Drug hypersensitivity involves the activation of T cells in an HLA allele–restricted manner. Because the majority of individuals who carry HLA risk alleles do not develop hypersensitivity, other parameters must control development of the drug-specific T cell response. Thus, we have used a T cell–priming assay and nitroso sulfamethoxazole (SMX-NO) as a model Ag to investigate the activation of specific TCR Vβ subtypes, the impact of programmed death -1 (PD-1), CTL-associated protein 4 (CTLA4), and T cell Ig and mucin domain protein-3 (TIM-3) coinhibitory signaling on activation of naive and memory T cells, and the ability of regulatory T cells (Tregs) to prevent responses. An expansion of the TCR repertoire was observed for nine Vβ subtypes, whereas spectratyping revealed that SMX-NO–specific T cell responses are controlled by public TCRs present in all individuals alongside private TCR repertoires specific to each individual. We proceeded to evaluate the extent to which the activation of these TCR Vβ–restricted Ag-specific T cell responses is governed by regulatory signals. Blockade of PD-L1/CTLA4 signaling dampened activation of SMX-NO–specific naive and memory T cells, whereas blockade of TIM-3 produced no effect. Programmed death-1, CTLA4, and TIM-3 displayed discrete expression profiles during drug-induced T cell activation, and expression of each receptor was enhanced on dividing T cells. Because these receptors are also expressed on Tregs, Treg-mediated suppression of SMX-NO–induced T cell activation was investigated. Tregs significantly dampened the priming of T cells. In conclusion, our findings demonstrate that distinct TCR Vβ subtypes, dysregulation of coinhibitory signaling pathways, and dysfunctional Tregs may influence predisposition to hypersensitivity.
Objective: The objective of this study was to prepare nanosuspension of a practical water insoluble antiulcer drug which is lafutidine to enhance the solubility, dissolution rate with studying the effect of different formulation variables to obtain the best formula with appropriate physical properties and higher dissolution rate.Methods: Nanosuspension of lafutidine was prepared using solvent anti-solvent precipitation method using Polyvinylpyrrolidone K-90(PVP K-90) as the stabilizer. Ten formulations were prepared to show the effect of different variables in which two formulations showed the effect of stabilizer type, three formulations showed the effect of stabilizer concentration, two formulations showed the effect of combinatio
... Show MoreA Novel artificial neural network (ANN) model was constructed for calibration of a multivariate model for simultaneously quantitative analysis of the quaternary mixture composed of carbamazepine, carvedilol, diazepam, and furosemide. An eighty-four mixing formula where prepared and analyzed spectrophotometrically. Each analyte was formulated in six samples at different concentrations thus twentyfour samples for the four analytes were tested. A neural network of 10 hidden neurons was capable to fit data 100%. The suggested model can be applied for the quantitative chemical analysis for the proposed quaternary mixture.
In this review, previous studies on the synthesis and characterization of the metal Complexes with paracetamol by elemental analysis, thermal analysis, (IR, NMR and UV-Vis (spectroscopy and conductivity. In reviewing these studies, the authors found that paracetamol can be coordinated through the pair of electrons on the hydroxyl O-atom, carbonyl O-atom, and N-atom of the amide group. If the paracetamol was a monodentate ligand, it will be coordinated by one of the following atoms O-hydroxyl, O-carbonyl or N-amide. But if the paracetamol was bidentate, it is coordinated by atoms (O-carbonyl and N-amide), (O-hydroxyl and N-amide) or (O-carbonyl and O-hydroxyl). The authors also found that free paracetamol and its complexes have antimicrobial
... Show MoreA Novel artificial neural network (ANN) model was constructed for calibration of a multivariate model for simultaneously quantitative analysis of the quaternary mixture composed of carbamazepine, carvedilol, diazepam, and furosemide. An eighty-four mixing formula where prepared and analyzed spectrophotometrically. Each analyte was formulated in six samples at different concentrations thus twenty four samples for the four analytes were tested. A neural network of 10 hidden neurons was capable to fit data 100%. The suggested model can be applied for the quantitative chemical analysis for the proposed quaternary mixture.
In this review, previous studies on the synthesis and characterization of the metal Complexes with paracetamol by elemental analysis, thermal analysis, (IR, NMR and UV-Vis (spectroscopy and conductivity. In reviewing these studies, the authors found that paracetamol can be coordinated through the pair of electrons on the hydroxyl O-atom, carbonyl O-atom, and N-atom of the amide group. If the paracetamol was a monodentate ligand, it will be coordinated by one of the following atoms O-hydroxyl, O-carbonyl or N-amide. But if the paracetamol was bidentate, it is coordinated by atoms (O-carbonyl and N-amide), (O-hydroxyl and N-amide) or (O-carbonyl and O-hydroxyl). The authors also found that free paracetamol and its complexes have antimicrobial
... Show MoreSolubility problem of many of effective pharmaceutical molecules are still one of the major obstacle in theformulation of such molecules. Candesartan cilexetil (CC) is angiotensin II receptor antagonist with very low water solubility and this result in low and variable bioavailability. Self- emulsifying drug delivery system (SEDDS) showed promising result in overcoming solubility problem of many drug molecules. CC was prepared as SEDDS by using novel combination of two surfactants (tween 80 and cremophore EL) and tetraglycol as cosurfactant, in addition to the use of triacetin as oil. Different tests were performed in order to confirm the stability of the final product which includes thermodynamic study, determination of self-emulsificat
... Show MoreNovel artificial neural network (ANN) model was constructed for calibration of a multivariate model for simultaneously quantitative analysis of the quaternary mixture composed of carbamazepine, carvedilol, diazepam, and furosemide. An eighty-four mixing formula where prepared and analyzed spectrophotometrically. Each analyte was formulated in six samples at different concentrations thus twentyfour samples for the four analytes were tested. A neural network of 10 hidden neurons was capable to fit data 100%. The suggested model can be applied for the quantitative chemical analysis for the proposed quaternary mixture.
Transparency considered being one of the modern administrational terms which started to be largely used in the last period, because of its political, economical, social and cultural dimensions. As well as, its administrational dimension that helps to create a work environment marked by order and flawless from wrong practices and Transparency provides credibility to the sides that pursue it in their practices, till it became a mean of distinction. The choice of the subject of the research ((Transparency and its effect on Level of Job satisfactions of Workers in General Insurance company)), which aims to measure the effect of Transparency in Level of Job satisfactions of Workers in Insurance company. Came in the time when many countries te
... Show MoreBackground: to evaluate the effect of different dentifrices on the surface roughness of two composite resins (nanofilled-based and nanoceramic – based composite resins). Materials and methods: Forty specimens (diameter 12 mm and height of 2mm) prepared from different composite resin materials: Z350 (nanofilled composite, and Ceram-X (nanoceramic) .they were subjected to brushing simulation equivalent to the period of 1 year. The groups assessed were a control group brushed with distilled water (G1), Opalescence whitening toothpasteR (G2), Colgate sensitive pro-relief (G3) and Biomed Charcoal Toothpaste (G4). The initial and final roughness of each group was tested by surface roughness tester. The results were statistically analyzed using
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