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https://www.readbyqxmd.com/read/29353350/clinical-pharmacokinetics-and-pharmacodynamics-of-evolocumab-a-pcsk9-inhibitor
#1
REVIEW
Sreeneeranj Kasichayanula, Anita Grover, Maurice G Emery, Megan A Gibbs, Ransi Somaratne, Scott M Wasserman, John P Gibbs
Proprotein convertase subtilisin/kexin type 9 (PCSK9) increases plasma low-density lipoprotein cholesterol (LDL-C) by decreasing expression of the LDL receptor on hepatic cells. Evolocumab is a human monoclonal immunoglobulin G2 that binds specifically to human PCSK9 to reduce LDL-C. Evolocumab exhibits nonlinear kinetics as a result of binding to PCSK9. Elimination is predominantly through saturable binding to PCSK9 at lower concentrations and a nonsaturable proteolytic pathway at higher concentrations. The effective half-life of evolocumab is 11-17 days...
January 20, 2018: Clinical Pharmacokinetics
https://www.readbyqxmd.com/read/29353277/a-critical-review-of-the-consensus-statement-from-the-european-atherosclerosis-society-consensus-panel-2017
#2
Harumi Okuyama, Tomohito Hamazaki, Rokuro Hama, Yoichi Ogushi, Tetsuyuki Kobayashi, Naoki Ohara, Hajime Uchino
BACKGROUND: The Consensus Statement from the European Atherosclerosis Society (EAS) Consensus Panel 2017 concludes on the basis of 3 different types of clinical studies that low-density lipoprotein (LDL) causes atherosclerotic cardiovascular disease (ASCVD). In Mendelian randomization studies, rare genetic mutations affecting LDL receptor function were found to cause higher or lower LDL-C levels, which are associated with correspondingly altered ASCVD risk. In prospective cohort studies and randomized controlled trials (RCTs) of statins, a remarkably consistent log-linear association was demonstrated between the absolute magnitude of LDL-C exposure and ASCVD risk...
January 19, 2018: Pharmacology
https://www.readbyqxmd.com/read/29353225/spectrum-of-mutations-in-index-patients-with-familial-hypercholesterolemia-in-singapore-single-center-study
#3
Sharon Li Ting Pek, Sanjaya Dissanayake, Jessie Choi Wan Fong, Michelle Xueqin Lin, Eric Zit Liang Chan, Justin I-Shing Tang, Chee Wan Lee, Hean Yee Ong, Chee Fang Sum, Su Chi Lim, Subramaniam Tavintharan
BACKGROUND AND AIMS: Familial hypercholesterolemia (FH) is an autosomal dominant genetic disease characterized by the presence of high plasma low density lipoproteins cholesterol (LDL-c). Patients with FH, with mutation detected, are at increased risk of premature cardiovascular disease compared to those without mutations. The aim of the study was to assess the type of mutations in patients, clinically diagnosed with FH in Singapore. METHODS: Patients (probands) with untreated/highest on-treatment LDL-c>4...
December 27, 2017: Atherosclerosis
https://www.readbyqxmd.com/read/29353098/the-anti-inflammatory-effects-of-statins-on-patients-with-rheumatoid-arthritis-a-systemic-review-and-meta-analysis-of-15-randomized-controlled-trials
#4
REVIEW
Guo-Min Li, Jie Zhao, Bing Li, Xiao-Fei Zhang, Jian-Xiong Ma, Xin-Long Ma, Jun Liu
BACKGROUND: Over the past several years, numerous studies investigated the anti-inflammatory effects of statin on patients with RA. However, the findings of the individual studies were often inconsistent or conflicting. MATERIALS AND METHODS: The Pubmed, Web of Science, Embase, Cochrane Library and CNKI literature databases were searched in order to identify randomized controlled clinical trials where the association between the anti-inflammatory effect of statin and RA was investigated...
January 15, 2018: Autoimmunity Reviews
https://www.readbyqxmd.com/read/29353041/fads2-inhibition-in-essential-fatty-acid-deficiency-induces-hepatic-lipid-accumulation-via-impairment-of-very-low-density-lipoprotein-vldl-secretion
#5
Yuri Hayashi, Ayano Shimamura, Tomoko Ishikawa, Yoko Fujiwara, Ikuyo Ichi
Fatty acid desaturase 2 (FADS2) is responsible for the first desaturation reaction in the synthesis of highly unsaturated fatty acids (HUFAs), such as arachidonic acid (20:4n-6) and eicosapentaenoic acid (20:5n-3), and is involved in Mead acid (20:3n-9) production during essential fatty acid deficiency (EFAD). In this study, an obvious hepatic lipid accumulation was observed in EFAD mice treated with a FADS2 inhibitor. FADS2 inhibition in the EFAD state reduced secretion of very low-density lipoprotein (VLDL) and markedly diminished Mead acid in phosphatidylcholine (PC) in the liver and plasma...
January 15, 2018: Biochemical and Biophysical Research Communications
https://www.readbyqxmd.com/read/29352842/amylin-in-the-insulin-resistance-of-patients-with-rheumatoid-arthritis
#6
Ivan Ferraz-Amaro, Raquel López-Mejias, Beatriz Tejera-Segura, Antonia M de Vera-González, Begoña Ubilla, Jose M Olmos, José Luis Hernández, Miguel Angel González-Gay
OBJECTIVES: Amylin, which is co-secreted with insulin, plays a role in glycemic regulation and is impaired in type 2 diabetes. In the present study we assess, for the first time, the implication of amylin in the development of insulin resistance (IR) in rheumatoid arthritis (RA). METHODS: This was a cross-sectional study involving 361 non-diabetic individuals, 151 patients with RA and 210 sex-matched controls. Insulin, C-peptide, amylin, lipoprotein serum concentrations, and IR indexes by homeostatic model assessment (HOMA2) were evaluated in patients and controls...
January 15, 2018: Clinical and Experimental Rheumatology
https://www.readbyqxmd.com/read/29352211/hdl-nanoparticles-targeting-sonic-hedgehog-subtype-medulloblastoma
#7
Jonathan B Bell, Jonathan S Rink, Frank Eckerdt, Jessica Clymer, Stewart Goldman, C Shad Thaxton, Leonidas C Platanias
Medulloblastoma is the most common paediatric malignant brain cancer and there is a need for new targeted therapeutic approaches to more effectively treat these malignant tumours, which can be divided into four molecular subtypes. Here, we focus on targeting sonic hedgehog (SHH) subtype medulloblastoma, which accounts for approximately 25% of all cases. The SHH subtype relies upon cholesterol signalling for tumour growth and maintenance of tumour-initiating cancer stem cells (CSCs). To target cholesterol signalling, we employed biomimetic high-density lipoprotein nanoparticles (HDL NPs) which bind to the HDL receptor, scavenger receptor type B-1 (SCARB1), depriving cells of natural HDL and their cholesterol cargo...
January 19, 2018: Scientific Reports
https://www.readbyqxmd.com/read/29351922/activation-of-constitutive-androstane-receptor-ameliorates-renal-ischemia-reperfusion-induced-liver-and-kidney-injury
#8
You-Jin Choi, Dong Zhou, Anne Barbosa, Yongdong Niu, Xiudong Guan, Meishu Xu, Songrong Ren, Thomas Nolin, Yiuhua Liu, Wen Xie
Acute kidney injury (AKI) is associate with high mortality. Despite the evidence of AKI-induced distant organ injury, a relationship between AKI and liver injury has not been clearly established. The goal of this study is to investigate whether renal ischemia-reperfusion (IR) can affect liver pathophysiology. We showed that renal IR in mice induced fatty liver and compromised liver function through the down-regulation of constitutive androstane receptor (CAR; -90.4%) and inhibition of hepatic very low-density lipoprotein-triglyceride (VLDL-TG) secretion (-28...
January 19, 2018: Molecular Pharmacology
https://www.readbyqxmd.com/read/29351856/high-density-lipoprotein-with-apolipoprotein-c-iii-is-associated-with-carotid-intima-media-thickness-among-generally-healthy-individuals
#9
Rain Yamamoto, Frank M Sacks, Frank B Hu, Bernard Rosner, Jeremy D Furtado, Sarah A Aroner, Ele Ferrannini, Simona Baldi, Michaela Kozakova, Beverley Balkau, Andrea Natali, Majken K Jensen
BACKGROUND AND AIMS: About 6-7% of high density lipoprotein (HDL) has a protein called apolipoprotein (apo) C-III that regulates lipoprotein metabolism and can provoke an inflammatory response. HDL without apoC-III is inversely associated with coronary heart disease (CHD), whereas HDL with apoC-III is directly associated with CHD. We investigated how the presence of apoC-III affects the association between HDL and early stages of atherosclerosis measured as carotid intima-media thickness (cIMT)...
January 2, 2018: Atherosclerosis
https://www.readbyqxmd.com/read/29351469/inhibition-of-mtor-protects-the-blood-brain-barrier-in-models-of-alzheimer-s-disease-and-vascular-cognitive-impairment
#10
Candice E Van Skike, Jordan B Jahrling, Angela B Olson, Naomi L Sayre, Stacy A Hussong, Zoltan I Ungvari, James D Lechleiter, Veronica Galvan
An intact blood-brain barrier (BBB) limits entry of pro-inflammatory and neurotoxic blood-derived factors into the brain parenchyma. The BBB is damaged in Alzheimer's disease (AD), which contributes significantly to the progression of AD pathologies and cognitive decline. However, the mechanisms underlying BBB breakdown in AD remain elusive and no interventions are available for treatment or prevention. We and others recently established that inhibition of the mammalian/mechanistic target of rapamycin (mTOR) pathway with rapamycin yields significant neuroprotective effects, improving cerebrovascular and cognitive function in mouse models of AD...
December 22, 2017: American Journal of Physiology. Heart and Circulatory Physiology
https://www.readbyqxmd.com/read/29351106/the-role-of-patient-registries-for-rare-genetic-lipid-disorders
#11
David M Ng, Amanda J Hooper, Matthew I Bellgard, John R Burnett
PURPOSE OF REVIEW: We review the role, utility and current status of patient registries for rare genetic lipid disorders. RECENT FINDINGS: The creation and maintenance of rare genetic lipid disorder patient registries is critical for disease monitoring, improving clinical best practice, facilitating research and enabling the development of novel therapeutics. An open-source disease registry platform, termed the Rare Disease Registry Framework, has been developed, optimized and deployed for homozygous familial hypercholesterolemia...
January 17, 2018: Current Opinion in Lipidology
https://www.readbyqxmd.com/read/29350757/hepatoprotective-effects-of-sophoricoside-against-fructose-induced-liver-injury-via-regulating-lipid-metabolism-oxidation-and-inflammation-in-mice
#12
Wenfeng Li, Yalong Lu
The dried fruit of Sophora japonica L. is a traditional Chinese herb tea rich in sophoricoside that is an isoflavone glycoside. The aim of current study was to investigate the hepatic protective effect of sophoricoside in high fructose (HF) diet fed mice. Healthy male mice were fed 30% fructose water and treated 80 and 160 mg/kg·bw sophoricoside continuously for 8 wk. Our data showed that administration of sophoricoside at 80 and 160 mg/kg·bw observably decreased the body weight and liver weight in HF-fed mice...
January 19, 2018: Journal of Food Science
https://www.readbyqxmd.com/read/29350676/an-increase-in-high%C3%A2-density-lipoprotein-cholesterol-concentration-after-initiation-of-insulin-treatment-is-dose%C3%A2-dependent-in-newly-diagnosed-type-1-diabetes-the-results-of-the-inlipodiab1-study
#13
Aleksandra Cieluch, Aleksandra Uruska, Agata Grzelka, Dorota Zozulińska-Ziółkiewicz
No abstract text is available yet for this article.
January 19, 2018: Polish Archives of Internal Medicine
https://www.readbyqxmd.com/read/29350661/retrospective-analysis-of-the-effects-of-a-highly-standardized-mixture-of-berberis-aristata-silybum-marianum-and-monacolins-k-and-ka-in-diabetic-patients-with-dyslipidemia
#14
Francesco Di Pierro, Pietro Putignano, Nicola Villanova
BACKGROUND: Berberine, an alkaloid with both glucose- and cholesterol-lowering action, is also characterized by an anti-diarrheal effect. Consequently, berberine-based therapies are recommended for diabetic patients with irritable bowel syndrome (IBS) or gut discomfort caused by metformin. AIM: As the anti-glycemic and cholesterol-lowering action of berberine is improved by co-administration with P-glycoprotein inhibitors and naturally derived statins, we have analyzed the effect of the food supplement Berberol®K (hereafter referred to as BSM) containing, berberine, silymarin, and a highly standardized red yeast rice containing monacolins K and KA in the ratio 1:1 but no secondary monacolins, dehydromonacolins, or citrinin (Monakopure™-K20)...
January 16, 2018: Acta Bio-medica: Atenei Parmensis
https://www.readbyqxmd.com/read/29350379/metabolic-syndrome-in-hiv-infected-adults-in-poland
#15
Magdalena Rogalska-Płońska, Anna Grzeszczuk, Paweł Rogalski, Mariusz Łucejko, Robert Flisiak
BACKGROUND: Metabolic syndrome (MS) is usually diagnosed based on presence of abdominal obesity, elevated blood pressure, elevated fasting plasma glucose, high serum triglycerides (TG) and low high-density lipoprotein levels (HDL). Whether HIV is associated with a higher prevalence of metabolic syndrome than general population remains unclear. AIM: Aim of the study was to determine the incidence of metabolic syndrome in the population of HIV infected adults and its association with clinical, virological and biochemical features...
January 19, 2018: Kardiologia Polska
https://www.readbyqxmd.com/read/29349446/ameliorative-role-of-camel-whey-protein-and-rosuvastatin-on-induced-dyslipidemia-in-mice
#16
Nashwa Ahmed El-Shinnawy, Sahar Sobhy Abd Elhalem, Nawal Zakaria Haggag, Gamal Badr
The incidence of obesity is rapidly increasing throughout the world. Dyslipidemia is a major risk factor for a number of chronic diseases, including diabetes and cardiovascular diseases. This work presents a novel approach to study the activity of camel whey protein (WP) with antioxidant and anti-inflammatory properties as a cheap dietary protein substance extracted from camel milk to produce satiety and help in building muscles. Mice model suffering from dyslipidemia as a result of feeding on high fat-cholesterol diet for 8 weeks were administrated with either camel WP and/or rosuvastatin for 4 weeks...
January 19, 2018: Food & Function
https://www.readbyqxmd.com/read/29349100/vitamin-d-deficiency-associated-with-markers-of-cardiovascular-disease-in-children-with-obesity
#17
Marisa Censani, Hoda T Hammad, Paul J Christos, Tiffany Schumaker
Adult studies have reported associations of low 25-hydroxyvitamin D (25OHD) with dyslipidemia and cardiovascular disease; however, there are scarce pediatric data regarding relationships between vitamin D status and specific lipid markers affecting cardiovascular risk. In this cross-sectional study of children evaluated at university-based pediatric endocrinology clinics, 178 patients meeting criteria for overweight or obesity had 25OHD levels assessed over a 2-year period; 60 of 178 had non-HDL (high-density lipoprotein) cholesterol and fasting lipid parameters performed...
2018: Global Pediatric Health
https://www.readbyqxmd.com/read/29348840/the-prevalence-of-and-risk-factors-for-diabetes-mellitus-and-impaired-glucose-tolerance-among-tibetans-in-china-a-cross-sectional-study
#18
Shaopeng Xu, Qing Wang, Jie Liu, Bo Bian, Xuefang Yu, Xiangdong Yu, Xianjia Ning, Jinghua Wang
The prevalence of diabetes mellitus (DM) and impaired glucose tolerance (IGT) has increased worldwide, although their prevalence and determinants among Tibetans are currently unknown. We thus aimed to explore the prevalence of and risk factors for DM and IGT among Tibetans in China. In 2011, 1659 Tibetan adults (aged ≥ 18 years) from Changdu, China, were recruited to this cross-sectional study. They completed a questionnaire and underwent physical examinations and laboratory testing to assess risk factors for DM and IGT...
December 22, 2017: Oncotarget
https://www.readbyqxmd.com/read/29348120/apoc3-loss-of-function-mutations-remnant-cholesterol-low-density-lipoprotein-cholesterol-and-cardiovascular-risk-mediation-and-meta-analyses-of-137-895-individuals
#19
Anders B Wulff, Børge G Nordestgaard, Anne Tybjærg-Hansen
OBJECTIVE: Loss-of-function mutations in APOC3 associate with low remnant cholesterol levels and low risk of ischemic vascular disease (IVD). Because some studies show an additional association with low levels of low-density lipoprotein cholesterol (LDL-C), low LDL-C may explain the low risk of IVD in APOC3 loss-of-function heterozygotes. We tested to what extent the low risk of IVD in APOC3 loss-of-function heterozygotes is mediated by low plasma remnant cholesterol and LDL-C. APPROACH AND RESULTS: In APOC3 loss-of-function heterozygotes versus noncarriers, we first determined remnant cholesterol and LDL-C levels in meta-analyses of 137 895 individuals...
January 18, 2018: Arteriosclerosis, Thrombosis, and Vascular Biology
https://www.readbyqxmd.com/read/29348089/a-study-of-serological-markers-and-lipid-profile-in-non-alcoholic-liver-cirrhosis-patients
#20
Sadaf Khan, Siddiqua Jamal
Cirrhosis is the end result of chronic liver damage, associated with altered serum biomarkers and lipid profile. However, only few studies regarding serum biomarkers and plasma lipid profile in non-alcoholic liver cirrhosis subjects have been undertaken in Pakistan. This study aimed to evaluate the degree of alterations of tumor markers and lipid profile in liver cirrhosis patients and in normal healthy individuals. Levels of serological markers and plasma lipid pattern was measured in liver cirrhosis patients and in sex and age matched normal healthy individuals (n=46)...
January 2018: Pakistan Journal of Pharmaceutical Sciences
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