ATENÇÃO FARMACÊUTICA NO TRATAMENTO DE TUBERCULOSE

A Tuberculose (TB) Peste branca ou como é popularmente conhecida, a tuberculose surgiu no continente africano há pelo menos 70.000 anos, acompanhou humanos na evolução e processo de expansão pelo planeta, mesmo hoje em dia considerada uma ameaça para à saúde. A TB é uma doença infecciosa crônica granulomatosa causada por bactérias do grupo das microbactérias. É importante ressaltar que existem microbactérias que podem causar tuberculose e outras que não podem. As principais causadoras são, da mais importante para a menos: tubercle bacillus, Mycobacterium bovis e Mycobacterium africanum. É considerada a doença mais infecciosa e mortal do mundo, responsável por mais de 04 mil mortes diárias no mundo todo, de acordo com a Organização Mundial da Saúde (OMS). Embora afete outros órgãos e / ou sistemas, é uma doença infecciosa e contagiosa que atinge principalmente os pulmões. As formas extrapulmonares que afetam outros órgãos além dos pulmões são mais comuns entre as pessoas com HIV, especialmente aquelas com sistema imunológico enfraquecido. No Brasil, a doença é um grave problema de saúde pública com profundas raízes sociais. A epidemia de HIV e a existência de bacilos resistentes a medicamentos complicaram a situação. Todos os anos, são notificados cerca de 70.000 novos casos e cerca de 4.500 mortes por tuberculose.

About filterable forms of tubercle bacillus

By filtering tuberculous sputum through a Chamberlend'a candle

On changes in the biochemical properties of tubercle bacillus due to its dissociation

On the question of the variability of microbes, since 1888, an enormous amount of material has been accumulated. Hadley (1927), in his monograph, brilliantly summarized all the facts, observations and opinions and subordinated them to the main hypothesis, which is an answer to the question about the essence of the very process of variability. Namely: according to Hadley, each microbial species undergoes a certain cycle of development during its life (dissociation); variability is the external expression of this dissociation.

A Preliminary Study on the Synergistic Effect of Nano Ag and Anti-Tuberculosis Drugs on Drug-Resistant Mycobacterium tuberculosis

To determine the bactericidal effect of nano silver and anti-tuberculosis drugs on drug-resistant Mycobacterium tuberculosis. Solid-state drug sensitivity tests with streptomycin (SM), isoniazid (INH), RIF, EMB, kanamycin (km), and ofloxacin (ofx) were carried out on H37Rv and different clinical isolates. Briefly, the effects of SM, INH, RIF, EMB (1.0 μg/mL, 0.1 μg/mL, 1.0 μg/mL, 5.0 μg/mL), and anti-tuberculosis drugs, and their combined effect with 0.15 μg/mL and 0.30 μg/mL nano silver on drug-resistant tuberculosis bacteria were evaluated by liquid drug sensitivity test. At the low concentration (0.15 μg/mL), nano silver could not effectively kill the tuberculosis strains; however, at concentrations ≥0.30 μg/mL, it could effectively kill H37Rv and the clinical isolates of the sensitive, single-resistant, multi-resistant, multi-resistant, and extensively resistant strains. Combining 0.15 μg/mL nano silver with the four first-line anti-tuberculosis drugs could not effectively kill the tuberculosis strains; however, combining 0.30 μg/mL nano silver and the anti-tuberculosis drugs could effectively kill the drug-resistant tuberculosis strains. Nano silver exhibits a concentrationdependent killing effect on tubercle bacillus. Further, a nano silver concentration higher than 0.30 μg/mL could kill sensitive and resistant tubercle bacillus.

Lsr2 is a nucleoid-associated protein that exerts pleiotropic effects on mycobacterial cellular processes

Lsr2 is involved in maintaining chromosome structure in asymmetrically dividing mycobacteria and is essential in the tubercle bacillus (M. tuberculosis) during infection. Here, we report that a lack of Lsr2 profoundly impacts the mycobacterial cell morphology and the properties of the cell envelope resulting in the formation of smooth, short and antibiotics sensitive cells. Lsr2 forms large and dynamic nucleoprotein complexes in vivo and deletion of lsr2 gene exerts a profound effect on the replication time and replisome dynamics. We suggest that the Lsr2 nucleoprotein complexes may contribute to maintaining the proper organization of the newly synthesized DNA. Moreover, we demonstrate that the N-terminal oligomerization domain of Lsr2 is indispensable for the formation of nucleoprotein complexes in vivo. Collectively, our results indicate that Lsr2 exerts a pleiotropic effect on cellular processes and appears to be an attractive target for the development of a novel antitubercular drugs.

The endogenous galactofuranosidase GlfH1 hydrolyzes mycobacterial arabinogalactan

Despite impressive progress made over the past 20 years in our understanding of mycolylarabinogalactan-peptidoglycan (mAGP) biogenesis, the mechanisms by which the tubercle bacillus Mycobacterium tuberculosis adapts its cell wall structure and composition to various environmental conditions, especially during infection, remain poorly understood. Being the central portion of the mAGP complex, arabinogalactan (AG) is believed to be the constituent of the mycobacterial cell envelope that undergoes the least structural changes, but no reports exist supporting this assumption. Herein, using recombinantly expressed mycobacterial protein, bioinformatics analyses, and kinetic and biochemical assays, we demonstrate that the AG can be remodeled by a mycobacterial endogenous enzyme. In particular, we found that the mycobacterial GlfH1 (Rv3096) protein exhibits exo-β-d-galactofuranose hydrolase activity and is capable of hydrolyzing the galactan chain of AG by recurrent cleavage of the terminal β-(1,5) and β-(1,6)-Galf linkages. The characterization of this galactosidase represents a first step toward understanding the remodeling of mycobacterial AG.

Ensemble deep learning for tuberculosis detection

Tuberculosis (TB) is one of the deadliest infectious disease in the world. TB is caused by a type of tubercle bacillus called Mycobacterium Tuberculosis. Early detection of TB is pivotal to decrease the morbidity and mortality. TB is diagnosed by using the chest x-ray and a sputum test. Challenges for radiologists are to avoid confused and misdiagnose TB and lung cancer because they mimic each other. Semi-automated TB detection using machine learning found in the literature requires identification of objects of interest. The similarity of tissues, veins and small nodules presenting the image at the initial stage may hamper the detection. In this paper, an approach to detect TB, that does not require segmentation of objects of interest, based on ensemble deep learning, is presented. Evaluation on publicly available datasets show that the proposed approach produced a model that recorded the best accuracy, sensitivity and specificity of 91.0%, 89.6% and 90.7% respectively.

A clinical study of association of genital tuberculosis with infertility in a tertiary centre of Jharkhand, India

Background: The worldwide incidence of GTB is approximately 5- 10% in infertile women. It varies from as low as 0.69% in some developed countries to as high as 19% in India. It is diagnosed by culture of the tubercle bacillus from tissue sampled from the genital tract is the yardstick for diagnosis and remains the gold standard.Methods: A prospective study was carried out between January 2012 and January 2015 on 100 women presenting with infertility.Results: A total (27%) women were diagnosed as genital tuberculosis by combination of hystero laparoscopic findings, histopathological and endometrial DNA-PCR technique confirmation. Of these (40.62%) had secondary infertility and remaining (59.38%) had primary infertility. (15.62%) were previously diagnosed with pulmonary or extra pulmonary tuberculosis and had completed a full course of Anti-tubercular treatment as per WHO CAT 1 regime.Conclusions: Therefore, in countries where TB is endemic, early and aggressive strategies should be pursued to diagnose and treat TB.