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.
Silybum marianum, from which silymarin (SM) is extracted, is a medicinal herb. In the Biopharmaceutics Classification System, it is of the class II type, meaning it is almost completely insoluble in water. It has a number of therapeutic properties, including anti-inflammatory as well as properties that promote wound healing.
This research target is to promote the dissolution and solubility of SM by employing a technique called solid dispersion and then incorporating the formula of solid dispersion into a topical gel that can be used for wound healing.
Solid dispersion is a technique used to enhance solubility and dissolve pharmaceuticals that are not water-soluble. This method is widely used because of its low cos
... Show MoreAlpha shape theory for 3D visualization and volumetric measurement of brain tumor progression using magnetic resonance images
In this work, a vertical pulsating heat pipe heat exchanger (PHPHE) was designed for waste heat recovery, exchanging thermal energy between two air streams in a counterflow configuration. The heat exchanger consists of six rows, each row consists of one pulsating heat pipe (PHP), and each PHP has six turns. The working fluid used in the heat pipe was acetone with fill ratios of 50%, 60%, and 70%. The effect of evaporator inlet temperature at 40, 45, and 50°C and air velocity at 0.5, 0.7, and 0.9 m/s on the pulsating heat pipes consisting of three sections- evaporator, condenser, and adiabatic, whose dimensions were 25 x 25 x 10 cm, was studied. At the same time, the condenser temperature was maintained at 26°C. The system’s th
... Show MoreAs a result of rapid industrialization and population development, toxic chemicals have been introduced into water systems in recent decades. Because of its excellent efficiency and simple design, the three-dimensional (3D) electro-Fenton method has been used for the treatment of wastewater. The goal of the current study is to explore the efficiency of phenol removal by the 3D electro-Fenton process, which is one of the advanced oxidation processes (AOPs). In the present work, the effect of the addition of granular activated carbon (GAC) particles to the electro-Fenton system as the third electrode would be investigated in the presence of graphite as the anode and nickel foam as the cathode, which is the source of electro-generated hydrogen
... Show MoreA simple, low cost and rapid flow injection turbidimetric method was developed and validated for mebeverine hydrochloride (MBH) determination in pharmaceutical preparations. The developed method is based on forming of a white, turbid ion-pair product as a result of a reaction between the MBH and sodium persulfate in a closed flow injection system where the sodium persulfate is used as precipitation reagent. The turbidity of the formed complex was measured at the detection angle of 180° (attenuated detection) using NAG dual&Solo (0-180°) detector which contained dual detections zones (i.e., measuring cells 1 & 2). The increase in the turbidity of the complex was directly proportional to the increase of the MBH concentration
... Show MoreThe time spent in drilling ahead is usually a significant portion of total well cost. Drilling is an expensive operation including the cost of equipment and material used during the penetration of rock plus crew efforts in order to finish the well without serious problems. Knowing the rate of penetration should help in speculation of the cost and lead to optimize drilling outgoings. Ten wells in the Nasiriya oil field have been selected based on the availability of the data. Dynamic elastic properties of Mishrif formation in the selected wells were determined by using Interactive Petrophysics (IP V3.5) software based on the las files and log record provided. The average rate of penetration and average dynamic elastic propert
... Show MoreThe involvement of maxillofacial tissues in SARS‐CoV‐2 infections ranges from mild dysgeusia to life‐threatening tissue necrosis, as seen in SARS‐CoV‐2‐associated mucormycosis. Angiotensin‐converting enzyme 2 (ACE2) which functions as a receptor for SARS‐CoV‐2 was reported in the epithelial surfaces of the oral and nasal cavities; however, a complete understanding of the expression patterns in deep oral and maxillofacial tissues is still lacking.
The immunohistochemical expression of ACE2 was analyzed in 95 specimens from maxillofacial tissues and 10 specimens o