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https://www.readbyqxmd.com/read/29155776/differential-effects-of-lipid-lowering-drugs-in-modulating-morphology-of-cholesterol-particles
#1
Shanmugavel Madasamy, David Liu, Jason Lundry, Benjamin Alderete, Raymond Kong, J Paul Robinson, Alan H B Wu, Edward P Amento
Treatment of dyslipidemia patients with lipid-lowering drugs leads to a significant reduction in low-density lipoproteins (LDL) level and a low to moderate level of increase in high-density lipoprotein (HDL) cholesterol in plasma. However, a possible role of these drugs in altering morphology and distribution of cholesterol particles is poorly understood. Here, we describe the in vitro evaluation of lipid-lowering drug effects in modulating morphological features of cholesterol particles using the plaque array method in combination with imaging flow cytometry...
November 10, 2017: Journal of Visualized Experiments: JoVE
https://www.readbyqxmd.com/read/29141109/hepatic-ppar%C3%AE-mediates-the-major-metabolic-effects-of-wy-14643
#2
Guolin Li, Chad N Brocker, Cen Xie, Tingting Yan, Audrey Noguchi, Kristopher W Krausz, Rong Xiang, Frank J Gonzalez
BACKGROUND AND AIM: Peroxisome proliferator-activated receptor alpha (PPARα) is a molecular target of various fibrate drugs clinically used to lower serum lipids. However, the tissue-specific functions of PPARα remain to be elucidated. This study aimed to explore the tissue-specific functions of PPARα in response to Wy-14643. METHODS: A hepatocyte-specific Ppara knockout mouse line was used to explore the impact of hepatic PPARα activity on the systemic response to treatment with the potent PPARα agonist Wy-14643...
November 15, 2017: Journal of Gastroenterology and Hepatology
https://www.readbyqxmd.com/read/29117614/the-effect-of-hypolipidemic-agents-on-thyroid-autoimmunity-in-women-with-hashimoto-s-thyroiditis-treated-with-levothyroxine-and-selenomethionine
#3
Robert Krysiak, Witold Szkróbka, Bogusław Okopień
Background Levothyroxine and selenomethionine were found to reduce thyroid antibody titers in patients with Hashimoto's thyroiditis. The same effect was produced by intensive statin therapy. The aim of the present study was to assess whether hypolipidemic agents modulate the impact of thyroid hormone supplementation and selenomethionine on thyroid autoimmunity. Methods The study included 62 women with Hashimoto's thyroiditis treated for at least 6 months with levothyroxine and selenomethionine. On the basis of plasma lipids, women were divided into three groups: women with isolated hypercholesterolemia (group A; n=20), women with isolated hypertriglyceridemia (group B; n=17), and women with normal plasma lipids (group C; n=25)...
November 8, 2017: Experimental and Clinical Endocrinology & Diabetes
https://www.readbyqxmd.com/read/29113896/neuroinflammation-produced-by-heavy-alcohol-intake-is-due-to-loops-of-interactions-between-toll-like-4-and-tnf-receptors-peroxisome-proliferator-activated-receptors-and-the-central-melanocortin-system-a-novel-hypothesis-and-new-therapeutic-avenues
#4
Osvaldo Flores-Bastías, Eduardo Karahanian
Excessive alcohol intake induces an inflammatory response in the brain, via TNFα, TLR4 and NF-κB signaling pathways. It has been proposed that neuroinflammation would play a very important role in the development of alcohol addiction. In addition to stimulating the synthesis of inflammatory mediators such as IL-6, IL-1β and TNFα, NF-κB is capable of reducing the anti-inflammatory activity of PPARα and PPARγ. Reciprocally, PPARα, PPARγ and melanocortin 4 receptor (MC4R) can decrease the proinflammatory activity of NF-κB, establishing an interplay of inactivations between such nuclear factors and receptors...
November 4, 2017: Neuropharmacology
https://www.readbyqxmd.com/read/29110598/sirt1-as-a-therapeutic-target-in-diabetic-complications
#5
Justyna Strycharz, Żaneta Rygielska, Ewa Świderska, Józef Drzewoski, Janusz Szemraj, Leszek Szmigiero, Agnieszka Śliwińska
Background SIRT1 is an epigenetic enzyme involved in histone and non-histone protein deacetylation. It acts primarily as a metabolic sensor, which responses to changing energy status by deacetylating crucial transcription factors and cofactors. In this way, SIRT1 regulates mitochondrial function and biogenesis, oxidative stress, inflammation, apoptosis and cellular senescence. Disturbance of all of these phenomena promotes the pathogenesis of diabetic complications. These disorders are inseparably connected with chronic hyperglycemia, which possesses a strong epigenetic determinant...
November 6, 2017: Current Medicinal Chemistry
https://www.readbyqxmd.com/read/29096837/the-role-of-antisense-oligonucleotide-therapy-against-apolipoprotein-ciii-in-hypertriglyceridemia
#6
Ioanna Gouni-Berthold
Increased triglyceride levels (higher than ∼1000 mg/dL) are associated with an increased risk for pancreatitis. Apolipoprotein-CIII (apo-CIII) plays a key role in the metabolism of triglycerides and triglyceride-rich lipoproteins. While loss of function mutations in the gene encoding apo-CIII (APOC3) are associated with low triglyceride levels and a decreased risk for cardiovascular disease (CVD), overexpression of APOC3 is associated with hypertriglyceridemia. Although many drugs such as fibrates, statins and omega-3 fatty acids modestly decrease triglyceride levels (and apo-CIII concentrations), there are many patients who still have severe hypertriglyceridemia and are at risk for pancreatitis and potentially CVD...
November 2017: Atherosclerosis. Supplements
https://www.readbyqxmd.com/read/29059162/activation-of-ppar%C3%AE-by-clofibrate-sensitizes-pancreatic-cancer-cells-to-radiation-through-the-wnt-%C3%AE-catenin-pathway
#7
J Xue, W Zhu, J Song, Y Jiao, J Luo, C Yu, J Zhou, J Wu, M Chen, W-Q Ding, J Cao, S Zhang
Radiotherapy is emerging as an important modality for the local control of pancreatic cancer, but pancreatic cancer cell radioresistance remains a serious concern. Peroxisome proliferator-activated receptor α (PPARα) is a member of the PPAR nuclear hormone receptor superfamily, which can be activated by fibrate ligands. The clinical relevance of PPARα and its biological function in pancreatic cancer radiosensitivity have not been previously described. In this study, we examined PPARα expression in tissue samples of pancreatic cancer patients...
October 23, 2017: Oncogene
https://www.readbyqxmd.com/read/29043897/role-of-fibrate-drugs-in-the-prevention-of-diabetic-foot
#8
Robert Elkeles
No abstract text is available yet for this article.
October 2017: Journal of the Royal Society of Medicine
https://www.readbyqxmd.com/read/29016567/effects-of-bezafibrate-on-outcome-and-pruritus-in-primary-biliary-cholangitis-with-suboptimal-ursodeoxycholic-acid-response
#9
Anna Reig, Pilar Sesé, Albert Parés
OBJECTIVES: Adding fibrates improves liver biochemistries in patients with primary biliary cholangitis (PBC) and suboptimal response to ursodeoxycholic acid (UDCA). As there are no consistent data regarding the course and outcome, we have assessed the effects of the combined treatment with UDCA and bezafibrate on a long-term basis. METHODS: A total of 48 patients (45 female) with PBC treated with UDCA and alkaline phosphatase (ALP) above 1.5 times upper normal levels (× UNL) were treated with bezafibrate (400 mg/day) plus UDCA (13-16 mg/kg/day)...
October 10, 2017: American Journal of Gastroenterology
https://www.readbyqxmd.com/read/28993194/identification-of-a-selective-inhibitor-of-human-monocarboxylate-transporter-4
#10
Yuya Futagi, Masaki Kobayashi, Katsuya Narumi, Ayako Furugen, Ken Iseki
The human monocarboxylate transporters (hMCTs/SLC16As) mediate the uptake of various monocarboxylates. Several isoforms of hMCTs are expressed in cancerous tissue as well as in normal tissue. In cancerous tissue, hypoxia induces the expression of hMCT4, which transports the energetic metabolite l-lactate across the plasma membrane. Since hMCT4 is involved in pH regulation and the transport of l-lactate in cancer cells, an hMCT4 inhibitor could function as an anticancer agent. Although several non specific hMCT inhibitors have been developed, a selective hMCT4 inhibitor has not yet been identified...
October 6, 2017: Biochemical and Biophysical Research Communications
https://www.readbyqxmd.com/read/28978316/pemafibrate-k-877-a-novel-selective-peroxisome-proliferator-activated-receptor-alpha-modulator-for-management-of-atherogenic-dyslipidaemia
#11
REVIEW
Jean-Charles Fruchart
Despite best evidence-based treatment including statins, residual cardiovascular risk poses a major challenge for clinicians in the twenty first century. Atherogenic dyslipidaemia, in particular elevated triglycerides, a marker for increased triglyceride-rich lipoproteins and their remnants, is an important contributor to lipid-related residual risk, especially in insulin resistant conditions such as type 2 diabetes mellitus. Current therapeutic options include peroxisome proliferator-activated receptor alpha (PPARα) agonists, (fibrates), but these have low potency and limited selectivity for PPARα...
October 4, 2017: Cardiovascular Diabetology
https://www.readbyqxmd.com/read/28973556/clofibrate-decreases-bile-acids-in-livers-of-male-mice-by-increasing-biliary-bile-acid-excretion-in-a-ppar%C3%AE-dependent-manner
#12
Youcai Zhang, Andrew J Lickteig, Iván L Csanaky, Curtis D Klaassen
Fibrates and their receptor, namely peroxisome proliferator-activated receptor α (PPARα), have been reported to regulate bile acid (BA) synthesis and transport. However, the effect of fibrate treatment and PPARα activation on BA homeostasis remains controversial. In the present study, both wild-type (WT) and PPARα-null male mice were treated with clofibrate (CLOF) for 4 days to evaluate the effects of short-term PPARα activation on bile acid (BA) homeostasis. While a decrease in total BAs was observed in livers of CLOF-treated WT mice, it was not observed in PPARα-null mice...
September 13, 2017: Toxicological Sciences: An Official Journal of the Society of Toxicology
https://www.readbyqxmd.com/read/28957862/triglyceride-lowering-trials
#13
Anthony C Keech, Alicia J Jenkins
PURPOSE OF REVIEW: We provide an overview of current evidence about the independent role of high triglyceride levels for cardiovascular risk and for acute pancreatitis. RECENT FINDINGS: Natural experiments of Mendelian randomization have given us a deeper understanding about the molecular pathways involved in triglyceride metabolism. Individuals with low-triglyceride levels generally have lower rates of cardiovascular disease (CVD). There has been a significant growth in the development of new agents that modulate enzymes involved in a variety of aspects of triglyceride packaging into VLDL or chylomicron particles, and triglyceride catabolism...
September 27, 2017: Current Opinion in Lipidology
https://www.readbyqxmd.com/read/28952474/-pitavastatin-tolerability-and-advers-effect-profile
#14
Nevrez Koylan
There are many speculations about the safety of statins which are widely used drugs. In contrast, statins are safer than many widely used drugs. Rhabdomyolysis, the most important adverse event is closely related to plasma drug levels which take drug interactions into account. The most important drugs among interacting drugs are fibrates, antiretroviral drugs and macrolid antibiotics, and, pitavastatin seems to be more advantageous than other statins. Similarly, pitavastatin has better myopathy profile when compared to other statins...
April 2017: Türk Kardiyoloji Derneği Arşivi: Türk Kardiyoloji Derneğinin Yayın Organıdır
https://www.readbyqxmd.com/read/28946176/species-related-exposure-of-phase-ii-metabolite-gemfibrozil-1-o-%C3%AE-glucuronide-between-human-and-mice-a-net-induction-of-mouse-p450-activity-was-revealed
#15
Min Luo, Manyun Dai, Hante Lin, Minzhu Xie, Jiao Lin, Aiming Liu, Julin Yang
Gemfibrozil is a fibrate drug widely used for dyslipidemia associated with atherosclerosis. Clinically, both gemfibrozil and its phase II metabolite gemfibrozil1-O-β-glucuronide (gem-glu) are involved in drug-drug interaction (DDI). But the DDI risk caused by gem-glu between human and mice has not been compared. In this study, 6 volunteers were recruited and took therapeutic dose of gemfibrozil for 3 days for examination of the gemfibrozil and gem-glu level in human. Male mice were fed a gemfibrozil diet (0...
September 25, 2017: Biopharmaceutics & Drug Disposition
https://www.readbyqxmd.com/read/28941579/-fibrates-and-risk-of-venous-thromboembolism-case-no-case-study-in-french-pharmacovigilance-database
#16
Xavier Humbert, Charles Dolladille, Marion Sassier, Marie-Blanche Valnet-Rabier, Thierry Vial, Emmanuelle Guitton, Annabelle Page, Elodie Sole, Pascal Auriche, Antoine Coquerel, Joachim Alexandre, Sophie Fedrizzi
INTRODUCTION: Several studies have investigated the occurrence of venous thromboembolic events (phlebitis and pulmonary embolism) [VTE] and fibrates. Fibrates could be associated with VTE although published data are contradictory. The objective of this study is to confirm the link between VTE and fibrates. MATERIALS AND METHODS: Retrospective disproportionality analysis (case/non-case method) from observations recorded consecutively in the French pharmacovigilance database between 1985 and 2016...
August 1, 2017: Thérapie
https://www.readbyqxmd.com/read/28928170/effect-of-adding-bezafibrate-to-standard-lipid-lowering-therapy-on-post-fat-load-lipid-levels-in-patients-with-familial-dysbetalipoproteinemia-a-randomized-placebo-controlled-crossover-trial
#17
Charlotte Koopal, A David Marais, Jan Westerink, Yolanda van der Graaf, Frank L J Visseren
Familial dysbetalipoproteinemia (FD) is a genetic disorder associated with impaired postprandial lipid clearance. The effect of adding bezafibrate to standard lipid-lowering therapy on postprandial and fasting lipid levels in patients with FD is unknown. In this randomized placebo-controlled double-blind crossover trial, 15 patients with FD received bezafibrate and placebo for 6 weeks in randomized order in addition to standard lipid-lowering therapy (statin, ezetimibe, and/or lifestyle). We assessed post-fat load lipids, expressed as incremental area under the curve (iAUC) and area under the curve (AUC), as well as fasting levels and safety, and found that adding bezafibrate did not reduce post-fat load non-HDL-cholesterol (non-HDL-C) iAUC (1...
November 2017: Journal of Lipid Research
https://www.readbyqxmd.com/read/28916403/a-case-of-severe-acquired-hypertriglyceridemia-in-a-7-year-old-girl
#18
Jessica S Lilley, MacRae F Linton, Jennifer C Kelley, T Brent Graham, Sergio Fazio, Hagai Tavori
We report a case of severe type I hyperlipoproteinemia caused by autoimmunity against lipoprotein lipase (LPL) in the context of presymptomatic Sjögren's syndrome. A 7-year-old mixed race (Caucasian/African American) girl was admitted to the intensive care unit at Vanderbilt Children's Hospital with acute pancreatitis and shock. She was previously healthy aside from asthma and history of Hashimoto's thyroiditis. Admission triglycerides (TGs) were 2191 mg/dL but returned to normal during the hospital stay and in the absence of food intake...
August 12, 2017: Journal of Clinical Lipidology
https://www.readbyqxmd.com/read/28911687/simultaneous-separation-of-antihyperlipidemic-drugs-by-green-ultrahigh-performance-liquid-chromatography-diode-array-detector-method-improving-the-health-of-liquid-chromatography
#19
Mansoor Alghazi, Fars Alanazi, Kazi Mohsin, Nasir Ali Siddiqui, Faiyaz Shakeel, Nazrul Haq
Statins in combination with fibrates show beneficial effects on the lipoprotein profile of patients because they have positive complimentary effects on lipid profile. A new green ultrahigh-performance liquid chromatography-diode array detector method for simultaneous analysis of simvastatin (SMV) and fenofibrate (FNF) in standard form, marketed formulations, and self-emulsifying drug delivery system formulations was developed and validated in the present investigation. The method utilized C18 as stationary phase and a combination of methanol:water (8:2) as an eluent...
April 2017: Journal of Food and Drug Analysis
https://www.readbyqxmd.com/read/28866026/the-peroxisome-proliferator-activated-receptor-pan-agonist-bezafibrate-suppresses-microvascular-inflammatory-responses-of-retinal-endothelial-cells-and-vascular-endothelial-growth-factor-production-in-retinal-pigmented-epithelial-cells
#20
Ayumi Usui-Ouchi, Yasuo Ouchi, Nobuyuki Ebihara
A randomized clinical trial showed the beneficial effects of the selective peroxisome proliferator-activated receptor (PPAR)-α agonist, fenofibrate, in reducing the progression of diabetic retinopathy independent of serum lipid levels. All subtypes of PPAR (PPAR-α, PPAR-γ, and PPAR-β/δ) have been reported to play a key role in microvascular inflammation and angiogenesis. Therefore, the agonistic function of fenofibrate against the PPAR-α has been suggested to contribute to its medicinal effect. Furthermore, bezafibrate is a fibrate drug commonly used as a lipid-lowering agent to treat hyperlipidemia and acts as a pan-agonist of all PPARs subtypes...
November 2017: International Immunopharmacology
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