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.
Nisoldipine (NSD) is a dihydropyridine class of calcium channel blockers used for hypertension treatment, it belongs to class II BCS (low solubility with high permeability), its absolute bioavailability is only 5% due to presystemic metabolism in the gut wall. It is also a substrate for a CYP3A and P-gp. Bilosomes are lipid bilayer vesicles incorporating bile salts in their walls to prevent degredation by GIT bile salts. The aim of this study is to prepare nisoldipine bilosomes as vesicular carrier and assess the effect of different formulation variables such as type of surfactant, amount of cholesterol, surfactant and sonication time on particle size, entrapment efficiency and poly dispersity index of the prepared bilos
... Show MoreThis study tries to clear the correlation and association between asthma, obesity and leptin levels. Also it will work to indicate the main risk factors which play role in the elevation of leptin level within asthmatic patients. This is a case control study conducted on (38) asthmatic patients and (20) healthy control who were closely similar by age, gender and BMI. The main statistical tests used were student t test, linear regression test and correlation test. Significance was set at P < 0.05. Sampling method used for this study was convenience sampling method. The main results of this study show a significant association and positive correlation between age (old age ≥ 40 ye
... Show MoreABSTRACT
The research aims to know the reality of a two examined variables at the organization studied identifying the relationship between managerial processes reengineering and organizational citizenship behavior. The research applied on the Electronic Manufacturing Company encompassing a sample of managers and employees consisted of (100) individuals. A questionnaire is the main instrument for data gathering, which has been included (45) questions as well as personal interviews to support the questionnaire's questions and to achieve greater realism for collecting information.
Answers were analyzed to reach the final results through the use of a number of statistical methods via
... Show MoreIn this paper, we calculate the electron energy distribution function (EEDF) and transport parameters including the electron mean energy, mobility, drift velocity and diffusion coefficient for the gas mixtures of the H2 and N2 using the EEDF program. It is concentrated on the effect of assorted concentrations of the mixtures on the EEDF and the electron transport coefficients. The work exhibits the variation amongst the different mixtures on the EEDF and the transport parameter. The results are graphically offered and discussed. In this concept, it is shown that for each mixture has a specific impact on EEDF and the transport parameter. The important of this study comes from the usage of these mix
... Show MoreFor many years it was argued that there may be a gender differences in adverse drug reactions (ADRs). This assumption was based on many possible factors such as hormonal or behavior differences, and it was not clearly identified since the female gender was not preferred to be enrolled in many clinical trials. The primary aim of this study was to assess the extent of possibly relevant gender differences in drug–ADRs regarding causality, severity, preventability, seriousness, expectedness and outcome. While the secondary aim was to assess for which group of drugs and for which ADRs gender differences are identified most often. The study was a retrospective one that depends on processing a specially selected group of data obtained from th
... Show MoreObjectives: The purpose of this in vitro study was to compare the effect of adding poloxamer surfactant to irrigant solutions on the penetration de..
The assessment of a river water’ quality is an essential procedure of monitor programs and isused to collect basic environmental data. The management of integrated water resources in asustainable method is also necessary to allow future generations to meet their water needs. Themain objective of this research is to assess the effect of the Diyala River on Tigris River waterquality using Geographic Information System (GIS) technique. Water samples have beencollected monthly from November 2017 to April 2018 from four selected locations in Tigris andDiyala Rivers using the grab sampling method. Fourteen parameters were studied which areTurbidity, pH, Dissolved Oxygen, Biological Oxygen Demand, Electrical Conductivity, TotalDissolved Solids,
... Show MoreLength of plasma generated by dc gas discharge under different vacuum pressures was studied experimentally. The cylindrical discharge tube of length 2m was evacuated under vacuum pressure range (0.1-0.5) mbar at constant external working dc voltage 1500V. It was found that the plasma length (L) increased exponentially with increasing of background vacuum air pressure. Empirical equation has been obtained between plasma length and gas pressure by using Logistic model of curve fitting. As vacuum pressure increases the plasma length increases due to collisions, ionizations, and diffusions of electrons and ions.