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HMG-CoA reductase

Miloš Skřivan, Milan Marounek, Michaela Englmaierová, Ladislav Čermák, Jana Vlčková, Eva Skřivanová
A group of 240-day-old Ross cockerels were used in a 4-week experiment to assess the effect of the fat type on the intestinal digestibility of fatty acids (FAs), the FA profiles of breast meat and abdominal fat, and the mRNA expression of six hepatic lipid-related genes. Experimental diets were supplemented with rapeseed oil, pork lard or palm oil at 60 g/kg. In the control diet, wheat starch was substituted for the fat source. The highest ileal digestibility of the fat and all FAs (except stearic acid) was observed in chickens fed lard...
2018: PloS One
Ryan K Dare, Chad Tewell, Bryan Harris, Patty W Wright, Sara L Van Driest, Eric Farber-Eger, George E Nelson, Thomas R Talbot
Background: Daptomycin-associated myopathy has been identified in 2-14% of patients, and rhabdomyolysis is a known adverse effect. Although risk factors for daptomycin-associated myopathy are poorly defined, creatine phosphokinase (CPK) monitoring and temporary discontinuation of HMG-CoA reductase inhibitors, or "statins", has been recommended. Methods: We conducted a single-center, retrospective, matched case-control risk factor analysis in adult and pediatric patients from 2004-2015...
April 16, 2018: Clinical Infectious Diseases: An Official Publication of the Infectious Diseases Society of America
Dominic Mitchell, Jason R Guertin, Anick Dubois, Marie-Pierre Dubé, Jean-Claude Tardif, Ange Christelle Iliza, Fiorella Fanton-Aita, Alexis Matteau, Jacques LeLorier
BACKGROUND: Statin (HMG-CoA reductase inhibitor) therapy is the mainstay dyslipidemia treatment and reduces the risk of a cardiovascular (CV) event (CVE) by up to 35%. However, adherence to statin therapy is poor. One reason patients discontinue statin therapy is musculoskeletal pain and the associated risk of rhabdomyolysis. Research is ongoing to develop a pharmacogenomics (PGx) test for statin-induced myopathy as an alternative to the current diagnosis method, which relies on creatine kinase levels...
April 12, 2018: Molecular Diagnosis & Therapy
Saleha Sadeeqa, Mariam Maqsood, Maqsood Ahmad
Cardiovascular diseases are considered to be the leading cause of disability and deaths in the whole world. The major cause behind this disease is the formation of lipid plagues in the form of thrombus. The statins (HMG-CoA reductase inhibitors) are used for the treatment and prevention of hyperlipidemia. Myopathy is the major side effect caused by statins. The purpose of this study was to determine the prevalence of statin induced myopathy. A cross-sectional study design was adopted using convenient random sampling technique at Punjab Institute of Cardiology, Lahore Pakistan from November 2016 to February 2017...
March 2018: Pakistan Journal of Pharmaceutical Sciences
Yu-An Chen, Ying-Ju Lin, Cheng-Li Lin, Hwai-Jeng Lin, Hua-Shan Wu, Hui-Ying Hsu, Yu-Chen Sun, Hui-Yu Wu, Chih-Ho Lai, Chia-Hung Kao
Prostate cancer (PCa) is one of the most commonly diagnosed cancers in the western world, and the mortality rate from PCa in Asia has been increasing recently. Statins are potent inhibitors of 3-hydroxy-3-methyl glutaryl coenzyme A (HMG-CoA) reductase and are commonly used for treating hyperlipidemia, with beneficial effects for cardiovascular disease and they also exhibit anti-cancer activity. However, the protective effects of statins against PCa are controversial. In this study, we investigated the effect of two types of statins (simvastatin and lovastatin) and the mortality rate of PCa patients by using the Taiwan National Health Insurance Research Database (NHIRD)...
2018: Frontiers in Pharmacology
Olga Oks, Shany Lewin, Irina Langier Goncalves, Amir Sapir
The mevalonate pathway is the primary target of the cholesterol-lowering drugs statins, some of the most widely prescribed medicines of all time. The pathway's enzymes not only catalyze the synthesis of cholesterol but also of diverse metabolites such as mitochondrial electron carriers and isoprenyls. Recently, it has been shown that one type of mitochondrial stress response, the UPRmt , can protect yeast, C. elegans, and cultured human cells from the deleterious effects of mevalonate pathway inhibition by statins...
March 29, 2018: Genetics
Amir A Zeki, Mona Elbadawi-Sidhu
Asthma manifests as chronic airflow obstruction with persistent inflammation and airway hyperresponsiveness. The immunomodulatory and anti-inflammatory properties of the HMG-CoA reductase (HMGCR) inhibitors (a.k.a. statins), suggest a therapeutic role in chronic inflammatory lung diseases. However, despite positive laboratory investigations and promising epidemiological data, clinical trials using statins for the treatment of asthma have yielded conflicting results. Inadequate statin levels in the airway compartment could explain these findings...
March 26, 2018: Expert Review of Respiratory Medicine
Yasin Ahmadi, Amir Ghorbanihaghjo, Mohsen Naghi-Zadeh, Neda Lotfi Yagin
Statins, inhibitors of hydroxy methyl glutaryl coenzyme-A (HMG-CoA) reductase, are the most widely used drugs for treating hypercholesterolemia. However, statins can cause disabling myopathy as their main adverse effect. Several molecular mechanisms underlie the statin-induced myopathy including the decrease in the levels of essential mevalonate and cholesterol derivatives. This review discusses a further mechanism involving the loss of other anti-oxidant defenses besides ubiquinone (Co-Q) in skeletal muscles which produce a significant amount of reactive oxygen species (ROS)...
March 24, 2018: Inflammopharmacology
Liu-Jing Wei, Suryang Kwak, Jing-Jing Liu, Stephan Lane, Qiang Hua, Dae-Hyuk Kweon, Yong-Su Jin
Squalene, a valuable acyclic triterpene, can be used as a chemical commodity for pharmacology, flavor, and biofuel industries. Microbial production of squalene has been of great interest due to its limited availability, and increasing prices extracted from animal and plant tissues. Here we report genetic perturbations that synergistically improve squalene production in Saccharomyces cerevisiae. As reported previously, overexpression of a truncated HMG-CoA reductase 1 (tHMG1) led to the accumulation 20-fold higher squalene than a parental strain...
March 24, 2018: Biotechnology and Bioengineering
Tulsankar Sachin Laxman, Santosh Puttervu, Anjali Mishra, Sarvesh Verma, S P Singh, K V Sashidhara, C M Marandi, Shivani Saxena, Manoj K Yadav, Rabi S Bhatta
1) 16α-hydroxycleroda-3, 13(14) Z -dien-15, 16-olide (4655K-09 or K-09) is a novel clerodane diterpene lactone reported for its anti hyperlipidemic efficacy. The objective of the present study was to investigate the probable reversible metabolism of 4655K-09 and evaluate its effects on pharmacokinetic (PK) properties. 2) The PK studies were carried out through intravenous (IV) bolus administration of 4655K-09 and K-9T in mice at a dose of 3, 6, and 12 mg/kg separately. The oral PK study of 4655K-09 were carried out at therapeutic dose of 25 mg/kg...
March 22, 2018: Xenobiotica; the Fate of Foreign Compounds in Biological Systems
Hsin-Hua Li, Chih-Li Lin, Chien-Ning Huang
A growing body of evidence suggests that disruption of the homeostasis of lipid metabolism affects the pathogenesis of Alzheimer's disease (AD). In particular, dysregulation of cholesterol homeostasis in the brain has been reported to considerably increase the risk of developing AD. Thus, dysregulation of lipid homeostasis may increase the amyloid β (Aβ) levels by affecting amyloid precursor protein (APP) cleavage, which is the most important risk factor involved in the pathogenesis of AD. Previous research demonstrated that Aβ can trigger neuronal insulin resistance, which plays an important role in response to Aβ-induced neurotoxicity in AD...
February 2018: Neural Regeneration Research
Kalaivani A, V V Sathibabu Uddandrao, Brahmanaidu Parim, Saravanan Ganapathy, Nivedha P R, Sushma Chandulee Kancharla, Rameshreddy P, Swapna K, Vadivukkarasi Sasikumar
In this study, we evaluated the ameliorative potential of Cucurbita maxima seeds oil (CSO (100 mg/kg body weight)) supplementation to high fat diet (HFD)-induced obese rats for 30 days on the changes in body weight, markers of lipid metabolism such as LDL, HDL, triglycerides, total cholesterol, adiponectin, leptin, amylase, and lipase. We also investigated the effects of CSO on the changes of lipid metabolic enzymes such as fatty-acid synthase, acetyl CoA carboxylase, carnitine palmitoyl transferase-1, HMG CoA reductase, and inflammatory markers (TNF-α and IL-6)...
March 19, 2018: Archives of Physiology and Biochemistry
Dongxia Fu, Haibin Cui, Yunna Zhang
BACKGROUND/AIMS: Non-alcoholic fatty liver disease (NAFLD) is the most common cause of chronic liver disease. This study aims to investigate whether chloride channel 2 (ClC-2) is involved in high fat diet (HFD)-induced NAFLD and possible molecular mechanisms. METHODS: ClC-2 expression was liver-specifically downregulated using adeno-associated virus in C57BL/6 mice treated with a chow diet or HFD for 12 weeks. Peripheral blood and liver tissues were collected for biochemical and pathological estimation respectively...
March 10, 2018: Cellular Physiology and Biochemistry
Marilene Lopes Ângelo, Fernanda de Lima Moreira, André Luís Morais Ruela, Ana Laura Araújo Santos, Hérida Regina Nunes Salgado, Magali Benjamim de Araújo
Rosuvastatin calcium (ROS), ( Figure 1 ) belongs to the "statins" group, which is the 3-hydroxy-3-methylglutaryl coenzyme A (HMG-CoA) reductase inhibitor. This drug is indicated for dyslipidemias treatment and can help to decrease the level of "bad cholesterol" and can consequently reduce the development of atherosclerosis and the risk of heart diseases. ROS was developed by Astra-Zeneca and it was approved in 2003 by the FDA in the United States. In 2015, under the trade name Crestor®, it was the fourth largest selling drug in the United States with sales above $5 billion...
March 13, 2018: Critical Reviews in Analytical Chemistry
Masahiro Ueki, Ichiro Kobayashi, Shunichiro Takezaki, Yusuke Tozawa, Yuka Okura, Masafumi Yamada, Masataka Kuwana, Tadashi Ariga
OBJECTIVES: The aim of our study is to clarify the association of myositis-specific autoantibodies (MSAs) with clinical and laboratory features in Japanese patients with juvenile idiopathic inflammatory myopathies (JIIMs). METHODS: We retrospectively analyzed the frequency of MSAs and their association with clinical or laboratory findings in 25 Japanese patients with JIIMs in Hokkaido district. RESULTS: Eighteen of 25 patients (72%) were positive for MSAs; seven with anti-melanoma differentiation associated gene (MDA) 5 (28%), 5 with anti-transcriptional intermediary factor (TIF)-1γ (20%), 4 with anti-MJ/nuclear matrix protein (NXP)-2 (16%), 2 with anti-Jo-1 (8%), 1 with anti- HMG-CoA reductase, 1 with anti-signal recognition peptide (SRP) antibodies (4% each), including co-existence and transition of MSAs in one patient each...
March 13, 2018: Modern Rheumatology
Bastian Vögeli, Sylvain Engilberge, Eric Girard, François Riobé, Olivier Maury, Tobias J Erb, Seigo Shima, Tristan Wagner
Many reactions within a cell are thermodynamically unfavorable. To efficiently run some of those endergonic reactions, nature evolved intermediate-channeling enzyme complexes, in which the products of the first endergonic reactions are immediately consumed by the second exergonic reactions. Based on this concept, we studied how archaea overcome the unfavorable first reaction of isoprenoid biosynthesis-the condensation of two molecules of acetyl-CoA to acetoacetyl-CoA catalyzed by acetoacetyl-CoA thiolases (thiolases)...
March 12, 2018: Proceedings of the National Academy of Sciences of the United States of America
Zhaojun Shen, Saisai Li, Bo Sheng, Qi Shen, Lu-Zhe Sun, Haiyan Zhu, Xueqiong Zhu
BACKGROUND: Medical therapeutic options remain quite limited for uterine fibroids treatment. Statins, competitive inhibitors of 3-hydroxy-3-methylglutaryl-coenzyme A reductase, have anti-tumoral effects on multiple cancer types, however, little is known about their effects on uterine fibroids. METHODS: Initially, we conducted a retrospective study of 120 patients with uterine fibroids and hyperlipidemia from the Second Affiliated Hospital of Wenzhou Medical University...
March 9, 2018: Journal of Translational Medicine
A J McFarland, A K Davey, C M McDermott, G D Grant, J Lewohl, S Anoopkumar-Dukie
3-Hydroxy-3-methylglutaryl-coenzyme A (HMG-CoA) reductase inhibitors (statins) have been associated with conflicting effects within the central nervous system (CNS), with underlying mechanisms remaining unclear. Although differences between individual statins' CNS effects have been reported clinically, few studies to date have compared multiple statins' neuroprotective effects. This study aimed to compare six statins (atorvastatin, fluvastatin, pitavastatin, pravastatin, rosuvastatin, simvastatin; 0-100 μM) using an in vitro model of lipopolysaccharide (LPS)-induced neuroinflammation and subsequent neurodegeneration...
March 6, 2018: Toxicology and Applied Pharmacology
Yoshiko Horie, Hiroko Makihara, Kazumasa Horikawa, Fumika Takeshige, Ai Ibuki, Toshihiko Satake, Kazunori Yasumura, Jiro Maegawa, Hideaki Mitsui, Kenichi Ohashi, Tomoko Akase
Skin barrier function is often deficient in obese individuals, but the underlying molecular mechanisms remain unclear. This study investigated how skin structure and lipid metabolism, factors strongly associated with barrier function, differed among 50 Japanese women of greatly varying body mass index (BMI). Subjects receiving breast reconstruction surgery were chosen for analysis to obtain skin samples from the same site. The subjects were classified into two groups, control (BMI < 25 kg/m2) and obese (25 kg/m2 ≤ BMI < 35 kg/m2), according to standards in Japan...
2018: PloS One
Yinzi Yue, Shuai Yan, Huan Li, Yang Zong, Jin Yue, Li Zeng
BACKGROUND: Postoperative peritoneal adhesions are a momentousness complication after abdominal surgery. Although varied means have been used to prevent and treat adhesions, the effects have not been satisfactory. Fluvastatin, a HMG-CoA reductase inhibitors, exhibits a variety of pharmacological effects. Aim of this study was to evaluate the effect of fluvastatin on postoperative peritoneal adhesion formation. METHODS: Seventy-five male Wistar rats weighting 220-250g were randomly assigned equally to three groups...
February 26, 2018: Acta Chirurgica Belgica
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