THE ROLE OF NATURAL ANTIOXIDANTS AS POTENTIAL THERAPEUTIC AGENT IN NEPHROLITHIASIS

Renal injury and inflammation caused by ROS play a major role in stone formation. Under the hyperoxaluric condition, crystal deposition results in angiotensin II (Ang II) activation. NADPH Oxidase is stimulated by activated Ang II, leading to ROS production, which can damage renal cells. Oxidative stress also results in mitochondrial dysfunction and release of pro-apoptotic factors from depolarized mitochondria that result in apoptosis that leads to renal injury. Crystal retention in the kidney requires tubular epithelial injury accompanied by luminal expression of HA, OPN, and CD44. The expression of these molecules turns a non–crystal-binding epithelium into a crystal-binding one, thereby setting the stage for crystal retention. Recently many antioxidants have been studied that prevent hyperoxaluria mediated nephrolithiasis. Antioxidant treatment significantly reduces CaOx crystal deposition in kidneys. Naturally occurring antioxidants such as Vitamin E, Apocynin, Phycocyanin, Fucoidin, Gallotannins, Rottlerin, Lupeol, Curcumin, etc. have shown significant effect in combating renal injury which is an early event in nephrolithiasis. These findings point towards a great potential for the therapeutic application of antioxidants and free radical scavengers to reduce stone occurrence particularly under hyperoxaluric conditions. This review article attempts to compile various naturally occurring antioxidants used in treatment of nephrolithiasis. Keywords: Calcium oxalate, Oxidative stress, Hyperoxaluria, Reactive oxygen species, antioxidant

High pressure investigations on hydrous Magnesium Silicate-Phase A using first principles calculations, H---H repulsion and O-H bond compression

We have carried out first principles structural relaxation calculations on the hydrous magnesium silicate Phase A (Mg7Si2O8(OH)6) under high pressures. Our results show that phase A does not undergo any phase transition upto ~ 45 GPa. We find that nonbonded H---H distance reaches a limiting value of 1.85 Å at about 45 GPa. The H---H repulsive strain releasing mechanism in Phase A is found to be dramatically different from the hydrogen bond bending one that was proposed by Hofmeister et al1 for Phase B. It is based on the reduction of one of the O-H bond distances with compression

Computed tomography guided fine needle aspiration cytology of mass lesions of lung: our experience in a tertiary care hospital

Background: The present study was undertaken to evaluate the diagnostic usefulness of image guided fine needle aspiration cytology (FNAC) in various lung lesions-both neoplastic and non- neoplastic.Method: This retrospective study (Jan 2016-Dec 2018) included 34 cases of lung lesions with strong probable radiological diagnosis of lung neoplasm. Computed tomography (CT)-guided FNAC was performed and cytological smears were stained with May-Grunwald-Gimesa (MGG) stain and conventional Papanicolaou (Pap) stain.Result: A total of 34 cases of lung masses in our study, included 21 males (61.7%) and 13 females (38.2%). The age interval varied from 15 to 85 years; majority presenting in 6th and 7th decade of age. Smears were broadly categorized into unsatisfactory (n=2;5.88%), benign (n=3;8.82%), suspicious of malignancy (n=2;5.88%) and malignant lesions (n=27;79.41%). Benign category included 2 cases of tuberculosis and 1 case of abscess. Malignant category included the cases, diagnosed as squamous cell carcinoma(n=8); poorly differentiated carcinoma (n=6); small cell carcinoma (n=3); adenoma carcinoma (n=2); primitive neuroectodermal tumor (n=2); non-Hodgkins lymphoma (n=2) and plasmacytoma (n=1). Malignant category also included one case each of Metastatic Adenocarcinoma, adenoid cystic carcinoma, renal cell carcinoma with known primary site of Tumours.Conclusions: CT-guided FNAC is a less expensive, simple, fast, relatively safe and accurate procedure in the diagnosis of difficult lung lesions; the major limitation being the adequacy of the aspirate.

High pressure investigations on Hydrous Magnesium Silicate-Phase A using first principles calculations, H---H repulsion and O-H bond compression

We have carried out first principles structural relaxation calculations on the hydrous magnesium silicate Phase A (Mg 7 Si 2 O 8 (OH) 6 ) under high pressures. Our results show that phase A does not undergo any phase transition upto ~ 45 GPa. We find that nonbonded H---H distance reaches a limiting value of 1.85 Å at about 45 GPa. The H---H repulsive strain releasing mechanism in Phase A is found to be dramatically different from the hydrogen bond bending one that was proposed by Hofmeister et al 1 for Phase B. It is based on the reduction of one of the O-H bond distances with compression

Differential responsiveness of MET inhibition in non-small-cell lung cancer with altered CBL.

Casitas B-lineage lymphoma (CBL) is an E3 ubiquitin ligase and a molecule of adaptor that we have shown is important for non-small-cell lung cancer (NSCLC). We investigated if MET is a target of CBL and if enhanced in CBL-altered NSCLC. We showed that CBL wildtype cells have lower MET expression than CBL mutant cells. Ubiquitination of MET was also decreased in CBL mutant cells compared to wildtype cells. Mutant cells were also more sensitive to MET inhibitor SU11274 than wild-type cells. sh-RNA-mediated knockdown of CBL enhanced cell motility and colony formation in NSCLC cells, and these activities were inhibited by SU11274. Assessment of the phospho-kinome showed decreased phosphorylation of pathways involving MET, paxillin, EPHA2, and VEGFR. When CBL was knocked down in the mutant cell line H1975 (erlotinib-resistant), it became sensitive to MET inhibition. Our findings suggest that CBL status is a potential positive indicator for MET-targeted therapeutics in NSCLC

Low temperature and high pressure Raman and x-ray studies of pyrochlore Tb2_2Ti2_2O7_7 : phonon anomalies and possible phase transition

We have carried out temperature and pressure-dependent Raman and x-ray measurements on single crystals of Tb$_2$Ti$_2$O$_7$. We attribute the observed anomalous temperature dependence of phonons to phonon-phonon anharmonic interactions. The quasiharmonic and anharmonic contributions to the temperature-dependent changes in phonon frequencies are estimated quantitatively using mode Gr\"{u}neisen parameters derived from pressure-dependent Raman experiments and bulk modulus from high pressure x-ray measurements. Further, our Raman and x-ray data suggest a subtle structural deformation of the pyrochlore lattice at $\sim$ 9 GPa. We discuss possible implications of our results on the spin-liquid behaviour of Tb$_2$Ti$_2$O$_7$.Comment: 10 figures, 26 pages. Appeared in Physical Review B, vol-79, pp-134112 (2009

High pressure phase transitions in organic solids. I: α → β transition in resorcinol

An experimental program has been started to study polymorphic phase transitions under pressure in organic solids using the Be gasketing technique developed by us. This allows us to obtain x-ray diffraction patterns of low symmetry organic solids with high resolution, employing CuK α radiation. The first organic solid studied is α-resorcinol. At 0.5 GPa, it transforms to its high temperature and denser modification, β-resorcinol. The transformation mechanism is discussed with the help of molecular packing calculations

Prognostic signifi cance of diff erentiating necrosis from fl uid collection on endoscopic ultrasound in patients with presumed isolated extrapancreatic necrosis

Abstract Background Extrapancreatic necrosis is diagnosed on computed tomography (CT) as extrapancreatic changes that are more than fat stranding; both fl uid collections and necrosis would have a similar appearance. Th e aim of this study was to determine the prognostic signifi cance of diff erentiating peripancreatic necrosis from fl uid collection on endoscopic ultrasound (EUS) in patients with presumed isolated extrapancreatic necrosis