Search results for "Reductase"

Chronic kidney disease and dyslipidaemia

2016

Chronic kidney disease (CKD) has to be considered as a high, or even very high risk cardiovascular risk condition, since it leads to an increase in cardiovascular mortality that continues to increase as the disease progresses. An early diagnosis of CKD is required, together with an adequate identification of the risk factors, in order to slow down its progression to more severe states, prevent complications, and to delay, whenever possible, the need for renal replacement therapy. Dyslipidaemia is a factor of the progression of CKD that increases the risk in developing atherosclerosis and its complications. Its proper control contributes to reducing the elevated cardiovascular morbidity and …

Androgen metabolism in the skin of the rainbow trout (Oncorhynchus mykiss)

1993

Pieces of skin of male and female rainbow trout (Oncorhynchus mykiss) were incubated with testosterone and 11-ketotestosterone as substrates. In immature fish the conversion rate was low. In non-spawning adult males 11-ketotestosterone was reduced to 5α-11KDHT (up to 5.2%). In the fish in spawning condition the 5α-reduction rate was only about 1 to 2%. In the same specimens incubated with testosterone a high 11β-hydroxylase activity (23.8-25% in the male and 13% in the female skin) was found. Similar sex specific differences were observed for the occurence of 5α-reduced metabolites (about 20% in the male and 13% in the female tissue).

Case-specific performance of MM-PBSA, MM-GBSA, and SIE in virtual screening.

2015

In drug discovery the reliable prediction of binding free energies is of crucial importance. Methods that combine molecular mechanics force fields with continuum solvent models have become popular because of their high accuracy and relatively good computational efficiency. In this research we studied the performance of molecular mechanics generalized Born surface area (MM-GBSA), molecular mechanics Poisson-Boltzmann surface area (MM-PBSA), and solvated interaction energy (SIE) both in their virtual screening efficiency and their ability to predict experimentally determined binding affinities for five different protein targets. The protein-ligand complexes were derived with two different app…

Inhibition of xanthine oxidase to prevent statin-induced myalgia and rhabdomiolysis

2015

Although statins remain the cornerstone of lipid-lowering therapy for reducing the burden of atherosclerotic vascular disease, their administration has been associated with muscle-related adverse effects, including myalgia and rhabdomyolysis. Such adverse events are probably due to reduced antioxidant defenses associated with fewer intermediate metabolites in the cholesterol synthesis pathway. We hypothesize that the concomitant inhibition of xanthine oxidase via coadministration of allopurinol with statins could diminish reactive oxygen species (ROS)-related muscle damage, which would have in turn have positive effects on both the incidence of muscle-related adverse events and cardiovascul…

Management of Statin Intolerance in 2018: Still More Questions Than Answers.

2018

Statin therapy is generally well tolerated and very effective in the prevention and treatment of cardiovascular disease, regardless of cholesterol levels; however, it can be associated with various adverse events (myalgia, myopathy, rhabdomyolysis, and diabetes mellitus, among others). Patients frequently discontinue statin therapy without medical advice because of perceived side effects and consequently increase their risk for cardiovascular events. In patients with statin intolerance, it may be advisable to change the dose, switch to a different statin, or try an alternate-day regimen. If intolerance is associated with all statins—even at the lowest dose—non-statin drugs and certain nutra…

Analysis of vitamin D levels in patients with and without statin-associated myalgia — A systematic review and meta-analysis of 7 studies with 2420 pa…

2014

article i nfo Introduction: VitaminD (vitD)deficiencymay beassociatedwith anincreased riskof statin-related symptomatic myalgia in statin-treated patients. The aim of this meta-analysis was to substantiate the role of serum vitamin D levels in statin-associated myalgia. Methods: The search included PUBMED, Cochrane Library, Scopus, and EMBASE from January 1, 1987 to April 1, 2014 to identify studies that investigated the impact of vit D levels in statin-treated subjects with and without myalgia. Two independent reviewers extracted data on study characteristics, methods and outcomes. Quantita- tive data synthesis was performed using a fixed-effect model. Results: The electronic search yielde…

Comparison of oxidoreductive enzyme activities in three coal tar creosote-contaminated soils

2019

This study used laboratory experiments to compare the effects of coal tar creosote on the activity of oxidoreductive enzymes in sandy loam, loamy sand and sandy clay loam soils. Different amounts of coal tar creosote were added to soil samples as follows: 0 (control), 2, 10 or 50 g kg–1 dry matter. The activity of soil dehydrogenases (DHAs), o-diphenol oxidase (o-DPO), catalase (CAT), nitrate reductase (NR) and peroxidases (POX) was determined. Contamination of soil with coal tar creosote affected oxidoreductase activity. Oxidoreductive enzyme activity following soil contamination with coal tar creosote was in the following order: DHAs > CAT > NR > POX > o-DPO in…

Relative abundance of the membrane bound- and periplasmic nitrate-reductases in the environment

2007

Rac1-Regulated Endothelial Radiation Response Stimulates Extravasation and Metastasis That Can Be Blocked by HMG-CoA Reductase Inhibitors

2011

Radiotherapy (RT) plays a key role in cancer treatment. Although the benefit of ionizing radiation (IR) is well established, some findings raise the possibility that irradiation of the primary tumor not only triggers a killing response but also increases the metastatic potential of surviving tumor cells. Here we addressed the question of whether irradiation of normal cells outside of the primary tumor augments metastasis by stimulating the extravasation of circulating tumor cells. We show that IR exposure of human endothelial cells (EC), tumor cells (TC) or both increases TC-EC adhesion in vitro. IR-stimulated TC-EC adhesion was blocked by the HMG-CoA reductase inhibitor lovastatin. Glycyrr…

Aplidin® induces JNK-dependent apoptosis in human breast cancer cells via alteration of glutathione homeostasis, Rac1 GTPase activation, and MKP-1 ph…

2006

Aplidin® is an antitumor agent in phase II clinical trials that induces apoptosis through the sustained activation of Jun N-terminal kinase (JNK). We report that Aplidin® alters glutathione homeostasis increasing the ratio of oxidized to reduced forms (GSSG/GSH). Aplidin® generates reactive oxygen species and disrupts the mitochondrial membrane potential. Exogenous GSH inhibits these effects and also JNK activation and cell death. We found two mechanisms by which Aplidin® activates JNK: rapid activation of Rac1 small GTPase and downregulation of MKP-1 phosphatase. Rac1 activation was diminished by GSH and enhanced by L-buthionine (SR)-sulfoximine, which inhibits GSH synthesis. Downregulatio…