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https://www.readbyqxmd.com/read/28819865/melatonin-mitochondria-and-the-metabolic-syndrome
#1
REVIEW
Daniel P Cardinali, Daniel E Vigo
A number of risk factors for cardiovascular disease including hyperinsulinemia, glucose intolerance, dyslipidemia, obesity, and elevated blood pressure are collectively known as metabolic syndrome (MS). Since mitochondrial activity is modulated by the availability of energy in cells, the disruption of key regulators of metabolism in MS not only affects the activity of mitochondria but also their dynamics and turnover. Therefore, a link of MS with mitochondrial dysfunction has been suspected since long. As a chronobiotic/cytoprotective agent, melatonin has a special place in prevention and treatment of MS...
August 17, 2017: Cellular and Molecular Life Sciences: CMLS
https://www.readbyqxmd.com/read/28819016/a-syndromic-extreme-insulin-resistance-caused-by-biallelic-poc1a-mutations-in-exon-10
#2
Elisa Giorgio, Elisa Rubino, Alessandro Bruselles, Simone Pizzi, Innocenzo Rainero, Sergio Duca, Fabio Sirchia, Barbara Pasini, Marco Tartaglia, Alfredo Brusco
POC1A encodes a protein with a role in centriole assembly and stability, and in ciliogenesis. Biallelic loss of function mutations affecting POC1A cause SOFT syndrome, an ultra-rare condition characterized by short stature, onychodysplasia, facial dysmorphism and hypotrichosis. Using exome sequencing, we identified a homozygous frameshift mutation (c.1047_1048dupC; p.G337Rfs*25) in a patient presenting with short stature, facial hirsutism, alopecia, dyslipidemia and extreme insulin resistance. The truncating variant affected exon 10, which is retained in only two of the three POC1A mature RNAs, due to alternative processing of the transcript...
August 17, 2017: European Journal of Endocrinology
https://www.readbyqxmd.com/read/28814891/diabetes-and-dyslipidemia-characterizing-lipoprotein-metabolism
#3
REVIEW
G H Tomkin, D Owens
Premature atherosclerosis in diabetes accounts for much of the decreased life span. New treatments have reduced this risk considerably. This review explores the relationship among the disturbances in glucose, lipid, and bile salt metabolic pathways that occur in diabetes. In particular, excess nutrient intake and starvation have major metabolic effects, which have allowed us new insights into the disturbance that occurs in diabetes. Metabolic regulators such as the forkhead transcription factors, the farnesyl X transcription factors, and the fibroblast growth factors have become important players in our understanding of the dysregulation of metabolism in diabetes and overnutrition...
2017: Diabetes, Metabolic Syndrome and Obesity: Targets and Therapy
https://www.readbyqxmd.com/read/28814665/fatty-acid-oxidation-by-the-osteoblast-is-required-for-normal-bone-acquisition-in-a-sex-and-diet-dependent-manner
#4
Soohyun P Kim, Zhu Li, Meredith L Zoch, Julie L Frey, Caitlyn E Bowman, Priyanka Kushwaha, Kathleen A Ryan, Brian C Goh, Susanna Scafidi, Julie E Pickett, Marie-Claude Faugere, Erin E Kershaw, Daniel L J Thorek, Thomas L Clemens, Michael J Wolfgang, Ryan C Riddle
Postnatal bone formation is influenced by nutritional status and compromised by disturbances in metabolism. The oxidation of dietary lipids represents a critical source of ATP for many cells but has been poorly studied in the skeleton, where the prevailing view is that glucose is the primary energy source. Here, we examined fatty acid uptake by bone and probed the requirement for fatty acid catabolism during bone formation by specifically disrupting the expression of carnitine palmitoyltransferase 2 (Cpt2), an obligate enzyme in fatty acid oxidation, in osteoblasts and osteocytes...
August 17, 2017: JCI Insight
https://www.readbyqxmd.com/read/28807460/metabolic-syndrome-cluster-does-not-provide-incremental-prognostic-information-in-patients-with-stable-cardiovascular-disease-a-post-hoc-analysis-of-the-aim-high-trial
#5
Radmila Lyubarova, Jennifer G Robinson, Michael Miller, Debra L Simmons, Ping Xu, Beth L Abramson, Marshall B Elam, Todd M Brown, Ruth McBride, Jerome L Fleg, Patrice Desvigne-Nickens, Woubeshet Ayenew, William E Boden
BACKGROUND: Metabolic syndrome (MS) is a well-known risk factor for the development of cardiovascular (CV) disease; yet, controversy persists whether it adds incremental prognostic value in patients with established CV disease. OBJECTIVES: This study was performed to determine if MS is associated with worse CV outcomes in patients with established CV disease treated intensively with statins. METHODS: We performed a post hoc analysis of the Atherothrombosis Intervention in Metabolic Syndrome with Low HDL/High Triglycerides and Impact on Global Health Outcomes trial, in which patients with established CV disease and atherogenic dyslipidemia (n = 3414) were randomly assigned to receive extended release niacin or placebo during a mean 36-month follow-up, to assess whether the presence of MS or the number of MS components contributed to CV outcomes...
July 5, 2017: Journal of Clinical Lipidology
https://www.readbyqxmd.com/read/28807458/caveolin-3-deficiency-myopathy-associated-with-dyslipidemia-treatment-challenges-and-possible-pathophysiological-association
#6
Daiana Ibarretxe, Joan Pellejà, Nicolau Ortiz, Luis Masana
We report the case of a patient treated at the lipid clinic because of high cholesterol levels with consistently elevated creatine kinase concentrations that precluded statin treatment. Electromyography showed a rippling muscle disease pattern. A muscle biopsy confirmed caveolin 3 deficiency, and a missense mutation in the CAV3 gene was identified. The patient could be properly managed with ezetimibe and cholestyramine, which reduced the low-density lipoprotein cholesterol by 30%. He remains asymptomatic after 10 years of follow-up...
August 1, 2017: Journal of Clinical Lipidology
https://www.readbyqxmd.com/read/28807220/health-characteristics-of-heart-transplant-recipients-surviving-into-their-80s
#7
Deborah R Tabachnick, Megan E Bowen, Josef Stehlik, Abdallah G Kfoury, William T Caine, Craig H Selzman, Stephen H McKellar
BACKGROUND: Heart transplantation (HTx) is the preferred treatment for patients with end-stage heart failure and has been successful for >30 y. The clinical course of recipients at the extreme of age is unknown. We reviewed our experience to determine the overall health and prevalence of Tx-related medical problems for recipients in their ninth decade. METHODS: We reviewed the UCTP experience from 1985 to present to identify patients who survived into their 80s and matched (1:1) with other recipients for gender and age at HTx, but did not survive to ≥80 y...
August 2017: Journal of Surgical Research
https://www.readbyqxmd.com/read/28806968/cardamom-powder-supplementation-prevents-obesity-improves-glucose-intolerance-inflammation-and-oxidative-stress-in-liver-of-high-carbohydrate-high-fat-diet-induced-obese-rats
#8
Md Mizanur Rahman, Mohammad Nazmul Alam, Anayt Ulla, Farzana Akther Sumi, Nusrat Subhan, Trisha Khan, Bishwajit Sikder, Hemayet Hossain, Hasan Mahmud Reza, Md Ashraful Alam
BACKGROUND: Cardamom is a well-known spice in Indian subcontinent, used in culinary and traditional medicine practices since ancient times. The current investigation was untaken to evaluate the potential benefit of cardamom powder supplementation in high carbohydrate high fat (HCHF) diet induced obese rats. METHOD: Male Wistar rats (28 rats) were divided into four different groups such as Control, Control + cardamom, HCHF, HCHF + cardamom. High carbohydrate and high fat (HCHF) diet was prepared in our laboratory...
August 14, 2017: Lipids in Health and Disease
https://www.readbyqxmd.com/read/28806738/partial-igf-1-deficiency-is-sufficient-to-reduce-heart-contractibility-angiotensin-ii-sensibility-and-alter-gene-expression-of-structural-and-functional-cardiac-proteins
#9
José Luis González-Guerra, Inma Castilla-Cortazar, Gabriel A Aguirre, Úrsula Muñoz, Irene Martín-Estal, Elena Ávila-Gallego, Miriam Granado, Juan E Puche, Ángel Luis García-Villalón
Circulating levels of IGF-1 may decrease under several circumstances like ageing, metabolic syndrome, and advanced cirrhosis. This reduction is associated with insulin resistance, dyslipidemia, progression to type 2 diabetes, and increased risk for cardiovascular diseases. However, underlying mechanisms between IGF-1 deficiency and cardiovascular disease remain elusive. The specific aim of the present work was to study whether the partial IGF-1 deficiency influences heart and/or coronary circulation, comparing vasoactive factors before and after of ischemia-reperfusion (I/R)...
2017: PloS One
https://www.readbyqxmd.com/read/28804621/development-of-gene-polymorphisms-in-meditators-of-nonalcoholic-fatty-liver-disease
#10
Chun Wang, Jianping Gong, Hao Wu
Nonalcoholic fatty liver disease (NAFLD) is the most prevalent liver disease worldwide, the morbidity of which closely correlates with diversity of ethnicity, minority, family and location. Its histology spans from simple steatosis, to nonalcoholic steatohepatitis, which ultimately results in fibrosis, cirrhosis and hepatocellular carcinoma. The accelerating prevalence of NAFLD is due to an incremental incidence of metabolic syndrome that is distinguished by dyslipidemia, glucose impairment, obesity, excessive oxidative stress and adipocytokine impairment...
August 2017: Biomedical Reports
https://www.readbyqxmd.com/read/28804516/the-role-of-sebelipase-alfa-in-the-treatment-of-lysosomal-acid-lipase-deficiency
#11
REVIEW
Angelika L Erwin
Lysosomal acid lipase deficiency (LALD) is a lysosomal storage disorder (LSD) characterized either by infantile onset with fulminant clinical course and very poor prognosis or childhood/adult-onset disease with an attenuated phenotype. The disorder is often misdiagnosed or remains undiagnosed in children and adults due to a rather unspecific clinical presentation with dyslipidemia and steatohepatitis. Until recently, no good treatment options were available for LALD. Despite supportive and symptomatic therapies, death occurred before 1 year of age in patients with infantile-onset disease and patients with childhood/adult-onset LALD suffered from significant complications, such as liver cirrhosis, requiring liver transplantation and early-onset cardiovascular disease...
July 2017: Therapeutic Advances in Gastroenterology
https://www.readbyqxmd.com/read/28804243/a-quantitative-systems-pharmacology-platform-to-investigate-the-impact-of-alirocumab-and-cholesterol-lowering-therapies-on-lipid-profiles-and-plaque-characteristics
#12
Jeffrey E Ming, Ruth E Abrams, Derek W Bartlett, Mengdi Tao, Tu Nguyen, Howard Surks, Katherine Kudrycki, Ananth Kadambi, Christina M Friedrich, Nassim Djebli, Britta Goebel, Alex Koszycki, Meera Varshnaya, Joseph Elassal, Poulabi Banerjee, William J Sasiela, Michael J Reed, Jeffrey S Barrett, Karim Azer
Reduction in low-density lipoprotein cholesterol (LDL-C) is associated with decreased risk for cardiovascular disease. Alirocumab, an antibody to proprotein convertase subtilisin/kexin type 9 (PCSK9), significantly reduces LDL-C. Here, we report development of a quantitative systems pharmacology (QSP) model integrating peripheral and liver cholesterol metabolism, as well as PCSK9 function, to examine the mechanisms of action of alirocumab and other lipid-lowering therapies, including statins. The model predicts changes in LDL-C and other lipids that are consistent with effects observed in clinical trials of single or combined treatments of alirocumab and other treatments...
2017: Gene Regulation and Systems Biology
https://www.readbyqxmd.com/read/28803419/specific-periodontopathic-bacterial-infection-affects-hypertension-in-male-cardiovascular-disease-patients
#13
Norio Aoyama, Jun-Ichi Suzuki, Hidetoshi Kumagai, Yuichi Ikeda, Hiroshi Akazawa, Issei Komuro, Masato Minabe, Yuichi Izumi, Mitsuaki Isobe
Hypertension (HT) is a systemic disorder that results in the decline of quality of life and death. While patients with periodontitis are at a high risk of HT, little causal information has been provided to date. To clarify the relationship, periodontopathic bacterial infection in cardiovascular patients with or without HT was evaluated. The subjects were patients with (n = 412) or without (n = 199) HT who attended Tokyo Medical and Dental University hospital. Blood examinations and periodontal measurements were performed...
August 12, 2017: Heart and Vessels
https://www.readbyqxmd.com/read/28803122/comparison-of-pharmacokinetics-and-safety-of-a-fixed-dose-combination-of-rosuvastatin-and-ezetimibe-versus-separate-tablets-in-healthy-subjects
#14
Kyoung Lok Min, Min Soo Park, Jina Jung, Min Jung Chang, Choon Ok Kim
PURPOSE: Rosuvastatin and ezetimibe are concomitantly used for dyslipidemia treatment. Compared with separate tablets, fixed-dose combination (FDC) tablets of rosuvastatin/ezetimibe could increase patient compliance. The aim of this study was to compare the pharmacokinetic (PK) profiles of an FDC tablet of rosuvastatin/ezetimibe and co-administration of rosuvastatin and ezetimibe as separate tablets in healthy Korean volunteers. METHODS: This trial was a randomized, open-label, single-dose, 2-way crossover study...
August 9, 2017: Clinical Therapeutics
https://www.readbyqxmd.com/read/28802699/relationship-between-limited-joint-mobility-of-hand-and-carotid-atherosclerosis-in-patients-with-type-2-diabetes
#15
Yusuke Mineoka, Michiyo Ishii, Yoshitaka Hashimoto, Muhei Tanaka, Naoto Nakamura, Yasukazu Katsumi, Motohide Isono, Michiaki Fukui
AIM: Limited joint mobility (LJM) of hand, which is one of a complication of diabetic hand, has a close association with diabetic microangiopathy. However, it remains to be elucidated about the relationships between LJM of hand and subclinical atherosclerosis in patients with type 2 diabetes. Therefore, we conducted a cross-sectional study to evaluate the relationships between LJM of hand and carotid intima-media thickness (IMT) and plaque score in patients with type 2 diabetes. METHODS: We evaluated the relationships between LJM of hand, and carotid IMT and plaque score, evaluated by carotid ultrasound examination, in 341 consecutive patients with type 2 diabetes...
July 20, 2017: Diabetes Research and Clinical Practice
https://www.readbyqxmd.com/read/28802120/discovery-of-pentacyclic-triterpene-3%C3%AE-ester-derivatives-as-a-new-class-of-cholesterol-ester-transfer-protein-inhibitors
#16
Dongyin Chen, Xin Huang, Hongwen Zhou, Hanqiong Luo, Pengfei Wang, Yongzhi Chang, Xinyi He, Suiying Ni, Qingqing Shen, Guoshen Cao, Hongbin Sun, Xiaoan Wen, Jun Liu
A series of pentacyclic triterpene 3β-ester derivatives were designed, synthesized and evaluated as a new class of cholesteryl ester transfer protein (CETP) inhibitors for the treatment of dyslipidemia. In vitro screening assay showed that 5 out of 30 compounds displayed moderate inhibiting human CETP activity with IC50s less than 10 μM. Among them, compound 20 (IC50 = 2.3 μM) had the most potent biological activity, and effectively ameliorated plasma lipid levels of human adipose tissue specific CETP transgenic (ap2-CETPTg) mice and guinea pigs...
August 4, 2017: European Journal of Medicinal Chemistry
https://www.readbyqxmd.com/read/28801239/salsalate-activates-skeletal-muscle-thermogenesis-and-protects-mice-from-high-fat-diet-induced-metabolic-dysfunction
#17
Li Nie, Xin-Lu Yuan, Ke-Tao Jiang, Yu-Hui Jiang, Jin Yuan, Lan Luo, Shi-Wei Cui, Cheng Sun
Salsalate plays beneficial roles for ameliorating hyperglycemia and dyslipidemia in type 2 diabetes patients, but the underlying mechanisms are still poorly understood. In this study, by administering salsalate to mice fed with high fat diet and examining how salsalate rectifies metabolic dysfunction in these obese mice, we found that salsalate stimulated body temperature and attenuated body weight gain without affecting food intake. Our results showed that salsalate application decreased lipid accumulation in liver and epididymal white adipose tissue (eWAT), inhibited hepatic gluconeogenesis and improved insulin signaling transduction in eWAT...
August 4, 2017: EBioMedicine
https://www.readbyqxmd.com/read/28800751/prevalence-awareness-treatment-and-control-of-dyslipidemia-in-older-persons-in-urban-and-rural-population-in-the-astana-region-kazakhstan
#18
Adil Supiyev, Talgat Nurgozhin, Zhaxybay Zhumadilov, Anne Peasey, Jaroslav A Hubacek, Martin Bobak
BACKGROUND: Despite high cardiovascular mortality in Central Asian republics of the former Soviet Union, there is limited information about major risk factors, including blood lipids. We investigated the prevalence of impaired concentrations of blood lipids, the awareness, treatment and control of hypercholesterolemia, and factors associated with these indicators in urban and rural populations in Kazakhstan. METHODS: We conducted a cross-sectional study of random urban and rural population samples (the state capital Astana and Akmol village)...
August 11, 2017: BMC Public Health
https://www.readbyqxmd.com/read/28800453/discovery-of-cycloalkyl-fused-n-thiazol-2-yl-benzamides-as-tissue-non-specific-glucokinase-activators-design-synthesis-and-biological-evaluation
#19
Zhengyu Wang, Xiaofan Shi, Huan Zhang, Liang Yu, Yanhua Cheng, Hefeng Zhang, Huibin Zhang, Jinpei Zhou, Jing Chen, Xu Shen, Wenhu Duan
Glucokinase (GK) activators are being developed for the treatment of type 2 diabetes mellitus (T2DM). However, existing GK activators have risks of hypoglycemia caused by over-activation of GK in islet cells and dyslipidemia caused by over-activation of intrahepatic GK. In the effort to mitigate risks of hypoglycemia and dyslipidemia while maintaining the promising efficacy of GK activator, we investigated a series of cycloalkyl-fused N-thiazol-2-yl-benzamides as tissue non-specific partial GK activators, which led to the identification of compound 72 that showed a good balance between in vitro potency and enzyme kinetic parameters, and protected β-cells from streptozotocin-induced apoptosis...
July 25, 2017: European Journal of Medicinal Chemistry
https://www.readbyqxmd.com/read/28799999/features-of-cardiovascular-disease-in-low-income-and-middle-income-countries-in-adults-and-children-living-with-hiv
#20
Andrew W McCrary, Chidozie U Nduka, Saverio Stranges, Gerald S Bloomfield
PURPOSE OF REVIEW: The current article addresses crucial issues in identifying risk of cardiovascular disease (CVD) in people living with HIV in low-income and middle-income countries (LMICs). These issues are in need of urgent attention to advance our knowledge and inform actions to mitigate CVD in this population. We address CVDs in adults living with HIV as well as the unique aspects pertaining to children living with HIV (CLHIV), a group sorely under-represented in this field. RECENT FINDINGS: CVDs affecting adults such as hypertension, dyslipidemia, coronary artery disease, and heart failure, in addition to myocardial dysfunction, vascular diseases, and autoimmune phenomena are also being reported in CLHIV...
August 10, 2017: Current Opinion in HIV and AIDS
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