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https://www.readbyqxmd.com/read/28092275/mechanistic-insights-from-combining-genomics-with-metabolomics
#1
Fotios Drenos
PURPOSE OF REVIEW: Metabolomics directly measure substrates and products of biological processes and pathways. Based on instrumentation and throughput advances, the use of metabolomics has only recently become feasible at the population level. This has led to an intense interest in using the new information in combination with genomics, and other omics technologies, to give biological context to the rapidly accumulating associations between genes and diseases or their risk factors. RECENT FINDINGS: The use of metabolomics-genomic associations for the metabolic characterization of genes of interest has confirmed known pathways and permitted the identification of new ones...
January 13, 2017: Current Opinion in Lipidology
https://www.readbyqxmd.com/read/28090731/addition-of-ezetimibe-to-statins-for-patients-at-high-cardiovascular-risk-systematic-review-of-patient-important-outcomes
#2
REVIEW
Yutong Fei, Gordon Henry Guyatt, Paul Elias Alexander, Regina El Dib, Reed A C Siemieniuk, Per Olav Vandvik, Mark E Nunnally, Huda Gomaa, Rebecca L Morgan, Arnav Agarwal, Ying Zhang, Neera Bhatnagar, Frederick A Spencer
Ezetimibe is widely used in combination with statins to reduce low-density lipoprotein. We sought to examine the impact of ezetimibe when added to statins on patient-important outcomes. Medline, EMBASE, CINAHL, and CENTRAL were searched through July, 2016. Randomized controlled trials (RCTs) of ezetimibe combined with statins versus statins alone that followed patients for at least 6 months and reported on at least one of all-cause mortality, cardiovascular deaths, non-fatal myocardial infarctions (MI), and non-fatal strokes were included...
January 16, 2017: Journal of Evaluation in Clinical Practice
https://www.readbyqxmd.com/read/28090367/novel-uses-for-lipid-lowering-agents
#3
REVIEW
Megan Brafford May, Ashley Glode
Statin use leads to a reduction in the downstream products of the mevalonate pathway. Knowledge of this pathway has led scientists to investigate the role of statins in cancer prevention and treatment. Statins appear to possess a variety of pleiotropic effects, including inhibition of cell proliferation; enhanced apoptosis; and modulation of inflammation, endothelial function, and angiogenesis. In cancer specifically, experimental studies have found that statins may induce cancer cell apoptosis and inhibit tumor growth, angiogenesis, and metastasis...
March 2016: Journal of the Advanced Practitioner in Oncology
https://www.readbyqxmd.com/read/28089803/statins-and-diabetes-current-perspectives-and-implications-for-clinicians
#4
EDITORIAL
Charles H Hennekens, Bettina Teng, Marc A Pfeffer
No abstract text is available yet for this article.
January 12, 2017: American Journal of Medicine
https://www.readbyqxmd.com/read/28089735/effects-of-simvastatin-on-cat-1-mediated-arginine-transport-and-no-level-under-high-glucose-conditions-in-conditionally-immortalized-rat-inner-blood-retinal-barrier-cell-lines-tr-ibrb
#5
Temdara Tun, Young-Sook Kang
OBJECTIVE: Hyperglycemia causes the breakdown of the blood-retinal barrier by impairing endothelial nitric oxide synthase (eNOS) function. Statins have many pleiotropic effects such as improving endothelial barrier permeability and increasing eNOS mRNA stability. The objective of this study was to determine effect of simvastatin on l-arginine transport and NO production under high-glucose conditions in conditionally immortalized rat retinal capillary endothelial cell line (TR-iBRB). METHODS: Changes in l-arginine transport uptake and, expression levels of cationic amino acid transporter 1 (CAT-1) and eNOS mRNA were investigated after pre-treatment with simvastatin and NOS inhibitors (l-NMMA and l-NAME) under high-glucose conditions using TR-iBRB, an in vitro model of iBRB...
January 12, 2017: Microvascular Research
https://www.readbyqxmd.com/read/28089685/evaluation-of-drug-drug-interaction-potential-between-sacubitril-valsartan-lcz696-and-statins-using-a-physiologically-based-pharmacokinetic-model
#6
Wen Lin, Tao Ji, Heidi Einolf, Surya Ayalasomayajula, Tsu-Han Lin, Imad Hanna, Tycho Heimbach, Christopher Breen, Venkateswar Jarugula, Handan He
Sacubitril/valsartan (LCZ696) has been approved for the treatment of heart failure. Sacubitril is an in vitro inhibitor of OATPs. In clinical studies, LCZ696 increased atorvastatin Cmax by 1.7-fold and AUC by 1.3-fold, but had little or no effect on simvastatin or simvastatin acid exposure. A PBPK modelling approach was applied to explore the underlying mechanisms behind the statin-specific LCZ696 drug interaction observations. The model incorporated OATP-mediated clearance (CLint,T) for simvastatin and simvastatin acid to successfully describe the PK profiles of either analyte in the absence or presence of LCZ696...
January 12, 2017: Journal of Pharmaceutical Sciences
https://www.readbyqxmd.com/read/28089655/statins-and-primary-prevention-of-venous-thromboembolism-a-systematic-review-and-meta-analysis
#7
Setor K Kunutsor, Samuel Seidu, Kamlesh Khunti
BACKGROUND: Statins have been suggested to have a protective effect on venous thromboembolism (which includes deep vein thrombosis and pulmonary embolism), but the evidence is uncertain. We sought to evaluate the extent to which statins are associated with first venous thromboembolism events. METHODS: We did a systematic review and meta-analysis of observational cohort studies and randomised controlled trials (RCTs). Relevant studies that reported associations between statins and first venous thromboembolism outcomes were identified from MEDLINE, Embase, Web of Science, Cochrane Library, and a manual search of bibliographies for studies published up until July 18, 2016, and from email correspondence with investigators...
January 12, 2017: Lancet Haematology
https://www.readbyqxmd.com/read/28089654/statins-in-prevention-of-venous-thromboembolism
#8
Anetta Undas
No abstract text is available yet for this article.
January 12, 2017: Lancet Haematology
https://www.readbyqxmd.com/read/28089347/virtual-screening-and-experimental-validation-identify-novel-modulators-of-nuclear-receptor-rxr%C3%AE-from-drugbank-database
#9
Dan Xu, Lijun Cai, Shangjie Guo, Lei Xie, Meimei Yin, Ziwen Chen, Hu Zhou, Ying Su, Zhiping Zeng, Xiaokun Zhang
Retinoid X receptor alpha (RXRα), an important ligand-dependent transcription factor, plays a critical role in the development of various cancers and metabolic and neurodegenerative diseases. Therefore, RXRα represents one of the most important targets in modern drug discovery. In this study, Drugbank 2.0 with 1280 old drugs were virtually screened by Glide according to the crystal structure of ligand-binding domain (LBP) of RXRα. 15 compounds selected were tested for their binding and transcriptional activity toward RXRα by Biacore and reporter gene assay, respectively...
December 26, 2016: Bioorganic & Medicinal Chemistry Letters
https://www.readbyqxmd.com/read/28089343/assessment-of-microvascular-endothelial-function-in-type-1-diabetes-using-laser-speckle-contrast-imaging
#10
Alessandra S de M Matheus, Eliete Leão Silva Clemente, Maria de Lourdes Guimarães Rodrigues, Débora Cristina Torres Valença, Marília B Gomes
OBJECTIVE: To test whether laser speckle contrast imaging (LSCI) coupled with physiological post-occlusive reactive hyperemia (PORH) and pharmacological iontophoresis of acetylcholine (ACh) as local vasodilator stimuli could distinguish between cutaneous microvascular responses of Type 1 Diabetes (T1DM)'s patients with endothelial dysfunction and that of healthy controls. METHODS: Patients with T1DM aged ≥12years completed a clinical-epidemiological questionnaire...
January 3, 2017: Journal of Diabetes and its Complications
https://www.readbyqxmd.com/read/28089090/non-alcoholic-fatty-liver-disease-in-patients-with-type-2-diabetes-mellitus-effects-of-statins-and-antidiabetic-drugs
#11
EDITORIAL
Niki Katsiki, Vasilios G Athyros, Dimitri P Mikhailidis
No abstract text is available yet for this article.
December 29, 2016: Journal of Diabetes and its Complications
https://www.readbyqxmd.com/read/28088656/low-dose-aspirin-use-and-survival-in-breast-cancer-patients-a-nationwide-cohort-study
#12
Úna C Mc Menamin, Chris R Cardwell, Carmel M Hughes, Liam J Murray
BACKGROUND: Preclinical evidence from breast cancer cell lines and animal models suggest that aspirin could have anti-cancer properties. In a large breast cancer patient cohort, we investigated whether post-diagnostic low-dose aspirin use was associated with a reduction in the risk of breast cancer-specific mortality. METHODS: We identified 15,140 newly diagnosed breast cancer patients within the Scottish Cancer Registry. Linkages to the Scottish Prescribing Information System provided data on dispensed medications and breast cancer-specific deaths were identified from National Records of Scotland Death Records...
January 12, 2017: Cancer Epidemiology
https://www.readbyqxmd.com/read/28087575/treating-inflammation-and-infection-in-the-21st-century-new-hints-from-decoding-resolution-mediators-and-mechanisms
#13
REVIEW
Charles N Serhan
Practitioners of ancient societies from the time of Hippocrates and earlier recognized and treated the signs of inflammation, heat, redness, swelling, and pain with agents that block or inhibit proinflammatory chemical mediators. More selective drugs are available today, but this therapeutic concept has not changed. Because the acute inflammatory response is host protective to contain foreign invaders, much of today's pharmacopeia can cause serious unwanted side effects, such as immune suppression. Uncontrolled inflammation is now considered pathophysiologic and is associated with many widely occurring diseases such as cardiovascular disease, neurodegenerative diseases, diabetes, obesity, and asthma, as well as classic inflammatory diseases (e...
January 13, 2017: FASEB Journal: Official Publication of the Federation of American Societies for Experimental Biology
https://www.readbyqxmd.com/read/28086966/predictive-value-of-non-fasting-remnant-cholesterol-for-short-term-outcome-of-diabetics-with-new-onset-stable-coronary-artery-disease
#14
Li-Feng Hong, Xiao-Ni Yan, Zhen-Hua Lu, Ying Fan, Fei Ye, Qiong Wu, Song-Hui Luo, Bo Yang, Jian-Jun Li
BACKGROUND: The relationship between non-fasting remnant cholesterol and cardiovascular outcome in the era of potent statin therapy remained to be elucidated. METHODS: A cohort study of three hundred and twenty eight diabetics diagnosed with new-onset stable coronary artery disease (CAD) by coronary angiography were enrolled. All cases were followed up for an average duration of twelve months. The association between baseline remnant cholesterol levels and major cardiovascular outcomes were evaluated using the receivers operating characteristic (ROC) curves and Cox proportional hazards regression analysis...
January 13, 2017: Lipids in Health and Disease
https://www.readbyqxmd.com/read/28081262/efficacy-of-statin-treatment-in-early-stage-chronic-kidney-disease
#15
Eun Yeong Cho, Chana Myoung, Hong-Suk Park, Ae Jin Kim, Han Ro, Jae Hyun Chang, Hyun Hee Lee, Wookyung Chung, Ji Yong Jung
Chronic kidney disease (CKD) represents a major medical challenge and frequently coexists with cardiovascular disease (CVD), which can be treated by statin trerapy. However, whether statin treatment affects renal progression and outcomes in CKD patients remains unclear. We retrospectively reviewed CKD patients at Gachon University Gil Medical Center from 2003-2013. From a total of 14,497 CKD patients, 858 statin users were paired with non-users and analyze with propensity score matching was performed. The outcomes of this study were creatinine doubling, renal death, all-cause mortality, and interactive factors for composite outcomes...
2017: PloS One
https://www.readbyqxmd.com/read/28081164/economic-evaluation-of-pcsk9-inhibitors-in-reducing-cardiovascular-risk-from-health-system-and-private-payer-perspectives
#16
Alejandro Arrieta, Timothy F Page, Emir Veledar, Khurram Nasir
The introduction of Proprotein covertase subtilisin/kexin type 9 (PCSK9) inhibitors has been heralded as a major advancement in reducing low-density lipoprotein cholesterol levels by nearly 50%. However, concerns have been raised on the added value to the health care system in terms of their costs and benefits. We assess the cost-effectiveness of PCSK9 inhibitors based on a decision-analytic model with existing clinical evidence. The model compares a lipid-lowering therapy based on statin plus PCSK9 inhibitor treatment with statin treatment only (standard therapy)...
2017: PloS One
https://www.readbyqxmd.com/read/28079594/impact-of-concurrent-medication-use-on-pancreatic-cancer-survival-seer-medicare-analysis
#17
Muhammad S Beg, Arjun Gupta, David Sher, Sadia Ali, Saad Khan, Ang Gao, Tyler Stewart, Chul Ahn, Jarett Berry, Eric M Mortensen
OBJECTIVES: Preclinical studies have suggested that non-antineoplastic medication use may impact pancreatic cancer biology. We examined the association of several medication classes on pancreatic cancer survival in a large medical claims database. MATERIALS AND METHODS: Histologically confirmed pancreatic adenocarcinoma diagnosed between 2006 and 2009 were analyzed from the Surveillance, Epidemiology, and End Results-Medicare database with available part D data...
January 10, 2017: American Journal of Clinical Oncology
https://www.readbyqxmd.com/read/28079508/management-of-dyslipidemia-in-high-risk-patients-with-recent-onset-rheumatoid-arthritis-targets-still-not-met-despite-specific-recommendations-results-from-the-espoir-cohort-during-the-first-five-years-of-follow-up
#18
Anne Tournadre, Bruno Pereira, Jean-Jacques Dubost, Nathalie Rincheval, Anne Christine Rat, Bernard Combe, Martin Soubrier
OBJECTIVES: Reduction of LDL-cholesterol (LDLc) is essential to decrease the cardiovascular mortality in rheumatoid arthritis (RA). Between 2005 and 2010, French recommendations for dyslipidaemia defined the LDLc target based on the number of cardiovascular risk factors. In 2006, it was recommended to consider LDLc objectives with RA being counted as an additional cardiovascular risk factor. Our objective was to assess lipid target achievement between 2006 and 2010 in a cohort of patients with recent-onset RA...
January 4, 2017: Clinical and Experimental Rheumatology
https://www.readbyqxmd.com/read/28078998/lipoprotein-a-management-pharmacological-and-apheretic-treatment
#19
Ruth Hanssen, Ioanna Gouni-Berthold
Lipoprotein (a) [Lp(a)] is an low-density lipoprotein (LDL)-like particle with an additional apolipoprotein, apolipoprotein (a), [apo(a)] attached to apolipoprotein B. Recent epidemiologic and Mendelian randomization studies have provided evidence that Lp(a) is causally related to the pathogenesis of atherosclerosis and cardiovascular disease (CVD). The risk association between Lp(a) concentrations and CVD is still controversial but seems to be continuous and without an obvious threshold Lp(a) level. Circulating concentrations of Lp(a) are genetically determined; desirable levels are amplt; 50 mg/dl...
January 12, 2017: Current Medicinal Chemistry
https://www.readbyqxmd.com/read/28077495/left-ventricular-wall-motion-abnormalities-are-associated-with-stroke-recurrence
#20
Jeong-Yoon Choi, Jaehyung Cha, Jin-Man Jung, Woo-Keun Seo, Kyungmi Oh, Kyung-Hee Cho, Sungwook Yu
OBJECTIVE: To investigate the role of left ventricular wall motion abnormalities (LVWMA), unrelated to high-risk cardioembolic conditions, in stroke recurrence. METHODS: This study included consecutive acute ischemic stroke patients. Transthoracic echocardiography was performed as a routine evaluation for stroke patients. The outcomes were the time to recurrent any stroke and ischemic stroke. RESULTS: Among 4,316 acute ischemic stroke patients, 430 had LVWMA without high-risk cardioembolic sources...
January 11, 2017: Neurology
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