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https://www.readbyqxmd.com/read/28842958/enhanced-diastereoselective-synthesis-of-t-butyl-6-cyano-3r-5r-dihydroxyhexanoate-by-using-aldo-keto-reductase-and-glucose-dehydrogenase-co-producing-engineered-escherichia-coli
#1
Ya-Jun Wang, Wei Shen, Xi Luo, Zhi-Qiang Liu, Yu-Guo Zheng
t-Butyl 6-cyano-(3R,5R)-dihydroxyhexanoate ((3R,5R)-2) is a key chiral diol precursor of atorvastatin calcium (Lipitor®). We have constructed a Kluyveromyces lactis aldo-keto reductase mutant KlAKR-Y295W/W296L (KlAKRm) by rational design in previous research, which displayed high activity and excellent diastereoselectivity (dep  > 99.5%) toward t-butyl 6-cyano-(5R)-hydroxy-3-oxohexanoate ((5R)-1). To realize in situ cofactor regeneration, a robust KlAKRm and Exiguobacterium sibiricum glucose dehydrogenase (EsGDH) co-producer E...
August 26, 2017: Biotechnology Progress
https://www.readbyqxmd.com/read/28817295/does-the-offer-of-free-prescriptions-increase-generic-prescribing
#2
Bruce Stuart, Franklin Hendrick, J Samantha Dougherty, Jing Xu
OBJECTIVES: To test if offering zero generic co-pays for oral antidiabetic drugs (OADs) and statins increases generic dispensing for low-income subsidy (LIS) recipients with diabetes enrolled in Medicare Part D. STUDY DESIGN: We analyzed a natural experiment in which LIS recipients were randomized to Part D plans in 2008. Some plans placed selected generic OADs and statins on zero co-pay tiers whereas others did not. Randomization eliminated selection effects which could bias the study findings...
June 1, 2017: American Journal of Managed Care
https://www.readbyqxmd.com/read/28814835/efficacy-and-tolerability-of-two-different-formulations-of-atorvastatin-in-korean-patients-with-hypercholesterolemia-a-multicenter-prospective-randomized-clinical-trial
#3
Ju-Hee Lee, Sang-Hyun Kim, Dong-Ju Choi, Seung-Jea Tahk, Jung-Han Yoon, Si Wan Choi, Taek-Jong Hong, Hyo-Soo Kim
PURPOSE: This study was designed to compare the efficacy and tolerability of the generic formulation (Atorva(®)) and the reference formulation (Lipitor(®)) of atorvastatin, both at a dosage of 20 mg once daily. METHODS: This study was a prospective open-label, randomized controlled study. Hypercholesterolemic patients who had not achieved low-density lipoprotein (LDL) cholesterol goals according to the National Cholesterol Education Program Adult Treatment Panel III (NCEP-ATP III) guideline were randomized to generic formulation or reference formulation of atorvastatin...
2017: Drug Design, Development and Therapy
https://www.readbyqxmd.com/read/28716156/generic-atorvastatin-is-as-effective-as-the-brand-name-drug-lipitor-%C3%A2-in-lowering-cholesterol-levels-a-cross-sectional-retrospective-cohort-study
#4
Alexander Loch, Jan Philipp Bewersdorf, Daniel Kofink, Dzafir Ismail, Imran Zainal Abidin, Ramesh Singh Veriah
BACKGROUND: In a world of ever increasing health care costs, generic drugs represent a major opportunity to ensure access to essential medicines for people who otherwise would be unable to afford them. However, some clinicians and patients are still questioning the safety and effectiveness of generic formulations compared to the proprietary drugs necessitating further systematic research analyzing the generic drugs' efficacy. Our objective was to compare the lipid lowering effects of generic and branded atorvastatin...
July 17, 2017: BMC Research Notes
https://www.readbyqxmd.com/read/28682888/spontaneous-recanalization-of-atherosclerotic-middle-cerebral-artery-occlusion-case-report
#5
Ying Mao, Yujing Huang, Li Zhang, Guangxian Nan
RATIONALE: Intracranial vascular atherosclerotic occlusion is one of the most common causes of ischemic stroke world wide. The involvement of large intracranial vessels, in particular, the middle cerebral artery, is usually associated with unfavorable outcomes in patients. Spontaneous recanalization of atherosclerotic occlusion is relatively rare. PATIENT CONCERNS: The first patient was a 43-year-old male with slurred speech and left-sided weakness for a duration of 24 hours...
July 2017: Medicine (Baltimore)
https://www.readbyqxmd.com/read/28644038/critical-review-on-the-analytical-techniques-for-the-determination-of-the-oldest-statin-atorvastatin-in-bulk-pharmaceutical-formulations-and-biological-fluids
#6
K S Kokilambigai, R Seetharaman, K S Lakshmi
Statins are a group of medicines that can help to lower the level of low-density-lipoprotein(LDL) cholesterol "bad cholesterol" in the blood. Having a high level of LDL cholesterol is potentially dangerous, as it can lead to a hardening and narrowing of arteries (atherosclerosis) and cardiovascular disease (CVD), Atorvastatin is one of the oldest member of the statin family and is used in the treatment of dyslipidemia and the prevention of cardiovascular disease. Atorvastatin was first made in August 1985 and from 1996 to 2012 under the trade name Lipitor, atorvastatin became the world's best selling drug...
June 23, 2017: Critical Reviews in Analytical Chemistry
https://www.readbyqxmd.com/read/28617150/atorvastatin-loaded-nanostructured-lipid-carriers-nlcs-strategy-to-overcome-oral-delivery-drawbacks
#7
Mohammed Elmowafy, Hany M Ibrahim, Mohammed A Ahmed, Khaled Shalaby, Ayman Salama, Hossam Hefesha
Atorvastatin (AT) is a widely used lipid-regulating drug to reduce cholesterol and triglycerides. Its poor aqueous solubility and hepatic metabolism require development of drug delivery systems able to improve its solubility and bypass hepatic effect. For this purpose, atorvastatin nanostructured lipid carriers (AT-NLCs) were prepared and characterized. AT-NLCs were prepared by emulsification using high-speed homogenization followed by ultrasonication. The prepared NLCs showed particle size between 162.5 ± 12 and 865...
November 2017: Drug Delivery
https://www.readbyqxmd.com/read/28559659/shen-yuan-dan-capsule-inhibiting-inflammatory-reaction-by-regulating-insulin-receptor-substrate-1-pi3k-akt-nf-%C3%AE%C2%BAb-signaling-pathway-in-apoliprotein-e-knockout-mice-fed-with-a-high-fat-diet
#8
Mingxue Zhou, Ping Li, Qunfu Kang, Lei Zhang, Juju Shang, Weihong Liu, Hongxu Liu
BACKGROUND: Shen-Yuan-Dan Capsule (SYDC), a traditional Chinese medicine, is proposed to have the capacity to prevent angina pectoris. However, the effects and the related mechanisms of SYDC on atherosclerosis (AS) are still unknown. This study was designed to investigate the effects of SYDC on AS and inflammatory reaction in the apoliprotein E-knockout (ApoE(-/-)) mice fed with a high-fat diet. METHODS: Thirty eight-week-old male ApoE(-/-) mice were randomly divided into three groups (n = 10) 6 weeks after being fed with a high-fat diet: the control group, the lipitor group, and the SYDC group...
May 2017: Acta Cardiologica Sinica
https://www.readbyqxmd.com/read/28491104/effect-of-tetramethylpyrazine-on-atherosclerosis-and-scap-srebp-1c-signaling-pathway-in-apoe-mice-fed-with-a-high-fat-diet
#9
Ying Zhang, Pan Ren, Qunfu Kang, Weihong Liu, Sinai Li, Ping Li, Hongxu Liu, Juju Shang, Lei Zhang, Yanbing Gong, Mingxue Zhou
Lipid metabolism dysregulation plays a crucial role in the occurrence of atherosclerosis (As). SCAP/SREBP signaling is the main pathway for regulating lipid metabolism. Tetramethylpyrazine (TMP), a Traditional Chinese Medicine (TCM) for treating angina pectoris, has antiatherosclerotic effects and ameliorates blood lipids disturbance. However, its precise mechanism remains unclear. This study investigated the mechanism of TMP in ameliorating As in mice model. After six weeks of high-fat diet, 30 ApoE(-/-) mice were randomized (n = 10) and treated with Lipitor, TMP, or distilled water for six weeks...
2017: Evidence-based Complementary and Alternative Medicine: ECAM
https://www.readbyqxmd.com/read/28427921/enhancement-of-ethyl-s-4-chloro-3-hydroxybutanoate-production-at-high-substrate-concentration-by-in-situ-resin-adsorption
#10
Li-Feng Chen, Hai-Yang Fan, Yi-Ping Zhang, Wei Wei, Jin-Ping Lin, Dong-Zhi Wei, Hua-Lei Wang
Asymmetric reduction of ethyl 4-chloro-3-oxobutyrate (COBE) by carbonyl reductases presents an efficient way to produce Ethyl (S)-4-chloro-3-hydroxybutanoate ((S)-CHBE), an important chiral intermediate for the synthesis of hydroxymethylglutaryl-CoA reductase inhibitors such as Lipitor(®). In this study, an NADPH-dependent carbonyl reductase (SrCR) from Synechocystis sp. was characterized to demonstrate a broad substrate spectrum, and the highest activity (53.1U/mg protein) with COBE. To regenerate the cofactor NADPH, Bacillus subtilis glucose dehydrogenase was successfully coexpressed with SrCR...
April 17, 2017: Journal of Biotechnology
https://www.readbyqxmd.com/read/28418852/structural-homologies-between-phenformin-lipitor-and-gleevec-aim-the-same-metabolic-oncotarget-in-leukemia-and-melanoma
#11
REVIEW
Gábor Somlyai, T Que Collins, Emmanuelle J Meuillet, Patel Hitendra, Dominic P D'Agostino, László G Boros
Phenformin's recently demonstrated efficacy in melanoma and Gleevec's demonstrated anti-proliferative action in chronic myeloid leukemia may lie within these drugs' significant pharmacokinetics, pharmacodynamics and structural homologies, which are reviewed herein. Gleevec's success in turning a fatal leukemia into a manageable chronic disease has been trumpeted in medical, economic, political and social circles because it is considered the first successful targeted therapy. Investments have been immense in omics analyses and while in some cases they greatly helped the management of patients, in others targeted therapies failed to achieve clinically stable recurrence-free disease course or to substantially extend survival...
July 25, 2017: Oncotarget
https://www.readbyqxmd.com/read/28414942/coenzyme-q10-protects-against-statin-induced-myotoxicity-in-zebrafish-larvae-danio-rerio
#12
Rand Pasha, Thomas W Moon
3-Hydroxy-3-methylglutaryl-CoA reductase (HMGCR) is the rate-limiting enzyme of the mevalonic acid pathway and is required for cholesterol biosynthesis and the synthesis of Coenzyme Q10 (CoQ10). Statins inhibit HMGCR, thus inhibiting the downstream products of this pathway including the biosynthesis of decaprenyl-pyrophosphate that is critical for the synthesis of Coenzyme Q10 (CoQ10). We show that zebrafish (Danio rerio) larvae treated in tank water with Atorvastatin (ATV; Lipitor) exhibited movement alterations and reduced whole body tissue metabolism...
June 2017: Environmental Toxicology and Pharmacology
https://www.readbyqxmd.com/read/28389544/engineering-streptomyces-coelicolor-carbonyl-reductase-for-efficient-atorvastatin-precursor-synthesis
#13
Min Li, Zhi-Jun Zhang, Xu-Dong Kong, Hui-Lei Yu, Jiahai Zhou, Jian-He Xu
Streptomyces coelicolor CR1 (ScCR1) has been shown to be a promising biocatalyst for the synthesis of an atorvastatin precursor, ethyl-(S)-4-chloro-3-hydroxybutyrate [(S)-CHBE]. However, limitations of ScCR1 observed for practical application include low activity and poor stability. In this work, protein engineering was employed to improve the catalytic efficiency and stability of ScCR1. First, the crystal structure of ScCR1 complexed with NADH and cosubstrate 2-propanol was solved, and the specific activity of ScCR1 was increased from 38...
June 15, 2017: Applied and Environmental Microbiology
https://www.readbyqxmd.com/read/27659855/invalidation-of-atorvastatin-patent-highlights-complex-chinese-patent-law
#14
Feng-Chi Chen, Kuo-Liang Yeh
Pfizer's atorvastatin (Lipitor) is a blockbuster drug for the treatment of cardiovascular diseases. In China, a critical polymorph patent of this drug has been recently invalidated by the Supreme People's Court for insufficiency of disclosure. Here, we discuss the particularities in patent litigation in China worth attention from the community.
November 2016: Trends in Pharmacological Sciences
https://www.readbyqxmd.com/read/27601271/can-social-media-data-lead-to-earlier-detection-of-drug-related-adverse-events
#15
Mei Sheng Duh, Pierre Cremieux, Marc Van Audenrode, Francis Vekeman, Paul Karner, Haimin Zhang, Paul Greenberg
PURPOSE: To compare the patient characteristics and the inter-temporal reporting patterns of adverse events (AEs) for atorvastatin (Lipitor(®) ) and sibutramine (Meridia(®) ) in social media (AskaPatient.com) versus the FDA Adverse Event Reporting System (FAERS). METHODS: We identified clinically important AEs associated with atorvastatin (muscle pain) and sibutramine (cardiovascular AEs), compared their patterns in social media postings versus FAERS and used Granger causality tests to assess whether social media postings were useful in forecasting FAERS reports...
December 2016: Pharmacoepidemiology and Drug Safety
https://www.readbyqxmd.com/read/27542158/simultaneous-bilateral-carotid-stenting-for-symptomatic-bilateral-high-grade-carotid-stenosis-a-retrospective-clinical-investigation
#16
Ziming Ye, Ying Liu, Xiao Deng, Xiangren Chen, Cuiting Lin, Yanyan Tang, Ying Su, Lanji Fang, Yuan Wu, Chao Qin
BACKGROUND This retrospective clinical investigation aimed to evaluate the short-term effectiveness and safety of SBCAS for symptomatic bilateral high-grade CS. MATERIAL AND METHODS From 2009 to 2014, 145 patients were recruited. Among them, 70 underwent SBCAS, and other 75 patients underwent SAMM and served as controls. The immediate postprocedural complications and postprocedural neurological evaluation, as well as restenosis at 6-month and 1-year follow-ups in the SBCAS group are reported. Additionally, baseline risk factors for ischemic stroke, adverse effects of drugs, and outcomes at 30-day, 6-month, and 1-year follow-ups were compared between the 2 groups...
August 19, 2016: Medical Science Monitor: International Medical Journal of Experimental and Clinical Research
https://www.readbyqxmd.com/read/27098970/comparative-effectiveness-of-generic-atorvastatin-and-lipitor%C3%A2-in-patients-hospitalized-with-an-acute-coronary-syndrome
#17
Cynthia A Jackevicius, Jack V Tu, Harlan M Krumholz, Peter C Austin, Joseph S Ross, Therese A Stukel, Maria Koh, Alice Chong, Dennis T Ko
BACKGROUND: Although generic medications are approved based on bioequivalence with brand-name medications, there remains substantial concern regarding their clinical effectiveness and safety. Lipitor(®), available as generic atorvastatin, is one of the most commonly prescribed statins. Therefore, we compared the effectiveness of generic atorvastatin products and Lipitor(®). METHODS AND RESULTS: We conducted a population-based cohort study, using propensity score matching to minimize potential confounding of patients ≥65 years, discharged alive after acute coronary syndrome (ACS) hospitalization between 2008 and 2012 in Ontario, Canada, who were prescribed Lipitor(®) or generic atorvastatin within 7 days of discharge...
April 19, 2016: Journal of the American Heart Association
https://www.readbyqxmd.com/read/27021467/pd-pk-evaluation-of-freeze-dried-atorvastatin-calcium-loaded-poly-%C3%AE%C2%B5-caprolactone-nanoparticles
#18
Iman S Ahmed, Rania El-Hosary, Samia Shalaby, Marwa M Abd-Rabo, Dalia G Elkhateeb, Samia Nour
In this work lyophilized poly-ε-caprolactone nanoparticles (NPs) loaded with atorvastatin calcium (AC) were developed in an attempt to improve the in-vivo performance of AC following oral administration. The individual and combined effects of several formulation variables were previously investigated using step-wise full factorial designs in order to produce optimized AC-NPs with predetermined characteristics including particle size, drug loading capacity, drug release profile and physical stability. Four optimized formulations were further subjected in this work to lyophilization to promote their long-term physical stability and were fully characterized...
May 17, 2016: International Journal of Pharmaceutics
https://www.readbyqxmd.com/read/26985922/therapeutic-effect-of-pleurotus-eryngii-cellulose-on-experimental-fatty-liver-in-rats
#19
J F Huang, T Zhan, X L Yu, Q A He, W J Huang, L Z Lin, Y T Du, Y T Pan
The aim of this study was to explore the therapeutic effect of Pleurotus eryngii cellulose on experimental fatty liver in rats. Rats were fed high-fat fodder to establish a rat fatty liver model, and were then fed different concentrations of Pleurotus eryngii cellulose for six weeks. Lipitor was used as a positive control. Measured levels of alanine aminotransferase (ALT), aspartate aminotransferase (AST), total cholesterol (TC), and total triglyceride (TG); the activity of malondialdehyde (MDA), superoxide dismutase (SOD), hepatic lipase (HL), and lipoprotein lipase; and liver histopathological changes...
February 26, 2016: Genetics and Molecular Research: GMR
https://www.readbyqxmd.com/read/26879926/atorvastatin-lipitor-attenuates-the-effects-of-aspirin-on-pancreatic-cancerogenesis-and-the-chemotherapeutic-efficacy-of-gemcitabine-on-pancreatic-cancer-by-promoting-m2-polarized-tumor-associated-macrophages
#20
Qiaofei Liu, Yuan Li, Zheyu Niu, Yi Zong, Mengyi Wang, Lutian Yao, Zhaohui Lu, Quan Liao, Yupei Zhao
BACKGROUND: Interactions of inflammatory cells with pancreatic cancer cells play crucial roles in pancreatic cancer, however the dynamic changes of inflammatory cell populations in pancreatic cancerogensis and after chemotherapy have not been well eclucidated. The combinational use of aspirin and atrovastatin (Lipitor) have been widely prescribled for cardio-cerebral vascular diseases mainly by regulation of inflammations, and they have been also reported to have plausible anti-tumor effects, however their potential roles in pancreatic cancerogenesis and chemotherapeutic effects have been seldom investigated...
February 16, 2016: Journal of Experimental & Clinical Cancer Research: CR
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