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https://www.readbyqxmd.com/read/29904289/identifying-suspected-familial-chylomicronemia-syndrome
#1
Ronak Rengarajan, Peter A McCullough, Anima Chowdhury, Kristen M Tecson
Familial chylomicronemia syndrome (FCS) is a rare lipid disorder posing significant clinical burdens on patients. Due to its rarity, variety of presentations, and lack of universal diagnostic criteria, patients see an average of five physicians before diagnosis. We screened adults for a triglyceride level ≥1000 mg/dL from September 2015 to September 2016 and a history of pancreatitis and performed a thorough chart review on those who met the criteria. An adjudication panel used a definition that also called for supportive information including history of hypertriglyceridemia or family history of pancreatitis/hypertriglyceridemia...
July 2018: Proceedings of the Baylor University Medical Center
https://www.readbyqxmd.com/read/29878904/towards-more-specific-treatment-for-diabetic-dyslipidemia
#2
Valentina Rodriguez, Jonathan D Newman, Arthur Z Schwartzbard
PURPOSE OF REVIEW: Treatment of diabetic dyslipidemia is necessary because of its impact on cardiovascular disease, which is the leading cause of death in patients with diabetes. In the past, standard treatment of diabetic dyslipidemia focused only on correcting lipids. Although this remains the mainstay of treatment, because new antihyperglycemic treatments reduce cardiovascular events with minimal effect on dyslipidemia, a new approach is both timely and relevant. RECENT FINDINGS: LDL-lowering remains the focus of treatment for diabetic dyslipidemia, especially in patients with both diabetes and cardiovascular disease (CVD)...
June 6, 2018: Current Opinion in Lipidology
https://www.readbyqxmd.com/read/29874528/a-placebo-controlled-trial-of-bezafibrate-in-primary-biliary-cholangitis
#3
RANDOMIZED CONTROLLED TRIAL
Christophe Corpechot, Olivier Chazouillères, Alexandra Rousseau, Antonia Le Gruyer, François Habersetzer, Philippe Mathurin, Odile Goria, Pascal Potier, Anne Minello, Christine Silvain, Armand Abergel, Maryline Debette-Gratien, Dominique Larrey, Olivier Roux, Jean-Pierre Bronowicki, Jérôme Boursier, Victor de Ledinghen, Alexandra Heurgue-Berlot, Eric Nguyen-Khac, Fabien Zoulim, Isabelle Ollivier-Hourmand, Jean-Pierre Zarski, Gisèle Nkontchou, Sara Lemoinne, Lydie Humbert, Dominique Rainteau, Guillaume Lefèvre, Luc de Chaisemartin, Sylvie Chollet-Martin, Farid Gaouar, Farid-Hakeem Admane, Tabassome Simon, Raoul Poupon
BACKGROUND: Patients with primary biliary cholangitis who have an inadequate response to therapy with ursodeoxycholic acid are at high risk for disease progression. Fibrates, which are agonists of peroxisome proliferator-activated receptors, in combination with ursodeoxycholic acid, have shown potential benefit in patients with this condition. METHODS: In this 24-month, double-blind, placebo-controlled, phase 3 trial, we randomly assigned 100 patients who had had an inadequate response to ursodeoxycholic acid according to the Paris 2 criteria to receive bezafibrate at a daily dose of 400 mg (50 patients), or placebo (50 patients), in addition to continued treatment with ursodeoxycholic acid...
June 7, 2018: New England Journal of Medicine
https://www.readbyqxmd.com/read/29865996/the-ldl-receptor-and-its-molecular-properties-from-theory-to-novel-biochemical-and-pharmacological-approaches-in-reducing-ldl-cholesterol
#4
Dimitrios Petroglou, Ilias Kanellos, Christos Savopoulos, Georgia Kaiafa, Anastasios Chrysochoou, Panagiotis Skantzis, Stylianos Daios, Apostolos I Hatzitolios, Georgios Giannoglou
Background The Low Density Lipoprotein (LDL) Receptor (LDL-R) is a transmembrane protein playing a crucial role in effective lipid homeostasis. Various therapeutic agents has been used in management of dyslipidemias, however the outcome of therapeutic target is debated. Objective The aim of this review is to summarize and fully understand the current concept regarding LDL-R and its molecular properties, metabolic pathway, factors affecting LDL-R activity and all available pharmacological interventions. Additionally, non-lipid related properties of LDL-R are also referred...
June 3, 2018: Current Medicinal Chemistry
https://www.readbyqxmd.com/read/29858856/diabetes-and-lipid-metabolism
#5
REVIEW
Vasilios G Athyros, Michael Doumas, Konstantinos P Imprialos, Konstantinos Stavropoulos, Eleni Georgianou, Alexandra Katsimardou, Asterios Karagiannis
The authors review the association between diabetes mellitus (DM) and aberrations of lipid metabolism related to DM, diabetic dyslipidemia (DD). DM is considered as a major health burden worldwide and one of the most important modifiable cardiovascular disease (CVD) risk factors. This applies to both the developed and the developing countries, especially the latter. While patients with type 1 DM, 10% of all DM cases, usually do not have dyslipidemia, DD is frequent among patients with type 2 DM (T2DM) (prevalence > 75%) and is mainly a mixed dyslipidemia [increase in triglycerides (TGs), low high-density lipoprotein cholesterol (HDL-C), and small-dense (atherogenic), low-density lipoprotein cholesterol (LDL-C) particles]...
March 2018: Hormones: International Journal of Endocrinology and Metabolism
https://www.readbyqxmd.com/read/29847748/peroxisome-proliferator-activated-receptor-alpha-mediated-drug-toxicity-in-the-liver
#6
Maka S Hedrington, Stephen N Davis
Drug-induced hepatic injury is the most common cause of acute liver failure in the United States. Included among the approximately 900 natural and synthetic substances that have shown hepatotoxicity are peroxisome proliferator-activated receptor alpha (PPARα)-mediated drugs. Areas covered: This review will focus on fibrates - PPARα agonists and their implication in causing liver injury. Expert opinion: Compelling evidence for fibrate-induced hepatotoxicity is not available. Results have been variable with several large randomized clinical trials reporting similar elevations of plasma transaminase levels in fibrate or placebo treated groups...
May 30, 2018: Expert Opinion on Drug Metabolism & Toxicology
https://www.readbyqxmd.com/read/29842811/pharmacological-treatment-options-for-severe-hypertriglyceridemia-and-familial-chylomicronemia-syndrome
#7
Rabia Chaudry, Adie Viljoen, Anthony S Wierzbicki
A spectrum of disorders, ranging from rare severe cases of homozygous null lipoprotein lipase deficiency (LPLD) -familial chylomicronemia syndrome (FCS) to heterozygous missense LPLD or polygenic causes, result in hypertriglyceridemia and pancreatitis. The effects of mutations are exacerbated by environmental factors such as diet, pregnancy and insulin resistance. Areas covered: In this review, authors discuss chronic treatment of FCS by ultra-low fat diets allied with the use of fibrates, omega-3 fatty acids, niacin, statins and insulin-sensitising therapies depending on the extent of residual LPL activity; novel therapies in development target triglyceride-rich lipoprotein particle clearance...
May 29, 2018: Expert Review of Clinical Pharmacology
https://www.readbyqxmd.com/read/29791572/is-lipid-accumulation-product-associated-with-an-atherogenic-lipoprotein-profile-in-brazilian-subjects
#8
Flavia De Conti Cartolano, Caroline Pappiani, Maria Camila Prupper de Freitas, Antonio M Figueiredo Neto, Antônio Augusto Ferreira Carioca, Nágila Raquel Teixeira Damasceno
BACKGROUND: Lipid accumulation product (LAP), a simple and low-cost tool, is a novel biomarker of central lipid accumulation and represents a potential surrogate marker for atherogenic lipoprotein profile. However, its association with lipoprotein subfractions has not been described in the literature. OBJECTIVE: To determine whether LAP index could be used as a marker of low- and high-density lipoprotein (LDL and HDL) size in Brazilian individuals. METHODS: This cross-sectional study included patients (n = 351) of both sexes and age between 30-74 years...
April 2018: Arquivos Brasileiros de Cardiologia
https://www.readbyqxmd.com/read/29790245/p465l-ppar%C3%AE-mutation-confers-partial-resistance-to-the-hypolipidemic-action-of-fibrates
#9
Sergio Rodriguez-Cuenca, Stefania Carobbio, Gwendolyn Barceló-Coblijn, Xavier Prieur, Joana Relat, Ramon Amat, Mark Campbell, Ana Rita Dias, Myriam Bahri, Sarah L Gray, Antonio Vidal-Puig
Familial partial lipodystrophic syndrome 3 (FPLD3) is associated with mutations in the transcription factor PPARγ. One of these mutations, the P467L, confers a dominant negative effect. We and others have previously investigated the pathophysiology associated to this mutation using a humanised mouse model that recapitulates most of the clinical symptoms observed in patients when phenotyped under different experimental conditions. One of the key clinical manifestations observed both, in humans and mouse models, is the ectopic accumulation of fat in the liver...
May 22, 2018: Diabetes, Obesity & Metabolism
https://www.readbyqxmd.com/read/29789212/fibrates-in-primary-prevention-of-cardiovascular-disease-comments-on-the-results-of-a-systematic-review-of-the-cochrane-collaboration
#10
Angel Brea, Jesús Millán, Juan F Ascaso, Mariano Blasco, Angel Díaz, Antonio Hernández-Mijares, Teresa Mantilla, Juan C Pedro-Botet, Xavier Pintó
Fibrates are drugs that reduce triglycerides, elevate high-density lipoproteins, as well as decrease small, dense LDL particles. The results of a study have recently been published by the Cochrane Collaboration on fibrates efficacy and safety in the primary prevention of cardiovascular disease. This study includes a systematic review and a meta-analysis of 6 studies (16,135 patients) that evaluated the clinical benefits of fibrates compared to placebo use or other lipid-lowering drugs. This review showed evidence of a protective effect of the fibrates compared with placebo as regards a reduction 16% of a compound objective of death due to cardiovascular disease, non-fatal myocardial infarction, or non-fatal cerebrovascular accident (NNT: 112), and that reduce coronary morbidity and mortality by 21% (NNT: 125)...
May 19, 2018: Clínica e Investigación en Arteriosclerosis
https://www.readbyqxmd.com/read/29789011/novel-phenoxazinones-as-potent-agonist-of-ppar-%C3%AE-design-synthesis-molecular-docking-and-in-vivo-studies
#11
David I Ugwu, Uchechukwu C Okoro, Narendra K Mishra, Sunday N Okafor
BACKGROUND: The use of statin, a 3-hydroxy-3-methylglutaryl coenzyme A reductase inhibitor for the treatment of dyslipidemia has been associated with dose limiting hepatoxicity, mytotoxicity and tolerability due to myalgias thereby necessitating the synthesis of new drug candidates for the treatment of lipid disorder. METHODS: The reaction of appropriate benzenesulphonamide with substituted phenoxazinone in the presence of phenylboronic acid gave the targeted compounds...
May 22, 2018: Lipids in Health and Disease
https://www.readbyqxmd.com/read/29784023/delayed-presentation-of-severe-rhabdomyolysis-leading-to-acute-kidney-injury-following-atorvastatin-gemfibrozil-combination-therapy-a-case-report
#12
Chamara Dalugama, Manoji Pathirage, S A M Kularatne
BACKGROUND: Rhabdomyolysis is a rare but serious complication of lipid-lowering therapy. Statin and fibrate combination increases the risk of rhabdomyolysis possibly by pharmacodynamic interactions. Advanced age, diabetes, hypothyroidism, polypharmacy, and renal impairment are known to increase the risk of rhabdomyolysis. Management strategies include fluid resuscitation and urine alkalinization. Renal indications such as refractory hyperkalemia, acidosis, fluid overload, or uremic complications mandate renal replacement therapy in rhabdomyolysis...
May 22, 2018: Journal of Medical Case Reports
https://www.readbyqxmd.com/read/29769239/hypertriglyceridemia-and-cardiovascular-risk-a-cautionary-note-about-metabolic-confounding
#13
Allan D Sniderman, Patrick Couture, Seth B Martin, Jacqueline DeGraaf, Patrick R Lawler, William C Cromwell, John T Wilkins, George Thanassoulis
Triglycerides are the conventional tool to measure very low-density lipoproteins (VLDL) whereas low-density lipoprotein cholesterol (LDL-C) is the conventional tool to measure low-density lipoproteins (LDL). Multiple epidemiological studies, including a series of genetically based analyses, have demonstrated cardiovascular risk is related to triglycerides independently of LDL-C and this has led to a series of new therapeutic agents designed specifically to reduce plasma triglycerides. The triglyceride hypothesis posits that increased levels of triglycerides increase cardiovascular risk and decreasing plasma triglycerides decreases cardiovascular risk...
May 16, 2018: Journal of Lipid Research
https://www.readbyqxmd.com/read/29760790/anticancer-properties-of-fenofibrate-a-repurposing-use
#14
REVIEW
Xin Lian, Gang Wang, Honglan Zhou, Zongyu Zheng, Yaowen Fu, Lu Cai
Cancer is a leading cause of death throughout the world, and cancer therapy remains a big medical challenge in terms of both its therapeutic efficacy and safety. Therefore, to find out a safe anticancer drug has been long goal for oncologist and medical scientists. Among clinically used medicines with no or little toxicity, fenofibrate is a drug of the fibrate class that plays an important role in lowering the levels of serum cholesterol and triglycerides while elevating the levels of high-density lipoproteins...
2018: Journal of Cancer
https://www.readbyqxmd.com/read/29737015/therapeutic-agents-targeting-cardiometabolic-risk-for-preventing-and-treating-atherosclerotic-cardiovascular-diseases
#15
Benoit J Arsenault, Nicolas Perrot, Rishi Puri
Targeting atherogenic lipoprotein levels with statins remains the current cornerstone of atherosclerotic cardiovascular disease (ACVD) management. In patients at high ACVD risk who cannot achieve the desired low-density lipoprotein (LDL) cholesterol target, the addition of compounds such as ezetimibe and proprotein subtilisin/kexin type-9 (PCSK9) inhibitors incrementally lowers cardiovascular risk. New glucose-lowering drugs such as glucacon-like peptide-1 receptor (GLP1R) agonists and sodium-glucose co-transporter-2 (SGLT2) inhibitors were also shown to improve cardiometabolic risk factors and provide cardiovascular benefits in patients with type 2 diabetes...
May 8, 2018: Clinical Pharmacology and Therapeutics
https://www.readbyqxmd.com/read/29735610/reduction-in-secretion-of-very-low-density-lipoprotein-triacylglycerol-by-a-matrix-metalloproteinase-inhibitor-in-a-rat-model-of-diet-induced-hypertriglyceridemia
#16
Yoichi Kawashima, Yoshihiro Eguchi, Tohru Yamazaki, Minako Karahashi, Hiroshi Kawai, Naomi Kudo
Matrix metalloproteinase inhibitors (MMPIs) reduced serum triacylglycerol (TAG) levels in streptozotocin-induced diabetic rats and Zucker fa/fa rats in our previous study. However, the mechanisms underlying TAG reduction by MMPIs remain unclear. The present study aimed to elucidate the mechanism by which F81-1144b, a MMPI, lowers serum TAG levels in an animal model of high sucrose diet (HSD)-induced hypertriglyceridemia. F81-1144b was repeatedly administered to rats fed HSD, and its effects were evaluated on TAG levels in serum and the liver, very low density lipoprotein (VLDL) secretion, de novo fatty acid (FA) synthesis in the liver, and the expression of genes regulating the metabolism of FA, TAG, and VLDL in the liver and serum...
May 7, 2018: Journal of Pharmacology and Experimental Therapeutics
https://www.readbyqxmd.com/read/29691599/-primary-biliary-cholangitis-established-and-novel-therapies
#17
REVIEW
M Vetter, A E Kremer
BACKGROUND: Patients with primary biliary cholangitis (PBC, formerly primary biliary cirrhosis) and insufficient treatment response or risk factors exhibit a remarkably increased risk for disease progression and associated complications. Furthermore, extrahepatic manifestations may considerably reduce quality of life in affected patients. OBJECTIVES: This article presents an overview on standard therapy with ursodeoxycholic acid (UDCA) and further therapeutic options in patients with insufficient treatment response...
June 2018: Der Internist
https://www.readbyqxmd.com/read/29681002/the-influence-of-fibrate-initiation-on-inr-and-warfarin-dose-in-patients-receiving-chronic-warfarin-therapy
#18
John F Polnak, Thomas Delate, Nathan P Clark
Several drug interaction compendia report a risk of warfarin potentiation after initiation of a fibrate; however, the evidence of this interaction is limited. The objective of this study was to evaluate warfarin dose and international normalized ratio (INR) response among a large sample of patients receiving chronic warfarin who initiated a fibrate. This was a retrospective, one-sample, pre-to-post study. Adult patients who were receiving chronic warfarin therapy at the time of gemfibrozil or fenofibrate dispensing between 1/1/2000 and 3/31/2016 were included...
April 21, 2018: Journal of Thrombosis and Thrombolysis
https://www.readbyqxmd.com/read/29671538/stable-coronary-artery-disease-treatment
#19
Michael M Braun, William A Stevens, Craig H Barstow
Stable coronary artery disease refers to a reversible supply/demand mismatch related to ischemia, a history of myocardial infarction, or the presence of plaque documented by catheterization or computed tomography angiography. Patients are considered stable if they are asymptomatic or their symptoms are controlled by medications or revascularization. Treatment involves risk factor management, antiplatelet therapy, and antianginal medications. Tobacco cessation, exercise, and weight loss are the most important lifestyle modifications...
March 15, 2018: American Family Physician
https://www.readbyqxmd.com/read/29669526/the-effect-of-fenofibrate-on-early-retinal-nerve-fiber-layer-loss-in-type-2-diabetic-patients-a-case-control-study
#20
Rui Shi, Lei Zhao, Yun Qi
BACKGROUND: Previous studies suggested that use of fenofibrate could significantly reduce the rate of progression into diabetic retinopathy (DR), and that retinal nerve fiber layer (RNFL) loss, which has been considered an important indicator for retinal neurodegeneration, might precede microvascular changes. The aim of this study was to assess the effect(s) of fenofibrate on RNFL thickness at early stage of DR in patients with type 2 diabetes mellitus (DM). METHODS: In this retrospective matched case-control study we included a cohort of 89 patients with type 2 DM, aged 40 or above, between Jan 1, 2017 and March 31, 2017...
April 18, 2018: BMC Ophthalmology
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