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Sample records for bioadhesive controlled metronidazole

  1. Zwitterionic-based stainless steel with well-defined polysulfobetaine brushes for general bioadhesive control.

    PubMed

    Sin, Mei-Chan; Sun, Yi-Ming; Chang, Yung

    2014-01-22

    Stainless steels are widely used as orthopaedic and dental implant; however, bioadhesion in the case of thrombosis, inflammation, and infection is one of their major limitations. One way to tackle this problem is to graft the stainless steel surface with a zwitterionic polymer known for being anti-bioadhesive. Controlled atom transfer radical polymerization (ATRP) of zwitterionic poly(sulfobetaine methacrylate) (polySBMA) grafted from biomedical grade stainless steel surface was employed in this study. The interactions of polySBMA-grafted surfaces with biomacromolecules were demonstrated in vitro by the adhesion tests of plasma protein, blood cells, human MG63 osteoblast- and HT1080 fibroblast-like cells in biological complex media to evaluate their bioadhesive properties. Anti-microbial effects were also assessed for two most ordinary seen clinical bacteria, i.e., Escherichia coli and Staphylococcus epidermidis. Results showed that polySBMA-grafted surface exhibited evident bioadhesion resistance and conferring antibacterial efficacy. This work is also dedicated to deduce the effectiveness of polySBMA brushes' conformational structure on the prevention of bioadhesion. To this aim, the anti-bioadhesive effect of polySBMA brushes prepared by dopamine- and silane-surfaced immobilization method was evaluated. Results show that polySBMA grafted from immobilized polydopamine interfacial layers achieved better bioadhesion resistance, which could be causally related to their greater grafting coverage, flexible brush conformational structures, and greater hydration capabilities. PMID:24351074

  2. Formulation development of oral controlled release tablets of hydralazine: optimization of drug release and bioadhesive characteristics.

    PubMed

    Singh, Bhupinder; Pahuja, Sonia; Kapil, Rishi; Ahuja, Naveen

    2009-03-01

    The current study involves development of oral bioadhesive hydrophilic matrices of hydralazine hydrochloride, and optimization of their in vitro drug release profile and ex vivo bioadhesion against porcine gastric mucosa. A 32 central composite design was employed to systematically optimize the drug delivery formulations containing two polymers, viz., carbomer and hydroxypropyl methyl cellulose. Response surface plots were drawn and optimum formulations were selected by brute force searches. Validation of the formulation optimization study indicated a very high degree of prognostic ability. The study successfully undertook the development of an optimized once-a-day formulation of hydralazine with excellent bioadhesive and controlled release characteristics.

  3. Bioadhesive polymers as platforms for oral controlled drug delivery II: synthesis and evaluation of some swelling, water-insoluble bioadhesive polymers

    SciTech Connect

    Ch'ng, H.S.; Park, H.; Kelly, P.; Robinson, J.R.

    1985-04-01

    A series of cross-linked, swellable polymers was sythesized from monomers such as acrylic acid, methacrylic acid, and others with various cross-linking agents to produce a range of polymers differing in charge densities and hydrophobicity. The densities, rate, and extent of hydration of the polymers were determined. An increase in the number of hydrophobic groups in the polymer structure reduced hydration whereas the density of the polymer was unaffected. A sensitive in vitro method for measuring adhesion of polymer to tissue from the rabbit stomach was developed. Polymers of acrylic acid loosely cross-linked (0.3%, w/w) with three different agents, divinyl glycol, 2,5-dimethyl-1,5-hexadiene, and divinylbenzene, showed the same degree of bioadhesion while poly(methacrylic acid-divinylbenzene) showed reduced bioadhesion. The small percent of cross-linking agent, irrespective of physicochemical properties, did not contribute substantially to bioadhesion, whereas the starting monomer had a large effect. The effect of pH on the bioadhesion of poly(acrylic acid-divinyl glycol) was studied at constant temperature, ionic strength, and osmolality. The polymer showed maximum adhesion at pH 5 and 6 and a minimum at pH 7. Gastrointestinal transit studies of cross-linked polymers in rats were studied. Poly(acrylic acid-divinyl glycol) and poly(methacrylic acid-divinylbenzene) were shown to have substantially longer GI transit times than the control, Amberlite 200 resin beads. The delay in transit time was due to bioadhesion of the polymer to the mucin-epithelial cell surface which was clearly observable on animal autopsy. The acrylic acid polymer showed a longer GI transit time than the methacrylic acid polymer, and this in vivo GI transit result is consistent with in vitro bioadhesion test results.

  4. Bioadhesive polymers as platforms for oral controlled drug delivery III: oral delivery of chlorothiazide using a bioadhesive polymer.

    PubMed

    Longer, M A; Ch'ng, H S; Robinson, J R

    1985-04-01

    Bioadhesive polymers that bind to the gastric mucin or epithelial cell surface are useful in drug delivery for the purposes of (a) retaining a dosage from in the GI tract and (b) increasing the intimacy and duration of contact of drug with the absorbing membrane. Polycarbophil has previously been shown to have bioadhesive properties in the rat stomach and small intestine and was employed in the present study with a sustained-release delivery system to demonstrate improved drug delivery. Using chlorothiazide as the model drug, drug containing albumin beads were prepared and used as the sustained-release system. The beads were physically mixed with equally sized particles of polycarbophil and placed in a capsule to produce a bioadhesive dosage form. When the dosage form contacts the stomach, the gelatin capsule dissolves, exposing the polycarbophil to the bathing fluid. The bioadhesive polymer rapidly hydrates, retaining the albumin beads and attaching to the mucin coating of the stomach. Plasma drug levels in rats showed a longer duration of action and greater bioavailability for the bioadhesive dosage form than for either albumin beads or drug powder alone. The results suggest that the principle of bioadhesion can significantly improve therapy, due to a reduced rate of gastric emptying, an increase in contact time, and the intimacy of contact of the drug with the absorbing membrane.

  5. Controlled synthesis of N,N,N-trimethyl chitosan for modulated bioadhesion and nasal membrane permeability.

    PubMed

    Pardeshi, Chandrakantsing V; Belgamwar, Veena S

    2016-01-01

    In an experiment to explore the bioadhesion, biocompatibility, and membrane permeation properties, the controlled synthesis of N,N,N-trimethyl chitosan (TMC) was carried out by two-step reductive methylation of chitosan (CHT). Methylation was confirmed by (1)H NMR (δ=3.1 ppm) and FTIR analysis (CH stretch at 1,485 cm(-1)). The TMC was further characterized by DSC, TGA, XRD, HR-TEM, SEM, and elemental analysis. Findings revealed improved solubility, enhanced viscosity, increased swelling index and higher molecular weight of TMC over CHT. Comparative evaluation validated increased bioadhesion potential, and improved ex vivo biocompatibility of TMC compared to CHT. Increased bioadhesion of TMC NPs over CHT NPs can be attributed to the strong electrostatic interactions between cationic amino groups with anionic sialic and sulfonic acid moieties contained in the mucin of the nasal mucus. Ex vivo biocompatibility studies suggested that the NP formulations of both biopolymers were biocompatible and could be applied safely on the nasal epithelium. Ex vivo permeation studies executed on excised cattle nasal mucosa illustrated improved permeability of TMC NPs over CHT NPs. In the author's opinion, two-step reductive methylation of CHT could be an attractive strategy to improve its solubility, bioadhesion, and permeation characteristics without affecting biocompatibility across the mucosal surfaces.

  6. Chitosan-polycarbophil interpolyelectrolyte complex as an excipient for bioadhesive matrix systems to control macromolecular drug delivery.

    PubMed

    Lu, Zhilei; Chen, Weiyang; Hamman, Josias H; Ni, Jian; Zhai, Xiaoling

    2008-01-01

    The in vitro performance of monolithic matrix systems containing the interpolyelectrolyte complex between chitosan and polycarbophil as excipient was evaluated in terms of their swelling, bioadhesive, and drug release properties. The different matrix systems showed excellent swelling properties without erosion, except for the formulation containing the highest quantity chitosan-polycarbophil complex that exhibited surface erosion in addition to swelling. All the different matrix systems exhibited significantly higher bioadhesive properties than the control group. Furthermore, they showed controlled insulin release without an initial burst release effect. However, only the matrix system that exhibited surface erosion in combination with swelling approached zero-order release.

  7. Bioadhesive control of plasma proteins and blood cells from umbilical cord blood onto the interface grafted with zwitterionic polymer brushes.

    PubMed

    Chang, Yu; Chang, Yung; Higuchi, Akon; Shih, Yu-Ju; Li, Pei-Tsz; Chen, Wen-Yih; Tsai, Eing-Mei; Hsiue, Ging-Ho

    2012-03-01

    In this work, bioadhesive behavior of plasma proteins and blood cells from umbilical cord blood (UCB) onto zwitterionic poly(sulfobetaine methacrylate) (polySBMA) polymer brushes was studied. The surface coverage of polySBMA brushes on a hydrophobic polystyrene (PS) well plate with surface grafting weights ranging from 0.02 mg/cm(2) to 0.69 mg/cm(2) can be effectively controlled using the ozone pretreatment and thermal-induced radical graft-polymerization. The chemical composition, grafting structure, surface hydrophilicity, and hydration capability of prepared polySBMA brushes were determined to illustrate the correlations between grafting properties and blood compatibility of zwitterionic-grafted surfaces in contact with human UCB. The protein adsorption of fibrinogen in single-protein solutions and at complex medium of 100% UCB plasma onto different polySBMA brushes with different grafting coverage was measured by enzyme-linked immunosorbent assay (ELISA) with monoclonal antibodies. The grafting density of the zwitterionic brushes greatly affects the PS surface, thus controlling the adsorption of fibrinogen, the adhesion of platelets, and the preservation of hematopoietic stem and progenitor cells (HSPCs) in UCB. The results showed that PS surfaces grafted with polySBMA brushes possess controllable hydration properties through the binding of water molecules, regulating the bioadhesive and bioinert characteristics of plasma proteins and blood platelets in UCB. Interestingly, it was found that the polySBMA brushes with an optimized grafting weight of approximately 0.1 mg/cm(2) at physiologic temperatures show significant hydrated chain flexibility and balanced hydrophilicity to provide the best preservation capacity for HSPCs stored in 100% UCB solution for 2 weeks. This work suggests that, through controlling grafting structures, the hemocompatible nature of grafted zwitterionic polymer brushes makes them well suited to the molecular design of regulated

  8. Adjustable bioadhesive control of PEGylated hyperbranch brushes on polystyrene microplate interface for the improved sensitivity of human blood typing.

    PubMed

    Chen, Yan-Wen; Chang, Yung; Lee, Rong-Ho; Li, Wen-Tyng; Chinnathambi, Arunachalam; Alharbi, Sulaiman Ali; Hsiue, Ging-Ho

    2014-08-01

    A PEGylated 96-well polystyrene (PS) microplate was first introduced for applications in high-throughput screening for selective blood typing to minimize the risks in blood transfusions. Herein, we present a hemocompatible PS 96-well microplate with adjustable PEGylated hyperbranch brush coverage prepared by ozone pretreated activation and thermally induced surface PEGylation. The grafting properties, hydration capacity, and blood compatibility of the PEGylated hyperbrush immobilized PS surfaces in human blood were illustrated by the combined chemical and physical properties of the surface, and the dependence of the specific absorption of human plasma fibrinogen onto the PEGylated surfaces on the grafting density was analyzed by monoclonal antibodies. The surface coverage of PEGylated brushes plays a major role in the bioadhesive properties of modified PS microplates, which in turn control the level of agglutination sensitivity in blood typing. The bioadhesive resistance toward proteins, platelets, and erythrocytes in human whole blood showed a correlation to the controlled hydration properties of the PEGylated hyperbrush-modified surfaces. Therefore, we suggested that the surface coverage of PEGylated hyperbrushes on PS surfaces can increase the sensitivity of cross-matching blood agglutination by up to 16-fold compared to that of the conventional 96-well virgin PS due to the regulated biorecognition of hematocrit and antibodies of the PEGylated hyperbrush-modified surfaces. PMID:25022949

  9. Metronidazole Topical

    MedlinePlus

    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 usually is ... the medication. Apply a thin layer of cream, lotion, or gel and rub it gently into the ...

  10. Metronidazole Oral

    MedlinePlus

    Metronidazole comes as a tablet to take by mouth. It is usually taken two or three times ... vomiting diarrhea upset stomach loss of appetite dry mouth; sharp, unpleasant metallic taste dark or reddish-brown ...

  11. Compliance of bio-adhesive substrates controls the kinetics of membrane-substrate association.

    PubMed

    Sarvestani, Alireza S

    2010-10-21

    Mechanical stiffness of bio-adhesive substrates is one of the major regulators of the cell adhesion and migration. In this study, we propose a theoretical model for the spontaneous growth of focal adhesion (FA) sites, on compliant elastic substrates, at the early stages of cellular adhesion. Using a purely thermodynamic approach, we demonstrate that the rate of membrane-substrate association decreases with increasing the compliance of the substrate. This can be considered as a reason for smaller spread area of the FA points after the stabilization of adhesion on compliant substrates, as reported by experiments. We also show that the extent to which the compliance of the substrate modulates the growth rate of adhesion site depends on the areal density of cell-adhesive ligands on the substrate. PMID:20655930

  12. 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).

  13. A microtensiometer for the analysis of bioadhesive microspheres.

    PubMed

    Chickering, D E; Harris, W P; Mathiowitz, E

    1995-01-01

    Bioadhesive polymer microspheres are potential vehicles for the delivery of bioactive agents to mucosal tissues. Bioadhesive delivery devices could improve drug absorption, enhance bioavailability, and increase patient compliance by minimizing dosing regimens. Identification of bioadhesive materials is the first phase in developing bioadhesive drug delivery systems. Additionally, quantification and analysis of the bioadhesive event are essential to successful development of a new generation of adhesive delivery systems. A unique, microbalance-based instrument was developed to analyze bioadhesive forces between polymer microspheres and mucosal tissue segments. A contact angle analyzer, with a custom-made physiologic tissue chamber, was linked to a computer via the serial port. Software was used to modify the microbalance operation to behave as a microtensiometer with a sensitivity of 0.1 microN. After mounting a microsphere and tissue segment in the balance and adjusting the experimental settings, the instrument performs a tensile experiment and automatically determines the following parameters: compressive deformation, peak compressive load, compressive work, yield point, deformation to yield, returned work, peak tensile load, deformation to peak tensile load, fracture strength, deformation to failure, and tensile work. Using this device the authors identified several bioadhesive materials ideally suited for orally-delivered, controlled-release systems. GI-transit studies in rats showed strong correlation between increased GI-residence time and strong bioadhesive interactions. PMID:8574265

  14. Metronidazole Resistance in Clostridium difficile Is Heterogeneous▿

    PubMed Central

    Peláez, T.; Cercenado, E.; Alcalá, L.; Marín, M.; Martín-López, A.; Martínez-Alarcón, J.; Catalán, P.; Sánchez-Somolinos, M.; Bouza, E.

    2008-01-01

    At our institution, the prevalence of clinical isolates of Clostridium difficile with resistance to metronidazole is 6.3%. We observed that initial metronidazole MICs of 16 to 64 mg/liter against toxigenic, primary fresh C. difficile isolates, as determined by agar dilution, decreased to 0.125 mg/liter after the isolates were thawed. In this study, we examined the possibility of heterogeneous or inducible resistance. Totals of 14 metronidazole-resistant and 10 metronidazole-susceptible clinical isolates of toxigenic C. difficile were studied. The isolates were investigated for the presence of nim genes by PCR. After the isolates were thawed, susceptibility testing was done by agar dilution, by disc diffusion using a 5-μg metronidazole disc, and by the Etest method. An experiment for determining the effect of prolonged exposure to metronidazole was applied to all resistant isolates and to susceptible control strains. None of the isolates presented the nim genes. All initially metronidazole-resistant C. difficile isolates became susceptible after thawing; however, they presented slow-growing subpopulations within the inhibition zones of both the disk and the Etest strip. All metronidazole-susceptible isolates remained homogeneously susceptible by both methods. After prolonged exposure in vitro to metronidazole, no zone of inhibition was found around the 5-μg disk in any of the metronidazole-resistant isolates, and the MICs as determined by the Etest method ranged from 0.125 to >256 mg/liter, with colonies growing inside the inhibition zone. Our results indicate that (i) resistance to metronidazole was not due to the presence of nim genes, (ii) resistance to metronidazole in toxigenic C. difficile isolates is heterogeneous, and (iii) prolonged exposure to metronidazole can select for in vitro resistance. We recommend routine performance of the disk diffusion method (5-μg metronidazole disk) with primary fresh C. difficile isolates in order to ensure that

  15. Bioadhesive okra polymer based buccal patches as platform for controlled drug delivery.

    PubMed

    Kaur, Gurpreet; Singh, Deepinder; Brar, Vivekjot

    2014-09-01

    In the present investigation, polysaccharide from the Okra fruits (Hibiscus esculentus) was extracted, characterized and explored for its mucoadhesive potential. Mucoadhesive films of okra polymer (OP) were prepared by solvent casting method based on 3(2) factorial design. For these studies, OP (2.0%, 2.5%, 3.0%, w/v) and glycerol (plasticizer) (0.25%, 0.50%, 0.75%, v/v) were taken as independent variables while tensile strength, mucoadhesive strength, contact angle, swelling index and residence time as dependent variables. The developed films were evaluated for their physicochemical, mechanical and electrical properties. The formulated films were found to be smooth, flexible, and displayed adequate mucoadhesive and tensile strength. Their near neutral pH and negative hemolytic studies indicated their non-irritability and biocompatible nature with biological tissues. The formulation comprising of 3% OP and 0.5% glycerol (F8) was found to exhibit optimum mechanical properties. Further, optimized film was loaded with zolmitriptan (model drug) to determine its drug release profiles. In vitro and ex vivo drug release studies demonstrated a controlled release of zolmitriptan over a period of 8h in simulated salivary fluid (SSF) pH 6.8, with the correlation coefficient values indicating its non-Fickian kinetics. Thus, OP can be used as a promising biomaterial for controlled drug delivery.

  16. Bioadhesive okra polymer based buccal patches as platform for controlled drug delivery.

    PubMed

    Kaur, Gurpreet; Singh, Deepinder; Brar, Vivekjot

    2014-09-01

    In the present investigation, polysaccharide from the Okra fruits (Hibiscus esculentus) was extracted, characterized and explored for its mucoadhesive potential. Mucoadhesive films of okra polymer (OP) were prepared by solvent casting method based on 3(2) factorial design. For these studies, OP (2.0%, 2.5%, 3.0%, w/v) and glycerol (plasticizer) (0.25%, 0.50%, 0.75%, v/v) were taken as independent variables while tensile strength, mucoadhesive strength, contact angle, swelling index and residence time as dependent variables. The developed films were evaluated for their physicochemical, mechanical and electrical properties. The formulated films were found to be smooth, flexible, and displayed adequate mucoadhesive and tensile strength. Their near neutral pH and negative hemolytic studies indicated their non-irritability and biocompatible nature with biological tissues. The formulation comprising of 3% OP and 0.5% glycerol (F8) was found to exhibit optimum mechanical properties. Further, optimized film was loaded with zolmitriptan (model drug) to determine its drug release profiles. In vitro and ex vivo drug release studies demonstrated a controlled release of zolmitriptan over a period of 8h in simulated salivary fluid (SSF) pH 6.8, with the correlation coefficient values indicating its non-Fickian kinetics. Thus, OP can be used as a promising biomaterial for controlled drug delivery. PMID:25036601

  17. Preparation and characterization of bioadhesive controlled-release gels of cidofovir for vaginal delivery.

    PubMed

    Tuğcu-Demiröz, Fatmanur; Acartürk, Füsun; Özkul, Aykut

    2015-01-01

    The aim of this study was to develop mucoadhesive and thermosensitive gels for vaginal delivery that would be able to provide a controlled release of the model drug, cidofovir. The study also monitored the drug's potential antiviral properties. Cidofovir was put into the form of a vaginal gel, using mucoadhesive and thermosensitive polymers such as chitosan, Carbopol 974P, HPMC, and poloxamer 407. The physicopharmaceutical properties and stability of the vaginal gel formulations were evaluated. The gel formulation which was prepared with HPMC K100M exhibited the highest viscosity, as well as maximum adhesiveness, cohesiveness, and mucoadhesion values. The results of antiviral activity studies, which used the bovine herpes virus type 1 virus infection in vitro model using Vero cells, demonstrated the antiherpetic effect of the cidofovir gel containing HPMC K100M, at least under in vitro conditions. The study found that a mucoadhesive vaginal gel containing cidofovir can be a promising and innovative alternative therapeutic system for the treatment of genital herpes simplex virus and human papilloma virus induced infections in women. PMID:26300445

  18. Metronidazole induced cerebellar ataxia

    PubMed Central

    Hari, Aditya; Srikanth, B. Akshaya; Lakshmi, G. Sriranga

    2013-01-01

    Metronidazole is a widely used antimicrobial usually prescribed by many specialist doctors for a short duration of 10-15 days. Prolonged use of metronidazole is rare. The present case is of a patient who used the drug for 4 months and developed peripheral neuropathy, convulsions, and cerebellar ataxia. He was treated with diazepam and levetiracetam. The patient recovered completely following discontinuation of metronidazole. PMID:23833378

  19. Comparing the Therapeutic Effects of Garlic Tablet and Oral Metronidazole on Bacterial Vaginosis: A Randomized Controlled Clinical Trial

    PubMed Central

    Mohammadzadeh, Farnaz; Dolatian, Mahrokh; Jorjani, Masoome; Alavi Majd, Hamid; Borumandnia, Nasrin

    2014-01-01

    Background: Bacterial vaginosis (BV) is one of the most common gynecological infections during reproductive age. Although metronidazole is one of the most effective medications recommended as the first-line treatment, it has various side effects. Because of the side effects and contraindications of some chemical medicines, using herbs has been investigated in treating BV. Objectives: The aim of this study was to compare the effect of garlic tablet (Garsin) and oral metronidazole in clinical treatment of the BV in women referred to Resalat Health Center, affiliated with Mazandaran University of Medical Sciences, in 2013. Patients and Methods: This randomized clinical trial was conducted on 120 married women aged 18 to 44 years who were diagnosed with BV by Amsel’s clinical criteria and Gram staining. Enrolled women were randomly allocated to two groups of 60 patients and were treated with either garlic tablet or oral metronidazole for seven days. Amsel’s criteria and Gram stain were assessed seven to ten days after beginning the treatment period and side effects were registered. Results: Amsel’s criteria were significantly decreased after treatment with garlic or metronidazole (70% and 48.3%, respectively; P < 0.001). Therapeutic effects of garlic on BV were similar to that of metronidazole (63.3% and 48.3%, respectively; P = 0.141). There were significant differences between the two treatment groups in terms of side effects; metronidazole was associated with more complications (P = 0.032). Conclusions: This study reveals that garlic could be a suitable alternative for metronidazole in treatment of BV in those interested in herbal medicines or those affected by side effects of metronidazole. PMID:25237588

  20. Metronidazole (Flagyl) and Pregnancy

    MedlinePlus

    ... shown to cause changes in genetic material and cancer in animals. At this time, it has not been found to have these effects in humans. One study that followed several hundred women for 20 years did not find an increase in cancer. Can I take metronidazole while breastfeeding? Metronidazole gets ...

  1. Melt extrusion bioadhesive delivery of diclofenac sodium granules using theobroma oil.

    PubMed

    Attama, A A; Adikwu, M U

    2004-05-01

    Carbopol 941 (C-941), a bioadhesive polymer and theobroma oil (TEO) were used in the formulation of melt extrusion bioadhesive tablets (MEBT) of diclofenac (DC). Different batches of the MEBT were formulated using different combinations of C-941 granules containing DC and TEO. The bioadhesive properties of the tablets were studied using a tensiometer by measuring the bioadhesive strength generated when the tablet interacts with the mucus of everted hog jejunum. Some physical properties of the tablets evaluated were weight uniformity, crushing strength, friability, tablet thickness and diameter liquefaction time and absolute drug content. Release of DC from the MEBT was carried out in simulated intestinal fluid (SIF), pH 7.2. The tablets had low liquefaction times and were highly bioadhesive. Result of the study indicated that TEO could be used in the formulation of MEBT of DC granulated with C-941 for prolonged and controlled delivery of DC.

  2. Amoxicillin Plus Metronidazole Therapy for Patients with Periodontitis and Type 2 Diabetes: A 2-year Randomized Controlled Trial.

    PubMed

    Tamashiro, N S; Duarte, P M; Miranda, T S; Maciel, S S; Figueiredo, L C; Faveri, M; Feres, M

    2016-07-01

    The aim of this study was to assess the changes occurring in subgingival biofilm composition and in the periodontal clinical parameters of subjects with periodontitis and type 2 diabetes mellitus (DM) treated by means of scaling and root planing (SRP) only or combined with systemic metronidazole (MTZ) and amoxicillin (AMX). Fifty-eight subjects were randomly assigned to receive SRP only (n = 29) or with MTZ (400 mg/thrice a day [TID]) and AMX (500 mg/TID) (n = 29) for 14 d. Six subgingival plaque samples/subject were analyzed by checkerboard DNA-DNA hybridization for 40 bacterial species at baseline and 3 mo, 1 y, and 2 y posttherapy. At 2 y posttherapy, the antibiotic-treated group harbored lower mean proportions (5.5%) of red complex pathogens than the control group (12.1%) (P < 0.05). The proportions of the Actinomyces species remained stable in the antibiotic group but showed a statistically significant reduction in the control group from 1 to 2 y in subjects achieving a low risk clinical profile for future disease progression (i.e., ≤4 sites with probing depth [PD] ≥5 mm). The test group also had a lower mean number of sites with PD ≥5 mm (3.5 ± 3.4) and a higher percentage of subjects reaching the low risk clinical profile (76%) than the control group (14.7 ± 13.1 and 22%, respectively) (P < 0.05) at 2 y posttreatment. MTZ + AMX intake was the only significant predictor of subjects achieving the low risk at 2 y (odds ratio, 20.9; P = 0.0000). In conclusion, the results of this study showed that the adjunctive use of MTZ + AMX improves the microbiological and clinical outcomes of SRP in the treatment of subjects with generalized chronic periodontitis and type 2 DM up to 2 y (ClinicalTrials.gov NCT02135952). PMID:27013640

  3. Isolate resistance of Blastocystis hominis to metronidazole.

    PubMed

    Haresh, K; Suresh, K; Khairul Anus, A; Saminathan, S

    1999-04-01

    Isolates of Blastocystis hominis from infected immigrant workers from Indonesia, Bangladesh and infected individuals from Singapore and Malaysia were assessed for growth pattern and degree of resistance to different concentrations of metronidazole. Viability of the cells was assessed using eosin-brillian cresyl blue which stained viable cells green and nonviable cells red. The Bangladeshi and Singaporean isolates were nonviable even at the lowest concentration of 0.01 mg/ml, whereas 40% of the initial inoculum of parasites from the Indonesian isolate at day one were still viable in cultures with 1.0 mg/ml metronidazole. The study shows that isolates of B. hominis of different geographical origin have different levels of resistance to metronidazole. The search for more effective drugs to eliminate th parasite appears inevitable, especially since surviving parasites from metronidazole cultures show greater ability to multiply in subcultures than controls. PMID:10357863

  4. Photocurable bioadhesive based on lactic acid.

    PubMed

    Marques, D S; Santos, J M C; Ferreira, P; Correia, T R; Correia, I J; Gil, M H; Baptista, C M S G

    2016-01-01

    Novel photocurable and low molecular weight oligomers based on l-lactic acid with proven interest to be used as bioadhesive were successfully manufactured. Preparation of lactic acid oligomers with methacrylic end functionalizations was carried out in the absence of catalyst or solvents by self-esterification in two reaction steps: telechelic lactic acid oligomerization with OH end groups and further functionalization with methacrylic anhydride. The final adhesive composition was achieved by the addition of a reported biocompatible photoinitiator (Irgacure® 2959). Preliminary in vitro biodegradability was investigated by hydrolytic degradation in PBS (pH=7.4) at 37 °C. The adhesion performance was evaluated using glued aminated substrates (gelatine pieces) subjected to pull-to-break test. Surface energy measured by contact angles is lower than the reported values of the skin and blood. The absence of cytoxicity was evaluated using human fibroblasts. A notable antimicrobial behaviour was observed using two bacterial models (Staphylococcus aureus and Escherichia coli). The cured material exhibited a strong thrombogenic character when placed in contact with blood, which can be predicted as a haemostatic effect for bleeding control. This novel material was subjected to an extensive characterization showing great potential for bioadhesive or other biomedical applications where biodegradable and biocompatible photocurable materials are required. PMID:26478350

  5. Stability of Metronidazole Suspensions.

    PubMed

    Donnelly, Ronald F; Ying, James

    2015-01-01

    Metronidazole is an antiprotozoal agent used in the treatment of bacterial and protozoal anaerobic infections. The objectives of this study were to develop concentrated metronidazole suspensions that are inexpensive and easy to prepare and determine the stability of these suspensions after storage in amber polyvinyl chloride bottles at room temperature (23°C) and under refrigeration (5°C). Metronidazole suspensions (50 mg/mL) were prepared from powder using Ora-Blend or simple syrup as the vehicles. Samples were collected in triplicate from each container on days 0, 7, 14, 28, 56, and 93. Samples were assayed using a high-performance liquid chromatography method that had been validated as stability indicating. Color, change in physical appearance, and pH were also monitored at each time interval. There was no apparent change in color or physical appearance. The pH values changed by less than 0.20 units over the 93 days. The stability of metronidazole suspensions compounded from United States Pharmacopeia powder using Ora-Blend or simple syrup and packaged in amber polyvinyl chloride bottles was determined to be 93 days when stored at either room temperature or under refrigeration. PMID:26714365

  6. Fabrication of a bioadhesive transdermal device from chitosan and hyaluronic acid for the controlled release of lidocaine.

    PubMed

    Anirudhan, T S; Nair, Syam S; Nair, Anoop S

    2016-11-01

    A novel efficient transdermal (TD) lidocaine (LD) delivery device based on chitosan (CS) and hyaluronic acid (HA) was successfully developed in the present investigation. CS was grafted with glycidyl methacrylate (GMA) and butyl methacrylate (BMA) to fabricate a versatile material with improved adhesion and mechanical properties. HA was hydrophobically modified by covalently conjugating 3-(dimethylamino)-1-propylamine (DMPA) to encapsulate poorly water soluble LD and was uniformly dispersed in modified CS matrix. The prepared materials were characterized through FTIR, NMR, XRD, SEM, TEM and tensile assay. The dispersion of amine functionalized HA (AHA) on modified CS matrix offered strong matrix - filler interaction, which improved the mechanical properties and drug retention behavior of the device. In vitro skin permeation study of LD was performed with modified Franz diffusion cell using rat skin and exhibited controlled release. The influence of storage time on release profile was investigated and demonstrated that after the initial burst, LD release profile of the device after 30 and 60days storage was identical to that of a device which was not stored. In vivo skin adhesion test and skin irritation assay in human subjects, water vapor permeability and environmental fitness test was performed to judge its application in biomedical field. All results displayed that the fabricated device is a potential candidate for TD LD administration to the systemic circulation. PMID:27516320

  7. Bioadhesive vaginal tablets containing spray dried microspheres loaded with clotrimazole for treatment of vaginal candidiasis.

    PubMed

    Gupta, Naresh Vishal; Natasha, Shirodker; Getyala, Anil; Bhat, Ramnath Sudeendra

    2013-09-01

    The aim of the present investigation was to prepare and evaluate novel bioadhesive vaginal tablets containing clotrimazole loaded microspheres in order to provide long-term therapeutic activity at the site of infection. Tablets were prepared by incorporating drug loaded microspheres and using bioadhesive polymers hydroxypropylmethylcellulose, sodium carboxymethylcellulose and Carbopol. Microspheres were prepared by the spray drying technique using Eudragit RS-100 and Eudragit RL-100. Microspheres were characterized by SEM, DSC, FTIR, particle size analysis and evaluated for percentage yield, drug loading, encapsulation efficiency and in vitro drug release. To achieve bioadhesion to the mucosal tissue, optimized microspheres were incorporated into bioadhesive tablets and were evaluated for in vitro drug release, in vitro and in vivo mucoadhesion. FTIR and DSC studies showed that no chemical interaction occurred between the drug and polymers. The sphericity factor indicated that the prepared microspheres were spherical. Formulation Mt6 indicated a controlled in vitro drug release and good bioadhesive strength. The in vivo images confirmed the bioadhesion and retention property of tablets up to 24 h. The results indicated that this drug delivery system can be explored for controlled intravaginal drug release.

  8. Evaluation of polyoxyethylene homopolymers for buccal bioadhesive drug delivery device formulations.

    PubMed

    Tiwari, D; Goldman, D; Sause, R; Madan, P L

    1999-01-01

    Our objective was to evaluate the application of polyoxyethylene homopolymers in buccal bioadhesive drug (BBD) delivery device formulations. The bioadhesive strength of four different molecular weight (MW) polyoxyethylene polymers was measured by Instron tensile tester using glass plate and bovine sublingual tissue as substrate surfaces. Several BBD device formulations containing polyoxyethylene polymer (MW 7,000,000) were prepared by direct compression and compression molding processes. The prepared BBD devices were evaluated for their elasticity, in vitro adhesion and drug release characteristics. The in vivo bioadhesion characteristics of a placebo compression molded device were examined in 3 adult healthy male beagle dogs. The bioadhesive strength of polyoxyethylene polymers appeared to be directly related to their molecular weights. When bovine sublingual mucosa or a glass plate was used as model mucosal substrate surface, the rank order of bioadhesive strength of different molecular weight polyoxyethylene polymers was similar. The bioadhesive strength of devices prepared by the compression molding process was greater than those prepared by direct compression, but the kinetics of drug release were independent of the process used for the preparation of the devices. The drug release and the bioadhesive strength of the similarly prepared device formulations appeared to be dependent on the drug:polymer ratios. The elasticity of the BBD devices prepared by compression molding was improved by the inclusion of polyisobutylene polymer in the formulations. When adhered to the oral cavity of the dogs, the compression molded placebo BBD device exhibited adhesion for at least 4 hours and appeared to show no signs of local irritation. In conclusion, BBD devices containing polyoxyethylene polymer (MW 7,000,000) can be prepared by direct compression or compression molding process in order to provide controlled drug release to the oral cavity while maintaining appropriate

  9. Bioadhesive Mini-Tablets for Vaginal Drug Delivery

    PubMed Central

    Hiorth, Marianne; Nilsen, Susanne; Tho, Ingunn

    2014-01-01

    Different non-ionic cellulose ethers (methyl cellulose, MC; hydroxyethyl cellulose, HEC; hydroxypropyl cellulose, HPC; hydroxypropylmethyl cellulose, HPMC) and microcrystalline cellulose (MCC) were investigated as matrix formers for preparation of mini-tablets targeting vaginal drug delivery. Hexyl aminolevulinat hydrochloridum (HAL) was used as a model drug. The mini-tablets were characterized with respect to their mechanical strength, bioadhesion towards cow vaginal tissue in two independent tests (rotating cylinder test, detachment test using texture analyzer), and dissolution rate in two media mimicking the pH levels of fertile, healthy and post-menopausal women (vaginal fluid simulant pH 4.5, phosphate buffer pH 6.8). Mini-tablets with a matrix of either HPMC or HPC were found to possess adequate mechanical strength, superior bioadhesive behavior towards vaginal tissue, and pH independent controlled release of the model drug, suggesting that both systems would be suited for the treatment of women regardless of age, i.e., respective of their vaginal pH levels. Bioadhesive mini-tablets offer a potential for improved residence time in the vaginal cavity targeting contact with mucosal tissue and prolonged release of the drug. PMID:25166286

  10. Quantifying the bioadhesive properties of surface-modified polyurethane-urea nanoparticles in the vascular network.

    PubMed

    Melgar-Lesmes, Pedro; Morral-Ruíz, Genoveva; Solans, Conxita; García-Celma, María José

    2014-06-01

    Nanomedicine research is currently requiring new standard methods to quantify the biocompatibility and bioadhesivity of emerging biomaterials designed to be used in contact with blood or soft tissues. In this study, we used biotinylated polyurethane-urea nanoparticles as a model to examine the applicabitility of an adapted hemagglutination assay to quantify the bioadhesive potential of these nanoparticles to red blood cells and, in turn, to extrapolate this data to vascular endothelial cells. We demonstrated that biotinylated nanoparticles adsorb to human erythrocytes and preferentially gather in erythrocyte contact areas. Moreover, these nanoparticles promoted a higher percentage of pig and human erythrocyte agglutination than naked polyurethane-urea nanoparticles in a biotin concentration-dependent manner. Conversely, pegylated nanoparticles were used as a negative control of the technique thus showing decreasing hemagglutination values as compared to naked nanoparticles until a minimum threshold. Furthermore, hemagglutination assay demonstrated an excellent positive correlation with bioadhesion quantification in human endothelial cells and the endothelial layer of pig aorta thus validating the hemagglutination assay described here as a useful method for predicting nanoparticle bioadhesivity to vascular endothelium. Therefore, the methodology described here is a versatile and straightforward method that allows evaluating the bioadhesive features of surface-modified polyurethane-urea nanoparticles in contact with blood and the vascular network and appears as a powerful tool to better design any drug delivery systems or implantable devices for biomedical applications.

  11. 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

  12. Topical metronidazole combination therapy in the clinical management of rosacea.

    PubMed

    Del Rosso, James Q; Bikowski, Joseph

    2005-01-01

    Metronidazole was the first topical agent approved by the U.S. Food and Drug Administration for the treatment of rosacea. Several controlled studies have confirmed the efficacy and safety of topical metronidazole 0.75% gel, lotion and cream and 1% cream for rosacea. At present, little data exists regarding the use of combination topical therapy in rosacea management, although anecdotal evidence and preliminary studies suggest at least some additive benefit when topical metronidazole is used in combination with sulfacetamide 10% /sulfur 5%. In this paper, the results of observational experience evaluating topical metronidazole 0.75% gel used in combination with other topical rosacea therapies and/or subantimicrobial dose doxycycline are reported.

  13. Injectable bioadhesive hydrogels with innate antibacterial properties

    NASA Astrophysics Data System (ADS)

    Giano, Michael C.; Ibrahim, Zuhaib; Medina, Scott H.; Sarhane, Karim A.; Christensen, Joani M.; Yamada, Yuji; Brandacher, Gerald; Schneider, Joel P.

    2014-06-01

    Surgical site infections cause significant postoperative morbidity and increased healthcare costs. Bioadhesives used to fill surgical voids and support wound healing are typically devoid of antibacterial activity. Here we report novel syringe-injectable bioadhesive hydrogels with inherent antibacterial properties prepared from mixing polydextran aldehyde and branched polyethylenimine. These adhesives kill both Gram-negative and Gram-positive bacteria, while sparing human erythrocytes. An optimal composition of 2.5 wt% oxidized dextran and 6.9 wt% polyethylenimine sets within seconds forming a mechanically rigid (~\

  14. Optical Spectroscopy of Marine Bioadhesive Interfaces

    NASA Astrophysics Data System (ADS)

    Barlow, Daniel E.; Wahl, Kathryn J.

    2012-07-01

    Marine organisms have evolved extraordinarily effective adhesives that cure underwater and resist degradation. These underwater adhesives differ dramatically in structure and function and are composed of multiple proteins assembled into functional composites. The processes by which these bioadhesives cure—conformational changes, dehydration, polymerization, and cross-linking—are challenging to quantify because they occur not only underwater but also in a buried interface between the substrate and the organism. In this review, we highlight interfacial optical spectroscopy approaches that can reveal the biochemical processes and structure of marine bioadhesives, with particular emphasis on macrofoulers such as barnacles and mussels.

  15. Optimization of Metronidazole Emulgel

    PubMed Central

    Rao, Monica; Sukre, Girish; Aghav, Sheetal; Kumar, Manmeet

    2013-01-01

    The purpose of the present study was to develop and optimize the emulgel system for MTZ (Metronidazole), a poorly water soluble drug. The pseudoternary phase diagrams were developed for various microemulsion formulations composed of Capmul 908 P, Acconon MC8-2, and propylene glycol. The emulgel was optimized using a three-factor, two-level factorial design, the independent variables selected were Capmul 908 P, and surfactant mixture (Acconon MC8-2 and gelling agent), and the dependent variables (responses) were a cumulative amount of drug permeated across the dialysis membrane in 24 h (Y1) and spreadability (Y2). Mathematical equations and response surface plots were used to relate the dependent and independent variables. The regression equations were generated for responses Y1 and Y2. The statistical validity of the polynomials was established, and optimized formulation factors were selected. Validation of the optimization study with 3 confirmatory runs indicated a high degree of prognostic ability of response surface methodology. Emulgel system of MTZ was developed and optimized using 23 factorial design and could provide an effective treatment against topical infections. PMID:26555982

  16. Formulation, In Vitro and In Vivo Pharmacokinetics of Anti-HIV Vaginal Bioadhesive Gel

    PubMed Central

    Chatterjee, A; Bhowmik, B B; Thakur, Y S

    2011-01-01

    Inexpensive and female-controlled pre-exposure prophylaxis strategies to prevent mucosal transmission of the virus, is urgently needed with the rising prevalence of human immunodeficiency virus (HIV-1 and HIV2) infections in women. Zidovudine-loaded bioadhesive vaginal gel may become one of the very useful strategies, as it can be used not only for controlled release but also for enhancing bioavailability. Drug delivery through vaginal gel is a promising area for continued research with the aim of achieving controlled release with enhanced bioavailability over longer periods of time. The aim of the study was to develop a newer prolong releasing Zidovudine (AZT) bioadhesive vaginal gel to treat HIV infections with increased patient convenience. AZT-loaded bioadhesive vaginal gel was prepared successfully by using cold mechanical method. F3 formulation containing carbopol–HPMC (1:3) was selected and evaluated in order to achieve objectives of this study. In vitro drug release study of F3 showed in 24 h drug released following case I Fickian (n ≤ 0.5) transport mechanism, and in vivo drug release was found much better (Tmax), (Cmax), and bioavailability (F) comparison with oral pour drug solution. It was also showed good extrudability, spreadability, and bioadhesive strength. A generalized protocol, for the further research, in this area will surely expected to yield significant outcome with improved drug delivery system. PMID:21731351

  17. Dual-crosslinked oxidized, methacrylated alginate/PEG hydrogels for bioadhesive applications

    PubMed Central

    Jeon, Oju; Samorezov, Julia E.; Alsberg, Eben

    2013-01-01

    A degradable, cytocompatible bioadhesive can facilitate surgical procedures and minimize patient pain and postsurgical complications. In this study, a bioadhesive hydrogel system based on oxidized, methacrylated alginate/8-arm poly(ethylene glycol) amine (OMA/PEG) has been developed, and the bioadhesive characteristics of the crosslinked OMA/PEG hydrogels are evaluated. Here, we demonstrate that the swelling behavior, degradation profiles, and storage moduli of crosslinked OMA/PEG hydrogels are tunable by varying the degree of alginate oxidation. The crosslinked OMA/PEG hydrogels exhibit cytocompatibility when cultured with human bone marrow-derived mesenchymal stem cells. In addition, the adhesion strength of these hydrogels, controllable by varying the alginate oxidation level and measured using a porcine skin model, is superior to commercially available fibrin glue. This OMA/PEG hydrogel system with controllable biodegradation and mechanical properties and adhesion strength may be a promising bioadhesive for clinical use in biomedical applications, such as drug delivery, wound closure and healing, biomedical device implantation, and tissue engineering. PMID:24035886

  18. Tuning model drug release and soft-tissue bioadhesion of polyester films by plasma post-treatment.

    PubMed

    Mogal, Vishal T; Yin, Chaw Su; O'Rorke, Richard; Boujday, Souhir; Méthivier, Christophe; Venkatraman, Subbu S; Steele, Terry W J

    2014-04-23

    Plasma treatments are investigated as a post-production method of tuning drug release and bioadhesion of poly(lactic-co-glycolic acid) (PLGA) thin films. PLGA films were treated under varying conditions by controlling gas flow rate, composition, treatment time, and radio frequency (RF) power. In vitro release of the drug-like molecule fluorescein diacetate (FDAc) from plasma-treated PLGA was tunable by controlling RF power; an increase of 65% cumulative release is reported compared to controls. Bioadhesion was sensitive to RF power and treatment time, assessed using ex vivo shear-stress tests with wetted swine aorta. We report a maximum bioadhesion ∼6-fold that of controls and 5-fold that of DOPA-based mussel adhesives tested to swine skin.1 The novelty of this post-treatment is the activation of a hydrophobic polyester film for bioadhesion, which can be quenched, while simultaneously tuning drug-release kinetics. This exemplifies the promise of plasma post-treatment for in-clinic bioadhesive activation, along with technological advancements, i.e., atmospheric plasma and hand-held "plasma pencils". PMID:24666261

  19. Moxifloxacin in situ gelling microparticles–bioadhesive delivery system

    PubMed Central

    Guo, Qiongyu; Aly, Ahmed; Schein, Oliver; Trexler, Morgana M.; Elisseeff, Jennifer H.

    2012-01-01

    Antibiotic use for ocular treatments has been largely limited by poor local bioavailability with conventional eyedrops formulations. Here, we developed a controlled delivery system composed of moxifloxacin-loaded poly(lactic-co-glycolic acid) (PLGA) microparticles encapsulated in a chondroitin sulfate-based, two-component bioadhesive hydrogel. Using a simple and fast electrohydrodynamic spray drying (electrospraying) technique, surfactant-free moxifloxacin-loaded microparticles were fabricated with diameters on the order of 1 μm. A mixed solvent system of methanol/dichloromethane (MeOH/DCM) was employed to prepare the microparticles for the electrospraying processing. Extended release of moxifloxacin using a series of MeOH/DCM mixed solvents was accomplished over 10 days with release concentrations higher than the minimum inhibitory concentration (MIC). In contrast, moxifloxacin loaded directly in hydrogels was released rapidly within 24 h. We observed a decrease of the drug release rate from the microparticles when using an increased percentage of methanol in the mixed solvent from 10% to 30% (v/v), which can be explained by the mixed solvent system providing a driving force to form a gradient of the drug concentrations inside the microparticles. In addition, the delivery system developed in this study, which incorporates a bioadhesive to localize drug release by in situ gelling, may potentially integrate antibiotic prophylaxis and wound healing in the eye. PMID:25755996

  20. Moxifloxacin in situ gelling microparticles-bioadhesive delivery system.

    PubMed

    Guo, Qiongyu; Aly, Ahmed; Schein, Oliver; Trexler, Morgana M; Elisseeff, Jennifer H

    2012-01-01

    Antibiotic use for ocular treatments has been largely limited by poor local bioavailability with conventional eyedrops formulations. Here, we developed a controlled delivery system composed of moxifloxacin-loaded poly(lactic-co-glycolic acid) (PLGA) microparticles encapsulated in a chondroitin sulfate-based, two-component bioadhesive hydrogel. Using a simple and fast electrohydrodynamic spray drying (electrospraying) technique, surfactant-free moxifloxacin-loaded microparticles were fabricated with diameters on the order of 1 μm. A mixed solvent system of methanol/dichloromethane (MeOH/DCM) was employed to prepare the microparticles for the electrospraying processing. Extended release of moxifloxacin using a series of MeOH/DCM mixed solvents was accomplished over 10 days with release concentrations higher than the minimum inhibitory concentration (MIC). In contrast, moxifloxacin loaded directly in hydrogels was released rapidly within 24 h. We observed a decrease of the drug release rate from the microparticles when using an increased percentage of methanol in the mixed solvent from 10% to 30% (v/v), which can be explained by the mixed solvent system providing a driving force to form a gradient of the drug concentrations inside the microparticles. In addition, the delivery system developed in this study, which incorporates a bioadhesive to localize drug release by in situ gelling, may potentially integrate antibiotic prophylaxis and wound healing in the eye. PMID:25755996

  1. Metronidazole and the immune system.

    PubMed

    Shakir, L; Javeed, A; Ashraf, M; Riaz, A

    2011-06-01

    Metronidazole (MTZ) is a nitroimidazole antibiotic used mainly for the treatment of infections caused by susceptible organisms, particularly anaerobic bacteria and protozoa. Distinct from its antibiotic, amoebicidal, and antiprotozoal effects, MTZ displays immunopharmacological behaviour. This review outlines multiple effects of MTZ on different aspects of immunity, including innate and acquired immunity, and also highlights the immunopharmacological behaviour of MTZ in terms of its relevance to inflammation, delayed type hypersensitivity (DTH) and graft versus host disease (GVHD).

  2. 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.

  3. Formulation and Characterization of Cetylpyridinium Chloride Bioadhesive Tablets

    PubMed Central

    Akbari, Jafar; Saeedi, Majid; Morteza-Semnani, Katayoun; Kelidari, Hamidreza; Lashkari, Maryam

    2014-01-01

    Purpose: Bioadhesive polymers play an important role in biomedical and drug delivery applications. The aim of this study is to develop a sustained- release tablet for local application of Cetylpyridinium Chloride (CPC). This delivery system would supply the drug at an effective level for a long period of time, and thereby overcome the problem of the short retention time of CPC and could be used for buccal delivery as a topical anti-infective agent. Methods: CPC bioadhesive tablets were directly prepared using 7 mm flat-faced punches on a hydraulic press. The materials for each tablet were weighted, introduced into the die and compacted at constant compression pressure. The dissolution tests were performed to the rotation paddle method and the bioadhesive strength of the tablets were measured. Results: The results showed that as the concentration of polymer increased, the drug release rate was decreased. Also the type and ratio of polymers altered the release kinetic of Cetylpyridinium Chloride from investigated tablets. The bioadhesion strength increased with increasing the concentration of polymer and maximum bioadhesion strength was observed with HPMC K100M. Conclusion: The selected formulation of CPC bioadhesive tablet can be used as a suitable preparation for continuous release of CPC with appropriate bioadhesion strength. PMID:25436196

  4. Evaluation of bioadhesive polymers as delivery systems for nose to brain delivery: in vitro characterisation studies.

    PubMed

    Charlton, S T; Davis, S S; Illum, L

    2007-04-01

    There is an increasing need for nasal drug delivery systems that could improve the efficiency of the direct nose to brain pathway especially for drugs for treatment of central nervous system disorders. Novel approaches that are able to combine active targeting of a formulation to the olfactory region with controlled release bioadhesive characteristics, for maintaining the drug on the absorption site are suggested. If necessary an absorption enhancer could be incorporated. Low methylated pectins have been shown to gel and be retained in the nasal cavity after deposition. Chitosan is known to be bioadhesive and also to work as an absorption enhancer. Consequently, two types of pectins, LM-5 and LM-12, together with chitosan G210, were selected for characterisation in terms of molecular weight, gelling ability and viscosity. Furthermore, studies on the in vitro release of model drugs from candidate formulations and the transport of drugs across MDCK1 cell monolayers in the presence of pectin and chitosan were also performed. Bioadhesive formulations providing controlled release with increased or decreased epithelial transport were developed. Due to their promising characteristics 3% LM-5, 1% LM-12 pectin and 1% chitosan G210 formulations were selected for further biological evaluation in animal models.

  5. 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.

  6. 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.

  7. A Sunblock Based On Bioadhesive Nanoparticles

    PubMed Central

    Deng, Yang; Ediriwickrema, Asiri; Yang, Fan; Lewis, Julia; Girardi, Michael

    2015-01-01

    The majority of commercial sunblock preparations utilize organic or inorganic ultraviolet (UV) filters. Despite protecting against cutaneous phototoxicity, direct cellular exposure to UV filters has raised a variety of health concerns. Here, we show that the encapsulation of padimate O (PO) - a model UV filter - in bioadhesive nanoparticles (BNPs) prevents epidermal cellular exposure to UV filters while enhancing UV protection. BNPs are readily suspended in water, facilitate adherence to the stratum corneum without subsequent intra-epidermal or follicular penetration, and their interaction with skin is water-resistant yet the particles can be removed via active towel drying. Although the sunblock based on BNPs contained less than 5 wt% of the UV-filter concentration found in commercial standards, the anti-UV effect was comparable when tested in two murine models. Moreover, the BNP-based sunblock significantly reduced double-stranded DNA breaks when compared to a commercial sunscreen formulation. PMID:26413985

  8. A sunblock based on bioadhesive nanoparticles

    NASA Astrophysics Data System (ADS)

    Deng, Yang; Ediriwickrema, Asiri; Yang, Fan; Lewis, Julia; Girardi, Michael; Saltzman, W. Mark

    2015-12-01

    The majority of commercial sunblock preparations use organic or inorganic ultraviolet (UV) filters. Despite protecting against cutaneous phototoxicity, direct cellular exposure to UV filters has raised a variety of health concerns. Here, we show that the encapsulation of padimate O (PO)--a model UV filter--in bioadhesive nanoparticles (BNPs) prevents epidermal cellular exposure to UV filters while enhancing UV protection. BNPs are readily suspended in water, facilitate adherence to the stratum corneum without subsequent intra-epidermal or follicular penetration, and their interaction with skin is water resistant yet the particles can be removed via active towel drying. Although the sunblock based on BNPs contained less than 5 wt% of the UV-filter concentration found in commercial standards, the anti-UV effect was comparable when tested in two murine models. Moreover, the BNP-based sunblock significantly reduced double-stranded DNA breaks when compared with a commercial sunscreen formulation.

  9. 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

  10. Effect of bioadhesion on initial in vitro buoyancy of effervescent floating matrix tablets of ciprofloxacin HCL

    PubMed Central

    Negi, Jeetendra Singh; Trivedi, Abhinav; Khanduri, Praveen; Negi, Vandana; Kasliwal, Nikhil

    2011-01-01

    The purpose of this study was to investigate effect of bioadhesion on the initial in vitro buoyancy behaviour of effervescent matrix tablets of ciprofloxacin HCl (CIPRO). Tablets were prepared by direct compression using HPMC K4M and Carbopol 971P as hydrophilic-controlled release polymers, sodium bicarbonate (NaHCO3) as gas-generating agent, polyplasdone XL, Explotab and Ac-Di-Sol as swelling agents. Tablets were evaluated for normal and modified initial in vitro floating behavior, floating duration, swelling behavior and in vitro drug release studies. A modified buoyancy lag time for tablets was determined in order to include the effect of bioadhesion on initial buoyancy. The initial buoyancy was found depended on bioadhesion ability of tablets. The lowest modified buoyancy lag time of 20 seconds was obtained for Formulation F7 having both NaHCO3 and polyplasdone XL. The floating duration was also found dependent on concentration of NaHCO3 and swelling agents. The drug release of F7 was also sustained up to 12-hr duration with anomalous drug transport mechanism. PMID:22171304

  11. 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.

  12. Muco-bioadhesive containing ginger officinale extract in the management of recurrent aphthous stomatitis: A randomized clinical study

    PubMed Central

    Haghpanah, Parya; Moghadamnia, Ali Akbar; Zarghami, Amin; Motallebnejad, Mina

    2015-01-01

    Background: Recurrent aphthous stomatitis (RAS) is the most common oral mucosal lesions in the general population. Various treatment modalities have been used; but no specific therapy proved to be definitive. Ginger Officinale (ginger) indicated to have anti-inflammatory properties in herbal medicine. Thus, this study aimed to evaluate the efficacy of ginger containing bioadhesive in the treatment of aphthous ulcers. Methods: In this randomized double-blind placebo-controlled trial, 15 patients were enrolled. The clinical efficacy of the mucoadhessive on pain, inflammatory zone and ulcer's diameter in the test period was compared with that of the base treatment and no treatment periods during 10 days of study. Results: Significant reduction in pain was observed on day 5 between placebo (using base bioadhesives) and without treatment periods at the first phase of the study (4.53 vs. 3.27; P=0.038. ( Reduction in inflamed halo diameters was significant on day 1 between without treatment and ginger containing bioadhesives )46.73 vs 28.67; P=0.044). Other variables such as the diameter of ulcers did not indicate any significant differences in both periods. Conclusion: This study indicated that ginger bioadhesive is capable to relieve pain of RAS. However, its efficacy on ulcer diameter, inflamed halo and healing time was not significantly different compared to the results of the placebo received period. PMID:26221489

  13. Tunable bioadhesive copolymer hydrogels of thermoresponsive poly(N-isopropyl acrylamide) containing zwitterionic polysulfobetaine.

    PubMed

    Chang, Yung; Yandi, Wetra; Chen, Wen-Yih; Shih, Yu-Ju; Yang, Chang-Chung; Chang, Yu; Ling, Qing-Dong; Higuchi, Akon

    2010-04-12

    This work describes a novel tunable bioadhesive hydrogel of thermoresponsive N-isopropylacrylamide (NIPAAm) containing zwitterionic sulfobetaine methacrylate (SBMA). This novel hydrogel highly regulates general bioadhesive foulants through the adsorption of plasma proteins, the adhesion of human platelets and cells, and the attachment of bacteria. In this investigation, nonionic hydrogels of polyNIPAAm, zwitterionic hydrogels of polySBMA, and three copolymeric hydrogels of NIPAAm and SBMA (poly(NIPAAm-co-SBMA)) were prepared. The copolymeric hydrogels exhibited controllable temperature-dependent swelling behaviors and showed stimuli-responsive phase characteristics in the presence of salts. The interactions of these hydrogels with biomolecules and microorganisms were demonstrated by protein adsorption, cell adhesion, and bacterial attachment, which allowed us to evaluate their bioadhesive properties. An enzyme-linked immunosorbent assay (ELISA) with monoclonal antibodies was used to measure different plasma protein adsorptions on the prepared hydrogel surfaces. At a physiological temperature, the high content of the nonionic polyNIPAAm in poly(NIPAAm-co-SBMA) hydrogel exhibits a high protein adsorption due to the interfacial exposure of polyNIPAAm-rich hydrophobic domains. A relatively high content of polySBMA in poly(NIPAAm-co-SBMA) hydrogel exhibits reduced amounts of protein adsorption due to the interfacial hydration of polySBMA-rich hydrophilic segments. The attachment of platelets and the spreading of cells were only observed on polyNIPAAm-rich hydrogel surfaces. Interestingly, the incorporation of zwitterionic SBMA units into the polyNIPAAm gels was found to accelerate the hydration of the cell-cultured surfaces and resulted in more rapid cell detachment. Such copolymer gel surface was shown to be potentially useful for triggered cell detachment. In addition, the interactions of hydrogels with bacteria were also evaluated. The polySBMA-rich hydrogels

  14. An update on the role of topical metronidazole in rosacea.

    PubMed

    Zip, C

    2006-03-01

    Topical metronidazole (Noritate 1% Cream, Dermik; MetroCream 0.75% Cream, MetroLotion 0.75% Lotion, Metrogel 0.75% and 1% Topical Gel, Galderma) has been used for the treatment of rosacea for over 30 years. Several placebo-controlled trials have demonstrated its effectiveness in the treatment of moderate-to-severe rosacea. It is also effective in preventing relapses of disease and is well tolerated by most patients. A growing number of formulations are available.

  15. Effect of HPMC and mannitol on drug release and bioadhesion behavior of buccal discs of buspirone hydrochloride: In-vitro and in-vivo pharmacokinetic studies

    PubMed Central

    Jaipal, A.; Pandey, M.M.; Charde, S.Y.; Raut, P.P.; Prasanth, K.V.; Prasad, R.G.

    2014-01-01

    Delivery of orally compromised therapeutic drug molecules to the systemic circulation via buccal route has gained a significant interest in recent past. Bioadhesive polymers play a major role in designing such buccal dosage forms, as they help in adhesion of designed delivery system to mucosal membrane and also prolong release of drug from delivery system. In the present study, HPMC (release retarding polymer) and mannitol (diluent and pore former) were used to prepare bioadhesive and controlled release buccal discs of buspirone hydrochloride (BS) by direct compression method. Compatibility of BS with various excipients used during the study was assessed using DSC and FTIR techniques. Effect of mannitol and HPMC on drug release and bioadhesive strength was studied using a 32 factorial design. The drug release rate from delivery system decreased with increasing levels of HPMC in formulations. However, bioadhesive strength of formulations increased with increasing proportion of HPMC in buccal discs. Increased levels of mannitol resulted in faster rate of drug release and rapid in vitro uptake of water due to the formation of channels in the matrix. Pharmacokinetic studies of designed bioadhesive buccal discs in rabbits demonstrated a 10-fold increase in bioavailability in comparison with oral bioavailability of buspirone reported. PMID:26106280

  16. Effect of HPMC and mannitol on drug release and bioadhesion behavior of buccal discs of buspirone hydrochloride: In-vitro and in-vivo pharmacokinetic studies.

    PubMed

    Jaipal, A; Pandey, M M; Charde, S Y; Raut, P P; Prasanth, K V; Prasad, R G

    2015-07-01

    Delivery of orally compromised therapeutic drug molecules to the systemic circulation via buccal route has gained a significant interest in recent past. Bioadhesive polymers play a major role in designing such buccal dosage forms, as they help in adhesion of designed delivery system to mucosal membrane and also prolong release of drug from delivery system. In the present study, HPMC (release retarding polymer) and mannitol (diluent and pore former) were used to prepare bioadhesive and controlled release buccal discs of buspirone hydrochloride (BS) by direct compression method. Compatibility of BS with various excipients used during the study was assessed using DSC and FTIR techniques. Effect of mannitol and HPMC on drug release and bioadhesive strength was studied using a 3(2) factorial design. The drug release rate from delivery system decreased with increasing levels of HPMC in formulations. However, bioadhesive strength of formulations increased with increasing proportion of HPMC in buccal discs. Increased levels of mannitol resulted in faster rate of drug release and rapid in vitro uptake of water due to the formation of channels in the matrix. Pharmacokinetic studies of designed bioadhesive buccal discs in rabbits demonstrated a 10-fold increase in bioavailability in comparison with oral bioavailability of buspirone reported. PMID:26106280

  17. 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

  18. Molecular biology approaches in bioadhesion research

    PubMed Central

    Rodrigues, Marcelo; Lengerer, Birgit; Ostermann, Thomas

    2014-01-01

    Summary The use of molecular biology tools in the field of bioadhesion is still in its infancy. For new research groups who are considering taking a molecular approach, the techniques presented here are essential to unravelling the sequence of a gene, its expression and its biological function. Here we provide an outline for addressing adhesion-related genes in diverse organisms. We show how to gradually narrow down the number of candidate transcripts that are involved in adhesion by (1) generating a transcriptome and a differentially expressed cDNA list enriched for adhesion-related transcripts, (2) setting up a BLAST search facility, (3) perform an in situ hybridization screen, and (4) functional analyses of selected genes by using RNA interference knock-down. Furthermore, latest developments in genome-editing are presented as new tools to study gene function. By using this iterative multi-technologies approach, the identification, isolation, expression and function of adhesion-related genes can be studied in most organisms. These tools will improve our understanding of the diversity of molecules used for adhesion in different organisms and these findings will help to develop innovative bio-inspired adhesives. PMID:25161834

  19. Role of metronidazole resistance in therapy of Helicobacter pylori infections.

    PubMed Central

    Rautelin, H; Seppälä, K; Renkonen, O V; Vainio, U; Kosunen, T U

    1992-01-01

    Susceptibility to metronidazole was determined by disk diffusion tests for 559 strains of Helicobacter pylori isolated from patients. The overall metronidazole resistance was 26%. In males metronidazole-resistant strains made 18% of all H. pylori strains, and in females the corresponding figure was 40% (P less than 0.001). MICs of metronidazole were determined for H. pylori strains from 86 patients undertaking triple therapy, i.e., treatment with colloidal bismuth subcitrate, amoxicillin, and metronidazole. Of the nonresponders who remained culture positive despite the therapy, 69% had strains with metronidazole MICs of greater than or equal to 32 micrograms/ml before the therapy, and all nonresponders had metronidazole-resistant strains after the therapy. Metronidazole resistance was, however, also found in 27% of responders before therapy. To find whether the MICs of metronidazole for H. pylori strains remained constant for longer periods, consecutive isolates sampled several years apart from the same patients were tested in parallel and no changes in the MICs were found. H. pylori was successfully eradicated by the triple therapy from 91% of patients with metronidazole-susceptible pretreatment strains and from 63% of patients with metronidazole-resistant strains before the therapy (P less than 0.01). Although resistance to metronidazole has a significant role in treatment failures in H. pylori infections, high eradication rates can be achieved with the use of the present triple therapy even in populations with a high overall metronidazole resistance rate. PMID:1590683

  20. Acute Onset Sensory Polyneuropathy Due to Metronidazole Therapy.

    PubMed

    Singh, Jitendra; Atam, Virendra; Dinkar, Anju

    2015-09-01

    Metronidazole is associated with numerous neurologic complications, including peripheral neuropathy particularly in patients; those are on high doses of metronidazole for prolonged period. We hereby report a case of liver abscess that developed sensory polyneuropathy following 11 days of metronidazole therapy at low cumulative dose. PMID:27608880

  1. Metronidazole: effect on radiosensitivity of tumor and normal tissues in mice.

    PubMed

    Stone, H B; Withers, H R

    1975-11-01

    Local control of a mammary carcinoma in air-breathing C3H mice was enhanced by giving metronidazole before radiotherapy; When 0.5-1.0 mg metronidazole/g body weight was given ip 10 minutes before irradiation, the dose required for local control of 50% of the tumors (TCD50) was reduced by a factor of 1.37-1.38. The TCD50 was reduced by a factor of 1.48-1.50 when tumors were irradiated 30-60 minutes after 1.0 mg/g. Metronidazole alone, at a dose of 1.0 mg/g, only slightly inhibited tumor growth. The acute skin response of the leg, as determined by the radiation dose required to produce complete moist desquamation in 50% of the animals (DD50), was enhanced by a factor of 1.26 when mice were irradiated 10 minutes after a dose of 1.0 mg metronidazole/g. Clonogenic cells in the jejunal epithelium were not sensitized after metronidazole administration in either air-breathing mice or those irradiated in O2 30 pounds per square inch, but the drug appeared to exert a slight protective effect at higher doses of radiation.

  2. 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.

  3. 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. PMID:25655488

  4. Efficacy and Safety of Ceftazidime-Avibactam Plus Metronidazole Versus Meropenem in the Treatment of Complicated Intra-abdominal Infection: Results From a Randomized, Controlled, Double-Blind, Phase 3 Program

    PubMed Central

    Mazuski, John E.; Gasink, Leanne B.; Armstrong, Jon; Broadhurst, Helen; Stone, Greg G.; Rank, Douglas; Llorens, Lily; Newell, Paul; Pachl, Jan

    2016-01-01

    Background. When combined with ceftazidime, the novel non–β-lactam β-lactamase inhibitor avibactam provides a carbapenem alternative against multidrug-resistant infections. Efficacy and safety of ceftazidime-avibactam plus metronidazole were compared with meropenem in 1066 men and women with complicated intra-abdominal infections from 2 identical, randomized, double-blind phase 3 studies (NCT01499290 and NCT01500239). Methods. The primary end point was clinical cure at test-of-cure visit 28–35 days after randomization, assessed by noninferiority of ceftazidime-avibactam plus metronidazole to meropenem in the microbiologically modified intention-to-treat (mMITT) population (in accordance with US Food and Drug Administration guidance), and the modified intention-to-treat and clinically evaluable populations (European Medicines Agency guidance). Noninferiority was considered met if the lower limit of the 95% confidence interval for between-group difference was greater than the prespecified noninferiority margin of −12.5%. Results. Ceftazidime-avibactam plus metronidazole was noninferior to meropenem across all primary analysis populations. Clinical cure rates with ceftazidime-avibactam plus metronidazole and meropenem, respectively, were as follows: mMITT population, 81.6% and 85.1% (between-group difference, −3.5%; 95% confidence interval −8.64 to 1.58); modified intention-to-treat, 82.5% and 84.9% (−2.4%; −6.90 to 2.10); and clinically evaluable, 91.7% and 92.5% (−0.8%; −4.61 to 2.89). The clinical cure rate with ceftazidime-avibactam plus metronidazole for ceftazidime-resistant infections was comparable to that with meropenem (mMITT population, 83.0% and 85.9%, respectively) and similar to the regimen's own efficacy against ceftazidime-susceptible infections (82.0%). Adverse events were similar between groups. Conclusions. Ceftazidime-avibactam plus metronidazole was noninferior to meropenem in the treatment of complicated intra

  5. 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

  6. Bioadhesive drug delivery systems. I. Characterisation of mucoadhesive properties of systems based on glyceryl mono-oleate and glyceryl monolinoleate.

    PubMed

    Nielsen, L S; Schubert, L; Hansen, J

    1998-07-01

    A group of fatty acid esters capable of forming liquid crystals has been identified as a new class of potential bioadhesive substances. The liquid crystals may act as a controlled release system. The experimental work was focused on the monoglycerides, glyceryl mono-oleate (GMO) and glyceryl monolinoleate (GML). The mucoadhesive properties of GMO and GML were demonstrated in vitro by a 'flushing' bioadhesion test system and a tensiometric method. The flushing system was validated with GMO. Mucoadhesion is influenced by the drug and excipient added, their concentrations, and the ability to form especially the cubic phase. It has been shown that the cubic phase is mucoadhesive when formed on wet mucosa, such as rabbit jejunum, and that drug added to the precursor formulation is incorporated in the cubic phase formed. Tensiometric measurements have shown that the unswollen monoglycerides have the greatest mucoadhesion, followed by the partly swollen lamellar phase and the fully swollen cubic phase. The values found for the work of adhesion were in the range 0.007-0.048 mJcm-2. The mechanism of mucoadhesion is unspecific and probably involves dehydration of the mucosa. The cubic phase of GMO and GML may be an interesting candidate for a bioadhesive drug delivery system.

  7. An atomic force microscopy investigation of bioadhesive polymer adsorption onto human buccal cells.

    PubMed

    Patel, D; Smith, J R; Smith, A W; Grist, N; Barnett, P; Smart, J D

    2000-05-10

    Atomic force microscopy (AFM) was used to examine the buccal cell surface in order to image the presence of adsorbed bioadhesive polymers identified from previous work. Isotonic saline solution (5 ml) containing either polycarbophil (pH 7.6), chitosan (pH 4.5) or hydroxypropyl methylcellulose (pH 7.6) (0.5% w/v) was exposed to freshly collected buccal cells (ca. 48x10(4) cells/test) for 15 min at 30 degrees C. The cells were then rinsed with a small volume of double distilled water, allowed to air-dry on a freshy cleaved mica surface and imaged using contact mode AFM. Untreated cells showed relatively smooth surface characteristics, with many small 'crater-like' pits and indentations spread over cell surfaces. Cells that had been treated with all the investigated polymers appeared to have lost the crater and indentation characteristic and gained a higher surface roughness. These results suggest that polymer chains had adsorbed onto the cell surfaces. Quantitative image analysis of cell topography showed significant increases (P<0.05) in arithmetic roughness average (R(a)) for all the investigated polymer treated cells surfaces with respect to untreated control specimens. The changes in surface topography indicate the presence of adsorbed polymer, confirming previous work. This study demonstrates the suitability of AFM as a powerful and sensitive technique for detecting and imaging bioadhesive polymers present on mucosal cell surfaces. PMID:10867257

  8. Bioadhesive nanoareas in antifouling matrix for highly efficient affinity sensors

    NASA Astrophysics Data System (ADS)

    Mannelli, I.; Valsesia, A.; Lisboa, P.; Anger-Leroy, M.; Mornet, S.; Colpo, P.; Rossi, F.

    2008-08-01

    A procedure for fabricating nanopatterned surfaces at the sub-500 nm scale comprising a hexagonal close packed array of bioadhesive gold nanoareas in a protein resistant matrix (PEO-like polymer), has been optimized. The surfaces were characterized by AFM analysis and their interaction with amino functionalised gold nanoparticles as models were investigated. The AFM images show the crystalline arrangement of nanopattern array and the localized adsorption of the H2N-Au nanoparticles in the bioadhesive nanoareas. A Surface Plasmon Resonance imaging (SPRi) system was used to assess the detection performances of these surfaces when employed as a transduction platform for studying biomolecule interactions. The investigated surfaces showed an enhancement of the affinity reaction efficiency with respect to the non structured surfaces. The obtained preliminary results show that nanostructuring the surfaces improve the binding site accessibility of the immobilized biological probes without significantly modifying the native biomolecule conformation.

  9. What would we do without metronidazole?

    PubMed

    Stover, Kayla R; Riche, Daniel M; Gandy, Christie L; Henderson, Harold

    2012-04-01

    Metronidazole is a treatment of choice for several types of infections, but coexisting conditions or concomitant medications may preclude its use. Although tinidazole, a newer nitroimidazole, may be an option in cases where drug interactions make the use of metronidazole inadvisable, similar absolute contraindications exist. In situations where nitroimidazole use is contraindicated or inadvisable, clinicians may have difficulty deciding on efficacious treatment options. For the treatment of trichomoniasis, alternatives include furazolidone, clotrimazole, nonoxynol-9 or paromomycin. Alternatives for bacterial vaginosis include clindamycin topically or systemically. For giardiasis, alternative options include paromomycin, nitazoxanide or the antihelminthic benzimidazoles. Alternatives for Clostridium difficile are varied, including oral vancomycin, nitazoxanide and rifaximin. Although options are limited, alternative therapies for treatment of patients with absolute contraindications to the nitroimidazole antibiotics are available. PMID:21817887

  10. QbD-Oriented Development and Characterization of Effervescent Floating-Bioadhesive Tablets of Cefuroxime Axetil.

    PubMed

    Bansal, Sanjay; Beg, Sarwar; Garg, Babita; Asthana, Abhay; Asthana, Gyati S; Singh, Bhupinder

    2016-10-01

    The objective of the present studies was systematic development of floating-bioadhesive gastroretentive tablets of cefuroxime axetil employing rational blend of hydrophilic polymers for attaining controlled release drug delivery. As per the QbD-based approach, the patient-centric target product profile and quality attributes of tablet were earmarked, and preliminary studies were conducted for screening the suitability of type of polymers, polymer ratio, granulation technique, and granulation time for formulation of tablets. A face-centered cubic design (FCCD) was employed for optimization of the critical material attributes, i.e., concentration of release controlling polymers, PEO 303 and HPMC K100 LV CR, and evaluating in vitro buoyancy, drug release, and ex vivo mucoadhesion strength. The optimized formulation was embarked upon through numerical optimization, which yield excellent floatation characteristic with drug release control (i.e., T 60% > 6 h) and bioadhesion strength. Drug-excipient compatibility studies through FTIR and P-XRD revealed the absence of any interaction between the drug and polymers. In vivo evaluation of the gastroretentive characteristics through X-ray imaging and in vivo pharmacokinetic studies in rabbits revealed significant extension in the rate of drug absorption (i.e., T max, K a, and MRT) from the optimized tablet formulation as compared to the marketed formulation. Successful establishment of various levels of in vitro/in vivo correlations (IVIVC) substantiated high degree of prognostic ability of in vitro dissolution conditions in predicting the in vivo performance. In a nutshell, the studies demonstrate successful development of the once-a-day gastroretentive formulations of cefuroxime axetil with controlled drug release profile and improved compliance.

  11. Clinical trials with metronidazole in human balantidiasis.

    PubMed

    Garcia-Laverde, A; de Bonilla, L

    1975-09-01

    Therapeutic activity of metronidazole against Balantidium coli was evaluated by using two drug regimens in 20 human cases of balantidiasis. All patients also harbored Trichuris trichiura. Children received a total amount of drug that varied from 2.5 g during 5 days to 7.5 g in a period of 10 days. Adults were given 5 g in 5 days or 12.5 g during a period of 10 days. In all patients B. coli disappeared after the 4th day of treatment. Frequent posttreatment stool examination remained negative. All patients tolerated the drug well and there were no side effects. PMID:1190365

  12. Metronidazole-induced alterations in murine spermatozoa morphology.

    PubMed

    Mudry, Marta D; Palermo, Ana M; Merani, María S; Carballo, Marta A

    2007-02-01

    The aim of this work was to assess the effect of metronidazole (MTZ) on the stages of the seminiferous epithelial cycle and spermatozoa morphology when the drug is administered in human therapeutic doses to 60-day-old CFW male mice. The frequency of the stages was established by counting spermatocytes in pachytene and spermatids. Abnormalities in the flagellum or the head, lack of maturity and multiple malformations, were considered in the morphological analysis. Murine control strain was compared with MTZ treated group (v.ip 130 mg/kg/bw) both kept in standard captivity conditions. Cellular composition or number of stages in the seminiferous tubules were not altered in MTZ exposed animals, though the number of cells in stages I, V and XII was increased. The sperm cell morphology was severely affected by the treatment with potentially serious consequences on the normal fertilization process. Thus, the MTZ has to be considered as a conceivable thread regarding male fertility. PMID:17184970

  13. Formulation and evaluation of atenolol floating bioadhesive system using optimized polymer blends

    PubMed Central

    Siddam, Haritha; Kotla, Niranjan G.; Maddiboyina, Balaji; Singh, Sima; Sunnapu, Omprakash; Kumar, Anil; Sharma, Dinesh

    2016-01-01

    Introduction: Oral sustained release gastro retentive dosage forms offer several advantages for drugs having absorption from the upper gastrointestinal tract to improve the bioavailability of medications which have narrow absorption window. The aim of the study was to develop a floating bioadhesive drug delivery system exhibiting a unique combination of floatation and bioadhesion to prolong the residence in the stomach using atenolol as a model drug. Methods: Prior to compression, polymeric blend(s) were evaluated for flow properties. The tablets were prepared by direct compression method using bioadhesive polymer like Carbopol 934P and hydrophilic polymers like HPMC K4M, HPMC K15M, and HPMC K100M. The prepared tablets were evaluated for physical characteristics, bioadhesive strength, buoyancy lag time, swelling index and in vitro drug release studies. Results: The mean bioadhesive strength was found to be in the range of 16.2 to 52.1 gm. The optimized blend (F11) showed 92.3% drug releases after 24 hrs. Whilst, increase in concentration of carbopol 934P, bioadhesive strength and swelling index was increased with slow release. The n values of optimized formulations were found in the range of 0.631-0.719 indicating non-fickian anomalous type transport mechanism. Conclusion: The study aided in developing an ideal once-a-day gastro retentive floating drug delivery system with improved floating, swelling and bioadhesive characteristics with better bioavailability. PMID:27051631

  14. 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

  15. Molecular basis of metronidazole resistance in pathogenic bacteria and protozoa.

    PubMed

    Land, Kirkwood M.; Johnson, Patricia J.

    1999-10-01

    The molecular basis of metronidazole resistance has been examined in anaerobic bacteria, such as Bacteroides, Clostridium, and Helicobacter, and anaerobic parasitic protists such as Giardia, Entamoeba, and trichomonads. A variety of enzymatic and cellular alterations have been shown to correlate with metronidazole susceptibility in these pathogens; however, a common theme has been revealed. Resistant cells are typically deficient in drug activation. The frequent correlation between metronidazole resistance and ineffective drug activation suggests that drug resistance is the result of modification of proteins involved in drug activation. Copyright 1999 Harcourt Publishers Ltd.

  16. Preparation and evaluation of glyceryl monooleate-coated hollow-bioadhesive microspheres for gastroretentive drug delivery.

    PubMed

    Liu, Yuanfen; Zhang, Jianjun; Gao, Yuan; Zhu, Jiabi

    2011-07-15

    The purpose of this study was to produce hollow and bioadhesive microspheres to lengthen drug retention time in the stomach. In these microspheres, ethylcellulose was used as the matrix, Eudragit EPO was employed to modulate the release rate, and glyceryl monooleate (GMO) was the bioadhesive polymer in situ. The morphological characteristics of the microspheres were defined using scanning electron microscopy. The in vitro release test showed that the release rate of drug from the microspheres was pH-dependent, and was not influenced by the GMO coating film. The prepared microspheres demonstrated strong mucoadhesive properties with good buoyancy both in vitro and in vivo. Pharmacokinetic analysis indicated that the elimination half-life time of the hollow-bioadhesive microspheres was prolonged, and that the elimination rate was decreased. In conclusion, the hollow-bioadhesive synergic drug delivery system may be advantageous in the treatment of stomach diseases.

  17. Injectable citrate-based mussel-inspired tissue bioadhesives with high wet strength for sutureless wound closure.

    PubMed

    Mehdizadeh, Mohammadreza; Weng, Hong; Gyawali, Dipendra; Tang, Liping; Yang, Jian

    2012-11-01

    The existing surgical adhesives are not ideal for wet tissue adhesion required in many surgeries such as those for internal organs. Developing surgical adhesives with strong wet tissue adhesion, controlled degradability and mechanical properties, and excellent biocompatibility has been a significant challenge. Herein, learning from nature, we report a one-step synthesis of a family of injectable citrate-based mussel-inspired bioadhesives (iCMBAs) for surgical use. Within the formulations investigated, iCMBAs showed 2.5-8.0 folds stronger wet tissue adhesion strength over the clinically used fibrin glue, demonstrated controlled degradability and tissue-like elastomeric mechanical properties, and exhibited excellent cyto/tissue-compatibility both in vitro and in vivo. iCMBAs were able to stop bleeding instantly and suturelessly, and close wounds (2 cm long×0.5 cm deep) created on the back of Sprague-Dawley rats, which is impossible when using existing gold standard, fibrin glue, due to its weak wet tissue adhesion strength. Equally important, the new bioadhesives facilitate wound healing, and are completely degraded and absorbed without eliciting significant inflammatory response. Our results support that iCMBA technology is highly translational and could have broad impact on surgeries where surgical tissue adhesives, sealants, and hemostatic agents are used.

  18. Single-dose metronidazole clears Opalina sp. from juvenile Bufo woodhousii.

    PubMed

    Nickol, Devin R; Tufts, Danielle M

    2013-06-01

    Protozoans of the family Opalinidae are intestinal commensals in amphibians. To test the hypothesis that these organisms are susceptible to the antiprotozoal antibiotic metronidazole, we randomly assigned 60 juvenile Woodhouse's toads ( Bufo woodhousii ) to receive a single oral dose of metronidazole or water. In pilot trials, the prevalence of opalinids in untreated members of this population was over 70%. One-third of the study population was dissected at each of 3 time points: 18 hr, 1 wk, and 2 wk post-treatment. An examiner blinded to the toad's treatment history determined the presence or absence of opalinids using a dissecting microscope. Opalinids were found in 3/10 toads in the treatment group and 9/10 in the control group after 18 hr (P < 0.02), in none of the treatment group and 8/10 in the control group after 1 wk (P < 0.001), and in none of the treatment group and 10/10 in the control group after 2 wk (P < 0.0001). These results suggest that a single-dose of metronidazole quickly and reliably clears opalinids from juvenile Woodhouse's toads with no evidence of short-term recurrence. The treatment was well tolerated, with no apparent morbidity and no mortality in either group. Future exploration of opalinid-related host fitness consequences may be facilitated by this simple method of developing a protozoan-free host population. PMID:23339344

  19. 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.

  20. 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. PMID:26304821

  1. Treatment of Infections Caused by Metronidazole-Resistant Trichomonas vaginalis

    PubMed Central

    Cudmore, Sarah L.; Delgaty, Kiera L.; Hayward-McClelland, Shannon F.; Petrin, Dino P.; Garber, Gary E.

    2004-01-01

    Infections with the sexually transmitted protozoan Trichomonas vaginalis are usually treated with metronidazole, a 5-nitroimidazole drug derived from the antibiotic azomycin. Metronidazole treatment is generally efficient in eliminating T. vaginalis infection and has a low risk of serious side effects. However, studies have shown that at least 5% of clinical cases of trichomoniasis are caused by parasites resistant to the drug. The lack of approved alternative therapies for T. vaginalis treatment means that higher and sometimes toxic doses of metronidazole are the only option for patients with resistant disease. Clearly, studies of the treatment and prevention of refractory trichomoniasis are essential. This review describes the mechanisms of metronidazole resistance in T. vaginalis and provides a summary of trichomonicidal and vaccine candidate drugs. PMID:15489348

  2. 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. PMID:25161176

  3. Double-blind, randomized pilot study of bioadhesive chlorhexidine gel in the prevention and treatment of mucositis induced by chemoradiotherapy of head and neck cancer

    PubMed Central

    Diaz-Sanchez, Rosa-Maria; Pachón-Ibáñez, Jerónimo; Marín-Conde, Fátima; Rodríguez-Caballero, Ángela; Gutierrez-Perez, Jose-Luis

    2015-01-01

    Background To evaluate, in an initial way, the effectiveness of bioadhesive chlorhexidine gel 0.2% versus placebo as a preventive and therapeutic intervention of oral mucositis induced by radiation therapy and chemotherapy in patients diagnosed with head and neck cancer treated with chemoradiotherapy. Material and Methods In this pilot study, 7 patients (range of age: 18- 65), having histological documented diagnosis of squamous carcinoma on the head and neck region in stage III and IV, and receiving combined radiation treatment and chemotherapy (cisplatin 100 mg/m2 IV on days 1, 22, and 43 of irradiation) were studied. Simultaneously, a topical application was performed with bioadhesive chlorhexidine gel 0.2% in the study group, and the placebo gel for the control group in 5 applications per day, from the time of initiation of cancer treatment to 2 weeks after completion of chemo-radiotherapy treatment (11 weeks of follow-up). The gradation of mucositis, pain, analgesic consumption, infectious complications, and treatment tolerance was measured. Results After 7 patients completed the protocol, any differences were observed between groups in an interval analysis. Mucositis, pain, and tolerance was similar in both groups. Conclusions Our results must be interpreted with caution due to the reduced sample size, but the use of bioadhesive chlorhexidine gel 0.2% didn’t contribute clinical improvement to the oral mucositis induced by radiation therapy and chemotherapy. Key words: Chlorhexidine, mucositis, head and neck cancer. PMID:25662553

  4. Preparation and characterization of glycoprotein-resistant starch complex as a coating material for oral bioadhesive microparticles for colon-targeted polypeptide delivery.

    PubMed

    Situ, Wenbei; Li, Xiaoxi; Liu, Jia; Chen, Ling

    2015-04-29

    For effective oral delivery of polypeptide or protein and enhancement their oral bioavailability, a new resistant starch-glycoprotein complex bioadhesive carrier and an oral colon-targeted bioadhesive delivery microparticle system were developed. A glycoprotein, concanavalin A (Con A), was successfully conjugated to the molecules of resistant starch acetate (RSA), leading to the formation of resistant starch-glycoprotein complex. This Con A-conjugated RSA film as a coating material showed an excellent controlled-release property. In streptozotocin (STZ)-induced type II diabetic rats, the insulin-loaded microparticles coated with this Con A-conjugated RSA film exhibited good hypoglycemic response for keeping the plasma glucose level within the normal range for totally 44-52 h after oral administration with different insulin dosages. Oral glucose tolerance tests indicated that successive oral administration of these colon-targeted bioadhesive microparticles with insulin at a level of 50 IU/kg could achieve a hypoglycemic effect similar to that by injection of insulin at 35 IU/kg. Therefore, the potential of this new Con A-conjugated RSA film-coated microparticle system has been demonstrated to be capable of improving the oral bioavailability of bioactive proteins and peptides.

  5. Bioadhesion to model thermally responsive surfaces

    NASA Astrophysics Data System (ADS)

    Andrzejewski, Brett Paul

    contrast possessed no adhesion to the pure component C11EG6OH SAM at both temperatures examined, 25 and 40°C. The protein adhesion data to the mixed SAM also supports the hypothesis that the mixed SAM displays a non-fouling molecular conformation at 25°C whereas it displays a dominantly fouling molecular conformation at 40°C. Advancing contact angles obtained through tensiometry were used to find the surface free energy of the mixed SAM before and after the thermal response using the van Oss-Good-Chaudhury method. The surface tension values obtained, 42 and 38 mN/m for 22 and 40°C, respectively, are not dissimilar enough with regard to error to make conclusions. In a similar manner, the surface free energy of another mixed SAM composed of alkyl and trimethylamine thiolates was also calculated. PNIPAAm brushes grown on a silicon substrate by atom-transfer radical polymerization (ATRP) were imaged by AFM and characterized by XPS. The height of the resulting brushes could be controlled from ˜5 to 55 nm by reaction time. A thermal response was observed for polymer brushes with a length greater than 20 nm. For polymer brush lengths greater than 20 nm, the static contact angle at 22°C was 35° and varied from 60 to 80° at 40°C. The thermal response was also observed using the captive bubble method. Force-distance curves of the PNIPAAm brushes were taken with an unmodified silicon nitride AFM cantilever at incremental temperature steps. At room temperature the force-distance data was fit to the Alexander-de Gennes model resulting in a hydrated polymer length of 235 nm. The Young's modulus was calculated using the Hertz model and changed from ˜80 MPa at 26°C to ˜350 MPa at 40°C. The solvent condition of the Alexander-de Gennes model was set to the case of good solvent and showed close match to the force-distance data at 26°C. The match was not as close when the solvent condition was set to theta solvent condition and compared to the force-distance data at 40

  6. Spectrophotometric determination of metronidazole and secnidazole in pharmaceutical preparations.

    PubMed

    Saffaj, T; Charrouf, M; Abourriche, A; Abboud, Y; Bennamara, A; Berrada, M

    2004-10-01

    A rapid and sensitive spectrophotometric method is proposed for determination of metronidazole and secnidazole. The method depends on the reduction of metronidazole and secnidazole molecule with zinc dust and hydrochloric acid flowed by diazotization and coupling with 8-quinolinol to give red colored chromogens easily measured spectrophotometrically which has lambda(max) = 500 nm. The experimental conditions were optimized and Berr's law was obeyed over the applicable concentration ranges both techniques were applied successfully to a wide variety of pharmaceutical preparations. PMID:15474063

  7. 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.

  8. 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.

  9. Glyceryl monooleate-coated bioadhesive hollow microspheres of riboflavin for improved gastroretentivity: optimization and pharmacokinetics.

    PubMed

    Upadhyay, Mayank Shekhar; Pathak, Kamla

    2013-06-01

    The bioadhesive hollow microspheres of riboflavin were developed as a site-specific gastroretentive system to prolong the residence time of drug in the stomach and, consequently, to enhance the bioavailability. Hollow microspheres (M1-M9) prepared by the emulsion solvent diffusion method using ethyl cellulose and Eudragit E100 as shell-forming polymers were designed using 3(2) full factorial design. The optimized formulation (M5) with 93.23 ± 0.6 % entrapment efficiency and 75.39 ± 3.4 % cumulative drug release at 8 h was subjected to coating with a bioadhesive layer of glyceryl monooleate (GMO) to obtain BM5. It exhibited excellent in vitro buoyancy for 12 h (100 %), in vitro bioadhesion (88.33 ± 2.35 %), and presented micromeritic properties amenable to processing steps. Scanning electron microscopy depicted a spherical shape and hollow cavity of microspheres and evidenced smooth surface coating of GMO. The compatibility of drug and excipients and the absence of interaction were determined using differential scanning calorimetry and diffuse reflectance spectroscopy, respectively. The in vitro release from BM5 (novel release apparatus) demonstrated that drug release was not hindered by the bioadhesive coating layer of GMO. The pharmacokinetic study provided convincing evidence for the increased absorption of riboflavin and bioavailability (Fr = 178.47 %) from bioadhesive hollow microspheres. Conclusively, the study demonstrated the superiority of the synergistic approach of floating and bioadhesive system over either floating or bioadhesive system for the prolongation of gastric residence time of riboflavin to improve its absorption.

  10. Metronidazole Decreases Viability of DLD-1 Colorectal Cancer Cell Line

    PubMed Central

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

    2013-01-01

    Abstract 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. PMID:23777253

  11. Metronidazole pharmacokinetics in patients with acute renal failure.

    PubMed

    Somogyi, A A; Kong, C B; Gurr, F W; Sabto, J; Spicer, W J; McLean, A J

    1984-02-01

    The pharmacokinetics and metabolism of intravenous metronidazole were studied in six patients with acute renal failure. In two of the patients a single dose (500 mg) of metronidazole was administered, whereas in four patients the steady-state pharmacokinetics were studied after four days therapy of 500 mg twice daily. Plasma concentrations of metronidazole and its hydroxy and acetic acid metabolites were measured by a specific and sensitive HPLC method. The volume of distribution was 0.65 +/- 0.13 l/kg (mean +/- S.D.), elimination half-life was 9.9 +/- 2.5 h and total plasma clearance was 55.5 +/- 17.7 ml/min. Renal clearance was almost non-existent (1.4 +/- 1.4 ml/min), whereas non-renal clearance was 54.0 +/- 18.2 ml/min. Steady-state plasma concentrations of metronidazole were 15.3 +/- 3.8 mg/l, the hydroxy metabolite were 17.4 +/- 2.0 mg/l and the acetic acid metabolite were 1.2 +/- 0.8 mg/l. In the patients studied, a dosing regimen of 500 mg twice daily resulted in therapeutically adequate blood levels of metronidazole. PMID:6706889

  12. Investigations on interpolymer complexes of cationic guar gum and xanthan gum for formulation of bioadhesive films.

    PubMed

    Singh, M; Tiwary, A K; Kaur, G

    2010-07-01

    The present study was aimed at evaluating the possible use of inter polymer complexed (IPC) films of xanthan gum (XG) and cationic guar gum (CGG) for formulating domperidone bioadhesive films. Formation of bonds between -COO¯ groups of XG and -N(+)(CH(3))(3) groups of CGG was evident in the FTIR spectra of IPC films. Bioadhesive strength of the films was evaluated employing texture analyser. Water uptake studies indicated swelling to be a function of XG concentration in the interpolymer complexes. The bioadhesive films were found to possess neutral pH. In vitro drug release studies and residence time studies indicated that the film comprising CGG:XG (80:20) released 98% of domperidone in 8 h and exhibited a residence time of approximately 8 h. Enhanced bioavailability of domperidone was observed from bioadhesive films as compared to orally administered conventional tablets. Overall, the findings suggest that IPC films of XG and CGG, exhibiting desired bioadhesive strength and enhanced bioavailability of domperidone, can be prepared. PMID:21589796

  13. Can bioadhesive nanoparticles allow for more effective particle uptake from the small intestine?

    PubMed

    Reineke, J; Cho, D Y; Dingle, Y L; Cheifetz, P; Laulicht, B; Lavin, D; Furtado, S; Mathiowitz, E

    2013-09-28

    There has been increasing interest in developing bioadhesive nanoparticles due to their great potential as carriers for therapeutics in oral drug delivery systems. Despite decades of research, such a system still has not been successfully implemented. This paper demonstrates the enormous potential of such engineered systems: the incorporation of a bioadhesive coating, poly(butadiene-maleic anhydride-co-L-DOPA) (PBMAD), to non-bioadhesive nanospheres resulted in an enhancement of particle uptake in the small intestine from 5.8±1.9% to 66.9±12.9%. Direct correlation was obtained between bulk tensile strength, in vitro binding to everted intestinal sacs and quantitative in vivo uptake; this data suggests that bulk properties of polymers can be used to predict bioadhesive properties of nano- and microparticles. The differential distribution of the nanospheres to various tissues following uptake suggests surface chemistry plays a significant role in their localization within the body. The results of these studies provide strong support for the use of bioadhesive polymers to enhance nano- and micro-particle uptake from the small intestine for oral drug delivery. PMID:23796432

  14. In vitro anti-trichomonad effectiveness of a gossypol-metronidazol blend.

    PubMed

    Teresa González-Garza, M; Said-Fernández, S

    1997-06-01

    With the aid of the Basic Sequential Analytical Simplex Method the in vitro anti-trichomonad effectiveness of several metronidazole/gossypol blends was determined. While the combination that produced 50% of growth inhibition on trichomonad cultures (IC50) contained 15.1 microM gossypol and 0.087 microM metronidazole, the IC(50) of metronidazole and gossypol tested separately was 38.08 microM and 0.195 microM, respectively. Thus, the IC50 of mixed gossypol and metronidazole was, respectively 60.34 and 55.4% lower than that of each separated drug. Whereas metronidazole is usually administered orally, gossypol, used as spermicide, is formulated as pessary. In such conditions the absorption of metronidazole is very efficient while that of gossypol is strikingly poor. The above suggest that a gossypol-metronidazole anti-trichomoniasis therapeutic scheme could be as effective as metronidazole alone, but less toxic. PMID:18611820

  15. Fragmentation of Injectable Bioadhesive Hydrogels Affords Chemotherapeutic Macromolecules.

    PubMed

    Yamada, Yuji; Schneider, Joel P

    2016-08-01

    Implantation of drug delivery depots into or proximal to targeted tissue is an effective method to deliver anticancer drugs in a sustained localized manner. Herein, syringe-injectable polydextran aldehyde (PDA)-based bioadhesive gels are prepared that can locally deliver cytotoxins upon their hydrolytic fragmentation. Adhesive gels are formed by mixing doxorubicin (DOX)-functionalized PDA (DOX-PDA) and bovine serum albumin (BSA) using a dual-barrel syringe. Upon mixing and delivery, the DOX-PDA reacts with the cross-linker BSA as well as the extracellular matrix via imine bond formation to define the cohesive and adhesive properties of the gel, respectively. Resulting gels are mechanically rigid (∼10 kPa) and adherent (adhesive stress ∼ 4 kPa). Once formed, the DOX-PDA-BSA gels undergo slow hydrolytic degradation (>2 months) locally releasing free DOX and DOX-PDA as expected. Surprisingly, we found that macromolecules composed of DOX, PDA, and BSA are also released from the bulk material. These DOX-PDA-BSA macromolecules, along with free DOX and DOX-PDA conjugate, are internalized by A549 lung carcinoma cells, resulting in potent cell death.

  16. Bioadhesion in ascidians: a developmental and functional genomics perspective

    PubMed Central

    Pennati, Roberta; Rothbächer, Ute

    2015-01-01

    The development of bioadhesives inspired from marine animals is a promising approach to generate new tissue-compatible medical components. A number of marine species, through their adhesive properties, also represent significant foulers that become increasingly problematic to aquaculture, shipping or local biodiversity. In order to develop more sophisticated man-made glues and/or efficient fouling resistant surfaces, it is important to understand the mechanical, structural and molecular properties of adhesive organs in selected species. Ascidians are marine invertebrates with larvae that opportunistically attach to almost any type of submerged surface to undergo metamorphosis into permanently sessile adults. Not only do they represent a globally important fouling organism, but they are becoming increasingly popular as model organisms for developmental biology. The latter is due to their phylogenetic position as the sister group to the vertebrates and their cellular and molecular accessibility for experimentation. In this paper, we review the mechanisms of larval adhesion in ascidians and draw conclusions from comparative analyses of selected species. We further discuss how knowledge from a developmental and functional genomics point of view can advance our understanding of cellular and molecular signatures and their hierarchical usage in animal adhesive organs. PMID:25657840

  17. Metronidazole-Induced Bullous Pemphigoid: A Case Report.

    PubMed

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

    2015-12-01

    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

  18. Bioinspired polyethylene terephthalate nanocone arrays with underwater superoleophobicity and anti-bioadhesion properties.

    PubMed

    Liu, Wendong; Liu, Xueyao; Fangteng, Jiaozi; Wang, Shuli; Fang, Liping; Shen, Huaizhong; Xiang, Siyuan; Sun, Hongchen; Yang, Bai

    2014-11-21

    This paper presents a facile method to fabricate bioinspired polyethylene terephthalate (PET) nanocone arrays via colloidal lithography. The aspect ratio (AR) of the nanocones can be finely modulated ranging from 1 to 6 by regulating the etching time. The samples with the AR value of 6 can present underwater superoleophobicity with the underwater oil contact angle (OCA) of 171.8°. The as-prepared PET nanocone arrays perform anti-bioadhesion behavior, which inhibits the formation of the actin cytoskeleton when it used as the substrate for cell culture. Moreover, the oil wettability is temperature controlled after modifying the PET nanocone arrays with PNIPAAm film, and the oil wettability of the functionalized nanocone arrays can be transformed from the superoleophobic state with OCA about 151° to the oleophilic state with OCA about 25° reversibly. Due to the high-throughput, parallel fabrication and cost-efficiency of this method, it will be favourable for researchers to introduce oleophobic properties to various substrate and device surfaces. Due to the superoleophobicity and simple functionalizing properties, the PET nanocone arrays are very promising surfaces for anti-adhesion, self-cleaning and have potential applications in material, medical, and biological fields. PMID:25303770

  19. Bioinspired polyethylene terephthalate nanocone arrays with underwater superoleophobicity and anti-bioadhesion properties.

    PubMed

    Liu, Wendong; Liu, Xueyao; Fangteng, Jiaozi; Wang, Shuli; Fang, Liping; Shen, Huaizhong; Xiang, Siyuan; Sun, Hongchen; Yang, Bai

    2014-11-21

    This paper presents a facile method to fabricate bioinspired polyethylene terephthalate (PET) nanocone arrays via colloidal lithography. The aspect ratio (AR) of the nanocones can be finely modulated ranging from 1 to 6 by regulating the etching time. The samples with the AR value of 6 can present underwater superoleophobicity with the underwater oil contact angle (OCA) of 171.8°. The as-prepared PET nanocone arrays perform anti-bioadhesion behavior, which inhibits the formation of the actin cytoskeleton when it used as the substrate for cell culture. Moreover, the oil wettability is temperature controlled after modifying the PET nanocone arrays with PNIPAAm film, and the oil wettability of the functionalized nanocone arrays can be transformed from the superoleophobic state with OCA about 151° to the oleophilic state with OCA about 25° reversibly. Due to the high-throughput, parallel fabrication and cost-efficiency of this method, it will be favourable for researchers to introduce oleophobic properties to various substrate and device surfaces. Due to the superoleophobicity and simple functionalizing properties, the PET nanocone arrays are very promising surfaces for anti-adhesion, self-cleaning and have potential applications in material, medical, and biological fields.

  20. 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.

  1. Fast-drying multi-laminate bioadhesive films for transdermal and topical drug delivery.

    PubMed

    Donnelly, Ryan F; McCarron, Paul A; Morrow, Desmond I J; Woolfson, A David

    2013-11-01

    No bioadhesive patch-based system is currently marketed. This is despite an extensive number of literature reports on such systems detailing their advantages over conventional pressure sensitive adhesive-based patches in wet environments and describing successful delivery of a diverse array of drug substances. This lack of proprietary bioadhesive patches is largely due to the fact that such systems are exclusively water-based, meaning drying is difficult. In this paper we describe, for the first time, a novel multiple lamination method for production of bioadhesive patches. In contrast to patches produced using a conventional casting approach, which took 48 hours to dry, bioadhesive films prepared using the novel multiple lamination method were dried in 15 min and were folded into formed patches in a further 10 min. Patches prepared by both methods had comparable physicochemical properties. The multiple lamination method allowed supersaturation of 5-aminolevulinic acid to be achieved in formed patch matrices. However, drug release studies were unable to show an advantage for supersaturation with this particular drug, due to its water high solubility. The multiple lamination method allowed greater than 90% of incorporated nicotine to remain within formed patches, in contrast to the 48% achieved for patches prepared using a conventional casting approach. The procedure described here could readily be adapted for automation by industry. Due to the reduced time, energy and ensuing finance now required, this could lead to bioadhesive patch-based drug delivery systems becoming commercially viable. This would, in turn, mean that pathological conditions occurring in wet or moist areas of the body could now be routinely treated by prolonged site-specific drug delivery, as mediated by a commercially produced bioadhesive patch.

  2. Evidence for bioadhesive effects of polysaccharides and polysaccharide-containing herbs in an ex vivo bioadhesion assay on buccal membranes.

    PubMed

    Schmidgall, J; Schnetz, E; Hensel, A

    2000-02-01

    Aqueous extracts of polysaccharide-containing plants are widely used in therapy for irritated mucus membranes in the pharynx region. In order to prove the existence of mucilaginous effects of polysaccharide hydrocolloids on epithelia an ex vivo system based on porcine buccal membranes was established. The tissue culture was stable and there was no indication of cytolytic processes during the 5 hour incubation period. This was confirmed through histological studies and the respective LDH values as toxicity marker. The test system was shown to discriminate the adhesive effects of different raw polysaccharides, obtained from a variety of medicinal plants. While polysaccharides from Altheae officinalis, Plantago lanceolata, Malva moschata, or Tilia cordata showed only moderate bioadhesion to epithelial tissue, strong adhesive processes were observed with polysaccharides from Fucus vesiculosus and Calendula officinalis. The adhesive effects were concentration-dependent. Histological studies of membranes, incubated with a fluorescence-labelled rhamnogalacturonan, indicated the presence of distinct polysaccharide layers on the apical membrane surface. With these results, adsorption effects of certain polysaccharides on mucus membranes were shown for the first time. Such effects suggest that this may account, at least in part, for the therapeutic effects of mucilage-containing plants in the treatment of irritated buccal membranes. PMID:10705734

  3. Depletion of metronidazole in brook trout (Salvelinus fontinalis).

    PubMed

    Watson, Lynn; MacNeil, James D; Potter, Ross; Hellou, Jocelyne

    2015-01-01

    Metronidazole (MNZ), which is effective in the treatment of intestinal infections in fish, is also a suspected carcinogen and has been banned in numerous jurisdictions for use in any food-producing animal, including fish. Few reports have been published on the depletion of MNZ in fish. A depletion study was therefore undertaken using MNZ in feed provided to trout under controlled conditions. The water was maintained at 17.5 ± 0.9°C throughout the medication and depletion periods in the study. Following a 20-day acclimatisation period in the holding tanks, the trout (approximately 150-200 g bodyweight at the start of the study) were subjected to two separate medication and withdrawal periods: (A) 5 day medication/5 day withdrawal and (B) 5 day medication/16 day withdrawal. This simulated a potential multiple dosing in an aquaculture setting. In both medication periods, the trout were dosed with medicated feed containing 3 g MNZ kg(-1) fish. Fish were sacrificed in accordance with accepted animal care protocols and tissue samples were analysed by UPLC-MS/MS. Analyte concentrations in trout muscle ranged from a high of 27,000 ± 10,000 ng g(-1) for MNZ and 830 ± 570 ng g(-1) for MNZ-OH on day 1 of withdrawal period A to a low of 1.8 ± 2.3 ng g(-1) for MNZ and < 0.4 ng g(-1) for MNZ-OH on day 16 of withdrawal period B. The results demonstrate that when using the UPLC-MS/MS method, residues of MNZ may be detected in fish treated with MNZ after 16 days of withdrawal. PMID:25747325

  4. A novel ketoconazole bioadhesive effervescent tablet for vaginal delivery: design, in vitro and 'in vivo' evaluation.

    PubMed

    Wang, Lei; Tang, Xing

    2008-02-28

    Bioadhesive tablet formulations of ketoconazole for vaginal delivery were studied. Carbomer (Carbopol 974P, Carbopol 934P), hydroxypropylmethyl cellulose (HPMC) and hydroxypropyl cellulose (HPC) were used as candidate bioadhesive polymers. Effervescent was incorporated into the formulations as a disintegration agent. The swelling behavior and bioadhesive strength of the drug-free tablets were investigated. Carbopol 934P was selected as biopolymer in combination with HPMC or HPC at different ratios to develop five drug-loaded formulations. The swellings, tackiness and in vitro release were studied on the tablets. A good sustained effect and a moderate bioadhesion were obtained with the tablets. The formulation containing 100mg of effervescent, with the Carbopol 934P:HPC ratio of 1:9, seemed to be the optimum one for the tablet. In vivo drug residence tests were carried out by administering the preferred formulation to female rats. The results showed that the drug remaining followed a one-order model. Even after 24h of administration in vagina of rats, 17% of the original employed drug was retained on the vaginal tissue. Our study may provide a potential vaginal tablet formulation of ketoconazole against Candida albicans. PMID:17920795

  5. A novel ketoconazole bioadhesive effervescent tablet for vaginal delivery: design, in vitro and 'in vivo' evaluation.

    PubMed

    Wang, Lei; Tang, Xing

    2008-02-28

    Bioadhesive tablet formulations of ketoconazole for vaginal delivery were studied. Carbomer (Carbopol 974P, Carbopol 934P), hydroxypropylmethyl cellulose (HPMC) and hydroxypropyl cellulose (HPC) were used as candidate bioadhesive polymers. Effervescent was incorporated into the formulations as a disintegration agent. The swelling behavior and bioadhesive strength of the drug-free tablets were investigated. Carbopol 934P was selected as biopolymer in combination with HPMC or HPC at different ratios to develop five drug-loaded formulations. The swellings, tackiness and in vitro release were studied on the tablets. A good sustained effect and a moderate bioadhesion were obtained with the tablets. The formulation containing 100mg of effervescent, with the Carbopol 934P:HPC ratio of 1:9, seemed to be the optimum one for the tablet. In vivo drug residence tests were carried out by administering the preferred formulation to female rats. The results showed that the drug remaining followed a one-order model. Even after 24h of administration in vagina of rats, 17% of the original employed drug was retained on the vaginal tissue. Our study may provide a potential vaginal tablet formulation of ketoconazole against Candida albicans.

  6. Benzydamine hydrochloride buccal bioadhesive gels designed for oral ulcers: preparation, rheological, textural, mucoadhesive and release properties.

    PubMed

    Karavana, Sinem Yaprak; Güneri, Pelin; Ertan, Gökhan

    2009-01-01

    This study developed and examined the characterization of Benzidamine hydrochloride (BNZ) bioadhesive gels as platforms for oral ulcer treatments. Bioadhesive gels were prepared with four different hydroxypropylmethylcellulose (HPMC) types (E5, E15, E50 and K100M) with different ratios. Each formulation was characterized in terms of drug release, rheological, mechanical properties and adhesion to a buccal bovine mucosa. Drug release was significantly decreased as the concentration and individual viscosity of each polymeric component increased due to improved viscosity of the gel formulations. The amount of drug released for the formulations ranged from 0.76 +/- 0.07 and 1.14 +/- 0.01 (mg/cm2 +/- SD). Formulations exhibited pseudoplastic flow and all formulations, increasing the concentration of HPMC content significantly raised storage modulus (G'), loss modulus (G''), dynamic viscosity (eta') at 37 degrees C. Increasing concentration of each polymeric component also significantly improved the hardness, compressibility, adhesiveness, cohesiveness and mucoadhesion but decreased the elasticity of the gel formulations. All formulations showed non-Fickian diffusion due to the relaxation and swelling of the polymers with water. In conclusion, the formulations studied showed a wide range of mechanical and drug diffusion characteristics. On the basis of the obtained data, the bioadhesive gel formulation which was prepared with 2.5% HPMC K 100M was determined as the most appropriate formulation for buccal application in means of possessing suitable mechanical properties, exhibiting high cohesion and bioadhesion. PMID:19883251

  7. Spray-dried Amioca starch/Carbopol 974P mixtures as buccal bioadhesive carriers.

    PubMed

    Ameye, D; Mus, D; Foreman, P; Remon, J P

    2005-09-14

    In the present study, spray-dried Amioca starch/Carbopol 974P mixtures were evaluated as potential buccal bioadhesive tablets. Carbopol (C 974P) concentrations from 5 to 75% were tested. All spray-dried mixtures showed a comparable or better bioadhesive capacity compared to a reference formulation (DDWM/C 974P 95/5). The bioadhesive capacities of Amioca/Carbopol 974P mixtures were improved by spray-drying. All spray-dried mixtures showed significantly higher work of adhesion values compared to their equivalent physical mixtures. The influence of Carbopol concentration on the in vivo adhesion time of placebo tablets and in vitro miconazole nitrate release was tested. The ratio Amioca/C 974P 70/30 showed the longest in vivo adhesion time (24.5+/-8.5 h). Lower and higher C 974P concentrations had a shorter in vivo adhesion time. The mixtures containing between 15 and 30% C 974P could all sustain the in vitro miconazole nitrate release over 20 h. Again, lower and higher C 974P concentrations showed a faster in vitro miconazole release. The drug loading capacity of a spray-dried mixture containing 20% C 974P was investigated in vivo in dogs using testosterone as model drug. The spray-dried mixture could be loaded with 60% drug without loosing its in vivo bioadhesive and pharmacokinetic properties. PMID:16019172

  8. Chitosan and sodium alginate-based bioadhesive vaginal tablets.

    PubMed

    El-Kamel, Amal; Sokar, Magda; Naggar, Viviane; Al Gamal, Safaa

    2002-01-01

    Metronidazole was formulated in mucoadhesive vaginal tablets by directly compressing the natural cationic polymer chitosan, loosely cross-linked with glutaraldehyde, together with sodium alginate with or without microcrystalline cellulose (MCC). Sodium carboxymethylcellulose (CMC) was added to some of the formulations. The drug content in tablets was 20%. Drug dissolution rate studies from tablets were carried out in buffer pH 4.8 and distilled water. Swelling indices and adhesion forces were also measured for all formulations. The formula (FIII) containing 6% chitosan, 24% sodium alginate, 30% sodium CMC, and 20% MCC showed adequate release properties in both media and gave lower values of swelling index compared with the other examined formulations. FIII also proved to have good adhesion properties with minimum applied weights. Moreover, its release properties (% dissolution efficiency, DE) in buffer pH 4.8, as well as release mechanism (n values), were negligibly affected by aging. Thus, this formula may be considered a good candidate for vaginal mucoadhesive dosage forms.

  9. New approach for local delivery of rapamycin by bioadhesive PLGA-carbopol nanoparticles.

    PubMed

    Zou, Weiwei; Cao, Guangqing; Xi, Yanwei; Zhang, Na

    2009-01-01

    Local delivery of antiproliferative drugs encapsulated in biodegradable nanoparticles has shown promise as an experimental strategy for preventing vascular restenosis development. The general aim of this work was to develop polymeric nanoparticle carriers with bioadhesive properties, and to evaluate its adjuvant potential for local, intramural delivery of rapamycin for inhibition of restenosis. The bioadhesive rapamycin-loaded PLGA nanoparticles were obtained by applying carbopol 940 of different concentrations as stabilizer and bioadhesive agent. The resultant nanoparticles were characterized concerning physicochemical properties such as morphology, particle size, zeta potential, entrapment efficiency, drug loading, drug release in vitro, stability in vitro as well as the arterial uptake and retention ability in an ex-vivo model. The results revealed that carbopol could serve as a better stabilizer in the preparation of rapamycin-loaded PLGA nanoparticles compared with PVA, and the physicochemical characteristics of the obtained PLGA nanoparticles were affected by the concentration of carbopol. Furthermore, it was found that carbopol could impart the nanoparticles with bioadhesive properties, improving the rentention and uptake of nanoparticles in the arterial wall, benefiting the nanoparticles for efficient localization of therapeutic agents in restenosis site. Cell viability assay results showed that blank PLGA-carbopol nanoparticles exhibited low toxicity and excellent biocompatibility and rapamycin-loaded nanoparticles with a smaller particle size (< 200 nm) had an increased antiproliferative effect on cells in comparison to free drug. These results indicated that this research might provide a potential experimental basis for the further study of carbopol stabilized bioadhesive nanoparticles against restenosis in vivo. PMID:19555304

  10. Bioinspired polyethylene terephthalate nanocone arrays with underwater superoleophobicity and anti-bioadhesion properties

    NASA Astrophysics Data System (ADS)

    Liu, Wendong; Liu, Xueyao; Fangteng, Jiaozi; Wang, Shuli; Fang, Liping; Shen, Huaizhong; Xiang, Siyuan; Sun, Hongchen; Yang, Bai

    2014-10-01

    This paper presents a facile method to fabricate bioinspired polyethylene terephthalate (PET) nanocone arrays via colloidal lithography. The aspect ratio (AR) of the nanocones can be finely modulated ranging from 1 to 6 by regulating the etching time. The samples with the AR value of 6 can present underwater superoleophobicity with the underwater oil contact angle (OCA) of 171.8°. The as-prepared PET nanocone arrays perform anti-bioadhesion behavior, which inhibits the formation of the actin cytoskeleton when it used as the substrate for cell culture. Moreover, the oil wettability is temperature controlled after modifying the PET nanocone arrays with PNIPAAm film, and the oil wettability of the functionalized nanocone arrays can be transformed from the superoleophobic state with OCA about 151° to the oleophilic state with OCA about 25° reversibly. Due to the high-throughput, parallel fabrication and cost-efficiency of this method, it will be favourable for researchers to introduce oleophobic properties to various substrate and device surfaces. Due to the superoleophobicity and simple functionalizing properties, the PET nanocone arrays are very promising surfaces for anti-adhesion, self-cleaning and have potential applications in material, medical, and biological fields.This paper presents a facile method to fabricate bioinspired polyethylene terephthalate (PET) nanocone arrays via colloidal lithography. The aspect ratio (AR) of the nanocones can be finely modulated ranging from 1 to 6 by regulating the etching time. The samples with the AR value of 6 can present underwater superoleophobicity with the underwater oil contact angle (OCA) of 171.8°. The as-prepared PET nanocone arrays perform anti-bioadhesion behavior, which inhibits the formation of the actin cytoskeleton when it used as the substrate for cell culture. Moreover, the oil wettability is temperature controlled after modifying the PET nanocone arrays with PNIPAAm film, and the oil wettability of the

  11. Development and In Vivo Evaluation of a Novel Histatin-5 Bioadhesive Hydrogel Formulation against Oral Candidiasis

    PubMed Central

    Kong, Eric F.; Tsui, Christina; Boyce, Heather; Ibrahim, Ahmed; Hoag, Stephen W.; Karlsson, Amy J.; Meiller, Timothy F.

    2015-01-01

    Oral candidiasis (OC), caused by the fungal pathogen Candida albicans, is the most common opportunistic infection in HIV+ individuals and other immunocompromised populations. The dramatic increase in resistance to common antifungals has emphasized the importance of identifying unconventional therapeutic options. Antimicrobial peptides have emerged as promising candidates for therapeutic intervention due to their broad antimicrobial properties and lack of toxicity. Histatin-5 (Hst-5) specifically has exhibited potent anticandidal activity indicating its potential as an antifungal agent. To that end, the goal of this study was to design a biocompatible hydrogel delivery system for Hst-5 application. The bioadhesive hydroxypropyl methylcellulose (HPMC) hydrogel formulation was developed for topical oral application against OC. The new formulation was evaluated in vitro for gel viscosity, Hst-5 release rate from the gel, and killing potency and, more importantly, was tested in vivo in our mouse model of OC. The findings demonstrated a controlled sustained release of Hst-5 from the polymer and rapid killing ability. Based on viable C. albicans counts recovered from tongues of treated and untreated mice, three daily applications of the formulation beginning 1 day postinfection with C. albicans were effective in protection against development of OC. Interestingly, in some cases, Hst-5 was able to clear existing lesions as well as associated tissue inflammation. These findings were confirmed by histopathology analysis of tongue tissue. Coupled with the lack of toxicity as well as anti-inflammatory and wound-healing properties of Hst-5, the findings from this study support the progression and commercial feasibility of using this compound as a novel therapeutic agent. PMID:26596951

  12. Development and In Vivo Evaluation of a Novel Histatin-5 Bioadhesive Hydrogel Formulation against Oral Candidiasis.

    PubMed

    Kong, Eric F; Tsui, Christina; Boyce, Heather; Ibrahim, Ahmed; Hoag, Stephen W; Karlsson, Amy J; Meiller, Timothy F; Jabra-Rizk, Mary Ann

    2016-02-01

    Oral candidiasis (OC), caused by the fungal pathogen Candida albicans, is the most common opportunistic infection in HIV(+) individuals and other immunocompromised populations. The dramatic increase in resistance to common antifungals has emphasized the importance of identifying unconventional therapeutic options. Antimicrobial peptides have emerged as promising candidates for therapeutic intervention due to their broad antimicrobial properties and lack of toxicity. Histatin-5 (Hst-5) specifically has exhibited potent anticandidal activity indicating its potential as an antifungal agent. To that end, the goal of this study was to design a biocompatible hydrogel delivery system for Hst-5 application. The bioadhesive hydroxypropyl methylcellulose (HPMC) hydrogel formulation was developed for topical oral application against OC. The new formulation was evaluated in vitro for gel viscosity, Hst-5 release rate from the gel, and killing potency and, more importantly, was tested in vivo in our mouse model of OC. The findings demonstrated a controlled sustained release of Hst-5 from the polymer and rapid killing ability. Based on viable C. albicans counts recovered from tongues of treated and untreated mice, three daily applications of the formulation beginning 1 day postinfection with C. albicans were effective in protection against development of OC. Interestingly, in some cases, Hst-5 was able to clear existing lesions as well as associated tissue inflammation. These findings were confirmed by histopathology analysis of tongue tissue. Coupled with the lack of toxicity as well as anti-inflammatory and wound-healing properties of Hst-5, the findings from this study support the progression and commercial feasibility of using this compound as a novel therapeutic agent. PMID:26596951

  13. Quantification of percutaneous absorption of metronidazole and levamisole in the fire-bellied toad (Bombina orientalis).

    PubMed

    Mombarg, M; Claessen, H; Lambrechts, L; Zwart, P

    1992-12-01

    Spot-on application has proved to be an effective way to reach therapeutic doses of metronidazole and levamisole in fire-bellied toads. The percutaneous absorption of metronidazole and levamisole was quantified, using an aqueous solution of 1.008 mg/ml of metronidazole and an aqueous solution of 3.767 mg/ml of levamisole. High Performance Liquid Chromatography (HPLC) analysis of the percutaneous absorption revealed that of the amount applied, 75% of metronidazole and 90% of levamisole was absorbed. This resulted during 3 days of application in dosages of 23 mg/kg BW of metronidazole and 94 mg/kg BW of levamisole. Of the absorbed substances, 48% of metronidazole and 9% of levamisole were excreted in urine and faeces as unmetabolised substances.

  14. Mechanisms of in vitro development of resistance to metronidazole in Trichomonas vaginalis.

    PubMed

    Rasoloson, Dominique; Vanácová, Stepánka; Tomková, Eva; Rázga, Jakub; Hrdy, Ivan; Tachezý, Jan; Kulda, Jaroslav

    2002-08-01

    Development of resistance against metronidazole and mechanisms responsible for this process were studied in a sexually transmitted pathogen of humans, Trichomonas vaginalis. Monitoring of changes in metabolism and protein expression that accompanied increasing resistance of strains derived from a common drug-susceptible parent (TV 10-02) showed the multistep character of the process. The aerobic type of resistance known to occur in isolates from patients non-responsive to treatment appeared at the earliest stage, followed by development of the anaerobic type of resistance which was accompanied by gradual loss of hydrogenosomal proteins associated with drug-activating pathways [pyruvate:ferredoxin oxidoreductase (PFOR), hydrogenase, ferredoxin]. Unexpectedly, the loss of PFOR did not result in acquisition of full anaerobic resistance, thus indicating an alternative source of electrons required for the drug activation. These data suggest involvement of the oxidative decarboxylation of malate in hydrogenosomes, catalysed by NAD(+)-dependent malic enzyme and subsequent transfer of reduced equivalents to the drug via NADH:ferredoxin oxidoreductase and ferredoxin. Accordingly, all components of this pathway were eliminated before the resistance was fully developed. Resistant Trichomonas vaginalis compensated the impaired function of hydrogenosomes by enhanced conversion of pyruvate to lactate in the cytosol. Further analysis of the two key enzymes involved in metronidazole activation by Northern blotting and assay for nascent mRNA showed that the insufficient expression of the PFOR protein results from decreased gene transcription, while down-regulation of malic enzyme is controlled at the mRNA level. PMID:12177340

  15. Electrospraying technique for the fabrication of metronidazole contained PLGA particles and their release profile.

    PubMed

    Prabhakaran, Molamma P; Zamani, Maedeh; Felice, Betiana; Ramakrishna, Seeram

    2015-11-01

    Advanced engineering of materials for the development of drug delivery devices provides scope for novel and versatile strategies for treatment of various diseases. 'Electrospraying' was used to prepare PLGA microparticles and further encapsulate the drug, metronidazole (Met) within the particles to function as a drug delivery system. Two different solvents were utilized for the preparation of drug loaded PLGA particles, whereby the polymeric solution in dichloromethane (DCM) produced particles of bigger sizes than using trifluoroethanol (TFE). Scanning electron microscopy showed the spherical morphology of the particles, with sizes of 3946±407nm and 1774±167nm, respectively for PLGA-Met(DCM) and PLGA-Met(TFE). The FTIR spectroscopy proved the incorporation of metronidazole in the polymer, but without any specific drug-polymer interaction. The release of the drug from the particles was studied in phosphate buffered saline, where a sustained drug release was obtained for at least 41days. Cytotoxicity evaluation of the drug extract using mesenchymal stem cells (MSCs) showed not hindering the proliferation of MSCs, and the cell phenotype was retained after incubation in the drug containing media. Electrospraying is suggested as a cost-effective and single step process for the preparation of polymeric microparticles for prolonged and controlled release of drug. PMID:26249566

  16. Once Daily Dosing of Ceftriaxone and Metronidazole in Children With Perforated Appendicitis

    PubMed Central

    Ally, Saudia; Kelly, Brian; Kays, David; Thames, Lisa

    2016-01-01

    OBJECTIVES: The aim of this study was to compare hospital length of stay and rate of infectious complications in children with perforated appendicitis based on the postoperative antibiotic administered. METHODS: This study was a retrospective analysis of children with perforated appendicitis who underwent an appendectomy at a large academic medical center from 2008 to 2013. The primary outcome was hospital length of stay. The secondary outcomes were rates of abscess formation, wound infection, and 30-day readmissions. RESULTS: One hundred and twenty-three patients were included. Sixty-six patients (53%) were administered ceftriaxone and metronidazole once daily; 57 (47%) were administered other antibiotic regimens, which consisted of single, double, or triple antibiotic therapy with a beta-lactam backbone. There was no difference between the groups in terms of postoperative length of stay (5.7 versus 5.8 days, p = 0.83), postoperative abscess rate (8% versus 4%, p = 0.57), postoperative wound infection rate (5% versus 2%, p = 0.73), and 30-day readmissions (3% versus 11%, p = 0.19). CONCLUSIONS: While there was no statistically significant difierence in the outcomes evaluated, the rate of infectious complications was twofold higher in those given ceftriaxone and metronidazole than in others. A larger prospective randomized controlled trial is warranted to better understand the risks of using these agents. PMID:27199621

  17. 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

  18. 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.

  19. Formulation development and stability studies of aqueous metronidazole benzoate suspensions containing various suspending agents.

    PubMed

    Zietsman, Sharon; Kilian, Gareth; Worthington, Matthew; Stubbs, Chris

    2007-02-01

    Metronidazole is a synthetic antibacterial and antiprotozoan agent. Crystallization occurs in aqueous metronidazole benzoate suspensions caused by an anhydrate to monohydrate conversion. This study aimed to develop an aqueous metronidazole benzoate suspension that does not exhibit this hydration and the accompanying crystal growth. Four suspending agent systems were evaluated. Xanthan gum and Avicel RC-591 (a combination of microcrystalline cellulose and carboxymethylcellulose sodium) were found to be the suspending agents that resulted in optimal formulation properties. Monohydrate formation did not occur in product containing Avicel RC-591, indicating that suspending agents may exert a positive effect on metronidazole benzoate suspension stability. PMID:17454051

  20. 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.

  1. Medicated tampons: intravaginal sustained administration of metronidazole and in vitro-in vivo relationships.

    PubMed

    Chien, Y W; Oppermann, J; Nicolova, B; Lambert, H J

    1982-07-01

    The technical feasibility of utilizing tampons as a drug delivery system for prolonged intravaginal drug administrations was studied. Several commercially available brands of tampons were examined. The methodology for the incorporation of various doses of metronidazole, an antitrichomonas agent, in tampons was described. The sustained-release profile of metronidazole from these medicated tampons was characterized. Intravaginal administration of metronidazole via the medicated tampons was investigated in rhesus monkeys and human volunteers, and in vitro-in vivo correlations were established. The biopharmaceutics of intravaginal absorption of metronidazole via medicated tampons was analyzed in comparison with a vaginal solution formulation.

  2. Ex vivo bioadhesion and in vivo testosterone bioavailability study of different bioadhesive formulations based on starch-g-poly(acrylic acid) copolymers and starch/poly(acrylic acid) mixtures.

    PubMed

    Ameye, D; Voorspoels, J; Foreman, P; Tsai, J; Richardson, P; Geresh, S; Remon, J P

    2002-02-19

    Starch-g-poly(acrylic acid) copolymers or grafted starches synthesized by 60Co irradiation or chemical modification and co-freeze-dried starch/poly(acrylic acid) mixtures were evaluated on their ex vivo bioadhesion capacity. The buccal absorption of testosterone from a bioadhesive tablet formulated with the grafted starches or starch/poly(acrylic acid) mixtures was investigated. The results were compared to a reference formulation (physical mixture of 5% Carbopol 974P and 95% Drum Dried Waxy Maize). Rice starch-based irradiated grafted starches showed the best bioadhesion results. Partial neutralization of the acrylic acid with Ca(2+) ions resulted in significantly higher bioadhesion values compared to the reference. Ca(2+) and Mg(2+) partially neutralized maltodextrin-based irradiated grafted starches showed significantly higher bioadhesion values compared to the reference formulation. The chemically modified grafted starches showed significantly higher adhesion force values than for the reference tablet. None of the co-freeze-dried starch/poly(acrylic acid) mixtures showed significantly higher bioadhesion results than the reference (Bonferroni test, P<0.05). A chemically modified grafted starch could sustain the 3 ng/ml plasma testosterone target concentration during +/- 8 h (T(>3 ng/ml)). By lyophilization of a partially neutralized irradiated grafted starch, the in vivo adhesion time (22.0 +/- 7.2 h) and the T(>3 ng/ml) (13.5 +/- 1.3 h) could be increased. The absolute bioavailability of the lyophilized formulation approached the reference formulation. Some of the grafted starches showed to be promising buccal bioadhesive drug carriers for systemic delivery. PMID:11853929

  3. Natural antimicrobials subtilosin and lauramide arginine ethyl ester synergize with conventional antibiotics clindamycin and metronidazole against biofilms of Gardnerella vaginalis but not against biofilms of healthy vaginal lactobacilli.

    PubMed

    Algburi, Ammar; Volski, Anna; Chikindas, Michael L

    2015-07-01

    The purpose of this study was to evaluate the ability of clindamycin and metronidazole to synergize with natural antimicrobials against biofilms of bacterial vaginosis (BV)-associated Gardnerella vaginalis. Minimum bactericidal concentrations for biofilm cells (MBCs-B) were determined for each antimicrobial. The MBCs-B of lauramide arginine ethyl ester (LAE), subtilosin, clindamycin and metronidazole were 50, 69.5, 20 and 500 μg mL(-1), respectively. A checkerboard assay and isobologram were used to analyze the type of interactions between these antimicrobials. The combination of metronidazole with natural antimicrobials did not inhibit planktonic lactobacilli. Clindamycin with either LAE or with subtilosin was inhibitory for planktonic but not for biofilm-associated lactobacilli. All tested antimicrobial combinations were inhibitory for BV-associated Mobiluncus curtisii and Peptostreptococcus anaerobius. LAE and subtilosin synergized with clindamycin and metronidazole against biofilms of G. vaginalis but not biofilm-associated vaginal lactobacilli. The biofilms of BV-associated pathogens can be controlled by synergistically acting combinations of conventional antibiotics and natural antimicrobials which will help better management of current antibiotics, especially considering robust bacterial resistance. Our findings create a foundation for a new strategy in the effective control of vaginal infections.

  4. Formulation of Topical Bioadhesive Gel of Aceclofenac Using 3-Level Factorial Design

    PubMed Central

    Singh, Sanjay; Parhi, Rabinarayan; Garg, Anuj

    2011-01-01

    The objective of this work was to develop bioadhesive topical gel of Aceclofenac with the help of response-surface approach. Experiments were performed according to a 3-level factorial design to evaluate the effects of two independent variables [amount of Poloxamer 407 (PL-407 = X1) and hydroxypropylmethyl cellulose K100 M (HPMC = X2)] on the bioadhesive character of gel, rheological property of gel (consistency index), and in-vitro drug release. The best model was selected to fit the data. Mathematical equation was generated by Design Expert® software for the model which assists in determining the effect of independent variables. Response surface plots were also generated by the software for analyzing effect of the independent variables on the response. Quadratic model was found to be the best for all the responses. Both independent variable (X1 and X2) were found to have synergistic effect on bioadhesion (Y1) but the effect of HPMC was more pronounced than PL-407. Consistency index was enhanced by increasing the level of both independent variables. An antagonistic effect of both independent variables was found on cumulative percentage release of drug in 2 (Y3) and 8 h (Y4). Both independent variables approximately equally contributed the antagonistic effect on Y3 whereas antagonistic effect of HPMC was more pronounced than PL-407. The effect of formulation variables on the product characteristics can be easily predicted and precisely interpreted by using a 3-level factorial experimental design and generated quadratic mathematical equations. PMID:24250375

  5. Physical-mechanical, moisture absorption and bioadhesive properties of hydroxypropylcellulose hot-melt extruded films.

    PubMed

    Repka, M A; McGinity, J W

    2000-07-01

    The objective of this study was to investigate the moisture absorption, physical-mechanical and bioadhesive properties of hot-melt extruded hydroxypropylcellulose (HPC) films containing polymer additives. These additives included polyethylene glycol (PEG) 5%, polycarbophil 5%, carbomer 5%, Eudragit E-100 5%, and sodium starch glycolate (SSG) 5%. Relative humidity (RH) and temperature parameters of the films studied included 25 degree C at 0, 50, 80 and 100% RH, and 40 degrees C at 0 and 100% RH, stored for 2 weeks. Tensile strength and percent elongation were determined on an Instron according to the ASTM standards. The bioadhesive properties of the HPC/PEG 3350 5% film and the polycarbophil 5% containing films, with and without PEG, were investigated in vivo on the human epidermis. Although all films studied exhibited an increase in percent water content as the percent RH increased, the SSG containing film exhibited an almost three-fold increase in percent water content compared to that of the HPC/PEG film. The temperature storage condition of 40 degrees C/100% RH (versus 25 degrees C/100% RH) increased the percent water content of the SSG containing film. Percent elongation was highest for films containing polycarbophil 5% (without PEG). In addition, the HPC film containing polycarbophil 5% exhibited a greater force of adhesion and elongation at adhesive failure in vivo, and a lower modulus of adhesion when compared to the HPC/PEG film. A novel approach to determine bioadhesion of films to the human epidermis is presented.

  6. Temperature Stability and Bioadhesive Properties of Δ9-Tetrahydrocannabinol Incorporated Hydroxypropylcellulose Polymer Matrix Systems

    PubMed Central

    Repka, Michael A.; Munjal, Manish; ElSohly, Mahmoud A.; Ross, Samir A.

    2010-01-01

    The purpose of this study was to determine and compare the bioadhesive profiles of hydroxypropylcellulose (HPC) polymer matrices as a function of Δ9-tetrahydrocannabinol (THC) content. In addition, the effect of processing temperature on the stability of THC and its extent of degradation to cannabinol (CBN) was investigated. A hot-melt cast molding method was used to prepare HPC polymer matrix systems incorporated with THC at 0, 4, 8, and 16 percent. Bioadhesive measurements including peak adhesive force, area under the curve, and elongation at adhesive failure were recorded utilizing the TA.XT2i Texture Analyzer™. Data obtained from these tests at various contact time intervals suggested that the incorporation of THC led to an increase in the bioadhesive strength of the HPC polymer matrices. To determine the stability of THC and the resulting CBN content in the matrices, three different processing temperatures were utilized (120, 160, and 200°C). Post-production High Performance Liquid Chromotography (HPLC) analysis revealed that the processed systems contained at least 94% of THC and the relative percent formation of CBN was 0.5% at 120°C and 0.4% at 160°C compared to 1.6% at 200°C. These findings indicate that the cannabinoid may be a plausible candidate for incorporation into systems utilizing hot-melt extrusion techniques for the development of an effective mucoadhesive transmucosal matrix system for delivery of THC. PMID:16455601

  7. 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.

  8. 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. PMID:27363055

  9. 78 FR 19271 - Draft Guidance for Industry on Bioequivalence Recommendations for Metronidazole Vaginal Gel...

    Federal Register 2010, 2011, 2012, 2013, 2014

    2013-03-29

    ... abbreviated new drug applications (ANDAs) for metronidazole vaginal gel. DATES: Although you can comment on... Research, Food and Drug Administration, 10903 New Hampshire Ave., Bldg. 51, rm. 2201, Silver Spring, MD... the availability of draft BE recommendations for metronidazole vaginal gel. New drug...

  10. Multidisciplinary Analysis of a Nontoxigenic Clostridium difficile Strain with Stable Resistance to Metronidazole

    PubMed Central

    Moura, Ines; Monot, Marc; Tani, Chiara; Barbanti, Fabrizio; Norais, Nathalie; Dupuy, Bruno; Bouza, Emilio; Mastrantonio, Paola

    2014-01-01

    Stable resistance to metronidazole in a nontoxigenic Clostridium difficile strain was investigated at both the genomic and proteomic levels. Alterations in the metabolic pathway involving the pyruvate-ferredoxin oxidoreductase were found, suggesting that reduction of metronidazole, required for its activity, may be less efficient in this strain. Proteomic studies also showed a cellular response to oxidative stress. PMID:24913157

  11. 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

  12. 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.

  13. 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

  14. Formulation and evaluation of different floating tablets containing metronidazole to target stomach.

    PubMed

    Loh, Zhiao C; Elkordy, Amal A

    2015-01-01

    The purpose of this study is to formulate and develop tablets dosage form containing Metronidazole which has swelling and floating properties as a gastroretentive controlled-release drug delivery system to improve drug bioavailability. Fifteen different formulations of effervescence-forming floating systems were designed using HPMC K15M, xanthan gum, co-povidone, Eudragit® RL PO, pluronic® F-127 and/or polypropylene foam powder as swelling agents and sodium bicarbonate with/ without citric acid as gas-forming agents at different compositions. Six out of these 15 formulations which have satisfactory tablet floating behaviour were further studied with the incorporation of Metronidazole. The tablets were evaluated based on tablet physicochemical properties, floating behaviour, swelling ability and drug dissolution studies which were carried out using 0.1M HCl at 37°C for 8 hours. Furthermore, evaluation of the powder mixtures using Fourier transform infrared (FT-IR) spectroscopy, differential scanning calorimetry (DSC) and scanning electron microscope (SEM) were investigated. Most of the tablets show good physicochemical properties except for F11 which contains pluronic® F-127 as its release-retarding matrix-forming polymer. Other formulations show high swelling capacity, ability to float for at least 8 hours in vitro and have sustained drug release characteristics. Data obtained indicated that F3 which contains HPMC (12.5%w/w), xanthan gum (25%w/w), co-povidone (12.5%w/w) and sodium bicarbonate (31.7%w/w) is a suitable formulation with short floating lag time, good floating behaviour and sustained drug release for at least 8 hours in vitro with a zero order kinetic. Combinations of HPMC K15M and xanthan gum as swelling agents show synergistic effect in retarding drug release and are suitable in providing the most sustained drug release system.

  15. 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.

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

    PubMed

    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.

  17. In Vitro Susceptibility of Iranian Isolates of Trichomonas vaginalis to Metronidazole

    PubMed Central

    MATINI, Mohammad; MAGHSOOD, Amir-Hossein; MOHEBALI, Mahdi; RABIEE, Soghra; FALLAH, Mohammad; REZAIE, Sassan; REZAEIAN, Mostafa

    2016-01-01

    Background: Metronidazole, a 5-nitroimidazole derivative, is the main antitrichomonal agent of choice for treatment of trichomoniasis. Since 1962, some cases of treatment failure with metronidazole have been reported and recently drug resistance is now on the rise in the world. This study was aimed to determine current susceptibility of Iranian isolates of Trichomonas vaginalis to metronidazole. Methods: This study was performed on 50 T. vaginalis isolates collected from west and central areas of Iran. After axenisation of the parasites, susceptibility testing was carried out by using serial twofold dilutions of metronidazole (400 to 0.1 μg/ml). The minimum inhibitory concentration (MIC) and the minimum lethal concentration (MLC) of the trichomonads were determined after 48 h incubation at 35.5 °C. Drug susceptibility assays of the all isolates were carried out two times in triplicate under aerobic and anaerobic conditions. Results: Ninety-eight percent of the T. vaginalis isolates (49/50) were sensitive to metronidazole. Metronidazole resistance was defined as aerobic MIC ≥50 μg/ml, detected in one isolate. The means of aerobic MICs and MLCs and that of anaerobic MICs of the parasites were 2.91, 1.95 and 0.28 μg/ml, respectively. Conclusion: This investigation showed in vitro low-level tolerance to metronidazole in a few T. vaginalis isolates that may be leading to the development of drug resistance. PMID:27095968

  18. Percutaneous absorption kinetics of topical metronidazole formulations in vitro in the human cadaver skin model.

    PubMed

    Elewski, Boni E

    2007-01-01

    Topical formulations containing identical active agents are available in various vehicles and concentrations, which may affect percutaneous absorption. This study was undertaken to evaluate the in vitro percutaneous absorption pharmacokinetics of metronidazole in different vehicles and concentrations as the active agent in 6 topical formulations. Formulations were applied to sections from 3 cadaver skin donors, and percutaneous absorption of metronidazole was measured over a 48-h test period through the finite dose technique and the use of Franz diffusion cells. Metronidazole penetrates into and through human cadaver skin. Data show the general ranking of delivery of similar concentrations of metronidazole according to vehicle as cream > lotion > gel. The 48-h penetration of metronidazole in the human cadaver skin model was greatest with cream formulations and lowest with gel formulations. These results reveal the importance of the vehicle selected for penetration of metronidazole into the skin. The relevant target zone in rosacea is the dermis because this is the area where inflammation takes place. Additional studies are warranted to examine absorption of metronidazole into the relevant target zone and the correlation of absorption with efficacy.

  19. 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.

  20. 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

  1. 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.

  2. Mechanisms of selective toxicity of metronidazole and other nitroimidazole drugs.

    PubMed Central

    Edwards, D I

    1980-01-01

    The selectively toxic effect of nitroimidazole drugs towards anaerobic bacteria and protozoa depends on a number of factors. The killing action of such drugs as metronidazole requires the reduction of the nitro group, a process which influences the rate of entry of the drug into the susceptible cell and which is determined by mechanisms involving ferredoxin-linked (or the equivalent) reactions in the cell. The reduced agent subsequently causes strand breakage of DNA, the extent of which depends on the A + T content of the DNA. Other effects of such drugs may include the possible inhibition of DNA repair mechanisms which exacerbate DNA damage, Inhibition of activity of nitroimidazoles may be caused by aminothiol radical scavengers and radioprotectors normally present in the cell or by the presence of other organisms in the environment (that is, the vagina) capable of inactivating the drugs. PMID:7000306

  3. The role of vancomycin and metronidazole for the treatment of Clostridium difficile-associated diarrhea.

    PubMed

    Tart, Serina B

    2013-10-01

    For the treatment of Clostridium difficile-associated diarrhea (CDAD), metronidazole and vancomycin remain the most commonly used agents. The major advantage of metronidazole is its low cost, while the advantage of oral vancomycin is a more favorable pharmacokinetic profile. The epidemiology and clinical severity of CDAD have changed due to the emergence of a hypervirulent strain (BI/NAP1/027). In 2010, the Infectious Diseases Society of America/Society for Health Care Epidemiology of America expert panel defined severe CDAD and recommended oral vancomycin to treat these patients. Metronidazole remains the preferred agent for treatment of mild to moderate CDAD.

  4. Development of a Curcumin Bioadhesive Monolithic Tablet for Treatment of Vaginal Candidiasis.

    PubMed

    Hani, Umme; Shivakumar, H G; Osmani, Riyaz Ali M; Srivastava, Atul; Kumar Varma, Naga Sravan

    2016-01-01

    The present investigation was designed to formulate a natural tablet for the treatment of vaginal candidiasis in order to eliminate side effects that are caused by existing antifungal drugs. Curcumin has promising antifungal activity in comparison with the existing azole antifungal drugs. Bioadhesive curcumin vaginal tablets were prepared by direct compression with different ratios of biadhesive polymers like xanthan gum, guar gum and HPMC. Curcumin tablets were characterized by studies of friability, hardness, hydration, DSC, mucoadhesion, In-vitro release and antifungal activity. DSC and FT-IR data indicate there was no interaction between the drug and the excipients and also polymer concentration has some effects on melting point of curcumin. Formulation F3 showed the best results in terms of swelling and mucoadhesion together with prolonged drug release. The antifungal activity of the Curcumin tablet has demonstrated a significant effect against Candida albicans. Hence, the study indicates the possible and effective use of curcumin bioadhesive monolithic vaginal tablet for vaginal candidiasis as a promising natural antifungal treatment. PMID:27610145

  5. Development of a Curcumin Bioadhesive Monolithic Tablet for Treatment of Vaginal Candidiasis

    PubMed Central

    Hani, Umme; Shivakumar, H.G.; Osmani, Riyaz Ali M.; Srivastava, Atul; Kumar Varma, Naga Sravan

    2016-01-01

    The present investigation was designed to formulate a natural tablet for the treatment of vaginal candidiasis in order to eliminate side effects that are caused by existing antifungal drugs. Curcumin has promising antifungal activity in comparison with the existing azole antifungal drugs. Bioadhesive curcumin vaginal tablets were prepared by direct compression with different ratios of biadhesive polymers like xanthan gum, guar gum and HPMC. Curcumin tablets were characterized by studies of friability, hardness, hydration, DSC, mucoadhesion, In-vitro release and antifungal activity. DSC and FT-IR data indicate there was no interaction between the drug and the excipients and also polymer concentration has some effects on melting point of curcumin. Formulation F3 showed the best results in terms of swelling and mucoadhesion together with prolonged drug release. The antifungal activity of the Curcumin tablet has demonstrated a significant effect against Candida albicans. Hence, the study indicates the possible and effective use of curcumin bioadhesive monolithic vaginal tablet for vaginal candidiasis as a promising natural antifungal treatment. PMID:27610145

  6. Bioadhesive film formed from a novel organic-inorganic hybrid gel for transdermal drug delivery system.

    PubMed

    Guo, Ruiwei; Du, Xiaoyan; Zhang, Rui; Deng, Liandong; Dong, Anjie; Zhang, Jianhua

    2011-11-01

    A novel organic-inorganic hybrid film-forming agent for TDDS was developed by a modified poly(vinyl alcohol) (PVA) gel using γ-(glycidyloxypropyl)trimethoxysilane (GPTMS) as an inorganic-modifying agent, poly(N-vinyl pyrrolidone) (PVP) as a tackifier and glycerol (GLY) as a plasticizer. The prepared gels can be applied to the skin by a coating method and in situ form very thin and transparent films with good performance, comfortable feel and cosmetic attractiveness. The key properties of the bioadhesive films produced from the hybrid gels were investigated and the results showed that the incorporation of appropriate GPTMS (GPTMS/(PVA+GPTMS) in the range of 20-30%) into the PVA matrix not only can significantly enhance mechanical strength and skin adhesion properties of the resultant film, but also can decrease the crystalline regions of PVA and hence facilitate the diffusion of water vapor and drug. Furthermore, the investigations into in vivo skin irritation suggested the films caused non-irritation to skin after topical application for 120 h. In conclusion, the bioadhesive films formed from organic-inorganic hybrid gels possessed very good qualities for application on the skin and may provide a promising formulation for TDDS, especially when the patient acceptability from an aesthetic perspective of the dosage form is a prime consideration. PMID:21723945

  7. Development of a Curcumin Bioadhesive Monolithic Tablet for Treatment of Vaginal Candidiasis

    PubMed Central

    Hani, Umme; Shivakumar, H.G.; Osmani, Riyaz Ali M.; Srivastava, Atul; Kumar Varma, Naga Sravan

    2016-01-01

    The present investigation was designed to formulate a natural tablet for the treatment of vaginal candidiasis in order to eliminate side effects that are caused by existing antifungal drugs. Curcumin has promising antifungal activity in comparison with the existing azole antifungal drugs. Bioadhesive curcumin vaginal tablets were prepared by direct compression with different ratios of biadhesive polymers like xanthan gum, guar gum and HPMC. Curcumin tablets were characterized by studies of friability, hardness, hydration, DSC, mucoadhesion, In-vitro release and antifungal activity. DSC and FT-IR data indicate there was no interaction between the drug and the excipients and also polymer concentration has some effects on melting point of curcumin. Formulation F3 showed the best results in terms of swelling and mucoadhesion together with prolonged drug release. The antifungal activity of the Curcumin tablet has demonstrated a significant effect against Candida albicans. Hence, the study indicates the possible and effective use of curcumin bioadhesive monolithic vaginal tablet for vaginal candidiasis as a promising natural antifungal treatment.

  8. Synthesis and characterization of injectable bioadhesive hydrogels for nucleus pulposus replacement and repair of the damaged intervertebral disc.

    PubMed

    Vernengo, J; Fussell, G W; Smith, N G; Lowman, A M

    2010-05-01

    Bioadhesive polymers are natural or synthetic materials that can be used for soft tissue repair. The aim of this investigation was to develop an injectable, bioadhesive hydrogel with the potential to serve as a synthetic replacement for the nucleus pulposus of the intervertebral disc or as an annulus closure material. Branched copolymers of poly(N-isopropylacrylamide) (PNIPAAm) and poly(ethylene glycol) (PEG) were blended with poly(ethylene imine) (PEI). This three component injectable system can form a precipitated gel at physiological temperature due to the phase transition of PNIPAAm. The injection of glutaraldehyde into the gel core will adhere the implant to the surrounding tissues. (1)H NMR results indicated the successful physical incorporation of PEI into the PNIPAAm-PEG network by blending. In addition, the covalent crosslinking between the amine functionalities on the PEI and the aldehyde functionalities on the glutaraldehyde was verified using FTIR difference spectroscopy. Mechanical characterization of these blends showed a significant increase (p < 0.05) in compressive modulus following glutaraldehyde injection. The in vitro bioadhesive force studies with porcine skin showed a significant increase (p < 0.05) in the mean maximum force of detachment for PNIPAAm-PEG/PEI gels when glutaraldehyde was injected into the gel core. The results of this study indicate that the reactivity between amines and aldehyde functionalities can be exploited to impart bioadhesive properties to PNIPAAm-PEG/PEI copolymers.

  9. In situ gelling, bioadhesive nasal inserts for extended drug delivery: in vitro characterization of a new nasal dosage form.

    PubMed

    Bertram, Ulrike; Bodmeier, Roland

    2006-01-01

    The purpose of this study was the preparation and characterization of sponge-like, in situ gelling inserts based on bioadhesive polymers. Hydrophilic polymers (carrageenan, Carbopol, chitosan, hydroxypropyl methylcellulose (HPMC) K15M and E5, sodium alginate, sodium carboxy methylcellulose (NaCMC), polyvinyl pyrrolidone (PVP) 90, xanthan gum) were dissolved with/without the model drug oxymetazoline HCl in demineralized water and lyophilized into small inserts. The drug release, water uptake, mechanical properties, X-ray diffraction and bioadhesion potential of the nasal inserts were investigated. A sponge-like structure of nasal inserts was formed with amorphous, but not with crystalline polymers during the freeze-drying process. The insert hardness increased with the glass transition temperature of the polymer (PVP25bioadhesion potential was governed by the polymer ability to interact with mucin/agar (highest for carrageenan, Carbopol, xanthan gum and NaCMC). Inserts prepared from low molecular weight polymers resulted in polymer dissolution and fast drug release (HPMC E5, Na-alginate, PVP90). The drug release from inserts prepared from high molecular weight polymers (carrageenan, Carbopol, chitosan, HPMC K15M, NaCMC, xanthan gum) was a complex interplay of osmotic forces, water uptake and electrostatic interactions between drug and polymer. The drug release decreased with higher polymer content and increased drug loading of the insert. Bioadhesive nasal inserts have a high potential as new nasal dosage form for extended drug delivery.

  10. Design and evaluation of an innovative floating and bioadhesive multiparticulate drug delivery system based on hollow structure.

    PubMed

    Zhang, Chungang; Tang, Jingya; Liu, Dechun; Li, Xuetao; Cheng, Lan; Tang, Xing

    2016-04-30

    In this study a gastric-retentive delivery system was prepared by a novel method which is reported here for the first time. An innovative floating and bioadhesive drug delivery system with a hollow structure was designed and prepared. The floating and bioadhesive drug delivery system was composed of a hollow spherical shell, a waterproof layer (Stearic acid), a drug layer (Ofloxacin), a release retarding film (the novel blended coating materials) and a bioadhesive layer (Carbomer 934P) prepared by using a liquid multi-layering process. A novel blended coating material was designed and investigated to solve the problem of the initial burst release of the formulation and the release mechanism of the novel material was analyzed in this study. The optimized formulation provided the sustained release characteristic and was able to float for 24h. The SEM cross-section images showed that the particulates were hollow with a spherical shell. X-ray images and pharmacokinetic studies (Frel = 124.1 ± 28.9%) in vivo showed that the gastric-retentive delivery system can be retained in the stomach for more than 6h. The floating and bioadhesive particulate drug delivery system based on a hollow structure with a dual function presented here is a viable alternative to other for gastroretentive drug delivery system. PMID:26943975

  11. Comparison of salivary fluoride concentrations after administration of a bioadhesive slow-release tablet and a conventional fluoride tablet.

    PubMed

    Bottenberg, P; Cleymaet, R; de Muynck, C; Remon, J P; Coomans, D; Slop, D

    1992-08-01

    The in-vitro and in-vivo fluoride release of bioadhesive, slow-release tablets prepared from a mixture of polyethylene glycol polymers, containing 0.1 mg of fluoride as NaF was studied, and their ability to sustain fluoride levels in saliva were compared with conventional fluoride tablets with the same fluoride content. In-vitro release experiments showed that the bioadhesive tablets needed 8 h to release all their fluoride compared with less than 1 h for the conventional fluoride tablets. In-vivo, the bioadhesive tablets had a retention period of 6 h and could sustain a salivary fluoride level of more than 10 microM above the baseline for 7 h. The conventional fluoride tablets achieved a peak concentration of 0.5 mM directly after dissolution in the mouth, but the fluoride level could not be sustained for longer than 1 h. A good agreement was found between the in-vitro swelling behaviour of the bioadhesive tablets and their in-vitro and in-vivo release characteristics and their in-vivo retention time. PMID:1359097

  12. 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.

  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. PMID:27010257

  14. 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.

  15. 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. PMID:26652358

  16. Effect of different sterilisation methods on the properties of bioadhesive powders and ocular minitablets, and clinical evaluation.

    PubMed

    Weyenberg, W; Vermeire, A; D'Haese, E; Vanhaelewyn, G; Kestelyn, P; Callens, F; Nelis, H J; Remon, J P; Ludwig, A

    2004-09-01

    The purpose of this study was to evaluate the influence of gamma-irradiation and dry heat sterilisation on the properties of a bioadhesive powder mixture containing ciprofloxacin and its corresponding ocular minitablets. The molecular weight characteristics of drum dried waxy maize starch (DDWM), employed as major component of the bioadhesive formulation, the decay kinetics of radicals, the rheological properties of the bioadhesive polymers and the microbial activity of ciprofloxacin were studied. The influence of the different sterilisation methods on the characteristics of the ocular minitablets was investigated by measuring the crushing strength, the friability, and the in vitro release of ciprofloxacin from the minitablets. Finally, the clinical value of the selected sterilised minitablets was evaluated in seven healthy volunteers. Both sterilisation methods similarly affected the properties of the bioadhesive formulation by inducing stable radicals and decreasing the molecular weight of DDWM, although no changes in the microbiological activity of ciprofloxacin were measured. An obvious influence of both sterilisation methods was observed in the in vitro release study. The crushing strength and friability of the minitablets were not significantly influenced by gamma-irradiation. Based on these data, gamma-irradiation was more adequate as sterilisation method for the bioadhesive ocular minitablets than dry heat sterilisation, because it affected the least the physical properties of the minitablets. Therefore, the gamma-sterilised minitablets were selected for an in vivo evaluation in seven volunteers. The concentration of ciprofloxacin in the tear film remained above its MIC value for the most common ocular pathogens for at least 8 h. Consequently, the gamma-irradiated minitablets containing ciprofloxacin can be considered as a promising formulation to treat bacterial keratitis and conjunctivitis. PMID:15324925

  17. Preparation of multiple-unit floating-bioadhesive cooperative minitablets for improving the oral bioavailability of famotidine in rats.

    PubMed

    Zhu, Xuehua; Qi, Xiaole; Wu, Zhenghong; Zhang, Ziwei; Xing, Jiayu; Li, Xiangbo

    2014-09-01

    Abstract The aims of this study were to prepare fine famotidine-containing floating-bioadhesive cooperative minitablets and to investigate the possibility of using those minitablets as a delivery system for promoting the oral bioavailability of famotidine. Nine minitablet formulations were designed using hydroxypropylmethylcellulose (HPMC K4M) as release-retarding polymers, Carbopol 971P as bioadhesive materials and sodium bicarbonate (NaHCO3) as gas formers. The prepared 3 ± 0.02 mm minitablets were evaluated in terms of their swelling ability, floating behavior, bioadhesion test and in vitro release. The optimized minitablets (F6) containing HPMC K4M (50.00%, w/w), Carbopol 971P (10.00%, w/w) and NaHCO3 (10.00%, w/w) were found to float in 1 min and remain lastingly buoyant over a period of 8 h in vitro, with excellent bioadhesive properties (20.81 g) and sustained drug release characteristics (T50% = 46.54%) followed one-order model. In addition, plasma concentration-time profiles from pharmacokinetic studies in rats dosed with minitablets showed 1.62-fold (p < 0.05) increased absorption of famotidine, compared to the market tablets XinFaDing®. These studies demonstrated that the multiple-unit floating-bioadhesive cooperative minitablets may be a promising gastro-retentive delivery system for drugs that play a therapeutic role in the stomach. PMID:24456044

  18. 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

  19. Sensitivity to nitazoxanide among metronidazole resistant Helicobacter pylori strains in patients with gastritis

    PubMed Central

    Baradaran Moghaddam, Ali; Mansouri, Shahla; Alebouyeh, Masoud; Farzi, Nastaran; Bayati, Saeed; Amirmozafari, Nour

    2016-01-01

    Background: In this study, the efficacy of nitazoxanide in the treatment of Helicobacter pylori isolates, which were resistant to metronidazole, was examined. Methods: One hundred twenty two patients who underwent endoscopy examinations at Kasra and Laleh hospitals in Tehran from November 2014 to July 2015 were enrolled. Helicobacter pylori strains were isolated from the patients’ endoscopy biopsies by bacteriological culture. Those bacterial isolates resistant to metronidazole were examined for susceptibility to nitazoxanide. Serial agar dilution method was utilized to determine the minimum inhibitory concentrations for the antibiotics. Results: From 122 gastric biopsy specimens, 55 H. pylori isolates were recovered (45%); of which, 40 (72.7%) were resistant to metronidazole. Comparing the MIC values of nitazoxanide with metronidazole revealed significant differences (p<0.05). The MIC50 and MIC90 values for nitazoxanide and metronidazole were 8 and ≥8μg/ml, and 32 and 64μg/ml, respectively. Conclusion: The high levels of metronidazole resistance suggest that this medication may not be beneficial for first-line therapy in Iran. However, considering the relative effectiveness of nitazoxanide, it may be considered a suitable alternative for patients in Iran. PMID:27683646

  20. 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.

  1. 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.

  2. Sensitivity to nitazoxanide among metronidazole resistant Helicobacter pylori strains in patients with gastritis

    PubMed Central

    Baradaran Moghaddam, Ali; Alebouyeh, Masoud; Farzi, Nastaran; Bayati, Saeed; Amirmozafari, Nour

    2016-01-01

    Background: In this study, the efficacy of nitazoxanide in the treatment of Helicobacter pylori isolates, which were resistant to metronidazole, was examined. Methods: One hundred twenty two patients who underwent endoscopy examinations at Kasra and Laleh hospitals in Tehran from November 2014 to July 2015 were enrolled. Helicobacter pylori strains were isolated from the patients’ endoscopy biopsies by bacteriological culture. Those bacterial isolates resistant to metronidazole were examined for susceptibility to nitazoxanide. Serial agar dilution method was utilized to determine the minimum inhibitory concentrations for the antibiotics. Results: From 122 gastric biopsy specimens, 55 H. pylori isolates were recovered (45%); of which, 40 (72.7%) were resistant to metronidazole. Comparing the MIC values of nitazoxanide with metronidazole revealed significant differences (p<0.05). The MIC50 and MIC90 values for nitazoxanide and metronidazole were 8 and ≥8μg/ml, and 32 and 64μg/ml, respectively. Conclusion: The high levels of metronidazole resistance suggest that this medication may not be beneficial for first-line therapy in Iran. However, considering the relative effectiveness of nitazoxanide, it may be considered a suitable alternative for patients in Iran.

  3. Planar bioadhesive microdevices: a new technology for oral drug delivery

    PubMed Central

    Fox, Cade B.; Chirra, Hariharasudhan D.; Desai, Tejal A.

    2014-01-01

    The oral route is the most convenient and least expensive route of drug administration. Yet, it is accompanied by many physiological barriers to drug uptake including low stomach pH, intestinal enzymes and transporters, mucosal barriers, and high intestinal fluid shear. While many drug delivery systems have been developed for oral drug administration, the physiological components of the gastro intestinal tract remain formidable barriers to drug uptake. Recently, microfabrication techniques have been applied to create micron-scale devices for oral drug delivery with a high degree of control over microdevice size, shape, chemical composition, drug release profile, and targeting ability. With precise control over device properties, microdevices can be fabricated with characteristics that provide increased adhesion for prolonged drug exposure, unidirectional release which serves to avoid luminal drug loss and enhance drug permeation, and protection of a drug payload from the harsh environment of the intestinal tract. Here we review the recent developments in microdevice technology and discuss the potential of these devices to overcome unsolved challenges in oral drug delivery. PMID:25219863

  4. Formulation and characterisation of tetracycline-containing bioadhesive polymer networks designed for the treatment of periodontal disease.

    PubMed

    Jones, David S; Lawlor, Michelle S; Woolfson, A David

    2004-01-01

    This study described the drug release, rheological (dynamic and flow) and textural/mechanical properties of a series of formulations composed of 15% w/w polymethylvinylether-co-maleic anhydride (PMVE-MA), 0-9% w/w polyvinylpyrrolidone (PVP) and containing 1-5% w/w tetracycline hydrochloride, designed for the treatment of periodontal disease. All formulations exhibited pseudoplastic flow with minimal thixotropy. Increasing the concentration of PVP sequentially increased the zero-rate viscosity (derived from the Cross model) and the hardness and compressibility of the formulations (derived from texture profile analysis). These affects may be accredited to increased polymer entanglement and, in light of the observed synergy between the two polymers with respect to their textural and rheological properties, interaction between PVP and PMVE-MA. Increasing the concentration of PVP increased the storage and loss moduli yet decreased the loss tangent of all formulations, indicative of increased elastic behaviour. Synergy between the two polymers with respect to their viscoelastic properties was observed. Increased adhesiveness, associated with increased concentrations of PVP was ascribed to the increasing bioadhesion and tack of the formulations. The effect of increasing drug concentration on the rheological and textural properties was dependent on PVP concentration. At lower concentrations (0, 3% w/w) no effect was observed whereas, in the presence of 9% w/w PVP, increasing drug concentration increased formulation elasticity, zero rate viscosity, hardness and compressibility. These observations were ascribed to the greater mass of suspended drug in formulations containing the highest concentration of PVP. Drug release from formulations containing 6 and 9% PVP (and 5% w/w drug) was prolonged and swelling/diffusion controlled. Based on the drug release, rheological and textural properties, it is suggested that the formulation containing 15% w/w PMVE-MA, 6% w/w PVP and

  5. Prophylactic treatment with a novel bioadhesive gel formulation containing aciclovir and tenofovir protects from HSV-2 infection

    PubMed Central

    Shankar, Gita N.; Alt, Carsten

    2014-01-01

    Objectives Over-the-counter access to an inexpensive, effective topical microbicide could reduce the transmission of HIV and would increase women's control over their health and eliminate the need to obtain their partners' consent for prophylaxis. Chronic infection with herpes simplex virus 2 (HSV-2), also known as human herpes virus 2, has been shown to facilitate HIV infection and speed the progression to immunodeficiency disease. Our objective is to develop a drug formulation that protects against both HSV-2 and HIV infection and adheres to the vaginal surface with extended residence time. Methods We developed a formulation using two approved antiviral active pharmaceutical ingredients, aciclovir and tenofovir, in a novel bioadhesive vaginal delivery platform (designated SR-2P) composed of two polymers, poloxamer 407 NF (Pluronic® F-127) and polycarbophil USP (Noveon® AA-1). The efficacy of the formulation to protect from HSV-2 infection was tested in vitro and in vivo. In addition to its efficacy, it is essential for a successful microbicide to be non-irritating to the vaginal mucosa. We therefore tested our SR-2P platform gel in the FDA gold-standard microbicide safety model in rabbits and also in a rat vaginal irritation model. Results Our studies indicated that SR-2P containing 1% aciclovir and 5% tenofovir protects (i) Vero cells from HSV-2 infection in vitro and (ii) mice from HSV-2 infection in vivo. Our results further demonstrated that SR-2P was not irritating in either vaginal irritation model. Conclusions We conclude that SR-2P containing aciclovir and tenofovir may be a suitable candidate microbicide to protect humans from vaginal HSV-2 infection. PMID:25139839

  6. Interaction of calcium sulfate with xanthan gum: effect on in vitro bioadhesion and drug release behavior from xanthan gum based buccal discs of buspirone.

    PubMed

    Jaipal, A; Pandey, M M; Abhishek, A; Vinay, S; Charde, S Y

    2013-11-01

    Bioadhesive polymers in buccal drug delivery systems play an important role in delivery of therapeutic drug molecules for local and systemic action. Xanthan gum, a GRAS listed natural polymer was used to design buccal discs of buspirone hydrochloride by direct compression method. Effect of calcium sulfate on bioadhesive and drug release behavior of xanthan gum buccal discs was studied. Varying amount of calcium sulfate (0%, 5%, 10%, 20%, 30%, 40% and 50%, w/w) in combination with xanthan gum was used to prepare buccal bioadhesive discs. Increase in calcium sulfate concentration resulted in faster drug release and decreased the bioadhesive strength of the designed discs. Further, in rheological evaluation it was observed that viscosity of xanthan gum gel reduces with increasing concentration of calcium sulfate. Compatibility of drug with various excipients was assessed using DSC and FTIR techniques. PMID:23907052

  7. Toxicologic evaluation of metronidazole with particular reference to carcinogenic, mutagenic, and teratogenic potential.

    PubMed

    Roe, F J

    1983-01-01

    The gastrointestinal tract and nervous system are the main targets for metronidazole toxicity. With the possible exception of certain neurotoxic effects in a few heavily treated patients, all the toxic effects of metronidazole are transient and reversible on withdrawal of the drug. Properly designed tests for embryotoxicity and teratogenicity in rats, rabbits, and mice have produced convincingly negative results, and no adverse effects on the fetus have been observed in women given the drug for trichomoniasis during various stages of pregnancy. The antimicrobial activity of metronidazole is thought to depend on its nitroreduction to form short-lived cytotoxic metabolites capable of reacting with deoxyribonucleic acid. It is therefore perhaps not surprising that metronidazole has been reported to be mutagenic for certain strains of Salmonella typhimurium. Metronidazole gave negative results in the mouse micronucleus test and no increase in sister chromatid exchanges or chromosomal aberrations in cultured human lymphocytes. Prolonged exposure to metronidazole in the treatment of patients with Crohn's disease was not associated with any increase in the frequency of chromosomal aberrations. Prolonged high-dose exposure of mice to metronidazole led to an increased incidence of lung tumors in three separate studies and to a suggestive increase in lymphoreticular neoplasia in female animals in one of the studies. These effects are probably nonspecific, since major effects on the incidence of neoplasms of the same and other kinds have been produced by merely varying the amount of a standard diet that mice consume. A reported excess of liver tumors in rats exposed to metronidazole can be explained by the fact that the authors failed to age standardize their data despite a big and highly significant beneficial effect of the drug on survival. Two carcinogenicity studies in hamsters have given entirely negative results. The follow-up for 10 or more years of 771 women first

  8. Mussel adhesion-employed water-immiscible fluid bioadhesive for urinary fistula sealing.

    PubMed

    Kim, Hyo Jeong; Hwang, Byeong Hee; Lim, Seonghye; Choi, Bong-Hyuk; Kang, Seok Ho; Cha, Hyung Joon

    2015-12-01

    Urinary fistulas, abnormal openings of a urinary tract organ, are serious complications and conventional management strategies are not satisfactory. For more effective and non-invasive fistula repair, fluid tissue adhesives or sealants have been suggested. However, conventional products do not provide a suitable solution due to safety problems and poor underwater adhesion under physiological conditions. Herein, we proposed a unique water-immiscible mussel protein-based bioadhesive (WIMBA) exhibiting strong underwater adhesion which was employed by two adhesion strategies of marine organisms; 3,4-dihydroxy-l-phenylalanine (DOPA)-mediated strong adhesion and water-immiscible coacervation. The developed biocompatible WIMBA successfully sealed ex vivo urinary fistulas and provided good durability and high compliance. Thus, WIMBA could be used as a promising sealant for urinary fistula management with further expansion to diverse internal body applications. PMID:26352517

  9. A model for cell motility on soft bio-adhesive substrates.

    PubMed

    Sarvestani, Alireza S

    2011-02-24

    Mechanical stiffness of bio-adhesive substrates has been recognized as a major regulator of cell motility. We present a simple physical model to study the crawling locomotion of a contractile cell on a soft elastic substrate. The mechanism of rigidity sensing is accounted for using Schwarz's two-spring model Schwarz et al. (2006). The predicted dependency between the speed of motility and substrate stiffness is qualitatively consistent with experimental observations. The model demonstrates that the rigidity dependent motility of cells is rooted in the regulation of actomyosin contractile forces by substrate deformation at each anchorage point. On stiffer substrates, the traction forces required for cell translocation acquire larger magnitude but show weaker asymmetry which leads to slower cell motility. On very soft substrates, the model predicts a biphasic relationship between the substrate rigidity and the speed of locomotion, over a narrow stiffness range, which has been observed experimentally for some cell types. PMID:21106198

  10. Lactate dehydrogenase activity in Bacteroides fragilis group strains with induced resistance to metronidazole.

    PubMed

    Presečki Stanko, Aleksandra; Sóki, Jozsef; Varda Brkić, Dijana; Plečko, Vanda

    2016-06-01

    The aims of this study were to induce in vitro metronidazole resistance in nim-negative Bacteroides fragilis group strains and to determine the lactate dehydrogenase (LDH) activity of the induced strains. A collection of B. fragilis group strains were identified by matrix-assisted laser desorption/ionisation time-of-flight mass spectrometry (MALDI-TOF/MS). Minimum inhibitory concentrations (MICs) for metronidazole were determined by the agar dilution technique. The presence of nim genes was screened by PCR. A sample of 52 nim-negative metronidazole-susceptible strains were selected at random and were exposed to metronidazole in the resistance induction experiment. LDH activity was measured by spectrophotometry. Of the 52 selected strains, 12 (23.1%) acquired resistance to metronidazole. MICs ranged from 8mg/L to 96mg/L. Eight of the twelve induced strains displayed decreased LDH activity, whilst only one expressed a significant increase in LDH activity with LDH values of 49.1U/mg and 222.0U/mg, respectively. In conclusion, in vitro induction of metronidazole resistance could be selected in nim-negative B. fragilis group strains. A statistically significant decrease in LDH activity was in contrast to previous findings in which, underlying higher metronidazole MICs, an increase in LDH activity compensated for the decreased activity of pyruvate-ferredoxin oxidoreductase (PFOR). These findings could be explained if the induction caused only physiological and not genetic changes. We believe that genetic mutations in the B. fragilis strain that demonstrated an emergent increase in LDH activity were responsible for the increased activity. PMID:27436459

  11. Discriminatory bio-adhesion over nano-patterned polymer brushes

    NASA Astrophysics Data System (ADS)

    Gon, Saugata

    Surfaces functionalized with bio-molecular targeting agents are conventionally used for highly-specific protein and cell adhesion. This thesis explores an alternative approach: Small non-biological adhesive elements are placed on a surface randomly, with the rest of the surface rendered repulsive towards biomolecules and cells. While the adhesive elements themselves, for instance in solution, typically exhibit no selectivity for various compounds within an analyte suspension, selective adhesion of targeted objects or molecules results from their placement on the repulsive surface. The mechanism of selectivity relies on recognition of length scales of the surface distribution of adhesive elements relative to species in the analyte solution, along with the competition between attractions and repulsions between various species in the suspension and different parts of the collecting surface. The resulting binding selectivity can be exquisitely sharp; however, complex mixtures generally require the use of multiple surfaces to isolate the various species: Different components will be adhered, sharply, with changes in collector composition. The key feature of these surface designs is their lack of reliance on biomolecular fragments for specificity, focusing entirely on physicochemical principles at the lengthscales from 1 - 100 nm. This, along with a lack of formal patterning, provides the advantages of simplicity and cost effectiveness. This PhD thesis demonstrates these principles using a system in which cationic poly-L-lysine (PLL) patches (10 nm) are deposited randomly on a silica substrate and the remaining surface is passivated with a bio-compatible PEG brush. TIRF microscopy revealed that the patches were randomly arranged, not clustered. By precisely controlling the number of patches per unit area, the interfaces provide sharp selectivity for adhesion of proteins and bacterial cells. For instance, it was found that a critical density of patches (on the order of

  12. Effect of Nitro-Functionalization on the Cross-Linking and Bioadhesion of Biomimetic Adhesive Moiety

    PubMed Central

    2015-01-01

    Dopamine mimics the exceptional moisture-resistant adhesive properties of the amino acid, DOPA, found in adhesive proteins secreted by marine mussels. The catechol side chain of dopamine was functionalized with a nitro-group, and the effect of the electron withdrawing group modification on the cross-linking chemistry and bioadhesive properties of the adhesive moiety was evaluated. Both nitrodopamine and dopamine were covalently attached as a terminal group onto an inert, 4-armed poly(ethylene glygol) (PEG-ND and PEG-D, respectively). PEG-ND and PEG-D exhibited different dependence on the concentration of NaIO4 and pH, which affected the curing rate, mechanical properties, and adhesive performance of these biomimetic adhesives differently. PEG-ND cured instantly and its bioadhesive properties were minimally affected by the change in pH (5.7–8) within the physiological range. Under mildly acidic conditions (pH 5.7 and 6.7), PEG-ND outperformed PEG-D in lap shear adhesion testing using wetted pericardium tissues. However, nitrodopamine only formed dimers, which resulted in the formation of loosely cross-linked network and adhesive with reduced cohesive properties. UV–vis spectroscopy further confirmed nitrodopamine’s ability for rapid dimer formation. The ability for nitrodopamine to rapidly cure and adhere to biological substrates in an acidic pH make it suitable for designing adhesive biomaterials targeted at tissues that are more acidic (i.e., subcutaneous, dysoxic, or tumor tissues). PMID:25495043

  13. 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

  14. A new-generation 5-nitroimidazole can induce highly metronidazole-resistant Giardia lamblia in vitro.

    PubMed

    Dunn, Linda A; Burgess, Anita G; Krauer, Kenia G; Eckmann, Lars; Vanelle, Patrice; Crozet, Maxime D; Gillin, Frances D; Upcroft, Peter; Upcroft, Jacqueline A

    2010-07-01

    The 5-nitroimidazole (NI) compound C17, with a side chain carrying a remote phenyl group in the 2-position of the imidazole ring, is at least 14-fold more active against the gut protozoan parasite Giardialamblia than the 5-NI drug metronidazole (MTR), with a side chain in the 1-position of the imidazole ring, which is the primary drug for the treatment of giardiasis. Over 10 months, lines resistant to C17 were induced in vitro and were at least 12-fold more resistant to C17 than the parent strains. However, these lines had ID(90) values (concentration of drug at which 10% of control parasite ATP levels are detected) for MTR of >200 microM, whilst lines induced to be highly resistant to MTR in vitro have maximum ID(90) values around 100 microM (MTR-susceptible isolates typically have an ID(90) of 5-12.8 microM). The mechanism of MTR activation in Giardia apparently involves reduction to toxic radicals by the activity of pyruvate:ferredoxin oxidoreductase (PFOR) and the electron acceptor ferredoxin. MTR-resistant Giardia have decreased PFOR activity, which is consistent with decreased activation of MTR in these lines, but C17-resistant lines have normal levels of PFOR. Therefore, an alternative mechanism of resistance in Giardia must account for these super-MTR-resistant cells. PMID:20456926

  15. 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.

  16. 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. PMID:26731310

  17. 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.

  18. 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

  19. 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. PMID:26524246

  20. 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.

  1. 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

  2. IPNs from Cyclodextrin:Chitosan Antioxidants: Bonding, Bio-Adhesion, Antioxidant Capacity and Drug Release

    PubMed Central

    Perchyonok, V. Tamara; Grobler, Sias R.; Zhang, Shengmiao

    2014-01-01

    IPNs are unique “alloys” of cross-linked polymers in which at least one network is synthesized and/or cross-linked in the presence of the other. IPNs are also known as entanglements of polymer networks that are ideally held together only by permanent topological interactions. The objectives of this study are to evaluate novel chitosan-based functional drug delivery systems that can be successfully incorporated into “dual action bioactive tooth restorative materials”. These materials should be capable of inducing an improved wound healing prototype. The novel hydrogels will be investigated with respect to the antioxidant capacity of conventional antioxidants, such as resveratrol, β-carotene and propolis, as a designer drug delivery system, with the use of SEM imaging for the characterization of the surfaces, bio-adhesive property, antioxidant capacity, free radical defence, antioxidant, active ingredient stability and reactive features of novel materials. The additional benefit of the site-specific “functional restorative material” for use in dressings to deliver antibiotics to wound sites can provide tissue compatibility and reduced interference with wound healing. The materials were tested using an effective in vitro free radical generation model as functional additive prototypes for further development of “dual function restorative wound healing materials”. We quantified the effects of functional designer biomaterials on the dentin bond strength of a composite and evaluated the bio-adhesive capacity of the materials in the two separate “in vitro” systems. The added benefits of the chitosan/vitamin C/cyclodextrin (CD) host:guest complex-treated hydrogels involved a positive influence on the tetracycline release, increased dentin bond strength, as well as a demonstrated in vitro “built-in” free radical defence mechanism and, therefore, acting as a “proof of concept” for functional multi-dimensional restorative wound healing materials

  3. A Reprofiled Drug, Auranofin, Is Effective against Metronidazole-Resistant Giardia lamblia

    PubMed Central

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

    2013-01-01

    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. PMID:23403423

  4. A comparative study of oral single dose of metronidazole, tinidazole, secnidazole and ornidazole in bacterial vaginosis

    PubMed Central

    Thulkar, Jyoti; Kriplani, Alka; Agarwal, Nutan

    2012-01-01

    Objective: To compare the cure rates of oral single dose of metronidazole (2 g), tinidazole (2 g), secnidazole (2 g), and ornidazole (1.5 g) in cases of bacterial vaginosis. Materials and Methods: This was a prospective, comparative, randomized clinical trial on 344 Indian women (86 women in each group) who attended a gynecology outpatient department with complaint of abnormal vaginal discharge or who had abnormal vaginal discharge on Gynecological examination but they did not complaint of it. For diagnosis and cure rate of bacterial vaginosis, Amsel's criteria were used. Statistical analysis was done by Chi-square test of proportions. The cure rate was compared considering metronidazole cure rate as gold standard. Results: At 1 week, the cure rate of tinidazole and ornidazole was 100% and at 4 weeks, it was 97.7% for both drugs (P<0.001). Secnidazole had cure rate of 80.2% at 4 weeks (P=NS). Metronidazole showed a cure rate of 77.9% at 4 weeks, which is the lowest of all four drugs. Conclusion: Tinidazole and ornidazole have better cure rate as compared to metronidazole in cases of bacterial vaginosis. PMID:22529484

  5. Isolation of a genetic locus associated with metronidazole resistance in Helicobacter pylori.

    PubMed

    Chang, K C; Ho, S W; Yang, J C; Wang, J T

    1997-07-30

    We examined the molecular mechanism of metronidazole resistance by constructing a lambda-Zap II phagemid expression library with genomic DNA from a metronidazole-resistance strain of Helicobacter pylori. Twenty-two clones were found to have elevated MTZ resistances in XLOLR strain of E. coli. Phagemids belonging to the twenty two clones were extracted and then retransformed into the XLOLR strain of E. coli. After MTZ selection, five clones could confer metronidazole resistance consistently. According to Southern hybridization and DNA sequencing, the five clones contained a same locus, recA. In addition, transforming the five clones into BL21 strain of E. coli produced a higher resistance to MTZ. Interestingly, electroporation of one of the five phagemid clones into two MTZ sensitive H. pylori yielded MTZ resistant strains. Comparing amino acid sequence in MTZ resistant with sensitive isolates revealed two point mutations at this locus. Above results suggest that mutation in recA may be associated with metronidazole resistance of H. pylori. PMID:9245734

  6. Bioadhesive vaginal drug delivery of nystatin using a derivatized polymer: Development and characterization.

    PubMed

    Bassi, Pallavi; Kaur, Gurpreet

    2015-10-01

    Increasing incidence of resistance to azole antifungals has highlighted the importance of the use of alternative therapeutic agents such as nystatin for the treatment of vulvovaginal candidiasis. The aim of the present study was to develop and characterize locally acting, film formulation for the treatment of candidiasis using a derivatized natural polymer. Derivatization of natural polymer was carried out in order to introduce anionic character to an otherwise neutral polymer, so as to enhance its interaction with vaginal mucous membrane along with inheriting the biocompatibility and nonirritant characteristics of its parent polymer. A carboxymethyl derivative of fenugreek gum (CMFG) was prepared, and characterized by DSC, FTIR and X-ray diffraction studies. The derivatized gum was found to possess bioadhesive and film forming properties. A 3(2) factorial design was employed to formulate vaginal films and a response surface methodological approach was used to study the effect of formulation variables on film properties. Films containing 5% w/v polymer and 2% v/v glycerol exhibited optimum properties in vitro. The optimized drug loaded formulation was able to release 100% drug over a period of 5h and followed Korsmeyer-Peppas kinetics. It was found to be non-irritant and nontoxic to vaginal mucosa and showed appropriate antifungal properties in vivo. PMID:26235393

  7. Development of hydrocolloid Bi-layer dressing with bio-adhesive and non-adhesive properties.

    PubMed

    Khan, M Iqbal H; Islam, Jahid M M; Kabir, Wasifa; Rahman, Ataur; Mizan, Maria; Rahman, M Fizur; Amin, Jakia; Khan, Mubarak A

    2016-12-01

    Bio-active bi-layer thin film having both bio-adhesive and non-adhesive end composed of polyvinyl alcohol (PVA) and gelatin/chitosan/polyethylene glycol (PEG) blend was developed for biomedical applications especially as an alternative of advanced tissue scaffold. The developed composite film was subjected to mechanical, thermal and physico-chemical characterization such as tensile strength (TS) and elongation at break (Eb), differential scanning calorimetry (DSC), Fourier transform infrared spectroscopy (FTIR), fluid drainage capacity and biocompatibility. Suitable packaging was also selected and stability study and aging test of the composite film were performed after packing. The incorporation of chitosan and PEG into gelatin showed improved mechanical properties of both TS and Eb, which suggested the occurrence of interaction among gelatin, chitosan and PEG molecules in the composite film. The presence of crosslinking as an interaction of above three polymers was also confirmed by FTIR study. Results from the DSC study suggested increased thermal stability after crosslinking. On the other hand, water uptake studies suggested excellent fluid drainage capability and hydro-stability of the composite film. The proposed dressing also showed excellent biocompatibility. Based on the studies related to the performance with confirmed identity, we concluded that our developed bi-layer film is very potential as an ideal wound dressing material. PMID:27612753

  8. Novel bioadhesive hyaluronan-itaconic acid crosslinked films for ocular therapy.

    PubMed

    Calles, J A; Tártara, L I; Lopez-García, A; Diebold, Y; Palma, S D; Vallés, E M

    2013-10-15

    New hyaluronic acid (HA)-itaconic acid (IT) films have been previously synthesized and used as potential topical drug delivery systems (DDS) for ocular administration. In this study we explored homogeneous and heterogeneous crosslinking reactions of HA using glutaraldehyde (GTA) and polyethylene glycol diglycidyl ether (PEGDE) in the presence of IT, a naturally occurring compound that is non-toxic and readily biodegradable. We have studied the morphology, mechanical properties and in vitro biocompatibility between these new materials and ocular surface cells (human corneal epithelial cell line) and evaluated the biopharmaceutical performance of the designed formulations. Although all the synthesized materials exhibited good mechanical properties, the PEGDE modified films exhibited the best biocompatibility, with in vivo assays showing good adhesive performance and minimal irritation. PEGDE films were also tested for their effects in the treatment of intraocular pressure (IOP) in rabbits using timolol maleate (TM) as the model drug. These results may be useful for further design of novel bioadhesive matrix containing drugs by topical application in ophthalmology. PMID:23911915

  9. Evaluation of epirubicin in thermogelling and bioadhesive liquid and solid suppository formulations for rectal administration.

    PubMed

    Lo, Yu-Li; Lin, Yijun; Lin, Hong-Ru

    2014-01-01

    Temperature sensitive Pluronic (Plu) and pH-sensitive polyacrylic acid (PAA) were successfully mixed in different ratios to form in situ gelling formulations for colon cancer therapy. The major formulations were prepared as the liquid and solid suppository dosage forms. Epirubicin (Epi) was chosen as a model anticancer drug. In vitro characterization and in vivo pharmacokinetics and therapeutic efficacy of Epi in six Plu/PAA formulations were evaluated. Our in vitro data indicate that Epi in Plu 14%/PAA 0.75% of both solid and liquid suppositories possess significant cytotoxicity, strong bioadhesive force, long-term appropriate suppository base, sustained release, and high accumulation of Epi in rat rectums. These solid and liquid suppositories were retained in the upper rectum of Sprague-Dawley (SD) rats for at least 12 h. An in vivo pharmacokinetic study using SD rats showed that after rectal administration of solid and liquid suppositories, Epi had greater area under the curve and higher relative bioavailability than in a rectal solution. These solid and liquid suppositories exhibited remarkable inhibition on the tumor growth of CT26 bearing Balb/c mice in vivo. Our findings suggest that in situ thermogelling and mucoadhesive suppositories demonstrate a great potential as colon anticancer delivery systems for protracted release of chemotherapeutic agents.

  10. Monitoring the Long-Term Degradation Behavior of Biomimetic Bioadhesive using Wireless Magnetoelastic Sensor

    PubMed Central

    Lin, Meng-Hsien; Anderson, Jonathan; Pinnaratip, Rattapol; Meng, Hao; Konst, Shari; DeRouin, Andrew J.; Rajachar, Rupak

    2015-01-01

    The degradation behavior of a tissue adhesive is critical to its ability to repair a wound while minimizing prolonged inflammatory response. Traditional degradation tests can be expensive to perform, as they require large numbers of samples. The potential for using magnetoelastic resonant sensors to track bioadhesive degradation behavior was investigated. Specifically, biomimetic poly(ethylene glycol)- (PEG-) based adhesive was coated onto magnetoelastic (ME) sensor strips. Adhesive-coated samples were submerged in solutions buffered at multiple pH levels (5.7, 7.4 and 10.0) at body temperature (37°C) and the degradation behavior of the adhesive was tracked wirelessly by monitoring the changes in the resonant amplitude of the sensors for over 80 days. Adhesive incubated at pH 7.4 degraded over 75 days, which matched previously published data for bulk degradation behavior of the adhesive while utilizing significantly less material (~103 times lower). Adhesive incubated at pH 10.0 degraded within 25 days while samples incubated at pH 5.7 did not completely degrade even after 80 days of incubation. As expected, the rate of degradation increased with increasing pH as the rate of ester bond hydrolysis is higher under basic conditions. As a result of requiring a significantly lower amount of samples compared to traditional methods, the ME sensing technology is highly attractive for fully characterizing the degradation behavior of tissue adhesives in a wide range of physiological conditions. PMID:26087077

  11. Development of mannosylated liposomes for bioadhesive oral drug delivery via M cells of Peyer's patches.

    PubMed

    Pukanud, Pongthep; Peungvicha, Penchom; Sarisuta, Narong

    2009-07-01

    The aim of this study was to develop mannosylated liposomes as bioadhesive carriers for oral drug delivery. Two kinds of acyclovir (ACV)-entrapped mannosylated liposomes, i.e. ManN-ACV-lip and PAM-ACV-lip, were prepared by the use of mannosamine HCl (ManN) and p-aminophenyl-alpha-D-mannopyranoside (PAM), respectively. The mean sizes, drug entrapment efficiency, and loading capacity values of all liposomal formulations were in the ranges of 233-371 nm, 82-95%, and 42-47%, respectively. The mean size of PAM-ACV-lip was significantly smaller than those of conventional ACV liposomes and ManN-ACV-lip due to the more conical packing parameter of mannose-conjugated phospholipid. The mannosylating group grafted into bilayer membrane resulted in a decrease in drug entrapment, owing to competitive binding. The in vitro drug absorptions through everted sacs of mice ileum of both mannosylated ACV liposomes were significantly higher than those of conventional ACV liposomes or suspension.

  12. Evaluation of Epirubicin in Thermogelling and Bioadhesive Liquid and Solid Suppository Formulations for Rectal Administration

    PubMed Central

    Lo, Yu-Li; Lin, Yijun; Lin, Hong-Ru

    2014-01-01

    Temperature sensitive Pluronic (Plu) and pH-sensitive polyacrylic acid (PAA) were successfully mixed in different ratios to form in situ gelling formulations for colon cancer therapy. The major formulations were prepared as the liquid and solid suppository dosage forms. Epirubicin (Epi) was chosen as a model anticancer drug. In vitro characterization and in vivo pharmacokinetics and therapeutic efficacy of Epi in six Plu/PAA formulations were evaluated. Our in vitro data indicate that Epi in Plu 14%/PAA 0.75% of both solid and liquid suppositories possess significant cytotoxicity, strong bioadhesive force, long-term appropriate suppository base, sustained release, and high accumulation of Epi in rat rectums. These solid and liquid suppositories were retained in the upper rectum of Sprague-Dawley (SD) rats for at least 12 h. An in vivo pharmacokinetic study using SD rats showed that after rectal administration of solid and liquid suppositories, Epi had greater area under the curve and higher relative bioavailability than in a rectal solution. These solid and liquid suppositories exhibited remarkable inhibition on the tumor growth of CT26 bearing Balb/c mice in vivo. Our findings suggest that in situ thermogelling and mucoadhesive suppositories demonstrate a great potential as colon anticancer delivery systems for protracted release of chemotherapeutic agents. PMID:24384838

  13. Preparation, in vitro and in vivo evaluation of algino-pectinate bioadhesive microspheres: An investigation of the effects of polymers using multiple comparison analysis.

    PubMed

    Chakraborty, Santanu; Khandai, Madhusmruti; Sharma, Anuradha; Khanam, Nazia; Patra, Ch Niranjan; Dinda, Subas Chandra; Sen, Kalyan Kumar

    2010-09-01

    Ionotropic gelation was used to entrap aceclofenac into algino-pectinate bioadhesive microspheres as a potential drug carrier for the oral delivery of this anti-inflammatory drug. Microspheres were investigated in vitro for possible sustained drug release and their use in vivo as a gastroprotective system for aceclofenac. Polymer concentration and polymer/drug ratio were analyzed for their influence on microsphere properties. The microspheres exhibited good bioadhesive property and showed high drug entrapment efficiency. Drug release profiles exhibited faster release of aceclofenac from alginate microspheres whereas algino-pectinate microspheres showed prolonged release. Dunnet's multiple comparison analysis suggested a significant difference in percent inhibition of paw edema when the optimized formulation was compared to pure drug. It was concluded that the algino-pectinate bioadhesive formulations exhibit promising properties of a sustained release form for aceclofenac and that they provide distinct tissue protection in the stomach.

  14. Primary and secondary clarithromycin, metronidazole, amoxicillin and levofloxacin resistance to Helicobacter pylori in southern Poland.

    PubMed

    Karczewska, Elżbieta; Wojtas-Bonior, Izabela; Sito, Edward; Zwolińska-Wcisło, Małgorzata; Budak, Alicja

    2011-01-01

    The aim of this study was to assess the primary and secondary resistance of H. pylori strains cultured from adult patients of the Małopolska region of Poland, mainly of Kraków and the surrounding areas, to antibacterial agents (amoxicillin, clarithromycin, metronidazole and levofloxacin). In total, 115 H. pylori strains were isolated, of which 90 strains originated from patients who had never been treated for H. pylori infection, while the remaining 25 were isolated from patients in whom eradication of the infection failed after treatment. All tested H. pylori strains were susceptible to amoxicillin. Forty-four percent of strains isolated were resistant to metronidazole. The primary and secondary resistance to this antimicrobial chemotherapeutic reached 37% and 72% (p = 0.002), respectively. In total, 34% of strains were resistant to clarithromycin, and the ratio of strains with secondary resistance was significantly greater than that of the strains with primary resistance (80% vs. 21%, p < 0.001). The double resistance to both metronidazole and clarithromycin was confirmed in 23% of H. pylori strains. Five percent of H. pylori strains were resistant to levofloxacin, while primary and secondary resistance to this drug accounted for 2% and 16% (p = 0.006), respectively. In total, 4% of H. pylori strains were simultaneously resistant to metronidazole, clarithromycin and levofloxacin. Thus, the high resistance to metronidazole and clarithromycin excludes the possibility of using these drugs for treatment of H. pylori infection without earlier antibiogramming. Levofloxacin, as a drug of high efficacy against H. pylori, should be reserved for an "emergency" therapy and used in a limited capacity in order to preserve its potent antimicrobial activity. The Polish Society of Gastroenterology recommends levofloxacin as a third-line therapy.

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

    PubMed Central

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

    2015-01-01

    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. PMID:26195522

  16. 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.

  17. Herb-Drug Interaction: A Case Study of Effect of Ginger on the Pharmacokinetic of Metronidazole in Rabbit

    PubMed Central

    Okonta, J. M.; Uboh, M.; Obonga, W. O.

    2008-01-01

    The effect of ginger on the pharmacokinectic of metronidazole was studied using rabbits in a crossover study method. The relevance of this study borders on the wide use of ginger for culinary and phytotherapeutic purposes, and metronidazole that is commonly used for every gastrointestinal complain in our communities without prescription. Ginger significantly increased the absorption and plasma half-life, and significantly decreased the elimination rate constant and clearance of metronidazole (P<0.05). Thus, in clinical practice, the patients should be advised on the serious implication of using both items together. PMID:20046719

  18. A Case Report of Metronidazole Induced Neurotoxicity in Liver Abscess Patient and the Usefulness of MRI for its Diagnosis

    PubMed Central

    Agarwal, Arjit; Shukla, Arvind; Joon, Pawan

    2016-01-01

    Metronidazole is a very widely used drug for the treatment of multiple ailments caused by anaerobic bacteria as well as some protozoan parasites. Though its usual side effects are not very serious, yet sometimes it may cause profound adverse effects like neurotoxicity. We present here a case of liver abscess. The patient was treated for a long time with metronidazole and developed sudden onset neurotoxicity which was diagnosed by MRI. The present case also highlights the need of vigilant monitoring of patients on metronidazole for symptoms of neurotoxicity and the usefulness of MRI for diagnosis of the same. PMID:26894145

  19. [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

  20. A randomized comparative study of sulbactam plus ampicillin vs. metronidazole plus cefotaxime in the management of acute appendicitis in children.

    PubMed

    Foster, M C; Kapila, L; Morris, D L; Slack, R C

    1986-01-01

    Sulbactam is a beta-lactamase inhibitor that, when combined with ampicillin, gives the latter antibiotic a broad spectrum of activity, making it suitable for use as a prophylactic agent in acute appendicitis. In a single-blind, randomized trial, the efficacy of sulbactam plus ampicillin was compared with that of metronidazole plus cefotaxime. Thirty-five children undergoing appendectomy received intravenous sulbactam and ampicillin, while 38 children received metronidazole and cefotaxime. Single doses were given unless the appendix was considered gangrenous or perforated, in which case the drugs were administered for 72 hr. There were three wound infections in the group given sulbactam and ampicillin and five in the group given metronidazole and cefotaxime. The combination of sulbactam and ampicillin was well tolerated and appeared to be at least as effective as that of metronidazole and cefotaxime in the prevention of sepsis following appendectomy. PMID:3026017

  1. In vitro activity of amoxicillin, clindamycin, doxycycline, metronidazole, and moxifloxacin against oral Actinomyces.

    PubMed

    LeCorn, Demetrick W; Vertucci, Frank J; Rojas, Maria F; Progulske-Fox, Ann; Bélanger, Myriam

    2007-05-01

    Actinomyces spp have been increasingly associated with endodontic infections. However, the antimicrobial susceptibility of this genus has not been studied extensively. The objective of this study was to determine the susceptibility of oral isolates of Actinomyces naeslundii, Actinomyces gerencseriae, Actinomyces israelii, Actinomyces viscosus, and Actinomyces odontolyticus to amoxicillin, clindamycin, doxycycline, metronidazole, and moxifloxacin using in vitro assays. The minimum inhibitory concentration (MIC) of each bacterial isolate was determined by using E-test strips (AB Biodisk, Solna, Sweden). The MIC(90) was 0.19 microg/mL for amoxicillin, 0.25 microg/mL for doxycycline, 0.50 microg/mL for moxifloxacin, and 1.00 microg/mL for clindamycin. However, metronidazole was not active against any of the Actinomyces spp tested (MIC(90)>256 microg/mL).

  2. 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.

  3. Metronidazole- and carbapenem-resistant bacteroides thetaiotaomicron isolated in Rochester, Minnesota, in 2014.

    PubMed

    Sadarangani, Sapna P; Cunningham, Scott A; Jeraldo, Patricio R; Wilson, John W; Khare, Reeti; Patel, Robin

    2015-07-01

    Emerging antimicrobial resistance in members of the Bacteroides fragilis group is a concern in clinical medicine. Although metronidazole and carbapenem resistance have been reported in Bacteroides thetaiotaomicron, a member of the B. fragilis group, they have not, to the best of our knowledge, been reported together in the same B. thetaiotaomicron isolate. Herein, we report isolation of piperacillin-tazobactam-, metronidazole-, clindamycin-, ertapenem-, and meropenem-resistant B. thetaiotaomicron from a patient with postoperative intra-abdominal abscess and empyema. Whole-genome sequencing demonstrated the presence of nimD with at least a portion of IS1169 upstream, a second putative nim gene, two β-lactamase genes (one of which has not been previously reported), two tetX genes, tetQ, ermF, two cat genes, and a number of efflux pumps. This report highlights emerging antimicrobial resistance in B. thetaiotaomicron and the importance of identification and antimicrobial susceptibility testing of selected anaerobic bacteria.

  4. [Using Metronidazole and Hydroxyapatite for preventing dry socket after extraction of impacted mandibular 3rd molar

    PubMed

    Xue, Z X; Mao, T Q

    1993-03-01

    Dry socket is one of the most frequent complications after teeth extraction,especially in impacted mandibular third molars.The etilogy and prevention is not clear.This study id based on principles of clinical epidemiology.Randomized double-blind method was carried out in 549 patients to test the value of the prophylactic use of Hydroxyapatite,to test the value of the prophylactic use of Hydroxyapatite and Metronidazole,placed in the sockets of extracted impacted mandibular third molars.The results of the incidence of DS was 7.1% of Metronidazole treated sockets,and 2.1% of Hydroxyapatite treated sockets,It is concluded that Hydroxyapatite is an effective preventive factor for dry socket,The possible mechanism of Hydroxyapatite and the dry socket etiology were discussed. PMID:15159869

  5. 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. PMID:25937011

  6. 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.

  7. 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. PMID:27463556

  8. 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.

  9. 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

  10. 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.

  11. 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. PMID:26481491

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

    PubMed

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

    2016-06-01

    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

  13. 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.

  14. Use of Trichomonas vaginalis clinical isolates to evaluate correlation of gene expression and metronidazole resistance.

    PubMed

    Mead, J R; Fernadez, M; Romagnoli, P A; Secor, W E

    2006-02-01

    We investigated whether variations in gene expression of enzymes associated with anaerobic resistance of laboratory-derived strains of Trichomonas vaginalis could be detected in a group of 28 clinical isolates with variations in metronidazole sensitivity. We compared isolates by real-time PCR because this method allows for highly sensitive quantification of mRNA and for evaluation of several genes simultaneously. We found that PFOR gene A mRNA levels were highly correlated with PFOR gene B levels, as well as the D subunit of malic enzyme and ferrodoxin. Ferrodoxin mRNA expression was also significantly correlated with that of malic enzyme and hydrogenase. However, when we evaluated relationships between these enzymes and resistance to metronidazole, we found no significant correlations between aerobic or anaerobic in vitro sensitivity to drug and mRNA levels of any of the enzymes tested. Similarly, using a Student's t-test, no significant differences in enzyme mRNA levels were observed between isolates separated by metronidazole resistance or susceptibility. The lack of correlation between gene expression and resistance or susceptibility could be the result of differences in expression at the protein level or because other biochemical pathways or genes are involved in the resistance observed in clinical settings. PMID:16629339

  15. Influence of oral metronidazole on the endocrine milieu and sebum excretion rate.

    PubMed

    Aizawa, H; Niimura, M; Kon, Y

    1992-12-01

    As part of a study of the mechanism of metronidazole's efficacy in the treatment of acne and rosacea, its effects on the endocrine milieu and sebum excretion rate were assessed. Thirteen healthy males received oral metronidazole treatment (500 mg/day) for 4 weeks. Serum sex hormone levels were determined in all 13 subjects and the sebum excretion rate was determined in seven of them, before and after treatment. We measured serum levels of estrone (E1), estradiol (E2), total testosterone (T), free testosterone (FT), dihydrotestosterone (DHT), dehydroepiandrosterone sulfate (DHEA-S), and sex hormone-binding globulin (SHBG). There were no significant changes in E1, T, FT, DHT, or SHBG levels, but E2 and DHEA-S levels decreased significantly after treatment. In all seven subjects in whom the sebum excretion rates were determined, the amount of facial skin surface lipids decreased significantly after treatment. These results suggest that metronidazole exerts its clinical effects through suppressing the sebum excretion by a mechanism other than anti-androgenic action. PMID:1293188

  16. Comparative clinical trial of mebendazole and metronidazole in giardiasis of children.

    PubMed

    Sadjjadi, S M; Alborzi, A W; Mostovfi, H

    2001-06-01

    Giardiasis and soil-transmitted helminthosis are prevalent in many parts of the world. Application of a single drug for treatment of both giardiasis and soil-transmitted helminthosis is highly desirable. One hundred children of both sexes, ranging from 7 to 12 years old with Giardia intestinalis cysts or trophozoites in their stool samples, were randomly separated into two groups of 50 individuals each. Each group received either mebendazole tablets 200 mg thrice daily for 5 days or metronidazole tablet 15 mg/kg/day in three divided doses, for 7 days. The results were evaluated by microscopic examination of stools on two successive occasions: 1 week and 2 weeks after treatment. Each occasion consisted of three stool examination on 3 successive days. The cure rate of mebendazole-treated children was 43 out of 50 (86 per cent), and for metronidazole it was 45 out of 50 (90 per cent) with no statistical difference between the two groups. No side-effects were observed in the mebendazole-treated group, whereas nausea, anorexia and metallic taste were observed in 4.9, 6 and 24 per cent of metronidazole-treated children, respectively. In conclusion, the use of mebendazole, which is less toxic with no side-effects, is available and effective on Giardia intestinalis as well as intestinal nematodes, is recommended especially in the areas where giardiasis and intestinal nematodiasis are prevalent and overlap.

  17. 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

  18. [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

  19. [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

  20. Natural Bioadhesive Biodegradable Nanoparticle-Based Topical Ophthalmic Formulations for Management of Glaucoma

    PubMed Central

    Ibrahim, Mohammed Mostafa; Abd-Elgawad, Abd-Elgawad Helmy; Soliman, Osama Abd-Elazeem; Jablonski, Monica M.

    2015-01-01

    Purpose: We prepared and characterized topical ophthalmic formulations containing brimonidine-loaded bioadhesive cationic chitosan or anionic alginate nanoparticles (NPs) for sustained release of brimonidine as once daily regimen for management of glaucoma. Methods: Nanoparticles were prepared using a spontaneous emulsification solvent diffusion method. Different concentrations of polymers, emulsifiers, and NPs stabilizers were used for formulation optimization. Nanoparticles were characterized regarding particle size, zeta potential, morphology, and drug content. Brimonidine-loaded NPs were incorporated into eye drops, a temperature-triggered in situ gelling system, and a preformed gel. They then were characterized regarding their pH, viscosity, uniformity of drug content, in vitro release characteristics, in vitro cytotoxicity, and in vivo intraocular pressure (IOP) lowering effects. Results: Characteristics of optimized brimonidine-loaded chitosan and alginate NPs, respectively, are: particle size, 115.67 ± 3.58 and 157.67 ± 5.53 nm; zeta potential, +35.27 ± 3.39 and −37.8 ± 3.77 mV; encapsulation efficiency, 74.34% ± 2.05% and 70.40% ± 2.77%; drug loading, 11.81% ± 0.67% and 13.14% ± 0.90%; and yield, 87.91% ± 5.92% and 76.53% ± 3.32%. Transmission electron microscope (TEM) analyses revealed that NPs have spherical shapes with a dense core and distinct coat. Formulations possessed uniform drug content. Furthermore, pH and viscosity were compatible with the eye. Formulations showed a sustained release without any burst effect with a Higuchi non-Fickian diffusion mechanism. Cytotoxicity studies revealed that all formulations are biocompatible. Importantly, all formulations possessed a sustained IOP lowering effect compared to the marketed brimonidine tartrate eye drops. Conclusions: These formulations provide a great improvement in topical ocular brimonidine delivery. The application of a single drop is sufficient to provide extended IOP reduction

  1. Design of novel bioadhesive materials based on mussel-derived glues

    NASA Astrophysics Data System (ADS)

    Lee, Bruce Po-Shu

    2005-11-01

    mechanical tests of DOPA-modified gels submerged in an aqueous medium demonstrated strong adhesive interaction to TiO 2, and it was confirmed that the reduced form of DOPA was responsible for the adhesion. This thesis work addressed several needs in the development of novel bioadhesive materials with improved properties in an effort to bring them closer for clinical applications.

  2. Bioadhesive characterization of poly(methylidene malonate 2.12) microparticle on model extracellular matrix.

    PubMed

    Chan, Vincent; Liu, Kuo-Kang; Le Visage, Catherine; Ju, Bin-Feng; Leong, Kam W

    2004-08-01

    The efficacy of a drug delivery system is predicated on its retention in the target tissue. Microparticle is one of the most popular and effective drug delivery configurations. Recently, it has been shown that the interaction between drug-loaded microparticles and tissues is related to the effectiveness of paclitaxel delivery to the bladder wall of mice for treating superficial bladder cancer. In this study, the adhesive interaction between poly(methylidene malonate 2.12) or PMM 2.1.2 microparticles and collagen, which serves as the model extracellular matrix for bladder wall, was probed with confocal reflectance interference contrast microscopy (C-RICM), single-particle compressive force measurement and contact mechanics theory. Young's modulus of single PMM 2.1.2 microparticle was determined as 1.56 +/- 0.25 x 10(4)N/m(2). For plain PMM 2.1.2 microparticle in water (pH 5.5), the degree of deformation (a/R) on collagen coated substrate decreased from 0.77 to 0.26 against the increase of mid-plane diameter from 2 to 18 microm. The adhesion energy of PMM 2.1.2 microparticle was determined from Maguis-JKR theory and remained at around 1.5 mJ/m(2) against the increase of particle diameter. At pH 4, the average degree of particle deformation and adhesion energy was increased by 11% and 32%, respectively, in comparison with that at pH 5.5. The loading of paclitaxel in PMM 2.1.2 microspheres enhanced the deformation and adhesion of microspheres at pH 5.5. It is hypothesized that the electrostatic repulsion between paclitaxel and collagen at pH 4 reduces the adhesion energy of PMM 2.1.2-paclitaxel microsphere. This study may offer insight for design of future microparticulate delivery systems by providing the experimental and theoretical tools to study the bioadhesive interaction between drug-loaded microparticles and model extracellular matrices.

  3. [Preclinical investigation and standardization of metronidazole soft dosage forms].

    PubMed

    Abramovich, R A; Koshelev, Iu A; Vaganova, O A; Elagina, I A

    2005-01-01

    Comparative acute and subacute toxicity of Dentamet gel and Metrovagin suppositories manufactured by ZAO Altaivitaminy was studied with using analogous drugs, i. e. Metrogil Denta, a gel for the gingivae, manufactured by Unique Pharmaceutical Laboratories (India), and Flagil manufactured by Haupt Farma Livron (France) as the reference drugs. It was shown that the drugs induced no changes in the exterior, hair state, body weight and mobility of the experimental animals vs. the control. The pharmacokinetic study of Metrovagin vaginal suppositories vs. the registered analogous drug Flagil showed that Metrovagin was bioequivalent to Flagil. The relative bioavailability of the new drug vs. the control was 103.13%.

  4. 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.

  5. 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. PMID:22186332

  6. DESIGN AND EVALUATION OF A METRONIDAZOLE CENTRAL CORE MATRIX TABLET

    PubMed Central

    Nagaich, Upendra; Chaudhary, Vandana; Tonpay, S.D.; Karki, Roopa

    2010-01-01

    In this paper, a study of different concentration of HPMC K 15 M exerts influence on the drug release process from a new controlled drug delivery system has been realized in order to obtain a constant release rate during a prolonged period of time, for a programmed drug release. The drug release profiles obtained for the different batches have shown an interesting relationship between the particle size of the channeling agent used and the length of different operational periods. PMID:22247836

  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. Influence of metronidazole particle properties on granules prepared in a high-shear mixer-granulator.

    PubMed

    Di Martino, Piera; Censi, Roberta; Malaj, Ledjan; Martelli, Sante; Joiris, Etienne; Barthélémy, Christine

    2007-02-01

    Metronidazole is a good example of high-dose drug substance with poor granulating and tableting properties. Tablets are generally produced by liquid granulation; however, the technological process failure is quite frequent. In order to verify how the metronidazole particle characteristics can influence granule properties, three metronidazole batches differing for crystal habit, mean particle size, BET surface area and wettability were selected, primarily designed according to their different elongation ratio: needle-shaped, stick-shaped, and isodimensional. In the presence of lactose monohydrate and pregelatinized maize starch, respectively as diluent and binder, they were included in a formula for wet granulation in a high-shear mixer-granulator. In order to render the process comparable as far as possible, all parameters and experimental conditions were maintained constant. Four granule batches were obtained: granules from placebo (G-placebo), granules from needle-shaped crystals (G-needle-shaped), granules from stick-shaped crystals (G-stick-shaped), and granules from isodimensional crystals (G-isodimensional). Different granule properties were considered, in particular concerning porosity, friability, loss on drying (LOD), and flowability. In order to study their tabletability and compressibility, the different granules obtained were then compressed in a rotary press. The best tabletability was obtained with the isodimensional batch, while the poorest was exhibited by the stick-shaped one. Differences in tabletability are in good accordance with compressibility results: to a better tabletability corresponds an important granule ability to undergo a volume reduction as a result of an applied pressure. In particular, it was proposed that the greatest compressibility of the G-isodimensional must be related to the greatest granule porosity percentage. PMID:17454043

  9. Double-blind test of metronidazole and tinidazole in the treatment of asymptomatic Entamoeba histolytica and Entamoeba hartmanni carriers.

    PubMed

    Spillmann, R; Ayala, S C; Sanchez, C E

    1976-07-01

    One hundred and fifteen persons with asymptomatic Entamoeba histolytica or E. hartmanni infection, or both, were given metronidazole (750 mg three times daily for 5 days), tinidazole (1 g twice daily on 2 consecutive days), or a starch placebo. Three post-treatment stools were examined in the 2 weeks following initiation of treatment. Cysts of E. histolytica reappeared in the stools of 37% of 30 given metronidazole, 62% of 34 given tinidazole, and 70% of 31 given placebo. Cysts of E. hartmanni reappeared in the stools of 46% of 24 given metronidazole, 69% of 16 given tinidazole, and 90% of 10 given placebo. Rapid absorption and short duration of treatment make both drugs ineffective for the treatment of ameba carriers. PMID:183554

  10. Trichomonas vaginalis: metronidazole and other nitroimidazole drugs are reduced by the flavin enzyme thioredoxin reductase and disrupt the cellular redox system. Implications for nitroimidazole toxicity and resistance.

    PubMed

    Leitsch, David; Kolarich, Daniel; Binder, Marina; Stadlmann, Johannes; Altmann, Friedrich; Duchêne, Michael

    2009-04-01

    Infections with the microaerophilic parasite Trichomonas vaginalis are treated with the 5-nitroimidazole drug metronidazole, which is also in use against Entamoeba histolytica, Giardia intestinalis and microaerophilic/anaerobic bacteria. Here we report that in T. vaginalis the flavin enzyme thioredoxin reductase displays nitroreductase activity with nitroimidazoles, including metronidazole, and with the nitrofuran drug furazolidone. Reactive metabolites of metronidazole and other nitroimidazoles form covalent adducts with several proteins that are known or assumed to be associated with thioredoxin-mediated redox regulation, including thioredoxin reductase itself, ribonucleotide reductase, thioredoxin peroxidase and cytosolic malate dehydrogenase. Disulphide reducing activity of thioredoxin reductase was greatly diminished in extracts of metronidazole-treated cells and intracellular non-protein thiol levels were sharply decreased. We generated a highly metronidazole-resistant cell line that displayed only minimal thioredoxin reductase activity, not due to diminished expression of the enzyme but due to the lack of its FAD cofactor. Reduction of free flavins, readily observed in metronidazole-susceptible cells, was also absent in the resistant cells. On the other hand, iron-depleted T. vaginalis cells, expressing only minimal amounts of PFOR and hydrogenosomal malate dehydrogenase, remained fully susceptible to metronidazole. Thus, taken together, our data suggest a flavin-based mechanism of metronidazole activation and thereby challenge the current model of hydrogenosomal activation of nitroimidazole drugs. PMID:19415801

  11. The flavin inhibitor diphenyleneiodonium renders Trichomonas vaginalis resistant to metronidazole, inhibits thioredoxin reductase and flavin reductase, and shuts off hydrogenosomal enzymatic pathways.

    PubMed

    Leitsch, David; Kolarich, Daniel; Duchêne, Michael

    2010-05-01

    Infections with the microaerophilic protozoan parasite Trichomonas vaginalis are commonly treated with metronidazole, a 5-nitroimidazole drug. Metronidazole is selectively toxic to microaerophiles and anaerobes because reduction at the drug's nitro group, which is a precondition for toxicity, occurs only quantitatively in these organisms. In our previous work we identified the flavin enzyme thioredoxin reductase as an electron donor to 5-nitroimidazole drugs in T. vaginalis and observed that highly metronidazole-resistant cell lines lack thioredoxin reductase and flavin reductase activities. In this study we added the flavin inhibitor diphenyleneiodonium (DPI) to T. vaginalis cultures in order to test our hypothesis that metronidazole reduction is catalyzed by flavin enzymes, e.g. thioredoxin reductase, and intracellular free flavins. Indeed, within hours, DPI rendered T. vaginalis insensitive to metronidazole concentrations as high as 1mM and prevented the formation of metronidazole adducts with proteins. Thioredoxin reductase activity was absent from DPI-treated cells and flavin reductase activity was sharply decreased. In addition, DPI-treated cells also upregulated the expression of antioxidant enzymes, i.e. thioredoxin peroxidases and superoxide dismutases, and displayed a fundamentally altered metabolism caused by inactivation of pyruvate:ferredoxin oxidoreductase (PFOR) and concomitant upregulation of lactate dehydrogenase (LDH) activity. Thus, the disruption of the cellular flavin metabolism by DPI mediated metabolic steps which are similar to that of cells with metronidazole resistance induced in vitro. Finally, we present direct evidence that the increased expression of antioxidant enzymes is dispensable for acquiring resistance to metronidazole. PMID:20093143

  12. Influence of processing parameters and formulation factors on the bioadhesive, temperature stability and drug release properties of hot-melt extruded films containing miconazole.

    PubMed

    Chen, Meiwan; Lu, Jiannan; Deng, Weibin; Singh, Abhilasha; Mohammed, Noorullah Naqvi; Repka, Michael A; Wu, Chuanbin

    2014-06-01

    This study investigated the processing parameters and formulation factors on the bioadhesive properties, temperature stability properties, and drug release properties of miconazole in PolyOx® and Klucel® matrix systems produced by Hot-melt Extrusion (HME) technology. Miconazole incorporated into these matrix systems were found to be stable for 8 months by X-ray diffraction (XRD). The addition of miconazole increased area under the curve (AUC) at contact time intervals of 30 and 60 sec, while the bioadhesion decreased with an increase in processing temperatures. The release profiles suggest that a sustained release of miconazole was observed from all of the tested HME film formulations for approximately 10 h. The release from the optimal HME film extruded at 205°C was found to be significantly different than that extruded at 190°C. Therefore, this matrix system may address the present shortcomings of currently available therapy for oral and pharyngeal candidiasis.

  13. Eradication of H. pylori infection in patients allergic to penicillin using triple therapy with a PPI, metronidazole and sitafloxacin.

    PubMed

    Furuta, Takahisa; Sugimoto, Mitsushige; Yamade, Mihoko; Uotani, Takahiro; Sahara, Shu; Ichikawa, Hitomi; Kagami, Takuma; Yamada, Takanori; Osawa, Satoshi; Sugimoto, Ken; Watanabe, Hiroshi; Umemura, Kazuo

    2014-01-01

    Eradication of H. pylori in patients allergic to penicillin should be performed using regimens without penicillin derivatives. We treated a total of 28 patients allergic to penicillin with a proton pump inhibitor (PPI), metronidazole (250 mg bid) and sitafloxacin (100 mg bid) for one to two weeks. At four to eight weeks after the treatment, the patients underwent the [(13)C]-urea breath test. The overall eradication rate was 100.0%. Mild adverse events were observed. Triple therapy with a PPI, metronidazole and sitafloxacin is well tolerated and effective for the eradication of H. pylori in patients allergic to penicillin. PMID:24633026

  14. [Comparative study for the evaluation of the efficacy and safety of metronidazole and secnidazole in the treatment of vaginal trichomoniasis].

    PubMed

    Buitrón García Figueroa, R; Gonzalo Butrón López, F; Oropez Rechy, G; Romero-Cabello, R

    1997-11-01

    Presently study included 3 groups of 20 women with tricomoniasis demonstrated parasitologicaly for oozing vaginal, the first group received treatment with vaginal ova with metronidazol for 10 days, the second group ova of secnidazol for 3 days and the third group ova of secnidazol for 7 days. The results showed that the clinical manifestations dimanished significantly and the presence of Trichomonas vaginalis disappeared from the vaginal cavity, therefore cure was achieved parasitological in all the cases. We concluded that they are equally useful the metronidazol for 10 days, and the secnidazol for 3 or 7 days, without the presence of adverse effects. PMID:9441152

  15. Scraping and Stapling of End-Grafted DNA Chains by a Bioadhesive Spreading Vesicle to Reveal Chain Internal Friction and Topological Complexity

    NASA Astrophysics Data System (ADS)

    Nam, Gimoon; Hisette, Marie Laure; Sun, Yuting Liang; Gisler, Thomas; Johner, Albert; Thalmann, Fabrice; Schröder, André Pierre; Marques, Carlos Manuel; Lee, Nam-Kyung

    2010-08-01

    Stained end-grafted DNA molecules about 20μm long are scraped away and stretched out by the spreading front of a bioadhesive vesicle. Tethered biotin ligands bind the vesicle bilayer to a streptavidin substrate, stapling the DNAs into frozen confinement paths. Image analysis of the stapled DNA gives access, within optical resolution, to the local stretching values of individual DNA molecules swept by the spreading front, and provides evidence of self-entanglements.

  16. Development of an ex vivo retention model simulating bioadhesion in the oral cavity using human saliva and physiologically relevant irrigation media.

    PubMed

    Madsen, Katrine D; Sander, Camilla; Baldursdottir, Stefania; Pedersen, Anne Marie L; Jacobsen, Jette

    2013-05-20

    In recent years, there has been a particular interest in bioadhesive formulations for oromucosal drug delivery as this may promote prolonged local therapy and enhanced systemic effect. Saliva plays a vital role in oromucosal drug absorption by dissolving the drug and presenting it to the mucosal surface. However, the rheological, chemical, and interfacial properties of this complex biological fluid may strongly affect the adhesion of bioadhesive formulations. There is a need for well characterized in vitro models to assess the bioadhesive properties of oral dosage forms for administration in the oral cavity. Thus we aimed at developing an advanced ex vivo buccal retention model, with focus on choosing a physiologically relevant irrigation media closely resembling human saliva. Spray dried chitosan microparticles containing metformin hydrochloride as an example of a small hydrophilic drug, were employed as bioadhesive formulations. Chewing-stimulated human whole saliva was collected and characterized for use in retention studies in comparison with four artificial irrigation media; phosphate buffer, Saliva Orthana(®), porcine gastric mucin base media (PGM3), and xanthan gum based media (XG2). Retention of metformin, applied as spray dried microparticles on porcine buccal mucosa, greatly depended on the characteristics of the irrigation media. When rheology of the irrigation media was examined, changes in retention profiles could be interpreted, as irrigation media containing mucin and xanthan gum possessed a higher viscosity than phosphate buffer, which led to longer retention of the drug due to better hydration of the mucosa and the spray dried microparticles. Metformin retention profiles were comparable when human saliva, Saliva Orthana(®), or PGM3 were used as irrigation media. Moreover, PGM3 displayed physico-chemical properties closest to those of human saliva with regard to pH, protein content and surface tension. Saliva Orthana(®) and PGM3 are therefore

  17. 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.

  18. Synthesis, in vitro aerobic and hypoxic cytotoxicity and radiosensitizing activity of novel metronidazole tethered 5-fluorouracil

    PubMed Central

    2013-01-01

    Background and the purpose of the study Several 2, 4-dinitrophenyl and 2,4-dinitrophenylamine tethered 5-FU (5-fluorouracil) compared to their components have shown minimal or no cytotoxicity to HT-29 cell line under aerobic conditions but high cytotoxicity and radiosensitizing effects under hypoxic conditions. In the present study the cytotoxicity and radiation potentiation of three novel analogues of these compounds by replacing 2,4-dinitrophenyl moiety with 2-methyl-5-nitroimidazole, a known radiosensitizer and cytotoxic agent was investigated. Methods Tethered compounds 7–9 were prepared by the reaction of 1-(t-butoxycarbonyl)-5-fluorouracil 6 with metronidazole esters 2–4 followed by removal of the t-butoxycarbonyl protecting group. Cytotoxicity of compounds in HT-29 cells with or without radiation were determined by 3-(4,5-Dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT), propidium iodide (PI)-digitonin and clonogenic assays. Results Tethered compounds 7–9 induced time-and concentration–dependent cytotoxicity under hypoxia but had no significant effect under aerobic conditions. These compounds also showed selective and concentration- dependent radiosensitization effects under hypoxic conditions. Conclusion Tethered compounds 7–9 compared to 5-FU 5 showed minimal cytotoxicities under aerobic and selective radiosensitizing activities under hypoxic conditions. Also effects of these compounds were higher than those of metronidazole 1 which is a known cytotoxin and radiosensitizer under hypoxic conditions. PMID:24359860

  19. Effect of intra-alveolar placement of 0.2% chlorhexidine bioadhesive gel on the incidence of alveolar osteitis following the extraction of mandibular third molars. A double-blind randomized clinical trial

    PubMed Central

    Garcia-Linares, Jordi; Hueto-Madrid, Juan-Antonio; González-Lagunas, Javier; Raspall-Martin, Guillermo; Mareque-Bueno, Javier

    2015-01-01

    Alveolar osteitis (AO) is a common complication after third molar surgery. One of the most studied agents in its prevention is chlorhexidine (CHX), which has proved to be effective. Objectives: The aim of this randomized double-blind clinical trial was to evaluate the efficacy of 0.2% bioadhesive chlorhexidine gel placed intra-alveolar in the prevention of AO after the extraction of mandibular third molars and to analyze the impact of risk factors such as smoking and oral contraceptives in the development of AO. Study Design: The study was a randomized, double-blind, clinical trial performed in the Ambulatory Surgery Unit of Hospital Vall d’Hebron and was approved by the Ethics Committee. A total of 160 patients randomly received 0.2% bioadhesive gel (80 patients) or bioadhesive placebo (80 patients). Results: 0.2% bioadhesive chlorhexidine gel applied in the alveolus after third molar extraction reduced the incidence of dry socket by 22% compared to placebo with differences that were not statistically significant. Smoking and the use of oral contraceptives were not related to higher incidence of dry socket. Female patients and the difficulty of the surgery were associated with a higher incidence of AO with statistically significant differences. 0.2% bioadhesive chlorhexidine gel did not produce any of the side effects related to chlorhexidine rinses. Conclusions: A 22% reduction of the incidence of alveolar osteitis with the application of 0.2% bioadhesive chlorhexidine gel compared to placebo with differences that were not statistically significant was found in this clinical trial. The lack of adverse reactions and complications related to chlorhexidine gel supports its clinical use specially in simple extractions and adds some advantages compared to the rinses in terms of duration of the treatment and reduction of staining and taste disturbance. Key words:Alveolar osteitis, dry socket, chlorhexidine bioadhesive gel, mandibular third molar surgery. PMID

  20. 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 ...

  1. 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

  2. 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.

  3. 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.

  4. A comparison of the in vitro activity of metronidazole, tinidazole, and nimorazole against Gram-negative anaerobic bacilli.

    PubMed Central

    Reynolds, A V; Hamilton-Miller, J M; Brumfitt, W

    1975-01-01

    The in vitro activities of metronidazole, nimorazole, and tinidazole were compared against 69 strains of obligately anaerobic Gram-negative bacilli. Geometric mean MICs were 0-34, 1-05, and 0-28 mug/ml respectively. Thirty-six strains were also tested by the disk method. Correlation between MIC and diameter of the zones of inhibition was poor. PMID:1214009

  5. 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.

  6. 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

  7. The redox-active drug metronidazole and thiol-depleting garlic compounds act synergistically in the protist parasite Spironucleus vortens.

    PubMed

    Williams, C F; Vacca, A R; Dunham, L; Lloyd, D; Coogan, M P; Evans, G; Graz, M; Cable, J

    2016-01-01

    Spironucleus vortens is a protozoan parasite associated with significant mortalities in the freshwater angelfish, Pterophyllum scalare. Control of this parasite is especially problematic due to restrictions on the use of the drug of choice, metronidazole (MTZ), on fish farms. Use of garlic (Allium sativum) is undergoing a renaissance following experimental validations of its antimicrobial efficiency. Ajoene ((E,Z)-4,5,9-trithiadodeca-1,6,11-triene 9-oxide), is a stable transformation product of allicin, the primary biologically active component of garlic. In the current study, an ajoene oil crude extract had a minimum inhibitory concentration (MIC) of 40μg/ml against S. vortens. GC-MS and NMR spectroscopy revealed this ajoene extract contained a mixture of the (E) and (Z)-ajoene isomers along with diallyl disulphide (DADS) and diallyl trisulphide (DATS). The only component of the ajoene crude oil found to substantially inhibit S. vortens growth by optical density monitoring (Bioscreen C Reader) was (Z)-ajoene (MIC 16μg/ml). Ajoene oil acted in synergy with MTZ in vitro, reducing the individual MIC of this drug (4μg/ml) by 16-fold, and that of ajoene oil by 200-fold with a fractional inhibitory concentration (FIC) index of 0.263. This synergistic interaction was confirmed in vivo. S. vortens-infected Pterophyllum scalare angelfish dosed orally with 0.5% (v/w) MTZ combined with 0.05% (v/w) ajoene displayed a significant reduction in faecal trophozoite count, whilst those fed on 0.5% MTZ flakes (half the recommended oral dose) alone did not. This study demonstrates for the first time the synergistic interaction between the synthetic drug MTZ and natural ajoene oil both in vitro and in vivo. Future work should evaluate the potential synergy of ajoene and MTZ against MTZ-resistant bacteria and protists. PMID:26968264

  8. The redox-active drug metronidazole and thiol-depleting garlic compounds act synergistically in the protist parasite Spironucleus vortens.

    PubMed

    Williams, C F; Vacca, A R; Dunham, L; Lloyd, D; Coogan, M P; Evans, G; Graz, M; Cable, J

    2016-01-01

    Spironucleus vortens is a protozoan parasite associated with significant mortalities in the freshwater angelfish, Pterophyllum scalare. Control of this parasite is especially problematic due to restrictions on the use of the drug of choice, metronidazole (MTZ), on fish farms. Use of garlic (Allium sativum) is undergoing a renaissance following experimental validations of its antimicrobial efficiency. Ajoene ((E,Z)-4,5,9-trithiadodeca-1,6,11-triene 9-oxide), is a stable transformation product of allicin, the primary biologically active component of garlic. In the current study, an ajoene oil crude extract had a minimum inhibitory concentration (MIC) of 40μg/ml against S. vortens. GC-MS and NMR spectroscopy revealed this ajoene extract contained a mixture of the (E) and (Z)-ajoene isomers along with diallyl disulphide (DADS) and diallyl trisulphide (DATS). The only component of the ajoene crude oil found to substantially inhibit S. vortens growth by optical density monitoring (Bioscreen C Reader) was (Z)-ajoene (MIC 16μg/ml). Ajoene oil acted in synergy with MTZ in vitro, reducing the individual MIC of this drug (4μg/ml) by 16-fold, and that of ajoene oil by 200-fold with a fractional inhibitory concentration (FIC) index of 0.263. This synergistic interaction was confirmed in vivo. S. vortens-infected Pterophyllum scalare angelfish dosed orally with 0.5% (v/w) MTZ combined with 0.05% (v/w) ajoene displayed a significant reduction in faecal trophozoite count, whilst those fed on 0.5% MTZ flakes (half the recommended oral dose) alone did not. This study demonstrates for the first time the synergistic interaction between the synthetic drug MTZ and natural ajoene oil both in vitro and in vivo. Future work should evaluate the potential synergy of ajoene and MTZ against MTZ-resistant bacteria and protists.

  9. Levofloxacin plus metronidazole administered once daily versus moxifloxacin monotherapy against a mixed infection of Escherichia coli and Bacteroides fragilis in an in vitro pharmacodynamic model.

    PubMed

    Hermsen, Elizabeth D; Hovde, Laurie B; Sprandel, Kelly A; Rodvold, Keith A; Rotschafer, John C

    2005-02-01

    Moxifloxacin has been suggested as an option for monotherapy of intra-abdominal infections. Recent data support the use of a once-daily metronidazole regimen. The purpose of this study was to investigate the activity of levofloxacin (750 mg every 24 h [q24h]) plus metronidazole (1,500 mg q24h) compared with that of moxifloxacin (400 mg q24h) monotherapy in a mixed-infection model. By using an in vitro pharmacodynamic model in duplicate, Escherichia coli and Bacteroides fragilis were exposed to peak concentrations of 8.5 mg of levofloxacin/liter q24h, 32 mg of metronidazole/liter q24h, and 2 mg for moxifloxacin/liter q24h for 24 h. The activities of levofloxacin, metronidazole, moxifloxacin, and levofloxacin plus metronidazole were evaluated against E. coli, B. fragilis, and E. coli plus B. fragilis. The targeted half-lives of levofloxacin, metronidazole, and moxifloxacin were 8, 8, and 12 h, respectively. Time-kill curves were analyzed for time to 3-log killing, slope, and regrowth. Pre- and postexposure MICs were determined. The preexposure levofloxacin, metronidazole, and moxifloxacin MICs for E. coli and B. fragilis were 0.5 and 1, >64 and 0.5, and 1 and 0.25 mg/liter, respectively. Levofloxacin and moxifloxacin achieved a 3-log killing against E. coli and B. fragilis in all experiments, as did metronidazole against B. fragilis. Metronidazole did not decrease the starting inoculum of E. coli. The area under the concentration-time curve/MIC ratios for E. coli and B. fragilis were 171.7 and 85.9, respectively, for levofloxacin and 26 and 103.9, respectively, for moxifloxacin. Levofloxacin plus metronidazole exhibited the fastest rates of killing. The levofloxacin and moxifloxacin MICs for B. fragilis increased 8- to 16-fold after the organism was exposed to moxifloxacin. No other changes in the postexposure MICs were found. Levofloxacin plus metronidazole administered once daily exhibited activity similar to that of moxifloxacin against the mixed E. coli and B

  10. Granular Formation during Apoptosis in Blastocystis sp. Exposed to Metronidazole (MTZ)

    PubMed Central

    Suresh, Kumar; Tan, Tian Chye

    2016-01-01

    The role and function of the granular life cycle stage in Blastocystis sp, remains uncertain despite suggestions being made that the granules are metabolic, reproductive and lipid in nature. This present study aims to understand granular formation by triggering apoptosis in Blastocystis sp. by treating them with metronidazole (MTZ). Blastocystis sp.cultures of 4 sub-types namely 1, 2, 3 and 5 when treated with 0.01 and 0.0001 mg/ml of metronidazole (MTZ) respectively showed many of the parasites to be both viable and apoptotic (VA). Treated subtype 3 isolates exhibited the highest number of granular forms i.e. 88% (p<0.001) (0.0001 mg/ml) and 69% (p<0.01) (0.01 mg/ml) respectively at the 72 h in in vitro culture compared to other subtypes. These VA forms showed distinct granules using acridine orange (AO) and 4’,6-diamino-2-phenylindole (DAPI) staining with a mean per cell ranging from 5 in ST 5 to as high as 16 in ST 3. These forms showed intact mitochondria in both viable apoptotic (VA) and viable non-apoptotic (VNA) cells with a pattern of accumulation of lipid droplets corresponding to viable cells. Granular VA forms looked ultra-structurally different with prominent presence of mitochondria-like organelle (MLO) and a changed mitochondrial trans-membrane potential with thicker membrane and a highly convoluted inner membrane than the less dense non-viable apoptotic (NVA) cells. This suggests that granular formation during apoptosis is a self-regulatory mechanism to produce higher number of viable cells in response to treatment. This study directs the need to search novel chemotherapeutic approaches by incorporating these findings when developing drugs against the emerging Blastocystis sp. infections. PMID:27471855

  11. Granular Formation during Apoptosis in Blastocystis sp. Exposed to Metronidazole (MTZ).

    PubMed

    Dhurga, Devi Balkrishnan; Suresh, Kumar; Tan, Tian Chye

    2016-01-01

    The role and function of the granular life cycle stage in Blastocystis sp, remains uncertain despite suggestions being made that the granules are metabolic, reproductive and lipid in nature. This present study aims to understand granular formation by triggering apoptosis in Blastocystis sp. by treating them with metronidazole (MTZ). Blastocystis sp.cultures of 4 sub-types namely 1, 2, 3 and 5 when treated with 0.01 and 0.0001 mg/ml of metronidazole (MTZ) respectively showed many of the parasites to be both viable and apoptotic (VA). Treated subtype 3 isolates exhibited the highest number of granular forms i.e. 88% (p<0.001) (0.0001 mg/ml) and 69% (p<0.01) (0.01 mg/ml) respectively at the 72 h in in vitro culture compared to other subtypes. These VA forms showed distinct granules using acridine orange (AO) and 4',6-diamino-2-phenylindole (DAPI) staining with a mean per cell ranging from 5 in ST 5 to as high as 16 in ST 3. These forms showed intact mitochondria in both viable apoptotic (VA) and viable non-apoptotic (VNA) cells with a pattern of accumulation of lipid droplets corresponding to viable cells. Granular VA forms looked ultra-structurally different with prominent presence of mitochondria-like organelle (MLO) and a changed mitochondrial trans-membrane potential with thicker membrane and a highly convoluted inner membrane than the less dense non-viable apoptotic (NVA) cells. This suggests that granular formation during apoptosis is a self-regulatory mechanism to produce higher number of viable cells in response to treatment. This study directs the need to search novel chemotherapeutic approaches by incorporating these findings when developing drugs against the emerging Blastocystis sp. infections. PMID:27471855

  12. Development of long-acting bioadhesive vaginal gels of oxybutynin: formulation, in vitro and in vivo evaluations.

    PubMed

    Tuğcu-Demiröz, Fatmanur; Acartürk, Füsun; Erdoğan, Deniz

    2013-11-30

    Overactive bladder (OAB) and vaginal dryness are common problems after menopause. Oxybutynin (OXY) is an antimuscarinic agent that has been available for more than 30 years in the treatment of OAB patients. The aim of the work reported in this paper was to develop long acting mucoadhesive gel formulations of OXY and to investigate their effects on blood levels compared to those of oral OXY immediate release tablets, in rabbits. Mucoadhesive gels were prepared with chitosan, hydroxypropyl methylcellulose (HPMC K100M) and Poloxamer 407 (Pluronic F 127). The physicopharmaceutical properties of gels were evaluated. The gel formulation which was prepared with HPMC K100M, exhibited the highest viscosity, the greatest adhesiveness, cohesiveness and mucoadhesion values. The formulation which was prepared from HPMC K100M showed suitable permeation characteristics across the vaginal mucosa. Comparative bioavailability studies were carried out on rabbits with vaginal HPMC gel, vaginal chitosan gel, vaginal OXY solution and commercially available oral Üropan tablets. It was concluded that the highest AUC and relative bioavailability values were obtained for the bioadhesive vaginal gel formulation prepared with HPMC K100M. Therefore, the mucoadhesive vaginal gels of OXY can be a promising and innovative alternative therapeutic system for the treatment of OAB. It can be safely used in cases of overactive bladder and as well as vaginal dryness after menopause.

  13. 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

  14. Electrochemical synthesis of nickel-iron layered double hydroxide: application as a novel modified electrode in electrocatalytic reduction of metronidazole.

    PubMed

    Nejati, Kamellia; Asadpour-Zeynali, Karim

    2014-02-01

    A new and simple approach based on the electrochemical method was used for preparation of reproducible nanostructure thin film of Ni/Fe-layered double hydroxides (Ni/Fe-LDH) on the glassy carbon electrode (GCE). The electrochemical behavior of the Ni/Fe-LDH deposited on GCE electrode is studied. Study of the scanning electron microscopy shows the formation of a nanostructure thin film on the glassy carbon electrode. Electrochemical experiments show that Ni/Fe-LDH modified glassy carbon electrode exhibits excellent electrocatalytic reduction activity with Metronidazole. The method was successfully applied for the analysis of Metronidazole in tablets. The results were favorably compared to those obtained by the reported BP method.

  15. Application of the bivariate spectrophotometric method for the determination of metronidazole, furazolidone and di-iodohydroxyquinoline in pharmaceutical formulations.

    PubMed

    López-de-Alba, P L; Wróbel, K; López-Martínez, L; Wróbel, K; Yepez-Murrieta, M L; Amador-Hernández, J

    1997-10-01

    The bivariate calibration algorithm was applied to the spectrophotometric determination of metronidazole, furazolidone and di-iodohydroxyquinoline in pharmaceutical dosage forms. The results obtained were compared with the results of derivative spectrophotometry. The statistical evaluation of method bias was carried out, and it was shown that the proposed procedure may be competitive with commonly used first-derivative spectrophotometry. The advantage of the bivariate calibration is its simplicity, and the fact that there is no need to use the derivatization procedures.

  16. 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. PMID:26384884

  17. Treatment of Bacterial Vaginosis: A Multicenter, Double-Blind, Double-Dummy, Randomised Phase III Study Comparing Secnidazole and Metronidazole

    PubMed Central

    Bohbot, Jean-Marc; Vicaut, Eric; Fagnen, Didier; Brauman, Michel

    2010-01-01

    Objective. Multiple-dose metronidazole oral therapy is currently the reference treatment for bacterial vaginosis (BV). This double-blind, double-dummy, noninferiority study compared the efficacy of secnidazole, another nitroimidazole with pharmacokinetics allowing a single dose regimen, to this standard treatment. Methods. A total of 577 patients were randomized to receive metronidazole (500 mg, b.i.d for seven days) or secnidazole (2 g, once). Therapeutic cure at D28 was defined as the resolution of vaginal discharge, positive KOH whiff test, vaginal pH >4.5 and Nugent score >7 on Gram-stained vaginal fluid. Results. According to this primary endpoint, the single-dose secnidazole regimen was shown to be at least as effective as the multiple-dose metronidazole regimen (60.1 % cured women vs 59.5% , 95% confidence interval with a noninferiority margin of 10%: [−0.082; 0.0094]). Safety profiles were comparable in both groups. Conclusion. The secnidazole regimen studied represents an effective, convenient therapeutic alternative that clinicians should consider in routine practice. PMID:20885970

  18. Comparison of in vitro activity of metronidazole and garlic-based product (Tomex®) on Trichomonas vaginalis.

    PubMed

    Ibrahim, Ayman Nabil

    2013-05-01

    Trichomonas vaginalis is a common sexually transmitted parasite in humans. Metronidazole has been the gold standard for treatment of trichomoniasis. The prevalence of metronidazole resistance and its unpleasant adverse effects drew the attention to the investigation of other lines of treatment, as that of herbal medicine. Garlic has been proven to have antibacterial, antiprotozoal, and antihelminthic activity. The current study was carried out to evaluate the efficacy of commercially available garlic (Tomex®) on T. vaginalis in vitro. The effect of different concentrations of garlic (12.5, 25, 50, and 100 μg/ml) was determined on multiplication and motility of trophozoites at different time points (after 24, 48, 72, and 96 h) in comparison to the same concentrations of metronidazole at the same different time points. The results showed that parasite multiplication inhibition was noticed in proportion of concentration of Tomex and incubation time. The minimal lethal concentration of Tomex was 100 μg/ml after 24 h, 50 μg/ml after 48 h, 25 μg/ml after 72 h, and 12.5 μg/ml after 96 h. These results were similar to that of metronidazole as its minimal lethal concentration was 50 μg/ml after 24 and 48 h and 12.5 μg/ml after 72 and 96 h. Garlic had completely inhibited the motility of trophozoites with concentration of 100 μg/ml after 24 h, 50 μg/ml after 48 h, 25 μg/ml after 72 h, and 12.5 μg/ml after 96 h while metronidazole had completely inhibited the motility of trophozoites with concentration of 50 μg/ml after 24 h, 25 μg/ml after 48 h, and 12.5 μg/ml after 72 and 96 h. This suggests that commercially available garlic (Tomex®) may be a promising phytotherapeutic agent for trichomoniasis.

  19. Investigation of PAA/PVDF-NZVI hybrids for metronidazole removal: synthesis, characterization, and reactivity characteristics.

    PubMed

    Yang, Jiacheng; Wang, Xiangyu; Zhu, Minping; Liu, Huiling; Ma, Jun

    2014-01-15

    For the first time, the removal process of metronidazole (MNZ) from aqueous solutions over nano zerovalent iron (NZVI) encapsulated within poly(acrylic acid) (PAA)/poly(vinylidene fluoride) (PVDF) membranes was reported. The resultant composite (PPN) demonstrated high reactivity, excellent stability and reusability over the reaction course. Such excellent performance might be attributed to the presence of the charged carboxyl groups in PVDF membrane support, which could enhance NZVI dispersion and improve its longevity. Results showed that a lower initial concentration and higher reaction temperature facilitated the removal of MNZ by PPN, and that the acidic and neutral conditions generally exhibited more favorable effect on MNZ removal than the alkaline ones. Kinetics of the MNZ removal by PPN was found to follow a two-parameter pseudo-first-order decay model well, and the activation energy of the MNZ degradation by PPN was determined to be 30.49kJ/mol. The presence of chloride ions slightly enhanced the reactivity of PPN with MNZ, whereas sulfate ions inhibited its reactivity. In addition, MNZ degradation pathways by PPN were proposed based on the identified intermediates. This study suggests that PPN composite possessing excellent performance may be a promising functional material to pretreat antibiotic wastewaters.

  20. Development of gastroretentive metronidazole floating raft system for targeting Helicobacter pylori.

    PubMed

    Abou Youssef, Nancy Abdel Hamid; Kassem, Abeer Ahmed; El-Massik, Magda Abd Elsamea; Boraie, Nabila Ahmed

    2015-01-01

    The study demonstrates the feasibility of prolonging gastric residence time and release rate of metronidazole (Mz) by preparing floating raft system (FRS) using ion-sensitive in situ gel forming polymers. FRSs contained 3, 4, 5 and 0.5, 0.75, 1% w/v sodium alginate (Alg) and gellan gum (G), respectively, 0.25% w/v sodium citrate and calcium carbonate (C). Lipids: glyceryl mono stearate (GMS), Precirol(®) and Compritol(®) were incorporated into G-based formulations (G1%C1%). Mz:lipid ratio was 1:1, except for Mz:GMS, ratios of 1:1.5 and 1:2 were also investigated. Buoyancy, gelation capacity and viscosity parameters were evaluated. Drug release and kinetics for selected formulae were examined. The selected lipid containing formula was subjected to an accelerated stability testing. Alg4%C2% FRS exhibited short gelation lag time (3s), long duration (>24h), floating lag time 1m in and duration >24h, and a reliable sustained drug release (MDT 6h). Gellan gum FRSs achieved successful floating gastroretention, but failed to achieve the required gelation capacity. Incorporation of GMS (Mz:GMS 1:1) enhanced the gelation lag time and duration (6s and >24h, respectively), keeping sustained drug release and formulation stability. The improved characteristics of the selected FRS make them excellent candidates for gastric targeting to eradicate Helicobacter pylori. PMID:25843757

  1. Genotoxicity revaluation of three commercial nitroheterocyclic drugs: nifurtimox, benznidazole, and metronidazole.

    PubMed

    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.

  2. 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

  3. Therapeutic Success of Rifaximin for Clostridium difficile Infection Refractory to Metronidazole and Vancomycin

    PubMed Central

    Tannous, George; Neff, Guy; Kemmer, Nyingi

    2010-01-01

    We report the case of a 46-year-old white male with confirmed Clostridium difficile infection for >4 weeks after fluoroquinolone therapy. The patient received two courses of metronidazole 500 mg three times daily (t.i.d.) during which time diarrhea resolved; however, symptoms recurred 14–15 days after treatment termination. He received a 2-week course of vancomycin 125 mg four times daily, with symptoms recurring 10 days after treatment conclusion. The patient then received a pulsed tapering schedule of vancomycin with adjunctive Saccharomyces boulardii. Diarrhea recurred 12 days after treatment completion. He received rifaximin 400 mg t.i.d. while hospitalized for diarrhea-associated complications. Symptoms resolved within 24 h. The patient received a 4-week regimen of rifaximin 400 mg orally t.i.d. after discharge. No further episodes of diarrhea were reported within 6 months after treatment termination. The present case supports the potential benefit of rifaximin for the treatment of recurrent Clostridium difficile infection. PMID:21060709

  4. 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.

  5. Enhanced oral delivery of paclitaxel using acetylcysteine functionalized chitosan-vitamin E succinate nanomicelles based on a mucus bioadhesion and penetration mechanism.

    PubMed

    Lian, He; Zhang, Tianhong; Sun, Jin; Liu, Xiaohong; Ren, Guolian; Kou, Longfa; Zhang, Youxi; Han, Xiaopeng; Ding, Wenya; Ai, Xiaoyu; Wu, Chunnuan; Li, Lin; Wang, Yongjun; Sun, Yinghua; Wang, Siling; He, Zhonggui

    2013-09-01

    In addition to being a physiological protective barrier, the gastrointestinal mucosal membrane is also a primary obstacle that hinders the oral absorption of many therapeutic compounds, especially drugs with a poor permeability. In order to resolve this impasse, we have designed multifunctional nanomicelles based on the acetylcysteine functionalized chitosan-vitamin E succinate copolymer (CS-VES-NAC, CVN), which exhibit marked bioadhesion, possess the ability to penetrate mucus, and enhance the oral absorption of a hydrophobic drug with a poor penetrative profile, paclitaxel. The intestinal absorption (Ka = 0.38 ± 0.04 min(-1), Papp = 0.059 cm · min(-1)) of CVN nanomicelles was greatly improved (4.5-fold) in comparison with paclitaxel solution, and CLSM (confocal laser scanning microscope) pictures also showed not only enhanced adhesion to the intestinal surface but improved accumulation within intestinal villi. The in vivo pharmacokinetics indicated that the AUC0-t (586.37 ng/mL · h) of CVN nanomicelles was markedly enhanced compared with PTX solution. In summary, the novel multifunctional CVN nanomicelles appear to be a promising nanocarrier for insoluble and poorly permeable drugs due to their high bioadhesion and permeation-enhancing capability. PMID:23909663

  6. Influence of tartaric acid on the bioadhesion and mechanical properties of hot-melt extruded hydroxypropyl cellulose films for the human nail.

    PubMed

    Mididoddi, P K; Prodduturi, S; Repka, M A

    2006-10-01

    The objective of this study was to investigate the influence of tartaric acid (TTA) on the bioadhesive, moisture sorption, and mechanical properties of hot-melt-extruded (HME) hydroxypropyl cellulose (HPC) films containing polymer additives. Two Klucel EF and LF batches (HPC, MW: 80000 and 95000, respectively) containing the model antifungal drug ketoconazole (one batch of each MW with and without TTA 4%) were prepared into films by HME using a Killion extruder (Model KLB-100). The bioadhesive properties of the HPC films, with and without TTA, were investigated ex vivo on the human nails. The parameters measured were work of adhesion and peak adhesion force (PAF). A statistically significant increase in both the area under the curve (AUC) and PAF was seen for the HME films containing TTA than those without TTA. Moisture content of hot-melt extruded HPC films was determined using thermogravimetric analysis (TGA). TGA data collected at the two-week interval (25 degrees C/60% RH), measured higher moisture content for the TTA-containing films than those without TTA. Tensile strength and percent elongation were determined utilizing a TA.XT2i Texture Analyzer(R) equipped with a 50-kg load cell, TA-96 grips, and Texture Expert software. TTA functioned as an effective plasticizer, increasing percent elongation and decreasing tensile strength of the HPC films. TTA could potentially be a candidate for transnail applications in film devices prepared by hot-melt extrusion technology.

  7. Enhanced oral delivery of paclitaxel using acetylcysteine functionalized chitosan-vitamin E succinate nanomicelles based on a mucus bioadhesion and penetration mechanism.

    PubMed

    Lian, He; Zhang, Tianhong; Sun, Jin; Liu, Xiaohong; Ren, Guolian; Kou, Longfa; Zhang, Youxi; Han, Xiaopeng; Ding, Wenya; Ai, Xiaoyu; Wu, Chunnuan; Li, Lin; Wang, Yongjun; Sun, Yinghua; Wang, Siling; He, Zhonggui

    2013-09-01

    In addition to being a physiological protective barrier, the gastrointestinal mucosal membrane is also a primary obstacle that hinders the oral absorption of many therapeutic compounds, especially drugs with a poor permeability. In order to resolve this impasse, we have designed multifunctional nanomicelles based on the acetylcysteine functionalized chitosan-vitamin E succinate copolymer (CS-VES-NAC, CVN), which exhibit marked bioadhesion, possess the ability to penetrate mucus, and enhance the oral absorption of a hydrophobic drug with a poor penetrative profile, paclitaxel. The intestinal absorption (Ka = 0.38 ± 0.04 min(-1), Papp = 0.059 cm · min(-1)) of CVN nanomicelles was greatly improved (4.5-fold) in comparison with paclitaxel solution, and CLSM (confocal laser scanning microscope) pictures also showed not only enhanced adhesion to the intestinal surface but improved accumulation within intestinal villi. The in vivo pharmacokinetics indicated that the AUC0-t (586.37 ng/mL · h) of CVN nanomicelles was markedly enhanced compared with PTX solution. In summary, the novel multifunctional CVN nanomicelles appear to be a promising nanocarrier for insoluble and poorly permeable drugs due to their high bioadhesion and permeation-enhancing capability.

  8. 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%. PMID:25594306

  9. 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.

  10. Effect of CPP/ACP on Initial Bioadhesion to Enamel and Dentin In Situ

    PubMed Central

    2014-01-01

    The present in situ study investigated the influence of a preparation containing CPP/ACP (caseinphosphopeptide-amorphous calcium phosphate) (GC Tooth mousse) on initial bacterial colonization of enamel and dentin. Therefore, pellicle formation was performed in situ on bovine enamel and dentin specimens fixed to individual upper jaw splints worn by 8 subjects. After 1 min of pellicle formation GC Tooth mousse was used according to manufacturer's recommendations. Rinses with chlorhexidine served as positive controls. Specimens carried without any rinse served as negative controls. After 8 h overnight exposure of the splints, bacterial colonization was quantified by fluorescence microscopy (DAPI and BacLight live/dead staining). Additionally, the colony forming units (CFU) were determined after desorption. Furthermore, the effects on Streptococcus mutans bacteria were tested in vitro (BacLight). There was no significant impact of CPP/ACP on initial bacterial colonization proved with DAPI and BacLight. Determination of CFU showed statistical significance for CPP/ACP to reduce bacterial adherence on enamel. The in vitro investigation indicated no antimicrobial effects for CPP/ACP on Streptococcus mutans suspension. Under the chosen conditions, CPP/ACP (GC Tooth mousse) had no significant impact on initial biofilm formation on dental hard tissues. The tested preparation cannot be recommended for biofilm management. PMID:25386603

  11. The antitrichomonal efficacy of garlic and metronidazole against Trichomonas gallinae infecting domestic pigeons.

    PubMed

    Seddiek, Sh A; El-Shorbagy, Mohamed M; Khater, Hanem F; Ali, Ali M

    2014-04-01

    Trichomonas gallinae is the causative agent of canker in pigeon. This work was carried out to investigate in the vitro and in vivo efficacy of aqueous water extract of garlic (AGE) on the growth of T. gallinae infecting pigeons compared to those of metronidazole (MTZ). MTZ and AGE were added, at different concentrations, to glucose-serum broth medium containing 1 × 10(4) trophozoites/ml. In the in vivo experiment, 48 squabs were grouped into four groups. The first group (gr. I) was not infected and not treated. Each squab of the other group was infected with 1 × 10(4) trophozoites. The second group (gr. II) was infected and not treated. On day 0, the third group (gr. III) was treated with MTZ (50 mg/kg BW) and the fourth group (gr. IV) was treated with AGE (200 mg/kg BW) for seven successive days in drinking water. In vitro study revealed that the MLC, 24, 48, and 72 h post treatment were 50, 25, and 12.5 μg/ml, respectively, for MTZ and 75, 50, and 50 mg/ml, respectively, for AGE. Garlic (200 mg/kg BW) had the highest antitrichomonal effect and shortened course of treatment of pigeons from 7 days in gr. III to 5 days. Squabs in gr. II suffered from macrocytic hypochromic anemia, whereas squabs in grs. III and IV showed normal blood pictures. Serum total protein, albumin, and globulin were increased, whereas AST, ALT, and the total cholesterol were decreased in grs. III and IV when compared to those of gr. II. Pigeons protected with AGE showed increased body weight and reduced mortality percentage than the other groups. Our results indicated that garlic may be a promising phytotherapeutic agent for protection against trichomoniasis in pigeons.

  12. Impaired Parasite Attachment as Fitness Cost of Metronidazole Resistance in Giardia lamblia▿

    PubMed Central

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

    2011-01-01

    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 (Mzr) G. lamblia has rarely been isolated from patients. To understand why clinical Mzr isolates are rare, we questioned whether Mz resistance entails fitness costs to the parasite. Our studies employed several newly generated and established isogenic Mzr 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 Mzr cell lines could not establish infection, while two Mzr 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 Mzr 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 Mzr isolates of Giardia. However, the data also caution that some forms of Mz resistance do not markedly interfere with in vivo infectivity. PMID:21825286

  13. Investigation of the safety of topical metronidazole from a pharmacokinetic perspective.

    PubMed

    Iida, Junichi; Kudo, Toshiyuki; Shimada, Kento; Yatsuno, Yoshiyuki; Yamagishi, Saori; Hasegawa, Satoshi; Ike, Hideyuki; Sato, Toru; Kagaya, Hajime; Ito, Kiyomi

    2013-01-01

    Metronidazole (MTZ) ointment has been used widely as a hospital preparation against cancerous malodor. Although cancerous tissue with ulcer-like symptoms is likely to have a higher capacity to absorb drugs than normal skin, the extent to which MTZ is absorbed when a topical preparation is applied to cancerous tissue remains unclear. Furthermore, few studies have investigated the drug interactions involving MTZ despite its long use in clinical practice. In the present study, plasma concentration of MTZ was measured in a breast cancer patient using MTZ ointment for cancerous malodor and basic research was also conducted with the objective of investigating the safety of topical MTZ from a pharmacokinetic perspective. 4.75 µg/mL (27.8 µM) of MTZ was detected in the patient's plasma, which was close to the plasma concentration after oral dosage of MTZ. In a metabolic inhibition study using human liver microsomes, cytochrome P450 (CYP) 2C9-mediated hydroxylation of S-warfarin was almost unaffected by MTZ at the corresponding concentrations. In addition, 3-d repeated oral administration of MTZ (200 mg/kg/d) to rats did not show any significant effects on the hepatic mRNA levels of various CYP isozymes and CYP2C protein levels. These results suggest that the reported interaction of oral MTZ and S-warfarin was not due to CYP2C9 inhibition and that drug interactions via inhibition of CYP2C9 is unlikely to occur when MTZ ointment is applied to ulcerous skin. This information should be valuable for assessing the safety of MTZ ointment used for mitigating cancerous malodor. PMID:23302640

  14. Study on The Reproductive Organs and Fertility of The Male Mice following Administration of Metronidazole

    PubMed Central

    Kumari, Mrinalini; Singh, Poonam

    2013-01-01

    Background: Metronidazole (MTZ) is commonly used as an antibacterial and antiprotozoal drug. Various doses of MTZ have been reported to inhibit spermatogenic activity and sperm indices. Materials and Methods: In this experimental study, dose-dependent effects of MTZ on the structural and functional integrity of the testis and accessory reproductive organs have been investigated. Adult male mice of Swiss strain were administered orally with MTZ at the doses of 250 mg/kgBW/day and 500 mg/kgBW/day for 28 consecutive days to study the changes in the testis, epididymis, seminal vesicle, sperm indices and fertility. Reversal effects of the drug were also studied on the same mice, 42 days after cessation of the treatment. Results: Therapeutic dose of MTZ (250 mg/kgBW/day) neither altered the weights of the testis, epididymis and seminal vesicle nor their histoarchitecture and sperm indices. The drug at the high dose (500 mg/kg BW/day) caused significant reductions in the weights of the testis and epididymis. Histoarchitecture of the testis and epididymis at the high dose revealed marked regressive changes while that of seminal vesicle remained unaffected. Significant reductions were noticed in the motility, viability and count of epididymal spermatozoa while the concentrations of epididymal sialic acid and seminal vesicular fructose remained unaltered after the treatment. No significant changes were noticed in the mating ability as well as in the level of serum testosterone in the treated mice. Fertility of the male mice treated with high dose of MTZ declined markedly leading to an increase in pre- and postimplantation loss while a significant decrease was noticed in the number of live blastocysts in females impregnated with such males. MTZinduced changes in the male reproductive organs and fertility were reinstated 42 days after cessation of the treatment. Conclusion: High dose of MTZ induced reversible deleterious effects on the male reproduction and fertility. PMID

  15. 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. PMID:12656265

  16. Synthesis, characterization and application in biomedicine of a novel chondroitin sulfate based hydrogel and bioadhesive

    NASA Astrophysics Data System (ADS)

    Strehin, Iossif

    Clinically, there exists a need for adhesive biomaterials. There is room to improve upon what is currently on the market as it is either too toxic, lacks the required adhesive strength and/or lacks the desired degradation properties. The general goals of this thesis all focused on designing a biomaterial which would improve upon these shortcomings while at the same time allow for modifications to meet the needs for the specific application of interest. To accomplish this task, it was important to choose the appropriate composition and crosslinking chemistry which will allow the most flexibility. Chondroitin sulfate (CS) was chosen as the principle component of the hydrogel because it is a ubiquitous glycosaminoglycan (GAG) found in almost all tissues in the body. Many variants of CS exist with each one possessing unique biological activity allowing for tight control over these properties of the material. To modulate cell migration through the adhesive, polyethylene glycol (PEG) or blood was used as the second constituent. The former made the scaffold act as a cell barrier while the ladder could be used in varying concentrations to modulate cell adhesion and migration into the biomaterial. Also, the CS and blood components are both biodegradable and degradation can be controlled using various methods. While the constituents were chosen to allow flexibility in the biological activity and cell migration into the scaffold, the crosslinking chemistry was chosen to allow control over the mechanical properties as well as to increase tissue adhesion. By functionalizing the carboxyl groups of the GAG with N-hydroxysuccinimide (NHS), the resulting chondroitin sulfate succinimidyl succinate (CS-NHS) molecule could react with primary amines on polymers to form a hydrogel as well as the primary amines on proteins comprising tissue to anchor the hydrogel to the tissue. The material has been characterized and optimized for several applications. The applications described here

  17. 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.

  18. Effectiveness of vaginal administration of Lactobacillus rhamnosus following conventional metronidazole therapy: how to lower the rate of bacterial vaginosis recurrences.

    PubMed

    Marcone, Valentina; Calzolari, Ettore; Bertini, Marco

    2008-07-01

    Eighty-four patients with bacterial vaginosis diagnosed according to Amsel's criteria were randomized to receive either oral metronidazole 500 mg twice a day for seven days, or one vaginal tablet containing freeze-dried Lactobacillus rhamnosus once a week at bedtime for two months starting one week after the last antibiotic administration. Followup was performed at days 30, 90 and 180. Chi-squared analysis showed a significant difference between the two treatment groups at day 90 (P = 0.05). Safe and effective long-term vaginal administration of Lactobacillus rhamnosus appears to be a useful complementary approach in the management of bacterial vaginosis.

  19. 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.

  20. Bioadhesive fluorescent microspheres as visible carriers for local delivery of drugs. II: Uptake of insulin-loaded PCEFB/PLGA microspheres by the gastrointestinal tract.

    PubMed

    Li, Y; Jiang, H L; Jin, J F; Zhu, K J

    2004-01-01

    Uptake of novel inherently fluorescent microspheres composed of a luminescent polyanhydride, poly[p-(carboxyethylformamido)-benzoic anhydride] (PCEFB), and poly(lactide-co-glycolide) (PLGA) (2:1, weight ratio) by the gastrointestinal tract was evaluated by fluorescent microscopy. Oral efficiency of the incorporated insulin also was determined by measuring reduction of plasma glucose levels after feeding diabetic rats with a single dose of the microspheres. We found that PCEFB/PLGA microspheres could adhere to the intestinal epithelium and traverse the absorptive cells. A large number of the spheres were observed in spleen, whereas few were detected in liver within the evaluated period of time. Apparent reduction of the plasma glucose levels was observed over a span of 6 h postfeeding. The unique properties of the delivery system such as biodegradability, bioadhesivity, and inherently luminescent characteristics render it an ideal "visible" tracer for monitoring oral fate of polymeric microspheres. PMID:15736827

  1. Dynamic bio-adhesion of polymer nanoparticles on MDCK epithelial cells and its impact on bio-membranes, endocytosis and paracytosis

    NASA Astrophysics Data System (ADS)

    He, Bing; Yuan, Lan; Dai, Wenbing; Gao, Wei; Zhang, Hua; Wang, Xueqing; Fang, Weigang; Zhang, Qiang

    2016-03-01

    Nowadays, concern about the use of nanotechnology for biomedical application is unprecedentedly increasing. In fact, nanosystems applied for various potential clinical uses always have to cross the primary biological barrier consisting of epithelial cells. However, little is really known currently in terms of the influence of the dynamic bio-adhesion of nanosystems on bio-membranes as well as on endocytosis and transcytosis. This was investigated here using polymer nanoparticles (PNs) and MDCK epithelial cells as the models. Firstly, the adhesion of PNs on cell membranes was found to be time-dependent with a shift of both location and dispersion pattern, from the lateral adhesion of mainly mono-dispersed PNs initially to the apical coverage of the PN aggregate later. Then, it was interesting to observe in this study that the dynamic bio-adhesion of PNs only affected their endocytosis but not their transcytosis. It was important to find that the endocytosis of PNs was not a constant process. A GM1 dependent CDE (caveolae dependent endocytosis) pathway was dominant in the preliminary stage, followed by the co-existence of a CME (clathrin-mediated endocytosis) pathway for the PN aggregate at a later stage, in accordance with the adhesion features of PNs, suggesting the modification of PN adhesion patterns on the endocytosis pathways. Next, the PN adhesion was noticed to affect the structure of cell junctions, via altering the extra- and intra-cellular calcium levels, leading to the enhanced paracellular transport of small molecules, but not favorably enough for the obviously increased passing of PNs themselves. Finally, FRAP and other techniques all demonstrated the obvious impact of PN adhesion on the membrane confirmation, independent of the adhesion location and time, which might lower the threshold for the internalization of PNs, even their aggregates. Generally, these findings confirm that the transport pathway mechanism of PNs through epithelial cells is rather

  2. Effectiveness of trimethoprim-sulfamethoxazole and metronidazole in the treatment of small intestinal bacterial overgrowth in children living in a slum.

    PubMed

    Tahan, Soraia; Melli, Lígia Cristina F L; Mello, Carolina Santos; Rodrigues, Mírian Silva C; Bezerra Filho, Humberto; de Morais, Mauro B

    2013-09-01

    Trimethoprim-sulfamethoxazole and metronidazole were used for 14 days to treat 20 children with small intestine bacterial overgrowth (SIBO). SIBO was diagnosed using the lactulose hydrogen breath test. The breath test was repeated 1 month after treatment, and 19 (95.0%) of 20 children showed no evidence of SIBO (P < 0.001). The area under the individual curves showed that children with SIBO exhibited greater hydrogen production before treatment in both the first hour and between 60 and 180 minutes after the breath test. The treatment did not decrease methane production. In conclusion, trimethoprim-sulfamethoxazole and metronidazole was effective in treating children with SIBO. PMID:23974062

  3. 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. PMID:27108966

  4. Primary resistance to clarithromycin, metronidazole and amoxicillin of Helicobacter pylori isolated from Tunisian patients with peptic ulcers and gastritis: a prospective multicentre study

    PubMed Central

    2010-01-01

    Background The frequency of primary resistance to antibiotics in H. pylori isolates is increasing worldwide. In Tunisia, there are limited data regarding the pattern of H. pylori antibiotic primary resistance. Aim To evaluate the primary resistance of H. pylori to clarithromycin, metronidazole and amoxicillin and to detect the mutations involved in clarithromycin resistance. Materials and methods 273 strains isolated from adults and children were enrolled. The primary resistance to clarithromycin, metronidazole and amoxicillin was evaluated by means of E-test minimal inhibitory concentration (MIC). The real-time PCR using Scorpion primers was performed in all cases to assess clarithromycin primary resistance and point mutations involved. Results No resistance to amoxicillin was detected. For adults, resistance to clarithromycin and metronidazole was found respectively in 14.6% and 56.8%, and respectively in 18.8% and 25% in children. Overall, the rates of global primary resistance to clarithromycin and metronidazole in Tunisia were respectively determined in 15.4% and 51.3%. By the use of Scorpion PCR, the A2143G was the most frequent point mutation observed (88.1%), followed by the A2142G (11.9%); the A2142C was not found and 18 of 42 patients (42.8%) were infected by both the resistant and the susceptible genotype. The association of clarithromycin resistance with gender was not statistically significant, but metronidazole resistant strains were isolated more frequently in females (67.8%) than in males (32.2%) and the difference was significant. As for gastroduodenal diseases, the difference between strains isolated from patients with peptic ulceration and those with non peptic ulceration was not statistically significant. When about the distribution of resistant strains to clarithromycin and metronidazole between the three Tunisian cities (Tunis, Menzel Bourguiba and Mahdia), the difference was not statistically significant. Conclusion Local data regarding the

  5. 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.

  6. 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.

  7. A clinical comparison of cefepime and metronidazole versus gentamicin and clindamycin in the antibiotic management of surgically treated advanced appendicitis.

    PubMed

    Berne, T V; Yellin, A E; Appleman, M D; Heseltine, P N; Gill, M A

    1993-01-01

    Many antibiotics and antibiotic combinations are used for the treatment of peritonitis because of advanced (gangrenous or perforated) appendicitis. An aminoglycoside combined with an antianaerobe antibiotic is one standard treatment, but there is concern about the potential nephrotoxicity of the aminoglycoside and the necessity for monitoring aminoglycoside blood levels. Cefepime, a new broad-spectrum cephalosporin with a prolonged serum half-life, has excellent activity against gram-positive and gram-negative bacteria, including Pseudomonas aeruginosa. Its spectrum of activity is similar to the aminoglycosides, but it has less potential for inducing renal injury. A double-blind, randomized study compared cefepime, 2 grams every 12 hours IVPB plus metronidazole 0.5 grams every eight hours IVPB (C/M) with gentamicin 1.5 milligrams per kilograms of IVPB plus clindamycin 0.9 grams q eight hours IVPB (G/C), administered up to 14 days, in 96 surgically treated patients with gangrenous or perforated appendicitis. Fifty patients had advanced appendicitis (nine gangrenous and 41 perforated) in the C/M group and 46 patients (six gangrenous and 40 perforated) in the G/C group. The mean number of days of postoperative fever (C/M, 4.4 +/- 2.7 versus G/C, 5.0 +/- 2.2), postoperative hospitalization (C/M, 2.0 +/- 1.9 versus G/C, 2.0 +/- 2.1) and antibiotic therapy (C/M, 6.3 +/- 1.9 versus G/C, 6.9 +/- 1.9) was similar in the two treatment groups. There were 11 treatment failures (C/M, three; G/C, eight; p = 0.13), six of which were probably a result of enterococci. No deaths occurred. Our study results show that the efficacy of cefepime plus metronidazole is equivalent to that of clindamycin plus gentamicin.

  8. 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. PMID:24752367

  9. Characterization of the genes rdxA and frxA involved in metronidazole resistance in Helicobacter pylori.

    PubMed

    Marais, Armelle; Bilardi, Claudio; Cantet, Franck; Mendz, George L; Mégraud, Francis

    2003-03-01

    Metronidazole (Mtz) resistance in Helicobacter pylori has been found to be associated with mutations in rdxA, a gene encoding an oxygen-insensitive NADPH nitroreductase, and enhanced by mutations in frxA, a gene encoding a NAD(P)H-flavin oxidoreductase. The roles of these two genes in Mtz resistance in H. pylori were examined in this study. The rdxA and frxA genes were sequenced in nine pairs of strains isolated from biopsies obtained from patients before and after failed eradication treatments which included Mtz and resulted in the appearance of resistant strains. Metronidazole resistance could be explained in seven of these pairs of strains by mutations in rdxA and frxA. However, in one pair of strains, rdxA was identical in the susceptible and resistant strains, and only changes in frxA were observed; and in another pair, neither rdxA nor frxA were different in the susceptible and resistant strains. Sequencing of the upstream region of frxA and of the recA gene in the latter pair of strains did not reveal any mutations. To establish whether mutations in frxA alone could be involved in Mtz resistance, a resistant Escherichia coli strain transformed with the frxA of a Mtz susceptible H. pylori strain was rendered susceptible, and transformation with a mutated H. pylori frxA gene under the same conditions did not change the resistant E. coli phenotype. The results suggested that a Mtz resistance phenotype may arise in H. pylori without mutations in rdxA or frxA, or with mutations only in frxA. PMID:12648728

  10. Mechanically resilient, injectable, and bioadhesive supramolecular gelatin hydrogels crosslinked by weak host-guest interactions assist cell infiltration and in situ tissue regeneration.

    PubMed

    Feng, Qian; Wei, Kongchang; Lin, Sien; Xu, Zhen; Sun, Yuxin; Shi, Peng; Li, Gang; Bian, Liming

    2016-09-01

    Although considered promising materials for assisting organ regeneration, few hydrogels meet the stringent requirements of clinical translation on the preparation, application, mechanical property, bioadhesion, and biocompatibility of the hydrogels. Herein, we describe a facile supramolecular approach for preparing gelatin hydrogels with a wide array of desirable properties. Briefly, we first prepare a supramolecular gelatin macromer via the efficient host-guest complexation between the aromatic residues of gelatin and free diffusing photo-crosslinkable acrylated β-cyclodextrin (β-CD) monomers. The subsequent crosslinking of the macromers produces highly resilient supramolecular gelatin hydrogels that are solely crosslinked by the weak host-guest interactions between the gelatinous aromatic residues and β-cyclodextrin (β-CD). The obtained hydrogels are capable of sustaining excessive compressive and tensile strain, and they are capable of quick self healing after mechanical disruption. These hydrogels can be injected in the gelation state through surgical needles and re-molded to the targeted geometries while protecting the encapsulated cells. Moreover, the weak host-guest crosslinking likely facilitate the infiltration and migration of cells into the hydrogels. The excess β-CDs in the hydrogels enable the hydrogel-tissue adhesion and enhance the loading and sustained delivery of hydrophobic drugs. The cell and animal studies show that such hydrogels support cell recruitment, differentiation, and bone regeneration, making them promising carrier biomaterials of therapeutic cells and drugs via minimally invasive procedures. PMID:27294539

  11. Photo-crosslinkable cyanoacrylate bioadhesive: shrinkage kinetics, dynamic mechanical properties, and biocompatibility of adhesives containing TMPTMA and POSS nanostructures as crosslinking agents.

    PubMed

    Ghasaban, S; Atai, M; Imani, M; Zandi, M; Shokrgozar, M-A

    2011-11-01

    The study investigates the photo-polymerization shrinkage behavior, dynamic mechanical properties, and biocompatibility of cyanoacrylate bioadhesives containing POSS nanostructures and TMPTMA as crosslinking agents. Adhesives containing 2-octyl cyanoacrylate (2-OCA) and different percentages of POSS nanostructures and TMPTMA as crosslinking agents were prepared. The 1-phenyl-1, 2-propanedione (PPD) was incorporated as photo-initiator into the adhesive in 1.5, 3, and 4 wt %. The shrinkage strain of the specimens was measured using bonded-disk technique. Shrinkage strain, shrinkage strain rate, maximum and time at maximum shrinkage strain rate were measured and compared. Mechanical properties of the adhesives were also studied using dynamic mechanical thermal analysis (DMTA). Biocompatibility of the adhesives was examined by MTT method. The results showed that shrinkage strain increased with increasing the initiator concentration up to 3 wt % in POSS-containing and 1.5 wt % in TMPTMA-containing specimens and plateaued out at higher concentrations. By increasing the crosslinking agent, shrinkage strain, and shrinkage strain rate increased and the time at maximum shrinkage strain rate decreased. The study indicates that the incorporation of crosslinking agents into the cyanoacrylate adhesives resulted in improved mechanical properties. Preliminary MTT studies also revealed better biocompatibility profile for the adhesives containing crosslinking agents comparing to the neat specimens.

  12. Hybrid Formulations of Liposomes and Bioadhesive Polymers Improve the Hypotensive Effect of the Melatonin Analogue 5-MCA-NAT in Rabbit Eyes

    PubMed Central

    Palma, Santiago; Allemandi, Daniel; Herrero-Vanrell, Rocío; Molina-Martínez, Irene T.

    2014-01-01

    For the treatment of chronic ocular diseases such as glaucoma, continuous instillations of eye drops are needed. However, frequent administrations of hypotensive topical formulations can produce adverse ocular surface effects due to the active substance or other components of the formulation, such as preservatives or other excipients. Thus the development of unpreserved formulations that are well tolerated after frequent instillations is an important challenge to improve ophthalmic chronic topical therapies. Furthermore, several components can improve the properties of the formulation in terms of efficacy. In order to achieve the mentioned objectives, we have developed formulations of liposomes (150–200 nm) containing components similar to those in the tear film and loaded with the hypotensive melatonin analog 5-methoxycarbonylamino-N-acetyltryptamine (5-MCA-NAT, 100 µM). These formulations were combined with mucoadhesive (sodium hyaluronate or carboxymethylcellulose) or amphiphilic block thermosensitive (poloxamer) polymers to prolong the hypotensive efficacy of the drug. In rabbit eyes, the decrease of intraocular pressure with 5-MCA-NAT-loaded liposomes that were dispersed with 0.2% sodium hyaluronate, 39.1±2.2%, was remarkably higher compared to other liposomes formulated without or with other bioadhesive polymers, and the effect lasted more than 8 hours. According to the results obtained in the present work, these technological strategies could provide an improved modality for delivering therapeutic agents in patients with glaucoma. PMID:25329636

  13. Controlled release effervescent buccal discs of buspirone hydrochloride: in vitro and in vivo evaluation studies.

    PubMed

    Jaipal, A; Pandey, M M; Charde, S Y; Sadhu, N; Srinivas, A; Prasad, R G

    2016-01-01

    In the present study controlled release effervescent buccal discs of buspirone hydrochloride (BS) were designed using HPMC as rate controlling and bioadhesive polymer by direct compression method. Sodium bicarbonate and citric acid were used in varying amounts as effervescence forming agents. Carbon dioxide evolved due to reaction of sodium bicarbonate and citric acid was explored for its potential as buccal permeation enhancer. The designed buccal discs were evaluated for physical characteristics and in vitro drug release studies. Bioadhesive behavior of designed buccal discs was assessed using texture analyzer. In vivo animal studies were performed in rabbits to study bioavailability of BS in the designed buccal discs and to establish permeation enhancement ability of carbon dioxide. It was observed that effervescent buccal discs have faster drug release compared to non-effervescent buccal discs in vitro and effervescent buccal discs demonstrated significant increase in bioavailability of drug when compared to non-effervescent formulation. Hence, effervescent buccal discs can be used as an alternative to improve the drug permeation resulting in better bioavailability. However, the amount of acid and base used for generation of carbon dioxide should be selected with care as this may damage the integrity of bioadhesive dosage form. PMID:24892624

  14. 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

    2015-05-01

    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.

  15. One-week triple therapy with lansoprazole, clarithromycin, and metronidazole to cure Helicobacter pylori infection in peptic ulcer disease in Korea.

    PubMed

    Perng, C L; Kim, J G; El-Zimaity, H M; Osato, M S; Graham, D Y

    1998-03-01

    The efficacy and acceptability of classical bismuth triple therapy may be limited by poor patient compliance and adverse effects. It is widely agreed that improved, simpler, and reliable therapies are needed to cure Helicobacter pylori infection and foster patient compliance. We evaluated the efficacy and side effects of a Bazzoli triple therapy substituting lansoprazole for omeprazole for H. pylori infection in active peptic ulcer in Korea (30 mg of lansoprazole, 250 mg of clarithromycin, and 400 mg of metronidazole, all twice daily). H. pylori status was evaluated by rapid urease test, histology, and culture at entry and four or more weeks after ending antimicrobial therapy. Fifty-eight patients (mean age: 43 years) with gastric (N = 30) or duodenal ulcer (N = 28) and H. pylori infection were studied. H. pylori was cured in 47 (81%, 95% CI = 69-90%). Mild side effects, including vomiting, diarrhea, and itching, were observed in four patients (7%). Compliance averaged 95%. Fifty-five ulcers (95%) were healed. Pretreatment pylorobulbar deformity was observed in 49 patients (85%), and in 43 (88%) the deformity disappeared after treatment. Pretreatment metronidazole and clarithromycin resistance was observed in 87% and 2% of patients, respectively. The cure rate of H. pylori infection was significantly higher in patients >50 years of age than those <50. Treatment with low-dose one-week lansoprazole, clarithromycin, and metronidazole resulted in a relatively low cure rate, but was well tolerated. Studies to define the optimal duration, dose, and dosing interval of this combination therapy in Korea are needed.

  16. Sono-Fenton process for metronidazole degradation in aqueous solution: Effect of acoustic cavitation and peroxydisulfate anion.

    PubMed

    Ammar, Hafedh Belhadj

    2016-11-01

    The present work investigates the application of an improved treatment approach based on the ultrasound irradiation as clean technology driven Fenton in the presence of peroxydisulfate anion (S2O8(2-)) for the removal of metronidazole (MTZ) from aqueous solution. The sono-generation of sulfate radicals (SO4(-)) as a stronger oxidizing agent from S2O8(2-) (redox potential of 2.6V) has improved the degradation of MTZ. However, no studies have focused on the removal of MTZ using peroxydisulfate anion under sono-Fenton process. The MTZ concentration measurement during the processing allowed the evaluation of the kinetics of organic matter decay. The results have shown that the degradation of MTZ dependent on Fe(2+)/H2O2 molar ratio, temperature and S2O8(2-) concentration. The MTZ concentration decay follows pseudo first-order kinetics, within the range studied. Sono-Fenton process using low iron and hydrogen peroxide doses was proved to be an efficient method for the elimination of MTZ with high degradation rates. At optimum conditions, 96% of MTZ removal was achieved at 60°C in the presence of 1mM of S2O8(2-). PMID:27245967

  17. Phenotypic and transcriptional profiling in Entamoeba histolytica reveal costs to fitness and adaptive responses associated with metronidazole resistance

    PubMed Central

    Penuliar, Gil M.; Nakada-Tsukui, Kumiko; Nozaki, Tomoyoshi

    2015-01-01

    Antimicrobial chemotherapy is critical in the fight against infectious diseases caused by Entamoeba histolytica. Among the drugs available for the treatment of amebiasis, metronidazole (MTZ) is considered the drug of choice. Recently, in vitro studies have described MTZ resistance and the potential mechanisms involved. Costs to fitness and adaptive responses associated with resistance, however, have not been investigated. In this study we generated an HM-1 derived strain resistant to 12 μM MTZ (MTZR). We examined its phenotypic and transcriptional profile to determine the consequences and mRNA level changes associated with MTZ resistance. Our results indicated increased cell size and granularity, and decreased rates in cell division, adhesion, phagocytosis, cytopathogenicity, and glucose consumption. Transcriptome analysis revealed 142 differentially expressed genes in MTZR. In contrast to other MTZ resistant parasites, MTZR did not down-regulate pyruvate:ferredoxin oxidoreductase, but showed increased expression of genes for a hypothetical protein (HP1) and several iron-sulfur flavoproteins, and downregulation of genes for leucine-rich proteins. Fisher's exact test showed 24 significantly enriched GO terms in MTZR, and a 3-way comparison of modulated genes in MTZR against those of MTZR cultured without MTZ and HM-1 cultured with MTZ, showed that 88 genes were specific to MTZR. Overall, our findings suggested that MTZ resistance is associated with specific transcriptional changes and decreased parasite virulence. PMID:25999919

  18. 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.

  19. The molecular basis of inactivation of metronidazole-resistant Helicobacter pylori using polyethyleneimine functionalized zinc oxide nanoparticles.

    PubMed

    Chakraborti, Soumyananda; Bhattacharya, Saurabh; Chowdhury, Rukhsana; Chakrabarti, Pinak

    2013-01-01

    In view of the world wide prevalence of Helicobacter pylori infection, its potentially serious consequences, and the increasing emergence of antibiotic resistant H. pylori strains there is an urgent need for the development of alternative strategies to combat the infection. In this study it has been demonstrated that polyethyleneimine (PEI) functionalized zinc oxide (ZnO) nanoparticles (NPs) inhibit the growth of a metronidazole-resistant strain of H. pylori and the molecular basis of the anti-bacterial activity of ZnO-PEI NP has been investigated. The ZnO-PEI NP was synthesized using a wet chemical method with a core size of approximately 3-7 nm. Internalization and distribution of ZnO-PEI NP without agglomeration was observed in H. pylori cytosol by electron microscopy. Several lines of evidence including scanning electron microscopy, propidium iodide uptake and ATP assay indicate severe membrane damage in ZnO-PEI NP treated H. pylori. Intracellular ROS generation increased rapidly following the treatment of H. pylori with ZnO-PEI NP and extensive degradation of 16S and 23S rRNA was observed by quantitative reverse-transcriptase PCR. Finally, considerable synergy between ZnO-PEI NP and antibiotics was observed and it has been demonstrated that the concentration of ZnO-PEI NP (20 µg/ml) that is non-toxic to human cells could be used in combination with sub-inhibitory concentrations of antibiotics for the inhibition of H. pylori growth.

  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. [The real-time FOCSDT detection method and conditions for dissolution test of metronidazole and vitamin B6 tablets].

    PubMed

    Wu, Jun; Yang, Mei; Li, Xin-Xia; Chen, Jian

    2006-09-01

    A method to monitor the dissolution rate of drug on-line fiber optic chemical sensor dissolution test(FOCSDT) was studied. Bifurcated optical fiber was used to connect the light source and detector, and the common end was dipped in the dissolution vessel. The dissolution process could be monitored through computer. The results show that the high, middle and low concentration group's recovery of metronidazole is 100.8%, 99.8% and 100.6%; and RSD is 2.5, 0.8 and 1.1 respectively, The high, middle and low Concentration group's recovery of vitamin B6 is 98.8%, 100.8% and 98.8%; and RSD is 4.1, 4.1 and 2.5 respectively. This process of analysis can test the whole process of drug and get dissolution graph. The study shows that this process analysis can reflect the real dissolution of drug and obtain the total information. PMID:17112065

  2. 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.

  3. In vivo interaction of anti-cancer drugs with misonidazole or metronidazole: methotrexate, 5-fluorouracil and adriamycin.

    PubMed Central

    Tannock, I. F.

    1980-01-01

    I have studied the effects on growth of two tumours in mice and on host toxicity, of combining Misonidazole (MISO) or Metronidazole (METRO) with Methotrexate (MTX)-5-fluorouracil (FU) or Adriamycin (ADR). The nitroimidazoles alone had no effect on the growth of either tumour, but MISO (1 mg/g) led to a small increase in delay to regrowth of the 16/C mammary carcinoma but not the KHT fibrosarcoma, when given after X-irradiation. MTX was active only against the KHT tumour, and growth delay was not increased by the addition of MISO or METRO. FU delayed growth of both tumours, and growth delay was increased slightly by single-dose MISO. ADR was active only against the 16/C tumour, and delay to regrowth was increased by adding MISO. Host toxicity assessed by death and loss of body weight was much greater when MISO or METRO were added to MTX, and a little greater when they were added to FU. ADR plus MISO caused no deaths and no greater loss of body weight than ADR alone. The addition of MISO to treatment with anticancer drugs led to a slightly greater and more prolonged myelosuppression. METRO and MISO increase the anti-tumour effects of some anti-cancer drugs, but may also increase host toxicity. Nitroimidazoles should be used with caution in combination with chemotherapy. PMID:7459220

  4. Sono-Fenton process for metronidazole degradation in aqueous solution: Effect of acoustic cavitation and peroxydisulfate anion.

    PubMed

    Ammar, Hafedh Belhadj

    2016-11-01

    The present work investigates the application of an improved treatment approach based on the ultrasound irradiation as clean technology driven Fenton in the presence of peroxydisulfate anion (S2O8(2-)) for the removal of metronidazole (MTZ) from aqueous solution. The sono-generation of sulfate radicals (SO4(-)) as a stronger oxidizing agent from S2O8(2-) (redox potential of 2.6V) has improved the degradation of MTZ. However, no studies have focused on the removal of MTZ using peroxydisulfate anion under sono-Fenton process. The MTZ concentration measurement during the processing allowed the evaluation of the kinetics of organic matter decay. The results have shown that the degradation of MTZ dependent on Fe(2+)/H2O2 molar ratio, temperature and S2O8(2-) concentration. The MTZ concentration decay follows pseudo first-order kinetics, within the range studied. Sono-Fenton process using low iron and hydrogen peroxide doses was proved to be an efficient method for the elimination of MTZ with high degradation rates. At optimum conditions, 96% of MTZ removal was achieved at 60°C in the presence of 1mM of S2O8(2-).

  5. Response to metronidazole and oxidative stress is mediated through homeostatic regulator HsrA (HP1043) in Helicobacter pylori.

    PubMed

    Olekhnovich, Igor N; Vitko, Serhiy; Valliere, Meaghan; Hoffman, Paul S

    2014-02-01

    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

  6. 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.

  7. The Natural Antimicrobial Subtilosin A Synergizes with Lauramide Arginine Ethyl Ester (LAE), ε-Poly-L-lysine (Polylysine), Clindamycin Phosphate and Metronidazole, Against the Vaginal Pathogen Gardnerella vaginalis.

    PubMed

    Cavera, Veronica L; Volski, Anna; Chikindas, Michael L

    2015-06-01

    Bacterial vaginosis (BV) is a common, recurrent vaginal infection linked to increased chances of preterm delivery, incidence of sexually transmitted infections and fertility problems. BV is caused by a shift of the vaginal ecosystem from predominately Lactobacillus to a multispecies Actinomyces biofilm with the most common representatives identified as Gardnerella vaginalis and Prevotella spp. Current treatments have been associated with increased resistance as well as negative effects on healthy microbiota. The objective of this study was to evaluate the synergistic potential of ten two-antimicrobial combinations against G. vaginalis and four representative lactobacilli. The four tested antimicrobials were lauramide arginine ethyl ester, ε-poly-L-lysine, clindamycin phosphate, metronidazole and the bacteriocin subtilosin A. The use of bacteriocins as either synergist or alternative treatment positions bacteriocins as an excellent alternative to current antibiotics. The microdilution method was used to determine the minimum inhibitory concentration (MIC) of each of the antimicrobials individually, and the checkerboard assay was used to evaluate these MICs in combination. Clindamycin and subtilosin (CS), and metronidazole and subtilosin were synergistic against G. vaginalis in terms of fractional inhibitory concentration index (FICI). All tested combinations were found to have Bliss synergy. The combination of clindamycin and polylysine (CP) was identified as antagonistic against L. acidophilus in terms of both FICI and Bliss synergy. The combination of clindamycin and metronidazole (CM) was antagonistic against L. vaginalis for both FICI and Bliss synergy. The combinations of CP, clindamycin and LAE, CS, and LAE and polylysine were identified as Bliss antagonistic against L. vaginalis but did not indicate FICI antagonism.

  8. 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.

  9. Optimal Treatment for Complicated Intra-abdominal Infections in the Era of Antibiotic Resistance: A Systematic Review and Meta-Analysis of the Efficacy and Safety of Combined Therapy With Metronidazole

    PubMed Central

    Mikamo, Hiroshige; Yuasa, Akira; Wada, Keiko; Crawford, Bruce; Sugimoto, Naomi

    2016-01-01

    Background. Carbapenem-resistant Enterobacteriaceae has increased dramatically in the last decade, resulting in infections that are difficult to treat and associated with high mortality rates. To prevent further antibacterial resistance, it is necessary to use carbapenem selectively. A combination of metronidazole with an antimicrobial agent active against aerobes is an alternative effective treatment for patients with complicated intra-abdominal infections (cIAIs). This study aimed to compare efficacy and safety of metronidazole combination therapies and carbapenem and to provide clinical evidence regarding the optimal treatment of cIAI. Methods. A systematic review and a meta-analysis of randomized clinical trials in the treatment of cIAI were conducted. The systematic review with PubMed, Embase, and the Cochrane Database of Systematic Reviews followed the Cochrane Handbook's recommended methodology, and the meta-analysis used a Mantel-Haenszel random-effects model with RevMan, version 5.3. Primary endpoints were clinical success and bacteriological eradication, and secondary endpoints were all-cause mortality and drug-related adverse events. Results. Eight studies comparing metronidazole combination therapies and carbapenem were included in the meta-analysis. No difference was found between combined therapy with metronidazole and carbapenem regarding clinical success (odds ratio [OR] = 1.31; 95% confidence interval [CI], .75–2.31), bacteriological eradication (OR = 1.27; 95% CI, .84–1.91), all-cause mortality (OR = 0.61; 95% CI, .37–1.00), or drug-related adverse events (OR = 0.58; 95% CI, .18–1.88). Sensitivity analyses found similar results. Conclusions. Combined therapy with metronidazole is as effective and safe as carbapenem in treatment of cIAI. Therefore, combined therapy with metronidazole offers an effective alternative to carbapenem with low risk of drug resistance. PMID:27704002

  10. Robust, flexible, and bioadhesive free-standing films for the co-delivery of antibiotics and growth factors.

    PubMed

    Chen, Dongdong; Wu, Mingda; Chen, Jie; Zhang, Chunqiu; Pan, Tiezheng; Zhang, Bing; Tian, Huayu; Chen, Xuesi; Sun, Junqi

    2014-11-25

    Free-standing polymer films that adhere strongly to tissue and can codeliver multiple therapeutic agents in a controlled manner are useful as medical plasters. In this study, a bilayer polymer film comprising a drug reservoir layer and a supporting layer is fabricated by spin-coating poly(lactic-co-glycolic acid) (PLGA) on top of a layer-by-layer assembled film of poly(β-amino esters) (PAE), alginate sodium (ALG), and recombinant human basic fibroblast growth factor (bFGF). Apart from bFGF, the bilayer film can also load antibiotic drug ceftriaxone sodium (CTX) by a postdiffusion process. The PLGA supporting layer facilitates the direct peeling of the bilayer film from substrate to produce a robust and flexible free-standing film with excellent adhesion onto the human skin and porcine liver. The excellent adhesion of the bilayer film originates from the ALG component in the drug reservoir layer. CTX is quickly released by easily breaking its electrostatic interaction with the drug reservoir layer, whereas the sustained release of bFGF is due to the slow degradation of PAE component in the drug reservoir layer. Wounds can be synergetically treated by fast release of CTX to effectively eradicate invasive bacteria and by sustained release of bFGF to accelerate wound healing. Our results serve as a basis for designing multifunctional free-standing films with combination therapy for biomedical applications. PMID:25353985

  11. Prolonged Hypocalcemic Effect by Pulmonary Delivery of Calcitonin Loaded Poly(Methyl Vinyl Ether Maleic Acid) Bioadhesive Nanoparticles

    PubMed Central

    Varshosaz, J.; Minaiyan, M.; Forghanian, M.

    2014-01-01

    The purpose of the present study was to design a pulmonary controlled release system of salmon calcitonin (sCT). Therefore, poly(methyl vinyl ether maleic acid) [P(MVEMA)] nanoparticles were prepared by ionic cross-linking method using Fe2+ and Zn2+ ions. Physicochemical properties of nanoparticles were studied in vitro. The stability of sCT in the optimized nanoparticles was studied by electrophoretic gel method. Plasma calcium levels until 48 h were determined in rats as pulmonary-free sCT solution or nanoparticles (25 μg·kg−1), iv solution of sCT (5 μg·kg−1), and pulmonary blank nanoparticles. The drug remained stable during fabrication and tests on nanoparticles. The optimized nanoparticles showed proper physicochemical properties. Normalized reduction of plasma calcium levels was at least 2.76 times higher in pulmonary sCT nanoparticles compared to free solution. The duration of hypocalcemic effect of pulmonary sCT nanoparticles was 24 h, while it was just 1 h for the iv solution. There was not any significant difference between normalized blood calcium levels reduction in pulmonary drug solution and iv injection. Pharmacological activity of nanoparticles after pulmonary delivery was 65% of the iv route. Pulmonary delivery of P(MVEMA) nanoparticles of sCT enhanced and prolonged the hypocalcemic effect of the drug significantly. PMID:24701588

  12. 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.

  13. 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

  14. Effects of a Topically Applied Bioadhesive Berry Gel on Loss of Heterozygosity Indices in Premalignant Oral Lesions

    PubMed Central

    Shumway, Brian S.; Kresty, Laura A.; Larsen, Peter E.; Zwick, Jared C.; Lu, Bo; Fields, Henry W.; Mumper, Russell J.; Stoner, Gary D.; Mallery, Susan R.

    2012-01-01

    Purpose The aim of this study was to assess the effects of topical application of a 10% (w/w) freeze-dried black raspberry (FBR) gel on oral intraepithelial neoplasia (IEN) variables that included histologic diagnoses and loss of heterozygosity (LOH) indices. Microsatellite instability and/or LOH at tumor suppressor gene – associated chromosomal loci have been associated with a higher risk for oral IEN progression to oral squamous cell carcinoma. Previously, our laboratories have shown that FBRs are well tolerated and possess potent antioxidant, apoptotic, and differentiation-inducing properties. Experimental Design Each participant with IEN served as their own internal control. Before treatment, all lesions were photographed, and lesional tissue was hemisected to obtain a pretreatment diagnosis and baseline biochemical and molecular variables. Gel dosing (0.5 g applied four times daily for 6 weeks) was initiated 1 week after the initial biopsy. Genomic DNA was isolated from laser-captured basilar and suprabasilar surface epithelial cells followed by PCR amplification using primer sets that targeted known and presumed tumor suppressor gene loci associated with INK4a/ARF, p53, and FHIT. Allelic imbalance was determined by sequence analysis using normal participant tissues to establish microsatellite marker peak patterns and allele sizes. Results Confirming earlier phase I data, none of the 27 participants developed FBR gel – associated toxicities. Furthermore, our results show histologic regression in a subset of patients as well as statistically significant reduction in LOH at tumor suppressor gene – associated loci. Conclusions These preliminary data suggest that further evaluation of berry gels for oral IEN chemoprevention is warranted. PMID:18413833

  15. 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 ...

  16. Metronidazole and clarithromycin resistance in Helicobacter pylori determined by measuring MICs of antimicrobial agents in color indicator egg yolk agar in a miniwell format. The Gastrointestinal Physiology Working Group of Universidad Peruana Cayetano Heredia and the Johns Hopkins University.

    PubMed

    Vasquez, A; Valdez, Y; Gilman, R H; McDonald, J J; Westblom, T U; Berg, D; Mayta, H; Gutierrez, V

    1996-05-01

    Resistance of Helicobacter pylori to metronidazole often causes failure of commonly used combination drug treatment regimens. We determined the MICs of metronidazole and clarithromycin against 18 H. pylori strains from Peru using tetrazolium egg yolk (TEY) agar. The MIC results obtained by agar dilution with petri dishes were compared with the results found through a miniwell format. The results of the two protocols for measuring drug susceptibility differed by no more than 1 dilution in all cases. On TEY agar, bright-red H. pylori colonies were easy to identify against a yellow background. Sixty-one percent (11 of 18) of the strains were resistant to metronidazole (MIC, > or = 4 micrograms/ml) and 50% (9 of 18) were resistant to clarithromycin (MIC, > or = 0.125 micrograms/ml), whereas none (0 of 5) of the strains tested were resistant to tetracycline (MIC, > or = 1 micrograms/ml). Thus, the prevalence of metronidazole and clarithromycin resistance in Peru is higher than that in developed regions of the world. The miniwell plate with TEY agar allows easy H. pylori colony identification, requires about one-third less of the costly medium necessary for petri dish assaying, conserves space, and yields MICs equivalent to those with agar dilution in petri dishes.

  17. Nitroreductase-mediated gonadal dysgenesis for infertility control of genetically modified zebrafish.

    PubMed

    Hu, Shao-Yang; Lin, Pei-Yu; Liao, Chia-Hsuan; Gong, Hong-Yi; Lin, Gen-Hwa; Kawakami, Koichi; Wu, Jen-Leih

    2010-10-01

    Genetically modified (GM) fish with desirable features such as rapid growth, disease resistance, and cold tolerance, among other traits, have been established in aquaculture. However, commercially available GM fish are restricted because of global concerns over the incomplete assessments of food safety and ecological impact. The ecological impact concerns include gene flow and escape of the GM fish, which may cause extinction of wild natural fish stocks. Infertility control is a core technology for overcoming this obstacle. Although polyploidy technology, GnRH-specific antisense RNA, and RNAi against GnRH gene expression have been used to cause infertility in fish, these approaches are not 100% reliable and are not heritable. In the present study, zebrafish was used as a model to establish an inducible platform of infertility control in GM fish. Nitroreductase, which converts metronidazole substrate into cytotoxin, was fused with EGFP and expressed specifically by oocytes in the Tg(ZP:NTR-EGFP) by a zona pellucida promoter. Through consecutive immersion of metronidazole from 28 to 42 days posthatching, oocyte-specific EGFP expression was eliminated, and atrophy of the gonads was detected by anatomical analysis. These findings reveal that oocyte-specific nitroreductase-mediated catalysis of metronidazole blocks oogenesis and leads to an undeveloped oocyte. Furthermore, oocyte cell death via apoptosis was detected by a TUNEL assay. We found that the gonadal dysgenesis induced by metronidazole resulted in activation of the ovarian killer gene bok, which is a proapoptotic gene member of the Bcl-2 family and led to infertility. These results show that oocyte-specific nitroreductase-mediated catalysis of metronidazole can cause reliable infertility in zebrafish and could potentially be used as a model for other aquaculture fish species.

  18. Development of floating chitosan-xanthan beads for oral controlled release of glipizide

    PubMed Central

    Kulkarni, Nilesh; Wakte, Pravin; Naik, Jitendra

    2015-01-01

    Introduction: The aim of the present work was to develop controlled release, floating and mucoadhesive beads of glipizide by using the polyionic complexation technique. Plasma half-life of glipizide being 2–4 h was selected for development of controlled release dosage form. Methods: Formulation batches were designed by employing chitosan as cationic and xanthan gum as anionic polymers. In vitro drug release was evaluated for the period of 24 h in phosphate buffer pH 7.4. Results: Sustained release of drug was observed in all formulation batches with % drug release ranging from 87.50% to 100.67%, no significant effect on the drug release was observed after varying chitosan to xanthan gum ratio. Encapsulation efficiency was found to be in the range of 79.48 ± 1.10–94.48 ± 1.52. In vitro bioadhesion studies showed that beads had satisfactory bioadhesive strength ranging from 67.11% ± 1.73% to 93.12% ± 1.56%. Buoyancy studies revealed that beads possess comparable floating capacity in the gastric fluids. Swelling kinetics was carried in pH 1.2 and 7.4 buffers. Significant difference (P < 0.05) in swelling kinetics was observed. Drug to polymer interaction was analyzed by Fourier transform infrared spectroscopy and differential scanning calorimetry studies. Scanning electron microscopy studies revealed that formed beads were discrete with rough and wrinkled surfaces. Conclusions: In conclusion, beads were successfully formed by employing chitosan and xanthan gum and showed to possess sustained release effect. Beads also showed pH dependent swelling kinetics, this property can also be applied for the drugs which are susceptible to the acidic environment in the stomach, and comparable bioadhesive and floating properties were also observed. PMID:25838991

  19. THE EFFICACY OF THREE MEDICINAL PLANTS: GARLIC, GINGER AND MIRAZID AND A CHEMICAL DRUG METRONIDAZOLE AGAINST CRYPTOSPORIDIUM PARVUM. I-IMMUNOLOGICAL RESPONSE.

    PubMed

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

    2015-12-01

    Cryptosporidisis parvum is a zoonotic protozoan parasite infects intestinal epithelial cells causing a major health problem for man and animals. Experimentally the immunologic mediated elimination of C. parvum requires CD4+ T cells and IFN-gamma. But, the innate immune responses also have a significant protective role in both man and animals. the mucosal immune response to C. parvum in C57BL/6 neonatal and GKO mice shows a concomitant Thl and Th2 cytokine mRNA expression, with a crucial role for IFN-gamma in the resolution of the infection. NK cells and IFN-gamma have been shown to be important components in immunity in T and B cell-deficient mice, but IFN-gamma-dependent resistance is demonstrated in alymphocytic mice. Epithelial cells may play a vital role in immunity as once infected these cells have increased expression of inflammatory chemokines and cytokines and demonstrate anti-infection killing mechanisms. C. parvum immunological response was used to evaluate the efficacy of anti-cryptosporidisis agents of Garlic, Ginger, Mirazid and Metronidazole in experimentally infected mice.

  20. 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.

  1. 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.

  2. A national survey of the molecular epidemiology of Clostridium difficile in Israel: the dissemination of the ribotype 027 strain with reduced susceptibility to vancomycin and metronidazole.

    PubMed

    Adler, Amos; Miller-Roll, Tamar; Bradenstein, Rita; Block, Colin; Mendelson, Bracha; Parizade, Miriam; Paitan, Yossi; Schwartz, David; Peled, Nehama; Carmeli, Yehuda; Schwaber, Mitchell J

    2015-09-01

    Our goals were to study the molecular epidemiology and antimicrobial susceptibilities of C. difficile strains in Israel. Microbiology laboratories serving 6 general hospitals (GH) and 10 long-term care facilities (LTCF) were asked to submit all stool samples in January-February 2014 that tested positive for C. difficile. Toxigenic C. difficile isolates were recovered in 208 out of 217 samples (95.8%), of which 50 (23.6%) were from LTCFs. Ribotype 027 was the most common type overall, identified in 65 samples (31.8%), and was the predominant strain in the 3 GHs with the highest incidence of C. difficile infections. Other common strains were slpA types cr-02 (n = 45) and hr-02 (n = 18). The proportions of vancomycin and metronidazole MIC values >2mg/L were high in ribotype 027 (87.7% and 44.6%, respectively) and slpA-cr-02 strains (88.8% and 17.8%, respectively). This study demonstrates that the ribotype 027 strain has disseminated across Israel and is now the most common strain.

  3. THE EFFICACY OF THREE MEDICINAL PLANTS: GARLIC, GINGER AND MIRAZID AND A CHEMICAL DRUG METRONIDAZOLE AGAINST CRYPTOSPORIDIUM PARVUM. I-IMMUNOLOGICAL RESPONSE.

    PubMed

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

    2015-12-01

    Cryptosporidisis parvum is a zoonotic protozoan parasite infects intestinal epithelial cells causing a major health problem for man and animals. Experimentally the immunologic mediated elimination of C. parvum requires CD4+ T cells and IFN-gamma. But, the innate immune responses also have a significant protective role in both man and animals. the mucosal immune response to C. parvum in C57BL/6 neonatal and GKO mice shows a concomitant Thl and Th2 cytokine mRNA expression, with a crucial role for IFN-gamma in the resolution of the infection. NK cells and IFN-gamma have been shown to be important components in immunity in T and B cell-deficient mice, but IFN-gamma-dependent resistance is demonstrated in alymphocytic mice. Epithelial cells may play a vital role in immunity as once infected these cells have increased expression of inflammatory chemokines and cytokines and demonstrate anti-infection killing mechanisms. C. parvum immunological response was used to evaluate the efficacy of anti-cryptosporidisis agents of Garlic, Ginger, Mirazid and Metronidazole in experimentally infected mice. PMID:26939233

  4. 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

  5. Delivery of granulocyte-macrophage colony-stimulating factor in bioadhesive hydrogel stimulates migration of dendritic cells in models of human papillomavirus-associated (pre)neoplastic epithelial lesions.

    PubMed

    Hubert, Pascale; Evrard, Brigitte; Maillard, Catherine; Franzen-Detrooz, Elizabeth; Delattre, Luc; Foidart, Jean-Michel; Noël, Agnes; Boniver, Jacques; Delvenne, Philippe

    2004-11-01

    Because of the central role of dendritic cells and/or Langerhans cells(DC/LC) in the induction of cellular immune responses, pharmacological agents that modulate the recruitment of these cells might have a clinical interest. The present study was designed to evaluate the capacity of several pharmaceutical formulations to topically deliver granulocyte-macrophage colony-stimulating factor (GM-CSF) on human papillomavirus (HPV)-associated genital (pre)neoplastic lesions. The formulations were evaluated for their bioactivity and for their potential to recruit DC in organotypic cultures of HPV-transformed keratinocytes. We found that a bioadhesive polycarbophil gel (Noveon) at pH 5.5 is able to maintain the bioactivity of GM-CSF at 4 or 37 degrees C for at least 7 days, whereas a decreased activity of GM-CSF was observed when the molecule is included in other polymer gels. GM-CSF incorporated in the polycarbophil gel was also a potent factor in enhancing the colonization of DC into organotypic cultures of HPV-transformed keratinocytes since the infiltration of DC in the in vitro-formed (pre)neoplastic epithelium was very low under basal conditions and dramatically increased in the presence of GM-CSF gel. We next demonstrated that GM-CSF incorporated in polycarbophil gel induces the recruitment of human DC in a human (pre)neoplastic epithelium grafted into NOD/SCID mice. The efficacy of GM-CSF in this formulation was equivalent to that observed with liquid GM-CSF. These results suggest that GM-CSF incorporated in polycarbophil gel could play an important role in the recruitment of DC/LC in mucosal surfaces and be useful as a new immunotherapeutic approach for genital HPV-associated (pre)neoplastic lesions.

  6. Functional Analysis of the RdxA and RdxB Nitroreductases of Campylobacter jejuni Reveals that Mutations in rdxA Confer Metronidazole Resistance▿ †

    PubMed Central

    Ribardo, Deborah A.; Bingham-Ramos, Lacey K.; Hendrixson, David R.

    2010-01-01

    Campylobacter jejuni is a leading cause of gastroenteritis in humans and a commensal bacterium of the intestinal tracts of many wild and agriculturally significant animals. We identified and characterized a locus, which we annotated as rdxAB, encoding two nitroreductases. RdxA was found to be responsible for sensitivity to metronidazole (Mtz), a common therapeutic agent for another epsilonproteobacterium, Helicobacter pylori. Multiple, independently derived mutations in rdxA but not rdxB resulted in resistance to Mtz (Mtzr), suggesting that, unlike the case in H. pylori, Mtzr might not be a polygenic trait. Similarly, Mtzr C. jejuni was isolated after both in vitro and in vivo growth in the absence of selection that contained frameshift, point, insertion, or deletion mutations within rdxA, possibly revealing genetic variability of this trait in C. jejuni due to spontaneous DNA replication errors occurring during normal growth of the bacterium. Similar to previous findings with H. pylori RdxA, biochemical analysis of C. jejuni RdxA showed strong oxidase activity, with reduction of Mtz occurring only under anaerobic conditions. RdxB showed similar characteristics but at levels lower than those for RdxA. Genetic analysis confirmed that rdxA and rdxB are cotranscribed and induced during in vivo growth in the chick intestinal tract, but an absence of these genes did not strongly impair C. jejuni for commensal colonization. Further studies indicate that rdxA is a convenient locus for complementation of mutants in cis. Our work contributes to the growing knowledge of determinants contributing to susceptibility to Mtz (Mtzs) and supports previous observations of the fundamental differences in the activities of nitroreductases from epsilonproteobacteria. PMID:20118248

  7. One week treatment with omeprazole, clarithromycin and tinidazole or lansoprazole, amoxicillin and metronidazole for cure of Helicobacter pylori infection in duodenal ulcer patients.

    PubMed

    Sito, E; Konturek, P C; Bielański, W; Kwiecień, N; Konturek, S J; Baniukiewicz, A; Jedynak, M; Gabryelewicz, A; Hahn, E G

    1996-03-01

    We defined optimal Helicobacter pylori (Hp) treatment as Hp eradication rate about 90%, well-tolerated with few side-effects. Two centers carried out randomized trials including 90 patients (74% men, 26% women, ages ranging from 18 to 65, mean age 42 +/- 8) with active duodenal ulcers (DU). Patients were treated with the combination of Omeprazole (O) 20 mg bd + Clarithromycin (C) 250 mg bd + Tinidazole (T) (500 mg bd) or with Lansoprazole (L) 15 mg bd + Amoxicillin (A) 750 mg bd + Metronidazole (M) 500 mg bd administered for one week. The DU healing rate was evaluated by endoscopy and the Hp status by rapid urease CLO-test and 14C-urea breath test (UBT). The healing rate of the DU in a group treated with the combination of O + C + T was 91% and in group treated with L + A + M was 93%. The eradication of Hp in group O + C + T and L + A + M averaged 91% and 87%, respectively. There was no statistically significant difference in the DU healing rate and the Hp eradication rate between these two groups. Both treatments were accompanied by a marked rise in the basal and postprandial plasma gastrin levels and the rise in the intragastric pH but these alterations returned to the pre-treatment values 4 weeks after the termination of the therapy. Both treatments were well tolerated and the only side effect was the taste disturbance observed in few patents treated with O + C + T. None of patients discontinued the treatment because of the adverse events. We conclude that one week treatment using O + C + T or L + A + M are highly and equally effective in the healing of DU and in the eradication of Hp.

  8. Intra-subtype variation in enteroadhesion accounts for differences in epithelial barrier disruption and is associated with metronidazole resistance in Blastocystis subtype-7.

    PubMed

    Wu, Zhaona; Mirza, Haris; Tan, Kevin Shyong Wei

    2014-05-01

    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.

  9. Shedding of Clostridium difficile PCR ribotype 078 by zoo animals, and report of an unstable metronidazole-resistant isolate from a zebra foal (Equus quagga burchellii).

    PubMed

    Álvarez-Pérez, Sergio; Blanco, José L; Martínez-Nevado, Eva; Peláez, Teresa; Harmanus, Celine; Kuijper, Ed; García, Marta E

    2014-03-14

    Clostridium difficile is an emerging and potentially zoonotic pathogen, but its prevalence in most animal species, including exhibition animals, is currently unknown. In this study we assessed the prevalence of faecal shedding of C. difficile by zoo animals, and determined the ribotype, toxin profile and antimicrobial susceptibility of recovered isolates. A total of 200 samples from 40 animal species (36.5% of which came from plains zebra, Equus quagga burchellii) were analysed. C. difficile was isolated from 7 samples (3.5% of total), which came from the following animal species: chimpanzee (Pan troglodytes troglodytes), dwarf goat (Capra hircus), and Iberian ibex (Capra pyrenaica hispanica), with one positive sample each; and plains zebra, with 4 positive samples from 3 different individuals. Most recovered isolates (4/7, 57.1%) belonged to the epidemic PCR ribotype 078, produced toxins A and B, and had the genes encoding binary toxin (i.e. A(+)B(+)CDT(+) isolates). The remaining three isolates belonged to PCR ribotypes 039 (A(-)B(-)CDT(-)), 042 (A(+)B(+)CDT(-)) and 110 (A(-)B(+)CDT(-)). Regardless of their ribotype, all isolates displayed high-level resistance to the fluoroquinolones ciprofloxacin, enrofloxacin and levofloxacin. Some isolates were also resistant to meropenem and/or ertapenem. A ribotype 078 isolate recovered from a male zebra foal initially showed in vitro resistance to metronidazole (MIC ≥ 256 μg/ml), but lost that trait after subculturing on non-selective media. We conclude that zoo animals belonging to different species can carry ribotype 078 and other toxigenic strains of C. difficile showing resistance to antimicrobial compounds commonly used in veterinary and/or human medicine.

  10. Effect of ethylcellulose and propylene glycol on the controlled-release performance of glyceryl monooleate-mertronidazole periodontal gel.

    PubMed

    Sallam, Al-Sayed; Hamudi, Firas Falih; Khalil, Enam Ayoub

    2015-03-01

    Controlled-release metronidazole, mucoadhesive gel proposed as a drug-delivery system for periodontal application was developed and characterized. The system was based on a mixture of glycerylmonooleate (GMO) and ethylcellulose (EC). The mechanism of release depends: firstly, on the ability of GMO to form a viscous liquid crystalline mesophases and secondly on the solubilized EC to form a hydrophobic network when the mixture comes into contact with water resulting in sustaining the release of the drug. Ethylcellulose dissolved in GMO had a profound influence on the rate of drug release, reduced the initial drug release and prolonged the sustained release of metronidazole. Propylene glycol (PG) was added to increase the solubility of the drug and water was added with PG to control the viscosity. A controlled release formulation containing w/w, 20% metronidazole, 10% PG, 5% water and 65% GMO that contains 7% EC was found to be mucoadhesive, easily injectable at room temperature, and to follow Fickian diffusion release mechanism. When the drug loading was increased the drug release was accelerated, and the mechanism followed anomalous controlled-release mechanism. Stability studies indicated that the formulation should be stored at 4 °C in a dark place.

  11. Assembly of Colloidal Materials Using Bioadhesive Interactions

    NASA Technical Reports Server (NTRS)

    Hammer, Daniel A.; Hiddessen, Amy L.; Tohver, Valeria; Crocker, John C.; Weitz, David A.

    2002-01-01

    We have pursued the use of biological crosslinking molecules of several types to make colloidal materials at relatively low volume fraction of colloidal particles. The objective is to make binary alloys of colloidal particles, made of two different colloidal particles coated with complementary biological lock-and-key binding molecules, which assemble due to the biological specificity. The long-term goal is to use low affinity lock-and-key biological interactions, so that the can anneal to form crystalline states. We have used a variety of different surface chemistries in order to make colloidal materials. Our first system involved using selectin-carbohydrate (sialyl-Lewis) interactions; this chemistry is derived from immune system. This chemical interaction is of relatively low affinity, with timescales for dissociation of several seconds. Furthermore, the adhesion mediated by these molecules can be reversed by the chelation of calcium atoms; thus assembled structures can be disassembled reversibly. Our second system employed avidin-biotin chemistry. This well-studied system is of high affinity, and is generally irreversible on a laboratory time-scale. Thus, we would expect selectin-carbohydrate interactions at high molecular density and avidin-biotin interactions to give kinetically-trapped structures; however, at low densities, we would expect significant differences in the structure and dynamics of the two materials, owing to their very different release rates. We have also begun to use a third chemistry - DNA hybridization. By attaching single stranded DNA oligonucleotide chains to beads, we can drive the assembly of colloidal materials by hybridization of complementary DNA chains. It is well known that DNA adenosine-thymine (A-T) and guanine-cytosine (G-C) bases hybridize pairwise with a Gibbs free energy change of 1.7 kcal/mol per base; thus, the energy of the assembly can be modulated by altering the number of complementary bases in the DNA chains. Using these different crosslinking molecules, we have assembled colloidal materials from different-sized colloidal particles, A and B. In the first sets of experiment, we used high densities of adhesion molecules, and 0.96 micron (A) and 5.5 micron (B) diameter particles. The high density of adhesion molecules means that the structures are kinetically trapped in nonequilibrium configurations. The structure of the suspension can be varied by changing the number ratio of the two types of colloidal particles, NA and NB, where A is the smaller particle. With carbohydrate-selectin or avidin-biotin interactions, large NA/NB leads to the formation of colloidal micelles, with the large center B particle surrounded by many smaller A particles. As the ratio NA/NB decreases, the structures become more extended, approaching the formation of macro-Rouse polymers - extended linear chains where A beads are connected with intervening small B linkers.

  12. Preparation, characterization and optimization of glipizide controlled release nanoparticles

    PubMed Central

    Emami, J.; Boushehri, M.S. Shetab; Varshosaz, J.

    2014-01-01

    The purpose of the present study was to develop glipizide controlled release nanoparticles using alginate and chitosan thorough ionotropic controlled gelation method. Glipizide is a frequently prescribed second generation sulfonylurea which lowers the blood glucose in type-two diabetics. Quick absorption of the drug from the gastrointestinal tract along with short half- life of elimination makes it a good candidate for controlled release formulations. Alginate-chitosan nanoparticles (ACNP) are convenient controlled delivery systems for glipizide, due to both the release limiting properties of the system, and the bioadhesive nature of the polymers. In the present study, glipizide loaded alginate-chitosan nanoparticles (GlACNP) were prepared, and the particle characteristics including particle size (PS), zeta potential (ZP), entrapment efficiency (EE%), loading percent (LP), and mean release time (MRT), as well as the morphology of the nanoparticles, the drug-excipient compatibility, and the release kinetics along with the drug diffusion mechanism were evaluated. The results suggested that ionotropic controlled gelation method offers the possibility of preparing the nanoparticles in mild conditions in an aqueous environment, and can lead to the preparation of particles with favorable size, controlled release characteristics, and high entrapment efficiency, serving as a convenient delivery system for glipizide. The particle and release characteristics can be efficiently optimized using the Box-Behnken design. Based on the findings of the present study, it is expected that this novel formulation be a superior therapeutic alternative to the currently available glipizide delivery systems. PMID:25657802

  13. 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

    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

  14. 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

  15. Inner reorganization limiting electron transfer controlled hydrogen bonding: intra- vs. intermolecular effects.

    PubMed

    Martínez-González, Eduardo; Frontana, Carlos

    2014-05-01

    In this work, experimental evidence of the influence of the electron transfer kinetics during electron transfer controlled hydrogen bonding between anion radicals of metronidazole and ornidazole, derivatives of 5-nitro-imidazole, and 1,3-diethylurea as the hydrogen bond donor, is presented. Analysis of the variations of voltammetric EpIcvs. log KB[DH], where KB is the binding constant, allowed us to determine the values of the binding constant and also the electron transfer rate k, confirmed by experiments obtained at different scan rates. Electronic structure calculations at the BHandHLYP/6-311++G(2d,2p) level for metronidazole, including the solvent effect by the Cramer/Truhlar model, suggested that the minimum energy conformer is stabilized by intramolecular hydrogen bonding. In this structure, the inner reorganization energy, λi,j, contributes significantly (0.5 eV) to the total reorganization energy of electron transfer, thus leading to a diminishment of the experimental k. PMID:24653999

  16. Intrinsic Surface-Drying Properties of Bio-adhesive Proteins

    PubMed Central

    Akdogan, Yasar; Wei, Wei; Huang, Kuo-Ying; Kageyama, Yoshiyuki; Danner, Eric W.; Miller, Dusty R.; Martinez Rodriguez, Nadine R.; Herbert Waite, J.

    2014-01-01

    Sessile marine mussels must “dry” underwater surfaces before adhering to them. Synthetic adhesives have yet to overcome this fundamental challenge. Previous studies of bio-inspired adhesion have largely been performed under applied compressive forces but these are poor predictors of an adhesive’s ability to spontaneously penetrate surface hydration layers. In a force-free approach to measuring molecular-level interaction via the surface water diffusivity, different mussel foot proteins were found to have differential abilities to evict hydration layers from the surfaces—a necessary step for adsorption and adhesion. It was anticipated that Dopa would mediate dehydration given its efficacy forbio-inspired wet adhesion. Instead, hydrophobic side-chains are found to be a critical component in bringing about protein-surface intimacy. This is the first direct measurement of interfacial water dynamics during force-free adsorptive interactions at solid surfaces, and offers guidance for engineering wet adhesives and coatings. PMID:25168789

  17. Silane surface modification for improved bioadhesion of esophageal stents

    NASA Astrophysics Data System (ADS)

    Karakoy, Mert; Gultepe, Evin; Pandey, Shivendra; Khashab, Mouen A.; Gracias, David H.

    2014-08-01

    Stent migration occurs in 10-40% of patients who undergo placement of esophageal stents, with higher migration rates seen in those treated for benign esophageal disorders. This remains a major drawback of esophageal stent therapy. In this paper, we propose a new surface modification method to increase the adhesion between self-expandable metallic stents (SEMS) and tissue while preserving their removability. Taking advantage of the well-known affinity between epoxide and amine terminated silane coupling agents with amine and carboxyl groups that are abundant in proteins and related molecules in the human body; we modified the surfaces of silicone coated esophageal SEMS with these adhesive self-assembled monolayers (SAMs). We utilized vapor phase silanization to modify the surfaces of different substrates including PDMS strips and SEMS, and measured the force required to slide these substrates on a tissue piece. Our results suggest that surface modification of esophageal SEMS via covalent attachment of protein-binding coupling agents improves adhesion to tissue and could offer a solution to reduce SEMS migration while preserving their removability.

  18. In vitro, in vivo and pharmacokinetic assessment of amikacin sulphate laden polymeric nanoparticles meant for controlled ocular drug delivery

    NASA Astrophysics Data System (ADS)

    Sharma, Upendra Kumar; Verma, Amita; Prajapati, Sunil Kuamr; Pandey, Himanshu; Pandey, Avinash C.

    2015-02-01

    The rationale of current exploration was to formulate positively charged amikacin-loaded polymeric nanoparticles providing a controlled release attribute. Amikacin sulphate-loaded nanoparticles were prepared by w/o/w emulsification solvent evaporation approach succeeded by high-pressure homogenization. Two bioadhesive positively charged polymers, Eudragit® RS 100 and Eudragit® RL 100, were used in the blend, with variable ratios of drug and polymer. The formulations were assessed in terms of particle size and zeta potential. Thermal gravimetric analysis was brought out on the samples of drug, polymer and drug polymer complex. Drug loading and release attributes of the nanoparticles were scrutinized and antimicrobial activity in contrast to Staphylococcus aureus was appraised. Ocular irritation test, in vivo ocular retention study, in vivo release profile (permeation study) and in vivo antibacterial activity of polymeric nanosuspensions were executed. No rupture consequence but a lengthened drug release was contemplated from all formulations. Amikacin sulphate release from the polymeric nanoparticles reflected a better fit with Korsmeyer-Peppas model. In the course of the antibacterial activity of nanoparticles against S. aureus, formulation AE1 displays the most prominent inhibitory effect as compared with marketed formulation of amikacin sulphate.

  19. Lycopene an adjunctive therapy for Helicobacter pylori eradication: a quasi-control trial.

    PubMed

    Shidfar, Farzad; Agah, Shahram; Ekhlasi, Golnaz; Salehpour, Amin; Ghourchian, Shadi

    2012-01-01

    Although some herbal remedies in association with vitamin therapy have been investigated in eradicating HP, no research has been done to investigate the effects of lycopene it. Our aim was to understand if lycopene could be effective in eradication of HP. In this parallel group quasi-control trial, a total of 54 patients whose diagnosis of HP had been confirmed by rapid urease test (RUT) were enrolled. Group 1 received the standard 4-drug therapy to eradicate HP (Metronidazole 500 mg/BD, Amoxicillin 1g/BD, Omeprazole 20mg/BD, and Bismuth 240 mg/BD) and group 2 received the same regimen in association with Lycopene (30 mg/daily). One month after the initiation of the treatment, the patients were evaluated for HP eradication by RUT. Although eradication rate was higher in the second group, bivariate analysis showed no significant statistical difference between the two groups. In contrast with other nutrients, it seems that Lycopene does not have any significant effects on eradicating HP in comparison with the standard antibiotic therapy. The prevalence of HP is in association with socioeconomic situation, so the patients in different studies should be paid more attention about their own life style. We recommend that more studies can be designed by considering control group and placebo administration. PMID:22850072

  20. Transient cefuroxime/metronidazole treatment induced factor V antibodies.

    PubMed

    Van den Berg, Sjoerd Adrianus Antonius; Verwer, Patricia E; Idema, René N; Van Guldener, Coen

    2014-01-01

    A 29-year-old patient presented with an appendicular infiltrate, initially treated with intravenous antibiotics, but later requiring percutaneous drainage. Both prothrombin time (PT) and activated partial thromboplastin time (aPTT) were prolonged on 3 days of antibiotic treatment and unresponsive to vitamin K or prothrombin complex concentrate. Laboratory investigation ultimately showed reduced factor V activity and factor V antibodies. In contrast to previously described cases of factor V antibodies, PT and aPTT were only mildly prolonged and residual factor V activity was still >20%. Draining of the abscess did not induce significant bleeding. Afterwards, no haemostatic medication was required. The patient was discharged from the hospital without complications. One week after cessation of the antibiotic treatment, PT and aPTT were within normal range again, with a factor V activity level of 36%. In conclusion, we present a patient with transient factor V antibodies, induced by antibiotics, without clinical bleeding tendency.

  1. Explanations for high rates of eradication with triple therapy using metronidazole in patients harboring metronidazole-resistant Helicobacter pylori strains.

    PubMed Central

    van Zwet, A A; Thijs, J C; de Graaf, B

    1995-01-01

    In 4 of 17 Helicobacter pylori strains obtained from antral biopsy samples, the registered primary resistance (MIC, > 32 microgram/ml) appeared to be nonstable after prolonged microaerophilic incubation. In all resistant strains tested, susceptibility could be obtained when culture under normal microaerophilic conditions was preceded by a period of anaerobic incubation. Both of these findings may explain the observed discrepancy between the results of in vitro susceptibility tests and the eradication obtained in vivo. PMID:7695317

  2. Controllable attenuators

    NASA Astrophysics Data System (ADS)

    Krylov, G. M.; Khoniak, E. I.; Tynynyka, A. N.; Iliushenko, V. N.; Sikolenko, S. F.

    Methods for the synthesis of controllable attenuators and their implementations are examined. In particular, attention is given to the general properties of controllable attenuators, control elements, types of controllable attenuators and methods of their analysis, and synthesis of the control characteristic of attenuators. The discussion also covers the efficiency of attenuator control, the use of transmission line segments in wide-band controllable attenuators, and attenuators with a discretely controlled transmission coefficient.

  3. Dream controller

    DOEpatents

    Cheng, George Shu-Xing; Mulkey, Steven L; Wang, Qiang; Chow, Andrew J

    2013-11-26

    A method and apparatus for intelligently controlling continuous process variables. A Dream Controller comprises an Intelligent Engine mechanism and a number of Model-Free Adaptive (MFA) controllers, each of which is suitable to control a process with specific behaviors. The Intelligent Engine can automatically select the appropriate MFA controller and its parameters so that the Dream Controller can be easily used by people with limited control experience and those who do not have the time to commission, tune, and maintain automatic controllers.

  4. DEVICE CONTROLLER, CAMERA CONTROL

    1998-07-20

    This is a C++ application that is the server for the cameral control system. Devserv drives serial devices, such as cameras and videoswitchers used in a videoconference, upon request from a client such as the camxfgbfbx ccint program. cc Deverv listens on UPD ports for clients to make network contractions. After a client connects and sends a request to control a device (such as to pan,tilt, or zooma camera or do picture-in-picture with a videoswitcher),more » devserv formats the request into an RS232 message appropriate for the device and sends this message over the serial port to which the device is connected. Devserv then reads the reply from the device from the serial port to which the device is connected. Devserv then reads the reply from the device from the serial port and then formats and sends via multicast a status message. In addition, devserv periodically multicasts status or description messages so that all clients connected to the multicast channel know what devices are supported and their ranges of motion and the current position. The software design employs a class hierarchy such that an abstract base class for devices can be subclassed into classes for various device categories(e.g. sonyevid30, cononvco4, panasonicwjmx50, etc.). which are further subclassed into classes for various device categories. The devices currently supported are the Sony evi-D30, Canon, VCC1, Canon VCC3, and Canon VCC4 cameras and the Panasonic WJ-MX50 videoswitcher. However, developers can extend the class hierarchy to support other devices.« less

  5. DEVICE CONTROLLER, CAMERA CONTROL

    SciTech Connect

    Perry, Marcia

    1998-07-20

    This is a C++ application that is the server for the cameral control system. Devserv drives serial devices, such as cameras and videoswitchers used in a videoconference, upon request from a client such as the camxfgbfbx ccint program. cc Deverv listens on UPD ports for clients to make network contractions. After a client connects and sends a request to control a device (such as to pan,tilt, or zooma camera or do picture-in-picture with a videoswitcher), devserv formats the request into an RS232 message appropriate for the device and sends this message over the serial port to which the device is connected. Devserv then reads the reply from the device from the serial port to which the device is connected. Devserv then reads the reply from the device from the serial port and then formats and sends via multicast a status message. In addition, devserv periodically multicasts status or description messages so that all clients connected to the multicast channel know what devices are supported and their ranges of motion and the current position. The software design employs a class hierarchy such that an abstract base class for devices can be subclassed into classes for various device categories(e.g. sonyevid30, cononvco4, panasonicwjmx50, etc.). which are further subclassed into classes for various device categories. The devices currently supported are the Sony evi-D30, Canon, VCC1, Canon VCC3, and Canon VCC4 cameras and the Panasonic WJ-MX50 videoswitcher. However, developers can extend the class hierarchy to support other devices.

  6. Rodent Control

    ERIC Educational Resources Information Center

    Indian Journal of Adult Education, 1975

    1975-01-01

    Strategies for rodent control in crop fields, threshing yards, and rural residential areas are presented together with an operational plan for implementing a program for rodent control at the national level. Training personnel in rodent control procedures and procedures for educating the public in the necessity for control are covered. (EC)

  7. Fibrous guided tissue regeneration membrane loaded with anti-inflammatory agent prepared by coaxial electrospinning for the purpose of controlled release

    NASA Astrophysics Data System (ADS)

    He, Min; Xue, Jiajia; Geng, Huan; Gu, Hao; Chen, Dafu; Shi, Rui; Zhang, Liqun

    2015-04-01

    Here, with the aim of inhibiting inflammation during guided tissue regeneration membrane (GTRM) implant surgery, coaxial electrospinning was used to fabricate drug-loaded core/sheath nanofiber GTRMs capable of controlled drug release. Various amounts of the anti-inflammatory agent metronidazole (MNA) were encapsulated into the core/sheath nanofibers (where PCL was the core, gelatin the sheath, and the gelatin shell was crosslinked with genipin) in order to establish the minimal drug content necessary to achieve the appropriate anti-inflammatory effect. By using TEM and SEM, the core/sheath structure was confirmed. In vitro drug disolution results showed that the core/sheath nanofibers exhibited sustained release profiles that were superior to those nanofibers produced by blending electrospinning. Additionally, the membrane significantly inhibited the colonization of anaerobic bacteria. Furthermore, with gelatin as a shell, the core/shell nanofiber membranes showed improved hydrophilicity, which resulted in better cell adhesion and proliferation without cytotoxicity. Therefore, in this study, a simple and effective coaxial electrospinning approach was demonstrated for the fabrication of anti-inflammatory GTRMs capable of providing controlled drug release.

  8. Weight Control

    MedlinePlus

    ... obese. Achieving a healthy weight can help you control your cholesterol, blood pressure and blood sugar. It ... use more calories than you eat. A weight-control strategy might include Choosing low-fat, low-calorie ...

  9. [Vector control and malaria control].

    PubMed

    Carnevale, P; Mouchet, J

    1990-01-01

    Vector control is an integral part of malaria control. Limiting parasite transmission vector control must be considered as one of the main preventive measure. Indeed it prevents transmission of Plasmodium from man to vector and from vector to man. But vector control must be adapted to local situation to be efficient and feasible. Targets of vector control can be larval and/or adults stages. In both cases 3 main methods are currently available: physical (source reduction), chemical (insecticides) and biological tolls. Antilarval control is useful only in some particular circumstances (unstable malaria, island, oasis...) Antiadult control is mainly based upon house-spraying while pyrethroid treated bed nets is advocated regarding efficiency, simple technique and cheap price. Vector control measures could seem restricted but can be very efficient if political will is added to a right choice of adapted measures, a good training of involved personal and a large information of the population concerned with vector control.

  10. Contamination Control.

    PubMed

    Akers, Michael J

    2015-01-01

    There are serious consequences if contamination control is not enforced and contaminated products/preparations are released to the market. The greatest risk of microbial contamination is exposure of sterile (also termed "critical") sites to potential sources of contamination. Contamination control basically involves at least fourteen entities to control or that help to determine the extent (quality) of control. Some of these entities are covered in this article; others will be covered in subsequent articles by the author.

  11. Controlling Fertility.

    ERIC Educational Resources Information Center

    Donnay, France

    1991-01-01

    Recent developments in fertility control are presented in relation to the global demographic situation. Discussion focuses on changes in scientific knowledge and concepts that have shifted the focus from birth control to planned parenthood to the notion of controlled fertility. The place of family planning programs, including their socioeconomic…

  12. Restructurable Controls

    NASA Technical Reports Server (NTRS)

    Montoya, R. J. (Compiler); Howell, W. E. (Compiler); Bundick, W. T. (Compiler); Ostroff, A. J. (Compiler); Hueschen, R. M. (Compiler); Belcastro, C. M. (Compiler)

    1983-01-01

    Restructurable control system theory, robust reconfiguration for high reliability and survivability for advanced aircraft, restructurable controls problem definition and research, experimentation, system identification methods applied to aircraft, a self-repairing digital flight control system, and state-of-the-art theory application are addressed.

  13. Birth Control

    MedlinePlus

    ... to have sex makes sense Talking to your parents about sex Deciding about sex Birth control Types of birth control Could I get pregnant ... not planned. Some young people are afraid their parents will find out they’re having sex. If you get birth control from a doctor, ask about keeping the information ...

  14. Controlled drugs.

    PubMed

    2016-05-18

    Essential facts Controlled drugs are defined and governed by the Misuse of Drugs Act 1971 and associated regulations. Examples of controlled drugs include morphine, pethidine and methadone. Since 2012, appropriately qualified nurses and midwives can prescribe controlled drugs for medical conditions within their competence. There are some exceptions when treating addiction. PMID:27191427

  15. Formulation and evaluation of bilayer tablet for bimodal release of venlafaxine hydrochloride.

    PubMed

    Momin, Munira M; Kane, Snehal; Abhang, Pooja

    2015-01-01

    The aim of the present research was to develop a bilayer tablet of venlafaxine hydrochloride for bimodal drug release. In the present investigation authors have tried to explore fenugreek mucilage (FNM) for bioadhesive sustained release layer. The attempt has been made to combine FNM with well studied bioadhesive polymers like hydroxy propyl methyl cellulose (HPMC), Carbopol, and Xanthan Gum. The formulations were evaluated for swelling Index, ex vivo bioadhesion, water uptake studies, in vitro drug release and dissolution kinetics was studied. Substantial bioadhesion force (2.4 ± 0.023 g) and tablet adhesion retention time (24 ± 2 h) was observed with FNM and HPMC combination at 80:20 ratio. The dissolution kinetics followed the Higuchi model (R (2) = 0.9913) via a non-Fickian diffusion controlled release mechanism after the initial burst. The 3(2) full factorial design was employed in the present study. The type of polymers used in combination with FNM (X1) and percent polymer replaced with FNM (X2) were taken as independent formulations variables. The selected responses, bioadhesion force (0.11-0.25 ± 0.023 g), amount of drug released in 10 h, Y10 (78.20-95.78 ± 1.24%) and bioadhesive strength, (19-24 ± 2 h) presented good correlation with the selected independent variables. Statistical analysis (ANOVA) of the optimized bilayer formulations showed no significant difference in the cumulative amount of drug release after 15 min, but significant difference (p < 0.05) in the amount of drug released after 1 hr till 12 h from optimized formulations was observed. The natural mucilage like FNM could be successfully incorporated into tablet with only 20% replacement with HPMC and it showed good bioadhesiveness and sustained drug release. PMID:26217229

  16. Formulation and evaluation of bilayer tablet for bimodal release of venlafaxine hydrochloride

    PubMed Central

    Momin, Munira M.; Kane, Snehal; Abhang, Pooja

    2015-01-01

    The aim of the present research was to develop a bilayer tablet of venlafaxine hydrochloride for bimodal drug release. In the present investigation authors have tried to explore fenugreek mucilage (FNM) for bioadhesive sustained release layer. The attempt has been made to combine FNM with well studied bioadhesive polymers like hydroxy propyl methyl cellulose (HPMC), Carbopol, and Xanthan Gum. The formulations were evaluated for swelling Index, ex vivo bioadhesion, water uptake studies, in vitro drug release and dissolution kinetics was studied. Substantial bioadhesion force (2.4 ± 0.023 g) and tablet adhesion retention time (24 ± 2 h) was observed with FNM and HPMC combination at 80:20 ratio. The dissolution kinetics followed the Higuchi model (R2 = 0.9913) via a non-Fickian diffusion controlled release mechanism after the initial burst. The 32 full factorial design was employed in the present study. The type of polymers used in combination with FNM (X1) and percent polymer replaced with FNM (X2) were taken as independent formulations variables. The selected responses, bioadhesion force (0.11–0.25 ± 0.023 g), amount of drug released in 10 h, Y10 (78.20–95.78 ± 1.24%) and bioadhesive strength, (19–24 ± 2 h) presented good correlation with the selected independent variables. Statistical analysis (ANOVA) of the optimized bilayer formulations showed no significant difference in the cumulative amount of drug release after 15 min, but significant difference (p < 0.05) in the amount of drug released after 1 hr till 12 h from optimized formulations was observed. The natural mucilage like FNM could be successfully incorporated into tablet with only 20% replacement with HPMC and it showed good bioadhesiveness and sustained drug release. PMID:26217229

  17. Initial bioadhesion on surfaces in the oral cavity investigated by scanning force microscopy

    NASA Astrophysics Data System (ADS)

    Schwender, N.; Huber, K.; Marrawi, F. Al; Hannig, M.; Ziegler, Ch.

    2005-09-01

    Scanning force microscopy (SFM) was used to measure the adhesion forces between BSA, a saliva protein, and two dental surfaces, natural enamel and a filling material (Dyract AP™). Measurements were taken in phosphate buffered aqueous solutions (PBS). Forces were resolved down to the piconewton regime. The dependency of the adhesion force on the interaction time, pH-value and substrate surface was monitored. In a further step, surface samples were fixed on an enamel brace and carried for a defined time in the oral cavity. The formed biofilm, called pellicle, shows a different morphology on the different substrates. This can be explained by the above-mentioned substrate dependence of the adhesion force.

  18. A novel technique for in situ aggregation of Gluconobacter oxydans using bio-adhesive magnetic nanoparticles

    PubMed Central

    Lu, Huimin; Ni, Kefeng; Wang, Cunxun; Black, Kvar C.L.; Wei, Dongzhi; Ren, Yuhong; Messersmith, Phillip B.

    2012-01-01

    Here, we present a novel technique to immobilize magnetic particles onto whole G. oxydans in situ via a synthetic adhesive biomimetic material inspired by the protein glues of marine mussels. Our approach involves simple coating of a cell adherent polydopamine film onto magnetic nanoparticles, followed by conjugation of the polydopamine-coated nanoparticles to G. oxydans which resulted in cell aggregation. After optimization, 21.3 mg (wet cell weight) G. oxydans per milligram of nanoparticle was aggregated and separated with a magnet. Importantly, the G. oxydan aggregates showed high specific activity and good reusability. The facile approach offers the potential advantages of low cost, easy cell separation, low diffusion resistance and high efficiency. Furthermore, the approach is a convenient platform technique for magnetization of cells in situ by direct mixing of nanoparticles with a cell suspension. PMID:22729662

  19. A review on bioadhesive buccal drug delivery systems: current status of formulation and evaluation methods

    PubMed Central

    Chinna Reddy, P; Chaitanya, K.S.C.; Madhusudan Rao, Y.

    2011-01-01

    Owing to the ease of the administration, the oral cavity is an attractive site for the delivery of drugs. Through this route it is possible to realize mucosal (local effect) and transmucosal (systemic effect) drug administration. In the first case, the aim is to achieve a site-specific release of the drug on the mucosa, whereas the second case involves drug absorption through the mucosal barrier to reach the systemic circulation. The main obstacles that drugs meet when administered via the buccal route derive from the limited absorption area and the barrier properties of the mucosa. The effective physiological removal mechanisms of the oral cavity that take the formulation away from the absorption site are the other obstacles that have to be considered. The strategies studied to overcome such obstacles include the employment of new materials that, possibly, combine mucoadhesive, enzyme inhibitory and penetration enhancer properties and the design of innovative drug delivery systems which, besides improving patient compliance, favor a more intimate contact of the drug with the absorption mucosa. This presents a brief description of advantages and limitations of buccal drug delivery and the anatomical structure of oral mucosa, mechanisms of drug permeation followed by current formulation design in line with developments in buccal delivery systems and methodology in evaluating buccal formulations. PMID:23008684

  20. An atomic charge model for graphene oxide for exploring its bioadhesive properties in explicit water.

    PubMed

    Stauffer, D; Dragneva, N; Floriano, W B; Mawhinney, R C; Fanchini, G; French, S; Rubel, O

    2014-07-28

    Graphene Oxide (GO) has been shown to exhibit properties that are useful in applications such as biomedical imaging, biological sensors, and drug delivery. The binding properties of biomolecules at the surface of GO can provide insight into the potential biocompatibility of GO. Here we assess the intrinsic affinity of amino acids to GO by simulating their adsorption onto a GO surface. The simulation is done using Amber03 force-field molecular dynamics in explicit water. The emphasis is placed on developing an atomic charge model for GO. The adsorption energies are computed using atomic charges obtained from an ab initio electrostatic potential based method. The charges reported here are suitable for simulating peptide adsorption to GO.

  1. Bioadhesion of mussels and geckos: Molecular mechanics, surface chemistry, and nanoadhesives

    NASA Astrophysics Data System (ADS)

    Lee, Haeshin

    The adhesive strategies of living creatures are diverse, ranging from temporary to permanent adhesions with various functions such as locomotion, self-defense, communication, colony formation, and so on. The classic example of temporary adhesion is the gecko, which is known for its ability to walk along vertical and even inverted surfaces; this remarkable adhesion arises from the interfacial weak interactions of van der Waals and capillary forces. In contrast, a celerbrated example of permanent adhesion is found in marine mussels which secrete protein adhesives that function in aqueous environments without mechanical failure against turbulent conditions on the seashore. In addition, mussel adhesives stick to virtually all inorganic and organic surfaces. However, most commonly used man-made adhesives lack such unique adhesion properties compared to their natural counterparts. For example, many commercial adhesives quickly lose their adhesive strength when exposed to solvents, particularly water. The first part of this thesis focused on adhesion mechanics of mussels at a single-molecule level, in which the adhesive molecule showed surprisingly strong yet reversible adhesion on inorganic surfaces but exhibited irreversible covalent bond formation on organic surfaces. Strong and reversible adhesion on mucin surfaces was found, indicating potential application for drug delivery via mucus layers. Next, inspired by the mussel's versatile adhesion on a wide variety of material surfaces, a material-independent surface modification chemistry called 'polydopamine coating' is described. This concept was subsequently adapted to develop a surface-independent polymeric primer for layer-by-layer assembly of multifunctional coatings. Finally, a new bio-hybrid adhesive 'geckel' was developed by the functional combination of adhesion strategies of geckos and mussels. The new bio-inspired adhesive and material-independent surface chemistry can revolutionize the research areas such as medical devices, adhesives, and diagnostics, nanotechnology, biointerface, and catalysis.

  2. An atomic charge model for graphene oxide for exploring its bioadhesive properties in explicit water.

    PubMed

    Stauffer, D; Dragneva, N; Floriano, W B; Mawhinney, R C; Fanchini, G; French, S; Rubel, O

    2014-07-28

    Graphene Oxide (GO) has been shown to exhibit properties that are useful in applications such as biomedical imaging, biological sensors, and drug delivery. The binding properties of biomolecules at the surface of GO can provide insight into the potential biocompatibility of GO. Here we assess the intrinsic affinity of amino acids to GO by simulating their adsorption onto a GO surface. The simulation is done using Amber03 force-field molecular dynamics in explicit water. The emphasis is placed on developing an atomic charge model for GO. The adsorption energies are computed using atomic charges obtained from an ab initio electrostatic potential based method. The charges reported here are suitable for simulating peptide adsorption to GO. PMID:25084935

  3. Localization of the bioadhesive precursors of the sandcastle worm, Phragmatopoma californica (Fewkes).

    PubMed

    Wang, Ching Shuen; Stewart, Russell J

    2012-01-15

    The marine sandcastle worm bonds mineral particles together into underwater composite dwellings with a proteinaceous glue. The products of at least four distinct secretory cell types are co-secreted from the building organ to form the glue. Prominent hetereogeneous granules contain dense sub-granules of Mg and the (polyphospho)proteins Pc3A and B, as well as at least two polybasic proteins, Pc1 and Pc4, as revealed by immunolabeling with specific antibodies against synthetic peptides. Equally prominent homogeneous granules comprise at least two polybasic proteins, Pc2 and Pc5, localized by immunolabeling with anti-synthetic peptide antibodies. The components of the sub-micrometer granule types are unknown, though positive staining with a redox-sensitive dye suggests the contents include o-dihydroxy-phenylalanine (dopa). Quantitative PCR and in situ hybridization demonstrated that a tyrosinase-like enzyme with a signal peptide was highly expressed in both the heterogeneous and homogeneous granules. The contents of the granules are poorly mixed in the secreted mixture that forms the glue. Subsequent covalent cross-linking of the glue may be catalyzed by the co-secreted tyrosinase. The first three parapodia of the sandcastle worm also contain at least two distinct secretory tissues. The Pc4 protein was immunolocalized to the anterior secretory cells and the tryosinase-like gene was expressed in the posterior secretory cells, which suggests these proteins may have multiple roles.

  4. Development and evaluation of buccal bioadhesive tablet of an anti-emetic agent ondansetron.

    PubMed

    Hassan, Nisreen; Khar, R K; Ali, Mushir; Ali, Javed

    2009-01-01

    The aim of the present study was to develop and evaluate a buccal adhesive tablet containing ondansetron hydrochloride (OH). Special punches and dies were fabricated and used while preparing buccal adhesive tablets. The tablets were prepared using carbopol (CP 934), sodium alginate, sodium carboxymethylcellulose low viscosity (SCMC LV), and hydroxypropylmethylcellulose (HPMC 15cps) as mucoadhsive polymers to impart mucoadhesion and ethyl cellulose to act as an impermeable backing layer. The formulations were prepared by direct compression and characterized by different parameters such as weight uniformity, content uniformity, thickness, hardness, swelling index, in vitro drug release studies, mucoadhesive strength, and ex vivo permeation study. As compared with the optimized formulation composed of OH--5 mg, CP 934--30 mg, SCMC LV--165 mg, PEG 6000--40 mg, lactose--5 mg, magnesium stearate--1.5 mg, and aspartame--2 mg, which gave the maximum release (88.15%), non-bitter (OH) that form namely ondansetron base and complexed ondansetron was used in order to make the selected formulation acceptable to human. The result of the in vitro release studies and permeation studies through bovine buccal mucosa revealed that complexed ondansetron gave the maximum release and permeation. The stability of drug in the optimized adhesive tablet was tested for 6 h in natural human saliva; both the drug and device were found to be stable in natural human saliva. Thus, buccal adhesive tablet of ondansetron could be an alternative route to bypass the hepatic first-pass metabolism and to improve the bioavailability of (OH).

  5. Voltage Controller

    NASA Technical Reports Server (NTRS)

    1997-01-01

    Power Efficiency Corporation, specifically formed to manufacture and develop products from NASA technology, has a license to a three-phase power factor controller originally developed by Frank Nola, an engineer at Marshall Space Flight Center. Power Efficiency and two major distributors, Performance Control and Edison Power Technologies, use the electronic control boards to assemble three different motor controllers: Power Commander, Performance Controller, and Energy Master. The company Power Factor Controller reduces excessive energy waste in AC induction motors. It is used in industries and applications where motors operate under variable loads, including elevators and escalators, machine tools, intake and exhaust fans, oil wells, conveyors, pumps, die casting, and compressors. Customer lists include companies such as May Department Stores, Caesars Atlantic City, Ford Motors, and American Axle.

  6. Comparison of the urease test and of direct smear examination in the control of treatment of Helicobacter pylori-induced infection.

    PubMed

    Resende, L M; Queiroz, D M; Mendes, E N; Rocha, G A; Coelho, L G; Passos, M C; Castro, L P; Oliveira, C A; Lima Júnior, G F

    1993-07-01

    The sensitivity and specificity of the preformed urease test and of carbolfuchsin-stained smears for the diagnosis of the presence of Helicobacter pylori in gastric mucosa were evaluated before and after antimicrobial treatment. The results obtained by culture were used as the reference point. We studied 41 patients with endoscopically diagnosed duodenal ulcer. Twenty-five of these were treated with furazolidone (100 mg t.i.d.), amoxicillin (500 mg t.i.d.) and metronidazole (250 mg t.i.d.) for 5 days and then with only furazolidone (100 mg t.i.d.) for an additional 25 days. The 16 control patients were treated with cimetidine (800 mg, 4 times a day). The sensitivity of the urease test and of direct smear examination was 100% before treatment and 84.6% and 92.3%, respectively, after treatment. We conclude that the urease test and carbolfuchsin-stained smears, which are highly sensitive for H. pylori diagnosis, present reduced sensitivity when they are employed for the follow-up of patients treated with antimicrobials.

  7. Validation of housekeeping genes as an internal control for gene expression studies in Giardia lamblia using quantitative real-time PCR.

    PubMed

    Marcial-Quino, Jaime; Fierro, Francisco; De la Mora-De la Mora, Ignacio; Enríquez-Flores, Sergio; Gómez-Manzo, Saúl; Vanoye-Carlo, America; Garcia-Torres, Itzhel; Sierra-Palacios, Edgar; Reyes-Vivas, Horacio

    2016-04-25

    The analysis of transcript levels of specific genes is important for understanding transcriptional regulation and for the characterization of gene function. Real-time quantitative reverse transcriptase PCR (RT-qPCR) has become a powerful tool to quantify gene expression. The objective of this study was to identify reliable housekeeping genes in Giardia lamblia. Twelve genes were selected for this purpose, and their expression was analyzed in the wild type WB strain and in two strains with resistance to nitazoxanide (NTZ) and metronidazole (MTZ), respectively. RefFinder software analysis showed that the expression of the genes is different in the three strains. The integrated data from the four analyses showed that the NADH oxidase (NADH) and aldolase (ALD) genes were the most steadily expressed genes, whereas the glyceraldehyde-3-phosphate dehydrogenase gene was the most unstable. Additionally, the relative expression of seven genes were quantified in the NTZ- and MTZ-resistant strains by RT-qPCR, using the aldolase gene as the internal control, and the results showed a consistent differential pattern of expression in both strains. The housekeeping genes found in this work will facilitate the analysis of mRNA expression levels of other genes of interest in G. lamblia.

  8. Environmental Controls.

    ERIC Educational Resources Information Center

    Schneiderman, Helen, Ed.

    1994-01-01

    Environmental control units, or ECUs, are devices or systems which allow for alternate access to electronic or electrical devices and those objects, like draperies and doors, which may be adapted for use with electricity. Such devices offer the person with a mobility limitation the opportunity to control his or her environment, thus enhancing the…

  9. Cognitive Control

    ERIC Educational Resources Information Center

    Hammond, Kenneth R.; Summers, David A.

    1972-01-01

    Discusses experiments which show difficulties in putting mastered skills to good effect arise through deficiencies of cognitive control: subjects knew what to do but couldn't" do it. Authors believe traditional response-oriented feedback impedes control, hence performance, and that subjects must see why errors are made to improve. (PD)

  10. Control Theory.

    ERIC Educational Resources Information Center

    Toso, Robert B.

    2000-01-01

    Inspired by William Glasser's Reality Therapy ideas, Control Theory (CT) is a disciplinary approach that stresses people's ability to control only their own behavior, based on internal motivations to satisfy five basic needs. At one North Dakota high school, CT-trained teachers are the program's best recruiters. (MLH)

  11. Detonation control

    DOEpatents

    Mace, Jonathan L.; Seitz, Gerald J.; Bronisz, Lawrence E.

    2016-10-25

    Detonation control modules and detonation control circuits are provided herein. A trigger input signal can cause a detonation control module to trigger a detonator. A detonation control module can include a timing circuit, a light-producing diode such as a laser diode, an optically triggered diode, and a high-voltage capacitor. The trigger input signal can activate the timing circuit. The timing circuit can control activation of the light-producing diode. Activation of the light-producing diode illuminates and activates the optically triggered diode. The optically triggered diode can be coupled between the high-voltage capacitor and the detonator. Activation of the optically triggered diode causes a power pulse to be released from the high-voltage capacitor that triggers the detonator.

  12. Under Control.

    ERIC Educational Resources Information Center

    Henry, Rich

    2001-01-01

    Offers advice on how school administrators can properly plan and monitor school construction projects to contain costs. Cost control tips discussed include project scope definition, contract bidding and awarding practice, and project management techniques. (GR)

  13. CONTROL ROD

    DOEpatents

    Zinn, W.H.; Ross, H.V.

    1958-11-18

    A control rod is described for a nuclear reactor. In certaln reactor designs it becomes desirable to use a control rod having great width but relatively llttle thickness. This patent is addressed to such a need. The neutron absorbing material is inserted in a triangular tube, leaving volds between the circular insert and the corners of the triangular tube. The material is positioned within the tube by the use of dummy spacers to achleve the desired absorption pattern, then the ends of the tubes are sealed with suitable plugs. The tubes may be welded or soldered together to form two flat surfaces of any desired width, and covered with sheetmetal to protect the tubes from damage. This design provides a control member that will not distort under the action of outside forces or be ruptured by gases generated within the jacketed control member.

  14. Controlling variability.

    PubMed

    Sanger, Terence D

    2010-11-01

    In human motor control, there is uncertainty in both estimation of initial sensory state and prediction of the outcome of motor commands. With practice, increasing precision can often be achieved, but such precision incurs costs in time, effort, and neural resources. Therefore, motor planning must account for variability, uncertainty, and noise, not just at the endpoint of movement but throughout the movement. The author presents a mathematical basis for understanding the time course of uncertainty during movement. He shows that it is possible to achieve accurate control of the endpoint of a movement even with highly inaccurate and variable controllers. The results provide a first step toward a theory of optimal control for variable, uncertain, and noisy systems that must nevertheless accomplish real-world tasks reliably.

  15. REACTOR CONTROL

    DOEpatents

    Fortescue, P.; Nicoll, D.

    1962-04-24

    A control system employed with a high pressure gas cooled reactor in which a control rod is positioned for upward and downward movement into the neutron field from a position beneath the reactor is described. The control rod is positioned by a coupled piston cylinder releasably coupled to a power drive means and the pressurized coolant is directed against the lower side of the piston. The coolant pressure is offset by a higher fiuid pressure applied to the upper surface of the piston and means are provided for releasing the higher pressure on the upper side of the piston so that the pressure of the coolant drives the piston upwardly, forcing the coupled control rod into the ncutron field of the reactor. (AEC)

  16. Drug Control

    ERIC Educational Resources Information Center

    Leviton, Harvey S.

    1975-01-01

    This article attempts to assemble pertinent information about the drug problem, particularily marihuana. It also focuses on the need for an educational program for drug control with the public schools as the main arena. (Author/HMV)

  17. CONTROL SYSTEM

    DOEpatents

    Shannon, R.H.; Williamson, H.E.

    1962-10-30

    A boiling water type nuclear reactor power system having improved means of control is described. These means include provisions for either heating the coolant-moderator prior to entry into the reactor or shunting the coolantmoderator around the heating means in response to the demand from the heat engine. These provisions are in addition to means for withdrawing the control rods from the reactor. (AEC)

  18. Pain control.

    PubMed

    Boey, W K

    1991-01-01

    There are two components to the perception of pain; the 'sensory' and the 'reactive'. Psychological factors control the latter. Pain research is rapidly advancing: the discovery of endorphins and opioid receptors, the appreciation of the psychological component of pain and the multidisciplinary approach to chronic pain are major advances. Pain can be classified as acute or chronic. Acute pain is easy to diagnose, the cause of pain obvious and the treatment logical, chronic pain has a greater psychological component, is difficult to diagnose and treatment is often empirical. Methods of pain control include drugs, injection techniques, electro stimulation, non invasive therapies, denervation procedures and palliative procedures. A multidisciplinary approach and a combination of methods is necessary to treat chronic pain. Spinal opioids, radiofrequency thermocoagulation, intrapleural bupivacaine, cryoanalgesia and patient controlled analgesia are recent advances in pain control. However, most pain can be controlled adequately with simple methods; what is essential is the interest and commitment of the physician towards achieving optimum therapeutics. PMID:1674199

  19. [New alternatives in the treatment of bacterial vaginosis].

    PubMed

    Luis Arredondo, J; Higuera, F; Narcio, M L; Casanova, G; Beltrán, M

    1994-08-01

    Efficiency and security clindamycin vaginal cream (2%) were compared to oral metronidazole's for the treatment of 184 women with symptomatic bacterial vaginosis in a multicentric, randomized, double-blind, controlled study. The treatment was of 7 days duration, using placebo capsules for the clindamycin group and placebo cream for the metronidazole group. Patients were observed during a follow up (4-13 and 20-43 days after completion of therapy). Global results of this treatment indicated that clindamycin vaginal cream offers a similar efficiency than oral metronidazole. Improvement or total healing was 87% for clindamycin and 79% for metronidazole, with no significant differences (p > 0.22). No relapses were observed in the clindamycin group, and 7% in the metronidazole group. The clindamycin group had a failure rate of 3% compared to 15% in the oral metronidazole group. Both drugs were well tolerated. Side effects more frequently reported were vulvovaginal irritation and cervicitis/vaginitis. The only side effect that could have been classified as serious was a generalized rash in a patient receiving metronidazole. It was concluded that clindamycin vaginal cream (2%) is an efficient and secure alternative to oral metronidazole for the treatment of bacterial vaginosis being the elective therapy for pregnant women in their first gestational trimester. PMID:7959144

  20. Birth Control

    MedlinePlus

    ... your health, frequency of sexual activity, number of sexual partners and desire to have children in the future. Your health care provider can help you select the best form of birth control for you. NIH: National Institute of Child Health and Human Development

  1. Infection Control

    MedlinePlus

    ... These steps are part of infection control. Proper hand washing is the most effective way to prevent the spread of infections in hospitals. If you are a patient, don't be afraid to remind friends, family and health care providers to wash their hands before getting close to you. Other ...

  2. Motor Controllers

    NASA Technical Reports Server (NTRS)

    1984-01-01

    Kollmorgen Corporation's Mermaid II two person submersible is propeller-driven by a system of five DC brushless motors with new electronic controllers that originated in work performed in a NASA/DOE project managed by Lewis Research Center. A key feature of the system is electric commutation rather than mechanical commutation for converting AC current to DC.

  3. Injury Control.

    ERIC Educational Resources Information Center

    Christophersen, Edward R.

    1989-01-01

    Injuries are now the cause of more deaths to children than the next six most frequent causes combined. Reviews the research evidence on the effectiveness of approaches to injury control such as legislation, health education, and behavioral strategies. Suggests avenues of further research. (Author/BJV)

  4. COPD - control drugs

    MedlinePlus

    Chronic obstructive pulmonary disease - control drugs; Bronchodilators - COPD - control drugs; Beta agonist inhaler - COPD - control drugs; Anticholinergic inhaler - COPD - control drugs; Long-acting inhaler - COPD - control drugs; ...

  5. Autonomous control

    NASA Technical Reports Server (NTRS)

    Brown, Barbara

    1990-01-01

    KSC has been developing the Knowledge-Based Autonomous Test Engineer (KATE), which is a tool for performing automated monitoring, diagnosis, and control of electromechanical devices. KATE employs artificial intelligence computing techniques to perform these functions. The KATE system consists of a generic shell and a knowledge base. The KATE shell is the portion of the system which performs the monitoring, diagnosis, and control functions. It is generic in the sense that it is application independent. This means that the monitoring activity, for instance, will be performed with the same algorithms regardless of the particular physical device being used. The knowledge base is the portion of the system which contains specific functional and behavorial information about the physical device KATE is working with. Work is nearing completion on a project at KSC to interface a Texas Instruments Explorer running a LISP version of KATE with a Generic Checkout System (GCS) test-bed to control a physical simulation of a shuttle tanking system (humorously called the Red Wagon because of its color and mobility). The Autonomous Control System (ACS) project supplements and extends the KATE/GCS project by adding three other major activities. The activities include: porting KATE from the Texas Instruments Explorer machine to an Intel 80386-based UNIX workstation in the LISP language; rewriting KATE as necessary to run on the same 80386 workstation but in the Ada language; and investigating software and techniques to translate ANSI Standard Common LISP to Mil Standard Ada. Primary goals of this task are as follows: (1) establish the advantages of using expert systems to provide intelligent autonomous software for Space Station Freedom applications; (2) determine the feasibility of using Ada as the run-time environment for model-based expert systems; (3) provide insight into the advantages and disadvantagesof using LISP or Ada in the run-time environment for expert systems; and (4

  6. Glucose control.

    PubMed

    Preiser, Jean-Charles

    2013-01-01

    Stress-related hyperglycemia is a common finding in acutely ill patients, and is related to the severity and outcome of the critical illness. The pathophysiology of stress hyperglycemia includes hormonal and neural signals, leading to increased production of glucose by the liver and peripheral insulin resistance mediated by the translocation of transmembrane glucose transporters. In one pioneering study, tight glycemic control by intensive insulin therapy in critically ill patients was associated with improved survival. However, this major finding was not confirmed in several other prospective randomized controlled trials. The reasons underlying the discrepancy between the first and the subsequent studies could include nutritional strategy (amount of calories provided, use of parenteral nutrition), case-mix, potential differences in the optimal blood glucose level (BG) in different types of patients, hypoglycemia and its correction, and the magnitude of glucose variability. Therefore, an improved understanding of the physiology and pathophysiology of glycemic regulation during acute illness is needed. Safe and effective glucose control will need improvement in the definition of optimal BG and in the measurement techniques, perhaps including continuous monitoring of insulin algorithms and closed-loop systems. PMID:23075589

  7. Environmental control.

    PubMed

    Squillace, S P

    1992-12-01

    Environmental control measures help eliminate triggers that initiate the allergic reaction and reduce the conditions that sustain it. The most frequent offenders are the ubiquitous dust mites, which are ideally suited to living in the home environment. Control measures consist of minimizing their reservoirs in the patient's bedding, carpets, and upholstered furniture; decreasing humidity; and using acaricides. Cats are the source of another important indoor allergen that becomes and stays airborne as small particles. Removal of the animal (or washing it weekly) and the use of high-efficiency particulate air filters for air ducts and vacuum cleaners are useful in reducing dust mite and cat allergens. Dogs and rodents also produce allergens offensive to the sensitized patient and should be removed or relegated outdoors. Cockroaches have become an increasingly prevalent source of allergens responsible for asthma and rhinitis. Their removal is the focus of research, because current control measures are usually inadequate. Molds, which thrive in any moist environment, produce allergens. Closed windows prevent further influx of outdoor molds and pollens, whereas those harbored indoors, including those residing on plants, should be eliminated.

  8. REACTOR CONTROL

    DOEpatents

    Ruano, W.J.

    1957-12-10

    This patent relates to nuclear reactors of the type which utilize elongited rod type fuel elements immersed in a liquid moderator and shows a design whereby control of the chain reaction is obtained by varying the amount of moderator or reflector material. A central tank for containing liquid moderator and fuel elements immersed therein is disposed within a surrounding outer tank providing an annular space between the two tanks. This annular space is filled with liquid moderator which functions as a reflector to reflect neutrons back into the central reactor tank to increase the reproduction ratio. Means are provided for circulating and cooling the moderator material in both tanks and additional means are provided for controlling separately the volume of moderator in each tank, which latter means may be operated automatically by a neutron density monitoring device. The patent also shows an arrangement for controlling the chain reaction by injecting and varying an amount of poisoning material in the moderator used in the reflector portion of the reactor.

  9. Efficacy of 5-Nitroimidazoles for the Treatment of Giardiasis: A Systematic Review of Randomized Controlled Trials

    PubMed Central

    Deshpande, Abhishek; Thota, Priyaleela; Roman, Yuani; Hernandez, Adrian V.

    2014-01-01

    Background Giardiasis is one of the most common causes of diarrheal disease worldwide and 5-nitroimidazoles (5-NI) are the most commonly prescribed drugs for the treatment of giardiasis. We evaluated the efficacy of 5-nitroimidazoles (5-NI) in the treatment of giardiasis in a systematic review of randomized controlled trials (RCTs). Methodology/Principal Findings We conducted a comprehensive literature search in PubMed-Medline, Scopus, Web of Science and Cochrane Library for RCTs evaluating the efficacy of 5-NI vs. control (placebo or active treatment) on parasitological cure in patients with parasitologically-demonstrated giardiasis. The search was performed in May 2013 with no language restriction by two authors independently. The efficacy outcome was parasitological cure, and harmful outcomes were abdominal pain, bitter or metallic taste, and headache. We included 30 RCTs (n = 3,930). There was a significant and slightly higher response rate with 5-NI in giardiasis treatment (RR 1.06, 95%CI 1.02–1.11, p = 0.005). There was high heterogeneity among studies (I2 = 72%). The response rates for metronidazole, tinidazole and secnidazole were similar (RR 1.05, 95%CI 1.01–1.09, p = 0.01; RR 1.32 95%CI 1.10–1.59, p = 0.003; and RR 1.18 95%CI 0.93–1.449, p = 0.18, respectively). On subgroup analyses, the response rates did not vary substantially and high heterogeneity persisted (I2 = 57%–80%). Harmful outcomes were uncommon, and 5-NIs were associated with lower risk of abdominal pain, and higher risk of both bitter or metallic taste and headache. Conclusions Studies investigating the efficacy of 5-NI in giardiasis treatment are highly heterogeneous. 5-NIs have a slightly better efficacy and worse profile for mild harmful outcomes in the treatment of giardiasis in comparison to controls. Larger high quality RCTs are needed to further assess efficacy and safety profiles of 5-NI. PMID:24625554

  10. Heliostat control

    DOEpatents

    Kaehler, James A.

    1984-01-01

    An improvement in a system and method of controlling heliostat in which the heliostat is operable in azimuth and elevation by respective stepper motors and including the respective steps or means for calculating the position for the heliostat to be at a commanded position, determining the number of steps in azimuth and elevation for each respective motor to get to the commanded position and energizing both the azimuth and elevation stepper motors to run in parallel until predetermined number of steps away from the closest commanded position in azimuth and elevation so that the closest position has been achieved, and thereafter energizing only the remaining motor to bring it to its commanded position. In this way, the heliostat can be started from a stowed position in the morning and operated by a computer means to its commanded position and kept correctly oriented throughout the day using only the time of the day without requiring the usual sensors and feedback apparatus. A computer, or microprocessor, can then control a plurality of many heliostats easily and efficiently throughout the day.

  11. Control apparatus

    NASA Technical Reports Server (NTRS)

    Derkacs, Thomas (Inventor); Fetheroff, Charles W. (Inventor); Matay, Istvan M. (Inventor); Toth, Istvan J. (Inventor)

    1982-01-01

    Although the method and apparatus of the present invention can be utilized to apply either a uniform or a nonuniform covering of material over many different workpieces, the apparatus (20) is advantageously utilized to apply a thermal barrier covering (64) to an airfoil (22) which is used in a turbine engine. The airfoil is held by a gripper assembly (86) while a spray gun (24) is effective to apply the covering over the airfoil. When a portion of the covering has been applied, a sensor (28) is utilized to detect the thickness of the covering. A control apparatus (32) compares the thickness of the covering of material which has been applied with the desired thickness and is subsequently effective to regulate the operation of the spray gun to adaptively apply a covering of a desired thickness with an accuracy of at least plus or minus 0.0015 inches (1.5 mils) despite unanticipated process variations.

  12. 3D graphene oxide-polymer hydrogel: near-infrared light-triggered active scaffold for reversible cell capture and on-demand release.

    PubMed

    Li, Wen; Wang, Jiasi; Ren, Jinsong; Qu, Xiaogang

    2013-12-10

    An active cell scaffold based on a graphene-polymer hydrogel has been successfully fabricated. The macroporous hydrogel can efficiently capture cells not only through the bioadhesive ligand RGD but also through on-demand release of cells with an NIR light stimulus. The latter process shows better dynamic control over cells than traditional passive-hydrogel-based cell depots.

  13. Asthma - control drugs

    MedlinePlus

    Asthma - inhaled corticosteroids; Asthma - long-acting beta-agonists; Asthma - leukotriene modifiers; Asthma - cromolyn; Bronchial asthma-control drugs; Wheezing - control drugs; Reactive airway disease - control drugs

  14. Intelligent control: integrating AI and control theory

    SciTech Connect

    De Jong, K.

    1983-01-01

    The increasing complexity of the requirements placed upon computer-controlled systems is forcing a departure from rigid, predetermined control sequences toward more flexible, intelligent control regimes. The basic premise of this research is that such systems can be developed by exploiting the strengths of both standard control theory and recent developments in artificial intelligence. A framework is described for integrating artificial intelligence (AI) techniques with more traditional control theory approaches both at the design stages as well as online control. Its potential is then discussed in the context of several complex navy control problems including automatic tracking systems, autonomous vehicles, and large-scale, flexible space structures. 8 references.

  15. CONTROL ROOM WITH SPRINKLER SYSTEM CONTROLS, INCLUDING MANUAL CONTROL BOXES ...

    Library of Congress Historic Buildings Survey, Historic Engineering Record, Historic Landscapes Survey

    CONTROL ROOM WITH SPRINKLER SYSTEM CONTROLS, INCLUDING MANUAL CONTROL BOXES FOR THE VENTILATION SYSTEM AND A PLC SWITCH FOR AUTOMATIC CO (CARBON MONOXIDE) SYSTEM. THE AIR TESTING SYSTEM IS FREE STANDING AND THE FANS ARE COMPUTER-OPERATED. - Alaskan Way Viaduct and Battery Street Tunnel, Seattle, King County, WA

  16. Comparative in vitro study of oesophageal adhesiveness of different commercial formulations containing alendronate.

    PubMed

    Shakweh, Monjed; Bravo-Osuna, Irene; Ponchel, Gilles

    2007-08-01

    Cases of oesophageal irritation have been reported in patients ingesting alendronate with little liquid or reclining shortly after taking the medication. Pill-induced oesophagitis principally occurs because of adherence of ingested tablets to the epithelial surface. The objective of this in vitro study was to evaluate the oesophageal bioadhesive characteristics of alendronate generics marketed in Europe, the proprietary Fosamax((R)), one negative and two positive polymer controls. A texture analyser was used for qualitative analysis and to determine the maximal detachment force and the adhesion work developed by each formulation on porcine oesophageal mucosa. Fosamax showed few or no bioadhesive characteristics, but the detachment of few tablets powder particles in some of the experiments does not preclude the potential risk of oesophageal lesions. The 10-mg generic Teva tablets had bioadhesive characteristics similar to a positive control. Other generic formulations (Alenat, Stada, Aliud, Ratiopharm showed "cleavage" rupture, leaving a large piece of the tablet mass attached to the mucosa. The bioadhesive characteristics seem to be related to the inactive ingredients: the presence of adhesive polymers such as HPC or very active disintegration agents, such as sodium croscarmellose. The demonstrated differences in adhesiveness suggest that differences in oesophageal tolerance between Fosamax tablets and generics of sodium alendronate may exist. PMID:17576054

  17. Incoherent control of locally controllable quantum systems

    SciTech Connect

    Dong Daoyi; Zhang Chenbin; Rabitz, Herschel; Pechen, Alexander; Tarn, T.-J.

    2008-10-21

    An incoherent control scheme for state control of locally controllable quantum systems is proposed. This scheme includes three steps: (1) amplitude amplification of the initial state by a suitable unitary transformation, (2) projective measurement of the amplified state, and (3) final optimization by a unitary controlled transformation. The first step increases the amplitudes of some desired eigenstates and the corresponding probability of observing these eigenstates, the second step projects, with high probability, the amplified state into a desired eigenstate, and the last step steers this eigenstate into the target state. Within this scheme, two control algorithms are presented for two classes of quantum systems. As an example, the incoherent control scheme is applied to the control of a hydrogen atom by an external field. The results support the suggestion that projective measurements can serve as an effective control and local controllability information can be used to design control laws for quantum systems. Thus, this scheme establishes a subtle connection between control design and controllability analysis of quantum systems and provides an effective engineering approach in controlling quantum systems with partial controllability information.

  18. Matrix changes due to the toxic effects of metronidazole in intestinal tissue of fish (Onchorhynchus mykiss).

    PubMed

    Gürcü, Beyhan; Koca, Yücel Başımoğlu; Özkut, Mahmud; Tuğlu, Mehmet İbrahim

    2016-02-01

    Metranidazole (MTZ) is an antibiotic used for parasitic infections in a number of species. Accumulation of this drug in the environment and its interaction with fish of economic value makes this drug particularly important. In the present study, we examined the histopathological effects of MTZ on the intestinal tissue of Oncorhynchus mykiss. The fish in aquarium were exposed to MTZ at doses of 5, 10, 20 mg/L for 2, 4 and 8 days. At the end of the experiments, macroscopic pathology or death were not observed at these doses. Histochemical staining with Haematoxylene-Eosin, Periodic Acid Schiff and Gomori Trichrome showed, depending on increased dose and prolonged duration, areas of necrosis, edema, inflammation, small tears at the tips of the villi and excretion with heterogenic distribution of the Goblet cells. Moreover, changes in the connective tissue of the intestines due to toxicity of MTZ and decreases in immunostaining of matrix proteins such as laminin and collagen IV, especially in the epithelium were observed. Findings of the present study would be useful to demonstrate the adverse effects of MTZ use, emphasizing the importance of the effect on fish which could be very important public health.

  19. Neural control: Chaos control sets the pace

    NASA Astrophysics Data System (ADS)

    Schöll, Eckehard

    2010-03-01

    Even simple creatures, such as cockroaches, are capable of complex responses to changes in their environment. But robots usually require complicated dedicated control circuits to perform just a single action. Chaos control theory could allow simpler control strategies to realize more complex behaviour.

  20. Development and Validation of a HPLC Method for the Determination of Cyclosporine A in New Bioadhesive Nanoparticles for Oral Administration

    PubMed Central

    Pecchio, M.; Salman, H.; Irache, J. M.; Renedo, M. J.; Dios-Viéitez, M. C.

    2014-01-01

    A simple and reliable high performance liquid chromatography method was developed and validated for the rapid determination of cyclosporine A in new pharmaceutical dosage forms based on the use of poly (methylvinylether-co-maleic anhydride) nanoparticles. The chromatographic separation was achieved using Ultrabase C18 column (250×4.6 mm, 5 μm), which was kept at 75°. The gradient mobile phase consisted of acetonitrile and water with a flow rate of 1 ml/min. The effluent was monitored at 205 nm using diode array detector. The method exhibited linearity over the assayed concentration range (22-250 μg/ml) and demonstrated good intraday and interday precision and accuracy (relative standard deviations were less than 6.5% and the deviation from theoretical values is below 5.5%). The detection limit was 1.36 μg/ml. This method was also applied for quantitative analysis of cyclosporine A released from poly (methylvinylether-co-maleic anhydride) nanoparticles. PMID:24843186

  1. Non-uniform breaking of molecular bonds, peripheral morphology and releasable adhesion by elastic anisotropy in bio-adhesive contacts

    PubMed Central

    Liu, Yan; Gao, Yanfei

    2015-01-01

    Biological adhesive contacts are usually of hierarchical structures, such as the clustering of hundreds of sub-micrometre spatulae on keratinous hairs of gecko feet, or the clustering of molecular bonds into focal contacts in cell adhesion. When separating these interfaces, releasable adhesion can be accomplished by asymmetric alignment of the lowest scale discrete bonds (such as the inclined spatula that leads to different peeling force when loading in different directions) or by elastic anisotropy. However, only two-dimensional contact has been analysed for the latter method (Chen & Gao 2007 J. Mech. Phys. Solids 55, 1001–1015 (doi:10.1016/j.jmps.2006.10.008)). Important questions such as the three-dimensional contact morphology, the maximum to minimum pull-off force ratio and the tunability of releasable adhesion cannot be answered. In this work, we developed a three-dimensional cohesive interface model with fictitious viscosity that is capable of simulating the de-adhesion instability and the peripheral morphology before and after the onset of instability. The two-dimensional prediction is found to significantly overestimate the maximum to minimum pull-off force ratio. Based on an interface fracture mechanics analysis, we conclude that (i) the maximum and minimum pull-off forces correspond to the largest and smallest contact stiffness, i.e. ‘stiff-adhere and compliant-release’, (ii) the fracture toughness is sensitive to the crack morphology and the initial contact shape can be designed to attain a significantly higher maximum-to-minimum pull-off force ratio than a circular contact, and (iii) since the adhesion is accomplished by clustering of discrete bonds or called bridged crack in terms of fracture mechanics terminology, the above conclusions can only be achieved when the bridging zone is significantly smaller than the contact size. This adhesion-fracture analogy study leads to mechanistic predictions that can be readily used to design biomimetics and releasable adhesives. PMID:25392403

  2. Non-uniform breaking of molecular bonds, peripheral morphology and releasable adhesion by elastic anisotropy in bio-adhesive contacts.

    PubMed

    Liu, Yan; Gao, Yanfei

    2015-01-01

    Biological adhesive contacts are usually of hierarchical structures, such as the clustering of hundreds of sub-micrometre spatulae on keratinous hairs of gecko feet, or the clustering of molecular bonds into focal contacts in cell adhesion. When separating these interfaces, releasable adhesion can be accomplished by asymmetric alignment of the lowest scale discrete bonds (such as the inclined spatula that leads to different peeling force when loading in different directions) or by elastic anisotropy. However, only two-dimensional contact has been analysed for the latter method (Chen & Gao 2007 J. Mech. Phys. Solids 55, 1001-1015 (doi:10.1016/j.jmps.2006.10.008)). Important questions such as the three-dimensional contact morphology, the maximum to minimum pull-off force ratio and the tunability of releasable adhesion cannot be answered. In this work, we developed a three-dimensional cohesive interface model with fictitious viscosity that is capable of simulating the de-adhesion instability and the peripheral morphology before and after the onset of instability. The two-dimensional prediction is found to significantly overestimate the maximum to minimum pull-off force ratio. Based on an interface fracture mechanics analysis, we conclude that (i) the maximum and minimum pull-off forces correspond to the largest and smallest contact stiffness, i.e. 'stiff-adhere and compliant-release', (ii) the fracture toughness is sensitive to the crack morphology and the initial contact shape can be designed to attain a significantly higher maximum-to-minimum pull-off force ratio than a circular contact, and (iii) since the adhesion is accomplished by clustering of discrete bonds or called bridged crack in terms of fracture mechanics terminology, the above conclusions can only be achieved when the bridging zone is significantly smaller than the contact size. This adhesion-fracture analogy study leads to mechanistic predictions that can be readily used to design biomimetics and releasable adhesives.

  3. Superconducting fault current controller/current controller

    DOEpatents

    Cha, Yung S.

    2004-06-15

    A superconducting fault current controller/current controller employs a superconducting-shielded core reactor (SSCR) with a variable impedance in a secondary circuit to control current in a primary circuit such as an electrical distribution system. In a second embodiment, a variable current source is employed in a secondary circuit of an SSCR to control current in the primary circuit. In a third embodiment, both a variable impedance in one secondary circuit and a variable current source in a second circuit of an SSCR are employed for separate and independent control of current in the primary circuit.

  4. Influence of human nail etching for the assessment of topical onychomycosis therapies.

    PubMed

    Repka, Michael A; Mididoddi, Praveen K; Stodghill, Steven P

    2004-09-10

    The purpose of this investigation was to study the physico-chemical properties of hot-melt extruded films containing ketoconazole and to determine the influence of 'nail etching' on film bioadhesion and drug permeability for the assessment of topical onychomycosis therapies. Hot-melt extrusion (HME) was used to prepare films containing 20% w/w ketoconazole. Ketoconazole 0.125% gel was also prepared using Carbopol 974P NF. Films were processed at a temperature range of 115-120 degrees C utilizing a Killion extruder (KLB-100), and were evaluated for post-extrusion drug content, content uniformity, bioadhesion, thermal behavior and nail drug permeation. The extruded films demonstrated excellent content uniformity and post-processing drug content. Tensile and peel tests were recorded to determine the bioadhesive profiles. In this study, work of adhesion and peak adhesive force determinations using the peel tests provided more sensitive results for evaluating the bioadhesivity of the HME films than the tensile tests. The in vitro permeability profiles have demonstrated, that nail samples treated with an 'etchant' demonstrated a significant increase in drug permeability compared to control. Differential scanning calorimetry (DSC) thermograms indicated that ketoconazole was in solid solution within the HME films. These findings are encouraging for the future design and formulation of novel drug delivery systems for the topical treatment of onychomycosis.

  5. Controllability of asynchronous Boolean multiplex control networks

    NASA Astrophysics Data System (ADS)

    Luo, Chao; Wang, Xingyuan; Liu, Hong

    2014-09-01

    In this article, the controllability of asynchronous Boolean multiplex control networks (ABMCNs) is studied. First, the model of Boolean multiplex control networks under Harvey' asynchronous update is presented. By means of semi-tensor product approach, the logical dynamics is converted into linear representation, and a generalized formula of control-depending network transition matrices is achieved. Second, a necessary and sufficient condition is proposed to verify that only control-depending fixed points of ABMCNs can be controlled with probability one. Third, using two types of controls, the controllability of system is studied and formulae are given to show: (a) when an initial state is given, the reachable set at time s under a group of specified controls; (b) the reachable set at time s under arbitrary controls; (c) the specific probability values from a given initial state to destination states. Based on the above formulae, an algorithm to calculate overall reachable states from a specified initial state is presented. Moreover, we also discuss an approach to find the particular control sequence which steers the system between two states with maximum probability. Examples are shown to illustrate the feasibility of the proposed scheme.

  6. Structural Pest Control.

    ERIC Educational Resources Information Center

    Kahn, M. S.; Hoffman, W. M.

    This manual is designed for those who seek certification as pesticide applicators for industrial, institutional, structural, and health-related pest control. It is divided into six sections covering general pest control, wood-destroying organisms, bird control, fumigation, rodent control, and industrial weed control. The manual gives information…

  7. Malagasy Backward Object Control

    ERIC Educational Resources Information Center

    Potsdam, Eric

    2009-01-01

    Backward control is an obligatory interpretational dependency between an overt controller and a nonovert controllee in which the controllee is structurally superior to the controller: "Meg persuaded [Delta]i" ["Roni to give up"]. It contrasts with ordinary forward control, in which the controller is structurally higher: "Meg persuaded Roni"…

  8. ISABELLE control system

    SciTech Connect

    Humphrey, J W; Frankel, R S; Niederer, J A

    1980-01-01

    Design principles for the Brookhaven ISABELLE control intersecting storage ring accelerator are described. Principal features include a locally networked console and control computer complex, a system wide process data highway, and intelligent local device controllers. Progress to date is summarized.

  9. Control System Damps Vibrations

    NASA Technical Reports Server (NTRS)

    Kopf, E. H., Jr.; Brown, T. K.; Marsh, E. L.

    1983-01-01

    New control system damps vibrations in rotating equipment with help of phase-locked-loop techniques. Vibrational modes are controlled by applying suitable currents to drive motor. Control signals are derived from sensors mounted on equipment.

  10. Essure Permanent Birth Control

    MedlinePlus

    ... Implants and Prosthetics Essure Permanent Birth Control Essure Permanent Birth Control Share Tweet Linkedin Pin it More sharing options ... evaluation of the Essure System Essure is a permanent birth control method for women (female sterilization). Implantation of Essure ...

  11. AIR POLLUTION CONTROL TECHNOLOGIES

    EPA Science Inventory

    This is a chapter for John Wiley & Son's Mechanical Engineers' Handbook, and covers issues involving air pollution control. Various technologies for controlling sulfur oxides is considered including fuel desulfurization. It also considers control of nitrogen oxides including post...

  12. Integrated Control Using the SOFFT Control Structure

    NASA Technical Reports Server (NTRS)

    Halyo, Nesim

    1996-01-01

    The need for integrated/constrained control systems has become clearer as advanced aircraft introduced new coupled subsystems such as new propulsion subsystems with thrust vectoring and new aerodynamic designs. In this study, we develop an integrated control design methodology which accomodates constraints among subsystem variables while using the Stochastic Optimal Feedforward/Feedback Control Technique (SOFFT) thus maintaining all the advantages of the SOFFT approach. The Integrated SOFFT Control methodology uses a centralized feedforward control and a constrained feedback control law. The control thus takes advantage of the known coupling among the subsystems while maintaining the identity of subsystems for validation purposes and the simplicity of the feedback law to understand the system response in complicated nonlinear scenarios. The Variable-Gain Output Feedback Control methodology (including constant gain output feedback) is extended to accommodate equality constraints. A gain computation algorithm is developed. The designer can set the cross-gains between two variables or subsystems to zero or another value and optimize the remaining gains subject to the constraint. An integrated control law is designed for a modified F-15 SMTD aircraft model with coupled airframe and propulsion subsystems using the Integrated SOFFT Control methodology to produce a set of desired flying qualities.

  13. Multi-institution case–control and cohort study of risk factors for the development and mortality of Clostridium difficile infections in Japan

    PubMed Central

    Takahashi, Masahiko; Mori, Nobuaki; Bito, Seiji

    2014-01-01

    Objective To examine risk factors for Clostridium difficile infection (CDI) morbidity and mortality in Japan. Design Multimethod investigation including a case–control study and cohort study. Setting 47 participating facilities of the National Hospital Organization (NHO). Participants 1026 patients with CDI and 878 patients in the control group over the age of 18 years admitted to the subject NHO facilities from November 2010 to October 2011. Main outcome measures In a case–control study, we identify risk factors for CDI development. Next, in a cohort study, we identify risk factors for all-cause mortality within 30 days following CDI onset. Results A total of 1026 cases of CDI meeting the definitions of this investigation were identified, encompassing 878 patients at 42 of the 47 subject facilities. In the case–control study, we identified, compared with no antibiotics use, use of first-generation and second-generation cephem antibiotics (OR 1.44; 95% CI 1.10 to 1.87), use of third-generation and fourth-generation cephem antibiotics (OR 1.86; 95% CI 1.48 to 2.33) and use of carbapenem antibiotics (OR 1.87; 95% CI 1.44 to 2.42) the risk factors for CDI development. However, use of penicillin was not identified as a risk factor. In the cohort study, sufficient data for analysis was available for 924 CDI cases; 102 of them (11.0%) resulted in death within 30 days of CDI onset. Compared with no anti-CDI drug use, use of vancomycin was associated with reduced risk of mortality (OR 0.43; 95% CI 0.25 to 0.75) whereas metronidazole was not. Conclusions The findings mirror those of previous studies from Europe and North America, identifying the administration of broad-spectrum antibiotics as a risk factor for CDI development. The use of vancomycin is associated with a decreased risk of mortality. PMID:25186155

  14. Anticipatory Neurofuzzy Control

    NASA Technical Reports Server (NTRS)

    Mccullough, Claire L.

    1994-01-01

    Technique of feedback control, called "anticipatory neurofuzzy control," developed for use in controlling flexible structures and other dynamic systems for which mathematical models of dynamics poorly known or unknown. Superior ability to act during operation to compensate for, and adapt to, errors in mathematical model of dynamics, changes in dynamics, and noise. Also offers advantage of reduced computing time. Hybrid of two older fuzzy-logic control techniques: standard fuzzy control and predictive fuzzy control.

  15. Biological Control in Agroecosystems

    NASA Astrophysics Data System (ADS)

    Batra, Suzanne W. T.

    1982-01-01

    Living organisms are used as biological pest control agents in (i) classical biological control, primarily for permanent control of introduced perennial weed pests or introduced pests of perennial crops; (ii) augmentative biological control, for temporary control of native or introduced pests of annual crops grown in monoculture; and (iii) conservative or natural control, in which the agroecosystem is managed to maximize the effect of native or introduced biological control agents. The effectiveness of biological control can be improved if it is based on adequate ecological information and theory, and if it is integrated with other pest management practices.

  16. CONTROL LIMITER DEVICE

    DOEpatents

    DeShong, J.A.

    1960-03-01

    A control-limiting device for monltoring a control system is described. The system comprises a conditionsensing device, a condition-varying device exerting a control over the condition, and a control means to actuate the condition-varying device. A control-limiting device integrates the total movement or other change of the condition-varying device over any interval of time during a continuum of overlapping periods of time, and if the tothl movement or change of the condition-varying device exceeds a preset value, the control- limiting device will switch the control of the operated apparatus from automatic to manual control.

  17. Unfalsified control based on the ? controller parameterisation

    NASA Astrophysics Data System (ADS)

    Sánchez-Peña, R. S.; Colmegna, P.; Bianchi, F.

    2015-11-01

    This paper presents an implementation of the unfalsified control (UC) method using the Riccati-based parameterisation of ? controllers. The method provides an infinite controller set to (un)falsify the real-time data streams seeking for the best performance. Different sets may be designed to increase the degrees of freedom of the set of controller candidates to perform UC. In general, a set of m central controllers could be designed, each one seeking different objectives and all with their own parameterisation as a function of a stable and bounded transfer matrix. For example, one controller parameterisation could be designed to solve the robust stability of a model set which covers the physical system, therefore guaranteeing feasibility. The implementation requires the online optimisation of either quadratic fractional or quadratic problems, depending on the selection of the cost function. A multi-input, multi-output (MIMO) time-varying model of a permanent magnet synchronous generator illustrates the use of this technique.

  18. Minimal control power of the controlled teleportation

    NASA Astrophysics Data System (ADS)

    Jeong, Kabgyun; Kim, Jaewan; Lee, Soojoon

    2016-03-01

    We generalize the control power of a perfect controlled teleportation of an entangled three-qubit pure state, suggested by Li and Ghose [Phys. Rev. A 90, 052305 (2014), 10.1103/PhysRevA.90.052305], to the control power of a general controlled teleportation of a multiqubit pure state. Thus, we define the minimal control power, and calculate the values of the minimal control power for a class of general three-qubit Greenberger-Horne-Zeilinger (GHZ) states and the three-qubit W class whose states have zero three-tangles. Moreover, we show that the standard three-qubit GHZ state and the standard three-qubit W state have the maximal values of the minimal control power for the two classes, respectively. This means that the minimal control power can be interpreted as not only an operational quantity of a three-qubit quantum communication but also a degree of three-qubit entanglement. In addition, we calculate the values of the minimal control power for general n -qubit GHZ states and the n -qubit W -type states.

  19. Improving Control of Two Motor Controllers

    NASA Technical Reports Server (NTRS)

    Toland, Ronald W.

    2004-01-01

    A computer program controls motors that drive translation stages in a metrology system that consists of a pair of two-axis cathetometers. This program is specific to Compumotor Gemini (or equivalent) motors and the Compumotor 6K-series (or equivalent) motor controller. Relative to the software supplied with the controller, this program affords more capabilities and is easier to use. Written as a Virtual Instrument in the LabVIEW software system, the program presents an imitation control panel that the user can manipulate by use of a keyboard and mouse. There are three modes of operation: command, movement, and joystick. In command mode, single commands are sent to the controller for troubleshooting. In movement mode, distance, speed, and/or acceleration commands are sent to the controller. Position readouts from the motors and from position encoders on the translation stages are displayed in marked fields. At any time, the position readouts can be recorded in a file named by the user. In joystick mode, the program yields control of the motors to a joystick. The program sends commands to, and receives data from, the controller via a serial cable connection, using the serial-communication portion of the software supplied with the controller.

  20. Aircraft adaptive learning control

    NASA Technical Reports Server (NTRS)

    Lee, P. S. T.; Vanlandingham, H. F.

    1979-01-01

    The optimal control theory of stochastic linear systems is discussed in terms of the advantages of distributed-control systems, and the control of randomly-sampled systems. An optimal solution to longitudinal control is derived and applied to the F-8 DFBW aircraft. A randomly-sampled linear process model with additive process and noise is developed.

  1. Manual on Bibliographic Control.

    ERIC Educational Resources Information Center

    International Federation of Library Associations, The Hague (Netherlands).

    This manual outlines objectives, functions, and methods for establishing national bibliographic control as part of the development of a worldwide system for the control and exchange of bibliographic information. Chapters cover: (1) definitions of bibliographic control and related concepts including Universal Bibliographic Control (UBC) and…

  2. Control augmentation for lateral control wheel steering

    NASA Technical Reports Server (NTRS)

    Foulkes, R. H., Jr.

    1981-01-01

    Flight control system design for lateral control wheel steering is discussed. Two alternate designs are presented. The first design is a roll-rate command, bank-angle hold system with a wings-level track-hold submode. The second is a curved-track-hold system. Design details and real-time flight simulator results are included.

  3. Chaotic neural control

    NASA Astrophysics Data System (ADS)

    Potapov, A.; Ali, M. K.

    2001-04-01

    We consider the problem of stabilizing unstable equilibria by discrete controls (the controls take discrete values at discrete moments of time). We prove that discrete control typically creates a chaotic attractor in the vicinity of an equilibrium. Artificial neural networks with reinforcement learning are known to be able to learn such a control scheme. We consider examples of such systems, discuss some details of implementing the reinforcement learning to controlling unstable equilibria, and show that the arising dynamics is characterized by positive Lyapunov exponents, and hence is chaotic. This chaos can be observed both in the controlled system and in the activity patterns of the controller.

  4. HYDRAULIC SERVO CONTROL MECHANISM

    DOEpatents

    Hussey, R.B.; Gottsche, M.J. Jr.

    1963-09-17

    A hydraulic servo control mechanism of compact construction and low fluid requirements is described. The mechanism consists of a main hydraulic piston, comprising the drive output, which is connected mechanically for feedback purposes to a servo control piston. A control sleeve having control slots for the system encloses the servo piston, which acts to cover or uncover the slots as a means of controlling the operation of the system. This operation permits only a small amount of fluid to regulate the operation of the mechanism, which, as a result, is compact and relatively light. This mechanism is particuiarly adaptable to the drive and control of control rods in nuclear reactors. (auth)

  5. An intelligent traffic controller

    SciTech Connect

    Kagolanu, K.; Fink, R.; Smartt, H.; Powell, R.; Larsen, E.

    1995-12-01

    A controller with advanced control logic can significantly improve traffic flows at intersections. In this vein, this paper explores fuzzy rules and algorithms to improve the intersection operation by rationalizing phase changes and green times. The fuzzy logic for control is enhanced by the exploration of neural networks for families of membership functions and for ideal cost functions. The concepts of fuzzy logic control are carried forth into the controller architecture. Finally, the architecture and the modules are discussed. In essence, the control logic and architecture of an intelligent controller are explored.

  6. Nuclear reactor control apparatus

    DOEpatents

    Sridhar, Bettadapur N.

    1983-11-01

    Nuclear reactor core safety rod release apparatus comprises a control rod having a detent notch in the form of an annular peripheral recess at its upper end, a control rod support tube for raising and lowering the control rod under normal conditions, latches pivotally mounted on the control support tube with free ends thereof normally disposed in the recess in the control rod, and cam means for pivoting the latches out of the recess in the control rod when a scram condition occurs. One embodiment of the invention comprises an additional magnetically-operated latch for releasing the control rod under two different conditions, one involving seismic shock.

  7. Fuzzy and neural control

    NASA Technical Reports Server (NTRS)

    Berenji, Hamid R.

    1992-01-01

    Fuzzy logic and neural networks provide new methods for designing control systems. Fuzzy logic controllers do not require a complete analytical model of a dynamic system and can provide knowledge-based heuristic controllers for ill-defined and complex systems. Neural networks can be used for learning control. In this chapter, we discuss hybrid methods using fuzzy logic and neural networks which can start with an approximate control knowledge base and refine it through reinforcement learning.

  8. TFTR diagnostic vacuum controller

    SciTech Connect

    Olsen, D.; Persons, R.

    1981-01-01

    The TFTR diagnostic vacuum controller (DVC) provides in conjunction with the Central Instrumentation Control and Data Acquisition System (CICADA), control and monitoring for the pumps, valves and gauges associated with each individual diagnostic vacuum system. There will be approximately 50 systems on TFTR. Two standard versions of the controller (A and B) wil be provided in order to meet the requirements of two diagnostic manifold arrangements. All pump and valve sequencing, as well as protection features, will be implemented by the controller.

  9. Generic device controller for accelerator control systems

    SciTech Connect

    Mariotti, R.; Buxton, W.; Frankel, R.; Hoff, L.

    1987-01-01

    A new distributed intelligence control system has become operational at the AGS for transport, injection, and acceleration of heavy ions. A brief description of the functionality of the physical devices making up the system is given. An attempt has been made to integrate the devices for accelerator specific interfacing into a standard microprocessor system, namely, the Universal Device Controller (UDC). The main goals for such a generic device controller are to provide: local computing power; flexibility to configure; and real time event handling. The UDC assemblies and software are described. (LEW)

  10. SODR Memory Control Buffer Control ASIC

    NASA Technical Reports Server (NTRS)

    Hodson, Robert F.

    1994-01-01

    The Spacecraft Optical Disk Recorder (SODR) is a state of the art mass storage system for future NASA missions requiring high transmission rates and a large capacity storage system. This report covers the design and development of an SODR memory buffer control applications specific integrated circuit (ASIC). The memory buffer control ASIC has two primary functions: (1) buffering data to prevent loss of data during disk access times, (2) converting data formats from a high performance parallel interface format to a small computer systems interface format. Ten 144 p in, 50 MHz CMOS ASIC's were designed, fabricated and tested to implement the memory buffer control function.

  11. Control rod drive

    DOEpatents

    Hawke, Basil C.

    1986-01-01

    A control rod drive uses gravitational forces to insert one or more control rods upwardly into a reactor core from beneath the reactor core under emergency conditions. The preferred control rod drive includes a vertically movable weight and a mechanism operatively associating the weight with the control rod so that downward movement of the weight is translated into upward movement of the control rod. The preferred control rod drive further includes an electric motor for driving the control rods under normal conditions, an electrically actuated clutch which automatically disengages the motor during a power failure and a decelerator for bringing the control rod to a controlled stop when it is inserted under emergency conditions into a reactor core.

  12. Boiler control systems engineering

    SciTech Connect

    Gilman, J.

    2005-07-01

    The book provides in-depth coverage on how to safely and reliably control the firing of a boiler. Regardless of the capacity or fuel, certain fundamental control systems are required for boiler control. Large utility systems are more complex due to the number of burners and the overall capacity and equipment. This book covers engineering details on control systems and provides specific examples of boiler control including configuration and tuning. References to requirements are based on the 2004 NFPA 85 along with other ISA standards. Detailed chapters cover: Boiler fundamentals including piping and instrument diagrams (P&IDs) and a design basis checklist; Control of boilers, from strategies and bumpless transfer to interlock circuitry and final control elements; Furnace draft; Feedwater; Coal-fired boilers; Fuel and air control; Steam temperature; Burner management systems; Environment; and Control valve sizing. 2 apps.

  13. Spacecraft stability and control

    NASA Technical Reports Server (NTRS)

    Barret, Chris

    1992-01-01

    The Earth's first artificial satellite, Sputnik 1, slowly tumbled in orbit. The first U.S. satellite, Explorer 1, also tumbled out of control. Today, satellite stability and control has become a higher priority. For a satellite design that is to have a life expectancy of 14 years, appropriate spacecraft flight control systems will be reviewed, stability requirements investigated, and an appropriate flight control system recommended in order to see the design process. Disturbance torques, including aerodynamic, magnetic, gravity gradient, solar, micrometeorite, debris, collision, and internal torques, will be assessed to quantify the disturbance environment so that the required compensating torques can be determined. The control torques, including passive versus active, momentum control, bias momentum, spin stabilization, dual spin, gravity gradient, magnetic, reaction wheels, control moment gyros, inertia augmentation techniques, three-axis control, and reaction control systems (RCSs), will be considered. Conditions for stability will also be considered.

  14. PDX diagnostic control system

    SciTech Connect

    Mika, R.

    1981-01-01

    This paper describes a computer-base diagnostic control system operating on the PDX Tokamak. The prime function of the system is to control mechanical positioning devices associated with various diagnostics including Thomson Scattering, X-Ray Pulse Height Analyzer, Rotating Scanning Monochromator, Fast Ion Detection Experiment, Bolometers and Plasma Limiters. The diagnostic control system consists of a PDP-11/34 computer, a CAMAC system partitioned between the PDX control room and the PDX machine area, and special electronic control modules developed at PPL. The special modules include a digital closed loop motor controller and user interface control panel for control and status display. A standard control panel was developed for interfacing each system user with the PDP-11/34 computer, through specially developed CAMAC modules.

  15. Segment alignment control system

    NASA Technical Reports Server (NTRS)

    Aubrun, JEAN-N.; Lorell, Ken R.

    1988-01-01

    The segmented primary mirror for the LDR will require a special segment alignment control system to precisely control the orientation of each of the segments so that the resulting composite reflector behaves like a monolith. The W.M. Keck Ten Meter Telescope will utilize a primary mirror made up of 36 actively controlled segments. Thus the primary mirror and its segment alignment control system are directly analogous to the LDR. The problems of controlling the segments in the face of disturbances and control/structures interaction, as analyzed for the TMT, are virtually identical to those for the LDR. The two systems are briefly compared.

  16. Control system design method

    DOEpatents

    Wilson, David G.; Robinett, III, Rush D.

    2012-02-21

    A control system design method and concomitant control system comprising representing a physical apparatus to be controlled as a Hamiltonian system, determining elements of the Hamiltonian system representation which are power generators, power dissipators, and power storage devices, analyzing stability and performance of the Hamiltonian system based on the results of the determining step and determining necessary and sufficient conditions for stability of the Hamiltonian system, creating a stable control system based on the results of the analyzing step, and employing the resulting control system to control the physical apparatus.

  17. Aircraft control system

    NASA Technical Reports Server (NTRS)

    Kendall, Greg T. (Inventor); Morgan, Walter R. (Inventor)

    2010-01-01

    A span-loaded, highly flexible flying wing, having horizontal control surfaces mounted aft of the wing on extended beams to form local pitch-control devices. Each of five spanwise wing segments of the wing has one or more motors and photovoltaic arrays, and produces its own lift independent of the other wing segments, to minimize inter-segment loads. Wing dihedral is controlled by separately controlling the local pitch-control devices consisting of a control surface on a boom, such that inboard and outboard wing segment pitch changes relative to each other, and thus relative inboard and outboard lift is varied.

  18. Wing Flutter Control

    NASA Technical Reports Server (NTRS)

    1997-01-01

    Through Small Business Innovation Research (SBIR) contracts from Langley Research Center, Orbital Research Inc. developed the Orbital Research Intelligent Control Algorithm (ORICA), the first practical hardware-independent adaptive predictive control structure, specifically suited for optimal control of complex, time-varying systems. ORICA technology has been applied to the problem of controlling aircraft wing flutter. Coupled with NASA expertise, the technology has the possibility of making jet travel safer, more cost effective by extending distance range, and lowering overall aircraft operating costs. Future application areas for ORICA include control of robots, power trains, systems with arrays of sensors, or regulating chemical plants or electrical power plant control.

  19. CONTROL ROD DRIVE

    DOEpatents

    Chapellier, R.A.; Rogers, I.

    1961-06-27

    Accurate and controlled drive for the control rod is from an electric motor. A hydraulic arrangement is provided to balance a piston against which a control rod is urged by the application of fluid pressure. The electric motor drive of the control rod for normal operation is made through the aforementioned piston. In the event scramming is required, the fluid pressure urging the control rod against the piston is relieved and an opposite fluid pressure is applied. The lack of mechanical connection between the electric motor and control rod facilitates the scramming operation.

  20. Programmable Digital Controller

    NASA Technical Reports Server (NTRS)

    Wassick, Gregory J.

    2012-01-01

    An existing three-channel analog servo loop controller has been redesigned for piezoelectric-transducer-based (PZT-based) etalon control applications to a digital servo loop controller. This change offers several improvements over the previous analog controller, including software control over proportional-integral-derivative (PID) parameters, inclusion of other data of interest such as temperature and pressure in the control laws, improved ability to compensate for PZT hysteresis and mechanical mount fluctuations, ability to provide pre-programmed scanning and stepping routines, improved user interface, expanded data acquisition, and reduced size, weight, and power.

  1. Towards autonomous fuzzy control

    NASA Technical Reports Server (NTRS)

    Shenoi, Sujeet; Ramer, Arthur

    1993-01-01

    The efficient implementation of on-line adaptation in real time is an important research problem in fuzzy control. The goal is to develop autonomous self-organizing controllers employing system-independent control meta-knowledge which enables them to adjust their control policies depending on the systems they control and the environments in which they operate. An autonomous fuzzy controller would continuously observe system behavior while implementing its control actions and would use the outcomes of these actions to refine its control policy. It could be designed to lie dormant when its control actions give rise to adequate performance characteristics but could rapidly and autonomously initiate real-time adaptation whenever its performance degrades. Such an autonomous fuzzy controller would have immense practical value. It could accommodate individual variations in system characteristics and also compensate for degradations in system characteristics caused by wear and tear. It could also potentially deal with black-box systems and control scenarios. On-going research in autonomous fuzzy control is reported. The ultimate research objective is to develop robust and relatively inexpensive autonomous fuzzy control hardware suitable for use in real time environments.

  2. Advanced Emissions Control Development Program: Mercury Control

    SciTech Connect

    Evans, A.P.; Redinger, K.W.; Holmes, M.J.

    1997-07-01

    McDermott Technology, Inc. (a subsidiary of Babcock & Wilcox) is conducting the Advanced Emissions Control Development Project (AECDP) which is aimed at the development of practical, cost-effective strategies for reducing the emissions of hazardous air pollutants (HAPS) from coal-fired electric utility plants. The need for such controls may arise as the US Environmental Protection Agency (EPA) proceeds with implementation of requirements set forth in the Clean Air Act Amendments (CAAA`s) of 1990. Promulgation of air toxics emissions regulations for electric utility plants could dramatically impact utilities burning coal, their industrial and residential customers, and the coal industry. AECDP project work will supply the information needed by utilities to respond to potential HAPs regulations in a timely, cost-effective, enviromnentally-sound manner which supports the continued use of the Nation`s abundant reserves of coal, such as those in the State of Ohio. The development work is being carried out using the 10 MW Clean Environment Development Facility wherein air toxics emissions control strategies can be developed under controlled conditions. The specific objectives of the project are to (1) measure and understand production and partitioning of air toxics species for a variety of coals, (2) optimize the air toxics removal performance of conventional flue gas cleanup systems, (3) develop advanced air toxics emissions control concepts, (4) develop and validate air toxics emissions measurement and monitoring techniques, and (5) establish a comprehensive, self-consistent air toxics data library. This project is supported by the Department of Energy, the Ohio Coal Development Office within the Ohio Department of Development and Babcock & Wilcox. A comprehensive assessment of HAP emissions from coal-fired electric utility boilers sponsored by the Department of Energy and the Electric Power Research Institute concluded that with the exception of selenium and mercury

  3. ENGINEERING CONTROL INTO MEDICINE

    PubMed Central

    Stone, David J.; Celi, Leo Anthony; Csete, Marie

    2015-01-01

    The human body is a tightly controlled engineering miracle. However, medical training generally does not cover ‘control’ (in the engineering sense) in physiology, pathophysiology and therapeutics. A better understanding of how evolved controls maintain normal homeostasis is critical for understanding the failure mode of controlled systems, i.e., disease. We believe that teaching and research must incorporate an understanding of the control systems in physiology, and take advantage of the quantitative tools used by engineering to understand complex systems. Control systems are ubiquitous in physiology, though often unrecognized. Here we provide selected examples of the role of control in physiology (heart rate variability, immunity), pathophysiology (inflammation in sepsis), and therapeutic devices (diabetes and the artificial pancreas). We also present a high level background to the concept of robustly controlled systems and examples of clinical insights using the controls framework. PMID:25680579

  4. Milton controller introduced.

    PubMed

    2002-11-01

    Hamworthy Heating has recently introduced the Milton boiler sequence controller, a microprocessor based control system designed for use with Hamworthy Sherborne modulating boilers and the newly launched Wessex 220M Series of fully modulating boilers. PMID:12472058

  5. Birth control pills - combination

    MedlinePlus

    ... use another birth control method (condom, diaphragm, or sponge) for the next 7 days. This is called ... of birth control, such as condom, diaphragm, or sponge if: You miss 1 or more pills. You ...

  6. Linear decentralized learning control

    NASA Technical Reports Server (NTRS)

    Lee, Soo C.; Longman, Richard W.; Phan, Minh

    1992-01-01

    The new field of learning control develops controllers that learn to improve their performance at executing a given task, based on experience performing this task. The simplest forms of learning control are based on the same concept as integral control, but operating in the domain of the repetitions of the task. This paper studies the use of such controllers in a decentralized system, such as a robot with the controller for each link acting independently. The basic result of the paper is to show that stability of the learning controllers for all subsystems when the coupling between subsystems is turned off, assures stability of the decentralized learning in the coupled system, provided that the sample time in the digital learning controller is sufficiently short.

  7. SETI data controllers

    NASA Technical Reports Server (NTRS)

    Gosline, R. M.

    1988-01-01

    Three data controllers developed for the SETI project are described. Two are used primarily for recording and playback of SETI data from the Radio Science Surveillance System (RSSS). The third is used as a SETI station controller for DSS 13.

  8. Birth Control Patch

    MedlinePlus

    ... control the functioning of the body's organs. How Does It Work? The combination of the hormones progesterone ... absorbed by the skin.) previous continue How Well Does It Work? Ongoing studies suggest the birth control ...

  9. Nutrient Control Design Manual

    EPA Science Inventory

    The Nutrient Control Design Manual will present an extensive state-of-the-technology review of the engineering design and operation of nitrogen and phosphorous control technologies and techniques applied at municipal wastewater treatment plants (WWTPs). This manual will present ...

  10. Nutrient Control Seminars

    EPA Science Inventory

    These Nutrient Control Seminars will present an extensive state-of-the-technology review of the engineering design and operation of nitrogen and phosphorous control technologies and techniques applied at municipal wastewater treatment plants (WWTPs). These seminars will present ...

  11. Microtron Modelling and Control

    SciTech Connect

    Krist, Pavel; Bila, Jiri

    2010-01-05

    The article describes the design of the mathematical model and automatic control system of the microtron (high frequency cyclic electron accelerator). This type of accelerator was controlled manually till now. The critical values have been set up empirically on the basis of the previous operational experiences. The designed automatic control system with fuzzy controller should increase the accelerated electrons current value and improve the beam stability.

  12. MEANS FOR CONTROLLING REACTIONS

    DOEpatents

    Nordheim, L.W.; Wigner, E.P.

    1961-06-27

    The patented means is described for controlling a nuclear reactor which comprises a tank containing a dispersion of a thermally fissionable material in a liquid moderator and a material convertible to a thermally fissionable material in a container disposed about the tank. The control means comprises a control rod chamber, containing only a liquid moderator, disposed within the container and adjacent to the tank and a control rod designed to be inserted into the chamber.

  13. System for controlling apnea

    SciTech Connect

    Holzrichter, John F

    2015-05-05

    An implanted stimulation device or air control device are activated by an external radar-like sensor for controlling apnea. The radar-like sensor senses the closure of the air flow cavity, and associated control circuitry signals (1) a stimulator to cause muscles to open the air passage way that is closing or closed or (2) an air control device to open the air passage way that is closing or closed.

  14. Statistical process control

    SciTech Connect

    Oakland, J.S.

    1986-01-01

    Addressing the increasing importance for firms to have a thorough knowledge of statistically based quality control procedures, this book presents the fundamentals of statistical process control (SPC) in a non-mathematical, practical way. It provides real-life examples and data drawn from a wide variety of industries. The foundations of good quality management and process control, and control of conformance and consistency during production are given. Offers clear guidance to those who wish to understand and implement modern SPC techniques.

  15. Adaptive, predictive controller for optimal process control

    SciTech Connect

    Brown, S.K.; Baum, C.C.; Bowling, P.S.; Buescher, K.L.; Hanagandi, V.M.; Hinde, R.F. Jr.; Jones, R.D.; Parkinson, W.J.

    1995-12-01

    One can derive a model for use in a Model Predictive Controller (MPC) from first principles or from experimental data. Until recently, both methods failed for all but the simplest processes. First principles are almost always incomplete and fitting to experimental data fails for dimensions greater than one as well as for non-linear cases. Several authors have suggested the use of a neural network to fit the experimental data to a multi-dimensional and/or non-linear model. Most networks, however, use simple sigmoid functions and backpropagation for fitting. Training of these networks generally requires large amounts of data and, consequently, very long training times. In 1993 we reported on the tuning and optimization of a negative ion source using a special neural network[2]. One of the properties of this network (CNLSnet), a modified radial basis function network, is that it is able to fit data with few basis functions. Another is that its training is linear resulting in guaranteed convergence and rapid training. We found the training to be rapid enough to support real-time control. This work has been extended to incorporate this network into an MPC using the model built by the network for predictive control. This controller has shown some remarkable capabilities in such non-linear applications as continuous stirred exothermic tank reactors and high-purity fractional distillation columns[3]. The controller is able not only to build an appropriate model from operating data but also to thin the network continuously so that the model adapts to changing plant conditions. The controller is discussed as well as its possible use in various of the difficult control problems that face this community.

  16. Robust control of accelerators

    SciTech Connect

    Johnson, W.J.D. ); Abdallah, C.T. )

    1990-01-01

    The problem of controlling the variations in the rf power system can be effectively cast as an application of modern control theory. Two components of this theory are obtaining a model and a feedback structure. The model inaccuracies influence the choice of a particular controller structure. Because of the modeling uncertainty, one has to design either a variable, adaptive controller or a fixed, robust controller to achieve the desired objective. The adaptive control scheme usually results in very complex hardware; and, therefore, shall not be pursued in this research. In contrast, the robust control methods leads to simpler hardware. However, robust control requires a more accurate mathematical model of the physical process than is required by adaptive control. Our research at the Los Alamos National Laboratory (LANL) and the University of New Mexico (UNM) has led to the development and implementation of a new robust rf power feedback system. In this paper, we report on our research progress. In section one, the robust control problem for the rf power system and the philosophy adopted for the beginning phase of our research is presented. In section two, the results of our proof-of-principle experiments are presented. In section three, we describe the actual controller configuration that is used in LANL FEL physics experiments. The novelty of our approach is that the control hardware is implemented directly in rf without demodulating, compensating, and then remodulating.

  17. Finite Control in Korean

    ERIC Educational Resources Information Center

    Lee, Kum Young

    2009-01-01

    This thesis explores finite control in Korean. An overview of the previous studies of control shows that the mainstream literature on control has consistently argued that referential dependence between an overt matrix argument and an embedded null subject is characteristic of non-finite clauses which contain a PRO subject. Moreover, although some…

  18. Floating Point Control Library

    2007-08-02

    Floating Point Control is a Library that allows for the manipulation of floating point unit exception masking funtions control exceptions in both the Streaming "Single Instruction, Multiple Data" Extension 2 (SSE2) unit and the floating point unit simultaneously. FPC also provides macros to set floating point rounding and precision control.

  19. Intermittent Control Systems

    ERIC Educational Resources Information Center

    Montgomery, Thomas L.; And Others

    1975-01-01

    The technique of intermittent control systems for air quality control as developed and used by the Tennessee Valley Authority is investigated. Although controversial, all Tennessee Valley Authority sulfur dioxide elimination programs are scheduled to be operational this year. Existing or anticipated intermittent control systems are identified. (BT)

  20. Importance of controls

    SciTech Connect

    Schilling, J.

    1995-08-01

    The importance of NO{sub x} boiler control methods is outlined: the following topics are discussed: boiler problems; environmental problems; NO{sub x} control methods; low excess air control; low NO{sub x} burners; flue gas recirculation; staged air combustion; fuel reburning; switching/dual fuels; selective non-catalytic reduction (SNCR); and selective catalytic reduction (SCR). Final recommendations are presented.

  1. Indirect decentralized learning control

    NASA Technical Reports Server (NTRS)

    Longman, Richard W.; Lee, Soo C.; Phan, M.

    1992-01-01

    The new field of learning control develops controllers that learn to improve their performance at executing a given task, based on experience performing this specific task. In a previous work, the authors presented a theory of indirect learning control based on use of indirect adaptive control concepts employing simultaneous identification and control. This paper develops improved indirect learning control algorithms, and studies the use of such controllers in decentralized systems. The original motivation of the learning control field was learning in robots doing repetitive tasks such as on an assembly line. This paper starts with decentralized discrete time systems, and progresses to the robot application, modeling the robot as a time varying linear system in the neighborhood of the nominal trajectory, and using the usual robot controllers that are decentralized, treating each link as if it is independent of any coupling with other links. The basic result of the paper is to show that stability of the indirect learning controllers for all subsystems when the coupling between subsystems is turned off, assures convergence to zero tracking error of the decentralized indirect learning control of the coupled system, provided that the sample time in the digital learning controller is sufficiently short.

  2. Survivability via Control Objectives

    SciTech Connect

    CAMPBELL,PHILIP L.

    2000-08-11

    Control objectives open an additional front in the survivability battle. A given set of control objectives is valuable if it represents good practices, it is complete (it covers all the necessary areas), and it is auditable. CobiT and BS 7799 are two examples of control objective sets.

  3. Birth Control Explorer

    MedlinePlus

    ... Relationships STIs Media Facebook Twitter Tumblr Shares · 5 Birth Control Explorer Sort by all methods most effective methods ... MORE You are here Home » Birth Control Explorer Birth Control Explorer If you’re having sex —or if ...

  4. Birth Control Pill

    MedlinePlus

    ... 1 • 2 • 3 For Teens For Kids For Parents MORE ON THIS TOPIC About Birth Control Birth Control Methods: How Well Do They Work? ... You Need a Pelvic Exam to Get Birth Control? How Can I Get on the Pill Without Telling My Parents? How Can I Get the Pill if I ...

  5. Spacecraft nonlinear control

    NASA Technical Reports Server (NTRS)

    Sheen, Jyh-Jong; Bishop, Robert H.

    1992-01-01

    The feedback linearization technique is applied to the problem of spacecraft attitude control and momentum management with control moment gyros (CMGs). The feedback linearization consists of a coordinate transformation, which transforms the system to a companion form, and a nonlinear feedback control law to cancel the nonlinear dynamics resulting in a linear equivalent model. Pole placement techniques are then used to place the closed-loop poles. The coordinate transformation proposed here evolves from three output functions of relative degree four, three, and two, respectively. The nonlinear feedback control law is presented. Stability in a neighborhood of a controllable torque equilibrium attitude (TEA) is guaranteed and this fact is demonstrated by the simulation results. An investigation of the nonlinear control law shows that singularities exist in the state space outside the neighborhood of the controllable TEA. The nonlinear control law is simplified by a standard linearization technique and it is shown that the linearized nonlinear controller provides a natural way to select control gains for the multiple-input, multiple-output system. Simulation results using the linearized nonlinear controller show good performance relative to the nonlinear controller in the neighborhood of the TEA.

  6. Reflective Database Access Control

    ERIC Educational Resources Information Center

    Olson, Lars E.

    2009-01-01

    "Reflective Database Access Control" (RDBAC) is a model in which a database privilege is expressed as a database query itself, rather than as a static privilege contained in an access control list. RDBAC aids the management of database access controls by improving the expressiveness of policies. However, such policies introduce new interactions…

  7. Indirect decentralized repetitive control

    NASA Technical Reports Server (NTRS)

    Lee, Soo Cheol; Longman, Richard W.

    1993-01-01

    Learning control refers to controllers that learn to improve their performance at executing a given task, based on experience performing this specific task. In a previous work, the authors presented a theory of indirect decentralized learning control based on use of indirect adaptive control concepts employing simultaneous identification and control. This paper extends these results to apply to the indirect repetitive control problem in which a periodic (i.e., repetitive) command is given to a control system. Decentralized indirect repetitive control algorithms are presented that have guaranteed convergence to zero tracking error under very general conditions. The original motivation of the repetitive control and learning control fields was learning in robots doing repetitive tasks such as on an assembly line. This paper starts with decentralized discrete time systems, and progresses to the robot application, modeling the robot as a time varying linear system in the neighborhood of the desired trajectory. Decentralized repetitive control is natural for this application because the feedback control for link rotations is normally implemented in a decentralized manner, treating each link as if it is independent of the other links.

  8. CAS. Controlled Access Security

    SciTech Connect

    Martinez, B.; Pomeroy, G.

    1989-12-01

    The Security Alarm System is a data acquisition and control system which collects data from intrusion sensors and displays the information in a real-time environment for operators. The Access Control System monitors and controls the movement of personnel with the use of card readers and biometrics hand readers.

  9. Automated Serials Control System.

    ERIC Educational Resources Information Center

    Pan, Elizabeth

    In 1967, the New York State Library at Albany (NYSL) developed a tape-oriented, off-line serials control system for 10,000 active titles. The system would perform all the serials control functions: bibliographic control, check-in of current receipts, claiming for gaps in receipts and late issues, binding notification for completed sets,…

  10. Feedback control of sound

    NASA Astrophysics Data System (ADS)

    Rafaely, Boaz

    This thesis is concerned with the development an application of feedback control techniques for active sound control. Both fixed and adaptive controllers are considered. The controller design problem for active sound control is formulated as a constrained optimisation problem with an H2 performance objective, of minimising the variance of the control error, and H2 and H∞ design constraints involving control power output, disturbance enhancement, and robust stability. An Internal Model Controller with an FIR control filter is assumed. Conventional H2 design methods for feedback controllers are studied first. Although such controllers can satisfy the design constraints by employing effort terms in the quadratic cost function, they do not achieve the best possible performance, and when adapted using LMS-based algorithms, they suffer from instabilities if the plant response varies significantly. Improved H2/H∞ design methods for fixed and adaptive controllers are then developed, which achieve the best H2 performance under the design constraints, offer an improved stability when made adaptive, and in general outperform the conventional H2 controllers. The H2/H∞ design problems employ convex programming to ensure a unique solution. The Sequential Quadratic Programming methods is used for the off-line design of fixed controllers, and penalty and barrier function methods, together with frequency domain LMS-based algorithms are employed in the H2/H∞ adaptive controllers. The controllers studied and developed here were applied to three active sound control systems: a noise-reducing headset, an active headrest, and a sound radiating panel. The emphasis was put on developing control strategies that improve system performance. First, a high performance controller for the noise-reducing headset was implemented in real-time, which combines analogue and adaptive digital controllers, and can thus reject disturbances which has both broad-band and periodic components. Then

  11. Arbitrating Control of Control and Display Units

    NASA Technical Reports Server (NTRS)

    Sugden, Paul C.

    2007-01-01

    The ARINC 739 Switch is a computer program that arbitrates control of two multi-function control and display units (MCDUs) between (1) a commercial flight-management computer (FMC) and (2) NASA software used in research on transport aircraft. (MCDUs are the primary interfaces between pilots and FMCs on many commercial aircraft.) This program was recently redesigned into a software library that can be embedded in research application programs. As part of the redesign, this software was combined with software for creating custom pages of information to be displayed on a CDU. This software commands independent switching of the left (pilot s) and right (copilot s) MCDUs. For example, a custom CDU page can control the left CDU while the FMC controls the right CDU. The software uses menu keys to switch control of the CDU between the FMC or a custom CDU page. The software provides an interface that enables custom CDU pages to insert keystrokes into the FMC s CDU input interface. This feature allows the custom CDU pages to manipulate the FMC as if it were a pilot.

  12. Controls Considerations for Turbine Active Clearance Control

    NASA Technical Reports Server (NTRS)

    Melcher, Kevin J.

    2004-01-01

    This presentation discusses active control of turbine tip clearance from a control systems perspective. It is a subset of charts that were presented at the 2003 meeting of the International Society of Air Breathing Engines which was held August 31 through September 5 in Cleveland, Ohio. The associated reference paper is cited at the end of the presentation. The presentation describes active tip clearance control research being conducted by NASA to improve turbine engine systems. The target application for this effort is commercial aircraft engines. However, it is believed that the technologies developed as part of this research will benefit a broad spectrum of current and future turbomachinery. The first part of the presentation discusses the concept of tip clearance, problems associated with it, and the benefits of controlling it. It lays out a framework for implementing tip clearance controls that enables the implementation to progress from purely analytical to hardware-in-the-loop to fully experimental. And it briefly discusses how the technologies developed will be married to the previously described ACC Test Rig for hardware-in-the-loop demonstrations. The final portion of the presentation, describes one of the key technologies in some detail by presenting equations and results for a functional dynamic model of the tip clearance phenomena. As shown, the model exhibits many of the clearance dynamics found in commercial gas turbine engines. However, initial attempts to validate the model identified limitations that are being addressed to make the model more realistic.

  13. STOVL Control Integration Program

    NASA Technical Reports Server (NTRS)

    Weiss, C.; Mcdowell, P.; Watts, S.

    1994-01-01

    An integrated flight/propulsion control for an advanced vector thrust supersonic STOVL aircraft, was developed by Pratt & Whitney and McDonnell Douglas Aerospace East. The IFPC design was based upon the partitioning of the global requirements into flight control and propulsion control requirements. To validate the design, aircraft and engine models were also developed for use on a NASA Ames piloted simulator. Different flight control implementations, evaluated for their handling qualities, are documented in the report along with the propulsion control, engine model, and aircraft model.

  14. Water heater control module

    DOEpatents

    Hammerstrom, Donald J

    2013-11-26

    An advanced electric water heater control system that interfaces with a high temperature cut-off thermostat and an upper regulating thermostat. The system includes a control module that is electrically connected to the high-temperature cut-off thermostat and the upper regulating thermostat. The control module includes a switch to open or close the high-temperature cut-off thermostat and the upper regulating thermostat. The control module further includes circuitry configured to control said switch in response to a signal selected from the group of an autonomous signal, a communicated signal, and combinations thereof.

  15. CONTROL FOR NEUTRONIC REACTOR

    DOEpatents

    Lichtenberger, H.V.; Cameron, R.A.

    1959-03-31

    S>A control rod operating device in a nuclear reactor of the type in which the control rod is gradually withdrawn from the reactor to a position desired during stable operation is described. The apparatus is comprised essentially of a stop member movable in the direction of withdrawal of the control rod, a follower on the control rod engageable with the stop and means urging the follower against the stop in the direction of withdrawal. A means responsive to disengagement of the follower from the stop is provided for actuating the control rod to return to the reactor shut-down position.

  16. Intelligent flight control systems

    NASA Technical Reports Server (NTRS)

    Stengel, Robert F.

    1993-01-01

    The capabilities of flight control systems can be enhanced by designing them to emulate functions of natural intelligence. Intelligent control functions fall in three categories. Declarative actions involve decision-making, providing models for system monitoring, goal planning, and system/scenario identification. Procedural actions concern skilled behavior and have parallels in guidance, navigation, and adaptation. Reflexive actions are spontaneous, inner-loop responses for control and estimation. Intelligent flight control systems learn knowledge of the aircraft and its mission and adapt to changes in the flight environment. Cognitive models form an efficient basis for integrating 'outer-loop/inner-loop' control functions and for developing robust parallel-processing algorithms.

  17. Controls and guidance research

    NASA Technical Reports Server (NTRS)

    Homaifar, Abdollah; Dunn, Derome; Song, Yong-Duan; Lai, Steven H.-Y.

    1992-01-01

    The objectives of the control group are concentrated on research and education. The control problem of the hypersonic space vehicle represents an important and challenging issue in aerospace engineering. The work described in this report is part of our effort in developing advanced control strategies for such a system. In order to achieve the objectives stated in the NASA-CORE proposal, the tasks were divided among the group based upon their educational expertise. Within the educational component we are offering a Linear Systems and Control course for students in electrical and mechanical engineering. Also, we are proposing a new course in Digital Control Systems with a corresponding laboratory.

  18. Conscious Control over Action

    PubMed Central

    Shepherd, Joshua

    2015-01-01

    The extensive involvement of nonconscious processes in human behaviour has led some to suggest that consciousness is much less important for the control of action than we might think. In this article I push against this trend, developing an understanding of conscious control that is sensitive to our best models of overt (that is, bodily) action control. Further, I assess the cogency of various zombie challenges—challenges that seek to demote the importance of conscious control for human agency. I argue that though nonconscious contributions to action control are evidently robust, these challenges are overblown. PMID:26113753

  19. Recursive Deadbeat Controller Design

    NASA Technical Reports Server (NTRS)

    Juang, Jer-Nan; Phan, Minh Q.

    1997-01-01

    This paper presents a recursive algorithm for a deadbeat predictive controller design. The method combines together the concepts of system identification and deadbeat controller designs. It starts with the multi-step output prediction equation and derives the control force in terms of past input and output time histories. The formulation thus derived satisfies simultaneously system identification and deadbeat controller design requirements. As soon as the coefficient matrices are identified satisfying the output prediction equation, no further work is required to compute the deadbeat control gain matrices. The method can be implemented recursively just as any typical recursive system identification techniques.

  20. PDX operating controls

    SciTech Connect

    Mathe, P.; Robertson, R.; Woolley, R.D.

    1981-01-01

    The Poloidal Divertor experiment began operation in November 1978. Some of the operating controls were in working condition a year before that date for power tests. In fact, a very similar system to the one used for PDX operated the FM-1 experiment as early as 1971. The functional block diagram of the PDX operating controls is shown. The operating console provides the man-machine interface during the experiment. Most status lights and pushbotton controls are directly interfaced to the IBM 1800 computer. This computer in conjunction with an IPC-300 programmable controller and a CAMAC serial highway system, performs the supervisory and control functions associated with the various PDX subsystems.

  1. Control and optimization system

    DOEpatents

    Xinsheng, Lou

    2013-02-12

    A system for optimizing a power plant includes a chemical loop having an input for receiving an input parameter (270) and an output for outputting an output parameter (280), a control system operably connected to the chemical loop and having a multiple controller part (230) comprising a model-free controller. The control system receives the output parameter (280), optimizes the input parameter (270) based on the received output parameter (280), and outputs an optimized input parameter (270) to the input of the chemical loop to control a process of the chemical loop in an optimized manner.

  2. Decentralized adaptive control

    NASA Technical Reports Server (NTRS)

    Oh, B. J.; Jamshidi, M.; Seraji, H.

    1988-01-01

    A decentralized adaptive control is proposed to stabilize and track the nonlinear, interconnected subsystems with unknown parameters. The adaptation of the controller gain is derived by using model reference adaptive control theory based on Lyapunov's direct method. The adaptive gains consist of sigma, proportional, and integral combination of the measured and reference values of the corresponding subsystem. The proposed control is applied to the joint control of a two-link robot manipulator, and the performance in computer simulation corresponds with what is expected in theoretical development.

  3. SPS antenna pointing control

    NASA Technical Reports Server (NTRS)

    Hung, J. C.

    1980-01-01

    The pointing control of a microwave antenna of the Satellite Power System was investigated emphasizing: (1) the SPS antenna pointing error sensing method; (2) a rigid body pointing control design; and (3) approaches for modeling the flexible body characteristics of the solar collector. Accuracy requirements for the antenna pointing control consist of a mechanical pointing control accuracy of three arc-minutes and an electronic phased array pointing accuracy of three arc-seconds. Results based on the factors considered in current analysis, show that the three arc-minute overall pointing control accuracy can be achieved in practice.

  4. Intelligent Control Systems Research

    NASA Technical Reports Server (NTRS)

    Loparo, Kenneth A.

    1994-01-01

    Results of a three phase research program into intelligent control systems are presented. The first phase looked at implementing the lowest or direct level of a hierarchical control scheme using a reinforcement learning approach assuming no a priori information about the system under control. The second phase involved the design of an adaptive/optimizing level of the hierarchy and its interaction with the direct control level. The third and final phase of the research was aimed at combining the results of the previous phases with some a priori information about the controlled system.

  5. Modeling and control of thermostatically controlled loads

    SciTech Connect

    Backhaus, Scott N; Sinitsyn, Nikolai; Kundu, S.; Hiskens, I.

    2011-01-04

    As the penetration of intermittent energy sources grows substantially, loads will be required to play an increasingly important role in compensating the fast time-scale fluctuations in generated power. Recent numerical modeling of thermostatically controlled loads (TCLs) has demonstrated that such load following is feasible, but analytical models that satisfactorily quantify the aggregate power consumption of a group of TCLs are desired to enable controller design. We develop such a model for the aggregate power response of a homogeneous population of TCLs to uniform variation of all TCL setpoints. A linearized model of the response is derived, and a linear quadratic regulator (LQR) has been designed. Using the TCL setpoint as the control input, the LQR enables aggregate power to track reference signals that exhibit step, ramp and sinusoidal variations. Although much of the work assumes a homogeneous population of TCLs with deterministic dynamics, we also propose a method for probing the dynamics of systems where load characteristics are not well known.

  6. Integrated Biological Control

    SciTech Connect

    JOHNSON, A.R.

    2003-10-09

    Biological control is any activity taken to prevent, limit, clean up, or remediate potential environmental, health and safety, or workplace quality impacts from plants, animals, or microorganisms. At Hanford the principal emphasis of biological control is to prevent the transport of radioactive contamination by biological vectors (plants, animals, or microorganisms), and where necessary, control and clean up resulting contamination. Other aspects of biological control at Hanford include industrial weed control (e.g.; tumbleweeds), noxious weed control (invasive, non-native plant species), and pest control (undesirable animals such as rodents and stinging insects, and microorganisms such as molds that adversely affect the quality of the workplace environment). Biological control activities may be either preventive (a priori) or in response to existing contamination spread (a posteriori). Surveillance activities, including ground, vegetation, flying insect, and other surveys, and a priori control actions, such as herbicide spraying and placing biological barriers, are important in preventing radioactive contamination spread. If surveillance discovers that biological vectors have spread radioactive contamination, a posteriori control measures, such as fixing contamination, followed by cleanup and removal of the contamination to an approved disposal location are typical response functions. In some cases remediation following the contamination cleanup and removal is necessary. Biological control activities for industrial weeds, noxious weeds and pests have similar modes of prevention and response.

  7. Integrated Biological Control

    SciTech Connect

    JOHNSON, A.R.

    2002-09-01

    Biological control is any activity taken to prevent, limit, clean up, or remediate potential environmental, health and safety, or workplace quality impacts from plants, animals, or microorganisms. At Hanford the principal emphasis of biological control is to prevent the transport of radioactive contamination by biological vectors (plants, animals, or microorganisms), and where necessary, control and clean up resulting contamination. Other aspects of biological control at Hanford include industrial weed control (e.g.; tumbleweeds), noxious weed control (invasive, non-native plant species), and pest control (undesirable animals such as rodents and stinging insects; and microorganisms such as molds that adversely affect the quality of the workplace environment). Biological control activities may be either preventive (apriori) or in response to existing contamination spread (aposteriori). Surveillance activities, including ground, vegetation, flying insect, and other surveys, and apriori control actions, such as herbicide spraying and placing biological barriers, are important in preventing radioactive contamination spread. If surveillance discovers that biological vectors have spread radioactive contamination, aposteriori control measures, such as fixing contamination, followed by cleanup and removal of the contamination to an approved disposal location are typical response functions. In some cases remediation following the contamination cleanup and removal is necessary. Biological control activities for industrial weeds, noxious weeds and pests have similar modes of prevention and response.

  8. CRUCIFORM CONTROL ROD JOINT

    DOEpatents

    Thorp, A.G. II

    1962-08-01

    An invention is described which relates to nuclear reactor control rod components and more particularly to a joint between cruciform control rod members and cruciform control rod follower members. In one embodiment this invention provides interfitting crossed arms at adjacent ends of a control rod and its follower in abutting relation. This holds the members against relative opposite longitudinal movement while a compression member keys the arms against relative opposite rotation around a common axis. Means are also provided for centering the control rod and its follower on a common axis and for selectively releasing the control rod from its follower for the insertion of a replacement of the control rod and reuse of the follower. (AEC)

  9. Controlling chaos faster

    SciTech Connect

    Bick, Christian; Kolodziejski, Christoph; Timme, Marc

    2014-09-01

    Predictive feedback control is an easy-to-implement method to stabilize unknown unstable periodic orbits in chaotic dynamical systems. Predictive feedback control is severely limited because asymptotic convergence speed decreases with stronger instabilities which in turn are typical for larger target periods, rendering it harder to effectively stabilize periodic orbits of large period. Here, we study stalled chaos control, where the application of control is stalled to make use of the chaotic, uncontrolled dynamics, and introduce an adaptation paradigm to overcome this limitation and speed up convergence. This modified control scheme is not only capable of stabilizing more periodic orbits than the original predictive feedback control but also speeds up convergence for typical chaotic maps, as illustrated in both theory and application. The proposed adaptation scheme provides a way to tune parameters online, yielding a broadly applicable, fast chaos control that converges reliably, even for periodic orbits of large period.

  10. Controllability of complex networks.

    PubMed

    Liu, Yang-Yu; Slotine, Jean-Jacques; Barabási, Albert-László

    2011-05-12

    The ultimate proof of our understanding of natural or technological systems is reflected in our ability to control them. Although control theory offers mathematical tools for steering engineered and natural systems towards a desired state, a framework to control complex self-organized systems is lacking. Here we develop analytical tools to study the controllability of an arbitrary complex directed network, identifying the set of driver nodes with time-dependent control that can guide the system's entire dynamics. We apply these tools to several real networks, finding that the number of driver nodes is determined mainly by the network's degree distribution. We show that sparse inhomogeneous networks, which emerge in many real complex systems, are the most difficult to control, but that dense and homogeneous networks can be controlled using a few driver nodes. Counterintuitively, we find that in both model and real systems the driver nodes tend to avoid the high-degree nodes.

  11. Jet control carburetor

    SciTech Connect

    Fujikake, K.; Idota, Y.; Ohsawa, K.; Sugiyama, K.

    1982-06-29

    A jet control type carburetor according to the present invention includes an intake pipe having an intake passage formed in an inner wall thereof, the intake passage allowing an intake air to flow therethrough; a venturi provided in the intake pipe, for controlling flow velocity and pressure of the intake air in the intake passage; a fuel nozzle opened into the intake passage and connected to a fuel supply source through a fuel passage for sucking the fuel within the intake passage from the fuel nozzle in order to introduce the mixture of air and fuel within the intake passage; a throttle valve provided downstream of the venturi, for controlling the flow rate of the mixture of intake air and fuel; a control air nozzle opened into the intake passage and connected to an air supply source through a control air passage for jetting the flow of the control air to the fuel spurted from the fuel nozzle to afford the kinetic energy of the control air to the fuel; and a throttle means provided upstream of the control air nozzle in the control air passage, for controlling the flow rate of the control air. The control air nozzle has a predetermined inner diameter (da) and is provided at a portion apart from the fuel nozzle with a predetermined spacing (w), and a dimensional relationship of the spacing W between the fuel nozzle and the control air nozzle to the inner diameter (da) of the control air nozzle is set as follows: w/da < or = 20.

  12. MULTIPLE OSCILLATION STABILIZING CONTROL.

    SciTech Connect

    YUE,M.; SCHLUETER,R.; AZARM,M.; BARI,R.

    2004-07-23

    This paper presents a strategy that may be used to guide stabilizing control design for multiple oscillations, which are difficult to control using conventional control design procedures. A multiple oscillation phenomena is observed in an example power system. A local bifurcation and an interarea bifurcation develop in an example power system due to multiple bifurcation parameter variations. The dynamic behaviors of the bifurcating system are complex due to the overlapping of the two different bifurcation subsystems and are shown to be difficult to control. The double bifurcations are studied in this paper and in order to stabilize them, three kind of {mu}-synthesis robust controls are designed, (a) {mu}-synthesis power system stabilizer (MPSS); (b) {mu}-synthesis SVC control (MSVC); and (c) a mixed MPSS/MSVC control. Based on the bifurcation subsystem analysis, the measurement signals and locations of the controls are selected. The control performances of three kind of controls are evaluated and compared. The conclusions are given according to the analysis and time simulation results.

  13. [Controlling in clinical management].

    PubMed

    Bähr, K; Ellinger, K

    1999-02-01

    Managers of industrial enterprises strive continually to improve the efficiency of production, distribution and service for their customers in order to be able to compete on the market. In socially orientated non-profit-organisations this is not universe practice. Relating to section 17 Abs. 1 KHG and section 13 BPfIV of German social legislation hospital charges are refunded only, if the hospital is working efficiently and economically. Controlling is a tool to achieve these goals. Controlling coordinates the flow of information for planning and evaluation. Strategic and operative controlling are closely interrelated: Strategic controlling is directed towards new and promising activities, operative controlling supports decision--making--including future-oriented aspects-by providing and condensing information. Controlling is definitely not intended to dictate or "command" any action. Its object is to serve as an instrument or tool supporting result-oriented planning, regulating and evaluation.

  14. Flight control actuation system

    NASA Technical Reports Server (NTRS)

    Wingett, Paul T. (Inventor); Gaines, Louie T. (Inventor); Evans, Paul S. (Inventor); Kern, James I. (Inventor)

    2004-01-01

    A flight control actuation system comprises a controller, electromechanical actuator and a pneumatic actuator. During normal operation, only the electromechanical actuator is needed to operate a flight control surface. When the electromechanical actuator load level exceeds 40 amps positive, the controller activates the pneumatic actuator to offset electromechanical actuator loads to assist the manipulation of flight control surfaces. The assistance from the pneumatic load assist actuator enables the use of an electromechanical actuator that is smaller in size and mass, requires less power, needs less cooling processes, achieves high output forces and adapts to electrical current variations. The flight control actuation system is adapted for aircraft, spacecraft, missiles, and other flight vehicles, especially flight vehicles that are large in size and travel at high velocities.

  15. Chimpanzee Cognitive Control

    PubMed Central

    Beran, Michael J.

    2015-01-01

    Cognitive control processes are a feature of human cognition. Recent comparative tests have shown that some nonhuman animals also might share aspects of cognitive control with humans. Two of the executive processes that constitute cognitive control are metacognition and self-control, and recent experiments with chimpanzees are described that demonstrate metacognitive monitoring and control when these animals engage in an information-seeking task. Chimpanzees also show strategic responding in a self-control task by exhibiting self-distraction as an aid to delay of gratification. These demonstrations indicate continuity with similar human cognitive capacities, and the performances of chimpanzees in these kinds of tests have implications for considering the nature of the intelligence of these animals. PMID:26478660

  16. Nuclear reactor control

    DOEpatents

    Cawley, William E.; Warnick, Robert F.

    1982-01-01

    1. In a nuclear reactor incorporating a plurality of columns of tubular fuel elements disposed in horizontal tubes in a mass of graphite wherein water flows through the tubes to cool the fuel elements, the improvement comprising at least one control column disposed in a horizontal tube including fewer fuel elements than in a normal column of fuel elements and tubular control elements disposed at both ends of said control column, and means for varying the horizontal displacement of the control column comprising a winch at the upstream end of the control column and a cable extending through the fuel and control elements and attached to the element at the downstream end of the column.

  17. Flight control actuation system

    NASA Technical Reports Server (NTRS)

    Wingett, Paul T. (Inventor); Gaines, Louie T. (Inventor); Evans, Paul S. (Inventor); Kern, James I. (Inventor)

    2006-01-01

    A flight control actuation system comprises a controller, electromechanical actuator and a pneumatic actuator. During normal operation, only the electromechanical actuator is needed to operate a flight control surface. When the electromechanical actuator load level exceeds 40 amps positive, the controller activates the pneumatic actuator to offset electromechanical actuator loads to assist the manipulation of flight control surfaces. The assistance from the pneumatic load assist actuator enables the use of an electromechanical actuator that is smaller in size and mass, requires less power, needs less cooling processes, achieves high output forces and adapts to electrical current variations. The flight control actuation system is adapted for aircraft, spacecraft, missiles, and other flight vehicles, especially flight vehicles that are large in size and travel at high velocities.

  18. Unpacking Self-Control

    PubMed Central

    Duckworth, Angela; Steinberg, Laurence

    2014-01-01

    Self-controlled behavior refers to actions aligned with valued, longer-term goals in the face of conflicting impulses to seek immediate gratification. In this article, we argue that the psychological processes that contribute to self-controlled behavior can be grouped into two functionally distinct categories: Volitional processes facilitate self-controlled behavior and include executive functions as well as learned metacognitive strategies like planning, attention deployment, and psychological distancing. In contrast, impulsigenic processes undermine self-controlled behavior and include reward sensitivity, sensation seeking, and domain-specific cravings. A disproportionate amount of research has addressed the former at the expense of understanding individual and developmental differences in the latter. This imbalance is now being rectified. Distinguishing between self-controlled behavior and its antecedent psychological processes helps illuminate normative developmental changes in self-control and points to directions for measurement and intervention. PMID:25821515

  19. Advanced Aerodynamic Control Effectors

    NASA Technical Reports Server (NTRS)

    Wood, Richard M.; Bauer, Steven X. S.

    1999-01-01

    A 1990 research program that focused on the development of advanced aerodynamic control effectors (AACE) for military aircraft has been reviewed and summarized. Data are presented for advanced planform, flow control, and surface contouring technologies. The data show significant increases in lift, reductions in drag, and increased control power, compared to typical aerodynamic designs. The results presented also highlighted the importance of planform selection in the design of a control effector suite. Planform data showed that dramatic increases in lift (greater than 25%) can be achieved with multiple wings and a sawtooth forebody. Passive porosity and micro drag generator control effector data showed control power levels exceeding that available from typical effectors (moving surfaces). Application of an advanced planform to a tailless concept showed benefits of similar magnitude as those observed in the generic studies.

  20. Fuzzy logic controller optimization

    DOEpatents

    Sepe, Jr., Raymond B; Miller, John Michael

    2004-03-23

    A method is provided for optimizing a rotating induction machine system fuzzy logic controller. The fuzzy logic controller has at least one input and at least one output. Each input accepts a machine system operating parameter. Each output produces at least one machine system control parameter. The fuzzy logic controller generates each output based on at least one input and on fuzzy logic decision parameters. Optimization begins by obtaining a set of data relating each control parameter to at least one operating parameter for each machine operating region. A model is constructed for each machine operating region based on the machine operating region data obtained. The fuzzy logic controller is simulated with at least one created model in a feedback loop from a fuzzy logic output to a fuzzy logic input. Fuzzy logic decision parameters are optimized based on the simulation.