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 current study, performed during the period from February 2021 to June 2022 at the University of Thi- Qar/ College of Education for Pure Sciences, and aimed to follow the changes in external morphological features at different Embryonic developmental stages in pregnant rats treated with different doses of amlodipine. Usage In this study, 18 pregnant rats were randomly divided into three groups, each with six pregnant rats. Each group received different concentrations of amlodipine (0.3, 0.5) in oral doses until the 20th day of gestation, while the control group was injected with 0.9% normal saline. Teratomas are bizarre tumors derived from embryonic tissue that are normally found only in the gonadal and sacral regions of adults. Primary
... Show MoreThe aim of this study is to determine the effect of cold plasma on nails pH, creatine levels and the accumulative of some trace elements in humans nails. Creatine levels in the blood, as well as pH and trace elements, were measured before and after (1, 2) months of plasma exposure in both gender (men and women) between the ages of 22 and 25 years. Nails are exposed to cold plasma with a voltage of (175 volts) and (2 gas flow). After one month of exposure, there was no significant change in the levels of all parameters, but after 2 months, the concentration of creatine and pH had reached a near- neutral value. In both men and women, calcium concentration increased and showed a positive response to cold plasma, while the v
... Show MoreABSRTACT Background: Soft liner material is become important in dental prosthetic treatment. They are applied to the surface of the dentures to achieve more equal force distribution , reduce localized pressure and improve denture retention by engaging undercut . So the aim of the study is to evaluate the effect of different surface treatment by air-abrasion AL2O3 and laser treatment with CO2 laser on improving the shear bond strength of the denture liner to acrylic denture base material . Materials and methods: the 30 specimens of heat cured acrylic denture base material (high Impact acrylic )and heat cured soft liner (Vertex ,Nether Lands )were prepared for this study .They were designed and divided according to type of the s
... Show MorePVA and chitosan biodegradable, non-toxic, biocompatible polymers convenient for use in drug release.
In this study polyvinyl alcohol (PVA) and chitosan (CS) hydrogels crosslinked with glutaraldehyde (GA) with different ratio morphology and structure characterization interpenetrating polymer network (IPN).They were investigated by Fourier transmission infrared spectroscopy (FTIR), scanning electron microscope (SEM), UV-Visible spectrophotometer,swelling of hydrogel and drug release were studied by changing crosslinking ratio and PH.
Pulsatile drug delivery systems are time-controlled dosage forms which are designed to release the active pharmaceutical ingredient after a predetermined lag time to synchronize the disease circadian rhythm. A migraine shows circadian rhythm with a marked increase in attacks between 6 a.m. and 8 a.m.
Sumatriptan is a selective agonist at serotonin (5-Hydroxy tryptamine1 (5-HT1))receptors, is an effective treatment for acute migraine attacks.
The aim of this work is to prepare time-controlled press-coated tablet with a lag time of 5.45 hrs.
Six formulas of fast dissolving core tablets and three formulas of press-coated tablets were prepared by using direct compression method using different variables to prepa
... Show MoreBackground: Tooth eruption is a more general process, however, which includes certain posteruptive tooth movements. There are two fundamental requirements for both tooth eruption to occur: (1) Require soft tissue, intervening between tooth structure and alveolar bone, which plays an important role in regulating the remodeling of adjacent tissues. (2) Require bone turnover that is temporally and spatially regulated to facilitate specific translocations of teeth through alveolar bone These amniotic stem cells are multipotent and able to differentiate into various tissues, which may be useful for human application and recently it used in many medical branches. CD34 is an endothelial marker that is extensively used in immunohistochemistry a
... Show MoreIn this review of literature, the light will be concentrated on the role of stem cells as an approach in periodontal regeneration.