Bronchoscopic evaluation and final diagnosis in patients with chronic non productive cough with normal Chest X ray

When a proper detailed history, clinical examination, chest X ray and sputum analysis does not yield a definite diagnosis for the cause of chronic cough, bronchoscopy is indicated. We did a descriptive study among 39 patients who underwent bronchoscopic evaluation for chronic cough (more than 4 weeks) with normal chest X ray and without a prior definitive diagnosis. 16 out of 39 patients were diagnosed to have tuberculosis on analysis of the bronchial washings. 6 patients (66.67%) with left upper lobe mucosal inflammation were AFB smear positive. 5 patients ( 31.25 %) with normal bronchoscopy were AFB smear positive.4 out of 5 patients (80 %) with bilateral upper lobe mucosal inflammation were AFB smear positive. Pulmonary tuberculosis can present with chronic non productive cough and normal chest X ray. Bronchoscopy is helpful in establishing the diagnosis. When bronchoscopy shows bilateral or unilateral upper lobe bronchial mucosal inflammation, possibility of tuberculosis is high. Bronchoscopy can be normal in some patients with pulmonary tuberculosis with normal chest x ray and chronic non productive cough. The key message is that early pulmonary tuberculosis can present with chronic non productive cough and normal chest X ray without any other symptoms suggestive of tuberculosis. Bronchoscopy is helpful in establishing the diagnosi

In silico identification of potential inhibitors for human aurora kinase b

Cell cycle progression through mitosis and meiosis involves regulation by serine/threonine kinases from the aurora family. Aurora kinase b (Aurkb) is mainly involved in the proper segregation of chromosomes during mitosis as well as meiosis. However, over expression of Aurkb leads to the unequal distribution of genetic information creating aneuploid cells, a hallmark of cancer. Thus, Aurkb can be used as an effective molecular target for computer-aided drug discovery against cancer. Existing Aurkb inhibitors are less efficient, hence an in silico work was carried out to identify novel potent inhibitors. Three published inhibitors azd1152, zm447439 and N-(4-{[6-methoxy-7-(3-morpholin-4-ylpropoxy) quinazolin- 4-yl] amino} phenyl) benzamide were subjected to high throughput virtual screening of over 1 million entries from a ligand info meta database, to generate a 1161 compound library. The crystal structure was optimized and energy was minimized applying an OPLS force field in Maestro v9.0. Molecular docking using Glide was performed to predict the binding orientation of the prepared ligand molecule into a grid of 20*20*20 Å created around the centroid of the optimized human Aurkb protein. Nine lead molecules with good binding affinity with human Aurkb were identified. In silico pharmacokinetics study for these nine lead molecules has shown no ADME violation. Analysis of lead ‘1’- human Aurkb docking complex has revealed a XP Gscore of -10.20 kcal/mol with a highly stabilized hydrogen bond network with Asp218 and Ala157 and good Van der wall interactions. The docking complex coincides well with the native co- crystallized human Aurkb and inhibitor zm447439 complex. Thus, lead 1 would be highly useful for developing potential drug molecules for the treatment of cancer

Bidirectional motion of filaments: Role of motor proteins and passive cross linkers

In eukaryotic cells, motor proteins (MP) bind to cytoskeletal filaments and move along them in a directed manner generating active stresses. During cell division a spindle structure of overlapping antiparallel microtubules (MT) form whose stability and dynamics under the influence of MPs has been studied extensively. Although passive cross linkers (PCL) were known to provide structural stability to filamentous network, consequences of the interplay between ATP dependent active forces of MPs and passive entropic forces of PCLs on MT overlap remains largely unexplored. Here, we formulate and characterize a model to study this, using linear stability analysis and numerical integration. In presence of PCLs, we find dynamic phase transitions with changing activity exhibiting regimes of stable partial overlap with or without oscillations, instability towards complete overlap, and stable limit cycle oscillations that emerge via a supercritical Hopf bifurcation characterized by an oscillation frequency determined by the MP and PCL parameters. We show that the overlap dynamics and stability depend crucially on whether both the MTs of overlapping pair are movable or one is immobilized, having potential implications for in vivo and in vitro studies.Comment: 13 pages, 9 figure