Isolation,structural determination,synthesis and quantitative determination of impurities in Intron-A,leached from a silicone tubing

Investigation of unexpected levels of impurities in Intron product has revealed the presence of low levels of impurities leached from the silicone tubing (Rehau RAU-SIK) on the Bosch filling line. In order to investigate the effect of these compounds (1a, 1b and 2) on humans, they were isolated identified and synthesized. They were extracted from the tubing by stirring in Intron placebo at room temperature for 72 h and were enriched on a reverse phase CHP-20P column, eluting with gradient aqueous ACN and were separated by HPLC. Structural elucidation of 1a, 1b and 2 by MS and NMR studies demonstrated them to be halogenated biphenyl carboxylic acids. The structures were confirmed by independent synthesis. Levels of extractable impurities in first filled vials of actual production are estimated to be in the range of 0.01–0.55 μg/vial for each leached impurity. Potential toxicity of these extractables does not represent a risk for patients under the conditions of clinical use.     

Protein content of human apatite and brushite kidney stones: significant correlation with morphologic measures

Apatite and brushite kidney stones share calcium and phosphate as their main inorganic components. We tested the hypothesis that these stone types differ in the amount of proteins present in the stones. Intact stones were intensively analyzed by microcomputed tomography (micro CT) for both morphology (including the volume of voids, i.e., space devoid of X-ray dense material) and mineral type. To extract all proteins present in kidney stones in soluble form we developed a three-step extraction procedure using the ground stone powder. Apatite stones had significantly higher levels of total protein content and void volume compared to brushite stones. The void volume was highly correlated with the total protein contents in all stones (r ² = 0.61, P < 0.0001), and brushite stones contained significantly fewer void regions and proteins than did apatite stones (3.2 ± 4.5% voids for brushite vs. 10.8 ± 11.2% for apatite, P < 0.005; 4.1 ± 1.6% protein for brushite vs. 6.0 ± 2.4% for apatite, P < 0.03). Morphological observations other than void volume did not correlate with protein content of stones, and neither did the presence or absence of minor mineral components. Our results show that protein content of brushite and apatite stones is higher than that was previously thought, and also suggest that micro CT-visible void regions are related to the presence of protein.     

Persistence of Napropamide in/on Tea under North-East Indian Climatic Condition

Napropamide is an amide group of herbicide, used as pre-emergence herbicide controlling in broad leaved weeds of tea, ground nut, citrus, etc. Napropamide 45 SC (Devrinol) was applied on tea bushes twice @ 1.125 and 2.250 g a.i./ha along with untreated control. After following the standard extraction process, the residue of napropamide in made tea and soil cropped with tea was analyzed by HPLC. Napropamide was rapidly dissipated in soil following the first-order kinetics with half-lives in the range of 12.54–27.87 days. The residue in made tea found to be below detectable limit on 7th day samples.     

A New Approach of Canopy Temperature based Irrigation Scheduling of Wheat in Humid Subtropical Climate of India

Proceedings of the National Academy of Sciences, India Section B: Biological Sciences - The aim of the study is to develop a new canopy temperature based index named plant stress index (PSI) as an...     

Inhibition of β-Catenin signaling suppresses pancreatic tumor growth by disrupting nuclear β-Catenin/TCF-1 complex: Critical role of STAT-3

Aberrant activation of β-catenin/TCF signaling is related to the invasiveness of pancreatic cancer. In the present study, we evaluated the effect of capsaicin on β-catenin/TCF signaling. In a concentration and time-dependent study, we observed that capsaicin treatment inhibits the activation of dishevelled (Dsh) protein DvI-1 in L3.6PL, PanC-1 and MiaPaCa-2 pancreatic cancer cells. Capsaicin treatment induced GSK-3β by inhibiting its phosphorylation and further activated APC and Axin multicomplex, leading to the proteasomal degradation of β-catenin. Expression of TCF-1 and β-catenin-responsive proteins, c-Myc and cyclin D1 also decreased in response to capsaicin treatment. Pre-treatment of cells with MG-132 blocked capsaicin-mediated proteasomal degradation of β-catenin. To establish the involvement of β-catenin in capsaicin-induced apoptosis, cells were treated with LiCl or SB415286, inhibitors of GSK-3β. Our results reveal that capsaicin treatment suppressed LiCl or SB415286-mediated activation of β-catenin signaling. Our results further showed that capsaicin blocked nuclear translocation of β-catenin, TCF-1 and p-STAT-3 (Tyr705). The immunoprecipitation results indicated that capsaicin treatment reduced the interaction of β-catenin and TCF-1 in the nucleus. Moreover, capsaicin treatment significantly decreased the phosphorylation of STAT-3 at Tyr705. Interestingly, STAT-3 over expression or STAT-3 activation by IL-6, significantly increased the levels of β-catenin and attenuated the effects of capsaicin in inhibiting β-catenin signaling. Finally, capsaicin mediated inhibition of orthotopic tumor growth was associated with inhibition of β-catenin/TCF-1 signaling. Taken together, our results suggest that capsaicin-induced apoptosis in pancreatic cancer cells was associated with inhibition of β-catenin signaling due to the dissociation of β-catenin/TCF-1 complex and the process was orchestrated by STAT-3.