Antimicrobial

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), as compared with results in healthy controls . Most of the patients required at least 2 months of treatment with roxithromycin for clinical improvement . We conclude that long-term, low-dose administration of roxithromycin may be useful in treatment of patients with bronchial asthma.

Boll Chim Farm, 1995 Jan, 134(1), 28 - 33
Synthesis of some new 1,3,4-oxadiazoline-2 thione derivatives with antibacterial activity; Mashaly M et al.; Three new 5-{(1-benzoylamino)styren-1-yl}-1,3,4-oxadiazoline-2- thiones and nine of their Mannich bases with some primary and secondary amines and three N-hydroxymethyl derivatives are synthesized . Some of the new derivatives were active against the bacteria Escherichia coli.

Urol Nefrol (Mosk), 1995 Jan-Feb, (1), 22 - 5
{Plasmapheresis in the treatment of complicated forms of acute suppurative pyelonephritis in pregnant women}; Dovlatian AA et al.; Plasmapheresis was carried out in the course of treatment of 46 19-28-year-old females (gestation 13-37 weeks) suffering from complicated acute purulent pyelonephritis (APP) versus 50 controls treated conventionally without plasmapheresis . Nonconventional scheme included antibacterial therapy, infusions, plasmapheresis, surgical interventions . The number of plasmapheresis sessions ranged from 3 to 6 per 1 patient depending on APP severity and efficacy of the treatment . Plasma removal reached 600-900 ml of plasma per session, a total of 2000-2600 ml per course of treatment . Introduction of plasmapheresis made it easier to manage pyoseptic intoxication, to achieve clinico- laboratory remission . The efficacy of treatment increased by 20%.

Ter Arkh, 1995, 67(2), 26 - 9
{The drug prophylaxis of peptic ulcer exacerbations}; Grigor'ev PIa et al.; 453 patients with ulcer located in the duodenal bulb and pyloric part of the stomach in the presence of Helicobacter pylori were examined before and followed up after hospital treatment of the ulcer . The authors findings support the importance of maintenance with current antisecretory drugs and on-demand therapy as well as of combined antibacterial therapy against Helicobacter pylori . Adequate chemotherapy in the ulcer exacerbation was able to reduce the number of recurrences and complications.

Nephrol Dial Transplant, 1995, 10(1), 64 - 9
Cancer antigen 125: a bulk marker for the mesothelial mass in stable peritoneal dialysis patients; Visser CE et al.; Mesothelial cells that line the peritoneal cavity are capable of producing several proinflammatory cytokines such as interleukin-6 and interleukin-8 . Since they are the most numerous cell in the peritoneal cavity when the lining mesothelial cells are included, they may play a major role in the local antibacterial defence mechanism . Cancer antigen (CA)125 is expressed by mesothelial cells (as by other coelomic epithelium-derived cells) and might therefore be considered a marker of the mesothelium . The aim of this study was to determine whether CA125 is a bulk or an activation stage mesothelial cell marker . A positive correlation was found between the mesothelial cell number and the CA125 concentration in dialysate of stable PD patients (P = 0.03) . CA125 release by mesothelial cell cultures during confluence showed that the release per cell was constant in time . Stimulation of mesothelial cells in a confluential phase with IL1 beta, TNF alpha, IFN gamma and TGF beta did not result in an increase in CA125 release . Cell lysis showed that CA125 is also present intracellularly . This implies that release of intracellular CA125 can be a disturbing factor in interpreting the CA125 concentration of dialysate in situations where mesothelial cell death may occur, such as in peritonitis . It can be concluded, that our data show that dialysate CA125 is a bulk marker for the mesothelial cell mass in stable PD patients and can thus provide data on the state of the peritoneal membrane in the follow-up of the individual patient.

Biopolymers, 1995, 37(3), 221 - 40
A review of the utility of soluble peptide combinatorial libraries; Pinilla C et al.; This paper reviews the preparation and use of soluble synthetic combinatorial libraries (SCLs) made up of millions of peptide and nonpeptide sequences for the identification of highly active individual compounds . First presented in 1991, SCLs have been prepared in a number of different lengths and formats, and are composed entirely of L-, D-, and unnatural amino acids . Also, existing peptide libraries have been chemically transformed to yield large diversities of nonpeptidic compounds . This review encompasses the published work from this laboratory using SCLs for the identification of antigenic sequences recognized by monoclonal antibodies, novel peptide agonists and antagonists to opioid receptors, new trypsin inhibitors, novel antibacterials, and compounds that inhibit melittin's hemolytic activity . SCLs offer a fundamental, practical advance in the study of interactions between peptide and nonpeptide sequences and their biochemical or pharmacological targets.

J Endod, 1995 Jan, 21(1), 16 - 20
Effects of antibacterial capping agents on dental pulps of monkeys mechanically exposed to oral microflora; Yoshiba K et al.; The effects of antibacterial drugs on bacterially contaminated dental pulps were investigated in monkeys . Class V buccal cavities with pulpal exposures were prepared and then left open to the oral environment for 24 h . The exposed pulps were capped with alpha-tricalcium phosphate (alpha-TCP) containing a mixture of antibacterial drugs . Either alpha-TCP or Ca(OH)2 was used as a control . Pulpal responses were histologically evaluated after 4 wk . Those teeth capped with alpha-TCP alone showed total pulp necrosis and bacterial growth within the pulp chamber . By contrast, the pulps capped with alpha-TCP containing mixed antibacterial drugs remained almost normal without any necrotic layer, but showed persistent absorbing response to capping materials and no signs of hard tissue barrier formation . In teeth capped with Ca(OH)2, a hard tissue barrier was formed below the exposure site, with a wide loss of pulp tissue . No inflammation was seen under the barrier . These results indicate that mixed antibacterial drugs added to alpha-TCP effectively disinfected pulpal lesions, without destroying any of the sound pulp tissue . However, hard tissue barrier formation was delayed by this mixture as compared with Ca(OH)2.

Antimicrob Agents Chemother, 1995 Jan, 39(1), 247 - 9
A novel glycylcycline, 9-(N,N-dimethylglycylamido)-6-demethyl-6-deoxytetracycline, is neither transported nor recognized by the transposon Tn10-encoded metal-tetracycline/H+ antiporter; Someya Y et al.; A novel tetracycline derivative, DMG-DMDOT {9-(N,N-dimethylglycylamido)-6-demethyl-6-deoxytetracycline} , is one of the glycylcyclines which have a broad antibacterial spectrum, including many tetracyclineresistant bacteria (R.T . Testa, P.J . Petersen, N.V . Jacobus, P.-E . Sum, V.J . Lee, and F.P . Tally, Antimicrob . Agents Chemother . 37:2270-2277, 1993) . The mechanism by which DMG-DMDOT overcomes efflux-based tetracycline resistance was investigated . Tetracycline-resistant Escherichia coli cells carrying an R plasmid encoding the tet(B) gene, which encodes the typical tetracycline efflux pump {TetA(B)} of gram-negative bacteria, were as susceptible to DMG-DMDOT as was the tetracycline-susceptible host . When mid-log-phase cells carrying the tet(B) gene were incubated with a subbactericidal concentration of DMG-DMDOT (0.5 micrograms/ml) for 2 h, a significant amount of the TetA(B) protein was detected in the cell membrane by Western blotting (immunoblotting) with an anti-carboxyl-terminal antibody, similar to the case in which tetracycline was used as the inducer, indicating that the tet repressor, TetR, can recognize DMG-DMDOT as an efficient inducer . Everted membrane vesicles prepared from cells producing the TetA(B) protein showed absolutely no transport activity for DMG-DMDOT . Furthermore, the presence of excess DMG-DMDOT had no effect on the tetracycline transport activity of the everted vesicles, indicating that DMG-DMDOT is not recognized as a substrate by the TetA(B) protein.

Scand J Infect Dis Suppl, 1995, 96, 17 - 23
Changing role of carbapenems in the treatment of lower respiratory tract infections; Lode H et al.; The acquisition of antibiotic-resistance genes by virtually all major bacterial pathogens is currently a world-wide phenomenon . This problem is especially evident in nosocomial lower respiratory tract infections (LRTI) . Carbapenems like imipenem and meropenem offer interesting antibacterial activities and beta-lactamase-stability, as well as adequate pharmacokinetic characteristics, to cover most of the pathogens involved in moderate to severe community-acquired and nosocomial LRTI . In contrast to imipenem, meropenem is not nephrotoxic and offers the advantage of greater stability against renal dehydropeptidase-I, so no concomitant application of an enzyme inhibitor is necessary . Meropenem can also be given by intravenous infusion or injection without the nausea and vomiting often associated with the administration of imipenem/cilastatin . Preliminary results with meropenem in LRTI show excellent cure rates and good tolerance for this new carbapenem.

Vestn Ross Akad Med Nauk, 1995, (5), 19 - 23
{Several mechanisms of immunological adaptation in the etiology of subacute infectious endocarditis}; Belokrinitskii DV et al.; The paper deals with the possibility of identifying the persons predisposed to the development of subacute septic endocarditis (SSE), with the prediction of the course of the disease and the clarification of reasons for the inefficiency of antibacterial therapy . The studies performed revealed the impairment of cooperative interaction of the immune system, which prevents it from fulfilling its main task, i.e . to make an immunological surveillance over the maintenance of internal constancy . Imperfection of this function in SSE patients and rheumatic heart diseases is based on the body's sharply limited adaptation which results from the genetically determined low values of the immune functional reserve realizable by the level of intracellular energy processes which are substantially lower in SSE patients, as evidenced by the studies conducted . This is very important for predicting whether it may develop in some patients with rheumatic diseases . The necessity of using large doses of antibiotics decreases the activity of intracellular processes to a greater extent, aggravating primarily phagocytic function, as reflected in the efficiency of antibiotic therapy.

Probl Tuberk, 1995, (3), 25 - 7
{Tactivin in combined treatment of patients with pulmonary tuberculosis associated with gastrointestinal diseases}; Zhukova EM; Tactivin was tried in combined therapy of 49 new-onset cases with destructive pulmonary tuberculosis and gastrointestinal lesions . 52 controls received antibacterial drugs alone . Tactivin increased T-lymphocyte count and improved their subpopulations proportion in a shorter period of time . Immunochemotherapy contributed to efficacy of the main and associated disease treatment . Healing of the destruction foci occurred in 87% versus 70% in controls, side effects of antibacterial drugs and exacerbations of gastrointestinal diseases arose 2-2.5 times less frequently.

Khirurgiia (Mosk), 1995, (2), 27 - 31
{Results and substantiation of surgical strategy in acute suppurative-destructive pyelonephritis in pregnant women}; Doblatian AA; The effectiveness of treatment of acute purulent pyelonephritis in 2.256 pregnant women from 1986 to 1992 was analysed . 95-97% of them had diffuse purulent (nondestructive) pyelonephritis which was cured by drug treatment . Pyodestructive manifestations (apostematosis, carbuncle, abscess of the kidney) of uni- (84.8%) and bilateral (15.2%) pyelonephritis were found in 85 (3.8%) of the patients . Signs of pyoseptic intoxication predominated in the clinical picture . Antibacterial and detoxification therapy was applied in the pre- and postoperative periods . The choice of the surgical tactics and operative method was based on the peculiarities of the clinical course, the revealed complications, and the anatomical changes in the kidney . Nephrostomy and antibacterial therapy are sufficient for curing the apostematic form . Patients with a bilateral affection were treated by operative stage-by-stage kidney drainage (nephrostomy) . When economical operations were ineffective clinically (9.4%), secondary nephrectomy was indicated . Primary nephrectomy is an adequate surgical intervention in cases of a total destructive process in the kidney, grave septic manifestations, and a toxic response of the liver . The high proportion of nephrectomies (37.6%) is explained by the clinicoanatomical severity of focal-purulent pyelonephritis and its complications (sepsis) which hazard the life in pregnancy . Pliant surgical tactics in the treatment of severe forms of pyodestructive pyelonephritis ensured clinical cure of 96.5% of patients and uneventful delivery in 91.8% of cases . Death occurred from sepsis and bacteriotoxic shock which developed due to purulent pyelonephritis of pregnancy.

Rapid Commun Mass Spectrom, 1995, 9(7), 597 - 603
High resolution electrospray mass spectrometry with a magnetic sector instrument: accurate mass measurement and peptide sequencing; D'Agostino PA et al.; The accurate molecular weights for a series of 37 unknown synthetic peptides, used in research studies involving synthetic vaccines, antibacterial peptides or the de novo design of helical peptides and proteins, were determined with a magnetic sector instrument . All data were obtained with external calibration over a wide mass range during magnetic scanning . Errors between observed and theoretical monoisotopic molecular weights were typically in the 5-60 ppm range for the unknowns at sector resolutions between 2500 and 9000 (10% valley) . Isotopic clusters for charge states up to 10+ were resolved through the use of high resolution . Collisionally activated dissociation (CAD) in the electrospray interface resulted in product ions that enabled either full or partial sequencing of most unknown peptides of molecular weights below 2000 Da . The complete primary sequence for one peptide was determined and the importance of high resolution was demonstrated by the differentiation of lysine from glutamine, two amino acids differing in residue mass by only 0.0364 Da . Two other peptides, with identical monoisotopic masses, but different primary sequences, were differentiated based on CAD-MS data.

Antibiot Khimioter, 1995 Jan, 40(1), 22 - 6
{Problems of rational chemotherapy and the role of cefmetazole in their solution}; Iokota T; The paper presents an analysis of the most actual problems of modern antibacterial chemotherapy: mechanisms and distribution of resistance in the most significant clinical gram-positive and gram-negative organisms . Approaches to their solution based on the use of cefmetazole and other cephamycins are indicated.

Anesteziol Reanimatol, 1995 Jan-Feb, (1), 40 - 1
{Experience in intensive therapy of diffuse peritonitis in children}; Marochkov AV et al.; The authors analyze their experience gained in the treatment of diffuse peritonitis in 51 children . The principal components of intensive therapy were effective antibacterial therapy, infusion therapy and parental feeding, prolonged peridural blocking and drug-induced sympathetic blocking, autotransfusions of UV-irradiated blood, and hemoperfusion . The activity of the gastrointestinal tract recovered in all the 51 patients, their clinical and laboratory parameters normalized, and the children were discharged in good condition.

Acta Gastroenterol Belg, 1995 Jan-Feb, 58(1), 1 - 20
The 1994 G . Brohée Lecture (Los Angeles) . The scientification of gastroenterology during the 20th century; Kirsner JB; At the occasion of the Georges Brohee Lecture presented at the 10th World Congress of Gastroenterology in Los Angeles (1994), the author makes a brief history of Georges Brohee (1887-1957), Belgian Surgeon and Radiologist who promoted modern Gastroenterology, in particular by founding the Belgian Society of Gastroenterology in 1928 and by organizing the first International Congress of Gastroenterology in Brussels in 1935 . His continuing efforts culminated in the constitution of the "Organisation Mondiale de Gastro-enterologie" (OMG) which prepared the first World Congress of Gastroenterology for 1958 . In the second part, the author continues his description of the scientific development of Gastroenterology during the 20th century . The following topics are treated: gastrointestinal endoscopy, enteric microflora with emphasis on the discovery of Helicobacter pylori, of Tropheryma Whippleii and of antibacterial agents, gastrointestinal immunology.

Eur J Clin Pharmacol, 1995, 48(3-4), 299 - 304
Changes in the use of antibacterial drugs in the countries of central and eastern Europe; Kiivet RA et al.; Use of systemic antibacterial drugs in the countries of central and eastern Europe (CCEE) has been studied using the defined daily doses (DDD) methodology . For the comparison, national wholesale data from Bulgaria, the Czech Republic, Estonia, Hungary, Lithuania, Slovakia, Slovenia and Romania for the years 1989 and 1992 were used, i.e . for the years before and after the rapid sociopolitical changes in these countries . Substantial differences in the patterns of antibacterial drug use between countries as geographically and economically similar as the CCEE were observed . The general sales of antibiotics varied almost twofold among the CCEE and had decreased in most of the CCEE during the study period . The proportion of tetracyclines in the sales of 1992 ranged from 10% in Slovenia to 49% in Estonia, and that of broad-spectrum penicillins from 6% in Estonia to 40% in Slovenia . The use of narrow-spectrum penicillins varied within the range of 4% in Bulgaria to 38% in Slovakia, and had decreased during the study years in all countries . Aminoglycosides accounted for 5-12% of all antibacterials in Bulgaria, Estonia, Lithuania, Romania and Slovakia in the study period, and these countries, with the exception of Slovakia, also had a high consumption of chloramphenicol . In 1992, by far the most popular antiinfectives in the CCEE were doxycycline, ampicillin and co-trimoxazole, which ranked among the top ten drugs in all countries studied.(ABSTRACT TRUNCATED AT 250 WORDS)

Probl Tuberk, 1995, (4), 5 - 6
{Incidence of tuberculosis and its prevention in medical personnel of antituberculosis institutions}; Kovaleva SI et al.; Incidence rate of tuberculosis was ascertained in medical and paramedical staff of antituberculosis institutions (ATI) for adults . For the period 1987-1993 tuberculosis developed in 38 subjects, i.e . 4 times more frequently than in the rest adult population of Russia . The physicians catch the infection 1.2 times less frequently than paramedical personnel . The highest morbidity was observed in the staff of clinical, bacteriological and pathological laboratories . The course of tuberculosis in ATI staff is favourable due to early detection and long-term treatment but is characterized by frequent attendant diseases, resistance and intolerance to antibacterial drugs . Preventive treatment of ATI staff in a special sanatorium enhances their resistance to M . tuberculosis infection and reduces this infection prevalence in tuberculosis contacts.

Probl Tuberk, 1995, (4), 37 - 40
{Biological properties of Mycobacterium tuberculosis in relation to sensitivity to antibacterial preparations}; Gol'shevskaia VI et al.; Biological properties of M . tuberculosis were investigated in 265 patients with tuberculosis of respiratory organs . Slow but more massive growth in culture medium is characteristic for drug-resistant M.tuberculosis . 32 patients discharging drug-resistant M.tuberculosis had unstable drug resistance to isoniazid, kanamycin, ethambutol and streptomycin . It is suggested that drug-resistant M.tuberculosis by virulence are similar to sensitive varieties.

Int Orthop, 1995, 19(3), 157 - 61
Biodegradable implants for potential use in bone infection . An in vitro study of antibiotic-loaded calcium sulphate; Mousset B et al.; Local antibiotic therapy by diffusion from plaster of Paris beads has proved promising in bone surgery . Sustained local delivery depends on thermostability, so we tested the antibacterial activity of 11 antibiotic solutions after storage at 37 degrees C using a microbiological method . Cephalosporins and penicillins were unstable, but aminoglycosides remained fully stable with 100% activity after 2 weeks . About 60% of the initial bactericidal activity of quinolone, glycopeptides and sodium fusidate were still detectable after 2 weeks . Release of these antibiotics from plaster of Paris beads was evaluated in vitro . Even those in the same family differed in their release rate . Plaster beads with sodium fusidate were the most effective association . A therapeutic level of glycopeptides, aminoglycosides and amoxicillin was leached for about 3 weeks . Cephalosporins and sodium amoxicillin were released in 2 to 3 days, and quinolone beads were too brittle to be used . Plaster of Paris, which is cheap, biocompatible and biodegradable, is an excellent carrier for sodium fusidate, aminoglycosides and glycopeptides.

Antonie Van Leeuwenhoek, 1995, 67(3), 229 - 42
The nonribosomal peptide biosynthetic system--on the origins of structural diversity of peptides, cyclopeptides and related compounds; Kleinkauf H et al.; A variety of peptides have been detected in microorganisms . Some have found applications in various fields, for example the classical beta-lactam antibiotics, immunosuppressors like cyclosporin, promising new antibacterials like teichoplanin or daptomycin and antifungals like echinocandin . For none of these has it been established how their complicated biosynthetic pathways have evolved or what functions they fulfill within or for their producers . So it is unclear what selection processes limit the range of their structural analogues within various groups of microorganisms . We here consider recent data in the field of biosynthesis and how they may suggest mechanisms of genetic diversity . These may illustrate the complexity of genetic and intracellular organization of biosynthetic pathways and indicate the cellular context of some metabolites related to the complex background of the production of each metabolite . Research focusing on various targets like the increase of productivity of fermentations or the spread of resistances to antibacterials is slowly being understood.

Lik Sprava, 1995 Jan-Feb, (1-2), 65 - 7
{A new method for treating patients with chronic prostatitis}; Boiko MI; A new preparation is reported for treatment of chronic inflammation of the prostate, which substantially lowers rates of patients' complaints and depresses the secretion leucocyte reaction . Prostatilen was shown to be capable of normalization of immunity status of the chronic prostatitis patients thus lowering the microbial index of the cultured prostate secretion microorganisms . The following new nonantibacterial strategy of treatment of chronic prostatitis patients is proposed: prostatilen given as a single agent or in combination with immunomodulators and physiotherapeutic methods . Antibacterial therapy is to be instituted on a short-term basis only during the period of exacerbation of the inflammatory process.

Lancet, 1994 Dec 24-31, 344(8939-8940), 1748 - 50
Why monitor peak vancomycin concentrations?
Saunders NJ.
Peak and trough serum concentrations are routinely measured to monitor vancomycin therapy . Optimal therapy depends upon maintaining a concentration above that necessary for antibacterial activity and is therefore determined by the trough concentration . I determined the post dose increases in serum drug concentrations in routine clinical practice in adult patients without renal failure . Mean increases of 16.6 mg/L (SD 6.1) (peak samples collected 1 h post infusion) were measured from 165 paired samples . The results suggest that as long as trough concentrations do not exceed 15 mg/L, peak levels will not exceed normally accepted safe concentrations, and therefore do not need to be measured.

EMBO J, 1994 Dec 15, 13(24), 5958 - 66
Insect immunity . A transgenic analysis in Drosophila defines several functional domains in the diptericin promoter; Meister M et al.; Diptericins are antibacterial polypeptides which are strongly induced in the fat body and blood cells of dipteran insects in response to septic injury . The promoter of the single-copy, intronless diptericin gene of Drosophila contains several nucleotide sequences homologous to mammalian cis-regulatory motifs involved in the control of acute phase response genes . Extending our previous studies on the expression of the diptericin gene, we now report a quantitative analysis of the contribution of various putative regulatory elements to the bacterial inducibility of this gene, based on the generation of 60 transgenic fly lines carrying different elements fused to a reporter gene . Our data definitively identify two Kappa B-related motifs in the proximal promoter as the sites conferring inducibility and tissue-specific expression to the diptericin gene . These motifs alone, however, mediate only minimal levels of expression . Additional proximal regulatory elements are necessary to attain some 20% of the full response and we suspect a role for sequences homologous to mammalian IL6 response elements and interferon-gamma responsive sites in this up-regulation . The transgenic experiments also reveal the existence of a distal regulatory element located upstream of -0.6 kb which increases the level of expression by a factor of five.

Pharmacoeconomics, 1995 Jan, 7(1), 49 - 62
Pharmacoeconomic analysis of empirical therapy with ceftazidime alone or combination antibiotics for febrile neutropenia in cancer patients; Dranitsaris G et al.; There is evidence to suggest that single-agent broad spectrum antibacterials may be cost-effective alternatives to combination antibiotics for the empirical management of febrile neutropenia in cancer patients . The objectives of the present study were 2-fold . The first objective was to compare the clinical effectiveness of ceftazidime monotherapy with that of 2 combination antibiotic regimens in cancer patients with febrile neutropenia . The 2 comparator regimens consisted of tobramycin plus piperacillin, either with (regimen 'CAP') or without (regimen 'AP') cefazolin . The second objective was to perform a cost-effectiveness analysis of the 3 regimens . Meta-analysis of randomised comparative trials between the 3 therapy groups was performed to determine the average overall response rate after 3 to 5 days of treatment . Seven clinical studies were selected for analysis . The overall incidence of adverse drug reactions (ADRs) was determined using the results of comparative and noncomparative studies . A comparative cost-analytic model was applied from a hospital perspective . The costs of primary therapy, hospitalisation, laboratory tests, routine patient care and treating ADRs were calculated, as were future costs . Monotherapy with ceftazidime was associated with an overall response rate of 63.5% and mean per-patient costs of $Can12,000 to $Can14,000 . In comparison, regimen AP was associated with an overall response rate of 58.8% and mean costs of $Can13,000 to $Can16,000 per patient . The overall response rate in patients receiving CAP was 75.3%, and the mean cost per patient was $Can11,000 to $Can12,000 . Thus, regimen CAP was the most cost-effective therapy from a hospital perspective.

Proc Natl Acad Sci U S A, 1994 Dec 6, 91(25), 12031 - 5
Disruption of a topoisomerase-DNA cleavage complex by a DNA helicase; Howard MT et al.; The type II DNA topoisomerases are targets for a variety of chemotherapeutic agents, including the antibacterial quinolones and several families of antitumor drugs . These agents stabilize an enzyme-DNA cleavage complex that consists of the topoisomerase covalently linked to the 5' phosphates of a double-stranded DNA break . Although the drug-stabilized cleavage complex is readily reversible, it can result in cell death by a mechanism that remains uncertain . Here we demonstrate that the action of a DNA helicase can convert the cleavage complex into a nonreversible DNA break by displacing DNA strands from the complex . Formation of a nonreversible DNA break, induced by a DNA helicase, could explain the cytotoxicity of these topoisomerase poisons.

Am Fam Physician, 1994 Dec, 50(8), 1677 - 84, 1687
Preventive oral health care: a review for family physicians; Lokshin MF; Good oral health is essential for both good nutrition and systemic health, in addition to the ability to taste, chew, swallow and speak . Oral diseases include dental caries, periodontal disease, oral mucosal alterations, precancerous lesions and cancer, and oral trauma . Dental caries can be prevented through good oral hygiene and regular professional cleaning, a healthy, low-sugar diet and the use of fluoride and dental sealants . Periodontal disease can be delayed by brushing with fluoride and obtaining professional scaling . Antibacterial mouthwashes may also be helpful . Careful denture cleaning and regular observation for medication side effects can decrease periodontal disease . Tobacco is the most common cause of cancerous oral lesions . Trauma can be avoided by wearing proper protective gear during contact sports and while riding bicycles and motorcycles . Persons in lower income and educational groups have a higher risk of poor oral health . Regular attention to this area by family physicians will decrease the chance of oral disease in patients.

Am J Respir Cell Mol Biol, 1994 Dec, 11(6), 651 - 63
Pseudomonas stimulates interleukin-8 mRNA expression selectively in airway epithelium, in gland ducts, and in recruited neutrophils; Inoue H et al.; Neutrophils may play important roles in chronic airway diseases . Pseudomonas is a common pathogen in some chronic airway diseases, and expression of the neutrophil chemoattractant interleukin-8 (IL-8) is induced by Pseudomonas in various cells in vitro . Here we examine the localization of IL-8 mRNA expression after incubating human and dog bronchi with Pseudomonas supernatant in vitro . To examine IL-8 expression in recruited neutrophils, we also superfused the dog bypassed tracheal segment with Pseudomonas supernatant in vivo and measured neutrophil number and IL-8 concentration in luminal fluid; simultaneously, we introduced Pseudomonas supernatant by catheter in a peripheral airway . After 6 h, we analyzed IL-8 mRNA expression and localization in removed tissue . Unincubated bronchi showed no IL-8 mRNA expression, but incubation with Pseudomonas supernatant in vitro resulted in IL-8 mRNA expression in surface epithelial, gland duct, and a subpopulation of serous gland cells . In vivo, introduction of Pseudomonas supernatant into dog trachea and peripheral airways caused IL-8 mRNA expression in epithelial and gland duct cells but also in the recruited neutrophils . Pseudomonas lipopolysaccharide alone was without effect in vitro and in vivo . We conclude that Pseudomonas products, but not lipopolysaccharide, stimulate IL-8 expression in airways and that this expression occurs primarily in surface epithelial and gland duct cells, thus bringing the chemoattractant to the bacterial site . Furthermore, IL-8 expression in recruited neutrophils provides a potential mechanism for positive feedback of this protective antibacterial response.

J Hosp Infect, 1994 Dec, 28(4), 315 - 21
The assessment of the risk of cross-infection with a multi-use nasal atomizer; Spraggs PD et al.; Atomizers working on the Venturi principle are used by otolaryngology departments in the UK to spray cocaine and other local anaesthetic and vasoconstricting solutions into the nasal cavities . These devices are rarely cleaned, nor is the cocaine in the reservoir changed between patients . This study aimed to assess the risk of cross-infection with such an atomizer of the Down's design . Nutrient broth from a sterile atomizer was sprayed into the nasal cavities of 12 healthy volunteers on three occasions, the tip of the nozzle was withdrawn between sprays into the right nostril, but not between sprays into the left . On each occasion the tip of the nozzle, a nutrient broth rinse of the inner tube of the nozzle and the residue of broth in the reservoir of the atomizer were cultured and the colonies compared with those from a nasal swab collected previously . The results show transmisson of bacteria from the nasal vestibule on to the tip, into the nozzle and into the reservoir of the atomizer . Examination of the minimum inhibitory concentration values of 10% cocaine with and without Nipasept preservative indicated poor antibacterial properties . We conclude that the use of an atomizer on more than one patient poses a risk of cross-infection, and recommend their replacement with a single-use disposable nasal atomizer.

Comp Biochem Physiol B Biochem Mol Biol, 1994 Dec, 109(4), 709 - 13
Antibacterial protection in Marthasterias glacialis eggs: characterization of lysozyme-like activity; Stabili L et al.; Eggs from Marthastherias glacialis exert antibacterial action on marine bacterial strains and show a lysozyme-like activity . This one depends on pH and ionic strength of sample and reacting medium . This hydrolase, purified by gel filtration and ion-exchange chromatography, could be responsible for the bacterial growth inhibitory activity observed.

Analyst, 1994 Dec, 119(12), 2757 - 9
Effect of temperature and diet composition on residue depletion of oxytetracycline in cultured channel catfish; Luzzana U et al.; Oxytetracycline is an antibacterial agent widely used in fish farming . The normal method of administration of oxytetracycline to the fish is to mix the drug into the feed . As a consequence, the concentration of the drug in feed, together with the preparation and the composition of feed, can influence the disposition of the drug itself . An experimental study was carried out to evaluate the residue depletion of oxytetracycline from muscle tissue of channel catfish (Ictalurus punctatus) fed different medicated diets . Three hundred channel catfish were randomly divided into six tanks (50 fish per tank), maintained at water temperatures of 18 degrees C (three tanks) and 23 degrees C (three tanks) . The animals were fed with three diets, differing in their energy content and composition, for the duration of the experiment oxytetracycline was added to the diets at a level of 7500 mg kg-1 for 7 d . After cessation of the treatment, five fish from each tank were killed on days 1, 3, 8, 13, 18, 24, 30, 35 and 40 . Oxytetracycline residues in muscle tissue were determined by high-performance liquid chromatography . The results indicate that the energy level and chemical composition of the medicated diets administered to channel catfish influence oxytetracycline disposition in fish, and that temperature is an important factor in conditioning the reported dietary effects . Therefore, formulation of specific diets to administer drugs to farmed fish could assure better bioavailability of the chemotherapeutant and shorter withdrawal times.

Jpn J Antibiot, 1994 Dec, 47(12), 1762 - 8
{A clinical study on chemotherapies for chorioamnionitis}; Chimura T; Effects of imipenem/cilastatin (IPM/CS) therapy, flomoxef (FMOX) therapy and combined ceftazidime + aspoxicillin (CAZ/ASPC) therapy as initial therapies for chorioamnionitis were assessed clinically . 1 . The subjects were 49 women with threatened abortion and 29 with premature rupture of membranes (PROM), complicated in all cases by chorioamnionitis . The inflammation was treated with IPM/CS in 19 patients, FMOX in 39, CAZ in 11, and CAZ/ASPC in 9 . 2 . The response rate to therapy for chorioamnionitis was 95.9% (47/49) in the threatened abortion group . Of the 49 patients in this group, 16 (32.7%) underwent premature labor . Of the therapies administered, IPM/CS tended to prevent premature labor more frequently than did any other therapy . The latent period (from rupture of membranes to delivery) was equal to or longer than 7 days in the PROM group . The percent prolongation of the latent period in these patients (55.5%) was significantly greater than that previously obtained with penicillin therapy . 3 . The bacterial elimination rate was 50.9% (29/57) . Of the 36 bacterial isolates, 66.7% were Gram-positive bacteria . The bacteriological efficacy rate was 89.7% (26/29) . These results suggest that antibacterial agents effective against Gram-positive bacteria should be selected for treatment of chorioamnionitis, and that IPM/CS therapy is particularly useful considering the drug's good transfer into amniotic fluid and its antibacterial spectrum.

Jpn J Antibiot, 1994 Dec, 47(12), 1637 - 67
{Basic and clinical studies on biapenem (L-627) in obstetrics and gynecology}; Matsuda S et al.; We investigated biapenem (BIPM, L-627) a newly carbapenem antibiotic, for its antibacterial activity, tissue penetration, clinical efficacy and bacteriological effect in obstetric and gynecological infections, and obtained the following results . 1 . Antibacterial activity: MICs of L-627 against 149 strains isolated from 80 patients in this clinical trial were examined and compared with those of imipenem (IPM) and ceftazidime (CAZ) . The MIC50 and MIC90 of L-627 against the isolates were 0.2 and 12.5 micrograms/ml, respectively . Those of IPM were 0.2 and 6.25 micrograms/ml, respectively . The antibacterial activity of L-627 was quite similar to that of IPM, and was superior to that of CAZ . 2 . Tissue and retroperitoneal fluid penetration: The peak levels in venous and uterine arterial sera were 24.0 and 26.2 micrograms/ml, respectively, after 300 mg drip infusion . The peak levels in the uterine or adnexal tissues were 2.39-9.60 micrograms/g, and 0.2 microgram/g of L-627 was detected at 275 minutes after administration . Peak levels in retroperitoneal fluid were 8.7 +/- 1.7 micrograms/ml at 1 hour after the completion of 30 minutes drip infusion (300 mg) and 7.9 +/- 0.2 micrograms/ml at 30 minutes after 300 mg 60 minutes drip infusion (300 mg) . These levels expected the MICs against main pathogenic organisms . 3 . Clinical results: L-627 was given to the following 144 patients (No . of analytical subjects) at a daily dose of 0.3-1.2 g for 2-13 days: intrauterine infections (54), adnexitis (36), parametritis (17), pelvic peritonitis (27), bartholins abscess (6) and other infections (4) . The clinical efficacy was 93.1% (134/144) and the eradication rate against isolated organisms was 88.7% (110/124) . Side effects were observed in 2 patients: eruption (1) and vomiting with numbness of the tongue (1) . Abnormal change in laboratory test results included increase in eosinophils in 1, increase in GOT, GPT and gamma-GTP in 1 and increase in GPT and A1-P in 1, but all of these abnormalities were very mild and withdrawal of the drug was not required . Our results suggest that this drug is useful in the treatment of gynecological infections.

Pharm Acta Helv, 1994 Dec, 69(3), 141 - 8
Formulation and in vitro study of antibacterial vaginal suppositories; Regdon G Sr et al.; Vaginal suppositories frequently used in gynaecological therapy were studied . Several antibacterial pharmacons are used for the topical treatment of vaginitis of various origins . In view of the fact that the liberation of the given active substance and the subsequent therapeutic effect may be improved or inhibited by the vehicle, our aim was to find the optimal suppository base for vaginal suppositories containing sulfadimidine, chloramphenicol and gentamicin sulfate by means of in vitro experiments . On the basis of breaking hardness, disintegration time and spreading properties the French Suppocire NA product, and compositions of macrogols with lower molecular weight proved to be the best lipophilic and hydrophilic bases, respectively . Among the lipophilic bases the in vitro drug liberation of Suppocire NA was significantly better (P < 0.05) than the other lipophilic bases . This vehicle is recommended for the topical treatment of vaginitis, as these suppositories have the further advantage that they can easily be produced on a magistral, galenical or industrial scale as well.

J Antibiot (Tokyo), 1994 Dec, 47(12), 1526 - 40
Studies on orally active cephalosporins . II . Synthesis and structure-activity relations of new {(E) or (Z) 3-substituted carbamoyloxy}-1-propenyl cephalosporins; Negi S et al.; In an effort to find a new oral cephalosporin with well-balanced antibacterial spectrum, good oral absorbability and long plasma half-life, a series of oxyimino aminothiazolyl 3-{(E)- or (Z)-N-substituted carbamoyloxy}propenyl cephems was synthesized and evaluated for antibacterial activity and oral absorbability . The substituents of the carbamoyloxy group affected their in vitro activity and bioavailability after oral administration of their pivaloyloxymethyl esters at the C-4 position . The compound possessing an N,N-dimethylcarbamoyloxy moiety at the C-3 position showed good oral absorption and well-balanced antibacterial activity . In this report, the structure-activity relationships and the structure-oral absorbability relationships of 3-(N-substituted carbamoyloxy)-propenyl cephems are described.

J Antibiot (Tokyo), 1994 Dec, 47(12), 1507 - 25
Studies on orally active cephalosporins . I . Synthesis and structure-activity relationships of new 3-substituted carbamoyloxymethyl cephalosporins; Negi S et al.; The synthesis and antibacterial activities of 7 beta-{2-(2-aminothiazol-4-yl)-2-hydroxyiminoacetamido}-3-N,N - dimethylcarbamoyloxymethyl-3-cephem-4-carboxylic acid (E1100) and its analogs are described, as well as oral absorbability and in vivo activities of the 1-(isopropoxycarbonyloxy)ethyl ester (E1101) and its analogous esters . The introduction of acyclic and cyclic lower alkyl groups at the N-position of 3-carbamoyloxymethyl cephems influences antibacterial activities, especially against H . influenzae, and oral absorbability of their prodrug esters . The structure-activity relationships are also discussed.

J Antibiot (Tokyo), 1994 Dec, 47(12), 1425 - 33
Spectomycins, new antibacterial compounds produced by Streptomyces spectabilis: isolation, structures, and biosynthesis; Staley AL et al.; Three new tetrahydroanthracene antibiotics have been isolated from modified culture broths of Streptomyces spectabilis . The new compounds, spectomycins A1, A2 and B1, exist as monomeric (C20H20O7, A1; C19H18O7, A2) and as symmetrical dimeric (C38H34O14; B1) forms . Only spectomycin B1 has moderate activity against Gram-positive microorganisms . We report here the structure elucidation and biosynthetic origin of these compounds.

Pharmazie, 1994 Dec, 49(12), 884 - 9
Synthesis, structures and biological activity of some 4-amino-3-cinnolinecarboxylic acid derivatives, Part 1; Stanczak A et al.; This work describes the synthesis of 4-amino-3-cinnolinecarboxamides, which were then hydrolyzed to corresponding 4-amino-3-cinnolinecarboxylic acids . Several compounds were tested for their antibacterial and antifungal activity, and for the central nervous system effect.

Bioorg Med Chem, 1994 Dec, 2(12), 1417 - 21
Structurally designed novel furogamma lactams as inhibitors for bacterial propagations; Ray JK et al.; Some novel furogamma lactams have been synthesised by one step condensation of arylaminomalonates with substituted furyl acryloyl chlorides . The annulation of substituted monocyclic gammalactams followed by cyclization produced novel tricyclic furogamma lactams . Some of these furogammalactams are found to exhibit Gram-positive and Gram-negative antibacterial activity at very high concentrations.

J Cardiovasc Surg (Torino), 1994 Dec, 35(6 Suppl 1), 211 - 7
The management of soft tissue complications related to pacemaker implantations; Har-Shai Y et al.; During the last six years (1988-1993) we have treated 15 patients suffering from soft tissue problems related to pacemaker implantations which included: skin erosions (2 patients), impending extrusion of the pacemaker pulse generator due to capsular contracture (4 patients), exposed pacemaker generator (6 patients), and exposed electrode (3 patients) . This article describes a conservative approach to the treatment of these complications . Skin erosions are treated topically with antibacterial creams or solutions . Local infection is controlled by the administration of systemic antibiotics according to the antibiogram, as well as with local antibacterial dressings . Impending extrusion or exposure of the pacing system are treated by subcapsular relocation of the pacemaker generator or vertical-to-horizontal transposition of the exteriorized lead . These restricted local surgical interventions are designed to overcome the vertical force which tends to cause the extrusion of pacing hardware without using another implantation site which are already limited in number . This approach, which can be repeated, prevents the reintroduction of a new pacing system . The pre-operative evaluation, surgical techniques and a long term follow-up are presented.

Antibiot Khimioter, 1994 Dec, 39(12), 27 - 30
{Chemotherapeutic effectiveness of pefloxacin in experimental infections}; Lobuseva AN et al.; High efficacy of pefloxacin was shown in its study on albino mice with experimental infections such as sepsis, pneumonia and peritonitis . In the effective doses administered orally the drug rapidly arrested the clinical signs of the diseases and provided the sanation of the organs and tissues . The broad antibacterial spectrum of pefloxacin substantiated its efficacy in the treatment of purulent septic processes due to gram-negative and gram-positive pathogens, as well as in the treatment of mixed infections . It is a drug with prolonged action which was confirmed with its prophylactic use . Pefloxacin was efficient in the treatment of infections of various severity.

J Antimicrob Chemother, 1994 Dec, 34(6), 1041 - 5
A comparison of the accumulation of novobiocin into bacteria with its antibacterial properties; Barrett-Bee K et al.; The accumulation of novobiocin in bacteria has been compared with the MIC, inhibition of DNA biosynthesis and inhibition of the activity of isolated DNA gyrase for a range of species . There was a good correlation between MIC and the inhibition of DNA biosynthesis and DNA gyrase . Novobiocin accumulation did not correlate with any other parameter.

Aust Vet J, 1994 Dec, 71(12), 418 - 22
Prevalence of proliferative enteritis on pig farms in Australia; Holyoake PK et al.; Three surveys, undertaken to assess the prevalence of proliferative enteritis (PE) on pig farms in Australia and to investigate risk factors associated with clinical disease, indicated that PE was a common disease in pig farms . Forty of the 71 (56%) randomly-selected producers had either observed PE or had a veterinarian diagnose the disease in their herd during 1988 to 1990 . A relatively low prevalence of the disease was recorded at veterinary diagnostic laboratories, and this suggested that diagnoses of PE were often not confirmed by histopathological examination of the intestines of affected pigs . Non-haemorrhagic PE occurred most often in six- to 24-week-old pigs, but was also reported in 52-week-old pigs . Proliferative haemorrhagic enteropathy usually affected pigs over 16 weeks of age, but was also reported in pigs as young as six weeks and as old as four years of age . A survey of pig-specialist veterinarians indicated that most veterinarians diagnosed PE based on clinical and gross pathological examination of affected pigs, without laboratory confirmation . There were difficulties associated with measuring the prevalence of PE among herds, including the effectiveness of antibacterials for its prevention and control, its subclinical nature and probable mis-diagnoses . This study highlighted the need for an ante-mortem diagnostic test to measure the prevalence of PE more accurately.

Aust Vet J, 1994 Dec, 71(12), 397 - 9
Programs for surveillance and monitoring of antibacterial residues in Australia, 1989 to 1993; Nicholls TJ et al.; The development of a State-based confirmatory testing capability for antibiotic residues in meat in Australia has allowed the rapid feedback to producers failing to comply with antibiotic maximum residue limits . The identification of problem areas in various categories of livestock, and subsequent focused surveillance programs, has reduced the prevalence of antibacterial residues in both domestic and export meat products . Failure to observe withholding periods of antibacterial drugs after treatment is the most significant cause of non-compliance . In the period July 1991 to June 1993 the compliance rate for antibacterial residues for all species was 99.9%.

Eur J Epidemiol, 1994 Dec, 10(6), 703 - 6
Diagnosis of bronchopulmonary infections by quantification of microflora; Pirali F et al.; The quantification of bacteria and fungi in sputum or bronchoaspirate is of clinical value for the diagnosis of respiratory tract infections . We have developed an easy method to count the micro-organisms in patients with respiratory tract infections . This consists of the quantification of micro-organisms by subsequent streakings of a calibrated loop on agar . The correlation between microbiological quantitative data and the clinical status of patients with lower respiratory tract infections is discussed . The data seem to indicate that certain bacteria present in sputum or bronchoaspirate above a certain concentration may be responsible for lower respiratory tract infections . In patients with immunological disorders or chronic pathologies even lower concentrations of micro-organisms in bronchial secretions probably are enough to cause infections . The advantage of this counting method of the microbic species from the respiratory tract consists of their quantification: thus we can attribute an etiological role to a high concentration of the germs, while micro-organisms at low concentrations are probably contaminants . By this method isolated colonies are obtained after 12-18 hours . The bacterial quantification, by respiratory samples examination of the same patient in the following days, allows us to evaluate the efficacy of antibacterial therapy, producing a reduction of bacterial concentration.

J Antibiot (Tokyo), 1994 Dec, 47(12), 1402 - 5
Cepacidine A, a novel antifungal antibiotic produced by Pseudomonas cepacia . I . Taxonomy, production, isolation and biological activity; Lee CH et al.; Cepacidine A is a potent antifungal antibiotic produced by Pseudomonas cepacia AF 2001 . The compound was isolated from the fermentation broth with 1 vol isopropyl alcohol, followed by the collection of the precipitation formed upon concentration of the extract . Purification was effected by chromatography on Diaion HP-20, alumina and reversed phase C18 followed by TLC on silica gel . These techniques afforded the two closely related compounds, cepacidine A1 and cepacidine A2 . A mixture of these two compounds called capacidine A, showed high in vitro antifungal activity against the various animal and plant pathogenic fungi . The activity was diminished by the presence of serum . No antibacterial activity was demonstrable.

J Med Chem, 1994 Nov 25, 37(24), 4195 - 210
7-azetidinylquinolones as antibacterial agents . 2 . Synthesis and biological activity of 7-(2,3-disubstituted-1-azetidinyl)-4-oxoquinoline- and -1,8-naphthyridine-3-carboxylic acids . Properties and structure-activity relationships of quinolones with an azetidine moiety; Frigola J et al.; A series of 7-(2,3-disubstituted-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 study the effects on potency and physicochemical properties of the substituent at position 2 of the azetidine moiety . The activity of the title compounds was determined in vitro against Gram-positive and Gram-negative bacteria, and the in vivo efficacy of selected derivatives was determined using a mouse infection model . The X-ray crystal structures of 6b, 6c, and 6d were found to be in reasonable agreement with the corresponding AM1 calculated geometries . Correlations between antibacterial potency of all the synthesized 7-azetidinylquinolones and naphthyridines and their calculated electronic properties and experimental capacity factors were established . Antibacterial efficacy and pharmacokinetic and physicochemical properties of selected derivatives were compared to the relevant 7-(3-amino-1-azetidinyl) and 7-(3-amino-3-methyl-1-azetidinyl) analogues (for Part 1, see: J . Med . Chem . 1993, 36, 801-810) . A combination of a cyclopropyl or a substituted phenyl group at N-1 and a trans-3-amino-2-methyl-1-azetidinyl group at C-7 conferred the best overall antibacterial, pharmacokinetic, and physicochemical properties to the azetidinylquinolones studied.

J Biol Chem, 1994 Nov 18, 269(46), 28569 - 75
Acute transcriptional response of the honeybee peptide-antibiotics gene repertoire and required post-translational conversion of the precursor structures; Casteels-Josson K et al.; The cell-free immune repertoire of honeybees (Apis mellifera) consists of four polypeptides that are induced by bacterial infection and, through complementarity, provide broad-spectrum antibacterial defense . apidaecin is overproduced by a combination of low threshold transcriptional activation and a unique, genetically encoded amplification mechanism . In contrast, sizable experimental infections are required for induction of the normally silent hymenoptaecin, abaecin, and bee defensin genes; even so, bee defensin transcription is minimal and delayed, and only minute quantities of corresponding peptide are produced . The specific, temporal organization of the multi-component immune response in bees has therefore likely been selected to cope with infection of prevalent, plant-associated Gram-negative bacteria . Post-translational processing and modifications are substantially different for each of the four antibacterial peptides . While no similarities were observed among precursor structures of the various bee peptides, surprisingly, the signal sequences of abaecin (bee) and drosocin (Drosophila) shared unmistakable homology, possibly indicating common ancestral secretion/processing mechanisms . Finally, we report that bee defensin contains a typical disulfide-rich structure (40 amino acids) but also a unique, amphipathic, putatively amidated carboxyl-terminal tail (10 amino acids) . We speculate that this structure is a "co-drug," assembled by fusing "disulfide-rich" and "alpha-helical" class peptide antibiotics, a novel concept in naturally occurring antibacterials.

J Antibiot (Tokyo), 1994 Nov, 47(11), 1188 - 94
Caloporoside, a new inhibitor of phospholipases C from Caloporus dichrous (Fr.) Ryv; Weber W et al.; A new salicylic acid derivative, caloporoside, was isolated from fermentations of Caloporus dichrous . Its structure was elucidated by a combination of chemical and spectroscopic methods . Caloporoside exhibits weak antibacterial and antifungal activities and is a quite selective inhibitor of phospholipase C isolated from pig brain (Ki 12, 3 microM).

J Pharm Sci, 1994 Nov, 83(11), 1617 - 21
Stability determination of 3-bromo-2-hydroxy-N-(3,4-dimethyl-5-isoxazolyl)- 1,4-naphthoquinon-4-imine in ethanol by first-derivative spectrophotometry; Dabbene VG et al.; The degradation kinetics of a new potential tripanocidal and antibacterial agent, 3-bromo-2-hydroxy-N-(3,4-dimethyl-5-isoxazolyl)-1,4- naphthoquinon-4-imine (2), in 95% ethanol, was investigated between 35 and 50 degrees C under room-light and light-protected conditions . The decomposition product was isolated and identified as 2-hydroxy-N-(3,4-dimethyl- 5-isoxazolyl)-1,4-naphthoquinon-4-imine (1) . A simple, rapid, and stability-indicating method for the determination of 2 in the presence of 1 using "zero crossing" first-derivative spectrophotometry is reported . The validity of this method was proved using synthetic mixtures of the intact drug with its decomposition product and by statistical analysis of the calibration data . Pseudo-first-order constants for the degradation reaction of 2, obtained from linear plots of the residual concentration logarithms vs time, the calculated activation parameters Ea, delta H not equal to, and delta S not equal to were similar under room-light and light-protected conditions . The in vitro antibacterial activity of 2 was also evaluated.

J Microencapsul, 1994 Nov-Dec, 11(6), 657 - 62
Effect of encapsulation of chloramphenicol in albumin microspheres on its in vitro transfer across the human placenta; Onur MA et al.; The possibility of reducing drug transfer across the placenta was tested in two of our previous studies . The aim of those studies was to demonstrate an alternative method of drug application during pregnancy which we think would yield a dual benefit, i.e . protecting the foetus from the harmful effects of drugs while curing the mother . The present study was planned as a continuation of the testing of the same idea and we tried to see the effect of albumin microsphere encapsulation of chloramphenicol on its transfer across the human placenta in vitro . Microspheres containing chloramphenicol were prepared according to the method previously described . The mean per cent encapsulation of chloramphenicol in albumin microspheres was found to be 42 +/- 4.3 per cent (n = 5) and the mean size of the albumin microspheres was 3.08 +/- 0.6 mm . In vitro stability of the drug-carrying microspheres was measured by dialysing them at 37 degrees C for 24 h . Chloramphenicol was released from the microspheres gradually leaving about 50 per cent of the entrapped drug in the microspheres after 1.5 h . About 20 per cent of the chloramphenicol was retained in the microspheres at 24 h postincubation . The persistence of the antibacterial effect of the released chloramphenicol is confirmed by antibiogramme tests . In the perfusions the initial free drug concentration was kept at 100 mg/ml.(ABSTRACT TRUNCATED AT 250 WORDS)

Boll Chim Farm, 1994 Nov, 133(10), 662 - 4
Antibacterial evaluation of some xanthate derivatives and their diorganotin (IV) complexes; Rashan LJ et al.; The antibacterial activity of some xanthate derivatives K(SSCOR), where R = C6H5-(CyX), CH3NHCH2CH2-(MAEX), (CH3)2NCH2CH2-(DMAX), (CH3)2NCH2CH(CH3)-(DMAIX) and (C2H5)2NCH2CH2-(DEAEX) together with their diorganotin (IV) complexes R2Sn(SSCOR)2, where R' = Me, Bu(n), Ph, has been studied against eight species of bacteria in vitro . A significant activity against S . typhimurium was displayed by the xanthate derivative CyX and its complex Ph2Sn(CyX)2 at concentrations ranging from 1-10 micrograms/ml, and a remarkable activity was exhibited by the complexes Ph2Sn(CyX)2, Ph2Sn(MAEX)2 and Ph2Sn(DMAX)2 against P . aeruginosa at concentrations ranging from 0.1-10 micrograms/ml . By contrast, no such activity was demonstrated by the antibiotics used in this study (amoxicillin and chloramphenicol) against the same bacterial species.

Chem Pharm Bull (Tokyo), 1994 Nov, 42(11), 2269 - 75
Studies on chemical modification of monensin . V . Synthesis, sodium ion permeability, antibacterial activity, and crystal structure of 7-O-(4-substituted benzyl)monensins; Nagatsu A et al.; 7-O-(4-Substituted benzyl)monensins (3a-g) were synthesized from monensin (1), and their lipophilicity, antibacterial activity, and Na+ ion permeability were examined . 7-O-(4-Ethylbenzyl)monensin (3e) showed the largest Na+ ion permeability, but 3c,f,g showed smaller Na+ ion permeability than 7-O-benzylmonensin (2) in spite of higher lipophilicity . An X-ray study of the sodium salt of 3e revealed that the benzyl group was located over the position between the D and E rings, and that the ethyl substituent on the benzyl group was close to the C(28) methyl group on the E ring.

J Nat Prod, 1994 Nov, 57(11), 1606 - 9
Antibacterial and antifungal sulfated alkane and alkenes from the hepatopancreas of the ascidian Halocynthia roretzi; Tsukamoto S et al.; Four new antibacterial and antifungal sulfates, 2,6-dimethylheptyl sulfate {1}, (4Z,7Z)-4,7-decadienyl sulfate {2}, (4Z,7E)-4,7-decadienyl sulfate {3}, and (3Z,6Z)-3,6,9-decatrienyl sulfate {4}, have been isolated from the hepatopancreas of the ascidian Halocynthia roretzi . The structures were determined by spectral analysis.

J Clin Periodontol, 1994 Nov, 21(10), 717 - 9
Triclosan protects the skin against dermatitis caused by sodium lauryl sulphate exposure; Barkvoll P et al.; It has recently been suggested that the lipid-soluble, antibacterial agent triclosan possesses an anti-inflammatory effect in the oral cavity . The aim of the present study was to examine whether triclosan can protect the skin from the irritation or inflammation that may be caused by exposure to sodium lauryl sulphate (SLS) . Finn Chamber patch tests on the forearms of 10 volunteers showed that a mixture of SLS and triclosan caused no inflammation, whereas SLS alone caused reactions in all the subjects . Pre-treatment with triclosan before SLS exposure had a slight effect whereas treatment after exposure showed a significant effect . It is suspected that the reported anti-gingivitis effect of triclosan may at least in part be explained by an anti-inflammatory effect.

Arzneimittelforschung, 1994 Nov, 44(11), 1265 - 8
In vitro clastogenicity of optical isomers of nadifloxacin; Takahashi N et al.; The potential of optical isomers of the fluoroquinolone antibacterial agent nadifloxacin (NDFX, CAS 124858-35-1) to induce chromosomal aberrations in vitro was investigated in cultured Chinese hamster lung (CHL) cells for 24 h of continuous treatment . S- and R-enantiomers of NDFX showed significant differences in the results of the chromosomal aberration test, but no marked differences in the results of cytotoxicity test, i.e., S-NDFX induced chromosomal aberrations, but R-NDFX did not . These results were equivalent to those obtained with ofloxacin (OFLX, CAS 83380-47-6), which has a chemical structure similar to that of NDFX . Moreover, although neither NDFX nor OFLX induced aberrations, their mixtures, prepared from equal amounts of S- and R-enantiomers, did . This finding suggests that the racemic compound and the mixture of S- and R-enantiomers exist under different conditions within the solution.

Plant Physiol, 1994 Nov, 106(3), 977 - 81
Expression of a human lactoferrin cDNA in tobacco cells produces antibacterial protein(s); Mitra A et al.; A suspension tobacco (Nicotiana tabacum L.) cell line was transformed to express human lactoferrin, an iron-binding glycoprotein . The transgenic calli produced a protein that was significantly smaller than the full-length lactoferrin protein . Total protein extracts made from transgenic tobacco callus exhibited much higher antibacterial activity than commercially available purified lactoferrin as determined by the decrease of colony-forming units when tested with four phytopathogenic species of bacteria . Introduction of the lactoferrin gene in crop plants may provide resistance against phytopathogenic bacteria.

Br J Gen Pract, 1994 Nov, 44(388), 509 - 13
Repeat consultations after antibiotic prescribing for respiratory infection: a study in one general practice; Davey P et al.; BACKGROUND . Several new antibacterial drugs have been introduced in the last 10 years with the aim of improved treatment of respiratory tract infection . AIM . The study set out to use repeat consultations as a measure of the outcome of antibiotic treatment for respiratory tract infection, and to develop a simple model for discussion of the cost effectiveness of alternative antibiotic treatments . METHOD . All consultations to one practice during a single winter were reviewed by one general practitioner . RESULTS . A total of 1140 patients had acute symptoms suggestive of respiratory infection . Of these, 899 patients (79%) were prescribed antibiotics at the first consultation and 160 of the 899 patients (18%) returned for one or more repeat consultations; only nine repeat consultations were due to adverse effects of the antibiotics prescribed . Only two patients were admitted to hospital for respiratory symptoms following initial antibiotic therapy and both patients had additional reasons for their admission . Using the highest estimates, the cost of a repeat consultation was found to be 28.54 pounds . These data were used to calculate how much more might be spent on more effective antibiotics at the first consultation . It would be difficult to justify increasing the cost of antibiotic treatment by more than 5 pounds per patient, even if the new treatment were 100% effective and all repeat consultations were due to treatment failure (5 pounds is equal to 28.54 pounds x 0.18, which is the maximum cost of a repeat consultation multiplied by the proportion of patients prescribed antibiotics who make repeat consultations) . CONCLUSION . From these results and a review of the literature it can be concluded that new antibacterial drugs will have to be carefully targeted if they are to prove cost effective in practice . Other methods for reducing repeat consultation merit investigation.

Antibiot Khimioter, 1994 Nov, 39(11), 3 - 9
{Metabolic transformation of antibiotics of the tetracycline series in peroxidase reactions}; Petrenko IuM et al.; In was shown calorimetrically that in the presence of horse radish peroxidase tetracyclines induced degradation of hydrogen peroxide . Under such conditions changes in the tetracycline optical properties were detected photometrically . It was concluded that tetracyclines were metabolized in the peroxidase reactions catalyzed by horse radish peroxidase as their substrates . The tetracycline peroxidase oxidation was catalyzed not only by horse radish peroxidase but also by methemoglobin possessing the peroxidase activity . In the experiments with ascorbate there were detected characteristic peculiarities of the tetracycline peroxidase oxidation catalyzed by both horse radish peroxidase and methemoglobin . These peculiarities made it possible to classify the tetracyclines as the substrates of the peroxidase reaction belonging to the oxidogenic group . The fact that tetracyclines can be metabolized in peroxidase reactions is discussed in regard to its possible influence on their mechanism of antibacterial action and the development of tetracycline resistance.

Khirurgiia (Mosk), 1994 Nov, (11), 22 - 6
{Treatment of diffuse peritonitis}; Nikhinson RA et al.; From study of the values of central and peripheral hemodynamics in 369 patients with peritonitis of the diffuse form, it may be concluded that they reflect objectively the degree of intoxication . A hypodynamic reaction of the blood-vascular system is a poor prognostic sign indicative of progressing peritonitis . Much significance is attached to morphological and microbiological study of the biopsy material of the parietal peritoneum, which allows judgement of the stage of peritonitis . Along with the traditional infusion and antibacterial therapy in peritonitis, UVI of autoblood and intravenous laser irradiation of the blood in stages IIA and IIB are applied . This should be followed by hemosorption which contributes to the active excretion of toxins from the organism . The authors recommend the method of programmed relaparotomy in stage IIB when there is a large amount of exudate with a collibacillary odour and a tendency to the formation of unterintestinal abscesses . Intraaortal infusion of medicinal agents is recommended in this clinical group marked by a tendency towards hypotension . In the group of 369 patients who underwent operation 112 (29.5%) died.

Clin Ther, 1994 Nov-Dec, 16(6), 989 - 99
Effect of intravenous administration of EM523L on gastric emptying and plasma glucose levels after a meal in patients with diabetic gastroparesis: a pilot study; Nakamura T et al.; EM523L, a newly developed erythromycin derivative, has a powerful motilin-like biologic effect and no antibacterial activity . In this pilot study, EM523L was administered to six patients with diabetic gastroparesis, and its effects on gastric emptying function and the change in plasma glucose levels after eating were examined . Gastric emptying was evaluated by the simultaneous measurement of solid and liquid food intake using 99mTc-Sn-colloid and acetaminophen, respectively . Eggs labeled with isotope and milk with added acetaminophen were used as the test meals . The change in plasma glucose level after ingestion of the test meal was also examined . A total of 2 mg of EM523L dissolved in 100 mL of physiologic saline was administered by intravenous infusion over a period of 15 minutes after ingestion of the test meal . The retention rates of the gastric isotope decreased following the administration of EM523L at 20 to 120 minutes after ingestion of the test meal . Plasma acetaminophen concentrations following EM523L administration increased at 20 and 30 minutes . The plasma glucose levels showed an increase at 30 to 60 minutes after eating--the result of improved gastric emptying function . From these results, we concluded that intravenous administration of EM523L in patients with severe diabetic gastroparesis promotes gastric emptying of a solid and liquid meal and, as a result, plasma glucose levels increase after eating.

FEBS Lett, 1994 Oct 31, 354(1), 97 - 102
Pore-forming peptide of Entamoeba histolytica . Significance of positively charged amino acid residues for its mode of action; Andra J et al.; Amoebapore is a 77-residue pore-forming peptide from Entamoeba histolytica with antibacterial and cytolytic properties . It contains eight lysine residues and one histidine residue . Chemical modifications of amoebapore with various reagents affecting either both types of cationic residues or lysine and histidine residues separately resulted in virtually complete loss of pore-forming activity . The activity was restored by reversal of modifications . Whereas amoebapore was no longer capable of binding to phospholipid vesicles when its lysine residues were modified, the modification of the single histidine primarily affected oligomerization of the peptide upon membrane association.

J Biol Chem, 1994 Oct 21, 269(42), 26338 - 43
Determinants of the inhibitory action of purified 14-kDa phospholipases A2 on cell-free prothrombinase complex; Inada M et al.; It has been suggested (Kini, R . R., and Evans, H . J . (1987) J . Biol . Chem . 262, 14402-14407) that the anticoagulant activity of members of the 14-kDa phospholipase A2 (PLA2) family depends on the presence of basic residues within a variable surface region (residues 54-77) distinct from both the conserved catalytic machinery and surface sites mediating the antibacterial action of these enzymes (see Weiss, J., Inada, M., Elsbach, P., and Crowl, R . M . (1994) J . Biol . Chem . 269, 26331-26337) . To further define the determinants of the anticoagulant activity of PLA2, we have analyzed the inhibitory effects of purified native and recombinant PLA2 on cell-free prothrombinase . Both native and recombinant wild-type pig pancreas (net charge -1) and human "secretory" PLA2 (net charge +15) produced similar dose-dependent inhibition of prothrombinase activity that was significantly less potent than a toxic PLA2 purified from snake venom . Site-specific mutations that either increased or decreased PLA2 activity toward bactericidal/permeability-increasing protein-treated Escherichia coli by up to 50-fold had no effect on antiprothrombinase activity . In contrast, substitution of Arg for Asp-59/Gly for Ser-60 in the pig PLA2 increased antiprothrombinase activity by 5-10-fold without affecting catalytic activity toward a range of phospholipid substrates or antibacterial activity . Comparison of antiprothrombinase activity of catalytically active and inactive forms of the PLA2 and under a range of phospholipid conditions revealed that the potent antiprothrombinase activity of native toxic venom PLA2 and of the D59R.S60G mutant pancreatic PLA2 reflect combined catalytic and noncatalytic actions, the latter apparently dependent on basic residues at discrete surface sites in the enzyme.

Planta Med, 1994 Oct, 60(5), 455 - 9
Isolation of bis-indole alkaloids with antileishmanial and antibacterial activities from Peschiera van heurkii (syn . Tabernaemontana van heurkii); Munoz V et al.; Extracts from leaves and stem bark of Peschiera van heurkii (Muell . Arg.) L . Allorge (syn . Tabernaemontana van heurkii Muell . Arg., Apocynaceae) have been assayed for antileishmanial and antibacterial activities . The activities were concentrated in the alkaloid fractions which yielded 20 indole and bisindole alkaloids . The strongest leishmanicidal and antibacterial activities were observed with the dimeric alkaloids conodurine (1), N-demethylconodurine (= gabunine) (2), and conoduramine (3) . Weak toxicity towards macrophage host cells and strong activity against the intracellular amastigote form of Leishmania were observed for compounds 1 and 2 . In vivo, 1 was less active than glucantime (= N-methylglucamine antimonate), the drug of reference, while 2 was devoid of activity at 100 mg/kg.

Appl Environ Microbiol, 1994 Oct, 60(10), 3566 - 72
In vivo monitoring system for structure-function relationship analysis of the antibacterial peptide apidaecin; Taguchi S et al.; A unique antibacterial peptide derivative found in immune honeybee lymph, apidaecin 1b (AP1), was randomly mutagenized and characterized by a newly established system to analyze in vivo its structure-function relationship . Initially, a high-level expression host-vector system for AP1 in Escherichia coli was constructed by creating a fusion protein with the highly stable Streptomyces subtilisin inhibitor (SSI) molecule . Expression of the SSI-AP1 fusion protein was found to depend on the concentration of the transcriptional inducer isopropyl-beta-D-thio-galactopyranoside (IPTG) and to parallel the degree of growth inhibition of the transformant cells . Subsequently, apidaecin derivatives produced by localized random mutagenesis were screened with this IPTG concentration-controlled in vivo system by monitoring the growth inhibition patterns of the transformant cells . One mutant apidaecin (P9L) that had reduced activity was purified and isolated from the periplasmic fraction of an E . coli transformant . Its antibacterial activity was reduced to one-third of that of wild-type apidaecin . When considered together with the other mutations, it was concluded that several Pro residues, including that at the ninth position, are responsible for expression of the antibacterial action of apidaecin.

Gut, 1994 Oct, 35(10), 1385 - 8
Low prevalence of Helicobacter pylori in inflammatory bowel disease: association with sulphasalazine; el-Omar E et al.; The prevalence of IgG antibodies to Helicobacter pylori was examined in 110 patients with inflammatory bowel disease (IBD) (63 ulcerative colitis, 47 Crohn's disease) and compared with 100 age and sex matched control patients . The overall prevalence of H pylori seropositivity in the IBD patients was 22%, which was significantly less than that of 52% in the controls (p < 0.002) . There was no difference in prevalence between ulcerative colitis and Crohn's patients . The low seropositivity in the IBD patients resulted from a very low prevalence of 10% in those currently receiving sulphasalazine (n = 40) and similarly low prevalence of 7% in those previously receiving sulphasalazine (n = 30) . In those receiving olsalazine or mesalazine and who had never had sulphasalazine, the prevalence of seropositivity was 45% . Further studies using 14C urea breath test and microscopy of antral biopsy specimens confirmed that the negative serology in patients receiving sulphasalazine resulted from absence of the infection rather than absence of humoral immune response to it . In six control patients with H pylori infection, a two week course of sulphasalazine (500 mg four times daily) only caused slight suppression of the 14C urea breath test . In vitro studies failed to show any direct antibacterial effect of sulphasalazine on H pylori . These findings indicate that longterm treatment with sulphasalazine leads to eradication of H pylori infection and that this does not result from a direct antibacterial effect . It may be caused by the drug treating the gastritis and thereby depriving the bacterium of essential nutrients exuded by the inflamed mucosa.

J Am Diet Assoc, 1994 Oct, 94(10), 1140 - 4
Preventing infection from foodborne pathogens in liver transplant patients; Cabelof DC; Patients who have had an orthotopic liver transplantation (OLT) experience impaired immune function resulting from the disease process and the therapeutic use of immunosuppressive and antibacterial drugs . Immunoimpairment increases the risk of foodborne illness from bacteria, viruses, fungi, and parasites . This article describes the organisms known to cause clinically important infections and their food sources, the distinctive clinical consequences of the infection in patients who have had an OLT, and methods of preventing foodborne illness in these patients and others . Dietitians are the health care providers typically responsible for teaching OLT patients and their caregivers about safe food handling and appropriate food choices.

Photodermatol Photoimmunol Photomed, 1994 Oct, 10(5), 202 - 5
In vitro phototoxic activities of new quinolone antibacterial agents: lipid peroxidative potentials; Fujita H et al.; To determine the fundamental photochemical properties of new quinolones that can induce photosensitivity, the in vitro phototoxicity of these drugs (enoxacin, norfloxacin, ofloxacin, ciprofloxacin, and lomefloxacin) was examined with respect to photosensitizing ability to peroxidize unsaturated lipid squalene in ethanol solution . Lomefloxacin and ciprofloxacin showed the highest efficiency in sensitization of peroxidation of the lipid . Moderate repression of peroxidation occurred by addition of sodium azide (a quencher of singlet molecular oxygen), suggesting that the nonsinglet oxygen mechanism is operative in addition to the singlet oxygen mechanism.

Trends Microbiol, 1994 Oct, 2(10), 372 - 80
Molecular structures of penicillin-binding proteins and beta-lactamases; Ghuysen JM; In the past, new antibacterial agents have been selected either from natural sources or by 'trial and error' modification of existing antibacterials . Future therapeutic strategies are likely to depend on increased knowledge of existing drug targets and the search for new targets . The machinery for the assembly of bacterial-cell-wall peptidoglycan is an ideal place to look.

Curr Opin Genet Dev, 1994 Oct, 4(5), 672 - 7
Molecular genetics of Drosophila immunity; Ip YT et al.; Insects resist bacterial infections through the induction of both cellular and humoral immune responses . The cellular response involves the mobilization of hemocytes, whereas the humoral response utilizes antibacterial peptides that are synthesized in the fat bodies and secreted into the circulating hemolymph . Recent studies suggest that the induction of the humoral response involves Rel-containing regulatory proteins, Dif and dorsal, which are related to mammalian NF-kappa B . These regulatory proteins function as sequence-specific transcription factors that induce the expression of immunity genes, including cecropin and diptericin . In mammals, NF-kappa B has been implicated in both lymphocyte differentiation and the acute-phase response . The finding that insect and mammalian immunity involve related transcription factors offers the promise that genetic studies in Drosophila might lead to the identification of novel components mediating mammalian immunity.

Antimicrob Agents Chemother, 1994 Oct, 38(10), 2323 - 9
Possible intermolecular interaction between quinolones and biphenylacetic acid inhibits gamma-aminobutyric acid receptor sites; Akahane K et al.; The combination of some new quinolone antibacterial agents with 4-biphenylacetic acid (BPAA), a metabolite of fenbufen, is known to specifically induce functional blockade of the gamma-aminobutyric acid (GABA) receptors . The mechanisms of these drug interactions were further examined . Scatchard analysis of {3H}muscimol binding to rat brain plasma membranes in the presence of enoxacin and BPAA revealed that a significant decrease in the number of muscimol binding sites was produced without affecting the affinity of binding to the receptors . In the presence of norfloxacin, BPAA inhibited muscimol binding the most potently of the six BPAA-related compounds tested . Fenbufen and 9,10-dihydro-gamma-oxo-2-phenanthrenebutyric acid also inhibited the binding, and 4-biphenylcarboxylic acid and methyl 4-biphenylacetate inhibited it slightly, but 3-benzoylpropionic acid exhibited no competitive inhibition . Accordingly, hybrid molecules of norfloxacin and BPAA were synthesized for stereochemical analysis of these drug interactions . A hybrid with a -CONH(CH2)3- chain between norfloxacin and BPAA (flexible structure) inhibited muscimol binding, and intracisternal injection of this hybrid caused clonic convulsions in mice more potently than the combination of norfloxacin and BPAA did . In contrast, a hybrid linked by -CONH- (stretched structure) showed almost no such inhibitory effect . 1H NMR analysis indicated the presence of intramolecular attraction at the quinoline ring of the hybrid exhibiting the antagonistic activity . These results suggest the possibility that quinolones and BPAA interact with the GABA receptor at nearby sites and that the binding affinity of quinolones to the GABA receptors is largely enhanced by the intermolecular interaction with BPAA.

Farmaco, 1994 Oct, 49(10), 675 - 7
Antibacterial activity of N-phenylmaleimides, N-phenylsuccinimides and related compounds . Structure-activity relationships; Cechinel Filho V et al.; The antibacterial activity of several phyllanthimide analogs were investigated by the Minimum Inhibitory Concentration Method (MIC) against E . coli and S . aureus . It was found that maleimides were approximately 30 times more active than succinimides indicating that the cyclic imido double bond is an important factor related to the activity . Electron-donor and electron-withdrawing substituents in the aromatic ring of N-phenylmaleimides decrease the activity of these compounds indicating the possibility of steric effects . The distance between the aromatic and the imido rings when separated by methylene groups does not affect the antibacterial activity.

Farmaco, 1994 Oct, 49(10), 671 - 4
New heterocyclic derivatives of benzimidazole with germicidal activity--XI--Experimental validation of OSAR prediction on antibacterial and antimycotic activity of benzimidazole derivatives; Pedini M et al.; In continuation of previous studies, Authors describe the synthesis of three new derivatives of 2-(5'-nitro-2'-furyl) benzimidazole, having hydroxy, methoxy or amino group at position 5 . The new compounds, synthesized as suggested by a previous chemometric study, were tested in vitro against 5 Gram + and 4 Gram- strains and the mycete C . albicans . Two derivatives (R = OH, NH2) showed a good degree of antibacterial activity, especially the 5-hydroxy derivative, but they were practically inactive against the mycete; these results are in agreement with the prediction of chemometric study.

East Afr Med J, 1994 Oct, 71(10), 628 - 30
Antibiotic residues in milk received by dairy cooperative societies in Kiambu district, Kenya; Ombui JN; A survey of antibiotic inhibitors in milk received by dairy cooperative societies in Kiambu district was done qualitatively using microbiological assay method . No antibacterial inhibitors were detected in all the samples tested . Informal discussions indicated a high level of awareness of the withdrawal requirement of veterinary drugs after animal treatment in both farmers and the management staff of dairy cooperative societies . The results show that milk from this area is free of antibiotic residues and farmers could be adhering to the withdrawal requirement of veterinary drugs . Such milk therefore does not pose a risk to the public and dairy industry.

Br J Surg, 1994 Oct, 81(10), 1423 - 9
Macrolides in roles beyond antibiotic therapy; Pilot MA; Erythromycin and other macrolides with a closely related structure are widely used antibiotics . Side-effects related to administration of such drugs are mostly gastrointestinal . The direct effect of erythromycin on gastrointestinal motility was studied; it was found to have a stimulatory effect proximally, on stomach and duodenal motility, with an apparent distal inhibition . Gastric emptying was accelerated by erythromycin via an antroduodenal coordination mechanism, an effect that has proved to be beneficial in surgical and medical conditions in which gastroparesis is a problem . Erythromycin is now used experimentally and clinically; it has been found to accelerate gastric as well as gallbladder emptying and to have an effect on the oesophagus . Analogues of erythromycin have been developed that have potent gastrointestinal activity but little or no antibacterial potential . Macrolides modulate the antibacterial action of neutrophils, with some action on the oxidative burst . Finally, two new macrolide immunosuppressants have been developed that compare favourably with traditional drugs.

Scand J Dent Res, 1994 Oct, 102(5), 306 - 8
Organic solvents and oils as vehicles for triclosan in mouthrinses: a clinical study; Kjaerheim V et al.; Previous experiments have shown that the nature of the detergents used in aqueous triclosan-containing mouthrinses affects the plaque-inhibiting effect of these mouthrinses, probably because of the properties of the micelles formed . It has also been shown that triclosan has a marked plaque-inhibiting effect when dissolved in pure propylene glycol . The aim of the present study was to compare the clinical effect of triclosan dissolved in oils and in the pure solvents glycerol (GLY) and polyethylene glycol (PEG) . A test panel of 12 volunteers rinsed with the allocated mouthrinses for 4 days in a double-blind, crossover study . Three different oils were tested: olive oil, soy oil, and sunflower seed oil, as well as PEG and GLY . Triclosan was used in a 0.3% concentration to facilitate comparison with previous studies . However, only 0.15% triclosan was added to the GLY-containing rinse (maximum soluble concentration) . In addition, soy oil without triclosan was tried . The mean plaque score for water was 1.42 +/- 0.19; for olive oil, 1.08 +/- 0.34; for soy oil with triclosan, 0.95 +/- 0.35; for pure soy oil, 0.94 +/- 0.09; for sunflower seed oil, 1.19 +/- 0.19; for PEG, 1.04 +/- 0.22; and for GLY, 1.12 +/- 0.28 . The results indicate that triclosan dissolved in oils loses its clinical effect . However, oils in themselves exhibit significant plaque inhibition . In vitro tests showed no antibacterial activity of triclosan dissolved in oils . Toothpastes and mouthrinses contain flavoring oils and occasionally also GLY and PEG . Such substances may well interfere with the clinical effect of triclosan in these products.(ABSTRACT TRUNCATED AT 250 WORDS)

Vnitr Lek, 1994 Oct, 40(10), 676 - 8
{Prophylaxis of infectious endocarditis}; Benes J; In spite of introducing antibacterial agents in prophylaxis of infective endocarditis (I.E.) more than 50 years ago, the optimal scheme for indication and application of the prophylaxis has not been solved . Evidences accumulate that prophylaxis (being developed to cover some medical procedures leading to bacteremia) can prevent only a small part (< 10%) of cases of I.E . The most effective protection from I.E . is the systematic care for gums and mucosae of the mouth cavity.

J Trop Pediatr, 1994 Oct, 40(5), 305 - 7
Vitamin A supplementation in post-measles complications; Madhulika et al.; One-hundred-and-seventy-seven children with post-measles complications divided into two comparable groups were studied for the effect of Vit.A Supplementation . Eighty-nine children received Vit.A in doses of 200,000 units daily on two consecutive days in addition to antibacterials and other supportive care and 88 did not reveice Vit.A . The case fatality rate was 16 per cent in those who received VIT.A, while the same was 32 per cent in those who did not receive Vit.A (P < 0.02) . There was no statistical difference in the mortality rate among two groups when the children were suffering from severe malnutrition or encephalopathy (P > 0.1).

Dent Clin North Am, 1994 Oct, 38(4), 707 - 18
Antibacterial prophylaxis; Hall EH et al.; Bacteremias of dental origin have been implicated as sources of infection in specific cardiac conditions, diabetes, neutropenia, kidney disease, splenectomy, and patients with prosthetic joints . This article reviews the relative risks of dental bacteremias in these patients, discusses the merits of various regimens, and presents current prophylactic antibiotic recommendations.

Chem Pharm Bull (Tokyo), 1994 Oct, 42(10), 2063 - 70
Pyridonecarboxylic acids as antibacterial agents . VIII . Synthesis and structure-activity relationship of 7-(1-aminocyclopropyl)-4-oxo-1,8-naphthyridine-3-carboxylic acids and 7-(1-aminocyclopropyl)-4-oxoquinoline-3-carboxylic acids; Todo Y et al.; 4-Oxo-1,8-naphthyridine- and 4-oxoquinoline-3-carboxylic acids (2a, b and 3a-1) possessing a 1-amino-cyclopropyl group at the 7-position have been synthesized and evaluated for in vitro antibacterial activities . The three quinolones (3d, h, i) exhibited potent antibacterial activities against both gram-positive and gram-negative bacteria, which are comparable to those of ciprofloxacin (CPFX) and ofloxacin (OFLX) . Among the three compounds, the best pharmacological and pharmacokinetic profile was obtained with 3i, an OFLX analogue, which was considerably less toxic than three reference quinolones (1, CPFX and OFLX).

Singapore Med J, 1994 Oct, 35(5), 505 - 8
Chronic granulomatous disease--a report in two Malay families; Mohd Noh L et al.; Chronic granulomatous disease (CGD) is a very rare disease whose defect lies in an abnormal intracellular killing resulting in recurrent abscesses, lymphadenitis and granuloma formation . We describe 2 Malay male infants with CGD whom we believe to be the first report of this disorder in Malays . Both children presented with recurrent abscesses, pneumoniae and hepatosplenomegaly; lymphadenopathy was also present in one of the patients . The organisms isolated were catalase positive bacteria . Both neutrophil chemiluminescence (against fungal and bacterial antigens, phorbol myristate acetate) and intracellular killing assays were severely depressed . Recognition of CGD is important as great strides have been made in the treatment of this disease which include gamma interferon therapy besides the conventional prophylactic antibacterial therapy.

Br J Haematol, 1994 Oct, 88(2), 256 - 60
Serum levels of granulocyte-colony stimulating factor (G-CSF) in bacterial and viral infections, and in atypical pneumonia; Pauksen K et al.; Serum granulocyte-colony stimulating factor (G-CSF) was measured with an ELISA method in patients with acute bacterial and viral infections, or with an atypical pneumonia . Before initiation of antibiotic treatment, G-CSF was found to be significantly increased (799 +/- 1501 ng/l) in sera from 34 patients with an acute bacterial infection compared with the 27 patients with a viral infection (58 +/- 34 ng/l; P < 0.001) and with the eight patients with an atypical pneumonia (60 +/- 33) ng/l; P < 0.001) . No significant difference in G-CSF levels was seen between gram-positive and gram-negative bacterial infections . In septic shock, increased G-CSF levels were seen both in patients with leucocytosis and leucopenia . In uncomplicated bacterial infections, both G-CSF and IL-6 were increased on day 0, and decreased rapidly after initiation of antibacterial therapy and before the patients became afebrile . In bacterial infections on day 0, G-CSF levels correlated with mononuclear cells (rs = -0.62, P < 0.001), IL-6 (rs = 0.40, P < 0.05) and S-MPO (rs = -0.5, P < 0.01) . In viral infections, G-CSF was correlated with mononuclear cells (rs = 0.41, P < 0.05), white blood cell counts (rs = 0.56, P < 0.01), neutrophils (rs = 0.41, P < 0.05) and CRP (rs = 0.47, P < 0.05) . We conclude that G-CSF is rapidly raised in the blood in acute bacterial infections but not in acute viral infections or in infections with Mycoplasma pneumonia . Our results also support the theory that G-CSF is involved in the mechanisms of mobilization of neutrophils into the peripheral circulation.

J Med Chem, 1994 Sep 30, 37(20), 3344 - 52
(Fluorocyclopropyl)quinolones . 2 . Synthesis and Stereochemical structure-activity relationships of chiral 7-(7-amino-5-azaspiro{2.4}heptan-5-yl)-1-(2-fluorocyclopropyl)quinolone antibacterial agents; Kimura Y et al.; A series of novel chiral 7-(7-amino-5-azaspiro{2.4}heptan-4-yl)-8-chloro-1-(2-fluo rocyclopropyl)- quinolones were synthesized as a continuation of a research project of 1-(2-fluorocyclopropyl)-quinolones by considering stereochemical and physicochemical properties of the molecule . Absolute configurations of the 1-(cis-2-fluorocyclopropyl) moiety and the 7-(7-amino-5-azaspiro-{2.4}heptan-5-yl) moiety were determined by X-ray crystallographic analysis . Stereochemical structure-activity relationship studies indicated that 1-{(1R,2S)-2-fluorocyclopropyl} and 7-{(7S)-amino-5-azaspiro{2.4}heptan-5-yl} derivatives are more potent against Gram-positive and Gram-negative bacteria than the other stereoisomers and 7-{(7S)-7-amino-5-azaspiro{2.4}-heptan-5-yl}-8-chloro-1-{(1R ,2S)-2- fluorocyclopropyl}quinolone (33) is the most potent of all stereoisomers . Pharmacokinetic profiles and physicochemical properties of the selected compounds were also examined, and it was found that 33 (DU-6859a) possesses moderate lipophilicity and good pharmacokinetic profiles.

Presse Med, 1994 Sep 17, 23(27), 1252 - 6
Frequency of infections and their relation to episodes of acute rejection among heart allograft recipients; Lemstrom K et al.; OBJECTIVES: Infections and episodes of acute rejections are major factors affecting allograft survival during the first year after transplantation . The frequency of infections, and the relation of injections to rejection episodes were studied among heart allograft recipients with the follow-up time one year . METHODS: The study population consisted of 58 patients receiving a heart allograft through 1985 to 1990 . Low-dose triple-drug therapy was used for immunosuppression, and rejections were treated either with methylprednisolone, antithymocyte globulin, or the combination of methylprednisolone and antithymocyte globulin . The patients received 2 g of vancomycin i.v . 2 days postoperatively, and no further antibacterial prophylaxis was used . The diagnosis of infection was based on clinical symptoms and on microbiological or serological demonstration of an infection . When the correlations between severe infections and rejections were examined, only infections occurring within 1 month from the onset of the rejection were included . Chi-square test was used for statistical analysis . RESULTS: Seventy-nine infections were registered (1.6 +/- 1.4 episodes/patients); 74% of the patients underwent at least one infection episode . Most infections, 61% (49), occurred during the first three posttransplant months, cytomegalovirus and bacterial agents accounting for the most important aetiology . No difference in the overall infection frequency existed between the patients with or without rejections . Twenty seven infection episodes were recorded in 18/50 patients with rejections (p = NS), 11 of them in relation to rejection in 5/18 patients . The frequency of infections after antirejection therapy either with antithymocyte globulin or the combination of methylprednisolone and antithymocyte globulin (7/11) was higher than with methylprednisolone alone (4/20) (p < 0.05) . Infections were the primary cause of death in 50% . The rest of deaths were caused by acute rejections . CONCLUSION: There was a typical pattern of infections occurring mainly during the first three months after transplantation, and a significant tendency towards severe infections after intense antirejection therapy with antithymocyte globulin.

Eur J Biochem, 1994 Sep 15, 224(3), 1019 - 27
Secondary structure and membrane interaction of PR-39, a Pro+Arg-rich antibacterial peptide; Cabiaux V et al.; PR-39 is a 4719-Da peptide isolated from pig intestine and belonging to the recently discovered family of Pro+Arg-rich antibacterial peptides . PR-39 does not lyse Escherichia coli, instead the lethal action is probably linked to the termination of DNA and protein synthesis {Boman, H . G., Agerberth, B . & Boman, A . (1993) Infect . Immun . 61, 2978-2984} . Circular dichroism and Fourier-transform infrared spectroscopy have been used to investigate the secondary structure of PR-39 in the absence or presence of lipids . According to the circular dichroic data, this structure is not altered upon incubation of PR-39 with negatively charged vesicles, although the infrared spectra suggest that the hydrogen bond pattern is modified upon the peptide-lipid interaction . This is detected by a shift in the maximum wavelength of absorption of PR-39 from 1636 cm-1 in the absence of lipids to 1645 cm-1 in the presence of lipids . We have further addressed the question of the possible mechanism of interaction of PR-39 with model membranes (liposomes and planar lipid bilayers) whose lipid compositions mimick that of the E . coli inner membrane . PR-39 induced a calcein release from large unilamellar vesicles, which is dependent upon the peptide concentration and upon the presence of negatively charged lipid (glycerophosphoglycerol) in the membrane . The binding study of PR-39 to dioleoylglycerophosphoglycerol vesicles suggests that nearly 100% of the added peptide is membrane-bound . Addition of PR-39 to a planar lipid bilayer induced a linear increase in the current but no channel formation was observed since no discrete steps of conductance occurred.

Tidsskr Nor Laegeforen, 1994 Sep 10, 114(21), 2495 - 7
{A Norwegian conference on updating of the treatment of Helicobacter pylori in peptic ulcer . Interessegruppe for Gastroenterologi}; Determination of trace impurities of peptides and alkaloids by capillary electrophoresis-ion spray mass spectrometry; Diagnostic Laboratory, Cornell University, Ithaca, NY 14850Two different mixtures have been analyzed by CE-UV-MS using selected ion monitoring (SIM) conditions to evaluate whether this technique can detect trace impurities in such mixtures . The first mixture consisted of two bioactive peptide analogues which included Lys-bradykinin (kallidin) and Met-Lys-bradykinin . The presence of 0.1% Lys-bradykinin was detected by SIM CE-MS but not by CE-UV at the 0.1% level as it migrated from the capillary column prior to the major component, Met-Lys-bradykinin . The second mixture consisted of two antibacterial alkaloids, berberine and palmatine . The presence of 0.15% palmatine was detected by CE-UV and SIM CE-MS at the 0.15% level as it migrated from the capillary column following the major component, berberine . These results suggest that SIM CE-MS offers the necessary separation efficiencies and sensitivity to provide a complementary analytical determination of trace components in such sample mixtures.

Biochemistry, 1994 Sep 6, 33(35), 10681 - 92
Mode of action of the antibacterial cecropin B2: a spectrofluorometric study; Gazit E et al.; Cecropin B2 (CecB) is a 35 amino acid residue, antibacterial peptide that was isolated from the hemolymph and cuticular matrix of the silkworm, Bombyx mori . Synthetic peptides with sequences corresponding to CecB and its truncated analogue, {3-->35}CecB, were synthesized and selectively labeled at their N-terminal amino acids with either 7-nitrobenz-2-oxa-1,3-diazol-4-yl (NBD) or rhodamine fluorescent probes . Utilization of these probes facilitated study of the interaction of cecropin with model phospholipid membranes at a high lipid/peptide molar ratio (approximately 3000:1), permitting investigation of the initial steps involved in this process . The surface partition coefficient of CecB, derived from binding isotherms of the NBD-labeled peptide, was 10-fold higher with acidic phospholipids than with zwitterionic ones, which correlates with the high efficiency of CecB and its analogues in permeating acidic phospholipid vesicles . Furthermore, a direct correlation was found between the antibacterial activity of CecB or its truncated analogues and the ability of their Rho-labeled analogues to interact with bacteria and human red blood cells . We propose that CecB binds phospholipid membranes preferentially as monomers lying on the surface, rather than cooperatively as bundles that form transmembranal pores via a "barrel stave" mechanism . This is based on the following: (i) the linearity of CecB's binding isotherms; (ii) the low energy transfer between membrane-embedded donor and acceptor-labeled CecB, even in the presence of a transmembrane potential; (iii) the surface localization of CecB's N-terminus; (iv) the need for more than 100 peptide molecules per phospholipid vesicle to induce initial ion leakage; and (v) the fact that CecB is a highly positively charged amphipathic alpha-helix, and therefore it is not expected to transverse the membrane as a monomer . We speculate that the non-cooperative binding of the peptides on the outer surface of the bacteria (i.e., no aggregation of CecB monomers) may help them to diffuse efficiently into the inner membrane, which is thought to be the target of antibacterial peptides.

South Med J, 1994 Sep, 87(9), 869 - 74
Neurotoxicity of antibacterial therapy; Thomas RJ; The increasing variety of drugs available for the treatment of bacterial infections has simultaneously increased the potential for toxicity . Neurologic toxicity of antibacterial therapy is generally underestimated in scope and severity; it may be classified as central, peripheral, or due to drug-interactions, several of which are potentially life-threatening . beta-Lactams and the quinolones are the drugs most commonly associated with seizures and encephalopathy . Drug-induced ototoxicity is common, and sensitive tests are now available for early diagnosis of both cochlear and vestibular toxicity . Testing in clinical practice is best restricted to subgroups at high risk . The aminoglycosides, tetracyclines, clindamycin, erythromycin, polymyxins, and possibly ampicillin have the potential to aggravate neuromuscular disease . Ethambutol, isoniazid, and chloramphenicol are toxic to the optic nerve; bismuth can cause a myoclonic encephalopathy . A number of less common and/or unusual toxicities are also discussed.

Am J Gastroenterol, 1994 Sep, 89(9), 1501 - 4
Triple therapy with sucralfate is not effective in eradicating Helicobacter pylori and does not reduce duodenal ulcer relapse rates; Pedrazzoli J Jr et al.; OBJECTIVES: The most used therapeutic schedule to eradicate Helicobacter pylori is the "triple therapy," which is based on the simultaneous use of a bismuth salt and two antibiotics . Sucralfate, a basic aluminum salt of sucrose sulfate, is supposed to have an antibacterial activity and is said to reduce the bacterial density of H . pylori . This randomized, prospective clinical trial compares the efficacy of an alternative oral triple therapy consisting of sucralfate, tinidazol, and tetracycline with a conventional therapy using ranitidine, with respect to H . pylori eradication and duodenal ulcer healing and recurrence in a 12-month follow-up . METHODS: Forty-three patients with active duodenal ulcers diagnosed at endoscopy were enrolled to receive either 1 g of sucralfate four times daily for 30 days, 500 mg of tetracycline four times daily, and 500 mg of tinidazol three times daily, for 10 days (group A; n = 23) or 150 mg of ranitidine twice daily for 30 days (group B; n = 20) . The groups were age- and sex-matched and balanced for tobacco use and H . pylori status . Compliance assessed by post-treatment interviews was considered high (all patients declared that they had ingested at least 80% of the drugs) . RESULTS: Both therapies were efficient in healing ulcers (group A, 95%; group B, 90%), the relapse rates were high in both groups (group A, 77%; group B, 89%), and the alternative triple therapy eradicated H . pylori in only 4% of the patients . CONCLUSION: Alternative oral triple therapy presented no significant advantage over ranitidine treatment of active ulcer disease.

Med Clin North Am, 1994 Sep, 78(5), 1049 - 65
Fungal pneumonia; Davies SF; Fungal pneumonias are rare but important . Sometimes the clinical presentation is identical to more common bacterial or atypical pneumonias . In such cases, the diagnosis is either not made or is made accidentally from diagnostic specimens obtained to determine the likely bacterial pathogen . Other cases look like routine bacterial or atypical pneumonia at presentation but do not improve or even progress as they are being treated with appropriate antibacterial agents . In such cases, it is important not to give a series of treatment courses with different antibacterial antibiotics that all cover essentially the same range of pathogens . Rather the diagnostic efforts must be escalated, progressing to more aggressive measures (fiberoptic bronchoscopy, fine needle aspiration, and rarely thoracoscopic or traditional open lung biopsy) until a specific diagnosis is reached . In some cases, there are clinical clues that point to a fungal cause . Attention to these clues can lead to early initiation of appropriate diagnostic sequences, faster diagnosis, and earlier initiation of specific therapy . A review of some of these clinical clues is provided in Table 1.

J Immunol, 1994 Sep 1, 153(5), 2302 - 12
Cytokine profile and ultrastructure of intraepithelial gamma delta T cells in chronically inflamed human gingiva suggest a cytotoxic effector function; Lundqvist C et al.; We have shown that gamma delta T cells in human gingiva have an intraepithelial location and, that in the chronic inflammatory disease periodontitis, the expression of CD45RO and CD8 or CD4 is induced on gamma delta T cells . To study the role of gamma delta T cells in local antibacterial responses, we determined the cytokine profiles of isolated human gingival cells . Different T cell subpopulations, isolated by positive selection with mAb-coated magnetic beads and macrophages, as well as epithelial cells, were analyzed for expression of mRNA for 15 cytokines by reverse transcriptase-PCR . The ultrastructure of gingival gamma delta T cells was also studied . The gamma delta T cells expressed mRNA for IFN-gamma, TNF-alpha, TGF-beta 1, and IL-6 . Expression of IFN-gamma was a consequence of inflammation . CD4+ gamma delta T cells expressed IFN-gamma only, whereas CD8+ gamma delta T cells expressed all four cytokines . CD8+ cells expressing IFN-gamma, TNF-alpha, and IL-6 in combination suggest a cytotoxic effector function . Gingival gamma delta T cells contained cytoplasmic electron-dense membrane-bound granules and multivesicular bodies that are ultrastructural characteristics of cytotoxic cells . Epithelial cells from inflamed gingiva expressed HLA-DR, CD1a, CD1c, and heat shock protein 60 on the cell surface . They also expressed mRNA for IL-1 beta, IL-6, IL-8, TNF-alpha, and TGF-beta 1 . Thus, epithelial cells may function as accessory cells in immune activation and, at the same time, be target cells for CD8+ gamma delta T cells reactive with CD1 Ag or heat shock protein . These results suggest that gamma delta T cells constitute a first line of defense in gingiva, preventing entrance of pathogens by cytotoxicity against infected and stressed epithelial cells, and by control of epithelial cell growth through secretion of regulatory cytokines.

Bone Marrow Transplant, 1994 Sep, 14(3), 459 - 61
Acanthamoeba meningoencephalitis after bone marrow transplantation; Anderlini P et al.; Two patients presented with fever and nodular pulmonary infiltrates 9 and 6 months after marrow transplantation for leukemia . The second patient also had painful subcutaneous nodules that subsequently ulcerated . Both had a history of sinusitis and both had recently been treated with corticosteroids . During treatment with antibacterial and antifungal antibiotics, they developed rapid mental deterioration, coma and/or seizures . CT findings included hydrocephalus with extensive cortical and periventricular hypodensities in the first patient, and hydrocephalus with a cerebellar hemorrhage and edema in the second patient . Cerebrospinal fluid had a low glucose and elevated protein levels with few erythrocytes and little or no pleocytosis . Despite therapy with broad-spectrum antibiotics, including coverage for opportunistic infections, both patients died . Autopsy revealed Acanthamoeba species causing necrotizing meningoencephalitis, pneumonitis and adrenalitis in the first patient and causing necrotizing meningoencephalitis and dermatitis in the second patient . While these are the only reported cases of disseminated Acanthamoeba infection in marrow transplant recipients, a review of the literature suggests that this organism may be a new cause of opportunistic infections.

J Nihon Univ Sch Dent, 1994 Sep, 36(3), 183 - 90
Comparison of the antibacterial effects on subgingival microflora of two different resorbable base materials containing doxycycline; Taner IL et al.; A study was conducted to evaluate the effects of local drug delivery on subgingival plaque flora using hydroxypropylmethylcellulose (HPMC) and methylcellulose (MC) base material containing 40% doxycycline (DOXY) . Eleven patients who had at least four pockets exceeding 5 mm in depth associated with a single rooted tooth were selected from volunteers after an initial examination . Two of the pockets were chosen at random for insertion of the HPMC and MC strips twice a week for 6 w . One pocket received no treatment, and the other was debrided and root-planed only . Baseline and follow-up measurements at 0, 1, 3, 6, and 10w included probing depth, gingival shrinkage, bleeding on probing and crevicular fluid flow . Subgingival bacterial samples were also taken for dark-field microscopy . In vitro drug release from the HPMC strips was greater than that from MC . Significant improvements in many clinical parameters occurred in the pockets treated with HPMC or MC strips, or mechanical debridement . There was a marked decrease in the relative proportions of motile organisms during and after treatment.

Br Vet J, 1994 Sep-Oct, 150(5), 439 - 49
The use of arthroscopy in the treatment of septic arthritis in two Highland calves; Munroe GA et al.; Septic polyarthritis is a common condition in the young bovine animal . Systemic antibacterial treatment is often not sufficient to eliminate the infection, particularly in the subacute or chronic stages . More invasive procedures, including joint drainage and arthrotomy, are often unsatisfactory, either because of the failure to cure the condition or because of the associated complications . This article describes the use of arthroscopy in the treatment of infectious arthritis and osteomyelitis in two calves . In one case, two joints were explored and debrided successfully during the same intervention . The advantages of this technique to treat septic arthritis in the bovine are described and discussed . The use of diagnostic ultrasonography to confirm joint involvement is also described.

J Antibiot (Tokyo), 1994 Sep, 47(9), 1052 - 64
Synthesis and in vitro antibacterial activities of 3-thiazol-4-yl-1-carba-1-dethiacephalosporins; Hornback WJ et al.; The synthesis and microbiological evaluation of a new series of 3-thiazol-4-yl-carba-1-dethiacephalosporins is described . Structure activity relationship was achieved by changing substitution at the 2-position of the thiazole moiety . The result was a marked variance of microbiological activity in the C7 side-chain derivatives . ATMO derivatives possess potent activity against both Gram-positive and Gram-negative bacteria . For example, MICs (microgram/ml) of LY215226 against representative organisms are as follows: S . aureus 0.25, S . pneumoniae 0.008, H . influenzae 0.008, E . coli 0.25, K . pneumoniae 0.008, E . cloacae 0.5, S . typhi 0.25, and M . morganii 0.25.

Curr Genet, 1994 Sep, 26(3), 281 - 4
Energy-dependent mitochondrial mutagenicity of antibacterial ofloxacin and its recombinogenic activity in yeast; Obernauerova M et al.; Ofloxacin, a specific inhibitor of bacterial topoisomerase II, is known to inhibit the growth of yeast cells and to induce rho- mutants in the yeast S . cerevisiae . The frequency of ofloxacin-induced petite mutants under non-growth conditions was found to be strongly diminished when the cells were depleted in intramitochondrial ATP . Under optimal conditions of mitochondrial mutagenesis the drug induced mitotic recombination and reverse mutation in diploid strains but failed to cure either killer plasmids or the 2 microns DNA of dividing cells . The sensitivity to ofloxacin of the strains deficient in the DNA strand-break repair pathway (rad52) was significantly higher then that of the wild-type strains and of the mutants deficient in excision or mutagenic DNA repair . The results are compatible with the idea that the cytotoxic and genetic activity of ofloxacin in yeast probably results from the inhibited DNA ligation function of topoisomerase II creating DNA breaks that are reparable through the recombination repair pathway.

Boll Chim Farm, 1994 Sep, 133(8), 527 - 31
Studies on arylfuran derivatives . Part III . Synthesis and antibacterial properties of arylfurfurylidene-isatin-beta-hydrazones and their Mannich bases; Shivarama Holla B et al.; A number of N1 - arylfurfurylidene isatin -beta- hydrazones were prepared as possible antibacterial agents . They were subjected to Mannich reaction in the presence of secondary amines . The hydrazones and their Mannich bases were screened for their antibacterial properties against both Gram-negative bacteria.

Antimicrob Agents Chemother, 1994 Sep, 38(9), 1984 - 90
Stimulation of genetic instability and associated large genomic rearrangements in Streptomyces ambofaciens by three fluoroquinolones; Volff JN et al.; In Streptomyces ambofaciens NSA2002, pigmented wild-type colonies spontaneously give rise to pigment-negative (Pig-) mutants at a frequency of about 0.5% . This genetic instability is related to large deletions which can be associated with amplifications of DNA sequences . The influence of three fluoroquinolones (ciprofloxacin, enoxacin, and norfloxacin) on this property was investigated . At a survival rate higher than 60%, most colonies showed a patchwork phenotype consisting of phenotypically heterogeneous colonies harboring numerous mutant sectors . Moreover, the frequency of Pig- mutants rose to more than 90% at survival rates equal to or higher than 10% . Induced Pig- mutants showed the same phenotypical features as did spontaneous mutants . Most of them also harbored deletions, associated in some cases with DNA amplifications, in two loci of the large unstable region, AUD6 and AUD90 (derived from amplifiable unit of DNA) . The size of deletions in induced mutants could rise to 1.5 Mb . These results show that ciprofloxacin, enoxacin, and norfloxacin greatly stimulate genetic instability and the occurrence of DNA rearrangements in S . ambofaciens . Moreover, these three fluoroquinolones had the same rank order for both toxic (i.e., antibacterial) and genotoxic activities . If the antibacterial effect of fluoroquinolones in S . ambofaciens is due to their interference with DNA gyrase, as shown for some other organisms, the genotoxic effect observed could be due to their interaction with this type II topoisomerase . This suggests that DNA gyrase is involved in the process of genetic instability in S . ambofaciens.

Rozhl Chir, 1994 Sep, 73(6), 298 - 9
{Prophylaxis with ciprofloxacin in transurethral surgery}; Sobek M et al.; The purpose of the study was to compare in a prospective randomized study the effect of three doses of prophylactic administration of ciprofloxacin in 25 patients and a control group of 26 patients without prophylactic antibiotic treatment in conjunction with transurethral surgery . In the group of patients with prophylaxis there is a significantly lower incidence of clinical manifestations of infection, as compared with the group of patients without prophylaxis which reduces the necessity to administer antibacterial drugs during the postoperative period.

Urology, 1994 Sep, 44(3), 422 - 4
Improved technique of laparoscopic nephrectomy for multicystic dysplastic kidney; Emmert GK Jr et al.; We report removal of a multicystic dysplastic kidney with a laparoscopic technique that uses only three trocar sites . Additionally, we have found placement of a ureteral catheter and full mechanical and antibacterial bowel cleansing unnecessary . The role of this surgery in the management of multicystic dysplastic kidney is discussed.

Afr J Med Med Sci, 1994 Sep, 23(3), 257 - 60
The antibacterial effect of honey on diarrhoea causing bacterial agents isolated in Lagos, Nigeria; Obi CL et al.; The antibacterial effect of local honey on local isolates of bacterial agents of diarrhoea was determined by an in vitro method involving the impregnation of filter paper discs in undiluted honey and different honey concentrations ranging from 10%-50% . The discs were later placed on plates that have been seeded with the different bacteria and zones of inhibition of growth were measured after a 48 hr . period of incubation . Results presented show that undiluted honey and honey at concentrations of 40% and above were inhibitory to all enteropathogens tested . Zones of inhibition of growth around the disc margin of the various enteropathogens tested ranged from 16-18mm in diameter for the local undiluted honey and 7-12mm in diameter for concentrations of honey at 40% and 50% . The possible mechanisms of this inhibitory effect of local honey are discussed.

J Pharm Sci, 1994 Sep, 83(9), 1357 - 62
Quantitative structure-hydrophobicity and structure-activity relationships of antibacterial gramicidin S analogs; Katayama T et al.; The structure-hydrophobicity-antibacterial activity relationships of gramicidin S and its analogs retaining a beta-pleated sheet structure were examined quantitatively with physicochemical substituent and molecular parameters using regression analyses . Variations in their apparent hydrophobicity in an octanol/buffer (pH 7) system, log P' (O/W), were analyzed in terms of the "effective" hydrophobicity and steric parameters of side chain substituents of residues at certain positions in the molecule; however, some of the conformational factors have not been fully defined . For the partitioning into liposomes and the growth inhibitory activity against species of Gram-positive bacteria, the log P' (O/W) value simulated the hydrophobic effects of gramicidin S and its analogs better than substituent parameters . The side chain hydrophobicity was assumed to work together with effects attributed to variations in the entire cyclic peptide structure including conformational components undefined in the structure-log P' (O/W) analysis in these activities.

Drugs, 1994 Sep, 48(3), 404 - 30
Lansoprazole . A reappraisal of its pharmacodynamic and pharmacokinetic properties, and its therapeutic efficacy in acid-related disorders; Spencer CM et al.; Lansoprazole is a benzimidazole derivative that effectively decreases gastric acid secretion, regardless of the primary stimulus, via inhibition of gastric H+,K(+)-adenosine triphosphatase (ATPase) . It provides effective symptom relief and healing of peptic ulcer and reflux oesophagitis after 4 to 8 weeks of therapy and appears to prevent recurrence of lesions when administered as maintenance therapy . When administered at therapeutic dosages, lansoprazole produced higher healing rates than ranitidine or famotidine in patients with duodenal and gastric ulcers . Lansoprazole heals duodenal ulcers more rapidly than ranitidine or famotidine . Relief of ulcer symptoms in lansoprazole recipients is at least equivalent to, and tends to be more rapid than, that in patients receiving histamine H2-receptor antagonists . In comparisons with omeprazole 20 mg/day, lansoprazole 30 mg/day produced duodenal ulcer healing more rapidly and reduced ulcer pain to a greater extent at 2 weeks, but overall healing rates were similar after 4 weeks of therapy . At therapeutic dosages, lansoprazole produces superior healing and symptom relief of reflux oesophagitis in comparison with ranitidine, and it tends to relieve heartburn more effectively than omeprazole, although both agents produce equivalent healing . Healing of peptic ulcers or reflux oesophagitis refractory to histamine H2-receptor antagonists occurs after 8 weeks in the majority of patients treated with lansoprazole, and lansoprazole and omeprazole demonstrate similar efficacy in patients with refractory peptic ulcers . In patients with Zollinger-Ellison syndrome, lansoprazole effectively controls mean basal gastric acid output . Lansoprazole is generally well tolerated in clinical trials . The incidence of adverse effects is similar to that of omeprazole, ranitidine and famotidine in comparative studies . Combination therapy with lansoprazole and antibacterial agents such as amoxicillin, tinidazole, roxithromycin and/or metronidazole appears to eradicate Helicobacter pylori in 22 to 80% of patients with this organism . Limited data also suggest that lansoprazole may have superior activity against H . pylori in comparison with omeprazole, although the clinical relevance of this preliminary finding requires further confirmation . Thus, lansoprazole may be considered as alternative to existing antisecretory agents available for the treatment of acid-related disorders, particularly because it may provide more rapid healing and relief of symptoms.

J Chromatogr A, 1994 Aug 19, 677(2), 377 - 84
Quantitative analysis of quaternary ammonium antiseptics using thin-layer densitometry; Paesen J et al.; A thin-layer chromatography method for quantitative analysis of quaternary ammonium antiseptics is described . Silanized silica gel was used as the stationary phase . The mobile phase consisted of methanol-25% (m/v) sodium acetate solution-acetone (65:35:20) . The method is able to separate the chain homologues of benzalkonium chloride, cetylpyridinium chloride and cetrimide . Detection was performed using a colour reaction with potassium triiodide solution . The different homologues were quantified using UV densitometry at 400 nm . A number of commercial samples was analysed using this method . From the results it appears that it is worthwhile to have a limit test for the composition of quaternary ammonium antiseptics in pharmacopoeial monographs, the more so as the antibacterial activity depends on it.

Eur J Biochem, 1994 Aug 15, 224(1), 257 - 63
Permeabilization of the mitochondrial inner membrane by short cecropin-A-melittin hybrid peptides; Diaz-Achirica P et al.; A number of cecropin-A-melittin hybrid peptides have previously been shown to be potent antibacterial agents {Andreu, D., Ubach, J., Boman, A., Wahlin, B., Wade, D., Merrifield, R . B . & Boman, H . G . (1992) FEBS Lett . 296, 190-194} . In the present report we analyze their action on biological systems using rat liver mitochondria as a test system . We demonstrate that the longest peptide, cecropin-A-(1-8)-melittin(1-18) permeabilizes the mitochondrial inner membrane allowing the movement of both charged and non-charged solutes . Concentrations used have already been shown to be bactericidal . This effect is also demonstrated under respiring conditions where succinate oxidation is uncoupled . Shorter analogs also permeabilize mitochondria although at ten-fold higher concentrations . Heparin potentiates the peptide effects at low concentrations, while at high concentration it becomes inhibitory . We propose that the cecropin-melittin analogs disrupt the mitochondrial membrane in a detergent-like mode rather than by creating selective channels as had been previously suggested.

FEBS Lett, 1994 Aug 8, 349(3), 338 - 42
Immunochemical identification and translocation of protein kinase C zeta in human neutrophils; Dang PM et al.; Western blots of human polymorphonuclear leukocyte (PMN) extracts were immunostained with antibodies specific for various protein kinase C (PKC) isoforms . Two bands corresponding to PKC type zeta with apparent molecular masses of 81 kDa and 76 kDa were identified in the cytosolic fraction of resting cells, in addition to PKC types alpha and beta . PKC zeta was apparently abundant, like PKC beta, whereas PKC delta, -epsilon, and -gamma were not detectable . Following short stimulation (5 min) of PMN with phorbol-12-myristate-13-acetate (1 microgram/ml), physical translocation of PKC zeta from the cytosol to the plasma membrane fraction occurred, although this isoform does not bind phorbol esters . These data show that, in addition to the two calcium-dependent isoenzymes alpha and beta, human PMN express a calcium-independent isoenzyme zeta which translocates in stimulated cells, suggesting a role in the regulation of antibacterial activities.

Adv Ther, 1994 Sep-Oct, 11(5), 269 - 75
Ready-to-use pefloxacin infusion for surgical prophylaxis; Bapat RD et al.; The efficacy of pefloxacin in preventing postsurgical infection was demonstrated in an open, comparative, randomized clinical trial . The 120 evaluable patients were divided into four groups of 30 each . Group A served as controls . Groups B, C, and D received one, two, and six doses, respectively, of pefloxacin 400 mg in 100-mL solution as an intravenous infusion . The majority of treated patients benefited from pefloxacin therapy, with only 3% to 7% developing infection . In contrast, 20% of the placebo group developed infection within 5 days after surgery . Two of the 90 treated patients experienced mild side effects . One to six doses of ready-to-use pefloxacin infusion may be administered safely to provide antibacterial coverage during surgery.

Sci Total Environ, 1994 Aug 2, 152(2), 143 - 52
Effects of antibacterial agents on transformation of fatty acids in sediment from a marine fish farm site; Johnsen RI; The conversion of fatty acids in marine fish farm sediment from a simulated abandoned site was investigated . Five containers of aquaculture sediment were followed in 1 year . Antibacterial agents: oxytetracycline, flumequine and oxolinic acid, respectively, were added to three of the containers, while two were controls . The fatty acid composition in the sediment was examined by direct methanolysis on sediment, high-resolution gas chromatography and multivariate data-analysis . The total amount of fatty acids decreased strongly in all containers and the fatty acid profile in the sediment changed clearly towards the profile of natural, unaffected sediment with time . During the experimental period, the added drugs had a retarding effect on the transformation of fatty acids in the sediment . This effect, however, was not detectable after 10 months.

J Dermatol Surg Oncol, 1994 Aug, 20(8), 538 - 40
Utility of topical benzoyl peroxide for prevention of surgical skin wound infection; Bencini PL et al.; BACKGROUND . Benzoyl peroxide is a powerful oxiding agent with broad spectrum germicidal activity and good liposolubility . Therefore, it may represent a good agent for prevention of wound infection in areas with high density of sebaceous glands . OBJECTIVE . The aim of this study was to analyze the effectiveness of topical benzoyl peroxidase gel for prevention of surgical skin wound infections in the centrofacial area . METHODS . A prospective study was performed on 673 patients . The patients were divided into two groups . Group A, 335 patients, was given no antibacterial prophylaxis . In group B, 338 patients, prophylactic medication with a gel containing 10% benzoyl peroxide was performed once a day for the 7 days before the surgery . RESULTS . Thirteen of 673 patients had wound infections (1.93%) . Eleven of these 13 patients were in group A (3.24%) and two were in group B (0.59%) (P < .01) . CONCLUSIONS . Topical benzoyl peroxide is an efficacious, harmless, and inexpensive agent for prevention of wound infections in seborrheic regions.

Eur J Biochem, 1994 Aug 1, 223(3), 1027 - 33
Antibacterial peptides and mitochondrial presequences affect mitochondrial coupling, respiration and protein import; Hugosson M et al.; Cecropins A and P1, antibacterial peptides from insects and from pig and some related peptides released respiratory control, inhibited protein import and at higher concentrations also inhibited respiration . However, PR-39, an antibacterial peptide from pig intestine, was found to be almost inert towards mitochondria . The concentrations at which the three mitochondrial functions were effected varied for different peptides . Melittin, magainin and Cecropin-A-(1,13)-Melittin(1,13)-NH2, a hybrid between cecropin A and melittin, were most potent, while the two cecropins acted at higher concentrations . The biosynthesis of cecropin A is known and the intermediates are synthesized . We have used four peptides from this pathway to investigate their effects on coupling, respiration and protein import into mitochondria . Mature cecropin A followed by the preproprotein were most aggressive whereas the intermediates were less active or inert . The efficiency of different derivatives of cecropin A as uncouplers correlates well with their capacity to release membrane potential measured as fluorescence quenching of Rhodamine 123 . Inhibition of respiration was found to be dependent on membrane potential and was most pronounced with mature cecropin A, less so with its three precursors . We also found that three peptides derived from mitochondrial presequences showed antibacterial activity . It is concluded that, there are similarities in the functions of antibacterial peptides and mitochondrial presequences, uncoupling activity in mitochondria cannot be correlated with the antibacterial activity (contrary to a previous suggestion), the processing of preprocecropin A may have evolved in such a way that there is a minimum of membrane damage from the intermediates in the pathway, and peptides produced for delivery outside of an animal have evolved to be more aggressive against mitochondria than peptides for delivery inside of the animal.

Scand J Immunol, 1994 Aug, 40(2), 187 - 94
Bacteriostatic activity of BCG/PPD-activated macrophages against Mycobacterium fortuitum does not involve reactive nitrogen or oxygen intermediates; Nibbering PH et al.; Mycobacteria preferentially reside in resident macrophages whereas activated macrophages are presumed to eliminate the bacteria effectively . The aim of the present study was to determine the antibacterial activities of resident and activated murine peritoneal macrophages against Mycobacterium fortuitum and the intracellular mechanisms involved . After phagocytosis M . fortuitum could not be killed by either BCG/PPD-activated and IFN-gamma-activated macrophages and resident macrophages . The mycobacteria did not multiply in BCG/PPD-activated macrophages and the rate of proliferation of M . fortuitum in IFN-gamma-activated macrophages was only slightly inhibited compared to that in resident macrophages . Experiments with selective inhibitors of the production of reactive nitrogen intermediates (RNI) and reactive oxygen intermediates (ROI) demonstrated that these factors are not essential for the mycobacteriostatic activity of BCG/PPD-activated macrophages . After phagocytosis of M . fortuitum, BCG/PPD-activated and IFN-gamma-activated macrophages produced substantial amounts of both RNI and ROI . No correlation was found between the levels of these intermediates and the proliferation of M . fortuitum in the macrophages . In conclusion, BCG/PPD-activated macrophages are bacteriostatic, but not bacteriocidal for M . fortuitum and the former does not involve reactive nitrogen and oxygen intermediates.

J Clin Invest, 1994 Aug, 94(2), 672 - 82
Individual and synergistic effects of rabbit granulocyte proteins on Escherichia coli; Levy O et al.; Affinity purification of crude acid extracts of rabbit polymorphonuclear leukocytes using Escherichia coli (J5) as adsorbent yields the bactericidal/permeability-increasing protein (BPI), two 15-kD species (p15s), and the two most potent (cationic) defensin species (neutrophil peptides {NP} -1 and -2) . Tested in buffered isotonic medium, the relative antibacterial potency of these proteins against E . coli J5 is BPI (IC50 0.2 nM) > p15A (10 nM) > NP -1 (400 nM) . Sublethal doses of p15A or NP-1 can synergize with BPI to decrease the dose required to inhibit the growth of E . coli by up to 50-fold . BPI and p15A display similar features of antibacterial action distinct from defensin NP-1, but NP-1 acts synergistically only with BPI and not with p15A . All aspects of the combined action of BPI and NP-1 resemble those observed with higher concentrations of BPI alone, implying that NP-1 enhances BPI potency . Neither NP-1 nor p15A alter the amount of BPI binding to E . coli but BPI enhances binding of p15A to E . coli, raising the possibility that synergy between these two proteins may occur at least partially at the level of binding . The potent synergistic actions of these proteins can also be demonstrated against serum-resistant clinical isolates of encapsulated E . coli tested in whole blood and plasma ex vivo, suggesting that such combined action may contribute to host defense in vivo.

J Ethnopharmacol, 1994 Aug, 44(1), 35 - 40
Antibacterial activity of plant extracts used externally in traditional medicine; Brantner A et al.; Plants of 28 families, selected on the basis of medicinal folklore reports and literature data, were studied in a screening program . Aqueous extracts of plants used externally for the treatment of infected skin lesions were tested for their antibacterial potential . The results indicated that about 60% of the plant extracts tested exhibited some level of antibacterial action.

J Vet Pharmacol Ther, 1994 Aug, 17(4), 309 - 16
The sulfonamide-diaminopyrimidine story; van Miert AS; This paper is devoted to chemotherapy in the sense that Paul Ehrlich (Nobel Prize winner in 1908) coined the word: to describe the cure of infectious diseases by chemical agents without injury to the organism infected . This approach, essentially that of selective toxicity, is applicable to the investigations performed by Gerhard Domagk (Nobel Prize winner in 1939), which resulted in the development of Prontosil rubrum . This agent was active in vivo but not in vitro . Trefouel supposed that the in vivo action was due to a metabolite of the drug (sulfanilamide), a hypothesis later proved by Fuller in 1937 . Sulfanilamide was a simple agent, easy to manufacture and free of patent rights . Thus, more than 5400 derivatives were synthesized and studied in the decades that followed . Research on the side-effects of sulfonamides resulted in the development of diuretics and antidiabetogenic agents . The resurgence of interest in sulfonamides in following years has been associated with the development of diaminopyrimidines by Hitchings (Nobel Prize winner in 1988) . It soon became evident that combinations of these drugs produced potent synergistic effects . Trimethoprim, a potent antibacterial agent of this series, was selected for combining with sulfonamides such as sulfadiazine . This line is still continued and even recently new diaminopyrimidine derivatives such as aditoprim and baquiloprim have been synthesized having superior properties in farm animal species . Thus, even nowadays the principles of Ehrlich continue to have a major impact on the development of new veterinary drugs.

Planta Med, 1994 Aug, 60(4), 360 - 4
Caffeoylquinic acids and some biological activities of Pluchea symphytifolia; Scholz E et al.; From the aerial parts of Pluchea symphytifolia, four known and two new caffeoylquinic acids, 1,3,4,5-tetra-O-caffeoylquinic acid and 1,3-di-O-{3,4,-bis-(3,4-dihydroxyphenyl)-cyclobutane-1,2-dicarbonyl}- 4,5-di-O-caffeoylquinic acid, and two flavonols were isolated and their structures elucidated by mass and NMR spectroscopy and by chemical degradation . The aqueous extract had weak antibacterial and weak antisecretory effects; the lipophilic extract showed a modest anthelmintic activity . The higher caffeoylated quinic acids participated in the antibacterial and anthelmintic effect of the extracts.

Oral Surg Oral Med Oral Pathol, 1994 Aug, 78(2), 232 - 8
Radiographic and microbiologic evaluation of posttreatment apical and periapical repair of root canals of dogs' teeth with experimentally induced chronic lesion; Leonardo MR et al.; The objective of the present study was to evaluate radiographically and bacteriologically apical and periapical repair in dogs' teeth with induced chronic periapical lesions with the use of two different operative techniques (techniques 1 and 2) . The study was conducted on 40 root canals of upper and lower premolars from two dogs aged approximately 12 months . Periapical lesions were induced by leaving the root canals exposed to the oral environment for 5 days and then sealing them with zinc oxide-eugenol for 45 days . After this period, radiographic examination revealed the occurrence of a radiolucent lesion and endodontic treatment was started . The two techniques did not differ in terms of chemomechanical preparation, final filling, or type of cement, but differed in terms of irrigating solution and the presence of an antibacterial dressing . Thus 4% to 6% hypochlorite and hydrogen peroxide (10 volumes) were used in technique 1 during chemomechanical preparation and an antibacterial dressing based on calcium hydroxide was applied between sessions, whereas Dakin's fluid (0.5% sodium hypochlorite solution) and a final filling with no antibacterial dressing were used in technique 2 . After chemomechanical preparation, the root canals were filled with gutta-percha cones and Sealapex (Sealapex-Sybron, Kerr, Sao Paulo, Brazil), and the animals were killed 270 days after the final filling . Blocks were cut into 6-microns sections and stained by the Brown and Brenn method.(ABSTRACT TRUNCATED AT 250 WORDS)

Br J Dermatol, 1994 Aug, 131(2), 177 - 83
Expression of classical and non-classical MHC class I antigens in murine hair follicles; Paus R et al.; Not all keratinocytes in human and rat hair follicles express MHC class I antigens (MHC I) . In the present study, we report the first immunohistological profile of classical and non-classical MHC I expression in the skin of adolescent C57 BL-6 mice during the induced hair cycle . MHC I immunoreactivity (H-2b, H-2Db) is absent in the matrix and inner root sheath of growing (= anagen) hair follicles, and the dermal papillae are H-2b negative during catagen and telogen . This lack of normal MHC I expression may serve to sequester potentially damaging autoantigens from immune recognition . In addition, we present the first evidence of non-classical MHC class I antigen expression in normal mammalian skin: during the entire hair cycle, the distal hair follicle shows strong Qa-2 immunoreactivity, which appears to be restricted to an epithelial follicle compartment densely populated by gamma-delta T cells with which Qa-2 molecules may interact as part of a primitive antibacterial defense system of the follicle . The murine hair cycle is an attractive model for dissecting the functional roles of H-2b and Qa-2 molecules in hair biology and in related tissue-interaction systems.

Am J Trop Med Hyg, 1994 Aug, 51(2), 180 - 2
Brain abscess due to infection with Entamoeba histolytica; Ohnishi K et al.; We successfully treated a serious case of Entamoeba histolytica infection showing brain abscess, meningitis, and liver abscess by oral administration of metronidazole, intramuscular injection of dehydroemetine, and drainage of the brain abscess . The diagnosis of amebic brain abscess was based on a combination of clinical symptoms and signs, computed tomography and magnetic resonance imaging findings, a positive serologic test result for E . histolytica, a dramatic response to anti-amebic drugs after an ineffective therapeutic history with antibacterial drugs, and application of the polymerase chain reaction method.

J Chemother, 1994 Aug, 6 Suppl 3, 16 - 8
{Immune response to antibiotics in patients with secondary immunodeficiencies}; Meroni PL; A biological response modifier (BRM) has been defined as an agent able to modulate effector mechanisms or mediators of host defence . Some antibiotic molecules have been shown to display a BRM like activity, being able to enhance immune responses (certain cephalosporins), to synergize with the immune effectors (macrolides, quinolones) or alternatively, to depress immune functions (tetracyclines or antimycotic drugs) . The BRM-like activity of different antibiotic molecules has been widely reported in in vitro studies as well as ex vivo in experimental animal models . Only recently some Authors have approached the problem by investigating whether the in vivo administration of antibiotic was able to affect different immune effector functions, either in healthy subjects or in patients . The main question in the field is the possible clinical impact of the connections between antibiotics and the immune system, particularly in subjects with acquired immunodeficiency in whom the impairment of the immune responses leads to increased susceptibility to infectious processes . Ex vivo data seem to suggest that cefodizime, one of the newest third-generation cephalosporins, is able to enhance phagocyte and mononuclear cell functions in healthy volunteers, thus confirming the possibility of combining an antibacterial efficacy with the ability to restore or enhance immune responses . Comparable data in studies investigating the effect of cefodizime on immune functions in immunocompromised patients such as elderly subjects, hemodialyzed or diabetic patients, BPCO subjects, patients undergoing surgical stress and patients with multiple myeloma are more important from a practical clinical point of view.(ABSTRACT TRUNCATED AT 250 WORDS)

Zh Mikrobiol Epidemiol Immunobiol, 1994 Aug-Sep, Suppl 1, 80 - 3
{The differential microbiological diagnosis of bacteremia and sepsis and the results of its practical use}; Kotliarova GA et al.; A rapid method for the detection of classical forms of bacteria and their cell-wall defective (CWD) variants in the blood has been developed and approved . The method is based on the kinetic analysis of bacterial growth with the use of nephelometry . The analysis lasts 3-10 hours . The method permits the differential microbiological diagnosis of bacteremia and sepsis, as well as the rapid control of the effectiveness of antibacterial therapy . The rapid method has revealed that in the presence of antibacterial therapy infective agents persist in the blood as CWD variants and not in the classical bacterial form, which sharply decreases the reliability of the traditional diagnostic method . CWD variants have been detected in the blood of patients treated with the preparations of cephalosporin, chinolon, aminoglycoside, dioxydin, etc.

Biol Pharm Bull, 1994 Aug, 17(8), 1144 - 6
Biopolymers from marine invertebrates . XIV . Antifungal property of Dolabellanin A, a putative self-defense molecule of the sea hare, Dolabella auricularia; Iijima R et al.; Dolabellanin A (DAA), the antineoplastic and antibacterial glycoprotein purified from the albumen gland of Dolabella auricularia, showed an antifungal activity . DAA suppressed fungal growth completely at a concentration of over 2 micrograms/ml, and the colony forming ability of the fungus was significantly decreased after contact with DAA . These results indicate that DAA is an antifungal protein and its mode of antifungal activity is fungicidal.

Fogorv Sz, 1994 Aug, 87(8), 237 - 43
{Effect of various mouthwashes on wound healing after tooth extraction}; Denes J et al.; The results of the clinical tests involving 200 patients show that after extraction the use of Meridol, NaF and Chlorhexidine mouthrinses along with careful mouth hygiene helps healing to a great extent . The antiseptic affect of solutions in case of solutions of fluoride content are manifested in an antibacterial way, while solutions of chlorhexidine content act in an antiseptic way . Furthermore the solutions foster good oral hygiene and in this way lessen the number of complications . This is shown by the decreased frequency rate of gingivitis and also the opinions of the patients . Their reports confirm that there is less foetor ox ore, pain and functional insufficiency in mastication . Based on these facts we can state that any of the three mouthrinses considerably helps complication-free healing.

Antibiot Khimioter, 1994 Aug, 39(8), 44 - 7
{Ligenten--a combination drug with anesthetic and antibacterial action for local use in urology and gynecology}; Darenkov AF et al.; Ligenten gel is a combined dosage form containing gentamicin (a broad spectrum antibiotic), lidocaine (an anesthetic) and ethonium (an antiseptic) . The hydrogel sodium carboxymethylcellulose in combination with polyvinylpyrrolidone is used as the ligenten base . The clinical trials in urologic and gynecologic patients showed that ligenten had a high therapeutic efficacy in the treatment of inflammatory diseases, as well as an anesthetic action in instrumental examinations and surgical endoscopic manipulations.

Baillieres Clin Rheumatol, 1994 Aug, 8(3), 553 - 73
Serum amyloid A: an acute phase apolipoprotein and precursor of AA amyloid; Marhaug G et al.; Serum amyloid A is an acute phase protein complexed to HDL as an apoprotein . The molecular weight is 11.4-12.5 kDa in different species and the protein has from 104 to 112 amino acids, without or with an insertion of eight amino acids at position 72 . The protein is very well conserved throughout evolution, indicating an important biological function . The N-terminal part of the molecule is hydrophobic and probably responsible for the lipid binding properties . The most conserved part is from position 38 to 52 and this part is therefore believed to be responsible for the until now unknown biological function . The protein is coded on chromosome 11p in man, and chromosome 7 in mice, and found in all mammals until now investigated, and also in the Peking duck . In the rat a truncated SAA mRNA has been demonstrated, but no equivalent serum protein has been reported . Acute phase SAA is first of all produced in hepatocytes after induction by cytokines, but extrahepatic expression of both acute phase and constitutive SAA proteins have been demonstrated . Several cytokines, first of all IL-1, IL-6 and TNF are involved in the induction of SAA synthesis, but the mutual importance of these cytokines seems to be cell-type specific and to vary in various experimental settings . The role of corticosteroids in SAA induction is somewhat confusing . In most in vitro studies corticosteroids show an enhancing or synergistic effect with cytokines on SAA production in cultured cell . However, in clinical studies and in vivo studies in animals an inhibitory effect of corticosteroids is evident, probably due to the all over anti-inflammatory effect of the drug . Until now no drug has been found that selectively inhibits SAA production by hepatocytes . Effective anti-inflammatory or antibacterial treatment is the only tool for reducing SAA concentration in serum and reducing the risk of developing secondary amyloidosis . The function of SAA is still unclear . Interesting theories, based on current knowledge of the lipid binding properties of the protein and the relation to macrophages, in the transportation of cholesterol from damaged tissues has been advanced . A putative role in cholesterol metabolism is supported by the findings of SAA as an inhibitor of LCAT . The potential that SAA is a modifying protein in inflammation influencing the function of neutrophils and platelets is interesting and more directly related to the inflammatory process itself.(ABSTRACT TRUNCATED AT 400 WORDS)

FEMS Microbiol Lett, 1994 Aug 1, 121(1), 81 - 5
Inactivation of bleomycin by an N-acetyltransferase in the bleomycin-producing strain Streptomyces verticillus; Sugiyama M et al.; Bleomycin-producing Streptomyces verticillus ATCC15003 possesses a bleomycin acetyltransferase which inactivates the drug in the presence of acetyl coenzyme A . The site of acylation in enzymically prepared acetylbleomycin A2 was determined by nuclear magnetic resonance analysis; the primary amino group of the beta-aminoalanine moiety of bleomycin was acetylated Acetylbleomycin A2 had no detectable antibacterial activity and did not induce in vitro DNA degradation.

J Ethnopharmacol, 1994 Jul 8, 43(2), 125 - 33
Testing garlic for possible anti-ageing effects on long-term growth characteristics, morphology and macromolecular synthesis of human fibroblasts in culture; Svendsen L et al.; The beneficial effects claimed for the use of garlic as a nutritional supplement include detoxification, antioxidation, antifungal activity, antibacterial activity, tumour suppression and, possibly, anti-ageing and rejuvenating effects . We have used the Hayflick system of cellular ageing in culture in order to test garlic for its anti-ageing effects on long-term growth characteristics, morphology and macromolecular synthesis of human skin fibroblasts . Our results show that an addition of garlic extract into the normal cell culture medium can support serial subculturing for over more than 55 population doublings in 475 days, and that this treatment has some youth-preserving, anti-ageing and beneficial effects on human fibroblasts in terms of maximum proliferative capacity and morphological characteristics . In comparison, similar or lesser doses of garlic extracts are growth inhibitory for cancerous cells that could not be grown over longer periods in the presence of garlic . To our knowledge, this is the first report of the effects of garlic on the long-term growth characteristics and macromolecular synthesis of normal human skin cells, the results of which have applications for both anti-ageing and anti-cancer research.

J Immunol, 1994 Jul 1, 153(1), 343 - 52
Superinduction of cytokine gene transcription by ciprofloxacin; Riesbeck K et al.; In addition to their antibacterial properties, certain antibiotics are also biologic response modifiers . The fluorinated 4-quinolone, ciprofloxacin, for example, up-regulates IL-2 and IFN-gamma production in PBLs stimulated in vitro . In the present study, ciprofloxacin was shown to increase the levels of mRNA for IL-1 alpha, IL-2 and its receptor, IFN-gamma, IL-3, IL-4, granulocyte-macrophage/CSF, TNF-alpha, and lymphotoxin . As investigated with different T cell mitogens and alloantigens, the up-regulation of IL-2 production by ciprofloxacin was found to be independent of the mode of stimulation . Analysis of transcription activity showed that ciprofloxacin enhances IL-2 gene induction . The concentrations of nuclear factor of activated T cells (NF-AT-1) and AP-1 were also found to be increased by ciprofloxacin . Thus, ciprofloxacin interferes with a regulative pathway common to several cytokines.

J Clin Periodontol, 1994 Jul, 21(6), 438 - 40
The antibacterial and anti-staining properties of the novel anti-adherent agent M239, 144 alone and in combination with chlorhexidine; Wade WG et al.; The anti-adherent agent M239,144 has been shown to reduce the adhesion of S . sanguis strains to saliva-coated hydroxyapatite by 27-94% . The purpose of this study was to determine any antibacterial properties of M239,144 which might inhibit replication of the organisms which do adhere and to determine whether M239,144 interferes with the antibacterial properties of the antiseptic agent chlorhexidine . Maximum inhibitory dilutions (MIDs) were calculated using both broth and agar methods . 0.1% M239,144 displayed no antibacterial activity against S . oralis NCTC 7864 or S . sanguis NCTC 7863 using the broth dilution method and had no antibacterial activity against a range of plaque-forming organisms using the agar dilution method . The anti-bacterial activity of chlorhexidine against four of five oral plaque-forming species was reduced by 0.1% M239,144 . The effect of a novel anti-adherent agent, MK239,144, on chlorhexidine staining was assessed in an in vitro model . 1% M239,144 completely prevented chlorhexidine staining at concentrations from 0.0002% to 0.2% . M239,144/chlorhexidine formulations show potential for a non-staining anti-plaque mouthwash.

Support Care Cancer, 1994 Jul, 2(4), 259 - 65
Amikacin and ceftazidime as empirical antibiotic therapy in severely neutropenic patients: analysis of prognostic factors; Rossini F et al.; This study aimed to evaluate the efficacy of amikacine and ceftazidime as an empirical antibiotic therapy for neutropenic patients affected by haematological neoplasms and to investigate the presence of prognostic features suggesting a poor outcome with this antibiotic combination at the onset of infection . This could allow the identification of subgroups of patients with a low rate of response to amikacin/ceftazidime therapy; in these patients different initial empirical therapy may be indicated . The study population comprised 166 severely neutropenic (absolute neutrophil count below 500/microliters) oncohaematological patients with fever or clinical signs of infection . Multivariate analysis confirmed four negative prognostic factors: 3 or more days of hospitalization at the onset of an infectious episode, a diagnosis of acute myelmany factors are present, cases can be stratified into three groups, of significantly different prognosis: favourable (0 or 1 factor) 76% success; intermediate (2 factors) 52% success; unfavourable (3 or 4 factors) 19% success . At the onset of an infectious episode a subgroup of patients with a very low response rate to empirical amikacin/ceftazidime antibiotic therapy is identifiable, for whom a different therapy is indicated . Because of the high rate of proven or probable fungal infections in this group, the immediate administration of a systemic antifungal therapy, in addition to antibacterial agents, could be considered in these high-risk patients . Studies should be specifically addressed to evaluating a stratification of empirical antibiotic therapy according to risk factors present at the onset of infection.

Pharmazie, 1994 Jul, 49(7), 512 - 6
Applicability of diffusion methods required by the pharmacopoeias for testing antibacterial activity of natural compounds; Brantner A et al.; The diffusion methods required by various pharmacopoeias were investigated in comparison to the bioautographic TLC assay in regard to the applicability and the statistical evaluation for testing the antibacterial activity of natural substances . Naringenin as an example for a weakly effective lipophilic natural compound and tetracycline as standard were used . Data were analysed by linear regression and ANOVA . The comparison of the disk diffusion method, the hole-plate diffusion method, and the bioautographic TLC assay showed that nature and amount of substance influence to a great extent the selection of the test method . The evaluation of parallelism demanded by the pharmacopoeias may provoke problems in comparing natural substances with strongly effective antibiotics . The simultaneous influence of different variables was examined with the help of ANOVA . The bioautographic TLC assay showed for spotted compounds a comparable reproducibility and accuracy to the diffusion methods mentioned above.

J Infect Dis, 1994 Jul, 170(1), 157 - 64
The individual microbiologic effect of three antimycobacterial agents, clofazimine, ethambutol, and rifampin, on Mycobacterium avium complex bacteremia in patients with AIDS; Kemper CA et al.; The individual antibacterial activities of clofazimine, ethambutol, and rifampin in the treatment of Mycobacterium avium complex bacteremia in patients with AIDS were determined . Sixty human immunodeficiency virus 1-infected patients who had at least one blood culture positive for M . avium complex were randomized to receive either clofazimine (200 mg), ethambutol (15 mg/kg), or rifampin (600 mg) once daily for 4 weeks . Only ethambutol resulted in a statistically significant reduction in the level of mycobacteremia . The median change in individual baseline colony counts was -0.60 log10 cfu/mL after 4 weeks of ethambutol (P = .046) . In contrast, median changes in individual baseline colony counts were -0.2 log10 cfu/mL and +0.2 log10 cfu/mL for clofazimine and rifampin, respectively (both, P > .4) . Ethambutol had greater antibacterial activity, as determined by changes in the level of mycobacteremia, than either rifampin or clofazimine, supporting its continued use in combination with other agents in the treatment of M . avium infection.

Biol Pharm Bull, 1994 Jul, 17(7), 927 - 30
Inhibitory activity on DNA gyrase and intracellular accumulation of quinolones: structure-activity relationship of Q-35 analogs; Ito T et al.; Q-35, 1-cyclopropyl-6-fluoro-1,4-dihydro-8-methoxy-7-(3- methylaminopiperidine-1-yl)-4-oxyquinoline-3-carboxylic acid, has excellent activity against gram-positive bacteria and inhibits S . aureus gyrase at concentrations more than 10-fold lower than those of other quinolones . In this paper, the effect of the C-7 and C-8 substituents of Q-35 on the inhibitory activity of gyrase purified from S . aureus, M . luteus, E . coli, and P . aeruginosa are described . In addition, intracellular accumulation of Q-35 was examined . The 50% inhibitory concentrations (IC50) of Q-35, 8-fluoro- Q-35, and 8-hydro-Q-35 on DNA gyrase purified from S . aureus were 2.5, 7.8, and 68 micrograms/ml, respectively . The IC50 on gyrase from P . aeruginosa were 11, 5.2, and 17 micrograms/ml, respectively . It is concluded that the introduction of a methoxy group into the 8 position of the quinolone leads to greater antibacterial activity against gram-positive bacteria . The concentrations of Q-35 which accumulated in S . aureus and E . coli were almost equal to ciprofloxacin, but in P . aeruginosa, Q-35 was lower than ciprofloxacin.

Vet Q, 1994 Jul, 16(2), 65 - 71
Bovine leukocyte adhesion deficiency--clinical course and laboratory findings in eight affected animals; Muller KE et al.; The clinical course of Bovine Leukocyte Adhesion Deficiency (BLAD) in eight Holstein Friesian cattle is described . Affected animals were presented with a history of poor thriving and recurrent bacterial infections . Five of these animals had to be killed because of severe respiratory disease shortly after admittance . Three affected animals survived calfhood only as a result of frequent antibacterial treatments . At one year of age, failure to thrive and stunted growth were still evident, but infections requiring antibiotic treatments occurred only sporadically . Clinical manifestations of BLAD were found in the digestive system (gingivitis, periodontitis, alveolar periostitis, diarrhoea), the respiratory system and the skin (impaired wound healing, chronic dermatitis) . A leukocytosis based on a mature neutrophilia, which persisted during infection-free periods, was observed in all animals . Granulocytes were substantially deficient of beta 2-integrin expression on their membranes . Anaemia, which was noted in four animals, may be related to the Anaemia of Inflammatory Disease Complex (AID) . The serum total protein content increased with time and was associated with elevated gamma-globulin levels . We suggest that, at a certain age, animals affected with BLAD are able to cope with environmental agents due to compensatory mechanisms of the immune system.

Antimicrob Agents Chemother, 1994 Jul, 38(7), 1496 - 500
Tight binding of clarithromycin, its 14-(R)-hydroxy metabolite, and erythromycin to Helicobacter pylori ribosomes; Goldman RC et al.; Clarithromycin is a recently approved macrolide with improved pharmacokinetics, antibacterial activity, and efficacy in treating bacterial infections including those caused by Helicobacter pylori, an agent implicated in various forms of gastric disease . We successfully isolated ribosomes from H . pylori and present the results of a study of their interaction with macrolides . Kinetic data were obtained by using 14C-labeled macrolides to probe the ribosomal binding site . Clarithromycin, its parent compound erythromycin, and its 14-(R)-hydroxy metabolite all bound tightly to H . pylori ribosomes . Kd values were in the range of 2 x 10(-10) M, which is the tightest binding interaction observed to date for a macrolide-ribosome complex . This tight binding was due to very slow dissociation rate constants of 7.07 x 10(-4), 6.83 x 10(-4), and 16.6 x 10(-4) min-1 for clarithromycin, erythromycin, and 14-hydroxyclarithromycin, respectively, giving half-times of dissociation ranging from 7 to 16 h, the slowest yet measured for a macrolide-ribosome complex . These dissociation rate constants are 2 orders of magnitude slower than the dissociation rate constants of macrolides from other gram-negative ribosomes . {14C}clarithromycin was bound stoichiometrically to 50S ribosomal subunits following incubation with 70S ribosomes and subsequent separation of the 30S and 50S subunits by sucrose density gradient centrifugation . These data predict that the lower MIC of clarithromycin compared with that of erythromycin for H . pylori is likely due to a faster rate of intracellular accumulation, possibly because of increased hydrophobicity.

Res Vet Sci, 1994 Jul, 57(1), 69 - 74
Pharmacokinetics of baquiloprim and sulphadimidine in pigs after intramuscular administration; Davies AM et al.; Baquiloprim, a novel 5-substituted 2, 4-diaminopyrimidine, has been developed specifically for veterinary use . It has been formulated as an injectable preparation and combined with sulphadimidine to exploit the synergistic activity of the two antibacterial agents . The formulation was given by deep intramuscular injection to pigs at doses of 10 mg kg-1 and 30 mg kg-1 and the pharmacokinetic properties were investigated . The in vitro activity of the two components was also determined against a range of porcine pathogens . Both components were rapidly absorbed and the maximum concentrations of 0.55 microgram ml-1 baquiloprim and 15.6 micrograms ml-1 sulphadimidine observed after the administration of the lower dose were well in excess of the minimum inhibitory concentration (MIC) values against susceptible pathogens, the highest combined MIC90 being 0.06 microgram ml-1 baquiloprim + 6.25 micrograms ml-1 sulphadimidine . Concentrations above the MIC values of most pathogens were maintained for more than 24 and 48 hours after the administration of the lower and higher doses, respectively . The volumes of distribution of 2.41 litre kg-1 observed after the lower dose and 4.60 litre kg-1 after the higher dose indicated that baquiloprim was well distributed and concentrated in tissues . These findings suggest that the formulation should be effective in the treatment of bacterial infections in pigs.

New Microbiol, 1994 Jul, 17(3), 203 - 10
PBP binding and periplasmic concentration as determinants of the antibacterial activities of three new oral cephalosporins in Escherichia coli; Cornaglia G et al.; The antibacterial activities of cefetamet, cefixime and cefuroxime were investigated in Escherichia coli with regard to their penetration rates through the outer membrane and their affinities for PBPs in Escherichia coli . The permeability coefficient of cefetamet was measured in E . coli C600 carrying a pUC18 plasmid derivative, in which the gene of a transferable cephamycinase (CMY-2) was cloned, whereas diffusion of cefixime and cefuroxime was measured in E . coli C600 harbouring the OXA-1 beta-lactamase gene . It was found that cefetamet penetrated 5 and 9 times faster than cefixime and cefuroxime, respectively . The correlation between antibacterial activities and PBP affinities was studied in E . coli C600 not producing beta-lactamases . In this strain, cefetamet and cefixime shared the same inhibitory activity (MIC = 1 microgram/ml for both antibiotics) and the same affinity for PBP 3 (ID50 = 0.25 micrograms/ml) . Cefuroxime had a lower inhibitory activity (MIC = 4 micrograms/ml) and a lower affinity for PBP 3 (ID50 = 0.5 microgram/ml) . Cefixime and cefuroxime had 20 and 10 times higher affinity, respectively, than cefetamet for PBP 1s . It was concluded that the superior PBP affinity of cefixime can counterbalance the better penetration of cefetamet through the outer membrane, whilst differences in either permeability or PBP affinity seem sufficient to explain the lower antibacterial activity of cefuroxime compared to cefixime, which might well be related to the poor stability of the cefuroxime molecule.

J Hosp Infect, 1994 Jul, 27(3), 201 - 8
Antibacterial activity of Actisorb Plus, Actisorb and silver nitrate; Furr JR et al.; Activated Charcoal Cloth with silver (Actisorb Plus) and solutions of silver nitrate, but not Actisorb (Activated Charcoal Cloth without silver), demonstrated antibacterial activity against Gram-negative and Gram-positive bacteria . This activity was unimpaired in the presence of plasma . Sodium thioglycollate was an effective neutralizer of Actisorb Plus and of silver nitrate, indicating that the release of silver from Actisorb Plus contributed to the antibacterial activity of the dressing.

Infect Control Hosp Epidemiol, 1994 Jul, 15(7), 484 - 7
Do nonclinical uses of antibiotics make a difference?
Young HK.
An increasing range of antibacterial compounds is being used for nonclinical purposes, especially in the fields of animal husbandry and fish farming . As in human medicine, exposure to antibiotics has lead to the emergence of antibiotic-resistant bacteria in animal populations . The potential impact of antibiotic use in animals on human health and the management of clinical infections in humans is discussed in light of growing evidence to suggest that "new" resistance genes and multiresistant pathogens with increased pathogenicity are emerging in food animals as a direct consequence of antibiotic exposure.

Clin Pharmacokinet, 1994 Jul, 27(1), 63 - 84
Intracellular concentrations of antibacterial agents and related clinical implications; Butts JD; Intracellular penetration, accumulation and disposition of antibacterial agents is crucial for effective treatment of infections caused by intracellular bacteria . Intracellular concentrations and locations of both antibacterials and bacteria remain poorly understood and further research is needed to establish the importance of these concepts . For example, concepts that have been shown to be important outcome predictors when applied to concentrations of antibacterial agents in the serum include: (i) the effect of the peak antibacterial serum concentration to minimum concentration inhibitory to 90% of organisms (MIC90) for bacteria; (ii) the effect of length of time the serum antibacterial concentration remains above the MIC90 curve; or (iii) the area under the MIC90 curve, but above the serum antibacterial concentration curve . Further research should determine whether or not these concepts have important applications in an intracellular environment . Intracellular pathogens have been increasingly contributing to respiratory infections in the community . Therefore, on the basis of intracellular activity against bacteria causing respiratory infections, macrolides are favoured as the most broad spectrum class of oral antibacterial agents available for the treatment of patients with community-acquired respiratory infections.

Clin Pharmacokinet, 1994 Jul, 27(1), 32 - 48
What is the evidence for once-daily aminoglycoside therapy?
Barclay ML, Begg EJ, Hickling KG.
Aminoglycosides are important antibacterial agents for the treatment of serious infection . Evidence suggests that high peak plasma concentrations must be achieved early in the course of treatment if these agents are to be effective, but prolonged high concentrations may cause ototoxicity and nephrotoxicity . Peak plasma concentrations of 6 to 10 mg/L and trough concentrations of less than 2 mg/L for gentamicin and tobramycin have been traditional goals of therapy . Extensive recent evidence from in vitro, animal and human studies suggests that these target concentrations need revision . Aminoglycosides display concentration-dependent bacterial killing, have a long postantibiotic effect, and induce adaptive resistance in Gram-negative bacteria . All of these factors support the use of larger doses of aminoglycosides that are given less frequently than conventional therapy . Studies in vitro support this approach, showing greater activity when aminoglycosides are given less frequently . Animal studies comparing different dosage intervals have shown varying results, with only a slight bias favouring the longer dosage interval . However, the short elimination half-lives for the drugs in animals limit the applicability of these models to humans . Importantly, there is convincing evidence in animal studies that nephrotoxicity and ototoxicity are both reduced when the same total daily dose is administered in less frequent doses . There have been at least 29 clinical trials comparing once-daily administration of aminoglycosides with conventional administration 2 to 4 times daily . In general, efficacy has not been shown to be different between regimens, although one trial showed an advantage for once-daily administration compared with administration 3 times daily . A small number of trials have shown less nephrotoxicity and ototoxicity with once-daily administration, leading several authors to suggest that there is sufficient evidence to warrant a change to once-daily administration of aminoglycosides . However, once-daily administration has not been well studied in the paediatric population, or in patients with renal failure or endocarditis, and cannot be recommended in these patients as yet . The choice of a 24-hour dosage interval is somewhat arbitrary, and the optimal interval may not necessarily be 24 hours . No studies have included dosage adjustment based on pharmacokinetic modelling methods, and the effect of this on treatment outcome needs to be assessed . The best method of administering aminoglycosides once daily is yet to be determined.

Ann Pharmacother, 1994 Jul-Aug, 28(7-8), 863 - 8
Mathematical examination of dual individualization principles (II): The rate of bacterial eradication at the same area under the inhibitory curve is more rapid for ciprofloxacin than for cefmenoxime; Goss TF et al.; OBJECTIVE: To compare two antibiotics at equal ranges of area under the inhibitory curve (AUIC) exposure to determine if the rate of bacterial eradication differed between these antibiotics . DESIGN: Retrospective comparison of two previously collected studies of similar patients with nosocomial pneumonia . SETTING: Hospitalized patients, most intubated in critical care units with nosocomial pneumonia . PARTICIPANTS: Patients treated with either i.v . ciprofloxacin (n = 74) or the i.v . third-generation cephalosporin cefmenoxime (n = 43) were compared for their length of treatment required to eradicate bacterial pathogens from their respective infection sites, using serial cultures from the site of infection . All patients were also assessed for clinical outcomes . Serum samples were obtained to evaluate individual patient antibiotic pharmacokinetics, which were used to model pharmacodynamics of response . The HPLC assay used for each antibiotic had interday coefficients of variation < 10 percent . Serum concentration versus time profiles were fit using the computer program ADAPT II to determine pharmacokinetic parameters for each patient . The primary drug exposure measure that related to response was the AUIC, calculated as steady-state AUC0-24/minimum inhibitory concentration . RESULTS: AUIC values in the patients ranged from 6.0 to more than 7000, yet the AUIC value was highly predictive of time to bacterial eradication (p < 0.001) . Although more than 75 percent of patients eventually achieved eradication of pathogens from tracheal aspirate cultures, ciprofloxacin and cefmenoxime differed significantly in the time required to sterilize these cultures . At appropriate AUIC values (> 250) for ciprofloxacin, the median time to eradication was two days, while cefmenoxime (also at AUIC values > 250) required six days to achieve the same result . CONCLUSIONS: We conclude that the more rapid in vitro bacterial killing, which is characteristic of ciprofloxacin at optimal AUIC values, can manifest in vivo as more rapid clearance of bacteria from the respiratory tract of patients, even when both agents are controlled for initial antibacterial exposure (i.e., same AUIC).

Farmaco, 1994 Jul-Aug, 49(7-8), 513 - 8
Antibacterial activity of metal complexes of benzil and benzoin thiosemicarbazones; Offiong OE et al.; The metal (II) complexes of benzyl and benzoin thiosemicarbazones have been synthesized and characterized . They were studied for their antibacterial, antifungal and amoebicidal activity in vitro and for their toxicity in vivo . The ligands and their metal complexes exhibited low antibacterial and amoebicidal activity . The metal chelates of benzoin thiosemicarbazone seem to be the most active compounds.

J Clin Gastroenterol, 1994 Jul, 19(1), 6 - 10
Antibacterial therapy of Helicobacter pylori-associated peptic ulcer disease: a new strategy . The Swedes go for it; Gad A et al.; A consensus meeting was held in Stockholm on Oct . 9, 1993, after consultations with the Swedish Association of Gastroenterology and Gastrointestinal Endoscopy . The meeting was attended by 35 physicians with a special interest in Helicobacter pylori-associated diseases representing the following medical disciplines: gastroenterology, surgery, internal medicine, histopathology, microbiology, immunology, infectious diseases, clinical physiology, and cancer epidemiology . The aims of the meeting were to define and recommend methods of diagnosis, indications for anti-H . pylori therapy, alternatives for treatment regimens, principles of follow-up observation, and suitable measures of quality control . The participants agreed to recommend anti-H . pylori therapy only for the treatment of H . pylori-associated gastric and duodenal ulcer disease . A combination of amoxicillin, 1,000 mg b.i.d., plus omeprazole, 20 mg b.i.d . for 2 weeks was considered the first-line treatment . Second-line options are not specified, but amoxicillin plus a higher-dose omeprazole, clarithromycin plus omeprazole, or various triple regimens were discussed.

Chem Pharm Bull (Tokyo), 1994 Jul, 42(7), 1442 - 54
Synthesis and structure-activity relationships of 7-{3-(1-aminoalkyl)pyrrolidinyl}- and 7-{3-1-aminocycloalkyl)pyrrolidinyl}-quinolone antibacterials; Kimura Y et al.; A series of 7-{3-(1-aminoalkyl and 1-aminocycloalkyl)-1-pyrrolidinyl} quinolones have been prepared and their biological properties evaluated . Among them, 1-(S)-aminoalkyl derivatives exhibited potent antibacterial activities against gram-positive and gram-negative organisms . They had moderate lipophilicity and high aqueous solubility compared to their aminomethyl counterparts; e.g., the 3-(1-aminoethyl)-1-pyrrolidinyl compound (83) showed superior pharmacokinetic properties to its aminomethyl counterpart (6).

Gematol Transfuziol, 1994 Jul-Aug, 39(4), 29 - 32
{Change in functional and metabolic activity of leukocytes and content of serum immunoglobulins of donor blood exposed to gamma radiation}; Nagoev BS; Changes in functional-metabolic activity of leukocytes and in donor serum immunoglobulin level in exposure to gamma radiation . B.S . Nagoev . Kabardin-Balkar University, Nalchik . The study of 40 samples of blood after 1-4 days of storage revealed a moderate significant reduction in concentrations of cation protein, in myeloperoxidase activity . In exposure to gamma radiation, there appeared dose- and intensity-related shifts in the blood elements morphology, inhibition of myeloperoxidase, in the content of leukocyte cation protein, serum immunoglobulins . These alterations in white blood morphological picture, inhibition of functional-metabolic activity of leukocytes and immunoglobulin unbalance during gamma radiation of isolated blood explain depression of immunobiological characteristics of the body in extreme conditions, particularly, the lack of antibacterial defense as a result of ionizing radiation.

Adv Dent Res, 1994 Jul, 8(2), 215 - 20
Food components and caries; Bowen WH; For many decades, sugars have been the dietary constituents receiving the most attention in relation to their effects on dental caries . Frequently, however, there is little relationship between the amount of sugar in a food and its ability to induce caries . Therefore, it is clear that constituents in the diet can influence the ability of plaque to lower the pH of sugar solutions . For instance, replacing sugar in foods with xylitol, sorbitol, saccharin, or aspartame may lead to a reduction in the incidence of dental caries . All these sugar substitutes are non-cariogenic, and some may possess cariostatic properties . The presence of arginine-rich proteins in the diet may provide a ready source of this amino acid, which is the substrate for the arginine deiminase pathway which can result in a rapid elevation of plaque pH values . Proline can act as an acceptor for protons from lactate in the Stickland reaction . This is a major but much-neglected metabolic pathway in dental plaque . The presence of fat in experimental diets has been shown to affect their cariogenicity . The effects have been ascribed to enhanced clearance of sugars from the mouth . It is also conceivable that several fatty acids express a potent antibacterial effect . The presence of calcium and phosphorus has been shown to influence the cariogenicity of foods; the effect, however, is restricted to the food containing the minerals . Evidence suggests that pyridoxine (vitamin B6) may exert a cariostatic effect by enhancing decarboxylation activity in dental plaque . It is clear that sugar alone is not the sole determinant of whether food is cariogenic . Furthermore, myriad substances may hinder or enhance the caries-promoting properties of sugars in the diet.

Stomatologiia (Mosk), 1994 Jul-Sep, 73(3), 35 - 7
{The use of demineralized bone brephomatrix in the plastic repair of different postoperative defects in the jaws}; Samsonov VE et al.; The aim of this research was assessment of the results of bone brephoplasty of the jaws . Bone tissue defects after cystectomy, granulectomy, and tooth removal were filled with fragmented transplant, demineralized osseous brephomatrix . Low-frequency ultrasound was used for antibacterial treatment of the recipient osseous bed . A total of 103 patients were operated on, brephoplasty was carried out in 60 . Demineralized osseous brephomatrix is characterized by excellent plastic and osteoinductive properties, due to which bone regeneration processes are completed 1.5-2 times sooner in comparison with the control.

Antibiot Khimioter, 1994 Jul, 39(7), 30 - 4
{Evaluation of the potential of chemotherapy of glanders caused by Pseudomonas mallei strains resistant to sulfanilamides and trimethoprim}; Manzeniuk IN et al.; A sulfanilamide resistant strain Ts-5 of Pseudomonas mallei was isolated in the experiments on sulfazine therapy of malleus . The spectrum and level of the strain cross resistance to sulfanilamides and trimethoprim were studied . The frequency of the SurTrr mutants of P . mallei was determined . Efficient antibacterial drugs for the therapy of malleus caused by the sulfanilamide resistant strain are recommended.

Indian J Physiol Pharmacol, 1994 Jul, 38(3), 207 - 10
A preliminary audit of practice--antibacterial prophylaxis in general surgery in an Indian hospital setting; Srishyla MV et al.; As a major proportion of antibacterials used in hospital practice are for surgical prophylaxis, an audit of practice in relation to antibacterial prophylaxis in general surgery was undertaken over a four week period in a teaching hospital to assess the extent to which principles governing surgical antibacterial prophylaxis were practised and to provide a feedback to the clinicians . The extent of use of anti-bacterial agents in surgical prophylaxis was 90% . The timing of administration was more than 2 h before surgery in 21% of the cases . Intravenous route was used in 97% of the cases . The duration of prophylaxis was more than 72 h in 48% of cases . Cefazolin was the most frequently prescribed either alone or in combination with metronidazole . The study indicated inappropriateness in the timing and duration of administration of surgical antibacterial prophylaxis.

J Biochem (Tokyo), 1994 Jul, 116(1), 53 - 8
Purification and molecular cloning of cDNA for an inducible antibacterial protein from larvae of the coleopteran, Tenebrio molitor; Moon HJ et al.; Antibacterial activity was induced in the hemolymph of larvae of the coleopteran Tenebrio molitor by injection of Escherichia coli . An antibacterial protein, named tenecin 1, was purified to homogeneity from the larval hemolymph and characterized . A cDNA clone for tenecin 1 was isolated and its complete sequence was determined . This protein was found to inhibit the growth of Gram-positive bacteria and to consist of 43-amino acid residues including six cysteine residues . The disulfide structure of tenecin 1 was determined by sequencing cysteine containing peptides obtained by digesting tenecin 1 with endopeptidase Lys-C, trypsin, and thermolysin . The amino acid sequence and its disulfide bonds were similar to those of sapecin and sapecin C, antibacterial proteins of Sarcophaga peregrina.

Phytochemistry, 1994 Jul, 36(5), 1287 - 91
Antibacterial trichorabdal diterpenes from Rabdosia trichocarpa; Osawa K et al.; Four antibacterial diterpenes, trichorabdals A, B, C and H were isolated from the leaves of Rabdosia trichocarpa and the relationship between their conformations analysed by spectroscopic and computational methods . Their antibacterial activity is discussed.

J Pharm Sci, 1994 Jun, 83(6), 887 - 92
X-ray structural studies and physicochemical characterization of the 1-butanol, 1-pentanol, and 1,4-dioxane solvates of succinylsulfathiazole; Bourne SA et al.; The crystal structures and thermal decomposition of three solvated forms of the antibacterial drug succinylsulfathiazole (SST) have been studied . The solvates, with 1:1 host-guest stoichiometry, are SST x 1-butanol (1) SST x 1-pentanol (2), and SST x 1,4-dioxane (3) . Solvates 1 and 2 crystallize in the triclinic system, space group P1, with two formula units per cell, and are nearly isostructural . The OH groups of the guest molecules in both solvates engage in hydrogen bonding to the host SST and occupy cavities in the crystals . Solvate 3 is triclinic, space group P1, with two formula units per cell, but the two independent solvent molecules are located in crystallographically distinct channels . In one channel, solvent molecules are hydrogen bonded to the host while, in the other, they are held by van der Waals interactions only . The structural results are in accord with thermogravimetric and differential scanning calorimetric data which indicate one-step desolvation for 1 and 2 but two-step desolvation for 3 . X-ray powder diffraction was used to attempt identification of the polymorphic forms of SST resulting from desolvation of 1-3 . Desolvation of 1 and 3 appears to yield pure polymorphs of SST while 2 yields a mixture of polymorphs . The activation energies for the desolvation of the nearly isomorphous solvates 1 and 2 were found by dynamic thermogravimetry to be 155 and 149 kJ mol(-1), respectively.

J Am Acad Dermatol, 1994 Jun, 30(6), 981 - 4
Cutaneous candidiasis as a cause of delayed surgical wound healing; Giandoni MB et al.; BACKGROUND: Reports in the literature of surgical wounds infected with Candida species are scant . OBJECTIVE: We describe a subset of patients with cutaneous candidiasis whose only clinical finding was delayed wound healing . METHODS: Surgical wounds managed with moist occlusive postoperative dressings were observed for delayed healing . RESULTS: Three patients are described who demonstrated delayed wound healing with failure to epithelialize . Fungal cultures from each patient revealed heavy growth of Candida . The problem resolved quickly with a modified wound care regimen and application of an antiyeast cream . CONCLUSION: Cutaneous candidiasis can be a cause of delayed wound healing, especially in surgical wounds treated with antibacterial ointments and occlusive dressings.

Antimicrob Agents Chemother, 1994 Jun, 38(6), 1433 - 8
Activities of roxithromycin used alone and in combination with ethambutol, rifampin, amikacin, ofloxacin, and clofazimine against Mycobacterium avium complex; Rastogi N et al.; Preliminary studies showed that roxithromycin possessed significant in vitro activity against a variety of atypical mycobacteria such as the Mycobacterium avium complex, M . scrofulaceum, M . szulgai, M . malmoense, M . xenopi, M . marinum, and M . kansasii and rare pathogens such as M . chelonae and M . fortuitum . In this investigation, radiometric MICs of roxithromycin, ethambutol, rifampin, amikacin, ofloxacin, and clofazimine for 10 clinical isolates of the M . avium complex (5 each from human immunodeficiency virus {HIV}-positive and HIV-negative patients) were determined . Roxithromycin MICs against all the isolates were below the reported maximum concentration of drug in serum at the routine pH of 6.8, and the MICs were further lowered by 1 to 2 dilutions at a pH of 7.4 . In vitro enhancement of roxithromycin activity against all strains was further investigated by the previously established Bactec 460-TB method by combining the drugs at sub-MIC levels . Antibacterial activity of roxithromycin was enhanced in all 10 strains by ethambutol, in 3 strains each by rifampin and clofazimine, in 2 strains by amikacin, and in 1 strain by ofloxacin . In vitro screening of three-drug combinations showed that combinations of roxithromycin, ethambutol, and a third potential anti-M . avium drug (rifampin, amikacin, ofloxacin, or clofazimine) resulted in further enhancement of activity in 13 out of 20 drug combinations screened.

Farmaco, 1994 Jun, 49(6), 407 - 10
High performance liquid chromatographic analysis of quinolone antibacterial agents; Barbato F et al.; Eleven quinolone antibacterials have been analyzed by HPLC . The effects of different pH values and organic modifiers on chromatographic behaviour are discussed . Moreover the influence on separation mechanism of different counter-ions at various concentrations in the eluent has been investigated . Two different chromatographic methods have been selected, that allow the simultaneous analysis of quinolones containing or not a piperazinyl moiety, respectively.

Jpn J Antibiot, 1994 Jun, 47(6), 647 - 54
{Antibacteriological activities of arbekacin and vancomycin against strains of MRSA}; Ishii T et al.; The activities of arbekacin (ABK) and vancomycin (VCM) against MRSA were compared, and the results are as follows . 1 . In antibacterial activities (MIC value) against 142 strains of MRSA, MIC50 of ABK was two times less than that of VCM . MIC90's were both 1.56 micrograms/ml . 2 . ABK was also superior to VCM in bactericidal activities within a short time against 100 strains of MRSA . After 4 hours, 42 strains were killed to below 10(-2) by 2 MIC of ABK, but 6 strains were killed to 10(-2) by 4 MIC of VCM . 3 . Against the MRSA 1936 strain, neither ABK nor VCM was active, when an inoculum size of about 10(8) CFU/ml was used . At an inoculum size of 10(5) CFU/ml, ABK showed strong bactericidal activity in a dose dependent manner, while bacteria killing activity of VCM was time dependent . 4 . In experimental infections with the MRSA 1936 strain, ABK showed high bactericidal activity rapidly, and area of body that showed bacterial inhibition appeared to be large compared to that obtained with VCM . 5 . As to protection from MRSA infections, ABK was significantly superior to VCM in activities against 3 out of 4 strains of MRSA tested . ABK showed more pronounced efficacy when administered in a single dose than in divided doses . These results indicated that ABK would exhibit therapeutic efficacy in a short time.

Insect Biochem Mol Biol, 1994 Jun, 24(6), 547 - 55
Lipopolysaccharide-lipophorin complex formation in insect hemolymph: a common pathway of lipopolysaccharide detoxification both in insects and in mammals; Kato Y et al.; The formation of the lipophorin-lipopolysaccharide (LPS) complex in Bombyx mori hemolymph and its role in LPS detoxification were explored . LPS, an antibacterial protein inducer in insects, was injected into B . mori larvae . Analytical density gradient ultracentrifugation revealed that after injection the LPS peak shifts to a zone of lower density with time . The shifted peak was identified as the lipophorin-LPS complex . This complex formation was also achieved in an in vitro mixture of cell-free hemolymph and LPS at 25 degrees C but not at 1 degree C . The lipophorin-LPS complex had a significantly lower capacity to elicit the mRNA of cecropin B, an antibacterial protein . The biological activity of reextracted LPS from the complex was slightly reduced in the Limulus test and no structural modification was observed in sodium dodecylsulfate-polyacrylamide gel electrophoresis (SDS-PAGE) . These results suggested that the formation of lipophorin-LPS strikingly reduces the cecropin inducibility of LPS without any structural change in LPS . Similar serum lipoprotein-LPS complex formation and reduction of biological activities of LPS were also observed in mammals . We, therefore, suggest that the formation of the serum lipoprotein-LPS complex is a common pathway to inactivate LPS both in insects and in mammals.

FEMS Microbiol Lett, 1994 Jun 1, 119(1-2), 249 - 53
The membrane destabilising action of the antibacterial agent chlorhexidine; Barrett-Bee K et al.; The antibacterial agent chlorhexidine has long been used as an agent for medical antisepsis . This compound is a membrane active agent which probably has its major antibacterial action by interference with the function of cellular membranes . The results demonstrated an inhibition of oxygen utilisation by bacteria which was related to falls in cellular ATP levels . There was an effect on the outer membranes of Gram-negative bacteria which allowed the release of periplasmic enzymes . The inner membrane was not ruptured but its functionality was breached and there was an inhibition of active uptake of small molecules which did not appear to be related to cellular ATP levels.

Biochem J, 1994 Jun 1, 300 ( Pt 2), 567 - 75
Novel inducible antibacterial peptides from a hemipteran insect, the sap-sucking bug Pyrrhocoris apterus; Cociancich S et al.; Insects belonging to the recent orders of the endopterygote clade (Lepidoptera, Diptera, Hymenoptera and Coleoptera) respond to bacterial challenge by the rapid and transient synthesis of a battery of potent antibacterial peptides which are secreted into their haemolymph . Here we present the first report on inducible antibacterial molecules in the sap-sucking bug Pyrrhocoris apterus, a representative species of the Hemiptera, which predated the Endoptergotes by at least 50 million years in evolution . We have isolated and characterized from immune blood of this species three novel peptides or polypeptides: (i) a 43-residue cysteine-rich anti-(Gram-positive bacteria) peptide which is a new member of the family of insect defensins; (ii) a 20-residue proline-rich peptide carrying an O-glycosylated substitution (N-acetylgalactosamine), active against Gram-negative bacteria; (iii) a 133-residue glycine-rich polypeptide also active against Gram-negative bacteria . The proline-rich peptide shows high sequence similarities with drosocin, an O-glycosylated antibacterial peptide from Drosophila, and also with the N-terminal domain of diptericin, an inducible 9 kDa antibacterial peptide from members of the order Diptera, whereas the glycine-rich peptide has similarities with the glycine-rich domain of diptericin . We discuss the evolutionary aspects of these findings.

J Vet Pharmacol Ther, 1994 Jun, 17(3), 175 - 85
Effects of feed additives and veterinary drugs on aldosterone production and release by porcine adrenal cells in vitro; Jager LP et al.; The preparation of suspensions of porcine adrenocortical cells is described . Within the conditions adopted, the cell suspension responded to various agents as expected . It was possible to screen drugs (standard range 0.3-100 microM, incubation period 1 h) for actions on the production/release of aldosterone by the cortical cells using 1 microM deoxycorticosterone as substrate . Progesterone, pregnenolone or corticosterone were also used as substrates . Feed additives of the quinoxaline type induced a slowly developing inhibition of aldosterone production/release by the cell suspension, which was virtually irreversible . During the standard 1 h incubation period inhibitions of up to 22 +/- 2% of control were observed, which increased upon prolongation of the incubation by 2 h . With 100 microM cyadox the inhibition increased from 19 +/- 2% to 35 +/- 2% with prolonged incubation . Ten nitrofuran compounds exerted a more rapidly developing inhibition (by up to 79 +/- 1% of control) of aldosterone production/release, which was reversible . A submaximal inhibition with 10 microM furazolidone of 21 +/- 5% increased to 40 +/- 1% with longer incubation . The concentrations at which these compounds exerted this effect in vitro were well below the peak blood plasma concentrations encountered after administration of the drugs in therapeutic doses . Polyether-antibacterials/ionophores rapidly inhibited aldosterone production/release (to 26 +/- 1% of control) and this effect was completely reversible . The nitroimidazole compounds tested did not affect aldosterone production/release when deoxycorticosterone or progesterone were used as substrates . With use of corticosterone and to a lesser extent with pregnenolone as substrates a clear inhibition (to 73 +/- 3% of control) of aldosterone production was obtained . Amprolium in concentrations up to 100 microM, with deoxycorticosterone as substrate, did not induce a significant change in aldosterone production/release by the suspension of adrenocortical cells . In the same dose range tylosin and roxarsone induced a small but significant inhibition (by up to 10 +/- 3% of control) of aldosterone production/release, which was not dose-dependent . It is concluded that a wide range of growth-promoting drugs may be able to change aldosterone production/release in the animal.

Int J Pept Protein Res, 1994 Jun, 43(6), 573 - 82
Activity of two synthetic amphiphilic peptides and magainin-2 against herpes simplex virus types 1 and 2; Aboudy Y et al.; The in vitro antiviral activity of two amphiphilic synthetic peptides, modelin-1 (mod-1) and modelin-5 (mod-5), and of the natural antibacterial peptide magainin-2 (mag-2) against herpes simplex viruses type 1 (HSV-1) and 2 (HSV-2) were evaluated . The peptides were incubated with the virus, i.e . direct inactivation, and their effects examined by means of plaque reduction assay and/or reduction in virus yield . Only mod-1 displayed a strong antiviral effect against HSV-1 and HSV-2, with 50% effective dose (ED50) values of 4.6 and 4.1 micrograms/mL, respectively . Mag-2, mod-5 and a mixture of both had no significant inhibitory effect . Addition of mod-1 up to a concentration of 100 micrograms/mL to the culture medium had no significant cytotoxic effect on host vero cells, as measured by the trypan blue-exclusion method . It showed, however, considerable hemolytic activity against human red blood cells . Experiments including acyclovir (ACV) as a reference viral inhibitor indicated that the mode of action of mod-1 is different from that of ACV . In contrast to ACV, the peptide inactivates the virus following a very short incubation before vero cell infection, suggesting some kind of direct interaction of the peptide with the viral envelope, rather than inhibition of viral DNA replication or gene expression . Our results suggest that mod-1 may be an effective topical antiviral agent against herpes viruses.

J Pharmacokinet Biopharm, 1994 Jun, 22(3), 207 - 27
Prediction of brain delivery of ofloxacin, a new quinolone, in the human from animal data; Kawakami J et al.; We attempted to predict the delivery of ofloxacin (OFLX), a new quinolone antibacterial agent (NQ), into cerebrospinal fluid (CSF) in the human based on the physiological properties and pharmacokinetic parameters of NQs in various animals . Physiological properties for evaluation of drug delivery into CSF such as volume and the bulk flow rate of CSF and weight of choroid plexus, were compared among the rat, rabbit, cat, dog, and human . Statistically significant correlations with power values of 0.82-0.89 in the linear regression were observed on log-log plots between brain weight and those properties of each species . Delivery of OFLX into CSF from blood was analyzed by "diffusion and flow model" with unidirectional efflux process from CSF to blood . The blood-CSF diffusion clearance and the efflux clearance of OFLX in the human were extrapolated from animal data based on the allometric correlations between brain weight and these parameters in the rat, rabbit, and dog . The apparent volume of distribution and the total body clearance of NQs in the human could also be predicted from animal data based on the classical Adolph-Dedrick approach . To simulate the CSF concentration-time profile of OFLX in the human by using these predicted parameters, it was necessary to consider both the lumbar CSF compartment and the ventricular CSF compartment . Both plasma and CSF concentration-time profiles of OFLX predicted from only animal experimental data were in good agreement with those observed clinically.

What Is Activated Sludge?, What Is Botulism?, What Is MIC?, What Is Nitrification?, What Is Genome?, r, Bacteriology, c, Microbe, e, Microbes, r, Microorganism, c, Bacterium, o, Bacillus, o, Salmonella, r, Bacteriological, a, Escherichia coli, i, Yeasts, s, Denitrifying, r, Microbiological, c, Listeriosis, n, Ciprofloxacin, n, Corynebacterium, c, Cell cultures, e, Escherichia coli, i, Microbiological, o, Pseudomonas aeruginosa, s, Streptococci, e, Gram negative, e, Enterobacteriacea, c, Photobacteria, o, Vibriosis, n, Cell cultures, a, Escherichia coli

Scientific Publications - Work Done by Microbiology Reader Bioscreen C
Agricultural Microbiology Anaerobic Microbiology Antimicrobial Susceptibility Artificial Atmosphere Bioassay of Antibiotics Biofilm Microbiology Bioreactor Technology Biotechnology Cell Biology Clinical Microbiology Environmental Microbiology Experiments with Yeast	Fermentation Food Microbiology Functional Genomics Gene Technology Growth Media Development Growth Rate and Lag Time Industrial Microbiology Medical/Pharmaceutical Field Microbiological Assay Microbiological Research Microbiology of Cosmetics go to a specific theme...	Military Microbiology Molecular Microbiology Mutagenicity and Genotoxicity Oral Microbiology Patents Postantibiotic Studies Soil Microbiology Spore Microbiology Veterinary Microbiology Waste/Wastewater Treatment Water Microbiology Wine Microbiology

� 2005 Transgalactic Ltd (manufacturer of Bioscreen C software) | Privacy Statement | P.O. Box 1393, 00101 Helsinki, Finland, phone: +358 9 85172920, fax: +358 9 8749481, e-mail: microbiology@bionewsonline.com

Last modified: May 25, 2005