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.
The study was conducted in the poultry field, College of Agriculture, Al-Muthanna University from 1/3/2018 to 6/4/2018 to determine the effect of commercial Ascomax powder produced from seaweed (Ascophyllum nodocum) on some productive performance of broilers. A total of 400, one day, Ross 308 broiler chicks were used for 35 days. The chicks were randomly distributed to 4 treatments, four replicates per treatment (25 chick / replicate). The treatments were as follows: T1: (control treatment), while T2, T3 and T4 added diet by Ascomax powder by 1, 1.5 and 2 g per 1 kg of the basal diet, respectively. The results of the study showed a significant superiority (P <0.05) for the added Ascomax powder treatments compared to the treatment of control
... Show MoreThe purpose of present study is to evaluate the effect of co-administration of curcumin (CUR) at various doses on the pharmacokinetic (PK) profile of tacrolimus (TAC), a CYP 3A4 substrate in healthy male rabbits. Healthy male rabbits (n=18) were employed in an in vivo, parallel-randomized study. Three groups of rabbits were selected and separated: The rabbits in the first group (control group) received 1 mg/kg TAC orally. Blood samples (1.5-2 mL) were drawn from rabbits' ear marginal veins at the following time frames: 15.0, 30.0, 45.0, 60.0, 90.0, 120.0, 150.0, 180.0 and 300 minutes after TAC administration post dosing and analyzed by using a TAC chemiluminescent enzyme immunoassay (CLIA) detection kit. In the second and third gro
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The research attempted to find an explanation and solution to a problem related to the fluctuation and decrease In the rate of return on assets for the research sample banks during the duration of the research, The search started from the hypothesis that, The effect of salary Domiciliation on the banking profitability of a sample of Iraqi banks participating in the salary settlement system for the period (2016-2019),The research used the descriptive historical approach, the quantitative analytical approach and the statistical approach. The research reached a set of conclusions, the most important of which is The effect of salary Domiciliation on banking profitability was achieved in three banks
... Show MoreThis study was conducted on the effect of the sedimentary source (the sediments coming from both the Iraqi-Iranian borderline and the Tigris river) on the optical and textural features, especially sphericity and roundness of feldspar minerals (potassium and plagioclase types) in soils of the southern part of the alluvial plain. Eight pedons were selected to represent the study area, five of them represented sediments coming from the borderline, which included pedons of (Badra, Taj Al-Din, Al-Shihabi, Jassan, and Galati), while two of them represent the sediments of the Tigris River (Essaouira, Al-Dabouni), the pedon of Ali Al-Gharbi was represented the mixing area of sediments of all the floods coming from the borderline and the sediments o
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The present investigation aimed to formulate a liquid self-microemulsifying drug delivery system (SMEDDS) of tacrolimus to enhance its oral bioavailability by improving its dispersibility and dissolution rate. Four liquid SMEDDS were prepared using maisine CC as oil phase, labrasol ALF as surfactant and transcutol HP as co-surfactant based on the solubility studies of tacrolimus in these components. The phase behavior of the components and the area of microemulsion were evaluated using pseudoternary phase diagrams. The formulations were also assessed for thermodynamic stability, robustness to dilution, self-emulsification time, drug content, globule size and polydispersity index. The prepared SMEDDS formulations exhibi
... Show MoreThis research investigates the meanings and significance of the verse and the concluded educational purports. The expression “And in the heaven is your provision” signifies the deism of Allah. This research introduces the what have been said by Quran Explainers about meaning of Heaven & Provision. It introduces also the meaning of the sentence “which you are promised” and its concluded educational purports. This research discuses the role of educational institutions as well as the family and mosques in connecting Muslims and their children with the promise given by Allah.
Provision is guaranteed for all people if moral and material causes have been considered.
Key Words:
Purports – Educational – Co
... Show MoreThe high bounce activity according to the fosbery way is regarded as of the difficult sports concerning its way of training and perfection due to hard technique of its performance on one hand and because it depends on the player’s ability to overcome body weight resistance against the gravity. In addition to the strong ability to control the body posture when leaving the land and flying over the barrier. This activity needs to high plosion power at the moment of bouncing and this plosion depends on the period of bouncing, so the two researchers aimed to use a mechanical bouncing platform and an electronic one through several training by one foot and both feet in different directions and positions in order to reduce the time of bouncing an
... Show MoreGymnastics is one of the most interesting games in terms of organizing various world championships and tournaments. Their basic skills and their technical development, especially those with high difficulty levels that rely on basic and complex skills, are the basic skills of gymnastics are the main pillar to be developed and therefore high-difficulty skills will not depend on basic skills, which should reach the stage of the automatic mechanism. Retention) in order to move on to training and developing another skill for the difficulty of movements as well as the smooth flow of performance, ie the degrees of difficulty of each skill specific to your gym and The researcher used the experimental method and The research community determin
... Show MoreCutaneous leishmaniasis is a disease caused by Leishmania tropica parasite. Current treatments for this parasite are undesirable because of their toxicity, resistance, and high cost. Macrophages are key players against pathogens. Nitric oxide (NO), a molecule produce by immune cells, controls intracellular killing of pathogens during infection. Silver nanoparticles (Ag NPs) demonstrated broad-spectrum activity against various types of infectious diseases. It has the ability to stimulate oxygen species production. This study aims to analyze the macrophages activation through NO production and estimate the cytotoxicity based on the lactate dehydrogenase (LDH) release upon exposure to L. tropica and
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