A tuberculosis prevalence survey based on symptoms questioning and sputum examination

A sample survey was undertaken in Raichur district of Karnataka State to estimate the prevalence of bacteriologically positive pulmonary tuberculosis among symptomatics aged 15 years and above. A population of 72,448 persons was registered in a representative sample of 57 villages and 21 enumeration blocks. Of the 42,580 persons aged 15 years and above eligible for symptoms questioning, 40,657 (95.5%) were examined and 3,846 (9.5%) were found to be symptomatics and eligible for sputum examination. Sputum was collected from 3,685 (95.8%) of the 3,846 symptomatics, and subjected to bacteriological examination i.e., smear, culture and drug susceptibility. Certain important findings were as follows: (i) the number of symptomatics increased with increase in age, more often among males (11.9%) than among females (7.1%), (ii) the prevalence of tuberculosis, as assessed by smear and/or culture was 10.9 per 1,000 in population aged 15 years and above, (iii) the prevalence increased with age and was 3 times higher among males as compared to females, (iv) cough was found to be the predominant symptom among the symptomatics (87%) as well as among the cases detected (92%), (v) the prevalence rate based on smear examination of the sputum specimens, using the two microscopy methods (Ziehl-Neelsen and Fluorescence) was 7.6 per 1,000, (vi) culture examination of these specimens yielded 3.3 per 1,100 additional cases, (vii) both the microscopy methods were equally efficient in detecting smear positives, (vii) of the 355 culture positive cases, 17.7% were resistant to Streptomycin, 29.6% to Isoniazid and 7.6% to Rifampicin either alone or in combination with other drugs

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Targeting MYC Dependence by Metabolic Inhibitors in Cancer

Abstract: MYC is a critical growth regulatory gene that is commonly overexpressed in a wide range of cancers. Therapeutic targeting of MYC transcriptional activity has long been a goal, but it has been difficult to achieve with drugs that directly block its DNA-binding ability. Additional approaches that exploit oncogene addiction are promising strategies against MYC-driven cancers. Also, drugs that target metabolic regulatory pathways and enzymes have potential for indirectly reducing MYC levels. Glucose metabolism and oxidative phosphorylation, which can be targeted by multiple agents, promote cell growth and MYC expression. Likewise, modulation of the signaling pathways and protein synthesis regulated by adenosine monophosphate-activated protein kinase (AMPK) and mechanistic target of rapamycin (mTOR) can also be an effective route for suppressing MYC translation. Furthermore, recent data suggest that metabolism of nucleotides, fatty acids and glutamine are exploited to alter MYC levels. Combination therapies offer potential new approaches to overcome metabolic plasticity caused by single agents. Although potential toxicities must be carefully controlled, new inhibitors currently being tested in clinical trials offer significant promise. Therefore, as both a downstream target of metabolism and an upstream regulator, MYC is a prominent central regulator of cancer metabolism. Exploiting metabolic vulnerabilities of MYC-driven cancers is an emerging research area with translational potential

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Synthesis and cytotoxic evaluation of novel 2-(4-(2, 2, 2-trifluoroethoxy)-3-methylpyridin-2-ylthio)-1H-benzo [d] imidazole derivatives

The present work deals with the anticancer effect of benzimidazole derivatives associated with the pyridine framework. By varying the functional group at N-terminal of the benzimidazole by different L-amino acids, several 2-(4-(2,2,2-trifluoroethoxy)-3-methylpyridin-2-ylthio)-1Hbenzo[d]imidazole derivatives 9(a–j) were synthesized. Their chemical structures were confirmed by 1H NMR, IR and mass spectroscopic techniques. The synthesized compounds were examined for their antiproliferative effects against human leukemia cell lines, K562 and CEM. The preliminary results showed most of the derivatives had moderate antitumor activity. Compound 9j containing cysteine residue exhibited good inhibition compared to other amino acid resides. In addition DNA fragmentation results suggest that 9j is more cytotoxic and able to induce apoptosis

Synthesis and identification of a new class of antileukemic agents containing 2-(arylcarboxamide)-(S)-6-amino-4,5,6,7-tetrahydrobenzodthiazole

Recently we have reported the effect of (S)-6-aryl urea/thiourea substituted-2-amino-4,5,6,7-tetrahydrobenzodthiazole derivatives as potent anti-leukemic agents. To elucidate further the Structure Activity Relationship (SAR) studies on the anti-leukemic activity of (S)-2,6-diamino-4,5,6,7-tetrahydrobenzodthiazole moiety, a series of 2-arlycarboxamide substituted–(S)-6-amino-4,5,6,7-tetrahydrobenzodthiazole were designed, synthesized and evaluated for their anti-leukemic activity by trypan blue exclusion, 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT), lactate dehydrogenase (LDH) assays and cell cycle analysis. Results suggest that the position, number and bulkiness of the substituent on the phenyl ring of aryl carboxamide moiety at 2nd position of 6-amino-4,5,6,7-tetrhydrobenzodthiazole play a key role in inhibiting the proliferation of leukemia cells. Compounds with ortho substitution showed poor activity and with meta and para substitution showed good activity