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Albert Parés
Primary cholangitis (cirrhosis) is a chronic cholestatic disease with an unquestionable female predominance. It is characterised by inflammation of the small and medium size bile ducts, and can eventually progress to cirrhosis. Most patients remain asymptomatic and are diagnosed by the casual finding of an anicteric biochemical cholestasis with increased alkaline phosphatase. The pathogenesis is unknown and of presumed autoimmune origin in genetic susceptible subjects. M2-type antimitochondrial antibodies, and specific antinuclear antibodies (gp210 and Sp100) are typical and specific of the disease...
March 8, 2018: Medicina Clínica
M Majerczyk, P Kocełak, P Choręza, H Arabzada, A J Owczarek, M Bożentowicz-Wikarek, A Brzozowska, A Szybalska, M Puzianowska-Kuźnicka, T Grodzicki, A Więcek, M Olszanecka-Glinianowicz, J Chudek
PURPOSE: Elevated plasma concentration of retinol binding protein 4 (RBP4) has recently emerged as a potential risk factor as a component of developing metabolic syndrome (MS). Therefore, this study aimed to analyse the relationship between components of MS and concentrations of plasma RBP4 in a population of subjects 65 years and older. METHODS: The study sample consisted of 3038 (1591 male) participants of the PolSenior study, aged 65 years and older. Serum lipid profile, concentrations of RBP4, glucose, insulin, C-reactive protein, IL-6, and activity of aminotransferases were measured...
March 9, 2018: Journal of Endocrinological Investigation
Caio Mauricio Mendes de Cordova, Ernani Tiarajú de Santa Helena, Caroline Galgowski, Vitor Holmo Figueira, Gabrielle Bortoli Setter, Marcello Ricardo Paulista Markus, Carsten Oliver Schmidt, Henry Völzke, Till Ittermann
A simple equation established by Cordova & Cordova (LDL-COR) was developed to provide an improved estimation of LDL-cholesterol in a large Brazilian laboratory database. We evaluated this new equation in a general population cohort in Pomerania, north-eastern Germany (SHIP Study) compared to other existing formulas (Anandaraja, Teerakanchana, Chen, Hattori, Martin, Friedewald and Ahmadi), and its power in the prediction of death by atherosclerosis related events as the primary outcome. Analysis was conducted on a cohort of 4075 individuals considering age, gender, use of lipid lowering therapy and associated co-morbidities such as diabetes, hepatic, kidney and thyroid disease...
March 8, 2018: Scandinavian Journal of Clinical and Laboratory Investigation
Andrew A Nierenberg, Sharmin A Ghaznavi, Isadora Sande Mathias, Kristen K Ellard, Jessica A Janos, Louisa G Sylvia
Peroxisome proliferator-activated receptor gamma coactivator-1 alpha (PGC-1 alpha) is a protein that regulates metabolism and inflammation by activating nuclear receptors, especially the family of peroxisome proliferator-activated receptors (PPARs). PGC-1 alpha and PPARs also regulate mitochondrial biogenesis, cellular energy production, thermogenesis, and lipid metabolism. Brain energy metabolism may also be regulated in part by the interaction between PGC-1 alpha and PPARs. Because neurodegenerative diseases (Huntington's disease, Parkinson's disease, and amyotrophic lateral sclerosis) and bipolar disorder have been associated with dysregulated mitochondrial and brain energy metabolism, PGC-1 alpha may represent a potential drug target for these conditions...
January 10, 2018: Biological Psychiatry
Michel P Hermans, Paul Valensi
PURPOSE OF REVIEW: The aim of this review is to describe in diabetic patients the determinants underlying atherogenic dyslipidemia, a complex dyslipidemia defined as the coexistence of fasting hypertriglyceridemia and low high-density lipoprotein cholesterol level. Atherogenic dyslipidemia is often comorbid with hyperglycemia in patients with the common form of type 2 diabetes mellitus (T2DM), namely that associated with obesity, insulin resistance, hyperinsulinemia and the metabolic syndrome phenotype...
April 2018: Current Opinion in Endocrinology, Diabetes, and Obesity
Priska Stahel, Changting Xiao, Robert A Hegele, Gary F Lewis
Despite the effectiveness of low-density lipoprotein (LDL)-lowering strategies for the treatment of diabetic dyslipidemia, significant residual risk of atherosclerotic cardiovascular disease remains. Residual risk might in part be explained by lipid abnormalities that go beyond LDL cholesterol elevation, collectively termed the "atherogenic dyslipidemia complex (ADC)," consisting of hypertriglyceridemia, elevated small dense LDL particles, reduced high-density lipoprotein cholesterol, and high-density lipoprotein particle numbers, increased remnant lipoproteins, and postprandial hyperlipidemia...
December 15, 2017: Canadian Journal of Cardiology
Xinran Wang, Wei Li, Lijuan Hao, Honglei Xie, Chenzhou Hao, Chunchi Liu, Wenyan Li, Xuqiong Xiong, Dongmei Zhao
Epidemiological studies have identified that high levels of low-density lipoprotein-cholesterol (LDL-C) and low levels of high-density lipoprotein-cholesterol (HDL-C) are two independent causes of cardiovascular disease (CVD). Statins, niacin and fibrate are used for the treatment of CVD. However, some defects are shown in the treatment process. Thus, there is a demand for better treatment strategies that confer preferable efficacy with fewer side effects. Cholesteryl ester transfer protein (CETP) promotes the movement of CEs from HDL to LDL and VLDL in exchange for triglycerides (TGs)...
February 9, 2018: Expert Opinion on Therapeutic Patents
Niki Katsiki, Athanasios D Giannoukas, Vasilios G Athyros, Dimitri P Mikhailidis
Peripheral artery disease (PAD) is characterized by increased cardiovascular (CV) risk, limb morbidity and all-cause mortality. According to the current guidelines (2016) of the American Heart Association/American College of Cardiology on the management of PAD patients, statin therapy is recommended for PAD patients in order to treat dyslipidemia and reduce CV risk. The present narrative review discusses the use of statins and other lipid-lowering drugs such as ezetimibe, fibrates, niacin, anacetrapib and proprotein convertase subtilisin/kexin type 9 (PCSK9) inhibitors in PAD patients in terms of both CV and limb outcomes...
January 31, 2018: Current Opinion in Pharmacology
Jesus Millan, Xavier Pintó, Angel Brea, Mariano Blasco, Antonio Hernandez Mijares, Juan Ascaso, Angel Diaz, Teresa Mantilla, Juan Pedro-Botet
Fibrates are a group of drugs that are known mainly for reducing triglycerides, increasing high density lipoproteins (HDL), and reducing the fraction of small, dense LDL particles. The results of a Cochrane Collaboration study have recently been published on their efficacy and safety in the secondary prevention of severe cardiovascular accidents, including coronary and cerebrovascular disease. The study included randomised clinical trials in which the fibrate was compared with placebo or with no treatment. Clinical trials comparing two different fibrates were excluded...
January 30, 2018: Clínica e Investigación en Arteriosclerosis
Laurel A Copeland, C Scott Swendsen, Dawn M Sears, Andrea A MacCarthy, Catherine J McNeal
Conventional wisdom supports prescribing "fibrates before statins", that is, prioritizing treatment of hypertriglyceridemia (hTG) to prevent pancreatitis ahead of low-density lipoprotein cholesterol to prevent coronary heart disease. The relationship between hTG and acute pancreatitis, however, may not support this approach to clinical management. This study analyzed administrative data from the Veterans Health Administration for evidence of (1) temporal association between assessed triglycerides level and days to acute pancreatitis admission; (2) association between hTG and outcomes in the year after hospitalization for acute pancreatitis; (3) relative rates of prescription of fibrates vs statins in patients with acute pancreatitis; (4) association of prescription of fibrates alone versus fibrates with statins or statins alone with rates of adverse outcomes after hospitalization for acute pancreatitis...
2018: PloS One
Donatella Zodda, Rosario Giammona, Silvia Schifilliti
Prevention and treatment of dyslipidemia should be considered as an integral part of individual cardiovascular prevention interventions, which should be addressed primarily to those at higher risk who benefit most. To date, statins remain the first-choice therapy, as they have been shown to reduce the risk of major vascular events by lowering low-density lipoprotein cholesterol (LDL-C). However, due to adherence to statin therapy or statin resistance, many patients do not reach LDL-C target levels. Ezetimibe, fibrates, and nicotinic acid represent the second-choice drugs to be used in combination with statins if lipid targets cannot be reached...
January 21, 2018: Pharmacy (Basel, Switzerland)
Edgar Shaghoulian
I conjecture a high-temperature-low-temperature duality for conformal field theories defined on circle fibrations like S^{3} and its lens space family. The duality is an exchange between the thermal circle and the fiber circle in the limit where both are small. The conjecture is motivated by the fact that π_{1}(S^{3}/Z_{p→∞})=Z=π_{1}(S^{1}×S^{2}) and the Gromov-Hausdorff distance between S^{3}/Z_{p→∞} and S^{1}/Z_{p→∞}×S^{2} vanishes. Several checks of the conjecture are provided: free fields, N=1 theories in four dimensions (which shows that the Di Pietro-Komargodski supersymmetric Cardy formula and its generalizations are given exactly by a supersymmetric Casimir energy), N=4 super Yang-Mills at strong coupling, and the six-dimensional N=(2,0) theory...
September 29, 2017: Physical Review Letters
Y W Shi, H Ma
With the progress in detection methods and the update of diagnostic and therapeutic concepts, more and more patients with primary biliary cholangitis (PBC) have been diagnosed and treated. A high proportion of PBC patients, however, progress to liver decompensation, with an increased risk of liver transplantation and death and a significant reduction in long-term survival. These patients need early diagnosis and urgent treatment. This article discusses how to identify the PBC patients with poor prognosis early from the aspects of biochemical response, disease features, and biomarkers, and reviews the progress in related complementary therapies and new drugs including Ocaliva, Fibrates, UDCA-derived drugs, and molecular targeted drugs...
November 20, 2017: Zhonghua Gan Zang Bing za Zhi, Zhonghua Ganzangbing Zazhi, Chinese Journal of Hepatology
Y M Li, Q X Wang, X Ma
Primary biliary cholangitis (PBC) is an autoimmune liver disease mainly involving intrahepatic interlobular bile ducts and can progress to liver fibrosis, liver cirrhosis, and even liver failure. Ursodeoxycholic acid (UDCA) is the first-line therapeutic drug for PBC and can delay disease progression, but as high as 40% of patients have suboptimal response to UDCA. Obeticholic acid, a farnesoid X receptor agonist, has been approved by FDA in May 2016 for patients who have no response to UDCA treatment or cannot tolerate such treatment...
November 20, 2017: Zhonghua Gan Zang Bing za Zhi, Zhonghua Ganzangbing Zazhi, Chinese Journal of Hepatology
Cynthia Levy, Keith D Lindor
Approximately one-third of patients with primary biliary cholangitis (PBC) fail to respond to ursodeoxycholic acid (UDCA) and are at risk for progression to biliary cirrhosis and end-stage liver disease. In this paper by Pares et al., the authors evaluate the effect of long-term use of bezafibrate in patients with primary biliary cholangitis (PBC) and inadequate response to UDCA. They found that addition of bezafibrate led to normalization of serum alkaline phosphatase in half of the study subjects and major improvement in pruritus...
January 2018: American Journal of Gastroenterology
Masoud Delashoub, Mojtaba Ziaee, Arash Khorrami, Seyed Mahdi Banan-Khojasteh
PURPOSE: Fibrates are drugs widely used for the treatment of hyperlipidemic disorders. Previous studies on a novel analogue of clofibrate, called silafibrate, have shown good lipid lowering effects. This study was designed to assess the role of silafibrate as a peroxisome proliferator-activated receptors (PPARs) agonist on sperm health and spermatogenesis in adult male rats. MATERIAL AND METHODS: Seventy male Wistar rats were randomly allocated into 7 groups: Cl-10, Cl-20, and Cl-40 mg/kg/day (clofibrate); Si-10, Si-20, and Si-40 mg/kg/day (silafibrate); and C, control...
January 3, 2018: Urology Journal
Ishfaq A Bukhari, Abdulrahman A Almotrefi, Osama Y Mohamed, Abeer A Al-Masri, Saeed Ahmed Sheikh
Fenofibrate is a peroxisome proliferator-activated receptor (PPAR)-α activator that lowers triglycerides and influences cytochrome P-450 (CYP-450) epoxygenase dependent arachidonic acid (AA) metabolism. CYP-450 epoxygenase metabolizes AA to epoxyeicosatrienoic acids (EETs). EETs have coronary dilating, cardiac and renal protective properties. Fibrates possess similar properties due to their CYP-450 epoxygenase inducing properties that leads to increase in endogenous EETs production. In the current investigations fenofibrate (100 mg/kg, orally) for two weeks decreased ischemia/reperfusion (I/R)-induced premature ventricular contractions (PVCs), ventricular tachycardia (VT) and ventricular fibrillation (VF) in the isolated rat hearts...
December 31, 2017: Fundamental & Clinical Pharmacology
Marija Vavlukis, Sasko Kedev
BACKGROUND: Diabetic dyslipidemia has specifics that differ from dyslipidemia in patients without diabetes, which contributes to accelerated atherosclerosis equally as dysglycemia. The aim of this study was to deduce the interdependence of diabetic dyslipidemia and cardiovascular diseases (CVD), therapeutic strategies and the risk of diabetes development with statin therapy. METHOD: We conducted a literature review of English articles through PubMed, PubMed Central and Cochrane, on the role of diabetic dyslipidemia in atherosclerosis, the antilipemic treatment with statins, and the role of statin therapy in newly developed diabetes, by using key words: atherosclerosis, diabetes mellitus, diabetic dyslipidemia, CVD, statins, nicotinic acid, fibrates, PCSK9 inhibitors...
December 27, 2017: Current Pharmaceutical Design
Roberto Scicali, Antonino Di Pino, Viviana Ferrara, Francesca Urbano, Salvatore Piro, Agata Maria Rabuazzo, Francesco Purrello
Dyslipidemias represent a variety of quantitative and/or qualitative lipoprotein abnormalities. According to etiology, we distinguish primary dyslipidemias with strictly genetic background and secondary ones with their origin in other disease or pathological states. Diabetic dyslipidemia is a type of secondary dyslipidemia and plays an important role in determining the cardiovascular risk of subjects with type 2 diabetes. In these patients, insulin resistance is responsible for overproduction and secretion of atherogenic very low density lipoprotein...
March 2018: Acta Diabetologica
Preya J Patel, David Smith, Jason P Connor, Leigh U Horsfall, Kelly L Hayward, Fabrina Hossain, Suzanne Williams, Tracey Johnson, Katherine A Stuart, Nigel N Brown, Nivene Saad, Andrew D Clouston, Katharine M Irvine, Anthony W Russell, Patricia C Valery, Elizabeth E Powell
Aim: To examine the association between lifetime alcohol consumption and significant liver disease in type 2 diabetic patients with NAFLD. Methods: A cross-sectional study assessing 151 patients with NAFLD at risk of clinically significant liver disease. NAFLD fibrosis severity was classified by transient elastography; liver stiffness measurements ≥8.2 kPa defined significant fibrosis. Lifetime drinking history classified patients into nondrinkers, light drinkers (always ≤20 g/day), and moderate drinkers (any period with intake >20 g/day)...
2017: Canadian Journal of Gastroenterology & Hepatology
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