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Sample records for misonidazole metronidazole mice

  1. Relationship between misonidazole toxicity and core temperature in C3H mice

    International Nuclear Information System (INIS)

    Gomer, C.J.; Johnson, R.J.

    1979-01-01

    A single intraperitoneal injection of the radiation sensitizer misonidazole at doses greater than 0.5 mg/g was found to produce a transient hypothermic response in C3H mice. An increase in the acute toxicity of this drug was demonstrated when the animal core temperature was maintained at a normal 35 to 37 0 C by placing the mice in a warmed environment immediately following injection of the drug. The LD/sub 50/3 days/ dose of misonidazole was determined to be 1.48 mg/g for mice allowed to become hypothermic following injection but 0.77 mg/g for mice maintained at a normal core temperature following injection

  2. Metabolism and pharmacokinetics of the hypoxic cell radiosensitizer and cytotoxic agent, misonidazole, in C3H mice

    International Nuclear Information System (INIS)

    Chin, J.B.; Rauth, A.M.

    1981-01-01

    Misonidazole, a 2-nitroimidazole, is presently of interest because of its radiosensitizing and toxic effects toward hypoxic tumor cells. The plasma and tissue distribution of misonidazole and various products was studied as a function of time and mode of administration in male C3H mice with KHT tumors. Polarographic measurements of nitro-group species in plasma after intravenous or intraperitoneal misonidazole administration indicated apparent half-lives of 1.0 to 1.5 hr. With an oral dose, a multicomponent curve was obtained. [ 14 C]misonidazole, labeled in the 2-position of the imidazole ring, was widely distributed to all tissues tested after intraperitioneal or oral administration. Paper chromatography of plasma and the water-soluble fraction of spleen, liver, kidney, brain, and KHT tumor tissue showed variations in the proportions of misonidazole, its 0-dimethylation product, the aminoimidazole, and low-R/sub F/ products (including glucuronides). There was radioactivity in the gastrointestinal lumen 1 hr after intravenous injection. These studies indicate that differences exist in total drug levels as well as in the proportions of metabolites present in various tissue types. Thus the radiosensitization and toxicity of misonidazole may depend on the particular tissue or tumor under study

  3. Effect of combined misonidazole and accelerated neon ions on a human melanoma transplanted into nude mice

    International Nuclear Information System (INIS)

    Guichard, M.; Tenforde, T.; Curtis, S.; Malaise, E.P.

    1982-01-01

    The response to accelerated neon ions of human Nall melanomas growing in nude mice was measured by an in vitro colony-forming assay following in situ tumor irradiation in the midposition of a 10-cm extended-peak ionization region. Values of the relative biological effectiveness (RBE) for peak neon ions compared with 60 Coγ radiation were 3.2 and 3.4, respectively, at the 1% and 10% survival levels. Following irradiation with peak neon ions, the repair of potentially lethal damage (PLD) was comparable to that observed after γ irradiation. When misonidazole (1 mg/g intraperitoneal dose) was administered in combination with extended-peak neon ions, the drug enhancement ratio (ER) at the 1% survival level was 1.5 if the tumors were removed and plated in vitro immediately following irradiation, and 1.9 if tumor excision and plating were delayed for greater than or equal to 6 hours. Administration of misonidazole completely inhibited PLD repair following either γ irradiation or extended peak neon-ion irradiation

  4. Distribution and tumour cytotoxicity of the radiosensitizer misonidazole (Ro-07-0582) in C57 mice

    International Nuclear Information System (INIS)

    Pedersen, J.E.; Smith, M.R.; Bugden, R.D.; Peckham, M.J.

    1979-01-01

    The distribution and clearance of misonidazole (MIS=Ro-07-0582) were studied in C57 mouse tissued and in transplants of Lewis lung tumour. The half life of the drug in blood after a dose of 1mg/g i.p. was 3 h. Some tissues, such as liver, were found to have consistently low MIS levels, and this was found to be due to degradation of the drug after removal of the tissues from the host. The in vivo cytotoxicity of MIS to Lewis lung tumour cells was studied using an in-vitro colony assay. After half of the tumours had been irradiated with 10 Gy to kill most of the oxic cells, the mice received i.p. injections of MIS. To simulate the longer drug exposure of human tumour cells (due to the longer half life in man) a repeated injection regime was used in some mice. There was no significant cell kill after a single dose, but with a prolonged exposure to the drug in the multiply injected animals, cell survival was reduced to 50% of control in both the irradiated and unirradiated tumours. Since the hypoxic fraction of the unirradiated tumour is probably not more than 30%, it would appear that MIS is not selectively cytotoxic to hypoxic cells. However, MIS had a much greater cytotoxic effect upon hypoxic Lewis lung tumour cells in vitro, with very little or no effect on cells grown in air. This would support the theory that the presence of hypoxic cells is essential for the expression of MIS cytotoxicity. (author)

  5. The influence of metronidazole on free thymidine content of blood serum of irradiated mice

    International Nuclear Information System (INIS)

    Konov, A.V.; Ryabchenko, N.I.

    1986-01-01

    The influence of a radiosensitizer, metronidazole, on the free thymidine content of blood serum of irradiated mice was studied in aerobic and hypoxic conditions. A heated metronidazole solution (1 mg/g) was administered intraperitoneally 30 min before irradiation of animals with a dose of 3 Gy. Thymidine concentration in blood serum was determined by the radioimmunological technique. The influence of metronidazole on the level of thymidinemia was only noted in the animals exposed under hypoxic conditions

  6. Plasma concentrations of misonidazole

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    Notter, G; Rylander, U; Turesson, I

    1980-10-01

    The plasma concentrations of misonidazole doses between 0.6 and 2.0 g/m/sup 2/ were analyzed in respect to the variation within the same patient and between different patients. Peak plasma levels were observed after 2 hours. The mean plasma levels of misonidazole only at 3 hours were 23.8, 47.0 and 76.5 ..mu..g/ml after misonidazole doses of 0.6, 1.2 g/m/sup 2/, respectively. The half-life of misonidazole only was found to be 8.2 hours for women and 10.5 for men. Good linearity between plasma levels and drug doses was observed after administration of different single doses to the same patient within the dose range 0.6 to 2.0 g/m/sup 2/.

  7. Treatment of Clostridium difficile infection in mice with vancomycin alone is as effective as treatment with vancomycin and metronidazole in combination

    DEFF Research Database (Denmark)

    Erikstrup, Lise Tornvig; Aarup, Mie; Hagemann-Madsen, Rikke

    2015-01-01

    OBJECTIVE: Clostridium difficile is a major cause of nosocomial infectious diarrhoea. Treatment of C. difficile infection (CDI) depends on disease severity. A combination of vancomycin and metronidazole is often recommended in severe cases. The aim of this study was to examine, in a murine model....... difficile toxins. RESULTS: None of the mice in the vancomycin-treated group died during the treatment phase compared to a mortality of 17%, 33% and 55% in the combination, metronidazole and infected control group, respectively. Mice treated with vancomycin alone or in combination with metronidazole...... of CDI, if mice treated with a combination of vancomycin and metronidazole had a better clinical outcome than mice treated with vancomycin or metronidazole alone. DESIGN: C57BL/6J mice pretreated with an antimicrobial mixture were challenged with C. difficile VPI 10463 or phosphate-buffered saline...

  8. Enhancement of misonidazole radiosensitization by an inhibitor of glutathione biosynthesis

    International Nuclear Information System (INIS)

    Hodgkiss, R.J.; Middleton, R.W.

    1983-01-01

    A well known inhibitor of glutathione biosynthesis, buthione sulphoximine (S-n-butyl homocysteine sulphoximine, BSO) depletes non-protein sulphydryls (NPSH) in Chinese hamster cells in vitro, resulting in a marked increase in the radiosensitization efficiency of misonidazole. V79 379A Chinese hamster cells were maintained in suspension cultures and irradiated in monolayers using 250 kVp X-rays at a dose rate of 3.93 Gy/min. Radiosensitization by misonidazole alone gave results within 0.1 sensitizer enhancement ratio (s.e.r.) of the curve reported by Watts et al. (1980). GSH (2 mmol dm - 3 ) added to the extracellular medium resulted in a marked decrease in the radiosensitization efficiency of misonidazole, eliminating the effect at 0.1 mmol dm - 3 misonidazole (s.e.r. = 1.0 relative to nitrogen control). A marked enhancement of the radiosensitization by misonidazole was observed when the cells had been incubated with BSO (0.1 mmol dm - 3 ). BSO alone at this concentration gave s.e.r. = 1.17; misonidazole alone (0.1 mmol dm - 3 ) gave s.e.r. = 1.18 and misonidazole with BSO (both 0.1. mmol dm - 3 ) gave s.e.r. = 1.9. The BSO treatment gave little effect in aerated cells. The concentration of BSO needed to produce these effects in vitro is ca. 40-fold lower than doses tolerated by mice in repeated administrations. (U.K.)

  9. Effect of misonidazole on radiosensitivity of Ehrlich ascites tumor cells

    International Nuclear Information System (INIS)

    Takeuchi, Hiroshi

    1986-01-01

    The effect of Misonidazole on radiosensitivity of Ehrlich ascites tumor cells was studied in vivo. Ehrlich ascites tumor cells growing intraperitoneally (ICR/SIC mice) for either 1, 4, 6 or 10 days were irradiated in vivo (whole body irradiation) with or without Misonidazole. Immediately after irradiation tumor cells were transplanted intraperitoneally into new animals. Four days later, the propagated surviving cells were removed and counted for analyses. Enhancement ratio of Misonidazole at the surviving fraction of 0.1 were 1.0 (for 1-day-old), 1.3 (for 4-day-old), 1.9 (for 6-day-old), 1.9 (for 10-day-old) and 2.8 (for anoxic cells) respectively. The gradual increase of the enhancement ratio of the ascites tumore cells during intraperitoneal growth from 1 through 10 days might be attributed to an increase of hypoxic tumor cells. Cytotoxicity was not observed at 0.1 mg per gram body weight of Misonidazole but was at 1 mg per gram body weight of Misonidazole in 6-day-old and 10-day-old Ehrlich ascites tumor cells which were supposed to contain hypoxic cells. These results suggest that Misonidazole may prove an effective radiosensitizer for hypoxic tumor cells. (author)

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

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    Poonam Singh

    2013-01-01

    Full Text Available Background: Metronidazole (MTZ is commonly used as an antibacterial and antiprotozoaldrug. Various doses of MTZ have been reported to inhibit spermatogenic activityand sperm indices.Materials and Methods: In this experimental study, dose-dependent effects of MTZ onthe structural and functional integrity of the testis and accessory reproductive organshave been investigated. Adult male mice of Swiss strain were administered orally withMTZ at the doses of 250 mg/kgBW/day and 500 mg/kgBW/day for 28 consecutive daysto 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 cessationof the treatment.Results: Therapeutic dose of MTZ (250 mg/kgBW/day neither altered the weights ofthe 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 theweights of the testis and epididymis. Histoarchitecture of the testis and epididymis at thehigh dose revealed marked regressive changes while that of seminal vesicle remainedunaffected. Significant reductions were noticed in the motility, viability and count ofepididymal spermatozoa while the concentrations of epididymal sialic acid and seminalvesicular fructose remained unaltered after the treatment. No significant changes werenoticed in the mating ability as well as in the level of serum testosterone in the treatedmice. Fertility of the male mice treated with high dose of MTZ declined markedly leadingto an increase in pre- and postimplantation loss while a significant decrease wasnoticed in the number of live blastocysts in females impregnated with such males. MTZinducedchanges in the male reproductive organs and fertility were reinstated 42 daysafter cessation of the treatment.Conclusion: High dose of MTZ induced reversible deleterious effects on the male reproductionand fertility.

  11. Influence of metronidazole on the survival rate of whole-body irradiated mice and on the DNA repair synthesis of lymphocytes

    International Nuclear Information System (INIS)

    Magdon, E.; Schroeder, E.

    1978-01-01

    With reference to literature reports the effect of Metronidazole [1-(hydroxyethyl)-5-nitro-2-methyl-imidazole] on the survival rate of C 3 H inbred mice following whole-body doses ranging from 5 to 15 Gy was determined under oxic and hypoxic conditions. Ehrlich ascites tumor cells were used to study the influence of Metronidazole on radiation-induced alterations of the DNA sedimentation behavior in the alkaline sucrose gradient under oxic conditions in vitro. The effect of Metronidazole on the semiconservative DNA synthesis was investigated under oxic and hypoxic conditions in Ehrlich ascites carcinoma cells and L5178Y lymphoma cells. Furthermore, it was examined whether the radiation-induced inhibition of semiconservative DNA synthesis in L5178Y lymphoma cells and the radiation-induced repair synthesis in lymphocytes is influenced by Metronidazole. From the values of the LDsub(50/30) after whole-body irradiation a sensitilization factor of 1.3 was derived for Metronidazole under hypoxic conditions. Under atmospheric conditions an increase of the radiation effect by a factor of 1.1 was obtained. The protective factor of hypoxia was 1.6 and thus greater than the radiosensibilization caused by Metronidazole. The DNA synthesis was slightly inhibited by Metronidazole under both hypoxic and euoxic conditions. The studies revealed no significant influence of Metronidazole on radiation-induced changes of the DNA sedimentation behavior and of the DNA repair synthesis as well as on the radiation induced inhibition of semiconservative DNA synthesis. (author)

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

    Science.gov (United States)

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

    2017-03-01

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

  13. Effects of misonidazole, irradiation and hyperthermia on lysosomal enzyme activity in mouse tumours

    International Nuclear Information System (INIS)

    Barratt, G.M.; Wills, E.D.

    1981-01-01

    Male C3H mice bearing transplanted tumours were treated with hyperthermia, gamma radiation and the radiosensitising drug misonidazole. The activity of tumour lysosomal acid phosphatase and β-glucuronidase was determined using quantitative cytochemical techniques which measure both lysosomal membrane permeability and enzyme activity. Misonidazole had no effect on the membrane permeability or enzyme activity of tumour lysosomes 1 hr after injection; but 25 hr after the drug treatment the permeability of the lysosomal membrane to the substrate was increased to 1.7 times control. Increases in the lysosomal enzyme activity and membrane permeability were observed 1 hr after combined treatment with misonidazole and irradiation, although neither the drug nor irradiation given alone affected the lysosomes 1 hr after treatment. Twenty-five hours after treatment of tumours with misonidazole given 25 minutes before irradiation of tumours, permeability of the lysosomal membrane had increased to 2.3 times the control. The effects of the irradiation and the radio-sensitisers were thus synergistic. Hyperthermic treatment of tumours increased and misonidazole decreased the lysosomal membrane permeability and enzyme activity measured immediately after exposure. Thus misonidazole and irradiation act synergistically to cause increased lysosomal activity but misonidazole depresses the effect of hyperthermia on lysosomes. (author)

  14. Ameliorative effects of curcumin on the spermatozoon tail length, count, motility and testosterone serum level in metronidazole-treated mice.

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    Karbalay-Doust, S; Noorafshan, A

    2011-01-01

    Metronidazole (MTZ) is used as an antiparasitic drug. Curcumin is considered as anti-oxidant and anti-inflammatory agent. The ameliorative effects of curcumin on MTZ induced toxicity on mice spermatozoon tail length, count, motility and testosterone level were investigated. MTZ was administered in 500 and 165 (high and therapeutic doses) mg/kg/day, with and without curcumin (100 mg/kg/day). After 16 days the above parameters were assessed. Spermatozoon count and motility and serum testosterone level MTZ-treated (500 and 165) mice were reduced. In the mice treated with MTZ+curcumin these parameters decreased but in a lesser extent than the MTZ-treated animals. Mid-piece and total lengths of the spermatozoon tail in control animals were 31.6 ± 9.0 μm and 100.3 ± 15.0 μm and in the mice treated with high doses (500) of MTZ were reduced. The mid-piece and total spermatozoon tail length has been decreased in a lesser extent in the mice treated with high dose MTZ+curcumin than the mice treated with high dose MTZ (paverage increase in mid-piece and total lengths in comparison with the MTZ-treated (500) animals. Stereological estimation of the sperm tail length, including sampling of spermatozoa and also counting of the intersections of their tails with the stereological grids was a rapid technique and took only 5-10 minutes. It can be concluded that curcumin has an ameliorative effect on the spermatozoon, testosterone level and tail length in MTZ-treated mice.

  15. Misonidazole-glutathione conjugates in CHO cells

    International Nuclear Information System (INIS)

    Varghese, A.J.; Whitmore, G.F.

    1984-01-01

    Misonidazole, after reduction to the hydroxylamine derivative, reacts with glutathione (GSH) under physiological conditions. The reaction product has been identified as a mixture of two isomeric conjugates. When water soluble extracts of CHO cells exposed to misonidazole under hypoxic conditions are subjected to HPLC analysis, misonidazole derivatives, having the same chromatographic properties as the GSH-MISO conjugates, were detected. When CHO cells were incubated with misonidazole in the presence of added GSH, a substantial increase in the amount of the conjugate was detected. When extracts of CHO cells exposed to misonidazole under hypoxia were subsequently exposed to GSH, an increased formation of the conjugate was observed. A rearrangement product of the hydroxylamine derivative of misonidazole is postulated as the reactive intermediate responsible for the formation of the conjugate

  16. Metronidazole hypersensitivity.

    Science.gov (United States)

    Knowles, S; Choudhury, T; Shear, N H

    1994-03-01

    To report a case of a possible hypersensitivity reaction induced by metronidazole. An Asian woman with a history of recurrent vaginitis had previously developed localized erythema while on intravaginal metronidazole and nystatin. While receiving oral metronidazole for treatment of a current bacterial vaginosis, she developed chills, fever, generalized erythema, and a rash within 60 minutes of the first dose. Treatment with diphenhydramine was instituted. The following day while in the hospital, the patient's condition worsened; she experienced shortness of breath and increased edema of the extremities. Methylprednisolone was administered with diphenhydramine and her condition improved over the next 5 days. The patient's vaginitis was treated with gentian violet and she was discharged on a tapering dosage of prednisone. Metronidazole-induced cutaneous reactions and systemic hypersensitivity reactions are reviewed. Alternatives to metronidazole and other potential cross-reactive drugs are suggested for the treatment of recurrent vaginitis. Although the patient's initial reaction to metronidazole represented a rare event, written documentation and communication in the patient's native language may have prevented the subsequent severe hypersensitivity reaction.

  17. Experimental study on central nervous toxicity of 'misonidazole' a hypoxic cell radiosensitizer

    International Nuclear Information System (INIS)

    Takahashi, Iku

    1981-01-01

    'Misonidazole', a radiosensitizer for hypoxic cells is expected to be applied to the treatment of malignant tumors, but its side effect becomes a subject of study, because its effective dose is close to its lethal dose. The auther performed experiments with mice on the central nervous toxicity, which is the most lethal of the side effects of Misonidazole, with the following results; 1. The abrupt death seen after the administration of a large dose of Misonidazole was attributable to the central nervous toxicity. LD 50 for d.d. strain mouse was 1.55 mg per body weight g. 2. The used mice always developed convulsion before death. But the administration of anticonvulsant failed to free them from death. 3. Autopsy findings were such abnormal ones as the degeneration and exfoliation of nerve cells and diapedetic focus. After sacrifice, however, no findings indicative of disturbance of central nerve could be detected. 4. Misonidazole, even in a small divided dose, left intracerebral retention, though slightly, indicating that its accumulation in the brain would be increased with increase in the dose. 5. The disturbance of central nerve was not exacerbated by the whole brain irradiation with Misonidazole. (author)

  18. Influence of catalase on the radiation sensitizing effect of misonidazole

    International Nuclear Information System (INIS)

    Gazso, G.L.; Dam, A.

    1985-01-01

    The radiation modifying action of misonidazole and catalase was investigated in Bacillus megaterium spores at various oxygen concentrations. Catalase (120 μg/ml) decreased the radiation sensitizing action of misonidazole. Misonidazole as an electron affinic radiation sensitizer enhanced the build up of H 2 O 2 , thus promoting the reaction with catalase. Protection by catalase was not enough to eliminate the total radiation sensitizing effect of misonidazole. (orig.)

  19. Radiation-enhanced cytotoxicity of misonidazole

    International Nuclear Information System (INIS)

    Korbelik, M.; Palcic, B.; Skarsgard, L.D.

    1981-01-01

    The effect of ionizing radiation on the toxicity of misonidazole to hypoxic mammalian cells was examined. Cell toxicity response (log surviving fraction vs time of exposure to misonidazole in hypoxia) can be approximated by a biphasic curve: an initial period of approximately zero-slope shoulder, followed by exponential decrease in survival. Radiation reduced the zero-slope shoulder of toxicity response in a dose-dependent manner and at a given dose, the shoulder totally disappeared. The slope of the exponential region of the toxic response was unaffected. The same final survival level was achieved regardless of the sequence in which radiation and mixonidazole exposure were applied to cells; in fact, there was no detectable repair of that radiation-induced damage which interacts with misonidazole toxicity (up to 24 hr). A mechanism for this interaction is proposed. Clinical implications are considered assuming that similar interaction between the two modalities takes place in vivo. Since the shoulder of toxic responses is eliminated at high radiation doses, repeated administration of radiation and misonidazole could lead to additional kill of chronically and acutely hypoxic cells, if indeed both types are present in human tumors

  20. Radiosensitization of tumors and normal tissues by combined treatment with misonidazole and heat

    International Nuclear Information System (INIS)

    Hofer, K.G.; MacKinnon, A.R.; Schubert, A.L.; Lehr, J.E.; Grimmett, E.V.

    1981-01-01

    Combination treatment of mice with misonidazole (0.5 mg/g body wt.) and hyperthermia (41.5/sup o/C for 45 mins.) produced dramatic radiosensitization in hypoxic BP-8 murine sarcoma cells. The dose modifying factor (DMF: 4.3) was such that hypoxic BP-8 cells subjected to combination therapy became more radiosensitive than untreated, fully oxygenated cell populations. In contrast, radiosensitization by combination treatment was comparatively minor or completely absent in normal body tissues such as skin (DMF: 1.57), intestine (DMF: 1.0), and bone marrow (DMF: 1.0). These results suggest that simultaneous administration of misonidazole and hyperthermia may prove an effective adjuvant to conventional clinical radiation therapy

  1. Clinical experience with the radiosensitizer misonidazole

    International Nuclear Information System (INIS)

    Kogelnik, D.; Szepesi, T.; Kaercher, K.H.; Seitz, W.

    1979-01-01

    From April 1976 to June 1978, 74 cancer patients were treated with multiple doses of misonidazole at the University Clinic for Radiotherapy and Radiobiology of Vienna. Thirtyone patients had inoperable brain tumors or high-grade astrocytomas, the remaining patients suffered from late stages of various extracerebral malignancies. All patients were hospitalized and thoroughly examined for possible side-effects of this currently most promising hypoxic cell radiosensitizer. Neurotoxicity, principally the development of peripheral neuropathies, is the most important limiting factor in the clinical application of misonidazole. With total doses of 12 g/m 2 of surface area a low and acceptable incidence of neuropathies is seen. By extension of the over-all treatment time to 6-8 weeks the total dose may be increased to 15 g/m 2 . (orig.) 891 MG/orig. 892 RDG [de

  2. Misonidazole radiosensitization in vivo: A therapeutic gain by penicillin pretreatment

    International Nuclear Information System (INIS)

    Sheldon, P.W.; Clarke, C.; Dawson, K.B.; Simpson, W.; Simmons, D.J.C.; Adams, G.E.

    1984-01-01

    Because intestinal microflora have the potential to metabolize nitroimidazole compounds (possibly to toxic species), the authors investigated their influence on the pharmacological, neurotoxic and radiosensitizing properties of misonidazole (MIS) in mice. This was done by comparing the responses obtained in 'normal' mice to those obtained in mice whose microflora had been depleted by pretreatment for 7-14 days with penicillin (PEN) at the rate of 0.5g/1 of drinking water. Bacteriological studies showed this treatment to C57B1 mice eliminated more than 99% of the flora from the caeca and, furthermore, this efficacy of penicillin was not interfered with by MIS administered IP at 0.3mg/g between days 7-14. This pretreatment resulted not only in the elimination of the caecal flora, but also in an increase in the pharmacokinetic exposure to MIS, an increase in Lewis lung tumour radiosensitization by MIS and a decrease in MIS-induced neurotoxicity. The authors conclude pretreatment with PEN can give a therapeutic gain with MIS radiosensitization. Further, assuming no direct interaction between the PEN and MIS, these findings indicate that the intestinal flora may produce neurotoxic species by their metabolism of MIS

  3. Somatosensory deficits in monkeys treated with misonidazole

    International Nuclear Information System (INIS)

    Maurissen, J.P.J.; Conroy, P.J.; Passalacqua, W.; Von Burg, R.; Weiss, B.; Sutherland, R.M.

    1981-01-01

    Misonidazole, a hypoxic cell radiosensitizer, can produce peripheral sensory disorders in humans. It has been studied in monkeys with a computer-controlled system for evaluating vibration sensitivity. Monkeys were trained to report when vibration was stimulating the finger tip. Sinusoidal vibrations of several frequencies were presented. Two monkeys were dosed with misonidazole and their vibration sensitivity tested. They received a dose of 3 g/m 2 (about 180 mg/kg) twice weekly over a period of 6 to 10 weeks. An amplitude-frequency detection function was determined for each monkey before and after drug treatment. An analysis of covariance comparing polynomial regressions was performed. A significant difference (p < 0.001) was found between control and experimental curves in both monkeys. Pharmacokinetic data indicated a half-life of the drug in blood of about 4 to 5 hr. The overall half-life for elimination did not increase throughout prolonged treatment with msonidazole. Neither motor nor sensory nerve conduction velocity was reduced after treatment

  4. Effect of misonidazole (Ro-07-0582) on the incidence of micronuclei in irradiated Ehrlich tumour ascites cells

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    Olinici, C D; Mustea, I [Institute of Oncology, Cluj (Romania)

    1978-12-01

    Misonidazole (1-(2-nitro-1-imidazole)-3-methoxy-2-propanol) was injected intraperitoneally into mice on the fifth day of development of Ehrlich ascites tumours. The animals were then /sup 60/Co ..gamma..-irradiated (100 to 400 R) and killed at 24 to 72 hours post-irradiation. Ascites tumour cells from the mice were stained by the Feulgen reaction and the incidence of micronuclei determined. Pretreatment with misonidazole induced an increase in the incidence of micronuclei in the irradiated tumour cells. This increase was most conspicuous at higher radiation doses and at 48 hours post-irradiation. The results suggest the possibility of using the micronucleus assay for the screening of substances with radio-sensitizing potential. The method would be especially suitable for the study of tumours irradiated in vivo with high doses of radiation, since cytogenetic methods present difficulties under these conditions.

  5. Kinetic aspects of misonidazole and its major metabolite in radiotherapy

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    Meering, P.G.; Maes, R.A.A. (Rijksuniversiteit Utrecht (Netherlands). Centre for Human Toxicology); Gonzalez, D.G. (Amsterdam Univ. (Netherlands). Dept. of Radiotherapy); Peperzeel, H.A. van (Rijksuniversiteit Utrecht (Netherlands). Academisch Ziekenhuis)

    1985-01-01

    Oral doses of misonidazole between 0.75 and 1.3 g/m/sup 2/ were administered during 3-5 days per week to 21 patients with various malignancies. Mean plasma levels of misonidazole and desmethylmisonidazole at the times of radiotherapy were in the range 20-50 and 2-12 mg/1 respectively. Slight accumulation of misonidazole and desmethylmisonidazole in plasma was observed with a dosage interval of 24 h. In patients with anticonvulsant comedication plasma elimination half-lives of misonidazole of 4.1-8.9 h were found. Observed side-effects were nausea and vomiting (9%), exanthema or rashes (14%) and mild peripheral neuropathy (9%).

  6. Detection of a reactive metabolite of misonidazole in human urine

    International Nuclear Information System (INIS)

    Varghese, A.J.; Whitmore, G.F.

    1984-01-01

    Chemical studies have indicated that, following reduction of misonidazole to the hydroxylamine derivative, reaction with guanosine leads to the formation of a 2-carbon addition product of guanosine. In this study, the formation of the guanosine product is used to detect the presence of a reactive metabolite of misonidazole in the urine of patients treated with misonidazole. Urine samples were incubated with [ 14 C]guanosine and the guanosine product was separated by HPLC analysis. The quantities of product vary as much as 10-fold from patient to patient and it is suggested that the assay be useful as a predictor of patients susceptible to the development of peripheral neuropathy or other effects of misonidazole

  7. Metronidazole in Scabies

    Directory of Open Access Journals (Sweden)

    V M Mathew

    1978-01-01

    Full Text Available Twenty-five patients with scabies were studied for the evaluation of metronidazole as an oral therapeutic agent. These patients were given 400 mg of metronidazole three times daily for 8 days. Good to excellent results were observed in 6 (27.27% patients, 8 (36.36% patients showed a fair response and no response was observed in 8 patients (36.36%. The significance of these results are discussed.

  8. Clinical evaluation of hypoxic cell sensitizer (Misonidazole)

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    Asakawa, Hiroshi (Miyagi Prefectural Adult Disease Center, Natori (Japan)); Watarai, Jiro; Hoshino, Toshiaki

    1984-06-01

    Clinical effectiveness and toxicity of Misonidazole were analyzed and discussed in 22 cases of carcinoma of uterine cervix, 17 cases of esophageal cancer and 11 with other malignancies treated by radiation. By clinical and histologic examination in the controlled trial, it was shown that radiation response of tumor was slightly sensitized in the treated group with this drug, compared with that in the control group. It was confirmed that there was no significant difference between radiation response of tumor in both groups. Peripheral neuropathy was a complication in 10% and toxicodermatitis in 12% even if the total dose administered was below 10 g/m/sup 2/. From these results, it was strongly suggested that this drug is not suitable in combination with simple fractionated irradiation as a hypoxic cell sensitizer.

  9. Metronidazole-induced pancreatitis.

    LENUS (Irish Health Repository)

    O'Halloran, E

    2010-01-01

    A 25-year-old caucasian lady presented to the Accident & Emergency department complaining of acute onset severe epigastric pain radiating through to the back with associated nausea and vomiting. A diagnosis of acute pancreatitis was made. Symptoms commenced after the third dose of Metronidazole therapy prescribed for a recurrent periodontal abscess. The patient described a similar episode 10 months previously. On neither occasion were any other medications being taken, there was no history of alcohol abuse and no other gastro-intestinal aetiology could be identified on imaging. Symptoms resolved quickly upon discontinuation of the antibiotic agent. We conclude therefore that Metronidazole can reasonably be identified as the only potential causative agent.

  10. Metronidazole-Induced Pancreatitis

    Directory of Open Access Journals (Sweden)

    E. O'Halloran

    2010-01-01

    Conclusion. This case provides the eighth report of Metronidazole induced pancreatitis. All of the cases were reported in females and ran a benign course.Early diagnosis, discontinuation of the drug and supportive care will lead to a successful recovery in the majority of cases.

  11. Investigation of the modifying effects of vitamin A and hypoxic cell sensitizers in radiation carcinogenesis in mice

    International Nuclear Information System (INIS)

    Mian, T.A.

    1982-01-01

    The effect of vitamin A (retinyl acetate) and three hypoxic cell sensitizers (metronidazole, misonidazole and desmethylmisonidazole) on lung tumor development in strain A mice exposed to radiation was assessed. In experiments involving vitamin A, two groups of mice were fed a low vitamin A diet (< 100 IU/100g diet) while the two other groups were fed a high vitamin A diet (800 IU/100 g diet). After two weeks one group maintained on the high vitamin A diet and one group maintained on the low vitamin A diet were given an acute dose of 500 rad of gamma radiation to the thoracic region. Mice were killed, their lungs were removed and the number of surface adenomas were counted. There was a significant increase in the number of mice bearing lung tumors and the mean number of lung tumors per mouse in the irradiated group maintained on the high vitamin A diet at 40 weeks post irradiation as compared to the irradiated group maintained on a low vitamin A diet. In the other experiment two dose levels of the hypoxic cell sensitizers, 0.2 mg/g and 0.6 mg/g, were used either alone or in combination with 900 rad of gamma radiation in a fractionated dose schedule of twice a week for three weeks. In the groups of mice which received hypoxic cell sensitizers only, the prevalence and the mean number of lung tumors per mouse were somewhat increased in the higher dose group (0.6 mg/g) of misonidazole but was not significantly different from the control animals in the other two sensitizer groups. The combination of hypoxic cell sensitizer and radiation did not show any significant enhancement of lung tumor response when compared with the group which received radiation only. The dose of radiation used in this study significantly enhanced lung tumor formation in mice when compared with the control group

  12. Clinical experiences with the radiosensitizer Misonidazol

    International Nuclear Information System (INIS)

    Bamberg, M.; Scherer, C.; Tamulevicius, P.; Streffer, C.

    1981-01-01

    The principle of action of sensitizers with electron affinity is explained and the development of these radiosensitizing substances up to the clinical of Misonidazol (MIS; Ro-07-0582) is shown. With special regard to the pharmacokinetic action of this substance, the therapeutic effects of MIS were examined in ten patients with brain tumors of high malignancy (400 mg/m 2 ) and four patients with oesophageal carcinomas (1 g/m 2 ), all these patients having reached the clinical phase III. Four other patients with recurrent brain tumors received a dose of 1 g/m 2 of MIS before each irradiation. Apart from slight neurotoxic and gastrointestinal side effects, the applicated doses of MIS were generally well tolerated. Only in one case a generalized maculopapular exanthema developed which regressed completely within few days. No correlation could be found between the subjective side effects and the plasma values determined by means of high pressure liquid chromatography (HPLC). After one to four hours following oral application, the maximum plasma concentrations were measured, the half-life (T 1/2) varying in all patients between five and ten hours. It was not possible to demonstrate an influence of dexamethasone on the plasma concentration of half-life of MIS in the brain tumor patients. The cerebrospinal fluid concentrations of MIS which may be used as an index for the concentrations in brain tumors, are closely correlated with the corresponding plasma values. There was no correlation between MIS concentrations in plasma and saliva, so that the determination of MIS in the saliva cannot be recommended as a routine method for control examinations. (orig.) [de

  13. INFLUENCE OF METRONIDAZOLE ON BIOLOGICAL ACTION OF DOXORUBICIN

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    S. A. Yagubov

    2017-01-01

    Full Text Available Purpose. Investigation of the effect of the Metronizatol on the biological effect of Doxirubicin.Materials and methods. The studies were performed in the CBA/Lac males and C57Bl/6 females mice grafted with melanoma B16 and mucinous ovarian cancer CaO‑1. Metronidazole and Doxorubicin were used in the work. The antitumor effect was assessed by tumor volume and inhibition of tumor growth.Results. The data obtained indicate that Metronidazole used in oncologic practice for the treatment and prevention of infectious complications, and as a radiosensitizer, can enhance the antitumor effect of Doxorubicin, but this effect is accompanied by a significant increase of the cytostatic toxicity. These effects are leveled by increasing the interval between injections of Metronidazole and Doxorubicin up to 4 hours.Conclusion. The enhancement of the antitumor activity of Doxorubicin under the influence of Metronidazole depends on the interval between the administration of these drugs. When Metronidazole is used in cancer patients, the possibility of enhancing the toxic effect of cytostatics should be considered when they are simultaneously exposed. Patients receiving chemotherapy should be administered antitumor drugs no earlier than 4 hours after exposure to Metronidazole

  14. Misonidazole neurotoxicity in the mouse: evaluation of functional, pharmacokinetic, electrophysiologic and morphologic parameters

    International Nuclear Information System (INIS)

    Conroy, P.J.; Von Burg, R.; Passalacqua, W.; Penney, D.P.; Sutherland, R.M.

    1979-01-01

    The neurotoxic effects of chronic administration of misonidazole (0.3 mg/g/day, 5 times weekly) were investigated in Balb/cKa mice over 12 weeks; a variety of measurements were used, including functional and clinical performance, morphologic, electrophysiologic and pharmacokinetic parameters. The half life of drug for a single dose was greater in brain (3 hrs) compared to serum (1.2 hrs); these values decreased to 1.9 hrs and 1.0 hrs respectively after 3 weeks. Misonidazole induced a peripheral lesion after three weeks with a total administered dose of 13.5 g/m 2 or exposure dose of 57 to 75 mM X hrs, which is similar to the doses that cause neuropathy in humans. There was some suggestion of a central neurological deficit related to locomotor control and balance; however, no gross morphological damage was found in the brain. The sequence of effects demonstrated began at 3 to 4 weeks and included: 1) morphologic damage to peripheral nerves; 2) hyperactivity and listlessness; 3) a decrease in rotarod retention time which reached a value 50% of that of saline injected control mice at 8 to 10 weeks; 4) walking on tip-toes with a slightly hunched back (4 to 6 weeks); and 5) an increase in hind foot splay (6 to 7 weeks). The morphologic damage primarily involved the more distal portions of the nerves supplying the interosseous muscles and footpads of the hind limbs. The damage was more severe and progressed more rapidly with time in these distal areas compared to the more proximal regions of the nerves. No marked changes were found in nerve conduction velocity although neuropathy produced by acrylamide produced significant decreases. The changes in neurological parameters reported here may be useful in the further evaluation of hypoxic cell radiosensitizers

  15. UV spectrophotometry of the Metronidazole

    Directory of Open Access Journals (Sweden)

    O. I. Panasenko

    2013-10-01

    Full Text Available Objective. The purpose of this research was to study the UV spectrum of Metronidazole in different polarity solvents (water, 95 % ethanol, 0,1 M sodium hydroxide, 0,1 M hydrochloric acid and 5 M sulfuric acid solution, to establish the relationship between chemical structure of the analyzed compounds and the nature of their electronic spectrum. In addition, a detailed study of the ultraviolet spectra of Metronidazole in different solutions enables to select the optimal wavelength and a thinner design for Metronidazole in substance and dosage forms. Materials and methods. Spectrophotometer SPECORD 200-222U214 has been used for study of the UV spectra of Metronidazole, the quantitative methods were used. Measuring of the absorption of Metronidazole solutions has been carried out in quartz cuvettes with a layer thickness of 10 mm. Due to the fact that the test material shows selective absorption in the ultraviolet spectra, model compounds were studied at a concentration of 1 mg%. Study of electronic spectra was performed in the range of 200 to 400 nm, and the curve has been constructed in coordinates A = f (λ. It has been used water, 95% ethanol, 0,1 M NaOH, 0,1 M HCl and 5 M H2SO4 as solvents. The content of Metronidazole in substance and dosage forms calculated with the equations according to SPU. The results. Study of the UV spectra of Metronidazole and its model compounds showed that in short-wave part of spectrum due to absorption and excitation electrons of imidazole ring were transferred, and in long-wave – conjugation chromophore imidazole cycle and nitro group as electron acceptor occurred. Analysis of the UV spectra of Metronidazole enables to determine a maximum of the analytical quantification of the medicine. Conclusions. Metronidazole UV spectra in water, 95% ethanol, 0,1 M solution of NaOH, 0,1 M solution of HCl and 5 M solution of H2SO4 have been studied. Metronidazole UV spectra are characterized by two absorption bands in the

  16. [Tetracyclines, sulfonamides and metronidazole].

    Science.gov (United States)

    Pérez-Trallero, Emilio; Iglesias, Luis

    2003-11-01

    Tetracyclines form a group of natural and semisynthetic products that acts inhibiting the bacterial protein synthesis. They are bacteriostatic agents, exhibiting activity against a wide range of organisms, but they are at the present of limited use because of their acquired resistance. Doxycycline is currently the most frequently used tetracycline in human medicine and it is included in the List of Essential Medicines of the World Health Organization. Sulfonamides are synthetic, broad-spectrum bacteriostatic antibiotics. They were the first effective systemic antimicrobial agents. Their mode of action is based on the inhibition of DNA synthesis. Due to their toxicity and high adquired resistance their use is currently very low. Metronidazole is the main compound of 5-nitroimidazole family. It is a very active bactericidal antibiotic against anaerobic and some microaerophilic bacteria and it is still very useful in the treatment of bacterian and parasitic infections.

  17. Optimization of Metronidazole Emulgel

    Directory of Open Access Journals (Sweden)

    Monica Rao

    2013-01-01

    Full Text Available 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 ( and spreadability (. Mathematical equations and response surface plots were used to relate the dependent and independent variables. The regression equations were generated for responses and . 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.

  18. Phenytoin shortens the half-life of the hypoxic cell radiosensitizer misonidazole in man: implications for possible reduced toxicity

    International Nuclear Information System (INIS)

    Workman, P.; Bleehen, N.M.; Wiltshire, C.R.; Cambridge Univ.

    1980-01-01

    Results are described of a preliminary study of the effects of phenytoin, (commonly used as an anticonvulsant in the treatment of patients with brain tumours), on the plasma pharmacokinetics of misonidazole (MISO) in man. Previous studies have shown that pretreatment with phenytoin shortens the half-life of MISO in dogs and mice by induction of drug metabolizing enzymes, and also reduces the acute lethal effects of MISO in mice. In this study patients with various types of malignancy and with cerebral metastases were given MISO before and after a course of phenytoin. Others were assessed as controls without phenytoin administration. Plasma concentrations of MISO were determined in blood samples taken before and at various times after administration. A summary of the pharmacokinetic data obtained is given. (author)

  19. Radiosensitization of mammalian cells by misonidazole and oxygen: DNA damage exposed by Micrococcus luteus enzymes

    International Nuclear Information System (INIS)

    Skov, K.A.; Palcic, B.; Skarsgard, L.D.

    1979-01-01

    When misonidazole is present during irradiation of hypoxic mammalian cells, an enhancement of single-strand breaks (SSB) in DNA is observed. Oxygen also enhances SSB, presumably in a manner similar to that of misonidazole. The dose-modifying factor (DMF) for 15 mM misonidazole was found to be 3.4, compared to an oxygen enhancement ratio (OER) of 3.5. Another class of DNA damage, namely, sites exposed by an extract of Micrococcus luteus, was examined. Radiation-induced M. luteus extract-sensitive sites (MLS) were also found to be enhanced by the presence of misonidazole or molecular oxygen. The DMF for this damage by 15 mM misonidazole was 1.6 while the OER was 2.5. The ratio of MLS to SSB is approximately 1.25 under hypoxia, 0.9 in the presence of oxygen, and 0.6 in the presence of 15 mM misonidazole under hypoxic conditions. Incubation with misonidazole under conditions which are toxic to mammalian cells (37 0 C, hypoxia), and which result in many SSB, produces no detectable lesions sensitive to the M. luteus extract

  20. Reaction of misonidazole with DNA radicals and its effect on the template activity of DNA

    International Nuclear Information System (INIS)

    Endoh, Daiji; Kuwabara, Mikinori; Sato, Fumiaki; Yoshii, Giichi.

    1985-01-01

    After calf thymus DNA was gamma-irradiated in the solid state in vacuo and subsequently dissolved in aqueous solution containing misonidazole (3 mM) under hypoxic condition, the frequency of single-strand breaks and alkali-labile sites in DNA and the amount of misonidazole bound to DNA were measured. The presence of misonidazole converted the precursor radicals, which otherwise results in single-strand breaks, to alkali-labile sites, and the amount of alkali-labile sites increased linearly with increasing radiation dose. The amount of misonidazole bound to DNA also increased linearly with increasing radiation dose. The biological meaning of the changes in the frequency of single-strand breaks and alkali-labile sites by the reaction of misonidazole with DNA radicals and of binding misonidazole with DNA was examined using a model system to measure the template activity of DNA for RNA synthesis in vitro. The conversion of DNA radicals to alkali-labile sites protected the radiation-induced decrease in the template activity of DNA, while the adduct formation of misonidazole had no effect on it. (author)

  1. Serial study of the concentration of misonidazole in human tumors correlated with histologic structure

    International Nuclear Information System (INIS)

    Rich, T.A.; Dische, S.; Saunders, M.I.; Stratford, M.R.L.; Minchinton, A.

    1981-01-01

    Multiple biopsies were obtained from eight patients with malignant tumors during a course of fractionated radiotherapy. An analysis of the total 2-nitroimidazole concentration and a histological examination of the biopsy sample was done on material which appeared macroscopically similar. The parts of the tumor biopsies showing necrosis were found to contain much lower concentrations of nitroimidazole when compared with those found in the samples with well-vascularized and apparently viable tumor. During the course of irradiation changes in misonidazole concentrations were not found when similar histological material was examined. The low values of misonidazole in necrotic regions in human tumors may partly account for the wide variation of misonidazole concentrations reported in the literature (percent tumor/plasma, mean 62.9 +- 34.4 STD). The clinical significance of the microscopic distribution of misonidazole in tumors in unknown but further work in this area may aid in predicting the usefulness of future radiosensitizers

  2. Misonidazole in patients receiving radical radiotherapy: pharmacokinetic effects of phenytoin tumor response and neurotoxicity

    International Nuclear Information System (INIS)

    Moore, J.L.; Biol, F.I.; Patterson, I.C.M.; Dawes, P.J.D.K.; Henk, J.M.

    1982-01-01

    In 1978, a pilot study began of 29 patients with advanced tumors of the head and neck. The study showed an initial peripheral neuropathy rate of 55%, despite a dose limitation of 12 g/m 2 of misonidazole. Tumor response at 9 months was most encouraging. We are now able to examine tumor response and persistence of neuropathy in these patients 2 1/2 years after radical radiotherapy. The results are comparable with those obtained with hyperbaric oxygen in a clinical trial at this center during the 1970's. Neuropathy was a serious side effect but the drug phenytoin has been shown to shorten the half-life of misonidazole. We have examined the effect of phenytoin on the pharmacokinetics of misonidazole in 13 patients who received radical radiotherapy for advanced head and neck tumors or oesophageal tumors. Misonidazole was given in multiple doses, i.e. daily or weekly as it would be used in conventional therapy. Phenytoin was given either daily throughout treatment, or it was withdrawn during treatment. There were dramatic changes in the half-life of misonidazole, but the concentration at the time of irradiation was little affected. The significant changes in the half-life of misonidazole and the increased concentration of the metabolite desmethylmisonidazole are discussed

  3. Effect of size of lymph node metastases on the radiation response: influence of misonidazole

    International Nuclear Information System (INIS)

    Courdi, A.; Malaise, E.P.

    1980-01-01

    Metastatic lymph nodes of EMT6 tumors growing in athymic nude mice were used at different sizes and their radiosensitivity was tested with the in vitro colony method. Following the administration of 1250 rad, the surviving fraction in air-breathing animals was found to be dependent on the size of these metastases, expressed either in weight or in cell yield per lymph node. The increasing radioresistance with increase in size was probably due to the presence of higher hypoxic fraction in big nodes (0.43 in nodes weighing more than 320 mg vs 0.10 in nodes less than 80 mg). The surviving fraction after irradiation in acutely hypoxic conditions (asphyxiated animals) or in fully oxygenated ones (in vitro) was not size dependent. Great variations were observed in the radiosensitivity of small metastatic nodes, whereas bigger metastases had a more homogeneous response. The effect of the radiosensitizer misonidazole at a dose of 0.3 mg/g was assessed on lymph node metastases of different sizes. In the presence of the drug, the survival level of big and small metastases differed by a factor of 2.2, as opposed to 4.3 in untreated metastases. This suggests that the radiosensitization is less pronounced in metastases containing a smaller hypoxic fraction

  4. Misonidazole in fractionated radiotherapy: are many small fractions best

    International Nuclear Information System (INIS)

    Denekamp, J.; McNally, N.J.; Fowler, J.F.; Joiner, M.C.

    1980-01-01

    The largest sensitizing effect is always demonstrated with six fractions, each given with 2 g/m 2 of misonidazole. In the absence of reoxygenation a sensitizer enhancement ratio of 1.7 is predicted, but this falls to 1.1-1.2 if extensive reoxygenation occurs. Less sensitization is observed with 30 fractions, each with 0.4 g/m 2 of drug. However, for clinical use, the important question is which treatment kills the maximum number of tumour cells. Many of the simulations predict a marked disadvantage of reducing the fraction number for X rays alone. The circumstances in which this disadvantage is offset by the large Sensitizer enhancement ratio values with a six-fraction schedule are few. The model calculations suggest that many small fractions, each with a low drug dose, are safest unless the clinician has some prior knowledge that a change in fraction number is not disadvantageous. (author)

  5. Radiation Therapy Oncology Group clinical trials with misonidazole

    International Nuclear Information System (INIS)

    Wasserman, T.H.; Stetz, J.; Phillips, T.L.

    1981-01-01

    This paper presents a review of the progressive clinical trials of the hypoxic cell radiosensitizer, misonidazole, in the Radiation Therapy Oncology Group (RTOG). Presentation is made of all the schemas of the recently completed and currently active RTOG Phase II and Phase III studies. Detailed information is provided on the clinical toxicity of the Phase II trials, specifically regarding neurotoxicity. With limitations in drug total dose, a variety of dose schedules have proven to be tolerable, with a moderate incidence of nausea and vomiting and mild peripheral neuropathy or central neuropathy. No other organ toxicity has been seen, specifically no liver, renal or bone marrow toxicities. An additional Phase III malignant glioma trial in the Brain Tumor Study Group is described

  6. Metronidazole distribution following intraarterial administration

    International Nuclear Information System (INIS)

    Konoplyannikov, A.G.; Grigor'ev, A.N.; Zubov, O.G.

    1984-01-01

    An attempt to achieve a high local concentration of metronidazole in tissues at intraarterial administration in experiments with dogs is made. Intraarterial administration makes it possible to ''saturate'' with a radiosensitizer first of all tissues fed by an artery in question. Administration of the drug to a vessel feeding the tumor would, probably, result in a sharp increase in its concentration in the malignant neoplasm as compared with the rest organs and tissues, which should amplify the radiosensitizing effect

  7. Hypoxic fraction and binding of misonidazole in EMT6/Ed multicellular tumor spheroids

    International Nuclear Information System (INIS)

    Franko, A.J.

    1985-01-01

    Misonidazole has been shown to bind selectively to hypoxic cells in tissue culture and to cells which are presumed to be chronically hypoxic in EMT6 spheroids and tumors. Thus it has considerable potential as a marker of hypoxic cells in vivo. To further evaluate this potential EMT6/Ed spheroids were used to quantitate misonidazole binding under conditions which resulted in hypoxic fractions between 0 and 1. The patterns of binding of 14 C-labeled misonidazole determined by autoradiography were consistent with the regions of radiobiological hypoxia as predicted by oxygen diffusion theory. The overall uptake of 3 H-labeled misonidazole by spheroids correlated well with the hypoxic fraction, although binding to aerobic cells and necrotic tissue contributed appreciably to the total label in the spheroids. It is concluded that misonidazole is an excellent marker of hypoxia in EMT6/Ed spheroids at the microscopic level, and the total amount bound per spheroid provides a potentially useful measure of the hypoxic fraction

  8. The role of microsomal enzyme inducers in the reduction of misonidazole neurotoxicity

    International Nuclear Information System (INIS)

    Jones, D.H.; Bleehen, N.M.; Workman, P.; Smith, N.C.

    1983-01-01

    It has been shown that phenytoin, 300 mg daily for one week, produces consistent hepatic microsomal enzyme induction, resulting in a decrease of 25% in misonidazole half-life, without causing any toxicity per se. A longer period of administration gives only a slightly greater induction. Phenobarbitone in a daily dose of 90 mg causes a reduction of 18% and 23% in misonidazole half-life after 1 and 2 weeks' pre-treatment respectively, but is less suitable clinically because of its sedative effect. A further series of studies using phenytoin as the inducing agent has shown that, despite adequate enzyme induction and increased misonidazole metabolism, it is impossible to increase the total dose of misonidazole beyond the usually accepted value of 12 g/m 2 because of unacceptable neuropathy (a rate of 50% at a dose of 14 g/m 2 over three weeks). In single doses of above 3.0-4.0 g of misonidazole, severe nausea and vomiting are prominent, so that this side effect is a determining factor in the treatment fractionation. Audiometric studies show no correlation between the incidence of peripheral neuropathy and abnormal audiograms, and have no value in the early prediction of neurotoxicity. (author)

  9. Role of microsomal enzyme inducers in the reduction of misonidazole neurotoxicity

    Energy Technology Data Exchange (ETDEWEB)

    Jones, D.H.; Bleehen, N.M.; Workman, P.; Smith, N.C. (Cambridge Univ. (UK). Dept. of Clinical Oncology and Radiotherapeutics; Addenbrooke' s Hospital, Cambridge (UK))

    1983-11-01

    It has been shown that phenytoin, 300 mg daily for one week, produces consistent hepatic microsomal enzyme induction, resulting in a decrease of 25% in misonidazole half-life, without causing any toxicity per se. A longer period of administration gives only a slightly greater induction. Phenobarbitone in a daily dose of 90 mg causes a reduction of 18% and 23% in misonidazole half-life after 1 and 2 weeks' pre-treatment respectively, but is less suitable clinically because of its sedative effect. A further series of studies using phenytoin as the inducing agent has shown that, despite adequate enzyme induction and increased misonidazole metabolism, it is impossible to increase the total dose of misonidazole beyond the usually accepted value of 12 g/m/sup 2/ because of unacceptable neuropathy (a rate of 50% at a dose of 14 g/m/sup 2/ over three weeks). In single doses of above 3.0-4.0 g of misonidazole, severe nausea and vomiting are prominent, so that this side effect is a determining factor in the treatment fractionation. Audiometric studies show no correlation between the incidence of peripheral neuropathy and abnormal audiograms, and have no value in the early prediction of neurotoxicity.

  10. Treatment of trichomoniasis with metronidazole rectal suppositories

    Science.gov (United States)

    Panja, S K

    1982-01-01

    Since a single dose of metronidazole in suppository form is very effective in the prevention of postoperative Gram-negative anaerobic infections, 84 patients with vaginal trichomoniasis were treated with metronidazole suppositories (two 1-g suppositories in a single dose). The cure rate in this series was 94%. PMID:7104657

  11. Treatment of trichomoniasis with metronidazole rectal suppositories

    OpenAIRE

    Panja, S K

    1982-01-01

    Since a single dose of metronidazole in suppository form is very effective in the prevention of postoperative Gram-negative anaerobic infections, 84 patients with vaginal trichomoniasis were treated with metronidazole suppositories (two 1-g suppositories in a single dose). The cure rate in this series was 94%.

  12. Radioprotective effect of misonidazole (Ro-07-0582) on normal canine rectum

    Energy Technology Data Exchange (ETDEWEB)

    Stryker, J.A.; Albert, A.; Abt, A.B.

    1980-10-01

    A single 1500 rad (=15 Gy) dose of 10-MeV X-rays was administered to the pelvis of 20 mongrel dogs. Ten received misonidazole (Ro-07-0582), 100 mg/kg p.o., 4 hours pre-irradiation. Serum misonidazole levels immediately pre-irradiation were 43 +- 10 ..mu..g/ml (mean +- SD). The dogs were euthanized within 3 months post-irradiation. Each rectal specimen was studied for anatomic and histologic pathology and was assigned a Pathologic Alteration Score (PAS) of 1, 2, or 3 in order of increasing severity. The PAS of the rectal specimens from the drug group was 1.6 +- 0.7, and that of the controls 2.3 +- 0.8. The PAS of the drug group was significantly lower than the control group (P = 0.008). The data suggest that misonidazole is a radioprotector for normal tissue.

  13. The enhanced cytotoxicity of misonidazole in the thiol depleted state - An oxygen dependent mechanism

    International Nuclear Information System (INIS)

    Tuttle, S.W.; Varnes, M.E.; Donahue, L.; Biaglow, J.E.

    1985-01-01

    Incubating A549 cells in the presence of L-buthionine-S, R-sulfoximine and misonidazole under aerobic conditions results in lowered rates of cell growth and greater cytotoxicity than is seen with either drug alone. The authors previously demonstrated the accumulation of hydrogen peroxide from cells treated with misonidazole following the inhibition of GSH-peroxidase with thiol depleting agents. They hypothesize that the enhancement of misonidazole toxicity by L-BSO results from the increased exposure to hydrogen peroxide, and the possible formation of the highly reactive hydroxyl radical in the presence of trace metals via Fenton chemistry. Support for this hypothesis comes from their observations that addition of radical scavengers (such as SOD and catalase) and nutritional antioxidants (vitamin E) to the culture medium will partially inhibit the cytotoxic effects. Further work is being done to measure the products of reaction of toxic oxygen species with cellular macromolecules, i.e. lipids

  14. Voltammetric Behaviour of Metronidazole at Mercury Electrodes

    Directory of Open Access Journals (Sweden)

    La-Scalea Mauro A.

    1999-01-01

    Full Text Available Metronidazole is the most important drug of the group of 5-nitroimidazoles and possesses toxicity to anaerobic micro-organisms DNA being the main target for their biological action. The mechanism of biological action of metronidazole is dependent upon the nitro group reduction process. The reduction of metronidazole is pH dependent in acid medium and four electrons are involved in the complete reduction to the hydroxylamine derivative. In aprotic medium the reduction of the metronidazole occurs in two steps, the first involving one electron to form the nitro radical and the second step involving three more electrons until the formation of the hydroxylamine derivative. In this paper the mechanism of reduction of metronidazole was studied by using the voltammetric techniques: d.c. polarography, differential pulse polarography and cyclic voltammetry using the mercury drop as the working electrode.

  15. Misonidazole combined with hyperfractionation in the management of malignant glioma

    International Nuclear Information System (INIS)

    Fulton, D.S.; Urtasun, R.C.; Shin, K.H.

    1984-01-01

    Multiple daily fractionated radiation therapy (MDF) may be more effective than conventionally fractionated radiation therapy (CF) in the treatment of malignant glioma. The hypoxic cell sensitizer misonidazole (MISO) could be more effective when employed with small fractions of radiation every 4 hours to take advantage of the long half-life of the drug. To evaluate MDF and MDF in combination with MISO, a randomized prospective trial was initiated. Between January 1981, and December 1982, patients with histologically verified astrocytoma with anaplastic foci or glioblastoma multiforme were randomized to CF, MDF and MDF in combination with MISO. In January 1983, the CF arm was dropped and a high dose MDF arm added. CCNU chemotherapy was given at the time of tumor progression. Median survival was 29 weeks for CF, 45 weeks for MDF and 50 weeks for MDF plus MISO. Survival was significantly improved for patients treated with MDF compared to patients treated with CF. The addition of MISO to MDF did not result in further improvement in survival. Acute toxicity was acceptable

  16. Mechanism of melphalan crosslink enhancement by misonidazole pretreatment

    International Nuclear Information System (INIS)

    Taylor, Y.C.; Sawyer, J.M.; Hsu, B.; Brown, J.M.

    1984-01-01

    Sensitization of Chinese hamster ovary cells to melphalan (L-PAM) toxicity by prior treatment with misonidazole is associated with increased levels of DNA crosslinks believed to be the critical lesion for bifunctional alkylating agent toxicity. Enhanced L-PAM crosslinking of DNA could occur by a variety of mechanisms in MISO-pretreated cells including: (1) increased transport or binding of L-PAM, (2) decreased repair of L-PAM monoadducts which would allow more time for their conversion to crosslinks, (3) decreased crosslink repair (unhooking of one arm), or (4) chemical modification of the DNA structure, presumably by bound MISO derivatives, such that crosslink formation is facilitated. Previous studies have eliminated mechanisms (1) and (3). Mechanism (4) was investigated by following MISO-pretreatments of whole cells with L-PAM treatments of the isolated DNA from these cells. Treatment of bare DNA with L-PAM modeled very well the crosslinking behavior in whole cells although it was somewhat more efficient. In the presence of double stranded DNA and absence of repair systems during and after the L-PAM exposure, it was determined that MISO-pretreatments did not increase the crosslinking efficiency of L-PAM

  17. Inhibition of glycolysis by misonidazole in hypoxic cells

    International Nuclear Information System (INIS)

    Ling, L.; Sutherland, R.

    1984-01-01

    Inhibition of glycolysis has been postulated to be a mechanism of misonidazole (MISO) toxicity in hypoxic cells. To investigate the effect of MISO on glycolysis, glucose transport and its consumption and lactate formation were measured. Exponential EMT6 cells (10/sup 6/ cells/ml) were made hypoxix by continuous gassing in 3% CO/sub 2/ in N/sub 2/. They were then treated with 5mM MISO for various times, then washed and analysed for their rates of anaerobic glycolysis. Glucose and lactate content were determined enzymatically. The rates of both glucose consumption and lactate formation decreased after 30 min hypoxic incubation with MISO. After 90 min, the rates were not measurable even though the cells still excluded Trypan Blue. There was, however, a parallel decrease in plating efficiency. These data suggest that the inhibition of glycolysis is an important mechanism of hypoxic toxicity of MISO. To locate the site of inhibition, studies were initiated to look at glucose transport by following the uptake of /sup 14/-C-3-0-methyl-glucose, a nonmetabolised glucose analog. Results obtained so far indicate that up to 90 min of hypoxic incubation with MISO, there was no change in the kinetics of the uptake of his analog. Therefore, the results showed that in hypoxic cells treated with MISO, the glucose transport system was unaffected. However, there was a rapid decrease in anaerobic glycolysis

  18. Cambridge glioma trial of misonidazole and radiation therapy with associated pharmacokinetic studies

    International Nuclear Information System (INIS)

    Bleehen, N.M.

    1980-01-01

    Fifty-five patients with grade 3 and 4 supratentorial astrocytomas, were randomized into a three-limb study. At 9 months after the last treatment there were no differences in survival between the treatment groups. No cases of peripheral neuropathy were seen. Investigations into the possible cause of this are presented. It is thought that microsomal enzyme induction by the anticonvulsants phenobarbitone and phenytoin resulted in increased 0-demethylation of the misonidazole. Clinical data to confirm this view are presented. Current MRC protocols of misonidazole studies on gliomas and carcinomas of the cervix and head and neck are summarized

  19. Influence of misonidazole, anaesthesia, clamping of the leg and stress of the animal during treatment on the radiation-induced skin reaction of mouse feet

    International Nuclear Information System (INIS)

    Wondergem, J.; Haveman, J.; Schueren, E. van der

    1982-01-01

    The influence of anaesthesia and misonidazole on the 'acute' (average of the scores between day 10 and 30) and 'late' (average of the scores between day 100 and 120) skin reaction of the feet of mice was investigated under two different conditions. Firstly, the legs were kept untaped in the radiation field; secondly, the legs were fixed with surgical tape on the backscatter block. Irradiation was carried out by X-radiation at a dose of 35 Gy. Results showed that stress in unanaesthetized animals has a large influence on the radiation response of mouse skin. Adequate treatment conditions, tranquillizers or anaesthesia can compensate for this factor. Taping of the animals' legs, resulting in clamping, interferes with the assessment of these modalities. No influence of misonidazole on the skin reaction could be demonstrated in conditions where no artificial hypoxia was induced. The importance of taking experimental conditions into account is pointed out for the correct assessment of the effect of radiosensitizers and possibly other anticancer drugs. (U.K.)

  20. Clinical experience with intravenous misonidazole for carcinoma of the esophagus: results in attempting radiosensitization of each fraction of exposure

    International Nuclear Information System (INIS)

    Schwade, J.G.; Kinsella, T.J.; Kelly, B.; Rowland, J.; Johnston, M.; Glatstein, E.

    1984-01-01

    By using intravenous misonidazole, a hypoxic cell radiosensitizer, the authors attempted to test the hypothesis of hypoxia as the basis of the relatively poor results seen with radiation therapy in the treatment of carcinoma of the thoracic esophagus. As the peripheral neuropathy of misonidazole was well recognized, they felt that an adequate dose of misonidazole could be given approximately ten times before peripheral neuropathy would necessitate its discontinuation. Because of a desire to maximize any possible effects of radiosensitization, it was decided to administer misonidazole with each fraction of radiation, attempting to deliver curative radiation therapy with only ten fractions of radiation. The authors thus devised a scheme of radiation consisting of 400 rad twice a week for 5 weeks, a total of 4000 rad. Originally the attempt was made to utilize preoperative radiation therapy and assess the histologic specimens for efficacy. However, major pulmonary toxicity caused revision of that plan. Twenty six patients were treated with radiotherapy alone without surgery, 12 of the patients being randomized to receive intravenous misonidazole with 10 fractions of 400 rad each. In terms of partial response, complete response, local control, and long-term survival, there was no suggestion of any benefit of intravenous misonidazole in these patients. As a consequence, although the number of study patients was small, the investigation was discontinued. Possible explanations for the failure to demonstrate any benefit of misonidazole are discussed

  1. Metronidazole

    Directory of Open Access Journals (Sweden)

    Jean-Marc Bohbot

    2010-01-01

    , 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.

  2. Metronidazole

    Science.gov (United States)

    ... the reproductive system, gastrointestinal (GI) tract, skin, heart, bone, joint, lung, blood, nervous system, and other areas ... to your pharmacist or contact your local garbage/recycling department to learn about take-back programs in ...

  3. High-dose irradiation and misonidazole in the treatment of malignant gliomas

    International Nuclear Information System (INIS)

    Kogelnik, H.D.; Kaercher, K.H.; Szepesi, T.; Schratter-Sehn, A.V.

    1982-01-01

    Thirty-three patients with grade III and IV supratentorial astrocytomas who were entered into a radomized two-arm study to evaluate the effect of misonidazole in conjunction with postoperative irradiation are available for analysis. All patients received the same radiation dose: 6650 rads (43 MeV photons) in 31 fractions over 7 1/2 weeks. Misonidazole was given orally 4 to 5 hours before irradiation on those treatment days when fractional radiation doses of 400 rads were used. The cumulative dose of misonidazole was 27 g, corresponding to 12.6 to 16.4 g/m 2 . With a minimum follow-up time of one year, median survival for patients receiving postoperative irradiation had a median survival of 57.1 weeks. The difference in the distribution of survival times between both groups is statistically significant (p < 0.02). From an analysis of variance for age, it cannot be ruled out that the survival difference between the two groups is at least partly due to differences in ages. Side effects of misonidazole were minimal, with only 2 patients experiencing mild paresthesias and 4 noting a transient tinnitus

  4. Radiation-induced energy migration within solid DNA: The role of misonidazole as an electron trap

    International Nuclear Information System (INIS)

    Al-Kazwini, A.T.; O'Neill, P.; Adams, G.E.; Fielden, E.M.

    1990-01-01

    The in-pulse luminescence emission from solid DNA produced upon irradiation with electron pulses of energy below 260 keV has been investigated in vacuo at 293 K to gain an insight into the existence of radiation-induced charge/energy migration within DNA. The DNA samples contained misonidazole in the range 3 to 330 base pairs per misonidazole molecule. Under these conditions greater than 90% of the total energy is deposited in the DNA. The in-pulse radiation-induced luminescence spectrum of DNA was found to be critically dependent upon the misonidazole content of DNA. The luminescence intensity from the mixtures decreases with increasing content of misonidazole, and at the highest concentration, the intensity at 550 nm is reduced to 50% of that from DNA only. In the presence of 1 atm of oxygen, the observed emission intensity from DNA in the wavelength region 350-575 was reduced by 35-40% compared to that from DNA in vacuo. It is concluded that electron migration can occur in solid mixtures of DNA over a distance of up to about 100 base pairs

  5. diffusion of metronidazole released through cellulose membrane

    African Journals Online (AJOL)

    prof kokwaro

    was determined using dialyzing cellulose membrane in a dissolution tester. Glycerin, a permeation ... An attempt has been made in the present ... Materials. Metronidazole USP was donated by Cosmos. Pharmaceutical Ltd., Nairobi, Kenya.

  6. Isolate resistance of Blastocystis hominis to metronidazole.

    Science.gov (United States)

    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.

  7. In vivo studies on the experimental tumour sarcoma 180 in order to determine the therapeutic efficiency of gamma and neutron irradiation combined with hyperthermia and misonidazole

    International Nuclear Information System (INIS)

    Weber, H.J.

    1982-01-01

    The influence of hyperthermia and/or Misonidazole on the therapeutic effect of gamma and neutron irradiation was investigated for the solid experimental tumour Sarcoma 180 in NMRI mice. Apart from the common biological parameters (tumour volume, growth retardation, tumour regression), also cellular effects and cell metabolism were studied in vivo by I-UdR lavelling without disturbing the tumour/host interaction. Sequential double labelling with 125 I-UdR and 131 I-UdR before treatment and measurement of rates of activity loss afterwards yielded information on cell metabolism and therapeutic efficiency. The influence of different therapies on the proliferation activity was assessed by injection of 125 I-UdR at different times after treatment, followed by measurements of the incorporation rate. The diagnostic value of the methods of measurement and the possibility of transferring the findings of animal experiments to clinical practice were investigated. (orig./MG) [de

  8. Susceptibility of Porphyromonas gingivalis in biofilms to amoxicillin, doxycycline and metronidazole

    DEFF Research Database (Denmark)

    Larsen, T.

    2002-01-01

    Biofilm, Porphyromonas gingivalis, susceptibility testing, amoxicillin, doxycycline, metronidazole......Biofilm, Porphyromonas gingivalis, susceptibility testing, amoxicillin, doxycycline, metronidazole...

  9. Influence of misonidazole on the radiation response of murine tumors of different size: possible artifacts caused by pentobarbital sodium anesthesia

    International Nuclear Information System (INIS)

    Wondergem, J.; Haveman, J.; van der Schueren, E.; van den Hoeven, H.; Breur, K.

    1981-01-01

    The radiosensitivity of a transplantable murine adenocarcinoma decreased with increasing tumor volume. In unanesthetized mice this phenomenon (based on the effect of the hypoxic cell sensitizer misonidazole), in the range of volumes studied, can largely be explained by the appearance of hypoxic cells in the tumor during growth. The use of pentobarbital sodium during irradiation is confiremd to be a disturbing factor, as it may increase the hypoxic cell fraction in the tumors. No evidence was found for a direct radiochemical protection because of pentobarbital sodium. The radioprotective effect of the anesthetic could only be demonstrated in conditions where there is already a fraction of hypoxic cells; no influence of the anesthesia was found in small tumors in which the fraction of hypoxic cells was relatively small. This may account for the previously conflicting data on the influence of pentobarbital sodium anesthesia. The vascularization of larger tumors is apparently inferior to smaller tumors and this has important repercussions in the case of anesthesia. Changes in blood flow induced by pentobarbital sodium in larger tumors cause an insufficient oxygenation and hence acute hypoxia

  10. Degradation kinetics of metronidazole and its mutual prodrug with ...

    African Journals Online (AJOL)

    Dr Renu Chadha

    present paper utilizes this technique to monitor the hydrolytic degradation of metronidazole ... the antiprotozoal and anaerobic antibacterial effects of metronidazole with ... The catalytic rate constant for hydrogen ion (kH) and hydroxyl ion (kOH) ...

  11. Plasma hydroxy-metronidazole/ metronidazole ratio in hepatitis C virus-induced liver disease

    Directory of Open Access Journals (Sweden)

    M.A.M. Marchioretto

    2005-03-01

    Full Text Available It has been suggested that the measurement of metronidazole clearance is a sensitive method for evaluating liver function. The aim of this study was to evaluate the usefulness of plasma hydroxy-metronidazole/metronidazole ratios as indicators of dynamic liver function to detect changes resulting from the various forms of chronic hepatitis C virus (HCV infection. A total of 139 individuals were studied: 14 healthy volunteers, 22 healthy, asymptomatic, consecutive anti-HCV-positive HCV-RNA negative subjects, 81 patients with chronic hepatitis C (49 with moderate/severe chronic hepatitis and 34 with mild hepatitis, and 20 patients with cirrhosis of the liver. HCV status was determined by the polymerase chain reaction. Plasma concentrations of metronidazole and its hydroxy-metabolite were measured by reverse-phase high-performance liquid chromatography with ultraviolet detection in a blood sample collected 10 min after the end of a metronidazole infusion. Anti-HCV-positive HCV-RNA-negative individuals demonstrated a significantly reduced capacity to metabolize intravenously infused metronidazole compared to healthy individuals (0.0478 ± 0.0044 vs 0.0742 ± 0.0232. Liver cirrhosis patients also had a reduced plasma hydroxy-metronidazole/metronidazole ratio when compared to the other groups of anti-HCV-positive individuals (0.0300 ± 0.0032 vs 0.0438 ± 0.0027 (moderate/severe chronic hepatitis vs 0.0455 ± 0.0026 (mild chronic hepatitis and vs 0.0478 ± 0.0044 (anti-HCV-positive, HCV-RNA-negative individuals. These results suggest an impairment of the metronidazole metabolizing system induced by HCV infection that lasts after viral clearance. In those patients with chronic hepatitis C, this impairment is paralleled by progression of the disease to liver cirrhosis.

  12. Comparison of the incidence of oncogenic transformation produced by x-rays, misonidazole, and chemotherapy agents

    International Nuclear Information System (INIS)

    Hall, E.J.; Miller, R.C.; Osmak, R.; Zimmerman, M.

    1982-01-01

    An established line of mouse fibroblasts (10T1/2 cells) cultured in vitro was used to compare the incidence of oncogenic transformation produced by x rays, the hypoxic cell radiosensitizer misonidazole, and a range of commonly used chemotherapy agents. A 3-day exposure to misonidazole at a concentration obtainable during treatment produced an incidence of transformation similar to that of about 50 rad. When chemotherapy agents were tested at concentrations comparable to those used clinically and matched to produce similar cell killing, the incidence of transformation varied widely: some agents, such as vincristine, did not produce transformation at a level detectable above background, while others, such as cis-plantinum, appear to be potent carcinogens and produce transformation at a rate orders of magnitude higher than that achieved with x rays

  13. Metabolism and radiosensitization of 4,5-dimethylmisonidazole, a ring-substituted analog of misonidazole

    International Nuclear Information System (INIS)

    Born, J.L.; Smith, B.R.; Harper, N.; Koch, C.J.

    1992-01-01

    In the present study, methyl groups were added to the imidazole ring of misonidazole in order to hinder adduct formation with cellular molecules after reductive-activation of the compound. It was anticipated that this would substantially decrease the hypoxic-cell toxicity of the parent drug. The presence of the two methyl groups reduced the half-wave reduction potential of dimethyl misonidazole (DMM) by about 70 mV, so we expected that its radiosensitizing ability would also decrease. In direct comparison with misonidazole, DMM, at equimolar concentrations, showed dramatically reduced binding to cellular macromolecules under bioreductive conditions, both in vivo, using a liver perfusion system, and in vitro, using tissue culture cells incubated under extreme hypoxia. However, DMM was only moderately less toxic than the parent compound, and showed greatly diminished radiation sensitization capacity. Since the decrease in toxicity was much less than expected, and the decrease in radiosensitization was much more than expected, this compound may be an important drug for continuing studies on the mechanisms of radiation sensitization, binding and cytotoxicity caused by electron affinic drugs. (Author)

  14. A controlled trial of misonidazole in the curative treatment of infiltrating bladder cancer

    International Nuclear Information System (INIS)

    Bydder, P.V.; Burry, A.F.; Gowland, S.; Bourne, R.G.; Chapman, P.; Firth, L.A.; Gray, A.J.; McIlroy, R.

    1989-01-01

    Between 1980 and 1983 a total of 89 patients with infiltrating transitional cell carcinoma of the bladder were entered into a multi centre randomised controlled clinical trial with either misonidazole or placebo added to the first 40.00 Gy of radiotherapy. Depending on their referring clinician, patients then completed treatment with either further radiotherapy to a radical dose, or surgery four weeks later. All patients have been followed up for a minimum of three years, and no significant difference has been found in local control, survival, or pathological downstaging of the tumour. The neurotoxicity was considerable, with 43% of patients receiving misonidazole developing a peripheral neuropathy, starting five weeks on average after beginning treatment, and with a mean duration of 27 months. Eighty per cent of patients affected still had peripheral neuropathy at three years or their prior death. There is a suggestion that alcohol may predispose to the neuropathy. This study failed to show any benefit of misonidazole in tumour control and produced unacceptably high levels of toxicity. 14 refs., 8 figs., 9 tabs

  15. The Rise and Fall of Metronidazole for Clostridium difficile Infection.

    Science.gov (United States)

    Chahine, Elias B

    2018-06-01

    Clostridium difficile is posing urgent health threats. Older studies have shown that metronidazole and vancomycin are equally effective in the treatment of Clostridium difficile infection (CDI). Given its inexpensive cost and low propensity to select antimicrobial resistant organisms, metronidazole became rapidly the drug of choice despite its pharmacokinetic limitations in the treatment of CDI. However, newer studies demonstrated that metronidazole is inferior to vancomycin, prompting clinicians to change their long-standing position on using metronidazole for mild to moderate infections and on reserving vancomycin for severe infections. Moving forward, metronidazole will fall out of favor in the treatment of CDI.

  16. Physical and Release Properties of Metronidazole Suppositories ...

    African Journals Online (AJOL)

    80, sodium salicylate and methylcellulose as adjuvants. The setting time, solidification point and melting range of the suppositories were determined, along with their crushing strength, disintegration time and the time for 80% of metronidazole to be released from the suppositories (t80). Results: The ranking of setting time for ...

  17. Clinical evaluation of misonidazole combined with radiotherapy in the treatment of carcinoma of the esophagus. A double-blind randomized trial

    Energy Technology Data Exchange (ETDEWEB)

    Irie, Goro (Hokkaido Univ., Sapporo (Japan). School of Medicine); Sakurai, Tomoyasu; Kikuchi, Yuzo

    1984-10-01

    A double-blind trial of misonidazole in esophageal cancer was undertaken from January 1981 to October 1982 as collaborative effort of the department of radiology of 18 institutions. The purposes of this study were: (1) To establish whether misonidazole can increase the effect of radiation in the treatment of patients with inoperable esophageal cancer and (2) to assess the toxic effects of misonidazole. A total 119 patients were enrolled in this study and 104 (misonidazole group : 48 patients, control group : 56 patients) were determined as eligible for evaluation. The patients were randomly allocated into two groups receiving either misonidazole or placebo. The patients were irradiated with 2 Gy/fraction, 5 times a week to a total dose of 40--75 Gy (mostly 60 Gy). 0.5g/m/sup 2/ of misonidazole was given 4 hours before each radiotherapy up to 10g/m/sup 2/. The effect of the treatment was evaluated as a decrease in the volume of the tumors. Histological types of the tumors were squamous cell carcinoma except a case with adenocarcinoma. The distribution of patients according to the stage and tumor type on X-ray images was equivalent in both groups. 85.4% of the patients in the misonidazole group obtained a complete response (CR) or a partial response (PR) as compared to 83.9% in the control group. No difference was demonstrated in the tumor regression comparing the two groups. Four patients in the misonidazole group (8%) developed central or peripheral neuropathy. There have been no severe complications in any of the patients. This study has failed to demonstrate any advantage for the addition of misonidazole in the radiation therapy of esophageal cancer. Possible reasons for the failure to demonstrate any therapeutic gain from misonidazole were discussed.

  18. Enhancement of radiation response of SqII mouse tumors by combined treatment with misonidazole, vidarabine, and ACNU

    International Nuclear Information System (INIS)

    Asakura, Hideo; Akita, Yuzo; Kosaka, Noboru; Majima, Hideyuki; Suzuki, Norio.

    1987-01-01

    It is well known that misonidazole (Miso.) is a hypoxic cell sensitizer, vidarabine (Ara-A) is a PLD repair inhibitor, and ACNU is an anticancer drug derivative of nitrosourea. The effect of combined use of these drugs and radiation was studied. SqII tumor, an anaplastic squamous cell carcinoma was transplanted to the right thighs of WHT male mice. At 9 days after transplantation, the tumors of about 600 mm 3 were treated by several protocols. After the treatment, tumor growth curves were drawn and the time required to reach twice the initial volume of the treatment was determined. The results were as follows. The combination of 3 agents, Miso., Ara-A, and radiation was the most effective, followed by that of Miso., ACNU, and radiation, which was better than another combination of Miso. and radiation. The effect of Ara-A, ACNU and radiation was inferior to Miso. and radiation. The effect of Miso., Ara-A and ACNU was further inferior to radiation alone. The combination of 4 agents, Miso., Ara-A, ACNU and radiation was effective in the same degree or slightly inferior to Miso., Ara-A and radiation. On the other hand, effect of combined treatment with drugs and radiation without Miso. was not so remarkable on this mouse tumor, in other words, Miso. played the most important role among these 3 drugs. This study showed that the combination of Miso., Ara-A and radiation was the most effective among these tested and may be useful for the clinical control of cancer. Furthermore, this combination did not include anticancer drugs which cause bone marrow suppression and intestinal disorders. (author)

  19. Enhancement of radiation response of SqII mouse tumors by combined treatment with misonidazole, vidarabine, and ACNU

    Energy Technology Data Exchange (ETDEWEB)

    Asakura, Hideo; Akita, Yuzo; Kosaka, Noboru; Majima, Hideyuki; Suzuki, Norio

    1987-01-01

    It is well known that misonidazole (Miso.) is a hypoxic cell sensitizer, vidarabine (Ara-A) is a PLD repair inhibitor, and ACNU is an anticancer drug derivative of nitrosourea. The effect of combined use of these drugs and radiation was studied. SqII tumor, an anaplastic squamous cell carcinoma was transplanted to the right thighs of WHT male mice. At 9 days after transplantation, the tumors of about 600 mm/sup 3/ were treated by several protocols. After the treatment, tumor growth curves were drawn and the time required to reach twice the initial volume of the treatment was determined. The results were as follows. The combination of 3 agents, Miso., Ara-A, and radiation was the most effective, followed by that of Miso., ACNU, and radiation, which was better than another combination of Miso. and radiation. The effect of Ara-A, ACNU and radiation was inferior to Miso. and radiation. The effect of Miso., Ara-A and ACNU was further inferior to radiation alone. The combination of 4 agents, Miso., Ara-A, ACNU and radiation was effective in the same degree or slightly inferior to Miso., Ara-A and radiation. On the other hand, effect of combined treatment with drugs and radiation without Miso. was not so remarkable on this mouse tumor, in other words, Miso. played the most important role among these 3 drugs. This study showed that the combination of Miso., Ara-A and radiation was the most effective among these tested and may be useful for the clinical control of cancer. Furthermore, this combination did not include anticancer drugs which cause bone marrow suppression and intestinal disorders.

  20. Intravaginal metronidazole gel versus metronidazole plus nystatin ovules for bacterial vaginosis: a randomized controlled trial.

    Science.gov (United States)

    Sanchez, Sixto; Garcia, Patricia J; Thomas, Katherine K; Catlin, Mary; Holmes, King K

    2004-12-01

    We compared metronidazole 0.75% gel (containing 37.5 mg metronidazole per dose) with ovules containing metronidazole 500 mg and nystatin 100,000 U, for intravaginal treatment of bacterial vaginosis (BV). In a single-blinded trial, symptomatic women with BV by both Amsel and Nugent criteria were randomly assigned to gel or ovules, once nightly for 5 nights, and asked to return 3 times after treatment. Analyses were intent-to-treat. Of 151 women with BV by both criteria at enrollment, 138 (91%) returned at least once. Product limit estimates for persistence or recurrence of BV at 14, 42, and 104 days were 20% (95% CI 10%-29%), 38% (95% CI 25%-48%), and 52% (95% CI 37%-63%) after gel treatment, and 4% (95% CI 0%-9%), 17% (95% CI 7%-26%), and 33% (95% CI 21%-46%) after ovule treatment ( P = .01). Among women without BV at first follow-up, subsequent intercourse without condoms independently predicted subsequent recurrence ( P Metronidazole/nystatin ovules were significantly more effective than metronidazole gel. Unprotected sex predicted recurrence after initial improvement.

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

    Science.gov (United States)

    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.

  2. Metronidazole-induced encephalopathy in a patient with liver cirrhosis.

    Science.gov (United States)

    Cheong, Hyeong Cheol; Jeong, Taek Geun; Cho, Young Bum; Yang, Bong Joon; Kim, Tae Hyeon; Kim, Haak Cheoul; Cho, Eun-Young

    2011-06-01

    Encephalopathy is a disorder characterized by altered brain function, which can be attributed to various causes. Encephalopathy associated with metronidazole administration occurs rarely and depends on the cumulative metronidazole dose, and most patients with this condition recover rapidly after discontinuation of therapy. Because metronidazole is metabolized in the liver and can be transported by the cerebrospinal fluid and cross the blood-brain barrier, it may induce encephalopathy even at a low cumulative dose in patients with hepatic dysfunction. We experienced a patient who showed ataxic gait and dysarthric speech after receiving metronidazole for the treatment of hepatic encephalopathy that was not controlled by the administration of lactulose. The patient was diagnosed as metronidazole-induced encephalopathy, and stopping drug administration resulted in a complete recovery from encephalopathy. This case shows that caution should be exercised when administering metronidazole because even a low dose can induce encephalopathy in patients with liver cirrhosis.

  3. Metronidazole resistance in Campylobacter jejuni from poultry meat

    DEFF Research Database (Denmark)

    Andersen, Sigrid Rita; Shukri, Naseer Mahmoud; Boel, Jeppe

    2006-01-01

    The occurrence of metronidazole resistance was investigated among Campylobacter jejuni in raw poultry meat collected from supermarkets. MICs were determined by the agar dilution procedure in the testing range of 3 to 60 mu g/ml metronidazole. The MICs showed a bimodal distribution with a signific......The occurrence of metronidazole resistance was investigated among Campylobacter jejuni in raw poultry meat collected from supermarkets. MICs were determined by the agar dilution procedure in the testing range of 3 to 60 mu g/ml metronidazole. The MICs showed a bimodal distribution...

  4. Effects of oxygen and misonidazole on cell transformation and cell killing in C3H 10T1/2 cells by X rays in vitro

    International Nuclear Information System (INIS)

    Borsa, J.; Sargent, M.D.; Einspenner, M.; Azzam, E.I.; Raaphorst, G.P.

    1984-01-01

    The effects of oxygen (air) and misonidazole on the transformation and killing of 10T1/2 cells by X rays were examined. The oxygen effect for the cell transformation end point was very similar to that for cell killing. Misonidazole enhanced both cell killing and cell transformation to a similar extent. The enhancement of both end points by misonidazole occurred only in the absence of oxygen during irradiation and was of lesser magnitude than that observed for oxygen. These results demonstrate that the radiation chemical processes leading to cell killing and cell transformation, respectively, are affected similarly by these two enhancers of radiation action. 22 references, 3 figures, 2 tables

  5. Study of the effect of misonidazole in conjunction with radiotherapy for the treatment of head and neck cancer

    Energy Technology Data Exchange (ETDEWEB)

    Henk, J.M.; Adams, G.E.; Ash, D. (Medical Research Council, London (UK))

    1984-07-01

    The effect of the hypoxic cell sensitiser misonidazole as an adjuvant to radiotherapy of head and neck cancer was tested in a randomised double blind study. Patients with squamous carcinoma of the upper alimentary and respiratory tract, excluding those with early disease with good prognosis, who were deemed suitable for radical radiotherapy and fit to receive the drug were entered. Two radiotherapy regimes were employed, 10 fractions in 3 weeks to a modal tumour dose of 4000-4500 cGy, and 20 fractions in 4 weeks to a modal tumour dose of 5000-5750 cGy. Participating radiotherapists opted for one of the schemes. Misonidazole or placebo capsules were administered 4 to 5 hours before each fraction of radiotherapy to a total of 11 to 13 g/m/sup 2/. 168 patients were treated with 10 fractions and 99 with 20 fractions, between March 1979 and November 1981, when entry was stopped because of the high incidence of drug toxicity and lack of benefit. The estimated hazard ratio for local control was 0.89, indicating a slight advantage to misonidazole, statistically insignificant (p = 0.5). Peripheral neuropathy occurred in 56 patients receiving misonidazole, and was more severe when treatment was given in 10 fractions.

  6. New Analytical Method for the Determination of Metronidazole in ...

    African Journals Online (AJOL)

    New Analytical Method for the Determination of Metronidazole in Human Plasma: Application to Bioequivalence Study. ... Methods: Metronidazole was extracted from human plasma through one step of ... http://dx.doi.org/10.4314/tjpr.v11i5.14.

  7. Mechanism and clinical significance of metronidazole resistance in Helicobacter pylori

    NARCIS (Netherlands)

    van der Wouden, EJ; Thijs, JC; Kusters, JG; van Zwet, AA; Kleibeuker, JH

    2001-01-01

    Metronidazole was introduced in 1959 for the treatment of Trichomonas vaginalis, but was subsequently shown to be active against anaerobic and some micro-aerophilic bacteria as well. In anaerobic microorganisms with their low redox potential, metronidazole is reduced to its active metabolite by a

  8. Chemical radiosensitizers with special reference to metronidazole

    International Nuclear Information System (INIS)

    Sharma, R.; Purohit, O.P.; Nair, C.R.; Dutta, T.K.

    1982-01-01

    An attempt at rationalisation of drug dose schedule for a radiosensitizer in a cancer clinic is attempted. A prospective analysis of tissue tolerance, response data and complications of the two groups of patients (treated by oral and high intermittent rectal routes) was made with matched control. The study group has definite use of metronidazole. It is further highlighted that there is an additional advantage of the rectal administration route of the drug as compared to that of the oral route. This is a preliminary communication. (author)

  9. The effect of dexamethasone on the radiation survival response and misonidazole-induced hypoxic-cell cytotoxicity in Chinese hamster cells V-79-753B in vitro

    International Nuclear Information System (INIS)

    Millar, B.C.; Jinks, S.

    1981-01-01

    Overnight exposure of Chinese hamster cells, V-79-753B, to microgram quantities of the synthetic corticosteroid, dexamethasone, resulted in a decrease in sensitivity towards radiation, both in air and in hypoxia. The effect was dose-modifying and the oxygen enhancement ratio did not change appreciably. Similarly, when dexamethasone-treated hypoxic cells were irradiated in the presence of misonidazole, a hypoxic cell radiosensitizer, there was a decrease in radiation sensitivity compared with untreated hypoxic cells irradiated with misonidazole. (author)

  10. Reversible metronidazole-induced neurotoxicity after 10 weeks of therapy.

    Science.gov (United States)

    AlDhaleei, Wafa; AlMarzooqi, Ayesha; Gaber, Nouran

    2018-04-20

    Metronidazole is a commonly used antimicrobial worldwide. The most common side effects that have been reported are nausea, vomiting and hypersensitivity reactions. However, neurotoxicity has been reported with the use of metronidazole but rather rare. The most common neurological manifestation is peripheral neuropathy involvement in the form of sensory loss. It is worth mentioning that central neurotoxicity is a rare side effect of metronidazole use but reversible. The manifestations vary from a headache, altered mental status to focal neurological deficits. The diagnosis is mainly by neuroimaging in the setting of acute neurological change in the patient status. Here, we report a case of metronidazole-induced neurotoxicity in a 38-year-old male patient who was admitted with a brain abscess and was started on metronidazole for more than 10 weeks. © BMJ Publishing Group Ltd (unless otherwise stated in the text of the article) 2018. All rights reserved. No commercial use is permitted unless otherwise expressly granted.

  11. Optimizing the time interval between administration of misonidazole and irradiation: an in vitro study

    International Nuclear Information System (INIS)

    Hall, E.J.; Astor, M.

    1982-01-01

    When misonidazole is used in clinical radiotherapy it is common practice to irradiate 4 hours after oral administration, when drug concentration has reached a maximum in the tumor. If irradiation were further delayed, the drug concentration would decrease due to drug excretion, and the effective radiosensitizing ability of the remaining drug would increase. This paper describes experiments in which V79 cells, cultured in vitro, were used to simulate the in vivo situation and investigate the effect of prolonged preincubation prior to irradiation for a range of simulated drug half-lives. The results indicate that, when drug concentration decays exponentially with a 4 hour half-life, the same amount of radiosensitization is obtained whether the radiation is delivered immediately after the addition of the drug or if it is delayed for 4-1/2 hours

  12. Managing trichomonal vaginitis refractory to conventional treatment with metronidazole.

    OpenAIRE

    Ahmed-Jushuf, I H; Murray, A E; McKeown, J

    1988-01-01

    Three patients with vulvovaginitis caused by Trichomonas vaginalis, which was refractory to conventional treatment with metronidazole are described. The T vaginalis strain isolated from one patient was resistant to metronidazole (minimum inhibitory concentration (MIC) more than 100 mg/l) under aerobic conditions, although under anaerobic conditions it was as susceptible as a normal reference strain. The effect of the concomitant use of other medication and the influence of other vaginal patho...

  13. Metronidazole combined with nystatin (vagitories) in the prevention of bacterial vaginosis after initial treatment with oral metronidazole.

    Science.gov (United States)

    Pulkkinen, P; Saranen, M; Kaaja, R

    1993-01-01

    In a double-blind trial comprising 66 patients we assessed the effect of metronidazole-nystatin vagitories on the prevention of bacterial vaginosis (BV) in women using IUD as a contraceptive method after an initial oral single dose of 2.0 g metronidazole and 7 days of intravaginal metronidazole-nystatin or placebo treatment. The prophylactic treatment consisted of metronidazole-nystatin or placebo vagitories applied at bedtime for 3 days after menstruation over 6 consecutive menstrual periods. The patients were randomized in two study groups: a treatment group of 32 patients (group A) and a placebo group of 34 patients (group B). The overall objective cure rate after the initial treatment was 97% in group A and 91% in group B. After 6 months of follow-up, the overall cumulative objective cure rate in group A was 100%, and 76% in group B. The single-dose oral treatment was well tolerated and no notable side effects were recorded.

  14. Role of the rdxA and frxA genes in oxygen-dependent metronidazole resistance of Helicobacter pylori

    NARCIS (Netherlands)

    M.M. Gerrits (Monique); E.J. van der Wouden; D.A. Bax (Dorine); A.A. van Zwet (Anton); A.H.M. van Vliet (Arnoud); J.G. Kusters (Johannes); J.C. Thijs; E.J. Kuipers (Ernst); A. de Jong (Albertine)

    2004-01-01

    textabstractAlmost 50 % of all Helicobacter pylori isolates are resistant to metronidazole, which reduces the efficacy of metronidazole-containing regimens, but does not make them completely ineffective. This discrepancy between in vitro metronidazole resistance and treatment

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

    Science.gov (United States)

    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

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

    Science.gov (United States)

    Kumari, Mrinalini; Singh, Poonam

    2015-01-01

    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. 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. 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. The fruit extract of TT ameliorates the MTZ-induced alterations in the testis.

  17. Radiation and misonidazole in children with brain stem gliomas and supratentorial glioblastoma

    International Nuclear Information System (INIS)

    Bloom, H.J.G.; Bugden, R.D.

    1982-01-01

    In a series of 484 children with intracranial tumors referred to the Royal Marsden Hospital for radiotherapy, there were 47 (12%) examples of inoperable pontine and medullary tumors for which the 5-year survival rate was 17%. The limited local tumor mass in brain stem tumors, the absence of cerebro-spinal or distant metastases, and their often initial good but short-lived response to irradiation, all support the trial of a chemical radiosensitizing agent with which to try and achieve greater and more prolonged local control of the disease. Since the prognosis for cerebral hemisphere glioblastoma, which is relatively uncommon in children, is also extremely poor, such cases were included in this pilot study. The problems and possible risks associated with combined radiotherapy and a chemical radiosensitizer in children with brain tumors is discussed. So far, 8 children with brain stem tumors and 3 children with cerebral hemisphere gliomas heave been treated in this study. In addtion, data is also available on 3 children re-treated for incurrent medulloblastomas. Preliminary observations regarding experience with this small series will be reported including blood misonidazole levels, drug tolerance and the possible influence of anticonvulsants and steriods on toxicity

  18. Misonidazole as a radiosensitizer in the radiotherapy of glioblastomas and oesophageal cancer. Pharmacokinetic and clinical studies

    International Nuclear Information System (INIS)

    Tamulevicius, P.; Streffer, C.; Bamberg, M.; Scherer, E.

    1981-01-01

    Since May 1978 the hypoxic-cell radiosensitizer, misonidazole (MIS), has been under clinical investigation in a phase III trial with multiple doses of the drug in 11 patients with brain tumours (seven glioblastomas, four recurrent brain tumours) and three patients with oesophageal carcinoma. The doses of MIS administered were usually well tolerated but the principal toxicities observed were peripheral neuropathy as well as nausea and vomiting in the glioblastoma patients. The neuropathy was completely reversible. The incidence of neuropathy was not related to the pharmacological parameters of plasma level or half-life. Pharmacological assessment by high-pressure liquid chromatography included assays of plasma, urine and cerebrospinal fluid. The demethylated product, Ro-05-9963, was detected as the major metabolite. Peak plasma levels were obtained one to four hours after administration of MIS, with a half-life of five to ten hours. Cerebrospinal fluid levels of MIS correlated well with those of the plasma. MIS was mainly excreted as the demethylated metabolite, but less than 40% of the given dose could be recovered. The results obtained suggest that the present MIS dosage for glioblastoma patients results in a low plasma level with no observable therapeutic effect. (author)

  19. Experience in the radical radiotherapy of cancer in the bilharzial bladder: the use of misonidazole

    International Nuclear Information System (INIS)

    Awwad, H.K.; Akhoush, H.; El-Merzabani, M.; El Badawy, S.; Barsoum, M.; Abd El Baki, H.

    1984-01-01

    The results of application of a protracted split-course radiotherapy regimen in T 3 carcinoma in the bilharzial bladder are presented. A total dose of 70 Gy spread over 61 days was divided into four courses separated by gaps of 1, 2 and 1 week, respectively. Each of the first three sessions comprised eight fractions, 2.5 Gy each, while four such fractions were given during the fourth course. Patients were randomized between radiotherapy alone (32 patients) and radiotherapy plus misonidazole (MIS) (30 patients). The drug was given in a daily oral dose of 0.5 g/m 2 , 3.5 h prior to each radiation treatment. The treatment was well tolerated and MIS did not augment the radiation reaction. Mild or moderate peripheral neuropathy was experienced by 63% of patients of the group. Age and degree of upper obstructive uropathy were the most important determinants of the risk of neuropathy. The 2-year disease-free actuarial survival rates amounted to 58% and 44% in the MIS and radiotherapy alone groups respectively; the difference is not significant. The results were significantly better in case of transitional cell (67%) than squamous cell cancer (29%) but were independent of the histological grade. A strong correlation was found between the magnitude of tumour volume reduction after 40 Gy and the long-term end results. (Auth.)

  20. Glutathione requirement for the rejoining of radiation-induced DNA breaks in misonidazole-treated cells

    International Nuclear Information System (INIS)

    Edgren, M.; Revesz, L.

    1985-01-01

    The role of glutathione (GSH) in the rejoining of radiation-induced single-strand DNA breaks (ssb) was studied in human fibroblast cultures sensitized to radiation by a 30 min treatment with 1 mM misonidazole (MISO). Hypoxically irradiated cells, deficient in GSH, either inherently, or due to a 16 h incubation with 1 mM buthionine sulphoximine (BSO), rejoined the breaks after MISO treatment at a lower rate and to a lesser extent than did GSH-proficient cells. Without MISO treatment, the hypoxically induced ssb were rejoined in the GSH-deficient cells as effectively as in the proficient cells. It is concluded that a large proportion of the breaks which arise after hypoxic irradiation in the presence of MISO are of a different type to those which arise in the absence of the drug, and require a particular GSH-dependent, enzymatic repair system. This requirement for rejoining in hypoxically irradiated, MISO-treated cells is similar to that seen earlier in MISO-untreated, oxically irradiated cells, and suggests that the ssb induced by radiation in the presence of MISO or oxygen are of a similar nature. (author)

  1. Experience in the radical radiotherapy of cancer in the bilharzial bladder: the use of misonidazole

    Energy Technology Data Exchange (ETDEWEB)

    Awwad, H.K.; Akhoush, H.; El-Merzabani, M.; El Badawy, S.; Barsoum, M.; Abd El Baki, H. (National Cancer Institute, Cairo (Egypt). Radiotherapy Dept.)

    1984-06-01

    The results of application of a protracted split-course radiotherapy regimen in T/sub 3/ carcinoma in the bilharzial bladder are presented. A total dose of 70 Gy spread over 61 days was divided into four courses separated by gaps of 1, 2 and 1 week, respectively. Each of the first three sessions comprised eight fractions, 2.5 Gy each, while four such fractions were given during the fourth course. Patients were randomized between radiotherapy alone (32 patients) and radiotherapy plus misonidazole (MIS) (30 patients). The drug was given in a daily oral dose of 0.5 g/m/sup 2/, 3.5 h prior to each radiation treatment. The treatment was well tolerated and MIS did not augment the radiation reaction. Mild or moderate peripheral neuropathy was experienced by 63% of patients of the group. Age and degree of upper obstructive uropathy were the most important determinants of the risk of neuropathy. The 2-year disease-free actuarial survival rates amounted to 58% and 44% in the MIS and radiotherapy alone groups respectively; the difference is not significant. The results were significantly better in case of transitional cell (67%) than squamous cell cancer (29%) but were independent of the histological grade. A strong correlation was found between the magnitude of tumour volume reduction after 40 Gy and the long-term end results.

  2. Enhancement of nitrosourea cytotoxicity by misonidazole in vitro: correlation with carbamoylating potential.

    Science.gov (United States)

    Mulcahy, R. T.; Dembs, N. L.; Ublacker, G. A.

    1984-01-01

    We have investigated the relationships between nitrosourea structure and physicochemical properties and the ability of misonidazole (MISO) to potentiate nitrosourea cytotoxicity in an in vitro model system. EMT-6/Ro tumour cells were exposed in suspension to each of 9 different nitrosourea anti-tumour drugs under hypoxic and aerobic culture conditions. Additional cultures were similarly treated with nitrosoureas in the presence of 1.0 mM MISO. Seven of the 9 nitrosoureas did not demonstrate any selective toxicity toward aerobic or hypoxic cells. In contrast, chlorozotocin (CHLZ) was slightly more toxic toward hypoxic cells while Bis-OH CyNU more effectively killed aerobic cells. The addition of MISO to the drug treatment enhanced the effectiveness of all the nitrosoureas under hypoxic conditions, with the exception of CHLZ which was uninfluenced by MISO. The magnitude of the MISO dose enhancement factor (DEF, defined as the ratio of drug doses required to reduce cell survival to S = 10(-3) in 4 hours in the absence and presence of 1.0 mM MISO) for each combination was examined as a function of the relative carbamoylating or alkylating activity of the nitrosourea included in that combination. Such an analysis revealed a significant (P less than 0.05) positive correlation between relative carbamoylating potency and DEF. No significant (P greater than 0.20) relationship could be established for DEF and alkylating activity. PMID:6704305

  3. Effects of glutathione depletion by buthionine sulfoximine on radiosensitization by oxygen and misonidazole in vitro

    International Nuclear Information System (INIS)

    Shrieve, D.C.; Denekamp, J.; Minchinton, A.I.

    1985-01-01

    Buthionine sulfoximine (BSO) has been used to deplete glutathione (GSH) in V79-379A cells in vitro, and the effect on the efficiency of oxygen and misonidazole (MISO) as radiosensitizers has been determined. Treatment with 50 or 500 μM BSO caused a rapid decline in GSH content to less than 5% of control values after 10 hr of exposure. Removal of BSO resulted in a rapid regeneration of GSH after 50 μM BSO, but little regeneration was observed over the subsequent 10-hr period after 500 μM. Cells irradiated in monolayer on glass had an oxygen enhancement ratio (OER) of 3.1. After 10-14 hr pretreatment with 50 μM BSO, washed cells were radiosensitized by GSH depletion at all oxygen tensions tested. The OER was reduced to 2.6, due to greater radiosensitization of hypoxic cells than aerated ones by GSH depletion. In similar experiments performed with MISO, an enhancement ratio of 2.0 could be achieved with 0.2 mM MISO in anoxic BSO-pretreated cells, compared to 2.7 mM MISO in non-BSO-treated cells. These apparent increases in radiosensitizer efficiency in GSH-depleted cells could be explained on the basis of radiosensitization of hypoxic cells by GSH depletion alone. These results are consistent with hypoxic cell radiosensitization by GSH depletion and by MISO or oxygen acting by separate mechanisms

  4. Pharmacokinetics of paracetamol in chicks treated with metronidazole

    Directory of Open Access Journals (Sweden)

    S.M. Hussain

    2017-06-01

    Full Text Available Effect of metronidazole on the pharmacokinetics of paracetamol were examined in chicks. Chicks were dosed orally with metronidazole at 350 mg\\kg of body weight daily (10 -13 days of age. On the last day of metronidazole dosing, chicks injected intraperitoneally with paracetamol at of 50 mg\\kg of body weight. Paracetamol appeared in chick plasma at 52.00, 45.00, 40.75, 32.75, 23.25 µg \\ml after 0.25, 0.50, 0.75, 1, 2, 4 hours of injection respectively. A significantly decreased the concentration paracetamol at times of 0.25, 0.50, 0.75, 1, 4 hours post injection and appeared at concentrations of 36.62, 35.37, 25.62, 20.50, 11.00 µg\\ml. These was reflected by changes in the pharmacokinetics of paracetamol as show by the increase elimination rate constant (48% and decrease in the half-life (32 % and increase in volume distribution (29% and increase in clearance by (96% and decrease in the area under the plasma curve (33% and decrease in the area under moment curve 65% and lack mean residence time (33%. These results indicate that oral dosing of chicks with metronidazole for four consecutive days and this effect increase in the elemination rate of paracetamol and this effect must be considered when therapy with paracetamol when given during metronidazole therapy.

  5. Metronidazole pharmacokinetics in patients with acute renal failure.

    Science.gov (United States)

    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.

  6. Irradiation with misonidazole and hyperbaric oxygen: final report on a randomized trial in advanced head and neck cancer

    International Nuclear Information System (INIS)

    Sealy, R.; Cridland, S.; Barry, L.; Norris, R.

    1986-01-01

    One hundred and thirty patients with locally advanced squamous carcinoma of the head and neck were treated in a prospective randomized trial to compare conventional irradiation (63.00 Gy in 30 fractions) with a combination sensitizer regimen of misonidazole and hyperbaric oxygen. The drug (2.0 gm/m2) was given with each of six fractions of 6.0 Gy in hyperbaric oxygen at 3 ATA. The results support a previous study and favor the combination at 1 year at better than the 10% level. This regimen could be useful for bulky primary or nodal disease

  7. Therapeutic Efficacy Evaluation of Metronidazole and Some ...

    African Journals Online (AJOL)

    Erah

    million new human cases arise every year, and at least 350 ... Leishmania burdens in different mouse tissues. This is ... parasite load in mice infected with L. major .... LC PCR development ..... Medicine," McGraw-Hill, New York, 1984; p. 443.

  8. Cellular uptake of misonidazole and analogues with acidic or basic functions

    International Nuclear Information System (INIS)

    Dennis, M.F.; Stratford, M.R.L.; Wardman, P.; Watts, M.E.

    1985-01-01

    Average intracellular concentrations of five radiosensitizers in hamster fibroblast-like V79-379A cells in vitro were measured by high performance liquid chromatography, varying the extracellular pH(pHsub(e)) and estimating the apparent intracellular pH from the distribution of 5,5-dimethyloxazolidine-2,4-dione. The intracellular: extracellular concentration ratio for the 2-nitroimidazole, misonidazole was constant at about 0.7 for pHsub(e)=6.6-7.6, whereas the weak base, Ro 03-8799 (1-(2-nitro-1-imidazolyl)-3-N-piperidino-2-propanol) was concentrated intracellularly at pHsub(e)=7.3-7.4 by a factor of 3.3, the factor increasing from about 0.8 at pHsub(e)=6.0, to 7.5 at pHsub(e)=7.85. The weak acid, azomycin (2-nitroimidazole) showed approximately constant uptake (factor 1.1) between pHsub(e)=6.0-7.0, decreasing to 0.8 at pHsub(e)=7.3 and 0.4 at pHsub(e)=7.8. Measurements of intracellular uptake of Ro 31-0052 (the more hydrophilic and less basic 3'-hydroxypiperidino analogue of Ro 03-8799) and of Ro 31-0258 (3-(2-nitro-1-imidazolyl)propionic acid, a stronger acid than azomycin) were made for comparison. The results were compared with theoretical calculations of pH-induced concentration gradients; the time dependence of the uptake of the bases is not at present clearly understood. (author)

  9. Radiotherapy in combination with misonidazole and ACNU (1-(4 amino-2 methyl-5 pyrimidinyl) methyl-3-(2 chloroethyl)-3-nitrosourea hydrochloride)

    Energy Technology Data Exchange (ETDEWEB)

    Asakura, Hideo; Mashima, Yasuoki; Kanazawa, Atsuko (Toranomon Hospital, Tokyo (Japan)); Maruhashi, Akira

    1983-11-01

    Misonidazole and ACNU were intermittently combined one or several times with radiotherapy. Misonidazole was orally administered with a dose of 1.5g/m/sup 2/ 4 hours before irradiation. ACNU with a dose of 60mg/m/sup 2/ mixed with predonisolone (40 mg) was intravenously injected between misonidazole and irradiation. Irradiation was carried out with the fractionation of 120 rads per fraction and 5 fractions per week in lung cancer and of 200 rads per fraction and 3 fractions per week in head and neck cancer. Twenty lung cancer patients and 13 head and neck cancer patients were treated from July, 1980 to April, 1982. In lung cancer, BAI (bronchial artery infusion) of adriamycin was added besides the above-mentioned treatment. Complete plus partial response rate of lung cancer was 85%, one year survival rate by Kaplan-Meier's method 65 +- 10.7% and two year survival rate 39.8 +- 12.2%, which were promising. In head and neck cancer, complete plus partial response rate was 76.9%, and one year survival rate 67.3 +- 13.6%. Head and neck cancer contained many recurrent and many advanced stage cases. Side effects of this treatment were nausea, vomiting and thrombocytopenia due to ACNU. These were all transient. Any peripheral neuropathy due to misonidazole was not observed in this treatment scheme. The fractionation in multomodality therapy is discussed and the mechanism of chemosensitization is bibliographically discussed.

  10. Failure of misonidazole-sensitized radiotherapy to impact upon outcome among stage III-IV squamous cancers of the head and neck

    International Nuclear Information System (INIS)

    Fazekas, J.; Pajak, T.F.; Wasserman, T.; Marcial, V.; Davis, L.; Kramer, S.; Rotman, M.; Stetz, J.

    1987-01-01

    As part of the RTOG research effort in the treatment of advanced, inoperable squamous cancer of the head and neck region, the hypoxic cell sensitizer, misonidazole, was selected for investigation as an adjuvant to definitive irradiation. Based upon a pilot experience (78-02) showing a 67% complete response rate among 36 AJC Stage III-IV patients receiving full-dose irradiation and 6 weekly p.o. doses of misonidazole, a phase III trial was carried out from '79-'83. Three hundred and six patients were entered, 42% of whom had oropharyngeal primaries and with 78% of all cases representing T3 or T4 (inoperable) lesions. Only 16% of the entire series presented with N0 necks. Fractionation was altered among the misonidazole-receiving patients, in contrast to standard 5 treatments per week among control patients, such that 2 separate treatments were given on each day of p.o. misonidazole administration (2.0 gm/m2/wk X 6 doses, 2.5 Gy in a.m., 2.1 Gy in p.m.). Total tumor doses were identical among the two treatment arms except that a limitation of 40.0 Gy to spinal cord was specified for sensitized radiotherapy vs. 45.0 Gy for control patients. Primary tumor clearance was observed to be 55-60%, with minor variations according to tumor stage and site. The local regional control rate among radiotherapy-alone patients was 26% at 2 years compared to 22% (2 years) within the misonidazole-receiving group. Analysis of survival revealed no advantage to the sensitized patients, with 55 +/- 2% surviving 1 year and 22 +/- 1% living 3 years following treatment in both treatment categories. Distant metastases as first site of failure (12-13%) and the local failure among initial complete responders (46%) showed no advantage to the misonidazole group. Although a misonidazole dosage of 2.0 gm/m2/wk X 6 (12 gm/m2 total) is well tolerated, no clinical benefit was demonstrated in this randomized trial

  11. Survival curves of irradiated glutathione-deficient human fibroblasts: indication of a reduced enhancement of radiosensitivity by oxygen and misonidazole

    International Nuclear Information System (INIS)

    Midander, J.; Deschavanne, P.J.; Malaise, E.P.; Revesz, L.

    1982-01-01

    Fibroblasts derived from a patient with 5-oxoprolinuria are genetically deficient in glutathione synthetase. This deficiency causes a dramatic decrease in intracellular glutathione (GSH) level. The radiosensitivity of GSH deficient cells (GSH) was studied in vitro using colony forming ability as an endpoint. Cells with normal GSH level, obtained from the healthy brother of the patient, were used as controls. When irradiated in 95% air-5% CO 2 , GSH - cells are slightly but significantly more radiosensitive than GSH + controls (dose modifying factor (DMF) of 1.2). When irradiated in argon, the survival curve of GSH - cells indicates an oxygen enhancement ratio (OER) of 1.5 when compared to the curve obtained in oxic conditions. The OER of control cells in the same conditions is 2.9. In comparison to results obtained in air, 100% oxygen moderately increases the radiosensitivity of GSH + cells (DMF 1,23), while it has a very low effect on GSH - cells (DMF 1.06). These results suggest that intracellular GSH plays an essential protective role in hypoxia, its effect is reduced in air and practically disappears in 100% oxygen. When cells are incubated with 8 mM misonidazole 2 hours before irradiation, the drug has a much greater sensitizing effect on GSH + cells (DMF 2.33) than on GSH - cells (DMF 1.55). The results demonstrate that intracellular GSH level plays a major role in the response of hypoxic cells, irradiated either alone or in the presence of misonidazole

  12. Delivery of metronidazole from purified Nigerian sheabutter in ...

    African Journals Online (AJOL)

    The drug release capacity of SO was significantly improved by incorporation of a surfactant (cetrimide). MTZ in sheabutter ointment exhibited intermediate drug release values (0.73 mg min-½ , 9.30%), which were neither enhanced by hydration nor by the surfactant. Key Words: Metronidazole, Sheabutter, Ointment Bases, ...

  13. Absence of sensitization of reversions in yeast by metronidazole

    International Nuclear Information System (INIS)

    Krishnan, D.; Singh, D.R.; Mahajan, J.M.; Madhvanath, U.

    1977-01-01

    Metronidazole (Flagyl; 2-methyl-5-nitroimidazole-1-ethanol) is of potential clinical application as a radiosensitizer. Studies have been made of the effect of 1mM metronidazole on γ-induced heteroallelic recombination (reversion) under euoxic or hypoxic conditions in yeast strain BZ34, and compared with the effect on survival. The o.e.r. for reversions was 2.2, and very close to that for survival (2.3), indicating that oxygen equally sensitized gross cellular events such as killing, and genetic phenomena like reversions. The introduction of metronidazole during irradiation sensitized cells with killing as the end point only in hypoxic condition, whereas with reversion as the end point no sensitization due to the chemical was observed either in euoxic or hypoxic conditions. Since DNA damage is responsible for both cell-killing and mutations, the sensitizer might have been expected to have had an equal effect on both these end-points. The results show that only in a limited sense can metronidazole be considered to be an oxygen mimic. (U.K.)

  14. Degradation kinetics of metronidazole and its mutual prodrug with ...

    African Journals Online (AJOL)

    Dr Renu Chadha

    degradation of the drug and prodrug as a function of concentration, pH and temperature. In terms of enthalpy of ... Keywords: Calorimetry, stability studies, degradation kinetics, ciprofloxacin, metronidazole. ... action of ciprofloxacin to form a broad spectrum ...... Stability testing of pharmaceutical by isothermal heat conduction.

  15. Possibilities of the reduction of a dose of metronidazole during irradiation of tumor with subsequent induced hyperglycemia

    International Nuclear Information System (INIS)

    Vinskaya, N.P.; Voloshina, E.A.; Kozin, S.V.

    1989-01-01

    The therapeutic efficacy of a scheme of polyradiomodification with metronidazole (MZ) administration was investigated in experiments on mice with Ehrlich carcinoma before local irradiation of tumors and with subsequent induced hyperglycemia (IH) depending on a MZ dose. For equally effective potentiation of the effect of radiation on a tumor during a combined use of MZ and postradiation IH a 4-fold lower dose of the drug was required as combined to MZ used alone. The combined effect of the modifiers was superadditive. The use of IH in this scheme not only potentiated skin radiation reactions on a tumor growth zone but also slighly weakened their expression

  16. Misonidazole and unconventional radiation in advanced squamous cell carcinoma of the esophagus: a phase II study of the Radiation Therapy Oncology Group

    International Nuclear Information System (INIS)

    Ydrach, A.A.; Marcial, V.A.; Parsons, J.; Concannon, J.; Asbell, S.O.; George, F.

    1982-01-01

    This is a report on Radiation Therapy Oncology Group (RTOG) Protocol78-32, a Phase I/II prospective study aimed at determining tolerance, tumor response, and survival of squamous cell carcinoma of the esophagus treated with unorthodox fractionation radiotherapy combined with misonidazole. Misonidazole was administered by mouth 4 to 6 hr prior to radiation, at a dose of 1.0 to 1.25 Gm/.m 2 ; blood levels were measured at about 4 hr after intake of the drug and reported in micrograms/ml. Radiotherapy was administered at 4 to 6 hr post-misonidazole dose and given with 400 rad fractions, alternating 2 or 3 times/week, up to 4,800 rad. A total of 43 patients were entered; 26 are evaluated for survival at 1 year post accession. Thirty patients (88%) received the planned radiation course. Twenty-eight patients (78%) received the planned misonidazole dosage. Tumor response, evaluated in 18 patients, showed a complete regression (C.R.) in only 2 patients (11%); and partial response (P.R.) in 6 patients (33%). Eight patients (44%) showed no tumor response to planned therapy. Toxicity was acceptable and in 38 evaluated patients only 4 reported (11%) nausea and vomiting, 7 reported mild paresthesias (18%). The median survival was only five months. In 26 patients evaluated for 1 year survival determination, only 1 survived (3.8%) this period. In view of the poor tumor response and low survival observed, we do not recommend that this particular fractionation regimen with misonidazole be used in a Phase III randomized trial in squamous cell carcinoma of the esophagus

  17. Value of adjuvant misonidazole in the definitive irradiation of advanced head and neck squamous cancer: an RTOG pilot study (78-02)

    International Nuclear Information System (INIS)

    Fazekas, J.T.; Goodman, R.L.; McLean, C.J.

    1981-01-01

    This RTOG Phase II trial was instituted to determine the toxicity and potential value of the electron-affinic agent, Misonidazole, adjunctive to definitive radiotherapy of T3 and T4 squamous cancers of the oral cavity, oropharynx, or hypopharynx. The fractionation schema was altered to deliver two separate treatments (250 rad and 210 rad) on each day when Misonidazole was administered, while maintaining relatively ''standard'' fractionation (5 fractions and 1000 rad per week). In order to achieve effective enhancement while minimizing toxicity, Misonidazole doses were limited to 2.5 gm/m 2 once per week, not to exceed 24 gm total cumulative in 6 weeks. The dosage was reduced to 2.0 gm/m 2 /wk after the first 30 patients were entered. Among the 50 patients entered, toxicity was confined to the nervous system, with one-third of the patients experiencing mild or moderate peripheral neuropathies and an equal number developing nausea and/or vomiting following p.o. drug administration. Encephalopathy occurred in 10% of the 30 patients receiving 2.5 mg/m 2 dosage. Serum drug levels and cumulative Misonidazole doses did not correlate well with toxicity or response except in comparison of the ''no response'' to the ''complete response'' categories. Immediate mucosal and skin reactions were not enhanced and unusual late normal tissue effects were not encountered. Complete disappearance of all visible and palpable primary tumor was noted in 67% of the 36 patients who completed the adjuvant sensitizer program. Tumor response and survival did not generally correlate with measured (serum) Misonidazole concentration; recurrence was also independent of these measured levels. These preliminary results seemed sufficiently encouraging to warrant a Phase III (randomized) study, now underway by the RTOG

  18. Value of adjuvant misonidazole in the definitive irradiation of advanced head and neck squamous cancer: an RTOG pilot study (number78-02)

    International Nuclear Information System (INIS)

    Fazekas, J.T.; Goodman, R.L.; McLean, C.J.

    1981-01-01

    This RTOG Phase II trial was instituted to determine the toxicity and potential value of the electron-affinic agent, Misonidazole, adjunctive to definitive radiotherapy of T3 and T4 squamous cancers of the oral cavity, oropharynx, or hypopharynx. The fractionation schema was altered to deliver two separate treatments (250 rad and 210 rad) on each day when Misonidazole was administered, while maintaining relatively ''standard'' fractionation (5 fractions and 1000 rad per week). In order to achieve effective enhancement while minimizing toxicity, Misonidazole doses were limited to 2.5 gm/m 2 once per week, not to exceed 24 gm total cumulative in 6 weeks. Definitive radiation therapy in the range of 6500-7000 rad was delivered over 6 1/2-8 weeks. The dosage was reduced to 1.0 gm/m 2 /wk after the first 30 patients were entered. Among the 50 patients entered, toxicity was confined to the nervous system, with one-third of the patients experiencing mild or moderate peripheral neuropathies (paresthesias, numbness) and an equal number developing nausea and/or vomiting following p.o. drug administration. Encelphalopathy occurred in 10% of the 30 patients receiving 2.5 mg/m 2 dosage. Serum drug levels and cumulative Misonidazole doses did not correlate well with toxicity or response except in comparison of the ''no response'' to the ''complete response'' categories. Immediate mucosal and skin reactions were not enhanced and unusual late normal tissue effects were not encountered. Complete disappearance of all visible and palpable primary tumor was noted in 67% of the 36 patients who completed the adjuvant sensitizer program. Tumor response and survival did not generally correlate with measured (serum) Misonidazole concentration; recurrence was also independent of these measured levels

  19. The aerobic activity of metronidazole against anaerobic bacteria.

    Science.gov (United States)

    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. Copyright © 2015 Elsevier B.V. and the International Society of Chemotherapy. All rights reserved.

  20. A case of metronidazole-resistant Trichomonas vaginalis in pregnancy.

    Science.gov (United States)

    Forbes, Georgina L; Drayton, Rachel; Forbes, Gavin D

    2016-09-01

    Trichomonas vaginalis is a sexually transmitted protozoan infection resulting in vulvo-vaginitis and altered vaginal discharge in symptomatic women. Trichomoniasis has been implicated in causing adverse pregnancy outcomes such as low birth weight and pre-term labour. Metronidazole is the recommended first-line treatment 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 re-infection, although metronidazole resistance has previously been documented. Antimicrobial susceptibility testing for T. vaginalis is currently not available in the UK. Patients with disease unresponsive to first-line treatments pose a major challenge, as therapeutic options are limited. We present the case of a patient with presumed resistant infection during pregnancy, and the additional treatment issues that this presented. © The Author(s) 2015.

  1. Stevens-Johnson syndrome following use of metronidazole in a dental patient.

    Science.gov (United States)

    Mazumdar, Goutameswar; Shome, Koushik

    2014-01-01

    Metronidazole alone rarely causes Stevens-Johnson syndrome (SJS). We present a case of an elderly male patient who, following metronidazole use, developed neurological symptoms followed by pain and blisters on both soles, erythema of face and neck, scrotal itching and erosion, and hemorrhagic encrustation around the lips and oral mucous membrane. Initial neurological symptoms followed by mucocutaneous manifestation of SJS following metronidazole use is probably a new presentation of this case.

  2. Intensification of the antitumoral effect of ionizing radiations in combined use of metronidazole and hyperglycemia

    International Nuclear Information System (INIS)

    Vinskaya, N.P.; Voloshina, E.A.; Vygodskaya, A.L.; Yarmonenko, S.P.

    1984-01-01

    The authors have shown that a more pronounced antitumor effect of radiation in the combined use of metronidazole and induced short-term hyperglycemia (STH) may result not only from the summation of the two effects: the sensitizing effect of metronidazole and decreased viability of irradiated cells caused by STH but also from the intensified cytotoxic effect of metronidazole on hypoxic tumor cells. It was also noted that when hypoxic cells subjected to the sensitizing effect of electron acceptor sensitizers are found in the normal (skin) and tumorous tissues, STH use following irradiation in the presence of metronidazole enchances selectively the tumor radiation effect

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

    International Nuclear Information System (INIS)

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

    1990-01-01

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

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

    Science.gov (United States)

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

    2014-01-01

    Chronic periodontitis is a multifactorial infectious disease associated with Gram-negative strict anaerobes which are immersed in the subgingival biofilm. Porphyromonas gingivalis, an important periodontal pathogen, is frequently detected in patients with chronic periodontitis. Although isolates of P. gingivalis tend to be susceptible to most antimicrobial agents, relatively little information is available on its in vitro antimicrobial susceptibility. The aim of this study was to determine the frequency of P. gingivalis in patients with chronic periodontitis and to assess antimicrobial susceptibility in terms of minimum inhibitory concentration (MIC) of clinical isolates to metronidazole and tetracycline. A descriptive, observational study was performed including 87 patients with chronic periodontitis. Samples were taken from the periodontal pocket using paper points, which were placed in thioglycollate broth. Samples were incubated for 4 hours at 37°C in anaerobic conditions and finally replated on Wilkins-Chalgren anaerobic agar (Oxoid). Bacteria were identified using the RapIDTMANAII system (Remel) and antimicrobial susceptibility was determined with the M.I.C. Evaluator test (MICE, Oxoid). P. gingivalis was identified in 30 of the 87 patients with chronic periodontitis, which represents a frequency of 34.5%. All 30 isolates (100%) were sensitive to metronidazole, with MIC values ranging from 0015-4ug/ml. Regarding tetracycline, 27 isolates (90%) were sensitive, with MIC values ranging from periodontitis between the group of patients with chronic periodontitis and P. gingivalis and the group of patients with chronic periodontitis without P. gingivalis. In conclusion, P. gingivalis was found at a frequency of 34.5% in patients with chronic periodontitis and clinical isolates were highly sensitive to metronidazole and tetracycline.

  5. Release and diffusional modeling of metronidazole lipid matrices.

    Science.gov (United States)

    Ozyazici, Mine; Gökçe, Evren H; Ertan, Gökhan

    2006-07-01

    In this study, the first aim was to investigate the swelling and relaxation properties of lipid matrix on diffusional exponent (n). The second aim was to determine the desired release profile of metronidazole lipid matrix tablets. We prepared metronidazole lipid matrix granules using Carnauba wax, Beeswax, Stearic acid, Cutina HR, Precirol ATO 5, and Compritol ATO 888 by hot fusion method and pressed the tablets of these granules. In vitro release test was performed using a standard USP dissolution apparatus I (basket method) with a stirring rate of 100 rpm at 37 degrees C in 900 ml of 0.1 N hydrochloric acid, adjusted to pH 1.2, as medium for the formulations' screening. Hardness, diameter-height ratio, friability, and swelling ratio were determined. Target release profile of metronidazole was also drawn. Stearic acid showed the highest and Carnauba wax showed the lowest release rates in all formulations used. Swelling ratios were calculated after the dissolution of tablets as 9.24%, 6.03%, 1.74%, and 1.07% for Cutina HR, Beeswax, Precirol ATO 5, and Compritol ATO 888, respectively. There was erosion in Stearic acid, but neither erosion nor swelling in Carnauba wax, was detected. According to the power law analysis, the diffusion mechanism was expressed as pure Fickian for Stearic acid and Carnauba wax and the coupling of Fickian and relaxation contributions for other Cutina HR, Beeswax, Compritol ATO 888, and Precirol ATO 5 tablets. It was found that Beeswax (kd=2.13) has a very close drug release rate with the target profile (kt=1.95). Our results suggested that swelling and relaxation properties of lipid matrices should be examined together for a correct evaluation on drug diffusion mechanism of insoluble matrices.

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

    Science.gov (United States)

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

    2015-10-01

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

  7. Potentiation of the action of metronidazole on Helicobacter pylori by omeprazole and bismuth subcitrate

    DEFF Research Database (Denmark)

    Andersen, L P; Colding, H; Kristiansen, J E

    2000-01-01

    test (Etest). With 0.5 MIC of either of the two drugs, the susceptibility of all H. pylori4 mg/l) reverted to being metronidazole sensitive. These results suggested that either bismuth salts or proton pump inhibitors may be effective in the treatment of some infections with metronidazole-resistant H...... to regimens that include proton pump inhibitors. In the present study, the synergistic effect of subinhibitory concentrations (0.25-0.5 MIC) of either bismuth subcitrate or omeprazole with metronidazole on the susceptibility of 42 H. pylori strains was investigated by agar dilution method and the Epsilometer......Treatment failures using triple therapy that include metronidazole, are common in patients infected with metronidazole-resistant Helicobacter pylori in the gastric mucosa. Higher eradication rates in such patients have been described when treatment regimens include bismuth salts compared...

  8. The treatment of irradiated mice with polymicrobial infection caused by Bacteroides fragilis and Escherichia coli

    International Nuclear Information System (INIS)

    Brook, Itzhak; Ledney, G.D.

    1994-01-01

    The effects on the faecal flora and the efficacies of various antibiotic regimens administered as treatment for a mixed infection caused by Bacteroides fragilis and Escherichia coli in the irradiated host were investigated in a subcutaneous abscess model with C 3 H/HeN mice which had been exposed to 60 Co. The regimens used included imipenem, ofloxacin, metronidazole and the combination of ofloxacin and metronidazole. (author)

  9. The treatment of irradiated mice with polymicrobial infection caused by Bacteroides fragilis and Escherichia coli

    Energy Technology Data Exchange (ETDEWEB)

    Brook, Itzhak (Naval Medical Research Inst., Bethesda, MD (United States)); Ledney, G.D. (Armed Forces Radiobiology Research Inst., Bethesda, MD (United States))

    1994-02-01

    The effects on the faecal flora and the efficacies of various antibiotic regimens administered as treatment for a mixed infection caused by Bacteroides fragilis and Escherichia coli in the irradiated host were investigated in a subcutaneous abscess model with C[sub 3]H/HeN mice which had been exposed to [sup 60]Co. The regimens used included imipenem, ofloxacin, metronidazole and the combination of ofloxacin and metronidazole. (author).

  10. Gamma radiolysis of Cu(II) complex of metronidazole

    International Nuclear Information System (INIS)

    Mandal, P.C.; Bardhan, D.K.; Bhattacharyya, S.N.

    1990-01-01

    Aqueous solutions of Cu(II)Metronidazole (Cu(II)M) at neutral pH were irradiated with 60 Co γ-rays under different conditions of radiolysis. The radiolytic formation of HNO 2 and Cu(I) was followed. The radiolytic yields of chromophore loss of Cu(II)M were also determined under different conditions. The OH radicals attack the metal complex to give the OH adducts of the ligand at C 2 , C 4 , and C 5 either directly or through the formation of Cu(III) species. The C 5 -OH adduct, however, undergoes oxidative denitration and as a result the metal complex is decomposed. The OH adducts also undergo electron transfer to Cu(II) ion to give reduced complex. No denitration was observed due to the reaction of e eq - with the metal complex. On the other hand, the nitro group of the ligand in the complex undergoes successive 4-electron reduction to give hydroxylamino derivative. From the competition kinetics using t-butyl alcohol as the scavenger of OH in N 2 O saturated solution of the metal complex, the rate constant for the reaction of OH with complex was evaluated to be ca. 2.1x10 9 dm 3 mol -1 s -1 which is of the same order as that observed in the case of free metronidazole. (author)

  11. Rifaximin therapy for metronidazole-unresponsive Clostridium difficile infection: a prospective pilot trial.

    Science.gov (United States)

    Patrick Basu, P; Dinani, Amreen; Rayapudi, Krishna; Pacana, Tommy; Shah, Niraj James; Hampole, Hemant; Krishnaswamy, N V; Mohan, Vinod

    2010-07-01

    Clostridium difficile infection (CDI) is a recent epidemic in the United States, particularly in the hospital setting. Oral metronidazole is standard therapy for C. difficile infection, but resistance to metronidazole is becoming a clinical challenge. We evaluated the efficacy of the nonsystemic oral antibiotic rifaximin for the treatment of metronidazole-resistant C. difficile infection. Twenty-five patients with C. difficile infection were enrolled in the study. All had mild-to-moderate C. difficile infection (5-10 bowel movements a day without sepsis) unresponsive to metronidazole (i.e. stools positive for toxins A and B after oral metronidazole 500 mg three times daily [t.i.d.] for 5 days). After discontinuation of metronidazole, rifaximin 400 mg t.i.d. for 14 days was prescribed. Patients were followed for 56 days and stool was tested for C. difficile using polymerase chain reaction (PCR) to assess the effect of treatment. A negative PCR test result was interpreted as a favorable response to rifaximin. Sixteen of 22 patients (73%) were eligible for study inclusion and completed rifaximin therapy experienced eradication of infection (stool negative for C. difficile) immediately after rifaximin therapy and 56 days post-treatment. Three patients (12%) discontinued therapy because of abdominal distention. Rifaximin was generally well tolerated. In conclusion, rifaximin may be considered for treatment of mild-to-moderate C. difficile infection that is resistant to metronidazole. Larger randomized trials are needed to confirm these positive findings.

  12. Characterization of a stable, metronidazole-resistant Clostridium difficile clinical isolate.

    Directory of Open Access Journals (Sweden)

    Tarah Lynch

    Full Text Available BACKGROUND: Clostridium difficile are gram-positive, spore forming anaerobic bacteria that are the leading cause of healthcare-associated diarrhea, usually associated with antibiotic usage. Metronidazole is currently the first-line treatment for mild to moderate C. difficile diarrhea however recurrence occurs at rates of 15-35%. There are few reports of C. difficile metronidazole resistance in the literature, and when observed, the phenotype has been transient and lost after storage or exposure of the bacteria to freeze/thaw cycles. Owing to the unstable nature of the resistance phenotype in the laboratory, clinical significance and understanding of the resistance mechanisms is lacking. METHODOLOGY/PRINCIPAL FINDINGS: Genotypic and phenotypic characterization was performed on a metronidazole resistant clinical isolate of C. difficile. Whole-genome sequencing was used to identify potential genetic contributions to the phenotypic variation observed with molecular and bacteriological techniques. Phenotypic observations of the metronidazole resistant strain revealed aberrant growth in broth and elongated cell morphology relative to a metronidazole-susceptible, wild type NAP1 strain. Comparative genomic analysis revealed single nucleotide polymorphism (SNP level variation within genes affecting core metabolic pathways such as electron transport, iron utilization and energy production. CONCLUSIONS/SIGNIFICANCE: This is the first characterization of stable, metronidazole resistance in a C. difficile isolate. The study provides an in-depth genomic and phenotypic analysis of this strain and provides a foundation for future studies to elucidate mechanisms conferring metronidazole resistance in C. difficile that have not been previously described.

  13. Association of Metronidazole with Cancer: A Potential Risk Factor or Inconsistent Deductions?

    Science.gov (United States)

    Adil, Muhammad; Iqbal, Waheed; Adnan, Fazal; Wazir, Shabnam; Khan, Imran; Khayam, Mohammad Umar; Kamal, Mohammad Amjad; Ahmad, Shafiq; Ahmad, Jawad; Khan, Ishaq N

    2018-03-29

    Metronidazole is a synthetic derivative of nitroimidazole that has been widely used for the treatment of several bacterial and protozoal parasitic infections including trichomoniasis, amoebiasis, giardiasis, liver abscess, acute ulcerative gingivitis, syphilis and tropical phagedena. In addition to its toxicity in the gastrointestinal tract and central/peripheral nervous system, metronidazole has been reported to cause mucosal imbalance by affecting the expression of mucin (Muc2 gene), which is responsible to form an insoluble mucous barrier that protects the gut lumen from microbial colonization. Since metronidazole is a nitro-group containing compound and used significantly for therapeutic purposes, scientists evaluated its carcinogenicity in different preclinical in-vitro and in-vivo studies. In addition to the preclinical in-vitro validation of DNA damage, metronidazole has been reported to induce cancer in the variety of animal models including lung cancer, malignant lymphomas, breast cancer, hepatocellular carcinoma, pituitary tumors, testicular neoplasms and uterine cancer. Several retrospective cohort studies have reported metronidazole as a potential risk factor for lung cancer (n = 771), cervical cancer (n = 2500), breast cancer (n = 2), cholangiocarcinoma (n = 1), and neuroblastoma (n = 28). So far, all the reported data have confirmed metronidazole carcinogenicity in animals; however, it is still controversial in humans. Based on previous observations, the oxidative metabolites from metronidazole metabolism are shown to have more carcinogenic effects than the parent drug itself. Since ~40% of drug metabolism is reliant on cytochromes, the inter-patient' differences in metronidazole metabolism potentially indicate the individual susceptibility to developing cancer. Due to these potent carcinogenic behaviors, use of metronidazole for animals treatment and its uses in animal food products are barred in the USA and European countries; however, its clinical

  14. Metronidazole-Induced Encephalopathy in Alcoholic Liver Disease: A Diagnostic and Therapeutic Challenge.

    Science.gov (United States)

    Sonthalia, Nikhil; Pawar, Sunil V; Mohite, Ashok R; Jain, Samit S; Surude, Ravindra G; Rathi, Pravin M; Contractor, Qais

    2016-10-01

    Acute encephalopathy in a patient with alcoholic liver disease (ALD) is a commonly encountered emergency situation occurring most frequently due to liver failure precipitated by varying etiologies. Acute reversible cerebellar ataxia with confusion secondary to prolonged metronidazole use has been reported rarely as a cause of encephalopathy in patients with ALD. We describe a decompensated ALD patient with recurrent pyogenic cholangitis associated with hepatolithiasis who presented to the emergency department with sudden-onset cerebellar ataxia with dysarthria and mental confusion after prolonged use of metronidazole. Magnetic resonance imaging (MRI) of the brain was suggestive of bilateral dentate nuclei hyper intensities on T2 and fluid-attenuated inversion recovery sections seen classically in metronidazole-induced encephalopathy (MIE). Decompensated liver cirrhosis resulted in decreased hepatic clearance and increased cerebrospinal fluid concentration of metronidazole leading to toxicity at a relatively low total cumulative dose of 22 g. Both the clinical symptoms and MRI brain changes were reversed at 7 days and 6 weeks, respectively, after discontinuation of metronidazole. WHY SHOULD AN EMERGENCY PHYSICIAN BE AWARE OF THIS?: A patient with ALD presenting with encephalopathy creates a diagnostic dilemma for the emergency physician regarding whether to continue metronidazole and treat for hepatic encephalopathy or to suspect for MIE and withhold the drug. Failure to timely discontinue metronidazole may worsen the associated hepatic encephalopathy in these patients. Liver cirrhosis patients have higher mean concentration of metronidazole and its metabolite in the blood, making it necessary to keep the cumulative dose of metronidazole to < 20 g in them. Copyright © 2016 Elsevier Inc. All rights reserved.

  15. [Investigation of in vitro metronidazole resistance in the clinical isolates of Trichomonas vaginalis].

    Science.gov (United States)

    Ertabaklar, Hatice; Yaman Karadam, Senem; Malatyalı, Erdoğan; Ertuğ, Sema

    2016-10-01

    Trichomonas vaginalis, a flagellated, urogenital anaerobic protozoon is reported as an important cause of vaginitis with a global distribution. Although metronidazole is the primary choice of drug for the treatment of trichomoniasis, the presence of resistant isolates from many different countries highlights the need of novel drugs for the treatment. Many studies from Turkey mostly dealing with the in vitro effects of compounds and natural products against T.vaginalis have been reported, however, only one study has been encountered searching the metronidazole resistance in a single T.vaginalis isolate. The aim of this study was to determine the in vitro metronidazole resistance and minimum lethal concentrations (MLCs) of the isolates from symptomatic cases. T.vaginalis strains isolated from vaginal discharge samples of symptomatic women that were sent to Adnan Menderes University Faculty of Medicine, Research and Training Hospital Parasitology Laboratory, between 2009-2014 period, were included in the study. The strains were isolated by the inoculation of samples into trypticase-yeast-maltose medium supplemented with 10% fetal calf serum. A total of 40 T.vaginalis isolates stored by cryopreservation were revived before the experiments. T.vaginalis trophozoites were incubated with different concentrations of metronidazole (200, 100, 50, 25, 12.5, 6.25, 3.12, 1.56 μg/ml) and the viability of cells were examined in both aerobic and anaerobic conditions under phase contrast microscope. Additionally, non-motile isolates were further inoculated into fresh media and viability was checked. The wells containing motile trophozoites after 48 hours of incubation with 15 µg/ml and/or higher metronidazole concentration in anaerobic condition and 75 µg/ml and/or higher metronidazole concentration in aerobic conditions were determined as resistant isolates. Of the 40 T.vaginalis isolates three (7.5%) were resistant to metronidazole. MLC mean values of metronidazole

  16. Palliation of advanced pelvic malignant disease with large fraction pelvic radiation and misonidazole: final report of RTOG phase I/II study

    International Nuclear Information System (INIS)

    Spanos, W.J. Jr.; Wasserman, T.; Meoz, R.; Sala, J.; Kong, J.; Stetz, J.

    1987-01-01

    Between October 1979 and June 1982 forty-six patients were entered on a non-randomized Phase I-II protocol for the evaluation of Misonidazole combined with high dose per fraction radiation for the treatment of advanced pelvic malignancies. Pelvic radiation consisted of 1000 cGy in one fraction repeated at 4-week intervals for a total of three treatments. Oral Misonidazole at a dose of 4 gm/m2 was administered 4-6 hr prior to radiation (total dose 12 g/m2). The distribution of histology consisted of 20 gynecologic, 24 bowel, and 2 prostate malignancies. Of the thirty-seven patients completing the three treatments; there were 6 complete responses (14% CR), 10 partial responses (27% PR) 19 minimal or no response (32% NR), and 4 unevaluable. One patient remains NED 5.5 years following radiation. Toxicity directly related to Misonidazole was minimal and consisted primarily of transcient Grade 1, 2 peripheral neuropathy (20% Grade 1, 4% Grade 2) and Grade 2 ototoxicity (4%). Radiation toxicity was significant for late bowel damage. There were 4 (11%) Grade 3 and 7 (19%) Grade 4 gastro-intestinal (GI) toxicities. Kaplan-Meier plot of GI toxicity showed a progressive increase in incidence with time for projected rate of 49% Grade 3, 4 by 12-month. GI toxicity (Grade 3, 4) was also related to tumor response. The complication rate was 80% (4/6) for CR, 30% (3/10) for PR and 26% (5/19) for NR or progression. Because of the GI complication rate, this protocol for palliation of advanced pelvic malignancies has been replaced by a protocol that uses 4 fractions over 2 days (b.i.d.) of 370 cGy per fraction repeated at 3-week intervals for a total of 3 courses

  17. Intraoperative radiotherapy in combination with misonidazole. In special reference to the drug concentration in tumors and normal tissues and to the initial effect of the treatment

    Energy Technology Data Exchange (ETDEWEB)

    Takahashi, Masaji; Ono, Kouji; Hamanaka, Daizaburo; Dodo, Yoshihiro; Hiraoka, Masahiro [Kyoto Univ. (Japan). Faculty of Medicine

    1983-03-01

    A hypoxic cell radiosensitizer, misonidazole, was applied to 28 patients with carcinoma who received intraoperative radiotherapy. A single dose of 2-3g/m/sup 2/ of the drug was given orally to each patient three hours prior to the start of general anesthesia. The levels of misonidazole and its metabolite, desmethylmisonidazole, in blood, tumors and normal tissues taken from excised materials were measured by a high performance liquid chromatography. The results showed that the concentration levels of misonidazole and desmethylmisonidazole in blood correlated neither to oral doses of 2-3g/m/sup 2/ nor to the function of time after drug ingestion until eight hours. The mean value of blood levels was 77.1 +- 10.9..mu..g/ml. A wide range of 10-96% of the blood level was found in tumors. High levels were observed in gastric cancer and brain tumor (glioblastoma) but not in colorectal cancer and osteosarcoma. It was, however, likely that the concentrations in tumors depended on tumor sizes and/or necrotic areas rather than histologic types and/or sites of tumors. It was also noted that the concentration in normal tissues ranged widely from 11 to 87% of the blood level. Higher concentrations showing more than 75% were found in the ulnar nerve, the stomach and the skin. However, 3 of 4 materials for the stomach and 2 of 3 materials for the skin showed low levels of less than 30% and less than 22% respectively. In 27 of 28 cases different doses of 28-50 Gy with different energies of electrons were delivered intraoperatively. It is impossible so far to derive conclusive results of this study, really because of the short period of observation following the treatment.

  18. Helicobacter pylori resistance to metronidazole and clarithromycin in Ireland.

    LENUS (Irish Health Repository)

    O'connor, Anthony

    2012-02-01

    INTRODUCTION: Helicobacter pylori eradication rates have fallen considerably in recent years. Antibiotic resistance is thought to be rising. OBJECTIVES: To examine the levels of resistance to metronidazole (MTZ) and clarithromycin (CLA) in H. pylori, isolates were taken in a reference centre in Ireland from 2007 to 2008 and were compared to a similar cohort from a study in 1997. METHOD: Antimicrobial susceptibilities were tested by E-test. Frequencies of spontaneous metronidazole and clarithromycin resistance were measured on an agar plate containing the antibiotics at concentrations of 2x and 4x minimum inhibition concentration values. Clinical data were obtained from charts, laboratory and endoscopy reports. RESULTS: Two hundred and twenty-two patients were analyzed, 98 were females. Colonies amenable to culture were grown in 219 patients. Thirty-seven had prior attempts at eradication therapy (all with amoxicillin-CLA-proton pump inhibitor. A total of 31.5% of the patients had strains resistant to MTZ and 13.2% of the patients were noted to have strains resistant to CLA. About 8.6% of the patients had strains resistant to both the agents. CLA resistance was 9.3% in those who had no prior eradication therapy compared with 32.4% of those who had. CLA resistance increased from 3.9%, among treatment-naive patients in 1997, to 9.3% in our study. MTZ resistance was 29.1% in the treatment-naive population. In 1997, MTZ resistance in the treatment-naive cohort was 27.1%. MTZ resistance was more likely to occur in females (35.4 vs. 28.5%) than in males. CONCLUSION: This study shows that resistance to CLA among Irish patients infected with H. pylori has increased since 1997. The future of treatment may well lie in the widespread use of sensitivity testing before the treatment. This would promote an accurate treatment.

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

    Directory of Open Access Journals (Sweden)

    Mansoure Masoudi

    2017-02-01

    Full Text Available Objective: Due to the high incidence of bacterial vaginosis (BV and its resistance to chemical medications and considering the anti-bacterial and anti-fungal effects of Myrtus communis, the present study aimed to compare the therapeutic effects of the vaginal gel of M. communis 2% (in metronidazole base with metronidazole vaginal gel 0.75% alone on BV.Materials and Methods: This research was a random­ized controlled clinical trial conducted on 80 women of 18-40 years old with BV. Patients were divided into two groups of 40 women. Diagnostic criteria were Amsel's criteria and Gram staining. The first group received vaginal gel of metronidazole plus M. communis 2% and the second group received metronidazole vaginal gel alone for five consecutive nights. Therapeutic effects and Amsel’s criteria were assessed after one week. Finally, the data were analyzed by SPSS 16 using t-test and Chi square tests.Results: There was a significant difference in the therapeutic response between the two groups. The results demonstrated that the combination of metronidazole and M. communis had a higher efficiency (p

  20. Ensaio terapêutico na infecção por Giardia muris em camundongo com metronidazole, tinidazole, secnidazole e furazolidone

    Directory of Open Access Journals (Sweden)

    Claudia Cristina Pedigone Cruz

    1997-06-01

    Full Text Available Foi testado in vivo a sensibilidade de Giardia muris a quatro drogas comumente usadas no tratamento da giardíase humana. Foram utilizados 7 grupos de animais, com 12 camundongos cada, sendo que o grupo controle recebeu apenas solução salina 0,15M (0,5ml/animal. Os demais grupos receberam em dose única: metronidazole e furazolidone (500mg/kg, tinidazole e secnidazole (200mg/kg. A eficácia das drogas foi avaliada através da contagem de cistos nas fezes e pela ausência de trofozoítos no intestino. O metronidazole foi a droga mais eficaz. Os cortes histológicos mostraram diferenças entre o padrão da mucosa intestinal de animais normais e parasitados. No entanto, não se observou diferença entre o padrão de mucosa de animais infectados tratados e não tratados, o que sugere que estas alterações podem ser causadas pelo parasito e não pelas drogas.A comparative study about the effectiveness of metronidazole, tinidazole, secnidazole and furazolidone was performed on Giardia muris from mice naturally infected. Groups of 12 animals each was constituted: the control treated with saline; one treated with metronidazole; one treated with furazolidone; one treated with tinidazole; one treated with secnidazole; histological normal control; histological infected. Samples of three stools were examined before and after treatment with quantification of cysts. Animals were cured when the trophozoites was not seen in the small bowel. The curative activity of drugs was 58.3% for metronidazole, 50% for furazolidone, 40% for secnidazole and 16% for tinidazole. It was also showed that there was a different pattern of the intestinal mucosa from the control and infected groups, treated or not, suggesting that the alterations encountered in the mucosa of infected animals were due to the parasitism either the action of the drugs.

  1. Combined (radiation and surgery) treatment of laryngeal cancer patients using metronidazole

    International Nuclear Information System (INIS)

    Andreev, V.G.

    1985-01-01

    The results of combined treatment of 98 laryngeal cancer patients followed up for 1.5-3 years were analysed. Of them 68 received a preoperative radiotherapy course conbined with the metronidazole. The drug was given in the form of a sugar syrup suspension at a dose of 100-150 mg/kg 2.5-3 hours before irradiation, at 5 Gy twice a week reaching a summary focal dose of 20 Gy. Thirty patients received radiation therapy without metronidazole. Altogether 4 preoperative radiotherapy methods were used. An analysis of the results showed a significant improvement of the cure rates for laryngeal cancer patients using metronidazole. A better healing of postoperative wounds was noted. The author proved the appropriateness of preoperative irradiation by mean fractions up to a summary focal dose of 20 Gy combined with metronidazole and subsequent (on the last or next day of irradiation) radical operation

  2. Efficacy of tigecycline versus ceftriaxone plus metronidazole for the treatment of complicated intra-abdominal infections

    DEFF Research Database (Denmark)

    Qvist, Niels; Warren, Brian; Leister-Tebbe, Heidi

    2012-01-01

    This randomized, open-label, multi-center trial compared tigecycline (TGC), a broad-spectrum glycylcycline, with ceftriaxone-metronidazole (CTX/MET) for the treatment of complicated intra-abdominal infections (cIAI)....

  3. Effects of radiosensibilization by metronidazole on liver tissue in patients with gastric carcinomas

    International Nuclear Information System (INIS)

    D'yakova, A.M.; Stefani, N.V.; Zagrebin, V.M.; Senokosov, N.I.; Berdov, B.A.

    1985-01-01

    Metronidazole, used as radiosensitizer in preoperative radiotherapy of gastric carcinoma caused an increased glycogen accumulation in the left lobe of the liver with a radiation dose of 80-100 % of the isodose. The glycogen level was higher not only in comparison with the same liver area in patients without radiosensitizer but also with the right lobe of the own liver within in the area of stray radiation. The effect observed after radiation was considered as result of the sensitizing influence on liver tissue. The sensitizing effect of metronidazole depended on its concentration in the patient's serum. In the right lobe of the liver the glycogen level showed no alteration under metronidazole. Metronidazole reduced the activity of lactate dehydrogenase and cholinesterase in liver tissue independently of its concentration in the serum and of the radiation dose on particular parts of the liver. (author)

  4. Modification of the radiosensitizing effect of metronidazole by 5-fluorouracil and caffeine

    International Nuclear Information System (INIS)

    Esel'baeva, G.O.; Ermekova, S.A.

    1986-01-01

    A study was made of the combined effect of 5-fluorouracil, metronidazole, caffeine and radiation on radiosensitivity of Pliss lymphosarcoma and protein synthesis rate during the first few hours following irradiation. A complete regression of the tumor was noted in 100% of animals after a 3-fold exposure. Effective postirradiation inhibition of protein synthesis was achieved by injection of metronidazole and caffeine together with 5-fluorouracil

  5. Anti-anaerobic activity of levofloxacin alone and combined with clindamycin and metronidazole.

    Science.gov (United States)

    Credito, K L; Jacobs, M R; Appelbaum, P C

    2000-11-01

    Microdilution MICs of levofloxacin against twelve anaerobes ranged between 0.5-8.0 microg/ml and those of clindamycin and metronidazole between 0.008-2.0 and 0.25->16.0 microg/ml, respectively. Combination of levofloxacin with clindamycin and/or metronidazole in time-kill tests led to synergy at levofloxacin concentrations at or below the MIC in 7/12 strains.

  6. Sequential MR imaging (with diffusion-weighted imaging changes in metronidazole-induced encephalopathy

    Directory of Open Access Journals (Sweden)

    Rupinder Singh

    2017-01-01

    Full Text Available Metronidazole-induced neuro-toxicity, though rare, is known. A characteristic spatial distribution of lesions in cerebellar dentate nuclei and dorsal pons is known. However, temporal progression of lesions on magnetic resonance imaging (MRI has not been described previously. We describe two such cases which presented initially with splenial hyperintesity and showed progression to characterstic lesions. Both cases improved with stoppage of metronidazole.

  7. Clinical relevance of metronidazole and peripheral neuropathy: a systematic review of the literature.

    Science.gov (United States)

    Goolsby, Tiffany A; Jakeman, Bernadette; Gaynes, Robert P

    2018-03-01

    The objective of this paper was to review and evaluate the literature on metronidazole-associated peripheral neuropathy and determine the relevance in clinical practice. MEDLINE/PubMed, EBSCO, and Google Scholar were searched through February 2017 using the search terms metronidazole and peripheral neuropathy, or polyneuropathy, or paresthesia, or neurotoxicity. Relevant case reports, retrospective studies, surveys, and review articles were included. Bibliographies of all relevant articles were reviewed for additional sources. Overall, metronidazole is generally well tolerated, but serious neurotoxicity, including peripheral neuropathy, has been reported. The overall incidence of peripheral neuropathy associated with metronidazole is unknown. Our review found 36 case reports (40 unique patients) of metronidazole-associated peripheral neuropathy, with most cases (31/40) receiving a >42 g total (>4 weeks) of therapy. In addition, we reviewed 13 clinical studies and found varying rates of peripheral neuropathy from 0 to 50%. Within these clinical studies, we found a higher incidence of peripheral neuropathy in patients receiving >42 g total (>4 weeks) of metronidazole compared with those patients receiving ≤42 g total (17.9% vs. 1.7%). Nearly all patients had complete resolution of symptoms. In conclusion, peripheral neuropathy is rare in patients who receive ≤42 g total of metronidazole. Patients who receive higher total doses may be at higher risk of peripheral neuropathy, but symptoms resolve after discontinuation of therapy in most patients. Antimicrobial stewardship programs may consider use of antibiotic combinations that include metronidazole over broad-spectrum alternatives when treating with ≤42 g total of the drug (≤4 weeks). Published by Elsevier B.V.

  8. Are marketed topical metronidazole creams bioequivalent? Evaluation by in vivo microdialysis sampling and tape stripping methodology

    DEFF Research Database (Denmark)

    Garcia Ortiz, Patricia Elodia; Hansen, S H; Shah, Surendra P.

    2011-01-01

    To evaluate the bioequivalence of 3 marketed topical metronidazole formulations by simultaneous dermal microdialysis and stratum corneum sampling by the tape stripping methodology, and to compare the techniques as tools for the determination of bioequivalence.......To evaluate the bioequivalence of 3 marketed topical metronidazole formulations by simultaneous dermal microdialysis and stratum corneum sampling by the tape stripping methodology, and to compare the techniques as tools for the determination of bioequivalence....

  9. Anal submucosal injection: a new route for drug administration in pelvic malignancies. Part I. Experimental study of misonidazole distribution in serum and tissues, with special reference to urinary bladder. Preliminary report

    International Nuclear Information System (INIS)

    Shafik, A.; el-Merzabani, M.M.; el-Aaser, A.A.; el-Desouky, G.H.

    1986-01-01

    The anal and oral administration routes were compared in 30 rats to study the distribution of misonidazole, a radiation sensitizer, in the serum and tissues with special reference to the urinary bladder. 14C-labelled misonidazole was administered in a dose of 0.2 ml water/100 gm body weight containing 1 mu Ci misonidazole. The dose was given orally by stomach tube in 15 rats, and was injected in the submucosa of the anal canal in another 15. Animals were then killed after 15, 30, 60, or 120 minutes or after 24 hours. Organs were dissected, and radioactivity was determined in each by the internal standard method. The study has shown that the highest drug concentration in the bladder tissue relative to the serum was achieved with the anal submucosal route. Its level was eight and five times that of the serum 15 and 30 minutes after administration, respectively, in contrast to the oral route in which the drug concentration was one-quarter and equal to the serum level at the same time intervals. The anal route would thus provide the adequate channel required for misonidazole to promote radiation responsiveness in bladder carcinoma

  10. Potential of bisbenzimidazole-analogs toward metronidazole-resistant Trichomonas vaginalis isolates.

    Science.gov (United States)

    Korosh, Travis; Bujans, Emmanuel; Morada, Mary; Karaalioglu, Canan; Vanden Eynde, Jean Jacques; Mayence, Annie; Huang, Tien L; Yarlett, Nigel

    2017-10-01

    A bisoxyphenylene-bisbenzimidazole series with increasing aliphatic chain length (CH 2 to C 10 H 20 ) containing a meta- (m) or para (p)-benzimidazole linkage to the phenylene ring was tested for ability to inhibit the growth of metronidazole-susceptible (C1) and metronidazole-refractory (085) Trichomonas vaginalis isolates under aerobic and anaerobic conditions. Compound 3m, 2,2'-[α,ω-propanediylbis(oxy-1,3-phenylene)]bis-1H-benzimidazole, displayed a 5.5-fold lower minimum inhibitory concentration (MIC) toward T. vaginalis isolate 085 than metronidazole under aerobic growth conditions, (26 μm compared to 145 μm). A dose of 25 mg/kg per day for four days of compound 3m cured a subcutaneous mouse model infection using T. vaginalis isolates 286 (metronidazole susceptible) and 085 (metronidazole refractory). Compound 3m was weakly reduced by pyruvate:ferredoxin oxidoreductase, but unlike metronidazole was not dependent upon added ferredoxin. It is concluded from structure-activity relationships that there was no obvious trend based on the length of the central aliphatic chain, or the steric position of the bisbenzimidazole enabling prediction of biological activity. The compounds generally fulfill Lipinski's rile of five, indicating their potential as drug leads. © 2017 John Wiley & Sons A/S.

  11. The effect of iron on metronidazole activity against Trichomonas vaginalis in vitro.

    Science.gov (United States)

    Elwakil, Hala Salah; Tawfik, Rania Ayman; Alam-Eldin, Yosra Hussein; Nassar, Doaa Ashraf

    2017-11-01

    Metronidazole is administered in an inactive form then activated to its cytotoxic form within the hydrogenosome of trichomonads. Two hydrogenosomal proteins, pyruvate ferredoxin oxidoreductase (PFOR) and ferredoxin, play a critical role in the reductive activation of metronidazole. The expression of these proteins and other hydrogenosomal proteins are likewise positively regulated by iron. In the present study, the effect of iron on minimal lethal concentration (MLC) of metronidazole on in vitro cultured Trichomonas vaginalis(T. vaginalis) isolates was investigated. Interestingly, Addition of Ferrous ammonium sulphate (FAS) to T. vaginalis culture led to decrease in the MLC of metronidazole. On using aerobic assay, MLC of metronidazole on untreated T. vaginalis of both isolates was 12.5 μg/ml that decreased to 0.38 μg/ml on FAS treated trichomonads. Also anaerobic assay revealed that MLC on untreated parasites was 3.12 μg/ml that decreased to 0.097 μg/ml and 0.19 μg/ml for isolate 1 and isolate 2 respectively after iron addition. It was concluded that, addition of iron to in vitro cultured T. vaginalis decreases metronidazole MLC that was detected by both aerobic and anaerobic assays. Copyright © 2017 Elsevier Inc. All rights reserved.

  12. Metronidazole stewardship initiative at Christchurch hospitals-achievable with immediate benefits.

    Science.gov (United States)

    Gardiner, Sharon J; Metcalf, Sarah Cl; Chin, Paul Kl; Doogue, Matthew P; Dalton, Simon C; Chambers, Stephen T

    2018-04-13

    To evaluate an antimicrobial stewardship (AMS) initiative to change hospital prescribing practice for metronidazole. In October 2015, the Canterbury District Health Board (CDHB) AMS committee changed advice for metronidazole to promote two times daily dosing for most indications, prioritisation of the oral route and avoidance of double anaerobic cover. Adoption of the initiative was facilitated via change in prescribing guidelines, education and ongoing pharmacy support. Usage and expenditure on metronidazole for adult inpatients were compared for the five years pre- and two years post-change. Other district health boards (DHBs) were surveyed to determine their dosing recommendation for metronidazole IV. Mean annual metronidazole IV use, as defined daily doses per 1,000 occupied bed days, decreased by 43% post-initiative. Use of non-IV (oral or rectal) formulations increased by 104%. Total savings associated with the initiative were approximately $33,400 in drug costs plus $78,200 per annum in IV giving sets and post-dose flushes. Twelve of 20 (60%) DHBs (including CDHB) endorse twice daily IV dosing. In addition to financial savings, reduction in IV doses has potential benefits, including avoidance of IV catheter-associated complications such as bloodstream infections. Approaches to metronidazole dosing vary across DHBs and could benefit from national coordination.

  13. Functionality of innovative and generic celluloses in metronidazole formulations

    Directory of Open Access Journals (Sweden)

    Carmen Cristina Díaz Ramírez

    2011-03-01

    Full Text Available The wide variety of excipients available calls for evaluation of their functionality, in this case of the pharmaceutical performance of microcrystalline celluloses and sodium cross-linked carboxymethylcelluloses from different sources. This evaluation includes parameters such as powder flow, compactibility, ejection pressure and dissolution from fast-release tablets as well as from floating granules and controlled-release tablets. In a previous study, the excipient Carmacel® presented better disintegration properties compared to Croscarmellose®. However, the evaluation showed better compactibility performance for Croscarmellose®. These characteristics were observed using pure excipients. Nevertheless, these advantages have not been confirmed in tests employing immediate-release or modified-release formulations containing metronidazole. Regarding microcrystalline celluloses, the present comparative evaluation between pure Alfacel ® types 101 and 102 and pure Avicel® types 101 and 102 showed better compactibility performance for the latter. However, for metronidazole formulations, this advantage was not evident in the innovative excipient. Notwithstanding, this study revealed better compactibility performance of microcrystalline cellulose type 101. In terms of powder flow properties, Avicel® and Alfacel® showed similar performance. However, the results revealed better powder flow employing microcrystalline cellulose type 102 for both excipients. Based on the results obtained, it can be concluded that the employment of innovative and generic excipients have both advantages and disadvantages. The observed differences however, tend to disappear as the excipients are diluted in a formulation, thereby equalizing their influence on product performance.A variedade de excipientes disponível no mercado requer adequada seleção desses no que se refere à sua funcionalidade, como no caso de celuloses microcristalinas (Avicel® 101 e 102 e Alfacel

  14. Lon protease affects the RdxA nitroreductase activity and metronidazole susceptibility in Helicobacter pylori.

    Science.gov (United States)

    Tu, I-Fan; Liao, Jiahn-Haur; Yang, Feng-Ling; Lin, Nien-Tsung; Chan, Hong-Lin; Wu, Shih-Hsiung

    2014-10-01

    The lon gene of Helicobacter pylori strains is constitutively expressed during growth. However, virtually nothing is understood concerning the role of Lon in H. pylori. This study examined the function and physiological role of Lon in H. pylori (HpLon) using a trapping approach to identify putative Lon binding partners in the bacterium. Protease-deficient Lon was expressed and served as the bait in trapping approach to capture the interacting partners in H. pylori. The antibiotic susceptibility of wild-type and lon derivative mutants was determined by the E test trips and the disc diffusion assay. The effect of HpLon on RdxA activity was detected the change in NADPH oxidation and metronidazole reduction by spectrophotometer. Lon in Helicobacter pylori (HpLon) interacting partners are mostly associated with metronidazole activation. lon mutant presents more susceptible to metronidazole than that of the wild type, and this phenotype is recovered by complementation of the wild-type Lon. We found that the ATPases associated with a variety of cellular activities (AAA(+) ) module of HpLon causes a decrease in both NADPH oxidase and Mtz reductase activity in RdxA, a major Mtz-activating enzyme in H. pylori. Metronidazole resistance of H. pylori causes the serious medical problem worldwide. In this study, HpLon is involved in metronidazole susceptibility among H. pylori strains. We provide the evidence that HpLon alters RdxA activity in vitro. The decrease in metronidazole activation caused by HpLon is possibly prior to accumulate mutation in rdxA gene before the metronidazole-resistant strains to be occurred. © 2014 John Wiley & Sons Ltd.

  15. The genetic diversity of metronidazole susceptibility in Trichomonas vaginalis clinical isolates in an Egyptian population.

    Science.gov (United States)

    Abdel-Magied, Aida A; El-Kholya, El-Said I; Abou El-Khair, Salwa M; Abdelmegeed, Eman S; Hamoudaa, Marwa M; Mohamed, Sara A; El-Tantawy, Nora Labeeb

    2017-11-01

    Trichomoniasis is the most common curable sexually transmitted disease worldwide. Resistance to metronidazole in treating trichomoniasis is a problematic health issue. We aimed to determine the minimum lethal concentration (MLC) of metronidazole for Trichomonas vaginalis isolates detected in Mansoura, Egypt and studied the genotypic profile of these isolates. Vaginal swab specimens were obtained from 320 symptomatic and 100 asymptomatic females, for whom clinical examination, vaginal discharge wet mount, Giemsa stain, and culture in modified Diamond's media were performed. Metronidazole susceptibility testing by an aerobic tube assay was performed. Both sensitive and resistant isolates were examined by PCR amplification followed by restriction fragment length polymorphism (RFLP). Trichomonas vaginalis was identified in 49/420 (11.7%) using either culture or PCR, while wet mount and Giemsa stain detected the parasite in 8.1 and 7.6% of participants, respectively. After 48 h incubation, most isolates were sensitive to metronidazole with a minimal lethal concentration (MLC) of 1 μg/ml. Mild resistance was observed in two isolates with MLCs of 64 μg\\ml and mild to moderate resistance was observed in an additional two isolates with MLCs of 128 μg/ml. The four isolates that demonstrated low to moderate metronidazole resistance displayed a unique genotype band pattern by RFLP compared to the other 45 samples that were metronidazole sensitive. Our results highlight the presence of in vitro metronidazole tolerance in a few T. vaginalis isolates in Mansoura, Egypt that may lead to the development of drug resistance as well as the possibility of an identifying RFLP pattern in the isolates.

  16. Detection of metronidazole in honey and metronidazole tablets using carbon dots-based sensor via the inner filter effect.

    Science.gov (United States)

    Zhao, Jianru; Pan, Xiaohua; Sun, Xiaobo; Pan, Wei; Yu, Guifeng; Wang, Jinping

    2018-06-01

    In this work, carbon dots (CDs) with a high quantum yield (22.3%) were easily prepared by hydrothermal pyrolysis of acid fuchsin 6B and hydrogen peroxide at 180°C for 10 h. The resultant CDs possess a narrow size distribution in the range of 2.6 to 3.2 nm and emit blue fluorescence. Interestingly, the absorption band of metronidazole (MTZ) centered at 318 nm can complementary overlap with the excitation band of the as-prepared CDs centered at 320 nm, resulting in an inner filter effect (IFE) in high efficiency. In fact, the fluorescence quenching of the CDs depends on the concentration of MTZ. Therefore, a simple method for the detection of MTZ can be established using the CDs-based sensor via the IFE. The linear range of the proposed method was 0-10 μg mL -1 with the limit of detection as low as 0.257 μg mL -1 . This CDs-based sensor had been applied for the detection of MTZ in honey and MTZ tablets with the recoveries in the range of 98.0% to 105.1% and 95.7% to 106.5%, respectively. Therefore, the as-prepared CDs have a potential to be developed as a MTZ sensor with high selectivity, sensitivity and accuracy. Copyright © 2018 John Wiley & Sons, Ltd.

  17. Antibiotic prophylaxis for hysterectomy, a prospective cohort study: cefuroxime, metronidazole, or both?

    Science.gov (United States)

    Brummer, T H I; Heikkinen, A-M; Jalkanen, J; Fraser, J; Mäkinen, J; Tomás, E; Seppälä, T; Sjöberg, J; Härkki, P

    2013-09-01

    To evaluate cefuroxime and metronidazole antibiotic prophylaxis. Observational nonrandomised 1-year prospective cohort study. Fifty-three hospitals in Finland. A total of 5279 women undergoing hysterectomy for benign indications, with cefuroxime given to 4301 and metronidazole given to 2855. Excluding other antibiotics, cefuroxime alone was given to 2019, metronidazole alone was given to 518, and they were administered in combination to 2252 women. Data on 1115 abdominal hysterectomies (AHs), 1541 laparoscopic hysterectomies (LHs), and 2133 vaginal hysterectomies (VHs) were analysed using logistic regression adjusted for confounding factors. Postoperative infections. Cefuroxime had a risk-reductive effect for total infections (adjusted odds ratio, OR, 0.29; 95% confidence interval, 95% CI, 0.22-0.39), but the independent effect of metronidazole and the interaction effect of cefuroxime and metronidazole were nonsignificant. In subgroup analyses of AHs, LHs, and VHs involving those receiving the two main antibiotics only, the effect of cefuroxime alone nonsignificantly differed from that of cefuroxime and metronidazole in combination for all types of infection. The absence of cefuroxime, assessed by comparing metronidazole alone with cefuroxime and metronidazole in combination, led to an increased risk for total infections in AHs (adjusted OR 3.63; 95% CI 1.99-6.65), in LHs (OR 3.53; 95% CI 1.74-7.18), and in VHs (OR 4.05; 95% CI 2.30-7.13), and also increased risks for febrile events in all categories (AHs, OR 2.86; 95% CI 1.09-7.46; LHs, OR 13.19; 95% CI 3.66-47.49; VHs, OR 12.74; 95% CI 3.01-53.95), wound infections in AHs (OR 6.88; 95% CI 1.09-7.49), and pelvic infections in VHs (OR 4.26; 95% CI 1.76-10.31). In this study, cefuroxime appeared to be effective in prophylaxis against infections. Metronidazole appeared to be ineffective, with no additional risk-reductive effect when combined with cefuroxime. © 2013 RCOG.

  18. [Intestinal disorder of anaerobic bacteria aggravates pulmonary immune pathological injury of mice infected with influenza virus].

    Science.gov (United States)

    Wu, Sha; Yan, Yuqi; Zhang, Mengyuan; Shi, Shanshan; Jiang, Zhenyou

    2016-04-01

    To investigate the relationship between the intestinal disorder of anaerobic bacteria and influenza virus infection, and the effect on pulmonary inflammatory cytokines in mice. Totally 36 mice were randomly divided into normal control group, virus-infected group and metronidazole treatment group (12 mice in each group). Mice in the metronidazole group were administrated orally with metronidazole sulfate for 8 days causing anaerobic bacteria flora imbalance; then all groups except the normal control group were treated transnasally with influenza virus (50 μL/d FM1) for 4 days to establish the influenza virus-infected models. Their mental state and lung index were observed, and the pathological morphological changes of lung tissues, caecum and intestinal mucosa were examined by HE staining. The levels of interleukin 4 (IL-4), interferon γ (IFN-γ), IL-10 and IL-17 in the lung homogenates were determined by ELISA. Compared with the virus control group, the metronidazole group showed obviously increased lung index and more serious pathological changes of the lung tissue and appendix inflammation performance. After infected by the FM1 influenza virus, IFN-γ and IL-17 of the metronidazole group decreased significantly and IL-4 and IL-10 levels were raised, but there was no statistically difference between the metronidazole and virus control groups. Intestinal anaerobic bacteria may inhibit the adaptive immune response in the lungs of mice infected with FM1 influenza virus through adjusting the lung inflammatory factors, affect the replication and clean-up time of the FM1 influenza virus, thus further aggravating pulmonary immune pathological injury caused by the influenza virus infection.

  19. Chlorinated metronidazole as a promising alternative for treating trichomoniasis.

    Science.gov (United States)

    Chacon, M O; Fonseca, T H S; Oliveira, S B V; Alacoque, M A; Franco, L L; Tagliati, C A; Cassali, G D; Campos-Mota, G P; Alves, R J; Capettini, L S A; Gomes, Maria Aparecida

    2018-05-01

    Trichomoniasis is the most common non-viral, sexually transmitted infection affecting humans worldwide. The main treatment for trichomoniasis is metronidazole (MTZ). However, adverse effects and reports of resistance have stimulated the development of therapeutic alternatives. The ease of manipulation of the side chains of MTZ coupled with its safety makes this molecule attractive for the development of new drugs. In this context, we evaluated the activity of the chlorinated MTZ derivative, MTZ-Cl, on sensitive and resistant strains of Trichomonas vaginalis. MTZ-Cl presented a remarkable activity against both sensitive and resistant strains. In vitro and in vivo toxicity assays indicated that the new molecule is safe for future clinical trials. Furthermore, we noticed different rates of free radical production between the sensitive and resistant strains. MTZ-Cl induced a higher release of nitric oxide (NO, ~ 9000 a.u.) by both sensitive and resistant strains. However, the sensitive strain produced a greater amount of H 2 O 2 (~ 1,800,000 a.u.) and superoxide radicals (~ 350,000 a.u.) in the presence of MTZ. In the resistant strain, production of these radicals was more prominent when MTZ-Cl was used. Collectively, these results suggest that NO is an important molecule in the trichomonacidal activity against resistant and sensitive strains, suggesting an alternative pathway for MTZ-Cl activation. We highlight the high trichomonacidal potential of MTZ-Cl, improving the effectiveness of treatment and reducing side effects. In addition, MTZ-Cl is derived from a well-established drug on the world market that presents low toxicity to human cells, suggesting its safety to proceed with future clinical trials.

  20. Experience of successful treatment of patients with metronidazole-resistant Trichomonas vaginalis with zinc sulfate: A case series

    Directory of Open Access Journals (Sweden)

    Jung Mi Byun

    2015-10-01

    Conclusion: Although the exact role of zinc sulfate in metronidazole-resistant trichomoniasis is not clear, our patients experienced a therapeutic effect with zinc sulfate douche treatment. We therefore recommend zinc sulfate douche as an option for the treatment of metronidazole-resistant vaginal trichomoniasis.

  1. Nizatidine and omeprazole enhance the effect of metronidazole on Helicobacter pylori in vitro

    DEFF Research Database (Denmark)

    Chen, Ming; Jensen, Bente; Zhai, Lin

    2002-01-01

    to reverse antibiotic resistance do not necessarily have an antibiotic or chemotherapeutic effect in the sense of growth inhibition. Therefore, it was decided to investigate the effect of nizatidine and omeprazole on the oxidative respiratory chain, as it is known that metronidazole is able to inhibit...... the activity of fumarate reductase of H. pylori. This enzyme is a key enzyme in the alternative respiratory chain under anaerobic conditions. Nizatidine was, in these preliminary experiments, found to inhibit fumarate reductase in a dose-dependent way, like metronidazole, whereas omeprazole had almost...... no effect on fumarate reductase. No other significant effects on the enzymes of the respiratory chain were found. The synergistic effect of nizatidine on metronidazole resistant H. pylori strains could be explained by the effect on fumarate reductase, whereas the effect of omeprazole is different and could...

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

    Science.gov (United States)

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

    2016-01-01

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

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

    Science.gov (United States)

    Dahlen, G; Preus, H R

    2017-02-01

    The objective of this study was to assess antibiotic susceptibility among predominant Gram-negative anaerobic bacteria isolated from periodontitis patients who 5 years prior had been subject to mechanical therapy with or without adjunctive metronidazole. One pooled sample was taken from the 5 deepest sites of each of 161 patients that completed the 5 year follow-up after therapy. The samples were analyzed by culture. A total number of 85 anaerobic strains were isolated from the predominant subgingival flora of 65/161 patient samples, identified, and tested for antibiotic susceptibility by MIC determination. E-tests against metronidazole, penicillin, amoxicillin, amoxicillin + clavulanic acid and clindamycin were employed. The 73/85 strains were Gram-negative rods (21 Porphyromonas spp., 22 Prevotella/Bacteroides spp., 23 Fusobacterium/Filifactor spp., 3 Campylobacter spp. and 4 Tannerella forsythia). These were all isolated from the treated patients irrespective of therapy procedures (+/-metronidazole) 5 years prior. Three strains (Bifidobacterium spp., Propionibacterium propionicum, Parvimonas micra) showed MIC values for metronidazole over the European Committee on Antimicrobial Susceptibility Testing break point of >4 μg/mL. All Porphyromonas and Tannerella strains were highly susceptible. Metronidazole resistant Gram-negative strains were not found, while a few showed resistance against beta-lactam antibiotics. In this population of 161 patients who had been subject to mechanical periodontal therapy with or without adjunct metronidazole 5 years prior, no cultivable antibiotic resistant anaerobes were found in the predominant subgingival microbiota. Copyright © 2016 Elsevier Ltd. All rights reserved.

  4. Metronidazole-containing gel for the treatment of periodontitis: an in vivo evaluation

    Directory of Open Access Journals (Sweden)

    Sandra Sato

    2008-06-01

    Full Text Available The aim of this investigation was to monitor metronidazole concentrations in the gingival crevicular fluid (GCF collected from periodontal pockets of dogs after treatment with an experimental 15% metronidazole gel. Five dogs had periodontitis induced by cotton ligatures placed subgingivally and maintained for a 30-day period. After the induction period, only pockets with 4 mm or deeper received the gel. Each pocket was filled up to the gingival margin by means of a syringe with a blunt-end needle. GCF was collected in paper strips and quantified in an electronic device before and after 15 minutes, 1 h, 6 h, 24 h and 48 h of gel administration. The GCF samples were assayed for metronidazole content by means of a high performance liquid chromatography method. Concentrations of metronidazole in the GCF of the 5 dogs (mean ± SD, in µg/mL were 0 ± 0 before gel application and 47,185.75 ± 24,874.35 after 15 minutes, 26,457.34 ± 25,516.91 after 1 h, 24.18 ± 23.11 after 6 h, 3.78 ± 3.45 after 24 h and 3.34 ± 5.54 after 48 h. A single administration of the 15% metronidazole gel released the drug in the GCF of dogs in levels several-fold higher than the minimum inhibitory concentration for some periodontopathogens grown in subgingival biofilms for up to one hour, but metronidazole could be detected in the GCF at least 48 hours after the gel application.

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

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    Mohammad MATINI

    2016-03-01

    Full Text Available 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.

  6. Effect of antimicrobial therapy on bowel flora and bacterial infection in irradiated mice

    Energy Technology Data Exchange (ETDEWEB)

    Brook, Itzhak; Walker, R.I.; MacVittie, T.J.

    1988-05-01

    Mice exposed to 10 Gy cobalt-60 radiation were given intramuscular antimicrobial therapy of gentamicin, metronidazole, or a combination. Mortality in mice treated with metronidazole alone or in combination with gentamicin occurred earlier than in controls (P < 0.001). Microorganisms were recovered from blood, spleen, and liver of the metronidazole-treated mice earlier than from other groups. Predominant organisms recovered from these animals were Enterobacteriaceae. Quantitative cultures of ileal flora showed decrease in aerobic, facultative anaerobic and strict anaerobic bacteria after irradiation, and a subsequent increase only in the number of strict aerobic bacteria. Compared to untreated mice, a rapid decrease (by 8.8 logs) in anaerobic flora occurred in mice treated with metronidazole 5 days after irradiation, followed by a rapid increase in the number of aerobic organisms which coincided with the earlier mortality in this group. Data suggest that antimicrobial agents decreasing the number of the strict anaerobic component of the gut flora enhance systemic infection by aerobic or facultative anaerobic bacteria, facilitating post-irradiation mortality.

  7. Effect of antimicrobial therapy on bowel flora and bacterial infection in irradiated mice

    International Nuclear Information System (INIS)

    Brook, Itzhak; Walker, R.I.; MacVittie, T.J.

    1988-01-01

    Mice exposed to 10 Gy cobalt-60 radiation were given intramuscular antimicrobial therapy of gentamicin, metronidazole, or a combination. Mortality in mice treated with metronidazole alone or in combination with gentamicin occurred earlier than in controls (P < 0.001). Microorganisms were recovered from blood, spleen, and liver of the metronidazole-treated mice earlier than from other groups. Predominant organisms recovered from these animals were Enterobacteriaceae. Quantitative cultures of ileal flora showed decrease in aerobic, facultative anaerobic and strict anaerobic bacteria after irradiation, and a subsequent increase only in the number of strict aerobic bacteria. Compared to untreated mice, a rapid decrease (by 8.8 logs) in anaerobic flora occurred in mice treated with metronidazole 5 days after irradiation, followed by a rapid increase in the number of aerobic organisms which coincided with the earlier mortality in this group. Data suggest that antimicrobial agents decreasing the number of the strict anaerobic component of the gut flora enhance systemic infection by aerobic or facultative anaerobic bacteria, facilitating post-irradiation mortality. (author)

  8. The use of immobilized form of benzalkonium chloride and metronidazole in the treatment of purulent wounds

    OpenAIRE

    Anastasia S. Gorohova; Arsen Yu. Grigoryan; Alexander I. Bezhin; Tatyana A. Pankrusheva; Boris S. Sukovatykh; Ludmila V. Zhilyaeva; Ekaterina S. Mishina; Elena V. Kobzareva

    2017-01-01

    The purpose of the study is to investigate the wound-healing effect of the immobilized form of benzalkonium chloride and metronidazole based on the sodium salt of carboxymethylcellulose (Na-CMC) or polyethylene oxide (PEO) in the treatment of an experimental purulent wound.Materials and methods. The following compositions were studied, %. Combination 1: benzalkonium chloride – 0.02; Metronidazole – 1,0; Sodium carboxymethylcellulose (NaCMC) – 4,0; Purified water – up to 100,0. Combination 2: ...

  9. Bismuth, lansoprazole, amoxicillin and metronidazole or clarithromycin as first-line Helicobacter pylori therapy.

    Science.gov (United States)

    Zhang, Wei; Chen, Qi; Liang, Xiao; Liu, Wenzhong; Xiao, Shudong; Graham, David Y; Lu, Hong

    2015-11-01

    To evaluate the efficacy and tolerability of replacing tetracycline with amoxicillin in bismuth quadruple therapy. Subjects who were infected with Helicobacter pylori and naïve to treatment were randomly (1:1) assigned to receive a 14-day modified bismuth quadruple therapy: lansoprazole 30 mg, amoxicillin 1 g, bismuth potassium citrate 220 mg (elemental bismuth), twice a day with metronidazole 400 mg four times a day (metronidazole group) or clarithromycin 500 mg twice a day (clarithromycin group). Six weeks after treatment, H. pylori eradication was assessed by 13C-urea breath test. Antimicrobial susceptibility was assessed by the twofold agar dilution method. This was a non-inferiority trial. Two hundred and fifteen subjects were randomised. Metronidazole and clarithromycin containing regimens achieved high cure rates: 94 of 97 (96.9%, 95% CI 93.5% to 100%) and 93 of 98 (94.9%, 95% CI 90.5% to 99.3%) by per-protocol and 88.9% (95% CI 83.0% to 94.8%) and 88.8% (95% CI 82.8% to 94.8%) by intention-to-treat, respectively. Amoxicillin, metronidazole and clarithromycin resistance rates were 1.5%, 45.5% and 26.5%, respectively. Only clarithromycin resistance reduced treatment success (e.g., susceptible 98.6%, resistant 76.9%, p=0.001). Adverse events were more common in the metronidazole group. These results suggest that amoxicillin can substitute for tetracycline in modified 14 day bismuth quadruple therapy as first-line treatment and still overcome metronidazole resistance in areas with high prevalence of metronidazole and clarithromycin resistance. Using clarithromycin instead of metronidazole was only effective in the presence of susceptible strains. NCT02175901. Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://group.bmj.com/group/rights-licensing/permissions.

  10. Flow injection determination of metronidazole through spectrophotometric measurement of the nitrite ion produced upon alkaline hydrolysis

    Directory of Open Access Journals (Sweden)

    Simões Simone S.

    2006-01-01

    Full Text Available A new method for metronidazole determination, based on spectrometric monitoring of a diazonium salt produced in-line by alkaline hydrolysis released nitrite ions, was developed and successfully applied to pharmaceutical tablets (r = 0.9993, 2.0-20.0 mg L-1, DL = 0.7 mg L-1 with no interference from common ingredients accompanying the drug.

  11. Resistance pattern of Helicobacter pylori strains to clarithromycin, metronidazole, and amoxicillin in Isfahan, Iran

    Directory of Open Access Journals (Sweden)

    Farzad Khademi

    2013-01-01

    Full Text Available Background: Helicobacter pylori (H. pylori resistance to antibiotics has become a global problem and is an important factor in determining the outcome of treatment of infected patients. The purpose of this study was to determine the H. pylori resistance to clarithromycin, metronidazole, and amoxicillin in gastrointestinal disorders patients. Materials and Methods: In this study, a total of 260 gastric antrum biopsy specimens were collected from patients with gastrointestinal disorders who referred to Endoscopy Section of the Isfahan Hospitals. The E-test and Modified Disk Diffusion Method (MDDM were used to verify the prevalence of antibiotic resistance in 78 H. pylori isolates to the clarithromycin, metronidazole, and amoxicillin. Results: H. pylori resistance to clarithromycin, metronidazole, and amoxicillin were 15.3, 55.1, and 6.4%, respectively. In this studyΈ we had one multidrug resistance (MDR isolates from patient with gastritis and peptic ulcer disease. Conclusion: Information on antibiotic susceptibility profile plays an important role in empiric antibiotic treatment and management of refractive cases. According to the results obtained in this study, H. pylori resistance to clarithromycin and metronidazole was relatively high. MDR strains are emerging and will have an effect on the combination therapy.

  12. Synergic activity, for anaerobes, of trovafloxacin with clindamycin or metronidazole: chequerboard and time-kill methods.

    Science.gov (United States)

    Ednie, L M; Credito, K L; Khantipong, M; Jacobs, M R; Appelbaum, P C

    2000-05-01

    Chequerboard titrations were used to test the activity of trovafloxacin, alone and in combination with clindamycin or metronidazole, against 156 Gram-positive or Gram-negative anaerobes, including 47 Bacteroides fragilis group, 36 Prevotella spp., 26 fusobacteria, 21 peptostreptococci and 26 clostridia. MIC50/MIC90 values (mg/L) of each drug alone against all 156 strains were: trovafloxacin, 0.5/1; clindamycin, 0.25/2; metronidazole, 1/2. Synergy (FIC indices 0. 5-2.0); no antagonism (FIC indices >4.0) was seen. In addition, synergy was tested by time-kill methodology for each of the above combinations against 12 Gram-positive or Gram-negative strains. Results indicated that synergy (defined as a >/= 2 log(10) decrease in cfu/mL at 48 h compared with the more active drug alone) was found between trovafloxacin at or below the MIC and both clindamycin and metronidazole at or below the MIC in one strain each of Bacteroides fragilis, Bacteroides thetaiotaomicron, Prevotella intermedia, Fusobacterium varium, Peptostreptococcus asaccharolyticus and Clostridium bifermentans. Synergy between trovafloxacin (metronidazole alone was seen in one strain each of Bacteroides distasonis, Prevotella bivia, Fusobacterium mortiferum, P. asaccharolyticus and C. bifermentans. In many cases of synergy, including those at the trovafloxacin MIC, regrowth after 48 h, which was commonly seen with trovafloxacin alone, was inhibited, and 99.9% killing was observed with the combination after 48 h, but not with trovafloxacin alone.

  13. Comparison of local metronidazole and a local antiseptic in the treatment of bacterial vaginosis.

    Science.gov (United States)

    Novakov Mikic, Aleksandra; Budakov, Dragan

    2010-07-01

    Bacterial vaginosis (BV) is characterized by a mixed flora of pathogenic anaerobic bacteria and associated with risks of pathologic conditions. In the present study, therapy with a local antiseptic spray (octenidine hydrochloride/phenoxyethanol, OHP) for 7 or 14 days is compared against the standard local therapy of BV (metronidazole) in a Serbian patient population. As much as 450 women were treated in groups with either 7 days metronidazole vaginal tablets, 7 days OHP, or 14 days OHP. Control smears were taken after each treatment period. In total, 63.2% of the women were without indications of BV after therapy (metronidazole: 61.0%, OHP 7 days: 57.6%, and OHP 14 days: 71.0%). Significantly fewer women were affected from infections after treatment with 14 days OHP compared to OHP for 7 days. Octenidine hydrochloride/phenoxyethanol spray was as effective as the standard therapy with metronidazole. Patients stated that OHP was more comfortable, easier to apply, and side effects were lesser.

  14. Granulomatous cheilitis: sustained response to combination of intralesional steroids, metronidazole and minocycline

    International Nuclear Information System (INIS)

    Dar, N.R.; Raza, N.; Nadeem, A.; Manzoor, A.

    2007-01-01

    Various conservative methods for treatment of labial swelling in patients with granulomatous cheilitis have been attempted, often with only moderate success. We report a case of granulomatous cheilitis who showed excellent sustained response to combination of intralesional steroids, metronidazole and minocycline for initial one month followed by prolonged maintenance treatment with minocycline alone. (author)

  15. Separation of metronidazole, its major metabolites and their conjugates using dynamically modified silica

    DEFF Research Database (Denmark)

    Thomsen, U. G.; Cornett, Claus; Tjornelund, J.

    1995-01-01

    -performance liquid chromatographic (HPLC) system for the simultaneous determination of metronidazole, its major metabolites and their glucuronic acid conjugates in biological fluids. The separation is performed using bare silica dynamically modified with N-cetyl-N,N,N-trimethylammonium bromide contained...

  16. Radiosynthesis and Biodistribution of 99mTc-Metronidazole as an Escherichia coli Infection Imaging Radiopharmaceutical.

    Science.gov (United States)

    Iqbal, Anam; Naqvi, Syed Ali Raza; Rasheed, Rashid; Mansha, Asim; Ahmad, Matloob; Zahoor, Ameer Fawad

    2018-05-01

    Bacterial infection poses life-threatening challenge to humanity and stimulates to the researchers for developing better diagnostic and therapeutic agents complying with existing theranostic techniques. Nuclear medicine technique helps to visualize hard-to-diagnose deep-seated bacterial infections using radionuclide-labeled tracer agents. Metronidazole is an antiprotozoal antibiotic that serves as a preeminent anaerobic chemotherapeutic agent. The aim of this study was to develop technetium-99m-labeled metronidazole radiotracer for the detection of deep-seated bacterial infections. Radiosynthesis of 99m Tc-metronidazole was carried by reacting reduced technetium-99m and metronidazole at neutral pH for 30 min. The stannous chloride dihydrate was used as the reducing agent. At optimum radiolabeling conditions, ~ 94% radiochemical was obtained. Quality control analysis was carried out with a chromatographic paper and instant thin-layer chromatographic analysis. The biodistribution study of radiochemical was performed using Escherichia coli bacterial infection-induced rat model. The scintigraphic study was performed using E. coli bacterial infection-induced rabbit model. The results showed promising accumulation at the site of infection and its rapid clearance from the body. The tracer showed target-to-non-target ratio 5.57 ± 0.04 at 1 h post-injection. The results showed that 99m Tc-MNZ has promising potential to accumulate at E. coli bacterial infection that can be used for E. coli infection imaging.

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

    Science.gov (United States)

    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.

  18. Evaluation of HP0605 and HP0971 genes of efflux pumps in Helicobacter pylori resistance to Metronidazole

    Directory of Open Access Journals (Sweden)

    Mohammad hasan Shirazi

    2009-12-01

    Full Text Available Background: The presence of antibiotic resistance has been reported in H.pylori and it is a major cause of treatment failure. Five families of multidrug efflux pumps are defined in bacteria and resistance-nodulation-division (RND pumps are found mainly in gram negative bacteria. TolC is one of RND pump components and play a critical role in drug resistance. It hasn’t been established that RND family has a role in drug resistance in H.pylori. In this study, we assessed the role of two efflux genes in resistant to metronidazole in H.pylori by evaluation of overexpression TolC genes by RT-PCR method. Methods: In five metronidazole resistant strains of H.pylori, total RNA was extracted. RNA treated with DNase and RNA reverse transcribed to cDNA. Aliquots of the cDNA solution were assayed by RT- PCR for HP0605 and HP0971 genes. The levels of mRNA expression were evaluated by densitometry analysis. Results: All five strains displayed overexpression for HP0605 basis of increased concentration of metronidazole. Three strains showed transcripts for HP0971. One of these had transcripts for HP0971 only in Metronidazole concentration equaled to 16 µg/ml but two strains overexpressed adapt to increase concentration of metronidazole. Conclusion: According to current study, HP0605 and HP0971 genes overexpressed due to increase metronidazole. So, increasing of Metronidazole affects in H.pylori΄s efflux system in transcription level.

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

    Science.gov (United States)

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

    2016-01-01

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

  20. Reducing surgical site infections after hysterectomy: metronidazole plus cefazolin compared with cephalosporin alone.

    Science.gov (United States)

    Till, Sara R; Morgan, Daniel M; Bazzi, Ali A; Pearlman, Mark D; Abdelsattar, Zaid; Campbell, Darrell A; Uppal, Shitanshu

    2017-08-01

    Organisms that are isolated from vaginal cuff infections and pelvic abscesses after hysterectomy frequently include anaerobic vaginal flora. Metronidazole has outstanding coverage against nearly all anaerobic species, which is superior to both cefazolin and second-generation cephalosporins. Cefazolin plus metronidazole has been demonstrated to reduce infectious morbidity compared with either cefazolin or second-generation cephalosporins in other clean-contaminated procedures, which include both as colorectal surgery and cesarean delivery. The purpose of this study was to evaluate whether the combination of cefazolin plus metronidazole before hysterectomy was more effective in the prevention of surgical site infection than existing recommendations of cefazolin or second-generation cephalosporin. This was a retrospective cohort study of patients in the Michigan Surgical Quality Collaborative from July 2012 through February 2015. The primary outcome was surgical site infection. Patients who were >18 years old and who underwent abdominal, vaginal, laparoscopic, or robotic hysterectomy for benign or malignant indications were included if they received 1 of the following prophylactic antibiotic regimens: cefazolin, second-generation cephalosporin, or cefazolin plus metronidazole. Multivariate logistic regression modeling was performed to evaluate the independent effect of an antibiotic regimen, and propensity score matching was used to validate the findings. The study included 18,255 hysterectomies. The overall rate of surgical site infection was 1.8% (n=329). The unadjusted rate of surgical site infection was 1.8% (n=267) for cefazolin, 2.1% (n=49) for second-generation cephalosporin, and 1.4% (n=13) for cefazolin plus metronidazole. After adjustment for differences in patient and operative factors among the antibiotic cohorts, compared with cefazolin plus metronidazole, we found the risk of surgical site infection was significantly higher for patients who received

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

    Energy Technology Data Exchange (ETDEWEB)

    Prabhakaran, Molamma P., E-mail: nnimpp@nus.edu.sg [Center for Nanofibers and Nanotechnology, Department of Mechanical Engineering, Faculty of Engineering, National University of Singapore, 2 Engineering Drive 3, Singapore 117576 (Singapore); Zamani, Maedeh [Center for Nanofibers and Nanotechnology, Department of Mechanical Engineering, Faculty of Engineering, National University of Singapore, 2 Engineering Drive 3, Singapore 117576 (Singapore); Felice, Betiana [Center for Nanofibers and Nanotechnology, Department of Mechanical Engineering, Faculty of Engineering, National University of Singapore, 2 Engineering Drive 3, Singapore 117576 (Singapore); Laboratorio de Medios e Interfases, Departamento de Bioingeniería, Universidad Nacional de Tucumán, Av. Independencia 1800, Tucumán (Argentina); Ramakrishna, Seeram [Center for Nanofibers and Nanotechnology, Department of Mechanical Engineering, Faculty of Engineering, National University of Singapore, 2 Engineering Drive 3, Singapore 117576 (Singapore)

    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 ± 407 nm and 1774 ± 167 nm, 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 41 days. 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. - Highlights: • Electrospraying as a novel method for the fabrication of drug delivery device • Metronidazole encapsulated PLGA particles were fabricated by electrospraying. • Solvent DCM produced particles of double the size than using TFE. • Sustained release of metronidazole studied for a period of 41 days • Drug release pattern from particles followed Fickian diffusion. • PLGA-metronidazole particles can function as a substrate for periodontal regeneration.

  2. Misonidazole cytotoxicity in vivo: a comparison of large single doses with smaller doses and extended contact of the drug with tumor cells

    International Nuclear Information System (INIS)

    Conroy, P.J.; Sutherland, R.M.; Passalacqua, W.

    1980-01-01

    Experiments were performed to determine the kinetics and magnitude of misonidazole cytotoxicity in EMT6/Ro tumors using an in vivo-in vitro clonogenicity assay. A comparison was made between the cytotoxic effects of large single doses with smaller doses of misonidazole administered ip and those produced on extended contact of the drug with tumor cells using a continuous iv drug infusion system. After a single ip dose of 1 mg/g, cytotoxicity was maximum at 18 to 24 h; by 72 h the clonogenic cells per tumor had returned to control levels. The maximum cytotoxicity was greater (a decrease of 10 times) if the animals were kept at 37 0 C compared with ambient conditions (a decrease of 4.5 times) where the body temperature would decrease due to the drug. A dose-response curve performed with the animals at 37 0 C showed no significant cytotoxicity at 18 h after single ip doses of 0.5 mg/g or less. Other experiments were carried out at 37 0 C using a drug continuous infusion system. Two profiles were studied: (a) continuous constant rate infusion over 3 days of constant serum and tumor levels of both 100 and 200 μg/ml and (b) continuous variable rate infusion where the maximum serum levels reached 80 or 200 μg/ml after 2 to 4 h and decayed with a half-life of 12 h as in humans. Significant cytotoxicity was obtained under both of these conditions. Maximum cytotoxicity occurred at about 24 h in both types of experiments and amounted to decreases of clonogenic tumor cells of 4.5 and 7 times for 100 and 200 μg/ml, respectively, after constant rate infusion and 2 to 4 times for 80 and 200 μg/ml, respectively, after variable rate infusion. Because of the relatively rapid recovery in the number of clonogenic tumor cells by 72 h, the cytotoxic effects were not reflected as changes in tumor size even when the animals were maintained at 37 0 C

  3. Study of the removal of metronidazole from aqueous solutions using Electro/ Fenton process and graphite and iron electrodes

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    Bahram Kamarehie

    2018-04-01

    Conclusion: The Electro-Fenton process can effectively remove metronidazole from aquatic solutions in environmentally convenient conditions. This process can be used as an efficient method for removing other persistent pollutants from the environment.

  4. Effect of lactic acid suppositories compared with oral metronidazole and placebo in bacterial vaginosis: a randomised clinical trial.

    Science.gov (United States)

    Boeke, A J; Dekker, J H; van Eijk, J T; Kostense, P J; Bezemer, P D

    1993-01-01

    OBJECTIVE--To compare the effect of lactic acid locally, metronidazole orally and placebo in women with bacterial vaginosis. DESIGN--Randomised clinical trial. SETTING--30 general practices in the Netherlands. PATIENTS--125 women consulting the general practitioner for symptomatic bacterial vaginosis. MAIN OUTCOME MEASURES--Duration of subjective symptoms, recurrence of symptoms, clinically diagnosed cure, adverse events. RESULTS--Survival analysis showed a significantly faster disappearance of symptoms in the metronidazole category compared with both lactic acid and placebo (p = 0.0005 metronidazole v placebo, p = 0.0002 metronidazole v lactic acid p = 0.6521 lactic acid v placebo [The stratified Mantel Cox test]). The median duration until absence of symptoms was 21 days for metronidazole and 80 days for placebo. Disappearance of symptoms did not occur in 50% of the lactic acid group in 90 days. Recurrence rates of symptoms were similar over the treatment categories (p = 0.13 metronidazole v placebo and p = 0.12 lactic acid v placebo). After 2 weeks cure rates (cure defined as less than three of four clinical criteria present) were 83%, 49% and 47% for metronidazole, lactic acid and placebo category respectively. At that time cure rates (cure defined as none of three clinical criteria present) were 10%, 0% and 3%. After four weeks and three months these figures were: 55%, 20%, 20% and 64%, 28%, 28%. No differences in adverse events were found between the three interventions. CONCLUSIONS--Lactic acid suppositories are ineffective, metronidazole capsules are effective on signs and symptoms in bacterial vaginosis. A considerable proportion of the patients recover without active medication. PMID:8244360

  5. A meta-analysis of the effectiveness of albendazole compared with metronidazole as treatments for infections with Giardia duodenalis.

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    Shahram Solaymani-Mohammadi

    2010-05-01

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

  6. Efficacy of drugs against Giardia muris in mice Mus musculus naturally infected/
    Eficácia de drogas contra Giardia muris em camundongos Mus musculus naturalmente infectados

    OpenAIRE

    Silvia Gonzalez Monteiro; Régis Adriel Zanette; Camila Belmonte Oliveira; Marcos Kipper da Silva; Aleksandro Schafer da Silva

    2008-01-01

    This study aimed to evaluate the efficacy of metronidazole, fenbendazole and secnidazole against Giardia muris in mice naturally infected. Forty mice of the species Mus musculus were divided in four groups of ten each, being group A non treated, the control group and groups B, C and D treated with 4mg/ml of metronidazole, fenbendazole and secnidazole, respectively. Two feces collection, on day 0 and on day 10 after treatment, were done in order to evaluate the efficacy of the drugs. Samples w...

  7. Efficacy and safety of oral tinidazole and metronidazole in treatment of bacterial vaginosis: a randomized control trial

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    Zahra Abbaspoor

    2014-05-01

    Full Text Available Aims: Oral metronidazole 500 mg twice a day for one week is currently the treatment of choice for bacterial vaginosis (BV. Complete treatment by this regimen takes time and occurs less often. This drug has significant side effects too. Using a drug in the shortest treatment course may increases the success of treatment. To evaluate the effectiveness and safety of oral tinidazole compare to metronidazole in treatment of BV.Methods: In this randomized, controlled, double-blind, comparative, clinical trial, 110 non-pregnant women aged between 15-45 years with confirmed diagnosis of BV by Amsels criteria were randomly assigned to receive either 2 g tinidazole tablet once daily for 2 days (n=55 or 500 mg metronidazole table twice daily for 7 days (n=55.The cure and recurrence rate were evaluated in both groups after 2 and 4 weeks follow up visits. For statistical analysis t-test,   test, fisher's exact test and Mann-Whitney test were used.Results: The results showed that cure rate after 2 weeks in tinidazole tablet group was 84.6٪ and in metronidazole group was 85.4٪ (p=0.9, and after 4 weeks recurrence rate in tinidazole and metronidazole groups was 6.9٪and 12.1٪respectively (P=0.3.Conclusions: Tinidazole table 2 g once daily for 2 days is as effective as metronidazole tablet 500 mg twice a day for 7 days in treatment of BV.

  8. Effects of binding metronidazole to a copper-acetate compound on radiosensitizer properties

    International Nuclear Information System (INIS)

    Negron, Ana C. Valderrama; Silva, Denise de Oliveira; Cruz, Aurea S.

    2009-01-01

    Copper compounds exhibit interesting biological properties. Nitroimidazoles show radiosensitizer properties for radiotherapy tumor treatment. In the present work, the effect of binding metronidazole (1-(2-hydroxyethyl)-2-methyl-5-nitroimidazole = MTZ) to copper-acetate on the radiosensitizer properties has been investigated. A compound of copper-acetate-MTZ was prepared and characterized. The experiments were carried out by gamma-irradiation of Hep2 (human larynx cancer) cells under hypoxic conditions. The radiation doses for 50% cell survival in the presence of radiosensitizer were about 8.2 Gy for CuAcMTZ or free MTZ. The effect of binding metronidazole to copper acetate on radiosensitizer properties is mainly related to the radiosensitizer process which involves two events for CuAcMTZ in contrast to one event observed for the MTZ free drug. (author)

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

    International Nuclear Information System (INIS)

    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

  10. Hypoxia-imaging with 18F-Misonidazole and PET: Changes of kinetics during radiotherapy of head-and-neck cancer

    International Nuclear Information System (INIS)

    Eschmann, Susanne Martina; Paulsen, Frank; Bedeshem, Claudia; Machulla, Hans-Juergen; Hehr, Thomas; Bamberg, Michael; Bares, Roland

    2007-01-01

    Background and purpose: PET with 18 F-Misonidazole (FMISO-PET) is a non-invasive method for measuring tumor hypoxia. We analysed changes of FMISO-uptake during radiotherapy and their impact on patient outcome. Materials and methods: Fourteen patients with HNC underwent repeated FMISO-PET prior to radiotherapy and after 30 Gy. Dynamic and static PET-scans (2 + 4 h p.i.) were acquired. FMISO-uptake was quantified by calculating standard uptake values (SUV) and tumor-muscle-ratios (TMR). Kinetic curve types representing tissue hypoxia were defined. Change of curve type was correlated with patient outcome. Results: The mean SUV 4 h p.i. and the TMR decreased significantly during radiotherapy. SUV decreased clearly in 12/14 patients, and increased in 2 patients. TMR decreased in 11 patients, and increased in 3 patients. Prior to radiotherapy, three different shapes of kinetic curve types indicative for the degree of hypoxia could be defined in 12/14 patients: (1) accumulation type (severe hypoxia (n = 8)) (2) intermediate type (intermediate degree of hypoxia (n = 3)), and (3) wash-out type (low degree of hypoxia (n = 1)). Curve type changed towards a lower degree of hypoxia at 30 Gy in all but 3 patients. In three patients curve type remained unchanged. Conclusions: The changes in tumor FMISO-uptake during radiotherapy indicate radio-induced reoxygenation

  11. Inhibition of X-ray-induced potentially lethal damage (PLD) repair in aerobic plateau-phase Chinese hamster cells by misonidazole

    International Nuclear Information System (INIS)

    Brown, D.M.

    1984-01-01

    The effect of the 2-nitroimidazole radiosensitizer misonidazole (MISO) and the hydrophilic analog SR-2508 on the repair of X-ray-induced potentially lethal damage (PLD) was studied in plateau-phase Chinese Hamster ovary (HA-1) cells. It was found that although MISO does not radiosensitize aerobic cells, it inhibits the repair of PLD. However, under hypoxic conditions, MISO has no effect on PLD repair. The major portion of the inhibition of PLD repair in aerobic cells requires the presence of MISO only during irradiation; little or no additional inhibition occurs when MISO is present during the postirradiation repair period. Also, treatment of aerobic cells with 5 mM MISO for either 5 or 30 min prior to irradiation is equally inhibitory. This suggests that the presence of MISO in some way modifies the initial lesion under aerobic conditions since it does not increase cell killing as determined by immediate plating but inhibits subsequent repair. The inhibition is concentration dependent; 0.5 mM MISO inhibits PLD repair by one-half while 5-10 mM totally inhibits the repair measured 6 hr postirradiation. This phenomenon suggests that radiosensitization of tissue in vivo by MISO and other 2-nitroimidazoles may not be unequivocal proof of the presence of hypoxic cells

  12. Effect of hyperthermia and misonidazole on the radiosensitivity of a transplant murine tumor: influence of factors modifying the fraction of hypoxic cells

    International Nuclear Information System (INIS)

    Wondergem, J.; Haveman, J.; van der Schueren, E.; van den Hoeven, H.; Breur, K.

    1982-01-01

    Hypoxia has been demonstrated to play an important role in the effect of hyperthermia on tumors. The influence of different factors modifying the oxygenation status of a transplantable murine mammary adenocarcinoma has been studied. The effect of hyperthermia alone on the tumor is not significantly influenced by the change in oxygenation status during the growth of the tumor. Also, the large increase of the acutely hypoxic cell fraction, as a result of anesthesia, does not change the effect of hyperthermia alone. In the combined irradiation-heat treatment there is a clear influence of the chronically hypoxic cell fraction on the response to hyperthermia: an increase in tumor size, resulting in a larger hypoxic cell fraction, leads to an increase in thermal enhancement ratio. However, the increased acutely hypoxic cell fraction, resulting from anesthesia, did not lead to an increase in thermal enhancement ratio; in fact the enhancement ratio apparently decreased. In spite of the fact that hyperthermia was applied immediately after irradiation no potentiation of radiation effects was found. The thermal enhancement of the radiation response was never larger than the enhancement as a result of misonidazole

  13. Combined radiation-protective and radiation-sensitizing agents. III. Radiosensitization by misonidazole as a function of concentrations of endogenous glutathione or exogenous thiols

    International Nuclear Information System (INIS)

    Koch, C.J.; Stobbe, C.C.; Baer, K.A.

    1986-01-01

    Radiosensitization of V79 Chinese hamster fibroblasts by 0.5 mM misonidazole is a smooth function of endogenous glutathione (GSH) levels as modulated upwards by pre-incubation in medium containing cysteamine, or downwards by pre-incubation in medium containing buthionine sulfoximine. The enhancement ratio (radiation sensitivity in nitrogen/radiation sensitivity in nitrogen +/- sensitizer or thiol) varies from 1.3 at 12 mM to 2.25 at less than 0.1 mM endogenous GSH. The enhanced radiosensitivity of thiol-depleted hypoxic cells is reversed when exogenous thiols are added, and for equivalent ER, the exogenous thiol concentrations are much lower than the endogenous GSH concentrations. Measurement of intracellular drug concentrations amplified rather than diminished the above discrepancy, since intracellular concentrations of cysteamine were lower and glutathione much lower than the extracellular concentrations. Three possible explanations are addressed: an external membrane component of damage is involved, long-range protection to DNA target radicals is possible from outside the cell (e.g., donation of electrons), and (c) endogenous glutathione is not in a free or exchangeable state (e.g., bound)

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

    Science.gov (United States)

    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.

  15. Histological investigation of a 10% metronidazole and 2% lidocaine dressing on wound healing in rats.

    Science.gov (United States)

    Rodrigues, T S; Poi, W R; Panzarini, S R; Bezerra, C S; Silva, J L

    2006-01-01

    Alveolitis is considered a disturbance of the alveolar healing process that is characterized by blood clot disintegration, alveolar wall infection and extreme pain. Several substances have been investigated to improve healing and guarantee postoperative comfort to patients. The aim of this study was to evaluate, microscopically, in rats, the healing process in non-infected tooth sockets, after application of a 10% metronidazole and 2% lidocaine dressing, using lanolin as vehicle and mint as flavoring. Forty-five rats (Rattus norvegicus albinus, Wistar) had their right incisor extracted and were randomly assigned to 3 groups (n=15): Group I (control): the sockets were filled with blood clot; Group II: application of adrenaline solution at 1:1 000 with an absorbent paper point during 1 min plus filling of the socket with a 10% metronidazole and 2% lidocaine dressing, with lanolin as vehicle, and mint as flavoring; Group III: filling of the socket with the 10% metronidazole and 2% lidocaine dressing, with lanolin as vehicle and mint as flavoring. After 6, 15 and 28 days postoperatively, 5 animals per group were euthanized with an injectable anesthetic overdose. Histological and statistical analyses were performed. The results showed that the 10% metronidazole and 2% lidocaine dressing with lanolin as vehicle and mint as flavoring yielded similar response as that of the normal repair group and may be used to prevent the onset of alveolitis in those cases in which any predisposing factor is present. The use of this dressing has shown a good postoperative patient's comfort and does not cause a significant delay in the alveolar healing process.

  16. Role of NADPH-insensitive nitroreductase gene to metronidazole resistance of Helicobacter pylori strains

    Directory of Open Access Journals (Sweden)

    M Kargar

    2010-06-01

    Full Text Available Background and the purpose of the study: Current anti-H. pylori therapies are based on the use of two antibiotics with a proton pump inhibitor and/or a bismuth component. Metronidazole is a key component of such combination therapies in Iran. The aim of this study was to determine the role of rdxA gene in resistant strains of H. pylori isolated from Shahrekord Hajar hospital to metronidazole. Methods: This study was a cross-sectional method, which was carried out on 263 patients who referred to endoscopy department of Hajar hospital, in 2007. Biopsy samples were cultured on selective Brucella agar containing 10% blood and incubated under microerophilic condition at 370C for 3 - 7 days. Suspected colonies were tested by Gram staining, urease, oxidase and catalase activities. Organisms were confirmed to be H. pylori on the basis of the presence of ureC(glmM gene by PCR .Specific primers were used for detection of rdxA gene mutation . Results: Eighty and four strains of H. pylori determined by PCR method. Of the isolated strains, 49 (58.33% were resistant, 7 (8.33% were semi-sensitive to metronidazole and 200bp deletion in rdxA gene was observed in 2 strains. Conclusion: Because of the high metronidazole resistance in patients under study it was necessary to replace it by other antibiotics in therapeutic regimens. On the basis of low frequency of resistance mutation in rdxA gene, sequence analysis for identification of other mechanisms is suggested.

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

    International Nuclear Information System (INIS)

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

    1980-01-01

    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

  18. Comparison of Resistant and Susceptible Strains of Trichomons vaginalis to Metronidazole Using PCR Method

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    M Fallah

    2012-09-01

    Full Text Available Background: Metronidazole is drug of choice recommended by WHO for treatment of trichomoniasis, however, some reports claims drug resistance in Trichomonas vaginalis isolates recently. The objective of this study was to determine the minimum lethal concentration (MLC of metronidazole in resistant and sensitive strains, as well as genetic patterns of these stains by PCR method. Methods: From February 2006 to March 2007, in a cross sectional study, clinical and wet mount examination of vaginal smear along with culture were performed on 683 women attending to public and private outpatient clinics in Hamadan. Trichomoniasis marked based on major clinical symptoms. Diagnosis confirmed using wet mount microscopically and culture in Diamond medium. A serial concentration of metronidazole was provided and all isolated Trichomonas strains (resistant and sensitive tested by standard method. Finally, all sensitive and resistant strains examined by PCR technique. Results: Only 15/683, (2.2% of patients clinically diagnosed trichomonal vaginitis were positive for T. vaginalis by wet smear and culture. The minimum lethal concentration (MLC for clinically sensitive isolates was 25 µg/ml; however, this concentration for resistant isolates was 200 µg/ml after 24 h and 100 µg/ml after 50 h. The results of PCR examination of DNA from sensitive and resistant isolates had same pattern. The lanes appeared by two primers were 98 bp and 261 bp for both clinically sensitive and resistant strains. Conclusion: Resistance to metronidazole in T. vaginalis has not relation to genetic variations and might be related to some physiologic pathways of organism.

  19. Assessing the loading and release of metronidazole from bacterial cellulose film as a pharmaceutical dressing

    Directory of Open Access Journals (Sweden)

    Mohammad Ali Salehi

    2017-08-01

    Full Text Available Background: Bacterial cellulose membrane (BCM produced by Gluconacetobacter xylinus is an advantageous bacterial product and because of its unique properties could be used as an ideal dressing. The aim of this study was to consider the capability of this biomaterial in the release of Metronidazole. In the case of proving this capability, it provides the basis for the production of a dressing containing this type of antibiotic. Materials and Methods: In this study, BCM was initially synthesized by Gluconacetobacter xylinus. The BCM was loaded by Metronidazole. Then the release process was considered in distilled water and buffer phosphate Saline. The ultra violet spectrophotometry was applied for measuring the concentration of the released drug. Results: The chemical structure of bacterial cellulose was confirmed by Fourier Transform Infrared (FT-IR spectroscopy. The release of Metronidazole in distilled water and phosphate buffered Saline was reached to 84.27% and 84.71%, respectively. Due to higher release in phosphate buffered Saline media, it seems that the trend of release in vitro provides efficient results. Conclusion: Results of this study provides the basis for future research on supplying an ideal dressing from this microbial product.

  20. Assessment of skin barrier function in rosacea patients with a novel 1% metronidazole gel.

    Science.gov (United States)

    Draelos, Zoe D

    2005-01-01

    The skin of patients with rosacea is extremely sensitive and hyper-reactive to dietary, environmental, and topical factors. Accordingly, the management of rosacea involves not only choosing appropriate medication and treatment for daily skin care, but also avoiding known trigger factors. Recently, 1% metronidazole, a mainstay of topical rosacea therapy, was reformulated in a gel vehicle that contains hydrosolubilizing agents (HSA) niacinamide, beta cyclodextrin, and a low concentration of propylene glycol. It is designed to solubilize greater concentrations of metronidazole than is possible in water alone while reducing the potential for irritation and barrier disruption. A 2-week study was undertaken by the author to evaluate the effect of the new 1% metronidazole gel on the skin barrier in 25 women with mild to moderate rosacea. Statistically significant improvement in disease severity, erythema, desquamation, and skin irritation was noted by the investigator by the end of week 1, which continued throughout the study. After 2 weeks, subjects noted improvements in skin condition and rosacea. Results of noninvasive assessments showed no disruption of the skin barrier. Furthermore, there was an increasing trend in skin hydration that approached statistical significance.

  1. [Giardia muris infection in laboratory rats (Rattus norvegicus) and treatment with metronidazole].

    Science.gov (United States)

    Beyhan, Yunus Emre; Hökelek, Murat

    2014-01-01

    This study was conducted to determine the effectiveness of metronidazole for treatment of Giardia muris infection in laboratory rats. The feces of rats was yellow watery diarrhea and brought to the surgery research center of University of Ondokuz Mayis in order to be a study. Stool samples were examined by native examination, evaluation of infection rates was done with an X40 lens, and results were recorded as positive from 1 to 4. Metronidazole was administered to infected animals orally for 5 days with a 20 mg/kg dose. As a result of fecal examination of 64 rats held in groups of four in cages, 15 of the cages (60 rats) were found to be infected with G. muris. While agents were not observed in collected stool samples following 5, 7, and 14 days of drug administration of 14 groups, trophozoite density in one cage was decreased (75%), and adverse effects were not seen in rats. Metronidazole was found to be an effective drug for the treatment of giardiasis.

  2. Entirely S-protected chitosan: A promising mucoadhesive excipient for metronidazole vaginal tablets.

    Science.gov (United States)

    Lupo, Noemi; Fodor, Benjamin; Muhammad, Ijaz; Yaqoob, Muhammad; Matuszczak, Barbara; Bernkop-Schnürch, Andreas

    2017-12-01

    Synthesis and evaluation of an entirely S-protected chitosan as mucoadhesive excipient for vaginal drug delivery. N-acetyl-cysteine was linked to 6-mercaptonicotinamide via disulphide exchange reaction. The obtained ligand, NAC-6-MNA, was subsequently attached to chitosan by carbodiimide mediated amide bond formation in two concentrations. The synthesized S-protected chitosan was chemically characterized and mucoadhesive properties and stability against oxidation were investigated. Moreover, metronidazole tablets comprising the S-protected chitosan were evaluated regarding water uptake capacity, disintegration behaviour, residence time on vaginal mucosa, release of the encapsulated drug and antimicrobial activity. S-protected chitosan displayed 160±19 (CS-MNA-160) and 320±38 (CS-MNA-320)µmol of ligand per gram of polymer. At pH 4.2, CS-MNA-160 and CS-MNA-320 showed 5.2-fold and 6.2-fold increase in mucus viscosity in comparison to unmodified chitosan (One-way ANOVA, pchitosan remained stable against oxidation in presence of 0.5%v/v hydrogen peroxide. Metronidazole tablets consisting in S-protected chitosan showed prolonged residence time on vaginal mucosa and improved water uptake capacity and disintegration time in comparison to tablets consisting of unmodified chitosan. Moreover, CS-MNA-320 metronidazole tablets displayed prolonged drug release and antimicrobial activity. On the basis of the achieved results, entirely S-protected chitosan represents a promising excipient for the development of metronidazole vaginal tablets. S-protected thiomers are polymers modified with thiol groups protected by aromatic ligands and characterized by strong mucoadhesive properties and high stability against oxidation. Up to date, the entirely S-protection of thiol groups was achieved via the synthesis of the ligand 2-((2-amino-2-carboxyethyl)disulfanyl)nicotinic acid) which can be directly bound to the backbone of polymers bearing carboxylic moieties as pectin. However, this

  3. Comparison of cefixime and amoxicillin plus metronidazole in the treatment of chronic periodontitis

    Directory of Open Access Journals (Sweden)

    Dukić Smiljka

    2016-01-01

    Full Text Available Introduction/Aim. Despite significant advances in current medicine and improvement of overall health education, chronic periodontitis is still a widespread disease. Losing teeth is the most serious complication of this particular illness. The aim of this study was to examine patients with chronic periodontitis in order to evaluate the efficacy of non-surgical therapy and combination of amoxicillin and metronidazole compared with cefixime, which has not been so far used for the treatment of this disease. Methods. Adult patients with chronic periodontitis (n = 90 underwent non-surgical periodontal treatment (zero-day and then randomly divided into three groups. The group I served as a control, the group II was additionally treated with the combination of amoxicillin and metronidazole (for 7 days, while the group III was treated with cefixime (also for 7 days. To assess the condition of periodontium before and seven days after the therapy, four clinical parameters were used: gingival index (GI, bleeding on probing (BOP, probing depth (PD and clinical attachment level (CAL. Results. On the day 7 after the beginning of the therapy, we found that all the three groups of patients had statistically significant clinical improvement of three parameters: GI, BOP and PD, but not of the CAL. However, the improvement of PD was only statistically, but not clinically significant. The improvement in the control group of patients on the day 7 was 19% in BOP and 28% in GI; this improvement was statistically highly significant after the addition of amoxicillin plus metronodazole (71% in BOP and 77% in GI or cefixime (62% in BOP and 82% in GI. Compared to the combination of amoxicillin and metronidazole, cefixim was statistically significantly more effective for GI (p < 0.05, while for the other three clinical parameters their effects were equal. Conclusion. The conjunction of amoxicillin plus metronidazole or cefixime to the causal treatment of patients with

  4. Fourteen-day high-dose esomeprazole, amoxicillin and metronidazole as third-line treatment for Helicobacter pylori infection.

    Science.gov (United States)

    Puig, Ignasi; González-Santiago, Jesús M; Molina-Infante, Javier; Barrio, Jesús; Herranz, Maria Teresa; Algaba, Alicia; Castro, Manuel; Gisbert, Javier P; Calvet, Xavier

    2017-09-01

    The efficacy of currently recommended third-line therapies for Helicobacter pylori is suboptimal, even that of culture-guided treatments. Resistance to multiple antibiotics is the major factor related to treatment failure. The aim of this study was to evaluate the effectiveness and safety of a 14-day therapy using high-dose of amoxicillin, metronidazole and esomeprazole. Multicenter open-label study as a register in routine clinical practice in patients with two previous failures of eradication therapy. A triple therapy with esomeprazole 40 mg b.d., amoxicillin 1 g t.d.s and metronidazole 500 mg t.d.s for 2 weeks was administered as a third-line therapy after a first treatment including clarithromycin and a second treatment including a quinolone. Helicobacter pylori status was determined by either histology or 13 C-UBT both before and after treatment. A total of 68 patients were included in this study. An interim analysis showed that only three out of eight patients who had received metronidazole in previous eradication regimens were cured (37%, 95% CI 8-75); as a result, after this interim analysis only metronidazole-naïve patients were included. The ITT eradication rate in metronidazole-naive patients was 64% (95% CI 51-76). Adverse events occurred in 58% of patients, all of them mild-to-moderate. Two patients (3%) did not complete >90% of the treatment because of side effects. No severe adverse events occurred. Cure rates of this 14-day schedule using high-dose esomeprazole, amoxicillin and metronidazole as a third-line eradication regimen were suboptimal, especially in patients who had received metronidazole in previous failed eradication regimens. © 2017 John Wiley & Sons Ltd.

  5. 5-Fluorouracil and 1-(2-chloroethyl)-3-cyclohexyl-1-nitrosourea (CCNU) followed by hydroxyurea, misonidazole, and irradiation for brain stem gliomas: a pilot study of the Brain Tumor Research Center and the Childrens Cancer Group

    International Nuclear Information System (INIS)

    Levin, V.A.; Edwards, M.S.; Wara, W.M.; Allen, J.; Ortega, J.; Vestnys, P.

    1984-01-01

    Twenty-eight evaluable children with the diagnosis of brain stem glioma were treated with 5-fluorouracil and CCNU before posterior fossa irradiation (5500 rads); during irradiation, the children received hydroxyurea and misonidazole. The treatment was well tolerated, and minimal toxicity was produced. The median relapse-free survival was 32 weeks, and the median survival was 44 weeks. Analysis of covariates showed that, in patients between the ages of 2 and 19 years, survival was longest in the older children (P less than 0.02). Tumor histology, sex, extent of operation (if any), Karnofsky score, and radiation dose did not correlate with survival

  6. Effects of hyperoxia on 18F-fluoro-misonidazole brain uptake and tissue oxygen tension following middle cerebral artery occlusion in rodents: Pilot studies.

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    Tim D Fryer

    Full Text Available Mapping brain hypoxia is a major goal for stroke diagnosis, pathophysiology and treatment monitoring. 18F-fluoro-misonidazole (FMISO positron emission tomography (PET is the gold standard hypoxia imaging method. Normobaric hyperoxia (NBO is a promising therapy in acute stroke. In this pilot study, we tested the straightforward hypothesis that NBO would markedly reduce FMISO uptake in ischemic brain in Wistar and spontaneously hypertensive rats (SHRs, two rat strains with distinct vulnerability to brain ischemia, mimicking clinical heterogeneity.Thirteen adult male rats were randomized to distal middle cerebral artery occlusion under either 30% O2 or 100% O2. FMISO was administered intravenously and PET data acquired dynamically for 3hrs, after which magnetic resonance imaging (MRI and tetrazolium chloride (TTC staining were carried out to map the ischemic lesion. Both FMISO tissue uptake at 2-3hrs and FMISO kinetic rate constants, determined based on previously published kinetic modelling, were obtained for the hypoxic area. In a separate group (n = 9, tissue oxygen partial pressure (PtO2 was measured in the ischemic tissue during both control and NBO conditions.As expected, the FMISO PET, MRI and TTC lesion volumes were much larger in SHRs than Wistar rats in both the control and NBO conditions. NBO did not appear to substantially reduce FMISO lesion size, nor affect the FMISO kinetic rate constants in either strain. Likewise, MRI and TTC lesion volumes were unaffected. The parallel study showed the expected increases in ischemic cortex PtO2 under NBO, although these were small in some SHRs with very low baseline PtO2.Despite small samples, the apparent lack of marked effects of NBO on FMISO uptake suggests that in permanent ischemia the cellular mechanisms underlying FMISO trapping in hypoxic cells may be disjointed from PtO2. Better understanding of FMISO trapping processes will be important for future applications of FMISO imaging.

  7. Clinical efficacy of Saccharomyces boulardii or metronidazole in symptomatic children with Blastocystis hominis infection.

    Science.gov (United States)

    Dinleyici, Ener Cagri; Eren, Makbule; Dogan, Nihal; Reyhanioglu, Serap; Yargic, Zeynel Abidin; Vandenplas, Yvan

    2011-03-01

    Although many Blastocystis infections remain asymptomatic, recent data suggest it also causes frequent symptoms. Therapy should be limited to patients with persistent symptoms and a complete workup for alternative etiologies. The goal of this study was to compare the natural evolution (no treatment) to the efficacy of Saccharomyces boulardii (S. boulardii) or metronidazole for the duration of diarrhea and the duration of colonization in children with gastrointestinal symptoms and positive stool examination for Blastocystis hominis. This randomized single-blinded clinical trial included children presenting with gastrointestinal symptoms (abdominal pain, diarrhea, nausea-vomiting, flatulence) more than 2 weeks and confirmed B. hominis by stool examination (B. hominis cysts in the stool with microscopic examination of the fresh stool). The primary end points were clinical evaluation and result of microscopic stool examination at day 15. Secondary end points were the same end points at day 30. Randomization was performed by alternating inclusion: group A, S. boulardii (250 mg twice a day, Reflor®) during 10 days; group B, metronidazole (30 mg/kg twice daily) for 10 days; group C, no treatment. At day 15 and 30 after inclusion, the patients were re-evaluated, and stool samples were examined microscopically. On day 15, children that were still symptomatic and/or were still B. hominis-infected in group C were treated with metronidazole for 10 days. There was no statistically significant difference between the three study groups for age, gender, and the presence of diarrhea and abdominal pain. On day 15, clinical cure was observed in 77.7% in group A (n, 18); in 66.6% in group B (n, 15); and 40% in group C (n:15) (p boulardii has potential beneficial effects in B. hominis infection (symptoms, presence of parasites). These findings challenge the actual guidelines.

  8. Preemptive warfarin dose reduction after initiation of sulfamethoxazole-trimethoprim or metronidazole.

    Science.gov (United States)

    Powers, Anna; Loesch, Erin B; Weiland, Anthony; Fioravanti, Nicole; Lucius, David

    2017-07-01

    To evaluate the utility of a preemptive warfarin dose reduction at the time of initiation of either sulfamethoxazole-trimethoprim or metronidazole, a retrospective chart review of patients who received an outpatient prescription for warfarin and either sulfamethoxazole-trimethoprim and/or metronidazole from July 1, 2011 to July 1, 2015 was conducted. Clinical outcomes compared Veterans who had a warfarin dose reduction and those who did not within 120 h (5 days) of antibiotic initiation. The primary outcome compared the pre-and post-antibiotic International Normalized Ratio (INR) of patients in the intervention group (warfarin dose reduction) with those in the control group (no intervention). Secondary outcomes assessed incidence of thromboembolic and major bleeding events within 30 days of antibiotic completion. Fifty patients were assessed. Forty-nine patients had at least one follow-up appointment; 126 follow-up visits were evaluated. There was a statistically significant difference for the change in therapeutic INR at the first follow-up appointment (p = 0.029) for those patients in the control group. On average, the patients in the intervention group required fewer follow-up visits (p = 0.019). There were no statistically significant differences for the overall rate of therapeutic INR values between groups, as well as no instances of a thromboembolic or major bleeding events during the follow-up period. Clinically significant differences were observed for patients who received a preemptive warfarin dose reduction upon initiation of sulfamethoxazole-trimethoprim or metronidazole. Patients in the intervention group required fewer follow-up appointments and were more likely maintain a therapeutic INR within the 30 days following the antibiotic course. Results of this study will be presented the at Pharmacy and Therapeutics committee in an effort to seek approval for policy development to initiate a local preemptive warfarin dose adjustment as a standard

  9. COMPARATIVE STUDY IN THE MANAGEMENT OF BACTERIAL VAGINOSIS METRONIDAZOLE VS. LACTOBACILLUS

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    Narmadha Selvaraj

    2017-01-01

    Full Text Available BACKGROUND The incidence and morbidity of bacterial vaginosis is high. But most of the patients are asymptomatic and recurrences are common even after effective treatment. Studies comparing the therapeutic efficacy of the drugs indicated for Bacterial vaginosis are also very minimal. Aim of this study was to analyse the epidemiological pattern of bacterial vaginosis and to compare the efficacy of Metronidazole and Lactobacillus in the management of bacterial vaginosis. MATERIALS AND METHODS 100 newly diagnosed Bacterial vaginosis patients were enrolled and randomly allotted into two study groups of Metronidazole for one week and Lactobacillus for two months respectively. The patients are followed up based on Amsel’s criteria and Nugent’s scoring system at the time of initiation of treatment, one week, one month, two months and six months after treatment. Ultrasonogram was done at the end of two months. Statistical Analysis- chi square test with yate’s correction and Fisher’s exact test (2 tailed to calculate the P value. Settings and Design- Prospective, open labeled, comparative clinical trial. RESULTS Lactobacillus group was better than Metronidazole based on Amsel’s criteria at six months follow up period and based on Nugent’s scoring system at two months and six months follow up period. CONCLUSION Epidemiological interpretation in our study shows Bacterial vaginosis is common in the 24-40 years of age; marital status, earlier age at marriage, number of deliveries is directly proportionate to bacterial vaginosis incidence. Irregular menstrual cycle, number of sexual partners, and mode of delivery has no association with the incidence of Bacterial vaginosis. Moderate to profuse genital discharge is the commonest symptom observed. Whiff test (80%, Clue cells (90% and alkaline vaginal pH > 5 has high degree of sensitivity.

  10. The Combination of Fosfomycin, Metronidazole, and Recombinant Human Granulocyte-Macrophage Colony-Stimulating Factor is Stable in vitro and Has Maintained Antibacterial Activity

    DEFF Research Database (Denmark)

    Fonnes, Siv; Holzknecht, Barbara Juliane; Gasbjerg, Lærke Smidt

    2017-01-01

    to the antibacterial effects of fosfomycin and metronidazole alone. CONCLUSION: The drug combination had neutral and stable pH, was iso-osmotic, and had stable concentrations during 24 h of storage. The antibacterial effect of fosfomycin and metronidazole were not altered when the drugs were mixed....

  11. INFLUENCE OF METRONIDAZOLE, CO, CO2, AND METHANOGENS ON THE FERMENTATIVE METABOLISM OF THE ANAEROBIC FUNGUS NEOCALLIMASTIX SP STRAIN L2

    NARCIS (Netherlands)

    MARVINSIKKEMA, FD; REES, E; KRAAK, MN; GOTTSCHAL, JC; PRINS, RA

    The effects of metronidazole, CO, methanogens, and CO, on the fermentation of glucose by the anaerobic fungus Neocallimastix sp. strain L2 were investigated. Both metronidazole and CO caused a shift in the fermentation products from predominantly H-2, acetate, and formate to lactate as the major

  12. Efficacy of metronidazole versus placebo in pain control after hemorrhoidectomy: results of a controlled clinical trial

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    Sergio Solorio-López

    2015-11-01

    Full Text Available Introduction: Hemorrhoidal disease occurs in 50% of people aged > 40 years and is the most common reason for anorectal surgery. Pain is the main complication. Multiple topical and systemic drugs have been investigated for pain control, but there is no ideal treatment. Metronidazole has been shown to decrease postoperative pain but is not used widely. Objective: To evaluate the effect of oral metronidazole versus placebo and to assess postoperative pain following hemorrhoidectomy. Material and methods: Controlled clinical trial in adult patients who underwent elective hemorrhoidectomy for grade III/IV hemorrhoids. Patients were assigned to receive metronidazole (500 mg q8 h orally; study group, SG or placebo (control group, CG for 7 days after surgery. Pain was assessed using a visual analog scale after surgery. Analgesic administration (time and use of analgesics and resumption of daily life activities were also assessed. Results: Forty-four patients were included, 22 in each group. Postoperative pain differed significantly between the SG and CG at 6 h (3.86 ± 0.56, 6.64 ± 1.49, 12 h (5.59 ± 1.33, 8.82 ± 0.79, 24 h (6.86 ± 1.49, 9.73 ± 0.45, day 4 (5.32 ± 2.10, 9.50 ± 0.59, day 7 (3.14 ± 1.03, 7.36 ± 1.39, and day 14 (2.14 ± 0.46, 5.45 ± 1.29. The first analgesia dose was required at 21.27 ± 5.47 h in the CG and 7.09 ± 2.36 h in the SG (p < 0.05, the time of analgesic use was 6.86 ± 1.61 days in the CG and 13.09 ± 2.48 days in the SG (p < 0.05, and resumption of daily activities occurred at 7.59 ± 1.56 days in the CG and 14.73 ± 3.76 days in the SG (p < 0.05. Conclusion: Oral administration of metronidazole is effective in pain management after hemorrhoidectomy.

  13. Radiosensitizing efficacy of iso-metronidazole after intravesical application in bladder cancer. A clinical phase II study

    International Nuclear Information System (INIS)

    Kob, D.; Lilienthal, A.; Bauhardt, H.; Merkle, K.; Schroeder, E.; Schroeder, E.; Hentschel, M.

    1991-01-01

    The radiosensitizing efficacy of iso-Metronidazole, a 4-Nitroimidazole derivative, was evaluated in a prospective clinical phase II study. The results of combined radiotherapy of 25 patients with bladder cancer were compared with those of a control group of 25 patients treated with radiotherapy only. Tumor regression six months after radiotherapy was used as an endpoint. The surgical procedure was performed as double TUR. Evaluating the local tumor control after additional application of iso-Metronidazole a gain factor of 1.2 is obtained. (orig.) [de

  14. Efficacy of drugs against Giardia muris in mice Mus musculus naturally infected/ Eficácia de drogas contra Giardia muris em camundongos Mus musculus naturalmente infectados

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    Silvia Gonzalez Monteiro

    2008-08-01

    Full Text Available This study aimed to evaluate the efficacy of metronidazole, fenbendazole and secnidazole against Giardia muris in mice naturally infected. Forty mice of the species Mus musculus were divided in four groups of ten each, being group A non treated, the control group and groups B, C and D treated with 4mg/ml of metronidazole, fenbendazole and secnidazole, respectively. Two feces collection, on day 0 and on day 10 after treatment, were done in order to evaluate the efficacy of the drugs. Samples were analyzed by the centrifugal-flotation method with zinc sulfate. Efficacy of 97,05% for metronidazole, 98,30% for fenbendazole and 100% for secnidazole were observed in the study. According to the results it was concluded that the tested drugs were effective for the treatment of mice parasitized by Giardia muris.Este estudo visou avaliar a eficácia do metronidazol, fenbendazole e secnidazol contra Giardia muris em camundongos naturalmente infectados. Foram utilizados 40 camundongos da espécie Mus musculus divididos em quatro grupos de 10 animais cada, sendo grupo A, grupo controle, não tratados, e grupos B, C e D tratados com 4mg/ml de metronidazol, fenbendazole e secnidazol, respectivamente. Para avaliar a eficácia dos medicamentos foram realizadas duas coletas de fezes uma no dia zero e outra 10 dias após tratamento. As amostras foram processadas e analisadas a partir do método de centrífugo-flutuação com sulfato de zinco. No estudo observou-se eficácia de 97,05% para metronidazol, 98,30% para fenbendazole e 100% para secnidazol no tratamento de giardiase murina. Com base nos resultados concluí-se que as drogas testadas apresentaram eficácia no tratamento de camundongos parasitados por Giardia muris.

  15. Clinical evaluation of an ointment with 10% metronidazole and 2% lidocaine in the treatment of alveolitis.

    Science.gov (United States)

    Silva, L J; Poi, W R; Panzarini, S R; Rodrigues, T S; Simonato, L E

    2006-01-01

    In this study, the authors evaluate the use of a 10% metronidazole and 2% lidocaine ointment, using a lanolin base and mint as flavoring, to treat alveolitis in humans. Twenty-five patients, with a diagnosis of alveolitis, were treated in the following way: locoregional anesthesia; surgical cleaning of the socket with alveolar curettes; saline solution irrigation with a 20 ml disposable syringe; and complete filling of the socket with the ointment. The analysis of the results showed that the painful symptoms were severe before and on the day of the treatment in 17 (68%) of the 25 patients treated. Post-treatment analysis presented 2 patients (18%) with severe painful symptoms after 24 h of the treatment and complete remission of painful symptoms after 48 h of the treatment with the ointment. Based on the results, it is possible to conclude that the 10% metronidazole and 2% lidocaine ointment, with mint flavoring and lanolin as a base, can be used to treat alveolitis.

  16. Nonsurgical therapy of chronic periodontitis with adjunctive systemic azithromycin or amoxicillin/metronidazole.

    Science.gov (United States)

    Jentsch, Holger F R; Buchmann, Andreas; Friedrich, Abel; Eick, Sigrun

    2016-09-01

    The objective of the present study is to compare the effect of systemic adjunctive use of azithromycin with amoxicillin/metronidazole to scaling and root planing (SRP) in a clinical study. Data from 60 individuals with chronic periodontitis were evaluated after full-mouth SRP. Antibiotics were given from the first day of SRP, in the test group (n = 29), azithromycin for 3 days and, in the control group (n = 31), amoxicillin/metronidazole for7 days. Probing depth (PD), attachment level (AL), and bleeding on probing (BOP) were recorded at baseline and after 3 and 12 months. Gingival crevicular fluid was analyzed for matrix metalloprotease (MMP)-8 and interleukin (IL)-1beta levels. Subgingival plaque was taken for assessment of the major bacteria associated with periodontitis. In both groups, PD, AL, and BOP were significantly reduced (p chronic periodontitis; however, a randomized placebo-controlled multicenter study is needed. Application of azithromycin as a single antibiotic for 3 days might be considered as an additional adjunctive antibiotic to SRP in selected patients.

  17. Microcalorimetric determination of the effects of amoxicillin, metronidazole, and their combination on in vitro biofilm.

    Science.gov (United States)

    Astasov-Frauenhoffer, Monika; Braissant, Olivier; Hauser-Gerspach, Irmgard; Weiger, Roland; Walter, Clemens; Zitzmann, Nicola U; Waltimo, Tuomas

    2014-02-01

    The mechanism of action of adjuvant antibiotic therapy in the treatment of peri-implantitis is not well understood. The aim of this study is to investigate antibiotic susceptibility of an in vitro biofilm by isothermal microcalorimetry (IMC). Titanium disks containing a 72-hour three-species biofilm (Streptococcus sanguinis DSM20068, Fusobacterium nucleatum ATCC10953, and Porphyromonas gingivalis DSM20709) were placed in a series of IMC ampoules with nutrient agar supplemented with increasing concentrations of amoxicillin, metronidazole, or their combination and incubated anaerobically for 10 days. Lag time and maximum growth rate were determined from continuous heat-flow recordings of metabolic activity. To validate the IMC biofilm results, adherent S. sanguinis and P. gingivalis were incubated anaerobically in medium supplemented with antibiotics at 37°C for 24 hours, and their vitality was determined by live/dead staining, conventional culturing, and IMC. In all biofilm samples incubated with antibiotics, a prolonged lag phase was observed compared with controls (P live/dead staining and conventional culturing. IMC gives new evidence about antibiotic effects on oral biofilms and is more informative than conventional culture and live/dead assays. The combination of antibiotics was found to be more efficient than metronidazole alone; however, only minor differences in growth inhibition were detected compared with amoxicillin alone.

  18. The Prevalence of Trichomoniasis and Metronidazole Susceptibility of the Isolates in Ghorveh City, Year 2015

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    Mohammad Matini

    2016-11-01

    Full Text Available Introduction: Trichomoniasis is one of the most common non-viral sexually transmitted diseases caused by Trichomonas vaginalis. The aim of this study was to determine the prevalence of the infection and to consider the metronidazole susceptibility of the T. vaginalis isolates. Methods:This cross sectional study was conducted on 670females attending gynecology clinics of Qorveh city, Kurdistan province, during year 2015. Diagnosis of trichomoniasis was performed using Dorset culture medium and wet mount methods. In vitro drug susceptibility testing was done aerobically after establishment of the isolates in an axenic culture medium, diamond. Results: From 670vaginal samples, eight %1.2(and four %0.6(were positive for T. vaginalis by wet mount and culture methods, respectively. Fifty percent of the infected individuals were aged from 35to 44years old and were illiterate P < 0.05(. Clinical signs and symptoms of trichomoniasis were vaginal discharge, itching, burning sensation, dyspareunia, abdominal pain and greenish discharge. All of the parasites were sensitive to metronidazole with mean minimum inhibitory concentration MIC(and standard deviation of 1.9and 0.85µg/mL, respectively. Conclusions:Although, the prevalence of trichomoniasis is relatively low in the studied population but due to the importance of sexually transmitted diseases in public health, strategic measurements are necessary to prevent and control the infection.

  19. Development and validation of HPLC analytical method for quantitative determination of metronidazole in human plasma

    International Nuclear Information System (INIS)

    Safdar, K.A.; Shyum, S.B.; Usman, S.

    2016-01-01

    The objective of the present study was to develop a simple, rapid and sensitive reversed-phase high performance liquid chromatographic (RP-HPLC) analytical method with UV detection system for the quantitative determination of metronidazole in human plasma. The chromatographic separation was performed by using C18 RP column (250mm X 4.6mm, 5 meu m) as stationary phase and 0.01M potassium dihydrogen phosphate buffered at pH 3.0 and acetonitrile (83:17, v/v) as mobile phase at flow rate of 1.0 ml/min. The UV detection was carried out at 320nm. The method was validated as per the US FDA guideline for bioanalytical method validation and was found to be selective without interferences from mobile phase components, impurities and biological matrix. The method found to be linear over the concentration range of 0.2812 meu g/ml to 18.0 meu g/ml (r2 = 0.9987) with adequate level of accuracy and precision. The samples were found to be stable under various recommended laboratory and storage conditions. Therefore, the method can be used with adequate level of confidence and assurance for bioavailability, bioequivalence and other pharmacokinetic studies of metronidazole in human. (author)

  20. Fast and sensitive metronidazole determination by means of voltammetry on renewable amalgam silver based electrode without the preconcentration step

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    Piech Robert

    2017-01-01

    Full Text Available Application of cyclic renewable amalgam silver-based electrode (Hg(AgFE for sensitive metronidazole detection by the differential pulse voltammetry (DPV is described. The unique properties of the Hg(AgFE such as the relative large surface area and its fast and very simple renewal were fully utilized for sensitive measurements. Compared with the classical hanging mercury drop electrode (HMDE, the renewable Hg(AgFE significantly increases the reduction peak current of metronidazole because of its large surface area. The effects of various factors for the metronidazole determination such as: pulse height and width, step potential, surface area of the working electrode, and basic electrolyte composition are optimized. The obtained calibration graph is linear from 0.1 (17 μg L-1 to 2 μM (342 μg L-1 with correlation coefficient 0.999. For the Hg(AgFE with the surface area of 10.1 mm2 the limit of detection (LOD is 20 nM (3.4 μg L-1. The repeatability of the method at a concentration of the analyte of 0.5 μM (5.6 μg L−1, expressed as relative standard deviation (RSD is 2.1 % (n = 7. The proposed method was successfully applied and confirmed by studying recovery of metronidazole from spiked samples.

  1. The influence of metronidazole resistance on the efficacy of ranitidine bismuth citrate triple therapy regimens for Helicobacter pylori infection

    NARCIS (Netherlands)

    Van der Wouden, EJ; Thijs, JC; Van Zwet, AA; Kooy, A; Kleibeuker, JH

    Aim: To assess the influence of metronidazole resistance on the efficacy of ranitidine bismuth citrate-based triple therapy regimens in two consecutive studies. Methods: In the first study, patients with a culture-proven Helicobacter pylori infection were treated with ranitidine bismuth citrate 400

  2. Bismuth-Based Quadruple Therapy with Bismuth Subcitrate, Metronidazole, Tetracycline and Omeprazole in the Eradication of Helicobacter pylori

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    Raymond Lahaie

    2001-01-01

    Full Text Available BACKGROUND: A previous study showed that 14 days of qid bismuth-based triple therapy with tetracycline 500 mg, metronidazole 250 mg and colloidal bismuth subcitrate 120 mg resulted in excellent Helicobacter pylori eradication rates (89.5%. The present study looked at a shorter treatment period by adding omeprazole and by reducing the dose of tetracycline.

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

    Science.gov (United States)

    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. Copyright © 2015 Elsevier Ltd. All rights reserved.

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

    Science.gov (United States)

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

    2015-01-01

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

  5. Drug susceptibility testing in microaerophilic parasites: Cysteine strongly affects the effectivities of metronidazole and auranofin, a novel and promising antimicrobial

    Directory of Open Access Journals (Sweden)

    David Leitsch

    2017-12-01

    Full Text Available The microaerophilic parasites Entamoeba histolytica, Trichomonas vaginalis, and Giardia lamblia annually cause hundreds of millions of human infections which are treated with antiparasitic drugs. Metronidazole is the most often prescribed drug but also other drugs are in use, and novel drugs with improved characteristics are constantly being developed. One of these novel drugs is auranofin, originally an antirheumatic which has been relabelled for the treatment of parasitic infections. Drug effectivity is arguably the most important criterion for its applicability and is commonly assessed in susceptibility assays using in vitro cultures of a given pathogen. However, drug susceptibility assays can be strongly affected by certain compounds in the growth media. In the case of microaerophilic parasites, cysteine which is added in large amounts as an antioxidant is an obvious candidate because it is highly reactive and known to modulate the toxicity of metronidazole in several microaerophilic parasites.In this study, it was attempted to reduce cysteine concentrations as far as possible without affecting parasite viability by performing drug susceptibility assays under strictly anaerobic conditions in an anaerobic cabinet. Indeed, T. vaginalis and E. histolytica could be grown without any cysteine added and the cysteine concentration necessary to maintain G. lamblia could be reduced to 20%. Susceptibilities to metronidazole were found to be clearly reduced in the presence of cysteine. With auranofin the protective effect of cysteine was extreme, providing protection to concentrations up to 100-fold higher as observed in the absence of cysteine. With three other drugs tested, albendazole, furazolidone and nitazoxanide, all in use against G. lamblia, the effect of cysteine was less pronounced. Oxygen was found to have a less marked impact on metronidazole and auranofin than cysteine but bovine bile which is standardly used in growth media for G

  6. The use of immobilized form of benzalkonium chloride and metronidazole in the treatment of purulent wounds

    Directory of Open Access Journals (Sweden)

    Anastasia S. Gorohova

    2017-01-01

    Full Text Available The purpose of the study is to investigate the wound-healing effect of the immobilized form of benzalkonium chloride and metronidazole based on the sodium salt of carboxymethylcellulose (Na-CMC or polyethylene oxide (PEO in the treatment of an experimental purulent wound.Materials and methods. The following compositions were studied, %. Combination 1: benzalkonium chloride – 0.02; Metronidazole – 1,0; Sodium carboxymethylcellulose (NaCMC – 4,0; Purified water – up to 100,0. Combination 2: benzalkonium chloride – 0,02; Metronidazole – 1,0; Polyethylene oxide, m. 400 – 80.0; Polyethylene oxide, m. 1500 – 20,0. The experiment was performed on 180 male Wistar rats, which were divided into three statistically homogeneous groups of 60 animals in each, a purulent wound was modeled in all experimental rats using the method of P.I. Tolstykh. In the control group local treatment of the wound was performed with the help of “Levomekol” ointment, in two experimental groups, the combination was treated with 1 and 2.The course evaluation of the wound process was carried out using planimetric, microbiological and histological methods of investigation. The data were recorded and the animals were eliminated from the experiment on the 1st, 3rd, 5th, 8th, 10th and 15th days.Results. The data of the microbiological study confirmed the high efficiency of the combinations developed by the authors in relation to standard test strains of pathogen microorganisms. As a result of the planimetric study, a significant decrease in the area of wounds in the experimental group 1 was found compared to the ontrol group, which indicates a more effective course of the healing process in experimental group 1. The same process was noted in the experimental group 2, starting from the 5th day of observation relative to the Control. The use of combinations developed by the authors in the treatment of the purulent-inflammatory process of the subcutaneous layer

  7. Treatment of vaginal infections: effectiveness of the association of metronidazole and clotrimazole

    Directory of Open Access Journals (Sweden)

    Simone Ferrero

    2010-03-01

    Full Text Available The normal vagina of women of reproductive age is colonised by lactobacilli that produce lactic acid, hydrogen peroxide and bacteriocins; these substances contribute to lowering the vaginal pH. A low vaginal pH creates an environment hostile to the growth of other microrganisms. When the number of lactobacilli is decreased, the resulting increase in the pH may favour vaginal infections. The three most common vaginal infections are bacterial vaginosis, trichomoniasis, and vaginal candidosis. There are multiple clinical and laboratory tests for diagnosing vaginal infections; the most commonly used methods for diagnosing bacterial vaginosis are the Amsel’s criteria and the Nugent’s Gram stain scale. Infections caused by Candida and Trichomonas vaginalis can be diagnosed by microscopic examination of vaginal secretions. Clotrimazole and metronidazole, especially when administered topically, are highly effective in treating vaginal infections.

  8. PDGF-metronidazole-encapsulated nanofibrous functional layers on collagen membrane promote alveolar ridge regeneration

    Directory of Open Access Journals (Sweden)

    Ho MH

    2017-08-01

    Full Text Available Ming-Hua Ho,1 Hao-Chieh Chang,2,3 Yu-Chia Chang,3 Jeiannete Claudia,1 Tzu-Chiao Lin,2 Po-Chun Chang2,3 1Department of Chemical Engineering, College of Engineering, National Taiwan University of Science and Technology, Taipei, Taiwan; 2Graduate Institute of Clinical Dentistry, School of Dentistry, National Taiwan University, Taipei, Taiwan; 3Department of Dentistry, National Taiwan University Hospital, Taipei, Taiwan Abstract: This study aimed to develop a functionally graded membrane (FGM to prevent infection and promote tissue regeneration. Poly(L-lactide-co-D,L-lactide encapsulating platelet-derived growth factor (PDLLA-PDGF or metronidazole (PDLLA-MTZ was electrospun to form a nanofibrous layer on the inner or outer surface of a clinically available collagen membrane, respectively. The membrane was characterized for the morphology, molecule release profile, in vitro and in vivo biocompatibility, and preclinical efficiency for alveolar ridge regeneration. The PDLLA-MTZ and PDLLA-PDGF nanofibers were 800–900 nm in diameter, and the thicknesses of the functional layers were 20–30 µm, with sustained molecule release over 28 days. All of the membranes tested were compatible with cell survival in vitro and showed good tissue integration with minimal fibrous capsule formation or inflammation. Cell proliferation was especially prominent on the PDLLA-PDGF layer in vivo. On the alveolar ridge, all FGMs reduced wound dehiscence compared with the control collagen membrane, and the FGM with PDLLA-PDGF promoted osteogenesis significantly. In conclusion, the FGMs with PDLLA-PDGF and PDLLA-MTZ showed high biocompatibility and facilitated wound healing compared with conventional membrane, and the FGM with PDLLA-PDGF enhanced alveolar ridge regeneration in vivo. The design represents a beneficial modification, which may be easily adapted for future clinical use. Keywords: tissue engineering, platelet-derived growth factor, metronidazole, alveolar process

  9. Clinical experience of using metronidazole as an external therapy of acne

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    A. V. Statsenko

    2014-01-01

    Full Text Available Metrogyl gel for external use (metronidazole 1% has an antioxidant activity and substantially reduces the production of active oxygen compounds by neutrophilic leukocytes in the skin. A combination therapy of light to moderate acne with the use of external retinoids and metronidazole can be more efficient than a monotherapy with the use of these drugs alone. Goal. To assess the clinical efficacy, safety and tolerability of Metrogyl gel for external use in a combination with Klenzit gel (adapalene 0.1% for treatment of patients with acne vulgaris. Materials and methods. The authors conducted an open-label controlled study of the efficacy, safety and tolerability of Metrogyl gel for external use in a combination with Klenzit gel for external use. As many as 50 patients suffering from acne vulgaris took part in the study, which lasted for eight weeks. The subjects were subdivided into two groups: combination therapy (Group 1, n = 15 and monotherapy with the use of external retinoids (Group 2, n = 15. Results. Adverse effects such as dry skin and peeling were observed among the patients from Group 1 less often (by 3.3 times - 5/35 (14.3% of cases than in Group 2 (7/15 (46.7% of cases (p = 0.036. The total share of acne patients with clinical recovery and substantial improvement in Group 1 was 33/35 (94.3%, which is 41.4% as much as in Group 2 (10/15 (66.7% (p = 0.033. Conclusions. A combination of Metrogyl gel and external retinoids is more efficient than a monotherapy with the use of topical retinoid alone, and such a therapy demonstrates higher tolerability.

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

    Science.gov (United States)

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

    2014-07-01

    Metronidazole may be of use in the treatment of infectious mononucleosis (IM). Our aim is to show that metronidazole shortens hospital stay for patients with severe IM. A single-centre randomized controlled trial was undertaken in patients admitted with severe IM, who were with a similar group treated by the standard care. Patients were blinded to which treatment arm they were in. Forty-two of these patients were enrolled in the trial. The primary endpoint was the difference in length of stay. This was significantly less in the metronidazole group (3.67 days v 4.67) (p 0.032). This study demonstrates that metronidazole has a role to play in severe infectious mononucleosis. © 2013 The Authors Clinical Microbiology and Infection © 2013 European Society of Clinical Microbiology and Infectious Diseases.

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

    Science.gov (United States)

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

    2015-09-01

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

  12. Quantitative analysis of fluorodeoxyglucose-, fluoro-misonidazole- and fluoro-thymidine-PET images on five patients irradiated for a non-small-cell bronchial cancer; Analyse quantitative d'images de TEP au fluorodesoxyglucose, au fluoromisonidazole et a la fluorothymidine chez cinq patients irradies pour un cancer bronchique non a petites cellules

    Energy Technology Data Exchange (ETDEWEB)

    Thureau, S.; Dubray, B. [Departement de radiotherapie et physique medicale, centre Henri-Becquerel, Rouen (France); Litis EA 4108, QuantiF, universite de Rouen, Rouen (France); Modzelewski, R.; Lelandais, B.; Edet Sanson, A.; Gardin, I.; Vera, P. [Litis EA 4108, QuantiF, universite de Rouen, Rouen (France); Departement de medecine nucleaire, centre Henri-Becquerel, Rouen (France)

    2011-10-15

    As fluorodeoxyglucose-PET (positron emission tomography) is used for the planning of non-small-cell bronchial carcinoma radiotherapy in order to help to define the gross tumour volume (GTV), and as new tracers have been developed to define a biological target volume, the authors report the comparison of several thresholding methods by using fluorodeoxyglucose-, fluoro-misonidazole- and fluoro-thymidine-PET images. They notice important differences between the delineated volumes. Short communication

  13. The effect of irritant dermatitis on cutaneous bioavailability of a metronidazole formulation, investigated by microdialysis and dermatopharmacokinetic method

    DEFF Research Database (Denmark)

    Ortiz, P.G.; Hansen, S.H.; Shah, V.P.

    2008-01-01

    Background: Determination of drug penetration in diseased skin represents a challenge. Objective: To compare dermal microdialysis and tape-strip sampling of drug penetration in normal skin and skin with irritant dermatitis. Methods: The two methodologies were employed simultaneously in 16 healthy...... methods. Results: Microdialysis showed a significant threefold increase in metronidazole penetration in skin with irritant dermatitis compared with unmodified skin. Conversely, the concentration of metronidazole in tape-strip samples was significantly decreased in irritant dermatitis. Conclusion......: The selection of sampling methodology should be based on the skin layer of interest as well as the integrity of the skin barrier. Whenever the dermal tissue is the target for topical treatment, microdialysis sampling should be the method of choice Udgivelsesdato: 2008...

  14. Solid-State FTIR Spectroscopic Study of Two Binary Mixtures: Cefepime-Metronidazole and Cefoperazone-Sulbactam

    Directory of Open Access Journals (Sweden)

    Hassan Refat H. Ali

    2017-01-01

    Full Text Available The structural information of the pharmaceuticals and insights on the modes of molecular interactions are very important aspects in drug development. In this work, two cephalosporins and antimicrobial combinations, cefepime-metronidazole and cefoperazone-sulbactam, were studied in the solid state using FTIR spectroscopy for the first time. Quantitation of the studied drugs and their binary mixtures was performed by integrating the peak areas of the characteristic well-resolved bands: υ (C=O band at 1773 cm−1 for cefepime and ring torsion band at 826 cm−1 for metronidazole and υ (C=O band at 1715 cm−1 for cefoperazone and ring torsion band at 1124 cm−1 for sulbactam. The results of this work were compared with the relevant spectrophotometric reported methods. This study provides data that can be used for the preparative process monitoring of the studied drugs in various dosage forms.

  15. Contaminated fistula following J-pouch ileoanal reservoir. Treatment with a collagen sponge containing gentamicin and metronidazole. Case report

    DEFF Research Database (Denmark)

    Nielsen, R; Bülow, Steffen; Moesgaard, F

    1991-01-01

    In a 55-year-old woman, a 1 x 5 cm fistula developed in the ileoanal anastomosis after restorative proctocolectomy with J-pouch ileoanal reservoir and temporary ileostomy for intractable ulcerative colitis. The fistula extended between the pouch and the sacral bone. Lasting closure was achieved b...... by intrafistular placement of a collagen sponge containing gentamicin and soaked in metronidazole solution and pouch drainage through a transanal Foley catheter....

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

    Science.gov (United States)

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

    2016-12-01

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

  17. Effect of combined radiotherapy, hyperthermia, radioprotective agent and hypoxic cell sensitizer on mice testes

    Energy Technology Data Exchange (ETDEWEB)

    Nakano, Yasuhiko

    1985-08-01

    Application of hyperthermia was executed by immersing pelvis, testes and legs of mice in a thermostatically controlled water bath. Irradiation was carried out using Toshiba KXC-18 type X-ray therapy machine. Mice were killed 30 days after treatment. The testis weights obtained after hypertheramia alone were compared with that of the control and the relative testis weight ratios were calculated. The testis weights of mice treated for 5, 10, 20 and 40 min. in 40 deg C water and for 5 and 10 min. in 43 deg C water were not significantly different from the control. Their weights were reduced when treated for 20 min. in 43 deg C water and for 5 min. in 46 deg C water and their testis weight ratios were 0.81 and 0.46, respectively. The testis weights of irradiated mice decreased to about 45 % of the control at 250 rad. Beyond this dose, reduction of their weights was slowed down and testis weight at 1,000 rad was 28 %. There was not significantly difference between the relative testis weight ratios of the irradiation alone and that of the radiotherapy combined with YM-08310 (S-2-)3-aminopropylamino) ethyl phosphorothioic acid monohydrate). But when hyperthermia was added to their treatment, the effectiveness of the YM-08310 was slightly increased. The relative testis weight ratio on 400 rad X-ray combined with YM-08310 was 0.32 of the control, while its ratio on the radiotherapy and YM-08310 combined with the hyperthermia (43 deg C, 10 min.) was 0.43. (p < 0.01). The misonidazole treatments at 50, 100 and 200 rads were found to be effectuve. Radiation alone gave the relative testis weight ratios of 0.78, 0.71 and 0.49, respectively. In contrast, its ratios on the irradiation combined with the misonidazole were 0.57 (p < 0.01), 0.46 (p < 0.01) and 0.41 (p < 0.001). But, the additional hyperthermia combined with their treatment was found to be ineffective. (J.P.N.).

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

    Directory of Open Access Journals (Sweden)

    Annamaria Buschini

    2009-01-01

    Full Text Available 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.

  19. Studies of metronidazole radiosensitizing effect in radiation treatment of patients with oral cavity cancer

    International Nuclear Information System (INIS)

    Polyakov, P.Yu.; Daryalova, S.L.; Pelevina, I.I.; Karakulov, R.K.; Zel'vin, B.M.; Kiseleva, E.S.; Kvasov, V.A.

    1985-01-01

    Clinical observations of 26 patients with tongue, oral cavity and oropharyngeal cancer receiving telegammatherapy by dynamic dose fractionation scheme in combination with metronidazole (MZ), and of 38 patients from the control group treated using the identical schedule without MZ suggest that MZ favors increasing radiation damage in tumors in those sites without changing the character or intensifying early radiation reactions. After oral administration of MZ in single doses of 5-6 g/m 2 it reached its maximum in the blood serum within 2-4 h. When the total dose of 30-60 g of MZ was used, a marked toxic effect manifest in gastrointestinal symptoms was observed in 33.3% of patients. MZ has a negative effect on liver functions; however, changes in biochemical tests were reversible and within normal values. Simultaneous studies of biopsy material from 22 patients (11 from each group) in terms of proliferation activity showed that oral cavity tumors contain a significant portion of proliferating cells which notably decrease in the course of radiation therapy. The decrease is marked to a greater extent after irradiation in combination with MZ. (author)

  20. Albendazole versus metronidazole in the treatment of adult giardiasis: a randomized, double-blind, clinical trial.

    Science.gov (United States)

    Cañete, Roberto; Rodríguez, Pablo; Mesa, Lumey; Brito, Katia; Prior, Ada; Guilhem, Dirce; Novaes, M R C G

    2012-01-01

    Albendazole (ABZ) is a benzimidazole carbamate compound currently in use for human medical practice against enterobiasis and soil-transmitted helminthiasis (STH); However, its spectrum of activity is broad and goes beyond these infections. This study compares the efficacy and safety of ABZ versus metronidazole (MTZ) in human giardiasis. A randomized, double-blind, clinical trial was carried out at the Centre of Hygiene, Epidemiology and Microbiology in Matanzas City, Cuba. Adult patients with confirmed symptomatic G. duodenalis mono-infection were randomly assigned to receive either ABZ [400 mg daily (n = 75)] or MTZ [250 mg t.i.d. (n = 75)], both for 5 days. Follow-up fecal samples were obtained at 3, 5, 7 days after treatment end. The efficacy was similar for both treatment groups: ABZ (82.6%) and MTZ (85.3%); p > 0.05. Side-effects including bitter taste, headache, vomiting and dizziness were significantly higher in the MTZ group. Abdominal pain was significantly higher in ABZ group. ABZ was found as effective as MTZ in the treatment of G. duodenalis infections in adult patients from Cuba and could be a useful drug in areas where co-infection with STH infections is common.

  1. Preparation and characterization of poly(vinyl alcohol) hydrogel contain metronidazole by irradiation

    Energy Technology Data Exchange (ETDEWEB)

    Baik, Jae; Park, Jong Seok; Jeong, Jin Oh; Jeong, Sung In; Gwon, Hui Jeong; Ahn, Sung Jun; Lim, Youn Mook [Advanced Radiation Technology Institute, Korea Atomic Energy Research Institute, Jeongeup (Korea, Republic of)

    2016-11-15

    Periodontitis is disease of damaged gum tissue that is not removed the plaque onto teeth. In case that the symptoms of disease get pain worse, it will have to extract tooth because of tumefy or bleeding at gums so treatment of drug was required to periodontitis. In this study, the hydrogel was prepared by including superior viscous, excellent elastic, and biocompatibility of Poly(vinyl alcohol, PVA) and antimicrobial drug of Metronidazole (MD). The 15 wt% PVA was dissolved in deionized water and then prepared PVA solution was irradiated using gamma-ray at 25 kGy (10 kGy hr{sup -1}). In addition, PVA hydrogel was immersed in each 0.1, 0.25 and 0.5 wt% MD solution using stirrer for 24 hr. The result of the gelation, 0.5 wt% MD loaded PVA hydrogel (76%) was lower than PVA hydrogel (88.2%). The swelling ration of 0.5 wt% MD loaded PVA hydrogel (294.8%) was higher than PVA hydrogel (105.2%). The compressive strength and thermal properties of MD loaded PVA hydrogel was gradually lower. The drug release test of 0.5 wt% MD loaded PVA hydrogel (61%) was higher than 0.1 wt% MD loaded PVA hydrogel (12%). Therefore, MD loaded PVA hygrogel may be a promising tool for periodontitis medicine by gamma-ray.

  2. Preparation and characterization of poly(vinyl alcohol) hydrogel contain metronidazole by irradiation

    International Nuclear Information System (INIS)

    Baik, Jae; Park, Jong Seok; Jeong, Jin Oh; Jeong, Sung In; Gwon, Hui Jeong; Ahn, Sung Jun; Lim, Youn Mook

    2016-01-01

    Periodontitis is disease of damaged gum tissue that is not removed the plaque onto teeth. In case that the symptoms of disease get pain worse, it will have to extract tooth because of tumefy or bleeding at gums so treatment of drug was required to periodontitis. In this study, the hydrogel was prepared by including superior viscous, excellent elastic, and biocompatibility of Poly(vinyl alcohol, PVA) and antimicrobial drug of Metronidazole (MD). The 15 wt% PVA was dissolved in deionized water and then prepared PVA solution was irradiated using gamma-ray at 25 kGy (10 kGy hr"-"1). In addition, PVA hydrogel was immersed in each 0.1, 0.25 and 0.5 wt% MD solution using stirrer for 24 hr. The result of the gelation, 0.5 wt% MD loaded PVA hydrogel (76%) was lower than PVA hydrogel (88.2%). The swelling ration of 0.5 wt% MD loaded PVA hydrogel (294.8%) was higher than PVA hydrogel (105.2%). The compressive strength and thermal properties of MD loaded PVA hydrogel was gradually lower. The drug release test of 0.5 wt% MD loaded PVA hydrogel (61%) was higher than 0.1 wt% MD loaded PVA hydrogel (12%). Therefore, MD loaded PVA hygrogel may be a promising tool for periodontitis medicine by gamma-ray

  3. Combined Gemcitabine and Metronidazole Is a Promising Therapeutic Strategy for Cancer Stem-like Cholangiocarcinoma.

    Science.gov (United States)

    Kawamoto, Makoto; Umebayashi, Masayo; Tanaka, Hiroto; Koya, Norihiro; Nakagawa, Sinichiro; Kawabe, Ken; Onishi, Hideya; Nakamura, Masafumi; Morisaki, Takashi

    2018-05-01

    Metronidazole (MNZ) is a common antibiotic that exerts disulfiram-like effects when taken together with alcohol. However, the relationship between MNZ and aldehyde dehydrogenase (ALDH) activity remains unclear. This study investigated whether MNZ reduces cancer stemness by suppressing ALDH activity and accordingly reducing the malignancy of cholangiocarcinoma (CCA). We developed gemcitabine (GEM)-resistant TFK-1 cells and originally established CCA cell line from a patient with GEM-resistant CCA. Using these cell lines, we analyzed the impacts of MNZ for cancer stem cell markers, invasiveness, and chemosensitivity. MNZ reduced ALDH activity in GEM-resistant CCA cells, leading to decreased invasiveness and enhanced chemosensitivity. MNZ diminished the invasiveness by inducing mesenchymal-epithelial transition and enhancing chemosensitivity by increasing ENT1 (equilibrative nucleoside transporter 1) and reducing RRM1 (ribonucleotide reductase M1). MNZ reduced cancer stemness in GEM-resistant CCA cells. Combined GEM and MNZ would be a promising therapeutic strategy for cancer stem-like CAA. Copyright© 2018, International Institute of Anticancer Research (Dr. George J. Delinasios), All rights reserved.

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

    Directory of Open Access Journals (Sweden)

    George Tannous

    2010-09-01

    Full Text Available 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.

  5. Use and Effectiveness of Peri-Operative Cefotetan versus Cefazolin Plus Metronidazole for Prevention of Surgical Site Infection in Abdominal Surgery Patients.

    Science.gov (United States)

    Danan, Eleanor; Smith, Janessa; Kruer, Rachel M; Avdic, Edina; Lipsett, Pamela; Curless, Melanie S; Jarrell, Andrew S

    2018-04-24

    Current practice guidelines for antimicrobial prophylaxis in surgery recommend a cephamycin or cefazolin plus metronidazole for various abdominal surgeries. In February 2016, cephamycin drug shortages resulted in a change in The Johns Hopkins Hospital's (JHH) recommendation for peri-operative antibiotic prophylaxis in abdominal surgeries from cefotetan to cefazolin plus metronidazole. The primary objective of this study was to quantify the percentage of abdominal surgeries adherent to JHH peri-operative antibiotic prophylaxis guidelines. A sub-group analysis investigated whether prophylaxis with cefazolin plus metronidazole was associated with a lower rate of surgical site infections (SSIs) versus cefotetan. This retrospective cohort study included adult inpatients who underwent an abdominal surgery at JHH in September 2015 (Study Period I: cefotetan) or February to March 2016 (Study Period II: cefazolin plus metronidazole). Two hundred abdominal surgery cases were included in the primary analysis. A subset of 156 surgical cases were included in the sub-group analysis. The overall adherence rate to JHH guidelines was 75% in Study Period I versus 17% in Study Period II (p operative administration time (87% vs. 23%, p site infections occurred in 14% (12/83) of surgeries with cefotetan versus 8.2% (6/73) with cefazolin plus metronidazole for prophylaxis (p = 0.19). Adherence to an institution-specific peri-operative antibiotic prophylaxis guideline for abdominal surgeries was limited primarily by the longer infusion time required for pre-operative metronidazole. A higher percentage of SSIs occurred among abdominal surgeries with cefotetan versus cefazolin plus metronidazole for prophylaxis.

  6. Randomized clinical trial comparing the efficacy of the vaginal use of metronidazole with a Brazilian pepper tree (Schinus) extract for the treatment of bacterial vaginosis.

    Science.gov (United States)

    Leite, S R R F; Amorim, M M R; Sereno, P F B; Leite, T N F; Ferreira, J A C; Ximenes, R A A

    2011-03-01

    A 7.4% vaginal extract of the Brazilian pepper tree (Schinus terebinthifolius Raddi) was compared with 0.75% vaginal metronidazole, both manufactured by the Hebron Laboratory, for the treatment of bacterial vaginosis, used at bedtime for 7 nights. The condition was diagnosed using the combined criteria of Amsel and Nugent in two groups of 140 and 137 women, aged between 18 and 40 years. Intention-to-treat analysis was performed. Women were excluded from the study if they presented delayed menstruation, were pregnant, were using or had used any topical or systemic medication, presented any other vaginal infections, presented hymen integrity, or if they reported any history suggestive of acute pelvic inflammatory disease. According to Amsel's criteria separately, 29 patients (21.2%) treated with the extract and 87 (62.1%) treated with metronidazole were considered to be cured (P < 0.001). According to Nugent's score separately, 19 women (13.9%) treated with the extract and 79 (56.4%) treated with metronidazole were considered to be cured (P < 0.001). Using the two criteria together, the so-called total cure was observed in 17 women (12.4%) treated with the extract and in 79 women (56.4%) treated with metronidazole (P < 0.001). In conclusion, the cure rate for bacterial vaginosis using a vaginal gel from a pepper tree extract was lower than the rate obtained with metronidazole gel, while side effects were infrequent and non-severe in both groups.

  7. Effect of stearic acid on the properties of metronidazole/methocel K4M floating matrices

    Directory of Open Access Journals (Sweden)

    Belem Lara-Hernández

    2009-09-01

    Full Text Available The properties of metronidazole/Methocel K4M sustained release floating tablets have been studied varying the proportion of the lubricant, stearic acid, on formulations with and without sodium bicarbonate. The variables studied include technological properties of the tablets such as tablet hardness and ejection pressure, the drug release profile, the hydration kinetics and the floating behaviour. The presence of stearic acid and sodium bicarbonate improves the floating behaviour for more than 8 hours. The hydration volume, the tablet hardness and the ejection pressure decrease as the stearic acid content increases and the polymer content decreases. Drug dissolution increases with increasing proportions of stearic acid and decreasing proportions of the polymer in the tablets. The presence of sodium bicarbonate extends the differences in dissolution produced by stearic acid. These results are attributed to decreasing matrices coherence with an increasing quantity of stearic acid and a reducing polymer proportion. The carbon dioxide bubbles produced by sodium bicarbonate expand the matrices facilitating the dissolution, although their presence obstructs also the diffusion path through the hydrated gel layer.Estudaram-se as propriedades de comprimidos flutuantes de metronidazol/Methocel K4M de liberação controlada, variando-se a proporção do lubrificante, ácido esteárico, nas formulações com e sem bicarbonato de sódio. As variáveis estudadas incluem propriedades tecnológicas dos comprimidos, tais como dureza, pressão de ejeção, perfil de liberação do fármaco, cinética de hidratação e comportamento de flutuação. A presença de ácido esteárico e do bicarbonato de sódio melhora o comportamento de flutuação para mais de 8 horas. O volume de hidratação, a dureza e a pressão de ejeção do comprimido decrescem à medida que o conteúdo de ácido esteárico e de polímero diminui. A dissolução do fármaco aumenta com o

  8. Clostridium difficile Infection and Patient-Specific Antimicrobial Resistance Testing Reveals a High Metronidazole Resistance Rate.

    Science.gov (United States)

    Barkin, Jodie A; Sussman, Daniel A; Fifadara, Nimita; Barkin, Jamie S

    2017-04-01

    Clostridium difficile (CD) infection (CDI) causes marked morbidity and mortality, accounting for large healthcare expenditures annually. Current CDI treatment guidelines focus on clinical markers of patient severity to determine the preferred antibiotic regimen of metronidazole versus vancomycin. The antimicrobial resistance patterns for patients with CD are currently unknown. The aim of this study was to define the antimicrobial resistance patterns for CD. This study included all patients with stools sent for CD testing to a private laboratory (DRG Laboratory, Alpharetta, Georgia) in a 6-month period from across the USA. Patient data was de-identified, with only age, gender, and zip-code available per laboratory protocol. All samples underwent PCR testing followed by hybridization for CD toxin regions A and B. Only patients with CD-positive PCR were analyzed. Antimicrobial resistance testing using stool genomic DNA evaluated presence of imidazole- and vancomycin-resistant genes using multiplex PCR gene detection. Of 2743, 288 (10.5%) stool samples were positive for CD. Six were excluded per protocol. Of 282, 193 (69.4%) were women, and average age was 49.4 ± 18.7 years. Of 282, 62 were PCR positive for toxins A and B, 160 for toxin A positive alone, and 60 for toxin B positive alone. Antimicrobial resistance testing revealed 134/282 (47.5%) patients resistant to imidazole, 17 (6.1%) resistant to vancomycin, and 9 (3.2%) resistant to imidazole and vancomycin. CD-positive patients with presence of imidazole-resistant genes from stool DNA extract was a common phenomenon, while vancomycin resistance was uncommon. Similar to treatment of other infections, antimicrobial resistance testing should play a role in CDI clinical decision-making algorithms to enable more expedited and cost-effective delivery of patient care.

  9. Pharmacokinetics of metronidazole and its effect on the body during its use as a radiosensitizer

    International Nuclear Information System (INIS)

    Zel'vin, B.M.; Polyakov, P.Yu.; Zimina, E.S.; Dar'yalova, S.L.; Kiseleva, E.S.; Sokolova, I.I.

    1984-01-01

    During gamma-beam therapy (40-60 Gy) a study was made of the content of metronidazole (MZ) in the blood of 20 patients with oral mucosa cancer and 12 patients with esophageal cancer devending on a mode of its administration. A MZ effect on liver apd renal fUnction was studied. MZ was administered to the patients with cancer of both sites on the first 3 days of radiation therapy 3 h before an enlarged fraction of 4 Gy, estimated at 145 mg per 1 kg body mass (8-10 g) per os or via a gastrostoma and 15 h in rectal administration. In the patients with oral mucosa cancer after the administration of MZ per os its level which was sufficient for radiosensitization, was achieved after 2 h and remained for subsequent 4 h with maximum accumulation of 262-+22 μg/ml in the blood serum 3-4 h after administration. In the patients with esophageal cancer after MZ administration via the gastrostoma, the nature and time course of drug accumulation in the blood was identical, however accumulation maximum was lower and reached 219+-25 μg/ml. In the patients with esophageal cancer after MZ rectal administration, its level in the blood was 118 μg/ml only and did not achieve a therapeutically effective level. It is assumed that the lowering of MZ repeated dose by 20% will cause a decrease in the drug accumulation in the body and the degree of a toxic effect with maintaining its therapeutically effective level in the blood and tumor

  10. Amperometric Metronidazole Sensor Based on the Supermolecular Recognition by Metalloporphyrin Incorporated In Carbon Paste Electrode

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    Ru-Qin Yu

    2003-03-01

    Full Text Available An amperometric metronidazole (MTZ sensor using a glycosylated metalloporphyrin as a recognition element, which was incorporated in a carbon paste electrode, is reported. For the preparation of a MTZ-sensitive active material, 5, 10, 15, 20-tetrakis [2-(2, 3, 4, 6-tetraacetyl-β-D-glucopyranosyl-1-O-phenyl]porphyrin (T(oglu PPH2 and its Mn(III complex MnT(o-gluPPCl were synthesized from the reaction of pyrrole with ortho-acetylglycosylated benzaldehyde by Lindsay’s method. The MnT(oglu PPCl-modified electrode showed excellent selectivity toward MTZ with respect to a number of interferents and exhibited stable response. The calibration graph obtained with the proposed sensor was linear over the range of 2.9×10-3-5.8×10-8 M/L, with a detection limit of 5.8×10-8 M/L for MTZ. Cyclic voltammetric measurements indicated that MnT(oglu PPCl included in graphite-epoxy resin matrices could efficiently mediate electron transfer from the base electrode to MTZ causing a decrease of reduction potential for MTZ detection. The sensor could be regenerated by simply polishing with an alumina paper, with an excellent reproducibility (RSD=1.6%. The experimental conditions such as pH and applied working potential were optimized. The prepared sensor is applied for the determination of MTZ in pharmaceutical preparations and the results agreed with the values obtained by the pharmacopoeia method.

  11. Effect on the K/sub m/ for radiosensitization at 00C of thiol depletion by diethylmaleate pretreatment: quantitative differences found using the radiation sensitizing agent misonidazole or oxygen

    International Nuclear Information System (INIS)

    Koch, C.J.; Stobbe, C.C.; Bump, E.A.

    1984-01-01

    Pretreatment of V79-WNRE cells with 150 μM diethylmaleate for 1 hr at 37 0 C caused a decrease in intracellular glutathione levels to approximately 10-15% of control levels. The cells could be washed free of diethylmaleate and held at 0 0 C for several hours without toxicity and with no increase in glutathione concentration, although the glutathione concentration rapidly increased to normal levels at higher temperatures. Glutathione depletion itself caused a small but consistent radiosensitization of hypoxic cells (dose enhancement ratio of 1.2). However glutathione depletion caused a profound change in the radiosensitizing efficiency of misonidazole, with a decrease in K/sub m/ of about sevenfold from 0.6 to 0.09 mM. In contrast, only a 2.5-fold decrease was found in the K/sub m/ for radiosensitization by oxygen with diethylmaleate pretreatment. These results suggest a fundamental problem with the conventional theory of radiosensitivity whereby one considers a first-order competition for reaction with target radicals between radical-fixing versus radical-repairing species. It also suggests difficulties in the interpretation of glutathione as the only endogenous protective species

  12. Multivariate analysis of nystatin and metronidazole in a semi-solid matrix by means of diffuse reflectance NIR spectroscopy and PLS regression.

    Science.gov (United States)

    Baratieri, Sabrina C; Barbosa, Juliana M; Freitas, Matheus P; Martins, José A

    2006-01-23

    A multivariate method of analysis of nystatin and metronidazole in a semi-solid matrix, based on diffuse reflectance NIR measurements and partial least squares regression, is reported. The product, a vaginal cream used in the antifungal and antibacterial treatment, is usually, quantitatively analyzed through microbiological tests (nystatin) and HPLC technique (metronidazole), according to pharmacopeial procedures. However, near infrared spectroscopy has demonstrated to be a valuable tool for content determination, given the rapidity and scope of the method. In the present study, it was successfully applied in the prediction of nystatin (even in low concentrations, ca. 0.3-0.4%, w/w, which is around 100,000 IU/5g) and metronidazole contents, as demonstrated by some figures of merit, namely linearity, precision (mean and repeatability) and accuracy.

  13. Evaluation of the effects of albendazole and metronidazole on the ultrastructure of Giardia duodenalis, Trichomonas vaginalis and Spironucleus muris using transmission electron microscopy.

    Science.gov (United States)

    Oxberry, M E; Thompson, R C; Reynoldson, J A

    1994-08-01

    The three closely related parasitic protozoa, Giardia duodenalis, Trichomonas vaginalis and Spironucleus muris, all have very different sensitivities to albendazole and metronidazole. Ultrastructural studies reveal that the cytoskeletal elements of the ventral disk in G. duodenalis are affected by albendazole, whereas the other two parasites, neither of which possess this structure, are not affected by albendazole to the same extent. This suggests that albendazole may be having its primary affect on G. duodenalis by binding to cytoskeletal proteins and ultimately causing death of the parasite. Death may be occurring as the parasite loses its ability to adhere to the intestinal villi and obtain nutrients. Metronidazole showed a different pattern of activity against the three parasites. The evidence obtained from these ultrastructural studies supports the current theory that metronidazole adversely affects protozoa by disrupting inner cell membranes.

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

    Science.gov (United States)

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

    2016-12-01

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

  15. Efficacy and Safety of Metronidazole Monotherapy versus Vancomycin Monotherapy or Combination Therapy in Patients with Clostridium difficile Infection: A Systematic Review and Meta-Analysis.

    Directory of Open Access Journals (Sweden)

    Rui Li

    Full Text Available Clostridium difficile infection (CDI has become a global epidemiological problem for both hospitalized patients and outpatients. The most commonly used drugs to treat CDI are metronidazole and vancomycin. The aim of this study was to compare the efficacy and safety of metronidazole monotherapy with vancomycin monotherapy and combination therapy in CDI patients.A comprehensive search without publication status or other restrictions was conducted. Studies comparing metronidazole monotherapy with vancomycin monotherapy or combination therapy in patients with CDI were considered eligible. Meta-analysis was performed using the Mantel-Haenszel fixed-effects model, and odds ratios (ORs with 95% confidence intervals (95% CIs were calculated and reported.Of the 1910 records identified, seventeen studies from thirteen articles (n = 2501 patients were included. No statistically significant difference in the rate of clinical cure was found between metronidazole and vancomycin for mild CDI (OR = 0.67, 95% CI (0.45, 1.00, p = 0.05 or between either monotherapy and combination therapy for CDI (OR = 1.07, 95% CI (0.58, 1.96, p = 0.83; however, the rate of clinical cure was lower for metronidazole than for vancomycin for severe CDI (OR = 0.46, 95% CI (0.26, 0.80, p = 0.006. No statistically significant difference in the rate of CDI recurrence was found between metronidazole and vancomycin for mild CDI (OR = 0.99, 95% CI (0.40, 2.45, p = 0.98 or severe CDI (OR = 0.98, 95% CI (0.63, 1.53, p = 0.94 or between either monotherapy and combination therapy for CDI (OR = 0.91, 95% CI (0.66, 1.26, p = 0.56. In addition, there was no significant difference in the rate of adverse events (AEs between metronidazole and vancomycin (OR = 1.18, 95% CI (0.80, 1.74, p = 0.41. In contrast, the rate of AEs was significantly lower for either monotherapy than for combination therapy (OR = 0.30, 95% CI (0.17, 0.51, p < 0.0001.Metronidazole and vancomycin are equally effective for the

  16. Alterações inflamatórias provocadas pelo metronidazol em feridas: estudo experimental em ratos Inflammatory alterations provoked by metronidazole in wounds: an experimental study in rats

    Directory of Open Access Journals (Sweden)

    Cláudia Paraguaçu Pupo Sampaio

    2009-09-01

    Full Text Available CONTEXTO: Cerca de 2,7% da população brasileira tem úlceras crônicas nos pés e nas pernas, porcentagem que chega a 10% nos diabéticos e que representa a segunda causa de afastamento do trabalho no Brasil. Isso demonstra a necessidade de se encontrar um produto de baixo custo que favoreça a cicatrização dessas feridas. OBJETIVO: Avaliar os efeitos do metronidazol na cicatrização de feridas por segunda intenção. MÉTODOS: Utilizaram-se 80 ratos machos, em cujos dorsos se produziu uma ferida, distribuindo-se, os animais, em dois grupos de 40. Os ratos do grupo-controle tiveram suas feridas tratadas com solução de NaCl 0,9%, e os pertencentes ao grupo-experimento, com metronidazol 4%. No terceiro, sétimo, 14º e 21º dias, avaliou-se o processo cicatricial por parâmetros macroscópicos, histológicos e imunoistoquímicos. RESULTADOS: A concentração de colágeno foi maior nas cicatrizes dos animais do grupo-experimento em todos os tempos examinados. A concentração de colágeno do tipo I também foi significante no sétimo dia (p = 0,020 e no 21º dia (p = 0,016. O colágeno tipo III mostrou concentração semelhante nos tempos iniciais e apresentou-se com maior concentração no 21º dia (p = 0,005. A angiogênese, avaliada pelo anti-CD34, demonstrou maior número de vasos, no grupo-experimento, com diferença significante no terceiro dia (p CONTEXT: Chronic feet and leg ulcers affect about 2.7% of the Brazilian population, 10% of diabetic patients. The condition represents the second most frequent cause of absence from work in Brazil. This shows the need for a product that promotes healing of these wounds at a low cost. OBJECTIVE: To evaluate the effects of metronidazole on ulcer healing by second intention. METHODS: Eighty male rats divided into two groups of 40 had a wound made on their dorsum. The control group was treated with a 0.9% NaCl solution and the experimental group was treated with 4% metronidazole. On the third

  17. [Itraconazole and secnidazole capsules vs. vaginal ovules of fluocinolone acetonide, nystatin and metronidazole in the symptomatic treatment of vaginitis].

    Science.gov (United States)

    Alvarado García, A; Gaviño Ambriz, S

    1998-04-01

    Evaluation of oral treatment in vaginitis and vaginosis using Itraconazol and sechidazol, in comparison to topic treatment using vaginal ovules of acetonido of fluocinolona 0.50 mg, nistatina 100,000 U and metronidazol 500 mg. Longitudinal, prospective and open comparative study. Servicio de Reproducción Humana(Human Reproduction Department), Centro Médico Nacional "20 de Noviembre". Forty female patients, without any relevant differences in their general characteristics, chose diagnosis was vaginitis and vaginosis, who were medically treated through external consultation, divided in two groups of twenty each one. Group 1 oral treatment with itraconazol and secnidazol. Group 2 had topic treatment with fluocinolona, nistatina and metronidazol. All of the patients were controlled in seven and fourteen days time, in order to evaluate the intensity of their clinical symptomatology, as well as the efficacy in both ways of treatment. Leukorrhea was the most important symptom in all the cases, going from minor to serious white discharge. After the treatment, we found a relevant difference statistically significative in patients treated with intraconazol and secnidazol. We did not find any differences in relation to ardor, pruritus, dispareunia and disuria at post-treatment evaluation. However, group 1 betterment was statistically significative between the first and the seventh days of treatment. Treating vaginitis or vaginosis (or both) with itraconazol and secnidazol takes less time for betterment in addition to comfort and easiness of oral administration; therefore, we consider them proper medicines in these specific cases.

  18. Determination of metronidazole in a rat stomach by HPLC for obtaining basic data of the eradication therapy of Helicobacter pylori

    Directory of Open Access Journals (Sweden)

    Mai Kubodera

    2012-10-01

    Full Text Available In the eradication therapy of Helicobacter pylori changes of antibiotics as these concentrations or amount in the stomach after oral administration were not clear. A simple and accurate method for determining the concentration of metronidazole (MTZ in homogenate of rat stomach was developed in order to obtain basic data to design a pharmaceutical preparation having targeting ability to the surface of gastric-mucosa. This method included a deproteinization process by methanol, separation with reversed-phase high-performance liquid chromatography, and detection with an ultraviolet wavelength of 370 nm. Regression analysis showed that the method was linear over a standard curve range from 5 μg/mL to 2000 μg/mL. The inter-day precision and accuracy values between the ranges were 5.0% or better and −7.5 to 5.2%, respectively. The newly developed method was applied to an analysis of gastric samples after oral administration of MTZ at a dose of 5 mg/kg. It was found that the residual MTZ in the stomach was determined within 5 h after dosing. This method is useful for monitoring MTZ in stomach after its oral administration to rats. Keywords: Metronidazole, HPLC, Homogenate, Stomach, Rat

  19. Pharmaceutical evaluation and comparison of different brands of metronidazole available in the local market of Peshawar (Pakistan

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    Muhammad Adil

    2016-08-01

    Full Text Available Objective: To assess the pharmaceutical quality of different brands of metronidazole manufactured, available and prescribed by the doctors of Peshawar, Pakistan. Methods: Different film-coated metronidazole products manufactured by multinational and national pharmaceutical industries and prescribed by the doctors were collected from Peshawar, Khyber Pakhtunkhwa, Pakistan. Their hysico-chemical properties were assessed, which included friability, hardness, disintegration, dissolution and weight variation tests according to the the United States Pharmacopoeia (USP standards. Results: All the brands showed a average weight of 5.74 g for 13 tablets (products A–M. Product J had the highest weight and products D and E failed the hardness, friability and disintegration time according to USP standards. Products M, K and G, L failed disintegration test and dissolution test, respectively. Weight variation of all the products proved statistically that they were in accordance with the standards of USP. Conclusions: The study suggested that products A, F, H and J passed all the tests according to the USP standards while the rest of them did not fulfill the standards specification.

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

    Directory of Open Access Journals (Sweden)

    Flore Dossou-Yovo

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

  1. Response of the RIF-1 tumor in vitro and in C3H/Km mice to x-radiation (cell survival, regrowth delay, and tumor control), chemotherapeutic agents, and activated macrophages

    International Nuclear Information System (INIS)

    Brown, J.M.; Twentyman, P.R.; Zamvil, S.S.

    1980-01-01

    The radiation response of logarithmic growth phase and fed plateau phase RIF-1 cells in vitro was found to be characterized by D 0 values of 110 and 133 rads and extrapolation numbs of 36 and 28, respectively. The response of the tumor in vivo to X-irradiation in nonanesthetized mice showed a dependence on the tumor implantation site. In the leg muscle, the response indicated that most cells were at an intermediate level of oxygenation, whereas in the subcutaneous tissue of the flank, the response of the tumor indicated that it had a small fraction of hypoxic cells of maximum radioresistance. Misonidazole radiosensitized the leg-implanted tumor as measured both by cell survival and regrowth delay. The tumor was relatively insensitive to a single dose of 1,3-bis(2-chloroethyl)-1-nitrosourea, sensitive to a single dose of cis-platinum, and highly sensitive to a single dose of cyclophosphamide

  2. Toxic and radiosensitizina effect of reduced nitroimidazoles on E.COLI B/r cells

    International Nuclear Information System (INIS)

    Ryabchenko, N.I.; Semin, Yu.A.; Petrova, K.M.; Kutmin, A.I.

    1983-01-01

    The spectrophotometric method was used to study the rate of chemical reduction of misonidazole and metronidazole by NH 4 Cl and Zn in the atmosphere of argon and oxygen. Reduction of drugs increased their toxicity for hypoxic and oxygenated E. coli B/r. The reduced metronidazole is a more effective radiosensitizer of hypoxic E. coli B/r than the original compound

  3. A comparative study of precision cut liver slices, hepatocytes, and liver microsomes from the Wistar rat using metronidazole as a model substance

    DEFF Research Database (Denmark)

    Sidelmann, U. G.; Cornett, Claus; Tjornelund, J.

    1996-01-01

    1. Metronidazole is metabolized by rat liver in vitro models to form a hydroxy metabolite, an acetic acid metabolite, a glucuronic acid conjugate, and a sulphate conjugate. 2. Four different in vitro systems for investigation of drug metabolism based on liver preparations from the male Wistar rat...

  4. First report of metronidazole resistant, nimD-positive, Bacteroides stercoris isolated from an abdominal abscess in a 70-year-old woman

    DEFF Research Database (Denmark)

    Otte, Erik; Nielsen, Hans Linde; Hasman, Henrik

    2017-01-01

    We here present the first case of a metronidazole resistant nimD positive Bacteroides stercoris. The isolate originated from a polymicrobial intra-abdominal abscess in a 70-year-old woman. The nimD gene was detected by use of whole-genome shotgun sequencing and the subsequent use of the ResFinder 2...

  5. Efficacy of 1% terbinafine cream in comparison with 0.75% metronidazole gel for the treatment of papulopustular rosacea.

    Science.gov (United States)

    Serdar, Zehra Aşiran; Yaşar, Şirin

    2011-06-01

    Topical antifungals comprising imidazole derivatives have been used for the treatment of rosacea previously, owing to their anti-inflammatory activities. Terbinafine, an antifungal agent belongs to allylamine group, has also anti-inflammatory effects. Currently, there are only a few unpublished studies, in which terbinafine has been used systemically for rosacea treatment. In this single-blind, 8-week study, we investigated the potential efficacy and safety of terbinafine 1% cream for the treatment of mild and moderate papulopustular rosacea, and compared the results with those of 0.75% metronidazole gel. Forty patients, 30 females and 10 males, with papulopustular rosacea were enrolled into the study between 2006 and 2007 years. Twenty of the patients were instructed to apply 1% terbinafine cream, whereas others patients of the study population were instructed to use 0.75% metronidazole gel. A total of 32 patients completed the study. Pre-treatment and post-treatment total severity score (TSS) of the disease were determined by assessing the severity of erythema/telangiectasia, and the number of papules/pustules of the whole face. The overall response rates, differences of pre-/post-treatment scores of each criterium and the percentages of the decrease in TSS of the study groups were compared statistically. There was no statistically significant difference between the groups in terms of age, sex, and disease duration (P = 0.937, 1.000, and 0.055, respectively). No significant difference was found between the mean post-treatment TSSs of the two groups (P = 0.605). The percentage of clearance assessed by the differences between pre-treatment and post-treatment TSSs was 55% in terbinafine group, although the percentage was 45% in metronidazole group, with no statistically significant difference between the groups (P = 0.496). Local side effects including erythema, pruritus, and burning were mild and transient in both groups, with similar frequencies (P = 0.101). This

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

    Science.gov (United States)

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

    2016-02-05

    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. Copyright © 2015 Elsevier B.V. All rights reserved.

  7. [Comparative study of combined local treatment (sulfadimidine, metronidazole and nystatin) and the standard monotherapy in uncomplicated bacterial vaginosis].

    Science.gov (United States)

    Milánkovits, Márton; Baksay, László; Plachy, János

    2002-12-22

    Comparative, in vivo, human, prospective, single blind, clinical and microbiological diagnoses based and randomised study of the treatment of uncomplicated bacterial vaginosis with two forms of combined (metronidazole + nystatin + sulfadimidin) vaginal suppositories (laminated and mixed containing the same ingredients) and the standard preparations available in the Hungarian market (Dalacin vaginal cream and Klion vaginal suppository). The examinations involved 60 volunteers and were performed in the Gynecological Outpatient Clinic of the Council of Erd, the microbiological samples were examined at Saint Rókus Hospital in Budapest. The combined treatment was better tolerated and resulted in normal vaginal pH significantly more often at the same rate of recovery. The combined treatment is simultaneously effective in cases of the most prevalent coinfections too.

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

    Science.gov (United States)

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

    2015-05-15

    This paper discusses a general method for the use of orthogonal polynomials for unequal intervals (OPUI) to eliminate interferences in two-component spectrophotometric analysis. In this paper, a new approach was developed by using first derivative D1 curve instead of absorbance curve to be convoluted using OPUI method for the determination of metronidazole (MTR) and nystatin (NYS) in their mixture. After applying derivative treatment of the absorption data many maxima and minima points appeared giving characteristic shape for each drug allowing the selection of different number of points for the OPUI method for each drug. This allows the specific and selective determination of each drug in presence of the other and in presence of any matrix interference. The method is particularly useful when the two absorption spectra have considerable overlap. The results obtained are encouraging and suggest that the method can be widely applied to similar problems. Copyright © 2015 Elsevier B.V. All rights reserved.

  9. Differential benefits of amoxicillin-metronidazole in different phases of periodontal therapy in a randomized controlled crossover clinical trial.

    Science.gov (United States)

    Mombelli, Andrea; Almaghlouth, Adnan; Cionca, Norbert; Courvoisier, Delphine S; Giannopoulou, Catherine

    2015-03-01

    The specific advantage of administering systemic antibiotics during initial, non-surgical therapy or in the context of periodontal surgery is unclear. This study assesses the differential outcomes of periodontal therapy supplemented with amoxicillin-metronidazole during either the non-surgical or the surgical treatment phase. This is a single-center, randomized placebo-controlled crossover clinical trial with a 1-year follow-up. Eighty participants with Aggregatibacter actinomycetemcomitans-associated moderate to advanced periodontitis were randomized into two treatment groups: group A, antibiotics (500 mg metronidazole plus 375 mg amoxicillin three times per day for 7 days) during the first, non-surgical phase of periodontal therapy (T1) and placebo during the second, surgical phase (T2); and group B, placebo during T1 and antibiotics during T2. The number of sites with probing depth (PD) >4 mm and bleeding on probing (BOP) per patient was the primary outcome. A total of 11,212 sites were clinically monitored on 1,870 teeth. T1 with antibiotics decreased the number of sites with PD >4 mm and BOP per patient significantly more than without (group A: from 34.5 to 5.7, 84%; group B: from 28.7 to 8.7, 70%; P antibiotics, but only eight treated with placebo, achieved a 10-fold reduction of diseased sites (P = 0.007). Consequently, fewer patients of group A needed additional therapy, the mean number of surgical interventions was lower, and treatment time in T2 was shorter. Six months after T2, the mean number of residual pockets (group A: 2.8 ± 5.2; group B: 2.2 ± 5.0) was not significantly different and was sustained over 12 months in both groups. Giving the antibiotics during T1 or T2 yielded similar long-term outcomes, but antibiotics in T1 resolved the disease quicker and thus reduced the need for additional surgical intervention.

  10. Controlled release of metronidazole from composite poly-ε-caprolactone/alginate (PCL/alginate) rings for dental implants.

    Science.gov (United States)

    Lan, Shih-Feng; Kehinde, Timilehin; Zhang, Xiangming; Khajotia, Sharukh; Schmidtke, David W; Starly, Binil

    2013-06-01

    Dental implants provide support for dental crowns and bridges by serving as abutments for the replacement of missing teeth. To prevent bacterial accumulation and growth at the site of implantation, solutions such as systemic antibiotics and localized delivery of bactericidal agents are often employed. The objective of this study was to demonstrate a novel method of controlled localized delivery of antibacterial agents to an implant site using a biodegradable custom fabricated ring. The study involved incorporating a model antibacterial agent (metronidazole) into custom designed poly-ε-caprolactone/alginate (PCL/alginate) composite rings to produce the intended controlled release profile. The rings can be designed to fit around the body of any root form dental implants of various diameters, shapes and sizes. In vitro release studies indicate that pure (100%) alginate rings exhibited an expected burst release of metronidazole in the first few hours, whereas Alginate/PCL composite rings produced a medium burst release followed by a sustained release for a period greater than 4 weeks. By varying the PCL/alginate weight ratios, we have shown that we can control the amount of antibacterial agents released to provide the minimal inhibitory concentration (MIC) needed for adequate protection. The fabricated composite rings have achieved a 50% antibacterial agent release profile over the first 48 h and the remaining amount slowly released over the remainder of the study period. The PCL/alginate agent release characteristic fits the Ritger-Peppas model indicating a diffusion-based mechanism during the 30-day study period. The developed system demonstrates a controllable drug release profile and the potential for the ring to inhibit bacterial biofilm growth for the prevention of diseases such as peri-implantitis resulting from bacterial infection at the implant site. Copyright © 2013 Academy of Dental Materials. Published by Elsevier Ltd. All rights reserved.

  11. Collateral Effects of Antibiotics: Carbadox and Metronidazole Induce VSH-1 and Facilitate Gene Transfer among Brachyspira hyodysenteriae Strains▿

    Science.gov (United States)

    Stanton, Thaddeus B.; Humphrey, Samuel B.; Sharma, Vijay K.; Zuerner, Richard L.

    2008-01-01

    Brachyspira hyodysenteriae is an anaerobic spirochete and the etiologic agent of swine dysentery. The genome of this spirochete contains a mitomycin C-inducible, prophage-like gene transfer agent designated VSH-1. VSH-1 particles package random 7.5-kb fragments of the B. hyodysenteriae genome and transfer genes between B. hyodysenteriae cells. The chemicals and conditions inducing VSH-1 production are largely unknown. Antibiotics used in swine management and stressors inducing traditional prophages might induce VSH-1 and thereby stimulate lateral gene transfer between B. hyodysenteriae cells. In these studies, VSH-1 induction was initially detected by a quantitative real-time reverse transcriptase PCR assay evaluating increased transcription of hvp38 (VSH-1 head protein gene). VSH-1 induction was confirmed by detecting VSH-1-associated 7.5-kb DNA and VSH-1 particles in B. hyodysenteriae cultures. Nine antibiotics (chlortetracycline, lincomycin, tylosin, tiamulin, virginiamycin, ampicillin, ceftriaxone, vancomycin, and florfenicol) at concentrations affecting B. hyodysenteriae growth did not induce VSH-1 production. By contrast, VSH-1 was detected in B. hyodysenteriae cultures treated with mitomycin C (10 μg/ml), carbadox (0.5 μg/ml), metronidazole (0.5 μg/ml), and H2O2 (300 μM). Carbadox- and metronidazole-induced VSH-1 particles transmitted tylosin and chloramphenicol resistance determinants between B. hyodysenteriae strains. The results of these studies suggest that certain antibiotics may induce the production of prophage or prophage-like elements by intestinal bacteria and thereby impact intestinal microbial ecology. PMID:18359835

  12. Intensification of antitumor radiation effect by metronidazole and short-term hyperglycemia and dependence of therapeutic effect on schedules of fractionation and value of single dose

    International Nuclear Information System (INIS)

    Venkhvadze, N.G.

    1988-01-01

    Combined application of metronidazole and short-term hyperglycemia under fractionated irradiation of sarcoma-45, 340 in white rats-males is studied. Tumors were γ-irradiated with 60 Co threefold in 48 hours at 15 Gy single dose or irradiated threefold in a week at 20, 25 and 30 Gy doses. Efficiency of experimental therapy is cheked by dynamics of tumor regression, a number of animals with tumors reabsorbed temporarily, a number of animals recovered and time of tumor grouth up to the initial volume. It is established that combined application of metronidazole and short-term hyperglycemia under fractionated irradiation increases essentially the efficiency of radiotherapy carried out by large fractions with great time intervals. 7 refs.; 1 fig.; 2 tabs

  13. Long-term results of treatment of patients with metronidazole and protracted radiotherapy: a base for comparative randomized studies with hypoxic radiosensitizers

    International Nuclear Information System (INIS)

    Karim, A.B.M.F.; Njo, K.H.

    1982-01-01

    From 1974 to 1978, a pilot study was undertaken in the Academic Hospital of the Free University of Amsterdam to evaluate the use of hypoxic radiosensitizer metronidazole given with conventional protracted radiotherapy. All patients had advanced malignancies, 70 head and neck cancers being available for long-term evaluation. Only four showed evidence of (reversible) neuropathy, including one patient with two attacks of reversible psychosis. With a minimum follow-up period of 30 months, the local control rates of some of these tumors appear to be encouraging and higher (54%) than usually obtained, without evidence of any long-term enhanced late effect of radiation or carcinogenesis. Clinical benefit has been persistently reported from metronidazole from a number of centers. Reports on other hypoxic radiosensitizers are not always clearly encouraging to date. In view of these facts, three-armed studies appear desirable and are being pursued

  14. Are there specific benefits of amoxicillin plus metronidazole in Aggregatibacter actinomycetemcomitans-associated periodontitis? Double-masked, randomized clinical trial of efficacy and safety.

    Science.gov (United States)

    Mombelli, Andrea; Cionca, Norbert; Almaghlouth, Adnan; Décaillet, Fabien; Courvoisier, Delphine S; Giannopoulou, Catherine

    2013-06-01

    It has been suggested that prescription of amoxicillin plus metronidazole in the context of periodontal therapy should be limited to patients with specific microbiologic profiles, especially those testing positive for Aggregatibacter actinomycetemcomitans. The main purpose of this analysis is to determine if patients positive for A. actinomycetemcomitans with moderate to advanced periodontitis benefit specifically from amoxicillin plus metronidazole given as an adjunct to full-mouth scaling and root planing. This is a double-masked, placebo-controlled, randomized longitudinal study including 41 participants who were positive for A. actinomycetemcomitans and 41 participants who were negative for A. actinomycetemcomitans. All 82 patients received full-mouth periodontal debridement performed within 48 hours. Patients then received either systemic antibiotics (375 mg amoxicillin and 500 mg metronidazole, three times daily) or placebo for 7 days. The primary outcome variable was persistence of sites with a probing depth (PD) >4 mm and bleeding on probing (BOP) at the 3-month reevaluation. Using multilevel logistic regression, the effect of the antibiotics was analyzed according to the following factors (interaction effect): A. actinomycetemcomitans-positive or -negative at baseline, sex, age, smoking, tooth being a molar, and interdental location. At reevaluation, participants in the test group had significantly fewer sites with a persisting PD >4 mm and BOP than control patients (P antibiotics. Patients benefited from the antibiotics irrespective of sex, age, or smoking status. Molars benefited significantly more from the antibiotics than non-molars (P for interaction effect = 0.03). Patients who were positive for A. actinomycetemcomitans had no specific benefit from amoxicillin plus metronidazole. Sites on molars benefited significantly more from the antibiotics than non-molar sites.

  15. [Pharmacokinetics/pharmacodinamic (PK/PD) evaluation of a short course of oral administration of metronidazole for the management of infections caused by Bacteroides fragilis].

    Science.gov (United States)

    Morales-León, Felipe; von Plessing-Rossel, Carlos; Villa-Zapata, Lorenzo; Fernández-Rocca, Pola; Sanhueza-Sanhueza, Cindy; Bello-Toledo, Helia; Mella-Montecinos, Sergio

    2015-04-01

    Metronidazole is the antibiotic of choice for the management of infections caused by anaerobes. Its administration requires multiple daily doses causing increased medication errors. Due to its high post-antibiotic effect and rapid concentration-dependent bactericidal activity, administration of this antibiotic in an extended dosing interval would achieve PK/PD parameters effectively. To assess the probability of achieving effective PK/PD relationship with the administration of 1,000 mg every 24 hours of metronidazole for Bacteroides fragilis infections. A clinical trial was conducted in a group of volunteers who received a single oral dose of 500 or 1,000 mg of metronidazole. Determinations of values of Cmax, t max, and AUCC0-24 h. determined using the trapezoidal method, were obtained for a Markov simulation that would allow for determining the likelihood of achieving a AUC0-24 h/MIC ratio above 70 for infections caused by susceptible B. fragilis. Cmax (24,03 ± 6,89 mg/L) and t max (1,20 ± 0.80 hrs) and the value of AUC0-24 h (241.91 ± 48.14 mg * h/L) were determined. The probability of obtaining a AUC0-24 h/MIC ratio greater than 70 was greater than 99%. From a pharmacokinetic perspective, with the administration of a daily dose of 1,000 mg of metronidazole, it is possible to achieve a therapeutic goal of AUC0-24 h/MIC ratio above 70 for the treatment of anaerobic infections.

  16. Simultaneous detection of metronidazole and chloramphenicol by differential pulse stripping voltammetry using a silver nanoparticles/sulfonate functionalized graphene modified glassy carbon electrode

    International Nuclear Information System (INIS)

    Zhai, Haiyun; Liang, Zhixian; Chen, Zuanguang; Wang, Haihang; Liu, Zhenping; Su, Zihao; Zhou, Qing

    2015-01-01

    Graphical abstract: Display Omitted -- Highlights: • A novel and reliable AgNPs/SF-GR modified glassy carbon electrode was constructed and characterized. • The AgNPs/SF-GR/GCE was successfully applied in the shrimp for simultaneous determination of MTZ and CAP. • Under optimized conditions, common substances such as UA, AA, DA and ion did not interfered in the electrode performance. • The modified electrode exhibited considerable sensitivity, stability and reproducibility. • This fabricated electrode achieved a satisfactory level compared with other electrodes toward MTZ and CAP. -- Abstract: A novel silver nanoparticles/sulfonated functionalized graphene modified glassy carbon electrode (AgNPs/SF-GR/GCE) was fabricated to determine chloramphenicol and metronidazole simultaneously. Taking advantage of sulfonic group, AgNPs were successfully electrodeposited on functionalized GR immobilized on the surface of a GCE. Scanning electron microscopy and energy spectrum analysis results confirmed that AgNPs were deposited on the functionalized GR film. Compared to the bare GCE or the pristine SF-GR modified electrode, AgNPs/SF-GR/GCE exhibited excellent electroreduction towards chloramphenicol and metronidazole. In addition, the two antibacterial drugs were separated completely in 0.10 M citric acid-sodium citrate buffer (pH 4.0) by differential pulse stripping voltammetry under optimum conditions. The cathodic current was linearly related with 0.02∼20.0 μM chloramphenicol and 0.10∼20.0 μM metronidazole, with the detection limits of 0.01 μM and 0.05 μM respectively. Furthermore, AgNPs/SF-GR/GCE was applied to the simultaneous determination of chloramphenicol and metronidazole in an aquatic product

  17. Addition of Ceftriaxone and Amikacin to a Ciprofloxacin plus Metronidazole Regimen for Preventing Infectious Complications of Transrectal Ultrasound-Guided Prostate Biopsy: A Randomized Controlled Trial

    Directory of Open Access Journals (Sweden)

    Mohammad-Hossein Izadpanahi

    2017-01-01

    Full Text Available Background. The objective of this study was to evaluate the efficacy of adding single doses of ceftriaxone and amikacin to a ciprofloxacin plus metronidazole regimen on the reduction of infectious complications following transrectal ultrasound-guided prostate biopsy (TRUS Bx. Materials and Methods. Four hundred and fifty patients who were candidates for TRUS Bx were divided into two groups of 225 each. The control group received ciprofloxacin 500 mg orally every 12 hours together with metronidazole 500 mg orally every 8 hours from the day prior to the procedure until the fifth postoperative day. In the second group, single doses of ceftriaxone 1 g by intravenous infusion and amikacin 5 mg/kg intramuscularly were administered 30–60 minutes before TRUS Bx in addition to the oral antimicrobials described for group 1. The incidence of infection was compared between the groups. Results. The incidence of infectious complications in the intervention group was significantly lower than that in the control group (4.6% versus 0.9%, p=0.017. Conclusion. The addition of single doses of intramuscular amikacin and intravenously infused ceftriaxone to our prophylactic regimen of ciprofloxacin plus metronidazole resulted in a statistically significant reduction of infectious complications following TRUS Bx.

  18. Preliminary investigation of the possibility for implementation of modified pharmacopoeial HPLC methods for quality control of metronidazole and ciprofloxacin in medicinal products used in veterinary medicine

    Directory of Open Access Journals (Sweden)

    Marjan Piponski

    2015-03-01

    Full Text Available Quality control of veterinary medicine products containing two different frequently used antibiotics metronidazole and ciprofloxacin hydrochloride, was considered and performed, using modified pharmacopoeial HPLC methods. Three different HPLC systems were used: Varian ProStar, Perkin Elmer Series and UPLC Shimadzu Prominence XR. The chromatographic columns used were LiChropher RP Select B 75 mm x 4 mm with 5 μm particles and Discovery C18 100 mm x 4,6 mm with 5 μm particles. Chromatographic methods used for both analytes were compendial, with minor modifications made for experimental purposes. Minor modifications of the pharmacopoeia prescribed chromatographic conditions, in both cases, led to better chromatographic parameters, good resolution and shorter analysis times. Optimized methods can be used for: determination of metronidazole in gel formulation, for its simultaneous quantification with preservatives present in the formulation and even for identification and quantification of its specified impurity, 2-methyl-5-nitroimidazole; determination of ciprofloxacin hydrochloride in film coated tablets and eye drops and identification and quantification of its specified impurities. These slightly modified and optimized pharmacopoeial methods for quality control of metronidazole and ciprofloxacin dosage forms used in veterinary medicine can be successfully applied in laboratories for quality control of veterinary medicines.

  19. Post-irradiation degradation of DNA in electron and neutron-irradiated E. coli B/r; the effect of the radiation sensitizer metronidazole

    Energy Technology Data Exchange (ETDEWEB)

    Cramp, W A; George, A M; Howlett, J [Hammersmith Hospital, London (UK). M.R.C. Cyclotron Unit

    1976-04-01

    Suspensions of E.coli B/r were irradiated under aerobic and anoxic conditions with electrons (7 to 8 MeV, 2 and 20 krad/min, MRC linear accelerator), or with neutrons (average energy 7.5 MeV, 2 krad/min, MRC cyclotron) in an investigation of the effects of the radiosensitizer, metronidazole (Flagyl, 5 or 10 mM) on survival and DNA degradation. These results are compared with those for another electron affinic radiosensitizer, indane trione. Survival studies yielded enhancement ratios, for anoxic irradiation only, of 1.7 (5mM) and 1.9 (10mM) for electrons, and 1.2 (5mM and 10mM) for neutrons. Unlike indane trione, metronidazole had no pronounced inhibitory effect on post-irradiation DNA degradation, either when incubated with the bacteria before irradiation or when present during irradiation. When present under anoxic conditions of irradiation with electrons, some enhancement of degradation was observed. DNA degradation was reduced at higher doses, with a pronounced maxiumum effect, for neutrons as well as for electrons. Metronidazole allowed this degradation to continue and showed some sensitizing action, but did not prevent the decrease in total degradation at high doses. It is therefore difficult to correlate DNA degradation with cell-depth.

  20. Evaluation of 2-amino-5-nitrothiazole as a hypoxic cell radiosensitizer

    International Nuclear Information System (INIS)

    Rockwell, S.; Mroczkowski, Z.; Rupp, W.D.

    1982-01-01

    The nitroheterocyclic compound 2-amino-5-nitrothiazole (ANT) was evaluated as a hypoxic radiosensitizer. Experiments with bacteria showed that this agent was similar to misonidozole in radiosensitizing activity, but was less cytotoxic and less mutagenic than misonidazole. Experiments with EMT6 tumor cells in culture showed ANT to be an effective hypoxic radiosensitizer, although slightly less active than misonidazole, and to be less cytotoxic than misonidazole. ANT was more toxic to mice than misonidazole and produced a spectrum of symptoms, including hyperactivity and agitation, different from those of misonidazole. The toxicities of ANT and misonidazole were additive. The maximum levels of ANT achieveable in the tumors after ip injection of nontoxic doses of drug were low ( -4 M) and the radiosensitization obtainable with the drug in vivo was inferior to that obtainable with misonidazole. These findings suggest that nitrothiazoles might be an interesting class of nitroheterocyclic radiosensitizers, but that molecules with increased solubility and improved pharmacokinetics would be necessary for efficacy in vivo

  1. Effect of antimicrobial therapy on the gastrointestinal bacterial flora, infection and mortality in mice exposed to different doses of irradiation

    Energy Technology Data Exchange (ETDEWEB)

    Brook, I.; Ledney, G.D. (Armed Forces Radiobiology Research Inst., Bethesda, MD (United States))

    1994-01-01

    The effect of antimicrobial therapy on gut flora, sepsis, and mortality was investigated in C[sub 3]H/HeN female mice irradiated with 7.0, 8.0 or 8.5 Gy or [sup 60]Co. The antimicrobial agents tested were metronidazole, penicillin, imipenem, gentamicin and ofloxacin. In control mice, the greatest reduction of lactose fermenting organisms (1.7-2.8 logs) occurred on day 8 after irradiation and were related directly to radiation doses. After day 8 lactose fermenting organism levels increased and the increases were associated with mortality due to Enterobacteriaceae sepsis. Irradiation reduced the populations of strict anaerobic bacteria in control mice by 2-8 logs, and these remained at low levels. Treatment with either metronidazole or penicillin resulted in greater reductions of strict anaerobic bacteria than occurred in the controls and induced earlier and greater increases in lactose fermenting organisms and associated mortality. Therapies with either gentamicin or ofloxacin resulted in lesser reductions of strict anaerobic bacteria (1.1-2.2 logs) than occurred in controls, and caused greater decreases in lactose fermenting organisms and mortality. The changes in the bacterial flora and mortality following imipenem treatment were similar to controls. These data demonstrate that in animals exposed to irradiation, antimicrobial agents effective against strict anaerobic bacteria can be deleterious, but antimicrobial agents effective against lactose fermenting organsims may be beneficial. (Author).

  2. Effect of antimicrobial therapy on the gastrointestinal bacterial flora, infection and mortality in mice exposed to different doses of irradiation

    International Nuclear Information System (INIS)

    Brook, I.; Ledney, G.D.

    1994-01-01

    The effect of antimicrobial therapy on gut flora, sepsis, and mortality was investigated in C 3 H/HeN female mice irradiated with 7.0, 8.0 or 8.5 Gy or 60 Co. The antimicrobial agents tested were metronidazole, penicillin, imipenem, gentamicin and ofloxacin. In control mice, the greatest reduction of lactose fermenting organisms (1.7-2.8 logs) occurred on day 8 after irradiation and were related directly to radiation doses. After day 8 lactose fermenting organism levels increased and the increases were associated with mortality due to Enterobacteriaceae sepsis. Irradiation reduced the populations of strict anaerobic bacteria in control mice by 2-8 logs, and these remained at low levels. Treatment with either metronidazole or penicillin resulted in greater reductions of strict anaerobic bacteria than occurred in the controls and induced earlier and greater increases in lactose fermenting organisms and associated mortality. Therapies with either gentamicin or ofloxacin resulted in lesser reductions of strict anaerobic bacteria (1.1-2.2 logs) than occurred in controls, and caused greater decreases in lactose fermenting organisms and mortality. The changes in the bacterial flora and mortality following imipenem treatment were similar to controls. These data demonstrate that in animals exposed to irradiation, antimicrobial agents effective against strict anaerobic bacteria can be deleterious, but antimicrobial agents effective against lactose fermenting organsims may be beneficial. (Author)

  3. Solar photoelectro-Fenton degradation of the antibiotic metronidazole using a flow plant with a Pt/air-diffusion cell and a CPC photoreactor

    International Nuclear Information System (INIS)

    Pérez, Tzayam; Garcia-Segura, Sergi; El-Ghenymy, Abdellatif; Nava, José L.; Brillas, Enric

    2015-01-01

    Highlights: • Degradation of metronidazole solutions at pH 3.0 by EF and SPEF in a flow plant. • High recalcitrance of the antibiotic and its products to be destroyed by ·OH radicals. • Only 53% mineralization by the most potent SPEF process at 55.4 mA cm −2 . • 5 heterocyclic products, 12 hydroxylated derivatives and 2 carboxylic acids were found. • Release of NO 3 − ion and generation of persistent N-products and N-volatile species. - Abstract: The degradation of 10 dm 3 of solutions of the heterocyclic antibiotic metronidazole in 0.10 mol dm −3 Na 2 SO 4 of pH 3.0 has been comparatively studied by electro-Fenton (EF) and solar photoelectro-Fenton (SPEF). Experiments were performed in a solar flow plant equipped with a Pt/air-diffusion cell and coupled to a compound parabolic collector (CPC) photoreactor. A very weak mineralization was found for the EF process in the dark, indicating a large recalcitrance of heterocyclic compounds to be destroyed by hydroxyl radicals formed at the Pt anode from water oxidation and mainly in the bulk from Fenton's reaction between added Fe 2+ and cathodically generated H 2 O 2 . The quick photolysis of intermediates by UV radiation from sunlight enhanced largely the mineralization process by SPEF. The effect of applied current density and Fe 2+ and drug contents on the SPEF treatment was examined. The best process was found for 1.39 mmol dm −3 metronidazole with 0.50 mmol dm −3 Fe 2+ at 55.4 mA cm −2 giving 53% mineralization, 36% mineralization current efficiency and 0.339 kWh (g DOC) −1 in 300 min. Metrodinazole was completely removed and its decay obeyed a pseudo-first-order kinetics. LC-MS analysis allowed identifying five heterocyclic products and twelve hydroxylated derivatives. Ion-exclusion HPLC analysis revealed that final oxalic and oxamic acids were practically removed at the end of electrolysis due to the efficient photolysis of their Fe(III) complexes by sunlight. The initial N of

  4. Boron doped diamond sensor for sensitive determination of metronidazole: Mechanistic and analytical study by cyclic voltammetry and square wave voltammetry

    Energy Technology Data Exchange (ETDEWEB)

    Ammar, Hafedh Belhadj, E-mail: hbelhadjammar@yahoo.fr; 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 pH 11. Under optimal conditions, a linear analytical curve was obtained for the MTZ concentration in the range of 0.2–4.2 μmol L{sup −1}, with a detection limit of 0.065 μmol L{sup −1}. - Highlights: • SWV for the determination of MTZ • Boron-doped diamond as a new electrochemical sensor • Simple and rapid detection of MTZ • Efficiency of BDD for sensitive determination of MTZ.

  5. Boron doped diamond sensor for sensitive determination of metronidazole: Mechanistic and analytical study by cyclic voltammetry and square wave voltammetry

    International Nuclear Information System (INIS)

    Ammar, Hafedh Belhadj; Brahim, Mabrouk Ben; Abdelhédi, Ridha; Samet, Youssef

    2016-01-01

    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 pH 11. Under optimal conditions, a linear analytical curve was obtained for the MTZ concentration in the range of 0.2–4.2 μmol L"−"1, with a detection limit of 0.065 μmol L"−"1. - Highlights: • SWV for the determination of MTZ • Boron-doped diamond as a new electrochemical sensor • Simple and rapid detection of MTZ • Efficiency of BDD for sensitive determination of MTZ

  6. A Meta Analysis of Radiosensitivity on Non-small Cell Lung Cancer 
by Metronidazole Amino Acidum Natrium

    Directory of Open Access Journals (Sweden)

    Weiwei REN

    2012-06-01

    Full Text Available Background and objective The efficacy and safety of radiosensitivity on non-small cell lung cancer (NSCLC using metronidazole amino acidum natrium (CMNa are yet to be proven. This study evaluates the efficacy and safety of radiosensitivity on NSCLC by CMNa to provide references for further clinical practice and research. Methods Relevant randomized controlled trials (RCTs were obtained from the Cochrane library, Pubmed, EMbase, CBM, CNKI, VIP, and Wan Fang databases. Dates were searched through other means. RCTs of radiosensitivity on NSCLC by CMNa were included. The data included in the study were evaluated and analyzed using the Cochrane Collaboration's RevMan 5.1 software. Results A total of 21 RCTs were included. The results of the meta-analyses showed that the total effective rate of the test group that received CMNa plus radiotherapy was higher than that of the control group that received radiotherapy alone (OR=3.29, 95%CI: 2.47-4.39, P<0.000,01 or radiotherapy plus placebo (OR=3.65, 95%CI: 2.25-5.92, P<0.000,01, respectively. No significant differences were found in the quality of life between one and two-year survival rates (P>0.05. No significant differences were found among radiation pneumonitis, radiation esophagitis, hematological toxicity, and cardiotoxicity (P>0.05. Conclusion CMNa plus radiotherapy elicit beneficial effects in the treatment of NSCLC and produce fewer adverse effects. Therefore, this technique can be recommended and applied in clinics.

  7. Extremely High Prevalence of Metronidazole-Resistant Helicobacter pylori Strains in Mountain People (Karen and Hmong) in Thailand.

    Science.gov (United States)

    Vilaichone, Ratha-korn; Ratanachu-Ek, Thawee; Gamnarai, Pornpen; Chaithongrat, Supakarn; Uchida, Tomahisa; Yamaoka, Yoshio; Mahachai, Varocha

    2016-04-01

    This study aimed to survey the prevalence, patterns of antibiotic resistance, and clinical factors associated with antibiotic resistance in Helicobacter pylori among the Karen and Hmong mountain people of Thailand. We recruited dyspeptic patients in the Maesod district, Tak Province, Thailand. All subjects underwent upper gastrointestinal endoscopy, and three antral gastric biopsies were obtained for rapid urease tests and culture. An epsilometer was used to determine the minimum inhibitory concentrations of amoxicillin (AMX), clarithromycin (CLR), metronidazole (MNZ), levofloxacin (LVX), ciprofloxacin (CIP), and tetracycline (TET). A total of 291 subjects were enrolled; 149 (51.2%) were infected with H. pylori. Helicobacter pylori infection was present in 47.1% of Thai, 51.7% of Karen, and 58.7% of Hmong subjects. Antibiotic resistance was present in 75.8% including AMX (0.8%), TET (0%), CLR (5.6%), MNZ (71.8%), CIP (19.4%), LVX (19.4%), and multidrug resistance in 21.8%. Karen subjects had the highest prevalence of MNZ resistance (84.6%), and Hmong subjects had the highest prevalence of fluoroquinolone (27.3%) and multidrug (34.1%) resistance. MNZ plus fluoroquinolone (14.5%) was the most common multidrug resistance. There was no association between clinical factors and antibiotic resistance. MNZ resistance was prevalent, whereas fluoroquinolone- and multidrug-resistant H. pylori infections are important problems in mountain people of Thailand. © The American Society of Tropical Medicine and Hygiene.

  8. Western Diet-Induced Dysbiosis in Farnesoid X Receptor Knockout Mice Causes Persistent Hepatic Inflammation after Antibiotic Treatment.

    Science.gov (United States)

    Jena, Prasant K; Sheng, Lili; Liu, Hui-Xin; Kalanetra, Karen M; Mirsoian, Annie; Murphy, William J; French, Samuel W; Krishnan, Viswanathan V; Mills, David A; Wan, Yu-Jui Yvonne

    2017-08-01

    Patients who have liver cirrhosis and liver cancer also have reduced farnesoid X receptor (FXR). The current study analyzes the effect of diet through microbiota that affect hepatic inflammation in FXR knockout (KO) mice. Wild-type and FXR KO mice were on a control (CD) or Western diet (WD) for 10 months. In addition, both CD- and WD-fed FXR KO male mice, which had hepatic lymphocyte and neutrophil infiltration, were treated by vancomycin, polymyxin B, and Abx (ampicillin, neomycin, metronidazole, and vancomycin). Mice were subjected to morphological analysis as well as gut microbiota and bile acid profiling. Male WD-fed FXR KO mice had the most severe steatohepatitis. FXR KO also had reduced Firmicutes and increased Proteobacteria, which could be reversed by Abx. In addition, Abx eliminated hepatic neutrophils and lymphocytes in CD-fed, but not WD-fed, FXR KO mice. Proteobacteria and Bacteroidetes persisted in WD-fed FXR KO mice even after Abx treatment. Only polymyxin B could reduce hepatic lymphocytes in WD-fed FXR KO mice. The reduced hepatic inflammation by antibiotics was accompanied by decreased free and conjugated secondary bile acids as well as changes in gut microbiota. Our data revealed that Lactococcus, Lactobacillus, and Coprococcus protect the liver from inflammation. Copyright © 2017 American Society for Investigative Pathology. Published by Elsevier Inc. All rights reserved.

  9. Characterization of the interactions of human serum albumin (HSA), gatifloxacin, and metronidazole using spectroscopic and electrochemical methods

    International Nuclear Information System (INIS)

    Fu, Li; Liu, Xiu-fen; Zhou, Qiu-xiang; Zhang, Ji-xiang; Dong, Jing-ya; Wang, Jian-fang

    2014-01-01

    Human serum albumin (HSA), the most abundant protein in blood plasma, is an important carrier for many drugs. Understanding HSA-drug interactions is critical in being able to interpret the distribution and acting mechanisms of these drugs, which is particularly important in the case of multi-drug therapy. In this study, we investigated the interactions between HSA and two commonly used antibiotics, gatifloxacin (GFLX) and metronidazole (MET), in Tris–HCl buffer solution (pH=7.4). The efficacy of the individual drugs (GFLX or MET) and the efficacy of a combination of GFLX and MET were measured using fluorescence spectroscopy, UV absorption spectroscopy, and electrochemical methods. Our results demonstrated that GFLX and MET have a synergistic effect. Briefly, one drug decreased the binding stability with HSA of the other drug, thus increasing the concentration of free drug at the action sites. The interaction of drugs with HSA is a process of complex-formation static quenching. There is approximately one binding site between HSA and the drug (GFLX or MET). The binding distance, r, between the drug and HSA was determined on the basis of the theory of Forster-type non-radiative energy transfer. It was shown that the interaction between the two drugs increased the r-value. Using thermodynamic parameters, we found that the binding of drug-HSA interactions is mainly controlled by electrostatic force. Analysis of the synchronous fluorescence spectrum suggested that the interactions between the drugs have important effects on protein conformation. In conclusion, combining GFLX and MET enhances treatment efficacy. Our study provides a basis to understand the mechanism of the interaction of MET, GFLX and HSA in the human body. - Highlights: • The synergistic effects between MET and GFLX were founed. • The type of interaction between the drugs and HSA was identified

  10. Effect of Periodontal Therapy With Amoxicillin-Metronidazole on Pharyngeal Carriage of Penicillin- and Erythromycin-Resistant Viridans Streptococci.

    Science.gov (United States)

    Mombelli, Andrea; Cionca, Norbert; Almaghlouth, Adnan; Cherkaoui, Abdessalam; Schrenzel, Jacques; Giannopoulou, Catherine

    2016-05-01

    Previous studies have focused on antibiotic resistance of Gram-negative bacteria before and after periodontal therapy. The purpose of this analysis is to assess changes in resistance patterns of the commensal Gram-positive microbiota. The viridans group streptococci (VGS) have been suggested to serve as reservoirs of resistance genes for more pathogenic streptococci and may be implicated in some non-oral infections. In this randomized clinical trial, 80 patients with periodontitis are distributed randomly into two groups. In group A, patients received 375 mg amoxicillin and 500 mg metronidazole three times per day for 7 days during the non-surgical treatment phase (T1). In group B, the antibiotics were administered during the surgical phase (T2). Resistance of VGS to penicillin and erythromycin was determined by the epsilometer test. At baseline, VGS from 12.5% (group A) and 11.8% (group B) of patients had a minimum inhibitory concentration (MIC) >2 μg/mL to penicillin. Three months after T1, VGS from 15.6% and 16.7% of patients had an MIC >2 μg/mL, respectively. Six months after T2 VGS from 5.9% and 5.9% and 12 months after T2 VGS from 6.1% and 6.3% patients had an MIC >2 μg/mL. There was no effect of therapy with antibiotics, administered either in T1 or T2, on the carriage of penicillin-resistant VGS. Erythromycin resistance was high at baseline and remained unchanged throughout the study. MICs for penicillin and erythromycin were correlated (P penicillin or erythromycin.

  11. Eudragit FS 30D as a potential polymer for use in the technology of preparing matrix tablets contain metronidazole – an experimental and mathematical modeling study

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    Letmanski Tomasz

    2015-06-01

    Full Text Available The aim of this study was to examine the usefulness of a pH-dependent copolymer - Eudragit FS - for employment in the technology of preparing modified release metronidazole matrix tablets. In addition, in our work, Eudragit RL and Eudragit RS were included in the composition of some formulations, as well as sodium lauryl sulfate and polysorbate 80. As part of the study of the dissolution test, the similarity coefficient (f2 for the obtained profiles was calculated, and mathematic models were used to estimate the kinetics and mechanism of active substance release. In our work, it was observed that the inclusion of polymer Eudragit FS alone in the tablet composition ensured a modified release of the active substance for 10 h. After this time period, the amount of metronidazole determined in the acceptor fluid was 71% - 81% of the declared dose. Modification of the composition by the addition of surfactants resulted in an increased release of the active substance of up to 98%. This effect was dependent on the type of surfactant and its quantitative ratio to the Eudragit FS. Similar release profiles were obtained for tablets containing Eudragit RS and sodium lauryl sulfate, as well as Eudragit RS and polysorbate 80. Depending on the composition of tablets, metronidazole release proceeded in accordance with either first or second-order kinetics. We calculated as well, that the differing masses of Eudragit FS in the studied formulations correlates with the order of release kinetics (p < 0.002. Such an effect was validated using the Weibull model, wherein, in all the studied formulations, the release rate was seen as a decreasing function of time. An analysis of data according to the Ritger-Peppas model and the Peppas-Sahlin model for some formulations, indicated that the mechanism of active substance release from matrix tablets is diffusion.

  12. Idiopathic Facial Aseptic Granuloma in a 13-Year-Old Boy Dramatically Improved with Oral Doxycycline and Topical Metronidazole: Evidence for a Link with Childhood Rosacea

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    Camille Orion

    2016-07-01

    Full Text Available Idiopathic facial aseptic granuloma (IFAG is a rare, benign pediatric dermatological lesion that occurs in children between 8 months and 13 years of age. The pathogenesis of IFAG is still unclear but it is likely to be associated with granulomatous rosacea in childhood. Here we describe a case of IFAG in a 13-year-old boy who showed a dramatic response to oral doxycycline and topical metronidazole, which supports the hypothesis that IFAG may belong to the spectrum of rosacea.

  13. Efforts for improvement in radiotherapy of cancer using metronidazole with special regard to head and neck. Part of a coordinated programme on improvement of cancer therapy by the combination treatment of conventional radiation and physical and chemical means

    International Nuclear Information System (INIS)

    Patricio, M.B.

    1984-03-01

    A great effort has been expended in the search for means which would be of immediate practical interest to the radiotherapist in order to achieve improvement of the result of cancer treatment. These means include modifiers which are sensitizers to potentiate radiation effects on tumour cells without affecting normal tissue. We started a controlled therapeutic trial on locally advanced head and neck carcinomas using metronidazole. There was good tolerance to metronidazole although improvement of local tumour control with this drug was not observed. We also observed that irradiation with fractions daily gave a better tumour control than single fractions a day

  14. Development and validation of a RP–HPLC method for the quantization studies of metronidazole in tablets and powders dosage forms

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    Elena Gabriela Oltean,

    2011-12-01

    Full Text Available An isocratic high-performance liquid chromatography (HPLC procedure was developed for the quantitative determination of metronidazole in tablets and powders. HPLC separation was carried out by reversed phasechromatography on Kromasil C18 (250 mm x 4.6 mm i.e.; 5 ìm particle size, held in thermostat at 25°C. The mobile phase consisted of methanol/ 0.1% phosphoric acid aq. (20/80v/v, with a flow rate of 1 ml/min and with UV detection at 317 nm. In order to validate the method, the following parameters have been investigated: linearity (r2=0.9999, range, precision, accuracy, specificity, limit of detection and limit of quantification. The described method can be successfully applied for the analysis of the active pharmaceuticalcompound in tablets and powders. This paper aimed to develop and validate an HPLC sensitive applicable method to determine the quantity of metronidazole in tablets and powders, contributing to the quality and safety control of these types of pharmaceutical preparations.

  15. Cloning Mice.

    Science.gov (United States)

    Ogura, Atsuo

    2017-08-01

    Viable and fertile mice can be generated by somatic nuclear transfer into enucleated oocytes, presumably because the transplanted somatic cell genome becomes reprogrammed by factors in the oocyte. The first somatic cloned offspring of mice were obtained by directly injecting donor nuclei into recipient enucleated oocytes. When this method is used (the so-called Honolulu method of somatic cell nuclear transfer [SCNT]), the donor nuclei readily and completely condense within the enucleated metaphase II-arrested oocytes, which contain high levels of M-phase-promoting factor (MPF). It is believed that the condensation of the donor chromosomes promotes complete reprogramming of the donor genome within the mouse oocytes. Another key to the success of mouse cloning is the use of blunt micropipettes attached to a piezo impact-driving micromanipulation device. This system saves a significant amount of time during the micromanipulation of oocytes and thus minimizes the loss of oocyte viability in vitro. For example, a group of 20 oocytes can be enucleated within 10 min by an experienced operator. This protocol is composed of seven parts: (1) preparing micropipettes, (2) setting up the enucleation and injection micropipettes, (3) collecting and enucleating oocytes, (4) preparing nucleus donor cells, (5) injecting donor nuclei, (6) activating embryos and culturing, and (7) transferring cloned embryos. © 2017 Cold Spring Harbor Laboratory Press.

  16. 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.

    Science.gov (United States)

    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.

  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

    Directory of Open Access Journals (Sweden)

    Khadijeh Abdali

    2015-01-01

    Full Text Available 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. Validação de método de doseamento e aplicação em estudo de equivalência farmacêutica de solução injetável de metronidazol

    Directory of Open Access Journals (Sweden)

    FELIPE REBELLO LOURENçO

    2010-06-01

    Full Text Available O presente trabalho tem por objetivos validar métodos por espectrofotometria de absorção no ultravioleta e cromatografia líquida de alta eficiência para o doseamento de metronidazol em solução injetável e aplicá-los em estudo de equivalência farmacêutica entre medicamento de referência, genérico e similar. Os métodos propostos para doseamento de metronidazol em solução injetável por espectrofotometria de absorção no ultravioleta e por cromatografia líquida de alta eficiência foram validados, mostrando especificidade / seletividade, linearidade e faixa linear, limite de detecção / quantificação, exatidão e precisão adequados para o uso pretendido. Os medicamentos foram avaliados quanto aos testes de determinação de pH, volume médio, identificação por espectrofotometria de absorção no infravermelho, identificação por cromatografia líquida de alta eficiência, esterilidade, endotoxinas bacterianas e doseamento por espectrofotometria de absorção no ultravioleta e por cromatografia líquida de alta eficiência. Os três medicamentos atenderam as especificações para os testes avaliados e, portanto, podem ser considerados apresentando equivalência farmacêutica. Palavras-chave: Metronidazol. Equivalência farmacêutica. Validação. Flagyl. ABSTRACT Validation of metronidazole assay methods and application to study of pharmaceutical equivalence of injectable solutions of this drug The aim of this study was to validate analytical methods, based on UV absorption spectrophotometry and high performance liquid chromatography (HPLC, to assay metronidazole supplied in injectable solutions, and to employ these methods in a study of the pharmaceutical equivalence of the original brand name medicine (‘reference’, generic and similar (brand medicines. The methods proposed for the metronidazole assay were validated, showing adequate specificity/selectivity, linearity, linear range, detection and

  19. Use of a lactic acid plus lactoserum intimate liquid soap for external hygiene in the prevention of bacterial vaginosis recurrence after metronidazole oral treatment.

    Science.gov (United States)

    Bahamondes, M Valeria; Portugal, Priscila Mendes; Brolazo, Eliane Melo; Simões, José Antônio; Bahamondes, Luis

    2011-01-01

    To determine the recurrence of bacterial vaginosis (BV) after the use of a lactic acid plus lactoserum liquid soap starting immediately after the treatment with oral metronidazole and the quality of life of the participants. A total of 123 women with diagnosis of BV with at least three of the following criteria: 1) homogeneous vaginal discharge without inflammation of the vagina or vulva; 2) vaginal pH ≥ 4.5; 3) positive Whiff test; and 4) "clue cells" in more than 20% of the epithelial cells in the vagina. A Nugent score ≥ 4 in the vaginal bacterioscopy was also used. After BV diagnosis, metronidazole 500 mg was administered orally bid during 7 days. Patients cured of BV were then instructed to use 7.5 to 10 mL of a lactic acid plus lactoserum liquid soap once-a-day for hygiene of the external genital region. Three subsequent control visits after starting the hygiene treatment (30, 60, and 90 days; ± 5 days) were scheduled. A questionnaire was applied in the form of visual analogue scale (VAS) in all the visits regarding: 1) level of comfort at the genital region; 2) malodorous external genitalia; 3) comfort in sexual intercourse; 4) satisfaction with intimate hygiene; and 5) self-esteem. Ninety two (74.8%) women initiated the use of a lactic acid plus lactoserum liquid soap at visit 1. At visit 2, 3, and 4 there were 84, 62 and 42 women available for evaluation, respectively. The rate of recurrence of BV was 19.0%, 24.2% and 7.1%, respectively in the three visits and vaginal candidiasis was observed in five treated women. Quality of life was evaluated in the 42 women who completed the four visits schedule and there were significant improvement in the five domains assessed. A lactic acid plus lactoserum liquid soap for external intimate hygiene may be an option for the prevention of BV recurrence after treatment and cure with oral metronidazole.

  20. Spectroscopic investigation on assisted sonocatalytic damage of bovine serum albumin (BSA) by metronidazole (MTZ) under ultrasonic irradiation combined with nano-sized ZnO

    Science.gov (United States)

    Gao, Jingqun; Liu, Bin; Wang, Jun; Jin, Xudong; Jiang, Renzheng; Liu, Lijun; Wang, Baoxin; Xu, Yongnan

    2010-11-01

    The previous work proved that the bovine serum albumin (BSA) could be damaged under the combined action of ultrasonic irradiation and ZnO. In this work, the assisted sonocatalytic damage of BSA using metronidazole (MTZ) as a sensitizer was further investigated by means of UV-vis and fluorescence spectra. The results indicated that the adding of MTZ could obviously promote the sonocatalytic damage of BSA under ultrasonic irradiation in the presence of nano-sized ZnO powder. Furthermore, it was found that the damage degree of BSA was aggravated by some influencing factors except ionic kind and strength. In addition, the damage site of BSA was also studied with synchronous fluorescence technology. It was found that the damage site was mainly at tryptophan (Trp) residue.

  1. A prospective cohort study comparing the effect of single-dose 2 g metronidazole on Trichomonas vaginalis infection in HIV-seropositive versus HIV-seronegative women.

    Science.gov (United States)

    Balkus, Jennifer E; Richardson, Barbra A; Mochache, Vernon; Chohan, Vrasha; Chan, Jeannie D; Masese, Linnet; Shafi, Juma; Marrazzo, Jeanne; Farquhar, Carey; McClelland, R Scott

    2013-06-01

    This analysis compared the frequency of persistent Trichomonas vaginalis (TV) among HIV-seropositive and HIV-seronegative women. Data were obtained from women enrolled in an open cohort study of sex workers in Kenya. Participants were examined monthly, and those diagnosed as having TV by saline microscopy were treated with single-dose 2 g oral metronidazole. All women on antiretroviral therapy (ART) used nevirapine-based regimens. Generalized estimating equations with a logit link were used to compare the frequency of persistent TV (defined as the presence of motile trichomonads by saline microscopy at the next examination visit within 60 days) by HIV status. Three-hundred sixty participants contributed 570 infections to the analysis (282 HIV-seropositive and 288 HIV-seronegative). There were 42 (15%) persistent infections among HIV-seropositive participants versus 35 (12%) among HIV-seronegative participants (adjusted odds ratio, 1.14; 95% confidence interval [CI], 0.70-1.87). Persistent TV was highest among HIV-seropositive women using ART (21/64 [33%]) compared with HIV-seropositive women not using ART (21/217 [10%]). Concurrent bacterial vaginosis (BV) at TV diagnosis was associated with an increased likelihood of persistent TV (adjusted odds ratio, 1.90; 95% confidence interval, 1.16-3.09). The frequency of persistent TV infection after treatment with single-dose 2 g oral metronidazole was similar by HIV status. Alternative regimens including multiday antibiotic treatment may be necessary to improve cure rates for women using nevirapine-based ART and women with TV and concurrent BV.

  2. Uso do metronidazol como medicação intracanal em dentes com necrose pulpar e reação periapical: relato de caso = The use of metronidazol as an intracanal medication for teeth with pulpar necrosis and periapical reaction: case report

    Directory of Open Access Journals (Sweden)

    Carneiro, Sérgio Murilo Barbalho de Souza

    2005-01-01

    Full Text Available O objetivo desse trabalho foi comparar dois tratamentos endodônticos realizados em dentes com abscesso periapical crônico, em um mesmo paciente, empregando-se medicações intracanais diferentes. Para isso foram relatados dois casos clínicos de tratamentos endodônticos em dois dentes (31 e 41, nos quais foram empregados a mesma técnica de preparo biomecânico e obturação, variando apenas a medicação intracanal, pois no dente 31 foi empregada uma pasta a base de hidróxido de cálcio (Calen e no dente 41, o metronidazol na forma de gel ginecológico. Após um ano de proservação dos tratamentos realizados, verificou-se reparação dos tecidos periapicais em ambos os dentes, concluindo-se que, nesse caso, a variação da medicação intracanal não interferiu no resultado do tratamento instituído e que o metronidazol pode ser uma alternativa viável como coadjuvante na terapia endodôntica desse tipo de patologia

  3. Metronidazole in conjunction with penicillin neither prevents recurrence nor enhances recovery from peritonsillar abscess when compared with penicillin alone: a prospective, double-blind, randomized, placebo-controlled trial.

    Science.gov (United States)

    Wikstén, Johanna E; Pitkäranta, Anne; Blomgren, Karin

    2016-06-01

    The objectives of this study were to evaluate the efficacy of metronidazole in conjunction with penicillin in preventing the recurrence of peritonsillar abscess (PTA) and to learn whether metronidazole enhances the recovery from PTA when compared with penicillin alone. In this prospective, double-blind, randomized, placebo-controlled trial, 200 adult outpatients with PTA at our ear, nose and throat emergency department received either penicillin (1 000 000IU) × 3 and metronidazole (400 mg) × 3 for 10 and 7 days orally (combination group, N = 100) or penicillin and placebo (penicillin group, N = 100) after incision and drainage of the PTA. Afterwards they received a symptom questionnaire via e-mail daily for 2 weeks, then weekly for 6 weeks. The primary outcome was efficacy of metronidazole in conjunction with penicillin in preventing PTA recurrence in 56 days; the secondary outcome was ability of metronidazole plus penicillin to enhance recovery from PTA in 28 days. All healthcare contacts were registered during follow-up. Registered on www.clinicaltrials.gov with the identifier NCT01255670. Of the 200 patients, 20 returned to hospital with recurrent symptoms, 10 in each group (P = 1.00). In the combination group, the mean (SD) duration of throat-related symptoms was 5.6 (5.0) days and in the penicillin group it was 5.3 (2.7) days, values for fever were 1.5 (0.9) and 1.6 (1.0) days, respectively, and those for poor overall physical condition were 4.0 (3.9) and 4.5 (4.9) days; there were no significant differences between groups. The adverse effects nausea and diarrhoea lasted longer in the combination group (P = 0.01). For healthy adult PTA patients treated with incision and drainage, metronidazole neither prevents recurrence nor enhances recovery when combined with penicillin compared with penicillin alone, but instead leads to increased adverse effects. © The Author 2016. Published by Oxford University Press on behalf of the British

  4. Pre-treatment with antibiotics and Escherichia coli to equalize the gut microbiota in conventional mice.

    Science.gov (United States)

    Linninge, Caroline; Ahrné, Siv; Molin, Göran

    2015-01-01

    The composition of the gut microbiota can vary widely between individual mice of the same batch and thereby affect the resulting outcome in experimental studies. Therefore, an efficient method is needed to equalize the gut microbiota prior to the start of critical experiments. In order to minimize variations in gut microbiota between animals and provide the animals with a Gram-negative flora exposing lipopolysaccharides in the cell-walls, C57BL/6 mice were given a mixture of ampicillin, metronidazole and clindamycin in the drinking water for 3 days and then Escherichia coli for two additional days. Treatment with antibiotics alone or with antibiotics in combination with E. coli was well tolerated by all animals. Body weight and liver weight were not affected, although higher hepatic fat content was found in treated animals (p antibiotics and antibiotics in combination with E. coli (p < 0.01), without affecting the total amount of bacteria. Cloned and sequenced 16S rRNA genes showed high presence of Enterobacteriaceae and Porphymonadaceae in the treated animals. Analysis with Principal Component Analysis gave a clear separation of the composition in microbiota between different treatment groups. The described treatment efficiently equalized the gut microbiota and provided the animals with a strong abundance of Enterobacteriaceae without changing the total load of bacteria. This is a straightforward, lenient and efficient method of pre-treatment to equalize the gut microbiota of mice as a starting procedure of animal studies.

  5. Efficacy of oral metronidazole with vaginal clindamycin or vaginal probiotic for bacterial vaginosis: randomised placebo-controlled double-blind trial.

    Directory of Open Access Journals (Sweden)

    Catriona S Bradshaw

    Full Text Available BACKGROUND: To determine if oral metronidazole (MTZ-400 mg bid with 2% vaginal clindamycin-cream (Clind or a Lactobacillus acidophilus vaginal-probiotic containing oestriol (Prob reduces 6-month bacterial vaginosis (BV recurrence. METHODS: Double-blind placebo-controlled parallel-group single-site study with balanced randomization (1:1:1 conducted at Melbourne Sexual Health Centre, Australia. Participants with symptomatic BV [Nugent Score (NS = 7-10 or ≥3 Amsel's criteria and NS = 4-10], were randomly allocated to MTZ-Clind, MTZ-Prob or MTZ-Placebo and assessed at 1,2,3 and 6 months. MTZ and Clind were administered for 7 days and Prob and Placebo for 12 days. Primary outcome was BV recurrence (NS of 7-10 on self-collected vaginal-swabs over 6-months. Cumulative BV recurrence rates were compared between groups by Chi-squared statistics. Kaplan-Meier, log rank and Cox regression analyses were used to compare time until and risk of BV recurrence between groups. RESULTS: 450 18-50 year old females were randomized and 408 (91%, equally distributed between groups, provided ≥1 NS post-randomization and were included in analyses; 42 (9% participants with no post-randomization data were excluded. Six-month retention rates were 78% (n = 351. One-month BV recurrence (NS 7-10 rates were 3.6% (5/140, 6.8% (9/133 and 9.6% (13/135 in the MTZ-Clind, MTZ-Prob and MTZ-Placebo groups respectively, p = 0.13. Hazard ratios (HR for BV recurrence at one-month, adjusted for adherence to vaginal therapy, were 0.43 (95%CI 0.15-1.22 and 0.75 (95% CI 0.32-1.76 in the MTZ-Clind and MTZ-Prob groups compared to MTZ-Plac respectively. Cumulative 6-month BV recurrence was 28.2%; (95%CI 24.0-32.7% with no difference between groups, p = 0.82; HRs for 6-month BV recurrence for MTZ-Clind and MTZ-Prob compared to MTZ-Plac, adjusted for adherence to vaginal therapy were 1.09(95% CI = 0.70-1.70 and 1.03(95% CI = 0.65-1.63, respectively. No serious

  6. Facile synthesis and high activity of novel BiVO{sub 4}/FeVO{sub 4} heterojunction photocatalyst for degradation of metronidazole

    Energy Technology Data Exchange (ETDEWEB)

    Li, Jinhai [State Key Laboratory of Pollution Control and Resource Reuse, School of the Environment, Nanjing University, Nanjing 210023 (China); School of Chemical Engineering, Guizhou University of Engineering Science, Bijie 551700 (China); Zhao, Wei; Guo, Yang; Wei, Zhongbo; Han, Mengshu [State Key Laboratory of Pollution Control and Resource Reuse, School of the Environment, Nanjing University, Nanjing 210023 (China); He, Huan [State Key Laboratory of Pollution Control and Resource Reuse, School of the Environment, Nanjing University, Nanjing 210023 (China); School of Public Health, University of Illinois at Chicago, Chicago, IL 60631 (United States); Yang, Shaogui [State Key Laboratory of Pollution Control and Resource Reuse, School of the Environment, Nanjing University, Nanjing 210023 (China); Department of Plant, Soil and Microbial Sciences, Michigan State University, East Lansing, Michigan 48824 (United States); Sun, Cheng, E-mail: envidean@nju.edu.cn [State Key Laboratory of Pollution Control and Resource Reuse, School of the Environment, Nanjing University, Nanjing 210023 (China)

    2015-10-01

    Graphical abstract: - Highlights: • BiVO{sub 4}/FeVO{sub 4} was synthesized by a facile one-step hydrothermal method. • BiVO{sub 4}/FeVO{sub 4} displays superior photocatalytic activity. • The photocatalytic mechanism were discussed in detail. - Abstract: The novel BiVO{sub 4}/FeVO{sub 4} heterojunction photocatalyst was successfully synthesized by a facile hydrothermal method firstly. The physical and chemical properties of as-prepared samples were characterized based upon XRD, XPS, BET, SEM, EDS, TEM, UV–vis DRS and fluorescence spectrum techniques. The TEM images showed a clear interface between BiVO{sub 4} and FeVO{sub 4}, indicating that a heterojunction between BiVO{sub 4} and FeVO{sub 4} was formed during the hydrothermal reaction. In addition, the photodegradation activity of metronidazole (MNZ) was used as a measurement for photocatalytic performance of BiVO{sub 4}, FeVO{sub 4} and BiVO{sub 4}/FeVO{sub 4} heterojunction photocatalyst. It indicated that under visible light irradiation the photocatalytic activity of BiVO{sub 4}/FeVO{sub 4} heterojunction photocatalyst was very effective, and moreover, much higher than the single BiVO{sub 4} or single FeVO{sub 4}. The possible photocatalytic mechanism has been discussed on the basis of the theoretical calculation of the electronic structure, and the experimental results.

  7. Folliculitis et perifolliculitis capitis abscedens et suffodiens controlled with a combination therapy: Systemic antibiosis (Metronidazole Plus Clindamycin, dermatosurgical approach, and high-dose isotretinoin

    Directory of Open Access Journals (Sweden)

    Georgi Tchernev

    2011-01-01

    Full Text Available Folliculitis et perifolliculitis capitis abscedens et suffodiens is a rare disease of unknown etiology. It is a suppurative process that involves the scalp, eventually resulting in extensive scarring and irreversible alopecia. The condition is also known as ′acne necrotica miliaris′ or ′Proprionibacterium′ folliculitis. Most often the disease affects men of African-American or African-Caribbean descent between 20 and 40 years of age. The clinical picture is determined by fluctuating painful fistule-forming conglomerates of abscesses in the region of the occipital scalp. The cause of scalp folliculitis is not well understood. It is generally considered to be an inflammatory reaction to components of the hair follicle, particularly the micro-organisms. These include: bacteria (especially Propionibacterium acnes, but in severe cases, also Staphylococcus aureus, Yeasts (Malassezia species and mites (Demodex folliculorum. The initial histopathologic finding is an exclusively neutrophilic infiltration followed by a granulomatous infiltrate. The treatment of the disease is usually difficult and often disappointing. Successful treatment with isotretinoin 1 mg/kg body mass could be achieved only after regular systematic administration in the course of 3-4 months. Here we describe a patient with eruptive purulent form of the disease, which has been controlled with combination therapy: systemic antibiosis with metronidazole and clindamycin, dermatosurgical removal of single nodular formations, and isotretinoin 1 mg/kg body mass for 3-5 months.

  8. Human Lysozyme Synergistically Enhances Bactericidal Dynamics and Lowers the Resistant Mutant Prevention Concentration for Metronidazole to Helicobacter pylori by Increasing Cell Permeability

    Directory of Open Access Journals (Sweden)

    Xiaolin Zhang

    2016-10-01

    Full Text Available Metronidazole (MNZ is an effective agent that has been employed to eradicate Helicobacter pylori (H. pylori. The emergence of broad MNZ resistance in H. pylori has affected the efficacy of this therapeutic agent. The concentration of MNZ, especially the mutant prevention concentration (MPC, plays an important role in selecting or enriching resistant mutants and regulating therapeutic effects. A strategy to reduce the MPC that can not only effectively treat H. pylori but also prevent resistance mutations is needed. H. pylori is highly resistant to lysozyme. Lysozyme possesses a hydrolytic bacterial cell wall peptidoglycan and a cationic dependent mode. These effects can increase the permeability of bacterial cells and promote antibiotic absorption into bacterial cells. In this study, human lysozyme (hLYS was used to probe its effects on the integrity of the H. pylori outer and inner membranes using as fluorescent probe hydrophobic 1-N-phenyl-naphthylamine (NPN and the release of aspartate aminotransferase. Further studies using a propidium iodide staining method assessed whether hLYS could increase cell permeability and promote cell absorption. Finally, we determined the effects of hLYS on the bactericidal dynamics and MPC of MNZ in H. pylori. Our findings indicate that hLYS could dramatically increase cell permeability, reduce the MPC of MNZ for H. pylori, and enhance its bactericidal dynamic activity, demonstrating that hLYS could reduce the probability of MNZ inducing resistance mutations.

  9. A randomized treatment trial: single versus 7-day dose of metronidazole for the treatment of Trichomonas vaginalis among HIV-infected women.

    Science.gov (United States)

    Kissinger, Patricia; Mena, Leandro; Levison, Judy; Clark, Rebecca A; Gatski, Megan; Henderson, Harold; Schmidt, Norine; Rosenthal, Susan L; Myers, Leann; Martin, David H

    2010-12-15

    To determine if the metronidazole (MTZ) 2-gm single dose (recommended) is as effective as the 7-day 500 mg twice a day dose (alternative) for treatment of Trichomonas vaginalis (TV) among HIV+ women. Phase IV randomized clinical trial; HIV+ women with culture confirmed TV were randomized to treatment arm: MTZ 2-gm single dose or MTZ 500 mg twice a day 7-day dose. All women were given 2-gm MTZ doses to deliver to their sex partners. Women were recultured for TV at a test-of-cure (TOC) visit occurring 6-12 days after treatment completion. TV-negative women at TOC were again recultured at a 3-month visit. Repeat TV infection rates were compared between arms. Two hundred seventy HIV+/TV+ women were enrolled (mean age = 40 years, ±9.4; 92.2% African American). Treatment arms were similar with respect to age, race, CD4 count, viral load, antiretroviral therapy status, site, and loss-to-follow up. Women in the 7-day arm had lower repeat TV infection rates at TOC [8.5% (11 of 130) versus 16.8% (21 of 125) (relative risk: 0.50, 95% confidence interval = 0.25, 1.00; P TV among HIV+ women.

  10. Outcome evaluation of clarithromycin, metronidazole and lansoprazole regimens in Helicobacter pylori positive or negative children with resistant otitis media with effusion.

    Science.gov (United States)

    Mel-Hennawi, D; Ahmed, M R

    2015-11-01

    To compare the efficacy of two treatment regimens among Helicobacter pylori stool antigen positive children suffering from resistant otitis media with effusion. The study comprised 258 children with bilateral otitis media with effusion; 134 were positive for H pylori stool antigen, and were equally and randomly allocated to the control group or study group. The control group received standard otitis media with effusion therapy (amoxicillin and clavulanate), while the study group received standard H pylori triple therapy (clarithromycin, metronidazole and lansoprazole). In the control group, there was a marked clinical response to treatment in 33 of the 67 children (49.3 per cent). In the study group, there was a marked response in a significantly higher number of children (46 out of 67, 68.7 per cent). The 124 H pylori stool antigen negative children not included in the 2 aforementioned groups received amoxicillin and clavulanate, and a marked response in symptoms was evident in 98 of these children (79 per cent). H pylori infection may lead to resistance to traditional otitis media with effusion treatment in some cases. H pylori eradication is associated with a high cure rate.

  11. Immunosuppression by hypoxic cell radiosensitizers: a phenomenon of potential clinical importance

    International Nuclear Information System (INIS)

    Rockwell, S.; Kapp, D.S.

    1982-01-01

    The nitroimidazoles metronidazole, misonidazol, and desmethyl misonidazole are currently undergoing clinical trials as possible adjuncts to radiotherapy. Ongoing clinical trials are evaluating the effectiveness of these agents and also documenting the pharmacokinetics and toxicities of radiosensitizing doses of these drugs in man. A variety of toxic effects have been noted in man, including anorexia, nausea and vomiting, peripheral neuropathy, central nervous system symptoms, ototoxicity, allergy, and fear. Laboratory studies have also suggested that these agents have potential to be mutagenic, carcinogenic, and teratogenic. In the editorial presented, the author attempts to draw attention to an additional toxic effect of nitroimidazoles - the inhibition of cell-mediated immune responses

  12. Influence of anoxic sensitizers on the radiation damage in biologically active DNA in aqueous solution

    International Nuclear Information System (INIS)

    Lafleur, M.V.M.; Loman, H.

    1982-01-01

    The competition between biologically active single-stranded phiX174 DNA and the anoxic radiosensitizers metronidazole, misonidazole, paranitroacetophenone or nifuroxime for OH radicals is studied. The results are compared with experiments in which the protection of the DNA by t-butanol is determined. Also the effects of the sensitizers on the chemical nature of the damage (immediate and potential break, immediate and potential base damage) is studied. It is found that in diluted aqueous solutions of DNA these radiosensitizers do not sensitize with respect to the biological inactivation. The only effect observed is a shift from potential to immediate breaks with misonidazole and also nifuroxime. (author)

  13. New antimicrobial nitrofuran, trans-5-amino-3-[2-(5-nitro-2-furyl)vinyl]-delta2-1,2,4-oxadiazole: antimicrobial efficacy in mice, rats, and guinea pigs.

    Science.gov (United States)

    McRipley, R J; Gadebusch, H H; Pansy, F; Semar, R

    1974-09-01

    A new antimicrobial nitrofuran designated SQ 18,506 showed some therapeutic activity when administered orally to mice infected with Escherichia coli, Salmonella schottmuelleri, Shigella flexneri, or Klebsiella pneumoniae. Animals infected parenterally with Streptococcus pyogenes, Proteus mirabilis, Mycobacterium tuberculosis, and Candida albicans, or topically with Trichophyton mentagrophytes, did not respond to therapy with the drug at the dosage levels used. The compound was as effective as metronidazole in the topical treatment of experimental trichomonal infections in mice and in guinea pigs and as effective as nystatin, candicidin, or a sulfanilamide-aminacrine hydrochloride cream in the treatment of a candidal vaginal infection in rats. The chemotherapeutic efficacy of SQ 18,506 in experimental vaginitis caused by Escherichia coli in the rat surpassed that shown by four commercial products available for the treatment of bacterial vaginitis.

  14. New Antimicrobial Nitrofuran, trans-5-Amino-3-[2-(5-Nitro-2-Furyl)Vinyl]-Δ2 -1,2,4-Oxadiazole: Antimicrobial Efficacy in Mice, Rats, and Guinea pigs

    Science.gov (United States)

    McRipley, R. J.; Gadebusch, H. H.; Pansy, F.; Semar, R.

    1974-01-01

    A new antimicrobial nitrofuran designated SQ 18,506 showed some therapeutic activity when administered orally to mice infected with Escherichia coli, Salmonella schottmuelleri, Shigella flexneri, or Klebsiella pneumoniae. Animals infected parenterally with Streptococcus pyogenes, Proteus mirabilis, Mycobacterium tuberculosis, and Candida albicans, or topically with Trichophyton mentagrophytes, did not respond to therapy with the drug at the dosage levels used. The compound was as effective as metronidazole in the topical treatment of experimental trichomonal infections in mice and in guinea pigs and as effective as nystatin, candicidin, or a sulfanilamide-aminacrine hydrochloride cream in the treatment of a candidal vaginal infection in rats. The chemotherapeutic efficacy of SQ 18,506 in experimental vaginitis caused by Escherichia coli in the rat surpassed that shown by four commercial products available for the treatment of bacterial vaginitis. PMID:15830472

  15. Iron doped SnO{sub 2}/Co{sub 3}O{sub 4} nanocomposites synthesized by sol-gel and precipitation method for metronidazole antibiotic degradation

    Energy Technology Data Exchange (ETDEWEB)

    Agarwal, Shilpi [Department of Applied Chemistry, University of Johannesburg, Johannesburg (South Africa); Tyagi, Inderjeet [Department of Chemistry, Indian Institute of Technology Roorkee, 247667 (India); Gupta, Vinod Kumar, E-mail: vinodg@uj.ac.za [Department of Applied Chemistry, University of Johannesburg, Johannesburg (South Africa); Sohrabi, Maryam; Mohammadi, Sanaz [Department of Chemistry, Shahr-e-Qods Branch, Islamic Azad University, Tehran (Iran, Islamic Republic of); Golikand, Ahmad Nozad, E-mail: anozad@aeoi.org.ir [Department of Chemistry, Shahr-e-Qods Branch, Islamic Azad University, Tehran (Iran, Islamic Republic of); Jaber Research Laboratory, NSTRI, P.O. Box: 14395-836, Tehran (Iran, Islamic Republic of); Fakhri, Ali, E-mail: ali.fakhri88@yahoo.com [Young Researchers and Elites Club, Science and Research Branch, Islamic Azad University, Tehran (Iran, Islamic Republic of)

    2017-01-01

    Sol-gel and precipitation reaction methods were used to synthesize Un-doped and Fe-doped SnO{sub 2}/Co{sub 3}O{sub 4} nanocomposites under UV light; the synthesized nanocomposites were applied for the photocatalytic degradation of metronidazole antibiotic. The developed photo catalyst was well characterized using energy dispersive X-ray spectrometer (EDX), X-ray diffraction (XRD), vibrating sample magnetometer (VSM), field emission scanning electron microscopy (FE-SEM), UV–Visible and photoluminescence (PL) spectroscopy. Effective parameters such as pH, photocatalyst dose and contact time was optimized and well investigated. From the obtained facts it is clear that the 98.3% of MTZ was degraded with in 15 min, pH 6 and 0.1 g catalyst when the Fe molar ratio was 1:1 at %. As compared to results obtained from un-doped SnO{sub 2}/Co{sub 3}O{sub 4} nanocomposites Fe doped SnO{sub 2}/Co{sub 3}O{sub 4} nanocomposites possess greater photocatalytic efficiency. - Graphical abstract: Surface textural and morphological presentation. - Highlights: • Un-doped and Fe-doped SnO{sub 2}/Co{sub 3}O{sub 4} nanocomposites were applied as photocatalyst. • The nanocomposites exhibited photocatalytic property under UV light. • The maximum degradation was observed for Fe-doped SnO{sub 2}/Co{sub 3}O{sub 4} (1:1) photocatalyst. • 0.1 g photocatalyst is sufficient to carry out 98.3% degradation of MTZ.

  16. 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).

    Science.gov (United States)

    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. Copyright © 2014 Elsevier B.V. All rights reserved.

  17. Conjugation of metronidazole with dextran: a potential pharmaceutical strategy to control colonic distribution of the anti-amebic drug susceptible to metabolism by colonic microbes.

    Science.gov (United States)

    Kim, Wooseong; Yang, Yejin; Kim, Dohoon; Jeong, Seongkeun; Yoo, Jin-Wook; Yoon, Jeong-Hyun; Jung, Yunjin

    2017-01-01

    Metronidazole (MTDZ), the drug of choice for the treatment of protozoal infections such as luminal amebiasis, is highly susceptible to colonic metabolism, which may hinder its conversion from a colon-specific prodrug to an effective anti-amebic agent targeting the entire large intestine. Thus, in an attempt to control the colonic distribution of the drug, a polymeric colon-specific prodrug, MTDZ conjugated to dextran via a succinate linker (Dex-SA-MTDZ), was designed. Upon treatment with dextranase for 8 h, the degree of Dex-SA-MTDZ depolymerization (%) with a degree of substitution (mg of MTDZ bound in 100 mg of Dex-SA-MTDZ) of 7, 17, and 30 was 72, 38, and 8, respectively, while that of dextran was 85. Depolymerization of Dex-SA-MTDZ was found to be necessary for the release of MTDZ, because dextranase pretreatment ensures that de-esterification occurs between MTDZ and the dextran backbone. In parallel, Dex-SA-MTDZ with a degree of substitution of 17 was found not to release MTDZ upon incubation with the contents of the small intestine and stomach of rats, but it released MTDZ when incubated with rat cecal contents (including microbial dextranases). Moreover, Dex-SA-MTDZ exhibited prolonged release of MTDZ, which contrasts with drug release by small molecular colon-specific prodrugs, MTDZ sulfate and N -nicotinoyl-2-{2-(2-methyl-5-nitroimidazol-1-yl)ethyloxy}-d,l-glycine. These prodrugs were eliminated very rapidly, and no MTDZ was detected in the cecal contents. Consistent with these in vitro results, we found that oral gavage of Dex-SA-MTDZ delivered MTDZ (as MTDZ conjugated to [depolymerized] dextran) to the distal colon. However, upon oral gavage of the small molecular prodrugs, no prodrugs were detected in the distal colon. Collectively, these data suggest that dextran conjugation is a potential pharmaceutical strategy to control the colonic distribution of drugs susceptible to colonic microbial metabolism.

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

    Directory of Open Access Journals (Sweden)

    Yunsong Liu

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

  19. Of mice and men

    CERN Multimedia

    1973-01-01

    At the end of March , sixty mice were irradiated at the synchro-cyclotron in the course of an experimental programme studying radiation effects on mice and plants (Vicia faba bean roots) being carried out by the CERN Health Physics Group.

  20. In vitro dissolution of generic immediate-release solid oral dosage forms containing BCS class I drugs: comparative assessment of metronidazole, zidovudine, and amoxicillin versus relevant comparator pharmaceutical products in South Africa and India.

    Science.gov (United States)

    Reddy, Nallagundla H S; Patnala, Srinivas; Löbenberg, Raimar; Kanfer, Isadore

    2014-10-01

    Biowaivers are recommended for immediate-release solid oral dosage forms using dissolution testing as a surrogate for in vivo bioequivalence studies. Several guidance are currently available (the World Health Organization (WHO), the US FDA, and the EMEA) where the conditions are described. In this study, definitions, criteria, and methodologies according to the WHO have been applied. The dissolution performances of immediate-release metronidazole, zidovudine, and amoxicillin products purchased in South African and Indian markets were compared to the relevant comparator pharmaceutical product (CPP)/reference product. The dissolution performances were studied using US Pharmacopeia (USP) apparatus 2 (paddle) set at 75 rpm in each of three dissolution media (pH1.2, 4.5, and 6.8). Concentrations of metronidazole, zidovudine, and amoxicillin in each dissolution media were determined by HPLC. Of the 11 metronidazole products tested, only 8 could be considered as very rapidly dissolving products as defined by the WHO, whereas 2 of those products could be considered as rapidly dissolving products but did not comply with the f 2 acceptance criteria in pH 6.8. All 11 zidovudine products were very rapidly dissolving, whereas in the case of the 14 amoxicillin products tested, none of those products met any of the WHO criteria. This study indicates that not all generic products containing the same biopharmaceutics classification system (BCS) I drug and in similar strength and dosage form are necessarily in vitro equivalent. Hence, there is a need for ongoing market surveillance to determine whether marketed generic products containing BCS I drugs meet the release requirements to confirm their in vitro bioequivalence to the respective reference product.

  1. The MICE Online Systems

    CERN Multimedia

    CERN. Geneva

    2012-01-01

    The Muon Ionization Cooling Experiment (MICE) is designed to test transverse cooling of a muon beam, demonstrating an important step along the path toward creating future high intensity muon beam facilities. Protons in the ISIS synchrotron impact a titanium target, producing pions which decay into muons that propagate through the beam line to the MICE cooling channel. Along the beam line, particle identification (PID) detectors, scintillating fiber tracking detectors, and beam diagnostic tools identify and measure individual muons moving through the cooling channel. The MICE Online Systems encompass all tools; including hardware, software, and documentation, within the MLCR (MICE Local Control Room) that allow the experiment to efficiently record high quality data. Controls and Monitoring (C&M), Data Acquisition (DAQ), Online Monitoring and Reconstruction, Data Transfer, and Networking all fall under the Online Systems umbrella. C&M controls all MICE systems including the target, conventional an...

  2. Loss of angiopoietin-like 4 (ANGPTL4) in mice with diet-induced obesity uncouples visceral obesity from glucose intolerance partly via the gut microbiota.

    Science.gov (United States)

    Janssen, Aafke W F; Katiraei, Saeed; Bartosinska, Barbara; Eberhard, Daniel; Willems van Dijk, Ko; Kersten, Sander

    2018-06-01

    Angiopoietin-like 4 (ANGPTL4) is an important regulator of triacylglycerol metabolism, carrying out this role by inhibiting the enzymes lipoprotein lipase and pancreatic lipase. ANGPTL4 is a potential target for ameliorating cardiometabolic diseases. Although ANGPTL4 has been implicated in obesity, the study of the direct role of ANGPTL4 in diet-induced obesity and related metabolic dysfunction is hampered by the massive acute-phase response and development of lethal chylous ascites and peritonitis in Angptl4 -/- mice fed a standard high-fat diet. The aim of this study was to better characterise the role of ANGPTL4 in glucose homeostasis and metabolic dysfunction during obesity. We chronically fed wild-type (WT) and Angptl4 -/- mice a diet rich in unsaturated fatty acids and cholesterol, combined with fructose in drinking water, and studied metabolic function. The role of the gut microbiota was investigated by orally administering a mixture of antibiotics (ampicillin, neomycin, metronidazole). Glucose homeostasis was assessed via i.p. glucose and insulin tolerance tests. Mice lacking ANGPTL4 displayed an increase in body weight gain, visceral adipose tissue mass, visceral adipose tissue lipoprotein lipase activity and visceral adipose tissue inflammation compared with WT mice. However, they also unexpectedly had markedly improved glucose tolerance, which was accompanied by elevated insulin levels. Loss of ANGPTL4 did not affect glucose-stimulated insulin secretion in isolated pancreatic islets. Since the gut microbiota have been suggested to influence insulin secretion, and because ANGPTL4 has been proposed to link the gut microbiota to host metabolism, we hypothesised a potential role of the gut microbiota. Gut microbiota composition was significantly different between Angptl4 -/- mice and WT mice. Interestingly, suppression of the gut microbiota using antibiotics largely abolished the differences in glucose tolerance and insulin levels between WT and Angptl4

  3. Dwarf Mice and Aging.

    Science.gov (United States)

    Masternak, Michal M; Darcy, Justin; Victoria, Berta; Bartke, Andrzej

    2018-01-01

    Dwarf mice have been studied for many decades, however, the focus of these studies shifted in 1996 when it was shown by Brown-Borg and her coworkers that Ames dwarf (Prop1 df ) mice are exceptionally long-lived. Since then, Snell dwarf (Pit1 dw ) and growth hormone receptor knockout (GHR-KO, a.k.a. Laron dwarf) mice were also shown to be exceptionally long-lived, presumably due to their growth hormone (GH)-deficiency or -resistance, respectively. What is of equal importance in these dwarf mice is their extended health span, that is, these animals have a longer period of life lived free of frailty and age-related diseases. This review article focuses on recent studies conducted in these dwarf mice, which concerned brown and white adipose tissue biology, microRNA (miRNA) profiling, as well as early-life dietary and hormonal interventions. Results of these studies identify novel mechanisms linking reduced GH action with extensions of both life span and health span. Copyright © 2017. Published by Elsevier Inc.

  4. 甲硝唑及双氢青蒿素对阴道毛滴虫抗虫效果观察%The Effects of Metronidazole and Dihydroartemisinin on Trichomonas Vaginalis in vitro

    Institute of Scientific and Technical Information of China (English)

    杨树国; 郭鄂平; 王娅

    2014-01-01

    目的:测定阴道毛滴虫十堰分离株对甲硝唑的敏感性,并观察双氢青蒿素对甲硝唑低敏感株的抗虫效果.方法:自2009年至2011年,从湖北医药学院附属太和医院妇科门诊收集25株阴道毛滴虫临床分离株,体外纯化培养传代,测定292.1、182.6、146.1、91.3、45.6、22.8、11.4、5.7 μmol/L甲硝唑浓度下4、8、12、24 h时间点滴虫死亡率,获取各虫株24h最低致死量(Minimum lethal concentration,MLC).对24 h MLC大于22.8 μmol/L的虫株进行抗虫实验,测定5.3、3.5和1.8 mmol/L双氢青蒿素浓度下4、8、12、24h时间点滴虫死亡率,获取24 h MLC.结果:25株滴虫中,24株对甲硝唑较敏感,24 h MLC为11.4 ~ 22.8 μmol/L,1株滴虫为22.8 ~ 45.6 μmol/L.在22.8和45.6 μmol/L浓度作用下,该株滴虫24h死亡率无差异(P>0.05);该株滴虫在3.5和5.3 mmol/L双氢青蒿素浓度作用下,4、8、12 h死亡率有统计学意义(P<0.05),24 h MLC约为3.5 ~5.3 mmol/L.结论:阴道毛滴虫十堰分离株对甲硝唑总体较敏感,但存在个别虫株敏感性下降,双氢青蒿素对甲硝唑低敏感株抗虫效果较好,体外有效杀虫浓度为3.5 ~5.3 mmol/L.%Objective To analyze the sensitivity of trichomonas vaginalis strains isolated in Shiyan district to metronidazole,to study the effect of Dihydroartemisinin (DHA) on low sensitive strains of metronidazole in vitro.Methods From 2009 to 2011,total 25 strains of trichomonas vaginalis were isolated from gynecological clinic service in Taihe hospital,and then cultured and purified in vitro.All the strains was administrated by metronidazole with concentrations of 292.1,182.6,146.1,91.3,45.6,22.8,1 1.4,5.7 μmol/L,and then the death rate of strains were determined at 4,8,12,24 h,respectively.The minimum lethal concentration(MLC) in all 25 strains were analyzed in the given time.If the MLC of the strain in 24 h was much more than 22.8 μmol/L,the death rate of the strain should be determined after treatment

  5. Role of tumor size in radiotherapy using modifiers

    International Nuclear Information System (INIS)

    Kozin, S.V.; Furmanchuk, A.V.

    1990-01-01

    Consideration is given to present-day knowledge about changes, taking place in malignant tumor tissues during their growth, important for results of radiotherapy, using modifiers, from a radiobiological viewpoint. It is shown that hypertermia (HT) is the most effective adjuvant of radiotherapy for medium - and large-size tumors. The combined application of artificial hyperglycemia (AH) and HT is investigated as the method for increasing efficiency of radiotherapy. Efficiency of using radioprotectors and electron-acceptor compounds (metronidazole, misonidazole) for large-size malignant tumors in combinations-metronidazole with AH and misonidazole with HT-is noted. Analysis of these data on radiotherapy efficiency depending on size of irradiated tumors will enable an evaluation of radiotherapy potential in different cases in determining the advisability of modifier application

  6. Birinci basamak Helikobakter pilori eradikasyon tedavisinde 7 ve 14 günlük lansoprazol, amoksisilin, metronidazol protokolünün karşılaştırılması

    OpenAIRE

    UYGUN, Ahmet; KANTARCIOĞLU, Murat; POLAT, Zülfikar; KİLCİLER, Güldem; GÜLŞEN, Mustafa

    2010-01-01

    Giriş ve Amaç: Ülkemizde günümüzde birinci basamak Helikobakter pilori eradikasyon tedavisinde protokollerin süresi ve eradikasyon oranları konusunda tartışmalar sürmektedir. Bu çalışmadaki amacımız; nonülser dispepsili Helikobakter pilori pozitif hastalarda lansoprazol, amoksisilin, metronidazol'den oluşan 7 ve 14 günlük tedavi protokollerinin eradikasyon oranlarını karşılaştırmaktır. Gereç ve Yöntem: Çalışmaya Helikobakter pilori pozitif nonülser dispepsili 180 hasta (84 kadın,...

  7. Of mice and men

    DEFF Research Database (Denmark)

    Andersen, Troels Askhøj; Troelsen, Karin de Linde Lind; Larsen, Lars Allan

    2014-01-01

    CHD is part of the phenotype. Furthermore, mapping of genomic copy number variants and exome sequencing of CHD patients have led to the identification of a large number of candidate disease genes. Experiments in animal models, particularly in mice, have been used to verify human disease genes...

  8. Docetaxel chronopharmacology in mice.

    Science.gov (United States)

    Tampellini, M; Filipski, E; Liu, X H; Lemaigre, G; Li, X M; Vrignaud, P; François, E; Bissery, M C; Lévi, F

    1998-09-01

    Docetaxel tolerance and antitumor efficacy could be enhanced if drug administration was adapted to circadian rhythms. This hypothesis was investigated in seven experiments involving a total of 626 male B6D2F1 mice, synchronized with an alternation of 12 h of light and 12 h of darkness (12:12), after i.v. administration of docetaxel. In experiment (Exp) 1, the drug was given once a week (wk) for 6 wks (20 mg/kg/wk) or for 5 wks (30 mg/kg/wk) at one of six circadian times, during light when mice were resting [3, 7, or 11 hours after light onset (HALO)], or during darkness, when mice were active (15, 19, or 23 HALO). Endpoints were survival and body weight change. In Exp 2 and 3, docetaxel (30 mg/kg/wk) was administered twice, 1 wk apart, at one of four circadian stages (7, 11, 19, or 23 HALO). Endpoints were hematological and intestinal toxicities. In Exp 4, circadian changes in cell cycle phase distribution and BCL-2 immunofluorescence were investigated in bone marrow as possible mechanisms of docetaxel tolerability rhythm. In Exp 5 to 7, docetaxel was administered to mice bearing measurable P03 pancreatic adenocarcinoma (270-370 mg), with tumor weight and survival as endpoints. Mice from Exp 5 and 6 received a weekly schedule of docetaxel at one of six circadian stages (20 or 30 mg/kg/wk at 3, 7, 11, 15, 19, or 23 HALO). In Exp 7, docetaxel (30 mg/kg) was given every 2 days (day 1, 3, 5 schedule) at 7, 11, 19, or 23 HALO. Docetaxel dosing in the second half of darkness (19 or 23 HALO) resulted in significantly worse toxicity than its administration during the light span (3, 7, or 11 HALO). The survival rate ranged from 56.3% in the mice treated at 23 HALO to 93.8 or 87.5% in those injected at 3 or 11 HALO, respectively (Exp 1, P active at 11 HALO (percentage increase in life span, 390%) and least active at 23 HALO (210%). Docetaxel tolerability and antitumor efficacy were simultaneously enhanced by drug dosing in the light span, when mice were resting. Mechanisms

  9. Mycoplasma hominis Symbiosis and Trichomonas vaginalis Metronidazole Resistance%人型支原体共生与阴道毛滴虫甲硝唑耐药性的关系

    Institute of Scientific and Technical Information of China (English)

    王频佳; 谢成彬

    2012-01-01

    目的 研究人型支原体(Mycoplasma hominis)的共生与阴道毛滴虫(Trichomonas vaginalis)甲硝唑耐药性的关系.方法 2010年11月至2011年7月,自四川省妇幼保健院妇科门诊患者生殖道分泌物中分离出160株阴道毛滴虫,用梯度浓度1 024、512、256……4、2和1 μg/ml甲硝唑分别处理该批虫株,以死亡率≥90%的最低浓度作为甲硝唑最小致死浓度(MLC).以160个阴道毛滴虫分离株中提取的DNA为模板,用PCR技术特异性扩增人型支原体16S rRNA基因,检测滴虫细胞内是否有人型支原体共生.对检出人型支原体DNA的分离株用32μg/ml多西环素清除支原体,比较清除前后甲硝唑MLC的变化.结果 160个阴道毛滴虫分离株中甲硝唑MLC为1~8μg/ml的占61.3%(98/160),16~32μg/ml的占26.3%(42/160),64~256μg/ml的占12.5%(20/160).PCR检测结果显示,有61株(38.1%)检出人型支原体DNA,其中MLC为1~8μg/ml的分离株检出率为13.3%(13/98),16~32μg/ml的分离株检出率为73.8%( 31/42),64~256μg/ml的分离株检出率为85.0%(17/20),不同MLC范围的分离株人型支原体检出率差异有统计学意义(P<0.01).用多西环素处理后,61株中仅有8株支原体被清除,清除前后甲硝唑MLC无明显变化.结论 四川地区的阴道毛滴虫分离株对甲硝唑表现出一定程度的耐药性,人型支原体的共生可能与之有关,但尚未发现直接证据.%Objective To investigate the relation of Mycoplasma hominis symbiosis and the resistence of Trichomonas vaginalit to metronidazole. Methods From November 2010 to July 2011, 160 isolates of T. Vaginalis were collected from the genital tract secretion of gynecological out-patients at the Sichuan Provincial Hospital for Women and Children. The minimum lethal concentration (MLC) to metronidazole of these isolates was determined by an in. Vitro sensitivity assay with different concentration gradients of metronidazole (from 1 to 1 024 μg/ml), and M

  10. Use of a lactic acid plus lactoserum intimate liquid soap for external hygiene in the prevention of bacterial vaginosis recurrence after metronidazole oral treatment Uso do ácido láctico com lactoserum em sabonete líquido íntimo para higiene externa na prevenção da recorrência de vaginose bacteriana após tratamento oral com metronidazol

    Directory of Open Access Journals (Sweden)

    M. Valeria Bahamondes

    2011-08-01

    Full Text Available OBJECTIVE: To determine the recurrence of bacterial vaginosis (BV after the use of a lactic acid plus lactoserum liquid soap starting immediately after the treatment with oral metronidazole and the quality of life of the participants. METHODS: A total of 123 women with diagnosis of BV with at least three of the following criteria: 1 homogeneous vaginal discharge without inflammation of the vagina or vulva; 2 vaginal pH ≥ 4.5; 3 positive Whiff test; and 4 "clue cells" in more than 20% of the epithelial cells in the vagina. A Nugent score ≥ 4 in the vaginal bacterioscopy was also used. After BV diagnosis, metronidazole 500 mg was administered orally bid during 7 days. Patients cured of BV were then instructed to use 7.5 to 10 mL of a lactic acid plus lactoserum liquid soap once-a-day for hygiene of the external genital region. Three subsequent control visits after starting the hygiene treatment (30, 60, and 90 days; ± 5 days were scheduled. A questionnaire was applied in the form of visual analogue scale (VAS in all the visits regarding: 1 level of comfort at the genital region; 2 malodorous external genitalia; 3 comfort in sexual intercourse; 4 satisfaction with intimate hygiene; and 5 self-esteem. RESULTS: Ninety two (74.8% women initiated the use of a lactic acid plus lactoserum liquid soap at visit 1. At visit 2, 3, and 4 there were 84, 62 and 42 women available for evaluation, respectively. The rate of recurrence of BV was 19.0%, 24.2% and 7.1%, respectively in the three visits and vaginal candidiasis was observed in five treated women. Quality of life was evaluated in the 42 women who completed the four visits schedule and there were significant improvement in the five domains assessed. CONCLUSION: A lactic acid plus lactoserum liquid soap for external intimate hygiene may be an option for the prevention of BV recurrence after treatment and cure with oral metronidazoleOBJETIVO: Determinar a ocorrência de vaginose bacteriana (VB após o

  11. Mice take calculated risks.

    Science.gov (United States)

    Kheifets, Aaron; Gallistel, C R

    2012-05-29

    Animals successfully navigate the world despite having only incomplete information about behaviorally important contingencies. It is an open question to what degree this behavior is driven by estimates of stochastic parameters (brain-constructed models of the experienced world) and to what degree it is directed by reinforcement-driven processes that optimize behavior in the limit without estimating stochastic parameters (model-free adaptation processes, such as associative learning). We find that mice adjust their behavior in response to a change in probability more quickly and abruptly than can be explained by differential reinforcement. Our results imply that mice represent probabilities and perform calculations over them to optimize their behavior, even when the optimization produces negligible material gain.

  12. Inborn anemias in mice

    International Nuclear Information System (INIS)

    Bernstein, S.E.; Barker, J.E.; Russell, E.S.

    1981-06-01

    hereditary anemias of mice have been the chief objects of investigation. At present under study are four macrocytic anemias, five hemolytic anemias, nonhemolytic microcytic anemia, transitory siderocytic anemia, sex-linked iron-transport anemia, an α-thalassemia, and a new target-cell anemia. Each of these blood dyscrasias is caused by the action of a unique mutant gene, which determines the structure of different intracellular molecules, and thus controls a different metabolic process. Thus our wide range of different hereditary anemias has considerable potential for uncovering many different aspects of hemopoietic homeostatic mechanisms in the mouse. Each anemia is studied through: (a) characterization of peripheral blood values, (b) determinations of radiosensitivity under a variety of conditions, (c) measurements of iron metabolism and heme synthesis, (d) histological and biochemical study of blood-forming tissue, (e) functional tests of the stem cell component, (f) examination of responses to erythroid stimuli, and (g) transplantation of tissue between individuals of differently affected genotypes

  13. Metronidazole removal in powder-activated carbon and concrete-containing graphene adsorption systems: Estimation of kinetic, equilibrium and thermodynamic parameters and optimization of adsorption by a central composite design.

    Science.gov (United States)

    Manjunath, S V; Kumar, S Mathava; Ngo, Huu Hao; Guo, Wenshan

    2017-12-06

    Metronidazole (MNZ) removal by two adsorbents, i.e., concrete-containing graphene (CG) and powder-activated carbon (PAC), was investigated via batch-mode experiments and the outcomes were used to analyze the kinetics, equilibrium and thermodynamics of MNZ adsorption. MNZ sorption on CG and PAC has followed the pseudo-second-order kinetic model, and the thermodynamic parameters revealed that MNZ adsorption was spontaneous on PAC and non-spontaneous on CG. Subsequently, two-parameter isotherm models, i.e., Langmuir, Freundlich, Temkin, Dubinin-Radushkevich and Elovich models, were applied to evaluate the MNZ adsorption capacity. The maximum MNZ adsorption capacities ([Formula: see text]) of PAC and CG were found to be between 25.5-32.8 mg/g and 0.41-0.002 mg/g, respectively. Subsequently, the effects of pH, temperature and adsorbent dosage on MNZ adsorption were evaluated by a central composite design (CCD) approach. The CCD experiments have pointed out the complete removal of MNZ at a much lower PAC dosage by increasing the system temperature (i.e., from 20°C to 40°C). On the other hand, a desorption experiment has shown 3.5% and 1.7% MNZ removal from the surface of PAC and CG, respectively, which was insignificant compared to the sorbed MNZ on the surface by adsorption. The overall findings indicate that PAC and CG with higher graphene content could be useful in MNZ removal from aqueous systems.

  14. Improvement Effect of Dewaxed Brown Rice on Constipation in Antibiotic-treated Mice.

    Science.gov (United States)

    Inagawa, Hiroyuki; Saika, Toshiyuki; Nishiyama, Naoki; Nisizawa, Takashi; Kohchi, Chie; Uenobe, Maya; Soma, Gen-Ichiro

    2017-01-01

    A decrease in gastrointestinal motility causing weakened lipopolysaccharide (LPS) - toll-like receptor (TLR)4 signaling along with a decline in the number of enteric bacteria is known to be a cause of constipation due to the administration of antibiotics. A new type of brown rice with its wax layer removed, resulting in quick-cooking and tasty product, contains 100-times more LPS than polished white rice. In this study, the improvement effect on constipation due to intake of dewaxed brown rice was examined. Dewaxed brown rice was prepared at Toyo Rice from brown rice. Mice were given powdered feed to which powdered rice containing 0-50% of dewaxed brown rice was added. Antibiotics were administered for 10 or 27 days in drinking water containing vancomycin, metronidazole and neomycin. LPS, used as a control, was freely provided in drinking water. The defecation frequency, stool weight per hour and body weight were determined on the last day. Although the 10-day administration of antibiotics reduced the stool weight per hour to half, the dewaxed brown rice and LPS groups showed a trend towards improvement at a level comparable to the group receiving no antibiotics. The body weight significantly decreased after the 27-day administration of antibiotics but was improved in the 50% dewaxed brown rice group at a level comparable to the group receiving no antibiotics. Though the defecation frequency and wet and dry stool weights per hour were reduced by as much as 50% in the group receiving antibiotics, a significant improvement in constipation was observed in the 50% dewaxed brown rice group. As the improvement effect of dewaxed brown rice on body weight loss and constipation caused by the long-term administration of antibiotics has been confirmed in animal experimentation, the introduction of dewaxed brown rice as a staple food to patients under long-term antibiotic treatment may improve constipation. Copyright© 2017, International Institute of Anticancer Research (Dr

  15. Effect of various antibiotics on modulation of intestinal microbiota and bile acid profile in mice

    International Nuclear Information System (INIS)

    Zhang, Youcai; Limaye, Pallavi B.; Renaud, Helen J.; Klaassen, Curtis D.

    2014-01-01

    Antibiotic treatments have been used to modulate intestinal bacteria and investigate the role of intestinal bacteria on bile acid (BA) homeostasis. However, knowledge on which intestinal bacteria and bile acids are modified by antibiotics is limited. In the present study, mice were administered various antibiotics, 47 of the most abundant bacterial species in intestine, as well as individual BAs in plasma, liver, and intestine were quantified. Compared to the two antibiotic combinations (vancomycin + imipenem and cephalothin + neomycin), the three single antibiotics (metronidazole, ciprofloxacin and aztreonam) have less effect on intestinal bacterial profiles, and thus on host BA profiles and mRNA expression of genes that are important for BA homeostasis. The two antibiotic combinations decreased the ratio of Firmicutes to Bacteroidetes in intestine, as well as most secondary BAs in serum, liver and intestine. Additionally, the two antibiotic combinations significantly increased mRNA of the hepatic BA uptake transporters (Ntcp and Oatp1b2) and canalicular BA efflux transporters (Bsep and Mrp2), but decreased mRNA of the hepatic BA synthetic enzyme Cyp8b1, suggesting an elevated enterohepatic circulation of BAs. Interestingly, the two antibiotic combinations tended to have opposite effect on the mRNAs of most intestinal genes, which tended to be inhibited by vancomycin + imipenem but stimulated by cephalothin + neomycin. To conclude, the present study clearly shows that various antibiotics have distinct effects on modulating intestinal bacteria and host BA metabolism. - Highlights: • Various antibiotics have different effects on intestinal bacteria. • Antibiotics alter bile acid composition in mouse liver and intestine. • Antibiotics influence genes involved in bile acid homeostasis. • Clostridia appear to be important for secondary bile acid formation

  16. Effect of various antibiotics on modulation of intestinal microbiota and bile acid profile in mice

    Energy Technology Data Exchange (ETDEWEB)

    Zhang, Youcai; Limaye, Pallavi B.; Renaud, Helen J.; Klaassen, Curtis D., E-mail: curtisklaassenphd@gmail.com

    2014-06-01

    Antibiotic treatments have been used to modulate intestinal bacteria and investigate the role of intestinal bacteria on bile acid (BA) homeostasis. However, knowledge on which intestinal bacteria and bile acids are modified by antibiotics is limited. In the present study, mice were administered various antibiotics, 47 of the most abundant bacterial species in intestine, as well as individual BAs in plasma, liver, and intestine were quantified. Compared to the two antibiotic combinations (vancomycin + imipenem and cephalothin + neomycin), the three single antibiotics (metronidazole, ciprofloxacin and aztreonam) have less effect on intestinal bacterial profiles, and thus on host BA profiles and mRNA expression of genes that are important for BA homeostasis. The two antibiotic combinations decreased the ratio of Firmicutes to Bacteroidetes in intestine, as well as most secondary BAs in serum, liver and intestine. Additionally, the two antibiotic combinations significantly increased mRNA of the hepatic BA uptake transporters (Ntcp and Oatp1b2) and canalicular BA efflux transporters (Bsep and Mrp2), but decreased mRNA of the hepatic BA synthetic enzyme Cyp8b1, suggesting an elevated enterohepatic circulation of BAs. Interestingly, the two antibiotic combinations tended to have opposite effect on the mRNAs of most intestinal genes, which tended to be inhibited by vancomycin + imipenem but stimulated by cephalothin + neomycin. To conclude, the present study clearly shows that various antibiotics have distinct effects on modulating intestinal bacteria and host BA metabolism. - Highlights: • Various antibiotics have different effects on intestinal bacteria. • Antibiotics alter bile acid composition in mouse liver and intestine. • Antibiotics influence genes involved in bile acid homeostasis. • Clostridia appear to be important for secondary bile acid formation.

  17. Improvement Effect of Dewaxed Brown Rice on Constipation in Antibiotic-treated Mice

    Science.gov (United States)

    INAGAWA, HIROYUKI; SAIKA, TOSHIYUKI; NISHIYAMA, NAOKI; NISIZAWA, TAKASHI; KOHCHI, CHIE; UENOBE, MAYA; SOMA, GEN-ICHIRO

    2017-01-01

    Background/Aim: A decrease in gastrointestinal motility causing weakened lipopolysaccharide (LPS) – toll-like receptor (TLR)4 signaling along with a decline in the number of enteric bacteria is known to be a cause of constipation due to the administration of antibiotics. A new type of brown rice with its wax layer removed, resulting in quick-cooking and tasty product, contains 100-times more LPS than polished white rice. In this study, the improvement effect on constipation due to intake of dewaxed brown rice was examined. Materials and Methods: Dewaxed brown rice was prepared at Toyo Rice from brown rice. Mice were given powdered feed to which powdered rice containing 0-50% of dewaxed brown rice was added. Antibiotics were administered for 10 or 27 days in drinking water containing vancomycin, metronidazole and neomycin. LPS, used as a control, was freely provided in drinking water. The defecation frequency, stool weight per hour and body weight were determined on the last day. Results: Although the 10-day administration of antibiotics reduced the stool weight per hour to half, the dewaxed brown rice and LPS groups showed a trend towards improvement at a level comparable to the group receiving no antibiotics. The body weight significantly decreased after the 27-day administration of antibiotics but was improved in the 50% dewaxed brown rice group at a level comparable to the group receiving no antibiotics. Though the defecation frequency and wet and dry stool weights per hour were reduced by as much as 50% in the group receiving antibiotics, a significant improvement in constipation was observed in the 50% dewaxed brown rice group. Conclusion: As the improvement effect of dewaxed brown rice on body weight loss and constipation caused by the long-term administration of antibiotics has been confirmed in animal experimentation, the introduction of dewaxed brown rice as a staple food to patients under long-term antibiotic treatment may improve constipation. PMID

  18. Resilience in Aging Mice.

    Science.gov (United States)

    Kirkland, James L; Stout, Michael B; Sierra, Felipe

    2016-11-01

    Recently discovered interventions that target fundamental aging mechanisms have been shown to increase life span in mice and other species, and in some cases, these same manipulations have been shown to enhance health span and alleviate multiple age-related diseases and conditions. Aging is generally associated with decreases in resilience, the capacity to respond to or recover from clinically relevant stresses such as surgery, infections, or vascular events. We hypothesize that the age-related increase in susceptibility to those diseases and conditions is driven by or associated with the decrease in resilience. Thus, a test for resilience at middle age or even earlier could represent a surrogate approach to test the hypothesis that an intervention delays the process of aging itself. For this, animal models to test resilience accurately and predictably are needed. In addition, interventions that increase resilience might lead to treatments aimed at enhancing recovery following acute illnesses, or preventing poor outcomes from medical interventions in older, prefrail subjects. At a meeting of basic researchers and clinicians engaged in research on mechanisms of aging and care of the elderly, the merits and drawbacks of investigating effects of interventions on resilience in mice were considered. Available and potential stressors for assessing physiological resilience as well as the notion of developing a limited battery of such stressors and how to rank them were discussed. Relevant ranking parameters included value in assessing general health (as opposed to focusing on a single physiological system), ease of use, cost, reproducibility, clinical relevance, and feasibility of being repeated in the same animal longitudinally. During the discussions it became clear that, while this is an important area, very little is known or established. Much more research is needed in the near future to develop appropriate tests of resilience in animal models within an aging context

  19. Testing of new hypoxic cell sensitizers in vivo

    International Nuclear Information System (INIS)

    Stone, H.B.; Sinesi, M.S.

    1982-01-01

    We tested five agents as potential sensitizers of hypoxic cells in vivo in mammary tumors in C3H mice in comparison with misonidazole. The LD/sub 50/2/ for desmethylmisonidazole was 2.7 mg/g body wt, compared to 1.3 for misonidazole. It was as effective in reducing the TCD 50 of MDAH-MCa-4 as were equitoxic doses of misonidazole. the LD/sub 50/2/ of SR-2508 was 3.3 mg/g and was as effective a sensitizer as misonidazole. Ro 07-0741 was more toxic, with an LD/sub 50/2/ of 0.6 mg/g, but was as effective as misonidazole at equitoxic doses. NP-1 was also more toxic than misonidazole (LA/sub 50/2/ = 04 mg/g) but was a less effective sensitizer. Rotenone, which causes sensitization by inhibiting cellular respiration, thus increasing the diffusion distance of oxygen, was extremely toxic (LD/sub 50/2/ - 0.003 mg/g), and systemic respiratory inhibition and the radioprotective effects of the dimethyl sulfoxide used to dissolve it rendered it totally ineffective as a sensitizer in vivo

  20. Mice, men and MHC supertypes

    DEFF Research Database (Denmark)

    Lundegaard, Claus

    2010-01-01

    vaccine formulations. Toxoplasma gondii, an intracellular parasite, causes severe neurologic and ocular disease in congenitally infected and immunocompromised individuals. No protective vaccine exists against human toxoplasmosis. However, studies with mice have revealed immunodominant cytotoxic T...

  1. 甲硝唑诱导阴道毛滴虫凋亡样细胞死亡%Induction of Apoptotic-like Cell Death in Trichomonas vaginalis by Metronidazole

    Institute of Scientific and Technical Information of China (English)

    邓致刚; 黄景政; 辛致炜; 张仁利; 刘居理; 傅玉才

    2007-01-01

    目的 凋亡或程序性细胞死亡在多细胞生物体中已经被广泛研究,然而,关于单细胞寄生性原生动物细胞凋亡发生的分子机制却知之甚少.本研究旨在了解甲硝唑诱导阴道毛滴虫细胞凋亡的特征.方法 培养阴道毛滴虫并用不同浓度的甲硝唑进行处理.在不同的时间间隔进行活细胞计数.提取甲硝唑处理过的阴道毛滴虫基因组进行DNA断裂片段检测.用DNA断端末端标记(TUNEL)法测定甲硝唑处理后阴道毛滴虫核酸内切酶活性.流式细胞检测分析脂酰丝氨酸暴露情况.结果 甲硝唑可以诱导阴道毛滴虫出现凋亡样细胞死亡.这种凋亡样细胞死亡表现为细胞皱缩,磷脂酰丝氨酸暴露以及核染色体凝聚,但并未检测到寡核苷酸DNA梯带.结论 阴道毛滴虫程序性细胞死亡的调节通路不同于多细胞生物体.确定导致原生动物细胞死亡的凋亡通路也许最终可用于鉴定新的治疗靶点.%Objective Apoptosis or programmed cell death(PCD) has been studied extensively in multicellular organisms,however,very little is known about the molecular mechanisms by which apoptosis occurs in unicellular protozoan parasites.The aim of this study is to characterize the apoptosis or PCD of Trichomonas vaginalis induced by metronidazole (MTZ).Methods T. Vaginalis strain cultures were treated with various concentrations of MTZ and the number of viable cells were determined at different time intervals.The genomic DNA of MTZ treated T. Vaginalis was extracted and DNA fragmentation was analyzed.TUNEL assay was carried out to detect the endonuclease activity in T. Vaginalis after MTZ treatment.Flow cytometric analysis was used to analyse the phosphatidylserine (PS) exposure of T. Vaginalis.Results Metronidazole (MTZ) induced an apoptotic-like cell death in T. Vaginalis.This apoptotic-like cell death was demonstrated by cell shrinkage,phosphatidylserine exposure,and nuclear chromatin condensation

  2. 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.

    Science.gov (United States)

    Rossi, Giacomo; Pengo, Graziano; Caldin, Marco; Palumbo Piccionello, Angela; Steiner, Jörg M; Cohen, Noah D; Jergens, Albert E; Suchodolski, Jan S

    2014-01-01

    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. 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 (Pdogs 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. 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 studies are warranted to evaluate the clinical efficacy of VSL#3 in canine IBD.

  3. Linkage disequilibrium in wild mice.

    Directory of Open Access Journals (Sweden)

    Cathy C Laurie

    2007-08-01

    Full Text Available Crosses between laboratory strains of mice provide a powerful way of detecting quantitative trait loci for complex traits related to human disease. Hundreds of these loci have been detected, but only a small number of the underlying causative genes have been identified. The main difficulty is the extensive linkage disequilibrium (LD in intercross progeny and the slow process of fine-scale mapping by traditional methods. Recently, new approaches have been introduced, such as association studies with inbred lines and multigenerational crosses. These approaches are very useful for interval reduction, but generally do not provide single-gene resolution because of strong LD extending over one to several megabases. Here, we investigate the genetic structure of a natural population of mice in Arizona to determine its suitability for fine-scale LD mapping and association studies. There are three main findings: (1 Arizona mice have a high level of genetic variation, which includes a large fraction of the sequence variation present in classical strains of laboratory mice; (2 they show clear evidence of local inbreeding but appear to lack stable population structure across the study area; and (3 LD decays with distance at a rate similar to human populations, which is considerably more rapid than in laboratory populations of mice. Strong associations in Arizona mice are limited primarily to markers less than 100 kb apart, which provides the possibility of fine-scale association mapping at the level of one or a few genes. Although other considerations, such as sample size requirements and marker discovery, are serious issues in the implementation of association studies, the genetic variation and LD results indicate that wild mice could provide a useful tool for identifying genes that cause variation in complex traits.

  4. Voluntary Wheel Running in Mice.

    Science.gov (United States)

    Goh, Jorming; Ladiges, Warren

    2015-12-02

    Voluntary wheel running in the mouse is used to assess physical performance and endurance and to model exercise training as a way to enhance health. Wheel running is a voluntary activity in contrast to other experimental exercise models in mice, which rely on aversive stimuli to force active movement. This protocol consists of allowing mice to run freely on the open surface of a slanted, plastic saucer-shaped wheel placed inside a standard mouse cage. Rotations are electronically transmitted to a USB hub so that frequency and rate of running can be captured via a software program for data storage and analysis for variable time periods. Mice are individually housed so that accurate recordings can be made for each animal. Factors such as mouse strain, gender, age, and individual motivation, which affect running activity, must be considered in the design of experiments using voluntary wheel running. Copyright © 2015 John Wiley & Sons, Inc.

  5. Radiation carcinogenesis in scid mice

    Energy Technology Data Exchange (ETDEWEB)

    Ishii, Hiroko; Nishimura, Mayumi; Kobayashi, Shigeru; Tsuji, Hideo; Shimada, Yoshiya; Ogiu, Toshiaki [National Inst. of Radiological Sciences, Chiba (Japan); Suzuki, Fumio; Sado, Toshihiko

    1999-06-01

    Scid mice which have the defect of DNA-dependent protein kinase catalitic subunit, exhibit the limited activities of repair from DNA double strand breaks, and are sensitive to ionizing radiation. In order to study the relationship between repair capacity for DNA double strand breaks and carcinogenesis, the effects of ionizing radiation were studied using scid homozygotes (scid/scid), scid heterozygotes (scid/+) and CB-17 (+/+) mice. Both the Scid bone marrow cells and fibroblast cell lines from Scid embryos were highly sensitivity to acute effects of ionizing radiation. Carcinogenesis experiments showed the high incidence of thymic lymphomas (80 to 90%) in 1 to 3 Gy {sup 137}Cs-{gamma}-ray-irradiated Scid mice. (author)

  6. Real-time Tumor Oxygenation Changes After Single High-dose Radiation Therapy in Orthotopic and Subcutaneous Lung Cancer in Mice: Clinical Implication for Stereotactic Ablative Radiation Therapy Schedule Optimization

    Energy Technology Data Exchange (ETDEWEB)

    Song, Changhoon [Department of Radiation Oncology, Seoul National University College of Medicine, Seoul (Korea, Republic of); Hong, Beom-Ju; Bok, Seoyeon; Lee, Chan-Ju; Kim, Young-Eun [Division of Integrative Biosciences and Biotechnology, Pohang University of Science and Technology, Pohang, Gyeongbuk (Korea, Republic of); Jeon, Sang-Rok [Department of Radiation Oncology, Seoul National University College of Medicine, Seoul (Korea, Republic of); Cancer Research Institute, Seoul National University College of Medicine, Seoul (Korea, Republic of); Wu, Hong-Gyun [Department of Radiation Oncology, Seoul National University College of Medicine, Seoul (Korea, Republic of); Cancer Research Institute, Seoul National University College of Medicine, Seoul (Korea, Republic of); Institute of Radiation Medicine, Medical Research Center, Seoul National University College of Medicine, Seoul (Korea, Republic of); Lee, Yun-Sang [Department of Nuclear Medicine, Seoul National University College of Medicine, Seoul (Korea, Republic of); Department of Molecular Medicine and Biopharmaceutical Sciences, Seoul National University College of Medicine, Seoul (Korea, Republic of); Cheon, Gi Jeong; Paeng, Jin Chul [Cancer Research Institute, Seoul National University College of Medicine, Seoul (Korea, Republic of); Institute of Radiation Medicine, Medical Research Center, Seoul National University College of Medicine, Seoul (Korea, Republic of); Department of Nuclear Medicine, Seoul National University College of Medicine, Seoul (Korea, Republic of); Carlson, David J. [Department of Therapeutic Radiology, Yale University School of Medicine, New Haven, Connecticut (United States); and others

    2016-07-01

    Purpose: To investigate the serial changes of tumor hypoxia in response to single high-dose irradiation by various clinical and preclinical methods to propose an optimal fractionation schedule for stereotactic ablative radiation therapy. Methods and Materials: Syngeneic Lewis lung carcinomas were grown either orthotopically or subcutaneously in C57BL/6 mice and irradiated with a single dose of 15 Gy to mimic stereotactic ablative radiation therapy used in the clinic. Serial [{sup 18}F]-misonidazole (F-MISO) positron emission tomography (PET) imaging, pimonidazole fluorescence-activated cell sorting analyses, hypoxia-responsive element-driven bioluminescence, and Hoechst 33342 perfusion were performed before irradiation (day −1), at 6 hours (day 0), and 2 (day 2) and 6 (day 6) days after irradiation for both subcutaneous and orthotopic lung tumors. For F-MISO, the tumor/brain ratio was analyzed. Results: Hypoxic signals were too low to quantitate for orthotopic tumors using F-MISO PET or hypoxia-responsive element-driven bioluminescence imaging. In subcutaneous tumors, the maximum tumor/brain ratio was 2.87 ± 0.483 at day −1, 1.67 ± 0.116 at day 0, 2.92 ± 0.334 at day 2, and 2.13 ± 0.385 at day 6, indicating that tumor hypoxia was decreased immediately after irradiation and had returned to the pretreatment levels at day 2, followed by a slight decrease by day 6 after radiation. Pimonidazole analysis also revealed similar patterns. Using Hoechst 33342 vascular perfusion dye, CD31, and cleaved caspase 3 co-immunostaining, we found a rapid and transient vascular collapse, which might have resulted in poor intratumor perfusion of F-MISO PET tracer or pimonidazole delivered at day 0, leading to decreased hypoxic signals at day 0 by PET or pimonidazole analyses. Conclusions: We found tumor hypoxia levels decreased immediately after delivery of a single dose of 15 Gy and had returned to the pretreatment levels 2 days after irradiation and had decreased

  7. Modified Protein Improves Vitiligo Symptoms in Mice

    Science.gov (United States)

    ... Vitiligo Symptoms in Mice Spotlight on Research Modified Protein Improves Vitiligo Symptoms in Mice By Colleen Labbe, ... D., Ph.D., Rush University. Altering a key protein involved in the development of vitiligo may protect ...

  8. Immunobiology of congenitally athymic-asplenic mice

    International Nuclear Information System (INIS)

    Gershwin, M.E.; Ahmed, A.; Ikeda, R.M.; Shifrine, M.; Wilson, F.

    1978-01-01

    A study has been made of congenitally athymic-asplenic mice obtained by the mating of nude by hereditarily asplenic (Dh/+) mice. The mice survived for up to 9 months, under specific pathogen-free conditions, with no evidence for increased risk of spontaneous neoplasia. Although lymphocyte surface markers and sera immunoglobulin levels of athymic-asplenic mice were similar to those of their nude and asplenic littermates, there were a number of major immunologic differences. The athymic-asplenic mice appeared more immunologically compromised than nude mice. There was an elevated rate of growth and a lower inoculated cell threshold needed for successful transplantation of a human malignant melanoma. There was no evidence for auto-antibody production in mice up to 9 months of age. Congenitally athymic-asplenic mice can be used for a variety of studies in which other immunologically deprived mouse mutants are desired. (author)

  9. Cassava is not a goitrogen in mice

    International Nuclear Information System (INIS)

    Hershman, J.M.; Pekary, A.E.; Sugawara, M.; Adler, M.; Turner, L.; Demetriou, J.A.; Hershman, J.D.

    1985-01-01

    To examine the effect of cassava on the thyroid function of mice, the authors fed fresh cassava root to mice and compared this diet with low iodine diet and Purina. Cassava provided a low iodine intake and increased urine thiocyanate excretion and serum thiocyanate levels. Mice on cassava lost weight. The thyroid glands of mice on cassava were not enlarged, even when normalized for body weight. The 4- and 24-hr thyroid uptakes of mice on cassava were similar to those of mice on low iodine diets. Protein-bound [ 125 I]iodine at 24 hr was high in mice on either the cassava or low iodine diets. The thyroid iodide trap (T/M) was similar in mice on cassava and low iodine diets. When thiocyanate was added in vitro to the incubation medium, T/M was reduced in all groups of mice; under these conditions, thiocyanate caused a dose-related inhibition of T/M. The serum thyroxine (T4) and triiodothyronine (T3) concentrations of mice on cassava were reduced compared with mice on Purina diet. Thyroid T4 and T3 contents of mice on cassava were relatively low compared with mice on Purina diet. Hepatic T3 content and T4 5'-monodeiodination in liver homogenates were reduced in mice on cassava compared with other groups. The data show that cassava does not cause goiter in mice. The thiocyanate formed from ingestation of cassava is insufficient to inhibit thyroid iodide transport or organification of iodide. The cassava diet leads to rapid turnover of hormonal iodine because it is a low iodine diet. It also impairs 5'-monodeiodination of T4 which may be related to nutritional deficiency. These data in mice do not support the concept that cassava per se has goitrogenic action in man

  10. Compensatory eye movements in mice

    NARCIS (Netherlands)

    A.M. van Alphen (Arjan)

    2002-01-01

    textabstractThis thesis will address the generation of compensatory eye movements in naturally mutated or genetically modified mice. The reason for generating compensatory eye movements is solely related to the requirements for good vision. In a subject moving through its environment the projection

  11. Transplacental arsenic carcinogenesis in mice

    International Nuclear Information System (INIS)

    Waalkes, Michael P.; Liu, Jie; Diwan, Bhalchandra A.

    2007-01-01

    Our work has focused on the carcinogenic effects of in utero arsenic exposure in mice. Our data show that a short period of maternal exposure to inorganic arsenic in the drinking water is an effective, multi-tissue carcinogen in the adult offspring. These studies have been reproduced in three temporally separate studies using two different mouse strains. In these studies pregnant mice were treated with drinking water containing sodium arsenite at up to 85 ppm arsenic from days 8 to 18 of gestation, and the offspring were observed for up to 2 years. The doses used in all these studies were well tolerated by both the dam and offspring. In C3H mice, two separate studies show male offspring exposed to arsenic in utero developed liver carcinoma and adrenal cortical adenoma in a dose-related fashion during adulthood. Prenatally exposed female C3H offspring show dose-related increases in ovarian tumors and lung carcinoma and in proliferative lesions (tumors plus preneoplastic hyperplasia) of the uterus and oviduct. In addition, prenatal arsenic plus postnatal exposure to the tumor promoter, 12-O-tetradecanoyl phorbol-13-acetate (TPA) in C3H mice produces excess lung tumors in both sexes and liver tumors in females. Male CD1 mice treated with arsenic in utero develop tumors of the liver and adrenal and renal hyperplasia while females develop tumors of urogenital system, ovary, uterus and adrenal and hyperplasia of the oviduct. Additional postnatal treatment with diethylstilbestrol or tamoxifen after prenatal arsenic in CD1 mice induces urinary bladder transitional cell proliferative lesions, including carcinoma and papilloma, and enhances the carcinogenic response in the liver of both sexes. Overall this model has provided convincing evidence that arsenic is a transplacental carcinogen in mice with the ability to target tissues of potential human relevance, such as the urinary bladder, lung and liver. Transplacental carcinogenesis clearly occurs with other agents in humans

  12. Liquid chromatography–tandem mass spectrometry for the simultaneous quantitation of ceftriaxone, metronidazole and hydroxymetronidazole in plasma from seriously ill, severely malnourished children [version 2; referees: 1 approved, 3 approved with reservations

    Directory of Open Access Journals (Sweden)

    Martin Ongas

    2018-01-01

    Full Text Available We have developed and validated a novel, sensitive, selective and reproducible reversed-phase high-performance liquid chromatography method coupled with electrospray ionization mass spectrometry (HPLC–ESI-MS/MS for the simultaneous quantitation of ceftriaxone (CEF, metronidazole (MET and hydroxymetronidazole (MET-OH from only 50 µL of human plasma, and unbound CEF from 25 µL plasma ultra-filtrate to evaluate the effect of protein binding. Cefuroxime axetil (CEFU was used as an internal standard (IS. The analytes were extracted by a protein precipitation procedure with acetonitrile and separated on a reversed-phase Polaris 5 C18-Analytical column using a mobile phase composed of acetonitrile containing 0.1% (v/v formic acid and 10 mM aqueous ammonium formate pH 2.5, delivered at a flow-rate of 300 µL/min. Multiple reaction monitoring was performed in the positive ion mode using the transitions m/z555.1→m/z396.0 (CEF, m/z172.2→m/z 128.2 (MET, m/z188.0→m/z125.9 (MET-OH and m/z528.1→m/z 364.0 (CEFU to quantify the drugs. Calibration curves in spiked plasma and ultra-filtrate were linear (r2 ≥ 0.9948 from 0.4–300 µg/mL for CEF, 0.05–50 µg/mL for MET and 0.02 – 30 µg/mL for MET-OH. The intra- and inter- assay precisions were less than 9% and the mean extraction recoveries were 94.0% (CEF, 98.2% (MET, 99.6% (MET-OH and 104.6% (CEF in ultra-filtrate; the recoveries for the IS were 93.8% (in plasma and 97.6% (in ultra-filtrate. The validated method was successfully applied to a pharmacokinetic study of CEF, MET and MET-OH in hospitalized children with complicated severe acute malnutrition following an oral administration of MET and intravenous administration of CEF over the course of 72 hours.

  13. 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.

    Directory of Open Access Journals (Sweden)

    Giacomo Rossi

    Full Text Available 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

  14. Cardiac dysfunction in pneumovirus-induced lung injury in mice

    NARCIS (Netherlands)

    Bem, Reinout A.; van den Berg, Elske; Suidgeest, Ernst; van der Weerd, Louise; van Woensel, Job B. M.; Grotenhuis, Heynric B.

    2013-01-01

    To determine biventricular cardiac function in pneumovirus-induced acute lung injury in spontaneously breathing mice. Experimental animal study. Animal laboratory. C57Bl/6 mice. Mice were inoculated with the rodent pneumovirus, pneumonia virus of mice. Pneumonia virus of mice-infected mice were

  15. Preparation of hypoxic imaging agents 99Tcm-MNLS and 99Tcm-MLS and their biodistribution in mice

    International Nuclear Information System (INIS)

    Zha Zhihao; Wang Jianjun; Zhu Lin

    2009-01-01

    To develop 99 Tc m labeled hypoxic agents,two phosphate-based chelating agents were coupled to metronidazole, 2- (2-methyl-5-nitro-1H-imidazol-1-yl) ethyl dihydrogen phosphate (MNLS) and its analog 2- (2-methyl-1H-imidazol-1-yl) ethyl dihydrogen phosphate (MLS) were synthesized based on the mechanism of prodrug. Labeling yield of these 99 Tc m complexes were more than 90% as proved by TLC. Paper electrophoresis showed that these complexes were neutral. Biodistribution of these complexes in tumor-bearing mice showed that the uptake of 99 Tc m -MNLS (120 min, 2.99 ± 0.25 ID%/g) in tumor was higher than that of 99 Tc m -HL91 (120 min, 0.93 ± 0.13 ID%/g) and 99 Tc m -MLS (120 min, 1.61 ± 0.13 ID%/g), and the uptake ratio of tumor to muscle and tumor to liver of 99 Tc m -MNLS (120 min, 5.90, 1.03) were higher than that of 99 Tc m -HL91 (120 min, 3.59, 0.17) and 99 Tc m -MLS (120 min, 5.40, 0.13). The higher tumor uptake for 99 Tc m -MNLS than 99 Tc m -MLS suggested that nitroimidazole was a key group for tumor accumulation. 99 Tc m -MNLS had higher tumor uptake and lower liver uptake, which had the potential for tumor imaging and was worth of further vestigation. (authors)

  16. Experimental study on the sensitivity of isolated strains of trichomonas vaginalis in Shiyan city to metronidazole%阴道毛滴虫十堰分离株对灭滴灵敏感性的实验研究

    Institute of Scientific and Technical Information of China (English)

    杨树国; 王娅; 张光玉; 杨宏伟

    2011-01-01

    目的:实验观察阴道毛滴虫十堰分离株对灭滴灵的敏感性.方法:收集阴道毛滴虫临床分离株,体外传代培养4代,培养11管至对数生长期,调整虫体浓度为0.5×10 6个/ml,计算加入甲硝唑,使终浓度分别为:62.50 μg/ml、50.00 μg/ml、31.25 μg/ml、25.00 μg/ml、15.63 μg/ml、7.81 μg/ml、3.91 μg/ml、1.95 μg/ml、0.98 μg/ml、0.49 μg/ml、0 μg/ml,置37℃培养,分别于2、4、6、8、12、24 h观察虫体生长存活情况,计算高倍镜下虫体数目和死亡率.结果:62.50 μg/ml和50.00 μg/ml浓度组,滴虫死亡率均为100.00%;作用后2 h,15.63 μg/ml浓度组死亡率为7.69%,31.25 μg/ml组死亡率为65.51%;作用后4 h,7.81 μg/ml浓度组死亡率为78.94%,3.91 μg/ml浓度组死亡率为18.75%;作用后6 h,3.91 μg/ml浓度组死亡率为73.68%,1.95 μg/ml浓度组死亡率为21.52%;24 h滴虫最低致死量为3.91 μg/ml.结论:阴道毛滴虫十堰分离株对灭滴灵较敏感,体外有效最低杀虫浓度为3.91 μg/ml.%Objective: To observe the sensitivity of isolated strains of trichomonas vagina lis in Shiyan city to metronidazole. Methods: The clinical isolated strains of trichomonas vaginalis were collected, cultured for four generations in vitro, the clinical isolated strains in 11 tubes were cultivated to exponential phase, then the concentration of trichomonas vaginalis was regulated at 0.5 × 106/ml, metronidazole was added into the tubes, the terminal concentrations were 62.50 μg/ml, 50. 00 μg/ml, 31.25 μg/ml,25.00 μg/ml, 15.63 μg/ml, 7. 81 μg/ml, 3.91 μg/ml, 1.95 μg/ml, 0. 98 μg/ml, 0. 49 μg/ml and 0 μg/ml, the clinical isolated strains of trichomonas vaginalis were cultivated at 37℃, then the survival conditions of trichomonas vaginalis were observed at 2, 4, 6, 8, 12 and 24 hours; the amount and death rates of trichomonas vaginalis were calculated under high power lens. Results: 62. 50 μg/ml group and 50. 00 μg/ml group: the death rates of trichomonas

  17. MAUS: MICE Analysis User Software

    CERN Multimedia

    CERN. Geneva

    2012-01-01

    The Muon Ionization Cooling Experiment (MICE) has developed the MICE Analysis User Software (MAUS) to simulate and analyse experimental data. It serves as the primary codebase for the experiment, providing for online data quality checks and offline batch simulation and reconstruction. The code is structured in a Map-Reduce framework to allow parallelization whether on a personal machine or in the control room. Various software engineering practices from industry are also used to ensure correct and maintainable physics code, which include unit, functional and integration tests, continuous integration and load testing, code reviews, and distributed version control systems. Lastly, there are various small design decisions like using JSON as the data structure, using SWIG to allow developers to write components in either Python or C++, or using the SCons python-based build system that may be of interest to other experiments.

  18. Progress of MICE RFCC Module

    Energy Technology Data Exchange (ETDEWEB)

    Li, D.; Bowring, D.; DeMello, A.; Gourlay, S.; Green, M.; Li, N.; Niinikoski, T.; Pan, H.; Prestemon, S.; Virostek, S.; Zisman, M.; Bross, A.; Carcagno, R.; Kashikhin, V.; Sylvester, C.; Chen, A. B.; Guo, Bin; Li, Liyi; Xu, Fengyu; Cao, Y.; Sun, S.; Wang, Li; Yin, Lixin; Luo, Tianhuan; Summers, Don; Smith, B.; Radovinsky, A.; Zhukovsky, A.; Kaplan, D.

    2012-05-20

    Recent progress on the design and fabrication of the RFCC (RF and superconducting Coupling Coil) module for the international MICE (Muon Ionization Cooling Experiment) are reported. The MICE ionization cooling channel has two RFCC modules, each having four 201- MHz normal conducting RF cavities surrounded by one superconducting coupling coil (solenoid) magnet. The magnet is designed to be cooled by three cryocoolers. Fabrication of the RF cavities is complete; preparation for the cavity electro-polishing, low power RF measurements, and tuning are in progress at Lawrence Berkeley National Laboratory (LBNL). Fabrication of the cold mass of the first coupling coil magnet has been completed in China and the cold mass arrived at LBNL in late 2011. Preparations for testing the cold mass are currently under way at Fermilab. Plans for the RFCC module assembly and integration are being developed and are described.

  19. Protein malnutrition and metronidazole induced intestinal bacterial ...

    African Journals Online (AJOL)

    STORAGESEVER

    2008-09-17

    Sep 17, 2008 ... Figure 1. Weight loss in different situation of diets. Each point represents ... using sterile ground-glass stoppers (Heimo et al., 2001). To .... In fact, selective elimination ... attention in recent years, because the ability of bacteria.

  20. Protein malnutrition and metronidazole induced intestinal bacterial ...

    African Journals Online (AJOL)

    This study was designed to assess the effects of protein malnutrition (PM) associated with antibiotic on growth weight, cecal bacterial overgrowth and enterobacteria translocation. Eighteen Gnotobiotic young Wistar rats (135 ± 2.35 g) were treated orally with antibiotic and submitted to dietary restriction based on maize diet ...

  1. Therapeutic cloning in individual parkinsonian mice

    Science.gov (United States)

    Tabar, Viviane; Tomishima, Mark; Panagiotakos, Georgia; Wakayama, Sayaka; Menon, Jayanthi; Chan, Bill; Mizutani, Eiji; Al-Shamy, George; Ohta, Hiroshi; Wakayama, Teruhiko; Studer, Lorenz

    2009-01-01

    Cell transplantation with embryonic stem (ES) cell progeny requires immunological compatibility with host tissue. ‘Therapeutic cloning’ is a strategy to overcome this limitation by generating nuclear transfer (nt)ES cells that are genetically matched to an individual. Here we establish the feasibility of treating individual mice via therapeutic cloning. Derivation of 187 ntES cell lines from 24 parkinsonian mice, dopaminergic differentiation, and transplantation into individually matched host mice showed therapeutic efficacy and lack of immunological response. PMID:18376409

  2. Transplantation of canine osteosarcoma into nude mice

    International Nuclear Information System (INIS)

    Shifrine, M.; Taylor, N.; Holloway, G.; Arnstein, P.R.; Chrisp, C.; Pool, R.; Whaley, C.

    1975-01-01

    Osteosarcomas from dogs were inoculated subcutaneously into mice. Sixty days later six mice had tumors that gradually increased in size. All tumors were undifferentiated sarcomas. Karyotypes of osteosarcomas grown in tissue culture and of tumors from mice inoculated with the culture were similar with two marker chromosomes. It was thus shown that radioinduced osteosarcomas can be cultivated in tissue culture while retaining their marker chromosomes and malignancy

  3. Zinc metabolism in genetically obese mice

    International Nuclear Information System (INIS)

    Kennedy, M.L.; Failla, M.L.

    1986-01-01

    Recent reports indicate that the concentrations and total amounts of several essential trace metals in various tissues of genetically obese rodents differ markedly from lean controls. In the present studies the absorption, retention and tissue distribution of zinc was compared in obese (ob/ob) and lean (+/?) C57BL/6J mice. When administered 0.1 and 1 umole 65 Zn by stomach tube and killed after 4 h, fasted 10 week old obese mice had 2.7 and 2.2 times more radioactivity in their carcasses, respectively, than age-matched lean mice. Higher levels of 65 Zn were also present in the intestinal mucosa of obese mice. To eliminate possible differences in the effects of fasting and gastric emptying rates between the phenotypes, zinc absorption and retention were determined according to the method of Heth and Hoekstra. Analysis of data revealed that obese and lean mice absorbed 43 and 18% of the oral dose, respectively. Also, the rate of 65 Zn excretion between 2 and 6 days post-treatment was similar for obese and lean mice. After 6 days obese mice had significantly lower levels of radioisotope in skin, muscle plus bone, spleen and testes and higher levels of 65 Zn in liver, small intestine and adipose tissue compared to tissues from lean mice. These results demonstrate increased absorption, altered tissue distribution and similar excretion of zinc in ob/ob mice

  4. Testosterone and Dihydrotestosterone Differentially Improve Cognition in Aged Female Mice

    Science.gov (United States)

    Benice, Ted S.; Raber, Jacob

    2009-01-01

    Compared with age-matched male mice, female mice experience a more severe age-related cognitive decline (ACD). Since androgens are less abundant in aged female mice compared with aged male mice, androgen supplementation may enhance cognition in aged female mice. To test this, we assessed behavioral performance on a variety of tasks in 22- to…

  5. Radiosensitization, mutagenicity, and toxicity of Escherichia coli by several nitrofurans and nitroimidazoles. [X radiation

    Energy Technology Data Exchange (ETDEWEB)

    Chessin, H.; McLaughlin, T.; Mroczkowski, Z.; Rupp, W.D.; Low, K.B.

    1978-08-01

    Representative nitrofurans (nitrofurantoin, nifuroxime, NF-167, NF-269) and nitroimidazoles (metronidazole, misonidazole) were found to sensitize hypoxic RecA/sup -/ Escherichia coli cells to X irradiation. These compounds were also mutagenic to E. coli using a UvrA/sup -/ strain as a test system, and toxic at high concentrations, using several strains differing in their repair capacity. However, the relative degrees of radiosensitization, mutagenicity, and toxicity, for the various compounds, were not simply correlated, suggesting that potential radiosensitizers with fewer side effects could be screened using bacteria.

  6. Double-stranded RNA viral infection of Trichomonas vaginalis isolates and its effect on the metronidazole resistance of parasites%阴道毛滴虫双链RNA病毒感染及其对甲硝唑耐药性的影响

    Institute of Scientific and Technical Information of China (English)

    王丽娟; 王东; 袁玉青; 杜纪英; 薛长责

    2011-01-01

    Objective To investigate Trichomonas vaginalis isolates from Henan Province for the presence of T. vagi-nalis virus(TVV) and analyze the effect of TVV of the metronidazole resistance of T. vaginalis. Methods DNA and RNA were simultaneously extracted after T. vaginalis isolates were grown on TYM (trypticase-yeast extract-maltose) medium and maintained as axenic cultures. Samples were then analyzed on 1 % agarose gel. The MLC of metronidazole of T. vaginalis isolates was tested using serial dilution. Results TVV was detected in 6 of 30 T. vaginalis isolates; the rate of TVV infection in T. vaginalis isolates was 20. 0%. The MLC of metronidazole against TVV-negative T. vaginalis strains in vitro was (24. 27 ±20. 899)μg/ml. This was significantly higher than that against TVV-positive strains (5. 68±3. 588)μg/ml), and the difference between the two was statistically significant(t = 2. 143,P<0. 05). Conclusion T. vaginalis virus was detected in T. vaginalis isolates from Henan. T. vaginalis isolates not harboring TVV were more likely to be resistant to metronidazole.%目的 调查河南地区阴道毛滴虫临床分离株阴道毛滴虫病毒感染情况,探索病毒感染对阴道毛滴虫甲硝唑耐药性的影响.方法 TYM(trypticase-yeast extract-maltose)无菌培养基培养阴道毛滴虫临床分离株,达到纯培养后提取虫体总核酸(DNA和RNA),进行1%琼脂糖凝胶电泳分析;连续稀释法测量每株虫体的甲硝唑最小致死浓度.结果 对30株阴道毛滴虫总核酸进行电泳,其中6株有5.5 kb双链RNA病毒带,病毒感染率为20.0%.阴道毛滴虫病毒阴性组甲硝唑最小致死浓度为( 24.27±20.899)μg/ml,病毒阳性组为(5.68±3.588)μg/ml,差异有统计学意义(t=2.143,P<0.05).结论 河南地区阴道毛滴虫临床分离株中检测到阴道毛滴虫病毒,无阴道毛滴虫病毒寄生的虫体易发生甲硝唑抵抗.

  7. Postnatal hematopoiesis and gut microbiota in NOD mice deviate from C57BL/6 mice

    DEFF Research Database (Denmark)

    Damlund, Dina Silke Malling; Metzdorff, Stine Broeng; Hasselby, Jane Preuss

    2016-01-01

    , a distinct splenic cell profile high in a granulocytic phenotype was evident in the neonatal NOD mice whereas neonatal C57BL/6 mice showed a profile rich in monocytes. Neonatal expression of Reg3g and Muc2 in the gut was deviating in NOD mice and coincided with fewer bacteria attaching to the Mucosal surface...

  8. Probabilistic numerical discrimination in mice.

    Science.gov (United States)

    Berkay, Dilara; Çavdaroğlu, Bilgehan; Balcı, Fuat

    2016-03-01

    Previous studies showed that both human and non-human animals can discriminate between different quantities (i.e., time intervals, numerosities) with a limited level of precision due to their endogenous/representational uncertainty. In addition, other studies have shown that subjects can modulate their temporal categorization responses adaptively by incorporating information gathered regarding probabilistic contingencies into their time-based decisions. Despite the psychophysical similarities between the interval timing and nonverbal counting functions, the sensitivity of count-based decisions to probabilistic information remains an unanswered question. In the current study, we investigated whether exogenous probabilistic information can be integrated into numerosity-based judgments by mice. In the task employed in this study, reward was presented either after few (i.e., 10) or many (i.e., 20) lever presses, the last of which had to be emitted on the lever associated with the corresponding trial type. In order to investigate the effect of probabilistic information on performance in this task, we manipulated the relative frequency of different trial types across different experimental conditions. We evaluated the behavioral performance of the animals under models that differed in terms of their assumptions regarding the cost of responding (e.g., logarithmically increasing vs. no response cost). Our results showed for the first time that mice could adaptively modulate their count-based decisions based on the experienced probabilistic contingencies in directions predicted by optimality.

  9. AGONISTIC BEHAVIOR OF LABORATORY MICE

    Directory of Open Access Journals (Sweden)

    D. Cinghiţă

    2005-01-01

    Full Text Available In this work we study agonistic behavior of laboratory white mice when they are kept in captivity. For all this experimental work we used direct observation of mice, in small lists, because we need a reduced space to emphasize characteristics of agonistic behavior. Relations between members of the same species that live in organized groups are based in most cases on hierarchical structure. Relations between leader and subservient, decided by fighting, involve a thorough observation between individuals. Each member of a group has its own place on the ierarchical scale depending on resultes of fhights – it can be leader or it can be subsurvient, depending on if it wines or looses the fight. Once hierarchical scale made, every animal will adjust its behavior. After analyzing the obtained data we have enough reasons to believe that after fights the winner, usually, is the massive mouse, but it is also very important the sexual ripeness, so the immature male will be beaten. The leader male had a big exploring area and it checks up all territory.The females can be more aggressive, its fights are more brutal, than male fights are, when they fight for supremacy, but in this case fights are not as frequent as in the case of males. Always the superior female, on hierarchical scale, shows males its own statute, so the strongest genes will be perpetuated.

  10. Mice embryology: a microscopic overview.

    Science.gov (United States)

    Salvadori, Maria Letícia Baptista; Lessa, Thais Borges; Russo, Fabiele Baldino; Fernandes, Renata Avancini; Kfoury, José Roberto; Braga, Patricia Cristina Baleeiro Beltrão; Miglino, Maria Angélica

    2012-10-01

    In this work, we studied the embryology of mice of 12, 14, and 18 days of gestation by gross observation, light microscopy, and scanning electron microscopy. Grossly, the embryos of 12 days were observed in C-shaped region of the brain, eye pigmentation of the retina, first, second, and third pharyngeal arches gill pit nasal region on the fourth ventricle brain, cervical curvature, heart, liver, limb bud thoracic, spinal cord, tail, umbilical cord, and place of the mesonephric ridge. Microscopically, the liver, cardiovascular system and spinal cord were observed. In the embryo of 14 days, we observed structures that make up the liver and heart. At 18 days of gestation fetuses, it was noted the presence of eyes, mouth, and nose in the cephalic region, chest and pelvic region with the presence of well-developed limbs, umbilical cord, and placenta. Scanning electron microscopy in 18 days of gestation fetuses evidenced head, eyes closed eyelids, nose, vibrissae, forelimb, heart, lung, kidney, liver, small bowel, diaphragm, and part of the spine. The results obtained in this work describe the internal and external morphology of mice, provided by an integration of techniques and review of the morphological knowledge of the embryonic development of this species, as this animal is of great importance to scientific studies. Copyright © 2012 Wiley Periodicals, Inc.

  11. Euthanasia of neonatal mice with carbon dioxide

    Science.gov (United States)

    Pritchett, K.; Corrow, D.; Stockwell, J.; Smith, A.

    2005-01-01

    Exposure to carbon dioxide (CO2) is the most prevalent method used to euthanize rodents in biomedical research. The purpose of this study was to determine the time of CO2 exposure required to euthanize neonatal mice (0 to 10 days old). Multiple groups of mice were exposed to 100% CO 2 for time periods between 5 and 60 min. Mice were placed in room air for 10 or 20 min after CO2 exposure, to allow for the chance of recovery. If mice recovered at one time point, a longer exposure was examined. Inbred and outbred mice were compared. Results of the study indicated that time to death varied with the age of the animals and could be as long as 50 min on the day of birth and differed between inbred and outbred mice. Institutions euthanizing neonatal mice with CO2 may wish to adjust their CO 2 exposure time periods according the age of the mice and their genetic background. Copyright 2005 by the American Association for Laboratory Animal Science.

  12. Reduced alcohol consumption in mice lacking preprodynorphin.

    Science.gov (United States)

    Blednov, Yuri A; Walker, Danielle; Martinez, Marni; Harris, R Adron

    2006-10-01

    Many studies suggest a role for endogenous opioid peptides and their receptors in regulation of ethanol intake. It is commonly accepted that the kappa-opioid receptors and their endogenous ligands, dynorphins, produce a dysphoric state and therefore may be responsible for avoidance of alcohol. We used mutant mice lacking preprodynorphin in a variety of behavioral tests of alcohol actions. Null mutant female, but not male, mice showed significantly lower preference for alcohol and consumed lower amounts of alcohol in a two-bottle choice test as compared with wild-type littermates. In the same test, knockout mice of both sexes showed a strong reduction of preference for saccharin compared to control mice. In contrast, under conditions of limited (4 h) access (light phase of the light/dark cycle), null mutant mice did not show any differences in consumption of saccharin, but they showed significantly reduced intake of sucrose. To determine the possible cause for reduction of ethanol preference and intake, we studied other ethanol-related behaviors in mice lacking the preprodynorphin gene. There were no differences between null mutant and wild-type mice in ethanol-induced loss of righting reflex, acute ethanol withdrawal, ethanol-induced conditioned place preference, or conditioned taste aversion to ethanol. These results indicate that deletion of preprodynorphin leads to substantial reduction of alcohol intake in female mice, and suggest that this is caused by decreased orosensory reward of alcohol (sweet taste and/or palatability).

  13. Collagen-induced arthritis in mice

    NARCIS (Netherlands)

    Bevaart, Lisette; Vervoordeldonk, Margriet J.; Tak, Paul P.

    2010-01-01

    Collagen-induced arthritis (CIA) in mice is an animal model for rheumatoid arthritis (RA) and can be induced in DBA/1 and C57BL/6 mice using different protocols. The CIA model can be used to unravel mechanisms involved in the development of arthritis and is frequently used to study the effect of new

  14. Surfactant protein D is proatherogenic in mice

    DEFF Research Database (Denmark)

    Sorensen, Grith L; Madsen, Jens; Kejling, Karin

    2006-01-01

    Surfactant protein D (SP-D) is an important innate immune defense molecule that mediates clearance of pathogens and modulates the inflammatory response. Moreover, SP-D is involved in lipid homeostasis, and pulmonary accumulation of phospholipids has previously been observed in SP-D-deficient (Spd......-/-) mice. Atherogenesis involves both inflammation and lipid deposition, and we investigated the role of SP-D in the development of atherosclerosis. SP-D synthesis was localized to vascular endothelial cells. Atherosclerotic lesion areas were 5.6-fold smaller in the aortic roots in Spd-/- mice compared...... with wild-type C57BL/6N mice on an atherogenic diet. HDL cholesterol (HDL-C) was significantly elevated in Spd-/- mice. Treatment of Spd-/- mice with a recombinant fragment of human SP-D resulted in decreases of HDL-C (21%) as well as total cholesterol (26%), and LDL cholesterol (28%). Plasma TNF...

  15. Pion contamination in the MICE muon beam

    International Nuclear Information System (INIS)

    Adams, D.; Barclay, P.; Bayliss, V.; Brashaw, T.W.; Alekou, A.; Apollonio, M.; Barber, G.; Asfandiyarov, R.; Blondel, A.; De Bari, A.; Bayes, R.; Bertoni, R.; Bonesini, M.; Blackmore, V.J.; Blot, S.; Bogomilov, M.; Booth, C.N.; Bowring, D.; Boyd, S.; Bravar, U.

    2016-01-01

    The international Muon Ionization Cooling Experiment (MICE) will perform a systematic investigation of ionization cooling with muon beams of momentum between 140 and 240 MeV/c at the Rutherford Appleton Laboratory ISIS facility. The measurement of ionization cooling in MICE relies on the selection of a pure sample of muons that traverse the experiment. To make this selection, the MICE Muon Beam is designed to deliver a beam of muons with less than ∼1% contamination. To make the final muon selection, MICE employs a particle-identification (PID) system upstream and downstream of the cooling cell. The PID system includes time-of-flight hodoscopes, threshold-Cherenkov counters and calorimetry. The upper limit for the pion contamination measured in this paper is f π  < 1.4% at 90% C.L., including systematic uncertainties. Therefore, the MICE Muon Beam is able to meet the stringent pion-contamination requirements of the study of ionization cooling

  16. Pion contamination in the MICE muon beam

    CERN Document Server

    Bogomilov, M.; Vankova-Kirilova, G.; Bertoni, R.; Bonesini, M.; Chignoli, F.; Mazza, R.; Palladino, V.; de Bari, A.; Cecchet, G.; Capponi, M.; Iaciofano, A.; Orestano, D.; Pastore, F.; Tortora, L.; Kuno, Y.; Sakamoto, H.; Ishimoto, S.; Japan, Ibaraki; Filthaut, F.; Hansen, O.M.; Ramberger, S.; Vretenar, M.; Asfandiyarov, R.; Blondel, A.; Drielsma, F.; Karadzhov, Y.; Charnley, G.; Collomb, N.; Gallagher, A.; Grant, A.; Griffiths, S.; Hartnett, T.; Martlew, B.; Moss, A.; Muir, A.; Mullacrane, I.; Oates, A.; Owens, P.; Stokes, G.; Warburton, P.; White, C.; Adams, D.; Barclay, P.; Bayliss, V.; Bradshaw, T.W.; Courthold, M.; Francis, V.; Fry, L.; Hayler, T.; Hills, M.; Lintern, A.; Macwaters, C.; Nichols, A.; Preece, R.; Ricciardi, S.; Rogers, C.; Stanley, T.; Tarrant, J.; Watson, S.; Wilson, A.; Bayes, R.; Nugent, J.C.; Soler, F.J.P.; Cooke, P.; Gamet, R.; Alekou, A.; Apollonio, M.; Barber, G.; Colling, D.; Dobbs, A.; Dornan, P.; Hunt, C.; Lagrange, J-B.; Long, K.; Martyniak, J.; Middleton, S.; Pasternak, J.; Santos, E.; Savidge, T.; Uchida, M.A.; Blackmore, V.J.; Carlisle, T.; Cobb, J.H.; Lau, W.; Rayner, M.A.; Tunnell, C.D.; Booth, C.N.; Hodgson, P.; Langlands, J.; Nicholson, R.; Overton, E.; Robinson, M.; Smith, P.J.; Dick, A.; Ronald, K.; Speirs, D.; Whyte, C.G.; Young, A.; Boyd, S.; Franchini, P.; Greis, J.R.; Pidcott, C.; Taylor, I.; Gardener, R.; Kyberd, P.; Littlefield, M.; Nebrensky, J.J.; Bross, A.D.; Fitzpatrick, T.; Leonova, M.; Moretti, A.; Neuffer, D.; Popovic, M.; Rubinov, P.; Rucinski, R.; Roberts, T.J.; Bowring, D.; DeMello, A.; Gourlay, S.; Li, D.; Prestemon, S.; Virostek, S.; Zisman, M.; Drews, M.; Hanlet, P.; Kafka, G.; Kaplan, D.M.; Rajaram, D.; Snopok, P.; Torun, Y.; Winter, M.; Blot, S.; Kim, Y.K.; Bravar, U.; Onel, Y.; Cremaldi, L.M.; Hart, T.L.; Luo, T.; Sanders, D.A.; Summers, D.J.; Cline, D.; Yang, X.; Coney, L.; Hanson, G.G.; Heidt, C.

    2016-01-01

    The international Muon Ionization Cooling Experiment (MICE) will perform a systematic investigation of ionization cooling with muon beams of momentum between 140 and 240\\,MeV/c at the Rutherford Appleton Laboratory ISIS facility. The measurement of ionization cooling in MICE relies on the selection of a pure sample of muons that traverse the experiment. To make this selection, the MICE Muon Beam is designed to deliver a beam of muons with less than $\\sim$1\\% contamination. To make the final muon selection, MICE employs a particle-identification (PID) system upstream and downstream of the cooling cell. The PID system includes time-of-flight hodoscopes, threshold-Cherenkov counters and calorimetry. The upper limit for the pion contamination measured in this paper is $f_\\pi < 1.4\\%$ at 90\\% C.L., including systematic uncertainties. Therefore, the MICE Muon Beam is able to meet the stringent pion-contamination requirements of the study of ionization cooling.

  17. Mobile optogenetic modules for mice

    Science.gov (United States)

    Rusakov, Konstantin; Radzewicz, Czesław; Czajkowski, Rafał; Konopka, Witold; Chilczuk, Joanna

    2017-08-01

    We present a set of novel optogenetic devices for mice freely moving in cages. The purpose of the devices is to stimulate specific brain regions using light. The devices we have constructed consist of an electrical connector, cannula and micro- LED chip operating at 470 nm as light source for delivering light into the stimulated region of the mouse brain. We have also demonstrated light conversion from 470 nm to 590 nm by applying a silicate orange phosphor directly to the LED chip. The measured conversion efficiency is approximately 80% for ZIP595I phosphor. We discuss the properties of various forms of implant needles with respect to the ease of LED attachment and experimental validation of the constructed optogenetic implants.

  18. Analysis of Pathogenesis of Autoimmune Insulitis in NOD Mice: Adoptive Transfer Experiments of Insulitis in ILI and NOD Nude Mice

    OpenAIRE

    Nakamura, Moritaka; Nishimura, Masahiko; Koide, Yukio; Takato, O.Yoshida

    2003-01-01

    In an effort to study the pathophysiological events in the development of insulitis in NOD mice, we have developed ILI- and NOD-nu/nu mice. ILI mice are a nondiabetic inbred strain but are derived from the same Jcl:ICR mouse as NOD mice and share the same H-2 allotype with NOD mice. Splenocytes and CD4+ cells from diabetic NOD mice appeared to transfer insulitis to ILI-nu/nu mice, suggesting that ILI mice already express autoantigen(s) responsible for insulitis. But reciprocal thymic grafts f...

  19. Bodyweight Assessment of Enamelin Null Mice

    Directory of Open Access Journals (Sweden)

    Albert H.-L. Chan

    2013-01-01

    Full Text Available The Enam null mice appear to be smaller than wild-type mice, which prompted the hypothesis that enamel defects negatively influence nutritional intake and bodyweight gain (BWG. We compared the BWG of Enam−/− and wild-type mice from birth (D0 to Day 42 (D42. Wild-type (WT and Enam−/− (N mice were given either hard chow (HC or soft chow (SC. Four experimental groups were studied: WTHC, WTSC, NHC, and NSC. The mother’s bodyweight (DBW and the average litter bodyweight (ALBW were obtained from D0 to D21. After D21, the pups were separated from the mother and provided the same type of food. Litter bodyweights were measured until D42. ALBW was compared at 7-day intervals using one-way ANOVA, while the influence of DBW on ALBW was analyzed by mixed-model analyses. The ALBW of Enam−/− mice maintained on hard chow (NHC was significantly lower than the two WT groups at D21 and the differences persisted into young adulthood. The ALBW of Enam−/− mice maintained on soft chow (NSC trended lower, but was not significantly different than that of the WT groups. We conclude that genotype, which affects enamel integrity, and food hardness influence bodyweight gain in postnatal and young adult mice.

  20. Chronotoxicity of glufosinate ammonium in mice.

    Science.gov (United States)

    Yoshiyama, Y; Kobayashi, T; Kondo, R; Tomonaga, F; Ohwada, T

    1995-02-01

    The effect of a circadian-stage dependent dosing schedule on the toxicity of glufosinate was studied in mice. Male ICR mice were housed in a standardized 12:12 light:dark cycle for 3 w. Each animal was given 1500 or 3000 mg glufosinate/kg po. A highly significant circadian rhythm occurred in the resulting mortality, with the highest mortality from doses given during the light phase and the lowest from doses administered during the dark phase. The circadian-stage dependent dosing schedule had a marked influence on the pattern of acute glufosinate toxicity in mice.

  1. Chemical sensitizers for hypoxic cells: a decade of experience in clinical radiotherapy

    Energy Technology Data Exchange (ETDEWEB)

    Dische, S [Mount Vernon Hospital, Northwood (UK)

    1985-02-01

    The clinical work with chemical agents to restore the radiosensitivity of hypoxic cells began in 1973 with metronidazole, misonidazole was first given in 1974. The results so far recorded of the clinical trials with misonidazole have been generally disappointing. Hypoxic cells must exist in all human tumours presenting for treatment and it is, however, probable that the oxygen effect is an important one at all dose fractionation regimes employed in radiotherapy but, after conventional fractionated radiotherapy, hypoxia may be a reason for failure in only a proportion of cases. The most important factor underlying the failure of misonidazole to acheive useful advantage is undoubtedly the low radiosensitizing concentrations achievable with the permitted dose of this neurotoxic drug. New drugs are under development and some have different dose-limiting toxicity. Those showing promise at this time are the Stanford compound, SR-2508 and the Roche compounds, Ro 03-8799. It is possible that the greatest sensitization with the greatest tolerance will be achieved by a combination of drugs.

  2. Principles of Economic Rationality in Mice.

    Science.gov (United States)

    Rivalan, Marion; Winter, York; Nachev, Vladislav

    2017-12-12

    Humans and non-human animals frequently violate principles of economic rationality, such as transitivity, independence of irrelevant alternatives, and regularity. The conditions that lead to these violations are not completely understood. Here we report a study on mice tested in automated home-cage setups using rewards of drinking water. Rewards differed in one of two dimensions, volume or probability. Our results suggest that mouse choice conforms to the principles of economic rationality for options that differ along a single reward dimension. A psychometric analysis of mouse choices further revealed that mice responded more strongly to differences in probability than to differences in volume, despite equivalence in return rates. This study also demonstrates the synergistic effect between the principles of economic rationality and psychophysics in making quantitative predictions about choices of healthy laboratory mice. This opens up new possibilities for the analyses of multi-dimensional choice and the use of mice with cognitive impairments that may violate economic rationality.

  3. Immunity to Trichinella spiralis in irradiated mice

    International Nuclear Information System (INIS)

    Wakelin, D.; Wilson, M.M.

    1980-01-01

    Irradiation prevented the accelerated expulsion of Trichinella spiralis from mice immunized by transfer of immune mesenteric lymph node cells (IMLNC) or by prior infection. Nevertheless, worms in irradiated immune mice were smaller and less fecund than those in controls. In adoptively immunized and irradiated mice expulsion could not be achieved by increasing the numbers of IMLNC transferred, although the effect upon worm length was more severe. Thus IMLNC express a direct, anti-worm immunity which is independent of their role in worm expulsion. IMLNC cause expulsion in irradiated mice only when adequate levels of bone marrow-derived cells are available. The results are discussed in terms of a possible antibody-mediated basis for direct anti-worm immunity. (author)

  4. Aged mice have increased inflammatory monocyte concentration ...

    Indian Academy of Sciences (India)

    monocytes from old as compared with those from young mice. The increased classic .... several instances where the isotype control antibodies stained in a similar position but at a ..... responses in young and older adults. J. Infect. Dis. 195.

  5. Bortezomib alters sour taste sensitivity in mice

    Directory of Open Access Journals (Sweden)

    Akihiro Ohishi

    Full Text Available Chemotherapy-induced taste disorder is one of the critical issues in cancer therapy. Bortezomib, a proteasome inhibitor, is a key agent in multiple myeloma therapy, but it induces a taste disorder. In this study, we investigated the characteristics of bortezomib-induced taste disorder and the underlying mechanism in mice. Among the five basic tastes, the sour taste sensitivity of mice was significantly increased by bortezomib administration. In bortezomib-administered mice, protein expression of PKD2L1 was increased. The increased sour taste sensitivity induced by bortezomib returned to the control level on cessation of its administration. These results suggest that an increase in protein expression of PKD2L1 enhances the sour taste sensitivity in bortezomib-administered mice, and this alteration is reversed on cessation of its administration. Keywords: Taste disorder, Bortezomib, Sour taste, Chemotherapy, Adverse effect

  6. Cytochrome P450 humanised mice

    Directory of Open Access Journals (Sweden)

    Gonzalez Frank J

    2004-05-01

    Full Text Available Abstract Humans are exposed to countless foreign compounds, typically referred to as xenobiotics. These can include clinically used drugs, environmental pollutants, food additives, pesticides, herbicides and even natural plant compounds. Xenobiotics are metabolised primarily in the liver, but also in the gut and other organs, to derivatives that are more easily eliminated from the body. In some cases, however, a compound is converted to an electrophile that can cause cell toxicity and transformation leading to cancer. Among the most important xenobiotic-metabolising enzymes are the cytochromes P450 (P450s. These enzymes represent a superfamily of multiple forms that exhibit marked species differences in their expression and catalytic activities. To predict how humans will metabolise xenobiotics, including drugs, human liver extracts and recombinant P450s have been used. New humanised mouse models are being developed which will be of great value in the study of drug metabolism, pharmacokinetics and pharmacodynamics in vivo, and in carrying out human risk assessment of xenobiotics. Humanised mice expressing CYP2D6 and CYP3A4, two major drug-metabolising P450s, have revealed the feasibility of this approach.

  7. Cytochrome P450 humanised mice

    Science.gov (United States)

    2004-01-01

    Humans are exposed to countless foreign compounds, typically referred to as xenobiotics. These can include clinically used drugs, environmental pollutants, food additives, pesticides, herbicides and even natural plant compounds. Xenobiotics are metabolised primarily in the liver, but also in the gut and other organs, to derivatives that are more easily eliminated from the body. In some cases, however, a compound is converted to an electrophile that can cause cell toxicity and transformation leading to cancer. Among the most important xenobiotic-metabolising enzymes are the cytochromes P450 (P450s). These enzymes represent a superfamily of multiple forms that exhibit marked species differences in their expression and catalytic activities. To predict how humans will metabolise xenobiotics, including drugs, human liver extracts and recombinant P450s have been used. New humanised mouse models are being developed which will be of great value in the study of drug metabolism, pharmacokinetics and pharmacodynamics in vivo, and in carrying out human risk assessment of xenobiotics. Humanised mice expressing CYP2D6 and CYP3A4, two major drug-metabolising P450s, have revealed the feasibility of this approach. PMID:15588489

  8. Reduced immune responses in chimeric mice engrafted with bone marrow cells from mice with airways inflammation.

    Science.gov (United States)

    Scott, Naomi M; Ng, Royce L X; McGonigle, Terence A; Gorman, Shelley; Hart, Prue H

    2015-11-01

    During respiratory inflammation, it is generally assumed that dendritic cells differentiating from the bone marrow are immunogenic rather than immunoregulatory. Using chimeric mice, the outcomes of airways inflammation on bone marrow progenitor cells were studied. Immune responses were analyzed in chimeric mice engrafted for >16 weeks with bone marrow cells from mice with experimental allergic airways disease (EAAD). Responses to sensitization and challenge with the allergen causing inflammation in the bone marrow-donor mice were significantly reduced in the chimeric mice engrafted with bone marrow cells from mice with EAAD (EAAD-chimeric). Responses to intranasal LPS and topical fluorescein isothiocyanate (non-specific challenges) were significantly attenuated. Fewer activated dendritic cells from the airways and skin of the EAAD-chimeric mice could be tracked to the draining lymph nodes, and may contribute to the significantly reduced antigen/chemical-induced hypertrophy in the draining nodes, and the reduced immune responses to sensitizing allergens. Dendritic cells differentiating in vitro from the bone marrow of >16 weeks reconstituted EAAD-chimeric mice retained an ability to poorly prime immune responses when transferred into naïve mice. Dendritic cells developing from bone marrow progenitors during airways inflammation are altered such that daughter cells have reduced antigen priming capabilities.

  9. Responses of Male C57BL/6N Mice to Observing the Euthanasia of Other Mice

    Science.gov (United States)

    Boivin, Gregory P; Bottomley, Michael A; Grobe, Nadja

    2016-01-01

    The AVMA Panel on Euthanasia recommends that sensitive animals should not be present during the euthanasia of others, especially of their own species, but does not provide guidelines on how to identify a sensitive species. To determine if mice are a sensitive species we reviewed literature on empathy in mice, and measured the cardiovascular and activity response of mice observing euthanasia of conspecifics. We studied male 16-wk-old C57BL/6N mice and found no increase in cardiovascular parameters or activity in the response of the mice to observing CO2 euthanasia. Mice observing decapitation had an increase in all values, but this was paralleled by a similar increase during mock decapitations in which no animals were handled or euthanized. We conclude that CO2 euthanasia of mice does not have an impact on other mice in the room, and that euthanasia by decapitation likely only has an effect due to the noise of the guillotine. We support the conceptual idea that mice are both a sensitive species and display empathy, but under the controlled circumstances of the euthanasia procedures used in this study there was no signaling of stress to witnessing inhabitants in the room. PMID:27423146

  10. Wound Healing in Mac-1 Deficient Mice

    Science.gov (United States)

    2017-05-01

    Dentistry, University of Illinois at Chicago, Chicago, IL, USA. 2 Department of Defense Biotechnology High Performance Computing Software...study, we used a commercially available Mac-1 deficient strain to examine whether this deficit 5 extends to slightly smaller wounds and incisional...levels of Collagen I and Collagen III in wounds from the two strains of mice at any time point. Unwounded skin from both WT and Mac-1 -/- mice contained

  11. Normal Conducting RF Cavity for MICE

    International Nuclear Information System (INIS)

    Li, D.; DeMello, A.; Virostek, S.; Zisman, M.; Summers, D.

    2010-01-01

    Normal conducting RF cavities must be used for the cooling section of the international Muon Ionization Cooling Experiment (MICE), currently under construction at Rutherford Appleton Laboratory (RAL) in the UK. Eight 201-MHz cavities are needed for the MICE cooling section; fabrication of the first five cavities is complete. We report the cavity fabrication status including cavity design, fabrication techniques and preliminary low power RF measurements.

  12. Metabolic characteristics of long-lived mice

    Directory of Open Access Journals (Sweden)

    Andrzej eBartke

    2012-12-01

    Full Text Available Genetic suppression of insulin/insulin-like growth factor signaling (IIS can extend longevity in worms, insects, and mammals. In laboratory mice, mutations with the greatest, most consistent, and best documented positive impact on lifespan are those that disrupt growth hormone (GH release or actions. These mutations lead to major alterations in IIS but also have a variety of effects that are not directly related to the actions of insulin or insulin-like growth factor (IGF-1. Long-lived GH-resistant GHRKO mice with targeted disruption of the GH receptor gene, as well as Ames dwarf (Prop1df and Snell dwarf (Pit1dw mice lacking GH (along with prolactin and TSH, are diminutive in size and have major alterations in body composition and metabolic parameters including increased subcutaneous adiposity, increased relative brain weight, small liver, hypoinsulinemia, mild hypoglycemia, increased adiponectin levels and insulin sensitivity, and reduced serum lipids. Body temperature is reduced in Ames, Snell, and female GHRKO mice. Indirect calorimetry revealed that both Ames dwarf and GHRKO mice utilize more oxygen per gram (g of body weight than sex- and age-matched normal animals from the same strain. They also have reduced respiratory quotient (RQ, implying greater reliance on fats, as opposed to carbohydrates, as an energy source. Differences in oxygen consumption (VO2 were seen in animals fed or fasted during the measurements as well as in animals that had been exposed to 30% calorie restriction or every-other-day feeding. However, at the thermoneutral temperature of 30°C, VO2 did not differ between GHRKO and normal mice. Thus, the increased metabolic rate of the GHRKO mice, at a standard animal room temperature of 23°C, is apparently related to increased energy demands for thermoregulation in these diminutive animals. We suspect that increased oxidative metabolism combined with enhanced fatty acid oxidation contribute to the extended longevity of

  13. Sensibility of 25 Trichomonas vaginalis isolates from Shiyan Region to metronidazole in vitro%湖北十堰地区25例阴道毛滴虫分离株对灭滴灵敏感性分析

    Institute of Scientific and Technical Information of China (English)

    杨树国; 张光玉; 杨宏伟

    2012-01-01

    目的 检测十堰地区阴道毛滴虫十堰分离株对灭滴灵的敏感性,分析本地区滴虫多分离株灭滴灵耐药性总体趋势.方法 收集阴道毛滴虫临床分离株25株,体外纯培养,设不同灭滴灵药物组,终浓度分别为:50μg/ml、31.25μg/ml、25 μg/ml、15.63 μg/ml、7.81 μg/ml、3.91 μg/ml、1.95 μg/ml、0 μg/ml,置37℃培养,分别于4、8、12、24h观察虫体生长存活情况,计算各株滴虫各时间点死亡率,对各时间点死亡率进行汇总并分析灭滴灵敏感性浓度区间分布.结果 高浓度组(50μg/m1、31.25 μg/ml、25 μg/ml、15.63 μg/m 、7.81 μg/ml)培养12h,滴虫死亡率均为100%,3.91 μg/ml浓度作用24h,滴虫死亡率为96%(24/25),1株滴虫死亡率为98.73%.结论 十堰地区阴道毛滴虫分离株对灭滴灵总体较敏感,24株体外24h有效最低杀虫浓度区间为1.95 ~ 3.91 μg/ml,1株滴虫为3.91~7.81 μg/ml.%Objective To observe the sensibility of 25 Triehomonas vaginalis isolates fromShiyan to metronidazole in vitro. Methods The 25 isolates of Trichomonas vaginalis were collected and cultivated four generationsby cultivation in8 tubes to logarithmic phage and the death rate was counted and the sensitivity range of Trichomonas vaginalis to different concentrations of metronidazole at concentrations of 50 μg/ml, 31.25 μg/ml, 25 μg/ml, 15.63 μg/ml , 7.81 μg/ml,3.91 μg/ml, 1.95 μg/ml, 0 μg/ml was observed 4, 8, 12 and 24 hours later .Results The death rate of 25 isolates was 100% 12 hours after incubation at the concentration of 50 μg/ml, 31.25 μg/ml、25 μg/ml、15.63 μg/m and 7.81 μg/ml respectively. Death rate was 100% 24 hours after contact, but one isolate was 98.73% at the concentration of 3.91 jig/ml. Conclusion Trichomonas vaginalis isolates were sensitive to metronidazole in general. Minimum lethal concentration(MLC) of 24 isolates was 1.95 ~ 3.91 μg/ml.

  14. Normal macrophage function in copper deficient mice

    International Nuclear Information System (INIS)

    Lukasewycz, O.A.; Kolquist, K.L.; Prohaska, J.R.

    1986-01-01

    Copper deficiency (-Cu) was produced in C57 BL and C58 mice by feeding a low copper diet (modified AIN-76A) from birth. Mice given supplemental copper in the drinking water (+Cu) served as controls. Copper status was monitored by assay of ceruloplasmin (CP) activity. Macrophages (M0) were obtained from matched +Cu and -Cu male 7 week-old mice by peritoneal lavage 3 days after thioglycollate stimulation. M0 were assayed in terms of lipopolysaccharide-induced hexose monophosphate shunt activity by monitoring 14 CO 2 production from [1- 14 C]-glucose and by the determination of phagocytic index using fluorescein labelled latex bead ingestion. M0 from -Cu mice were equivalent to those of +Cu mice in both these parameters. However, superoxide dismutase and cytochrome oxidase activities were both significantly lower in -Cu M0, confirming a functional copper deficiency. Previous results from this laboratory have shown that -Cu mice have a decreased antibody response to sheep erythrocyte antigens and a diminished reactivity to B and T cell mitogens. These immunological insufficiencies appear to be proportional to the severity of copper depletion as determined by CP levels. Furthermore, -Cu lymphocytes exhibit depressed mixed lymphocyte reactivity consistent with alterations at the membrane surface. The present results suggest that M0/monocytes are less severely affected than lymphocytes in copper deficiency states

  15. Men and mice: Relating their ages.

    Science.gov (United States)

    Dutta, Sulagna; Sengupta, Pallav

    2016-05-01

    Since the late 18th century, the murine model has been widely used in biomedical research (about 59% of total animals used) as it is compact, cost-effective, and easily available, conserving almost 99% of human genes and physiologically resembling humans. Despite the similarities, mice have a diminutive lifespan compared to humans. In this study, we found that one human year is equivalent to nine mice days, although this is not the case when comparing the lifespan of mice versus humans taking the entire life at the same time without considering each phase separately. Therefore, the precise correlation of age at every point in their lifespan must be determined. Determining the age relation between mice and humans is necessary for setting up experimental murine models more analogous in age to humans. Thus, more accuracy can be obtained in the research outcome for humans of a specific age group, although current outcomes are based on mice of an approximate age. To fill this gap between approximation and accuracy, this review article is the first to establish a precise relation between mice age and human age, following our previous article, which explained the relation in ages of laboratory rats with humans in detail. Copyright © 2015 Elsevier Inc. All rights reserved.

  16. Skewed X-inactivation in cloned mice

    International Nuclear Information System (INIS)

    Senda, Sho; Wakayama, Teruhiko; Yamazaki, Yukiko; Ohgane, Jun; Hattori, Naka; Tanaka, Satoshi; Yanagimachi, Ryuzo; Shiota, Kunio

    2004-01-01

    In female mammals, dosage compensation for X-linked genes is accomplished by inactivation of one of two X chromosomes. The X-inactivation ratio (a percentage of the cells with inactivated maternal X chromosomes in the whole cells) is skewed as a consequence of various genetic mutations, and has been observed in a number of X-linked disorders. We previously reported that phenotypically normal full-term cloned mouse fetuses had loci with inappropriate DNA methylation. Thus, cloned mice are excellent models to study abnormal epigenetic events in mammalian development. In the present study, we analyzed X-inactivation ratios in adult female cloned mice (B6C3F1). Kidneys of eight naturally produced controls and 11 cloned mice were analyzed. Although variations in X-inactivation ratio among the mice were observed in both groups, the distributions were significantly different (Ansary-Bradley test, P < 0.01). In particular, 2 of 11 cloned mice showed skewed X-inactivation ratios (19.2% and 86.8%). Similarly, in intestine, 1 of 10 cloned mice had a skewed ratio (75.7%). Skewed X-inactivation was observed to various degrees in different tissues of different individuals, suggesting that skewed X-inactivation in cloned mice is the result of secondary cell selection in combination with stochastic distortion of primary choice. The present study is the first demonstration that skewed X-inactivation occurs in cloned animals. This finding is important for understanding both nuclear transfer technology and etiology of X-linked disorders

  17. Lovastatin protects against experimental plague in mice.

    Directory of Open Access Journals (Sweden)

    Saravanan Ayyadurai

    Full Text Available BACKGROUND: Plague is an ectoparasite-borne deadly infection caused by Yersinia pestis, a bacterium classified among the group A bioterrorism agents. Thousands of deaths are reported every year in some African countries. Tetracyclines and cotrimoxazole are used in the secondary prophylaxis of plague in the case of potential exposure to Y. pestis, but cotrimoxazole-resistant isolates have been reported. There is a need for additional prophylactic measures. We aimed to study the effectiveness of lovastatin, a cholesterol-lowering drug known to alleviate the symptoms of sepsis, for plague prophylaxis in an experimental model. METHODOLOGY: Lovastatin dissolved in Endolipide was intraperitoneally administered to mice (20 mg/kg every day for 6 days prior to a Y. pestis Orientalis biotype challenge. Non-challenged, lovastatin-treated and challenged, untreated mice were also used as control groups in the study. Body weight, physical behavior and death were recorded both prior to infection and for 10 days post-infection. Samples of the blood, lungs and spleen were collected from dead mice for direct microbiological examination, histopathology and culture. The potential antibiotic effect of lovastatin was tested on blood agar plates. CONCLUSIONS/SIGNIFICANCE: Lovastatin had no in-vitro antibiotic effect against Y. pestis. The difference in the mortality between control mice (11/15; 73.5% and lovastatin-treated mice (3/15; 20% was significant (P<0.004; Mantel-Haenszel test. Dead mice exhibited Y. pestis septicemia and inflammatory destruction of lung and spleen tissues not seen in lovastatin-treated surviving mice. These data suggest that lovastatin may help prevent the deadly effects of plague. Field observations are warranted to assess the role of lovastatin in the prophylaxis of human plague.

  18. Chronic Co-species Housing Mice and Rats Increased the Competitiveness of Male Mice.

    Science.gov (United States)

    Liu, Ying-Juan; Li, Lai-Fu; Zhang, Yao-Hua; Guo, Hui-Fen; Xia, Min; Zhang, Meng-Wei; Jing, Xiao-Yuan; Zhang, Jing-Hua; Zhang, Jian-Xu

    2017-03-01

    Rats are predators of mice in nature. Nevertheless, it is a common practice to house mice and rats in a same room in some laboratories. In this study, we investigated the behavioral and physiological responsively of mice in long-term co-species housing conditions. Twenty-four male mice were randomly assigned to their original raising room (control) or a rat room (co-species-housed) for more than 6 weeks. In the open-field and light-dark box tests, the behaviors of the co-species-housed mice and controls were not different. In a 2-choice test of paired urine odors [rabbit urine (as a novel odor) vs. rat urine, cat urine (as a natural predator-scent) vs. rabbit urine, and cat urine vs. rat urine], the co-species-housed mice were more ready to investigate the rat urine odor compared with the controls and may have adapted to it. In an encounter test, the rat-room-exposed mice exhibited increased aggression levels, and their urines were more attractive to females. Correspondingly, the levels of major urinary proteins were increased in the co-species-housed mouse urine, along with some volatile pheromones. The serum testosterone levels were also enhanced in the co-species-housed mice, whereas the corticosterone levels were not different. The norepinephrine, dopamine, and 5-HT levels in the right hippocampus and striatum were not different between the 2. Our findings indicate that chronic co-species housing results in adaptation in male mice; furthermore, it appears that long-term rat-odor stimuli enhance the competitiveness of mice, which suggests that appropriate predator-odor stimuli may be important to the fitness of prey animals. © The Author 2017. Published by Oxford University Press. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.

  19. Effectiveness of BCG vaccination to aged mice

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    Ito Tsukasa

    2010-09-01

    Full Text Available Abstract Background The tuberculosis (TB still increases in the number of new cases, which is estimated to approach 10 million in 2010. The number of aged people has been growing all over the world. Ageing is one of risk factors in tuberculosis because of decreased immune responses in aged people. Mycobacterium bovis Bacillus Calmette Guérin (BCG is a sole vaccine currently used for TB, however, the efficacy of BCG in adults is still a matter of debate. Emerging the multidrug resistant Mycobacterium tuberculosis (MDR-TB make us to see the importance of vaccination against TB in new light. In this study, we evaluated the efficacy of BCG vaccination in aged mice. Results The Th1 responses, interferon-γ production and interleukin 2, in BCG inoculated aged mice (24-month-old were comparable to those of young mice (4- to 6-week-old. The protection activity of BCG in aged mice against Mycobacterium tuberculosis H37Rv was also the same as young mice. Conclusion These findings suggest that vaccination in aged generation is still effective for protection against tuberculosis.

  20. Otolith dysfunction alters exploratory movement in mice.

    Science.gov (United States)

    Blankenship, Philip A; Cherep, Lucia A; Donaldson, Tia N; Brockman, Sarah N; Trainer, Alexandria D; Yoder, Ryan M; Wallace, Douglas G

    2017-05-15

    The organization of rodent exploratory behavior appears to depend on self-movement cue processing. As of yet, however, no studies have directly examined the vestibular system's contribution to the organization of exploratory movement. The current study sequentially segmented open field behavior into progressions and stops in order to characterize differences in movement organization between control and otoconia-deficient tilted mice under conditions with and without access to visual cues. Under completely dark conditions, tilted mice exhibited similar distance traveled and stop times overall, but had significantly more circuitous progressions, larger changes in heading between progressions, and less stable clustering of home bases, relative to control mice. In light conditions, control and tilted mice were similar on all measures except for the change in heading between progressions. This pattern of results is consistent with otoconia-deficient tilted mice using visual cues to compensate for impaired self-movement cue processing. This work provides the first empirical evidence that signals from the otolithic organs mediate the organization of exploratory behavior, based on a novel assessment of spatial orientation. Copyright © 2017 Elsevier B.V. All rights reserved.

  1. Hematopoietic stem cell function in motheaten mice

    International Nuclear Information System (INIS)

    Shultz, L.D.; Bailey, C.L.; Coman, D.R.

    1983-01-01

    Mice homozygous for the autosomal recessive mutation ''motheaten'' have normal numbers of multipotential hematopoietic stem cells in the bone marrow and spleen as determined by spleen colony assay. Histologic examination shows no qualitative abnormality in morphology of stem cell colonies in recipients of bone marrow or spleen cells from motheaten mice. Despite the apparently normal ontogeny, distribution, and differentiative capacity of CFU stem cells, bone marrow and spleen cells from motheaten mice fail to save congenic +/+ lethally gamma-irradiated hosts. This impaired lifesparing capacity is not due to defective self-renewal but appears to be due in part to pulmonary hemorrhage from alveolar capillaries in the gamma-irradiated hosts. Treatment of motheaten mice with 500 R gamma-irradiation followed by reconstitution with normal bone marrow cells increases the lifespan of this mutant to 10 months of age. The early onset of pneumonitis and subsequent short lifespan of motheaten mice is determined at the level of progenitor cells in the bone marrow

  2. Catalase deletion promotes prediabetic phenotype in mice.

    Science.gov (United States)

    Heit, Claire; Marshall, Stephanie; Singh, Surrendra; Yu, Xiaoqing; Charkoftaki, Georgia; Zhao, Hongyu; Orlicky, David J; Fritz, Kristofer S; Thompson, David C; Vasiliou, Vasilis

    2017-02-01

    Hydrogen peroxide is produced endogenously and can be toxic to living organisms by inducing oxidative stress and cell damage. However, it has also been identified as a signal transduction molecule. By metabolizing hydrogen peroxide, catalase protects cells and tissues against oxidative damage and may also influence signal transduction mechanisms. Studies suggest that acatalasemic individuals (i.e., those with very low catalase activity) have a higher risk for the development of diabetes. We now report catalase knockout (Cat -/- ) mice, when fed a normal (6.5% lipid) chow, exhibit an obese phenotype that manifests as an increase in body weight that becomes more pronounced with age. The mice demonstrate altered hepatic and muscle lipid deposition, as well as increases in serum and hepatic triglycerides (TGs), and increased hepatic transcription and protein expression of PPARγ. Liver morphology revealed steatosis with inflammation. Cat -/- mice also exhibited pancreatic morphological changes that correlated with impaired glucose tolerance and increased fasting serum insulin levels, conditions consistent with pre-diabetic status. RNA-seq analyses revealed a differential expression of pathways and genes in Cat -/- mice, many of which are related to metabolic syndrome, diabetes, and obesity, such as Pparg and Cidec. In conclusion, the results of the present study show mice devoid of catalase develop an obese, pre-diabetic phenotype and provide compelling evidence for catalase (or its products) being integral in metabolic regulation. Copyright © 2016. Published by Elsevier Inc.

  3. Antitumour activity of cordycepin in mice.

    Science.gov (United States)

    Yoshikawa, Noriko; Nakamura, Kazuki; Yamaguchi, Yu; Kagota, Satomi; Shinozuka, Kazumasa; Kunitomo, Masaru

    2004-12-01

    1. The antitumour effect of orally administered cordycepin, a component isolated from water extracts of Cordyceps sinensis, was examined in mice inoculated with B16 melanoma (B16-BL6) cells. 2. B16-BL6 (1 x 10(6)) cells were inoculated subcutaneously into the right footpad of mice. At 2 weeks after the cell inoculation, the enlarged primary tumour lump was weighed. Cordycepin (0, 5 and 15 mg/kg per day) was administered orally to the mice for 2 weeks from the date of tumour inoculation. Cordycepin (15 mg/kg per day) significantly reduced by 36% the wet weight of the primary tumour lump compared to that of the untreated control mice, without any loss of bodyweight or systemic toxicity. 3. Cordycepin (15 mg/kg per day) administered orally for 2 weeks inhibited the tumour enlargement in the right thigh inoculated with B16-BL6 cells premixed with extracellular matrix (Matrigel). 4. These results indicate that orally administered cordycepin inhibits melanoma cell growth in mice with no adverse effects.

  4. Nitroimidazoles as hypoxic cell radiosensitizers and hypoxia probes: misonidazole, myths and mistakes.

    Science.gov (United States)

    Wardman, Peter

    2018-03-20

    Nitroimidazoles have been extensively explored as hypoxic cell radiosensitizers but have had limited clinical success, with efficacy restricted by toxicity. However, they have proven clinically useful as probes for tumour hypoxia. Both applications, and probably much of the dose-limiting toxicities, reflect the dominant chemical property of electron affinity or ease of reduction, associated with the nitro substituent in an aromatic structure. This single dominant property affords unusual, indeed extraordinary flexibility in drug or probe design, suggesting further development is possible in spite of earlier limitations, in particular building on the benefit of hindsight and an appreciation of errors made in earlier studies. The most notable errors were: the delay in viewing cellular thiol depletion as a likely common artefact in testing in vitro; slow recognition of pH-driven concentration gradients when compounds were weak acids and bases; and a failure to explore the possible involvement of pH and ascorbate in influencing hypoxia probe binding. The experience points to the need to involve a wider range of expertise than that historically involved in many laboratories when studying the effects of chemicals on radiation response or using diagnostic probes.

  5. Ultrastructural alterations in hypoxic EMT-6/RO cells treated with misonidazole

    International Nuclear Information System (INIS)

    Wilbur, D.C.; Mulcahy, R.T.

    1984-01-01

    Ultrastructural alterations in hypoxic EMT-6 tumor cells were quantitatively analyzed as a function of time in the presence and absence of 1.0mM MISO. Control and MISO-treated monolayer cultures were maintained in hypoxic chambers at 37 0 C. At intervals after initiation of hypoxia, the cells were fixed and prepared for electron microscopy. The major ultrastructural alterations observed in untreated and MISO-treated hypoxic cells included mitochondrial swelling and accumulation of cytoplasmic lipid vacuoles. Mean mitochondrial area and relative cytoplasmic area occupied by lipid vacuoles were determined morphometrically. Mitochondrial damage was also scored qualitatively based on distortions in configuration. In the absence of MISO both parameters of mitochondrial injury increased over a period of two hours, after which little further change was noted. A progressive increase in lipid vacuolization was also seen. In the presence of MISO, mitochondrial swelling and lipid vacuole formation were significantly increased. The proportion of irreversibly damaged mitochondria was markedly enhanced. MISO treatment also accelerated the expression of these changes. The accelerated expression of hypoxic-related injury in MISO treated cells suggests that cytotoxicity is related to accentuation of hypoxic injury, perhaps by inhibition of glycolysis

  6. Ghrelin reverses experimental diabetic neuropathy in mice

    Energy Technology Data Exchange (ETDEWEB)

    Kyoraku, Itaru; Shiomi, Kazutaka [Division of Neurology, Respirology, Endocrinology and Metabolism, Department of Internal Medicine, Faculty of Medicine, University of Miyazaki, Kiyotake, Miyazaki 889-1692 (Japan); Kangawa, Kenji [Department of Biochemistry, National Cardiovascular Center Research Institute, Osaka 565-8565 (Japan); Nakazato, Masamitsu, E-mail: nakazato@med.miyazaki-u.ac.jp [Division of Neurology, Respirology, Endocrinology and Metabolism, Department of Internal Medicine, Faculty of Medicine, University of Miyazaki, Kiyotake, Miyazaki 889-1692 (Japan)

    2009-11-20

    Ghrelin, an acylated peptide produced in the stomach, increases food intake and growth hormone secretion, suppresses inflammation and oxidative stress, and promotes cell survival and proliferation. We investigated the pharmacological potential of ghrelin in the treatment of polyneuropathy in uncontrolled streptozotocin (STZ)-induced diabetes in mice. Ghrelin or desacyl-ghrelin was administered daily for 4 weeks after STZ-induced diabetic polyneuropathy had developed. Ghrelin administration did not alter food intake, body weight gain, blood glucose levels, or plasma insulin levels when compared with mice given saline or desacyl-ghrelin administration. Ghrelin administration ameliorated reductions in motor and sensory nerve conduction velocities in diabetic mice and normalized their temperature sensation and plasma concentrations of 8-isoprostaglandin {alpha}, an oxidative stress marker. Desacyl-ghrelin failed to have any effect. Ghrelin administration in a mouse model of diabetes ameliorated polyneuropathy. Thus, ghrelin's effects represent a novel therapeutic paradigm for the treatment of this otherwise intractable disorder.

  7. Ghrelin reverses experimental diabetic neuropathy in mice

    International Nuclear Information System (INIS)

    Kyoraku, Itaru; Shiomi, Kazutaka; Kangawa, Kenji; Nakazato, Masamitsu

    2009-01-01

    Ghrelin, an acylated peptide produced in the stomach, increases food intake and growth hormone secretion, suppresses inflammation and oxidative stress, and promotes cell survival and proliferation. We investigated the pharmacological potential of ghrelin in the treatment of polyneuropathy in uncontrolled streptozotocin (STZ)-induced diabetes in mice. Ghrelin or desacyl-ghrelin was administered daily for 4 weeks after STZ-induced diabetic polyneuropathy had developed. Ghrelin administration did not alter food intake, body weight gain, blood glucose levels, or plasma insulin levels when compared with mice given saline or desacyl-ghrelin administration. Ghrelin administration ameliorated reductions in motor and sensory nerve conduction velocities in diabetic mice and normalized their temperature sensation and plasma concentrations of 8-isoprostaglandin α, an oxidative stress marker. Desacyl-ghrelin failed to have any effect. Ghrelin administration in a mouse model of diabetes ameliorated polyneuropathy. Thus, ghrelin's effects represent a novel therapeutic paradigm for the treatment of this otherwise intractable disorder.

  8. Magnetic biomineralisation in Huntington's disease transgenic mice

    International Nuclear Information System (INIS)

    Beyhum, W; Hautot, D; Dobson, J; Pankhurst, Q A

    2005-01-01

    The concentration levels of biogenic magnetite nanoparticles in transgenic R6/2 Huntington's disease (HD) mice have been investigated, using seven control and seven HD mice each from an 8 week-old litter and from a 12 week-old litter. Hysteresis and isothermal remnant magnetisation data were collected on a SQUID magnetometer, and analysed using a model comprising dia/paramagnetic, ferrimagnetic and superparamagnetic contributions, to extract the magnetite and ferritin concentrations present. It was found that magnetite was present in both superparamagnetic and blocked states. A larger spread and higher concentration of magnetite levels was found in the diseased mice for both the 8 week-old and 12 week-old batches, compared to the controls

  9. Mice prefer draught-free housing.

    Science.gov (United States)

    Krohn, T C; Hansen, A K

    2010-10-01

    An increasing number of rodents are housed in individually ventilated cage (IVC) systems, as these seem to be very effective for the protection of animals against infections, as well as protecting the staff against allergens. For the IVC systems to be properly ventilated, a huge amount of air has to be blown into the cage, which may cause a draught at animal level inside the cage. The aim of the present study was to evaluate the preferences of mice for differing levels of air speeds and air changes inside the cage. It has been concluded that mice do react to draughts, whereas they do not seem to be affected by a high number of air changes delivered without draught, which underlines the importance of applying draught-free IVC systems for mice.

  10. Intermittent hypoxia induces hyperlipidemia in lean mice.

    Science.gov (United States)

    Li, Jianguo; Thorne, Laura N; Punjabi, Naresh M; Sun, Cheuk-Kwan; Schwartz, Alan R; Smith, Philip L; Marino, Rafael L; Rodriguez, Annabelle; Hubbard, Walter C; O'Donnell, Christopher P; Polotsky, Vsevolod Y

    2005-09-30

    Obstructive sleep apnea, a syndrome leading to recurrent intermittent hypoxia (IH), has been associated previously with hypercholesterolemia, independent of underlying obesity. We examined the effects of experimentally induced IH on serum lipid levels and pathways of lipid metabolism in the absence and presence of obesity. Lean C57BL/6J mice and leptin-deficient obese C57BL/6J-Lep(ob) mice were exposed to IH for five days to determine changes in serum lipid profile, liver lipid content, and expression of key hepatic genes of lipid metabolism. In lean mice, exposure to IH increased fasting serum levels of total cholesterol, high-density lipoprotein (HDL) cholesterol, phospholipids (PLs), and triglycerides (TGs), as well as liver TG content. These changes were not observed in obese mice, which had hyperlipidemia and fatty liver at baseline. In lean mice, IH increased sterol regulatory element binding protein 1 (SREBP-1) levels in the liver, increased mRNA and protein levels of stearoyl-coenzyme A desaturase 1 (SCD-1), an important gene of TG and PL biosynthesis controlled by SREBP-1, and increased monounsaturated fatty acid content in serum, which indicated augmented SCD-1 activity. In addition, in lean mice, IH decreased protein levels of scavenger receptor B1, regulating uptake of cholesterol esters and HDL by the liver. We conclude that exposure to IH for five days increases serum cholesterol and PL levels, upregulates pathways of TG and PL biosynthesis, and inhibits pathways of cholesterol uptake in the liver in the lean state but does not exacerbate the pre-existing hyperlipidemia and metabolic disturbances in leptin-deficient obesity.

  11. Mapping pathological phenotypes in Reelin mutant mice

    Directory of Open Access Journals (Sweden)

    Caterina eMichetti

    2014-09-01

    Full Text Available Autism Spectrum Disorders (ASD are neurodevelopmental disorders with multifactorial origin characterized by social communication and behavioural perseveration deficits. Several studies showed an association between the reelin gene mutation and increased risk of ASD and a reduced reelin expression in some brain regions of ASD subjects, suggesting a role for reelin deficiency in ASD etiology. Reelin is a large extracellular matrix glycoprotein playing important roles during development of the central nervous system. To deeply investigate the role of reelin dysfunction as vulnerability factor in ASD, we investigated the behavioural, neurochemical and brain morphological features of reeler male mice. We recently reported a genotype-dependent deviation in ultrasonic vocal repertoire and a general delay in motor development in reeler pups. We now report that adult male heterozygous reeler mice did not show social behaviour and communication deficits during male-female social interactions. Wildtype and heterozygous mice also showed a typical light/dark locomotor activity profile, with a peak during the central interval of the dark phase. However, when faced with a mild stressful stimulus (a saline injection only heterozygous mice showed an over response to stress. At the end of the behavioural studies, we conducted high performance liquid chromatography and magnetic resonance imaging and spectroscopy to investigate whether reelin mutation influences brain monoamine and metabolites levels in regions involved in ASD. Low levels of dopamine in cortex and high levels of glutamate and taurine in hippocampus were detected in heterozygous mice, in line with clinical data collected on ASD children. Altogether, our data detected subtle but relevant neurochemical abnormalities in reeler mice supporting this mutant line, particularly male subjects, as a valid experimental model to estimate the contribution played by reelin deficiency in the global ASD

  12. The Memory of MICE: The Configuration Database

    International Nuclear Information System (INIS)

    Wilson, A J; Colling, D J; Hanlet, P

    2012-01-01

    The configuration database (CDB) is the memory of the Muon Ionisation Cooling Experiment (MICE). Its principle aim is to store temporal data associated with the running of the experiment; these data are used throughout the life cycle of experiment, from running the experiment through data analysis. The CDB also serves as a moderator in the MICE state machine by defining allowable operating states of subsystems depending on the overall state of MICE and other subsystems. Master and slave CDBs, with multiple mirrored pair raid arrays, have been set up in different parts of the site to increase resilience, as well as off site backups. Access to the CDB is via a Python API, which communicates with a WSDL interface provided by a web-service on the CDB. The priority is to ensure availability of the CDB in the experiment control room. The master CDB is located in the MICE control where it is only used by the running experiment. In the event of the failure of the master, the slave can easily be promoted to master. Read only access to the CDB for data analysis and reconstruction is provided by the slave which has an up to the minute copy of the data. As MICE is a precision experiment which will measure a 10% muon cooling effect with 1% precision, it is imperative that we minimize our systematic errors; the CDB will ensure reproducible and documented running conditions in a highly resilient manner. A description of the hardware and software used in the the MICE CDB will be described in what follows.

  13. Analysis of mice radiosensitivity depending on age

    International Nuclear Information System (INIS)

    Bogatyrev, A.V.; Timoshenko, S.I.; Nikanorova, N.G.; Sverdlov, A.G.

    1979-01-01

    In order to elucidate mechanisms of age variations in radiosensitivity of mice a study was made of the sensitivity of in vitro irradiated bone marrow stem cells, taken from animals of different age, and postradiation recovery of leukocyte content of peripheral blood and cellularity of bone marrow and spleen. Using the method of spleen colonies similar affections were revealed in bone marrow cells of animals of different age. The degree of recovery of the hemopoietic cell pool was significantly lower in newborn mice than in adults after exposure to a dose (LDsub(50/30)) equally effective with respect to mortality

  14. Radiation-induced diploid spermatids in mice

    International Nuclear Information System (INIS)

    Hacker-Klom, U.; Heiden, Th.; Otto, F.J.; Goehde, W.; Mauro, F.

    1989-01-01

    Diploid elongated spermatids of mice were enriched by flow cytometry and cell sorting using a new type of sorter (Partec). The sorted abnormal spermatids were identified morphologically and by nuclear area integration. The radiation-induced increase in the frequency of diploid elongated spermatids was monitored with time following acute X-ray exposure of mice. Dose-response curves for acute 60 Co-gamma and 14 MeV neutron irradiations yielded an RBE value of 4.3 for the doubling of the control level. (author)

  15. Action of apilite on radiosensitivity of mice

    International Nuclear Information System (INIS)

    Artemov, N.M.; Kon'kova, L.G.; Sergeyeva, L.I.

    1975-01-01

    A preparation of bee venom - apilite - has been administered to mice in different periods prior to and after the exposure to 600 and 500 r (6 and 10 μg/g, respectively). This preparation is freed from allergizating proteins and enzymes of the venom. Its basic active substance is polypeptid melittine. Apilite has been found to exert a protective effect: the survival of the experimental groups of mice is 27-44 per cent higher than that of the controls. It has also been revealed that apilite has a positive action on a number of indices of the peripheral blood of irradiated animals

  16. Radiation-induced diploid spermatids in mice

    Energy Technology Data Exchange (ETDEWEB)

    Hacker-Klom, U; Heiden, Th; Otto, F J; Goehde, W; Mauro, F

    1989-05-01

    Diploid elongated spermatids of mice were enriched by flow cytometry and cell sorting using a new type of sorter (Partec). The sorted abnormal spermatids were identified morphologically and by nuclear area integration. The radiation-induced increase in the frequency of diploid elongated spermatids was monitored with time following acute X-ray exposure of mice. Dose-response curves for acute /sup 60/Co-gamma and 14 MeV neutron irradiations yielded an RBE value of 4.3 for the doubling of the control level. (author).

  17. Cardiovascular phenotype in Smad3 deficient mice with renovascular hypertension.

    Science.gov (United States)

    Kashyap, Sonu; Warner, Gina; Hu, Zeng; Gao, Feng; Osman, Mazen; Al Saiegh, Yousif; Lien, Karen R; Nath, Karl; Grande, Joseph P

    2017-01-01

    Renovascular hypertension (RVH) has deleterious effects on both the kidney and the heart. TGF-β signaling through Smad3 directs tissue fibrosis in chronic injury models. In the 2-kidney 1-clip (2K1C) model of RVH, employing mice on the 129 genetic background, Smad3 deficiency (KO) protects the stenotic kidney (STK) from development of interstitial fibrosis. However, these mice have an increased incidence of sudden cardiac death following 2K1C surgery. The purpose of this study was to characterize the cardiovascular phenotype of these mice. Renal artery stenosis (RAS) was established in Wild-type (WT) and Smad3 KO mice (129 genetic background) by placement of a polytetrafluoroethylene cuff on the right renal artery. Mortality was 25.5% for KO mice with RAS, 4.1% for KO sham mice, 1.2% for WT with RAS, and 1.8% for WT sham mice. Myocardial tissue of mice studied at 3 days following surgery showed extensive myocyte necrosis in KO but not WT mice. Myocyte necrosis was associated with a rapid induction of Ccl2 expression, macrophage influx, and increased MMP-9 activity. At later time points, both KO and WT mice developed myocardial fibrosis. No aortic aneurysms or dissections were observed at any time point. Smad3 KO mice were backcrossed to the C57BL/6J strain and subjected to RAS. Sudden death was observed at 10-14 days following surgery in 62.5% of mice; necropsy revealed aortic dissections as the cause of death. As observed in the 129 mice, the STK of Smad3 KO mice on the C57BL/6J background did not develop significant chronic renal damage. We conclude that the cardiovascular manifestations of Smad3 deficient mice are strain-specific, with myocyte necrosis in 129 mice and aortic rupture in C57BL/6J mice. Future studies will define mechanisms underlying this strain-specific effect on the cardiovascular system.

  18. Introducing Clicker Training as a Cognitive Enrichment for Laboratory Mice.

    Science.gov (United States)

    Leidinger, Charlotte; Herrmann, Felix; Thöne-Reineke, Christa; Baumgart, Nadine; Baumgart, Jan

    2017-03-06

    Establishing new refinement strategies in laboratory animal science is a central goal in fulfilling the requirements of Directive 2010/63/EU. Previous research determined a profound impact of gentle handling protocols on the well-being of laboratory mice. By introducing clicker training to the keeping of mice, not only do we promote the amicable treatment of mice, but we also enable them to experience cognitive enrichment. Clicker training is a form of positive reinforcement training using a conditioned secondary reinforcer, the "click" sound of a clicker, which serves as a time bridge between the strengthened behavior and an upcoming reward. The effective implementation of the clicker training protocol with a cohort of 12 BALB/c inbred mice of each sex proved to be uncomplicated. The mice learned rather quickly when challenged with tasks of the clicker training protocol, and almost all trained mice overcame the challenges they were given (100% of female mice and 83% of male mice). This study has identified that clicker training for mice strongly correlates with reduced fear in the mice during human-mice interactions, as shown by reduced anxiety-related behaviors (e.g., defecation, vocalization, and urination) and fewer depression-like behaviors (e.g., floating). By developing a reliable protocol that can be easily integrated into the daily routine of the keeping of laboratory mice, the lifetime experience of welfare in the mice can be improved substantially.

  19. [Anatomy and histology characteristics of lymph node in nude mice].

    Science.gov (United States)

    Sun, R; Gao, B; Guo, C B

    2017-10-18

    To compare the differences of anatomical and histological characteristics of lymph nodes between BALB/c nude mice and BALB/c mice. Firstly, twenty BALB/c nude mice and twenty BALB/c mice were dissected by using a surgical microscope. Secondly, the differences of T cells and B cells at the lymph node were compared by the expressions of CD 3 and CD 20 immunohistochemistry dyes. There were, on average, 23 nodes per mouse contained within the large lymph node assembly in the BALB/c nude mouse. The anatomical features of the lymph node distribution in the nude mice were mainly found in the neck with relatively higher density. There were two lymph nodes both in the submandible lymph nodes group and in the superficial cervical lymph nodes group (the constituent ratios were 95% and 90%, respectively) in the BALB/c nude mice, but there were four lymph nodes (the constituent ratios were 95% and 90%, respectively) in the BALB/c mice. There were significant difference between the BALB/c nude mice and the BALB/c mice. Mostly there were two lymph nodes of deep cervical lymph nodes both in the BALB/c nude mice and the BALB/c mice (the constituent ratios were 95% and 100%, respectively). There were no significant difference between the BALB/c nude mice and the BALB/c mice. We confirmed that the number of CD 3 -positive T lymphocytes in lymph nodes of the nude mice decreased greatly as compared with the BALB/c mice. Expressions of CD3 in T cells were 95% and 100% in the BALB/c nude mice and in the BALB/c mice, respectively. There were significant differences between the BALB/c nude mice and the BALB/c mice. Expressions of CD20 in B cells were 95% and 100% in the BALB/c nude mice and in the BALB/c mice, respectively. There was no significant difference between the BALB/c nude mice and BALB/c mice. The anatomical pictures of lymph node distribution in the nude mouse will be benefit to those who are interested. The anatomical features of the lymph node local higher density in neck of

  20. Effect of cadmium chloride on hepatic lipid peroxidation in mice

    DEFF Research Database (Denmark)

    Andersen, H R; Andersen, O

    1988-01-01

    Intraperitoneal administration of cadmium chloride to 8-12 weeks old CBA-mice enhanced hepatic lipid peroxidation. A positive correlation between cadmium chloride dose and level of peroxidation was observed in both male and female mice. A sex-related difference in mortality was not observed...... but at a dose of 25 mumol CdCl2/kg the level of hepatic lipid peroxidation was higher in male mice than in female mice. The hepatic lipid peroxidation was not increased above the control level in 3 weeks old mice, while 6 weeks old mice responded with increased peroxidation as did 8-12 weeks old mice....... The mortality after an acute toxic dose of cadmium chloride was the same in the three age groups. Pretreatment of mice with several low intraperitoneal doses of cadmium chloride alleviated cadmium induced mortality and lipid peroxidation. The results demonstrate both age dependency and a protective effect...

  1. Effect of aging and radiation in mice of different genotypes

    International Nuclear Information System (INIS)

    Storer, J.B.

    1976-01-01

    Data are presented on the life span of nine inbred strains and five hybrid strains of mice based on 400 mice of each sex for inbred and 200 mice of each sex for hybrid. Some of these mice were exposed when 120 days old to 250 R or 450 R of x radiation delivered at a dose rate of 60 R/min. Data on strain, sample size, and mean survival times are presented in tables

  2. Hyperalgesic activity of kisspeptin in mice

    Directory of Open Access Journals (Sweden)

    Spampinato Simona

    2011-11-01

    Full Text Available Abstract Background Kisspeptin is a neuropeptide known for its role in the hypothalamic regulation of the reproductive axis. Following the recent description of kisspeptin and its 7-TM receptor, GPR54, in the dorsal root ganglia and dorsal horns of the spinal cord, we examined the role of kisspeptin in the regulation of pain sensitivity in mice. Results Immunofluorescent staining in the mouse skin showed the presence of GPR54 receptors in PGP9.5-positive sensory fibers. Intraplantar injection of kisspeptin (1 or 3 nmol/5 μl induced a small nocifensive response in naive mice, and lowered thermal pain threshold in the hot plate test. Both intraplantar and intrathecal (0.5 or 1 nmol/3 μl injection of kisspeptin caused hyperalgesia in the first and second phases of the formalin test, whereas the GPR54 antagonist, p234 (0.1 or 1 nmol, caused a robust analgesia. Intraplantar injection of kisspeptin combined with formalin enhanced TRPV1 phosphorylation at Ser800 at the injection site, and increased ERK1/2 phosphorylation in the ipsilateral dorsal horn as compared to naive mice and mice treated with formalin alone. Conclusion These data demonstrate for the first time that kisspeptin regulates pain sensitivity in rodents and suggest that peripheral GPR54 receptors could be targeted by novel drugs in the treatment of inflammatory pain.

  3. Infanticide: accounting for genetic variation in mice.

    Science.gov (United States)

    Svare, B; Kinsley, C H; Mann, M A; Broida, J

    1984-07-01

    Infanticide, the killing of young, is one of a number of sexually-dimorphic traits in mice that is dependent upon androgen stimulation during perinatal life and during adulthood. Genotype also influences infanticide in that males of some strains of mice (C57BL/6J) exhibit high levels of this behavior while males of other strains (DBA/2J) seldom kill young. The experiments conducted here show that strain differences in pup killing behavior exhibited by males are not related to postweaning social factors nor are they due to differences in perinatal, pubertal, or adult levels of circulating hormones. These results, in combination with those previously reported, suggest that strain differences in the tendency of mice to kill young may instead depend upon the interaction of genotypic features such as prenatal hormone titers and/or sensitivity to these hormones, as well as on extra organismic factors such as intrauterine position. A model for understanding the manner in which genes and hormones may interact to influence infanticide and other hormone dependent sexually-dimorphic behaviors in mice is presented.

  4. Circadian behaviour in neuroglobin deficient mice

    DEFF Research Database (Denmark)

    Hundahl, Christian A; Fahrenkrug, Jan; Hay-Schmidt, Anders

    2012-01-01

    on circadian behavior. Ngb-deficient and wild-type (wt) mice were placed in running wheels and their activity rhythms, endogenous period and response to light stimuli were investigated. The effect of Ngb deficiency on the expression of Period1 (Per1) and the immediate early gene Fos was determined after light...

  5. Anticonvulsant Activity of Argyreia speciosa in Mice.

    Science.gov (United States)

    Vyawahare, N S; Bodhankar, S L

    2009-03-01

    Argyreia speciosa commonly known as Vridha daraka in Sanskrit is one of the important plants used in indigenous system of medicine. The root is regarded as an alternative tonic and useful in the diseases of nervous system. To confirm the veracity of aforementioned claim, we have evaluated the anticonvulsant effect of the extract. In this investigation, the mice were pretreated with different doses of Argyreia speciosa extract (100, 200, 400 mg/kg) for 10 days and then, they were subjected to either pentylenetetrazole (80 mg/kg) or maximal electroshock seizures (50 mA, 0.2 s) treatment. The hydroalcoholic extract of Argyreia speciosa at the dose of 200 and 400 mg/kg significantly delayed the latency to the onset of first clonus as well as onset of death in unprotected mice and exhibited protection in 16.66% and 33.33% of pentylenetetrazole treated mice respectively. Whereas in case of maximal electroshock-seizures, the dose of 200 and 400 mg/kg significantly reduced the duration of hind limb extension and both the doses were statistically found to be equipotent. The reference standards, clonazepam (0.1 mg/kg) and phenytoin (20 mg/kg) provided complete protection. Thus, present study revealed anticonvulsant effect of Argyreia speciosa against pentylenetetrazole- and maximal electroshock-induced convulsions in mice.

  6. Reinstatement of Conditioned Suppression in Mice

    Directory of Open Access Journals (Sweden)

    Trinette Dirikx

    2006-03-01

    Full Text Available Return of fear after successful exposure therapy calls for a better understanding of the mechanisms of relapse. Classical conditioning research provides a useful framework for conceptualising the acquisition, extinction and reappearance of fear. The present paper focuses on reinstatement, the return of extinguished conditioned responses due to the experience of one or more unconditioned stimuli (USs after extinction. This phenomenon illustrates that unpredictable USs can lead to a return of fear after successful exposure. The data we present is one of the first demonstrations that conditioned suppression of instrumental behaviour can be used as an index of classical conditioning in laboratory mice. The procedure proves to be a promising instrument for assessing fear in mice, both in the context of research aimed at unravelling the functional characteristics of learning and memory in healthy mice and in the context of research aimed at unravelling the neurobiological substrate of psychiatric disorders, e.g., in studies with transgenic and knockout mice. Using this procedure, we report the first observation of reinstatement of conditioned suppression in this species.

  7. Skeletal muscle weakness in osteogenesis imperfecta mice.

    Science.gov (United States)

    Gentry, Bettina A; Ferreira, J Andries; McCambridge, Amanda J; Brown, Marybeth; Phillips, Charlotte L

    2010-09-01

    Exercise intolerance, muscle fatigue and weakness are often-reported, little-investigated concerns of patients with osteogenesis imperfecta (OI). OI is a heritable connective tissue disorder hallmarked by bone fragility resulting primarily from dominant mutations in the proα1(I) or proα2(I) collagen genes and the recently discovered recessive mutations in post-translational modifying proteins of type I collagen. In this study we examined the soleus (S), plantaris (P), gastrocnemius (G), tibialis anterior (TA) and quadriceps (Q) muscles of mice expressing mild (+/oim) and moderately severe (oim/oim) OI for evidence of inherent muscle pathology. In particular, muscle weight, fiber cross-sectional area (CSA), fiber type, fiber histomorphology, fibrillar collagen content, absolute, relative and specific peak tetanic force (P(o), P(o)/mg and P(o)/CSA respectively) of individual muscles were evaluated. Oim/oim mouse muscles were generally smaller, contained less fibrillar collagen, had decreased P(o) and an inability to sustain P(o) for the 300-ms testing duration for specific muscles; +/oim mice had a similar but milder skeletal muscle phenotype. +/oim mice had mild weakness of specific muscles but were less affected than their oim/oim counterparts which demonstrated readily apparent skeletal muscle pathology. Therefore muscle weakness in oim mice reflects inherent skeletal muscle pathology. Copyright © 2010 Elsevier B.V. All rights reserved.

  8. Protection of mice against Giardia muris infection.

    Science.gov (United States)

    Roberts-Thomson, I C; Mitchell, G F

    1979-01-01

    Strains of mice showing relatively rapid (BALB/c) and defective (C3H/He) spontaneous elimination of Giardia muris displayed marked differences in the degree of resistance to infection induced by prior injection of trophozoites in Freund complete adjuvant. PMID:468385

  9. Sleep deprivation impairs object recognition in mice

    NARCIS (Netherlands)

    Palchykova, S; Winsky-Sommerer, R; Meerlo, P; Durr, R; Tobler, Irene

    2006-01-01

    Many studies in animals and humans suggest that sleep facilitates learning, memory consolidation, and retrieval. Moreover, sleep deprivation (SD) incurred after learning, impaired memory in humans, mice, rats, and hamsters. We investigated the importance of sleep and its timing in in object

  10. Reduced hepatic tumor incidence in cyclin G1-deficient mice

    DEFF Research Database (Denmark)

    Jensen, Michael Rugaard; Factor, Valentina M; Fantozzi, Anna

    2003-01-01

    found that the p53 levels in the cyclin G1-deficient mice are 2-fold higher that in wild-type mice. Moreover, we showed that treatment of mice with the alkylating agent 1,4-bis[N,N'-di(ethylene)-phosphamide]piperazine (Dipin), followed by partial hepatectomy, decreased G1-S transition in cyclin G1-null...

  11. Effect of Yikangning on immunological function in mice

    International Nuclear Information System (INIS)

    Hou Fangyu; Xu Xiaoyi; Shi Yulu; Sheng Xuecheng; Zhao Liyan

    2001-01-01

    Objective: To investigate the effect of Yikangning oral liquid on immunological function in mice. Methods: 3 H-TdR incorporation was used to detect the lymphocyte transformation rate for Con A and LPS. Results: The drug increased the lymphocyte transformation rate in mice with lowed immunological function. Conclusion: Yikangning enhances immunological function in mice with lowered immunological function

  12. Inherent and antigen-induced airway hyperreactivity in NC mice

    Directory of Open Access Journals (Sweden)

    Tetsuto Kobayashi

    1999-01-01

    Full Text Available In order to clarify the airway physiology of NC mice, the following experiments were carried out. To investigate inherent airway reactivity, we compared tracheal reactivity to various chemical mediators in NC, BALB/c, C57BL/6 and A/J mice in vitro. NC mice showed significantly greater reactivity to acetylcholine than BALB/c and C57BL/6 mice and a reactivity comparable to that of A/J mice, which are known as high responders. Then, airway reactivity to acetylcholine was investigated in those strains in vivo. NC mice again showed comparable airway reactivity to that seen in A/J mice and a significantly greater reactivity than that seen in BALB/c and C57BL/6 mice. To investigate the effects of airway inflammation on airway reactivity to acetylcholine in vivo, NC and BALB/c mice were sensitized to and challenged with antigen. Sensitization to and challenge with antigen induced accumulation of inflammatory cells, especially eosinophils, in lung and increased airway reactivity in NC and BALB/c mice. These results indicate that NC mice exhibit inherent and antigen-induced airway hyperreactivity. Therefore, NC mice are a suitable strain to use in investigating the mechanisms underlying airway hyperreactivity and such studies will provide beneficial information for understanding the pathophysiology of asthma.

  13. Are mice eating up all the pine seeds?

    Science.gov (United States)

    Rafal Zwolak; Kerry Foresman; Elizabeth Crone; Dean Pearson; Yvette Ortega

    2008-01-01

    Wildlife, even miniscule mice, can play an important role in forest regeneration and composition by consuming seeds, seedlings, and saplings. Mice can, through sheer numbers, consume a tremendous number of seeds. We wanted to learn if deer mice could affect how ponderosa pine forests regenerate after fire.

  14. Generation of transgenic mice producing fungal xylanase in the ...

    African Journals Online (AJOL)

    DR TONUKARI NYEROVWO

    express exogenous digestive enzymes, since a single- stomached animal, such as a pig, can secret .... transgenic founder mice; 1 to15 are fifteen wild-type founder mice; M, marke; β-actin, endogenous control. (C) Identification of transgenic mice by ... 61.48±0.34%), gross energy digestibility (WT vs. TG = 68.79±0.51% vs.

  15. Inner ear dysfunction in caspase-3 deficient mice

    Directory of Open Access Journals (Sweden)

    Woo Minna

    2011-10-01

    Full Text Available Abstract Background Caspase-3 is one of the most downstream enzymes activated in the apoptotic pathway. In caspase-3 deficient mice, loss of cochlear hair cells and spiral ganglion cells coincide closely with hearing loss. In contrast with the auditory system, details of the vestibular phenotype have not been characterized. Here we report the vestibular phenotype and inner ear anatomy in the caspase-3 deficient (Casp3-/- mouse strain. Results Average ABR thresholds of Casp3-/- mice were significantly elevated (P Casp3+/- mice and Casp3+/+ mice at 3 months of age. In DPOAE testing, distortion product 2F1-F2 was significantly decreased (P Casp3-/- mice, whereas Casp3+/- and Casp3+/+ mice showed normal and comparable values to each other. Casp3-/- mice were hyperactive and exhibited circling behavior when excited. In lateral canal VOR testing, Casp3-/- mice had minimal response to any of the stimuli tested, whereas Casp3+/- mice had an intermediate response compared to Casp3+/+ mice. Inner ear anatomical and histological analysis revealed gross hypomorphism of the vestibular organs, in which the main site was the anterior semicircular canal. Hair cell numbers in the anterior- and lateral crista, and utricle were significantly smaller in Casp3-/- mice whereas the Casp3+/- and Casp3+/+ mice had normal hair cell numbers. Conclusions These results indicate that caspase-3 is essential for correct functioning of the cochlea as well as normal development and function of the vestibule.

  16. The effects of pain sensitivity behaviour on Swiss White Mice ...

    African Journals Online (AJOL)

    This study evaluates the effects of Chloroquine phosphate on pain sensation in mice considering the fact that Chloroquine as s chemotherapic agent is known for its neurotoxicity effect. The mice were divided into three groups of 10 mice each. While group 1 as the control, 2 and 3 as the test groups and group 1 received ...

  17. Dark reticular cells in the thymus of mice

    Energy Technology Data Exchange (ETDEWEB)

    Jaerplid, B [Foersvarets Forskningsanstalt, Stockholm (Sweden)

    1974-01-01

    The morphology and distribution of dark reticular cells in the thymus of normal mice, of irradiated mice, and of mice with thymic lymphoma are described. It is concluded that dark cells are epithelial reticular cells and the hypothesis is suggested that dark and light epithelial reticular cells may be different modes of expression of the same cell type. (auth)

  18. The Mice Drawer System (MDS experiment and the space endurance record-breaking mice.

    Directory of Open Access Journals (Sweden)

    Ranieri Cancedda

    Full Text Available The Italian Space Agency, in line with its scientific strategies and the National Utilization Plan for the International Space Station (ISS, contracted Thales Alenia Space Italia to design and build a spaceflight payload for rodent research on ISS: the Mice Drawer System (MDS. The payload, to be integrated inside the Space Shuttle middeck during transportation and inside the Express Rack in the ISS during experiment execution, was designed to function autonomously for more than 3 months and to involve crew only for maintenance activities. In its first mission, three wild type (Wt and three transgenic male mice over-expressing pleiotrophin under the control of a bone-specific promoter (PTN-Tg were housed in the MDS. At the time of launch, animals were 2-months old. MDS reached the ISS on board of Shuttle Discovery Flight 17A/STS-128 on August 28(th, 2009. MDS returned to Earth on November 27(th, 2009 with Shuttle Atlantis Flight ULF3/STS-129 after 91 days, performing the longest permanence of mice in space. Unfortunately, during the MDS mission, one PTN-Tg and two Wt mice died due to health status or payload-related reasons. The remaining mice showed a normal behavior throughout the experiment and appeared in excellent health conditions at landing. During the experiment, the mice health conditions and their water and food consumption were daily checked. Upon landing mice were sacrificed, blood parameters measured and tissues dissected for subsequent analysis. To obtain as much information as possible on microgravity-induced tissue modifications, we organized a Tissue Sharing Program: 20 research groups from 6 countries participated. In order to distinguish between possible effects of the MDS housing conditions and effects due to the near-zero gravity environment, a ground replica of the flight experiment was performed at the University of Genova. Control tissues were collected also from mice maintained on Earth in standard vivarium cages.

  19. Skin mites in mice (Mus musculus): high prevalence of Myobia sp. (Acari, Arachnida) in Robertsonian mice.

    Science.gov (United States)

    Sastre, Natalia; Calvete, Oriol; Martínez-Vargas, Jessica; Medarde, Nuria; Casellas, Joaquim; Altet, Laura; Sánchez, Armand; Francino, Olga; Ventura, Jacint

    2018-05-04

    Myobia sp. and Demodex sp. are two skin mites that infest mice, particularly immunodeficient or transgenic lab mice. In the present study, wild house mice from five localities from the Barcelona Roberstonian system were analysed in order to detect skin mites and compare their prevalence between standard (2n = 40) and Robertsonian mice (2n > 40). We found and identified skin mites through real-time qPCR by comparing sequences from the mitochondrial 16S rRNA and the nuclear 18S rRNA genes since no sequences are available so far using the mitochondrial gene. Fourteen positive samples were identified as Myobia musculi except for a deletion of 296 bp out to 465 bp sequenced, and one sample was identified as Demodex canis. Sampling one body site, the mite prevalence in standard and Robertsonian mice was 0 and 26%, respectively. The malfunction of the immune system elicits an overgrowth of skin mites and consequently leads to diseases such as canine demodicosis in dogs or rosacea in humans. In immunosuppressed mice, the probability of developing demodicosis is higher than in healthy mice. Since six murine toll-like receptors (TLRs) are located in four chromosomes affected by Robertsonian fusions, we cannot dismiss that differences in mite prevalence could be the consequence of the interruption of TLR function. Although ecological and/or morphological factors cannot be disregarded to explain differences in mite prevalence, the detection of translocation breakpoints in TLR genes or the analysis of TLR gene expression are needed to elucidate how Robertsonian fusions affect the immune system in mice.

  20. The Mice Drawer System (MDS) experiment and the space endurance record-breaking mice.

    Science.gov (United States)

    Cancedda, Ranieri; Liu, Yi; Ruggiu, Alessandra; Tavella, Sara; Biticchi, Roberta; Santucci, Daniela; Schwartz, Silvia; Ciparelli, Paolo; Falcetti, Giancarlo; Tenconi, Chiara; Cotronei, Vittorio; Pignataro, Salvatore

    2012-01-01

    The Italian Space Agency, in line with its scientific strategies and the National Utilization Plan for the International Space Station (ISS), contracted Thales Alenia Space Italia to design and build a spaceflight payload for rodent research on ISS: the Mice Drawer System (MDS). The payload, to be integrated inside the Space Shuttle middeck during transportation and inside the Express Rack in the ISS during experiment execution, was designed to function autonomously for more than 3 months and to involve crew only for maintenance activities. In its first mission, three wild type (Wt) and three transgenic male mice over-expressing pleiotrophin under the control of a bone-specific promoter (PTN-Tg) were housed in the MDS. At the time of launch, animals were 2-months old. MDS reached the ISS on board of Shuttle Discovery Flight 17A/STS-128 on August 28(th), 2009. MDS returned to Earth on November 27(th), 2009 with Shuttle Atlantis Flight ULF3/STS-129 after 91 days, performing the longest permanence of mice in space. Unfortunately, during the MDS mission, one PTN-Tg and two Wt mice died due to health status or payload-related reasons. The remaining mice showed a normal behavior throughout the experiment and appeared in excellent health conditions at landing. During the experiment, the mice health conditions and their water and food consumption were daily checked. Upon landing mice were sacrificed, blood parameters measured and tissues dissected for subsequent analysis. To obtain as much information as possible on microgravity-induced tissue modifications, we organized a Tissue Sharing Program: 20 research groups from 6 countries participated. In order to distinguish between possible effects of the MDS housing conditions and effects due to the near-zero gravity environment, a ground replica of the flight experiment was performed at the University of Genova. Control tissues were collected also from mice maintained on Earth in standard vivarium cages.

  1. Differential androgenesis in gamma irradiated mice

    Energy Technology Data Exchange (ETDEWEB)

    Kim, Jihyang; Yoon, Yongdal [Hanyang Univ., Seoul (Korea, Republic of); Kim, Jin Kyu [Korea Atomic Energy Research Institute, Taejon (Korea, Republic of)

    2002-07-01

    The Leydig cells of the testis account for at least 75% of the total testosterone produced in the normal adult male. Whereas the production of estrogen from androgen is catalyzed by aromatase cytochrome P450, which is found in many tissues, including gonad, brain, adipose tissue, bone, and heart. The gamma-irradiation causes the impairment of spermatogenesis and steroidogenesis in male mice. The present study was performed to analyze changes in testosterone concentrations and expression of steroidogenic enzyme of mice after whole body gamma-irradiation. Eight-week-old male ICR mice were irradiated with 6.5 or 10 Gy. At days 1, 2, 3, 4, and 5 after irradiation, testes were removed and processed for paraffin sections and isolation of mRNA. We calculated the gonad index from body and testis weight, and checked the testis volume. Hormonal analysis was performed by means of radioimmunoassay (RIA) in serum and intratesticular fluid. Semiquantitative reverse transcription polymerase chain reaction (RT-PCR) was used to evaluate the expression kinetics of the apoptotic gene and the cytochrome P450 aromatase gene after irradiation. In gamma-irradiated mice, the body weight reduced in comparison to that of the control group. Therefore, gonad indices increased. The testosterone concentrations in serum and intratesticular fluid were significantly reduced. RT- PCR data represented that the expression of Fas, Fas ligand, and aromatase cytochrome P450 showed the specific patterns against control groups. These results indicated that gamma- irradiation of adult mice induced the alteration of androgenesis and suggested that might counteract the spermatogenesis.

  2. Oral lactoferrin protects against experimental candidiasis in mice.

    Science.gov (United States)

    Velliyagounder, K; Alsaedi, W; Alabdulmohsen, W; Markowitz, K; Fine, D H

    2015-01-01

    To determine the role of human lactoferrin (hLF) in protecting the oral cavities of mice against Candida albicans infection in lactoferrin knockout (LFKO(-/-)) mice was compared to wild-type (WT) mice. We also aim to determine the protective role of hLF in LFKO(-/-) mice. Antibiotic-treated immunosuppressed mice were inoculated with C. albicans (or sham infection) by oral swab and evaluated for the severity of infection after 7 days of infection. To determine the protective role of hLF, we added 0·3% solution of hLF to the drinking water given to some of the mice. CFU count, scoring of lesions and microscopic observations were carried out to determine the severity of infection. LFKO(-/-) I mice showed a 2 log (P = 0·001) higher CFUs of C. albicans in the oral cavity compared to the WT mice infected with C. albicans (WTI). LFKO(-/-) I mice given hLF had a 3 log (P = 0·001) reduction in CFUs in the oral cavity compared to untreated LFKO(-/-) I mice. The severity of infection, observed by light microscopy, revealed that the tongue of the LFKO(-/-) I mice showed more white patches compared to WTI and LFKO(-/-) I + hLF mice. Scanning electron microscopic observations revealed that more filiform papillae were destroyed in LFKO(-/-) I mice when compared to WTI or LFKO(-/-) I + hLF mice. Human LF is important in protecting mice from oral C. albicans infection. Administered hLF may be used to prevent C. albicans infection. Human LF, a multifunctional iron-binding glycoprotein can be used as a therapeutic active ingredient in oral healthcare products against C. albicans. © 2014 The Society for Applied Microbiology.

  3. Voluntary running enhances glymphatic influx in awake behaving, young mice

    DEFF Research Database (Denmark)

    von Holstein-Rathlou, Stephanie; Petersen, Nicolas Caesar; Nedergaard, Maiken

    2018-01-01

    that exercise would also stimulate glymphatic activity in awake, young mice with higher baseline glymphatic function. Therefore, we assessed glymphatic function in young female C57BL/6J mice following five weeks voluntary wheel running and in sedentary mice. The active mice ran a mean distance of 6km daily. We...... of the cortex, but also in the middle cerebral artery territory. While glymphatic activity was higher under ketamine/xylazine anesthesia, we saw a decrease in glymphatic function during running in awake mice after five weeks of wheel running. In summary, daily running increases CSF flux in widespread areas...

  4. Inherent and antigen-induced airway hyperreactivity in NC mice

    OpenAIRE

    Tetsuto Kobayashi; Toru Miura; Tomoko Haba; Miyuki Sato; Masao Takei; Isao Serizawa

    1999-01-01

    In order to clarify the airway physiology of NC mice, the following experiments were carried out. To investigate inherent airway reactivity, we compared tracheal reactivity to various chemical mediators in NC, BALB/c, C57BL/6 and A/J mice in vitro. NC mice showed significantly greater reactivity to acetylcholine than BALB/c and C57BL/6 mice and a reactivity comparable to that of A/J mice, which are known as high responders. Then, airway reactivity to acetylcholine was investigated in those st...

  5. The pathology of facial vein blood sampling in mice

    DEFF Research Database (Denmark)

    Hansen, Ket; Harslund, Jakob le Fèvre; Bollen, Peter

    2014-01-01

    vein blood sampling. Therefore, we investigated if this technique was associated with pathological changes of the jaw region. Methods: 43 NMRI mice were subjected to facial vein blood sampling by using the lancet method during 12 months, starting at the age of 8 weeks. The mice were restrained manually......, and the tissue of the jaw was evaluated. Results: In the 23 mice, from which blood samples had been taken 2 days previously, 5 mice had no signs of gross pathological changes, whereas 12 mice had signs of minimal local subcutaneous bleeding and 6 mice had moderate local subcutaneous bleeding. No additional gross...... pathological changes were observed. In the 23 mice, from which blood samples had been taken 4 weeks earlier, no hemorrhage or signs of scar tissue formation could be observed. Histological slides are currently being processed (HE staining) and will be evaluated and discussed....

  6. Bone phenotypes of P2 receptor knockout mice

    DEFF Research Database (Denmark)

    Orriss, Isabel; Syberg, Susanne; Wang, Ning

    2011-01-01

    The action of extracellular nucleotides is mediated by ionotropic P2X receptors and G-protein coupled P2Y receptors. The human genome contains 7 P2X and 8 P2Y receptor genes. Knockout mice strains are available for most of them. As their phenotypic analysis is progressing, bone abnormalities have...... been observed in an impressive number of these mice: distinct abnormalities in P2X7-/- mice, depending on the gene targeting construct and the genetic background, decreased bone mass in P2Y1-/- mice, increased bone mass in P2Y2-/- mice, decreased bone resorption in P2Y6-/- mice, decreased bone...... formation and bone resorption in P2Y13-/- mice. These findings demonstrate the unexpected importance of extracellular nucleotide signalling in the regulation of bone metabolism via multiple P2 receptors and distinct mechanisms involving both osteoblasts and osteoclasts....

  7. Methods to measure olfactory behavior in mice.

    Science.gov (United States)

    Zou, Junhui; Wang, Wenbin; Pan, Yung-Wei; Lu, Song; Xia, Zhengui

    2015-02-02

    Mice rely on the sense of olfaction to detect food sources, recognize social and mating partners, and avoid predators. Many behaviors of mice, including learning and memory, social interaction, fear, and anxiety are closely associated with their function of olfaction, and behavior tasks designed to evaluate those brain functions may use odors as cues. Accurate assessment of olfaction is not only essential for the study of olfactory system but also critical for proper interpretation of various mouse behaviors, especially learning and memory, emotionality and affect, and sociality. Here we describe a series of behavior experiments that offer multidimensional and quantitative assessments for mouse olfactory function, including olfactory habituation, discrimination, odor preference, odor detection sensitivity, and olfactory memory, with respect to both social and nonsocial odors. Copyright © 2015 John Wiley & Sons, Inc.

  8. Radiation effects on DNA methylation in mice

    International Nuclear Information System (INIS)

    Komura, J.; Kurishita, A.; Miyamura, Y.; Ono, T.; Tawa, R.; Sakurai, H.

    1992-01-01

    Effects of ionizing radiation on DNA methylation in liver, brain and spleen were examined by high performance liquid chromatography (HPLC). The total methylated cytosine level in the genome was reduced within 8 hours after 3.8 Gy of irradiation in liver of adult mice. But no appreciable effect was observed in brain and spleen. When mice were irradiated at newborn, liver DNA revealed no change in methylated cytosine level. Even though slight effects of radiation were detected in he methylation of the c-myc and c-fos genes, they were only temporary and no long-term effects were observed. These data suggest that the effect of radiation on DNA methylation in vivo is not prevailing a DNA damage, but rather influenced much through biological parameters. (author)

  9. STUDIES ON TRANSMISSIBLE LYMPHOID LEUCEMIA OF MICE.

    Science.gov (United States)

    Furth, J; Strumia, M

    1931-04-30

    Lymphoid leucemia of the mouse is readily transmitted by intravenous inoculations. The majority of the mice inoculated successfully develop leucemic, a smaller number of them, aleucemic lymphadenosis. The data presented favor the view that leucemic and aleucemic lymphadenosis are essentially the same condition. Leucemia produced by transmission is preceded by an aleucemic stage, in which the lymph nodes and the spleen are uniformly enlarged, and the white blood count and the percentage of lymphocytes are within the normal range but immature lymphocytes are numerous in the circulating blood. Young as well as old mice may develop leucemia if leucotic material enters their circulation. Studies of transmissible leucemia favor the view that leucemia of mammals is a neoplastic disease. The basic problem of leucemia would seem to be determination of the factors that bring about a malignant transformation of lymphoid cells.

  10. Antidepressant effects of Mentha pulegium in mice

    Directory of Open Access Journals (Sweden)

    Zahra Rabiei

    2016-09-01

    Full Text Available The aim of this study is to investigate the antidepressant effects of Mentha pulegium essential oil in BALB/c mice. Six experimental groups (7 mice each were used. Forced swim test was performed 30 min after essential oil injection. In the groups receiving M. pulegium essential oil (50, 75 and 100 mg/kg, immobility duration significantly decreased compared to the control group. M. pulegium (50 and 75 mg/kg resulted in significant decrease in nitrate/nitrite content in serum compared to the control group. M. pulegium essential oil antidepressant effect that may be due to the inhibition of oxidative stress. The results showed that decrease in nitrate/nitrite content in serum and high anti-oxidant effects of M. pulegium essential oil.

  11. Hyperoxia Inhibits T Cell Activation in Mice

    Science.gov (United States)

    Hughes-Fulford, M.; Meissler, J.; Aguayo, E. T.; Globus, R.; Aguado, J.; Candelario, T.

    2013-02-01

    Background: The immune response is blunted in mice and humans in spaceflight. The effects of hyperoxia in mice alter expression of some of the same immune response genes. If these two conditions are additive, there could be an increased risk of infection in long duration missions. Immunosuppression is seen in healthy astronauts who have flown in space; however little is known about the mechanisms that cause the reduced immunity in spaceflight. Here we examine the role of oxidative stress on mice exposed to periods of high O2 levels mimicking pre-breathing protocols and extravehicular activity (EVA). To prevent decompression sickness, astronauts are exposed to elevated oxygen (hyperoxia) before and during EVA activities. Spaceflight missions may entail up to 24 hours of EVA per crewmember per week to perform construction and maintenance tasks. The effectiveness and success of these missions depends on designing EVA systems and protocols that maximize human performance and efficiency while minimizing health and safety risks for crewmembers. To our knowledge, no studies have been conducted on the immune system under 100% oxygen exposures to determine the potential for immune compromise due to prolonged and repeated EVAs. Methods: Animals were exposed to hyperoxic or control conditions for 8 hours per day over a period of 3 days, initiated 4 hours into the dark cycle (12h dark/12h light), using animal environmental control cabinets and oxygen controller (Biospherix, Lacona, NY). Experimental mice were exposed to 98-100% oxygen as a model for pre-breathing and EVA conditions, while control mice were maintained in chambers supplied with compressed air. These are ground control studies where we use real-time RTPCR (qRTPCR) to measure gene expression of the early immune gene expression during bead activation of splenocytes of normoxic and hyperoxic mice. All procedures were reviewed and approved by the IACUC at Ames Research Center. After the last 8h of hyperoxic exposure

  12. Use of Wedge Absorbers in MICE

    Energy Technology Data Exchange (ETDEWEB)

    Neuffer, D. [Fermi National Accelerator Lab. (FNAL), Batavia, IL (United States); Summers, D. [Univ. of Mississippi, Oxford, MS (United States); Mohayai, T. [Fermi National Accelerator Lab. (FNAL), Batavia, IL (United States); IIT, Chicago, IL (United States); Snopok, P. [Fermi National Accelerator Lab. (FNAL), Batavia, IL (United States); IIT, Chicago, IL (United States); Rogers, C. [Science and Technology Facilities Council (STFC), Oxford (United Kingdom). Rutherford Appleton Lab. (RAL)

    2017-03-01

    Wedge absorbers are needed to obtain longitudinal cooling in ionization cooling. They also can be used to obtain emittance exchanges between longitudinal and transverse phase space. There can be large exchanges in emittance, even with single wedges. In the present note we explore the use of wedge absorbers in the MICE experiment to obtain transverse–longitudinal emittance exchanges within present and future operational conditions. The same wedge can be used to explore “direct” and “reverse” emittance exchange dynamics, where direct indicates a configuration that reduces momentum spread and reverse is a configuration that increases momentum spread. Analytical estimated and ICOOL and G4BeamLine simulations of the exchanges at MICE parameters are presented. Large exchanges can be obtained in both reverse and direct configurations.

  13. Comments on liquid hydrogen absorbers for MICE

    International Nuclear Information System (INIS)

    Green, Michael A.

    2003-01-01

    This report describes the heat transfer problems associated with a liquid hydrogen absorber for the MICE experiment. This report describes a technique for modeling heat transfer from the outside world, to the absorber case and in its vacuum vessel, to the hydrogen and then into helium gas at 14 K. Also presented are the equation for free convection cooling of the liquid hydrogen in the absorber

  14. Nickel sensitisation in mice: a critical appraisal.

    Science.gov (United States)

    Johansen, Pål; Wäckerle-Men, Ying; Senti, Gabriela; Kündig, Thomas M

    2010-06-01

    The market release of new domestic and industrial chemical and metal products requires certain safety certification, including testing for skin sensitisation. Although various official guidelines have described how such testing is to be done, the validity of the available test models are in part dubious, for which reason regulatory agencies and research aim to further improve and generalise the models for testing of skin sensitisation. We applied a recently published murine model of nickel allergy as to test its applicability in a regulatory setting and to study and better understand the events leading to type-IV hypersensitivity. Nickel was chosen as model hapten since it induces allergic contact dermatitis with high incidence in the general population. Typically, C57BL/6 mice were sensitised and challenged by intradermal applications of nickel, and cutaneous inflammation was analysed by the mouse ear-swelling test, by histology, and by lymphocyte reactivity in vitro. Surprisingly, the study suggested that the skin reactions observed were results of irritant reactions rather than of adaptive immune responses. Non-sensitised mice responded with cutaneous inflammation and in vitro lymphocyte reactivity which were comparable with nickel-sensitised mice. Furthermore, histological examinations as well as experiments in T-cell deficient mice demonstrated that lymphocytes were not involved and that nickel caused an irritant contact dermatitis rather a true allergic type-IV contact dermatitis. The authors question the validity of the described murine model of nickel allergy. Copyright 2010 Japanese Society for Investigative Dermatology. Published by Elsevier Ireland Ltd. All rights reserved.

  15. Systemic buffers inhibit carcinogenesis in TRAMP mice.

    Science.gov (United States)

    Ibrahim-Hashim, Arig; Cornnell, Heather H; Abrahams, Dominique; Lloyd, Mark; Bui, Marilyn; Gillies, Robert J; Gatenby, Robert A

    2012-08-01

    Hypoxia and acidosis develop in in situ tumors as cellular expansion increases the diffusion distance of substrates and metabolites from blood vessels deep to the basement membrane. Prior studies of breast and cervical cancer revealed that cellular adaptation to microenvironmental hypoxia and acidosis is associated with the transition from in situ to invasive cancer. We hypothesized that decreased acidosis in intraductal tumors would alter environmental selection pressures for acid adapted phenotypes and delay or prevent evolution to invasive cancer. A total of 37 C57BL/6 TRAMP mice were randomized to a control group or to 1 of 4 treatment groups. In the latter groups 200 mM sodium bicarbonate were added to drinking water starting between ages 4 and 10 weeks. In all 18 controls prostate cancer developed that was visible on 3-dimensional ultrasound at a mean age of 13 weeks. They died within 52 weeks (median 37). When sodium bicarbonate therapy commenced before age 6 weeks in 10 mice, all reached senescence (age 76 weeks) without radiographic evidence of prostate cancer. Histological sections of the prostates in this cohort showed hyperplasia but no cancer in 70% of mice and minimal well differentiated cancer in the remainder. When therapy commenced after age 6 weeks in 9 mice, prostate cancer development was no different from that in controls. Immunohistochemical staining for carbonic anhydrase 9 in regions of ductal hyperplasia showed increased expression in controls vs the early treatment group. Regional pH perturbation in in situ tumors may be a simple, inexpensive and effective cancer prevention strategy. Copyright © 2012 American Urological Association Education and Research, Inc. Published by Elsevier Inc. All rights reserved.

  16. Radioprotectors and Tumors: Molecular Studies in Mice

    Energy Technology Data Exchange (ETDEWEB)

    Gayle Woloschak, David Grdina

    2010-03-10

    This proposal investigated effects of radiation using a set of archival tissues. Main interests of this proposal were to investigate effects of irradiation alone or in the presence or radioprotectors; to investigate these effects on different tissues; and to use/develop molecular biology techniques that would be suitable for work with archived tissues. This work resulted in several manuscripts published or in preparation. Approach for evaluation of gene copy numbers by quantitative real time PCR has been developed and we are striving to establish methods to utilize Q-RT-PCR data to evaluate genomic instability caused by irradiation(s) and accompanying treatments. References: 1. Paunesku D, Paunesku T, Wahl A, Kataoka Y, Murley J, Grdina DJ, Woloschak GE. Incidence of tissue toxicities in gamma ray and fission neutron-exposed mice treated with Amifostine. Int J Radiat Biol. 2008, 84(8):623-34. PMID: 18661379, http://informahealthcare.com/doi/full/10.1080/09553000802241762?cookieSet=1 2. Wang Q, Paunesku T and Woloschak GE. Tissue and data archives from irradiation experiments conducted at Argonne National Laboratory over a period of four decades, in press in Radiation and Environmental Biophysics. 3. Alcantara M, Paunesku D, Rademaker A, Paunesku T and Woloschak GE. A RETROSPECTIVE ANALYSIS OF TISSUE TOXICITIES IN B6CF1 MICE IRRADIATED WITH FISSION NEUTRONS OR COBALT 60 GAMMA RAYS: Gender modulates accumulation of tissue toxicities caused by low dose rate fractionated irradiation; in preparation; this document has been uploaded as STI product 4. Wang Q, Paunesku T Wanzer B and Woloschak GE. Mitochondrial gene copy number differences in different tissues of irradiated and control mice with lymphoid cancers; in preparation 5. Wang Q, Raha, S, Paunesku T and Woloschak GE. Evaluation of gene copy number differences in different tissues of irradiated and control mice; in preparation

  17. MICE data handling on the Grid

    International Nuclear Information System (INIS)

    Martyniak, J

    2014-01-01

    The international Muon Ionisation Cooling Experiment (MICE) is designed to demonstrate the principle of muon ionisation cooling for the first time, for application to a future Neutrino factory or Muon Collider. The experiment is currently under construction at the ISIS synchrotron at the Rutherford Appleton Laboratory (RAL), UK. In this paper we present a system – the Raw Data Mover, which allows us to store and distribute MICE raw data – and a framework for offline reconstruction and data management. The aim of the Raw Data Mover is to upload raw data files onto a safe tape storage as soon as the data have been written out by the DAQ system and marked as ready to be uploaded. Internal integrity of the files is verified and they are uploaded to the RAL Tier-1 Castor Storage Element (SE) and placed on two tapes for redundancy. We also make another copy at a separate disk-based SE at this stage to make it easier for users to access data quickly. Both copies are check-summed and the replicas are registered with an instance of the LCG File Catalog (LFC). On success a record with basic file properties is added to the MICE Metadata DB. The reconstruction process is triggered by new raw data records filled in by the mover system described above. Off-line reconstruction jobs for new raw files are submitted to RAL Tier-1 and the output is stored on tape. Batch reprocessing is done at multiple MICE enabled Grid sites and output files are shipped to central tape or disk storage at RAL using a custom File Transfer Controller.

  18. Ivastimul used to increase radioresistance of mice

    International Nuclear Information System (INIS)

    Rotkovska, D.; Vacek, A.; Bartonickova, A.

    1989-01-01

    A study was made of the effect of ivastimul (IS), an aqueous extract from unicellular Chlorella algae, on the radioresistance and some haemopoiesis parameters of mice exposed to 60 Co-γ-radiation. With median and absolutely lethal radiation doses, IS was shown to produce a pronounced protective effect displayed by the increased survival rate. With sublethal doses, IS elevated the postirradiation formation of endogenous colonies and restoration of bone marrow and spleen cellularity and spleen mass

  19. Mequindox Induced Genotoxicity and Carcinogenicity in Mice

    Directory of Open Access Journals (Sweden)

    Qianying Liu

    2018-04-01

    Full Text Available Mequindox (MEQ, acting as an inhibitor of deoxyribonucleic acid (DNA synthesis, is a synthetic heterocyclic N-oxides. To investigate the potential carcinogenicity of MEQ, four groups of Kun-Ming (KM mice (50 mice/sex/group were fed with diets containing MEQ (0, 25, 55, and 110 mg/kg for one and a half years. The result showed adverse effects on body weights, feed consumption, hematology, serum chemistry, organ weights, relative organ weights, and incidence of tumors during most of the study period. Treatment-related changes in hematology, serum chemistry, relative weights and histopathological examinations revealed that the hematological system, liver, kidneys, and adrenal glands, as well as the developmental and reproductive system, were the main targets after MEQ administration. Additionally, MEQ significantly increased the frequency of micronucleated normochromatic erythrocytes in bone marrow cells of mice. Furthermore, MEQ increased the incidence of tumors, including mammary fibroadenoma, breast cancer, corticosuprarenaloma, haemangiomas, hepatocarcinoma, and pulmonary adenoma. Interestingly, the higher incidence of tumors was noted in M25 mg/kg group, the lowest dietary concentration tested, which was equivalent to approximately 2.25 and 1.72 mg/kg b.w./day in females and males, respectively. It was assumed that the lower toxicity might be a reason for its higher tumor incidence in M25 mg/kg group. This finding suggests a potential relationships among the dose, general toxicity and carcinogenicity in vivo, and further study is required to reveal this relationship. In conclusion, the present study demonstrates that MEQ is a genotoxic carcinogen in KM mice.

  20. A Wedge Absorber Experiment at MICE

    Energy Technology Data Exchange (ETDEWEB)

    Neuffer, David [Fermilab; Mohayai, Tanaz [IIT, Chicago; Rogers, Chris [Rutherford; Snopok, Pavel [IIT, Chicago; Summers, Don [Mississippi U.

    2017-05-01

    Emittance exchange mediated by wedge absorbers is required for longitudinal ionization cooling and for final transverse emittance minimization for a muon collider. A wedge absorber within the MICE beam line could serve as a demonstration of the type of emittance exchange needed for 6-D cooling, including the configurations needed for muon colliders, as well as configurations for low-energy muon sources. Parameters for this test are explored in simulation and possible experimental configurations with simulated results are presented.

  1. High tidal volume ventilation in infant mice.

    Science.gov (United States)

    Cannizzaro, Vincenzo; Zosky, Graeme R; Hantos, Zoltán; Turner, Debra J; Sly, Peter D

    2008-06-30

    Infant mice were ventilated with either high tidal volume (V(T)) with zero end-expiratory pressure (HVZ), high V(T) with positive end-expiratory pressure (PEEP) (HVP), or low V(T) with PEEP. Thoracic gas volume (TGV) was determined plethysmographically and low-frequency forced oscillations were used to measure the input impedance of the respiratory system. Inflammatory cells, total protein, and cytokines in bronchoalveolar lavage fluid (BALF) and interleukin-6 (IL-6) in serum were measured as markers of pulmonary and systemic inflammatory response, respectively. Coefficients of tissue damping and tissue elastance increased in all ventilated mice, with the largest rise seen in the HVZ group where TGV rapidly decreased. BALF protein levels increased in the HVP group, whereas serum IL-6 rose in the HVZ group. PEEP keeps the lungs open, but provides high volumes to the entire lungs and induces lung injury. Compared to studies in adult and non-neonatal rodents, infant mice demonstrate a different response to similar ventilation strategies underscoring the need for age-specific animal models.

  2. Novel transcranial magnetic stimulation coil for mice

    Science.gov (United States)

    March, Stephen; Stark, Spencer; Crowther, Lawrence; Hadimani, Ravi; Jiles, David

    2014-03-01

    Transcranial magnetic stimulation (TMS) shows potential for non-invasive treatment of various neurological disorders. Significant work has been performed on the design of coils used for TMS on human subjects but few reports have been made on the design of coils for use on the brains of animals such as mice. This work is needed as TMS studies utilizing mice can allow rapid preclinical development of TMS for human disorders but the coil designs developed for use on humans are inadequate for optimal stimulation of the much smaller mouse brain. A novel TMS coil has been developed with the goal of inducing strong and focused electric fields for the stimulation of small animals such as mice. Calculations of induced electric fields were performed utilizing an MRI derived inhomogeneous model of an adult male mouse. Mechanical and thermal analysis of this new TMS helmet-coil design have also been performed at anticipated TMS operating conditions to ensure mechanical stability of the new coil and establish expected linear attraction and rotational force values. Calculated temperature increases for typical stimulation periods indicate the helmet-coil system is capable of operating within established medical standards. A prototype of the coil has been fabricated and characterization results are presented.

  3. Nicotinamide pharmacokinetics in humans and mice

    International Nuclear Information System (INIS)

    Horsman, M.R.; Hoyer, M.; Overgaard, J.; Honess, D.J.; Dennis, A.F.

    1993-01-01

    Healthy human volunteers orally ingested escalating doses of up to 6 g nicotinamide in capsule form on an empty stomach. Some side-effects were seen although these were mild and transient. HPLC analysis of blood samples showed peak plasma levels, typically within 45 min after ingestion, which were linearly dependent on dose ingested. The elimination half-life and AUC were also found to increase with drug dose, although these increases were non-linear. Pharmacokinetic studies were also performed to female CDF1 mice with C3H mammary carcinomas grown in the right rear foot. Analysis of blood and tumour samples taken from mice injected i.p. with nicotinamide doses between 100-1000 mg/kg showed similar characteristics as the human data, although the elimination half-lives were not dose-dependent. The average peak plasma concentration of 160 μg/ml measured in humans after taking 6 g of nicotinamide was equivalent to that seen in mice after injecting 171 mg/kg. Using a regrowth delay assay the enhancement of radiation damage by nicotinamide in this mouse tumour was found to be independent of drug dose from 100-1000 mg/kg, resulting in a constant 1.3-fold increase in radiation response. Doses of nicotinamide that can be tolerated clinically should therefore produce adequate enhancements of radiation damage in human tumours. (author)

  4. Radiation carcinogenesis in radiosensitive mutant Scid mice

    International Nuclear Information System (INIS)

    Ogiu, Toshiaki; Ishii-Ohba, Hiroko; Kobayashi, Shigeru; Nishimura, Mayumi; Shimada, Yoshiya; Tsuji, Hideo; Watanabe, Fumiaki; Suzuki, Fumio; Sado, Toshihiko

    2000-01-01

    The Scid mice were established as a severe combined immunodeficient mouse strain lacking both T- and B-cell functions. Scid (homozygote), its parent strain C.B-17 (wild-type) and their hybrid F1 (heterozygote) were used for analysis of the relationship between sensitivity to acute effects of ionizing radiation and radiation-tumor development. Acute effects were studied using γ-rays and LD 50(30) was found to be 4.05 Gy in Scid, 6.5 Gy in F1 and 7.2 Gy in C.B-17. When bone marrow cells were irradiated with X-rays in vitro, survival curves of C.B-17 and F1 cells showed a region of shoulder with D 0 =0.68 and 0.67 Gy, respectively, while those of Scid were of no shoulder with D 0 =0.46 Gy. Scid mice died due to tumors (most were thymic lymphoma, T/L) 20-40 weeks after irradiation with 1-3 Gy γ-rays but C.B-17 and F1 survived longer. Bone marrow transplantation was found effective to prevent the radiation T/L. FACS analysis for surface antigens of those T/L cells suggested the change of Ras oncogenes. The change of Notch 1 gene was suggested by Southern hybridization and thus a possible role of defective DNA-PK in mice alone (not in rats and humans) was suggested as well. (K.H.)

  5. Treatment of wound sepsis in irradiated mice

    International Nuclear Information System (INIS)

    Brook, I.; Elliott, T.B.

    1989-01-01

    The local and systemic effect of penicillin therapy, supplemented by immunoglobulins, and pentoxifylline on wounds infected by Staphylococcus aureus was evaluated in mice irradiated with 6.5 Gy 60 Co γ-rays. Treatment with 62.5 mg/kg penicillin-G was administered for 10 days. Numbers of bacteria were significantly reduced from 7.3 (± 0.3) to 5.3 (± 0.4) log 10 CFU/mg ± muscle in treated animals. Administration of immunoglobulin G i.v. or pentoxifylline i.p. alone, or in addition to penicillin-G, did not further reduce the number of bacteria. Increase in the dose of penicillin to 250 mg/kg decreased the number of bacteria more than 62.5 mg/kg. Bacteria were recovered from spleens and/or livers of all 13 untreated mice, and only in six of the 13 penicillin-treated mice (P<0.05). Penicillin therapy reduced the systemic spread of S. aureus. (author)

  6. Honokiol Improves Liver Steatosis in Ovariectomized Mice

    Directory of Open Access Journals (Sweden)

    Yeon-Hui Jeong

    2018-01-01

    Full Text Available Nonalcoholic fatty liver disease (NAFLD is the most common liver disease, and is associated with the development of metabolic syndrome. Postmenopausal women with estrogen deficiency are at a higher risk of progression to NAFLD. Estrogen has a protective effect against the progression of the disease. Currently, there are no safe and effective treatments for these liver diseases in postmenopausal women. Honokiol (Ho, a bioactive natural product derived from Magnolia spp, has anti-inflammatory, anti-angiogenic, and anti-oxidative properties. In our study, we investigated the beneficial effects of Ho on NAFLD in ovariectomized (OVX mice. We divided the mice into four groups, as follows: SHAM, OVX, OVX+β-estradiol (0.4 mg/kg of bodyweight, and OVX+Ho (50 mg/kg of diet. Mice were fed diets with/without Ho for 12 weeks. The bodyweight, epidermal fat, and weights of liver tissue were lower in the OVX group than in the other groups. Ho improved hepatic steatosis and reduced proinflammatory cytokine levels. Moreover, Ho markedly downregulated plasma lipid levels. Our results indicate that Ho ameliorated OVX-induced fatty liver and inflammation, as well as associated lipid metabolism. These findings suggest that Ho may be hepatoprotective against NAFLD in postmenopausal women.

  7. Zoopharmacognosy in diseased laboratory mice: conflicting evidence.

    Directory of Open Access Journals (Sweden)

    Minesh Kapadia

    Full Text Available Zoopharmacognosy denotes a constellation of learned ingestive responses that promote healing and survival of infected or poisoned animals. A similar self-medication phenomenon was reported in diseased laboratory rodents. In particular, a series of studies revealed that autoimmune MRL/lpr mice readily consume solutions paired or laced with cyclophosphamide (CY, an immunosuppressive drug that prevents inflammatory damage to internal organs. However, due to design limitations, it could not be elucidated whether such a response reflects the learned therapeutic effect of CY, or a deficit in sensory input. We presently assess the behavioural effects of prolonged consumption of CY-laced, 16% sucrose solution in a continuous choice paradigm, with tap water available ad lib. Contrary to overall expectation, MRL/lpr mice did not increase their intake of CY with disease progression. Moreover, they ingested lower doses of CY and preferred less CY-laced sucrose solution than age-matched controls. The results obtained could not confirm zoopharmacognosy in diseased MRL/lpr mice, likely due to impaired responsiveness to palatable stimulation, or attenuated survival mechanisms after prolonged inbreeding in captivity. However, by revealing the effectiveness of unrestricted drinking of drug-laced sucrose solution on behavior and immunity, the current study supports broader use of such an administration route in behavioural studies sensitive to external stressors.

  8. Mice lacking major brain gangliosides develop parkinsonism.

    Science.gov (United States)

    Wu, Gusheng; Lu, Zi-Hua; Kulkarni, Neil; Amin, Ruchi; Ledeen, Robert W

    2011-09-01

    Parkinson's disease (PD) is the second most prevalent late-onset neurodegenerative disorder that affects nearly 1% of the global population aged 65 and older. Whereas palliative treatments are in use, the goal of blocking progression of motor and cognitive disability remains unfulfilled. A better understanding of the basic pathophysiological mechanisms underlying PD would help to advance that goal. The present study provides evidence that brain ganglioside abnormality, in particular GM1, may be involved. This is based on use of the genetically altered mice with disrupted gene Galgt1 for GM2/GD2 synthase which depletes GM2/GD2 and all the gangliotetraose gangliosides that constitute the major molecular species of brain. These knockout mice show overt motor disability on aging and clear indications of motor impairment with appropriate testing at an earlier age. This disability was rectified by L-dopa administration. These mice show other characteristic symptoms of PD, including depletion of striatal dopamine (DA), loss of DA neurons of the substantia nigra pars compacta, and aggregation of alpha synuclein. These manifestations of parkinsonism were largely attenuated by administration of LIGA-20, a membrane permeable analog of GM1 that penetrates the blood brain barrier and enters living neurons. These results suggest that perturbation of intracellular mechanisms mediated by intracellular GM1 may be a contributing factor to PD.

  9. Circadian behaviour in neuroglobin deficient mice.

    Directory of Open Access Journals (Sweden)

    Christian A Hundahl

    Full Text Available Neuroglobin (Ngb, a neuron-specific oxygen-binding globin with an unknown function, has been proposed to play a key role in neuronal survival. We have previously shown Ngb to be highly expressed in the rat suprachiasmatic nucleus (SCN. The present study addresses the effect of Ngb deficiency on circadian behavior. Ngb-deficient and wild-type (wt mice were placed in running wheels and their activity rhythms, endogenous period and response to light stimuli were investigated. The effect of Ngb deficiency on the expression of Period1 (Per1 and the immediate early gene Fos was determined after light stimulation at night and the neurochemical phenotype of Ngb expressing neurons in wt mice was characterized. Loss of Ngb function had no effect on overall circadian entrainment, but resulted in a significantly larger phase delay of circadian rhythm upon light stimulation at early night. A light-induced increase in Per1, but not Fos, gene expression was observed in Ngb-deficient mice. Ngb expressing neurons which co-stored Gastrin Releasing Peptide (GRP and were innervated from the eye and the geniculo-hypothalamic tract expressed FOS after light stimulation. No PER1 expression was observed in Ngb-positive neurons. The present study demonstrates for the first time that the genetic elimination of Ngb does not affect core clock function but evokes an increased behavioural response to light concomitant with increased Per1 gene expression in the SCN at early night.

  10. Of mice and (Viking?) men: phylogeography of British and Irish house mice.

    Science.gov (United States)

    Searle, Jeremy B; Jones, Catherine S; Gündüz, Islam; Scascitelli, Moira; Jones, Eleanor P; Herman, Jeremy S; Rambau, R Victor; Noble, Leslie R; Berry, R J; Giménez, Mabel D; Jóhannesdóttir, Fríoa

    2009-01-22

    The west European subspecies of house mouse (Mus musculus domesticus) has gained much of its current widespread distribution through commensalism with humans. This means that the phylogeography of M. m. domesticus should reflect patterns of human movements. We studied restriction fragment length polymorphism (RFLP) and DNA sequence variations in mouse mitochondrial (mt) DNA throughout the British Isles (328 mice from 105 localities, including previously published data). There is a major mtDNA lineage revealed by both RFLP and sequence analyses, which is restricted to the northern and western peripheries of the British Isles, and also occurs in Norway. This distribution of the 'Orkney' lineage fits well with the sphere of influence of the Norwegian Vikings and was probably generated through inadvertent transport by them. To form viable populations, house mice would have required large human settlements such as the Norwegian Vikings founded. The other parts of the British Isles (essentially most of mainland Britain) are characterized by house mice with different mtDNA sequences, some of which are also found in Germany, and which probably reflect both Iron Age movements of people and mice and earlier development of large human settlements. MtDNA studies on house mice have the potential to reveal novel aspects of human history.

  11. Outbred CD1 mice are as suitable as inbred C57BL/6J mice in performing social tasks.

    Science.gov (United States)

    Hsieh, Lawrence S; Wen, John H; Miyares, Laura; Lombroso, Paul J; Bordey, Angélique

    2017-01-10

    Inbred mouse strains have been used preferentially for behavioral testing over outbred counterparts, even though outbred mice reflect the genetic diversity in the human population better. Here, we compare the sociability of widely available outbred CD1 mice with the commonly used inbred C57BL/6J (C57) mice in the one-chamber social interaction test and the three-chamber sociability test. In the one-chamber task, intra-strain pairs of juvenile, non-littermate, male CD1 or C57 mice display a series of social and aggressive behaviors. While CD1 and C57 pairs spend equal amount of time socializing, CD1 pairs spend significantly more time engaged in aggressive behaviors than C57 mice. In the three-chamber task, sociability of C57 mice was less dependent on acclimation paradigms than CD1 mice. Following acclimation to all three chambers, both groups of age-matched male mice spent more time in the chamber containing a stranger mouse than in the empty chamber, suggesting that CD1 mice are sociable like C57 mice. However, the observed power suggests that it is easier to achieve statistical significance with C57 than CD1 mice. Because the stranger mouse could be considered as a novel object, we assessed for a novelty effect by adding an object. CD1 mice spend more time in the chamber with a stranger mouse than that a novel object, suggesting that their preference is social in nature. Thus, outbred CD1 mice are as appropriate as inbred C57 mice for studying social behavior using either the single or the three-chamber test using a specific acclimation paradigm. Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.

  12. [Immunodepressant action of cyclophosphamide in different strains of mice].

    Science.gov (United States)

    Pevnitskiĭ, L A; Telegin, L Iu; Bol'shev, V N

    1977-04-01

    A study was made of the immunodepressive effect of cyclophosphamide (CP) on mice of 3 strains (BALB/c, CBA, and DBA/2) immunized with sheep red blood cells (SRBC). With the optimal immunizing dose of the antigen (5 X 10(8) SRBC) the most pronounced immunodepression was noted in DBA/2 mice, and with the high dose (6.2 X 10(9))--in DBA/2 and CBA mice. The CP action proved to depend on the dose of the antigen administered; in BALB/c mice a reduction in the number of the antibody-forming cells was the same with both SRBC doses, in DBA/2 mice an increase of the antigen dose led to reduction of immunode pression, and in CBA mice -- to its enhancement (with sufficiently high CP doses). Determination of the rate of oxidative CP hydroxylation by the liver microsomes of mice showed it to be comparatively low in DBA/2 and CBA mice, and much greater in BALB/c mice. It is supposed that the detected differences in the immunodepressive action of CP could be connected with different sensitivity of the target cells and (or) with the peculiarities of its metabolism in mice belonging to different strains.

  13. Lipid metabolism and body composition in Gclm(-/-) mice

    Energy Technology Data Exchange (ETDEWEB)

    Kendig, Eric L. [Department of Environmental Health, University of Cincinnati Medical Center, P.O. Box 670056, Cincinnati, OH 45267 (United States); Center for Environmental Genetics, University of Cincinnati Medical Center, P.O. Box 670056, Cincinnati, OH 45267 (United States); Chen, Ying [Department of Pharmaceutical Sciences, School of Pharmacy, University of Colorado Denver, Aurora, CO 80045 (United States); Krishan, Mansi; Johansson, Elisabet; Schneider, Scott N. [Department of Environmental Health, University of Cincinnati Medical Center, P.O. Box 670056, Cincinnati, OH 45267 (United States); Genter, Mary Beth; Nebert, Daniel W. [Department of Environmental Health, University of Cincinnati Medical Center, P.O. Box 670056, Cincinnati, OH 45267 (United States); Center for Environmental Genetics, University of Cincinnati Medical Center, P.O. Box 670056, Cincinnati, OH 45267 (United States); Shertzer, Howard G., E-mail: shertzhg@ucmail.uc.edu [Department of Environmental Health, University of Cincinnati Medical Center, P.O. Box 670056, Cincinnati, OH 45267 (United States); Center for Environmental Genetics, University of Cincinnati Medical Center, P.O. Box 670056, Cincinnati, OH 45267 (United States)

    2011-12-15

    In humans and experimental animals, high fat diets (HFD) are associated with risk factors for metabolic diseases, such as excessive weight gain and adiposity, insulin resistance and fatty liver. Mice lacking the glutamate-cysteine ligase modifier subunit gene (Gclm(-/-)) and deficient in glutathione (GSH), are resistant to HFD-mediated weight gain. Herein, we evaluated Gclm-associated regulation of energy metabolism, oxidative stress, and glucose and lipid homeostasis. C57BL/6J Gclm(-/-) mice and littermate wild-type (WT) controls received a normal diet or an HFD for 11 weeks. HFD-fed Gclm(-/-) mice did not display a decreased respiratory quotient, suggesting that they are unable to process lipid for metabolism. Although dietary energy consumption and intestinal lipid absorption were unchanged in Gclm(-/-) mice, feeding these mice an HFD did not produce excess body weight nor fat storage. Gclm(-/-) mice displayed higher basal metabolic rates resulting from higher activities of liver mitochondrial NADH-CoQ oxidoreductase, thus elevating respiration. Although Gclm(-/-) mice exhibited strong systemic and hepatic oxidative stress responses, HFD did not promote glucose intolerance or insulin resistance. Furthermore, HFD-fed Gclm(-/-) mice did not develop fatty liver, likely resulting from very low expression levels of genes encoding lipid metabolizing enzymes. We conclude that Gclm is involved in the regulation of basal metabolic rate and the metabolism of dietary lipid. Although Gclm(-/-) mice display a strong oxidative stress response, they are protected from HFD-induced excessive weight gain and adipose deposition, insulin resistance and steatosis. -- Highlights: Black-Right-Pointing-Pointer A high fat diet does not produce body weight and fat gain in Gclm(-/-) mice. Black-Right-Pointing-Pointer A high fat diet does not induce steatosis or insulin resistance in Gclm(-/-) mice. Black-Right-Pointing-Pointer Gclm(-/-) mice have high basal metabolism and mitochondrial

  14. Craniofacial Statistical Deformation Models of Wild-type mice and Crouzon mice

    DEFF Research Database (Denmark)

    Ólafsdóttir, Hildur; Darvann, Tron Andre; Ersbøll, Bjarne Kjær

    2007-01-01

    Crouzon syndrome is characterised by the premature fusion of cranial sutures and synchondroses leading to craniofacial growth disturbances. The gene causing the syndrome was discovered approximately a decade ago and recently the first mouse model of the syndrome was generated. In this study, a set...... of Micro CT scannings of the heads of wild-type (normal) mice and Crouzon mice were investigated. Statistical deformation models were built to assess the anatomical differences between the groups, as well as the within-group anatomical variation. Following the approach by Rueckert et al. we built an atlas...

  15. Cardiovascular phenotype in Smad3 deficient mice with renovascular hypertension.

    Directory of Open Access Journals (Sweden)

    Sonu Kashyap

    Full Text Available Renovascular hypertension (RVH has deleterious effects on both the kidney and the heart. TGF-β signaling through Smad3 directs tissue fibrosis in chronic injury models. In the 2-kidney 1-clip (2K1C model of RVH, employing mice on the 129 genetic background, Smad3 deficiency (KO protects the stenotic kidney (STK from development of interstitial fibrosis. However, these mice have an increased incidence of sudden cardiac death following 2K1C surgery. The purpose of this study was to characterize the cardiovascular phenotype of these mice. Renal artery stenosis (RAS was established in Wild-type (WT and Smad3 KO mice (129 genetic background by placement of a polytetrafluoroethylene cuff on the right renal artery. Mortality was 25.5% for KO mice with RAS, 4.1% for KO sham mice, 1.2% for WT with RAS, and 1.8% for WT sham mice. Myocardial tissue of mice studied at 3 days following surgery showed extensive myocyte necrosis in KO but not WT mice. Myocyte necrosis was associated with a rapid induction of Ccl2 expression, macrophage influx, and increased MMP-9 activity. At later time points, both KO and WT mice developed myocardial fibrosis. No aortic aneurysms or dissections were observed at any time point. Smad3 KO mice were backcrossed to the C57BL/6J strain and subjected to RAS. Sudden death was observed at 10-14 days following surgery in 62.5% of mice; necropsy revealed aortic dissections as the cause of death. As observed in the 129 mice, the STK of Smad3 KO mice on the C57BL/6J background did not develop significant chronic renal damage. We conclude that the cardiovascular manifestations of Smad3 deficient mice are strain-specific, with myocyte necrosis in 129 mice and aortic rupture in C57BL/6J mice. Future studies will define mechanisms underlying this strain-specific effect on the cardiovascular system.

  16. Changes in the pharmacokinetics of digoxin in polyuria in streptozotocin-induced diabetic mice and lithium carbonate-treated mice.

    Science.gov (United States)

    Ikarashi, Nobutomo; Kagami, Mai; Kobayashi, Yasushi; Ishii, Makoto; Toda, Takahiro; Ochiai, Wataru; Sugiyama, Kiyoshi

    2011-06-01

    In humans, digoxin is mainly eliminated through the kidneys unchanged, and renal clearance represents approximately 70% of the total clearance. In this study, we used the mouse models to examine digoxin pharmacokinetics in polyuria induced by diabetes mellitus and lithium carbonate (Li(2)CO(3)) administration, including mechanistic evaluation of the contribution of glomerular filtration, tubular secretion, and tubular reabsorption. After digoxin administration to streptozotocin (STZ)-induced diabetic mice, digoxin CL/F increased to approximately 2.2 times that in normal mice. After treatment with Li(2)CO(3) (0.2%) for 10 days, the CL/F increased approximately 1.1 times for normal mice and 1.6 times for STZ mice. Creatinine clearance (CLcr) and the renal mRNA expression levels of mdr1a did not differ significantly between the normal, STZ, and Li(2)CO(3)-treated mice. The urine volume of STZ mice was approximately 26 mL/day, 22 times that of normal mice. The urine volume of Li(2)CO(3)-treated mice increased approximately 7.3 times for normal mice and 2.3 times for STZ mice. These results suggest that the therapeutic effect of digoxin may be significantly reduced in the presence of polyuria either induced by diabetes mellitus or manifested as an adverse effect of Li(2)CO(3) in diabetic patients, along with increased urine volume.

  17. Effect of Jiangzhi tablet on gastrointestinal propulsive function in mice

    Science.gov (United States)

    Wang, Xiangrong; Geng, Xiuli; Zhao, Jingsheng; Fan, Lili; Zhang, Zhengchen

    2018-04-01

    This paper aims to study the effect of lipid-lowering tablets on gastric emptying and small intestinal propulsion in mice. Mice were randomly divided into control group, Digestant Pill group, Jiangzhi tablet group, middle dose and small dose, the mice gastric emptying phenolsulfonphthalein, gastric residual rate of phenol red indicator to evaluate the gastric emptying rate, residual rate of detection in mouse stomach; small intestine propulsion and selection of carbon ink as the experimental index. Effects were observed to promote the function of normal mice gastric emptying and intestine. The gastric emptying and small intestinal motor function of normal mice were all promoted by each administration group, and the effect was most obvious in small dose group. The effect of reducing blood lipid on gastrointestinal motility of mice ware obviously enhanced.

  18. Antiatherogenic effects of oleanolic acid in apolipoprotein E knockout mice

    DEFF Research Database (Denmark)

    Buus, Niels Henrik; Hansson, Nicolaj Christopher; Rodriguez-Rodriguez, Rosalia

    2011-01-01

    were investigated in vitro. Inducible nitric oxide synthase (iNOS) was visualized using immunoblotting. As opposed to WT and fluvastatin- and vehicle-treated mice, OA-fed ApoE(-/-) mice gained no weight during the treatment period. Plasma concentrations of total-cholesterol and triglyceride were...... in combination with OA (100 mg/kg/day), fluvastatin (5 mg/kg/day) or vehicle, with wild type (WT) mice serving as controls. After 8 weeks of treatment atherosclerotic plaque areas in the aortic arch and plasma lipid concentrations were determined. Vasoconstriction and relaxation of the proximal part of aorta...... not significantly reduced by OA- or fluvastatin treatment. Plaque area of vehicle-treated mice was 25%, but only 14% in OA- and 19% in fluvastatin-treated mice. As compared to WT, vasoconstriction to phenylephrine was attenuated in ApoE(-/-) mice. The NOS inhibitor asymmetric dimethylarginine (ADMA) enhanced...

  19. Impaired cutaneous wound healing in mice lacking tetranectin

    DEFF Research Database (Denmark)

    Iba, Kousuke; Hatakeyama, Naoko; Kojima, Takashi

    2009-01-01

    disruption of the tetranectin gene to elucidate the biological function of tetranectin. In this study, we showed that wound healing was markedly delayed in tetranectin-null mice compared with wild-type mice. A single full-thickness incision was made in the dorsal skin. By 14 days after the incision......, the wounds fully healed in all wild-type mice based on the macroscopic closure; in contrast, the progress of wound healing in the tetranectin null mice appeared to be impaired. In histological analysis, wounds of wild-type mice showed complete reepithelialization and healed by 14 days after the incision....... However, those of tetranectin-null mice never showed complete reepithelialization at 14 days. At 21 days after the injury, the wound healed and was covered with an epidermis. These results supported the fact that tetranectin may play a role in the wound healing process....

  20. Tumor radiation responses and tumor oxygenation in aging mice

    International Nuclear Information System (INIS)

    Rockwell, S.

    1989-01-01

    EMT6 mouse mammary tumors transplanted into aging mice are less sensitive to radiation than tumors growing in young adult animals. The experiments reported here compare the radiation dose-response curves defining the survivals of tumor cells in aging mice and in young adult mice. Cell survival curves were assessed in normal air-breathing mice and in mice asphyxiated with N 2 to produce uniform hypoxia throughout the tumors. Analyses of survival curves revealed that 41% of viable malignant cells were severely hypoxic in tumors in aging mice, while only 19% of the tumor cells in young adult animals were radiobiologically hypoxic. This did not appear to reflect anaemia in the old animals. Treatment of aging animals with a perfluorochemical emulsion plus carbogen (95% O 2 /5% CO 2 ) increased radiation response of the tumors, apparently by improving tumor oxygenation and decreasing the number of severely hypoxic, radiation resistant cells in the tumors. (author)

  1. Bex1 knock out mice show altered skeletal muscle regeneration

    International Nuclear Information System (INIS)

    Koo, Jae Hyung; Smiley, Mark A.; Lovering, Richard M.; Margolis, Frank L.

    2007-01-01

    Bex1 and Calmodulin (CaM) are upregulated during skeletal muscle regeneration. We confirm this finding and demonstrate the novel finding that they interact in a calcium-dependent manner. To study the role of Bex1 and its interaction with CaM in skeletal muscle regeneration, we generated Bex1 knock out (Bex1-KO) mice. These mice appeared to develop normally and are fertile, but displayed a functional deficit in exercise performance compared to wild type (WT) mice. After intramuscular injection of cardiotoxin, which causes extensive and reproducible myotrauma followed by recovery, regenerating muscles of Bex1-KO mice exhibited elevated and prolonged cell proliferation, as well as delayed cell differentiation, compared to WT mice. Thus, our results provide the first evidence that Bex1-KO mice show altered muscle regeneration, and allow us to propose that the interaction of Bex1 with Ca 2+ /CaM may be involved in skeletal muscle regeneration

  2. Interval timing in genetically modified mice: a simple paradigm

    OpenAIRE

    Balci, F.; Papachristos, E. B.; Gallistel, C. R.; Brunner, D.; Gibson, J.; Shumyatsky, G. P.

    2007-01-01

    We describe a behavioral screen for the quantitative study of interval timing and interval memory in mice. Mice learn to switch from a short-latency feeding station to a long-latency station when the short latency has passed without a feeding. The psychometric function is the cumulative distribution of switch latencies. Its median measures timing accuracy and its interquartile interval measures timing precision. Next, using this behavioral paradigm, we have examined mice with a gene knockout ...

  3. Travel Experience in hotels for the MICE Industry

    OpenAIRE

    Gurkina, Anastasija

    2013-01-01

    The following report is a research-oriented bachelor thesis that investigates the travel experience in the business oriented concentrated in MICE Industry. The objective of this thesis was to assess and measure the level of satisfaction of the MICE travellers in hotels, as well as to find out what are the services and aspects of the hotel that influences the most on the travel experience. The MICE travellers due to the purposes of their visit require specific services from the hotel t...

  4. Zinc metabolism in genetically obese (ob/ob) mice

    International Nuclear Information System (INIS)

    Kennedy, M.L.; Failla, M.L.

    1987-01-01

    Recent reports indicate that the concentrations and total amounts of several essential trace metals in various tissues of genetically obese rodents differ markedly from those in lean controls. In the present studies the absorption, retention and tissue distribution of zinc and constitutive levels of zinc-metallothionein (Zn-MT) in selected tissues were compared in obese (ob/ob) and lean (+/?) C57BL/6J mice. When 5-, 10- and 22-wk-old mice were administered 1.2 mumol 65 Zn by stomach tube the apparent absorption of 65 Zn by obese mice was 1.5, 2.2 and 3.9 times higher, respectively, than that in age-matched lean mice. Retention of orally administered 65 Zn after 96 h was also substantially higher in obese mice than in lean mice. To assess the possible influences of hyperphagia and intestinal hypertrophy on the enhanced apparent absorption of 65 Zn by obese mice food intake by an additional group of obese mice was restricted to that of age-matched lean controls. When actual absorption of zinc was determined according to the method of Heth and Hoekstra, groups of ad libitum--fed obese, pair-fed obese and lean mice absorbed 38, 32 and 18% of administered 65 Zn, respectively. In contrast, the rate of 65 Zn excretion 2-6 d after oral or subcutaneous administration of the metal was similar for obese and lean mice. Unrestricted and pair-fed obese mice had significantly lower percentages of carcass 65 Zn present in skin, muscle plus bone, spleen and testes and higher percentages present in liver, small intestine and adipose tissue than lean mice

  5. Reconstitution of the gastrointestinal microflora of lactobacillus-free mice.

    OpenAIRE

    Tannock, G W; Crichton, C; Welling, G W; Koopman, J P; Midtvedt, T

    1988-01-01

    A colony of mice that do not harbor lactobacilli in their digestive tracts but whose intestinal microflora is otherwise functionally similar to that of conventional animals was derived. Methods used to reconstitute the intestinal microflora of the mice included inoculation of the animals with cultures of specific microbes, noncultivable microbes attached to epithelial cells, and cecal contents from conventional mice treated with chloramphenicol. Twenty-six microflora-associated characteristic...

  6. Behavioral Characteristics of Ubiquitin-Specific Peptidase 46-Deficient Mice

    Science.gov (United States)

    Imai, Saki; Kano, Makoto; Nonoyama, Keiko; Ebihara, Shizufumi

    2013-01-01

    We have previously identified Usp46, which encodes for ubiquitin-specific peptidase 46, as a quantitative trait gene affecting the immobility time of mice in the tail suspension test (TST) and forced swimming test. The mutation that we identified was a 3-bp deletion coding for lysine (Lys 92), and mice with this mutation (MT mice), as well as Usp46 KO mice exhibited shorter TST immobility times. Behavioral pharmacology suggests that the gamma aminobutyric acid A (GABAA) receptor is involved in regulating TST immobility time. In order to understand how far Usp46 controls behavioral phenotypes, which could be related to mental disorders in humans, we subjected Usp46 MT and KO mice to multiple behavioral tests, including the open field test, ethanol preference test, ethanol-induced loss of righting reflex test, sucrose preference test, novelty-suppressed feeding test, marble burying test, and novel object recognition test. Although behavioral phenotypes of the Usp46 MT and KO mice were not always identical, deficiency of Usp46 significantly affected performance in all these tests. In the open field test, activity levels were lower in Usp46 KO mice than wild type (WT) or MT mice. Both MT and KO mice showed lower ethanol preference and shorter recovery times after ethanol administration. Compared to WT mice, Usp46 MT and KO mice exhibited decreased sucrose preference, took longer latency periods to bite pellets, and buried more marbles in the sucrose preference test, novelty-suppressed feeding test, and marble burying test, respectively. In the novel object recognition test, neither MT nor KO mice showed an increase in exploration of a new object 24 hours after training. These findings indicate that Usp46 regulates a wide range of behavioral phenotypes that might be related to human mental disorders and provides insight into the function of USP46 deubiquitinating enzyme in the neural system. PMID:23472206

  7. Behavioral characteristics of ubiquitin-specific peptidase 46-deficient mice.

    Directory of Open Access Journals (Sweden)

    Saki Imai

    Full Text Available We have previously identified Usp46, which encodes for ubiquitin-specific peptidase 46, as a quantitative trait gene affecting the immobility time of mice in the tail suspension test (TST and forced swimming test. The mutation that we identified was a 3-bp deletion coding for lysine (Lys 92, and mice with this mutation (MT mice, as well as Usp46 KO mice exhibited shorter TST immobility times. Behavioral pharmacology suggests that the gamma aminobutyric acid A (GABAA receptor is involved in regulating TST immobility time. In order to understand how far Usp46 controls behavioral phenotypes, which could be related to mental disorders in humans, we subjected Usp46 MT and KO mice to multiple behavioral tests, including the open field test, ethanol preference test, ethanol-induced loss of righting reflex test, sucrose preference test, novelty-suppressed feeding test, marble burying test, and novel object recognition test. Although behavioral phenotypes of the Usp46 MT and KO mice were not always identical, deficiency of Usp46 significantly affected performance in all these tests. In the open field test, activity levels were lower in Usp46 KO mice than wild type (WT or MT mice. Both MT and KO mice showed lower ethanol preference and shorter recovery times after ethanol administration. Compared to WT mice, Usp46 MT and KO mice exhibited decreased sucrose preference, took longer latency periods to bite pellets, and buried more marbles in the sucrose preference test, novelty-suppressed feeding test, and marble burying test, respectively. In the novel object recognition test, neither MT nor KO mice showed an increase in exploration of a new object 24 hours after training. These findings indicate that Usp46 regulates a wide range of behavioral phenotypes that might be related to human mental disorders and provides insight into the function of USP46 deubiquitinating enzyme in the neural system.

  8. The Regenerative Potential of Parietal Epithelial Cells in Adult Mice

    OpenAIRE

    Berger, Katja; Schulte, Kevin; Boor, Peter; Kuppe, Christoph; van Kuppevelt, Toin H.; Floege, Jürgen; Smeets, Bart; Moeller, Marcus J.

    2014-01-01

    Previously, we showed that some podocytes in juvenile mice are recruited from cells lining Bowman’s capsule, suggesting that parietal epithelial cells (PECs) are a progenitor cell population for podocytes. To investigate whether PECs also replenish podocytes in adult mice, PECs were genetically labeled in an irreversible fashion in 5-week-old mice. No significant increase in labeled podocytes was observed, even after 18 months. To accelerate a potential regenerative mechanism, progressive glo...

  9. Diacylglycerol lipase a knockout mice demonstrate metabolic and behavioral phenotypes similar to those of cannabinoid receptor 1 knockout mice

    Directory of Open Access Journals (Sweden)

    David R Powell

    2015-06-01

    Full Text Available After creating >4650 knockouts (KOs of independent mouse genes, we screened them by high-throughput phenotyping and found that cannabinoid receptor 1 (Cnr1 KO mice had the same lean phenotype published by others. We asked if our KOs of DAG lipase a or b (Dagla or Daglb, which catalyze biosynthesis of the endocannabinoid (EC 2-Arachidonoylglycerol (2-AG, or Napepld, which catalyzes biosynthesis of the EC anandamide, shared the lean phenotype of Cnr1 KO mice. We found that Dagla KO mice, but not Daglb or Napepld KO mice, were among the leanest of 3651 chow-fed KO lines screened. In confirmatory studies, chow- or high fat diet-fed Dagla and Cnr1 KO mice were leaner than wild type (WT littermates; when data from multiple cohorts of adult mice were combined, body fat was 47% and 45% lower in Dagla and Cnr1 KO mice, respectively, relative to WT values. In contrast, neither Daglb nor Napepld KO mice were lean. Weanling Dagla KO mice ate less than WT mice and had body weight similar to pair-fed WT mice, and adult Dagla KO mice had normal activity and VO2 levels, similar to Cnr1 KO mice. Our Dagla and Cnr1 KO mice also had low fasting insulin, triglyceride and total cholesterol levels, and after a glucose challenge had normal glucose but very low insulin levels. Dagla and Cnr1 KO mice also showed similar responses to a battery of behavioral tests. These data suggest: 1 the lean phenotype of young Dagla and Cnr1 KO mice is mainly due to hypophagia; 2 in pathways where ECs signal through Cnr1 to regulate food intake and other metabolic and behavioral phenotypes observed in Cnr1 KO mice, Dagla alone provides the 2-AG that serves as the EC signal; and 3 small molecule Dagla inhibitors with a pharmacokinetic profile similar to that of Cnr1 inverse agonists are likely to mirror the ability of these Cnr1 inverse agonists to lower body weight and improve glycemic control in obese patients with type 2 diabetes, but may also induce undesirable neuropsychiatric

  10. THC Prevents MDMA Neurotoxicity in Mice.

    Directory of Open Access Journals (Sweden)

    Clara Touriño

    2010-02-01

    Full Text Available The majority of MDMA (ecstasy recreational users also consume cannabis. Despite the rewarding effects that both drugs have, they induce several opposite pharmacological responses. MDMA causes hyperthermia, oxidative stress and neuronal damage, especially at warm ambient temperature. However, THC, the main psychoactive compound of cannabis, produces hypothermic, anti-inflammatory and antioxidant effects. Therefore, THC may have a neuroprotective effect against MDMA-induced neurotoxicity. Mice receiving a neurotoxic regimen of MDMA (20 mg/kg x 4 were pretreated with THC (3 mg/kg x 4 at room (21 degrees C and at warm (26 degrees C temperature, and body temperature, striatal glial activation and DA terminal loss were assessed. To find out the mechanisms by which THC may prevent MDMA hyperthermia and neurotoxicity, the same procedure was carried out in animals pretreated with the CB(1 receptor antagonist AM251 and the CB(2 receptor antagonist AM630, as well as in CB(1, CB(2 and CB(1/CB(2 deficient mice. THC prevented MDMA-induced-hyperthermia and glial activation in animals housed at both room and warm temperature. Surprisingly, MDMA-induced DA terminal loss was only observed in animals housed at warm but not at room temperature, and this neurotoxic effect was reversed by THC administration. However, THC did not prevent MDMA-induced hyperthermia, glial activation, and DA terminal loss in animals treated with the CB(1 receptor antagonist AM251, neither in CB(1 and CB(1/CB(2 knockout mice. On the other hand, THC prevented MDMA-induced hyperthermia and DA terminal loss, but only partially suppressed glial activation in animals treated with the CB(2 cannabinoid antagonist and in CB(2 knockout animals. Our results indicate that THC protects against MDMA neurotoxicity, and suggest that these neuroprotective actions are primarily mediated by the reduction of hyperthermia through the activation of CB(1 receptor, although CB(2 receptors may also contribute to

  11. Vocal ontogeny in neotropical singing mice (Scotinomys.

    Directory of Open Access Journals (Sweden)

    Polly Campbell

    Full Text Available Isolation calls produced by dependent young are a fundamental form of communication. For species in which vocal signals remain important to adult communication, the function and social context of vocal behavior changes dramatically with the onset of sexual maturity. The ontogenetic relationship between these distinct forms of acoustic communication is surprisingly under-studied. We conducted a detailed analysis of vocal development in sister species of Neotropical singing mice, Scotinomys teguina and S. xerampelinus. Adult singing mice are remarkable for their advertisement songs, rapidly articulated trills used in long-distance communication; the vocal behavior of pups was previously undescribed. We recorded 30 S. teguina and 15 S. xerampelinus pups daily, from birth to weaning; 23 S. teguina and 11 S. xerampelinus were recorded until sexual maturity. Like other rodent species with poikilothermic young, singing mice were highly vocal during the first weeks of life and stopped vocalizing before weaning. Production of first advertisement songs coincided with the onset of sexual maturity after a silent period of ≧2 weeks. Species differences in vocal behavior emerged early in ontogeny and notes that comprise adult song were produced from birth. However, the organization and relative abundance of distinct note types was very different between pups and adults. Notably, the structure, note repetition rate, and intra-individual repeatability of pup vocalizations did not become more adult-like with age; the highly stereotyped structure of adult song appeared de novo in the first songs of young adults. We conclude that, while the basic elements of adult song are available from birth, distinct selection pressures during maternal dependency, dispersal, and territorial establishment favor major shifts in the structure and prevalence of acoustic signals. This study provides insight into how an evolutionarily conserved form of acoustic signaling provides

  12. Liver regeneration in mice bearing a transplanted hepatoma.

    Science.gov (United States)

    Badran, A F; Moreno, F R; Echave Llanos, J M

    1984-01-01

    The hepatocyte mitotic index curve in hepatectomized hepatoma-bearing mice, rises earlier, has a greater amplitude and is less synchronized than that of normal hepatectomized mice. This indicates a stimulation (more mitosis in a shorter time period) produced by the presence of the tumors. The sinusoid litoral cells mitotic index curve in hepatectomized hepatoma-bearing mice appears earlier and is much less synchronized than that of normal hepatectomized mice. Nevertheless both curves have the same amplitude for the whole sampling period and the early stimulation is quickly compensated by lower values (apparent inhibition) appearing in the resting (light) period.

  13. Database of Physiological Parameters for Early Life Rats and Mice

    Data.gov (United States)

    U.S. Environmental Protection Agency — The Database of Physiological Parameters for Early Life Rats and Mice provides information based on scientific literature about physiological parameters. Modelers...

  14. Energy metabolism in BPH/2J genetically hypertensive mice.

    Science.gov (United States)

    Jackson, Kristy L; Nguyen-Huu, Thu-Phuc; Davern, Pamela J; Head, Geoffrey A

    2014-05-01

    Recent evidence indicates that genetic hypertension in BPH/2J mice is sympathetically mediated, but these mice also have lower body weight (BW) and elevated locomotor activity compared with BPN/3J normotensive mice, suggestive of metabolic abnormalities. The aim of the present study was to determine whether hypertension in BPH/2J mice is associated with metabolic differences. Whole-body metabolic and cardiovascular parameters were measured over 24 h by indirect calorimetry and radiotelemetry respectively, in conscious young (10-13 weeks) and older (22-23 weeks) BPH/2J, normotensive BPN/3J and C57Bl6 mice. Blood pressure (BP) was greater in BPH/2J compared with both normotensive strains at both ages (PBPH/2J compared with BPN/3J mice (PBPH/2J and normotensive mice when adjusted for activity (P>0.1) suggesting differences in this relationship are not responsible for hypertension. EchoMRI revealed that percentage body composition was comparable in BPN/3J and BPH/2J mice (P>0.1) and both strains gained weight similarly with age (P=0.3). Taken together, the present findings indicate that hypertension in BPH/2J mice does not appear to be related to altered energy metabolism.

  15. Intestinal immunity in hypopituitary dwarf mice: effects of age.

    Science.gov (United States)

    Wang, Xin; Darcy, Justin; Cai, Chuan; Jin, Junfei; Bartke, Andrzej; Cao, Deliang

    2018-03-02

    Hypopituitary dwarf mice demonstrate advantages of longevity, but little is known of their colon development and intestinal immunity. Herein we found that Ames dwarf mice have shorter colon and colonic crypts, but larger ratio of mesenteric lymph nodes (MLNs) over body weight than age-matched wild type (WT) mice. In the colonic lamina propria (cLP) of juvenile Ames mice, more inflammatory neutrophils (Ā: 0.15% vs. 0.03% in WT mice) and monocytes (Ā: 7.97% vs. 5.15%) infiltrated, and antigen presenting cells CD11c+ dendritic cells (Ā: 1.39% vs. 0.87%), CD11b+ macrophages (Ā: 3.22% vs. 0.81%) and gamma delta T (γδ T) cells (Ā: 5.56% vs. 1.35%) were increased. In adult Ames dwarf mice, adaptive immune cells, such as IL-17 producing CD4+ T helper (Th17) cells (Ā: 8.3% vs. 4.7%) were augmented. In the MLNs of Ames dwarf mice, the antigen presenting and adaptive immune cells also altered when compared to WT mice, such as a decrease of T-regulatory (Treg) cells in juvenile Ames mice (Ā: 7.7% vs.10.5%), but an increase of Th17 cells (Ā: 0.627% vs.0.093%). Taken together, these data suggest that somatotropic signaling deficiency influences colon development and intestinal immunity.

  16. MDMA reinstates cocaine-seeking behaviour in mice.

    Science.gov (United States)

    Trigo, José Manuel; Orejarena, Maria Juliana; Maldonado, Rafael; Robledo, Patricia

    2009-06-01

    MDMA effects are mediated by monoaminergic systems, which seem to play a central role in cocaine craving and relapse. CD1 mice trained to self-administer cocaine (1 mg/kg/infusion) underwent an extinction procedure in which the cues contingent with drug self-administration remained present. Mice achieving extinction were injected with MDMA (10 mg/kg), d-amphetamine (1 and 2 mg/kg) or saline and tested for reinstatement. Acute MDMA, but not d-amphetamine or saline reinstated cocaine-seeking behaviour in mice in which cocaine self-administration and contingent cues were previously extinguished. Acute MDMA can reinstate cocaine-seeking behaviour in mice.

  17. EXPERIMENTAL-INFECTION IN MICE WITH BACILLUS-LICHENIFORMIS

    DEFF Research Database (Denmark)

    Agerholm, J.S.; Jensen, H.E.; Jensen, N.E.

    1995-01-01

    The pathogenicity of Bacillus licheniformis was assessed in normal and immunodepressed BALB/c mice. The animals were challenged intravenously with 4 x 10(7) colony forming units of B, licheniformis (ATCC 14580) and both normal and immunodepressed mice were susceptible. However, the infection...... was more severe in the immunosuppressed animals. In normal mice, lesions were restricted to the liver and kidneys, while lesions also occurred in other organs of immunodepressed mice. By crossed immunoelectrophoresis it was shown that antigens of B. licheniformis are potent immunogens, and the bacteria...

  18. Effects of Social Defeat Stress on Sleep in Mice

    OpenAIRE

    Henderson, Fiona; Vialou, Vincent; El Mestikawy, Salah; Fabre, Véronique

    2017-01-01

    Stress plays a key role in the development of psychiatric disorders and has a negative impact on sleep integrity. In mice, chronic social defeat stress (CSDS) is an ethologically valid model of stress-related disorders but little is known about its effects on sleep regulation. Here, we investigated the immediate and long-term effects of 10 consecutive days of social defeat (SD) on vigilance states in C57Bl/6J male mice. Social behavior was assessed to identify susceptible mice, i.e., mice tha...

  19. Radiation sensitivity of T-lymphocytes from immunodeficient wasted mice

    International Nuclear Information System (INIS)

    Padilla, M.; Libertin, C.; Krco, C.; Woloschak, G.E.

    1990-01-01

    Mice with the autosomal recessive gene wasted (wst/wst) exhibit neurologic disorders, reduced mucosal immune responses, and abnormal DNA repair mechanisms. The wst/wst mouse has been proposed as a murine model for the human disorder ataxia telangiectasia. Experiments were designed to examine the sensitivity of T-cells from wasted mice to ionizing radiation. Results demonstrated that T-cell clones derived from wasted mice are more sensitive to the killing effects of gamma-rays than similar T-cell clones from control mice. Bulk thymocyte and splenic cell cultures demonstrated similar radiation sensitivity. Both thymic and splenic lymphocytes from wasted mice also expressed low proliferative responses to mitogenic stimulation with concanavalin A (Con A) that could not be attributed to an absence or reduction in T-cell number. However, following activation with Con A, cell cultures exhibited a marked decrease