FORMULATION AND OPTIMIZATION OF BUOYANT IN SITU GELLING SYSTEM OF VALSARTAN USING NATURAL POLYMER

Objective: Currently natural polymers have wide spread importance in fabrication of controlled drug delivery systems. Hence in this study ocimum basilicum mucilage, (OBM) a natural polymer used to know its effect as polymer alone and in combination with HPMC K15M and Guargum in oral in situ floating gel of Valsartan using 3 full level factorial design.Methods: FTIR studies conducted to know major drug polymer interactions. OBM, HPMC K15M and Guargum were chosen as three independent variables and examined at 3 levels for in vitro buoyancy (Y1) and drug release at 10 h (Y2) as responses. By using mathematical model approach formulation variables were quantitatively evaluated, and optimized formulation (VFIG) subjected for in vitro buoyancy, density, pH, in vitro drug release, drug content, gelling capacity and drug release kinetics. In addition VFIG studied for In vivo buoyancy and release kinetics.Results: FTIR studies revealed that excipients were compatible with drug. ANOVA results shown that independent variables have significant effect (p<0.05) on both the responses. Observed responses of optimized formulation (3 % OBM, 0.88 % HPMC and 1.25 % Guar gum) were in good agreement with the experimental values. Results of all in vitro evaluations lies within the limits and drug release kinetics followed non-fickian diffusion mechanism. In vivo buoyancy study in rabbit evidenced floatation for>8 h and in vivo pharmacokinetic study exhibited increased bioavailability of optimized formulation.Conclusion: Prepared VFIG with optimized concentrations of OBM, HPMC K15M and Guargum exploiting as a promising dosage form for enhanced gastric delivery

Pyoderma gangrenosum: a presenting sign of myelodysplastic syndrome in undiagnosed Fanconi anemia

A 26-year-old man with a history of congenital bilateral microtia, unilateral renal agenesis, left aural atresia, and right external auditory canal occlusion admitted for right rib cartilage graft harvest and left ear re-construction. Following surgery, an ulceration with violaceous borders and a yellow fibrinous base unresponsive to broad-spectrum antibiotics developed at the harvest site. The wound was expanding and not responsive to systemic broad-spectrum antibiotics. Biopsy revealed a dense dermal infiltrate of neutrophils with negative tissue cultures consistent with pyoderma gangrenosum (PG). He was treated with systemic, intralesional, and topical steroids, as well as doxycycline. Three weeks after the diagnosis of PG, he was found to have persistent anemia and leukopenia. Bone marrow aspiration analysis was consistent with hypocellular myelodysplastic syndrome and genetic testing was consistent with Fanconi anemia. There is a well-known association of PG with hematological disorders. Fanconi anemia is a rare genetic hematologic disorder with congenital defects leading to bone marrow failure and malignancy in long-standing disease. In our patient, we consider his development of PG a paraneoplastic sign associated with the onset of his hypocellular myelodysplastic syndrome

STABILITY-INDICATING REVERSED-PHASE HIGH-PERFORMANCE LIQUID CHROMATOGRAPHY METHOD FOR SIMULTANEOUS ESTIMATION OF METHYLCOBALAMIN, ALPHA-LIPOIC ACID, PYRIDOXINE HCL, AND FOLIC ACID IN BULK AND COMBINED DOSAGE FORM

Objectives: The purpose of the research is to develop a simple, precise, economical, accurate, reproducible, and sensitive method for the estimation of methylcobalamin, alpha-lipoic acid, pyridoxine hydrochloride, and folic acid drug product by reversed-phase high-performance liquid chromatography (RP-HPLC) method.Methods: New analytical method was developed for the estimation of methylcobalamin, alpha-lipoic acid, pyridoxine hydrochloride, and folic acid in drug product by RP-HPLC. The chromatographic separation was achieved on the Inertsil C18, 250 mm × 4.6 mm, 5 μm at ambient temperature. The separation achieved employing a mobile phase consists of buffer (added 5.05 g hexane-1-sulfonic acid is dissolved into 1000 mL of distilled water):acetonitrile in the ratio of 10:90% v/v. The flow rate was 1 mL/min and UV-visible spectrophotometer at 285 nm. The average retention time for methylcobalamin, alpha-lipoic acid, pyridoxine hydrochloride, and folic acid was found to be 3.5, 6.7, 8.5, and 9.3, respectively.Results: The developed method was validated as per ICH guidelines. All validation parameters were within the acceptable ranges. The assay methods were found to be linear from 0 to 2130 μg/mL for methylcobalamin, 0 to 142.5 μg/mL for alpha-lipoic acid, 0–4.54 μg/mL for pyridoxine hydrochloride, and 0–2 μg/mL for folic acid. The correlation coefficient was 0.999 for all drugs, respectively. The mean percentage values for the developed method were found to be within the range of 98–100.6%. The developed method was also found to be robust.Conclusion: It is concluded that developed method was accurate, precise, linear, reproducible, robust, and sensitive

Assessment of Mechanical Property of Ti-5Ta-2Nb and 304L SS Explosive Clad and Correlation with Microstructure

AbstractSpent fuel reprocessing plants of FBRs require advanced structural materials for service in aggressive conditions. Ti-5Ta-2Nb is a candidate structural material for electrolytic dissolver whereas 304L SS is used for rest of the plant. ‘Zero failure’ requirement for the process vessels necessitated the development of defect free explosive clad between Ti-5Ta-2Nb and 304L SS. The paper deals with the investigations carried out on the mechanical properties and microstructure of the explosive clads, and modification in microstructure on subsequent thermal exposure. The structural integrity of the clad as a consequence of these structure-property changes is also discussed in the paper

Pyrenylpyridines: Sky-Blue Emitters for Organic Light-Emitting Diodes

A novel sky-blue-emitting tripyrenylpyridine derivative, 2,4,6-tri(1-pyrenyl)-pyridine (2,4,6-TPP), has been synthesized using a Suzuki coupling reaction and compared with three previously reported isomeric dipyrenylpyridine (DPP) analogues (2,4-di(1 pyrenyl)pyridine (2,4-DPP), 2,6-di(1-pyrenyl)pyridine (2,6-DPP), and 3,5-di(1-pyrenyl)-pyridine (3,5-DPP)). 0 revealed by single-crystal X-ray analysis and computational simulations, all compounds possess highly twisted conformations in the solid state with interpyrene torsional angles of 42.3 degrees-57.2 degrees. These solid-state conformations and packing variations of pyrenylpyridines could be correlated to observed variations in physical characteristics such as photo/thermal stability and spectral properties, but showed only marginal influence on electrochemical properties. The novel derivative, 2,4,6-TPP, exhibited the lowest degree of crystallinity as revealed by powder X-ray diffraction analysis and formed amorphous thin films as verified using grazing-incidence wide-angle X-ray scattering. This compound also showed high thermal/photo stability relative to its disubstituted analogues (DPPs). Thus, a nondoped organic light-emitting diode (OLED) prototype was fabricated using 2,4,6-TPP as the emissive layer, which displayed a sky-blue electroluminescence with Commission Internationale de L\u27Eclairage (CIE) coordinates of (0.18, 0.34). This OLED prototype achieved a maximum external quantum efficiency of 6.0 +/- 1.2% at 5 V. The relatively high efficiency for this simple-architecture device reflects a good balance of electron and hole transporting ability of 2,4,6-TPP along with efficient exciton formation in this material and indicates its promise as an emitting material for design of blue OLED devices

EM011 activates a survivin-dependent apoptotic program in human non-small cell lung cancer cells

<p>Abstract</p> <p>Background</p> <p>Lung cancer remains a leading cause of cancer death among both men and women in the United States. Treatment modalities available for this malignancy are inadequate and thus new drugs with improved pharmacological profiles and superior therapeutic indices are being continually explored. Noscapinoids constitute an emerging class of anticancer agents that bind tubulin but do not significantly alter the monomer/polymer ratio of tubulin. EM011, a rationally-designed member of this class of non-toxic agents, is more potent than the lead molecule, noscapine.</p> <p>Results</p> <p>Here we report that EM011 inhibited proliferation of a comprehensive panel of lung cancer cells with IC₅₀'s ranging from 4-50 μM. In A549 human non-small cell lung cancer cells, the antiproliferative activity was mediated through blockage of cell-cycle progression by induction of a transient but robust mitotic arrest accompanied by activation of the spindle assembly checkpoint. The mitotically-arrested A549 cells then override the activated mitotic checkpoint and aberrantly exit mitosis without cytokinesis resulting in pseudo G1-like multinucleated cells that either succumb directly to apoptosis or continue another round of the cell-cycle. The accumulated enormous DNA perhaps acts as genotoxic stress to trigger cell death. EM011-induced apoptotic cell death in A549 cells was associated with a decrease of the Bcl2/BAX ratio, activation of caspase-3 and cleavage of PARP. Furthermore, EM011 induced downregulation of survivin expression over time of treatment. Abrogation of survivin led to an increase of cell death whereas, overexpression caused decreased apoptosis.</p> <p>Conclusion</p> <p>These <it>in vitro </it>data suggest that EM011 mediates antiproliferative and proapoptotic activity in non-small cell A549 lung cancer cells by impeding cell-cycle progression and attenuating antiapoptotic signaling circuitries (viz. Bcl2, survivin). The study provides evidence for the potential usefulness of EM011 in chemotherapy of lung cancer.</p

Evaluation of Geometrical Nonlinear Behaviour of FRP Composite Plate Using Finite Element Method

The work presents the prediction of nonlinear behavior of a square plate made of composite material under uniform transvers pressure using 3-D finite element analysis. Transverse deflection, Normal stresses and Shear stresses are evaluated for different values of load and by varying the number of layers. The effect of loading and variation of stresses in both the analyses for different lay-up of composite laminated plate are determined. The study also includes the effect of the layer thickness for different lay-up responses of laminate under the clamped boundary conditions. The commercial Finite element analysis software ANSYS has been successfully executed for both linear Static analysis and geometric nonlinear static analysis

Closest Neighbour Search By Spatial Transformed Index

Spatial queries consolidate achieve interest andnearest neighbour recuperation offers result torequest issued customers in light of articles likeeatery, healing facilities and lodgings. In any case,rising applications including new kind of inquiriesby the customers proposing to find spatial articlesnearby additional related content. Existing IR2-treeis not giving viable spatial request result. Wepresent new framework Spatial Inverted Index it isextension of routine upset file usingmultidimensional data gives profitable spatialquestion results with less responsive time