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Preparation of Pyridinium Derivatives of 2,3-Dichloro-5(8?)-Nitro-1,4-NaphthoquinoneMahon, Frank 08 1900 (has links)
This paper describes the preparation of pyridine derivatives of 2,3-dichloro-5(8?)-nitro-1,4-naphthoquinone. A method for the nitration of 2,3-dichloro-1,4-naphthoquinone is also described. Certain 4-n-alkyl, 3,4-dialkyl, and 4-cycloalkyl pyridine derivatives are caused to undergo condensation reactions with the nitrated naphthoquinone, giving rise to a series of compounds of the preceding type (X). All of the compounds prepared will be tested for anti-tubercular activity by Parke-Davis and Company.
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Derivatives of SulfonamideZachry, David R. 08 1900 (has links)
This thesis describes experiments in creating derivatives of sulfonamide. The derivatives were then submitted for testing for anti-tubercular activity.
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The Preparation of Pyridinium Derivatives by the Knoevenagel CondensationMiller, Eugene James 05 1900 (has links)
An attempt is made in the work described in this paper to extend the series started by Hall and Platas by means of a Knoevenagel condensation between 3-hydroxy-1,4-naphtho-quinone-2-(4-methylpyridinium) anhydride and various aromatic aldehydes giving rise to a series of unsaturated substituents on the four position of the pyridine ring.
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Molecular biological characterisation of the novel Rifampicin inactivation mechanism in Nocardioform bacteriaAndersen, Susan Jean January 1996 (has links)
Rifampicin is one of the major antibiotics used in the treatment of Mycobacterium tuberculosis. This organism causes tuberculosis. Other related nocardioform bacteria which include the Rhodococci are opportunistic pathogens in AIDS patients. These organisms cause tuberculosis-like disease and are currently treated with rifampicin and other drugs. The presence of a low level rifampicin resistance mechanism was identified in seven rhodococcal strains and five other related and unrelated bacteria. Abbreviated Abstract. Open document to view full version] / GR2017
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Drug-resistant Mycobacterium tuberculosis in Estonia /Krüüner, Annika, January 2003 (has links)
Diss. (sammanfattning) Stockholm : Karol. inst., 2003. / Härtill 6 uppsatser.
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The pharmacokinetics and toxicity of antituberculosis agents and other co-administered drugs in children with tuberculosis, with and without HIV infection, and their relationship to nutritional statusCilliers, Karien 03 1900 (has links)
Thesis (MNutr)--University of Stellenbosch, 2011. / ENGLISH ABSTRACT: Problem definition: Malnutrition increases the incidence and exacerbates the clinical manifestations of TB. Hepatotoxicity is one of the most serious and most frequent side-effects of anti-tuberculosis drugs and may be three times higher in malnourished patients.
Objective: The influence of nutritional and retroviral status on the bio-availability and toxicity of anti-tuberculosis agents was studied and a possible relationship between abdominal lymph node enlargement and the occurrence of malnutrition investigated.
Subjects and setting: The study subjects were 53 children, 19 HIV-infected and 34 HIV-uninfected, aged 3 months to 13 years with probable or confirmed tuberculosis admitted to the paediatric ward of Brooklyn Hospital for Chest Diseases in Cape Town, South Africa. The nutritional status of the children was assessed over the first four months of tuberculosis treatment by nutrient intake, anthropometric status and biochemical parameters. The relationship between abdominal lymph node enlargement and the occurrence of malnutrition was also evaluated. Pharmacokinetic studies were performed to evaluate the bio-availability of anti-tuberculosis agents and drug hepato-toxicity was evaluated by liver function.
Results: Stunting (46.27%) and underweight (34.51%) were the most common types of malnutrition in the children studied. HIV-infection did not have a significant effect on stunting or wasting, but had a significant effect (p=0.003) on underweight for age with 31.5% HIV-infected compared to 2.9% HIV-uninfected at enrolment, but the effect was not statistically significant at month 4. There was no change in the number of stunted, wasted or underweight children from enrolment after 1 month of treatment to month 4 of treatment.
HIV-infection did not have a significant effect on abdominal TB involvement (p=0.43354), and nutritional status was not significantly affected by abdominal lymph-node involvement.
At enrolment weight for age had a significant effect on AST and ALT with p-values of 0.02166 and 0.02765 respectively and wasting had a significant effect on GGT at enrolment (p=0.03014). However on enrolment only two HIV-infected and two HIV-uninfected children had ALT values increased >X2 normal. Similarly AST values >X3 normal were found in only one HIV-infected child and two HIV-uninfected children. Stunting did not significantly affect liver enzymes. Anthopometric status did not have a significant effect on liver enzymes at month 4.
None of the parameters used to determine nutritional status had a statistically significant effect on INH-levels or RMP-levels.
HIV-infection had a significant negatve effect on selenium (p=0.030 and 0.012) and ferritin (p=0.026 and 0.002) at enrolment and month 4 and on IBC (p=0.025) at enrolment. At month 4 HIV-infection had a significant negative effect on the mean vitamin C-levels (p=0.005).
Conclusions: HIV co-infection did not affect the extent or distribution of body composition changes in this study. Stunting was the most prevalent form of malnutrition in the study group, indicating longstanding undernutrition, which may be due to factors other than the present TB infection. Appropriate treatment of tuberculosis did not appear to affect the nutritional status over the four month period of the study. / AFRIKAANSE OPSOMMING: Probleemstelling: Wanvoeding verhoog die insidensie en vererger die kliniese beeld van TB. Hepatotoksisiteit is een van die ernstigste en algemeenste newe-effekte van anti-tuberkulose middels en mag tot drie keer hoër wees in wangevoede pasiënte.
Doelwit: Die invloed van die kinders se voedings- en retrovirale status op die bio-beskikbaarheid en toksisiteit van anti-tuberkulose middels was ondersoek en 'n moontlike verband tussen vergrote abdominale limfnodes en die voorkoms van wanvoeding was ondersoek.
Deelnemers en omgewing: Die deelnemers aan die studie was 53 kinders, 19 HIV-positief en 34 HIV-negatief, tussen die ouderdomme van 3 maande en 13 jaar met moontlike of bevestigde tuberkulose toegelaat tot die pediatriese saal van Brooklyn Hospitaal vir Borskwale in Kaapstad, Suid Afrika. Die voedingstatus van die kinders was bepaal oor die eerste vier maande van tuberkulose behandeling ten opsigte van nutriëntinname, antropometriese status en biochemiese parameters. Die verhouding tussen vergrootte abdominale limfnodes en die voorkoms van wanvoeding was ook geëvalueer. Farmakokinetiese studies was uitgevoer om die bio-beskikbaarheid van anti-tuberkulose middels te evalueer en hepatotoksisiteit was deur lewerfunksie geëvalueer.
Resultate: Dwerggroei (46.27%) en ondergewig (34.51%) was die algemeenste tipes wanvoeding teenwoordig by die kinders bestudeer. HIV-infeksie het nie 'n noemenswaardige effek op dwerggroei of uittering gehad nie, maar het wel 'n noemenswaardige effek (p=0.003) getoon op ondergewig vir ouderdom met 31.5% HIV-positief vergeleke met 2.9% HIV-negatief by inskrywing, wat nie statisties noemenswaardig was teen maand 4 nie. Daar was geen verandering in die hoeveelheid kinders met dwerggroei, uittering of ondergewig vanaf inskrywing na 1 maand van behandeling tot maand 4 van behandeling nie.
HIV-infeksie het nie 'n noemenswaardige effek op abdominale TB gehad nie (p=0.43354), en vergrootte abdominale limfnodes het nie 'n noemenswaardige effek op voedingstatus gehad nie.
By inskrywing het gewig vir ouderdom 'n noemenswaardige effek op AST en ALT gehad met p-waardes van 0.02166 en 0.02765 onderskeidelik en uittering het 'n noemenswaardige effek op GGT by inskrywing gehad (p=0.03014). Dwerggroei het nie die lewerensieme noemenswaardig beïnvloed nie. Antropometriese status het nie 'n noemenswaardige effek op lewerensieme teen maand 4 gehad nie.
Geen van die parameters wat gebruik is om voedingstatus te bepaal het 'n noemenswaardige statistiese effek op INH-vlakke of RMP-vlakke gehad nie.
HIV-infeksie het 'n noemenswaardige effek op selenium (p=0.030 en 0.012) en ferritien (p=0.026 en 0.002) by inskrywing en maand 4 gehad en op IBC (p=0.025) by inskrywing. HIV-infeksie het 'n statisties noemenswaardige effek op die gemiddelde vitamien C-vlakke (p=0.005).
Gevolgtrekking: HIV ko-infeksie het nie die verspreiding of mate van liggaamsamestelling veranderinge in hierdie studie geaffekteer nie. Dwerggroei was die algemeenste vorm van wanvoeding in die studiegroep, wat langstaande wanvoeding aandui en toegeskryf mag word aan faktore buiten die huidige TB infeksie. Toepaslike tuberkulose behandeling het nie 'n wesenlike effek op voedingstatus gehad tydens die vier maande periode van die studie nie.
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Fatores de risco associados às reações adversas a medicamentos antituberculose : uma revisão sistemáticaResende, Laíse Soares Oliveira 28 August 2013 (has links)
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tese_6767_2011_Laise.pdf: 1611120 bytes, checksum: dc3f71b886d62aa108232580c6306fb6 (MD5) / Introdução: Os problemas relacionados à interrupção e ao abandono do tratamento da tuberculose culminam em aumento da morbimortalidade. A ocorrência de reações adversas a medicamentos (RAM) é apontada como um dos principais fatores relacionados. Objetivo: Identificar evidência científica disponível sobre os fatores de risco associados às reações adversas decorrentes do uso de medicamentos antituberculose. Métodos: Trata-se de uma revisão sistemática em que se buscou estudos sobre fatores de risco associados às reações adversas aos medicamentos antituberculose nas bases Medical Literature Analysis and Retrieval System Online (MEDLINE), no período entre 1965 e 2013 e Literatura Científica e Técnica da América Latina e Caribe (LILACS), no período entre 1982 e 2013. Localizou-se 1389 artigos que passaram por uma triagem a partir da leitura dos títulos e resumos. A partir dessa análise, selecionou-se 85 estudos para serem lidos na íntegra. Ao final, 16 estudos foram incluídos na análise a partir dos critérios de elegibilidade adotados em cada etapa, que tiveram seus dados extraídos para os cálculos de Qui-quadrado, Mantel-haenszel, Odds ratio simples (OR) e combinada (ORc). Resultados: Os fatores de risco significantes para o desenvolvimento de RAM foram: idade (maior que 60 anos), esquemas de tratamento, alcoolismo, anemia, coinfecção pelo vírus da imunodeficiência humana ou vírus da hepatite, polimorfismo da N-acetiltransferase 2 (acetilador lento), além da deficiência de sódio, ferro e albumina. Enquanto as meta-análises evidenciaram que os fatores de proteção das RAM hepáticas são: sexo masculino (ORc=0,38; IC95%=0,20-0,72), idade >35 anos (ORc=0,38; IC95%=0,20-0,72), fenótipo acetilador rápido/intermediário da N-acetiltransferase 2 (ORc=0,41; IC95%=0,18-0,90). Conclusões: Há evidências para subsidiar o manejo de RAM antituberculose nos serviços de saúde pública. / Setting: The problems related to the interruption and the dropout of tuberculosis treatments lead to increased morbi-mortality. Drugs adverse effects are some of the main related reasons. Objective: To identify scientific evidence available about risk factors associated to adverse effects due to antituberculosis drugs usage. Design: A systematic review of studies about risk factors related to adverse effects of antituberculosis drugs selected in MEDLINE database from 1965 to 2013 and in LILACS database from 1982 to 2013. After screening papers by reading all titles and abstracts there were 1.389 approved papers. Based on this analysis, 85 papers were selected to be fully read. At the end, 16 papers were selected to be analyzed due to the eligibility criteria on each step, had their data extracted for calculation of Chi-square, Mantel-Haenszel, Odds ratio (OR) and combined Odds ratio (ORc). Results: Significant risk factors to the development of drugs adverse effects were: age over 60 years, treatment regimen, alcoholism, anemia, coinfection by human immunodeficiency or hepatitis viruses, phenotype slow acetylators of N-acetyltransferase 2 and the deficiency of sodium, iron and albumin. While, meta- analysis showed that protective factors of liver AED are: male (ORc = 0.38, 95%CI= 0.20 to 0.72), age > 35 years (ORc=0.38, CI95%=0.20 to 0.72), acetylator phenotype fast / intermediate of N-acetyltransferase 2 (ORc=0.41, 95% I= 0.18 to 0.90). Conclusion: There is evidence to support the management of antituberculosis AED in public health services.
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Naphthoquinone StudiesPadgett, William A. 08 1900 (has links)
This thesis describes a series of naphthoquinone reactions employing pyridine carboxylic acid derivatives (nicotinic acid derivatives). The products of these reactions will be tested by Parke, Davis and Company for their activity against the tubercle bacillus and other pathogenic microorganisms.
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The Attempted Synthesis of some Heterocyclic SulfonesCompton, William David 08 1900 (has links)
This thesis describes two experiments: one related to antihistamines, and the other related to antitubercular compounds.
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Construction d’un modèle thérapeutique mathématique de la tuberculose pulmonaire : aspects pharmacocinétiques, pharmacodynamiques, physiopathologiques et premier modèle du traitement par la rifampicine / A mathematical model of pulmonary tuberculosis disease and treatment : pharmacokinetic, pharmacodynamic, and physiological aspects of a first model of rifampin therapyGoutelle, Sylvain 30 November 2009 (has links)
L’un des défis actuels de la lutte contre la tuberculose est de développer un traitement plus court et plus efficace. La modélisation mathématique constitue une approche qui peut nous aider à comprendre les problèmes actuels et favoriser les innovations thérapeutiques. L’objectif de ce travail est de construire un modèle thérapeutique mathématique de la tuberculose pulmonaire basé sur des éléments pharmacocinétiques, pharmacodynamiques et physiopathologiques. La mise en application du modèle pharmacodynamique a été précédée d’une étude théorique sur l’équation de Hill. Cette synthèse a permis de dégager les bases rationnelles de son utilisation en modélisation pharmacologique. En utilisant une approche de population, un modèle pharmacocinétique de diffusion pulmonaire a permis de décrire les concentrations en rifampicine dans le plasma et le poumon chez 34 sujets. Le modèle a ensuite été utilisé pour analyser la valeur d’indices pharmacodynamiques corrélés à l’effet chez 10 000 sujets fictifs, par simulation de Monte Carlo. Les résultats indiquent que la dose de standard de rifampicine conduit à des concentrations globalement peu efficaces et pouvant favoriser la résistance bactérienne. Un premier modèle mathématique du traitement de la tuberculose par la rifampicine, incluant un modèle physiopathologique formel, a enfin été construit. Il permet de simuler la dynamique bactérienne du premier jour de l’infection au dernier jour de traitement. L’ensemble des résultats conduit à une remise en question de la dose standard de rifampicine et suggère une nouvelle hypothèse sur les causes de la persistance de Mycobacterium tuberculosis au cours du traitement antituberculeux / There is a critical need for a shorter tuberculosis treatment to improve tuberculosis control. Mathematical models may be helpful to understand current problems associated with tuberculosis therapy and to suggest innovation resources. The objective of this study is to set up a full mathematical model of tuberculosis treatment by rifampin, based on pharmacokinetic, pharmacodynamic and physiological submodels. Prior to its application in the pharmacodynamic modeling framework, the Hill equation has been the focus of a theoretical study. The various properties of this equation have been reviewed and the rationale of its use in pharmacological modelling has been clarified. Rifampin pharmacokinetics in plasma and lungs was modelled in a population of 34 volunteers by use of a nonparametric population approach. Then, a 10,000 subject Monte Carlo simulation was performed to explore Mycobacterium tuberculosis killing effect and prevention of resistance by rifampin. The results suggest that rifampin pulmonary concentrations obtained with the standard dose are too low to be highly effective and prevent drug resistance in most subjects. Finally, a full mathematical model of tuberculosis treatment, including a physiological model, has been implemented. The model is able to simulate the time-course of bacterial counts from the first day of infection to the last day of treatment. Overall results of this modelling effort indicate that current dosage regimens of rifampin may be optimized. In addition, this work suggests a new hypothesis regarding the bacterial persistence during tuberculosis treatment.
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