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https://www.readbyqxmd.com/read/28636269/commentary-on-r-d-trends-away-from-general-medicine-cardiovascular-drugs-can-the-fda-help-reverse-the-trend
#1
R J Meyer
In the latter part of the 20th century, drug development in cardiovascular diseases (CVDs) was a paragon of "modern" therapeutics, bringing about a substantial number of effective, well-tolerated agents targeting some of the most prevalent diseases of the Western world. These drugs were often examples of rational drug development targeting specific pathophysiologic pathways previously elucidated through basic research (e.g., targeting of the renin-angiotensin system or the cholesterol synthesis pathway). The widespread adoption of these ground-breaking medications in practice and into medical guidelines undoubtedly played a role in the fall of morbidity and mortality from CVD in the United States in recent decades...
June 21, 2017: Clinical Pharmacology and Therapeutics
https://www.readbyqxmd.com/read/28636184/pharmacokinetics-pharmacodynamics-of-bococizumab-a-monoclonal-antibody-to-pcsk9-after-single-subcutaneous-injection-at-3-sites-nct-02043301
#2
Ellen Q Wang, Anna Plotka, Joanne Salageanu, Catherine Sattler, Carla Yunis
AIM: To characterize the single-dose pharmacokinetics (PK) and pharmacodynamics (PD) of bococizumab, a monoclonal antibody inhibiting proprotein convertase subtilisin/kexin type 9 (PCSK9), administered subcutaneously (s.c.) to the abdomen, thigh, or upper arm (NCT02043301). METHODS: Seventy-five adults with low-density lipoprotein cholesterol (LDL-C) ≥130 mg/dL and not on background lipid-lowering therapy were randomized (1:1:1) to a single 150-mg s.c. dose of bococizumab administered to the abdomen, thigh, or upper arm...
June 21, 2017: Cardiovascular Therapeutics
https://www.readbyqxmd.com/read/28636182/effects-of-green-tea-on-lipid-metabolism-in-overweight-or-obese-people-a-meta-analysis-of-randomized-controlled-trials
#3
Yuan Fen, Dong Hui, Fang Ke, Gong Jing, Lu Fu Er
SCOPE: The effects of green tea on lipid metabolism were inconsistent. The objective of this meta-analysis was to evaluate the effects of green tea on lipid metabolism in overweight or obese people. METHODS AND RESULTS: We searched randomized controlled trials(RCTs) comparing green tea with a control on lipid metabolism on PUBMED and WEB OF SCIENCE (January 1990 to September 2016), COCHRANE and EMBASE (updated to October 2016), and the Chinese databases CNKI, WanFang and CBMD...
June 21, 2017: Molecular Nutrition & Food Research
https://www.readbyqxmd.com/read/28635586/gc-1-a-thyromimetic-with-multiple-therapeutic-applications-in-liver-disease
#4
Amedeo Columbano, Grazia Chiellini, Marta Anna Kowalik
Thyroid hormones, namely 3,5,3'-triiodo-L-thyronine (T3) and 3,5,3',5'-tetraiodo-L-thyronine (thyroxine or T4), influence a variety of physiological processes that have important implications in fetal development, metabolism, cell growth and proliferation. While THs elicit several beneficial effects on lipid metabolism and improve myocardial contractility, these therapeutically desirable effects are associated to a thyrotoxic state, that severely limits the possible use of THs as therapeutic agents. Therefore, several efforts have been made to develop T3 analogues that could retain the beneficial actions (triglyceride, cholesterol, obesity and body mass lowering), without the adverse TH-dependent side effects...
June 13, 2017: Gene Expression
https://www.readbyqxmd.com/read/28635512/effect-of-simvastatin-on-lipid-accumulation-and-the-expression-of-cxcl16-and-nephrin-in-podocyte-induced-by-oxidized-ldl
#5
Li Wang, Xiujun Yao, Qian Li, Shuzhen Sun
OBJECTIVE: To investigate the effect of simvastatin on lipid accumulation and the expression of CXCL16 and Nephrin in murine podocytes induced by oxidized LDL (OxLDL) in order to explore the mechanism of protection. METHODS: Murine podocytes (MPC5) were incubated with OxLDL (80 μg/ml) at different concentrations of simvastatin (0, 1.0, and 2.0 μg/ml) for 48 hours. Oil red O staining was used for the assessment of lipid accumulation in podocytes, and colorimetric cholesterol detection kit was used for the quantitative measurement...
February 10, 2017: Journal of Investigative Surgery: the Official Journal of the Academy of Surgical Research
https://www.readbyqxmd.com/read/28635327/within-visit-blood-pressure-variability-and-cardiovascular-risk-factors-in-hypertensive-patients-with-non-dialysis-chronic-kidney-disease
#6
Kengo Azushima, Hiromichi Wakui, Kazushi Uneda, Sona Haku, Ryu Kobayashi, Kohji Ohki, Sho Kinguchi, Kotaro Haruhara, Tetsuya Fujikawa, Yoshiyuki Toya, Satoshi Umemura, Kouichi Tamura
As there may be an association between within-visit blood pressure (BP) variability and cardiovascular disease (CVD), we investigated the clinical significance of this BP variability in non-dialysis chronic kidney disease (CKD) patients. MATERIALS AND METHODS: According to the median of coefficient of variation (CV) of three systolic BP (SBP) readings within a single visit, we divided hypertensive patients with stage G1-4 CKD already treated with antihypertensive therapy into the high SBP-CV group and the low SBP-CV group...
June 21, 2017: Clinical and Experimental Hypertension: CHE
https://www.readbyqxmd.com/read/28634674/prognostic-impact-of-nutritional-status-assessed-by-the-controlling-nutritional-status-score-in-patients-with-stable-coronary-artery-disease-undergoing-percutaneous-coronary-intervention
#7
Hideki Wada, Tomotaka Dohi, Katsumi Miyauchi, Shinichiro Doi, Hirokazu Konishi, Ryo Naito, Shuta Tsuboi, Manabu Ogita, Takatoshi Kasai, Shinya Okazaki, Kikuo Isoda, Satoru Suwa, Hiroyuki Daida
BACKGROUND: Recently, malnutrition has been shown to be related to worse clinical outcomes in patients with heart failure. However, the association between nutritional status and clinical outcomes in patients with coronary artery disease (CAD) remains unclear. We investigated the prognostic value of malnutrition assessed by the Controlling Nutritional Status (CONUT; range 0-12, higher = worse, consisting of serum albumin, cholesterol and lymphocytes) score in patients with CAD. METHODS: The CONUT score was measured on admission in a total of 1987 patients with stable CAD who underwent elective percutaneous coronary intervention (PCI) between 2000 and 2011...
June 20, 2017: Clinical Research in Cardiology: Official Journal of the German Cardiac Society
https://www.readbyqxmd.com/read/28634625/serum-antioxidant-capacity-biochemical-profile-and-body-composition-of-breast-cancer-survivors-in-a-randomized-mediterranean-dietary-intervention-study
#8
Maria Skouroliakou, D Grosomanidis, P Massara, C Kostara, P Papandreou, D Ntountaniotis, G Xepapadakis
PURPOSE: Increasing evidence suggests that Mediterranean Diet (MD) is correlated with reduced risk of breast cancer (BC) and cancer mortality, since it modifies patients' serum antioxidant capacity, body composition and biochemical parameters. The aim of the study was to investigate whether a dietary intervention based on MD has a beneficial effect on these factors. METHODS: In this intervention study, seventy female BC survivors were randomly assigned to (1) the intervention group (personalized dietary intervention based on MD) and (2) the control group (received the updated American Cancer Society Guidelines on Nutrition and Physical Activity for Cancer Prevention and ad libitum diet)...
June 20, 2017: European Journal of Nutrition
https://www.readbyqxmd.com/read/28634575/association-between-plasmatic-ceramides-profile-and-ast-alt-ratio-c14-0-ceramide-as-predictor-of-hepatic-steatosis-in-adolescents-independently-of-obesity
#9
Jorge Maldonado-Hernández, Gabriela E Saldaña-Dávila, Mónica I Piña-Aguero, Benjamín A Núñez-García, Mardia G López-Alarcón
OBJECTIVE: To assess the association between plasma ceramides and hepatic steatosis (HS) in adolescents, independently of obesity. MATERIALS AND METHODS: Ninety-four adolescents from two previous studies conducted and published by our crew were included. Study subjects were stratified in three groups: normal weight (n = 18), obesity (n = 34), and obesity + HS (n = 42). The presence of HS was defined when ALT/AST ratio was <1. Ceramides subspecies (C14:0, C16:0, C18:0, C24:0, and C24:1) were determined by LC/MS...
2017: Canadian Journal of Gastroenterology & Hepatology
https://www.readbyqxmd.com/read/28634572/a-helicobacter-pylori-homolog-of-eukaryotic-flotillin-is-involved-in-cholesterol-accumulation-epithelial-cell-responses-and-host-colonization
#10
Melanie L Hutton, Kimberley D'Costa, Amanda E Rossiter, Lin Wang, Lorinda Turner, David L Steer, Seth L Masters, Ben A Croker, Maria Kaparakis-Liaskos, Richard L Ferrero
The human pathogen Helicobacter pylori acquires cholesterol from membrane raft domains in eukaryotic cells, commonly known as "lipid rafts." Incorporation of this cholesterol into the H. pylori cell membrane allows the bacterium to avoid clearance by the host immune system and to resist the effects of antibiotics and antimicrobial peptides. The presence of cholesterol in H. pylori bacteria suggested that this pathogen may have cholesterol-enriched domains within its membrane. Consistent with this suggestion, we identified a hypothetical H...
2017: Frontiers in Cellular and Infection Microbiology
https://www.readbyqxmd.com/read/28634364/lipid-changes-8-years-post-gastric-bypass-in-adolescents-with-severe-obesity-fabs-5-study
#11
Amy S Shah, Todd Jenkins, Zhiqian Gao, Stephen R Daniels, Elaine M Urbina, Shelley Kirk, Robert Siegel, Thomas H Inge
OBJECTIVE: Severe obesity in adolescents is increasing and few effective treatments exist. Bariatric surgery is one option, but the extent to which surgery influences cardiovascular risk factors over time in youth is not clear. We hypothesized that Roux-en Y gastric bypass (RYGB) would be associated with sustained improvements in lipids over time (>5 years). PARTICIPANTS/METHODS: Youth who underwent RYGB from 2001-2007 were recruited for the Follow-up of Adolescent Bariatric Surgery-5+ (FABS-5+) in 2011-2014...
June 21, 2017: International Journal of Obesity: Journal of the International Association for the Study of Obesity
https://www.readbyqxmd.com/read/28634218/high-quality-statin-trials-support-the-2013-acc-aha-cholesterol-guidelines-after-hope-3-the-multi-ethnic-study-of-atherosclerosis
#12
Martin B Mortensen, Matthew J Budoff, Dong Li, Khurram Nasir, Michael J Blaha, Veit Sandfort, Carlos J Rodriguez, Pamela Ouyang, Erling Falk
The 2013 American College of Cardiology/American Heart Association (ACC/AHA) guideline on cholesterol treatment to prevent atherosclerotic cardiovascular disease (ASCVD) has been criticized for lowering the risk thresholds for primary prevention with statin therapy. Although the ≥ 7.5% (class I) and ≥ 5% (class IIa) 10-year ASCVD risk thresholds were identified as new indications for treatment by extrapolating results obtained in randomized controlled trials (RCT) of statin therapy, results from population-based European cohorts indicate that >30% of individuals eligible for statin therapy by class I recommendations do not have RCT data supporting statin efficacy...
June 20, 2017: Circulation
https://www.readbyqxmd.com/read/28634191/cd36-knockout-mice-are-protected-against-lithogenic-diet-induced-gallstones
#13
Yan Xie, Vincenza Cifarelli, Terri Pietka, Elizabeth P Newberry, Susan M Kennedy, Amin Khalifeh-Soltani, Robin Clugston, Kamran Atabai, Nada A Abumrad, Nicholas O Davidson
The scavenger receptor and multiligand transporter CD36 functions to promote cellular free fatty acid uptake and regulates aspects of both hepatic and intestinal cholesterol metabolism. However, the role of CD36 in regulating canalicular and biliary cholesterol transport and secretion is unknown. Here we show that germline Cd36 knockout mice are protected against lithogenic diet (LD) induced gallstones compared to congenic (C57BL6/J) controls. Cd36 knockout mice crossed into congenic L-Fabp knockout mice (DKO mice) demonstrated protection against LD induced gallstones, reversing the susceptibility phenotype observed in L-Fabp knockout mice...
June 20, 2017: Journal of Lipid Research
https://www.readbyqxmd.com/read/28634189/reduced-platelet-count-but-no-major-platelet-function-abnormalities-are-associated-with-loss-of-function-atp-binding-cassette-1-abca1-gene-mutations
#14
Pietro Minuz, Alessandra Meneguzzi, Eti Alessandra Femia, Cristiano Fava, Stefano Calabria, Mariangela Scavone, Donatella Benati, Giovanni Poli, Carlo Zancanaro, Sebastiano Calandra, Tiziano Lucchi, Marco Cattaneo
Loss of function mutations of the the ATP-binding cassette-1 (ABCA1) gene are the cause of Tangier disease (TD) in homozygous subjects and familial HDL deficiency (FHD) in heterozygous subjects. These disorders are characterized by reduced plasma HDL-cholesterol and altered efflux of cholesterol from cells. Previous studies in TD patients and ABCA1(-/-) murine models reported defects in platelet count, morphology and function, but the issue is still controversial. We analysed three subjects with low to very low HDL cholesterol levels due to loss of function mutations of the ABCA1 gene...
June 20, 2017: Clinical Science (1979-)
https://www.readbyqxmd.com/read/28633872/frozen-yogurt-and-ice-cream-were-less-healthy-than-yogurt-and-adding-toppings-reduced-their-nutrition-value-evidence-from-1999-2014-national-health-and-nutrition-examination-survey
#15
Ruopeng An, Ning Jiang
It was hypothesized that frozen yogurt and ice cream would be less healthy than yogurt. We examined daily energy and nutrient intake from yogurt, frozen yogurt, and ice cream among US adults. In-person 24-hour dietary recall data (n=6453) came from the 1999-2014 National Health and Nutrition Examination Survey. Regression analyses were performed to examine the differences in energy/nutrient intake from frozen yogurt and ice cream (with/without toppings) in comparison to yogurt. Approximately 5.3%, 0.9%, and 14...
June 2017: Nutrition Research
https://www.readbyqxmd.com/read/28633869/baccaurea-angulata-fruit-juice-ameliorates-altered-hematological-and-biochemical-biomarkers-in-diet-induced-hypercholesterolemic-rabbits
#16
Idris Adewale Ahmed, Maryam Abimbola Mikail, Muhammad Ibrahim
Hypercholesterolemia is an important risk factor linked to the alteration of blood hematology and clinical chemistry associated with the development and progression of atherosclerosis. Previous studies have demonstrated the safety and potential health benefits of Baccaurea angulata (BA) fruit. We hypothesized that the oral administration of BA fruit juice could ameliorate the alteration in the hematological and biochemical biomarkers of diet-induced hypercholesterolemic rabbits. The aim of this study was to investigate the effects of different doses of BA juice on the hematological and biochemical biomarkers in normo- and hypercholesterolemic rabbits...
June 2017: Nutrition Research
https://www.readbyqxmd.com/read/28633641/expression-levels-of-atherosclerosis-associated-mir-143-and-mir-145-in-the-plasma-of-patients-with-hyperhomocysteinaemia
#17
Kejian Liu, Saiyare Xuekelati, Yue Zhang, Yin Yin, Yue Li, Rui Chai, Xinwei Li, Yi Peng, Jiangdong Wu, Xiaomei Guo
BACKGROUND: An elevated level of homocysteine (Hcy) in the blood is designated hyperhomocysteinaemia (Hhcy) and is regarded as a strong risk factor for the development of atherosclerosis (ATH), although the association remains controversial. Considered to be essential gene expression regulators, micro-RNAs (miRNAs) modulate cardiovascular disease development and thus can be regarded as potential biomarkers and therapeutic targets in atherosclerosis. The aim of the current study is to investigate the expression levels of atherosclerosis-associated miR-143 and miR-145 in Hhcy patients and predict the progress of atherosclerosis in Hhcy patients...
June 20, 2017: BMC Cardiovascular Disorders
https://www.readbyqxmd.com/read/28633585/lipoprotein-a-activated-immunity-insulin-resistance-and-new-onset-diabetes
#18
Ayşem Kaya, Altan Onat, Hüsniye Yüksel, Günay Can, Murat Yüksel, Evin Ademoğlu
OBJECTIVES: Some evidence suggests that serum lipoprotein[Lp](a) may be inversely linked to type-2 diabetes. We aimed to determine in nondiabetic people the relationship of serum [Lp](a) with insulin resistance and new-onset diabetes (NOD). MATERIALS AND METHODS: Population-based middle-aged adults (n=1685) were categorized by fasting glucose and stratified to gender, having excluded prevalent diabetic subjects. NOD (n=90) occurred over a median 5 years' follow-up...
June 21, 2017: Postgraduate Medicine
https://www.readbyqxmd.com/read/28633452/threshold-effects-of-circulating-angiopoietin-like-3-levels-on-plasma-lipoproteins
#19
Sergio Fazio, Jessica Minnier, Michael D Shapiro, Sotirios Tsimikas, Patrizia Tarugi, Maurizio R Averna, Marcello Arca, Hagai Tavori
Context: Angiopoietin-like 3 (ANGPTL3) deficiency in plasma due to loss-of-function (LOF) gene mutations causes familial combined hypobetalipoproteinemia (FHBL) type 2 in homozygotes. However, the lipid phenotype in heterozygotes is much milder and does not appear to relate directly to ANGPTL3 levels. Furthermore, the low LDL phenotype in carriers of ANGPTL3 mutations is unexplained. Objective: To determine whether a reduction below a critical threshold in plasma ANGPTL3 levels is a determinant of lipoprotein metabolism in FHBL2, and to study the whether PCSK9 is involved in determining low LDL levels in this condition...
June 19, 2017: Journal of Clinical Endocrinology and Metabolism
https://www.readbyqxmd.com/read/28633288/quantifying-the-added-value-of-repeated-measures
#20
Andrew E Moran, Kiang Liu
Meaningful inference in epidemiology relies on accurate exposure measurement. In longitudinal observational studies, more exposure data in the form of repeated measures in the same individuals adds useful information. But exactly how much do repeated measures add, incremental to the information provided by baseline measures? In this issue of the American Journal of Epidemiology, Paige et al. quantified the value of adding repeated cholesterol and blood pressure measurements to baseline measurements in a meta-analysis of individual participant data of 38 longitudinal cohort studies...
June 12, 2017: American Journal of Epidemiology
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