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.
Many pathophysiological processes can affect the pharmacokinetic properties of drugs in people with diabetes. The present study was deigned to evaluate the influence of diabetes mellitus (DM) on the pharmacokinetic parameters of metronidazole administered as single oral dose. Twelve healthy volunteers and twelve diabetic patients were enrolled in the present study. On day 1, a single oral dose of metronidazole 500 mg was administered orally to all participants at 9:00 am after a 10-hour fasting. Over the following 48 hours, blood samples were taken at frequent intervals and serum metronidazole concentrations were measured by a high-performance liquid chromatography method for assessment of pharmacokinetics of metronid
... Show MoreBackground: Multifactor affect the pathogenesis of thrombosis in solid malignancy; however, a significant role is attributed to the cancer cells ability to interact with and activate the host hemostatic system. [1]
Hemostasis is highly correlated to tumor growth, angiogenesis and metastasis, modulation of these pathways reflects interesting and promising treatment options in the future. [1]
Most patients with cancer frequently suffer from chronic compensated DIC and have abnormal laboratory coagulation tests without clinical manifestations of thrombosis, which is a subclinical hypercoagulable state that can be detected by varying degrees of activation of blood clotting. The results of laboratory tests in th
... Show MoreMany pathophysiological processes can affect the pharmacokinetic properties of drugs in people with diabetes. The present study was deigned to evaluate the influence of diabetes mellitus (DM) on the pharmacokinetic parameters of metronidazole administered as single oral dose. Twelve healthy volunteers and twelve diabetic patients were enrolled in the present study. On day 1, a single oral dose of metronidazole 500 mg was administered orally to all participants at 9:00 am after a 10-hour fasting. Over the following 48 hours, blood samples were taken at frequent intervals and serum metronidazole concentrations were measured by a high-performance liquid chromatography method for assessment of pharmacokinetics of metronidazole. The data
... Show Morevitrofertilization/intracytoplasmic sperm injection-embryo transfer (IVF/ICSI-ET) for infertile patients. Insulin like growth factor 1 (IGF1), Dehydroepiandrosterone sulfate (DHEAS) and Total Testosterone (TT) may have a role on follicle growth, oocyte quality, embryo quality and subsequent pregnancy in patients undergoing IVF cycles. To explore the possibility of using DHEAS, TT and IGF1 as predictive indicator for successful pregnancy in patients undergoing (IVF/ICSI-ET). A prospective study was performed enrolling (12) non pregnant control group,(7) pregnant control group,(18) non-pregnant PCOS group and (12) pregnant PCOS group. The collection of blood and follicular fluid (FF) samples was done at the day of oocyte aspiration. Electroch
... Show MoreThis research deals with one scene from the movie Romeo and Juliet, which is the balcony scene, due to the importance of this scene in the formation of the construction of the subsequent events of the movie.
The first chapter contained the methodological framework of the research, where the research problem was identified in how Zeffirelli dealt with the balcony scene in the play Romeo and Juliet and enriched it in the cinematic language with a comparison with the original text of the scene. In the balcony scene with comparative parts between the film and the text and the limits of the research that was limited to the film Zeffirelli and the translated text by Munis Taha Hussein.
The second chapter contained the theoretic
... Show MoreAn experiment was conducted to study the effect of the sprayer type according to the source of power and the size of the spray nozzle concerning the quality of the spray produced and fuel consumption.Two types of sprayers were used: a conventional boom sprayer (S1) and a modified (electrified) boom sprayer (S2), along with three sizes of the XR TeeJet 110 spray nozzle (N). The following technical performance indicators were examined: Density of coverage (drops/cm2) using ImageJ software, a 600dpi business card scanner, specifically the ScanShell 800N by CSSN, Inc, and water-sensitive paper (WSP), rate of spray nozzles discharge (ml/min), and fuel consumption (liters/hectare) using a c
This study research to Showing The impact of the integration process on the quality of Insurance service and analyze the impact financially to determine whether there is any impact on the quality of the insurance service, in addition to identifying the obstacles that impede the merger between the insurance companies, insurance and the appropriate proposals for its' application and benefit from the benefits achieved.
The importance of The study lies in the fact that it is an important and vital spotlight that is becoming increasingly important in the world to confront the various difficulties and crises that have occurred recently in light of the liberalization of international trade, globalization a
... Show MoreBackground: Adipose derived-mesenchymal stem cells have been used as an alternative to bone marrow cells in this study. Objective: We investigated the in vitro isolation, identification, and differentiation of stem cells into neuron cells, in order to produce neuron cells via cell culture, which would be useful in nerve injury treatment. Method: Mouse adipose mesenchymal stem cells were dissected from the abdominal subcutaneous region. Neural differentiation was induced using β-mercaptoethanol. This study included two different neural stage markers, i.e. nestin and neurofilament light-chain, to detect immature and mature neurons, respectively. Results: The immunocytochemistry results showed that the use of β-mercaptoethanol resulted in
... Show MoreBackground: Imaging techniques play a very important role in the specialty of endodontic. The ultrasonographic technique is non-expensive procedure, safe, and reproducible. The aim of the study was to determine the sensitivity, specificity, and accuracy of ultrasound and color Doppler ultrasonography in evaluation of periapical lesions (cyst, granuloma, mixed lesion “cyst within graulomas mass”, and abscess. Subject, Material and method: The sample consists of prospective study for 64 Iraqi participants who attended Karbalaa Specialized Center for Dentistry (males & females). Those patients were diagnosed clinically and radiographically as having periapical lesions of dental origin. They were examined by real time ultrasound and color
... Show More