Pharmacology, 1995 May, 50(5), 333 - 7 Bismuth subcitrate and omeprazole inhibit Helicobacter pyloriF1-ATPase; Beil W et al.; The effects of various types of antiulcer agents against Helicobacter pylori F1-ATPase were studied . ATPase was released into the aqueous phase (i.e., solubilized) by sonication . The enzyme activity depended on Mg2+, but not Ca2+ . The maximum activity occurred at an ATP/Mg2+ ratio of 1/5 and at pH 7.5 . Mg(2+)-dependent ATPase activity was inhibited by sodium azide and the monovalent cations K+ and Na+, but not by oligomycin, dicyclohexylcarbodiimide, ouabain, or SCH 28080 . The antiulcer agents ranitidine, pirenzepine, aluminum hydroxide, and sucralfate failed to influence H . pylori F1-ATPase . In contrast, bismuth subcitrate and the H+/K(+)-ATPase inhibitor omeprazole inhibited the enzyme . Inhibition was prevented and reversed by the mercaptan glutathione, indicating that both drugs interfere with sulfhydryl groups of the enzyme . The data suggest that bismuth subcitrate and omeprazole owe their antibacterial activity against H . pylori, at least in part, to inhibition of F1-ATPase, an enzyme involved in bacterial energy metabolism. Toxicol Pathol, 1995 May-Jun, 23(3), 385 - 92 Histological examination on Achilles tendon lesions induced by quinolone antibacterial agents in juvenile rats; Kato M et al.; We examined the effects of the quinolone antibacterial agents pefloxacin (PFLX) and ofloxacin (OFLX) on the Achilles tendon of Sprague-Dawley rats . A single oral administration of PFLX 300 and 900 mg/kg or OFLX 900 mg/kg induced edema with mononuclear cell infiltration mainly in the inner sheath of the inner Achilles tendon just proximal to the tuber calcanei in rats killed on the next day . Cell infiltration was also seen in the adjacent synovial membrane and joint space . With progression of severity, the lesions extended to the surface tendon tissue, wherein irregularly arranged collagen bundles were detached from each other and nuclei of fibroblasts were pyknotic and fragmented . After 2-wk repeated administration, these lesions were replaced by fibrotic foci with regenerated tendon fibroblasts, and the incidence and severity were reduced in the OFLX but not PFLX groups . Coadministration of cyclosporin A with OFLX 300 mg/kg induced these lesions despite the fact that neither induced lesions alone . The tendon lesions were induced in juvenile rats (4 wk of age) but not in young adults (12 wk) . The articular cartilage of juvenile rats showed focal degeneration and/or cavitation in the tarsal joints after a single and 2-wk administration of PFLX or OFLX . Hydrocortisone slightly increased the incidence of OFLX-induced lesions in both the tendon and cartilage after a 2-wk administration . The occurrence of the tendon lesions is different from that of the Achilles tendon disorders reported in older humans, but they are thought to be a useful model for them. Ann Gastroenterol Hepatol (Paris), 1995 May-Jun, 31(3), 145 - 9 {Ileocecal tuberculosis . Apropos of 27 cases}; Mounadif M et al.; The authors report a retrospective study of 27 cases of "ileo-caecal tuberculosis" collected over a period of 10-years . Sixteen women and eleven men, between 14 and 55 years of age (with a group mean age of 28 years), were included . This is still a common disease in Morocco, despite attempts to achieve universal BCG vaccination . Diarrhoea, abdominal pain and a general physical deterioration are the most indicative signs, but are not specific . Tests for M . tuberculosis hominis are often negative, except in cases in which bacteria proliferate in pulmonary excavations, and this makes it difficult to establish a definite diagnosis . The detection of narrowing of the ileum or colon in a country where infection is endemic suggests the possibility of tuberculosis . Colonoscopy, which is becoming increasingly widespread in Morocco, makes an essential contribution . Although it is rare for caseum to be detected in biopsy fragments, the main value of histopathology is that it can eliminate cancer, making it possible to start antibacterial treatment without a diagnostic laparotomy . The outcome of medical treatment is nearly always positive . Clinical improvement, bacteriology tests and X-ray examinations are criteria that a cure has been obtained. Immunopharmacol Immunotoxicol, 1995 May, 17(2), 347 - 64 Evaluation of cellular immune responses and soluble mediators in patients with chronic hepatitis C virus (cHCV) infection; Jirillo E et al.; In 54 patients with cHCV infection, peripheral immune responsiveness and soluble mediator release were evaluated . Results demonstrate that in these patients phagocytosis and killing capacities exerted by polymorphonuclear cells and monocytes were profoundly depressed . At the same time, absolute numbers of CD3+, CD8+ and CD16+ cells were reduced, while the CD4(+)-CD8+ dependent antibacterial activity was also impaired . With special reference to soluble mediators, elevated amounts of both soluble interleukin-2 receptor and soluble intercellular adhesion molecule-1 were detected in sera of patients . By contrast, serum levels of tumor necrosis factor-alpha were within normal ranges, whereas interferon-gamma serum concentrations were decreased . Of note, in 18.5% of cHCV patients circulating levels of bacterial lipopolysaccharides (LPS) were detected by means of Limulus assay . In the Limulus+subset of patients, absolute numbers of CD14+ cells were reduced in a significant manner, this implying a putative monocyte-LPS interaction . In conclusion, the overall results indicate a condition of peripheral immune depression in cHCV patients with an exaggerated shedding of various mediators endowed with noxious effects for the host. Jpn J Antibiot, 1995 May, 48(5), 706 - 32 {General pharmacology of T-3761, a new oral quinolone antibacterial agent (2) . Effect on the respiratory and cardiovascular systems, autonomic nervous system and other functions}; Furuhata K et al.; General pharmacological effects of T-3761, a new oral quinolone antibacterial agent, on the respiratory and cardiovascular systems, autonomic nervous system and other functions were investigated in laboratory animals . The results obtained are summarized as follows . 1 . Respiratory and cardiovascular systems: Oral administration of T-3761 at doses of 100-1,000 mg/kg did not affect in conscious rats . But intravenous administration of T-3761 at doses of 10-100 mg/kg caused an increase in respiratory rate, induced hypotension, caused increase or decrease in heart rate and altered ECG patterns (elevation of T waves and reduction of voltage of QRS complexes, etc.) in anesthetized dogs . Intravenous administration of T-3761 at doses of 10-100 mg/kg showed respiratory rate increase or decrease, hypertension, heart rate decrease and ECG patterns changes (T waves elevation and extrasystole) in anesthetized rabbits . 2 . Autonomic nervous system and smooth muscle organs: T-3761 increased the epinephrine-induced contraction of the isolated guinea pig vas deferens at concentration of 10(-5)-10(-4) g/ml . T-3761 decreased the acetylcholine-induced contraction of the isolated guinea pig ileum and epinephrine-induced relaxation of the isolated guinea pig trachea-chain at concentration of 10(-4) g/ml . T-3761 increased the norepinephrine-induced contraction of the isolated rabbit thoracic aorta at concentration of 10(-4) g/ml . Oral administration of T-3761 at a dose of 1,000 mg/kg exerted slight mydriasis in mice . 3 . Digestive system: T-3761 decreased the spontaneous motilities of isolated ileum and colon at concentration of 10(-4) g/ml . Oral administration of T-3761 at a dose of 1,000 mg/kg inhibited gastric output and intestinal transit time in rats or mice . 4 . Renal functions: Oral administration of T-3761 at a dose of 300 mg/kg increased Na+ excretion but did not affect PSP excretion in rats . 5 . Hematological examinations: T-3761 showed no effects on resistance to hemolysis, blood coagulation and platelet aggregation in rabbits at concentration of 10(-6)-10(-4) g/ml . Oral administration of T-3761 at dose of 100-1,000 mg/kg did not affect bleeding time or blood glucose level in rats . 6 . Miscellaneous effects: Intravenous administration of T-3761 at a dose of 100 mg/kg slightly inhibited the twitch tension of gastrocnemius in anesthetized rats . Oral administration of T-3761 at doses of 300-1,000 mg/kg exerted slight augmentation of carrageenin-induced hind paw edema in rats . From these results, it can be assumed that T-3761 had a wide safety margin as an oral antibacterial agent. Jpn J Antibiot, 1995 May, 48(5), 692 - 705 {General pharmacology of T-3761, a new oral quinolone antibacterial agent (1) . Effect on the central nervous system}; Furuhata K et al.; General pharmacological effects of T-3761, a new oral quinolone antibacterial agent, on the central nervous system were investigated in laboratory animals . The results obtained are summarized as follows . 1 . T-3761 exerted no significant effects on spontaneous motor activity, motor coordination, pentobarbital-induced hypnosis, electroshock-, pentetrazole- or strychnine-induced convulsion, acetic acid-induced writhing responses, reserpine-induced hypothermia and ptosis in mice at oral doses of 100, 300 and 1,000 mg/kg . The same oral doses of T-3761 exerted no significant effects on body temperature and passive avoidance response in rats . 2 . T-3761 had no effects on EEG in cats and spinal reflex in rats at intravenous doses of 10, 30 and 100 mg/kg . 3 . Convulsions were not observed in mice after any oral combinations of T-3761 at a dose of 200 or 1,000 mg/kg with 14 different nonsteroidal anti-inflammatory drugs (NSAIDs) including fenbufen . 4 . An oral combination of T-3761 even at a higher doses of 3,000 mg/kg with 4-biphenylacetic acid (BPAA) which is a principally active metabolite of fenbufen also did not induce convulsions in mice . 5 . T-3761 did not inhibit GABA receptor binding in rat brain synaptic membranes at 10(-4) M in either the absence or presence of BPAA . These results suggest that T-3761 is an antibacterial agent which would be unlikely to produce any side effects on the central nervous system and to produce convulsion when combined with NSAIDs in clinical use. Eur J Vasc Endovasc Surg, 1995 May, 9(4), 408 - 14 An infection-resistant PTFE vascular graft; spiral coiling of the graft with ofloxacin-bonded PTFE thread; Okahara K et al.; OBJECTIVE: To develop an infection-resistant polytetrafluoroethylene (PTFE) vascular graft for potential clinical use in grafting in sites of bacterial contamination and in replacement of the infected grafts . SETTING: Experimental study in rabbits . MATERIALS AND METHODS: An antibiotic ofloxacin (OFLX) was bonded to a sheet of PTFE by impregnation, which was cut and twisted into fine threads . The in-vitro antibacterial activity of OFLX-PTFE thread was determined by measuring the zone of growth inhibition against Escherichia coli . The thread was spirally coiled around a ridged outerwall PTFE to make the OFLX-PTFE graft . OFLX-PTFE graft or control graft was interposed in the inferior vena cava (IVC) of rabbits and the entire graft was covered with fibrin containing a fixed number of E . coli . Three or 7 days after the grafting, the grafts with perigraft tissue were harvested and subjected to bacteriological studies . RESULTS: In spite of early phase rapid elution of OFLX, a significant antibacterial activity was retained for more than 2 weeks . The antibacterial activity of OFLX-PTFE threads implanted in the subcutaneous space of rabbits decreased to 48% after 24 h and to approximately 1% after a week . The swab culture of all the control grafts was positive, while only one of 13 PTFE-OFLX grafts was positive . The number of viable bacteria in the perigraft tissue of OFLX-PTFE grafts was remarkably low in comparison with that of control grafts . Thus, the OFLX-PTFE grafts exhibited a marked in-vivo antibacterial activity . CONCLUSION: By a unique method, it was possible to furnish PTFE graft with an excellent infection-resistant property, without affecting the original biological behaviour. Urol Nefrol (Mosk), 1995 May-Jun, (3), 31 - 2 {Lomefloxacin in the treatment and prevention of urogenital infection}; Perepanova TS et al.; A new antibiotic from fluoroquinolone series maxaquine (lomefloxacin) made in USA (Searle {correction of Surl}) has been tried in the treatment of urogenital infection (chronic cystitis, prostatitis, pyelonephritis, acute epididymitis, chlamydial urethroprostatitis) as well as to warrant antibacterial preparation before extracorporeal lithotripsy . The duration of the treatment course (3-28 days) was oriented to nosological form . The 24-h dose ranged from 400 to 800 mg . Side effects manifested with dyspepsia in 4 patients, worsening of memory in 2 patients . Photosensitization did not occur . Maxaquine clinical efficacy is similar to aminoglycosides and is superior to cephalosporins of the third generation . As for fluoroquinolone antibiotics, maxaquine can be compared to cyprofloxacine . The drug proved effective against urethroprostatitis and urethrocystitis of chlamydial origin . The responses to maxaquine favour its application in hospitals as second-line drug, whereas outpatiently it can be used for short-term empiric therapy. Yakugaku Zasshi, 1995 May, 115(5), 394 - 9 {The uptake of nalidixic acid and enoxacin by rat renal cortical slices in rat}; Oda M et al.; The mechanisms involved in the renal excretion of quinolone and new quinolone antibacterial drugs are still incompletely understood . The purpose of this study was to examine the renal handling of nalidixic acid (NA) and enoxacin (ENX), using the renal cortical slices uptake techniques in rats . It was demonstrated that both NA and ENX were taken against a concentration gradient by a saturable processes resulting from the ratio of slice to medium (ratio of S/M) being dependent on the time and the concentration . It was indicated that the inhibition of uptake by 2,4-dinitrophenol, ouabain and sodium cyanate was shown to be an energy dependence . Probenecid and cimetidine exhibited that they might inhibit NA uptake slightly . ENX uptake was inhibited by probenecid, cimetidine, guanidine and disopyramide, suggesting that ENX might possess an affinity for both anionic and cationic transport mechanisms. Diagn Microbiol Infect Dis, 1995 May-Jun, 22(1-2), 5 - 12 Cefotaxime . Unchanged antibacterial activity over years? Wiedemann B, Dietz H. During recent years new mechanisms of beta-lactam resistance have developed with the genetic origin on the chromosome or plasmids . Nevertheless, most multicenter studies can demonstrate that cefotaxime has retained its antibacterial activity toward the relevant species . However, it is important to follow the development of resistance closely in hospitals, where epidemic outbreaks of bacterial strains with extended-spectrum beta-lactamases can create difficulties in the treatment of infectious diseases. Drugs, 1995 May, 49(5), 767 - 93 Lenograstim . A review of its pharmacological properties and therapeutic efficacy in neutropenia and related clinical settings; Frampton JE et al.; Lenograstim is a recombinant glycosylated human granulocyte colony-stimulating factor (rHuG-CSF) which principally regulates the formation and function of neutrophils . Like other colony-stimulating factors (CSFs), lenograstim has been developed for the prevention and treatment of iatrogenic and disease-related neutropenic conditions . In phase III clinical studies, prophylactic administration of lenograstim shortened the duration of chemotherapy-induced neutropenia in patients with nonmyelogenous cancers who received standard-dose chemotherapy or myeloablative regimens followed by bone marrow transplantation (BMT) . A decrease in the incidence of infection after standard regimens and fewer days with infectious and febrile neutropenic episodes during recovery from BMT occurred concomitantly with the amelioration of neutropenia . In each setting, the decrease in morbidity was associated with shorter hospitalisation times and reduced administration of parenteral antibacterial agents . As with another rHuG-CSF, filgrastim, bone pain (non-serious) was the most common adverse reaction to lenograstim therapy . This occurred in 13% of lenograstim recipients and 5% of placebo recipients treated for chemotherapy-induced neutropenia with standard regimens . Lenograstim may facilitate dose optimisation and permit limited dose intensification of standard chemotherapy . Furthermore, the drug, used alone or in combination with chemotherapy, is effective in mobilising peripheral blood progenitor cells (PBPCs) for subsequent reinfusion . The latter is a promising technique which may supplement or ultimately replace BMT for stem cell rescue after myeloablative chemotherapy . However, it has yet to be established whether the dose intensification achievable with lenograstim and/or stem cell rescue has a material effect on relapse-free and survival times . Preliminary data suggest that lenograstim is effective in increasing the neutrophil count in patients with severe chronic neutropenia (Kostmann's syndrome), as well as patients with AIDS or AIDS-related complex with zidovudine-induced neutropenia . Thus, lenograstim, like other CSFs, is a valuable adjunct to cytotoxic chemotherapy for the treatment of nonmyelogenous cancers, including myeloablative regimens followed by stem cell rescue with BMT and/or PBPC infusion . Future clinical experience is likely to confirm the usefulness of the drug in the management of disease-related neutropenia, myeloid disorders and neutropenia in patients with AIDS. Gene, 1995 Apr 24, 156(2), 247 - 51 FKBP39, a Drosophila member of a family of proteins that bind the immunosuppressive drug FK506; Theopold U et al.; A cDNA, coding for the first Drosophila melanogaster homolog of a family of proteins (FK506-binding proteins, FKBPs) which bind to the immunosuppressive drug FK506, was isolated . The deduced aa sequence corresponds to a 39-kDa product (FKBP39) which, besides a domain with similarity to FKBPs, has a highly charged domain with two strongly acidic stretches . The transcript could be detected in all developmental stages, with the highest expression in the embryo . In adult flies, the strongest signal was detected in the ovaries . Although the FKBP39 gene is expressed in the immunocompetent D . melanogaster blood cell line, mbn-2, the antibacterial defense reaction of these cells is unaffected by FK506. Biochem J, 1995 Apr 15, 307 ( Pt 2), 361 - 7 Stimulation of NADH-dependent microsomal DNA strand cleavage by rifamycin SV; Kukielka E et al.; Rifamycin SV is an antibiotic anti-bacterial agent used in the treatment of tuberculosis . This drug can autoxidize, especially in the presence of metals, and generate reactive oxygen species . A previous study indicated that rifamycin SV can increase NADH-dependent microsomal production of reactive oxygen species . The current study evaluated the ability of rifamycin SV to interact with iron and increase microsomal production of hydroxyl radical, as detected by conversion of supercoiled plasmid DNA into the relaxed open circular state . The plasmid used was pBluescript II KS(-), and the forms of DNA were separated by agarose-gel electrophoresis . Incubation of rat liver microsomes with plasmid plus NADH plus ferric-ATP caused DNA strand cleavage . The addition of rifamycin SV produced a time- and concentration-dependent increase in DNA-strand cleavage . No stimulation by rifamycin SV occurred in the absence of microsomes, NADH or ferric-ATP . Stimulation occurred with other ferric complexes besides ferric-ATP, e.g . ferric-histidine, ferric-citrate, ferric-EDTA, and ferric-(NH4)2SO4 . Rifamycin SV did not significantly increase the high rates of DNA strand cleavage found with NADPH as the microsomal reductant . The stimulation of NADH-dependent microsomal DNA strand cleavage was completely blocked by catalase, superoxide dismutase, GSH and a variety of hydroxyl-radical-scavenging agents, but not by anti-oxidants that prevent microsomal lipid peroxidation . Redox cycling agents, such as menadione and paraquat, in contrast with rifamycin SV, stimulated the NADPH-dependent reaction; menadione and rifamycin SV were superior to paraquat in stimulating the NADH-dependent reaction . These results indicate that rifamycin SV can, in the presence of an iron catalyst, increase microsomal production of reactive oxygen species which can cause DNA-strand cleavage . In contrast with other redox cycling agents, the stimulation by rifamycin SV is more pronounced with NADH than with NADPH as the microsomal reductant . Interactions between rifamycin SV, iron and NADH generating hydroxyl-radical-like species may play a role in some of the hepatotoxic effects associated with the use of this antibacterial antibiotic. Biochim Biophys Acta, 1995 Apr 13, 1243(3), 295 - 9 Effect of a chemical or proteolytic modification on the biological activity of guinea-pig cationic peptide; Yamashita T et al.; Guinea-pig neutrophil cationic peptides (GNCPs) are single polypeptides containing 31 amino acid residues and three intramolecular disulfide bonds, which show both antibacterial and histamine-releasing activities . Reduction and alkylation of the disulfide bonds of GNCP did not reduce both biological activities . When pyridylethylated GNCP was digested with trypsin, the biological activities were almost lost, whereas the chymotryptic digest retained the biological activities . Chymotrypsin digested fragments were purified by RP-HPLC, and three active peptide fragments containing two Arg residues at the N-terminal sequence were isolated . When the biological activities were examined using synthetic peptides containing various numbers of Arg residue at the N-terminus, the omission of the Arg residues was found to reduce remarkably the antibacterial and histamine-releasing activities . Together these observations indicate that the primary structures containing Arg residues at the N-terminus but not the intramolecular disulfide cross-linking are important for the expression of the biological activities of GNCP. Proc Natl Acad Sci U S A, 1995 Apr 11, 92(8), 3449 - 53 Retro and retroenantio analogs of cecropin-melittin hybrids; Merrifield RB et al.; Hybrid analogs of cecropin A (CA) and melittin (M), which are potent antibacterial peptides, have been synthesized . To understand the structural requirements for this antibacterial activity, we have also synthesized the enantio, retro, and retroenantio isomers of two of the hybrids and their N-terminally acetylated derivatives . All analogs of CA(1-13)M(1-13)-NH2 were as active as the parent peptide against five test bacterial strains, but one bacterial strain was resistant to the retro and retroenantio derivatives . Similarly, all analogs of CA(1-7)M(2-9)-NH2 were active against four strains, while two strains were resistant to the retro and retroenantio analogs containing free NH3+ end groups, but acetylation restored activity against one of them . From these data it was concluded that chirality of the peptide was not a critical feature, and full activity could be achieved with peptides containing either all L- or all D-amino acids in their respective right-handed or left-handed helical conformations . For most of the bacterial strains, the sequence of these peptides or the direction of the peptide bonds could be critical but not both at the same time . For some strains, both needed to be conserved. Nucleic Acids Res, 1995 Apr 11, 23(7), 1140 - 5 Drosophila immunity . A sequence homologous to mammalian interferon consensus response element enhances the activity of the diptericin promoter; Georgel P et al.; Bacterial challenge of larvae or adults of Drosophila induces the rapid transcription of several genes encoding antibacterial peptides with a large spectrum of activity . One of these peptides, the 82-residue anti-gram negative diptericin, is encoded by a single intronless gene and we are investigating the control of expression of this gene . Previous studies using both transgenic experiments and footprint analysis have highlighted the role in the induction of this gene of a 30 nucleotide region which contains three partially overlapping motifs with sequence homology to mammalian NF-kappa B and NF-IL6 response elements and to the GAAANN sequence present in the interferon consensus response elements of some mammalian interferon-induced genes . We now show that the latter sequence binds in immune responsive tissues (fat body, blood cells) of Drosophila a approximately 45 kDa polypeptide which cross-reacts with a polyserum directed against mammalian interferon Regulatory Factor-I . Using a transfection assay of Drosophila tumorous blood cells, we show that the GAAANN sequence positively regulates the activity of the diptericin promoter . We propose that this motif cooperatively interacts with the other response elements in the regulation of the diptericin gene expression. Schweiz Med Wochenschr, 1995 Apr 8, 125(14), 676 - 83 {Frequency of antibiotics-associated colitis in hospitalized patients in 1974-1991 in "Comprehensive Hospital Drug Monitoring", Bern/St . Gallen}; Zehnder D et al.; In 3 divisions of internal medicine of teaching hospitals of the Comprehensive Hospital Drug Monitoring (CHDM) Foundation Bern/St Gallen, 42,920 patients consecutively admitted between 1974-1991 were investigated for adverse drug reactions . Of these 16,150 patients (38%) had received at least one systemically administered antibacterial drug during the hospital stay . Antibiotic-associated colitis included the following diagnoses: pseudomembranous colitis, hemorrhagic colitis and milder forms of colitis . We collected the data of these patients by searching for all diagnoses which might represent antibiotic-associated colitis (from the list of WHO adverse drug reaction terminology) . 9 individual patients with one episode of probable antibiotic-associated colitis were found . In 5 of these cases, only one drug given during the hospital stay seemed to be implicated . An additional 32 patients were admitted with antibiotic-associated colitis in relation to treatment with the same groups of drugs before hospital admission . Based on the exposure pattern of the 9 patients with antibiotic-associated colitis compared to all patients exposed during hospital stay, we estimated the following frequencies related to the drug groups with at least 1,000 patients exposed: for all antibacterial chemotherapeutics 0.6/1000 (0.25-1.06); all penicillins 0.6/1000 (0.22-1.32), for benzyl-, phenoxy-, ureido-, isoxazolyl penicillins and methicillin 2.0/1000 (0.42-5.92) and aminopenicillin or analogues, with or without clavulanic acid 0.6/1000 (0.18-1.35) . For cephalosporins the frequency is 1.4/1000 (0.17-5.12) . Under sulfonamides combined with trimethoprim or related substances (5077 exposed patients) and fluoroquinolones (1043 exposed patients) no case was observed.(ABSTRACT TRUNCATED AT 250 WORDS) Microb Drug Resist, 1995 Spring, 1(1), 43 - 8 New prospects for antibacterial agents against multidrug-resistant pneumococci; Appelbaum PC; Since the first description of penicillin-resistant pneumococci nearly 30 years ago, drug-resistance has become widespread throughout the world . This review focuses upon the in vitro susceptibility of penicillin-susceptible and -resistant pneumococci to new and existing agents. Pulm Pharmacol, 1995 Apr-Jun, 8(2-3), 65 - 81 New concepts in the pulmonary disposition of antibiotics; Bergogne-Berezin E; Despite interpretive problems associated with studies of antibiotic concentrations in tissues, it is of major interest to correlate the presence of the drug at significant concentrations in lung tissues and fluids at a particular site with its clinical efficacy . All the models described above have their uses as well as their limitations . Measurement of antibiotic concentrations achieved in lung parenchyma, ELF, bronchial mucosa of bronchial secretions has shown variable levels for the same drug . Many respiratory infections are caused by obligate or facultative intracellular pathogens, which may be eradicated as a result of intracellular penetration and accumulation of quinolones, of macrolides, as shown in several models of phagocytic cells, and as a result of intracellular antibacterial activities . For bacterial infections located in extracellular pulmonary sites, a knowledge of achievable concentrations of beta-lactams, of aminoglycosides, of quinolones should be of value, whereas for bacteria multiplying in alveolar macrophages the high concentrations of the new macrolides or new fluoroquinolones that can be achieved in extravascular and intracellular fluids should have clinical relevance . Animal models of severe pneumonia, as well as studies in patients hospitalized in intensive care units, have provided correlation between clinical outcomes and high lung tissue and intramacrophagic concentrations of fluoroquinolones, or of macrolides in legionellosis, or of ceftazidime or imipenem in pseudomonal pneumonia. Infect Immun, 1995 Apr, 63(4), 1387 - 90 Endogenous interleukin-12 is involved in resistance to Brucella abortus infection; Zhan Y et al.; Protective immunity against Brucella abortus is mediated by acquired cellular resistance, with gamma interferon (IFN-gamma)-producing T cells playing a key role . Interleukin-12 (IL-12) is a cytokine that has a profound effect on the induction of IFN-gamma-producing Th1 and NK cells . Here we report that depletion of endogenous IL-12 before infection of mice significantly exacerbated brucella infection . IL-12-depleted mice also had reduced splenomegaly resulting from infection and showed a decrease in percentage and absolute numbers of macrophages compared with those in control infected mice . Furthermore, spleen cells from IL-12-depleted mice had a reduced ability to produce nitrite, a product of activated macrophages . This could be the result of the low production of IFN-gamma by splenic T cells observed in the IL-12-depleted mice . The mechanism whereby IL-12 controls antibacterial resistance is discussed. Insect Biochem Mol Biol, 1995 Apr, 25(4), 511 - 8 Identification of early genes in the Drosophila immune response by PCR-based differential display: the Attacin A gene and the evolution of attacin-like proteins; Asling B et al.; We are using the PCR-based differential display technique to isolate genes which are induced during the immune response in Drosophila . In this way, a cDNA clone for a member of the attacin family of antibacterial proteins was isolated . The corresponding Attacin A (Att A) gene is localized at 51A-B on the second chromosome, and it is closely linked to at least one more cross-hybridizing gene . Injection of bacteria induces a 0.8 kb transcript, with expression kinetics similar to that of cecropin . Drosophila attacin is most closely related to sarcotoxin II of Sarcophaga peregrina, but it lacks the extra domains that are unique to this protein, and the overall domain structure of the Att A gene product is identical to that of the attacins from Hyalophora cecropia. J Chemother, 1995 Apr, 7(2), 126 - 32 Complexes of ciprofloxacin with metal ions contained in antacid drugs; Teixeira MH et al.; Simultaneous administration of antacids containing magnesium or aluminium and ciprofloxacin or other quinolones decreases the gastrointestinal absorption of those antibacterial agents . Current speculation about the mechanism of this interaction has focused on drug-cation chelation . The present study was designed to detect the protonation in solutions and the formation of the complex species at the pH levels typical of the gastrointestinal tract . It involves the study of ciprofloxacin in aqueous solutions containing Al3+ and (or) Mg2+ by combining the results of potentiometric and spectroscopic (1H nuclear magnetic resonance) techniques . Calculations were only performed for data in the range 4.5 < pH < 5.5 (pH levels typical of gastrointestinal tract) and the results of both methods are made self-consistent, assuming an equilibrium model including complex species MHL, MLOH (where H2L denotes ciprofloxacin and M is Al3+ or Mg2+); their formation constants are given. Aust Vet J, 1995 Apr, 72(4), 139 - 41 The use of toltrazuril for the prevention of coccidiosis in piglets before weaning; Driesen SJ et al.; To determine the efficacy of toltrazuril as a prophylactic treatment for coccidiosis in piglets caused by Isospora suis (I suis), a single 1.0 mL dose of toltrazuril was administered orally to 1056 piglets between 3 and 6 days of age, in 5 piggeries . Prophylactic treatment of piglets reduced the occurrence of coccidiosis in litters from 71% to 22% . The number of antibacterial treatments given and the number of piglets affected per litter were also significantly reduced, resulting in some improvement in growth rates to weaning . The severity of diarrhoea was significantly reduced, as was the amount of oocyst excretion . The number of days that piglets excreted oocysts in the faeces was reduced from 4.9 days to 2.5 days . The detection of I suis in piglets with diarrhoea was reduced from 84% in the untreated piglets to 6% in the piglets given the prophylactic treatment. J Biomol Struct Dyn, 1995 Apr, 12(5), 993 - 1008 Two-dimensional 1H NMR study of a tetradecapeptide with the consensus sequence Arg5-Asp-Val-Arg-Gly9: structural effects of the outside substitution Ser12 by Ala12; Riand J et al.; Conformation of a tetradecapeptide with a RXVRG consensus sequence, Arg5-Asp-Val-Arg-Gly9, found in several precursors of antibacterian peptides, was investigated in dimethylsulfoxide solution by proton NMR spectroscopy . Complete resonance assignments and conformational parameters were obtained through correlated (COSY) and nuclear Overhauser (NOESY) techniques . The 3J(alpha H, beta H) coupling constants and the intramolecular NOE, NH...beta H, were used to analyse the conformers around the C alpha-C beta bond and, in four cases, to obtain stereospecific assignments . Use of restraints derived from NOE connectivities and 3J(NH, alpha H) coupling constants allows the determination of a range of phi and psi dihedral angles for all the residues in the sequence . The present NMR results provide favourable evidence for the formation of two bends in the consensus sequence of the tetradecapeptide . The first one has most of the features of a Glu4-Val7 beta-turn (low temperature coefficient of the Val7NH chemical shift, Arg5 alpha H...Val7NH and Asp6NH...Val7NH NOE correlations) . The second one exhibits only the Asp6 alpha H...Arg7NH and Val7NH...Arg8NH NOE interactions . These consensus sequence organizations proposed were confirmed by molecular modeling based on low potential energy structure on the {4-9} fragment with high agreement of NOE data . Overall, the substitution of Ser12 by Ala12 shifts the conformation of the hydrophobic moiety {10-14} towards a quite random coil structure in this fragment and strongly destabilizes the folded structures of the consensus domain where only one NH (Val7) is solvent-shielded opposed to three (Asp6 to Arg8) in the {Ser12} tetradecapeptide . These conformational changes could be related to the processing enzyme activities on these model oligopeptides. Arch Pharm (Weinheim), 1995 Apr, 328(4), 325 - 8 Synthesis and biological investigations of some new thiazolylbenzimidazoles and benzimidazolylthiazolo{3,2-a}pyridines; Rida SM et al.; 2-{(4-Oxo-4,5-dihydrothiazol-2-yl)methyl}-1H-benzimidazole (2) was prepared through the reaction of 2-cyanomethyl-1H-benzimidazole (1) with thioglycolic acid . The syntheses of its arylidene 3 and diazo-coupled compounds 5 and the cyclization of the aforementioned thiazolylbenzimidazole to benzimidazolylthiazolo{3,2-a}pyridines 8 were also performed . The prepared compounds were screened for their in-vitro antibacterial, antifungal, anti-HIV, and anticancer activities: they show promising antifungal activity. J Otolaryngol, 1995 Apr, 24(2), 134 - 7 Cefuroxime: pharmacokinetics in cochlear perilymph, cerebrospinal fluid, and plasma; Sun AH et al.; Very little is known about the permeability of contemporary antibiotics through the blood:perilymph barrier . In this study, we measure the concentration of cefuroxime in perilymph, cerebrospinal fluid (CSF), and plasma in the guinea pig following intravenous administration by using the technique of high-performance liquid chromatography . The results of our study demonstrate a higher permeability of cefuroxime in perilymph than in CSF with a similar concentration profile over time in both fluids . This suggests that each of the two fluid compartments has its own drug barrier, with little or no free passage from CSF to perilymph . On the basis of these experimental findings, we feel that cefuroxime has considerable potential as an antibacterial agent for the treatment or prevention of bacterial labyrinthitis. Chem Pharm Bull (Tokyo), 1995 Apr, 43(4), 603 - 6 Correlation between the adsorption tendency of cationic disinfectant onto a synthetic multibilayer and its minimum inhibitory concentration; Makino M et al.; Minimum inhibitory concentration (the lowest concentration able to inhibit growth of microorganisms after 48 h contract) could be useful as a measure of bactericidal activity of cationic disinfectants . The relation between the minimum inhibitory concentration (microgram/ml) of cationic disinfectants against gram-negative microorganisms and the adsorption tendency of these compounds onto a lipid bilayer was therefore studied using a quartz crystal microbalance (QCM) coated with synthetic multibilayer film . The adsorbed amounts of these compounds were obtained from the frequency decrease of the QCM in aqueous solutions . The calculated partition coefficients showed a good correlation with the minimum inhibitory concentrations of cationic disinfectants against E . coli and K . pneumoniae, supporting the validity of this method for predicting minimum inhibitory concentration . The results suggest that effective antibacterial agents are only slightly absorbed, and may mostly penetrate through the lipid bilayer. Jpn J Antibiot, 1995 Apr, 48(4), 514 - 21 {A combined consecutive therapy with fosfomycin and sulbactam/cefoperazone for bacterial infections associated with hematological diseases}; Misawa S et al.; A combination antibacterial therapy with fosfomycin (FOM) and sulbactam/cefoperazone (SBT/CPZ) was applied to 78 patients with severe infections associated with hematological diseases . In this protocol, FOM was followed by SBT/CPZ and each drug was administered for 1 hour intravenously and consecutively . Among 72 evaluable patients, 43 patients had acute leukemia, myeloblastic or lymphoblastic, 22 had malignant lymphoma, 3 had multiple myeloma, and 4 had other hematological diseases as underlying diseases . Bacterial infections diagnosed were sepsis in 21 patients, suspected sepsis in 47, and other infections in 4 . The overall efficacy rate of this treatment was 72.2%, and those for individual infections were 66.7% for sepsis, 74.5% for suspected sepsis, and 75.0% for other infectious diseases . Among 22 bacteria separated from patients with sepsis, 78.6% (11/14 strains) were eradicated by this treatment . This protocol was also effective in 57.1% (8/14) of patients whose granulocyte count was less than 100/mm3 during the course of treatment as well as in 83.3% (15/18) of patients with granulocyte count over 500/mm3 . There was no difference in effectiveness between those patients to whom G-CSF was administered and those to whom it was not (17/24, 70.8% vs 35/48, 72.9%) . As an adverse reaction, a transient increase of GOT and/or GPT was observed in 2 patients (2.8%) . The consecutive administration treatment of FOM and SBT/CPZ is thus an effective and safe regimen for the treatment of patients with hematological diseases complicated by severe infections. J Vet Med Sci, 1995 Apr, 57(2), 363 - 4 In vitro antibacterial activity of florfenicol against Actinobacillus pleuropneumoniae; Ueda Y et al.; A total of 90 strains of Actinobacillus pleuropneumoniae isolated from porcine pneumonic lungs in Japan during 1989 to 1993 were investigated for their in vitro susceptibility to florfenicol (a derivative of thiamphenicol) and other drugs . The minimal inhibitory concentrations of florfenicol against A . pleuropneumoniae ranged from 0.2 to 1.56 micrograms/ml with a peak at 0.39 microgram/ml . Florfenicol showed a high antibacterial activity against A . pleuropneumoniae regardless of the sensitivity of the strains to thiamphenicol. J Med Chem, 1995 Mar 31, 38(7), 1203 - 15 7-Azetidinylquinolones as antibacterial agents . 3 . Synthesis, properties and structure-activity relationships of the stereoisomers containing a 7-(3-amino-2-methyl-1-azetidinyl) moiety; Frigola J et al.; A series of stereochemically pure 7-(3-amino-2-methyl-1-azetidinyl)-1,4- dihydro-6-fluoro-4-oxoquinoline- and -1,8-naphthyridine-3-carboxylic acids, with varied substituents at the 1-, 5-, and 8-positions, was prepared to determine the effects of chirality on potency and in vivo efficacy relative to the racemic mixtures (for part 2, see: J . Med . Chem . 1994, 37, 4195-4210) . A series of chiral 9-fluoro-2,3-dihydro-3-methyl-7-oxo-10-(substituted-1- azetidinyl)-7H-pyrido{1,2,3- de}-1,4-benzoxazine-6-carboxylic acids was synthesized to study the effect of the azetidine moiety on tricyclic quinolone antibacterial agents . A series of amino acid prodrugs of chiral naphthyridines 24a and 24b and quinolone 33a (cetefloxacin) was prepared and evaluated for antibacterial activity, solubility, and pharmacokinetic behavior . The absolute configuration of the new azetidinylquinolones was established by X-ray analysis of one of the diastereomeric salts of the resolved azetidinols (15) and of compound 25a (E-4767), which showed the best in vitro and in vivo overall profile . Structure-activity relationship studies indicated that the absolute stereochemistry at the asymmetric centers of both the azetidine and the oxazine rings was critical to increase in vitro activity and oral efficacy . The 3S configuration in the pyridobenzoxazine series and the (2S,3R) configuration of the 3-amino-2-methylazetidine moiety for all new compounds conferred the best antibacterial activity. J Biol Chem, 1995 Mar 17, 270(11), 6199 - 204 cDNA sequence and expression of the ceratotoxin gene encoding an antibacterial sex-specific peptide from the medfly Ceratitis capitata (diptera); Marchini D et al.; Ceratotoxins are antibacterial 3-kDa molecular mass amphiphilic peptides isolated from the female reproductive accessory glands of the medfly Ceratitis capitata . They are physiologically related to bee melittin and show amino acid sequence homology with magainin peptides . In this paper, we report the complete sequence of cDNA coding for ceratotoxin A and the expression of the gene during the life cycle of the insect . Experimental data show that the ceratotoxin is a gene expressed exclusively in the imaginal stages and that it is female-specific, related to sexual maturity, and stimulated by mating . Differently from most antibacterial insect hemolymph peptides, it is not induced by microbial infection . Western blot analysis using an anti-ceratotoxin antibody indicates the female accessory glands as the only site where the production of the ceratotoxin peptide occurs. Mol Gen Genet, 1995 Mar 10, 246(5), 628 - 37 Resistance to trifluoroperazine, a calmodulin inhibitor, maps to the fabD locus in Escherichia coli; Bouquin N et al.; A mutant, tfpA1, resistant to the calmodulin inhibitor trifluoroperazine (TFP) at 30 degrees C, was isolated in Escherichia coli . The mutant showed a reduced growth rate at 30 degrees C and was temperature sensitive (ts) at 42 degrees C for growth, forming short filaments . The mutation was mapped to the 24 min region of the chromosome and the gene was cloned by complementation of the ts defect . Subsequent subcloning, complementation analysis, marker rescue mapping and sequencing, identified tfpA as fabD, encoding the 35 kDa, malonyl-coenzyme A transacylase (MCT) enzyme, required for the initial step in the elongation cycle for fatty acid biosynthesis . Resistance to TFP may result from altered permeability of the cell envelope, although the mutant remained sensitive to other calmodulin inhibitors and to other antibacterial agents . Alternatively, resistance may be more indirect, resulting from alterations in intracellular Ca++ levels which affect the activity of the TFP target in some way. Pharmacoeconomics, 1995 Apr, 7(4), 347 - 56 The cost effectiveness of amoxicillin/clavulanic acid as antibacterial prophylaxis in abdominal and gynaecological surgery; Davey PG et al.; The objective of this study was to compare the cost effectiveness of amoxicillin/clavulanic acid with other antibacterial regimens for prophylaxis of infection after elective abdominal or gynaecological surgery . Data from 21 previously published comparative clinical trials were used to calculate statistical confidence intervals for differences in postoperative wound infection rate . A simple model was used to produce a tabular sensitivity analysis of cost effectiveness over a wide range of costs of wound infection and potential differences in efficacy . For more expensive comparator regimens, including combination regimens utilising gentamicin and metronidazole, amoxicillin/clavulanic acid was either likely to be more cost effective or equally cost effective . For example, in trials of colonic surgery the comparators were on average 11.39 pounds more expensive than amoxicillin/clavulanic acid, which was > 95% likely to be more cost effective unless the cost of wound infection was estimated to be > 1519 pounds . Amoxicillin/clavulanic acid was more expensive than only 2 of the 21 comparators . Furthermore, in one of these 2 trials it was also significantly more effective than the comparator . In this trial, amoxicillin/clavulanic acid was > 95% likely to be more cost effective as prophylaxis in hysterectomy than rectal metronidazole, provided that the cost of wound infection was estimated to be > 179 pounds . In conclusion, this analysis shows that amoxicillin/clavulanic acid, given as monotherapy, is likely to be equally or more cost effective than a wide range of comparator regimens for prophylaxis of elective abdominal or gynaecological surgery. Antimicrob Agents Chemother, 1995 Mar, 39(3), 613 - 9 Mechanism of tonB-dependent transport of KP-736, a 1,5-dihydroxy-4-pyridone-substituted cephalosporin, into Escherichia coli K-12 cells; Tatsumi Y et al.; The mechanism of transport of KP-736, a novel cephalosporin with a 1,5-dihydroxy-4-pyridone moiety at the C-7 position, into the Escherichia coli K-12 cell was investigated by determining the susceptibilities of iron transport mutants to KP-736 . The tonB mutant showed a higher degree of resistance to KP-736, indicating that KP-736 was incorporated into E . coli cells via the tonB-dependent iron transport system . The product of the exbB gene was also necessary for the maximal antibacterial potency of KP-736 . Cir-lacking and Fiu-lacking mutants showed a moderate level of resistance to KP-736 . However, mutants lacking any one of the proteins FepA, FecA, FhuA, and FhuE did not show any increased resistance to KP-736 . Two types of spontaneous mutants (e.g., KT1004 and KT1011) could be isolated from cir and fiu mutants by selection for KP-736 resistance and showed the same level of resistance to KP-736 as a tonB mutant . KT1004 showed tonB phenotypes, resistance to phage phi 80, and loss of FecA, whereas KT1011 did not . KT1011 lost the ability to express both Cir and Fiu proteins . These results indicate that the Cir and Fiu outer membrane proteins are involved specifically in the tonB-dependent transport process of KP-736 . Against OmpF- and OmpC-deficient transformants producing various groups of beta-lactamases, KP-736 was more effective than the other cephalosporins tested. J Small Anim Pract, 1995 Mar, 36(3), 119 - 23 Canine eosinophilic folliculitis and furunculosis in three cases; Curtis CF et al.; The historical, clinical and histopathological features of three dogs with eosinophilic folliculitis and furunculosis are described . The disease was characterised by the rapid development of pruritic, papular, pustular and ulcerative lesions on the dorsum of the muzzle . Skin lesions were confined to the face in two cases . The third dog had more generalised pustular lesions . Skin biopsy specimens showed marked eosinophil infiltration particularly centred on pilosebaceous units . Dermal collagen necrosis was evident in two cases . Similar facial lesions have previously been described as 'nasal pyoderma' . The three dogs failed to respond to initial antibacterial therapy but showed a rapid clinical response when prednisolone was given orally at doses ranging from 1 to 2.2 mg/kg, in addition to the antibacterial therapy, suggesting that glucocorticoids are indicated for the treatment of eosinophilic folliculitis and furunculosis . The aetiology of the disease was not determined. Insect Biochem Mol Biol, 1995 Mar, 25(3), 385 - 92 Characterization of a Bombyx mori cDNA encoding a novel member of the attacin family of insect antibacterial proteins; Sugiyama M et al.; A Bombyx mori cDNA was cloned that hybridized with Hyalophora cecropia attacin probe and its nucleotide sequence was determined . This cDNA consisted of 846 nucleotides and the deduced amino acid sequence showed that the cDNA encodes an attacin precursor protein . The putative mature protein of B . mori attacin had 70.4, 68.3 and 18.8% identity in amino acid sequences with that of H . cecropia acidic and basic attacins and Sarcophaga peregrina sarcotoxin IIA, respectively . B . mori and H . cecropia attacins and S . peregrina sarcotoxin IIA had two subdomains in each G domain, suggesting that common amino acid residues in the subdomains are conserved during evolution and plays an important role in the activity of the antibacterial proteins . Expression of B . mori attacin gene was rapidly induced by the injection of Escherichia coli cells into B . mori larvae and continued at least for 48 h mainly in fat bodies and hemocytes. Clin Chest Med, 1995 Mar, 16(1), 155 - 71 Community-acquired pneumonia in the intensive care unit; Leeper KV Jr et al.; CAP requiring ICU admission is a distinct clinical entity . The mortality rate of pneumonia in this subset of patients has been unchanged in the past several years . Aggressive diagnostic of strategies to establish the causative pathogens of pneumonia rapidly will enable clinicians to adjust antibiotic therapy appropriately . It is hoped that new adjunctive therapeutic options that positively influence host-related factors and bolster pulmonary antibacterial defense will result in reduced morbidity and mortality. Z Naturforsch {C}, 1995 Mar-Apr, 50(3-4), 167 - 72 Chemical composition and antibacterial activity of Brazilian propolis; Bankova V et al.; Four samples of Brazilian propolis were investigated by GC/MS of different fractions . 32 volatile compounds, (10 of them new for propolis), as well as 12 more polar compounds (one of them new for propolis) were identified . Antibacterial activity was found in some propolis fractions. Br J Rheumatol, 1995 Mar, 34(3), 265 - 9 Small bowel bacterial overgrowth in systemic sclerosis: detection using direct and indirect methods and treatment outcome; Kaye SA et al.; Twenty-four patients with proven systemic sclerosis and with symptoms suggestive of malabsorption (i.e . chronic diarrhoea and weight loss) were investigated for small bowel bacterial overgrowth . Of the patients selected, six were suffering from the diffuse form of the disease . Jejunal aspiration was performed in all patients, and in nine normal volunteers . A specially designed double-lumen sterile catheter was used for this purpose and was introduced via a gastroscope . Twenty of these patients underwent a glucose hydrogen breath test . Eight patients (33%) had significant bacterial counts: > 10(5) colony forming units per ml (cfu/ml) of jejunal fluid . Less than 10(2) cfu/ml were found in the jejunal fluid from the nine control subjects . Glucose hydrogen breath testing was positive in seven patients, all of whom had significant jejunal bacterial growth . Diarrhoea rather than weight loss was shown to be the symptom which correlated best with the presence of bacterial overgrowth . Ciprofloxacin was used in six patients whose diarrhoeal symptoms ceased dramatically within 48 h of commencing the antibiotic . Trimethoprim produced a partial response despite bacterial sensitivity . A disadvantage of the hydrogen breath test is that subsequent antibacterial therapy cannot be specific, as bacterial species, antibiotic sensitivity and resistance are unknown . Systemic sclerosis involving the small intestine in the past has been said to more prevalent in patients with diffuse disease, whereas this study showed a preponderance of patients with long-standing limited cutaneous systemic sclerosis and small bowel involvement. Int Endod J, 1995 Mar, 28(2), 95 - 9 The fate and the role of bacteria left in root dentinal tubules; Peters LB et al.; In this article the question of the relevance and consequences of bacteria remaining in the tubules of root dentine after cleaning and shaping of the root canal space is addressed . A second aim is to discuss the necessity of clinical measures taken to eradicate those bacteria that are presumed to survive there . The available clinical and experimental evidence supports the use of antibacterial dressings in cases where the root canal space remains temporarily unobturated after removal of necrotic and infected pulp tissue . There is no evidence, however, that special measures should be taken to kill the bacteria in the dentinal tubules . Should time permit, a sound obturation technique immediately following the cleaning, shaping and disinfection phases allows the remaining bacteria in the tubules to be either inactivated or prevented from repopulating the (former) canal space . In the vast majority of cases, those bacteria appear not to jeopardize the successful outcome of root canal treatment. Antibiot Khimioter, 1995 Mar, 40(3), 47 - 51 {Lomefloxacin pharmacokinetics in patients in the terminal stage of chronic renal insufficiency, undergoing treatment with programmed hemodialysis}; Kolendo SE et al.; The most frequent complications in patients with the terminal stage of chronic renal insufficiency are infections of various severity . The problem of the antibacterial therapy choice is especially urgent because of a high frequency of antibiotic resistant strains and the necessity to correct the treatment regimens in regard to the severity of the renal failure . The pharmacokinetics of lomefloxacin, a new fluoroquinolone, was studied in the treatment of patients with the terminal stage of chronic renal insufficiency treated by programmed hemodialysis . Lomefloxacin was administered orally in a dose of 400 mg at an interval of 48 hours 24 hours prior to the hemodialysis application . There was observed a decrease in the maximum serum concentration of the drug by comparison to that in healthy persons which could be due to slow absorption of the drug and hyperhydration in the patients because of anuria . In the treatment of such patients it is necessary to provide high serum concentrations of lomefloxacin attainable by using higher single doses of the drug. Vojnosanit Pregl, 1995 Mar-Apr, 52(2), 135 - 41 {Treatment of pneumonia under hospital conditions}; Ponomarev D; A random sample of 24 patients affected by bacterial pneumonia has been investigated whether their illness is treated etiologically . The agents have been detected from the endoscopically obtained samples of blood or chest punctate (percutaneous needle aspirate--PNA) and their sensitivity to antibacterial drugs, used in our institution, have been investigated . The obtained results have been compared to the empirically applied drugs . In only three patients the first given drug corresponded to the later obtained finding of the agent's sensitivity and in one patient third and the fourth drug has been adequate . The rational initial therapy has been proposed on the basis of investigation of the sensitivity of the bacterial pneumonia agents. J Endod, 1995 Mar, 21(3), 137 - 41 Histopathological observations of periapical repair in teeth with radiolucent areas submitted to two different methods of root canal treatment; Leonardo MR et al.; Dogs' teeth with induced chronic periapical periodontitis were treated endodontically by two different methods, and the results were compared . A total of 40 root canals from the upper and lower premolars of two dogs were prepared chemomechanically . In method 1, a high-concentration (5.25%) hypochlorite solution was used during the instrumentation of the root canal, and an antibacterial dressing was applied between sessions, followed by filling of the root canal . In method 2, a low-concentration (0.5%) sodium hypochlorite solution was used as an adjunct to mechanical debridement, and the root canal was filled during the same session . The histopathological results showed that method 1 led to better periapical repair than method 2. Biol Pharm Bull, 1995 Mar, 18(3), 457 - 9 A sapecin homologue of Holotrichia diomphalia: purification, sequencing and determination of disulfide pairs; Lee SY et al.; We purified and characterized a sapecin homologue, named holotricin 1, from the hemolymph of immunized larvae of a coleopteran insect, Holotrichia diomphalia . We determined its complete amino acid sequence and three disulfide pairs . Holotricin 1 consisted of 43 amino acid residues and showed potent antibacterial activity against gram-positive bacteria, but antibacterial activity against gram-negative bacteria was not obvious. Clin J Pain, 1995 Mar, 11(1), 45 - 62 Complications of intrathecal opioids and bupivacaine in the treatment of "refractory" cancer pain; Nitescu P et al.; OBJECTIVE: To test the concept that externalized tunneled intrathecal catheters lead to a high risk of complications, such as meningitis and epidural abscess, and therefore should not be used for durations of intrathecal pain treatment of > 1 week . DESIGN: Prospective, cohort, nonrandomized, consecutive, historical control trial . SETTING: Tertiary care center, institutional practice, hospitalized and ambulatory care . PATIENTS: Two hundred adults (107 women, 93 men) with refractory cancer pain treated for 1-575 (median, 33; total, 14,485) days; 79 patients were treated at home for 2-226 (median, 36; total, 4,711) days . All patients had died by the close of the study . INTERVENTIONS: Insertion of intrathecal tunneled nylon (Portex) catheters (223 in 200 patients) with Millipore filters . The catheter hubs were securely fixed to the skin with steel sutures . Standardized care after insertion: (a) daily phone contact with the patients, their families, or the nurses in charge; (b) weekly dressing change at the tunnel outlet by the nurses; (c) refilling of the infusion containers by the nurses; (d) exchange of the infusion systems when empty (within 1 month) and of the antibacterial filter once a month by specially instructed Pain Department nurses . All contact between the connections of the syringes, cassettes, and needles with the operator's hands was carefully avoided during filling and refilling of the infusion containers and exchange of the antibacterial filters; no other aseptic precautions were taken . MAIN OUTCOME MEASURES: We recorded the rates of perfect function and complications of the systems . The rates of complications recorded in this study with externalized tunneled intrathecal catheters are discussed and compared with the rates reported in the literature with externalized (tunneled and non-tunneled) epidural and intrathecal catheters, as well as with internalized (both epidural and intrathecal) catheters connected to subcutaneous ports, reservoirs, and pumps . RESULTS: The following rates (as a percentage of number of patients) of perfect function and complications of the systems were recorded (the ranges of rates reported in the literature are given in parentheses): perfect function of the system, 93% (31-90%); accidental injury of an unknown epidural tumor followed by an epidural hematoma, 0.5% (0-6%); skin breakdown at the insertion site, 2% (2-50%); postdural puncture headache, 15.5% (10%); external leakage of CSF, 3.5% (4-27%); CSF hygroma ("pseudomeningocele"), 1.5% (4-6.25%); hearing loss and Meniere-like syndrome, 0% (12%); pain on injection, 0% with continuous infusion and 4.5% with intermittent injections (3-36% with intermittent injections); catheter tip dislodgement, 1.5% (6-33%); catheter (system) occlusion, 1% (3-12%); accidental catheter withdrawal, 4% (3-22%); catheter (system) leakage, 1.5% (2.1-26.6%); all mechanical complications, 8.5% (10-44%); local (catheter entry site) infection, 0.5% (2-33%); catheter track infection, 0% (6-25%); epidural abscess, 0% (0.6-25%); meningitis, 0.5% (1-25%); systemic infection, 0% (3%); incidence of all infections (n/treatment days), 1/7,242 (1/168-1/2,446) . CONCLUSIONS: In our population and with the technique of insertion and care reported here, the use of externalized tunneled intrathecal catheters has not been associated with higher rates of complications when compared with earlier reported rates of externalized epidural catheters and internalized (both epidural and intrathecal) catheters connected to subcutaneously implanted ports, reservoirs, and pumps . The opinion that the use of externalized tunneled intrathecal catheters should be restricted only to patients who need pain treatment for < 1 week (because of the potential risk of infection, particularly meningitis and epidural abscess) is unfounded. Urol Nefrol (Mosk), 1995 Mar-Apr, (2), 30 - 3 {The relationship of postoperative thrombotic-hemorrhagic complications to the local acute inflammatory process in patients with prostatic adenoma}; Shabad AL et al.; Clinical, laboratory and pathomorphological investigations evidence for close relationships between acute infectious inflammatory conditions of the prostate and thrombohemorrhagic complications arising both locally and systemically . All these postoperative complications manifesting clinically as acute prostatitis, epididymo-orchitis, urosepsis, bacteriotoxic shock, bleeding, thrombosis and embolism, latent or marked DIC syndrome have underlying local infectious-inflammatory process (postoperative acute prostatitis) . Preoperative detection of local infection (concomitant chronic prostatitis), monitoring of hemocoagulation, antibacterial and antiinflammatory therapy of chronic prostatitis and normalization of blood rheology improve surgical outcomes in prostatic adenoma and lead to less frequent occurrence of both acute inflammatory and thrombohemorrhagic complications. Rev Inst Med Trop Sao Paulo, 1995 Mar-Apr, 37(2), 181 - 3 A case of mycotic keratitis caused by Fusarium solani; Hamdan JS et al.; A 36-year-old black man, without history of systemic disease or ocular trauma developed a corneal infection in his left eye . He was treated with antibacterial antibiotic and corticosteroids for one month prior to diagnosis . Fungal hyphae and chlamydospores were found in a KOH preparation of the corneal scrapings, and positive cultures for Fusarium solani were obtained in Sabouraud dextrose agar . It is emphasized the cautious use of antibiotics and steroids in corneal diseases, and the need of considering the involvement of opportunistic fungi in the etiology of these infections. J Med Chem, 1995 Feb 3, 38(3), 408 - 24 Self-assembly of a quinobenzoxazine-Mg2+ complex on DNA: a new paradigm for the structure of a drug-DNA complex and implications for the structure of the quinolone bacterial gyrase-DNA complex; Fan JY et al.; The quinobenzoxazine compounds A-62176 and A-85226 belong to a novel class of antineoplastic agents that are catalytic inhibitors of topoisomerase II and also structural analogs of the antibacterial DNA gyrase inhibitor Norfloxacin . In vitro studies have shown that their antineoplastic activity is dependent upon the presence of divalent metal ions such as Mg2+ and Mn2+, although the precise role of these ions in the mechanism of action is unknown . In this study we have investigated the structures of the binary complex between the quinobenzoxazines and Mg2+ and the ternary complex between quinobenzoxazine-Mg2+ and DNA . The stoichiometry of the binary and ternary complexes and the biophysical studies suggest that a 2:2 drug:Mg2+ complex forms a "heterodimer complex" with respect to DNA in which one drug molecule is intercalated into DNA and the second drug molecule is externally bound, held to the first molecule by two Mg2+ bridges, which themselves are chelated to phosphates on DNA . There is a cooperativity in binding of the quinobenzoxazines to DNA, and a 4:4 drug:Mg2+ complex is proposed in which the two externally bound molecules from two different 2:2 dimers interact via pi-pi interactions . The externally bound quinobenzoxazine molecules can be replaced by the quinolone antibacterial compound Norfloxacin to form mixed-structure dimers on DNA . Based upon the proposed model for the 2:2 quinobenzoxazine:Mg2+ complex on DNA, a parallel model for the antibacterial quinolone-Mg2(+)-DNA gyrase complex is proposed that relies upon the ATP-fueled unwinding of DNA by gyrase downstream of the cleavable complex site . These models, which have analogies to leucine zippers, represent a new paradigm for the structure of drug-DNA complexes . In addition, these models have important implications for the design of new gyrase and topoisomerase II inhibitors, in that optimization for structure-activity relationships should be carried out on two different quinolone molecules rather than a single molecule. EMBO J, 1995 Feb 1, 14(3), 536 - 45 Functional analysis and regulation of nuclear import of dorsal during the immune response in Drosophila; Lemaitre B et al.; In addition to its function in embryonic development, the NF-kappa B/rel-related gene dorsal (dl) of Drosophila is expressed in larval and adult fat body where its RNA expression is enhanced upon injury . Injury also leads to a rapid nuclear translocation of dl from the cytoplasm in fat body cells . Here we present data which strongly suggest that the nuclear localization of dl during the immune response is controlled by the Toll signaling pathway, comprising gene products that participate in the intracellular part of the embryonic dorsoventral pathway . We also report that in mutants such as Toll or cactus, which exhibit melanotic tumor phenotypes, dl is constitutively nuclear . Together, these results point to a potential link between the Toll signaling pathway and melanotic tumor induction . Although dl has been shown previously to bind to kappa B-related motifs within the promoter of the antibacterial peptide coding gene diptericin, we find that injury-induced expression of diptericin can occur in the absence of dl . Furthermore, the melanotic tumor phenotype of Toll and cactus is not dl dependent . These data underline the complexity of the Drosophila immune response . Finally, we observed that like other rel proteins, dl can control the level of its own transcription. Drug Metab Dispos, 1995 Feb, 23(2), 197 - 200 Disposition of ciprofloxacin in the isolated perfused rat liver; Abadia AR et al.; Ciprofloxacin (CIP), a quinolone with a wide spectrum of antibacterial activity, was studied in the isolated perfused rat liver . Three concentrations (1, 5, and 25 mg/liter) were used in the perfusion medium to check whether hepatic transformation and/or biliary elimination of this drug was dose-dependent . Pharmacokinetic parameters of CIP in the perfusion medium were similar when normalized for the dose at all three concentrations . Some dose-dependent changes were observed in biliary excretion of CIP . CIP biliary clearance and the percentage of excreted drug differed at 25 mg/liter and the lower concentrations . In addition, the chromatograms of the bile samples at the highest dose showed a peak that never appeared at the lower concentrations . This evidence, together with the zwitterion characteristics of CIP, reaching a bile/medium area under the concentration-time curve ratio > 10, suggests that an active transport mechanism is involved in the drug's biliary excretion, as has been demonstrated for its renal elimination. Antimicrob Agents Chemother, 1995 Feb, 39(2), 567 - 70 Inhibitory action of lansoprazole and its analogs against Helicobacter pylori: inhibition of growth is not related to inhibition of urease; Nagata K et al.; The proton pump inhibitors omeprazole and lansoprazole and its acid-activated derivative AG-2000, which are potent and specific inhibitors of urease of Helicobacter pylori (K . Nagata, H . Satoh, T . Iwahi, T . Shimoyama, and T . Tamura, Antimicrob . Agents Chemother . 37:769-774, 1993), inhibited the growth of H . pylori . The growth was inhibited not only in urease-positive clinical isolates but also in their urease-negative derivatives which had no urease polypeptides . AG-1789, a derivative of lansoprazole with no inhibitory activity against H . pylori urease, also inhibited the growth of both strains even more strongly than the urease inhibitors lansoprazole and AG-2000 . Furthermore, the antibacterial activity of omeprazole and lansoprazole was not affected by glutathione or dithiothreitol, which completely abolished the inhibitory activity of lansoprazole against H . pylori urease . These results indicated that the inhibitory action of these compounds against the growth of H . pylori was independent from the inhibitory action against urease. Antimicrob Agents Chemother, 1995 Feb, 39(2), 533 - 8 Antibacterial activities of cefprozil compared with those of 13 oral cephems and 3 macrolides; Fung-Tomc JC et al.; Thirteen oral cephems (cefprozil, loracarbef, cefaclor, cefuroxime axetil, cefpodoxime proxetil, cefetamet pivoxil, cefixime, cefdinir, cefadroxil, cephradine, cephalexin, cefatrizine, and cefroxadine), the cephalosporin class representative cephalothin, cefazolin, and the macrolides erythromycin, clarithromycin, and azithromycin were compared for their antibacterial activities against 790 recent clinical isolates . These oral agents differed in their spectra and antibacterial potencies against community-acquired pathogens. Antimicrob Agents Chemother, 1995 Feb, 39(2), 476 - 83 CP-115,953 stimulates cytokine production by lymphocytes; Riesbeck K et al.; The cytotoxic quinolone CP-115,953 specifically exerts its inhibitory effect upon eukaryotic topoisomerase II . CP-115,953 stimulates DNA cleavage mediated by topoisomerase II with a potency approximately 600 times greater than that of ciprofloxacin, a quinolone antibacterial agent that currently is in clinical use . Because ciprofloxacin has been reported to strongly enhance interleukin-2 production, we considered it important to study the effect of CP-115,953 on interleukin-2 and gamma interferon (IFN-gamma) mRNA and protein expression in mitogen-stimulated human peripheral blood lymphocytes . For comparison, novobiocin and the antineoplastic drug etoposide were also included in the study . CP-115,953 (25 microM) enhanced interleukin-2 mRNA levels up to 8-fold and IFN-gamma mRNA concentrations up to 6.5-fold . In contrast, ciprofloxacin (282 microM) induced mRNAs for interleukin-2 and IFN-gamma up to 20-fold and 7.8-fold, respectively . However, CP-115,953 showed more prolonged kinetics of IFN-gamma mRNA production than ciprofloxacin . At high concentrations (> or = 141 microM), ciprofloxacin was a greater inducer of interleukin-2 production and exhibited a higher level of stimulatory action than CP-115,953 on IFN-gamma synthesis . At low concentrations, however, CP-115,953 (< or = 25 microM) was more potent than ciprofloxacin in inducing interleukin-2 and IFN-gamma synthesis . Etoposide or novobiocin did not influence cytokine mRNA expression . Thus, among the topoisomerase II inhibitors tested, fluoroquinolones are unique in stimulating cytokine synthesis in lymphocyte cultures. Arzneimittelforschung, 1995 Feb, 45(2), 195 - 7 Reduction of in vitro clastogenicity induced by the mixture of optical isomers of nadifloxacin during storage; Takahashi N et al.; The fluoroquinolone antibacterial agent, nadifloxacin (NDFX, CAS 124858-35-1), is a racemic compound . The storage effect on the in vitro clastogenicity of a solution of the racemic compound and a mixture solution of the optical isomers of NDFX, prepared by mixing equal amounts of S- and R-enantiomers, was investigated . The potential of NDFX and the enantiomer mixture, prepared from equal amounts of each S- and R-enantiomer, to induce chromosomal aberrations in vitro was investigated in cultured fibroblasts derived from Chinese hamster lung cells immediately, 2 and 4 weeks after preparation of the test solutions (stored at 20 degrees C, protected from light) using 24 h of continuous treatment method . In the results, NDFX did not significantly increase the incidence of chromosomal aberrations at 200 micrograms/ml regardless of the storage period . On the other hand, the mixture significantly increased the incidence of chromosomal aberrations at 200 micrograms/ml immediately after preparation to an extent similar to that of S-enantiomer alone, but the mixture did not do so after 2 and 4 weeks of storage . Neither S- nor R-enantiomer changed the chromosomal aberration inducibility during storage . The content and optical purity of the test substances in each test solution also did not change during storage . These facts suggested that the molecular condition of each optical isomer in the mixture solution became equivalent to that in the racemic solution during storage periods. J Antibiot (Tokyo), 1995 Feb, 48(2), 134 - 42 CJ-12,371 and CJ-12,372, two novel DNA gyrase inhibitors . Fermentation,isolation, structural elucidation and biological activities; Sakemi S et al.; A fermentation broth of an unidentified fungus (N983-46) was found to produce DNA gyrase inhibitors, CJ-12,371 (1) and CJ-12,372 (2) . Following isolation by solvent extraction and silica gel and ODS (reverse phase) chromatographies, the structures were determined to be novel spiro-ketal compounds with S-configuration at position C-1 . CJ-12,371 and CJ-12,372 inhibit both DNA supercoiling and relaxation mediated by Escherichia coli DNA gyrase . The interaction of these compounds with DNA gyrase appears to be novel in that the compounds inhibit supercoiling and relaxation without blocking religation; thus, no cleavage intermediate of double strand DNA is observed . Both compounds have antibacterial activity against several species of pathogenic Gram-positive bacteria, with MICs between 25 and 100 micrograms/ml . These results suggest that the antibacterial potency of CJ-12,371 and CJ-12,372 is attributed to the inhibition of DNA gyrase . However, the compounds did not inhibit DNA gyrase selectively, as they also inhibited eukaryotic topoisomerase II-mediated relaxation . Semi-synthetic modifications to the dihydroxy motif in CJ-12,371 altered both gyrase- and topoisomerase II-inhibitory activities, but did not enhance selectivity. J Chemother, 1995 Feb, 7(1), 42 - 4 Biapenem versus imipenem in the treatment of experimental intraabdominal infections; Nord CE et al.; A reproducible experimental model of intraabdominal infections in rats has been devised in order to simulate intraabdominal infections in patients . The experimental model was used to compare the efficacy of biapenem with imipenem . Three groups of animals were used, each group consisting of 20 animals . Antibacterial agents were given by injection initially 1 h after surgery and then at 12 h intervals for 12 days . The drugs and amounts of agents given per dose were biapenem 10 mg and imipenem 10 mg, respectively . The control group received 0.9% sterile saline . 80% of the untreated animals died within 3 days . Animals treated with biapenem or imipenem had a significantly decreased mortality and increased cure rates during the experimental period . Only two animals in the two treatment groups died . Biapenem seems to be useful in the treatment of intraabdominal infections. Antibiot Khimioter, 1995 Feb, 40(2), 9 - 13 {Antibacterial and immunomodulating activity of fucoidan}; Zapopozhets TS et al.; The experimental data on the study of the antibacterial and immunomodulating activity of phucoidan, a sulfatated polymer from brown algae (phucan sulfate), were generalized and it was shown that phucoidan was able to markedly inhibit the growth of gramnegative and grampositive organisms and to stimulate immunoreactions of the humoral and cellular types, as well as phagocytosis . The possible use of phucoidan as a drug with associated antibacterial and immunomodulating activity is discussed. Am J Clin Nutr, 1995 Feb, 61(2), 430S - 436S Interface of malnutrition and periodontal diseases; Enwonwu CO; In response to periodontal pathogens neutrophils release oxidants, proteinases, and other destructive factors . The balance between these factors, the antioxidants, and endogenously synthesized antiproteinases determine the extent of periodontal damage . Malnutrition, particularly protein-energy malnutrition involving concomitant deficiencies of antioxidant nutrients, is characterized by impairment in production and cellular actions of the cytokines, diminished acute-phase protein response (APR) to infections, endocrinopathies, defective metabolism of drugs, and impaired response to stress . The APR plays a central role in promoting healing . Additionally, malnutrition elicits adverse alterations in the oral microbial ecology as well as in the volume and the antibacterial and physicochemical properties of saliva . Good dietary practices and optimal nutritional status are therefore important in mitigating the severity of inflammatory periodontal lesions but are likely of limited value if the stimuli from dental plaque are not removed. J Oral Maxillofac Surg, 1995 Feb, 53(2), 131 - 9 The preparation of an autologous saliva for use with patients undergoing therapeutic radiation for head and neck cancer; Sreebny LM et al.; PURPOSE: At the present time there is no general agreement about how to prevent the symptoms and clinical signs that accompany therapeutic irradiation for head and neck cancer . Because saliva is the principal protector of the oral tissues, it is logical to assume that many of these changes are due to the radiation-induced damage to the salivary glands . We have observed that the flow and composition of saliva is normal in most patients before their irradiation . Theoretically, it should, therefore, be possible to collect their saliva before they commence their course of radiation, store it in a "saliva bank," and give it back to them when they undergo radiation . The key to the use of such an autologous saliva is the fabrication of a technique that disinfects or sterilizes the saliva yet preserves its protective properties . The objective of this study was to prepare an autologous saliva that would be used by patients during their irradiation for head and neck cancer . MATERIALS AND METHODS: Stimulated saliva was obtained from healthy subjects; none of the subjects consumed any medications . The saliva was treated by a variety of techniques . Included among them were heat, radiation, filtration, centrifugation, and an antibacterial agent . The samples were analyzed for total protein, amylase, viscosity, and sterility; individual salivary proteins were assessed by sodium dodecylsulfate-polyacrylamide gel electrophoresis . RESULTS: The results showed that beta radiation (> 2.5 kGy) and lyophilization + chlorhexidine (0.03% to 0.12%) could be used to prepare a sterile autologous saliva that retained most of its protective properties. N Engl J Med, 1995 Jan 19, 332(3), 139 - 42 Antibacterial treatment of gastric ulcers associated with Helicobacter pylori; Sung JJ et al.; BACKGROUND . There is a strong association between infection with Helicobacter pylori and gastric ulcers that are unrelated to the use of nonsteroidal antiinflammatory medications . We studied the efficacy of antibacterial therapy without medication to suppress gastric acid for the treatment of patients with H . pylori infection and gastric ulcers unrelated to the use of nonsteroidal agents . METHODS . Patients with gastric ulcers seen on endoscopy and with H . pylori infection confirmed by smear or culture were randomly assigned to receive either a one-week course of antibacterial agents (120 mg of bismuth subcitrate, 500 mg of tetracycline, and 400 mg of metronidazole, each given orally four times a day) or a four-week course of omeprazole (20 mg orally per day) . Follow-up endoscopies were performed after five and nine weeks . The patients and their physicians were aware of the treatment assignments, but the endoscopists were not . RESULTS . A total of 100 patients were randomly assigned to treatment, and 85 completed the trial . At five weeks, H . pylori had been eradicated in 41 of the 45 patients in the antibacterial-treatment group (91.1 percent; 95 percent confidence interval, 82.9 to 99.3) and in 5 of the 40 in the omeprazole group (12.5 percent; 95 percent confidence interval, 2.3 to 22.7; P < 0.001) . The gastric ulcers were healed in 38 of the patients treated with antibacterial drugs (84.4 percent; 95 percent confidence interval, 73.9 to 95.0) and in 29 of those treated with omeprazole (72.5 percent; 95 percent confidence interval, 58.6 to 86.4; P = 0.28) . At nine weeks, ulcer healing was confirmed in 43 of the patients receiving antibacterial therapy and in 37 of those receiving omeprazole (P = 1.0) . The mean (+/- SD) duration of pain during the first week of treatment was 1.9 +/- 2.6 days in the omeprazole group, as compared with 3.6 +/- 3.0 days in the antibacterial-treatment group (P = 0.004) . One year after treatment, recurrent gastric ulcers were detected in 1 of 22 patients (4.5 percent) in the antibacterial-treatment group and in 12 of 23 (52.2 percent) in the omeprazole group (P = 0.001) . H . pylori was detected in the 1 patient with a recurrent ulcer who had received antibacterial treatment and in 10 of the 12 patients with recurrent ulcers who had received omeprazole . CONCLUSIONS . In patients with H . pylori infection and gastric ulcers unrelated to the use of nonsteroidal antiinflammatory drugs, one week of antibacterial therapy without acid suppression heals the ulcers as well as omeprazole and reduces the rate of their recurrence. Presse Med, 1995 Jan 14, 24(2), 55 - 61, 63-5 {Antibiotherapy in the past, present and future}; Bryskier A; The antibiotic era started in 1941 . Several antibiotics were obtained from the fermentation broth, either from moulds (penicillin) or from Actinomyces species (erythromycin) . Numerous antibacterial agents were prepared synthetically such as benzylpyrimidines, 4-quinolones, nitroheterocyclic derivatives, have been developed . Consecutive "waves" of newer antibiotics was helpful to solve some infectious problems but simultaneous emergence of resistant strains has occurred amongst initially susceptible bacteria . This imposes reconsideration of our therapeutic armamentarium and a search for new compounds as well as for new concepts in anti-infective therapy. Przegl Epidemiol, 1995, 49(4), 381 - 4 {Evaluation of antitoxin and antibacterial activity of human preparations of normal immunoglobulin . I . Level of tetanus antitoxin in preparations of IMIG and IVIG}; Zakrzewska A et al.; The level of anti-tetanus antibodies were measured in 791 lots of IMIG and 330 lots of IVIG of human normal gamma globulin . The antibody levels varied 15-80 IU/ml of IMIG lots and 5-20 IU/ml of IVIG lots . Every lot of human normal gamma globulin (IMIG or IVIG) having high anti-tetanus activity may be an acceptable alternative to specific tetanus immune globulin. Nucleic Acids Symp Ser, 1995, (34), 151 - 2 Cytotoxicity and DNA-binding property of non-diynene class of dynemicins and aza-anthraquinones; Shirai R et al.; Dynemicin A is a potent antibacterial and antitumor antibiotic having a striking hybrid structure of both anthraquinone as a DNA intercalator and diynene as a DNA strand breaker . We have investigated the DNA-binding property and cytotoxicity of non-diynene class of dynemicins (H, L, M, O and Q) and several related synthetic tri- and pentacyclic aza-anthraquinones 1a-3a (R = H) and 1b-3b (R = CH3) . Among them, dynemicin H, L, M, O, Q, 1a, 1b and 2b exhibited DNA-binding property . All non-diynene class of dynemicins investigated exhibited intercalative binding activity, however, synthetic aza-anthraquinones 1a-3a did not show such ability . Dynemicin H, Q, 2a, 2b and 3b showed cytotoxicity against HL-60 and K-562 cell lines. J Clin Gastroenterol, 1995, 21 Suppl 1, S155 - 9 Managing acid peptic disease in the Helicobacter pylori era; Marshall BJ; The advent of new diagnostic and therapeutic modalities for Helicobacter pylori allows any physician to offer curative antibiotic regimens to patients with peptic ulcer disease and gastritis . This article describes new management strategies and discusses the advantages of each . In the old strategy, endoscopy was performed on patients with dyspepsia, in the hope of detecting a treatable peptic ulcer . In the new strategy, patients with dyspepsia are investigated with serology to detect those with H . pylori and potentially curable peptic ulcers . Patients with persistent symptoms require a urea breath test and only those who are now H . pylori-negative undergo endoscopy . The cost-effectiveness of these strategies will depend on the expense of each diagnostic test, particularly endoscopy . Whether a noninvasive strategy can be implemented safely may depend also on the incidence of gastric carcinoma in a particular population and the effectiveness of antibacterial therapy at reducing cancer risk. Vestn Khir Im I I Grek, 1995, 154(3), 56 - 60 {The antibacterial and immunocorrective action of ozone therapy in peritonitis}; Vasil'ev IT et al.; Ozone therapy was used in 74 patients with diffuse forms of purulent peritonitis . It allowed to make postoperative lethality 1.7 times less and the amount of complications 1.8 times less as compared with a group of 62 patients where ozone was not used. Adv Exp Med Biol, 1995, 390, 59 - 69 A comparison of active site binding of 4-quinolones and novel flavone gyrase inhibitors to DNA gyrase; Hilliard JJ et al.; The activity of 4-quinolone antibacterials at the enzyme target level is based on the well known and reported observations that 4-quinolone antibacterials target the Gyr A subunit of the DNA gyrase holoenzyme, inhibiting supercoiling while facilitating the "cleavable complex" . Such inhibition can be observed by running the in vitro DNA gyrase supercoiling inhibition assay or the "cleavable complex" DNA gyrase assay . Although potency of the gyrase inhibitor is dependent on many factors including permeability and pharmacokinetics, the inherent potency of a gyrase inhibitor lies in its activity against the target enzyme . We have examined the binding activity of novel flavones {Bioorganic & Med . Chem . Letters 3:225-230, 1993} to Escherichia coli DNA gyrase and have found differences in binding consistent with inhibition of DNA gyrase supercoiling and ability to facilitate the cleavable complex, but of different rank order . {3H}norfloxacin was used in vitro competition studies with test compounds, pBR322 and E . coli DNA gyrase . Binding affinity results indicate the rank order of greatest to weakest binding (ability to compete with {3H}norfloxacin) of test compounds: Levofloxacin = ciprofloxacin > ofloxacin > norfloxacin > flavone compounds (including ellagic acid, quercetin, and compounds 5a through 5n {Bioorganic & Med . Chem . Letters 3:225-230, 1993}) . Such differences in binding ability of the 4-quinolones and flavones to the ternary complex of DNA.DNA gyrase.drug, as compared to the catalytic inhibition and "cleavable complex" data, suggests a more complex binding of flavones than the previously hypothesized models for 4-quinolone binding. Klin Med (Mosk), 1995, 73(6), 38 - 9 {Isolated lymphadenopathy as manifestation of the early stage of Lyme borreliosis}; Lesniak OM; The paper reports 4 cases of early Lyme borreliosis which presented as lymphadenopathy at the site of the tick bite . Erythema migrans and dissemination of infection were absent . The diagnosis was verified via diagnostic titer of antibodies to Borrelia . Administration of antibiotics at the stage of lymphadenopathy contributed to better prognosis . One patient did not receive antibacterial treatment in acute disease and had progression with infection dissemination . Regional lymphadenopathy may serve a clinical marker of early Lime borreliosis. Khirurgiia (Sofiia), 1995, 48(3), 8 - 11 {The basic principles of the antibiotic therapy of burn patients}; Leseva M et al.; Proceeding from many years experience with antibiotic treatment of bacterial infections in burnt patients, accumulated in the Section of Burns and Plastic Surgery, and pertinent literature reports, the basic principles of antibacterial therapy in this contingency of patients are set forth . A detailed protocol is presented, based on: 1) presence of clinical and laboratory evidence of infection and its location, and the most likely causing agents involved, 2) bacteriological data on the commonest causing agents of local and systemic infection in burns, and their sensitivity to antibiotics, 3) duration and surface, deepness and location of the burn injury, and 4) spectrum of action, pharmacokinetics, pharmacodynamics and side effects of the various groups of antibiotics, consistent with the age and concomitant diseases of the patients . A number of antibiotic constellations in cases presenting sepsis where resorting to "blind" therapy is necessitated, are recommended . It is underscored that the protocol suggested is open for modifications, and also that antibiotic therapy efficiency may be anticipated only when combined with adequate infusional and operative management. Akush Ginekol (Sofiia), 1995, 34(2), 33 - 5 {The sensitivity to the preparation cefotaxime of bacteria isolated from newborn infants}; Shopova E et al.; Four hundred forty-four of S . aureus and 54 strains of E . coli were isolated from the neonates, born during the first six months of 1994 in the Maternity Hospital "Maichin dom" . They were tested with the antibiotics--ampicilin, cephamandol and cefotaxime . Our results showed that 14.5% of the tested S . aureus were sensitive to ampicilin (e.g . broad-spectrum penicillins) and 85.5% resistant . Twenty percent of the strains E . coli were sensitive to ampicilin and 80% showed resistance . Fourty nine percent of the tested S . aureus were sensitive to cephamandol (a second generation cephalosporine) and 51% were resistant; 46.6% of the isolated strains E . coli were sensitive to cephamandol and 53.4% were resistant . Over 87% of the tested S . aureus were sensitive to cefotaxime, a third generation cephalosporine, and only 13% were resistant . From the tested strains E . coli 92.3% were sensitive to cefotaxime and 7.7% were resistant . The present study proved a high sensitivity of the isolated strains to cefotaxime . In addition this antibacterial drug showed good tolerance by the neonates when given in two doses per day and a lack of suppressive effect on the normal bacterial flora of the intestinal tract of the neonates. Microbios, 1995, 84(341), 239 - 45 Antibacterial activity of essential oils from Cymbopogon: inter- and intra-specific differences; Pattnaik S et al.; The influence of the genetic background of a plant on the antibacterial activity of essential oil derived from it was investigated . Essential oils from six distinct strains of Cymbopogon were tested against eighteen bacteria . Interspecific and intra-specific differences were evident in the antibacterial activity of the essential oils derived from the the six Cymbopogon strains. Drug Metabol Drug Interact, 1995, 12(2), 151 - 60 Synthesis and characterization of certain thiourea derivatives starting from 1,2,4-triazoline-3-thiones as potential antibacterial and antifungal agents; Kucukguzel I et al.; Several N-substituted-N'-{4-(4-alkyl/aryl-2,4-dihydro-3H-1,2,4-triazole-3-thione -5-yl ) phenyl{thioureas were synthesized in order to examine their antibacterial and antifungal activities . The structures and purity of the synthesized compounds were confirmed by UV, IR and mass spectral data and elemental analysis . However, they were found not to possess significant antibacterial or antifungal activity. Biochimie, 1995, 77(4), 240 - 4 The secondary structure of the insect defensin A depends on its environment . A circular dichroism study; Maget-Dana R et al.; Defensin A is an inducible antibacterial protein isolated from the larvae of Phormia terranovae . The conformation of defensin A has been previously determined by two-dimensional 1H-NMR for concentrations in the range of 4-8 mM in water (Bonmatin JM et al (1992) J Biomol NMR 2, 235-256) . CD spectroscopic data of defensin A at lower concentrations (10(-5) to 10(-3) M) are reported herein . The ellipticity in the 200-240 nm wavelength range for various solvents varies as follows: acetonitrile < water < methanol < HFIP . The magnitude of theta 222 is strongly dependent on defensin concentration in a buffer solution, suggesting an aggregation process . The helical content of defensin A is maximum at a pH value range (7.5-8) for which the optimum antibacterial activity was observed (Cociancich S et al (1993) J Biol Chem 268, 19239-19245). Int Ophthalmol, 1995, 19(1), 29 - 34 Shiva-1: in vitro and in vivo tests of the effects of a novel, synthetic, lytic peptide on ocular cells; Shahsavari M et al.; An investigation was undertaken to determine the toxicity of an intravitreal injection of a novel peptide drug, Shiva-1, in rabbits . The drug, a synthetic peptide modeled after lytic peptides secreted by certain insects, has antiproliferative and antibacterial properties . Initial in vitro experiments showed that the drug, at a concentration of 100 microM, was toxic to both Y-79 retinoblastoma cells and human retinal pigment epithelial cells . A wide range of doses (6-1200 micrograms) was injected into the rabbit vitreous in an attempt to determine the maximum tolerated dose . Retinal toxicity was evaluated clinically, by electroretinography, and by light microscopy . Some localized toxicity was evident at 200 micrograms; all doses of 240 micrograms and above were toxic . While the drug appears to exhibit a narrow range between effective and toxic doses, the results suggest that this and other peptides of similar design merit further investigation for the treatment of proliferative and infectious diseases of the eye. Infection, 1995, 23 Suppl 2, S87 - 90 Oral cephalosporins for use in a parenteral-to-oral switch programme; Rimmer DM; The advent of the newer cephalosporins has increased the feasibility of parenteral-oral switch programmes within this group of antibacterials . The choice of oral compound is governed by consideration of comparative data on in vitro activity and pharmacokinetics, with particular reference to the antibacterial levels achievable in relevant tissues . The establishment of strict patient criteria and an intensive programme of continuous education of the junior doctors are critical elements in the success of a switch programme . We have continuously audited the implementation, practice and financial results of a parenteral-to-oral switch programme from cefotaxime to cefixime during the past 3 years . Results from this audit finally demonstrated a reversal in the upward trend of cephalosporin expenditures in 1994-95. Adv Perit Dial, 1995, 11, 189 - 92 Preliminary evaluation of silver-coated peritoneal catheters in rats; Kathuria P et al.; Silver is known to have powerful antibacterial properties against a variety of micro-organisms and has a low toxicity and a favorable biocompatibility profile . This study was designed to evaluate the effectiveness of silver-coated catheters in preventing early exit-site infection and to assess tunnel morphology . Seven male Sprague-Dawley rats underwent simultaneous implantation of two double-cuffed, silver-coated silicone rubber and standard silicone rubber catheters . Weekly observations and photographs documented exit-site characteristics . The animals were sacrificed and catheters removed and processed for histopathology of the external tunnel at 5 weeks . Exit sites of silver-coated catheters tended to have less inflammation and infection and healed better than those of uncoated catheters; however, these data did not achieve significance using the Wilcoxon signed-rank test . Sections of the external tunnel of well-healing exit sites showed an epithelialized tract with granulation tissue near the cuff and significant invasion of the external cuff by collagen with a mild neutrophilic inflammatory response . In contrast, the histology of the external tunnel of infected exists revealed exudate overlying inflammatory granulation tissue and a variable degree of fibrosis of the cuff . When the exit sites appeared similar, no significant histopathological differences in sinus tract and cuff morphology were noted with either silver or standard catheters . In conclusion, these findings suggest that silver coating of catheters may decrease the incidence of early exit-site infections and allow better ingrowth of the catheter. Pneumonol Alergol Pol, 1995, 63(7-8), 440 - 5 {Ultrasonographic examination of the heart as a basis for determining the cause of inflammatory infiltration changes in the lungs}; Wiatr E et al.; Diagnostic difficulties found in a 41 year old female presenting with fever, chills, fainting spells, tachycardia, hypotension, interstitial consolidation in both lungs and enlargement of the cardiac silhouette on a chest radiogram are discussed . Unsuccessful antibacterial and antituberculous therapy led to a supposition of a collagen disease . The diagnosis of a bacterial endocarditis with bacterial pulmonary emboli was made basing on determination of bacterial vegetation on cusps of the tricuspid valve. Chem Pharm Bull (Tokyo), 1995 Jan, 43(1), 63 - 70 Studies on pyridonecarboxylic acids . III . Synthesis and antibacterial activity evaluation of 1,8-disubstituted 6-fluoro-4-oxo-7-piperazinyl-4H-{1,3}thiazeto{3,2- a}quinoline-3-carboxylic acid derivatives; Segawa J et al.; A series of 1,8-disubstituted 6-fluoro-4-oxo-7-piperazinyl-4H-{1,3}thiazeto{3,2-a}quinoline-3- carboxylic acid derivatives was prepared and evaluated for antibacterial activity . In the 7-piperazinyl series, addition of a fluorine at C-8, which increased the in vitro activity for the 1-hydrogen and 1-methyl analogues and decreased it for the 1-phenyl analogue, improved the in vivo activity of all the analogues . Introduction of a methoxy group at C-8 of the 1-methyl-7-piperazinyl analogue also improved its in vivo antibacterial activity . The effect of 8-substituents on the in vitro and in vivo antibacterial activity of the 1-methyl-7-(4-methyl-1-piperazinyl) series is also discussed. Arzneimittelforschung, 1995 Jan, 45(1), 74 - 80 Quality of cefotaxime sodium preparations; Wetterich U et al.; Cefotaxime sodium (CAS 64485-93-4) is a semisynthetic cephalosporin derivative belonging to the third-generation cephalosporins . Owing to its broad antibacterial activity and its high resistance to beta-lactamases it can be used for a large variety of infections . In the present study the quality standard of 15 different cefotaxime sodium manufacturers from 9 different countries has been examined . The best results were received for the preparation Claforan . None of the 14 other products showed comparable results especially with respect to particulate matter and by-products . The particulate contamination of the 14 foreign products showed relatively high values although they still comply with the limits set by the pharmacopoeias . In contrast, in Claforan very few particles were found in the solution . This is of importance as the drug has to be administered either i.v . as an infusion or i.m . as an injection . Also the amount of by-products measured in the 14 foreign preparations was about 1.5 times higher than the one measured for Claforan . Although these are not critical results, they do indicate that there are marked differences between the quality of the products from different countries which should be taken into account. Pharmazie, 1995 Jan, 50(1), 62 - 5 Chemical composition and biological activity of leaf exudates from some Lamiaceae plants; Sattar AA et al.; Leaf exudates from 39 species, belonging to 26 genera of Lamiaceae, have been isolated and their antibacterial and antiviral activity investigated . Some of the active compounds (ursolic acid, siderol and nepetalactone) were isolated and identified, most of them for the first time in the investigated plants . Some chemotaxonomic conclusions were drawn. J Appl Bacteriol, 1995 Jan, 78(1), 55 - 60 A novel approach to mode of action of cationic biocides: morphological effect on antibacterial activity; Kanazawa A et al.; A new concept for the mode of action of cationic biocides is proposed in which the antibacterial activity of cationic disinfectants is ascribed essentially to molecular organizations of cations within aggregates, i.e . the activity is determined by the size of aggregates and number of active molecules comprising the aggregate . On the basis of the new concept, the morphological effect of disinfectants in aqueous solution on the antibacterial activity is discussed for low molecular weight phosphonium salts with single and double long alkyl chains (carbon number 14) . The proposed new concept can be applied to all phenomena reported previously in antibacterial activity of cationic biocides and this concept is very important from the viewpoint of molecular design of more active cationic biocides. J Antibiot (Tokyo), 1995 Jan, 48(1), 36 - 41 Darlucins A and B, new isocyanide antibiotics from Sphaerellopsis filum (Darluca filum); Zapf S et al.; Two new xanthocillin type antibiotics, darlucin A (1) and B (2), were isolated from fermentations of Sphaerellopsis filum (Darluca filum) . Their structures were established by spectroscopic methods . The darlucins are the first known compounds with a 1,2-diisocyanoalkene moiety . Both compounds exhibited antibacterial, antifungal and weak cytotoxic activities. J Am Anim Hosp Assoc, 1995 Jan-Feb, 31(1), 46 - 55 Adverse side effects of oral antibacterial therapy in dogs and cats: an epidemiologic study of pet owners' observations; Kunkle GA et al.; This epidemiologic study surveyed pet owners for observations of adverse reactions to oral antibacterials which were prescribed to outpatients at a university teaching hospital . Multiple questions were asked of all clients whose dog or cat was treated during the 18-month study . The questionnaire was designed prospectively to define those reactions that clearly seemed to be medication related . In this study, owners noted a significant number of adverse side effects with erythromycin stearate administration to dogs . Trimethoprim-sulfadiazine was used most often in dogs but did not result in a substantial number of adverse reactions. Eksp Klin Farmakol, 1995 Jan-Feb, 58(1), 40 - 2 {An evaluation of the efficacy of chronotheray with heparin and kurantil in patients with chronic pyelonephritis}; Zaslavskaia RM et al.; The effectiveness of traditional therapy (TT) and chronotherapy (CT) with heparin and curantyl was comparatively studied in 80 patients suffering from chronic pyelonephritis . The blood clotting variables were determined every 4 hours before and 2.5-3 weeks after TT and CT in combination with antibacterial therapy . The findings suggest that CT is more effective than TT with heparin and curantyl . With CT, steady-state clinical effects, positive dynamics of laboratory findings and a greater trend to normalization of the circadian organization of hemocoagulation were achieved in earlier periods when lower daily and course doses of the agents were used. Infection, 1995, 23 Suppl 1, S10 - 4 Clinical relevance of intracellular and extracellular concentrations of macrolides; Carbon C; The serum levels of the three macrolides--roxithromycin, clarithromycin and azithromycin--vary considerably . The prediction of the antibacterial effect against extracellular pathogens is based on circulating concentrations of free drug, peak and trough levels, the rate of killing, and the presence of a post-antibiotic effect . Intracellular activity depends on the distribution of the antibiotic and the localization of the bacteria, and is variable . Roxithromycin uptake is greater than that of erythromycin . The intracellular half-life may be long for some compounds (azithromycin > roxithromycin) . The intracellular distribution is bimodal, both in the lysosomes and the cytoplasm, but the mechanisms of uptake have not yet been established . At low pH, accumulation is low and macrolides are less active in an acidic medium . Intracellular concentrations cannot readily be predicted on the basis of extracellular levels . Different models have shown that the greater the intracellular concentration, the better the clinical effect . In addition, the transport of macrolides by cells into the infected focus may play an important role in the therapeutic outcome . These factors influence the clinical indications for macrolides, their dosing regimens and breakpoints . In future, macrolides will be developed that are more selective for intracellular infections, while others, which will achieve significant serum levels, will be useful for a broader range of diseases . However, new compounds should be evaluated in different models of infection before clinical studies are instituted . The analysis of failures remains the most important approach in defining concentration/effect relationships. East Afr Med J, 1995 Jan, 72(1), 56 - 9 Prescribing pattern of antibacterial drugs in a teaching hospital in Gondar, Ethiopia; Aseffa A et al.; The prescribing pattern of antibacterial agents was analyzed by reviewing case notes of 407 patients discharged between October and November 1992 from a teaching hospital in Gondar, North-West Ethiopia . Seventy percent had received one or more antibacterials . Most exposure was in surgical ward (84%) followed by paediatric (82%), orthopaedic (78%), medical (72%), gynaecologic (58%) and obstetric (20%) wards . The antibacterials most frequently prescribed were penicillin G (25%), chloramphenical (24%), and ampicillin (20%) . The total list numbered 13 and included no cephalosporines or quinoline derivatives . The preliminary survey indicated an inappropriate use of antibacterials and suggested the need to develop a policy on hospital antibacterial use. J Biochem (Tokyo), 1995 Jan, 117(1), 42 - 6 Apparent antibacterial activity of catalase: role of lipid hydroperoxide contamination; Kono Y; Escherichia coli was killed by catalase in dose-, time-, and pH-dependent manners . Dialyzed catalase had bactericidal activity, but enzyme which had been heat-denatured or inactivated by pretreatment with 3-aminotriazole plus hydrogen peroxide did not . Cytochrome c and hemoglobin also had bactericidal activity . Thiobarbituric acid-reactive substances were detected in commercial hemoproteins except for horseradish peroxidase and the relationship between the contents of these substances and bactericidal activity was demonstrated . Without the addition of hydroperoxide, hemoproteins except for horseradish peroxidase initiated the oxidation of 2,2'-azino-bis(3-ethylbenzthiazoline-6-sulfonic acid) (ABTS) and catalase caused the peroxidation of linoleic acid . The pH patterns of bactericidal activity, lipid peroxidation, and the oxidation of ABTS were similar . The results indicate that hemoprotein preparations are contaminated with lipid hydroperoxides and it is the decomposition of these contaminants catalyzed by the hemoprotein into alkoxyl/peroxyl radicals that causes bacterial killing. Ter Arkh, 1995, 67(3), 20 - 2 {A trial of the use of the new Russian preparation oxymetacil in patients with chronic nonspecific lung diseases}; Borisova AM; The trial of oxymethacyl was conducted in 20 CNSPD patients . Clinicoimmunological examinations provided evidence on the drug effectiveness as it stimulated cell immunity, phagocytosis, was well tolerated, caused no side effects . The highest response was achieved in combination of oxymethacyl with antibacterial therapy . Normalization of clinical and immunological indices in CNPD patients suggests immunocorrective effect of oxymethacyl. Probl Tuberk, 1995, (1), 38 - 40 {Effectiveness of liposomal antibacterial drugs in the inhalation therapy of experimental tuberculosis}; Kurunov IuN et al.; The model of generalized tuberculosis in BALB/c mice was used to compare efficacy of daily and intermittent (2 times a week) regimens of ultrasound inhalation therapy . This employed water-soluble and liposomal dosages of antituberculous drugs . The highest effect was achieved in daily inhalations of liposomal drugs . In spite of the fact that intermittent regime of the liposomal drugs required a 2-fold lowered dosage, its efficacy was not inferior to daily water-soluble drug therapy and was only by 22% less than maximum . High response to liposomal form stems from prolonged persistence of high rifampicin concentrations in pulmonary tissue. J Asthma, 1995, 32(3), 191 - 7 The macrolide antibacterial roxithromycin reduces bronchial hyperresponsiveness and superoxide anion production by polymorphonuclear leukocytes in patients with asthma; Kamoi H et al.; We investigated the effects of a macrolide antibacterial, roxithromycin, on the generation of free radicals by peripheral polymorphonuclear leukocytes (PMNs) and on the severity of bronchial hyperresponsiveness . Ten asthmatic patients were treated for 3 months with roxithromycin, 150 mg orally once daily; such treatment significantly reduced the production of superoxide anion by PMNs (p = 0.0029) and reduced the bronchial hyperreactivity (p = 0.0016),