Br J Ophthalmol, 1997 Nov, 81(11), 949 - 52 Heparinised intraocular infusion and bacterial contamination in cataract surgery; Manners TD et al.; BACKGROUND/AIMS: Heparin in solution reduces bacterial adhesion to intraocular lenses and a lower incidence of postoperative endophthalmitis has been reported with the use of heparin coated lenses . The safety of adding low molecular weight heparin to the infusion fluid during routine cataract surgery was investigated . Any direct antibacterial effect was looked for by culturing anterior chamber fluid samples taken at the completion of surgery . METHODS: A randomised, double blind, controlled study of 111 patients undergoing routine cataract surgery . Low molecular weight heparin at a concentration of 5 IU/ml was added to the infusion fluid in the trial patients . Samples from the anterior chamber taken at completion of surgery were cultured . Twenty nine samples of sterile infusion fluid were also cultured as further controls . RESULTS: No complications were found in either group, and no difference in observed postoperative inflammation in each group . In the heparinised group (n = 55) bacterial contamination was found in 31% of samples, compared with 27% in the no heparin group (n = 56) (no significant difference) . CONCLUSIONS: There appears to be no direct antibacterial effect of heparin, and other possible mechanisms of action are discussed . Heparin avoids many of the drawbacks of traditional antibiotic prophylaxis and may have the potential to be a safe and effective addition to endophthalmitis prevention. Vestn Khir Im I I Grek, 1997, 156(6), 38 - 41 {New approaches in the surgical treatment of pyo-necrotic forms of tendovaginitis}; Konychev AV et al.; New trends in surgical treatment of purulent tendovaginitis of the hand are described on the basis of clinical data of 295 patients with purulent tendovaginitis and its complications . A sparing operation technique was used as well as the fractional bathing of the purulent focus and regional antibacterial therapy at the postoperative period . This method of surgical treatment resulted in a shorter first stage of inflammation, less risk of complications (dermatogenic contracture, limited mobility in the joints of the fingers and toes, trophoneurotic disturbances) and less influence of injurious factors on the tendon in the process of treatment. Biochem Biophys Res Commun, 1998 Feb 24, 243(3), 844 - 8 The orientation of norfloxacin bound to double-stranded DNA; Bailly C et al.; Norfloxacin is a widely used antibacterial agent that inhibits DNA gyrase . This fluoroquinolone drug has significant interaction with double-stranded DNA, as judged from absorption and circular dichroism measurements . The mode of binding of norfloxacin to a variety of DNAs and polynucleotides has been investigated by electric linear dichroism . In the presence of calf thymus DNA, the drug chromophore is significantly tilted with respect to the DNA axis . This molecular arrangement contradicts classical intercalation . The orientation of the quinolone drug varies depending on the sequence of the target DNA . Binding to alternating copolymers is largely preferred compared to the corresponding homopolymers . The drug interacts preferentially with poly(dG-dC).(dG-dC) rather than with the other polynucleotides . The deletion of the 2-amino group of guanine (G-->I substitution) or the addition of a methyl group on cytosine residues (C-->methyl-C substitution) affect the drug-DNA interaction . The results show that norfloxacin is capable of interacting with a variety of DNA sequences, possibly via both minor and major groove contacts. Scand J Immunol, 1998 Feb, 47(2), 146 - 51 Lack of polarized type 1 or type 2 cytokine profile in asymptomatic HIV-1-infected patients during a two-year bimonthly follow-up; Canaris AD et al.; The production of type 1 (interferon or IFN-gamma) and type 2 (interleukin or IL-4 and IL-10) cytokines by mitogen-stimulated peripheral blood mononuclear cells (PBMCs) obtained from asymptomatic human immunodeficiency virus-seropositive (HIV+) patients untreated with any antiviral, antibacterial or antimycotic drugs, and from healthy individuals, was evaluated by quantitative ELISA . Patients who were HIV+ were characterized by the absence of abnormal cytokine production . The level of each cytokine differed among individuals in the same group with intersubject variations greater for HIV+ patients than for healthy individuals . The longitudinal evaluation of IFN-gamma, IL-4 and IL-10 production showed intrasubject variations which were particularly marked in HIV+ patients . Accordingly, HIV+ patients and, to a lesser extent, healthy individuals were characterized by a wide spectrum of possible profiles, which were confined to type 0 phenotype . In HIV+ patients no correlation was found between each cytokine level and the number of CD4+ T cells, not even in those with a falling CD4+ T-cell count and clinical symptoms. Klin Med (Mosk), 1997, 75(11), 69 - 71 {Treatment of severe dysentery}; Shakhmardanov MZ et al.; The paper presents analysis of clinical efficacy of etiotropic drugs in severe Flexner's dysentery chosen by sensitivity of the causing agent, schemes of antibacterial drugs of choice in the treatment of this disease, principles of detoxication therapy . Use of bacterial biological drugs in combined treatment of dysentery is validated. J Biol Chem, 1998 Feb 6, 273(6), 3718 - 24 Conformation-dependent antibacterial activity of the naturally occurring human peptide LL-37; Johansson J et al.; The influence of ion composition, pH, and peptide concentration on the conformation and activity of the 37-residue human antibacterial peptide LL-37 has been studied . At micromolar concentration in water, LL-37 exhibits a circular dichroism spectrum consistent with a disordered structure . The addition of 15 mM HCO3-, SO42-, or CF3CO2- causes the peptide to adopt a helical structure, with approximately equal efficiency, while 160 mM Cl- is less efficient . A cooperative transition from disordered to helical structure is observed as the peptide concentration is increased, consistent with formation of an oligomer . The extent of alpha-helicity correlates with the antibacterial activity of LL-37 against both Gram-positive and Gram-negative bacteria . Two homologous peptides, FF-33 and SK-29, containing 4 and 8 residue deletions at the N terminus, respectively, require higher concentrations of anions for helix formation and are less active than LL-37 against Escherichia coli D21 . Below pH 5, the helical content of LL-37 gradually decreases, and at pH 2 it is entirely disordered . In contrast, the helical structure is retained at pH over 13 . The minimal inhibitory concentration of LL-37 against E . coli is 5 microM, and at 13-25 microM the peptide is cytotoxic against several eukaryotic cells . In solutions containing the ion compositions of plasma, intracellular fluid, or interstitial fluid, LL-37 is helical, and hence it could pose a danger to human cells upon release . However, in the presence of human serum, the antibacterial and the cytotoxic activities of LL-37 are inhibited. Infect Immun, 1998 Mar, 66(3), 1045 - 56 Enteric beta-defensin: molecular cloning and characterization of a gene with inducible intestinal epithelial cell expression associated with Cryptosporidium parvum infection; Tarver AP et al.; A growing body of evidence suggests that endogenous antibiotics contribute to the innate defense of mammalian mucosal surfaces . In the cow, beta-defensins constitute a large family of antibiotic peptides whose members have been previously isolated from the respiratory and oral mucosa, as well as circulating phagocytic cells . A novel bovine genomic clone with beta-defensin-related sequence {corrected} related to those of these alpha-defensins was isolated and characterized . The corresponding cDNA was isolated from a small intestinal library; its open reading frame predicts a deduced sequence of a novel beta-defensin, which we designate enteric beta-defensin (EBD) . Northern blot analysis of a variety of bovine tissues revealed that EBD mRNA is highly expressed in the distal small intestine and colon, anatomic locations distinct from those for previously characterized beta-defensins . EBD mRNA was further localized by in situ hybridization to epithelial cells of the colon and small intestinal crypts . Infection of two calves with the intestinal parasite Cryptosporidium parvum induced 5- and 10-fold increases above control levels of EBD mRNA in intestinal tissues . An anchored-PCR strategy was used to identify other beta-defensin mRNAs expressed in the intestine . In addition to that of EBD, several low-abundance cDNAs which corresponded to other beta-defensin mRNAs were cloned . Most of these clones encoded previously characterized beta-defensins or closely related isoforms, but two encoded a previously uncharacterized prepro-beta-defensin . Northern blot evidence supported that all of these other beta-defensin genes are expressed at levels lower than that of the EBD gene in enteric tissue . Furthermore, some of these beta-defensin mRNAs were abundant in bone marrow, suggesting that in enteric tissue their expression may be in cells of hematopoietic origin . Extracts of small intestinal mucosa obtained from healthy cows have numerous active chromatographic fractions as determined by an antibacterial assay, and one peptide was partially purified . The peptide corresponded to one of the low-abundance cDNAs . This study provides evidence of beta-defensin expression in enteric tissue and that the mRNA encoding a major beta-defensin of enteric tissue, EBD, is inducibly expressed in enteric epithelial cells . These findings support the proposal that beta-defensins may contribute to host defense of enteric mucosa. J Antimicrob Chemother, 1997 Dec, 40 Suppl A, 45 - 57 Pharmacokinetics and pharmacodynamics of oral grepafloxacin in patients with acute bacterial exacerbations of chronic bronchitis; Forrest A et al.; This analysis was designed to characterize the population pharmacokinetics and pharmacodynamics of oral grepafloxacin (OPC-17,116) in patients with acute bacterial exacerbations of chronic bronchitis (ABECB) . The study group included 76 patients (43 male, 33 female) between 23 and 81 years of age, who were part of a multicentre, randomized, double-blind, dose-response study . Patients were randomly assigned to receive oral regimens of grepafloxacin, 200, 400 or 600 mg, each administered once daily for 14 days . Plasma samples for drug assay (typically eight per subject; four samples on either day 3, 4 or 5, plus troughs on other clinic visit days), were obtained during treatment . Population pharmacokinetic analysis was accomplished using iterative two-stage analysis . Cultures and quantitative Gram stains from serial 24 h collections of sputum were used to determine the time (in days) taken to eradicate each bacterial strain . Population pharmacodynamic analysis was performed for three measures of antibacterial response: probability of bacteriological cure, probability of clinical cure, and time to eradication . Grepafloxacin plasma concentration profiles were best fitted by a pharmacokinetic model with first-order absorption following a lag time between administration of the dose and onset of systemic absorption . All three measures of response were strongly related to the 24 h AUIC (AUC/MIC) . At an AUIC of <75, the percent probability of clinical cure was 71%; at an AUIC of 75-175, it was 80% (P < 0.05) and at an AUIC of >175, it was 98% (P < 0.01) . In conclusion, antibacterial response for grepafloxacin in ABECB patients was highly related to AUIC; values of <75 appear inadequate and values of >175 were optimal. J Antimicrob Chemother, 1997 Dec, 40 Suppl A, 19 - 25 Antibacterial activity of grepafloxacin; Wiedemann B et al.; Grepafloxacin has an extremely broad spectrum of activity . Its activity against Gram-positive bacteria exceeds that of currently available quinolones . Grepafloxacin-resistant mutants seem to occur less frequently than ciprofloxacin- or ofloxacin-resistant mutants, and the increase in MIC against the former mutants is less than that of the latter . This applies only to the relative differences (in dilution steps); the absolute values are similar . Grepafloxacin kills Gram-positive bacteria at concentrations little above the MIC . Its pharmacodynamic profile against pneumococci is promising, favouring use of this drug for respiratory tract infections. Analyst, 1997 Nov, 122(11), 1379 - 81 Determination of trimethoprim in tissues using liquid chromatography-thermospray mass spectrometry; Cannavan A et al.; A method is described for the determination of the antibacterial drug trimethoprim in tissues . Minced tissue is homogenised with chloroform-acetone (1 + 1 v/v), filtered, and the filtrate evaporated to an oily residue using a rotary evaporator . The residue is redissolved in methanol-water-acetic acid (50 + 48.7 + 1.3 v/v) and any fats present are partitioned into hexane . The aqueous phase is analysed by liquid chromatography-thermospray mass spectrometry in positive mode with the protonated molecular ion at m/z 291 being monitored . Recoveries ranged between 60% in liver and 79% in muscle . The limit of determination was 25 micrograms kg-1 and the limit of detection was approximately 4 micrograms kg-1 . The method is suitable for monitoring tissues taken under national surveillance schemes for veterinary drug residues. Biomed Chromatogr, 1998 Jan-Feb, 12(1), 31 - 3 Comparative study of Scutellaria planipes and Scutellaria baicalensis; Zhang YY et al.; Scutellaria planipes, a species of Scutellaria, was explored by comparing to Scutellaria baicalensis, a pharmacopoeia species . Four principle flavonoids in both the plant roots were analyzed by using a reversed-phase chromatographic system with a chemically bonded ODS silica gel column and phosphate buffer:methanol (68:32 and 1:1) as mobile phase . Their contents were similar in both plant roots . Antiallergic and antibacterial activities in vitro and acute toxicity were compared . The results provided valuable data for S . planipes as a potential medicinal resource. J Immunol, 1998 Feb 15, 160(4), 1936 - 43 High dose intravenous immunoglobulin does not affect complement-bacteria interactions; Wagner E et al.; Pooled IgG preparations for i.v . use (IVIg) have been shown to possess anticomplementary activity in autoimmune and systemic inflammatory diseases . Both in vitro and in vivo, IVIg is a preferential acceptor of activated C4 and C3, thus diverting complement activation from the target surface . We explored the effect of IVIg on complement-bacteria interactions in an attempt both to determine the safety of IVIg preparations in relation to natural immunity to bacteria and to extend our knowledge of the physiologic mechanism of action of IVIg . Using both complement-sensitive and complement-resistant bacterial strains, we investigated the effect of IVIg on C3 binding to bacterial surfaces . In all cases, whether complement could be directly activated by bacteria through the classical or the alternative pathway, IVIg had no effect on the amount of C3 bound to bacteria . In addition, IVIg did not inhibit complement-dependent bacterial lysis . Interestingly, increasing concentrations of IVIg induced an increase in C1q binding, suggesting the presence of low affinity complement-fixing antibacterial Abs in certain preparations . Using serum samples from patients treated with IVIg, complement binding to and lysis of complement-sensitive bacterial strains were not modified as compared with normal controls and pretreatment samples, although a decrease in C3 binding to sensitized human erythrocytes was observed . Our data suggest that IVIg does not affect direct complement-bacteria interactions, although it is a potent agent to use for diversion of complement activation on sensitized target surfaces. Microbios, 1997, 91(366), 7 - 14 Suppression of the growth of six potentially-pathogenic mycobacteria by beta-lactam/beta-lactamase-inhibitors; Prabhakaran K et al.; Drug-resistant tuberculosis and opportunistic infections by mycobacteria in immunocompromised subjects are not readily controlled with the antimycobacterial drugs now available . beta-Lactam antibiotics, the most widely used antibacterial agents, are ineffective against mycobacteria since they synthesize beta-lactamases . The beta-lactam/beta-lactamase-inhibitor combinations are used at present to treat infections caused by other beta-lactamase-positive organisms . Six potentially-pathogenic mycobacteria: Mycobacterium avium, M . chelonei, M . haemophilum, M . microti, M . scrofulaceum and M . simiae, were cultured in 7H9 medium (containing Tween 80 and albumin, dextrose, catalase) at 37 degrees C for 10-14 days, with or without various concentrations (2-100 micrograms/ml) of ampicillin/sulbactam, amoxicillin/clavulanate and piperacillin/tazobactam . More than 50-80% inhibition of the mycobacterial growth was observed at drug levels of 40-100 micrograms/ml in the medium; the drugs were active even when the detergent (Tween 80) was omitted . Against four of the mycobacteria, ampicillin/sulbactam proved to be the most active . The beta-lactam/beta-lactamase-inhibitor combinations may be of use as rational therapeutic agents against mycobacterial infections. Eur J Biochem, 1997 Dec 15, 250(3), 630 - 7 Cell adhesion properties of hemolin, an insect immune protein in the Ig superfamily; Bettencourt R et al.; The isolation of antibacterial peptides from the giant silkmoth Hyalophora cecropia has opened the area of animal antibiotics {Boman, H . G . (1991) Cell 65, 205-207} and the study of insect immune genes has revealed striking similarities to many immune response genes in mammals {Hultmark, D . (1994) Nature 267, 116-117} . However, the molecules and mechanisms behind primordial immune recognition are not understood . One candidate for one such recognition molecule is hemolin, a 48-kDa immunoglobulin-related protein first isolated from H . cecropia, where it is up-regulated upon infection and secreted into the hemolymph . Hemolin was shown to bind to bacteria and to hemocytes, giving rise to changes in hemocyte adhesiveness and intracellular phosphorylation patterns {Faye, I . & Kanost, M . (1997) in Molecular mechanisms of immune responses in insects (Brey, P . T . & Hultmark, D., eds) Chapman and Hall, London} . In the present publication, we give evidence for the presence of a 52-kDa membrane form of hemolin on hemocytes, based on flow-activated cell sorting and membrane protein extractions . In addition we reveal calcium-dependent homophilic binding properties of hemolin, using hemolin-coated microspheres . When biotinylated recombinant hemolin was allowed to bind to hemocyte membranes, higher molecular-mass complexes were formed . Furthermore, we used immunological methods and Northern-blot analysis to demonstrate the presence of hemolin in embryos and retinal discs, suggesting that hemolin is expressed in several tissues at different developmental stages . These results show novel cell adhesion features of hemolin, corroborating its multifunctional character with putative roles in cellular and humoral immunity and in development. Acta Cient Venez, 1996, 47(4), 223 - 30 {Mechanism of phototoxicity induced by drugs}; Vargas F et al.; First of all some general concepts are given on phototoxic activity of pharmaceutical products which full fill the structural characteristics required to decompose by light and to cause biological damage, either themselves, their photoproducts or the products of their metabolism . These considerations are important due to the fact that this field of research is fairly new . Next, a review is given on recent research carried out in this laboratory on the photochemistry and phototoxicity of fibric acid and their derivatives and finally a review is made as well on the photochemistry and phototoxicity of antibacterial quinolones . Mechanisms are postulated for the photochemical decomposition of the substances investigated and possible mechanism for the in vitro activity at cellular level are also presented. Insect Mol Biol, 1998 Feb, 7(1), 51 - 62 In vivo regulation of tissue-specific and LPS-inducible expression of the Drosophila Cecropin genes; Roos E et al.; The inducible production of antibacterial cecropins in Drosophila fat body and haemocytes is controlled at the level of transcriptional induction . We demonstrate using germ-line transformation that a short, highly conserved, DNA region, including the insect kappaB motif, is necessary for tissue-specific expression in larvae and adults . Quantitative measurements of reporter gene activity in extracts from transgenic larvae confirmed the requirement of this proximal region for LPS-inducible expression in vivo . Transient expression in a blood cell line indicates the existence of positively acting elements further upstream of the conserved region . Furthermore, our in vivo data suggests that the distal upstream region contains negatively acting element(s). Helicobacter, 1997 Jul, 2 Suppl 1, S56 - 60 Primary gastric MALT lymphoma: trivial condition or serious disease? Genta RM, Graham DY. BACKGROUND: Primary gastric B-cell lymphomas originating from the mucosa-associated lymphoid tissue (MALT) have been demonstrated to be closely associated with Helicobacter pylori infection . Approximately 70% of these tumors regress within 1 year of eradication of H . pylori . Currently, there is little consensus on the best strategies for diagnosing, treating, and following up these lymphomas . Our objective was to review the current strategies for the diagnosis and management of MALT lymphomas and to describe the management guidelines used in our own institution . METHODS: Our approach consisted of a review of the literature and personal experience . RESULTS: Rigorous histopathological criteria (Isaacson's criteria) must be applied to the diagnosis of gastric biopsies with atypical lymphoid aggregates . Molecular and immunohistochemical studies might play have a role in determining the clonality of the lesions, but correlation with the histopathological aspects is crucial . CONCLUSIONS: Little solid information exists on the natural history and evolution of MALT lymphomas . While studies are being carried out, we suggest that even a suspected MALT lymphoma in a gastric biopsy specimen should be treated as a potentially serious condition . The diagnosis should be confirmed by an experienced histopathological laboratory, and H . pylori infection must be sought and treated . Because the response of lymphomas to antibacterial therapy cannot be predicted, close follow-up of affected patients is essential. Pol Merkuriusz Lek, 1997 Jul, 3(13), 5 - 7 {Activation of the antibacterial properties and neutrophil myeloperoxidase and acid phosphatase in patients with unstable angina pectoris}; Wysocka J et al.; Neutrophils are very important in pathogenesis of ischemic disease . They take part in the biomorphology of thrombus and also in the damage of myocardium ischemia in a course of unstable angina pectoris . We evaluated the functional status of neutrophils in peripheral blood, by measurement of bactericidal activity and activity of granulocyte's enzymes: myeloperoxidase (MPO) and acid phosphatase in the patients with unstable angina pectoris . We studied a group of 43 people at the age from 34 to 74 years . The blood for investigation was obtained during the first five hours from the moment of hospitalization . The control group were 40 healthy people . The number of granulocytes was significantly higher in patients with unstable angina pectoris and granulocytes were metabolically activated which was shown in the bigger activity of granulocyte's enzymes like MPO and acid phosphatase than in the control group . The activation of neutrophils is developed by many factors in the course of unstable angina pectoris . They take part in the processes of thrombogenesis and thrombolysis and they are a very important origin for active oxygen metabolites, which are responsible for damage of myocardium ischemia. Proc Natl Acad Sci U S A, 1997 Dec 9, 94(25), 13991 - 6 DNA topoisomerase targets of the fluoroquinolones: a strategy for avoiding bacterial resistance; Zhao X et al.; Fluoroquinolones are antibacterial agents that attack DNA gyrase and topoisomerase IV on chromosomal DNA . The existence of two fluoroquinolone targets and stepwise accumulation of resistance suggested that new quinolones could be found that would require cells to obtain two topoisomerase mutations to display resistance . For wild-type cells to become resistant, the two mutations must be acquired concomitantly . That is expected to occur infrequently . To identify such compounds, fluoroquinolones were tested for the ability to kill a moderately resistant gyrase mutant . Compounds containing a C8-methoxyl group were particularly lethal, and incubation of wild-type cultures on agar containing C8-methoxyl fluoroquinolones produced no resistant mutant, whereas thousands arose during comparable treatment with control compounds lacking the C8 substituent . When the test strain contained a preexisting topoisomerase IV mutation, which by itself conferred no resistance, equally high numbers of resistant mutants were obtained for C8-methoxyl and control compounds . Thus C8-methoxyl fluoroquinolones required two mutations for expression of resistance . Although highly lethal, C8-methoxyl fluoroquinolones were not more effective than C8-H controls at blocking bacterial growth . Consequently, quinolone action involves two events, which we envision as formation of drug-enzyme-DNA complexes followed by release of lethal double-strand DNA breaks . Release of DNA breaks, which must occur less frequently than complex formation, is probably the process stimulated by the C8-methoxyl group . Understanding this stimulation should provide insight into intracellular quinolone action and contribute to development of fluoroquinolones that prevent selection of resistant bacteria. Ned Tijdschr Geneeskd, 1997 Jun 28, 141(26), 1298 - 301 {Liver damage associated with the combination drug amoxicillin-clavulanic acid (Augmentin)}; de Haan F et al.; OBJECTIVE: To describe the case histories of patients with liver damage associated with the antibacterial combination amoxicillin-clavulanic acid . DESIGN: Descriptive . SETTING: University Institute for General Practice, Rotterdam, the Netherlands . METHOD: All reports (n = 40) of hepatic injury, attributed to amoxicillin-clavulanic acid (causal relationship 'possible', 'probable' or 'certain') and received by the Drug Safety Unit of the Inspectorate for Health Care since the registration of the combination (1982) until August 1996 were described and evaluated . RESULTS: The reports concerned 28 men and 12 women with an average age of 61 years who had used the drug mostly for a respiratory tract infection . The latency period between first in-take and onset of the reaction was 3 weeks on average . The mean duration of hepatic injury was approximately 6 weeks . The liver injury resolved fully . Five patients had had the reaction on more than one occasion . The main symptoms were jaundice, nausea, pruritus and abdominal pain . The pattern of hepatic injury was mostly cholestatic or mixed hepatocellular-cholestatic . CONCLUSION: Since liver damage to amoxicillin-clavulanic acid appears to be infrequent, this adverse effect is probably not caused by amoxicillin alone . The risk of liver damage to amoxicillin-clavulanic acid is highest in elderly patients treated with the combination on several occasions . Doctors should restrict the use of this combination to the treatment of infections with amoxicillin-resistant bacteria. Khirurgiia (Mosk), 1997, (7), 10 - 2 {Surgical tactics in prosthesis related vascular graft infections}; Lemenev VL et al.; The outcomes of treatment of patients with purulent wound complications and infection of vascular grafts after plastic surgery on terminal part of the aorta and major arteries of the lower extremities are analyzed depending on the tactics and timing of the surgery . Minimal lethality was registered in re-do surgery in the infected grafts performed in 2 or 3 stages, with the use of antibacterial prosthesis SISAN . This provides an opportunity to eliminate recurrence of infective complications. Clin Ter, 1997 Jan-Feb, 148(1-2), 23 - 8 {Prevention of bacterial and fungal infections in neutropenic patients with malignant hematologic diseases}; Candoni A et al.; Infections are a major cause of morbidity and mortality among immunocompromised patients . This report discusses bacterial and mycotic infections prophylaxis in the granulocytopenic patients with hematologic malignancies . Various strategies have been derived to prevent the infections: a combination of oral antibacterial and antifungal prophylaxis with quinolones and newer azoles (fluconazole, itraconazole), high efficiency particulate air filtration, protective isolation and management of central venous catheter . However, the emergence of antibiotic resistant organism continues to pose a major challenge to the successful eradication and prevention of infections in neutropenic host, and demands the development of innovative approaches to antibiotic use and infection control procedures. Lik Sprava, 1997 May-Jun, (3), 123 - 5 {The pharmacokinetics of Kefzol in patients with acute pancreatitis when administered intravenously and endolymphatically}; Pugaev AV et al.; Pharmacokinetics was studied of kefsole administered by intravenous and endolymphatic routes to patients (n = 23) with acute pancreatitis . The studies made showed that intravenous route for the drug administration makes for a quicker entering of the antibiotic into the peritoneal exudate . Apart from these reasons, endolymphatic antibacterial therapy does not appear to avert the development of complications involving pus-formation/discharging in acute pancreatitis and does not seem to be essential in the complex of therapeutic measures to be applied for treating the above patients. Klin Khir, 1997, (3-4), 86 - 8 {Multifactorial diagnosis and surgical treatment in inflammatory tumors of the uterine adnexa}; Dumanskii IuV et al.; In 66 patients with a tubo-ovarian tumor of inflammatory genesis in consequence of hyperdiagnostics in gynaecological compartments of general practice net diagnosis of the ovary cancer was established . Application of complex diagnostic measures, consisting of computing diagnosis tables construction, use of straight prolonged endolymphatic antibacterial therapy, ultrasonic investigation and computer tomography as well allowed to specify the diagnosis and to conduct an adequate surgical treatment. J Bacteriol, 1998 Feb, 180(3), 473 - 7 Mutational analysis of UMP kinase from Escherichia coli; Bucurenci N et al.; UMP kinase from Escherichia coli is one of the four regulatory enzymes involved in the de novo biosynthetic pathway of pyrimidine nucleotides . This homohexamer, with no counterpart in eukarya, might serve as a target for new antibacterial drugs . Although the bacterial enzyme does not show sequence similarity with any other known nucleoside monophosphate kinase, two segments between amino acids 35 to 78 and 145 to 194 exhibit 28% identity with phosphoglycerate kinase and 30% identity with aspartokinase, respectively . Based on these similarities, a number of residues of E . coli UMP kinase were selected for site-directed mutagenesis experiments . Biochemical, kinetic, and spectroscopic analysis of the modified proteins identified residues essential for catalysis (Asp146), binding of UMP (Asp174), and interaction with the allosteric effectors, GTP and UTP (Arg62 and Asp77). AIDS, 1998 Jan 1, 12(1), 65 - 74 Filgrastim prevents severe neutropenia and reduces infective morbidity in patients with advanced HIV infection: results of a randomized, multicenter, controlled trial . G-CSF 930101 Study Group; Kuritzkes DR et al.; OBJECTIVE: To assess the effect of filgrastim treatment on the incidence of severe neutropenia in patients with advanced HIV infection, and the effect of initial filgrastim treatment on prevention of infectious morbidity . DESIGN: Randomized, controlled, open-label, multicenter study . SETTING: Outpatient centers and physician offices . PATIENTS: Men and women aged > 13 years, who were HIV antibody-positive, and had a CD4 cell count < 200 x 10(6)/l, absolute neutrophil count (ANC) 0.75-1.0 x 10(9)/l, and platelet count > or = 50 x 10(9)/l within 7 days of randomization were eligible . Two hundred and fifty-eight patients entered and 201 completed the study . INTERVENTION: Daily filgrastim (starting at 1 microg/kg daily, adjusted up to 10 microg/kg daily) or intermittent filgrastim (starting at 300 microg daily one to three times per week to a maximum of 600 microg daily 7 days weekly) was administered to maintain an ANC between 2 and 10 x 10(9)/l . Patients in the control group received filgrastim if severe neutropenia developed . MAIN OUTCOME MEASURES: Incidence of severe neutropenia (ANC < 0.5 x 10(9)/l) or death, incidence of bacterial and fungal infections, duration of hospitalization and intravenous antibacterial use, and safety . RESULTS: The primary endpoint of severe neutropenia or death was less frequent in patients who received daily (12.8%) or intermittent (8.2%) filgrastim compared with control patients (34.1%; P<0.002 and P<0.0001 for comparison with daily and intermittent groups, respectively) . Filgrastim-treated patients developed 31% fewer bacterial infections and 54% fewer severe bacterial infections than control patients, required 26% less hospital days including 45% fewer hospital days for bacterial infections, and needed 28% fewer days of intravenous antibacterials . Filgrastim was not associated with an increase in HIV-1 plasma RNA level in a subset of patients in whom this was measured or any new or unexpected adverse events . CONCLUSION: Filgrastim was safe and effective in preventing severe neutropenia in patients with advanced HIV infection, and may reduce the incidence and duration of bacterial infections, incidence of severe bacterial infections, duration of hospital days for infections, and days of intravenous antibacterial agents. Wien Klin Wochenschr, 1997 Nov 14, 109(21), 830 - 5 {Aminoglycoside-induced nephrotoxicity}; Fabrizii V et al.; In severe gram-negative infections aminoglycosides generally remain the first-line antibiotic . Their use is limited by the high risk of side effects and, especially, nephrotoxicity . High peak levels are crucial for antibacterial activity, whereas toxic side effects are determined by the more prolonged trough levels . Thus, aminoglycosides should not be given by intramuscular injection because the peak levels achieved are inadequate, whilst long-lasting elevated plasma trough levels result . On administration of a daily single dose intravenously high antibacterial efficacy can be combined with low nephrotoxicity . Besides the dose-dependent bactericidal effect, the post-antibiotic effect of aminoglycosides is of importance . The main site of nephrotoxicity are the proximal tubule epithelial cells . Renal toxicity is usually reversible after discontinuation of drug therapy . Toxic acute renal failure is not uncommon (5-35%) and usually dependent on the underlying disease, preexisting renal function, hydration state, age, cumulative dose, additional medication, previous therapy with aminoglycosides and the choice of the specific aminoglycoside . By implementing a single daily dose regimen in conjunction with adequate hydration, alkalization therapy with bicarbonate, monitoring of plasma trough levels and minimization of the duration of therapy (5 days), development of renal impairment can be prevented in the large majority of patients . Hence, acute renal failure has become an avoidable, and much less frequently observed complication of aminoglycoside therapy due to these measures. Orv Hetil, 1997 Dec 21, 138(51), 3249 - 54 {Successful meropenem therapy of recurrent multiple brain abscess}; Schuller J et al.; Authors describe the history of a 37-year-old man suffering from multiple purulent brain abscess . The multiple brain abscess evolved primarily from a gluteal abscess to the lung, and secondarily from the lung to the brain by hematogenous spreading of the bacteria . The identification of the pathogene/s was unsuccessful despite numerous bacteriological examination . Despite many regimens of empiric antibacterial therapy the brain abscesses progressed, neurologic state of the patient deteriorated . At long last, the patient was given chloramphenicol . After that, he had no more fever, his consciousness cleared, no more epileptic convulsion occurred and the cell number of the cerebrospinal fluid became normal . The patient was thought to be cured and was sent home . Two months later fever occurred again and it was accompanied by excrutiating headache, increasing disorientation, so the patient was admitted to the hospital . The occurrence of a new brain abscess and purulent meningitis indicated the relapse of the disease . It was again unsuccessful to identify the pathogene/s therefore the authors treated the patient with many empiric antibiotic regimen, all of which-including chloramphenicol too--proved to be uneffective . As all the therapeutic regimens usually used in the treatment of purulent brain abscess were uneffective--including the combinations which have the widest antibacterial spectrum, authors gave meropenem as ultimum refugium . Some days later the fever came to an end, his consciousness cleared, the brain pressure and the cerebrospinal fluid became normal . The patient had no serious complaints in the course of the four years follow up, his residual neurologic symptoms regressed . On the base of this case history, authors suppose that meropenem--which has already proved to have a very wide antibacterial spectrum and to be very effective in the therapy of many kinds of serious bacterial infections--could also become a promising new therapeutic alternative in the treatment of purulent brain abscess. J Biol Chem, 1998 Jan 2, 273(1), 356 - 60 Solution structure of Der f 2, the major mite allergen for atopic diseases; Ichikawa S et al.; House dust mites cause heavy atopic diseases such as asthma and dermatitis . Among allergens from Dermatophagoides farinae, Der f 2 shows the highest positive rate for atopic patients, but its biological function in mites has been perfectly unknown, as well as the functions of its homologs in human and other animals . We have determined the tertiary structure of Der f 2 by multidimensional nuclear magnetic resonance spectroscopy . Der f 2 was found to be a single-domain protein of immunoglobulin fold, and its structure was the most similar to those of the two regulatory domains of transglutaminase . This fact, binding to the bacterial surface, and other small pieces of information hinted that Der f 2 is related to the innate antibacterial defense system in mites . The immunoglobulin E epitopes are also discussed on the basis of the tertiary structure. Biometals, 1998 Jan, 11(1), 27 - 32 Multiple parameters for the comprehensive evaluation of the susceptibility of Escherichia coli to the silver ion; Zhao G et al.; The susceptibility of Escherichia coli B to the antibacterial activity of silver ions was measured in terms of the initial inhibitory concentration, complete inhibitory concentration, postagent effect for bacteriostatic susceptibility, minimum bactericidal concentration, maximum tolerant concentration, and log killing time for bactericidal activity . At a concentration of 9.45 microM and an inoculum size of 10(4-5) CFU ml-1, silver caused growth delay of E . coli; at a concentration of 18.90 microM, silver completely inhibited bacterial growth . Prolonged postagent effects ranged between 1.5 and 12 h at 0.75 x the initial inhibitory concentration, 1.0 x the initial inhibitory concentration, and 1.5 x the initial inhibitory concentration of the silver ion . One log-unit of viable bacterial population size was lost every 30 min at the minimum bactericidal concentration of the silver ion . Silver tolerance was determined as 20 times the initial inhibitory concentration with 48 h of exposure . This study presents an evaluative model as a reference for the quantitative analysis of the susceptibility of bacteria to silver ions. J Chromatogr B Biomed Sci Appl, 1997 Nov 21, 702(1-2), 157 - 62 Rapid and simple determination of oxolinic acid and oxytetracycline in the shell of the blue mussel (Mytilus edulis) by high-performance liquid chromatography; Pouliquen H et al.; A simple procedure for the determination of oxolinic acid (OA) and oxytetracycline (OTC), two antibacterial agents, in the shell of the blue mussel (Mytilus edulis), using reversed-phase high-performance liquid chromatography is described . Liquid chromatography was performed on a 5-microm LiChroSpher 100 RP-18E column using acetonitrile and a 0.02 M orthophosphoric acid solution as the mobile phase, with ultraviolet detection . After roughly grinding the shell, drugs were extracted using a methanolic oxalic acid solution . Linearity and precision were checked over the concentration range 0.04-0.32 microg/g . Limits of detection of OA and OTC were 0.012 and 0.008 microg/g, respectively . Mean extraction recoveries of OA and OTC from mussel shell were 72.9 and 65.4%, respectively . To demonstrate the usefulness of the analytical procedure, an experimental study was performed in blue mussels exposed to the drugs for eight days. Acta Pol Pharm, 1997 Mar-Apr, 54(2), 135 - 40 Synthesis and antifungal activity of some new arylidenamino compounds; Ikizler AA et al.; A series of 3-alkyl/aryl-4-arylidenamimo-4,5-dihydro-1H-1,2,4- triazol-5-ones was synthesized and characterized by elemental and spectral analysis . These compound were tested for in vitro antibacterial and antifungal activity in solid agar cultures against eight microorganisms . In these test, some of the new compounds were shown to be very potent in vitro antifungal activity against the used fungi. Chemotherapy, 1998 Jan-Feb, 44(1), 21 - 30 In vivo antibacterial activity of a prodrug of NM394, a thiazetoquinoline carboxylic acid derivative; Ozaki M et al.; NM394 (6-fluoro-1-methyl-4-oxo-7-(1-piperazinyl)-4H-{1,3}-thiazeto {3,2-a}quinoline-3-carboxylic acid) has potent, broad-spectrum antibacterial activity in vitro, but not in vivo . To increase the bioavailability of NM394, various prodrugs were synthesized and tested . One of them, NM441, an N-(5-methyl-2-oxo-1,3-dioxol-4-yl) derivative, showed potent in vivo antibacterial activity . Using thin-layer chromatography-bioautography, we confirmed that after oral administration, NM441 was readily absorbed and hydrolyzed to NM394 . Other prodrugs of NM394 were only partially metabolized to NM394 . In pharmacokinetic studies in mice and monkeys, we found that the blood levels of NM394 were 7.8 and 5.9 times greater, respectively, when NM441 rather than NM394 was administered . These findings suggest that NM441 is an effective prodrug of NM394. Int J Pancreatol, 1997 Dec, 22(3), 215 - 20 Pure pancreatic juice from patients with chronic pancreatitis has an impaired antibacterial activity; Marotta F et al.; CONCLUSION: These data show that pure pancreatic juice of AICP patients has a markedly defective antibacterial activity . This finding might be of potential clinical interest in the understanding of the pathophysiology of the disease . BACKGROUND: The aim of the present study was to test the antibacterial activity of pure pancreatic juice in patients with chronic pancreatitis . METHODS: The study group consisted of ten patients with ethanol-induced chronic pancreatitis (AICP) and seven control patients free of pancreatic disease . All subjects had recently undergone a secretin-pancreozymin pancreatic function test . After an overnight fast, through a side-viewing endoscope, selective pancreatic duct cannulation was performed . After secretin stimulation, pure pancreatic juice was obtained . Three fractions of different molecular weights were separated . Samples were incubated with 1-mL suspension of 10(5) Escherichia coli ATCC 25,922, and log10 of colony-forming units were counted . Experiments were repeated by grading pancreatic juice concentration, pH of the medium, and inoculum size . RESULTS: No significant change of pH of pure pancreatic juice appeared between AICP and controls . Starting from 6-h observation, pure pancreatic juice of AICP patients showed a significant bacterial colonization vs controls (p < 0.01) . A direct correlation appeared between bacterial colonization and either pH and dilution of pancreatic juice (p < 0.001) . Antibacterial activity was independent of inoculum size, enzymatic activation or inhibition, and heat treatment . The fraction with 1000-10,000 molecular weight was the one endowed with antibacterial activity. Ceska Slov Farm, 1997 Jun, 46(3), 99 - 107 {Biological effects of substances similar to salicylanilides benzanilides}; Kubicova L et al.; The present review paper is the first collected communication about biological activity of benzanilides . The substances of the above-mentioned structures show a number of activities (antibacterial, ref . 1-22; antituberculous, ref . 23-25; antimycotic, ref . 26-95; antiviral, ref . 96-98, antiprotozoan, ref . 97; anthelmintic, ref . 37, 99-100; insecticidal, ref . 31, 37, 101-104; herbicidal, ref . 106-130, antitumour, ref . 131-137; immunosuppressive, ref . 134, 138; hypnotic, ref . 140; anticonvulsive, ref . 141-151, anti-inflammatory, ref . 152; local-anaesthetic, ref . 155-156; antiarrhythmic, ref . 155, 158; vasodilating, ref . 159; antiulcerative, ref . 160; anti-androgenic, ref . 161; hypoglycemic ref . 162) . Only very few of them have been hitherto introduced into practice . Papers investigating biological activity of benzanilides can be encountered also at present. J Antibiot (Tokyo), 1997 Mar, 50(3), 237 - 45 Novel C-2 substituted carbapenem derivatives . Part III . Synthesis and biological activity of 2-(functionalised ethenyl, oxyiminomethyl and alpha- Clear NJ, Davies JS, Eglington AJ, Fell SC, Hinks JD, Hird NW, Hunt E, Moss SF, Pearson MJ. The synthesis, antibacterial activity and stability to human dehydropeptidase-1 (DHP-1) of three small series of carbapenems carrying carbon-linked substituents at C-2 are described . C-2 Ethenyl carbapenems showed moderate antibacterial activity but poor stability to DHP-1 . C-2 Oxyiminomethyl carbapenems demonstrated variable activity and stability . C-2 alpha-(Hydroxy)benzyl carbapenems were the most promising and showed good potency and DHP-1 stability. J Antibiot (Tokyo), 1997 Mar, 50(3), 201 - 5 Production of brominated tiacumicin derivatives Hochlowski JE, Jackson M, Rasmussen RR, Buko AM, Clement JJ, Whittern DN, McAlpine JB. Several novel tiacumicin derivatives containing bromine have been produced by the addition of inorganic bromine to the fermentation broth of Dactylosporangium aurantiacum subsp . hamdenesis . Structures were elucidated employing mass spectrometry and NMR spectroscopy . Antibacterial activity of the bromotiacumicins is comparable to that of the parent compounds. Jpn J Cancer Res, 1997 Nov, 88(11), 1038 - 43 Lifestyle and anti-Helicobacter pylori immunoglobulin G antibody among outpatients; Hamajima N et al.; Since eradication of Helicobacter pylori (H . pylori) is thought to be a preventive measure against stomach cancer, several studies have examined factors associated with the infection . This paper reports the association of the infection with lifestyle factors observed in a hospital-based case-control study . Cases were 140 anti-H . pylori IgG antibody-positive outpatients (75 males and 65 females) . Controls were 52 antibody-negative outpatients (22 males and 30 females) . Both groups had undergone gastroscopy at Aichi Cancer Center Hospital between February 1995 and February 1997, and lifestyle data collected on the first visit were linked to calculate odds ratios . A strong association was observed with smoking among males; age-adjusted odds ratio (OR) = 7.85, 95% confidence interval (CI), 2.03-30.4 . Rice breakfast (OR = 3.74; 95% CI, 1.30-10.8) and soybean paste soup (every day vs . occasionally, OR = 5.24; 95% CI, 1.80-15.2) were also associated with antibody positivity in males, but not in females . In females, pickled Chinese cabbage (> or = 1/week vs . < or = 3/month, OR = 2.82; 95% CI, 1.06-7.48) and lettuce (> or = 1/week vs . < or = 3/month, OR = 2.90; 95% CI, 1.09-7.76) were significantly associated with positivity . Multivariate analysis gave similar estimates for the above factors . Although the association between smoking and H . pylori infection has not been detected in past studies of a general population, except one recent one, this study on outpatients suggested a possible association . Smoking may work as a cofactor disturbing incidental eradication of H . pylori by antibacterial agents administered for other reasons. Toxicol Pathol, 1997 Nov-Dec, 25(6), 635 - 43 Toxic effects of quinolone antibacterial agents on the musculoskeletal system in juvenile rats; Kashida Y et al.; Quinolone antibacterial agents have adverse effects on the musculoskeletal system in humans, consisting mainly of myalgia and arthralgia, and additionally of tendon disorders and rhabdomyolysis . The present study was conducted to examine the toxic effects of quinolones on the musculoskeletal system in juvenile rats using light microscopy, 5-bromo-2'-deoxyuridine (BrdU) immunohistochemistry and electron microscopy . Single oral administration of 900 mg/kg pefloxacin (PFLX) or levofloxacin (LVFX) was found to induce lesions in the muscle + fascia, tendon + sheath, and synovial membrane, in addition to articular cartilage in the fore- and hindlimbs . Articular cartilage lesions were not necessarily associated with changes in the muscle, tendon, and synovial membrane, or the reverse . Among all lesions, the ankle and elbow showed the highest incidence and severity . Changes were more severe in the PFLX than in the LVFX group . Lesions in the muscle + fascia, tendon + sheath, and synovial membrane were similar and characterized by edema and increased number of mononuclear cells, many of which were positively stained with BrdU, as well as vascular endothelial cells in the Achilles tendon sheath and synovial membrane in the ankle . Electron microscopic examination revealed an increased number of fibroblasts and macrophages and collagen deposition in the matrix of the synovial membrane and tendon sheath . Capillary endothelial cells were hypertrophied, increased in number, and stratified . These results suggest that quinolones have toxic potentials in the muscle, tendon, and synovial membrane in addition to articular cartilage, and that local vascular hyperpermeability may contribute to the development of these lesions. RNA, 1998 Jan, 4(1), 112 - 23 In vitro selection and characterization of streptomycin-binding RNAs: recognition discrimination between antibiotics; Wallace ST et al.; As pathogens continue to evade therapeutical drugs, a better understanding of the mode of action of antibiotics continues to have high importance . A growing body of evidence points to RNA as a crucial target for antibacterial and antiviral drugs . For example, the aminocyclitol antibiotic streptomycin interacts with the 16S ribosomal RNA and, in addition, inhibits group I intron splicing . To understand the mode of binding of streptomycin to RNA, we isolated small, streptomycin-binding RNA aptamers via in vitro selection . In addition, bluensomycin, a streptomycin analogue that does not inhibit splicing, was used in a counter-selection to obtain RNAs that bind streptomycin with high affinity and specificity . Although an RNA from the normal selection (motif 2) bound both antibiotics, an RNA from the counter-selection (motif 1) discriminated between streptomycin and bluensomycin by four orders of magnitude . The binding site of streptomycin on the RNAs was determined via chemical probing with dimethylsulfate and kethoxal . The minimal size required for drug binding was a 46- and a 41-mer RNA for motifs 1 and 2, respectively . Using Pb2+ cleavage in the presence and absence of streptomycin, a conformational change spanning the entire mapped sequence length of motif 1 was observed only when both streptomycin and Mg2+ were present . Both RNAs require Mg2+ for binding streptomycin. Yale J Biol Med, 1996 Nov-Dec, 69(6), 489 - 94 Effect of Thuya occidentalis on the labeling of red blood cells and plasma proteins with technetium-99m; Oliveira JF et al.; Thuya occidentalis is used in popular medicine in the treatment of condyloma and has antibacterial action . Red blood cells (RBC) labeled with technetium-99m (99mTc) are used for several evaluations in nuclear medicine . This labeling depends on a reducing agent, usually stannous ion . Any drug which alters the labeling of the tracer could be expected to modify the disposition of the radiopharmaceutical . We have evaluated the influence of T . occidentalis extract on the labeling of RBC and plasma proteins with 99mTc . Blood was withdrawn and incubated with T . occidentalis (0.25; 2.5; 20.5; and 34.1 percent v/v) . Stannous chloride (1.2 micrograms/ml) was added and then 99mTc was added . Plasma (P) and blood cells (BC) were isolated, also precipitated with trichloroacetic acid and soluble (SF) and insoluble fractions (IF) separated . The analysis of the results shows that there is a decrease in radioactivity (from 97.64 to 75.89 percent) in BC with 34.1 percent of the drug . In the labeling process of RBC with 99mTc, the stannous and pertechnetate ions pass through the membrane, so we suggest that the T . occidentalis effect can be explained (i) by an inhibition of the transport of these ions, (ii) by damage in membrane, (iii) by competition with the cited ions for the same binding sites, or (iv) by possible generation of reactive oxygen species that could oxidize the stannous ion. Immunopharmacol Immunotoxicol, 1997 Nov, 19(4), 425 - 36 Successful treatment of herpes simplex virus (HSV) recurrent genital infection with recombinant human (rh) granulocyte-macrophage colony stimulating factor (GM-CSF): a case report; Altamura M et al.; In the present work, we describe the treatment with rhGM-CSF of a woman affected by HSV recurrent genital infection and not responsive to specific antiviral therapy . The therapeutic regimen consisted of a subcutaneous administration of 300 mg/day of rhGM-CSF for six days . Before treatment with rhGM-CSF, polymorphonuclear cell and monocyte functional capacities and the antibacterial activity exerted by T cells were profoundly depressed . After treatment, a normalization of immune functions and a progressive disappearance of clinical manifestations were observed. J Altern Complement Med, 1997 Fall, 3(3), 249 - 56 A study of the changes in the bioactivity of essential oils used singly and as mixtures in aromatherapy; Lis-Balchin M et al.; The assumption by aromatherapists that essential oils are more beneficial when applied as mixes of two or more was tested using several in vitro bioactivity parameters . These included assays against 25 different bacteria, pharmacological studies using a smooth muscle preparation (guinea-pig ileum) and also the predicted effect on the patient as a whole on the basis of chemical analysis (using gas chromatography) . The results showed an enhancement in the antibacterial effect of some essential oils when used in mixes only when these were poor antibacterial agents on their own . The action on smooth muscle was often drastically changed when using mixes due to the combination of relaxant and contractile essential oils . A stimulant effect on patients was dependent almost entirely on a high monoterpene concentration . Due to the pharmacological changes achieved by mixing different essential oils, which cannot be predicted from animal studies, there is a possible danger in the indiscriminate usage of mixes on some susceptible patients, e.g., asthmatics and also during pregnancy and childbirth. Anesth Analg, 1998 Jan, 86(1), 159 - 65 The inhibitory effects of thiopental, midazolam, and ketamine on human neutrophil functions; Nishina K et al.; We investigated the effect of thiopental, midazolam, and ketamine (at clinically relevant concentrations and at 0.1 and 10 times these concentrations) on several aspects of human neutrophil functions . The three intravenous (i.v.) anesthetics significantly decreased chemotaxis, phagocytosis, and reactive oxygen species (ROS) (O2-, H2O2, OH) production of neutrophils in a dose-dependent manner . At clinically relevant concentrations, thiopental and midazolam significantly depressed these neutrophil functions . However, ketamine at the clinical plasma concentration did not impair chemotaxis or ROS production, except phagocytosis . In contrast, the three anesthetics had no effect on the levels of ROS production by a cell-free ROS generating system . In addition, intracellular calcium concentrations in neutrophils stimulated by N-formyl-L-methionyl-L-leucil-L-phenylalanine were dose-dependently decreased in the presence of each of the three anesthetics . The suppression of an increase in intracellular calcium concentrations may be responsible for the inhibition of neutrophil functions by the i.v . anesthetics . Implications: Neutrophils play an important role in the antibacterial host defense system and autotissue injury . We found that thiopental and midazolam (but not ketamine), at clinically relevant concentrations, impaired the neutrophil functions. Biochim Biophys Acta, 1997 Nov 20, 1354(3), 252 - 60 A series of meso-tris (N-methyl-pyridiniumyl)-(4-alkylamidophenyl) porphyrins: synthesis, interaction with DNA and antibacterial activity; Li H et al.; A series of meso-5,10,15-tris(N-methyl-4-pyridiniumyl)-20-(4-alkylamidophen yl) porphyrins were synthesized by derivatizing the amino group on the phenyl ring with the following hydrophobic groups: -C(O)C7F15, -C(O)CH=CH2, C(O)CH3, -C(O)C7H15, and -C(O)C15H31 . The cationic tris-pyridiumyl porphyrin core serves as a DNA binding motif and a photosensitizer to photomodify DNA molecules . The changes of the UV-Vis absorption spectra during the titration of these porphyrins with calf thymus DNA revealed a large bathochromic shift (up to 14 nm) and a hypochromicity (up to 55%) of the porphyrins Soret bands, usually considered as proof of porphyrin intercalation into DNA . Association constants (K) calculated according to the McGhee and von Hippel model, were in the range of 10(6)-10(7) M(-1) . An increase in hydrophobicity of the substituents at the 20-meso-position produced higher binding affinity . These porphyrins caused photomodification of the supercoiled plasmid DNA when a green laser beam at 532 nm was applied . Those with higher surface activity acted more efficiently as DNA photomodifiers . The porphyrin with a perfluorinated alkyl chain (-COC7F15) at the meso-20-position inhibited the growth of gram-positive bacteria (S . aureus, or S . epidermidis) . Other porphyrins exhibited moderate activity against both gram-negative and gram-positive organisms. Antimicrob Agents Chemother, 1997 Dec, 41(12), 2790 - 2 In vitro activities of new quinolones against Helicobacter pylori; Carbone M et al.; Compounds belonging to a new class of quinolones in which the fundamental C-6 fluorine atom was replaced were evaluated for in vitro antibacterial activity against 32 Helicobacter pylori strains . Since these substitutions resulted in higher inhibitory activities, these new desfluoroquinolones may be useful in eradicating H . pylori infections. Vestn Khir Im I I Grek, 1997, 156(4), 53 - 5 {The use of a perfluorocarbon emulsion in the local treatment of wounds complicated by a surgical infection}; Khrupkin VI et al.; The article shows effectiveness of the local application of Perftoran in complex treatment of purulent wounds of soft tissues in 50 patients . Perftoran has no necrolytic and antibacterial properties and fails to make the terms of the 1st phase of the wound process shorter . Perftoran maintains the intensified development of young cell elements at different periods of healing of the purulent wounds, decreases the propagation of microorganisms in them, lessens the wound square surface, results in earlier development of marginal epithelialization and formation of the elastic cicatrix. Haematologia (Budap), 1997, 28(4), 265 - 71 Successful outcome of aspergillus brain abscess in a patient who underwent bone marrow transplantation for aplastic anemia; Baslar Z et al.; We report the course of an aspergillus brain abscess in an 18-year-old female patient who underwent bone marrow transplantation for aplastic anemia . The abscess was discovered on day 35 post-transplant, in a cranial computerized tomography (CT) scan performed for the evaluation of an unexplained headache . Meanwhile, she was receiving broad-spectrum antibacterials and liposomal amphotericin B for a right upper pulmonary lobe infiltrate . A percutaneous puncture of the cerebral lesion was performed; fungal elements were seen in the pus obtained and its culture yielded A . fumigatus . The dose of amphotericin B was increased, intraconazole was added and two more punctures were done . With these antifungals, the abscess regressed significantly; so, amphotericin B was discontinued after a cumulative dose of 6775 mg but intraconazole was maintained at 400 mg/day . At the last follow-up, seventeen months after detection of the abscess, the patient was well, without symptoms and the cerebral lesion diminished to a very small, thick-walled CT image. Ostomy Wound Manage, 1997 Sep, 43(8), 26 - 30 Type of soap and the incidence of skin tears among residents of a long-term care facility; Mason SR; Skin tears are common among residents of long-term care facilities . This study evaluated the effectiveness of emollient antibacterial soap compared to non-emollient antibacterial soap in improving skin quality and reducing skin tears among residents of a long-term care facility . Skin tears were monitored over 4 months: non-emollient soap in the first and third months, and emollient soap in the second and fourth months were used . Rate of skin tears per resident per month were calculated . Incident reports were monitored the first month to establish skin tear rates using non-emollient soap . Skin tears decreased with the use of emollient soap (37% and 33% decrease in months two and four, respectively) and increased with the reintroduction of non-emollient soap (43% increase in month three) . Overall incidence of skin tears with the use of emollient soap was 34.8 percent lower than that of the non-emollient soap . Analysis of variance did not show statistical significance {F(1,84) = 3.108, p = .0821}, but clinical significance was demonstrated by the reduced number of skin tears with the use of emollient soap . While the etiology of skin tears seems to be a problem of aging, the decrease in skin tears in this study supports the continued use of emollient soap. Zhonghua Hu Li Za Zhi, 1997 Jun, 32(6), 316 - 9 {Nursing study of supporting aerosolized oxygen by combined drug liquid in children with intensive pneumonia}; Lian DH et al.; 148 cases of critical pneumonia at the same period were divided into two groups randomly and supplied by two oxygen therapeutic methods . The study group has 75 cases, whom were given aerosolized oxygen with antibacterial, antiphlogistic drugs, expectorants, antispastic and antiasthmatic drugs, and compared with 73 cases of convenient simple with aerosolized oxygen inhalation . The results showed the frequency, time and starting effect time of inhaling oxygen in two groups have significant difference (P < 0.001) and the alteration of SaO2 and the therapeutic effect in two groups also have significant difference (P < 0.05, P < 0.005 respectively) . The total effectual rates of the study and control group were 94.66% and 73.94% respectively . The difference between the duration of hospitalization and the therapeutic expenditure in two groups were significance (P < 0.01, P < 0.05 respectively) . The study indicated that aerosolized oxygen combined drug liquid is a better oxygen therapy method for treating pneumonia. Rev Prat, 1997 Oct 1, 47(15), 1655 - 60 {Vulvovaginitis}; Faure M et al.; Candidiasis, infection due to Trichomonas vaginalis and bacterial vaginosis (Gardnerella vaginalis and/or other species) represent the major three causes of vulvo-vaginitis . Other are rare bacterial infections and non infectious vaginitis such as allergic and post-menopausal vaginitis with epithelial atrophy . Clues for the diagnosis include the clinical features of vaginal discharge, cytological examinations, bacterial and fungal cultures . Only T . vaginalis seems to be responsible of sexually transmitted disease . All appropriate antibacterial or anticandidosic treatment are immediately effective, but the mechanisms of recurrent candidiasis and vaginosis are still unclear. J Antibiot (Tokyo), 1997 Oct, 50(10), 833 - 9 CJ-12,954 and its congeners, new anti-Helicobacter pylori compounds produced by Phanerochaete velutina: fermentation, isolation, structural elucidation and biological activities; Dekker KA et al.; Seven new phthalide compounds with anti-Helicobacter pylori activities were isolated from the basidiomycete Phanerochaete velutina CL6387 . The two most potent phthalide compounds, CJ-12,954 and CJ-13,014, have MICs of 5 ng/ml . The structure-activity relationship shows that the presence of a spiroketal part in addition to the phthalide part, greatly enhances the activity . The phthalide compounds appear to be specific for H . pylori, since they did not show antibacterial activities when tested against a panel of other microorganisms. Eur J Oral Sci, 1997 Oct, 105(5 Pt 2), 502 - 7 Chemical agents for the control of plaque and plaque microflora: an overview; Gaffar A et al.; This presentation provides an overview of the technologies available for the chemical control of plaque . It is generally accepted that the formation of dental plaque at the interfaces of tooth/gingiva is one of the major causes of gingival inflammation and dental caries . Several therapeutic approaches have been used to control dental plaque and supragingival infections . These include fluoride preparations such as stannous fluoride, oxygenating agents, anti-attachment agents, and cationic and non-cationic antibacterial agents . Among the fluoride preparations, stable stannous fluoride pastes and gels have been shown to reduce supragingival plaque, gingivitis, hypersensitivity and caries . The effect of the oxygenating agents on the supragingival plaque has been equivocal, but recent data indicate that a stable agent which provides sustained active oxygen release is effective in controlling plaque . A polymer, PVPA, which reduced attachment of bacteria to teeth was shown to significantly reduce plaque formation in humans . A new generation of antibacterials includes non-ionics such as triclosan, which in combination with a special polymer delivery system, has been shown to reduce plaque, gingivitis, supragingival calculus and dental caries in long-term studies conducted around the world . Unlike the first generation of agents, the triclosan/copolymer/sodium fluoride system is effective in long-term clinicals and does not cause staining of teeth, increase in calculus, or disturbance in the oral microbial ecology. FEBS Lett, 1997 Nov 3, 417(1), 135 - 40 Modulation of membrane activity of amphipathic, antibacterial peptides by slight modifications of the hydrophobic moment; Wieprecht T et al.; Starting from the sequences of magainin 2 analogs, peptides with slightly increased hydrophobic moment (mu) but retained other structural parameters were designed . Circular dichroism investigations revealed that all peptides adopt an alpha-helical conformation when bound to phospholipid vesicles . Analogs with increased mu were considerably more active in permeabilizing vesicles mainly composed of zwitterionic lipid . In addition, the antibacterial and hemolytic activities of these analogs were enhanced . Correlation of permeabilization and binding indicated that the activity increase is predominantly caused by an increased membrane affinity of the peptides due to strengthened hydrophobic interactions. APMIS, 1997 Nov, 105(11), 824 - 30 Normal interleukin-12 production in individuals with antibodies to Helicobacter pylori; Duchmann R et al.; It is increasingly recognized that the inability of the immune system to clear H . pylori infection is caused by an inadequate immune response and is associated with chronic gastric inflammation . To further investigate the cellular immune response to H . pylori, we studied PBMC from 31 H . pylori antibody-negative and 16 H . pylori antibody-positive individuals for H . pylori-induced DNA synthesis, secretion of the Th1-type cytokine IFN-gamma and secretion of IL-12, a cytokine produced by bacteria-stimulated monocyte/macrophages and a potent inducer of antibacterial immune responses and Th1-type T cells . All experiments were performed using Y . enterocolitica 03 as control . Our results demonstrate that DNA synthesis, IFN-gamma production and IL-12 production induced by H . pylori or Y . enterocolitica 03 did not differ significantly between H . pylori antibody-positive and H . pylori antibody-negative individuals . However, in the H . pylori-positive group there was a tendency, although not statistically significant, to produce less IFN-gamma in response to H . pylori but not Y . enterocolitica . These results demonstrate that monocyte/macrophages from H . pylori-positive individuals secrete normal amounts of IL-12 upon bacterial challenge and suggest that the decreased production of IFN-gamma in H . pylori-positive individuals observed in previous studies is selective for H . pylori and not caused by decreased IL-12 secretion. Plast Reconstr Surg, 1997 Dec, 100(7), 1855 - 66 Postoperative care following CO2 laser resurfacing: avoiding pitfalls; Weinstein C et al.; Facial skin resurfacing using the carbon dioxide laser has become an increasingly popular procedure . Improvements in carbon dioxide laser technology have made the procedure simpler and more reliable . However, difficulties in the postoperative period can lead to patient morbidity and physician anxiety . Common problems such as prolonged erythema, hyperpigmentation, acne, milia, dermatitis, and infection can be controlled or avoided with proper postoperative care . Less common sequela such as hypertrophic scarring and prolonged healing are often a results of errors committed in the postoperative period . The authors have performed laser resurfacing in almost 2100 patients in the last 4 years . Changes in the postoperative regimen to include no pretreatment, use of semipermeable dressings, antiviral and antibacterial prophylaxis, and early treatment with sunscreens and bleaching agents have made for a smoother recovery with more predictable results. J Nat Prod, 1997 Nov, 60(11), 1210 - 3 Antimycobacterial polyynes of Devil's Club (Oplopanax horridus), a North American native medicinal plant; Kobaisy M et al.; Two new (3 and 5), as well as three known (1, 2, and 4), polyynes were isolated from Devil's Club (Oplopanax horridus; Araliaceae), a medicinal plant of North America . The structures were established by 1H and 13C NMR . The absolute configurations of 2 and 5 were determined by application of Mosher's method . All the polyynes exhibited significant anti-Candida, antibacterial, and antimycobacterial activity, with an ability to kill Mycobacterium tuberculosis and isoniazid-resistant Mycobacterium avium at 10 micrograms/disk in a disk diffusion assay. Zhonghua Zheng Xing Shao Shang Wai Ke Za Zhi, 1996 Nov, 12(6), 437 - 9 {Evaluation of therapeutic effects of moist burn ointment and betadine ointment in treatment of severe burn}; Zheng S et al.; In order to compare the therapeutic value of moist burn ointment (MBO) and betadine ointment in severe burns, the authors divided 30 patients with burn over 30% TBSA into two groups . In one group MBO was used, and in another group betadine was used . The result showed; 1 . The difference between two groups was not great in superficial II degree burn wound . 2 . MBO was less effective than betadine in deep burn wound . MBO had little antibacterial effect, wound healing was delayed, and incidences of infection, complication and mortality were higher . At the same time, MBO did not have noticeable effect in inhibiting scar hypertrophy . The authors suggest that MBO must be used with caution in severe burn patients, especially in the southern provinces where the climate is hot and humid. Acta Odontol Scand, 1997 Oct, 55(5), 277 - 81 Surface ultrastructure of intact and in situ chlorhexidine-treated human buccal cells . A method for scanning electron microscopy; Vaahtoniemi LH; Air-dried and ethanol-fixed buccal epithelial cell smears from five subjects were observed by scanning electron microscopy . The mucous pellicle was precipitated as a smooth haze covering the cells, and outlines of bacteria were found embedded within it . Rinsing the preparations under running water gradually diminished the mucous pellicle but not the cell-adherent bacteria . A more complete dissolution of the pellicle was accomplished by washing the buccal epithelial cells before smearing . After a chlorhexidine mouthrinse the buccal cells appeared distorted, with only a few adherent bacteria . Three days after the rinsing, the denatured appearance still persisted on many cells, however, simultaneously with the emergence of undenatured epithelial cells with adherent bacteria . The method introduced in this study is useful to investigate the bacteria-mucus-epithelial cell interactions . A possible mode of antibacterial activity of chlorhexidine in vivo may be that it destroys bacterial adhesins . The substantivity of chlorhexidine in the oral cavity may be linked to the turnover rate of the oral epithelial cells. Leukemia, 1997 Nov, 11(11), 1807 - 12 Management of infective complications in patients with advanced hematologic malignancies in home care; Girmenia C et al.; A home care service has been implemented at our center with the aim of offering domiciliary assistance to patients with hematologic malignancies in advanced phase . We report our experience concerning the home management of these patients in the setting of infective complications . Of 151 patients in home care, 70 (46%) developed a total of 109 febrile episodes, performance status and neutrophil count significantly affecting the incidence of infections . Fever was of unknown origin in 51% of cases and microbiologically and clinically documented infections accounted for 26 and 23% of the cases, respectively . Oral ciprofloxacin in patients not neutropenic and intravenous ceftriaxone plus amikacin in neutropenic patients was shown to be effective and suitable for empiric home antibacterial treatment; in fact, 65% of febrile episodes responded to the initial antibacterial therapy with a further 16% after modification . Overall, 19.3% of the infective episodes were fatal, the prognosis appearing to be similar to that usually observed in the same category of patients in an inpatient setting . Our experience appears to show that a home care program could be the option of choice for patients with advanced cancer even in the setting of infective complications . It could improve the quality of life of patients and of their families, and it could save these subjects the risk of developing infections by resistant nosocomial isolates. Brain Res, 1997 Sep 12, 768(1-2), 224 - 32 Invertebrate proenkephalin: delta opioid binding sites in leech ganglia and immunocytes; Salzet M et al.; The leech Theromyzon tessulatum and the marine mussel Mytilus edulis immunocytes contain a mammalian-like proenkephalin molecule . The opioid precursor was purified by gel permeation chromatography, anti-Met- and Leu-enkephalin-affinity column separation and then by reversed-phase HPLC . The amino acid sequence analysis, determined by Edman degradation, enzymatic treatments and matrix assisted laser desorption time of flight . The structure of the leech proenkephalin material demonstrates considerable amino acid sequence similarity with amphibian proenkephalin (e.g . 25.4% with Xenopus laevis) but it is smaller, 15 kDa vs . 30 kDa . In contrast, Mytilus proenkephalin is not only larger (26 kDa) but it exhibits a higher sequence identity with guinea pig proenkephalin (50%) . Both of the invertebrate materials possess Met-enkephalin and Leu-enkephalin in a ratio of 3:1 for Mytilus and 1:2 in the leech . They also contain Met-enkephalin-Arg-Gly-Leu and Met-enkephalin-Arg-Phe sequences that are flanked by dibasic amino acid residues, demonstrating cleavage sites . Furthermore, using sequence comparison with bovine proenkephalin A (209-237), enkelytin (FAEPLPSEEEGESYSKEVPEMEKRYGGFM), an antibacterial peptide is found in the proenkephalin of both animals and it exhibits a 98% sequence identity with mammalian material . Finally, opioid binding experiments demonstrate the presence in leech ganglia and immunocytes of delta1 and delta2 opioid receptor subtypes as also found human and Mytilus immune cells . This report constitutes the first complete biochemical characterization of mammalian proenkephalin in invertebrates, demonstrating its origin in simpler animals. Biochim Biophys Acta, 1997 Oct 11, 1358(3), 255 - 60 Ribonucleases and host defense: identification, localization and gene expression in adherent monocytes in vitro; Egesten A et al.; Several ribonucleases of the RNase A family function as antibacterial, anti-parasitic and anti-viral agents . In this work, we have shown that mRNAs encoding five of the six known human ribonucleases of the RNase A family are expressed in cultured human monocytes, and that ribonucleases are released by adherent monocytes in culture . Using a polyclonal antiserum prepared against recombinant protein, we have detected one of these ribonucleases, RNase 4, in lysates of normal human peripheral blood monocytes, but not granulocytes or lymphocytes, by Western blotting . Subcellular localization by immunoelectron microscopy demonstrated the presence of RNase 4 in the cytoplasmic granules of isolated monocytes . Interestingly, mRNA encoding RNase 4 could not be detected in freshly isolated monocytes, emerging only after 16 h in culture, suggesting the possibility of de novo protein synthesis in association with monocyte differentiation. Anim Genet, 1997 Oct, 28(5), 367 - 9 Polymorphic sequence of Korean Native goat lactoferrin exhibiting greater antibacterial activity; Lee TH et al.; Lactoferrin, which exhibits antibacterial activity to protect infants from infectious disease, is a major component of colostrum and milk . Lactoferrin was purified from the colostrum of Korean Native goat, and the cDNA from the mammary gland mRNA of the animal was cloned and sequenced . The nucleotide sequence of the lactoferrin gene of Korean Native goat was found to differ in 15 sites from that of the goat lactoferrin gene reported earlier . This difference in nucleotide sequence resulted in six amino acid substitutions: five in the N-lobe and one in the C-lobe . The antibacterial activity of Korean Native goat lactoferrin was found to be greater than that of Sannen goat lactoferrin. Curr Opin Pulm Med, 1995 May, 1(3), 209 - 15 Respiratory infections following organ transplantation; Crawford SW; Successful organ transplantation often is limited by infection . The early transplant period is predominated by bacterial and fungal infections related to surgery and neutropenia, whereas opportunistic infections occur later due to long-term immunosuppression therapy . Despite technical differences between various types of organ transplants, the diagnostic approaches to lung disease are similar and rely largely on fiberoptic bronchoscopy . Whereas better antibacterial prophylaxis is available, fungal infections are emerging as significant problems . Lipid suspension formulations of amphotericin B and itraconazole offer new treatment options for fungal pulmonary infection . These formulations appear to have improved pharmacologic safety, but relative efficacy is unclear . Cytomegalovirus infections continue to plague transplant recipients . Improved understanding of the risk factors (especially the role of screened blood products) and improved prophylactic strategies with ganciclovir and immunoglobulin are decreasing the incidence of fatal infection . Surveillance for viremia and antigenemia now permit early identification of patients at significant risk for clinical disease, and responses to prompt administration of ganciclovir are encouraging, especially among solid organ recipients. Arch Pharm (Weinheim), 1997 Aug, 330(8), 268 - 70 Synthesis and antibacterial activities of new 1 beta-methylcarbapenems having a 1,3-diazabicyclo{3.3.0}octan-2,4-dione moiety; Nam KH et al.; The synthesis of a new series of 1 beta-methylcarbapenems having a 1,3-diazabicyclo{3.3.0}octane-2,4-dione moiety is described . Their in vitro antibacterial activities against both Gram-positive and Gram-negative bateria are determined and the effect of substituent on the bicyclic ring as well as stereoisomerism was investigated. Arch Pharm (Weinheim), 1997 Aug, 330(8), 237 - 41 Synthesis and biological investigations of pyrimidine derivatives; Cieplik J et al.; The study concerns new syntheses of 5-hydroxy ether and 5-aminohydroxy ether derivatives of pyrimidine . When tested for antibacterial activity, some of the compounds exhibited promising effects. Appl Environ Microbiol, 1997 Nov, 63(11), 4272 - 81 Degradation of the fluoroquinolone enrofloxacin by the brown rot fungus Gloeophyllum striatum: identification of metabolites; Wetzstein HG et al.; The degradation of enrofloxacin, a fluoroquinolone antibacterial drug used in veterinary medicine, was investigated with the brown rot fungus Gloeophyllum striatum . After 8 weeks, mycelia suspended in a defined liquid medium had produced 27.3, 18.5, and 6.7% 14CO2 from {14C}enrofloxacin labeled either at position C-2, at position C-4, or in the piperazinyl moiety, respectively . Enrofloxacin, applied at 10 ppm, was transformed into metabolites already after about 1 week . The most stable intermediates present in 2-day-old supernatants were analyzed by high-performance liquid chromatography combined with electrospray ionization mass spectrometry . Eight of 11 proposed molecular structures could be confirmed by 1H nuclear magnetic resonance spectroscopy or by cochromatography with reference compounds . We identified (i) 3-, 6-, and 8-hydroxylated congeners of enrofloxacin, which have no or only very little residual antibacterial activity; (ii) 5,6- (or 6,8-), 5,8-, and 7,8-dihydroxylated congeners, which were prone to autoxidative transformation; (iii) an isatin-type compound as well as an anthranilic acid derivative, directly demonstrating cleavage of the heterocyclic core of enrofloxacin; and (iv) 1-ethylpiperazine, the 7-amino congener, and desethylene-enrofloxacin, representing both elimination and degradation of the piperazinyl moiety . The pattern of metabolites implies four principle routes of degradation which might be simultaneously employed . Each route, initiated by either oxidative decarboxylation, defluorination, hydroxylation at C-8, or oxidation of the piperazinyl moiety, may reflect an initial attack by hydroxyl radicals at a different site of the drug . During chemical degradation of {4-14C}enrofloxacin with Fenton's reagent, five confirmatory metabolites, contained in groups i and iv, were identified . These findings provide new evidence in support of the hypothesis that brown rot fungi may be capable of producing hydroxyl radicals, which could be utilized to degrade wood and certain xenobiotics. Shock, 1997 Nov, 8(5), 349 - 56 Anti-interleukin-12 therapy protects mice in lethal endotoxemia but impairs bacterial clearance in murine Escherichia coli peritoneal sepsis; Zisman DA et al.; The overzealous production of proinflammatory cytokines in sepsis can result in shock, multiorgan dysfunction, and even death . In this study we assessed the role of endogenously produced interleukin (IL)-12 in murine models of endotoxemia and Gram-negative peritoneal sepsis . Initial studies indicated that intraperitoneal lipopolysaccharide (LPS) administration to mice induced a significant time-dependent increase in plasma, lung, and liver IL-12 levels . Passive immunization with anti-IL-12 serum intraperitoneally before LPS resulted in a marked reduction in plasma levels of tumor necrosis factor and interferon-gamma . Furthermore, we observed an increase in endotoxin-induced mortality in mice transiently overexpressing murine IL-12 using a recombinant adenoviral vector (Ad5 mIL-12) administered intraperitoneally . Neutralization of tumor necrosis factor or interferon-gamma in animals overexpressing IL-12 resulted in significant reductions in LPS-induced mortality, suggesting that the mechanism whereby IL-12 increases LPS-induced mortality is primarily mediated by the enhancement of these cytokines . In contrast, we observed no survival benefit in animals passively immunized with anti-IL-12 serum before the intraperitoneal administration of 2 x 10(8) live Escherichia coli . Interestingly, there was an approximately 70-fold increase in peritoneal fluid E . coli colony-forming units and the early onset of bacteremia in animals treated with anti-IL-12 serum, as compared with control animals . These results indicate that IL-12 is produced in response to LPS exposure, and the neutralization of this cytokine improves survival in endotoxin-challenged animals . However, IL-12 represents an essential component of antibacterial host defense, as anti-IL-12 therapy results in significant impairment in the host's ability to clear Gram-negative bacterial infection. J Antibiot (Tokyo), 1997 Sep, 50(9), 722 - 8 Ampullosporin, a new peptaibol-type antibiotic from Sepedonium ampullosporum HKI-0053 with neuroleptic activity in mice; Ritzau M et al.; Ampullosporin (I; Ac-Trp-Ala-Aib-Aib-Leu-Aib-Gln-Aib-Aib-Aib-Gln-Leu-Aib-Gln-Leuol) was isolated from the mycelium of Sepedonium ampullosporum as a new 15-membered peptaibol-type antibiotic . The structure was determined by mass spectrometric and two-dimensional NMR experiments . Ampullosporin displays narrow-spectrum antibacterial and antifungal activity, induces pigment formation by Phoma destructiva, causes hypothermia and decreased spontaneous locomotor activity in mice in dosages > 1 mg/kg. J Nat Prod, 1997 Oct, 60(10), 976 - 81 New steroidal alkaloids from Buxus longifolia; Atta-ur-Rahman et al.; Four new steroidal alkaloids, (+)-cyclovirobuxeine F (1), N-benzoyl-O-acetylbuxalongifoline (2), buxasamarine (3), and (+)-cyclobuxamidine (4), along with two known steroidal bases, 16 alpha-acetoxybuxabenzamidienine (5) and trans-cyclosuffrobuxinine (6), were isolated from the leaves of Buxus longifolia . The alkaloids 1-4 showed significant antibacterial activity. Pharmacol Res, 1997 Jun, 35(6), 557 - 60 Antibacterial activity of rifaximin reduces the levels of benzodiazepine-like compounds in patients with liver cirrhosis; Zeneroli ML et al.; Benzodiazepine-like compounds are present in trace amounts in the blood of normal subjects and increase in liver cirrhotic patients with or without encephalopathy . Their increased presence may, however, represent an occasional precipitating factor of hepatic encephalopathy . The source of these compounds is still unknown, but they are constituents of our diet since benzodiazepine receptor ligands have been described in plants, vegetables and in animals . They may also be synthesized, at least in part, by intestinal bacterial flora . In this article we report that the level of these compounds in the blood decreased by 40% after therapy with rifaximin, which reduces the aerobic and anaerobic intestinal bacterial flora . This observation indicates that intestinal bacterial flora is involved in the production of these compounds and that repeated short-term medications with this non-absorbable antibiotic may be useful in reducing the levels of benzodiazepine-like compounds in patients with liver cirrhosis. AJR Am J Roentgenol, 1997 Nov, 169(5), 1311 - 6 Hepatosplenic fungal disease: diagnostic accuracy and spectrum of appearances on MR imaging; Semelka RC et al.; OBJECTIVE: We describe our 6-year experience in the prospective examination of patients with suspected hepatosplenic fungal disease to show the diagnostic accuracy of MR imaging and the spectrum of appearances on MR images . SUBJECTS AND METHODS: All patients who underwent MR examination for suspected hepatosplenic fungal disease from January 1990 to January 1997 in three university institutions were included in the study . Patients presented with persistent fever or no response to antibacterial antibiotics . Patients were grouped as acute, subacute treated, and chronic treated, according to the duration of their symptoms . Patients with 2 weeks or fewer of possible infection were acute presentation, patients on antifungal therapy longer than 2 weeks but shorter than 3 months were subacute treated presentation, and patients on antifungal therapy for 3 months or longer or who had completed antifungal therapy and had a history of hepatosplenic fungal disease were chronic treated presentation . MR studies were prospectively interpreted for the presence of hepatosplenic fungal lesions . The appearances of fungal lesions in patients in each category were determined . The sensitivity, specificity, positive predictive value, negative predictive value, and accuracy for detecting lesions in patients with acute presentation were also determined . RESULTS: Sixty-nine patients were included in the study . MR imaging revealed signs consistent with hepatosplenic fungal lesions in 22 (32%) of 69 patients and no demonstration of hepatosplenic lesions in 47 (68%) of 69 patients . In the 60 patients with acute presentation, MR imaging in 13 patients revealed hepatosplenic lesions that were interpreted as fungal disease . True-positive lesions were present in 11 of these 13 patients . These lesions measured less than 1 cm in diameter and were best shown as well-defined high-signal-intensity foci on T2-weighted images . The remaining two of the 13 patients had false-positive lesions; one was shown to have tuberculosis, and the other had graft-versus-host disease . For acute presentation, MR sensitivity was 100%, specificity was 96%, positive predictive value was 85%, negative predictive value was 100%, and accuracy was 97% . In the five patients with subacute presentation, lesions were present that measured less than 1 cm in diameter and were best shown as mildly hyperintense on T1-weighted images . A perilesional ring nearly void of signal intensity was seen on unenhanced and gadolinium-enhanced T1-weighted images in all five patients . The four patients with chronic healed lesions all had lesions that were 1-3 cm in diameter with irregular, angular polygonal margins . These lesions, which were best shown on images obtained immediately after gadolinium administration, appeared as regions of diminished enhancement with no perilesional changes . CONCLUSION: MR imaging has high diagnostic accuracy for the diagnosis of acute hepatosplenic fungal disease . Patients with acute, subacute treated, and chronic healed presentations may have lesions that can be distinguished by their MR appearances. Infect Immun, 1997 Nov, 65(11), 4620 - 3 Chemokine secretion by human polymorphonuclear granulocytes after stimulation with Mycobacterium tuberculosis and lipoarabinomannan; Riedel DD et al.; Macrophages (MAC) and polymorphonuclear granulocytes (PNG) are professional phagocytes which perform essential functions in antibacterial defense . The intracellular bacterium Mycobacterium tuberculosis persists and replicates in resting macrophages . Although it is generally assumed that activated MAC are central to protection against M . tuberculosis, PNG may also contribute to defense . We wondered whether PNG produce proinflammatory chemokines after stimulation by M . tuberculosis or its major cell wall component, lipoarabinomannan (LAM) . In this study, we showed that M . tuberculosis- and LAM-activated human PNG secrete the leukocyte attractant interleukin-8 (IL-8) and the PNG-specific chemokine GRO-alpha in a dose-dependent manner . Treatment of PNG with the leukotriene-B4 inhibitor MK-886 prior to stimulation with M . tuberculosis or LAM partially blocked IL-8 and GRO-alpha induction, suggesting involvement of the 5-lipoxygenase pathway in the secretion of these chemokines . We conclude that PNG contribute to early resistance to M . tuberculosis via chemokine secretion. J Pept Res, 1997 Oct, 50(4), 279 - 85 Structure-antitumor and hemolytic activity relationships of synthetic peptides derived from cecropin A-magainin 2 and cecropin A-melittin hybrid peptides; Shin SY et al.; The hybrid peptide (CA-ME) derived from cecropin A(1-8) and melittin (1-12) has potent antibacterial and antimalarial activities . Because the N-terminal sequence 1-12 of magainin 2 is similar to melittin(1-12), CA-MA with CA(1-8) and MA(1-12) and their analogues were designed and synthesized . Antitumor activities of these peptides were evaluated using three small cell lung cancer cell lines . Greater antitumor activity was observed when the residues 16, 18 and 19 of the peptide were hydrophobic (Leu or Val), basic (Lys) and basic (Lys), respectively . The IC50 values of the peptides with the residues were 2 to 4 microM . Residue 12 was related to hemolytic activity rather than antitumor activity . Increase in amphipathicity of P4 enhanced hemolytic activity without significant change in antitumor activity . The alpha-helicity of the peptides in a 30 mM sodium dodecyl sulfate solution was more closely correlated to hemolytic activity than antitumor activity. Mol Microbiol, 1997 Sep, 25(6), 1159 - 66 Phage display selection of peptides against enzyme I of the phosphoenolpyruvate-sugar phosphotransferase system (PTS); Mukhija S et al.; The bacterial phosphoenolpyruvate-sugar phosphotransferase system (PTS) mediates the uptake and phosphorylation of carbohydrates and is involved in signal transduction . In response to the availability of carbohydrates it modulates catabolite repression, intermediate metabolism, gene expression and chemotaxis . It is ubiquitous in bacteria but does not occur in animals and plants . Uniqueness and pleiotropic function make the PTS a target for new antibacterial drugs . Enzyme I is the first component of the divergent protein phosphorylation cascade of the PTS . It transfers phosphoryl groups from phosphoenolpyruvate to the general phosphoryl carrier protein HPr . Six 15-mer, nine 10-mer and nine 6-mer peptides that inhibit enzyme I were selected from phage display libraries . Of these, 16 were synthesized and characterized . The majority of the peptides contain a histidine with an adjacent arginine . Two peptides were found to contain cysteines but no histidine . All peptides are rich in basic residues and lack acidic amino acids . The peptides inhibit the phosphotransferase system in vitro with IC50 of between 10 microM and 2 mM . Some, but not all, of the peptides inhibit cell growth in the agar diffusion test by an as yet undefined mechanism . All peptides are phosphorylated by enzyme I, and some are regenerated by slow autocatalytic hydrolysis of the phospho-peptide bond. J Intern Med Suppl, 1997, 740, 69 - 77 Empirical and subsequent use of antibacterial agents in the febrile neutropenic patient; De Pauw BE et al.; The objective of this analysis were an assessment of the feasibility of a more individually tailored approach of empirical antibiotic therapy in febrile neutropenia and an exploration of the reasons to modify the initial regimen . DESIGN, SETTING AND SUBJECTS: The main source was a database on febrile neutropenic cancer patients from an unblinded large trial conducted in 35 centres world-wide . This was supplemented by data from patients enrolled in a consecutive series of randomized trials at the Department of Haematology, University Hospital Nijmegen . INTERVENTIONS: Diagnostic procedures were standardized, types of possible infections defined and the reasons for modifying an empirical regimen were recorded . MAIN OUTCOME MEASURES: Survival of the febrile neutropenic episode, development of microbiologically and clinically defined infection in relation to causative organisms, and results of modification . RESULTS: Monotherapy was as effective as combination therapy with an overall mortality of < or = 7%, with 21% of neutropenic episodes accompanied by a clinically defined infection proving fatal compared with only 4% of episodes without a focus . At the end of treatment the empirical regimen had been added to in 60% of cases in the multicentre trial, in contrast to 39% in our own institution, in many cases simply because of continuing fever . CONCLUSION: The development of local guidelines for individually tailoring antibiotic therapy by complementing the empirical regimen is a feasible option for achieving an optimal anti-infective strategy for febrile neutropenic cancer patients. Med Klin (Munich), 1997 Jul 15, 92(7), 389 - 93 {Bactericidal permeability increasing protein (BPI-ANCA marked chronic inflammatory bowel diseases and hepatobiliary diseases}; Schnabel A et al.; BACKGROUND: Bactericidal permeability increasing protein (BPI) is an antibacterial product of neutrophilic granulocytes that can serve as target antigen for antineutrophil cytoplasmic antibodies (ANCA) . The clinical associations of autoantibodies against BPI (BPI-ANCA) are essentially unclear . PATIENTS AND METHODS: 587 sera from patients with chronic inflammatory bowel diseases, inflammatory hepatobiliary diseases, primary systemic vasculitides and other rheumatological diseases were examined for BPI-ANCA by mono-specific ELISA and a standard indirect immunofluorescence test for ANCA . (ACD-CPR versus S-CPR) . The treatment groups were similar with respect to age, sex, time interval from collapse to CPR, defibrillation and first epinephrine medication . There was no difference between the ACD group and the standard CPR group in terms of survival rates and neurologic outcome . No differences occurred concerning complications of CPR . CONCLUSION: In our two-tiered EMS system with physician-staffed ambulances ACD-CPR neither improved nor impaired the survival rates and the neurological prognosis in patients with out-of-hospital cardiac arrest . Our results are in accordance with other studies carried out in EMS systems, with first tier call-response intervals between 4 and 6 min . RESULTS: The prevalence of BPI-ANCA was 43% in ulcerative colitis, 23% in Crohn's disease, 35% in primary sclerosing cholangitis, 25% in primary biliary cirrhosis and 29% in autoimmune hepatitides . In a spectrum of systemic vasculitides, inflammatory joint diseases and collagen vascular diseases the prevalence was only 3 to 11% . In contrast to PR3-ANCA and MPO-ANCA, BPI-ANCA was not associated with a particular pattern of fluorescence in the immuno-fluorescence test on ethanol- and formalin-fixed neutrophils . CONCLUSION: This study shows that BPI-ANCA is the third ANCA specificity, besides PR3-ANCA and MPO-ANCA, with a limited spectrum of clinical associations . The diagnostic and prognostic relevance of BPI-ANCA in the above clinical conditions is being examined prospectively. Appl Environ Microbiol, 1997 Oct, 63(10), 4116 - 9 Inhibition of beta-galactosidase biosynthesis in Escherichia coli by tetracycline residues in milk; D'Haese E et al.; Low levels of tetracyclines found as residues in milk inhibited the biosynthesis of beta-galactosidase in Escherichia coli . To produce the same effect, other antibacterials had to occur in concentrations that were more than 10-fold higher . This relative selectivity was exploited for the development of a screening test for tetracyclines in milk based on a chemiluminometric assay of beta-galactosidase . The method was validated with spiked samples of raw milk and applied to field samples contaminated with tetracyclines. Blood, 1997 Oct 1, 90(7), 2796 - 803 The human antibacterial cathelicidin, hCAP-18, is synthesized in myelocytes and metamyelocytes and localized to specific granules in neutrophils; Sorensen O et al.; hCAP-18 is the only human member of the antibacterial and endotoxin-binding family of proteins known as cathelicidins . The antibacterial and endotoxin binding domains reside in the C-terminal 37 amino acids of the protein (LL-37) and this is believed to be unleashed from the neutralizing N-terminus by proteases from peroxidase positive granules . In human neutrophils, peroxidase positive and peroxidase negative granules can be subdivided into granule subsets that differ in protein content and ability to be exocytosed . To determine the localization of hCAP-18, we performed high-resolution immuno-electron microscopy and subcellular fractionation on Percoll density gradients . Biosynthesis of hCAP-18 was investigated in isolated human bone marrow cells . hCAP-18 was found to colocalize and comobilize with lactoferrin, but not with gelatinase in subcellular fractions . This was confirmed by electron microscopy . hCAP-18 is synthesized at the same stage of myeloid cell maturation as lactoferrin, and is efficiently targeted to granules . Like the peroxidase negative granule's matrix metalloproteinases, collagenase and gelatinase, hCAP-18 is also stored in unprocessed form . hCAP-18 is a major protein of specific granules where it is present in equimolar ratio with lactoferrin. Folia Biol (Krakow), 1996, 44(3-4), 87 - 94 Polydnaviruses of hymenopteran endoparasitoids knock out the host insect immune response; Glinski Z et al.; The insect immune system reacts against invading microorganisms and parasites with the recruitment of haemocytes and with humoral response . Cellular immune reactions involve phagocytosis, nodule formation and encapsulation by different types of haemocytes whereas insect cell-free antibacterial immunity depends on the production of a number of peptides and proteins, among which lysozyme, cecropins and attacins represent the major group of immune proteins . Polydnaviruses from certain hymenopterous parasitoids interfere with both host immunity and host development . These immunosuppressive viruses exhibit an intimate genetic relationship with the parasitoid since viral sequences are integrated within the parasitoid chromosomal DNA . The viral genes expression in parasitized host induces immunosuppression and alters development of the host insect . The parasitoids developing in the host body cavity knock out the insect immune system, inducing a decline in cellular and humoral components of the immune system so that parasitoid eggs are not recognized as foreign and thereby are not encapsulated . Polydnaviruses carrying parasitoids escape the host immune response and may develop within the insect host whereas other invaders are normally destroyed by defense factors of insect haemolymph. Khirurgiia (Mosk), 1997, (6), 56 - 61 {Antibiotic prophylaxis of postoperative infective complications in patients with rectal and colonic cancers}; Dmitrieva NV et al.; The results of operative use of clindamycin and netilmycin (1st group), piperacillin (2d group), in comparison to the standard protocol (carbenicillin and its combination with gentamicin) in 103 patients operated on rectal and colonic cancer are discussed . The rate of postoperative complications was 2.3% (1st groups), 5.3% (2d groups) vs . 37.1% (control group) . The authors advocate the proposed protocols of antibacterial prophylaxis of rectal and colonic cancer. Mol Cells, 1997 Aug 31, 7(4), 509 - 13 Hinnavin I, an antibacterial peptide from cabbage butterfly, Artogeia rapae; Bang IS et al.; We have previously isolated four antibacterial peptides from the immune haemolymph of the fifth instar larvae of cabbage butterfly, Artogeia rapae {Yoe, S . M., Bang, I . S., Kang, C . S., and Kim, H . J . (1996) Mol . Cells 6, 609-614} . They were induced by live, nonpathogenic gram negative bacteria . One of these novel antibacterial peptides was named hinnavin I . Hinnavin I is heat stable; its activity was retained after 60 min incubation at 100 degrees C, being effective against gram negative and/or gram positive bacteria . Hinnavin I and lysozyme II showed a powerful synergistic effect on the inhibition of bacterial growth . Amino acid composition was analyzed and the molecular weight was determined to be 4,139.94+/-10.91 Da by the ESI mass spectrometer . To elucidate the primary structure of hinnavin I, the amino acid sequence of this peptide was determined by N-terminal sequencing techniques . The amino-terminal half of the molecule was rich in charged amino acids and was hydrophilic, whereas the carboxyl-terminal half was hydrophobic. Keio J Med, 1997 Sep, 46(3), 115 - 9 Prevention of aminoglycoside-induced hearing loss; Sha SH et al.; This review discusses the current problem of ototoxicity associated with the worldwide use of aminoglycoside antibiotics . Pathology and pathophysiology of cochlear and vestibular damage have long been recognized as a preferential destruction of hair cells beginning in the cochlea with the outer hair cells of the lower turns . This is accompanied by high frequency hearing loss progressing to lower frequencies during and even after treatment with these drugs . A novel hypothesis of the underlying biochemical mechanism is based on the formation of free radicals by an aminoglycoside-iron complex . A protective treatment against aminoglycoside-induced hearing loss by co-administration of iron chelators has been successfully documented in guinea pig . This pharmacological intervention does not change serum levels of aminoglycosides nor their antibacterial efficacy . Since iron chelators are established therapeutic drugs, the proposed treatment should lend itself to clinical application . Aminoglycosides, long established for their high efficacy and low cost, may thus continue to play an important role in combating infectious diseases. Jpn J Antibiot, 1997 Aug, 50(8), 727 - 37 {Clinical efficacy in pediatrics sinusitis infections of cefditoren pivoxil granule therapy and its in vitro antibacterial activity against clinically isolated strains}; Sugita R et al.; We investigated the clinical efficacy in pediatrics sinusitis infections of cefditoren pivoxil granule therapy and its in vitro antibacterial activity against clinically isolated strains . The results are summarized as follows . The specimens from 343 patients were cultured and 595 strains of bacteria were isolated and identified . Oral doses of 3 and 5 mg/kg of CDTR-PI were clinically effective at high percentages, 85.1% and 89.5%, respectively, of treated patients . CDTR-PI at 3 mg/kg orally was clinically effective in 80.8% of patients with PCG intermediate S . pneumoniae (PISP) infections, 80.0% of those with PCG susceptible S . pneumoniae (PSSP) infections, 81.8% of those with H . influenzae infections and 78.3% of those with M . (B.) catarrhalis infections among the infections by major causative agents . The frequent isolates included S . pneumoniae accounting for 33.1%, H . influenzae accounting for 32.1%, M . (B.) catarrhalis accounting for 17.6% and S . pyogenes accounting 3.7% of all the isolates . PISP accounted for 16.1% of all the isolates and for 49.8% of the isolates of S . pneumoniae, and were isolated from 28.6% of the 343 patients . The isolation of PISP was frequent from children of 4 and under especially, and especially frequent from those below age 2 . Of the isolates of S . pneumoniae, the biotype frequencies among PSSP were in the order of type I > type II > type III, while those among PISP were in the order of type I < type II with none of type III . Bacteriologically, an eradication rate of 89.4% was achieved with 3 mg/kg and 93.5% with 5 mg/kg of CDTR-PI. Int Arch Allergy Immunol, 1997 Oct, 114(2), 111 - 5 Neutrophil-induced endothelial cell damage: inhibition by a 14-membered ring macrolide through the action of nitric oxide; Mitsuyama T et al.; Macrolide antibiotics have been used worldwide for about 40 years . The clinical effectiveness of oral erythromycin for diffuse panbronchiolitis has been established and erythromycin seems to act not only as an antibacterial but also as an anti-inflammatory agent . We investigated the effect of 14-membered ring macrolides, erythromycin and clarithromycin, on human neutrophil functions and endothelial cell damage induced by neutrophils . The superoxide production of neutrophils and Ca2+ influx into neutrophils induced by N-formyl-methionyl-leucyl-phenylalanine was inhibited by treatment with erythromycin but not by treatment with clarithromycin . When endothelial cells were cocultured with neutrophils, nitric oxide (NO) presumably released from endothelial cells were enhanced by treatment with erythromycin but not by treatment with clarithromycin and endothelial cell injury induced by neutrophils was ameliorated by addition of erythromycin but not by clarithromycin . The reduction of neutrophil-induced endothelial cell injury by erythromycin was abolished by treatment with carboxy-PTIO which traps NO in the medium . Moreover, nitrite in the medium in which endothelial cells were incubated with neutrophils was enhanced by treatment with erythromycin and the enhancement of nitrite by erythromycin was partially cancelled by addition of H-89, an inhibitor of cyclic AMP-dependent protein kinase (PKA) . Erythromycin seems to ameliorate neutrophil-induced endothelial cell injury by affecting not only neutrophil functions but the release of NO from endothelial cells through the action of PKA . The usefulness for the treatment of diseases worsened by the interaction between neutrophils and endothelium might be different among 14-membered ring macrolides. Am J Gastroenterol, 1997 Oct, 92(10), 1909 - 12 Ménétrièr's disease associated with Helicobacter pylori infection: resolution of enlarged gastric folds and hypoproteinemia after antibacterial treatment; Kawasaki M et al.; We herein report a case of a 46-yr-old female with Menetrier's disease associated with Helicobacter pylori (H . pylori) infection, in whom the appearance of enlarged gastric folds and hypoproteinemia were both successfully treated by antibacterial treatment . The patient had been treated with famotidine for 3 yr under a diagnosis of Menetrier's disease, which caused an increase in her serum protein concentration to a level at which she suffered no clinical problems; however, the concentration never reached a normal range, and the presence of enlarged gastric folds also remained unchanged . Because H . pylori colonization was detected in the stomach and was also retrospectively recognized in the initial histologic specimens, antibacterial treatment with omeprazole, clarithromycin, and metronidazole was thus attempted . As a result of the successful eradication of H . pylori, the enlarged gastric folds returned to normal and the serum protein concentration thus increased to a normal level after the treatment . The etiology of Menetrier's disease remains unknown; however, the above findings sugg