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.
Piperine, a crystalline alkaloid compound isolated from Piper nigrum, piper longum, and other types of piper, has had many fabulous pharmacological advantages for preventing and treating some specific diseases, such as analgesic, anti-inflammatory, hepatoprotective, antimetastatic, antithyroid, immunomodulatory, antitumor, rheumatoid arthritis, osteoarthritis, Alzheimer's, and improving the bioavailability of other drugs. However, its potential for clinical use through oral usage is hindered by water solubility and poor bioavailability. The low level of oral bioavailability is caused by low solubility in water and is photosensitive, susceptible to isomerization by UV light, which causes piperine concentration to decrease. Many different
... Show Moreβ-Adrenergic blocking agents, mostly comprising of β-amino alcohols, are of pharmaceutical significance and have received major attention due to their utility in the management of cardiovascular disorders including hypertension, angina pectoris, cardiac arrhythmias and other disorders related to the sympathetic nervous system. Most compounds available for clinical use belong to the aryloxypropanolamine series, which is considered the second generation of β-blocking agents. The present study includes the synthesis of compounds with an N-substituted oxypropanolamine moiety attached to the 1, 3, 4-thiadiazole derivatives. According to this information, eight compounds were synthesized and characterized by IR spectra and elemental m
... Show MoreWater pollution as a result of contamination with dye-contaminating effluents is a severe issue for water reservoirs, which instigated the study of biodegradation of Reactive Red 195 and Reactive Blue dyes by E. coli and Bacillus sp. The effects of occupation time, solution pH, initial dyes concentrations, biomass loading, and temperature were investigated via batch-system experiments by using the Design of Experiment (DOE) for 2 levels and 5 factors response surface methodology (RSM). The operational conditions used for these factors were optimized using quadratic techniques by reducing the number of experiments. The results revealed that the two types of bacteria had a powerful effect on biodegradable dyes. The regression analysis reveale
... Show MoreA comparative study was done on the adsorption of methyl orange dye (MO) using non-activated and activated corn leaves with hydrochloric acid as an adsorbent material. Scanning electron microscopy (SEM) and Fourier Transform Infrared spectroscopy (FTIR) were utilized to specify the properties of adsorbent material. The effect of several variables (pH, initial dye concentration, temperature, amount of adsorbent and contact time) on the removal efficiency was studied and the results indicated that the adsorption efficiency increases with the increase in the concentration of dye, adsorbent dosage and contact time, while inversely proportional to the increase in pH and temperature for both the treated and untreated corn leav
... Show MoreThis article presents the results of an experimental investigation of using carbon fiber–reinforced polymer sheets to enhance the behavior of reinforced concrete deep beams with large web openings in shear spans. A set of 18 specimens were fabricated and tested up to a failure to evaluate the structural performance in terms of cracking, deformation, and load-carrying capacity. All tested specimens were with 1500-mm length, 500-mm cross-sectional deep, and 150-mm wide. Parameters that studied were opening size, opening location, and the strengthening factor. Two deep beams were implemented as control specimens without opening and without strengthening. Eight deep beams were fabricated with openings but without strengthening, while
... Show MoreDam break is series phenomenon that can result in fatal consequences and loss of properties. Unfortunately, the observed consequences can only be available after the dam breaks. Therefore, it is important to anticipate what will happen prior to dam break to issue suitable warning and locate the possible risk areas. This study attempts to simulate the case of dam break in Blue Nile at Roseires dam and see its consequences downstream. Roseires dam lies at a distance of 630 km south of Khartoum, Sennar dam lies at about 260 km downstream of Roseires dam. In this study hydraulic model is developed based of Hydraulic Engineering Centre (HEC), River Analysis System (RAS), and HEC- RAS. The HEC-RAS based model is calibrated and validated usi
... Show MoreInefficient wastewater disposal and wastewater discharge problems in water bodies have led to increasing pollution in water bodies. Pollutants in the river contribute to increasing the biological oxygen demand (BOD), total suspended solids (SS), total dissolved solids (TDS), chemical oxygen demand (COD), and toxic metals render this water unsuitable for consumption and even pose a significant risk to human health. Over the last few years, water conservation has been the subject of growing awareness and concern throughout the world, so this research focused on review studies of researches that studied the importance of water quality of wastewater treated disposal in water bodies and modern technology to management w
... Show MoreAccurate calculation of transient overvoltages and dielectric stresses from fast-front excitations is required to obtain an optimal dielectric design of power components subjected to these conditions, which are commonly due to switching and lightning, as well as utilization of power-electronic devices. Toroidal transformers are generally used at the low voltage level. However, recent investigations and developments have explored their use at the medium voltage level. This paper analyzes the model-based improvement of the insulation design of medium voltage toroidal transformers. Lumped and distributed parameter models are used and compared to predict the transient response and dielectric stress along the transformer winding. The parameters
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