Search results for "Cysteine"
showing 10 items of 550 documents
Analysis of polymorphisms Leiden Factor V G1691A and prothrombin G20210A as risk factors for acute myocardial infarction.
2011
Thrombotic risk increases in elderly, therefore, the understanding of the genetic predisposition of hypercoagulability could make the difference in the prevention of venous and/or arterial thrombotic events. Laboratory evaluation of hyperfibrinogenemia, increased Factor VII levels, antiphospholipid antibodies presence and hyperhomocysteinemia are considered to have a consistent high predictivity for arterial thrombophilic diseases. Anyway, a large debate exists on the validity of testing Leiden Factor V (FV) G1691A and/or prothrombin (FII) G20210A polymorphisms in patients affected by arterial thrombotic diseases, despite of the several observations described. Here we report data strongly s…
Fluorovinylsulfones and -Sulfonates as Potent Covalent Reversible Inhibitors of the Trypanosomal Cysteine Protease Rhodesain: Structure–Activity Rela…
2021
Rhodesain is a major cysteine protease of Trypanosoma brucei rhodesiense, a pathogen causing Human African Trypanosomiasis, and a validated drug target. Recently, we reported the development of α-halovinylsulfones as a new class of covalent reversible cysteine protease inhibitors. Here, α-fluorovinylsulfones/-sulfonates were optimized for rhodesain based on molecular modeling approaches. 2d, the most potent and selective inhibitor in the series, shows a single-digit nanomolar affinity and high selectivity toward mammalian cathepsins B and L. Enzymatic dilution assays and MS experiments indicate that 2d is a slow-tight binder (Ki = 3 nM). Furthermore, the nonfluorinated 2d-(H) shows favorabl…
Distribution and differential induction of CYP2E1 by ethanol and acetone in the mesocorticolimbic system of rat
2008
Aims: The expression of cytochrome P4502E1 (CYP2E1) in the brain has been demonstrated in several regions, nevertheless there is a lack of specific studies on the constitutive expression and induction at the mesocorticolimbic system, the most relevant brain pathway in the context of drug addiction and alcoholism. Hence, we have performed a detailed study of the CYP2E1 expression and induction in three key areas of the mesocorticolimbic system of the rat brain: prefrontal cortex (PFC), nucleus accumbens (NAc), and ventral tegmental area (VTA). Methods: Expression levels of CYP2E1 were analyzed by Western blot. The induction of the enzyme in the selected brain areas by chronic acetone (1% v/v…
High frequency of functionally active Melan-a-specific T cells in a patient with progressive immunoproteasome-deficient melanoma.
2004
AbstractTumor-reactive T cells play an important role in cancer immunosurveillance. Applying the multimer technology, we report here an unexpected high frequency of Melan-A–specific CTLs in a melanoma patient with progressive lymph node metastases, consisting of 18 and 12.8% of total peripheral blood and tumor-infiltrating CD8+ T cells, respectively. Melan-A–specific CTLs revealed a high cytolytic activity against allogeneic Melan-A–expressing target cells but failed to kill the autologous tumor cells. Loading of the tumor cells with Melan-A peptide reversed the resistance to killing, suggesting impaired function of the MHC class I antigen processing and presentation pathway. Mutations of t…
Induction of hepatic heme oxygenase-1 by diclofenac in rodents: role of oxidative stress and cytochrome P-450 activity
2003
Abstract Background/Aims : The role of oxidative stress in diclofenac hepatotoxicity is still not clear. This study examined whether the drug induced heme oxygenase-1 (HO-1), a stress protein. Methods : HO-1 mRNA and HO activity were measured in mouse liver and in rat hepatocytes after treatment with diclofenac parallel to release of serum alanine aminotransferase (ALT) and sorbitol dehydrogenase (SDH) as a marker of hepatic damage. Results : HO-1 was transcriptionally and dose-dependently induced by diclofenac in mouse liver and rat hepatocytes. HO-1 mRNA, ALT and SDH peaked at the same time. Mechanistic studies revealed that the drug synergized with buthionine sulfoximine (BSO) in lowerin…
Evaluation of drug-metabolizing and functional competence of human hepatocytes incubated under hypothermia in different media for clinical infusion.
2008
Hepatocyte transplantation has been proposed as a method to support patients with liver insufficiency. Key factors for clinical cell transplantation to progress is to prevent hepatocyte damage, loss of viability and cell functionality, factors that depend on the nature of the tissue used for isolation to a large extent. The main sources of tissue for hepatocyte isolation are marginal livers that are unsuitable for transplantation, and segments from reduced cadaveric grafts. Hepatocellular transplantation requires infusing human hepatocytes in Suspension over a period of minutes to hours. The beneficial effect of hypothermic preservation of hepatocytes in infusion medium has been reported, b…
Oxidative stress triggers cytokinesis failure in hepatocytes upon isolation
2015
Primary hepatocytes are highly differentiated cells and proliferatively quiescent. However, the stress produced during liver digestion seems to activate cell cycle entry by proliferative/dedifferentiation programs that still remain unclear. The aim of this work was to assess whether the oxidative stress associated with hepatocyte isolation affects cell cycle and particularly cytokinesis, the final step of mitosis. Hepatocytes were isolated from C57BL/6 mice by collagenase perfusion in the absence and presence of N-acetyl cysteine (NAC). Polyploidy, cell cycle, and reactive oxygen species (ROS) were studied by flow cytometry (DNA, phospho-histone 3, and CellROX(®) Deep Red) and Western blott…
Computer-guided drug repurposing: Identification of trypanocidal activity of clofazimine, benidipine and saquinavir
2015
In spite of remarkable advances in the knowledge on Trypanosoma cruzi biology, no medications to treat Chagas disease have been approved in the last 40 years and almost 8 million people remain infected. Since the public sector and non-profit organizations play a significant role in the research efforts on Chagas disease, it is important to implement research strategies that promote translation of basic research into the clinical practice. Recent international public-private initiatives address the potential of drug repositioning (i.e. finding second or further medical uses for known-medications) which can substantially improve the success at clinical trials and the innovation in the pharmac…
Regulation of glutathione metabolism in Ehrlich ascites tumour cells.
1992
Glutathione metabolism was studied in cancer cells during the growth of an Ehrlich ascites tumour. GSH, but not GSSG, content decreases when cell proliferation and the rate of protein synthesis in the tumour decrease. This change correlates with a decrease in the rate of GSH synthesis and an increase in glutathione peroxidase and glutathione S-transferase activities. Glutathione efflux from tumour cells seems to co-ordinate with the rate of GSH synthesis. Cysteine, and not methionine, promotes GSH synthesis in tumour cells. However, changes in the rate of GSH synthesis are not due to limitations in the supply of blood cysteine or to changes in the intracellular amino acid pool of the cancer…
Association of ocular, cardiovascular, morphometric and lifestyle parameters with retinal nerve fibre layer thickness.
2017
BACKGROUND Glaucoma is a neurodegenerative disease, leading to thinning of the retinal nerve fibre layer (RNFL). The exact influence of ocular, cardiovascular, morphometric, lifestyle and cognitive factors on RNFL thickness (RNFLT) is unknown and was analysed in a subgroup of the Gutenberg Health Study (GHS). METHODS Global peripapillary RNFLT was measured in 3224 eyes of 1973 subjects (49% female) using spectral-domain optical coherence tomography (SD-OCT). The association of age, sex, ocular, cardiovascular, morphometric, lifestyle and cognitive factors on RNFLT was analysed using Pearson correlation coefficient and fitting a linear mixed model. RESULTS In the univariable analysis highest…