Navegando por Assunto "Isoniazida"

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Acesso aberto (Open Access)
Diminuição da sensibilidade ao contraste espacial de luminância em sujeitos com história de uso de terapia medicamentosa anti-tuberculose
(Universidade Federal do Pará, 2012) GOMES, Janildes Maria Silva; SOUZA, Givago da Silva; http://lattes.cnpq.br/5705421011644718
The drugs isoniazid and ethambutol, usually administed for tubercolosis treatment, are well known to cause damage in the visual system of the patients that use them. As vision is an important sense for the quality of life and the luminance contrast is considered a good biomarker for visual evaluation, the present study aimed to compare the contrast sensitivity estimated from subjects that used anti-tuberculosis drug therapy and age-matched healthy subjects. The study was performed in Imperatriz city, Balsas city, Davinópolis city and Governador Edson Lobão city, in Maranhão state, Brazil from 2009 to 2012. The current study had a transversal, analytic, and case control profile. Three group of subjects participated from the present study: Control group (n=40), group of subjects treated with isoniazid (n = 19), and group of subjects that used isoniazid associated with ethambutol (n=18). It was used a CRT monitor, 21”, 6 x 5 degrees of visual angle to investigate the contrast sensitivity function. The comparison of the contrast sensitivities at different spatial frequencies among the three studied groups showed statistical differences (Two-way ANOVA, Tukey test, p < 0,05). Control group had higher contrast sensitivity at 10 and 15 cpd than the group that used only isoniazid as drug therapy for tuberculosis treatment and control group had higher contrast sensitivity at 4, 6, 10, 15 and 20 cpd than the group the received isoniazid and ethambutol together. There were no differences between the groups that received anti-tuberculosis therapy.
Acesso aberto (Open Access)
Estudo teórico das interações entre inibidores da inha, enoil acp redutase do mycobacterium tuberculosis
(Universidade Federal do Pará, 2017-09-29) BAHIA, Jeann Ricardo da Costa; CARNEIRO, Agnaldo da Silva; http://lattes.cnpq.br/8915348778787525
Isoniazid is the oldest, cheapest and most effective synthetic prodrug of the first line of treatment for Tuberculosis. It should be activated by the Mycobacterium tuberculosis catalase-peroxidase, KatG, which produces an isonicotinoyl-NADH adduct, INNADH, which targets the M. tuberculosis Enoyl-ACP reductase protein, InhA, in order to disrupt the synthesis chain of mycolic acids. Resistance to isoniazid alone or in combination with other drugs is one of the most common forms of resistant tuberculosis and poses a threat to the control of this disease. In this context, triclosan (TCL) appears as an alternative inhibitor of the synthesis of mycolic acids, since it is also specific to InhA. This study aims to evaluate the interactions of inhibitors of InhA through Molecular Dynamics Simulation (DM) and propose possible new inhibitors for this enzyme. The system used in this work was captured from the database PDB, code 4TRO. Eight ligands, NADH, INNADH, and the TCL, P31, P41, P52, P61, P72 and P80 derivatives were evaluated. In the lower region of the active site of InhA were more frequent π charge stacks made by PHE41 and PHE97 with the ligands NADH, INADH, P80, P31, P72, however P41 made a hydrogen bond (LH) with PHE41. In the central region of the active site, residues such as A GLY96, SER20 and ILE21 did LH with NADH, INNADH, P31, P41 and P80. In relation to the upper region of the InhA site. The PHE149 performed EC-π with the INNADH and P41. Already in P31 was an LH with this residue and in P80 the energies are favorable for interaction. The free energies of each system presented in descending order are INNADH (-72,038 kcal / mol), P80 (-45,841 kcal / mol), NADH (- 41,463 kcal / mol), P41 (-40,178 kcal / mol), P31 (-30.614 kcal / mol), p52 (-19.475 kcal / mol) and P61 (-12.297 kcal / mol). These results highlight P80 and P41 as promising candidates for M. tuberculosis mycolic acid synthesis inhibitors, since being an energy profile is competitive with the values shown by NADH.