Covalent modification of protein by drugs may disrupt self-tolerance, leading to lymphocyte activation. Until now, determination of the threshold required for this process has not been possible. Therefore, we performed quantitative mass spectrometric analyses to define the epitopes formed in tolerant and hypersensitive patients taking the β-lactam antibiotic piperacillin and the threshold required for T cell activation. A hydrolyzed piperacillin hapten was detected on four lysine residues of human serum albumin (HSA) isolated from tolerant patients. The level of modified Lys541 ranged from 2.6 to 4.8%. Analysis of plasma from hypersensitive patients revealed the same pattern and levels of modification 1–10 d after the commencement of therapy. Piperacillin-responsive skin-homing CD4+ clones expressing an array of Vβ receptors were activated in a dose-, time-, and processing-dependent manner; analysis of incubation medium revealed that 2.6% of Lys541 in HSA was modified when T cells were activated. Piperacillin–HSA conjugates that had levels and epitopes identical to those detected in patients were shown to selectively stimulate additional CD4+ clones, which expressed a more restricted Vβ repertoire. To conclude, the levels of piperacillin–HSA modification that activated T cells are equivalent to the ones formed in hypersensitive and tolerant patients, which indicates that threshold levels of drug Ag are formed in all patients. Thus, the propensity to develop hypersensitivity is dependent on other factors, such as the presence of T cells within an individual’s repertoire that can be activated with the β-lactam hapten and/or an imbalance in immune regulation.
Carnosol, a phenolic diterpene, is one of the effective anticancer agents naturally occurring in rosemary, sage, parsley, and oregano. The chemoresistance problem increased with the routinely used chemotherapy. Therefore, the efforts to find a substitute with safe and low cost have become crucial worldwide. The current study attempts to inspect the anticancer molecular mechanisms of Carnosol on modulating up- and down- regulation of multiple genetic carcinogenesis pathways. The cytotoxicity of Carnosol on Hela cells was evaluated by MTS assay. Flow cytometry was used to assess apoptosis and cell cycle arrest. The apoptotic morphological changes were obvious by dual apoptosis assay. The differential gene expression after treatment wi
... Show MoreThis article presents the results of numerical simulations performed using ABAQUS/CAE version 2019. The study aims to evaluate the structural integrity of reinforced concrete (RC) T-beams strengthened with externally bonded carbon fiber reinforcements polymer composite materials (EB) (CFRP), especially their response to bending and shear forces. The numerical model was validated by comparing the numerical and experimental results of eight RC T-beams. The numerical analysis was then extended to include various factors, including the impact of the tilt angle of the U-CFRP shell on the shear strength. The goal of this numerical extension is to implement a numerical model capable of simulating the nonlinear behavior of these beams accur
... Show MoreAs they include both nucleophilic and electrophilic moieties on the same skeleton, enaminones are an important subclass of chemical compounds that contain conjugated NC=CC=O fragments. These active sites aid in the production of organic molecules containing linear or cyclic heteroatoms. Enaminones and the chemica1 compounds produced from them are both biologically active against the most dangerous bacteria. As a result, they have been utilized as starting materials for the synthesis of anti-inf1ammatory, antibacteria1, anticonvulsant, anticancer, anti-urease, anti-malaria1, optically luminescent, corrosion inhibition, and antitumor agents. Their synthesis has usually a terrific deal of interest and a plethora of synthetic paths have been na
... Show MoreBackground: Laser is a novel physical therapy technique used to treat various conditions, including wound healing, inhibition of bacterial growth, and postoperative wounds. High-power pulsed alexandrite laser therapy is one of the most prevalent forms of laser therapy, which is a noninvasive method for treating various pathological conditions, thereby enhancing functional capacities and quality of life. It is a modern medical and physiotherapeutic technology. Generally, the Alexandrite laser emits infrared light with a wavelength of 755 nm, allowing it to propagate and penetrate tissues. Objective: This study focused on the application of a high-power pulsed alexandrite laser in vitro to evaluate the effect of a pulsed alexandrite l
... Show Morezine level in serum was mesured from patients suffering ftom cancer and healthy indiciduals hindred from each individuals were classified into three according to thier age the groups were
BACKGROUND: Cough-variant asthma (CVA) is a type of asthma in which the main symptom is a dry, non-productive cough. OBJECTIVE: The objective of the study was to evaluate the therapeutic effect of Montelukast in CVA and to investigate the prevalence of Montelukast in CVA. METHODS: A cross-sectional study was conducted on 30 patients with chronic cough at least 8 weeks using Montelukast at Al-Kindy Hospital over the period of January 2018‒March 2018. An interview using questionnaire was used to collect the data that were specifically prepared to meet the objective of study including age, sex, associated disease, exacerbation factors, and classical therapy. RESULTS: There was a reduction of the symptoms associated
... Show MoreBackground: Chronic renal failure (CRF) is a clinical syndrome that occurs when there is gradual decline in renal operation overtime.
Objective: This study aims to investigate the prevalence of depression among medical students at university of Baghdad, college of medicine in Iraq and the association between some variables and depression.
Aim: This study aimed to identify the impact of tobacco use in the etiology of chronic renal failure among Sudanese patients in Omdurman Military Hospital and Omdurman Kidney Dialysis Center
Materials and methods: This descriptive community-based study was conducted in Khartoum State. A random sample of 100 cases with chronic renal failure and 100
... Show MoreObjective: Matrix tablet approach is one of the delivery systems intended for poorly water-soluble drugs, like candesartan cilexetil (CC). CC is a class II drug used for the treatment of hypertension. Methods: Matrix tablets from (F1x to F18z) were prepared in the presence of β‑cyclodextrin. Matrix tablet formulation ensures control release of the drug and higher dissolution by β‑cyclodextrin. Fourier transform infrared spectroscopy (FTIR), and differential scanning calorimetry (DSC) were used to study compatibility. Results: The angle of repose determination showed good flow for most of the formulas, besides having good compressibility. Weight variation test for all formulas showed accepted value. Drug content measurement sho
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