular cartilages of immature beagle dogs dosed with difloxacin; Burkhardt JE et al.; Quinolones are efficacious antibacterial compounds, but they have been associated with arthralgia in human patients; experimentally, they have caused lesions in articular cartilages of immature animals . The earliest morphologic and biochemical changes induced in articular-epiphyseal cartilage complexes by difloxacin, a fluoroquinolone, were investigated in 27 3-month-old Beagle dogs that were dosed orally with the drug at 300 mg/kg body weight per day . Paraffin-embedded sections of humeral and femoral heads that were stained with either hematoxylin and eosin or toluidine blue and fast green were evaluated histologically, and lesions were scored according to established criteria . Although morphologic changes were not observed in cartilages of the control dogs or of the treated dogs in the 24-hr group, the severity of lesions, as represented by mean scores for lesions, increased during the 36-48 hr after dosing . The initial morphologic change, observed in cartilages from the treated dogs of the 36- and the 48-hr groups, was necrosis of chondrocytes that was rapidly followed by disruption of extracellular matrix and formation of fissures . Although glycosaminoglycan was aggregated along the margins of fissures, its concentration was not reduced in cartilages of any group of treated dogs . Collagen, however, was depleted from the cartilages of the dogs that were euthanized 36 or 48 hr after the first dose of difloxacin . Because degenerative changes were observed ultrastructurally in chondrocytes by 24 hr in a previous study, it was concluded that collagen was lost from affected cartilages as an early sequel to the degeneration of chondrocytes.

Pharm Acta Helv, 1992, 67(11), 301 - 7
Interaction of preservatives with macromolecules: Part I--Natural hydrocolloids; Kurup TR et al.; Antibacterial activity of methyl-p-hydroxybenzoate against Ps . aeruginosa was evaluated in the presence of varying concentrations of acacia, tragacanth, sodium alginate, guar gum and carrageenin . All these hydrocolloids reduced the antibacterial activity to varying degrees . Tragacanth and guar gum inhibited the activity to a greater extent than acacia, sodium alginate and carrageenin . Hydrocolloids reduce the antibacterial activity of preservatives in two ways . Interaction of the preservative with hydrophilic macromolecules and subsequent reduction in the availability of preservative appears to be the predominant mechanism by which tragacanth and guar gum reduce the activity of methyl-p-hydroxybenzoate . Acacia, sodium alginate and carrageenin apparently act by offering physical protection to microbial cells from the action of the preservative . It is also probable that these hydrocolloids provide more favourable media for microbial growth thereby increasing the preservative requirement for adequate preservation.

Probl Tuberk, 1992, (9-10), 25 - 8
{The use of intrapulmonary needle-jet injections of chemical preparations in the preoperative management of patients with pulmonary tuberculosis}; Cherkasov VA et al.; Among the various methods of antibacterial preparation injection for the management of pulmonary tuberculosis the intrapulmonary injection techniques with the help of a needle-stream injector (NSI-1) still remain little studied . The experience of using these techniques for treating more than 200 patients, among whom 23 patients were later operated on, showed that the early use of the method (immediately after the diagnosis was established) helped to stabilize the process in 1-1.5 months . This made it possible to perform operations within 3 months after the diagnosis was made . The method proved effective also in patients who did not present favourable dynamics during 3-6 months of the use of the traditional therapeutic methods . The results obtained allow for the use on a wide scale of needle-stream injections in the preoperative management of destructive tuberculosis patients.

Med Pr, 1992, 43(4), 303 - 8
{Immunological profile of workers occupationally exposed to chlorine}; Moszczynski P et al.; Immunological profile of 42 men working under exposure to chlorine for a period from 2 to 38 years was analysed . Toxicological analyses of air samples which were carried out for 20 years showed similar chlorine concentration ranging from 0.21 to 1.05 mg/m3 . The number of B, T, and non-B, non-T lymphocytes was determined as well as the C3c, C4 complement components and proteins of acute phase reaction: alpha 1-acid-glycoprotein, haptoglobin and ceruloplasmin in the serum . Chronic exposure to chlorine produced a stimulating effect on the immune system, which was manifested by elevated IgA, IgD and IgM levels, the concentration of acute phase reaction proteins and increased number of B lymphocytes . The observed phenomenon had no influence on the antibacterial and anticancer immunity of the workers.

Ann Dermatol Venereol, 1992, 119(6-7), 463 - 70
{Atypical cutaneous mycobacterium diseases . Results of a national survey}; Bonafe JL et al.; We report the results of a retrospective inquiry concerning atypical cutaneous mycobacterioses in France over the last 5 years . Ninety-two cases were observed, contracted from aquariums (50 p . 100), in swimming pools (4.4 p . 100) and as a result of mesotherapy (15.2 p . 100); 66.3 p . 100 of the patients had no other pathology; 17.4 p . 100 were immunodepressed . Bacteriological examination was positive in 44.7 p . 100 of the cases; swabbing, scratching and punturing were better than biopsy to obtain a bacteriological culture . Mycobacteria were identified in 59.8 p . 100 of the cultures . In order of frequency, the pathogens were Mycobacterium marinum (from aquariums), M . chelonae (from iatrogenic lesions) and M . avium-intracellulare (in immunodepression) . M . fortuitum, M . ulcerans, M . flavescens, M . haemophilum and M . kansasii were rare . The formation of epithelial giant-cell granulomas was observed in patients without any other pathology . Non-specific infiltration was found in patients with immunodepression and bacteriological examination was often positive in those with non-specific infiltrates . The treatment of atypical cutaneous mycobacterioses is always difficult; third generation tetracyclines and antibacterial combinations are often prescribed, but the results of in vitro tests are not reproducible in vivo . New antibiotics, such as clarithromycin, quinolones, ansamycin and clofazimine, are currently being tested.

Adv Pediatr, 1992, 39, 71 - 99
Intravenous immunoglobulin in the prevention and treatment of neonatal bacterial sepsis; Lassiter HA; IVIG has been shown in vitro to enhance many antibody-dependent immunologic functions . In animal models, IVIG enhanced the survival of septic neonates . In humans, preliminary data indicate that prophylactic IVIG may diminish the incidence of bacterial sepsis in VLBW neonates if sufficient doses of the immunoglobulin are administered repeatedly . IVIG administered after the onset of clinical symptoms may improve the survival of septic human neonates . However, the studies designed to assess the efficacy of IVIG to treat established sepsis have employed a small number of subjects and have, overall, provided inconclusive data . IVIG has been tolerated well by neonates, but the safety and long-term consequences of administering IVIG to newborn infants are not yet defined . IVIG will likely serve as a useful adjunct to enhance the antibacterial defenses of newborn infants . Use of IVIG in human neonates remains experimental at this time; therefore, the clinical application of IVIG for the prevention or treatment of neonatal bacterial sepsis should await the development of guidelines to be derived from ongoing multicentered, placebo-controlled clinical trials.

Respiration, 1992, 59 Suppl 3, 24 - 7
Adhesion molecules in antibacterial defenses: effects of bacterial extracts; Marchant A et al.; Adhesion of polymorphonuclear leukocytes (PMN) to vascular endothelium is one of the first events in their response against local bacterial infection . Different adhesion molecules sequentially mediate PMN adherence to endothelium and extravasation into inflamed tissues . We show that bacterial extracts OM-85 BV and OM-89 increase the expression of adhesion molecules at the surface of PMN and we suggest that this upregulation could be linked to the beneficial effect of bacterial extracts in the prevention of respiratory tract infections.

Caries Res, 1992, 26(4), 293 - 8
Effect of glutardialdehyde on secondary caries in situ; Dijkman GE et al.; In this paper the results are presented on the effect glutardialdehyde (GDA) on the in situ demineralization of human enamel and dentine around an artificial gap of 200 microns width . In this model secondary enamel and dentine caries is simulated in situ; the mineral loss was quantified . The results show that a 2-min application of a 2% acidic GDA solution reduces dentine demineralization substantially, but does not influence enamel demineralization . Microradiography showed a reduction of mineral loss values around the gap in dentine by about 30% . The beneficial effect of GDA on dentine is presumably a combined result of collagen fixation, the reduced diffusion of calcium and phosphate ions out of the dentine lesion, and antibacterial action . The results indicate that GDA might play a role in the future reduction or prevention of secondary dentine caries.

Scand J Gastroenterol Suppl, 1992, 191, 28 - 31
Triple therapy with sucralfate is as effective as triple therapy containing bismuth in eradicating Helicobacter pylori and reducing duodenal ulcer relapse rates; Louw JA et al.; Duodenal ulcer relapse rates after therapy with sucralfate or bismuth are lower than those after H2-receptor antagonist therapy . This may be mediated by an antibacterial effect of these drugs on Helicobacter pylori . Bismuth has become an integral part of 'triple therapy' because of its documented anti-H . pylori effect . In vitro and clinical data suggest that sucralfate may also have an anti-H . pylori effect . The aim of this randomized, prospective therapeutic trial was to compare the efficacy of triple therapy containing bismuth with that containing sucralfate and to determine the effect of therapy with these combinations on duodenal ulcer relapse . Forty H . pylori-positive duodenal ulcer patients were healed with omeprazole and randomized to receive either 1 g sucralfate four times daily or 120 mg bismuth compound four times daily . All patients received 400 mg metronidazole three times daily and either 250 or 500 mg tetracycline four times daily for 7-14 days . Thirty-five patients could be analysed . Overall eradication rates did not differ in the treatment groups (10 of 17 eradicated with sucralfate and 11 of 18 with bismuth) . Relapse rates were significantly lower in the eradicated group (1 of 21 compared with 8 of 14 in the non-eradicated group) and did not differ between treatment groups in those patients not eradicated . A triple therapy regimen utilizing sucralfate appears to be as effective as the bismuth-containing regimen.

Pharm Acta Helv, 1992, 67(7), 195 - 7
Synthesis and pharmacological activity of imidazo {2,1-b} thiazole nitriles, amides and p-sulfamidophenylhydrazones; Andreani A et al.; The synthesis of three series of new imidazo {2,1-b} thiazoles (nitriles 1-7, amides 8-14 and p-sulfamidophenylhydrazones 15-24) is reported . Among the compounds tested, only 12 showed a borderline diuretic activity . Compounds 15-24, possible prodrugs of sulfanilamide, were devoid of antibacterial activity.

Probl Tuberk, 1992, (5-6), 41 - 5
{Morphological characteristics of reparative processes in tuberculosis and the effect of pesticides}; Arifkhanova SI et al.; The paper deals with the results of a comparative morphologic, toxicologic and biochemical study of the character of reparative processes in destructive forms of pulmonary tuberculosis, specific features of non-coordination of collagen metabolism depending on the cumulation of organochlorine and organophosphorus pesticides and in the absence of their residual quantities in the patient's body on admission to a hospital and during current antibacterial therapy . The resected and removed lungs and blood of 1063 patients were used for the study . Specific features of a tuberculosis course, the duration and effectiveness of antibacterial therapy, the character of reparative processes, characteristic features of collagen metabolism and collagenosis, the character and dissemination of residual changes due to therapy were established in the compared groups of patients.

Pediatriia, 1992, (4-6), 43 - 7
{Tactics in using antibiotics in diffuse forms of chronic nonspecific pneumonia in children}; Klimanskaia EV et al.; The authors provide the results obtained during many years of studying different aspects of antibacterial treatment of purulent endobronchitis in children with prevalent forms of chronic pneumonia . The study was attempted at the clinic for disease of childhood, I.M . Sechenov Moscow Medical Academy . Base the complex program of such treatment, which rests on etiotropic , correspondence of the antibiotic administration to the activity of the infectious inflammatory process in the bronchi, and immunomodulating therapy carried out according to indications if any . Introduction of the antibiotic therapy program into clinical practice allowed the attainment of good direct results in 87.6% of patients and of stabilization of endobronchitis in 47% of patients within 1.5 to 3 years.

Med Microbiol Immunol (Berl), 1992, 181(2), 87 - 98
Antibacterial effect of bovine milk antibody against Escherichia coli in a mouse indigenous infection model; Nomoto K et al.; A skim-milk fraction and a whey-protein concentrate (WPC) fraction were prepared from the cows that had been immunized with E . coli isolated from the mouse intestine . The antibacterial effect of these fractions against E . coli was examined . They contained antibody with a high affinity for E . coli strain 48, a representative strain in the mouse intestine, which is composed of a large amount of IgG and smaller amounts of IgA and IgM . Although these fractions showed no bactericidal or bacteriostatic activity against E . coli 48 directly in vitro, they exhibited strong agglutination and opsonization activities against the bacteria in vitro . The bacteria opsonized with the WPC fraction were taken up more effectively by liver macrophages in vivo, compared with unopsonized E . coli, after an intravenous injection into mice . Oral administration of the skim-milk fraction to mice significantly reduced the susceptibility to the lethal toxicity of 5-fluorouracil (5 FU) . The increase in the population levels of E . coli in the intestinal tract after administration of 5 FU was inhibited by oral administration of the skim-milk fraction . These results strongly suggest that specific antibody may be effective in the prophylaxis against the indigenous infection with gram-negative bacteria such as E . coli after a period of chemotherapy in cancer patients.

Digestion, 1992, 51 Suppl 1, 11 - 6
Helicobacter pylori, peptic ulcer disease and inhibition of gastric acid secretion; Rune S; Recent studies have been reviewed to establish the possible importance of the interaction between Helicobacter pylori infection and gastric acid secretion . H . pylori infection results in increased gastrin release, but this does not lead to gastric acid hypersecretion and gastrin normalizes after eradication of the infection . An optimal, well-tolerated treatment strategy against H . pylori infection has not yet been clearly defined . One potentially useful approach may be to improve the antibacterial efficacy of antibiotics by effectively regulating gastric acidity . H2-receptor antagonists have no effect against H . pylori infection, while omeprazole (an acid pump inhibitor) appears to have a bacteriostatic action . Combination therapy with omeprazole and amoxycillin has been found to eradicate H . pylori in 50-80% of patients with duodenal ulcer, leading to a significant reduction in ulcer recurrence.

Crit Rev Oral Biol Med, 1992, 3(4), 307 - 32
Cystatins--inhibitors of cysteine proteinases; Bobek LA et al.; The cystatin superfamily of proteins, derived from a common ancestor, is comprised of a diverse group of potent cysteine proteinase inhibitors and antibacterial/viral agents grouped into several families . This review concentrates on family 2 cystatins, namely, the human salivary cystatins and cystatin C . Emphasis is given to their physicochemical and functional properties at both the protein and the molecular level . The role of cystatins in disease processes, including those in the oral cavity, is also discussed . Finally, future directions for cystatin research in oral biology are presented.

Ann Trop Paediatr, 1992, 12(1), 105 - 9
Management of accidental kerosene ingestion; Singh H et al.; Accidental kerosene ingestion is still a common problem in Libya . It causes considerable morbidity and occasionally mortality . The role and choice of antibacterial agents in its management remain unsettled . Pulmonary damage has been reported as resulting from aspiration . In aspiration pneumonia, anaerobic organisms may be important pathogens and metronidazole may have a place in therapy . The present randomized trial in 100 children with accidental kerosene ingestion assesses the role of ampicillin, carbenicillin and metronidazole in its management . The results are not conclusive but chemoprophylaxis appears to decrease morbidity . Of the various regimens used, the ampicillin/metronidazole combination was found to be slightly better than the others . Further study is recommended.

J Antibiot (Tokyo), 1992 Jan, 45(1), 20 - 8
Protactin, a new antibiotic metabolite and a possible precursor of the actinomycins; Hanada M et al.; Streptomyces cucumerosporus strain L703-4 (ATCC 53784) produces a new 4-methyl-3-hydroxyanthraniloylpentapeptide lactone for which we have proposed the name protactin, in addition to several actinomycin components . Protactin is rather resistant to air oxidation but it can be converted to a new actinomycin, actinomycin Zp by ferricyanide oxidation . Actinomycin Zp possesses in vitro antibacterial activity and in vivo antitumor activity against P-388 leukemia in mice.

J Chem Technol Biotechnol, 1992, 53(3), 227 - 36
Synthesis and application of novel sulpha drugs based on quinoxaline-2-one and/or quinoxaline-2-thione; Awad IM; Some novel azo-Sulpha drugs as 3-methyl-N-azo-(4'-substituted heterocyclo-benzene-sulphamoyl) quinoxaline-2-ones (1-11) and 3-methyl-N-azo-(4'-substituted heterocyclo-benzene-sulphamoyl)-quinoxaline-2-thiones (1'-11') were synthesized by coupling 4'-substituted heterocyclo-benzene-sulphamoyl diazonium acetates with 3-methyl-N-(1H)-quinoxaline-2-one and/or with 3-methyl-N(1H) quinoxaline-2-thione in acid medium . The corresponding iron (III) (1a-11, 1'a-11'a) copper (II) (1b-1b'-7b') and mercury (II) (1c-11c, 1c'-11c) chelates were also prepared in a 1:1 metal-to-ligand ratio . The ligands and their chelates were characterized on the basis of microanalysis, UV, IR and H'-NMR spectrometry, and were tested in vitro for their antibacterial and antifungal activities.

Rev Chil Obstet Ginecol, 1992, 57(4), 273 - 8
{Sexually transmitted microorganisms and immunoglobulins in the amniotic fluid in mothers who carry sexually transmitted diseases}; Bernal JN et al.; Fetal behaviour as an intrauterine patient is unknown . In the diagnosis of sexually transmitted diseases (STD) and in the criteria for treatment only the mother is considered leaving the fetus out . The presence of immunoglobulin M in the amniotic fluid is an indicator of fetal infection and could allow an accurate diagnosis of fetal disease or treatment, if the measurement is related to the presence or absence of organism in the amniotic fluid . In this way, the study of fetal behaviour under these conditions could be done . The objective of this research was to determine the presence of STD organism in the amniotic fluid of the STD infected pregnant women and to evaluate the prevalence and evolution of these pathologies in the fetus . No STD organism, nor immunoglobulin M were found in the 13 samples of amniotic fluid (8 pre and 5 post-treatment) of infected pregnant women . The presence of microorganisms and its relation to immunoglobulin M was not observed . More cases are needed to arrive to a conclusion regarding fetal immunology and to a better understanding of antibacterial properties of the amniotic fluid . We concluded that no contamination in the amniotic fluid or fetal infection was found in pregnant women with STD.

Vestn Khir Im I I Grek, 1992 Jan, 148(1), 28 - 32
{Antibacterial and detoxification therapy in acute appendicitis}; Chalenko VV et al.; An analysis of clinical effectiveness of antibacterial therapy, photomodification of autoblood, hemosorption and their combinations was made in 395 patients with acute appendicitis . It was established that no antibacterial and desintoxicating therapy is required in catarrhal appendicitis . The prophylactic application of photomodification of autoblood is thought to be most expedient for phlegmonous appendicitis at the postoperative period, a combination of antibacterial therapy and photomodified autoblood--for gangrenous appendicitis, a combination of antibacterial therapy, photomodification of autoblood and hemosorption--for appendicular diffuse suppurative peritonitis.

Free Radic Res Commun, 1992, 17(6), 387 - 98
Possible reasons for differences in phototoxic potential of a 5 quinolone antibacterial agents: generation of toxic oxygen; Wagai N et al.; The reason for the differences in phototoxic potential between the 5 quinolone antibacterial agents lomefloxacin, enoxacin, ciprofloxacin, ofloxacin and DR-3355 (the s-isomer of ofloxacin) in mice was investigated . Superoxide anion, hydrogen peroxide (H2O2), and bleaching of p-nitrosodimethylaniline (B-NDMA) were detected in quinolone solutions during irradiation with ultraviolet-A (UVA) . Apparent levels of H2O2 and the B-NDMA per mole of quinolone paralled the phototoxic potentials in the mice . The N-NDMA induced by quinolones and UVA was inhibited partially by treatment with D-mannitol and dimethylsulfoxide, and also with diethylenetriamine-pentaaceticacid (DTPA), suggesting that Haber-Weiss and Fenton reactions occurred . UVA concentration-dependently increased the level of the B-NMDA in H2O2 solution and the swelling in the ear pretreated by intra-auricular injection of H2O2 . Both augmentations were inhibited by DTPA or DMSO . The swelling induced by the 5 quinolones and UVA was completely inhibited by pretreatment with dimethylsulfoxide . Oxygen consumption was detectable during the photodegradation, and increased with time . These results showed that the phototoxic potentials of the 5 quinolones were probably related to the amounts of toxic oxygens generated in the target cells during irradiation.

Arch Toxicol, 1992, 66(6), 392 - 7
Possible direct role of reactive oxygens in the cause of cutaneous phototoxicity induced by five quinolones in mice; Wagai N et al.; The mechanisms of phototoxicity induced in mice by five quinolone antibacterial agents were investigated using mouse 3T3 fibroblast cells and Balb/c mice . In the in vitro study, the cultured cells were exposed to ultraviolet-A (UVA) in the presence of the five quinolones lomefloxacin, enoxacin, ciprofloxacin, ofloxacin and DR-3355 (the s-isomer of ofloxacin) . Cytotoxicity after irradiation was assayed by the neutral red and MTT assay methods, both of which revealed dose-dependent phototoxicity for all five quinolones . Phototoxicity was inhibited by the addition of catalase, and was augmented by the addition of superoxide dismutase . Dimethylthiourea (a hydroxyl radical scavenger) protected against phototoxicity induced by four quinolones, but not against that by enoxacin . These results indicated that superoxide anions, hydrogen peroxide and hydroxyl radicals were generated in solutions of these quinolones under UVA irradiation . In the in vivo study, mice were injected in the auricle with hydrogen peroxide . Ear swelling reactions appeared dose dependently . When irradiated, these reactions were significantly augmented . These data suggested that cutaneous phototoxicity in Balb/c mice is initiated by the generation of reactive oxygens in the target tissue, especially of hydroxyl radicals.

Clin Pharmacokinet, 1992, 22 Suppl 1, 90 - 7
Effects of temafloxacin and ciprofloxacin on the pharmacokinetics of caffeine; Mahr G et al.; A number of quinolone antibacterial agents, particularly enoxacin, pefloxacin, pipemidic acid and ciprofloxacin, are known to decrease the clearance of methylxanthines . The effects of temafloxacin and ciprofloxacin on the pharmacokinetics of caffeine were therefore compared in a 3-way crossover study in 12 healthy young volunteers . Each volunteer received 183mg once-daily doses of caffeine in conjunction with twice-daily placebo, temafloxacin 600mg and ciprofloxacin 750mg in 3 separate phases according to a randomised sequence . A doubling of the area under the plasma concentration-time curve (77.8 vs 31.8 mg/L.h) and terminal-phase half-life (9.7 vs 4.5h) of caffeine were observed in the presence of ciprofloxacin . The magnitude of the reduction in the intrinsic clearance of caffeine produced by ciprofloxacin was greater than that described in the literature for ciprofloxacin and theophylline . This may partly be explained by intertrial differences in dosage and study design . Coadministration of temafloxacin did not have any effect on the pharmacokinetics of caffeine, confirming results of other studies suggesting that this agent does not affect methylxanthine clearance . Accordingly, it appears that restriction of caffeine intake during temafloxacin therapy is not necessary.

Clin Pharmacokinet, 1992, 22 Suppl 1, 48 - 56
The effect of food on the bioavailability of temafloxacin . A review of 3 studies; Granneman GR et al.; Temafloxacin is a new fluoroquinolone antibacterial agent . Previous pharmacokinetic studies have shown that the extent of absorption of temafloxacin is independent of dose and that the dispositional pharmacokinetics are linear . The pharmacokinetics of 3 tablet formulations of temafloxacin were investigated in phase I studies in healthy adult volunteers, to determine whether the bioavailability is altered by the presence of food . Results of these studies indicate that the absorption of temafloxacin is slightly enhanced by concomitant administration of food . Thus, special coordination of temafloxacin administration and meals appears to be unnecessary.

Contact Dermatitis, 1992 Jan, 26(1), 5 - 10
Scarified photopatch testing in lomefloxacin photosensitivity; Kurumaji Y et al.; We report the results of scarified photopatch testing in 3 patients with photosensitivity to lomefloxacin, a new quinolone antibacterial agent introduced onto the Japanese market in April 1990 . The patients developed pruritic eczematous lesions on sun-exposed areas 5 days to 3 weeks after they had started taking lomefloxacin . 2 cases reacted positively to lomefloxacin on scarified photopatch testing down to 0.1% pet., and 1 patient down to 10% pet . One of them also showed positive reactions on conventional photopatch testing . Scarified photopatch testing with 7 other pyridone carbonate derivatives in 2 of the 3 cases, however, did not show any positive reactions . Patch and scarified patch testing were negative in all patients . The clinical course, clinical and histological findings and results of skin tests in these patients suggest that photoallergic mechanisms are involved . This is the 1st report of positive reactions on scarified photopatch testing, which appears to be a useful method of detecting the causative drug in drug-induced photosensitivity.

Antimicrob Agents Chemother, 1992 Jan, 36(1), 81 - 6
Induction of calf thymus topoisomerase II-mediated DNA breakage by the antibacterial isothiazoloquinolones A-65281 and A-65282; Kohlbrenner WE et al.; A number of quinolones and related antibacterial compounds were screened for activity against calf thymus topoisomerase II by using the P4 unknotting and DNA breakage assays . Several compounds from different structural classes which inhibited DNA unknotting with 50% inhibitory concentrations ranging from 8 to 25 micrograms/ml were identified . Two experimental isothiazoloquinolones from this group, designated A-65281 and A-65282, were also found to induce considerable DNA breakage mediated by calf thymus topoisomerase II, with 32P-end-labeled pBR322 as the substrate . These compounds were nearly as potent as teniposide, with DNA breakage activity evident at concentrations as low as 4 micrograms/ml . However, some differences in DNA cleavage patterns from those with teniposide were evident . These studies have thus identified a new class of agents which have activity against both bacterial and eukaryotic type II topoisomerases . The implications of these data for the selectivity of topoisomerase-directed compounds and the potential toxicity of such compounds developed as antibacterial agents are discussed.

J Med Chem, 1992 Jan, 35(1), 94 - 9
Synthesis and antibacterial activity of new tetracyclic quinolone antibacterials; Taguchi M et al.; A series of 8-substituted-9,1-(epoxymethano)-7-fluoro-5-oxo-5H- thiazolo{3,2-a}quinoline-4-carboxylic acids having a novel tetracyclic structure was synthesized and tested for antibacterial activity . The nature of the heteroatom (N, O, or S) substituted at the 8-position had little influence on the antibacterial activity . Among the six pyrrolidinyl derivatives and the five piperazinyl derivatives, the 8-(3-hydroxy-1-pyrrolidinyl) derivative 6h and the hydrochloride of the 8-(4-methyl-1-piperazinyl) derivative 6l showed the most potent activity against both Gram-positive and Gram-negative bacteria . Against nalidixic acid resistant strains, isolated from Escherichia coli KC-14, compound 6h was less potent than 6l . Replacement of the piperazinyl nitrogen atom by a carbon atom, an oxygen atom, or a sulfur atom (corresponding to the piperidino, morpholino, or thiomorpholino group, respectively) enhanced the activity against Gram-positive bacteria, but reduced the activity against Gram-negative bacteria . Compound 6l also showed potent in vivo antibacterial activity against Gram-positive and Gram-negative bacteria, and did not cause convulsions in mice with the concomitant administration of fenbufen . Replacement of the carboxy group by a sulfonic acid group in 6l resulted in a complete loss of antibacterial activity.

Rev Belge Med Dent, 1992, 47(4), 86 - 100
{Medications for endodontic use}; Lardinois ML; Medication can never disinfect a badly shaped canal and successful treatment will depend on the endocanal preparation . Despite the indisputable antibacterial efficacy of Rockles 4 in vitro, use of this medicament should be banned because of its toxicity, its mutagenic and antigenic action and its long-term inefficacy in vivo . The same goes for all other antiseptics, anti-inflammatory agents and antibiotics mentioned, that should be discarded because of their harmful effects on patients or their inefficacy on endodontic flora . Our endodontic medicine cabinet should only contain the following products: irrigation agent: NaOCl 2.5% medication in 2 sessions: calcium hydroxide prescription or 'Reogan rapide'.

Polim Med, 1992, 22(4), 17 - 29
{Effect of different vascular prosthesis materials on blood platelets, blood clotting and fibrinolysis}; Glowinski S et al.; Studies were performed on Dacron vascular prostheses (USA), Gore-Tex (Germany), polyester prostheses (Czechoslovakia), Lawsan (Russia), as well as on DALLON-standard and DALLON-double velour prostheses (Poland), non-impregnated or impregnated with collagen, with heparin and albumin, with antithrombotic and antibacterial preparation, and with antibacterial preparation . In vitro, all the materials of vascular prostheses cause an adhesion of platelets in different degree, increase the availability of platelet factor 3, release platelet factor 4, reduce the blood clot retraction, shorten clotting time of the whole blood as well as recalcination time of intact plasma and increase the prothrombin consumption . None of the materials induced platelet aggregation nor influenced the activity of fibrinolytic system . Prostheses impregnated with collagen or with heparin and albumin were the most thrombogenic . Those impregnated with antibacterial preparation or with antibacterial and antithrombotic preparations, and Gore-Tex prostheses showed the lowest thrombogenicity . Thrombogenicity of vascular prostheses not only depends on chemical structure of the material, but on the method of fibre manufacturing by individual producers as well.

Ciba Found Symp, 1992, 171, 45 - 59; discussion 59-63
Why are secondary metabolites biosynthesized? Sophistication in the inhibition of cell wall biosynthesis by vancomycin group antibiotics; Williams DH et al.; The evidence that secondary metabolites serve sophisticated roles in the survival strategy of the producer is briefly reviewed . This evidence stems from the common involvement of tens of kilobases of DNA in the programming of their synthesis, of up to several tens of discrete enzymic conversions in their biosynthesis, and of the existence of sophisticated mechanisms in the producers for resistance against their physiological effects . It also stems from a study of the molecular basis for these physiological effects . The molecular basis for the antibacterial action of the vancomycin group antibiotics is presented, and demonstrates that essentially every portion of these molecules appears to be finely honed to promote efficient antibacterial action.

Toxicol Pathol, 1992, 20(3 Pt 1), 436 - 49; discussion 449-50
Quinolone arthropathy--acute toxicity to immature articular cartilage; Gough AW et al.; A class effect of quinolone antibacterial agents observed during animal toxicity testing is a specific arthropathy (QAP) . Despite the growing list of laboratory animals susceptible to QAP and reports of arthralgia in patients treated with quinolones, the potential for QAP development in humans remains unknown . This review discusses current concepts in the biology of articular cartilage and how these concepts elucidate QAP pathogenesis . Biomechanical forces within synovial joints and toxicokinetic properties of quinolones contribute to QAP induction . Since a limited number of mechanistic pathways exist for acute articular damage, QAP may serve as a research tool to probe the pathobiology of injury to articular cartilage.

Yao Xue Xue Bao, 1992, 27(10), 738 - 42
{Synthesis and bacteriostatic activity of new thiosemicarbazone derivatives--amino mercaptotriazole Schiff bases}; Hou N et al.; 4-amino-3-(furan-2)-5-mercapto-1,2,4-triazole (Ia) and its ten Schiff bases derived from Ia with different aldehydes were synthesized . All the compounds were screened for activity against seven bacteria and three fungi . Most compounds were found to possess different inhibition effect on some bacteria and fungi . The azomethine group of Schiff bases is the active functional group and the substituted groups on the phenyl ring had definite effect on the bacteriostatic and fungistatic activities . 4-(5-Nitrofurfurylideneamino)-3-(furan-2)-5-mercapto-1,2,4-tria zol e (Ik) showed the most powerful antibacterial activity and broad antibacterial spectrum, while 4-salicylideneamino-3-(furan-2)-5-mercapto-1,2,4-triazole possessed strong activity against fungi.

J Hyg Epidemiol Microbiol Immunol, 1992, 36(3), 303 - 9
Antibacterial properties of the Vietnamese cajeput oil and ocimum oil in combination with antibacterial agents; Jedlickova Z et al.; Main antibacterially active agents obtained from plants-Cajeput essential oil--1,8 cineol, linalool, alpha-terpineol and terpinen-4-ol, for example from Melalleuce leucadendron (Myrtaceae) as well as essential oil from Ocimum gratissimum (Labiatae) were combined in tests in vitro with selected antibiotics . Above mentioned plant products were found to be effective medicaments for local application in modern medical practice . Combinations with antibiotics potentiated their therapeutical action . On the basis of tests in vitro the synergistic action of these two kinds of medicaments, i.e., preparations traditionally used for a few last decades--antibiotics--might be well applied for therapeutical needs.

Akush Ginekol (Mosk), 1992, (8-12), 27 - 30
{New aspects of the surgical procedure in abdominal delivery}; Mareeva LS et al.; A single-row suturing of the incision on the uterus after cesarean section with separate muscular-muscular sutures by synthetic dissolving threads holds good promise . Such suturing helped optimize the reparative processes in the uterine cicatrix and reduce the incidence of postoperative pyoseptic complications . Kaproag, an antibacterial suture material made in this country, proved to be the best for the purpose.

Pneumonol Alergol Pol, 1992, 60(1-2), 28 - 35
{Effect of TFX (Polfa) on the course of experimental bacterial infections in mice treated with ciprofloxacin, amikacin and cefoperazone}; Ciebieda I et al.; The effect of TFX-Polfa administered alone or with three antibiotics on the survival time in mice infected with E.coli and S.aureus was estimated . TFX has been administered 48, 24, 2 hours before and 24, 48 and 72 hours after infection, in doses of 10 mg/kg of body weight . Ciprobay has been administered 2 hours after infection, and every 24 hours during the experiment in dose of 15, 7.5 and 3.75 mg/kg of body weight . Amikin has been used in doses of 7.5, 3.75 and 1.87 mg/kg of body weight, Cefobid in doses of 30, 15 and 7.5 mg/kg of body weight . The antibiotics have been administered 2 hours after infection and every 12 hours to the end of experiment . Animals have been observed 10 days after infection . The positive effect of TFX on the survival time in mice infected with E.coli has been observed, but this preparation has given a little effect on the tested parameter in mice infected with S.aureus . Best antibacterial effect of Ciprobay and Amikin has been observed after administration of clinical doses . However, simultaneous therapy with TFX and tested antibiotics resulted in various (positive and negative) effects on the survival time during 10 days of observation.

Implant Dent, 1992 Spring, 1(1), 59 - 65
Antibacterial activity of dental implant metals; Berry CW et al.; This study was conducted to investigate the specific in vitro antibacterial effect of seven dental implant metals on oral bacteria which have often been identified in failing implants . The metals chosen for evaluation were titanium, chromium, cobalt, aluminum, iron, gold, and vanadium . These metals were selected because they are contained in many commonly used dental implants . The bacteria selected for this study included isolates of Porphyromonas endodontalis, Porphyromonas gingivalis, Prevotella intermedia, Prevotella melaniogenica, Actinobacillus actinomycetemcomitans, Actinomyces naeslundii, and Actinomyces viscosus . Sets of tubes containing either supplemented trypticase soy broth, brain-heart infusion-yeast extract, or brain-heart infusion-yeast extract with 5 percent defibrinated rabbit blood were aseptically prepared with doubling dilutions of the seven metals starting at an initial concentration of 500 micrograms/ml and terminating at 0 microgram/ml . Cultures of each organism were inoculated into each set of broth tubes containing all concentrations of metals . Tubes were incubated either anaerobically or in an atmosphere of 5 percent carbon dioxide for 48 hours at 35 degrees C and then assayed for ATP content which was proportional to the viable cellular biomass . The results showed that, although being bacteria and concentration dependent, all seven metals suppressed the growth of each organism . The rank order of antibacterial activity expressed by dental implant metals was gold > titanium > cobalt > vanadium > aluminum > chromium > iron.

Klin Khir, 1992, (8), 53 - 6
{Loop colostomy in patients with cancer of the colon and rectum}; Nazarov LU et al.; At the clinic of Scientific Research Institute of Proctology, Ministry of Public Health of Armenia, in 97 patients with complicated cancer of the colon and rectum, a two-barrel loop colostomy was created for the recent 10 years . Use of intraperitoneal method contributed to 3-fold decrease in incidence of postoperative purulent complications . Irrigation of a tumour site with antibacterial preparations in perifocal inflammation of colonic cancer together with carrying out the complex antibacterial therapy permits to perform the radical operations.

Optom Clin, 1992, 2(4), 59 - 72
New antibacterial drugs for topical ophthalmic use; Yolton DP; Three new antibacterial drugs have recently been approved for topical ophthalmic use . Ciprofloxacin (Ciloxan) and norfloxacin (Chibroxin) are fluoroquinolones with very broad activity spectra; both have been found to be safe and effective for the treatment of conjunctivitis . Ciprofloxacin, in the commercially available concentration (0.3%), has also been found to be a safe and effective treatment for corneal ulcers . Trimethoprim-polymyxin B (Polytrim) is a new combination product that has been used successfully for the treatment of conjunctivitis . Use of these three new drugs will significantly enhance the ability of the primary care clinician to treat bacterial infections of the cornea and conjunctiva.

Optom Clin, 1992, 2(4), 45 - 57
A review of common ophthalmic antibacterial and corticosteroid-antibacterial combination drugs; Thomas RK et al.; The use of antibacterial agents and corticosteroid-antibacterial combinations are essential to the practice of primary care optometry . In this paper we review common antibacterial drugs available for the treatment of ocular infection or prophylaxis, and offer some clinical guidelines for their use . Corticosteroid-antibacterial combination drugs, used primarily to suppress ocular inflammation, are also discussed, and the distinctions between common drugs are described.

J Enzyme Inhib, 1992, 6(2), 157 - 64
5838-DNI, a deoxyribonuclease inhibitor produced by Streptomyces sp . strain no . A-5838; Uyeda M et al.; 5838-DNI, an inhibitor of deoxyribonuclease (DNase) II from porcine spleen was produced by Streptomyces sp . strain No . A-5838 . The structure of 5838-DNI was shown to be 1,4,4a,5,12,12a-hexahydro-4,4a,11,12a-tetrahydroxy-3,8-dimethoxy-9- methoxycarbonyl-10-methyl-1,5,12-trioxo naphthacene . Although similar in structure to tetracenomycin C, which is an antibiotic against Gram-positive bacteria, 5838-DNI has different antibacterial activity . 5838-DNI was distinguished from 5923-DNI, a previously reported DNase II inhibitor, in inhibitory activity against each enzyme . 5838-DNI showed dependency of inhibition on pH and temperature, and inhibited phosphodiesterase I in a competitive manner . These data suggest that 5838-DNI is the first reported example of an inhibitor of microbial origin which is able to inhibit DNase II and phosphodiesterase I.

Am J Med, 1991 Dec 30, 91(6A), 51S - 66S
Comparative pharmacokinetics of ciprofloxacin and temafloxacin in humans: a review; Sorgel F et al.; Temafloxacin is a new antibacterial agent of the fluoroquinolone group . In comparison with ciprofloxacin, the current leading quinolone, temafloxacin shows higher and longer lasting plasma concentrations after equivalent doses due to an almost complete gastrointestinal absorption and a lower total clearance . Temafloxacin absorption is little influenced by food intake . Concomitant administration of antacids should be avoided; a time interval of at least 2 hours should elapse between intake of either quinolone and an antacid . Both quinolones are excreted mainly by the kidney . They differ in tubular secretion, which is high for ciprofloxacin and low for temafloxacin . The overall nonrenal elimination is similar for both compounds . Ciprofloxacin has a slightly higher extent of metabolism, while temafloxacin probably has a higher transintestinal elimination . The biliary excretion of both compounds is in the same range . The longer half-life of temafloxacin enables a once-daily dose regimen, whereas the usual recommended dosage of ciprofloxacin is twice daily . For both quinolones the apparent volumes of distribution per body weight are significantly above unity, indicating good tissue penetration with intracellular uptake . The concentrations in the extracellular fluids are directly related to the corresponding plasma concentrations . The penetration of temafloxacin into the body fluids investigated--tears, nasal secretion, saliva, sweat, prostatic and seminal fluid--in general exceeds that of ciprofloxacin (with the exception of seminal fluid) . Unlike ciprofloxacin, there is no drug interaction with methylxanthines . Comparative clinical studies reflecting the complex interrelating factors of host and pathogens are needed to demonstrate the significance of the pharmacokinetic differences between temafloxacin and ciprofloxacin.

J Biol Chem, 1991 Dec 25, 266(36), 24520 - 5
Insect immunity . Isolation from a coleopteran insect of a novel inducible antibacterial peptide and of new members of the insect defensin family; Bulet P et al.; Injection of heat-killed bacteria into larvae of the large tenebrionid beetle Zophobas atratus (Insecta, Endopterygota, Coleoptera) results in the appearance in the hemolymph of a potent antibacterial activity as evidenced by a plate growth inhibition assay . We have isolated three peptides (A-C) from this immune hemolymph which probably account for most of this activity . Their primary structures were established by a combination of peptide sequencing and molecular mass determination by mass spectrometry . Peptide A, which is bactericidal against Gram-negative cells, is a 74-residue glycine-rich molecule with no sequence homology to known peptides . We propose the name coleoptericin for this novel inducible antibacterial peptide . Peptides B and C are isoforms of a 43-residue peptide which contains 6 cysteines and shows significant sequence homology to insect defensins, initially reported from dipteran insects . This peptide is active against Gram-positive bacteria . The results are discussed in connection with recent studies on inducible antibacterial peptides present in the three other major orders of the endopterygote clade of insects: the Lepidoptera, Diptera, and Hymenoptera.

Science, 1991 Dec 6, 254(5037), 1521 - 3
Refined structure of charybdotoxin: common motifs in scorpion toxins and insect defensins; Bontems F et al.; Conflicting three-dimensional structures of charybdotoxin (Chtx), a blocker of K+ channels, have been previously reported . A high-resolution model depicting the tertiary structure of Chtx has been obtained by DIANA and X-PLOR calculations from new proton nuclear magnetic resonance (NMR) data . The protein possesses a small triple-stranded antiparallel beta sheet linked to a short helix by two disulfides and to an extended fragment by one disulfide, respectively . This motif also exists in all known structures of scorpion toxins, irrespective of their size, sequence, and function . Strikingly, antibacterial insect defensins also adopt this folding pattern.

Gastroenterology, 1991 Dec, 101(6), 1488 - 96
Gastrointestinal motor effects of erythromycin in humans; Sarna SK et al.; The effects of an antibacterially effective IV dose of erythromycin on gastrointestinal motor activity were investigated in eight normal healthy human volunteers in the fasted state and the fed state . Motor activity was recorded by a multilumen manometric tube . Data were analyzed visually and by a computer method . Blood samples were obtained for erythromycin and motilin assays . In the gastric antrum, erythromycin significantly increased the total duration, amplitude, and area under contractions from 0 to 60 minutes and frequency of contractions from 0 to 30 minutes from the start of its infusion in the fasted state . A similar response in the fed state occurred mostly from 0 to 30 minutes after the start of erythromycin infusion . By contrast, erythromycin inhibited the frequency and decreased the duration of small intestinal contractions in the fed state but had no effect in the fasted state . The gastric motor response was related to the plasma concentration of erythromycin, but not to plasma motilin . Erythromycin significantly shortened the duration of migrating motor complex disruption by a meal . Erythromycin also induced symptoms of upper abdominal pain, bloating, and nausea . Abdominal pain was related to strong antral contractions in both fasted and fed states; bloating occurred only in the fed state . Nausea occurred in both fasted and fed states, but it was not related to any specific pattern of motor activity . It is concluded that the strong antral contractions induced by erythromycin may accelerate the rate of gastric emptying, but they may also be responsible for causing the sensations of upper abdominal pain and bloating . The motor response to erythromycin is less during the fed than during the fasted state . The strong antral contractions induced by erythromycin are not mediated by the release of motilin.

Clin Exp Immunol, 1991 Dec, 86(3), 525 - 31
Ciprofloxacin enhances T cell function by modulating interleukin activities; Stunkel KG et al.; Ciprofloxacin (CIP) is a quinolone carboxylic acid derivative with a broad spectrum of antibacterial activity . CIP (0.1-30 micrograms/ml) enhanced DNA synthesis of mouse spleen cells and human peripheral blood lymphocytes (PBL) that had been activated with T cell mitogens or with alloantigens . In addition, CIP increased the amount of IL-2 found in the supernatants of phytohaemagglutinin (PHA)-stimulated human PBL . The presence of CIP in the medium (0.3-10 micrograms/ml) increased the levels of IL-1 found in the culture supernatants of adherence-enriched mouse macrophages, human monocyte/macrophages and a human monocytic cell line stimulated with lipopolysaccharide . In contrast there was no effect of CIP on the release of IL-1 by freshly isolated human monocytes or by cells of the keratinocyte line, A431 . CIP alone had no influence on the basal release of IL-2 by NOB-1 cells, a T cell line that responds to IL-1 with an increase in IL-2 synthesis, but, in combination with recombinant IL-1, CIP significantly enhanced the release of IL-2 by these cells . The results of this study suggest that CIP modulates the immune response at two levels--the production of IL-2 by activated T cells and the production of IL-1 by activated monocyte/macrophages . However, CIP did not affect the primary antibody response in vitro or in vivo against sheep erythrocytes and ovalbumin respectively . Thus the enhancing action of ciprofloxacin on the immune system appears to be restricted to T cell function and macrophage/T cell interactions.

FEMS Microbiol Lett, 1991 Dec 1, 68(3), 255 - 7
Enhanced clearing of Helicobacter pylori after omeprazole plus roxithromycin treatment; Cellini L et al.; The in vitro antibacterial activity of omeprazole against eight strains of Helicobacter pylori was evaluated . Minimum inhibitory concentration (MIC) values were 32 micrograms/ml and 64 micrograms/ml (MIC50 and MIC90 respectively) . We performed a randomized single blind study comparing the efficacy of omeprazole alone (for 4 weeks) or combined with roxithromycin (for 2 weeks) in the treatment of duodenal ulcer and chronic active gastritis associated with H . pylori infection, H . pylori was eradicated in 75% of patients treated with omeprazole alone whereas the patients treated with the combination of these drugs were completely free from H . pylori at the end of the therapy.

Immun Infekt, 1991 Dec, 19(6), 175 - 8
{Bases of the antibacterial effect of beta lactam antibiotics}; Hof H; The primary antibacterial effect of betalactam antibiotics is due to the inhibition of cell-wall synthesis . Prerequisites for good antibacterial activity of such an antibiotic are --rapid penetration across the bacterial cell wall, --strong binding to the proper targets in the cytoplasmic membrane, i.e . the penicillin-binding proteins, --resistance to betalactamases which may be produced by the bacterial cell.

Int Dent J, 1991 Dec, 41(6), 348 - 58
Multiple medication: problems of the elderly patient; Oh VM; Elderly persons are apt to receive multiple drugs for many diseases . Prescribers should take extra care in persons aged over 65-70 years, and especially the very old . The main problem of the elderly is the unpredictability of their response to drugs . Self-medication with both prescribed and over-the-counter drugs worsens this problem . Drug actions may be altered by impairment of the liver, kidneys and brain, or acute illness, or both . Unwanted (adverse) drug reactions often produce rapid and unduly severe illness in the old . Some antibacterial antibiotics like the sulphonamides are best avoided . Taking many drugs together promotes adverse interactions between the drugs . Drugs with a narrow therapeutic ratio, such as warfarin, digoxin, the aminoglycosides, and many antiarrhythmic drugs, cause clinical problems . Old persons respond more abruptly to drugs like benzodiazepines, opioid analgesics, and antiparkinsonian drugs . Anaesthesia given on top of psychotropic drugs may damage the central nervous system . The elderly brain is more sensitive to induction agents and short-acting intravenous anaesthetics, like alfentanil and midazolam; the elderly liver is more easily damaged by inhalational anaesthetics like halothane . The overall benefit:risk ratio should be judged for every drug in each patient . Wherever possible, drug treatment should be avoided . If drugs are given, safe drugs with broad therapeutic ratios and tissue- or receptor-specific actions are preferable . Drug doses are usually, but not always, reduced . Benefit from a drug should be assessed early . Severe unpredictable adverse reactions need immediate cessation of the drug and prompt patient support . The practitioner should frequently review the patient's continuing need for drugs.

Jpn J Antibiot, 1991 Dec, 44(12), 1392 - 6
{Pharmacokinetics of cefodizime in patients undergoing hemodialysis}; Itagaki N et al.; The object of this study was to establish the most effective regimen of cefodizime (CDZM) for patients with chronic renal failure undergoing hemodialysis (HD) . T 1/2 beta of CDZM upon 1 g intravenous administration was 3.50 +/- 0.72 hours in an on-HD group, and it was 11.26 +/- 3.89 hours in an off-HD group . When CDZM was administered consecutively at a dose of 1 g or 2 g only after HD, the serum concentration of CDZM was maintained at levels sufficient to exert antibacterial activity, and no tendency for accumulation was observed . The most effective regimen of CDZM to HD patients, therefore, has been that in which concluded to administration was done only after completion of HD, in a dose of 1 g for mild infections and that of 2 g for severe infections.

Grud Serdechnososudistaia Khir, 1991 Dec, (12), 42 - 5
{Prognosis and prevention of post-traumatic pneumonia in closed thoracic injuries}; Murav'ev SM et al.; The authors elaborated the criteria of prognosticating the development of posttraumatic pneumonia on the basis of diagnostic information (clinical, radiological, endoscopic findings) gained in the first hours after hospitalization of patients with closed chest trauma, and compiled a prognostic table by means of which the probability of the development of pneumonia was appraised in 236 patients . Individual clinical prognostication allowed opportune and differentiated application of a complex of special therapeutic and preventive measures including, along with the traditional methods, the use of the possibilities of therapeutic endoscopy, modern antibacterial, physiotherapeutic, and immunocorrective treatment . The applied tactics made it possible to reduce posttraumatic pneumonia incidence and achieve its favourable course in most patients.

Bioessays, 1991 Dec, 13(12), 657 - 63
Insect antibacterial proteins: not just for insects and against bacteria; Kimbrell DA; In response to a bacterial infection, insects launch an array of countermeasures . Among these are the antibacterial proteins, which effectively lyse bacteria or are bacteriostatic . These proteins were generally assumed to be restricted to insects, yet recent information has shown some homologous counterparts in vertebrates, including humans . Recent data have revealed that at least some of these proteins can also act against eukaryotic cells, including human infectious parasites . The latter activities have opened up new possibilities for disease control.

J Dairy Sci, 1991 Dec, 74(12), 4137 - 42
Potent antibacterial peptides generated by pepsin digestion of bovine lactoferrin; Tomita M et al.; The antibacterial properties of enzymatic hydrolysates of bovine lactoferrin were examined to determine whether active peptides are produced from this protein . Hydrolysates prepared by cleavage of lactoferrin with porcine pepsin, cod pepsin, or acid protease from Penicillium duponti showed strong activity against Escherichia coli O111, whereas hydrolysates produced by trypsin, papain, or other neutral proteases were much less active . Low molecular weight peptides generated by porcine pepsin cleavage of lactoferrin showed broad-spectrum antibacterial activity, inhibiting the growth of a number of Gram-negative and Gram-positive species, including strains that were resistant to native lactoferrin . The antibacterial potency of the hydrolysate was at least eightfold greater than that of undigested lactoferrin with all strains tested . The active peptides retained their activity in the presence of added iron, unlike native lactoferrin . The effect of the hydrolysate was bactericidal as indicated by a rapid loss of viability of E . coli O111 . The lactoferrin hydrolysate described in the present study has commercial value as a natural preservative agent for use in foods and cosmetics, and as a functional component of new clinical foods for prevention or treatment of gastrointestinal disease.

Minerva Med, 1991 Dec, 82(12), 799 - 805
{Lactoferrin}; Iuliano R et al.; Lactoferrin is a protein present in many fluids of the human organism and in the secondary granules of polymorphonuclear cells (PMN) . In the blood stream lactoferrin favours the segregation of PMN by mediating and amplifying the immune response, and realizes a negative feedback control on the Colony Forming Unit Granulocyte/Macrophage (CFU-GM) proliferation . At intestinal level it promotes iron absorption and prevents bacterial overgrowth . The antibacterial effect of lactoferrin is used clinically to prevent bacterial infections in neutropenic patients submitted to chemotherapy for leukemic diseases type M1, M2, M4 and M5, according to FAB criteria . In patients affected by chronic pancreatitis the lactoferrin concentration, in duodenal juice, is found to be significantly higher than in normal subjects . This finding suggests a pathogenetic role of the protein in chronic pancreatitis.

J Antibiot (Tokyo), 1991 Dec, 44(12), 1394 - 405
Studies on condensed-heterocyclic azolium cephalosporins . II . Synthesis and antibacterial activity of 7 beta-{2-(2-aminothiazol-4-yl)-2(Z)-alkoxyiminoacetamido}-3-(condensed- heterocyclic azolium)methyl-3-cephem-4-carboxylates; Yoshimura Y et al.; From our series of studies on cephalosporins bearing condensed-heterocyclic azolium methyl groups at the 3 position in the cephalosporin nucleus, we describe here the synthesis and antibacterial activity of 7 beta-{2-(2-aminothiazol-4-yl)-2(Z)-alkoxyiminoacetamido}ceph alosporins containing imidazo{1,5-a}pyridinium, imidazo{1,2-b}pyridazinium, imidazo{1,2-a}pyrimidinium, imidazo{1,2-c}pyrimidinium, and pyrazolo{1,5-a}pyridinium methyl groups at the 3 position . Among the cephalosporins tested, 7 beta-{2-(2-aminothiazol-4-yl)-2(Z)-methoxyiminoacetamido}-3- (imidazo{1,5-a}pyridinium-2-yl) (1), (imidazo{1,2-b}pyridazinium-1-yl) (2), and (pyrazolo{1,5-a}-pyridinium-1-yl) (3)methyl-3-cephem-4-carboxylates showed potent antibacterial activity and broad antibacterial spectrum . The antibacterial activity of these cephalosporins (1 approximately 3) was superior to that of ceftazidime (CAZ) . These results imply that the delocalization of the positive charge of the imidazo{1,5-a}pyridinium, pyrazolo{1,5-a}pyridinium and imidazo{1,2-b}pyridazinium groups leads to an expanded antibacterial spectrum and increased activity and that these condensed-heterocyclic compounds as well as imidazo{1,2-a}pyridine are effective moieties for improving antibacterial activity and spectrum.

Int J Exp Pathol, 1991 Dec, 72(6), 623 - 30
Protective effect of tissue ferritins in experimental Escherichia coli infection of mice in vivo; Lipinski P et al.; The effect of ferritins from horse (FH) and bovine (FB) spleen and murine liver (FM) on the survival rate of CFW mice lethally infected with Escherichia coli (strain 8440-78 K 80/B) was evaluated . Ferritins given intravenously 24 h before intravenous inoculation of bacteria, protected mice most effectively from death due to infection . The effect was dose dependent . At 500 micrograms of ferritin per mouse, the maximum survival rates were 86% (FH), 81% (FM) and 79% (FB), while only 5% of the control mice survived up to the 30th day . The survival rates of animals injected with bovine serum albumin (BSA) and heat-inactivated FB were 8 and 25%, respectively . Intraperitoneal injection of FB was as effective as intravenous in enhancing the resistance of mice against bacteria . These data provide evidence for the beneficial role of tissue ferritins in nonspecific antibacterial resistance.

J Med Chem, 1991 Dec, 34(12), 3390 - 5
Synthesis and antibacterial activities of C-21 functionalized derivatives of (9R)-9-amino-9-deoxoerythromycins A and B; Lartey PA et al.; Selective protection of (9R)-9-amino-9-deoxoerythromycin A allowed for elimination of the 12-hydroxyl group to afford a versatile 12,21-olefin intermediate . Further modifications of the intermediate led to the syntheses of (9R)-9-deoxo-9-(N,N-dimethylamino)-12,21-epoxyerythromycin B, (9R)-9-deoxo-9-(N,N-dimethylamino)-21-hydroxyerythromycin A, and (9R)-9-deoxo-9-(N,N-dimethylamino)-21-hydroxyerythromycin B . All three compounds retained antibacterial activity against several organisms normally susceptible to (9R)-9-deoxo-9-(N,N-dimethylamino)erythromycin A . However, the 21-hydroxylated erythromycin A analogue was weaker in potency than the corresponding erythromycin B congener and much weaker than the epoxy derivative . This suggests that while substitution of a polar functionality at C-21 does not abolish antibacterial activity, introduction of vicinal polar groups at both C-12 and C-21 may lead to reduction in potency . Nevertheless, these 21-functionalized derivatives of (9R)-erythromycylamine provide an entry into novel analogues of the important macrolide antibiotic erythromycin.

Klin Med (Mosk), 1991 Dec, 69(12), 63 - 7
{Clinical-biochemical parallels in various methods of proteinase inhibitor kontrykal administration to patients with nonspecific lung diseases}; Provotorov VM et al.; Changes in clinical manifestations, activity of kinin blood system, serum alpha 1-proteinase inhibitor and proteinase-inhibitory system of bronchial lavage were evaluated in patients with acute pulmonary abscess in the presence of chronic bronchitis and lingering pneumonia treated locally (intrapulmonary and endobronchial administration) and conventionally with antibacterial and antiproteolytic drugs . Forty patients with acute pulmonary abscess and chronic bronchitis and 49 with the abscess and pneumonia received multimodality treatment including intrapulmonary and endobronchial introduction of antibiotics and contrykal . Thirty-five abscess patients with chronic bronchitis and 52 such with lingering pneumonia received intravenous droplet contrykal in identical day dose . Clinico-biochemical follow-up results were indicative of local contrykal advantages as the patients stayed in hospital for a shorter period, did not develop complications and chronic forms of nonspecific pulmonary diseases.

Antimicrob Agents Chemother, 1991 Dec, 35(12), 2505 - 8
Effect of protein binding of daptomycin on MIC and antibacterial activity; Lee BL et al.; A higher rate of clinical failures in patients treated with daptomycin (2 mg/kg of body weight, given once daily) compared with rates in patients treated with conventional regimens caused early termination of this comparative clinical trial . One explanation for these failures could be that daptomycin is highly protein bound and that the concentration of the unbound active drug is too low for antibacterial activity . To assess this explanation, we studied the binding of daptomycin to proteins by using an ultrafiltration method . pH (7.0 to 7.4), temperature (25 or 37 degrees C), or daily freezing and thawing over 2 months had no effect on binding of daptomycin to proteins . We found that daptomycin was bound to albumin (90%) at 4 g/100 ml . Binding of daptomycin was not concentration dependent (2.5 to 80 micrograms/ml) . In human serum samples spiked with daptomycin, average binding was 94% +/- 2.4% . In 6 subjects given an intravenous infusion of daptomycin (3 mg/kg), average binding was 90% +/- 2.1% . Susceptibility studies showed that a concentration in serum 20 times the unbound concentration was needed to equal the MIC of the total drug . These results indicate that daptomycin is highly bound (90 to 94%) to albumin and that clinical failure to daptomycin can in part be explained by the low concentration of the unbound drug.

Biochemistry, 1991 Nov 12, 30(45), 10895 - 904
Construction of a synthetic gene for an R-plasmid-encoded dihydrofolate reductase and studies on the role of the N-terminus in the protein; Reece LJ et al.; R67 dihydrofolate reductase (DHFR) is a novel protein that provides clinical resistance to the antibacterial drug trimethoprim . The crystal structure of a dimeric form of R67 DHFR indicates the first 16 amino acids are disordered {Matthews et al . (1986) Biochemistry 25, 4194-4204} . To investigate whether these amino acids are necessary for protein function, the first 16 N-terminal residues have been cleaved off by chymotrypsin . The truncated protein is fully active with kcat = 1.3 s-1, Km(NADPH) = 3.0 microM, and Km(dihydrofolate) = 5.8 microM . This result suggests the functional core of the protein resides in the beta-barrel structure defined by residues 27-78 . To study this protein further, synthetic genes coding for full-length and truncated R67 DHFRs were constructed . Surprisingly, the gene coding for truncated R67 DHFR does not produce protein in vivo or confer trimethoprim resistance upon Escherichia coli . Therefore, the relative stabilities of native and truncated R67 DHFR were investigated by equilibrium unfolding studies . Unfolding of dimeric native R67 DHFR is protein concentration dependent and can be described by a two-state model involving native dimer and unfolded monomer . Using absorbance, fluorescence, and circular dichroism techniques, an average delta GH2O of 13.9 kcal mol-1 is found for native R67 DHFR . In contrast, an average delta GH2O of 11.3 kcal mol-1 is observed for truncated R67 DHFR . These results indicate native R67 DHFR is 2.6 kcal mol-1 more stable than truncated protein . This stability difference may be part of the reason why protein from the truncated gene is not found in vivo in E . coli.

Eur J Biochem, 1991 Nov 1, 201(3), 661 - 74
Tricholongins BI and BII, 19-residue peptaibols from Trichoderma longibrachiatum . Solution structure from two-dimensional NMR spectroscopy; Rebuffat S et al.; Two nonadecapeptides, tricholongins BI and BII, which display antifungal and antibacterial activities, have been isolated from in vitro cultures of the fungus Trichoderma longibrachiatum . The peptides were separated by reversed-phase HPLC; their amino acid compositions were determined by gas chromatography and their sequences by positive-ion fast-atom-bombardment mass spectrometry and high-field NMR . These linear peptides, containing mainly hydrophobic L-amino acids, 8-9 2-aminoisobutyric acid residues and exhibiting an acetylated N-terminal residue and an amino alcohol C-terminal leucinol belong to the peptaibol class . The methanol solution structure of tricholongins BI and BII has been investigated using both one- and two-dimensional NMR techniques . The total 1H-NMR and 13C-NMR assignments are given . By a combination of the 3JNH,C alpha H coupling constant values, temperature coefficients of the NH and CO groups, amide hydrogen/deuterium-exchange rate measurements and NOE data, a secondary structure for tricholongins in solution has been proposed . Both peptides adopt a similar alpha-helical conformation with a hinge around Pro13 resulting from two 3(10) bonds . The results suggest that the N-terminus contains mixed alpha/3(10) bonds . The membrane permeability modifications induced by tricholongins have been assayed by the use of liposomes composed of egg phosphatidylcholine with 20-30% cholesterol . The peptide-induced leakage of an entrapped fluorescent probe has been followed by fluorescence spectroscopy . In a concentration range of 0.13-0.31 microM, tricholongins induce the leakage of 50% of the entrapped material in 20 min.

Dis Mon, 1991 Nov, 37(11), 669 - 746
Inflammatory bowel disease . Part II: Clinical and therapeutic aspects; Kirsner JB; Once regarded as medical curiosities, ulcerative colitis and Crohn's disease have achieved a remarkable change in status recently and today are among the more compelling of all human illnesses . The cause(s) of inflammatory bowel disease (IBD) are not known . Genetic, environmental, microbial, and immunologic factors are involved, but the precise mechanisms are obscure . The incidence of ulcerative colitis is relatively stable, while Crohn's disease continues to increase in frequency . In 10% to 15% of patients, it is hard to differentiate between ulcerative colitis and Crohn's colitis, however, problems with diagnosis usually resolve with time and repeated examinations . In part I of his two-part monograph on IBD, Dr . Kirsner addressed the nature and pathogenesis of the disease . Increased study of ulcerative colitis and Crohn's disease in recent years has generated new knowledge regarding their etiology . Part I focused on microbial, immunologic, and genetic mechanisms of, and the inflammatory process involved in the disease . In this part, Dr . Kirsner deals with the clinical features, course, and management of IBD, based on the author's 55 years of experience with these problems and supplemented by critical examination of the recent (1988-1990) literature . Particular attention is directed to the symptoms and physical findings of ulcerative colitis and Crohn's disease . The laboratory, radiologic, endoscopic, and pathologic features, and the many systemic complications . IBDs are mimicked by several enterocolonic infections and other conditions making differential diagnosis necessary . Inflammatory bowel disease in children and the elderly conforms to conventional clinical patterns modified by the health circumstances of the respective age groups . Because the cause of IBD has not been established, current medical therapy is facilitative and supportive rather than curative . The principles of medical treatment are approximately the same for ulcerative colitis and Crohn's disease . Treatment emphasizes a program rather than a drug and also considers the individuality of the therapeutic response . A clearer understanding of dietary and nutritional needs, including hyperalimentation and electrolyte and fluid balance, aids treatment . Antidiarrheal and antispasmodal preparation and sedatives are prescribed for symptom relief . The bowel inflammation is controlled with sulfasalazine or the newer 5-amino-salicylic acid (5-ASA) compounds, antibacterial drugs for complications of Crohn's disease and IBD, adrenocortical steroids, and the immunosuppressive compounds 6-mercaptopurine (6MP), azathioprine, and cyclosporine, as determined in each patient . The surgical procedures available for treatment of ulcerative colitis include total proctocolectomy and ileostomy or ileoanal anastomosis.(ABSTRACT TRUNCATED AT 400 WORDS)

Infection, 1991 Nov-Dec, 19(6), 462 - 4
Prophylaxis with ofloxacin in patients with cancer and neutropenia; Maiche AG; The suppression of potentially pathogenic microorganisms using prophylactic antibacterial treatment could eventually protect the patient from infection . Oral absorbable and non-absorbable antibacterial agents have been used with variable results . In the present study, 47 patients with cancer and neutropenia received oral ofloxacin 200 mg twice daily prophylactically . All patients were previously treated with antineoplastic chemotherapy . Septicemia developed in ten patients (21%) . The number of infections was higher in patients with a level of granulocytopenia under 0.5 x 10(9)/1 . Infection was caused in almost all patients by gram-positive organisms . Prophylaxis with ofloxacin provided efficacious protection against gram-negative bacteria and was well tolerated.

Farmaco, 1991 Nov, 46(11), 1337 - 50
Synthesis, antibacterial activity and structure-activity relationships of N-substituted 4-diazo-pyrazole-5-carboxamides . 2; Baraldi PG et al.; A series of 4-diazopyrazole-5-carboxamides 1 d-n has been synthesized and their antibacterial activity against a number of Gram-negative and Gram-positive strains has been tested . Some of the compounds resulted quite active and the whole set allowed to further study the SAR of the class . Substituents in position 5 affect Gram-negative and Gram-positive activities via bulk and electronic properties respectively; position 3 mostly affects the Gram-negative activity, while the presence of the charged diazo group in position 4 is crucial for both antibacterial activities.

Stomatologiia (Mosk), 1991 Nov-Dec, (6), 48 - 50
{The morphological characteristics of the interaction of parietal microflora with the mucosal epitheliocytes of the alveolar crest in patients with partially missing teeth}; Zufarov SA et al.; Microbiopsy specimens of the alveolar ridge obtained at the sites of missing teeth from patients and similar autopsy specimens from those dead without apparent oral and gastrointestinal diseases were examined electron microscopically in order to elucidate the interactions between the oral mucosa parietal microflora and epitheliocytes . Cocci-like microorganisms and microorganisms resembling Candida-like yeast by their ultrastructure were as a rule seen on the surface of the horny layer . The results evidence that loss of teeth involves the appearance of quite a number of various parietal bacteria in the oral mucosa, inducing characteristic changes in the pricky and horny layer cells . Intracellular location of the bacteria also contributes here . All this should be borne in mind when choosing the denture design . Antibacterial therapy appears to be advisable before fitting the patients with dentures.

Vestn Otorinolaringol, 1991 Nov-Dec, (6), 28 - 31
{Characteristics of postoperative period in surgical treatment of chronic frontal sinusitis}; Skopina EL et al.; During the last 5 years 132 patients underwent frontal-ethmoidal trepanation . Recurrences were observed in 27 (20%) patients with nonspecific immune deficiency, frequent respiratory viral infections and microbial virulence . The major cause of recurrences was inadequacy of the frontal-nasal ostium . Recurrences occurred more frequently in patients with orbital and intracranial complications of frontitis, traumatic frontitis, and abnormal anatomic relations of the frontal and ethmoidal sinuses . It is recommended to carry out postoperative conservative therapy including antibacterial, antiedematous, desensitizing drugs as well as drugs stabilizing immunity and microcirculation . It is also recommended to follow-up patients during a year after frontal-ethmoidal trepanation because recurrent episodes occur mostly during this time period.

Int J Pancreatol, 1991 Nov-Dec, 10(3-4), 293 - 7
Antibacterial and mezlocillin-enhancing activity of pure human pancreatic fluid; Bassi C et al.; The majority of deaths in severe pancreatitis are the result of superinfection of necrotic tissue . The pathogen most commonly responsible for such infections is Escherichia coli . Antibiotic prophylaxis would appear a logical precaution . The antibacterial drugs of choice should possess two basic characteristics: they must be active against the flora responsible for the infections and must be capable of penetrating into the pancreas at adequate minimum inhibitory concentrations (MICs) . Mezlocillin--which is active against E . coli--has been shown to possess the latter requisite, but achieving therapeutic concentrations requires administration at high doses . In the present study, pure human pancreatic fluid showed properties similar to those observed in the dog against E . coli (bacterial colony growth 100 times lower than in a control culture) and produced a 75% reduction in mezlocillin MICs against this organism . These enhancing characteristics might make the commonly used doses sufficient for prophylactic purposes.

Khirurgiia (Mosk), 1991 Nov, (11), 5 - 9
{Acute cholecystogenic suppurative cholangitis}; Gostishchev VK et al.; The authors discuss the results of clinical, instrumental, and microbiological examinations of 240 patients suffering from purulent cholangitis in acute cholecystitis . Choledocholithiasis was the main cause of the development of purulent cholangitis in 90.8% of patients . A classification of cholangitis and the clinical signs of the disease are dwelt upon . Endoscopic decompression of the biliary tract in the preoperative period is an obligatory condition for performing laparotomic operation . A complex of detoxification measures and general and local (prolonged flow dialysis of the biliary tract) antibacterial therapy are indicated in the postoperative period . All the measures led to decrease of mortality rates in cholecystogenic purulent cholangitis from 19.5 to 6.2%.

J Dairy Sci, 1991 Nov, 74(11), 3724 - 30
Potent bactericidal activity of bovine lactoferrin hydrolysate produced by heat treatment at acidic pH; Saito H et al.; A hydrolysate of bovine lactoferrin produced by heat treatment under acidic conditions had antibacterial activity at concentrations of 10 micrograms/ml in the culture medium . The optimal degree of hydrolysis for this activity was about 10% . Heat-treated lactoferrin, treated at pH 2.0 and 120 degrees C for 15 min and degree of hydrolysis of about 10%, had no Fe-binding capacity (0%) and less antigenicity (about 10(-6) than untreated lactoferrin . Heat-treated lactoferrin increased in antibacterial activity, and the activity was maintained in an Fe-rich medium . After fractionation of heat-treated lactoferrin by reverse-phase HPLC, several peptide fractions were found that had strong antibacterial activity . It was suggested that lactoferrin latently contains at least one bactericidal domain that is activated upon release by limited acid hydrolysis of the protein . The bactericidal activity of the peptide fragments of lactoferrin was shown to have no relation to Fe chelation, in contrast with the antibacterial mechanism of native lactoferrin.

Gut, 1991 Nov, 32(11), 1291 - 4
Long term serological surveillance after treatment of Helicobacter pylori infection; Veenendaal RA et al.; Fifteen patients with type B gastritis caused by Helicobacter pylori infection were treated with 'triple' therapy consisting of colloidal bismuth subcitrate, amoxycillin, and metronidazole . All were followed up as outpatients every three months for at least one year . After 'triple' therapy a significant (p less than 0.01) and persistent reduction in IgA and IgG antibody levels against H pylori was detected . In three patients recurrent active infection with H pylori at nine and 12 months was detected by a rise in IgA (three patients) and IgG (two patients) antibody levels against H pylori and worsening of symptoms, and was confirmed by culture and histology . In 11 patients, the absence of infection at 12 months was confirmed by culture and histology . In a control group of 13 patients with type B gastritis who received no antibacterial treatment, specific IgA and IgG antibody levels against H pylori remained unchanged during 12 months of follow up . Although specific IgG against H pylori is the most widely used serological test for screening, our data indicate that specific IgA is also valuable in monitoring treatment . These serological tests are easy to perform, relatively inexpensive, devoid of radioactivity and are very acceptable to patients . It is concluded that serological testing is the preferred method for follow up after treatment for H pylori infection and will probably replace endoscopy or the urea breath test.

Cesk Farm, 1991 Nov, 40(4-5), 145 - 7
{Synthesis and antibacterial activity of thiosemicarbazones of 3-acylquinolones}; Radl S et al.; Oxidation of 3-acetyl derivatives of 3-acetyl-1-ethyl-1,4-dihydro-6,7-methylenedioxyquinoline-4-one (VIc) and 3-acetyl-7-chloro-1-ethyl-6-fluoro-1,4-dihydroquinoline-4-one (VId) with selenium dioxide provided the corresponding acids, {1-ethyl-1,4-dihydro-6,7-methylenedioxy-4-oxoquinoline-3-yl}glyoxylic acid (VIe) and {7-chloro-1-ethyl-6-fluoro-1,4-dihydro-4-oxoquinoline-3-yl}glyoxylic acid (VIf), respectively . Reactions of compounds VIc--VIf with thiosemicarbazide yielded the respective thiosemicarbazones of 3-acetyl-1-ethyl-1,4-dihydro-6,7-methylenedioxyquinoline-4-one (VIIa), 3-acetyl-7-chloro-1-ethyl-6-fluoro-1,4-dihydroquinoline-4-one (VIIb), {1-ethyl-1,4-dihydro-6,7-methylenedioxy-4-oxoquinoline-3-yl}glyoxylic acids (VIId) . The compounds showed no significant in vitro antibacterial activity.

Photochem Photobiol, 1991 Nov, 54(5), 661 - 6
Type I and type II photosensitization by the antibacterial drug nalidixic acid . A laser flash photolysis study; Vermeersch G et al.; The 355 nm laser flash photolysis of nalidixic acid at pH 9.2 leads to the formation of the nalidixate anion triplet state (absorption lambda max = 620 nm; 5700 less than or equal to epsilon T less than or equal to 9000 M-1cm-1; 0.6 less than or equal to phi T less than or equal to 1) . The first order triplet state decay (kT = 7.7 x 10(3) s-1) is accompanied by a diffusion controlled triplet-triplet annihilation . Oxygen efficiently quenches the triplet state (k = 3.2 x 10(9) M-1s-1) . The nalidixate radical dianion (absorption lambda max = 650 nm; epsilon = 3000 M-1cm-1) is produced by the diffusion controlled reductive quenching of the triplet state by tryptophan and tyrosine . The superoxide anion (O2-.) is produced by diffusion controlled reaction of the radical dianion with oxygen . The O2- . is characterized by its reactions with ferricytochrome c and superoxide dismutase . The physiological form of nalidixic acid is thus a good Type I and Type II photosensitizer.

Toxicol Appl Pharmacol, 1991 Nov, 111(2), 221 - 32
Mechanistic studies of the phototoxic potential of PD 117596, a quinolone antibacterial compound; Robertson DG et al.; PD 117596 is a novel quinolone compound that is being investigated for use as an antibacterial agent . Early investigations demonstrated a significant phototoxic liability associated with this compound . These studies were undertaken to investigate the mechanism of phototoxicity using an in vitro model . In the UVA region, PD 117596 was found to be a more efficient producer of singlet oxygen than rose bengal, ciprofloxacin, nalidixic acid, or PD 118879, another quinolone under investigation . The quantum yield of photoreaction for PD 117596 was relatively low (phi = 0.021); however, it was approximately 10-fold higher than other tested quinolones . In vitro studies using a mouse erythrocyte model were used to further investigate the mechanism of phototoxicity . PD 117596-induced photohemolysis was found to be oxygen dependent with a relatively rapid onset that progressed even after removal of light . Preirradiation of the compound prevented subsequent hemolytic or photohemolytic action . BHA, BHT, alpha-tocopherol, and the iron chelator DTPA were all found to be effective at ameliorating the photohemolytic response . The photohemolytic response was markedly enhanced when D2O was substituted for H2O in the incubation medium, indicating a singlet oxygen-mediated mechanism of action . A rise in thiobarbituric acid products was noted within 1 hr of irradiation and was maximal at the time of onset of overt photohemolysis . These data suggest that singlet oxygen production by irradiated PD 117596 is responsible for secondary changes in mouse red blood cells including lipid peroxidation and ultimately results in cellular lysis.

J Biol Chem, 1991 Oct 25, 266(30), 19890 - 3
Trimethoprim binds in a bacterial mode to the wild-type and E30D mutant of mouse dihydrofolate reductase; Groom CR et al.; Previous crystallographic studies of the antibacterial trimethoprim in complexes with bacterial and avian dihydrofolate reductases have shown substantial differences in the mode of binding, providing plausible explanations for the origin of the remarkable species selectivity of this inhibitor (Matthews, D . A., Bolin, J . T., Burridge, J . M., Filman, D . J., Volz, K . W., Kaufman, B . T., Beddell, C . R., Champness, J . N., Stammers, D . K., and Kraut, J . (1985) J . Biol . Chem . 260, 381-391; Matthews, D . A., Bolin, J . T., Burridge, J . M., Filman, D . J., Volz, K . W., and Kraut, J . (1985) J . Biol . Chem . 260, 392-399) . A major species difference between the active sites is that the only carboxylate present is always Glu in vertebrates and Asp in bacteria . Crystallographic studies of the wild-type and E30D mutant of the enzyme from mouse now reveal that in both cases trimethoprim is bound in an identical fashion to that observed with the bacterial enzyme, and there is no obvious single explanation for the origin of the 10(5)-fold selectivity of trimethoprim binding . In an earlier study of a mouse wild-type enzyme using more limited data it was proposed that trimethoprim bound in the avian mode (Stammers, D . K., Champness, J . N., Beddell, C . R., Dann, J . G., Eliopoulos, E . E., Geddes, A . J., Ogg, D., and North, A . C . T . (1987) FEBS Lett . 218, 178-184), but a re-examination indicates that the occupancy of the active site by trimethoprim is less than had been thought, and we are currently unable to make an unambiguous interpretation of the electron density maps and cannot confirm the avian mode of binding in those crystals.

Sci Total Environ, 1991 Oct 15, 108(3), 275 - 83
Fate and microbiological effects of furazolidone in a marine aquaculture sediment; Samuelsen OB et al.; Furazolidone is used in the treatment of bacterial diseases in farmed fish . During application a large proportion of the administered drug reaches the environment directly or via feces . The persistence and metabolism of furazolidone in sediment from a Norwegian salmon farm is described . Furazolidone, in contrast to oxytetracycline and oxolinic acid, is actively metabolized by microorganisms in the sediment . The main metabolite is 3-(4-cyano-2-oxobutylidene-amino)-2-oxazolidone . This is a well known metabolite of the degradation of furazolidone in mammals, fish and Escherichia coli . 3-(4-Cyano-2-oxobutylideneamino)-2- oxazolidone had no detectable antibacterial activity . The half-life of furazolidone in the sediment at 4 degrees C was calculated to be 18 h.

J Antibiot (Tokyo), 1991 Oct, 44(10), 1073 - 82
Synthesis and biological activity of novel 3-(2-propenyl)-cephalosporins . I; Kim WJ et al.; The synthesis, antibacterial activity and oral absorption of novel cephalosporins (3a-3d) having a 2-propenyl group at the C-3 position are described . Diphenylmethyl 7-amino-3-(2-propenyl)-3-cephem-4-carboxylate HCl (4) prepared from 7-aminocephalosporanic acid in 12 steps was acylated with various acid moieties to give cephems 3a-3d . The cephems 3a-3c showed similar antibacterial activities as cefixime . However, these cephems were not well absorbed orally.

Toxicol Lett, 1991 Oct, 58(2), 215 - 23
Quinolone antibacterial-agent-induced cutaneous phototoxicity: ear swelling reactions in Balb/c mice; Wagai N et al.; The phototoxic potentials of quinolone derivatives and the possibility of free radical contribution to their phototoxicity were investigated by measuring increments in ear thickness . Balb/c mice, fasted overnight, were orally administered ofloxacin (OFLX), lomefloxacin (LMFX), enoxacin (ENX), ciprofloxacin (CPFX) and DR-3355 (the s-isomer of OFLX), and immediately exposed to ultraviolet-A light (UVA: 320-400 nm) for 4 h (21.6 joules/cm2) . Measurement of ear thickness was carried out 0, 24 and 48 h after the end of irradiation . The time-course profiles of ear thickness varied with both the doses and the quinolone used, but linear dose-response curves were obtained from the data 24 h after irradiation ended . The 50% ear thickness increment-inducing doses of LMFX, ENX, OFLX, CPFX and DR-3355 were calculated as 24.8, 81.9, 428.0, 457.9 and 526.6 mg/kg, respectively . The phototoxic potential of these quinolones coincided with the data obtained previously by measuring the incidence of erythema on the ears . Pretreatment with butylated hydroxtoluene, a free radical scavenger, almost completely prevented all swelling reactions induced by the quinolones . These results suggest that the degree of phototoxicity induced by the quinolones used could depend on the balance between the generation of free radicals and the effectiveness of the defense systems against toxic radicals.

Int Dent J, 1991 Oct, 41(5), 279 - 86
Role of chlorhexidine in the management of dental caries; Kidd EA; Chlorhexidine has a role in the management of patients with a high level of disease, but it is not a universal panacea for caries control . This paper reviews the antibacterial activity and mode of action of this antiseptic and presents the evidence supporting its use in caries control . Current clinical applications are suggested and the methods of application described.

Am J Ophthalmol, 1991 Oct, 112(4 Suppl), 34S - 47S
Clinical evaluation of ciprofloxacin 0.3% ophthalmic solution for treatment of bacterial keratitis; Leibowitz HM; A multicenter, prospective clinical study of 148 culture-proven cases of bacterial keratitis, treated with ciprofloxacin 0.3% ophthalmic solution, compared its clinical and antibacterial efficacy with the standard therapy regimen of each investigator . Most often, this consisted of topically administered fortified cefazolin (33 mg/ml) and fortified gentamicin or tobramycin (14 mg/ml) . Two control groups were studied: (1) patients treated while the ciprofloxacin study was ongoing (not enrolled group); and (2) patients treated during the year before initiation of the ciprofloxacin study (historical group) . Treatment with ciprofloxacin yielded a 91.9% success rate . Standard therapy yielded an 88.2% success rate among not enrolled control patients and an 88.3% success rate among the historical control patients . No serious side effects accompanied ciprofloxacin administration . In vitro susceptibility testing showed ciprofloxacin to be highly effective against bacterial corneal pathogens . These findings suggest that ciprofloxacin 0.3% is safe and effective as a single agent for the treatment of bacterial keratitis.

Am J Ophthalmol, 1991 Oct, 112(4 Suppl), 29S - 33S
Antibacterial effectiveness of ciprofloxacin 0.3% ophthalmic solution in the treatment of bacterial conjunctivitis; Leibowitz HM; Two hundred eighty-eight cases of culture-proven bacterial conjunctivities were evaluated as part of two multicentered, randomized, prospective clinical studies comparing the antibacterial efficacy of topically administered ciprofloxacin 0.3% either with a placebo or with tobramycin 0.3% . In the first study, ciprofloxacin was significantly (P less than .001) more effective than the placebo . It eradicated or reduced the various bacterial pathogens in 93.6% of patients, compared to 59.5% for the placebo . In the second study, ciprofloxacin (94.5%) and tobramycin (91.9%) were equally effective . Topically applied ciprofloxacin eradicated or reduced all isolated bacterial species, attesting to its broad antibacterial spectrum and its potential usefulness in treating external ocular infections.

Dis Mon, 1991 Oct, 37(10), 605 - 66
Inflammatory bowel disease . Part I: Nature and pathogenesis; Kirsner JB; Once regarded as medical curiosities, ulcerative colitis and Crohn's disease have achieved a remarkable change in status recently and today are among the more compelling of all human illnesses . The cause(s) of inflammatory bowel disease (IBD) are not known . Genetic, environmental, microbial, and immunologic factors are involved, but the precise mechanisms are obscure . The incidence of ulcerative colitis is relatively stable, while Crohn's disease continues to increase in frequency . In 10% to 15% of patients, it is hard to differentiate between ulcerative colitis and Crohn's colitis; however, problems with diagnosis usually resolve with time and repeated examinations . In part I of his two-part monograph on IBD, Dr . Kirsner addresses the nature and pathogenesis of the disease . Increased study of ulcerative colitis and Crohn's disease in recent years has generated new knowledge regarding their etiology . Part I focuses on microbial, immunologic, and genetic mechanisms and the inflammatory processes involved in the disease . In part II, which will be presented in next month's issue of Disease-a-Month, Dr . Kirsner deals with the clinical features, course, and management of IBD, based on the author's 55 years of experience with these problems and supplemented by critical examination of the recent (1988-1990) literature . Particular attention is directed to the symptoms and physical findings of ulcerative colitis and Crohn's disease, the laboratory, radiologic, endoscopic, and pathologic features, and the many systemic complications . The IBDs are mimicked by several enterocolonic infections and other conditions, making differential diagnosis necessary . Inflammatory bowel disease in children and the elderly conforms to conventional clinical patterns modified by the health circumstances of the respective age groups . Because the cause of IBD has not been established, current medical therapy is facilitative and supportive rather than curative . The principles of medical treatment are approximately the same for ulcerative colitis and Crohn's disease . Treatment emphasizes a program rather than a drug and also considers the individuality of the therapeutic response . A clearer understanding of dietary and nutritional needs, including hyperalimentation and electrolyte and fluid balance, aids treatment . Antidiarrheal and antispasmodic preparations and sedatives are prescribed for symptom relief . The bowel inflammation is controlled with sulfasalazine or the newer 5-amino salicylic acid (5-ASA) compounds, antibacterial drugs for complications of Crohn's disease and IBD, adrenocortical steroids, and the immunosuppressive compounds 6-mercaptopurine (6-MP), azathioprine, and cyclosporine, as determined in each patient . The surgical procedures available for treatment of ulcerative colitis include total proctocolectomy and ileostomy or ileoanal anastomosis.(ABSTRACT TRUNCATED AT 400 WORDS)

Proc Natl Sci Counc Repub China B, 1991 Oct, 15(4), 251 - 65
Production of beta-lactam antibiotics and its regulation; Demain AL; The discovery of penicillin was announced over 60 years ago . It was the first beta-lactam antibiotic and the importance of this group is greater today than it has ever been . It is clear that even at 60 years of age, beta-lactams are going strong and no one contemplates their early retirement . Currently, sales of beta-lactam compounds form the largest share by far of the world's antibiotic market . The beta-lactam antibiotics include penicillins such as penicillin G, penicillin V, ampicillin, cloxacillin, and piperacillin; cephalosporins such as cephalothin, cephaloridine, cephalexin, and cefaclor; and cephamycins such as cefoxitin . In addition, beta-lactam antibiotics include the more recently developed nonclassical structures such as monobactams, including aztreonam; clavulanic acid, which is a component of the combination drug augmentin; and thienamycin, which is chemically transformed into imipenem, a component of the combination drug known as primaxin (or tienam) . The classical beta-lactam antibiotics can be divided into hydrophobic and hydrophilic fermentation products . The hydrophobic members, e.g . benzylpenicillin (penicillin G) and phenoxymethylpenicillin (penicillin V), contain non-polar side chains, e.g . phenylacetate and phenoxyacetate, respectively, and are made only by filamentous fungi; the best known of these is Penicillium chrysogenum . The antibacterial spectrum of the hydrophobic penicillins is essentially Gram-positive . The hydrophilic types are penicillin N, cephalosporins and 7-alpha-methoxycephalosporins (cephamycins) which are made by fungi, actinomycetes and unicellular bacteria . They all contain the polar side chain, D-alpha-aminoadipate . We can draw a sequence of reactions which describes the biosynthesis of all penicillins and cephalosporins, however the total sequence exists in no one microorganism . All penicillin and cephalosporin biosynthetic pathways possess the first three steps in common and all cephalosporin pathways go through deacetylcephalosporin C . However, there are many subsequent biosynthetic reactions which vary in the different producing organisms . Production of beta-lactam antibiotics occurs best under conditions of nutrient imbalance and at low growth rates . Nutrient imbalance can be brought about by limitation of the carbon, nitrogen or phosphorus source . In addition to these factors, amino acids such as lysine and methionine exert marked effects on production of penicillins and/or cephalosporins by some microorganisms . Induction of some of the synthetases, especially the first enzyme, ACV synthetase, by methionine is the basis of the methionine stimulation of cephalosporin C synthesis in C . acremonium . Inhibition of homocitrate synthase is the mechanism involved in lysine inhibition of penicillin synthesis in Penicillium chrysogenum.(ABSTRACT TRUNCATED AT 400 WORDS)

Dent Mater, 1991 Oct, 7(4), 217 - 24
A study of the relationship among pulpal response, microbial microleakage, and particle heterogeneity in a glass-ionomer-base material; Plant CG et al.; This investigation was designed to study the pulpal responses to glass-ionomer base materials that differ in particle size distribution . The study was carried out according to the BSI (1980) recommendations for testing restorative materials in vivo . The base materials caused more pulpal inflammation than the control material, Kalzinol, although by an indirect mechanism . A significant association was demonstrated in the statistical model between bacterial presence within the experimental cavity and pulpal inflammation . The type of restorative material has no direct association with the degree of inflammation, although the model suggests that it exerts an indirect influence via its antibacterial properties, and hence its influence on microbial microleakage . The base material, with a heterogeneous particle distribution, was associated with greater bacterial microleakage . Particle size distribution, therefore, has some effect upon bacterial microleakage, but, because of its complex effect upon several physical properties of materials, further studies are indicated.

Am J Dent, 1991 Oct, 4(5), 226 - 30
The fluid-filled gap under amalgam and resin composite restorations; Ben-Amar A et al.; This article discusses the factors involved in the formation of marginal gaps between amalgam or resin composite restorative materials and cavity walls . The fluid that penetrates the microspace from the oral cavity and from the dentinal tubules is followed by bacterial invasion . This process can lead to secondary caries and irritation of the dentin/pulp complex . The bacterial growth is controlled by effective sealing at the tooth/restoration interface, partial obliteration of the gap, accumulation of solids at the cavosurface margins of the restorations, and by antibacterial linings.

Bratisl Lek Listy, 1991 Oct, 92(10), 496 - 503
{Side effects and toxicity of new quinolones}; Krcmery V et al.; A review paper is presented treating of problems of organotoxicity, mutagenicity, carcinogenicity and adverse effects of quinolones, as well as their interaction with other drugs . Not considering some rather sporadic exceptions, quinolones are not regarded as safe in children up to the age of 14 and in pregnant and breast-feeding women . Compared to aminoglycosides, tetracycline, chloramphenicol, rifampicin and other antibacterial chemotherapeutics, the overall toxicity of quinolones is relatively low . The questions of adverse effects upon the intestinal microflora and of tolerance of novel quinolones are also addressed . With regard to the above mentioned aspects, ofloxanice, ciprofloxacine, enoxacine, pefloxacine, norfloxacine, and fleroxacine have been most thoroughly studied . For the other recently developed quinolones reliable information is scarce . (Tab . 2, Ref . 53).

Antibiot Khimioter, 1991 Oct, 36(10), 23 - 5
{Comparative characteristics of biological properties of Francisella tularensis strains isolated in the USSR}; Pavlovich NV et al.; With a large collection of the strains of F . tularensis isolated it has been recently shown that cultures belonging to holarctica and mediaasiatica circulate in the endemic foci of the USSR . By their biological and genetic properties the natural strains of F . tularensis were homogeneous and represented type cultures of F . tularensis . Various ecological conditions in the natural environment did not change within the last 20 years the sensitivity of the tularemia microbe to the antibacterial drugs.

Biull Eksp Biol Med, 1991 Oct, 112(10), 441 - 4
{Morphological reaction of various tissues and organs on the administration of the occluding material "Rabrom"}; Savvina TV et al.; A new occlusive X-Ray opaque antibacterial substance of biological origin was experimented on rats and dogs . The substance was administered intraperitoneally, intrahepatically and on the soft tissues of the limbs . Morphological studies conducted showed accumulation of macrophages.

Acta Neurol (Napoli), 1991 Oct, 13(5), 424 - 32
Alprazolam enhances the antibacterial activity exerted by normal human peripheral blood lymphocytes; Covelli V et al.; The effects of two benzodiazepines, diazepam and alprazolam, have been evaluated on the in vitro antibacterial activity exerted by human peripheral blood lymphocytes (PBL) . Results demonstrate that diazepam has no influence on this PBL function, while alprazolam is able to enhance this activity in six out of nine normal donors considered . The possible therapeutical implications of these data are discussed.

Acta Neurol (Napoli), 1991 Oct, 13(5), 418 - 23
Effects of benzodiazepines on the immune system; Covelli V et al.; Benzodiazepines (BDZ) are psychotropic drugs largely used in patients with affective disorders . As far as their effects on the immune system are concerned, a few studies have been carried out until now . Diazepam is inhibitory in vitro for the phagocytic functions and the antibody synthesis, being its action mediated via specific receptors on immunocompetent cells . On the contrary, alprazolam results to be enhancing for the antibacterial activity exerted by normal human peripheral blood T lymphocytes in vitro . Taken together, these data point out the different role which BDZ play on the immune response.

Antimicrob Agents Chemother, 1991 Oct, 35(10), 2085 - 90
Single daily dosing of antibiotics: importance of in vitro killing rate, serum half-life, and protein binding; Potel G et al.; The relative importance of pharmacokinetic and pharmacodynamic parameters for the feasibility of a single daily dose (SDD) of antibiotics remains to be established . Therefore, we studied the relationship between in vitro bacteriological parameters (MIC, MBC, and killing rate {KR}, defined as the reduction in the inoculum within 3 h), pharmacokinetic parameters (t1/2 and protein binding {PB}, and in vivo antibacterial effect of a single antibiotic dose in an experimental rabbit model of Escherichia coli endocarditis . Nine antibiotics were investigated: two aminoglycosides, two quinolones, and five beta-lactams . For each drug, the minimal effective dose (MED) (in milligrams per kilogram) was defined as the lowest dose able to achieve a significant difference (P less than 0.05) of CFU in the vegetations in comparison with controls 24 h after a single intravenous injection . Aminoglycosides and quinolones had the lowest MEDs, followed by beta-lactams . Univariate regression analysis showed that KR was the major determinant of MED . A stepwise regression analysis showed that t1/2 significantly improved the predictive value of KR, while PB, MIC, and MBC did not . The final equation was MED = 1,586-238 KR-297 t1/2 (r = 0.90, P = 0.01) . We concluded that the pharmacodynamic parameters (especially the high KR) of aminoglycosides and quinolones explained their low MEDs and might allow SDD . In contrast, the low KR of beta-lactams emphasized the critical importance of a long t1/2, as for ceftriaxone, allowing the use of this beta-lactam alone in SDD.

Biochem Pharmacol, 1991 Sep 27, 42(8), 1595 - 9
DNA base damage by beta-lactam, tetracycline, bacitracin and rifamycin antibacterial antibiotics; Quinlan GJ et al.; Several antibacterial antibiotics have been shown to participate with transition metal ions in chemical reactions leading to the formation of reactive oxygen species . An important host defence mechanism for dealing with invading bacteria involves the production of reactive oxygen species, such as superoxide, hydrogen peroxide and hypochlorous acid, by phagocytic cells . The production of reactive oxygens by redox cycling antibacterial antibiotics has led us to suggest that a 'phagomimetic' contribution may also be made in vivo . Here we show that four structurally different antibacterial antibiotics, in the presence of added copper salt, bring about oxidative modification to bases in DNA detected using gas chromatography-mass spectrometry . The drug most damaging to DNA was rifamycin SV which was more active than a reference mixture of hydrogen peroxide and ascorbic acid.

J Chromatogr, 1991 Sep 27, 558(1), 155 - 73
Determination of sulfonamides by liquid chromatography, ultraviolet diode array detection and ion-spray tandem mass spectrometry with application to cultured salmon flesh; Pleasance S et al.; Ion-spray mass spectrometry was investigated for the analysis of 21 antibacterial sulfonamide drugs . All of the sulfonamides analyzed gave positive ion mass spectra with abundant protonated molecules and no fragmentation . Tandem mass spectrometry (MS-MS) using collision-induced dissociation provided structural information, allowing the identification of common fragmentation pathways and the differentiation of isomeric and isobaric sulfonamides . A reversed-phase high-performance liquid chromatographic method was developed, using gradient elution and ultraviolet diode-array detection (DAD), enabling the separation of 16 of the sulfonamides . Combined liquid chromatography (LC)-MS was accomplished using the ion-spray interface . Analyses of a mixture of sulfonamide standards were performed with gradient elution and the mass spectrometer configured for full-scan acquisition, selected-ion monitoring, or selected-reaction monitoring . Procedures for the analysis of sulfadimethoxine (SDM), a representative sulfonamide used in the aquaculture industry, are described . The presence of SDM in cultured salmon flesh was confirmed at levels as low as 25 ng/g by a combination of LC-DAD and LC-MS-MS.

Am J Med, 1991 Sep 12, 91(3A), 5S - 11S
Tissue-directed pharmacokinetics; Schentag JJ et al.; Azalide antibiotics demonstrate pharmacokinetics distinct from all antibacterial agents in common use . Following oral absorption, conventional oral antibiotics diffuse through serum and interstitial compartments and are eliminated rapidly . A minimal to moderate degree of intracellular penetration may be observed . The pharmacokinetics of azithromycin, the first azalide, are characterized by a rapid and extensive movement of the drug from the serum into intracellular compartments . A dynamic equilibrium exists between the intracellular, interstitial, and serum compartments, with predominant flux into tissue sites . Azithromycin is concentrated to a high degree within phagocytes and transported by chemotactic mechanisms to the site of infection . High concentrations of azithromycin are found in pulmonary, genital, and lymphatic tissues . Azithromycin's serum levels decline in a polyphasic manner with a terminal half-life of approximately 60 hours . These kinetics allow azithromycin to be administered once daily . It is predicted that after drug administration for 5 days, therapeutic levels of azithromycin will be maintained at the tissue sites of infection for an additional 4-7 days . Consideration of the extravascular pharmacodynamics of azithromycin is necessary when making predictions regarding its therapeutic application.

FEBS Lett, 1991 Sep 9, 289(2), 167 - 70
Involvement of sapecin in embryonic cell proliferation of Sarcophaga peregrina (flesh fly); Komano H et al.; Addition of antibodies against sapecin to the culture medium of NIH-Sape-4 cells derived from a Sarcophaga embryo greatly inhibited cell proliferation, whereas addition of sapecin stimulated cell proliferation . These results suggest that sapecin is involved in the proliferation of embryonic cells of Sarcophaga . Sapecin is known to have potent antibacterial activity, so it seems to have two different biological functions: i.e . protection against bacterial infection and stimulation of embryonic cell proliferation.

Vet Microbiol, 1991 Sep, 29(1), 49 - 58
Bactericidal potency and mechanistic specificity of neutrophil defensins against bovine mastitis pathogens; Cullor JS et al.; Two neutrophil defensins, rabbit peptides NP-1 and NP-5, were examined for their in vitro antibacterial activity against a panel of Gram-positive and Gram-negative organisms isolated from mastitic cows . Incubation for 60 minutes with 5 micrograms/ml of NP-1 in 10 mM sodium phosphate buffer resulted in substantial killing (greater than 95%) of all organisms tested . Although NP-5 was virtually inactive under these same conditions, supplementation of the incubation mixture with dilute nutrient media sensitized otherwise resistant organisms to this defensin . For both NP-1 and NP-5, bactericidal activity was dependent on time and concentration . Our findings demonstrate that the spectrum of defensin bactericidal activities include clinically important bovine pathogens . Further, the data demonstrate that NP-1 and NP-5, peptides which are homologous in 18 of their 33 residue positions, possess distinct mechanisms of action.

Int J Dermatol, 1991 Sep, 30(9), 667 - 9
Naftifine treatment of trichomycosis pubis; Rosen T et al.; Naftifine hydrochloride 1% cream is a recently developed material of proven efficacy in superficial cutaneous fungal infections . The drug has also been reported to have significant antibacterial properties as well . A case of trichomycosis pubis, a bacterial disorder that can easily be mistaken for several fungal diseases, responded to application of naftifine cream . The authors suggest that this medication may be the drug of choice when the clinical presentation consists of nodules encircling pubic or axillary hair.

J Trauma, 1991 Sep, 31(9), 1181 - 202
The relationship between mechanisms of wounding and principles of treatment of missile wounds; Mendelson JA; Determinants of the wounding effects of a metallic projectile include the velocity, mass, shape, and stability of the missile, and whether it tumbles, deforms, or fragments within the body . The velocity, mass, shape, and stability influence its capability to penetrate through the skin, and the other factors influence the depth and volume of the wound . The energy lost into the tissues (kinetic energy deposition) is a greater determinant of potential wound volume than is the striking velocity, even though, because K.E . = 1/2 MV2, the potential striking K.E . is more strongly influenced by velocity than mass . The actual size and shape of the wound is influenced by tumbling, deformation, and fragmentation of the projectile and by the characteristics of the tissues and organs contacted . The pulsating temporary cavitation resulting from the passage of a high-velocity projectile produces blunt trauma that extends beyond the tissue actually contacted by the missile . The pulsation of the temporary cavitation with resulting strong negative pressure components permits contamination of the entire wound track of a perforating wound, with entrance of external contaminants from both the exit and the entrance sites . The extent and type of treatment required is determined more by the tissues and organs injured than by the characteristics of the wounding agent . Although extremity wounds from high-velocity projectiles may heal uneventfully, surgical exploration is indicated whenever there is a possibility of subfascial penetration, and obviously devascularized tissue should be excised . In circumstances in which contaminated devascularized tissue cannot be excised promptly or adequately, prophylactic topical antibacterial therapy (such as mafenide aqueous spray, which can penetrate through devascularized tissue) may prevent otherwise lethal infection.

Acta Radiol, 1991 Sep, 32(5), 415 - 20
Powdered diatrizoic acid for radiography of the respiratory tract . Part I . Experimental investigation; Szmigielski W et al.; Powdered diatrizoic acid as a contrast medium administered by inhalation and insufflation for visualization of the airways was tested in vitro and in 21 dogs . Good radiopacity of the contrast medium and its antibacterial activity was found in vitro . In the majority of animal experiments visualization of the bronchial tree down to segmental and partially to subsegmental bronchi with only minimal agglomeration of contrast medium and with good or very good demonstration of anatomic details was achieved . In the majority of dogs contrast medium was eliminated from the lungs within 18 hours . Arterial blood gases tested on 5 dogs showed only unimportant changes after contrast medium administration . No adverse reactions were observed . Histologic and ultrastructural examinations after contrast studies showed phagocytic reaction to diatrizoic acid, transient impairment of production of surfactant, reactive changes of bronchial mucosa, and no fibrotic changes in the long-term observation.

J Med Chem, 1991 Sep, 34(9), 2857 - 64
Dual-action cephalosporins: cephalosporin 3'-quinolone carbamates; Albrecht HA et al.; A series of cephalosporins has been prepared in which the 3'-position was linked to the nitrogen of the antibacterial quinolone ciprofloxacin through a carbamate function . Like the ester-linked and quaternary-linked dual-action cephalosporins reported earlier, these carbamate-linked compounds exhibited a broad antibacterial spectrum derived from both cephalosporin-like and quinolone-like activities, suggesting a dual mode of action . Studies to elucidate details of the mechanism of action have been inconclusive . Ciprofloxacin liberated as a consequence of bacterial enzyme-mediated reactions may contribute to the second mode of action, although some evidence indicates that the intact carbamate-linked bifunctional molecules may possess intrinsically both beta-lactam and quinolone activities.

Postgrad Med, 1991 Sep 1, 90(3), 153 - 64, 167
Choosing the right antibacterial agent . Is 'newer' always better?
Anderson DJ.
The newer antibacterials are proving in some situations to be more effective than the older agents, and it is tempting to choose them . In many instances, however, traditional agents remain the treatment of choice . Major drawbacks of using newer antibacterials include their higher cost by weight, compared with older drugs, and the emergence of resistant organisms or superinfection as a result of overuse . The newer drugs are best reserved for use when older agents would be inadequate.

Mutat Res, 1991 Sep, 258(2), 123 - 60
The genetic toxicology of acridines; Ferguson LR et al.; Acridine and its derivatives are planar polycyclic aromatic molecules which bind tightly but reversibly to DNA by intercalation, but do not usually covalently interact with it . Acridines have a broad spectrum of biological activities, and a number of derivatives are widely used as antibacterial, antiprotozoal and anticancer drugs . Simple acridines show activity as frameshift mutagens, especially in bacteriophage and bacterial assays, by virtue of their intercalative DNA-binding ability . Acridines bearing additional fused aromatic rings (benzacridines) show little activity as frameshift mutagens, but interact covalently with DNA following metabolic activation (forming predominantly base-pair substitution mutations) . Compounds where the acridine acts as a carrier to target alkylating agents to DNA (e.g . the ICR compounds) cause predominantly frameshift as well as base-pair substitution mutations in both bacterial and mammalian cells . Nitroacridines may act as simple acridines or (following nitro group reduction) as alkylating agents, depending upon the position of the nitro group . Acridine-based topoisomerase II inhibitors, although frameshift mutagens in bacteria and bacteriophage systems, are primarily chromosomal mutagens in mammalian cells . These mutagenic activities are important, since the compounds have considerable potential as clinical antitumour drugs . Although evidence suggests that simple acridines are not animal or human carcinogens, a number of the derived compounds are highly active in this capacity.

Farmakol Toksikol, 1991 Sep-Oct, 54(5), 36 - 40
{Ferakril--a local-action hemostatic}; Annenkova VZ et al.; The data of the preclinical and clinical study of feracryl, a local hemostatic, are presented . The drug's hemostatic activity, acute, subacute and chronic toxicity, anesthetic effect as well as antibacterial and antifungal activities were studied . The results of the clinical trial of the drug are given.

Tsitol Genet, 1991 Sep-Oct, 25(5), 45 - 9
{Genotoxic effects of molybdenum and its derivatives in an experiment on Drosophila and mammals}; Chopikashvili LV et al.; As a result of research it is established that molybdenum shows the most pronounced genetic activity at the early stages of spermatogenesis . Genetic effects of molybdenum and its modification by vitamin S are registered in the test of dominant lethal mutations . The cytogenetic activity of molybdenum, the molybdenic candle-end and its modification by antibacterial preparation have been revealed in the cells of mammalian marrow.

Arch Pharm (Weinheim), 1991 Sep, 324(9), 537 - 42
Imidazo{4,5-b}pyridine derivatives of potential tuberculostatic activity, II: Synthesis and bioactivity of designed and some other 2-cyanomethylimidazo{4,5-b}pyridine derivatives; Bukowski L et al.; Based on the analysis of Quantitative Structure--Activity Relationships (QSAR) three representatives of imidazo{4,5-b}pyridine derivatives of predicted high antibacterial activity against Mycobacterium tuberculosis were synthetized and tested bacteriologically . Excellent agreement of the predicted and experimentally observed bioactivity was noted . Additional new derivatives of 4-methyl-4H-2-cyanomethylimidazo{4,5-b}pyridine (7) and 2-(alpha-methylcyanomethyl)imidazo{4,5-b}pyridine (22) were also synthesized and some of them were tested for tuberculostatic activity . The compounds synthesized according to a standard "trial and error" approach appeared generally inactive.

Agents Actions, 1991 Sep, 34(1-2), 274 - 7
Structural and functional organization 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 polymorphonuclear leukocytes (PMN), two fragments representing roughly the two halves of the BPI molecule . The 25 kDa N-terminal fragment possesses all the antibacterial activities of the 60 kDa parent protein, while the ca . 30 kDa C-terminal fragment has no detectable activity . The 25 kDa fragment is as potent on a molar basis 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 . The findings suggest that all of the molecular determinants of the antibacterial properties of BPI reside within the N-terminal half of the molecule, implying a novel structural/functional organization for a cytotoxic protein.

Vestn Otorinolaringol, 1991 Sep-Oct, (5), 8 - 11
{Therapeutic tactics in isolated and combined exudative ethmoid sinusitis in children}; Senchenko LS et al.; This paper presents the results of treatment of 81 children, aged 5 to 14 years, suffering from exudation ethmoid sinusitis; isolated ethmoid sinusitis was diagnosed in 17.8% and ethmoid sinusitis combined with maxillary sinusitis was detected in 61.7% cases . Most sinusitis cases (82.7%) were diagnosed in 5 to 10 year-old children . The ethmoidal labyrinth and maxillary sinus were treated by the puncture method, infection of other paranasal sinuses being excluded by the application of antibacterial, enzymic, corticosteroid drugs, immune agents, and adenotomy . Antibiotic therapy of 2 weeks in duration applied to the ethmoid labyrinth and maxillary sinus was more efficient when compared to the sinus treatment alone . The stable clinical effect was seen in 86.4% cases . This therapeutic approach can find application in practical otolaryngology.

J Burn Care Rehabil, 1991 Sep-Oct, 12(5), 420 - 4
Bactericidal and wound-healing properties of sodium hypochlorite solutions: the 1991 Lindberg Award; Heggers JP et al.; Toxic effects of sodium hypochlorite on wound healing elements have been confined to a restricted range of sodium hypochlorite concentrations . We investigated concentrations of sodium hypochlorite for antibacterial activity and tissue toxicity at varying time intervals . We attempted to find the efficacious therapeutic concentration that was both microbicidal and nontoxic . Gram-negative and gram-positive isolates (0.1/ml of 1 x 10(8)/ml) were introduced into various concentrations of buffered and unbuffered sodium hypochlorite solutions for determinations of bactericidal activity at 5-, 10-, 15-, and 30-minute intervals . Concentrations of sodium hypochlorite were 0.25%, 0.025%, and 0.0125% . In vitro assays with fibroblasts at the same concentrations were also performed to determine toxicity at the same time intervals . An in vivo incisional model was also used to determine the effects of sodium hypochlorite therapy on wound healing . Bactericidal effects were observed for concentrations as low as 0.025% . Tissue toxicity, both in vitro and in vivo, was observed at concentrations of 0.25% but not at a concentration of 0.025% . Although concentrations below this level were nontoxic, they were not bactericidal . Therefore a modified "Dakin's" solution at a concentration of 0.025% is therapeutically efficacious as a fluid dressing, since it preserves bactericidal properties and eliminates the detrimental potential on wound healing.

Infect Immun, 1991 Sep, 59(9), 3040 - 5
Attacin, an antibacterial protein from Hyalophora cecropia, inhibits synthesis of outer membrane proteins in Escherichia coli by interfering with omp gene transcription; Carlsson A et al.; Attacins are antibacterial proteins synthesized by pupae of the giant silk moth, Hyalophora cecropia, in response to a bacterial infection . In this report we show that the previously described, attacin-induced alteration in the structure and the permeability of the outer membrane of Escherichia coli is associated with a specific inhibition of the synthesis of several outer membrane proteins, including OmpC, OmpF, OmpA, and LamB . The inhibition is expressed as a reduction in the steady-state mRNA levels and is at least in part the results of a block in transcription of the corresponding genes . Transcription directed by the promoter of ompR, the positive regulator of ompC and ompF expression in response to environmental conditions, is also affected by attacin . The effects on mutant strains show that the primary activity of attacin is not mediated by the ompR-envZ regulatory system . Instead our data suggest the existence in E . coli of a previously unknown system for the transcriptional regulation of a large set of outer membrane proteins previously not known to be coordinately regulated . We propose that the activity of attacin is directed towards this system.

J Hosp Infect, 1991 Sep, 19 Suppl A, 47 - 59
The future role and importance of macrolides; Ball P; The new macrolides, notably clarithromycin and azithromycin, are significant advances over previous agents . With an extended antibacterial spectrum, increased activity, improved absorption and excellent tissue and intracellular penetration, they realize therapeutic aims which have been increasingly sought in the 1980s . They are likely to find an extended role in respiratory tract infections, especially in community-acquired pneumonia, where the activity against beta-lactam-resistant bacteria and intracellular pathogens, e.g . Mycoplasma pneumoniae, Legionella spp . and Chlamydia pneumoniae have a significant role to play . Realistic twice or once daily dosing will prove a powerful argument for their use and the major improvement in gastrointestinal tolerance compared with erythromycin is likely to prove a deciding factor in their favour.

Ann Intern Med, 1991 Aug 15, 115(4), 315 - 20
Scientific evidence versus therapeutic demand: the introduction of the sulfonamides revisited; Lerner BH; Because of recent changes in Federal Food and Drug Administration (FDA) regulations, new medications may now be marketed before completion of rigorous controlled testing . In order to understand the ramifications of this development, it is instructive to recall the introduction of the sulfonamides in the 1930s . The sulfonamides, the first effective antibacterial agents, were marketed in an era of relatively few regulations . Although investigators at times designed controlled trials to evaluate use of the drugs, both researchers and practitioners generally prescribed them for severe infections, despite a lack of conclusive data as to their efficacy . The clinical usefulness of sulfonamides for a given condition often became known through uncontrolled case studies and comparisons with historical control groups . Given the relaxation of FDA regulations, this method of drug evaluation may again become more commonplace.

Nucleic Acids Res, 1991 Aug 11, 19(15), 4059 - 65
HP 0.35, a cephalosporin degradation product is a specific inhibitor of lentiviral RNAses H; Hafkemeyer P et al.; Penicillins, cephalosporins and other betalactam antibiotics are widely used antibacterial drugs . Recently it was found that some of them also have effects on proliferating eukaryotic cells (Neftel, K.A . and Hubscher, U . (1987) Antimicrob . Agents Chemother . 31, 1657-1661), and one such effect was shown to be the inhibition of DNA polymerase alpha (Huynh Do,U., Neftel, K.A., Spadari, S . and Hubscher, U . (1987) Nucl . Acids Res . 15, 10495-10506) . The data suggested that degradation products of betalactam antibiotics were responsible for the inhibitory effect on DNA polymerase alpha . There is some confirmation at the structural level, since we found that penicillin binding proteins, the natural target of the cephalosporins, share amino-acid homologies to DNA polymerases and also to reverse transcriptase from HIV1 (Hafkemeyer, P., Neftel, K.A . and Hubscher, U . Meth . Find . Exp . Clin . Pharmacol . 12, 43-46, 1990) . We have purified and determined the structure of one product from the cephalosporin Ceftazidim and found one molecule (HP 0.35) that did not interfere with eukaryotic cell proliferation but rather had a specific inhibitory effect on the RNase H activity of human immunodeficiency virus 1 (HIV1) and feline immunodeficiency virus (FIV) reverse transcriptases, while the DNA polymerising activity of these enzymes was not affected . RNases H from HeLa cells, calf thymus and Escherichia coli on the other hand were much less affected by HP 0.35 . The inhibitory concentration of 50% (IC50) was more than 10 times lower compared to those of all cellular RNases H . We therefore tested the effect of HP 0.35 on in vitro lentivirus infection as exemplified by FIV-infection of CD(4+)-cat lymphocytes in cell culture . Under conditions where cell proliferation was absolutely unaffected, HP 0.35 was able to inhibit FIV-infection in CD(4+)-cat lymphocytes . Moreover, preincubation of these lymphocytes with HP 0.35 rendered the cells completely unsusceptible to FIV-infection . These data suggest that a degradation product of a clinically used betalactam antibiotic might represent an effective inhibitor class for lentiviral RNase H.

Curr Opin Oncol, 1991 Aug, 3(4), 643 - 7
Supportive care for viral infections in cancer patients; Gallagher J; Viral infections are more frequent and more severe in patients with cancer . As treatments for malignancy become ever more aggressive, the supportive care must also advance or the gains from innovative antineoplastic treatments will be lost to morbidity and mortality from secondary immune suppression and opportunistic infections . While empiric antibacterial and antifungal therapies for neutropenic leukemia patients were improving patients' survival, viral infections in cancer patients were often relegated to a clinical footnote in review articles since little could be done about them . Recently, however, acyclovir, ganciclovir, immunoglobulins, and ribavirin have given new opportunities for successful management of severe viral opportunistic infections in patients with leukemia and in bone marrow and other transplant patients.

J Antibiot (Tokyo), 1991 Aug, 44(8), 864 - 9
Cephalosporin antibiotics . II . Synthesis and biological properties of CS-461 and related compounds; Nakayama E et al.; The synthesis, structure-activity relationships, and biological properties of 3-thiazoliomethyl cephalosporins are described . 7-{2-(2-Aminothiazol-4-yl)-(Z)-2- methoxyiminoacetamido}-3-{5-(2-hydroxyethyl)-4-methylthiazoliomethyl+ ++}-3- cephem-4-carboxylate sulfate (CS-461) showed potent antibacterial activity against a wide variety of bacteria both in vitro and in vivo . Furthermore, CS-461 exhibited significantly low acute toxicity in mice.

J Antibiot (Tokyo), 1991 Aug, 44(8), 854 - 63
Cephalosporin antibiotics . I . Synthesis and structure-activity relationships of 3-thiazoliomethyl derivatives; Nakayama E et al.; The synthesis and the structure-activity relationships of 3-thiazoliomethyl cephalosporins are described . In a series of these parenteral compounds, 2-(2-aminothiazol-4-yl)-(Z)-2-methoxy-iminoacetamido group was found to be a favorable substituent for the C-7 position of the cephem nucleus . They showed potent antibacterial activity against both Gram-positive and Gram-negative bacteria including some beta-lactamase producing species.

J Antibiot (Tokyo), 1991 Aug, 44(8), 807 - 13
MM 55266 and MM 55268, glycopeptide antibiotics produced by a new strain of Amycolatopsis . Isolation, purification and structure determination; Box SJ et al.; Two novel glycopeptide antibiotics MM 55266 and MM 55268 containing fatty acid acyl functions, and of molecular formula C86H89N8O35Cl5 and C87H91N8O35Cl5, respectively, have been isolated and identified from a complex produced by Amycolatopsis sp . NCIB 40089 . Fermentation conditions for their production, and methods for their isolation are described . Structures have been deduced by use of COSY and NOE NMR techniques and supported by chemical degradation studies . Both glycopeptides possessed good antibacterial activity against Gram-positive organisms.

Curr Opin Rheumatol, 1991 Aug, 3(4), 581 - 5
Infectious agents and other nongenetic immunologic factors in spondyloarthropathies; Yu D et al.; Because one of the spondyloarthropathies, reactive arthritis, is induced by infections, research into the role of arthritis-causing bacteria has been strongly emphasized . The most remarkable finding in recent years is the detection of some of the bacterial components in the articular compartment, in some cases even several years after the development of arthritis . This location would account for the fact that T lymphocytes in the synovial compartment demonstrate a high in vitro response to preparations of the arthritis-causing bacteria . The persistence of these bacterial components would explain the frequently reported prolonged antibacterial antibody response in arthritis patients . Although the factors leading to the location and persistence of the bacteria are not clear, the finding provides a rationale for treating these patients with long-term antibiotics . A major question being investigated is how the presence of bacterial components in the articular compartment is related to the predominance of HLA-B27 in many of the patients.

Otolaryngol Clin North Am, 1991 Aug, 24(4), 813 - 27
The significance of experimental animal studies in otitis media; Juhn SK et al.; Animal models have been instrumental in investigating otitis media . Experimental models have allowed for focused research on how such factors as eustachian tube dysfunction and microbial infection contribute to the pathogenesis of otitis media . Antibacterial therapy and immunologic prophylaxis have been developed using these models . Current research is aimed at generating an objective index of middle ear inflammation for guiding patient management.

J Clin Invest, 1991 Aug, 88(2), 476 - 82
Human anti-phosphorylcholine antibodies share idiotopes and are self-binding; Halpern R et al.; We have previously shown that BALB/c antipneumococcal polysaccharide antibodies with phosphorylcholine (PC) specificity are self-binding, mediated by hypervariable sequence structure of the heavy chain . We extended the observation of self-binding anti-PC antibodies to naturally occurring human anti-PC antibodies . Anti-PC antibodies were purified from normal donor sera and shown to bind to monoclonal antiidiotypic anti-T15 antibodies originally raised against the murine T15 idiotype . These human antibodies are self-binding which is inhibitable by the PC hapten and the murine T15 (50-73)-derived Vh peptide . The anti-PC antibodies were further separated into id-positive and id-negative anti-PC antibodies . Only the T15 id-positive preparation was self-binding . These findings demonstrate an evolutionary, conserved biological property between mouse and man associated with a naturally occurring antibacterial antibody . This conserved biological and structural property may have been selected in evolution because it is part of an important immune defense mechanism against bacterial and other environmental pathogens.

Pediatrics, 1991 Aug, 88(2), 215 - 22
Randomized, controlled trial comparing long-term sulfonamide therapy to ventilation tubes for otitis media with effusion; Bernard PA et al.; Several studies have indicated that either the surgical insertion of ventilation tubes (VTs) or long-term treatment with sulfonamide-based antibacterials is effective in the management of otitis media with effusion (OME; otherwise known as serous otitis media, secretory otitis media, and glue ear) when compared with a no-treatment control or placebo . This controlled trial is the first to compare directly the effectiveness of these two treatments for long-standing OME . Outcome variables are treatment success rates, hearing thresholds, recurrent acute otitis media episodes, and side effects of medication or complications of VT placement . One hundred twenty-five children (aged 2.5 to 7 years) who met the usual indications for surgery (long-standing {greater than 3 months} OME and conductive hearing loss) were randomly assigned to "medical" treatment (sulfisoxazole 75 mg/kg per day for 6 months) or "surgical" treatment (bilateral insertion of VTs) . Subjects underwent pure-tone audiometry (500, 1000, 2000, 4000 Hz) and otomicroscopic examination at 2, 4, 6, 12, and 18 months . A significantly greater proportion of medical subjects (67%) than surgical subjects (48%) were treatment failures at 6, 12, or 18 months (P = .0208) . Surgical subjects had significantly better hearing at 2 and 4 months (P values less than .01) but not at 6, 12, and 18 months (P values greater than .2) . A significantly greater proportion of surgical subjects (50%) experienced complications of treatment than did medical subjects (9%) (P less than .001) . Thirty-three percent of candidates for VT placement did not require surgery when treated with a 6-month course of sulfisoxazole.(ABSTRACT TRUNCATED AT 250 WORDS)

J Antibiot (Tokyo), 1991 Aug, 44(8), 824 - 31
Hydramycin, a new antitumor antibiotic . Taxonomy, isolation, physico-chemical properties, structure and biological activity; Hanada M et al.; A new antitumor antibiotic hydramycin was isolated from the fermentation broth of Streptomyces violaceus P950-4 (ATCC 53807) . It showed potent antibacterial and cytotoxic activity and increased the survival time of mice inoculated with P388 leukemia . A new structure related to the pluramycin group antibiotics was assigned by its spectroscopic experiments.

Zhongguo Zhong Yao Za Zhi, 1991 Aug, 16(8), 451 - 3, 510
{Studies on the quality of fructus Cnidii--comparison of antibacterial action}; Cai J et al.; Comparative studies on antibacterial and antifungal action of the fruits of C . monnieri from four habitats and two other species of Cnidium showed they had inhibitory potency to some bacterial and fungi in vitro . C . monnieri and C . salium were more effective than C . dahuricum in antibacterial activities . C . monnieri had higher antifungal effect than C . salium and C . dahuricum.

Arzneimittelforschung, 1991 Aug, 41(8), 827 - 30
Studies on the antibacterial action of novel gem-diphenyl-spiro-cyclopropano- oxazolones and 2-aryl(alkyl)-4-ylidene-oxazol-5-ones; Lalitha N et al.; The preparation and in vitro antibacterial activity of a novel series of gem-diphenyl-spiro-cyclopropano-oxazolones (cis-1,2,2,5-tetraphenyl 6-oxa-4-azaspiro{2.4}hept-4-en-7-one) are described . The overall activity of these compounds was higher than that of the 2-aryl(alkyl)4-ylidene-oxazol-5-ones (azlactones) . The gem-diphenyl-spiro-cyclopropano-oxazolones 1-4 have emerged as the most potent derivatives when tested against bacteria.

Antibiot Khimioter, 1991 Aug, 36(8), 31 - 4
{Immunomodulating properties of pectin from seawater grass Zostera}; Zaporozhets TS et al.; Immunomodulating activity of zosterin was studied . Zosterin is a pectin from sea grass belonging to Zostera with pronounced antibacterial activity and therapeutic efficacy in experimental infections . It was shown that parenteral administration of the drug 24 hours before the antigenic irritation stimulated the humoral and cellular immunity in F1 (CBA X C 57 BL/6) mice: an increase in the number of the antibody cells in the spleen, the DTH and the index of the splenocyte spontaneous proliferation . In the animals treated with injections of zosterin and infected intraperitoneally with a virulent strain of S . enteritidis there was observed a marked increase in migration of polymorphonuclear leukocytes to the abdominal cavity accompanied by an increase in their phagocytic activity . The results suggested the possible use of zosterin as a drug with associated antibacterial and immunomodulating activities.

Eur J Clin Microbiol Infect Dis, 1991 Aug, 10(8), 613 - 7
The critical role of iron in some clinical infections; Bullen JJ et al.; The role of iron in certain clinical infections is revealed . In normal persons the antibacterial and antifungal properties of blood and other tissue fluids cannot be maintained unless there are exceptionally low levels of available iron . This is controlled by the presence of the unsaturated iron-binding proteins, transferrin and lactoferrin . In several clinical conditions an abnormal availability of iron is responsible for fatal septicaemia . This is because the phagocytic system is overwhelmed by rapidly growing organisms when iron is freely available.

Curr Opin Immunol, 1991 Aug, 3(4), 465 - 70
Role of T-cell subsets in bacterial infections; Kaufmann SH; Classic functional partitioning of T-cell subsets is being questioned: in many bacterial and protozoan infections, CD8 T cells play a role in protection; two types of CD4 T helper cells have been characterized, one protective, the other exacerbating disease; finally, gamma delta T cells have been implicated in the host response to certain bacteria . Moreover, evidence is accumulating that, in addition to T-cell helper functions, cytolytic T-cell functions participate in antibacterial immunity.

J Pharmacobiodyn, 1991 Aug, 14(8), 475 - 81
Transport of the new quinolone antibacterial agents of lomefloxacin and ofloxacin by rat erythrocytes, and its relation to the nicotinic acid transport system; Simanjuntak MT et al.; Transport mechanism of quinolonecarboxylic acid derivatives (quinolones), lomefloxacin and ofloxacin, in rat erythrocytes was investigated . The uptake of lomefloxacin by erythrocytes was apparently nonsaturable over the concentration range of 0.1-1.0 mM at 27 degrees C and pH 7.4 . In the case of ofloxacin, however, the erythrocytes took up ofloxacin in a concentration dependent manner at 20 degrees C and pH 7.4, with a maximum rate (Jmax) of 28.8 +/- 0.98 pmol/10(6) cells/s and a Michaelis constant (Kt) of 0.92 +/- 0.15 mM . An increase in the medium osmolarity caused a decrease in the {14C}lomefloxacin uptake, indicating that the drug is transported into the intracellular space of erythrocytes . The uptake of {14C}lomefloxacin by the erythrocytes was independent of pH but increased above pH 6.0, and, moreover, was dependent on temperature with an activation energy of 16.6 kcal/mol . The uptake of {14C}lomefloxacin was competitively inhibited by a water-soluble vitamin, nicotinic acid, with an inhibition constant (Ki) of 16.1 mM, but not inhibited by 10 mM of L-alanine, glucose, p-aminohippuric acid (PAH), N-methyl-nicotinamide (NMN) or tetraethylammonium chloride (TEA) . These lines of evidence suggest that the transport system of lomefloxacin and ofloxacin in rat erythrocytes is common with that of a water-soluble vitamin, nicotinic acid, to which quinolones are structurally analogous.

Eur J Biochem, 1991 Jul 15, 199(2), 285 - 91
Two-dimensional proton-NMR studies on a hybrid peptide between cecropin A and melittin . Resonance assignments and secondary structure; Sipos D et al.; A hybrid peptide of cecropin A and melittin was investigated by two-dimensional 1H-NMR at pH 5.8 in aqueous solution with 30% (by vol.) hexafluoroisopropanol . The peptide contains 26 amino acids, is a combination of the first 13 residues of each of the two parent peptides, CA(1-13)M(1-13) identical to CAM(1-26) and has an amidated C terminal . This peptide was recently synthesized {Boman, H.G., Wade, D., Boman, I.A., Wahlin, B . & Merrifield, R.B . (1989) FEBS Lett . 259, 103-106} and shown to have strong antibacterial activity but to be harmless towards erythrocytes . All resonances of the main chain and side chain beta-protons are assigned except for those of the N-terminal lysine . Several medium range NOE connectivities were observed showing two separated alpha-helices, involving residues 4-12 and 16-26 . The JNH alpha-coupling constants in these sections support the conclusion . From the exchange rates of the NH protons it is concluded that the alpha-helix of residues 16-26 is much more stable than the other helix . The circular dichroism data indicates about 30% less alpha-helix character than the NMR data . A reduced contribution to the ellipticity from the unstable helix is suggested . The chemical-shift differences between the two parts of the hybrid and the respective parent peptides are larger for the cecropin part than for the melittin part . For the latter, residues 17-26 of the hybrid are proposed to have a secondary structure very similar to that of residues 4-13 of melittin.(ABSTRACT TRUNCATED AT 250 WORDS)

Biochem Pharmacol, 1991 Jul 15, 42(3), 696 - 8
Glutathione transferase mu deficiency is not a marker for predisposition to sulphonamide toxicity; Riley RJ et al.; Glutathione transferase mu activity, a marker for susceptibility to lung cancer and chemically induced cytogenetic damage, is not a predictive index for the predisposition to sulphonamide hypersensitivity reactions . However, considering the functional diversity and broad, overlapping substrate specificity of GSH-dependent enzymes, it is conceivable that an as yet unidentified deficiency in another GST isozyme or GSH-related enzyme may be a marker for sulphonamide toxicity . In addition, heterogeneity in cellular repair mechanisms and the diversity of the human immune response {22} may also contribute to the manifestation of the toxic effects of sulphonamides . Experiments are currently in progress to determine which of this myriad of variables is predominantly responsible for inter-individual susceptibility to the idiosyncratic reactions produced by these antibacterial agents.

Eur J Biochem, 1991 Jul 15, 199(2), 435 - 9
Expression of post-translational processing of preprocecropin A using a baculovirus vector; Hellers M et al.; A cDNA fragment encoding preprocecropin A was inserted into the baculovirus Autographa californica nuclear polyhedrosis virus downstream of the polyhedrin promoter . The gene was expressed in recombinant-infected last instar larvae of Trichoplusia ni and in diapausing pupae of Hyalophora cecropia . The identity of the recombinant product was established by electrophoresis with detection of antibacterial activity and mass spectrometry . The prepropeptide had been correctly processed including removal of signal peptide and pro-part . Biologically active and amidated cecropin A was exported to the hemolymph . The yield of recombinant protein in H . cecropia reached a level of 600 micrograms/ml hemolymph and about 70% of the material was amidated.

Infect Immun, 1991 Jul, 59(7), 2396 - 402
Production of granulocyte-macrophage colony-stimulating factor (GM-CSF) by monocytes and large granular lymphocytes stimulated with Mycobacterium avium-M . intracellulare: activation of bactericidal activity by GM-CSF; Blanchard DK et al.; Treatment of monocytes with recombinant granulocyte-macrophage colony-stimulating factor (GM-CSF) was shown to enhance their antimycobacterial activity in an in vitro assay . Furthermore, Mycobacterium avium-M . intracellulare was found to induce the production of this hemopoietic growth factor . Human peripheral blood mononuclear cells were fractionated by plastic adherence and Percoll density centrifugation, and each population of cells was stimulated with mycobacteria . GM-CSF was produced by both monocytes and large granular lymphocytes (LGL) but not T lymphocytes . The phenotype of the GM-CSF-producing LGL was found to be CD2+, CD16+, and HLA-DR+ but negative for T-cell and monocyte markers . Kinetic studies demonstrated that GM-CSF appeared in the supernatant fluids within 2 days of culture of either monocytes or LGL and continued to be produced up to 7 days of incubation . Northern (RNA) blot analysis of RNA from both cell types demonstrated the expression of GM-CSF message within 24 h of stimulation . From these studies, LGL and monocytes are capable of responding to M . avium-M . intracellulare by producing factors that augment normal immune functions, including the antibacterial capability of monocytes.

Anesteziol Reanimatol, 1991 Jul-Aug, (4), 49 - 53
{The bacteriologic background and an analysis of the resistance of the agent to antibacterial preparations in patients in the postresuscitation period}; Erofeev VV et al.; A total of 6848 bacteriological passages have been performed in 57 patients during postresuscitation period under bacteriological monitoring that included the investigation of different body media twice daily . A microbial pattern has been compiled, typical of a certain intensive care unit, which served the basis for analysis of the resistance of the most widespread agents of pyoseptic complications to antibacterial preparations, with due consideration for the process site . The scheme of antibacterial therapy suggested made it possible to reduce the incidence of those complications due to the increased efficacy of antibacterial therapy in the postresuscitation period.

Zh Mikrobiol Epidemiol Immunobiol, 1991 Jul, (7), 5 - 8
{Escherichia coli reactions to the action of the cationic proteins of blood leukocytes}; Zhdan-Pushkina SM et al.; The antibacterial effect of cation proteins (CP) of swine leukocytes with respect to Escherichia coli strain 17 has been demonstrated in vitro . The composition and properties of these CP have been studied; as a result, a comparatively high content of basic and dicarbonic amino acids and the presence of protease activity have been established . The release of the components of the metabolic fund by E . coli under the influence of CP of swine leukocytes is indicative of changes in the permeability of microbial membranes and, probably, of the deficiency of energy resources . The addition of heparin to CP of swine leukocytes levels their antibacterial effect with respect to E . coli.

Klin Med (Mosk), 1991 Jul, 69(7), 89 - 90
{Effectiveness of bemitil in recurrent erysipelas}; Ratnikova LI; The trial entered 66 patients with recurrent erysipelas treated conventionally with addition of either immunostimulator bemitil (0.25-0.5 g/day orally for 5-7 days) or placebo . The bemitil group was free of intoxication symptoms and local manifestations, discharged from hospital sooner than the controls . Therapeutic efficacy of bemitil is due to its promotion of mononuclear phagocytes function which acts as an essential mechanism of antibacterial defence activation in patients with recurrent erysipelas.

Klin Med (Mosk), 1991 Jul, 69(7), 77 - 9
{Bacterial complications in acute hepatic failure in patients with hepatitis B}; Rakhmanova AG et al.; With virus hepatitis B (VHB) associated with acute hepatic insufficiency, precoma and coma, one third of the patients develop bacterial purulent inflammatory complications involving mainly biliary system and intestine . Attendant bacterial complications promoted rapid progression of hepatic coma seen commonly on day 1-10 of the disease . The diagnosis in relevant patients recognizing bacterial complications clinically should be based on alterations in the liver size, the presence of fever, elevated body temperature, relatively low decrease of prothrombin index and fibrinogen against leukocytosis with stab neutrophil shift . These symptoms call for introduction of antibacterial drugs.

J Ethnopharmacol, 1991 Jul, 33(3), 289 - 92
Traditional medicinal plants of Thailand . XVII . Biologically active constituents of Plumeria rubra; Hamburger MO et al.; The compounds 1-6 were isolated from the heartwood of Plumeria rubra, following bioactivity-directed fractionation . Plumericin 1 and isoplumericin 2 displayed molluscicidal, cytotoxic and antibacterial activity, 4-hydroxyacetophenone 3 was weakly cytotoxic, whereas the remaining glycosidic isolates (plumieride, 4; 13-O-coumaroylplumieride, 5; protoplumericine A, 6) were inactive in all test systems.

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