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.
Abstract
Prescribing drugs to patients to treat ailments or reducing their morbidity may not be enough, even if the drugs were all indicated and in the right dose. Clinical pharmacists play a pivotal role in conducting information and instruction to patients and conveying feedback to treating physician when appropriate, and the final goal is in the interest of the patient. Identification and classification of drug related problems and discussing them with the health care providers. Prospective, interventional, clinical study for 180 hemodialysis patients, and was designed as two phases, an observational phase to identify drug related problems and classifying them according to the latest Pharmaceutical
... Show MoreAbstract Diabetic nephropathy (DN) is a prevalent chronic microvascular diabetic complication. As inflammation plays a vital role in the development and progress of DN the macrophages migration inhibitory factor (MIF), a proinflammatory multifunctional cytokine approved to play a critical function in inflammatory responses in various pathologic situations like DN. This study aimed To assess serum levels of MIF in a sample of Iraqi diabetic patients with nephropathy supporting its validity as a marker for predicting nephropathy in T2DM patients. In addition, to evaluate the nephroprotective effect of angiotensin-converting enzyme (ACE) inhibitors in terms of their influence on MIF levels. This is a case-control study involving ninety
... Show MoreThis study deals with the subject of violence, but from another perspective, it has not been emphasized in contemporary studies of violence in Arabic and raqi universities, which is the structural or institutional aspect of violence. Traditional studies have focused their analysis of violence on the direct side the violence, The other side of the violence is the hidden violence, which is characterized by a lack of clarity of the underlying factors and its effects are not arises, which makes it the most serious violence, which requires a deep research into the social, political, economic, cultural and psychological structure of society (individuals and institutions). This study was based on the theory of the Norwegian scientist (J
... Show MoreThe concept of TQM is based on one of the concepts that combine administrative and innovative methods. The aim of the research is to demonstrate the dimensions of TQM in enhancing the satisfaction of the taxpayers through a survey of a sample of officials in the General Authority for Taxation and 50 officials. In the collection of data and information, and the results were analyzed using the SPSS program to find the most important compounds and factors in he method of analysis.
The research problem was represented by the non-application of the General Authority for Taxation to the entrances and modern practices in the administrative work. The results of some of the complications that accompany the tax accounting process, which af
... Show MoreThis study aims to fabricate and assess the β-tricalcium phosphate (β-TCP) bioactive ceramic coat layer on bioinert ceramic zirconia implants through the direct laser melting technique by applying a long-pulsed Nd:YAG laser of 1064 nm. Surface morphologies, adherence, and structural change in the coatings were evaluated by optical microscopy, field emission scanning electron microscope, hardness, and x-ray diffractometer. The elastic modulus (EM) of the coating was also determined using the nanoindentation test. The quality of the coating was improved when the laser power was 90 W with a decrease in the scan speed to 4 mm s−1. The chemical composition of the coat was maintained after laser processing; also, the Energy Dispersive
... Show MoreIn present study 74 specimens of urine were collected from patients suffering from urinary tract infections.Fifty (67.56%) isolates were identified as Escherichia coli. 78% of isolates were identified as extendedspectrum beta lactamases (ESBL) producer. Antibiotic susceptibility t est was done and ceftazidime wasselected to complete this study by implying stress at sub-MIC on isolate harbor high number of resistancegenes (N11) and compared with sensitive isolate (S). Only four β-lactamase coding genes were detected;blaTEM, blaPER, blaVIM and blaCTX-M-2 and N11 had blaTEM, blaPER, and blaVIM. It was found that the resistantisolate did not form biofilm when compared with the sensitive one, which formed moderate biofilm. Inaddition, ceftazidi
... Show MoreBackground: Gotu Kola (Centella asiatica) has been used as a traditional medicine for many years to cure different kinds of diseases. Studies have been reported that Gotu Kola extracts might be used as a cure for oral diseases such as periodontal disease. In the present study, Gotu Kola leaves extracted with water will be used to evaluate its effect on some microorganisms living in the human saliva using minimum inhibitory concentration (MIC) method. Material and Method:Gotu Kola fresh leaves extract have been used with water as a solvent, a rotary evaporator was used to separate the solvent from the extract. The following microorganisms: Streptococci, Lactobacilli, and Staphylococcus aureus have been isolated fromthe Saliva of ten voluntee
... Show MoreVerbs are an important material in the construction of the sentence, as they are among the requirements of every sophisticated language, and in this regard, Ibn Al-Gothic (d. 367 AH): “Know that verbs are the origins of the buildings of most speech, and thus scholars called them buildings.” Verbs are the source of expression of the speakers’ ideas to represent the element of activity and movement, and with their knowledge We infer the meanings of Arabic words, and Ibn Al-Sarraj (d. 316 AH) defined it: “The verb denotes a meaning and a time, and that time is either past, present, or future.” Its letters are original and does not drop from its construction a letter in the conjugation of its conjugations, and it is in Arabic two type
... Show MoreThe current study aimed to identify the difficulties faced by the student in mathematics and possible proposals to address these difficulties. The study used a descriptive method also used the questionnaire to collect data and information were applied to a sample of (163) male and female teachers. The results of the study found that the degree of difficulties in learning mathematics for the fifth and sixth grades is high for some paragraphs and intermediate for other paragraphs, included the student's field. The results also revealed that there were no statistically significant differences at the level of significance (α = 0.05) between the responses of the members of the study sample from male and female teachers to the degree of diffi
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