Search results for "I-h"
showing 10 items of 184 documents
Compromising mitochondrial function with the antiretroviral drug efavirenz induces cell survival-promoting autophagy
2011
Hepatotoxicity is a very common side effect associated with the pharmacological treatment of human immunodeficiency virus (HIV) infection and its pathogenesis is poorly understood. Efavirenz (EFV) is the most widely used nonnucleoside reverse transcriptase inhibitor administered for the control of HIV and some of its toxic effects in hepatic cells have been recently shown to display features of mitochondrial dysfunction. Here we studied the activation of autophagy and, in particular, mitophagy, the main mitochondrial turnover mechanism, in human hepatic cells treated with clinically relevant concentrations of this drug. EFV-treated cells had altered mitochondria, characterized by a relative…
ER stress in human hepatic cells treated with Efavirenz: Mitochondria again
2013
Background & Aims ER stress is associated with a growing number of liver diseases, including drug-induced hepatotoxicity. The non-nucleoside analogue reverse transcriptase inhibitor Efavirenz, a cornerstone of the multidrug strategy employed to treat HIV1 infection, has been related to the development of various adverse events, including metabolic disturbances and hepatic toxicity, the mechanisms of which remain elusive. Recent evidence has pinpointed a specific mitochondrial effect of Efavirenz in human hepatic cells. This study assesses the induction of ER stress by Efavirenz in the same model and the implication of mitochondria in this process. Methods Primary human hepatocytes and Hep3B…
Inhibition of Mitochondrial Function by Efavirenz Increases Lipid Content in Hepatic Cells
2010
Efavirenz (EFV) is a non-nucleoside reverse transcriptase inhibitor (NNRTI) widely used in human immunodeficiency virus (HIV) infection therapy. It has been associated with hepatotoxic effects and alterations in lipid and body fat composition. Given the importance of the liver in lipid regulation, we have evaluated the effects of clinically used concentrations of EFV on the mitochondria and lipid metabolism of human hepatic cells in vitro. Mitochondrial function was rapidly undermined by EFV to an extent that varied with the concentration employed; in particular, respiration and intracellular adenosine triphosphate (ATP) levels were reduced whereas reactive oxygen species (ROS) production i…
Efavirenz induces interactions between leucocytes and endothelium through the activation of Mac-1 and gp150,95
2013
The potential cardiovascular (CV) toxicity associated with combined antiretroviral therapy (cART) has been attributed mainly to the nucleoside reverse transcriptase inhibitors abacavir and didanosine. However, the other two components of cART--non-nucleoside reverse transcriptase inhibitors (NNRTIs) and protease inhibitors (PIs)--may also be implicated, either directly or by influencing the action of the other drugs. This study evaluates the acute direct effects of the NNRTIs efavirenz and nevirapine and one of the most widely employed PIs, lopinavir, on leucocyte-endothelium interactions, a hallmark of CV disease.Drugs were analysed in vitro in human cells (interactions of peripheral blood…
Enhanced oxidative stress and increased mitochondrial mass during Efavirenz-induced apoptosis in human hepatic cells
2010
BACKGROUND AND PURPOSE Efavirenz (EFV) is widely used in the treatment of HIV-1 infection. Though highly efficient, there is growing concern about EFV-related side effects, the molecular basis of which remains elusive. EXPERIMENTAL APPROACH In vitro studies were performed to address the effect of clinically relevant concentrations of EFV (10, 25 and 50 mu M) on human hepatic cells. KEY RESULTS Cellular proliferation and viability were reduced in a concentration-dependent manner. Analyses of the cell cycle and several cell death parameters (chromatin condensation, phosphatidylserine exteriorization, mitochondrial proapoptotic protein translocation and caspase activation) revealed that EFV tr…
Pharmacokinetic interaction between efavirenz and ketoconazole in rats
2009
It is well known that efavirenz and ketoconazole act as an inducer and inhibitor of CYP3A4, respectively. As a result of these actions, co-administration of these drugs may result in changes in the pharmacoki- netic parameters of one or both of them. 2. Duodenum-cannulated rats have been used to compare the effect of intraduodenal (KC i.d. ) and intrave- nous administration of ketoconazole (KC i.v. ) on the pharmacokinetics of efavirenz after intraduodenal administration, as well as the potential effect of efavirenz as a CYP450 inducer on ketoconazole phar - macokinetic profile. 3. While KC i.v. did not show any significant effect on efavirenz pharmacokinetic profile, KC i.d. increased sig-…
Inhibition of Efavirenz Metabolism by Sertraline and Nortriptyline and Their Effect on Efavirenz Plasma Concentrations.
2015
ABSTRACT Between 22 and 45% of HIV-positive subjects are likely to report symptoms of depression. Considering this background, a potential pharmacokinetic interaction between the nonnucleoside reverse transcriptase inhibitor efavirenz (EFV) and two antidepressants, sertraline (SRT) and nortriptyline (NT), was studied. Rats were administered EFV alone or together with the antidepressants, and changes in the plasma levels and pharmacokinetic parameters of EFV were analyzed. Additional in vitro experiments with rat and human hepatic microsomes were carried out to evaluate the inhibitory effect of SRT and NT on EFV metabolism by determining the formation rate of the major EFV metabolite (8-OH-E…
Involvement of nitric oxide in the mitochondrial action of efavirenz: a differential effect on neurons and glial cells
2014
Abstract The anti-human immunodeficiency virus (HIV) drug efavirenz (EFV) alters mitochondrial function in cultured neurons and glial cells. Nitric oxide (NO) is a mediator of mitochondrial dysfunction associated with HIV central nervous system symptoms. We show that EFV promotes inducible nitric oxide synthase (iNOS) expression in cultured glial cells and generated NO undermines their mitochondrial function, as inhibition of NOS partially reverses this effect. EFV inhibits mitochondrial Complex I in both neurons and glia; however, when the latter cells are treated for longer periods, other mitochondrial complexes are also affected in accordance with the increased NO production. These findi…
Mobile Encounter Network - the missing data link
2008
In this paper, we discuss about the applicability of a short-range wireless communication scheme called Mobile Encounter Network (MEN). Encounters between devices communicating while moving allows ad-hoc -type data transfer to be performed. A background for the emerging of such networks is given. The essential properties of the MEN data transfer are specified. Based on this, the role of MEN as a data transfer medium is discussed. The conclusion is that such networking technique may provide additional value compared to the traditional wireless communication.
Skulls, Tree Bark, Fossils
2021
AbstractStudies of material objects in the field of memory studies have followed diverse epistemological and disciplinary trajectories, but their shared characteristic has been the questioning of philosophical assumptions concerning human relations with inanimate things and lower-level organic objects, such as plants, within the Aristotelian hierarchy of beings. Rather than accept at face value their categorizations as passive or deficient in comparison to the human subject, critical scholarship has reformulated the place and role of nonhuman entities in culture. This essay examines the nexus of materiality and memory in the work of the French philosopher and art historian Georges Didi-Hube…