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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
Sonal Singh, Caitrin W McDonough, Yan Gong, Wael A Alghamdi, Meghan J Arwood, Salma A Bargal, Leanne Dumeny, Wen-Yi Li, Mai Mehanna, Bradley Stockard, Guang Yang, Felipe A de Oliveira, Natalie C Fredette, Mohamed H Shahin, Kent R Bailey, Amber L Beitelshees, Eric Boerwinkle, Arlene B Chapman, John G Gums, Stephen T Turner, Rhonda M Cooper-DeHoff, Julie A Johnson
BACKGROUND: Thiazide and thiazide-like diuretics are first-line medications for treating uncomplicated hypertension. However, their use has been associated with adverse metabolic events, including hyperglycemia and incident diabetes mellitus, with incompletely understood mechanisms. Our goal was to identify genomic variants associated with thiazide-like diuretic/chlorthalidone-induced glucose change. METHODS AND RESULTS: Genome-wide analysis of glucose change after treatment with chlorthalidone was performed by race among the white (n=175) and black (n=135) participants from the PEAR-2 (Pharmacogenomic Evaluation of Antihypertensive Responses-2)...
March 9, 2018: Journal of the American Heart Association
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
Quan-Zhen Lv, Yu-Lin Qin, Lan Yan, Liang Wang, Chuyue Zhang, Yuan-Ying Jiang
Antifungal azole drugs inhibit the synthesis of ergosterol and cause the accumulation of sterols containing a 14α-methyl group, which is related to the properties of cell membrane. Due to the frequent recurrence of fungal infections and clinical long-term prophylaxis, azole resistance is increasing rapidly. In our research, Nsg2p, encoded by the ORF19.273 in Candida albicans , is found to be involved in the inhibition of 14α-methylated sterols and resistance to azoles. Under the action of fluconazole, nsg2 Δ/Δ mutants are seriously damaged in the integrity and functions of cell membranes with a decrease of ergosterol ratio and an increase of both obtusifoliol and 14α-methylfecosterol ratio...
2018: Frontiers in Microbiology
Yohei Tatematsu, Haruhi Fujita, Hiroki Hayashi, Atsushi Yamamoto, Atsushi Tabata, Hideaki Nagamune, Kazuto Ohkura
Nonsteroidal anti-inflammatory drugs (NSAIDs) are widely used to treat inflammation and pain. In the present study, we examined the effects of celecoxib, a cyclooxygenase-2 (COX-2)-selective NSAID, on rat liver mitochondrial function. Celecoxib dose-dependently induced mitochondria swelling, which was not suppressed by cyclosporine A (CsA). The oxygen consumption rate in mitochondria-suspended solution was facilitated by the addition of celecoxib, and its uncoupling activity was observed. Celecoxib also suppressed SF6847-induced uncoupling, and appeared to exert inhibitory effects on the electron transport chain...
2018: Biological & Pharmaceutical Bulletin
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
Marc Foretz, Benoit Viollet
AMP-activated protein kinase (AMPK) is a master regulator of multiple cellular metabolic pathways, including lipid metabolism. Some of the well-known substrates of AMPK are acetyl-CoA carboxylase (ACC) and 3-hydroxy-3-methylglutaryl-coenzyme A (HMG-CoA) reductase, regulatory enzymes of fatty acid and cholesterol synthesis, respectively. The discovery that both of them are inactivated by AMPK suggested the therapeutic potential of AMPK activation in the treatment of metabolic diseases associated with lipid disorders, such as nonalcoholic fatty liver disease (NAFLD)...
2018: Methods in Molecular Biology
Shilpi Bansal, Lokesh Kumar Narnoliya, Bhawana Mishra, Muktesh Chandra, Ritesh Kumar Yadav, Neelam Singh Sangwan
Ocimum kilimandscharicum is unique in possessing terpenoids whereas other Ocimum species are renowned for phenylpropanoids as major constituents of essential oil. The key enzyme of MVA/terpenoid metabolic pathway viz 3-hydroxy-3-methylglutaryl Co-A reductase (OkHMGR) of 1.7-Kb ORF encoding ~60-kDa protein was cloned from O. kilimandscharicum and its kinetic characteristics revealed the availability of HMG-CoA as a control point of MVA-pathway. Transcript profiling of the OkHMGR elucidated tissue-specific functions of the gene in flower and leaf tissues in accumulation of terpenoidal essential oil...
February 23, 2018: Scientific Reports
Hyunah Kim, Hyeseon Lee, Tong Min Kim, So Jung Yang, Seo Yeon Baik, Seung-Hwan Lee, Jae-Hyoung Cho, Hyunyong Lee, Hyeon Woo Yim, In Young Choi, Kun-Ho Yoon, Hun-Sung Kim
AIM: Prescription of statins to patients with chronic liver disease whose alanine transaminase (ALT) is over three times the upper normal limit (UNL) is not recommended. In this study, we attempted to evaluate patients with baseline ALT levels > 3 × UNL who were prescribed statins without ethical problems, using electronic medical records. METHODS: We enrolled subjects with ALT levels > 3 × UNL. The patients were divided into three groups consisting of those who had been taking agents affecting liver function (HEPA) and continued to do so after the statin prescription (HepCon), those who had not previously taken HEPA and began doing so after statin prescription (HepNew), and those who had never taken HEPA (HepNo)...
February 21, 2018: Cardiovascular Therapeutics
Talles Prosperi de Paula, Patrícia Campi Santos, Raquel Duque do Nascimento Arifa, Angélica T Vieira, Ludmila de Matos Baltazar, Thiago Vinícius Ávila, Caio Tavares Fagundes, Zélia Menezes Garcia, Renata Lacerda Lima, Mauro Martins Teixeira, Danielle G Souza
The clinical pathogen Klebsiella pneumoniae is a relevant cause of nosocomial infections and resistance to current treatment with carbapenem antibiotics is becoming a significant problem. Statins are inhibitors of 3-hydroxy-3-methylglutaryl coenzyme A (HMG-CoA) used for controlling plasma cholesterol levels. There is clinical evidence showing other effects of statins, including decrease of lung inflammation. In the current study, we show that pretreatment with atorvastatin markedly attenuated lung injury, which was correlated with a reduction in the cellular influx into the alveolar space and lungs and down-modulation of the production of pro-inflammatory mediators in the initial phase of infection in C57BL/6 mice with K...
February 20, 2018: Antimicrobial Agents and Chemotherapy
Masayuki Hashiguchi, Junya Maruyama, Mikiko Shimizu, Daichi Takahashi, Tsuyoshi Shiga
To investigate whether 3-hydroxy-3-methylglutaryl-coenzyme A reductase inhibitor (statin) use is associated with an increased risk of diabetes mellitus and hyperglycemia, we performed a nested case-control study using a postmarketing surveillance database in Japan. The database cohort included 26,849 cases of statin use and 5308 cases of other lipid-lowering drug use in patients with hyperlipidemia. Participants received at least 1 type of statin, had a clear medication history of statin use, and had no complications of diabetes mellitus...
February 20, 2018: Clinical Pharmacology in Drug Development
QingQing Wang, Lili Guo, Cassandra J Strawser, Lauren A Hauser, Wei-Ting Hwang, Nathaniel W Snyder, David R Lynch, Clementina Mesaros, Ian A Blair
Friedreich's ataxia (FA) is an autosomal recessive neurodegenerative disorder, which results primarily from reduced expression of the mitochondrial protein frataxin. FA has an estimated prevalence of one in 50,000 in the population, making it the most common hereditary ataxia. Paradoxically, mortality arises most frequently from cardiomyopathy and cardiac failure rather than from neurological effects. Decreased high-density lipoprotein (HDL) and apolipoprotein A-I (ApoA-l) levels in the general population are associated with an increased risk of mortality from cardiomyopathy and heart failure...
2018: PloS One
Claus-Peter Richter, Hunter Young, Sonja V Richter, Virginia Smith-Bronstein, Stuart R Stock, Xianghui Xiao, Carmen Soriano, Donna S Whitlon
Exposure to noise and ototoxic drugs are responsible for much of the debilitating hearing loss experienced by about 350 million people worldwide. Beyond hearing aids and cochlear implants, there have been no other FDA approved drug interventions established in the clinic that would either protect or reverse the effects of hearing loss. Using Auditory Brainstem Responses (ABR) in a guinea pig model, we demonstrate that fluvastatin, an inhibitor of HMG-CoA reductase, the rate-limiting enzyme of the mevalonate pathway, protects against loss of cochlear function initiated by high intensity noise...
February 14, 2018: Scientific Reports
K Mladenovska, A Daka Grapci, M Vavlukis, A Kapedanovska, A Eftimov, N Matevska Geshkovska, D Nebija, A J Dimovski
Atorvastatin, as 3-hydroxy-3-methylglutaryl coenzyme A (HMG-CoA) reductase inhibitor, is a widely prescribed medication for the treatment of dyslipidemia. However, despite its clinical efficacy in reducing major cardiovascular events, a wide inter-individual variability in its response exists. Several studies in this area point to the effect of polymorphisms in the solute carrier organic anion transporter 1B1 (SLCO1B1) gene encoding the multiple organic anion-transporting polypeptide 1B1 (OATP1B1) involved in hepatic uptake of atorvastatin...
May 1, 2017: Die Pharmazie
Lijun Wang, Hanyue Zhu, Yimin Zhao, Rui Jiao, Lin Lei, Jingnan Chen, Xiaobo Wang, Zhengnan Zhang, Yu Huang, Tiejie Wang, Zhen-Yu Chen
BACKGROUND: Interest in using herbal medicines to treat the hypercholesterolemia is increasing. Cranberry extract could decrease plasma cholesterol, however, the active ingredients and the underlying mechanisms remain largely unknown. HYPOTHESIS: The present study was to test the hypothesis that cranberry anthocyanins (CrA) were at least one of the active ingredients responsible for the cholesterol-lowering activity of cranberry fruits via a mechanism of increasing fecal sterol excretion...
January 1, 2018: Phytomedicine: International Journal of Phytotherapy and Phytopharmacology
Tiphaine Birien, Axel Thiel, Ghislaine Henneke, Didier Flament, Yann Moalic, Mohamed Jebbar
A gene disruption system for Thermococcus barophilus was developed using simvastatin (HMG-CoA reductase encoding gene) for positive selection and 5-Fluoroorotic acid (5-FOA), a pyrF gene for negative selection. Multiple gene mutants were constructed with this system, which offers the possibility of complementation in trans, but produces many false positives (<80%). To significantly reduce the rate of false positives, we used another counterselective marker, 6-methylpurine (6-MP), a toxic analog of adenine developed in Thermococcus kodakarensis, consistently correlated with the TK0664 gene (encoding a hypoxanthine-guanine phosphoribosyl-transferase)...
February 7, 2018: Genes
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