Advantage of Natural Barrier in Locating Intake In River an Example Study

Source: ICHE Conference Archive - https://mdi-de.baw.de/icheArchiv

Transition Metal Carbohydrazide Nitrates: Burn-rate Modifiers for Propellants

This paper discusses the synthesis and characterisation of cobalt (Co), nickel (Ni) andcopper (Cu) carbohydrazide nitrates. In differential scanning calorimetry (DSC), the complexesexhibited exothermic decomposition indicating their energetic nature. The commencement ofdecomposition was observed at 220 °C for Ni complex, and at 160 °C for Co complex whereasthat of Cu complex occurred at 75 °C. In view of the better thermal stability, Ni and Co complexeswere selected for further study. The activation energy of decomposition of Ni and Co complexeswere found to be 47 kcal/mol and 60 kcal/mol respectively. Impact and friction sensitivity testresults revealed relatively lower vulnerability of carbohydrazide cobalt nitrate. Its incorporationin an ammonium perchlorate (AP)-based composite propellant led to 9-19 per cent enhancementwhereas that of carbohydrazide nickel nitrate resulted in 28-74 per cent enhancement in burningrates in the pressure range 1.9 MPa to 8.8 MPa. Exothermic decomposition of the coordinationcomplexes on propellant surface and involvement of metal at molecular level formed ondecomposition of the complexes in combustion environment of composite propellant may beattributed to the catalytic effect of this class of compounds on the lines of reported literature

Photophysics of some styryl thiazolo quinoxaline dyes in organic media

The photophysics of a new class of styryl dyes, 2-styryl thiazolo quinoxaline (STQ) based structures was investigated in organic solvents and organized molecular assemblies. The absorption, steady state and time-resolved fluorescence characteristics of the STQ dyes in low-viscosity organic solvents are consistent with a single species in the ground and excited state. The one electron electrochemical oxidation and reduction potentials of the dyes are within ±1V vs. NHE. The spectral shifts of the dyes in organic solvents are linearly correlated with the variation of solvent polarity parameters. The dipole moments in the ground and excited state of the dyes were calculated without assuming a value for the cavity radius. The temperature dependence of the nonradiative rate of STQ dye in DMSO indicated an activation barrier (ΔE=10.7 kJ/mol) which is comparable to the activation energy (Ea=13.7 kJ/mol) of viscous friction in DMSO. In dichloromethane, the activation barrier is 34.0 kJ/mol which is very high compared to Ea=6.64 kJ/mol. Formation of a dye–solvent complex is suggested in dichloromethane. The fluorescence decay of STQ dye is multiexponential in a viscous solvent (2-octanol) or when bound to a protein (Lysozyme), micelle or lipid membrane. In 2-octanol, the decay parameters are wavelength dependent and the results are consistent with the mechanism of excited state kinetics of solvent relaxation. In other systems, the multiexponential decay is due to multiple sites of solubilization of the dye in the organized molecular assembly

Bilateral synchronous spermatocytic seminoma: a rare case report from rural India and literature review

Spermatocytic Seminoma is an unusual germ cell tumour known to arise from testis only. It is associated with good prognosis. Testicular tumours as such are uncommon in Asia as compared to western countries. In the literature only five cases of bilateral synchronous Spermatocytic Seminoma have been reported. Fifty years male patient presented to us with bilateral scrotal swelling and evaluation revealed neoplastic aetiology of bilateral testicular enlargement. Left side radical orchidectomy was performed initially which histopathologically revealed spermatocytic seminoma. Subsequently right side radical orchidectomy was performed after intra-op frozen section confirmation of neoplastic nature. Histopathology revealed same pathology as on left side. Immunohistochemistry of specimen from both testes was again conclusive of spermatocytic seminoma. We hereby report this rare case of Bilateral Synchronous Spermatocytic Seminoma. This is the first case report from entire Asian continent except for Japan.Pan African Medical Journal 2012; 13:3

Simultaneous estimation of simvastatin and labetalol in bulk and solid dosage form

A simple, accurate, precise, sensitive, and highly selective ultra violet spectrometer method has been developed for the simultaneous estimation of simvastatin and labetalol in bulk and solid dosage form. The estimation of simvastatin was carried out at 239 nm while labetalol was estimated at 222.4 nm. The developed method was validated for linearity range, precision, recovery studies and interference study for mixture, all these parameter showed the adaptability of the method for the method quality analysis of the drug in bulk and combination formulation. Keywords: Simvastatin, Labetalol, UV Spectrophotometric, Dosage form

TITLE PAGE α-AMINOAZAHETEROCYCLIC-METHYLGLYOXAL ADDUCTS DO NOT INHIBIT CFTR CHLORIDE CHANNEL ACTIVITY

ABSTRACT Inhibitors of the cystic fibrosis transmembrane conductance regulator (CFTR) chloride channel have potential applications in the therapy of secretory diarrheas and polycystic kidney disease. Recently, several highly polar α-aminoazaheterocyclic-methylglyoxal adducts were reported to reversibly inhibit CFTR chloride channel activity with IC50 values in the low picomolar range (Routaboul et al. J. Pharmacol. Exp. Ther. 322:1023-1035, more than 10,000-fold better than that of thiazolidionone and glycine hydrazide CFTR inhibitors identified previously by highthroughout screening. Here, we resynthesized and evaluated the α-aminoazaheterocyclicmethylglyoxal adducts of Routaboul et al. reported to have high CFTR inhibition potency (compounds 5, 7 and 8). We verified that the reported synthesis procedures produced the target compounds in high yield. However, we found that these compounds did not inhibit CFTR chloride channel function in multiple cell lines at up to 100 µM concentration, using three independent assays of CFTR function including short-circuit current analysis, whole-cell patch-clamp and YFPfluorescence quenching. As positive controls, near 100% CFTR inhibition was found by thiazolidionone and glycine hydrazide CFTR inhibitors. Our data provide direct evidence against CFTR inhibition by α-aminoazaheterocyclic-methylglyoxal adducts

Characterization of CDK(5) Inhibitor, 20-223 (aka CP668863) for Colorectal Cancer Therapy

Colorectal cancer (CRC) remains one of the leading causes of cancer related deaths in the United States. Currently, there are limited therapeutic options for patients suffering from CRC, none of which focus on the cell signaling mechanisms controlled by the popular kinase family, cyclin dependent kinases (CDKs). Here we evaluate a Pfizer developed compound, CP668863, that inhibits cyclin-dependent kinase 5 (CDK5) in neurodegenerative disorders. CDK5 has been implicated in a number of cancers, most recently as an oncogene in colorectal cancers. Our lab synthesized and characterized CP668863 – now called 20-223. In our established colorectal cancer xenograft model, 20-223 reduced tumor growth and tumor weight indicating its value as a potential anti-CRC agent. We subjected 20-223 to a series of cell-free and cell-based studies to understand the mechanism of its anti-tumor effects. In our hands, in vitro 20-223 is most potent against CDK2 and CDK5. The clinically used CDK inhibitor AT7519 and 20-223 share the aminopyrazole core and we used it to benchmark the 20-223 potency. In CDK5 and CDK2 kinase assays, 20-223 was ~3.5-fold and ~65.3-fold more potent than known clinically used CDK inhibitor, AT7519, respectively. Cell-based studies examining phosphorylation of downstream substrates revealed 20-223 inhibits the kinase activity of CDK5 and CDK2 in multiple CRC cell lines. Consistent with CDK5 inhibition, 20-223 inhibited migration of CRC cells in a wound-healing assay. Profiling a panel of CRC cell lines for growth inhibitory effects showed that 20-223 has nanomolar potency across multiple CRC cell lines and was on an average \u3e2-fold more potent than AT7519. Cell cycle analyses in CRC cells revealed that 20-223 phenocopied the effects associated with AT7519. Collectively, these findings suggest that 20-223 exerts anti-tumor effects against CRC by targeting CDK 2/5 and inducing cell cycle arrest. Our studies also indicate that 20-223 is a suitable lead compound for colorectal cancer therapy

Role of CFTR expressed by neutrophils in modulating acute lung inflammation and injury in mice

Objective and designCystic fibrosis transmembrane conductance regulator (CFTR) regulates infection and inflammation. In this study, we investigated whether a lack of functional CFTR in neutrophils would promote lipopolysaccharide (LPS)-induced lung inflammation and injury.Materials and methodsCFTR-inhibited or F508del-CFTR-mutated neutrophils were stimulated with LPS and cultured to evaluate production of cytokines and NF-κB activation. Wild-type mice were reconstituted with F508del neutrophils or bone marrow and then intratracheally challenged with LPS to observe lung inflammatory response.ResultsPharmacologic inhibition and genetic mutation of CFTR in neutrophils activated NF-κB and facilitated macrophage inflammatory protein-2 (MIP-2) and tumor necrosis factor-α (TNF-α) production. Wild-type mice reconstituted with F508del neutrophils and bone marrow had more severe lung inflammation and injury after LPS challenge compared to wild-type mice receiving wild-type neutrophils or bone marrow reconstitution.ConclusionsLack of functional CFTR in neutrophils can promote LPS-induced acute lung inflammation and injury