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showing 10 items of 10618 documents
Adaptation of neuronal cells to chronic oxidative stress is associated with altered cholesterol and sphingolipid homeostasis and lysosomal function
2009
Chronic oxidative stress has been causally linked to several neurodegenerative disorders. As sensitivity for oxidative stress greatly differs between brain regions and neuronal cell types, specific cellular mechanisms of adaptation to chronic oxidative stress should exist. Our objective was to identify molecular mechanisms of adaptation of neuronal cells after applying chronic sublethal oxidative stress. We demonstrate that cells resistant to oxidative stress exhibit altered cholesterol and sphingomyelin metabolisms. Stress-resistant cells showed reduced levels of molecules involved in cholesterol trafficking and intracellular accumulation of cholesterol, cholesterol precursors, and metabol…
Hyperglycemia and oxidative stress in cultured endothelial cells – a comparison of primary endothelial cells with an immortalized endothelial cell li…
2012
Diabetes mellitus is a major risk factor for the development of cardiovascular disease and oxidative stress plays an important role in this process. Therefore, we investigated the effects of hyperglycemia on the formation of reactive oxygen species (ROS) and nitric oxide/cGMP signaling in two different endothelial cell cultures. Human umbilical vein endothelial cells (HUVEC) and EA.hy 926 cells showed increased oxidative stress and impaired NO-cGMP signaling in response to hyperglycemia. The major difference between the two different cell types was the dramatic decrease in viability in HUVEC whereas EA.hy cells showed rather increased growth under hyperglycemic conditions. Starvation led to…
Pigmented esthesioneuroblastoma showing dual differentiation following transplantation in nude mice
1989
Esthesioneuroblastoma (ESTH) is a neuroepithelial-cell-derived neoplasm of the olfactory mucosa composed of homogeneous small round cells which contain neurosecretory granules. Melanin has been detected in such tumours only occasionally. Here we describe a new case of ESTH with divergent differentiation. The primary neoplasm was found in a 67 year-old female, involving the left nasal and maxillary sinus; she died of cerebral metastasis ten months after diagnosis. Histologically only small round cells were seen, with S-100 and NSE positivity. Electron microscopy revealed neurosecretory granules and filaments, as well as the occasional presence of melanosomes. A nude mice xenograft line has b…
Aging and systemic hormonal status affects the circulating miR-21, miR-146a and FasL levels
2015
MicroRNAs are small molecules, found in all cell types and body fluids, which most commonly affect negatively to gene expressions by translational repression. Their role in various physiological conditions and diseases has been emphasized during the last twenty years. In our recent studies with postmenopausal monozygotic twin sisters (n=11), we have investigated how different systemic hormonal status affects the levels of specific circulating microRNAs and other molecules related to inflammation and apoptosis, both processes associated with aging. Our results have shown that the systemic levels of miR-21, miR-146a and Fas ligand are lower within the postmenopausal women who are using estrog…
Physical activity responsive miRNAs – Potential mediators of training responses in human skeletal muscle?
2013
1. The basics of miRNA-mediated regulation The plasticity of skeletal muscle is of utmost importance for responding to and coping with environmental demands that emerge from changes in physical activity patterns, nourishment, hormonal status, and health. As is well known, a sedentary lifestyle, aging, immobilization, and chronic diseases are associated with reduced muscle mass and function, while regular exercise improves muscle function and reduces the rate of decrement throughout life. 1 However, we do not have a complete understanding of the molecular factors controlling skeletal muscle adaptation to exercise stimuli. Recently identified microRNA molecules (miRNAs) have rapidly gained at…
Intermittent ethanol exposure induces inflammatory brain damage and causes long-term behavioural alterations in adolescent rats
2007
Adolescent brain development seems to be important for the maturation of brain structures and behaviour. Intermittent binge ethanol drinking is common among adolescents, and this type of drinking can induce brain damage. Because we have demonstrated that chronic ethanol treatment induces inflammatory processes in the brain, we investigate whether intermittent ethanol intoxication enhances cyclooxygenase-2 (COX-2) and inducible nitric oxide synthase (iNOS) in adolescent rats, and whether these mediators induce brain damage and cause permanent cognitive dysfunctions. Adolescent rats were exposed to ethanol (3.0 g/kg) for two consecutive days at 48-h intervals over 14 days. Levels of COX-2, iN…
The Dual Role of the GABAA Receptor in Peripheral Inflammation and Neuroinflammation: A Study in Hyperammonemic Rats
2021
Cognitive and motor impairment in minimal hepatic encephalopathy (MHE) are mediated by neuroinflammation, which is induced by hyperammonemia and peripheral inflammation. GABAergic neurotransmission in the cerebellum is altered in rats with chronic hyperammonemia. The mechanisms by which hyperammonemia induces neuroinflammation remain unknown. We hypothesized that GABAA receptors can modulate cerebellar neuroinflammation. The GABAA antagonist bicuculline was administrated daily (i.p.) for four weeks in control and hyperammonemic rats. Its effects on peripheral inflammation and on neuroinflammation as well as glutamate and GABA neurotransmission in the cerebellum were assessed. In hyperammone…
Should we measure routinely oxidised and atherogenic dense low-density lipoproteins in subjects with type 2 diabetes?
2010
Beyond low-density lipoprotein (LDL)-cholesterol concentrations, in recent years, several clinical studies have shown that both oxidised and small, dense LDL have a strong predictive role for the presence of vascular atherosclerosis. These two lipid parameters seem to have a synergistic impact on cardiovascular risk, with a greater importance in patients at higher-risk, such as those with type-2 diabetes. Increased levels of oxidised and small, dense LDL levels are a feature of diabetic dyslipidaemia, and small, dense LDL have been shown to be a good predictor of future cardiovascular events, at both univariate and multivariate analyses. On the other hand, although the association of oxidis…
A young patient with type 2 diabetes associated non-alcoholic steatohepatitis, liver cirrhosis, and hepatocellular carcinoma.
2020
The rising prevalence of the metabolic syndrome has led to an increase of non-alcoholic fatty liver disease (NAFLD), and its progressive-inflammatory form called non-alcoholic steatohepatitis (NASH). In recent years, NAFLD and NASH have become major risk factors for developing liver cirrhosis and hepatocellular carcinoma (HCC). In this case, we report a 46-year-old patient with type 2 diabetes mellitus and metabolic comorbidities including obesity and arterial hypertension, who was referred because of rising liver enzymes. After clinical and diagnostic evaluation, the patient was diagnosed with NASH-associated liver cirrhosis, Child-Pugh stage B. A normal blood sugar level was difficult to …
Cost Effectiveness of Peginterferon ??-2a Plus Ribavirin versus Interferon ??-2b Plus Ribavirin as Initial Therapy for Treatment-Naive Chronic Hepati…
2004
Introduction: In adults with previously untreated chronic hepatitis C (CHC), the combination of peginterferon α-2a plus ribavirin produces a higher rate of sustained virological response (SVR) than interferon α-2b plus ribavirin, but it is still unproven whether this increase is cost effective. The objective of this study was to determine if the gain in SVR with peginterferon α-2a plus ribavirin is worth the incremental cost. Methods: We constructed a Markov model of disease progression in which cohorts of patients received peginterferon α-2a plus ribavirin or interferon α-2b plus ribavirin for 48 weeks (hepatitis C virus [HCV] genotype 1 and non-1 patients with fibrosis) or 24 weeks (genot…