losartan-potassium and Metabolic-Diseases

Cytokine and growth factor--erythropoietin (EPO)--apart from it's hematopoietic function is now considered to be a cytoprotective agent in a variety of vascular diseases, nervous system disorders and metabolic impairments. Recent work has elucidated that erythropoietin controls a variety of signal transduction pathways involving Janus-tyrosine kinase 2, protein kinase B, signal transducer and activator of transcription, Wnt proteins, forkhead transcription factors, caspases, and nuclear factor kappaB. Further investigations of cellular pathways controlled by erythropoietin can be the base for therapeutic applicability of this cytokine throughout the body.

Topics: Animals; Cytoprotection; Erythropoietin; Humans; Janus Kinase 2; Metabolic Diseases; Nervous System Diseases; Protein Binding; Proto-Oncogene Proteins c-akt; Signal Transduction; TYK2 Kinase; Vascular Diseases

Topics: Amino Acids; Bicarbonates; Dietary Proteins; Energy Metabolism; Erythropoietin; Exercise Therapy; Histocompatibility; Humans; Insulin-Like Growth Factor I; Kidney; Kidney Failure, Chronic; Malnutrition; Metabolic Diseases; Prenatal Nutritional Physiological Phenomena; Recombinant Proteins; Renal Dialysis

Topics: Allosteric Regulation; Animals; Carbon Dioxide; Chemical Phenomena; Chemistry; Diphosphoglyceric Acids; Erythrocytes; Erythropoiesis; Erythropoietin; Hemoglobins; Hemoglobins, Abnormal; Humans; Hydrogen-Ion Concentration; Kidney; Metabolic Diseases; Methemoglobin; Mutation; Oxygen; Protein Conformation

Topics: Anemia; Bone Marrow; Dextrans; Erythrocytes; Erythropoiesis; Erythropoietin; Ferritins; Hemosiderin; Histiocytes; Humans; Intestinal Absorption; Iron; Iron Radioisotopes; Kidney Failure, Chronic; Liver; Metabolic Diseases; Molecular Weight; Mononuclear Phagocyte System; Polycythemia; Spleen; Transferrin

Erythropoietin (EPO) has shown beneficial effects in the regulation of obesity and metabolic syndrome; however, the detailed mechanism is still largely unknown. Here, we created mice with adipocyte-specific deletion of EPO receptor. These mice exhibited obesity and decreased glucose tolerance and insulin sensitivity, especially when fed a high-fat diet. Moreover, EPO increased oxidative metabolism, fatty acid oxidation, and key metabolic genes in adipocytes and in white adipose tissue from diet-induced obese wild-type mice. Increased metabolic activity by EPO is associated with induction of brown fat-like features in white adipocytes, as demonstrated by increases in brown fat gene expression, mitochondrial content, and uncoupled respiration. Peroxisome proliferator-activated receptor (PPAR)α was found to mediate EPO activity because a PPARα antagonist impaired EPO-mediated induction of brown fat-like gene expression and uncoupled respiration. PPARα also cooperates with Sirt1 activated by EPO through modulating the NAD+ level to regulate metabolic activity. PPARα targets, including PPARγ coactivator 1α, uncoupling protein 1, and carnitine palmitoyltransferase 1α, were increased by EPO but impaired by Sirt1 knockdown. Sirt1 knockdown also attenuated adipose response to EPO. Collectively, EPO, as a novel regulator of adipose energy homeostasis via these metabolism coregulators, provides a potential therapeutic strategy to protect against obesity and metabolic disorders.

Topics: 3T3-L1 Cells; Adipocytes, White; Animals; Carnitine O-Palmitoyltransferase; Diet, High-Fat; Erythropoietin; Ion Channels; Lipid Metabolism; Metabolic Diseases; Mice; Mice, Knockout; Mitochondria; Mitochondrial Proteins; Obesity; Oxidation-Reduction; Oxygen Consumption; PPAR alpha; Receptors, Erythropoietin; Sirtuin 1; Uncoupling Protein 1

Nilotinib (Tasigna) is a second-generation BCR-ABL kinase inhibitor, recently introduced and used for the treatment of chronic or accelerated phase CML patients, intolerant or resistant to imatinib. This treatment represents and important step forward for the disease control of such patients but can lead to side effects, sometimes serious, which can limit its optimal use. We propose here some guidelines that might be of help in daily practice, in order to manage properly these side effects.

Topics: Antineoplastic Agents; Benzamides; Drug Eruptions; Drug Interactions; Drug Resistance, Neoplasm; Erythropoietin; Fertility; Food-Drug Interactions; France; Granulocyte Colony-Stimulating Factor; Heart Diseases; Humans; Imatinib Mesylate; Leukemia, Myelogenous, Chronic, BCR-ABL Positive; Metabolic Diseases; Neutropenia; Piperazines; Protein Kinase Inhibitors; Protein-Tyrosine Kinases; Pyrimidines; Recombinant Proteins

Comorbid conditions that develop during chronic renal insufficiency (CRI) contribute to the high morbidity and mortality among patients with end-stage renal disease (ESRD). Thus, appropriate management during CRI may lead to improved ESRD outcomes. A retrospective cohort study was performed to describe the management of patients with CRI. A total of 602 patients with CRI (creatinine > or =1.5 mg/dl for women and > or =2.0 mg/dl for men) were seen between October 1994 and September 1998 at five nephrology outpatient clinics in the Boston area. The mean (SD) age of the patients was 63 (15.5) yr, and 53% were male. At the first nephrology visit, mean (SD) serum creatinine was 3.2 (1.6) mg/dl, and mean (SD) predicted GFR was 22.3 (8.9) ml/min per 1.73 m(2). Laboratory tests for iron levels were performed in only 18% of patients, serum parathyroid hormone levels were obtained in only 15%, lipid studies were obtained in fewer than half, and among patients with diabetes, only 28% had a glycosylated hemoglobin level measured. A hematocrit <30% was present in 38%, and abnormal calcium-phosphorus metabolism was noted in 55%. Only 59% of patients who had hematocrit <30% received recombinant human erythropoietin. Among patients who received recombinant human erythropoietin, only 47% received iron. Angiotensin-converting enzyme inhibitor use was recorded for only 65% of patients with diabetes (49% of patients overall). Among patients who were known to have progressed to ESRD, only 41% had permanent access placed before initiation of dialysis. There seems to be room for improvement in the management of patients with CRI, which could result in a slower rate of progression of CRI and reduced severity of comorbid conditions.

Topics: Aged; Anemia; Angiotensin-Converting Enzyme Inhibitors; Cohort Studies; Erythropoietin; Female; Humans; Kidney Failure, Chronic; Male; Metabolic Diseases; Middle Aged; Nephrology; New England; Prevalence; Prospective Studies; Recombinant Proteins; Renal Dialysis; Time Factors

Topics: Aluminum; Anemia; Bone Diseases, Metabolic; Deferoxamine; Erythropoietin; Humans; Iron; Kidney Failure, Chronic; Metabolic Diseases; Recombinant Proteins; Renal Dialysis

Topics: Anemia; Erythrocyte Aging; Erythropoietin; Heme; Hemoglobins; Hemolysis; Humans; Iron; Kidney Diseases; Kidney Failure, Chronic; Metabolic Diseases; Porphyrins; Uremia