RESUMO
Mycobacterium leprae strains from Indian leprosy patients were analyzed using the six base tandem repeat, GACATC, in rpoT gene as genetic marker. DNA was extracted from slit-skin smears and nasal swabs of new untreated as well as treated leprosy patients living in different regions of India. PCR amplification of rpoT gene and sequencing of amplicons showed the presence of two genotype of M. leprae in this study, 73.4% having three copies (ancient Indian type) and 26.6% contain 4 copies (considered to be Japanese and Korean). These genotypes along with other short tandem repeats may help in studying the historical spread of disease and the strains of M. leprae disseminated by various human races that migrated to India from other places of Asia and European countries during our history.
Assuntos
Proteínas de Bactérias/genética , DNA Bacteriano/genética , Hanseníase/microbiologia , Mycobacterium leprae/genética , Fator sigma/genética , Análise do Polimorfismo de Comprimento de Fragmentos Amplificados , Animais , Emigração e Imigração , Genes Bacterianos , Genótipo , Humanos , Índia/epidemiologia , Hanseníase/epidemiologia , Mycobacterium leprae/isolamento & purificação , Dinâmica Populacional , Análise de Sequência de DNA , Pele , Sequências de Repetição em TandemRESUMO
Rifamycins are primarily produced by Gram-positive bacterium Amycolatopsis mediterranei, which belongs to the order Actinomycetales. These antibiotics, apart from their application against pathogens of tuberculosis and leprosy, have also been found to be effective against several other pathogens including Mycobacterium avium and Pneumococcus. Because of the importance of rifamycin, the producer strain A. mediterranei has been genetically manipulated since 1957 in order to develop a strain that can either produce larger amounts of rifamycin or derivatives of rifamycin. In this article, the importance of the producer strain, traditional methods (mutations and recombination) of strain improvement, their limitations, and the development of a cloning vector and transformation methods that have made recombinant DNA techniques accessible for genetic manipulations of A mediterranei are discussed.
Assuntos
Actinobacteria/genética , Actinobacteria/metabolismo , Engenharia Genética/métodos , Rifamicinas/biossíntese , Clonagem Molecular/métodos , Mutação , Recombinação Genética , Rifamicinas/químicaRESUMO
Rifamycin is a clinically useful macrolide antibiotic produced by the gram positive bacterium Amycolatopsis mediterranei. This antibiotic is primarily used against Mycobacterium tuberculosis and Mycobacterium leprae, causative agents of tuberculosis and leprosy, respectively. In these bacteria, rifamycin treatment specifically inhibits the initiation of RNA synthesis by binding to beta-subunit of RNA polymerase. Apart from its activity against the bacteria, rifamycin has also been reported to inhibit reverse transcriptase (RT) of certain RNA viruses. Recently, rifamycin derivatives have been discovered that are effective against Mycobacterium avium, which is associated with the AIDS complex. Consequently, the importance of and demand for rifamycin has increased tremendously, the world over. In this article, recent trends in rifamycin research and accessibility of recombinant DNA techniques to increase rifamycin production are reviewed.
Assuntos
Rifamicinas/uso terapêutico , Infecções Oportunistas Relacionadas com a AIDS/tratamento farmacológico , RNA Polimerases Dirigidas por DNA/antagonistas & inibidores , Resistência Microbiana a Medicamentos , Humanos , Hanseníase/tratamento farmacológico , Estrutura Molecular , Mycobacterium avium/efeitos dos fármacos , Mycobacterium leprae/efeitos dos fármacos , Mycobacterium tuberculosis/efeitos dos fármacos , Inibidores da Transcriptase Reversa , Rifamicinas/biossíntese , Rifamicinas/farmacologia , Tuberculose/tratamento farmacológicoRESUMO
Dapsone (DDS) is a drug of choice in the treatment of leprosy. The DDS and MADDS levels and different pharmacokinetic parameters after a single dose of dapsone and at steady state in leprotic patients have been studied. At steady state, all the patients showed plasma DDS and MADDS levels above 0.5 micrograms/ml throughout the 24-h duration. There was no significant difference in the elimination half-lives of DDS and MADDS after a single dose as compared to at steady state, but AUC0-alpha for both DDS and MADDS were significantly increased at steady state. From these results, it could be concluded that 100 mg daily dose is sufficient to maintain plasma therapeutic concentration in leprotic patients in Indian population.
Assuntos
Dapsona/análogos & derivados , Dapsona/sangue , Hanseníase Virchowiana/metabolismo , Adulto , Cromatografia Líquida de Alta Pressão , Dapsona/administração & dosagem , Dapsona/farmacocinética , Humanos , Hanseníase Virchowiana/tratamento farmacológico , Pessoa de Meia-IdadeRESUMO
Pharmacokinetics of aspirin and chloramphenicol was studied in 16 normal and 16 patients suffering from leprosy. A significant increase (p less than 0.05) in the elimination half-life of chloramphenicol was observed before and after dapsone treatment in leprotic patients as compared with the normal volunteers, while no significant difference was observed in any of the pharmacokinetic parameters with aspirin.