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.
A simple, cheap, fast, accurate, Safety and sensitive spectrophotometric method for the determination of sulfamethaxazole (SFMx), in pure form and pharmaceutical dosage forms. has been described The Method is based on the diazotization of the drug by sodium nitrite in acidic medium at 5Cº followed by coupling with salbutamol sulphate (SBS) drug to form orange color the product was stabilized and measured at 452 nm Beer’s law is obeyed in the concentration range of 2.5-87.5 ?g ml-1 with molar absorptivity of 2.5x104 L mole-1 cm-1. All variables including the reagent concentration, reaction time, color stability period, and sulfamethaxazole /salbutamol ratio were studied in order to optimize the reaction conditions. No interferences were
... Show MoreA first step in this research was to synthesize Schiff's bases(1-3)using an Amoxcilline intensification reaction with different aromatic aldehydes in absolute ethanol. In benzene and refluxing conditions,Schiff's bases were cyclized with succinic and Phthalic anhydride to give a new sequence of 1,3-oxazepine derivatives(4-6) and (7-9),respectively.The last step,cyclization reactions with sodium azide in THF solvent resulted in the formation of [10 and 11], which are supposed to be biologically significant.FT.IR, 1H-NMR and 13C-NMR (for compound 4,7,9, and 11),as well as melting points reported, were used to characterize these prepared compounds ,Bacillus (G+), Staphylococcus (G+), and E.Coli (G-)were screened against these compounds. . To i
... Show MoreAS Salman, SK Hameed…, Karbala Journal of Physical Education Sciences, 2020
The research aims to identify the theoretical foundations for measuring and analyzing quality costs and continuous improvement, as well as measuring and analyzing quality costs for the Directorate of Electricity Supply / Middle Euphrates and continuous improvement of the distribution of electrical energy,The problem was represented by the high costs of failure and waste in electrical energy result to the excesses on the network and the missing (lost) energy,Thus, measuring and analyzing quality costs for the distribution of electrical energy and identifying continuous improvement leads to a reduction in missing and an increase in sales, as the research reached many conclusions, the most important of which is the high percentage o
... Show MoreBackground. Endodontic infections caused by remaining biofilm following disinfection with chemical fluids encourage secondary bacterial infection; hence, employing laser pulses to activate the fluids is advised to improve microbial biofilm clearance. This study investigated the performance of Er,Cr:YSGG laser in photon-induced photoacoustic streaming (PIPS) agitation of 5.25% sodium hypochlorite (NaOCl) to enhance the removal of mature Enterococcus faecalis (E. faecalis) biofilms in complex root canal systems. Methods. The mesial roots of the lower first and second molars were separated and inoculated with E. faecalis bacteria for 30 days. The roots were irrigated with 5.25% NaOCl, some of them were agitated with passive ultrasonic
... Show MoreObjective: Develop a deliberate thinking scale for the setting skill in volleyball for second-year female students in the College of Physical Education and Sports Sciences for Woman. Research methodology: The researchers used the experimental approach, employing a two-group approach (pre-test and post-test), to suit the nature of the research. The research community comprised (65) second-year female students from the College of Physical Education and Sports Sciences for Woman at the University of Baghdad for the academic year 2024-2025. The research sample was randomly selected, with (15) students in Section A, the experimental group, and (15) students in Section B, the control group. This group represented (46%) of the students. Th
... Show MoreObjective: Develop a deliberate thinking scale for the setting skill in volleyball for second-year female students in the College of Physical Education and Sports Sciences for Woman. Research methodology: The researchers used the experimental approach, employing a two-group approach (pre-test and post-test), to suit the nature of the research. The research community comprised (65) second-year female students from the College of Physical Education and Sports Sciences for Woman at the University of Baghdad for the academic year 2024-2025. The research sample was randomly selected, with (15) students in Section A, the experimental group, and (15) students in Section B, the control group. This group represented (46%) of the students. Th
... Show MoreThe central nervous system is the most important system and is very sensitive to any accidental infection during ontogenesis; it includes brain and spinal cord. The cerebellum is the second largest part of the brain after cerebrum and it’s very sensitive to the abnormal changes during the embryological development. This study was designed to investigate the effect of the maternal exposure of selected concentrations of suspension of nanoparticles on the ontogenesis of the rat cerebellum after embryos implanted in uterus. A total of 60 female pregnant rats were divided in to three groups, each contains 20 females. Group1 (G1) was treated orally with 2mg/kg /body weight (b. wt) of suspension of silver nanoparticles (Ag NPs). While group 2 (G
... Show More