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Hypercholesterolemia

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https://www.readbyqxmd.com/read/28938515/regulation-of-hepatic-hydroxy-methyl-glutarate-coa-reductase-for-controlling-hypercholesterolemia-in-rats
#1
Abeer A Khamis, Afrah F Salama, Marwa E Kenawy, Tarek M Mohamed
Hypercholesterolemia is a major risk factor upon developing cardiovascular diseases. This study is aiming to investigate the inhibition role of quercetin on hydroxy methyl glutarate - CoA reductase activity and its gene for attenuating hypercholesterolemia. The kinetic characteristics of HMG-CoA reductase activity were evaluated on extracellular rat liver microsomes. For studying the effect of quercetin by inducing hypercholesterolemia rats by Tyloxapol (i.v.). In addition, rats were treated with different doses of quercetin according to the inhibition constant of this inhibitor...
September 18, 2017: Biomedicine & Pharmacotherapy, Biomédecine & Pharmacothérapie
https://www.readbyqxmd.com/read/28938444/lack-of-lrp5-signaling-in-osteoblasts-sensitizes-male-mice-to-diet-induced-disturbances-in-glucose-metabolism
#2
Soohyun P Kim, Julie L Frey, Zhu Li, Brian C Goh, Ryan C Riddle
Wnt signaling through the Lrp5 co-receptor regulates osteoblast maturation, matrix mineralization, and intermediary metabolism. In the mature osteoblast, signals downstream of Lrp5 are required for normal long-chain fatty acid β-oxidation and mice rendered deficient for this co-receptor in osteoblasts and osteocytes accumulate body fat with elevated serum lipid levels, but retain normal insulin sensitivity. In this study, we challenged Lrp5 mutant mice with a high fat diet to determine if they are more susceptible to diet-induced disturbances in glucose homeostasis...
September 11, 2017: Endocrinology
https://www.readbyqxmd.com/read/28936788/isorhamnetin-derivatives-and-piscidic-acid-for-hypercholesterolemia-cholesterol-permeability-hmg-coa-reductase-inhibition-and-docking-studies
#3
Asma Ressaissi, Nebil Attia, Pedro Luis Falé, Rita Pacheco, Bruno L Victor, Miguel Machuqueiro, Maria Luísa M Serralheiro
Bioactive compounds, such as isorhamnetin and piscidic acid, were obtained from decoctions of cladodes (stem pads from Opuntia ficus-indica). The effect of these phenolic compounds, in a fiber-free extract, were evaluated as inhibitors of cholesterol permeation through a Caco-2 cell monolayer and as 3-hydroxy-3-methylglutaryl coenzyme A reductase inhibitor. A reduction of 38% in cholesterol permeation through the Caco-2 cell monolayer was obtained, and the phenolic compounds all permeated between 6 and 9%. A mixture of these compounds showed an IC50 of 20...
September 21, 2017: Archives of Pharmacal Research
https://www.readbyqxmd.com/read/28935756/perinatal-hypercholesterolemia-exacerbates-atherosclerosis-lesions-in-offspring-by-altering-metabolism-of-trimethylamine-n-oxide-and-bile-acids
#4
Charlotte Trenteseaux, Anh-Thu Gaston, Audrey Aguesse, Guillaume Poupeau, Pierre de Coppet, Ramaroson Andriantsitohaina, Jamila Laschet, Valérie Amarger, Michel Krempf, Estelle Nobecourt-Dupuy, Khadija Ouguerram
OBJECTIVE: Experimental studies suggest that maternal hypercholesterolemia may be relevant for the early onset of cardiovascular disease in offspring. We investigated the effect of perinatal hypercholesterolemia on the atherosclerosis development in the offspring of apolipoprotein E-deficient mice and the underlying mechanism. APPROACH AND RESULTS: Atherosclerosis and related parameters were studied in adult male or female apolipoprotein E-deficient mice offspring from either normocholesterolemic or hypercholesterolemic mothers and normocholesterolemic fathers...
September 21, 2017: Arteriosclerosis, Thrombosis, and Vascular Biology
https://www.readbyqxmd.com/read/28935567/lactobacillus-fermentum-ftdc-8312-combats-hypercholesterolemia-via-alteration-of-gut-microbiota
#5
Huey-Shi Lye, Tamotsu Kato, Wai-Yee Low, Todd D Taylor, Tulika Prakash, Lee-Ching Lew, Hiroshi Ohno, Min-Tze Liong
In this study, hypercholesterolemic mice fed with Lactobacillus fermentum FTDC 8312 after a seven-week feeding trial showed a reduction in serum total cholesterol (TC) levels, accompanied by a decrease in serum low-density lipoprotein cholesterol (LDL-C) levels, an increase in serum high-density lipoprotein cholesterol (HDL-C) levels, and a decreased ratio of apoB100:apoA1 when compared to those fed with control or a type strain, L. fermentum JCM 1173. These have contributed to a decrease in atherogenic indices (TC/HDL-C) of mice on the FTDC 8312 diet...
September 18, 2017: Journal of Biotechnology
https://www.readbyqxmd.com/read/28933629/ezetimibe-ameliorates-steatohepatitis-via-amp-activated-protein-kinase-tfeb-mediated-activation-of-autophagy-and-nlrp3-inflammasome-inhibition
#6
Soo Hyun Kim, Gyuri Kim, Dai Hoon Han, Milim Lee, Irene Kim, Bohkyung Kim, Kook Hwan Kim, Young-Mi Song, Jeong Eun Yoo, Hye Jin Wang, Soo Han Bae, Yong-Ho Lee, Byung-Wan Lee, Eun Seok Kang, Bong-Soo Cha, Myung-Shik Lee
Impairment in macroautophagy/autophagy flux and inflammasome activation are common characteristics of nonalcoholic steatohepatitis (NASH). Considering the lack of approved agents for treating NASH, drugs that can enhance autophagy and modulate inflammasome pathways may be beneficial. Here, we investigated the novel mechanism of ezetimibe, a widely prescribed drug for hypercholesterolemia, as a therapeutic option for ameliorating NASH. Human liver samples with steatosis and NASH were analyzed. For in vitro studies of autophagy and inflammasomes, primary mouse hepatocytes, human hepatoma cells, mouse embryonic fibroblasts with Ampk or Tsc2 knockout, and human or primary mouse macrophages were treated with ezetimibe and palmitate...
September 21, 2017: Autophagy
https://www.readbyqxmd.com/read/28932900/-68ga-pentixafor-pet-mri-for-the-detection-of-chemokine-receptor-4-expression-in-atherosclerotic-plaques
#7
Xiang Li, Daniel Heber, Tatjana Leike, Dietrich Beitzke, Xia Lu, Xiaoli Zhang, Yongxiang Wei, Markus Mitterhauser, Wolfgang Wadsak, Saskia Kropf, Hans J Wester, Christian Loewe, Marcus Hacker, Alexander R Haug
PURPOSE: The expression of chemokine receptor type 4 (CXCR4) was found co-localized with macrophages on the atherosclerotic vessel wall and participated in the initial emigration of leukocytes. Gallium-68 [(68)Ga]Pentixafor has recently been introduced for the imaging of atherosclerosis by targeting CXCR4. We sought to evaluate human atherosclerotic lesions using [(68)Ga]Pentixafor PET/MRI. METHODS: Thirty-eight oncology patients underwent [(68)Ga]Pentixafor PET/MR imaging at baseline...
September 21, 2017: European Journal of Nuclear Medicine and Molecular Imaging
https://www.readbyqxmd.com/read/28932124/marketed-drugs-used-for-the-management-of-hypercholesterolemia-as-anticancer-armament
#8
REVIEW
Panagiota Papanagnou, Theodora Stivarou, Ioannis Papageorgiou, Georgios E Papadopoulos, Anastasios Pappas
The design of novel pharmacologic agents as well as their approval for sale in markets all over the world is a tedious and pricey process. Inevitably, oncologic patients commonly experience unwanted effects of new anticancer drugs, while the acquisition of clinical experience for these drugs is largely based on doctor-patient partnership which is not always effective. The repositioning of marketed non-antineoplastic drugs that hopefully exhibit anticancer properties into the field of oncology is a challenging option that gains ground and attracts preclinical and clinical research in an effort to override all these hindrances and minimize the risk for reduced efficacy and/or personalized toxicity...
2017: OncoTargets and Therapy
https://www.readbyqxmd.com/read/28930746/early-assessment-of-the-risk-factors-for-diabetic-retinopathy-can-reduce-the-risk-of-peripheral-arterial-and-cardiovascular-diseases-in-type-2-diabetes
#9
Juan Tang, Tao Li, Pinhong Li, Yuefei Ma, Momo Liu, Qiaoyun Shan, Fengqi Guo, Ting Zhou, Qianping Wei
BACKGROUNDS: There is still a lack of consensus about how to assess the risk of peripheral arterial disease (PAD) and cardiovascular disease (CVD) in patients with diabetic retinopathy (DR). AIMS: We investigated the risk factors for DR and their association with PAD and CVD in patients with type 2 diabetes (T2D). METHODS: A total of 1,421 patients diagnosed with T2D participated in this study. DR stages were classified as non-DR, nonproliferative DR (NPDR), or proliferative DR (PDR)...
September 21, 2017: Ophthalmic Research
https://www.readbyqxmd.com/read/28927716/the-effects-of-lifestyle-modification-and-statin-therapy-on-the-circulatory-markers-for-vascular-risk-in-patients-with-epilepsy
#10
Dong Wook Kim, Hyun Kyung Kim, Eun-Kee Bae
Although long-term therapy with antiepileptic drugs can increase the risk of vascular diseases, there have been little attempts to reduce the increased vascular risk in patients with epilepsy. We conducted a prospective longitudinal study to assess the effects of lifestyle modification and 3-hydroxy-3-methylglutaryl-coenzyme A (HMG-CoA) reductase inhibitor (statin) therapy on the increased circulatory markers for vascular risk in patients with epilepsy. We recruited patients with increased vascular risk such as a history of vascular events or hypercholesterolemia, and they decided whether to be treated with statin or just to modify their lifestyle...
September 15, 2017: Epilepsy & Behavior: E&B
https://www.readbyqxmd.com/read/28926730/impact-of-evolocumab-treatment-on-low-density-lipoprotein-cholesterol-levels-in-heterozygous-familial-hypercholesterolemic-patients-withdrawing-from-regular-apheresis
#11
Masa-Aki Kawashiri, Atsushi Nohara, Toshinori Higashikata, Hayato Tada, Chiaki Nakanishi, Hirofumi Okada, Tetsuo Konno, Kenji Sakata, Kenshi Hayashi, Akihiro Inazu, Hiroshi Mabuchi, Masakazu Yamagishi
BACKGROUND AND AIMS: Low-density lipoprotein (LDL) apheresis has been used to treat refractory hyperlipidemia such as familial hypercholesterolemia (FH). Evolocumab, a proprotein convertase subtilisin/kexin type 9 (PCSK9) inhibitor used in clinical settings, can reduce LDL cholesterol (LDL-C) levels by >70%. Therefore, this study aimed to assess the impact of evolocumab on withdrawal from regular LDL apheresis in patients with heterozygous FH (HeFH). METHODS: Eleven patients with HeFH undergoing biweekly LDL apheresis were enrolled and were subsequently switched to a biweekly subcutaneous injection of 140 mg of evolocumab...
September 9, 2017: Atherosclerosis
https://www.readbyqxmd.com/read/28926478/characterization-of-spontaneous-hydrocephalus-development-in-the-young-atherosclerosis-prone-mice
#12
Chuanguo Liu, Guorong Li, Pingping Wang, Yan Wang, Jie Pan
Little has been reported on whether abnormal lipid metabolism affects hydrocephalus, although congenital malformations and infectious diseases are major causal factors for hydrocephalus development. In a study on the pathogenesis of atherogenesis in mice, we unexpectedly discovered that hydrocephalus occurred in partial apolipoptotein E (apoE) and low-density lipoprotein receptor (LDLR) double-knockout (apoE/LDLR) mice fed either chow or a high-fat and high-cholesterol diet between the ages of 4 and 12 weeks...
September 18, 2017: Neuroreport
https://www.readbyqxmd.com/read/28925748/the-effect-of-lomitapide-on-cardiovascular-outcome-measures-in-homozygous-familial-hypercholesterolemia-a-modelling-analysis
#13
Robert Leipold, Frederick Raal, Jack Ishak, Kees Hovingh, Helen Phillips
Background Patients with homozygous familial hypercholesterolemia are at high risk of cardiovascular disease due to high low-density lipoprotein (LDL)-cholesterol levels. Cardiovascular disease outcome studies are impossible to conduct, due to the rarity of homozygous familial hypercholesterolemia. We modelled the potential efficacy of lomitapide, a microsomal transfer protein inhibitor, on major adverse cardiovascular events (MACEs) and survival. Design We calculated the effect on cardiovascular outcomes of a 38% plasma LDL-cholesterol reduction induced by lomitapide...
January 1, 2017: European Journal of Preventive Cardiology
https://www.readbyqxmd.com/read/28922188/new-insights-into-the-role-of-glycosylation-in-lipoprotein-metabolism
#14
Marjolein A W van den Boogert, Daniel J Rader, Adriaan G Holleboom
PURPOSE OF REVIEW: Human genetics has provided new insights into the role of protein glycosylation in regulating lipoprotein metabolism. Here we review these new developments and discuss the biological insights they provide. RECENT FINDINGS: Case descriptions of patients with congenital defects in N-glycosylation (CDG-I) frequently describe a distinct hypocholesterolemia in these rare multisystem clinical syndromes. Two novel CDGs with disturbed Golgi homeostasis and trafficking defects result in mixed glycosylation disorders, hepatic steatosis and hypercholesterolemia...
September 15, 2017: Current Opinion in Lipidology
https://www.readbyqxmd.com/read/28922021/pharmacokinetic-drug-evaluation-of-ezetimibe-simvastatin-for-the-treatment-of-hypercholesterolemia
#15
Marilisa Bove, Federica Fogacci, Arrigo Cicero
-Introduction: Cholesterol lowering treatment is mainly based on statins eventually associated to adjunctive drugs of different class such as ezetimibe. In the present review, we analysed the pharmacokinetics, efficacy and safety of ezetimibe+simvastatin drug association. -Areas covered: The bio-equivalence of ezetimibe and simvastatin when co-administrated in separate tablets or combined in a single pill is well documented. Ezetimibe is absorbed in small intestine, reaching peak plasma concentrations in 4-12 hours, with a plasma half-life of 22 hours...
September 18, 2017: Expert Opinion on Drug Metabolism & Toxicology
https://www.readbyqxmd.com/read/28919772/anti-pcsk9-antibodies-for-the-treatment-of-heterozygous-familial-hypercholesterolemia-patient-selection-and-perspectives
#16
REVIEW
Alberico Luigi Catapano, Angela Pirillo, Giuseppe Danilo Norata
Heterozygous familial hypercholesterolemia (FH) is a genetic disorder characterized by high low-density lipoprotein cholesterol levels from birth, which exposes the arteries to high levels of atherogenic lipoproteins lifelong and results in a significantly increased risk of premature cardiovascular events. The diagnosis of FH, followed by an appropriate and early treatment is critical to reduce the cardiovascular burden in this population. Phase I-III clinical trials showed the benefit of proprotein convertase subtilisin kexin 9 inhibitors, both alirocumab and evolocumab, in these patients with an average low-density lipoprotein cholesterol reduction ranging from -40% to -60%...
2017: Vascular Health and Risk Management
https://www.readbyqxmd.com/read/28919240/single-nucleotide-variants-associated-with-polygenic-hypercholesterolemia-in-families-diagnosed-clinically-with-familial-hypercholesterolemia
#17
Itziar Lamiquiz-Moneo, María Rosario Pérez-Ruiz, Estíbaliz Jarauta, María Teresa Tejedor, Ana M Bea, Rocío Mateo-Gallego, Sofía Pérez-Calahorra, Lucía Baila-Rueda, Victoria Marco-Benedí, Isabel de Castro-Orós, Ana Cenarro, Fernando Civeira
INTRODUCTION AND OBJECTIVES: Approximately 20% to 40% of clinically defined familial hypercholesterolemia cases do not show a causative mutation in candidate genes, and some of them may have a polygenic origin. A cholesterol gene risk score for the diagnosis of polygenic hypercholesterolemia has been demonstrated to be valuable to differentiate polygenic and monogenic hypercholesterolemia. The aim of this study was to determine the contribution to low-density lipoprotein cholesterol (LDL-C) of the single nucleotide variants associated with polygenic hypercholesterolemia in probands with genetic hypercholesterolemia without mutations in candidate genes (nonfamilial hypercholesterolemia genetic hypercholesterolemia) and the genetic score in cascade screening in their family members...
September 14, 2017: Revista Española de Cardiología
https://www.readbyqxmd.com/read/28918614/modifiable-co-morbidities-trends-during-hospital-admissions-for-obesity-in-france-2009-2014
#18
Pierre Nanyan
Obesity is a growing public health problem in France, but modifiable co-morbidities in obese patients during their hospital admissions excluding bariatric surgery are lacking. Data were extracted from the French national hospital discharge database. Data on patient admissions, age, gender, and length of stay were extracted by selecting any stay coded primary as obesity. Obesity was defined as body mass index (BMI) between 30-39 kg/m², and morbid obesity as BMI≥40 kg/m². Only modifiable co-morbidities frequently diagnosed during the 6-year period with a rate≥3% were chosen...
July 2017: Acta Medica Iranica
https://www.readbyqxmd.com/read/28918428/modification-of-cardiovascular-pharmacotherapy-in-palliative-care-patients-with-cancer-narrative-review
#19
Tomasz Pasierski
Palliative care cancer patients are treated with many drugs especially at the end of life. Limiting of polypharmacy a decreases the risk of associated adverse effects, medical errors and harmful drug interactions The time lag to benefit of many medications used for cardiovascular diseases or risk factors like hypertension, hypercholesterolemia is frequently longer than palliative care cancer patient's life expectancy. It is ethically appropriate to modify, even to discontinue cardiovascular pharmacotherapy when there is no prospect of benefit...
September 13, 2017: Polish Archives of Internal Medicine
https://www.readbyqxmd.com/read/28916377/clinical-and-molecular-characterization-of-two-chinese-patients-with-type-2-congenital-generalized-lipodystrophy
#20
Ruimin Chen, Xin Yuan, Jian Wang, Ying Zhang
BACKGROUND: Type 2 congenital generalized lipodystrophy (CGL2, OMIM 269700) is a rare autosomal recessive disease, characterized by the generalized absence of adipose tissue at birth or in early infancy. Pathogenic variants in BSCL2 gene have been reported to be responsible for CGL2. The aim of this study is to analyze the clinical and genetic characteristics of two Chinese patients with CGL2, and with particular focus on the BSCL2 gene sequence variants. METHODS: Medical history, clinical manifestations, physical examination, laboratory data, and ultrasonography findings were analyzed for the two patients with CGL2...
September 12, 2017: Gene
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