METHOD DEVELOPMENT AND VALIDATION OF EPROSARTAN MESYLATE AND ITS IMPURITIES USING REVERSE PHASE HIGH-PERFORMANCE LIQUID CHROMATOGRAPHY

Objective: Our main objective is to develop an accurate and precise RP-HPLC method for the determination of Eprosartan Mesylate and its impurities. Methods: A Develosil ODS UG-5; (150 × 4.6) mm; 5 µm column was used for the Separation of drugs by a mobile phase consisting of Buffer and Acetonitrile mixture in the gradient proportion. The flow rate maintained was 0.8 ml/min and the wavelength used for detection was 235 nm.Results: The linearity was observed in the range of 0.025-50µg/ml of spiked impurities in Eprosartan Mesylate, impurity 1 and impurity 2 with a correlation coefficient of 0.99927, 0.99910 and 0.99934 respectively. The mean percentage recoveries for LOQ, 50%, 80%, 100%, 150% and 200% accuracy were found to be 101.5±1.51, 107.0±1.7, 104.6±0.4, 102.8±0.36, 101.7±0.26 and 101.3±0.15 respectively for impurities in Eprosartan Mesylate, impurity 1 and impurity 2. Linearity, accuracy, precision and robustness parameters for the suggested method were estimated for validation.Conclusion: The developed method is uncomplicated, accurate, sensitive and precise for the determination of related substances in the Eprosartan Mesylate. The satisfying % recoveries and low % RSD Values confirmed the suitability of the developed method for the usual analysis of Eprosartan mesylate in pharmaceuticals

Diagnostic pathways and direct medical costs incurred by new adult pulmonary tuberculosis patients prior to anti-tuberculosis treatment - Tamil Nadu, India.

BACKGROUND: Tuberculosis (TB) patients face substantial delays prior to treatment initiation, and out of pocket (OOP) expenditures often surpass the economic productivity of the household. We evaluated the pre-diagnostic cost and health seeking behaviour of new adult pulmonary TB patients registered at Primary Health Centres (PHCs) in Vellore district, Tamil Nadu, India. METHODS: This descriptive study, part of a randomised controlled trial conducted in three rural Tuberculosis Units from Dec 2012 to Dec 2015, collected data on number of health facilities, dates of visits prior to the initiation of anti-tuberculosis treatment, and direct OOP medical costs associated with TB diagnosis. Logistic regression analysis examined the factors associated with delays in treatment initiation and OOP expenditures. RESULTS: Of 880 TB patients interviewed, 34.7% presented to public health facilities and 65% patients sought private health facilities as their first point of care. The average monthly individual income was $77.79 (SD 57.14). About 69$39.74. Overall, patients experienced a median of 6 days (3-11 IQR) of time to treatment initiation and 21 days (10-30 IQR) of health systems delay. Age ≤ 40 years (aOR: 1.73; CI: 1.22-2.44), diabetes (aOR: 1.63; CI: 1.08-2.44) and first visit to a private health facility (aOR: 17.2; CI: 11.1-26.4) were associated with higher direct OOP medical costs, while age ≤ 40 years (aOR: 0.64; CI: 0.48-0.85) and first visit to private health facility (aOR: 1.79, CI: 1.34-2.39) were associated with health systems delay. CONCLUSION: The majority of rural TB patients registering at PHCs visited private health facilities first and incurred substantial direct OOP medical costs and delays prior to diagnosis and anti-tuberculosis treatment initiation. This study highlights the need for PHCs to be made as the preferred choice for first point of contact, to combat TB more efficiently.Eunice Kennedy Shriver National Institute of Child Health and Human Developmen

The tribological behaviour of detonation sprayed TiMo(CN) based cermet coatings

The objective of the present study was to evaluate the tribological performance of 200 μm thick TiMo(CN)-28Co and TiMo(CN)-36NiCo coatings obtained using the detonation spray coating system. Towards the above purpose, the detonation spray coating conditions were optimized to obtain the best coating properties (low porosity, high wear resistance) by varying two of the important coating process variables, i.e., oxygen to fuel ratio and gas volume. In both the coatings it was observed that the best tribological performance and also the lowest porosity were obtained at intermediate OF ratios. However, the coatings with the highest hardness did not exhibit the best tribological performance. A comparison of the tribological performance of the optimized TiMo(CN) type coatings with that of optimized WC-Co coatings revealed that the abrasion resistance of TiMo(CN) type coatings is comparable to that of WC-Co coatings. However, the erosion and sliding wear resistance of TiMo(CN) type coatings were considerably lower than that of WC-Co coatings

Interplay between Endoplasmic Reticular Stress and Survivin in Colonic Epithelial Cells

Sustained endoplasmic reticular stress (ERS) is implicated in aggressive metastasis of cancer cells and increased tumor cell proliferation. Cancer cells activate the unfolded protein response (UPR), which aids in cellular survival and adaptation to harsh conditions. Inhibition of apoptosis, in contrast, is a mechanism adopted by cancer cells with the help of the inhibitor of an apoptosis (IAP) class of proteins such as Survivin to evade cell death and gain a proliferative advantage. In this study, we aimed to reveal the interrelation between ERS and Survivin. We initially verified the expression of Survivin in Winnie (a mouse model of chronic ERS) colon tissues by using immunohistochemistry (IHC) and immunofluorescence (IF) in comparison with wild type Blk6 mice. Additionally, we isolated the goblet cells and determined the expression of Survivin by IF and protein validation. Tunicamycin was utilized at a concentration of 10 µg/mL to induce ERS in the LS174T cell line and the gene expression of the ERS markers was measured. This was followed by determination of inflammatory cytokines. Inhibition of ERS was carried out by 4Phenyl Butyric acid (4PBA) at a concentration of 10 mM to assess whether there was a reciprocation effect. The downstream cell death assays including caspase 3/7, Annexin V, and poly(ADP-ribose) polymerase (PARP) cleavage were evaluated in the presence of ERS and absence of ERS, which was followed by a proliferative assay (EdU click) with and without ERS. Correspondingly, we inhibited Survivin by YM155 at a concentration of 100 nM and observed the succeeding ERS markers and inflammatory markers. We also verified the caspase 3/7 assay. Our results demonstrate that ERS inhibition not only significantly reduced the UPR genes (Grp78, ATF6, PERK and XBP1) along with Survivin but also downregulated the inflammatory markers such as IL8, IL4, and IL6, which suggests a positive correlation between ERS and the inhibition of apoptosis. Furthermore, we provided evidence that ERS inhibition promoted apoptosis in LS174T cells and shortened the proliferation rate. Moreover, Survivin inhibition by YM155 led to a comparable effect as that of ERS inhibition, which includes attenuation of ERS genes and inflammatory markers as well as the promotion of programmed cell death via the caspase 3/7 pathway. Together, our results propose the interrelation between ERS and inhibition of apoptosis assigning a molecular and therapeutic target for cancer treatment

A scanning electron microscopic study to observe the changes in the growth morphology of the alpha phased Alumina-13 wt.% titania coatings during plasma spraying

Plasma spraying of Alumina-13 wt.% titania coatings shows preferential stability of a phase, in the as sprayed conditions, to an extent of 15-40%. As reported in the literature, the quantity of this alpha phase can be considered to be closely related to the processing parameters of the air plasma spray process, such as arc current, plasma gas flow rate etc. Normally, a lower value of arc current, results in larger quantity of preferentially stabilized a phase. In this paper, we have attempted to measure the orientation image mapping (OIM) of these alpha phased Alumina-13 wt.% titania coatings with Electron Back Scattered Diffraction. From the OIM, the pole figures for the a phase were established and from appropriate pole figures, such as (0001), (0006), (01T1) and (1011) the growth morphology of the alpha phase could be determined. For larger values of arc current, at which the growth rate is faster and due to the imposed rapid solidification conditions, the hexagonal basal plane of (0001)-H type of the alpha phase tends to align with the (001) type FCC faces of the metastable gamma phase. This alignment can be considered to be similar to a directionally solidified chill cast texture. On the other hand, at slower growth rate and at lower arc current value not only a larger quantity of alpha phase forms, but for accommodation of these larger number of a grains in the thinner section of splats there appears to be a need for a change in the growth morphology. (100)-R type rhombohedral faces, with shorter axial dimensions were found to align in preference to the directional solidified (0001)-H type basal planar arrangement. This type of change in growth morphology can possibly accommodate more a grains for the same thickness of the splat as compared to a basal plane (0001)-H type arrangement. (C) 200