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.
Objective: Carbamazepine is typically used for the treatment of seizure disorders and neuropathic pain. One of the major problems with this drug is its low solubility in water; therefore the objective of this study was to enhance the solubility of carbamazepine by complexation with cyclodextrin to be formulated as effervescent and dispersible granules.Methods: Solvent evaporation method was used to prepare, binary (Carbamazepine/β-cyclodextrin) complex and ternary (Carbamazepine/β-cyclodextrin/hydroxypropyl methyl cellulose (HPMC E5). The more soluble complex will be further formulated as unit dose effervescent and dispersible granules. The complexes were evaluated for their solubility, drug content, percentage practical yield and
... Show MoreQuercetin, one of the flavonoids family member, can be found in many vegetables, fruits, and beverages with a noticeable nutritional pharmacological properties. This study was aimed to evaluate the ability of quercetin to inhibit lipopolysaccharide (LPS) that induced lethal toxicity in vivo, and to elucidate the importance of the quercetin as an antitumor agent in breast cancer cell line MCF-7.In vivo experiments included the effect of hesperidin and LPS on the liver and spleen of male mice. In the liver, the antioxidant activity was measured by estimating the concentration of glutathione (GSH), and catalase (CAT), while in the spleen, the concentration of cytokines was measured including IL-33 and TNF-α. In vitro experiments included MTT
... Show MoreInterleukins (IL-2 and IL-4) are increased in asthmatics and were reported to induce resistance to steroid therapy in some patients who fail to get benefit from glucocorticoids when used in full dose and for long period of time. In this context, the present study was conducted on Iraqi patients to provide additional laboratory mean, beside the clinical diagnosis, for the decision whether the asthma is steroid sensitive or resistant by monitoring the level of immunoglobulins, complement proteins and interleukins among asthmatic patients (steroid sensitive or resistant) and the possible contribution of other factors like age, sex and environments in the development of steroid resistance. A total number of 55 asthmatics and 28 normal subjec
... Show MoreThe Back-Propagation (BP) is the best known and widely used learning algorithm in training multiple neural network. A vast variety of improvements to BP algorithm have been proposed since ninety’s. in this paper, the effects of changing the number of hidden neurons and activation equation are investigated. According to the simulation results, the convergence speed have been improved and become much faster by the previous two modifications on the BP algorithm.
The relationship between blood group antigens and peptic ulcer disease has been widely evaluated in the past, but only one study relating H pylori seroprevalence to ABO blood groups among Iraqi patients with peptic ulcer disease is available. We aimed to evaluate the frequency of peptic ulcer disease among different ABO blood groups in Iraqi patients, and we thought it was worthwhile to try to determine whether these components take some part in disease etiology. One hundred and six patients with peptic ulcer disease (PUD) (43 male and 63 female; mean age: 48 ± 18 years) who attended Baghdad teaching hospital and Al- Yarmouk teaching hospital endoscopy centers were enrolled , and 238 control Subjects. Fing
... Show MoreThe objective of the present investigation was to enhance the solubility of practically insoluble mirtazapine by preparing nanosuspension, prepared by using solvent anti solvent technology. Mirtazapine is practically insoluble in water which act as antidepressant .It was prepared as nano particles in order to improve its solubility and dissolution rate. Twenty formulas were prepared and different stabilizing agents were used with different concentrations such as poly vinyl pyrrolidone (PVPK-90), poly vinyl alcohol (PVA), poloxamer 188 and poloxamer 407. The ratios of drug to stabilizers used to prepare the nanoparticles were 1: 1 and 1:2. The prepared nanoparticles were evaluated for
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