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1
Morin, Jean-Paul. "Etude des mécanismes de l'action nephrotoxique de la gentamicine." Rouen, 1987. http://www.theses.fr/1987ROUES046.
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La gentamicine s'accumule sélectivement dans les lysosomes des cellules tubulaires proximales de rein de rat ou de lapin, au sein desquels elle provoque une phospholipidose. L'étude morphométrique de la cellule tubulaire proximale en ultrastructure a révélé que la gentamicine provoque une augmentation de la densité de lysosomes par unité de volume cellulaire, et une augmentation de la taille de ces organites, parallèlement à la survenue d'une surcharge par des corps myéloïdes. L'étude biochimique du cortex rénal a révélé que la gentamicine provoque une diminution de l'activité des phospholipases A1, A2 et C et de la sphingomyélinase ayant pour conséquence la survenue de la phospholipidose. L'activité de la cathepsine B, le turnover des phosphoinositides membranaires et le transport cellulaire du calcium sont aussi diminués lors du traitement par la gentamicine. L'étude fonctionnelle a révélé que la gentamicine provoque l'apparition d'une polyurie, d'une élévation de l'excrétion urinaire de N-acetyl-β-D-glucosaminidase et de calcium, d'une forte diminution de l'excrétion urinaire d'AMP cyclique et peu de modifications de l'excrétion urinaire de sodium, de potassium, de magnésium et de phosphore. L'étude de l'éventuelle modulation de la toxicité rénale de la gentamicine par l'administration conjointe de Muzolimine* (un diurétique de l'anse), de Perindopril* (un inhibiteur de l'enzyme de conversion) ou d'une surcharge alimentaire en calcium a montré que : - la surcharge calcique protège contre l'atteinte fonctionnelle du rein. - L'administration conjointe d'un diurétique de l'anse ne modifie pas l'atteinte rénale induite par la seule gentamicine. - L'inhibition du système rénine angiotensine potentialise la toxicité rénale de la gentamicine. Les deux cibles privilégiées de la toxicité rénale de la gentamicine sont l'appareil lysosomal d'une part et d'autre part la membrane péricellulaire du pôle apical des cellules tubulaires proximales. Le rôle de l'obstruction tubulaire dans le développement de l'insuffisance rénale aiguë provoquée par la gentamicine est discutée.
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LeBrun, Michel. "Signalisation intracellulaire et mécanismes de néphrotoxicité de la gentamicine." Thesis, National Library of Canada = Bibliothèque nationale du Canada, 2001. http://www.collectionscanada.ca/obj/s4/f2/dsk3/ftp04/NQ60775.pdf.
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Robert, Nathalie. "La néphrotoxicité de la gentamicine et les intéractions médicamenteuses." Paris 5, 1992. http://www.theses.fr/1992PA05P086.
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Morin, Jean-Paul. "Etude des mécanismes de l'action néphrotoxique de la gentamicine." Grenoble 2 : ANRT, 1987. http://catalogue.bnf.fr/ark:/12148/cb37608163g.
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Benkirane, Abdelkrim. "Emergence de "Staphylococcus aureus" résistants à la méticilline et sensibles à la gentamicine en milieu hospitalier entre 1993 et 1995 : aspects microbiologiques et épidémiologiques." Paris 5, 1997. http://www.theses.fr/1997PA05P070.
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Mugabe, Clement, and Abdelwahab Omri. "La gentamicine sous la forme liposomale : aspects technologique et microbiologique." Acfas-Sudbury, 2005. https://zone.biblio.laurentian.ca/dspace/handle/10219/63.
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Poirier, André. "Influence de l'infection rénale sur la néphrotoxicité de la gentamicine." Master's thesis, Université Laval, 1985. http://hdl.handle.net/20.500.11794/33572.
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Dans le but d'évaluer l'influence de l'infection rénale sur la toxicité de la gentamicine, une pyélonéphrite expérimentale à Escherichia coli est induite chez les rats. Plusieurs groupes d'animaux : infectés, traités ou infectés et traités ont été étudiés. Deux traitements à la gentamicine furent institués: 1- 10 mg/kg Q8H et 2- 30 mg/kg Q8H, pendant 3 jours. Plusieurs paramètres de toxicité rénale ont été analysés soient : la diurèse, l'osmolalité urinaire, la protéinurie, la B-galactosurie et Y-glutamyltransférase. Que ce soit a basse ou à haute dose, l'infection rénale semble potentialiser la néphrotoxicité de la gentamicine<br>Montréal Trigonix inc. 2018
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SARTRE, JACQUES. "Determination de l'effet bactericide, sur des souches de staphylocoques, des glycopeptides associes a une fluoroquinolone ou a un aminoside, par une methode cinetique, au moyen de l'ensemenceur spiral." Lyon 1, 1990. http://www.theses.fr/1990LYO1M317.
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Brunschwig, Caroline. "Entérocoques résistants aux béta-lactamines : vitesses de bactéricidie d'associations d'antibiotiques : étude in vitro." Montpellier 1, 1991. http://www.theses.fr/1991MON11186.
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Bunetel, Laurence. "Ciments et antibiotique : étude expérimentale de la diffusion." Rennes 1, 1988. http://www.theses.fr/1988REN1B006.
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Muhammed, Salih Muhsin. "Nanoémulsion multiple autoémulsionnable pour délivrance de médicaments polaires : applications à la gentamicine." Paris 5, 2008. http://www.theses.fr/2008PA05P642.
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La gentamicine (GM) est un médicament hydrophile polaire référence de la classe III BCS, reconnu comme non absorbé par voie orale. L’objectif du présent travail est de formuler un véhicule capable de permettre l’absorption orale de la GM. Une nouvelle forme galénique Nanoémulsion Multiple H/L/H Autoémulsionnable a été mise au point. Cette formule est obtenue par autoémulsification d’une microémulsion H/L primaire, composée d’huile (triglycérides à chaîne moyenne), de surfactifs (polysorbate85 et Labrasol®) et d’une phase hydrophile (eau). La GM est incorporée dans la phase interne aqueuse. L’émulsion finale est formée spontanément par l’addition de la microémulsion H/L primaire dans l’eau (ratio1-2). Les diagrammes de phases pseudo-ternaires ont été établis pour déterminer la zone isotrope et limpide de la microémulsion H/L. Les préparations ont été caractérisées par différentes méthodes ; comme l’aspect macroscopique, la viscosité, la taille, la forme et la charge de particules, en utilisant la spectroscopie à corrélation de photon, la diffraction laser et la microscopie électronique à transmission. Les études in vivo ont été conduites sur le modèle de rat éveillé. Les concentrations sanguines de GM ont été déterminées par HPLC-spectroscopie de masse. Les résultats ont montré une biodisponibilité élevée avec un profil d’absorption prolongé permettant d’envisager une administration orale. La nouvelle formulation a été dénommée Multiple Self Emulsifying Nanoemulsion for Polar Drugs Delivery MSEN-PDD®<br>The aminoglycoside gentamicin sulphate is a representative orally non absorbable hydrophilic polar drug corresponding to class III BCS. This work proposes a new lipid-based formulation designed to improve oral absorption of class III drugs. The formulation is a Multiple w/o/w Self-Emulsifying Nanoemulsion obtained by efficient spontaneous emulsification of a former w/o microemulsion consisting of Medium Chains Triglycerides (MCT) as oil, polysorbat85/Labrasol® as surfactants and gentamicin was incorporated in the aqueous internal phase of former w/o microemulsions. Pseudoternary phase diagrams were established to determine w/o microemulsions zones. Formulations were characterized; physical properties like macroscopic aspects, viscosity also particle size, form and charge were studied using photon correlation spectroscopy (PCS), laser diffraction, transmission electron microscopy (TEM) and other techniques. Oral absorption studies were conducted in vivo using conscious rat model. Plasma levels were quantified by HPLC-Mass Spectrometry to study oral absorption bioavailability. After administration the results show high bioavailability and the absorption shows sustained release profile which permit oral administration. The new formulation was named Multiple Self Emulsifying Nanoemulsion for Polar Drugs Delivery MSEN-PDD®
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Ouedraogo, Moustapha. "Développement d'un implant biodégradable à base de gentamicine et de monoléine destiné au traitement des ostéomyélites chroniques." Doctoral thesis, Universite Libre de Bruxelles, 2008. http://hdl.handle.net/2013/ULB-DIPOT:oai:dipot.ulb.ac.be:2013/210537.
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L’ostéomyélite chronique est une infection chronique du tissu osseux et de la moelle. C’est une infection grave du fait de sa localisation au sein d’un tissu profond, de la complexité de sa prise en charge thérapeutique et de la mise en jeu du pronostic fonctionnel. L’incidence de l’ostéomyélite chronique est accrue sur certains terrains (drépanocytose, diabète, et polyarthrite rhumatoïde entre autres). Son traitement classique repose sur un curettage chirurgical associé à une antibiothérapie par voie générale durant au moins 6 semaines. Ce traitement est marqué le plus souvent par des échecs du fait de la difficulté de faire parvenir des antibiotiques à doses efficaces et de manière prolongée ou continue au niveau de l'os infecté.<p>\<br>Doctorat en Sciences biomédicales et pharmaceutiques<br>info:eu-repo/semantics/nonPublished
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Boisson, Matthieu. "Étude de la nébulisation de deux antibiotiques en ventilation mécanique." Thesis, Poitiers, 2016. http://www.theses.fr/2016POIT1403/document.
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Les pneumopathies acquises sous ventilation mécanique (PAVM) sont responsables d'une mortalité élevée. La nébulisation d'antibiotiques permet d'améliorer l'efficacité de leur traitement. Pour autant, aucune donnée pharmacocinétique portant sur la colistine et la gentamicine ne permet de recommander un schéma posologique particulier.Nous avons comparé les propriétés pharmacocinétiques plasmatique et intra-pulmonaire de la colistine (administrée sous forme de prodrogue, le colistiméthate sodique ou CMS) et de la gentamicine selon le mode d'administration (nébulisation ou perfusion intraveineuse) chez des patients de réanimation présentant une PAVM.Les concentrations intra-pulmonaires de colistine et de gentamicine étaient, respectivement, de 10 à 40 et 50 à 70 fois supérieures, après nébulisation, à celles retrouvées après administration d'une même dose par voie intraveineuse. La nébulisation permettrait également de limiter le risque de toxicité systémique avec une biodisponibilité inférieure à 10%.En assurant de fortes concentrations intra-pulmonaires et un faible passage systémique, la nébulisation de CMS et de gentamicine pourrait être une bonne alternative à leur administration intraveineuse dans le traitement des PAVM<br>Ventilator-associated pneumonia (VAP) is associated with high mortality. Nebulization of antibiotics improves outcome of patient with VAP. However, pharmacokinetic data concerning colistin and gentamicin allowing for optimal dosing regimen recommendation are lacking.We compared systemic and pulmonary concentrations of colistin (administered as an inactive prodrug, colistin methanesulfonate or CMS) and gentamicin according to the route of administration (nebulization and intravenous infusion) in critically ill patients with VAP.Intra-pulmonary concentrations of colistin and gentamicin were 10 to 40-fold and 50 to 70-fold much higher after nebulization than after the same dose by intravenous route, respectively. Nebulization has also the theoretical potential advantage to improve patients' safety in relation to the colistin biodisponibility lower than 10%.With high intra-pulmonary concentrations and very low systemic absorption, CMS and gentamicin nebulization may be good alternatives to intravenous infusion for VAP treatment
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FRANCINEAU, PHILIPPE. "Consequences cliniques et microbiologiques du changement d'un aminoside en premiere intention dans un service de neonatologie : surveillance epidemiologique comparative de deux cohortes." Clermont-Ferrand 1, 1992. http://www.theses.fr/1992CLF13814.
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Rouas, Caroline. "Etude des mécanismes mis en jeu lors d'une exposition à l'uranium appauvri sur le système de détoxification in vivo et in vitro." Paris 11, 2010. http://www.theses.fr/2010PA114835.
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Le but de cette thèse est d'explorer, in vivo et in vitro, l'action de l'uranium (U) sur les protagonistes du système de détoxification de l'organisme, le rein et le foie. Pour mimer une contamination chronique à une dose environnementale, le modèle in vivo est basé sur une exposition de 9 mois de rats à l'U. In vivo, nos résultats montrent que la contamination à l'U n'induit ni une néphrotoxicité ni une sensibilité du rein à exacerber une néphrotoxicité due à la gentamicine. Concernant le foie, l'U induit des modifications de l'expression d’enzymes du métabolisme des xénobiotiques (EMXs). Ces modifications ne sont responsables de perturbations du métabolisme du paracétamol que lorsqu’il est administré à une dose hépatotoxique. Les résultats in vitro (1)suggèrent que les modifications des EMXs proviennent d'un effet indirect de l'U et (2)souligne le potentiel cytotoxique de l'U ainsi que sa présence dans les cellules (cytoplasme et noyau) sous forme soluble et/ou précipitée<br>The aim of this work is to study the effects of a uranium (U) exposure on organs involved in the detoxification: the kidney and the liver (and notably the xenobiotics metabolizing enzymes (XME)). In order to mimic population chronic exposure, rats were contaminated during 9 months through drinking water (40 mg/L). In vivo results show that U exposure does not induce neither nephrotoxicity nor sensitivity to increase a renal toxicity induced by gentamicin. In the liver, U provokes impairments on the XME gene expression. Nevertheless, paracetamol metabolism is modified only if it is administrated at a hepatotoxic dose. The in vitro results suggest an indirect effect of uranium on the XME, probably dependant of body adaptation mechanisms. Besides, in vitro studies underlined cytotoxic properties of U as well as the localisation of its soluble and/or precipited forms in cytoplasmic and nuclear compartments
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Aslangul, Élisabeth. "Résistance de niveau intermédiaire à la gentamicine chez Enterococcus faecalis : sélection, étude du mécanisme et impact thérapeutique." Paris 7, 2005. http://www.theses.fr/2005PA077194.
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Le traitement des infections graves à entérocoque nécessite l'association synergique d'un antibiotique actif sur la paroi bactérienne (amoxicilline ou glycopeptide) à la gentamicine. Les résistances acquises aux antibiotiques touchent ces trois classes chez Enterococcus. L'impact de ces résistances ainsi que les facteurs prédictifs de l'activité des antibiotiques in vivo déterminent l'attitude thérapeutique probabiliste. Les entérocoques VanB sont résistants à la vancomycine, mais sensibles à la teicoplanine. Les monothérapies de chaque glycopeptide et de gentamicine sont inefficaces et elles sélectionnent des mutants résistants. Seule l'association de la teicoplanine et de la gentamicine prévient l'émergence de la résistance. La résistance à la gentamicine de haut niveau (CMI ≥ 500 μg/ml) conférée par des enzymes, empêche les synergies. Nous décrivons un nouveau mécanisme de résistance à la gentamicine chez Enterococcus, par défaut de transport actif. La synergie avec Pamoxicille est perdue si la résistance est de haut niveau<br>The association of a cell-wall active antibiotic (amoxicillin or glycopeptid) with gentamicin is required to treat severe enterococcal infections. Aquired antibiotic resistance in enterococci affects glycopeptides, especially vancomycin, and gentamicin. VanB enterococci are resistant to vancomycin, susceptible to teicoplanin. Both glycopeptides and gentamicin alone selected resistant mutants in E. Faecalis. The association of teicoplanin and gentamicin was efficient and prevented the emergence of resistance. High level gentamicin resistance (MIC ≥ 500 μg/ml) is confered by modifying enzymes in enterococci and prevents synegism. We described a new gentamicin mechanism of resistance in E. Faecalis, by uptake impairement wich prevent Amo synergism when the MIC is greater than 500 μg/ml. Time-kill curves are not predictive of the efficacy in vivo. We developped a new non isotopic method of intracellular gentamicin concentration determination
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Plante, Isabelle. "Étude de la néphrotoxicité induite par l'association médicamenteuse gentamicine-amphotéricine B, effet de l'heure d'administration." Thesis, National Library of Canada = Bibliothèque nationale du Canada, 2001. http://www.collectionscanada.ca/obj/s4/f2/dsk3/ftp04/MQ60648.pdf.
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Rafael, Leandro Américo [UNESP]. "Avaliação do efeito trombogênico da perfusão regional intravenosa com gentamicina em equinos." Universidade Estadual Paulista (UNESP), 2012. http://hdl.handle.net/11449/88977.
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rafael_la_me_botfmvz.pdf: 598677 bytes, checksum: 9244a6bf719ef84e48cb12aef3188a32 (MD5)<br>Coordenação de Aperfeiçoamento de Pessoal de Nível Superior (CAPES)<br>Os processos sépticos são complicações frequentes nas estruturas sinoviais e demais tecidos da porção distal dos membros de equinos. A perfusão regional intravenosa é uma opção terapêutica, que objetiva aumentar significativamente a concentração de antimicrobiano na porção distal ao posicionamento do torniquete. No entanto, alguns pontos ainda não estão totalmente esclarecidos e algumas complicações, como trombose venosa, podem ocorrer. Objetivou-se com este estudo avaliar o potencial trombogênico da perfusão regional de gentamicina, na dose de 2,2 mg/kg na veia cefálica de equinos. Utilizou-se 15 equinos hígidos, divididos em três grupos de cinco animais. Grupo 1, somente torniquete (GT), grupo 2, torniquete e 40 ml de solução fisiológica (GSF), grupo 3, torniquete e gentamicina na dose de 2,2 mg/kg e solução fisiológica até completar um volume de 40 ml (GSG). Um membro torácico de cada animal foi escolhido aleatoriamente para o tratamento e torniquete aplicado no terço médio proximal do rádio. Ultrassonografia Doppler foi realizada no membro testado imediatamente antes, 30 minutos, 2, 3, 4, 6, 12, 24, 48, 72 e 96 horas após o tratamento na veia cefálica e artéria mediana. A artéria mediana também foi avaliada aproximadamente 15 minutos após posicionamento do torniquete. A termografia foi realizada em ambos os membros em todos os momentos. Os dados foram avaliados por análise de variância com medidas repetidas, teste de Tukey de comparações múltiplas de médias para comparar os grupos e ajustado para Dunnett para comparar os momentos em relação ao momento M0. Significância foi aceito p <0,05. Todos os grupos apresentaram escore trombótico zero, não houve diferença significativa entre os grupos quanto à temperatura do membro e diâmetro médio da veia. A perfusão regional intravenosa com...<br>Septic processes are common in synovial structures and tissues of the distal limbs in horses. Regional intravenous perfusion is a therapeutic option that aims to significantly increase the antibiotic concentration in the limb, distal to the tourniquet. Nevertheless, some critical points remains unclear, and complication such as thrombosis may occur along this procedure. The purpose of this work was to assess the thrombogenic potential of regional intravenous perfusion after administration of gentamicin in the cephalic vein. Fifteen healthy horses were assigned to three groups of 5 animals. Group 1, tourniquet group (TG), group 2, tourniquet and 40 mL of physiologic saline solution (SPG) and group 3, tourniquet and 2.2 mg/kg gentamicin completed to 40 mL by addition of physiologic saline solution (ASG). One forelimb of each animal was randomly chosen for treatment and tourniquet applied at the proximal end of the radius. Doppler ultrasonography was performed in the treated limb immediately before and 30 minutes, 2, 3, 4, 6, 12, 24, 48, 72 and 96 hours after treatment in the cephalic vein and artery median. The median artery was also evaluated approximately 15 minutes after placement of the tourniquet. Thermography was performed in both limbs at all the moments. Data were assessed by analysis of variance with repeated measures, Tukey's multiple mean comparison test to compare the groups and Dunnett's multiple mean comparison test to compare the moments regarding M0. Significance was accepted at p <0.05. Thrombotic score was zero for the three groups; no difference was found between groups regarding temperature and mean vein diameter of the treated limb. Regional intravenous perfusion using a single dose... (Complete abstract click electronic access below)
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Rafael, Leandro Américo. "Avaliação do efeito trombogênico da perfusão regional intravenosa com gentamicina em equinos /." Botucatu : [s.n.], 2012. http://hdl.handle.net/11449/88977.
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Orientador: Celso Antônio Rodrigues<br>Banca: Carlos Alberto Hussni<br>Banca: Luis Cláudio Lopes Correia da Silva<br>Resumo: Os processos sépticos são complicações frequentes nas estruturas sinoviais e demais tecidos da porção distal dos membros de equinos. A perfusão regional intravenosa é uma opção terapêutica, que objetiva aumentar significativamente a concentração de antimicrobiano na porção distal ao posicionamento do torniquete. No entanto, alguns pontos ainda não estão totalmente esclarecidos e algumas complicações, como trombose venosa, podem ocorrer. Objetivou-se com este estudo avaliar o potencial trombogênico da perfusão regional de gentamicina, na dose de 2,2 mg/kg na veia cefálica de equinos. Utilizou-se 15 equinos hígidos, divididos em três grupos de cinco animais. Grupo 1, somente torniquete (GT), grupo 2, torniquete e 40 ml de solução fisiológica (GSF), grupo 3, torniquete e gentamicina na dose de 2,2 mg/kg e solução fisiológica até completar um volume de 40 ml (GSG). Um membro torácico de cada animal foi escolhido aleatoriamente para o tratamento e torniquete aplicado no terço médio proximal do rádio. Ultrassonografia Doppler foi realizada no membro testado imediatamente antes, 30 minutos, 2, 3, 4, 6, 12, 24, 48, 72 e 96 horas após o tratamento na veia cefálica e artéria mediana. A artéria mediana também foi avaliada aproximadamente 15 minutos após posicionamento do torniquete. A termografia foi realizada em ambos os membros em todos os momentos. Os dados foram avaliados por análise de variância com medidas repetidas, teste de Tukey de comparações múltiplas de médias para comparar os grupos e ajustado para Dunnett para comparar os momentos em relação ao momento M0. Significância foi aceito p <0,05. Todos os grupos apresentaram escore trombótico zero, não houve diferença significativa entre os grupos quanto à temperatura do membro e diâmetro médio da veia. A perfusão regional intravenosa com... (Resumo completo, clicar acesso eletrônico abaixo)<br>Abstract: Septic processes are common in synovial structures and tissues of the distal limbs in horses. Regional intravenous perfusion is a therapeutic option that aims to significantly increase the antibiotic concentration in the limb, distal to the tourniquet. Nevertheless, some critical points remains unclear, and complication such as thrombosis may occur along this procedure. The purpose of this work was to assess the thrombogenic potential of regional intravenous perfusion after administration of gentamicin in the cephalic vein. Fifteen healthy horses were assigned to three groups of 5 animals. Group 1, tourniquet group (TG), group 2, tourniquet and 40 mL of physiologic saline solution (SPG) and group 3, tourniquet and 2.2 mg/kg gentamicin completed to 40 mL by addition of physiologic saline solution (ASG). One forelimb of each animal was randomly chosen for treatment and tourniquet applied at the proximal end of the radius. Doppler ultrasonography was performed in the treated limb immediately before and 30 minutes, 2, 3, 4, 6, 12, 24, 48, 72 and 96 hours after treatment in the cephalic vein and artery median. The median artery was also evaluated approximately 15 minutes after placement of the tourniquet. Thermography was performed in both limbs at all the moments. Data were assessed by analysis of variance with repeated measures, Tukey's multiple mean comparison test to compare the groups and Dunnett's multiple mean comparison test to compare the moments regarding M0. Significance was accepted at p <0.05. Thrombotic score was zero for the three groups; no difference was found between groups regarding temperature and mean vein diameter of the treated limb. Regional intravenous perfusion using a single dose... (Complete abstract click electronic access below)<br>Mestre
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Hiel, Hakim. "Distributions cellulaire et subcellulaire de la gentamicine dans l'oreille interne et développement de l'ototoxicité chez le cobaye." Bordeaux 2, 1991. http://www.theses.fr/1991BOR28149.
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Les travaux presentes sur le developpement de l'ototoxicite de l'antibiotique aminoglycosidique, la gentamicine, et sa localisation cellulaire et subcellulaire dans les tissus de l'oreille interne nous ont permis de tirer les conclusions suivantes: 1) la gentamicine est specifiquement distribuee dans les cellules ciliees sensorielles cochleaires et vestibulaires apres un traitement chronique ou aigu. 2) la localisation de la gentamicine suit un gradient baso-apical et radial dans la cochlee et est en bonne correlation avec les alterations morpho-fonctionnelles. 3) au niveau subcellulaire, ce sont les lysosomes sous la plaque cuticulaire qui apparaissent comme les sites essentiels d'accumulation de la gentamicine. 4) de facon surprenante on detecte la gentamicine dans les cellules cibles bien avant les modifications electrophysiologiques lors d'un traitement chronique. 5) l'activation des cellules sensorielles semble etre un processus essentiel au developpement de l'ototoxicite puisqu'une stimulation sonore non traumatisante (60 a 70 db spl) favorise la penetration de la molecule toxique et l'apparition des alterations fonctionnelles. 6) l'elimination de la gentamicine des cellules ciliees apparait comme un phenomene extremement lent et doit certainement etre un facteur important dans le developpement des mecanismes de cytotoxicite conduisant a la mort cellulaire
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Zamarreño, Beas Jordi. "Study of molecular mechanisms allowing E. coli to resist against antibiotics." Thesis, Aix-Marseille, 2018. http://www.theses.fr/2018AIXM0581/document.
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La résistance aux antibiotiques est devenue un problème de santé publique majeur. Comprendre les mécanismes moléculaires menant à la résistance aux antibiotiques et ceux qui permettent la sensibilisation est capital pour trouver des nouvelles manières de combattre les bactéries multirésistantes. La concentration intracellulaire en antibiotiques est un paramètre clé qui influe sur la sensibilité bactérienne aux antibiotiques. Au cours de ma thèse, j'ai étudié trois mécanismes différents modulant la concentration intracellulaire d'antibiotiques chez E. coli.Tout d'abord, j'ai montré que RavA, une ATPase AAA+, et son partenaire ViaA, sensibilisent E. coli aux aminoglycosides en augmentant la concentration intracellulaire d'antibiotiques. Contrairement au modèle actuellement en vigueur dans la littérature, j'ai montré que RavA et ViaA ne requièrent ni les machineries de biogénèse des centres Fe-S, ni les complexes respiratoires contenant des centres Fe-S pour sensibiliser E. coli aux aminoglycosides. Un nouveau modèle sera discuté.Enfin, dans une étude en collaboration avec l'équipe de Nassos Typas qui a analysé à très large échelle l'effet des antibiotiques en combinaison avec différentes molécules, j'ai étudié les combinaisons ayant un effet antagoniste avec les aminoglycosides. En réalisant des tests d'import de gentamicine avec 8 combinaisons différentes, j'ai montré que l'effet antagoniste était dû à une diminution de la concentration intracellulaire de gentamicine dans 7 des 8 combinaisons antagonistes testées<br>Antimicrobial resistance is becoming an issue of major public health concern. Understanding the molecular mechanisms leading to antibiotic resistance or sensitization is of major interest to find out new manners to fight superbugs. Modulation of intracellular concentration of antibiotics is one of the most frequent processes leading to antibiotics resistance. My thesis focused on studying three different mechanisms that modulate intracellular antibiotic concentration in E. coli.First, I showed that RavA, an AAA+ ATPase, and its VWA-containing partner, ViaA, sensitize Escherichia coli to aminoglycosides by increasing the intracellular concentrations of the drug. In physiological conditions, the RavA-ViaA aminoglycosides sensitization occurred in anaerobic conditions. To understand the molecular mechanism of such effect I developed genetic approach. I showed that in contrast to what was previously thought, RavA and ViaA acted neither with Fe-S cluster biogenesis machineries (ISC and SUF) nor with Fe-S cluster-containing respiratory complexes. Alternative model will be discussed.Last, in a collaborative work that analysed the effect of almost 3,000 dose- resolved combinations of antibiotics, I focused on drugs antagonizing aminoglycosides. The antagonistic drug combinations identified were highly conserved in six strains from three Gram-negative pathogens, E. coli, Salmonella enterica serovar Typhimurium and Pseudomonas aeruginosa. By performing aminoglycosides uptake assays with 8 different drug-gentamicin combinations, I showed that for 7 out of the 8 antagonistic combinations tested, a decreased in the intracellular concentration of aminoglycosides occurred
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Boyce, Marilynn Audrey. "Effects of body weight and composition on gentamicin volume of distribution." Thesis, University of British Columbia, 1988. http://hdl.handle.net/2429/27801.
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Gentamicin is an aminoglycoside antibiotic that possesses bactericidal activity against many gram-positive and gram-negative organisms. Clinically, it is used most often to treat life-threatening infections due to Pseudomonas, Proteus, and the Klebsiella-Enterobacter group.
A relationship between gentamicin serum concentrations and clinical response has been demonstrated. Toxicities, notably ototoxicity and nephrotoxicity, are also associated with serum concentrations. Gentamicin is given intermittently either intramuscularly or intravenously resulting in peak and trough concentrations. The therapeutic range is defined as peak concentrations between 4-15mg/L (depending in part on the site of infection and the susceptibility of the infecting organism), and trough concentrations less than 2mg/L (to minimize toxicity).
Gentamicin distributes into a space similar to the extracellular fluid volume (ECFV). Pathophysiologic changes which alter the extracellular fluid compartment also alter gentamicin volume of distribution (Vd). One intrinsic factor known to alter gentamicin Vd is obesity. Leanness is also thought to alter gentamicin Vd but its effect has not been quantitated.
The objectives of this study were to: 1) accurately describe a Vd in "normal" patients, that is, those with no factors known to alter gentamicin volume of distribution; 2) determine if there is a continuous linear relationship between gentamicin volume of distribution (L/kg) and percent body fat; 3) determine if that relationship is associated with changes in ECFV; and 4) develop a formula for predicting Vd in a similar patient population.
Twenty patients with no extrinsic factors known to alter gentamicin Vd participated in the study. Five blood samples were drawn around one steady state dose of gentamicin. A one-compartment model was used to calculate Vd. Tritiated water and anthropometric measurements were conducted simultaneously to provide estimates of body composition. Together these values were used to examine the relationship between gentamicin Vd and body composition.
We have described a Vd for gentamicin that is larger but no less variable than is currently used to determine initial dosage regimens. This volume may be larger either due to the selection of patients or method of serum gentamicin analysis. This larger volume should be used to calculate empiric dosage regimens for similarly selected patients to decrease the risk of treatment failure.
We were not able to describe a linear relationship between percent body fat and gentamicin volume of distribution. We have postulated several reasons as to why this relationship could not be detected; 1) the sample size may not have been large enough, 2) the relationship is not important in patients who are not at extremes of weight, or 3) the variations caused by changes in body composition were not as significant as other factors that may cause fluid alterations in hospitalized patients. There was a strong correlation between gentamicin Vd and total body water noted. Having eliminated all patients in whom the relationship between total body water and ECFV could not be assumed to be normal and constant, we have indirectly demonstrated a strong relationship between ECFV and gentamicin Vd. This relationship still leaves variability in gentamicin's distribution characteristics to be explained.
The predictive formula is based on measurements of height, weight, and a larger Vd [L/kg(ideal body weight)] than has previously been used. The predictive formula recommended for clinical use in adults is Vd=0.30L/kg (Dosing Weight). Dosing weight equals ideal body weight (IBW) when actual body weight (ABW) is ≤ IBW, or 0.4(ABW-IBW)+IBW, when ABW is > IBW. The consequences of estimating a larger Vd are that patients empirically would receive larger doses than are currently being administered, thus more patients should obtain therapeutic serum concentrations within the first 24 hours of therapy. This information will be useful in our attempts to optimize gentamicin therapy.<br>Pharmaceutical Sciences, Faculty of<br>Graduate
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Ninauve, Aude. "Etude de la stabilité de mélanges pour nutrition parentérale totale pendant la perfusion." Paris 5, 1995. http://www.theses.fr/1995PA05P083.
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He, Jing. "Des (bio)nano-composites utilisés dans le traitement d'eaux contaminées par de l'arsenic/gentamicine ou pour des applications médicales." Phd thesis, Université de Grenoble, 2013. http://tel.archives-ouvertes.fr/tel-00988092.
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Les composés dits 'bionano' (bionanocomposites) apparaissent comme un nouveau groupe de matériaux hybrides nano-structurés. Ils sont issus de la combinaison de polymères naturels et de solides inorganiques et sont de l'ordre du nanomètre dans au moins une direction. Ces matériaux hybrides conservent les structures et les propriétés fonctionnelles des polymères et matériaux inorganiques dont ils sont composés. Parallèlement, la présence de biopolymères permet de diminuer les risques environnementaux et de santés publiques liés aux nano-matériaux. Les propriétés inhérentes aux biopolymères (biocompatibles' et biodégradables) ouvrent des perspectives intéressantes pour ces matériaux hybrides en particulier dans les domaines de la médecine regénérative et en génie de l'environnement. La production de bionanocomposites de taille plus importante, que les nanoparticules qu'ils renferment, permet d'éviter les effets nocifs potentiels des nanoparticules (NPs) pour les organismes vivants et plus particulièrement pour l'homme. L'association de biopolymères et de nano-solides inorganiques permet la conception de bionanocomposites multifonctionnels qui peuvent être synthétisés et utilisés pour des applications dans des domaines variés. Cette thèse se propose d'étudier principalement (i) ma présence d'arsenic et d'antibiotiques dans les sources d'eau potable en Chine; (ii) l'évaluation d'un nouveau bionanocomposites, à savoir le CGB (chitosan goethite bionanocomposite), dans la décontamination des eaux contenant des espèces inorganiques d'arsenic; (iii) l'évaluation d'argiles comme adsorbants de décontamination de la gentamicine (un antibiotique aminoglycoside ) présent dans l'eau de même que celle de bionanocomposés fait d'argiles riches en gentamicine de polymères de methycelluloses hydroxypropyles Gt-Mt-HPMC (gentamicin-montmorillonite- hydroxypropyl methycellulose) utilisés comme pansement contre les infections qui ont lieu suite à des brûlures.
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Giraudet, Fabrice. "La sensibilité cochléaire aux traumatismes acoustiques chez le cobaye tricolore : implication du système nerveux sympathique issu du ganglion cervical supérieur." Aix-Marseille 3, 2003. http://www.theses.fr/2003AIX30029.
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L'innervation sympathique cochléaire issue du ganglion cervical supérieur (GCS) est unilatérale et son rôle est encore obscur. Nous avons montré, chez le cobaye éveillé implanté de façon bilatérale et chronique au niveau de la fenêtre ronde, que suite à l'ablation unilatérale du GCS les pertes auditives temporaires (PAT) induites par une surstimulation acoustique étaient significativement réduites du côté opéré mais également du côté controlatéral. Le profil et la cinétique de récupération des PAT, chez l'animal sédaté (xylazine, agoniste 2 adrénergique) et anesthésié (kétamine, antagoniste glutamatergique), sont similaires à ceux observés chez l'animal éveillé après GCSx. Ces données nous ont conduit à avancer l'hypothèse d'une interaction fonctionnelle entre le système nerveux sympathique et le système efférent olivocochléaire, ce dernier étant connu pour jouer un rôle dans les mécanismes de protection cochléaire contre les traumatismes sonores<br>The ipsilateral projection from the superior cervical ganglion (SCG) to the cochlea has been morphologically described but its functional role has not been clearly defined. We have shown in the awake pigmented guinea pigs with bilateral and chronic round-window electrodes, that following the unilateral ablation of the SCG (SCGx) the temporary threshold shift (TTS), induced by an acoustic overstimulation, was significantly reduced not only in the ear ipsilateral to the SCGx, but also in the contralateral ear. In sedated (xylazine: an 2 agonist) or anaesthetised (ketalar: a glutamate antagonist) animals, TTS was observed to be reduced and the kinetics of recovery were similar to those observed in the animal awake after SCGx. These data led us to hypothesise a functional interaction between the sympathetic nervous system and the olivocochlear efferent system whose projection is bilateral and is known to play a role cochlear protection against the acoustic trauma
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MOUKADDEM, MARIAM. "Etude du mecanisme d'action d'un antibiotique aminoglycosidique, la gentamicine, sur les ribosomes bacteriens issus de souches sensibles et resistantes d'e. Coli." Paris 6, 1987. http://www.theses.fr/1987PA066058.
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SMAOUI, HATEM, and Jean Schaeverbeke. "Nephrotoxicite induite in utero et chez le rat adulte. Etude ultrastructurale et fonctionnelle, approche biochimique de l'effet d'un antibiotique : la gentamicine." Paris 7, 1991. http://www.theses.fr/1991PA077204.
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Le traitement par la gentamicine chez la mere entraine diverses alterations cellulaires des reins de nouveau-nes. Les analyses morphometriques montrent une augmentation significative de l'epaisseur de la lamina densa et de la densite des sites anioniques dans les deux laminae rarae, revelee dans la mbg de animaux traites par des marqueurs cationiques comme le polyethyleneimine et la ferritine cationisee. Les molecules anioniques ont ete identifiees en utilisant l'heparitinase comme etant des heparanes sulfates. Ces degradations sont accompagnees d'une permeabilite accrue de la mbg aux macromolecules. Elles sont egalement observees chez les animaux nouveau-nes, 1 et 6 mois apres la naissance, et chez les animaux adultes. Nous avons note dans les cellules tubulaires proximales des modifications dans la reabsorption des proteines apres un traitement a la gentamicine. Une activite peroxydasique a ete montree dans tous les compartiments d'endocytose a la fois chez les nouveau-nes temoins et chez les meres temoins. Chez les animaux traites, nous avons observe une diminution de la reabsorption de la hrp. Chez le nouveau-ne, la hrp a ete trouvee seulement le long des microvillosites du tubule proximal et n'a pas penetre dans les cellules. Chez la mere, et chez les animaux adultes, l'activite peroxydasique a ete localisee dans les endosomes primaires, alors qu'elle est absente des endosomes tardifs
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Moukaddem, Maryam. "Etude du mécanisme d'action d'un antibiotique animoglycosisique, la gentamicine, sur les ribosomes bactériens issus de souches sensibles et résistants d'E. coli." Grenoble 2 : ANRT, 1987. http://catalogue.bnf.fr/ark:/12148/cb376082674.
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Mauduit, Jacques. "Nouveaux systèmes antibiotiques à libération contrôlée à base de gentamycine et de polymères biorésorbables." Rouen, 1991. http://www.theses.fr/1991ROUES008.
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Cette thèse présente un travail original visant à élaborer des systèmes antibiotiques à libération contrôlée combinant la gentamycine à des polymères biorésorbables et susceptibles de prévenir ou guérir les infections locales parfois observées après une opération chirurgicale. Le mémoire comprend une étude bibliographique faisant le point sur les connaissances actuelles concernant la gentamycine, les poly(acides lactiques) et les systèmes à libération contrôlée. Cette partie est suivie de cinq chapitres dont les quatre premiers traitent des systèmes suivants: 1) combinaisons gentamycine/poly(acide DL-lactique) amorphe de faibles masses moléculaires, pour l'élaboration de formes pâteuses; 2) combinaisons gentamycine/poly(acide L-lactique) semi-cristallins, en fin de compte inadaptées aux objectifs; 3) combinaisons gentamycine/poly(acide DL-lactique) de hautes masses moléculaires, sous forme de particules; 4) combinaisons gentamycine/mélange de poly(acide DL-lactique) de faibles et de hautes masses moléculaires, de compositions variées, sous forme de films résistants plus ou moins rigides. Le dernier chapitre présente les études in vivo des formes particules et films. Les caractéristiques pharmacocinétiques des systèmes testés sont compatibles avec les cahiers des charges correspondants et répondent apparemment aux objectifs initiaux
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Soares, Paolo Neandro Bona. "Avaliação in vitro do polímero de mamona associado ao carbonato de cálcio com gentamicina como dispositivo de liberação de antibióticos." Universidade de São Paulo, 2012. http://www.teses.usp.br/teses/disponiveis/10/10137/tde-11062013-144702/.
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Na medicina equina, procedimentos cirúrgicos ortopédicos, principalmente os que envolvem fixação de fratura, apresentam um grande índice de infecção e mortalidade. Diferentes métodos de liberação local de antibiótico têm sido utilizados com sucesso na profilaxia e tratamento das infecções musculoesqueléticas. O objetivo da presente investigação foi avaliar a capacidade da poliuretana de mamona como dispositivo de liberação local de antibiótico in vitro já que não existem relatos deste polímero para tal finalidade, além de analisar o efeito bactericida da gentamicina liberada pelo polímero. Foram confeccionados 40 corpos de prova de polímero de mamona, divididos igualmente em 4 grupos, sendo um grupo controle, este sem adição de sulfato de gentamicina e três grupos com diferentes concentrações de gentamicina (6, 12 e 24 mg/g de polímero), onde avaliou-se a liberação de gentamicina em solução PBS com pH 7,4 através da espectrofotometria colorimétrica com reação da ninhidrina em diferentes dias (01, 02, 07, 14, 21 e 28). A espectrofotometria colorimétrica com reação da ninhidrina não se mostrou o método de análise adequado para avaliar a liberação a partir deste polímero, porém a poliuretana de mamona mostrou-se efetiva como mecanismo de liberação de gentamicina quando avaliada in vitro em culturas de S. aureus.<br>In equine medicine, orthopedic procedures, especially those involving fracture fixation, presented a high rate of infection and mortality. Different methods of local release of antibiotics have been used successfully for prophylaxis and treatment of orthopaedic infections. The objective of this research was to evaluate the ability of castor oil polyurethane as a controlled release local antibiotic in vitro since there are no reports of this polymer for this purpose and the bactericidal effect of gentamicin released. Were prepared 40 samples of castor oil polymer, divided equally into four groups, one control group, without this addition of gentamicin sulfate and three groups with different concentrations of gentamicin (6, 12 and 24 mg / g of polymer) that was evaluated the release of gentamycin in PBS at pH 7.4 by spectrophotometry colorimetric reaction with ninhydrin in different days (01, 02, 07, 14, 21 and 28). The spectrophotometry colorimetric reaction with ninhydrin did not prove to be an appropriate method of analysis for assessing the release from this polymer, but the castor oil polyurethane proved to be an effective as a mechanism for release of gentamicin when evaluated in vitro in cultures of S. aureus
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Zayane, Saïd. "Evaluation des granules de phosphate dicalcique di-hydraté-phosphate tricalcique B-gentamicine dans le traitement local de l'ostéite expérimentale à Staphylococcus aureus." Thesis, Tours, 2010. http://www.theses.fr/2010TOUR3302/document.
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Le traitement antibiotique local de l'infection osseuse par le polyméthacrylate de méthyle (PMMA), chargé de gentamicine ou de tobramycine, montre actuellement des limites. Ses inconvénients sont liés à la non résorbabilité du PMMA et à la rétention d'une grande partie de l'antibiotique intégré au PMMA. L’association fréquente à l’infection de pertes de substance osseuse a favorisé la recherche de vecteurs d’antibiothérapie locale, alternative au PMMA, parmi les substituts de comblement osseux résorbables et ostéoconducteurs. Les ciments phosphocalciques (CPC) pourraient devenir parmi les plus performants dans cette utilisation. Ils sont biocompatibles et offrent avec le Dicalcium Phosphate-ß-Tricalcium Phosphate (DCPD-ß-TCP), un CPC, la possibilité d'obtention d'un mélange DCPD-ß-TCP-gentamicine à une température de 43°C n'altérant pas l'antibiotique, contrairement aux céramiques phosphocalciques qui sont fabriquées par frittage à très haute température. Le but de notre travail était de tester in vitro (élution d’antibiotique) et in vivo (essai de traitement d'ostéite expérimentale) le DCPD-ß-TCP-gentamicine comme alternative possible au PMMA-gentamicine. [...]<br>Local antibiotic treatment of osteomyelitis is based on the use of gentamicin- (or tobramycin-) loaded polymethylmethacrylate (PMMA). These two aminoglycosides are effective against most cultured orthopedic microorganisms, including Staphylococcus aureus, the most frequent cause of infection. The extensive use of PMMA as a Local Antibiotic Delivery System (LADS) has various disadvantages. Firstly, only a small proportion (about 5 to 17%) of the antibiotic is released by the cement (trapping effect). Secondly, the most significant problem is that PMMA is not resorbable and presents a physical obstacle to osteogenesis. A second surgical operation is therefore always required to remove the PMMA and to fill the cavity caused by bone loss with a bone graft or a synthetic substitute. Several absorbable synthetic substitutes, such as calcium phosphate ceramics, calcium sulfate, and polymers of polylactic-polyglycolic acids, have been investigated as antibiotic carriers. These synthetic substitutes are largely underused as LADS in clinical practice. Polymers are not perfectly biocompatible, and ceramics provide a burst release of antibiotics as a consequence of their manufacturing techniques (Antibiotic adsorption onto the carrier, after sintering of the carrier at high temperature, 1000-1200°C). We have developed a possible alternative to gentamicin loaded-PMMA for local treatment of osteomyelitis in the form of novel calcium phosphate cement (CPC): dicalcium phosphate dihydrate-β-tricalcium phosphate (DCPD-β-TCP). The biocompatibility of such a cement has been demonstrated experimentally and has been clinically confirmed for the treatment of burst fractures and for filling bone cavities in osteoporotic fractures. DCPD-ß-TCP is made in granules from 2 to 3 mm in diameter to avoid the superficial ―creeping substitution‖ observed when DCPD-β-TCP is used as a cement block. [...]
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Pernet, Virginie. "Typage par macrorestriction d'ADN des souches de Staphylococcus aureus résistants à la méticilline et sensibles à la gentamicine isolées en milieu hospitalier entre 1991 et 1995." Paris 5, 1998. http://www.theses.fr/1998PA05P127.
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Šiupšinskaitė, Vaida. "Vaistų monitoringo svarba klinikinėje praktikoje - aminoglikozidinių antibiotikų koncentracijų kraujyje įvertinimas." Master's thesis, Lithuanian Academic Libraries Network (LABT), 2008. http://vddb.library.lt/obj/LT-eLABa-0001:E.02~2008~D_20080616_100302-76220.
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Tikslas: Įvertinti aminoglikozidų koncentracijos tyrimo svarbą racionaliai farmakoterapijai. Nustatyti ir įvertinti amikacino ir gentamicino koncentracijų tyrimų tendencijas Limoges universitetinėje ligonineje (CHU) ir Kauno medicinos universiteto klinikose (KMUK).
Metodai: Duomenys buvo gauti iš CHU farmakologijos – toksikologijos ir statistikos skyrių bei KMUK klinikinės chemijos - hematologijos laboratorijos ir statistikos skyriaus. Apskaičiuota kiek koncentracijos tyrimo tenka vienam lovadieniui per 2007 metus, įvertintos gentamicino ir amikacino ištirtų koncentracijų duomenys bei paskirtos dozės. Duomenų statistinė analizė buvo atlikta naudojant MS Office programų paketo MS Excel skaičiuoklės ir duomenų apdorojimo programos.
Rezultatai: Gentamicinui buvo atlikta 400 koncentracijos tyrimų (184 atvejų Cmax koncentracijai tirti, 216 – Cmin koncentracijai tirti) . Tirti 131 ligoniai (46 moterys ir 85 vyrai), kuriems gentamicino dozė individualiai adaptuota 221 kartą. Amikacinui buvo atlikta 169 koncentracijos tyrimai (82 atvejai Cmax koncentracijai tirti , 87 – Cmin koncentracijai tirti). Tirti 62 ligoniai (24 moterys ir 38 vyrai), kuriems amikacino dozė individualiai adaptuota 92 kartus.
CHU tenka 6,85×10-4 (1:1460) gentamicino koncentracijos tyrimo vienam lovadieniui ir 2,89×10-4 (1:3456) amikacino koncentracijos tyrimo vienam lovadieniui.KMUK tenka 2,77×10-5 ( 1:36089) gentamicino koncentracijos tyrimo vienam lovadieniui. Taigi, CHU 24,72 kartais lenkia KMUK gentamicino... [toliau žr. visą tekstą]<br>Objectives: To evaluate the importance of researh on aminoglicozids for rational pharmacotherapy. To determine and evaluate the tendencies of studies of amikacin and gentamicin concentration in Limoges University Hospital (CHU) and Kaunas University of medicine Hospital (KMUM).
Methods: The data has been received from the department of pharmacology and toxicology and the department of statistics of CHU and from the laboratory of chemistry and hematology and the department of statistics of KMUK. It has been calculated how much concentration study belongs to one bed-day in the year 2007, the data of the studied concentrations of gentamicin and amikacin have been evaluated and the doses have been administered. Statistical analysis of the data has been carried out by the use of MS Excel and data processing programs of MS Office.
Results: 400 concentration studies have been carried out for gentamicin (184 cases for the study of Cmax concentration, 216 cases for the study of Cmin concentration). 131 patients (46 women and 85 men), who have been individually adapted the dose of gentamicin for 221 time, have been studied. 169 concentration studies have been carried out for amikacin (82 cases for the study of Cmax concentration, 87 cases for the study of Cmin concentration). 62 patients (24 women and 38 men), who have been individually adapted the dose of amikacin for 92 times.
In CHU, there is 6.85×10-4 (1:1460) of gentamicin concentration study for one bed-day and 2.89×10-4 (1:345... [to full text]
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Scheibel, Jóice Maria. "Curativos biodegradáveis à base de poli (butileno adipato-co-tereftalato) com incorporação de gentamicina." reponame:Biblioteca Digital de Teses e Dissertações da UFRGS, 2017. http://hdl.handle.net/10183/180655.
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Tradicionalmente, no tratamento de feridas graves o antimicrobiano tópico deve ser aplicado uma a duas vezes ao dia na área lesada para reduzir as infecções. No entanto, os pacientes geralmente sofrem desconforto com a aplicação de drogas tópicas e com a troca de curativos. Nesse contexto, o desenvolvimento de sistemas curativos biodegradáveis contendo fármaco antimicrobiano são fundamentais para a promoção de ações terapêuticas, reduzindo as infecções causadas por microrganismos e podendo substituir os curativos convencionas que não possuem polímeros biodegradáveis em sua composição. Para ir de encontro com essa necessidade, filmes de PBAT e PBAT/gentamicina foram preparados por meio de duas abordagens. Na primeira abordagem filmes de PBAT obtidos por casting foram funcionalizados por radiação UV durante 90 minutos na presença de O2 atmosférico para posterior inserção de gentamicina na superfície através de soluções tampões contendo EDC e gentamicina. A superfície das amostras foi analisada pelo WCA, FTIR-ATR e XPS. A análise antimicrobiana dos filmes também foi realizada. Os resultados para os filmes de PBAT por casting mostram que o tempo de irradiação produziu superfícies altamente hidrofílicas com grupos oxigenados enxertados na superfície do polímero (C=O e C-OH). A análise antimicrobiana indicou que a gentamicina não ligou covalentemente com o PBAT, porém observou-se a presença de nitrogênio na superfície das amostras pela análise de XPS Na segunda abordagem foram preparadas fibras de PBAT e PBAT/gentamicina a partir da eletrofiação. As soluções utilizadas no processo de eletrofiação foram preparadas com diferentes concentrações de gentamicina e passaram por análises de condutividade e viscosidade. As fibras de PBAT e PBAT/gentamicina foram caracterizadas quanto a suas propriedades físico-químicas, morfológicas, térmicas, antimicrobianas e biológicas. Nos resultados obtidos para as fibras de PBAT e PBAT/gentamicina observou-se que não houve mudança nos espectros após a mistura dos materiais, uma vez que as bandas de absorção foram preservadas e não houve o aparecimento de novos picos. A presença da gentamicina modificou a morfologia das amostras, diminuindo o diâmetro das fibras. O grau de intumescimento foi alterado com o acréscimo de gentamicina e houve modificação da morfologia das fibras após 48 horas de imersão em PBS, porém as fibras mantiveram-se presentes. A gentamicina aumentou o grau de molhabilidade das fibras PBAT. As fibras de PBAT/gentamicina possuem atividade antimicrobiana frente às cepas de E. coli e não apresentaram citotoxicidadede acordo com o padrão ISO 10993-5. Estes resultados reforçam que o PBAT pode ser usado como um sistema curativo com incorporação de fármaco, mostrando ser uma alternativa interessante de curativo/adesivo para uso tópico.<br>Traditionally in the treatment of serious wounds, topical antimicrobial should be applied 1–2 times daily to the injured area to reduce infections. However, patients often suffer from discomfort with the application of topical drugs and with the exchange of dressings. In this context, the development of biodegradable curative systems containing antimicrobial drug are fundamental for the promotion of therapeutic actions, reducing the infections caused by microorganisms and being able to substitute conventional dressings that there aren’t biodegradable polymers in their composition. To meet this need, PBAT and PBAT/gentamicin films were prepared using two approaches. In the first approach PBAT films obtained by casting were functionalized by UV radiation for 90 minutes in the presence of atmospheric O2 for subsequent insertion of gentamicin on the surface through buffer solutions containing EDC and gentamicin. The surface of the samples was analyzed by the WCA, FTIR-ATR and XPS. Antimicrobial analysis of the films was also performed. The results for the PBAT films by casting show that the irradiation time produced highly hydrophilic surfaces with oxygenated groups grafted onto the polymer surface (C=O and C-OH). Antimicrobial analysis indicated that gentamycin did not bind covalently with PBAT, but nitrogen was observed on the surface of the samples by XPS analysis In the second approach, PBAT and PBAT/gentamicin fibers were prepared from the electrospun. The solutions used in the electrospun process were prepared with different concentrations of gentamicin and underwent conductivity and viscosity analyzes. The PBAT and PBAT/gentamicin fibers were characterized as their physical-chemical, morphological, thermal, antimicrobial and biological properties. In the results obtained for the PBAT and PBAT/gentamicin fibers, it was observed that there was no change in the spectra after the materials were mixed, since the absorption bands were preserved and there were no new peaks. The presence of gentamicin modified the morphology of the samples, reducing the diameter of the fibers. The degree of swelling was altered with the addition of gentamicin and there was a change in the morphology of the fibers after 48 hours of immersion in PBS, but the fibers remained present. Gentamicin increased the degree of wettability of PBAT fibers. PBAT/gentamicin fibers have antimicrobial activity against E. coli strains and did not present cytotoxicity according to ISO 10993-5 standard. These results reinforce that PBAT can be used as a curative system with drug incorporation, proving to be an interesting dressing/adhesive alternative for topical use.
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Gilbert, Thierry. "Exposition a la gentamicine au cours de la vie foetale : etude du mecanisme et des consequences d'une reduction nephronique acquise in utero chez le rat." Paris 6, 1988. http://www.theses.fr/1988PA066255.
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Simon-Cornu, Marie. "Dynamique des populations bactériennes en cultures mixtes." Lyon 1, 2000. http://www.theses.fr/2000LYO10213.
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Santos, Carla Danielle Silva. "Mineralização biomimética de hidrogéis quitosana/gelatina." Universidade de São Paulo, 2014. http://www.teses.usp.br/teses/disponiveis/75/75135/tde-30012015-102330/.
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Um dos maiores desafios da ortopedia é recuperar o tecido ósseo que tenha sido perdido por motivo de doença ou acidente. Na busca de substitutos para os enxertos, tem-se utilizado comumente biomateriais, para recuperação desse tecido. A quitosana é um polímero biocompatível, biodegradável e juntamente com a gelatina, que é produto da desnaturação do colágeno, possuem uso potencial no área de regeneração de tecidos ósseos. O objetivo deste trabalho é a preparação, caracterização de hidrogéis de quitosana:gelatina mineralizados, em diferentes proporções (1:0,5; 1:1 e 1:2) e estudar a liberação controlada de gentamicina utilizando como suporte o hidrogel mineralizado. A quitosana foi obtida a partir da desacetilação parcial da quitina oriunda de gládios de lula e a gelatina utilizada é a comercial Sigma®. Os hidrogéis foram mineralizados pelo método de imersão alternada em soluções de CaCl2 0,2 mol L-1 pH=7,4 e de Na2HPO4 0,12 mol L-1 pH=9,0. A mineralização foi caracterizada por espectroscopia na região do infravermelho (FTIR), análise termogravimétrica (TG), microscopia eletrônica de varredura (MEV), dispersão de raios-X (EDS), difração de raios-X (DRX) e cinética de absorção em PBS. Nas análises de TG e MEV pode-se observar a ocorrência de mineralização homogênea no hidrogel, aproximadamente 60% (m/m) em todas as proporções. Nos espectros de FTIR, EDS e DRX, observou-se que o sal de fosfato de cálcio formado durante o processo de mineralização alternada corresponde à hidroxiapatita. Quanto ao estudo de absorção em PBS, os hidrogéis mineralizados apresentam menor intumescimento que os não-mineralizados. Estudou-se o comportamento da liberação in vitro (em PBS, pH 7,4) de gentamicina no hidrogel mineralizado de quitosana/gelatina (1:1) quando se altera a temperatura da liberação (25°C e 37°C). A gentamicina foi incorporada ao hidrogel mineralizado através da imersão em uma solução com concentração de 30 mg ml-1 de gentamicina. O estudo de liberação foi realizado em duas temperaturas 25°C e 37°C. A quantidade de fármaco liberado após 24 horas não é afetada pela alteração na temperatura, mas a velocidade da liberação nas duas primeiras horas é maior a 37°C do que a 25°C. O mecanismo de liberação da gentamicina foi ajustado para o modelo Korsmeyer-Peppas sugerindo que segue a difusão Fickiana.<br>The replacement of bone tissue lost due to illness or accident is a great challenge in orthopedic area. Biomaterials have been commonly used to prepare new materials for substitution of lost tissue. Chitosan is a biocompatible and biodegradable polymer and its association with gelatin has potential application in bone tissue regeneration. The objective of this study is to describe the preparation and characterization of mineralized hydrogels of chitosan/gelatin prepared with different ratios (1:0.5, 1:1 and 1:2) and the controlled release of gentamicin using the mineralized hydrogel as a support. Chitosan was obtained from the partial deacetylation of squid pens and gelatin was commercial (Sigma ®). The mineralization process was carried out by the alternate soaking method. Hydrogels were soaked in 0.2 mol L-1 CaCl2 buffered with 0.05 mol L-1 Tris buffer (pH 7.4) at 25°C for 30 min, taken out of the Ca2+ solution, rinsed with deionized water and then soaked in 0.12 mol L-1 Na2HPO4 solution buffered with 0.05 mol L-1 Tris buffer (pH 9.0) for 30 min, taken out of the PO43- solution and rinsed with deionized water. The alternate soaking cycle was repeated 6 times to obtain the mineralized matrices which were then rinsed with water, frozen and lyophilized. Mineralized hydrogels were characterized by infrared spectroscopy (FTIR), thermogravimetric analysis (TG), scanning electron microscopy (SEM), Energy Dispersive Spectroscopy (EDS), X-ray diffraction (XRD) and kinetic absorption in PBS. SEM results showed an homogeneous mineralization, and for all hydrogels a quantity of approximately 60% (w/w) of mineralization was determined by TG. FTIR, EDS and XRD indicated that phosphate calcium deposited during mineralization process was hydroxyapatite. Mineralized hydrogels had lower swelling values in comparison with non-mineralized, as observed by absorption in PBS. Release of gentamicin in mineralized hydrogel was performed at 25°C and 37°C. Gentamicin was incorporated in the mineralized hydrogel by immersion in a gentamicin solution with a concentration of 30 mg ml-1. The change in release temperature showed that the quantity of drug delivery was not affected after 24 hours. However, the release rate in the first hour is higher at 37°C. The release mechanism of gentamicin was adjusted to the Korsmeyer-Peppas model suggesting that drug release is mostly controlled by a diffusion process.
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Magenis, Giovana Bongiolo [UNESP]. "Avaliação da gentamicina aplicada em ovos de aves reprodutoras pesadas e seu efeito residual nos tecidos." Universidade Estadual Paulista (UNESP), 2015. http://hdl.handle.net/11449/127857.
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000845404_20200101.pdf: 177356 bytes, checksum: 9ad739f545c33b71a2af66d49b9e0377 (MD5)<br>A preocupação da indústria avícola em manter altos índices de produtividade e de segurança dos alimentos fez com que surgissem ações preventivas a fim de evitar a introdução de patógenos no sistema avícola. O uso de gentamicina associada à vacinação in ovo tem sido amplamente utilizada com essa finalidade. Neste particular, são escassas as informações disponíveis na literatura acerca da segurança clínica e alimentar da gentamicina quando aplicada in ovo. Diante disto, dois experimentos foram conduzidos para avaliar o efeito da administração da gentamicina em ovos de reprodutoras pesadas nos parâmetros físicos, hematológicos e bioquímicos, e também a permanência desse antimicrobiano nos tecidos de frangos de corte. No primeiro estudo, foram utilizados 200 ovos de matrizes da linhagem Cobb e, aos 18 dias de incubação, 100 ovos receberam apenas a vacina contra a doença de Marek (GC) e os outros 100 receberam a vacina juntamente com 0,22mg/ovo de sulfato de gentamicina (GT). Após o nascimento (D0), foram realizados exames físicos nos momentos D+3, D+6, D+10, D+14 e D+21 (3, 6, 10, 14 e 21 dias após o nascimento, respectivamente), assim como exames complementares em D+6, D+10, D+14 e D+21. Os parâmetros físicos compreenderam pesagem, avaliação da condição corpórea, comportamento, postura/marcha, respiração, apetite, excretas, penas e pele, bem como sinais de intoxicação. Quanto aos parâmetros laboratoriais, foram determinados o hemograma completo e as provas bioquímicas séricas [ureia, ácido úrico, aspartato aminotransferase, alanina aminotransferase (ALT), gama glutamiltransferase (GGT), creatina quinase, albumina e proteínas plasmáticas totais]. Os resultados foram submetidos à análise estatística por meio do procedimento general Linear Models (GLM) do SAS com pós-teste de Tukey, considerando o nível de significância de 5%. Em ambos os grupos, todas as aves se apresentaram saudáveis...<br>The concern of the poultry industry to maintain high levels of productivity and food security has spurred preventive actions in order to prevent the introduction of pathogens in the poultry system. The use of gentamicin associated with in ovo vaccination has been widely used for this purpose. In particular, there is little information available in the literature about the clinical and food safety of gentamicin when applied in ovo. Given this, two experiments were conducted to evaluate the effect of the administration of gentamicin in eggs of breeders in physical, hematological and biochemical parameters, as well as the permanence of this antimicrobial in broiler tissues. In the first study, 200 eggs of Cobb arrays were used and, in the 18th day of incubation, 100 eggs received only vaccination against Marek's disease (CG) and the other 100 received the vaccine with 0.22mg/egg of gentamicin sulfate (GT). After the birth (D0), physical examinations were performed at times D+3, D+6, D+10, D+14 and D+21 (3, 6, 10, 14 and 21 days after birth, respectively), as well as additional tests on D+6, D+10, D+14 to D+21. The physical parameters covered weighing, evaluation of body condition, behavior, posture/gait, breathing, appetite, feces, feathers and skin, as well as signs of intoxication. As for the laboratory parameters, the complete blood count and serum biochemical tests [urea, uric acid, aspartate aminotransferase, alanine aminotransferase (ALT), gamma glutamyl transferase (GGT), creatine kinase, albumin and total plasma proteins] were determined. The results were statistically analyzed using the General Linear Models Procedure (GLM) of SAS with Tukey's test, with a significance level of 5%. In both groups, all birds showed healthy throughout the study and the average body weight was not significantly different between GC and GT. In the complete blood count, despite variations within the same treatment, no significant differences between ...
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Magenis, Giovana Bongiolo. "Avaliação da gentamicina aplicada em ovos de aves reprodutoras pesadas e seu efeito residual nos tecidos /." Jaboticabal, 2015. http://hdl.handle.net/11449/127857.
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Orientador: Maria Rita Pacheco<br>Coorientador: Silvana Martinez Baraldi Artoni<br>Banca: Daniela Oliveira<br>Banca: Otto Mack Junqueira<br>Resumo: A preocupação da indústria avícola em manter altos índices de produtividade e de segurança dos alimentos fez com que surgissem ações preventivas a fim de evitar a introdução de patógenos no sistema avícola. O uso de gentamicina associada à vacinação in ovo tem sido amplamente utilizada com essa finalidade. Neste particular, são escassas as informações disponíveis na literatura acerca da segurança clínica e alimentar da gentamicina quando aplicada in ovo. Diante disto, dois experimentos foram conduzidos para avaliar o efeito da administração da gentamicina em ovos de reprodutoras pesadas nos parâmetros físicos, hematológicos e bioquímicos, e também a permanência desse antimicrobiano nos tecidos de frangos de corte. No primeiro estudo, foram utilizados 200 ovos de matrizes da linhagem Cobb e, aos 18 dias de incubação, 100 ovos receberam apenas a vacina contra a doença de Marek (GC) e os outros 100 receberam a vacina juntamente com 0,22mg/ovo de sulfato de gentamicina (GT). Após o nascimento (D0), foram realizados exames físicos nos momentos D+3, D+6, D+10, D+14 e D+21 (3, 6, 10, 14 e 21 dias após o nascimento, respectivamente), assim como exames complementares em D+6, D+10, D+14 e D+21. Os parâmetros físicos compreenderam pesagem, avaliação da condição corpórea, comportamento, postura/marcha, respiração, apetite, excretas, penas e pele, bem como sinais de intoxicação. Quanto aos parâmetros laboratoriais, foram determinados o hemograma completo e as provas bioquímicas séricas [ureia, ácido úrico, aspartato aminotransferase, alanina aminotransferase (ALT), gama glutamiltransferase (GGT), creatina quinase, albumina e proteínas plasmáticas totais]. Os resultados foram submetidos à análise estatística por meio do procedimento general Linear Models (GLM) do SAS com pós-teste de Tukey, considerando o nível de significância de 5%. Em ambos os grupos, todas as aves se apresentaram saudáveis...<br>Abstract: The concern of the poultry industry to maintain high levels of productivity and food security has spurred preventive actions in order to prevent the introduction of pathogens in the poultry system. The use of gentamicin associated with in ovo vaccination has been widely used for this purpose. In particular, there is little information available in the literature about the clinical and food safety of gentamicin when applied in ovo. Given this, two experiments were conducted to evaluate the effect of the administration of gentamicin in eggs of breeders in physical, hematological and biochemical parameters, as well as the permanence of this antimicrobial in broiler tissues. In the first study, 200 eggs of Cobb arrays were used and, in the 18th day of incubation, 100 eggs received only vaccination against Marek's disease (CG) and the other 100 received the vaccine with 0.22mg/egg of gentamicin sulfate (GT). After the birth (D0), physical examinations were performed at times D+3, D+6, D+10, D+14 and D+21 (3, 6, 10, 14 and 21 days after birth, respectively), as well as additional tests on D+6, D+10, D+14 to D+21. The physical parameters covered weighing, evaluation of body condition, behavior, posture/gait, breathing, appetite, feces, feathers and skin, as well as signs of intoxication. As for the laboratory parameters, the complete blood count and serum biochemical tests [urea, uric acid, aspartate aminotransferase, alanine aminotransferase (ALT), gamma glutamyl transferase (GGT), creatine kinase, albumin and total plasma proteins] were determined. The results were statistically analyzed using the General Linear Models Procedure (GLM) of SAS with Tukey's test, with a significance level of 5%. In both groups, all birds showed healthy throughout the study and the average body weight was not significantly different between GC and GT. In the complete blood count, despite variations within the same treatment, no significant differences between ...<br>Mestre
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Wers, Éric. "Élaboration d'un biomatériau poreux à base d'une matrice vitreuse induisant un phénomène d'ostéoconduction." Thesis, Rennes 1, 2014. http://www.theses.fr/2014REN1S168/document.
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Ce travail de thèse concerne les verres bioactifs purs et dopés pour des applications en tant que biomatériaux en site osseux. Ils sont synthétisés par fusion dans le système SiO₂-CaO-Na₂O-P₂O₅. Quatre éléments métalliques (Zn, Ti, Cu et Ag), présentant des caractéristiques chimiques et physiologiques intéressantes, ont été introduits dans la matrice vitreuse. Leur réactivité chimique et leur cytotoxicité ont été évalués lors de tests in vitro. L'introduction de ces éléments métalliques influe sur les caractéristiques thermiques des verres ainsi que sur la dissolution de la matrice vitreuse, la cinétique et la cristallisation de la couche d'hydroxyapatite. Une bonne prolifération cellulaire a été mise en évidence. En parallèle, une méthode de synthèse d'une vitrocéramique, présentant une microporosité, a été développée par réaction entre TiN et ZnO. Des essais in vitro ont montré un caractère bioactif après 60 jours d'immersion et une absence de cytotoxicité. Ce biomatériau a ensuite été implanté au niveau de la diaphyse fémorale de lapins. Différentes études structurales ont montré la résorption progressive du biomatériau jusqu'à 6 mois d'implantation. Des scaffolds chitosan / verre bioactif ont également été synthétisés et obtenus par lyophilisation. Ils ont été étudiés lors d'essais in vitro. Ils ont servi de support pour la vectorisation de gentamicine. Les résultats obtenus montrent que les teneurs en chitosan et en verre bioactif ont une influence sur la cristallisation de l'hydroxyapatite et le relargage du médicament. Les modèles mathématiques établis montrent que le temps de relaxation des scaffolds dépend de la concentration de départ en gentamicine<br>This research work focuses on the pure and doped bioactive glasses for use as bone biomaterial. They are synthesized by the melting method in the system SiO₂-CaO-Na₂O-P₂O₅. Four metallic elements, presenting interesting chemical and physiological properties, have been introduced in the amorphous matrix. Their chemical reactivity and their cytotoxicity have been evaluated during in vitro assays in simulated body fluid and cell culture media. The introduction of these metallic elements influences their thermal characteristics, the glass matrix dissolution, the kinetic and the crystallization of the hydroxyapatite layer. A good cells proliferation have been showed. In parallel, a method of synthesis of a glass-ceramic, having a microporosity, have been developed by reaction between TiN and ZnO. In vitro assays have showed a bioactive character after 60 days of immersion and a non-cytotoxicity. This biomaterial was implanted in the femoral dyaphisis of rabbits. Different structural studies have showed the gradual resorption of the biomaterial up to 6 months of implantation. Finally, scaffolds chitosan/bioactive glass, obtained by freeze-drying, have also been studied during in vitro assays. They were used as support for the vectorization of gentamicin. The obtained results show that the content of chitosan and bioactive glass have an impact on the crystallization of hydroxyapatite et the release of drug. Mathematic models show that the relaxation time depend on the starting concentration of gentamicin
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Perri-Plandé, Joëlle. "Recherche des effets protecteurs des huiles de poisson enrichies en acides gras oméga-3 insaturés vis à vis de la néphrotixicité de trois xénobiotiques in vivo et in vitro." Bordeaux 2, 1998. http://www.theses.fr/1998BOR28627.
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Boudzoumou-Nganga, Pierre. "Médicaments à effet rénal administrés chez la mère pendant la gestation : néphrotoxicité éventuelle chez le nouveau-né : modulations pharmacologiques du développement fonctionnel rénal foetal et néonatal chez le rat après exposition in-utero à la Gentamicine ou au Furosémide." Nancy 1, 1990. http://docnum.univ-lorraine.fr/public/SCD_T_1990_0550_BOUDZOUMOU_NGANGA.pdf.
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Les aminoglycosides (Gentamicine) ont des effets néphrotoxiciques bien connus ; et le Furosémide (un diurétique) a été démontré induire un retard de la différenciation glomérulaire chez le nouveau-né, après administration chez la mère gestante. Nous avons recherché les conséquences fonctionnelles sur le rein en développement chez le nouveau-né ayant reçu de la gentamicine ou du furosémide in-utero ; puis nous avons étudié les possibilités d'une récupération de la fonction rénale à plus ou moins long terme. Des rates gestantes de race WISTAR ont reçu le médicament à la dose de 75mg/Kg/j. L'étude réalisée chez le nouveau-né exposé in-utero à la gentamicine a montré une altération des paramètres fonctionnels : diurèse, clairance et rapport U/P de la créatinine et des fractions d'excrétion de l'eau et des électrolytes. La néphrotoxicité fonctionnelle ainsi induite par la gentamicine est réversible : la fonction de filtration glomérulaire est compensée plus tôt que la déficience tubulaire de concentration urinaire. Les modifications observées après administration in-utero de furosémide paraissent pouvoir être expliquées par un retard dans la maturation de l'anse de Henlé, entrainant une adaptation morphologique et fonctionnelle des autres segments tubulaires déjà développés. Ainsi se serait peut-être constitué un modèle animal très particulier de l'étude du développement rénal. En conclusion, nos résultats apportent l'évidence d'une perturbation fonctionnelle pendant le développement chez le rat ayant reçu in-utero un médicament à effet rénal. Cette perturbation observée encore longtemps après l'exposition prénatale à la gentamicine ou au furosémide a consisté en un retard général de la croissance et un défaut de concentration urinaire<br>Aminoglycosides (gentamicin) antibiotics well-known for their nephrotoxicity; and furosemide, a widely used diuretic, has been reported to induce a delay in the differentiation of renal glomeruli. We were interested to investigate if the developing kidney could be functionally altered in-utero after administration of either these drugs to the pregnant mother. Drugs were given during two keyperiods of pregnancy: days 7-11 (period of organogenesis) and days 14-18 (beginning of glomeruli differentiation) at the dose of 75mg/Kg/day by i. P. Route. The rat strain was WISTAR. Shortly after birth,variations were observed on diuresis, creatinine clearance, U/P creatinine ratio,fractional excretion of water fractional excretion of electrolytes. The gentamicin-induced nephrotoxicity was reversible, the glomerular function being corrected earlier than the tubular urinary concentrating defect. Furosemide seemed to lead to a delay of development of loop of Henle, suggesting a functional adaptation of other segments of tubule, already mature and functionning. Furthermore, our results provide evidences of functional developmental disturbances (altered growth and urinary concentrating defect) in young rats, lately after prenatal exposure to furosemide or gentamicin. In conclusion, drug administration to mother during pregnancy can lead to a detrmental effect upon the kidney of the newborn and of the young animal
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Schlapp, Monika. "Kollagen/PLGA-Mikropartikel Komposite zur gesteuerten Freigabe von Gentamicin /." Aachen : Shaker, 2001. http://www.gbv.de/dms/bs/toc/32406716X.pdf.
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Vigani, Aline Gonzalez. "Epidemiologia clinica e molecular das infecções de corrente sanguine por Enterococcus faecalis no complexo hospitalar da Universidade Estadual de Campinas." [s.n.], 2008. http://repositorio.unicamp.br/jspui/handle/REPOSIP/311064.
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Orientadores: Maria Luiza Moretti, Raquel Silveira Bello Stucchi<br>Tese (doutorado) - Universidade Estadual de Campinas, Faculdade de Ciencias Medicas<br>Made available in DSpace on 2018-08-13T06:04:56Z (GMT). No. of bitstreams: 1
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Previous issue date: 2008<br>Resumo: O enterococo é o terceiro agente mais freqüente em infecção de corrente sangüínea (ICS) hospitalar, responsável por 10% dessas infecções e está associado com alta letalidade. Durante as duas últimas décadas, o surgimento de alto nível de resistência à gentamicina (HLGR) e resistência à vancomicina adicionaram desafios ao tratamento das infecções por Enterococcus faecalis. Avaliamos as ICSs por E. faecalis no Hospital de Clínicas (HC) da Universidade Estadual de Campinas (Unicamp) identificadas de janeiro de 1999 a dezembro de 2003. Nosso objetivo foi determinar as características clínicas, microbiológicas e moleculares das ICSs por E. faecalis com HLGR e sem HLGR em pacientes internados no HC-Unicamp. ICS foi definida como pelo menos uma cultura de sangue positiva para E. faecalis com ou sem sinais e sintomas associados. Em casos de múltiplos episódios de ICS em um mesmo paciente, somente o primeiro episódio foi considerado. Coletamos informações de prontuários médicos utilizando formulários estruturados. A tipagem molecular de isolados de E. faecalis estocados foi realizada através da técnica de eletroforese em gel com campo pulsátil (PFGE). Identificamos 164 pacientes com ICS por E. faecalis, dos quais 145 (88,4%) foram incluídos neste estudo. Nossos achados demonstraram que pacientes com ICS por E. faecalis são graves. Dentre os 145 pacientes, 128 (88,3%) apresentavam pelo menos uma co-morbidade. Além disso, a realização de procedimento invasivo ou presença de dispositivos invasivos foram freqüentes (75,2%), assim como o uso prévio de antimicrobianos (61,4%). Das 145 ICSs, 66 (45,5%) foram por E. faecalis com HLGR e 79 (54,5%) sem HLGR. Na análise univariada, idade avançada, malignidade hematológica, cateterização urinária e uso prévio de cefalosporinas, quinolonas e carbapenêmicos foram mais freqüentes em pacientes com infecção por HLGR quando comparados com pacientes sem HLGR (p <0,05). A análise multivariada mostrou idade avançada, presença de malignidade hematológica e uso prévio de vancomicina como variáveis independentes associadas com infecção por HLGR (p <0,05). A taxa de letalidade foi de 46,2% e não apresentou diferença estatística significativa entre pacientes com infecção por HLGR (50,0%) e sem HLGR (43,0%) (p= 0,40). Ventilação mecânica e gravidade das co-morbidades foram associadas com óbito (p <0,05). Durante o período de estudo, a taxa de resistência à ampicilina foi de 2,0%; ciprofloxacina, 51,7%; penicilina, 35,1%; e estreptomicina, 27,6%. Nenhum isolado resistente à vancomicina foi identificado. A genotipagem dos 44 isolados disponíveis (32 de pacientes incluídos no estudo e 12 controles) revelou 29 isolados distribuídos em 11 perfis genotípicos e 15 isolados apresentaram perfis genotípicos únicos e distintos. Alguns isolados geneticamente relacionados eram suscetíveis à gentamicina e outros possuíam HLGR, o que pode ser resultado da transferência de gene plasmidial de resistência HLGR entre isolados. Nossos resultados permitem concluir que ICSs por E. faecalis estão associadas com alta taxa de letalidade e são freqüentemente causadas por HLGR. Medidas de controle de infecção, incluindo vigilância ativa, respeito às normas de precauções de contato e uso criterioso de antimicrobianos devem ser consideradas para reduzir o risco de transmissão de E. faecalis resistentes em ambiente hospitalar.<br>Abstract: Enterococus is the third most frequent agent in nosocomial blood stream infection (BSI), accounting for 10% of nosocomial BSI, and is associated with high mortality. During the last two decades, the emergence of high-level gentamicin resistance (HLGR) and vancomycin resistance added additional challenges in the treatment of Enterococcus faecalis infections. We evaluated E. faecalis BSI at the Hospital de Clínicas (HC) of the Universidade Estadual de Campinas (Unicamp) in Brazil between January 1999 and December 2003. We sought to determine the clinical, microbiological, and molecular characteristics of BSI caused by HLGR and non-HLGR strains. E. faecalis BSI was defined as at least one positive blood culture for E. faecalis during the study period with or without associated symptoms. In patients with multiple BSI episodes, only the first episode was considered. We collected information from medical charts using standard forms. Banked E. faecalis isolates were typed using pulsed field gel electrophoresis (PFGE). We identified 164 patients with E. faecalis BSI, 145 (88.3%) patients were included in this study. Our data showed that patients with E. faecalis BSI are severely ill. One hundred twenty-eight (88.3%) patients had some underlying chronic disease. Invasive procedure or invasive device (75.2%) and previous use of antimicrobial (61.4%) were also frequent. Of the 145 BSIs, 66 (45.5%) were due to HLGR isolates and 79 (54.5%) were non-HLGR. In the univariate analysis, patients with HLGR infection were older, had hematological malignancy, had higher rates of bladder catheterization, and more often had treatment with cephalosporin, quinolone, and carbapenem when compared with non-HLGR infection patients (p <0.05). Multivariate analysis indicated that older age, hematological malignancy, and previous use of vancomycin were independent risk factors associated with HLGR (p <0.05). Mortality rate was 46.2% and was not statistically significantly different among patients with HLGR (50.0%) and non-HLGR (43.0%) infections (p= 0.40). Multivariate analysis indicated that mechanical ventilation and severity of underlying chronic diseases were associated with death (p <0.05). During the study period, the prevalence of resistance to ampicilin was 2.0%; to ciprofloxacin, 51.7%; to penicillin, 35.1%; and to streptomycin, 27.6%. We did not detect any isolate resistant to vancomycin. We genotyped 44 available isolates, 32 from study patients and 12 controls. Twenty-nine isolates were distributed in 11 PFGE patterns, the remaining 15 isolates had distinct and unique PFGE patterns. Some isolates with related PFGE pattern were HLGR and others non-HLGR, this may have result from transference of HLGR resistance plasmidial between isolates. Our results suggest that E. faecalis BSI are associated with high mortality and are frequently caused by HLGR. Hospital infection control measures, including active surveillance and judicious use of antibiotics, should be considered to reduce the spread of resistant E. faecalis infections in healthcare settings.<br>Doutorado<br>Clinica Medica<br>Doutor em Clínica Médica
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Reva, Anna. "Enzymology of gentamicin biosynthesis." Thesis, University of Cambridge, 2018. https://www.repository.cam.ac.uk/handle/1810/277902.
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Gentamicin C complex is a mixture of five structurally similar aminoglycoside antibiotics, gentamicins C1, C1a, C2, C2a, and C2b, produced by the actinomycete bacterium Micromonospora echinospora. It is established in clinical use and despite significant toxicity remains valuable to treat severe Gram-negative bacterial infections. There is a pressing need to develop novel versions of such antibiotics to combat the rise of resistance among pathogens. Engineering of the pathway requires a detailed knowledge of the genes, enzymes, and intermediates involved. The final steps of gentamicin biosynthesis begin at gentamicin X2, the last common intermediate of the C complex. 6'-C-Methylation generates two branches, with analogous reactions happening in both. Candidate genes and enzymes for the steps from the first 6'-C-methylated intermediate, G418, to an aminated metabolite JI-20B have already been described, but none for the subsequent loss of two hydroxyl groups from Ring II, or the N-methylation that then occurs. A novel separation method using dynamic countercurrent chromatography was successfully applied to the difficult purification of gentamicin metabolites. The results described here allowed a detailed mechanism to be proposed for almost the entire pathway from G418 to the C complex, and by analogy for the unbranched pathway, too. The last step of the pathway is 6'-N-methylation of gentamicins C1a and C2. Genome mining and cell-free assays were used by the group of Professor Yuhui Sun (Wuhan University) to identify genL, a methyltransferase gene encoded elsewhere on the M. echinospora genome and capable of this catalysis. Here, in vitro reactions with recombinant GenL confirmed its function, and its kinetic parameters were measured with its substrates. The full mechanistic pathway for the late stages of gentamicin C complex biosynthesis has therefore now been elucidated.
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Ferreira, Fernando Ribeiro. "Síntese, caracterização e aplicação biológica de hidroxiapatita: em presença de gelatina e associada a sulfato de gentamicina." UNIVERSIDADE ESTADUAL DE PONTA GROSSA, 2009. http://tede2.uepg.br/jspui/handle/prefix/2069.
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Previous issue date: 2009-02-27<br>Coordenação de Aperfeiçoamento de Pessoal de Nível Superior<br>The use of biomaterials comes from old times and recently bioceramics have been deeply investigated as a source of material for bone implant. Amongst the different biomaterials, hydroxyapatite (HA) has great importance for being one of the
compounds which forms the bone mineral phase. Therefore, HA has been largely studied, mainly due to the fact that it is a bioactive compound. Calcium phosphate synthesis via precipitation presents great advantages such as low cost and simplicity, but most procedures described in literature regard the formation of non stoichiometric products and phase mixture. This work studied the HA synthesis by analyzing the
influence of gelatin concentration in the precipitation means on the characteristics of the hydroxyapatite obtained. Gentamicin was also incorporated to the HA samples
and antimicrobial activity was analyzed. The hydroxyapatite was obtained through precipitation in aqueous and gelatin means, being later on dried, sieved and calcined at 700ºC. Gelatin concentrations of 1, 6, 10 and 60 g.L-1 were used. Then, gentamicin sulfate was added, 1% in mass. Samples were characterized through Xray diffraction, specific superficial area through the BET method, thermal analysis,
infrared spectroscopy and transmission and scanning electronic microscopy. The Xray diffraction revealed the presence of HA phase in all samples; and by refining
through the Rietveld method, it could be seen, in the gelatin free sample, the presence of calcium carbonate and pure HA, for the sample prepared in gelatin, indicating that the presence of gelatin made the hydroxyapatite phase stable. XRF and EDS indicated that Ca/P ratio was slightly above what had been expected to obtain stoichiometric hydroxyapatite. The granulometric distribution analysis and
superficial area through the BET method indicated differences in the average size of agglomerates and the superficial area of the material in relation to the synthesis and samples preparation process to receive the antibiotic, which was processed through milling in a ball mill. SEM and TEM revealed morphological and structural aspects characteristic of the hydroxyapatite with the formation of nanometric crystal
agglomerates. Samples microbial activity evaluation with human saliva showed that pure HA has the effect of inhibiting microbial growth; CFU counting was observed to reduce. For the samples with antibiotic there was a CFU equal zero proving that the process used for gentamicin incorporation to the HA kept the antibiotic property of the material, and that the same was released during the tests.<br>A utilização de biomateriais remonta à antiguidade e recentemente as biocerâmicas têm sido fortemente investigadas como material para implantes ósseos. Dentre os
diferentes biomateriais a hidroxiapatita (HA) possui grande importância por ser um dos compostos que forma a fase mineral óssea. Assim, a HA tem sido amplamente estudada, especialmente pelo fato de ser um composto bioativo. A síntese de fosfatos de cálcio via precipitação apresenta vantagens como baixo custo e simplicidade, mas a maioria dos procedimentos descritos na literatura apresenta formação de produtos não estequiométricos e mistura de fases. Neste trabalho foi estudada a síntese de HA analisando a influência da concentração de gelatina no meio de precipitação nas características da hidroxiapatita obtida. Também foi
realizada a incorporação de gentamicina às amostras de HA obtidas e a análise do efeito antimicrobiano. A hidroxiapatita foi obtida através de precipitação em meio aquoso e gelatinoso, sendo posteriormente secada, peneirada e calcinada a 700ºC. Foram utilizadas as concentrações de gelatina de 1, 6, 10 e 60 g.L-1. Em seguida, foi efetuada a adição de sulfato de gentamicina na proporção de 1% em massa. As amostras foram caracterizadas por difração de raios X, distribuição do tamanho de partícula, área superficial específica pelo método BET, análise térmica,espectroscopia no infravermelho e microscopia eletrônica de varredura e
transmissão. A análise de DRX revelou a presença da fase de HA em todas as amostras e através do refinamento pelo método de Rietveld, verificou-se, para amostra obtida sem adição de gelatina, a presença de carbonato de cálcio, e HA
pura para amostra preparada em meio gelatinoso, indicando que a presença de gelatina estabilizou da fase hidroxiapatita. As análises FRX e EDS indicaram que a razão Ca/P ficou ligeiramente acima da esperada para obtenção de hidroxiapatita estequiométrica. A análise de distribuição granulométrica e área superficial pelo método BET indicaram diferenças no tamanho médio de aglomerados e na área
superficial do material relativas à síntese e ao processo de preparação das amostras para receber o antibiótico, o qual se processou com moagem em moinho de bolas. As análises de MEV e MET revelaram aspectos morfológicos e estruturais característicos da hidroxiapatita, observando-se formação de
aglomerados de cristais nanométricos. A avaliação da atividade microbiológica das amostras frente à saliva humana mostrou que a HA possui efeito inibidor no crescimento microbiano, tem sido observada redução na contagem de UFC. Para as amostras com a adição do antibiótico obteve-se contagem UFC igual a zero comprovando que o processo utilizado para incorporação da gentamicina na HA manteve a propriedade antibiótica do material, e que o mesmo foi liberado durante os testes.
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Lourenço, Felipe Rebello. "Doseamento microbiológico de gentamicina por difusão em agar - proposta de delineamento experimental." Universidade de São Paulo, 2006. http://www.teses.usp.br/teses/disponiveis/9/9139/tde-28032007-142656/.
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A gentamicina é um complexo antibiótico de largo espectro, produzido por actinomicetos do gênero Micromonospora e classificado entre os antibióticos aminoglicosídeos, utilizado no tratamento de infecções graves, devidas a microrganismos Gram-negativos. Alterações da sua atividade antimicrobiana, não demonstradas pelos ensaios químicos, podem ser avaliadas pelos ensaios microbiológicos. O objetivo deste trabalho foi comparar os delineamentos experimentais 5 x 1, 2 x 2 e 3 x 1, avaliando-se os parâmetros de validação de especificidade, linearidade, faixa ou intervalo, precisão e exatidão para cada delineamento experimental em diferentes níveis de concentração, apresentações e lotes. O plano de trabalho constituiu-se na realização de 81 ensaios (em 3 réplicas) de doseamento microbiológico de gentamicina. As concentrações das soluções empregadas foram preparadas numa faixa de 1,0 µg/mL a 5,0 µg/mL, diluídos em tampão fosfato 0,1 M pH 8,0. O meio utilizado foi o meio antibiótico no. 11, com Staphyloccocus epidermidis (ATCC 12228). Empregou-se 21 mL de meio como camada base e 4 mL de meio inoculado à 1% como camada superfície. As placas foram incubadas por 16-18 horas à 37 ± 1 °C. Os três delineamentos empregados apresentaram especificidade adequada para análise de creme dermatológico e solução injetável contendo sulfato de gentamicina. Também apresentaram exatidão e linearidade no intervalo avaliado. Os delineamentos não apresentaram diferença significativa quanto a precisão. Os resultados foram comparados através da determinação de índices de capacidade do sistema de medição. A análise estatística demonstrou que não há diferença significativa entre os resultados obtidos pelos delineamentos 5 x 1, 2 x 2 e 3 x 1, sendo equivalentes e intercambiáveis.<br>Gentamicin is a broad-spectrum antibiotic complex produced by actinomycetes belonging to Micromonospora genus and classified among aminoglycoside antibiotics, used in the treatment of serious infections derived from Gram-negative microorganisms. Alterations of their antimicrobial activity not shown in chemical assays can be evaluated through microbiological assays. The aim of this work was to compare 5 x 1, 2 x 2 and 3 x 1 experimental designs, evaluating validation parameters of specificity, linearity, range, precision, and accuracy for each experimental design in different levels of concentration, presentation, and lots. It consisted of 81 assays (in 3 replicas) of gentamicin microbiological dosage. The concentrations of the solutions used were employed in a range from 1.0 µg/ml to 5.0 µg/ml, diluted in phosphate buffer 0.1 M pH 8.0. Antibiotic medium number 11 was used, with Staphyloccocus epidermis (ATCC 12228)21ml of medium were used as base layer and 4 ml of medium inoculated at 1% were used as surface layer. The plates were incubated for 16-18 hours at 37 ± 1 ºC. The three designs employed showed adequate specificity for analysis of dermatological cream and injectable solution containing gentamicin sulphate. They also showed accuracy and linearity in the range evaluated, but not a significant difference concerning precision. The results were compared by means of the determination of the rates of measurement system capacity. The statistical analysis demonstrated that there is no significant difference among the results obtained.
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Matta, Roula. "Infections nosocomiales et résistance aux antibiotiques chez les bacilles à GRAM négatifs : étude de cohorte multicentrique dans les hôpitaux libanais." Electronic Thesis or Diss., Bordeaux, 2023. http://www.theses.fr/2023BORD0485.
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Les infections nosocomiales et la résistance bactérienne aux antibiotiques sont répandues au niveau mondial avec une prévalence plus élevée dans les pays en développement aux ressources limitées dont le Liban. Au Liban, les données épidémiologiques sur la résistance chez les bactéries à Gram négatif aux antibiotiques de dernier recours dans les hôpitaux et sur les infections nosocomiales sont rares. Objectifs : Nous avons conduit trois travaux visant à répondre aux objectifs suivants : une première étude pour identifier et comparer les différentes bactéries identifiées dans les infections communautaires et les infections nosocomiales, en mettant l'accent sur les comorbidités et les facteurs sociodémographiques associés. Puis deux études ciblant la résistance aux antibiotiques de dernier recours chez les bacilles à Gram négatif afin d’en décrire l’épidémiologie et d’identifier les caractéristiques des patients associées à cette résistance. La mortalité chez les patients porteurs d’un bacille à Gram négatif résistant aux carbapénèmes a été analysée. Méthodes. Le premier travail a consisté en une étude de cohorte rétrospective, multicentrique, menée dans cinq hôpitaux. Les données ont été recueillies à l'aide d'une fiche standardisée (données démographiques : genre et âge, maladies sous-jacentes et type d’infection acquise). Les deux autres études ont reposé sur une étude de cohorte prospective à partir d’une base de données constituée dans neuf hôpitaux libanais entre 2016-2017 (caractéristiques des patients, variables liées à l’hospitalisation et variables liées aux caractéristiques de l’infection). Les données ont été collectées et traitées avec Statistical Package for the Social Sciences SPSS, version 24. Des régressions logistiques ont été utilisées pour définir le profil des patients pour chaque type de résistance (céphalosporines de 3° génération- C3G, fluoroquinolones, aminosides, carbapénémes) observées chez les bacilles à Gram négatif (entérobactérales, Pseudomonas aeruginosa et Acinetobacter baumannii). Une analyse de sensibilité basée sur les résultats extrêmes des valeurs manquantes relatives à la sensibilité des bactéries a permis de prendre en compte les données manquantes et de fournir des résultats robustes. Résultats. La première étude a montré l’importance des bacilles à Gram négatif résistants aux antibiotiques au sein des infections nosocomiales mais aussi des infections communautaires avec deux facteurs indépendants de l’acquisition d’une infection nosocomiale : âge avancé et état d'immunosuppression. Les deux autres études ont montré des pourcentages de résistances élevées chez les bacilles à Gram négatif ciblés et ont permis d’établir différents profils de patients pour chaque type de résistance. Par exemple, pour Escherichia coli, la résistance aux C3G était associée à une admission antérieure à l’hôpital et à la présence d’une sonde urinaire. De la même façon, la résistance aux carbapénèmes chez les bacilles à Gram négatif était associée aux patients chirurgicaux, à la présence d’une sonde urinaire ainsi qu’à une infection pulmonaire ou du site opératoire. Concernant la mortalité globale, le modèle proportionnel de Cox a montré que la résistance aux carbapénèmes était associée à une différence significative en termes de survie hospitalière chez les patients porteurs de bacilles à Gram négatif non fermentants par rapport aux bactéries sensibles. Conclusions. Nous avons rapporté la résistance aux antibiotiques de derniers recours chez les entérobactérales (E. coli et entérobactérales non- E. coli) et les bacilles à Gram négatif non fermentants identifiées dans des hôpitaux libanais où les données épidémiologiques sont rares. La description des profils de patients porteurs de ces souches bactériennes résistantes permettra aux cliniciens de prescrire une antibiothérapie probabiliste adaptée<br>Hospital-acquired infections and bacterial resistance to antibiotics are widespread worldwide, with a higher prevalence in developing countries with limited resources, including Lebanon. In Lebanon, epidemiological data on resistance among Gram-negative bacteria to antibiotics of last resort in hospitals and on nosocomial infections are scarce. Aims: We conducted three studies to meet the following objectives: a first study to identify and compare the different bacteria identified in communityacquired infections and nosocomial infections, focusing on associated co-morbidities and sociodemographic factors. This was followed by two studies targeting resistance to last-resort antibiotics in Gram-negative bacilli, in order to describe the epidemiology and identify patient characteristics associated with this resistance. Mortality in patients with Gram-negative bacilli resistant to carbapenems was analyzed. Methods. The first study was a retrospective, multicenter cohort study conducted in five hospitals. Data were collected using a standardized form (demographic data: gender and age, underlying diseases and type of acquired infection). The other two studies were based on a prospective cohort study using a database compiled in nine Lebanese hospitals between 2016 and 2017 (patient characteristics, variables related to hospitalization and variables related to the characteristics of the infection). Data were collected and processed using Statistical Package for the Social Sciences SPSS version 24. Logistic regressions were used to define the profile of patients for each type of resistance (3rd generation cephalosporins-3GC, fluoroquinolones, aminoglycosides, carbapenem) observed in Gram-negative bacilli (Enterobacteria, Pseudomonas aeruginosa and Acinetobacter baumannii). A sensitivity analysis based on the extreme results of the missing values for bacterial sensitivity was used to take account of the missing data and provide robust results. Results. The first study showed the importance of Gram-negative bacilli resistant to antibiotics in both hospital and community-acquired infections, with two independent factors in the acquisition of a nosocomial infection: advanced age and immunosuppression. The other two studies showed high percentages of resistance in the targeted Gram-negative bacilli and established different patient profiles for each type of resistance. For example, in Escherichia coli, resistance to 3GC was associated with previous hospital admission and the presence of a urinary catheter. Similarly, resistance to carbapenems in Gram-negative bacilli was associated with surgical patients, the presence of a urinary catheter, and pulmonary or surgical site infection. In terms of overall mortality, the Cox proportional model showed that carbapenem resistance was associated with a significant difference in hospital survival in patients with nonfermenting gram-negative bacilli compared with susceptible bacteria. Conclusions. We report on resistance to antibiotics of last resort in enterobacteria (E. coli and Non-E. coli enterobacterales) and non-fermenting Gram-negative bacilli identified in Lebanese hospitals, where epidemiological data are scarce. Describing the profiles of patients carrying these resistant bacterial strains will enable clinicians to prescribe appropriate probabilistic antibiotic therapy
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Bacon, Joanna. "Gentamicin resistance in Micromonospora purpurea." Thesis, University of Leicester, 1999. http://hdl.handle.net/2381/29634.
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The gene, grmA, from the gentamicin producer Micromonospora purpurea, confers high level resistance to gentamicin and kanamycin. The ribosomes of M. purpurea are constitutively resistant to these antibiotics by modification of the 16S rRNA in the 30S subunit. grmA encodes a methyltransferase. In this study, reverse transcriptase assays confirmed that GrmA methylated the 16S rRNA at residue G1389 in S. lividans. However these assays also revealed that G1389 was not methylated in M. purpurea, indicating that grmA is silent in its native host. grmA, driven by a constitutive promoter (ermEp*), was introduced into M. purpurea by conjugal transfer with the hope that the effects of a putative repressor would be titrated out by the expression of an extra copy of the gene. Changes in the level of grmA transcript and methylation of the 18S rRNA were subsequently observed. RNA hybridisation analysis revealed that grmA was transcribed in the wild type strain of M. purpurea, and that the transcript was probably full length. There was a higher level of grmA transcript in S. lividans containing the gene than in M. purpurea, suggesting that grmA was transcriptionally regulated in M. purpurea but not in S. lividans. The extra copy of grmA in M. purpurea was expressed efficiently from ermEp*. However, 16S rRNA extracted from this strain, had not been methylated at G1389, although the transcriptional control of grmA was apparently alleviated. These data suggested that there may have been more than one control mechanism regulating the expression of grmA. If grmA is not expressed in M. purpurea, there must be another resistance gene responsible for the constitutive phenotype being expressed. Despite attempts to isolate alternative gentamicin resistance genes from M. purpurea, only grmA was found.
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Perez, Paula Spanopoulos 1987. "Efeitos do tratamento com gentamicina na recuperação da distrofina e na regeneração muscular em camundongos mdx." [s.n.], 2013. http://repositorio.unicamp.br/jspui/handle/REPOSIP/317582.
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Orientador: Humberto Santo Neto<br>Dissertação (mestrado) - Universidade Estadual de Campinas, Instituto de Biologia<br>Made available in DSpace on 2018-08-23T08:31:35Z (GMT). No. of bitstreams: 1
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Previous issue date: 2013<br>Resumo: O resumo poderá ser visualizado no texto completo da tese digital<br>Abstract: The abstract is available with the full electronic document<br>Mestrado<br>Biologia Celular<br>Mestra em Biologia Celular e Estrutural