Search results for "Polycyclic Compounds"
showing 10 items of 373 documents
Insulin Dissociates the Effects of Liver X Receptor on Lipogenesis, Endoplasmic Reticulum Stress, and Inflammation
2016
IF 4.258; International audience; Diabetes is characterized by increased lipogenesis as well as increased endoplasmic reticulum (ER) stress and inflammation. The nuclear hormone receptor liver X receptor (LXR) is induced by insulin and is a key regulator of lipid metabolism. It promotes lipogenesis and cholesterol efflux, but suppresses endoplasmic reticulum stress and inflammation. The goal of these studies was to dissect the effects of insulin on LXR action. We used antisense oligonucleotides to knock down Lxr alpha in mice with hepatocytespecific deletion of the insulin receptor and their controls. We found, surprisingly, that knock-out of the insulin receptor and knockdown of Lxr alpha …
The Vitamin D Receptor Regulates Glycerolipid and Phospholipid Metabolism in Human Hepatocytes.
2020
The vitamin D receptor (VDR) must be relevant to liver lipid metabolism because VDR deficient mice are protected from hepatosteatosis. Therefore, our objective was to define the role of VDR on the overall lipid metabolism in human hepatocytes. We developed an adenoviral vector for human VDR and performed transcriptomic and metabolomic analyses of cultured human hepatocytes upon VDR activation by vitamin D (VitD). Twenty percent of the VDR responsive genes were related to lipid metabolism, including MOGAT1, LPGAT1, AGPAT2, and DGAT1 (glycerolipid metabolism)
Liver X Receptor–Mediated Induction of Cholesteryl Ester Transfer Protein Expression Is Selectively Impaired in Inflammatory Macrophages
2009
Objective— Cholesteryl ester transfer protein (CETP) is a target gene for the liver X receptor (LXR). The aim of this study was to further explore this regulation in the monocyte-macrophage lineage and its modulation by lipid loading and inflammation, which are key steps in the process of atherogenesis. Methods and Results— Exposure of bone marrow–derived macrophages from human CETP transgenic mice to the T0901317 LXR agonist increased CETP, PLTP, and ABCA1 mRNA levels. T0901317 also markedly increased CETP mRNA levels and CETP production in human differentiated macrophages, whereas it had no effect on CETP expression in human peripheral blood monocytes. In inflammatory mouse and human mac…
High susceptibility of MDR and XDR Gram-negative pathogens to biphenyl-diacetylene-based difluoromethyl-allo-threonyl-hydroxamate LpxC inhibitors
2016
International audience; Inhibitors of uridine diphosphate-3-O-(R-3-hydroxymyristoyl)-N-acetylglucosamine deacetylase (LpxC, which catalyses the first, irreversible step in lipid A biosynthesis) are a promising new class of antibiotics against Gram-negative bacteria. The objectives of the present study were to: (i) compare the antibiotic activities of three LpxC inhibitors (LPC-058, LPC-011 and LPC-087) and the reference inhibitor CHIR-090 against Gram-negative bacilli (including MDR and XDR isolates); and (ii) investigate the effect of combining these inhibitors with conventional antibiotics.MethodsMICs were determined for 369 clinical isolates (234 Enterobacteriaceae and 135 non-fermentati…
OXA-163-Producing Klebsiella pneumoniae in Cairo, Egypt, in 2009 and 2010
2012
ABSTRACT Two genetically unrelated OXA-163-carrying Klebsiella pneumoniae strains were identified from two infection cases in June 2009 and May 2010 in Cairo, Egypt. OXA-163-producing Enterobacteriaceae had been previously reported in Argentina only. Both patients had no history of travel abroad. The emergence of this newly recognized OXA-48-related β-lactamase able to hydrolyze cephalosporins and carbapenems is especially worrying in a geographic area where OXA-48 is endemic and effective surveillance for antibiotic resistance is largely unaffordable.
Ovine corticotropin-releasing factor and dexamethasone responses in hyperandrogenic women
1990
Eighteen hyperandrogenic, hirsute women received ovine corticotropin-releasing factor (CRF; 1 microgram/kg) as well as a dexamethasone (DEX) suppression test. Nine of the 18 hirsute women exhibited increased DEX sensitivity. Plasma adrenocorticotropic hormone (ACTH) responses after ovine CRF were significantly lower in the DEX-sensitive subgroup, but serum androstenedione was higher. Baseline serum androgen levels could not predict DEX responses. A significant negative correlation existed between the suppression of androgens after DEX and the increase in ACTH after ovine CRF. The suppression of androgen correlated with the ratio of the increase in androgen to the increase in ACTH after ovin…
THE VITAMIN D RECEPTOR TAQ I POLYMORPHISM IS ASSOCIATED WITH REDUCED VDR AND INCREASED PDIA3 PROTEIN LEVELS IN HUMAN INTESTINAL FIBROBLASTS
2020
The synonymous single nucleotide polymorphism (SNP) rs731236, located in the vitamin D receptor (VDR) gene (Taq I) has been associated with both decreased levels of the protein in peripheral blood mononuclear cells and a fibrosis-related complication in Crohn´s disease (CD). Interactions between VDR and a protein-disulfide isomerase-associated 3 (PDIA3) in the regulation of extracellular matrix have been reported and we aim to analyze the relevance of the VDR genotypes and the effects of Vitamin D (VD) in the expression of VDR, PDIA3 and proliferation of intestinal fibroblasts. Human intestinal fibroblasts were isolated from the non-affected surgical resections of colorectal patients and cl…
Doxepin and its metabolites in plasma and cerebrospinal fluid in depressed patients
1997
Little information exists on the concentrations of antidepressants and their metabolites in CSF. We measured plasma and CSF levels of trans-doxepin (trans-DOX) and DOX metabolites in 12 depressed patients treated with DOX (250 mg/day) for 6 days. Spinal taps and blood samples were taken on day 7, 10 h after drug administration. Trans-DOX, cis-desmethyldoxepin (cis-DM-DOX), trans-desmethyldoxepin (trans-DM-DOX) and di-desmethyldoxepin (DDM-DOX) were analyzed in CSF and plasma samples by HPLC with column-switching. Although DOX was given as a mixture of 85% trans-DOX and 15% of the pharmacologically more active cis-DOX, we found similar amounts of cis-DM-DOX and trans-DM-DOX in plasma (59.8 +…
Tap water consumers differ from non-consumers in chlorine flavor acceptability but not sensitivity
2010
International audience; Unpleasant taste and especially chlorine flavor is one of the most common reasons advocated for choosing tap water alternatives as drinking water. As a consequence, the putative link between sensitivity to chlorine flavor and tap water consumption is an issue in drinking water habits studies. In the present study, we set out to examine such a link following a strategy in which we measured chlorine flavor perception at threshold and supra-threshold level for two groups of participants selected on their drinking water consumption habits. The first group included exclusive tap water consumers and the second group included exclusive bottled water consumers. In a first ex…
Disinfection by-products effect on swimmers oxidative stress and respiratory damage.
2015
Disinfection by-products (DBPs) are generated through the reaction of chlorine with organic and inorganic matter in indoor swimming pools. Different DBPs are present in indoor swimming pools. This study evaluated the effects of different chlorinated formations in oxidative stress and lung damage in 20 swimmers after 40 min of aerobic swimming in 3 indoor pools with different characteristics. Biological samples were collected to measure lung damage (serum-surfactant-associated proteins A and B), oxidative stress parameters (plasma protein carbonylation and malondialdehyde, and whole-blood glutathione oxidation), and swimming exertion values (blood lactate) before and after exercise. Free chl…