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https://www.readbyqxmd.com/read/29204050/current-and-emerging-pharmacological-therapy-for-non-alcoholic-fatty-liver-disease
#1
EDITORIAL
Ahad Eshraghian
The main treatment of patients with non-alcoholic fatty liver disease (NAFLD) is life style modification including weight reduction and dietary regimen. Majority of patients are safely treated with this management and pharmacologic interventions are not recommended. However, a subgroup of NAFLD patients with non-alcoholic steatohepatitis (NASH) who cannot achieve goals of life style modification may need pharmacological therapy. One major obstacle is measurement of histological outcome by liver biopsy which is an invasive method and is not recommended routinely in these patients...
November 14, 2017: World Journal of Gastroenterology: WJG
https://www.readbyqxmd.com/read/29203092/efficacy-and-safety-of-pemafibrate-k-877-a%C3%A2-selective-peroxisome-proliferator-activated-receptor-%C3%AE-modulator-in-patients-with-dyslipidemia-results-from-a-24-week-randomized-double-blind-active-controlled-phase-3-trial
#2
Shun Ishibashi, Hidenori Arai, Koutaro Yokote, Eiichi Araki, Hideki Suganami, Shizuya Yamashita
BACKGROUND: To overcome the concerns associated with the use of fibrates, pemafibrate (K-877), a novel selective peroxisome proliferator-activated receptor modulator, was developed. In a previous phase 2 trial, we showed excellent efficacy and safety of pemafibrate in patients with dyslipidemia. OBJECTIVE: The objective of the study was to evaluate the efficacy and safety of pemafibrate over 24 weeks in adults with dyslipidemia in comparison with fenofibrate. METHODS: In this multicenter, 24-week, double-blind, clinical study, 225 patients with high triglyceride (TG; ≥150 mg/dL [1...
October 28, 2017: Journal of Clinical Lipidology
https://www.readbyqxmd.com/read/29183206/fibrates-in-the-management-of-atherogenic-dyslipidemia
#3
Bogusław Okopień, Lukasz Buldak, Aleksandra Bołdys
Significant advancements in the treatment of hypercholesterolemia have recently been achieved. However, a considerable level of residual cardiovascular risk still affects patients' outcomes. Atherogenic dyslipidemia is one of the major constituents of residual risk. Fibrates, PPAR alpha agonists, which modify lipid profile and have numerous pleiotropic effects, seem to be drugs of choice in patients with atherogenic dyslipidemia. These drugs are effective both in monotherapy and combined therapy with statins...
November 28, 2017: Expert Review of Cardiovascular Therapy
https://www.readbyqxmd.com/read/29182629/effects-of-peroxisome-proliferator-activated-receptors-ppar-%C3%AE-and-%C3%AE-agonists-on-cochlear-protection-from-oxidative-stress
#4
Marijana Sekulic-Jablanovic, Vesna Petkovic, Matthew B Wright, Krystsina Kucharava, Nathan Huerzeler, Soledad Levano, Yves Brand, Katharina Leitmeyer, Andrea Glutz, Alexander Bausch, Daniel Bodmer
Various insults cause ototoxicity in mammals by increasing oxidative stress leading to apoptosis of auditory hair cells (HCs). The thiazolidinediones (TZDs; e.g., pioglitazone) and fibrate (e.g., fenofibrate) drugs are used for the treatment of diabetes and dyslipidemia. These agents target the peroxisome proliferator-activated receptors, PPARγ and PPARα, which are transcription factors that influence glucose and lipid metabolism, inflammation, and organ protection. In this study, we explored the effects of pioglitazone and other PPAR agonists to prevent gentamicin-induced oxidative stress and apoptosis in mouse organ of Corti (OC) explants...
2017: PloS One
https://www.readbyqxmd.com/read/29176657/dyslipidaemia-in-nephrotic-syndrome-mechanisms-and-treatment
#5
REVIEW
Shipra Agrawal, Joshua J Zaritsky, Alessia Fornoni, William E Smoyer
Nephrotic syndrome is a highly prevalent disease that is associated with high morbidity despite notable advances in its treatment. Many of the complications of nephrotic syndrome, including the increased risk of atherosclerosis and thromboembolism, can be linked to dysregulated lipid metabolism and dyslipidaemia. These abnormalities include elevated plasma levels of cholesterol, triglycerides and the apolipoprotein B-containing lipoproteins VLDL and IDL; decreased lipoprotein lipase activity in the endothelium, muscle and adipose tissues; decreased hepatic lipase activity; and increased levels of the enzyme PCSK9...
November 27, 2017: Nature Reviews. Nephrology
https://www.readbyqxmd.com/read/29175453/activation-of-ppar%C3%AE-decreases-bile-acids-in-livers-of-female-mice-while-maintaining-bile-flow-and-biliary-bile-acid-excretion
#6
Youcai Zhang, Andrew J Lickteig, Iván L Csanaky, Curtis D Klaassen
Fibrates are hypolipidemic drugs that act as activators of peroxisome proliferator-activated receptor α (PPARα). In both humans and rodents, females were reported to be less responsive to fibrates than males. Previous studies on fibrates and PPARα usually involved male mice, but little has been done in females. The present study aimed to provide the first comprehensive analysis of the effects of clofibrate (CLOF) and PPARα on bile acid (BA) homeostasis in female mice. Study in WT male mice showed that a 4-day CLOF treatment increased liver weight, bile flow, and biliary BA excretion, but decreased total BAs in both serum and liver...
November 22, 2017: Toxicology and Applied Pharmacology
https://www.readbyqxmd.com/read/29155776/differential-effects-of-lipid-lowering-drugs-in-modulating-morphology-of-cholesterol-particles
#7
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
#8
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
#9
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
#10
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
#11
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
#12
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
#13
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
#14
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
#15
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
#16
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
#17
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
#18
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
#19
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...
December 2017: Current Opinion in Lipidology
https://www.readbyqxmd.com/read/28952474/-pitavastatin-tolerability-and-advers-effect-profile
#20
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
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