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  • About
  • The Global ETD Search service is a free service for researchers to find electronic theses and dissertations. This service is provided by the Networked Digital Library of Theses and Dissertations.
    Our metadata is collected from universities around the world. If you manage a university/consortium/country archive and want to be added, details can be found on the NDLTD website.
121

Caracterização das mutações envolvidas na resistência de isolados de Mycobacterium tuberculosis à estreptomicina e sua relação com o sistema de efluxo / Characterization of mutations involved in resistance to streptomycin in clinical isolates of Mycobacterium tuberculosis and its relation with the efflux system

Spies, Fernanda Sá January 2007 (has links)
O Mycobacterium tuberculosis é intrinsecamente resistente a diversos antimicrobianos. Esta resistência é devida, principalmente, ao envelope hidrofóbico da célula bacteriana que atua como uma barreira efetiva para diversos compostos. Outros determinantes da sua resistência intrínseca incluem enzimas hidrolíticas e bombas de efluxo de drogas. A resistência adquirida em isolados clínicos de M. tuberculosis é principalmente devida a mutações em genes que codificam alvos para os fármacos ou em seus ativadores. Apesar disso, um número entre 5–30% das cepas resistentes não têm caracterizado o seu mecanismo de resistência, considerando-se o sistema de efluxo como uma das possibilidades para esta resistência. O efluxo é o resultado da atividade de proteínas transportadoras envolvidas na extrusão de substâncias (incluindo todas as classes de relevantes antimicrobianos clínicos) de dentro da célula para o meio externo. O principal objetivo deste trabalho foi comparar a Concentração Mínima Inibitória (CMI) em condições de diferentes tratamentos (presença e ausência de inibição do sistema de efluxo) e os resultados obtidos com o seqüenciamento dos genes rpsL e rrs. Para isso foram testados 79 isolados de M. tuberculosis, destes, 43 (54%) isolados apresentaram mutações; 38 (48%) diminuíram a CMI na presença de inibidores do sistema de efluxo, sendo que isso ocorreu tanto em isolados resistentes ou sensíveis, mutados ou não-mutados. Em três isolados resistentes a estreptomicina não foram identificadas alterações nos genes rpsL e rrs e na presença de inibidores do sistema de efluxo a resistência foi diminuída. A diminuição da CMI nesses isolados resistentes, embora sem mutação, indica uma possível participação do sistema de efluxo. Nas cepas mutadas, o mecanismo de efluxo, estaria aumentando a tolerância do isolado à concentração da droga. Estas últimas possuiriam dois mecanismos de resistência atuantes (mutação nos genes alvo do fármaco e superexpressão das proteínas de membrana responsáveis pelo efluxo de drogas). / Mycobacterium tuberculosis is naturally resistant to many antimicrobials. This resistance is due mainly to the hydrophobic cell envelope acting as an effective permeability barrier for many compounds. Other determinants ones of its intrinsic resistance include hydrolytic enzymes and efflux pumps of drugs. The acquired resistance in clinical isolates of M. tuberculosis is mainly due to mutations in genes that encode targets for drugs substances or in their activators. Even so, in 5-30% of the resistant strains the resistance mechanism is not known and the efflux system has been considered as one of the possibilities for this resistance. Efflux is the result of the activity of transport proteins involved in extrusion of substances (including all classes of clinically relevant antimicrobials) from the interior of the cells into the external environment. The main goal of this study is to compare the Minimal Inibitory Concentration (MIC) in different conditions (with or without efflux system inhibitors) and the sequencing data of the rpsL and rrs genes. For that we have analized 79 M. tuberculosis isolates, and from these, 43 (54%) presented mutations; 38 (48%) decreased the MIC in presence of efflux system inhibitors. This decrease in MIC occurred in resistant or sensitive isolates, with or without mutations. Three resistant isolates did not present any mutations in rpsL and rrs genes and in presence of efflux system inhibitors the resistance decreased. The decrease of MIC in these resistant isolates, although without mutation, indicates participation of the efflux system. In the mutated isolates the efflux system could increase the tolerance to drug concentration. In these isolates two resistance mechanisms must be acting (mutation on the drug target genes and over-expression of membrane proteins responsible for the drug efflux).
122

Polymorphism and structural studies of isoniazid derivatives

Hean, Duane 21 May 2015 (has links)
A Dissertation submitted to the Faculty of Science, University of the Witwatersrand, Johannesburg, in fulfilment of the requirements for the degree of Master of Science. 21 May 2015 / Crystal polymorphism is the capacity of a solid crystalline form to exist in more than one structural arrangement. In the pharmaceutical setting investigations into the polymorphic forms of potential drugs are of vital importance since different crystalline forms can affect bioavailability, mechanical, thermal, and chemical properties. One such example is isonicotinic acid-(1-phenylethylidene) hydrazide (IPH), a derivative of the popular drug isoniazid (used as first line treatment against Mycobacterium tuberculosis) was found to crystallise in six different polymorphic forms. Each crystal structure was determined using X-ray diffraction techniques and including the thermal phase relationships of the polymorphic compound were delineated. In addition to polymorph elucidation, isonicotinic acid-(1-phenylethylidene) hydrazide was modified with –OH and –NH2 at various aromatic positions, creating geometric pyridyl isomers. In-depth studies of these pyridyl isomers revealed a diverse range of supramolecular aggregates. Preliminary thermal screening suggests that only a small selection of these pyridyl isomers present potential polymorphic activity for further study.
123

Regulation and trafficking of the iron export protein, ferroportin1, in Mycobacterium tuberculosis-infected macrophages

Van Zandt, Kristopher Edward, January 2007 (has links)
Thesis (Ph. D.)--Ohio State University, 2007. / Title from first page of PDF file. Includes bibliographical references (p. 93-119).
124

The role of alpha 4 beta 1 integrin (VIa-4) in recruitment of mycobacterium tuberculosis-specific TH1-LIKE recall responses to the human lung

Walrath, Jessica R. January 2007 (has links)
Thesis (M.S.)--Case Western Reserve University, 2007. / [School of Medicine] Department of Pathology. Includes bibliographical references.
125

Structural and Functional Studies of Mycothiol Biosynthesis Precursor Enzyme in Mycobacterium tuberculosis

Zhu, Wan Wen 2011 August 1900 (has links)
MshA is a glycosyltransferase that synthesizes the precursor of mycothiol, a low-molecular-weight thiol found exclusively in Actinomycetes, including the virulent pathogen Mycobacterium tuberculosis (Mtb). The structure of MshA from Mtb (herein coined as TbMshA) and its complex with uridine diphosphate N-acetyl-glucosamine (UDP-GlcNAc) have been solved to resolutions of 2.32 A and 2.89 A respectively. Both structures form two monomers in the asymmetric unit cell and exhibit typical beta/alpha/beta Rossmann folds. Upon binding of UDP-GlcNAc, the C-terminal domain of TbMshA undergoes conformational changes in order to interact with UDP-GlcNAc at the binding site. In addition, ligand-bound TbMshA structure enables the identification of critical residues for enzymatic interactions, especially the residue Glu-353 (E353) at the active site that is believed to serve as a nucleophile in the sugar transfer of TbMshA. In order to verify this, a mutant of TbMshA with a single amino acid mutation from glutamate to glutamine at residue 353 is generated. The mutant (E353Q) has shown reduced enzyme activity by more than four-fold compared to the wild-type TbMshA (Vmax for wild-type is 0.17 plus/minus 0.02 microM sec^-1, whereas Vmax for E353Q is 0.04 plus/minus 0.01 microM sec-1). The kcat/Km for wild-type TbMshA (3.5 plus/minus 1.1 * 10^3 M^-1 sec^-1) is an order of magnitude higher than that of the mutant (0.3 plus/minus 0.1 * 10^3 M^-1 sec^-1), indicating the catalytic efficiency is greatly suppressed by the mutation. Mass spectrometry data also reveals that E353Q is unable to form the product of the reaction catalyzed by the wild-type TbMshA. These findings suggest the important role of Glu-353 in the structure and activity of TbMshA.
126

Relaciones filogenéticas entre algunos Telmatobinidos (Anura, Leptodactylidae, Telmatobiinae) de Perú basado en la morfología de los estados larval y adulto

Pandia Fajardo, Elma Alcira January 2006 (has links)
La finalidad del presente estudio fue evaluar el medio de cultivo Löwenstein - Jensen modificado con nitrato de potasio (KNO3) para el diagnóstico de Mycobacterium tuberculosis, compararando la sensibilidad y especificidad de este medio modificado con el medio Löwenstein - Jensen convencional y evaluando los factores importantes que influyen en el proceso como por ejemplo el tiempo. En el presente estudio, se evaluó un total de 120 muestras provenientes de pacientes diagnosticados con tuberculosis pulmonar por baciloscopía, las muestras (esputo, lavado bronquial, aspirado bronquial, aspirado gástrico) se trataron por el método Petroff modificado para su descontaminación y homogenización y se sembraron en los medios Löwenstein - Jensen convencional y modificado con nitrato de potasio al 35%. Luego estos cultivos fueron incubados a 37°C durante 7,10, 14 días, después de los cuales se determinó la reducción de nitratos a nitritos. El nitrito producido por Mycobacterium tuberculosis permitió identificar la presencia de la bacteria empleando el reactivo de Peter Griess, detectado por medio de un viraje de color del medio de cultivo. En el medio Löwenstein - Jensen modificado, se determinó que la sensibilidad era del 41% y la especificidad del 100%, con un valor predictivo positivo de 100%, y valor predictivo negativo de 34%. Al comparar estadísticamente la sensibilidad y especificidad de la prueba en el medio modificado y el cultivo convencional o Estándar de oro, se observó que los factores predominantes en el proceso de evaluación son: tipo (esputo, lavado bronquial, aspirado bronquial, aspirado gástrico) y calidad de la muestra (Carga Bacilar), obtenidas adecuadamente. Los resultados fueron obtenidos en su mayoría a los 10 días, con un promedio ponderado de 12 días para el diagnóstico de Mycobacterium tuberculosis. El estudio realizado justifica el empleo del medio Löwenstein - Jensen modificado conteniendo nitrato de potasio (KNO3), presentándose como una alternativa para el diagnóstico presuntivo de Mycobacterium tuberculosis. / The tuberculosis in anyone of his manifestations, one becomes of without a doubt the public- health problems more important at the present time and it has been a diagnostic shoot's quest and it is, one join of the objective main things in many parts worldly, most of all in countries as the our that he presents high incidence rates and whose more population once was affected does not count on the economic means to accede to anyone of the diagnostic- shoot methods existents. The present study's purpose was to evaluate Löwensein-Jensen's midway modified with nitrate reductasa in order to the pulmonary tuberculosis's diagnosis, Mycobacterium tuberculosis's identification, comparing sensibility and modified specificity of this midway with the cultivation conventional Löwenstein-Jensen and evaluating the mains factors that have influence in the process for example theTime. In the present study evaluated 120 samples coming from patients diagnosed with pulmonary tuberculosis for baciloscopy; the samples them tried to him for the method Petroff once was modified in order to his decontamination and homogenization before being sown in the Löwensein-Jensen's midway conventional and modified , with potassium nitrate to 37 per cent.. The cultures were incubates went to 37 ºC for 7, 10, 14 days; then the nitrate reduction was suggesting growth to nitrite. To positive reaction was detected by means of a color turn. In the Löwensein-Jensen's midway conventional obtained a sensibility of 41 per cent and specificity of 100 per cent in the Löwenstein-Jensen midway modificated, with a positive value once of 100 per cent and negative value once of 34 per cent. To the comparing statistically sensibility and specificity of the essay test with nitrate reductasa and the conventional cultivation or Gold Standard heeded that the prevailing factors in the evaluation process are: the type and quality of the sample quality (charges Bacilar), fitting to obtain. The results were obteined aftermaths in the main to the 10 days, with a 12 days average prudent in order to TB'S diagnosis – Pulmonar The study once was accomplished justifies test's job Löwenstein – Jensen modified with potassium of Nitrate (KNO3), encountering as an alternative in order to the Mycobacterium tuberculosis's diagnosis.
127

Étude de la tuberculose chez l'éléphant importance en parc zoologique /

Delnatte, Pauline Ducos de Lahitte, Jacques January 2008 (has links) (PDF)
Reproduction de : Thèse d'exercice : Médecine vétérinaire : Toulouse 3 : 2008. / Titre provenant de l'écran titre. Bibliogr. p. 207-217.
128

Molecular characterization of isoniazid-resistant mycobacterium tuberculosis in Hong Kong

Woo, Wai-lan., 胡慧蘭. January 2005 (has links)
published_or_final_version / Medical Sciences / Master / Master of Medical Sciences
129

Direct detection of rifampin-resistant mycobacterium tuberculosis in clinical specimens by DNA sequencing

梁秀敏, Leung, Sau-man. January 2001 (has links)
published_or_final_version / Medical Sciences / Master / Master of Medical Sciences
130

Protein-ligand interactions of arylamine N-acetyltransferase from Mycobacterium smegmatis

Brooke, Edward W. January 2003 (has links)
Tuberculosis is the world's largest cause of death from an infectious agent. Treatment is by an extended period of combination chemotherapy. Drug resistance is an increasing problem in tuberculosis therapy, particularly to the frontline anti-tubercular drug isoniazid (INH). Recombinant arylamine N-acetyltransferase (NAT) of Mycobacterium tuberculosis N-acetylates INH using the cofactor Acetyl Coenzyme A. NAT from M. tuberculosis is a polymorphic enzyme and also acetylates INH in vivo. Acetylated INH is inactive therapeutically against M. tuberculosis both in vivo and in vitro. The acetylation of isoniazid in the mycobacterial cell may compete with the activation of INH by the catalase-peroxidase, katG, and hence contribute to INH resistance in clinical isolates. Inhibition of NAT in M. tuberculosis may thus increase the efficacy of INH therapy. A novel assay based around the detection of free Coenzyme A released during the acetylation reaction was used to determine the substrate specificity of recombinant NAT from the related Mycobacterium M. smegmatis (MSNAT). A relationship was observed between the lipophilicity of simple arylamine substrates and the rate of acetylation by MSNAT. Several MSNAT substrates possess antibacterial activity. The assay could also be used to screen compound libraries for MSNAT inhibitors. Synthesis of seventeen thiazolidinedione sultams in collaboration with Dr.Vickers (Dyson Perrins), identified as weak inhibitors of MSNAT, gave a minimum competitive inhibitory constant of 14μM. Screening a library of 5,074 drug-like compounds for inhibition of MSNAT identified thirteen compounds with semi-maximal inhibition constants (IC<sub>50</sub>) of below 10μM. Based on this, fifteen maleimides were synthesised and were irreversible inhibitors of MSNAT with submicromolar potency. Similarly, ninety-six aminothiazoles were synthesised by Dr. Vickers and were uncompetitive inhibitors of MSNAT with a minimum IC<sub>50</sub> of 1.5μM. The most potent aminothiazole showed no effect on the growth of M. smegmatis or M. bovis BCG or the sensitivity of the bacteria to isoniazid. However the aminothiazoles were shown not to penetrate the cells.

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