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Sample records for activate metronidazole nitroreductases

  1. Giardia, Entamoeba, and Trichomonas enzymes activate metronidazole (nitroreductases) and inactivate metronidazole (nitroimidazole reductases).

    PubMed

    Pal, Dibyarupa; Banerjee, Sulagna; Cui, Jike; Schwartz, Aaron; Ghosh, Sudip K; Samuelson, John

    2009-02-01

    Infections with Giardia lamblia, Entamoeba histolytica, and Trichomonas vaginalis, which cause diarrhea, dysentery, and vaginitis, respectively, are each treated with metronidazole. Here we show that Giardia, Entamoeba, and Trichomonas have oxygen-insensitive nitroreductase (ntr) genes which are homologous to those genes that have nonsense mutations in metronidazole-resistant Helicobacter pylori isolates. Entamoeba and Trichomonas also have nim genes which are homologous to those genes expressed in metronidazole-resistant Bacteroides fragilis isolates. Recombinant Giardia, Entamoeba, and Trichomonas nitroreductases used NADH rather than the NADPH used by Helicobacter, and two recombinant Entamoeba nitroreductases increased the metronidazole sensitivity of transformed Escherichia coli strains. Conversely, the recombinant nitroimidazole reductases (NIMs) of Entamoeba and Trichmonas conferred very strong metronidazole resistance to transformed bacteria. The Ehntr1 gene of the genome project HM-1:IMSS strain of Entamoeba histolytica had a nonsense mutation, and the same nonsense mutation was present in 3 of 22 clinical isolates of Entamoeba. While ntr and nim mRNAs were variably expressed by cultured Entamoeba and Trichomonas isolates, there was no relationship to metronidazole sensitivity. We conclude that microaerophilic protists have bacterium-like enzymes capable of activating metronidazole (nitroreductases) and inactivating metronidazole (NIMs). While Entamoeba and Trichomonas displayed some of the changes (nonsense mutations and gene overexpression) associated with metronidazole resistance in bacteria, these changes did not confer metronidazole resistance to the microaerophilic protists examined here.

  2. Biomimetic sensor based on molecularly imprinted polymer with nitroreductase-like activity for metronidazole detection.

    PubMed

    Gu, Yue; Yan, Xiaoyi; Li, Cong; Zheng, Bo; Li, Yaru; Liu, Weilu; Zhang, Zhiquan; Yang, Ming

    2016-03-15

    The utility of molecularly imprinted polymer (MIP) as electrochemical sensor often suffers from its limited catalytic efficiency. Here, we proposed an alternative approach by combining the concept of MIP with the use of mimetic enzyme. A metronidazole imprinted polymer with nitroreductase-like activity was successfully achieved via an electrochemical method, where melamine served two purposes: functional monomer of MIP and component of mimetic enzyme. During the imprinting process, the redox-active center, which is responsible for catalysis, was introduced into the imprinted cavities. Accordingly, the imprinted polymer, having both catalysis centers and recognition sites, exhibited enhanced electrocatalytic activity and selectivity. The sensing performances of this metronidazole imprinted biomimetic sensor were evaluated in detail. Results revealed that the response to metronidazole was linear in the concentration range of 0.5-1000 μM, and the detection limit was 0.12 μM (S/N=3). In addition, we applied the proposed sensor to detect metronidazole in an injection solution and the results implied its feasibility for practical application.

  3. Comparative characterisation of two nitroreductases from Giardia lamblia as potential activators of nitro compounds.

    PubMed

    Müller, Joachim; Rout, Samuel; Leitsch, David; Vaithilingam, Jathana; Hehl, Adrian; Müller, Norbert

    2015-08-01

    Giardia lamblia is a protozoan parasite that causes giardiasis, a diarrhoeal disease affecting humans and various animal species. Nitro drugs such as the nitroimidazole metronidazole and the nitrothiazolide nitazoxanide are used for treatment of giardiasis. Nitroreductases such as GlNR1 and GlNR2 may play a role in activation or inactivation of these drugs. The aim of this work is to characterise these two enyzmes using functional assays. For respective analyses recombinant analogues from GlNR1 and GlNR2 were produced in Escherichia coli. E. coli expressing GlNR1 and GlNR2 alone or together were grown in the presence of nitro compounds. Furthermore, pull-down assays were performed using HA-tagged GlNR1 and GlNR2 as baits. As expected, E. coli expressing GlNR1 were more susceptible to metronidazole under aerobic and semi-aerobic and to nitazoxanide under semi-aerobic growth conditions whereas E. coli expressing GlNR2 were susceptible to neither drug. Interestingly, expression of both nitroreductases gave the same results as expression of GlNR2 alone. In functional assays, both nitroreductases had their strongest activities on the quinone menadione (vitamin K3) and FAD, but reduction of nitro compounds including the nitro drugs metronidazole and nitazoxanide was clearly detected. Full reduction of 7-nitrocoumarin to 7-aminocoumarin was preferentially achieved with GlNR2. Pull-down assays revealed that GlNR1 and GlNR2 interacted in vivo forming a multienzyme complex. These findings suggest that both nitroreductases are multifunctional. Their main biological role may reside in the reduction of vitamin K analogues and FAD. Activation by GlNR1 or inactivation by GlNR2 of nitro drugs may be the consequence of a secondary enzymatic activity either yielding (GlNR1) or eliminating (GlNR2) toxic intermediates after reduction of these compounds.

  4. Trichomonas vaginalis Metronidazole Resistance Is Associated with Single Nucleotide Polymorphisms in the Nitroreductase Genes ntr4Tv and ntr6Tv

    PubMed Central

    Paulish-Miller, Teresa E.; Augostini, Peter; Schuyler, Jessica A.; Smith, William L.; Mordechai, Eli; Adelson, Martin E.; Gygax, Scott E.; Secor, William E.

    2014-01-01

    Metronidazole resistance in the sexually transmitted parasite Trichomonas vaginalis is a problematic public health issue. We have identified single nucleotide polymorphisms (SNPs) in two nitroreductase genes (ntr4Tv and ntr6Tv) associated with resistance. These SNPs were associated with one of two distinct T. vaginalis populations identified by multilocus sequence typing, yet one SNP (ntr6Tv A238T), which results in a premature stop codon, was associated with resistance independent of population structure and may be of diagnostic value. PMID:24550324

  5. Nitroreductase-triggered activation of a novel caged fluorescent probe obtained from methylene blue.

    PubMed

    Bae, Jungeun; McNamara, Louis E; Nael, Manal A; Mahdi, Fakhri; Doerksen, Robert J; Bidwell, Gene L; Hammer, Nathan I; Jo, Seongbong

    2015-08-18

    A near-infrared fluorescent probe based on methylene blue (p-NBMB) was developed for the detection of nitroreductase. Conjugating methylene blue with a p-nitrobenzyl moiety enables it to be activated by nitroreductase-catalyzed 1,6-elimination, resulting in the release of an active methylene blue fluorophore.

  6. Transcriptomics Indicates Active and Passive Metronidazole Resistance Mechanisms in Three Seminal Giardia Lines

    PubMed Central

    Ansell, Brendan R. E.; Baker, Louise; Emery, Samantha J.; McConville, Malcolm J.; Svärd, Staffan G.; Gasser, Robin B.; Jex, Aaron R.

    2017-01-01

    Giardia duodenalis is an intestinal parasite that causes 200–300 million episodes of diarrhoea annually. Metronidazole (Mtz) is a front-line anti-giardial, but treatment failure is common and clinical resistance has been demonstrated. Mtz is thought to be activated within the parasite by oxidoreductase enzymes, and to kill by causing oxidative damage. In G. duodenalis, Mtz resistance involves active and passive mechanisms. Relatively low activity of iron-sulfur binding proteins, namely pyruvate:ferredoxin oxidoreductase (PFOR), ferredoxins, and nitroreductase-1, enable resistant cells to passively avoid Mtz activation. Additionally, low expression of oxygen-detoxification enzymes can allow passive (non-enzymatic) Mtz detoxification via futile redox cycling. In contrast, active resistance mechanisms include complete enzymatic detoxification of the pro-drug by nitroreductase-2 and enhanced repair of oxidized biomolecules via thioredoxin-dependent antioxidant enzymes. Molecular resistance mechanisms may be largely founded on reversible transcriptional changes, as some resistant lines revert to drug sensitivity during drug-free culture in vitro, or passage through the life cycle. To comprehensively characterize these changes, we undertook strand-specific RNA sequencing of three laboratory-derived Mtz-resistant lines, 106-2ID10, 713-M3, and WB-M3, and compared transcription relative to their susceptible parents. Common up-regulated genes encoded variant-specific surface proteins (VSPs), a high cysteine membrane protein, calcium and zinc channels, a Mad-2 cell cycle regulator and a putative fatty acid α-oxidase. Down-regulated genes included nitroreductase-1, putative chromate and quinone reductases, and numerous genes that act proximal to PFOR. Transcriptional changes in 106-2ID10 diverged from those in 713-r and WB-r (r ≤ 0.2), which were more similar to each other (r = 0.47). In 106-2ID10, a nonsense mutation in nitroreductase-1 transcripts could enhance passive

  7. [Metronidazole].

    PubMed

    Martinez, V; Caumes, E

    2001-09-01

    Metronidazole was first introduced for the treatment of trichomoniasis. Now, its therapeutics use has subsequently been expanded to include protozoal and anaerobic infections. Oral administration is recommended: rosacea, perioral dermatitis, Helicobacter pylori, Trichomonas vaginalis and Giardia lamblia infections and bacterial vaginosis. Metronidazole given orally is absorbed almost completely. Metronidazole has limited plasma protein binding but can reach very favourable tissue distribution, including central nervous system and placenta. This drug is extensively metabolised by the liver to form 5 oxydative metabolites. The majority of this drug and metabolites are excreted in urine and feces. The half-life is 6 to 10 hours. The recommended dose is 500 mg three time per day and an adaptation is necessary in renal insufficiency. Metronidazole is well tolerated when administered in dosages of less than 2 g per day. Some adverse reactions appear to be related to the high dosages and treatment duration. Drug interactions with alcohol, warfarin and phenytoin have been reported. Mutagenesis and cancerogenesis is only described in mouse. Resistance, both clinical and microbiological, has been described only rarely.

  8. Metronidazole-triazole conjugates: Activity against Clostridium difficile and parasites

    PubMed Central

    Jarrad, Angie M.; Karoli, Tomislav; Debnath, Anjan; Tay, Chin Yen; Huang, Johnny X.; Kaeslin, Geraldine; Elliott, Alysha G.; Miyamoto, Yukiko; Ramu, Soumya; Kavanagh, Angela M.; Zuegg, Johannes; Eckmann, Lars; Blaskovich, Mark A.T.; Cooper, Matthew A.

    2015-01-01

    Metronidazole has been used clinically for over 50 years as an antiparasitic and broad-spectrum antibacterial agent effective against anaerobic bacteria. However resistance to metronidazole in parasites and bacteria has been reported, and improved second-generation metronidazole analogues are needed. The copper catalysed Huigsen azide-alkyne 1,3-dipolar cycloaddition offers a way to efficiently assemble new libraries of metronidazole analogues. Several new metronidazole-triazole conjugates (Mtz-triazoles) have been identified with excellent broad spectrum antimicrobial and antiparasitic activity targeting Clostridium difficile, Entamoeba histolytica and Giardia lamblia. Cross resistance to metronidazole was observed against stable metronidazole resistant C. difficile and G. lamblia strains. However for the most potent Mtz-triazoles, the activity remained in a therapeutically relevant window. PMID:26117821

  9. Metronidazole-triazole conjugates: activity against Clostridium difficile and parasites.

    PubMed

    Jarrad, Angie M; Karoli, Tomislav; Debnath, Anjan; Tay, Chin Yen; Huang, Johnny X; Kaeslin, Geraldine; Elliott, Alysha G; Miyamoto, Yukiko; Ramu, Soumya; Kavanagh, Angela M; Zuegg, Johannes; Eckmann, Lars; Blaskovich, Mark A T; Cooper, Matthew A

    2015-08-28

    Metronidazole has been used clinically for over 50 years as an antiparasitic and broad-spectrum antibacterial agent effective against anaerobic bacteria. However resistance to metronidazole in parasites and bacteria has been reported, and improved second-generation metronidazole analogues are needed. The copper catalysed Huigsen azide-alkyne 1,3-dipolar cycloaddition offers a way to efficiently assemble new libraries of metronidazole analogues. Several new metronidazole-triazole conjugates (Mtz-triazoles) have been identified with excellent broad spectrum antimicrobial and antiparasitic activity targeting Clostridium difficile, Entamoeba histolytica and Giardia lamblia. Cross resistance to metronidazole was observed against stable metronidazole resistant C. difficile and G. lamblia strains. However for the most potent Mtz-triazoles, the activity remained in a therapeutically relevant window.

  10. APPLICATION OF 6-NITROCOUMARIN AS A SUBSTRATE FOR THE FLUORESCENT DETECTION OF NITROREDUCTASE ACTIVITY IN Sporothrix schenckii

    PubMed Central

    Stopiglia, Cheila Denise Ottonelli; Carissimi, Mariana; Daboit, Tatiane Caroline; Stefani, Valter; Corbellini, Valeriano Antonio; Scroferneker, Maria Lúcia

    2013-01-01

    Introduction Sporothrix schenckii is a thermal dimorphic pathogenic fungus causing a subcutaneous mycosis, sporotrichosis. Nitrocoumarin represents a fluorogenic substrate class where the microbial nitroreductase activity produces several derivatives, already used in several other enzyme assays. The objective of this study was the analysis of 6-nitrocoumarin (6-NC) as a substrate to study the nitroreductase activity in Sporothrix schenckii. Methods Thirty-five samples of S. schenckii were cultivated for seven, 14 and 21 days at 35 °C in a microculture containing 6-nitrocoumarin or 6-aminocoumarin (6-AC) dissolved in dimethyl sulfoxide or dimethyl sulfoxide as a negative control, for posterior examination under an epifluorescence microscope. The organic layer of the seven, 14 and 21-day cultures was analyzed by means of direct illumination with 365 nm UV light and by means of elution on G silica gel plate with hexane:ethyl acetate 1:4 unveiled with UV light. Results All of the strains showed the presence of 6-AC (yellow fluorescence) and 6-hydroxylaminocoumarin (blue fluorescence) in thin layer chromatography, which explains the green fluorescence observed in the fungus structure. Conclusion The nitroreductase activity is widely distributed in the S. schenckii complex and 6-NC is a fluorogenic substrate of easy access and applicability for the nitroreductase activity detection. PMID:24037291

  11. Activation of Bicyclic Nitro-drugs by a Novel Nitroreductase (NTR2) in Leishmania

    PubMed Central

    Patterson, Stephen; Read, Kevin D.

    2016-01-01

    Drug discovery pipelines for the “neglected diseases” are now heavily populated with nitroheterocyclic compounds. Recently, the bicyclic nitro-compounds (R)-PA-824, DNDI-VL-2098 and delamanid have been identified as potential candidates for the treatment of visceral leishmaniasis. Using a combination of quantitative proteomics and whole genome sequencing of susceptible and drug-resistant parasites we identified a putative NAD(P)H oxidase as the activating nitroreductase (NTR2). Whole genome sequencing revealed that deletion of a single cytosine in the gene for NTR2 that is likely to result in the expression of a non-functional truncated protein. Susceptibility of leishmania was restored by reintroduction of the wild-type gene into the resistant line, which was accompanied by the ability to metabolise these compounds. Overexpression of NTR2 in wild-type parasites rendered cells hyper-sensitive to bicyclic nitro-compounds, but only marginally to the monocyclic nitro-drugs, nifurtimox and fexinidazole sulfone, known to be activated by a mitochondrial oxygen-insensitive nitroreductase (NTR1). Conversely, a double knockout NTR2 null cell line was completely resistant to bicyclic nitro-compounds and only marginally resistant to nifurtimox. Sensitivity was fully restored on expression of NTR2 in the null background. Thus, NTR2 is necessary and sufficient for activation of these bicyclic nitro-drugs. Recombinant NTR2 was capable of reducing bicyclic nitro-compounds in the same rank order as drug sensitivity in vitro. These findings may aid the future development of better, novel anti-leishmanial drugs. Moreover, the discovery of anti-leishmanial nitro-drugs with independent modes of activation and independent mechanisms of resistance alleviates many of the concerns over the continued development of these compound series. PMID:27812217

  12. Reduction of beta-glucuronidase and nitroreductase activity by yoghurt in a murine colon cancer model.

    PubMed

    de Moreno de LeBlanc, A; Perdigón, G

    2005-04-01

    Yoghurt feeding inhibits induced colon cancer in mice. Several studies showed the immunomodulatory effect of yoghurt which can explain this inhibition. It is possible that yoghurt bacteria can also affect gut flora enzymes related to colon carcinogenesis as reported for other probiotics in different animal tumours. The aim of this work was to evaluate the role of yoghurt starter bacteria and their cell-free fermentation products on the reduction of procarcinogen enzyme activities (beta-glucuronidase and nitroreductase). Mice injected with 1,2-dimethylhydrazine (DMH) and fed with yoghurt were used for this study. Mice given milk or yoghurt supernatant (cell free extract) were used to evaluate if the yoghurt antitumour effect is due to the starter bacteria or other components released during fermentation, that could inhibit these enzymes. We determined that yoghurt by itself maintained enzymes activities similar or lower than non-treatment control group, and the enzyme activity was also lower than milk or yoghurt supernatant groups. DMH increased the activity of the enzymes. Mice injected with DMH and fed cyclically with yoghurt presented lower enzymes activities than the tumour control group. Feeding yoghurt decreased procarcinogenic enzyme levels in the large intestine contents of mice bearing colon tumour. The results of this study provide another mechanism by which yoghurt starter bacteria interact with the large intestine of the mice and prevent colon cancer.

  13. Metronidazole activation and isolation of Clostridium acetobutylicum electron transport genes.

    PubMed Central

    Santangelo, J D; Jones, D T; Woods, D R

    1991-01-01

    An Escherichia coli F19 recA, nitrate reductase-deficient mutant was constructed by transposon mutagenesis and shown to be resistant to metronidazole. This mutant was a most suitable host for the isolation of Clostridium acetobutylicum genes on recombinant plasmids, which activated metronidazole and rendered the E. coli F19 strain sensitive to metronidazole. Twenty-five E. coli F19 clones containing different recombinant plasmids were isolated and classified into five groups on the basis of their sensitivity to metronidazole. The clones were tested for nitrate reductase, pyruvate-ferredoxin oxidoreductase, and hydrogenase activities. DNA hybridization and restriction endonuclease mapping revealed that four of the C. acetobutylicum insert DNA fragments on recombinant plasmids were linked in an 11.1-kb chromosomal fragment. DNA sequencing and amino acid homology studies indicated that this DNA fragment contained a flavodoxin gene which encoded a protein of 160 amino acids that activated metronidazole and made the E. coli F19 mutant very sensitive to metronidazole. The flavodoxin and hydrogenase genes which are involved in electron transfer systems were linked on the 11.1-kb DNA fragment from C. acetobutylicum. Images PMID:1991710

  14. Effects of metronidazole and its metabolites on histamine immunosuppression activity.

    PubMed

    Elizondo, G; Ostrosky-Wegman, P

    1996-01-01

    We have previously reported that metronidazole treatment increases human lymphocyte proliferation showing individual differences. This drug and its metabolites are imidazole compounds like histamine and cimetidine. The first is an endogenous amine that inhibits T-helper lymphocyte proliferation, and the second is a histamine antagonist. We presently report the in vitro effects of histamine, cimetidine, imidazole, metronidazole and its two principal metabolites (the acetic acid and hydroxy forms), on the mitogenic response to phytohemagglutinin (PHA) stimulation of human peripheral blood lymphocytes. Histamine decreased lymphocyte proliferation while (in order of potency) cimetidine, the hydroxy metabolite of metronidazole, imidazole and metronidazole, increased the mitogenic response to PHA in a dose-response fashion. The acetic acid metabolite lacked immunomodulatory effects. Competitive studies showed that cimetidine, metronidazole, and the hydroxy metabolite blocked the inhibitory effect of histamine on lymphocyte proliferation in a dose-related manner. This blockage was non-competitive, suggesting that the target of the imidazole compounds was not the active site of the H2 receptor.

  15. The aerobic activity of metronidazole against anaerobic bacteria.

    PubMed

    Dione, Niokhor; Khelaifia, Saber; Lagier, Jean-Christophe; Raoult, Didier

    2015-05-01

    Recently, the aerobic growth of strictly anaerobic bacteria was demonstrated using antioxidants. Metronidazole is frequently used to treat infections caused by anaerobic bacteria; however, to date its antibacterial activity was only tested in anaerobic conditions. Here we aerobically tested using antioxidants the in vitro activities of metronidazole, gentamicin, doxycycline and imipenem against 10 common anaerobic and aerobic bacteria. In vitro susceptibility testing was performed by the disk diffusion method, and minimum inhibitory concentrations (MICs) were determined by Etest. Aerobic culture of the bacteria was performed at 37°C using Schaedler agar medium supplemented with 1mg/mL ascorbic acid and 0.1mg/mL glutathione; the pH was adjusted to 7.2 by 10M KOH. Growth of anaerobic bacteria cultured aerobically using antioxidants was inhibited by metronidazole after 72h of incubation at 37°C, with a mean inhibition diameter of 37.76mm and an MIC of 1μg/mL; however, strains remained non-sensitive to gentamicin. No growth inhibition of aerobic bacteria was observed after 24h of incubation at 37°C with metronidazole; however, inhibition was observed with doxycycline and imipenem used as controls. These results indicate that bacterial sensitivity to metronidazole is not related to the oxygen tension but is a result of the sensitivity of the micro-organism. In future, both culture and antibiotic susceptibility testing of strictly anaerobic bacteria will be performed in an aerobic atmosphere using antioxidants in clinical microbiology laboratories.

  16. Microparticles containing propolis and metronidazole: in vitro characterization, release study and antimicrobial activity against periodontal pathogens.

    PubMed

    de Souza Ferreira, Sabrina Barbosa; de Assis Dias, Bruno Rafael; Obregón, Clarissa Silva; Gomes, Carla Carolina; de Araújo Pereira, Raphaela Regina; Ribeiro Godoy, Janine Silva; Estivalet Svidzinski, Terezinha Inez; Bruschi, Marcos Luciano

    2014-03-01

    Ethylcellulose microparticles containing metronidazole and propolis extractive solution were prepared and evaluated in vitro against periodontal pathogens. Scanning electron microscopy, particle size analysis, drug entrapment efficiency and drug release of microparticles were determined. The antimicrobial activity of microparticles was evaluated against microorganisms of periodontal importance (Enterococcus faecalis, Streptococcus pyogenes, Streptococcus mutans, Staphylococcus aureus, Klebsiella pneumoniae and Escherichia coli). It was obtained particles with regular morphology, mean diameter of 1.23 µm, and entrapment efficiency for propolis and metronidazole were 91.41% and 22.23%, respectively. In vitro release studies of propolis and metronidazole from microparticles showed prolonged drug release and controlled by Fickian diffusion. Both propolis and metronidazole displayed activity against the tested strains. Moreover, the results showed that the strains of E. faecalis, S. pyogenes and S. mutans were more susceptible to the propolis and E. faecalis to the metronidazole. It was also observed that the amount of metronidazole to inhibit the microorganism strains in the physical mixture with propolis was smaller than in the metronidazole alone, suggesting potentiation effect between propolis and metronidazole. These microparticles would be useful for developing intermediary or eventual dosage form to be administered into the periodontal pocket more easily and safely.

  17. Cytogenetic study of metronidazole and three metronidazole analogues in cultured human lymphocytes with and without metabolic activation.

    PubMed

    Gómez-Arroyo, Sandra; Melchor-Castro, Sara; Villalobos-Pietrini, Rafael; Camargo, Estela Meléndez; Salgado-Zamora, Héctor; Campos Aldrete, Maria Elena

    2004-06-01

    Metronidazole (MTZ) and other nitroimidazole derivatives have been extensively used to treat infections caused by protozoa and anaerobic bacteria. However, the need for new derivatives with similar therapeutic activity but lower toxicity to human beings prevails. On this purpose, three metronidazole analogues were synthesized, namely: 1-(p-methylphenacyl)-2-methyl-4-nitro imidazole (CPMe), 1-(p-methoxyphenacyl)-2-methyl-4-nitroimidazole (CPMeO), and 1-(p-fluorphenacyl)-2-methyl-4-nitroimidazole (CPF), which at low concentrations (0.5-2 microg/ml) showed a higher activity against Entamoeba histolytica than MTZ (3-6 microg/ml). The aim of this work was to investigate the cytogenetic effect of the three MTZ analogues on human lymphocyte cultures with and without metabolic activation in vitro, using the sister chromatid exchange test (SCE), comparatively with MTZ. The effect of the compounds on the cell proliferation kinetics (CPK) measured by the replication index (RI) and the cytotoxic effect in the mitotic index (MI) was evaluated as well. The SCE frequencies with and without S9 metabolic activation in treated and control lymphocytes showed no significant statistical differences. However when metabolic activation was involved a significant increase in the amount of third division metaphases provoked the CPK increased significantly with all the tested compounds. The RI showed similar behaviour, except for compound CPF.

  18. Application of Salmonella strains with altered nitroreductase and O-acetyltransferase activities to the evaluation of the mutagenicity of airborne particles.

    PubMed

    Adamiak, W; Jadczyk, P; Kucharczyk, J

    1999-01-01

    The Ames test was applied to evaluation of the mutagenicity of month's samples of airborne particles from the center of Wrocław (SW Poland) collected in August and December 1997. The strains used for the study were TA 98, TA 100 and their derivatives: TA 98 NR, YG 1021, YG 1024, YG 1026, YG 1029, YG 1041, YG 1042. Both studied samples were mutagenic for almost all tested strains, with the exception of the August sample which did not influence the strain TA 100 without the metabolic activation with the S9 fraction. The December sample exhibited higher genotoxic activity than the August sample. Mutagenicity ratios of the strains with reduced nitroreductase and O-acetyltransferase activities were higher, and of the strain without the nitroreductase--lower than those of the parent strains. This indicates that nitro and amino derivatives of PAHs are responsible for the significant proportion of total mutagenicity of the studied samples of particulates. Metabolic activation with the S9 fraction caused the increase of the mutagenic activity of the samples, which indicates the presence of promutagens. The GC-MS analysis revealed the presence of known indirect mutagens from the PAHs group.

  19. 2-(Nitroaryl)benzothiazole and benzoxazole derivatives as fluorogenic substrates for the detection of nitroreductase activity in clinically important microorganisms.

    PubMed

    Cellier, Marie; Gignoux, Amandine; James, Arthur L; Orenga, Sylvain; Perry, John D; Robinson, Shaun N; Stanforth, Stephen P; Turnbull, Graeme

    2015-12-15

    A series of carboxy-substituted 2-(nitroaryl)benzothiazole derivatives and carboxy-substituted 2-(nitroaryl)benzoxazole derivatives were prepared and evaluated as potential nitroreductase substrates for the purpose of detecting clinically important microorganisms. Several of the substrates produced highly fluorescent colonies with the majority of a panel of 10 Gram-negative bacteria and also with two of a panel of 8 Gram-positive bacteria.

  20. Evaluation of Nitrofurantoin Combination Therapy of Metronidazole-Sensitive and -Resistant Helicobacter pylori Infections in Mice

    PubMed Central

    Jenks, Peter J.; Ferrero, Richard L.; Tankovic, Jacques; Thiberge, Jean-Michel; Labigne, Agnès

    2000-01-01

    The main objectives of this study were to determine whether the nitroreductase enzyme encoded by the rdxA gene of Helicobacter pylori was responsible for reductive activation of nitrofurantoin and whether a triple-therapy regimen with nitrofurantoin was able to eradicate metronidazole-sensitive and -resistant H. pylori infections from mice. The susceptibilities to nitrofurantoin of parent and isogenic rdxA mutant strains (three pairs), as well as a series of matched metronidazole-sensitive and -resistant strains isolated from mice (30) and patients (20), were assessed by agar dilution determination of the MIC. Groups of mice colonized with the metronidazole-sensitive H. pylori SS1 strain or a metronidazole-resistant rdxA SS1 mutant were treated with either metronidazole or nitrofurantoin as part of a triple-therapy regimen. One month after the completion of treatment the mice were sacrificed and their stomachs were cultured for H. pylori. The nitrofurantoin MICs for all strains tested were between 0.5 and 4.0 μg/ml. There was no significant difference between the susceptibility to nitrofurantoin of the parental strains and those of respective rdxA mutants or between those of matched metronidazole-sensitive and -resistant H. pylori isolates. The regimen with metronidazole eradicated infection from all eight SS1-infected mice and from one of eight mice inoculated with the rdxA mutant (P ≤ 0.001). The regimen with nitrofurantoin failed to eradicate infection from any of the six SS1-infected mice (P ≤ 0.001) and cleared infection from one of seven mice inoculated with the rdxA mutant. These results demonstrate that, despite the good in vitro activity of nitrofurantoin against H. pylori and the lack of cross-resistance between metronidazole and nitrofurantoin, eradication regimens involving nitrofurantoin are unable to eradicate either metronidazole-sensitive or -resistant H. pylori infections from mice. PMID:10991835

  1. A comparative study of metronidazole and sulfasalazine for active Crohn's disease: the cooperative Crohn's disease study in Sweden. II. Result.

    PubMed

    Ursing, B; Alm, T; Bárány, F; Bergelin, I; Ganrot-Norlin, K; Hoevels, J; Huitfeldt, B; Järnerot, G; Krause, U; Krook, A; Lindström, B; Nordle, O; Rosén, A

    1982-09-01

    Seventy-eight patients with active Crohn's disease participated in a randomized, double-blind, cross-over trial. The study comprised two 4-mo period. The purpose was to test the efficacy of metronidazole in comparison with that of sulfasalazine. As the main evaluation criteria the Crohn's Disease Activity Index and plasma levels of orosomucoid were chosen. In the first period no difference in efficacy as measured by Crohn's Disease Activity Index was found between the treatment groups. The reduction of the plasma orosomucoid level was significantly more pronounced in the metronidazole group. The hemoglobin concentration increased more in this group than in the sulfasalazine group, possibly due to a toxic effect of sulfasalazine. The erythrocyte sedimentation rate decreased similarly with both drugs. In 15 patients who had active disease throughout the first period, Crohn's Disease Activity Index decreased significantly in the second period for those who switched to metronidazole, but not for those who switched to sulfasalazine. After crossover, no apparent further change in Crohn's Disease Activity Index occurred in either of the treatment groups among patients who had responded favorably in the first period. The plasma concentration of orosomucoid increased significantly among the patients in the sulfasalazine group but not in the metronidazole group. It is therefore concluded that metronidazole is slightly more effective than sulfasalazine in the treatment of crohn's disease. It is worthwhile switching the drug regimen from sulfasalazine, when it fails, to metronidazole, but not from metronidazole to sulfasalazine.

  2. Synthesis and evaluation of sulfate conjugated metronidazole as a colon-specific prodrug of metronidazole.

    PubMed

    Kim, Hyunjeong; Lee, Yonghyun; Yoo, Hansun; Kim, Jihye; Kong, Hyesik; Yoon, Jeong-Hyun; Jung, Yunjin; Kim, Young Mi

    2012-04-01

    For an effort to improve therapeutic property of metronidazole (MTZ) which is a drug of choice for protozoal infections such as luminal amoebiasis, sulfate conjugated metronidazole (MTZS) was prepared and evaluated as a colon-specific prodrug of MTZ. The apparent partition coefficient of MTZ was greatly reduced by the sulfate conjugation. While (bio)chemically stable in the contents of the upper intestine, MTZS was rapidly cleaved to liberate MTZ on incubation with the cecal contents of rats. MTZ liberated from MTZS metabolized quickly at least partly by a microbial nitroreductase, suggesting the relevance of the metabolism to bioactivation of MTZ for antimicrobial action. Consistent with the hypothesis, MTZS elicited antibacterial activity in the cecal contents, which was as potent as free MTZ. The systemic absorption of MTZS was very low after oral administration of MTZS. In parallel with this, whereas MTZ disappeared mostly during the transit of the proximal small intestine, a substantial amount of MTZS remained in the small intestine, moving down to the large intestine where it metabolized rapidly. In addition to the efficient colonic delivery of MTZS, MTZS markedly reduced the systemic absorption of MTZ. Taken together, MTZS may be a potential colon-specific prodrug of MTZ which possesses improved therapeutic and toxicological properties.

  3. Synthesis and QSAR study of novel anti-inflammatory active mesalazine-metronidazole conjugates.

    PubMed

    Naumov, Roman N; Panda, Siva S; Girgis, Adel S; George, Riham F; Farhat, Michel; Katritzky, Alan R

    2015-06-01

    Novel, mesalazine, metronidazole conjugates 6a-e with amino acid linkers were synthesized utilizing benzotriazole chemistry. Biological data acquired for all the novel bis-conjugates showed (a) some bis-conjugates exhibit comparable anti-inflammatory activity with parent drugs and (b) the potent bis-conjugates show no visible stomach lesions. 3D-pharmacophore and 2D-QSAR modeling support the observed bio-properties.

  4. Metronidazole Oral

    MedlinePlus

    Metronidazole eliminates bacteria and other microorganisms that cause infections of the reproductive system, gastrointestinal tract, skin, vagina, and other areas of the body. Antibiotics will not work ...

  5. Highly sensitive umu test system for the detection of mutagenic nitroarenes in Salmonella typhimurium NM3009 having high O-acetyltransferase and nitroreductase activities

    SciTech Connect

    Oda, Yoshimitsu; Yamazaki, Hiroshi; Watanabe, Masahiko; Nohmi, Takehiko; Shimada, Tsutomu )

    1993-01-01

    A highly sensitive umu test system for the detection of genotoxic activities of a variety of mutagenic nitroarenes has been developed using a new tester strain, Salmonella typhimurium NM3009 having high O-acetyltransferase (O-AT) and nitroreductase (NR) activities. The NM3009 was constructed by subcloning both the O-AT and NR genes into plasmid vector pACYC184, and the resulting plasmid was introduced into the parent tester strain S. typhimurium TA1535/pSK1002 harboring an umuC[prime]-[prime]lacZ fusion gene. The induction of umuC gene expression could be monitored by measuring the cellular [beta]-galactosidase activity produced by fusion gene. The purpose of the study was to evaluate whether the newly developed strain NM3009 is highly sensitive toward nitroarene compounds. The sensitivity of the strain NM3009 was compared with those of the parent TA1535/pSK1002 strain, the NR-overexpressing strain NM1011, the NR-deficient strain NM1000, the O-AT-overexpressing strain NM2009, and the O-AT-defective strain NM2000. The newly developed NM3009 strain had about 13-fold and 3-fold higher activities for N-AT and NR, respectively, than the original S. typhimurium TA1535/pSK1002 strain. Among six strains tested, NM3009 showed the highest sensitivity toward such chemicals as 1-nitronaphthalene, 2-nitrofluorene, 3,7-dinitro-fluoranthene, 3-nitrofluoranthene, 5-nitroacenaphthene, 2-nitronaphthalene, 1-nitropyrene, 1,6-dinitropyrene, 3,9-dinitrofluoranthene, 4,4[prime]-dinitrobiphenyl, 1,8-dinitropyrene, m-dinitrobenzene, 2,4-dinitrotoluene, and 1,3-dinitropyrene. The authors have also found that the order of sensitivities to induce umuC gene expression toward a variety of nitroarenes was NM3009 > NM2009 > NM1011 > TA1535/pSK1002 > NM2000 > NM1000. 40 refs., 3 figs., 3 tabs.

  6. Metronidazole Topical

    MedlinePlus

    Noritate® Cream ... Metronidazole comes as a cream, lotion, or gel to be applied to your skin and as a gel to be used in the vagina. Metronidazole ... applying the medication. Apply a thin layer of cream, lotion, or gel and rub it gently into ...

  7. Pharmacokinetics and serum bactericidal activities of quinolones in combination with clindamycin, metronidazole, and ornidazole.

    PubMed Central

    Boeckh, M; Lode, H; Deppermann, K M; Grineisen, S; Shokry, F; Held, R; Wernicke, K; Koeppe, P; Wagner, J; Krasemann, C

    1990-01-01

    To enhance the antimicrobial spectrum of the quinolones against anaerobic organisms and gram-positive bacteria, we investigated in two studies the parenteral combinations of ciprofloxacin (200 mg) and ofloxacin (200 mg) with metronidazole (500 mg) or clindamycin (600 mg) and the oral combinations of enoxacin (400 mg) and fleroxacin (400 mg) with metronidazole (400 mg), clindamycin (300 mg), or ornidazole (500 mg) (only with fleroxacin). The pharmacokinetics and serum bactericidal activities (SBAs) against 5 aerobic and 2 anaerobic species (total, 58 strains) were determined in two groups of 10 healthy volunteers by using a randomized crossover study design. The additions of metronidazole, clindamycin, and ornidazole did not affect the pharmacokinetics of the quinolones. The combination of clindamycin with ciprofloxacin, ofloxacin, and, to a lesser extent, fleroxacin resulted in an increase of the SBA against gram-positive strains (mean peak titers): Staphylococcus aureus, ciprofloxacin alone, 1:5.5; ciprofloxacin-clindamycin, 1:19.9; ofloxacin alone, 1:3.6; ofloxacin-clindamycin, 1:17.5; fleroxacin alone, 1:4.3; fleroxacin-clindamycin, 1:8.1; Streptococcus pneumoniae (fleroxacin and enoxacin were not tested), ciprofloxacin alone, 1:2.0; ciprofloxacin-clindamycin, 1:53; ofloxacin alone, 1:2.6; and ofloxacin-clindamycin, 1:49.2. The high SBA of quinolones against gram-negative bacteria was not affected by the combinations; however, relatively low activities against Pseudomonas aeruginosa were detected. In general, against anaerobic bacteria, low bactericidal activities were determined in both studies (mean peak titers ranged from 1:2.1 to 1:3.1; mean trough titers range from 1:2.0 to 1:2.9). In clinical settings with severe mixed infections, a parenteral therapy consisting of modern quinolones together with clindamycin or imidazole derivatives seems to be active and offers no obvious interactions. PMID:2088195

  8. Genotoxic effects of metronidazole.

    PubMed

    Elizondo, G; Gonsebatt, M E; Salazar, A M; Lares, I; Santiago, P; Herrera, J; Hong, E; Ostrosky-Wegman, P

    1996-09-13

    Metronidazole (MTZ) is an effective agent used in the treatment of parasitic infections. Its genotoxic effects have been shown in a variety of prokaryotic systems; however, negative results have been reported in human in vivo studies. Due to its wide spread use, a study was performed to evaluate the chromosomal aberration frequencies in peripheral blood lymphocyte cultures from 10 individuals, before and after metronidazole treatment. A significant increase in the percentage of cells with chromatid and isochromatid breaks was observed after metronidazole treatment (1500 mg per day for 10 days). The percentages of cells with aberrations did not correlate with the levels of MTZ found in plasma. Individual variability was observed with respect to both the induction of aberrations and the concentration of MTZ in plasma. They could represent differences at the metabolic level, since metronidazole is known to be biotransformed by a polymorphic P450 cytochrome, and its metabolites have shown mutagenic activity.

  9. Combined antitumor activity of the nitroreductase/CB1954 suicide gene system and γ-rays in HeLa cells in vitro

    PubMed Central

    Teng, Geling; Ju, Yuanrong; Yang, Yepeng; Hua, Hu; Chi, Jingyu; Mu, Xiuan

    2016-01-01

    Escherichia coli nitroreductase (NTR) may convert the prodrug CB1954 (5-(aziridin-1-yl)-2,4-dinitrobenzamide) into a bifunctional alkylating agent, which may lead to DNA crosslinks and the apoptosis of cancer cells. NTR/CB1954 has been demonstrated to be an effective gene therapy in cancer cells. The present study examined whether the NTR/CB1954 suicide gene system had cytotoxic effects on HeLa cells and may improve the radiosensitivity of HeLa cells to γ-rays. It was observed that the NTR/CB1954 suicide gene system exerted marked cytotoxic effects on HeLa cells. The combined therapeutic effects of NTR/CB1954 and γ-rays on HeLa cells demonstrated a synergistic effect. CB1954 at concentrations of 12.5 and 25 µmol/l increased the sensitization enhancement ratio of HeLa cells to 1.54 and 1.66, respectively. Therefore, when compared with monotherapy, the combined therapy of NTR/CB1954 and γ-rays may increase the apoptotic rate and enhance the radiosensitivity of HeLa cells. The combined therapy of γ-ray radiation and the NTR/CB1954 suicide gene system may be a novel and potent therapeutic method for the treatment of cervical carcinoma. PMID:27840931

  10. Combined antitumor activity of the nitroreductase/CB1954 suicide gene system and γ-rays in HeLa cells in vitro.

    PubMed

    Teng, Geling; Ju, Yuanrong; Yang, Yepeng; Hua, Hu; Chi, Jingyu; Mu, Xiuan

    2016-12-01

    Escherichia coli nitroreductase (NTR) may convert the prodrug CB1954 (5-(aziridin-1-yl)-2,4-dinitrobenzamide) into a bifunctional alkylating agent, which may lead to DNA crosslinks and the apoptosis of cancer cells. NTR/CB1954 has been demonstrated to be an effective gene therapy in cancer cells. The present study examined whether the NTR/CB1954 suicide gene system had cytotoxic effects on HeLa cells and may improve the radiosensitivity of HeLa cells to γ‑rays. It was observed that the NTR/CB1954 suicide gene system exerted marked cytotoxic effects on HeLa cells. The combined therapeutic effects of NTR/CB1954 and γ‑rays on HeLa cells demonstrated a synergistic effect. CB1954 at concentrations of 12.5 and 25 µmol/l increased the sensitization enhancement ratio of HeLa cells to 1.54 and 1.66, respectively. Therefore, when compared with monotherapy, the combined therapy of NTR/CB1954 and γ‑rays may increase the apoptotic rate and enhance the radiosensitivity of HeLa cells. The combined therapy of γ‑ray radiation and the NTR/CB1954 suicide gene system may be a novel and potent therapeutic method for the treatment of cervical carcinoma.

  11. Megazol and its bioisostere 4H-1,2,4-triazole: comparing the trypanocidal, cytotoxic and genotoxic activities and their in vitro and in silico interactions with the Trypanosoma brucei nitroreductase enzyme

    PubMed Central

    de Carvalho, Alcione Silva; Salomão, Kelly; de Castro, Solange Lisboa; Conde, Taline Ramos; Zamith, Helena Pereira da Silva; Caffarena, Ernesto Raúl; Hall, Belinda Suzette; Wilkinson, Shane Robert; Boechat, Núbia

    2014-01-01

    Megazol (7) is a 5-nitroimidazole that is highly active against Trypanosoma cruzi and Trypanosoma brucei, as well as drug-resistant forms of trypanosomiasis. Compound 7 is not used clinically due to its mutagenic and genotoxic properties, but has been largely used as a lead compound. Here, we compared the activity of 7 with its 4H-1,2,4-triazole bioisostere (8) in bloodstream forms of T. brucei and T. cruzi and evaluated their activation by T. brucei type I nitroreductase (TbNTR) enzyme. We also analysed the cytotoxic and genotoxic effects of these compounds in whole human blood using Comet and fluorescein diacetate/ethidium bromide assays. Although the only difference between 7 and 8 is the substitution of sulphur (in the thiadiazole in 7) for nitrogen (in the triazole in 8), the results indicated that 8 had poorer antiparasitic activity than 7 and was not genotoxic, whereas 7 presented this effect. The determination of Vmax indicated that although 8 was metabolised more rapidly than 7, it bounds to the TbNTR with better affinity, resulting in equivalent kcat/KM values. Docking assays of 7 and 8 performed within the active site of a homology model of the TbNTR indicating that 8 had greater affinity than 7. PMID:24676659

  12. Metronidazole. A therapeutic review and update.

    PubMed

    Freeman, C D; Klutman, N E; Lamp, K C

    1997-11-01

    The nitroimidazole antibiotic metronidazole has a limited spectrum of activity that encompasses various protozoans and most Gram-negative and Gram-positive anaerobic bacteria. Metronidazole has activity against protozoans like Entamoeba histolytica, Giardia lamblia and Trichomonas vaginalis, for which the drug was first approved as an effective treatment. Anaerobic bacteria which are typically sensitive are primarily Gram-negative anaerobes belonging to the Bacteroides and Fusobacterium spp. Gram-positive anaerobes such as peptostreptococci and Clostridia spp. are likely to test sensitive to metronidazole, but resistant isolates are probably encountered with greater frequency than with the Gram-negative anaerobes. Gardnerella vaginalis is a pleomorphic Gram-variable bacterial bacillus that is also susceptible to metronidazole. Helicobacter pylori has been strongly associated with gastritis and duodenal ulcers. Classic regimens for eradicating this pathogen have included metronidazole, usually with acid suppression medication plus bismuth and amoxicillin. The activity of metronidazole against anaerobic bowel flora has been used for prophylaxis and treatment of patients with Crohn's disease who might develop an infectious complication. Treatment of Clostridium difficile-induced pseudomembraneous colitis has usually been with oral metronidazole or vancomycin, but the lower cost and similar efficacy of metronidazole, coupled with the increased concern about imprudent use of vancomycin leading to increased resistance in enterococci, have made metronidazole the preferred agent here. Metronidazole has played an important role in anaerobic-related infections. Advantages to using metronidazole are the percentage of sensitive Gram-negative anaerobes, its availability as oral and intravenous dosage forms, its rapid bacterial killing, its good tissue penetration, its considerably lower chance of inducing C. difficile colitis, and expense. Metronidazole has notable

  13. Overall adsorption rate of metronidazole, dimetridazole and diatrizoate on activated carbons prepared from coffee residues and almond shells.

    PubMed

    Flores-Cano, J V; Sánchez-Polo, M; Messoud, J; Velo-Gala, I; Ocampo-Pérez, R; Rivera-Utrilla, J

    2016-03-15

    This study analyzed the overall adsorption rate of metronidazole, dimetridazole, and diatrizoate on activated carbons prepared from coffee residues and almond shells. It was also elucidated whether the overall adsorption rate was controlled by reaction on the adsorbent surface or by intraparticle diffusion. Experimental data of the pollutant concentration decay curves as a function of contact time were interpreted by kinetics (first- and second-order) and diffusion models, considering external mass transfer, surface and/or pore volume diffusion, and adsorption on an active site. The experimental data were better interpreted by a first-order than second-order kinetic model, and the first-order adsorption rate constant varied linearly with respect to the surface area and total pore volume of the adsorbents. According to the diffusion model, the overall adsorption rate is governed by intraparticle diffusion, and surface diffusion is the main mechanism controlling the intraparticle diffusion, representing >90% of total intraparticle diffusion.

  14. Quinone- and nitroreductase reactions of Thermotoga maritima peroxiredoxin-nitroreductase hybrid enzyme.

    PubMed

    Anusevičius, Žilvinas; Misevičienė, Lina; Šarlauskas, Jonas; Rouhier, Nicolas; Jacquot, Jean-Pierre; Čėnas, Narimantas

    2012-12-01

    Thermotoga maritima peroxiredoxin-nitroreductase hybrid enzyme (Prx-NR) consists of a FMN-containing nitroreductase (NR) domain fused to a peroxiredoxin (Prx) domain. These domains seem to function independently as no electron transfer occurs between them. The reduction of quinones and nitroaromatics by NR proceeded in a two-electron manner, and follows a 'ping-pong' scheme with sometimes pronounced inhibition by quinone substrate. The comparison of steady- and presteady-state kinetic data shows that in most cases, the oxidative half-reaction may be rate-limiting in the catalytic cycle of NR. The enzyme was inhibited by dicumarol, a classical inhibitor of oxygen-insensitive nitroreductases. The reduction of quinones and nitroaromatic compounds by Prx-NR was characterized by the linear dependence of their reactivity (logk(cat)/K(m)) on their single-electron reduction potentials E(7)(1), while the reactivity of quinones markedly exceeded the one with nitroaromatics. It shows that NR lacks the specificity for the particular structure of these oxidants, except their single-electron accepting potency and the rate of electron self-exchange. It points to the possibility of a single-electron transfer step in a net two-electron reduction of quinones and nitroaromatics by T. maritima Prx-NR, and to a significant diversity of the structures of flavoenzymes which may perform the two-electron reduction of quinones and nitroaromatics.

  15. Identification of novel nitroreductases from Bacillus cereus and their interaction with the CB1954 prodrug.

    PubMed

    Gwenin, Vanessa V; Poornima, Paramasivan; Halliwell, Jennifer; Ball, Patrick; Robinson, George; Gwenin, Chris D

    2015-12-01

    Directed enzyme prodrug therapy is a form of cancer chemotherapy in which bacterial prodrug-activating enzymes, or their encoding genes, are directed to the tumour before administration of a prodrug. The prodrug can then be activated into a toxic drug at the tumour site, reducing off-target effects. The bacterial nitroreductases are a class of enzymes used in this therapeutic approach and although very promising, the low turnover rate of prodrug by the most studied nitroreductase enzyme, NfnB from Escherichia coli (NfnB_Ec), is a major limit to this technology. There is a continual search for enzymes with greater efficiency, and as part of the search for more efficient bacterial nitroreductase enzymes, two novel enzymes from Bacillus cereus (strain ATCC 14579) have been identified and shown to reduce the CB1954 (5-(aziridin-1-yl)-2,4-dinitrobenzamide) prodrug to its respective 2'-and 4'-hydroxylamine products. Both enzymes shared features characteristic of the nitro-FMN-reductase superfamily including non-covalently associated FMN, requirement for the NAD(P)H cofactor, homodimeric, could be inhibited by Dicoumarol (3,3'-methylenebis(4-hydroxy-2H-chromen-2-one)), and displayed ping pong bi bi kinetics. Based on the biochemical characteristics and nucleotide alignment with other nitroreductase enzymes, one enzyme was named YdgI_Bc and the other YfkO_Bc. Both B. cereus enzymes had greater turnover for the CB1954 prodrug compared with NfnB_Ec, and in the presence of added NADPH cofactor, YfkO_Bc had superior cell killing ability, and produced mainly the 4'-hydroxylamine product at low prodrug concentration. The YfkO_Bc was identified as a promising candidate for future enzyme prodrug therapy.

  16. Purification and characterization of NAD(P)H-dependent nitroreductase I from Klebsiella sp. C1 and enzymatic transformation of 2,4,6-trinitrotoluene.

    PubMed

    Kim, Hyoun-Young; Song, Hong-Gyu

    2005-10-01

    Three NAD(P)H-dependent nitroreductases that can transform 2,4,6-trinitrotoluene (TNT) by two reduction pathways were detected in Klebsiella sp. C1. Among these enzymes, the protein with the highest reduction activity of TNT (nitroreductase I) was purified to homogeneity using ion-exchange, hydrophobic interaction, and size exclusion chromatographies. Nitroreductase I has a molecular mass of 27 kDa as determined by SDS-PAGE, and exhibits a broad pH optimum between 5.5 and 6.5, with a temperature optimum of 30-40 degrees C. Flavin mononucleotide is most likely the natural flavin cofactor of this enzyme. The N-terminal amino acid sequence of this enzyme does not show a high degree of sequence similarity with nitroreductases from other enteric bacteria. This enzyme catalyzed the two-electron reduction of several nitroaromatic compounds with very high specific activities of NADPH oxidation. In the enzymatic transformation of TNT, 2-amino-4,6-dinitrotoluene and 2,2',6,6'-tetranitro-4,4'-azoxytoluene were detected as transformation products. Although this bacterium utilizes the direct ring reduction and subsequent denitration pathway together with a nitro group reduction pathway, metabolites in direct ring reduction of TNT could not easily be detected. Unlike other nitroreductases, nitroreductase I was able to transform hydroxylaminodinitrotoluenes (HADNT) into aminodinitrotoluenes (ADNT), and could reduce ortho isomers (2-HADNT and 2-ADNT) more easily than their para isomers (4-HADNT and 4-ADNT). Only the nitro group in the ortho position of 2,4-DNT was reduced to produce 2-hydroxylamino-4-nitrotoluene by nitroreductase I; the nitro group in the para position was not reduced.

  17. Synthesis, characterization and antimicrobial activity of water-soluble silver(i) complexes of metronidazole drug and selected counter-ions.

    PubMed

    Kalinowska-Lis, Urszula; Felczak, Aleksandra; Chęcińska, Lilianna; Zawadzka, Katarzyna; Patyna, Emilia; Lisowska, Katarzyna; Ochocki, Justyn

    2015-05-07

    A series of water-soluble silver(i) complexes of the type [Ag(MTZ)2X] [MTZ = 1-(2-hydroxyethyl)-2-methyl-5-nitro-1H-imidazole (metronidazole drug); X = NO3(-), ClO4(-), CF3COO(-), BF4(-) and CH3SO3(-)] was synthesised by the reactions of various Ag(i) salts with metronidazole (MTZ). All the complexes were characterized by ESI-MS spectrometry, solution NMR ((1)H and (13)C) and IR spectroscopy, and elemental analysis. Further evidence for the formation and molecular structure of all the complexes was provided by X-ray single-crystal crystallography. The different counter ions affect the crystal packing of the complexes and thus have an impact on the final geometries. The antimicrobial activities of the complexes against two Gram-positive strains: Staphylococcus aureus ATCC 6538, Staphylococcus epidermidis ATCC 12228, three Gram-negative strains: Pseudomonas aeruginosa ATCC 15442, Escherichia coli ATCC 25922, Proteus hauseri ATCC 13315 and yeast Candida albicans ATCC 10231 were evaluated and compared with antibacterial and antifungal properties of appropriate silver salts, metronidazole and silver sulfadiazine drugs. The newly synthesized compounds exhibited significant antibacterial activity against Gram-positive bacteria, better than the referenced silver sulfadiazine. The best active silver(i)-metronidazole complex contains a methanesulphonate counter-ion. Moreover, the complex inhibited the growth of yeast Candida albicans at a concentration 3-fold lower than that required for silver sulfadiazine. In addition, the complexes containing a tetrafluoroborate and a perchlorate as counter-ions were characterized as effective antibacterial agents against the tested Gram-negative bacteria.

  18. Metronidazole (Flagyl) and Pregnancy

    MedlinePlus

    ... sheets/ paternal- exposures- pregnancy/ . Selected References: Beard CM, et al. 1988. Cancer after expsoure to metronidazole. Mayo Clinic Proceedings 63(2):147-153. Beard CM, et al. 1979. Lack of evidence for cancer due ...

  19. Metronidazole and 5-aminosalicylic acid enhance the contractile activity of histaminergic agonists on the guinea-pig isolated ileum

    SciTech Connect

    Winbery, S.L.; Barker, L.A.

    1986-03-01

    The effects of metronidazole and 5-aminosalicylic acid (5-ASA) on histamine receptor-effector systems in the small intestine and right atrium of the guinea pig were studied. In an apparently all-or-none manner, both caused a sinistral shift in dose-response curves for the phasic component of the contractile response to histamine at H1 receptors on the ileum. In the presence of either, the EC50 value for histamine was reduced from 0.07 to about 0.03 microM. Similarly, in an apparently all-or-none fashion, both produced an elevation in the dose-response curve for the actions of dimaprit at H2-receptors in the ileum; the response to all doses was increased about 30% with no significant change in the EC50 value. Metronidazole and 5-ASA did not alter dose-response curves for the tonic contractile response to histamine or curves generated by the cumulative addition of histamine. Also, neither altered the positive chronotropic response on isolated right atria or the phasic contractile response on isolated segments of jejunum and duodenum to histamine or dimaprit. Likewise, neither altered dose-response curves for the direct action of carbamylcholine at muscarinic receptors or for the indirect actions of dimethylphenylpiperazinium on the ileum. The effects of 5-ASA or metronidazole on the response to histamine could be prevented as well as reversed by scopolamine or tetrodotoxin. The results suggest that metronidazole and 5-ASA enhance the actions of histamine and dimaprit on the ileum by an action on myenteric plexus neurons.

  20. The NprA nitroreductase required for 2,4-dinitrophenol reduction in Rhodobacter capsulatus is a dihydropteridine reductase.

    PubMed

    Pérez-Reinado, Eva; Roldán, María Dolores; Castillo, Francisco; Moreno-Vivián, Conrado

    2008-11-01

    The Rhodobacter capsulatus nprA gene codes for a putative nitroreductase. A recombinant His(6)-NprA protein was overproduced in Escherichia coli and purified by affinity chromatography. This protein contained FMN and showed nitroreductase activity with a wide range of nitroaromatic compounds, such as 2-nitrophenol, 2,4-dinitrophenol, 2,6-dinitrophenol, 2,4,6-trinitrophenol (picric acid), 2,4-dinitrobenzoate and 2,4-dinitrotoluene, and with the nitrofuran derivatives nitrofurazone and furazolidone. NADPH was the main electron donor and the ortho nitro group was preferably reduced to the corresponding amino derivative. The apparent K(m) values of NprA for NADPH, 2,4-dinitrophenol, picric acid and furazolidone were 40 microM, 78 microM, 72 microM and 83 microM, respectively, at pH and temperature optima (pH 6.5, 30 degrees C). Escherichia coli cells overproducing the NprA protein were much more sensitive to the prodrug 5-(aziridin-1-yl)-2,4-dinitrobenzamide (CB1954) used in cancer therapy than non-transformed cells. NprA showed the highest activity with the quinonoid form of 6,7-dimethyl-7,8-dihydropterine as substrate, so that NprA may be involved in the synthesis of tetrahydrobiopterin in R. capsulatus. Expression of a transcriptional nprA-lacZ gene fusion was induced by phenylalanine or tyrosine, but not by other amino acids like glutamate or alanine. Furthermore, both nitroreductase activity and phenylalanine assimilation were inhibited in vivo by ammonium. A mutant defective in the nprA gene showed better growth rate with Phe or Tyr as nitrogen source than the wild-type strain, although both strains showed similar growth in media with Glu or without added nitrogen. These results suggest that the NprA nitroreductase may act in vivo as a dihydropteridine reductase involved in aromatic amino acids metabolism.

  1. Controlled synthesis of uniform BiVO4 microcolumns and advanced visible-light-driven photocatalytic activity for the degradation of metronidazole-contained wastewater.

    PubMed

    Yu, Chongfei; Dong, Shuying; Feng, Jinglan; Sun, Jingyu; Hu, Limin; Li, Yukun; Sun, Jianhui

    2014-02-01

    Well-defined, uniform bismuth vanadate (BiVO4) microcolumns were synthesized through a refined hydrothermal route. During the fabrication process, a detailed orthogonal design on the synthetic conditions was performed, aiming to optimize the experimental parameters to produce BiVO4 materials (BiVO4 (Opt.)) with the most prominent visible-light-driven photocatalytic efficiency, where the catalytic activities of the synthesized materials were evaluated via the decolorization of methylene blue under visible light irradiation. The BiVO4 (Opt.) were then targetedly produced according to the determined optimal conditions and well characterized by X-ray diffraction, scanning electron microscopy, transmission electron microscopy, ultraviolet and visible diffuse-reflectance spectroscopy and photoluminescence spectroscopy. Compared with the commercial P25-TiO2 photocatalysts, the as-synthesized BiVO4 (Opt.) displayed superior visible-light-driven photocatalytic activities for the degradation of metronidazole-contained wastewater with the presence of H2O2. The degradation efficiency of metronidazole reached up to 70 % within 180 min, leading to a brief speculation on the possibly major steps of the visible-light-driven photocatalytic process. The current study provides a distinctive route to design novel shaped BiVO4 architectures with advanced photocatalytic capacities for the treatment of organic pollutants in the aqueous environment.

  2. Mechanical and thermal studies of metronidazole crystals

    NASA Astrophysics Data System (ADS)

    Ramukutty, S.; Jeyasudha, R.; Ramachandran, E.

    2013-10-01

    Single crystals of metronidazole have been synthesized natural evaporation method. The grown crystal has been confirmed using single crystal X-ray diffraction analysis. Mechanical behavior has been determined using Vickers hardness measurement. Work-hardening coefficient and Newtonian resistance pressure of the crystal have been estimated. Kinetic analysis of the thermogravimetric data has been carried out by using Coats-Redfern relation. Activation energy, frequency factor and order of reaction have been also calculated. The Arrhenius equation for metronidazole is k = 0.38 × 108 e-76.679/ RT mol-1 s-1. Thermodynamic parameters have been also determined.

  3. PnrA, a new nitroreductase-family enzyme in the TNT-degrading strain Pseudomonas putida JLR11.

    PubMed

    Caballero, Antonio; Lázaro, Juan J; Ramos, Juan L; Esteve-Núñez, Abraham

    2005-08-01

    Nitroreductases are a group of proteins that catalyse pyridine nucleotide-dependent reduction of nitroaromatics compounds, showing significant human health and environmental implications. In this study we have identified the nitroreductase-family enzymes PnrA and PnrB from the TNT-degrading strain Pseudomonas putida. The enzyme encoded by the pnrA gene was expressed in Escherichia coli, purified to homogeneity and shown to be a flavoprotein that used 2 mol of NADPH to reduce 1 mol of 2,4,6-trinitrotoluene (TNT) to 4-hydroxylamine-2,6-dinitrotoluene, using a ping-pong bi-bi mechanism. The PnrA enzyme also recognized as substrates as a number of other nitroaromatic compounds, i.e. 2,4-dinitrotoluene, 3-nitrotoluene, 3- and 4-nitrobenzoate, 3,5-dinitrobenzamide and 3,5-dinitroaniline expanding the substrates profile from previously described nitroreductases. However, TNT resulted to be the most efficient substrate examined according to the Vmax/Km parameter. Expression analysis of pnrA- and pnrB-mRNA isolated from cells growing on different nitrogen sources suggested that expression of both genes was constitutive and that its level of expression was relatively constant regardless of the growth substrate. This is in agreement with enzyme-specific activity determined with cells growing with different N-sources.

  4. The role of two putative nitroreductases, Frm2p and Hbn1p, in the oxidative stress response in Saccharomyces cerevisiae.

    PubMed

    de Oliveira, Iuri Marques; Zanotto-Filho, Alfeu; Moreira, José Cláudio Fonseca; Bonatto, Diego; Henriques, João Antonio Pêgas

    2010-02-01

    The nitroreductase family is comprised of a group of FMN- or FAD-dependent enzymes that are able to metabolize nitrosubstituted compounds using the reducing power of NAD(P)H. These nitroreductases can be found in bacterial species and, to a lesser extent, in eukaryotes. There is little information on the biochemical functions of nitroreductases. Some studies suggest their possible involvement in the oxidative stress response. In the yeast Saccharomyces cerevisiae, two nitroreductase proteins, Frm2p and Hbn1p, have been described. While Frm2p appears to act in the lipid signalling pathway, the function of Hbn1p is completely unknown. In order to elucidate the functions of Frm2p and Hbn1p, we evaluated the sensitivity of yeast strains, proficient and deficient in both oxidative stress proteins, for respiratory competence, antioxidant-enzyme activities, intracellular reactive oxygen species (ROS) production and lipid peroxidation. We found reduced basal activity of superoxide dismutase (SOD), ROS production, lipid peroxidation and petite induction and higher sensitivity to 4-nitroquinoline-oxide (4-NQO) and N-nitrosodiethylamine (NDEA), as well as higher basal activity of catalase (CAT) and glutathione peroxidase (GPx) and reduced glutathione (GSH) content in the single and double mutant strains frm2Delta and frm2Delta hbn1Delta. These strains exhibited less ROS accumulation and lipid peroxidation when exposed to peroxides, H(2)O(2) and t-BOOH. In summary, the Frm1p and Hbn1p nitroreductases influence the response to oxidative stress in S. cerevisae yeast by modulating the GSH contents and antioxidant enzymatic activities, such as SOD, CAT and GPx.

  5. Efficacy of New 5-Nitroimidazoles against Metronidazole-Susceptible and -Resistant Giardia, Trichomonas, and Entamoeba spp.

    PubMed Central

    Upcroft, Jacqueline A.; Campbell, Raymond W.; Benakli, Kamel; Upcroft, Peter; Vanelle, Patrice

    1999-01-01

    The efficacies of 12 5-nitroimidazole compounds and 1 previously described lactam-substituted nitroimidazole with antiparasitic activity, synthesized via SRN1 and subsequent reactions, were assayed against the protozoan parasites Giardia duodenalis, Trichomonas vaginalis, and Entamoeba histolytica. Two metronidazole-sensitive lines and two metronidazole-resistant lines of Giardia and one line each of metronidazole-sensitive and -resistant Trichomonas were tested. All except one of the compounds were as effective or more effective than metronidazole against Giardia and Trichomonas, but none was as effective overall as the previously described 2-lactam-substituted 5-nitroimidazole. None of the compounds was markedly more effective than metronidazole against Entamoeba. Significant cross-resistance between most of the drugs tested and metronidazole was evident among metronidazole-resistant lines of Giardia and Trichomonas. However, some drugs were lethal to metronidazole-resistant Giardia and had minimum lethal concentrations similar to that of metronidazole for drug-susceptible parasites. This study emphasizes the potential in developing new nitroimidazole drugs which are more effective than metronidazole and which may prove to be useful clinical alternatives to metronidazole. PMID:9869568

  6. Response to Metronidazole and Oxidative Stress Is Mediated through Homeostatic Regulator HsrA (HP1043) in Helicobacter pylori

    PubMed Central

    Olekhnovich, Igor N.; Vitko, Serhiy; Valliere, Meaghan

    2014-01-01

    Metronidazole (MTZ) is often used in combination therapies to treat infections caused by the gastric pathogen Helicobacter pylori. Resistance to MTZ results from loss-of-function mutations in genes encoding RdxA and FrxA nitroreductases. MTZ-resistant strains, when cultured at sub-MICs of MTZ (5 to 20 μg/ml), show dose-dependent defects in bacterial growth; depressed activities of many Krebs cycle enzymes, including pyruvate:ferredoxin oxidoreductase (PFOR); and low transcript levels of porGDAB (primer extension), phenotypes consistent with an involvement of a transcriptional regulator. Using a combination of protein purification steps, electrophoretic mobility shift assays (EMSAs), and mass spectrometry analyses of proteins bound to porG promoter sequences, we identified HP1043, an essential homeostatic global regulator (HsrA [for homeostatic stress regulator]). Competition EMSAs and supershift analyses with HsrA-enriched protein fractions confirmed specific binding to porGDAB and hsrA promoter sequences. Exposure to MTZ resulted in >10-fold decreases in levels of HsrA and in levels of the HsrA-regulated gene products PFOR and TlpB. Exposure to paraquat (PQ), hydrogen peroxide, or organic peroxides showed near equivalence with MTZ, revealing a common oxidative stress response pathway. Finally, direct superoxide dismutase (SOD) assays showed an inverse relationship between HsrA levels and SOD activity, suggesting that HsrA may serve as a repressor of sodB. As a homeostatic sentinel, HsrA appears to be ideally positioned to enable rapid shutdown of genes associated with metabolism and growth while activating (directly or indirectly) oxidative defense genes in response to low levels of toxic metabolites (MTZ or oxygen) before they reach DNA-damaging levels. PMID:24296668

  7. Successful treatment of refractory Trichomonas vaginalis infection using intravenous metronidazole.

    PubMed

    Hawkins, Isobel; Carne, Christopher; Sonnex, Christopher; Carmichael, Andrew

    2015-08-01

    Trichomonas vaginalis is a sexually transmitted protozoan infection resulting in a vulvo-vaginitis and altered vaginal discharge in symptomatic women. Since its introduction in the 1960 s, metronidazole has been the first-line drug for trichomonal infection. Other nitroimidazoles, such as tinidazole, are used as alternative regimens with similar activity but at a greater expense. Treatment failure usually represents patient non-compliance or reinfection, although metronidazole resistance has previously been documented. Sensitivity testing is currently not available in the UK. Patients with disease unresponsive to first-line treatments pose a major challenge, as therapeutic options are limited. This case looks at a patient with refractory disease over an 18-month period, where intravenous infusion of metronidazole resulted in cure after multiple previous therapy failures. There is limited evidence to endorse the use of intravenous metronidazole, and this case report provides further support for its efficacy.

  8. Metronidazole-resistant Trichomonas vaginalis.

    PubMed

    Forsgren, A; Forssman, L

    1979-10-01

    A 36-year-old woman with symptomatic metronidazole-resistant trichomonal vaginitis for 10 years had a total of 22 courses of treatment with either metronidazole or tinidazole according to different schedules. The minimum trichomonicidal concentration of metronidazole for the strain of Trichomonas vaginalis isolated from the patient was 160 microgram/ml compared with 1.25-10 microgram/ml for other freshly isolated strains. The former strain also showed a definitely decreased sensitivity to ornidazole and tinidazole (80 microgram/ml). The mechanisms behind the appearance of resistance in this clinical isolate are at present unknown and require further study from the theoretical as well as the therapeutic viewpoint.

  9. Metronidazole-Induced Cerebellar Toxicity

    PubMed Central

    Agarwal, Amit; Kanekar, Sangam; Sabat, Shyam; Thamburaj, Krishnamurthy

    2016-01-01

    Metronidazole is a very common antibacterial and antiprotozoal with wide usage across the globe, including the least developed countries. It is generally well-tolerated with a low incidence of serious side-effects. Neurological toxicity is fairly common with this drug, however majority of these are peripheral neuropathy with very few cases of central nervous toxicity reported. We report the imaging findings in two patients with cerebellar dysfunction after Metronidazole usage. Signal changes in the dentate and red nucleus were seen on magnetic resonance imaging in these patients. Most of the cases reported in literature reported similar findings, suggesting high predilection for the dentate nucleus in metronidazole induced encephalopathy. PMID:27127600

  10. Indirect electroreduction as pretreatment to enhance biodegradability of metronidazole.

    PubMed

    Saidi, I; Soutrel, I; Floner, D; Fourcade, F; Bellakhal, N; Amrane, A; Geneste, F

    2014-08-15

    The removal of metronidazole, a biorecalcitrant antibiotic, by coupling an electrochemical reduction with a biological treatment was examined. Electroreduction was performed in a home-made flow cell at -1.2V/SCE on graphite felt. After only one pass through the cell, analysis of the electrolyzed solution showed a total degradation of metronidazole. The biodegradability estimated from the BOD5/COD ratio increased from 0.07 to 0.2, namely below the value usually considered as the limit of biodegradability (0.4). In order to improve these results, indirect electrolysis of metronidazole was performed with a titanium complex known to reduce selectively nitro compounds into amine. The catalytic activity of the titanium complex towards electroreduction of metronidazole was shown by cyclic voltammetry analyses. Indirect electrolysis led to an improvement of the biodegradability from 0.07 to 0.42. To confirm the interest of indirect electroreduction to improve the electrochemical pretreatment, biological treatment was then carried out on activated sludge after direct and indirect electrolyses; different parameters were followed during the culture such as pH, TOC and metronidazole concentration. Both electrochemical processes led to a more efficient biodegradation of metronidazole compared with the single biological treatment, leading to an overall mineralization yield for the coupling process of 85%.

  11. A comparative study of metronidazole and sulfasalazine for active Crohn's disease: the cooperative Crohn's disease study in Sweden. I. Design and methodologic considerations.

    PubMed

    Rosén, A; Ursing, B; Alm, T; Bárány, F; Bergelin, I; Ganrot-Norlin, K; Hoevels, J; Huitfeldt, B; Järnerot, G; Krause, U; Krook, A; Lindström, B; Nordle, O

    1982-09-01

    The design and execution of the Cooperative Crohn's Disease Study in Sweden are described in this paper. A double-blind, double-dummy, crossover (2 X 4 mo) technique was used to compare the suppressive efficacy of metronidazole (0.4 g b.i.d.) and sulfasalazine (1.5 g b.i.d.). The number of randomized patients (78) presented approximately one-third of the available population. The Crohn's Disease Activity Index and the plasma level of orosomucoid were the main variables for clinical evaluation. Results were analyzed primarily in the first treatment period by ranking the clinical outcome of every patient according to a uniform and detailed scheme and applying Wilcoxon nonparametric statistics. The cross-over data only served as additional information. Thirty-six patients had had earlier and mostly positive experience with sulfasalazine. Repeated plasma drug analysis indicated good compliance. The blindness of the trial was tested and appeared satisfactory. The coordination of the trial proceeded as planned. A lack of full conformity in the electroimmunoassay of orosomucoid was taken care of satisfactorily.

  12. Method of controlled reduction of nitroaromatics by enzymatic reaction with oxygen sensitive nitroreductase enzymes

    DOEpatents

    Shah, Manish M.; Campbell, James A.

    1998-01-01

    A method for the controlled reduction of nitroaromatic compounds such as nitrobenzene and 2,4,6-trinitrotoluene by enzymatic reaction with oxygen sensitive nitroreductase enzymes, such as ferredoxin NADP oxidoreductase.

  13. Method of controlled reduction of nitroaromatics by enzymatic reaction with oxygen sensitive nitroreductase enzymes

    DOEpatents

    Shah, M.M.; Campbell, J.A.

    1998-07-07

    A method is described for the controlled reduction of nitroaromatic compounds such as nitrobenzene and 2,4,6-trinitrotoluene by enzymatic reaction with oxygen sensitive nitroreductase enzymes, such as ferredoxin NADP oxidoreductase. 6 figs.

  14. Delamanid is not metabolized by Salmonella or human nitroreductases: A possible mechanism for the lack of mutagenicity.

    PubMed

    Hanaki, Erina; Hayashi, Mikayo; Matsumoto, Makoto

    2017-03-01

    Nitro-containing compounds such as nitrofuran and nitroimidazole are drugs used for the treatment of infectious diseases. However, many of these nitro-containing drugs are positive in the bacterial reverse mutation assay (Ames test). The recently approved anti-multidrug-resistant tuberculosis (MDR-TB) drug, delamanid (Deltyba™; OPC-67683), a derivative of 4-nitroimidazole, was negative for mutagenicity in the Ames assay. In Salmonella typhimurium, mutagenicity of nitro compounds has been closely associated with the ability of nitroreductase to metabolize (degradation)these compounds. To explore the lack of mutagenicity for delamanid, we examined the initial metabolic rate and mutagenic-specific activity of a series of nitro compounds in S. typhimurium TA100. The order of maximum mutagenic-activity was nitrofuran > 2-nitroimidazole > 5-nitroimidazole ≥ 4-nitroimidazole, which is very similar to the order of initial metabolic rate, i.e., the Pearson's correlation coefficient (r = 0.85) showed a correlation between metabolic rate and mutagenic-activity. No metabolism of delamanid was detected even after 60 h of treatment. In addition, delamanid was not reduced by two human nitroreductases. These facts may explain the absence of genotoxicity of delamanid in both in vitro and in vivo tests.

  15. Crystal Structure of Reduced MsAcg, a Putative Nitroreductase from Mycobacterium smegmatis and a Close Homologue of Mycobacterium tuberculosis Acg

    PubMed Central

    Chauviac, François-Xavier; Bommer, Martin; Yan, Jun; Parkin, Gary; Daviter, Tina; Lowden, Philip; Raven, Emma L.; Thalassinos, Konstantinos; Keep, Nicholas H.

    2012-01-01

    This paper presents the structure of MsAcg (MSMEG_5246), a Mycobacterium smegmatis homologue of Mycobacterium tuberculosis Acg (Rv2032) in its reduced form at 1.6 Å resolution using x-ray crystallography. Rv2032 is one of the most induced genes under the hypoxic model of tuberculosis dormancy. The Acg family turns out to be unusual flavin mononucleotide (FMN)-binding proteins that have probably arisen by gene duplication and fusion from a classical homodimeric nitroreductase such that the monomeric protein resembles a classical nitroreductase dimer but with one active site deleted and the other active site covered by a unique lid. The FMN cofactor is not reduced by either NADH or NADPH, but the chemically reduced enzyme is capable of reduction of nitro substrates, albeit at no kinetic advantage over free FMN. The reduced enzyme is rapidly oxidized by oxygen but without any evidence for a radical state commonly seen in oxygen-sensitive nitroreductases. The presence of the unique lid domain, the lack of reduction by NAD(P)H, and the slow rate of reaction of the chemically reduced protein raises a possible alternative function of Acg proteins in FMN storage or sequestration from other biochemical pathways as part of the bacteria's adaptation to a dormancy state. PMID:23148223

  16. Biochemical characterization of NfsA, the Escherichia coli major nitroreductase exhibiting a high amino acid sequence homology to Frp, a Vibrio harveyi flavin oxidoreductase.

    PubMed Central

    Zenno, S; Koike, H; Kumar, A N; Jayaraman, R; Tanokura, M; Saigo, K

    1996-01-01

    We identified the nfsA gene, encoding the major oxygen-insensitive nitroreductase in Escherichia coli, and determined its position on the E. coli map to be 19 min. We also purified its gene product, NfsA, to homogeneity. It was suggested that NfsA is a nonglobular protein with a molecular weight of 26,799 and is associated tightly with a flavin mononucleotide. Its amino acid sequence is highly similar to that of Frp, a flavin oxidoreductase from Vibrio harveyi (B. Lei, M. Liu, S. Huang, and S.-C. Tu, J. Bacteriol. 176:3552-3558, 1994), an observation supporting the notion that E. coli nitroreductase and luminescent-bacterium flavin reductase families are intimately related in evolution. Although no appreciable sequence similarity was detected between two E. coli nitroreductases, NfsA and NfsB, NfsA exhibited a low level of the flavin reductase activity and a broad electron acceptor specificity similar to those of NfsB. NfsA reduced nitrofurazone by a ping-pong Bi-Bi mechanism possibly to generate a two-electron transfer product. PMID:8755878

  17. Reduction of quinones and nitroaromatic compounds by Escherichia coli nitroreductase A (NfsA): Characterization of kinetics and substrate specificity.

    PubMed

    Valiauga, Benjaminas; Williams, Elsie M; Ackerley, David F; Čėnas, Narimantas

    2017-01-15

    NfsA, a major FMN-associated nitroreductase of E. coli, reduces nitroaromatic compounds via consecutive two-electron transfers. NfsA has potential applications in the biodegradation of nitroaromatic environment pollutants, e.g. explosives, and is also of interest for the anticancer strategy gene-directed enzyme prodrug therapy. However, the catalytic mechanism of NfsA is poorly characterized. Here we examined the NADPH-dependent reduction of quinones (n = 16) and nitroaromatic compounds (n = 12) by NfsA. We confirmed a general "ping-pong" reaction scheme, and preliminary rapid reaction studies of the enzyme reduction by NADPH showed that this step is much faster than the steady-state turnover number, i.e., the enzyme turnover is limited by the oxidative half-reaction. The reactivity of nitroaromatic compounds (log kcat/Km) followed a linear dependence on their single-electron reduction potential (E(1)7), indicating a limited role for compound structure or active site flexibility in their reactivity. The reactivity of quinones was lower than that of nitroaromatics having similar E(1)7 values, except for the significantly enhanced reactivity of 2-OH-1,4-naphthoquinones, consistent with observations previously made for the group B nitroreductase of Enterobacter cloacae. We present evidence that the reduction of quinones by NfsA is most consistent with a single-step (H(-)) hydride transfer mechanism.

  18. Metronidazole hydrazone conjugates: Design, synthesis, antiamoebic and molecular docking studies.

    PubMed

    Ansari, Mohammad Fawad; Siddiqui, Shadab Miyan; Agarwal, Subhash M; Vikramdeo, Kunwar Somesh; Mondal, Neelima; Azam, Amir

    2015-09-01

    Metronidazole hydrazone conjugates (2-13) were synthesized and screened in vitro for antiamoebic activity against HM1: IMSS strain of Entamoeba histolytica. Six compounds were found to be better inhibitors of E. histolytica than the reference drug metronidazole. These compounds showed greater than 50-60% viability against HeLa cervical cancer cell line after 72 h treatment. Also, molecular docking study was undertaken on E. histolytica thioredoxin reductase (EhTHRase) protein which showed significant binding affinity in the active site. Out of the six actives, some of the compounds showed lipophilic characteristics.

  19. A metronidazole-resistant strain of Trichomonas vaginalis and its sensitivity to Go 10213.

    PubMed

    Ray, D K; Tendulkar, J S; Shrivastava, V B; Datta, A K; Nagarajan, K

    1984-10-01

    In the present study the comparative in-vitro and in-vivo efficacy of Go 10213 was compared with those of metronidazole, secnidazole, tinidazole, ornidazole and nimorazole against a metronidazole-resistant strain of T. vaginalis. Go 10213 was found to be superior in activity. It appears more promising than the drugs mentioned above on the basis of the evidence presented.

  20. Surface orientation control of site-specifically immobilized nitro-reductase (NfsB).

    PubMed

    Shen, Lei; Schroeder, McKenna; Ogorzalek, Tadeusz L; Yang, Pei; Wu, Fu-Gen; Marsh, E Neil G; Chen, Zhan

    2014-05-27

    We demonstrate the control of enzyme orientation for enzymes chemically immobilized on surfaces. Nitro-reductase (NfsB) has the ability to reduce a broad range of nitro-containing compounds and has potential applications in a broad range of areas including the detection and decomposition of explosives. The enzyme was tethered through unique surface cysteine residues to a self-assembled monolayer (SAM) terminated with maleimide groups. One cysteine was introduced close to the active site (V424C), and the other, at a remote site (H360C). The surface-tethered NfsB variants were interrogated by a combination of surface-sensitive sum frequency generation (SFG) vibrational spectroscopy and attenuated total reflection-Fourier transform infrared spectroscopy (ATR-FTIR) to determine how the mode of attachment altered the enzyme's orientation. The activities of the two immobilized NfsB variants were measured and can be well correlated to the deduced orientations. The relationships among enzyme engineering, surface immobilization, enzyme orientation, and enzyme activity were revealed.

  1. Two Atypical l-Cysteine-regulated NADPH-dependent Oxidoreductases Involved in Redox Maintenance, l-Cystine and Iron Reduction, and Metronidazole Activation in the Enteric Protozoan Entamoeba histolytica*

    PubMed Central

    Jeelani, Ghulam; Husain, Afzal; Sato, Dan; Ali, Vahab; Suematsu, Makoto; Soga, Tomoyoshi; Nozaki, Tomoyoshi

    2010-01-01

    We discovered novel catalytic activities of two atypical NADPH-dependent oxidoreductases (EhNO1/2) from the enteric protozoan parasite Entamoeba histolytica. EhNO1/2 were previously annotated as the small subunit of glutamate synthase (glutamine:2-oxoglutarate amidotransferase) based on similarity to authentic bacterial homologs. As E. histolytica lacks the large subunit of glutamate synthase, EhNO1/2 were presumed to play an unknown role other than glutamine/glutamate conversion. Transcriptomic and quantitative reverse PCR analyses revealed that supplementation or deprivation of extracellular l-cysteine caused dramatic up- or down-regulation, respectively, of EhNO2, but not EhNO1 expression. Biochemical analysis showed that these FAD- and 2[4Fe-4S]-containing enzymes do not act as glutamate synthases, a conclusion which was supported by phylogenetic analyses. Rather, they catalyze the NADPH-dependent reduction of oxygen to hydrogen peroxide and l-cystine to l-cysteine and also function as ferric and ferredoxin-NADP+ reductases. EhNO1/2 showed notable differences in substrate specificity and catalytic efficiency; EhNO1 had lower Km and higher kcat/Km values for ferric ion and ferredoxin than EhNO2, whereas EhNO2 preferred l-cystine as a substrate. In accordance with these properties, only EhNO1 was observed to physically interact with intrinsic ferredoxin. Interestingly, EhNO1/2 also reduced metronidazole, and E. histolytica transformants overexpressing either of these proteins were more sensitive to metronidazole, suggesting that EhNO1/2 are targets of this anti-amebic drug. To date, this is the first report to demonstrate that small subunit-like proteins of glutamate synthase could play an important role in redox maintenance, l-cysteine/l-cystine homeostasis, iron reduction, and the activation of metronidazole. PMID:20592025

  2. Structural and Mechanistic Insights into the Pseudomonas fluorescens 2-Nitrobenzoate 2-Nitroreductase NbaA.

    PubMed

    Kim, Yong-Hak; Song, Wooseok; Kim, Jin-Sik; Jiao, Li; Lee, Kangseok; Ha, Nam-Chul

    2015-08-01

    The bacterial 2-nitroreductase NbaA is the primary enzyme initiating the degradation of 2-nitrobenzoate (2-NBA), and its activity is controlled by posttranslational modifications. To date, the structure of NbaA remains to be elucidated. In this study, the crystal structure of a Cys194Ala NbaA mutant was determined to a 1.7-Å resolution. The substrate analog 2-NBA methyl ester was used to decipher the substrate binding site by inhibition of the wild-type NbaA protein. Tandem mass spectrometry showed that 2-NBA methyl ester produced a 2-NBA ester bond at the Tyr193 residue in the wild-type NbaA but not residues in the Tyr193Phe mutant. Moreover, covalent binding of the 2-NBA methyl ester to Tyr193 reduced the reactivity of the Cys194 residue on the peptide link. The Tyr193 hydroxyl group was shown to be essential for enzyme catalysis, as a Tyr193Phe mutant resulted in fast dissociation of flavin mononucleotide (FMN) from the protein with the reduced reactivity of Cys194. FMN binding to NbaA varied with solution NaCl concentration, which was related to the catalytic activity but not to cysteine reactivity. These observations suggest that the Cys194 reactivity is negatively affected by a posttranslational modification of the adjacent Tyr193 residue, which interacts with FMN and the substrate in the NbaA catalytic site.

  3. Structural and Mechanistic Insights into the Pseudomonas fluorescens 2-Nitrobenzoate 2-Nitroreductase NbaA

    PubMed Central

    Song, Wooseok; Kim, Jin-Sik; Jiao, Li; Lee, Kangseok

    2015-01-01

    The bacterial 2-nitroreductase NbaA is the primary enzyme initiating the degradation of 2-nitrobenzoate (2-NBA), and its activity is controlled by posttranslational modifications. To date, the structure of NbaA remains to be elucidated. In this study, the crystal structure of a Cys194Ala NbaA mutant was determined to a 1.7-Å resolution. The substrate analog 2-NBA methyl ester was used to decipher the substrate binding site by inhibition of the wild-type NbaA protein. Tandem mass spectrometry showed that 2-NBA methyl ester produced a 2-NBA ester bond at the Tyr193 residue in the wild-type NbaA but not residues in the Tyr193Phe mutant. Moreover, covalent binding of the 2-NBA methyl ester to Tyr193 reduced the reactivity of the Cys194 residue on the peptide link. The Tyr193 hydroxyl group was shown to be essential for enzyme catalysis, as a Tyr193Phe mutant resulted in fast dissociation of flavin mononucleotide (FMN) from the protein with the reduced reactivity of Cys194. FMN binding to NbaA varied with solution NaCl concentration, which was related to the catalytic activity but not to cysteine reactivity. These observations suggest that the Cys194 reactivity is negatively affected by a posttranslational modification of the adjacent Tyr193 residue, which interacts with FMN and the substrate in the NbaA catalytic site. PMID:26025888

  4. Formulation development and evaluation of metronidazole magnetic nanosuspension as a magnetic-targeted and polymeric-controlled drug delivery system

    NASA Astrophysics Data System (ADS)

    Latha, Subbiah; Selvamani, Palanisamy; Kumar, Chelladurai Senthil; Sharavanan, Palaniappan; Suganya, Govindan; Beniwal, Vijender Singh; Rao, Poduri Rama

    2009-05-01

    A nanosuspension of magnetically tagged metronidazole was developed by the solvent displacement method coupled with ultrasonication and was evaluated for its physicochemical properties. The drug release from metronidazole magnetic nanosuspension at pH 1.2 and 7.0 shows maximum correlation coefficient for zero order and Higuchi model, respectively. The anthelmintic activity of the formulated metronidazole magnetic nanosuspension was evaluated on Indian earthworms (Pheretima poi). Metronidazole magnetic nanosuspension at a dose of 10 and 50 mg/ml shortened by 31% and 34%, respectively, the mean time to death of the earthworms when compared against a non-magnetic metronidazole suspension. Thus, the developed metronidazole magnetic nanosuspension showed potent, controlled and targeted drug action and might be a good therapeutic avenue in combating infectious GI disorders.

  5. Effects of metronidazole (Flagyl) on the determination of serum ASAT on the SMA 12/60 Auto Analyser.

    PubMed

    Karlsen, R L; Kristiansen, G; Solberg, J H

    1983-04-01

    Therapeutic serum concentrations of metronidazole will lead to under-estimation of ASAT activity when a SMA 12/60 Auto Analyser is used. This interference is due to metronidazole entering the colorimeter through the dialyser membrane in the SMA 12/60 Auto Analyser. This drug is one of the few with a relatively high therapeutic serum concentration, absorbing light in the 340 nm range. Metronidazole will similarily affect other 340 nm methods (LDH, ALAT) available on the SMA 12/60. This interference with metronidazole on the SMA 12/60 can easily be solved by the introduction of a separate serum blank channel for the 340 nm methods.

  6. Real time detection of live microbes using a highly sensitive bioluminescent nitroreductase probe.

    PubMed

    Wong, Roger H F; Kwong, Thomas; Yau, Kwok-Hei; Au-Yeung, Ho Yu

    2015-03-14

    A highly sensitive and selective nitroreductase probe, showing a rapid and strong bioluminescence enhancement (>100-fold in 5 minutes), and its initial application in the real time detection of both Gram positive and Gram negative live bacteria and monitoring of their growth has been reported.

  7. Oxygen-Insensitive Nitroreductases NfsA and NfsB of Escherichia coli Function under Anaerobic Conditions as Lawsone-Dependent Azo Reductases

    PubMed Central

    Rau, Jörg; Stolz, Andreas

    2003-01-01

    Quinones can function as redox mediators in the unspecific anaerobic reduction of azo compounds by various bacterial species. These quinones are enzymatically reduced by the bacteria and the resulting hydroquinones then reduce in a purely chemical redox reaction the azo compounds outside of the cells. Recently, it has been demonstrated that the addition of lawsone (2-hydroxy-1,4-naphthoquinone) to anaerobically incubated cells of Escherichia coli resulted in a pronounced increase in the reduction rates of different sulfonated and polymeric azo compounds. In the present study it was attempted to identify the enzyme system(s) responsible for the reduction of lawsone by E. coli and thus for the lawsone-dependent anaerobic azo reductase activity. An NADH-dependent lawsone reductase activity was found in the cytosolic fraction of the cells. The enzyme was purified by column chromatography and the amino-terminal amino acid sequence of the protein was determined. The sequence obtained was identical to the sequence of an oxygen-insensitive nitroreductase (NfsB) described earlier from this organism. Subsequent biochemical tests with the purified lawsone reductase activity confirmed that the lawsone reductase activity detected was identical with NfsB. In addition it was proven that also a second oxygen-insensitive nitroreductase of E. coli (NfsA) is able to reduce lawsone and thus to function under adequate conditions as quinone-dependent azo reductase. PMID:12788749

  8. Ablation of central nervous system progenitor cells in transgenic rats using bacterial nitroreductase system.

    PubMed

    Kwak, Seung P; Malberg, Jessica E; Howland, David S; Cheng, Ke-Yi; Su, Jianying; She, Yin; Fennell, Myles; Ghavami, Afshin

    2007-05-01

    Specific ablation of central nervous system (CNS) progenitor cells in the brain of live animals is a powerful method to determine the functions of these cells and to reveal novel avenues for the treatment of several CNS-related disorders. To achieve this goal, we generated a line of transgenic rats expressing a bacterial enzyme, Escherichia coli nitroreductase gene (NTR), under control of the nestin promoter. In this system, NTR(+) cells are selectively eliminated upon application of prodrug CB1954, through activation of programmed cell death machineries. At 5 days of age, which is a time when cerebellar development is occurring, transgenic rats bearing the nestin-NTR/green fluorescent protein (GFP) gene are overtly normal and express NTR/GFP in neuronal stem cells, without any toxicity in these cells. The functional consequence of progenitor cell ablation was demonstrated by administering prodrug CB1954 into the cerebellum at this 5-day time point. Stem cell ablation in these neonates resulted in sensorimotor abnormalities, cerebellar degeneration, overall reduction in cerebellar seize, and manifestation of ataxia. In adult rats, GFP expression was not seen in the hippocampal progenitor cells and seen only at very low levels in the lateral ventricles, indicating a different NTR/GFP expression pattern between neonates and adults. In addition, application of CB1954 by intraventricular delivery reduced the number of 5-bromo-2'-deoxyuridine-labeled proliferating cells in the lateral ventricle but not hippocampus of NTR/GFP rats. These findings shows that targeted expression of NTR under a specific promoter might be of significant value in addressing the function of distinct cell population in vivo.

  9. Efficient Two-Photon Fluorescent Probe for Nitroreductase Detection and Hypoxia Imaging in Tumor Cells and Tissues.

    PubMed

    Zhang, Jing; Liu, Hong-Wen; Hu, Xiao-Xiao; Li, Jin; Liang, Li-Hui; Zhang, Xiao-Bing; Tan, Weihong

    2015-12-01

    Hypoxia plays an important role in tumor progression, and the development of efficient methods for monitoring hypoxic degree in living systems is of great biomedical importance. In the solid tumors, the nitroreductase level is directly corresponded with the hypoxic status. Many one-photon excited fluorescent probes have been developed for hypoxia imaging in tumor cells via the detection of nitroreductase level. However, two-photon excited probes are more suitable for bioimaging. In this work, a two-photon probe 1 for nitroreductase detection and hypoxic status monitoring in living tumor cells and tissues was reported for the first time. The detection is based on the fact that the nitro-group of probe 1 could be selectively reduced to an amino-group by nitroreductase in the presence of reduced NADH, following by a 1,6-rearrangement-elimination to release the fluorophore, resulting in the enhancement of fluorescence. The probe exhibited both one-photon and two-photon excited remarkable fluorescence enhancement (∼70-fold) for nitroreductase, which afforded a high sensitivity for nitroreductase, with a detection limit of 20 ng/mL observed. Moreover, the applications of the probe for fluorescent bioimaging of hypoxia in living cells and two-photon bioimaging in tissues were carried out, with tissue-imaging depths of 70-160 μm observed, which demonstrates its practical application in complex biosystems.

  10. Possible nephotoxic interaction of lithium and metronidazole

    SciTech Connect

    Teicher, M.H.; Altesman, R.I.; Cole, J.O.; Schatzberg, A.F.

    1987-06-26

    Several classes of drugs can promote renal retention of lithium and, occasionally, can induce lithium intoxication. The antimicrobial agent metronidazole hydrochloride (Flagyl I.V.) was also implicated in producing such a reaction in one woman. The authors describe two patients who experienced toxic reactions to lithium following brief use of metronidazole. However, in these two patients, in contrast to the previous case, the degree of acute intoxication was less severe and treatment with metronidazole was completed without apparent suspicion, but persistent signs of renal damage later emerged.

  11. Metronidazole-induced encephalopathy after prolonged metronidazole course for treatment of C. difficile colitis

    PubMed Central

    Godfrey, Mark S; Finn, Arkadiy; Zainah, Hadeel; Dapaah-Afriyie, Kwame

    2015-01-01

    A 65-year-old woman with a diagnosis of Clostridium difficile colitis undergoing prolonged treatment with metronidazole was admitted to hospital for altered mentation, slurred speech and weakness. She was diagnosed with metronidazole-induced encephalopathy, confirmed with brain MRI and improved when the offending agent was removed. This case report highlights encephalopathy as a complication of prolonged metronidazole treatment, which has become more common in clinical practice for the treatment of C. difficile infection. PMID:25596288

  12. Metronidazole-induced encephalopathy after prolonged metronidazole course for treatment of C. difficile colitis.

    PubMed

    Godfrey, Mark S; Finn, Arkadiy; Zainah, Hadeel; Dapaah-Afriyie, Kwame

    2015-01-16

    A 65-year-old woman with a diagnosis of Clostridium difficile colitis undergoing prolonged treatment with metronidazole was admitted to hospital for altered mentation, slurred speech and weakness. She was diagnosed with metronidazole-induced encephalopathy, confirmed with brain MRI and improved when the offending agent was removed. This case report highlights encephalopathy as a complication of prolonged metronidazole treatment, which has become more common in clinical practice for the treatment of C. difficile infection.

  13. PHARMACOKINETICS OF A SINGLE DOSE OF METRONIDAZOLE AFTER RECTAL ADMINISTRATION IN CAPTIVE ASIAN ELEPHANTS (ELEPHAS MAXIMUS).

    PubMed

    Sander, Samantha J; Siegal-Willott, Jessica L; Ziegler, Jessie; Lee, Elizabeth; Tell, Lisa; Murray, Suzan

    2016-03-01

    Metronidazole is a nitroimidazole antibacterial and antiprotozoal drug with bacteriocidal activity against a broad range of anaerobic bacteria. It is a recognized treatment for elephants diagnosed with anaerobic bacterial infection or protozoal disease or exhibiting signs of colonic impaction, diarrhea, and colic. This study evaluated the pharmacokinetics of rectally administered metronidazole (15 mg/kg) in five adult female Asian elephants (Elephas maximus). Serum samples were collected from each animal for 96 hr after rectal administration of metronidazole. Serum concentrations of metronidazole and its primary metabolite, hydroxymetronidazole, were measured via ultraperformance liquid chromatography. Data were analyzed via a noncompartmental pharmacokinetic approach. Results indicated that serum levels of metronidazole were quantifiable at the 0.25 hr time point and absent in all elephants by the 96 hr time point. The serum peak concentration (mean ± SD, 13.15 ± 2.59 μg/ml) and area under the curve from time 0 to infinity (mean ± SD, 108.79 ± 24.77 hr × μg/ml) were higher than that reported in domestic horses after similar usage. Concurrently, the time of maximum serum concentration (mean ± SD, 1.2 ± 0.45 hr) and terminal elimination half-life (harmonic mean ± pseudo-SD, 7.85 ± 0.93 hr) were longer when compared to equine reports. Rectal administration of metronidazole was well tolerated and rapidly absorbed in all study elephants. Based on the findings in this study, metronidazole administered at a single dose of 15 mg/kg per rectum in the Asian elephant is likely to result in serum concentrations above 4 μg/ml for 8 hr and above 2 μg/ml for 24 hr after treatment is administered. Dosing recommendations should reflect the mean inhibitory concentration of metronidazole for each pathogen.

  14. Trichomonas vaginalis flavin reductase 1 and its role in metronidazole resistance.

    PubMed

    Leitsch, David; Janssen, Brian D; Kolarich, Daniel; Johnson, Patricia J; Duchêne, Michael

    2014-01-01

    The enzyme flavin reductase 1 (FR1) from Trichomonas vaginalis, formerly known as NADPH oxidase, was isolated and identified. Flavin reductase is part of the antioxidative defence in T. vaginalis and indirectly reduces molecular oxygen to hydrogen peroxide via free flavins. Importantly, a reduced or absent flavin reductase activity has been reported in metronidazole-resistant T. vaginalis, resulting in elevated intracellular oxygen levels and futile cycling of metronidazole. Interestingly, FR1 has no close homologue in any other sequenced genome, but seven full-length and three truncated isoforms exist in the T. vaginalis genome. However, out of these, only FR1 has an affinity for flavins, i.e. FMN, FAD and riboflavin, which is high enough to be of physiological relevance. Although there are no relevant changes in the gene sequence or any alterations of the predicted FR1-mRNA structure in any of the strains studied, FR1 is not expressed in highly metronidazole-resistant strains. Transfection of a metronidazole-resistant clinical isolate (B7268), which does not express any detectable amounts of FR, with a plasmid bearing a functional FR1 gene nearly completely restored metronidazole sensitivity. Our results indicate that FR1 has a significant role in the emergence of metronidazole resistance in T. vaginalis.

  15. Evaluation of polycaprolactone matrices for the intravaginal delivery of metronidazole in the treatment of bacterial vaginosis.

    PubMed

    Pathak, Meenakshi; Turner, Mark; Palmer, Cheryn; Coombes, Allan G A

    2014-09-01

    Microporous, poly (ɛ-caprolactone) (PCL) matrices loaded with the antibacterial, metronidazole were produced by rapidly cooling suspensions of drug powder in PCL solutions in acetone. Drug incorporation in the matrices increased from 2.0% to 10.6% w/w on raising the drug loading of the PCL solution from 5% to 20% w/w measured with respect to the PCL content. Drug loading efficiencies of 40-53% were obtained. Rapid 'burst release' of 35-55% of the metronidazole content was recorded over 24 h when matrices were immersed in simulated vaginal fluid (SVF), due to the presence of large amounts of drug on matrix surface as revealed by Raman microscopy. Gradual release of around 80% of the drug content occurred over the following 12 days. Metronidazole released from PCL matrices in SVF retained antimicrobial activity against Gardnerella vaginalis in vitro at levels up to 97% compared to the free drug. Basic modelling predicted that the concentrations of metronidazole released into vaginal fluid in vivo from a PCL matrix in the form of an intravaginal ring would exceed the minimum inhibitory concentration of metronidazole against G. vaginalis. These findings recommend further investigation of PCL matrices as intravaginal devices for controlled delivery of metronidazole in the treatment and prevention of bacterial vaginosis.

  16. Deficiency of the ferrous iron transporter FeoAB is linked with metronidazole resistance in Bacteroides fragilis

    PubMed Central

    Veeranagouda, Yaligara; Husain, Fasahath; Boente, Renata; Moore, Jane; Smith, C. Jeffrey; Rocha, Edson R.; Patrick, Sheila; Wexler, Hannah M.

    2014-01-01

    Background Metronidazole is the most commonly used antimicrobial for Bacteroides fragilis infections and is recommended for prophylaxis of colorectal surgery. Metronidazole resistance is increasing and the mechanisms of resistance are not clear. Methods A transposon mutant library was generated in B. fragilis 638R (BF638R) to identify the genetic loci associated with resistance to metronidazole. Results Thirty-two independently isolated metronidazole-resistant mutants had a transposon insertion in BF638R_1421 that encodes the ferrous transport fusion protein (feoAB). Deletion of feoAB resulted in a 10-fold increased MIC of metronidazole for the strain. The metronidazole MIC for the feoAB mutant was similar to that for the parent strain when grown on media supplemented with excess iron, suggesting that the increase seen in the MIC of metronidazole was due to reduced cellular iron transport in the feoAB mutant. The furA gene repressed feoAB transcription in an iron-dependent manner and disruption of furA resulted in constitutive transcription of feoAB, regardless of whether or not iron was present. However, disruption of feoAB also diminished the capacity of BF638R to grow in a mouse intraperitoneal abscess model, suggesting that inorganic ferrous iron assimilation is essential for B. fragilis survival in vivo. Conclusions Selection for feoAB mutations as a result of metronidazole treatment will disable the pathogenic potential of B. fragilis and could contribute to the clinical efficacy of metronidazole. While mutations in feoAB are probably not a direct cause of clinical resistance, this study provides a key insight into intracellular metronidazole activity and the link with intracellular iron homeostasis. PMID:25028451

  17. Bi-functionalization of a calcium phosphate-coated titanium surface with slow-release simvastatin and metronidazole to provide antibacterial activities and pro-osteodifferentiation capabilities.

    PubMed

    Liu, Yunsong; Zhang, Xiao; Liu, Yang; Jin, Xiaoxiao; Fan, Cong; Ye, Hongqiang; Ou, Meng'en; Lv, Longwei; Wu, Gang; Zhou, Yongsheng

    2014-01-01

    Coating the surface of titanium implants or other bone graft substitute materials with calcium phosphate (Ca-P) crystals is an effective way to enhance the osteoconduction of the implants. Ca-P coating alone cannot confer pro-osteodifferentiation and antibacterial capabilities on implants; however, it can serve as a carrier for biological agents which could improve the performance of implants and bone substitutes. Here, we constructed a novel, bi-functional Ca-P coating with combined pro-osteodifferentiation and antibacterial capabilities. Different concentrations of metronidazole (MNZ) and simvastatin (SIM) were integrated into biomimetic Ca-P coatings on the surface of titanium disks. The biological effects of this bi-functional biomimetic coating on human bone marrow mesenchymal stem cells (hBMMSCs), human adipose derived stromal cells (hASCs), and Porphyromonas gingivalis were assessed in vitro. We observed that Ca-P coatings loaded with both SIM and MNZ display favorable release kinetics without affecting cell proliferation or attachment. In the inhibition zone test, we found that the bi-functional coating showed lasting antibacterial effects when incubated with Porphyromonas gingivalis for 2 and 4 days. Moreover, the osteodifferentiation of hBMMSCs and hASCs were increased when cultured on this bi-functional coating for 7 and 14 days. Both drugs were loaded onto the Ca-P coating at specific concentrations (10(-5) M SIM; 10(-2) M MNZ) to achieve optimal release kinetics. Considering the safety, stability and low cost of SIM and MNZ, this novel bi-functional Ca-P coating technique represents a promising method to improve the performance of metal implants or other bone substitute materials, and can theoretically be easily translated to clinical applications.

  18. The Nitroreductase System of Inducible Targeted Ablation Facilitates Cell-specific Regenerative Studies in Zebrafish

    PubMed Central

    White, David T.; Mumm, Jeff S.

    2013-01-01

    At the turn of the 20th century, classical regenerative biology – the study of organismal/tissue/limb regeneration in animals such as crayfish, snails, and planaria – garnered much attention. However, scientific luminaries such as Thomas Hunt Morgan eventually turned to other fields after concluding that inquiries into regenerative mechanisms were largely intractable beyond observational intrigues. The field of regeneration has enjoyed a resurgence in research activity at the turn of the 21st century, in large part due to “the promise” of cultured stem cells regarding reparative therapeutic approaches. Additionally, genomics-based methods that allow sophisticated genetic/molecular manipulations to be carried out in nearly any species have extended organismal regenerative biology well beyond observational limits. Throughout its history, complex paradigms such as limb regeneration – involving multiple tissue/cell types, thus, potentially multiple stem cell subtypes – have predominated the regenerative biology field. Conversely, cellular regeneration – the replacement of specific cell types – has been studied from only a few perspectives (predominantly muscle and mechanosensory hair cells). Yet, many of the degenerative diseases that regenerative biology hopes to address involve the loss of individual cell types; thus, a primary emphasis of the embryonic/induced stem cell field is defining culture conditions which promote cell-specific differentiation. Here we will discuss recent methodological approaches that promote the study of cell-specific regeneration. Such paradigms can reveal how the differentiation of specific cell types and regenerative potential of discrete stem cell niches are regulated. In particular, we will focus on how the nitroreductase (NTR) system of inducible targeted cell ablation facilitates: 1) large-scale genetic and chemical screens for identifying factors that regulate regeneration and, 2) in vivo time-lapse imaging

  19. Metronidazole in prevention and treatment of bacteroides infections after appendicectomy.

    PubMed Central

    Willis, A T; Ferguson, I R; Jones, P H; Phillips, K D; Tearle, P V; Berry, R B; Fiddian, R V; Graham, D F; Harland, D H; Innes, D B; Mee, W M; Rothwell-Jackson, R L; Sutch, I; Kilbey, C; Edwards, D

    1976-01-01

    The frequency of non-clostridial anaerobic infection was studied in 95 patients who had undergone acute appendicectomy: 49 received prophylactic metronidazole and 46 received placebo. Anaerobic infection did not develop in any of the metronidazole-treated patients, but infections did develop in nine (19%) of the 46 controls. Metronidazole is conveniently administered by suppository to patients who cannot take oral drugs. Five patients with intra-abdominal infections caused by non-clostridial anaerobes were successfully treated with metronidazole. PMID:764935

  20. Metronidazole and spiramycin therapy of mixed Bacteroides spp. and Neisseria gonorrhoeae infection in mice.

    PubMed

    Brook, I

    1989-01-01

    The in vitro and in vivo activity of metronidazole and spiramycin, used singly or in combination, was tested in the eradication of infection caused by Bacteroides spp. and Neisseria gonorrhoeae alone or in combination. The in vitro tests consisted of determinations of the minimal inhibitory concentrations (MIC), carried out with or without the addition of a constant amount of the other antimicrobials. The MIC of both Bacteroides bivius and Bacteroides fragilis for metronidazole were significantly reduced by the addition of spiramycin (from 0.5 to 0.125 micrograms/ml). The in vivo tests were carried out in mice and consisted of measurements of the effects of the antimicrobial agents on the bacterial contents of abscesses induced by subcutaneous injection of bacterial suspension. Synergism between metronidazole and spiramycin was noted against Bacteroides spp. in abscesses caused by either Bacteroides spp. alone, or in combination with N. gonorrhoeae. Furthermore, an additional reduction in the number of N gonorrhoeae was noted in mixed infection with Bacteroides that was treated with metronidazole alone. This study demonstrates the in vitro and in vivo efficacy of the combination of metronidazole and spiramycin in the treatment of infections caused by either Bacteroides spp. alone or in combination with N. gonorrhoeae.

  1. Metronidazole: newly recognized cause of autonomic neuropathy.

    PubMed

    Hobson-Webb, Lisa D; Roach, E Steve; Donofrio, Peter D

    2006-05-01

    Metronidazole is a commonly used antibiotic prescribed for the treatment of anaerobic and protozoal infections of the gastrointestinal and genitourinary tracts. It is associated with numerous neurologic complications, including peripheral neuropathy. Neuropathy is typically detected in patients on chronic therapy, although it has been documented in those taking large doses for acute infections. Numerous case reports have been published describing motor and sensory neuropathy, yet autonomic neuropathy has not been described with metronidazole use. A previously healthy 15-year-old girl presented with complaints of burning pain in her feet following a short course of metronidazole for vaginitis. She could obtain pain relief only by submerging her feet in ice water. Examination revealed cold and swollen lower extremities that became erythematous and very warm when removed from the ice water. Temperature perception was reduced to the upper third of the shin bilaterally. Deep tendon reflexes and strength were preserved. Nerve conduction studies demonstrated a peripheral neuropathy manifested by reduced sensory nerve and compound muscle action potentials. Reproducible sympathetic skin potential responses could not be obtained in the hand and foot, providing evidence of a concurrent autonomic neuropathy. A thorough evaluation revealed no other cause for her condition. Repeated nerve conduction studies and sympathetic skin potentials returned to normal over the course of 6 months, paralleling the patient's clinical improvement. Metronidazole is a potential cause of reversible autonomic neuropathy.

  2. Exploratory Investigation of Bacteroides fragilis Transcriptional Response during In vitro Exposure to Subinhibitory Concentration of Metronidazole

    PubMed Central

    de Freitas, Michele C. R.; Resende, Juliana A.; Ferreira-Machado, Alessandra B.; Saji, Guadalupe D. R. Q.; de Vasconcelos, Ana T. R.; da Silva, Vânia L.; Nicolás, Marisa F.; Diniz, Cláudio G.

    2016-01-01

    Bacteroides fragilis, member from commensal gut microbiota, is an important pathogen associated to endogenous infections and metronidazole remains a valuable antibiotic for the treatment of these infections, although bacterial resistance is widely reported. Considering the need of a better understanding on the global mechanisms by which B. fragilis survive upon metronidazole exposure, we performed a RNA-seq transcriptomic approach with validation of gene expression results by qPCR. Bacteria strains were selected after in vitro subcultures with subinhibitory concentration (SIC) of the drug. From a wild type B. fragilis ATCC 43859 four derivative strains were selected: first and fourth subcultures under metronidazole exposure and first and fourth subcultures after drug removal. According to global gene expression analysis, 2,146 protein coding genes were identified, of which a total of 1,618 (77%) were assigned to a Gene Ontology term (GO), indicating that most known cellular functions were taken. Among these 2,146 protein coding genes, 377 were shared among all strains, suggesting that they are critical for B. fragilis survival. In order to identify distinct expression patterns, we also performed a K-means clustering analysis set to 15 groups. This analysis allowed us to detect the major activated or repressed genes encoding for enzymes which act in several metabolic pathways involved in metronidazole response such as drug activation, defense mechanisms against superoxide ions, high expression level of multidrug efflux pumps, and DNA repair. The strains collected after metronidazole removal were functionally more similar to those cultured under drug pressure, reinforcing that drug-exposure lead to drastic persistent changes in the B. fragilis gene expression patterns. These results may help to elucidate B. fragilis response during metronidazole exposure, mainly at SIC, contributing with information about bacterial survival strategies under stress conditions in their

  3. Exploratory Investigation of Bacteroides fragilis Transcriptional Response during In vitro Exposure to Subinhibitory Concentration of Metronidazole.

    PubMed

    de Freitas, Michele C R; Resende, Juliana A; Ferreira-Machado, Alessandra B; Saji, Guadalupe D R Q; de Vasconcelos, Ana T R; da Silva, Vânia L; Nicolás, Marisa F; Diniz, Cláudio G

    2016-01-01

    Bacteroides fragilis, member from commensal gut microbiota, is an important pathogen associated to endogenous infections and metronidazole remains a valuable antibiotic for the treatment of these infections, although bacterial resistance is widely reported. Considering the need of a better understanding on the global mechanisms by which B. fragilis survive upon metronidazole exposure, we performed a RNA-seq transcriptomic approach with validation of gene expression results by qPCR. Bacteria strains were selected after in vitro subcultures with subinhibitory concentration (SIC) of the drug. From a wild type B. fragilis ATCC 43859 four derivative strains were selected: first and fourth subcultures under metronidazole exposure and first and fourth subcultures after drug removal. According to global gene expression analysis, 2,146 protein coding genes were identified, of which a total of 1,618 (77%) were assigned to a Gene Ontology term (GO), indicating that most known cellular functions were taken. Among these 2,146 protein coding genes, 377 were shared among all strains, suggesting that they are critical for B. fragilis survival. In order to identify distinct expression patterns, we also performed a K-means clustering analysis set to 15 groups. This analysis allowed us to detect the major activated or repressed genes encoding for enzymes which act in several metabolic pathways involved in metronidazole response such as drug activation, defense mechanisms against superoxide ions, high expression level of multidrug efflux pumps, and DNA repair. The strains collected after metronidazole removal were functionally more similar to those cultured under drug pressure, reinforcing that drug-exposure lead to drastic persistent changes in the B. fragilis gene expression patterns. These results may help to elucidate B. fragilis response during metronidazole exposure, mainly at SIC, contributing with information about bacterial survival strategies under stress conditions in their

  4. A reprofiled drug, auranofin, is effective against metronidazole-resistant Giardia lamblia.

    PubMed

    Tejman-Yarden, Noa; Miyamoto, Yukiko; Leitsch, David; Santini, Jennifer; Debnath, Anjan; Gut, Jiri; McKerrow, James H; Reed, Sharon L; Eckmann, Lars

    2013-05-01

    Giardiasis is one of the most common causes of diarrheal disease worldwide. Treatment is primarily with 5-nitro antimicrobials, particularly metronidazole. Resistance to metronidazole has been described, and treatment failures can occur in up to 20% of cases, making development of alternative antigiardials an important goal. To this end, we have screened a chemical library of 746 approved human drugs and 164 additional bioactive compounds for activity against Giardia lamblia. We identified 56 compounds that caused significant inhibition of G. lamblia growth and attachment. Of these, 15 were previously reported to have antigiardial activity, 20 were bioactive but not approved for human use, and 21 were drugs approved for human use for other indications. One notable compound of the last group was the antirheumatic drug auranofin. Further testing revealed that auranofin was active in the low (4 to 6)-micromolar range against a range of divergent G. lamblia isolates representing both human-pathogenic assemblages A and B. Most importantly, auranofin was active against multiple metronidazole-resistant strains. Mechanistically, auranofin blocked the activity of giardial thioredoxin oxidoreductase, a critical enzyme involved in maintaining normal protein function and combating oxidative damage, suggesting that this inhibition contributes to the antigiardial activity. Furthermore, auranofin was efficacious in vivo, as it eradicated infection with different G. lamblia isolates in different rodent models. These results indicate that the approved human drug auranofin could be developed as a novel agent in the armamentarium of antigiardial drugs, particularly against metronidazole-resistant strains.

  5. 78 FR 19271 - Draft Guidance for Industry on Bioequivalence Recommendations for Metronidazole Vaginal Gel...

    Federal Register 2010, 2011, 2012, 2013, 2014

    2013-03-29

    ... Recommendations for Metronidazole Vaginal Gel; Availability AGENCY: Food and Drug Administration, HHS. ACTION... guidance for industry entitled ``Bioequivalence Recommendations for Metronidazole Vaginal Gel.'' The... abbreviated new drug applications (ANDAs) for metronidazole vaginal gel. DATES: Although you can comment...

  6. Uptake of metronidazole in Artemia at different developmental life stages.

    PubMed

    Rodriguez, Loretta; Livengood, Elisa J; Miles, Richard D; Chapman, Frank A

    2011-06-01

    The purpose of this study was to examine the capacity of live brine shrimp Artemia spp. to accumulate metronidazole at different developmental life stages. Metronidazole is used in fish as an antiparasitic medication. An effective drug delivery method is to enrich the Artemia with metronidazole and offer them as live feed to the infected fish, usually ornamental species and other small fishes. Artemia cysts were hatched and then soaked in a metronidazole solution (0.05%) at instars 1-3 of larval development. Our findings indicated that Artemia were able to accumulate metronidazole at levels considered therapeutic to other animals and humans (25-100 mg/kg). However, the levels varied depending on the stage of larval development. Artemia accumulated the highest levels of metronidazole (137-143 mg/kg) when they started filter feeding (instar 2), whereas newly hatched Artemia (instar 1) contained the lowest level (85 mg/kg). Based on this study and a review of the literature, a new protocol recommended for enriching Artemia with metronidazole consists of soaking the Artemia in a 0.05% metronidazole solution for 3 h at room temperature. Because metronidazole is relatively insoluble in water, it must first be dissolved in warm water with continuous stirring.

  7. Novel aryl carbamate derivatives of metronidazole as potential antiamoebic agents.

    PubMed

    Hayat, Faisal; Wahedi, Hussain Mustatab; Park, Seonghyeok; Tariq, Saba; Azam, Amir; Shin, Dongyun

    2016-01-01

    A series of novel aryl carbamate derivatives of metronidazole (MNZ) were designed, synthesized, and screened for antiamoebic activity. As compared to MNZ, most of the derivatives exhibited moderate to excellent activity against the HM1:IMSS strain of Entamoeba histolytica. Compounds 7, 14, 16, 19, and 21 exhibited the most promising antiamoebic activity with IC50 values of 0.24, 0.08, 0.26, 0.26, and 0.15 μM, respectively, compared to that of MNZ (1.78 μM). Moreover, from the toxicological studies of these compounds on human melanocytes, the melan-a cell line revealed that the potent compounds are nontoxic at concentrations ranging from 2.5 to 50 μM.

  8. Characterization of a nitroreductase with selective nitroreduction properties in the food and intestinal lactic acid bacterium Lactobacillus plantarum WCFS1.

    PubMed

    Guillén, Hugo; Curiel, Jose Antonio; Landete, José María; Muñoz, Rosario; Herraiz, Tomás

    2009-11-11

    Nitroreductases reduce nitroaromatic compounds and other oxidants in living organisms, having interesting implications in environmental and human health. A putative nitrobenzoate reductase encoding gene (lp_0050) was recently annotated in the completed DNA sequence of lactic acid bacterium Lactobacillus plantarum WCFS1 strain. In this research, this L. plantarum gene was cloned and expressed, and the corresponding protein (PnbA) was biochemically characterized. This L. plantarum PnbA reductase is a 216 amino acid residue FMN-flavoprotein, which exhibits 23% identity with Pseudomonas putida and Ralstonia eutropha nitroreductases and <11% identity with those from enterobacteria such as E. cloacae . This reductase also showed 32-43% identity (65-72% similarity) to predicted PnbA proteins from other lactic acid bacteria. It utilized a wide range of electron acceptors including dichlorophenolindophenol (DCPIP), nitroblue tetrazolium (NBT), ferricyanide, and quinones (menadione, benzoquinone), but not pyridinium cations (paraquat and N-methyl-beta-carbolines), and it was inhibited by dicoumarol and diphenyliodonium. HPLC-MS and spectroscopic data showed that it specifically catalyzed the reduction of the 4-nitroaromatic group to the corresponding hydroxylamine in the presence of NAD(P)H. Kinetics parameters (V(max) and K(m)) showed a higher efficiency for the reduction of 2,4-dinitrobenzoate than for the reduction of 4-nitrobenzoate. It was chemoselective for the reduction of 4-nitrobenzoates, being unable to reduce other nitroaromatics. Then, L. plantarum PnbA reductase might be more specific than other microbial nitroreductases that reduce a wider range of nitroaromatic compounds. The physiological and functional role of nitroreductases remain unknown; however, their presence in lactic acid bacteria widely occurring in foods and the human intestinal tract should be of further interest.

  9. Synthesis, molecular docking and biological evaluation of metronidazole derivatives containing piperazine skeleton as potential antibacterial agents.

    PubMed

    Wang, She-Feng; Yin, Yong; Qiao, Fang; Wu, Xun; Sha, Shao; Zhang, Li; Zhu, Hai-Liang

    2014-04-15

    Metronidazole has a broad-spectrum antibacterial activity. Hereby a series of novel metronidazole derivatives were designed and synthesized based on nitroimidazole scaffold in order to find some more potent antibacterial drugs. For these compounds which were reported for the first time, their antibacterial activities against Escherichia coli, Pseudomonas aeruginosa, Bacillus subtilis and Staphylococcus aureus were tested. These compounds showed good antibacterial activities against Gram-positive strains. Compound 4m represented the most potent antibacterial activity against S. aureus ATCC 25923 with MIC of 0.003 μg/mL and it showed the most potent activity against S. aureus TyrRS with IC50 of 0.0024 μM. Molecular docking of 4m into S. aureus tyrosyl-tRNA synthetase active site were also performed to determine the probable binding mode.

  10. A two-photon fluorescent probe for nitroreductase imaging in living cells, tissues and zebrafish under hypoxia conditions.

    PubMed

    Zhai, Baoping; Hu, Wei; Sun, Jinyu; Chi, Siyu; Lei, Yidi; Zhang, Fang; Zhong, Cheng; Liu, Zhihong

    2017-04-04

    A two-photon fluorescent probe FNTR for nitroreductase was synthesized by using 9,9-dimethyl-2-acetyl-fluoren-7-methylamino (1) as a two-photon fluorophore and a p-nitrobenzyl carbamate group as a recognition domain for nitroreductase (NTR). The probe and the fluorophore were tested under one- and two-photon modes respectively. After reacting with nitroreductase, FNTR had a 130-fold fluorescence enhancement at 563 nm in 10 min and the maximal two-photon action cross-section value was detected as 66 GM at 750 nm. The probe showed a high sensitivity with a detection limit as low as 23.67 ng ml(-1), high selectivity, low cytotoxicity and good photostability. In the presence of reduced nicotinamide adenine dinucleotide (NADH), endogenous NTR was detected in living cells, tissues and zebrafish. Cobalt chloride was used to induce chemical hypoxia to produce NTR, which generated enhanced fluorescence in cells and tumor tissues. Finally, two-photon fluorescence imaging of NTR was achieved in zebrafish at a penetration depth of up to 200 μm.

  11. Metronidazole-induced encephalopathy in a patient with Crohn's disease

    PubMed Central

    Kim, Jihye; Park, Jae Yong; Hong, Seung Wook; Lee, Joo Young; Kang, Jin Woo; Hwang, Seongjun; Ko, Sang-Bae; Im, Jong Pil; Kim, Joo Sung

    2017-01-01

    Metronidazole is a widely used antibiotic for the treatment of anaerobic bacterial infections. Metronidazole-induced encephalopathy (MIEP) is a rare but potentially reversible disease. The mechanism of MIEP remains unclear, and differences in the neurotoxic effects of oral versus intravenous (IV) metronidazole administration have not yet been determined. We report the case of a Crohn's disease (CD) patient who experienced encephalopathy immediately after a single IV dose of metronidazole following long-term exposure to the oral form of the drug. The 64-year-old man with intractable CD experienced a sudden change in mental status, aphasia, and muscle weakness after IV administration of metronidazole. He had previously taken metronidazole orally for 13 years and received intermittent IV metronidazole treatments for CD exacerbation. Brain magnetic resonance imaging (MRI) showed high-intensity signals in the bilateral medial thalamus and the midbrain and pontine tegmentum on fluid-attenuated inversion recovery images. After discontinuation of metronidazole, the high-intensity brain MRI signals resolved and the patient's mental status dramatically improved; however, the patient exhibited mild cognitive dysfunction 2 months after the onset of encephalopathy. PMID:28239323

  12. Gastrointestinal localization of metronidazole by a lactobacilli-inspired tetramic acid motif improves treatment outcomes in the hamster model of Clostridium difficile infection

    PubMed Central

    Cherian, Philip T.; Wu, Xiaoqian; Yang, Lei; Scarborough, Jerrod S.; Singh, Aman P.; Alam, Zahidul A.; Lee, Richard E.; Hurdle, Julian G.

    2015-01-01

    Objectives Metronidazole, a mainstay treatment for Clostridium difficile infection (CDI), is often ineffective for severe CDI. Whilst this is thought to arise from suboptimal levels of metronidazole in the colon due to rapid absorption, empirical validation is lacking. In contrast, reutericyclin, an antibacterial tetramic acid from Lactobacillus reuteri, concentrates in the gastrointestinal tract. In this study, we modified metronidazole with reutericyclin's tetramic acid motif to obtain non-absorbed compounds, enabling assessment of the impact of pharmacokinetics on treatment outcomes. Methods A series of metronidazole-bearing tetramic acid substituents were synthesized and evaluated in terms of anti-C. difficile activities, gastric permeability, in vivo pharmacokinetics, efficacy in the hamster model of CDI and mode of action. Results Most compounds were absorbed less than metronidazole in cell-based Caco-2 permeability assays. In hamsters, lead compounds compartmentalized in the colon rather than the bloodstream with negligible levels detected in the blood, in direct contrast with metronidazole, which was rapidly absorbed into the blood and was undetectable in caecum. Accordingly, four leads were more efficacious (P < 0.05) than metronidazole in C. difficile-infected animals. Improved efficacy was not due to an alternative mode of action, as the leads retained the mode of action of metronidazole. Conclusions This study provides the clearest empirical evidence that the high absorption of metronidazole lowers treatment outcomes for CDI and suggests a role for the tetramic acid motif for colon-specific drug delivery. This approach also has the potential to lower systemic toxicity and drug interactions of nitroheterocyclic drugs for treating gastrointestine-specific diseases. PMID:26286574

  13. In vivo bacterial imaging without engineering; A novel probe-based strategy facilitated by endogenous nitroreductase enzymes.

    PubMed

    Stanton, Michael; Cronin, Michelle; Lehouritis, Panos; Tangney, Mark

    2015-01-01

    The feasibility of utilising bacteria as vectors for gene therapy is becoming increasingly recognised. This is primarily due to a number of intrinsic properties of bacteria such as their tumour targeting capabilities, their ability to carry large genetic or protein loads and the availability of well-established genetic engineering tools for a range of common lab strains. However, a number of issues relating to the use of bacteria as vectors for gene therapy need to be addressed in order for the field to progress. Amongst these is the need for the development of non-invasive detection/imaging systems for bacteria within a living host. In vivo optical imaging has advanced preclinical research greatly, and typically involves engineering of bacteria with genetic expression constructs for luminescence (e.g. the lux operon) or fluorescent proteins (GFP etc.). This requirement for genetic modification can be restrictive, where engineering is not experimentally appropriate or technologically feasible (e.g. due to lack of suitable engineering tools). We describe a novel strategy exploiting endogenous bacterial enzymatic activity to specifically activate an exogenously administered fluorescent imaging probe. The red shifted, quenched fluorophore CytoCy5S is reduced to a fluorescent form by bacterial-specific nitroreductase (NTR) enzymes. NTR enzymes are present in a wide range of bacterial genera and absent in mammalian systems, permitting highly specific detection of Gram-negative and Gram-positive bacteria in vivo. In this study, dose-responsive bacterial-specific signals were observed in vitro from all genera examined - E. coli, Salmonella, Listeria, Bifidobacterium and Clostridium difficile. Examination of an NTR-knockout strain validated the enzyme specificity of the probe. In vivo whole-body imaging permitted specific, dose-responsive monitoring of bacteria over time in various infection models, and no toxicity to bacteria or host was observed. This study demonstrates

  14. [Efficacy of tinidazole against anaerobes in comparison with metronidazole, ornidazole, cefoxitin and lamoxactam].

    PubMed

    Werner, H; Kuchenbecker, K; Hammann, R

    1983-06-01

    The in vitro inhibitory activity of tinidazole, metronidazole, ornidazole, cefoxitin and moxalactam was determined against 150 isolates of clinically important anaerobes including Bacteroides fragilis, Bacteroides bivius and Clostridium perfringens by means of agar dilution tests. The members of 18 gramnegative and 14 grampositive species were inhibited by tinidazole at less than or equal to 0,01-8 micrograms/ml thus being without exception susceptible to the drug. A similar in vitro activity was recorded for metronidazole and ornidazole. Though cefoxitin and moxalactam generally had a good in vitro activity against most anaerobic species, single strains of Bacteroides thetaiotaomicron, B. distasonis, Clostridium difficile and Eubacterium rectale were resistant to these drugs. With regard to its in vitro activity, tinidazole seems to be a promising substance for the therapy of anaerobic infections.

  15. [Comparative study, using 3 methods, of the sensitivity to metronidazole and ornidazole of anaerobic or related bacteria].

    PubMed

    Gallusser, A

    1983-01-01

    A comparative study of the sensitivity to metronidazole and ornidazole of 127 anaerobic or microaerophilic strains isolated from various clinical samples showed that the activity of both products was similar: the distribution of sensitive and resistant strains was identical. However, the in vitro activity level of metronidazole was slightly higher. This difference, though statistically significant, had no incidence on therapeutic indications. The determination of sensitivity towards the two nitroimidazoles was carried out by three methods: broth dilution and agar diffusion for metronidazole; and broth dilution and disk-broth for ornidazole. Two of these methods, broth dilution and disk-broth, gave concordant results. Conversely, the limits of the agar diffusion technique were shown to be related to independent biological factors such as bacterial motility and slow growth rate. The poor accuracy of this method limits its use in detecting total resistance.

  16. Non-destructive determination of metronidazole powder by using artificial neural networks on short-wavelength NIR spectroscopy

    NASA Astrophysics Data System (ADS)

    Zhao, Lingzhi; Dou, Ying; Mi, Hong; Ren, Meiyan; Ren, Yulin

    2007-04-01

    The present study aimed at providing a new method in sight into short-wavelength near-infrared (NIR) spectroscopy of in pharmaceutical quantitative analysis. To do that, 124 experimental samples of metronidazole powder were analyzed using artificial neural networks (ANNs) in the 780-1100 nm region of short-wavelength NIR spectra. In this paper, metronidazole was as active component and other two components (magnesium stearate and starch) were as excipients. Different preprocessing spectral data (first-derivative, second-derivative, standard normal variate (SNV) and multiplicative scatter correction (MSC)) were applied to establish the ANNs models of metronidazole powder. The degree of approximation, a new evaluation criterion of the networks was employed to prove the accuracy of the predicted results. The results presented here demonstrate that the short-wavelength NIR region is promising for the fast and reliable determination of major component in pharmaceutical analysis.

  17. Vulvoperineal Crohn's disease responsive to metronidazole*

    PubMed Central

    Rosmaninho, Aristóteles; Sanches, Madalena; Salgado, Marta; Alves, Rosário; Selores, Manuela

    2013-01-01

    Crohn's disease is a multisystem chronic granulomatous inflammatory disease that primarily affects the gastrointestinal tract. In the majority of the cases, the cutaneous manifestations follow the intestinal disease, but occasionally dermatological lesions are the inaugural event and may constitute the only sign of the disease. Vulvoperineal involvement is rare, may precede bowel symptoms by months to years and may go unrecognized. Due to the paucity of reports of Crohn's disease at this location and in the absence of randomized trials, there are no standard treatments for the cutaneous disease. We describe the case of a 47 year-old woman with vulvoperineal Crohn's disease without digestive involvement, that was successfully managed with metronidazole. PMID:24346884

  18. DNA breakage due to metronidazole treatment.

    PubMed

    Menéndez, D; Rojas, E; Herrera, L A; López, M C; Sordo, M; Elizondo, G; Ostrosky-Wegman, P

    2001-07-01

    The mutagenicity of metronidazole [1-(hidroxyethyl)-2-methyl-5-nitroimidazole] (MTZ) has been shown in different prokaryotic systems. However, data on human cells are still contradictory. In this study DNA damage was determined by the single cell gel electrophoresis (SCGE) assay, in lymphocytes from 10 healthy subjects treated with therapeutic doses of this drug. Samples were obtained before treatment, as well as 1 and 15 days after ending treatment. Results showed a significant increase of DNA strand breaks 1 day after ending treatment, although, an inverse correlation between the amount of DNA damage and plasma concentrations of MTZ was obtained. Thus, the observed damage may be induced by some MTZ metabolite rather than by the parent drug. Interestingly, the amount of DNA damage returned to basal levels 15 days after ending treatment, except in two individuals. This persistent damage should be further investigated.

  19. Novel metronidazole-chalcone conjugates with potential to counter drug resistance in Trichomonas vaginalis.

    PubMed

    Anthwal, Amit; Rajesh, U Chinna; Rawat, M S M; Kushwaha, Bhavana; Maikhuri, Jagdamba P; Sharma, Vishnu L; Gupta, Gopal; Rawat, Diwan S

    2014-05-22

    Trichomoniasis is the most prevalent, curable sexually transmitted disease (STD), which increases risk of viral STDs and HIV. However, drug resistance has been developed by some strains of Trichomonas vaginalis against Metronidazole (MTZ), the FDA approved drug against trichomoniasis. In the present study twenty two chalcone hybrids of metronidazole have been synthesized in a quest to get new molecules with higher potential against metronidazole-resistant T. vaginalis. All new hybrid molecules were found active against T. vaginalis with varying levels of activity against MTZ-susceptible and resistant strains. Eight compounds (4a, 4c, 4d, 4e, 4f, 4h, 4q and 4s) were found as active as the standard drug with an MIC of 1.56 μg/ml against MTZ-susceptible strain. However, compounds 4e, 4h and 4m were 4-times more active than MTZ against drug-resistant T. vaginalis, amongst which 4e and 4h were most promising against both susceptible and resistant strains.

  20. Metronidazole as a protector of cells from electromagnetic radiation of extremely high frequencies

    NASA Astrophysics Data System (ADS)

    Kuznetsov, Pavel E.; Malinina, Ulia A.; Popyhova, Era B.; Rogacheva, Svetlana M.; Somov, Alexander U.

    2006-08-01

    It is well known that weak electromagnetic fields of extremely high frequencies cause significant modification of the functional status of biological objects of different levels of organization. The aim of the work was to study the combinatory effect of metronidazole - the drug form of 1-(2'hydroxiethil)-2-methil-5-nitroimidazole - and electromagnetic radiation of extremely high frequencies (52...75 GHz) on the hemolytic stability of erythrocytes and hemotaxis activity of Infusoria Paramecium caudatum.

  1. [In vitro susceptibility of Trichomonas vaginalis to metronidazole, ornidazole and proton pump inhibitors pantoprazole and esomeprazole].

    PubMed

    Aksoy Gökmen, Ayşegül; Girginkardeşler, Nogay; Kilimcioğlu, Ali Ahmet; Şirin, Mümtaz Cem; Özbilgin, Ahmet

    2016-01-01

    The current treatment of trichomoniasis is based on the use of 5-nitroimidazole derivatives. Although metronidazole is reliable, inexpensive and highly effective against anaerobic microorganisms and protozoa, the development of metronidazole-resistant T.vaginalis strains pose to an increasing problem. Nitroimidazoles are compounds having azomycin (2-nitroimidazole) chemical structure and are obtained from Streptomyces strains. Benzimidazole, which is found in the structure of proton pump inhibitors, is also present in the other components that have antiprotozoal activity. In this study, the in vitro susceptibility of T.vaginalis against metronidazole, ornidazole, and the proton pump inhibitors which are tested recently as antiprotozoal agents; pantoprazole and esomeprazole was investigated. For this purpose a clinical T.vaginalis strain which was formerly isolated and stored after cryopreservation process in our laboratory was used. Minimum inhibitory concentration (MIC) and minimum lethal concentration (MLC) values of those agents against to this strain were determined in vitro by dilution method in 24-well cell culture plates. Trypticase yeast extract maltose medium, horse serum and antibiotic (penicillin + streptomycin) were distributed to each well of cell culture plates and after metronidazole, ornidazole, pantoprazole and esomeprazole solutions were added to two wells for each as 800, 400, 200, 100, 50 and 25 µg/ml, followed by the addition of 1 ml 5x10(3) T.vaginalis trophozoites into each well. Plates were incubated at 37°C, and viability and motility of the trophozoites were evaluated under light microscope at 24, 48 and 72 hours after incubation. MIC and MLC values of metronidazole/ornidazole in the 72(th) hour were found as 50 µg/ml and 100 µg/ml, respectively. MIC and MLC values for pantoprazole in the 72th hour were 200 µg/ml and 400 µg/ml, while the values for esomeprazole were 400 µg/ml ve 800 µg/ml, respectively. As a result, T

  2. [Susceptibility of potential periodontopathic bacteria to metronidazole, spiramycin and their combination].

    PubMed

    Mouton, C; Dextraze, L; Mayrand, D

    1984-03-01

    A total of 65 bacterial strains originating mostly from subgingival plaque were tested for their susceptibilities to metronidazole, spiramycin, and their combination, ornidazole, erythromycin and tetracycline by means of an agar dilution technique. All agents were active against all anaerobic Gram-negative rods. Bacteroides gingivalis and Fusobacterium nucleatum showed marked susceptibility to metronidazole (MIC less than or equal to 0.06 microgram/ml) whereas 4-64 micrograms/ml were required to inhibit the capnophilic Actinobacillus actinomycetemcomitans and Capnocytophaga. Gram-positive facultatives were resistant to nitro-imidazoles but were inhibited at macrolide concentrations less than or equal to 0.5 microgram/ml. Except for F. nucleatum and Veillonella strains (2 less than or equal to MIC less than or equal to 128 micrograms/ml) macrolides were active against all other anaerobic bacteria tested. At concentrations less than or equal to 2 micrograms/ml the combination of spiramycin and metronidazole (2 : 1) was active against virtually all bacteria tested but our results failed to show a synergistic effect.

  3. Synthesis of New Nitrofluoroquinolone Derivatives with Novel Anti-Microbial Properties against Metronidazole Resistant H. pylori.

    PubMed

    Abu-Qatouseh, Luay; Abu-Sini, Mohammad; Mayyas, Amal; Al-Hiari, Yusuf; Darwish, Rula; Aburjai, Talal

    2017-01-04

    One of the major therapeutic approaches to preventing relapse and accelerating the healing of duodenal and gastric ulcers is the eradication of Helicobacter pylori. Due to the emergence of antibiotic resistance among clinical strains of H. pylori, alternative approaches using newly discovered antimicrobial agents in combination with the standard regimens for the treatment of H. pylori are increasingly needed. The purpose of the present study was to investigate the effect of newly synthesized 8-nitroflouroqunolone derivatives when used either alone or when combined with metronidazole against metronidazole-resistant H. pylori. Based on the standard antimicrobial susceptibility testing methods and checkerboard titration assay, all of the tested compounds showed interesting antimicrobial activity against 12 clinical strains of H. pylori, with the best in vitro effect for compound 3c. In addition, synergistic and additive activities of some of the tested compounds were observed when combined with metronidazole. Furthermore, among the tested nitroflouroquinolone derivatives, compound 3b showed significant urease inhibition activity with IC50 of 62.5 µg/mL. These results suggest that 8-nitroflouroquinolone derivatives may have a useful role in combination with anti-H. pylori drugs in the management of H. pylori-associated diseases.

  4. Metronidazole Toxicity in Cockayne Syndrome: A Case Series.

    PubMed

    Wilson, Brian T; Strong, Andrew; O'Kelly, Sean; Munkley, Jennifer; Stark, Zornitza

    2015-09-01

    Cockayne syndrome (CS) is a rare genetic disorder characterized by small stature, intellectual disability, and accelerated pathologic aging. Through the Cockayne Syndrome Natural History Study, we have identified 8 cases of acute hepatic failure after metronidazole administration (8% of our cohort), 3 of which were fatal. The interval between initial administration and death was 6 to 11 days. Two of these patients also experienced acute neurologic deficit. Both hepatotoxicity and acute neurologic deficit have been reported previously as extremely rare adverse events after metronidazole administration. However, we have not identified any patients with CS who have received metronidazole without serious adverse effects. We recommend that a diagnosis of CS be considered an absolute contraindication to the use of metronidazole.

  5. Understanding the Broad Substrate Repertoire of Nitroreductase Based on Its Kinetic Mechanism*

    PubMed Central

    Pitsawong, Warintra; Hoben, John P.; Miller, Anne-Frances

    2014-01-01

    The oxygen-insensitive nitroreductase from Enterobacter cloacae (NR) catalyzes two-electron reduction of nitroaromatics to the corresponding nitroso compounds and, subsequently, to hydroxylamine products. NR has an unusually broad substrate repertoire, which may be related to protein dynamics (flexibility) and/or a simple non-selective kinetic mechanism. To investigate the possible role of mechanism in the broad substrate repertoire of NR, the kinetics of oxidation of NR by para-nitrobenzoic acid (p-NBA) were investigated using stopped-flow techniques at 4 °C. The results revealed a hyperbolic dependence on the p-NBA concentration with a limiting rate of 1.90 ± 0.09 s−1, indicating one-step binding before the flavin oxidation step. There is no evidence for a distinct binding step in which specificity might be enforced. The reduction of p-NBA is rate-limiting in steady-state turnover (1.7 ± 0.3 s−1). The pre-steady-state reduction kinetics of NR by NADH indicate that NADH reduces the enzyme with a rate constant of 700 ± 20 s−1 and a dissociation constant of 0.51 ± 0.04 mm. Thus, we demonstrate simple transient kinetics in both the reductive and oxidative half-reactions that help to explain the broad substrate repertoire of NR. Finally, we tested the ability of NR to reduce para-hydroxylaminobenzoic acid, demonstrating that the corresponding amine does not accumulate to significant levels even under anaerobic conditions. Thus E. cloacae NR is not a good candidate for enzymatic production of aromatic amines. PMID:24706760

  6. Bioremediation of 2,4,6-trinitrotoluene by bacterial nitroreductase expressing transgenic aspen.

    PubMed

    Van Dillewijn, Pieter; Couselo, José L; Corredoira, Elena; Delgado, Antonio; Wittich, Rolf-Michael; Ballester, Antonio; Ramos, Juan L

    2008-10-01

    Trees belonging to the genus Populus are often used for phytoremediation due to their deep root formation, fast growth and high transpiration rates. Here, we study the capacity of transgenic hybrid aspen (Populus tremula x tremuloides var. Etropole) which expresses the bacterial nitroreductase gene, pnrA, to tolerate and take-up greater amounts of the toxic and recalcitrant explosive, 2,4,6-trinitrotoluene (TNT) from contaminated waters and soil. Transgenic aspen tolerate up to 57 mg TNT/L in hydroponic media and more than 1000 mg TNT/ kg soil, whereas the parental aspen could not endure in hydroponic culture with more than 11 mg TNT/L or soil with more than 500 mg TNT/kg. Likewise, the phytotoxicological limit for transgenic plants to a constant concentration of TNT was 20 mg TNT/L while wild-type plants only tolerated 10 mg TNT/L. Transgenic plants also showed improved uptake of TNT over wild-type plants when the original TNT concentration was above 35 mg TNT/L in liquid media or 750 mg TNT/kg in soil. Assays with 13C-labeled TNT show rapid adsorption of TNT to the root surface followed by a slower entrance rate into the plant. Most of the 13C-carbon from the labeled TNT taken up bythe plant (> 95%) remains in the root with little translocation to the stem. Altogether, transgenic aspen expressing pnrA are highly interesting for phytoremediation applications on contaminated soil and underground aquifers.

  7. Subjective adverse reactions to metronidazole in patients with amebiasis.

    PubMed

    Ohnishi, Kenji; Sakamoto, Naoya; Kobayashi, Ken-Ichiro; Iwabuchi, Sentaro; Nakamura-Uchiyama, Fukumi; Ajisawa, Atsushi; Yamauchi, Yuko; Takeshita, Nozomi; Yamamoto, Yasuyuki; Tsunoda, Takafumi; Yoshimura, Yukihiro; Tachikawa, Natsuo; Uehira, Tomoko

    2014-10-01

    Subjective adverse reactions to metronidazole were analyzed in 111 patients with amebiasis. Metronidazole was administered to 36 patients at a daily dose of 2250 mg and 75 patients at daily doses lower than 2250 mg. The reactions reported included nausea without vomiting in 11 (9.9%) patients, nausea with vomiting in 2 (1.8%), dysgeusia in 2 (1.8%), diarrhea in 1 (0.9%), headache in 1 (0.9%), numbness in 1 (0.9%), dizziness in 1 (0.9%), urticaria in 1 (0.9%), exanthema in 1 (0.9%), and discomfort in 1 (0.9%). Nausea was reported by 28% (10/36) of the patients receiving metronidazole at a daily dose of 2250 mg and 4% (3/75) of the patients receiving lower daily doses. The duration of the metronidazole administration in days was not associated with the appearance of nausea. No life-threatening adverse reactions were identified, and good clinical therapeutic effects were observed in 96% (107/111) of the patients. While metronidazole appears to be a safe anti-protozoal agent for patients with amebiasis, our results indicate that a daily metronidazole dose of 2250 mg is excessive for amebiasis, as it often induces nausea.

  8. Mutagenicities of 2,4- and 2,6-dinitrotoluenes and their reduced products in Salmonella typhimurium nitroreductase- and O-acetyltransferase-overproducing Ames test strains.

    PubMed

    Sayama, M; Mori, M; Shoji, M; Uda, S; Kakikawa, M; Kondo, T; Kodaira, K I

    1998-12-03

    Mutagenicities of 2,4- and 2,6-dinitrotoluene (2,4-and 2,6-DNT), and reduced metabolites formed by the incubation of 2,4- and 2,6-DNT with Salmonella typhimurium TA98, were tested using S. typhimurium YG strains possessing high level of nitroreductase (NR) and/or O-acetyltransferase (OAT) activities. All compounds tested showed greatest mutagenic activities toward strains YG1041 and YG1042, which possess high levels of NR and OAT activities. The relative mutagenic activities of 2,4-DNT and its related compounds toward YG1041 and YG1042 were aminonitrotoluenes<2,4-DNT<2,2'-dimethyl-5, 5'-dinitroazoxybenzene (2,2'-DM-5, 5'-DNAOB)4-hydroxylamino-2-nitrotoluene (4HA2NT)<4, 4'-dimethyl-3,3'-dinitroazoxybenzene (4,4'-DM-3,3'-DNAOB), and aminonitrotoluenes (2A4AT, 4A2NT)<2,4-DNT<4HA2NT4,4'-dimethyl-3, 3'-dinitroazoxybenzene (4,4'-DM-3,3'-DNAOB)<2HA4NT, respectively. In addition, the relative mutagenic activities of 2,6-DNT and its related compounds toward YG1041 and YG1042 were 2, 6-DNT<2-hydroxylamino-6-nitrotoluene (2HA6NT)<2,2'-dimethyl-3, 3'-dinitroazoxybenzene (2,2'-DM-3,3'-DNAOB), and 2-amino-6-nitrotoluene (2A6NT)<2,6-DNT<2HA6NT, respectively. These results, together with previous findings, suggested that aminohydroxylamino dimethylazoxybenzenes or aminohydroxylamino dimethylazobenzenes produced either by the reduction of hydroxylaminonitrotoluenes or by the reduction of dimethyl dinitroazoxybenzenes are active metabolites responsible for the mutagenic activities of 2,4- and 2,6-DNT.

  9. The restoration of the vaginal microbiota after treatment for bacterial vaginosis with metronidazole or probiotics.

    PubMed

    Ling, Zongxin; Liu, Xia; Chen, Weiguang; Luo, Yueqiu; Yuan, Li; Xia, Yaxian; Nelson, Karen E; Huang, Shaolei; Zhang, Shaoen; Wang, Yuezhu; Yuan, Jieli; Li, Lanjuan; Xiang, Charlie

    2013-04-01

    Whether or not treatment with antibiotics or probiotics for bacterial vaginosis (BV) is associated with a change in the diversity of vaginal microbiota in women was investigated. One hundred fifteen women, consisting of 30 healthy subjects, 30 BV-positive control subjects, 30 subjects with BV treated with a 7-day metronidazole regimen, and 25 subjects with BV treated with a 10-day probiotics regimen, were analyzed to determine the efficacy and disparity of diversity and richness of vaginal microbiota using 454 pyrosequencing. Follow-up visits at days 5 and 30 showed a greater BV cure rate in the probiotics-treated subjects (88.0 and 96 %, respectively) compared to the metronidazole-treated subjects (83.3 and 70 %, respectively [p = 0.625 at day 5 and p = 0.013 at day 30]). Treatment with metronidazole reduced the taxa diversity and eradicated most of the BV-associated phylotypes, while probiotics only suppressed the overgrowth and re-established vaginal homeostasis gradually and steadily. Despite significant interindividual variation, the microbiota of the actively treated groups or participants constituted a unique profile. Along with the decrease in pathogenic bacteria, such as Gardnerella, Atopobium, Prevotella, Megasphaera, Coriobacteriaceae, Lachnospiraceae, Mycoplasma, and Sneathia, a Lactobacillus-dominated vaginal microbiota was recovered. Acting as vaginal sentinels and biomarkers, the relative abundance of Lactobacillus and pathogenic bacteria determined the consistency of the BV clinical and microbiologic cure rates, as well as recurrent BV. Both 7-day intravaginal metronidazole and 10-day intravaginal probiotics have good efficacy against BV, while probiotics maintained normal vaginal microbiota longer due to effective and steady vaginal microbiota restoration, which provide new insights into BV treatment.

  10. [Perioperative metronidazole-prophylaxis for cesarian section (author's transl].

    PubMed

    Gerstner, G; Kofler, E; Huber, J

    1980-12-01

    A prospective, randomized clinical trial was conducted in 103 patients undergoing cesarian section to assess the efficacy of prophylactic, intravenously administered Metronidazole on the infectious morbidity. A group of 53 patients with perioperative Metronidazol-prophylaxis was compared to a similar controll-group without prophylaxis. Bacteriologic swabs were taken from the cervix pre- and postoperatively, using anaerobic transport media. Prophylactic Metronidazole reduced postoperative fever of more than 38 degrees C on two subsequent days from 60% in the controll-group to 30,2% in the Metronidazole-group (p less than 0,01) wound infections were reduced from 18% without to 5,7% with prophylaxis (p less than 0,05) and Endometritis from 30% without to 13,2% with prophylaxis (p less than 0,05). An additional antibiotic therapy was necessary in 44% of the cases in the controllgroup, compared to 24,5% of the cases in the Metronidazolegroup (p less than 0,05). The mean duration of hospitalisation was reduced from 12,1 +/- 3,2 days in the controll-group to 11,2 +/- 2,1 in the Metronidazole-group (p less than 0,01). Anaerobic bacteria were isolated from the servical swabs in 60% preoperatively, with a still increasing incidence to 72% postoperatively, compared to 7% in the Metronidazole-group. Our results suggest, that prophylactic, intravenously administered Metronidazol reduces the infectious morbidity following cesarian section due to the reduction of the anaerobic flora at the female genital-tract.

  11. 2-nitrobenzoate 2-nitroreductase (NbaA) switches its substrate specificity from 2-nitrobenzoic acid to 2,4-dinitrobenzoic acid under oxidizing conditions.

    PubMed

    Kim, Yong-Hak; Song, Woo-Seok; Go, Hayoung; Cha, Chang-Jun; Lee, Cheolju; Yu, Myeong-Hee; Lau, Peter C K; Lee, Kangseok

    2013-01-01

    2-Nitrobenzoate 2-nitroreductase (NbaA) of Pseudomonas fluorescens strain KU-7 is a unique enzyme, transforming 2-nitrobenzoic acid (2-NBA) and 2,4-dinitrobenzoic acid (2,4-DNBA) to the 2-hydroxylamine compounds. Sequence comparison reveals that NbaA contains a conserved cysteine residue at position 141 and two variable regions at amino acids 65 to 74 and 193 to 216. The truncated mutant Δ65-74 exhibited markedly reduced activity toward 2,4-DNBA, but its 2-NBA reduction activity was unaffected; however, both activities were abolished in the Δ193-216 mutant, suggesting that these regions are necessary for the catalysis and specificity of NbaA. NbaA showed different lag times for the reduction of 2-NBA and 2,4-DNBA with NADPH, and the reduction of 2,4-DNBA, but not 2-NBA, failed in the presence of 1 mM dithiothreitol or under anaerobic conditions, indicating oxidative modification of the enzyme for 2,4-DNBA. The enzyme was irreversibly inhibited by 5,5'-dithio-bis-(2-nitrobenzoic acid) and ZnCl(2), which bind to reactive thiol/thiolate groups, and was eventually inactivated during the formation of higher-order oligomers at high pH, high temperature, or in the presence of H(2)O(2). SDS-PAGE and mass spectrometry revealed the formation of intermolecular disulfide bonds by involvement of the two cysteines at positions 141 and 194. Site-directed mutagenesis indicated that the cysteines at positions 39, 103, 141, and 194 played a role in changing the enzyme activity and specificity toward 2-NBA and 2,4-DNBA. This study suggests that oxidative modifications of NbaA are responsible for the differential specificity for the two substrates and further enzyme inactivation through the formation of disulfide bonds under oxidizing conditions.

  12. Identification of intrinsically metronidazole-resistant clades of Gardnerella vaginalis.

    PubMed

    Schuyler, Jessica A; Mordechai, Eli; Adelson, Martin E; Sobel, Jack D; Gygax, Scott E; Hilbert, David W

    2016-01-01

    Gardnerella vaginalis is associated with bacterial vaginosis (BV), the most common cause of vaginal discharge. Metronidazole is a front-line therapy for BV, and treatment failure and recurrent disease are common problems. Whole-genome sequencing studies have revealed that G. vaginalis has a population structure that consists of 4 clades: clades 1 and 3 are associated with BV, whereas clades 2 and 4 are not. To determine if metronidazole susceptibility is associated with population structure, we analyzed 87 clinical isolates and found that metronidazole resistance (MIC ≥32 μg/mL) was highly associated with clade (P<0.0001), as 14/14 clade 3 isolates (100%) and 22/22 clade 4 isolates (100%) exhibited resistance, compared to only 16/37 clade 1 isolates (35%) and 1/14 clade 2 isolates (7.1%). The identification of intrinsically metronidazole-resistant G. vaginalis clades will facilitate future studies on the relationship between metronidazole resistance and BV treatment failure.

  13. Glioblastoma multiforme: treatment by large dose fraction irradiation and metronidazole

    SciTech Connect

    Kapp, D.S.; Wagner, F.C.; Lawrence, R.

    1982-03-01

    In an attempt to overcome the possible radioresistance of glioblastoma multiforme related to the large shoulder on the in vitro survival curves and to sensitize hypoxic tumor cells, a treatment protocol was instituted at Yale University Medical Center and affiliated hospitals, using large dose fraction irradiation therapy in conjunction with the hypoxic cell sensitizer metronidazole. Nineteen patients with biopsy-confirmed, previously untreated, cerebral grade IV glioblastoma multiforme were, following surgery, irradiated once a week at 600 rad per fraction, 3.5 to 4 hours after ingestion of metronidazole, 6 gm/m/sup 2/. A total of 7 treatments were employed, with all patients maintained on antiseizure medications and corticosteroids. Metronidazole levels were determined prior to each treatment and patients were followed closely clinically and with serial computerized tomography (CT) scans. The treatment was well tolerated, in general, with no untoward side effects related to the high dose fraction irradiation. The majority of the patients experienced varying degrees of gastrointestinal upset lasting up to several hours following metronidazole administration. Three patients died of pulmonary emboli. One patient experienced moderately severe ototoxicity. A median survival of 9.4 months was obtained for all 19 patients, suggestive of a prolongation of survival compared to historical controls treated with conventionally fractionated radiation or with unconventional radiation fractionation schemes and metronidazole or misonidazole.

  14. [Metronidazole-resistant trichomoniasis and successful therapy following high dosage].

    PubMed

    Weihe, J; Metelmann, C; Borner, K; Meingassner, J; Orfanos, C E

    1988-04-01

    A patient is reported who suffered for several months from a Trichomonas vaginalis infection that was resistant to the usual low-dose treatment with 5-nitro-imidazole derivatives. Following various ineffective therapeutic trials, the agent was isolated in order to determine its sensitivity to 5-nitro-imidazole. The resistance of the isolate to metronidazole was confirmed in vitro and in an animal experiment; the patient was therefore treated with high daily doses of metronidazole, 3 x 750 mg orally as well as 2 x 100 mg topically for 14 days. Substitution therapy with zinc was administered in order to normalize the patient's relatively low zinc serum levels. These measures finally led to a clinical cure and elimination of the pathogenic agent. This is the first confirmed case of a metronidazole-resistant Trichomonas vaginalis infection reported in the Federal Republic of Germany.

  15. Metronidazole-Induced Bullous Pemphigoid: A Case Report

    PubMed Central

    Moitra, Saibal; Banerjee, Indranil; Sikder, Ayan; Das, Prasanta

    2015-01-01

    Bullous pemphigoid is an autoimmune cutaneous blistering disorder, the exact pathogenesis of which is still not fully elucidated. Drug-induced bullous pemphigoid eruptions are rare but have been reported earlier with the use of frusemide, psoralens, ibuprofen, galantamine hydrobromide, ACE inhibitors like captopril, spironolactone, penicillin, ampicillin, levofloxacin, penicillamine. We hereby report a case of metronidazole induced bullous pemphigoid (BP) in a 52-year-old male patient suffering from liver abscess following 4 days of drug administration. The skin biopsy findings obtained from the patient were consistent with the diagnosis of bullous pemphigoid (BP). Metronidazole was discontinued and symptomatic treatment was offered to the patient. Following withdrawal of metronidazole, the bullae subsided in the next 7-10 days without any significant residual scarring. The causality assessment performed as per the Naranjo algorithm revealed the case to be probable (Naranjo score 7). PMID:26816913

  16. Topical Metronidazole for Odor Control in Pressure Ulcers.

    PubMed

    Lyvers, Elizabeth; Elliott, David P

    2015-09-01

    There are many remedies that have been recommended for the treatment of foul odor associated with pressure ulcers. This article seeks to review the literature surrounding the use of metronidazole as a safe and effective solution to an oftentimes stubborn and frustrating problem. Other tools used to control odor include bleach-based solutions and charcoal dressings. Metronidazole, with its antianaerobic properties, appears to have a useful role in therapy when applied topically to a pressure ulcer. Commercially available products include 0.75% and 1% creams, gels, lotions, and intravenous solutions. Of the 59 cases viewed throughout several publications, 56 reported nearly complete odor resolution in two to seven days when metronidazole was applied to the wound two or three times daily. Virtually no systemic adverse events have been reported in the literature, despite the risk for systemic absorption. A need remains to monitor for toxicities such as nausea, gastrointestinal distress, and neural toxicities from long-term use.

  17. Application of a Microfluidic Reactor for Screening Cancer Prodrug Activation Using Silica-Immobilized Nitrobenzene Nitroreductase

    DTIC Science & Technology

    2006-01-01

    plasmid pCBJS08. The NcoI digestion of pBAD-A released 33 kb from the (His)6 tag, the Xpress epitope, and the enterokinase cleavage site of the vector...HisA (containing the entire (His)6 tag, Xpress epitope, and enterokinase cleavage site of the vector) led to expression of an inactive protein

  18. Sudden death due to metronidazole/ethanol interaction.

    PubMed

    Cina, S J; Russell, R A; Conradi, S E

    1996-12-01

    Metronidazole (Flagyl), a commonly prescribed antimicrobial agent, can produce a reaction similar to that of disulfiram (Antabuse) when administered to patients drinking ethanol. This drug/chemical interaction results in accumulation of acetaldehyde in the blood. Acetaldehyde is hepatotoxic, cardiotoxic, and arrythmogenic; no lethal serum acetaldehyde level has been established. Sudden death has been reported in patients taking disulfiram while using ethanol; no fatalities have been reported due to ethanol/ metronidazole interactions. Described is a case of a 31-year-old woman who died moments after an assault by a male companion, during which he inflicted minor physical trauma to her upper arm. Toxicologic analysis yielded elevated concentrations of serum ethanol (162 mg/d), acetaldehyde (4.6 mg/d), and metronidazole (0.42 mg/L). The cause of death was reported to be cardiac dysrhythmia due to acetaldehyde toxicity due to an ethanol/ metronidazole interaction. Autonomic stress associated with the assault is likely to have contributed to this woman's death. The mechanism of death is examined.

  19. Failure of thiabendazole and metronidazole in the treatment and suppression of guinea worm disease.

    PubMed

    Belcher, D W; Wunapa, F K; Ward, W B

    1975-05-01

    Guinea worm disease is endemic in West Africa. In 1973 a field drug trial was conducted to compare effectiveness, cost, and side-effects of thiabendazole and metronidazole in treating active guinea worm disease and preventing latent worms from emerging. A mass chemotherapy campaign was planned to follow the drug trial. Only 15.5% of the treated patients expelled the worm completely, and in 28.4% of the cases worms continued to appear. Both drugs were equally unsatisfactory in their anti-helminthic effect. Consequently, our efforts to control guinea worm have shifted from chemotherapy to chemical control of cyclops and improvement of rural water supplies.

  20. Comparative susceptibilities of anaerobic bacteria to metronidazole, ornidazole, and SC-28538.

    PubMed

    Goldstein, E J; Sutter, V L; Finegold, S M

    1978-10-01

    The susceptibilities of 284 anaerobic bacteria, including 55 strains of the Bacteroides fragilis group, were determined by an agar dilution technique to metronidazole and two newer nitroimidazoles, ornidazole and SC-28538. All three agents showed marked in vitro activity against virtually all anaerobic bacteria tested. At concentrations active than either metronidazole or ornidazole. At concentrations of >1 mug/ml, the activities of all three agents were comparable. Propionibacterium and Actinomyces showed significant resistance to all three agents. Anaerobic and microaerophilic members of the genus Streptococcus were also often resistant, in contrast to Peptococcus and Peptostreptococcus strains. In addition, the bactericidal activities of ornidazole and SC-28538 were determined against 27 strains of the B. fragilis group by a broth dilution technique. The minimal inhibitory and minimal bactericidal concentrations of each agent were very close. At concentrations of activity; at concentrations of >/=2 mug/ml, the activies of both agents were similar.

  1. Effects of metronidazole analogues on Giardia lamblia: experimental infection and cell organization.

    PubMed

    Busatti, Haendel G N O; Alves, Ricardo J; Santana-Anjos, Karla G; Gil, Frederico F; Cury, Marcia C; Vannier-Santos, Marcos A; Gomes, Maria A

    2013-02-01

    The chemotherapeutic agents used for the treatment of giardiasis are often associated with adverse side effects and are refractory cases, due to the development of resistant parasites. Therefore the search for new drugs is required. We have previously reported the giardicidal effects of metronidazole (MTZ) and its analogues (MTZ-Ms, MTZ-Br, MTZ-N(3), and MTZ-I) on the trophozoites of Giardia lamblia. Now we evaluated the activity of some giardicidal MTZ analogues in experimental infections in gerbils and its effects on the morphology and ultrastructural organization of Giardia. The giardicidal activity in experimental infections showed ED(50) values significantly lower for MTZ-I and MTZ-Br when compared to MTZ. Transmission electron microscopy was employed to approach the mechanism(s) of action of MTZ analogues upon the protozoan. MTZ analogues were more active than MTZ in changing significantly the morphology and ultrastructure of the parasite. The analogues affected parasite cell vesicle trafficking, autophagy, and triggered differentiation into cysts. These results coupled with the excellent giardicidal activity and lower toxicity demonstrate that these nitroimidazole derivates may be important therapeutic alternatives for combating giardiasis. In addition, our results suggest a therapeutic advantage in obtaining synthetic metronidazole analogues for screening of activities against other infectious agents.

  2. Effects of azithromycin, metronidazole, amoxicillin, and metronidazole plus amoxicillin on an in vitro polymicrobial subgingival biofilm model.

    PubMed

    Soares, Geisla M S; Teles, Flavia; Starr, Jacqueline R; Feres, Magda; Patel, Michele; Martin, Lynn; Teles, Ricardo

    2015-05-01

    Chronic periodontitis is one of the most prevalent human diseases and is caused by dysbiosis of the subgingival microbiota. Treatment involves primarily mechanical disruption of subgingival biofilms and, in certain cases, adjunctive use of systemic antibiotic therapy. In vitro biofilm models have been developed to study antimicrobial agents targeting subgingival species. However, these models accommodate a limited number of taxa, lack reproducibility, and have low throughput. We aimed to develop an in vitro multispecies biofilm model that mimics subgingival plaque, to test antimicrobial agents. Biofilms were cultivated using the Calgary Biofilm Device and were exposed to amoxicillin (AMX), metronidazole (MTZ), azithromycin (AZM), and AMX-MTZ at four different concentrations for 12, 24, or 36 h. Chlorhexidine (CHX) (0.12%) was used as the positive control. The compositions of the biofilms were analyzed by checkerboard DNA-DNA hybridization, and the percent reduction in biofilm metabolic activity was determined using 2,3,5-triphenyltetrazolium chloride and spectrophotometry. Thirty-five of the 40 species used in the inoculum were consistently recovered from the resulting in vitro biofilms. After 36 h of exposure at the 1:27 dilution, AMX-MTZ reduced metabolic activity 11% less than CHX (q = 0.0207) but 54% more than AMX (q = 0.0031), 72% more than MTZ (q = 0.0031), and 67% more than AZM (q = 0.0008). Preliminary evidence of a synergistic interaction between AMX and MTZ was also observed. In summary, we developed reproducible biofilms with 35 subgingival bacterial species, and our results suggested that the combination of AMX and MTZ had greater antimicrobial effects on these in vitro multispecies biofilms than expected on the basis of the independent effects of the drugs.

  3. Effects of Azithromycin, Metronidazole, Amoxicillin, and Metronidazole plus Amoxicillin on an In Vitro Polymicrobial Subgingival Biofilm Model

    PubMed Central

    Teles, Flavia; Starr, Jacqueline R.; Feres, Magda; Patel, Michele; Martin, Lynn

    2015-01-01

    Chronic periodontitis is one of the most prevalent human diseases and is caused by dysbiosis of the subgingival microbiota. Treatment involves primarily mechanical disruption of subgingival biofilms and, in certain cases, adjunctive use of systemic antibiotic therapy. In vitro biofilm models have been developed to study antimicrobial agents targeting subgingival species. However, these models accommodate a limited number of taxa, lack reproducibility, and have low throughput. We aimed to develop an in vitro multispecies biofilm model that mimics subgingival plaque, to test antimicrobial agents. Biofilms were cultivated using the Calgary Biofilm Device and were exposed to amoxicillin (AMX), metronidazole (MTZ), azithromycin (AZM), and AMX-MTZ at four different concentrations for 12, 24, or 36 h. Chlorhexidine (CHX) (0.12%) was used as the positive control. The compositions of the biofilms were analyzed by checkerboard DNA-DNA hybridization, and the percent reduction in biofilm metabolic activity was determined using 2,3,5-triphenyltetrazolium chloride and spectrophotometry. Thirty-five of the 40 species used in the inoculum were consistently recovered from the resulting in vitro biofilms. After 36 h of exposure at the 1:27 dilution, AMX-MTZ reduced metabolic activity 11% less than CHX (q = 0.0207) but 54% more than AMX (q = 0.0031), 72% more than MTZ (q = 0.0031), and 67% more than AZM (q = 0.0008). Preliminary evidence of a synergistic interaction between AMX and MTZ was also observed. In summary, we developed reproducible biofilms with 35 subgingival bacterial species, and our results suggested that the combination of AMX and MTZ had greater antimicrobial effects on these in vitro multispecies biofilms than expected on the basis of the independent effects of the drugs. PMID:25733510

  4. A comparison of the efficacy of metronidazole vaginal gel and Myrtus (Myrtus communis) extract combination and metronidazole vaginal gel alone in the treatment of recurrent bacterial vaginosis

    PubMed Central

    Masoudi, Mansoureh; Rafieian Kopaei, Mahmoud; Miraj, Sepideh

    2017-01-01

    Objective: Due to the high incidence of bacterial vaginosis (BV) and its resistance to chemical medications and considering the anti-bacterial and anti-fungal effects of Myrtus communis, the present study aimed to compare the therapeutic effects of the vaginal gel of M. communis 2% (in metronidazole base) with metronidazole vaginal gel 0.75% alone on BV. Materials and Methods: This research was a randomized controlled clinical trial conducted on 80 women of 18-40 years old with BV. Patients were divided into two groups of 40 women. Diagnostic criteria were Amsel's criteria and Gram staining. The first group received vaginal gel of metronidazole plus M. communis 2% and the second group received metronidazole vaginal gel alone for five consecutive nights. Therapeutic effects and Amsel’s criteria were assessed after one week. Finally, the data were analyzed by SPSS 16 using t-test and Chi square tests. Results: There was a significant difference in the therapeutic response between the two groups. The results demonstrated that the combination of metronidazole and M. communis had a higher efficiency (p<0.05). The patients receiving M. communis in metronidazole gel base did not experience any recurrent BV, but 30% of patients taking metronidazole alone faced recurrent BV after three weeks of follow up. Conclusion: Findings of the study suggested that adding M. communis extract to metronidazole increases the efficiency of BV treatment. PMID:28348968

  5. Norfloxacin and metronidazole topical formulations for effective treatment of bacterial infections and burn wounds

    PubMed Central

    Dua, Kamal; Malipeddi, Venkata Ramana; Madan, Jyotsna; Gupta, Gaurav; Chakravarthi, Srikumar; Awasthi, Rajendra; Kikuchi, Irene Satiko; De Jesus Andreoli Pinto, Terezinha

    2016-01-01

    Introduction Our various previous findings have shown the suitability of norfloxacin in the treatment of bacterial infections and burn wounds in alone as well as in combination with Curcuma longa in various topical (ointments, gels, and creams) and transdermal drug delivery systems. Aims and methods Keeping these facts in consideration, we have made an another attempt to prepare semisolid formulations containing 1% w/w of norfloxacin and metronidazole with different bases like Carbopol, polyethylene glycol, and hydroxypropylmethyl cellulose for effective treatment of bacterial infections and burn wounds. The prepared formulations were evaluated for physicochemical parameters, in vitro drug release, antimicrobial activity, and burn wound healing properties. Results The prepared formulations were compared with Silver Sulfadiazine cream 1%, USP. Antimicrobial activity of norfloxacin semisolid formulations was found to be equally effective against both aerobic and anaerobic bacteria in comparison to a marketed formulation of Silver Sulfadiazine 1% cream, USP. Based on the burn wound healing property, the prepared norfloxacin semisolid formulation was found to be in good agreement with marketed Silver Sulfadiazine 1% cream, USP. Conclusions These findings suggest formulations containing norfloxacin and metronidazole may also prove as an effective alternative for existing remedies in the treatment of bacterial infections and burn wounds. PMID:28386462

  6. Metabolic differences between metronidazole resistant and susceptible strains of Tritrichomonas foetus.

    PubMed

    Cerkasovová, A; Cerkasov, J; Kulda, J

    1984-04-01

    Tritrichomonas foetus mutants resistant to metronidazole lack the hydrogenosomal enzymes pyruvate: ferredoxin oxidoreductase and hydrogenase. Hydrogenosomes of these organisms did not oxidize pyruvate or produce ATP in its presence. Elimination of hydrogenosomal metabolism of pyruvate was compensated by an increased rate of glycolysis. The resistant mutants excreted no organic acids and H2 as metabolic end products. Glycolysis of the resistant T. foetus KV1-1MR-100 can be summarized as 1 mol glucose----2 mol ethanol + 2 mol CO2. The parent strain KV1, excreting H2, CO2 and acidic end products, converted about 10% of glucose to ethanol. Both strains produced ethanol from pyruvate through the action of two cytoplasmic enzymes: pyruvate decarboxylase and alcohol dehydrogenase. The specific activity of the former enzyme, catalyzing nonoxidative decarboxylation of pyruvate to acetaldehyde, was nearly seven times higher in the resistant than in the parent strain. Alcohol dehydrogenase reducing acetaldehyde to ethanol was specific to NADPH; it catalyzed the reverse reaction only slowly, and displayed similar activities in both resistant and sensitive trichomonads. Development of anaerobic metronidazole resistance in T. foetus depended on the loss of pyruvate:ferredoxin oxidoreductase as well as on the ability to increase alcoholic fermentation.

  7. Crystal growth by solvent evaporation and characterization of metronidazole

    NASA Astrophysics Data System (ADS)

    Ramukutty, S.; Ramachandran, E.

    2012-07-01

    Single crystals of metronidazole were crystallized by the slow solvent evaporation method and used as seeds to grow bulk crystals of size 8.0×6.5×2.0 mm3 using top-seeded submerged solution growth. The crystals were characterized using single crystal X-ray diffraction. Fourier transform infrared spectral analysis was made for the absorption bands of various functional groups present in the crystal. UV-vis absorption spectrum was used to identify the presence of nitroimidazole in metronidazole. Morphology study revealed that the growth is prominent along the c-axis and the prominent face is {010}. Thermal stability and thermal decomposition were analyzed using thermo calorimetry.

  8. Biowaiver monographs for immediate release solid oral dosage forms: metronidazole.

    PubMed

    Rediguieri, Camila F; Porta, Valentina; G Nunes, Diana S; Nunes, Taina M; Junginger, Hans E; Kopp, Sabine; Midha, Kamal K; Shah, Vinod P; Stavchansky, Salomon; Dressman, Jennifer B; Barends, Dirk M

    2011-05-01

    Literature data relevant to the decision to allow a waiver of in vivo bioequivalence (BE) testing for the approval of immediate release (IR) solid oral dosage forms containing metronidazole are reviewed. Metronidazole can be assigned to Biopharmaceutics Classification System Class I. Most BE studies that were identified reported the investigated formulations to be bioequivalent, indicating the risk of bioinequivalence to be low. Formulations showing differences in bioavailability showed dissimilarities in in vitro dissolution profiles. Furthermore, metronidazole has a wide therapeutic index. It is concluded that a biowaiver for solid IR formulations is justified, provided: (a) the test product and its comparator are both rapidly dissolving; (b) meet similarity of the dissolution profiles at pH 1.2, 4.5, and 6.8; (c) the test product contains only excipients present in IR drug products approved in International Conference on Harmonisation (ICH) or associated countries in the same dosage form; and (d) if the test product contains sorbitol, sodium laurilsulfate, or propylene glycol, the test product needs to be qualitatively and quantitatively identical to its comparator with respect to these excipients [corrected]..

  9. [Convulsive seizures and polyneuritis in a patient with lupus treated with metronidazole (author's transl)].

    PubMed

    Herreman, G; Krainik, F; Betous, F; Nicolas, M O; Mundler, B

    1981-01-01

    A 20-year-old patient with biologically-confirmed lupus developed a perirenal abscess following puncture biopsy of the kidney. Postoperative treatment included metronidazole at a mean dose of 2.5 g daily for 68 days (total dose : 165 g). Generalised convulsive seizures occurred on four occasions, associated with paresthesia of the four limbs, but without loss of motor or reflex activity, though some distal hypoesthesia was detected. An acute lupus attack was eliminated, the convulsive seizures not recurring after discontinuation of treatment, and the paresthesias diminishing progressively over a period of three months. Electrical investigations showed lack of motor anomalies but a marked reduction in sensory conduction. This is the 13th reported case of polyneuritis due to metronidazole, the 4th case of convulsive seizures, and the first case in which both manifestations occurred. The plasma concentration curve after oral administration of 1 g of the product to this patient demonstrated that the product was not being metabolised in a pathological manner.

  10. Draft Genome Sequence of a Metronidazole-Resistant Gardnerella vaginalis Isolate

    PubMed Central

    Schuyler, Jessica A.; Chadwick, Sean G.; Mordechai, Eli; Adelson, Martin E.; Gygax, Scott E.

    2015-01-01

    We report the draft genome sequence of a Gardnerella vaginalis strain (3549624) isolated from a vaginal specimen. G. vaginalis is associated with bacterial vaginosis, the most common cause of vaginal discharge, which is often treated with metronidazole. This isolate is highly resistant to metronidazole (MIC, 500 µg/ml) and may be useful for comparative genomic studies to determine the molecular basis of metronidazole resistance in this species. PMID:26337887

  11. Furazolidone- and Nitrofurantoin-Resistant Helicobacter pylori: Prevalence and Role of Genes Involved in Metronidazole Resistance

    PubMed Central

    Kwon, Dong H.; Lee, Miae; Kim, J. J.; Kim, J. G.; El-Zaatari, F. A. K.; Osato, M. S.; Graham, D. Y.

    2001-01-01

    The prevalence of furazolidone, nitrofurantoin, and metronidazole resistance among Helicobacter pylori strains was assessed with 431 clinical isolates. Fifty-two percent were metronidazole resistant, compared to 2% (7 of 431) with resistance to furazolidone and nitrofurantoin. All seven furazolidone- and nitrofurantoin-resistant isolates were also metronidazole resistant. rdxA, frxA, and fdxB knockouts did not result in furazolidone or nitrofurantoin resistance. These data suggest that furazolidone and nitrofurantoin may be good alternatives to metronidazole for treating H. pylori infection. PMID:11120984

  12. High-dose vaginal maintenance metronidazole for recurrent bacterial vaginosis: a pilot study.

    PubMed

    Aguin, Tina; Akins, Robert A; Sobel, Jack D

    2014-05-01

    The purpose of this study was to explore the benefit of high-dose intravaginal metronidazole as a maintenance therapy in reducing recurrence rates of bacterial vaginosis (BV). Eighteen women with a history of recurrent BV and symptomatic BV were treated with metronidazole 750 mg suppository intravaginally daily for 7 days. Those in remission by Amsel criteria received metronidazole 750 mg twice weekly for 3 months with further follow-up for 3 months. High-dose metronidazole intravaginally was associated with rare clinical recurrence during the period of use. After cessation of suppression therapy, recurrence was high.

  13. Cloning of Bacteroides fragilis plasmid genes affecting metronidazole resistance and ultraviolet survival in Escherichia coli

    SciTech Connect

    Wehnert, G.U.; Abratt, V.R.; Goodman, H.J.; Woods, D.R. )

    1990-03-01

    Since reduced metronidazole causes DNA damage, resistance to metronidazole was used as a selection method for the cloning of Bacteroides fragilis genes affecting DNA repair mechanisms in Escherichia coli. Genes from B. fragilis Bf-2 were cloned on a recombinant plasmid pMT100 which made E. coli AB1157 and uvrA, B, and C mutant strains more resistant to metronidazole, but more sensitive to far uv irradiation under aerobic conditions. The loci affecting metronidazole resistance and uv sensitivity were linked and located on a 5-kb DNA fragment which originated from the small 6-kb cryptic plasmid pBFC1 present in B. fragilis Bf-2 cells.

  14. Differential expression and immunolocalization of antioxidant enzymes in Entamoeba histolytica isolates during metronidazole stress.

    PubMed

    Iyer, Lakshmi Rani; Singh, Nishant; Verma, Anil Kumar; Paul, Jaishree

    2014-01-01

    Entamoeba histolytica infections are endemic in the Indian subcontinent. Five to eight percent of urban population residing under poor sanitary conditions suffers from Entamoeba infections. Metronidazole is the most widely prescribed drug used for amoebiasis. In order to understand the impact of metronidazole stress on the parasite, we evaluated the expression of two antioxidant enzymes, peroxiredoxin and FeSOD, in Entamoeba histolytica isolates during metronidazole stress. The results reveal that, under metronidazole stress, the mRNA expression levels of these enzymes did not undergo any significant change. Interestingly, immunolocalization studies with antibodies targeting peroxiredoxin indicate differential localization of the protein in the cell during metronidazole stress. In normal conditions, all the Entamoeba isolates exhibit presence of peroxiredoxin in the nucleus as well as in the membrane; however with metronidazole stress the protein localized mostly to the membrane. The change in the localization pattern was more pronounced when the cells were subjected to short term metronidazole stress compared to cells adapted to metronidazole. The protein localization to the cell membrane could be the stress response mechanism in these isolates. Colocalization pattern of peroxiredoxin with CaBp1, a cytosolic protein, revealed that the membrane and nuclear localization was specific to peroxiredoxin during metronidazole stress.

  15. Universal high-level primary metronidazole resistance in Helicobacter pylori isolated from children in Egypt.

    PubMed

    Sherif, May; Mohran, Zaynab; Fathy, Hanan; Rockabrand, David M; Rozmajzl, Patrick J; Frenck, Robert W

    2004-10-01

    Antimicrobial susceptibility testing was performed on 48 isolates of Helicobacter pylori recovered from Egyptian children undergoing routine endoscopies. The isolates were universally highly resistant to metronidazole, but resistance to other tested antimicrobial agents was rare (4% for clarithromycin, erythromycin, and azithromycin resistance versus 2% for ciprofloxacin and ampicillin resistance). Use of metronidazole for the treatment of H. pylori in Egypt should be avoided.

  16. [Metronidazole-Induced Encephalopathy during Brain Abscess Treatment:Two Case Reports].

    PubMed

    Yokoyama, Yuka; Asaoka, Katsuyuki; Sugiyama, Taku; Uchida, Kazuki; Shimbo, Daisuke; Kobayashi, Satoshi; Itamoto, Koji

    2015-10-01

    Metronidazole is a widely used antibiotic against anaerobic bacteria and protozoa. We report two cases of metronidazole-induced encephalopathy(MIE)during treatment of a brain abscess with metronidazole. The patients developed mental disturbance, and brain MRI showed reversible signals on DWI, FLAIR, and T2. Case 1: A 48-year-old woman was admitted to our hospital with a cerebellar abscess. We initiated treatment with oral metronidazole. After taking the medication, she developed mental disturbance, and her brain MRI showed a hyperintensity within the corpus callosum. We suspected metronidazole toxicity and discontinued metronidazole treatment. The symptoms resolved rapidly within a week, and the hyperintensity on the MRI disappeared. Case 2: A 22-year-old man was admitted to our hospital with a brain abscess. We initiated treatment with oral metronidazole. On day 38, he developed mental disturbance, and his MRI showed hyperintensities within the bilateral dentate nuclei and corpus callosum. These symptoms were consistent with MIE. After cessation of metronidazole, his symptoms and abnormal MRI signals completely disappeared.

  17. Comparison between the efficacy of metronidazole vaginal gel and Berberis vulgaris (Berberis vulgaris) combined with metronidazole gel alone in the treatment of bacterial vaginosis

    PubMed Central

    Masoudi, Mansoure; Kopaei, Mahmoud Rafieian; Miraj, Sepideh

    2016-01-01

    Background Bacterial vaginosis is one of the most prevalent complications among reproductive-aged women. Antibacterial and antifungal effects of Berberis vulgaris have been demonstrated in vitro and in vivo. Objectives This study aimed to compare the therapeutic effects of the vaginal gel of Berberis vulgaris 5% (in metronidazole base) with metronidazole vaginal gel 0.75% on bacterial vaginosis on 80 patients referred to the Hajar Hospital from January 2012 to April 2013. Methods This study was a randomized clinical trial research on 80 women affected by bacterial vaginosis, who were randomly divided into two groups of 40 participants. Diagnostic criteria were Amsel’s criteria and Gram stain. Berberis vulgaris 5% (in metronidazole gel base) or metronidazole vaginal gel for five-night usage was prescribed to each group, and after two to seven days therapeutic effects and Amsel criteria were assessed. Data analysis was performed by SPSS 16 using Student t-test, chi-square, and ANOVA tests. Results Findings of the study showed a statistically significant difference with regard to treatment response between the study groups (p<0.001), and the Berberis vulgaris group had a better response than the metronidazole gel group. The patients in groups of Berberis vulgaris in a metronidazole gel base did not experience any relapse, but, in the metronidazole group, 30% of patients experienced relapse during three weeks’ follow-up. Conclusions Findings of the study showed that adding Berberis vulgaris fruit extract on metronidazole improve the efficacy of bacterial vaginosis therapy. Clinical trial registration The trial was registered at the Iranian Registry of Clinical Trials (http://www.irct.ir) with the IRCT ID: IRCT201411102085N13. Funding Shahrekord University of Medical Sciences supported this research. PMID:27757195

  18. D-allose and D-psicose reinforce the action of metronidazole on trichomonad.

    PubMed

    Harada, Masakazu; Kondo, Emi; Hayashi, Hiromi; Suezawa, Chigusa; Suguri, Setsuo; Arai, Meiji

    2012-04-01

    The effects of D-allose and D-psicose on Tritrichomonas foetus were examined. They were cultured in F-bouillon medium including glucose, but had never increased when glucose was substituted to those sugars. When cultured in a medium including a dose of ED(50) metronidazole and those sugars, trichomonad density was significantly less than that in a medium with metronidazole only. D-Allose remarkably reinforced the action of metronidazole. This means there are some interactions between metronidazole and those sugars. Although the mechanism is not clear, by using those sugars for treatment with metronidazole, the drug dosage could be lowered and the development of drug resistance of trichomonad parasites might be prevented.

  19. A novel metronidazole fluorescent nanosensor based on graphene quantum dots embedded silica molecularly imprinted polymer.

    PubMed

    Mehrzad-Samarin, Mina; Faridbod, Farnoush; Dezfuli, Amin Shiralizadeh; Ganjali, Mohammad Reza

    2017-06-15

    A novel optical nanosensor for detection of Metronidazole in biological samples was reported. Graphene quantum dots embedded silica molecular imprinted polymer (GQDs-embedded SMIP) was synthesized and used as a selective fluorescent probe for Metronidazole detection. The new synthesized GQDs-embedded SMIP showed strong fluorescent emission at 450nm excited at 365nm which quenched in presence of Metronidazole as a template molecule.. The quenching was proportional to the concentration of Metronidazole in a linear range of at least 0.2μM to 15μM. The limit of detection for metronidazole determination was obtained 0.15μM. The nanosensor successfully worked in plasma matrixes.

  20. Clindamycin vaginal cream vs oral metronidazole in the treatment of bacterial vaginosis.

    PubMed

    Arredondo, J L; Higuera, F; Hidalgo, H; Narcio, L; Casanova, G; Beltran, M; Sanchez, C J

    1992-01-01

    This study was designed to compare the safety/efficacy of the treatment of 2% clindamycin vaginal cream and oral metronidazole in 184 women with bacterial vaginosis. This was a randomized, prospective, multicenter, double-blind, controlled study. Patients were randomized to either Clindamycin phosphate vaginal cream 2%, 5 gm intravaginally at bedtime, and placebo oral metronidazole capsules taken twice daily, or oral metronidazole capsules, 500 mg, taken twice daily, and placebo clindamycin vaginal cream, 5 gm to be administered intravaginally at bedtime. All treatments were for 7 days. Patients were seen for followup at 4-13 days and 20-43 days after completion of protocol therapy. 2 investigators in Mexico City enrolled a total of 184 patients (91 clindamycin and 93 metronidazole). 1 patient never received drugs after enrollment, leaving 183 valuable for safety. A total of 114 were valuable for efficacy. Protocol regimens were comparable in efficacy (p=0.22) and the percentage of cure/improvement was 87% in the clindamycin group compared to 79% in the metronidazole group. No relapse was observed in the clindamycin group, as opposed to 7% in the metronidazole group. The clindamycin group had a failure of 13% while this was 15% in the metronidazole group. Both treatments were well-tolerated. Most of the events were either vulvovaginal irritation upon application of the study drug, or the development of vaginitis/cervicitis. The 1 event classified as serious in this study (metronidazole group) was generalized rash which, in the opinion of the investigator, was related to the study drug. There were 4 nongenital tract side effects (1 gastrointestinal, 2 dermatologic, and 1 allergy) all in the metronidazole group. The authors can conclude that clindamycin 2% vaginal cream is at least as effective as orally administered metronidazole for the treatment of bacterial vaginosis in nonpregnant women.

  1. FG90 chitosan as a new polymer for metronidazole mucoadhesive tablets for vaginal administration.

    PubMed

    Perioli, Luana; Ambrogi, Valeria; Pagano, Cinzia; Scuota, Stefania; Rossi, Carlo

    2009-07-30

    Topical administration of the antibacterial metronidazole (MET) represents the most common therapy in the treatment of bacterial vaginosis (BV). The formulations generally available for BV therapy are creams, gels, vaginal lavages and vaginal suppositories. In this study, a new dosage form, containing MET, was developed with the aim to realize vaginal mucoadhesive tablets by including bioadhesive polymers as chitosan (FG90C), polyvinylpyrrolidone (PVPK90) and polycarbophil (PCPAA1), blended in different ratios. All formulations were characterized by studies of DSC, friability, hardness, hydration, mucoadhesion, in vitro release and antibacterial activity. All polymer mixtures employed were used to prepare tablets with the compactness and hardness so as allow the application on vaginal mucosa. FG90C performances improved in particular when mixed to PVPK90 (1:1 ratio). This kind of delivery system is suitable for formulating MET for topical application representing a good alternative to traditional dosage forms for vaginal topical administration.

  2. Tribulus terrestris ameliorates metronidazole-induced spermatogenic inhibition and testicular oxidative stress in the laboratory mouse

    PubMed Central

    Kumari, Mrinalini; Singh, Poonam

    2015-01-01

    Objective: The present study was undertaken to evaluate the protective effects of the fruit extract of Tribulus terrestris (TT) on the metronidazole (MTZ)-induced alterations in spermatogenesis, sperm count, testicular functions, and oxidative stress. Materials and Methods: Thirty adult Swiss strain mice were divided into six groups. Animals of Groups I and II served as untreated and vehicle-treated controls, while that of Groups III and IV were administered with MTZ (500 mg/kg BW/day) and TT (200 mg/kg BW/day) alone for 28 days, respectively. Low (100 mg/kg BW/day) and high (200 mg/kg BW/day) doses of TT along with MTZ (500 mg/kg BW/day) were administered for 28 days in the mice of Groups V and VI, respectively. Twenty four hours after the last treatment, all the animals were euthanized to study the histological changes in the testis and sperm count in the epididymis. Testicular functional markers, lipid peroxidation (LPO) and the activities of antioxidant enzymes, e.g., superoxide dismutase, catalase, glutathione peroxidase, and glutathione reductase, were also assessed in the mice of all the groups. Results: Metronidazole caused marked alterations in the testicular weight, spermatogenesis, activities of antioxidant enzymes, lactate dehydrogenase, alkaline phosphatase, and the level of LPO. The epididymal sperm count also declined significantly in MTZ-treated group. These changes were partially restored following co-administration of 500 mg/kg BW/day of MTZ and 100 mg/kg BW/day of TT. However, in the mice co-administered with 500 mg/kg BW/day of MTZ and 200 mg/kg BW/day of TT, the changes reverted back completely, similar to that of the controls. Conclusion: The fruit extract of TT ameliorates the MTZ-induced alterations in the testis. PMID:26069369

  3. Molecular analysis of the carbapenem and metronidazole resistance mechanisms of Bacteroides strains reported in a Europe-wide antibiotic resistance survey.

    PubMed

    Sóki, József; Eitel, Zsuzsa; Urbán, Edit; Nagy, Elisabeth

    2013-02-01

    Here we examine the carbapenem and metronidazole resistance mechanisms of 640 Bacteroides strains reported in the 2008-2009 European antibiotic susceptibility survey. Of the 22 strains with elevated imipenem minimum inhibitory concentrations (≥4 μg/mL), 10 were cfiA-positive and out of these 5 carried activating insertion sequence (IS) elements in the upstream regions of the cfiA genes. However, resistant strains with cfiA genes but with no activating IS elements were found (n=2) as well as a resistant strain with no cfiA gene. In the former the resistance phenotypes by Etest were heterogeneous, whilst in the latter no carbapenemase production was seen; both mechanisms have been rarely observed, examined and characterised. Interestingly, few (n=3) nim-positive strains were found, including one metronidazole-resistant strain harbouring nimE activated by ISBf6, and two susceptible strains harbouring chromosomally located nim genes.

  4. Helicobacter pylori infection treated with a tripotassium dicitrato bismuthate and metronidazole combination.

    PubMed

    Weil, J; Bell, G D; Powell, K; Morden, A; Harrison, G; Gant, P W; Jones, P H; Trowell, J E

    1990-12-01

    Seventy-two patients with H. pylori infection in their antral mucosa took part in the study. Forty-three received metronidazole 400 mg t.d.s. for two weeks, plus De-Nol tabs 2 b.d. for four weeks, and the remaining 29 patients received metronidazole 400 mg t.d.s. for two weeks plus De-Nol liquid 5 ml q.d.s. for four weeks. Seven of 57 H. pylori isolates were found to have pre-treatment metronidazole resistance. Success, in terms of eradication of H. pylori, was assessed using a one-month post-treatment 14C urea breath test. Successful eradication of H. pylori was achieved in 72% and 79%, respectively, of the metronidazole/De-Nol tablet and metronidazole/De-Nol liquid groups. These figures increased to 87% and 84%, respectively, if the patients whose organisms were known to be metronidazole-sensitive were considered in isolation. H. pylori was successfully eradicated in only one of seven patients with a metronidazole-resistant organism.

  5. Subinhibitory concentrations of metronidazole increase biofilm formation in Clostridium difficile strains.

    PubMed

    Vuotto, Claudia; Moura, Ines; Barbanti, Fabrizio; Donelli, Gianfranco; Spigaglia, Patrizia

    2016-03-01

    Resistance mechanism to metronidazole is still poorly understood, even if the number of reports on Clostridium difficile strains with reduced susceptibility to this antibiotic is increasing. In this study, we investigated the ability of the C. difficile strains 7032994, 7032985 and 7032989, showing different susceptibility profiles to metronidazole but all belonging to the PCR ribotype 010, to form biofilm in vitro in presence and absence of subinhibitory concentrations of metronidazole. The quantitative biofilm production assay performed in presence of metronidazole revealed a significant increase in biofilm formation in both the susceptible strain 7032994 and the strain 7032985 exhibiting a reduced susceptibility to this antibiotic, while antibiotic pressure did not affect the biofilm-forming ability of the stable-resistant strain 7032989. Moreover, confocal microscopy analysis showed an abundant biofilm matrix production by the strains 7032994 and 7032885, when grown in presence of metronidazole, but not in the stable-resistant one. These results seem to demonstrate that subinhibitory concentrations of metronidazole are able to enhance the in vitro biofilm production of the above-mentioned PCR ribotype 010 C. difficile strains, susceptible or with reduced susceptibility to this antibiotic, suggesting a possible role of biofilm formation in the multifactorial mechanism of metronidazole resistance developed by C. difficile.

  6. Search for novel candidate mutations for metronidazole resistance in Helicobacter pylori using next-generation sequencing.

    PubMed

    Binh, Tran Thanh; Suzuki, Rumiko; Trang, Tran Thi Huyen; Kwon, Dong Hyeon; Yamaoka, Yoshio

    2015-04-01

    Metronidazole resistance is a key factor associated with Helicobacter pylori treatment failure. Although this resistance is mainly associated with mutations in the rdxA and frxA genes, the question of whether metronidazole resistance is caused by the inactivation of frxA alone is still debated. Furthermore, it is unclear whether there are other mutations involved in addition to the two genes that are associated with resistance. A metronidazole-resistant strain was cultured from the metronidazole-susceptible H. pylori strain 26695-1 by exposure to low concentrations of metronidazole. The genome sequences of both susceptible and resistant H. pylori strains were determined by Illumina next-generation sequencing, from which putative candidate resistance mutations were identified. Natural transformation was used to introduce PCR products containing candidate mutations into the susceptible parent strain 26695-1, and the metronidazole MIC was determined for each strain. Mutations in frxA (hp0642), rdxA (hp0954), and rpsU (hp0562) were confirmed by the Sanger method. The mutated sequence in rdxA was successfully transformed into strain 26695-1, and the transformants showed resistance to metronidazole. The transformants containing a single mutation in rdxA showed a low MIC (16 mg/liter), while those containing mutations in both rdxA and frxA showed a higher MIC (48 mg/liter). No transformants containing a single mutation in frxA or rpsU were obtained. Next-generation sequencing was used to identify mutations related to drug resistance. We confirmed that the mutations in rdxA are mainly associated with metronidazole resistance, and mutations in frxA are able to enhance H. pylori resistance only in the presence of rdxA mutations. Moreover, mutations in rpsU may play a role in metronidazole resistance.

  7. Randomized pharmacokinetic and drug–drug interaction studies of ceftazidime, avibactam, and metronidazole in healthy subjects

    PubMed Central

    Das, Shampa; Li, Jianguo; Armstrong, Jon; Learoyd, Maria; Edeki, Timi

    2015-01-01

    We assessed pharmacokinetic and safety profiles of ceftazidime–avibactam administered ± metronidazole, and whether drug–drug interactions exist between ceftazidime and avibactam, or ceftazidime-avibactam and metronidazole. The first study (NCT01430910) involved two cohorts of healthy subjects. Cohort 1 received ceftazidime–avibactam (2000–500 mg) as a single infusion or as multiple intravenous infusions over 11 days to evaluate ceftazidime–avibactam pharmacokinetics. Cohort 2 received ceftazidime, avibactam, or ceftazidime–avibactam over 4 days to assess drug–drug interaction between ceftazidime and avibactam. The second study (NCT01534247) assessed interaction between ceftazidime–avibactam and metronidazole in subjects receiving ceftazidime–avibactam (2000–500 mg), metronidazole (500 mg), or metronidazole followed by ceftazidime–avibactam over 4 days. In all studies, subjects received a single-dose on the first and final days, and multiple-doses every 8 h on intervening days. Concentration-time profiles for ceftazidime and avibactam administered as single- or multiple-doses separately or together with/without metronidazole were similar. There was no evidence of time-dependent pharmacokinetics or accumulation. In both interaction studies, 90% confidence intervals for geometric least squares mean ratios of area under the curve and maximum plasma concentrations for each drug were within the predefined interval (80–125%) indicating no drug–drug interaction between ceftazidime and avibactam, or ceftazidime–avibactam and metronidazole. There were no safety concerns. In conclusion, pharmacokinetic parameters and safety of ceftazidime, avibactam, and metronidazole were similar after single and multiple doses with no observed drug–drug interaction between ceftazidime and avibactam, or ceftazidime–avibactam and metronidazole. PMID:26516584

  8. Draft Genome Sequence of a Metronidazole-Susceptible Atopobium vaginae Isolate

    PubMed Central

    Schuyler, Jessica A.; Mordechai, Eli; Adelson, Martin E.; Gygax, Scott E.

    2015-01-01

    We report the draft genome sequence of a vaginal isolate of Atopobium vaginae vaginae (strain 44061), an organism linked to bacterial vaginosis (BV), the most common gynecological infection in the United States. This species is often highly resistant to metronidazole, which is a front-line therapy for BV. Strain 44061 is a metronidazole-susceptible isolate (MIC, 16 µg/ml), and its genome sequence will be useful for comparative studies to elucidate the molecular basis of metronidazole resistance in this species. PMID:26337886

  9. Influence of Metronidazole, CO, CO2, and Methanogens on the Fermentative Metabolism of the Anaerobic Fungus Neocallimastix sp. Strain L2

    PubMed Central

    Marvin-Sikkema, Femke D.; Rees, Elizabeth; Kraak, Marjan N.; Gottschal, Jan C.; Prins, Rudolf A.

    1993-01-01

    The effects of metronidazole, CO, methanogens, and CO2 on the fermentation of glucose by the anaerobic fungus Neocallimastix sp. strain L2 were investigated. Both metronidazole and CO caused a shift in the fermentation products from predominantly H2, acetate, and formate to lactate as the major product and caused a lower glucose consumption rate and cell protein yield. An increased lactate dehydrogenase activity and a decreased hydrogenase activity were observed in cells grown under both culture conditions. In metronidazole-grown cells, the amount of hydrogenase protein was decreased compared with the amount in cells grown in the absence of metronidazole. When Neocallimastix sp. strain L2 was cocultured with the methanogenic bacterium Methanobrevibacter smithii, the fermentation pattern changed in the opposite direction: H2 and acetate production increased at the expense of the electron sink products lactate, succinate, and ethanol. A concomitant decrease in the enzyme activities leading to these electron sink products was observed, as well as an increase in the glucose consumption rate and cell protein yield, compared with those of pure cultures of the fungus. Low levels of CO2 in the gas phase resulted in increased H2 and lactate formation and decreased production of formate, acetate, succinate, and ethanol, a decreased glucose consumption rate and cell protein yield, and a decrease in most of the hydrogenosomal enzyme activities. None of the tested culture conditions resulted in changed quantities of hydrogenosomal proteins. The results indicate that manipulation of the pattern of fermentation in Neocallimastix sp. strain L2 results in changes in enzyme activities but not in the proliferation or disappearance of hydrogenosomes. Images PMID:16349022

  10. Novel hybrids of metronidazole and quinolones: synthesis, bioactive evaluation, cytotoxicity, preliminary antimicrobial mechanism and effect of metal ions on their transportation by human serum albumin.

    PubMed

    Cui, Sheng-Feng; Peng, Li-Ping; Zhang, Hui-Zhen; Rasheed, Syed; Vijaya Kumar, Kannekanti; Zhou, Cheng-He

    2014-10-30

    A novel series of hybrids of metronidazole and quinolones as antimicrobial agents were designed and synthesized. Most prepared compounds exhibited good or even stronger antimicrobial activities in comparison with reference drugs. Furthermore, these highly active metronidazole-quinolone hybrids showed appropriate ranges of pKa, log P and aqueous solubility to pharmacokinetic behaviors and no obvious toxicity to A549 and human hepatocyte LO2 cells. Their competitive interactions with metal ions to HSA revealed that the participation of Mg(2+) ion in compound 7d-HSA association could result in a concentration increase of free compound 7d. Molecular modeling and experimental investigation of compound 7d with DNA suggested that possible antibacterial mechanism might be in relation with multiple binding sites between bioactive molecules and topo IV-DNA complex.

  11. Severe hepatotoxicity associated with the combination of spiramycin plus metronidazole.

    PubMed

    Hussein, Rola; El-Halabi, Mustapha; Ghaith, Ola; Jurdi, Nawaf; Azar, Cecilio; Mansour, Nabil; Sharara, Ala I

    2011-03-01

    Drug-induced liver injury (DILI) is a leading cause of acute liver failure and is the most frequent reason for post-marketing drug withdrawal. The spectrum of liver injury is wide, ranging from mild and subclinical injury, noticeable only on routine biochemical testing, to fulminant liver failure and death. Antibiotics, as a group, are a leading cause of DILI. We herein describe 4 patients who developed moderate to severe hepatotoxicity after exposure to a commercially - available combination of two antibiotics - spiramycin and metronidazole - commonly used for the treatment and prevention of periodontal infections. No other aetiology for liver injury could be identified in all cases. Two patients recovered spontaneously, and two had a more severe course, one responding to corticosteroids and mycophenolate mofetil and the other requiring liver transplantation for subacute massive necrosis.

  12. Discriminative Dissolution Method for Benzoyl Metronidazole Oral Suspension.

    PubMed

    da Silva, Aline Santos; da Rosa Silva, Carlos Eduardo; Paula, Fávero Reisdorfer; da Silva, Fabiana Ernestina Barcellos

    2016-06-01

    A dissolution method for benzoyl metronidazole (BMZ) oral suspensions was developed and validated using a high-performance liquid chromatography (HPLC) method. After determination of sink conditions, dissolution profiles were evaluated using different dissolution media and agitation speeds. The sample insertion mode in dissolution media was also evaluated. The best conditions were obtained using a paddle, 50 rpm stirring speed, simulated gastric fluid (without pepsin) as the dissolution medium, and sample insertion by a syringe. These conditions were suitable for providing sink conditions and discriminatory power between different formulations. Through the tested conditions, the results can be considered specific, linear, precise, accurate, and robust. The dissolution profiles of five samples were compared using the similarity factor (f 2) and dissolution efficiency. The dissolution kinetics were evaluated and described by the Weibull model. Whereas there is no monograph for this pharmaceutical formulation, the dissolution method proposed can be considered suitable for quality control and dissolution profile comparison of different commercial formulations.

  13. Influence of Hydroxypropyl Methylcellulose on Metronidazole Crystallinity in Spray-Congealed Polyethylene Glycol Microparticles and Its Impact with Various Additives on Metronidazole Release.

    PubMed

    Oh, Ching Mien; Heng, Paul Wan Sia; Chan, Lai Wah

    2015-12-01

    The purpose of this study was to investigate the effect of a hydrophilic polymer, hydroxypropyl methylcellulose (HPMC), on the crystallinity and drug release of metronidazole (MNZ) in spray-congealed polyethylene glycol (PEG) microparticles and to further modify the drug release using other additives in the formulation. HPMC has been used in many pharmaceutical formulations and processes but to date, it has not been employed as an additive in spray congealing. Crystallinity of a drug is especially important to the development of pharmaceutical products as active pharmaceutical ingredients (APIs) are mostly crystalline in nature. A combination of X-ray diffractometry, differential scanning calorimetry, Raman spectroscopy and Fourier transform-infrared spectroscopy (FT-IR) spectroscopy was employed to investigate the degree of crystallinity and possible solid-state structure of MNZ in the microparticles. The microparticles with HPMC were generally spherical. Spray congealing decreased MNZ crystallinity, and the presence of HPMC reduced the drug crystallinity further. The reduction in MNZ crystallinity was dependent on the concentration of HPMC. Smaller HPMC particles also resulted in a greater percentage reduction in MNZ crystallinity. Appreciable modification to MNZ release could be obtained with HPMC. However, this was largely attributed to the role of HPMC in forming a diffusion barrier. Further modification of drug release from spray-congealed PEG-HPMC microparticles was achieved with the addition of 5% w/w dicalcium phosphate but not with magnesium stearate, methyl cellulose, polyvinylpyrrolidone, silicon dioxide and sodium oleate/citric acid. Dicalcium phosphate facilitated formation of the diffusion barrier.

  14. EVALUATION OF ALGINATE MICROSPHERES WITH METRONIDAZOLE OBTAINED BY THE SPRAY DRYING TECHNIQUE.

    PubMed

    Szekalska, Marta; Winnicka, Katarzyna; Czajkowska-Kośnik, Anna; Sosnowska, Katarzyna; Amelian, Aleksandra

    2015-01-01

    In the present study, nine formulations (F1-F9) of alginate microspheres with metronidazole were prepared by the spray drying technique with using different drug:polymer ratio (1:2, 1:1, 2:1) and different sodium alginate concentration (1, 2, 3%). The obtained microspheres were characterized for size, morphology, drug loading, (potential and swelling degree. Mucoadhesive properties were examined using texture analyzer and three different models of adhesive layers--gelatin discs, mucin gel and porcine vaginal mucosa. In vitro drug release, mathematical release profile and physical state of microspheres were also evaluated. The obtained results indicate that sodium alginate is a suitable polymer for developing mucoadhesive dosage forms of metronidazole. The optimal formulation F3 (drug:polymer ratio 1:2 and 1% alginate solution) was characterized by the highest metronidazole loading and sustained drug release. The results of this study indicate promising potential of ALG microspheres as alternative dosage forms for metronidazole delivery.

  15. One-Gram, Single-Dose Metronidazole (Flagyl) for Trichomonal Vaginitis.

    ERIC Educational Resources Information Center

    Moore, Jennifer R.

    1979-01-01

    Effective single-dose treatment of trichomonal vaginitis is reported. Large single-dose treatment with metronidazole was found to be effective and avoided the side effects occurring with multidose treatment. (MJB)

  16. Challenges in oral administration of metronidazole dissolved in drinking water to rhesus monkeys (Macaca mulatta).

    PubMed

    Labberton, Linda; Bakker, Jaco; Klomp, Rianne; Langermans, Jan A M; van Geijlswijk, Ingeborg M

    2013-06-01

    Intestinal pathogens such as Entamoeba spp. and Giardia spp. protozoans are not uncommon among rhesus macaques (Macaca mulatta) in research facilities. These infections affect the health of the macaques, potentially causing severe diarrhea, and also pose a risk of zoonotic transmission to human caretakers. Infections must therefore be treated, but no standard treatment for intestinal protozoans in macaques has been developed. Metronidazole is commonly used to treat infections with Giardia spp. and Entamoeba spp. in veterinary medicine, but evidence-based information on effectiveness and dosages for nonhuman primates is lacking, and administration of drugs to nonhuman primates is challenging. The authors designed a study to determine whether oral administration of metronidazole dissolved in drinking water would be successful in rhesus macaques. They monitored daily fluid intake of macaques given water with or without metronidazole and with or without flavored syrup. Metronidazole addition, with or without flavored syrup, resulted in a decrease in fluid intake. Although it was possible to administer metronidazole in drinking water to some macaques, the authors conclude that this strategy is not a practical clinical method because of variation in the amount of water and metronidazole ingested by the macaques.

  17. Intestinal Fatty-Acid Binding Protein and Metronidazole Response in Premature Infants

    PubMed Central

    Sampson, Mario R.; Bloom, Barry T.; Arrieta, Antonio; Capparelli, Edmund; Benjamin, Daniel K.; Smith, P. Brian; Kearns, Gregory L.; van den Anker, John; Cohen-Wolkowiez, Michael

    2014-01-01

    Objectives In premature infants with suspected intra-abdominal infection, biomarkers for treatment response to antimicrobial therapy are lacking. Intestinal fatty acid-binding protein (I-FABP) is specific to the enterocyte and is released in response to intestinal mucosal injury. I-FABP has not been evaluated as a surrogate marker of disease response to antimicrobial therapy. We examined the relationship between metronidazole exposure and urinary I-FABP concentrations in premature infants with suspected intra-abdominal infection. Study design We conducted an intravenous metronidazole pharmacokinetic study, collecting ≤3 urine samples per infant for I-FABP concentration measurements. We analyzed the relationship between I-FABP concentrations and measures of metronidazole exposure and pharmacokinetics, maturational factors, and other covariates. Results Twenty-six samples from 19 premature infants were obtained during metronidazole treatment. When analyzed without regard to presence of necrotic gastrointestinal disease, there were no significant associations between predictor variables and I-FABP concentrations. However, when the sample was limited to premature infants with necrotic gastrointestinal disease, an association was found between average predicted metronidazole concentration and I-FABP concentration (p=0.006). Conclusion While a predictive association between urinary I-FABP and metronidazole systemic exposure was not observed, the data suggest the potential of this endogenous biomarker to serve as a pharmacodynamic surrogate for antimicrobial treatment of serious abdominal infections in neonates and infants. PMID:25318626

  18. Resistance of Helicobacter pylori to tetracycline, amoxicillin, clarithromycin and metronidazole in Israeli children and adults.

    PubMed

    Peretz, Avi; Paritsky, Maya; Nasser, Omar; Brodsky, Diana; Glyatman, Tatyana; Segal, Sofia; On, Avi

    2014-08-01

    The aim of this study was to examine Helicobacter pylori-resistance rate to different antibiotics: tetracycline, amoxicillin, clarithromycin and metronidazole, and to compare eradication rates in adults and children in Israel. The study was based on the hypothesis of high-resistance rates to clarithromycin and metronidazole especially in adults and overall low-resistance rates to tetracycline and amoxicillin. One seventy six biopsies from patients with dyspeptic symptoms were cultured of which 100 were from adults (19-79 years) and 76 from children (7-17 years). All positive cultures were examined by Epsilometer test for MIC determination against tetracycline, amoxicillin, clarithromycin and metronidazole. 48.3% (85 out of 176) were H. pylori positive, of which 44% were from adults and 54% from children. Antibiotic resistance was seen in 31 out of 44 (70.5%) for metronidazole, 1 out of 44 (2.3%) for amoxicillin, 10 out of 44 (22.3%) for clarithromycin and 1 out of 44 (2.3%) for tetracycline among adults. Antibiotic resistance was seen in 10 out of 41 (24.4%) for metronidazole, 5 out of 41 (12.2%) for amoxicillin, 10 out of 41 (24.4%) for clarithromycin and 1 out of 41 (2.4%) for tetracycline among children. High rates of H. pylori resistance to metronidazole and clarithromycin was found especially among adults. Therefore, to increase the success rate of anti-H. pylori treatment, other classes of antibiotics need to be considered.

  19. Electrochemical Determination of Metronidazole in Tablet Samples Using Carbon Paste Electrode

    PubMed Central

    Nikodimos, Yosef

    2016-01-01

    Cyclic voltammetric investigation of metronidazole at carbon paste electrode revealed an irreversible reduction peak centered at about −0.4 V. Observed peak potential shift with pH in the range 2.0 to 8.5 indicated the involvement of protons during the reduction of metronidazole, whereas the peak potential shift with scan rate in the range 10–250 mV/s confirmed the irreversibility of the reduction reaction. A better correlation coefficient for the dependence of peak current on the scan rate than on the square root of scan rate indicated an adsorption controlled kinetics. Under the optimized method and solution parameters, an excellent linearity between the reductive peak current and the concentration of metronidazole was observed in the concentration range 1.0 × 10−6 to 5.0 × 10−4 M with a correlation coefficient, method detection limit (based on s = 3σ), and limit of quantification of 0.999, 2.97 × 10−7 M and 9.91 × 10−7 M, respectively. Good recovery results for spiked metronidazole in tablet samples and selective determination of metronidazole in tablet formulations in the presence of selected potential interferents such as rabeprazole, omeprazole, and tinidazole confirmed the potential applicability of the developed method for the determination of metronidazole in real samples like pharmaceutical tablets. PMID:27119041

  20. ASSOCIATION OF CALCIUM HYDROXIDE AND METRONIDAZOLE IN THE TREATMENT OF DOG'S TEETH WITH CHRONIC PERIAPICAL LESION

    PubMed Central

    Panzarini, Sônia Regina; Souza, Valdir; Holland, Roberto; Dezan, Eloi

    2006-01-01

    One of the primary objectives of endodontic treatment of teeth with pulp necrosis is the elimination of microorganisms from the root canal system, as effectively as possible, especially in cases with chronic periapical lesions. AIM: The purpose of this study was to analyze the response of the periapical tissue of dogs' teeth with chronic periapical lesions to endodontic treatment performed with utilization of metronidazole, calcium hydroxide, and an association of both as root canal dressings. METHODOLOGY: Forty root canals were submitted to pulpectomy and the root canals were kept exposed to the oral environment for 6 months. Then, they were submitted to biomechanical preparation and divided into 4 study groups with 10 specimens: group I – no root canal dressing; group II – calcium hydroxide; group III – metronidazole; group IV – calcium hydroxide associated to metronidazole. After 15 days, the root canals were filled with Fill Canal sealer. After 90 days, the animals were killed and the especimens processed for histological analysis. RESULTS: Calcium hydroxide dressing provided a significantly better outcome compared to other experimental groups (α = 0.01). Also, the results of the association of metronidazole and calcium hydroxide were similar to those observed for the metronidazole group. The worst results were obtained by the no root canal dressing group. CONCLUSION: The use of metronidazole alone or associated with Calcium hydroxide, did not improve periapical healing when compared to Calcium hydroxide dressing. PMID:19089054

  1. Low antibiotic resistance among anaerobic Gram-negative bacteria in periodontitis 5 years following metronidazole therapy.

    PubMed

    Dahlen, G; Preus, H R

    2017-02-01

    The objective of this study was to assess antibiotic susceptibility among predominant Gram-negative anaerobic bacteria isolated from periodontitis patients who 5 years prior had been subject to mechanical therapy with or without adjunctive metronidazole. One pooled sample was taken from the 5 deepest sites of each of 161 patients that completed the 5 year follow-up after therapy. The samples were analyzed by culture. A total number of 85 anaerobic strains were isolated from the predominant subgingival flora of 65/161 patient samples, identified, and tested for antibiotic susceptibility by MIC determination. E-tests against metronidazole, penicillin, amoxicillin, amoxicillin + clavulanic acid and clindamycin were employed. The 73/85 strains were Gram-negative rods (21 Porphyromonas spp., 22 Prevotella/Bacteroides spp., 23 Fusobacterium/Filifactor spp., 3 Campylobacter spp. and 4 Tannerella forsythia). These were all isolated from the treated patients irrespective of therapy procedures (+/-metronidazole) 5 years prior. Three strains (Bifidobacterium spp., Propionibacterium propionicum, Parvimonas micra) showed MIC values for metronidazole over the European Committee on Antimicrobial Susceptibility Testing break point of >4 μg/mL. All Porphyromonas and Tannerella strains were highly susceptible. Metronidazole resistant Gram-negative strains were not found, while a few showed resistance against beta-lactam antibiotics. In this population of 161 patients who had been subject to mechanical periodontal therapy with or without adjunct metronidazole 5 years prior, no cultivable antibiotic resistant anaerobes were found in the predominant subgingival microbiota.

  2. Effect of temperature on the metronidazole BSA interaction: Multi-spectroscopic method

    NASA Astrophysics Data System (ADS)

    Chen, Jun; Jiang, Xin Yu; Chen, Xiao Qing; Chen, Yue

    2008-03-01

    The interaction between metronidazole and bovine serum albumin (BSA) was investigated using fluorescence spectroscopy (FS) and resonance light scattering spectroscopy (RLS). The apparent binding constants ( Ka) between metronidazole and BSA were 3.42 × 10 4 (20 °C), 5.78 × 10 4 (30 °C) and 8.23 × 10 4 L mol -1 (40 °C), and the binding sites values ( n) were 1.48 ± 0.03. The experimental results showed that the metronidazole could be inserted into the BSA, quenching the inner fluorescence by forming the metronidazole-BSA complex. The addition of increasing metronidazole to BSA solution leads to the gradual enhancement in RLS intensity, exhibiting the formation of the aggregate in solution. It was found that both static quenching and non-radiation energy transfer were the main reasons for the fluorescence quenching. The entropy change and enthalpy change were positive, which indicated that the interaction of metronidazole and BSA was driven mainly by hydrophobic forces. The process of binding was a spontaneous process in which Gibbs free energy change was negative.

  3. Optimization of metronidazole sustained-release films using D-optimal design.

    PubMed

    Peerapattana, Jomjai; Ngamsupsiri, Teeraphat; Cheucharoenvasuchai, Nopadol; Saikaew, Charnnarong

    2015-04-30

    The aim of this study was to develop sustained-release metronidazole films for periodontal pockets using a computer-aided statistical approach. The studied independent variables were the amount of polycaprolactone, metronidazole, hydroxypropylmethyl cellulose and glyceryl monostearate. The response of interest was the cumulative percentage release of metronidazole at 1, 2, 3, 4 and 5 days. The films were prepared using a melt method. The physicochemical properties and release profiles of the films were investigated. Model validation was also performed. The produced films were thin white sheets with a smooth and glossy surface. Each sheet had an average weight of 9.31 ± 0.10mg. The metronidazole was uniformly dispersed in the film, and the percentage of drug loading was 100.12 ± 4.38%. The thickness of the film was 325 ± 5.27 μm. The puncture strength, % elongation and Young's modulus were 11.58 ± 0.51 N/mm(2), 33.51 ± 3.61%, and 0.347 ± 0.02 1N/mm(2), respectively. The actual drug release profiles of the optimal formulation films were close to the predicted responses. Metronidazole was slowly released from the matrices over a period of at least 5 days. The release mechanism of the films followed Fickian diffusion. This study demonstrates that appropriate D-optimal design and optimization techniques can be successfully used in the development of metronidazole sustained-release films.

  4. Evidence for Lateral Transfer of Genes Encoding Ferredoxins, Nitroreductases, NADH Oxidase, and Alcohol Dehydrogenase 3 from Anaerobic Prokaryotes to Giardia lamblia and Entamoeba histolytica

    PubMed Central

    Nixon, Julie E. J.; Wang, Amy; Field, Jessica; Morrison, Hilary G.; McArthur, Andrew G.; Sogin, Mitchell L.; Loftus, Brendan J.; Samuelson, John

    2002-01-01

    Giardia lamblia and Entamoeba histolytica are amitochondriate, microaerophilic protists which use fermentation enzymes like those of bacteria to survive anaerobic conditions within the intestinal lumen. Genes encoding fermentation enzymes and related electron transport peptides (e.g., ferredoxins) in giardia organisms and amebae are hypothesized to be derived from either an ancient anaerobic eukaryote (amitochondriate fossil hypothesis), a mitochondrial endosymbiont (hydrogen hypothesis), or anaerobic bacteria (lateral transfer hypothesis). The goals here were to complete the molecular characterization of giardial and amebic fermentation enzymes and to determine the origins of the genes encoding them, when possible. A putative giardia [2Fe-2S]ferredoxin which had a hypothetical organelle-targeting sequence at its N terminus showed similarity to mitochondrial ferredoxins and the hydrogenosomal ferredoxin of Trichomonas vaginalis (another luminal protist). However, phylogenetic trees were star shaped, with weak bootstrap support, so we were unable to confirm or rule out the endosymbiotic origin of the giardia [2Fe-2S]ferredoxin gene. Putative giardial and amebic 6-kDa ferredoxins, ferredoxin-nitroreductase fusion proteins, and oxygen-insensitive nitroreductases each tentatively supported the lateral transfer hypothesis. Although there were not enough sequences to perform meaningful phylogenetic analyses, the unique common occurrence of these peptides and enzymes in giardia organisms, amebae, and the few anaerobic prokaryotes suggests the possibility of lateral transfer. In contrast, there was more robust phylogenetic evidence for the lateral transfer of G. lamblia genes encoding an NADH oxidase from a gram-positive coccus and a microbial group 3 alcohol dehydrogenase from thermoanaerobic prokaryotes. In further support of lateral transfer, the G. lamblia NADH oxidase and adh3 genes appeared to have an evolutionary history distinct from those of E. histolytica. PMID

  5. Metronidazole and hydroxymetronidazole central nervous system distribution: 2. cerebrospinal fluid concentration measurements in patients with external ventricular drain.

    PubMed

    Frasca, Denis; Dahyot-Fizelier, Claire; Adier, Christophe; Mimoz, Olivier; Debaene, Bertrand; Couet, William; Marchand, Sandrine

    2014-01-01

    This study explored metronidazole and hydroxymetronidazole distribution in the cerebrospinal fluid (CSF) of brain-injured patients. Four brain-injured patients with external ventricular drain received 500 mg of metronidazole over 0.5 h every 8 h. CSF and blood samples were collected at steady state over 8 h, and the metronidazole and hydroxymetronidazole concentrations were assayed by high-pressure liquid chromatograph. A noncompartmental analysis was performed. Metronidazole is distributed extensively within CSF, with a mean CSF to unbound plasma AUC0-τ ratio of 86% ± 16%. However, the concentration profiles in CSF were mostly flat compared to the plasma profiles. Hydroxymetronidazole concentrations were much lower than those of metronidazole both in plasma and in CSF, with a corresponding CSF/unbound plasma AUC0-τ ratio of 79% ± 16%. We describe here for the first time in detail the pharmacokinetics of metronidazole and hydroxymetronidazole in CSF.

  6. Removal of the antibiotic metronidazole by adsorption on various carbon materials from aqueous phase.

    PubMed

    Carrales-Alvarado, D H; Ocampo-Pérez, R; Leyva-Ramos, R; Rivera-Utrilla, J

    2014-12-15

    The adsorption of the antibiotic metronidazole (MNZ) on activated carbon (F400), activated carbon cloth (ACF), mesoporous activated carbon (CMK-3), and carbon nanotubes (MWCNT) was investigated in this work. The effect of the adsorbent-adsorbate interactions as well as the operating conditions (ionic strength, solution pH, temperature, chemical modification of the adsorbents by HNO3 treatment, and water matrix) on the adsorption capacity were analyzed to substantiate the adsorption mechanism. The adsorption capacity markedly varied as function of the carbon material, decreasing in the following order: F400>ACF>F400-HNO3>CMK-3>MWCNT>MWCNT-HNO3, and depended not only on their surface area and pore size distribution, but also on their chemical nature. The adsorption of MNZ was influenced by the solution pH, but was not significantly affected by the ionic strength and temperature. The adsorption of MNZ was enhanced when the MNZ solutions were prepared using wastewater. Therefore, the electrolytes present in the wastewater cooperated rather than competed with the MNZ molecules for the adsorption sites. Desorption equilibrium data of MNZ on all carbon materials demonstrated that the adsorption was reversible corroborating the weakness of the adsorbent-adsorbate interactions.

  7. Doxycycline, metronidazole and isotretinoin: Do they modify microRNA/mRNA expression profiles and function in murine T-cells?

    PubMed Central

    Becker, Eugenia; Bengs, Susan; Aluri, Sirisha; Opitz, Lennart; Atrott, Kirstin; Stanzel, Claudia; Castro, Pedro A. Ruiz; Rogler, Gerhard; Frey-Wagner, Isabelle

    2016-01-01

    Inflammatory bowel disease (IBD) may develop due to an inflammatory response to commensal gut microbiota triggered by environmental factors in a genetically susceptible host. Isotretinoin (acne therapy) has been inconsistently associated with IBD onset and flares but prior treatment with antibiotics, also associated with IBD development, complicates the confirmation of this association. Here we studied in mice whether doxycycline, metronidazole or isotretinoin induce epigenetic modifications, and consequently change T-cell mRNA expression and/or function directly after treatment and after a 4 week recovery period. Isotretinoin induced IL-10 signaling in Tregs and naive T-cells directly after treatment and reduced effector T-cell proliferation alone and in co-culture with Tregs. Metronidazole activated processes associated with anti-inflammatory pathways in both T-cell subsets directly after the treatment period whereas doxycycline induced an immediate pro-inflammatory expression profile that resolved after the recovery period. Long-term changes indicated an inhibition of proliferation by doxycycline and induction of beneficial immune and metabolic pathways by metronidazole. Persistent alterations in microRNA and mRNA expression profiles after the recovery period indicate that all three medications may induce long-term epigenetic modifications in both T-cell subsets. Yet, our data do not support the induction of a long-term pro-inflammatory phenotype in murine Tregs and naive T-cells. PMID:27853192

  8. Metronidazole decreases viability of DLD-1 colorectal cancer cell line.

    PubMed

    Sadowska, Anna; Krętowski, Rafał; Szynaka, Beata; Cechowska-Pasko, Marzanna; Car, Halina

    2013-10-01

    The aim of our study was to evaluate the impact of metronidazole (MTZ) on DLD-1 colorectal cancer cell (CRC) line. Toxicity of MTZ was determined by MTT test. Cells were incubated with MTZ used in different concentrations for 24, 48, and 72 hours. The effect of MTZ on DNA synthesis was measured as [3H]-thymidine incorporation. The morphological changes in human DLD-1 cell line were defined by transmission electron microscope OPTON 900. The influence of MTZ on the apoptosis of DLD-1 cell lines was detected by flow cytometry and fluorescence microscopy, while cell concentration, volume, and diameter were displayed by Scepter Cell Counter from Millipore. Our results show that cell viability was diminished in all experimental groups in comparison with the control, and the differences were statistically significant. We did not find any significant differences in [3H]-thymidine incorporation in all experimental groups and times of observation. Cytofluorimetric assays demonstrated a statistically significant increase of apoptotic rate in MTZ concentrations 10 and 50 μg/mL after 24 hours; 0.1, 10, 50, and 250 μg/mL after 48 hours; and in all concentrations after 72 hours compared with control groups. In the ultrastructural studies, necrotic or apoptotic cells were occasionally seen. In conclusion, MTZ affects human CRC cell line viability. The reduction of cell viability was consistent with the apoptotic test.

  9. Genotoxicity Revaluation of Three Commercial Nitroheterocyclic Drugs: Nifurtimox, Benznidazole, and Metronidazole

    PubMed Central

    Buschini, Annamaria; Ferrarini, Lisa; Franzoni, Susanna; Galati, Serena; Lazzaretti, Mirca; Mussi, Francesca; Northfleet de Albuquerque, Cristina; Maria Araújo Domingues Zucchi, Tânia; Poli, Paola

    2009-01-01

    Nitroheterocyclic compounds are widely used as therapeutic agents against a variety of protozoan and bacterial infections. However, the literature on these compounds, suspected of being carcinogens, is widely controversial. In this study, cytotoxic and genotoxic potential of three drugs, Nifurtimox (NFX), Benznidazole (BNZ), and Metronidazole (MTZ) was re-evaluated by different assays. Only NFX reduces survival rate in actively proliferating cells. The compounds are more active for base-pair substitution than frameshift induction in Salmonella; NFX and BNZ are more mutagenic than MTZ; they are widely dependent from nitroreduction whereas microsomal fraction S9 weakly affects the mutagenic potential. Comet assay detects BNZ- and NFX-induced DNA damage at doses in the range of therapeutically treated patient plasma concentration; BNZ seems to mainly act through ROS generation whereas a dose-dependent mechanism of DNA damaging is suggested for NFX. The lack of effects on mammalian cells for MTZ is confirmed also in MN assay whereas MN induction is observed for NFX and BNZ. The effects of MTZ, that shows comparatively low reduction potential, seem to be strictly dependent on anaerobic/hypoxic conditions. Both NFX and BNZ may not only lead to cellular damage of the infective agent but also interact with the DNA of mammalian cells. PMID:20981287

  10. Design, synthesis and molecular docking of salicylic acid derivatives containing metronidazole as a new class of antimicrobial agents.

    PubMed

    Guo, Zhi-Hua; Yin, Yong; Wang, Cong; Wang, Peng-Fei; Zhang, Xing-Tao; Wang, Zhong-Chang; Zhu, Hai-Liang

    2015-09-15

    A series of novel salicylic acid derivatives containing metronidazole as Staphylococcus aureus Tyrosyl-tRNA synthetase (TyrRS) inhibitors have been synthesized and evaluated their biology activities as potential antibacterial agents. Among these compounds, compound 5r exhibited the most potent antibacterial activity against Gram-positive (S. aureus ATCC 6538 and Bacillus subtilis ATCC 6633) and Gram-negative (Escherichia coli ATCC 35218 and Pseudomonas aeruginosa ATCC 13525) with MICs of 0.39-1.57 μg/mL and showed the most potent S. aureus Tyrosyl-tRNA synthetase inhibitory with 2.3 μM. Docking simulation was performed to insert compound 5r into the crystal structure of S. aureus Tyrosyl-tRNA synthetase active site to determine the probable binding model. These results suggested that compound 5r may be a promising antibacterial agent.

  11. Effects of mesocaval shunt on the pharmacokinetics of metronidazole in young rats.

    PubMed

    Guillé, Beatriz E Perez; Alvarez, Fernando Villegas; Toledo López, Alejandra R; Bravo-Luna, Miguel A Jiménez; Soriano-Rosales, Rosa E; Lares-Asseff, Ismael; Arrellin, Gerardo; Guillé, Maria G Pérez

    2005-01-01

    Prophylactic and therapeutic management of portosystemic encephalopathies is based on protein restriction in the diet, and the use of lactulose and antibiotics such as metronidazole. These actions intend to reduce the main source of intestinal ammonia production and release into the systemic circulation. The aim of this study was to evaluate the medium-term effects of mesocaval shunt on the pharmacokinetics of metronidazole in rats with healthy livers. Male Lewis rats were divided into two groups. The first group was subjected to mesocaval shunt (MCS) and the other employed as a control. The following tests were carried out in both groups: metronidazole pharmacokinetics, determination of ALT, AST, albumin, urea and ammonium, liver weight and histomorphology. A loss in body and liver weight was registered in rats subjected to MCS. AST levels also increased compared to controls. Significant differences in almost all pharmacokinetic parameters were detected between MCS and control rats, especially in Kel, AUC and Cmax. Modifications in metronidazole pharmacokinetics and liver weight changes without microstructural modification secondary to MCS were found. We suggest that individual drug-monitoring and pharmacokinetic analysis must be carried out in metronidazole medicated patients with modifications in portal circulation with or with out macro or micro liver structural alterations.

  12. Liquid chromatographic assay for metronidazole and tinidazole: pharmacokinetic and metabolic studies in human subjects.

    PubMed Central

    Nilsson-Ehle, I; Ursing, B; Nilsson-Ehle, P

    1981-01-01

    We developed methods for measuring metronidazole, its two major metabolites, and tinidazole in serum and urine. After treatment of each sample with an equal volume of 5% perchloric acid, the drugs were separated by reverse-phase high-pressure liquid chromatography (retention times, 6 to 18 min). Quantitation was based on spectrometry at 320 nm. These assays were sensitive, rapid, and specific, and recoveries from biological samples were quantitative. Metronidazole and tinidazole were given as rapid intravenous infusions to four healthy human volunteers. The biological half-lives of these two compounds were 5.4 and 11.1 h, respectively. The hydroxy metabolite of metronidazole appeared quickly in serum and was eliminated at a slow rate. The acetic acid metabolite of metronidazole was detected in serum at very low levels and only for a limited time. No metabolic products of tinidazole were found in serum samples. In urine, 43.7% of the administered dose of metronidazole was recovered over a period of 24 h (24.1% of the dose as the hydroxy metabolite, 12.0% as the acetic acid metabolite, and 7.6% as unchanged drug). Only 18.4% of the infused dose of tinidazole was eliminated in urine over a period of 72 h, and no metabolic products were detected. PMID:7294765

  13. Evaluation of metronidazole-loaded poly(3-hydroxybutyrate) membranes to potential application in periodontitis treatment.

    PubMed

    da Silva, Marcio A C; Oliveira, Renata N; Mendonça, Roberta Helena; Lourenço, Talita G B; Colombo, Ana Paula V; Tanaka, Marcelo N; Tude, Elena M O; da Costa, Marysilvia F; Thiré, Rossana Mara S M

    2016-01-01

    Guided tissue regeneration is a technique used for periodontium reconstruction. This technique uses barrier membranes, which prevent epithelial growth in the wound site and may also be used to release antibiotics, to protect the wound against opportunistic infections. Periodontal poly(3-hydroxybutyrate) membranes containing metronidazole (a drug used to help in infection control) were produced and characterized. The kinetic mechanism of the metronidazole delivery of leached and nonleached membrane as well as its cytotoxicity and structural integrity were evaluated. Poly(3-hydroxybutyrate) membranes containing 0.5-2 wt % of the drug and 20 wt % of the plasticizer were manufactured via compression molding. Based on morphological analysis, membranes loaded with 2% metronidazole were considered for detailed studies. The results revealed that metronidazole delivery by the leached membranes seemed to follow the Fick's law. Membranes were noncytotoxic. The amount of metronidazole delivered was in the range of the minimal inhibitory concentration for Porphyromonas gingivalis, and the membranes inhibited the proliferation of these bacteria. Besides, they maintained their mechanical resistance after 30 days of immersion in phosphate buffer at pH 7.4.

  14. Randomized, double-blind, comparative study of oral metronidazole and tinidazole in treatment of bacterial vaginosis

    PubMed Central

    Raja, Indu M.; Basavareddy, Asha; Mukherjee, Deepali; Meher, Bikash Ranjan

    2016-01-01

    Objective: To compare the efficacy and tolerability of oral metronidazole and tinidazole in patients with bacterial vaginosis (BV) using Amsel's criteria. Patients and Methods: This was a randomized double-blind study, conducted by the Departments of Pharmacology and Gynecology of a tertiary care teaching hospital. Patients diagnosed with BV received either tablet metronidazole 500 mg twice daily for 5 days or tablet tinidazole 500 mg once daily + one placebo for 5 days and instructed to come for follow-up at the 1st week and 4th week. They were categorized as cured, partially cured, and not cured based on Amsel's criteria at the end of the study and compared between two groups using Chi-square test. Results: A total 120 women were enrolled in the study, of which 114 completed the study. The treatment arms were comparable. The cure rate with low-dose tinidazole was significantly more compared to metronidazole at 4th week (P = 0.0013), but not at 1st week (P = 0.242). The adverse drug reactions were less with tinidazole compared to metronidazole. Conclusion: Tinidazole at lower dose offers a better efficacy than metronidazole in long-term cure rates and in preventing relapses with better side effect profile. PMID:28066102

  15. Molecular analysis of the relationship between specific vaginal bacteria and bacterial vaginosis metronidazole therapy failure.

    PubMed

    Wang, B; Xiao, B B; Shang, C G; Wang, K; Na, R S; Nu, X X; Liao, Q

    2014-10-01

    Bacterial vaginosis frequently persists, even after treatment. The role of some strains of bacteria associated with bacterial vaginosis treatment failure remains poorly defined. The aim of our study was to define the risk of bacterial vaginosis treatment failure, including pre-treatment detection of specific vaginal bacteria. Bacterial vaginosis is present when the Nugent score is ≥7 and the modified Amsel criteria is positive. Women with bacterial vaginosis were treated with intravaginal metronidazole gel nightly for 5 nights. The 454 pyrosequencing method was used to detect bacteria in vaginal fluid. By univariate analysis, a history of bacterial vaginosis, intrauterine device use and the presence of Facklamia, Corynebacterium and Veillonella were significantly associated with bacterial vaginosis treatment failure. Lactobacillus crispatus, Lactobacillus pentosus and Megasphaera were significantly associated with curing bacterial vaginosis. After logistic regression analysis and detection of these bacteria for test-of-cure, we found that women who had a history of bacterial vaginosis had a higher incidence of bacterial vaginosis treatment failure, whereas women with L. crispatus had a lower incidence of treatment failure. Post-treatment sexual activity was not associated with the treatment effect. Our data suggested that treatment failure may be not caused by drug resistance. Rather, it has a closer relationship with the failed restoration of lactobacilli.

  16. A simple reagent-free spectrophotometric assay for monitoring metronidazole therapy in aquarium water.

    PubMed

    Webb, D Harry; Marrero, Cynthia; Ellis, Helen; Merriwether, Lea; Dove, Alistair D M

    2013-09-01

    A reagent-free spectrophotometric assay was developed to measure the concentration of metronidazole (a 5-nitroimidazole) in both freshwater and seawater matrices. This assay is simple, repeatable, sensitive, and precise and is ideal for use when a rapid, selective test to determine metronidazole concentration in aqueous matrices is necessary. The assay was practically tested on a South American fishes display during treatment with metronidazole for an outbreak of the flagellated parasite Spironucleus in a mixed cichlid (family Cichlidae) and tetra (family Characidae) community. The assay clearly illustrated the course of treatment for the system during a real clinical application. The assay is not without limitations, as interferences can occur from other drugs in the matrix with similar absorbance spectra. Nonetheless, this type of assay illustrates the potential for use of native absorbance assays in aqueous matrices for this and other therapeutic compounds.

  17. Heterogeneity in the sensitivity of stocks and clones of Giardia to metronidazole and ornidazole.

    PubMed

    Majewska, A C; Kasprzak, W; De Jonckheere, J F; Kaczmarek, E

    1991-01-01

    The sensitivity in vitro to metronidazole and ornidazole of 7 stocks and of the cloned lines of 5 stocks of Giardia isolated from humans, rodents and monkeys was studied by the growth inhibition test. All 7 stocks of Giardia, irrespective of the host, differed in their sensitivity to these drugs, commonly used in therapy of human giardiasis. The differences were greater with ornidazole than with metronidazole. The 5 Giardia stocks from which clones were prepared were found to consist of populations with significantly (P less than 0.05) differing sensitivities to ornidazole and metronidazole. There was a positive correlation between high resistance in vitro to both drugs of all clones of one parent stock and treatment failures of giardiasis in the patient from which the parasite stock had been isolated. The spectra of sensitivity of Giardia to anti-giardial drugs may have implications concerning the suspected zoonotic character of human giardiasis.

  18. Lymphocyte proliferation kinetics and sister-chromatid exchanges in individuals treated with metronidazole.

    PubMed

    Elizondo, G; Montero, R; Herrera, J E; Hong, E; Ostrosky-Wegman, P

    1994-03-01

    Metronidazole, an effective agent for the treatment of protozoan infections, is frequently used in developing countries. However, the employment of this drug has been questioned in view of its mutagenicity in bacteria and carcinogenicity in mice. A genotoxic study was carried out in which cellular proliferation kinetics and the frequency of sister-chromatid exchanges were determined in human peripheral blood lymphocytes from 12 individuals treated with therapeutic doses of metronidazole. No effect was observed on mitotic index with the treatment, although a significant increase was found in three individuals after treatment. No increase of sister-chromatid exchanges was detected. The rate of lymphocyte proliferation kinetics showed an increase after the metronidazole treatment in all patients, indicating a possible immunostimulatory action.

  19. Coordination of metronidazole to Cu(II): Structural characterization of a mononuclear square-planar compound

    NASA Astrophysics Data System (ADS)

    Palmer, Joshua H.; Wu, Ja-Shin; Upmacis, Rita K.

    2015-07-01

    The reaction between metronidazole [1-(2-hydroxyethyl)-2-methyl-5-nitroimidazole, MET] and CuCl2ṡ2H2O in methanol solution has allowed isolation of blue crystals of composition Cu(MET)2Cl2ṡMeOH. These crystals have been shown by X-ray diffraction to consist of mononuclear square-planar trans-Cu(MET)2Cl2 molecules in which the metronidazole ligands are trans to each other, as are the Cl ligands. The structure of this compound is very different from other compounds that have been obtained from the reaction between CuCl2ṡ2H2O and metronidazole, namely [Cu(MET)2(μ-Cl)Cl]2 and [Cu(MET)2(μ-Cl)(OH2)]2[Cl]2, which are dimers featuring bridging chloride ligands.

  20. Evaluation of early fetal exposure to vaginally-administered metronidazole in pregnant cynomolgus monkeys.

    PubMed

    Thompson, Kary E; Newcomb, Deanna L; Moffat, Graeme J; Zalikowski, Julie; Chellman, Gary J; McNerney, Mary Ellen

    2016-01-01

    Given concern about potential embryo-fetal harm following seminal exposure to drugs with teratogenic potential, pharmaceutical companies use theoretical calculations to estimate seminal concentrations, maternal exposure, and distribution across the placenta to the embryo-fetal compartment for risk assessment. However, it is plausible that there are additional mechanisms whereby the conceptus is exposed. In order to determine if theoretical calculations are sufficiently conservative to predict embryo-fetal exposure from drugs in semen, pregnant cynomolgus monkeys were given a vaginal dose of metronidazole during the early fetal period and cesarean-sectioned. Maternal, fetal, and amniotic fluid samples were analyzed for metronidazole and 2-hydroxymetronidazole. Exposure to metronidazole and its metabolite were comparable in all matrices. These data demonstrated no preferential transfer mechanism to conceptus following intravaginal administration of a small molecule drug; and therefore, suggest that traditional modeling for embryo-fetal exposure to drugs in semen in support of risk assessment for pharmaceutical agents is sufficiently conservative.

  1. Metronidazole Appears Not to Be a Human Teratogen: Review of Literature

    PubMed Central

    Struthers, Barbara J.

    1997-01-01

    Metronidazole is used to treat trichomoniasis, bacterial vaginosis, and other diseases. As is the case with many drugs, physicians often hesitate to use it during pregnancy, particularly in the first trimester. A review of the nearly four decades' worth of published literature on metronidazole use in pregnant women indicates that it is not teratogenic, regardless of the trimester in which it is used. On the other hand, a number of published studies indicate that bacterial vaginosis and trichomoniasis are associated with preterm birth and low birth weight. Treatment of these conditions with metronidazole during pregnancy may decrease the incidence of preterm birth and low birth weight, thus potentially decreasing the complications that can result from prematurity. PMID:18476180

  2. The effect of 3-(biphenyl-4-yl)-3-hydoxyquinuclidine (BPQ-OH) and metronidazole on Trichomonas vaginalis: a comparative study.

    PubMed

    Rocha, Débora Afonso Silva; de Andrade Rosa, Ivone; Urbina, Julio A; de Souza, Wanderley; Benchimol, Marlene

    2014-06-01

    Trichomonas vaginalis causes trichomoniasis in humans, a sexually transmitted disease commonly treated with metronidazole (MTZ), a drug that presents some toxicity, causing undesirable side effects. In addition, an increase in metronidazole-resistant parasites has been reported. Thus, the development of alternative treatment is recommended. To date, the search for antiparasitic drugs has been based on different approaches: identification of active natural products, identification of parasite targets, and the use of available compounds active against other pathogenic microorganisms. Here, we analyzed the in vitro antiproliferative and ultrastructural effects on T. vaginalis of BPQ-OH, a hydroxiquinuclidine derivative that inhibits squalene synthase and is active against several protozoa and fungi. We also compared the effects of BPQ-OH on T. vaginalis and mammalian cells with those of MTZ. We found that BPQ-OH inhibits in vitro proliferation of T. vaginalis, with an IC50 of 46 μM after 24 h. Although this IC50 is 16 times higher than that of MTZ (1.8 μM), BPQ-OH is less toxic for human cell lines than MTZ, with LC50 values of 2,300 and 70 μM, and selective indexes of 50 and 39, respectively. Ultrastructural analyses demonstrated that BPQ-OH induced alterations in T. vaginalis, such as rounded and wrinkled cells, membrane blebbing and intense vacuolization, leading to cell death, whereas MTZ also caused significant changes, including a decrease in hydrogenosomes size and endoflagellar forms. Our observations identify BPQ-OH as a promising leading compound for the development of novel anti-T. vaginalis drugs and highlight the need for further testing this molecule using experimentally infected animals.

  3. Symmetrical drug-related intertriginous and flexural exanthema (SDRIFE) induced by oral metronidazole.

    PubMed

    Şikar Aktürk, Aysun; Bayramgürler, Dilek; Salman, Selma; Yıldız, Kürşat Demir; Odyakmaz Demirsoy, Evren

    2014-12-01

    Baboon syndrome is a special form of systemic contact dermatitis to systemic or local administration of contact allergens. Baboon syndrome without known previous cutaneous sensitisation was also described as drug-related baboon syndrome or symmetrical drug-related intertriginous and flexural exanthema (SDRIFE). The major drugs causing SDRIFE was beta-lactam antibiotic such as amoxicillin and ampicillin. We report a case of 16-year-old woman who developed pruritic eruptions after oral metronidazole treatment for diarrhea. She was diagnosed SDRIFE according to her clinical and histopathological findings. To our knowledge, our patient is the first case who developed SDRIFE due to metronidazole in the literature.

  4. A new fluorescent probe with a large turn-on signal for imaging nitroreductase in tumor cells and tissues by two-photon microscopy.

    PubMed

    Liu, Zhan-Rong; Tang, Yonghe; Xu, An; Lin, Weiying

    2017-03-15

    Hypoxia is the important characteristic of solid tumors, and it may cause the bioactivity of nitroreductase (NTR) to display an elevated level. Hence, the development of effective monitoring methods of NTR in living systems is of great importance for detecting the occurrence and progress of tumors. Toward this goal, a novel two-photon fluorescence turn-on NTR probe GCTPOC-HY, based on the two-photon platform GCTPOC and the NTR recognition site p-nitrobenzyl ether, is designed and synthesized. The probe GCTPOC-HY exhibits eminent properties such as high sensitivity and selectivity, highly stable photo-stability, and low cytotoxicity. Besides, the probe responds to 1.5μg/mL NTR with a 130-fold fluorescence enhancement, which is larger than the reported two-photon fluorescent NTR probes. Moreover, the probe GCTPOC-HY is suitable for fluorescence imaging of NTR in living cells by one- and two-photon modes. Importantly, the probe GCTPOC-HY is successfully applied to monitor NTR in the tumor tissues with a significant fluorescence signal and a penetration depth of 70µm by using two-photon microscopy.

  5. Impaired parasite attachment as fitness cost of metronidazole resistance in Giardia lamblia.

    PubMed

    Tejman-Yarden, Noa; Millman, Maya; Lauwaet, Tineke; Davids, Barbara J; Gillin, Frances D; Dunn, Linda; Upcroft, Jacqueline A; Miyamoto, Yukiko; Eckmann, Lars

    2011-10-01

    Infections with the diarrheagenic protozoan pathogen Giardia lamblia are most commonly treated with metronidazole (Mz). Treatment failures with Mz occur in 10 to 20% of cases and Mz resistance develops in the laboratory, yet clinically, Mz-resistant (Mz(r)) G. lamblia has rarely been isolated from patients. To understand why clinical Mz(r) isolates are rare, we questioned whether Mz resistance entails fitness costs to the parasite. Our studies employed several newly generated and established isogenic Mz(r) cell lines with stable, high-level resistance to Mz and significant cross-resistance to tinidazole, nitazoxanide, and furazolidone. Oral infection of suckling mice revealed that three of five Mz(r) cell lines could not establish infection, while two Mz(r) cell lines infected pups, albeit with reduced efficiencies. Failure to colonize resulted from a diminished capacity of the parasite to attach to the intestinal mucosa in vivo and to epithelial cells and plastic surfaces in vitro. The attachment defect was related to impaired glucose metabolism, since the noninfectious Mz(r) lines consumed less glucose, and glucose promoted ATP-independent parasite attachment in the parental lines. Thus, resistance of Giardia to Mz is accompanied by a glucose metabolism-related attachment defect that can interfere with colonization of the host. Because glucose-metabolizing pathways are important for activation of the prodrug Mz, it follows that a fitness trade-off exists between diminished Mz activation and reduced infectivity, which may explain the observed paucity of clinical Mz(r) isolates of Giardia. However, the data also caution that some forms of Mz resistance do not markedly interfere with in vivo infectivity.

  6. Draft Genome Sequence of a Metronidazole-Resistant Derivative of Gardnerella vaginalis Strain ATCC 14019

    PubMed Central

    Schuyler, Jessica A.; Mordechai, Eli; Adelson, Martin E.; Gygax, Scott E.

    2015-01-01

    We report the genome sequence of a metronidazole-resistant derivative of Gardnerella vaginalis ATCC 14019. This strain was obtained after serial selection to increase the MIC from 4 to ≥500 µg/ml. Two coding changes, in genes encoding a response regulator and an NAD+ synthetase, arose during selection. PMID:26564054

  7. Systemic moxifloxacin vs amoxicillin/metronidazole adjunct to non-surgical treatment in generalized aggressive periodontitis

    PubMed Central

    Gurgan, Cem-Abdulkadir

    2015-01-01

    Background The objective of this randomized clinical study was to evaluate the effect of systemic administration of moxifloxacin compared to amoxicillin and metronidazole, combined with non-surgical treatment in patients with generalized aggressive periodontitis (GAgP) in a 6-month follow-up. Material and Methods A total of 39 systemically healthy patients with GAgP were evaluated in this randomized clinical trial. Periodontal parameters were recorded at the baseline during the 1st, 3rd and 6th month. Patients received either 400 mg of moxifloxacin per os once daily or 500 mg of metronidazole and 500 mg amoxicillin per os three times daily for 7 days consecutively. Results No significant differences between groups were found in any parameters at the baseline. Both groups led to a statistically significant decrease in all clinical periodontal parameters compared to the baseline (PI, p<0.001 and GI, PD, BOP, CAL, p<0.01). There were no differences between the 1st and 3rd months or the 3rd and 6th months for clinical parameters in the groups. Also, no intergroup difference was observed in any parameters at any time, except the gingival index at 6th months. Conclusions Systemic administration of moxifloxacin as an adjunct to non-surgical treatment significantly improves clinical outcomes and provides comparable clinical improvement with less adverse events to that of combination of amoxicillin and metronidazole in the treatment of GAgP. Key words: Aggressive periodontitis, amoxicillin, metronidazole, moxifloxacin, nonsurgical periodontal debridement. PMID:26034931

  8. Molecular and Proteomic Analysis of Levofloxacin and Metronidazole Resistant Helicobacter pylori

    PubMed Central

    Hanafi, Aimi; Lee, Woon Ching; Loke, Mun Fai; Teh, Xinsheng; Shaari, Ain; Dinarvand, Mojdeh; Lehours, Philippe; Mégraud, Francis; Leow, Alex Hwong Ruey; Vadivelu, Jamuna; Goh, Khean Lee

    2016-01-01

    Antibiotic resistance in bacteria incurs fitness cost, but compensatory mechanisms may ameliorate the cost and sustain the resistance even under antibiotics-free conditions. The aim of this study was to determine compensatory mechanisms of antibiotic resistance in H. pylori. Five strains of levofloxacin-sensitive H. pylori were induced in vitro to develop resistance. In addition, four pairs of metronidazole-sensitive and -resistant H. pylori strains were isolated from patients carrying dual H. pylori populations that consist of both sensitive and resistant phenotypes. Growth rate, virulence and biofilm-forming ability of the sensitive and resistant strains were compared to determine effects of compensatory response. Proteome profiles of paired sensitive and resistant strains were analyzed by liquid chromatography/mass spectrophotometry (LC/MS). Although there were no significant differences in growth rate between sensitive and resistant pairs, bacterial virulence (in terms of abilities to induce apoptosis and form biofilm) differs from pair to pair. These findings demonstrate the complex and strain-specific phenotypic changes in compensation for antibiotics resistance. Compensation for in vitro induced levofloxacin resistance involving mutations of gyrA and gyrB was functionally random. Furthermore, higher protein translation and non-functional protein degradation capabilities in naturally-occuring dual population metronidazole sensitive-resistant strains may be a possible alternative mechanism underlying resistance to metronidazole without mutations in rdxA and frxA. This may explain the lack of mutations in target genes in ~10% of metronidazole resistant strains. PMID:28018334

  9. Development and Characterization of Bioadhesive Gel of Microencapsulated Metronidazole for Vaginal Use

    PubMed Central

    Bhabani Shankar, Nayak; Prasant Kumar, Rout; Udaya Kumar, Nayak; Benoy Brata, Bhowmik

    2010-01-01

    The present study concerned with the development and characterization of metronidazole microcapsules prepared by thermal change method using different ratios (1:1, 1:2 and 1:4) of ethyl cellulose in order to select the best microcapsule formulation with a good encapsulation efficiency and drug release profile. The obtained microcapsules were discrete, spherical with free flowing properties and evaluated for particle size, shape, flow properties, wall thickness, drug encapsulation efficiency and in vitro release performance. The drug carrier interactions were investigated in solid state by FT-IR spectroscopy and scanning electron microscopy. The microcapsules with a narrow size range of 23-68 μm showed higher encapsulation efficiency. The selected microcapsule formulation, MC3 (Drug polymer ratio 1:4) was employed for gel formulation with a variety of carbopol polymers (carbopol-934, 940, 974 and 980) by mechanical stirring method in order to develop a sustained release microencapsulated metronidazole microcapsules-containing bioadhesive gel. The prepared bioadhesive gels were evaluated for pH, spreadability, extrudability, viscosity, vaginal irritation, in vitro drug release, bioadhesion, accelerated stability and in vitro drug release kinetic. In vitro experiments indicated a sustained release over 24 h and an acceptable bioadhesion quality for formulation F3. Hence, it can be concluded that the formulation F3 has potential to deliver metronidazole in a controlled and constant manner for prolong period over other formulations and can be adopted for a successful delivery of metronidazole for vaginal use. PMID:24363730

  10. Effects of oral administration of metronidazole and doxycycline on olfactory capabilities of explosives detection dogs.

    PubMed

    Jenkins, Eileen K; Lee-Fowler, Tekla M; Angle, T Craig; Behrend, Ellen N; Moore, George E

    2016-08-01

    OBJECTIVE To determine effects of oral administration of metronidazole or doxycycline on olfactory function in explosives detection (ED) dogs. ANIMALS 18 ED dogs. PROCEDURES Metronidazole was administered (25 mg/kg, PO, q 12 h for 10 days); the day prior to drug administration was designated day 0. Odor detection threshold was measured with a standard scent wheel and 3 explosives (ammonium nitrate, trinitrotoluene, and smokeless powder; weight, 1 to 500 mg) on days 0, 5, and 10. Lowest repeatable weight detected was recorded as the detection threshold. There was a 10-day washout period, and doxycycline was administered (5 mg/kg, PO, q 12 h for 10 days) and the testing protocol repeated. Degradation changes in the detection threshold for dogs were assessed. RESULTS Metronidazole administration resulted in degradation of the detection threshold for 2 of 3 explosives (ammonium nitrate and trinitrotoluene). Nine of 18 dogs had a degradation of performance in response to 1 or more explosives (5 dogs had degradation on day 5 or 10 and 4 dogs had degradation on both days 5 and 10). There was no significant degradation during doxycycline administration. CONCLUSIONS AND CLINICAL RELEVANCE Degradation in the ability to detect odors of explosives during metronidazole administration at 25 mg/kg, PO, every 12 hours, indicated a potential risk for use of this drug in ED dogs. Additional studies will be needed to determine whether lower doses would have the same effect. Doxycycline administered at the tested dose appeared to be safe for use in ED dogs.

  11. Molecular and Proteomic Analysis of Levofloxacin and Metronidazole Resistant Helicobacter pylori.

    PubMed

    Hanafi, Aimi; Lee, Woon Ching; Loke, Mun Fai; Teh, Xinsheng; Shaari, Ain; Dinarvand, Mojdeh; Lehours, Philippe; Mégraud, Francis; Leow, Alex Hwong Ruey; Vadivelu, Jamuna; Goh, Khean Lee

    2016-01-01

    Antibiotic resistance in bacteria incurs fitness cost, but compensatory mechanisms may ameliorate the cost and sustain the resistance even under antibiotics-free conditions. The aim of this study was to determine compensatory mechanisms of antibiotic resistance in H. pylori. Five strains of levofloxacin-sensitive H. pylori were induced in vitro to develop resistance. In addition, four pairs of metronidazole-sensitive and -resistant H. pylori strains were isolated from patients carrying dual H. pylori populations that consist of both sensitive and resistant phenotypes. Growth rate, virulence and biofilm-forming ability of the sensitive and resistant strains were compared to determine effects of compensatory response. Proteome profiles of paired sensitive and resistant strains were analyzed by liquid chromatography/mass spectrophotometry (LC/MS). Although there were no significant differences in growth rate between sensitive and resistant pairs, bacterial virulence (in terms of abilities to induce apoptosis and form biofilm) differs from pair to pair. These findings demonstrate the complex and strain-specific phenotypic changes in compensation for antibiotics resistance. Compensation for in vitro induced levofloxacin resistance involving mutations of gyrA and gyrB was functionally random. Furthermore, higher protein translation and non-functional protein degradation capabilities in naturally-occuring dual population metronidazole sensitive-resistant strains may be a possible alternative mechanism underlying resistance to metronidazole without mutations in rdxA and frxA. This may explain the lack of mutations in target genes in ~10% of metronidazole resistant strains.

  12. Investigating the dissolution profiles of amoxicillin, metronidazole, and zidovudine formulations used in Trinidad and Tobago, West Indies.

    PubMed

    Stuart, Arlene Villarroel; Zuo, Jieyu; Löbenberg, Raimar

    2014-10-01

    Trinidad and Tobago is a twin-island Republic in the Caribbean and like many developing countries, it has included generic drugs on the national drug formulary to decrease the financial burden of pharmaceutical medications. However, to ensure that medications received by patients are beneficial, generic drugs need to be interchangeable with the innovator which has demonstrated safety, efficacy, and quality. The objective of the study was to compare the dissolution profiles and weight variations for different formulations of amoxicillin, metronidazole, and zidovudine that are on the national drug formulary and marketed in Trinidad and Tobago. All the products investigated are categorized as class 1 drugs according to the Biopharmaceutics Classification System (BCS) and the dissolution profiles were assessed according to the World Health Organization (WHO) criteria for interchangeability between products. The similarity factor, f 2, was used to determine sameness between the products. No generic formulation was found to be similar to Amoxil® 500-mg capsules. The two generic products for metronidazole 200-mg tablets demonstrated more than 85% drug release within 15 min in all three of the buffers; however, their 400-mg counterparts did not fulfill this requirement. The zidovudine 300-mg tablet complied with the requirements in buffer pH 4.5 and simulated gastric fluid (SGF) but not for simulated intestinal fluid (SIF). Some Class 1 pharmaceutical formulations may possess the same active ingredient and amount of drug but may show significant differences to in vitro equivalence requirements. Nevertheless, the dissolution process is suitable to detect these variations.

  13. Design and biological evaluation of novel quinolone-based metronidazole derivatives as potent Cu(2+) mediated DNA-targeting antibacterial agents.

    PubMed

    Zhang, Ling; Kumar, Kannekanti Vijaya; Geng, Rong-Xia; Zhou, Cheng-He

    2015-09-01

    A series of novel quinolone-based metronidazole derivatives as new type of antimicrobial agents were developed and characterized. Most of them gave good antibacterial activity towards the Gram-positive and negative bacteria. Noticeably, quinolone derivative 3i exhibited low MIC value of 0.25 μg/mL against Pseudomonas aeruginosa, which was even superior to reference drugs Norfloxacin, Ciprofloxacin and Clinafloxacin. The further research revealed that compound 3i could intercalate into P. aeruginosa DNA through copper ion bridge to form a steady 3i-Cu(2+)-DNA ternary complex which might further block DNA replication to exert the powerful bioactivities.

  14. Metronidazole and hydroxymetronidazole central nervous system distribution: 1. microdialysis assessment of brain extracellular fluid concentrations in patients with acute brain injury.

    PubMed

    Frasca, Denis; Dahyot-Fizelier, Claire; Adier, Christophe; Mimoz, Olivier; Debaene, Bertrand; Couet, William; Marchand, Sandrine

    2014-01-01

    The distribution of metronidazole in the central nervous system has only been described based on cerebrospinal fluid data. However, extracellular fluid (ECF) concentrations may better predict its antimicrobial effect and/or side effects. We sought to explore by microdialysis brain ECF metronidazole distribution in patients with acute brain injury. Four brain-injured patients monitored by cerebral microdialysis received 500 mg of metronidazole over 0.5 h every 8 h. Brain dialysates and blood samples were collected at steady state over 8 h. Probe recoveries were evaluated by in vivo retrodialysis in each patient for metronidazole. Metronidazole and OH-metronidazole were assayed by high-pressure liquid chromatography, and a noncompartmental pharmacokinetic analysis was performed. Probe recovery was equal to 78.8% ± 1.3% for metronidazole in patients. Unbound brain metronidazole concentration-time curves were delayed compared to unbound plasma concentration-time curves but with a mean metronidazole unbound brain/plasma AUC0-τ ratio equal to 102% ± 19% (ranging from 87 to 124%). The unbound plasma concentration-time profiles for OH-metronidazole were flat, with mean average steady-state concentrations equal to 4.0 ± 0.7 μg ml(-1). This microdialysis study describes the steady-state brain distribution of metronidazole in patients and confirms its extensive distribution.

  15. Metronidazole susceptibility testing for Helicobacter pylori: comparison of disk, broth, and agar dilution methods and their clinical relevance.

    PubMed Central

    DeCross, A J; Marshall, B J; McCallum, R W; Hoffman, S R; Barrett, L J; Guerrant, R L

    1993-01-01

    Since the methods for metronidazole susceptibility testing of Helicobacter pylori have not been standardized or validated, we compared three methods that are used to test the metronidazole susceptibilities of 25 isolates of H. pylori. Specifically, we examined the methods of Steer's replicator agar dilution, tube broth microdilution, and modified Kirby-Bauer disk diffusion. The metronidazole disk zone sizes obtained by the disk diffusion method correlated well (r = 0.74) with the MICs obtained by the agar dilution method. Afterward, the disk diffusion method was used to characterize the metronidazole susceptibilities of 44 isolates of H. pylori. Dual therapy (bismuth and metronidazole) proved to be highly effective against metronidazole-susceptible strains (81.6% eradication rate) but fared poorly against resistant strains (16.7% eradication rate; P < 0.01). Using agar dilution testing, we validated the modified Kirby-Bauer disk diffusion method for metronidazole susceptibility testing of H. pylori and conclude that it is practical, accurate, and clinically applicable. PMID:8370723

  16. Stability of cefazolin sodium and metronidazole at 8 degrees C for use as an i.v. admixture.

    PubMed

    Rivers, T E; McBride, H A; Trang, J M

    1993-01-01

    The stability of cefazolin 1 g in metronidazole 500 mg/100 mL at 8 degrees C was studied for use as an IV admixture. The commercially available injection of cefazolin sodium 1 g vial was diluted to 5 mL with 0.9% sodium chloride injection and added to metronidazole 500 mg/100 mL. Following dilution of 2 mL to 100 mL with water, 1-mL aliquots were transferred to glass vials, refrigerated at 8 degrees, and assayed for cefazolin and metronidazole concentration at 0, 1, 2, 4, 8, 12, 24, 36, 48, and 72 hours after preparation. The concentration of cefazolin and metronidazole was determined by a stability-indicating high-performance liquid chromatographic method. The range of concentration was determined to be within 5% of the 0-hour mean concentration. Over the 72-hour period, the mean concentration of cefazolin at all assay times was within 98.4 to 101.0% of the initial concentration. The mean concentration of metronidazole at each assay time was 96.9 to 104.9% of the initial concentration. Cefazolin sodium 10 mg/mL and metronidazole 5 mg/mL, prepared by adding reconstituted cefazolin to a glass bottle of metronidazole ready-to-use solution, were stable for 72 hours when stored at 8 degrees C.

  17. Waste Material of Propolis as a Film Forming Agent Intended to Modify the Metronidazole Release: Preparation and Characterization.

    PubMed

    de Toledo, Lucas de Alcântara Sica; Rosseto, Hélen Cássia; Ravani, Laura; Cortesi, Rita; Bruschi, Marcos Luciano

    2016-01-01

    Metronidazole is an antimicrobial agent utilized for the treatment of protozoa and anaerobic bacteria infections. Many times, it is necessary to modify the metronidazole release, and the development of modified release systems may be suggested. In this study, we are able to investigate the use of the residue normally thrown out from the preparation of propolis extracts (BP) as strategy to modify the metronidazole release. We prepared films containing polymeric adjuvant (gelatin or ethylcellulose) and metronidazole, by solvent casting method. Density, mechanical properties, water vapor permeability (WVP), moisture uptake capacity (MUC), thermogravimetry, differential scanning calorimetry, Fourier transform infrared spectroscopy (FT-IR), and in vitro metronidazole release were investigated. Thickness and density of the preparations indicated that the compounds were homogeneously dispersed throughout. Mechanical properties were influenced by film composition. Films containing gelatin showed higher resistance to stress while those containing ethylcellulose presented greater flexibility. The greater the adjuvant concentrations lower the resistance to rupture and the elasticity, but higher MUC and WVP of formulations. FT-IR tests suggested interactions between BP and the adjuvants. Films were capable to protect the metronidazole and changed its release profile. BP films are of great practical importance constituting a novel strategy to modify the metronidazole release.

  18. Age-Stratified Treatment Response Rates in Hospitalized Patients with Clostridium difficile Infection Treated with Metronidazole.

    PubMed

    Pham, Vy P; Luce, Andrea M; Ruppelt, Sara C; Wei, Wenjing; Aitken, Samuel L; Musick, William L; Roux, Ryan K; Garey, Kevin W

    2015-10-01

    Consensus on the optimal treatment of Clostridium difficile infection (CDI) is rapidly changing. Treatment with metronidazole has been associated with increased clinical failure rates; however, the reasons for this are unclear. The purpose of this study was to assess age-related treatment response rates in hospitalized patients with CDI treated with metronidazole. This was a retrospective, multicenter cohort study of hospitalized patients with CDI. Patients were assessed for refractory CDI, defined as persistent diarrhea after 7 days of metronidazole therapy, and stratified by age and clinical characteristics. A total of 242 individuals, aged 60 ± 18 years (Charlson comorbidity index, 3.8 ± 2.4; Horn's index, 1.7 ± 1.0) were included. One hundred twenty-eight patients (53%) had severe CDI. Seventy patients (29%) had refractory CDI, a percentage that increased from 22% to 28% and to 37% for patients aged less than 50 years, for patients from 50 to 70 years, and for patients aged >70 years, respectively (P = 0.05). In multivariate analysis, Horn's index (odds ratio [OR], 2.04; 95% confidence interval [CI], 1.50 to 2.77; P < 0.001), severe CDI (OR, 2.25; 95% CI, 1.15 to 4.41; P = 0.018), and continued use of antibiotics (OR, 2.65; 95% CI, 1.30 to 5.39; P = 0.0072) were identified as significant predictors of refractory CDI. Age was not identified as an independent risk factor for refractory CDI. Therefore, hospitalized elderly patients with CDI treated with metronidazole had increased refractory CDI rates likely due to increased underlying severity of illness, severity of CDI, and concomitant antibiotic use. These results may help identify patients that may benefit from alternative C. difficile treatments other than metronidazole.

  19. Effect of oral administration of metronidazole or prednisolone on fecal microbiota in dogs.

    PubMed

    Igarashi, Hirotaka; Maeda, Shingo; Ohno, Koichi; Horigome, Ayako; Odamaki, Toshitaka; Tsujimoto, Hajime

    2014-01-01

    Gastrointestinal microbiota have been implicated in the pathogenesis of various gastrointestinal disorders in dogs, including acute diarrhea and chronic enteropathy. Metronidazole and prednisolone are commonly prescribed for the treatment of these diseases; however, their effects on gastrointestinal microbiota have not been investigated. The objective of this study was to evaluate the effects of these drugs on the gastrointestinal microbiota of dogs. Metronidazole was administered twice daily at 12.5 mg/kg to a group of five healthy dogs, and prednisolone at 1.0 mg/kg daily to a second group of five healthy dogs for 14 days. Fecal samples were collected before and after administration (day 0 and 14), and 14 and 28 days after cessation (day 28 and 42). DNA was extracted, and the bacterial diversity and composition of each sample were determined based on 16S ribosomal RNA (rRNA) gene sequences using next-generation sequencing (Illumina MiSeq). In the group administered metronidazole, bacterial diversity indices significantly decreased at day 14, and recovered after the cessation. Principal coordinates analysis and hierarchical dendrogram construction based on unweighted and weighted UniFrac distance matrices revealed that bacterial composition was also significantly altered by metronidazole at day 14 compared with the other time points. The proportions of Bacteroidaceae, Clostridiaceae, Fusobacteriaceae, Lachnospiraceae, Ruminococcaceae, Turicibacteraceae, and Veillonellaceae decreased, while Bifidobacteriaceae, Enterobacteriaceae, Enterococcaceae, and Streptococcaceae increased at day 14 and returned to their initial proportions by day 42. Conversely, no effect of prednisolone was observed on either the bacterial diversity or composition. Reducing pathogenic bacteria such as Fusobacteria and increasing beneficial bacteria such as Bifidobacterium through the administration of metronidazole may be beneficial for promoting gastrointestinal health; however, further

  20. Development and Evaluation of Biodegradable Chitosan Films of Metronidazole and Levofloxacin for the Management of Periodontitis.

    PubMed

    Khan, Gayasuddin; Yadav, Sarita K; Patel, Ravi R; Nath, Gopal; Bansal, Monika; Mishra, Brahmeshwar

    2016-12-01

    Metronidazole (MZ) and levofloxacin (LF) are widely employed for treatment of periodontitis, but high oral dose and resistance development after long-term oral administration limit their use. The aim of this study was to alleviate shortcomings in the treatment of periodontitis by fabrication of intrapocket, biodegradable films of chitosan (CS) loaded with MZ and LF meant for inserting into periodontal pockets to treat infections. The films were developed by solvent casting technique using propylene glycol as plasticizer and glutaraldehyde as crosslinking agent. Their physical characteristics, such as drug content, surface pH, swelling index, and folding endurance, exhibited results within limit. Further, FTIR and DSC studies revealed stability of films and compatibility between drugs and excipients. SEM images of films showed the presence of free drug particles on the surface causing burst effect. In vitro release in McIlvaine buffer pH 6.6 was of sustained nature assisted by the burst effect. CS and crosslinking agent concentrations negatively affected drug release and positively affected T90 (time for releasing 90% of the drug) due to altered matrix density. In contrast, the plasticizer concentration increases membrane permeability and hence increased drug release, lowering T90. Crosslinked films demonstrated sustained release up to 7 days. The antibacterial efficacy of films was tested on Staphylococcus aureus and Escherichia coli, indicating good antibacterial activity. Clinical trials on patients proved the therapeutic efficacy of the films by a significant (p < 0.05) decrease in the clinical markers of periodontitis, i.e. gingival index, plaque index and pocket depth. Conclusively, the films of MZ and LF were successful tools for the management of periodontitis.

  1. Novel vaccine potential of Rv3131, a DosR regulon-encoded putative nitroreductase, against hyper-virulent Mycobacterium tuberculosis strain K.

    PubMed

    Kwon, Kee Woong; Kim, Woo Sik; Kim, Hongmin; Han, Seung Jung; Hahn, Mi-Young; Lee, Jong Seok; Nam, Ki Taek; Cho, Sang-Nae; Shin, Sung Jae

    2017-03-08

    Accumulating evidence indicates that latency-associated Mycobacterium tuberculosis (Mtb)-specific antigens from the dormancy survival regulator regulon (DosR) may be promising novel vaccine target antigens for the development of an improved tuberculosis vaccine. After transcriptional profiling of DosR-related genes in the hyper-virulent Beijing Mtb strain K and the reference Mtb strain H37Rv, we selected Rv3131, a hypothetical nitroreductase, as a vaccine antigen and evaluated its vaccine efficacy against Mtb K. Mtb K exhibited stable and constitutive up-regulation of rv3131 relative to Mtb H37Rv under three different growth conditions (at least 2-fold induction) including exponential growth in normal culture conditions, hypoxia, and inside macrophages. Mice immunised with Rv3131 formulated in GLA-SE, a well-defined TLR4 adjuvant, displayed enhanced Rv3131-specific IFN-γ and serum IgG2c responses along with effector/memory T cell expansion and remarkable generation of Rv3131-specific multifunctional CD4(+) T cells co-producing TNF-α, IFN-γ and IL-2 in both spleen and lung. Following challenge with Mtb K, the Rv3131/GLA-SE-immunised group exhibited a significant reduction in bacterial number and less extensive lung inflammation accompanied by the obvious persistence of Rv3131-specific multifunctional CD4(+) T cells. These results suggest that Rv3131 could be an excellent candidate for potential use in a multi-antigenic Mtb subunit vaccine, especially against Mtb Beijing strains.

  2. Novel vaccine potential of Rv3131, a DosR regulon-encoded putative nitroreductase, against hyper-virulent Mycobacterium tuberculosis strain K

    PubMed Central

    Kwon, Kee Woong; Kim, Woo Sik; Kim, Hongmin; Han, Seung Jung; Hahn, Mi-Young; Lee, Jong Seok; Nam, Ki Taek; Cho, Sang-Nae; Shin, Sung Jae

    2017-01-01

    Accumulating evidence indicates that latency-associated Mycobacterium tuberculosis (Mtb)-specific antigens from the dormancy survival regulator regulon (DosR) may be promising novel vaccine target antigens for the development of an improved tuberculosis vaccine. After transcriptional profiling of DosR-related genes in the hyper-virulent Beijing Mtb strain K and the reference Mtb strain H37Rv, we selected Rv3131, a hypothetical nitroreductase, as a vaccine antigen and evaluated its vaccine efficacy against Mtb K. Mtb K exhibited stable and constitutive up-regulation of rv3131 relative to Mtb H37Rv under three different growth conditions (at least 2-fold induction) including exponential growth in normal culture conditions, hypoxia, and inside macrophages. Mice immunised with Rv3131 formulated in GLA-SE, a well-defined TLR4 adjuvant, displayed enhanced Rv3131-specific IFN-γ and serum IgG2c responses along with effector/memory T cell expansion and remarkable generation of Rv3131-specific multifunctional CD4+ T cells co-producing TNF-α, IFN-γ and IL-2 in both spleen and lung. Following challenge with Mtb K, the Rv3131/GLA-SE-immunised group exhibited a significant reduction in bacterial number and less extensive lung inflammation accompanied by the obvious persistence of Rv3131-specific multifunctional CD4+ T cells. These results suggest that Rv3131 could be an excellent candidate for potential use in a multi-antigenic Mtb subunit vaccine, especially against Mtb Beijing strains. PMID:28272457

  3. Metronidazole resistance of Trichomonas vaginalis as a cause of treatment failure in trichomoniasis--A case report.

    PubMed

    Kulda, J; Vojtĕchovská, M; Tachezy, J; Demes, P; Kunzová, E

    1982-12-01

    Six isolates of a strain (MRP-MT) of Trichomonas vaginalis obtained from a woman before and after unsuccessful treatment with metronidazole had an appreciably lower susceptibility to metronidazole both in vitro in the aerobic tube assay and in vivo in the mouse assay than did control strains from patients cured with standard doses of the drug. Our results support recent evidence that metronidazole-resistant strains of T vaginalis do cause treatment failure. Resistance of these strains could be detected in vitro under only aerobic but not anaerobic conditions. The prevalence of metronidazole-resistant strains of T vaginalis should be kept under surveillance in order to estimate their clinical importance. The patient harbouring the resistant strain MRP-MT was finally cured with increased doses of ornidazole.

  4. Use of metronidazole as part of an empirical antibiotic regimen after incision and drainage of infections of the odontogenic spaces.

    PubMed

    Bali, Rishi; Sharma, Parveen; Gaba, Shivani

    2015-01-01

    The combination of amoxicillin/clavulanate and metronidazole is a widely-accepted empirical regimen for infections of the odontogenic spaces. Once adequate drainage has been established micro-organisms are less likely to grow and multiply, particularly anaerobes. This may obviate the need for anaerobic coverage after drainage in healthy hosts. We studied 60 patients in this randomised prospective study, the objective of which was to evaluate metronidazole as part of an empirical antibiotic regimen after drainage of infections of the odontogenic spaces. Samples of pus were sent for culture and testing for sensitivity. Amoxicillin/clavulanate and metronidazole were given to all patients. After incision and drainage the patients were randomly allocated to two groups. In the first group both antibiotics were continued, and in the second metronidazole was withdrawn. The groups were compared both clinically and microbiologically. There were no significant differences between the groups in the resolution of infection. Thirteen patients (n=6 in the 2-antimicrobial group, and n=7 in the amoxicillin/clavulanate group) showed no improvement during the 48 h postoperatively. Overall there was need to substitute another antibiotic for amoxicillin/clavulanate in only 6 cases. Six patients in the amoxicillin/clavulanate group required the addition of metronidazole after drainage. We conclude that in healthy subjects metronidazole is not necessary in the period after drainage, but its prescription should be based on assessment of clinical and laboratory markers of infection.

  5. Evaluation of the fluid uptake kinetics and drug release from gellan gum tablets containing metronidazole.

    PubMed

    Emeje, M O; Franklin-Ude, P I; Ofoefule, S I

    2010-08-01

    In this study, the fluid uptake (swelling) kinetics and disintegrant properties of gellan gum in metronidazole tablets were evaluated in both simulated gastric and intestinal fluids (SGF and SIF respectively) without enzymes. The mechanical properties as well as the disintegration and dissolution profile of the tablets were also assessed and compared with those of two standard disintegrants: maize starch and sodium starch glycolate (Primogel). Results show that, swelling was faster and higher in SIF than SGF with the minimum and maximum swelling rates of the gum being 0.365 and 6.900 mm(3)/min respectively in SGF, while the corresponding values in SIF were 0.277 and 7.600 mm(3)/min respectively. The gum was most effective as a disintegrant for metronidazole tablets at an optimum concentration of 0.2% (w/w) when incorporated extra-granularly.

  6. Entamoeba histolytica and Trichomonas vaginalis: trophozoite growth inhibition by metronidazole electro-transferred water.

    PubMed

    Heredia-Rojas, J Antonio; Torres-Flores, Antonio Cayetano; Rodríguez-De la Fuente, Abraham O; Mata-Cárdenas, Benito David; Rodríguez-Flores, Laura E; Barrón-González, María Porfiria; Torres-Pantoja, Antonio Cayetano; Alcocer-González, Juan M

    2011-01-01

    The influence of low-frequency electromagnetic (LF-EM) waves on microorganisms has been a subject of experimental investigations for more than two decades and the results are promising. In parallel, an interesting procedure known as biophysical-information-therapy or bioresonance therapy (BRT) which in principle is based on LF-EM stimulation, has emerged. BRT was discovered in the late 1980's but it is still poorly studied. This paper demonstrates that by transferring metronidazole information to water samples by an electronic amplifier (BRT device), the growth of axenically cultured trophozoites of Entamoeba histolytica and Trichomonasvaginalis is significantly inhibited, compared with those cultures treated with non and sham electro-transferred water samples. A positive control of metronidazole, a well-known cytotoxic drug against parasites, was used as a reference.

  7. Metronidazole in the treatment of cervical cancer using Cf-252 neutron brachytherapy

    SciTech Connect

    Maruyama, Y.

    1986-01-01

    Metronidazole was tested for its possible use in the Cf-252 brachytherapy of cervical cancer as a radiosensitizer and to deal with anaerobic pelvic infection. 15 patients were treated by only 14 were evaluable. All stages from stage IB-IVB were treated and complete local tumor regression was noted in all cases although it could take place very slowly. 5/14 (36%) are 1.5-3 year survivors but only among the patients with stage I-II disease. No unusual radio-enhancing action was observed but metronidazole appeared to be useful to treat the vaginal, cervix and uterine infections often associated with high stage disease and bulky, ulcerative or necrotic tumors.

  8. Common products from gamma-radiolysis and ultraviolet photolysis of metronidazole

    NASA Astrophysics Data System (ADS)

    Moore, Douglas E.; Wilkins, Brian J.

    u.v. Photolysis of metronidazole in aqueous solution at pH 7.0 results in rearrangement through an imino-ketone to an oxadiazole. These compounds were also found following γ-radiolysis of metronidazole, being about 10% of the products. Saturation of the solution with nitrous oxide caused a slight increase in the yield of imino-ketone in radiolysis. Conversely, the imino-ketone was not detected on addition of sodium formate or propan-2-ol to the radiolysis, but an increased yield of other products was observed. It is suggested that formation of the imino-ketone and oxadiazole in both photolysis and radiolysis occurs via processes which do not involve the nitro radical anion as first transient species.

  9. Metronidazole as a radiosensitizer: a preliminary report on estimation in serum and saliva

    SciTech Connect

    Karim, A.B.M.F.; Faber, D.B.; Haas, R.E.; Hoekstra, F.H.; Njo, K.H.

    1980-09-01

    Some studies indicate the clinical benefit of hypoxic radiosensitizers in patients who are undergoing radiotherapy. Serum level of sensitizers are usualy advised; however they are very demanding on the patient. Saliva level of the sensitizers may be an alternative method. This study correlated serum level of metronidazole to the saliva level in 10 patients who were undergoing radiotherapy with the sensitizer. A change to the saliva level method appears to relieve the patients.

  10. The role of Bacteroides fragilis RecQ DNA helicases in cell survival after metronidazole exposure.

    PubMed

    Paul, Lynthia; Patrick, Sheila; Nord, Carl Erik; Abratt, Valerie

    2011-06-01

    The inactivation of Bacteroides fragilis genes encoding putative RecQ helicases recQ1, recQ2 and recQ3 (ORFs BF638R_3282, BF638R_3781, BF638R_3932) was used to determine whether these proteins are involved in cell survival following metronidazole exposure. The effects of the mutations on growth, cellular morphology and DNA integrity were also evaluated. Mutations in the RecQ DNA helicases caused increased sensitivity to metronidazole, with recQ1, recQ2 and recQ3 mutants being 1.32-fold, 41.88-fold and 23.18-fold more sensitive than the wild type, respectively. There was no difference in cell growth between the recQ1 and recQ3 mutants and the wild type. However, the recQ2 mutant exhibited reduced cell growth, aberrant cell division and increased pleiomorphism, with an increase in filamentous forms and chains of cells being observed using light, fluorescence and electron microscopy. There was no spontaneous accumulation of DNA single- or double-strand breaks in the recQ mutants, as compared with the wild type, during normal cell growth in the absence of metronidazole. Bacteroides fragilis RecQ DNA helicases, therefore, enhance cell survival following metronidazole damage. The abnormal cellular phenotype and growth characteristics of recQ2 mutant cells suggest that this gene, or the downstream gene of the operon in which it occurs, may be involved in cell division.

  11. Clinical and Neuroradiological Spectrum of Metronidazole Induced Encephalopathy: Our Experience and the Review of Literature

    PubMed Central

    Panwar, Ajay; Pandit, Alak; Das, Susanta Kumar; Joshi, Bhushan

    2016-01-01

    Metronidazole is an antimicrobial agent mainly used in the treatment of several protozoal and anaerobic infections, additionally, is often used in hepatic encephalopathy and Crohn disease. Apart from peripheral neuropathy, metronidazole can also cause symptoms of central nervous system dysfunction like ataxic gait, dysarthria, seizures, and encephalopathy which may result from both short term and chronic use of this drug and is collectively termed as “metronidazole induced encephalopathy”(MIE). Neuroimaging forms the backbone in clinching the diagnosis of this uncommon entity, especially in cases where there is high index of suspicion of intoxication. Although typical sites of involvement include cerebellum, brain stem and corpus callosum, however, lesions of other sites have also been reported. Once diagnosed, resolution of findings on Magnetic Resonance Imaging (MRI) of the Brain along with clinical improvement remains the mainstay of monitoring. Here we review the key clinical features and MRI findings of MIE as reported in medical literature. We also analyze implication of use of this drug in special situations like hepatic encephalopathy and brain abscess and discuss our experience regarding this entity. PMID:27504340

  12. Development of Floating-Mucoadhesive Microsphere for Site Specific Release of Metronidazole

    PubMed Central

    Amin, Md. Lutful; Ahmed, Tajnin; Mannan, Md. Abdul

    2016-01-01

    Purpose: The purpose of this study was to develop and evaluate metronidazole loaded floating-mucoadhesive microsphere for sustained drug release at the gastric mucosa. Methods: Alginate gastroretentive microspheres containing metronidazole were prepared by ionic gelation method using sodium bicarbonate as gas forming agent, guar gum as mucoadhesive polymer, and Eudragit L100 as drug release modifier. Carbopol was used for increasing the bead strength. The microspheres were characterized by scanning electron microscopy and evaluated by means of drug entrapment efficiency, in vitro buoyancy, and swelling studies. In vitro mucoadhesion and drug release studies were carried out in order to evaluate site specific sustained drug release. Results: All formulations showed 100% buoyancy in vitro for a prolonged period of time. Amount of guar gum influenced the properties of different formulations. The formulation containing drug and guar gum at a ratio of 1:0.5 showed the best results with 76.3% drug entrapment efficiency, 61.21% mucoadhesion, and sustained drug release. Carbopol was found to increase surface smoothness of the microspheres. Conclusion: Metronidazole mucoadhesive-floating microspheres can be effectively used for sustained drug release to the gastric mucosa in treatment of upper GIT infection. PMID:27478781

  13. Increase number of mitochondrion-like organelle in symptomatic Blastocystis subtype 3 due to metronidazole treatment.

    PubMed

    Raman, Kalyani; Kumar, Suresh; Chye, Tan Tian

    2016-01-01

    Blastocystis sp., an intestinal organism is known to cause diarrhea with metronidazole regarded as the first line of treatment despite reports of its resistance. The conflicting reports of variation in drug treatment have been ascribed to subtype differences. The present study evaluated in vitro responses due to metronidazole on ST3 isolated from three symptomatic and asymptomatic patients, respectively. Symptomatic isolates were obtained from clinical patients who showed symptoms such as diarrhea and abdominal bloating. Asymptomatic isolates from a stool survey carried out in a rural area. These patients had no other pathogens other than Blastocystis. Ultrastructural studies using transmission electron microscopy (TEM) and scanning electron microscopy (SEM) revealed drug-treated ST3 from symptomatic patients were irregular and amoebic with surface showing high-convoluted folding when treated with metronidazole. These organisms had higher number of mitochondrion-like organelle (MLO) with prominent cristae. However, the drug-treated ST3 from asymptomatic persons remained spherical in shape. Asymptomatic ST3 showed increase in the size of its central body with the MLO located at the periphery.

  14. Metronidazole or Cotrimoxazole therapy is associated with a decrease in intestinal bioavailability of common antiretroviral drugs.

    PubMed

    Dossou-Yovo, Flore; Mamadou, Godefroy; Soudy, Imar Djibrine; Limas-Nzouzi, Nicolas; Miantezila, Joe; Desjeux, Jehan-François; Eto, Bruno

    2014-01-01

    Metronidazole (MTZ) and Cotrimoxazole (CTX) are used in HIV/AIDS patients eligible for antiretroviral treatment. The objective of this animal study was to determine whether pre-treatment with antibiotics affects the intestinal bioavailability of Atazanavir (ATV) and Ritonavir (RTV). After oral administration of 1 mg MTZ and CTX for 7 days, the rat colonic mucosa were analyzed for mucus thickness or placed in Ussing chambers to measure ATV and RTV net transepithelial fluxes (Jnet). 1. In control rats, the mucus thickness was 43.3±7.6 µm and 40.7±6.9 µm, in proximal and distal colon, respectively. In proximal colon, the thickness was 57.2±8.8 and 58.2±6.9 µm after MTZ and CTX, respectively whereas in distal colon, the thickness was 121.1±38.4 and 170.5±35.0 µm (P<0.05) respectively. 2. Transepithelial conductance was reduced after MTZ or CTX in the proximal and distal colon. 3. In control, net ATV secretion was observed both in proximal (-0.36±0.02 µg.hr(-1) cm(-2)) and distal colon (-0.30±0.08 µg.hr(-1) cm(-2)). After MTZ and CTX, it was increased in the proximal colon by two 2 fold and 4 fold, respectively and in the distal colon by 3 fold and 5 fold, respectively. 4. In control, there was no net active RTV transport either in proximal (+0.01±0.01 µg.hr(-1) cm(-2)) or distal colon (+0.04±0.01 µg.hr(-1) cm(-2)). After MTZ and CTX, secretion was increased 5 fold and 10 fold, respectively, in the proximal colon and two fold and 5 fold, respectively in the distal colon (p<0.001). In conclusion, after MTZ and CTX therapy, the mucus layer was enlarged, passive permeability was decreased and ATV and RTV were actively secreted by the colonic epithelium suggesting that, in rat, the intestinal bioavailability of ATV and RTV is impaired after antibiotic therapy.

  15. Metronidazole or Cotrimoxazole Therapy Is Associated with a Decrease in Intestinal Bioavailability of Common Antiretroviral Drugs

    PubMed Central

    Dossou-Yovo, Flore; Mamadou, Godefroy; Soudy, Imar Djibrine; Limas-Nzouzi, Nicolas; Miantezila, Joe; Desjeux, Jehan-François; Eto, Bruno

    2014-01-01

    Metronidazole (MTZ) and Cotrimoxazole (CTX) are used in HIV/AIDS patients eligible for antiretroviral treatment. The objective of this animal study was to determine whether pre-treatment with antibiotics affects the intestinal bioavailability of Atazanavir (ATV) and Ritonavir (RTV). After oral administration of 1 mg MTZ and CTX for 7 days, the rat colonic mucosa were analyzed for mucus thickness or placed in Ussing chambers to measure ATV and RTV net transepithelial fluxes (Jnet). 1. In control rats, the mucus thickness was 43.3±7.6 µm and 40.7±6.9 µm, in proximal and distal colon, respectively. In proximal colon, the thickness was 57.2±8.8 and 58.2±6.9 µm after MTZ and CTX, respectively whereas in distal colon, the thickness was 121.1±38.4 and 170.5±35.0 µm (P<0.05) respectively. 2. Transepithelial conductance was reduced after MTZ or CTX in the proximal and distal colon. 3. In control, net ATV secretion was observed both in proximal (−0.36±0.02 µg.hr−1 cm−2) and distal colon (−0.30±0.08 µg.hr−1 cm−2). After MTZ and CTX, it was increased in the proximal colon by two 2 fold and 4 fold, respectively and in the distal colon by 3 fold and 5 fold, respectively. 4. In control, there was no net active RTV transport either in proximal (+0.01±0.01 µg.hr−1 cm−2) or distal colon (+0.04±0.01 µg.hr−1 cm−2). After MTZ and CTX, secretion was increased 5 fold and 10 fold, respectively, in the proximal colon and two fold and 5 fold, respectively in the distal colon (p<0.001). In conclusion, after MTZ and CTX therapy, the mucus layer was enlarged, passive permeability was decreased and ATV and RTV were actively secreted by the colonic epithelium suggesting that, in rat, the intestinal bioavailability of ATV and RTV is impaired after antibiotic therapy. PMID:24587140

  16. Reinvestigation of in vivo genotoxicity studies in man. I. No induction of DNA strand breaks in peripheral lymphocytes after metronidazole therapy.

    PubMed

    Fahrig, R; Engelke, M

    1997-12-12

    Although a rodent carcinogen, metronidazole is widely used in humans for the treatment of infections with anaerobic organisms. Metronidazole is mutagenic for microorganisms, but has a mainly negative data base for mammals and humans. Therefore, metronidazole is generally considered as a non-genotoxic carcinogen. Only the results of two human in vivo studies would allow the classification of metronidazole as genotoxic carcinogen: (1) the induction of DNA strand breaks; and (2) the induction of chromosome aberrations in peripheral lymphocytes after metronidazole therapy. Because the classification of metronidazole as genotoxic carcinogen would imply enormous consequences with respect to its application, both studies were reinvestigated very thoroughly. The present report describes the reinvestigation of the induction of DNA strand breaks after metronidazole therapy. Each two probes of lymphocytes of metronidazole-treated patients (3 x 500 to 3 x 750 mg/day for 5-8 days) were examined separately for the appearance of DNA strand breaks before and after treatment. In total, 400 nuclei were examined per patient. Immediately before the first, and 30 min to 2 h after the last application, 2 x 10 ml blood per patient was sampled, transported to the laboratory at 15-20 degrees C to make DNA repair more difficult, and examined within the next 4-7 h for DNA strand breaks. At the same time, the individual metronidazole blood plasma levels were measured. In contrast to the published reports, no induction of DNA strand breaks after metronidazole therapy could be observed in the present study. As the applied doses (15,750 mg vs. 4800 mg) and the plasma level (up to 25 micrograms/ml vs. not measured) of metronidazole were much higher than in the published study, the relevance of the clearly negative result is obvious. As induction of DNA strand breaks is a frequent prerequisite for genotoxicity, metronidazole should be considered as a non-genotoxic carcinogen, and not as a

  17. [The first metronidazole-resistant Bacteroides species isolated at Marmara University Hospital: Bacteroides thetaiotaomicron].

    PubMed

    Toprak Ülger, Nurver; Sayın, Elvan; Soyad, Ad; Dane, Faysal; Söyletir, Güner

    2013-10-01

    Bacteroides species, the predominant constituents of the human intestinal microbiota can cause serious intraabdominal and postoperative wound infections and bacteremia. Moreover, these bacteria are more resistant to antimicrobial agents than the other anaerobes. The limited number of the antimicrobials, such as carbapenems, beta-lactam/beta-lactamase inhibitors and nitroimidazoles are highly effective in eliminating Bacteroides. However, a few metronidazole-resistant isolates have been reported from several countries recently. The nim genes (nim A-G) are suggested to be responsible for the majority of the metronidazole resistance. Here, we describe a metronidazole-resistant Bacteroides thetaiotaomicron isolated from a blood culture. A gram-negative obligate anaerobic rod was isolated from the postoperative 5th day blood culture of a 62-year-old male patient with adenocarcinoma of the pancreas head. The strain was identified as B.thetaiotaomicron by using a combination of conventional tests and commercially available biochemical kits. Antimicrobial susceptibility testing was performed by agar dilution method. The resistance genes were investigated by means of PCR using specific primer pairs for nim gene. The purified PCR product was sequenced and analyzed by comparison of the consensus sequences with GenBank sequences. The MIC for metronidazole was 16 mg/L. Although the strain was intermediate according the CLSI criteria, it was resistant (> 4 mg/L) according to EUCAST criteria. The isolate was nim gene positive, and nucleotide sequencing of the PCR product shared 100% similarity with nimE gene (emb |AM042593.1 |). On the other hand the isolate was susceptible to carbapenems and sulbactam-ampicillin. Following administration of ampicillin-sulbactam, the patient's fever disappeared after 24 hours. The clinical condition improved considerably and he was discharged at day 8. The patient was followed up at the medical oncology clinic; however he died due to disease

  18. Therapeutic equivalence requires pharmaceutical, pharmacokinetic, and pharmacodynamic identities: true bioequivalence of a generic product of intravenous metronidazole.

    PubMed

    Agudelo, M; Vesga, O

    2012-05-01

    Animal models of infection have been used to demonstrate the therapeutic failure of "bioequivalent" generic products, but their applicability for this purpose requires the accurate identification of those products that are truly bioequivalent. Here, we present data comparing one intravenous generic product of metronidazole with the innovator product in a neutropenic mouse thigh anaerobic infection model. Simultaneous experiments allowed comparisons (generic versus innovator) of potency and the concentration of the active pharmaceutical ingredient (API), analytical chemistry (liquid chromatography/mass spectrometry [LC/MS]), in vitro susceptibility testing, single-dose serum pharmacokinetics (PK) in infected mice, and in vivo pharmacodynamics (PD) against Bacteroides fragilis ATCC 25825 in synergy with Escherichia coli SIG-1 in the neutropenic mouse thigh anaerobic infection model. The Hill dose-response model followed by curve-fitting analysis was used to calculate and compare primary and secondary PD parameters. The generic and the innovator products were identical in terms of the concentration and potency of the API, chromatographic and spectrographic profiles, MIC and minimal bactericidal concentrations (MBC) (2.0 mg/liter), and mouse PK. We found no differences between products in bacteriostatic doses (BD) (15 to 22 mg/kg of body weight per day) or the doses needed to kill 1 log (1LKD) (21 to 29 mg/kg per day) or 2 logs (2LKD) (28 to 54 mg/kg per day) of B. fragilis under dosing schedules of every 12 h (q12h), q8h, or q6h. The area under the concentration-time curve over 24 h in the steady state divided by the MIC (AUC/MIC ratio) was the best PD index to predict the antibacterial efficacy of metronidazole (adjusted coefficient of determination [AdjR(2)] = 84.6%), and its magnitude to reach bacteriostasis in vivo (56.6 ± 5.17 h) or to kill the first (90.8 ± 9.78 h) and second (155.5 ± 22.2 h) logs was the same for both products. Animal models of infection

  19. Simultaneous determination of ranitidine and metronidazole in human plasma using high performance liquid chromatography with diode array detection.

    PubMed

    do Nascimento, Ticiano Gomes; Oliveira, Eduardo de Jesus; Macêdo, Rui Oliveira

    2005-04-01

    The development and validation of a simple method for the simultaneous determination of ranitidine and metronidazole in human plasma is described. Plasma samples (250 microL) were deproteinized by precipitation with 60% perchloric acid, centrifuged and the supernatant directly injected into the HPLC. Separation was achieved in isocratic mode with a Shimpak C(18) column and a mobile phase consisting of 10mM potassium dihydrogen phosphate pH 3.5:acetonitrile (90:10, v/v) with UV detection at 315 nm. The method showed good selectivity and sensitivity. Good and consistent recovery for metronidazole and ranitidine was obtained: 96.22+/-3.52 and 95.00+/-4.50% for ranitidine (25-1000 ng/mL) and metronidazole (60-10,000 ng/mL), respectively (n=3). With this one-step sample preparation method, both ranitidine and metronidazole could be quantified simultaneously in human plasma with good precision (R.S.D.<15%) and accuracy (bias values below 15%). The limit of quantification for ranitidine and metronidazole were 20 and 40 ng/mL plasma, respectively.

  20. Loss of Microbiota-Mediated Colonization Resistance to Clostridium difficile Infection With Oral Vancomycin Compared With Metronidazole.

    PubMed

    Lewis, Brittany B; Buffie, Charlie G; Carter, Rebecca A; Leiner, Ingrid; Toussaint, Nora C; Miller, Liza C; Gobourne, Asia; Ling, Lilan; Pamer, Eric G

    2015-11-15

    Antibiotic administration disrupts the intestinal microbiota, increasing susceptibility to pathogens such as Clostridium difficile. Metronidazole or oral vancomycin can cure C. difficile infection, and administration of these agents to prevent C. difficile infection in high-risk patients, although not sanctioned by Infectious Disease Society of America guidelines, has been considered. The relative impacts of metronidazole and vancomycin on the intestinal microbiota and colonization resistance are unknown. We investigated the effect of brief treatment with metronidazole and/or oral vancomycin on susceptibility to C. difficile, vancomycin-resistant Enterococcus, carbapenem-resistant Klebsiella pneumoniae, and Escherichia coli infection in mice. Although metronidazole resulted in transient loss of colonization resistance, oral vancomycin markedly disrupted the microbiota, leading to prolonged loss of colonization resistance to C. difficile infection and dense colonization by vancomycin-resistant Enterococcus, K. pneumoniae, and E. coli. Our results demonstrate that vancomycin, and to a lesser extent metronidazole, are associated with marked intestinal microbiota destruction and greater risk of colonization by nosocomial pathogens.

  1. Validation of a modified Kirby-Bauer disk diffusion method for metronidazole susceptibility testing of Helicobacter pylori.

    PubMed

    Midolo, P D; Turnidge, J; Lambert, J R; Bell, J M

    1995-03-01

    Triple antimicrobial therapy that includes metronidazole has been recommended as a first-line therapy for Helicobacter pylori because it has the highest eradication rates. However, resistance in H. pylori to metronidazole has been reported worldwide and its presence may reduce the efficacy of triple therapy. Various methods for testing H. pylori against metronidazole have been used including agar dilution, disk diffusion and the Etest but there has been little standardization of methods. One hundred isolates of H. pylori from different patients were tested for susceptibility to metronidazole by agar dilution, Etest and disk diffusion (5 micrograms disk). The agar dilution results confirmed the MIC susceptibility breakpoint to be < or = 8 micrograms/ml. Using this breakpoint there was close agreement (98%) between Etest and agar dilution results. For susceptible strains, MICs by E-test were generally one twofold dilution lower. Using the error-rate bounded method, agreement between disk diffusion zone diameter and MIC was 98% for agar dilution with breakpoints of > or = 12 mm and < or = 8 micrograms/ml and 100% for Etest with breakpoints of > or = 12 mm and < or = 8 micrograms/ml. The Etest discriminated better than agar dilution between susceptible and resistant strains and was simple to perform. The disk diffusion test is a reliable and cheaper alternative to the Etest with susceptibility being a zone diameter > or = 12 mm with a 5 micrograms disk. The prevalence of metronidazole resistance in this study was 40% by Etest.

  2. Preparation of novel composites based on hydrophilized and functionalized polyacrylonitrile membrane-immobilized NZVI for reductive transformation of metronidazole

    NASA Astrophysics Data System (ADS)

    Wang, Xiangyu; Liu, Peng; Ma, Jun; Liu, Huiling

    2017-02-01

    For the first time, hydrophilized and functionalized polyacrylonitrile (PAN) membrane was synthesized via two-stage process, addition of polyvinyl alcohol and in situ polymerization of acrylic acid (AA), and nano zero-valent iron (NZVI) was incorporated within modified membrane. The as-prepared PAA/PAN-NZVI (PPN) composites possessed superior reactivity for metronidazole (MNZ) with transformation ratio 2.03 and reaction rate 4.77 times higher than that by bare NZVI. Meanwhile, the enhanced stability and recyclability of PPN composites were maintained over repeated cycles. The major advantages of synthetic method lie in the remarkably increased loading and decreased agglomeration of NZVI. Moreover, with hydrophilized and functionalized synthesis processes of membrane, the potential risk of released iron ions was not a concern due to strong chelation of grafted carboxyl groups. Analyses of morphological characteristics (FE-SEM), chemical structure (FTIR), element valence and groups (XPS) of samples confirmed the successful graft of carboxylic acid groups and formation of a uniform iron nanoparticles coating onto PAN matrix. The reaction kinetics of MNZ with PPN composites were well-described by a two-parameter pseudo-first-order decay model with activation energy of 29.5 kJ/mol. The co-solutes except humic acid had a negligible effect on MNZ transformation. Determination of intermediates revealed that nitro reduction, N-denitration and hydroxyethyl cleavage were the main pathways for transformation of MNZ. The findings suggest that the novel composites possess huge potential for antibiotics wastewater treatment.

  3. Effect of Metronidazole in Infants with Bowel Habit Change: Irrelative to the Clostridium difficile Colonization

    PubMed Central

    Kim, Eun Jin; Lee, Sung Hyun; Tchah, Hann

    2017-01-01

    Purpose Clinical symptoms associated with Clostridium difficile infection (CDI) can vary widely. Carrier state without apparent symptoms is relatively common during infancy. The objective of this study was to determine the association of C. difficile colonization with bowel habit change and the effect of C. difficile colonization treatment on restoration of normal bowel habit. Methods Between 2006 and 2014, infants at 1 to 12 months of age with diarrhea for more than 2 weeks who did not improve with conservative care were recruited from Gachon University Gil Medical Center. Infants who were followed up for at least 7 days were included. The presence or absence of C. difficile colonization, effect of metronidazole, and other medical records were reviewed. To determine the association between CDI and bowel habit change, logistic regression analysis was used. Results Of a total of 126 infants, 74 (58.7%) were male patients. Of the 126 patients, 27 (21.4%) had C. difficile colonization. Significant (p<0.05) risk factors for C. difficile colonization included artificial milk feeding (odds ratio [OR], 4.310; 95% confidence interval [CI], 1.564-11.878), prior rotavirus vaccination (OR, 4.322; 95% CI, 1.018-18.349), and antibiotic use (OR, 4.798; 95% CI, 1.430-16.101). There was improvement in bowel habit after metronidazole therapy (OR, 0.34; 95% CI, 0.15-0.79; p<0.05), regardless of the presence or absence of C. difficile colonization. Conclusion There was no significant correlation between bowel habit change and C. difficile colonization during infancy. However, metronidazole can be used as an optional method to manage functional gastrointestinal disorders.

  4. Human pharmacokinetics and toxicity of high-dose metronidazole administered orally and intravenously

    SciTech Connect

    Urtasun, R.C.; Rabin, H.R.; Partington, J.

    1983-01-01

    This study is part of a clinical program to assess the use of nitroimidazoles as radiosensitizers of hypoxic tumor cells. A total of 37 patients with malignant tumors have been entered into the study to receive oral high-dose metronidazole in conjunction with radiation. Twenty-eight patients with malignant brain tumors received 6 gm/m2 three times a week for 3 weeks (a mean total dose of 5.3 gm/m2). Maximum mean plasma drug concentration of 1 mM was obtained at 4 hours after drug ingestion with a mean half-life of 13 hours. Tissue and cerebrospinal fluid levels of 80% to 90% of the plasma levels were obtained at 4 to 6 hours. A linear relationship between increased drug dose and increased plasma concentration was observed at doses of 2.5 gm/m2 up to 6 gm/m2. Acute gastrointestinal and central nervous system toxicity was the dose-limiting factor (50% and 25%, respectively, at total doses of 5.3 gm/m2). Pharmacokinetic studies of intravenous metronidazole were performed in eight consenting patients. Single doses of 0.5, 1, 1.5, and 2 gm were administered intravenously by zero-order infusion pump. Seven of the eight patients received a second identical dose orally 1 week later and the results were compared. Open two-compartment kinetic characteristics of metronidazole were computed from simultaneous plasma infusion and urine excretion rate equations, by use of a nonlinear least-squares regression analysis program (NONLIN). The mean (+/- SD) for alpha half-life was 1.2 +/- 1.3 hours, and that for the beta half-life was 9.8 +/- 5.9 hours. The absolute oral bioavailability was estimated to approximate 100%.

  5. Comparative antimicrobial efficacy of Metapex, Metronidazole, BioPure MTAD, Aztreonam on Bacteroides fragilis and Propionibacterium acne

    PubMed Central

    Balakrishnan, Rajkumar; Dubey, Sandeep; Dhole, Tapan Kumar N; Boruah, Lalit C; Srivastava, Sanjeev

    2013-01-01

    Aim: The purpose of this study was to evaluate the comparative antibacterial efficacy of Biopure MTAD, Metapex, Metronidazole, and Aztreonam against two obligate anerobic bacteria. Materials and Methods: Antimicrobial efficacy of selected medicaments against two obligate anaerobic bacteria Bacteroides fragilis and Propionibacterium acnes was done by Agar disc-diffusion method. Pre-sterilized Whatman paper discs, 6 mm in diameter and soaked with the test solution, were prepared and placed onto the previously seeded agar Petri plates. Each plate was incubated in anaerobic jar for anerobic environment at 37°C for 48 hours. A zone of inhibition was recorded for each plate and the results were analysed statistically. Saline and ethanol used as control group in this study. Results: Biopure MTAD, Metapex and Metronidazole were effective against all the selected microorganisms. Aztreonam was effective against Bacteroides fragilis. Saline and ethanol used as control were ineffective. Conclusions: Metronidazole showed the superior antibacterial property amongst the tested medicaments. PMID:23956535

  6. Isolation of Clostridium difficile from dogs with digestive disorders, including stable metronidazole-resistant strains.

    PubMed

    Orden, Cristina; Blanco, Jose L; Álvarez-Pérez, Sergio; Garcia-Sancho, Mercedes; Rodriguez-Franco, Fernando; Sainz, Angel; Villaescusa, Alejandra; Harmanus, Celine; Kuijper, Ed; Garcia, Marta E

    2017-02-01

    The prevalence of Clostridium difficile in 107 dogs with diverse digestive disorders attended in a Spanish veterinary teaching hospital was assessed. The microorganism was isolated from 13 dogs (12.1%) of different disease groups. Isolates belonged to PCR ribotypes 078, 106, 154 and 430 (all of them toxigenic) and 110 (non-toxigenic), and were resistant to several antimicrobial drugs. Notably, seven isolates obtained from different dogs displayed stable resistance to metronidazole. The results of this study provide further evidence that dogs can act as a reservoir of C. difficile strains of epidemic ribotypes with resistance to multiple antibiotics.

  7. Pharmacokinetics of metronidazole in foals: influence of age within the neonatal period.

    PubMed

    Swain, E A; Magdesian, K G; Kass, P H; Edman, J E; Knych, H K

    2015-06-01

    Neonatal foals have unique pharmacokinetics, which may lead to accumulation of certain drugs when adult horse dosage regimens are used. Given its lipophilic nature and requirement for hepatic metabolism, metronidazole may be one of these drugs. The purpose of this study was to determine the pharmacokinetic profiles of metronidazole in twelve healthy foals at 1-2.5 days of age when administered as a single intravenous (IV) and intragastric (IG) dose of 15 mg/kg. Foals in the intravenous group were studied a second time at 10-12 days of age to evaluate the influence of age on pharmacokinetics within the neonatal period. Blood samples were collected at serial time points after metronidazole administration. Metronidazole concentration in plasma was measured using LC-MS. Pharmacokinetic parameters were determined using noncompartmental analysis and compared between age groups. At 1-2.5 days of age, the mean peak plasma concentration after IV infusion was 18.79 ± 1.46 μg/mL, elimination half-life was 11.8 ± 1.77 h, clearance was 0.84 ± 0.13 mL/min/kg and the volume of distribution (steady-state) was 0.87 ± 0.07 L/kg. At 10-12 days of age, the mean peak plasma concentration after IV infusion was 18.17 ± 1.42 μg/mL, elimination half-life was 9.07 ± 2.84 h, clearance was 1.14 ± 0.21 mL/min/kg and the volume of distribution (steady-state) was 0.88 ± 0.06 L/kg. Oral approximated bioavailability was 100%. Cmax and Tmax after oral dosing were 14.85 ± 0.54 μg/mL and 1.75 (1-4) h, respectively. The elimination half-life was longer and clearance was reduced in neonatal foals at 1-2.5 days as compared to 10-12 days of age (P = 0.006, P = 0.001, respectively). This study warrants consideration for altered dosing recommendations in foals, especially a longer interval (12 h).

  8. [Pneumatosis Coli Treated with Metronidazole and Hyperbaric Oxygen Therapy: A Successful Case].

    PubMed

    Costa, Mariana; Morgado, Carolina; Andrade, David; Guerreiro, Francisco; Coimbra, João

    2015-01-01

    Pneumatosis intestinalis, characterized by the presence of gas within the bowel wall, is an uncommon condition with variable presentation. It may be idiopathic or secondary to other diseases. A computed tomography scan is the most sensitive method for diagnosis. In the absence of signs and symptoms of complications, such as perforation and peritonitis, pneumatosis intestinalis can be managed conservatively. We present the case of a 59-year-old woman with pneumatosis coli secondary to benign ovary teratoma. After surgery she remained symptomatic and was successfully treated with metronidazole and hyperbaric oxygen therapy.

  9. Standardization of disk diffusion test and its clinical significance for susceptibility testing of metronidazole against Helicobacter pylori.

    PubMed Central

    Xia, H; Keane, C T; Beattie, S; O'Morain, C A

    1994-01-01

    Susceptibilities of 121 clinical Helicobacter pylori strains to metronidazole were determined by both a 5-micrograms metronidazole disk diffusion test and a plate dilution method in duplicate and after different periods of incubation. The distribution of MICs of metronidazole against H. pylori among the strains was found to be bimodal. The diameters of inhibitory zones obtained by the disk diffusion test and the MICs obtained by the plate dilution method correlated well, especially after 4 days of incubation (r = 0.77). An inhibitory zone diameter of 20 mm was found to correspond to a MIC of 8 micrograms/ml and is recommended as a suitable zone for differentiating susceptibility and resistance with a 5-micrograms metronidazole disk. Three interpretive categories of susceptibility results were defined; strains with inhibitory zone diameters of more than 26 mm were defined as susceptible (MIC, < 4 micrograms/ml), strains with zone diameters of 20 to 26 mm were deemed intermediate (MIC, 4 to 8 micrograms/ml), and those with zone diameters of less than 20 mm were deemed resistant (MIC, > 8 micrograms/ml). Furthermore, 76 H. pylori-positive patients with duodenal ulcers or nonulcer dyspepsia were treated with a 1 week of triple therapy (colloidal bismuth subcitrate, metronidazole, and tetracycline). H. pylori strains were isolated before treatment from antral biopsies from those patients, and the metronidazole susceptibilities of the strains were determined by the disk diffusion test. H. pylori status was evaluated again 4 weeks after completion of treatment. The eradication rates for susceptible, intermediate, and resistant strains were 95.9% (47 of 49), 62.5% (5 of 8), and 52.6% (10 of 19), respectively. It is included that the 5-micrograms disk diffusion test is easy to perform and gives final results similar to those of the plate dilution method. The three interpretive categories of susceptibility may be of benefit for clinical choice of chemotherapy in eradicating

  10. Preparation and evaluation of gastroretentive floating pellets of metronidazole using Na-alginate and hydroxyl propyl methyl cellulose polymers.

    PubMed

    Biswas, S K; Paul, S; Chowdhury, A; Das, J

    2012-03-15

    Gastroretentive floating pellets of metronidazole were formulated to prolong the gastric residence time in order to obtain controlled release characteristics of the drug. Nine formulations of metronidazole floating pellets such as AX, BX, CX, AY, BY, CY, AZ, BZ and CZ were prepared by extrusion method using different quantities of hydroxyl propyl methyl cellulose (HPMC) polymers such as methocel K4M premium and methocel K100LV premium in the ratio of 2:1, 1:2 and 1.5:1.5 while the amount of Na-alginate used in the formulations was 3.50, 5.25 and 7.0 g, respectively. The in vitro dissolution studies were carried out in 900 mL of phosphate buffer (pH 1.2) at 37 +/- 0.5 degrees C and 50 rpm for 6 h using USP XXIV paddle method and the content of drug release was done by UV spectrophotometer at 277 nm. It was found that the percent release of metronidazole from different formulations was different with passing of time. The drug release profile of the formulation (AX) having Na-alginate 3.50 g methocel K4M premium and methocel K100LV premium in the ratio of 2:1 showed best fit to Higuchi release kinetics with R2 value of 0.994. Finally, it might be concluded that the polymers had significant effect on drug release kinetics of metronidazole from floating pellets. The selection and use of suitable polymers in appropriate ratio might be very important in designing floating pellets and using the capabilities of these polymers, suitable floating pellets of metronidazole with desirable release rate could be formulated. Thus, in vivo research studies by the future researchers will confirm the appropriateness of these formulated metronidazole floating pellets.

  11. A Meta-analysis of the Effectiveness of Albendazole Compared with Metronidazole as Treatments for Infections with Giardia duodenalis

    PubMed Central

    Solaymani-Mohammadi, Shahram; Genkinger, Jeanine M.; Loffredo, Christopher A.; Singer, Steven M.

    2010-01-01

    Background Metronidazole is the most commonly used drug for the treatment of giardiasis in humans. In spite of its therapeutic efficacy for giardiasis, low patient compliance, especially in children, side effects, and the emergence of metronidazole-resistant strains may restrict its use. Albendazole has been used to treat Giardia duodenalis infections in recent years. However, efficacy studies in vivo and in vitro have produced diverse results as to its effectiveness. A moderately benign side effect profile, combined with established efficacy against many helminths, renders it promising for treatment of giardiasis in humans. Methodology and Principal Findings We performed a search in the PubMed, Scopus, EMBASE, the ISI Web of Science, LILIACS, and Cochrane Controlled Trials Register for trials published before February 2010 as well as in references of relevant research and review articles. Eight randomized clinical trials (including 900 patients) comparing the effectiveness of albendazole with that of metronidazole were included in meta-analysis. After extracting and validating the data, the pooled risk ratio (RR) was calculated using an inverse-variance random-effects model. Albendazole was found to be equally as effective as metronidazole in the treatment of giardiasis in humans (RR 0.97; 95% CI, 0.93, 1.01). In addition, safety analysis suggested that patients treated with albendazole had a lower risk of adverse effects compared with those who received metronidazole (RR 0.36; 95% CI, 0.10, 1.34), but limitations of the sample size precluded a definite conclusion. Conclusions/Significance The effectiveness of albendazole, when given as a single dose of 400 mg/day for 5 days, was comparable to that of metronidazole. Patients treated with albendazole tended to have fewer side effects compared with those who took metronidazole. Given the safety, effectiveness, and low costs of albendazole, this drug could be potentially used as an alternative and/or a replacement

  12. Metronidazole loaded carboxymethyl tamarind kernel polysaccharide-polyvinyl alcohol cryogels: preparation and characterization.

    PubMed

    Meenakshi; Ahuja, Munish

    2015-01-01

    The purpose of present study was to prepare composite hydrogels of carboxymethyl tamarind kernel polysaccharide and polyvinyl alcohol employing freeze thaw-treatment and evaluate them for release behavior. The effect of concentrations of carboxymethyl tamarind kernel polysaccharide, polyvinyl alcohol, and freeze-thaw cycles on the % release of metronidazole was studied employing central composite experimental design. The result of the study revealed that the concentration of carboxymethyl tamarind kernel polysaccharide and interaction effect of concentrations of carboxymethyl tamarind kernel polysaccharide and polyvinyl alcohol influenced the release of metronidazole significantly. The optimal calculated parameters were concentration of carboxymethyl tamarind kernel polysaccharide-6.0% (w/v), concentration of polyvinyl alcohol-8.53% (w/v) and freeze-thaw cycles-4, which provided cryogels with a release of 75.77% over a period of 6h. The formation of cryogels was confirmed by Fourier-transformed infrared spectroscopy and X-ray diffraction studies. Thermal studies revealed higher thermal stability of cryogel.

  13. Effect of serum albumin presence on the binding constant of metronidazole to the phospholipid membranes fluorescence study

    NASA Astrophysics Data System (ADS)

    Sułkowska, A.

    1999-05-01

    The experiment was designed to test the possibility of entrapping the drug metronidazole into liposome vesicles in order to use liposome vesicles as a drug carrier. We estimated the effect of size of the liposome and the presence of serum albumin on the leakage of the drug. Some interactions between the lipid membrane surface and serum albumin were demonstrated. As the effects of lipid composition and physical states in membranes on protein adsorption and binding are poorly understood, it is difficult to estimate the protein interaction with the lipid membrane surface. The fluorescence quenching technique was used in this investigation. The fluorescence of serum albumin tryptophanyl residues is reduced by the presence of metronidazole. When incorporated into liposomes, metronidazole reduces the fluorescence of tryptophanyl residues of BSA to a lesser extent. The least effect of metronidazole on the fluorescence of albumin is shown when the drug is incorporated into large liposomes (450 nm). Larger liposomes are less susceptible to the presence of serum albumin than the smaller ones. Large size of the liposomes is necessary to retain their stability in plasma.

  14. Metronidazole Injection

    MedlinePlus

    ... gynecologic, and abdominal (stomach area) infections caused by bacteria. It is also used to treat endocarditis (infection ... of medications called antibacterials. It works by killing bacteria and protozoa that cause infection.Antibiotics such as ...

  15. A meta-analysis of metronidazole and vancomycin for the treatment of Clostridium difficile infection, stratified by disease severity.

    PubMed

    Di, Xiuzhen; Bai, Nan; Zhang, Xin; Liu, Bin; Ni, Wentao; Wang, Jin; Wang, Kai; Liang, Beibei; Liu, Youning; Wang, Rui

    2015-01-01

    The aim of this meta-analysis was to compare the efficacy of metronidazole and vancomycin for the treatment of Clostridium difficile infection, especially to investigate which agent was superior for treating either mild or severe C. difficile infection. A meta-analysis of randomized controlled trials and cohort studies identified in Pubmed, Embase, and the Cochrane Library was conducted. Four randomized controlled trials and two cohort studies involving 1218 patients were included in this meta-analysis. Metronidazole was inferior to vancomycin for treating C. difficile infection in terms of both initial clinical cure rates (risk ratio, RR=0.91, 95% confidence interval, CI=0.84-0.98, p=0.02) and sustained cure rates (RR=0.88, 95% CI=0.82-0.96, p=0.003). For mild C. difficile infection, the efficacy of metronidazole and vancomycin resulted in similar clinical cure rates (RR=0.94, 95% CI=0.84-1.04, p=0.21) and sustained cure rates (RR=0.93, 95% CI=0.83-1.05, p=0.26). For severe C. difficile infection the efficacy of vancomycin was superior to metronidazole in terms of clinical cure rates (RR=0.81, 95% CI=0.69-0.95, p=0.009), whereas sustained cure rates were similar (RR=0.86, 95% CI=0.72-1.02, p=0.08). Regarding microbiological cure metronidazole therapy was as effective as vancomycin therapy (RR=0.88, 95% CI=0.64-1.21, p=0.43). Recurrence rates with metronidazole and vancomycin for both mild C. difficile infection (RR=0.95, 95% CI=0.56-1.60, p=0.85) and severe C. difficile infection (RR=1.27, 95% CI=0.85-1.91, p=0.25) were not different. Likewise, no difference in all-cause mortality was found as well (RR=0.87, 95% CI=0.56-1.35, p=0.53). In conclusion, vancomycin provides improved initial clinical and sustained cure rates in patients with C. difficile infection compared with metronidazole, especially in patients with severe C. difficile infection. In view of these data, vancomycin may be considered first line therapy for severe C. difficile infection.

  16. High rate of non-susceptibility to metronidazole and clindamycin in anaerobic isolates: Data from a clinical laboratory from Karachi, Pakistan.

    PubMed

    Sheikh, Sadia Omer; Jabeen, Kauser; Qaiser, Saba; Ahsan, Syed Tanwir; Khan, Erum; Zafar, Afia

    2015-06-01

    Due to increasing resistance amongst anaerobic pathogens periodic surveillance of resistance has been recommended in regional/local settings. Anaerobic antimicrobial susceptibility testing is not routinely performed in many laboratories in Pakistan, hence absence of local data may lead to inappropriate empirical therapy in serious cases. 121 clinically significant anaerobic strains (26/121; 21% bacteremic isolates) were isolated and saved from 2010 to 2011. Susceptibility testing against metronidazole, clindamycin, co-amoxiclav, meropenem, piperacillin/tazobactam, linezolid and gatifloxacin was performed by determining minimum inhibitory concentrations (MICs). A high proportion of non-susceptible strains to metronidazole (10% of 121 isolates) and clindamycin (12% of 121 isolates) was seen, most noticeable in Bacteroides fragilis. Three Bacteroides species strains were non-susceptible to both metronidazole and clindamycin. One strain of Clostridium species was fully resistant to metronidazole and had intermediate resistance to clindamycin. No resistance to any of the other tested antibiotics was seen. Resistance to metronidazole was higher in bacteremic vs. non bacteremic isolates (p = value 0.07). In our setting where there is a high usage of empirical metronidazole and clindamycin for the treatment of serious anaerobic infections clinicians should be aware of increased resistance to these agents. Periodic surveillance of resistance to anti-anaerobic drugs especially metronidazole and clindamycin should be performed to generate antibiogram and guide appropriate empiric therapy.

  17. High-dose metronidazole: pharmacokinetics and bioavailability using an iv preparation and application of its use as a radiosensitizer

    SciTech Connect

    Rabin, H.R.; Urtasun, R.C.; Partington, J.; Koziol, D.; Sharon, M.; Walker, K.

    1980-10-01

    As an extension of studies on the clinical use of nitroimidazoles as radiosensitizers, single-dose pharmacokinetic studies of iv metronidazole (500 mg/100-ml vials) were performed in eight consenting patients. Single doses of 0.5, 1.0, 1.5, and 2.0 g (0.29 to 1.21 g/m2) were administered iv by a zero-order infusion pump. Serial timed blood and urine samples were assayed for metronidazole and its two metabolites (acetic acid and ethoxy compounds) using a high-pressure liquid chromatographic assay. Open two-compartment kinetic characteristics of metronidazole were computed from simultaneous plasma infusion and urine excretion-rate equations using a nonlinear least-squares regression analysis program (NONLIN). Means of the four kinetic parameters were (h-1): k12, 1.18; k21, 0.86; k10, 0.22; and k'e, 0.46 x 10(-4). Means of the apparent volumes of distribution were (liters/kg): Vc, 0.41; VB, 1.02; and Vss, 0.75. The mean (+- SD) for alpha-half-life was 1.2 +- 1.3 hours, and that for beta-half-life was 9.8 +- 5.9 hours. Seven of the eight patients received a second identical dose orally 1 week later, and the absolute bioavailability was estimated to approximate 100%. Unless the oral route is not feasible and if immediate high peak blood levels are not necessary, oral metronidazole is the preferred route of administration of metronidazole for its radiosensitizing effects.

  18. Efficacy of the treatment of dogs with leishmaniosis with a combination of metronidazole and spiramycin.

    PubMed

    Pennisi, M G; De Majo, M; Masucci, M; Britti, D; Vitale, F; Del Maso, R

    2005-03-12

    Twenty-seven dogs infected naturally with Leishmania infantum were used in a randomised controlled trial to compare the clinical and parasitological efficacy of an oral treatment with a combination of metronidazole and spiramycin (13 dogs) with the efficacy of conventional treatment with meglumine antimonate and allopurinol (14 dogs) as controls. In the test group one dog had to be withdrawn from the treatment because it developed pemphigus foliaceus; 10 of the dogs were clinically responsive but none was cured parasitologically. In the control group four dogs were withdrawn from the treatment because of side effects; eight of the dogs were clinically responsive but none was cured parasitologically. The control group showed signs of improvement after an average of 30 days, whereas the test group did not show signs of improvement until after an average of 45 days.

  19. Detection of metronidazole and ronidazole from environmental samples by surface enhanced Raman spectroscopy.

    PubMed

    Han, Caiqin; Chen, Jing; Wu, Xiaomeng; Huang, Yao-Wen; Zhao, Yiping

    2014-10-01

    In this study, the surface enhanced Raman spectra (SERS) of two prohibited veterinary drugs, metronidazole (MNZ) and ronidazole (RNZ), have been acquired, and compared to the theoretically calculated spectra using density function theory (DFT). The experimental Raman and SERS spectra of MNZ and RNZ exhibit high resemblance with the DFT calculations. SERS detection of MNZ and RNZ from standard solutions as well as real environmental samples (tap, lake, swamp waters and soil) was performed on highly sensitive and reproducible silver nanorod array substrates. The limits of detection for MNZ and RNZ are 10 and 1 µg/mL in methanol and ultra-pure water, respectively, and 10-50 µg/mL in the environmental samples. The SERS-based method demonstrates its potential as a rapid, simple, and inexpensive means for the onsite screening of banned antibiotics from the aquatic and sediment environments, with minimal requirement for sample pretreatment.

  20. EVALUATION OF THE MUTAGENIC ACTIVITY OF 3-NBA (3-NITROABENZANTHRONE) USING STRAINS OF SALMONELLA TYPHIMURIUM WITH DIFFERENT LEVELS OF THE ENZYMES NITROREDUCTASE AND ACETYLTRANSFERASE

    EPA Science Inventory

    The 3-NBA (3-nitro-7H- benz[d,e]antracen-7-one) is extremely potent in the Ames test an useful test for mutagenicity, being a possible inducer of tumors in animals and possible carcinogen for human beings. 3-NBA was previously identified in the exhausts of diesel, particulate mat...

  1. Effect of metronidazole versus standard care on length of stay of patients admitted with severe infectious mononucleosis: a randomized controlled trial.

    PubMed

    Lennon, P; O'Neill, J P; Fenton, J E

    2014-07-01

    Metronidazole may be of use in the treatment of infectious mononucleosis (IM). Our aim is to show that metronidazole shortens hospital stay for patients with severe IM. A single-centre randomized controlled trial was undertaken in patients admitted with severe IM, who were with a similar group treated by the standard care. Patients were blinded to which treatment arm they were in. Forty-two of these patients were enrolled in the trial. The primary endpoint was the difference in length of stay. This was significantly less in the metronidazole group (3.67 days v 4.67) (p 0.032). This study demonstrates that metronidazole has a role to play in severe infectious mononucleosis.

  2. Multicenter, double-blind, randomized, phase II trial to assess the safety and efficacy of ceftolozane-tazobactam plus metronidazole compared with meropenem in adult patients with complicated intra-abdominal infections.

    PubMed

    Lucasti, Christopher; Hershberger, Ellie; Miller, Benjamin; Yankelev, Sara; Steenbergen, Judith; Friedland, Ian; Solomkin, Joseph

    2014-09-01

    Ceftolozane-tazobactam (TOL-TAZ) is a novel antibacterial with activity against Pseudomonas aeruginosa and other common Gram-negative pathogens, including extended-spectrum β-lactamase (ESBL)-producing Enterobacteriaceae, that are associated with complicated intra-abdominal infections (cIAIs). This prospective, double-blind, randomized, multicenter, phase II trial assessed patient clinical and microbiological responses to and the safety of TOL-TAZ plus metronidazole compared with those of meropenem. Hospitalized adults with cIAIs that required surgical intervention were randomized (2:1) to receive intravenous (i.v.) TOL-TAZ (1.5 g [containing 1,000 mg TOL and 500 mg TAZ] every 8 h [q8h]) with or without i.v. metronidazole (500 mg q8h) or i.v. meropenem (1 g q8h) for 4 to 7 days. The primary endpoint was the clinical response at the test-of-cure visit in the microbiologically modified intent-to-treat (mMITT) and microbiologically evaluable (ME) populations. Secondary measures included the patients' microbiological response and safety. In total, 82 patients received TOL-TAZ (90.2% with metronidazole), and 39 received meropenem. For the mMITT population, clinical cure was seen in 83.6% of the patients (51/61; 95% confidence interval [CI], 71.9 to 91.8) who received TOL-TAZ and 96.0% of the patients (24/25; 95% CI, 79.6 to 99.9) who received meropenem (difference, -12.4%; 95% CI, -34.9% to 11.1%); in the ME population, clinical cure was seen in 88.7% and 95.8% of the patients (difference, -7.1%; 95% CI, -30.7% to 16.9%) who received TOL-TAZ and meropenem, respectively. TOL-TAZ demonstrated microbiological success against Escherichia coli (89.5%), Klebsiella pneumoniae (100%), and P. aeruginosa (100%). The adverse event rates were similar in the groups (50.0% with TOL-TAZ and 48.8% with meropenem). TOL-TAZ in combination with metronidazole was well tolerated and resulted in clinical and microbiological success rates supportive of further clinical development in

  3. Comparison of the Effects of Myrtus Communis L, Berberis Vulgaris and Metronidazole Vaginal Gel alone for the Treatment of Bacterial Vaginosis

    PubMed Central

    Masoudi, Mansoureh; Rafieian-Kopaei, Mahmoud

    2016-01-01

    Introduction There is a growing tendency towards herbal medicines for treatment of vaginitis. Antibacterial and antifungal effects of Myrtus communis L and Berberis vulgaris have been demonstrated invitro and invivo. Aim This study aimed to compare the therapeutic effects of the vaginal gel of Berberis vulgaris 5% (in metronidazole base) and Myrtus communis L 2% (in metronidazole base) with only metronidazole vaginal gel 0.75% on bacterial vaginosis. Materials and Methods This study was a randomized clinical trial research on 120 married women aged 18-40 years affected by bacterial vaginosis attended for treatment to gynaecology clinic of Hajar Hospital (Shahrekord, Iran). They were randomly divided into three groups of 40 participants. Diagnostic criteria were Amsel’s criteria. Myrtus communis L, Berberis vulgaris vaginal gel or metronidazole vaginal gel for five-night usage were prescribed to each group, and after 7 days therapeutic effects were assessed. Data analysis was performed using ANOVA and Chi-square tests. Results A statistically significant difference was observed with regard to treatment response among the study groups (p<0.001), with Myrtus communis L and Berberis vulgaris groups having a better response than metronidazole gel alone. Moreover, there was no significant difference between Myrtus communis L and Berberis vulgaris groups (p= 0.18). The patients in groups of Myrtus communis L or Berberis vulgaris in metronidazole base did not experience any relapse, but in metronidazole group, 30% of patients experienced relapse during three weeks follow up. Conclusion Findings of the study showed that treatment with a combination of Myrtus communis L or Berberis vulgaris in metronidazole base improve the efficacy of bacterial vaginosis therapy. PMID:27134945

  4. Significant reduction of brain cysts caused by Toxoplasma gondii after treatment with spiramycin coadministered with metronidazole in a mouse model of chronic toxoplasmosis.

    PubMed

    Chew, Wai Kit; Segarra, Ignacio; Ambu, Stephen; Mak, Joon Wah

    2012-04-01

    Toxoplasma gondii is a parasite that generates latent cysts in the brain; reactivation of these cysts may lead to fatal toxoplasmic encephalitis, for which treatment remains unsuccessful. We assessed spiramycin pharmacokinetics coadministered with metronidazole, the eradication of brain cysts and the in vitro reactivation. Male BALB/c mice were fed 1,000 tachyzoites orally to develop chronic toxoplasmosis. Four weeks later, infected mice underwent different treatments: (i) infected untreated mice (n = 9), which received vehicle only; (ii) a spiramycin-only group (n = 9), 400 mg/kg daily for 7 days; (iii) a metronidazole-only group (n = 9), 500 mg/kg daily for 7 days; and (iv) a combination group (n = 9), which received both spiramycin (400 mg/kg) and metronidazole (500 mg/kg) daily for 7 days. An uninfected control group (n = 10) was administered vehicle only. After treatment, the brain cysts were counted, brain homogenates were cultured in confluent Vero cells, and cysts and tachyzoites were counted after 1 week. Separately, pharmacokinetic profiles (plasma and brain) were assessed after a single dose of spiramycin (400 mg/kg), metronidazole (500 mg/kg), or both. Metronidazole treatment increased the brain spiramycin area under the concentration-time curve from 0 h to ∞ (AUC(0-∞)) by 67% without affecting its plasma disposition. Metronidazole plasma and brain AUC(0-∞) values were reduced 9 and 62%, respectively, after spiramycin coadministration. Enhanced spiramycin brain exposure after coadministration reduced brain cysts 15-fold (79 ± 23 for the combination treatment versus 1,198 ± 153 for the untreated control group [P < 0.05]) and 10-fold versus the spiramycin-only group (768 ± 125). Metronidazole alone showed no effect (1,028 ± 149). Tachyzoites were absent in the brain. Spiramycin reduced in vitro reactivation. Metronidazole increased spiramycin brain penetration, causing a significant reduction of T. gondii brain cysts, with potential clinical

  5. [Clinical Characteristics of Metronidazole-induced Encephalopathy: A Report of Two Cases and a Review of 32 Japanese Cases in the Literature].

    PubMed

    Kato, Hideaki; Sosa, Hiroko; Mori, Masaaki; Kaneko, Takeshi

    2015-09-01

    Metronidazole is an antibiotic classically used against most anaerobic bacteria and protozoa. Because an intravenous form of metronidazole has recently entered the market, the use of this antibiotic is attracting renewed interest in many clinical settings in Japan. However, neurotoxicity is a major adverse event: in the central nervous system metronidazole-induced encephalopathy is a rare but serious condition. We performed a literature review of 34 cases including 2 of our cases, 25 from domestic conference abstracts, and 7 cases presented in full research papers. The mean patient age was 64.7 years. The conditions most commonly treated with metronidazole were brain abscess (35.3%), liver abscess (17.6%), and Clostridium difficile infection (14.7%). The most common predisposing conditions were liver dysfunction (26.5%), diabetes and other metabolic disorders (20.6%), and hematologic or solid organ malignancy (14.7%). The mean period of administration before the onset of encephalopathy symptoms was 61.3 days, and the mean total dose was 95.9g. The initial chief complaints were dysarthria (in 70.6% of the cases) and ataxia (61.8%); 82.4% of the cases were diagnosed on the basis of MRI (T2-weighted or FLAIR imaging). The key imaging finding was high intensity in the dentate nucleus bilaterally (82.4%). Stopping the metronidazole led to symptom remission within 8.5 days, but the MRI changes remained longer than the clinical symptoms. Two patients (6.0%) developed irreversible disturbance of consciousness. Although the mechanisms of this type of encephalopathy have not yet been elucidated, localized nerve-cell edema is likely caused by decreased metronidazole metabolism associated with liver and metabolic dysfunction. Careful observation for neurologic signs should be conducted during the treatment of brain abscesses associated with metronidazole administration, because patients with brain abscesses are naturally at high risk of metronidazole-induced encephalopathy.

  6. Resistance of Trichomonas vaginalis to metronidazole: report of the first three cases from Finland and optimization of in vitro susceptibility testing under various oxygen concentrations.

    PubMed

    Meri, T; Jokiranta, T S; Suhonen, L; Meri, S

    2000-02-01

    Trichomonas vaginalis is a globally common sexually transmitted human parasite. Many strains of T. vaginalis from around the world have been described to be resistant to the current drug of choice, metronidazole. However, only a few cases of metronidazole resistance have been reported from Europe. The resistant strains cause prolonged infections which are difficult to treat. T. vaginalis infection also increases the risk for human immunodeficiency virus transmission. We present a practical method for determining the resistance of T. vaginalis to 5-nitroimidazoles. The suggested method was developed by determining the MICs and minimal lethal concentrations (MLCs) of metronidazole and ornidazole for T. vaginalis under various aerobic and anaerobic conditions. Using this assay we have found the first three metronidazole-resistant strains from Finland, although the origin of at least one of the strains seems to be Russia. Analysis of the patient-derived and previously characterized isolates showed that metronidazole-resistant strains were also resistant to ornidazole, and MLCs for all strains tested correlated well with the MICs. The suggested MICs of metronidazole for differentiation of sensitive and resistant isolates are >75 microg/ml in an aerobic 24-h assay and >15 microg/ml in an anaerobic 48-h assay.

  7. Metronidazole (Flagyl) and Arnica Montana in the prevention of post-surgical complications, a comparative placebo controlled clinical trial.

    PubMed

    Kaziro, G S

    1984-02-01

    A double blind trial, was designed, in which 118 patients undergoing the removal of impacted wisdom teeth were randomly divided into the following groups; 41 patients received Metronidazole, 39 patients received Arnica Montana, 38 patients received the placebo. Metronidazole was more effective in pain control than Arnica (p less than 0.001) and placebo (p less than 0.01). It prevented swelling better than Arnica (p less than 0.01) and placebo (p less than 0.05) and was more effective in promoting healing than Arnica (p less than 0.01) and placebo (p greater than 0.02). Arnica Montana appeared to give rise to greater pain than placebo (p less than 0.05) and caused more swelling than the placebo (p less than 0.01).

  8. Treatment with omeprazole, metronidazole, and amoxicillin in captive South African cheetahs (Acinonyx jubatus) with spiral bacteria infection and gastritis.

    PubMed

    Lane, Emily; Lobetti, Remo; Burroughs, Richard

    2004-03-01

    Six captive cheetahs (Acinonyx jubatus) with severe gastritis diagnosed by gastric endoscopy and mucosal histopathology were treated with omeprazole, metronidazole, and amoxicillin for 3 wk. Endoscopic biopsies were performed before therapy, immediately after treatment, and 3, 7, and 19 mo after treatment. Macroscopic appearance of the stomach, histologic scoring of gastric inflammation, and the presence or absence of spiral bacteria were recorded. Spiral bacteria were absent histologically immediately after treatment but reappeared in endoscopic biopsies by 3 mo after treatment. Gastritis scores fluctuated widely during the trial but improved in five of six cheetahs by 3 mo after treatment. By 19 mo after treatment, scores were close to the pretreatment scores. Therapy with omeprazole, amoxicillin, and metronidazole was associated with temporary improvement in the degree and distribution of gastritis in some cheetahs with gastritis, suggesting that treatment may be warranted once severe gastric inflammation has been diagnosed.

  9. An active principle of Nigella sativa L., thymoquinone, showing significant antimicrobial activity against anaerobic bacteria

    PubMed Central

    Randhawa, Mohammad Akram; Alenazy, Awwad Khalaf; Alrowaili, Majed Gorayan; Basha, Jamith

    2017-01-01

    Aim/Background: Thymoquinone (TQ) is the major active principle of Nigella sativa seed (black seed) and is known to control many fungi, bacteria, and some viruses. However, the activity of TQ against anaerobic bacteria is not well demonstrated. Anaerobic bacteria can cause severe infections, including diarrhea, aspiration pneumonia, and brain abscess, particularly in immunodeficient individuals. The present study aimed to investigate the in vitro antimicrobial activity of TQ against some anaerobic pathogens in comparison to metronidazole. Methods: Standard, ATCC, strains of four anaerobic bacteria (Clostridium difficile, Clostridium perfringens, Bacteroides fragilis, and Bacteroides thetaiotaomicron), were initially isolated on special Brucella agar base (with hemin and vitamin K). Then, minimum inhibitory concentrations (MICs) of TQ and metronidazole were determined against these anaerobes when grown in Brucella agar, using serial agar dilution method according to the recommended guidelines for anaerobic organisms instructed by the Clinical and Laboratory Standards Institute. Results: TQ showed a significant antimicrobial activity against anaerobic bacteria although much weaker than metronidazole. MICs of TQ and metronidazole against various anaerobic human pathogens tested were found to be between 10-160 mg/L and 0.19-6.25 mg/L, respectively. Conclusions: TQ controlled the anaerobic human pathogenic bacteria, which supports the use of N. sativa in the treatment of diarrhea in folk medicine. Further investigations are in need for determination of the synergistic effect of TQ in combination with metronidazole and the activity of derivatives of TQ against anaerobic infections. PMID:28163966

  10. Effects of food and formulation on the relative bioavailability of bismuth biskalcitrate, metronidazole, and tetracycline given for Helicobacter pylori eradication

    PubMed Central

    Spénard, Jean; Aumais, Christian; Massicotte, Julie; Brunet, Jean-Sébastien; Tremblay, Claude; Grace, Michael; Lefebvre, Marc

    2005-01-01

    Aims To evaluate the effects of food and formulation on the pharmacokinetics of bismuth biskalcitrate, metronidazole and tetracycline when combined in a new 3-in-1 single capsule (BMT) for eradication of Helicobacter pylori. Methods In a randomized, 3 × 3 cross-over design, 23 healthy males received one dose of BMT in the fed and fasting states and equivalent doses of the three drugs given together but as separate capsules while fasting. Bioequivalence was evaluated according to 90% confidence intervals (CIs) of ratios of geometric least square means for Cmax, AUCt, and AUC∞. Results With respect to food, none of the three drugs met bioequivalence guidelines. Bismuth had lower limit CIs ranging from 12% for Cmax to 25% for AUC∞. The corresponding values for tetracycline were 59% and 51%. Metronidazole had a lower limit CI of 74% for Cmax. With respect to formulation, bismuth had lower limits of CIs ranging from 39% for Cmax to 50% for AUCt and higher limits of 146% for AUCt, metronidazole met bioequivalence guidelines, and tetracycline had lower limits of CIs between 72% for AUCt and 74% for AUC∞. Conclusions Food significantly decreased the relative bioavailability of each drug but formulation was without effect. This decrease may be beneficial when a local gastric action is needed, as confirmed by a near 90% eradication rate when this combined capsule is administered with food to treat gastro-duodenal local infection by H. pylori. PMID:16187969

  11. The effect of systemic metronidazole after non-surgical treatment in moderate and advanced periodontitis in young adults.

    PubMed

    Söder, P O; Frithiof, L; Wikner, S; Wouters, F; Engström, P E; Rubin, B; Nedlich, U; Söder, B

    1990-05-01

    The effect of adjunctive systemic metronidazole was studied in patients with moderate and advanced periodontitis recalcitrant to comprehensive non-surgical treatment. The material originated from a randomly selected part of the population aged 31 to 40 years. After non-surgical treatment of 149 patients, 98 with persisting pathological pockets greater than or equal to 5 mm (52 men and 46 women) became the subjects for the study. Clinical parameters were registered and pocket contents subjected to laboratory analysis. The subjects were randomized into two groups according to a code list known only by the manufacturer and the statistician. The test group took three 400 mg metronidazole tablets daily for 1 week and the control group took placebo tablets. Reassessment 6 months later showed statistically significant clinical improvement, with a reduction in the number of sites greater than or equal to 5 mm in both test and control groups. Complete healing, with no pockets greater than or equal to 5 mm, was noted in 30% of the test group and 9% of the control group. The difference is statistically significant and shows the supplementary effect of adjunctive metronidazole in non-surgical treatment of moderate and advanced periodontitis.

  12. Design, Optimization, and Evaluation of a Novel Metronidazole-Loaded Gastro-Retentive pH-Sensitive Hydrogel.

    PubMed

    El-Mahrouk, Galal M; Aboul-Einien, Mona H; Makhlouf, Amal I

    2016-12-01

    Floating pH-sensitive chitosan hydrogels containing metronidazole were developed for the eradication of Helicobacter pylori from the stomach. Hydrogels were prepared by crosslinking medium or high molecular weight chitosan in lyophilized solutions containing metronidazole using either citrate or tripolyphosphate (TPP) salts at 1% or 2% concentration. A 2(3) factorial design was developed to study the influence of formulation parameters on the physical characteristics of the prepared hydrogels. The interaction between hydrogel components was investigated. The morphology of the prepared hydrogels was inspected and their percentage swelling, release pattern, and moisture content were evaluated. The results revealed the absence of interaction between hydrogel components and their highly porous structure. Percentage swelling of the hydrogels was much higher, and drug release was faster in gastric pH compared with intestinal pH. The formula prepared using 2% high molecular weight chitosan and 2% TPP significantly swelled (700%) within the first 4 h and released the loaded drug over a period of 24 h. Its moisture content was not affected by storage at high relative humidity. Therefore, this formula was selected to be tested in dogs for its gastric retention (using X-ray radiography) and efficacy in the eradication of H. pylori (using histopathological and microbiological examination). The results revealed that the prepared hydrogel formula was retained in dog stomach for at least 48 h, and it was more effective against H. pylori than the commercially available oral metronidazole tablets (Flagyl®).

  13. Enhanced ultrasound-assisted degradation of methyl orange and metronidazole by rectorite-supported nanoscale zero-valent iron.

    PubMed

    Yuan, Na; Zhang, Gaoke; Guo, Sheng; Wan, Zhen

    2016-01-01

    In this study, the rectorite-supported nanoscale zero-valent iron (nZVI/R) was synthesized through a reduction method. X-ray diffraction analysis showed the existence of the nZVI in the nZVI/R composite and X-ray photoelectron spectroscopy analysis indicated that the nZVI particles were partly oxidized into iron oxide. Scanning electron microscopy analysis revealed that the nZVI particles were highly dispersed on the surface of the rectorite. The specific surface area of the nZVI/R composite is 21.43 m(2)/g, which was higher than that of rectorite (4.30 m(2)/g) and nZVI (17.97 m(2)/g). In the presence of ultrasound (US), the degradation of methyl orange and metronidazole by the nZVI/R composite was over 93% and 97% within 20 min, respectively, which is much higher than that by the rectorite and the nZVI. The degradation ratio of methyl orange and metronidazole by the nZVI/R composite under US was 1.7 and 1.8 times as high as that by the nZVI/R composite without US, respectively. The mechanism of the enhanced degradation of methyl orange and metronidazole under US irradiation was studied. These results indicate that the US/nZVI/R process has great potential application value for treatment of dye wastewater and medicine wastewater.

  14. Clinical study comparing probiotic Lactobacillus GR-1 and RC-14 with metronidazole vaginal gel to treat symptomatic bacterial vaginosis.

    PubMed

    Anukam, Kingsley C; Osazuwa, Emmanuel; Osemene, Gibson I; Ehigiagbe, Felix; Bruce, Andrew W; Reid, Gregor

    2006-10-01

    Bacterial vaginosis (BV) is particularly common in black women, and in Nigeria it is often caused by Mycoplasma, as well as Atopobium, Prevotella and Gardnerella sp. Antimicrobial metronidazole oral therapy is poorly effective in eradicating the condition and restoring the Lactobacillus microbiota in the vagina. In this study, 40 women diagnosed with BV by discharge, fishy odor, sialidase positive test and Nugent Gram stain scoring, were randomized to receive either two dried capsules containing Lactobacillus rhamnosus GR-1 and Lactobacillus reuteri RC-14 each night for 5 days, or 0.75% metronidazole gel, applied vaginally twice a day (in the morning and evening). Follow-up at day 6, 15 and 30 showed cure of BV in significantly more probiotic treated subjects (16, 17 and 18/20, respectively) compared to metronidazole treatment (9, 9 and 11/20: P=0.016 at day 6, P=0.002 at day 15 and P=0.056 at day 30). This is the first report of an effective (90%) cure of BV using probiotic lactobacilli. Given the correlation between BV and HIV, and the high risk of the latter in Nigeria, intravaginal use of lactobacilli could provide women with a self-use therapy, similar to over-the-counter anti-yeast medication, for treatment of urogenital infections.

  15. Tissue-specific metabolic activation and mutagenicity of 3-nitrobenzanthrone in MutaMouse.

    PubMed

    Chen, Guosheng; Gingerich, John; Soper, Lynda; Douglas, George R; White, Paul A

    2008-10-01

    3-Nitrobenzanthrone (3-NBA) is a mutagen and suspected human carcinogen detected in diesel exhaust, airborne particulate matter, and urban soil. We investigated the tissue specific mutagenicity of 3-NBA at the lacZ locus of transgenic MutaMouse following acute single dose or 28-day repeated-dose oral administration. In the acute high dose (50 mg/kg) exposure, increased lacZ mutant frequency was observed in bone marrow and colonic epithelium, but not in liver and bladder. In the repeated-dose study, a dose-dependent increase in lacZ mutant frequency was observed in bone marrow and liver (2- and 4-fold increase above control), but not in lung or intestinal epithelium. In addition, a concentration-dependent increase in mutant frequency (8.5-fold above control) was observed for MutaMouse FE1 lung epithelial cells exposed in vitro. 1-Nitropyrene reductase, 3-NBA reductase, and acetyltransferase activities were measured in a variety of MutaMouse specimens in an effort to link metabolic activation and mutagenicity. High 3-NBA nitroreductase activities were observed in lung, liver, colon and bladder, and detectable N-acetyltransferase activities were found in all tissues except bone marrow. The relatively high 3-NBA nitroreductase activity in MutaMouse tissues, as compared with those in Salmonella TA98 and TA100, suggests that 3-NBA is readily reduced and activated in vivo. High 3-NBA nitroreductase levels in liver and colon are consistent with the elevated lacZ mutant frequency values, and previously noted inductions of hepatic DNA adducts. Despite an absence of induced lacZ mutations, the highest 3-NBA reductase activity was detected in lung. Further studies are warranted, especially following inhalation or intratracheal exposures.

  16. Novel synthesis of carbon spheres supported nanoscale zero-valent iron for removal of metronidazole

    NASA Astrophysics Data System (ADS)

    Wang, Xiangyu; Du, Yi; Ma, Jun

    2016-12-01

    For the first time, carbon spheres-supported nanoscale zero-valent iron (NZVI/CSs) were successfully synthesized as functionalized composite via liquid phase reduction method and adopted for removal of a typical antibiotic, metronidazole (MNZ), from wastewater. The resultant composite (NZVI/CSs) exhibit higher reactivity, excellent stability, enhanced dispersion, and improved longevity over the reaction course due to the presence of the charged carboxyl groups and hydroxyl groups on the surfaces of CSs. The results show that 94.18% of MNZ was removed using NZVI/CSs after 6 min, while only 36.45% and 8.78% of MNZ were removed using NZVI and CSs, respectively. The galvanic cell system between NZVI and CSs was essential for enhancing MNZ reduction in aqueous solution. Furthermore, the new findings include kinetics for MNZ removal by NZVI/CSs composite could be well expressed by a revised two-parameter pseudo-first-order model. Finally, the possible degradation mechanism was proposed, which was based on the analysis of degraded products by high performance liquid chromatography-mass spectrometry (HPLC-MS). Different important factors impacting on MNZ removal (including mass ratio of NZVI to CSs, initial concentration, pH value and solution temperature) were investigated as well. Overall, this study provides a promising alternative material and environmental pollution management option for antibiotic wastewater treatment.

  17. Effects of radiation and vitamin C treatment on metronidazole genotoxicity in mice.

    PubMed

    Das Roy, Lopamudra; Giri, Sarbani; Singh, Supriya; Giri, Anirudha

    2013-05-15

    The impact of exposure to low dose radiation (LDR) on human health is not clear. Besides, cross adaptation or sensitization with pharmaceutical agents may modify the risk of LDR. In the present study, we analyzed the interaction of radiation and metronidazole (MTZ) in inducing chromosome aberration (CA) and micronucleus (MN) in the bone marrow cells of Balb/C mice in vivo. Further, we evaluated the efficacy of vitamin C to reduce MTZ induced genotoxicity. We found that 10, 20 and 40mg/kg of MTZ induced dose dependent increase in the frequency of CA (r=0.9923, P<0.01) as well as MN (r=0.9823, P<0.05) in polychromatic erythrocytes. However, MTZ did not affect the ratio of polychromatic erythrocytes to normochromatic erythrocytes indicating lack of cytotoxicity. Supplementation with vitamin C prior to MTZ treatment significantly reduced the frequency of CA (P<0.001) as well as MN (P<0.001). Radiation (0.5Gy) exposure prior to MTZ treatment produced a less than additive (for CA) to additive (for MN) effects. However, radiation exposure following MTZ treatment produced additive (for CA) and synergistic (for MN) effects. Further, vitamin C pre-treatment also reduced the genotoxicity indices following the combined treatment of MTZ and radiation. Our findings suggest that MTZ may sensitize bone marrow cells to radiation exposure and enhances genotoxicity. We recommend more studies on the interaction of LDR and marketed pharmaceuticals to minimize possible harmful outcomes through appropriate precautionary measures.

  18. Carbon paste electrode modified with duplex molecularly imprinted polymer hybrid film for metronidazole detection.

    PubMed

    Xiao, Ni; Deng, Jian; Cheng, Jianlin; Ju, Saiqin; Zhao, Haiqing; Xie, Jin; Qian, Duo; He, Jun

    2016-07-15

    A novel electrochemical sensor based on duplex molecularly imprinted polymer (DMIP) hybrid film modified carbon paste electrode (CPE) has been developed for highly sensitive and selective determination of metronidazole (MNZ). A conductive poly(anilinomethyltriethoxysilane) film is firstly electrodeposited on the surface of a CPE, and then a molecularly imprinted polysiloxane (MIPS) membrane is covalently covered on the film via sol-gel process. The as-constructed DMIP hybrid film, combining the advantages of MIPS and conducting MIP, can make feasible the direct and efficient signal transformation between the target analyte and the transducer, as well as enhance the imprinting recognition capability, mass transfer efficiency and the detection sensitivity. Under optimized conditions, the reduction peak currents of MNZ are linear to MNZ concentrations in the range from 4.0×10(-7) to 2.0×10(-4) molL(-1) with a detection limit of 9.1×10(-8)molL(-1). The RSD values vary from 2.9% to 4.7% for intra-day and from 3.4% to 4.2% for inter-day precision. The DMIP-based sensor has been successfully applied for the determination of MNZ in biological and pharmaceutical samples. The accuracy and reliability of the method is further confirmed by high performance liquid chromatography.

  19. Pharyngo-cutaneous fistulae after laryngectomy. Influence of previous radiotherapy and prophylactic metronidazole

    SciTech Connect

    Johansen, L.V.; Overgaard, J.; Elbrond, O.

    1988-02-15

    The development of a pharyngocutaneous fistulae is a major complication after total laryngectomy. In Denmark radiotherapy is the primary treatment for all laryngeal carcinomas. Based on the experience with conventional daily irradiation, a split-course radiation schedule was introduced in 1978. The charts of 106 consecutive patients laryngectomized for recurrence in the years 1975 to 1984 were examined. Thirty-four patients developed a fistula. An evaluation of the different radiotherapy schedules used during this period allowed a dose-response curve to be constructed. It showed a pronounced increase of fistulae with high doses of radiotherapy. Split-course radiotherapy caused a rise in late complications and did not improve tumor control. Large field sizes increased the number of fistulae. High-dose fractions showed a surprisingly high incidence of late complications. Prophylactic metronidazole (introduced in 1980) resulted in a highly significant decrease in the frequency of postoperative fistulae. Patients in whom fistula formed were hospitalized for an average of 54 days, patients without, for 22 days.

  20. Factorial analysis of the binding properties of acetylated ginger starch in metronidazole tablet formulations

    PubMed Central

    Bamiro, Oluyemisi Adebowale; Duro-Emanuel, Abioye Josephina

    2017-01-01

    Introduction: The delivery of drug is often affected by formulation processes and the excipients used in the formulation. Materials and Methods: A 23 factorial analysis was used in this study to evaluate the effect of acetylated ginger starch (AGS) (Zingiber officinale) as a binder in metronidazole tablets, in comparison to corn starch (CS) BP. The individual and interacting effects of variables (binder type X1, binder concentration X2, and compression pressure X3) used on tablet properties such as friability, crushing strength, crushing strength friability ratio (CSFR), disintegration and crushing strength friability/disintegration time ratio (CSFR/DT) were determined. The effect of these binders on the granule properties using Hausner's ratio, Carr's index (CI), angle of repose, and densities as response parameters was also determined. Results: Granules prepared with AGS had high densities and small granule sizes when compared with those containing CS. Granules containing CS have better flow properties. X1 (binder type) has a significant effect on the crushing strength of the tablet. It also had the highest effects on CSFR and CSFR/DT. The combination of XIX3 had the highest effect on crushing strength and DT. Conclusion: This study shows that, in formulations, care must be taken in choosing the excipients and the process parameters required for the formulation since these can affect the delivery of the drug individually or in combination. AGS could be useful as a binder when a tablet with low crushing strength and fast disintegration is desired.

  1. Evaluation of metronidazole nanofibers in patients with chronic periodontitis: A clinical study

    PubMed Central

    Chaturvedi, Thakur Prasad; Srivastava, Ruchi; Srivastava, Anand Kumar; Gupta, Varun; Verma, Pushpendra Kumar

    2012-01-01

    Aim: Prevention of periodontal disease progression is the primary goal of periodontal therapy. When conventional therapy is found to be inadequate in achieving periodontal health in chronic periodontitis, local antimicrobial agents are used as an adjunct to scaling and root planing (SRP), which produces encouraging results. In the present study, an attempt was made to develop a low-dose controlled-release delivery system for the treatment of periodontal infections. A new sustained release drug system of poly e-caprolactone (PCL) nanofibers containing metronidazole (MET) was successfully electrospun and evaluated clinically for periodontal diseases. The retentive nanofibres were shown to provide a controlled delivery of the drugs. Materials and Methods: Nanofibers were prepared with MET in PCL by electrospinning technique. The drug-coated nanofibers provided sustained effect up to a period of 11 days (264 h) and followed first-order release. Forty sites in seven patients (four females and three males) with chronic periodontitis (5–8 mm probing depth) were allocated in two experimental treatment groups: Group A treated with SRP + MET nanofibers and Group B treated with SRP alone (control group). All these patients were evaluated clinically for probing depth (PD), plaque index (PI), and gingival index (GI). Results: Both the treatment groups were found to be efficacious in the treatment of periodontal disease as demonstrated by improvement in PD, PI, and GI. Conclusion: Combination of SRP + MET nanofibers (Group A) resulted in added benefits, compared to the control group. PMID:23580938

  2. [Double blind randomized multicentre study of a seven-day eradication regime of Helicobacter pylori by omeprazole, clarithromycin and ornidazole vs. omeprazole, clarithromycin and metronidazole].

    PubMed

    Díte, P; Kunovská, M; Pulgretová, D; Woznica, V; Petrtýl, J; Hůlek, P; Pásková, J; Dostalík, Z; Novotný, I; Procházka, V; Hegyi, P; Zelenková, J; Samek, M; Králová, Z; Vyhnálek, P; Matejovic, F; Weinberg, J; Kyzeková, J

    2002-10-01

    Effective eradication regimes of Helicobacter pylori infections are nowadays based on administration of a substance with a strong suppressive effect on production of gastric HCl combined with two antibiotics. As suppressor of gastric HCl production unequivocally some drug from the group of proton pump blockers is used. As to antibiotics, in first line therapy the following are recommended: clarithromycin, amoxicillin, metronidazole. A problem in the eradication therapy of Helicobacter pylori infection in recent years is the increasing resistance to clarithromycin and apparently also metronidazole. In the Czech Republic the resistance to clarithromycin in relation to Helicobacter pylori is stabilized at a level lower than 3.0 %. Resistance to metronidazole was reported in 1992 within the range of 24 % - 26 %, however in 2001 it was already 36.0 %. Therefore the question arises whether it is possible under our conditions to check the increasing metronidazole resistance by a drug which by its spectrum of action resembles metronidazole while it differs from it as to its chemical structure. This is the reason why the authors implemented a trial where metronidazole was replaced by tinodazole (Avrazor, Léciva Co.). The results revealed that in the group treated with tinidazole eradication was achieved after 7-day administration of ornidazole in 93.0 %, in the group where part of the eradication regime was metronidazole eradication was 82.6 %. The tolerance of both drugs was very good. The authors recommend to include the pattern omeprazole 2 x 20 mg, clarithromycin 2 x 500 mg and tinidazole 2 x 500 mg among first line therapeutic regimes.

  3. Preliminary Studies on Two Vegetable Oil Based Self Emulsifying Drug Delivery System (SEDDS) for the Delivery of Metronidazole, A Poorly Water Soluble Drug

    NASA Astrophysics Data System (ADS)

    Obitte, N. C.; Ezeiruaku, H.; Onyishi, V. I.

    A preliminary evaluation was carried out on metronidazole-loaded Self Emulsifying Drug Delivery System (SEDDS) using two vegetable oils-Palm Kernel Oil (PKO) and Palm Oil (PO). Purification of oils, drug solubility in the oils, pre/post formulation isotropicity tests, emulsification times and release studies of metronidazole from the SEDDS were carried out. Results indicated solubility values of 4.441 and 4.654%w/w, respectively for metronidazole in PKO and PO. Preformulation isotropicity test revealed that out of the 24 batches evaluated 10 of the SEDDS formulations containing different oil: surfactant ratios and PKO:PO admixtures were found to be isotropic after 5 h. However when the SEDDS were loaded with metronidazole there was a reduction in the number (to 7) of formulations that maintained isotropicity and stability after 72 h. All the batches had emulsification times of less than two minutes except batch 4D with oil:surfactant concentration of 50:50. The release profile showed that most of the formulations released 50% of drug in less than 8 min and 85% of drug in less than 30 min. We therefore conclude that SEDDS containing the two vegetable oils are potential alternatives when immediate release and delivery of metronidazole is the primary motivation.

  4. Kinetic spectrophotometric H-point standard addition method for the simultaneous determination of diloxanide furoate and metronidazole in binary mixtures and biological fluids.

    PubMed

    Issa, Mahmoud Mohamed; Nejem, R'afat Mahmoud; Abu Shanab, Alaa Mohamed; Shaat, Nahed Talab

    2013-10-01

    Simple, reliable, and sensitive kinetic spectrophotometric method has been developed for the simultaneous determination of diloxanide furoate and metronidazole using H-point standard addition method (HPSAM). The method is based on the oxidation rate difference of diloxanide and metronidazole by potassium permanganate in basic medium. A green color has been developed and measured at 610 nm. Different experimental parameters were carefully optimized. The limiting logarithmic and the initial-rate methods were adopted for the construction of the calibration curve of each individual reaction with potassium permanganate. Under the optimum conditions, Beer's law was obeyed in the range of 1.0-20.0 and 5.0-25.0 μg ml(-1) for diloxanide furoate and metronidazole, respectively. The detection limits were 0.22 μg ml(-1) for diloxanide furoate and 0.83 μg ml(-1) for metronidazole. Correlation coefficients of the regression equations were greater than 0.9970 in all cases. The precision of the method was satisfactory; the maximum value of relative standard deviation did not exceed 1.06% (n=5). The accuracy, expressed as recovery was between 99.4% and 101.4% with relative error of 0.12 and 0.14 for diloxanide furoate and metronidazole, respectively. The proposed method was successfully applied for the simultaneous determination of both drugs in pharmaceutical dosage forms and human urine samples and compared with alternative HPLC method.

  5. Kinetic spectrophotometric H-point standard addition method for the simultaneous determination of diloxanide furoate and metronidazole in binary mixtures and biological fluids

    NASA Astrophysics Data System (ADS)

    Issa, Mahmoud Mohamed; Nejem, R.'afat Mahmoud; Shanab, Alaa Mohamed Abu; Shaat, Nahed Talab

    2013-10-01

    Simple, reliable, and sensitive kinetic spectrophotometric method has been developed for the simultaneous determination of diloxanide furoate and metronidazole using H-point standard addition method (HPSAM). The method is based on the oxidation rate difference of diloxanide and metronidazole by potassium permanganate in basic medium. A green color has been developed and measured at 610 nm. Different experimental parameters were carefully optimized. The limiting logarithmic and the initial-rate methods were adopted for the construction of the calibration curve of each individual reaction with potassium permanganate. Under the optimum conditions, Beer's law was obeyed in the range of 1.0-20.0 and 5.0-25.0 μg ml-1 for diloxanide furoate and metronidazole, respectively. The detection limits were 0.22 μg ml-1 for diloxanide furoate and 0.83 μg ml-1 for metronidazole. Correlation coefficients of the regression equations were greater than 0.9970 in all cases. The precision of the method was satisfactory; the maximum value of relative standard deviation did not exceed 1.06% (n = 5). The accuracy, expressed as recovery was between 99.4% and 101.4% with relative error of 0.12 and 0.14 for diloxanide furoate and metronidazole, respectively. The proposed method was successfully applied for the simultaneous determination of both drugs in pharmaceutical dosage forms and human urine samples and compared with alternative HPLC method.

  6. Synthesis of metronidazole-imprinted molecularly imprinted polymers by distillation precipitation polymerization and their use as a solid-phase adsorbent and chromatographic filler.

    PubMed

    Liu, Jiang; Zhang, Lu; Li Han Song, Le; Liu, Yuan; Tang, Hui; Li, Yingchun

    2015-04-01

    Metronidazole-imprinted polymers with superior recognition properties were prepared by a novel strategy called distillation-precipitation polymerization. The as-obtained polymers were characterized by Fourier-transform infrared spectroscopy, laser particle size determination and scanning electron microscopy, and their binding performances were evaluated in detail by static, kinetic and dynamic rebinding tests, and Scatchard analysis. The results showed that when the fraction of the monomers was 5 vol% in the whole reaction system, the prepared polymers afforded good morphology, monodispersity, and high adsorption capacity and excellent selectivity to the target molecule, metronidazole. The optimal binding performance is 12.41 mg/g for metronidazole just before leakage occurred and 38.51 mg/g at saturation in dynamic rebinding tests. Metronidazole-imprinted polymers were further applied as packing agents in solid-phase extraction and as chromatographic filler, both of which served for the detection of metronidazole in fish tissue. The results illustrated the recoveries of spiked samples ranged from 82.97 to 87.83% by using molecularly imprinted solid-phase extraction combined with a C18 commercial column and 93.7 to 101.2% by directly using the polymer-packed chromatographic column. The relative standard deviation of both methods was less than 6%.

  7. Spectral, thermal and kinetic studies of charge-transfer complexes formed between the highly effective antibiotic drug metronidazole and two types of acceptors: σ- and π-acceptors.

    PubMed

    Refat, Moamen S; Saad, Hosam A; Adam, Abdel Majid A

    2015-04-15

    Understanding the interaction between drugs and small inorganic or organic molecules is critical in being able to interpret the drug-receptor interactions and acting mechanism of these drugs. A combined solution and solid state study was performed to describe the complexation chemistry of drug metronidazole (MZ) which has a broad-spectrum antibacterial activity with two types of acceptors. The acceptors include, σ-acceptor (i.e., iodine) and π-acceptors (i.e., dichlorodicyanobenzoquinone (DDQ), chloranil (CHL) and picric acid (PA)). The molecular structure, spectroscopic characteristics, the binding modes as well as the thermal stability were deduced from IR, UV-vis, (1)H NMR and thermal studies. The binding ratio of complexation (MZ: acceptor) was determined to be 1:2 for the iodine acceptor and 1:1 for the DDQ, CHL or PA acceptor, according to the CHN elemental analyses and spectrophotometric titrations. It has been found that the complexation with CHL and PA acceptors increases the values of enthalpy and entropy, while the complexation with DDQ and iodine acceptors decreases the values of these parameters compared with the free MZ donor.

  8. Fabrication of metronidazole loaded poly (ε-caprolactone)/zein core/shell nanofiber membranes via coaxial electrospinning for guided tissue regeneration.

    PubMed

    He, Min; Jiang, Huiyi; Wang, Rui; Xie, Yi; Zhao, Changsheng

    2017-03-15

    To develop a biologically mimetic guided tissue regeneration (GTR) membrane with localized sustained drug release function to prevent infection, coaxial electrospinning technique was conducted to fabricate metronidazole (MNA)-loaded poly (ε-caprolactone) (PCL)/zein core/shell nanofibers. The nanofibers displayed a uniform bead-free round morphology as observed by scanning electron microscopy (SEM), and a core/shell structure as confirmed by transmission electron microscopy (TEM). X-ray diffraction (XRD) and differential scanning calorimetry (DSC) characterizations demonstrated that the MNA was well dispersed in the nanofibers matrix. Due to the encapsulation of the hydrophobic zein, the MNA was released in a controlled, sustained manner over 4days, and the released MNA showed high antibacterial activity towards anaerobic bacteria. In addition, the encapsulation of natural zein resulted in enhanced cell adhesion and proliferation, and the loading of MNA did not show any cytotoxicity. Thus, these results demonstrated that the MNA-loaded core/shell nanofibers had the potential to be used as GTR membranes with antibacterial function for extensive biomedical applications.

  9. Spectral, thermal and kinetic studies of charge-transfer complexes formed between the highly effective antibiotic drug metronidazole and two types of acceptors: σ- and π-acceptors

    NASA Astrophysics Data System (ADS)

    Refat, Moamen S.; Saad, Hosam A.; Adam, Abdel Majid A.

    2015-04-01

    Understanding the interaction between drugs and small inorganic or organic molecules is critical in being able to interpret the drug-receptor interactions and acting mechanism of these drugs. A combined solution and solid state study was performed to describe the complexation chemistry of drug metronidazole (MZ) which has a broad-spectrum antibacterial activity with two types of acceptors. The acceptors include, σ-acceptor (i.e., iodine) and π-acceptors (i.e., dichlorodicyanobenzoquinone (DDQ), chloranil (CHL) and picric acid (PA)). The molecular structure, spectroscopic characteristics, the binding modes as well as the thermal stability were deduced from IR, UV-vis, 1H NMR and thermal studies. The binding ratio of complexation (MZ: acceptor) was determined to be 1:2 for the iodine acceptor and 1:1 for the DDQ, CHL or PA acceptor, according to the CHN elemental analyses and spectrophotometric titrations. It has been found that the complexation with CHL and PA acceptors increases the values of enthalpy and entropy, while the complexation with DDQ and iodine acceptors decreases the values of these parameters compared with the free MZ donor.

  10. Tissue distribution and residue depletion of metronidazole in rainbow trout (Oncorhynchus mykiss).

    PubMed

    Mitrowska, Kamila; Pekala, Agnieszka; Posyniak, Andrzej

    2015-01-01

    Tissue distribution and residue depletion of metronidazole (MNZ) was studied in rainbow trout (Oncorhynchus mykiss) following oral administration of MNZ in feed at the average dose of 25 mg kg(-1) body weight day(-1) for 7 days at 11 ± 2°C. The MNZ concentration in feed was 0.25% while daily feed intake was 1% of body weight. The concentrations of MNZ and its main metabolite, hydroxymetronidazole (MNZOH), in fish tissues were determined by LC-MS/MS. The drug was well distributed in tissues with maximum concentrations on day 1 post-administration. At this time, the mean MNZ concentrations in muscle, skin, kidney, liver and gill were 14,999, 20,269, 15,070, 10,102 and 16,467 µg kg(-1) respectively. MNZ was converted into MNZOH with the ratio of MNZOH:MNZ up to 7% in all fish tissues throughout the withdrawal period. This shows that MNZ itself is the main residue in rainbow trout. MNZ was detected at the level close to the decision limit (0.20 µg kg(-1)) in muscle, skin and muscle with adhering skin up to 42 days, while in kidney, liver and gill it was up to 28 days post-administration. MNZOH was eliminated more rapidly from fish tissues and it was present in muscle alone up to 21 days. The elimination half-lives of MNZ and MNZOH in rainbow trout tissues were 1.83-2.53 and 1.24-2.12 days, respectively. When muscle without skin was analysed, higher MNZ and MNZOH concentrations were detected, and for a longer period of time, than in muscle with adhering skin. Thus muscle alone could be more appropriate for the effective residue control of MNZ in rainbow trout. For the same reason, it is also essential to ensure direct cooling immediately after sampling, since MNZ and its metabolite degrade in fish muscle and skin stored in non-freezing conditions.

  11. Synergistic effects of fenbendazole and metronidazole against Giardia muris in Swiss mice naturally infected.

    PubMed

    Bezagio, Renata Coltro; Colli, Cristiane Maria; Romera, Liara Izabela Lopes; Ferreira, Érika Cristina; Falavigna-Guilherme, Ana Lúcia; Gomes, Mônica Lúcia

    2017-03-01

    In this study were proposed different protocols for the treatment of mice naturally infected with Giardia muris. Male Swiss mice were divided into seven groups, with five animals each, in a blind, controlled, randomized by drawing lots and once-repeated experiment. Parasite detection and cure control were performed using the Faust method and search by trophozoites in the intestinal mucosa. Clinical parameters (weight, water and feed consumption, elimination of excreta, aspect of the fur and feces) were also evaluated. All animals were treated with metronidazole (M), fenbendazole (F), and probiotics (P), administered intragastrically, during 7 days. M1, FM1, and F1 groups were treated 1×/day; M3, FM3, and PM3 groups 3×/day; and ST (control group) received only water. After the 5th and 7th days of treatment, the animals in FM1/FM3 and PM3/M3 groups presented, respectively, negative results and remained negative in the following 10 days. Animals in F1 group consumed less water (p = 0.00010) compared with FM1/FM3/PM3. The animals in M1 group compared with FM3/M3, F1 compared with M3, and ST compared with FM1/FM3/M3/PM3 consumed a larger amount of feed (p = 0.00001). The animals in F1 group compared with FM3/M1/M3/PM3, FM1 compared with FM3, and ST compared with FM3/M1/M3/PM3 eliminated lower volume of excreta (p = 0.00001). The results show that the association between F and M potentiates the effects, indicating a synergistic action of these two drugs, and FM1 is the best protocol due to early negativity in the animals, lower concentrations of the drugs, lower risk of toxicity and stress, and less alterations in clinical parameters.

  12. Occurrence of porphyromonas gingivalis and its antibacterial susceptibility to metronidazole and tetracycline in patients with chronic periodontitis.

    PubMed

    Gamboa, Fredy; Acosta, Adriana; García, Dabeiba-Adriana; Velosa, Juliana; Araya, Natalia; Ledergerber, Roberto

    2014-01-01

    Chronic periodontitis is a multifactorial infectious disease associated with Gram-negative strict anaerobes which are immersed in the subgingival biofilm. Porphyromonas gingivalis, an important periodontal pathogen, is frequently detected in patients with chronic periodontitis. Although isolates of P. gingivalis tend to be susceptible to most antimicrobial agents, relatively little information is available on its in vitro antimicrobial susceptibility. The aim of this study was to determine the frequency of P. gingivalis in patients with chronic periodontitis and to assess antimicrobial susceptibility in terms of minimum inhibitory concentration (MIC) of clinical isolates to metronidazole and tetracycline. A descriptive, observational study was performed including 87 patients with chronic periodontitis. Samples were taken from the periodontal pocket using paper points, which were placed in thioglycollate broth. Samples were incubated for 4 hours at 37°C in anaerobic conditions and finally replated on Wilkins-Chalgren anaerobic agar (Oxoid). Bacteria were identified using the RapIDTMANAII system (Remel) and antimicrobial susceptibility was determined with the M.I.C. Evaluator test (MICE, Oxoid). P. gingivalis was identified in 30 of the 87 patients with chronic periodontitis, which represents a frequency of 34.5%. All 30 isolates (100%) were sensitive to metronidazole, with MIC values ranging from 0015-4ug/ml. Regarding tetracycline, 27 isolates (90%) were sensitive, with MIC values ranging from <0.015 to 4 ug /ml, the remaining three isolates (10%) were resistant to tetracycline with MIC values of 8ug/ ml. There was no statistically significant difference in age, gender, pocket depth, clinical attachment level and severity of periodontitis between the group of patients with chronic periodontitis and P. gingivalis and the group of patients with chronic periodontitis without P. gingivalis. In conclusion, P. gingivalis was found at a frequency of 34.5% in patients

  13. Determination and confirmation of metronidazole, dimetridazole, ronidazole and their metabolites in bovine muscle by LC-MS/MS.

    PubMed

    Granja, Rodrigo H M M; Nino, Alfredo M M; Reche, Karine V G; Giannotti, Fabio M; de Lima, Andreia C; Wanschel, Amarylis C B A; Salerno, Alessandro G

    2013-01-01

    Nitroimidazoles are a class of veterinary drugs used for the treatment and prevention of certain bacterial and protozoal diseases in poultry, swine dysentery and genital trichomoniasis in cattle. Since the safety assessment of nitroimidazoles showed them to be genotoxic, carcinogenic and mutagenic, a number of nitroimidazoles have been banned for therapeutic purposes in different countries. Moreover, nitroimidazoles have also been extensively used as growth promoters in food-producing animals. Due to their efficacious improvement in meat production and feed conversion, deliberate use still exists. Therefore, the illegal use of nitroimidazoles in animal husbandry must be monitored. A sensitive method based on LC-MS/MS for the simultaneous determination and confirmation of five banned nitroimidazole drugs including metronidazole, ronidazole, dimetridazole, metronidazole-OH (metabolite of metronidazole), and 2-hydroxymethyl-1-methyl-5-nitroimidazole (metabolite of ronidazole and dimetridazole) in bovine muscle, using ronidazole-d3 as an internal standard, was developed and validated. After extraction with ethyl acetate and evaporation, the nitroimidazoles were reconstituted in petroleum ether and purified, and LC-MS/MS analysis was performed. The method was validated according to Brazilian Regulation 24/2009 (equivalent to European Union Decision 2002/657/EC). Parameters such as decision limit (CCα), detection capability (CCβ), precision, accuracy, uncertaincy and ruggedness were determined. Average accuracy of the five nitroimidazoles from bovine muscle fortified at 5 levels (0.5, 1.0, 1.5, 2.0 and 2.5 μg kg(-1)) ranged from 96% to 103%. The calculated CCα ranged from 0.0 to 0.17 μg kg(-1); CCβ ranged from 0.08 to 0.41 μg kg(-1). A complete statistical analysis was performed and the results indicate that the method is robust when subjected to day-to-day analytical variations.

  14. Zero order and signal processing spectrophotometric techniques applied for resolving interference of metronidazole with ciprofloxacin in their pharmaceutical dosage form

    NASA Astrophysics Data System (ADS)

    Attia, Khalid A. M.; Nassar, Mohammed W. I.; El-Zeiny, Mohamed B.; Serag, Ahmed

    2016-02-01

    Four rapid, simple, accurate and precise spectrophotometric methods were used for the determination of ciprofloxacin in the presence of metronidazole as interference. The methods under study are area under the curve, simultaneous equation in addition to smart signal processing techniques of manipulating ratio spectra namely Savitsky-Golay filters and continuous wavelet transform. All the methods were validated according to the ICH guidelines where accuracy, precision and repeatability were found to be within the acceptable limits. The selectivity of the proposed methods was tested using laboratory prepared mixtures and assessed by applying the standard addition technique. So, they can therefore be used for the routine analysis of ciprofloxacin in quality-control laboratories.

  15. Scuticociliatid ciliate outbreak in Australian potbellied seahorse, Hippocampus abdominalis (Lesson, 1827): clinical signs, histopathologic findings, and treatment with metronidazole.

    PubMed

    Di Cicco, Emiliano; Paradis, Erika; Stephen, Craig; Turba, Maria Elena; Rossi, Giacomo

    2013-06-01

    A severe outbreak of scuticociliatosis occurred in Australian pot-bellied seahorse, Hippocampus abdominalis (Lesson, 1872), kept at the Vancouver Aquarium Marine Science Centre (Vancouver, British Columbia, Canada). Clinical signs included anorexia, lethargy, irregular respiration, and death. Cytology and histopathology revealed a high number of histophagous ciliated protozoa within the tissues. The parasite, identified as Philasterides dicentrarchi, was observed in several internal organs that appeared edematous and hemorrhagic upon postmortem examination. Severe histopathologic lesions were reported in particular in the ovary, the kidney, and the intestine. This infection was successfully treated with metronidazole via bath therapy. No further evidence of this parasite was found in the treated fish.

  16. Effect of olive leaf, Satureja khuzestanica, and Allium sativum extracts on Giardia lamblia cysts compared with metronidazole in vitro.

    PubMed

    Fallahi, Sh; Rostami, A; Delfan, B; Pournia, Y; Rashidipour, M

    2016-12-01

    Giardia lamblia is one of the common causes of worldwide diarrhea in children. Appropriate medicinal treatment for giardiasis is available but there are some evidences of drug resistance, insufficient efficacy, and unpleasant side effects. In order to reach a more natural drug with suitable efficacy and the lowest side effects, the effects of the hydroalcoholic extracts of olive leaf, Satureja khuzestanica, and Allium sativum on G. lamblia cysts were evaluated in vitro, as well as antigiardial effect of the extracts was compared with metronidazole as the drug of choice. 2 and 5 mg of the plants extracts and powder of metronidazole 250 mg pills were added to 1 ml of G. lamblia cysts suspension (containing 5,000 cyst/ml normal saline), and the percentages of bioavailability of G. lamblia cysts were examined at the 2nd and 4th h after exposure and in 4 and 37 °C temperatures using eosin 0.1 % and a haemocytometer. The data were analyzed by multiway ANOVA test, Tukey's test, and the SPSS software, version 18. The examinations demonstrated that olive leaf extract had the most fatality rate on G. lamblia cysts in vitro (37.90 ± 7.01 %), followed by the extract of S. khuzestanica (32.52 ± 9.07 %). Metronidazole 250 mg pills had relatively effective fatality rate on G. lamblia cysts in vitro (28.75 ± 10.30 %), whereas A. sativum (garlic) had the lowest fatality effect on G. lamblia cysts in vitro (22.65 ± 10.47 %). With respect to higher fatality effect of olive leaf and S. khuzestanica extracts compared with metronidazole in vitro, these plants can be used as suitable candidates to make new antigiardial drugs with low side effects and without drug resistance in the treatment of giardiasis in children.

  17. Population pharmacokinetic models for cefuroxime and metronidazole used in combination as prophylactic agents in colorectal surgery: Model-based evaluation of standard dosing regimens.

    PubMed

    Asín-Prieto, Eduardo; Soraluce, Amaia; Trocóniz, Iñaki F; Campo Cimarras, Eugenia; Sáenz de Ugarte Sobrón, Jaione; Rodríguez-Gascón, Alicia; Isla, Arantxazu

    2015-05-01

    The antibiotics used for prophylaxis in colorectal surgery must maintain appropriate plasma concentrations during the entire surgery to avoid surgical site infections caused by aerobes and anaerobes; cefuroxime plus metronidazole is one of the combinations used. The aim of this study was to evaluate the adequacy of cefuroxime plus metronidazole administration as prophylaxis in colorectal surgery. In total, 63 patients electively undergoing rectal or colon surgery were administered 1500mg of cefuroxime and 1500mg of metronidazole in 15-min and 1-h infusions, respectively, prior to surgery. Blood samples were withdrawn during and after surgery for determination of plasma concentrations by high-performance liquid chromatography. Population pharmacokinetic models were developed using NONMEM 7.2.0. Pharmacokinetic/pharmacodynamic (PK/PD) simulations were performed to explore the ability of different dosage regimens to achieve the pharmacodynamic targets. Pharmacokinetics for both antibiotics were best described by a two-compartment model. Elimination of cefuroxime was conditioned by creatinine clearance (CLCr). The half-life of cefuroxime was 1.5h for patients with normal renal function and 4.9h in patients with renal impairment. Elimination and distribution of metronidazole were affected by patient body weight (BW). PK/PD analysis revealed that a single-dose protocol of 1500mg of cefuroxime and metronidazole is adequate in short surgeries (≤2h). However, for longer surgeries, recommendations are suggested depending on the patient's CLCr and BW. Additional doses of cefuroxime are needed for patients with moderate renal impairment or those presenting normal renal function. For metronidazole, an additional dose is needed for patients with a BW of 90kg.

  18. A penicillin- and metronidazole-resistant Clostridium botulinum strain responsible for an infant botulism case.

    PubMed

    Mazuet, C; Yoon, E-J; Boyer, S; Pignier, S; Blanc, T; Doehring, I; Meziane-Cherif, D; Dumant-Forest, C; Sautereau, J; Legeay, C; Bouvet, P; Bouchier, C; Quijano-Roy, S; Pestel-Caron, M; Courvalin, P; Popoff, M R

    2016-07-01

    The clinical course of a case of infant botulism was characterized by several relapses despite therapy with amoxicillin and metronidazole. Botulism was confirmed by identification of botulinum toxin and Clostridium botulinum in stools. A C. botulinum A2 strain resistant to penicillins and with heterogeneous resistance to metronidazole was isolated from stool samples up to 110 days after onset. Antibiotic susceptibility was tested by disc agar diffusion and MICs were determined by Etest. Whole genome sequencing allowed detection of a gene cluster composed of blaCBP for a novel penicillinase, blaI for a regulator, and blaR1 for a membrane-bound penicillin receptor in the chromosome of the C. botulinum isolate. The purified recombinant penicillinase was assayed. Resistance to β-lactams was in agreement with the kinetic parameters of the enzyme. In addition, the β-lactamase gene cluster was found in three C. botulinum genomes in databanks and in two of 62 genomes of our collection, all the strains belonging to group I C. botulinum. This is the first report of a C. botulinum isolate resistant to penicillins. This stresses the importance of antibiotic susceptibility testing for adequate therapy of botulism.

  19. Simultaneous determination of metronidazole and spiramycin in bulk powder and in tablets using different spectrophotometric techniques.

    PubMed

    Khattab, Fatma I; Ramadan, Nesrin K; Hegazy, Maha A; Ghoniem, Nermine S

    2010-01-01

    Metronidazole (MZ) is an anti-infective drug used in the treatment of anaerobic bacterial and protozoa infections in humans. It is also used as a veterinary antiparasitic drug. Spiramycin (SP) is a medium-spectrum antibiotic with high effectiveness against Gram-positive bacteria. Three simple, sensitive, selective and precise spectrophotometric methods were developed and validated for the simultaneous determination of MZ and SP in their pure form and in pharmaceutical formulations. In methods A and B, MZ was determined by the application of direct spectrophotometry and by measuring its zero-order (D(0)) absorption spectra at its λ(max) = 311 nm. In method A, SP was determined by the application of first derivative spectrophotometry (D(1)) and by measuring the amplitude at 218.3 nm. In method B, the first derivative of the ratio spectra (DD(1)) was applied, and SP was determined by measuring the peak amplitude at 245.6 nm. Method C entailed mean centering of the ratio spectra (MCR), which allows the determination of both MZ and SP. The methods developed were used for the determination of MZ and SP over a concentration range of 5-25 µg ml(-1). The proposed methods were used to determine both drugs in their pure, powdered forms with mean percentage recoveries of 100.16 ± 0.73 for MZ in methods A and B, 101.10 ± 0.90 in method C, 100.09 ± 0.70, 100.02 ± 0.88 and 100.49 ± 1.26 for SP in methods A, B and C, respectively. The proposed methods were proved using laboratory-prepared mixtures of the two drugs and were successfully applied to the analysis of MZ and SP in tablet formulation without any interference from each other or from the excipients. The results obtained by applying the proposed methods were compared statistically with a reported HPLC method and no significant difference was observed between these methods regarding both accuracy and precision.

  20. Determination of metronidazole residues in water, sediment and fish tissue samples.

    PubMed

    Wagil, Marta; Maszkowska, Joanna; Białk-Bielińska, Anna; Caban, Magda; Stepnowski, Piotr; Kumirska, Jolanta

    2015-01-01

    Metronidazole (MNZ) is an antibacterial and antiprotozoal drug used in veterinary and human medicine. Its continual entry into the environment and its biological properties may have significant, long-term effects on the stability of ecosystems because MNZ and its metabolites possess mutagenic, carcinogenic and toxic properties. For this reason, the application of MNZ in food-producing species is prohibited in the EU, the USA and other countries. To ensure human food safety and to protect the environment, robust and reliable screening and confirmatory tests capable of the low-level detection of MNZ residues are required. The development of methods for MNZ determination in biological and environmental samples is thus an important analytical task in environmental and food science. This work focuses on the evaluation of a method for determining MNZ in water, sediment and fish tissue samples using liquid chromatography--ion trap mass spectrometry (LC-MS/MS). MNZ was extracted from waters on Strata XC cartridges using solid phase extraction (SPE), and from sediments and fish tissues by solid-liquid extraction (sediment: 15 mL 0.1 M HCl (pH=0.6), 15 min; fish tissue: 15 mL 1% CH3COOH in ACN, 1 min; drying: 5 g MgSO4(anhyd.; 30 s) with SPE purification of the extracts (from sediment: Strata XC cartridge; from fish tissue: Supelco NH2 cartridge). The optimal procedure that we developed was validated in order to confirm its reliability and sensitivity. Matrix effects (ME) were established. Absolute recoveries ranged from 89.3% to 97.2%, and the method detection limits were 3.4 ng L(-1) (water samples), 0.4 ng g(-1) (sediment samples) and 0.3 ng g(-1) (tissue samples). These methods were used to determine MNZ in surface waters, sediments and fish tissues from the Polish River Gościcina; MNZ was found in all these matrices. The highest concentrations in water, sediment and tissue were 136.2 ng L(-1), 12.0 ng g(-1) and 1.5 ng g(-1) respectively. The results confirmed that

  1. Repercussions of intraalveolar placement of combination of 0.2% chlorhexidine & 10 Mg metronidazole gel on the occurrence of dry sockets- A randomized control trial

    PubMed Central

    Raval, Rushik; Bansal, Anupam; Kumawat, Vinod

    2017-01-01

    Background To evaluate the effects of intraalveolar placement of gel containing 0.2% chlorhexidine and 10gm of metronidazole on the incidence of alveolar osteitis. Material and Methods A total of 300 impacted third molars were extracted in 150 patients enrolled in this trial. In each subject a socket was randomly selected and packed to the crest of alveolar ridge with the gel. The contralateral socket was packed with placebo dressing. The occurrence of dry socket was assessed during 3rd and 5th postoperative days .The data was analysed using a meta analytical program. Study Design Double blind, prospective, placebo controlled trial. Results The combination of metronidazole + chlorhexidine gel significantly reduced dry socket incidence from 22.6% to 6.6% (P ≤ 0.001) [McNemar and chi-square tests]. Conclusions The decrease in incidence of adverse reactions and complications related to local application of metronidazole and chlorhexidine gel explains its clinical use, specifically in mandibular molar extractions where the chances of dry sockets are high. Key words:Chlorhexidine, dry socket, intra-alveolar, metronidazole, placebo. PMID:28210450

  2. Proton pump inhibitor-amoxicillin-clarithromycin versus proton pump inhibitor-amoxicillin-metronidazole as first-line Helicobacter pylori eradication therapy.

    PubMed

    Nishizawa, Toshihiro; Suzuki, Hidekazu; Suzuki, Masayuki; Takahashi, Masahiko; Hibi, Toshifumi

    2012-09-01

    The aim of this study was to compare the efficacy and tolerability of the first-line Helicobacter pylori (H. pylori) eradication regimen composed of proton pump inhibitor, clarithromycin, and amoxicillin, with those of a regimen composed of proton pump inhibitor, metronidazole, and amoxicillin. Data of patients, who were administered the first-line H. pylori eradication regimen at Tokyo Medical Center between 2008 and 2011, were reviewed. All patients had H. pylori gastritis without peptic ulcer disease. The 7-day triple regimen composed of lansoprazole, clarithromycin, and amoxicillin was administered to 55 patients, and that composed of omeprazole, metronidazole, and amoxicillin was administered to 55 patients. Intention-to-treat and per-protocol eradication rates were 74.5 and 80.4%, respectively, for the regimen of lansoprazole, clarithromycin, and amoxicillin, whereas the corresponding rates were 96.4 and 100%, respectively, for the regimen of omeprazole, metronidazole, and amoxicillin. In conclusion, first-line H. pylori eradication therapy composed of omeprazole, metronidazole, and amoxicillin was significantly more effective than that composed of lansoprazole, clarithromycin, and amoxicillin, without differences in tolerability.

  3. The Design of Nanostructured Metronidazole-Loaded HPC/Oxide Xerogel Composites: Influence of the Formulation Parameters on In Vitro Characterisation.

    PubMed

    Czarnobaj, Katarzyna

    2015-10-01

    In this study, oxide and polymer/oxide xerogels with metronidazole were prepared and examined as carriers of drug for the local application to the bone. The nanoporous SiO2-CaO-P2O5 and HPC-SiO2-CaO-P2O5 xerogel materials with different amounts of the polymer [hydroxypropyl cellulose (HPC)] were prepared using the sol-gel technology, and their physicochemical properties were characterised with respect to chemical structure [by Fourier transform infrared spectroscopy (FTIR)], porosity and the specific surface area of solids (BET), crystallinity [by X-ray powder diffraction (XRD)], morphology [by scanning electron microscope (SEM)] and the in vitro release of the metronidazole over time (by UV-vis spectroscopy, in the ultraviolet light region). HPC-modified oxide xerogels as the carriers of drug showed slower release of metronidazole, due to the structure and stronger interactions with drug as compared with the pure oxide xerogel. Kinetic analysis indicated diffusional mechanism of drug release from all xerogel carriers. HPC addition to the oxide material resulted in a decrease in the porosity and improved the bioactive properties of xerogels. Obtained results for xerogel composites suggest that the metronidazole-loaded xerogels could be attractive candidates for local delivery systems particularly to a bone.

  4. THE EFFICACY OF THREE MEDICINAL PLANTS; GARLIC, GINGER AND MIRAZID AND A CHEMICAL DRUG METRONIDAZOLE AGAINST CRYPTOSPORIDIUM PARVUM: II-HISTOLOGICAL CHANGES.

    PubMed

    Abouel-Nour, Mohamed F; El-Shewehy, Dina Magdy M; Hamada, Shadia F; Morsy, Tosson A

    2016-04-01

    Cryptosporidiosis parvum is a zoonotic protozoan parasite infects intestinal epithelial cells of man and animals causing a major health problem. This study was oriented to evaluate the protective and curative capacity of garlic, ginger and mirazid in comparison with metronidazole drug (commercially known) against Cryptosporidium in experimental mice. Male Swiss Albino mice experimentally infected with C. parvum were treated with medicinal plants extracts (Ginger, Mirazid, and Garlic) as compared to chemical drug Metronidazole. Importantly, C. parvum-infected mice treated with ginger, Mirazid, garlic and metronidazole showed a complete elimination in shedding oocysts by 9th day PI. The reduction and elimination of shedding oocysts in response to the treatments might be attributable to a direct effect on parasite growth in intestines, sexual phases production and/or the formation of oocysts. The results were evaluated histopathological examination of ideum section of control mice (uninfected, untreated) displayed normal architecture of the villi. Examiination of infected mice ileum section (infected, untreated) displayed histopathological alterations from uninfected groups. Examination of ileum section prepared from mice treated with garlic, ginger, mirazid, and metronidazole displayed histopathological alterations from that of the control groups, and showed marked histologic correction in the pattern with the four regimes used in comparison to control mice. Garlic successfully eradicated oocysts of infected mice from stool and intestine. Supplementation of ginger to infected mice markedly corrected elevation in the inflammatory risk factors and implied its potential antioxidant, anti-inflammatory and immunomodulatory capabilities. Infected mice treated with ginger, mirazid, garlic and metronidazole showed significant symptomatic improvements during treatment.

  5. Enhancement of the Antifungal Activity of Antimicrobial Drugs by Eugenia uniflora L.

    PubMed Central

    Santos, Karla K.A.; Matias, Edinardo F.F.; Tintino, Saulo R.; Souza, Celestina E.S.; Braga, Maria F.B.M.; Guedes, Gláucia M.M.; Costa, José G.M.; Menezes, Irwin R.A.

    2013-01-01

    Abstract Candidiasis is the most frequent infection by opportunistic fungi such as Candida albicans, Candida tropicalis, and Candida krusei. Ethanol extract from Eugenia uniflora was assayed, for its antifungal activity, either alone or combined with four selected chemotherapeutic antimicrobial agents, including anphotericin B, mebendazole, nistatin, and metronidazole against these strains. The obtained results indicated that the association of the extract of E. uniflora to metronidazole showed a potential antifungal activity against C. tropicalis. However, no synergistic activity against the other strains was observed, as observed when the extract was associated with the other, not enhancing their antifungal activity. PMID:23819641

  6. Metronidazole and interstitial implantation in the treatment of extensive recurrent head and neck cancers. [/sup 192/Ir

    SciTech Connect

    Orr, L.E.; Puthawala, A.; Nisar Syed, A.M.; Fleming, P.A.

    1981-07-01

    Twenty-three patients with recurrent or persistent epidermoid carcinoma of the oral cavity, all of whom had failed primary antitumor therapy, were treated with interstitial irradiation and a radio-sensitizer. All patients underwent afterloading interstitial iridium-192 implants. Each subject received 6 g/m/sup 2/ metronidazole administered orally in one dose every 48 hours for the duration of the implant. The radiation dose ranged between 4500 and 6500 rads in 65 to 120 hours. Sixteen of 23 patients (69.6%) demonstrated complete regression of local disease, usually within 12 weeks. Ten of the 23 individuals (43%) remain alive and disease-free with an average follow-up of 25 months since the completion of the regimen. Neurologic and hepatic toxicity were notably absent. Nausea, mild diarrhea and accentuation of the radiation-induced mucositis constituted the principal side effects.

  7. Application of derivative spectrophotometry under orthogonal polynomial at unequal intervals: Determination of metronidazole and nystatin in their pharmaceutical mixture

    NASA Astrophysics Data System (ADS)

    Korany, Mohamed A.; Abdine, Heba H.; Ragab, Marwa A. A.; Aboras, Sara I.

    2015-05-01

    This paper discusses a general method for the use of orthogonal polynomials for unequal intervals (OPUI) to eliminate interferences in two-component spectrophotometric analysis. In this paper, a new approach was developed by using first derivative D1 curve instead of absorbance curve to be convoluted using OPUI method for the determination of metronidazole (MTR) and nystatin (NYS) in their mixture. After applying derivative treatment of the absorption data many maxima and minima points appeared giving characteristic shape for each drug allowing the selection of different number of points for the OPUI method for each drug. This allows the specific and selective determination of each drug in presence of the other and in presence of any matrix interference. The method is particularly useful when the two absorption spectra have considerable overlap. The results obtained are encouraging and suggest that the method can be widely applied to similar problems.

  8. Changes in vaginal bacterial concentrations with intravaginal metronidazole therapy for bacterial vaginosis as assessed by quantitative PCR.

    PubMed

    Fredricks, David N; Fiedler, Tina L; Thomas, Katherine K; Mitchell, Caroline M; Marrazzo, Jeanne M

    2009-03-01

    Several fastidious bacteria have been associated with bacterial vaginosis (BV) using broad-range bacterial PCR methods such as consensus sequence 16S rRNA gene PCR, but their role in BV remains poorly defined. We describe changes in vaginal bacterial concentrations following metronidazole therapy for BV. Vaginal swabs were collected from women with BV diagnosed using Amsel clinical criteria, and vaginal fluid was assessed by Gram stain to generate Nugent scores. Follow-up swabs were collected 1 month after a 5-day course of vaginal 0.75% metronidazole gel and analyzed for 24 subjects with cured BV and 24 subjects with persistent BV. Changes in bacterial concentrations were measured using eight bacterium-specific 16S rRNA gene quantitative PCR assays. DNA from several fastidious BV-associated bacteria (BVAB) were present at high concentrations in the vagina prior to treatment. Successful antibiotic therapy resulted in 3- to 4-log reductions in median bacterial loads of BVAB1 (P=0.02), BVAB2 (P=0.0004), BVAB3 (P=0.03), a Megasphaera-like bacterium (P<0.0001), Atopobium species (P<0.0001), Leptotrichia/Sneathia species (P=0.0002), and Gardnerella vaginalis (P<0.0001). Median posttreatment bacterial levels did not change significantly in subjects with persistent BV except for a decline in levels of BVAB3. The presence or absence of BV is reflected by vaginal concentrations of BV-associated bacteria such as BVAB1, BVAB2, Leptotrichia/Sneathia species, Atopobium species, Gardnerella vaginalis, and a Megasphaera-like bacterium, suggesting that these bacteria play an important role in BV pathogenesis and may be suitable markers of disease and treatment response.

  9. Changes in Vaginal Bacterial Concentrations with Intravaginal Metronidazole Therapy for Bacterial Vaginosis as Assessed by Quantitative PCR▿

    PubMed Central

    Fredricks, David N.; Fiedler, Tina L.; Thomas, Katherine K.; Mitchell, Caroline M.; Marrazzo, Jeanne M.

    2009-01-01

    Several fastidious bacteria have been associated with bacterial vaginosis (BV) using broad-range bacterial PCR methods such as consensus sequence 16S rRNA gene PCR, but their role in BV remains poorly defined. We describe changes in vaginal bacterial concentrations following metronidazole therapy for BV. Vaginal swabs were collected from women with BV diagnosed using Amsel clinical criteria, and vaginal fluid was assessed by Gram stain to generate Nugent scores. Follow-up swabs were collected 1 month after a 5-day course of vaginal 0.75% metronidazole gel and analyzed for 24 subjects with cured BV and 24 subjects with persistent BV. Changes in bacterial concentrations were measured using eight bacterium-specific 16S rRNA gene quantitative PCR assays. DNA from several fastidious BV-associated bacteria (BVAB) were present at high concentrations in the vagina prior to treatment. Successful antibiotic therapy resulted in 3- to 4-log reductions in median bacterial loads of BVAB1 (P = 0.02), BVAB2 (P = 0.0004), BVAB3 (P = 0.03), a Megasphaera-like bacterium (P < 0.0001), Atopobium species (P < 0.0001), Leptotrichia/Sneathia species (P = 0.0002), and Gardnerella vaginalis (P < 0.0001). Median posttreatment bacterial levels did not change significantly in subjects with persistent BV except for a decline in levels of BVAB3. The presence or absence of BV is reflected by vaginal concentrations of BV-associated bacteria such as BVAB1, BVAB2, Leptotrichia/Sneathia species, Atopobium species, Gardnerella vaginalis, and a Megasphaera-like bacterium, suggesting that these bacteria play an important role in BV pathogenesis and may be suitable markers of disease and treatment response. PMID:19144794

  10. Collateral Effects of Antibiotics: Carbadox and Metronidazole Induce VSH-1 and Facilitate Gene Transfer among Brachyspira hyodysenteriae Strains▿

    PubMed Central

    Stanton, Thaddeus B.; Humphrey, Samuel B.; Sharma, Vijay K.; Zuerner, Richard L.

    2008-01-01

    Brachyspira hyodysenteriae is an anaerobic spirochete and the etiologic agent of swine dysentery. The genome of this spirochete contains a mitomycin C-inducible, prophage-like gene transfer agent designated VSH-1. VSH-1 particles package random 7.5-kb fragments of the B. hyodysenteriae genome and transfer genes between B. hyodysenteriae cells. The chemicals and conditions inducing VSH-1 production are largely unknown. Antibiotics used in swine management and stressors inducing traditional prophages might induce VSH-1 and thereby stimulate lateral gene transfer between B. hyodysenteriae cells. In these studies, VSH-1 induction was initially detected by a quantitative real-time reverse transcriptase PCR assay evaluating increased transcription of hvp38 (VSH-1 head protein gene). VSH-1 induction was confirmed by detecting VSH-1-associated 7.5-kb DNA and VSH-1 particles in B. hyodysenteriae cultures. Nine antibiotics (chlortetracycline, lincomycin, tylosin, tiamulin, virginiamycin, ampicillin, ceftriaxone, vancomycin, and florfenicol) at concentrations affecting B. hyodysenteriae growth did not induce VSH-1 production. By contrast, VSH-1 was detected in B. hyodysenteriae cultures treated with mitomycin C (10 μg/ml), carbadox (0.5 μg/ml), metronidazole (0.5 μg/ml), and H2O2 (300 μM). Carbadox- and metronidazole-induced VSH-1 particles transmitted tylosin and chloramphenicol resistance determinants between B. hyodysenteriae strains. The results of these studies suggest that certain antibiotics may induce the production of prophage or prophage-like elements by intestinal bacteria and thereby impact intestinal microbial ecology. PMID:18359835

  11. Antianaerobic activity of sulopenem compared to six other agents.

    PubMed

    Ednie, Lois M; Appelbaum, Peter C

    2009-05-01

    Agar dilution MIC methodology was used to compare the activity of sulopenem with those of amoxicillin/clavulanate, ampicillin/sulbactam, piperacillin-tazobactam, imipenem, clindamycin, and metronidazole against 431 anaerobes. Overall, MIC(50)/(90) values were as follows: sulopenem, 0.25/1.0 microg/ml; amoxicillin/clavulanate, 0.5/2.0 microg/ml; ampicillin/sulbactam, 0.5/4.0 microg/ml; piperacillin/tazobactam, 0.25/8.0 microg/ml; imipenem, 0.06/1.0 microg/ml; clindamycin, 0.25/16.0 microg/ml; and metronidazole, 1.0/4.0 microg/ml.

  12. Enhanced amperometric detection of metronidazole in drug formulations and urine samples based on chitosan protected tetrasulfonated copper phthalocyanine thin-film modified glassy carbon electrode.

    PubMed

    Meenakshi, S; Pandian, K; Jayakumari, L S; Inbasekaran, S

    2016-02-01

    An enhanced electrocatalytic reduction of metronidazole antibiotic drug molecule using chitosan protected tetrasulfonated copper phthalocyanine (Chit/CuTsPc) thin-film modified glassy carbon electrode (GCE) has been developed. An irreversible reduction occurs at -0.47V (vs. Ag/AgCl) using Chit/CuTsPc modified GCE. A maximum peak current value is obtained at pH1 and the electrochemical reduction reaction is a diffusion controlled one. The detection limit is found to be 0.41nM from differential pulse voltammetry (DPV) method. This present investigation method is adopted for electrochemical detection of metronidazole in drug formulation and urine samples by using DPV method.

  13. Mechanism of binding of the radiosensitizers metronidazole and misonidazole (RO-07-0582) to bovine and human serum albumin: a proton NMR study

    SciTech Connect

    Sulkowska, A.; Lubas, B.; Wilczok, T.

    1981-01-01

    High-resolution proton NMR spectra of the radiosensitizer metronidazole and its derivative misonidazole (RO-07-0582) were measured in D/sub 2/O at resonance frequency 60 MHz and interpreted in the aliphatic and aromatic regions. The linewidths of the NMR peaks attributed to individual fragments of nitroimidazole molecules were then analyzed in the presence of bovine and human serum albumin. With increasing concentration of serum albumin, a selectively larger broadening of the lines attributable to the protons of the aliphatic moieties than of those of the imidazole rings was observed for both compounds. This broadening for misonidazole strongly depends on the ionic strength of the solution. The results indicate a specific immobilization of the molecules of both radiosensitizers during their interaction with serum albumin and the involvement of the aliphatic chains of misonidazole and metronidazole as the primary binding sites.

  14. Idiopathic Facial Aseptic Granuloma in a 13-Year-Old Boy Dramatically Improved with Oral Doxycycline and Topical Metronidazole: Evidence for a Link with Childhood Rosacea

    PubMed Central

    Orion, Camille; Sfecci, Alicia; Tisseau, Laurent; Darrieux, Laure; Safa, Gilles

    2016-01-01

    Idiopathic facial aseptic granuloma (IFAG) is a rare, benign pediatric dermatological lesion that occurs in children between 8 months and 13 years of age. The pathogenesis of IFAG is still unclear but it is likely to be associated with granulomatous rosacea in childhood. Here we describe a case of IFAG in a 13-year-old boy who showed a dramatic response to oral doxycycline and topical metronidazole, which supports the hypothesis that IFAG may belong to the spectrum of rosacea. PMID:27920676

  15. Effect of MMX® mesalamine coadministration on the pharmacokinetics of amoxicillin, ciprofloxacin XR, metronidazole, and sulfamethoxazole: results from four randomized clinical trials

    PubMed Central

    Pierce, David; Corcoran, Mary; Martin, Patrick; Barrett, Karen; Inglis, Susi; Preston, Peter; Thompson, Thomas N; Willsie, Sandra K

    2014-01-01

    Background MMX® mesalamine is a once daily oral 5-aminosalicylic acid formulation, effective in induction and maintenance of ulcerative colitis remission. Patients on long-term mesalamine maintenance may occasionally require concomitant antibiotic treatment for unrelated infections. Aim To evaluate the potential for pharmacokinetic interactions between MMX mesalamine and amoxicillin, ciprofloxacin extended release (XR), metronidazole, or sulfamethoxazole in four open-label, randomized, placebo-controlled, two-period crossover studies. Methods In all four studies, healthy adults received placebo once daily or MMX mesalamine 4.8 g once daily on days 1–4 in one of two treatment sequences. In studies 1 and 2, subjects also received a single dose of amoxicillin 500 mg (N=62) or ciprofloxacin XR 500 mg (N=30) on day 4. In studies 3 and 4, subjects received metronidazole 750 mg twice daily on days 1–3 and once on day 4 (N=30); or sulfamethoxazole 800 mg/trimethoprim 160 mg twice daily on days 1–3 and once on day 4 (N=44). Results MMX mesalamine had no significant effects on systemic exposure to amoxicillin, ciprofloxacin, or metronidazole; the 90% confidence intervals (CIs) around the geometric mean ratios (antibiotic + MMX mesalamine: antibiotic + placebo) for maximum plasma concentration (Cmax) and area under the plasma concentration–time curve (AUC) fell within the predefined equivalence range (0.80–1.25). Sulfamethoxazole exposure increased by a statistically significant amount when coadministered with MMX mesalamine; however, increased exposure (by 12% in Cmax at steady state; by 15% in AUC at steady state) was not considered clinically significant, as the 90% CIs for each point estimate fell entirely within the predefined equivalence range. Adverse events in all studies were generally mild. Conclusion MMX mesalamine may be coadministered with amoxicillin, ciprofloxacin, metronidazole, or sulfamethoxazole, without affecting pharmacokinetics or safety of

  16. Addition of Ceftriaxone and Amikacin to a Ciprofloxacin plus Metronidazole Regimen for Preventing Infectious Complications of Transrectal Ultrasound-Guided Prostate Biopsy: A Randomized Controlled Trial

    PubMed Central

    Izadpanahi, Mohammad-Hossein; Majidi, Seyed Mahmood; Khorrami, Mohammad-Hatef; Mohammadi-Sichani, Mehrdad

    2017-01-01

    Background. The objective of this study was to evaluate the efficacy of adding single doses of ceftriaxone and amikacin to a ciprofloxacin plus metronidazole regimen on the reduction of infectious complications following transrectal ultrasound-guided prostate biopsy (TRUS Bx). Materials and Methods. Four hundred and fifty patients who were candidates for TRUS Bx were divided into two groups of 225 each. The control group received ciprofloxacin 500 mg orally every 12 hours together with metronidazole 500 mg orally every 8 hours from the day prior to the procedure until the fifth postoperative day. In the second group, single doses of ceftriaxone 1 g by intravenous infusion and amikacin 5 mg/kg intramuscularly were administered 30–60 minutes before TRUS Bx in addition to the oral antimicrobials described for group 1. The incidence of infection was compared between the groups. Results. The incidence of infectious complications in the intervention group was significantly lower than that in the control group (4.6% versus 0.9%, p = 0.017). Conclusion. The addition of single doses of intramuscular amikacin and intravenously infused ceftriaxone to our prophylactic regimen of ciprofloxacin plus metronidazole resulted in a statistically significant reduction of infectious complications following TRUS Bx. PMID:28167960

  17. A double blind study of the effectiveness of sertaconazole 2% cream vs. metronidazole 1% gel in the treatment of seborrheic dermatitis.

    PubMed

    Goldust, Mohamad; Rezaee, Elham; Raghifar, Ramin

    2013-01-01

    Seborrheic dermatitis (SD) is generally treated with topical steroids, antifungals, or both. The aim of this study was to compare the efficacy of sertaconazole 2% cream vs. metronidazole 1% gel in the treatment of seborrheic dermatitis. A group of 156 patients suffering from SD were studied. The patients were randomly divided into two groups. The first group received local sertaconazole 2% cream and they were recommended to use the cream twice a day for 4 weeks. In the control group, thirty patients received metronidazole 1% gel twice a day for four weeks. At the point of referral, and also 2 and 4 weeks after the first visit, the patients were examined by a dermatologist to identify improvement of clinical symptoms. A higher level of satisfaction was observed after 28 days in the sertaconazole group (87.1%) than the metronidazole group (56.4%). Considering its efficacy, safety, and acceptability profiles, sertaconazole 2% cream is a worthwhile alternative to existing antifungal therapies for the treatment of seborrheic dermatitis.

  18. Botulism in metronidazole- treated conventional adult mice challenged orogastrically with spores of Clostridium botulinum type A or B.

    PubMed Central

    Wang, Y; Sugiyama, H

    1984-01-01

    Conventional adult mice were pretreated with metronidazole to make their intestinal tracts receptive to colonization by Clostridium botulinum. These mice, in groups of 10, were fed 0 (controls), 10(2), 10(3), 10(4), or 10(5) C. botulinum type B spores and were placed for observation in filter-lid cages whose screen floors minimized the amounts of feces available for coprophagy. The opportunity to eat feces was made equal for all mouse groups by placing one mouse of every group in each of 10 cages. Mice given a spore inoculum began to develop botulism after incubation periods of slightly less than 2.75 days. Morbidity rates, which reached maxima within 5 days of challenge, were related to inocula levels. Mortality rates were also dose related. Mice given 10(5) spores and then type B antitoxin intraperitoneally, a treatment not affecting intraintestinal toxin production, remained healthy. Morbidity among control mice was seldom more than 10% and could be ascribed to toxin ingested with feces. A C. botulinum type A spore suspension gave similar results, although morbidity and mortality rates were generally lower than after challenge with a comparable number of type B spores. Mice challenged with 10(2) or 10(5) spores had similar toxin levels in their large intestines 48 h later. Morbidity rates correlated better with toxin levels in the small intestines. PMID:6389360

  19. Extractional spectrophotometric analysis of metronidazole, tinidazole, ornidazole and secnidazole bases through acid-dye complexation using bromothymol blue dye.

    PubMed

    Darwish, Khaled M; Salama, Ismail; Mostafa, Samia; El-Sadek, Mohamed

    2012-01-01

    An easy, precise and valid extractional-spectrophotometric technique is described for the assessment of metronidazole (MNZ), tinidazole (TNZ), ornidazole (ONZ) and secnidazole (SNZ) in pure state and in their pharmaceutical formulations. The technique includes first the reduction of above cited drugs using HCl and zinc powder, then the formation of intense yellow colored ion-association complex species (1:3 drug/dye) using bromothymol blue (BTB) in a buffered aqueous acidic medium at pH 3-3.50. The colored products are extracted into dichloromethane and quantitatively determined at 416-420 nm. The experimental operating factors influencing the ion-pairs development were studied and optimized to obtain the maximum color intensity. The Beer plots are obeyed in the concentration ranges 2.50-22.50, 2.50-30, 7.50-35 and 5-30 μgml-1 for MNZ, TNZ, ONZ and SNZ, respectively, with correlation coefficients not less than 0.9995. The proposed technique is recommended for the routine quality control analysis of the investigated drugs in commercial tablets with no observed interference from common pharmaceutical adjuvants. Results of such analysis were statistically validated and through recovery studies, showing excellent agreement with those achieved by the reported techniques.

  20. Boron doped diamond sensor for sensitive determination of metronidazole: Mechanistic and analytical study by cyclic voltammetry and square wave voltammetry.

    PubMed

    Ammar, Hafedh Belhadj; Brahim, Mabrouk Ben; Abdelhédi, Ridha; Samet, Youssef

    2016-02-01

    The performance of boron-doped diamond (BDD) electrode for the detection of metronidazole (MTZ) as the most important drug of the group of 5-nitroimidazole was proven using cyclic voltammetry (CV) and square wave voltammetry (SWV) techniques. A comparison study between BDD, glassy carbon and silver electrodes on the electrochemical response was carried out. The process is pH-dependent. In neutral and alkaline media, one irreversible reduction peak related to the hydroxylamine derivative formation was registered, involving a total of four electrons. In acidic medium, a prepeak appears probably related to the adsorption affinity of hydroxylamine at the electrode surface. The BDD electrode showed higher sensitivity and reproducibility analytical response, compared with the other electrodes. The higher reduction peak current was registered at pH11. Under optimal conditions, a linear analytical curve was obtained for the MTZ concentration in the range of 0.2-4.2μmolL(-1), with a detection limit of 0.065μmolL(-1).

  1. Comparative artificial neural network and partial least squares models for analysis of Metronidazole, Diloxanide, Spiramycin and Cliquinol in pharmaceutical preparations.

    PubMed

    Elkhoudary, Mahmoud M; Abdel Salam, Randa A; Hadad, Ghada M

    2014-09-15

    Metronidazole (MNZ) is a widely used antibacterial and amoebicide drug. Therefore, it is important to develop a rapid and specific analytical method for the determination of MNZ in mixture with Spiramycin (SPY), Diloxanide (DIX) and Cliquinol (CLQ) in pharmaceutical preparations. This work describes simple, sensitive and reliable six multivariate calibration methods, namely linear and nonlinear artificial neural networks preceded by genetic algorithm (GA-ANN) and principle component analysis (PCA-ANN) as well as partial least squares (PLS) either alone or preceded by genetic algorithm (GA-PLS) for UV spectrophotometric determination of MNZ, SPY, DIX and CLQ in pharmaceutical preparations with no interference of pharmaceutical additives. The results manifest the problem of nonlinearity and how models like ANN can handle it. Analytical performance of these methods was statistically validated with respect to linearity, accuracy, precision and specificity. The developed methods indicate the ability of the previously mentioned multivariate calibration models to handle and solve UV spectra of the four components' mixtures using easy and widely used UV spectrophotometer.

  2. Comparative artificial neural network and partial least squares models for analysis of Metronidazole, Diloxanide, Spiramycin and Cliquinol in pharmaceutical preparations

    NASA Astrophysics Data System (ADS)

    Elkhoudary, Mahmoud M.; Abdel Salam, Randa A.; Hadad, Ghada M.

    2014-09-01

    Metronidazole (MNZ) is a widely used antibacterial and amoebicide drug. Therefore, it is important to develop a rapid and specific analytical method for the determination of MNZ in mixture with Spiramycin (SPY), Diloxanide (DIX) and Cliquinol (CLQ) in pharmaceutical preparations. This work describes simple, sensitive and reliable six multivariate calibration methods, namely linear and nonlinear artificial neural networks preceded by genetic algorithm (GA-ANN) and principle component analysis (PCA-ANN) as well as partial least squares (PLS) either alone or preceded by genetic algorithm (GA-PLS) for UV spectrophotometric determination of MNZ, SPY, DIX and CLQ in pharmaceutical preparations with no interference of pharmaceutical additives. The results manifest the problem of nonlinearity and how models like ANN can handle it. Analytical performance of these methods was statistically validated with respect to linearity, accuracy, precision and specificity. The developed methods indicate the ability of the previously mentioned multivariate calibration models to handle and solve UV spectra of the four components’ mixtures using easy and widely used UV spectrophotometer.

  3. Influence of metronidazole and some electron acceptors on the chlorin e6 photosensitized killing of Ehrlich carcinoma cells

    NASA Astrophysics Data System (ADS)

    Chekulayev, V.; Shevchuk, Igor; Mihkelsoo, Virgo T.; Kallikorm, A. P.

    1992-06-01

    A decrease in the effectiveness of photosensitized killing of neoplasm cells was observed in the presence of chlorin-e6 at a reduced concentration of oxygen. But when metronidazole (MZ) was injected in vitro as well as in vivo, a significant increase in the photosensitized killing of Ehrlich carcinoma cells by chlorin-e6 was observed. Moreover, contrary to the hematoporphyrin derivative (HpD), MZ increases the effectiveness of photodynamic therapy (PDT) by using chlorin-e6 not only in the hypoxic but also in the aerobic conditions. The interaction between MZ and the excited photosensitizer may account for an increased phototoxicity of chlorin-e6. The formation of cytotoxic nitroimidazole radicals as a result of photochemical processes of type 1 is discussed. This property of the photosensitizer may be successfully used in working out a method of potentiating PDT in combination not only with nitroimidazoles, but also with other electron acceptor compounds (EACp), e.g., quinone antitumor antibiotics.

  4. Therapeutic efficacies of Coriandrum sativum aqueous extract against metronidazole-induced genotoxicity in Channa punctatus peripheral erythrocytes.

    PubMed

    Talapatra, Soumendra Nath; Dasgupta, Subham; Guha, Gunjan; Auddy, Moumita; Mukhopadhyay, Aniruddha

    2010-12-01

    Metronidazole (MTZ), a nitroimidazole drug, is primarily used as an anti-protozoan or an anti-bacterial agent in humans, although its genotoxic and carcinogenic effects have been widely reported, particularly in aquatic organisms. MTZ may induce DNA damages through single-strand breaks, modification of bases, DNA-DNA and DNA-protein cross-links, ultimately leading to apoptosis or necrosis. Here, we have assessed the genotoxicity of MTZ in the peripheral erythrocytes of Channa punctatus, using micronucleation (MN) and binucleation (BN) as genotoxicity markers. The therapeutic potential of aqueous extract of Coriandrum sativum against MTZ-induced genotoxicity has also been examined. The results show significant (P<0.05) increase in both MN and BN formation due to MTZ treatment. Such aberrations were higher in smaller fish samples for a particular dosage of MTZ, as established by correlation analysis between fish body weight and MN/BN count at P<0.05. However, such degenerative damages were found to be alleviated by a great extent due to treatment with C. sativum leaf extract. Hence, we establish that MTZ can produce considerable degrees of micronucleus and binucleus formation in peripheral erythrocytes of C. punctatus, and such deleterious effect of MTZ treatment can be mitigated by aqueous extract of C. sativum leaves.

  5. Broad-spectrum Antibiotic Plus Metronidazole May Not Prevent the Deterioration of Necrotizing Enterocolitis From Stage II to III in Full-term and Near-term Infants: A Propensity Score-matched Cohort Study.

    PubMed

    Luo, Li-Juan; Li, Xin; Yang, Kai-Di; Lu, Jiang-Yi; Li, Lu-Quan

    2015-10-01

    Necrotizing enterocolitis (NEC) is the most common and frequently dangerous neonatal gastrointestinal disease. Studies have shown broad-spectrum antibiotics plus anaerobic antimicrobial therapy did not prevent the deterioration of NEC among very low birth preterm infants. However, few studies about this therapy which focused on full-term and near-term infant with NEC has been reported. The aim of this study was to evaluate the effect of broad-spectrum antibiotic plus metronidazole in preventing the deterioration of NEC from stage II to III in full-term and near-term infants.A retrospective cohort study based on the propensity score (PS) 1:1 matching was performed among the full-term and near-term infants with NEC (Bell stage ≥II). All infants who received broad-spectrum antibiotics were divided into 2 groups: group with metronidazole treatment (metronidazole was used ≥4 days continuously, 15 mg/kg/day) and group without metronidazole treatment. The depraved rates of stage II NEC between the 2 groups were compared. Meanwhile, the risk factors associated with the deterioration of stage II NEC were analyzed by case-control study in the PS-matched cases.A total of 229 infants met the inclusion criteria. Before PS-matching, we found the deterioration of NEC rate in the group with metronidazole treatment was higher than that in the group without metronidazole treatment (18.1% [28/155] vs 8.1% [6/74]; P = 0.048). After PS-matching, 73 pairs were matched, and the depraved rate of NEC in the group with metronidazole treatment was not lower than that in the group without metronidazole treatment (15.1% vs 8.2%; P = 0.2). Binary logistic regression analysis showed that sepsis after NEC (odds ratio [OR] 3.748, 95% confidence interval [CI] 1.171-11.998, P = 0.03), the need to use transfusion of blood products after diagnosis of NEC (OR 8.003, 95% CI 2.365-27.087, P = 0.00), and the need of longer time for nasogastric suction were risk factors for stage II NEC progressing to

  6. Evaluation of the in vitro activity of ceragenins against Trichomonas vaginalis.

    PubMed

    Polat, Zubeyde Akin; Cetin, Ali; Savage, Poul B

    2016-03-01

    Trichomonosis, caused by the protozoan parasite Trichomonas vaginalis, is a curable sexually transmitted disease that is most commonly encountered worldwide. Increasing importance of trichomoniasis and emerging of resistance against metronidazole lead to search for alternative drugs with different mode of activity. The purpose of this study was to determine in vitro activity of ceragenins (CSA-13, CSA-44, CSA-13, and CSA-138) against the metronidazole-susceptible (ATCC 30001) and metronidazole-resistant (ATCC 50138) strains of T. vaginalis. The effective concentrations were evaluated using two strains of T. vaginalis with different metronidazole susceptibilities (ATCC 30001 and ATCC 50138) in the presence of dilution series of ceragenins in 24-well microtitre assays. Overall, all the ceragenins killed the metronidazole-susceptible (ATCC 30001) and metronidazole-resistant (ATCC 50138) strains of T. vaginalis (p>0.05). With regard to the their effects against the studied strains of T. vaginalis, in order of effectiveness, overall, the ceragenins ordered as CSA-13 (the most effective), CSA-131 and CSA-138 (effective similarly), and CSA-44 (the least effective) (p<0.05). All of the ceragenins reduced the trophozoite numbers of both of studied strains of T. vaginalis with a time- and dose- dependent manner (p<0.05). Although all of the study ceragenins, CSA-13, CSA-44, CSA-13, and CSA-138, killed the studied strains of T. vaginalis. CSA-13 is the leading ceragenin as the most effective anti-trichomonas compound, followed by CSA-131 and CSA-138. They have a potential to have a place in the armemantarium of gynecologic and urologic practice for the management of sexually transmitted diseases.

  7. A randomized, double-blind study comparing Clostridium difficile immune whey and metronidazole for recurrent Clostridium difficile-associated diarrhoea: efficacy and safety data of a prematurely interrupted trial.

    PubMed

    Mattila, Eero; Anttila, Veli-Jukka; Broas, Markku; Marttila, Harri; Poukka, Paula; Kuusisto, Kaisa; Pusa, Liana; Sammalkorpi, Kari; Dabek, Jan; Koivurova, Olli-Pekka; Vähätalo, Markku; Moilanen, Veikko; Widenius, Tom

    2008-01-01

    A prospective, randomized, double-blind study was designed to compare Clostridium difficile immune whey (CDIW) with metronidazole for treatment of laboratory-confirmed, recurrent, mild to moderate episodes of Clostridium difficile-associated diarrhoea (CDAD). CDIW was manufactured by immunization of cows in their gestation period with inactivated C. difficile vaccine. The resulting colostrum was processed, immunoglubulins were concentrated and the end-product containing high titres of C. difficile immunoglobulin was used as CDIW. 20 patients received metronidazole at a dosage of 400 mg t.i.d. and 18 patients CDIW 200 ml t.i.d. The study was interrupted early because of the bankruptcy of the sponsor. After 14 d of treatment, all 20 (100%) of 20 patients had responded to metronidazole therapy, compared with 16 (89%) of 18 who had received CDIW. 70 d after the beginning of treatment, sustained responses were observed in 11 (55%) of 20 patients receiving metronidazole and 10 (56%) of 18 patients treated with CDIW. In this preliminary study CDIW was as effective as metronidazole in the prevention of CDAD recurrences and it was well tolerated.

  8. Surface Deposition and Coalescence and Coacervation Phase Separation Methods: In Vitro Study and Compatibility Analysis of Eudragit RS30D, Eudragit RL30D, and Carbopol-PLA Loaded Metronidazole Microspheres

    PubMed Central

    Dewan, Irin; Islam, Md. Maynul; Al-Hasan, Maksud; Nath, Joydeb; Sultana, Sefat; Rana, Md. Sohel

    2015-01-01

    Metronidazole (MTZ) has extremely broad spectrum of protozoal and antimicrobial activity and is clinically effective in trichomoniasis, amoebic colitis, and giardiasis. This study was performed to formulate and evaluate the MTZ loaded microspheres by coacervation phase separation and surface deposition and coalescence methods using different polymers like Gelatin, Carbopol 934P, Polylactic Acid (PLA), Eudragit RS30D, and Eudragit RL30D to acquire sustained release of drug. In vitro dissolution studies were carried out in phosphate buffer (pH 7.4) for 8 hours according to USP paddle method. The maximum and minimum release of MTZ from microspheres observed were 84.81% and 76.6% for coacervation and 95.07% and 80.07% for surface deposition method, respectively, after 8 hours. Release kinetics was studied in different mathematical release models. The SEM and FTIR studies confirm good spheres and smooth surface as well as interaction between drug and polymers. Though release kinetic is uncertain, the best fit was obtained with the Korsmeyer kinetic model with release exponent (n) lying between 0.45 and 0.89. In vitro studies showed that MTZ microspheres with different polymers might be a good candidate as sustained drug delivery system to treat bacterial infections. PMID:26649228

  9. Synthesis of magnetic molecularly imprinted polymers for the selective separation and determination of metronidazole in cosmetic samples.

    PubMed

    Liu, Min; Li, Xiao-Yan; Li, Jun-Jie; Su, Xiao-Meng; Wu, Zong-Yuan; Li, Peng-Fei; Lei, Fu-Hou; Tan, Xue-Cai; Shi, Zhan-Wang

    2015-05-01

    In this study, novel magnetic molecularly imprinted polymers (MMIPs) were developed as a sorbent for solid-phase extraction (SPE) and used for the selective separation of metronidazole (MNZ) in cosmetics; MNZ was detected by high-performance liquid chromatography (HPLC). First, magnetic Fe3O4 nanoparticles (NPs) were prepared by the co-precipitation of Fe(2+)and Fe(3+) ions in an ammonia solution; then oleic acid (OA) was modified onto the surface of Fe3O4NPs. Finally, the MMIP was prepared by aqueous suspension polymerization, involving the copolymerization of Fe3O4NPs@OA with MNZ as the template molecule, methacrylic acid (MAA) as the functional monomer, ethylene glycol maleic rosinate acrylate (EGMRA) as the cross-linking agent, and 2,2-azobisisobutyronitrile (AIBN) as the initiator. The MMIP materials showed high selective adsorption capacity and fast binding kinetics for MNZ; the maximum adsorption amount of the MMIP to MNZ was 46.7 mg/g. The assay showed a linear range from 0.1 to 20.0 μg/mL for MNZ with the correlation coefficient 0.999. The relative standard deviations (RSD) of intra- and inter-day ranging from 0.71 to 2.45% and from 1.06 to 5.20% were obtained. The MMIP can be applied to the enrichment and determination of MNZ in cosmetic products with the recoveries of spiked toner, powder, and cream cosmetic samples ranging from 90.6 to 104.2, 84.1 to 91.4, and 90.3 to 100.4%, respectively, and the RSD was <3.54%.

  10. Simultaneous multiresidue determination of metronidazole and spiramycin in fish muscle using high performance liquid chromatography with UV detection.

    PubMed

    Maher, Hadir M; Youssef, Rasha M; Khalil, Riad H; El-Bahr, Sabry M

    2008-12-15

    An efficient multiresidue method for the simultaneous determination of metronidazole (MET) and spiramycin (SPY) in tilapia fish muscle, based on high performance liquid chromatography with UV detection (HPLC-UV), has been developed. The drugs were extracted with 0.2% orthophosphoric acid-methanol (6:4), and the extracts were cleaned up on a solid phase extraction cartridge, C18 Sep-Pak light column. The LC separation was performed on a RP stainless-steel C-18 analytical column (150 mm x 4.6 mm, 5 microm) with a gradient elution system of 0.05 M phosphate buffer adjusted to pH 2.4-acetonitrile as the mobile phase at the flow rate of 1.0 ml min(-1). A wavelength programming was applied for the UV detection of the analytes. The method not only enabled the determination of the parent drugs, MET and SPY, but also permitted the determination of their metabolites, hydroxymetronidazole (HMET) and neospiramycin (NSPY). The calibration graphs for each drug were rectilinear in the range of 0.005-1.000 microg g(-1) for MET and HMET and 0.025-1.000 microg g(-1) for SPY and NSPY. With this method, the cited drugs with their metabolites were determined in fortified fish muscle tissues at levels of 0.025, 0.1 and 1.0 microg g(-1) with good accuracy and precision. LOD and LOQ obtained for each drug were as follows: 0.002 and 0.005 microg g(-1) for MET and HMET and 0.005 and 0.025 microg g(-1) for SPY and NSPY. Utilization of the method to successfully analyze tilapia fish muscle samples incurred with MET and SPY was described.

  11. Development and Optimization of HPLC Analysis of Metronidazole, Diloxanide, Spiramycin and Cliquinol in Pharmaceutical Dosage Forms Using Experimental Design.

    PubMed

    Elkhoudary, Mahmoud M; Abdel Salam, Randa A; Hadad, Ghada M

    2016-11-01

    A new simple, sensitive, rapid and accurate gradient reversed-phase high-performance liquid chromatography with photodiode array detector (RP-HPLC-DAD) was developed and validated for simultaneous analysis of Metronidazole (MNZ), Spiramycin (SPY), Diloxanidefuroate (DIX) and Cliquinol (CLQ) using statistical experimental design. Initially, a resolution V fractional factorial design was used in order to screen five independent factors: the column temperature (°C), pH, phosphate buffer concentration (mM), flow rate (ml/min) and the initial fraction of mobile phase B (%). pH, flow rate and initial fraction of mobile phase B were identified as significant, using analysis of variance. The optimum conditions of separation determined with the aid of central composite design were: (1) initial mobile phase concentration: phosphate buffer/methanol (50/50, v/v), (2) phosphate buffer concentration (50 mM), (3) pH (4.72), (4) column temperature 30°C and (5) mobile phase flow rate (0.8 ml min(-1)). Excellent linearity was observed for all of the standard calibration curves, and the correlation coefficients were above 0.9999. Limits of detection for all of the analyzed compounds ranged between 0.02 and 0.11 μg ml(-1); limits of quantitation ranged between 0.06 and 0.33 μg ml(-1) The proposed method showed good prediction ability. The optimized method was validated according to ICH guidelines. Three commercially available tablets were analyzed showing good % recovery and %RSD.

  12. Efficacy and safety of metronidazole injection for the treatment of infectious peritonitis, abdominal abscess and pelvic inflammatory diseases in Japan.

    PubMed

    Mikamo, Hiroshige; Matsumizu, Miyako; Nakazuru, Yoshiomi; Nagashima, Masahito

    2015-02-01

    Although metronidazole (MNZ) has been used worldwide for more than 4 decades as a standard therapy for trichomoniasis, anaerobic and amebic infections, resistance to MNZ is still low. MNZ is available as oral, intravenous, and vaginal formulations, but the intravenous formulation of MNZ has not been approved in Japan. We conducted a phase 3 study to evaluate the efficacy and safety of intravenous MNZ combined with ceftriaxone (CTRX) in Japanese subjects with infectious peritonitis, abdominal abscess or pelvic inflammatory diseases (PIDs) to obtain regulatory approval. A combination of MNZ/CTRX at doses of 500 mg 3 or 4 times a day/1 or 2 g twice a day was administered intravenously to a total of 38 hospitalized subjects. MNZ/CTRX was well tolerated and exhibited excellent clinical and bacteriological efficacy with clinical efficacy rates of 100% (20/20) in infectious peritonitis or abdominal abscess subjects and 90.0% (9/10) in PID subjects, and the eradication rates in infectious peritonitis or abdominal abscess subjects and PID subjects were 100% (16/16) and 100% (4/4), respectively, at the test of cure. MNZ/CTRX was effective in 1 subject in whom a metallo-β-lactamase-producing Bacteroides fragilis strain (MIC of MNZ, 2 μg/ml) was identified. The most common treatment-related adverse event was diarrhea (23.7%), followed by nausea (5.3%). No new safety signals were identified. MNZ/CTRX demonstrated excellent efficacy and was well tolerated in Japanese infectious peritonitis, abdominal abscess and PID subjects. This treatment regimen can be useful for anaerobic infections. Clinical registration number: NCT01473836.

  13. Effect of ageing of human serum albumin in vitro on surface hydrophobicity and binding sites of metronidazole

    NASA Astrophysics Data System (ADS)

    Równicka-Zubik, J.; Sułkowska, A.; Dubas, M.; Pożycka, J.; Maciążek-Jurczyk, M.; Bojko, B.; Sułkowski, W. W.

    2011-05-01

    The fluorescence characteristic of the "alkaline-ageing" process was performed. The quenching of the aged form of human serum albumin (AHSA) fluorescence by acrylamide (Ac) was smaller than that of native HSA, in contrast to the negatively charged anion iodide quencher. The comparison of quenching of fluorescence probes ANS and DNSA bound to aged and native forms of HSA allows for the conclusion that "alkaline-ageing process" causes an increase of hydrophobicity within the binding site located in subdomain IIA. This conclusion was confirmed by the F coefficients calculated for the emission fluorescence spectra of A- and N-forms of HSA excited at 295 nm and 275 nm which show that the increase of hydrophobicity is more significant within tyrosyl than within tryptophanyl residues. The binding constants metronidazole-HSA as well as the number of the class of binding sites were determined by the use of the Scatchard and Klotz-plot analysis. Ageing of HSA causes an increase of the quenching constant determined from the Stern-Volmer equation for λex 275 nm. However ageing does not affect the K Q value for λex 295 nm. The influence of ageing of human serum albumin on its surface hydrophobicity was also studied with the use of 8-anilino-1-naphthalenesulfonic acid (ANS) as the fluorescence probe. At the ANS fluorescence excitation wavelength λex 360 nm the change in surface hydrophobicity is not observed for both N- and A-forms of HSA. The increase of surface hydrophobicity of the A-form in comparison with that of the native form at λex 295 nm indicates that within subdomain IIA an alteration of HSA conformation takes place.

  14. Impact of metronidazole and amoxicillin combination on matrix metalloproteinases-1 and tissue inhibitors of matrix metalloproteinases balance in generalized aggressive periodontitis

    PubMed Central

    Cifcibasi, Emine; Kantarci, Alpdogan; Badur, Selim; Issever, Halim; Cintan, Serdar

    2015-01-01

    Objective: Generalized aggressive periodontitis (GAgP) is a complex periodontal disease affecting the entire dentition with a rapid destruction of the periodontium and resulting in loss of teeth. We hypothesized that better clinical healing of adjunctive use of amoxicillin plus metronidazole combination may be related to the effect of this combination therapy to restore imbalance between matrix metalloproteinases (MMP) and their tissue inhibitors (TIMP) which is associated with connective tissue and alveolar bone destruction in patients with GAgP. Materials and Methods: Twenty-eight subjects diagnosed with GAgP were recruited. Patients were randomly assigned to test or control groups. MMP-1/TIMP-1 ratio was compared between groups receiving scaling and root planning (SRP) alone (control) or in combination with amoxicillin plus metronidazole (test). Clinical periodontal variables were measured. Gingival crevicular fluid samples were obtained and analyzed for MMP-1 and TIMP-1. Measurements were taken at baseline and repeated at 3 and 6 months after therapy. Results: Total MMP-1 levels were significantly decreased in both groups (P < 0.05) at 3 and 6 months. MMP-1 concentration levels showed a similar pattern to MMP-1 total levels decreasing significantly at 3 months (P < 0.05). TIMP-1 concentration levels increased in the test group throughout the study period, while the difference did not reach statistical significance (P > 0.05). TIMP-1/MMP-1 balance was restored in test group at 6 months significantly better than the control group (P < 0.05). Conclusion: The results of this study suggest that metronidazole and amoxicillin combination as an adjunct to SRP results in better clinical healing through restoring TIMP-1/MMP-1 balance. PMID:25713485

  15. An investigation and characterization on alginate hydogel dressing loaded with metronidazole prepared by combined inotropic gelation and freeze-thawing cycles for controlled release.

    PubMed

    Sarheed, Omar; Rasool, Bazigha K Abdul; Abu-Gharbieh, Eman; Aziz, Uday Sajad

    2015-06-01

    The purpose of this study was to investigate the effect of combined Ca(2+) cross-linking and freeze-thawing cycle method on metronidazole (model drug) drug release and prepare a wound film dressing with improved swelling property. The hydrogel films were prepared with sodium alginate (SA) using the freeze-thawing method alone or in combination with ionotropic gelation with CaCl2. The gel properties such as morphology, swelling, film thickness, and content uniformity and in vitro dissolution profiles using Franz diffusion cell were investigated. The cross-linking process was confirmed by differential scanning calorimetry (DSC) and Fourier transform infrared (FTIR) spectroscopy. In vitro protein adsorption test, in vivo wound-healing test, and histopathology were also performed. The hydrogel (F2) composed of 6% sodium alginate and 1% metronidazole prepared by combined Ca(2+) cross-linking and freeze-thawing cycles showed good swelling. This will help to provide moist environment at the wound site. With the in vivo wound-healing and histological studies, F2 was found to improve the wound-healing effect compared with the hydrogel without the drug, and the conventional product.

  16. Effects of drying methods on the physicochemical and compressional characteristics of Okra powder and the release properties of its metronidazole tablet formulation.

    PubMed

    Bakre, L G; Jaiyeoba, K T

    2009-02-01

    A study has been made of the effects of sun and oven drying methods on the physicochemical characteristics and compressibility of Okra powder and the release properties of its metronidazole tablet formulation. Corn starch was used as the reference standard. The mechanical properties of the tablets were evaluated using crushing strength and friability, while the release properties were determined using the disintegration times and dissolution rates. The results obtained showed that sun-dried Okra powder had smaller particle size, exhibited good flow and possessed higher hydration and swelling capacities compared to the oven dried samples. The compressibility of Okra powders assessed by the indices of plasticity from Heckel (Py) and Kawakita plots (Pk) showed that sun dried Okra powders had higher Py but lower Pk values than the oven-dried Okra powder. Metronidazole tablets formulated with oven dried Okra powder formed stronger tablets than tablets containing sun dried Okra powder. Generally, tablets containing sun dried Okra powders had faster disintegration and dissolution than tablets formulated with oven-dried powder. The results suggest that the choice of drying method during the processing of pharmaceutical raw materials is critical to its physicochemical properties and the release properties of its tablet formulations.

  17. Randomized Trial of Periodic Presumptive Treatment With High-Dose Intravaginal Metronidazole and Miconazole to Prevent Vaginal Infections in HIV-negative Women

    PubMed Central

    McClelland, R. Scott; Balkus, Jennifer E.; Lee, Jeannette; Anzala, Omu; Kimani, Joshua; Schwebke, Jane; Bragg, Vivian; Lensing, Shelly; Kavak, Lale

    2015-01-01

    Background. Vaginal infections are common, frequently recur, and may increase women's risk for sexually transmitted infections (STIs). We tested the efficacy of a novel regimen to prevent recurrent vaginal infections. Methods. Human immunodeficiency virus (HIV)–negative women 18–45 years old with 1 or more vaginal infections, including bacterial vaginosis (BV), vulvovaginal candidiasis (VVC), or Trichomonas vaginalis (TV), were randomly assigned to receive vaginal suppositories containing metronidazole 750 mg plus miconazole 200 mg or matching placebo for 5 consecutive nights each month for 12 months. Primary endpoints, evaluated every 2 months, were BV (Gram stain) and VVC (positive wet mount and culture). Results. Participants (N = 234) were randomly assigned to the intervention (N = 118) or placebo (N = 116) arm. Two hundred seventeen (93%) women completed an end-of-study evaluation. The intervention reduced the proportion of visits with BV compared to placebo (21.2% vs 32.5%; relative risk [RR] 0.65, 95% confidence interval [CI] .48–.87). In contrast, the proportion of visits with VVC was similar in the intervention (10.4%) versus placebo (11.3%) arms (RR 0.92, 95% CI .62–1.37). Conclusions. Monthly treatment with intravaginal metronidazole plus miconazole reduced the proportion of visits with BV during 12 months of follow-up. Further study will be important to determine whether this intervention can reduce women's risk of STIs. PMID:25526757

  18. Evaluation of Giardia lamblia thioredoxin reductase as drug activating enzyme and as drug target.

    PubMed

    Leitsch, David; Müller, Joachim; Müller, Norbert

    2016-12-01

    The antioxidative enzyme thioredoxin reductase (TrxR) has been suggested to be a drug target in several pathogens, including the protist parasite Giardia lamblia. TrxR is also believed to catalyse the reduction of nitro drugs, e.g. metronidazole and furazolidone, a reaction required to render these compounds toxic to G. lamblia and other microaerophiles/anaerobes. It was the objective of this study to assess the potential of TrxR as a drug target in G. lamblia and to find direct evidence for the role of this enzyme in the activation of metronidazole and other nitro drugs. TrxR was overexpressed approximately 10-fold in G. lamblia WB C6 cells by placing the trxR gene behind the arginine deiminase (ADI) promoter on a plasmid. Likewise, a mutant TrxR with a defective disulphide reductase catalytic site was strongly expressed in another G. lamblia WB C6 cell line. Susceptibilities to five antigiardial drugs, i.e. metronidazole, furazolidone, nitazoxanide, albendazole and auranofin were determined in both transfectant cell lines and compared to wildtype. Further, the impact of all five drugs on TrxR activity in vivo was measured. Overexpression of TrxR rendered G. lamblia WB C6 more susceptible to metronidazole and furazolidone but not to nitazoxanide, albendazole, and auranofin. Of all five drugs tested, only auranofin had an appreciably negative effect on TrxR activity in vivo, albeit to a much smaller extent than expected. Overexpression of TrxR and mutant TrxR had hardly any impact on growth of G. lamblia WB C6, although the enzyme also exerts a strong NADPH oxidase activity which is a source of oxidative stress. Our results constitute first direct evidence for the notion that TrxR is an activator of metronidazole and furazolidone but rather question that it is a relevant drug target of presently used antigiardial drugs.

  19. In vitro genotoxicity of neutral red after photo-activation and metabolic activation in the Ames test, the micronucleus test and the comet assay.

    PubMed

    Guérard, Melanie; Zeller, Andreas; Singer, Thomas; Gocke, Elmar

    2012-07-04

    Neutral red (Nr) is relatively non-toxic and is widely used as indicator dye in many biological test systems. It absorbs visible light and is known to act as a photosensitizer, involving the generation of reactive oxygen species (type-I reaction) and singlet oxygen (type-II reaction). The mutagenicity of Nr was determined in the Ames test (with Salmonella typhimurium strains TA1535, TA97, TA98, TA98NR, TA100, and TA102) with and without metabolic activation, and with and without photo-activation on agar plates. Similarly to the situation following metabolic activation, photo-mutagenicity of Nr was seen with all Salmonella strains tested, albeit with different effects between these strains. To our knowledge, Nr is the only photo-mutagen showing such a broad action. Since the effects are also observed in strains not known to be responsive to ROS, this indicates that ROS production is not the sole mode of action that leads to photo-genotoxicity. The reactive species produced by irradiation are short-lived as pre-irradiation of an Nr solution did not produce mutagenic effects when added to the bacteria. In addition, mutagenicity in TA98 following irradiation was stronger than in the nitroreductase-deficient strain TA98NR, indicating that nitro derivatives that are transformed by bacterial nitroreductase to hydroxylamines appear to play a role in the photo-mutagenicity of Nr. Photo-genotoxicity of Nr was further investigated in the comet assay and micronucleus test in L5178Y cells. Concentration-dependent increases in primary DNA damage and in the frequency of micronuclei were observed after irradiation.

  20. Comparison of the Effect of Vaginal Zataria multiflora Cream and Oral Metronidazole Pill on Results of Treatments for Vaginal Infections including Trichomoniasis and Bacterial Vaginosis in Women of Reproductive Age.

    PubMed

    Abdali, Khadijeh; Jahed, Leila; Amooee, Sedigheh; Zarshenas, Mahnaz; Tabatabaee, Hamidreza; Bekhradi, Reza

    2015-01-01

    Effect of Zataria multiflora on bacterial vaginosis and Trichomonas vaginalis is shown in vivo and in vitro. We compare the effectiveness of Zataria multiflora cream and oral metronidazole pill on results of treatment for vaginal infections including Trichomonas and bacterial vaginosis; these infections occur simultaneously. The study included 420 women with bacterial vaginosis, Trichomonas vaginalis, or both infections together, who were randomly divided into six groups. Criteria for diagnosis were wet smear and Gram stain. Vaginal Zataria multiflora cream and placebo pill were administered to the experiment groups; the control group received oral metronidazole pill and vaginal placebo cream. Comparison of the clinical symptoms showed no significant difference in all three vaginitis groups receiving metronidazole pill and vaginal Zataria multiflora cream. However, comparison of the wet smear test results was significant in patients with trichomoniasis and bacterial vaginosis associated with trichomoniasis in the two treatment groups (p = 0.001 and p = 0.01). Vaginal Zataria multiflora cream had the same effect of oral metronidazole tablets in improving clinical symptoms of all three vaginitis groups, as well as the treatment for bacterial vaginosis. It can be used as a drug for treatment of bacterial vaginosis and elimination of clinical symptoms of Trichomonas vaginitis.

  1. Comparison of the Effect of Vaginal Zataria multiflora Cream and Oral Metronidazole Pill on Results of Treatments for Vaginal Infections including Trichomoniasis and Bacterial Vaginosis in Women of Reproductive Age

    PubMed Central

    Abdali, Khadijeh; Jahed, Leila; Amooee, Sedigheh; Zarshenas, Mahnaz; Tabatabaee, Hamidreza; Bekhradi, Reza

    2015-01-01

    Effect of Zataria multiflora on bacterial vaginosis and Trichomonas vaginalis is shown in vivo and in vitro. We compare the effectiveness of Zataria multiflora cream and oral metronidazole pill on results of treatment for vaginal infections including Trichomonas and bacterial vaginosis; these infections occur simultaneously. The study included 420 women with bacterial vaginosis, Trichomonas vaginalis, or both infections together, who were randomly divided into six groups. Criteria for diagnosis were wet smear and Gram stain. Vaginal Zataria multiflora cream and placebo pill were administered to the experiment groups; the control group received oral metronidazole pill and vaginal placebo cream. Comparison of the clinical symptoms showed no significant difference in all three vaginitis groups receiving metronidazole pill and vaginal Zataria multiflora cream. However, comparison of the wet smear test results was significant in patients with trichomoniasis and bacterial vaginosis associated with trichomoniasis in the two treatment groups (p = 0.001 and p = 0.01). Vaginal Zataria multiflora cream had the same effect of oral metronidazole tablets in improving clinical symptoms of all three vaginitis groups, as well as the treatment for bacterial vaginosis. It can be used as a drug for treatment of bacterial vaginosis and elimination of clinical symptoms of Trichomonas vaginitis. PMID:26266260

  2. Bismuth, Metronidazole, and Tetracycline

    MedlinePlus

    ... Talk to your pharmacist or contact your local garbage/recycling department to learn about take-back programs in your community. See the FDA's Safe Disposal of Medicines website (http://goo.gl/c4Rm4p) for ...

  3. Antibacterial activities of nitrothiazole against Campylobacter jejuni and Campylobacter coli.

    PubMed Central

    Hof, H; Rieffert, M; Sticht-Groh, V; Zak, O; Schweizer, E H

    1984-01-01

    Niridazole (Ambilhar) and three other newly synthesized nitrothiazole derivatives were highly active against 19 microaerophilic campylobacters (minimum concentration required to inhibit 50% of strains [MIC50], 0.0075 to 0.015 mg/liter). There were, however, considerable differences in the susceptibility among strains tested, and one nitrothiazole derivative was rather inactive (MIC50, 2 mg/liter). Nitroimidazole derivatives, such as metronidazole and tinidazole, were less active (MIC50, 2 and 4 mg/liter, respectively). The nitrofuran derivatives, such as nitrofurazone and nitrofurantoin, were also less active (MIC50, 1 mg/liter). Niridazole and another potent nitrothiazole derivative killed the campylobacters rapidly at low concentrations. In contrast, much higher concentrations of metronidazole were required to achieve bactericidal values. PMID:6517542

  4. ["In vitro" susceptibility of some aerobic and anaerobic bacteria to three 5-nitro-imidazole derivatives: metronidazole, ornidazole and tinidazole (author's transl)].

    PubMed

    Dublanchet, A; Durieux, R

    1980-01-01

    As shown earlier, the three drugs are effective against most anaerobic bacteria. However, with Bacteroides fragilis the geometric mean MIC of metronidazole (0.43 microgram/ml), ornidazole (0.37 microgram/ml) and tinidazole (0.20 microgram/ml) are statistically different. Moreover, and contrary to generally accepted opinion, some aerobic bacteria such as Moraxella and Bacillus can be susceptible to nitro-imidazoles. The results suggest another mechanism for the action of nitro-imidazoles, different from that previously described. This underscores the major role of the reduction of the nitrogroup by a low-redox-potential. Two strains of strictly anaerobic bacteria show a relative resistance in the microaerophilic zone.

  5. Spectroscopic investigation on assisted sonocatalytic damage of bovine serum albumin (BSA) by metronidazole (MTZ) under ultrasonic irradiation combined with nano-sized ZnO.

    PubMed

    Gao, Jingqun; Liu, Bin; Wang, Jun; Jin, Xudong; Jiang, Renzheng; Liu, Lijun; Wang, Baoxin; Xu, Yongnan

    2010-11-01

    The previous work proved that the bovine serum albumin (BSA) could be damaged under the combined action of ultrasonic irradiation and ZnO. In this work, the assisted sonocatalytic damage of BSA using metronidazole (MTZ) as a sensitizer was further investigated by means of UV-vis and fluorescence spectra. The results indicated that the adding of MTZ could obviously promote the sonocatalytic damage of BSA under ultrasonic irradiation in the presence of nano-sized ZnO powder. Furthermore, it was found that the damage degree of BSA was aggravated by some influencing factors except ionic kind and strength. In addition, the damage site of BSA was also studied with synchronous fluorescence technology. It was found that the damage site was mainly at tryptophan (Trp) residue.

  6. Catalytic damage of bovine serum albumin by metronidazole under ultrasonic irradiation in the presence of nano-sized TiO2 powder

    NASA Astrophysics Data System (ADS)

    Wang, J.; Wang, Z. G.; Jin, X. D.; Guo, Y. W.; Gao, J. Q.; Li, K.; Wang, B. X.; Li, Y.

    2012-05-01

    In previous work, it was found that the bovine serum albumin (BSA) could obviously be damaged by nano-sized TiO2 powder as a sonocatalyst under ultrasonic irradiation. In this work, metronidazole (MTZ) was adopted as a sensitizer to intensify the damage of BSA molecules. It was found that the damage degree of BSA molecules in the presence of MTZ was more serious than in the absence of MTZ. That is, under ultrasonic irradiation combined with nano-sized TiO2 powder, the addition of MTZ could remarkably aggravate the damage to BSA molecules. Meanwhile, the damage degree was also affected by some influence factors, such as ultrasonic irradiation time, ultrasonic irradiation power, MTZ concentration, solution acidity, ionic strength and solution temperature. In addition, the damage site of BSA molecules was also estimated by synchronous fluorescence spectra. It was found that the damage site of BSA molecules was mainly at tyrosine (Tyr) residue.

  7. Spectroscopic investigation on assisted sonocatalytic damage of bovine serum albumin (BSA) by metronidazole (MTZ) under ultrasonic irradiation combined with nano-sized ZnO

    NASA Astrophysics Data System (ADS)

    Gao, Jingqun; Liu, Bin; Wang, Jun; Jin, Xudong; Jiang, Renzheng; Liu, Lijun; Wang, Baoxin; Xu, Yongnan

    2010-11-01

    The previous work proved that the bovine serum albumin (BSA) could be damaged under the combined action of ultrasonic irradiation and ZnO. In this work, the assisted sonocatalytic damage of BSA using metronidazole (MTZ) as a sensitizer was further investigated by means of UV-vis and fluorescence spectra. The results indicated that the adding of MTZ could obviously promote the sonocatalytic damage of BSA under ultrasonic irradiation in the presence of nano-sized ZnO powder. Furthermore, it was found that the damage degree of BSA was aggravated by some influencing factors except ionic kind and strength. In addition, the damage site of BSA was also studied with synchronous fluorescence technology. It was found that the damage site was mainly at tryptophan (Trp) residue.

  8. Anti-Trichomonas vaginalis activity of betulinic acid derivatives.

    PubMed

    Hübner, Dariana Pimentel Gomes; de Brum Vieira, Patrícia; Frasson, Amanda Piccoli; Menezes, Camila Braz; Senger, Franciane Rios; Santos da Silva, Gloria Narjara; Baggio Gnoatto, Simone Cristina; Tasca, Tiana

    2016-12-01

    Caused by Trichomonas vaginalis, trichomoniasis is the most common non-viral STD worldwide. Currently, metronidazole and tinidazole are the only drugs approved for treatment of the condition. However, problems such as metronidazole-resistant T. vaginalis isolates and allergic reactions have been reported. Based on data previously published by our group, structural changes in betulinic acid (1) were performed, generating three new compounds that were tested for in vitro anti-T.vaginalis activity in this study. Whereas derivative 2 did not demonstrate anti-T. vaginalis activity, derivatives 3 and 4 reduced trophozoite viability by 100%, with MIC values of 50μM. The structural difference of two compounds was performed only on the C-28 position. Derivative 3 showed low cytotoxicity against Vero cells in 24h; however, derivative 4 was highly cytotoxic, but efficient when associated with metronidazole in the synergism assay. ROS production by neutrophils was reduced, and derivative 3 showed anti-inflammatory effect. Collectively, the results of this study provide in vitro evidence that betulinic acid derivatives 3 and 4 are potential compounds with anti-T. vaginalis activity.

  9. Antianaerobic Activity of Sulopenem Compared to Six Other Agents ▿

    PubMed Central

    Ednie, Lois M.; Appelbaum, Peter C.

    2009-01-01

    Agar dilution MIC methodology was used to compare the activity of sulopenem with those of amoxicillin/clavulanate, ampicillin/sulbactam, piperacillin-tazobactam, imipenem, clindamycin, and metronidazole against 431 anaerobes. Overall, MIC50/90 values were as follows: sulopenem, 0.25/1.0 μg/ml; amoxicillin/clavulanate, 0.5/2.0 μg/ml; ampicillin/sulbactam, 0.5/4.0 μg/ml; piperacillin/tazobactam, 0.25/8.0 μg/ml; imipenem, 0.06/1.0 μg/ml; clindamycin, 0.25/16.0 μg/ml; and metronidazole, 1.0/4.0 μg/ml. PMID:19223615

  10. [Antimicrobial activity of ornidazole and 6 other antibiotics against anaerobic bacteria].

    PubMed

    Alados, J C; Martínez-Brocal, A; Miranda, C; Rojo, M D; García, V; Domínguez, M C; de la Rosa, M

    1991-04-01

    The antimicrobial susceptibility of 235 anaerobic bacterial strains to ornidazole, metronidazole, chloramphenicol, clindamycin, penicillin, cefoxitin and imipenem has been studied using agar-dilution technique. Ornidazole and metronidazole were active against 88.6% and 86% of gram-positive cocci. Overall, 99.1% of Bacteroides group fragilis, and 91.3% of non-fragilis Bacteroides were also sensitive to both drugs. We did not find any Clostridium perfringens resistant strain. Cefoxitin and penicillin showed good activity against all Clostridium perfringens strains, and also against 97.7% and 92.5% of gram-positive cocci. We found one single imipenem resistant strain among gram-positive bacteria. Bacteroides fragilis also showed sensitivity to penicillin (41.5%), cefoxitin (85.7%) and imipenem (97.1%). Clindamycin was active against Clostridium perfringens (90.9%), gram-positive cocci (86.7%) and imipenem (68.6%). Chloramphenicol showed good activity against Clostridium perfringens (100%), gram-positive cocci (95.5%) and Bacteroides spp. (99.4%). Our results showed an overall good activity of all the seven drugs tested against anaerobic gram-positive microorganisms. Of notice, we found a good activity of chloramphenicol, imipenem, metronidazole and ornidazole against Bacteroides spp.

  11. Effects of the antibacterial agents tiamulin, olanquindox and metronidazole and the anthelmintic ivermectin on the soil invertebrate species Folsomia fimetaria (Collembola) and Enchytraeus crypticus (Enchytraeidae).

    PubMed

    Jensen, John; Krogh, Paul Henning; Sverdrup, Line E

    2003-01-01

    Veterinary pharmaceutical products such as antibacterial agents and antiparasitics are widely used to control diseases and promote production in the agricultural sector. Exposure of non-target organisms are a likely result of using manure from treated live stocks or from dung dropped on the field by grazing animals. The aim of this study was to determine the toxic threshold levels of three antibacterial agents (tiamulin, olanquindox and metronidazole) and one anthelmintic (ivermectin) to two species of soil dwelling organisms (springtails and enchytraeids), that are often found in bio-solids such as manure or dung. The antibacterial agents were not toxic to adults and effects on reproduction occurred generally above concentrations normally found in soil or dung. The threshold values for toxicity (10% reduced reproduction or EC10 values) were in the range of 61-111 mg kg(-1) dry soil for springtails and 83-722 mg kg(-1) dry soil for enchytraeids. Ivermectin was significantly more toxic with EC10 values of 0.26 mg kg(-1) dry soil for the springtails and 14 mg kg(-1) dry soil for the enchytraeids. A comparison of these results with rough estimates of likely and worse case environmental concentrations indicates a potential risk of ivermectin to non-target species such as springtails and enchytraeids, whereas direct toxic effect of antibacterial agents is very unlikely to occur at environmental realistic concentrations. However, indirect effects of antibacterial agents driven through changes in the food web cannot be abolished at this stage.

  12. Folliculitis et perifolliculitis capitis abscedens et suffodiens controlled with a combination therapy: systemic antibiosis (metronidazole plus clindamycin), dermatosurgical approach, and high-dose isotretinoin.

    PubMed

    Tchernev, Georgi

    2011-05-01

    Folliculitis et perifolliculitis capitis abscedens et suffodiens is a rare disease of unknown etiology. It is a suppurative process that involves the scalp, eventually resulting in extensive scarring and irreversible alopecia. The condition is also known as 'acne necrotica miliaris' or 'Proprionibacterium' folliculitis. Most often the disease affects men of African-American or African-Caribbean descent between 20 and 40 years of age. The clinical picture is determined by fluctuating painful fistule-forming conglomerates of abscesses in the region of the occipital scalp. The cause of scalp folliculitis is not well understood. It is generally considered to be an inflammatory reaction to components of the hair follicle, particularly the micro-organisms. These include: bacteria (especially Propionibacterium acnes, but in severe cases, also Staphylococcus aureus), Yeasts (Malassezia species) and mites (Demodex folliculorum). The initial histopathologic finding is an exclusively neutrophilic infiltration followed by a granulomatous infiltrate. The treatment of the disease is usually difficult and often disappointing. Successful treatment with isotretinoin 1 mg/kg body mass could be achieved only after regular systematic administration in the course of 3-4 months. Here we describe a patient with eruptive purulent form of the disease, which has been controlled with combination therapy: systemic antibiosis with metronidazole and clindamycin, dermatosurgical removal of single nodular formations, and isotretinoin 1 mg/kg body mass for 3-5 months.

  13. A rapid, high-throughput viability assay for Blastocystis spp. reveals metronidazole resistance and extensive subtype-dependent variations in drug susceptibilities.

    PubMed

    Mirza, Haris; Teo, Joshua D W; Upcroft, Jacqui; Tan, Kevin S W

    2011-02-01

    Blastocystis is an emerging protistan parasite of controversial pathogenesis. Although metronidazole (Mz) is standard therapy for Blastocystis infections, there have been accumulating reports of treatment failure, suggesting the existence of drug-resistant isolates. Furthermore, very little is known about Blastocystis susceptibility to standard antimicrobials. In the present study, we established resazurin and XTT viability microassays for Blastocystis spp. belonging to subtypes 4 and 7, both of which have been suggested to represent pathogenic zoonotic subtypes. The optimized resazurin assay was used to screen a total of 19 compounds against both subtypes. Interestingly, subtype 7 parasites were resistant to Mz, a 1-position-substituted 5-nitroimidazole (5-NI), while subtype 4 parasites were sensitive. Some cross-resistance was observed to tinidazole, another 1-position 5-NI. Conversely, subtype 4 parasites were resistant to emetine, while subtype 7 parasites were sensitive. Position 2 5-NIs were effective against both subtypes, as were ornidazole, nitazoxanide, furazolidone, mefloquine, quinicrine, quinine, cotrimoxazole (trimethoprim-sulfamethoxazole), and iodoacetamide. Both subtypes were resistant to chloroquine, doxycycline, paromomycin, ampicillin, and pyrimethamine. This is the first study to report extensive variations in drug sensitivities among two clinically important subtypes. Our study highlights the need to reevaluate established treatment regimens for Blastocystis infections and offers clear new treatment options for Mz treatment failures.

  14. Novel electrochemical sensing platform based on a molecularly imprinted polymer decorated 3D nanoporous nickel skeleton for ultrasensitive and selective determination of metronidazole.

    PubMed

    Li, Yingchun; Liu, Yuan; Yang, Yang; Yu, Feng; Liu, Jie; Song, Han; Liu, Jiang; Tang, Hui; Ye, Bang-Ce; Sun, Zhipeng

    2015-07-22

    A novel electrochemical sensor has been developed by using a composite element of three-dimensional (3D) nanoporous nickel (NPNi) and molecularly imprinted polymer (MIP). NPNi is introduced in order to enhance the electron-transport ability and surface area of the sensor, while the electrosynthesized MIP layer affords simultaneous identification and quantification of the target molecule by employing Fe(CN)6(3-/4-) as the probe to indicate the current intensity. The morphology of the hybrid film was observed by scanning electron microscopy, and the properties of the sensor were examined by cyclic voltammetry and electrochemical impedance spectroscopy. By using metronidazole (MNZ) as a model analyte, the sensor based on the MIP/NPNi hybrid exhibits great features such as a remarkably low detection limit of 2 × 10(-14) M (S/N = 3), superb selectivity in discriminating MNZ from its structural analogues, and good antiinterference ability toward several coexisting substances. Moreover, the proposed method also demonstrates excellent repeatability and stability, with relative standard deviations of less than 1.12% and 1.4%, respectively. Analysis of MNZ in pharmaceutical dosage form and fish tissue is successfully carried out without assistance of complicated pretreatment. The MIP/NPNi composite presented here with admirable merits makes it a promising candidate for developing electrochemical sensor devices and plays a role in widespread fields.

  15. Iron doped SnO2/Co3O4 nanocomposites synthesized by sol-gel and precipitation method for metronidazole antibiotic degradation.

    PubMed

    Agarwal, Shilpi; Tyagi, Inderjeet; Gupta, Vinod Kumar; Sohrabi, Maryam; Mohammadi, Sanaz; Golikand, Ahmad Nozad; Fakhri, Ali

    2017-01-01

    Sol-gel and precipitation reaction methods were used to synthesize Un-doped and Fe-doped SnO2/Co3O4 nanocomposites under UV light; the synthesized nanocomposites were applied for the photocatalytic degradation of metronidazole antibiotic. The developed photo catalyst was well characterized using energy dispersive X-ray spectrometer (EDX), X-ray diffraction (XRD), vibrating sample magnetometer (VSM), field emission scanning electron microscopy (FE-SEM), UV-Visible and photoluminescence (PL) spectroscopy. Effective parameters such as pH, photocatalyst dose and contact time was optimized and well investigated. From the obtained facts it is clear that the 98.3% of MTZ was degraded with in 15min, pH6 and 0.1g catalyst when the Fe molar ratio was 1:1 at %. As compared to results obtained from un-doped SnO2/Co3O4 nanocomposites Fe doped SnO2/Co3O4 nanocomposites possess greater photocatalytic efficiency.

  16. In Vitro Activity of Ceftolozane-Tazobactam against Anaerobic Organisms Identified during the ASPECT-cIAI Study

    PubMed Central

    Farrell, David J.; Palchak, Melissa; Steenbergen, Judith N.

    2015-01-01

    The in vitro activities of ceftolozane-tazobactam, meropenem, and metronidazole were determined against anaerobic organisms isolated from patients with complicated intraabdominal infections (cIAI) in global phase III studies. Ceftolozane-tazobactam activity was highly variable among different species of the Bacteroides fragilis group, with MIC90 values ranging from 2 to 64 μg/ml. More-potent in vitro activity was observed against selected Gram-positive anaerobic organisms; however, small numbers of isolates were available, and, therefore, the clinical significance of these results is unknown. Variable activity of ceftolozane-tazobactam against anaerobic organisms necessitates use in combination with metronidazole for the treatment of cIAI. PMID:26552971

  17. Hydrophobicity of imidazole derivatives correlates with improved activity against human methanogenic archaea.

    PubMed

    Khelaifia, Saber; Brunel, Jean Michel; Raoult, Didier; Drancourt, Michel

    2013-06-01

    Methanogenic archaea are involved in periodontitis in humans. They have also been implicated in digestive tract pathologies and obesity. These microorganisms are broadly resistant to antibiotics, except for metronidazole and ornidazole. In this study, eight imidazole derivatives were synthesised and their in vitro cytotoxicity and activity against six species of methanogenic archaea, including Methanobrevibacter smithii, Methanobrevibacter oralis, Methanosphaera stadtmanae, Methanobacterium beijingense, Methanosaeta concilii and Methanomassiliicoccus luminyensis, were tested. Whilst the effective half-maximum cytotoxic concentrations (EC50 values) of all compounds were ≤50 mg/L, minimum inhibitory concentrations (MICs) were 0.05-0.8 mg/L for most methanogenic archaea and 0.1-1mg/L for M. stadtmanae. These results indicated a >20-400 therapeutic index (EC50/MIC) for these compounds, which compared with metronidazole exhibited 1-log increased activity against methanogenic archaea cultured from the human microbiota. These compounds are therefore promising molecules for the treatment of methanogenic archaea-related infections.

  18. Activity of human beta-defensin 3 alone or combined with other antimicrobial agents against oral bacteria.

    PubMed

    Maisetta, Giuseppantonio; Batoni, Giovanna; Esin, Semih; Luperini, Filippo; Pardini, Manuela; Bottai, Daria; Florio, Walter; Giuca, Maria Rita; Gabriele, Mario; Campa, Mario

    2003-10-01

    The in vitro activities of human beta-defensin 3 (hBD-3) alone or combined with lysozyme, metronidazole, amoxicillin, and chlorhexidine were investigated with the oral bacteria Streptococcus mutans, Streptococcus sanguinis, Streptococcus sobrinus, Lactobacillus acidophilus, Actinobacillus actinomycetemcomitans, and Porphyromonas gingivalis. hBD-3 showed bactericidal activity against all of the bacterial species tested. The bactericidal effect was enhanced when the peptide was used in combination with the antimicrobial agents mentioned above.

  19. A RANDOMIZED TREATMENT TRIAL: SINGLE VERSUS 7 DAY DOSE OF METRONIDAZOLE FOR THE TREATMENT OF TRICHOMONAS VAGINALIS AMONG HIV-INFECTED WOMEN

    PubMed Central

    Kissinger, Patricia; Mena, Leandro; Levison, Judy; Clark, Rebecca A.; Gatski, Megan; Henderson, Harold; Schmidt, Norine; Rosenthal, Susan; Myers, Leann; Martin, David H.

    2010-01-01

    Objective To determine if the metronidazole (MTZ) 2 gm single dose (recommended) is as effective as the 7 day 500 mg BID dose (alternative) for treatment of Trichomonas vaginalis (TV) among HIV+ women. Methods Phase IV randomized clinical trial; HIV+ women with culture confirmed TV were randomized to treatment arm: MTZ 2 gm single dose or MTZ 500 mg BID 7 day dose. All women were given 2 gm MTZ doses to deliver to their sex partners. Women were re-cultured for TV at a test-of-cure (TOC) visit occurring 6-12 days after treatment completion. TV-negative women at TOC were again re-cultured at a 3 month visit. Repeat TV infection rates were compared between arms. Results 270 HIV+/TV+ women were enrolled (mean age = 40 years, ± 9.4; 92.2% African-American). Treatment arms were similar with respect to age, race, CD4 count, viral load, ART status, site, and loss-to-follow up. Women in the 7 day arm had: lower repeat TV infection rates at TOC [8.5% (11/130) versus 16.8% (21/125) (R.R. 0.50, 95% CI=0.25, 1.00; P<0.05)], and at 3 months [11.0% (8/73) versus 24.1% (19/79) (R.R. 0.46, 95% CI=0.21, 0.98; P=0.03)] compared to the single dose arm. Conclusions The 7 day MTZ dose was more effective than the single dose for the treatment of TV among HIV+ women. PMID:21423852

  20. Conjugation of metronidazole with dextran: a potential pharmaceutical strategy to control colonic distribution of the anti-amebic drug susceptible to metabolism by colonic microbes

    PubMed Central

    Kim, Wooseong; Yang, Yejin; Kim, Dohoon; Jeong, Seongkeun; Yoo, Jin-Wook; Yoon, Jeong-Hyun; Jung, Yunjin

    2017-01-01

    Metronidazole (MTDZ), the drug of choice for the treatment of protozoal infections such as luminal amebiasis, is highly susceptible to colonic metabolism, which may hinder its conversion from a colon-specific prodrug to an effective anti-amebic agent targeting the entire large intestine. Thus, in an attempt to control the colonic distribution of the drug, a polymeric colon-specific prodrug, MTDZ conjugated to dextran via a succinate linker (Dex-SA-MTDZ), was designed. Upon treatment with dextranase for 8 h, the degree of Dex-SA-MTDZ depolymerization (%) with a degree of substitution (mg of MTDZ bound in 100 mg of Dex-SA-MTDZ) of 7, 17, and 30 was 72, 38, and 8, respectively, while that of dextran was 85. Depolymerization of Dex-SA-MTDZ was found to be necessary for the release of MTDZ, because dextranase pretreatment ensures that de-esterification occurs between MTDZ and the dextran backbone. In parallel, Dex-SA-MTDZ with a degree of substitution of 17 was found not to release MTDZ upon incubation with the contents of the small intestine and stomach of rats, but it released MTDZ when incubated with rat cecal contents (including microbial dextranases). Moreover, Dex-SA-MTDZ exhibited prolonged release of MTDZ, which contrasts with drug release by small molecular colon-specific prodrugs, MTDZ sulfate and N-nicotinoyl-2-{2-(2-methyl-5-nitroimidazol-1-yl)ethyloxy}-d,l-glycine. These prodrugs were eliminated very rapidly, and no MTDZ was detected in the cecal contents. Consistent with these in vitro results, we found that oral gavage of Dex-SA-MTDZ delivered MTDZ (as MTDZ conjugated to [depolymerized] dextran) to the distal colon. However, upon oral gavage of the small molecular prodrugs, no prodrugs were detected in the distal colon. Collectively, these data suggest that dextran conjugation is a potential pharmaceutical strategy to control the colonic distribution of drugs susceptible to colonic microbial metabolism. PMID:28243064

  1. Intra-Subtype Variation in Enteroadhesion Accounts for Differences in Epithelial Barrier Disruption and Is Associated with Metronidazole Resistance in Blastocystis Subtype-7

    PubMed Central

    Tan, Kevin Shyong Wei

    2014-01-01

    Blastocystis is an extracellular, enteric pathogen that induces intestinal disorders in a range of hosts including humans. Recent studies have identified potential parasite virulence factors in and host responses to this parasite; however, little is known about Blastocystis-host attachment, which is crucial for colonization and virulence of luminal stages. By utilizing 7 different strains of the parasite belonging to two clinically relevant subtypes ST-4 and ST-7, we investigated Blastocystis-enterocyte adhesion and its association with parasite-induced epithelial barrier disruption. We also suggest that drug resistance in ST-7 strains might result in fitness cost that manifested as impairment of parasite adhesion and, consequently, virulence. ST-7 parasites were generally highly adhesive to Caco-2 cells and preferred binding to intercellular junctions. These strains also induced disruption of ZO-1 and occludin tight junction proteins as well as increased dextran-FITC flux across epithelial monolayers. Interestingly, their adhesion was correlated with metronidazole (Mz) susceptibility. Mz resistant (Mzr) strains were found to be less pathogenic, owing to compromised adhesion. Moreover, tolerance of nitrosative stress was also reduced in the Mzr strains. In conclusion, the findings indicate that Blastocystis attaches to intestinal epithelium and leads to epithelial barrier dysfunction and that drug resistance might entail a fitness cost in parasite virulence by limiting entero-adhesiveness. This is the first study of the cellular basis for strain-to-strain variation in parasite pathogenicity. Intra- and inter-subtype variability in cytopathogenicity provides a possible explanation for the diverse clinical outcomes of Blastocystis infections. PMID:24851944

  2. Anti-Helicobacter pylori activity of some newly synthesized derivatives of xanthone.

    PubMed

    Klesiewicz, Karolina; Karczewska, Elżbieta; Budak, Alicja; Marona, Henryk; Szkaradek, Natalia

    2016-11-01

    A series of 20 xanthone derivatives was synthesized and evaluated for anti-Helicobacter pylori (H. pylori) activity. Qualitative and quantitative in vitro tests using the Kirby-Bauer method (agar disc-diffusion method) were performed. The tested compounds were screened against clarithromycin- and/or metronidazole-resistant strains of H. pylori. As a reference, Gram-positive (Staphylococcus aureus) and Gram-negative (Escherichia coli) bacterial strains were examined. On the basis of microbiological assays, xanthones can be considered as potential anti-H. pylori agents. They displayed significant activity against the examined strains, which was higher against the bacteria resistant to metronidazole than clarithromycin. The lowest MIC values ranging up to 20 mg l(-1) were observed for the following compounds: 3, 4, 8, 9, 12, 19 (against the metronidazole-resistant strains) and the compound 10 (against the clarithromycin-resistant strain). These preliminary results for screening of xanthone derivatives form a part of an ongoing study of the structure-activity relationships of a large group of compounds. Microbiological assays will be conducted afterwards to determine the mechanism of xanthones' action against H. pylori.

  3. Nitroheterocyclic drugs with broad spectrum activity.

    PubMed

    Raether, W; Hänel, H

    2003-06-01

    The group of biologically active nitroheterocyclic compounds includes various 5- and 2-nitroimidazoles and 5-nitrofurans, which can be used as therapeutic agents against a variety of protozoan and bacterial (anaerobic) infections of humans and animals. The current status in the the treatment of giardiasis, trichomoniasis, balantidiasis, histomoniasis, and amebiasis (including infections due to opportunistic amebas) is presented. The most relevant drugs (benznidazole, furazolidone, metronidazole, misonidazole, nifurtimox, nimorazole, nitazoxanide, ornidazole, secnidazole, and tinidazole) are characterized with regard to their chemical, chemotherapeutic, toxicological, pharmacokinetic, and pharmacological properties, including the mechanism of action and resistance in certain parasitic protozoa.

  4. Detection of Porphyromonas gingivalis and Aggregatibacter actinomycetemcomitans after Systemic Administration of Amoxicillin Plus Metronidazole as an Adjunct to Non-surgical Periodontal Therapy: A Systematic Review and Meta-Analysis

    PubMed Central

    Dakic, Aleksandar; Boillot, Adrien; Colliot, Cyrille; Carra, Maria-Clotilde; Czernichow, Sébastien; Bouchard, Philippe

    2016-01-01

    Objective: To evaluate the variations in the detection of Porphyromonas gingivalis and/or Aggregatibacter actinomycetemcomitans before and after systemic administration of amoxicillin plus metronidazole in association with non-surgical periodontal therapy (NSPT). Background: The adjunctive use of antibiotics has been advocated to improve the clinical outcomes of NSPT. However, no systematic review has investigated the microbiological benefit of this combination. Materials and Methods: An electronic search was conducted up to December 2015. Randomized clinical trials comparing the number of patients testing positive for P. gingivalis and/or A. actinomycetemcomitans before and after NSPT with (test group) or without (control group) amoxicillin plus metronidazole were included. The difference between groups in the variation of positive patients was calculated using the inverse variance method with a random effects model. Results: The frequency of patients positive for A. actinomycetemcomitans was decreased by 30% (p = 0.002) and by 25% (p = 0.01) in the test group compared to the control group at 3- and 6-month follow-up, respectively. Similar findings were observed when considering the frequency of patients positive for Porphyromonas gingivalis, with a reduction by 28% (p < 0.0001), 32% (p < 0.0001), and 34% (p = 0.03) in the test group compared to the control group at 3-, 6-, and 12-month follow-up, respectively. Conclusion: The systemic administration of amoxicillin plus metronidazole as an adjunct to NSPT significantly decreased the number of patients positive for P. gingivalis and A. actinomycetemcomitans compared with periodontal therapy alone or with a placebo. PMID:27594851

  5. In vitro dissolution of generic immediate-release solid oral dosage forms containing BCS class I drugs: comparative assessment of metronidazole, zidovudine, and amoxicillin versus relevant comparator pharmaceutical products in South Africa and India.

    PubMed

    Reddy, Nallagundla H S; Patnala, Srinivas; Löbenberg, Raimar; Kanfer, Isadore

    2014-10-01

    Biowaivers are recommended for immediate-release solid oral dosage forms using dissolution testing as a surrogate for in vivo bioequivalence studies. Several guidance are currently available (the World Health Organization (WHO), the US FDA, and the EMEA) where the conditions are described. In this study, definitions, criteria, and methodologies according to the WHO have been applied. The dissolution performances of immediate-release metronidazole, zidovudine, and amoxicillin products purchased in South African and Indian markets were compared to the relevant comparator pharmaceutical product (CPP)/reference product. The dissolution performances were studied using US Pharmacopeia (USP) apparatus 2 (paddle) set at 75 rpm in each of three dissolution media (pH1.2, 4.5, and 6.8). Concentrations of metronidazole, zidovudine, and amoxicillin in each dissolution media were determined by HPLC. Of the 11 metronidazole products tested, only 8 could be considered as very rapidly dissolving products as defined by the WHO, whereas 2 of those products could be considered as rapidly dissolving products but did not comply with the f 2 acceptance criteria in pH 6.8. All 11 zidovudine products were very rapidly dissolving, whereas in the case of the 14 amoxicillin products tested, none of those products met any of the WHO criteria. This study indicates that not all generic products containing the same biopharmaceutics classification system (BCS) I drug and in similar strength and dosage form are necessarily in vitro equivalent. Hence, there is a need for ongoing market surveillance to determine whether marketed generic products containing BCS I drugs meet the release requirements to confirm their in vitro bioequivalence to the respective reference product.

  6. In vivo antigiardial activity of three flavonoids isolated of some medicinal plants used in Mexican traditional medicine for the treatment of diarrhea.

    PubMed

    Barbosa, Elizabeth; Calzada, Fernando; Campos, Rafael

    2007-02-12

    Mexican traditional medicine uses a great variety of plants in the treatment of gastrointestinal disorders such as diarrhea. In order to understand the properties of some of their chemical constituents, three flavonoids (kaempferol, tiliroside and (-)-epicatechin) isolated from Geranium mexicanum, Cuphea pinetorum, Helianthemum glomeratum, and Rubus coriifolius, were assayed to demonstrate their in vivo antiprotozoal activity; using an experimental infection of Giardia lamblia in suckling female CD-1 mice. Compounds tested showed antigiardial activity with values of ED(50) (micromol/kg) 0.072 for (-)-epicatechin, 2.057 for kaempferol and 1.429 for tiliroside. The most active flavonoid was the (-)-epicatechin, its activity was higher than metronidazole and emetine, drugs used as positive controls. In the case of kaempferol and tiliroside their potency was close to that of the metronidazole, but far less than emetine.

  7. Direct activation of the Mauthner cell by electric field pulses drives ultrarapid escape responses

    PubMed Central

    Tabor, Kathryn M.; Bergeron, Sadie A.; Horstick, Eric J.; Jordan, Diana C.; Aho, Vilma; Porkka-Heiskanen, Tarja; Haspel, Gal

    2014-01-01

    Rapid escape swims in fish are initiated by the Mauthner cells, giant reticulospinal neurons with unique specializations for swift responses. The Mauthner cells directly activate motoneurons and facilitate predator detection by integrating acoustic, mechanosensory, and visual stimuli. In addition, larval fish show well-coordinated escape responses when exposed to electric field pulses (EFPs). Sensitization of the Mauthner cell by genetic overexpression of the voltage-gated sodium channel SCN5 increased EFP responsiveness, whereas Mauthner ablation with an engineered variant of nitroreductase with increased activity (epNTR) eliminated the response. The reaction time to EFPs is extremely short, with many responses initiated within 2 ms of the EFP. Large neurons, such as Mauthner cells, show heightened sensitivity to extracellular voltage gradients. We therefore tested whether the rapid response to EFPs was due to direct activation of the Mauthner cells, bypassing delays imposed by stimulus detection and transmission by sensory cells. Consistent with this, calcium imaging indicated that EFPs robustly activated the Mauthner cell but only rarely fired other reticulospinal neurons. Further supporting this idea, pharmacological blockade of synaptic transmission in zebrafish did not affect Mauthner cell activity in response to EFPs. Moreover, Mauthner cells transgenically expressing a tetrodotoxin (TTX)-resistant voltage-gated sodium channel retained responses to EFPs despite TTX suppression of action potentials in the rest of the brain. We propose that EFPs directly activate Mauthner cells because of their large size, thereby driving ultrarapid escape responses in fish. PMID:24848468

  8. Effects of age, species difference, antibiotics and toxicants on intestinal enzyme activity and genotoxicity

    SciTech Connect

    Chadwick, R.W.; George, S.E.; Kohan, M.J.; Allison, J.C. . Health Effects Research Lab.); Chang, J.; Long, J.E.; Duffy, M.C. ); Dekker, J.P.; Forehand, L.R. )

    1993-08-01

    Altered intestinal enzyme activity significantly affects the biotransformation and toxicity of many xenobiotics. This article summarizes research, supported by the US Air Force Bioenvironmental Hazards Research Program, that employs a novel gas-liquid chromatographic assay to investigate the effects of age, species difference, antibiotics, and environmental chemicals on enzyme activity in various regions of the intestinal tract. Significant research findings include the following: (a) age-dependent alterations in enzyme activity in the gastrointestinal (GI) tract of the developing animal that suggest a changing susceptibility to toxicants during this period; (b) discovery of previously unreported mucosal enzymes in the small intestine that are present in germ-free rats and are not susceptible to antibiotics; (c) markedly greater intestinal nitroreductase activity and significantly higher bioactivation of the procarcinogen 2,6-dinitrotoluene (DNT) in CD-1 mice than in Fischer 344 rats; (d) significantly altered intestinal enzyme activity in rats pretreated with lindane, pentachlorophenol, 2,4,5-trichlorophenoxyacetic acid (2,4,5-T), or Aroclor 1254; (e) potentiated DNT genotoxicity by Aroclor 1254 and pentachlorophenol pretreatment; and (f) a transient antagonism of DNT genotoxicity by 2,4,5-T pretreatment. Enzyme activity in the small intestine may have greater toxicological importance than previously thought in the biotransformation of environmental chemicals and as an indicator of change in the microbial flora.

  9. Eicosapentaenoic Acid Modulates Trichomonas vaginalis Activity.

    PubMed

    Korosh, Travis; Jordan, Kelsey D; Wu, Ja-Shin; Yarlett, Nigel; Upmacis, Rita K

    2016-01-01

    Trichomonas vaginalis is a sexually transmitted parasite and, while it is often asymptomatic in males, the parasite is associated with disease in both sexes. Metronidazole is an effective treatment for trichomoniasis, but resistant strains have evolved and, thus, it has become necessary to investigate other possible therapies. In this study, we examined the effects of native and oxidized forms of the sodium salts of eicosapentaenoic, docosahexaenoic, and arachidonic acids on T. vaginalis activity. Eicosapentaenoic acid was the most toxic with 190 and 380 μM causing approximately 90% cell death in Casu2 and ATCC 50142 strains, respectively. In contrast, oxidized eicosapentaenoic acid was the least toxic, requiring > 3 mM to inhibit activity, while low levels (10 μM) were associated with increased parasite density. Mass spectrometric analysis of oxidized eicosapentaenoic acid revealed C20 products containing one to six additional oxygen atoms and various degrees of bond saturation. These results indicate that eicosapentaenoic acid has different effects on T. vaginalis survival, depending on whether it is present in the native or oxidized form. A better understanding of lipid metabolism in T. vaginalis may facilitate the design of synthetic fatty acids that are effective for the treatment of metronidazole-resistant T. vaginalis.

  10. The Impact of Handling and Storage of Human Fecal Material on Bacterial Activity.

    PubMed

    Karatza, Eleni; Vertzoni, Maria; Muenster, Uwe; Reppas, Christos

    2016-11-01

    Fecal material prepared from human stools is frequently used for the assessment of bacterial degradation of active pharmaceutical ingredients as relevant data are useful for evaluating the potential for colonic drug delivery. The impact of handling and storage of human fecal material on bacterial activity was assessed by evaluating the degradation characteristics of metronidazole and olsalazine. Multiple freeze (-70°C)-thaw cycles should be avoided. Incubation of frozen material for about 2 h in the anaerobic workstation ensures regeneration of the highest possible bacterial activity. Material could be stored at -70°C for at least 12 months.

  11. A Phase 3, Multicenter, Randomized, Double-Blind, Vehicle-Controlled Study Evaluating the Safety and Efficacy of Metronidazole Vaginal Gel 1.3% in the Treatment of Bacterial Vaginosis

    PubMed Central

    Schwebke, Jane R.; Marrazzo, Jeanne; Beelen, Andrew P.; Sobel, Jack D.

    2015-01-01

    Background Bacterial vaginosis (BV), a prevalent infection in women of reproductive age, is associated with increased risk of upper genital tract and sexually transmitted infections, and complications in pregnancy. Currently approved treatments include metronidazole, which requires once or twice daily intravaginal administration for 5 days or twice daily oral administration for 7 days. This phase 3 study determined the safety and efficacy of single-dose metronidazole vaginal gel (MVG) 1.3%. Methods In this double-blind, vehicle-controlled study, 651 women with clinical diagnosis of BV were randomized 1:1 to receive MVG 1.3% or vehicle vaginal gel. Primary efficacy measure was clinical cure (normal discharge, negative “whiff test,” and <20% clue cells) at day 21. Secondary measures included therapeutic cure (both clinical and bacteriological; day 21) and bacteriologic cure (Nugent score <4), clinical cure, and time to resolution of symptoms (day 7). Results A total of 487 participants were included in the primary analysis. Clinical and therapeutic cure rates (day 21) were higher in participants treated with MVG 1.3% compared with vehicle gel (37.2% vs. 26.6% [P = 0.010] and 16.8% vs. 7.2% [P = 0.001], respectively). Clinical and bacteriologic cure rates (day 7) were also higher in the MVG 1.3% group (46.0% vs. 20.0% [P < 0.001] and 32.7% vs. 6.3% [P < 0.001], respectively). The median time to resolution of symptoms was shorter in the MVG 1.3% (day 6) than vehicle group (not reached). No serious adverse events were reported, and incidence was similar across treatment groups. Conclusions Single-dose MVG 1.3% was safe and superior to vehicle gel in producing cure among women with BV. PMID:26222750

  12. Activity.

    ERIC Educational Resources Information Center

    Clearing: Nature and Learning in the Pacific Northwest, 1984

    1984-01-01

    Presents three activities: (1) investigating succession in a schoolground; (2) investigating oak galls; and (3) making sun prints (photographs made without camera or darkroom). Each activity includes a list of materials needed and procedures used. (JN)

  13. Reductive transformation of parathion and methyl parathion by Bacillus sp.

    PubMed

    Yang, Chao; Dong, Ming; Yuan, Yulan; Huang, Yao; Guo, Xinmin; Qiao, Chuanling

    2007-03-01

    Based on the results of phenotypic features, phylogenetic similarity of 16S rRNA gene sequences and BIOLOG test, a soil bacterium was identified as Bacillus sp. DM-1. Using either growing cells or a cell-free extract, it transformed parathion and methyl parathion to amino derivatives by reducing the nitro group. Pesticide transformation by a cell-free extract was specifically inhibited by three nitroreductase inhibitors, indicating the presence of nitroreductase activity. The nitroreductase activity was NAD(P)H-dependent, O(2)-insensitive, and exhibited the substrate specificity for parathion and methyl parathion. Reductive transformation significantly decreased the toxicity of pesticides.

  14. Activities.

    ERIC Educational Resources Information Center

    Bippert, Judy

    1993-01-01

    Presents activities designed to give students an opportunity to solve concrete problems involving spatial relationships and logical thinking utilizing hands-on manipulatives. Provides teacher instructions and four reproducible worksheets. (MDH)

  15. Enhancement of the adsorption capacity of the light-weight expanded clay aggregate surface for the metronidazole antibiotic by coating with MgO nanoparticles: Studies on the kinetic, isotherm, and effects of environmental parameters.

    PubMed

    Kalhori, Ebrahim Mohammadi; Al-Musawi, Tariq J; Ghahramani, Esmaeil; Kazemian, Hossein; Zarrabi, Mansur

    2017-02-09

    The synthesized MgO nanoparticles were used to coat the light-weight expanded clay aggregates (LECA) and as a metronidazole (MNZ) adsorbent. X-ray diffraction (XRD), scanning electron microscopy (SEM), transmission electron microscopy (TEM), and Fourier-transformed infrared (FTIR) techniques were employed to study the surface morphology and characteristics of the adsorbents. MgO/LECA clearly revealed the advantages of the nanocomposite particles, showing high specific surface area (76.12 m(2)/g), significant adsorption sites and functional groups. Between pH 5 and 9, the MNZ sorption was not significantly affected. Kinetic studies revealed that the MNZ adsorption closely followed the Avrami model, with no dominant process controlling the sorption rate. The study of the effects of foreign ions revealed that the addition of carbonate raised the MNZ removal efficiency of LECA by 8% and the total removal of MNZ by MgO/LECA. Furthermore, nitrate and hardness only marginally influenced the MNZ removal efficiency and their effects can be ranked in the order of carbonate>nitrate>hardness. The isotherm adsorption of MNZ was best fitted with the Langmuir model enlighten the monolayer MNZ adsorption on the homogeneous LECA and MgO/LECA surfaces. The maximum adsorption capacity under optimum conditions was enhanced from 56.31 to 84.55 mg/g for LECA and MgO/LECA, respectively. These findings demonstrated that the MgO/LECA nanocomposite showed potential as an efficient adsorbent for MNZ removal.

  16. Nitroimidazoles adsorption on activated carbon cloth from aqueous solution.

    PubMed

    Ocampo-Pérez, R; Orellana-Garcia, F; Sánchez-Polo, M; Rivera-Utrilla, J; Velo-Gala, I; López-Ramón, M V; Alvarez-Merino, M A

    2013-07-01

    The objective of this study was to analyze the equilibrium and adsorption kinetics of nitroimidazoles on activated carbon cloth (ACC), determining the main interactions responsible for the adsorption process and the diffusion mechanism of these compounds on this material. The influence of the different operational variables, such as ionic strength, pH, temperature, and type of water (ultrapure, surface, and waste), was also studied. The results obtained show that the ACC has a high capacity to adsorb nitroimidazoles in aqueous solution. Electrostatic interactions play an important role at pH<3, which favors the repulsive forces between dimetridazole or metronidazole and the ACC surface. The formation of hydrogen bonds and dispersive interactions play the predominant role at higher pH values. Modifications of the ACC with NH3, K2S2O8, and O3 demonstrated that its surface chemistry plays a predominant role in nitroimidazole adsorption on this material. The adsorption capacity of ACC is considerably high in surface waters and reduced in urban wastewater, due to the levels of alkalinity and dissolved organic matter present in the different types of water. Finally, the results of applying kinetic models revealed that the global adsorption rate of dimetridazole and metronidazole is controlled by intraparticle diffusion.

  17. Activities.

    ERIC Educational Resources Information Center

    Kincaid, Charlene; And Others

    1993-01-01

    Presents an activity in which students collect and organize data from a real-world simulation of the scientific concept of half life. Students collect data using a marble sifter, analyze the data using a graphing calculator, and determine an appropriate mathematical model. Includes reproducible worksheets. (MDH)

  18. Bacteriostatic and bactericidal activities of 24 antimicrobial agents against Campylobacter fetus subsp. jejuni.

    PubMed

    Vanhoof, R; Gordts, B; Dierickx, R; Coignau, H; Butzler, J P

    1980-07-01

    The bacteriostatic and bactericidal activities of 24 antimicrobial agents were tested with the Dynatech MIC 2000 system against 86 strains of Campylobacter fetus subsp. jejuni from human sources. The penicillins (penicillin G, ampicillin, amoxycillin, carbenicillin) had poor activity. Ampicillin and amoxycillin were equally active. Cefotaxime revealed a rather good activity. Erythromycin, gentamicin, tobramycin, amikacin, and furazolidone were the most active compounds. Two strains (2.3%) were resistant to erythromycin. One strain (1.2%) was completely resistant to tobramycin. The tetracyclines (tetracyline, doxycycline, minocycline) were generally effective, but 8% of the strains were totally resistant to them. Minocycline was the most active. Chloramphenicol, thiamphenicol, and clindamycin had good activity. The bacteriostatic and bactericidal distributions for colistin, nalidixic acid, and metronidazole were broad.

  19. In Vitro Activities of MCB3681 and Eight Comparators against Clostridium difficile Isolates with Known Ribotypes and Diverse Geographical Spread

    PubMed Central

    Pilling, Sally; Vernon, Jonathan; Wilcox, Mark H.

    2016-01-01

    ABSTRACT Treatments for Clostridium difficile infection remain limited, despite the introduction of fidaxomicin, and development of new agents is necessary. We determined the in vitro susceptibilities of 199 prevalent or emerging Clostridium difficile PCR ribotypes to MCB3681, a novel investigational quinolonyl-oxazolidinone, and 8 comparators (metronidazole, vancomycin, fidaxomicin, moxifloxacin, ciprofloxacin, clindamycin, tigecycline, and linezolid). MCB3681 showed good activity against C. difficile with no evidence of MCB3681 resistance in isolates showing either moxifloxacin or linezolid resistance or both moxifloxacin and linezolid resistance. PMID:27993853

  20. Drug resistance in Giardia duodenalis.

    PubMed

    Ansell, Brendan R E; McConville, Malcolm J; Ma'ayeh, Showgy Y; Dagley, Michael J; Gasser, Robin B; Svärd, Staffan G; Jex, Aaron R

    2015-11-01

    Giardia duodenalis is a microaerophilic parasite of the human gastrointestinal tract and a major contributor to diarrheal and post-infectious chronic gastrointestinal disease world-wide. Treatment of G. duodenalis infection currently relies on a small number of drug classes. Nitroheterocyclics, in particular metronidazole, have represented the front line treatment for the last 40 years. Nitroheterocyclic-resistant G. duodenalis have been isolated from patients and created in vitro, prompting considerable research into the biomolecular mechanisms of resistance. These compounds are redox-active and are believed to damage proteins and DNA after being activated by oxidoreductase enzymes in metabolically active cells. In this review, we explore the molecular phenotypes of nitroheterocyclic-resistant G. duodenalis described to date in the context of the protist's unusual glycolytic and antioxidant systems. We propose that resistance mechanisms are likely to extend well beyond currently described resistance-associated enzymes (i.e., pyruvate ferredoxin oxidoreductases and nitroreductases), to include NAD(P)H- and flavin-generating pathways, and possibly redox-sensitive epigenetic regulation. Mechanisms that allow G. duodenalis to tolerate oxidative stress may lead to resistance against both oxygen and nitroheterocyclics, with implications for clinical control. The present review highlights the potential for systems biology tools and advanced bioinformatics to further investigate the multifaceted mechanisms of nitroheterocyclic resistance in this important pathogen.

  1. Antibacterial activity of Tabebuia impetiginosa Martius ex DC (Taheebo) against Helicobacter pylori.

    PubMed

    Park, Byeoung-Soo; Lee, Hyun-Kyung; Lee, Sung-Eun; Piao, Xiang-Lan; Takeoka, Gary R; Wong, Rosalind Y; Ahn, Young-Joon; Kim, Jeong-Han

    2006-04-21

    The growth-inhibiting activity of Tabebuia impetiginosa Martius ex DC dried inner bark-derived constituents against Helicobacter pylori ATCC 43504 was examined using paper disc diffusion and minimum inhibitory concentration (MIC) bioassays. The activity of the isolated compounds was compared to that of the commercially available anti-Helicobacter pylori agents, amoxicillin, metronidazole, and tetracycline. The biologically active components of Tabebuia impetiginosa dried inner bark (taheebo) were characterized by spectroscopic analysis as 2-(hydroxymethyl)anthraquinone, anthraquinone-2-carboxylic acid, and 2-hydroxy-3-(3-methyl-2-butenyl)-1,4-naphthoquinone (lapachol). With the paper disc diffusion assay 2-(hydroxymethyl)anthraquinone exhibited strong activity against Helicobacter pylori ATCC 43504 at 0.01 mg/disc. Anthraquinone-2-carboxylic acid, lapachol and metronidazole were less effective, exhibiting moderate anti-Helicobacter pylori activity at 0.1 mg/disc. Amoxicillin and tetracycline were the most potent compounds tested, displaying very strong activity at 0.005 mg/disc. 2-(Hydroxymethyl)anthraquinone exhibited moderate activity at this dose. Tetracycline still had strong activity at 0.001 mg/disc while amoxicillin had little activity at this dose. In the MIC bioassay, 2-(hydroxymethyl)anthraquinone (2 microg/mL), anthraquinone-2-carboxylic acid (8 microg/mL), and lapachol (4 microg/mL) were more active than metronidazole (32 microg/mL) but less effective than amoxicillin (0.063 microg/mL) and tetracycline (0.5 microg/mL). The anti-Helicobacter pylori activity of seven 1,4-naphthoquinone derivatives (structurally related to lapachol), 1,4-naphthoquinone, 5,8-dihydroxy-1,4-naphthoquinone (naphthazarin), 2-methyl-1,4-naphthoquinone (menadione), 2-hydroxy-1,4-naphthoquinone (lawsone), 5-hydroxy-2-methyl-1,4-naphthoquinone (plumbagin), 5-hydroxy-1,4-naphthoquinone (juglone), and 2,3-dichloro-1,4-naphthoquinone (dichlone) was also evaluated using the paper disc

  2. Phthalocyanines functionalized with 2-methyl-5-nitro-1H-imidazolylethoxy and 1,4,7-trioxanonyl moieties and the effect of metronidazole substitution on photocytotoxicity.

    PubMed

    Wierzchowski, Marcin; Sobotta, Lukasz; Skupin-Mrugalska, Paulina; Kruk, Justyna; Jusiak, Weronika; Yee, Michael; Konopka, Krystyna; Düzgüneş, Nejat; Tykarska, Ewa; Gdaniec, Maria; Mielcarek, Jadwiga; Goslinski, Tomasz

    2013-10-01

    Four novel magnesium(II) and zinc(II) phthalocyanines bearing 1,4,7-trioxanonyl, polyether and/or (2-methyl-5-nitro-1H-imidazol-1-yl)ethoxy, heterocyclic substituents at their non-peripheral positions were synthesized and assessed in terms of physicochemical and biological properties. Magnesium phthalocyanine derivatives bearing polyether substituents (Pc-1), a mixed system of polyether and heterocyclic substituents (Pc-3), and four heterocyclic substituents (Pc-4), respectively, were synthesized following the Linstead macrocyclization reaction procedure. Zinc phthalocyanine (Pc-2) bearing polyether substituents at non-peripheral positions was synthesized following the procedure in n-pentanol with the zinc acetate, and DBU. Novel phthalocyanines were purified by flash column chromatography and characterized using NMR, MS, UV-Vis and HPLC. Moreover, two precursors in macrocyclization reaction phthalonitriles were characterized using X-ray. Photophysical properties of the novel macrocycles were evaluated, including UV-Vis spectra analysis and aggregation study. All macrocycles subjected to singlet oxygen generation and the oxidation rate constant measurements exhibited lower quantum yields of singlet oxygen generation in DMSO than in DMF. In addition, the Pc-2 molecule was found to be the most efficient singlet oxygen generator from the group of macrocycles studied. The photocytotoxicity evaluated on the human oral squamous cell carcinoma cell line, HSC-3, for Pc-3 was significantly higher than that for Pc-1, Pc-2, and Pc-4. Interestingly, Pc-3 was found to be the most active macrocycle in vitro although its ability to generate singlet oxygen was significantly lower than those of Pc-1 and Pc-2. However, attempts to encapsulate phthalocyanines Pc-1-Pc-3 in liposomal membranes were unsuccessful. The phthalocyanine-nitroimidazole conjugate, Pc-4 was encapsulated in phosphatidylglycerol:phosphatidylcholine unilamellar liposomes and subjected to photocytotoxicity study.

  3. Comparison of Microbiological, Histological, and Immunomodulatory Parameters in Response to Treatment with Either Combination Therapy with Prednisone and Metronidazole or Probiotic VSL#3 Strains in Dogs with Idiopathic Inflammatory Bowel Disease

    PubMed Central

    Rossi, Giacomo; Pengo, Graziano; Caldin, Marco; Palumbo Piccionello, Angela; Steiner, Jörg M.; Cohen, Noah D.; Jergens, Albert E.; Suchodolski, Jan S.

    2014-01-01

    Background Idiopathic inflammatory bowel disease (IBD) is a common chronic enteropathy in dogs. There are no published studies regarding the use of probiotics in the treatment of canine IBD. The objectives were to compare responses to treatment with either combination therapy (prednisone and metronidazole) or probiotic strains (VSL#3) in dogs with IBD. Methodology and Principal Findings Twenty pet dogs with a diagnosis of IBD, ten healthy pet dogs, and archived control intestinal tissues from three euthanized dogs were used in this open label study. Dogs with IBD were randomized to receive either probiotic (D-VSL#3, n = 10) or combination drug therapy (D-CT, n = 10). Dogs were monitored for 60 days (during treatment) and re-evaluated 30 days after completing treatment. The CIBDAI (P<0.001), duodenal histology scores (P<0.001), and CD3+ cells decreased post-treatment in both treatment groups. FoxP3+ cells (p<0.002) increased in the D-VSL#3 group after treatment but not in the D-CT group. TGF-β+ cells increased in both groups after treatment (P = 0.0043) with the magnitude of this increase being significantly greater for dogs in the D-VSL#3 group compared to the D-CT group. Changes in apical junction complex molecules occludin and claudin-2 differed depending on treatment. Faecalibacterium and Turicibacter were significantly decreased in dogs with IBD at T0, with a significant increase in Faecalibacterium abundance observed in the animals treated with VSL#3 strains. Conclusions A protective effect of VSL#3 strains was observed in dogs with IBD, with a significant decrease in clinical and histological scores and a decrease in CD3+ T-cell infiltration. Protection was associated with an enhancement of regulatory T-cell markers (FoxP3+ and TGF-β+), specifically observed in the probiotic-treated group and not in animals receiving combination therapy. A normalization of dysbiosis after long-term therapy was observed in the probiotic group. Larger scale

  4. Marked antigiardial activity of Yucca baccata extracts: a potential natural alternative for treating protozoan infections.

    PubMed

    Quihui-Cota, Luis; León-Trujillo, Rocio; Astiazarán-García, Humberto; Esparza-Romero, Julián; del Refugio Robles, María; Robles-Zepeda, Ramón E; Canett, Rafael; Sánchez-Escalante, Jesús

    2014-01-01

    Human giardiosis is a public health problem in Mexico, where the national prevalence was estimated to be up to 68%. Misuse of antiprotozoal drugs may result in low effectiveness and undesirable side effects. Research on natural products is a good strategy for discovering more effective antiparasitic compounds. This study evaluated the antigiardial activity of extracts of Yucca baccata, which is native to northwestern Mexico. Forty-two gerbils (females) were weighed and orally inoculated with 5 × 10(6) Giardia trophozoites. Two gerbils were selected at random to confirm infection. Forty living gerbils were randomly allocated into 5 treatment groups (8 per group). Gerbils were randomly assigned to be treated with 24.4 mg/mL, 12.2 mg/mL, and 6.1 mg/mL of extracts, metronidazole (2 mg/mL) or PBS, which were intragastrically administered once per day for 3 days. Nine gerbils died during the study course. On day 10 postinfection, gerbils were euthanized and trophozoites were quantified. Yucca extracts reduced, albeit not significantly, the trophozoite counts in the duodenum segment. Only the high-extract concentration significantly reduced the trophozoite counts in the proximal segment and it was similar to that of metronidazole. Extracts of Y. baccata may represent an effective and natural therapeutic alternative for human giardiosis.

  5. Marked Antigiardial Activity of Yucca baccata Extracts: A Potential Natural Alternative for Treating Protozoan Infections

    PubMed Central

    Quihui-Cota, Luis; León-Trujillo, Rocio; Astiazarán-García, Humberto; Esparza-Romero, Julián; Robles, María del Refugio; Robles-Zepeda, Ramón E.; Canett, Rafael; Sánchez-Escalante, Jesús

    2014-01-01

    Human Giardiosis is a public health problem in Mexico, where the national prevalence was estimated to be up to 68%. Misuse of antiprotozoal drugs may result in low effectiveness and undesirable side effects. Research on natural products is a good strategy for discovering more effective antiparasitic compounds. This study evaluated the antigiardial activity of extracts of Yucca baccata, which is native to northwestern Mexico. Forty-two gerbils (females) were weighed and orally inoculated with 5 × 106 Giardia trophozoites. Two gerbils were selected at random to confirm infection. Forty living gerbils were randomly allocated into 5 treatment groups (8 per group). Gerbils were randomly assigned to be treated with 24.4 mg/mL, 12.2 mg/mL, and 6.1 mg/mL of extracts, metronidazole (2 mg/mL) or PBS, which were intragastrically administered once per day for 3 days. Nine gerbils died during the study course. On day 10 postinfection, gerbils were euthanized and trophozoites were quantified. Yucca extracts reduced, albeit not significantly, the trophozoite counts in the duodenum segment. Only the high-extract concentration significantly reduced the trophozoite counts in the proximal segment and it was similar to that of metronidazole. Extracts of Y. baccata may represent an effective and natural therapeutic alternative for human giardiosis. PMID:25250335

  6. Secnidazole. A review of its antimicrobial activity, pharmacokinetic properties and therapeutic use in the management of protozoal infections and bacterial vaginosis.

    PubMed

    Gillis, J C; Wiseman, L R

    1996-04-01

    Secnidazole is structurally related to the commonly used 5-nitroimidazoles metronidazole and tinidazole. These drugs share a common spectrum of activity against anaerobic micro-organisms and they appear particularly effective in the treatment of amoebiasis, giardiasis, trichomoniasis and bacterial vaginosis. Secnidazole is rapidly and completely absorbed after oral administration and has a longer terminal elimination half-life (approximately 17 to 29 hours) than commonly used drugs in this class. in patients with intestinal amoebiasis or giardiasis, clinical or parasistological cure rates of 80 to 100% are achieved after treatment with a single dose of secnidazole 2g (30 mg/kg in children), similar to the response rates achieved with multiple dosage regimens of metronidazole or tinidazole. Patients with hepatic amoebiasis appears to respond well to 5- to 7-day therapy with secnidazole, but the efficacy of this drug regimen requires further evaluation in larger numbers of patients. After administration of a single dose of secnidazole, parasitological eradication was achieved in approximately 92 to 100% of patients with urogenital trichomoniasis. Patients with bacteria vaginosis respond at least as well to a single dose of secnidazole as to single-dose tinidazole, or single- or 7-day treatment with metronidazole; clinical improvement and/or microbiological evidence of cure was attained in approximately 59 to 96% of patients. In the clinical trials reviewed, secnidazole was well tolerated; most adverse events were gastrointestinal in nature and did not require treatment intervention or withdrawal from therapy. In summary, available evidence suggests that secnidazole is as efficacious as other 5-nitroimidazole drugs in the treatment of protozoal infections and bacterial vaginosis. The convenience and ease of administration associated with single-dose therapy, combined with a good tolerability profile, make secnidazole a suitable option to other single-dose treatments

  7. Palladium(II) complexes of OS donor N-(di(butyl/phenyl)carbamothioyl)benzamide and their antiamoebic activity.

    PubMed

    Maurya, Mannar R; Uprety, Bhawna; Avecilla, Fernando; Tariq, Saba; Azam, Amir

    2015-06-15

    Two promising palladium(II) compounds of general formula, cis-[Pd(L-O,S)2] [where HL-O,S = N-(di(butyl/phenyl)carbamothioyl)benzamide] as metal based antiamoebic drug candidates, have been synthesized. Both complexes are characterized in the solid state by FT-IR spectroscopy, TGA and single crystal X-ray study, as well as in solution by other spectroscopic techniques such as (1)H and (13)C NMR, and UV-visible. All these studies confirm the coordination of ligands through oxygen and sulphur atoms upon thioenolization induced delocalization. Complexes adopt cis-configuration in the solid state. Both the complexes and their respective ligands were screened in vitro for antiamoebic activity against HM1:1MSS strain of Entamoeba histolytica by microdilution method and cell viability in response to drugs was checked by using MTT assay. The IC50 values in the range 0.30-0.80 μM for ligands as well as complexes compared to 1.40 for metronidazole along with their similar inhibitory effect on cell viability of HEK293 cells like metronidazole make them promising future antiamoebic drugs.

  8. Determination of anti-giardial activity in vitro by means of soluble formazan production.

    PubMed

    Wright, C W; Melwani, S I; Phillipson, J D; Warhurst, D C

    1992-01-01

    A new microplate assay for the determination of activity in vitro against Giardia intestinalis has been developed in which viability is measured by soluble formazan production from a tetrazolium reagent. Metabolic reduction of the latter gives rise to a coloured product which may be determined directly by optical density measurement. Using this method the anti-giardial activities of more than 20 anti-microbial compounds have been assessed. The results obtained with a number of known anti-giardial agents, including metronidazole (50% inhibitory concentration [IC50] = 2.98 microM) and furazolidone (IC50 = 4.14 microM), compare well with previously published data; mepacrine, however, was found to produce a biphasic dose-response curve from which two IC50 values (0.816 and 6.83 microM) were obtained. This method provides a convenient means by which the search for new anti-giardial agents may be facilitated.

  9. Protective effect of p-methoxycinnamic acid, an active phenolic acid against 1,2-dimethylhydrazine-induced colon carcinogenesis: modulating biotransforming bacterial enzymes and xenobiotic metabolizing enzymes.

    PubMed

    Gunasekaran, Sivagami; Venkatachalam, Karthikkumar; Jeyavel, Kabalimoorthy; Namasivayam, Nalini

    2014-09-01

    Objective of the study is to evaluate the modifying potential of p-methoxycinnamic acid (p-MCA), an active rice bran phenolic acid on biotransforming bacterial enzymes and xenobiotic metabolizing enzymes in 1,2-dimethylhydrazine-induced rat colon carcinogenesis. 48 male albino wistar rats were divided into six groups. Group1 (control) received modified pellet diet and 0.1 % carboxymethylcellulose; group2 received modified pellet diet along with p-MCA (80 mg/kg b.wt. p.o.) everyday for 16 weeks; groups 3-6 received 1,2-dimethylhydrazine (DMH) (20 mg/kg b.wt.) subcutaneous injection once a week for the first 4 weeks, while groups 4-6 received p-MCA at three different doses of 20, 40 and 80 mg/kg b.wt. p.o. everyday for 16 weeks. A significant increase in carcinogen-activating enzymes (cytochrome P450, cytochrome b5, cytochrome P4502E1, NADH-cytochrome-b5-reductase and NADPH-cytochrome-P450 reductase) with concomitant decrease in phaseII enzymes, DT-Diaphorase, glutathione S-transferase, UDP-glucuronyl-transferase and gamma glutamyltransferase were observed in group3 compared to control. DMH treatment significantly increased the activities of feacal and colonic bacterial enzymes (β-glucosidase, β-galactosidase, β-glucuronidase, nitroreductase, sulphatase and mucinase). p-MCA supplementation (40 mg/kg b.wt) to carcinogen exposed rats inhibited these enzymes, which were near those of control rats. The formation of dysplastic aberrant crypt foci in the colon and the histopathological observations of the liver also supports our biochemical findings. p-MCA (40 mg/kg b.wt.) offers remarkable modulating efficacy of biotransforming bacterial and xenobiotic metabolizing enzymes in colon carcinogenesis.

  10. Amoebicidal Activity of Essential Oil of Dysphania ambrosioides (L.) Mosyakin & Clemants in an Amoebic Liver Abscess Hamster Model.

    PubMed

    Avila-Blanco, Manuel Enrique; Rodríguez, Martín Gerardo; Moreno Duque, José Luis; Muñoz-Ortega, Martin; Ventura-Juárez, Javier

    2014-01-01

    Amebiasis is a parasitic disease that extends worldwide and is a public health problem in developing countries. Metronidazole is the drug recommended in the treatment of amebiasis, but its contralateral effects and lack of continuity of treatment induce low efficiency, coupled with the appearance of resistant amoebic strains. Therefore, the search of new compounds with amoebicidal activity is urgent and important. In this study, we evaluated the in vitro and in vivo antiamoebic activity of the essential oil Dysphania ambrosioides (L.) Mosyakin & Clemants. It exhibited an IC50 = 0.7 mg/mL against trophozoites. The oral administration of essential oil (8 mg/kg and 80 mg/kg) to hamster infected with Entamoeba histolytica reverted the infection. Ascaridole was identified as the main component of essential oil of D. ambrosioides. The identification of amoebicidal activity of Ascaridole gives support to the traditional use. Further studies with Ascaridole will be carried out to understand the mechanism involved.

  11. In vitro activity of 'Mexican Arnica' Heterotheca inuloides Cass natural products and some derivatives against Giardia intestinalis.

    PubMed

    Rodríguez-Chávez, José Luis; Rufino-González, Yadira; Ponce-Macotela, Martha; Delgado, Guillermo

    2015-04-01

    Giardiasis is a gastrointestinal disease that affects humans and other animals caused by parasitic protists of the genus Giardia. Giardia intestinalis (Syn. Giardia lamblia; Giardia duodenalis) infections can cause acute or chronic diarrhoea, dehydration, abdominal discomfort and weight loss. Metronidazole is the most widely used drug for treating giardiasis. Although effective, metronidazol has undesirable secondary effects. Plants used in traditional medicine as antidiarrhoeals or antiparasitics may represent alternative sources for new compounds to treat giardiasis. Heterotheca inuloides Cass. (Asteraceae/Compositae) plant is widely used in Mexican traditional medicine. The following secondary metabolites were isolated from H. inuloides flowers: 7-hydroxy-3,4-dihydrocadalene (1), 7-hydroxycadalene (2), 3,7-dihydroxy-3(4H)-isocadalen-4-one (3), 1R,4R-hydroxy-1,2,3,4-tetrahydrocadalen-15-oic acid (4), quercetin (5), quercetin-3,7,3'-trimethyl ether (6), quercetin-3,7,3',4'-tetramethyl ether (7) and eriodictyol-7,4'-dimethyl ether (8). The activity of these compounds against Giardia intestinalis trophozoites was assessed in vitro as was the activity of the semisynthetic compounds 7-acetoxy-3,4-dihydrocadalene (9), 7-benzoxy-3,4-dihydrocadalene (10), 7-acetoxycadalene (11), 7-benzoxycadalene (12), quercetin pentaacetate (13) and 7-hydroxycalamenene (14). Among these, 7-hydroxy-3,4-dihydrocadalene (1) and 7-hydroxycalamenene (14) were the most active, whereas the remaining compounds showed moderate or no activity. The G. intestinalis trophozoites exposed to compound 1 showed marked changes in cellular architecture along with ultrastructural disorganization. The aim of this study was to evaluate the giardicidal activity of selected H. inuloides metabolites and some semisynthetic derivatives using an in vitro experimental model of giardiasis.

  12. Potential amoebicidal activity of hydrazone derivatives: synthesis, characterization, electrochemical behavior, theoretical study and evaluation of the biological activity.

    PubMed

    Toledano-Magaña, Yanis; García-Ramos, Juan Carlos; Navarro-Olivarria, Marisol; Flores-Alamo, Marcos; Manzanera-Estrada, Mayra; Ortiz-Frade, Luis; Galindo-Murillo, Rodrigo; Ruiz-Azuara, Lena; Meléndrez-Luevano, Ruth Ma; Cabrera-Vivas, Blanca M

    2015-05-29

    Four new hydrazones were synthesized by the condensation of the selected hydrazine and the appropriate nitrobenzaldehyde. A complete characterization was done employing 1H- and 13C-NMR, electrochemical techniques and theoretical studies. After the characterization and electrochemical analysis of each compound, amoebicidal activity was tested in vitro against the HM1:IMSS strain of Entamoeba histolytica. The results showed the influence of the nitrobenzene group and the hydrazone linkage on the amoebicidal activity. meta-Nitro substituted compound 2 presents a promising amoebicidal activity with an IC50 = 0.84 μM, which represents a 7-fold increase in cell growth inhibition potency with respect to metronidazole (IC50 = 6.3 μM). Compounds 1, 3, and 4 show decreased amoebicidal activity, with IC50 values of 7, 75 and 23 µM, respectively, as a function of the nitro group position on the aromatic ring. The observed differences in the biological activity could be explained not only by the redox potential of the molecules, but also by their capacity to participate in the formation of intra- and intermolecular hydrogen bonds. Redox potentials as well as the amoebicidal activity can be described with parameters obtained from the DFT analysis.

  13. Activation of formylmethanofurna synthesis in cell extracts of Methanobacterium thermoautotrophicum

    SciTech Connect

    Bobik, T.A.; Wolfe, R.S. )

    1989-03-01

    In cell extracts of Methanobacterium thermoautotrophicum, formylmethanofuran (formyl-MFR) synthesis (an essential CO{sub 2} fixation reaction that is an early step in CO{sub 2} reduction to methane) is subject to a complex activation that involves a heterodisulfide of coenzyme M and N-(7-mercaptoheptanoyl)threonine O{sup 3}-phosphate (CoM-S-S-HTP). In this paper we report that titanium(III) citrate, a low-potential reducing agent, stimulated CO{sub 2} reduction to methane and activated formyl-MFR synthesis in cell extracts. Titanium(III) citrate functioned as the sole source of electrons for formyl-MFR synthesis and enabled this reaction to occur independently of CoM-S-S-HTP. In addition, CoM-S-S-HTP was found to activate an unknown electron carrier that reduced metronidazole. The activation of formyl-MFR synthesis by CoM-S-S-HTP may involve the activation of a low-potential electron carrier.

  14. Effect of nitroreduction on the alkylating reactivity and cytotoxicity of the 2,4-dinitrobenzamide-5-aziridine CB 1954 and the corresponding nitrogen mustard SN 23862: distinct mechanisms of bioreductive activation.

    PubMed

    Helsby, Nuala A; Wheeler, S James; Pruijn, Frederik B; Palmer, Brian D; Yang, Shangjin; Denny, William A; Wilson, William R

    2003-04-01

    The dinitrobenzamide aziridine CB 1954 (1) and its nitrogen mustard analogue SN 23862 (6) are prodrugs that are activated by enzymatic nitroreduction in tumors. Bioactivation of 1 is considered to be due to reduction of its 4-nitro group to the hydroxylamine and subsequent formation of the N-acetoxy derivative; this acts as a reactive center, in concert with the aziridine moiety, to provide a bifunctional DNA cross-linking agent (Knox model). It is currently unclear whether bioactivation of 6 occurs by the same mechanism or results from the electronic effects of nitroreduction on reactivity of the nitrogen mustard moiety. To discriminate between these mechanisms, we have synthesized the hydroxylamine and amine derivatives of 1 and 6, plus related compounds, and determined their alkylating reactivities in aqueous solution, using LC/MS to identify reaction pathways. The relationships between substituent electronic effects, reactivity, and cytotoxicity were determined using the UV4 cell line, which is defective in nucleotide excision repair (thus avoiding differences in repair kinetics). Alkylating reactivity correlated with the electron-donating character of the ortho or para substituent in the case of the mustards, with a less marked electronic effect for the aziridines. Importantly, there was a highly significant linear relationship between cytotoxic potency and alkylating reactivity in both the aziridine and the mustard series, with the notable exception of 4, the 4-hydroxylamine of 1, which was 300-fold more toxic than predicted by this relationship. This demonstrates that the high potency of 4 does not result from activation of the aziridine ring, supporting the Knox model. The single-step bioactivation of 6, to amino or hydroxylamine metabolites with similar potency to 4, is a potential advantage in the use of dinitrobenzamide mustards as prodrugs for activation by nitroreductases.

  15. Chemoselective Nitro Group Reduction and Reductive Dechlorination Initiate Degradation of 2-Chloro-5-Nitrophenol by Ralstonia eutropha JMP134

    PubMed Central

    Schenzle, Andreas; Lenke, Hiltrud; Spain, Jim C.; Knackmuss, Hans-Joachim

    1999-01-01

    Ralstonia eutropha JMP134 utilizes 2-chloro-5-nitrophenol as a sole source of nitrogen, carbon, and energy. The initial steps for degradation of 2-chloro-5-nitrophenol are analogous to those of 3-nitrophenol degradation in R. eutropha JMP134. 2-Chloro-5-nitrophenol is initially reduced to 2-chloro-5-hydroxylaminophenol, which is subject to an enzymatic Bamberger rearrangement yielding 2-amino-5-chlorohydroquinone. The chlorine of 2-amino-5-chlorohydroquinone is removed by a reductive mechanism, and aminohydroquinone is formed. 2-Chloro-5-nitrophenol and 3-nitrophenol induce the expression of 3-nitrophenol nitroreductase, of 3-hydroxylaminophenol mutase, and of the dechlorinating activity. 3-Nitrophenol nitroreductase catalyzes chemoselective reduction of aromatic nitro groups to hydroxylamino groups in the presence of NADPH. 3-Nitrophenol nitroreductase is active with a variety of mono-, di-, and trinitroaromatic compounds, demonstrating a relaxed substrate specificity of the enzyme. Nitrosobenzene serves as a substrate for the enzyme and is converted faster than nitrobenzene. PMID:10347008

  16. Chemoselective nitro group reduction and reductive dechlorination initiate degradation of 2-chloro-5-nitrophenol by Ralstonia eutropha JMP134

    SciTech Connect

    Schenzle, A.; Lenke, H.; Knackmuss, H.J.; Spain, J.C.

    1999-06-01

    Ralstonia eutropha JMP134 utilizes 2-chloro-5-nitrophenol as a sole source of nitrogen, carbon, and energy. The initial steps for degradation of 2-chloro-5-nitrophenol are analogous to those of 3-nitrophenol degradation in R. eutropha JMP134, 2-chloro-5-nitrophenol is initially reduced to 2-chloro-5-hydroxylaminophenol, which is subject to an enzymatic Bamberger rearrangement yielding 2-amino-5-chlorohydroquinone. The chlorine of 2-amino-5-chlorohydroquinone is removed by a reductive mechanism, and aminohydroquinone is formed. 2-Chloro-5-nitrophenol and 3-nitrophenol induce the expression of 3-nitrophenol nitroreductase, of 3-hydroxylaminophenol mutase, and of the dechlorinating activity. 3-Nitrophenol nitroreductase catalyzes chemoselective reduction of aromatic nitro groups to hydroxylamino groups in the presence of NADPH. 3-Nitrophenol nitroreductase is active with a variety of mono-, di-, and trinitroaromatic compounds, demonstrating a relaxed substrate specificity of the enzyme. Nitrosobenzene serves as a substrate for the enzyme and is converted faster than nitrobenzene.

  17. Relationship between free radicals produced by entamoeba histolytica and its proteases complex activity.

    PubMed

    Crisóstomo-Vázquez, M P; Cervantes-Cervantes, M P; Jiménez-Cardoso, E; Muñoz-Sánchez, J L

    2002-01-01

    Entamoeba histolytica is a parasite which causes health problems and there has been many approaches to know what is the factor causing its pathogenicity. In the present work, we assayed if the production of free radicals by the amoeba, has a relationship with the proteases activity. When we test the DMSO action (free radicals quenching activity) the specific activity of the proteases complex of the parasite were affected also. At 33.3% (V/V) concentration of DMSO it was present a maximal decrease of the initial activity (about 46% decrease), for to a higher concentrations existing a trend to recuperate the original activity, suggesting that the free radicals are an important factor for the hydrolysis grade of the protein substrate. All the differences except those between 46.7 and 66.6%, were significantly different compared with the control without any addition. The effects of Probucol and Probucol plus DMSO, compared to those caused by Metronidazol (MZ). We can observe that the quenchers caused a decrease on proteases activity similar to that of MZ (which is an antiparasite drug) and it was of c.a. 58% of activity decrease. These data suggest that the action of both, free radicals and proteases complex of Entamoeba histolytica, can account for the pathogenicity of the parasite.

  18. Mesoporous mixed-phase Ga{sub 2}O{sub 3}: Green synthesis and enhanced photocatalytic activity

    SciTech Connect

    Liu, Jin; Zhang, Gaoke

    2015-08-15

    Highlights: • Mixed-phase Ga{sub 2}O{sub 3} was synthesized by a facile and green method. • Mixed-phase Ga{sub 2}O{sub 3} exhibited good photocatalytic activity and stability. • The reactive species in the photocatalytic process were investigated. - Abstract: Mesoporous mixed-phase Ga{sub 2}O{sub 3} was synthesized by calcining the GaOOH precursor. The composition, crystal phase and microstructures of Ga{sub 2}O{sub 3} were characterized in detail. The phase composition of the as-prepared Ga{sub 2}O{sub 3} depended on the calcination temperature and the mixed-phase Ga{sub 2}O{sub 3} was obtained at 600–700 °C. As compared to the pure-phase α-Ga{sub 2}O{sub 3} and β-Ga{sub 2}O{sub 3}, the mixed-phase Ga{sub 2}O{sub 3} exhibited an enhanced photocatalytic property for the degradation of metronidazole solution. The heterojunction in the mixed-phase Ga{sub 2}O{sub 3} was beneficial to the separation of photogenerated electrons and holes. Moreover, the mixed-phase Ga{sub 2}O{sub 3} possessed mesopore structure, which increased more reaction sites and was in favor of the contact of metronidazole molecules with reaction sites. The recycling experiments show that the mixed-phase Ga{sub 2}O{sub 3} has good stability and can be separated easily from the reaction system.

  19. Diarylacylhydrazones: Clostridium-Selective Antibacterials with Activity Against Stationary-Phase Cells

    PubMed Central

    Casadei, Gabriele; Bremner, John B.; Lewis, Kim; Kelso, Michael J.

    2014-01-01

    Current antibiotics for treating Clostridium difficile infections (CDI), i.e. metronidazole, vancomycin and more recently fidaxomicin, are mostly effective but treatment failure and disease relapse remain as significant clinical problems. The shortcomings of these agents are attributed to their low selectivity for C. difficile over normal gut microflora and their ineffectiveness against C. difficile spores. This paper reports that certain diarylacylhydrazones identified during a high-throughput screening/counter-screening campaign show selective activity against two Clostridium species (C. difficile and C. perfringens) over common gut commensals. Representative examples are shown to possess activity similar to vancomycin against clinical C. difficile strains and to kill stationary-phase C. difficile cells, which are responsible for spore production. Structure-activity relationships with additional synthesised analogues suggested a protonophoric mechanism may play a role in the observed activity/selectivity and this was supported by the well-known protonophore carbonyl cyanide m-chlorophenyl hydrazone (CCCP) showing selective anti-Clostridium effects and activity similar to diarylacylhydrazones against stationary-phase C. difficile cells. Two diarylacylhydrazones were shown to be non-toxic towards human FaDu and Hep G2 cells indicating that further studies with the class are warranted towards new drugs for CDI. PMID:24360560

  20. Activity of the investigational fluoroquinolone finafloxacin and seven other antimicrobial agents against 114 obligately anaerobic bacteria.

    PubMed

    Genzel, G H; Stubbings, W; Stîngu, C S; Labischinski, H; Schaumann, R

    2014-11-01

    The activity of finafloxacin against 73 strains of the Bacteroides fragilis group, 10 other Gram-negative anaerobic rods and 31 Clostridium difficile strains was determined by the broth microdilution technique. The activity was compared with that of moxifloxacin, levofloxacin, ciprofloxacin, clindamycin, imipenem, piperacillin/tazobactam and metronidazole. MIC(50/90) values (minimum inhibitory concentration, in μg/mL, at which 50% and 90% of the isolates tested are inhibited, respectively) for finafloxacin for the different species were determined: B. fragilis group, 0.5/2; other Gram-negative rods, 0.06/0.25; and C. difficile, 4/16. Furthermore, the MICs against 11 selected B. fragilis strains were determined under acidic conditions and resulted in MIC(50/90) values for finafloxacin of 0.25/4 μg/mL. Thus, finafloxacin shows promising activity against several pathogenic species of anaerobes. Furthermore, finafloxacin has increased activity against selected B. fragilis strains under acidic conditions compared with activity at neutral pH.

  1. In vitro antagonistic activity of Lactobacillus casei against Helicobacter pylori

    PubMed Central

    Enany, Shymaa; Abdalla, Salah

    2015-01-01

    Helicobacter pylori is one of the most common causes of chronic infections in humans. Curing H. pylori infection is difficult because of the habitat of the organism below the mucus adherent layer of gastric mucosa. Lactobacilli are known as acid-resistant bacteria and can remain in stomach for a long time than any other organism, we aimed in this study to examine the efficacy of Lactobacillus casei as a probiotic against H. pylori in humans. Particularly, L. casei was opted as it is considered to be one of the widely used probiotics in dairy products. One hundred and seven strains of H. pylori were isolated from dyspeptic patients and were tested for their antibiotic susceptibility to metronidazole (MTZ), clarithromycin (CLR), tetracycline (TET), and amoxicillin (AMX) by the disc diffusion method. The strains were examined for their susceptibility toward L. casei - present in fermented milk products - by well diffusion method. It was found that 74.7% strains were resistant to MTZ; 1.8% to MTZ, TET, and CLR; 3.7% to MTZ and CLR; 4.6% to MTZ and TET; and 0.9% were resistant to MTZ, TET, and AMX. The antibacterial activity of L. casei against H. pylori was determined on all the tested H. pylori isolates including antibiotic resistant strains with different patterns. Our study proposed the use of probiotics for the treatment of H. pylori infection as an effective approach. PMID:26691482

  2. Alkaloids: an overview of their antibacterial, antibiotic-enhancing and antivirulence activities.

    PubMed

    Cushnie, T P Tim; Cushnie, Benjamart; Lamb, Andrew J

    2014-11-01

    With reports of pandrug-resistant bacteria causing untreatable infections, the need for new antibacterial therapies is more pressing than ever. Alkaloids are a large and structurally diverse group of compounds that have served as scaffolds for important antibacterial drugs such as metronidazole and the quinolones. In this review, we highlight other alkaloids with development potential. Natural, semisynthetic and synthetic alkaloids of all classes are considered, looking first at those with direct antibacterial activity and those with antibiotic-enhancing activity. Potent examples include CJ-13,136, a novel actinomycete-derived quinolone alkaloid with a minimum inhibitory concentration of 0.1 ng/mL against Helicobacter pylori, and squalamine, a polyamine alkaloid from the dogfish shark that renders Gram-negative pathogens 16- to >32-fold more susceptible to ciprofloxacin. Where available, information on toxicity, structure-activity relationships, mechanisms of action and in vivo activity is presented. The effects of alkaloids on virulence gene regulatory systems such as quorum sensing and virulence factors such as sortases, adhesins and secretion systems are also described. The synthetic isoquinoline alkaloid virstatin, for example, inhibits the transcriptional regulator ToxT in Vibrio cholerae, preventing expression of cholera toxin and fimbriae and conferring in vivo protection against intestinal colonisation. The review concludes with implications and limitations of the described research and directions for future research.

  3. In-vitro activity of solithromycin against anaerobic bacteria from the normal intestinal microbiota.

    PubMed

    Weintraub, Andrej; Rashid, Mamun-Ur; Nord, Carl Erik

    2016-12-01

    Solithromycin is a novel fluoroketolide with high activity against bacteria associated with community-acquired respiratory tract infections as well as gonorrhea. However, data on the activity of solithromycin against anaerobic bacteria from the normal intestinal microbiota are scarce. In this study, 1024 Gram-positive and Gram-negative anaerobic isolates from the normal intestinal microbiota were analyzed for in-vitro susceptibility against solithromycin and compared to azithromycin, amoxicillin/clavulanic acid, ceftriaxone, metronidazole and levofloxacin by determining the minimum inhibitory concentration (MIC). Solithromycin was active against Bifidobacteria (MIC50, 0.008 mg/L) and Lactobacilli (MIC50, 0.008 mg/L). The MIC50 for Clostridia, Bacteroides, Prevotella and Veillonella were 0.5, 0.5, 0.125 and 0.016 mg/L, respectively. Gram-positive anaerobes were more susceptible to solithromycin as compared to the other antimicrobials tested. The activity of solithromycin against Gram-negative anaerobes was equal or higher as compared to other tested agents.

  4. Evaluation of Chlorinated Solvent Removal Efficiency Among Three Wetland Plant Species: A Mesocom Study

    DTIC Science & Technology

    2006-03-01

    per gram of dry soil (Bouwer, 1992). ATP extraction also indicates that around 10% of the cells in the subsurface are metabolically active (Bouwer...phytodegradation, phytostabilization and phytovolatilization (Lunney, 2004). Phytoextraction is the process in which plants extract pollutants and degraded...nitroreductase, peroxidase, lactase , and nitrilase (Schnoor, 1995). Plants could also directly uptake pollutants. But direct uptake is

  5. Caatinga plants: Natural and semi-synthetic compounds potentially active against Trichomonas vaginalis.

    PubMed

    Vieira, Patrícia de Brum; Silva, Nícolas Luiz Feijó; da Silva, Gloria Narjara Santos; Silva, Denise Brentan; Lopes, Norberto Peporine; Gnoatto, Simone Cristina Baggio; da Silva, Márcia Vanusa; Macedo, Alexandre José; Bastida, Jaume; Tasca, Tiana

    2016-05-01

    Trichomonas vaginalis causes trichomoniasis; the most common but overlooked non-viral sexually transmitted disease worldwide. The treatment is based at 5'-nitroimidazoles, however, failure are related to resistance of T. vaginalis to chemotherapy. Caatinga is a uniquely Brazilian region representing a biome with type desert vegetation and plants present diverse biological activity, however, with few studies. The aim of this study was to investigate the activity against T. vaginalis of different plants from Caatinga and identify the compounds responsible by the activity. A bioguided fractionation of Manilkara rufula was performed and four major compounds were identified: caproate of α-amyrin (1b), acetate of β-amyrin (2a), caproate of β-amyrin (2b), and acetate of lupeol (3a). In addition, six derivatives of α-amyrin (1), β-amyrin (2) and lupeol (3) were synthesized and tested against the parasite. Ursolic acid (5) reduced about 98% of parasite viability after 2h of incubation and drastic ultrastructural alterations were observed by scanning electron microscopy. Moreover, 5 presented high cytotoxicity to HMVII and HeLa cell line and low cytotoxicity against Vero line at 50 μM (MIC against the parasite). Metronidazole effect against T. vaginalis resistant isolate was improved when in association with 5.

  6. In vitro activity of artemisone and artemisinin derivatives against extracellular and intracellular Helicobacter pylori.

    PubMed

    Sisto, Francesca; Scaltrito, Maria Maddalena; Masia, Carla; Bonomi, Arianna; Coccè, Valentina; Marano, Giuseppe; Haynes, Richard K; Miani, Alessandro; Farronato, Giampietro; Taramelli, Donatella

    2016-07-01

    The in vitro activity of the new artemisinin derivative artemisone as well as other molecules of the same class against Helicobacter pylori and their effects when combined with standard antibiotics were evaluated. Since H. pylori can be internalised into gastric epithelial cells, the effects of artemisinin, dihydroartemisinin and artemisone against intracellular H. pylori were also investigated. Bacteriostatic [minimum inhibitory concentration (MIC)] and bactericidal [minimum bactericidal concentration (MBC)] activities were assessed against 24 clinical strains of H. pylori with different antibiotics susceptibilities. Artemisone showed MIC50 and MIC90 values of 0.25 mg/L and 0.5 mg/L, respectively, and an MBC50 value of 0.5 mg/L. Artemisone was synergistic with amoxicillin in 60% of strains, with clarithromycin in 40% and with metronidazole in 20%. There was no interaction between artemisone and omeprazole or bismuth citrate. Against intracellular H. pylori, only dihydroartemisinin at 2× MIC caused a 1 log10 CFU decrease after 18 h and 24 h of incubation. This is the first demonstration in vitro of the activity of artemisinin derivatives against intracellular H. pylori and indicates that artemisone has the potential to be efficacious for the treatment of H. pylori infection, especially in combination with antibiotics.

  7. Pharmacokinetics and pharmacodynamics of the nitroimidazole antimicrobials.

    PubMed

    Lamp, K C; Freeman, C D; Klutman, N E; Lacy, M K

    1999-05-01

    Metronidazole, the prototype nitroimidazole antimicrobial, was originally introduced to treat Trichomonas vaginalis, but is now used for the treatment of anaerobic and protozoal infections. The nitroimidazoles are bactericidal through toxic metabolites which cause DNA strand breakage. Resistance, both clinical and microbiological, has been described only rarely. Metronidazole given orally is absorbed almost completely, with bioavailability > 90% for tablets; absorption is unaffected by infection. Rectal and intravaginal absorption are 67 to 82%, and 20 to 56%, of the dose, respectively. Metronidazole is distributed widely and has low protein binding (< 20%). The volume of distribution at steady state in adults is 0.51 to 1.1 L/kg. Metronidazole reaches 60 to 100% of plasma concentrations in most tissues studied, including the central nervous system, but does not reach high concentrations in placental tissue. Metronidazole is extensively metabolised by the liver to 5 metabolites. The hydroxy metabolite has biological activity of 30 to 65% and a longer elimination half-life than the parent compound. The majority of metronidazole and its metabolites are excreted in urine and faeces, with less than 12% excreted unchanged in urine. The pharmacokinetics of metronidazole are unaffected by acute or chronic renal failure, haemodialysis, continuous ambulatory peritoneal dialysis, age, pregnancy or enteric disease. Renal dysfunction reduces the elimination of metronidazole metabolites; however, no toxicity has been documented and dosage alterations are unnecessary. Liver disease leads to a decreased clearance of metronidazole and dosage reduction is recommended. Recent pharmacodynamic studies of metronidazole have demonstrated activity for 12 to 24 hours after administration of metronidazole 1 g. The post-antibiotic effect of metronidazole extends beyond 3 hours after the concentration falls below the minimum inhibitory concentration (MIC). The concentration

  8. Amoebicidal Activity of Essential Oil of Dysphania ambrosioides (L.) Mosyakin & Clemants in an Amoebic Liver Abscess Hamster Model

    PubMed Central

    Ávila-Blanco, Manuel Enrique; Rodríguez, Martín Gerardo; Moreno Duque, José Luis; Muñoz-Ortega, Martin; Ventura-Juárez, Javier

    2014-01-01

    Amebiasis is a parasitic disease that extends worldwide and is a public health problem in developing countries. Metronidazole is the drug recommended in the treatment of amebiasis, but its contralateral effects and lack of continuity of treatment induce low efficiency, coupled with the appearance of resistant amoebic strains. Therefore, the search of new compounds with amoebicidal activity is urgent and important. In this study, we evaluated the in vitro and in vivo antiamoebic activity of the essential oil Dysphania ambrosioides (L.) Mosyakin & Clemants. It exhibited an IC50 = 0.7 mg/mL against trophozoites. The oral administration of essential oil (8 mg/kg and 80 mg/kg) to hamster infected with Entamoeba histolytica reverted the infection. Ascaridole was identified as the main component of essential oil of D. ambrosioides. The identification of amoebicidal activity of Ascaridole gives support to the traditional use. Further studies with Ascaridole will be carried out to understand the mechanism involved. PMID:24757495

  9. Pineal Photoreceptor Cells Are Required for Maintaining the Circadian Rhythms of Behavioral Visual Sensitivity in Zebrafish

    PubMed Central

    Li, Xinle; Montgomery, Jake; Cheng, Wesley; Noh, Jung Hyun; Hyde, David R.; Li, Lei

    2012-01-01

    In non-mammalian vertebrates, the pineal gland functions as the central pacemaker that regulates the circadian rhythms of animal behavior and physiology. We generated a transgenic zebrafish line [Tg(Gnat2:gal4-VP16/UAS:nfsB-mCherry)] in which the E. coli nitroreductase is expressed in pineal photoreceptor cells. In developing embryos and young adults, the transgene is expressed in both retinal and pineal photoreceptor cells. During aging, the expression of the transgene in retinal photoreceptor cells gradually diminishes. By 8 months of age, the Gnat2 promoter-driven nitroreductase is no longer expressed in retinal photoreceptor cells, but its expression in pineal photoreceptor cells persists. This provides a tool for selective ablation of pineal photoreceptor cells, i.e., by treatments with metronidazole. In the absence of pineal photoreceptor cells, the behavioral visual sensitivity of the fish remains unchanged; however, the circadian rhythms of rod and cone sensitivity are diminished. Brief light exposures restore the circadian rhythms of behavioral visual sensitivity. Together, the data suggest that retinal photoreceptor cells respond to environmental cues and are capable of entraining the circadian rhythms of visual sensitivity; however, they are insufficient for maintaining the rhythms. Cellular signals from the pineal photoreceptor cells may be required for maintaining the circadian rhythms of visual sensitivity. PMID:22815753

  10. Hydrogenosome Metabolism Is the Key Target for Antiparasitic Activity of Resveratrol against Trichomonas vaginalis

    PubMed Central

    Mallo, Natalia; Lamas, Jesús

    2013-01-01

    Metronidazole (MDZ) and related 5-nitroimidazoles are the recommended drugs for treatment of trichomoniasis, a sexually transmitted disease caused by the protozoan parasite Trichomonas vaginalis. However, novel treatment options are needed, as recent reports have claimed resistance to these drugs in T. vaginalis isolates. In this study, we analyzed for the first time the in vitro effects of the natural polyphenol resveratrol (RESV) on T. vaginalis. At concentrations of between 25 and 100 μM, RESV inhibited the in vitro growth of T. vaginalis trophozoites; doses of 25 μM exerted a cytostatic effect, and higher doses exerted a cytotoxic effect. At these concentrations, RESV caused inhibition of the specific activity of a 120-kDa [Fe]-hydrogenase (Tvhyd). RESV did not affect Tvhyd gene expression and upregulated pyruvate-ferredoxin oxidoreductase (a hydrogenosomal enzyme) gene expression only at a high dose (100 μM). At doses of 50 to 100 μM, RESV also caused overexpression of heat shock protein 70 (Hsp70), a protective protein found in the hydrogenosome of T. vaginalis. The results demonstrate the potential of RESV as an antiparasitic treatment for trichomoniasis and suggest that the mechanism of action involves induction of hydrogenosomal dysfunction. In view of the results, we propose hydrogenosomal metabolism as a key target in the design of novel antiparasitic drugs. PMID:23478970

  11. Hydrogenosome metabolism is the key target for antiparasitic activity of resveratrol against Trichomonas vaginalis.

    PubMed

    Mallo, Natalia; Lamas, Jesús; Leiro, José M

    2013-06-01

    Metronidazole (MDZ) and related 5-nitroimidazoles are the recommended drugs for treatment of trichomoniasis, a sexually transmitted disease caused by the protozoan parasite Trichomonas vaginalis. However, novel treatment options are needed, as recent reports have claimed resistance to these drugs in T. vaginalis isolates. In this study, we analyzed for the first time the in vitro effects of the natural polyphenol resveratrol (RESV) on T. vaginalis. At concentrations of between 25 and 100 μM, RESV inhibited the in vitro growth of T. vaginalis trophozoites; doses of 25 μM exerted a cytostatic effect, and higher doses exerted a cytotoxic effect. At these concentrations, RESV caused inhibition of the specific activity of a 120-kDa [Fe]-hydrogenase (Tvhyd). RESV did not affect Tvhyd gene expression and upregulated pyruvate-ferredoxin oxidoreductase (a hydrogenosomal enzyme) gene expression only at a high dose (100 μM). At doses of 50 to 100 μM, RESV also caused overexpression of heat shock protein 70 (Hsp70), a protective protein found in the hydrogenosome of T. vaginalis. The results demonstrate the potential of RESV as an antiparasitic treatment for trichomoniasis and suggest that the mechanism of action involves induction of hydrogenosomal dysfunction. In view of the results, we propose hydrogenosomal metabolism as a key target in the design of novel antiparasitic drugs.

  12. Anti-Helicobacter pylori and urease inhibition activities of some traditional medicinal plants.

    PubMed

    Amin, Muhammad; Anwar, Farooq; Naz, Fauqia; Mehmood, Tahir; Saari, Nazamid

    2013-02-07

    Different parts of Acacia nilotica (L.) Delile, Calotropis procera (Aiton) W.T. Aiton, Adhatoda vasica Nees, Fagoniaar abica L. and Casuarina equisetifolia L. are traditionally used in folk medicine for the treatment of a variety of common ailments like nausea, cold, cough, asthma, fevers, diarrhea, sore throat, swelling, etc. The present study was aimed to evaluate the anti-Helicobacter pylori and urease inhibition activities of extracts produced from the above selected medicinal plants native to Soon Valley (home to an old civilization) in the Punjab province of Pakistan. Methanol, acetone and water extracts of the plants were evaluated for anti-bacterial activity against thirty four clinical isolates and two reference strains of H. pylori. Minimum inhibitory concentrations (MICs) of the extracts were determined using the agar dilution method and compared with some standard antibiotics like amoxicillin (AMX), clarithromycin (CLA), tetracycline (TET) and metronidazole (MNZ), used in the triple therapy for H. pylori eradication. H. pylori urease inhibition activity of the extracts was assessed by the phenol red method, wherein, Lineweaver-Burk plots were used to determine Michaelis-Menten constants for elucidating the mechanism of inhibition. Methanol and acetone extracts from Acacia nilotica and Calotropis procera exhibited stronger anti-H. pylori activity than MNZ, almost comparable activity with TET, but were found to be less potent than AMX and CLT. The rest of the extracts exhibited lower activity than the standard antibiotics used in this study. In the H. pylori urease inhibitory assay, methanol and acetone extracts of Acacia nilotica and Calotropis procera showed significant inhibition. Lineweaver-Burk plots indicated a competitive mechanism for extract of Acacia nilotica, whereas extract of Calotropis procera exhibited a mixed type of inhibition.

  13. Chemical composition of essential oil and anti trichomonas activity of leaf, stem, and flower of Rheum ribes L. extracts

    PubMed Central

    Naemi, Forough; Asghari, Gholamreza; Yousofi, Hossein; Yousefi, Hossein Ali

    2014-01-01

    Objectives: Trichomoniasis is one of the most common sexually transmitted diseases in humans and is caused by the protozoan Trichomonas vaginalis. Nowadays, increasing resistance to drugs such as metronidazole resulted in many problem, so new effective remedies are needed. In this study, we evaluate constituents of essential oil and anti-trichomonas activity of Rheum ribes. Materials and Methods: The essential oil from Rheum ribes L. flower growing wild in Iran was analyzed by GC/MS. The parasites were treated with different extract and fractions of the flower, stem, and leave of the plant. Anti-trichomonas activity was evaluated using an in vitro assay. Results: In all, 19 compounds were identified; palmitic acid [27.08%], n-eicosane [9.9%], n-tetracosane [7.34%], linoleic acid [6.56%], and ethyl linoleate [4.76%] were the main components of the oil. Rheum ribes extracts and fractions concentration dependently inhibited the ability of parasites to growth. This was associated with polarity of solvent used for fractionation and plant parts used for extraction. Conclusion: Findings demonstrate the potential of Rheum ribes extracts as an anti-trichomonas agent for human use. Further studies are required to evaluate its toxicity and safety. PMID:25050317

  14. Expanded therapeutic potential in activity space of next-generation 5-nitroimidazole antimicrobials with broad structural diversity.

    PubMed

    Miyamoto, Yukiko; Kalisiak, Jaroslaw; Korthals, Keith; Lauwaet, Tineke; Cheung, Dae Young; Lozano, Ricardo; Cobo, Eduardo R; Upcroft, Peter; Upcroft, Jacqueline A; Berg, Douglas E; Gillin, Frances D; Fokin, Valery V; Sharpless, K Barry; Eckmann, Lars

    2013-10-22

    Metronidazole and other 5-nitroimidazoles (5-NI) are among the most effective antimicrobials available against many important anaerobic pathogens, but evolving resistance is threatening their long-term clinical utility. The common 5-NIs were developed decades ago, yet little 5-NI drug development has since taken place, leaving the true potential of this important drug class unexplored. Here we report on a unique approach to the modular synthesis of diversified 5-NIs for broad exploration of their antimicrobial potential. Many of the more than 650 synthesized compounds, carrying structurally diverse functional groups, have vastly improved activity against a range of microbes, including the pathogenic protozoa Giardia lamblia and Trichomonas vaginalis, and the bacterial pathogens Helicobacter pylori, Clostridium difficile, and Bacteroides fragilis. Furthermore, they can overcome different forms of drug resistance, and are active and nontoxic in animal infection models. These findings provide impetus to the development of structurally diverse, next-generation 5-NI drugs as agents in the antimicrobial armamentarium, thus ensuring their future viability as primary therapeutic agents against many clinically important infections.

  15. Increased photocatalytic activity of NiO and ZnO in photodegradation of a model drug aqueous solution: Effect of coupling, supporting, particles size and calcination temperature.

    PubMed

    Derikvandi, Hadis; Nezamzadeh-Ejhieh, Alireza

    2017-01-05

    Mechanically ball-mill prepared clinoptilolite nanoparticles (NC) were used for increasing photocatalytic activity of NiO and ZnO as alone and binary systems. The semiconductors were supported onto the zeolite during calcination of Ni(II)-Zn(II)-exchanged NC at different calcinations temperatures. XRD, FTIR, SEM-EDX, X-ray mapping, DRS, TEM and BET techniques were used for characterization of the samples. The calcined catalysts at 400°C for 4h showed the best photocatalytic activity for metronidazole (MNZ) in aqueous solution. The mole ratio of ZnO/NiO affected the photodegradation efficiency because activity of the coupled catalysts depends to the both e/h production and electron scavenging processes. In the used system, NiO acted as e/h production source and ZnO as an electron sink. Red shifts in band gaps of the supported coupled semiconductors was observed whit respect to monocomponent one, confirming formation of nanoparticles of the semiconductors onto the zeolitic bed. The best activities were obtained for the NiO1.3-ZnO1.5/NC (NZ-NC) and NiO0.7-ZnO4.3/NC (NZ3-NC) catalysts at pH 3, 1.2gL(-1) of the catalysts and 1gL(-1) of MNZ.

  16. Antiprotozoal activity against Entamoeba histolytica of plants used in northeast Mexican traditional medicine. Bioactive compounds from Lippia graveolens and Ruta chalepensis.

    PubMed

    Quintanilla-Licea, Ramiro; Mata-Cárdenas, Benito David; Vargas-Villarreal, Javier; Bazaldúa-Rodríguez, Aldo Fabio; Kavimngeles-Hernández, Isvar; Garza-González, Jesús Norberto; Hernández-García, Magda Elizabeth

    2014-12-15

    Amoebiasis caused by Entamoeba histolytica is associated with high morbidity and mortality is becoming a major public health problem worldwide, especially in developing countries. Because of the side-effects and the resistance that pathogenic protozoa build against the standard antiparasitic drugs, e.g., metronidazole, much recent attention has been paid to plants used in traditional medicine around the world in order to find new antiprotozoal agents. We collected 32 plants used in Northeast Mexican traditional medicine and the methanolic extracts of these species were screened for antiprotozoal activity against E. histolytica trophozoites using in vitro tests. Only 18 extracts showed a significant inhibiting activity and among them six plant extracts showed more than 80% growth inhibition against E. histolytica at a concentration of 150 µg/mL and the IC50 values of these extracts were determined. Lippia graveolens Kunth and Ruta chalepensis Pers. showed the more significant antiprotozoal activity (91.54% and 90.50% growth inhibition at a concentration of 150 µg/mL with IC50 values of 59.14 and 60.07 µg/mL, respectively). Bioassay-guided fractionation of the methanolic extracts from these two plants afforded carvacrol (1) and chalepensin (2), respectively, as bioactive compounds with antiprotozoal activity.

  17. Synthesis, characterisation, reactivity and in vitro antiamoebic activity of hydrazone based oxovanadium(IV), oxovanadium(V) and mu-bis(oxo)bis{oxovanadium(V)} complexes.

    PubMed

    Maurya, Mannar R; Agarwal, Shalu; Abid, Mohammad; Azam, Amir; Bader, Cerstin; Ebel, Martin; Rehder, Dieter

    2006-02-21

    Binuclear, mu-bis(oxo)bis{oxovanadium(V)} complexes [(VOL)2(mu-O)2](2 and 7)(where HL are the hydrazones Hacpy-nah I or Hacpy-fah II; acpy = 2-acetylpyridine, nah = nicotinic acid hydrazide and fah = 2-furoic acid hydrazide) were prepared by the reaction of [VO(acac)2] and the ligands in methanol followed by aerial oxidation. The paramagnetic intermediate complexes [VO(acac)(acpy-nah)](1) and [VO(acac)(acpy-fah)](6) have also been isolated. Treatment of [VO(acac)(acpy-nah)] and [VO(acac)(acpy-fah)] with aqueous H2O2 yields the oxoperoxovanadium(V) complexes [VO(O2)(acpy-nah)](3) and [VO(O2)(acpy-fah)](8). In the presence of catechol (H2cat) or benzohydroxamic acid (H2bha), 1 and 6 give the mixed chelate complexes [VO(cat)L](HL =I: 4, HL =II: 9) or [VO(bha)L](HL =I: 5, HL =II: 10). Complexes 4, 5, 9 and 10 slowly convert to the corresponding oxo-mu-oxo species 2 and 7 in DMF solution. Ascorbic acid enhances this conversion under aerobic conditions, possibly through reduction of these complexes with concomitant removal of coordinated catecholate or benzohydroxamate. Acidification of 7 with HCl dissolved in methanol afforded a hydroxo(oxo) complex. The crystal and molecular structure of 2.1.5H2O has been determined, and the structure of 7 re-determined, by single crystal X-ray diffraction. Both of these binuclear complexes contain the uncommon asymmetrical {VO(mu-O)}2 diamond core. The in vitro tests of the antiamoebic activity of ligands I and II and their binuclear complexes 2 and 7 against the protozoan parasite Entamoeba histolytica show that the ligands have no amoebicidal activity while their vanadium complexes 2 and 7 display more effective amoebicidal activity than the most commonly used drug metronidazole (IC50 values are 1.68 and 0.45 microM, respectively vs 1.81 microM for metronidazole). Complexes 2 and 7 catalyse the oxidation of styrene and ethyl benzene effectively. Oxidation of styrene, using H2O2 as an oxidant, gives styrene epoxide, 2

  18. Antichagasic and trichomonacidal activity of 1-substituted 2-benzyl-5-nitroindazolin-3-ones and 3-alkoxy-2-benzyl-5-nitro-2H-indazoles.

    PubMed

    Fonseca-Berzal, Cristina; Ibáñez-Escribano, Alexandra; Reviriego, Felipe; Cumella, José; Morales, Paula; Jagerovic, Nadine; Nogal-Ruiz, Juan José; Escario, José Antonio; da Silva, Patricia Bernardino; Soeiro, Maria de Nazaré C; Gómez-Barrio, Alicia; Arán, Vicente J

    2016-06-10

    Two series of new 5-nitroindazole derivatives, 1-substituted 2-benzylindazolin-3-ones (6-29, series A) and 3-alkoxy-2-benzyl-2H-indazoles (30-37, series B), containing differently functionalized chains at position 1 and 3, respectively, have been synthesized starting from 2-benzyl-5-nitroindazolin-3-one 5, and evaluated against the protozoan parasites Trypanosoma cruzi and Trichomonas vaginalis, etiological agents of Chagas disease and trichomonosis, respectively. Many indazolinones of series A were efficient against different morphological forms of T. cruzi CL Brener strain (compounds 6, 7, 9, 10 and 19-21: IC50 = 1.58-4.19 μM for epimastigotes; compounds 6, 19-21 and 24: IC50 = 0.22-0.54 μM for amastigotes) being as potent as the reference drug benznidazole. SAR analysis suggests that electron-donating groups at position 1 of indazolinone ring are associated with an improved antichagasic activity. Moreover, compounds of series A displayed low unspecific toxicities against an in vitro model of mammalian cells (fibroblasts), which were reflected in high values of the selectivity indexes (SI). Compound 20 was also very efficient against amastigotes from Tulahuen and Y strains of T. cruzi (IC50 = 0.81 and 0.60 μM, respectively), showing low toxicity towards cardiac cells (LC50 > 100 μM). In what concerns compounds of series B, some of them displayed moderate activity against trophozoites of a metronidazole-sensitive isolate of T. vaginalis (35 and 36: IC50 = 9.82 and 7.25 μM, respectively), with low unspecific toxicity towards Vero cells. Compound 36 was also active against a metronidazole-resistant isolate (IC50 = 9.11 μM) and can thus be considered a good prototype for the development of drugs directed to T. vaginalis resistant to 5-nitroimidazoles.

  19. Active-R filter

    DOEpatents

    Soderstrand, Michael A.

    1976-01-01

    An operational amplifier-type active filter in which the only capacitor in the circuit is the compensating capacitance of the operational amplifiers, the various feedback and coupling elements being essentially solely resistive.

  20. The in vitro anti-giardial activity of extracts from plants that are used for self-medication by AIDS patients in southern Thailand.

    PubMed

    Sawangjaroen, N; Subhadhirasakul, S; Phongpaichit, S; Siripanth, C; Jamjaroen, K; Sawangjaroen, K

    2005-01-01

    This study evaluated the anti-giardial activity of chloroform, methanol and water extracts of 12 medicinal plants (39 extracts), commonly used as self medication by AIDS patients in southern Thailand. The plant extracts and a standard drug, metronidazole, were incubated with 2x10(5) trophozoites of Giardia intestinalis per millilitre of growth medium in 96-well tissue culture plates under anaerobic conditions for 24 h. The cultures were examined with an inverted microscope and the minimum inhibitory concentration and the IC50 value for each extract was determined. The chloroform extracts from Alpinia galanga, Boesenbergia pandurata, Eclipta prostrata, Piper betle, Piper chaba, Zingiber zerumbet, and the methanol extracts from B. pandurata and E. prostrata were classified as "active", i.e. with an IC50 of <100 microg/ml, whereas the chloroform extract from Murraya paniculata was classified as being "moderately active". This study shows that extracts from some medicinal plants have potential for use as therapeutic agents against G. intestinalis infections.

  1. Controlled synthesis of T-shaped BiVO4 and enhanced visible light responsive photocatalytic activity

    NASA Astrophysics Data System (ADS)

    Dong, Shuying; Yu, Chongfei; Li, Yukun; Li, Yihui; Sun, Jianhui; Geng, Xiaofei

    2014-03-01

    A novel T-shaped BiVO4 microcrystal photocatalyst was successfully synthesized by the hydrothermal method with the aid of a structure-directing surfactant SDBS in the present study. Having received well characterization with the aid of various techniques and the results showed that the SDBS greatly changed the microstructure of BiVO4, which had a unique T shape and belonged to the monoclinic family. The fast exchange dynamics between the surfactants bound to the Bi3+ seed surface and the free VO3- in the solution significantly increase the rate of heterogeneous nucleation. In addition, the photocatalytic activity of the prepared T-shaped BiVO4 was evaluated by the degradation of Methylene Blue solution under visible light irradiation, 17% and 47% higher decolorization rates than the commercial P25 and BiVO4 synthesized without SDBS, respectively. Meanwhile, it has been found that the degradation kinetics of MB fitted the pseudo-first-order kinetics and the T-shaped BiVO4 also displayed high photocatalytic performance for metronidazole degradation.

  2. The anti-amoebic activity of some medicinal plants used by AIDS patients in southern Thailand.

    PubMed

    Sawangjaroen, Nongyao; Phongpaichit, S; Subhadhirasakul, S; Visutthi, M; Srisuwan, N; Thammapalerd, N

    2006-05-01

    The anti-amoebic activities of chloroform, methanol and water extracts from 12 Thai medicinal plants (39 extracts) commonly used by AIDS patients in southern Thailand were screened, at a concentration of 1,000 microg/ml, against Entamoeba histolytica strain HTH-56:MUTM and strain HM1:IMSS growing in vitro. The extracts were incubated with 2x10(5) E. histolytica trophozoites/ml of medium at 37 degrees C under anaerobic conditions for 24 h. The cultures were examined with an inverted microscope and scored (1-4) according to the appearance and numbers of the trophozoites. The extracts that caused inhibition were selected and retested using the same conditions but with concentrations that ranged from 31.25 to 1,000 microg/ml using E. histolytica strain HM1:IMSS, and the IC(50) values for each extract were calculated. The chloroform extracts from Alpinia galanga (IC(50) 55.2 microg/ml), Barleria lupulina (IC(50) 78.5 microg/ml), Boesenbergia pandurata (IC(50) 45.8 microg/ml), Piper betle (IC(50) 91.1 microg/ml) and Piper chaba (IC(50) 71.4 microg/ml) and the methanol extract from B. pandurata (IC(50) 57.6 microg/ml) were all classified as "active", i.e. with an IC(50) of less than 100 microg/ml, whereas those from Murraya paniculata (IC(50) 116.5 microg/ml) and Zingiber zerumbet (IC(50) 196.9 microg/ml) were classified as being "moderately active". The IC(50) of a standard drug, metronidazole, was 1.1 microg/ml.

  3. Anti-Helicobacter pylori activities of Chenopodium ambrosioides L. in vitro and in vivo

    PubMed Central

    Ye, Hui; Liu, Yu; Li, Ning; Yu, Jing; Cheng, Hong; Li, Jiang; Zhang, Xue-Zhi

    2015-01-01

    AIM: To investigate the bactericidal effects of Chenopodium ambrosioides L. (CAL) against Helicobacter pylori (H. pylori) both in vitro and in vivo. METHODS: For in vitro experiments, the inhibitory activity of CAL was tested using an agar dilution method; H. pylori strain NCTC11637 was incubated on Columbia blood agar plates containing serial concentrations of CAL. The minimal inhibitory concentration (MIC) was determined by the absence of H. pylori colonies on the agar plate. Time-kill curves were used to evaluate bactericidal activity; the average number of colonies was calculated at 0, 2, 8 and 24 h after liquid incubation with concentrations of CAL at 0.5, 1, and 2 × MIC. For in vivo experiments, H. pylori-infected mice were randomly divided into CAL, triple therapy (lansoprazole, metronidazole, and clarithromycin), blank control, or H. pylori control groups. The eradication ratios were determined by positive findings from rapid urease tests (RUTs) and by histopathology. RESULTS: In vitro, the MIC of CAL against H. pylori was 16 mg/L. The time-kill curves showed a stable and persistent decreasing tendency with increasing CAL concentration, and the intensity of the bactericidal effect was proportional to dose; the 1 and 2 × MIC completely inhibited the growth of H. pylori at 24 h. In vivo, the eradication ratios in the CAL group were 60% (6/10) by RUT and 50% (5/10) by histopathology. Ratios in the triple therapy group were both 70% (7/10), and there was no difference between the CAL and triple therapy groups. Histopathologic evaluation revealed massive bacterial colonization on the surface of gastric mucosa and slight infiltration of mononuclear cells after inoculation with H. pylori, but no obvious inflammation or other pathologic changes in gastric mucosa of mice from CAL and triple therapy groups. CONCLUSION: CAL demonstrates effective bactericidal activity against H. pylori both in vitro and in vivo. PMID:25892867

  4. Get Active

    MedlinePlus

    ... Basics: Health Benefits What are the benefits of physical activity? Physical activity increases your chances of living longer. ... pain Help you feel better about yourself Is physical activity for everyone? Yes! Physical activity is good for ...

  5. First report of anti-Trichomonas vaginalis activity of the medicinal plant Polygala decumbens from the Brazilian semi-arid region, Caatinga.

    PubMed

    Frasson, Amanda Piccoli; dos Santos, Odelta; Duarte, Mariana; da Silva Trentin, Danielle; Giordani, Raquel Brandt; da Silva, Alexandre Gomes; da Silva, Márcia Vanusa; Tasca, Tiana; Macedo, Alexandre José

    2012-06-01

    Trichomonosis, caused by the flagellate protozoan Trichomonas vaginalis, is the most common non-viral sexually transmitted disease worldwide. Actually, the infection treatment is based on 5-nitroimidazole drugs. However, an emergent number of resistant isolates makes important the search for new therapeutic arsenal. In this sense, the investigation of plants and their metabolites is an interesting approach. In the present study, the anti-T. vaginalis activity of 44 aqueous extracts from 23 Caatinga plants used in folk medicine was evaluated. After screening 44 aqueous extracts from 23 distinct plants against two isolates from ATCC and four fresh clinical isolates, only the Polygala decumbens root extract was effective in reducing significantly the trophozoite viability. The MIC value against all isolates tested, including the metronidazole resistant, was 1.56 mg/mL. The kinetic growth assays showed that the extract was able to completely abolish the parasite density in the first hours of incubation, confirmed by microscopy. In summary, this study describes the first report on the activity of P. decumbens from Caatinga against T. vaginalis, being directly related to the popular knowledge and use.

  6. Preclinical testing of the nitroimidazopyran PA-824 for activity against Mycobacterium tuberculosis in a series of in vitro and in vivo models.

    PubMed

    Lenaerts, Anne J; Gruppo, Veronica; Marietta, Karen S; Johnson, Christine M; Driscoll, Diane K; Tompkins, Nicholas M; Rose, Jerry D; Reynolds, Robert C; Orme, Ian M

    2005-06-01

    This study extends earlier reports regarding the in vitro and in vivo efficacies of the nitroimidazopyran PA-824 against Mycobacterium tuberculosis. PA-824 was tested in vitro against a broad panel of multidrug-resistant clinical isolates and was found to be highly active against all isolates (MIC<1 microg/ml). The activity of PA-824 against M. tuberculosis was also assessed grown under conditions of oxygen depletion. PA-824 showed significant activity at 2, 10, and 50 microg/ml, similar to that of metronidazole, in a dose-dependent manner. In a short-course mouse infection model, the efficacy of PA-824 at 50, 100, and 300 mg/kg of body weight formulated in methylcellulose or cyclodextrin/lecithin after nine oral treatments was compared with those of isoniazid, rifampin, and moxifloxacin. PA-824 at 100 mg/kg in cyclodextrin/lecithin was as active as moxifloxacin at 100 mg/kg and isoniazid at 25 mg/kg and was slightly more active than rifampin at 20 mg/kg. Long-term treatment with PA-824 at 100 mg/kg in cyclodextrin/lecithin reduced the bacterial load below 500 CFU in the lungs and spleen. No significant differences in activity between PA-824 and the other single drug treatments tested (isoniazid at 25 mg/kg, rifampin at 10 mg/kg, gatifloxacin at 100 mg/kg, and moxifloxacin at 100 mg/kg) could be observed. In summary, its good activity in in vivo models, as well as its activity against multidrug-resistant M. tuberculosis and against M. tuberculosis isolates in a potentially latent state, makes PA-824 an attractive drug candidate for the therapy of tuberculosis. These data indicate that there is significant potential for effective oral delivery of PA-824 for the treatment of tuberculosis.

  7. Thermosensitive hydrogel for periodontal application: in vitro drug release, antibacterial activity and toxicity evaluation.

    PubMed

    Pakzad, Yousef; Ganji, Fariba

    2016-02-01

    Injectable thermosensitive chitosan hydrogel is an attractive temperature-induced sol-gel solution that is widely used in drug delivery and biomedical applications. In this study, an injectable antimicrobial delivery system for periodontal treatment based on chitosan/gelatin/β-glycerolphosphate solution has been developed. The result of thermal and mechanical evaluations of chitosan/gelatin/β-glycerolphosphate hydrogel showed that adding gelatin to chitosan/β-glycerolphosphate solution significantly decreased gelling time and increased gel strength at 37℃. The antimicrobial agents chosen for release studies were metronidazole with a low molecular weight and vancomycin hydrochloride with a high molecular weight. The initial burst and total in vitro drug release for metronidazole was 13% and 67%, respectively. The initial burst and total drug release for vancomycin hydrochloride was relatively low at 3% and 23%, respectively. The momentary and total percentage of metronidazole accumulated in the phosphate buffer revealed that chitosan/gelatin/β-glycerolphosphate can develop and maintain sustained release of metronidazole in concentrations that are effective for eliminating pathogenic bacteria over time. Cytotoxicity evaluations show that chitosan/gelatin/β-glycerolphosphate thermosensitive hydrogel is a drug carrier with no cytotoxic effects.

  8. Antitrichomonal activity of Peganum harmala alkaloid extract against trichomoniasis in pigeon (Columba livia domestica).

    PubMed

    Tabari, M A; Youssefi, M R; Moghadamnia, A A

    2017-04-12

    1. This study was designed to evaluate the antitrichomonal effects of P. harmala alkaloid extract against T. gallinae, both in vitro and in vivo, as well as comparing it to that of metronidazole, conventional antitrichomonal medication and harmine and harmaline, the two alkaloids present in P. harmala. 2. T. gallinae were collected by the wet mount method from infected free-living pigeons. The in vitro assay was performed using multi-well plates containing test compounds in final concentrations of 5, 10, 15, 20, 30, 50 or 100 μg/ml. The in vivo assay was done on 60 experimentally infected pigeons dosed with metronidazole at 50 mg/kg body weight (BW) or alkaloids at 25 mg/kg BW. 3. The 24 h minimum inhibitory concentration (MIC) of alkaloid extract was 15 µg/ml while that of metronidazole was 50 µg/ml. Harmine and harmaline revealed 24 h MIC of 30 and 100 µg/ml, respectively. Treatment of infected pigeons with alkaloids led to a full recovery after 3 d but with metronidazole total eradication of trophozoites was not achieved. 4. In conclusion, data of the present study suggested P. harmala is a potent natural anti-trichomonal agent, effective against T. gallinae.

  9. Metabolic profile of caecal micro-organisms from rats fed indigestible plant cell-wall components.

    PubMed

    Rowland, I R; Wise, A; Mallett, A K

    1983-02-01

    A fibre-free diet, or the same diet supplemented with 100 g cabbage or carrot cell-wall preparation/kg, was fed to rats for 28 days and the activities of a number of caecal microbial enzymes (azoreductase, aryl nitroreductase, beta-glucosidase, beta-glucuronidase, imidazole nitroreductase and nitrite reductase) were determined in vitro. The plant cell-wall preparations diluted the gut contents and decreased the number of bacteria per gram of caecal contents. Enzyme activities per gram of caecal contents were also decreased, with the exception of beta-glucosidase activity which was significantly increased. These plant cell-wall preparations also increased caecal size, and thereby significantly increased total activity per caecum of microbial azoreductase, aryl nitroreductase, beta-glucosidase and beta-glucuronidase. When bacterial metabolism was expressed per 10(9) bacteria, all enzyme activities were significantly increased in caecal samples from rats fed the plant cell-wall preparations. There was an overall concordance of 0.91 between all the enzymes when expressed per 10(9) bacteria, but of only 0.38 when enzyme activities were expressed per gram of caecal contents.

  10. A Drug Combination Screen Identifies Drugs Active against Amoxicillin-Induced Round Bodies of In Vitro Borrelia burgdorferi Persisters from an FDA Drug Library

    PubMed Central

    Feng, Jie; Shi, Wanliang; Zhang, Shuo; Sullivan, David; Auwaerter, Paul G.; Zhang, Ying

    2016-01-01

    Although currently recommended antibiotics for Lyme disease such as doxycycline or amoxicillin cure the majority of the patients, about 10–20% of patients treated for Lyme disease may experience lingering symptoms including fatigue, pain, or joint and muscle aches. Under experimental stress conditions such as starvation or antibiotic exposure, Borrelia burgdorferi can develop round body forms, which are a type of persister bacteria that appear resistant in vitro to customary first-line antibiotics for Lyme disease. To identify more effective drugs with activity against the round body form of B. burgdorferi, we established a round body persister model induced by exposure to amoxicillin (50 μg/ml) and then screened the Food and Drug Administration drug library consisting of 1581 drug compounds and also 22 drug combinations using the SYBR Green I/propidium iodide viability assay. We identified 23 drug candidates that have higher activity against the round bodies of B. burgdorferi than either amoxicillin or doxycycline. Eleven individual drugs scored better than metronidazole and tinidazole which have been previously described to be active against round bodies. In this amoxicillin-induced round body model, some drug candidates such as daptomycin and clofazimine also displayed enhanced activity which was similar to a previous screen against stationary phase B. burgdorferi persisters not exposure to amoxicillin. Additional candidate drugs active against round bodies identified include artemisinin, ciprofloxacin, nifuroxime, fosfomycin, chlortetracycline, sulfacetamide, sulfamethoxypyridazine and sulfathiozole. Two triple drug combinations had the highest activity against amoxicillin-induced round bodies and stationary phase B. burgdorferi persisters: artemisinin/cefoperazone/doxycycline and sulfachlorpyridazine/daptomycin/doxycycline. These findings confirm and extend previous findings that certain drug combinations have superior activity against B. burgdorferi

  11. Acute podocyte injury is not a stimulus for podocytes to migrate along the glomerular basement membrane in zebrafish larvae

    PubMed Central

    Siegerist, Florian; Blumenthal, Antje; Zhou, Weibin; Endlich, Karlhans; Endlich, Nicole

    2017-01-01

    Podocytes have a unique 3D structure of major and interdigitating foot processes which is the prerequisite for renal blood filtration. Loss of podocytes leads to chronic kidney disease ending in end stage renal disease. Until now, the question if podocytes can be replaced by immigration of cells along the glomerular basement membrane (GBM) is under debate. We recently showed that in contrast to former theories, podocytes are stationary in the zebrafish pronephros and neither migrate nor change their branching pattern of major processes over 23 hours. However, it was still unclear whether podocytes are able to migrate during acute injury. To investigate this, we applied the nitroreductase/metronidazole zebrafish model of podocyte injury to in vivo two-photon microscopy. The application of metronidazole led to retractions of major processes associated with a reduced expression of podocyte-specific proteins and a formation of subpodocyte pseudocyst. Electron microscopy showed that broad areas of the capillaries became denuded. By 4D in vivo observation of single podocytes, we could show that the remaining podocytes did not walk along GBM during 24 h. This in vivo study reveals that podocytes are very stationary cells making regenerative processes by podocyte walking along the GBM very unlikely. PMID:28252672

  12. Comparative Mutagenicity of Urinary Metabolites of Nitropolycylic Aromatic Hydrocarbons 1-Nitropyrene, 2-Nitrofluoranthene, and 3- Nitrofluoranthene

    DTIC Science & Technology

    1991-01-01

    metabolite may then be transported to the intestines. Intestinal flora may reduce the metabolite while B-Glucuronidase- and Sulfatase - containing hacteria may...metabolism (Ball & King, 85). Several bacterial strains are capable of these pathways, but unfortunately multiple strains can not easily be used...frameshift mutation is required to reset the gene frame for proper function. Nitroreductase is a key metabolic activity of TA98 as nonreductase deficient

  13. Activation detector

    DOEpatents

    Bell, Zane William [Oak Ridge, TN; Boatner, Lynn Allen [Oak Ridge, TN

    2009-12-08

    A method of detecting an activator, the method including impinging with an activator a receptor material lacking a photoluminescent material and generating a by-product of a radioactive decay due to the activator impinging the reeptor material. The method further including, generating light from the by-product via the Cherenkov effect and identifying a characteristic of the activator based on the light.

  14. In vitro studies on the sensitivity of local Entamoeba histolytica to anti-amoebic drugs.

    PubMed

    Chintana, T; Sucharit, P; Mahakittikun, V; Siripanth, C; Suphadtanaphongs, W

    1986-12-01

    The in vitro activity of drugs, namely dehydroemetine, ornidazole, metronidazole and tinidazole were determined against the locally isolated strains of E. histolytica in Thailand. The test was performed in liquid monophasic medium, i.e. liver marmite serum medium. In all, locally isolated strains from thirty hosts studied, the minimal inhibitory concentration (MIC) for dehydroemetine ranged from 0.125 to 1 microgram/ml, ornidazole ranged from 0.0625 to 0.25 microgram/ml, metronidazole ranged from 0.0625 to 0.125 microgram/ml, and tinidazole ranged from 0.0625 microgram/ml to 0.25 microgram/ml. The MIC of dehydroemetine was significantly different from ornidazole, metronidazole and tinidazole. Metronidazole was superior to that of dehydroemetine but was not significantly different among ornidazole, metronidazole and tinidazole.

  15. Persistent and recurrent Trichomonas vaginalis infections: epidemiology, treatment and management considerations.

    PubMed

    Seña, Arlene C; Bachmann, Laura H; Hobbs, Marcia M

    2014-06-01

    Trichomonas vaginalis (TV) is a common sexually transmitted infection that can cause vaginitis, cervicitis and urethritis. Persistent and recurrent TV infections are frequent in women, potentially due to the lack of routine screening recommendations for this pathogen, the chronic nature of some infections, and drug resistance. Metronidazole and tinidazole are two oral drugs that are effective against trichomoniasis. There are few alternative treatment options for persons with a metronidazole allergy or treatment failure. Most TV isolates from women with treatment failures that have been analyzed for susceptibility testing in the United States have exhibited low-level metronidazole resistance, supporting the initial use of tinidazole for patients who fail metronidazole therapy. Several non-nitroimidazole drugs and other agents have demonstrated acceptable in vitro activity or cure rates in case reports for metronidazole-resistant trichomoniasis; however, clinical trials are imperative to evaluate their efficacy as alternative therapeutic regimens for this highly prevalent infection.

  16. Efficacy of two plant extracts against vaginal trichomoniasis.

    PubMed

    El-Sherbini, Gehad T M; El Gozamy, Bothina R; Abdel-Hady, Nevein M; Morsy, Tosson A

    2009-04-01

    Trichomoniasis vaginalis is now an important worldwide health problem. Metronidazole has so far been used in treatment, but the metronidazole-resistant strains and unpleasant adverse effects have been developed. Treatment of patients with metronidazole refractory vaginal trichomoniasis constitutes a major therapeutic challenge and treatment options are extremely limited. In the present study, 33 metronidazole-resistant T. vaginalis females were treated with a combined course of metronidazole and tinidazole. Those still resistant to the combined treatment were given Commiphora molmol (Myrrh) as two capsules for six to eight successive days on an empty stomach two hours before breakfast. Also, natural plant extract purified from (Roman) was in-vitro investigated for its efficacy against T. vaginalis on fresh Diamond media. The anti-trichomoniasis vaginalis activity of both P. granatum (in-vitro) and C. molmol (in-vivo) extracts gave promising results.

  17. Synergistic effect of p-n heterojunction, supporting and zeolite nanoparticles in enhanced photocatalytic activity of NiO and SnO2.

    PubMed

    Derikvandi, Hadis; Nezamzadeh-Ejhieh, Alireza

    2017-03-15

    Increased photocatalytic activity of NiO and SnO2 was achieved by coupling and supporting of them onto clinoptilolite nanoparticles (NC) via calcination of Ni(II)-Sn(IV) - exchanged NC in photocatalytic degradation of metronidazole (MZ) aqueous solution. XRD, XRF, FTIR, SEM, X-ray mapping, DRS, TEM, BET Cyclic voltammetry and electrochemical impedance spectroscopy techniques (EIS) were used for characterization of samples. Red shift occurred in bang gap energies of the coupled semiconductors with respect to monocomponent one. This p-n hetero-junction forms a depletion layer in the semiconductors interface with negative and positive charges, causing considerable enhancement in the photocatalytic activity. The calcined catalyst at 600°C for 4h showed the best photocatalytic activity and charge transfer efficiency (in EIS results). The mole ratio of SnO2/NiO affects the degradation activity of the catalysts and the best activity were was obtained for the NiO1.1-SnO2(6.7)/NC (NS5-NC) catalyst at pH 3, 1.2gL(-)(1) of the catalyst and 2mgL(-)(1) of MZ. SnO2 played electron sink role and the photogenerated electrons migrate from more negative Cb-NiO (E=-3.0V) to Cb-SnO2 (E=-0.3V vs SHE). Initial pH of MZ solution was changed from 6.20 to 4.73 during 180min that confirms formation of Oxalic acid and Maleic acid.

  18. Controlled synthesis of T-shaped BiVO{sub 4} and enhanced visible light responsive photocatalytic activity

    SciTech Connect

    Dong, Shuying; Yu, Chongfei; Li, Yukun; Li, Yihui; Sun, Jianhui; Geng, Xiaofei

    2014-03-15

    A novel T-shaped BiVO{sub 4} microcrystal photocatalyst was successfully synthesized by the hydrothermal method with the aid of a structure-directing surfactant SDBS in the present study. Having received well characterization with the aid of various techniques and the results showed that the SDBS greatly changed the microstructure of BiVO{sub 4}, which had a unique T shape and belonged to the monoclinic family. The fast exchange dynamics between the surfactants bound to the Bi{sup 3+} seed surface and the free VO{sub 3}{sup −} in the solution significantly increase the rate of heterogeneous nucleation. In addition, the photocatalytic activity of the prepared T-shaped BiVO{sub 4} was evaluated by the degradation of Methylene Blue solution under visible light irradiation, 17% and 47% higher decolorization rates than the commercial P25 and BiVO{sub 4} synthesized without SDBS, respectively. Meanwhile, it has been found that the degradation kinetics of MB fitted the pseudo-first-order kinetics and the T-shaped BiVO{sub 4} also displayed high photocatalytic performance for metronidazole degradation. -- Graphical abstract: H{sub 2}O{sub 2} molecules function as electron trapping reagent to react with e{sup −} to enhance the photocatalytic degradation efficiency of MB in the BiVO{sub 4}/H{sub 2}O{sub 2} system under visible light irradiation. Highlights: • T-shaped BiVO{sub 4} was synthesized using SDBS as a structure-directing surfactant. • SDBS greatly changed the microstructure of BiVO{sub 4}. • The T-shaped BiVO{sub 4} had a better visible-light photocatalytic activity. • Degradation kinetics of MB by BiVO{sub 4} fitted the pseudo-first-order kinetics.

  19. Biodegradation of pendimethalin by Bacillus subtilis Y3.

    PubMed

    Ni, Haiyan; Yao, Li; Li, Na; Cao, Qin; Dai, Chen; Zhang, Jun; He, Qin; He, Jian

    2016-03-01

    A bacterium strain Y3, capable of efficiently degrading pendimethalin, was isolated from activated sludge and identified as Bacillus subtilis according to its phenotypic features and 16S rRNA phylogenetic analysis. This strain could grow on pendimethalin as a sole carbon source and degrade 99.5% of 100mg/L pendimethalin within 2.5days in batch liquid culture, demonstrating a greater efficiency than any other reported strains. Three metabolic products, 6-aminopendimethalin, 5-amino-2-methyl-3-nitroso-4-(pentan-3-ylamino) benzoic acid, and 8-amino-2-ethyl-5-(hydroxymethyl)-1,2-dihydroquinoxaline-6-carboxylic acid, were identified by HPLC-MS/MS, and a new microbial degradation pathway was proposed. A nitroreductase catalyzing nitroreduction of pendimethalin to 6-aminopendimethalin was detected in the cell lysate of strain Y3. The cofactor was nicotinamide adenine dinucleotide phosphate (NADPH) or more preferably nicotinamide adenine dinucleotide (NADH). The optimal temperature and pH for the nitroreductase were 30°C and 7.5, respectively. Hg(2+), Ni(2+), Pb(2+), Co(2+), Mn(2+) Cu(2+), Ag(+), and EDTA severely inhibited the nitroreductase activity, whereas Fe(2+), Mg(2+), and Ca(2+) enhanced it. This study provides an efficient pendimethalin-degrading microorganism and broadens the knowledge of the microbial degradation pathway of pendimethalin.

  20. Catalyst activator

    DOEpatents

    McAdon, Mark H.; Nickias, Peter N.; Marks, Tobin J.; Schwartz, David J.

    2001-01-01

    A catalyst activator particularly adapted for use in the activation of metal complexes of metals of Group 3-10 for polymerization of ethylenically unsaturated polymerizable monomers, especially olefins, comprising two Group 13 metal or metalloid atoms and a ligand structure including at least one bridging group connecting ligands on the two Group 13 metal or metalloid atoms.

  1. Outdoor Activities.

    ERIC Educational Resources Information Center

    Minneapolis Independent School District 275, Minn.

    Twenty-four activities suitable for outdoor use by elementary school children are outlined. Activities designed to make children aware of their environment include soil painting, burr collecting, insect and pond water collecting, studies of insect galls and field mice, succession studies, and a model of natural selection using dyed toothpicks. A…

  2. Physical activity

    MedlinePlus

    ... activity -- which includes an active lifestyle and routine exercise -- plus eating well, is the best way to stay healthy. ... goal. Your goal might be to: Manage a health condition Reduce stress ... other benefits, such as: Better control of your weight and ...

  3. Astronomy Activities.

    ERIC Educational Resources Information Center

    Greenstone, Sid

    This document consists of activities and references for teaching astronomy. The activities (which include objectives, list of materials needed, and procedures) focus on: observing the Big Dipper and locating the North Star; examining the Big Dipper's stars; making and using an astrolabe; examining retograde motion of Mars; measuring the Sun's…

  4. Identification of candidate agents active against N. ceranae infection in honey bees: establishment of a medium throughput screening assay based on N. ceranae infected cultured cells.

    PubMed

    Gisder, Sebastian; Genersch, Elke

    2015-01-01

    Many flowering plants in both natural ecosytems and agriculture are dependent on insect pollination for fruit set and seed production. Managed honey bees (Apis mellifera) and wild bees are key pollinators providing this indispensable eco- and agrosystem service. Like all other organisms, bees are attacked by numerous pathogens and parasites. Nosema apis is a honey bee pathogenic microsporidium which is widely distributed in honey bee populations without causing much harm. Its congener Nosema ceranae was originally described as pathogen of the Eastern honey bee (Apis cerana) but jumped host from A. cerana to A. mellifera about 20 years ago and spilled over from A. mellifera to Bombus spp. quite recently. N. ceranae is now considered a deadly emerging parasite of both Western honey bees and bumblebees. Hence, novel and sustainable treatment strategies against N. ceranae are urgently needed to protect honey and wild bees. We here present the development of an in vitro medium throughput screening assay for the identification of candidate agents active against N. ceranae infections. This novel assay is based on our recently developed cell culture model for N. ceranae and coupled with an RT-PCR-ELISA protocol for quantification of N. ceranae in infected cells. The assay has been adapted to the 96-well microplate format to allow automated analysis. Several substances with known (fumagillin) or presumed (surfactin) or no (paromomycin) activity against N. ceranae were tested as well as substances for which no data concerning N. ceranae inhibition existed. While fumagillin and two nitroimidazoles (metronidazole, tinidazole) totally inhibited N. ceranae proliferation, all other test substances were inactive. In summary, the assay proved suitable for substance screening and demonstrated the activity of two synthetic antibiotics against N. ceranae.

  5. Identification of Candidate Agents Active against N. ceranae Infection in Honey Bees: Establishment of a Medium Throughput Screening Assay Based on N. ceranae Infected Cultured Cells

    PubMed Central

    Gisder, Sebastian; Genersch, Elke

    2015-01-01

    Many flowering plants in both natural ecosytems and agriculture are dependent on insect pollination for fruit set and seed production. Managed honey bees (Apis mellifera) and wild bees are key pollinators providing this indispensable eco- and agrosystem service. Like all other organisms, bees are attacked by numerous pathogens and parasites. Nosema apis is a honey bee pathogenic microsporidium which is widely distributed in honey bee populations without causing much harm. Its congener Nosema ceranae was originally described as pathogen of the Eastern honey bee (Apis cerana) but jumped host from A. cerana to A. mellifera about 20 years ago and spilled over from A. mellifera to Bombus spp. quite recently. N. ceranae is now considered a deadly emerging parasite of both Western honey bees and bumblebees. Hence, novel and sustainable treatment strategies against N. ceranae are urgently needed to protect honey and wild bees. We here present the development of an in vitro medium throughput screening assay for the identification of candidate agents active against N. ceranae infections. This novel assay is based on our recently developed cell culture model for N. ceranae and coupled with an RT-PCR-ELISA protocol for quantification of N. ceranae in infected cells. The assay has been adapted to the 96-well microplate format to allow automated analysis. Several substances with known (fumagillin) or presumed (surfactin) or no (paromomycin) activity against N. ceranae were tested as well as substances for which no data concerning N. ceranae inhibition existed. While fumagillin and two nitroimidazoles (metronidazole, tinidazole) totally inhibited N. ceranae proliferation, all other test substances were inactive. In summary, the assay proved suitable for substance screening and demonstrated the activity of two synthetic antibiotics against N. ceranae. PMID:25658121

  6. In Vitro and In Vivo Antibacterial Activities of Patchouli Alcohol, a Natural-occurring Tricyclic Sesquiterpene against Helicobacter pylori Infection.

    PubMed

    Xu, Y F; Lian, D W; Chen, Y Q; Cai, Y F; Zheng, Y F; Fan, P L; Ren, W K; Fu, L J; Li, Y C; Xie, J H; Cao, H Y; Tan, B; Su, Z R; Huang, P

    2017-03-20

    This study further evaluated the in vitro and in vivo anti-Helicobacter pylori activity and potential underlying mechanism of patchouli alcohol (PA), a tricyclic sesquiterpene. In in vitro assay, the capacities of PA to inhibit and kill H. pylori were tested on three standard strains at different pH values and 12 clinical isolates. The effects of PA on H. pylori adhesion (and its alpA, alpB and babA genes), motility (and its flaA and flaB genes), ultrastructure and flagellation were investigated. Moreover, the H. pylori resistance and post-antibiotic effect (PAE) of PA were determined. Furthermore, the in vivo effects of PA on H. pylori eradication and gastritis were examined. Results showed that MICs of PA against three standard strains (pH 5.3-9) and twelve clinical isolates were 25-75 and 12.5-50 μg/ml, respectively. The killing kinetics of PA were time- and concentration- dependent, and its MBCs were 25-75 μg/ml. Besides, H. pylori adhesion, motility, ultrastructure and flagellation were significantly suppressed. PA also remarkably inhibited the expression of adhesion genes (alpA and alpB), and motility genes (flaA and flaB). Furthermore, PA treatment caused a long PAE and less bacterial resistance as compared with clarithromycin and metronidazole. The in vivo study showed that PA can effectively eradicate H. pylori, inhibit gastritis, and suppress the expression of inflammatory mediators (Cox-2, Il-1β, Tnf-α and Inos). In conclusion, PA can efficiently kill H. pylori, interfere with its infection process and attenuate gastritis with less bacterial resistance, making it a potential candidate for new drug development.

  7. Cefotetan: a second-generation cephalosporin active against anaerobic bacteria. Committee on Antimicrobial Agents, Canadian Infectious Disease Society.

    PubMed Central

    Gribble, M J

    1994-01-01

    OBJECTIVE: To offer guidelines for the use of cefotetan, a cephamycin antibiotic, in order to minimize its overprescription. OPTIONS: Clinical practice options considered were treatment of infections with the use of second- and third-generation cephalosporins, carbapenems such as imipenem as well as combination regimens of agents active against anaerobic bacteria, such as metronidazole or clindamycin with an aminoglycoside. OUTCOMES: In order of importance: efficacy, side effects and cost. EVIDENCE: A MEDLINE search of articles published between January 1982 and December 1993. In-vitro and pharmacokinetic studies published in recognized peer-reviewed journals that used recognized standard methods with appropriate controls were reviewed. For results of clinical trials, the reviewers emphasized randomized double-blind trials with appropriate controls. VALUES: The Antimicrobial Agents Committee of the Canadian Infectious Disease Society (CIDS) and a recognized expert (M.J.G.) recommended use of cefotetan to prevent and treat infections against which it has proved effective in randomized controlled trials. BENEFITS, HARMS AND COSTS: These guidelines should lead to less inappropriate prescribing of cefotetan, with its attendant costs and risk of development of resistant bacteria. RECOMMENDATIONS: Cefotetan could be considered an alternative single agent for prophylaxis of infection in patients undergoing elective bowel surgery. It may be used to treat patients with acute pelvic inflammatory disease and endometritis. VALIDATION: This article was prepared, reviewed and revised by the Committee on Antimicrobial Agents of the CIDS. It was then reviewed by the Council of the CIDS, and any further necessary revisions were made by the chairman of the committee. PMID:8069799

  8. Activated Charcoal

    MedlinePlus

    ... is used to treat poisonings, reduce intestinal gas (flatulence), lower cholesterol levels, prevent hangover, and treat bile ... lower cholesterol levels in the blood. Decreasing gas (flatulence). Some studies show that activated charcoal is effective ...

  9. Activity Theory.

    ERIC Educational Resources Information Center

    Koschmann, Timothy; Roschelle, Jeremy; Nardi, Bonnie A.

    1998-01-01

    Includes three articles that discuss activity theory, based on "Context and Consciousness." Topics include human-computer interaction; computer interfaces; hierarchical structuring; mediation; contradictions and development; failure analysis; and designing educational technology. (LRW)

  10. Plant metacaspase activation and activity.

    PubMed

    Minina, Elena A; Stael, Simon; Van Breusegem, Frank; Bozhkov, Peter V

    2014-01-01

    Metacaspases are essential for cell death regulation in plants. Further understanding of biochemistry of metacaspases and their molecular function in plant biology requires a set of robust methods for detection of metacaspase activation and quantitative analysis of corresponding proteolytic activity. Here we describe methods for purification of recombinant metacaspases, measurement of enzymatic activity of recombinant and endogenous metacaspases in vitro and in cell lysates, respectively, and finally detection of metacaspase activation in vivo. Additionally, an in vitro metacaspase protein substrate cleavage assay based on the cell-free production of substrate protein followed by proteolysis with recombinant metacaspase is presented. These methods have been originally developed for type II metacaspases from Arabidopsis and Norway spruce (Picea abies), but they can be used as templates for type I metacaspases, as well as for type II metacaspases from other species.

  11. Green Synthesis of Silver Nanoparticles through Reduction with Solanum xanthocarpum L. Berry Extract: Characterization, Antimicrobial and Urease Inhibitory Activities against Helicobacter pylori

    PubMed Central

    Amin, Muhammad; Anwar, Farooq; Janjua, Muhammad Ramzan Saeed Ashraf; Iqbal, Muhammad Awais; Rashid, Umer

    2012-01-01

    A green synthesis route for the production of silver nanoparticles using methanol extract from Solanum xanthocarpum berry (SXE) is reported in the present investigation. Silver nanoparticles (AgNps), having a surface plasmon resonance (SPR) band centered at 406 nm, were synthesized by reacting SXE (as capping as well as reducing agent) with AgNO3 during a 25 min process at 45 °C. The synthesized AgNps were characterized using UV–Visible spectrophotometry, powdered X-ray diffraction, and transmission electron microscopy (TEM). The results showed that the time of reaction, temperature and volume ratio of SXE to AgNO3 could accelerate the reduction rate of Ag+ and affect the AgNps size and shape. The nanoparticles were found to be about 10 nm in size, mono-dispersed in nature, and spherical in shape. In vitro anti-Helicobacter pylori activity of synthesized AgNps was tested against 34 clinical isolates and two reference strains of Helicobacter pylori by the agar dilution method and compared with AgNO3 and four standard drugs, namely amoxicillin (AMX), clarithromycin (CLA), metronidazole (MNZ) and tetracycline (TET), being used in anti-H. pylori therapy. Typical AgNps sample (S1) effectively inhibited the growth of H. pylori, indicating a stronger anti-H. pylori activity than that of AgNO3 or MNZ, being almost equally potent to TET and less potent than AMX and CLA. AgNps under study were found to be equally efficient against the antibiotic-resistant and antibiotic-susceptible strains of H. pylori. Besides, in the H. pylori urease inhibitory assay, S1 also exhibited a significant inhibition. Lineweaver-Burk plots revealed that the mechanism of inhibition was noncompetitive. PMID:22949839

  12. Active colloids

    NASA Astrophysics Data System (ADS)

    Aranson, Igor S.

    2013-01-01

    A colloidal suspension is a heterogeneous fluid containing solid microscopic particles. Colloids play an important role in our everyday life, from food and pharmaceutical industries to medicine and nanotechnology. It is useful to distinguish two major classes of colloidal suspensions: equilibrium and active, i.e., maintained out of thermodynamic equilibrium by external electric or magnetic fields, light, chemical reactions, or hydrodynamic shear flow. While the properties of equilibrium colloidal suspensions are fairly well understood, active colloids pose a formidable challenge, and the research is in its early exploratory stage. One of the most remarkable properties of active colloids is the possibility of dynamic self-assembly, a natural tendency of simple building blocks to organize into complex functional architectures. Examples range from tunable, self-healing colloidal crystals and membranes to self-assembled microswimmers and robots. Active colloidal suspensions may exhibit material properties not present in their equilibrium counterparts, e.g., reduced viscosity and enhanced self-diffusivity, etc. This study surveys the most recent developments in the physics of active colloids, both in synthetic and living systems, with the aim of elucidation of the fundamental physical mechanisms governing self-assembly and collective behavior.

  13. INDUCTION OF ALBENDAZOLE RESISTANCE IN GIARDIA LAMBLIA

    EPA Science Inventory

    Previous studies have shown that Giardia lamblia resistance to metronidazole can be induced in the laboratory, and treatment failures with this drug have also been documented. As replacement theraples, anthelmintic benzimidazoles have antigiardial activity with few clinical side ...

  14. Active microwaves

    NASA Technical Reports Server (NTRS)

    Evans, D.; Vidal-Madjar, D.

    1994-01-01

    Research on the use of active microwaves in remote sensing, presented during plenary and poster sessions, is summarized. The main highlights are: calibration techniques are well understood; innovative modeling approaches have been developed which increase active microwave applications (segmentation prior to model inversion, use of ERS-1 scatterometer, simulations); polarization angle and frequency diversity improves characterization of ice sheets, vegetation, and determination of soil moisture (X band sensor study); SAR (Synthetic Aperture Radar) interferometry potential is emerging; use of multiple sensors/extended spectral signatures is important (increase emphasis).

  15. Activated Sludge.

    ERIC Educational Resources Information Center

    Saunders, F. Michael

    1978-01-01

    Presents the 1978 literature review of wastewater treatment. This review covers: (1) activated sludge process; (2) process control; (3) oxygen uptake and transfer; (4) phosphorus removal; (5) nitrification; (6) industrial wastewater; and (7) aerobic digestion. A list of 136 references is also presented. (HM)

  16. Activities: Spirolaterals.

    ERIC Educational Resources Information Center

    Brannan, Richard; McFadden, Scott

    1981-01-01

    A set of activities designed to help students discover properties about order-3 spirolaterals on square grid paper is presented. The materials are prepared on worksheets designed for easy duplication. The lessons can lead to investigations involving spirolaterals of many other orders and shapes. (MP)

  17. Leaf Activities.

    ERIC Educational Resources Information Center

    Mingie, Walter

    Leaf activities can provide a means of using basic concepts of outdoor education to learn in elementary level subject areas. Equipment needed includes leaves, a clipboard with paper, and a pencil. A bag of leaves may be brought into the classroom if weather conditions or time do not permit going outdoors. Each student should pick a leaf, examine…

  18. Learning Activities.

    ERIC Educational Resources Information Center

    Tipton, Tom, Ed.

    1983-01-01

    Presents a flow chart for naming inorganic compounds. Although it is not necessary for students to memorize rules, preliminary skills needed before using the chart are outlined. Also presents an activity in which the mass of an imaginary atom is determined using lead shot, Petri dishes, and a platform balance. (JN)

  19. Activity report

    SciTech Connect

    Yu, S W

    2008-08-11

    This report is aimed to show the author's activities to support the LDRD. The title is 'Investigation of the Double-C Behavior in the Pu-Ga Time-Temperature-Transformation Diagram' The sections are: (1) Sample Holder Test; (2) Calculation of x-ray diffraction patterns; (3) Literature search and preparing publications; (4) Tasks Required for APS Experiments; and (5) Communications.

  20. Drug Development and Conservation of Biodiversity in West and Central Africa

    DTIC Science & Technology

    2003-05-01

    trichomonads ( Trichomonas vaginalis , Tritrichomonas foetus). In the trypanosome growth screen, 58 WRAIR extracts and 8 AP#2 extracts were tested. Eight WRAIR...extracts were tested vs metronidazole-resistant and -sensitive strains of T. vaginalis and another 31 were studied in a T. foetus screen. Of 58 WRAIR...metronidazole-resistant T. vaginalis ; 4 of 31 extracts were similarly active for T. foetus. For trypanosomes, plant genera yielding active extracts included

  1. Antimicrobial Activity.

    PubMed

    2016-01-01

    Natural products of higher plants may possess a new source of antimicrobial agents with possibly novel mechanisms of action. They are effective in the treatment of infectious diseases while simultaneously mitigating many of the side effects that are often associated with conventional antimicrobials. A method using scanning electron microscope (SEM) to study the morphology of the bacterial and fungal microbes and thus determining antimicrobial activity is presented in the chapter.

  2. Comprehensive study on enhanced photocatalytic activity of heterojunction ZnS-NiS/zeolite nanoparticles: Experimental design based on response surface methodology (RSM), impedance spectroscopy and GC-MASS studies.

    PubMed

    Derikvandi, Hadis; Nezamzadeh-Ejhieh, Alireza

    2017-03-15

    In the present work, coupled and supported NiS and ZnS onto the mechanically prepared clinoptilolite nanoparticles (NC) was prepared and characterized by XRD, FTIR, SEM-EDX, X-ray mapping, DRS, BET, cyclic voltammetry (CV) and electrochemical impedance spectroscopy (EIS) techniques. The obtained catalysts were used in photodegradation of metronidazole (MZ). The mole ratio of NiS/ZnS affects the degradation activity of the obtained catalysts so the best activity was obtained for the NZ4-NC (NiS1.0-ZnS5.2/NC, containing 1.0 and 5.2W% of NiS and ZnS, respectively and mole ratio of ZnS/NiS about 4) catalyst. The simultaneous effects of the experimental parameters were studied using central composite design combined with response surface methodology (RSM). Results of CV and EIS have good agreement with photodegradation results, so the coupled NiS-ZnS-NC system with significant enhancement in charge transfer with respect to the monocomponent systems showed the best photodegradation activity. The best degradation extent of MZ was obtained at a run including pH 2, catalyst dose of 3gL(-1), 4mgL(-1) of MZ at irradiation time of 150min. The high correlation coefficient (R(2)=0.9883) for the second-order polynomial model, showed that the data predicted using RSM were in good agreement with the experimental results. Change of initial pH of MZ solution from 5.5 to 4.1 during 150min, confirms formation of acidic degradation intermediates.

  3. In Vitro Activity of 2-methoxy-1,4-naphthoquinone and Stigmasta-7,22-diene-3β-ol from Impatiens balsamina L. against Multiple Antibiotic-Resistant Helicobacter pylori

    PubMed Central

    Wang, Yuan-Chuen; Li, Wan-Yu; Wu, Deng-Chyang; Wang, Jeh-Jeng; Wu, Cheng-Hsun; Liao, Jyun-Ji; Lin, Cheng-Kun

    2011-01-01

    Infection with Helicobacter pylori is strongly associated with gastric cancer and gastric adenocarcinoma. WHO classified H. pylori as a group 1 carcinogen in 1994. Impatiens balsamina L. has been used as indigenous medicine in Asia for the treatment of rheumatism, fractures and fingernail inflammation. In this study, we isolated anti-H. pylori compounds from this plant and investigated their anti- and bactericidal activity. Compounds of 2-methoxy-1,4-naphthoquinone (MeONQ) and stigmasta-7,22-diene-3β-ol (spinasterol) were isolated from the pods and roots/stems/leaves of I. balsamina L., respectively. The minimum inhibitory concentrations (MICs) and minimum bactericidal concentrations (MBCs) for MeONQ were in the ranges of 0.156–0.625 and 0.313–0.625 μg mL−1, respectively, and in the ranges of 20–80 μg mL−1 both of MICs and MBCs for spinasterol against antibiotic (clarithromycin, metronidazole and levofloxacin) resistant H. pylori. Notably, the activity of MeONQ was equivalent to that of amoxicillin (AMX). The bactericidal H. pylori action of MeONQ was dose-dependent. Furthermore, the activity of MeONQ was not influenced by the environmental pH values (4–8) and demonstrated good thermal (121°C for 15 min) stability. MeONQ abounds in the I. balsamina L. pod at the level of 4.39% (w/w db). In conclusion, MeONQ exhibits strong potential to be developed as a candidate agent for the eradication of H. pylori infection. PMID:19773391

  4. Influence of First-Line Antibiotics on the Antibacterial Activities of Acetone Stem Bark Extract of Acacia mearnsii De Wild. against Drug-Resistant Bacterial Isolates

    PubMed Central

    Olajuyigbe, Olufunmiso O.; Coopoosamy, Roger M.

    2014-01-01

    Background. This study was aimed at evaluating the antibacterial activity of the acetone extract of A. mearnsii and its interactions with antibiotics against some resistant bacterial strains. Methods. The antibacterial susceptibility testing was determined by agar diffusion and macrobroth dilution methods while the checkerboard method was used for the determination of synergy between the antibiotics and the extract. Results. The results showed that the susceptibility of the different bacterial isolates was concentration dependent for the extract and the different antibiotics. With the exception of S. marcescens, the inhibition zones of the extract produced by 20 mg/mL ranged between 18 and 32 mm. While metronidazole did not inhibit any of the bacterial isolates, all the antibiotics and their combinations, except for ciprofloxacin and its combination, did not inhibit Enterococcus faecalis. The antibacterial combinations were more of being antagonistic than of being synergistic in the agar diffusion assay. From the macrobroth dilution, the extract and the antibiotics exerted a varied degree of inhibitory effect on the test organisms. The MIC values of the acetone extract which are in mg/mL are lower than those of the different antibiotics which are in μg/mL. From the checkerboard assay, the antibacterial combinations showed varied degrees of interactions including synergism, additive, indifference, and antagonism interactions. While antagonistic and additive interactions were 14.44%, indifference interaction was 22.22% and synergistic interaction was 37.78% of the antibacterial combinations against the test isolates. While the additivity/indifference interactions indicated no interactions, the antagonistic interaction may be considered as a negative interaction that could result in toxicity and suboptimal bioactivity. Conclusion. The synergistic effects of the herbal-drug combinations may be harnessed for the discovery and development of more rational evidence

  5. Analgesic Activity.

    PubMed

    2016-01-01

    Analgesics are agents which selectively relieve pain by acting in the CNS and peripheral pain mediators without changing consciousness. Analgesics may be narcotic or non-narcotic. The study of pain in animals raises ethical, philosophical, and technical problems. Both peripheral and central pain models are included to make the test more evident for the analgesic property of the plant. This chapter highlights methods such as hot plate and formalin and acetic acid-induced pain models to check the analgesic activity of medicinal plants.

  6. Active packaging with antifungal activities.

    PubMed

    Nguyen Van Long, N; Joly, Catherine; Dantigny, Philippe

    2016-03-02

    There have been many reviews concerned with antimicrobial food packaging, and with the use of antifungal compounds, but none provided an exhaustive picture of the applications of active packaging to control fungal spoilage. Very recently, many studies have been done in these fields, therefore it is timely to review this topic. This article examines the effects of essential oils, preservatives, natural products, chemical fungicides, nanoparticles coated to different films, and chitosan in vitro on the growth of moulds, but also in vivo on the mould free shelf-life of bread, cheese, and fresh fruits and vegetables. A short section is also dedicated to yeasts. All the applications are described from a microbiological point of view, and these were sorted depending on the name of the species. Methods and results obtained are discussed. Essential oils and preservatives were ranked by increased efficacy on mould growth. For all the tested molecules, Penicillium species were shown more sensitive than Aspergillus species. However, comparison between the results was difficult because it appeared that the efficiency of active packaging depended greatly on the environmental factors of food such as water activity, pH, temperature, NaCl concentration, the nature, the size, and the mode of application of the films, in addition to the fact that the amount of released antifungal compounds was not constant with time.

  7. Active tectonics

    SciTech Connect

    Not Available

    1986-01-01

    This study is part of a series of Studies in Geophysics that have been undertaken for the Geophysics Research Forum by the Geophysics Study Committee. One purpose of each study is to provide assessments from the scientific community to aid policymakers in decisions on societal problems that involve geophysics. An important part of such assessments is an evaluation of the adequacy of current geophysical knowledge and the appropriateness of current research programs as a source of information required for those decisions. The study addresses our current scientific understanding of active tectonics --- particularly the patterns and rates of ongoing tectonic processes. Many of these processes cannot be described reasonably using the limited instrumental or historical records; however, most can be described adequately for practical purposes using the geologic record of the past 500,000 years. A program of fundamental research focusing especially on Quaternary tectonic geology and geomorphology, paleoseismology, neotectonics, and geodesy is recommended to better understand ongoing, active tectonic processes. This volume contains 16 papers. Individual papers are indexed separately on the Energy Database.

  8. IASS Activity

    NASA Astrophysics Data System (ADS)

    Hojaev, Alisher S.; Ibragimova, Elvira M.

    2015-08-01

    It’s well known, astronomy in Uzbekistan has ancient roots and traditions (e.g., Mirzo Ulugh Beg, Abū al-Rayhān al-Bīrūnī, Abū ‘Abdallāh al-Khwārizmī) and astronomical heritage carefully preserved. Nowadays uzbek astronomers play a key role in scientific research but also in OAD and Decadal Plan activity in the Central Asia region. International Aerospace School (IASS) is an amazing and wonderful event held annually about 30 years. IASS is unique project in the region, and at the beginning we spent the Summer and Winter Schools. At present in the summer camp we gather about 50 teenage and undergraduate students over the country and abroad (France, Malaysia, Turkey, Azerbaijan, Pakistan, Russia, etc.). They are selected on the basis of tests of astronomy and space issues. During two weeks of IASS camp the invited scientists, cosmonauts and astronauts as well as other specialists give lectures and engage in practical exercises with IASS students in astronomy, including daily observations of the Sun and night sky observations with meniscus telescope, space research and exploration, aerospace modelling, preparation and presentation of original projects. This is important that IASS gives not theoretical grounds only but also practically train the students and the hands-on training is the major aims of IASS. Lectures and practice in the field of astronomy carried out with the direct involvement and generous assistance of Uranoscope Association (Paris, France). The current 26-th IASS is planned to held in July 2015.

  9. Physical Activity (Exercise)

    MedlinePlus

    ... Physical activity (exercise) fact sheet ePublications Physical activity (exercise) fact sheet How can physical activity improve my ... recent hip surgery More information on physical activity (exercise) For more information about physical activity (exercise), call ...

  10. Activation Energy

    NASA Technical Reports Server (NTRS)

    Gadeken, Owen

    2002-01-01

    Teaming is so common in today's project management environment that most of us assume it comes naturally. We further assume that when presented with meaningful and challenging work, project teams will naturally engage in productive activity to complete their tasks. This assumption is expressed in the simple (but false) equation: Team + Work = Teamwork. Although this equation appears simple and straightforward, it is far from true for most project organizations whose reality is a complex web of institutional norms based on individual achievement and rewards. This is illustrated by the very first successful team experience from my early Air Force career. As a young lieutenant, I was sent to Squadron Officer School, which was the first in the series of Air Force professional military education courses I was required to complete during my career. We were immediately formed into teams of twelve officers. Much of the course featured competition between these teams. As the most junior member of my team, I quickly observed the tremendous pressure to show individual leadership capability. At one point early in the course, almost everyone in our group was vying to become the team leader. This conflict was so intense that it caused us to fail miserably in our first outdoor team building exercise. We spent so much time fighting over leadership that we were unable to complete any of the events on the outdoor obstacle course. This complete lack of success was so disheartening to me that I gave our team little hope for future success. What followed was a very intense period of bickering, conflict, and even shouting matches as our dysfunctional team tried to cope with our early failures and find some way to succeed. British physician and researcher Wilfred Bion (Experiences in Groups, 1961) discovered that there are powerful psychological forces inherent in all groups that divert from accomplishing their primary tasks. To overcome these restraining forces and use the potential

  11. Staying Active: Physical Activity and Exercise

    MedlinePlus

    ... How much physical activity should I do each week? The Centers for Disease Control and Prevention recommend ... 150 minutes of moderate-intensity aerobic activity a week, along with muscle-strengthening activities on 2 days ...

  12. Nitroimidazole carboxamides as antiparasitic agents targeting Giardia lamblia, Entamoeba histolytica and Trichomonas vaginalis.

    PubMed

    Jarrad, A M; Debnath, A; Miyamoto, Y; Hansford, K A; Pelingon, R; Butler, M S; Bains, T; Karoli, T; Blaskovich, M A T; Eckmann, L; Cooper, M A

    2016-09-14

    Diarrhoeal diseases caused by the intestinal parasites Giardia lamblia and Entamoeba histolytica constitute a major global health burden. Nitroimidazoles are first-line drugs for the treatment of giardiasis and amebiasis, with metronidazole 1 being the most commonly used drug worldwide. However, treatment failures in giardiasis occur in up to 20% of cases and development of resistance to metronidazole is of concern. We have re-examined 'old' nitroimidazoles as a foundation for the systematic development of next-generation derivatives. Using this approach, derivatisation of the nitroimidazole carboxamide scaffold provided improved antiparasitic agents. Thirty-three novel nitroimidazole carboxamides were synthesised and evaluated for activity against G. lamblia and E. histolytica. Several of the new compounds exhibited potent activity against G. lamblia strains, including metronidazole-resistant strains of G. lamblia (EC50 = 0.1-2.5 μM cf. metronidazole EC50 = 6.1-18 μM). Other compounds showed improved activity against E. histolytica (EC50 = 1.7-5.1 μM cf. metronidazole EC50 = 5.0 μM), potent activity against Trichomonas vaginalis (EC50 = 0.6-1.4 μM cf. metronidazole EC50 = 0.8 μM) and moderate activity against the intestinal bacterial pathogen Clostridium difficile (0.5-2 μg/mL, cf. metronidazole = 0.5 μg/mL). The new compounds had low toxicity against mammalian kidney and liver cells (CC50 > 100 μM), and selected antiparasitic hits were assessed for human plasma protein binding and metabolic stability in liver microsomes to demonstrate their therapeutic potential.

  13. Inhibitors of Methionyl-tRNA Synthetase Have Potent Activity against Giardia intestinalis Trophozoites

    PubMed Central

    Ranade, Ranae M.; Zhang, Zhongsheng; Gillespie, J. Robert; Shibata, Sayaka; Verlinde, Christophe L. M. J.; Hol, Wim G. J.; Fan, Erkang

    2015-01-01

    The methionyl-tRNA synthetase (MetRS) is a novel drug target for the protozoan pathogen Giardia intestinalis. This protist contains a single MetRS that is distinct from the human cytoplasmic MetRS. A panel of MetRS inhibitors was tested against recombinant Giardia MetRS, Giardia trophozoites, and mammalian cell lines. The best compounds inhibited trophozoite growth at 500 nM (metronidazole did so at ∼5,000 nM) and had low cytotoxicity against mammalian cells, indicating excellent potential for further development as anti-Giardia drugs. PMID:26324270

  14. Enhancement of the antitrichomonal activity of 5-nitroimidazole derivatives by hydrogen peroxide.

    PubMed

    Mattana, A; Juliano, C; Picci, V; Franconi, F; Cappuccinelli, P

    1993-10-01

    The in vitro sensitivity of nine Trichomonas vaginalis isolates to commonly employed 5-nitroimidazoles (metronidazole, nimorazole, ornidazole and tinidazole) was evaluated in absence and in presence of sub-inhibitory concentrations of hydrogen peroxide (H2O2). Co-incubation with H2O2 and 5-nitroimidazole compounds decreased the MIC values of the strains exhibiting cross-resistance to these drugs. It was suggested that H2O2 produced in the inflammatory process during trichomonal infection could enhance the therapeutic effect of 5-nitroimidazole drugs.

  15. Radiosensitizing activity of 1-alkyl-3-nitropyrrolo-(2,3-b)-pyridine derivative

    SciTech Connect

    Jin, Y.Z.; Stratford, I.J.

    1989-02-01

    Radiosensitization characteristics of a newly synthesized N-(3,N'-morpholinpropyl)-2-(3-nitropyrrolo-(2,3-b)-pyridine -1-yl) ethanoic acid amide and the chemical basis of the action were studied. Partition coefficient, redox potentials for the one electron reduction of the compound were determined. This was confirmed by studies on the radiosensitization effect and cytotoxicity of the compound tested in vitro using Chinese hamster V79 cells. The results show that the sensitizing efficiency for this compound is C1.6 at a concentration of 0.5 mmol dm-3, which is similar to MISO. Its toxicity was not lower than that of MISO or metronidazole.

  16. Adolescent sexual activity.

    PubMed

    Braverman, P K; Strasburger, V C

    1993-11-01

    Adolescents are becoming sexually active at younger ages. One half of the adolescents in the United States are sexually active. This article reviews adolescent sexual activity, including rates of sexual activity, sexual practices, gay and lesbian youth, and factors affecting the initiation of sexual activity. In addition, adolescent pregnancy, with possible outcomes and effects on teen parents and their offspring, is discussed.

  17. Guide to Physical Activity

    MedlinePlus

    ... Families ( We Can! ) Health Professional Resources Guide to Physical Activity Physical activity is an important part of your ... to injury. Examples of moderate-intensity amounts of physical activity Common Chores Washing and waxing a car for ...

  18. Physical Activity Assessment

    Cancer.gov

    Current evidence convincingly indicates that physical activity reduces the risk of colon and breast cancer. Physical activity may also reduce risk of prostate cancer. Scientists are also evaluating potential relationships between physical activity and other cancers.

  19. The role of human cytochrome P450 enzymes in the formation of 2-hydroxymetronidazole: CYP2A6 is the high affinity (low Km) catalyst.

    PubMed

    Pearce, Robin E; Cohen-Wolkowiez, Michael; Sampson, Mario R; Kearns, Gregory L

    2013-09-01

    Despite metronidazole's widespread clinical use since the 1960s, the specific enzymes involved in its biotransformation have not been previously identified. Hence, in vitro studies were conducted to identify and characterize the cytochrome P450 enzymes involved in the formation of the major metabolite, 2-hydroxymetronidazole. Formation of 2-hydroxymetronidazole in human liver microsomes was consistent with biphasic, Michaelis-Menten kinetics. Although several cDNA-expressed P450 enzymes catalyzed 2-hydroxymetronidazole formation at a supratherapeutic concentration of metronidazole (2000 μM), at a "therapeutic concentration" of 100 μM only CYPs 2A6, 3A4, 3A5, and 3A7 catalyzed metronidazole 2-hydroxylation at rates substantially greater than control vector, and CYP2A6 catalyzed 2-hydroxymetronidazole formation at rates 6-fold higher than the next most active enzyme. Kinetic studies with these recombinant enzymes revealed that CYP2A6 has a Km = 289 μM which is comparable to the Km for the high-affinity (low-Km) enzyme in human liver microsomes, whereas the Km values for the CYP3A enzymes corresponded with the low-affinity (high-Km) component. The sample-to-sample variation in 2-hydroxymetronidazole formation correlated significantly with CYP2A6 activity (r ≥ 0.970, P < 0.001) at substrate concentrations of 100 and 300 μM. Selective chemical inhibitors of CYP2A6 inhibited metronidazole 2-hydroxylation in a concentration-dependent manner and inhibitory antibodies against CYP2A6 virtually eliminated metronidazole 2-hydroxylation (>99%). Chemical and antibody inhibitors of other P450 enzymes had little or no effect on metronidazole 2-hydroxylation. These results suggest that CYP2A6 is the primary catalyst responsible for the 2-hydroxylation of metronidazole, a reaction that may function as a marker of CYP2A6 activity both in vitro and in vivo.

  20. Political activity for physical activity: health advocacy for active transport

    PubMed Central

    2011-01-01

    Effective health advocacy is a priority for efforts to increase population participation in physical activity. Local councils are an important audience for this advocacy. The aim of the current study was to describe features of advocacy for active transport via submissions to city council annual plans in New Zealand, and the impact of an information sheet to encourage the health sector to be involved in this process. Written submissions to city council's annual consultation process were requested for 16 city councils over the period of three years (2007/08, 2008/09, and 2009/10). Submissions were reviewed and categories of responses were created. An advocacy information sheet encouraging health sector participation and summarising some of the evidence-base related to physical activity, active transport and health was released just prior to the 2009/10 submission time. Over the period of the study, city councils received 47,392 submissions, 17% of which were related to active transport. Most submissions came from city residents, with a small proportion (2%) from the health sector. The largest category of submissions was in support of pedestrian and cycling infrastructure, design and maintenance of facilities and additional features to support use of these transport modes. Health arguments featured prominently in justifications for active transport initiatives, including concerns about injury risk, obesity, physical inactivity, personal safety and facilities for people with disabilities. There was evidence that the information sheet was utilised by some health sector submitters (12.5%), providing tentative support for initiatives of this nature. In conclusion, the study provides novel information about the current nature of health advocacy for active transport and informs future advocacy efforts about areas for emphasis, such as health benefits of active transport, and potential alliances with other sectors such as environmental sustainability, transport and urban

  1. Ceftolozane/tazobactam: a novel cephalosporin/β-lactamase inhibitor combination with activity against multidrug-resistant gram-negative bacilli.

    PubMed

    Zhanel, George G; Chung, Phillip; Adam, Heather; Zelenitsky, Sheryl; Denisuik, Andrew; Schweizer, Frank; Lagacé-Wiens, Philippe R S; Rubinstein, Ethan; Gin, Alfred S; Walkty, Andrew; Hoban, Daryl J; Lynch, Joseph P; Karlowsky, James A

    2014-01-01

    plasma protein binding (20 %), is primarily eliminated via urinary excretion (≥92 %), and may require dose adjustments in patients with a creatinine clearance <50 mL/min. Time-kill experiments and animal infection models have demonstrated that the pharmacokinetic-pharmacodynamic index that is best correlated with ceftolozane's in vivo efficacy is the percentage of time in which free plasma drug concentrations exceed the minimum inhibitory concentration of a given pathogen (%fT >MIC), as expected of β-lactams. Two phase II clinical trials have been conducted to evaluate ceftolozane ± tazobactam in the settings of cUTIs and cIAIs. One trial compared ceftolozane 1,000 mg every 8 h (q8h) versus ceftazidime 1,000 mg q8h in the treatment of cUTI, including pyelonephritis, and demonstrated similar microbiologic and clinical outcomes, as well as a similar incidence of adverse effects after 7-10 days of treatment, respectively. A second trial has been conducted comparing ceftolozane/tazobactam 1,000/500 mg and metronidazole 500 mg q8h versus meropenem 1,000 mg q8h in the treatment of cIAI. A number of phase I and phase II studies have reported ceftolozane to possess a good safety and tolerability profile, one that is consistent with that of other cephalosporins. In conclusion, ceftolozane is a new cephalosporin with activity versus MDR organisms including P. aeruginosa. Tazobactam allows the broadening of the spectrum of ceftolozane versus β-lactamase-producing Gram-negative bacilli including ESBLs. Potential roles for ceftolozane/tazobactam include empiric therapy where infection by a resistant Gram-negative organism (e.g., ESBL) is suspected, or as part of combination therapy (e.g., with metronidazole) where a polymicrobial infection is suspected. In addition, ceftolozane/tazobactam may represent alternative therapy to the third-generation cephalosporins after treatment failure or for documented infections due to Gram-negative bacilli producing ESBLs

  2. Home Activities for Fours.

    ERIC Educational Resources Information Center

    Ferguson-Florissant School District, Ferguson, MO.

    These home learning activity guides have been developed for parents to use with their 4-year-old children. Most of the activities require only household items that are often thrown away and can be recycled for learning activities. Some require no materials at all. The guides frequently begin with a discussion of home activities; progress through…

  3. Active commuting to school

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Declines in physical activity levels have coincided with increasing rates of obesity in children. This is problematic because physical activity has been shown to attenuate weight gain in children. Active commuting to school is one way of increasing children's physical activity. However, given the hi...

  4. Civil Law: 12 Activities.

    ERIC Educational Resources Information Center

    Dresbach, Debra

    These learning activities on civil law are intended to supplement the secondary level Scholastic materials "Living Law." Case studies, simulations, and role-play activities are included. Information provided for each activity includes a brief overview, background information, teacher instructions and a description of each activity.…

  5. Increasing Youth Physical Activity with Activity Calendars

    ERIC Educational Resources Information Center

    Eckler, Seth

    2016-01-01

    Physical educators often struggle with ways to get their students to be active beyond the school day. One strategy to accomplish this is the use of physical activity calendars (PACs). The purpose of this article is to support the use of PACs and give practical advice for creating effective PACs.

  6. [Biological effects of electromagnetic radiation of extremely high frequencies combined with physiologically active compounds].

    PubMed

    Rogacheva, S M; Denisova, S A; Shul'gin, S V; Somov, A Iu; Kuznetsov, P E

    2008-01-01

    The study of the action of the electromagnetic radiation (EMR) of low intensity (10 microW/cm2) in the range of frequencies 120-170 GHz at the test-reaction of Infusoria Paramecium caudatum was carried out. The resonant character of the effects was established. The EMR action at 156.6 and 161.3 GHz caused the increase of infusorians mobility, the action at frequencies 151.8, 155.7, 167.1 GHz caused the mobility reduction. Isolated and combined with EMR effects of nicotine (10(-4)-10(-15) mol/l) and antimicrobial drug metronidazole (10(-5), 10(-8), 10(-9) mol/l) were investigated. The radiation at the frequency 167.1 GHz was shown to reduce the effect of nicotine (10(-9) mol/l) and to enhance the effect of metronidazole (10(-9) mol/l). This phenomenon may be explained by different effects of the substances in low concentration at the water hydrogen bonds net structure.

  7. Genotyping of Peroxisome Proliferator-Activated Receptor gamma in Iranian Patients with Helicobacter pylori Infection.

    PubMed

    Goudarzi, Hossein; Seyedjavadi, Sima Sadat; Fazeli, Maryam; Azad, Mehdi; Goudarzi, Mehdi

    2015-01-01

    Helicobacter pylori (H. pylori) infection as a serious problem in both adults and children can induce chronic gastritis, peptic ulcer disease (PUD), and possibly gastric cancer. The aim of the current study was to survey antibiotic resistance and also to determine influence of PPARγ polymorphism in patients with H. pylori infection. During an 11-month-period, 98 H. pylori isolates were collected from 104 biopsy specimens. In vitro susceptibility of H. pylori isolates to 4 antimicrobial agents metronidazole, clarithromycin, amoxicillin and tetracycline were assessed by quantitative method according to European Committee on Antimicrobial Susceptibility Testing (EUCAST) guideline. PPARγ polymorphism was determined using polymerase chain reaction-restriction fragment length polymorphism assay. The frequency of H. pylori infection in our study was 94.2%. In vitro susceptibility data showed that highest level of resistance was related to metronidazole (66.3%), and the majority of H. pylori isolates were highly susceptible to amoxicillin and tetracycline (94.9% and 96.9%, respectively). Genotypic frequencies were 25.5% for CC (Pro12Pro), 40.8% for GC (Pro12Ala) and 33.7% for GG (Ala12Ala). In our study, CG genotype had highest distributions among infected patients with H. pylori. The study suggests that the PPAR-γ Pro12Ala polymorphism could be evaluated as a potential genetic marker for susceptibility to gastric cancer in the presence of H. pylori infection.

  8. Cultural Activation of Consumers.

    PubMed

    Siegel, Carole E; Reid-Rose, Lenora; Joseph, Adriana M; Hernandez, Jennifer C; Haugland, Gary

    2016-02-01

    This column discusses "cultural activation," defined as a consumer's recognition of the importance of providing cultural information to providers about cultural affiliations, challenges, views about, and attitudes toward behavioral health and general medical health care, as well as the consumer's confidence in his or her ability to provide this information. An aid to activation, "Cultural Activation Prompts," and a scale that measures a consumer's level of activation, the Cultural Activation Measurement Scale, are described. Suggestions are made about ways to introduce cultural activation as a component of usual care.

  9. Smoking, physical activity, and active life expectancy.

    PubMed

    Ferrucci, L; Izmirlian, G; Leveille, S; Phillips, C L; Corti, M C; Brock, D B; Guralnik, J M

    1999-04-01

    The effect of smoking and physical activity on active and disabled life expectancy was estimated using data from the Established Populations for Epidemiologic Studies of the Elderly (EPESE). Population-based samples of persons aged > or = 65 years from the East Boston, Massachusetts, New Haven, Connecticut, and Iowa sites of the EPESE were assessed at baseline between 1981 and 1983 and followed for mortality and disability over six annual follow-ups. A total of 8,604 persons without disability at baseline were classified as "ever" or "never" smokers and doing "low," "moderate," or "high" level physical activity. Active and disabled life expectancies were estimated using a Markov chain model. Compared with smokers, men and women nonsmokers survived 1.6-3.9 and 1.6-3.6 years longer, respectively, depending on level of physical activity. When smokers were disabled and close to death, most nonsmokers were still nondisabled. Physical activity, from low to moderate to high, was significantly associated with more years of life expectancy in both smokers (9.5, 10.5, 12.9 years in men and 11.1, 12.6, 15.3 years in women at age 65) and nonsmokers (11.0, 14.4, 16.2 years in men and 12.7, 16.2, 18.4 years in women at age 65). Higher physical activity was associated with fewer years of disability prior to death. These findings provide strong and explicit evidence that refraining from smoking and doing regular physical activity predict a long and healthy life.

  10. Population Education. Awareness Activities.

    ERIC Educational Resources Information Center

    Brouse, Deborah E.

    1990-01-01

    Described are awareness activities that deal with human population growth, resources, and the environment. Activities include simulations, mathematical exercises, and discussions of the topic. Specific examples of what individuals can do to help are listed. (KR)

  11. Major operations and activities

    SciTech Connect

    Black, D.G.

    1995-06-01

    This section of the 1994 Hanford Site Environmental Report summarizes the major operations and activities on the site. These operations and activities include site management, waste management, environmental restoration and corrective actions, and research and technology development.

  12. Family Activities for Fitness

    ERIC Educational Resources Information Center

    Grosse, Susan J.

    2009-01-01

    This article discusses how families can increase family togetherness and improve physical fitness. The author provides easy ways to implement family friendly activities for improving and maintaining physical health. These activities include: walking, backyard games, and fitness challenges.

  13. Active magnetic regenerator

    DOEpatents

    Barclay, John A.; Steyert, William A.

    1982-01-01

    The disclosure is directed to an active magnetic regenerator apparatus and method. Brayton, Stirling, Ericsson, and Carnot cycles and the like may be utilized in an active magnetic regenerator to provide efficient refrigeration over relatively large temperature ranges.

  14. ACS Community Activities Contests

    NASA Astrophysics Data System (ADS)

    Burgener, Marisa

    2007-08-01

    The Committee on Community Activities and the Office of Community Activities announce the winners of the Illustrated Haiku Contest, Earth Day 2007 and the Poster Contest, National Chemistry Week 2006.

  15. Activity Theory and Ontology

    ERIC Educational Resources Information Center

    Peim, Nick

    2009-01-01

    This paper seeks to re-examine Yrio Engestrom's activity theory as a technology of knowledge designed to enable positive transformations of specific practices. The paper focuses on a key paper where Engestrom defines the nature and present state of activity theory. Beginning with a brief account of the relations between activity theory and…

  16. Measurement of Physical Activity.

    ERIC Educational Resources Information Center

    Dishman, Rod K.; Washburn, Richard A.; Schoeller, Dale A.

    2001-01-01

    Valid assessment of physical activity must be unobtrusive, practical to administer, and specific about physical activity type, frequency, duration, and intensity. Assessment methods can be categorized according to whether they provide direct or indirect (e.g., self-report) observation of physical activity, body motion, physiological response…

  17. Horticultural Practices. Activity Guides.

    ERIC Educational Resources Information Center

    Bania, Kent; Cummings, John, Ed.

    The 88 activity guides in this document are intended to supplement the initial or organized instruction of the agricultural teacher at the secondary educational level. Some of the activities require one student to complete, others may need two or more students working in a team. Some activities also require followup checking within a few days to…

  18. Highlights of 1981 activities

    NASA Technical Reports Server (NTRS)

    1981-01-01

    The highlights of NASA's 1981 activities are presented, including the results of the two flights of the space shuttle Columbia and the Voyager 2 encounter with Saturn. Accomplishments in the areas of space transportation operations; space science; aeronautical, energy, and space research and development; as well as space tracking, international activities, and 1981 launch activities are discussed.

  19. Bonus Activity Book.

    ERIC Educational Resources Information Center

    Learning, 1992

    1992-01-01

    Provides on-task activities to fill in unexpected extra moments in elementary classes. The activities require little preparation and take 5-15 minutes to complete. There are activities for math, language arts, social science, science, critical thinking, and computer. An outer space board game is also included. (SM)

  20. Activity Sheets. Draft Copy.

    ERIC Educational Resources Information Center

    Duke Power Company, Educational Services Dept., Charlotte, NC.

    This document consists of energy vocabulary activities, three games, worksheets, laboratory activities/exercises, and an introductory classroom exercise designed to introduce energy concepts to students. Vocabulary activities focus on coal and energy consumption. The three games (with instructions) focus on various aspects of energy and energy…

  1. Technology Learning Activities I.

    ERIC Educational Resources Information Center

    International Technology Education Association, Reston, VA.

    This guide contains 30 technology learning activities. Activities may contain all or some of the following: an introduction, objectives, materials and equipment, challenges, limitations, notes and investigations, resources and references used, and evaluation ideas. Activity titles are: (1) Occupations in Construction Technology; (2) Designing a…

  2. Technology Systems. Laboratory Activities.

    ERIC Educational Resources Information Center

    Brame, Ray; And Others

    This guide contains 43 modules of laboratory activities for technology education courses. Each module includes an instructor's resource sheet and the student laboratory activity. Instructor's resource sheets include some or all of the following elements: module number, course title, activity topic, estimated time, essential elements, objectives,…

  3. Computers + Student Activities Handbook.

    ERIC Educational Resources Information Center

    Masie, Elliott; Stein, Michele

    Designed to provide schools with the tools to start utilizing computers for student activity programs without additional expenditures, this handbook provides beginning computer users with suggestions and ideas for using computers in such activities as drama clubs, yearbooks, newspapers, activity calendars, accounting programs, room utilization,…

  4. Climate Change: An Activity.

    ERIC Educational Resources Information Center

    Lewis, Garry

    1995-01-01

    Presents a segment of the Geoscience Education booklet, Climate Change, that contains information and activities that enable students to gain a better appreciation of the possible effects human activity has on the Earth's climate. Describes the Terrace Temperatures activity that leads students through an investigation using foraminifera data to…

  5. Vestibular activation of sympathetic nerve activity

    NASA Technical Reports Server (NTRS)

    Ray, C. A.; Carter, J. R.

    2003-01-01

    AIM: The vestibulosympathetic reflex refers to sympathetic nerve activation by the vestibular system. Animal studies indicate that the vestibular system assists in blood pressure regulation during orthostasis. Although human studies clearly demonstrate activation of muscle sympathetic nerve activity (MSNA) during engagement of the otolith organs, the role of the vestibulosympathetic reflex in maintaining blood pressure during orthostasis is not well-established. Examination of the vestibulosympathetic reflex with other cardiovascular reflexes indicates that it is a powerful and independent reflex. Ageing, which is associated with an increased risk for orthostatic hypotension, attenuates the vestibulosympathetic reflex. The attenuated reflex is associated with a reduction in arterial pressure. CONCLUSION: These findings suggest that the vestibulosympathetic reflex assists in blood pressure regulation in humans, but future studies examining this reflex in other orthostatically intolerant populations are necessary to address this hypothesis.

  6. Metabolism Supports Macrophage Activation

    PubMed Central

    Langston, P. Kent; Shibata, Munehiko; Horng, Tiffany

    2017-01-01

    Macrophages are found in most tissues of the body, where they have tissue- and context-dependent roles in maintaining homeostasis as well as coordinating adaptive responses to various stresses. Their capacity for specialized functions is controlled by polarizing signals, which activate macrophages by upregulating transcriptional programs that encode distinct effector functions. An important conceptual advance in the field of macrophage biology, emerging from recent studies, is that macrophage activation is critically supported by metabolic shifts. Metabolic shifts fuel multiple aspects of macrophage activation, and preventing these shifts impairs appropriate activation. These findings raise the exciting possibility that macrophage functions in various contexts could be regulated by manipulating their metabolism. Here, we review the rapidly evolving field of macrophage metabolism, discussing how polarizing signals trigger metabolic shifts and how these shifts enable appropriate activation and sustain effector activities. We also discuss recent studies indicating that the mitochondria are central hubs in inflammatory macrophage activation. PMID:28197151

  7. Activated carbon from biomass

    NASA Astrophysics Data System (ADS)

    Manocha, S.; Manocha, L. M.; Joshi, Parth; Patel, Bhavesh; Dangi, Gaurav; Verma, Narendra

    2013-06-01

    Activated carbon are unique and versatile adsorbents having extended surface area, micro porous structure, universal adsorption effect, high adsorption capacity and high degree of surface reactivity. Activated carbons are synthesized from variety of materials. Most commonly used on a commercial scale are cellulosic based precursors such as peat, coal, lignite wood and coconut shell. Variation occurs in precursors in terms of structure and carbon content. Coir having very low bulk density and porous structure is found to be one of the valuable raw materials for the production of highly porous activated carbon and other important factor is its high carbon content. Exploration of good low cost and non conventional adsorbent may contribute to the sustainability of the environment and offer promising benefits for the commercial purpose in future. Carbonization of biomass was carried out in a horizontal muffle furnace. Both carbonization and activation were performed in inert nitrogen atmosphere in one step to enhance the surface area and to develop interconnecting porosity. The types of biomass as well as the activation conditions determine the properties and the yield of activated carbon. Activated carbon produced from biomass is cost effective as it is easily available as a waste biomass. Activated carbon produced by combination of chemical and physical activation has higher surface area of 2442 m2/gm compared to that produced by physical activation (1365 m2/gm).

  8. Factor XII Contact Activation.

    PubMed

    Naudin, Clément; Burillo, Elena; Blankenberg, Stefan; Butler, Lynn; Renné, Thomas

    2017-03-27

    Contact activation is the surface-induced conversion of factor XII (FXII) zymogen to the serine protease FXIIa. Blood-circulating FXII binds to negatively charged surfaces and this contact to surfaces triggers a conformational change in the zymogen inducing autoactivation. Several surfaces that have the capacity for initiating FXII contact activation have been identified, including misfolded protein aggregates, collagen, nucleic acids, and platelet and microbial polyphosphate. Activated FXII initiates the proinflammatory kallikrein-kinin system and the intrinsic coagulation pathway, leading to formation of bradykinin and thrombin, respectively. FXII contact activation is well characterized in vitro and provides the mechanistic basis for the diagnostic clotting assay, activated partial thromboplastin time. However, only in the past decade has the critical role of FXII contact activation in pathological thrombosis been appreciated. While defective FXII contact activation provides thromboprotection, excess activation underlies the swelling disorder hereditary angioedema type III. This review provides an overview of the molecular basis of FXII contact activation and FXII contact activation-associated disease states.

  9. Marine Biology Activities. Ocean Related Curriculum Activities.

    ERIC Educational Resources Information Center

    Pauls, John

    The ocean affects all of our lives. Therefore, awareness of and information about the interconnections between humans and oceans are prerequisites to making sound decisions for the future. Project ORCA (Ocean Related Curriculum Activities) has developed interdisciplinary curriculum materials designed to meet the needs of students and teachers…

  10. Patterns in Active Nematics

    NASA Astrophysics Data System (ADS)

    Yeomans, Julia M.

    Active systems, from bacterial suspensions to cellular monolayers, are continuously driven out of equilibrium by local injection of energy from their constituent elements and exhibit turbulent-like, chaotic patterns. We describe how active systems can be stabilised by tuning a physical feature of the system, friction. We demonstrate how the crossover between wet active systems, whose behaviour is dominated by hydrodynamics, and dry active matter where any flow is screened, can be achieved by using friction as a control parameter and demonstrate vortex ordering at the wet-dry crossover. We show that the self organisation of vortices into lattices is accompanied by the spatial ordering of topological defects leading to active crystal-like structures. The emergence of vortex lattices which leads to the positional ordering of topological defects may be a useful step towards the design and control of active materials.

  11. Activated recombinant adenovirus proteinases

    DOEpatents

    Anderson, C.W.; Mangel, W.F.

    1999-08-10

    This application describes methods and expression constructs for producing activatable recombinant adenovirus proteinases. Purified activatable recombinant adenovirus proteinases and methods of purification are described. Activated adenovirus proteinases and methods for obtaining activated adenovirus proteinases are further included. Isolated peptide cofactors of adenovirus proteinase activity, methods of purifying and identifying peptide cofactors are also described. Antibodies immunoreactive with adenovirus proteinases, immunospecific antibodies, and methods for preparing them are also described. Other related methods and materials are also described. 29 figs.

  12. Activated recombinant adenovirus proteinases

    DOEpatents

    Anderson, Carl W.; Mangel, Walter F.

    1999-08-10

    This application describes methods and expression constructs for producing activatable recombinant adenovirus proteinases. Purified activatable recombinant adenovirus proteinases and methods of purification are described. Activated adenovirus proteinases and methods for obtaining activated adenovirus proteinases are further included. Isolated peptide cofactors of adenovirus proteinase activity, methods of purifying and identifying said peptide cofactors are also described. Antibodies immunoreactive with adenovirus proteinases, immunospecific antibodies, and methods for preparing them are also described. Other related methods and materials are also described.

  13. Activity in distant comets

    NASA Technical Reports Server (NTRS)

    Luu, Jane X.

    1992-01-01

    Activity in distant comets remains a mystery in the sense that we still have no complete theory to explain the various types of activity exhibited by different comets at large distances. This paper explores the factors that should play a role in determining activity in a distant comet, especially in the cases of comet P/Tempel 2, comet Schwassmann-Wachmann 1, and 2060 Chiron.

  14. Thermally Activated Driver

    NASA Technical Reports Server (NTRS)

    Kinard, William H.; Murray, Robert C.; Walsh, Robert F.

    1987-01-01

    Space-qualified, precise, large-force, thermally activated driver (TAD) developed for use in space on astro-physics experiment to measure abundance of rare actinide-group elements in cosmic rays. Actinide cosmic rays detected using thermally activated driver as heart of event-thermometer (ET) system. Thermal expansion and contraction of silicone oil activates driver. Potential applications in fluid-control systems where precise valve controls are needed.

  15. [Biomedical activity of biosurfactants].

    PubMed

    Krasowska, Anna

    2010-07-23

    Biosurfactants, amphiphilic compounds, synthesized by microorganisms have surface, antimicrobial and antitumor properties. Biosurfactants prevent adhesion and biofilms formation by bacteria and fungi on various surfaces. For many years microbial surfactants are used as antibiotics with board spectrum of activity against microorganisms. Biosurfactants act as antiviral compounds and their antitumor activities are mediated through induction of apoptosis. This work presents the current state of knowledge related to biomedical activity of biosurfactants.

  16. NASA metrication activities

    NASA Technical Reports Server (NTRS)

    Vlannes, P. N.

    1978-01-01

    NASA's organization and policy for metrification, history from 1964, NASA participation in Federal agency activities, interaction with nongovernmental metrication organizations, and the proposed metrication assessment study are reviewed.

  17. Active Flow Control Activities at NASA Langley

    NASA Technical Reports Server (NTRS)

    Anders, Scott G.; Sellers, William L., III; Washburn, Anthony E.

    2004-01-01

    NASA Langley continues to aggressive