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Assay of metronidazole in human dental pulp and dentin after a single oral dose a thesis submitted in partial fulfillment ... for the degree of Master of Science in Endodontics ... /Giovanardi, Alessandro. January 1993 (has links)
Thesis (M.S.)--University of Michigan, 1993. / Includes bibliographical references.
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The Effects of Adjunctive Metronidazole and Routine Periodontal Treatment in a Sample of Mentally Retarded Adolescents with Destructive Periodontal DiseaseShenker, Stephanie Carol 07 1900 (has links)
No description available.
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Microbiological and clinical studies on Crohn's disease effects of metronidazole and sulphasalazine /Krook, Aud. January 1980 (has links)
Thesis (doctoral)--University of Uppsala, 1980. / Includes bibliographical references (p. 41-50).
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The Preparation and use of Tc-99m metronidazole for cervical cancer imagingMdlophane, Amanda Henrietta January 2011 (has links)
Thesis(MSc(Med)Pharmacy)) -- University of Limpopo, 2011. / ABSTRACT
Introduction: Non-invasive detection of tumour hypoxia theoretically adds value to the.
outcome of treatment; however the practical aspect of using 99mTc-EC-MN in cervical cancer remains un-attempted. 99mTc-EC-MN has been used to indirectly detect hypoxia in many tumours (head and neck) and other hypoxic states such as strokes and MI. This study aims to determine the value of using this tracer in early stage cervical cancer.
Objectives: This study aimed to investigate the use of 99mTc-EC-MN to determine the degree of hypoxia in cervical cancer. The original study design was to determine whether SPECT with 99mTc-EC-MN would detect ~l'poxi~cervicalc;ancer 'lesions and compare the results with the histological report. The practice of safe handling of radiopharmaceuticals and gaining knowledge in conducting research formed part of the secondary objective of the study. Due to circumstances beyond the control of the researcher, the focus of the study changed from a clinical to a chemistry-based project.
Method development: Safety of EC-MN was tested through determination of the labelling efficiency with pertechnetate initially by ITLC-SG. Ethyl acetate, ethanol, saline and ac;etone were selected to develop 99mTc-EC-MN chromatograms to identify the system which best displays separation. Radio-ITLC displayed multiple peaks due to high residual activity in ethyl acetate- and acetone-developed scans. Saline- and ethanol-developed scans showed better separation of 99mTc-EC-MN but separation from free pertechnetate was difficult. Radio HPLC coupled with a diode array detector was used to successfully separate the labelled product, 99mTc-EC-MN from free pertechnetate, thereby achieving good radiolabelling.
Clinical application: After the relative safety of the product was established, it was injected IV in the selected patient who had early stage cervical carcinoma. Clinical examinations which included pre-operative WBC, ultrasonography of the kidneys and bladder, and chest x-rays were performed. Histological analysis was performed after surgery and gave results that were insufficient to conclude the absence or the presence of tumour hypoxia. Detection of 99mTc-EC-MN was analysed from blood-flow and -pool images, thyroid and pelvic static, SPECT, and WBS images obtained from a gamma scintillation camera. Faint hot spots consistent with low levels of free pertechnetate were detected in the salivary glands. Hot areas which paralleled the bio-distribution of the 99mTc-EC-MN were also detected in the
thyroid, liver, intestines, kidneys, and bladder. There was no tracer detection in the pelvic area.
Conclusions: Experience was gained in QC procedures and aseptic preparation of
radiopharmaceuticals, and in conducting and co-managing a chemical and clinical based research. Radiochemically related findings demonstrated that tin (II) chloride can be solubilised in water; 99mTc-EC-MN migrates with the solvent front in saline and ethanol developed ITLSG scans; and ITLC cannot sufficiently separate 99mTc-EC-MN from free pertechnetate. Successful labelling of EC-MN was confirmed by scintigraphy and showed tracer distribution that parallels those previously described. Successful labelling of EC-MN with 99mTc can be achieved up to two years after kit manufacture given appropriate storage conditions for the EC-MN. The hypoxic status of the tumour remained inconclusive; therefore the prognostic impact of 99mTc-EC-MN in cervical cancer remains unknown.
Recommendations: Product stability and potential expiry should be available for all products, even in the developmental stages and particularly for clinical trials. A simple QC method to separate 99mTc-EC-MN from free pertechnetate should be developed. Further studies are required in order to confirm the efficacy of 99mTc-EC-NM in determining tumour hypoxia in cervical cancer. If a suitable animal model is not available, patients with known cancer tissue hypoxia should be evaluated and compared with those who are non-hypoxic
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Elution of Metronidazole and Gentamicin from Polymethylmethacrylate BeadsRamos, Jose Rafaelix 16 June 2003 (has links)
Ten polymethylmethacrylate (PMMA) beads containing metronidazole (3 concentrations); gentamicin sulfate; or metronidazole and gentamicin sulfate were immersed in 5 ml of phosphate buffered saline in triplicate. Eluent was replaced at specified time intervals for 1 day (1, 3, 6, 12 and 24 hours), daily, or weekly for 21 days. Antibiotic concentrations were measured by high performance liquid chromatography. Changes in antibiotic bioactivity attributable to polymerization or co-polymerization of the antibiotics with PMMA, ethylene oxide sterilization, and storage of antibiotic-impregnated PMMA (AIPMMA) beads containing metronidazole were evaluated.
Antibiotic elution patterns were similar for all groups. Day-1 elution for groups containing either metronidazole (3 concentrations) or gentamicin represented a mean 63% to 66% and 79% respectively of the 21-day total elution. Approximately 50% of the day-1 elution occurred during the first hour. The elution of metronidazole was dose-dependent. There was no significant difference in the total amount of antibiotic eluted from groups that had the saline changed daily versus weekly. The elution of metronidazole (day 3-21) and gentamicin (all days) was significantly greater when metronidazole and gentamicin were combined (p<0.05). Polymerization of PMMA was delayed in groups containing metronidazole. Neither polymerization nor co-polymerization of metronidazole and gentamicin with PMMA, gas-sterilization, or 2-month storage of beads containing metronidazole significantly affected antimicrobial bioactivity.
Metronidazole elutes from PMMA. The frequency at which the saline was changed did not affect the rate of antibiotic elution. Co-polymerization of metronidazole and gentamicin sulfate in PMMA resulted in increased rates of elution. Intra-operative preparation of metronidazole-impregnated PMMA beads is not practical. However, prefabrication of metronidazole or metronidazole-gentamicin beads, gas-sterilization and storage for up to 2 months should not affect the efficacy of either antibiotic. The local delivery of biologically active metronidazole and gentamicin by elution from PMMA is feasible. / Master of Science
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Using zebrafish to develop a precise model of cone photoreceptor ablation and regenerationFraser, Irene Brittany Morgan Unknown Date
No description available.
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The effects of metronidazole and tinidazole on trichomonas vaginalis by using in-vitro and in vivo methods /Pornthip Prasomsiti, Pramualmal Sucharit, January 1978 (has links) (PDF)
Thesis (M.Sc. (Tropical Medicine))--Mahidol University, 1978.
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The development and assessment of a fixed dose combination tablet of Ranitidine and MetronidazoleKing'ori, Loti David 07 April 2011 (has links)
The oral route of drug administration is convenient since it is acceptable to most patients and the manufacturing processes used to produce tablets and capsules are relatively simple when compared to those used to manufacture other types of dosage forms. Metronidazole (MTZ) and Ranitidine (RTD) have been used in combination, as part of triple therapy for the treatment of ulcers. However the use of large numbers of tablets and long duration of therapy makes adherence to drug treatment challenging for patients. Therefore the formulation of a fixed dose combination (FDC) of MTZ and RTD may improve patient adherence to therapy and consequently may reduce morbidity and mortality due to ulcers. A stability indicating HPLC method for the simultaneous analysis of MTZ and RTD was developed and validated according to the International Conference on Harmonization (ICH) guidelines. The method was sensitive, selective, precise, accurate and linear.Preformulation studies were performed on the active pharmaceutical ingredients (API) alone and in combination with potential excipients. Differential scanning calorimetry (DSC) studies revealed a potential interaction between MTZ and RTD, however the interaction was not apparent following IR analysis of the same samples. DSC analyses of the API in combination with potential excipients revealed that the compounds were compatible with most materials with the exception of a binary mixture of RTD and Dibasic calcium phosphate (DCP) that exhibited a potential interaction. Thermal gravimetric analysis (TGA) of MTZ and RTD revealed that both compounds exhibited thermal stability. The Carrs Index (CI) and Hausner Ratio (HR) values of MTZ and RTD indicated that both compounds exhibited poor flow and compressibility properties, whereas the CI and HR values for (Microcrystalline cellulose) MCC and DCP indicated better flowability and compressibility characteristics.Direct compression and wet granulation processes were assessed to identify a suitable method of manufacture of FDC tablets of MTZ and RTD. The blends were evaluated using bulk and tapped density and the resultant tablets were evaluated for weight uniformity, crushing strength, tensile strength and disintegration time. The wet granulation method of manufacture produced tablets that showed acceptable pharmacotechnical properties: this approach was therefore used as the method of manufacture of FDC tablets of MTZ and RTD. Tablet formulations comprised of API, viz. MTZ and RTD and different compositions of MCC, DCP, Sodium starch glycolate (SSG) and Croscarmellose sodium (CCS), were manufactured in order to screen for an appropriate diluent and disintegrant composition for use in response surface studies. Assays of tablet content and in vitro drug release were undertaken using the validated HPLC method. Tablets in which MCC and CCS were used appeared to produce better assay and dissolution results as compared to those manufactured using DCP and SSG. Consequently a formulation comprised of MCC and CCS was selected and used in studies in which the effect(s) of level two formulation and composition changes as described in the Scale and Post Approval Changes for Immediate Release (SUPAC-IR) Guidelines on tablet disintegration and in vitro release were assessed. A Box-Behnken statistical design was used for the investigation of the effect of input factors, viz. CCS, (Polyvinyl pyrollidone K30) PVP-K30 and magnesium stearate on measured responses, viz. disintegration time and percent drug release in 10 minutes (Q10). CCS appeared to have an inverse linear relationship on disintegration time and a linear relationship with the Q10 for MTZ and RTD, whereas PVP-K30 and magnesium stearate appeared to have an antagonistic effect on the measured responses. Furthermore CCS and magnesium stearate exhibited an interaction that had an agonistic effect on the Q10 value for RTD. A numerical optimization approach was used to predict a formulation composition that would produce tablets that exhibited a disintegration time and Q10 values for MTZ and RTD that fell within the constraints set in our laboratory. The resultant model was found to be accurate and had a percent prediction error of < 5% for all measured response variables.FDC tablets of MTZ and RTD have been successfully produced. The disintegration of the tablet and dissolution of the API were within compendial specifications and the tablets are of suitable quality and have the potential to be further investigated to reduce the pill burden in the treatment of ulcers.
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In vitro resistance of human periodontal anaerobic bacterial pathogens to tinidazole versus metronidazoleLin, Daniel Liwei January 2019 (has links)
Objectives: Most bacterial species implicated as pathogens in human periodontitis are anaerobic in their metabolism. Systemic administration of metronidazole, an antibiotic specifically active against anaerobic bacteria, has been shown in multiple clinical trials to be beneficial in enhancing periodontal therapeutic outcomes beyond that attained by conventional mechanically-based forms of periodontal therapy alone, in large part by the drug inducing better reductions of major anaerobic pathogens in periodontal pockets. However, systemic metronidazole regimens in the treatment of periodontitis require multiple patient-administered drug doses per day, which may compromise treatment benefits in patients less compliant with prescribed oral drug consumption schedules. Tinidazole, a second-generation 2-methyl-5-nitroimidazole class antibiotic similar to metronidazole, also possesses marked antibacterial activity against anaerobic bacteria, and exhibits pharmacokinetic properties that enable its bioavailability with only a once-a-day oral drug dose, which may be an advantage for use in periodontitis patients unable to comply with more frequent drug dosing regimens. Little comparative data is available assessing the potential antimicrobial effects of tinidazole, as compared to metronidazole, against anaerobic periodontal pathogens, particularly “wild-type” clinical strains isolated from severely-diseased human periodontal pockets. As a result, this study tested fresh clinical subgingival isolates of selected anaerobic red and orange complex periodontal pathogens for their in vitro susceptibility to tinidazole, metronidazole, and three other antibiotics frequently employed in periodontal therapy. Methods: Paper point subgingival plaque biofilm specimens were removed from 31 adults with severe periodontitis, and transported in VMGA III medium from variousUnited States private periodontal practices to the Oral Microbiology Testing Service Laboratory at Temple University School of Dentistry. Within 24 hours, the samples were serial diluted and plated onto enriched Brucella blood agar plates with either no antimicrobials added, or supplemented with either tinidazole at 16 mg/L, metronidazole at 16 mg/L, doxycycline at 4 mg/L, amoxicillin at 8 mg/L, or clindamycin at 4 mg/L, which represent recognized non-susceptible drug breakpoint concentrations for each of the antibiotics. After incubation at 37°C for 7 days in an 85% N2-10% H2-5% CO2 anaerobic atmosphere, all plates were examined with established phenotypic criteria for selected anaerobic red and orange complex periodontal pathogens, including Porphyromonas gingivalis, Tannerella forsythia, Prevotella intermedia/nigrescens, Parvimonas micra, and Fusobacterium nucleatum group species. In vitro antibiotic resistance was noted when any of the test bacterial species displayed growth on one or more of the antibiotic-supplemented enriched Brucella blood agar plates. A paired t-test compared mean total subgingival proportions of the evaluated anaerobic red and orange complex periodontal pathogens per patient which were resistant in vitro to non- susceptible drug threshold concentrations of tinidazole as compared to metronidazole, as well as to doxycycline, amoxicillin, and clindamycin, with a P-value of < 0.05 required for statistical significance. Results: The study patients yielded an average 25.8% per patient of total subgingival proportions of the selected anaerobic red and orange complex periodontal pathogens. Among these species, P. micra was isolated from all (100%) study patients, and P. intermedia/nigrescens and F. nucleatum from 93.5% and 90.3% patients, respectively, with mean subgingival proportions of these species in positive patientsranging from 1.8% to 9.7%. T. forsythia at mean subgingival levels of 1.8% was recovered from 54.8% of the patients, whereas subgingival P. gingivalis averaged 9.1% in 5 (16.1%) patients. Tinidazole and metronidazole at 16 mg/L threshold concentrations inhibited in vitro growth of all test periodontal pathogens, except for a tinidazole-resistant strain of P. intermedia/nigrescens in one patient that was additionally resistant in vitro to doxycycline, amoxicillin and clindamycin. No statistically significant differences were found between tinidazole and metronidazole in mean total subgingival proportions of anaerobic red and orange complex periodontal pathogens per patient exhibiting in vitro resistance to a 16 mg/L drug concentration (P = 0.327, paired t-test). However, significantly greater total subgingival proportions of anaerobic red and orange complex periodontal pathogens per patient were resistant in vitro to breakpoint concentrations of either doxycycline, amoxicillin, or clindamycin, as compared to tinidazole or metronidazole (all P-values < 0.006, paired t-test). Conclusions: Tinidazole performed in vitro similar to metronidazole, but significantly better than doxycycline, amoxicillin, or clindamycin, in antimicrobial activity against freshly-isolated clinical strains of human subgingival anaerobic red and orange complex periodontal pathogens. As a result of its similar spectrum of antimicrobial inhibition against anaerobic bacteria, and its more convenient once-a-day oral drug dosing properties, tinidazole may be prescribed for clinical systemic use in place of metronidazole in severe human periodontitis treatment regimens where patient compliance with multiple dose per day systemic drug consumption is anticipated to be poor or difficult to attain. / Oral Biology
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Avaliação de biofilmes patogênicos: efeito de um sistema de liberação contendo metronidazol / Evaluation of pathogenic biofilms: effect of a release system containing metronidazoleRé, Ana Carolina dos Santos 31 March 2017 (has links)
O perfil de liberação e o efeito de um sistema de liberação prolongada contendo metronidazol, antimicrobiano prescrevido para o tratamento da periodontite, foram avaliados na presença de biofilmes supra e subgengivais, representados respectivamente pelas bactérias Streptococcus mutans e Porphyromonas gingivalis. Os biofilmes foram crescidos e expostos ao sistema de liberação prolongada contendo metronidazol (MDZ) ou ao controle de veículo da formulação (CV), composto de monoglicerídeos e monoesterato de sorbitano. Biofilmes não tratados foram utilizados como controle negativo (CN). Os biofilmes e os meios de cultura de S. mutans foram coletados após a primeira exposição aos tratamentos nos tempos 24, 48, 72 e 96 horas enquanto para biofilmes de P. gingivalis os tempos foram 24, 48 e 72 horas. Após coleta, os biofilmes foram analisados em relação à quantificação de fármaco e viabilidade bacteriana (biofilmes de S. mutans: n=3; biofilmes de P. gingivalis: n=6). Biofilmes de S. mutans também foram avaliados em relação à acidogenicidade. Nos biofilmes supragengivais, a quantificação de MDZ nas primeiras 24 horas foi de 7% em relação à concentração inicial de fármaco na formulação, permanecendo em torno de 1% para os demais tempos. O teor de MDZ liberado da formulação reduziu a viabilidade bacteriana no tempo 24 horas e diminuiu a acidogenicidade dos biofilmes por 48 horas em relação aos grupos CV e NC (p<0,05). Já para os biofilmes subgengivais, 19% de MDZ foram liberados da formulação nas primeiras 24 horas e 5% do fármaco foram quantificados nas análises dos demais tempos. O antimicrobiano liberado reduziu a viabilidade bacteriana em todos os tempos em relação à CV e NC (p<0,05), não sendo diferente estatisticamente entre si (p>0,05). O grupo CV apresentou menor viabilidade bacteriana se comparado ao grupo CN (p<0,05), mas maior viabilidade em comparação ao grupo MDZ em todos os tempos (p<0,05). De uma forma geral, o sistema de liberação prolongada proposto neste estudo foi capaz de inviabilizar a proliferação de biofilmes de P. gingivalis e de desestabilizar biofilmes de S. mutans. Além disso, os microambientes originados pelos biofilmes interferiram na cinética de liberação do metronidazol, diminuindo sua disponibilidade biológica. Assim, considerando a continuidade do biofilme sub e supragengival, torna-se interessante aprofundar os estudos sobre formulações que possam inibir biofilmes subgengivais ao mesmo tempo em que desestabilizam biofilmes supragengivais, evitando a rápida recolonização dos nichos periodontais tratados. Em acréscimo, a possibilidade de estudar parâmetros operacionais de desenvolvimento da formulação farmacêutica utilizando-se modelos de biofilmes patogênicos pode ser considerada em futuros estudos / The drug release profile and the effect of a controlled release system containing metronidazole, an antibiotic prescribed for the treatment of periodontitis, were evaluated in the presence of supra and subgingival biofilms, represented respectively by the bacteria - Streptococcus mutans and Porphyromonas gingivalis. The biofilms were grown and exposed to the controlled release system containing metronidazole (MDZ) as well as vehicle control (VC) of the formulation containing monoglycerides and sorbitan monostearate. Untreated biofilms were used as negative control (NC). The biofilms and culture media of S. mutans were collected after the first exposure to the treatments at times 24, 48, 72 and 96 hours while for P. gingivalis biofilms, the times were 24, 48 and 72 hours. After collection, biofilms were analyzed for drug quantification and bacterial viability (S. mutans biofilms: n=3; P. gingivalis biofilms: n=6). Biofilms of S. mutans were also evaluated for acidogenicity. In the supragingival biofilms, the MDZ quantification in the first 24 hours was 7% in relation to the initial concentration of drug in the formulation, remaining around 1% for the remaining times. The amount of MDZ released from the formulation reduced the bacterial viability in the 24 hour and decreased the acidogenicity of the biofilms by 48 hours in relation to the VC and NC groups (p <0.05). As for subgingival biofilms, 19% of MDZ was released from the formulation in the first 24 hours and 5% of the drug was quantified in the other analyses. The MDZ released reduced bacterial viability in relation to VC and NC (p <0.05), and was not statistically different at all sampling times studied (p> 0.05). The VC group presented lower number of viable bacteria than NC (p <0.05), however, it was higher when compared to the MDZ-treated group at all sampling times studied (p <0.05). In general, the controlled release system proposed in this study was able to prevent the proliferation of P. gingivalis biofilms and to destabilize S. mutans biofilms. In addition, microenvironments caused by biofilms interfered with the release kinetics of metronidazole, reducing its bioavailability. Thus, considering the continuity of the sub and supragingival biofilms, it is imperative to deepen the studies on formulations that can inhibit the formation of subgingival biofilms while destabilizing supragingival biofilms, thereby avoiding the rapid recolonization of the treated periodontal niches. In addition, the possibility of studying operational parameters for the development of pharmaceutical formulations using models of pathogenic biofilms can be considered in future studies
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