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https://www.readbyqxmd.com/read/29152786/neurocognitive-performance-after-pcsk9-inhibitor-therapy-current-state-of-the-evidence
#1
Cosimo Andrea Stamerra, Paolo Di Giosia, Paolo Giorgini, Martina De Feo, Davide Grassi, Claudio Ferri, Amirhossein Sahebkar
No abstract text is available yet for this article.
November 20, 2017: Journal of Neuroscience Research
https://www.readbyqxmd.com/read/29148854/comparative-effectiveness-of-lipid-lowering-treatments-to-reduce-cardiovascular-disease
#2
Dong-Churl Suh, Scott K Griggs, Emmett R Henderson, Seung-Mi Lee, Taehwan Park
With the advent of a new drug class - the proprotein convertase subtilisin/kexin type 9 (PCSK9) inhibitors, patients have another treatment option for lowering their high levels of low-density lipoprotein cholesterol (LDL-C) in recent years. The objective of this study was to systematically review the cost-effectiveness of lipid-lowering agents such as statins, ezetimibe, and PCSK9 inhibitors. Areas covered: Based on PubMed, Embase, and Cochrane Database of Systematic Reviews, we identified a total of 29 relevant articles...
November 17, 2017: Expert Review of Pharmacoeconomics & Outcomes Research
https://www.readbyqxmd.com/read/29148099/circulating-pcsk9-is-lowered-acutely-following-surgery
#3
Irena Druce, Hussein Abujrad, Seham Chaker, Hilary Meggison, Andrew Hill, Angela Raymond, Janice Mayne, Teik Chye Ooi
BACKGROUND: A decrease in serum low-density lipoprotein cholesterol (LDL-C) is well documented after acute stress. Plasma proprotein convertase subtilisin kexin 9 (PCSK9), which promotes degradation of low-density lipoprotein receptor (LDL-R) resulting in reduced plasma clearance of low-density lipoproteins (LDL) and an increase in serum LDL-C, would be predicted to decrease. Yet, a few studies have demonstrated an increase 1-8 days after acute stress. Our objective was to assess the earlier status of plasma PCSK9, within the first 24 hours of onset of stress...
November 17, 2017: Journal of Clinical Laboratory Analysis
https://www.readbyqxmd.com/read/29146683/pcsk9-variants-ldl-cholesterol-and-neurocognitive-impairment-the-reasons-for-geographic-and-racial-differences-in-stroke-regards-study
#4
Matthew T Mefford, Robert S Rosenson, Mary Cushman, Michael E Farkouh, Leslie A McClure, Virginia G Wadley, Marguerite R Irvin, Vera A Bittner, Monika M Safford, Ransi Somaratne, Keri L Monda, Paul Muntner, Emily B Levitan
Background -Despite concerns about adverse neurocognitive events raised by prior trials, pharmacologic PCSK9 inhibition was not associated with neurocognitive effects in a recent phase 3 randomized trial. PCSK9 loss-of-function (LOF) variants that result in life-long exposure to low LDL-C can provide information on the potential long-term effects of low LDL-C on neurocognitive impairment and decline. Methods -We investigated the association between PCSK9 LOF variants and neurocognitive impairment and decline among African-American REasons for Geographic and Racial Differences in Stroke (REGARDS) study participants with (n=241) and without (n=10,454) C697X or Y142X LOF variants...
November 16, 2017: Circulation
https://www.readbyqxmd.com/read/29142395/biological-effect-of-cynara-cardunculus-on-kidney-status-of-hypercholesterolemic-rats
#5
Abdullah Glil Alkushi
Context: Cynara cardunculus or artichoke thistle belongs to the sunflower family and has a variety of cultivable forms. Historically, it was cultivated as a vegetable, but more recently, it is being used in cheese and biofuel preparation. Artichoke leaf extracts are also known for its medicinal purposes, particularly in reducing the elevated cholesterol levels in blood. Hypercholesterolemia (HC) is also associated with other complications such as impaired renal function and diabetes mellitus...
October 2017: Pharmacognosy Magazine
https://www.readbyqxmd.com/read/29133605/low-density-lipoprotein-cholesterol-lowering-with-evolocumab-and-outcomes-in-patients-with-peripheral-artery-disease-insights-from-the-fourier-trial-further-cardiovascular-outcomes-research-with-pcsk9-inhibition-in-subjects-with-elevated-risk
#6
Marc P Bonaca, Patrice Nault, Robert P Giugliano, Anthony C Keech, Armando Lira Pineda, Estella Kanevsky, Julia Kuder, Sabina A Murphy, J Wouter Jukema, Basil S Lewis, Lale Tokgozoglu, Ransi Somaratne, Peter S Sever, Terje R Pedersen, Marc S Sabatine
BACKGROUND : The PCSK9 (proprotein convertase subtilisin/kexin type 9) inhibitor evolocumab reduced low-density lipoprotein cholesterol and cardiovascular events in the FOURIER trial (Further Cardiovascular Outcomes Research With PCSK9 Inhibition in Subjects With Elevated Risk). We investigated the efficacy and safety of evolocumab in patients with peripheral artery disease (PAD) as well as the effect on major adverse limb events. METHODS : FOURIER was a randomized trial of evolocumab versus placebo in 27 564 patients with atherosclerotic disease on statin therapy followed for a median of 2...
November 13, 2017: Circulation
https://www.readbyqxmd.com/read/29131148/structure-guided-chemical-modification-of-guide-rna-enables-potent-non-viral-in-vivo-genome-editing
#7
Hao Yin, Chun-Qing Song, Sneha Suresh, Qiongqiong Wu, Stephen Walsh, Luke Hyunsik Rhym, Esther Mintzer, Mehmet Fatih Bolukbasi, Lihua Julie Zhu, Kevin Kauffman, Haiwei Mou, Alicia Oberholzer, Junmei Ding, Suet-Yan Kwan, Roman L Bogorad, Timofei Zatsepin, Victor Koteliansky, Scot A Wolfe, Wen Xue, Robert Langer, Daniel G Anderson
Efficient genome editing with Cas9-sgRNA in vivo has required the use of viral delivery systems, which have limitations for clinical applications. Translational efforts to develop other RNA therapeutics have shown that judicious chemical modification of RNAs can improve therapeutic efficacy by reducing susceptibility to nuclease degradation. Guided by the structure of the Cas9-sgRNA complex, we identify regions of sgRNA that can be modified while maintaining or enhancing genome-editing activity, and we develop an optimal set of chemical modifications for in vivo applications...
November 13, 2017: Nature Biotechnology
https://www.readbyqxmd.com/read/29130084/welsh-onion-extract-inhibits-pcsk9-expression-contributing-to-the-maintenance-of-the-ldlr-level-under-lipid-depletion-conditions-of-hepg2-cells
#8
Hyo-Kyoung Choi, Jin-Taek Hwang, Tae-Gyu Nam, Sung Hee Kim, Dong-Kook Min, Sahng Wook Park, Min-Yu Chung
Statins mediate the transactivation of PCSK9, which in turn limits their cholesterol-lowering effects via LDL receptor (LDLR) degradation. The objective of the present study was to investigate the mechanism of action by which Welsh onion (Allium fistulosum L. [family Amaryllidaceae]) extract (WOE) regulates LDLR and PCSK9. HepG2 cells were cultured under lipid depletion conditions using a medium supplemented with delipidated serum (DLPS). WOE (50, 100, 200, and 400 μg ml(-1)) significantly attenuated the DLPS-mediated increases in LDLR, PCSK9, and SREBP2 gene expression...
November 13, 2017: Food & Function
https://www.readbyqxmd.com/read/29129821/association-between-lipoprotein-a-and-proprotein-convertase-substilisin-kexin-type-9-in-patients-with-heterozygous-familial-hypercholesterolemia-a-case-control-study
#9
Di Sun, Sha Li, Xi Zhao, Na-Qiong Wu, Cheng-Gang Zhu, Yuan-Lin Guo, Ying Gao, Ping Qing, Chuan-Jue Cui, Geng Liu, Jing Sun, Qian Dong, Jian-Jun Li
BACKGROUND: Recent data have suggested an important role of lipoprotein (a) [Lp(a)] and proprotein convertase substilisin/kexin type 9 (PCSK9) in the development of atherosclerotic cardiovascular disease (ASCVD) in both general population and family hypercholesterolemia (FH), while the relation of Lp(a) to PCSK9 has not been examined. OBJECTIVE: The aim of the present study was to investigate the association between plasma PCSK9 and Lp(a)in patients with heterozygous FH (HeFH)...
November 9, 2017: Metabolism: Clinical and Experimental
https://www.readbyqxmd.com/read/29127338/identification-and-in-vitro-characterization-of-two-new-pcsk9-gain-of-function-variants-found-in-patients-with-familial-hypercholesterolemia
#10
Maria Donata Di Taranto, Asier Benito-Vicente, Carola Giacobbe, Kepa Belloso Uribe, Paolo Rubba, Aitor Etxebarria, Ornella Guardamagna, Marco Gentile, Cesar Martín, Giuliana Fortunato
Familial hypercholesterolemia (FH) is an autosomal dominant disease caused by pathogenic variants in genes encoding for LDL receptor (LDLR), Apolipoprotein B and Proprotein convertase subtilisin/kexin type 9 (PCSK9). Among PCSK9 variants, only Gain-of- Function (GOF) variants lead to FH. Greater attention should be paid to the classification of variants as pathogenic. Two hundred sixty nine patients with a clinical suspect of FH were screened for variants in LDLR and the patients without pathogenic variants were screened for variants in PCSK9 and APOB...
November 10, 2017: Scientific Reports
https://www.readbyqxmd.com/read/29122809/eligibility-for-pcsk9-inhibitors-according-to-american-college-of-cardiology-acc-and-european-society-of-cardiology-european-atherosclerosis-society-esc-eas-guidelines-after-acute-coronary-syndromes
#11
Baris Gencer, Konstantinos C Koskinas, Lorenz Räber, Alexios Karagiannis, David Nanchen, Reto Auer, David Carballo, Sebastian Carballo, Roland Klingenberg, Dik Heg, Christian M Matter, Thomas F Lüscher, Nicolas Rodondi, François Mach, Stephan Windecker
BACKGROUND: The American College of Cardiology (ACC) and European Society of Cardiology/European Atherosclerosis Society (ESC/EAS) have recently published recommendations for the use of proprotein convertase subtilisin/kexin-9 (PCSK9) inhibitors in situations of very high risk. We aim to assess in the real world the suitability of PCSK9 inhibitors for acute coronary syndromes. METHODS AND RESULTS: We analyzed a prospective Swiss cohort of 2023 patients hospitalized for acute coronary syndromes between 2009 and 2014 with available data for low-density lipoprotein cholesterol and lipid-lowering therapy at 1 year...
November 9, 2017: Journal of the American Heart Association
https://www.readbyqxmd.com/read/29121222/neurological-effects-of-proprotein-convertase-subtilisin-kexin-type-9-inhibitors-direct-comparisons
#12
Navkaranbir S Bajaj, Nirav Patel, Rajat Kalra, Amier Ahmad, Anand Venkatraman, Garima Arora, Pankaj Arora
Aims: Proprotein convertase subtilisin/kexin type 9 (PCSK9) inhibitors considerably alter the lipid profile. We sought to examine rates of ischemic stroke, and neurocognitive deficits in patients treated with and without PCSK9 inhibitors. Methods and Results: Randomized controlled trials (RCTs) reporting rates of ischemic stroke, and neurocognitive deficits in patients using PCSK9 inhibitors were identified. Standard meta-analysis techniques were used to compare these outcomes among patients treated with and without PCSK9 inhibitors, and the two U...
October 6, 2017: European Heart Journal. Quality of Care & Clinical Outcomes
https://www.readbyqxmd.com/read/29120899/association-of-a-3-untranslated-region-polymorphism-in-proprotein-convertase-subtilisin-kexin-type-9-with-hiv-viral-load-and-cd4-levels-in-hiv-hepatitis-c-virus-coinfected-women
#13
Mark H Kuniholm, Hua Liang, Kathryn Anastos, Deborah Gustafson, Seble Kassaye, Marek Nowicki, Beverly E Sha, Emilia J Pawlowski, Stephen J Gange, Bradley E Aouizerat, Tatiana Pushkarsky, Michael I Bukrinsky, Vinayaka R Prasad
OBJECTIVE: To assess variation in genes that regulate cholesterol metabolism in relation to the natural history of HIV infection. DESIGN: Cross-sectional and longitudinal analysis of the Women's Interagency HIV Study. METHODS: We examined 2050 single nucleotide polymorphisms (SNPs) in 19 genes known to regulate cholesterol metabolism in relation to HIV viral load and CD4 T-cell levels in a multiracial cohort of 1066 antiretroviral therapy-naive women...
November 28, 2017: AIDS
https://www.readbyqxmd.com/read/29120697/enhancing-antibody-patent-protection-using-epitope-mapping-information
#14
Xiaoxiang Deng, Ulrich Storz, Benjamin J Doranz
As the $100B therapeutic monoclonal antibody (mAb) market continues to grow, developers of therapeutic mAbs increasingly face the need to strengthen patent protection of their products and enforce their patents in courts. In view of changes in the patent law landscape, patent applications are strategically using information on the precise binding sites of their mAbs, i.e., the epitopes, to support patent novelty, non-obviousness, subject matter, and a tightened written description requirement for broad genus antibody claims...
November 9, 2017: MAbs
https://www.readbyqxmd.com/read/29118349/diabetes-anti-pcsk9-antibodies-beneficial-or-inducers-of-diabetes
#15
Rutger Verbeek, G Kees Hovingh
No abstract text is available yet for this article.
November 9, 2017: Nature Reviews. Endocrinology
https://www.readbyqxmd.com/read/29117276/clinical-efficacy-and-safety-of-evolocumab-in-high-risk-patients-receiving-a-statin-secondary-analysis-of-patients-with-low-ldl-cholesterol-levels-and-in-those-already-receiving-a-maximal-potency-statin-in-a-randomized-clinical-trial
#16
Robert P Giugliano, Anthony Keech, Sabina A Murphy, Kurt Huber, S Lale Tokgozoglu, Basil S Lewis, Jorge Ferreira, Armando Lira Pineda, Ransi Somaratne, Peter S Sever, Terje R Pedersen, Marc S Sabatine
Importance: Current guidelines for atherosclerotic cardiovascular disease focus on high-intensity statins and targeting or using a threshold low-density lipoprotein cholesterol (LDL-C) level of less than 70 mg/dL for the highest-risk patients. Whether further reduction of LDL-C beyond these boundaries would be beneficial is unknown. Objective: To compare outcomes of evolocumab vs placebo in patients with stable atherosclerotic cardiovascular disease and a baseline LDL-C of less than 70 mg/dL and in those receiving background treatment with a maximal-potency statin...
November 8, 2017: JAMA Cardiology
https://www.readbyqxmd.com/read/29116337/effects-of-monoclonal-antibodies-against-pcsk9-on-clinical-cardiovascular-events-a%C3%A2-meta-analysis-of-randomized-controlled-trials
#17
Y Zhu, X Shen, Q Jiang, Z Wang, Z Wang, X Dong, J Li, Q Han, J Zhao, B Wang, L Liu
BACKGROUND: The present meta-analysis was designed to improve statistical power and review the effects of monoclonal antibodies against PCSK9 on clinical cardiovascular events. METHODS: PubMed, Embase, Web of Science, and the Cochrane Library were searched from inception to May 2017. Studies considered to be eligible were randomized controlled trials about the effects of monoclonal antibodies against PCSK9 on clinical cardiovascular events. The primary endpoint was positively adjudicated cardiovascular events; the secondary endpoint comprised cardiac mortality, myocardial infarction (MI), coronary revascularization, stroke, and hospitalization for unstable angina...
November 7, 2017: Herz
https://www.readbyqxmd.com/read/29113347/lunasin-functionally-enhances-ldl-uptake-via-inhibiting-pcsk9-and-enhancing-ldlr-expression-in-vitro-and-in-vivo
#18
Lili Gu, Yue Wang, Yaqiong Xu, Qinghua Tian, Gaoxin Lei, Cheng Zhao, Zhan Gao, Qin Pan, Wenfeng Zhao, Liu Nong, Shuhua Tan
Proprotein convertase subtilisin/kexin type 9 (PCSK9) is a serine protease which regulates serum low-density lipoprotein cholesterol (LDL-C) levels by promoting the degradation of the hepatic low-density lipoprotein receptor (LDLR), and has become an attractive therapeutic target for cholesterol lowering intervention. Lunasin, a 43-amino acid polypeptide initially isolated from soybean, has been previously proven to possess cholesterol lowering activity. Here we identified the down-regulation of PCSK9 expression by lunasin as one new mechanism that increased cell-surface LDLR level and enhanced LDL uptake in vitro and in vivo...
October 6, 2017: Oncotarget
https://www.readbyqxmd.com/read/29109005/evaluation-of-pcsk9-levels-and-its-genetic-polymorphisms-in-women-with-polycystic-ovary-syndrome
#19
Luana B Xavier, Mirelle O Sóter, Mariana F Sales, Daisy K Oliveira, Helton J Reis, Ana L Candido, Fernando M Reis, Ieda O Silva, Karina B Gomes, Cláudia N Ferreira
Dyslipidemia is one of the common metabolic disorders in Polycystic Ovary Syndrome (PCOS). Proprotein convertase subtilisin kexin type 9 (PCSK9) is a new component of lipid metabolism and correlated to the development of dyslipidemia and atherosclerosis. This protein acts by preventing the recycling of LDL receptors (LDL-r) back to the cell surface and thus generates higher levels of LDLc. The objective of this study was to evaluate the PCSK9 polymorphisms rs505151 (c.2009A>G), rs562556 (c.1420A>G) and rs11206510 (T>C) and plasma PCSK9 levels in PCOS...
November 3, 2017: Gene
https://www.readbyqxmd.com/read/29105679/-a-practical-tool-for-easier-compilation-of-aifa-italian-medicines-agency-web-based-registry-for-pcsk9-inhibitor-prescription
#20
Claudio Bilato, Maurizio Anselmi, Roberto Cemin, Nadia Citroni, Loris Roncon, Alberto Zambon, Sabina Zambon, Maria Grazia Zenti
No abstract text is available yet for this article.
November 2017: Giornale Italiano di Cardiologia
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