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.
New Derivatives for Known P- Jactam antibiotics were
synthesized utilizing the free amino group pres nt in the parent compounds as the site for derivatization. The objectives for this study
are to have new compounds which could have an increased potential resistance to the degradative enzymes knowing to be able to destroy
the antibacterial activity of 13· lactam antibiotics- Besides. these new
derivatives could be congeners of known agents, or may be a
pott:ntial pro-drugs for thes
... Show MoreType 2 diabetes mellitus (T2DM) became the most prevalent health problem. Almost half of the world's people are ignorant that have diabetes. Menopause occurs as an important alteration in women through which take place the change in sex hormones, distribution in fat،s body, and metabolism, altogether which participate in the metabolism disease such as type 2 diabetes mellitus. Several studies have appeared the association between the TCF7L2 gene and different diseases like type 2 diabetes mellitus (T2DM). This study aimed to detect the relation of the genetic variation polymorphism for the TCF7L2 gene (rs12255372 G/T) in Iraqi women menopausal with T2DM. The outcomes indicated the increased levels of biochemical characteristics including H
... Show MoreAccurate description of thermodynamic, structural, and electronic properties for bulk and surfaces of ceria (CeO2) necessitates the inclusion of the Hubbard parameter (U) in the density functional theory (DFT) calculations to precisely account for the strongly correlated 4f electrons. Such treatment is a daunting task when attempting to draw a potential energy surface for CeO2-catalyzed reaction. This is due to the inconsistent change in thermo-kinetics parameters of the reaction in reference to the variation in the U values. As an illustrative example, we investigate herein the discrepancy in activation and reaction energies for steps underlying the partial and full hydrogenation of acetyl
... Show MoreTook apple branches Genuine and Architecture tissue cultured in vitro 3 cm long and planted in the middle of food MS that contains different concentrations of inorganic salts and of Mntmat free growth and incubated Transplanter to study their effect on rooting Aalavra
Background: Accurate measurement of a patient’s height and weight is an essential part of diagnosis and therapy, but there is some controversy as to how to calculate the height and weight of patients with disabilities. Objective: This study aims to use anthropometric measurements (arm span, length of leg, chest circumference, and waist circumference) to find a model (alternatives) that can allow the calculation of the height and the body weight of patients with disabilities. Additionally, a model for the prediction of weight and height measurements of patients with disabilities was established. Method: Four hander patients aged 20-80 years were enrolled in this study and divided into two groups, 210 (52.5%) male and 190 (47.5%) fe
... Show MoreAge, hypertension, and diabetes can cause significant alterations in arterial structure and function, including changes in lumen diameter (LD), intimal-medial thickness (IMT), flow velocities, and arterial compliance. These are also considered risk markers of atherosclerosis and cerebrovascular disease. A difference between right and left carotid artery blood flow and IMT has been reported by some researchers, and a difference in the incidence of nonlacunar stroke has been reported between the right and left brain hemispheres. The aim of this study was to determine whether there are differences between the right and left common carotid arteries and internal carotid arteries in patient
Itraconazole (ITZ) is an antifungal drug (BCSII) used for the treatment of local and systemic fungal infections. Furthermore, ITZ used as an antifungal prophylaxis for immunocompromised patients.
The objective of the study is to overcome the two problems of low and pH dependent solubility of ITZ by its preparation as floating microparticles.
Firstly, pH-dependent floating microparticles were prepared using oil in water solvent evaporation method, from which the best one (F7) selected as a best pH-dependent formula with composition of ITZ (200mg),EC (800mg), HPMC 15cps (200mg) and safflower oil (2ml) .Then, F7 was compared with the selected Relatively pH-independent ITZ floating microparticles formula wit
... Show MoreSelexipag is an orally selective long-acting prostacyclin receptor agonist, which indicated for the treatment of pulmonary arterial hypertension. It is practically insoluble in water ( class II, according to BCS). This work aims to prepare and optimized Selexipag nanosuspensions to achieve an enhancement in the in vitro dissolution rate. The solvent antisolvent precipitation method was used for the production of nanosuspension, and the effect of formulation parameters (stabilizer type, drug: stabilizer ratio, and use of co-stabilizer) and process parameter (stirring speed) on the particle size and polydispersity index were studied. SLPNS prepared with Soluplus® as amain stabilizer (F15) showed the smallest particle size 47nm wi
... Show MoreBackground: Entamoeba histolytica is the causative agent of amoebic dysentery and hepatic abscesses. Despite the efficacy of metronidazole in alleviating infectious diseases, the global dissemination of drug-resistant parasites raises the possibility that Punica granatum could serve as an effective natural alternative treatment. Objective: To evaluate the effect of P. granatum methanolic and aqueous extracts of various parts against E. histolytica trophozoites in an in vitro setting. Methods: Various concentrations (0.14, 0.7, 1.4, and 2.8 mg/ml) of P. granatum extracts of the flowers, leafs, peels, and seeds were chosen for this purpose. A culture medium containing 0.05x106/ml E. histolytica trophozoites was treated with different
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