1,721,071 research outputs found
Telomeres and atherosclerosis
No full textAbstract The pathogenesis of atherosclerosis, an age-related disorder, may be due to a premature
biological ageing. Cellular senescence, the finite replicative lifespan of cells, plays a critical
role in the pathogenesis of atherosclerosis. The biological mechanism that triggers the onset of
cellular senescence is thought to be telomere shortening. The two major mechanisms responsible
for telomere shortening are the end-replication problem, oxidative DNA damage as well
as inflammation induced by environmental risk factors. Repair of the endothelium depends on
the presence of endothelial progenitor cells which depends on the hematopoietic stem cells
(HSC) reserves. In numerous past studies, short LTL has been associated with atherosclerosis.
Here we review the literature on telomere biology and coronary artery disease (CAD)
Telomere shortening as genetic risk factor of liver cirrhosis
No full textCirrhosis is the main complication of chronic liver disease, leads to progressive liver function impairment and is the main risk factor for the development of liver cancer. Liver failure at endstage cirrhosis is associated with increased mortality with liver transplantation as the only possible treatment at this stage. The pathogenesis of liver cirrhosis is not completely elucidated. Although the common factors leading to liver injury, such as viral hepatitis, alcohol consume or fatty liver disease can be identified in the majority of patients a small percentage of patients have no apparent risk factors. Moreover given the same risk factors, some patients progress to cirrhosis whereas others have a benign course, the reason remains unclear. In order to develop new diagnostic and therapeutic tools, it is s essential to understand the pathogenesis of cirrhosis. The identification of genetic risk factors associated with cirrhosis is one of the possible approach to achieve these goal. In the past years several studies have supported the role of telomere shortening and cirrhosis. In the recent year several studies on the relation between several single nucleotide polymorphism (SNPs) and cirrhosis have been published; it has been proposed also a cirrhosis risk score based on seven SNPs. Also epidemiological studies on identical twins and in different ethnic groups have been supporting the importance of the role of genetic risk factors. Finally in the very recent years it has been suggested that telomere shortening may represent a genetic risk factor for the development of cirrhosis
Telomere and telomerase in chronic liver disease and hepatocarcinoma
No full textThe pathogenesis of liver cirrhosis is not completely elucidated. Although in the majority of patients, the risk factors may be identified in B and C viral hepatitis, alcohol intake, drugs or fatty liver disease, there is a small percentage of patients with no apparent risk factors. In addition, the evolution of chronic liver disease is highly heterogeneous from one patient to another. Among patient with identical risk factors, some rapidly progress to cirrhosis and hepatocellular carcinoma (HCC) whereas others have a benign course. Therefore, a genetic predisposition may contribute to the development of cirrhosis and HCC. Evidence supporting the role of genetic factors as a risk for cirrhosis has been accumulating during the past years. In addition to the results from epidemiological studies, polymorphisms studies and data on twins, the concept of telomere shortening as a genetic risk factor for chronic liver disease and HCC has been proposed. Here we review the literature on telomerase mutations, telomere shortening and liver disease including hepatocellular carcinoma
Interethnic diffrences in Free Fatty acids and glucose metabolism in asian Indians and Caucasinas
No full textMild increase in body fat content is known to induce excessive insulin resistance in Asian Indians compared to Caucasians. We evaluated the difference in Free fatty acids and Glucose metabolism in Asian Indians and Caucasians. Insulin-dependent plasma FFA suppression is impaired in Asian Indians with even minor body fat content compared to Caucasians. Furthermore , induced plasma FFA elevation had much more impact on insulinmediated glucose disposal of Asian Indians than Caucasians even in very thin and insulin sensitive subjetcs
Olanzapine-induced hypertriglyceridemia and Diabetes mellitus
No full textBackgroundHypertriglyceridemia (HTG), weight gain and new onset diabetes mellitus (DM) are documented side effects of olanzapine (OLZ). Case reports of OLZ-induced ketoacidosis with DM has been recently described. Weight gain often does not correlate with the severity of HTG and/or DM observed and it is difficult to delineate the direct effects of OLZ versus those associated with OLZ–induced obesity.We report a case showing improvement of lipid and glucose metabolism after discontinuation of OLZ, independent of body weight.Case recordA 36 years old white man had a 5 years history of hospitalizations for schizophrenia, with unremarkable lipid and glucose profile prior to initiation OLZ in October 2006. He had weight 90 Kg and BMI 33 Kg/m2. He initiated OLZ and started losing weight, with polydipsia and polyuria; in February 2007 a blood test disclosed HTG (1151 mg/dl), hyperglycemia (463 mg/dl), glycosuria (8902 mg/dl) and ketonuria (80 mg/dl). A subsequent blood test upon hospital admission showed TG=3298 mg/dl, glycated haemoglobin A1C=14.3%. His body weight was 76 Kg, BMI 27 Kg/m2 and waist circumference 90 cm. Serum insulin, serum and urinary C peptide, serum amylases and lipases and abdomen CT scan did not show any alteration.OLZ was discontinued and the patient put on insulin therapy and hydration. After one week we observed a complete remission of HTG (176 mg/dl) and improvement of glucose metabolism (glycaemia=249 mg/dl, glycosuria=652 mg/dl). A month after discharge, he still presented hyperglycaemia.ConclusionOur case demonstrates changes in OLZ-related HTG and DM unrelated to weight gain. The patient had no other cause of HTG so OLZ appeared to have a direct effect on lipid metabolism independently of weight gain. He had a family history of DM and it’s possible that the OLZ acted on a DM susceptibility. Future research is needed in order to understand the mechanisms related to glucose and lipid metabolism of atypical antipsychotic drugs
The genetic basis of Insulin resistance. A brief review
No full textInsulin resistance, represents the primary physiologic defect underlying the metabolic syndrome (MS) which includes insulin resistance/hyperinsulinemia, glucose intolerance and/or type 2 diabetes mellitus, visceral obesity, hypertension, and dyslipidemia. This constellation of traits is a major risk factor of cardiovascular mortality and morbidity. Insulin sensitivity varies among individuals. Although environment, physical inactivity and caloric excess, plays an important role in the development of obesity and thus insulin resistance, several studies show that there are also a genetic influence in the development of insulin resistance. Extreme forms of insulin resistance may be caused by mutations in the genes for the insulin receptor and peroxisome proliferator-activated receptor gamma, these forms rare. The genetic basis for common more moderate forms of insulin resistance is likely to be polygenic and heterogeneous. There is evidence that gene variants may have phenotypic influences on more than one MS traits which may explain, in part, the clustering of these traits. We briefly review in this article the evidence that insulin resistance has a genetic basis. The identification of specific gene variants will help understanding the molecular basis of MS and ultimately will help to set up preventive and therapeutic interventio
Endocrine and liver interaction: the role of endocrine pathways in NASH
No full textThis article reviews evidence that causally links hormonal disorders with hepatobiliary disease, and gives particular focus to nonalcoholic steatohepatitis (NASH). The downstream mechanisms by which endocrine disturbances cause liver disease might be similar to those involved in the development of primary liver disease. Hypothyroidism, for example, might lead to NASH, cirrhosis and potentially liver cancer via the development of hyperlipidemia and obesity. Patients with growth hormone deficiency have a metabolic-syndrome-like phenotype that is also associated with the development of NASH. Polycystic ovary syndrome is a common endocrine disorder that is often associated with insulin resistance, the metabolic syndrome, altered levels of liver enzymes and the development of NASH. Recent findings support a role of dehydroepiandrosterone sulfate deficiency in the development of advanced NASH. In addition, adrenal failure is increasingly reported in patients with end stage liver disease and in patients who have received a liver transplant, which suggests a bidirectional relationship between liver and endocrine functions. Clinicians should, therefore, be aware of the potential role of endocrine disorders in patients with cryptogenic liver disease and of the effects of liver function on the endocrine system
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