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Metabolic diseases

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https://www.readbyqxmd.com/read/28231412/impact-of-family-history-of-metabolic-traits-on-severity-of-nash-related-cirrhosis-a-cross-sectional-study
#1
Ajeet Singh Bhadoria, Chandan Kumar Kedarisetty, Chhagan Bihari, Guresh Kumar, Ankur Jindal, Ankit Bhardwaj, Varsha Shasthry, Tanmay Vyas, Jaya Benjamin, Shvetank Sharma, Manoj Kumar Sharma, Shiv Kumar Sarin
BACKGROUND AND AIMS: Familial aggregation of metabolic traits with fatty liver disease is well documented. However, there is scarcity of data regarding such association with non-alcoholic steato-hepatitis (NASH) related cirrhosis. This study was aimed to explore the association of family history of metabolic traits with severity of cirrhosis. METHODS: In a cross-sectional study, all consecutive patients with NASH related cirrhosis presenting to our tertiary care centre were included...
February 23, 2017: Liver International: Official Journal of the International Association for the Study of the Liver
https://www.readbyqxmd.com/read/28231247/favipiravir-pharmacokinetics-in-ebola-infected-patients-of-the-jiki-trial-reveals-concentrations-lower-than-targeted
#2
Thi Huyen Tram Nguyen, Jérémie Guedj, Xavier Anglaret, Cédric Laouénan, Vincent Madelain, Anne-Marie Taburet, Sylvain Baize, Daouda Sissoko, Boris Pastorino, Anne Rodallec, Géraldine Piorkowski, Sara Carazo, Mamoudou N Conde, Jean-Luc Gala, Joseph Akoi Bore, Caroline Carbonnelle, Frédéric Jacquot, Hervé Raoul, Denis Malvy, Xavier de Lamballerie, France Mentré
BACKGROUND: In 2014-2015, we assessed favipiravir tolerance and efficacy in patients with Ebola virus (EBOV) disease (EVD) in Guinea (JIKI trial). Because the drug had never been used before for this indication and that high concentrations of the drugs were needed to achieve antiviral efficacy against EBOV, a pharmacokinetic model had been used to propose relevant dosing regimen. Here we report the favipiravir plasma concentrations that were achieved in participants in the JIKI trial and put them in perspective with the model-based targeted concentrations...
February 23, 2017: PLoS Neglected Tropical Diseases
https://www.readbyqxmd.com/read/28231179/how-can-diet-affect-the-accumulation-of-advanced-glycation-end-products-in-the-human-body
#3
REVIEW
Axel Guilbaud, Celine Niquet-Leridon, Eric Boulanger, Frederic J Tessier
The accumulation of advanced glycation end products (AGEs) is associated with the complications of diabetes, kidney disease, metabolic disorders and degenerative diseases. It is recognized that the pool of glycation products found in the human body comes not only from an endogenous formation, but also from a dietary exposure to exogenous AGEs. In recent years, the development of pharmacologically-active ingredients aimed at inhibiting endogenous glycation has not been successful. Since the accumulation of AGEs in the human body appears to be progressive throughout life, an early preventive action against glycation could be effective through dietary adjustments or supplementation with purified micronutrients...
December 6, 2016: Foods (Basel, Switzerland)
https://www.readbyqxmd.com/read/28231146/calcium-in-gluten-free-life-health-related-and-nutritional-implications
#4
REVIEW
Urszula Krupa-Kozak, Natalia Drabińska
Calcium deficiency and metabolic bone diseases are a frequent co-morbidity of coeliac disease (CD). Gluten-free diet (GFD) is the only effective treatment of CD. However, CD patients on the strict GFD consume less than the recommended amounts of calcium. In this review, the main etiological factors responsible for calcium deficiency in CD were presented. Additionally, the research on the application of calcium supplements in the gluten-free breadmaking was reviewed, and its effect on the technological and sensory properties of baked products was indicated...
July 15, 2016: Foods (Basel, Switzerland)
https://www.readbyqxmd.com/read/28231052/review-the-role-of-peroxisome-proliferator-activated-receptor-in-the-treatment-of-non-alcoholic-fatty-liver-disease
#5
Xin Sun, Yan Zhang, Meilin Xie
Non-alcoholic fatty liver disease (NAFLD) has been defined as a spectrum of histological abnormalities and is characterized by significant and excessive accumulation of triglycerides in the hepatocytes in patients without alcohol consumption or other diseases. Current studies are targeting new molecular mechanisms that underlie NAFLD and associated metabolic disorders. Many therapeutic targets have been found and used in clinical studies. Peroxisome proliferator-activated receptors (PPARs) are among the potential targets and have been demonstrated to exert a pivotal role in modulation of NAFLD...
March 1, 2017: Acta Pharmaceutica
https://www.readbyqxmd.com/read/28231019/pro-inflammatory-cytokines-impair-vitamin-d-induced-host-defense-in-cultured-airway-epithelial-cells
#6
Jasmijn A Schrumpf, Gimano D Amatngalim, Joris B Veldkamp, Renate M Verhoosel, Dennis K Ninaber, Soledad R Ordonez, Anne M van der Does, Henk P Haagsman, Pieter S Hiemstra
Vitamin D is a regulator of host defense against infections and induces expression of the antimicrobial peptide hCAP18/LL-37. Vitamin D deficiency is associated with chronic inflammatory lung diseases and respiratory infections. However, it is incompletely understood if and how (chronic) airway inflammation affects vitamin D metabolism and action. We hypothesized that long-term exposure of primary bronchial epithelial cells (PBEC) to pro-inflammatory cytokines alters their vitamin D metabolism, antibacterial activity and expression of hCAP18/LL-37...
February 23, 2017: American Journal of Respiratory Cell and Molecular Biology
https://www.readbyqxmd.com/read/28230981/high-potency-phenylquinoxalinone-cystic-fibrosis-transmembrane-conductance-regulator-cftr-activators
#7
Jung-Ho Son, Jie S Zhu, Puay-Wah Phuan, Onur Cil, Andrew P Teuthorn, Colton K Ku, Sujin Lee, Alan S Verkman, Mark J Kurth
We previously identified phenylquinoxalinone CFTRact-J027 (4) as a cystic fibrosis transmembrane conductance regulator (CFTR) activator with an EC50 of ~200 nM, and demonstrated its therapeutic efficacy in mouse models of constipation. Here, structure-activity studies were done on 36 synthesized phenylquinoxalinone analogs to identify compounds with improved potency and altered metabolic stability. Synthesis of the phenylquinoxalinone core was generally accomplished by condensation of 1,2-phenylenediamines with substituted phenyloxoacetates...
February 23, 2017: Journal of Medicinal Chemistry
https://www.readbyqxmd.com/read/28230890/effect-of-testosterone-replacement-therapy-on-vitamin-d-and-fgf-23-levels-in-congenital-hypogonadism
#8
Cem Haymana, Alper Sonmez, Aydogan Aydogdu, Serkan Tapan, Yalcin Basaran, Coskun Meric, Kamil Baskoy, Abdullah Taslipinar, Mahmut Ilker Yilmaz, Omer Azal
INTRODUCTION: Patients with hypogonadism are at increased risk of cardiac and metabolic diseases and osteoporosis. Vitamin D and Fibroblast growth factor-23 (FGF-23) play role in the regulation of bone mineral metabolism and endothelial functions. Low vitamin D levels are reported in hypogonadism, while there is no data about the effect of testosterone replacement therapy (TRT). We investigated the effect of TRT on vitamin D and FGF-23 levels along with endothelial functions and insulin resistance in hypogonadal patients...
February 23, 2017: Endokrynologia Polska
https://www.readbyqxmd.com/read/28230862/inactivation-of-lsd1-triggers-senescence-in-trophoblast-stem-cells-by-induction-of-sirt4
#9
Josefina Castex, Dominica Willmann, Toufike Kanouni, Laura Arrigoni, Yan Li, Marcel Friedrich, Michael Schleicher, Simon Wöhrle, Mark Pearson, Norbert Kraut, Michaël Méret, Thomas Manke, Eric Metzger, Roland Schüle, Thomas Günther
Coordination of energy metabolism is essential for homeostasis of stem cells, whereas an imbalance in energy homeostasis causes disease and accelerated aging. Here we show that deletion or enzymatic inactivation of lysine-specific demethylase 1 (Lsd1) triggers senescence in trophoblast stem cells (TSCs). Genome-wide transcriptional profiling of TSCs following Lsd1 inhibition shows gene set enrichment of aging and metabolic pathways. Consistently, global metabolomic and phenotypic analyses disclose an unbalanced redox status, decreased glutamine anaplerosis and mitochondrial function...
February 23, 2017: Cell Death & Disease
https://www.readbyqxmd.com/read/28230822/disordered-redox-metabolism-of-brain-cells-in-rats-exposed-to-low-doses-of-ionizing-radiation-or-uhf-electromagnetic-radiation
#10
A P Burlaka, M O Druzhyna, A V Vovk, S М Lukin
AIM: To investigate the changes of redox-state of mammalian brain cells as the critical factor of initiation and formation of radiation damage of biological structures in setting of continuous exposure to low doses of ionizing radiation or fractionated ultra high frequency electromagnetic radiation (UHF EMR) at non-thermal levels. MATERIALS AND METHODS: The influence of low-intensity ionizing radiation was studied on outbred female rats kept for 1.5 years in the Chernobyl accident zone...
December 2016: Experimental Oncology
https://www.readbyqxmd.com/read/28230738/clinical-implications-of-20-hydroxyeicosatetraenoic-acid-in-the-kidney-liver-lung-and-brain-an-emerging-therapeutic-target
#11
REVIEW
Osama H Elshenawy, Sherif M Shoieb, Anwar Mohamed, Ayman O S El-Kadi
Cytochrome P450-mediated metabolism of arachidonic acid (AA) is an important pathway for the formation of eicosanoids. The ω-hydroxylation of AA generates significant levels of 20-hydroxyeicosatetraenoic acid (20-HETE) in various tissues. In the current review, we discussed the role of 20-HETE in the kidney, liver, lung, and brain during physiological and pathophysiological states. Moreover, we discussed the role of 20-HETE in tumor formation, metabolic syndrome and diabetes. In the kidney, 20-HETE is involved in modulation of preglomerular vascular tone and tubular ion transport...
February 20, 2017: Pharmaceutics
https://www.readbyqxmd.com/read/28230703/omics-and-cachexia
#12
Brigitte Twelkmeyer, Nicolas Tardif, Olav Rooyackers
PURPOSE OF REVIEW: The purpose of this review is to recapture recent advances in cachexia-related diseases, mainly cancer cachexia, and treatment using genomic, transcriptomics, proteomic, and metabolomics-related techniques. RECENT FINDINGS: From recent studies in the cancer cachexia field it is clear that the tumor has a direct effect on distant organs via its secretome. The affected pathways on the other hand were largely known from earlier studies with changes in energy-related pathways (mainly lipid metabolism) and the protein degradation pathways...
February 21, 2017: Current Opinion in Clinical Nutrition and Metabolic Care
https://www.readbyqxmd.com/read/28230476/agonal-stress-vesicles-detected-on-ultrastructural-examination-in-pediatrics-potential-mimicker-of-metabolic-disease
#13
John Hicks, Eric Wartchow, Debra Keaney, Gary Mierau
No abstract text is available yet for this article.
January 2017: Ultrastructural Pathology
https://www.readbyqxmd.com/read/28230336/the-endothelial-border-to-health-mechanistic-evidence-of-the-hyperglycemic-culprit-of-inflammatory-disease-acceleration
#14
REVIEW
Nina Waerling Hansen, Anker Jon Hansen, Anette Sams
The endothelial cell (EC) layer constitutes a barrier that controls movements of fluid, solutes and cells between blood and tissue. Further, the endothelial layer regulates vascular tone and directs local humoral and cellular inflammatory processes. The strategic position makes it an important player for maintenance of health and for development of a number of diseases. Endothelial dysfunction is known to be an important component of type 2 diabetes, but is also assumed to be involved in many other diseases, for example, rheumatoid arthritis, inflammatory bowel disease, asthma, and cardiovascular diseases...
March 2017: IUBMB Life
https://www.readbyqxmd.com/read/28230173/a-novel-physiological-role-for-cardiac-myoglobin-in-lipid-metabolism
#15
Ulrike B Hendgen-Cotta, Sonja Esfeld, Cristina Coman, Robert Ahrends, Ludger Klein-Hitpass, Ulrich Flögel, Tienush Rassaf, Matthias Totzeck
Continuous contractile activity of the heart is essential and the required energy is mostly provided by fatty acid (FA) oxidation. Myocardial lipid accumulation can lead to pathological responses, however the underlying mechanisms remain elusive. The role of myoglobin in dioxygen binding in cardiomyocytes and oxidative skeletal muscle has widely been appreciated. Our recent work established myoglobin as a protector of cardiac function in hypoxia and disease states. We here unravel a novel role of cardiac myoglobin in governing FA metabolism to ensure the physiological energy production through β-oxidation, preventing myocardial lipid accumulation and preserving cardiac functions...
February 23, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28230171/impact-of-genetic-variation-on-human-camkk2-regulation-by-ca-2-calmodulin-and-multisite-phosphorylation
#16
Matthew T O'Brien, Jonathan S Oakhill, Naomi X Y Ling, Christopher G Langendorf, Ashfaqul Hoque, Toby A Dite, Anthony R Means, Bruce E Kemp, John W Scott
The Ca(2+)-calmodulin dependent protein kinase kinase-2 (CaMKK2) is a key regulator of neuronal function and whole-body energy metabolism. Elevated CaMKK2 activity is strongly associated with prostate and hepatic cancers, whereas reduced CaMKK2 activity has been linked to schizophrenia and bipolar disease in humans. Here we report the functional effects of nine rare-variant point mutations that were detected in large-scale human genetic studies and cancer tissues, all of which occur close to two regulatory phosphorylation sites and the catalytic site on human CaMKK2...
February 23, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28230078/unravelling-the-metabolic-impact-of-sbs-associated-microbial-dysbiosis-insights-from-the-piglet-short-bowel-syndrome-model
#17
Prue M Pereira-Fantini, Sean G Byars, James Pitt, Susan Lapthorne, Fiona Fouhy, Paul D Cotter, Julie E Bines
Liver disease is a major source of morbidity and mortality in children with short bowel syndrome (SBS). SBS-associated microbial dysbiosis has recently been implicated in the development of SBS-associated liver disease (SBS-ALD), however the pathological implications of this association have not been explored. In this study high-throughput sequencing of colonic content from the well-validated piglet SBS-ALD model was examined to determine alterations in microbial communities, and concurrent metabolic alterations identified in urine samples via targeted mass spectrometry approaches (GC-MS, LC-MS, FIA-MS) further uncovered impacts of microbial disturbance on metabolic outcomes in SBS-ALD...
February 23, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28229935/mice-deficient-in-l-12-15-lipoxygenase-show-increased-vulnerability-to-3-nitropropionic-acid-neurotoxicity
#18
Yan He, Rita C Akumuo, Yuan Yang, Sandra J Hewett
Considerable evidence supports a contributory role for leukocyte-type 12/15 Lipoxygenase (L-12/15 LO) in mediating hippocampal and cortical neuronal injury in models of Alzheimer's disease and stroke. Whether L-12/15 LO contributes to neuronal injury in a model of Huntington's disease (HD) has yet to be determined. HD is characterized by marked striatal neuronal loss, which can be mimicked in humans and animals by inhibition of mitochondrial complex II using 3-Nitropropionic acid (3-NP). Herein, we compared histological and behavioral outcomes between mice that were wild-type or null for L-12/15 LO following systemic injection of 3NP...
February 13, 2017: Neuroscience Letters
https://www.readbyqxmd.com/read/28229926/the-role-of-frailty-in-explaining-the-association-between-the-metabolic-syndrome-and-mortality-in-older-adults
#19
Emiel O Hoogendijk, Martijn Huisman, Adriana J van Ballegooijen
The association between the metabolic syndrome (MetS) and adverse outcomes in older adults may be explained by other health conditions. This study examined the role of frailty in explaining the association between MetS and mortality, independent of comorbidity. Data were used from 1247 men and women aged ≥65years of the Longitudinal Aging Study Amsterdam. MetS was assessed using the definition of the US National Cholesterol Education Program. Frailty was measured by the frailty phenotype. Mortality was monitored from 1995 until 2015...
February 14, 2017: Experimental Gerontology
https://www.readbyqxmd.com/read/28229907/expression-and-functional-evaluation-of-biopharmaceuticals-made-in-plant-chloroplasts
#20
REVIEW
Bei Zhang, Balamurugan Shanmugaraj, Henry Daniell
After approval of the first plant-made biopharmaceutical by FDA for human use, many protein drugs are now in clinical development. Within the last decade, significant advances have been made in expression of heterologous complex/large proteins in chloroplasts of edible plants using codon optimized human or viral genes. Furthermore, advances in quantification enable determination of in-planta drug dosage. Oral delivery of plastid-made biopharmaceuticals (PMB) is affordable because it eliminates prohibitively expensive fermentation, purification processes addressing major challenges of short shelf-life after cold storage...
February 21, 2017: Current Opinion in Chemical Biology
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