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Hyperlipidemia treatment

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https://www.readbyqxmd.com/read/28304296/pcsk9-promotes-oxldl-induced-pc12-cell-apoptosis-through-the-bcl-2-bax-caspase-9-3-signaling-pathway
#1
Lu-Shan Liu, Xue-Qin Bai, Ya Gao, Qi Wu, Zhong Ren, Qing Li, Li-Hong Pan, Ni-Ya He, Juan Peng, Zhi-Han Tang
BACKGROUND: Hyperlipidemia is a risk factor for neurodegenerative diseases. Proprotein convertase subtilisin / Kexin type 9 (PCSK9) degrades hepatic low-density lipoprotein receptor (LDLR) to regulate lipid metabolism. It is unclear if PCSK9 plays a role in neurodegenerative diseases. OBJECTIVE: This study was designed to determine whether PCSK9 is crucial between hyperlipidemia and Alzheimer's disease. The interrelationship between PCSK9 and neuronal apoptosis was explored in PC12 cells in response to treatment with oxidized low-density lipoprotein (oxLDL)...
March 10, 2017: Journal of Alzheimer's Disease: JAD
https://www.readbyqxmd.com/read/28304227/lipid-reduction-variability-and-antidrug-antibody-formation-with-bococizumab
#2
Paul M Ridker, Jean-Claude Tardif, Pierre Amarenco, William Duggan, Robert J Glynn, J Wouter Jukema, John J P Kastelein, Albert M Kim, Wolfgang Koenig, Steven Nissen, James Revkin, Lynda M Rose, Raul D Santos, Pamela F Schwartz, Charles L Shear, Carla Yunis
Background Bococizumab, a humanized monoclonal antibody targeting proprotein convertase subtilisin-kexin type 9 (PCSK9), reduces levels of low-density lipoprotein (LDL) cholesterol. However, the variability and durability of this effect are uncertain. Methods We conducted six parallel, multinational lipid-lowering trials enrolling 4300 patients with hyperlipidemia who were randomly assigned to receive 150 mg of bococizumab or placebo subcutaneously every 2 weeks and who were followed for up to 12 months; 96% were receiving statin therapy at the time of enrollment...
March 17, 2017: New England Journal of Medicine
https://www.readbyqxmd.com/read/28299646/hyperlipidemia-alters-the-pharmacokinetics-of-posaconazole-and-vincristine-upon-co-administration-in-rats
#3
Hadeel A Khalil, Mohammed A W ElKhatib, Tarek S Belal, Ahmed F El-Yazbi, Dalia A Hamdy
OBJECTIVES: Co-administration of posaconazole (PSZ) and vincristine (VCR) in the treatment of patients with acute lymphoblastic leukemia increases the neurotoxicity of VCR. Our aim is to study the effect of increased lipoprotein levels on the pharmacokinetics of PSZ and VCR upon co-administration in rats. METHODS: Rats were assigned to three groups, normolipidemic (NL), intermediate hyperlipidemic (IHL), and extreme hyperlipidemic (HL) groups. All rats were administered PSZ orally followed by VCR intravenously 4 h later...
March 15, 2017: Drugs in R&D
https://www.readbyqxmd.com/read/28299339/cytoplasmic-localization-of-wt1-and-decrease-of-mirna-16-1-in-nephrotic-syndrome
#4
Pablo Zapata-Benavides, Mariela Arellano-Rodríguez, Juan José Bollain-Y-Goytia, Moisés Armides Franco-Molina, Gloria Azucena Rangel-Ochoa, Esperanza Avalos-Díaz, Rafael Herrera-Esparza, Cristina Rodríguez-Padilla
Nephrotic syndrome (NS) is a glomerular disease that is defined by the leakage of protein into the urine and is associated with hypoalbuminemia, hyperlipidemia, and edema. Steroid-resistant NS (SRNS) patients do not respond to treatment with corticosteroids and show decreased Wilms tumor 1 (WT1) expression in podocytes. Downregulation of WT1 has been shown to be affected by certain microRNAs (miRNAs). Twenty-one patients with idiopathic NS (68.75% were SSNS and 31.25% SRNS) and 10 healthy controls were enrolled in the study...
2017: BioMed Research International
https://www.readbyqxmd.com/read/28296591/hypolipidemic-and-antioxidant-effects-of-malus-toringoides-rehd-hughes-leaves-in-high-fat-diet-induced-hyperlipidemic-rats
#5
Shan Huang, Haifeng Liu, Ning Meng, Bin Li, Jule Wang
Malus toringoides (Rehd.) Hughes (MT) leaves are traditionally used as a medicine for treating or preventing cardiovascular disease in Tibet. In addition to the effect of this medicinal plant on thrombosis, we tested its effect on dyslipidemia in a hypolipidemic rat model. A total of 60 healthy Sprague-Dawley rats were randomly divided into six groups, as follows: normal control, model control, simvastatin groups, and MT low-, medium-, and high-dose groups. The normal controls were fed with a normal diet, whereas all other groups were fed with a high-fat diet...
March 2017: Journal of Medicinal Food
https://www.readbyqxmd.com/read/28292968/micu1-alleviates-diabetic-cardiomyopathy-through-mitochondrial-ca-2-dependent-antioxidant-response
#6
Lele Ji, Fengzhou Liu, Zhe Jing, Qichao Huang, Ya Zhao, Haiyan Cao, Jun Li, Chun Yin, Jinliang Xing, Fei Li
Diabetic cardiomyopathy is a major cause of mortality in diabetic patients, but specific strategies for prevention or treatment of diabetic cardiomyopathy have not been clarified yet. MICU1 is a key regulator of mitochondria Ca(2+) uptake, which plays important roles in regulating mitochondrial oxidative phosphorylation and redox balance. However, to date, the significance of MICU1 in diabetic hearts has never been investigated. Here, we demonstrated that MICU1 was downregulated in db/db mouse heart, which contributes to myocardial apoptosis in diabetes...
March 14, 2017: Diabetes
https://www.readbyqxmd.com/read/28291840/a-wild-type-mouse-based-model-for-the-regression-of-inflammation-in-atherosclerosis
#7
Michael Peled, Hitoo Nishi, Ada Weinstock, Tessa J Barrett, Felix Zhou, Alexandra Quezada, Edward A Fisher
Atherosclerosis can be induced by the injection of a gain-of-function mutant of proprotein convertase subtilisin/kexin type 9 (PCSK9)-encoding adeno-associated viral vector (AAVmPCSK9), avoiding the need for knockout mice models, such as low-density lipoprotein receptor deficient mice. As regression of atherosclerosis is a crucial therapeutic goal, we aimed to establish a regression model based on AAVmPCSK9, which will eliminate the need for germ-line genetic modifications. C57BL6/J mice were injected with AAVmPCSK9 and were fed with Western diet for 16 weeks, followed by reversal of hyperlipidemia by a diet switch to chow and treatment with a microsomal triglyceride transfer protein inhibitor (MTPi)...
2017: PloS One
https://www.readbyqxmd.com/read/28289523/pcsk9-inhibitors-a-new-era-of-lipid-lowering-therapy
#8
REVIEW
Rahul Chaudhary, Jalaj Garg, Neeraj Shah, Andrew Sumner
Hyperlipidemia is a well-established risk factor for developing cardiovascular disease (CVD). The recent American College of Cardiology and American Heart Association guidelines on lipid management emphasize treatment of individuals at increased risk for developing CVD events with 3-hydroxy-3-methylglutaryl coenzyme A reductase inhibitors (statins) at doses proven to reduce CVD events. However, there are limited options for patients who are either intolerant to statin therapy, develop CVD despite being on maximally tolerated statin therapy, or have severe hypercholesterolemia...
February 26, 2017: World Journal of Cardiology
https://www.readbyqxmd.com/read/28283687/impact-of-gain-of-function-mutations-in-the-low-density-lipoprotein-receptor-related-protein-5-lrp5-on-glucose-and-lipid-homeostasis
#9
D Foer, M Zhu, R L Cardone, C Simpson, R Sullivan, S Nemiroff, G Lee, R G Kibbey, K F Petersen, K L Insogna
LRP5 loss-of-function mutations have been shown to cause profound osteoporosis and have been associated with impaired insulin sensitivity and dysregulated lipid metabolism. We hypothesized that gain-of-function mutations in LRP5 would also affect these parameters. We therefore studied individuals with LRP5 gain-of-function mutations exhibiting high bone mass (HBM) phenotypes and found that while there was no detected change in insulin sensitivity, there was a significant reduction in serum LDL. INTRODUCTION: Wnt signaling through LRP5 represents a newly appreciated metabolic pathway, which potentially represents a target for drug discovery in type 2 diabetes and hyperlipidemia...
March 10, 2017: Osteoporosis International
https://www.readbyqxmd.com/read/28276790/new-onset-diabetes-mellitus-induced-by-statins-current-evidence
#10
Steven G Chrysant
The hydroxyl-methyl-glutaryl-coenzyme-A (HMG-CoA) reductase inhibitors of statin action are very effective and safe drugs, and they are widely used for the treatment of hyperlipidemia and the prevention of primary and secondary cardiovascular diseases (CVDs). However, recent meta-analyses of previous studies done with statins have shown that these drugs could induce new onset diabetes mellitus (NODM), especially in subjects prone to diabetes: obese, females, older age, Asian descent, and those with pre-diabetes or the metabolic syndrome...
February 24, 2017: Postgraduate Medicine
https://www.readbyqxmd.com/read/28276256/lipid-lowering-treatment-modifications-among-patients-with-hyperlipidemia-and-a-prior-cardiovascular-event-a-us-retrospective-cohort-study
#11
Rajeshwari S Punekar, Kathleen M Fox, Carly J Paoli, Akshara Richhariya, Mark J Cziraky, Shravanthi R Gandra, Peter P Toth
BACKGROUND: Numerous studies demonstrate that, even with use of statins, many patients are unable to meet their LDL-C goals. This study examined modifications to statin and/or ezetimibe therapy among patients with hyperlipidemia and prior history of cardiovascular (CV) events in a US commercially insured population. METHODS: Adults (age ≥18 years) initiating statins and/or ezetimibe between 1 January 2007 and 31 December 2008 were identified from HealthCore Integrated Research Database...
March 9, 2017: Current Medical Research and Opinion
https://www.readbyqxmd.com/read/28274625/apd668-a-g-protein-coupled-receptor-119-agonist-improves-fat-tolerance-and-attenuates-fatty-liver-in-high-trans-fat-diet-induced-steatohepatitis-model-in-c57bl-6-mice
#12
Umakant Ashok Bahirat, Rekha Raghuveer Shenoy, Rajan Naresh Goel, Kumar V S Nemmani
G-protein coupled receptor 119 (GPR119) receptor is a rhodopsin-like, class A Gαs-coupled receptor, predominantly expressed in pancreatic islet cells and intestinal entero-endocrine cells. GPR119 has been emerged as a novel therapeutic target for the treatment of dyslipidemia in type 2 diabetes. In this study, we investigated the effect of APD668, a GPR119 agonist alone and in combination with linagliptin, a DPPIV inhibitor on oral fat tolerance test. Our findings demonstrate that APD668, a GPR119 agonist inhibits the intestinal triglyceride absorption after acute fat load in mice...
March 6, 2017: European Journal of Pharmacology
https://www.readbyqxmd.com/read/28272459/enoblock-a-unique-small-molecule-inhibitor-of-the-non-glycolytic-functions-of-enolase-alleviates-the-symptoms-of-type-2-diabetes
#13
Haaglim Cho, JungIn Um, Ji-Hyung Lee, Woong-Hee Kim, Wan Seok Kang, So Hun Kim, Hyung-Ho Ha, Yong-Chul Kim, Young-Keun Ahn, Da-Woon Jung, Darren R Williams
Type 2 diabetes mellitus (T2DM) significantly impacts on human health and patient numbers are predicted to rise. Discovering novel drugs and targets for treating T2DM is a research priority. In this study, we investigated targeting of the glycolysis enzyme, enolase, using the small molecule ENOblock, which binds enolase and modulates its non-glycolytic 'moonlighting' functions. In insulin-responsive cells ENOblock induced enolase nuclear translocation, where this enzyme acts as a transcriptional repressor. In a mammalian model of T2DM, ENOblock treatment reduced hyperglycemia and hyperlipidemia...
March 8, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28270893/association-of-whole-blood-viscosity-with-metabolic-syndrome-in-type-2-diabetic-patients-independent-association-with-post-breakfast-triglyceridemia
#14
Satomi Minato, Akiko Takenouchi, Junko Uchida, Ayaka Tsuboi, Miki Kurata, Keisuke Fukuo, Tsutomu Kazumi
BACKGROUND: Associations of whole blood viscosity (WBV) with metabolic syndrome (MS) have not been extensively studied in patients with type 2 diabetes. METHODS: Intrapersonal means of 12 measurements of waist circumference, blood pressure (BP) and high-density lipoprotein cholesterol and those of six measurements of fasting and post-breakfast triglycerides (TG) during 12 months were calculated in a cohort of 168 patients with type 2 diabetes. Based on these means, MS was diagnosed according to the modified National Cholesterol Education Program Adult Treatment Panel III criteria with the Asian definition of abdominal obesity...
April 2017: Journal of Clinical Medicine Research
https://www.readbyqxmd.com/read/28262618/2-4-chlorobenzyl-amino-4-methyl-1-3-thiazole-5-carboxylic-acid-exhibits-antidiabetic-potential-and-raises-insulin-sensitivity-via-amelioration-of-oxidative-enzymes-and-inflammatory-cytokines-in-streptozotocin-induced-diabetic-rats
#15
Yam Nath Paudel, Md Rahmat Ali, Sadia Shah, Mohd Adil, Md Sayeed Akhtar, Ravisha Wadhwa, Sandhya Bawa, Manju Sharma
Thiazole derivatives are potential candidates for drug development. They can be efficiently synthesized and are extremely active against several diseases, including diabetes. In our present study, we investigated the anti-diabetic, anti-oxidant and anti-inflammatory properties of 2-[(4-Chlorobenzyl) amino]-4-methyl-1,3-thiazole-5-carboxylic acid (BAC) a new thiazole derivative, in a streptozotocin (STZ) induced neonatal model of non-insulin dependent diabetes mellitus (NIDDM) rats. Diabetes was induced by injecting STZ (100mg/kg) intraperitoneally to two days old pups...
March 2, 2017: Biomedicine & Pharmacotherapy, Biomédecine & Pharmacothérapie
https://www.readbyqxmd.com/read/28261976/prevalence-of-co-morbidities-and-evaluation-of-their-monitoring-in-korean-patients-with-rheumatoid-arthritis-comparison-with-the-results-of-an-international-cross-sectional-study-comora
#16
In Ah Choi, Sung Hwan Park, Hoon-Suk Cha, Won Park, Hyun Ah Kim, Dae-Hyun Yoo, Han Joo Baek, Seong Geun Lee, Yoon Jong Lee, Yong Bum Park, Seung-Cheol Shim, Ihsane Hmamouchi, Yeong Wook Song
AIM: We designed this study to evaluate the prevalence of comorbidities, their monitoring states and association with treatment medication in Korean rheumatoid arthritis (RA) patients compared with patients from other countries. METHODS: We analyzed 1050 RA patients from 11 Korean centers and compared them with 3520 patients from 16 other countries using an international, cross-sectional study evaluating comorbidities of RA (COMORA) database. RESULTS: Annual evaluations of cardiovascular (CV) risk were less frequently performed in Korea (P = 0...
March 6, 2017: International Journal of Rheumatic Diseases
https://www.readbyqxmd.com/read/28258307/nutrition-for-diabetic-retinopathy-plummeting-the-inevitable-threat-of-diabetic-vision-loss
#17
REVIEW
Yashodhara Sharma, Sandeep Saxena, Arvind Mishra, Anita Saxena, Shankar Madhav Natu
Diabetic retinopathy (DR) is among the leading causes of preventable blindness. Hyperglycemia, hypertension, hyperlipidemia and anemia majorly predispose its pathogenesis. The current treatment modalities of DR include laser photocoagulation therapy, intravitreal corticosteroids, intravitreal anti-vascular endothelial growth factor (VEGF) agents and vitreo-retinal surgery which are costly, highly invasive, unproven for prolonged use and opted in advanced stages of DR. By then retina already encounters a vast damage...
March 3, 2017: European Journal of Nutrition
https://www.readbyqxmd.com/read/28247148/very-long-chain-acyl-coa-dehydrogenase-vlcad-deficiency-studies-on-treatment-effects-and-long-term-outcomes-in-mouse-models
#18
REVIEW
Sara Tucci
Very-long-chain-acyl-CoA-dehydrogenase deficiency is the most common disorder of mitochondrial long-chain fatty acid (LCFA) oxidation, with an incidence of 1:50,000-1:100,000 in newborns. Catabolic situations contribute to the aggravation of symptoms and induce severe metabolic derangement. Treatment for VLCAD-deficiency includes avoidance of fasting and a long-chain fat-restricted and fat-modified diet in which LCFAs are fully or partially replaced by medium-chain triglycerides (MCT). The aim of this work was to investigate the outcome and the effects of long-term treatment in a mouse model of VLCAD-deficiency...
February 28, 2017: Journal of Inherited Metabolic Disease
https://www.readbyqxmd.com/read/28246653/diabetes-obesity-and-other-medical-diseases-is-surgery-the-answer
#19
Dieter Pohl, Aaron Bloomenthal
For many physicians, the concept of surgery as the best treatment for a medical disease such as diabetes, cardiovascular problems, hyperlipidemia, sleep apnea, hepatosteatosis, GERD, osteoarthritis, psoriasis, rheumatoid arthritis, or infertility, still sounds wrong and just a ploy by surgeons to increase their business. Since 2011, however, several non-surgical societies have recommended Weight Loss Surgery - The International Diabetes Federation, The American Diabetes Association, American Heart Association, and Obesity Society in 2015 for patients with body mass index (BMI) greater than 35 and diabetes, and to decrease cardiovascular risk factors...
March 1, 2017: Rhode Island Medical Journal
https://www.readbyqxmd.com/read/28242176/2017-taiwan-lipid-guidelines-for-high-risk-patients
#20
REVIEW
Yi-Heng Li, Kwo-Chang Ueng, Jiann-Shing Jeng, Min-Ji Charng, Tsung-Hsien Lin, Kuo-Liong Chien, Chih-Yuan Wang, Ting-Hsing Chao, Ping-Yen Liu, Cheng-Huang Su, Shih-Chieh Chien, Chia-Wei Liou, Sung-Chun Tang, Chun-Chuan Lee, Tse-Ya Yu, Jaw-Wen Chen, Chau-Chung Wu, Hung-I Yeh
In Taiwan, the prevalence of hyperlipidemia increased due to lifestyle and dietary habit changes. Low density lipoprotein cholesterol (LDL-C) and non-high density lipoprotein cholesterol (non-HDL-C) are all significant predicting factors of coronary artery disease in Taiwan. We recognized that lipid control is especially important in patients with existed atherosclerotic cardiovascular diseases (ASCVD), including coronary artery disease (CAD), ischemic stroke and peripheral arterial disease (PAD). Because the risk of ASCVD is high in patients with diabetes mellitus (DM), chronic kidney disease (CKD) and familial hypercholesterolemia (FH), lipid control is also necessary in these patients...
February 24, 2017: Journal of the Formosan Medical Association, Taiwan Yi Zhi
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