Metabolic Modulators in Heart Disease: Past, Present, and Future.

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Lopaschuk, Gary D

2017-07-01

Ischemic heart disease and heart failure are leading causes of mortality and morbidity worldwide. They continue to be major burden on health care systems throughout the world, despite major advances made over the past 40 years in developing new therapeutic approaches to treat these debilitating diseases. A potential therapeutic approach that has been underutilized in treating ischemic heart disease and heart failure is "metabolic modulation." Major alterations in myocardial energy substrate metabolism occur in ischemic heart disease and heart failure, and are associated with an energy deficit in the heart. A metabolic shift from mitochondrial oxidative metabolism to glycolysis, as well as an uncoupling between glycolysis and glucose oxidation, plays a crucial role in the development of cardiac inefficiency (oxygen consumed per work performed) and functional impairment in ischemic heart disease as well as in heart failure. This has led to the concept that optimizing energy substrate use with metabolic modulators can be a potentially promising approach to decrease the severity of ischemic heart disease and heart failure, primarily by improving cardiac efficiency. Two approaches for metabolic modulator therapy are to stimulate myocardial glucose oxidation and/or inhibit fatty acid oxidation. In this review, the past, present, and future of metabolic modulators as an approach to optimizing myocardial energy substrate metabolism and treating ischemic heart disease and heart failure are discussed. This includes a discussion of pharmacological interventions that target enzymes involved in fatty acid uptake, fatty acid oxidation, and glucose oxidation in the heart, as well as enzymes involved in ketone and branched chain amino acid catabolism in the heart. Copyright © 2017 Canadian Cardiovascular Society. Published by Elsevier Inc. All rights reserved.

Migraine, cerebrovascular disease and the metabolic syndrome

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Alexandra J Sinclair

2012-01-01

Full Text Available Evidence is emerging that migraine is not solely a headache disorder. Observations that ischemic stroke could occur in the setting of a migraine attack, and that migraine headaches could be precipitated by cerebral ischemia, initially highlighted a possibly association between migraine and cerebrovascular disease. More recently, large population-based studies that have demonstrated that migraineurs are at increased risk of stroke outside the setting of a migraine attack have prompted the concept that migraine and cerebrovascular disease are comorbid conditions. Explanations for this association are numerous and widely debated, particularly as the comorbid association does not appear to be confined to the cerebral circulation as cardiovascular and peripheral vascular disease also appear to be comorbid with migraine. A growing body of evidence has also suggested that migraineurs are more likely to be obese, hypertensive, hyperlipidemic and have impaired insulin sensitivity, all features of the metabolic syndrome. The comorbid association between migraine and cerebrovascular disease may consequently be explained by migraineurs having the metabolic syndrome and consequently being at increased risk of cerebrovascular disease. This review will summarise the salient evidence suggesting a comorbid association between migraine, cerebrovascular disease and the metabolic syndrome.

Tissue Renin-Angiotensin Systems: A Unifying Hypothesis of Metabolic Disease

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Jeppe eSkov

2014-02-01

Full Text Available The actions of angiotensin peptides are diverse and locally acting tissue renin-angiotensin systems (RAS are present in almost all tissues of the body. An activated RAS strongly correlates to metabolic disease (e.g. diabetes and its complications and blockers of RAS have been demonstrated to prevent diabetes in humans.Hyperglycemia, obesity, hypertension, and cortisol are well-known risk factors of metabolic disease and all stimulate tissue RAS whereas glucagon-like peptide-1, vitamin D, and aerobic exercise are inhibitors of tissue RAS and to some extent can prevent metabolic disease. Furthermore, an activated tissue RAS deteriorates the same risk factors creating a system with several positive feedback pathways. The primary effector hormone of the RAS, angiotensin II, stimulates reactive oxygen species, induces tissue damage, and can be associated to most diabetic complications. Based on these observations we hypothesize that an activated tissue RAS is the principle cause of metabolic syndrome and type 2 diabetes, and additionally is mediating the majority of the metabolic complications. The involvement of positive feedback pathways may create a self-reinforcing state and explain why metabolic disease initiate and progress. The hypothesis plausibly unify the major predictors of metabolic disease and places tissue RAS regulation in the center of metabolic control.

Bile Acid Signaling in Metabolic Disease and Drug Therapy

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Li, Tiangang

2014-01-01

Bile acids are the end products of cholesterol catabolism. Hepatic bile acid synthesis accounts for a major fraction of daily cholesterol turnover in humans. Biliary secretion of bile acids generates bile flow and facilitates hepatobiliary secretion of lipids, lipophilic metabolites, and xenobiotics. In the intestine, bile acids are essential for the absorption, transport, and metabolism of dietary fats and lipid-soluble vitamins. Extensive research in the last 2 decades has unveiled new functions of bile acids as signaling molecules and metabolic integrators. The bile acid–activated nuclear receptors farnesoid X receptor, pregnane X receptor, constitutive androstane receptor, vitamin D receptor, and G protein–coupled bile acid receptor play critical roles in the regulation of lipid, glucose, and energy metabolism, inflammation, and drug metabolism and detoxification. Bile acid synthesis exhibits a strong diurnal rhythm, which is entrained by fasting and refeeding as well as nutrient status and plays an important role for maintaining metabolic homeostasis. Recent research revealed an interaction of liver bile acids and gut microbiota in the regulation of liver metabolism. Circadian disturbance and altered gut microbiota contribute to the pathogenesis of liver diseases, inflammatory bowel diseases, nonalcoholic fatty liver disease, diabetes, and obesity. Bile acids and their derivatives are potential therapeutic agents for treating metabolic diseases of the liver. PMID:25073467

Low starting dosage of infliximab with possible escalating dosage in psoriatic arthritis gives the same treatment results as standard dosage of adalimumab or etanercept: results from the nationwide Icelandic ICEBIO registry

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Gudbjornsson B

2018-05-01

Full Text Available Bjorn Gudbjornsson,1,2 Arni Jon Geirsson,3,4 Niels Steen Krogh5 1Centre for Rheumatology Research, University Hospital, Reykjavik, Iceland; 2Faculty of Medicine, University of Iceland, Reykjavik, Iceland; 3Department of Rheumatology, University Hospital, Reykjavik, Iceland; 4Laeknasetrid - Medical Clinic, University of Iceland, Reykjavik, Iceland; 5Zitelab Aps, Copenhagen, Denmark Objective: To explore differences in response to a low dosage regimen of infliximab with an escalating dosage in comparison to a standard dosage of etanercept and adalimumab in patients with psoriatic arthritis (PsA. Methods: Biologically naïve PsA patients who were beginning anti-TNF-α therapy were selected from the ICEBIO registry. Demographics and clinical differences were compared in four treatment groups: infliximab <4 mg/kg; infliximab >4 mg/kg; etanercept or adalimumab at baseline and on follow-up (6 and 12 months, last visit. The Kruskal–Wallis rank sum test was used for comparison of the groups and the Wilcoxon test to compare the two infliximab dosage regimens. Results: One hundred and eighty-five patients (61% female were identified; 84 patients received infliximab, 66 etanercept, and 35 adalimumab. A total of 19% of the patients treated with infliximab escalated their dosage ≥4 mg/kg. No significant differences were observed at baseline in respect to visual analog scale (VAS pain, VAS fatigue, Health Assessment Questionnaire, C-reactive protein (CRP, numbers of swollen or tender joints, or Disease Activity Score (DAS 28-CRP values. A similar treatment response was observed in all four treatment groups on follow-up. Conclusion: In respect to treatment effects, a low dosage of infliximab with possible escalating dosage is acceptable for the majority of PsA patients who are in need of biological treatment. Keywords: psoriatic arthritis, outcome, biological treatment, routine care, clinical nationwide registry

Metaflammation, NLRP3 Inflammasome Obesity and Metabolic Disease

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Anna Meiliana

2011-12-01

Full Text Available BACKGROUND: Increasing prevalence of obesity gives rise to many problems associated with multiple morbidities, such as diabetes, hypertension, heart disease, sleep apnea and cancer. The mechanism of obesity is very complex, thus its link to various disease is poorly understood. This review highlights important concepts in our understanding of the pathogenesis of obesity and related complications. CONTENT: Many studies have tried to explore the exciting and puzzling links between metabolic homeostasis and inflammatory responses. A form of subclinical, low-grade systemic inflammation is known to be associated with both obesity and chronic disease. This, later called as "metaflammation", refers to metabolically triggered inflammation. The nutrient-sensing pathway and the immune response coordination are facilitated by these molecular sites in order to maintain homeostasis under diverse metabolic and immune conditions. Recent studies have found that the NLRP3 inflammasome during metabolic stress forms a tie linking TXNIP, oxidative stress, and IL-1β production. This provides new opportunities for research and therapy for the disease often described as the next global pandemic: type 2 diabetes mellitus (T2DM. SUMMARY: The crucial role of metaflammation in many complications of obesity shown by the unexpected overlap between inflammatory and metabolic sensors and their downstream tissue responses. Then great interest arose to explore the pathways that integrate nutrient and pathogen sensing, give more understanding in the mechanisms of insulin resistance type 2 diabetes, and other chronic metabolic pathologies. A family of intracellular sensors called NLR family is a critical component of the innate immune system. They can form multiprotein complexes, called inflammasome which is capable of responding to a wide range of stimuli including both microbial and self molecules by activating the cysteine protease caspase-1, leading to processing and

Sphingolipid metabolism diseases.

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Kolter, Thomas; Sandhoff, Konrad

2006-12-01

Human diseases caused by alterations in the metabolism of sphingolipids or glycosphingolipids are mainly disorders of the degradation of these compounds. The sphingolipidoses are a group of monogenic inherited diseases caused by defects in the system of lysosomal sphingolipid degradation, with subsequent accumulation of non-degradable storage material in one or more organs. Most sphingolipidoses are associated with high mortality. Both, the ratio of substrate influx into the lysosomes and the reduced degradative capacity can be addressed by therapeutic approaches. In addition to symptomatic treatments, the current strategies for restoration of the reduced substrate degradation within the lysosome are enzyme replacement therapy (ERT), cell-mediated therapy (CMT) including bone marrow transplantation (BMT) and cell-mediated "cross correction", gene therapy, and enzyme-enhancement therapy with chemical chaperones. The reduction of substrate influx into the lysosomes can be achieved by substrate reduction therapy. Patients suffering from the attenuated form (type 1) of Gaucher disease and from Fabry disease have been successfully treated with ERT.

Urinary Metabolic Phenotyping Reveals Differences in the Metabolic Status of Healthy and Inflammatory Bowel Disease (IBD Children in Relation to Growth and Disease Activity

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Francois-Pierre Martin

2016-08-01

Full Text Available Background: Growth failure and delayed puberty are well known features of children and adolescents with inflammatory bowel disease (IBD, in addition to the chronic course of the disease. Urinary metabonomics was applied in order to better understand metabolic changes between healthy and IBD children. Methods: 21 Pediatric patients with IBD (mean age 14.8 years, 8 males were enrolled from the Pediatric Gastroenterology Outpatient Clinic over two years. Clinical and biological data were collected at baseline, 6, and 12 months. 27 healthy children (mean age 12.9 years, 16 males were assessed at baseline. Urine samples were collected at each visit and subjected to 1H Nuclear Magnetic Resonance (NMR spectroscopy. Results: Using 1H NMR metabonomics, we determined that urine metabolic profiles of IBD children differ significantly from healthy controls. Metabolic differences include central energy metabolism, amino acid, and gut microbial metabolic pathways. The analysis described that combined urinary urea and phenylacetylglutamine—two readouts of nitrogen metabolism—may be relevant to monitor metabolic status in the course of disease. Conclusion: Non-invasive sampling of urine followed by metabonomic profiling can elucidate and monitor the metabolic status of children in relation to disease status. Further developments of omic-approaches in pediatric research might deliver novel nutritional and metabolic hypotheses.

Metabolic Diseases of Muscle

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... here and still get the great care and treatment I received in Michigan.” MDA Is Here to Help You T he Muscular Dystrophy Association offers a vast array of services to help you and your family deal with metabolic diseases of muscle. The staff at your local MDA office is ...

Abdominal ultrasonography in inheredited diseases of carbohydrate metabolism

International Nuclear Information System (INIS)

Pozzato, Carlo; Curti, Alessandra; Cornalba, Gianpaolo; Radaelli, Giovanni; Fiori, Laura; Rossi, Samantha; Riva, Enrica

2005-01-01

Purpose: To determine the usefulness of abdominal sonography in inherited diseases of carbohydrate metabolism. Materials and methods: Thirty patients (age range, 4 months to 27 years) with glycogen storage diseases, galactosemia, disorders of fructose metabolism were studied with sonography. Echogenicity of the liver, sonographic dimensions of liver, kidneys and spleen were evaluated. Plasma blood parameters (ALT, AST, total cholesterol, triglycerides) were determined. Results: Liver was enlarged in 21/22 patients (95.4%) with glycogen storage diseases, in both subjects with disorders of fructose metabolism, and in 2/6 patients (33.3%) with galactosemia. Hepatic echogenicity was increased in 20/22 patients (90.9%) with glycogen storage diseases, and in the subject with hereditary fructose intolerance. Patients with galactosemia did not show increased liver echogenicity. Both kidney were enlarged in 8/17 patients (47.0%) with glycogen storage disease type I. Subjects with increased hepatic echogenicity exhibited higher plasma concentrations of any blood parameter than the others with normal echogenicity (p [it

Biochemical markers of psoriasis as a metabolic disease

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Agnieszka Gerkowicz

2012-07-01

Full Text Available Psoriasis is a chronic immune mediated inflammatory skin disease with a population prevalence of 2–3%. In recent years, psoriasis has been recognized as a systemic disease associated with metabolic syndrome or its components such as: obesity, insulin resistance, hypertension and atherogenic dyslipidemia. Many bioactive substances have appeared to be related to metabolic syndrome. Based on current literature, we here discuss the possible role of adiponectin, leptin, ghrelin, resistin, inflammatory cytokines, plasminogen activator inhibitor 1, uric acid, C-reactive protein and lipid abnormalities in psoriasis and in metabolic syndrome.

Exercise-induced myokines in health and metabolic diseases

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Byunghun So

2014-12-01

Full Text Available Skeletal muscle has been emerging as a research field since the past 2 decades. Contraction of a muscle, which acts as a secretory organ, stimulates production, secretion, and expression of cytokines or other muscle fiber-derived peptides, i.e., myokines. Exercise-induced myokines influence crosstalk between different organs in an autocrine, endocrine, or paracrine fashion. Myokines are recently recognized as potential candidates for treating metabolic diseases through their ability to stimulate AMP-activated protein kinase signaling, increase glucose uptake, and improve lipolysis. Myokines may have positive effects on metabolic disorders, type 2 diabetes, or obesity. Numerous studies on myokines suggested that myokines offer a potential treatment option for preventing metabolic diseases. This review summarizes the current understanding of the positive effects of exercise-induced myokines, such as interleukin-15, brain-derived neurotrophic factor, leukemia inhibitory factor, irisin, fibroblast growth factor 21, and secreted protein acidic and rich in cysteine, on metabolic diseases.

[Metabolic bone disease osteomalacia].

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Reuss-Borst, M A

2014-05-01

Osteomalacia is a rare disorder of bone metabolism leading to reduced bone mineralization. Underlying vitamin D deficiency and a disturbed phosphate metabolism (so-called hypophosphatemic osteomalacia) can cause the disease. Leading symptoms are dull localized or generalized bone pain, muscle weakness and cramps as well as increased incidence of falls. Rheumatic diseases, such as polymyalgia rheumatica, rheumatoid arthritis, myositis and fibromyalgia must be considered in the differential diagnosis. Alkaline phosphatase (AP) is typically elevated in osteomalacia while serum phosphate and/or 25-OH vitamin D3 levels are reduced. The diagnosis of osteomalacia can be confirmed by an iliac crest bone biopsy. Histological correlate is reduced or deficient mineralization of the newly synthesized extracellular matrix. Treatment strategies comprise supplementation of vitamin D and calcium and for patients with intestinal malabsorption syndromes vitamin D and calcium are also given parenterally. In renal phosphate wasting syndromes substitution of phosphate is the treatment of choice, except for tumor-induced osteomalacia when removal of the tumor leads to a cure in most cases.

Metabolism and elimination of methyl, iso- and n-butyl paraben in human urine after single oral dosage.

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Moos, Rebecca K; Angerer, Jürgen; Dierkes, Georg; Brüning, Thomas; Koch, Holger M

2016-11-01

Parabens are used as preservatives in personal care and consumer products, food and pharmaceuticals. Their use is controversial because of possible endocrine disrupting properties. In this study, we investigated metabolism and urinary excretion of methyl paraben (MeP), iso-butyl paraben (iso-BuP) and n-butyl paraben (n-BuP) after oral dosage of deuterium-labeled analogs (10 mg). Each volunteer received one dosage per investigated paraben separately and at least 2 weeks apart. Consecutive urine samples were collected over 48 h. In addition to the parent parabens (free and conjugated) which are already used as biomarkers of internal exposure and the known but non-specific metabolites, p-hydroxybenzoic acid (PHBA) and p-hydroxyhippuric acid (PHHA), we identified new, oxidized metabolites with hydroxy groups on the alkyl side chain (3OH-n-BuP and 2OH-iso-BuP) and species with oxidative modifications on the aromatic ring. MeP represented 17.4 % of the dose excreted in urine, while iso-BuP represented only 6.8 % and n-BuP 5.6 %. Additionally, for iso-BuP, about 16 % was excreted as 2OH-iso-BuP and for n-BuP about 6 % as 3OH-n-BuP. Less than 1 % was excreted as ring-hydroxylated metabolites. In all cases, PHHA was identified as the major but non-specific metabolite (57.2-63.8 %). PHBA represented 3.0-7.2 %. For all parabens, the majority of the oral dose captured by the above metabolites was excreted in the first 24 h (80.5-85.3 %). Complementary to the parent parabens excreted in urine, alkyl-chain-oxidized metabolites of the butyl parabens are introduced as valuable and contamination-free biomarkers of exposure.

The Metabolic Role of Gut Microbiota in the Development of Nonalcoholic Fatty Liver Disease and Cardiovascular Disease

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Marco Sanduzzi Zamparelli

2016-07-01

Full Text Available The prevalence of metabolic disorders, such as type 2 diabetes (T2D, obesity, and non-alcoholic fatty liver disease (NAFLD, which are common risk factors for cardiovascular disease (CVD, has dramatically increased worldwide over the last decades. Although dietary habit is the main etiologic factor, there is an imperfect correlation between dietary habits and the development of metabolic disease. Recently, research has focused on the role of the microbiome in the development of these disorders. Indeed, gut microbiota is implicated in many metabolic functions and an altered gut microbiota is reported in metabolic disorders. Here we provide evidence linking gut microbiota and metabolic diseases, focusing on the pathogenetic mechanisms underlying this association.

Minimum effective dosages of anti-TNF in rheumatoid arthritis: a cross-sectional study.

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de la Torre, Inmaculada; Valor, Lara; Nieto, Juan Carlos; Montoro, María; Carreño, Luis

2014-01-01

To evaluate the modified dosages of anti-TNF in controlling disease activity in rheumatoid arthritis (RA) measured by DAS28-ESR. Cross-sectional study: RA patients treated with etanercept (ETN), adalimumab (ADA) or infliximab (IFX), at standard or modified doses. dosage, concomitant disease modifying drugs (DMARDs), DAS28-ESR. 195 RA patients included (79% women, mean age 58.1 years): ETN=81, ADA=56, IFX=58. Mean disease duration and time to first biological treatment was higher in IFX group (P=.01). Patients distribution by dosage: standard: ETN (72.8%), ADA (69.6%), IFX (27.6%); escalated: IFX (69%), ADA (5.4%), ETN (0%); reduced: ETN (27.1%), ADA (25%), IFX (3.4%). Concomitant DMARDs use was lower in ETN (58.2%) than ADA (66.07%) and IFX (79.31%). Higher proportion of responders (DAS28 ≤3.2) in ADA (65.3%) and ETN (61.7%) than IFX (48.3%). RA clinical control can be preserved with modified anti-TNF dosages. Controlled prospective studies should be performed to define when therapy can be tailored and for which patients. Copyright © 2013 Elsevier España, S.L. All rights reserved.

Sortilin and Its Multiple Roles in Cardiovascular and Metabolic Diseases

DEFF Research Database (Denmark)

Goettsch, Claudia; Kjølby, Mads Fuglsang; Aikawa, Elena

2018-01-01

Cardiovascular disease is a leading cause of morbidity and mortality in the Western world. Studies of sortilin's influence on cardiovascular and metabolic diseases goes far beyond the genome-wide association studies that have revealed an association between cardiovascular diseases and the 1p13...... locus that encodes sortilin. Emerging evidence suggests a significant role of sortilin in the pathogenesis of vascular and metabolic diseases; this includes type II diabetes mellitus via regulation of insulin resistance, atherosclerosis through arterial wall inflammation and calcification...... of sortilin's contributions to cardiovascular and metabolic diseases but focuses particularly on atherosclerosis. We summarize recent clinical findings that suggest that sortilin may be a cardiovascular risk biomarker and also discuss sortilin as a potential drug target....

BioM2MetDisease: a manually curated database for associations between microRNAs, metabolites, small molecules and metabolic diseases.

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Xu, Yanjun; Yang, Haixiu; Wu, Tan; Dong, Qun; Sun, Zeguo; Shang, Desi; Li, Feng; Xu, Yingqi; Su, Fei; Liu, Siyao; Zhang, Yunpeng; Li, Xia

2017-01-01

BioM2MetDisease is a manually curated database that aims to provide a comprehensive and experimentally supported resource of associations between metabolic diseases and various biomolecules. Recently, metabolic diseases such as diabetes have become one of the leading threats to people’s health. Metabolic disease associated with alterations of multiple types of biomolecules such as miRNAs and metabolites. An integrated and high-quality data source that collection of metabolic disease associated biomolecules is essential for exploring the underlying molecular mechanisms and discovering novel therapeutics. Here, we developed the BioM2MetDisease database, which currently documents 2681 entries of relationships between 1147 biomolecules (miRNAs, metabolites and small molecules/drugs) and 78 metabolic diseases across 14 species. Each entry includes biomolecule category, species, biomolecule name, disease name, dysregulation pattern, experimental technique, a brief description of metabolic disease-biomolecule relationships, the reference, additional annotation information etc. BioM2MetDisease provides a user-friendly interface to explore and retrieve all data conveniently. A submission page was also offered for researchers to submit new associations between biomolecules and metabolic diseases. BioM2MetDisease provides a comprehensive resource for studying biology molecules act in metabolic diseases, and it is helpful for understanding the molecular mechanisms and developing novel therapeutics for metabolic diseases. http://www.bio-bigdata.com/BioM2MetDisease/. © The Author(s) 2017. Published by Oxford University Press.

Cardiorenal metabolic syndrome in the African diaspora: rationale for including chronic kidney disease in the metabolic syndrome definition.

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Lea, Janice P; Greene, Eddie L; Nicholas, Susanne B; Agodoa, Lawrence; Norris, Keith C

2009-01-01

Chronic kidney disease (CKD) is more likely to progress to end-stage renal disease (ESRD) in African Americans while the reasons for this are unclear. The metabolic syndrome is a risk factor for the development of diabetes, cardiovascular disease, and has been recently linked to incident CKD. Historically, fewer African Americans meet criteria for the definition of metabolic syndrome, despite having higher rates of cardiovascular mortality than Caucasians. The presence of microalbuminuria portends increased cardiovascular risks and has been shown to cluster with the metabolic syndrome. We recently reported that proteinuria is a predictor of CKD progression in African American hypertensives with metabolic syndrome. In this review we explore the potential value of including CKD markers--microalbuminuria/proteinuria or low glomerular filtration rate (GFR)-in refining the cluster of factors defined as metabolic syndrome, ie, "cardiorenal metabolic syndrome."

Targeting Adipose Tissue Lipid Metabolism to Improve Glucose Metabolism in Cardiometabolic Disease

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Johan W.E. Jocken

2014-10-01

Full Text Available With Type 2 diabetes mellitus and cardiovascular disease prevalence on the rise, there is a growing need for improved strategies to prevent or treat obesity and insulin resistance, both of which are major risk factors for these chronic diseases. Impairments in adipose tissue lipid metabolism seem to play a critical role in these disorders. In the classical picture of intracellular lipid breakdown, cytosolic lipolysis was proposed as the sole mechanism for triacylglycerol hydrolysis in adipocytes. Recent evidence suggests involvement of several hormones, membrane receptors, and intracellular signalling cascades, which has added complexity to the regulation of cytosolic lipolysis. Interestingly, a specific form of autophagy, called lipophagy, has been implicated as alternative lipolytic pathway. Defective regulation of cytosolic lipolysis and lipophagy might have substantial effects on lipid metabolism, thereby contributing to adipose tissue dysfunction, insulin resistance, and related cardiometabolic (cMet diseases. This review will discuss recent advances in our understanding of classical lipolysis and lipophagy in adipocyte lipid metabolism under normal and pathological conditions. Furthermore, the question of whether modulation of adipocyte lipolysis and lipophagy might be a potential therapeutic target to combat cMet disorders will be addressed.

Semi-quantitative interpretation of the bone scan in metabolic bone disease

Energy Technology Data Exchange (ETDEWEB)

Fogelman, I; Turner, J G; Hay, I D; Boyle, I T [Royal Infirmary, Glasgow (UK). Dept. of Nuclear Medicine; Citrin, D L [Wisconsin Univ., Madison (USA). Dept. of Human Oncology; Bessent, G R

1979-01-01

Certain easily recognisable features are commonly seen in the bone scans of patients with metabolic bone disorders. Seven such features have been numerically graded by three independent observers in the scans of 100 patients with metabolic bone disease and of 50 control subjects. The total score for each patient is defined as the metabolic index. The mean metabolic index for each group of patients with metabolic bone disease is significantly greater than that for the control group (P < 0.001). (orig.).

metabolicMine: an integrated genomics, genetics and proteomics data warehouse for common metabolic disease research.

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Lyne, Mike; Smith, Richard N; Lyne, Rachel; Aleksic, Jelena; Hu, Fengyuan; Kalderimis, Alex; Stepan, Radek; Micklem, Gos

2013-01-01

Common metabolic and endocrine diseases such as diabetes affect millions of people worldwide and have a major health impact, frequently leading to complications and mortality. In a search for better prevention and treatment, there is ongoing research into the underlying molecular and genetic bases of these complex human diseases, as well as into the links with risk factors such as obesity. Although an increasing number of relevant genomic and proteomic data sets have become available, the quantity and diversity of the data make their efficient exploitation challenging. Here, we present metabolicMine, a data warehouse with a specific focus on the genomics, genetics and proteomics of common metabolic diseases. Developed in collaboration with leading UK metabolic disease groups, metabolicMine integrates data sets from a range of experiments and model organisms alongside tools for exploring them. The current version brings together information covering genes, proteins, orthologues, interactions, gene expression, pathways, ontologies, diseases, genome-wide association studies and single nucleotide polymorphisms. Although the emphasis is on human data, key data sets from mouse and rat are included. These are complemented by interoperation with the RatMine rat genomics database, with a corresponding mouse version under development by the Mouse Genome Informatics (MGI) group. The web interface contains a number of features including keyword search, a library of Search Forms, the QueryBuilder and list analysis tools. This provides researchers with many different ways to analyse, view and flexibly export data. Programming interfaces and automatic code generation in several languages are supported, and many of the features of the web interface are available through web services. The combination of diverse data sets integrated with analysis tools and a powerful query system makes metabolicMine a valuable research resource. The web interface makes it accessible to first

Interrelationship of canonical and non-canonical Wnt signalling pathways in chronic metabolic diseases.

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Ackers, Ian; Malgor, Ramiro

2018-01-01

Chronic diseases account for approximately 45% of all deaths in developed countries and are particularly prevalent in countries with the most sophisticated and robust public health systems. Chronic metabolic diseases, specifically lifestyle-related diseases pertaining to diet and exercise, continue to be difficult to treat clinically. The most prevalent of these chronic metabolic diseases include obesity, diabetes, non-alcoholic fatty liver disease, chronic kidney disease and cardiovascular disease and will be the focus of this review. Wnt proteins are highly conserved glycoproteins best known for their role in development and homeostasis of tissues. Given the importance of Wnt signalling in homeostasis, aberrant Wnt signalling likely regulates metabolic processes and may contribute to the development of chronic metabolic diseases. Expression of Wnt proteins and dysfunctional Wnt signalling has been reported in multiple chronic diseases. It is interesting to speculate about an interrelationship between the Wnt signalling pathways as a potential pathological mechanism in chronic metabolic diseases. The aim of this review is to summarize reported findings on the contrasting roles of Wnt signalling in lifestyle-related chronic metabolic diseases; specifically, the contribution of Wnt signalling to lipid accumulation, fibrosis and chronic low-grade inflammation.

INFORMATION SYSTEM FOR REGISTRY OF PATIENTS WITH METABOLIC DISEASES

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N. H. Horovenko

2015-05-01

Full Text Available This article describes the problems encountered in the management of medical records of patients with metabolic diseases, and also provides a general solution to these problems through the introduction of a software product. Objective was to reduce the burden on the healthcare registrars and medical genetics center, improving the speed and quality of patient care. In the software implementation the main features of the complex design problems are described: the programming language Java, IDE NetBeans, MySQL database server and web application to work with database server phpMyAdmin and put forward requirements. Also, medical receptionist is able to keep track of patients to form an extract, view statistics. During development were numerous consultations with experienced doctors, medical registrars. With the convenient architecture in the future will be easy to add custom modules in the program. Development of the program management of electronic medical records of patients the center of metabolic diseases is essential, because today in Ukraine all the software that can keep track of patients who did not drawn enough attention to patients with metabolic diseases. Currently the software is installed in the center of metabolic diseases NCSH “OKHMATDYT.”

Inflammation meets metabolic disease: Gut feeling mediated by GLP-1

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Tamara eZietek

2016-04-01

Full Text Available Chronic diseases such as obesity and diabetes, cardiovascular and inflammatory bowel diseases (IBD share common features in their pathology. Metabolic disorders exhibit strong inflammatory underpinnings and vice versa, inflammation is associated with metabolic alterations. Next to cytokines and cellular stress pathways like the unfolded protein response (UPR, alterations in the enteroendocrine system are intersections of various pathologies. Enteroendocrine cells (EEC have been studied extensively for their ability to regulate gastrointestinal motility, secretion, and insulin release by release of peptide hormones. In particular the L cell-derived incretin hormone glucagon-like peptide 1 (GLP-1 has gained enormous attention due to its insulinotropic action and relevance in the treatment of type 2 diabetes (T2D. Yet, accumulating data indicates a critical role for EEC and in particular for GLP-1 in metabolic adaptation and in orchestrating immune responses beyond blood glucose control. EEC sense the lamina propria and luminal environment including the microbiota via receptors and transporters. Subsequently mediating signals by secreting hormones and cytokines, EEC can be considered as integrators of metabolic and inflammatory signaling.This review focuses on L cell and GLP-1 functions in the context of metabolic and inflammatory diseases. The effects of incretin-based therapies on metabolism and immune system are discussed and the interrelation and common features of metabolic and immune-mediated disorders are highlighted. Moreover, it presents data on the impact of inflammation, in particular of IBD on EEC and discusses the potential role of the microbiota as link between nutrients, metabolism, immunity and disease.

A clinical perspective of obesity, metabolic syndrome and cardiovascular disease

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Thang S Han

2016-02-01

Full Text Available The metabolic syndrome is a condition characterized by a special constellation of reversible major risk factors for cardiovascular disease and type 2 diabetes. The main, diagnostic, components are reduced HDL-cholesterol, raised triglycerides, blood pressure and fasting plasma glucose, all of which are related to weight gain, specifically intra-abdominal/ectopic fat accumulation and a large waist circumference. Using internationally adopted arbitrary cut-off values for waist circumference, having metabolic syndrome doubles the risk of cardiovascular disease, but offers an effective treatment approach through weight management. Metabolic syndrome now affects 30–40% of people by age 65, driven mainly by adult weight gain, and by a genetic or epigenetic predisposition to intra-abdominal/ectopic fat accumulation related to poor intra-uterine growth. Metabolic syndrome is also promoted by a lack of subcutaneous adipose tissue, low skeletal muscle mass and anti-retroviral drugs. Reducing weight by 5–10%, by diet and exercise, with or without, anti-obesity drugs, substantially lowers all metabolic syndrome components, and risk of type 2 diabetes and cardiovascular disease. Other cardiovascular disease risk factors such as smoking should be corrected as a priority. Anti-diabetic agents which improve insulin resistance and reduce blood pressure, lipids and weight should be preferred for diabetic patients with metabolic syndrome. Bariatric surgery offers an alternative treatment for those with BMI ≥ 40 or 35–40 kg/m 2 with other significant co-morbidity. The prevalence of the metabolic syndrome and cardiovascular disease is expected to rise along with the global obesity epidemic: greater emphasis should be given to effective early weight-management to reduce risk in pre-symptomatic individuals with large waists.

Apolipoprotein M in lipid metabolism and cardiometabolic diseases

DEFF Research Database (Denmark)

Borup, Anna; Christensen, Pernille Meyer; Nielsen, Lars B.

2015-01-01

: The apoM/S1P axis and its implications in atherosclerosis and lipid metabolism have been thoroughly studied. Owing to the discovery of the apoM/S1P axis, the scope of apoM research has broadened. ApoM and S1P have been implicated in lipid metabolism, that is by modulating HDL particles. Also......PURPOSE: This review will address recent findings on apolipoprotein M (apoM) and its ligand sphingosine-1-phosphate (S1P) in lipid metabolism and inflammatory diseases. RECENT FINDINGS: ApoM's likely role(s) in health and disease has become more diverse after the discovery that apoM functions...... as a chaperone for S1P. Hence, apoM has recently been implicated in lipid metabolism, diabetes and rheumatoid arthritis through in-vivo, in-vitro and genetic association studies. It remains to be established to which degree such associations with apoM can be attributed to its ability to bind S1P. SUMMARY...

Neural expression and post-transcriptional dosage compensation of the steroid metabolic enzyme 17β-HSD type 4

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Wise Petra M

2010-04-01

Full Text Available Abstract Background Steroids affect many tissues, including the brain. In the zebra finch, the estrogenic steroid estradiol (E2 is especially effective at promoting growth of the neural circuit specialized for song. In this species, only the males sing and they have a much larger and more interconnected song circuit than females. Thus, it was surprising that the gene for 17β-hydroxysteroid dehydrogenase type 4 (HSD17B4, an enzyme that converts E2 to a less potent estrogen, had been mapped to the Z sex chromosome. As a consequence, it was likely that HSD17B4 was differentially expressed in males (ZZ and females (ZW because dosage compensation of Z chromosome genes is incomplete in birds. If a higher abundance of HSD17B4 mRNA in males than females was translated into functional enzyme in the brain, then contrary to expectation, males could produce less E2 in their brains than females. Results Here, we used molecular and biochemical techniques to confirm the HSD17B4 Z chromosome location in the zebra finch and to determine that HSD17B4 mRNA and activity were detectable in the early developing and adult brain. As expected, HSD17B4 mRNA expression levels were higher in males compared to females. This provides further evidence of the incomplete Z chromosome inactivation mechanisms in birds. We detected HSD17B4 mRNA in regions that suggested a role for this enzyme in the early organization and adult function of song nuclei. We did not, however, detect significant sex differences in HSD17B4 activity levels in the adult brain. Conclusions Our results demonstrate that the HSD17B4 gene is expressed and active in the zebra finch brain as an E2 metabolizing enzyme, but that dosage compensation of this Z-linked gene may occur via post-transcriptional mechanisms.

Marine Omega-3 Fatty Acids, Complications of Pregnancy and Maternal Risk Factors for Offspring Cardio-Metabolic Disease

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Melinda Phang

2018-04-01

Full Text Available Marine omega-3 polyunsaturated fatty acids (n-3 PUFA are important nutrients during periods of rapid growth and development in utero and infancy. Maternal health and risk factors play a crucial role in birth outcomes and subsequently offspring cardio-metabolic health. Evidence from observational studies and randomized trials have suggested a potential association of maternal intake of marine n-3 PUFAs during pregnancy with pregnancy and birth outcomes. However, there is inconsistency in the literature on whether marine n-3 PUFA supplementation during pregnancy can prevent maternal complications of pregnancy. This narrative literature review summarizes recent evidence on observational and clinical trials of marine n-3 PUFA intake on maternal risk factors and effects on offspring cardio-metabolic health. The current evidence generally does not support a role of maternal n-3 PUFA supplementation in altering the incidence of gestational diabetes, pregnancy-induced hypertension, or pre-eclampsia. It may be that benefits from marine n-3 PUFA supplementation are more pronounced in high-risk populations, such as women with a history of complications of pregnancy, or women with low marine n-3 PUFA intake. Discrepancies between studies may be related to differences in study design, dosage, fatty acid interplay, and length of treatment. Further prospective double-blind studies are needed to clarify the impact of long-chain marine n-3 PUFAs on risk factors for cardio-metabolic disease in the offspring.

Metabolic syndrome in patients with ischemic heart disease

International Nuclear Information System (INIS)

Yasmin, S.; Naveed, T.; Shakoor, T.

2008-01-01

To determine the frequency of metabolic syndrome in patients with Ischemic Heart Disease (IHD). Cross-sectional, descriptive study. A total of 100 subjects with ischemic heart disease, fulfilling the inclusion criteria, were enrolled in the study. Demographic data (age and gender) and the 5 component conditions of the metabolic syndrome were noted. Subjects were physically assessed for the abdominal obesity, based on waist circumference. Fasting blood samples for glucose and lipid profile in first 24 hours after acute coronary insult were drawn and tested in central laboratory. Variables were processed for descriptive statistics. In this study population, 68% were male and 32% were female with mean age of 52 +-13.6 years in men and 56 +- 12.5 years in women. Frequency of metabolic syndrome was 32% in men and 28% in women. It increased with age. The highest rate of metabolic syndrome was in men diagnosed as STEMI (odds ratio: 3.39, 95% CI=1.36-8.41). Frequency of metabolic syndrome was high among the patients with IHD. It supports the potential for preventive efforts in persons with high-risk of IHD. (author)

Celiac disease: A missed cause of metabolic bone disease

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Ashu Rastogi

2012-01-01

Full Text Available Introduction: Celiac disease (CD is a highly prevalent autoimmune disease. The symptoms of CD are varied and atypical, with many patients having no gastrointestinal symptoms. Metabolic bone disease (MBD is a less recognized manifestation of CD associated with spectrum of musculoskeletal signs and symptoms, viz. bone pains, proximal muscle weakness, osteopenia, osteoporosis, and fracture. We here report five patients who presented with severe MBD as the only manifestation of CD. Materials and Methods: Records of 825 patients of CD diagnosed during 2002-2010 were retrospectively analyzed for clinical features, risk factors, signs, biochemical, and radiological parameters. Results: We were able to identify five patients (0.6% of CD who had monosymptomatic presentation with musculoskeletal symptoms and signs in the form of bone pains, proximal myopathy, and fragility fractures without any gastrointestinal manifestation. All the five patients had severe MBD in the form of osteopenia, osteoporosis, and fragility fractures. Four of the five patients had additional risk factors such as antiepileptic drugs, chronic alcohol consumption, malnutrition, and associated vitamin D deficiency which might have contributed to the severity of MBD. Conclusion: Severe metabolic disease as the only presentation of CD is rare. Patients show significant improvement in clinical, biochemical, and radiological parameters with gluten-free diet, calcium, and vitamin D supplementation. CD should be looked for routinely in patients presenting with unexplained MBD.

Skeletal scintigraphy and quantitative tracer studies in metabolic bone disease

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Fogelman, Ignac

Bone scan imaging with the current bone seeking radiopharmaceuticals, the technetium-99m labelled diphosphonates, has dramatically improved our ability to evaluate skeletal pathology. In this thesis, chapter 1 presents a review of the history of bone scanning, summarises present concepts as to the mechanism of uptake of bone seeking agents and briefly illustrates the role of bone scanning in clinical practice. In chapter 2 the applications of bone scan imaging and quantitative tracer techniques derived from the bone scan in the detection of metabolic bone disease are discussed. Since skeletal uptake of Tc-99m diphosphonate depends upon skeletal metabolism one might expect that the bone scan would be of considerable value in the assessment of metabolic bone disease. However in these disorders the whole skeleton is often diffusely involved by the metabolic process and simple visual inspection of the scan image may not reveal the uniformly increased uptake of tracer. Certain patterns of bone scan abnormality have, however, been reported in patients with primary hyperparathyroidism and renal osteo-dystrophy; the present studies extend these observations and introduce the concept of "metabolic features" which are often recognisable in conditions with generalised increased bone turnover. As an aid to systematic recognition of these features on a given bone scan image a semi-quantitative scoring system, the metabolic index, was introduced. The metabolic index allowed differentiation between various groups of patients with metabolic disorders and a control population. In addition, in a bone scan study of patients with acromegaly, it was found that the metabolic index correlated well with disease activity as measured by serum growth hormone levels. The metabolic index was, however, found to be a relatively insensitive means of identifying disease in individual patients. Patients with increased bone turnover will have an absolute increase in skeletal uptake of tracer. As a

Genome-scale metabolic models applied to human health and disease.

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Cook, Daniel J; Nielsen, Jens

2017-11-01

Advances in genome sequencing, high throughput measurement of gene and protein expression levels, data accessibility, and computational power have allowed genome-scale metabolic models (GEMs) to become a useful tool for understanding metabolic alterations associated with many different diseases. Despite the proven utility of GEMs, researchers confront multiple challenges in the use of GEMs, their application to human health and disease, and their construction and simulation in an organ-specific and disease-specific manner. Several approaches that researchers are taking to address these challenges include using proteomic and transcriptomic-informed methods to build GEMs for individual organs, diseases, and patients and using constraints on model behavior during simulation to match observed metabolic fluxes. We review the challenges facing researchers in the use of GEMs, review the approaches used to address these challenges, and describe advances that are on the horizon and could lead to a better understanding of human metabolism. WIREs Syst Biol Med 2017, 9:e1393. doi: 10.1002/wsbm.1393 For further resources related to this article, please visit the WIREs website. © 2017 Wiley Periodicals, Inc.

Effects of Microencapsulated Synbiotic Administration at Different Dosages against heavy co-infection of White Spot Disease (WSD and Vibrio harveyi in Pacific White Shrimp (Litopenaeus vannamei

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Yunarty Yunarty

2016-12-01

Full Text Available White spot disease (WSD is one of infectious disease in shrimp caused by white spot syndrome virus (WSSV. This study aimed to determine the dosage immunological effects and growth performances of microencapsulated synbiotic (Bacillus NP5 and mannan oligosaccharide at different dosages on Pacific white shrimp.  The microencapsulated synbiotic   was administered as feed supplementation  against the co-infection of   WSSV and Vibrio harveyi. Synbiotic was encapsulated by spray drying method, further feed supplemented to Pacific white shrimp for 30 days at a  dosages of 0.5% (A, 1% (B, 2% (C and control treatments, i.e. without any microencapsulated synbiotic administration as positive control (D and negative control (E. The challenge test was performed on day 30 after feeding supplementation, then the experimental shrimps were injected by WSSV intramuscularly   at the infective dosage of 104 copies.-ml-1. Afterwards,   24 hours after WSSV injection the shrimps were immersed in water contained cells suspension of V. harveyi  at the cells population dosage of 106 CFU-.ml-1. All synbiotic treatments showed better results with the values of Total Haemocyte Count (THC, Phenoloxidase (PO and Respiratory Burst (RB, were higher (P<0.05 compared to positive control. The specific growth rates (SGR of A, B and C showed higher than both controls of D and E. The feed conversion ratio (FCR value of synbiotic treatments were lower (P<0.05 than both controls. However, the administration of microencapsulated synbiotic have not been able to prevent heavy impact of WSSV and V. harveyi co-infection due to lower SR and mortality pattern which continued to increase.   Keywords: Synbiotic, Litopenaeus vannamei, WSSV, Vibrio harveyi, co-infection

Occult Metabolic Bone Disease in Chronic Pancreatitis

African Journals Online (AJOL)

2017-10-26

Oct 26, 2017 ... KEYWORDS: Chronic pancreatitis, metabolic bone disease, osteomalacia, osteopenia ... with malabsorption, and endocrine dysfunction results in diabetes .... of insufficiency and deficiency were not assessed separately due ...

Metabolic Imaging in Parkinson Disease.

Science.gov (United States)

Meles, Sanne K; Teune, Laura K; de Jong, Bauke M; Dierckx, Rudi A; Leenders, Klaus L

2017-01-01

This review focuses on recent human 18 F-FDG PET studies in Parkinson disease. First, an overview is given of the current analytic approaches to metabolic brain imaging data. Next, we discuss how 18 F-FDG PET studies have advanced understanding of the relation between distinct brain regions and associated symptoms in Parkinson disease, including cognitive decline. In addition, the value of 18 F-FDG PET studies in differential diagnosis, identifying prodromal patients, and the evaluation of treatment effects are reviewed. Finally, anticipated developments in the field are addressed. © 2017 by the Society of Nuclear Medicine and Molecular Imaging.

Relative Handgrip Strength Is Inversely Associated with Metabolic Profile and Metabolic Disease in the General Population in China.

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Li, Dongxue; Guo, Guanghong; Xia, Lili; Yang, Xinghua; Zhang, Biao; Liu, Feng; Ma, Jingang; Hu, Zhiping; Li, Yajun; Li, Wei; Jiang, Jiajia; Gaisano, Herbert; Shan, Guangliang; He, Yan

2018-01-01

Background: Absolute handgrip strength has been correlated with metabolic profile and metabolic disease. Whether relative handgrip strength is also associated with metabolic disease has not been assessed. This study aimed at assessing the association of relative handgrip strength with metabolic profile and metabolic disease in the general population in China. Methods: Data were derived from an ongoing cross-sectional survey of the 2013 National Physical and Health in Shanxi Province, which involved 5520 participants. Multiple linear regression or multiple logistic regression analysis were used to assess the association of absolute/relative handgrip strength with the metabolic profile, preclinical, and established stages of metabolic diseases. Results: This study revealed that relative handgrip strength, that is when normalized to BMI, was associated with: (1) in both genders for more favorable blood lipid levels of high-density lipoprotein cholesterol [males: b = 0.19 (0.15, 0.23); females: b = 0.22 (0.17, 0.28)], low-density lipoprotein cholesterol [males: b = -0.14 (-0.23, -0.05); females: b = -0.19 (-0.31, -0.18)], triglycerides [males: b = -0.58 (-0.74, -0.43); females: b = -0.55 (-0.74, -0.36)] and total cholesterol [males: b = -0.20 (-0.31, -0.10); females: b = -0.19 (-0.32, -0.06)]; and better serum glucose levels in males [ b = -0.30 (-0.46, -0.15)]. (2) lower risk of impaired fasting glucose in males {third quartile [OR = 0.66 (0.45-0.95)] and fourth quartile [OR = 0.46 (0.30-0.71)] vs. first quartile} and dyslipidemia in both genders {third quartile [males: OR = 0.65 (0.48-0.87); females: OR = 0.68 (0.53-0.86)] and fourth quartile [males: OR = 0.47 (0.35-0.64); females: OR = 0.47(0.36-0.61)] vs. first quartile}. (3) lower risk of hyperlipidemia in both genders third quartile [males: OR = 0.66 (0.50-0.87); females: OR = 0.57 (0.43-0.75)] and fourth quartile [males: OR = 0.35 (0.26-0.47); females: OR = 0.51 (0.38-0.70)] vs. first quartile. However, contrary

A simple method of screening for metabolic bone disease

International Nuclear Information System (INIS)

Broughton, R.B.K.; Evans, W.D.

1982-01-01

The purpose of this investigation was to find a simple method -to be used as an adjunct to the conventional bone scintigram- that could differentiate between decreased bone metabolism or mass, i.e., osteoporosis -normal bone- and the group of conditions of increased bone metabolism or mass namely, osteomalacia, renal osteodystrophy, hyperparathyroidism and Paget's disease. The Fogelman's method using the bone to soft tissue ratios from region of interest analysis at 4 hours post injection, was adopted. An initial experience in measuring a value for the count rate density in lumbar vertebrae at 1 hr post injection during conventional bone scintigraphy appears to give a clear indication of the overall rate of bone metabolism. The advantage over whole body retention methods is that the scan performed at the end of the metabolic study will reveal localized bone disease that may otherwise not be anticipated

Cerebral glucose metabolism in Parkinson's disease

Energy Technology Data Exchange (ETDEWEB)

Martin, W R.W.; Beckman, J H; Calne, D B; Adam, M J; Harrop, R; Rogers, J G; Ruth, T J; Sayre, C I; Pate, B D [British Columbia Univ., Vancouver (Canada). TRIUMF Facility

1984-02-01

Local cerebral glucose utilization was measured in patients with predominantly unilateral Parkinson's disease using sup(18)F-2-fluoro-deoxyglucose and positron emission tomography. Preliminary results indicate the presence of asymmetric metabolic rates in the inferior basal ganglia. The structure comprising the largest portion of basal ganglia at this level is globus pallidus. These findings are consistent with metabolic studies on animals with unilateral nigrostriatal lesions in which pallidal hypermetabolism on the lesioned side has been demonstrated. Increased pallidal activity is likely secondary to a loss of inhibitory dopaminergic input to the striatum from substantia nigra.

Cerebral glucose metabolism in Parkinson's disease

International Nuclear Information System (INIS)

Martin, W.R.W.; Beckman, J.H.; Calne, D.B.; Adam, M.J.; Harrop, R.; Rogers, J.G.; Ruth, T.J.; Sayre, C.I.; Pate, B.D.

1984-01-01

Local cerebral glucose utilization was measured in patients with predominantly unilateral Parkinson's disease using sup(18)F-2-fluoro-deoxyglucose and positron emission tomography. Preliminary results indicate the presence of asymmetric metabolic rates in the inferior basal ganglia. The structure comprising the largest portion of basal ganglia at this level is globus pallidus. These findings are consistent with metabolic studies on animals with unilateral nigrostriatal lesions in which pallidal hypermetabolism on the lesioned side has been demonstrated. Increased pallidal activity is likely secondary to a loss of inhibitory dopaminergic input to the striatum from substantia nigra

Prevention of metabolic diseases: fruits (including fruit sugars) vs. vegetables.

Science.gov (United States)

Kuzma, Jessica N; Schmidt, Kelsey A; Kratz, Mario

2017-07-01

To discuss recent evidence from observational and intervention studies on the relationship between fruit and vegetable (F&V) consumption and metabolic disease. Observational studies have consistently demonstrated a modest inverse association between the intake of fruit and leafy green vegetables, but not total vegetables, and biomarkers of metabolic disease as well as incident type 2 diabetes mellitus. This is in contrast to limited evidence from recently published randomized controlled dietary intervention trials, which - in sum - suggests little to no impact of increased F&V consumption on biomarkers of metabolic disease. Evidence from observational studies that fruit and leafy green vegetable intake is associated with lower type 2 diabetes risk and better metabolic health could not be confirmed by dietary intervention trials. It is unclear whether this discrepancy is because of limitations inherent in observational studies (e.g., subjective dietary assessment methods, residual confounding) or due to limitations in the few available intervention studies (e.g., short duration of follow-up, interventions combining whole fruit and fruit juice, or lack of compliance). Future studies that attempt to address these limitations are needed to provide more conclusive insight into the impact of F&V consumption on metabolic health.

APP Metabolism Regulates Tau Proteostasis in Human Cerebral Cortex Neurons

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Steven Moore

2015-05-01

Full Text Available Accumulation of Aβ peptide fragments of the APP protein and neurofibrillary tangles of the microtubule-associated protein tau are the cellular hallmarks of Alzheimer’s disease (AD. To investigate the relationship between APP metabolism and tau protein levels and phosphorylation, we studied human-stem-cell-derived forebrain neurons with genetic forms of AD, all of which increase the release of pathogenic Aβ peptides. We identified marked increases in intracellular tau in genetic forms of AD that either mutated APP or increased its dosage, suggesting that APP metabolism is coupled to changes in tau proteostasis. Manipulating APP metabolism by β-secretase and γ-secretase inhibition, as well as γ-secretase modulation, results in specific increases and decreases in tau protein levels. These data demonstrate that APP metabolism regulates tau proteostasis and suggest that the relationship between APP processing and tau is not mediated solely through extracellular Aβ signaling to neurons.

APP metabolism regulates tau proteostasis in human cerebral cortex neurons.

Science.gov (United States)

Moore, Steven; Evans, Lewis D B; Andersson, Therese; Portelius, Erik; Smith, James; Dias, Tatyana B; Saurat, Nathalie; McGlade, Amelia; Kirwan, Peter; Blennow, Kaj; Hardy, John; Zetterberg, Henrik; Livesey, Frederick J

2015-05-05

Accumulation of Aβ peptide fragments of the APP protein and neurofibrillary tangles of the microtubule-associated protein tau are the cellular hallmarks of Alzheimer's disease (AD). To investigate the relationship between APP metabolism and tau protein levels and phosphorylation, we studied human-stem-cell-derived forebrain neurons with genetic forms of AD, all of which increase the release of pathogenic Aβ peptides. We identified marked increases in intracellular tau in genetic forms of AD that either mutated APP or increased its dosage, suggesting that APP metabolism is coupled to changes in tau proteostasis. Manipulating APP metabolism by β-secretase and γ-secretase inhibition, as well as γ-secretase modulation, results in specific increases and decreases in tau protein levels. These data demonstrate that APP metabolism regulates tau proteostasis and suggest that the relationship between APP processing and tau is not mediated solely through extracellular Aβ signaling to neurons. Copyright © 2015 The Authors. Published by Elsevier Inc. All rights reserved.

MECHANISMS IN ENDOCRINOLOGY: The sexually dimorphic role of androgens in human metabolic disease.

Science.gov (United States)

Schiffer, Lina; Kempegowda, Punith; Arlt, Wiebke; O'Reilly, Michael W

2017-09-01

Female androgen excess and male androgen deficiency manifest with an overlapping adverse metabolic phenotype, including abdominal obesity, insulin resistance, type 2 diabetes mellitus, non-alcoholic fatty liver disease and an increased risk of cardiovascular disease. Here, we review the impact of androgens on metabolic target tissues in an attempt to unravel the complex mechanistic links with metabolic dysfunction; we also evaluate clinical studies examining the associations between metabolic disease and disorders of androgen metabolism in men and women. We conceptualise that an equilibrium between androgen effects on adipose tissue and skeletal muscle underpins the metabolic phenotype observed in female androgen excess and male androgen deficiency. Androgens induce adipose tissue dysfunction, with effects on lipid metabolism, insulin resistance and fat mass expansion, while anabolic effects on skeletal muscle may confer metabolic benefits. We hypothesise that serum androgen concentrations observed in female androgen excess and male hypogonadism are metabolically disadvantageous, promoting adipose and liver lipid accumulation, central fat mass expansion and insulin resistance. © 2017 The authors.

Exploring metabolic dysfunction in chronic kidney disease

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Slee Adrian D

2012-04-01

Full Text Available Abstract Impaired kidney function and chronic kidney disease (CKD leading to kidney failure and end-stage renal disease (ESRD is a serious medical condition associated with increased morbidity, mortality, and in particular cardiovascular disease (CVD risk. CKD is associated with multiple physiological and metabolic disturbances, including hypertension, dyslipidemia and the anorexia-cachexia syndrome which are linked to poor outcomes. Specific hormonal, inflammatory, and nutritional-metabolic factors may play key roles in CKD development and pathogenesis. These include raised proinflammatory cytokines, such as interleukin-1 and −6, tumor necrosis factor, altered hepatic acute phase proteins, including reduced albumin, increased C-reactive protein, and perturbations in normal anabolic hormone responses with reduced growth hormone-insulin-like growth factor-1 axis activity. Others include hyperactivation of the renin-angiotensin aldosterone system (RAAS, with angiotensin II and aldosterone implicated in hypertension and the promotion of insulin resistance, and subsequent pharmacological blockade shown to improve blood pressure, metabolic control and offer reno-protective effects. Abnormal adipocytokine levels including leptin and adiponectin may further promote the insulin resistant, and proinflammatory state in CKD. Ghrelin may be also implicated and controversial studies suggest activities may be reduced in human CKD, and may provide a rationale for administration of acyl-ghrelin. Poor vitamin D status has also been associated with patient outcome and CVD risk and may indicate a role for supplementation. Glucocorticoid activities traditionally known for their involvement in the pathogenesis of a number of disease states are increased and may be implicated in CKD-associated hypertension, insulin resistance, diabetes risk and cachexia, both directly and indirectly through effects on other systems including activation of the mineralcorticoid

Chylomicrons metabolism in patients with coronary artery disease

International Nuclear Information System (INIS)

Brandizzi, Laura Ines Ventura

2002-01-01

Chylomicrons are the triglyceride-rich lipoproteins that carry dietary lipids absorbed in the intestine. In the bloodstream , chylomicron triglycerides are broken-down by lipoprotein lipase using apoliprotein (apo) CII as co factor. Fatty acids and glycerol resulting from the enzymatic action are absorbed and stored in the body tissues mainly adipose and muscle for subsequent utilizations energy source. The resulting triglycerides depleted remnants are taken-up by liver receptor such as the LDL receptor using mainly apo E as ligand. For methodological reasons, chylomicron metabolism has been unfrequently studied in subjects despite its pathophysiological importance, and this metabolism was not evaluated in the great clinical trials that established the link between atherosclerosis and lipids. In studies using oral fat load tests, it has been shown that in patients with coronary artery disease there is a trend to accumulation of post-prandial triglycerides, vitamin A or apo B-48 , suggesting that in those patients chylomicrons and their remnants are slowly removed from the circulation. A triglyceride-rich emulsion marked radioisotopic which mimics chylomicron metabolism when injected into the bloodstream has been described that can offer a more straight forward approach to evaluate chylomicrons. In coronary artery disease patients both lipolysis and remnant removal from the plasma of the chylomicron-like emulsions were found slowed-down compared with control subjects without the disease. The introduction of more practical techniques to assess chylomicron metabolism may be new mechanisms underlying atherogenesis. (author)

Relative Handgrip Strength Is Inversely Associated with Metabolic Profile and Metabolic Disease in the General Population in China

Directory of Open Access Journals (Sweden)

Dongxue Li

2018-02-01

Full Text Available Background: Absolute handgrip strength has been correlated with metabolic profile and metabolic disease. Whether relative handgrip strength is also associated with metabolic disease has not been assessed. This study aimed at assessing the association of relative handgrip strength with metabolic profile and metabolic disease in the general population in China.Methods: Data were derived from an ongoing cross-sectional survey of the 2013 National Physical and Health in Shanxi Province, which involved 5520 participants. Multiple linear regression or multiple logistic regression analysis were used to assess the association of absolute/relative handgrip strength with the metabolic profile, preclinical, and established stages of metabolic diseases.Results: This study revealed that relative handgrip strength, that is when normalized to BMI, was associated with: (1 in both genders for more favorable blood lipid levels of high-density lipoprotein cholesterol [males: b = 0.19 (0.15, 0.23; females: b = 0.22 (0.17, 0.28], low-density lipoprotein cholesterol [males: b = −0.14 (−0.23, −0.05; females: b = −0.19 (−0.31, −0.18], triglycerides [males: b = −0.58 (−0.74, −0.43; females: b = −0.55 (−0.74, −0.36] and total cholesterol [males: b = −0.20 (−0.31, −0.10; females: b = −0.19 (−0.32, −0.06]; and better serum glucose levels in males [b = −0.30 (−0.46, −0.15]. (2 lower risk of impaired fasting glucose in males {third quartile [OR = 0.66 (0.45–0.95] and fourth quartile [OR = 0.46 (0.30–0.71] vs. first quartile} and dyslipidemia in both genders {third quartile [males: OR = 0.65 (0.48–0.87; females: OR = 0.68 (0.53–0.86] and fourth quartile [males: OR = 0.47 (0.35–0.64; females: OR = 0.47(0.36–0.61] vs. first quartile}. (3 lower risk of hyperlipidemia in both genders third quartile [males: OR = 0.66 (0.50–0.87; females: OR = 0.57 (0.43–0.75] and fourth quartile [males: OR = 0.35 (0.26–0.47; females: OR

Metabolism features in the active rheumatoid disease

Energy Technology Data Exchange (ETDEWEB)

Cossermelli, W; Carvalho, N; Papaleo Netto, M [Sao Paulo Univ. (Brazil). Centro de Medicina Nuclear

1974-02-01

The /sup 131/I-labelled albumin metabolism was studied in fourteen female patients with rheumatoid arthritis. The half-life of distribution was increased while the turnover half-life and turnover rate was within normal limits. These results led to assume that synthesis and catabolism may not change this disease, not being the responsible mechanism of hypoalbuminemia. Hypoalbuminemia would appear as compensatory mechanism in view of other protein alterations, as hypergammaglobulinemia, without changes of stabilizing and metabolic properties of albumin, perhaps due to albumin molecular alterations.

Reappraisal of GIP Pharmacology for Metabolic Diseases

DEFF Research Database (Denmark)

Finan, Brian; Müller, Timo D; Clemmensen, Christoffer

2016-01-01

Glucagon-like peptide-1 (GLP-1) analogs are considered the best current medicines for type 2 diabetes (T2D) and obesity due to their actions in lowering blood glucose and body weight. Despite similarities to GLP-1, glucose-dependent insulinotropic polypeptide (GIP) has not been extensively pursue...... be beneficial for metabolic diseases. However, a growing body of new evidence - including data based on refined genetically modified models and improved pharmacological agents - suggests a paradigm shift on how the GIP system should be manipulated for metabolic benefits....

Metabolism features in the active rheumatoid disease

International Nuclear Information System (INIS)

Cossermelli, W.; Carvalho, N.; Papaleo Netto, M.

1974-01-01

It was studied the 131 I-labelled albumin metabolism in fourteen female patients with rheumatoid arthritis. The half-life of distribution was increased while the turnover half-life and turnover rate was within normal limits. These results led to assume that synthesis and catabolism may not change this disease, not being the responsible mechanism of hypoalbuminemia. Hypoalbuminemia would appear as compensatory mechanism in view of other protein alterations, as hypergammaglobulinemia, without changes of stabilizing and metabolic properties of albumin, perhaps due to albumin molecular alterations [pt

Mitochondrial dysfunction and cellular metabolic deficiency in Alzheimer's disease.

Science.gov (United States)

Gu, Xue-Mei; Huang, Han-Chang; Jiang, Zhao-Feng

2012-10-01

Alzheimer's disease (AD) is an age-related neurodegenerative disorder. The pathology of AD includes amyloid-β (Aβ) deposits in neuritic plaques and neurofibrillary tangles composed of hyperphosphorylated tau, as well as neuronal loss in specific brain regions. Increasing epidemiological and functional neuroimaging evidence indicates that global and regional disruptions in brain metabolism are involved in the pathogenesis of this disease. Aβ precursor protein is cleaved to produce both extracellular and intracellular Aβ, accumulation of which might interfere with the homeostasis of cellular metabolism. Mitochondria are highly dynamic organelles that not only supply the main energy to the cell but also regulate apoptosis. Mitochondrial dysfunction might contribute to Aβ neurotoxicity. In this review, we summarize the pathways of Aβ generation and its potential neurotoxic effects on cellular metabolism and mitochondrial dysfunction.

Metabolic Dysfunction in Parkinson's Disease: Bioenergetics, Redox Homeostasis and Central Carbon Metabolism.

Science.gov (United States)

Anandhan, Annadurai; Jacome, Maria S; Lei, Shulei; Hernandez-Franco, Pablo; Pappa, Aglaia; Panayiotidis, Mihalis I; Powers, Robert; Franco, Rodrigo

2017-07-01

The loss of dopaminergic neurons in the substantia nigra pars compacta (SNpc) and the accumulation of protein inclusions (Lewy bodies) are the pathological hallmarks of Parkinson's disease (PD). PD is triggered by genetic alterations, environmental/occupational exposures and aging. However, the exact molecular mechanisms linking these PD risk factors to neuronal dysfunction are still unclear. Alterations in redox homeostasis and bioenergetics (energy failure) are thought to be central components of neurodegeneration that contribute to the impairment of important homeostatic processes in dopaminergic cells such as protein quality control mechanisms, neurotransmitter release/metabolism, axonal transport of vesicles and cell survival. Importantly, both bioenergetics and redox homeostasis are coupled to neuro-glial central carbon metabolism. We and others have recently established a link between the alterations in central carbon metabolism induced by PD risk factors, redox homeostasis and bioenergetics and their contribution to the survival/death of dopaminergic cells. In this review, we focus on the link between metabolic dysfunction, energy failure and redox imbalance in PD, making an emphasis in the contribution of central carbon (glucose) metabolism. The evidence summarized here strongly supports the consideration of PD as a disorder of cell metabolism. Copyright © 2017 Elsevier Inc. All rights reserved.

Pupillometry as an indicator of L-DOPA dosages in Parkinson's disease patients.

Science.gov (United States)

Bartošová, O; Bonnet, C; Ulmanová, O; Šíma, M; Perlík, F; Růžička, E; Slanař, O

2018-04-01

Dopamine was shown to induce mydriasis by excitation of alpha-adrenergic receptors at the dilator pupillae muscle. Pupilla diameter may thus serve as an indirect measure of peripheral pharmacokinetics of L-DOPA and dopamine. The aim of this study is to evaluate the effect of L-DOPA dosage on pupillometric parameters in Parkinson's disease (PD) patients. Sixteen PD patients and 14 healthy control subjects (CS) were studied. The statistical analysis revealed significant differences between CS and PD patients for the mean maximum and minimum pupil diameters (p = 0.017, p = 0.028, respectively), with higher values found in PD. Moreover, a significant dose-response relationship was found between the maximum pupil diameter and both the morning L-DOPA dose (R 2  = 0.78) and the total daily L-DOPA dose (R 2  = 0.93). A sigmoid-shaped curve best describes the dose-response relationship, with a ceiling effect at about 400 mg L-DOPA daily dose. In conclusion, measuring pupillometric parameters represents a sensitive tool for non-invasive evaluation of the peripheral effect of L-DOPA, especially with daily doses below 400 mg L-DOPA.

Metabolic disorders and nutritional status in autoimmune thyroid diseases

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Anna Kawicka

2015-01-01

Full Text Available In recent years, the authors of epidemiological studies have documented that autoimmune diseases are a major problem of modern society and are classified as diseases of civilization. Autoimmune thyroid diseases (ATDs are caused by an abnormal immune response to autoantigens present in the thyroid gland – they often coexist with other autoimmune diseases. The most common dysfunctions of the thyroid gland are hypothyroidism, Graves-Basedow disease and Hashimoto’s disease. Hashimoto’s thyroiditis can be the main cause of primary hypothyroidism of the thyroid gland. Anthropometric, biochemical and physicochemical parameters are used to assess the nutritional status during the diagnosis and treatment of thyroid diseases. Patients with hypothyroidism are often obese, whereas patients with hyperthyroidism are often afflicted with rapid weight loss. The consequence of obesity is a change of the thyroid hormones’ activity; however, weight reduction leads to their normalization. The activity and metabolic rate of thyroid hormones are modifiable. ATDs are associated with abnormalities of glucose metabolism and thus increased risk of developing diabetes mellitus type 1 and type 2. Celiac disease (CD also increases the risk of developing other autoimmune diseases. Malnutrition or the presence of numerous nutritional deficiencies in a patient’s body can be the cause of thyroid disorders. Coexisting deficiencies of such elements as iodine, iron, selenium and zinc may impair the function of the thyroid gland. Other nutrient deficiencies usually observed in patients suffering from ATD are: protein deficiencies, vitamin deficiencies (A, C, B6, B5, B1 and mineral deficiencies (phosphorus, magnesium, potassium, sodium, chromium. Proper diet helps to reduce the symptoms of the disease, maintains a healthy weight and prevents the occurrence of malnutrition. This article presents an overview of selected documented studies and scientific reports on the

[Metabolic disorders and nutritional status in autoimmune thyroid diseases].

Science.gov (United States)

Kawicka, Anna; Regulska-Ilow, Bożena; Regulska-Ilow, Bożena

2015-01-02

In recent years, the authors of epidemiological studies have documented that autoimmune diseases are a major problem of modern society and are classified as diseases of civilization. Autoimmune thyroid diseases (ATDs) are caused by an abnormal immune response to autoantigens present in the thyroid gland - they often coexist with other autoimmune diseases. The most common dysfunctions of the thyroid gland are hypothyroidism, Graves-Basedow disease and Hashimoto's disease. Hashimoto's thyroiditis can be the main cause of primary hypothyroidism of the thyroid gland. Anthropometric, biochemical and physicochemical parameters are used to assess the nutritional status during the diagnosis and treatment of thyroid diseases. Patients with hypothyroidism are often obese, whereas patients with hyperthyroidism are often afflicted with rapid weight loss. The consequence of obesity is a change of the thyroid hormones' activity; however, weight reduction leads to their normalization. The activity and metabolic rate of thyroid hormones are modifiable. ATDs are associated with abnormalities of glucose metabolism and thus increased risk of developing diabetes mellitus type 1 and type 2. Celiac disease (CD) also increases the risk of developing other autoimmune diseases. Malnutrition or the presence of numerous nutritional deficiencies in a patient's body can be the cause of thyroid disorders. Coexisting deficiencies of such elements as iodine, iron, selenium and zinc may impair the function of the thyroid gland. Other nutrient deficiencies usually observed in patients suffering from ATD are: protein deficiencies, vitamin deficiencies (A, C, B6, B5, B1) and mineral deficiencies (phosphorus, magnesium, potassium, sodium, chromium). Proper diet helps to reduce the symptoms of the disease, maintains a healthy weight and prevents the occurrence of malnutrition. This article presents an overview of selected documented studies and scientific reports on the relationship of metabolic

Founders lecture 2007. Metabolic bone disease: what has changed in 30 years?

Energy Technology Data Exchange (ETDEWEB)

Sundaram, Murali [Cleveland Clinic, Diagnostic Radiology, MSK, Cleveland, OH (United States)

2009-09-15

To provide an update on imaging of metabolic bone disease based on new developments, findings, and changing practices over the past 30 years. Literature review of osteoporosis, osteomalacia, renal osteodystrophy, Paget's disease, bisphosphonates, with an emphasis on imaging. Cited references and pertinent findings. Significant developments have occurred in the imaging of metabolic bone disease over the past 30 years. (orig.)

Plasma levels and symptom complaints in patients maintained on daily dosage of methadone hydrochloride.

Science.gov (United States)

Horns, W H; Rado, M; Goldstein, A

1975-06-01

Plasma methadone levels, symptom complaints, and urine tests for illicit opiate use were followed weekly in 17 patients on a methadone maintenance program. There were very large differences between patients in the plasma level established at a given dosage, implying large differences in the rate of methadone metabolism. Despite virtually constant daily dosage, the plasma methadone levels fluctuated greatly from week to week and from day to day in individual patients. With rate exceptions there was no relationship between plasma methadone level and symptom complaints or between weekly chamges in plasma methadone level and changes in symptom complaints. Except possible to identify the ocassional patient with unusually low plasam methadone levels, the determination of methadone levels is not likely to be or practical value in methadone programs.

Associations between Zinc Deficiency and Metabolic Abnormalities in Patients with Chronic Liver Disease

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Takashi Himoto

2018-01-01

Full Text Available Zinc (Zn is an essential trace element which has favorable antioxidant, anti-inflammatory, and apoptotic effects. The liver mainly plays a crucial role in maintaining systemic Zn homeostasis. Therefore, the occurrence of chronic liver diseases, such as chronic hepatitis, liver cirrhosis, or fatty liver, results in the impairment of Zn metabolism, and subsequently Zn deficiency. Zn deficiency causes plenty of metabolic abnormalities, including insulin resistance, hepatic steatosis and hepatic encephalopathy. Inversely, metabolic abnormalities like hypoalbuminemia in patients with liver cirrhosis often result in Zn deficiency. Recent studies have revealed the putative mechanisms by which Zn deficiency evokes a variety of metabolic abnormalities in chronic liver disease. Zn supplementation has shown beneficial effects on such metabolic abnormalities in experimental models and actual patients with chronic liver disease. This review summarizes the pathogenesis of metabolic abnormalities deriving from Zn deficiency and the favorable effects of Zn administration in patients with chronic liver disease. In addition, we also highlight the interactions between Zn and other trace elements, vitamins, amino acids, or hormones in such patients.

MR imaging of metabolic white matter diseases: Therapeutic response

International Nuclear Information System (INIS)

Gebarski, S.S.; Allen, R.

1987-01-01

In metabolic diseases affecting the brain, MR imaging abnormalities include white-matter signal aberrations suggesting myelination delay, dysmyelination and demyelination, pathologic iron storage, and finally, loss of substance usually in a nonspecific pattern. The authors suggest that MR imaging may have therapeutic implications: (1) classic galactosemia - white-matter signal aberration became normal after dietary therapy; (2) phenylketonuria - age- and sex-matched treated and nontreated adolescents showed marked differences in brain volume, with the treated patient's volume nearly normal; (3) maple syrup urine disease - gross white-matter signal aberration became nearly normal after dietary therapy; and (4) hyperglycinemia - relentless progression of white-matter signal aberration and loss of brain substance despite therapy. These data suggest that brain MR imaging may provide a therapeutic index in certain metabolic diseases

Metabolic effects of obesity causing disease in childhood.

Science.gov (United States)

Abrams, Pamela; Levitt Katz, Lorraine E

2011-02-01

Childhood obesity is rising to epidemic proportions throughout the world, and much emphasis has been placed on the long-term consequences that can result later, in adulthood. This article reviews the metabolic consequences of obesity that can manifest as disease during the childhood years. Obese children suffer from many disease processes once thought to affect only adults. They can have type 2 diabetes mellitus, and potentially early β cell failure with rapid progression to an insulin requirement. There is a high prevalence of fatty liver disease in obese children, and complications such as steatohepatitis and even cirrhosis can develop during childhood. Visceral fat has been shown to have many different properties than subcutaneous fat, and children with central adiposity can develop the metabolic syndrome with insulin resistance, hypertension, and dyslipidemia. Hyperandrogenism, sleep disturbances, and many types of orthopedic complications can also develop in young children. Physicians should not only warn obese children and their families about the long-term consequences of obesity for which they are at risk in adulthood, they should also screen for the many diseases that may already be present.

Impact of the gut microbiota on inflammation, obesity, and metabolic disease.

Science.gov (United States)

Boulangé, Claire L; Neves, Ana Luisa; Chilloux, Julien; Nicholson, Jeremy K; Dumas, Marc-Emmanuel

2016-04-20

The human gut harbors more than 100 trillion microbial cells, which have an essential role in human metabolic regulation via their symbiotic interactions with the host. Altered gut microbial ecosystems have been associated with increased metabolic and immune disorders in animals and humans. Molecular interactions linking the gut microbiota with host energy metabolism, lipid accumulation, and immunity have also been identified. However, the exact mechanisms that link specific variations in the composition of the gut microbiota with the development of obesity and metabolic diseases in humans remain obscure owing to the complex etiology of these pathologies. In this review, we discuss current knowledge about the mechanistic interactions between the gut microbiota, host energy metabolism, and the host immune system in the context of obesity and metabolic disease, with a focus on the importance of the axis that links gut microbes and host metabolic inflammation. Finally, we discuss therapeutic approaches aimed at reshaping the gut microbial ecosystem to regulate obesity and related pathologies, as well as the challenges that remain in this area.

Mechanistic modeling of aberrant energy metabolism in human disease

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Vineet eSangar

2012-10-01

Full Text Available Dysfunction in energy metabolism—including in pathways localized to the mitochondria—has been implicated in the pathogenesis of a wide array of disorders, ranging from cancer to neurodegenerative diseases to type II diabetes. The inherent complexities of energy and mitochondrial metabolism present a significant obstacle in the effort to understand the role that these molecular processes play in the development of disease. To help unravel these complexities, systems biology methods have been applied to develop an array of computational metabolic models, ranging from mitochondria-specific processes to genome-scale cellular networks. These constraint-based models can efficiently simulate aspects of normal and aberrant metabolism in various genetic and environmental conditions. Development of these models leverages—and also provides a powerful means to integrate and interpret—information from a wide range of sources including genomics, proteomics, metabolomics, and enzyme kinetics. Here, we review a variety of mechanistic modeling studies that explore metabolic functions, deficiency disorders, and aberrant biochemical pathways in mitochondria and related regions in the cell.

Dietary Treatment of Metabolic Acidosis in Chronic Kidney Disease.

Science.gov (United States)

Siener, Roswitha

2018-04-20

Chronic kidney disease and reduced glomerular filtration rate are risk factors for the development of chronic metabolic acidosis. The prevention or correction of chronic metabolic acidosis has been found to slow progression of chronic kidney disease. Dietary composition can strongly affect acid⁻base balance. Major determinants of net endogenous acid production are the generation of large amounts of hydrogen ions, mostly by animal-derived protein, which is counterbalanced by the metabolism of base-producing foods like fruits and vegetables. Alkali therapy of chronic metabolic acidosis can be achieved by providing an alkali-rich diet or oral administration of alkali salts. The primary goal of dietary treatment should be to increase the proportion of fruits and vegetables and to reduce the daily protein intake to 0.8⁻1.0 g per kg body weight. Diet modifications should begin early, i.e., even in patients with moderate kidney impairment, because usual dietary habits of many developed societies contribute an increased proportion of acid equivalents due to the high intake of protein from animal sources.

Dietary Treatment of Metabolic Acidosis in Chronic Kidney Disease

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Roswitha Siener

2018-04-01

Full Text Available Chronic kidney disease and reduced glomerular filtration rate are risk factors for the development of chronic metabolic acidosis. The prevention or correction of chronic metabolic acidosis has been found to slow progression of chronic kidney disease. Dietary composition can strongly affect acid–base balance. Major determinants of net endogenous acid production are the generation of large amounts of hydrogen ions, mostly by animal-derived protein, which is counterbalanced by the metabolism of base-producing foods like fruits and vegetables. Alkali therapy of chronic metabolic acidosis can be achieved by providing an alkali-rich diet or oral administration of alkali salts. The primary goal of dietary treatment should be to increase the proportion of fruits and vegetables and to reduce the daily protein intake to 0.8–1.0 g per kg body weight. Diet modifications should begin early, i.e., even in patients with moderate kidney impairment, because usual dietary habits of many developed societies contribute an increased proportion of acid equivalents due to the high intake of protein from animal sources.

Nutritional and metabolic diseases involving the nervous system.

Science.gov (United States)

Kopcha, M

1987-03-01

This article will discuss eight diseases that alter normal nervous system function: hypovitaminosis A, water deprivation/salt toxicity, ammonia toxicosis, hypomagnesemia, hypocalcemia, nervous ketosis, hepatoencephalopathy, and rumen metabolic acidosis.

Metabolic Syndrome: Systems Thinking in Heart Disease.

Science.gov (United States)

Dommermuth, Ron; Ewing, Kristine

2018-03-01

Metabolic syndrome (MetS) is a cluster of cardiometabolic risk factors. MetS is associated with approximately 4-fold increase in the likelihood of developing type 2 diabetes mellitus (T2DM) and a 2-fold increase in the incidence of cardiovascular disease complications. MetS is a progressive, proinflammatory, prothrombotic condition that manifests itself along a broad spectrum of disease. It is associated with hypertension, obstructive sleep apnea, fatty liver disease, gout, and polycystic ovarian syndrome. Intervening in and reversing the pathologic process become more difficult as the disease progresses, highlighting the needs for increased individual and community surveillance and primary prevention. Copyright © 2017 Elsevier Inc. All rights reserved.

Skeletal muscle metabolism during prolonged exercise in Pompe disease

DEFF Research Database (Denmark)

Preisler, Nicolai; Laforêt, Pascal; Madsen, Karen Lindhardt

2017-01-01

OBJECTIVE: Pompe disease (glycogenosis type II) is caused by lysosomal alpha-glucosidase deficiency, which leads to a block in intra-lysosomal glycogen breakdown. In spite of enzyme replacement therapy, Pompe disease continues to be a progressive metabolic myopathy. Considering the health benefits...... of exercise, it is important in Pompe disease to acquire more information about muscle substrate use during exercise. METHODS: Seven adults with Pompe disease were matched to a healthy control group (1:1). We determined (1) peak oxidative capacity (VO2peak) and (2) carbohydrate and fatty acid metabolism...... during submaximal exercise (33 W) for 1 h, using cycle-ergometer exercise, indirect calorimetry and stable isotopes. RESULTS: In the patients, VO2peak was less than half of average control values; mean difference -1659 mL/min (CI: -2450 to -867, P = 0.001). However, the respiratory exchange ratio...

Prevalence of non alcoholic fatty liver disease in patients with metabolic syndrome

International Nuclear Information System (INIS)

Iftikhar, R.; Kamran, S.M.

2015-01-01

To determine frequency of Non Alcoholic fatty liver disease in patients with Metabolic Syndrome (MetS). Study Design: Cross sectional study. Place and Duration of Study: Department of medicine, CMH Okara, Jan 2013 to July 2013. Patients and Methods: We included 491 adult males, diagnosed with metabolic syndrome (MetS), presenting in outpatient department for routine review. MetS was diagnosed as per the International Diabetes Federation (IDF) proposed criteria of 2004. Detailed history and examination of each individual was done and data entered in pre designed performa. Brightness and posterior attenuation on ultrasound abdomen were considered indices for fatty liver disease in presence of elevated ALT, negative hepatitis serology and absence of alcohol intake. All the data was analyzed using SPSS version 16. p value of less than 0.05 was considered statistically significant. Results: Out of 491 participants with MetS, 222 (45.2%) had fatty liver disease. Mean BMI in patients with metabolic syndrome was 26.1 (± .89) and mean BMI in fatty liver patients was 27.3 (± 0.67). Out of total 5 components of Mets, patients with fatty liver disease had 3.24 (± 0.25) components, as compared to 2.1 (± 0.34) in whole of study group. Conclusion: A large number of patients with metabolic syndrome have fatty liver disease. Fatty liver disease is more frequent in patients who are overweight and those having multiple risk factors of metabolic syndrome. (author)

Metabolic Bone Disease in the Bariatric Surgery Patient

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Susan E. Williams

2011-01-01

Full Text Available Bariatric surgery has proven to be a life-saving measure for some, but for others it has precipitated a plethora of metabolic complications ranging from mild to life-threatening, sometimes to the point of requiring surgical revision. Obesity was previously thought to be bone protective, but this is indeed not the case. Morbidly obese individuals are at risk for metabolic bone disease (MBD due to chronic vitamin D deficiency, inadequate calcium intake, sedentary lifestyle, chronic dieting, underlying chronic diseases, and the use of certain medications used to treat those diseases. After bariatric surgery, the risk for bone-related problems is even greater, owing to severely restricted intake, malabsorption, poor compliance with prescribed supplements, and dramatic weight loss. Patients presenting for bariatric surgery should be evaluated for MBD and receive appropriate presurgical interventions. Furthermore, every patient who has undergone bariatric surgery should receive meticulous lifetime monitoring, as the risk for developing MBD remains ever present.

Gaucher disease type I: assessment of basal metabolic rate in patients from southern Brazil.

Science.gov (United States)

Doneda, Divair; Lopes, André L; Oliveira, Alvaro R; Netto, Cristina B; Moulin, Cileide C; Schwartz, Ida V D

2011-01-15

Gaucher disease (GD) is characterized by clinical heterogeneity and is associated with metabolic abnormalities such as increased resting energy expenditure. To assess the basal metabolic rate (BMR) of patients with GD type I followed at the Gaucher Disease Reference Center of Rio Grande do Sul, Brazil. Fourteen patients (male=6) and 14 healthy controls matched by gender, age and body mass index (BMI) were included in the study. The nutritional status of patients was assessed by BMI. The BMR was measured by indirect calorimetry. In two patients, it was possible to perform BMR in the pre- and the post-treatment periods. Mean age and BMI of patients and controls were, respectively, 32.8 ± 17.6 and 32.1 ± 16.6 years and 23.3 ± 3.1 and 22.4 ± 3.1 kg/m(2). Twelve patients were receiving enzyme replacement therapy (ERT) with imiglucerase (mean duration of treatment=5.2 ± 4.3 years; mean dosage of imiglucerase=24.2 ± 7.3 UI/kg/inf). Five patients (36%) were overweight, and nine (64%) were normal weight. Mean BMR of patients on ERT was 27.1% higher than that of controls (p=0.007). There was no difference between the BMR of patients on ERT and not on ERT (n=4) (p=0.92). Comparing the BMR of patients on ERT and their controls with the BMR estimated by the Harris-Benedict equation, the BMR of patients was 6.3% higher than the estimated (p = 0.1), while the BMR of their controls was 17.0% lower than the estimated (p = 0.001). Most treated GD type I patients were normal weight. The patients including those on ERT showed higher BMR when compared to controls. Imiglucerase is probably unable to normalize the hypermetabolism presented by GD type I patients. Additional studies should be performed to confirm our findings. Copyright © 2010 Elsevier Inc. All rights reserved.

A possible method using baseline hormonal levels to prescribe the appropriate oral therapeutic radioiodine dosage for Graves' disease

International Nuclear Information System (INIS)

Nakajo, Masayuki; Tsuchimochi, Shinsaku; Jinguji, Megumi; Tanabe, Hiroaki; Umanodan, Tomoichi; Nakabeppu, Yoshiaki

2007-01-01

The purpose of this study was to retrospectively examine the correlations of hormonal ratios with radioiodine I-131 therapeutic parameters and the potentiality of prescribing the therapeutic I-131 target dosage for an individual patient with Graves' disease using baseline serum levels of thyroid hormones. Serum T3, T4, and FT4 levels 6 and 12 months after I-131 therapy/baseline levels (hormonal ratios) were calculated for a total of 68 therapeutic courses in 57 patients with Graves' disease. The therapeutic parameters were absorbed dose (Gy), dose concentration (μCi/g) and oral dose (mCi). Linear regression analysis was performed for correlating hormonal ratios (X) and therapeutic parameters (Y). Significant (P<0.05) negative correlations of the hormonal ratios were observed with absorbed dose (R -0.50 for T3, -0.61 for T4, and -0.46 for FT4 at 6 months, and -0.29 for T3, -0.44 for T4 at 12 months) and dose concentration (R -0.57 for T3, -0.58 for T4, and -0.49 for FT4 at 6 months and -0.27 for T3, -0.27 for T4 at 12 months), but not with oral dose at 6 months and 12 months or the absorbed dose and dose concentration for FT4 at 12 months. The correlations were higher at 6 months than at 12 months and in serum T4 than in serum T3 and FT4. The formulae for serum T4 at 6 months were as follows: Y (Gy)=109-53X and Y (μCi/g)=109-52X. These results suggest that the hormonal ratios are significantly correlated with the absorbed dose and dose concentration. The formulae for serum T4 at 6 months may serve to prescribe the individual oral dosage for Graves' disease, although the correlation coefficients are about -0.6. (author)

Differential glucose metabolism in mice and humans affected by McArdle disease

DEFF Research Database (Denmark)

Krag, Thomas O; Pinós, Tomàs; Nielsen, Tue L

2016-01-01

McArdle disease (muscle glycogenosis type V) is a disease caused by myophosphorylase deficiency leading to "blocked" glycogen breakdown. A significant but varying glycogen accumulation in especially distal hind limb muscles of mice affected by McArdle disease has recently been demonstrated......, which could lead to lower glycogen accumulation. In comparison, tibialis anterior, extensor digitorum longus, and soleus had massive glycogen accumulation, but few, if any, changes or adaptations in glucose metabolism compared with wild-type mice. The findings suggest plasticity in glycogen metabolism....... In this study, we investigated how myophosphorylase deficiency affects glucose metabolism in hind limb muscle of 20-wk-old McArdle mice and vastus lateralis muscles from patients with McArdle disease. Western blot analysis and activity assay demonstrated that glycogen synthase was inhibited in glycolytic muscle...

The association of serum leptin levels with metabolic diseases

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Jen-Pi Tsai

2017-01-01

Full Text Available Leptin is a 167-amino-acid protein released by white adipose tissue and encoded by the obese gene. It has a role as a negative regulator of appetite control through sending a satiety signal to act on receptors within the hypothalamus. At normal levels, leptin can exert its effects on weight regulation according to white fat mass, induce sodium excretion, maintain vascular tone, and repair the myocardium. Beyond these effects, elevated serum leptin levels have been implicated in the pathogenesis of metabolic syndrome, diabetes mellitus, hypertension, and multiple cardiovascular diseases. In addition, hyperleptinemia had been reported to contribute to renal diseases through multiple mechanisms resulting in glomerulopathy presenting with a decreased glomerular filtration rate, increased albuminuria, and related clinical symptoms, which are pathophysiological features of chronic kidney disease. Because these cardiovascular and metabolic disorders are great challenges for physicians, understanding the related pathophysiological association with leptin might become a valuable aid in handling patients in daily clinical practice. This review will discuss the roles of leptin in the regulation of biological functions of multiple organs beyond the maintenance of feeding and metabolism.

The role of IL6 in liver cancer linked to metabolic liver disease ...

International Development Research Centre (IDRC) Digital Library (Canada)

The role of IL6 in liver cancer linked to metabolic liver disease. Liver cancer is highly fatal, it has very few treatment options, and it is one of the few cancers whose incidence is rising worldwide. One poorly understood risk factor for liver cancer is obesity/metabolic disease (such as diabetes and fatty liver disease).

Krüppel-Like Factors in Metabolic Homeostasis and Cardiometabolic Disease

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Yumiko Oishi

2018-06-01

Full Text Available Members of the Krüppel-like factor (KLF family of transcription factors, which are characterized by the presence of three conserved Cys2/His2 zinc-fingers in their C-terminal domains, control a wide variety of biological processes. In particular, recent studies have revealed that KLFs play diverse and essential roles in the control of metabolism at the cellular, tissue and systemic levels. In both liver and skeletal muscle, KLFs control glucose, lipid and amino acid metabolism so as to coordinate systemic metabolism in the steady state and in the face of metabolic stresses, such as fasting. The functions of KLFs within metabolic tissues are also important contributors to the responses to injury and inflammation within those tissues. KLFs also control the function of immune cells, such as macrophages, which are involved in the inflammatory processes underlying both cardiovascular and metabolic diseases. This review focuses mainly on the physiological and pathological functions of KLFs in the liver and skeletal muscle. The involvement of KLFs in inflammation in these tissues is also summarized. We then discuss the implications of KLFs' control of metabolism and inflammation in cardiometabolic diseases.

Metabolomics reveals metabolic biomarkers of Crohn's disease

Energy Technology Data Exchange (ETDEWEB)

Jansson, J.K.; Willing, B.; Lucio, M.; Fekete, A.; Dicksved, J.; Halfvarson, J.; Tysk, C.; Schmitt-Kopplin, P.

2009-06-01

The causes and etiology of Crohn's disease (CD) are currently unknown although both host genetics and environmental factors play a role. Here we used non-targeted metabolic profiling to determine the contribution of metabolites produced by the gut microbiota towards disease status of the host. Ion Cyclotron Resonance Fourier Transform Mass Spectrometry (ICR-FT/MS) was used to discern the masses of thousands of metabolites in fecal samples collected from 17 identical twin pairs, including healthy individuals and those with CD. Pathways with differentiating metabolites included those involved in the metabolism and or synthesis of amino acids, fatty acids, bile acids and arachidonic acid. Several metabolites were positively or negatively correlated to the disease phenotype and to specific microbes previously characterized in the same samples. Our data reveal novel differentiating metabolites for CD that may provide diagnostic biomarkers and/or monitoring tools as well as insight into potential targets for disease therapy and prevention.

Metabolic Effects of Obesity and Its Interaction with Endocrine Diseases.

Science.gov (United States)

Clark, Melissa; Hoenig, Margarethe

2016-09-01

Obesity in pet dogs and cats is a significant problem in developed countries, and seems to be increasing in prevalence. Excess body fat has adverse metabolic consequences, including insulin resistance, altered adipokine secretion, changes in metabolic rate, abnormal lipid metabolism, and fat accumulation in visceral organs. Obese cats are predisposed to endocrine and metabolic disorders such as diabetes and hepatic lipidosis. A connection likely also exists between obesity and diabetes mellitus in dogs. No system has been developed to identify obese pets at greatest risk for development of obesity-associated metabolic diseases, and further study in this area is needed. Copyright © 2016 Elsevier Inc. All rights reserved.

The study on risk factor of metabolic diseases in pancreatic steatosis

Energy Technology Data Exchange (ETDEWEB)

Cho, Jin Young; Ye, Soo Young; Kim, Dong Hyun [Dept. of Radiological Science, College of Health Sciences, Catholic University of Pusan, Busan (Korea, Republic of)

2016-03-15

The body of the fat tissue increased in obese represented by risk factors such as cardiovascular diseases, diabetes, metabolic disease and dyslipidemia. Such metabolic diseases and the like of the cardiovascular and cerebrovascular disease, hypertension, dyslipidemia, increase in the adipose tissue of the pancreas is known to be a risk factor of these diseases. Study on the diagnosis and treatment of pancreatic cancer was conducted actively, case studies on pancreatic steatosis is not much. In this study, divided into a control group diagnosed with pancreatic steatosis as a result of ultrasonography to evaluation the physical characteristics and serologic tests and blood pressure and arterial stiffness. The control group and the test pancreas steatosis age and waist circumference, body mass index, total cholesterol, HDL cholesterol, LDL cholesterol, and systolic and diastolic blood pressure, fasting blood glucose, arterial elasticity is higher in pancreatic steatosis. And the lower ankle brachial stenosis and HDLcholesterol were lower than the normal control group, so the pancreatic steatosis harmful to blood vessels.(P <0.05). The difference between the control group and it was confirmed that the pancreatic jibanggun statistically significant. In conclusion, pancreatic steatosis at abdominal ultrasound can predict the risk of metabolic diseases, and there was a correlation with cardiovascular disease.

The study on risk factor of metabolic diseases in pancreatic steatosis

International Nuclear Information System (INIS)

Cho, Jin Young; Ye, Soo Young; Kim, Dong Hyun

2016-01-01

The body of the fat tissue increased in obese represented by risk factors such as cardiovascular diseases, diabetes, metabolic disease and dyslipidemia. Such metabolic diseases and the like of the cardiovascular and cerebrovascular disease, hypertension, dyslipidemia, increase in the adipose tissue of the pancreas is known to be a risk factor of these diseases. Study on the diagnosis and treatment of pancreatic cancer was conducted actively, case studies on pancreatic steatosis is not much. In this study, divided into a control group diagnosed with pancreatic steatosis as a result of ultrasonography to evaluation the physical characteristics and serologic tests and blood pressure and arterial stiffness. The control group and the test pancreas steatosis age and waist circumference, body mass index, total cholesterol, HDL cholesterol, LDL cholesterol, and systolic and diastolic blood pressure, fasting blood glucose, arterial elasticity is higher in pancreatic steatosis. And the lower ankle brachial stenosis and HDLcholesterol were lower than the normal control group, so the pancreatic steatosis harmful to blood vessels.(P <0.05). The difference between the control group and it was confirmed that the pancreatic jibanggun statistically significant. In conclusion, pancreatic steatosis at abdominal ultrasound can predict the risk of metabolic diseases, and there was a correlation with cardiovascular disease

Inherited metabolic liver diseases in infants and children: an overview

Directory of Open Access Journals (Sweden)

Ivo Barić

2013-10-01

Full Text Available Inborn errors of metabolism, which affect the liver are a large, continuously increasing group of diseases. Their clinical onset can occur at any age, from intrauterine period presenting as liver failure already at birth to late adulthood. Inherited metabolic disorders must be considered in differential diagnosis of every unexplained liver disease. Specific diagnostic work-up for either their confirmation or exclusion should start immediately since any postponing can result in delayed diagnosis and death or irreversible disability. This can be particularly painful while many inherited metabolic liver diseases are relatively easily treatable if diagnosed on time, for instance galactosemia or hereditary fructose intolerance by simple dietary means. Any unexplained liver disease, even one looking initially benign, should be considered as a potential liver failure and therefore should deserve proper attention. Diagnosis in neonates is additionally complicated because of the factors which can mask liver disease, such as physiological neonatal jaundice, normally relatively enlarged liver and increased transaminases at that age. In everyday practice, in order to reveal the etiology, it is useful to classify and distinguish some clinical patterns which, together with a few routine, widely available laboratory tests (aminotransferases, prothrombine time, albumin, gammaGT, total and conjugated bilirubin, ammonia, alkaline phosphatase and glucose make the search for the cause much easier. These patterns are isolated hyperbilirubinemia, syndrome of cholestasis in early infancy, hepatocellular jaundice, Reye syndrome, portal cirrhosis and isolated hepatomegaly. Despite the fact that some diseases can present with more than one pattern (for instance, alpha-1-antitrypsin deficiency as infantile cholestasis, but also as hepatocellular jaundice, and that in some disesases one pattern can evolve into another (for instance, Wilson disease from hepatocellular

Who's your daddy?: paternal inheritance of metabolic disease risk.

Science.gov (United States)

Isganaitis, Elvira; Suehiro, Harumi; Cardona, Connie

2017-02-01

Although the importance of optimizing mothers' health prior to conception and during pregnancy is now well accepted, recent data also implicate health and nutritional status of fathers as contributors to chronic disease risk in their progeny. This brief review will highlight recent epidemiological and experimental studies linking paternal overnutrition, undernutrition, and other forms of stress, to metabolic disease in the offspring. The past 2 years have brought tremendous insights into the mechanisms by which paternal exposures can contribute to disease susceptibility in the next generation. Recent data, both from humans and experimental models, demonstrate that paternal obesity and undernutrition result in epigenetic reprogramming of male germ cells, notably altered DNA methylation, histone retention, and expression of small noncoding RNAs and transfer RNA fragments. Novel mechanisms have also been identified, such as epididymal transport vesicles, seminal fluid hormones and metabolites, and a unique seminal fluid microbiome. Paternal nutritional and other perturbations are linked to risk of metabolic disease and obesity in offspring. Germ cell-dependent mechanisms have recently been linked to these intergenerational effects. Nongenetic, paternal inheritance of chronic disease has important implications for public health, and may provide novel opportunities for multigenerational disease prevention.

Nutrigenetics and Metabolic Disease: Current Status and Implications for Personalised Nutrition

Science.gov (United States)

Phillips, Catherine M.

2013-01-01

Obesity, particularly central adiposity, is the primary causal factor in the development of insulin resistance, the hallmark of the metabolic syndrome (MetS), a common condition characterized by dyslipidaemia and hypertension, which is associated with increased risk of cardiovascular disease (CVD) and type 2 diabetes (T2DM). Interactions between genetic and environmental factors such as diet and lifestyle, particularly over-nutrition and sedentary behavior, promote the progression and pathogenesis of these polygenic diet-related diseases. Their current prevalence is increasing dramatically to epidemic proportions. Nutrition is probably the most important environmental factor that modulates expression of genes involved in metabolic pathways and the variety of phenotypes associated with obesity, the MetS and T2DM. Furthermore, the health effects of nutrients may be modulated by genetic variants. Nutrigenomics and nutrigenetics require an understanding of nutrition, genetics, biochemistry and a range of “omic” technologies to investigate the complex interaction between genetic and environmental factors relevant to metabolic health and disease. These rapidly developing fields of nutritional science hold much promise in improving nutrition for optimal personal and public health. This review presents the current state of the art in nutrigenetic research illustrating the significance of gene-nutrient interactions in the context of metabolic disease. PMID:23306188

Nutrigenetics and Metabolic Disease: Current Status and Implications for Personalised Nutrition

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Catherine M. Phillips

2013-01-01

Full Text Available Obesity, particularly central adiposity, is the primary causal factor in the development of insulin resistance, the hallmark of the metabolic syndrome (MetS, a common condition characterized by dyslipidaemia and hypertension, which is associated with increased risk of cardiovascular disease (CVD and type 2 diabetes (T2DM. Interactions between genetic and environmental factors such as diet and lifestyle, particularly over-nutrition and sedentary behavior, promote the progression and pathogenesis of these polygenic diet-related diseases. Their current prevalence is increasing dramatically to epidemic proportions. Nutrition is probably the most important environmental factor that modulates expression of genes involved in metabolic pathways and the variety of phenotypes associated with obesity, the MetS and T2DM. Furthermore, the health effects of nutrients may be modulated by genetic variants. Nutrigenomics and nutrigenetics require an understanding of nutrition, genetics, biochemistry and a range of “omic” technologies to investigate the complex interaction between genetic and environmental factors relevant to metabolic health and disease. These rapidly developing fields of nutritional science hold much promise in improving nutrition for optimal personal and public health. This review presents the current state of the art in nutrigenetic research illustrating the significance of gene-nutrient interactions in the context of metabolic disease.

Nutrigenetics and metabolic disease: current status and implications for personalised nutrition.

Science.gov (United States)

Phillips, Catherine M

2013-01-10

Obesity, particularly central adiposity, is the primary causal factor in the development of insulin resistance, the hallmark of the metabolic syndrome (MetS), a common condition characterized by dyslipidaemia and hypertension, which is associated with increased risk of cardiovascular disease (CVD) and type 2 diabetes (T2DM). Interactions between genetic and environmental factors such as diet and lifestyle, particularly over-nutrition and sedentary behavior, promote the progression and pathogenesis of these polygenic diet-related diseases. Their current prevalence is increasing dramatically to epidemic proportions. Nutrition is probably the most important environmental factor that modulates expression of genes involved in metabolic pathways and the variety of phenotypes associated with obesity, the MetS and T2DM. Furthermore, the health effects of nutrients may be modulated by genetic variants. Nutrigenomics and nutrigenetics require an understanding of nutrition, genetics, biochemistry and a range of "omic" technologies to investigate the complex interaction between genetic and environmental factors relevant to metabolic health and disease. These rapidly developing fields of nutritional science hold much promise in improving nutrition for optimal personal and public health. This review presents the current state of the art in nutrigenetic research illustrating the significance of gene-nutrient interactions in the context of metabolic disease.

Meta-analysis : High-dosage vitamin E supplementation may increase all-cause mortality

NARCIS (Netherlands)

Miller, ER; Pastor-Barriuso, R; Dalal, D; Riemersma, RA; Appel, LJ; Guallar, E

2005-01-01

Background: Experimental models and observational studies suggest that vitamin E supplementation may prevent cardiovascular disease and cancer. However, several trials of high-dosage vitamin E supplementation showed non-statistically significant increases in total mortality. Purpose: To perform a

Association Between Newborn Metabolic Profiles and Pediatric Kidney Disease

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Manish M. Sood

2018-05-01

Full Text Available Introduction: Metabolomics offers considerable promise in early disease detection. We set out to test the hypothesis that routine newborn metabolic profiles at birth, obtained through screening for inborn errors of metabolism, would be associated with kidney disease and add incremental information to known clinical risk factors. Methods: We conducted a population-level cohort study in Ontario, Canada, using metabolic profiles from 1,288,905 newborns from 2006 to 2015. The primary outcome was chronic kidney disease (CKD or dialysis. Individual metabolites and their ratio combinations were examined by logistic regression after adjustment for established risk factors for kidney disease and incremental risk prediction measured. Results: CKD occurred in 2086 (0.16%, median time 612 days and dialysis in 641 (0.05%, median time 99 days infants and children. Individual metabolites consisted of amino acids, acylcarnitines, markers of fatty acid oxidation, and others. Base models incorporating clinical risk factors only provided c-statistics of 0.61 for CKD and 0.70 for dialysis. The addition of identified metabolites to risk prediciton models resulted in significant incremental improvement in the performance of both models (CKD model: c-statistic 0.66 NRI 0.36 IDI 0.04, dialysis model: c-statistic 0.77 NRI 0.57 IDI 0.09. This was consistent after internal validation using bootstrapping and a sensitivity analysis excluding outcomes within the first 30 days. Conclusion: Routinely collected screening metabolites at birth are associated with CKD and the need for dialytic therapies in infants and children, and add incremental information to traditional clinical risk factors. Keywords: chronic kidney disease, dialysis, end-stage kidney disease, metabolomics, newborn screening, pediatric, renal failure

Effectiveness of several dosage formula of oil and nano emulsion of citronella against vascular streak dieback (VSD) disease on cocoa

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Noveriza, R.; Trisno, J.; Rahma, H.; Yuliani, S.; Reflin; Martinius

2018-02-01

The disease of Vascular streak dieback (VSD) is a deadly disease of cocoa plants, because it attacks the vascular tissue of cocoa at growing point of the plant. In West Sumatra the disease was first reported in 2015 with an incidence of disease range 58.82% - 100% and an intensity of disease range 24.29% - 44.7%. The purpose of this study was to examine the effectiveness of dosage application of oil formula and nano emulsion of citronella formula against Vascular streak dieback (VSD) disease on cocoa plants in West Sumatra (in Padang Pariaman District and Limapuluh Kota District). The results showed that the percentage of VSD disease attacks in both testing sites was 100%. The oil and nano emulsion of citronella formulas can reduce the intensity of VSD disease on cocoa plants in West Sumatra, particularly in Padang Pariaman District and Limapuluh Kota District. The reduction of VSD intensity in Padang Pariaman district ranged from 8.32 to 21.13%; while in Limapuluh Kota district ranged from 4.33 to 11.80%. The nano emulsion of citronella formulation is effective to suppress the intensity of VSD disease on cocoa plants at doses 0.1% (≥ 30% of effectiveness level).

The Role of Dietary Inflammatory Index in Cardiovascular Disease, Metabolic Syndrome and Mortality

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Miguel Ruiz-Canela

2016-08-01

Full Text Available Inflammation is an underlying pathophysiological process in chronic diseases, such as obesity, type 2 diabetes mellitus and cardiovascular disease. In fact, a number of systematic reviews have shown the association between inflammatory biomarkers, such as CRP, IL-1β, IL-6, TNF-α, IL-4, or IL-10, and cardio-metabolic diseases. Diet is one of the main lifestyle-related factors which modulates the inflammatory process. Different individual foods and dietary patterns can have a beneficial health effect associated with their anti-inflammatory properties. The dietary inflammatory index (DII was recently developed to estimate the inflammatory potential of overall diet. The aim of this review is to examine the findings of recent papers that have investigated the association between the DII, cardio-metabolic risk factors and cardiovascular disease. The relevance of the DII score in the association between inflammation and cardio-metabolic diseases is critically appraised, as well as its role in the context of healthy dietary patterns. We conclude that the DII score seems to be a useful tool to appraise the inflammatory capacity of the diet and to better understand the relationships between diet, inflammation, and cardio-metabolic diseases.

Chronic obstructive pulmonary disease candidate gene prioritization based on metabolic networks and functional information.

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Xinyan Wang

Full Text Available Chronic obstructive pulmonary disease (COPD is a multi-factor disease, in which metabolic disturbances played important roles. In this paper, functional information was integrated into a COPD-related metabolic network to assess similarity between genes. Then a gene prioritization method was applied to the COPD-related metabolic network to prioritize COPD candidate genes. The gene prioritization method was superior to ToppGene and ToppNet in both literature validation and functional enrichment analysis. Top-ranked genes prioritized from the metabolic perspective with functional information could promote the better understanding about the molecular mechanism of this disease. Top 100 genes might be potential markers for diagnostic and effective therapies.

Development of a metabolic biosignature for detection of early Lyme disease.

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Molins, Claudia R; Ashton, Laura V; Wormser, Gary P; Hess, Ann M; Delorey, Mark J; Mahapatra, Sebabrata; Schriefer, Martin E; Belisle, John T

2015-06-15

Early Lyme disease patients often present to the clinic prior to developing a detectable antibody response to Borrelia burgdorferi, the etiologic agent. Thus, existing 2-tier serology-based assays yield low sensitivities (29%-40%) for early infection. The lack of an accurate laboratory test for early Lyme disease contributes to misconceptions about diagnosis and treatment, and underscores the need for new diagnostic approaches. Retrospective serum samples from patients with early Lyme disease, other diseases, and healthy controls were analyzed for small molecule metabolites by liquid chromatography-mass spectrometry (LC-MS). A metabolomics data workflow was applied to select a biosignature for classifying early Lyme disease and non-Lyme disease patients. A statistical model of the biosignature was trained using the patients' LC-MS data, and subsequently applied as an experimental diagnostic tool with LC-MS data from additional patient sera. The accuracy of this method was compared with standard 2-tier serology. Metabolic biosignature development selected 95 molecular features that distinguished early Lyme disease patients from healthy controls. Statistical modeling reduced the biosignature to 44 molecular features, and correctly classified early Lyme disease patients and healthy controls with a sensitivity of 88% (84%-95%), and a specificity of 95% (90%-100%). Importantly, the metabolic biosignature correctly classified 77%-95% of the of serology negative Lyme disease patients. The data provide proof-of-concept that metabolic profiling for early Lyme disease can achieve significantly greater (P Diseases Society of America. All rights reserved. For Permissions, please e-mail: journals.permissions@oup.com.

Questions from the clinician to the radiologist regarding the diagnosis of metabolic bone diseases

Energy Technology Data Exchange (ETDEWEB)

Schulz, W.; Schmidt, M.

1986-12-01

Macromorphological X-ray findings in metabolic bone diseases can be established only in advanced stages. Micromorphological X-ray diagnostic procedures will support the diagnosis even in early stages. Mineralometric examinations are adjuvant methods for early diagnosis and survey of therapy in metabolic bone diseases. The synopsis of parameters of calcium phosphate metabolism, bone histology (histomorphometry) and radiological morphology enables the type and stage of osteopathy to be diagnosed. The supplementary diagnostic methods are helpful in distinguishing bone diseases with increased turnover, inpaired bone modelling and absorption, disturbed mineralization and ectopic calcification. Within the metabolic osteopathies, osteoporosis is gaining more and more importance as a socioeconomic problem; therefore, early diagnosis and treatment are of significant relevance. Hyper-, hypoparathyroidism and osteoidosis are diseases at can be cured if diagnosed early.

Questions from the clinician to the radiologist regarding the diagnosis of metabolic bone diseases

International Nuclear Information System (INIS)

Schulz, W.; Schmidt, M.; Klinikum Bamberg

1986-01-01

Macromorphological X-ray findings in metabolic bone diseases can be established only in advanced stages. Micromorphological X-ray diagnostic procedures will support the diagnosis even in early stages. Mineralometric examinations are adjuvant methods for early diagnosis and survey of therapy in metabolic bone diseases. The synopsis of parameters of calcium phosphate metabolism, bone histology (histomorphometry) and radiological morphology enables the type and stage of osteopathy to be diagnosed. The supplementary diagnostic methods are helpful in distinguishing bone diseases with increased turnover, inpaired bone modelling and absorption, disturbed mineralization and ectopic calcification. Within the metabolic osteopathies, osteoporosis is gaining more and more importance as a socioeconomic problem; therefore, early diagnosis and treatment are of significant relevance. Hyper-, hypoparathyroidism and osteoidosis are diseases at can be cured if diagnosed early. (orig.) [de

Circadian rhythms and metabolic syndrome: from experimental genetics to human disease.

Science.gov (United States)

Maury, Eleonore; Ramsey, Kathryn Moynihan; Bass, Joseph

2010-02-19

The incidence of the metabolic syndrome represents a spectrum of disorders that continue to increase across the industrialized world. Both genetic and environmental factors contribute to metabolic syndrome and recent evidence has emerged to suggest that alterations in circadian systems and sleep participate in the pathogenesis of the disease. In this review, we highlight studies at the intersection of clinical medicine and experimental genetics that pinpoint how perturbations of the internal clock system, and sleep, constitute risk factors for disorders including obesity, diabetes mellitus, cardiovascular disease, thrombosis and even inflammation. An exciting aspect of the field has been the integration of behavioral and physiological approaches, and the emerging insight into both neural and peripheral tissues in disease pathogenesis. Consideration of the cell and molecular links between disorders of circadian rhythms and sleep with metabolic syndrome has begun to open new opportunities for mechanism-based therapeutics.

Fat and carbohydrate metabolism during exercise in late-onset Pompe disease

DEFF Research Database (Denmark)

Preisler, Nicolai; Laforet, Pascal; Madsen, Karen Lindhardt

2012-01-01

forearm exercise testing, and peak work capacity was determined. Fat and carbohydrate metabolism during cycle exercise was examined with a combination of indirect calorimetry and stable isotope methodology. Finally, the effects of an IV glucose infusion on heart rate, ratings of perceived exertion...... examined the metabolic response to exercise in patients with late-onset Pompe disease, in order to determine if a defect in energy metabolism may play a role in the pathogenesis of Pompe disease. We studied six adult patients with Pompe disease and 10 healthy subjects. The participants underwent ischemic......, and work capacity during exercise were determined. We found that peak oxidative capacity was reduced in the patients to 17.6 vs. 38.8 ml kg(-1) min(-1) in healthy subjects (p = 0.002). There were no differences in the rate of appearance and rate of oxidation of palmitate, or total fat and carbohydrate...

Histone dosage regulates DNA damage sensitivity in a checkpoint-independent manner by the homologous recombination pathway

Science.gov (United States)

Liang, Dun; Burkhart, Sarah Lyn; Singh, Rakesh Kumar; Kabbaj, Marie-Helene Miquel; Gunjan, Akash

2012-01-01

In eukaryotes, multiple genes encode histone proteins that package genomic deoxyribonucleic acid (DNA) and regulate its accessibility. Because of their positive charge, ‘free’ (non-chromatin associated) histones can bind non-specifically to the negatively charged DNA and affect its metabolism, including DNA repair. We have investigated the effect of altering histone dosage on DNA repair in budding yeast. An increase in histone gene dosage resulted in enhanced DNA damage sensitivity, whereas deletion of a H3–H4 gene pair resulted in reduced levels of free H3 and H4 concomitant with resistance to DNA damaging agents, even in mutants defective in the DNA damage checkpoint. Studies involving the repair of a HO endonuclease-mediated DNA double-strand break (DSB) at the MAT locus show enhanced repair efficiency by the homologous recombination (HR) pathway on a reduction in histone dosage. Cells with reduced histone dosage experience greater histone loss around a DSB, whereas the recruitment of HR factors is concomitantly enhanced. Further, free histones compete with the HR machinery for binding to DNA and associate with certain HR factors, potentially interfering with HR-mediated repair. Our findings may have important implications for DNA repair, genomic stability, carcinogenesis and aging in human cells that have dozens of histone genes. PMID:22850743

Effect of metabolic alkalosis on respiratory function in patients with chronic obstructive lung disease.

Science.gov (United States)

Bear, R.; Goldstein, M.; Phillipson, E.; Ho, M.; Hammeke, M.; Feldman, R.; Handelsman, S.; Halperin, M.

1977-01-01

Eleven instances of a mixed acid-base disorder consisting of chronic respiratory acidosis and metabolic alkalosis were recognized in eight patients with chronic obstructive lung disease and carbon dioxide retention. Correction of the metabolic alkalosis led to substantial improvement in blood gas values and clinical symptoms. Patients with mixed chronic respiratory acidosis and metabolic alkalosis constitute a common subgroup of patients with chronic obstructive lung disease and carbon dioxide retention; these patients benefit from correction of the metabolic alkalosis. PMID:21028

FGF21 as a hepatokine, adipokine, and myokine in metabolism and diseases

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Nobuyuki eItoh

2014-07-01

Full Text Available Fibroblast growth factor (FGF family members are mostly secreted as signaling proteins with diverse functions in development and metabolism. FGF21 is a unique FGF with metabolic, but not proliferative activities. FGF21 is mostly induced by different kinds of stress and acts though FGF receptor 1c with β−Klotho as a cofactor in an endocrine or, in parts, autocirne/paracrine manner. Hepatic FGF21 directly acts on white adipocytes to inhibit lipolysis and acts through the brain to increase systemic glucocorticoid levels and suppress physical activity in response to starvation. It also protects against dioxin toxicity. Adipocytic FGF21 induces the browning of white adipose tissue (WAT and activates brown adipocytes in response to cold exposure. It also acts as an upstream effector of adiponectin in white adipocytes. Myocytic FGF21 protects against diet-induced obesity and insulin resistance, induces the browning of WAT, and protects against cardiac hypertrophy. In addition, Fgf21 polymorphisms are possibly related with metabolic diseases and FGF21 are biomarker of metabolic diseases. These findings indicate that FGF21 plays roles as a hepatokine, adipokine, and myokine in metabolism, injury protection, and diseases.

Therapeutic potential of Mediator complex subunits in metabolic diseases.

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Ranjan, Amol; Ansari, Suraiya A

2018-01-01

The multisubunit Mediator is an evolutionary conserved transcriptional coregulatory complex in eukaryotes. It is needed for the transcriptional regulation of gene expression in general as well as in a gene specific manner. Mediator complex subunits interact with different transcription factors as well as components of RNA Pol II transcription initiation complex and in doing so act as a bridge between gene specific transcription factors and general Pol II transcription machinery. Specific interaction of various Mediator subunits with nuclear receptors (NRs) and other transcription factors involved in metabolism has been reported in different studies. Evidences indicate that ligand-activated NRs recruit Mediator complex for RNA Pol II-dependent gene transcription. These NRs have been explored as therapeutic targets in different metabolic diseases; however, they show side-effects as targets due to their overlapping involvement in different signaling pathways. Here we discuss the interaction of various Mediator subunits with transcription factors involved in metabolism and whether specific interaction of these transcription factors with Mediator subunits could be potentially utilized as therapeutic strategy in a variety of metabolic diseases. Copyright © 2017 Elsevier B.V. and Société Française de Biochimie et Biologie Moléculaire (SFBBM). All rights reserved.

The effectiveness of metformin in patients with metabolic syndrome and nonalcoholic fatty liver disease

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S A Butrova

2008-06-01

Full Text Available The mechanism of action of metformin is realized through activation of cAMP-dependent protein kinase, leading to a decrease hepatic glucose production as well as to decrease the synthesis of triglycerides and an increase in fat oxidation. Several studies have demonstrated the positive effect of the drug in non-alcoholic fatty liver disease, manifested in reducing the activity of enzymes, reducing the size of the liver and insulin resistance. The aim of our study was to evaluate the effectiveness of metformin in patients with metabolic syndrome and nonalcoholic fatty liver disease. The study found that the use Siofor 850 mg 2 times a day in conjunction with a reduced-calorie nutrition in patients with metabolic syndrome and nonalcoholic fatty liver disease leads to a significant reduction in insulin resistance associated with decreased activity of transaminases, improvement of metabolic parameters. The therapy Siofor majority of patients (60% with metabolic syndrome and nonalcoholic fatty liver disease achieved a clinically significant weight loss and improved body composition. Application Siofor improves lifestyle changes in obese patients with non-alcoholic liver disease dirovoy and metabolic disorders.

Lipidomics: Novel insight into the biochemical mechanism of lipid metabolism and dysregulation-associated disease.

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Zhao, Ying-Yong; Miao, Hua; Cheng, Xian-Long; Wei, Feng

2015-10-05

The application of lipidomics, after genomics, proteomics and metabolomics, offered largely opportunities to illuminate the entire spectrum of lipidome based on a quantitative or semi-quantitative level in a biological system. When combined with advances in proteomics and metabolomics high-throughput platforms, lipidomics provided the opportunity for analyzing the unique roles of specific lipids in complex cellular processes. Abnormal lipid metabolism was demonstrated to be greatly implicated in many human lifestyle-related diseases. In this review, we focused on lipidomic applications in brain injury disease, cancer, metabolic disease, cardiovascular disease, respiratory disease and infectious disease to discover disease biomarkers and illustrate biochemical metabolic pathways. We also discussed the analytical techniques, future perspectives and potential problems of lipidomic applications. The application of lipidomics in disease biomarker discovery provides the opportunity for gaining novel insights into biochemical mechanism. Copyright © 2015 Elsevier Ireland Ltd. All rights reserved.

[Adiponectin in patients with metabolic syndrome and diseases of the liver, bile ducts and pancreas].

Science.gov (United States)

Vašura, Adam; Blaho, Martin; Dítě, Petr; Kupka, Tomáš; Svoboda, Pavel; Martínek, Arnošt

Epidemiological data show that the metabolic syndrome can be diagnosed in up to 30 % of the population. Regarding 5 components of the metabolic syndrome, three of them, in case of positivity (visceral obesity, arterial hypertension, hypertriglyceridemia, changes of HDL-cholesterol levels and type 2 diabetes mellitus), are pathogenic factors which are the most frequently related to cardiovascular diseases, but currently they are also the focus of interest for gastroenterologists. The relationship between non-alcoholic hepatic steatosis, including non-alcoholic steatohepatitis, has been described. Less is known so far about the relation to the pancreas disease, particularly with respect to the status referred to as non-alcoholic fatty pancreas disease. The hormone selectively produced by adipose tissue is adiponectin. This protein is studied as a possible biomarker in people with metabolic syndrome, including obesity. Besides that, there is a question studied whether adiponectin can also play a significant role in the pathogenesis of diseases associated with fat building up in parenchymatous organs. Finding a reliable biomarker for patients with metabolic syndrome or diseases of the liver, biliary system and pancreas in relation to metabolic syndrome, presents a big challenge. And adiponectin is one of the promising biomarkers.Key words: adiponectin - biliary disease - metabolic syndrome - pancreatic steatosis - steatohepatitis.

Impact of Weight Regain on Metabolic Disease Risk: A Review of Human Trials

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Cynthia M. Kroeger

2014-01-01

Full Text Available Dietary restriction interventions are effective for weight loss and reduction of chronic disease risk. Unfortunately, most people tend to regain much of this lost weight within one year after intervention. While some studies suggest that minor degrees of weight regain have no effect on metabolic disease risk parameters, other studies demonstrate a complete reversal in metabolic benefits. In light of these conflicting findings, it is of interest to determine how complete weight maintenance versus mild weight regain affects key risk parameters. These findings would have important clinical implications, as they could help identify a weight regain threshold that could preserve the metabolic benefits of weight loss. Accordingly, this review examined the impact of no weight regain versus mild regain on various metabolic disease risk parameters, including plasma lipids, blood pressure, glucose, and insulin concentrations, in adult subjects.

A benefit/risk approach towards selecting appropriate pharmaceutical dosage forms - an application for paediatric dosage form selection.

Science.gov (United States)

Sam, Tom; Ernest, Terry B; Walsh, Jennifer; Williams, Julie L

2012-10-05

The design and selection of new pharmaceutical dosage forms involves the careful consideration and balancing of a quality target product profile against technical challenges and development feasibility. Paediatric dosage forms present particular complexity due to the diverse patient population, patient compliance challenges and safety considerations of this vulnerable population. This paper presents a structured framework for assessing the comparative benefits and risks of different pharmaceutical design options against pre-determined criteria relating to (1) efficacy, (2) safety and (3) patient access. This benefit/risk framework has then been applied to three hypothetical, but realistic, scenarios for paediatric dosage forms in order to explore its utility in guiding dosage form design and formulation selection. The approach allows a rigorous, systematic and qualitative assessment of the merits and disadvantages of each dosage form option and helps identify mitigating strategies to modify risk. The application of a weighting and scoring system to the criteria depending on the specific case could further refine the analysis and aid decision-making. In this paper, one case study is scored for illustrative purposes. However, it is acknowledged that in real development scenarios, the generation of actual data considering the very specific situation for the patient/product/developer would come into play to drive decisions on the most appropriate dosage form strategy. Copyright © 2012 Elsevier B.V. All rights reserved.

Rasagiline (TVP-1012): a new selective monoamine oxidase inhibitor for Parkinson's disease.

Science.gov (United States)

Guay, David R P

2006-12-01

This article reviews the chemistry, pharmacodynamics, pharmacokinetics, clinical efficacy, tolerability, drug-interaction potential, indications, dosing, and potential role of rasagiline mesylate, a new selective monoamine oxidase (MAO) type B (MAO-B) inhibitor, in the treatment of Parkinson's disease. A MEDLINE/PUBMED search (1986 through September 2006) was conducted to identify studies involving rasagiline written in English. Additional references were obtained from the bibliographies of these studies. All studies evaluating any aspect of rasagiline, including in vitro, in vivo (animal), and human studies, were reviewed. Rasagiline mesylate was developed with the goal of producing a selective MAO-B inhibitor that is not metabolized to (presumed) toxic metabolites (eg, amphetamine and methamphetamine, which are byproducts of the metabolism of selegiline, another selective MAO-B inhibitor). In vitro and in vivo data have confirmed the drug's selectivity for MAO-B. Rasagiline is almost completely eliminated by oxidative metabolism (catalyzed by cytochrome P-450 [CYP] isozyme 1A2) followed by renal excretion of conjugated parent compound and metabolites. Drug clearance is sufficiently slow to allow once-daily dosing. Several studies have documented its efficacy as monotherapy for early-stage disease and as adjunctive therapy in L-dopa recipients with motor fluctuations. As monotherapy, rasagiline is well tolerated with an adverse-effect profile similar to that of placebo. As adjunctive therapy, it exhibits the expected adverse effects of dopamine excess, which can be ameliorated by reducing the L-dopa dosage. CYP1A2 inhibitors slow the elimination of rasagiline and mandate dosage reduction. Hepatic impairment has an analogous effect. The recommended dosage regimens for monotherapy and adjunctive therapy are 1 and 0.5 mg PO QD, respectively. Despite the well-documented selectivity of rasagiline, the manufacturer recommends virtually all of the dietary (vis

Perfusion and metabolism imaging studies in Parkinson's disease

DEFF Research Database (Denmark)

Borghammer, Per

2012-01-01

Positron emission tomography (PET) and single photon emission computed tomography (SPECT) are important tools in the evaluation of brain blood flow and glucose metabolism in Parkinson's disease (PD). However, conflicting results are reported in the literature depending on the type of imaging data...

Glutathione Metabolism and Parkinson’s Disease

OpenAIRE

Smeyne, Michelle; Smeyne, Richard Jay

2013-01-01

It has been established that oxidative stress, defined as the condition when the sum of free radicals in a cell exceeds the antioxidant capacity of the cell, contributes to the pathogenesis of Parkinson’s disease. Glutathione is a ubiquitous thiol tripeptide that acts alone, or in concert with enzymes within cells to reduce superoxide radicals, hydroxyl radicals and peroxynitrites. In this review, we examine the synthesis, metabolism and functional interactions of glutathione, and discuss how...

Manipulating the Circadian and Sleep Cycles to Protect Against Metabolic Disease

OpenAIRE

Nohara, Kazunari; Yoo, Seung-Hee; Chen, Zheng (Jake)

2015-01-01

Modernization of human society parallels an epidemic of metabolic disorders including obesity. Apart from excess caloric intake, a 24/7 lifestyle poses another important challenge to our metabolic health. Recent research under both laboratory and epidemiological settings has indicated that abnormal temporal organization of sleep and wakeful activities including food intake is a significant risk factor for metabolic disease. The circadian clock system is our intrinsic biological timer that reg...

HFE gene mutations and Wilson's disease in Sardinia.

Science.gov (United States)

Sorbello, Orazio; Sini, Margherita; Civolani, Alberto; Demelia, Luigi

2010-03-01

Hypocaeruloplasminaemia can lead to tissue iron storage in Wilson's disease and the possibility of iron overload in long-term overtreated patients should be considered. The HFE gene encodes a protein that is intimately involved in intestinal iron absorption. The aim of this study was to determine the prevalence of the HFE gene mutation, its role in iron metabolism of Wilson's disease patients and the interplay of therapy in copper and iron homeostasis. The records of 32 patients with Wilson's disease were reviewed for iron and copper indices, HFE gene mutations and liver biopsy. Twenty-six patients were negative for HFE gene mutations and did not present significant alterations of iron metabolism. The HFE mutation was significantly associated with increased hepatic iron content (PHFE gene wild-type. The HFE gene mutations may be an addictional factor in iron overload in Wilson's disease. Our results showed that an adjustment of dosage of drugs could prevent further iron overload induced by overtreatment only in patients HFE wild-type. 2009. Published by Elsevier Ltd.

A prospective study of monitoring practices for metabolic disease in antipsychotic-treated community psychiatric patients

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Watkinson Helen MO

2007-06-01

Full Text Available Abstract Background Patients with severe mental illness are at increased risk for metabolic and cardiovascular disease. A number of recent guidelines and consensus statements recommend stringent monitoring of metabolic function in individuals receiving antipsychotic drugs. Methods We conducted a prospective cohort study of 106 community-treated psychiatric patients from across the diagnostic spectrum from the Northeast of England to investigate changes in metabolic status and monitoring practices for metabolic and cardiovascular disease. We undertook detailed anthropometric and metabolic assessment at baseline and follow-up, and examined clinical notes and hospital laboratory records to ascertain monitoring practices. Results A high prevalence of undiagnosed and untreated metabolic disease was present at baseline assessment. Mean follow-up time was 599.3 (SD ± 235.4 days. Body mass index (p 50% of subjects had neither blood glucose nor lipids monitored during the follow-up period. Conclusion This cohort has a high prevalence of metabolic disease and heightened cardiovascular risk. Despite the publication of a number of recommendations regarding physical health screening in this population, monitoring rates are poor, and physical health worsened during the follow-up period.

The Metabolic Syndrome, Oxidative Stress, Environment, and Cardiovascular Disease: The Great Exploration

Science.gov (United States)

Hutcheson, Rebecca; Rocic, Petra

2012-01-01

The metabolic syndrome affects 30% of the US population with increasing prevalence. In this paper, we explore the relationship between the metabolic syndrome and the incidence and severity of cardiovascular disease in general and coronary artery disease (CAD) in particular. Furthermore, we look at the impact of metabolic syndrome on outcomes of coronary revascularization therapies including CABG, PTCA, and coronary collateral development. We also examine the association between the metabolic syndrome and its individual component pathologies and oxidative stress. Related, we explore the interaction between the main external sources of oxidative stress, cigarette smoke and air pollution, and metabolic syndrome and the effect of this interaction on CAD. We discuss the apparent lack of positive effect of antioxidants on cardiovascular outcomes in large clinical trials with emphasis on some of the limitations of these trials. Finally, we present evidence for successful use of antioxidant properties of pharmacological agents, including metformin, statins, angiotensin II type I receptor blockers (ARBs), and angiotensin II converting enzyme (ACE) inhibitors, for prevention and treatment of the cardiovascular complications of the metabolic syndrome. PMID:22829804

The Metabolic Syndrome, Oxidative Stress, Environment, and Cardiovascular Disease: The Great Exploration

Directory of Open Access Journals (Sweden)

Rebecca Hutcheson

2012-01-01

Full Text Available The metabolic syndrome affects 30% of the US population with increasing prevalence. In this paper, we explore the relationship between the metabolic syndrome and the incidence and severity of cardiovascular disease in general and coronary artery disease (CAD in particular. Furthermore, we look at the impact of metabolic syndrome on outcomes of coronary revascularization therapies including CABG, PTCA, and coronary collateral development. We also examine the association between the metabolic syndrome and its individual component pathologies and oxidative stress. Related, we explore the interaction between the main external sources of oxidative stress, cigarette smoke and air pollution, and metabolic syndrome and the effect of this interaction on CAD. We discuss the apparent lack of positive effect of antioxidants on cardiovascular outcomes in large clinical trials with emphasis on some of the limitations of these trials. Finally, we present evidence for successful use of antioxidant properties of pharmacological agents, including metformin, statins, angiotensin II type I receptor blockers (ARBs, and angiotensin II converting enzyme (ACE inhibitors, for prevention and treatment of the cardiovascular complications of the metabolic syndrome.

Microvesicles/exosomes as potential novel biomarkers of metabolic diseases

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Müller G

2012-08-01

Full Text Available Günter MüllerDepartment of Biology 1, Genetics, Ludwig-Maximilians University Munich, Biocenter, Munich, GermanyAbstract: Biomarkers are of tremendous importance for the prediction, diagnosis, and observation of the therapeutic success of common complex multifactorial metabolic diseases, such as type II diabetes and obesity. However, the predictive power of the traditional biomarkers used (eg, plasma metabolites and cytokines, body parameters is apparently not sufficient for reliable monitoring of stage-dependent pathogenesis starting with the healthy state via its initiation and development to the established disease and further progression to late clinical outcomes. Moreover, the elucidation of putative considerable differences in the underlying pathogenetic pathways (eg, related to cellular/tissue origin, epigenetic and environmental effects within the patient population and, consequently, the differentiation between individual options for disease prevention and therapy – hallmarks of personalized medicine – plays only a minor role in the traditional biomarker concept of metabolic diseases. In contrast, multidimensional and interdependent patterns of genetic, epigenetic, and phenotypic markers presumably will add a novel quality to predictive values, provided they can be followed routinely along the complete individual disease pathway with sufficient precision. These requirements may be fulfilled by small membrane vesicles, which are so-called exosomes and microvesicles (EMVs that are released via two distinct molecular mechanisms from a wide variety of tissue and blood cells into the circulation in response to normal and stress/pathogenic conditions and are equipped with a multitude of transmembrane, soluble and glycosylphosphatidylinositol-anchored proteins, mRNAs, and microRNAs. Based on the currently available data, EMVs seem to reflect the diverse functional and dysfunctional states of the releasing cells and tissues along the

Hyperferritinemia and iron metabolism in Gaucher disease: Potential pathophysiological implications.

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Regenboog, Martine; van Kuilenburg, André B P; Verheij, Joanne; Swinkels, Dorine W; Hollak, Carla E M

2016-11-01

Gaucher disease (GD) is characterized by large amounts of lipid-storing macrophages and is associated with accumulation of iron. High levels of ferritin are a hallmark of the disease. The precise mechanism underlying the changes in iron metabolism has not been elucidated. A systematic search was conducted to summarize available evidence from the literature on iron metabolism in GD and its potential pathophysiological implications. We conclude that in GD, a chronic low grade inflammation state can lead to high ferritin levels and increased hepcidin transcription with subsequent trapping of ferritin in macrophages. Extensive GD manifestations with severe anemia or extreme splenomegaly can lead to a situation of iron-overload resembling hemochromatosis. We hypothesize that specifically this latter situation carries a risk for the occurrence of associated conditions such as the increased cancer risk, metabolic syndrome and neurodegeneration. Copyright © 2016 Elsevier Ltd. All rights reserved.

Insulin Resistance in Patients with Chronic Kidney Disease

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Min-Tser Liao

2012-01-01

Full Text Available Metabolic syndrome and its components are associated with chronic kidney disease (CKD development. Insulin resistance (IR plays a central role in the metabolic syndrome and is associated with increased risk for CKD in nondiabetic patients. IR is common in patients with mild-to-moderate stage CKD, even when the glomerular filtration rate is within the normal range. IR, along with oxidative stress and inflammation, also promotes kidney disease. In patients with end stage renal disease, IR is an independent predictor of cardiovascular disease and is linked to protein energy wasting and malnutrition. Systemic inflammation, oxidative stress, elevated serum adipokines and fetuin-A, metabolic acidosis, vitamin D deficiency, depressed serum erythropoietin, endoplasmic reticulum stress, and suppressors of cytokine signaling all cause IR by suppressing insulin receptor-PI3K-Akt pathways in CKD. In addition to adequate renal replacement therapy and correction of uremia-associated factors, thiazolidinedione, ghrelin, protein restriction, and keto-acid supplementation are therapeutic options. Weight control, reduced daily prednisolone dosage, and the use of cyclosporin decrease the risk of developing new-onset diabetes after kidney transplantation. Improved understanding of the pathogenic mechanisms underlying IR in CKD may lead to more effective therapeutic strategies to reduce uremia-associated morbidity and mortality.

Mitochondrial metabolism in early neural fate and its relevance for neuronal disease modeling.

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Lorenz, Carmen; Prigione, Alessandro

2017-12-01

Modulation of energy metabolism is emerging as a key aspect associated with cell fate transition. The establishment of a correct metabolic program is particularly relevant for neural cells given their high bioenergetic requirements. Accordingly, diseases of the nervous system commonly involve mitochondrial impairment. Recent studies in animals and in neural derivatives of human pluripotent stem cells (PSCs) highlighted the importance of mitochondrial metabolism for neural fate decisions in health and disease. The mitochondria-based metabolic program of early neurogenesis suggests that PSC-derived neural stem cells (NSCs) may be used for modeling neurological disorders. Understanding how metabolic programming is orchestrated during neural commitment may provide important information for the development of therapies against conditions affecting neural functions, including aging and mitochondrial disorders. Copyright © 2017. Published by Elsevier Ltd.

Lipotoxicity in macrophages: evidence from diseases associated with the metabolic syndrome.

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Prieur, Xavier; Roszer, Tamás; Ricote, Mercedes

2010-03-01

Accumulation of lipid metabolites within non-adipose tissues can induce chronic inflammation by promoting macrophage infiltration and activation. Oxidized and glycated lipoproteins, free fatty acids, free cholesterol, triacylglycerols, diacylglycerols and ceramides have long been known to induce cellular dysfunction through their pro-inflammatory and pro-apoptotic properties. Emerging evidence suggests that macrophage activation by lipid metabolites and further modulation by lipid signaling represents a common pathogenic mechanism underlying lipotoxicity in atherosclerosis, obesity-associated insulin resistance and inflammatory diseases related to metabolic syndrome such as liver steatosis and chronic kidney disease. In this review, we discuss the latest discoveries that support the role of lipids in modulating the macrophage phenotype in different metabolic diseases. We describe the common mechanisms by which lipid derivatives, through modulation of macrophage function, promote plaque instability in the arterial wall, impair insulin responsiveness and contribute to inflammatory liver, muscle and kidney disease. We discuss the molecular mechanism of lipid activation of pro-inflammatory pathways (JNK, NFkappaB) and the key roles played by the PPAR and LXR nuclear receptors-lipid sensors that link lipid metabolism and inflammation. Copyright (c) 2009 Elsevier B.V. All rights reserved.

Hampered Vitamin B12 Metabolism in Gaucher Disease?

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Luciana Hannibal PhD

2017-02-01

Full Text Available Untreated vitamin B 12 deficiency manifests clinically with hematological abnormalities and combined degeneration of the spinal cord and polyneuropathy and biochemically with elevated homocysteine (Hcy and methylmalonic acid (MMA. Vitamin B 12 metabolism involves various cellular compartments including the lysosome, and a disruption in the lysosomal and endocytic pathways induces functional deficiency of this micronutrient. Gaucher disease (GD is characterized by dysfunctional lysosomal metabolism brought about by mutations in the enzyme beta-glucocerebrosidase (Online Mendelian Inheritance in Man (OMIM: 606463; Enzyme Commission (EC 3.2.1.45, gene: GBA1 . In this study, we collected and examined available literature on the associations between GD, the second most prevalent lysosomal storage disorder in humans, and hampered vitamin B 12 metabolism. Results from independent cohorts of patients show elevated circulating holotranscobalamin without changes in vitamin B 12 levels in serum. Gaucher disease patients under enzyme replacement therapy present normal levels of Hcy and MMA. Although within the normal range, a significant increase in Hcy and MMA with normal serum vitamin B 12 was documented in treated GD patients with polyneuropathy versus treated GD patients without polyneuropathy. Thus, a functional deficiency of vitamin B 12 caused by disrupted lysosomal metabolism in GD is a plausible mechanism, contributing to the neurological form of the disorder but this awaits confirmation. Observational studies suggest that an assessment of vitamin B 12 status prior to the initiation of enzyme replacement therapy may shed light on the role of vitamin B 12 in the pathogenesis and progression of GD.

Black leaf streak disease affects starch metabolism in banana fruit.

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Saraiva, Lorenzo de Amorim; Castelan, Florence Polegato; Shitakubo, Renata; Hassimotto, Neuza Mariko Aymoto; Purgatto, Eduardo; Chillet, Marc; Cordenunsi, Beatriz Rosana

2013-06-12

Black leaf streak disease (BLSD), also known as black sigatoka, represents the main foliar disease in Brazilian banana plantations. In addition to photosynthetic leaf area losses and yield losses, this disease causes an alteration in the pre- and postharvest behavior of the fruit. The aim of this work was to investigate the starch metabolism of fruits during fruit ripening from plants infected with BLSD by evaluating carbohydrate content (i.e., starch, soluble sugars, oligosaccharides, amylose), phenolic compound content, phytohormones, enzymatic activities (i.e., starch phosphorylases, α- and β-amylase), and starch granules. The results indicated that the starch metabolism in banana fruit ripening is affected by BLSD infection. Fruit from infested plots contained unusual amounts of soluble sugars in the green stage and smaller starch granules and showed a different pattern of superficial degradation. Enzymatic activities linked to starch degradation were also altered by the disease. Moreover, the levels of indole-acetic acid and phenolic compounds indicated an advanced fruit physiological age for fruits from infested plots.

Association between CYP2D6 Genotypes and the Risk of Antidepressant Discontinuation, Dosage Modification and the Occurrence of Maternal Depression during Pregnancy

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Anick Bérard

2017-07-01

Full Text Available Importance: Polymorphic expression of drug metabolizing enzymes affects the metabolism of antidepressants, and thus can contribute to drug response and/or adverse events. Pregnancy itself can affect CYP2D6 activity with profound variations determined by CYP2D6 genotype.Objective: To investigate the association between CYP2D6 genotype and the risk of antidepressant discontinuation, dosage modification, and the occurrence of maternal CYP2D6, Antidepressants, Depression during pregnancy.Setting: Data from the Organization of Teratology Information Specialists (OTIS Antidepressants in Pregnancy Cohort, 2006–2010, were used. Women were eligible if they were within 14 completed weeks of pregnancy at recruitment and exposed to an antidepressant or having any exposures considered non-teratogenic.Main Outcomes and Measures: Gestational antidepressant usage was self-reported and defined as continuous/discontinued use, and non-use; dosage modification was further documented. Maternal depression and anxiety were measured every trimester using the telephone interviewer-administered Edinburgh Postnatal Depression Scale and the Beck Anxiety Inventory, respectively. Saliva samples were collected and used for CYP2D6 genotype analyses. Logistic regression models were used to calculate crude and adjusted odds ratios (OR with 95% confidence intervals.Results: A total of 246 pregnant women were included in the study. The majority were normal metabolizers (NM, n = 204, 83%; 3.3% (n = 8 were ultrarapid metabolizers (UM, 5.7% (n = 14 poor metabolizers (PM, and 8.1% (n = 20 intermediate metabolizers (IM. Among study subjects, 139 women were treated with antidepressants at the beginning of pregnancy, and 21 antidepressant users (15% discontinued therapy during pregnancy. Adjusting for depressive symptoms, and other potential confounders, the risk of discontinuing antidepressants during pregnancy was nearly four times higher in slow metabolizers (poor or intermediate

Molecular Paths Linking Metabolic Diseases, Gut Microbiota Dysbiosis and Enterobacteria Infections.

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Serino, Matteo

2018-03-02

Alterations of both ecology and functions of gut microbiota are conspicuous traits of several inflammatory pathologies, notably metabolic diseases such as obesity and type 2 diabetes. Moreover, the proliferation of enterobacteria, subdominant members of the intestinal microbial ecosystem, has been shown to be favored by Western diet, the strongest inducer of both metabolic diseases and gut microbiota dysbiosis. The inner interdependence between the host and the gut microbiota is based on a plethora of molecular mechanisms by which host and intestinal microbes modify each other. Among these mechanisms are as follows: (i) the well-known metabolic impact of short chain fatty acids, produced by microbial fermentation of complex carbohydrates from plants; (ii) a mutual modulation of miRNAs expression, both on the eukaryotic (host) and prokaryotic (gut microbes) side; (iii) the production by enterobacteria of virulence factors such as the genotoxin colibactin, shown to alter the integrity of host genome and induce a senescence-like phenotype in vitro; (iv) the microbial excretion of outer-membrane vesicles, which, in addition to other functions, may act as a carrier for multiple molecules such as toxins to be delivered to target cells. In this review, I describe the major molecular mechanisms by which gut microbes exert their metabolic impact at a multi-organ level (the gut barrier being in the front line) and support the emerging triad of metabolic diseases, gut microbiota dysbiosis and enterobacteria infections. Copyright © 2018 Elsevier Ltd. All rights reserved.

Metabolic Vascular Syndrome: New Insights into a Multidimensional Network of Risk Factors and Diseases.

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Scholz, Gerhard H; Hanefeld, Markolf

2016-10-01

Since 1981, we have used the term metabolic syndrome to describe an association of a dysregulation in lipid metabolism (high triglycerides, low high-density lipoprotein cholesterol, disturbed glucose homeostasis (enhanced fasting and/or prandial glucose), gout, and hypertension), with android obesity being based on a common soil (overnutrition, reduced physical activity, sociocultural factors, and genetic predisposition). We hypothesized that main traits of the syndrome occur early and are tightly connected with hyperinsulinemia/insulin resistance, procoagulation, and cardiovascular diseases. To establish a close link between the traits of the metabolic vascular syndrome, we focused our literature search on recent original work and comprehensive reviews dealing with the topics metabolic syndrome, visceral obesity, fatty liver, fat tissue inflammation, insulin resistance, atherogenic dyslipidemia, arterial hypertension, and type 2 diabetes mellitus. Recent research supports the concept that the metabolic vascular syndrome is a multidimensional and interactive network of risk factors and diseases based on individual genetic susceptibility and epigenetic changes where metabolic dysregulation/metabolic inflexibility in different organs and vascular dysfunction are early interconnected. The metabolic vascular syndrome is not only a risk factor constellation but rather a life-long abnormality of a closely connected interactive cluster of developing diseases which escalate each other and should continuously attract the attention of every clinician.

Interlinkage among cardio-metabolic disease markers in an urban poor setting in Nairobi, Kenya

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Tilahun Nigatu Haregu

2016-02-01

Full Text Available Introduction: The main cardio-metabolic diseases – mostly cardiovascular diseases such as stroke and ischemic heart disease – share common clinical markers such as raised blood pressure and blood glucose. The pathways of development of many of these conditions are also interlinked. In this regard, a higher level of co-occurrence of the main cardio-metabolic disease markers is expected. Evidence about the patterns of occurrence of cardio-metabolic markers and their interlinkage in the sub-Saharan African setting is inadequate. Objective: The goal of the study was to describe the interlinkage among common cardio-metabolic disease markers in an African setting. Design: We used data collected in a cross-sectional study from 5,190 study participants as part of cardiovascular disease risk assessment in the urban slums of Nairobi, Kenya. Five commonly used clinical markers of cardio-metabolic conditions were considered in this analysis. These markers were waist circumference, blood pressure, random blood glucose, total blood cholesterol, and triglyceride levels. Patterns of these markers were described using means, standard deviations, and proportions. The associations between the markers were determined using odds ratios. Results: The weighted prevalence of central obesity, hypertension, hyperglycemia, hypercholesterolemia, and hypertriglyceridemia were 12.3%, 7.0%, 2.5%, 10.3%, and 17.3%, respectively. Women had a higher prevalence of central obesity and hypercholesterolemia as compared to men. Blood glucose was strongly associated with central obesity, blood pressure, and triglyceride levels, whereas the association between blood glucose and total blood cholesterol was not statistically significant. Conclusions: This study shows that most of the common cardio-metabolic markers are interlinked, suggesting a higher probability of comorbidity due to cardio-metabolic conditions and thus the need for integrated approaches.

Oxidative Stress and Metabolic Syndrome: Cause or Consequence of Alzheimer's Disease?

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Diana Luque-Contreras

2014-01-01

Full Text Available Alzheimer’s disease (AD is a major neurodegenerative disease affecting the elderly. Clinically, it is characterized by a progressive loss of memory and cognitive function. Neuropathologically, it is characterized by the presence of extracellular β-amyloid (Aβ deposited as neuritic plaques (NP and neurofibrillary tangles (NFT made of abnormal and hyperphosphorylated tau protein. These lesions are capable of generating the neuronal damage that leads to cell death and cognitive failure through the generation of reactive oxygen species (ROS. Evidence indicates the critical role of Aβ metabolism in prompting the oxidative stress observed in AD patients. However, it has also been proposed that oxidative damage precedes the onset of clinical and pathological AD symptoms, including amyloid-β deposition, neurofibrillary tangle formation, vascular malfunction, metabolic syndrome, and cognitive decline. This paper provides a brief description of the three main proteins associated with the development of the disease (Aβ, tau, and ApoE and describes their role in the generation of oxidative stress. Finally, we describe the mitochondrial alterations that are generated by Aβ and examine the relationship of vascular damage which is a potential prognostic tool of metabolic syndrome. In addition, new therapeutic approaches targeting ROS sources and metabolic support were reported.

Concordance with prescribing information dosage recommendations for dipeptidyl-peptidase-4 inhibitors among type 2 diabetes mellitus patients with moderate to severe chronic kidney disease.

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Huang, Huan; Shetty, Sharash; Bauer, Elise; Lang, Kathleen

2018-06-01

To estimate the proportion of patients with moderate to severe chronic kidney disease (CKD) whose initial dipeptidyl-peptidase-4 inhibitor (DPP4-i) dosage was concordant with prescribing information (label) recommendations in the United States. Adult patients with type 2 diabetes mellitus (T2DM) who initiated a DPP4-i (linagliptin, sitagliptin, saxagliptin) between 1 January 2011 and 30 June 2014 were identified using electronic medical records and administrative claims, with index date being the date of first observed DPP4-i treatment. Patients were required to have chronic kidney disease (CKD) stage 3b, 4 or 5 (estimated Glomerular Filtration Rate [eGFR] value <45 ml/min/1.73 m 2 ) during the 12 month pre-index period. Patients were classified as concordant or not concordant based on whether the first prescribed dose was consistent with label recommendations. Demographics, clinical characteristics, resource use and costs during pre-index were evaluated by DPP4-i concordance status. Of the 492 patients (323 sitagliptin, 57 saxagliptin, 112 linagliptin), 36.2% were prescribed doses that were not concordant with label recommendations (44.9% for sitagliptin, 57.9% for saxagliptin and 0% for linagliptin [which does not require dosage adjustment]). Concordant patients were slightly older (mean age 71 years vs. 68, p = .01) but had similar gender distribution (55% vs. 60% female, p = .31) compared to those who were not concordant. They had lower general health status (Charlson Comorbidity Score 2.6 vs. 2.2, p = .03), and had similar pre-index all-cause total costs ($25,245 vs. $21,972, p = .68) and lower pre-index T2DM-related costs ($1618 vs. $1922, p = .05). More than a third of DPP4-i patients with CKD stage 3b or higher were prescribed doses not concordant with DPP4-i label dosage recommendations.

Vascular endothelial growth factors: multitasking functionality in metabolism, health and disease.

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Smith, Gina A; Fearnley, Gareth W; Harrison, Michael A; Tomlinson, Darren C; Wheatcroft, Stephen B; Ponnambalam, Sreenivasan

2015-07-01

Vascular endothelial growth factors (VEGFs) bind to VEGF receptor tyrosine kinases (VEGFRs). The VEGF and VEGFR gene products regulate diverse regulatory pathways in mammalian development, health and disease. The interaction between a particular VEGF and its cognate VEGFR activates multiple signal transduction pathways which regulate different cellular responses including metabolism, gene expression, proliferation, migration, and survival. The family of VEGF isoforms regulate vascular physiology and promote tissue homeostasis. VEGF dysfunction is implicated in major chronic disease states including atherosclerosis, diabetes, and cancer. More recent studies implicate a strong link between response to VEGF and regulation of vascular metabolism. Understanding how this family of multitasking cytokines regulates cell and animal function has implications for treating many different diseases.

[Rehabilitation for digestive and metabolic diseases. Quo vadis?].

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Stockbrugger, R; Rosemeyer, D; Armbrecht, U

2010-10-01

The position of rehabilitation in gastroenterology, hepatology and metabolic diseases has changed little in the last 25 years. Initial improvements in quality are oriented more to the content of rehabilitative measures and less to organizational basic conditions. Nevertheless, there is an urgent need for action if rehabilitation medicine is to achieve an equivalent and recognized position in the interaction between primary care and other medical specialties. In this article suggestions for expedient prerequisites and utilization options of rehabilitation in the fields of hepatogastroenterology and metabolism will be presented, which are also oriented to the exemplary implemented concepts from Sweden and The Netherlands.

Cerebral blood flow and metabolic abnormalities in Alzheimer's disease

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Matsuda, Hiroshi

2001-01-01

In this review I summarize observations of PET and SPECT studies about cerebral blood flow and metabolic abnormalities in Alzheimer's disease (AD). In very early AD flow or metabolism reduces first in the posterior cingulate gyrus and precuneus. This reduction may arise from functional deafferentation caused by primary neural degeneration in the remote area of the entorhinal cortex that is the first to be pathologically affected in AD. Then medial temporal structures and parietotemporal association cortex show flow or metabolic reduction as disease processes. The reason why flow or metabolism in medial temporal structures shows delay in starting to reduce in spite of the earliest pathological affection remains to be elucidated. It is likely that anterior cingulate gyrus is functionally involved, since attention is the first non-memory domain to be affected, before deficits in language and visuospatial functions. However few reports have described involvement in the anterior cingulate gyrus. Relationship between cerebral blood flow or metabolism and apolipoprotein E (APOE) genotype has been investigated. Especially, the APOEε4 allele has been reported to increase risk and to lower onset age as a function of the inherited dose of the ε4 allele. Reduction of flow or metabolism in the posterior cingulate gyrus and precuneus has been reported even in presymptomatic nondemented subjects who were cognitively normal and had at least a single ε4 allele. On the contrary the relation of ε4 allele to the progression rate of AD has been controversial from neuroimaging approaches. PET and SPECT imaging has become to be quite useful for assessing therapeutical effects of newly introduced treatment for AD. Recent investigations observed significant regional flow increase after donepezil hydrochloride treatment. Most of these observations have been made by applying computer assisted analysis of three-dimensional stereotactic surface projection or statistical parametric mapping

Metabolic syndrome and risk factors for non-alcoholic fatty liver disease

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Mônica Rodrigues de Araújo Souza

2012-03-01

Full Text Available CONTEXT: Non-alcoholic fatty liver disease (NAFLD, hepatic manifestation of metabolic syndrome, has been considered the most common liver disease nowadays, which is also the most frequent cause of elevated transaminases and cryptogenic cirrhosis. The greatest input of fatty acids into the liver and consequent increased beta-oxidation contribute to the formation of free radicals, release of inflammatory cytokines and varying degrees of hepatocytic aggression, whose histological expression may vary from steatosis (HS to non-alcoholic steatohepatitis (NASH. The differentiation of these forms is required by the potential risk of progression to cirrhosis and development of hepatocellular carcinoma. OBJECTIVE: To review the literature about the major risk factors for NAFLD in the context of metabolic syndrome, focusing on underlying mechanisms and prevention. METHOD: PubMed, MEDLINE and SciELO data basis analysis was performed to identify studies describing the link between risk factors for metabolic syndrome and NAFLD. A combination of descriptors was used, non-alcoholic fatty liver disease, non-alcoholic steatohepatitis, metabolic syndrome and risk factors. At the end, 96 clinical and experimental studies, cohorts, meta-analysis and systematic reviews of great impact and scientific relevance to the topic, were selected. RESULTS: The final analysis of all these data, pointed out the central obesity, type 2 diabetes, dyslipidemia and hypertension as the best risk factors related to NAFLD. However, other factors were highlighted, such as gender differences, ethnicity, genetic factors and the role of innate immunity system. How these additional factors may be involved in the installation, progression and disease prognosis is discussed. CONCLUSION: Risk factors for NAFLD in the context of metabolic syndrome expands the prospects to 1 recognize patients with metabolic syndrome at high risk for NAFLD, 2 elucidate pathways common to other co-morbidities, 3

Progranulin: at the interface of neurodegenerative and metabolic diseases.

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Nguyen, Andrew D; Nguyen, Thi A; Martens, Lauren Herl; Mitic, Laura L; Farese, Robert V

2013-12-01

Progranulin is a widely expressed, cysteine-rich, secreted glycoprotein originally discovered for its growth factor-like properties. Its subsequent identification as a causative gene for frontotemporal dementia (FTD), a devastating early-onset neurodegenerative disease, has catalyzed a surge of new discoveries about progranulin function in the brain. More recently, progranulin was recognized as an adipokine involved in diet-induced obesity and insulin resistance, revealing its metabolic function. We review here progranulin biology in both neurodegenerative and metabolic diseases. In particular, we highlight the growth factor-like, trophic, and anti-inflammatory properties of progranulin as potential unifying themes in these seemingly divergent conditions. We also discuss potential therapeutic options for raising progranulin levels to treat progranulin-deficient FTD, as well as the possible consequences of such treatment. Copyright © 2013 Elsevier Ltd. All rights reserved.

Regional cerebral glucose metabolism in patients with Parkinson's disease with or without dementia

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Sasaki, Masayuki; Ichiya, Yuichi; Hosokawa, Shinichi; Otsuka, Makoto; Kuwabara, Yasuo; Fukumura, Toshimitsu; Kato, Motohiro; Goto, Ikuo; Masuda, Kouji [Kyushu Univ., Fukuoka (Japan). Faculty of Medicine

1992-11-01

By means of positron emission tomography, the cerebral glucose metabolism in 5 patients with Parkinson's disease with dementia was compared with that in 9 patients without dementia, and that in 5 normal volunteers. The metabolic rates for glucose were measured by placing one hundred regions of interest. In the demented patients, cerebral glucose metabolism was diffusely decreased compared with that of the non-demented patients and the normal controls. The most significant decrease in glucose metabolism was observed in the angular gyrus (49.7% of the normal controls). The glucose metabolism in the cingulate, pre- and postcentral, occipital and subcortical regions was relatively spared (62.1 to 85.5% of the normal controls). In the patients without dementia, the glucose metabolism in each region was not significantly different from that in the normal controls. These results suggest that diffuse glucose hypometabolism in the cerebral cortex may correlate with that of patients with Parkinson's disease with dementia. (author).

Obesity and Metabolic Comorbidities: Environmental Diseases?

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Carla Lubrano

2013-01-01

Full Text Available Obesity and metabolic comorbidities represent increasing health problems. Endocrine disrupting compounds (EDCs are exogenous agents that change endocrine function and cause adverse health effects. Most EDCs are synthetic chemicals; some are natural food components as phytoestrogens. People are exposed to complex mixtures of chemicals throughout their lives. EDCs impact hormone-dependent metabolic systems and brain function. Laboratory and human studies provide compelling evidence that human chemical contamination can play a role in obesity epidemic. Chemical exposures may increase the risk of obesity by altering the differentiation of adipocytes. EDCs can alter methylation patterns and normal epigenetic programming in cells. Oxidative stress may be induced by many of these chemicals, and accumulating evidence indicates that it plays important roles in the etiology of chronic diseases. The individual sensitivity to chemicals is variable, depending on environment and ability to metabolize hazardous chemicals. A number of genes, especially those representing antioxidant and detoxification pathways, have potential application as biomarkers of risk assessment. The potential health effects of combined exposures make the risk assessment process more complex compared to the assessment of single chemicals. Techniques and methods need to be further developed to fill data gaps and increase the knowledge on harmful exposure combinations.

Metabolic patterns in prion diseases: an FDG PET voxel-based analysis

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Prieto, Elena; Dominguez-Prado, Ines; Jesus Ribelles, Maria; Arbizu, Javier [Clinica Universidad de Navarra, Nuclear Medicine Department, Pamplona (Spain); Riverol, Mario; Ortega-Cubero, Sara; Rosario Luquin, Maria; Castro, Purificacion de [Clinica Universidad de Navarra, Neurology Department, Pamplona (Spain)

2015-09-15

Clinical diagnosis of human prion diseases can be challenging since symptoms are common to other disorders associated with rapidly progressive dementia. In this context, {sup 18}F-fluorodeoxyglucose (FDG) positron emission tomography (PET) might be a useful complementary tool. The aim of this study was to determine the metabolic pattern in human prion diseases, particularly sporadic Creutzfeldt-Jakob disease (sCJD), the new variant of Creutzfeldt-Jakob disease (vCJD) and fatal familial insomnia (FFI). We retrospectively studied 17 patients with a definitive, probable or possible prion disease who underwent FDG PET in our institution. Of these patients, 12 were diagnosed as sCJD (9 definitive, 2 probable and 1 possible), 1 was diagnosed as definitive vCJD and 4 were diagnosed as definitive FFI. The hypometabolic pattern of each individual and comparisons across the groups of subjects (control subjects, sCJD and FFI) were evaluated using a voxel-based analysis. The sCJD group exhibited a pattern of hypometabolism that affected both subcortical (bilateral caudate, thalamus) and cortical (frontal cortex) structures, while the FFI group only presented a slight hypometabolism in the thalamus. Individual analysis demonstrated a considerable variability of metabolic patterns among patients, with the thalamus and basal ganglia the most frequently affected areas, combined in some cases with frontal and temporal hypometabolism. Patients with a prion disease exhibit a characteristic pattern of brain metabolism presentation in FDG PET imaging. Consequently, in patients with rapidly progressive cognitive impairment, the detection of these patterns in the FDG PET study could orient the diagnosis to a prion disease. (orig.)

Metabolic patterns in prion diseases: an FDG PET voxel-based analysis

International Nuclear Information System (INIS)

Prieto, Elena; Dominguez-Prado, Ines; Jesus Ribelles, Maria; Arbizu, Javier; Riverol, Mario; Ortega-Cubero, Sara; Rosario Luquin, Maria; Castro, Purificacion de

2015-01-01

Clinical diagnosis of human prion diseases can be challenging since symptoms are common to other disorders associated with rapidly progressive dementia. In this context, 18 F-fluorodeoxyglucose (FDG) positron emission tomography (PET) might be a useful complementary tool. The aim of this study was to determine the metabolic pattern in human prion diseases, particularly sporadic Creutzfeldt-Jakob disease (sCJD), the new variant of Creutzfeldt-Jakob disease (vCJD) and fatal familial insomnia (FFI). We retrospectively studied 17 patients with a definitive, probable or possible prion disease who underwent FDG PET in our institution. Of these patients, 12 were diagnosed as sCJD (9 definitive, 2 probable and 1 possible), 1 was diagnosed as definitive vCJD and 4 were diagnosed as definitive FFI. The hypometabolic pattern of each individual and comparisons across the groups of subjects (control subjects, sCJD and FFI) were evaluated using a voxel-based analysis. The sCJD group exhibited a pattern of hypometabolism that affected both subcortical (bilateral caudate, thalamus) and cortical (frontal cortex) structures, while the FFI group only presented a slight hypometabolism in the thalamus. Individual analysis demonstrated a considerable variability of metabolic patterns among patients, with the thalamus and basal ganglia the most frequently affected areas, combined in some cases with frontal and temporal hypometabolism. Patients with a prion disease exhibit a characteristic pattern of brain metabolism presentation in FDG PET imaging. Consequently, in patients with rapidly progressive cognitive impairment, the detection of these patterns in the FDG PET study could orient the diagnosis to a prion disease. (orig.)

Association of metabolic syndrome and change in Unified Parkinson's Disease Rating Scale scores.

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Leehey, Maureen; Luo, Sheng; Sharma, Saloni; Wills, Anne-Marie A; Bainbridge, Jacquelyn L; Wong, Pei Shieen; Simon, David K; Schneider, Jay; Zhang, Yunxi; Pérez, Adriana; Dhall, Rohit; Christine, Chadwick W; Singer, Carlos; Cambi, Franca; Boyd, James T

2017-10-24

To explore the association between metabolic syndrome and the Unified Parkinson's Disease Rating Scale (UPDRS) scores and, secondarily, the Symbol Digit Modalities Test (SDMT). This is a secondary analysis of data from 1,022 of 1,741 participants of the National Institute of Neurological Disorders and Stroke Exploratory Clinical Trials in Parkinson Disease Long-Term Study 1, a randomized, placebo-controlled trial of creatine. Participants were categorized as having or not having metabolic syndrome on the basis of modified criteria from the National Cholesterol Education Program Adult Treatment Panel III. Those who had the same metabolic syndrome status at consecutive annual visits were included. The change in UPDRS and SDMT scores from randomization to 3 years was compared in participants with and without metabolic syndrome. Participants with metabolic syndrome (n = 396) compared to those without (n = 626) were older (mean [SD] 63.9 [8.1] vs 59.9 [9.4] years; p metabolic syndrome experienced an additional 0.6- (0.2) unit annual increase in total UPDRS ( p = 0.02) and 0.5- (0.2) unit increase in motor UPDRS ( p = 0.01) scores compared with participants without metabolic syndrome. There was no difference in the change in SDMT scores. Persons with Parkinson disease meeting modified criteria for metabolic syndrome experienced a greater increase in total UPDRS scores over time, mainly as a result of increases in motor scores, compared to those who did not. Further studies are needed to confirm this finding. NCT00449865. © 2017 American Academy of Neurology.

The critical role of phosphatidylcholine and phosphatidylethanolamine metabolism in health and disease.

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van der Veen, Jelske N; Kennelly, John P; Wan, Sereana; Vance, Jean E; Vance, Dennis E; Jacobs, René L

2017-09-01

Phosphatidylcholine (PC) and phosphatidylethanolamine (PE) are the most abundant phospholipids in all mammalian cell membranes. In the 1950s, Eugene Kennedy and co-workers performed groundbreaking research that established the general outline of many of the pathways of phospholipid biosynthesis. In recent years, the importance of phospholipid metabolism in regulating lipid, lipoprotein and whole-body energy metabolism has been demonstrated in numerous dietary studies and knockout animal models. The purpose of this review is to highlight the unappreciated impact of phospholipid metabolism on health and disease. Abnormally high, and abnormally low, cellular PC/PE molar ratios in various tissues can influence energy metabolism and have been linked to disease progression. For example, inhibition of hepatic PC synthesis impairs very low density lipoprotein secretion and changes in hepatic phospholipid composition have been linked to fatty liver disease and impaired liver regeneration after surgery. The relative abundance of PC and PE regulates the size and dynamics of lipid droplets. In mitochondria, changes in the PC/PE molar ratio affect energy production. We highlight data showing that changes in the PC and/or PE content of various tissues are implicated in metabolic disorders such as atherosclerosis, insulin resistance and obesity. This article is part of a Special Issue entitled: Membrane Lipid Therapy: Drugs Targeting Biomembranes edited by Pablo V. Escribá. Copyright © 2017 Elsevier B.V. All rights reserved.

Fatty Liver Index and Lipid Accumulation Product Can Predict Metabolic Syndrome in Subjects without Fatty Liver Disease

Directory of Open Access Journals (Sweden)

Yuan-Lung Cheng

2017-01-01

Full Text Available Background. Fatty liver index (FLI and lipid accumulation product (LAP are indexes originally designed to assess the risk of fatty liver and cardiovascular disease, respectively. Both indexes have been proven to be reliable markers of subsequent metabolic syndrome; however, their ability to predict metabolic syndrome in subjects without fatty liver disease has not been clarified. Methods. We enrolled consecutive subjects who received health check-up services at Taipei Veterans General Hospital from 2002 to 2009. Fatty liver disease was diagnosed by abdominal ultrasonography. The ability of the FLI and LAP to predict metabolic syndrome was assessed by analyzing the area under the receiver operating characteristic (AUROC curve. Results. Male sex was strongly associated with metabolic syndrome, and the LAP and FLI were better than other variables to predict metabolic syndrome among the 29,797 subjects. Both indexes were also better than other variables to detect metabolic syndrome in subjects without fatty liver disease (AUROC: 0.871 and 0.879, resp., and the predictive power was greater among women. Conclusion. Metabolic syndrome increases the cardiovascular disease risk. The FLI and LAP could be used to recognize the syndrome in both subjects with and without fatty liver disease who require lifestyle modifications and counseling.

Perfusion and metabolism imaging studies in Parkinson's disease

DEFF Research Database (Denmark)

Borghammer, Per

2012-01-01

Positron emission tomography (PET) and single photon emission computed tomography (SPECT) are important tools in the evaluation of brain blood flow and glucose metabolism in Parkinson's disease (PD). However, conflicting results are reported in the literature depending on the type of imaging data....... It is concluded that PD most likely is characterized by widespread cortical hypometabolism, probably even at early disease stages. Widespread subcortical hypermetabolism is probably not a feature of PD, although certain small basal ganglia structures, such as the external pallidum, may display true...

[Carbohydrate metabolism in patients with acromegaly and Itsenko-Cushing disease].

Science.gov (United States)

Matchekhina, L V; Belaya, Zh E; Melnichenko, G A; Shestakova, M V

2015-01-01

The relevance of investigating carbohydrate metabolism (CM) in patients with acromegaly and Itsenko-Cushing disease is attributable to frequent glucose metabolic disturbances, on the one hand, and to difficulties in choosing sugar-lowering therapy in these categories of patients, on the other. The efficiency of hyperglycemia treatment in these patients may be reduced due to problems in achieving remission/cure of the underlying disease and to specific therapy favoring hyperglycemia. The top-priority tasks are to search for ways of reducing the frequency of CM abnormalities in patients with neuroendocrine diseases and to elaborate sugar-lowering therapy regimens. There is a growing interest in studies of the role of the incretin system in the pathogenesis of secondary hyperglycemias associated with neuroendocrine diseases. Nevertheless, few works have been published on this subject matter because of its novelty. There is a need for a further closer study of the specific features of incretin system function and the pharmacodynamics of incretin mimetics that are potential candidates as first-line drugs to treat secondary hyperglycemias. This paper attempts to summarize the available data obtained from studies into CM in neuroendocrine diseases.

Glucose metabolism in small subcortical structures in Parkinson's disease

DEFF Research Database (Denmark)

Borghammer, Per; Hansen, Søren B; Eggers, Carsten

2012-01-01

Evidence from experimental animal models of Parkinson's disease (PD) suggests a characteristic pattern of metabolic perturbation in discrete, very small basal ganglia structures. These structures are generally too small to allow valid investigation by conventional positron emission tomography (PE...

Manipulating the circadian and sleep cycles to protect against metabolic disease

Directory of Open Access Journals (Sweden)

Kazunari eNohara

2015-03-01

Full Text Available Modernization of human society parallels an epidemic of metabolic disorders including obesity. Apart from excess caloric intake, a 24/7 lifestyle poses another important challenge to our metabolic health. Recent research under both laboratory and epidemiological settings has indicated that abnormal temporal organization of sleep and wakeful activities including food intake is a significant risk factor for metabolic disease. The circadian clock system is our intrinsic biological timer that regulates internal rhythms such as the sleep/wake cycle and also responses to external stimuli including light and food. Initially thought to be mainly involved in the timing of sleep, the clock and/or clock genes may also play a role in sleep architecture and homeostasis. Importantly, an extensive body of evidence has firmly established a master regulatory role of the clock in energy balance. Together, a close relationship between well-timed circadian/sleep cycles and metabolic health is emerging. Exploiting this functional connection, an important holistic strategy toward curbing the epidemic of metabolic disorders (e.g. obesity involves corrective measures on the circadian clock and sleep. In addition to behavioral and environmental interventions including meal timing and light control, pharmacological agents targeting sleep and circadian clocks promise convenient and effective applications. Recent studies, for example, have reported small molecules targeting specific clock components and displaying robust beneficial effects on sleep and metabolism. Furthermore, a group of clock-amplitude enhancing small molecules (CEMs identified via high-throughput chemical screens are of particular interest for future in vivo studies of their metabolic and sleep efficacies. Elucidating the functional relationship between clock, sleep and metabolism will also have far-reaching implications for various chronic human diseases and aging.

Manipulating the circadian and sleep cycles to protect against metabolic disease.

Science.gov (United States)

Nohara, Kazunari; Yoo, Seung-Hee; Chen, Zheng Jake

2015-01-01

Modernization of human society parallels an epidemic of metabolic disorders including obesity. Apart from excess caloric intake, a 24/7 lifestyle poses another important challenge to our metabolic health. Recent research under both laboratory and epidemiological settings has indicated that abnormal temporal organization of sleep and wakeful activities including food intake is a significant risk factor for metabolic disease. The circadian clock system is our intrinsic biological timer that regulates internal rhythms such as the sleep/wake cycle and also responses to external stimuli including light and food. Initially thought to be mainly involved in the timing of sleep, the clock, and/or clock genes may also play a role in sleep architecture and homeostasis. Importantly, an extensive body of evidence has firmly established a master regulatory role of the clock in energy balance. Together, a close relationship between well-timed circadian/sleep cycles and metabolic health is emerging. Exploiting this functional connection, an important holistic strategy toward curbing the epidemic of metabolic disorders (e.g., obesity) involves corrective measures on the circadian clock and sleep. In addition to behavioral and environmental interventions including meal timing and light control, pharmacological agents targeting sleep and circadian clocks promise convenient and effective applications. Recent studies, for example, have reported small molecules targeting specific clock components and displaying robust beneficial effects on sleep and metabolism. Furthermore, a group of clock-amplitude-enhancing small molecules (CEMs) identified via high-throughput chemical screens are of particular interest for future in vivo studies of their metabolic and sleep efficacies. Elucidating the functional relationship between clock, sleep, and metabolism will also have far-reaching implications for various chronic human diseases and aging.

Cardiovascular Risk Stratification in Patients with Metabolic Syndrome Without Diabetes or Cardiovascular Disease: Usefulness of Metabolic Syndrome Severity Score.

Science.gov (United States)

Masson, Walter; Epstein, Teo; Huerín, Melina; Lobo, Lorenzo Martín; Molinero, Graciela; Angel, Adriana; Masson, Gerardo; Millán, Diana; De Francesca, Salvador; Vitagliano, Laura; Cafferata, Alberto; Losada, Pablo

2017-09-01

The estimated cardiovascular risk determined by the different risk scores, could be heterogeneous in patients with metabolic syndrome without diabetes or vascular disease. This risk stratification could be improved by detecting subclinical carotid atheromatosis. To estimate the cardiovascular risk measured by different scores in patients with metabolic syndrome and analyze its association with the presence of carotid plaque. Non-diabetic patients with metabolic syndrome (Adult Treatment Panel III definition) without cardiovascular disease were enrolled. The Framingham score, the Reynolds score, the new score proposed by the 2013 ACC/AHA Guidelines and the Metabolic Syndrome Severity Calculator were calculated. Prevalence of carotid plaque was determined by ultrasound examination. A Receiver Operating Characteristic analysis was performed. A total of 238 patients were enrolled. Most patients were stratified as "low risk" by Framingham score (64%) and Reynolds score (70.1%). Using the 2013 ACC/AHA score, 45.3% of the population had a risk ≥7.5%. A significant correlation was found between classic scores but the agreement (concordance) was moderate. The correlation between classical scores and the Metabolic Syndrome Severity Calculator was poor. Overall, the prevalence of carotid plaque was 28.2%. The continuous metabolic syndrome score used in our study showed a good predictive power to detect carotid plaque (area under the curve 0.752). In this population, the calculated cardiovascular risk was heterogenic. The prevalence of carotid plaque was high. The Metabolic Syndrome Severity Calculator showed a good predictive power to detect carotid plaque.

The effect of maternal Inflammation on foetal programming of metabolic disease

DEFF Research Database (Denmark)

Ingvorsen, Camilla; Pedersen, Susanne Brix; Ozanne, S. E.

2015-01-01

‐grade inflammatory diseases, such as rheumatoid arthritis, that pregnancy can improve disease state. If pregnancy is also capable of suppressing the obesity‐associated inflammation, the immunological markers might be less likely to affect metabolic programming in the developing foetus than otherwise implied....

Role of innate lymphoid cells in obesity and metabolic disease

Science.gov (United States)

Saetang, Jirakrit; Sangkhathat, Surasak

2018-01-01

The immune system has previously been demonstrated to be associated with the pathophysiological development of metabolic abnormalities. However, the mechanisms linking immunity to metabolic disease remain to be fully elucidated. It has previously been suggested that innate lymphoid cells (ILCs) may be involved in the progression of numerous types of metabolic diseases as these cells act as suppressors and promoters for obesity and associated conditions, and are particularly involved in adipose tissue inflammation, which is a major feature of metabolic imbalance. Group 2 ILCs (ILC2s) have been revealed as anti-obese immune regulators by secreting anti-inflammatory cytokines and promoting the polarization of M2 macrophages, whereas group 1 ILCs (ILC1s), including natural killer cells, may promote adipose tissue inflammation via production of interferon-γ, which in turn polarizes macrophages toward the M1 type. The majority of studies to date have demonstrated the pathological association between ILCs and obesity in the context of adipose tissue inflammation, whereas the roles of ILCs in other organs which participate in obesity development have not been fully characterized. Therefore, identifying the roles of all types of ILCs as central components mediating obesity-associated inflammation, is of primary concern, and may lead to the discovery of novel preventative and therapeutic interventions. PMID:29138853

Metabolic adaptations in models of fatty liver disease : Of mice and math

NARCIS (Netherlands)

Hijmans, Brenda

2017-01-01

The increasing incidence of overweight is accompanied by a plethora of medical symptoms together called the metabolic syndrome. Non-alcoholic fatty liver disease, characterized by persistent storage of lipids in the liver, is regarded as the hepatic component of the metabolic syndrome. An imbalance

Metabolic differentiation of early Lyme disease from southern tick-associated rash illness (STARI).

Science.gov (United States)

Molins, Claudia R; Ashton, Laura V; Wormser, Gary P; Andre, Barbara G; Hess, Ann M; Delorey, Mark J; Pilgard, Mark A; Johnson, Barbara J; Webb, Kristofor; Islam, M Nurul; Pegalajar-Jurado, Adoracion; Molla, Irida; Jewett, Mollie W; Belisle, John T

2017-08-16

Lyme disease, the most commonly reported vector-borne disease in the United States, results from infection with Borrelia burgdorferi. Early clinical diagnosis of this disease is largely based on the presence of an erythematous skin lesion for individuals in high-risk regions. This, however, can be confused with other illnesses including southern tick-associated rash illness (STARI), an illness that lacks a defined etiological agent or laboratory diagnostic test, and is coprevalent with Lyme disease in portions of the eastern United States. By applying an unbiased metabolomics approach with sera retrospectively obtained from well-characterized patients, we defined biochemical and diagnostic differences between early Lyme disease and STARI. Specifically, a metabolic biosignature consisting of 261 molecular features (MFs) revealed that altered N -acyl ethanolamine and primary fatty acid amide metabolism discriminated early Lyme disease from STARI. Development of classification models with the 261-MF biosignature and testing against validation samples differentiated early Lyme disease from STARI with an accuracy of 85 to 98%. These findings revealed metabolic dissimilarity between early Lyme disease and STARI, and provide a powerful and new approach to inform patient management by objectively distinguishing early Lyme disease from an illness with nearly identical symptoms. Copyright © 2017 The Authors, some rights reserved; exclusive licensee American Association for the Advancement of Science. No claim to original U.S. Government Works.

The 2009 stock conference report: inflammation, obesity and metabolic disease.

Science.gov (United States)

Hevener, A L; Febbraio, M A

2010-09-01

Obesity is linked with many deleterious health consequences and is associated with increased risk of chronic disease including type 2 diabetes, atherosclerosis and certain forms of cancer. Recent work has highlighted the impact of obesity to activate inflammatory gene networks and suggests a causal function of inflammation in the pathogenesis of the metabolic syndrome. Since 2005, when Dr Gokhan Hotamisligil chaired the fourth Stock Conference in Istanbul, Turkey, entitled 'Obesity and Inflammation', there has been an explosion of studies investigating the relationship between obesity, inflammation and substrate metabolism. The exuberance surrounding this field of research is exemplified by the body of work that has been published in these past 4 years, including over 1400 publications. During this time, several novel mechanisms relating to cellular inflammation have been uncovered including the role of the hematopoietic system, toll-like receptor activation, endoplasmic reticulum stress and very recently T-cell activation in obesity-induced insulin resistance. These discoveries have led us to rethink cellular nutrient sensing and its role in inflammation and metabolic disease. Despite burgeoning investigation in this field, there still remain a number of unanswered questions. This review that evolved from the 2009 Stock Conference summarizes current research and identifies the deficiencies in our understanding of this topic. The overall goal of this Stock Conference was to bring together leading investigators in the field of inflammation and obesity research in the hope of fostering new ideas, thus advancing the pursuit of novel therapeutic strategies to reduce disease risk and or better treat chronic disease including type 2 diabetes, cardiovascular disease and cancer. © 2009 The Authors. obesity reviews © 2009 International Association for the Study of Obesity.

[Endocrinological diseases, metabolic diseases, sexuality].

Science.gov (United States)

Lemaire, Antoine

2014-10-01

Sexuality is regularly evaluated in media surveys. Relations between sexual problems and some chronic pathologies as diabetes or metabolic syndrome have been brought to light. Androgen deficiency in the aging male has become a topic of increasing interest. Hormones play an important role in sexual function and relation between hormonal status and metabolic data are now well established. Copyright © 2014. Published by Elsevier Masson SAS.

Hematopoietic Gene Therapies for Metabolic and Neurologic Diseases.

Science.gov (United States)

Biffi, Alessandra

2017-10-01

Increasingly, patients affected by metabolic diseases affecting the central nervous system and neuroinflammatory disorders receive hematopoietic cell transplantation (HCT) in the attempt to slow the course of their disease, delay or attenuate symptoms, and improve pathologic findings. The possible replacement of brain-resident myeloid cells by the transplanted cell progeny contributes to clinical benefit. Genetic engineering of the cells to be transplanted (hematopoietic stem cell) may endow the brain myeloid progeny of these cells with enhanced or novel functions, contributing to therapeutic effects. Copyright © 2017 Elsevier Inc. All rights reserved.

Systems biology from micro-organisms to human metabolic diseases: the role of detailed kinetic models.

Science.gov (United States)

Bakker, Barbara M; van Eunen, Karen; Jeneson, Jeroen A L; van Riel, Natal A W; Bruggeman, Frank J; Teusink, Bas

2010-10-01

Human metabolic diseases are typically network diseases. This holds not only for multifactorial diseases, such as metabolic syndrome or Type 2 diabetes, but even when a single gene defect is the primary cause, where the adaptive response of the entire network determines the severity of disease. The latter may differ between individuals carrying the same mutation. Understanding the adaptive responses of human metabolism naturally requires a systems biology approach. Modelling of metabolic pathways in micro-organisms and some mammalian tissues has yielded many insights, qualitative as well as quantitative, into their control and regulation. Yet, even for a well-known pathway such as glycolysis, precise predictions of metabolite dynamics from experimentally determined enzyme kinetics have been only moderately successful. In the present review, we compare kinetic models of glycolysis in three cell types (African trypanosomes, yeast and skeletal muscle), evaluate their predictive power and identify limitations in our understanding. Although each of these models has its own merits and shortcomings, they also share common features. For example, in each case independently measured enzyme kinetic parameters were used as input. Based on these 'lessons from glycolysis', we will discuss how to make best use of kinetic computer models to advance our understanding of human metabolic diseases.

Metabolic epidermal necrosis in two dogs with different underlying diseases.

Science.gov (United States)

Bond, R; McNeil, P E; Evans, H; Srebernik, N

1995-05-06

Two dogs with metabolic epidermal necrosis had hyperkeratosis of the footpads accompanied by erythematous, erosive and crusting lesions affecting the muzzle, external genitalia, perineum and periocular regions. Histopathological examination of skin biopsies revealed a superficial hydropic dermatitis with marked parakeratosis. Both dogs had high plasma activities of alkaline phosphatase and alanine aminotransferase and high concentrations of glucose, and also a marked hypoaminoacidaemia. Despite these similarities, the cutaneous eruptions were associated with different underlying diseases. One dog had a pancreatic carcinoma which had metastasised widely; the primary tumour and the metastases showed glucagon immunoreactivity on immunocytochemical staining, and the dog's plasma glucagon concentration was markedly greater than that of control dogs. The other dog had diffuse hepatic disease; its plasma glucagon concentration was similar to that of control samples and cirrhosis was identified post mortem. Metabolic epidermal necrosis in dogs is a distinct cutaneous reaction pattern which may be associated with different underlying systemic diseases; however, the pathogenesis of the skin lesions remains unclear.

General Requirements to the Preparation of Tinctures, Decoctions. Dosage of Phytopreparations

Directory of Open Access Journals (Sweden)

I.B. Yershovа

2016-09-01

Full Text Available The article describes the advantages and disadvantages of using herbal medicine, general information for the collection of medicinal plants. According to the World Health Organization, the classification of herbal medicine is an integral part of traditional medicine. It refers to the variety of metabolic therapy. This treatment meets the requirements of pathogenetic therapy. Currently, more than 30 % of medicines on the pharmaceutical market have herbal origin. According to the World Health Organization, about 80 % of the world population use mainly traditional medicines of natural origin within the framework of primary health care system. Analysis of publications on phytotherapy revealed insufficient coverage of contraindications and side effects of certain plants. This was the basis for opening in our magazine this column, and we wanted to start with what would be the advantages and disadvantages of phytotherapy. Benefits of herbal medi­cine: biological proximity of the active substances of plants and active substances of the body, harmony therapy for the human body, the prolonged effect of herbal medicines after the completion of therapy, the opportunity to prepare a wide variety of different dosage forms, for both indoor and outdoor use, compatibility with many synthetic pharmaceuticals drugs, comprehensive multilateral action of plants, no side effects, simplicity and ease of preparation of herbal remedies at home, the availability for the majority of patients due to the low cost of the medicines. Limitations of herbal medicine: the complexity of the standardization of the treatment effect of herbal drugs, the complexity of establishing a dose, selectivity of diseases, in which typical herbal remedies are prescribed, the risk of poisoning, particularly in self-collection of medicinal plants. The article also provides methods for the preparation of various forms of herbal remedies, dosage for adults and children. With all the advantages of

Cyclic vomiting syndrome masking a fatal metabolic disease.

LENUS (Irish Health Repository)

Fitzgerald, Marianne

2013-05-01

Disorders of fatty acid oxidation are rare but can be fatal. Hypoglycaemia with acidosis is a cardinal feature. Cases may present during early childhood or can be delayed into adolescence or beyond. We present a case of multiple acyl-coenzyme A dehydrogenase deficiency (MADD), an extremely rare disorder of fatty acid oxidation. Our 20-year-old patient presented with cardiovascular collapse, raised anion gap metabolic acidosis and non-ketotic hypoglycaemia. She subsequently developed multi-organ failure and sadly died. She had a previous diagnosis of cyclic vomiting syndrome (CVS) for more than 10 years, warranting frequent hospital admissions. The association between CVS and MADD has been made before though the exact relationship is unclear. All patients with persistent severe CVS should have metabolic investigations to exclude disorders of fatty acid oxidation. In case of non-ketotic hypoglycaemia with acidosis, the patient should be urgently referred to a specialist in metabolic diseases. All practitioners should be aware of these rare disorders as a cause of unexplained acidosis.

Methotrexate Dosage Reduction Upon Adalimumab Initiation: Clinical and Ultrasonographic Outcomes from the Randomized Noninferiority MUSICA Trial.

Science.gov (United States)

Kaeley, Gurjit S; Evangelisto, Amy M; Nishio, Midori J; Goss, Sandra L; Liu, Shufang; Kalabic, Jasmina; Kupper, Hartmut

2016-08-01

To examine the clinical and ultrasonographic (US) outcomes of reducing methotrexate (MTX) dosage upon initiating adalimumab (ADA) in MTX-inadequate responders with moderately to severely active rheumatoid arthritis (RA). MUSICA (NCT01185288) was a double-blind, randomized, parallel-arm study of 309 patients with RA receiving MTX ≥ 15 mg/week for ≥ 12 weeks before screening. Patients were randomized to high dosage (20 mg/week) or low dosage (7.5 mg/week) MTX; all patients received 40 mg open-label ADA every other week for 24 weeks. The primary endpoint was Week 24 mean 28-joint Disease Activity Score based on C-reactive protein (DAS28-CRP) to test for noninferiority of low-dosage MTX using a 15% margin. US images were scored using a 10-joint semiquantitative system incorporating OMERACT definitions for pathology, assessing synovial hypertrophy, vascularity, and bony erosions. Rapid improvement in clinical indices was observed in both groups after addition of ADA. The difference in mean DAS28-CRP (0.37, 95% CI 0.07-0.66) comparing low-dosage (4.12, 95% CI 3.88-4.34) versus high-dosage MTX (3.75, 95% CI 3.52-3.97) was statistically significant and non-inferiority was not met. Statistically significant differences were not detected for most clinical, functional, and US outcomes. Pharmacokinetic and safety profiles were similar. In MUSICA, Week 24 mean DAS28-CRP, the primary endpoint, did not meet non-inferiority for the low-dosage MTX group. Although the differences between the 2 MTX dosage groups were small, our study findings did not support routine MTX reduction in MTX inadequate responders initiating ADA.

Metabolomic applications to decipher gut microbial metabolic influence in health and disease

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Francois-Pierre eMartin

2012-04-01

Full Text Available Dietary preferences and nutrients composition have been shown to influence human and gut microbial metabolism, which ultimately has specific effects on health and diseases’ risk. Increasingly, results from molecular biology and microbiology demonstrate the key role of the gut microbiota metabolic interface to the overall mammalian host’s health status. There is therefore raising interest in nutrition research to characterize the molecular foundations of the gut microbial mammalian cross-talk at both physiological and biochemical pathway levels. Tackling these challenges can be achieved through systems biology approaches, such as metabolomics, to underpin the highly complex metabolic exchanges between diverse biological compartments, including organs, systemic biofluids and microbial symbionts. By the development of specific biomarkers for prediction of health and disease, metabolomics is increasingly used in clinical applications as regard to disease aetiology, diagnostic stratification and potentially mechanism of action of therapeutical and nutraceutical solutions. Surprisingly, an increasing number of metabolomics investigations in pre-clinical and clinical studies based on proton nuclear magnetic resonance (1H NMR spectroscopy and mass spectrometry (MS provided compelling evidence that system wide and organ-specific biochemical processes are under the influence of gut microbial metabolism. This review aims at describing recent applications of metabolomics in clinical fields where main objective is to discern the biochemical mechanisms under the influence of the gut microbiota, with insight into gastrointestinal health and diseases diagnostics and improvement of homeostasis metabolic regulation.

Hexarelin Signaling to PPARγ in Metabolic Diseases

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Amélie Rodrigue-Way

2008-01-01

Full Text Available Investigating the metabolic functions of the nuclear receptor peroxisome proliferator-activated receptor γ (PPARγ has been extremely rewarding over the past years. Uncovering the biologic roles of PPARγ and its mechanism of action has greatly advanced our understanding of the transcriptional control of lipid and glucose metabolism, and compounds such as thiazolidinediones which directly regulate PPARγ have proven to exhibit potent insulin-sensitizer effects in the treatment of diabetes. We review here recent advances on the emerging role of growth hormone releasing peptides in regulating PPARγ through interaction with scavenger receptor CD36 and ghrelin GHS-R1a receptor. With the impact that these peptides exert on the metabolic pathways involved in lipid metabolism and energy homeostasis, it is hoped that the development of novel approaches in the regulation of PPAR functions will bring additional therapeutic possibilities to face problems related to metabolic diseases.

UCB Transplant of Inherited Metabolic Diseases With Administration of Intrathecal UCB Derived Oligodendrocyte-Like Cells

Science.gov (United States)

2018-03-15

Adrenoleukodystrophy; Batten Disease; Mucopolysaccharidosis II; Leukodystrophy, Globoid Cell; Leukodystrophy, Metachromatic; Neimann Pick Disease; Pelizaeus-Merzbacher Disease; Sandhoff Disease; Tay-Sachs Disease; Brain Diseases, Metabolic, Inborn; Alpha-Mannosidosis; Sanfilippo Mucopolysaccharidoses

Development of a Novel Targeted RNAi Delivery Technology inTherapies for Metabolic Diseases

Science.gov (United States)

2017-10-01

report Impact on other disciplines: Nothing to report Impact on technology transfer: Nothing to report Impact on society : Nothing to report 5. CHANGES...AWARD NUMBER: W81XWH-15-1-0569 TITLE: Development of a Novel Targeted RNAi Delivery Technology in Therapies for Metabolic Diseases PRINCIPAL...COVERED 30Sep2016 - 29Sep2017 4. TITLE AND SUBTITLE Development of a Novel Targeted RNAi Delivery Technology in Therapies for Metabolic Diseases 5a

Features of Mineral Metabolism and Parathyroid Glands Functioning in Chronic Renal Disease

Directory of Open Access Journals (Sweden)

L.P. Martynyuk

2012-04-01

Full Text Available The calcium phosphoric metabolism was analyzed depending on the severity of renal functioning disorders. Chronic renal disease is known to be associated with impaired mineral metabolism in terms of hypocalcaemia, hyperphosphatemia and enhanced level of Ca × P product that aggravates in chronic renal failure progression. The majority of patients with nephropathy have parathyroid hormone concentration to be different from target one recommended by NKF-K/DOQI (2003, at that secondary hyperparathyroidism prevails on pre-dialysis stage of chronic renal disease, the relative hypoparathyroidism is common among the patients received dialysis.

Cerebral Metabolic Differences Associated with Cognitive Impairment in Parkinson's Disease.

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Yilin Tang

Full Text Available To characterize cerebral glucose metabolism associated with different cognitive states in Parkinson's disease (PD using 18F-fluorodeoxyglucose (FDG and Positron Emission Tomography (PET.Three groups of patients were recruited in this study including PD patients with dementia (PDD; n = 10, with mild cognitive impairment (PD-MCI; n = 20, and with no cognitive impairment (PD-NC; n = 30. The groups were matched for age, sex, education, disease duration, motor disability, levodopa equivalent dose and Geriatric Depression Rating Scale (GDS score. All subjects underwent a FDG-PET study. Maps of regional metabolism in the three groups were compared using statistical parametric mapping (SPM5.PD-MCI patients exhibited limited areas of hypometabolism in the frontal, temporal and parahippocampal gyrus compared with the PD-NC patients (p < 0.01. PDD patients had bilateral areas of hypometabolism in the frontal and posterior parietal-occipital lobes compared with PD-MCI patients (p < 0.01, and exhibited greater metabolic reductions in comparison with PD-NC patients (p < 0.01.Compared with PD-NC patients, hypometabolism was much higher in the PDD patients than in PD-MCI patients, mainly in the posterior cortical areas. The result might suggest an association between posterior cortical hypometabolism and more severe cognitive impairment. PD-MCI might be important for early targeted therapeutic intervention and disease modification.

Lactate metabolism in chronic liver disease

DEFF Research Database (Denmark)

Jeppesen, Johanne B; Mortensen, Christian; Bendtsen, Flemming

2013-01-01

Background. In the healthy liver there is a splanchnic net-uptake of lactate caused by gluconeogenesis. It has previously been shown that patients with acute liver failure in contrast have a splanchnic release of lactate caused by a combination of accelerated glycolysis in the splanchnic region...... and a reduction in hepatic gluconeogenesis. Aims. The aims of the present study were to investigate lactate metabolism and kinetics in patients with chronic liver disease compared with a control group with normal liver function. Methods. A total of 142 patients with chronic liver disease and 14 healthy controls...... underwent a liver vein catheterization. Blood samples from the femoral artery and the hepatic and renal veins were simultaneously collected before and after stimulation with galactose. Results. The fasting lactate levels, both in the hepatic vein and in the femoral artery, were higher in the patients than...

Diminished neuronal metabolic activity in Alzheimer's disease. Review article

NARCIS (Netherlands)

Salehi, A.; Swaab, D. F.

1999-01-01

An increasing number of studies have appeared in the literature suggesting that Alzheimer's disease (AD) is a hypometabolic brain disorder. Decreased metabolism in AD has been revealed by a variety of in vivo and postmortem methods and techniques including positron emission tomography and glucose

Detection of metabolic syndrome features among childhood cancer survivors: A target to prevent disease

Directory of Open Access Journals (Sweden)

Adriana Aparecida Siviero-Miachon

2008-08-01

Full Text Available Adriana Aparecida Siviero-Miachon1, Angela Maria Spinola-Castro1, Gil Guerra-Junior21Division of Pediatric Endocrinology, Department of Pediatrics, Federal University of Sao Paulo – UNIFESP/EPM, Brazil; 2Division of Pediatric Endocrinology, Department of Pediatrics, State University of Campinas – FCM/UNICAMP, BrazilAbstract: Along with the growing epidemic of obesity, the risk of atherosclerosis, cardiovascular disease morbidity, and mortality are increasing markedly. Several risk factors for cardiovascular disease, such as visceral obesity, glucose intolerance, arterial hypertension, and dyslipidemia commonly cluster together as a condition currently known as metabolic syndrome. Thus far, insulin resistance, and endothelial dysfunction are the primary events of the metabolic syndrome. Several groups have recommended clinical criteria for the diagnosis of metabolic syndrome in adults. Nonetheless, in what concerns children and adolescents, there are no unified definitions, and modified adult criteria have been suggested by many authors, despite major problems. Some pediatric disease states are at risk for premature cardiovascular disease, with clinical coronary events occurring very early in adult life. Survivors of specific pediatric cancer groups, particularly acute lymphocytic leukemia, central nervous system tumors, sarcomas, lymphomas, testicular cancer, and following bone marrow transplantation, may develop metabolic syndrome traits due to: hormonal deficiencies (growth hormone deficiency, thyroid dysfunction, and gonadal failure, drug or radiotherapy damage, endothelial impairment, physical inactivity, adipose tissue dysfunction, and/or drug-induced magnesium deficiency. In conclusion, some primary and secondary prevention remarks are proposed in order to reduce premature cardiovascular disease risk in this particular group of patients.Keywords: metabolic syndrome X, cardiovascular diseases, insulin resistance, obesity, growth hormone

[Pharmaceutical advice concerning different pharmaceutical dosage forms].

Science.gov (United States)

Szakonyi, Gergely; Zelkó, Romána

2010-01-01

The present paper summarizes the commonly applied types of drug uptake and the pharmacists' advice concerning a certain dosage form. The manuscript also deals with the modified release dosage forms and their abbreviations in the name of the marketing authorized products.

Use of radiation and radioisotopes for investigating metabolic diseases of animals in India

Energy Technology Data Exchange (ETDEWEB)

Arora, S P [National Dairy Research Inst., Karnal (India). Div. of Dairy Cattle Nutrition and Physiology

1980-03-01

In the last decade, radioisotopes have been used to investigate certain metabolic diseases of animals and radiation is being utilized to produce parasitic vaccines to vaccinate animals. Some studies in which radioisotopes have been used to investigate certain metabolic disorders are reviewed. In experiments where radioimmunoassay technique for the estimation of hormones, has been utilized, the results reveal that the animals on low level of nutrition show greater oestrous cycle lengths or even long anoestrous periods. On the other hand, irradiation has been used as a tool to produce vaccines as well as degradation of certain dietary molecules for increased utilization. A number of studies wherein /sup 35/S and /sup 15/N isotopes have been used, reveal that sulphur supplementation is essential for optimum utilization of nitrogen in the ratio of 1:10. There are certain antimetabolites in feed ingredients which affect endocrine function. Evidence indicates that high nitrate forages disturb thyroid function when sup(131)I is used to elucidate its secretion rate. Similarly certain toxic substances such as tannins have been shown to affect protein metabolism and phosphorus utilization when sup(32)P isotope is used in such studies. The use of radioisotopes has also been helpful to investigate the cause of ''Degnala'' disease prevalent in village cattle in certain states of India. With the help of sup(75)Se it has been possible to trace the metabolic disturbances which lead to the onset of this disease. Another deficiency disease, hyperkeratosis, has been shown to be caused not only because of vitamin A deficiency, but also because of zinc deficiency. The latter helps in the mobilization of a normal quantity of vitamin A from the liver into the blood vitamin A pool. There is wide scope for use of radioisotopes to investigate other metabolic diseases prevalent in livestock in this country.

Use of radiation and radioisotopes for investigating metabolic diseases of animals in India

International Nuclear Information System (INIS)

Arora, S.P.

1980-01-01

In the last one decade, radioisotopes are being used to investigate certain metabolic diseases of animals and radiations are being utilized to produce parasitic vaccines to vaccinate animals. Some studies in which radioisotopes have been used to investigate certain metabolic disorders are reviewed. In experiments, where radioimmunoassay technique for the estimation of hormones, has been utilized, the results reveal that the animals on low plane of nutrition show greater oestrous cycle lengths or even long anoestrous periods. On the other hand, irradiation has been used as a tool to produce vaccines as well as degradation of certain dietary molecules for increased utilization. A number of studies wherein 35 S and 15 N isotopes have been used, reveal that sulphur supplementation is essential for optimum utilization of nitrogen in the ratio of 1:10. There are certain antimetabolites in feed ingredients which affect endocrine function. Evidence indicates that high nitrate forages disturb thyroid function when sup(131)I is used to elucidate its secretion rate. Similarly certain toxic substances such as tannins have been shown to affect protein metabolism and phosphorus utilization when sup(32)P isotope is used in such studies. The use of radioisotopes have also been helpful to investigate the cause of ''Degnala'' disease prevalent in village cattle in certain states of India. With the help of sup(75)Se it has been possible to trace out the metabolic disturbances which lead to the onset of this disease. Another deficiency disease, hyperkeratosis, has been shown to be caused not only because of Vitamin A deficiency, but also because of zinc deficiency. The latter helps in the mobilization of normal quantity of vitamin A from the liver into the blood vitamin A pool. There is wide scope to use radioisotopes to investigate other metabolic diseases prevalent in livestock in this country. (auth.)

Chewing betel quid and the risk of metabolic disease, cardiovascular disease, and all-cause mortality: a meta-analysis.

Science.gov (United States)

Yamada, Tomohide; Hara, Kazuo; Kadowaki, Takashi

2013-01-01

Betel nut (Areca nut) is the fruit of the Areca catechu tree. Approximately 700 million individuals regularly chew betel nut (or betel quid) worldwide and it is a known risk factor for oral cancer and esophageal cancer. We performed a meta-analysis to assess the influence of chewing betel quid on metabolic diseases, cardiovascular disease, and all-cause mortality. We searched Medline, Cochrane Library, Web of Science, and Science Direct for pertinent articles (including the references) published between 1951 and 2013. The adjusted relative risk (RR) and 95% confidence interval were calculated using the random effect model. Sex was used as an independent category for comparison. Of 580 potentially relevant studies, 17 studies from Asia (5 cohort studies and 12 case-control studies) covering 388,134 subjects (range: 94 to 97,244) were selected. Seven studies (N = 121,585) showed significant dose-response relationships between betel quid consumption and the risk of events. According to pooled analysis, the adjusted RR of betel quid chewers vs. non-chewers was 1.47 (PBetel quid chewing is associated with an increased risk of metabolic disease, cardiovascular disease, and all-cause mortality. Thus, in addition to preventing oral cancer, stopping betel quid use could be a valuable public health measure for metabolic diseases that are showing a rapid increase in South-East Asia and the Western Pacific.

NMR as a probe metabolic disorders in disease and treatment

Energy Technology Data Exchange (ETDEWEB)

Yushmanov, Victor E [Russian Academy of Sciences, Moscow (Russian Federation). Inst. of Chemical Physics

1994-12-31

The effects of malignant tumors, chemical and physical factors (toxic agents, ionizing radiation) as well as of their treatment on tissue metabolism were studied by NMR imaging. The importance of NMR is highlighted since it enables to a better understanding of molecular mechanisms of diseases and therapeutic interventions, in addition to the analysis of metabolic disorders in human beings. Combined with the studies of experimental animal pathologies, may constitute a base for new types of NMR-diagnosis in vivo 10 refs.

Determining S-1 dosage at hospitals prioritizing cancer chemotherapy

International Nuclear Information System (INIS)

Morimoto, Shigefumi; Kitada, Noriaki; Anami, Setsuko

2008-01-01

Although it is recommended that the standard S-1 dosage should be based on how large the body surface area is, an on-site setting of the appropriate dosage is often lower than the standard one, depending on the individual's condition and considering possible side effects and so, on. Here, we investigated usage conditions for S-1 as a part of field training for expert pharmacists at our hospital that performs total clinical treatments. Decreases in dosage per day for elderly patients were although the standard dosage is generally determined according to the amount of a patient's body surface. We conducted a retrospective survey with a total 90 patients by creating a tree-diagram to identify a reduction standard. It was found that the S-1 dosage was decreased when there were side effects, aggravation in performance status, decrease in kidney function, old age, combined injection chemotherapy, and a decrease in radiation therapy performance. The dosage decreases without such medical reasons were seen in only 4 of the 90 patients. At hospitals giving priority to chemotherapy, it became clear that appropriate treatment was promoted by decreasing. The individual target dosage on the basis of daily medical examination. (author)

Intelligent system for improving dosage control

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Fabio Cosme Rodrigues dos Santos

2017-02-01

Full Text Available Coagulation is one of the most important processes in a drinking-water treatment plant, and it is applied to destabilize impurities in water for the subsequent flocculation stage. Several techniques are currently used in the water industry to determine the best dosage of the coagulant, such as the jar-test method, zeta potential measurements, artificial intelligence methods, comprising neural networks, fuzzy and expert systems, and the combination of the above-mentioned techniques to help operators and engineers in the water treatment process. Current paper presents an artificial neural network approach to evaluate optimum coagulant dosage for various scenarios in raw water quality, using parameters such as raw water color, raw water turbidity, clarified and filtered water turbidity and a calculated Dose Rate to provide the best performance in the filtration process. Another feature in current approach is the use of a backpropagation neural network method to estimate the best coagulant dosage simultaneously at two points of the water treatment plant. Simulation results were compared to the current dosage rate and showed that the proposed system may reduce costs of raw material in water treatment plant.

Synthetic dosage lethality in the human metabolic network is highly predictive of tumor growth and cancer patient survival.

Science.gov (United States)

Megchelenbrink, Wout; Katzir, Rotem; Lu, Xiaowen; Ruppin, Eytan; Notebaart, Richard A

2015-09-29

Synthetic dosage lethality (SDL) denotes a genetic interaction between two genes whereby the underexpression of gene A combined with the overexpression of gene B is lethal. SDLs offer a promising way to kill cancer cells by inhibiting the activity of SDL partners of activated oncogenes in tumors, which are often difficult to target directly. As experimental genome-wide SDL screens are still scarce, here we introduce a network-level computational modeling framework that quantitatively predicts human SDLs in metabolism. For each enzyme pair (A, B) we systematically knock out the flux through A combined with a stepwise flux increase through B and search for pairs that reduce cellular growth more than when either enzyme is perturbed individually. The predictive signal of the emerging network of 12,000 SDLs is demonstrated in five different ways. (i) It can be successfully used to predict gene essentiality in shRNA cancer cell line screens. Moving to clinical tumors, we show that (ii) SDLs are significantly underrepresented in tumors. Furthermore, breast cancer tumors with SDLs active (iii) have smaller sizes and (iv) result in increased patient survival, indicating that activation of SDLs increases cancer vulnerability. Finally, (v) patient survival improves when multiple SDLs are present, pointing to a cumulative effect. This study lays the basis for quantitative identification of cancer SDLs in a model-based mechanistic manner. The approach presented can be used to identify SDLs in species and cell types in which "omics" data necessary for data-driven identification are missing.

Respiratory alkalosis and metabolic acidosis in a child treated with sulthiame.

Science.gov (United States)

Weissbach, Avichai; Tirosh, Irit; Scheuerman, Oded; Hoffer, Vered; Garty, Ben Zion

2010-10-01

To report on severe acid-base disturbance in a child with symptomatic epilepsy treated with sulthiame. A 9.5-year-old boy with chronic generalized tonic-clonic seizures was treated with carbamazepine and valproic acid. Because of poor seizure control, sulthiame was added to the treatment. Two months later, he presented at the emergency department with severe weakness, headache, dizziness, dyspnea, anorexia, and confusional state. Arterial blood gas analysis showed mixed respiratory alkalosis with high anion gap metabolic acidosis. Sulthiame-induced acid-base disturbance was suspected. The drug was withheld for the first 24 hours and then restarted at a reduced dosage. The arterial blood gases gradually normalized, the confusion disappeared, and the patient was discharged home.Three months later, 4 weeks after an increase in sulthiame dosage, the patient was once again admitted with the same clinical picture. Improvement was noted after the drug dosage was reduced. This is the first report of mixed respiratory alkalosis and metabolic acidosis in a child treated with sulthiame. Monitoring of the acid-base status should be considered in patients treated with sulthiame.

parkin mutation dosage and the phenomenon of anticipation: a molecular genetic study of familial parkinsonism

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Schellenberg Gerard D

2005-02-01

Full Text Available Abstract Background parkin mutations are a common cause of parkinsonism. Possessing two parkin mutations leads to early-onset parkinsonism, while having one mutation may predispose to late-onset disease. This dosage pattern suggests that some parkin families should exhibit intergenerational variation in age at onset resembling anticipation. A subset of familial PD exhibits anticipation, the cause of which is unknown. The aim of this study was to determine if anticipation was due to parkin mutation dosage. Methods We studied 19 kindreds that had early-onset parkinsonism in the offspring generation, late-onset parkinsonism in the parent generation, and ≥ 20 years of anticipation. We also studied 28 early-onset parkinsonism cases without anticipation. Patients were diagnosed by neurologists at a movement disorder clinic. parkin analysis included sequencing and dosage analysis of all 12 exons. Results Only one of 19 cases had compound parkin mutations, but contrary to our postulate, the affected relative with late-onset parkinsonism did not have a parkin mutation. In effect, none of the anticipation cases could be attributed to parkin. In contrast, 21% of early-onset parkinsonism patients without anticipation had parkin mutations. Conclusion Anticipation is not linked to parkin, and may signify a distinct disease entity.

Evaluation of students' knowledge about paediatric dosage calculations.

Science.gov (United States)

Özyazıcıoğlu, Nurcan; Aydın, Ayla İrem; Sürenler, Semra; Çinar, Hava Gökdere; Yılmaz, Dilek; Arkan, Burcu; Tunç, Gülseren Çıtak

2018-01-01

Medication errors are common and may jeopardize the patient safety. As paediatric dosages are calculated based on the child's age and weight, risk of error in dosage calculations is increasing. In paediatric patients, overdose drug prescribed regardless of the child's weight, age and clinical picture may lead to excessive toxicity and mortalities while low doses may delay the treatment. This study was carried out to evaluate the knowledge of nursing students about paediatric dosage calculations. This research, which is of retrospective type, covers a population consisting of all the 3rd grade students at the bachelor's degree in May, 2015 (148 students). Drug dose calculation questions in exam papers including 3 open ended questions on dosage calculation problems, addressing 5 variables were distributed to the students and their responses were evaluated by the researchers. In the evaluation of the data, figures and percentage distribution were calculated and Spearman correlation analysis was applied. Exam question on the dosage calculation based on child's age, which is the most common method in paediatrics, and which ensures right dosages and drug dilution was answered correctly by 87.1% of the students while 9.5% answered it wrong and 3.4% left it blank. 69.6% of the students was successful in finding the safe dose range, and 79.1% in finding the right ratio/proportion. 65.5% of the answers with regard to Ml/dzy calculation were correct. Moreover, student's four operation skills were assessed and 68.2% of the students were determined to have found the correct answer. When the relation among the questions on medication was examined, a significant relation (correlation) was determined between them. It is seen that in dosage calculations, the students failed mostly in calculating ml/dzy (decimal). This result means that as dosage calculations are based on decimal values, calculations may be ten times erroneous when the decimal point is placed wrongly. Moreover, it

Circadian rhythms and metabolic syndrome: from experimental genetics to human disease

OpenAIRE

Maury, Eleonore; Ramsey, Kathryn Moynihan; Bass, Joseph

2010-01-01

The incidence of the metabolic syndrome represents a spectrum of disorders that continue to increase across the industrialized world. Both genetic and environmental factors contribute to metabolic syndrome and recent evidence has emerged to suggest that alterations in circadian systems and sleep participate in the pathogenesis of the disease. In this review, we highlight studies at the intersection of clinical medicine and experimental genetics that pinpoint how perturbations of the internal ...

Metabolic Disturbances in Children with Chronic Liver Disease

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A Rezaeian

2014-04-01

Full Text Available Introduction: Liver disease results in complex pathophysiologic disturbances affecting nutrient digestion, absorption, distribution, storage, and use. This article aimed to present a classification of metabolic disturbances in chronic liver disease in children?   Materials and Methods: In this review study databases including proquest, pubmedcentral, scincedirect, ovid, medlineplus were been searched with keyword words such as” chronic liver disease"  ” metabolic disorder””children” between 1999 to 2014. Finally, 8 related articles have been found.   Results: Metabolic disorder in this population could be categorized in four set: 1carbohydrates, 2proteins,3 fats and 4vitamins. 1 Carbohydrates: Children with CLD are at increased risk for fasting hypoglycemia, because the capacity for glycogen storage and gluconeogenesis is reduced as a result of abnormal hepatocyte function and loss of hepatocyte mass. 2 Proteins: The liver’s capacity for plasma protein synthesis is impaired by reduced substrate availability, impaired hepatocyte function, and increased catabolism. This results in hypoalbuminemia, leading to peripheral edema and contributing to ascites. Reduced synthesis of insulin-like growth factor (IGF-1 and its binding protein IGF-BP3 by the chronically diseased liver results in growth hormone resistance and may contribute to the poor growth observed in these children. 3 Fats: There is increased fat oxidation in children with end-stage liver disease in the fed and fasting states compared with controls, which is probably related to reduced carbohydrate availability. The increased lipolysis results in a decrease in fat stores, which may not be easily replenished in the setting of the fat malabsorption that accompanies cholestasis. Reduced bile delivery to the gut results in impaired fat emulsification, and hence digestion. The products of fat digestion are also poorly absorbed, because bile is also required for micelle formation

Advances in solid dosage form manufacturing technology.

Science.gov (United States)

Andrews, Gavin P

2007-12-15

Currently, the pharmaceutical and healthcare industries are moving through a period of unparalleled change. Major multinational pharmaceutical companies are restructuring, consolidating, merging and more importantly critically assessing their competitiveness to ensure constant growth in an ever-more demanding market where the cost of developing novel products is continuously increasing. The pharmaceutical manufacturing processes currently in existence for the production of solid oral dosage forms are associated with significant disadvantages and in many instances provide many processing problems. Therefore, it is well accepted that there is an increasing need for alternative processes to dramatically improve powder processing, and more importantly to ensure that acceptable, reproducible solid dosage forms can be manufactured. Consequently, pharmaceutical companies are beginning to invest in innovative processes capable of producing solid dosage forms that better meet the needs of the patient while providing efficient manufacturing operations. This article discusses two emerging solid dosage form manufacturing technologies, namely hot-melt extrusion and fluidized hot-melt granulation.

Abnormal metabolic brain networks in Parkinson's disease from blackboard to bedside.

Science.gov (United States)

Tang, Chris C; Eidelberg, David

2010-01-01

Metabolic imaging in the rest state has provided valuable information concerning the abnormalities of regional brain function that underlie idiopathic Parkinson's disease (PD). Moreover, network modeling procedures, such as spatial covariance analysis, have further allowed for the quantification of these changes at the systems level. In recent years, we have utilized this strategy to identify and validate three discrete metabolic networks in PD associated with the motor and cognitive manifestations of the disease. In this chapter, we will review and compare the specific functional topographies underlying parkinsonian akinesia/rigidity, tremor, and cognitive disturbance. While network activity progressed over time, the rate of change for each pattern was distinctive and paralleled the development of the corresponding clinical symptoms in early-stage patients. This approach is already showing great promise in identifying individuals with prodromal manifestations of PD and in assessing the rate of progression before clinical onset. Network modulation was found to correlate with the clinical effects of dopaminergic treatment and surgical interventions, such as subthalamic nucleus (STN) deep brain stimulation (DBS) and gene therapy. Abnormal metabolic networks have also been identified for atypical parkinsonian syndromes, such as multiple system atrophy (MSA) and progressive supranuclear palsy (PSP). Using multiple disease-related networks for PD, MSA, and PSP, we have developed a novel, fully automated algorithm for accurate classification at the single-patient level, even at early disease stages. Copyright © 2010 Elsevier B.V. All rights reserved.

Identification of disease- and nutrient-related metabolic fingerprints in osteoarthritic guinea pigs

NARCIS (Netherlands)

Lamers, R.-J.A.N.; Groot, J. de; Spies-Faber, E.J.; Jellema, R.H.; Kraus, V.B.; Verzijl, N.; Koppele, J.M. te; Spijksma, G.K.; Vogels, J.T.W.E.; Greef, J. van der; Nesselrooij, J.H.J. van

2003-01-01

Osteoarthritis (OA), one of the most common diseases among the elderly, is characterized by the progressive destruction of joint tissues. Its etiology is largely unclear and no effective disease-modifying treatment is currently available. Metabolic fingerprinting provides a novel tool for the

Dosage sensitivity shapes the evolution of copy-number varied regions.

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Benjamin Schuster-Böckler

2010-03-01

Full Text Available Dosage sensitivity is an important evolutionary force which impacts on gene dispensability and duplicability. The newly available data on human copy-number variation (CNV allow an analysis of the most recent and ongoing evolution. Provided that heterozygous gene deletions and duplications actually change gene dosage, we expect to observe negative selection against CNVs encompassing dosage sensitive genes. In this study, we make use of several sources of population genetic data to identify selection on structural variations of dosage sensitive genes. We show that CNVs can directly affect expression levels of contained genes. We find that genes encoding members of protein complexes exhibit limited expression variation and overlap significantly with a manually derived set of dosage sensitive genes. We show that complexes and other dosage sensitive genes are underrepresented in CNV regions, with a particular bias against frequent variations and duplications. These results suggest that dosage sensitivity is a significant force of negative selection on regions of copy-number variation.

Lipid metabolism in peroxisomes in relation to human disease

NARCIS (Netherlands)

Wanders, R. J.; Tager, J. M.

1998-01-01

Peroxisomes were long believed to play only a minor role in cellular metabolism but it is now clear that they catalyze a number of important functions. The importance of peroxisomes in humans is stressed by the existence of a group of genetic diseases in man in which one or more peroxisomal

Occult Metabolic Bone Disease in Chronic Pancreatitis | Hari Kumar ...

African Journals Online (AJOL)

Background: Chronic pancreatitis (CP) leads to malabsorption and metabolic bone disease (MBD). Alcoholic CP (ACP) and tropical CP (TCP) are the two common types of CP. Objective: We investigated the presence of occult MBD in patients with CP and compared the same between ACP and TCP. Materials and Methods: ...

Genetic aspects of hypertension and metabolic disease in the obstructive sleep apnoea-hypopnoea syndrome

DEFF Research Database (Denmark)

Riha, R.L.; Diefenbach, K.; Jennum, P.

2008-01-01

Though it has long been recognised that there is a hereditary component to the obstructive steep apnoea/hypopnoea syndrome (OSAHS), identifying its genetic basis remains elusive. Hypertension and metabolic syndrome, Like OSAHS, are polygenic disorders, physiologically complex and the product...... phenotyping, which has hampered genetic dissection of these diseases; in addition, sleep-disordered breathing has not been factored into most studies dealing with essential hypertension or metabolic syndrome. Genome-wide scans have yielded inconsistent results in all three disorders under discussion...... for the expression of cardiovascular disease and metabolic syndrome in the context of OSAHS. (C) 2007 Elsevier Ltd. All rights reserved Udgivelsesdato: 2008/2...

A novel once daily microparticulate dosage form comprising lansoprazole to prevent nocturnal acid breakthrough in the case of gastro-esophageal reflux disease: preparation, pharmacokinetic and pharmacodynamic evaluation.

Science.gov (United States)

Alai, Milind; Lin, Wen Jen

2013-01-01

The objective of this study was to formulate and evaluate the lansoprazole (LPZ)-loaded microparticles to prevent nocturnal acid breakthrough in the case of gastro-esophageal reflux disease (GERD). The microparticulate delivery system was prepared by solvent evaporation method using Eudragit RS100 as a matrix polymer followed by enteric coated with Eudragit S100 and hydroxypropyl methylcellulose phthalate HP55 using spray drying method. The enteric coated microparticles were stable in gastric pH condition. In vivo pharmacokinetic and pharmacodynamic studies in male Wistar rats demonstrated that enteric coated microparticles sustained release of LPZ and promoted ulcer healing activity. In other words, the microparticulate dosage form provided effective drug concentration for a longer period as compared to conventional extended release dosage form, and showed sufficient anti-acid secretion activity to treat acid related disorders including the enrichment of nocturnal acid breakthrough event based on a once daily administration.

Microbial quality of some herbal solid dosage forms

African Journals Online (AJOL)

STORAGESEVER

2010-03-15

Mar 15, 2010 ... Key words: Microbial quality, herbal, contamination, solid dosage form ... The type of dosage form, packaging, manufacturing and expiration dates of subject solid herbal .... According to WHO report (2002), Salmonella food.

Parental genome dosage imbalance deregulates imprinting in Arabidopsis.

Directory of Open Access Journals (Sweden)

Pauline E Jullien

2010-03-01

Full Text Available In mammals and in plants, parental genome dosage imbalance deregulates embryo growth and might be involved in reproductive isolation between emerging new species. Increased dosage of maternal genomes represses growth while an increased dosage of paternal genomes has the opposite effect. These observations led to the discovery of imprinted genes, which are expressed by a single parental allele. It was further proposed in the frame of the parental conflict theory that parental genome imbalances are directly mirrored by antagonistic regulations of imprinted genes encoding maternal growth inhibitors and paternal growth enhancers. However these hypotheses were never tested directly. Here, we investigated the effect of parental genome imbalance on the expression of Arabidopsis imprinted genes FERTILIZATION INDEPENDENT SEED2 (FIS2 and FLOWERING WAGENINGEN (FWA controlled by DNA methylation, and MEDEA (MEA and PHERES1 (PHE1 controlled by histone methylation. Genome dosage imbalance deregulated the expression of FIS2 and PHE1 in an antagonistic manner. In addition increased dosage of inactive alleles caused a loss of imprinting of FIS2 and MEA. Although FIS2 controls histone methylation, which represses MEA and PHE1 expression, the changes of PHE1 and MEA expression could not be fully accounted for by the corresponding fluctuations of FIS2 expression. Our results show that parental genome dosage imbalance deregulates imprinting using mechanisms, which are independent from known regulators of imprinting. The complexity of the network of regulations between expressed and silenced alleles of imprinted genes activated in response to parental dosage imbalance does not support simple models derived from the parental conflict hypothesis.

Malavefes: A computational voice-enabled malaria fuzzy informatics software for correct dosage prescription of anti-malarial drugs

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Olugbenga O. Oluwagbemi

2018-04-01

Full Text Available Malaria is one of the infectious diseases consistently inherent in many Sub-Sahara African countries. Among the issues of concern are the consequences of wrong diagnosis and dosage administration of anti-malarial drugs on sick patients; these have resulted into various degrees of complications ranging from severe headaches, stomach and body discomfort, blurred vision, dizziness, hallucinations, and in extreme cases, death. Many expert systems have been developed to support different infectious disease diagnoses, but not sure of any yet, that have been specifically designed as a voice-based application to diagnose and translate malaria patients’ symptomatic data for pre-laboratory screening and correct prescription of proper dosage of the appropriate medication. We developed Malavefes, (a malaria voice-enabled computational fuzzy expert system for correct dosage prescription of anti-malarial drugs using Visual Basic.NET., and Java programming languages. Data collation for this research was conducted by survey from existing literature and interview from public health experts. The database for this malaria drug informatics system was implemented using Microsoft Access. The Root Sum Square (RSS was implemented as the inference engine of Malavefes to make inferences from rules, while Centre of Gravity (CoG was implemented as the defuzzification engine. The drug recommendation module was voice-enabled. Additional anti-malaria drug expiration validation software was developed using Java programming language. We conducted a user-evaluation of the performance and user-experience of the Malavefes software. Keywords: Informatics, Bioinformatics, Fuzzy, Anti-malaria, Voice computing, Dosage prescription

Race and ethnicity, obesity, metabolic health, and risk of cardiovascular disease in postmenopausal women

DEFF Research Database (Denmark)

Schmiegelow, Michelle D; Hedlin, Haley; Mackey, Rachel H

2015-01-01

BACKGROUND: It is unclear whether obesity unaccompanied by metabolic abnormalities is associated with increased cardiovascular disease risk across racial and ethnic subgroups. METHODS AND RESULTS: We identified 14 364 postmenopausal women from the Women's Health Initiative who had data on fasting...... serum lipids and serum glucose and no history of cardiovascular disease or diabetes at baseline. We categorized women by body mass index (in kg/m(2)) as normal weight (body mass index 18.5 to obese (body mass index ≥30) and by metabolic health, defined......, overweight women had similar risk to normal weight women (HR 0.92, interaction P=0.05). Obese black women without metabolic syndrome had higher adjusted risk (HR 1.95) than obese white women (HR 1.07; interaction P=0.02). Among women with only 2 metabolic abnormalities, cardiovascular risk was increased...

Proton magnetic resonance spectroscopy reflects metabolic decompensation in maple syrup urine disease

International Nuclear Information System (INIS)

Heindel, W.; Kugel, H.; Wendel, U.; Roth, B.; Benz-Bohm, G.

1995-01-01

Using localized proton magnetic resonance spectroscopy ( 1 H-MRS), accumulation of branchedchain amino acids (BCAA) and their corresponding 2-oxo acids (BCOA) could be non-invasively demonstrated in the brain of a 9-year-old girl suffering from classical maple syrup urine disease. During acute metabolic decompensation, the compounds caused a signal at a chemical shift of 0.9 ppm which was assigned by in vitro experiments. The brain tissue concentration of the sum of BCAA and BCOA could be estimated as 0.9 mmol/l. Localized 1 H-MRS of the brain appears to be suitable for examining patients suffering from maple syrup urine disease in different metabolic states. (orig.)

Diet-induced metabolic hamster model of nonalcoholic fatty liver disease

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Bhathena J

2011-06-01

Full Text Available Jasmine Bhathena, Arun Kulamarva, Christopher Martoni, Aleksandra Malgorzata Urbanska, Meenakshi Malhotra, Arghya Paul, Satya PrakashBiomedical Technology and Cell Therapy Research Laboratory, Department of Biomedical Engineering, Artificial Cells and Organs Research Centre, Faculty of Medicine, McGill University, Montreal, Québec, CanadaBackground: Obesity, hypercholesterolemia, elevated triglycerides, and type 2 diabetes are major risk factors for metabolic syndrome. Hamsters, unlike rats or mice, respond well to diet-induced obesity, increase body mass and adiposity on group housing, and increase food intake due to social confrontation-induced stress. They have a cardiovascular and hepatic system similar to that of humans, and can thus be a useful model for human pathophysiology.Methods: Experiments were planned to develop a diet-induced Bio F1B Golden Syrian hamster model of dyslipidemia and associated nonalcoholic fatty liver disease in the metabolic syndrome. Hamsters were fed a normal control diet, a high-fat/high-cholesterol diet, a high-fat/high-cholesterol/methionine-deficient/choline-devoid diet, and a high-fat/high-cholesterol/choline-deficient diet. Serum total cholesterol, high-density lipoprotein cholesterol, low-density lipoprotein cholesterol, triglycerides, glucose, atherogenic index, and body weight were quantified biweekly. Fat deposition in the liver was observed and assessed following lipid staining with hematoxylin and eosin and with oil red O.Results: In this study, we established a diet-induced Bio F1B Golden Syrian hamster model for studying dyslipidemia and associated nonalcoholic fatty liver disease in the metabolic syndrome. Hyperlipidemia and elevated serum glucose concentrations were induced using this diet. Atherogenic index was elevated, increasing the risk for a cardiovascular event. Histological analysis of liver specimens at the end of four weeks showed increased fat deposition in the liver of animals fed

Multiple-trait estimates of genetic parameters for metabolic disease traits, fertility disorders, and their predictors in Canadian Holsteins.

Science.gov (United States)

Jamrozik, J; Koeck, A; Kistemaker, G J; Miglior, F

2016-03-01

Producer-recorded health data for metabolic disease traits and fertility disorders on 35,575 Canadian Holstein cows were jointly analyzed with selected indicator traits. Metabolic diseases included clinical ketosis (KET) and displaced abomasum (DA); fertility disorders were metritis (MET) and retained placenta (RP); and disease indicators were fat-to-protein ratio, milk β-hydroxybutyrate, and body condition score (BCS) in the first lactation. Traits in first and later (up to fifth) lactations were treated as correlated in the multiple-trait (13 traits in total) animal linear model. Bayesian methods with Gibbs sampling were implemented for the analysis. Estimates of heritability for disease incidence were low, up to 0.06 for DA in first lactation. Among disease traits, the environmental herd-year variance constituted 4% of the total variance for KET and less for other traits. First- and later-lactation disease traits were genetically correlated (from 0.66 to 0.72) across all traits, indicating different genetic backgrounds for first and later lactations. Genetic correlations between KET and DA were relatively strong and positive (up to 0.79) in both first- and later-lactation cows. Genetic correlations between fertility disorders were slightly lower. Metritis was strongly genetically correlated with both metabolic disease traits in the first lactation only. All other genetic correlations between metabolic and fertility diseases were statistically nonsignificant. First-lactation KET and MET were strongly positively correlated with later-lactation performance for these traits due to the environmental herd-year effect. Indicator traits were moderately genetically correlated (from 0.30 to 0.63 in absolute values) with both metabolic disease traits in the first lactation. Smaller and mostly nonsignificant genetic correlations were among indicators and metabolic diseases in later lactations. The only significant genetic correlations between indicators and fertility

Calcium Regulation and Bone Mineral Metabolism in Elderly Patients with Chronic Kidney Disease

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Vickram Tejwani

2013-05-01

Full Text Available The elderly chronic kidney disease (CKD population is growing. Both aging and CKD can disrupt calcium (Ca2+ homeostasis and cause alterations of multiple Ca2+-regulatory mechanisms, including parathyroid hormone, vitamin D, fibroblast growth factor-23/Klotho, calcium-sensing receptor and Ca2+-phosphate product. These alterations can be deleterious to bone mineral metabolism and soft tissue health, leading to metabolic bone disease and vascular calcification and aging, termed CKD-mineral and bone disorder (MBD. CKD-MBD is associated with morbid clinical outcomes, including fracture, cardiovascular events and all-cause mortality. In this paper, we comprehensively review Ca2+ regulation and bone mineral metabolism, with a special emphasis on elderly CKD patients. We also present the current treatment-guidelines and management options for CKD-MBD.

Cerebral glucose metabolic patterns in Alzheimer's disease. Effect of gender and age at dementia onset

International Nuclear Information System (INIS)

Small, G.W.; Kuhl, D.E.; Riege, W.H.; Fujikawa, D.G.; Ashford, J.W.; Metter, E.J.; Mazziotta, J.C.

1989-01-01

No previous study of Alzheimer's disease has, to our knowledge, assessed the effect of both age at dementia onset and gender on cerebral glucose metabolic patterns. To this end, we used positron emission tomography (fludeoxyglucose F 18 method) to study 24 patients with clinical diagnoses of probable Alzheimer's disease. Comparisons of the 13 patients with early-onset dementia (less than 65 years of age) with the 11 patients with late-onset dementia (greater than 65 years of age) revealed significantly lower left parietal metabolic ratios (left posterior parietal region divided by the hemispheric average) in the early-onset group. The metabolic ratio of posterior parietal cortex divided by the relatively disease-stable average of caudate and thalamus also separated patients with early-onset dementia from those with late-onset dementia, but not men from women. Further comparisons between sexes showed that, in all brain regions studied, the 9 postmenopausal women had higher nonweighted mean metabolic rates than the 15 men from the same age group, with hemispheric sex differences of 9% on the right and 7% on the left. These results demonstrate decreased parietal ratios in early-onset dementia of Alzheimer's disease, independent of a gender effect

The relationship between metabolic acidosis and nutritional parameters in patients on hemodialysis

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A D Sajgure

2017-01-01

Full Text Available The progressive loss of kidney function is accompanied by metabolic acidosis. The relationship between metabolic acidosis, nutritional status, and oral bicarbonate supplementation has not been assessed in the Indian chronic kidney disease (CKD population who are on maintenance hemodialysis (MHD. This is a single-center prospective study conducted in the Western part of India. Thirty-five patients, who were receiving MHD were assessed for metabolic acidosis along with various nutritional parameters at the baseline and at the follow-up after 3 months, postcorrection of acidosis with oral sodium bicarbonate supplements. The relationship between the correction of metabolic acidosis with oral bicarbonate supplements and changes in dietary and various nutritional parameters were evaluated. Metabolic acidosis at the baseline evaluation was found in 62.86% cases of the cohort with a mean serum bicarbonate value of 20.18 ± 4.93 mmol/L. The correction of acidosis with increment in the mean dosage of oral sodium bicarbonate supplements from 0.69 ± 0.410 mmol/kg/day at baseline to 1.04 ± 0.612 mmol/kg/day, significantly reduced the prevalence of metabolic acidosis to 23.33% cases at the follow-up. Improvement in serum bicarbonate level showed significant dietary, anthropometric, and nutritional improvements in these patients. Hence, we conclude that correction of metabolic acidosis with optimal oral bicarbonate supplementation plays a pivotal role in the treatment of malnourished CKD patients on MHD.

21 CFR 520.905 - Fenbendazole oral dosage forms.

Science.gov (United States)

2010-04-01

... 21 Food and Drugs 6 2010-04-01 2010-04-01 false Fenbendazole oral dosage forms. 520.905 Section 520.905 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES... Fenbendazole oral dosage forms. ...

Buccal Dosage Forms: General Considerations for Pediatric Patients.

Science.gov (United States)

Montero-Padilla, Soledad; Velaga, Sitaram; Morales, Javier O

2017-02-01

The development of an appropriate dosage form for pediatric patients needs to take into account several aspects, since adult drug biodistribution differs from that of pediatrics. In recent years, buccal administration has become an attractive route, having different dosage forms under development including tablets, lozenges, films, and solutions among others. Furthermore, the buccal epithelium can allow quick access to systemic circulation, which could be used for a rapid onset of action. For pediatric patients, dosage forms to be placed in the oral cavity have higher requirements for palatability to increase acceptance and therapy compliance. Therefore, an understanding of the excipients required and their functions and properties needs to be particularly addressed. This review is focused on the differences and requirements relevant to buccal administration for pediatric patients (compared to adults) and how novel dosage forms can be less invasive and more acceptable alternatives.

Therapeutic Roles of Heme Oxygenase-1 in Metabolic Diseases: Curcumin and Resveratrol Analogues as Possible Inducers of Heme Oxygenase-1

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Yong Son

2013-01-01

Full Text Available Metabolic diseases, such as insulin resistance, type II diabetes, and obesity, are associated with a low-grade chronic inflammation (inflammatory stress, oxidative stress, and endoplasmic reticulum (ER stress. Because the integration of these stresses is critical to the pathogenesis of metabolic diseases, agents and cellular molecules that can modulate these stress responses are emerging as potential targets for intervention and treatment of metabolic diseases. It has been recognized that heme oxygenase-1 (HO-1 plays an important role in cellular protection. Because HO-1 can reduce inflammatory stress, oxidative stress, and ER stress, in part by exerting antioxidant, anti-inflammatory, and antiapoptotic effects, HO-1 has been suggested to play important roles in pathogenesis of metabolic diseases. In the present review, we will explore our current understanding of the protective mechanisms of HO-1 in metabolic diseases and present some emerging therapeutic options for HO-1 expression in treating metabolic diseases, together with the therapeutic potential of curcumin and resveratrol analogues that have their ability to induce HO-1 expression.

Intercavitary implants dosage calculation

International Nuclear Information System (INIS)

Rehder, B.P.

The use of spacial geometry peculiar to each treatment for the attainment of intercavitary and intersticial implants dosage calculation is presented. The study is made in patients with intercavitary implants by applying a modified Manchester technique [pt

21 CFR 522.1660 - Oxytetracycline injectable dosage forms.

Science.gov (United States)

2010-04-01

... 21 Food and Drugs 6 2010-04-01 2010-04-01 false Oxytetracycline injectable dosage forms. 522.1660 Section 522.1660 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES... § 522.1660 Oxytetracycline injectable dosage forms. ...

Effectiveness of different benfotiamine dosage regimens in the treatment of painful diabetic neuropathy.

Science.gov (United States)

Winkler, G; Pál, B; Nagybéganyi, E; Ory, I; Porochnavec, M; Kempler, P

1999-03-01

The therapeutic effectiveness of a benfotiamine (CAS 22457-89-2)-vitamin B combination (Milgamma-N), administered in high (4 x 2 capsules/day, = 320 mg benfotiamine/day) and medium doses (3 x 1 capsules/day), was compared to a monotherapy with benfotiamine (Benfogamma) (3 x 1 tablets/day, = 150 mg benfotiamine/day) in diabetic patients suffering from painful peripheral diabetic neuropathy (DNP). In a 6-week open clinical trial, 36 patients (aged 40 to 70 yrs) having acceptable metabolic control (HbA1c benfotiamine (p benfotiamine is most effective in large doses, although even in smaller daily dosages, either in combination or in monotherapy, it is effective.

Hyperpolarized metabolic MR in the study of cardiac function and disease

DEFF Research Database (Denmark)

Lauritzen, M. H.; Søgaard, L. V.; Madsen, Pia Lisbeth

2014-01-01

Several diseases of the heart have been linked to an insufficient ability to generate enough energy (ATP) to sustain proper heart function. Hyperpolarized magnetic resonance (MR) is a novel technique that can visualize and quantify myocardial energy metabolism. Hyperpolarization enhances the MR...... signal from a biological molecule of interest by more than 10,000 times, making it possible to measure its cellular uptake and conversion in specific enzymatic pathways in real time. We review the role of hyperpolarized MR in identifying changes in cardiac metabolism in vivo, and present the extensive...... literature on hyperpolarized pyruvate that has been used to characterize cardiac disease in various in vivo models, such as myocardial ischemia, hypertension, diabetes, hyperthyroidism and heart failure. The technical aspects of the technique are presented as well as the challenges of translating...

Relationship between hepatocellular carcinoma, metabolic syndrome and non-alcoholic fatty liver disease: which clinical arguments?

Science.gov (United States)

Rosmorduc, Olivier

2013-05-01

Obesity and the metabolic syndrome are growing epidemics associated with an increased risk for many types of cancer. In the liver, inflammatory and angiogenic changes due to insulin resistance and fatty liver disease are associated with an increased incidence of liver cancer. Regardless of underlying liver disease, cirrhosis remains the most important risk factor for hepatocellular carcinoma (HCC) although are cases of HCC arising without cirrhosis raise the possibility of a direct carcinogenesis secondary to Non-alcoholic Fatty Liver Disease (NAFLD). Moreover, metabolic syndrome and its different features may also increase the risk of HCC in the setting of chronic liver diseases of other causes such as viral hepatitis or alcohol abuse. Taking into account all these data, it is necessary to better determine the risk of developing HCC in patients with metabolic syndrome to improve the screening guidelines and develop prophylactic treatments in this setting. Copyright © 2013 Elsevier Masson SAS. All rights reserved.

Radiation dosage

Energy Technology Data Exchange (ETDEWEB)

Finston, Roland [Health Physics, Stanford University, Stanford, CA (United States)

1986-07-01

Radiation dosage at Bikini Atoll is the result of current soil contamination, a relic of the nuclear weapons testing program of some 30 years ago. The principal contaminants today and some of their physical properties are listed: cesium-137, strontium-90, plutonium -239, 240 and americium-241. Cobalt-60 contributes less than 1 to the dose and is not considered significant. A resident of the atoll would accumulate radiation dose (rem) in two ways -- by exposure to radiation emanating from the ground and vegetation, and by exposure to radiation released in the spontaneous decay of radionuclides that have entered his body during the ingestion of locally grown foods. The latter process would account for some 90% of the dose; cesium-137 would be responsible for 0 90% of it. Since BARC's method of estimating dosage differs in some respects from that employed by the Lawrence Livermore National Laboratory (LLNL), (Ref.1, LLNL 1982) we are presenting our method in detail. The differences have two sources. First, the numbers used by BARC for the daily ingestion of radionuclides via the diet are higher than LLNL's. Second, BARC's calculation of dose from radionuclide intake utilizes the ICRP system. The net result is that BARC doses are consistently higher than LLNL doses, and in this respect are more conservative.

Radiation dosage

International Nuclear Information System (INIS)

Finston, Roland

1986-01-01

Radiation dosage at Bikini Atoll is the result of current soil contamination, a relic of the nuclear weapons testing program of some 30 years ago. The principal contaminants today and some of their physical properties are listed: cesium-137, strontium-90, plutonium -239, 240 and americium-241. Cobalt-60 contributes less than 1 to the dose and is not considered significant. A resident of the atoll would accumulate radiation dose (rem) in two ways -- by exposure to radiation emanating from the ground and vegetation, and by exposure to radiation released in the spontaneous decay of radionuclides that have entered his body during the ingestion of locally grown foods. The latter process would account for some 90% of the dose; cesium-137 would be responsible for 0 90% of it. Since BARC's method of estimating dosage differs in some respects from that employed by the Lawrence Livermore National Laboratory (LLNL), (Ref.1, LLNL 1982) we are presenting our method in detail. The differences have two sources. First, the numbers used by BARC for the daily ingestion of radionuclides via the diet are higher than LLNL's. Second, BARC's calculation of dose from radionuclide intake utilizes the ICRP system. The net result is that BARC doses are consistently higher than LLNL doses, and in this respect are more conservative

Radiation dosage of various CT-methods in lung diagnostics

International Nuclear Information System (INIS)

Heinz-Peer, G.; Weninger, F.; Nowotny, R.; Herold, C.J.

1996-01-01

Introduction of the computed tomography index CTDI and the multiple scan average dose (MSAD) has led to standardization of the dose description in CT examinations. Despite the use of these dose parameters, many different dosages are reported in the literature for different CT methods. In addition, there is still a wide range of radiation dosimetry results reported for conventional CT, helical CT, and HRCT used in chest examinations. The variations in dosage are mainly due to difference in factors affecting the dose, i.e. beam geometry, beam quality, scanner geometry ('generation'), and operating parameters. In addition, CT dosimetry instrumentation and methodology make a contribution to dosages. Recent studies calculating differences in factors affecting dosage and CT dosimetry and using similar operating parameters, show similar results in CT dosimetry for conventional and helical CT. On the other hand, dosages for HRCT were greatly reduced. This was mainly caused by narrow beam collimation and increasing section spacing. (orig.) [de

Hydraulic Modular Dosaging Systems for Machine Drives

Directory of Open Access Journals (Sweden)

A. J. Kotlobai

2005-01-01

Full Text Available The justified principle of making modular dosaging systems for positive-displacement multimotor hydraulic drives used in running gear and technological equipment of mobile construction, road and agricultural machines makes it possible to synchronize motion of running parts. The examples of the realization of modular dosaging systems and an algorithm of their operation are given in the paper.

Proton magnetic resonance spectroscopy reflects metabolic decompensation in maple syrup urine disease

Energy Technology Data Exchange (ETDEWEB)

Heindel, W. [Dept. of Diagnostic Radiology, Univ. Koeln (Germany); Kugel, H. [Dept. of Diagnostic Radiology, Univ. Koeln (Germany); Wendel, U. [Children`s Hospital, Univ. Duesseldorf (Germany); Roth, B. [Children`s Hospital, Univ. Koeln (Germany); Benz-Bohm, G. [Dept. of Diagnostic Radiology, Univ. Koeln (Germany)

1995-06-01

Using localized proton magnetic resonance spectroscopy ({sup 1}H-MRS), accumulation of branchedchain amino acids (BCAA) and their corresponding 2-oxo acids (BCOA) could be non-invasively demonstrated in the brain of a 9-year-old girl suffering from classical maple syrup urine disease. During acute metabolic decompensation, the compounds caused a signal at a chemical shift of 0.9 ppm which was assigned by in vitro experiments. The brain tissue concentration of the sum of BCAA and BCOA could be estimated as 0.9 mmol/l. Localized {sup 1}H-MRS of the brain appears to be suitable for examining patients suffering from maple syrup urine disease in different metabolic states. (orig.)

Correlated changes of serum sFas/sFasL and TRAb concentrations in patients with Graves' disease after treatment with lesser dosage of 131i combined with traditional Chinese medicine

International Nuclear Information System (INIS)

Zhang Jinshan; Deng Yongmei; Li Min; Huang Guimin; Feng Chonglian

2005-01-01

Objective: To investigate the rule of changes of serum sFas/sFasL and TRAb concentrations in patients with Graves' disease after treatment with lesser dosage of 131 I combined with traditional chinese medicine. Methods: Thirty-one patients with Graves' disease were treated with a lesser dosage (85.1-207.2 MBq, mean--about 2/3 of conventional dose) of 131 I combined with traditional chinese medicine. Serum sFas, sFasL (with ELISA), TRAb (with RRA) and other thyroid-related hormones (TT 3 , TT 4 , FT 3 , FT 4 , TSH, TGA, TMA with RIA) concentrations were determined before and after the treatment. Seventeen controls participated in this experiment. Results: 1) Serum sFas contents in the patients before treatment (179.8 ± 64.2 pg/ml) were significantly higher than those in patients clinically cured (104.2 ± 23.5 pg/ml) and controls (110.6 ± 18.1 pg/ml) (both P 131 I and traditional chinese medicine was satisfactory. The treatment was immediately effective in 100% of the patients (31/31) with a permanent cure rate of 74.2% (23/31) (one dose only) and late hypothyroidism rate of 9.7% (3/31). Conclusion: Reversal of the dominant expression of sFas after the combined treatment indirectly showed the role of apoptosis in the cure of Graves' disease. TRAb was a practical laboratory diagnostic criterion for Graves' disease. (authors)

Population newborn screening for inherited metabolic disease: current UK perspectives.

Science.gov (United States)

Green, A; Pollitt, R J

1999-06-01

Some of the generally accepted criteria for screening programmes are inappropriate for newborn metabolic screening as they ignore the family dimension and the importance of timely genetic information. Uncritical application of such criteria creates special difficulties for screening by tandem mass spectrometry, which can detect a range diseases with widely different natural histories and responsiveness to treatment. Further difficulties arise from increasing demands for direct proof of the effects of screening on long-term morbidity and mortality. The randomized controlled trial is held to be the gold standard, but for ethical and practical reasons it will be impossible to achieve for such relatively rare diseases. This approach also oversimplifies the complex matrix of costs and benefits of newborn metabolic screening. A more workable approach could involve Bayesian synthesis, combining quantitative performance data from carefully designed prospective pilot studies of screening with existing experience of the natural history, diagnosis, and management of the individual disorders concerned.

Energy metabolism and inflammation in brain aging and Alzheimer's disease.

Science.gov (United States)

Yin, Fei; Sancheti, Harsh; Patil, Ishan; Cadenas, Enrique

2016-11-01

The high energy demand of the brain renders it sensitive to changes in energy fuel supply and mitochondrial function. Deficits in glucose availability and mitochondrial function are well-known hallmarks of brain aging and are particularly accentuated in neurodegenerative disorders such as Alzheimer's disease. As important cellular sources of H 2 O 2 , mitochondrial dysfunction is usually associated with altered redox status. Bioenergetic deficits and chronic oxidative stress are both major contributors to cognitive decline associated with brain aging and Alzheimer's disease. Neuroinflammatory changes, including microglial activation and production of inflammatory cytokines, are observed in neurodegenerative diseases and normal aging. The bioenergetic hypothesis advocates for sequential events from metabolic deficits to propagation of neuronal dysfunction, to aging, and to neurodegeneration, while the inflammatory hypothesis supports microglia activation as the driving force for neuroinflammation. Nevertheless, growing evidence suggests that these diverse mechanisms have redox dysregulation as a common denominator and connector. An independent view of the mechanisms underlying brain aging and neurodegeneration is being replaced by one that entails multiple mechanisms coordinating and interacting with each other. This review focuses on the alterations in energy metabolism and inflammatory responses and their connection via redox regulation in normal brain aging and Alzheimer's disease. Interaction of these systems is reviewed based on basic research and clinical studies. Copyright © 2016 Elsevier Inc. All rights reserved.

Completeness of metabolic disease recordings in Nordic national databases for dairy cows.

Science.gov (United States)

Espetvedt, M N; Wolff, C; Rintakoski, S; Lind, A; Østerås, O

2012-06-01

The four Nordic countries Denmark (DK), Finland (FI), Norway (NO) and Sweden (SE) all have national databases where diagnostic events in dairy cows are recorded. Comparing and looking at differences in disease occurrence between countries may give information on factors that influence disease occurrence, optimal diseases control and treatment strategies. For such comparisons to be valid, the data in these databases should be standardised and of good quality. The objective of the study presented here was to assess the quality of metabolic disease recordings, primarily milk fever and ketosis, in four Nordic national databases. Completeness of recording figures of database registrations at two different levels was chosen as a measure of data quality. Firstly, completeness of recording of all disease events on a farm regardless of veterinary involvement, called 'Farmer observed completeness', was determined. Secondly, completeness of recording of veterinary treated disease events only, called 'Veterinary treated completeness', was determined. To collect data for calculating these completeness levels a simple random sample of herds was obtained in each country. Farmers who were willing to participate, recorded for 4 months in 2008, on a purpose made registration form, any observed illness in cows, regardless of veterinary involvement. The number of participating herds was 105, 167, 179 and 129 in DK, FI, NO and SE respectively. In total these herds registered 247, 248, 177 and 218 metabolic events for analysis in DK, FI, NO and SE, respectively. Data from national databases were subsequently extracted, and the two sources of data were matched to find the proportion, or completeness, of diagnostic events registered by farmers that also existed in national databases. Matching was done using a common diagnostic code system and allowed for a discrepancy of 7 days for registered date of the event. For milk fever, the Farmer observed completeness was 77%, 67%, 79% and 79

Carbohydrate-Restriction with High-Intensity Interval Training: An Optimal Combination for Treating Metabolic Diseases?

Directory of Open Access Journals (Sweden)

Monique E. Francois

2017-10-01

Full Text Available Lifestyle interventions incorporating both diet and exercise strategies remain cornerstone therapies for treating metabolic disease. Carbohydrate-restriction and high-intensity interval training (HIIT have independently been shown to improve cardiovascular and metabolic health. Carbohydrate-restriction reduces postprandial hyperglycemia, thereby limiting potential deleterious metabolic and cardiovascular consequences of excessive glucose excursions. Additionally, carbohydrate-restriction has been shown to improve body composition and blood lipids. The benefits of exercise for improving insulin sensitivity are well known. In this regard, HIIT has been shown to rapidly improve glucose control, endothelial function, and cardiorespiratory fitness. Here, we report the available evidence for each strategy and speculate that the combination of carbohydrate-restriction and HIIT will synergistically maximize the benefits of both approaches. We hypothesize that this lifestyle strategy represents an optimal intervention to treat metabolic disease; however, further research is warranted in order to harness the potential benefits of carbohydrate-restriction and HIIT for improving cardiometabolic health.

Carbohydrate-Restriction with High-Intensity Interval Training: An Optimal Combination for Treating Metabolic Diseases?

Science.gov (United States)

Francois, Monique E; Gillen, Jenna B; Little, Jonathan P

2017-01-01

Lifestyle interventions incorporating both diet and exercise strategies remain cornerstone therapies for treating metabolic disease. Carbohydrate-restriction and high-intensity interval training (HIIT) have independently been shown to improve cardiovascular and metabolic health. Carbohydrate-restriction reduces postprandial hyperglycemia, thereby limiting potential deleterious metabolic and cardiovascular consequences of excessive glucose excursions. Additionally, carbohydrate-restriction has been shown to improve body composition and blood lipids. The benefits of exercise for improving insulin sensitivity are well known. In this regard, HIIT has been shown to rapidly improve glucose control, endothelial function, and cardiorespiratory fitness. Here, we report the available evidence for each strategy and speculate that the combination of carbohydrate-restriction and HIIT will synergistically maximize the benefits of both approaches. We hypothesize that this lifestyle strategy represents an optimal intervention to treat metabolic disease; however, further research is warranted in order to harness the potential benefits of carbohydrate-restriction and HIIT for improving cardiometabolic health.

Prioritizing Candidate Disease Metabolites Based on Global Functional Relationships between Metabolites in the Context of Metabolic Pathways

Science.gov (United States)

Yang, Haixiu; Xu, Yanjun; Han, Junwei; Li, Jing; Su, Fei; Zhang, Yunpeng; Zhang, Chunlong; Li, Dongguo; Li, Xia

2014-01-01

Identification of key metabolites for complex diseases is a challenging task in today's medicine and biology. A special disease is usually caused by the alteration of a series of functional related metabolites having a global influence on the metabolic network. Moreover, the metabolites in the same metabolic pathway are often associated with the same or similar disease. Based on these functional relationships between metabolites in the context of metabolic pathways, we here presented a pathway-based random walk method called PROFANCY for prioritization of candidate disease metabolites. Our strategy not only takes advantage of the global functional relationships between metabolites but also sufficiently exploits the functionally modular nature of metabolic networks. Our approach proved successful in prioritizing known metabolites for 71 diseases with an AUC value of 0.895. We also assessed the performance of PROFANCY on 16 disease classes and found that 4 classes achieved an AUC value over 0.95. To investigate the robustness of the PROFANCY, we repeated all the analyses in two metabolic networks and obtained similar results. Then we applied our approach to Alzheimer's disease (AD) and found that a top ranked candidate was potentially related to AD but had not been reported previously. Furthermore, our method was applicable to prioritize the metabolites from metabolomic profiles of prostate cancer. The PROFANCY could identify prostate cancer related-metabolites that are supported by literatures but not considered to be significantly differential by traditional differential analysis. We also developed a freely accessible web-based and R-based tool at http://bioinfo.hrbmu.edu.cn/PROFANCY. PMID:25153931

Evaluation of Human Adipose Tissue Stromal Heterogeneity in Metabolic Disease Using Single Cell RNA-Seq

Science.gov (United States)

2017-09-01

AWARD NUMBER: W81XWH-15-1-0251 TITLE: “Evaluation of Human Adipose Tissue Stromal Heterogeneity in Metabolic Disease Using Single Cell RNA...Heterogeneity in Metabolic Disease Using Single- Cell RNA-Seq 5b. GRANT NUMBER 5c. PROGRAM ELEMENT NUMBER 6. AUTHOR(S) 5d. PROJECT NUMBER Linus Tzu-Yen...ABSTRACT We have developed a robust protocol to generate single cell transcriptional profiles from subcutaneous adipose tissue samples of both human

Maternal obesity increases the risk of metabolic disease and impacts renal health in offspring

Science.gov (United States)

Glastras, Sarah J.; Chen, Hui; Pollock, Carol A.; Saad, Sonia

2018-01-01

Obesity, together with insulin resistance, promotes multiple metabolic abnormalities and is strongly associated with an increased risk of chronic disease including type 2 diabetes (T2D), hypertension, cardiovascular disease, non-alcoholic fatty liver disease (NAFLD) and chronic kidney disease (CKD). The incidence of obesity continues to rise in astronomical proportions throughout the world and affects all the different stages of the lifespan. Importantly, the proportion of women of reproductive age who are overweight or obese is increasing at an alarming rate and has potential ramifications for offspring health and disease risk. Evidence suggests a strong link between the intrauterine environment and disease programming. The current review will describe the importance of the intrauterine environment in the development of metabolic disease, including kidney disease. It will detail the known mechanisms of fetal programming, including the role of epigenetic modulation. The evidence for the role of maternal obesity in the developmental programming of CKD is derived mostly from our rodent models which will be described. The clinical implication of such findings will also be discussed. PMID:29483369

Disturbed Vitamin A Metabolism in Non-Alcoholic Fatty Liver Disease (NAFLD

Directory of Open Access Journals (Sweden)

Ali Saeed

2017-12-01

Full Text Available Vitamin A is required for important physiological processes, including embryogenesis, vision, cell proliferation and differentiation, immune regulation, and glucose and lipid metabolism. Many of vitamin A’s functions are executed through retinoic acids that activate transcriptional networks controlled by retinoic acid receptors (RARs and retinoid X receptors (RXRs.The liver plays a central role in vitamin A metabolism: (1 it produces bile supporting efficient intestinal absorption of fat-soluble nutrients like vitamin A; (2 it produces retinol binding protein 4 (RBP4 that distributes vitamin A, as retinol, to peripheral tissues; and (3 it harbors the largest body supply of vitamin A, mostly as retinyl esters, in hepatic stellate cells (HSCs. In times of inadequate dietary intake, the liver maintains stable circulating retinol levels of approximately 2 μmol/L, sufficient to provide the body with this vitamin for months. Liver diseases, in particular those leading to fibrosis and cirrhosis, are associated with impaired vitamin A homeostasis and may lead to vitamin A deficiency. Liver injury triggers HSCs to transdifferentiate to myofibroblasts that produce excessive amounts of extracellular matrix, leading to fibrosis. HSCs lose the retinyl ester stores in this process, ultimately leading to vitamin A deficiency. Non-alcoholic fatty liver disease (NAFLD is the hepatic manifestation of metabolic syndrome and is a spectrum of conditions ranging from benign hepatic steatosis to non-alcoholic steatohepatitis (NASH; it may progress to cirrhosis and liver cancer. NASH is projected to be the main cause of liver failure in the near future. Retinoic acids are key regulators of glucose and lipid metabolism in the liver and adipose tissue, but it is unknown whether impaired vitamin A homeostasis contributes to or suppresses the development of NAFLD. A genetic variant of patatin-like phospholipase domain-containing 3 (PNPLA3-I148M is the most prominent

21 CFR 526.1696 - Penicillin intramammary dosage forms.

Science.gov (United States)

2010-04-01

... 21 Food and Drugs 6 2010-04-01 2010-04-01 false Penicillin intramammary dosage forms. 526.1696 Section 526.1696 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED) ANIMAL DRUGS, FEEDS, AND RELATED PRODUCTS INTRAMAMMARY DOSAGE FORMS § 526.1696 Penicillin...

Metabolic syndrome and dementia associated with Parkinson's disease: impact of age and hypertension

Directory of Open Access Journals (Sweden)

Arthur Oscar Schelp

2012-02-01

Full Text Available OBJECTIVE: To determine correlations between age and metabolic disorders in Parkinson's disease (PD patients. METHODS: This observational cross-sectional study included brief tests for dementia and the Mattis test. Signals of metabolic syndrome were evaluated. RESULTS: There was no significant effect from the presence of hypertension (OR=2.36 for patients under 65 years old and OR=0.64 for patients over 65, diabetes or hypercholesterolemia regarding occurrences of dementia associated with PD (24% of the patients. The study demonstrated that each year of age increased the estimated risk of dementia in PD patients by 9% (OR=1.09; 95%CI: 1.01-1.17. CONCLUSION: There was no evidence to correlate the presence of metabolic syndrome with the risk of dementia that was associated with PD. The study confirmed that dementia in PD is age dependent and not related to disease duration.

Pathophysiology and therapeutics of cardiovascular disease in metabolic syndrome.

Science.gov (United States)

Wang, Yabin; Yu, Qiujun; Chen, Yundai; Cao, Feng

2013-01-01

The metabolic syndrome (MetS) is characterized by a cluster of cardiovascular risk factors, including central obesity, hyperglycemia, dyslipidemia and hypertension, which are highly associated with increased morbidity and mortality of cardiovascular diseases (CVD). The association between these metabolic disorders and the development of CVD is believed to be multifactorial, where insulin resistance, oxidative stress, low-grade inflammation and vascular maladaptation act as the major contributors. Therefore, multipronged therapeutic strategies should be taken for the management of patients with MetS. Lifestyle changes including weight control, healthy heart diet and regular exercises have been proposed as first line treatment to decrease CVD risks in MetS individuals. In addition, improving insulin resistance and glucose metabolism, controlling blood pressure as well as modulating dyslipidemia can also delay or reverse the progression of CVD in MetS. This review will first address the complicated interactions between MetS and CVD¸ followed by discussion about the optimal strategy in the prevention and treatment of CVD in MetS patients and the updated results from newly released clinical trials.

The consequences of chronic kidney disease on bone metabolism and growth in children.

Science.gov (United States)

Bacchetta, Justine; Harambat, Jérôme; Cochat, Pierre; Salusky, Isidro B; Wesseling-Perry, Katherine

2012-08-01

Growth retardation, decreased final height and renal osteodystrophy (ROD) are common complications of childhood chronic kidney disease (CKD), resulting from a combination of abnormalities in the growth hormone (GH) axis, vitamin D deficiency, hyperparathyroidism, hypogonadism, inadequate nutrition, cachexia and drug toxicity. The impact of CKD-associated bone and mineral disorders (CKD-MBD) may be immediate (serum phosphate/calcium disequilibrium) or delayed (poor growth, ROD, fractures, vascular calcifications, increased morbidity and mortality). In 2012, the clinical management of CKD-MBD in children needs to focus on three main objectives: (i) to provide an optimal growth in order to maximize the final height with an early management with recombinant GH therapy when required, (ii) to equilibrate calcium/phosphate metabolism so as to obtain acceptable bone quality and cardiovascular status and (iii) to correct all metabolic and clinical abnormalities that can worsen bone disease, growth and cardiovascular disease, i.e. metabolic acidosis, anaemia, malnutrition and 25(OH)vitamin D deficiency. The aim of this review is to provide an overview of the mineral, bone and vascular abnormalities associated with CKD in children in terms of pathophysiology, diagnosis and clinical management.

Dynamic relationships between age, amyloid-β deposition, and glucose metabolism link to the regional vulnerability to Alzheimer’s disease

Science.gov (United States)

Madison, Cindee; Baker, Suzanne; Rabinovici, Gil; Jagust, William

2016-01-01

Abstract See Hansson and Gouras (doi:10.1093/aww146) for a scientific commentary on this article. Although some brain regions such as precuneus and lateral temporo-parietal cortex have been shown to be more vulnerable to Alzheimer’s disease than other areas, a mechanism underlying the differential regional vulnerability to Alzheimer’s disease remains to be elucidated. Using fluorodeoxyglucose and Pittsburgh compound B positron emission tomography imaging glucose metabolism and amyloid-β deposition, we tested whether and how life-long changes in glucose metabolism relate to amyloid-β deposition and Alzheimer’s disease-related hypometabolism. Nine healthy young adults (age range: 20–30), 96 cognitively normal older adults (age range: 61–96), and 20 patients with Alzheimer’s disease (age range: 50–90) were scanned using fluorodeoxyglucose and Pittsburgh compound B positron emission tomography. Among cognitively normal older subjects, 32 were further classified as amyloid-positive, with 64 as amyloid-negative. To assess the contribution of glucose metabolism to the regional vulnerability to amyloid-β deposition, we defined the highest and lowest metabolic regions in young adults and examined differences in amyloid deposition between these regions across groups. Two-way analyses of variance were conducted to assess regional differences in age and amyloid-β-related changes in glucose metabolism. Multiple regressions were applied to examine the association between amyloid-β deposition and regional glucose metabolism. Both region of interest and whole-brain voxelwise analyses were conducted to complement and confirm the results derived from the other approach. Regional differences in glucose metabolism between the highest and lowest metabolism regions defined in young adults (T = 12.85, P glucose metabolism regions defined in young adults (T = 2.05, P glucose metabolism were found such that frontal glucose metabolism was reduced with age, while glucose

Epicardial adipose tissue in endocrine and metabolic diseases.

Science.gov (United States)

Iacobellis, Gianluca

2014-05-01

Epicardial adipose tissue has recently emerged as new risk factor and active player in metabolic and cardiovascular diseases. Albeit its physiological and pathological roles are not completely understood, a body of evidence indicates that epicardial adipose tissue is a fat depot with peculiar and unique features. Epicardial fat is able to synthesize, produce, and secrete bioactive molecules which are then transported into the adjacent myocardium through vasocrine and/or paracrine pathways. Based on these evidences, epicardial adipose tissue can be considered an endocrine organ. Epicardial fat is also thought to provide direct heating to the myocardium and protect the heart during unfavorable hemodynamic conditions, such as ischemia or hypoxia. Epicardial fat has been suggested to play an independent role in the development and progression of obesity- and diabetes-related cardiac abnormalities. Clinically, the thickness of epicardial fat can be easily and accurately measured. Epicardial fat thickness can serve as marker of visceral adiposity and visceral fat changes during weight loss interventions and treatments with drugs targeting the fat. The potential of modulating the epicardial fat with targeted pharmacological agents can open new avenues in the pharmacotherapy of endocrine and metabolic diseases. This review article will provide Endocrine's reader with a focus on epicardial adipose tissue in endocrinology. Novel, established, but also speculative findings on epicardial fat will be discussed from the unexplored perspective of both clinical and basic Endocrinologist.

Cerebral glucose metabolism and cognition in newly diagnosed Parkinson's disease: ICICLE-PD study.

Science.gov (United States)

Firbank, M J; Yarnall, A J; Lawson, R A; Duncan, G W; Khoo, T K; Petrides, G S; O'Brien, J T; Barker, R A; Maxwell, R J; Brooks, D J; Burn, D J

2017-04-01

To assess reductions of cerebral glucose metabolism in Parkinson's disease (PD) with 18F-fluorodeoxyglucose (FDG) positron emission tomography (PET), and their associations with cognitive decline. FDG-PET was performed on a cohort of 79 patients with newly diagnosed PD (mean disease duration 8 months) and 20 unrelated controls. PD participants were scanned while on their usual dopaminergic medication. Cognitive testing was performed at baseline, and after 18 months using the Cognitive Drug Research (CDR) and Cambridge Neuropsychological Test Automated Battery (CANTAB) computerised batteries, the Mini-Mental State Examination (MMSE), and the Montreal Cognitive Assessment (MoCA). We used statistical parametric mapping (SPM V.12) software to compare groups and investigate voxelwise correlations between FDG metabolism and cognitive score at baseline. Linear regression was used to evaluate how levels of cortical FDG metabolism were predictive of subsequent cognitive decline rated with the MMSE and MoCA. PD participants showed reduced glucose metabolism in the occipital and inferior parietal lobes relative to controls. Low performance on memory-based tasks was associated with reduced FDG metabolism in posterior parietal and temporal regions, while attentional performance was associated with more frontal deficits. Baseline parietal to cerebellum FDG metabolism ratios predicted MMSE (β=0.38, p=0.001) and MoCA (β=0.3, p=0.002) at 18 months controlling for baseline score. Reductions in cortical FDG metabolism were present in newly diagnosed PD, and correlated with performance on neuropsychological tests. A reduced baseline parietal metabolism is associated with risk of cognitive decline and may represent a potential biomarker for this state and the development of PD dementia. Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://www.bmj.com/company/products-services/rights-and-licensing/.

Lipid metabolism in the heart. Contribution of BMIPP to the diseased heart

Energy Technology Data Exchange (ETDEWEB)

Nohara, Ryuji [Tazuke Kofukai Medical Research Inst., Osaka (Japan). Kitano Hospital

2001-10-01

Lipid contributes greatly in cardiac metabolism to produce high energy ATPs, and is suggested to be related to the progression and deterioration of heart disease. It is fortunate that the I-123-betamethyliodophenylpentadecanoic acid (BMIPP) imaging technique is now available in determining heart condition, but we must be cautious about the interpretation of images obtained with new tracer. From the uptake of BMIPP into the cell to breakdown and catabolism of it, there exist so many critical enzymatical pathways relating to the modification of BMIPP imaging. In clinical evaluation, the image will be translated as the integral effects of these pathways. In order words, we must be aware of these critical pathways regulating lipid metabolism and modifying factors in order to correctly understand BMIPP imaging. Lipid transport is affected by the albumin/FFA ratio in the blood, and extraction with membrane transporter proteins. Fatty acid binding protein (FABP) in the cytosole will play an important role in regulating lipid flux and following metabolism. Lipid will be utilized either for oxidation, triglyceride or phospholipid formation. For oxidation, carnitine palmitoil transferase is the key enzyme for the entrance of lipid into mitochondria, and oxidative enzymes such as acyl CoA dehydrogenase (MCAD, LCAD, HAD) will determine lipid use for the TCA cycle. ATPs produced in the mitochondria again limit the TG store. It is well known that BMIPP imaging completely changes in the ischemic condition, and is also shown that lipid metabolical regulation completely differs from normal in the very early phase of cardiac hypertrophy. In the process of deteriorating heart failure, metabolical switching of lipid with glucose will take place. In such a different heart disease conditions, it is clear that lipid metabolical regulation, including many lipid enzymes, works differently from in the healthy condition. These lipid enzymes are regulated by nuclear factor peroxisome

The significance of adiponectin as a biomarker in metabolic syndrome and/or coronary artery disease.

Science.gov (United States)

Stojanović, Sanja; Ilić, Marina Deijanin; Ilić, Stevan; Petrović, Dejan; Djukić, Svetlana

2015-09-01

BACKGROUND/AIM. Adiponectin exerts profound protective actions during insulin resistence or prediabetes progression towards more severe clinical entities such as metabolic syndrome and/or cardiovascular disease. Since hypoadiponectinaemia contributes to the pathophysiology of the metabolic syndrome and coronary artery disease the level of circulating adiponectin may be an early marker of cardiovascular events. The aim of this study was to determine the relationships between serum adiponectin levels and parameters of both insulin sensitivity and obesity in patients with the metabolic syndrome and/or coronary artery disease, as well as to assess predictive value of adiponectin serum levels as a biomarker of these entitetis. The study included 100 patients with metabolic syndrome and/or coronary artery disease with different degree of insulin resistance and healthy, normoglycemic individuals. The control group comprising healthy, normoglycemic individuals was used for comparison. Serum level of adiponectin, fasting glucose, fasting insulinemia Homeostasis Model Assessment of Insulin Resistance (HOMA-IR) index and anthropometric parameters were determined in all the subjects. Adiponectin was measured by using the ultrasensitive ELISA method. Insulinemia was measured by the radioimmunoassay (RIA) method. The presence of glycemic disorders was assessed on the basis of oral glucose tolerance test (OGTT). Results. Adiponectin level was inversely correlated with age (ρ = -0.015), parameters of both obesity (R = 0.437;p insulin resistance (R = 0.374; p insulin resistance. Most importantly, a statistically significant rapid decrease ih adiponectin was in the prediabetic stages (p < 0.01). The predictor value of adiponectin was 1,356.32 ± 402.65 pg/mL. The obtained resultats suggest that adiponectin may be a useful marker in identification of individuals with risk of developing metabolic syndrome and coronary artery disease, as well as a predictor of prediabetes.

The significance of adiponectin as a biomarker in metabolic syndrome and/or coronary artery disease

Directory of Open Access Journals (Sweden)

Stojanović Sanja

2015-01-01

Full Text Available Introduction/Aim. Adiponectin exerts profound protective actions during insulin resistence or prediabetes progression towards more severe clinical entities such as metabolic syndrome and/or cardiovascular disease. Since hypoadiponectinaemia contributes to the pathophysiology of the metabolic syndrome and coronary artery disease the level of circulating adiponectin may be an early marker of cardiovascular events. The aim of this study was to determine the relationships between serum adiponectin levels and parameters of both insulin sensitivity and obesity in patients with the metabolic syndrome and/or coronary artery disease, as well as to assess predictive value of adiponectin serum levels as a biomarker of these entitetis. Methods. The study included 100 patients with metabolic syndrome and/or coronary artery disease with different degree of insulin resistance and healthy, normoglycemic individuals. The control group comprising healthy, normoglycemic individuals was used for comparison. Serum level of adiponectin, fasting glucose, fasting insulinemia Homeostasis Model Assessment of Insulin Resistance (HOMAIR index and anthropometric parameters were determined in all the subjects. Adiponectin was measured by using the ultrasensitive ELISA method. Insulinemia was measured by the radioimmunoassay (RIA method. The presence of glycemic disorders was assessed on the basis of oral glucose tolerance test (OGTT. Results. Adiponectin level was inversely correlated with age (ρ = - 0.015, parameters of both obesity (R = 0.437; p < 0.001 and insulin resistance (R = 0.374; p < 0.01. Decreasing in the level of adiponectin was strongly implicated in the development of insulin resistance. Most importantly, a statistically significant rapid decrease in adiponectin was in the prediabetic stages (p < 0.01. The predictor value of adiponectin was 1,356.32 ± 402.65 рg/mL. Conclusions. The obtained resultats suggest that adiponectin may be a useful marker in

Dosage effect of a Phex mutation in a murine model of X-linked hypophosphatemia

Science.gov (United States)

Ichikawa, Shoji; Gray, Amie K.; Bikorimana, Emmanuel; Econs, Michael J.

2013-01-01

X-linked hypophosphatemia (XLH) is caused by mutations in the PHEX gene, which increase circulating levels of the phosphaturic hormone, fibroblast growth factor 23 (FGF23). Since XLH is a dominant disease, one mutant allele is sufficient for manifestation of the disease. However, dosage effect of a PHEX mutation in XLH is not completely understood. To examine the effect of Phex genotypes, we compared serum biochemistries and skeletal measures between all five possible genotypes of a new murine model of XLH (PhexK496X or PhexJrt). Compared to sex-matched littermate controls, all Phex mutant mice had hypophosphatemia, mild hypocalcemia, and increased parathyroid hormone and alkaline phosphatase levels. Furthermore, mutant mice had markedly elevated serum Fgf23 levels due to increased Fgf23 expression and reduced cleavage of Fgf23. Although females with a homozygous Phex mutation were slightly more hypocalcemic and hypophosphatemic than heterozygous females, the two groups had comparable intact Fgf23 levels. Similarly, there was no difference in intact Fgf23 or phosphorus concentrations between hemizygous males and heterozygous females. Compared to heterozygous females, homozygous counterparts were significantly smaller and had shorter femurs with reduced bone mineral density, suggesting the existence of dosage effect in the skeletal phenotype of XLH. However, overall phenotypic trends in regards to mineral ion homeostasis were mostly unaffected by the presence of one or two mutant Phex allele(s). The lack of gene dosage effect on circulating Fgf23 (and thus, phosphorus) levels suggests that a Phex mutation may create the lower set point for extracellular phosphate concentrations. PMID:23700148

21 CFR 520.1696 - Penicillin oral dosage forms.

Science.gov (United States)

2010-04-01

... 21 Food and Drugs 6 2010-04-01 2010-04-01 false Penicillin oral dosage forms. 520.1696 Section 520.1696 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED) ANIMAL DRUGS, FEEDS, AND RELATED PRODUCTS ORAL DOSAGE FORM NEW ANIMAL DRUGS § 520.1696 Penicillin oral...

21 CFR 520.45 - Albendazole oral dosage forms.

Science.gov (United States)

2010-04-01

... 21 Food and Drugs 6 2010-04-01 2010-04-01 false Albendazole oral dosage forms. 520.45 Section 520.45 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED) ANIMAL DRUGS, FEEDS, AND RELATED PRODUCTS ORAL DOSAGE FORM NEW ANIMAL DRUGS § 520.45 Albendazole oral...

Metabolic flexibility as an adaptation to energy resources and requirements in health and disease.

Science.gov (United States)

Smith, Reuben L; Soeters, Maarten R; Wüst, Rob C I; Houtkooper, Riekelt H

2018-04-24

The ability to efficiently adapt metabolism by substrate sensing, trafficking, storage and utilization, dependent on availability and requirement is known as metabolic flexibility. In this review, we discuss the breadth and depth of metabolic flexibility and its impact on health and disease. Metabolic flexibility is essential to maintain energy homeostasis in times of either caloric excess or caloric restriction, and in times of either low or high energy demand, such as during exercise. The liver, adipose tissue and muscle govern systemic metabolic flexibility and manage nutrient sensing, uptake, transport, storage and expenditure by communication via endocrine cues. At a molecular level, metabolic flexibility relies on the configuration of metabolic pathways which is regulated by key metabolic enzymes and transcription factors, many of which interact closely with the mitochondria. Disrupted metabolic flexibility, or metabolic inflexibility, however, is associated with many pathological conditions including metabolic syndrome, type 2 diabetes mellitus, and cancer. Multiple factors like dietary composition and feeding frequency, exercise training, and use of pharmacological compounds influence metabolic flexibility and will be discussed here. Lastly, we outline important advances in metabolic flexibility research and discuss medical horizons and translational aspects.

Missing dosages and neuroleptic usage may prolong length of stay in hospitalized Parkinson's disease patients.

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Daniel Martinez-Ramirez

Full Text Available Parkinson's disease patients are more likely to be hospitalized, have higher rates of hospital complications, and have an increased risk of deterioration during hospitalization. Length of stay is an important underlying factor for these increased risks. We aimed to investigate potential medication errors that may occur during hospitalization and its impact on length of hospital stay.A cross-sectional chart review of 339 consecutive hospital encounters from 212 PD subjects was performed. Medication errors were defined as wrong timing or omission of administration for dopaminergic drugs and administration of contraindicated dopamine blockers. An analysis of covariance was applied to examine whether these medication errors were related to increased length of hospital stays.A significant effect for dopaminergic administration (p<0.01 on length of hospital stay was observed. Subjects who had delayed administration or missed at least one dose stayed longer (M=8.2 days, SD=8.9 vs. M=3.6 days SD=3.4. Contraindicated dopamine blocking agents were administered in 23% (71/339 of cases, and this was also significantly related to an increased length of stay (M=8.2 days, SD=8.9 vs. M=3.6 days SD=3.4, p<0.05. Participants who received a contraindicated dopamine blocker stayed in the hospital longer (M=7.5 days, SD=9.1 compared to those who did not (M=5.9 days, SD=6.8. Neurologists were consulted in 24.5% of encounters. Specialty consultation had no effect on the medication related errors.Missing dopaminergic dosages and administration of dopamine blockers occur frequently in hospitalized Parkinson's disease patients and this may impact length of stay. These potentially modifiable factors may reduce the risk of a longer stay related to hospitalization.

Cerebral blood flow and metabolic abnormalities in Alzheimer's disease

Energy Technology Data Exchange (ETDEWEB)

Matsuda, Hiroshi [National Center of Neurology and Psychiatry, Kodaira, Tokyo (Japan). National Center Hospital for Mental, Nervous, and Muscular Disorders

2001-04-01

In this review I summarize observations of PET and SPECT studies about cerebral blood flow and metabolic abnormalities in Alzheimer's disease (AD). In very early AD flow or metabolism reduces first in the posterior cingulate gyrus and precuneus. This reduction may arise from functional deafferentation caused by primary neural degeneration in the remote area of the entorhinal cortex that is the first to be pathologically affected in AD. Then medial temporal structures and parietotemporal association cortex show flow or metabolic reduction as disease processes. The reason why flow or metabolism in medial temporal structures shows delay in starting to reduce in spite of the earliest pathological affection remains to be elucidated. It is likely that anterior cingulate gyrus is functionally involved, since attention is the first non-memory domain to be affected, before deficits in language and visuospatial functions. However few reports have described involvement in the anterior cingulate gyrus. Relationship between cerebral blood flow or metabolism and apolipoprotein E (APOE) genotype has been investigated. Especially, the APOE{epsilon}4 allele has been reported to increase risk and to lower onset age as a function of the inherited dose of the {epsilon}4 allele. Reduction of flow or metabolism in the posterior cingulate gyrus and precuneus has been reported even in presymptomatic nondemented subjects who were cognitively normal and had at least a single {epsilon}4 allele. On the contrary the relation of {epsilon}4 allele to the progression rate of AD has been controversial from neuroimaging approaches. PET and SPECT imaging has become to be quite useful for assessing therapeutical effects of newly introduced treatment for AD. Recent investigations observed significant regional flow increase after donepezil hydrochloride treatment. Most of these observations have been made by applying computer assisted analysis of three-dimensional stereotactic surface projection

Gene dosage, expression, and ontology analysis identifies driver genes in the carcinogenesis and chemoradioresistance of cervical cancer.

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Malin Lando

2009-11-01

Full Text Available Integrative analysis of gene dosage, expression, and ontology (GO data was performed to discover driver genes in the carcinogenesis and chemoradioresistance of cervical cancers. Gene dosage and expression profiles of 102 locally advanced cervical cancers were generated by microarray techniques. Fifty-two of these patients were also analyzed with the Illumina expression method to confirm the gene expression results. An independent cohort of 41 patients was used for validation of gene expressions associated with clinical outcome. Statistical analysis identified 29 recurrent gains and losses and 3 losses (on 3p, 13q, 21q associated with poor outcome after chemoradiotherapy. The intratumor heterogeneity, assessed from the gene dosage profiles, was low for these alterations, showing that they had emerged prior to many other alterations and probably were early events in carcinogenesis. Integration of the alterations with gene expression and GO data identified genes that were regulated by the alterations and revealed five biological processes that were significantly overrepresented among the affected genes: apoptosis, metabolism, macromolecule localization, translation, and transcription. Four genes on 3p (RYBP, GBE1 and 13q (FAM48A, MED4 correlated with outcome at both the gene dosage and expression level and were satisfactorily validated in the independent cohort. These integrated analyses yielded 57 candidate drivers of 24 genetic events, including novel loci responsible for chemoradioresistance. Further mapping of the connections among genetic events, drivers, and biological processes suggested that each individual event stimulates specific processes in carcinogenesis through the coordinated control of multiple genes. The present results may provide novel therapeutic opportunities of both early and advanced stage cervical cancers.

Metabolic profiling of presymptomatic Huntington’s disease sheep reveals novel biomarkers

Science.gov (United States)

Skene, Debra J.; Middleton, Benita; Fraser, Cara K.; Pennings, Jeroen L. A.; Kuchel, Timothy R.; Rudiger, Skye R.; Bawden, C. Simon; Morton, A. Jennifer

2017-01-01

The pronounced cachexia (unexplained wasting) seen in Huntington’s disease (HD) patients suggests that metabolic dysregulation plays a role in HD pathogenesis, although evidence of metabolic abnormalities in HD patients is inconsistent. We performed metabolic profiling of plasma from presymptomatic HD transgenic and control sheep. Metabolites were quantified in sequential plasma samples taken over a 25 h period using a targeted LC/MS metabolomics approach. Significant changes with respect to genotype were observed in 89/130 identified metabolites, including sphingolipids, biogenic amines, amino acids and urea. Citrulline and arginine increased significantly in HD compared to control sheep. Ten other amino acids decreased in presymptomatic HD sheep, including branched chain amino acids (isoleucine, leucine and valine) that have been identified previously as potential biomarkers of HD. Significant increases in urea, arginine, citrulline, asymmetric and symmetric dimethylarginine, alongside decreases in sphingolipids, indicate that both the urea cycle and nitric oxide pathways are dysregulated at early stages in HD. Logistic prediction modelling identified a set of 8 biomarkers that can identify 80% of the presymptomatic HD sheep as transgenic, with 90% confidence. This level of sensitivity, using minimally invasive methods, offers novel opportunities for monitoring disease progression in HD patients. PMID:28223686

Patients with psoriasis have insufficient knowledge of their risk of atherothrombotic disease and metabolic syndrome

DEFF Research Database (Denmark)

Skiveren, J; Philipsen, P; Therming, Gitte

2015-01-01

BACKGROUND: Knowledge is crucial to allow patients to increase their level of self-care. OBJECTIVES: To examine the extent to which patients with moderate to severe psoriasis feel informed about their disease, to investigate their level of knowledge about psoriasis and the associated risk...... to a questionnaire. RESULTS: Patients were well informed about their skin disease, but were less well informed about their risk of atherothrombotic disease/metabolic syndrome (visual analogue scale values of 6.91 and 5.15, respectively). Patients' knowledge of the disease was reflected by 74.2-99.1% correct answers...... (CA). The risk of arthritis elicited 88% CA and of depression 41.7% CA, while the risk of atherothrombotic disease and metabolic syndrome produced only 11.9-15.3% CA. Patients treated with biological drugs had a significantly stronger sense of being more well informed about the risk of disease (P = 0...

Police trauma and cardiovascular disease: association between PTSD symptoms and metabolic syndrome.

Science.gov (United States)

Violanti, John M; Fekedulegn, Desta; Hartley, Tara A; Andrew, Michael E; Charles, Luenda E; Mnatsakanova, Anna; Burchfiel, Cecil M

2006-01-01

Although prior evidence exists concerning the association between posttraumatic stress disorder (PTSD) and cardiovascular disease, few studies have examined associations of PTSD symptomatology and the metabolic syndrome in the high stress occupation of police work. The metabolic syndrome is a clustering of cardiovascular disease risk factors that have also been independently associated with psychological conditions. The aim of this study was to examine associations between the PTSD symptoms and metabolic syndrome in police officers. A stratified sample of 115 police officers was randomly selected from the Buffalo, NY Police Department. PTSD symptoms were measured with the Impact of Event scale (IES), divided into categories of subclinical, mild, moderate and severe symptom levels. The metabolic syndrome was considered present if three or more of its component parameters (obesity, elevated blood pressure, reduced high density lipoprotein (HDL) cholesterol, elevated triglycerides, and abnormal glucose levels) were present in each officer. Results indicated a significantly increased prevalence of the metabolic syndrome among those officers in the severe PTSD symptom category compared with the lowest PTSD severity category (prevalence ratio (PR) = 3.31, 95% C.I. = 1.19 - 9.22). Adjustment for age did not alter the association appreciably (PR = 3.12, 95% C.I. = 1.15 - 8.50). Adjustment for several demographic and lifestyle factors (age, education, smoking, alcohol intake) reduced the magnitude of the prevalence ratio slightly for the severe versus subclinical PTSD category (PR = 2.69, 95% C.I. = 0. 79 - 9.13), with adjustment for age and education accounting for most of the attenuation (PR = 2.71, 95% C.I. = 0.99 - 7.37). Thus, officers with severe PTSD symptoms were approximately three times more likely to have the metabolic syndrome and education may account for some of this association.

Practice Patterns in Screening for Metabolic Disease in Women with PCOS of Diverse Race-Ethnic Backgrounds.

Science.gov (United States)

Mott, Melanie M; Kitos, Nicole R; Coviello, Andrea D

2014-09-01

Women with polycystic ovary syndrome (PCOS) are at high risk for metabolic disorders, which prompted the American Association of Clinical Endocrinologists (AACE) to publish a 2005 position statement recommending screening for metabolic disease.The purposes of the present study were to 1) to examine changes in screening rates for obesity, type 2 diabetes (T2D), metabolic syndrome (MetS), hyperlipidemia (HL), nonalcoholic fatty liver disease (NAFLD), and hypertension (HTN) in women with PCOS after publication of the 2005 AACE position statement and 2) to determine if screening rates and metabolic disorders vary by race-ethnicity. PCOS cases in 2006 (n = 547) and 2011 (n = 1,159) and metabolic disorders were identified by International Classification of Diseases, 9th revision (ICD9) code. Screening rates for metabolic disorders were determined by the presence of blood tests (hemoglobin A1c [HbA1c], lipid profile, alanine aminotransferase/aspartate aminotransferase [ALT/AST]). In 2006, ≤25% of PCOS patients underwent recommended screening tests: HbA1c 18%; lipid profile 11, only HbA1c testing had increased (18% to 21%). Obesity increased from 35% to 40%, while other metabolic disorders remained stable. Black women had the highest rates of obesity and HTN in 2011 (Obesity: Black 48%, Hispanic 44%, White 33%, Other 31%, P1; HTN: Black 18%, Hispanic 9%, White 10%, Other 7%, P1). Blacks and Hispanics were screened more often with ALT/AST testing (Black 27/27%, Hispanic 28/27%, White 23/22%, Other 17/18%, P = .02/.03). Screening rates were higher in the endocrine clinic for all metabolic disorders than in other clinics (P11.

Progranulin: At the interface of neurodegenerative and metabolic diseases

OpenAIRE

Nguyen, Andrew D.; Nguyen, Thi A.; Martens, Lauren Herl; Mitic, Laura L.; Farese, Robert V.

2013-01-01

Progranulin is a widely expressed, cysteine-rich, secreted glycoprotein originally discovered for its growth factor–like properties. Its subsequent identification as a causative gene for frontotemporal dementia (FTD), a devastating early-onset neurodegenerative disease, has catalyzed a surge of new discoveries about progranulin’s function in the brain. More recently, progranulin was recognized as an adipokine involved in diet-induced obesity and insulin resistance, revealing its metabolic fun...

Nutrition and the science of disease prevention: a systems approach to support metabolic health

Science.gov (United States)

Bennett, Brian J.; Hall, Kevin D.; Hu, Frank B.; McCartney, Anne L.; Roberto, Christina

2017-01-01

Progress in nutritional science, genetics, computer science, and behavioral economics can be leveraged to address the challenge of noncommunicable disease. This report highlights the connection between nutrition and the complex science of preventing disease and discusses the promotion of optimal metabolic health, building on input from several complementary disciplines. The discussion focuses on (1) the basic science of optimal metabolic health, including data from gene–diet interactions, microbiome, and epidemiological research in nutrition, with the goal of defining better targets and interventions, and (2) how nutrition, from pharma to lifestyle, can build on systems science to address complex issues. PMID:26415028

Endothelial dysfunction in cardiovascular and endocrine-metabolic diseases: an update

Directory of Open Access Journals (Sweden)

A.P. Davel

2011-09-01

Full Text Available The endothelium plays a vital role in maintaining circulatory homeostasis by the release of relaxing and contracting factors. Any change in this balance may result in a process known as endothelial dysfunction that leads to impaired control of vascular tone and contributes to the pathogenesis of some cardiovascular and endocrine/metabolic diseases. Reduced endothelium-derived nitric oxide (NO bioavailability and increased production of thromboxane A2, prostaglandin H2 and superoxide anion in conductance and resistance arteries are commonly associated with endothelial dysfunction in hypertensive, diabetic and obese animals, resulting in reduced endothelium-dependent vasodilatation and in increased vasoconstrictor responses. In addition, recent studies have demonstrated the role of enhanced overactivation ofβ-adrenergic receptors inducing vascular cytokine production and endothelial NO synthase (eNOS uncoupling that seem to be the mechanisms underlying endothelial dysfunction in hypertension, heart failure and in endocrine-metabolic disorders. However, some adaptive mechanisms can occur in the initial stages of hypertension, such as increased NO production by eNOS. The present review focuses on the role of NO bioavailability, eNOS uncoupling, cyclooxygenase-derived products and pro-inflammatory factors on the endothelial dysfunction that occurs in hypertension, sympathetic hyperactivity, diabetes mellitus, and obesity. These are cardiovascular and endocrine-metabolic diseases of high incidence and mortality around the world, especially in developing countries and endothelial dysfunction contributes to triggering, maintenance and worsening of these pathological situations.

Radioiodine therapy of Graves' disease - a dosimetric comparison of different strategies concerning antithyroid drugs

International Nuclear Information System (INIS)

Urbannek, V.; Voth, E.; Moka, D.; Schicha, H.

2001-01-01

Aim: Premedication with antithyroid drugs (ATD) compared to patients not pretreated with ATD causes a higher failure rate of radioiodine therapy (RITh) or demands higher therapeutical dosage of radioiodine (RI). For clinical reasons and because of accelerated iodine metabolism in hyperthyreosis a compensated thyroid metabolism is desirable. Aim of this study was to investigate the influence of ATD on the biokinetics of RI in case of Graves' disease in order to improve RITh of patients pre-treated with ATD. Methods: 385 consecutive patients who underwent RITh because of Graves' disease for the first time were included: Group A (n = 74): RITh under continuous medication with ATD; Group B (n = 111): Application of RI under continuous medication with ATD, in case of insufficient RI-uptake or shortened effective RI-half-life ATD were stopped 1-5 days after RITh; Group C (n = 200): ATD were stopped 2 days prior to RITh in all patients. We examined the influence of ATD on RI-uptake and effective RI-half-life as well as the absorbed dose achieved on the thyroid in dependence of thyroid volume and applied RI-dosage [TEQ - therapy efficiency quotient, (2)]. Results: In the RI-pretest (all patients under ATD) the RI-uptake was comparable in all three groups. During RITh-RI-uptake, effective RI-half-life and therefore the TEQ were significantly higher in Group C as compared to Groups A and B (p [de

21 CFR 524.1662 - Oxytetracycline hydrochloride ophthalmic and topical dosage forms.

Science.gov (United States)

2010-04-01

... 21 Food and Drugs 6 2010-04-01 2010-04-01 false Oxytetracycline hydrochloride ophthalmic and topical dosage forms. 524.1662 Section 524.1662 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF... DOSAGE FORM NEW ANIMAL DRUGS § 524.1662 Oxytetracycline hydrochloride ophthalmic and topical dosage forms. ...

Association between the dietary factors and metabolic syndrome with chronic kidney disease in Chinese adults

OpenAIRE

Bi, Hui; Wu, Yiqing; Zhao, Chunjie; Long, Gang

2014-01-01

Objective: The aim of study was to examine the relationship between the dietary nutrition and the prevalence and risk of renal damage in patients with metabolic syndrome. Methods: 260 patients with metabolic syndrome and chronic renal disease meeting criterion were recruited in this cross-sectional study. Metabolic syndrome was defined according to NCEP-ATPIII guidelines. Food-frequency questionnaire was performed to collect the information on dietary nutrition. Anthropometric measurements, i...

Metabolism of Cartilage Proteoglycans in Health and Disease

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Demitrios H. Vynios

2014-01-01

Full Text Available Cartilage proteoglycans are extracellular macromolecules with complex structure, composed of a core protein onto which a variable number of glycosaminoglycan chains are attached. Their biosynthesis at the glycosaminoglycan level involves a great number of sugar transferases well-orchestrated in Golgi apparatus. Similarly, their degradation, either extracellular or intracellular in lysosomes, involves a large number of hydrolases. A deficiency or malfunction of any of the enzymes participating in cartilage proteoglycan metabolism may lead to severe disease state. This review summarizes the findings regarding this topic.

The medical food Souvenaid affects brain phospholipid metabolism in mild Alzheimer's disease: results from a randomized controlled trial

OpenAIRE

Rijpma, A.; Graaf, M. van der; Lansbergen, M.M.; Meulenbroek, O.V.; Cetinyurek-Yavuz, A.; Sijben, J.W.; Heerschap, A.; Olde Rikkert, M.G.M.

2017-01-01

Background Synaptic dysfunction contributes to cognitive impairment in Alzheimer?s disease and may be countered by increased intake of nutrients that target brain phospholipid metabolism. In this study, we explored whether the medical food Souvenaid affects brain phospholipid metabolism in patients with Alzheimer?s disease. Methods Thirty-four drug-naive patients with mild Alzheimer?s disease (Mini Mental State Examination score ?20) were enrolled in this exploratory, double-blind, randomized...

Energy Metabolism and Inflammation in Brain Aging and Alzheimer’s Disease

Science.gov (United States)

Yin, Fei; Sancheti, Harsh; Patil, Ishan; Cadenas, Enrique

2016-01-01

The high energy demand of the brain renders it sensitive to changes in energy fuel supply and mitochondrial function. Deficits in glucose availability and mitochondrial function are well-known hallmarks of brain aging and are particularly accentuated in neurodegenerative disorders such as Alzheimer’s disease. As important cellular sources of H2O2, mitochondrial dysfunction is usually associated with altered redox status. Bioenergetic deficits and chronic oxidative stress are both major contributors to cognitive decline associated with brain aging and Alzheimer’s disease. Neuroinflammatory changes, including microglial activation and production of inflammatory cytokines, are observed in neurodegenerative diseases and normal aging. The bioenergetic hypothesis advocates for sequential events from metabolic deficits to propagation of neuronal dysfunction, to aging, and to neurodegeneration, while the inflammatory hypothesis supports microglia activation as the driving force for neuroinflammation. Nevertheless, growing evidence suggests that these diverse mechanisms have redox dysregulation as a common denominator and connector. An independent view of the mechanisms underlying brain aging and neurodegeneration is being replaced by one that entails multiple mechanisms coordinating and interacting with each other. This review focuses on the alterations in energy metabolism and inflammatory responses and their connection via redox regulation in normal brain aging and Alzheimer’s disease. Interactions of these systems is reviewed based on basic research and clinical studies. PMID:27154981

Impact of high cholesterol and endoplasmic reticulum stress on metabolic diseases: An updated mini-review

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Erdi Sozen

2017-08-01

Full Text Available Endoplasmic reticulum (ER is the major site of protein folding and calcium storage. Beside the role of ER in protein homeostasis, it controls the cholesterol production and lipid-membrane biosynthesis as well as surviving and cell death signaling mechanisms in the cell. It is well-documented that elevated plasma cholesterol induces adverse effects in cardiovascular diseases (CVDs, liver disorders, such as non-alcoholic fatty liver disease (NAFLD, non-alcoholic steatosis hepatitis (NASH, and metabolic diseases which are associated with oxidative and ER stress. Recent animal model and human studies have showed high cholesterol and ER stress as an emerging factors involved in the development of many metabolic diseases. In this review, we will summarize the crucial effects of hypercholesterolemia and ER stress response in the pathogenesis of CVDs, NAFLD/NASH, diabetes and obesity which are major health problems in western countries. Keywords: Endoplasmic reticulum stress, High cholesterol, Cardiovascular diseases, Non-alcoholic fatty liver disease, Non-alcoholic steatosis hepatitis

Changes in brain glucose metabolism in subthalamic nucleus deep brain stimulation for advanced Parkinson's disease.

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Volonté, M A; Garibotto, V; Spagnolo, F; Panzacchi, A; Picozzi, P; Franzin, A; Giovannini, E; Leocani, L; Cursi, M; Comi, G; Perani, D

2012-07-01

Despite its large clinical application, our understanding about the mechanisms of action of deep brain stimulation of the subthalamic nucleus is still limited. Aim of the present study was to explore cortical and subcortical metabolic modulations measured by Positron Emission Tomography associated with improved motor manifestations after deep brain stimulation in Parkinson disease, comparing the ON and OFF conditions. Investigations were performed in the stimulator off- and on-conditions in 14 parkinsonian patients and results were compared with a group of matched healthy controls. The results were also used to correlate metabolic changes with the clinical effectiveness of the procedure. The comparisons using Statistical parametric mapping revealed a brain metabolic pattern typical of advanced Parkinson disease. The direct comparison in ON vs OFF condition showed mainly an increased metabolism in subthalamic regions, corresponding to the deep brain stimulation site. A positive correlation exists between neurostimulation clinical effectiveness and metabolic differences in ON and OFF state, including the primary sensorimotor, premotor and parietal cortices, anterior cingulate cortex. Deep brain stimulation seems to operate modulating the neuronal network rather than merely exciting or inhibiting basal ganglia nuclei. Correlations with Parkinson Disease cardinal features suggest that the improvement of specific motor signs associated with deep brain stimulation might be explained by the functional modulation, not only in the target region, but also in surrounding and remote connecting areas, resulting in clinically beneficial effects. Copyright © 2012 Elsevier Ltd. All rights reserved.

Endocrine manifestations related to inherited metabolic diseases in adults

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Vantyghem Marie-Christine

2012-01-01

Full Text Available Abstract Most inborn errors of metabolism (IEM are recessive, genetically transmitted diseases and are classified into 3 main groups according to their mechanisms: cellular intoxication, energy deficiency, and defects of complex molecules. They can be associated with endocrine manifestations, which may be complications from a previously diagnosed IEM of childhood onset. More rarely, endocrinopathies can signal an IEM in adulthood, which should be suspected when an endocrine disorder is associated with multisystemic involvement (neurological, muscular, hepatic features, etc.. IEM can affect all glands, but diabetes mellitus, thyroid dysfunction and hypogonadism are the most frequent disorders. A single IEM can present with multiple endocrine dysfunctions, especially those involving energy deficiency (respiratory chain defects, and metal (hemochromatosis and storage disorders (cystinosis. Non-autoimmune diabetes mellitus, thyroid dysfunction and/or goiter and sometimes hypoparathyroidism should steer the diagnosis towards a respiratory chain defect. Hypogonadotropic hypogonadism is frequent in haemochromatosis (often associated with diabetes, whereas primary hypogonadism is reported in Alström disease and cystinosis (both associated with diabetes, the latter also with thyroid dysfunction and galactosemia. Hypogonadism is also frequent in X-linked adrenoleukodystrophy (with adrenal failure, congenital disorders of glycosylation, and Fabry and glycogen storage diseases (along with thyroid dysfunction in the first 3 and diabetes in the last. This is a new and growing field and is not yet very well recognized in adulthood despite its consequences on growth, bone metabolism and fertility. For this reason, physicians managing adult patients should be aware of these diagnoses.

Cerebral blood flow and oxygen metabolism in patients with Parkinson's disease

International Nuclear Information System (INIS)

Kitamura, Shin; Ujike, Takashi; Kuroki, Soemu; Sakamoto, Shizuki; Soeda, Toshiyuki; Terashi, Akiro; Iio, Masaaki.

1988-01-01

The purpose of this study was to determine functional changes in the cerebral cortex and basal ganglia in Parkinson's disease (PD). Cerebral blood flow (CBF), oxygen extraction fraction (OEF), and cerebral metabolic rate of oxygen (CMRO 2 ) were determined using 0-15 positron emission tomography in 10 PD patients and five age-matched healthy volunteers. There was a tendency among PD patients towards a decreased CBF and CMRO 2 in the cerebral cortex and basal ganglia. These values were significantly lower in the frontal cortex in the PD group than the control group. There was no difference in OEF between the groups. A more decreased cerebral oxygen metabolism was observed in patients staged as severer on the scale of Hoehn and Yahr. There was no correlation between cerebral oxygen metabolism and tremor, rigidity, or bradykinesis. A decreased cerebral oxygen metabolism was associated with mental disorders, such as depression, hallucination, and dementia. These results may provide an important clue for the understanding of mesocortical dopaminergic pathway and the relationship between PD and dementia. (N.K.)

Cerebral blood flow and oxygen metabolism in patients with Parkinson's disease

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Kitamura, Shin; Ujike, Takashi; Kuroki, Soemu; Sakamoto, Shizuki; Soeda, Toshiyuki; Terashi, Akiro; Iio, Masaaki

1988-10-01

The purpose of this study was to determine functional changes in the cerebral cortex and basal ganglia in Parkinson's disease (PD). Cerebral blood flow (CBF), oxygen extraction fraction (OEF), and cerebral metabolic rate of oxygen (CMRO/sub 2/) were determined using 0-15 positron emission tomography in 10 PD patients and five age-matched healthy volunteers. There was a tendency among PD patients towards a decreased CBF and CMRO/sub 2/ in the cerebral cortex and basal ganglia. These values were significantly lower in the frontal cortex in the PD group than the control group. There was no difference in OEF between the groups. A more decreased cerebral oxygen metabolism was observed in patients staged as severer on the scale of Hoehn and Yahr. There was no correlation between cerebral oxygen metabolism and tremor, rigidity, or bradykinesis. A decreased cerebral oxygen metabolism was associated with mental disorders, such as depression, hallucination, and dementia. These results may provide an important clue for the understanding of mesocortical dopaminergic pathway and the relationship between PD and dementia. (N.K.).

21 CFR 522.1222 - Ketamine hydrochloride injectable dosage forms.

Science.gov (United States)

2010-04-01

... 21 Food and Drugs 6 2010-04-01 2010-04-01 false Ketamine hydrochloride injectable dosage forms. 522.1222 Section 522.1222 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN... ANIMAL DRUGS § 522.1222 Ketamine hydrochloride injectable dosage forms. ...

Carotid body, insulin and metabolic diseases: unravelling the links

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Silvia V Conde

2014-10-01

Full Text Available The carotid bodies (CB are peripheral chemoreceptors that sense changes in arterial blood O2, CO2 and pH levels. Hypoxia, hypercapnia and acidosis activate the CB, which respond by increasing the action potential frequency in their sensory nerve, the carotid sinus nerve (CSN. CSN activity is integrated in the brain stem to induce a panoply of cardiorespiratory reflexes aimed, primarily, to normalize the altered blood gases, via hyperventilation, and to regulate blood pressure and cardiac performance, via sympathetic nervous system (SNS activation. Besides its role in the cardiorespiratory control the CB has been proposed as a metabolic sensor implicated in the control of energy homeostasis and, more recently, in the regulation of whole body insulin sensitivity. Hypercaloric diets cause CB overactivation in rats, which seems to be at the origin of the development of insulin resistance and hypertension, core features of metabolic syndrome and type 2 diabetes. Consistent with this notion, CB sensory denervation prevents metabolic and hemodynamic alterations in hypercaloric feed animal. Obstructive sleep apnoea (OSA is another chronic disorder characterized by increased CB activity and intimately related with several metabolic and cardiovascular abnormalities. In this manuscript we review in a concise manner the putative pathways linking CB chemoreceptors deregulation with the pathogenesis of insulin resistance and arterial hypertension. Also, the link between chronic intermittent hypoxia (CIH and insulin resistance is discussed. Then, a final section is devoted to debate strategies to reduce CB activity and its use for prevention and therapeutics of metabolic diseases with an emphasis on new exciting research in the modulation of bioelectronic signals, likely to be central in the future.

Values of iodine metabolism biomarkers in assessing the iodine nutrition status in surgically treated patients with thyroid disease.

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Han, Jian-hua; Wu, Lian; Yu, Song-lin; Fang, Hui-ling; Kamg, Wei-ming; Cheng, Xin-qi; Lu, Jie; Yu, Jian-chun; Qiu, Ling

2015-04-01

To assess the clinical application value of iodine metabolism biomarkers in assessing iodine nutrition status in surgically treated patients with thyroid disease. Blood,morning urine and 24-hour urine samples were collected in 31 healthy volunteers and in 30 surgically treated patients with thyroid disease before and after surgery. Iodine concentration was analyzed by inductively coupled plasma mass spectrometry. The iodine metabolism biomarkers including serum iodine (SI), morning urine iodine(UI), morning urine iodine/urine creatinine ratio (UI/UCr), 24-hour urine iodine (24 h UI), and 24-hour urine iodine excretion (24 h UIE) were evaluated in these two groups. In addition, the validation coincidence rate of iodine metabolism biomarkers in healthy volunteers to different reference ranges including World Health Organization, Mayo Clinic, and Quest Diagnostics were calculated. The UI/UCr ratio of pre-operative thyroid disease patients was significantly lower than that of healthy volunteers (P0.05) between these two groups. The SI, UI ,and 24 h UI in postoperative thyroid disease patients were significantly higher than those of the pre-operative patients (all Piodine metabolism biomarkers. The UI/UCr ratio may be used for iodine nutrition evaluation in surgically treated patients with thyroid disease.

Investigation of contrast agent dosage for perfusion-weighted MRI

International Nuclear Information System (INIS)

Erb, G.; Benner, T.; Heiland, S.; Reith, W.; Sartor, K.; Forsting, M.

1997-01-01

Purpose: In this study we investigated, whether increasing the dosage of a paramagnetic contrast agent results in a stronger signal decrease in T 2 *-weighted perfusion sequences and therefore more meaningful parameter maps. Material and methods: In a prospective study bolus injection of gadolinium-DTPA was performed at dosages of 0.1, 0.2, and 0.3 mmol/kg body weight (BW) in 10 patients each. Before, during and after bolus injection 40 T 2 *-weighted images of a reference brain slice were acquired within 65.6 seconds on a 1.0 T clinical scanner and perfusion parameters were calculated. Results: Due to the limited signal decrease during bolus passage and the resulting low signal-difference-to-noise ratio (ΔS/N) no reliable differentiation of gray and white matter was possible at a contrast agent dosage of 0.1 mmol/kg BW. Only at higher dosages, both, signal decrease and ΔS/N were strong enough to allow differentiation of gray and white matter and to yield reliable parameter maps. Conclusion: For meaningful MR perfusion imaging at 1.0 T and with the given sequence a contrast agent dosage of at least 0.2 mmol/kg BW is necessary, if a 0.5-molar contrast agent is used. (orig.) [de

LITTLE FISH, BIG DATA: ZEBRAFISH AS A MODEL FOR CARDIOVASCULAR AND METABOLIC DISEASE.

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Gut, Philipp; Reischauer, Sven; Stainier, Didier Y R; Arnaout, Rima

2017-07-01

The burden of cardiovascular and metabolic diseases worldwide is staggering. The emergence of systems approaches in biology promises new therapies, faster and cheaper diagnostics, and personalized medicine. However, a profound understanding of pathogenic mechanisms at the cellular and molecular levels remains a fundamental requirement for discovery and therapeutics. Animal models of human disease are cornerstones of drug discovery as they allow identification of novel pharmacological targets by linking gene function with pathogenesis. The zebrafish model has been used for decades to study development and pathophysiology. More than ever, the specific strengths of the zebrafish model make it a prime partner in an age of discovery transformed by big-data approaches to genomics and disease. Zebrafish share a largely conserved physiology and anatomy with mammals. They allow a wide range of genetic manipulations, including the latest genome engineering approaches. They can be bred and studied with remarkable speed, enabling a range of large-scale phenotypic screens. Finally, zebrafish demonstrate an impressive regenerative capacity scientists hope to unlock in humans. Here, we provide a comprehensive guide on applications of zebrafish to investigate cardiovascular and metabolic diseases. We delineate advantages and limitations of zebrafish models of human disease and summarize their most significant contributions to understanding disease progression to date. Copyright © 2017 the American Physiological Society.

Intervention of pumpkin seed oil on metabolic disease revealed by metabonomics and transcript profile.

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Zhao, Xiu-Ju; Chen, Yu-Lian; Fu, Bing; Zhang, Wen; Liu, Zhiguo; Zhuo, Hexian

2017-03-01

Understanding the metabolic and transcription basis of pumpkin seed oil (PSO) intervention on metabolic disease (MD) is essential to daily nutrition and health. This study analyzed the liver metabolic variations of Wistar rats fed normal diet (CON), high-fat diet (HFD) and high-fat plus PSO diet (PSO) to establish the relationship between the liver metabolite composition/transcript profile and the effects of PSO on MD. By using proton nuclear magnetic resonance spectroscopy together with multivariate data analysis, it was found that, compared with CON rats, HFD rats showed clear dysfunctions of choline metabolism, glucose metabolism and nucleotide and amino acid metabolism. Using quantitative real-time polymerase chain reaction (qPCR), it was found that, compared with HFD rats, PSO rats showed alleviated endoplasmic reticulum stress accompanied by lowered unfolded protein response. These findings provide useful information to understand the metabolic alterations triggered by MD and to evaluate the effects of PSO intervention. © 2016 Society of Chemical Industry. © 2016 Society of Chemical Industry.

Aerobic-Strength Exercise Improves Metabolism and Clinical State in Parkinson’s Disease Patients

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Patrik Krumpolec

2017-12-01

Full Text Available Regular exercise ameliorates motor symptoms in Parkinson’s disease (PD. Here, we aimed to provide evidence that exercise brings additional benefits to the whole-body metabolism and skeletal muscle molecular and functional characteristics, which might help to explain exercise-induced improvements in the clinical state. 3-months supervised endurance/strength training was performed in early/mid-stage PD patients and age/gender-matched individuals (n = 11/11. The effects of exercise on resting energy expenditure (REE, glucose metabolism, adiposity, and muscle energy metabolism (31P-MRS were evaluated and compared to non-exercising PD patients. Two muscle biopsies were taken to determine intervention-induced changes in fiber type, mitochondrial content, and expression of genes related to muscle energy metabolism, as well as proliferative and regenerative capacity. Exercise improved the clinical disability score (MDS-UPDRS, bradykinesia, balance, walking speed, REE, and glucose metabolism and increased muscle expression of energy sensors (AMPK. However, the exercise-induced increase in muscle mass/strength, mitochondrial content, type II fiber size, and postexercise phosphocreatine (PCr recovery (31P-MRS were found only in controls. Nevertheless, MDS-UPDRS was associated with muscle AMPK and mechano-growth factor (MGF expression. Improvements in fasting glycemia were positively associated with muscle function and the expression of Sirt1 and Cox7a1, and the parameters of fitness/strength were positively associated with the expression of MyHC2, MyHC7, and MGF. Moreover, reduced bradykinesia was associated with better muscle metabolism (maximal oxidative capacity and postexercise PCr recovery; 31P-MRS. Exercise training improved the clinical state in early/mid-stage Parkinson’s disease patients, including motor functions and whole-body metabolism. Although the adaptive response to exercise in PD was different from that of controls, exercise

The interplay between intestinal bacteria and host metabolism in health and disease: lessons from Drosophila melanogaster

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Adam C. N. Wong

2016-03-01

Full Text Available All higher organisms negotiate a truce with their commensal microbes and battle pathogenic microbes on a daily basis. Much attention has been given to the role of the innate immune system in controlling intestinal microbes and to the strategies used by intestinal microbes to overcome the host immune response. However, it is becoming increasingly clear that the metabolisms of intestinal microbes and their hosts are linked and that this interaction is equally important for host health and well-being. For instance, an individual's array of commensal microbes can influence their predisposition to chronic metabolic diseases such as diabetes and obesity. A better understanding of host–microbe metabolic interactions is important in defining the molecular bases of these disorders and could potentially lead to new therapeutic avenues. Key advances in this area have been made using Drosophila melanogaster. Here, we review studies that have explored the impact of both commensal and pathogenic intestinal microbes on Drosophila carbohydrate and lipid metabolism. These studies have helped to elucidate the metabolites produced by intestinal microbes, the intestinal receptors that sense these metabolites, and the signaling pathways through which these metabolites manipulate host metabolism. Furthermore, they suggest that targeting microbial metabolism could represent an effective therapeutic strategy for human metabolic diseases and intestinal infection.

Dissecting diabetes/metabolic disease mechanisms using pluripotent stem cells and genome editing tools

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Adrian Kee Keong Teo

2015-09-01

Major conclusions: hPSCs and the advancing genome editing tools appear to be a timely and potent combination for probing molecular mechanism(s underlying diseases such as diabetes and metabolic syndromes. The knowledge gained from these hiPSC-based disease modeling studies can potentially be translated into the clinics by guiding clinicians on the appropriate type of medication to use for each condition based on the mechanism of action of the disease.

Fat and Sugar Metabolism During Exercise in Patients With Metabolic Myopathy

Science.gov (United States)

2017-08-31

Metabolism, Inborn Errors; Lipid Metabolism, Inborn Errors; Carbohydrate Metabolism, Inborn Errors; Long-Chain 3-Hydroxyacyl-CoA Dehydrogenase Deficiency; Glycogenin-1 Deficiency (Glycogen Storage Disease Type XV); Carnitine Palmitoyl Transferase 2 Deficiency; VLCAD Deficiency; Medium-chain Acyl-CoA Dehydrogenase Deficiency; Multiple Acyl-CoA Dehydrogenase Deficiency; Carnitine Transporter Deficiency; Neutral Lipid Storage Disease; Glycogen Storage Disease Type II; Glycogen Storage Disease Type III; Glycogen Storage Disease Type IV; Glycogen Storage Disease Type V; Muscle Phosphofructokinase Deficiency; Phosphoglucomutase 1 Deficiency; Phosphoglycerate Mutase Deficiency; Phosphoglycerate Kinase Deficiency; Phosphorylase Kinase Deficiency; Beta Enolase Deficiency; Lactate Dehydrogenase Deficiency; Glycogen Synthase Deficiency

Dietary Omega-3 Fatty Acid Deficiency and High Fructose Intake in the Development of Metabolic Syndrome, Brain Metabolic Abnormalities, and Non-Alcoholic Fatty Liver Disease

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Artemis P. Simopoulos

2013-07-01

Full Text Available Western diets are characterized by both dietary omega-3 fatty acid deficiency and increased fructose intake. The latter found in high amounts in added sugars such as sucrose and high fructose corn syrup (HFCS. Both a low intake of omega-3 fatty acids or a high fructose intake contribute to metabolic syndrome, liver steatosis or non-alcoholic fatty liver disease (NAFLD, promote brain insulin resistance, and increase the vulnerability to cognitive dysfunction. Insulin resistance is the core perturbation of metabolic syndrome. Multiple cognitive domains are affected by metabolic syndrome in adults and in obese adolescents, with volume losses in the hippocampus and frontal lobe, affecting executive function. Fish oil supplementation maintains proper insulin signaling in the brain, ameliorates NAFLD and decreases the risk to metabolic syndrome suggesting that adequate levels of omega-3 fatty acids in the diet can cope with the metabolic challenges imposed by high fructose intake in Western diets which is of major public health importance. This review presents the current status of the mechanisms involved in the development of the metabolic syndrome, brain insulin resistance, and NAFLD a most promising area of research in Nutrition for the prevention of these conditions, chronic diseases, and improvement of Public Health.

Endothelial dysfunction in metabolic diseases: role of oxidation and possible therapeutic employment of N-acetylcysteine.

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Masha, A; Martina, V

2014-01-01

Several metabolic diseases present a high cardiovascular mortality due to endothelial dysfunction consequences. In the last years of the past century, it has come to light that the endothelial cells, previously considered as inert in what regards an eventual secretion activity, play a pivotal role in regulating different aspects of the vascular function (endothelial function). It was clearly demonstrated that the endothelium acts as a real active organ, owning endocrine, paracrine and autocrine modulation activities by means of which it is able to regulate the vascular homeostasis. The present review will investigate the relationship between some metabolic diseases and the endothelial dysfunction and in particular the mechanisms underlying the effects of metabolic pathologies on the endothelium. Furthermore, it will consider the possible therapeutic employment of the N-acetilcysteine in such conditions.

Correlations between abnormal iron metabolism and non-motor symptoms in Parkinson's disease.

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Xu, Wu; Zhi, Yan; Yuan, Yongsheng; Zhang, Bingfeng; Shen, Yuting; Zhang, Hui; Zhang, Kezhong; Xu, Yun

2018-07-01

Despite a growing body of evidence suggests that abnormal iron metabolism plays an important role in the pathogenesis of Parkinson's disease (PD), few studies explored its role in non-motor symptoms (NMS) of PD. The present study aimed to investigate the relationship between abnormal iron metabolism and NMS of PD. Seventy PD patients and 64 healthy controls were consecutively recruited to compare serum iron, ceruloplasmin, ferritin, and transferrin levels. We evaluated five classic NMS, including depression, anxiety, pain, sleep disorder, and autonomic dysfunction in PD patients using the Hamilton Depression Scale (HAMD), the Hamilton Anxiety Scale (HAMA), the short form of the McGill Pain Questionnaire, the Pittsburgh Sleep Quality Index and the Scale for Outcomes in Parkinson's disease for Autonomic Symptoms, respectively. Hierarchical multiple regression analysis was used to investigate the correlations between abnormal iron metabolism and NMS. No differences in serum ceruloplasmin and ferritin levels were examined between PD patients and healthy controls, but we observed significantly decreased serum iron levels and increased serum transferrin levels in PD patients in comparison with healthy controls. After eliminating confounding factors, HAMD scores and HAMA scores were both negatively correlated with serum iron levels and positively correlated with serum transferrin levels. In summary, abnormal iron metabolism might play a crucial role in the pathogenesis of depression and anxiety in PD. Serums levels of iron and transferrin could be peripheral markers for depression and anxiety in PD.

The long noncoding RNA Tug1 connects metabolic changes with kidney disease in podocytes.

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Li, Szu Yuan; Susztak, Katalin

2016-11-01

An increasing amount of evidence suggests that metabolic alterations play a key role in chronic kidney disease (CKD) pathogenesis. In this issue of the JCI, Long et al. report that the long noncoding RNA (lncRNA) taurine-upregulated 1 (Tug1) contributes to CKD development. The authors show that Tug1 regulates mitochondrial function in podocytes by epigenetic targeting of expression of the transcription factor PPARγ coactivator 1α (PGC-1α, encoded by Ppargc1a). Transgenic overexpression of Tug1 specifically in podocytes ameliorated diabetes-induced CKD in mice. Together, these results highlight an important connection between lncRNA-mediated metabolic alterations in podocytes and kidney disease development.

Metabolic imaging using PET

International Nuclear Information System (INIS)

Kudo, Takashi

2007-01-01

There is growing evidence that myocardial metabolism plays a key role not only in ischaemic heart disease but also in a variety of diseases which involve myocardium globally, such as heart failure and diabetes mellitus. Understanding myocardial metabolism in such diseases helps to elucidate the pathophysiology and assists in making therapeutic decisions. As well as providing information on regional changes, PET can deliver quantitative information about both regional and global changes in metabolism. This capability of quantitative measurement is one of the major advantages of PET along with physiological positron tracers, especially relevant in evaluating diseases which involve the whole myocardium. This review discusses major PET tracers for metabolic imaging and their clinical applications and contributions to research regarding ischaemic heart disease and other diseases such as heart failure and diabetic heart disease. Future applications of positron metabolic tracers for the detection of vulnerable plaque are also highlighted briefly. (orig.)

Nonalcoholic Fatty Liver Disease/Non-Alcoholic Steatohepatitis in Childhood: Endocrine-Metabolic “Mal-Programming”

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Manti, Sara; Romano, Claudio; Chirico, Valeria; Filippelli, Martina; Cuppari, Caterina; Loddo, Italia; Salpietro, Carmelo; Arrigo, Teresa

2014-01-01

Context: Nonalcoholic Fatty Liver Disease (NAFLD) is the major chronic liver disease in the pediatric population. NAFLD includes a broad spectrum of abnormalities (inflammation, fibrosis and cirrhosis), ranging from accumulation of fat (also known as steatosis) towards non-alcoholic steatohepatitis (NASH). The development of NAFLD in children is significantly increased. Evidence Acquisition: A literature search of electronic databases was undertaken for the major studies published from 1998 to today. The databases searched were: PubMed, EMBASE, Orphanet, Midline and Cochrane Library. We used the key words: "non-alcoholic fatty liver disease, children, non-alcoholic steatohepatitis and fatty liver". Results: NAFLD/NASH is probably promoted by “multiple parallel hits”: environmental and genetic factors, systemic immunological disorders (oxidative stress, persistent-low grade of inflammation) as well as obesity and metabolic alterations (insulin resistance and metabolic syndrome). However its exact cause still underdiagnosed and unknown. Conclusions: Pediatric NAFLD/NASH is emerging problem. Longitudinal follow-up studies, unfortunately still insufficient, are needed to better understand the natural history and outcome of NAFLD in children. This review focuses on the current knowledge regarding the epidemiology, pathogenesis, environmental, genetic and metabolic factors of disease. The review also highlights the importance of studying the underlying mechanisms of pediatric NAFLD and the need for complete and personalized approach in the management of NAFLD/NASH. PMID:24829591

A role for heme in Alzheimer's disease: Heme binds amyloid β and has altered metabolism

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Atamna, Hani; Frey, William H.

2004-01-01

Heme is a common factor linking several metabolic perturbations in Alzheimer's disease (AD), including iron metabolism, mitochondrial complex IV, heme oxygenase, and bilirubin. Therefore, we determined whether heme metabolism was altered in temporal lobes obtained at autopsy from AD patients and age-matched nondemented subjects. AD brain demonstrated 2.5-fold more heme-b (P < 0.01) and 26% less heme-a (P = 0.16) compared with controls, resulting in a highly significant 2.9-fold decrease in he...

Radiorespirometric study of carbohydrate metabolism in childhood liver disease

International Nuclear Information System (INIS)

DaCosta, H.; Shreeve, W.W.; Merchant, S.

1976-01-01

The need for a suitable parameter to evaluate patients with chronic liver disease has been felt for some time, especially in order to judge the response to surgical shunts and the influence of certain drugs and diets on the liver. Since the liver is a major organ for carbohydrate metabolism, it was decided to analyze the in vivo oxidation of such substrates as glucose and galactose labeled with 14 C. Moderately advanced ''Indian childhood cirrhosis'' and idiopathic fatty hepatic infiltration were selected to represent diffuse chronic liver disease. Oral administration of 14 C-U-glucose or 14 C-1-galactose was followed by analyses of 14 CO 2 in breath by liquid scintillation counting. Conversion of 14 C-glucose to 14 CO 2 was accelerated by both diseases. On the other hand, oxidation of 14 C-galactose was slowed in fatty infiltration and was markedly subnormal in Indian childhood cirrhosis

Regulation of drug-metabolizing enzymes in infectious and inflammatory disease: implications for biologics-small molecule drug interactions.

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Mallick, Pankajini; Taneja, Guncha; Moorthy, Bhagavatula; Ghose, Romi

2017-06-01

Drug-metabolizing enzymes (DMEs) are primarily down-regulated during infectious and inflammatory diseases, leading to disruption in the metabolism of small molecule drugs (smds), which are increasingly being prescribed therapeutically in combination with biologics for a number of chronic diseases. The biologics may exert pro- or anti-inflammatory effect, which may in turn affect the expression/activity of DMEs. Thus, patients with infectious/inflammatory diseases undergoing biologic/smd treatment can have complex changes in DMEs due to combined effects of the disease and treatment. Areas covered: We will discuss clinical biologics-SMD interaction and regulation of DMEs during infection and inflammatory diseases. Mechanistic studies will be discussed and consequences on biologic-small molecule combination therapy on disease outcome due to changes in drug metabolism will be highlighted. Expert opinion: The involvement of immunomodulatory mediators in biologic-SMDs is well known. Regulatory guidelines recommend appropriate in vitro or in vivo assessments for possible interactions. The role of cytokines in biologic-SMDs has been documented. However, the mechanisms of drug-drug interactions is much more complex, and is probably multi-factorial. Studies aimed at understanding the mechanism by which biologics effect the DMEs during inflammation/infection are clinically important.

Bisphenol A sulfonation is impaired in metabolic and liver disease

International Nuclear Information System (INIS)

Yalcin, Emine B.; Kulkarni, Supriya R.; Slitt, Angela L.; King, Roberta

2016-01-01

Background: Bisphenol A (BPA) is a widely used industrial chemical and suspected endocrine disruptor to which humans are ubiquitously exposed. The liver metabolizes and facilitates BPA excretion through glucuronidation and sulfonation. The sulfotransferase enzymes contributing to BPA sulfonation (detected in human and rodents) is poorly understood. Objectives: To determine the impact of metabolic and liver disease on BPA sulfonation in human and mouse livers. Methods: The capacity for BPA sulfonation was determined in human liver samples that were categorized into different stages of metabolic and liver disease (including obesity, diabetes, steatosis, and cirrhosis) and in livers from ob/ob mice. Results: In human liver tissues, BPA sulfonation was substantially lower in livers from subjects with steatosis (23%), diabetes cirrhosis (16%), and cirrhosis (18%), relative to healthy individuals with non-fatty livers (100%). In livers of obese mice (ob/ob), BPA sulfonation was lower (23%) than in livers from lean wild-type controls (100%). In addition to BPA sulfonation activity, Sult1a1 protein expression decreased by 97% in obese mouse livers. Conclusion: Taken together these findings establish a profoundly reduced capacity of BPA elimination via sulfonation in obese or diabetic individuals and in those with fatty or cirrhotic livers versus individuals with healthy livers. - Highlights: • Present study demonstrates that hepatic SULT 1A1/1A3 are primarily sulfonate BPA in mouse and human. • Hepatic BPA sulfonation is profoundly reduced steatosis, diabetes and cirrhosis. • With BPA-S detectable in urine under low or common exposures, these findings are novel and important.

Bisphenol A sulfonation is impaired in metabolic and liver disease

Energy Technology Data Exchange (ETDEWEB)

Yalcin, Emine B.; Kulkarni, Supriya R.; Slitt, Angela L., E-mail: angela_slitt@uri.edu; King, Roberta, E-mail: rking@uri.edu

2016-02-01

Background: Bisphenol A (BPA) is a widely used industrial chemical and suspected endocrine disruptor to which humans are ubiquitously exposed. The liver metabolizes and facilitates BPA excretion through glucuronidation and sulfonation. The sulfotransferase enzymes contributing to BPA sulfonation (detected in human and rodents) is poorly understood. Objectives: To determine the impact of metabolic and liver disease on BPA sulfonation in human and mouse livers. Methods: The capacity for BPA sulfonation was determined in human liver samples that were categorized into different stages of metabolic and liver disease (including obesity, diabetes, steatosis, and cirrhosis) and in livers from ob/ob mice. Results: In human liver tissues, BPA sulfonation was substantially lower in livers from subjects with steatosis (23%), diabetes cirrhosis (16%), and cirrhosis (18%), relative to healthy individuals with non-fatty livers (100%). In livers of obese mice (ob/ob), BPA sulfonation was lower (23%) than in livers from lean wild-type controls (100%). In addition to BPA sulfonation activity, Sult1a1 protein expression decreased by 97% in obese mouse livers. Conclusion: Taken together these findings establish a profoundly reduced capacity of BPA elimination via sulfonation in obese or diabetic individuals and in those with fatty or cirrhotic livers versus individuals with healthy livers. - Highlights: • Present study demonstrates that hepatic SULT 1A1/1A3 are primarily sulfonate BPA in mouse and human. • Hepatic BPA sulfonation is profoundly reduced steatosis, diabetes and cirrhosis. • With BPA-S detectable in urine under low or common exposures, these findings are novel and important.

Peroxisomal β-oxidation regulates whole body metabolism, inflammatory vigor, and pathogenesis of nonalcoholic fatty liver disease

Science.gov (United States)

Moreno-Fernandez, Maria E.; Giles, Daniel A.; Stankiewicz, Traci E.; Sheridan, Rachel; Karns, Rebekah; Cappelletti, Monica; Lampe, Kristin; Mukherjee, Rajib; Sina, Christian; Sallese, Anthony; Bridges, James P.; Hogan, Simon P.; Aronow, Bruce J.; Hoebe, Kasper

2018-01-01

Nonalcoholic fatty liver disease (NAFLD), a metabolic predisposition for development of hepatocellular carcinoma (HCC), represents a disease spectrum ranging from steatosis to steatohepatitis to cirrhosis. Acox1, a rate-limiting enzyme in peroxisomal fatty acid β-oxidation, regulates metabolism, spontaneous hepatic steatosis, and hepatocellular damage over time. However, it is unknown whether Acox1 modulates inflammation relevant to NAFLD pathogenesis or if Acox1-associated metabolic and inflammatory derangements uncover and accelerate potential for NAFLD progression. Here, we show that mice with a point mutation in Acox1 (Acox1Lampe1) exhibited altered cellular metabolism, modified T cell polarization, and exacerbated immune cell inflammatory potential. Further, in context of a brief obesogenic diet stress, NAFLD progression associated with Acox1 mutation resulted in significantly accelerated and exacerbated hepatocellular damage via induction of profound histological changes in hepatocytes, hepatic inflammation, and robust upregulation of gene expression associated with HCC development. Collectively, these data demonstrate that β-oxidation links metabolism and immune responsiveness and that a better understanding of peroxisomal β-oxidation may allow for discovery of mechanisms central for NAFLD progression. PMID:29563328

Dosage of boron traces in graphite, uranium and beryllium oxide; Dosage de traces de bore dans le graphite, l'uranium et l'oxyde de beryllium

Energy Technology Data Exchange (ETDEWEB)

Coursier, J [Ecole Nationale Superieure de Physique et Chimie Industrielles, 75 - Paris (France); Hure, J; Platzer, R [Commissariat a l' Energie Atomique, Saclay (France). Centre d' Etudes Nucleaires

1955-07-01

The problem of the dosage of the boron in the materials serving to the construction of nuclear reactors arises of the following way: to determine to about 0,1 ppm close to the quantities of boron of the order of tenth ppm. We have chosen the colorimetric analysis with curcumin as method of dosage. To reach the indicated contents, it is necessary to do a previous separation of the boron and the materials of basis, either by extraction of tetraphenylarsonium fluoborate in the case of the boron dosage in uranium and the beryllium oxide, either by the use of a cations exchanger resin of in the case of graphite. (M.B.) [French] Le probleme du dosage du bore dans les materiaux servant a la construction de reacteurs nucleaires se pose de la facon suivante: determiner a environ 0,1 ppm pres des quantites de bore de l'ordre de quelques dixiemes de ppm. Nous avons choisit la colorimetrie a la curcumine comme methode de dosage. Pour atteindre les teneurs indiquees, il est necessaire d'effectuer une separation prealable du bore et des materiaux de base, soit par extraction du fluoborate de tetraphenylarsonium dans le cas du dosage de bore dans l'uranium et l'oxyde de beryllium, soit par l'utilisation d'une resine echangeuse de cations dans le cas du graphite. (M.B.)

Dosage compensation of serine-4 transfer RNA in Drosophila melanogaster

International Nuclear Information System (INIS)

Birchler, J.A.; Owenby, R.K.; Jacobson, K.B.

1982-01-01

A dosage series of the X chromosome site for serine-4 transfer RNA consisting of one of three copies in females and one to two in males was constructed to test whether transfer RNA expression is governed by dosage compensation. A dosage effect on the level of the serine-4 isoacceptor was observed in both females and males when the structural locus was varied. However, in males, each dose had a relatively greater expression so the normal one dose was slightly greater than the total female value and the duplicated male had the highest relative expression of all the types examined. Serine-4 levels in males and females from an isogenic Oregon-R stock were similar. Thus the transfer RNA levels conform to the expectations of dosage compensation

Metabolism of 25-hydroxyvitamin D in copper-laden rat: A model of Wilson's disease

International Nuclear Information System (INIS)

Carpenter, T.O.; Pendrak, M.L.; Anast, C.S.

1988-01-01

Wilson's disease results in excess tissue accumulation of copper and is often complicated by skeletal and mineral abnormalities. The authors investigated vitamin D metabolism in rats fed a copper-laden diet rendering hepatic copper content comparable with that found in Wilson's disease. Injection of 25-hydroxyvitamin D 3 [25(OH)D 3 ] resulted in reduced 1,25--dihydroxyvitamin D [1,25(OH) 2 D] levels in copper-intoxicated rats. In vitro 25(OH)D-1α-hydroxylase activity was impaired in renal mitochondria from copper-intoxicated animals. Activity was also inhibited in mitochondrial from controls when copper was added to incubation media. Impaired conversion of 25(OH)D to 1,25(OH) 2 D occurs in copper intoxication and suggests that altered vitamin D metabolism is a potential factor in the development of bone and mineral abnormalities in Wilson's disease

Individual and family strengths: an examination of the relation to disease management and metabolic control in youth with type 1 diabetes.

Science.gov (United States)

Mackey, Eleanor Race; Hilliard, Marisa E; Berger, Sarah Shafer; Streisand, Randi; Chen, Rusan; Holmes, Clarissa

2011-12-01

We examined the association of youths' positive qualities, family cohesion, disease management, and metabolic control in Type 1 diabetes. Two-hundred fifty-seven youth-parent dyads completed the Family Cohesion subscale of the Family Environment Scale, the Diabetes Behavior Rating Scale, 24-hour diabetes interview, and youth completed the Positive Qualities subscale of the Youth Self Report (YSR-PQ). Structural equation modeling demonstrated that YSR-PQ scores were associated with metabolic control mediated by associations with more family cohesion and better disease management. That is, youth with higher YSR-PQ scores had more cohesive families, better disease management, and, indirectly, better metabolic control. Family cohesion was indirectly associated with better metabolic control mediated by its association with better disease management, but not mediated by its association with YSR-PQ scores. Youth who reported more positive qualities, as measured by the YSR-PQ subscale, had better disease management and metabolic control through the association with more family cohesion. However, the current results did not support an alternative hypothesis that cohesive families display better diabetes management mediated by higher YSR-PQ scores.

Metabolic syndrome and the development of vascular disease and type 2 diabetes in high-risk patients

NARCIS (Netherlands)

Wassink, A.M.J.

2009-01-01

Abdominal obesity and its associated insulin resistance play a key role in the clustering of vascular risk factors, known as Metabolic Syndrome. Subjects with Metabolic Syndrome are at increased risk for the development of both type 2 diabetes and cardiovascular disease. Type 2 diabetes and

Magnesium and metabolic syndrome: The role of magnesium in health and disease

Science.gov (United States)

Metabolic syndrome is a constellation of conditions associated with elevated risk of diabetes and cardiovascular disease. Magnesium, the fourth most abundant cation in the human body and required in over 300 enzymatic reactions, has been shown in experimental, observational, and clinical studies to ...

High density lipoprotein cholesterol (HDL) metabolism and its role in ischemic heart disease

International Nuclear Information System (INIS)

Pirzado, Z.A.; Sngi, S.A.; Malik, R.

1999-01-01

Case control and prospective epidemiological studies have found a striking, consistently negative association between High Density Lipoprotein(HDL) levels and coronary vascular events. As a results, the genetic and environmental determinants of HDL levels are being studied intensively. These investigations and their potential clinical applications require a fundamental understanding of the structure, function and metabolism of HDL and its components. Of the special interest are the means by which it exerts its apparently protective effect. In this report we characterize the structure of HLD: and describe its compounds, particularly the protein component. We discuss HDL metabolism in light of the relationship of HDL to other lipoprotein classes and relate what little is known of the functions of HDL. We also review the biochemical mechanism by which HDL may protect against cardiovascular disease and discuss further biochemical research that will be necessary for a better understanding of HDL. Interest in HDL has been greatly intensified in recent years, stimulated largely by the finding that HDL is inversely related in HDL has been greatly intensified in recent years, stimulated largely by the finding that HDL is inversely related to coronary artery disease. Case-control and prospective observations of the striking, consistent and independent negative association between HDL levels and coronary vascular events have in turn generated new interest in the structure, composition and metabolism of these fascinating lipoproteins. Several studies carried out in Pakistan also reveal the inverse relation of HDL to IHD/sup 1,2/. This article contains a tremendous amount of information on HDL and its relationship to genetic and environmental factors which should be useful to investigations and clinicians in their evaluation and use of HDL cholesterol measurements to assess hearth disease risk. A knowledge of the structure, function and metabolism of HDL and its components is

Evolution of vertebrate sex chromosomes and dosage compensation.

Science.gov (United States)

Graves, Jennifer A Marshall

2016-01-01

Differentiated sex chromosomes in mammals and other vertebrates evolved independently but in strikingly similar ways. Vertebrates with differentiated sex chromosomes share the problems of the unequal expression of the genes borne on sex chromosomes, both between the sexes and with respect to autosomes. Dosage compensation of genes on sex chromosomes is surprisingly variable - and can even be absent - in different vertebrate groups. Systems that compensate for different gene dosages include a wide range of global, regional and gene-by-gene processes that differ in their extent and their molecular mechanisms. However, many elements of these control systems are similar across distant phylogenetic divisions and show parallels to other gene silencing systems. These dosage systems cannot be identical by descent but were probably constructed from elements of ancient silencing mechanisms that are ubiquitous among vertebrates and shared throughout eukaryotes.

Fat metabolism during exercise in patients with McArdle disease

DEFF Research Database (Denmark)

Ørngreen, M C; Jeppesen, T D; Andersen, S Tvede

2009-01-01

carbohydrate oxidation was lower, during exercise in patients with McArdle disease vs healthy controls. We found augmented fat oxidation with the onset of a second wind, but further increases in FFA availability, as exercise continued, did not result in further increases in FAO. CONCLUSION: These results......OBJECTIVE: It is known that muscle phosphorylase deficiency restricts carbohydrate utilization, but the implications for muscle fat metabolism have not been studied. We questioned whether patients with McArdle disease can compensate for the blocked muscle glycogen breakdown by enhancing fat...... indicate that patients with McArdle disease have exaggerated fat oxidation during prolonged, low-intensity exercise and that increased fat oxidation may be an important mechanism of the spontaneous second wind. The fact that increasing availability of free fatty acids with more prolonged exercise did...

What fans the fire: insights into mechanisms of leptin in metabolic syndrome-associated heart diseases.

Science.gov (United States)

Dong, Maolong; Ren, Jun

2014-01-01

Obesity and metabolic syndrome are one of the most devastating risk factors for cardiovascular diseases. The obesity gene product leptin plays a central role in the regulation of food intake and energy expenditure. The physiological and pathophysiological roles of leptin in cardiovascular system have been investigated extensively since its discovery in 1994. In addition to its well-established metabolic effects, more recent evidence have depicted a rather pivotal role of leptin in inflammation, oxidative stress, endoplasmic reticulum stress, apoptosis and tissue remodeling en route to the pathogenesis of type 2 diabetes mellitus, hypertension, atherosclerosis, and insulin resistance. Under physiological condition, leptin is known to reduce appetite, promote energy expenditure, increase sympathetic activity, facilitate glucose utilization and improve insulin sensitivity. In addition, leptin may regulate cardiac and vascular function through a nitric oxide-dependent mechanism. However, hyperleptinemia usually occurs with progressively increased body weight and metabolic syndrome development, leading to a state of global or selective leptin resistance. Both central and peripheral leptin resistance may be present under pathophysiological conditions such as inflammation, insulin resistance, hyperlipidemia and a cadre of other cardiovascular diseases including hypertension, atherosclerosis, obesity, ischemic heart disease and heart failure. In this review, we will discuss cardiovascular actions of leptin related to various components of metabolic syndrome. Particular emphasis will be given to insights derived from therapeutic interventions with lifestyle modification, cardiovascular drugs, anti-diabetic and anti-obesity drugs.

Semi-solid dosage form of clonazepam for rapid oral mucosal absorption.

Science.gov (United States)

Sakata, Osamu; Machida, Yoshiharu; Onishi, Hiraku

2011-07-01

In order to obtain an alternative to the intravenous (i.v.) dosage form of clonazepam (CZ), an oral droplet formulation of CZ was developed previously; however, the droplet was physically unstable. Therefore, in the present study, it was attempted to develop an easily-handled dosage form, which was more physically stable and allowed rapid drug absorption from oral mucosa. A semi-solid dosage form, composed of polyethylene glycol 1500 (PEG), CZ, and oleic acid (OA) at 37/1/2 (w/w) and named PEG/CZ/OA, and a semi-solid dosage form containing PEG and CZ at 39/1 (w/w), called PEG/CZ, were prepared. Their physical stability in air at room temperature and oral mucosal absorption in rats were investigated. The semi-solid dosage forms were much more stable physically than the droplet, that is, no recrystallization of CZ was observed for at least 8 days. The effective concentration for humans and rats (20 ng/mL or more) was achieved within 30 min after buccal administration for both PEG/CZ/OA and PEG/CZ. The plasma concentration increased gradually and less varied at each time point for PEG/CZ/OA. PEG/CZ/OA was found to show more rapid and higher absorption of CZ in buccal administration than in sublingual administration. Buccal administration with the semi-solid dosage PEG/CZ with or without OA was suggested to be a possibly useful novel dosage form as an alternative to i.v. injection.

Preparation and characterization of solid oral dosage forms containing soy isoflavones

Directory of Open Access Journals (Sweden)

Stela R. de Oliveira

2013-02-01

Full Text Available Soy isoflavones have been extensively used for menopausal symptoms and prevention of hormone-related cancer, osteoporosis and cardiovascular diseases. Commercially available forms of isoflavones include supplements, capsules and tablets. However, the non-standardization of soy isoflavones extracts and different dissolution profiles of these solid dosage forms highlight the need of additional studies on the development of well characterized pharmaceutical dosage forms of isoflavones. In this work, immediate release oral tablets of soy isoflavones were obtained and evaluated. Genistein and daidzein, were the main constituents of the dried soy extract. Preparation of the tables was accomplished in a rotary tableting machine following either a dry mixture for direct compression or wet granulation with different excipients. Powder, granules and tablets were evaluated for several parameters, including flow properties, Carr and Hausner indexes, hardness, friability, disintegration time and drug release profile. Also, a fast and validated HPLC analytical method for both genistein and daidzein was developed. Formulations containing sodium croscarmellose and sodium dodecyl sulfate resulted in better flowability as indicated by the flow rate and angle of repose, faster disintegration time and immediate release dissolution profile.

Evaluation of insecticides in different dosages to control cicadas in parica plantations

Directory of Open Access Journals (Sweden)

Odineila Martins Monteiro

2014-07-01

Full Text Available This study aimed to determine the more efficient and economically viable dosage of chemical insecticide to control Quesada gigas (Hemiptera: Cicadidae nymphs in parica plantations. Three dosages of three products (carbofuran, imidacloprid and thiamethoxam were tested based on the maximum recommended dosage for the control of cicadas in coffee plants and applied in total area. The dosage of one kilogram of a commercial product based in thiamethoxam per hectare was more efficient economically and environmentally to control nymphs of Q. gigas in parica plantations.

Skeletal muscle metabolism is impaired during exercise in glycogen storage disease type III

DEFF Research Database (Denmark)

Preisler, Nicolai; Laforêt, Pascal; Madsen, Karen Lindhardt

2015-01-01

/kg/min (p = 0.024). Fructose ingestion improved exercise tolerance in the patients. CONCLUSION: Similar to patients with McArdle disease, in whom muscle glycogenolysis is also impaired, GSDIIIa is associated with a reduced skeletal muscle oxidation of carbohydrates and a compensatory increase in fatty acid......OBJECTIVE: Glycogen storage disease type IIIa (GSDIIIa) is classically regarded as a glycogenosis with fixed weakness, but we hypothesized that exercise intolerance in GSDIIIa is related to muscle energy failure and that oral fructose ingestion could improve exercise tolerance in this metabolic...... myopathy. METHODS: We challenged metabolism with cycle-ergometer exercise and measured substrate turnover and oxidation rates using stable isotope methodology and indirect calorimetry in 3 patients and 6 age-matched controls on 1 day, and examined the effect of fructose ingestion on exercise tolerance...

MetSigDis: a manually curated resource for the metabolic signatures of diseases.

Science.gov (United States)

Cheng, Liang; Yang, Haixiu; Zhao, Hengqiang; Pei, Xiaoya; Shi, Hongbo; Sun, Jie; Zhang, Yunpeng; Wang, Zhenzhen; Zhou, Meng

2017-08-22

Complex diseases cannot be understood only on the basis of single gene, single mRNA transcript or single protein but the effect of their collaborations. The combination consequence in molecular level can be captured by the alterations of metabolites. With the rapidly developing of biomedical instruments and analytical platforms, a large number of metabolite signatures of complex diseases were identified and documented in the literature. Biologists' hardship in the face of this large amount of papers recorded metabolic signatures of experiments' results calls for an automated data repository. Therefore, we developed MetSigDis aiming to provide a comprehensive resource of metabolite alterations in various diseases. MetSigDis is freely available at http://www.bio-annotation.cn/MetSigDis/. By reviewing hundreds of publications, we collected 6849 curated relationships between 2420 metabolites and 129 diseases across eight species involving Homo sapiens and model organisms. All of these relationships were used in constructing a metabolite disease network (MDN). This network displayed scale-free characteristics according to the degree distribution (power-law distribution with R2 = 0.909), and the subnetwork of MDN for interesting diseases and their related metabolites can be visualized in the Web. The common alterations of metabolites reflect the metabolic similarity of diseases, which is measured using Jaccard index. We observed that metabolite-based similar diseases are inclined to share semantic associations of Disease Ontology. A human disease network was then built, where a node represents a disease, and an edge indicates similarity of pair-wise diseases. The network validated the observation that linked diseases based on metabolites should have more overlapped genes. © The Author 2017. Published by Oxford University Press. All rights reserved. For Permissions, please email: journals.permissions@oup.com.

Striatal dopamine D2 receptors, metabolism, and volume in preclinical Huntington disease

NARCIS (Netherlands)

van Oostrom, JCH; Maguire, RP; Verschuuren-Bemelmans, CC; van der Duin, LV; Pruim, J; Roos, RAC; Leenders, KL

2005-01-01

Among 27 preclinical carriers of the Huntington disease mutation (PMC), the authors found normal striatal values for MRI volumetry in 88% and for fluorodesoxyglucose PET metabolic index in 67%. Raclopride PET binding potential (RAC-BP) was decreased in 50% and correlated with increases in the

21 CFR 522.1696 - Penicillin G procaine implantation and injectable dosage forms.

Science.gov (United States)

2010-04-01

... 21 Food and Drugs 6 2010-04-01 2010-04-01 false Penicillin G procaine implantation and injectable dosage forms. 522.1696 Section 522.1696 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH... DOSAGE FORM NEW ANIMAL DRUGS § 522.1696 Penicillin G procaine implantation and injectable dosage forms. ...

A Systems Biology Approach Reveals Converging Molecular Mechanisms that Link Different POPs to Common Metabolic Diseases.

Science.gov (United States)

Ruiz, Patricia; Perlina, Ally; Mumtaz, Moiz; Fowler, Bruce A

2016-07-01

A number of epidemiological studies have identified statistical associations between persistent organic pollutants (POPs) and metabolic diseases, but testable hypotheses regarding underlying molecular mechanisms to explain these linkages have not been published. We assessed the underlying mechanisms of POPs that have been associated with metabolic diseases; three well-known POPs [2,3,7,8-tetrachlorodibenzodioxin (TCDD), 2,2´,4,4´,5,5´-hexachlorobiphenyl (PCB 153), and 4,4´-dichlorodiphenyldichloroethylene (p,p´-DDE)] were studied. We used advanced database search tools to delineate testable hypotheses and to guide laboratory-based research studies into underlying mechanisms by which this POP mixture could produce or exacerbate metabolic diseases. For our searches, we used proprietary systems biology software (MetaCore™/MetaDrug™) to conduct advanced search queries for the underlying interactions database, followed by directional network construction to identify common mechanisms for these POPs within two or fewer interaction steps downstream of their primary targets. These common downstream pathways belong to various cytokine and chemokine families with experimentally well-documented causal associations with type 2 diabetes. Our systems biology approach allowed identification of converging pathways leading to activation of common downstream targets. To our knowledge, this is the first study to propose an integrated global set of step-by-step molecular mechanisms for a combination of three common POPs using a systems biology approach, which may link POP exposure to diseases. Experimental evaluation of the proposed pathways may lead to development of predictive biomarkers of the effects of POPs, which could translate into disease prevention and effective clinical treatment strategies. Ruiz P, Perlina A, Mumtaz M, Fowler BA. 2016. A systems biology approach reveals converging molecular mechanisms that link different POPs to common metabolic diseases. Environ

Does canine inflammatory bowel disease influence gut microbial profile and host metabolism?

OpenAIRE

Xu, Jia; Verbrugghe, Adronie; Louren?o, Marta; Janssens, Geert P. J.; Liu, Daisy J. X.; Van de Wiele, Tom; Eeckhaut, Venessa; Van Immerseel, Filip; Van de Maele, Isabel; Niu, Yufeng; Bosch, Guido; Junius, Greet; Wuyts, Brigitte; Hesta, Myriam

2016-01-01

Background Inflammatory bowel disease (IBD) refers to a diverse group of chronic gastrointestinal diseases, and gut microbial dysbiosis has been proposed as a modulating factor in its pathogenesis. Several studies have investigated the gut microbial ecology of dogs with IBD but it is yet unclear if this microbial profile can alter the nutrient metabolism of the host. The aim of the present study was to characterize the faecal bacterial profile and functionality as well as to determine host me...

Physical activity and metabolic disease among people with affective disorders: Prevention, management and implementation.

Science.gov (United States)

Vancampfort, Davy; Stubbs, Brendon

2017-12-15

One in ten and one in three of people with affective disorders experience diabetes and metabolic syndrome respectively. Physical activity (PA) and sedentary behaviour (SB) are key risk factors that can ameliorate the risk of metabolic disease among this population. However, PA is often seen as luxury and/or a secondary component within the management of people with affective disorders. The current article provides a non-systematic best-evidence synthesis of the available literature, detailing a number of suggestions for the implementation of PA into clinical practice. Whilst the evidence is unequivocal for the efficacy of PA to prevent and manage metabolic disease in the general population, it is in its infancy in this patient group. Nonetheless, action must be taken now to ensure that PA and reducing SB are given a priority to prevent and manage metabolic diseases and improve wider health outcomes. PA should be treated as a vital sign and all people with affective disorders asked about their activity levels and if appropriate advised to increase this. There is a need for investment in qualified exercise specialists in clinical practice such as physiotherapists to undertake and oversee PA in practice. Behavioural strategies such as the self-determined theory should be employed to encourage adherence. Funding is required to develop the evidence base and elucidate the optimal intervention characteristics. PA interventions should form an integral part of the multidisciplinary management of people with affective disorders and our article outlines the evidence and strategies to implement this in practice. Copyright © 2016 Elsevier B.V. All rights reserved.

Abnormal metabolism of glycogen phosphate as a cause for Lafora disease.

Science.gov (United States)

Tagliabracci, Vincent S; Girard, Jean Marie; Segvich, Dyann; Meyer, Catalina; Turnbull, Julie; Zhao, Xiaochu; Minassian, Berge A; Depaoli-Roach, Anna A; Roach, Peter J

2008-12-05

Lafora disease is a progressive myoclonus epilepsy with onset in the teenage years followed by neurodegeneration and death within 10 years. A characteristic is the widespread formation of poorly branched, insoluble glycogen-like polymers (polyglucosan) known as Lafora bodies, which accumulate in neurons, muscle, liver, and other tissues. Approximately half of the cases of Lafora disease result from mutations in the EPM2A gene, which encodes laforin, a member of the dual specificity protein phosphatase family that is able to release the small amount of covalent phosphate normally present in glycogen. In studies of Epm2a(-/-) mice that lack laforin, we observed a progressive change in the properties and structure of glycogen that paralleled the formation of Lafora bodies. At three months, glycogen metabolism remained essentially normal, even though the phosphorylation of glycogen has increased 4-fold and causes altered physical properties of the polysaccharide. By 9 months, the glycogen has overaccumulated by 3-fold, has become somewhat more phosphorylated, but, more notably, is now poorly branched, is insoluble in water, and has acquired an abnormal morphology visible by electron microscopy. These glycogen molecules have a tendency to aggregate and can be recovered in the pellet after low speed centrifugation of tissue extracts. The aggregation requires the phosphorylation of glycogen. The aggregrated glycogen sequesters glycogen synthase but not other glycogen metabolizing enzymes. We propose that laforin functions to suppress excessive glycogen phosphorylation and is an essential component of the metabolism of normally structured glycogen.

21 CFR 330.3 - Imprinting of solid oral dosage form drug products.

Science.gov (United States)

2010-04-01

... 21 Food and Drugs 5 2010-04-01 2010-04-01 false Imprinting of solid oral dosage form drug products... AS SAFE AND EFFECTIVE AND NOT MISBRANDED General Provisions § 330.3 Imprinting of solid oral dosage form drug products. A requirement to imprint an identification code on solid oral dosage form drug...

Dietary fatty acids linking postprandial metabolic response and chronic diseases.

Science.gov (United States)

Ortega, Almudena; Varela, Lourdes M; Bermudez, Beatriz; Lopez, Sergio; Abia, Rocio; Muriana, Francisco J G

2012-01-01

Chronic diseases are by far one of the main causes of mortality in the world. One of the current global recommendations to counteract disability and premature death resulting from chronic diseases is to decrease the consumption of energy-dense high-fat diets, particularly those rich in saturated fatty acids (SFA). The most effective replacement for SFA in terms of risk factor outcomes for chronic disease are polyunsaturated fatty acids (PUFA) and monounsaturated fatty acids (MUFA). The biochemical basis for healthy benefits of such a dietary pattern has been widely evaluated under fasting conditions. However, the increasing amount of data available from multiple studies suggest that the postprandial state, i.e., "the period that comprises and follows a meal", plays an important, yet underappreciated, role in the genesis of numerous pathological conditions. In this review, the potential of MUFA, PUFA, and SFA to postprandially affect selected metabolic abnormalities related to chronic diseases is discussed.

Identification of altered metabolic pathways in plasma and CSF in mild cognitive impairment and Alzheimer's disease using metabolomics.

Directory of Open Access Journals (Sweden)

Eugenia Trushina

Full Text Available Alzheimer's Disease (AD currently affects more than 5 million Americans, with numbers expected to grow dramatically as the population ages. The pathophysiological changes in AD patients begin decades before the onset of dementia, highlighting the urgent need for the development of early diagnostic methods. Compelling data demonstrate that increased levels of amyloid-beta compromise multiple cellular pathways; thus, the investigation of changes in various cellular networks is essential to advance our understanding of early disease mechanisms and to identify novel therapeutic targets. We applied a liquid chromatography/mass spectrometry-based non-targeted metabolomics approach to determine global metabolic changes in plasma and cerebrospinal fluid (CSF from the same individuals with different AD severity. Metabolic profiling detected a total of significantly altered 342 plasma and 351 CSF metabolites, of which 22% were identified. Based on the changes of >150 metabolites, we found 23 altered canonical pathways in plasma and 20 in CSF in mild cognitive impairment (MCI vs. cognitively normal (CN individuals with a false discovery rate <0.05. The number of affected pathways increased with disease severity in both fluids. Lysine metabolism in plasma and the Krebs cycle in CSF were significantly affected in MCI vs. CN. Cholesterol and sphingolipids transport was altered in both CSF and plasma of AD vs. CN. Other 30 canonical pathways significantly disturbed in MCI and AD patients included energy metabolism, Krebs cycle, mitochondrial function, neurotransmitter and amino acid metabolism, and lipid biosynthesis. Pathways in plasma that discriminated between all groups included polyamine, lysine, tryptophan metabolism, and aminoacyl-tRNA biosynthesis; and in CSF involved cortisone and prostaglandin 2 biosynthesis and metabolism. Our data suggest metabolomics could advance our understanding of the early disease mechanisms shared in progression from CN to

Automatic identification and normalization of dosage forms in drug monographs

Science.gov (United States)

2012-01-01

Background Each day, millions of health consumers seek drug-related information on the Web. Despite some efforts in linking related resources, drug information is largely scattered in a wide variety of websites of different quality and credibility. Methods As a step toward providing users with integrated access to multiple trustworthy drug resources, we aim to develop a method capable of identifying drug's dosage form information in addition to drug name recognition. We developed rules and patterns for identifying dosage forms from different sections of full-text drug monographs, and subsequently normalized them to standardized RxNorm dosage forms. Results Our method represents a significant improvement compared with a baseline lookup approach, achieving overall macro-averaged Precision of 80%, Recall of 98%, and F-Measure of 85%. Conclusions We successfully developed an automatic approach for drug dosage form identification, which is critical for building links between different drug-related resources. PMID:22336431

Evaluation of the effect of torsemide on warfarin dosage requirements.

Science.gov (United States)

Lai, Sophia; Momper, Jeremiah D; Yam, Felix K

2017-08-01

Background According to drug interaction databases, torsemide may potentiate the effects of warfarin. Evidence for this drug-drug interaction, however, is conflicting and the clinical significance is unknown. Objective The aim of this study is to evaluate the impact of torsemide initiation on warfarin dosage requirements. Setting This study was conducted at the Veterans Affairs Healthcare System in San Diego, California. Method A retrospective cohort study was conducted using Veterans Affairs data from patients who were converted from bumetanide to torsemide between March 2014 and July 2014. Patients were also prescribed and taking warfarin during the observation period. Warfarin dosage requirements were evaluated to determine if any changes occurred within the first 3 months of starting torsemide. Main outcome measure The primary outcome was the average weekly warfarin dose before and after torsemide initiation. Results Eighteen patients met study inclusion criteria. The weekly warfarin dose before and after initiation of torsemide was not significantly different (34 ± 15 and 34 ± 13 mg, p > 0.05). Of those eighteen patients, only two experienced elevations in INR that required a decrease in warfarin dosage after torsemide initiation. Between those two patients, dosage reductions ranged from 5.3 to 18%. Conclusion These results indicated that most patients did not require any warfarin dosage adjustments after torsemide was initiated. The potential for interaction, however, still exists. While empiric warfarin dosage adjustments are not recommended when initiating torsemide, increased monitoring is warranted to minimize the risk of adverse effects.

An observational study on the association of nonalcoholic fatty liver disease and metabolic syndrome with gall stone disease requiring cholecystectomy.

Science.gov (United States)

Ahmed, Farah; Baloch, Qamaruddin; Memon, Zahid Ali; Ali, Iqra

2017-05-01

Recognition of Non alcoholic fatty liver disease (NAFLD) and metabolic syndrome in patients with gallstones undergoing laparoscopic or open cholecystectomy, along with it we will also study the life style of patients with gall stones. Patients with gallstones have associated NAFLD, with concurrent metabolic syndrome and these ailments share similar factors for example obesity, hypertriglyceridemia and diabetes mellitus. Factors like body mass index, gender, raised lipid levels, use of contraceptives and alcohol and having diabetes, physical inactiveness, multiparous women, water with excessive iron content, metabolic syndrome, and NAFLD are accountable factors for gallstones formation. This was a case series done at Surgical Unit 1 of Civil Hospital Karachi. Selective samples of 88 patients were included. Duration was 3 months. We included both sexes with ultrasound proof of gall stone irrespective of cholecystitis. Excluded patients with history of seropositive viral hepatitis, autoimmune and wilson's disease. As these conditions can act as a confounder to our variables. Nafld was present in 62.5%(n = 55) while 28.4% (n = 25) had metabolic syndrome. 26.94% had BMI less than 18, 32.12 had BMI between 18 and 25 and majority had BMI greater than 25 i.e in 40.93%. Of all 46.6% had a family history of cholelithiasis. Gallstone patients with NAFLD reported about their first degree relative being suffering from cholelithiasis at a significant p-value of 0.034 while this was not significant in cases of metabolic syndrome and the p -value was 0.190. We found association of metabolic syndrome with gallstones and NAFLD. Non alcoholic fatty liver was highly prevalent in our study subjects. Huge percentage of first degree relatives of gall stone patients had gallstones and this relation was more pronounced patients who had associated NAFLD.

An Official American Thoracic Society Workshop Report: Obesity and Metabolism. An Emerging Frontier in Lung Health and Disease.

Science.gov (United States)

Suratt, Benjamin T; Ubags, Niki D J; Rastogi, Deepa; Tantisira, Kelan G; Marsland, Benjamin J; Petrache, Irina; Allen, Janice B; Bates, Jason H T; Holguin, Fernando; McCormack, Meredith C; Michelakis, Evangelos D; Black, Stephen M; Jain, Manu; Mora, Ana L; Natarajan, Viswanathan; Miller, Yury I; Fessler, Michael B; Birukov, Konstantin G; Summer, Ross S; Shore, Stephanie A; Dixon, Anne E

2017-06-01

The world is in the midst of an unprecedented epidemic of obesity. This epidemic has changed the presentation and etiology of common diseases. For example, steatohepatitis, directly attributable to obesity, is now the most common cause of cirrhosis in the United States. Type 2 diabetes is increasingly being diagnosed in children. Pulmonary researchers and clinicians are just beginning to appreciate the impact of obesity and altered metabolism on common pulmonary diseases. Obesity has recently been identified as a major risk factor for the development of asthma and for acute respiratory distress syndrome. Obesity is associated with profound changes in pulmonary physiology, the development of pulmonary hypertension, sleep-disordered breathing, and altered susceptibility to pulmonary infection. In short, obesity is leading to dramatic changes in lung health and disease. Simultaneously, the rapidly developing field of metabolism, including mitochondrial function, is shifting the paradigms by which the pathophysiology of many pulmonary diseases is understood. Altered metabolism can lead to profound changes in both innate and adaptive immunity, as well as the function of structural cells. To address this emerging field, a 3-day meeting on obesity, metabolism, and lung disease was convened in October 2015 to discuss recent findings, foster research initiatives, and ultimately guide clinical care. The major findings arising from this meeting are reported in this document.

Evidence for oral agmatine sulfate safety--a 95-day high dosage pilot study with rats.

Science.gov (United States)

Gilad, Gad M; Gilad, Varda H

2013-12-01

Agmatine, decarboxylated arginine, exerts beneficial effects in various experimental disease models. Clinical trials indicate the safety and effectiveness of short-term (up to 21 days) high dose regimens of oral agmatine sulfate, but longer term studies are lacking. This pilot study undertook to assess the safety of a longer term high dosage oral agmatine sulfate in laboratory rats. Adult Wistar rats consumed 5.3 g/l agmatine sulfate in their drinking water for 95 days, a regimen estimated to result in a daily dosage of absorbed agmatine of about 100mg/kg. Animals' body weight, water consumption and blood pressure were periodically measured, and general cage behavior, fur appearance, urination and feces appearance monitored. These parameters were also determined at 20 days after treatment cessation (day 115). On days 95 and 115, animals were euthanized for gross necropsy assessment. Agmatine-treated rats showed slight, but significant reductions in body weight and blood pressure, and reduced water consumption during treatment, which recovered completely within 20 days after treatment cessation. Otherwise, no abnormal behaviors or organ pathologies were observed. These findings are first to suggest apparent safety of sub-chronic high dosage dietary agmatine sulfate in laboratory rats, thus lending further support to the therapeutic applications of agmatine. Copyright © 2013 Elsevier Ltd. All rights reserved.

A computer model simulating human glucose absorption and metabolism in health and metabolic disease states [version 1; referees: 2 approved, 1 approved with reservations

Directory of Open Access Journals (Sweden)

Richard J. Naftalin

2016-04-01

Full Text Available A computer model designed to simulate integrated glucose-dependent changes in splanchnic blood flow with small intestinal glucose absorption, hormonal and incretin circulation and hepatic and systemic metabolism in health and metabolic diseases e.g. non-alcoholic fatty liver disease, (NAFLD, non-alcoholic steatohepatitis, (NASH and type 2 diabetes mellitus, (T2DM demonstrates how when glucagon-like peptide-1, (GLP-1 is synchronously released into the splanchnic blood during intestinal glucose absorption, it stimulates superior mesenteric arterial (SMA blood flow and by increasing passive intestinal glucose absorption, harmonizes absorption with its distribution and metabolism. GLP-1 also synergises insulin-dependent net hepatic glucose uptake (NHGU. When GLP-1 secretion is deficient post-prandial SMA blood flow is not increased and as NHGU is also reduced, hyperglycaemia follows. Portal venous glucose concentration is also raised, thereby retarding the passive component of intestinal glucose absorption.   Increased pre-hepatic sinusoidal resistance combined with portal hypertension leading to opening of intrahepatic portosystemic collateral vessels are NASH-related mechanical defects that alter the balance between splanchnic and systemic distributions of glucose, hormones and incretins.The model reveals the latent contribution of portosystemic shunting in development of metabolic disease. This diverts splanchnic blood content away from the hepatic sinuses to the systemic circulation, particularly during the glucose absorptive phase of digestion, resulting in inappropriate increases in insulin-dependent systemic glucose metabolism.  This hastens onset of hypoglycaemia and thence hyperglucagonaemia. The model reveals that low rates of GLP-1 secretion, frequently associated with T2DM and NASH, may be also be caused by splanchnic hypoglycaemia, rather than to intrinsic loss of incretin secretory capacity. These findings may have therapeutic

NAD(+) metabolism: A therapeutic target for age-related metabolic disease

NARCIS (Netherlands)

Mouchiroud, Laurent; Houtkooper, Riekelt H.; Auwerx, Johan

2013-01-01

Abstract Nicotinamide adenine dinucleotide (NAD) is a central metabolic cofactor by virtue of its redox capacity, and as such regulates a wealth of metabolic transformations. However, the identification of the longevity protein silent regulator 2 (Sir2), the founding member of the sirtuin protein

Application of DBNPA dosage for biofouling control in spiral wound membrane systems

KAUST Repository

Siddiqui, Amber

2017-05-30

Biocides may be used to control biofouling in spiral-wound reverse osmosis (RO) and nanofiltration (NF) systems. The objective of this study was to investigate the effect of biocide 2,2-dibromo-3-ni-trilopropionamide (DBNPA) dosage on biofouling control. Preventive biofouling control was studied applying a continuous dosage of substrate (0.5 mg/L) and DBNPA (1 mg/L). Curative biofouling control was studied on pre-grown biofilms, once again applying a continuous dosage of substrate (0.5 mg acetate C/L) and DBNPA (1 and 20 mg/L). Biofouling studies were performed in membrane fouling simulators (MFSs) supplied with biodegradable substrate and DBNPA. The pressure drop was monitored in time and at the end of the study, the accumulated biomass in MFS was quantified by adenosine triphosphate (ATP) and total organic carbon (TOC) analysis. Continuous dosage of DBNPA (1 mg/L) prevented pressure drop increase and biofilm accumulation in the MFSs during a run time of 7 d, showing that biofouling can be managed by preventive DBNPA dosage. For biofouled systems, continuous dosage of DBNPA (1 and 20 mg/L) inactivated the accumulated biomass but did not restore the original pressure drop and did not remove the accumulated inactive cells and extracellular polymeric substances (EPS), indicating DBNPA dosage is not suitable for curative biofouling control.

Quality of 'Climax' blueberries after low dosage electron beam irradiation

International Nuclear Information System (INIS)

Miller, W.R.; McDonald, R.E.; McCollum, T.G.; Smittle, B.J.

1994-01-01

Fruit of 'Climax' rabbiteye blueberries (Vaccinium ashei Reade) were irradiated by a linear accelerator at 0, 0.25, 0.5, 0.75, 1.0, and 1.25 kGy and evaluated for various quality attributes after storage for 1, 3, 7, or 14 days at 1C plus 2 days at 15C, respectively. Weight loss increased during storage and averaged 4.2% after the final inspection and was not affected by irradiation dosage. About 5% of total berries were decayed after 14 days at 1C, about 6% after the final inspection at 15C, but decay was not affected by the level of irradiation. Electrolyte leakage, skin color, total soluble solids, acidity, and pH were also not affected by irradiation dosage. There was a significant decline in berry firmness, flavor, and texture as dosage increased. Berries treated at 1.0 kGy or above were softer and had lower flavor and texture preference scores than berries treated at lower dosages or nontreated berries

TOR, the Gateway to Cellular Metabolism, Cell Growth, and Disease.

Science.gov (United States)

Blenis, John

2017-09-21

Michael N. Hall is this year's recipient of the Lasker Basic Medical Research Award for the identification of the target of rapamycin, TOR. TOR is a master regulator of the cell's growth and metabolic state, and its dysregulation contributes to a variety of diseases, including diabetes, obesity, neurodegenerative disorders, aging, and cancer, making the TOR pathway an attractive therapeutic target. Copyright © 2017 The Author(s). Published by Elsevier Inc. All rights reserved.

Association Between Motor Symptoms and Brain Metabolism in Early Huntington Disease.

Science.gov (United States)

Gaura, Véronique; Lavisse, Sonia; Payoux, Pierre; Goldman, Serge; Verny, Christophe; Krystkowiak, Pierre; Damier, Philippe; Supiot, Frédéric; Bachoud-Levi, Anne-Catherine; Remy, Philippe

2017-09-01

Brain hypometabolism is associated with the clinical consequences of the degenerative process, but little is known about regional hypermetabolism, sometimes observed in the brain of patients with clinically manifest Huntington disease (HD). Studying the role of regional hypermetabolism is needed to better understand its interaction with the motor symptoms of the disease. To investigate the association between brain hypometabolism and hypermetabolism with motor scores of patients with early HD. This study started in 2001, and analysis was completed in 2016. Sixty symptomatic patients with HD and 15 healthy age-matched control individuals underwent positron emission tomography to measure cerebral metabolism in this cross-sectional study. They also underwent the Unified Huntington's Disease Rating Scale motor test, and 2 subscores were extracted: (1) a hyperkinetic score, combining dystonia and chorea, and (2) a hypokinetic score, combining bradykinesia and rigidity. Statistical parametric mapping software (SPM5) was used to identify all hypo- and hypermetabolic regions in patients with HD relative to control individuals. Correlation analyses (P motor subscores and brain metabolic values were performed for regions with significant hypometabolism and hypermetabolism. Among 60 patients with HD, 22 were women (36.7%), and the mean (SD) age was 44.6 (7.6) years. Of the 15 control individuals, 7 were women (46.7%), and the mean (SD) age was 42.2 (7.3) years. In statistical parametric mapping, striatal hypometabolism was significantly correlated with the severity of all motor scores. Hypermetabolism was negatively correlated only with hypokinetic scores in the cuneus (z score = 3.95, P motor scores were associated with higher metabolic values in the inferior parietal lobule, anterior cingulate, inferior temporal lobule, the dentate nucleus, and the cerebellar lobules IV/V, VI, and VIII bilaterally corresponding to the motor regions of the cerebellum (z score = 3

Intermittent fasting protects against the deterioration of cognitive function, energy metabolism and dyslipidemia in Alzheimer's disease-induced estrogen deficient rats.

Science.gov (United States)

Shin, Bae Kun; Kang, Suna; Kim, Da Sol; Park, Sunmin

2018-02-01

Intermittent fasting may be an effective intervention to protect against age-related metabolic disturbances, although it is still controversial. Here, we investigated the effect of intermittent fasting on the deterioration of the metabolism and cognitive functions in rats with estrogen deficiency and its mechanism was also explored. Ovariectomized rats were infused with β-amyloid (25-35; Alzheimer's disease) or β-amyloid (35-25, Non-Alzheimer's disease; normal cognitive function) into the hippocampus. Each group was randomly divided into two sub-groups: one with intermittent fasting and the other fed ad libitum: Alzheimer's disease-ad libitum, Alzheimer's disease-intermittent fasting, Non-Alzheimer's disease-ad libitum, and Non-Alzheimer's disease-intermittent fasting. Rats in the intermittent fasting groups had a restriction of food consumption to a 3-h period every day. Each group included 10 rats and all rats fed a high-fat diet for four weeks. Interestingly, Alzheimer's disease increased tail skin temperature more than Non-Alzheimer's disease and intermittent fasting prevented the increase. Alzheimer's disease reduced bone mineral density in the spine and femur compared to the Non-Alzheimer's disease, whereas bone mineral density in the hip and leg was reduced by intermittent fasting. Fat mass only in the abdomen was decreased by intermittent fasting. Intermittent fasting decreased food intake without changing energy expenditure. Alzheimer's disease increased glucose oxidation, whereas intermittent fasting elevated fat oxidation as a fuel source. Alzheimer's disease and intermittent fasting deteriorated insulin resistance in the fasting state but intermittent fasting decreased serum glucose levels after oral glucose challenge by increasing insulin secretion. Alzheimer's disease deteriorated short and spatial memory function compared to the Non-Alzheimer's disease, whereas intermittent fasting prevented memory loss in comparison to ad libitum. Unexpectedly

Genetic Variants of Homocysteine Metabolizing Enzymes and the Risk of Coronary Artery Disease

Czech Academy of Sciences Publication Activity Database

Janošíková, B.; Pavlíková, Markéta; Kocmanová, Dora; Vítová, D.; Veselá, K.; Krupková, L.; Kahleová, R.; Krijt, J.; Kraml, P.; Hyánek, J.; Zvárová, Jana; Anděl, M.; Kožich, V.

2003-01-01

Roč. 79, - (2003), s. 167-175 ISSN 1096-7192 R&D Projects: GA MZd NM26; GA MZd NM6548 Keywords : coronary disease * risk factors * genes * homocysteine * metabolism Subject RIV: BB - Applied Statistics, Operational Research Impact factor: 2.038, year: 2003

Chemical Hybridization of Glucagon and Thyroid Hormone Optimizes Therapeutic Impact for Metabolic Disease

DEFF Research Database (Denmark)

Finan, Brian; Clemmensen, Christoffer; Zhu, Zhimeng

2016-01-01

Glucagon and thyroid hormone (T3) exhibit therapeutic potential for metabolic disease but also exhibit undesired effects. We achieved synergistic effects of these two hormones and mitigation of their adverse effects by engineering chemical conjugates enabling delivery of both activities within on...

Metabolically Healthy Obesity and Ischemic Heart Disease

DEFF Research Database (Denmark)

Hansen, Louise; Netterstrom, Marie K.; Johansen, Nanna B.

2017-01-01

Context: Recent studies have suggested that a subgroup of obese individuals is not at increased risk of obesity-related complications. This subgroup has been referred to as metabolically healthy obese. Objective: To investigate whether obesity is a risk factor for development of ischemic heart...... risk factors (low high-density lipoprotein cholesterol, elevated blood pressure, triglycerides, and fasting plasma glucose). Metabolically healthy individuals were defined as having no metabolic risk factors, and metabolically unhealthy individuals were defined as having a minimum of one. Main Outcome...... Measures: IHD. Results: During follow-up, 323 participants developed IHD. Metabolically healthy obese men had increased risk of IHD compared with metabolically healthy normal-weight men [hazard ratio (HR), 3.1; 95% confidence interval (CI), 1.1 to 8.2)]. The corresponding results for women were less...

Preparation and evaluation of doxycycline hydrochloride and bromhexine hydrochloride dosage forms for pigeons / Marga le Roux

OpenAIRE

Le Roux, Marga

2004-01-01

Objective: To prepare and evaluate three different dosage forms, containing doxycycline hydrochloride (HCI) and bromhexine hydrochloride (HCI) respectively and in combination, for the treatment of respiratory diseases in pigeons. Background: Birds have held a place in man's affection since the ancient Egyptians and Romans kept birds. Europeans have successfully bred birds, especially smaller birds and pigeons, for centuries. Only in recent years, however, have science and me...

The medical food Souvenaid affects brain phospholipid metabolism in mild Alzheimer's disease: results from a randomized controlled trial

NARCIS (Netherlands)

Rijpma, A.; Graaf, M. van der; Lansbergen, M.M.; Meulenbroek, O.V.; Cetinyurek-Yavuz, A.; Sijben, J.W.; Heerschap, A.; Olde Rikkert, M.G.M.

2017-01-01

BACKGROUND: Synaptic dysfunction contributes to cognitive impairment in Alzheimer's disease and may be countered by increased intake of nutrients that target brain phospholipid metabolism. In this study, we explored whether the medical food Souvenaid affects brain phospholipid metabolism in patients

Dosage compensation and demasculinization of X chromosomes in Drosophila.

Science.gov (United States)

Bachtrog, Doris; Toda, Nicholas R T; Lockton, Steven

2010-08-24

The X chromosome of Drosophila shows a deficiency of genes with male-biased expression, whereas mammalian X chromosomes are enriched for spermatogenesis genes expressed premeiosis and multicopy testis genes. Meiotic X-inactivation and sexual antagonism can only partly account for these patterns. Here, we show that dosage compensation (DC) in Drosophila may contribute substantially to the depletion of male genes on the X. To equalize expression between X-linked and autosomal genes in the two sexes, male Drosophila hypertranscribe their single X, whereas female mammals silence one of their two X chromosomes. We combine fine-scale mapping data of dosage compensated regions with genome-wide expression profiles and show that most male-biased genes on the D. melanogaster X are located outside dosage compensated regions. Additionally, X-linked genes that have newly acquired male-biased expression in D. melanogaster are less likely to be dosage compensated, and parental X-linked genes that gave rise to an autosomal male-biased retrocopy are more likely located within compensated regions. This suggests that DC contributes to the observed demasculinization of X chromosomes in Drosophila, both by limiting the emergence of male-biased expression patterns of existing X genes, and by contributing to gene trafficking of male genes off the X. Copyright 2010 Elsevier Ltd. All rights reserved.

[Ascolong: a new buccal dosage form of acetylsalicylic acid to be used and antiaggregant].

Science.gov (United States)

Kokurina, E V; Suslina, Z A; Khromov, G L; Davydo, A B; Metelitsa, V I; Ionova, V G; Tanashian, M M; Demina, E G; Bochkareva, E V; Belolipetskaia, V G; Deev, A D; Kucheriaeva, N G; Zidra, S I; Gorin, N N; Rumiantsev, D O

1998-01-01

Study of the tolerance and pharmacodynamic and pharmacokinetic characteristics of ascolong, a new buccal dosage form of aspirin containing a very low dose of acetylsalicylic acid (ASA): 12.5 mg. The study was carried out in 43 healthy men (assessment of the drug tolerance) and 19 male patients with coronary disease or cerebrovascular disorders. In 10 patients the antiaggregant efficacy of ascolong administered once or regularly (for 2 weeks) in a dose of 12.5 mg was compared with placebo, in 9 patients a random cross study of 2-week courses of ascolong and Russian aspirin tablets in a dose of 100 mg was carried out. Platelet aggregation was assessed on days 1 and 14 of each course before and 2, 4, and 24 h after the drug intake. Ascolong containing a very low dose of ASA exerts a reliable antiaggregant effect after a single and regular intake, although this effect is less manifest than after aspirin tablets. Profiles of ASA concentrations in the blood were studied. Transbuccal entry of ASA in systemic circulation decelerated its metabolism into a less active metabolite, salicylic acid, due to which fact the ASA microdose had an expressed antiaggregant effect. The drug was sufficiently well tolerated. The new buccal film form of aspirin containing a very low dose of ASA possesses a good antiaggregant effect and is promising in subjects with contraindications to oral intake of aspirin.

European AIDS Clinical Society (EACS) guidelines on the prevention and management of metabolic diseases in HIV

NARCIS (Netherlands)

Lundgren, J. D.; Battegay, M.; Behrens, G.; de Wit, S.; Guaraldi, G.; Katlama, C.; Martinez, E.; Nair, D.; Powderly, W. G.; Reiss, P.; Sutinen, J.; Vigano, A.

2008-01-01

BACKGROUND: Metabolic diseases are frequently observed in HIV-infected persons and, as the risk of contracting these diseases is age-related, their prevalence will increase in the future as a consequence of the benefits of antiretroviral therapy (ART). SUMMARY OF GUIDELINES: All HIV-infected persons

The shaping and functional consequences of the dosage effect landscape in multiple myeloma.

Science.gov (United States)

Samur, Mehmet K; Shah, Parantu K; Wang, Xujun; Minvielle, Stéphane; Magrangeas, Florence; Avet-Loiseau, Hervé; Munshi, Nikhil C; Li, Cheng

2013-10-02

Multiple myeloma (MM) is a malignant proliferation of plasma B cells. Based on recurrent aneuploidy such as copy number alterations (CNAs), myeloma is divided into two subtypes with different CNA patterns and patient survival outcomes. How aneuploidy events arise, and whether they contribute to cancer cell evolution are actively studied. The large amount of transcriptomic changes resultant of CNAs (dosage effect) pose big challenges for identifying functional consequences of CNAs in myeloma in terms of specific driver genes and pathways. In this study, we hypothesize that gene-wise dosage effect varies as a result from complex regulatory networks that translate the impact of CNAs to gene expression, and studying this variation can provide insights into functional effects of CNAs. We propose gene-wise dosage effect score and genome-wide karyotype plot as tools to measure and visualize concordant copy number and expression changes across cancer samples. We find that dosage effect in myeloma is widespread yet variable, and it is correlated with gene expression level and CNA frequencies in different chromosomes. Our analysis suggests that despite the enrichment of differentially expressed genes between hyperdiploid MM and non-hyperdiploid MM in the trisomy chromosomes, the chromosomal proportion of dosage sensitive genes is higher in the non-trisomy chromosomes. Dosage-sensitive genes are enriched by genes with protein translation and localization functions, and dosage resistant genes are enriched by apoptosis genes. These results point to future studies on differential dosage sensitivity and resistance of pro- and anti-proliferation pathways and their variation across patients as therapeutic targets and prognosis markers. Our findings support the hypothesis that recurrent CNAs in myeloma are selected by their functional consequences. The novel dosage effect score defined in this work will facilitate integration of copy number and expression data for identifying driver

Metabolic syndrome, diet and exercise.

Science.gov (United States)

De Sousa, Sunita M C; Norman, Robert J

2016-11-01

Polycystic ovary syndrome (PCOS) is associated with a range of metabolic complications including insulin resistance (IR), obesity, dyslipidaemia, hypertension, obstructive sleep apnoea (OSA) and non-alcoholic fatty liver disease. These compound risks result in a high prevalence of metabolic syndrome and possibly increased cardiovascular (CV) disease. As the cardiometabolic risk of PCOS is shared amongst the different diagnostic systems, all women with PCOS should undergo metabolic surveillance though the precise approach differs between guidelines. Lifestyle interventions consisting of increased physical activity and caloric restriction have been shown to improve both metabolic and reproductive outcomes. Pharmacotherapy and bariatric surgery may be considered in resistant metabolic disease. Issues requiring further research include the natural history of PCOS-associated metabolic disease, absolute CV risk and comparative efficacy of lifestyle interventions. Copyright © 2016 Elsevier Ltd. All rights reserved.

Insulin resistance and protein energy metabolism in patients with advanced chronic kidney disease.

Science.gov (United States)

Siew, Edward D; Ikizler, Talat Alp

2010-01-01

Insulin resistance (IR), the reciprocal of insulin sensitivity is a known complication of advanced chronic kidney disease (CKD) and is associated with a number of metabolic derangements. The complex metabolic abnormalities observed in CKD such as vitamin D deficiency, obesity, metabolic acidosis, inflammation, and accumulation of "uremic toxins" are believed to contribute to the etiology of IR and acquired defects in the insulin-receptor signaling pathway in this patient population. Only a few investigations have explored the validity of commonly used assessment methods in comparison to gold standard hyperinsulinemic hyperglycemic clamp technique in CKD patients. An important consequence of insulin resistance is its role in the pathogenesis of protein energy wasting, a state of metabolic derangement characterized by loss of somatic and visceral protein stores not entirely accounted for by inadequate nutrient intake. In the general population, insulin resistance has been associated with accelerated protein catabolism. Among end-stage renal disease (ESRD) patients, enhanced muscle protein breakdown has been observed in patients with Type II diabetes compared to ESRD patients without diabetes. In the absence of diabetes mellitus (DM) or severe obesity, insulin resistance is detectable in dialysis patients and strongly associated with increased muscle protein breakdown, primarily mediated by the ubiquitin-proteasome pathway. Recent epidemiological data indicate a survival advantage and better nutritional status in insulin-free Type II DM patients treated with insulin sensitizer thiazolidinediones. Given the high prevalence of protein energy wasting in ESRD and its unequivocal association with adverse clinical outcomes, insulin resistance may represent an important modifiable target for intervention in the ESRD population.

Doubled dosage of sofosbuviris expected for inhibiting Zika virus infection

Institute of Scientific and Technical Information of China (English)

Somsri Wiwanitkit; Viroj Wiwanitkit

2017-01-01

Sofosbuvir is a new antiviral drug that has been recommended for management of hepatitis C virus (HCV) for a few years. New researches support that sofosbuvir might be useful for the management of Zika virus infection. Based on the pharmacological activity, inhibiting the HCV RNA-dependent RNA polymerase (RdRp or NS5 protein), sofosbuvir is proposed for its effectiveness against Zika virus infection. Here, the authors used a mathematical modelling theoretical approach to predict the expected dosage of sofosbuvir for inhibiting Zika virus infection. Based on the modeling study, if sofosbuvir is assigned for management of Zika virus infection, doubled dosage of the present dosage for hepatitis C management is recommended.

Dosage of boron traces in graphite, uranium and beryllium oxide

International Nuclear Information System (INIS)

Coursier, J.; Hure, J.; Platzer, R.

1955-01-01

The problem of the dosage of the boron in the materials serving to the construction of nuclear reactors arises of the following way: to determine to about 0,1 ppm close to the quantities of boron of the order of tenth ppm. We have chosen the colorimetric analysis with curcumin as method of dosage. To reach the indicated contents, it is necessary to do a previous separation of the boron and the materials of basis, either by extraction of tetraphenylarsonium fluoborate in the case of the boron dosage in uranium and the beryllium oxide, either by the use of a cations exchanger resin of in the case of graphite. (M.B.) [fr

A fresh look at metabolic bone diseases in reptiles and amphibians.

Science.gov (United States)

Klaphake, Eric

2010-09-01

Metabolic bone diseases (MBDs) are a common presenting complaint in reptiles and amphibians to veterinarians; however, understanding of the causes and diagnostic and treatment options is often extrapolated from human or other mammalian medicine models. Although the roles of UV-B, calcium, phosphorus, and cholecalciferol are better understood in some MBDs, there remain many X factors that are not. Likewise, quantitative diagnosis of MBDs has been difficult not only in terms of staging a disease but also regarding whether or not a condition is present. Treatment options also present challenges in corrective husbandry and diet modifications, medication/modality selection, and dosing/regimen parameters. Copyright 2010 Elsevier Inc. All rights reserved.

Diagnosis and management of non-alcoholic fatty liver disease and related metabolic disorders: Consensus statement from the Study Group of Liver and Metabolism, Chinese Society of Endocrinology

Science.gov (United States)

Gao, Xin; Fan, Jian-Gao

2013-01-01

Non-alcoholic fatty liver disease (NAFLD) is the most common liver disease in Western countries, affecting 20%–33% of the general population. Large population-based surveys in China indicate a prevalence of approximately 15%–30%. Worldwide, including in China, the prevalence of NAFLD has increased rapidly in parallel with regional trends of obesity, type2 diabetes and metabolic syndrome. In addition, NAFLD has contributed significantly to increased overall, as well as cardiovascular and liver-related, mortality in the general population. In view of rapid advances in research into NAFLD in recent years, this consensus statement provides a brief update on the progress in the field and suggests preferred approaches for the comprehensive management of NAFLD and its related metabolic diseases. PMID:23560695

The Cardiomyocyte RNA-Binding Proteome: Links to Intermediary Metabolism and Heart Disease

Directory of Open Access Journals (Sweden)

Yalin Liao

2016-08-01

Full Text Available RNA functions through the dynamic formation of complexes with RNA-binding proteins (RBPs in all clades of life. We determined the RBP repertoire of beating cardiomyocytic HL-1 cells by jointly employing two in vivo proteomic methods, mRNA interactome capture and RBDmap. Together, these yielded 1,148 RBPs, 391 of which are shared with all other available mammalian RBP repertoires, while 393 are thus far unique to cardiomyocytes. RBDmap further identified 568 regions of RNA contact within 368 RBPs. The cardiomyocyte mRNA interactome composition reflects their unique biology. Proteins with roles in cardiovascular physiology or disease, mitochondrial function, and intermediary metabolism are all highly represented. Notably, we identified 73 metabolic enzymes as RBPs. RNA-enzyme contacts frequently involve Rossmann fold domains with examples in evidence of both, mutual exclusivity of, or compatibility between RNA binding and enzymatic function. Our findings raise the prospect of previously hidden RNA-mediated regulatory interactions among cardiomyocyte gene expression, physiology, and metabolism.

Myocardial Infarction and Ischemic Heart Disease in Overweight and Obesity With and Without Metabolic Syndrome

DEFF Research Database (Denmark)

Thomsen, Mette; Nordestgaard, Børge G

2014-01-01

IMPORTANCE: Overweight and obesity likely cause myocardial infarction (MI) and ischemic heart disease (IHD); however, whether coexisting metabolic syndrome is a necessary condition is unknown. OBJECTIVE: To test the hypothesis that overweight and obesity with and without metabolic syndrome...... syndrome. MAIN OUTCOMES AND MEASURES: Hazard ratios for incident MI and IHD according to combinations of BMI category and absence or presence of metabolic syndrome. RESULTS: During a median of 3.6 years' follow-up, we recorded 634 incident MI and 1781 incident IHD events. For MI, multivariable adjusted...... hazard ratios vs normal weight individuals without metabolic syndrome were 1.26 (95% CI, 1.00-1.61) in overweight and 1.88 (95% CI, 1.34-2.63) in obese individuals without metabolic syndrome and 1.39 (95% CI, 0.96-2.02) in normal weight, 1.70 (95% CI, 1.35-2.15) in overweight, and 2.33 (95% CI, 1...

Does canine inflammatory bowel disease influence gut microbial profile and host metabolism?

Science.gov (United States)

Xu, Jia; Verbrugghe, Adronie; Lourenço, Marta; Janssens, Geert P J; Liu, Daisy J X; Van de Wiele, Tom; Eeckhaut, Venessa; Van Immerseel, Filip; Van de Maele, Isabel; Niu, Yufeng; Bosch, Guido; Junius, Greet; Wuyts, Brigitte; Hesta, Myriam

2016-06-16

Inflammatory bowel disease (IBD) refers to a diverse group of chronic gastrointestinal diseases, and gut microbial dysbiosis has been proposed as a modulating factor in its pathogenesis. Several studies have investigated the gut microbial ecology of dogs with IBD but it is yet unclear if this microbial profile can alter the nutrient metabolism of the host. The aim of the present study was to characterize the faecal bacterial profile and functionality as well as to determine host metabolic changes in IBD dogs. Twenty-three dogs diagnosed with IBD and ten healthy control dogs were included. Dogs with IBD were given a clinical score using the canine chronic enteropathy clinical activity index (CCECAI). Faecal short-chain fatty acids (SCFA) and ammonia concentrations were measured and quantitative PCR was performed. The concentration of plasma amino acids, acylcarnitines, serum folate, cobalamin, and indoxyl sulfate was determined. No significant differences in the abundance of a selection of bacterial groups and fermentation metabolites were observed between the IBD and control groups. However, significant negative correlations were found between CCECAI and the faecal proportion of Lactobacillus as well as between CCECAI and total SCFA concentration. Serum folate and plasma citrulline were decreased and plasma valine was increased in IBD compared to control dogs. Increased plasma free carnitine and total acylcarnitines were observed in IBD compared with control dogs, whereas short-chain acylcarnitines (butyrylcarnitine + isobutyrylcarnitine and, methylmalonylcarnitine) to free carnitine ratios decreased. Dogs with IBD had a higher 3-hydroxyisovalerylcarnitine + isovalerylcarnitine to leucine ratio compared to control dogs. Canine IBD induced a wide range of changes in metabolic profile, especially for the plasma concentrations of short-chain acylcarnitines and amino acids, which could have evolved from tissue damage and alteration in host metabolism. In

Sphingolipid metabolism correlates with cerebrospinal fluid Beta amyloid levels in Alzheimer's disease.

Directory of Open Access Journals (Sweden)

Alfred N Fonteh

Full Text Available Sphingolipids are important in many brain functions but their role in Alzheimer's disease (AD is not completely defined. A major limit is availability of fresh brain tissue with defined AD pathology. The discovery that cerebrospinal fluid (CSF contains abundant nanoparticles that include synaptic vesicles and large dense core vesicles offer an accessible sample to study these organelles, while the supernatant fluid allows study of brain interstitial metabolism. Our objective was to characterize sphingolipids in nanoparticles representative of membrane vesicle metabolism, and in supernatant fluid representative of interstitial metabolism from study participants with varying levels of cognitive dysfunction. We recently described the recruitment, diagnosis, and CSF collection from cognitively normal or impaired study participants. Using liquid chromatography tandem mass spectrometry, we report that cognitively normal participants had measureable levels of sphingomyelin, ceramide, and dihydroceramide species, but that their distribution differed between nanoparticles and supernatant fluid, and further differed in those with cognitive impairment. In CSF from AD compared with cognitively normal participants: a total sphingomyelin levels were lower in nanoparticles and supernatant fluid; b levels of ceramide species were lower in nanoparticles and higher in supernatant fluid; c three sphingomyelin species were reduced in the nanoparticle fraction. Moreover, three sphingomyelin species in the nanoparticle fraction were lower in mild cognitive impairment compared with cognitively normal participants. The activity of acid, but not neutral sphingomyelinase was significantly reduced in the CSF from AD participants. The reduction in acid sphingomylinase in CSF from AD participants was independent of depression and psychotropic medications. Acid sphingomyelinase activity positively correlated with amyloid β42 concentration in CSF from cognitively normal but

Metabolic and hormonal signatures in pre-manifest and manifest Huntington’s disease patients

Directory of Open Access Journals (Sweden)

Rui eWang

2014-06-01

Full Text Available Huntington's disease (HD is an inherited neurodegenerative disorder typified by involuntary body movements, and psychiatric and cognitive abnormalities. Many HD patients also exhibit metabolic changes including progressive weight loss and appetite dysfunction. Here we have investigated metabolic function in pre-manifest and manifest HD subjects to establish an HD subject metabolic hormonal plasma signature. Individuals at risk for HD who have had predictive genetic testing showing the cytosine-adenine-guanine (CAG expansion causative of HD, but who do not yet present signs and symptoms sufficient for the diagnosis of manifest HD are said to be pre-manifest. Pre-manifest and manifest HD patients, as well as both familial and non-familial controls, were evaluated for multiple peripheral metabolism signals including circulating levels of hormones, growth factors, lipids and cytokines. Both pre-manifest and manifest HD subjects exhibited significantly reduced levels of circulating growth factors, including growth hormone and prolactin. HD-related changes in the levels of metabolic hormones such as ghrelin, glucagon and amylin were also observed. Total cholesterol, HDL-C and LDL-C were significantly decreased in HD subjects. C-reactive protein was significantly elevated in pre-manifest HD subjects. The observation of metabolic alterations, even in subjects considered to be in the pre-manifest stage of HD, suggests that in addition, and prior, to overt neuronal damage, HD affects metabolic hormone secretion and energy regulation, which may shed light on pathogenesis, and provide opportunities for biomarker development.

TaS2 nanosheet-based room-temperature dosage meter for nitric oxide

Directory of Open Access Journals (Sweden)

Qiyuan He

2014-09-01

Full Text Available A miniature dosage meter for toxic gas is developed based on TaS2 nanosheets, which is capable of indicating the toxic dosage of trace level NO at room temperature. The TaS2 film-based chemiresistor shows an irreversible current response against the exposure of NO. The unique non-recovery characteristic makes the TaS2 film-based device an ideal indicator of total dosage of chronicle exposure.

Glycogen Storage Disease Type Ia in Canines: A Model for Human Metabolic and Genetic Liver Disease

OpenAIRE

Specht, Andrew; Fiske, Laurie; Erger, Kirsten; Cossette, Travis; Verstegen, John; Campbell-Thompson, Martha; Struck, Maggie B.; Lee, Young Mok; Chou, Janice Y.; Byrne, Barry J.; Correia, Catherine E.; Mah, Cathryn S.; Weinstein, David A.; Conlon, Thomas J.

2011-01-01

A canine model of Glycogen storage disease type Ia (GSDIa) is described. Affected dogs are homozygous for a previously described M121I mutation resulting in a deficiency of glucose-6-phosphatase-α. Metabolic, clinicopathologic, pathologic, and clinical manifestations of GSDIa observed in this model are described and compared to those observed in humans. The canine model shows more complete recapitulation of the clinical manifestations seen in humans including “lactic acidosis”, larger size,...

Protein and leucine metabolism in maple syrup urine disease

International Nuclear Information System (INIS)

Thompson, G.N.; Bresson, J.L.; Pacy, P.J.; Bonnefont, J.P.; Walter, J.H.; Leonard, J.V.; Saudubray, J.M.; Halliday, D.

1990-01-01

Constant infusions of [13C]leucine and [2H5]phenylalanine were used to trace leucine and protein kinetics, respectively, in seven children with maple syrup urine disease (MSUD) and eleven controls matched for age and dietary protein intake. Despite significant elevations of plasma leucine (mean 351 mumol/l, range 224-477) in MSUD subjects, mean whole body protein synthesis [3.78 +/- 0.42 (SD) g.kg-1. 24 h-1] and catabolism (4.07 +/- 0.46) were similar to control values (3.69 +/- 0.50 and 4.09 +/- 0.50, respectively). The relationship between phenylalanine and leucine fluxes was also similar in MSUD subjects (mean phenylalanine-leucine flux ratio 0.35 +/- 0.07) and previously reported adult controls (0.33 +/- 0.02). Leucine oxidation was undetectable in four of the MSUD subjects and very low in the other three (less than 4 mumol.kg-1.h-1; controls 13-20). These results show that persistent elevation in leucine concentration has no effect on protein synthesis. The marked disturbance in leucine metabolism in MSUD did not alter the relationship between rates of catabolism of protein to phenylalanine and leucine, which provides further support for the validity of the use of a single amino acid to trace whole body protein metabolism. The minimal leucine oxidation in MSUD differs from findings in other inborn metabolic errors and indicates that in patients with classical MSUD there is no significant route of leucine disposal other than through protein synthesis

Metabolic regulation of inflammation.

Science.gov (United States)

Gaber, Timo; Strehl, Cindy; Buttgereit, Frank

2017-05-01

Immune cells constantly patrol the body via the bloodstream and migrate into multiple tissues where they face variable and sometimes demanding environmental conditions. Nutrient and oxygen availability can vary during homeostasis, and especially during the course of an immune response, creating a demand for immune cells that are highly metabolically dynamic. As an evolutionary response, immune cells have developed different metabolic programmes to supply them with cellular energy and biomolecules, enabling them to cope with changing and challenging metabolic conditions. In the past 5 years, it has become clear that cellular metabolism affects immune cell function and differentiation, and that disease-specific metabolic configurations might provide an explanation for the dysfunctional immune responses seen in rheumatic diseases. This Review outlines the metabolic challenges faced by immune cells in states of homeostasis and inflammation, as well as the variety of metabolic configurations utilized by immune cells during differentiation and activation. Changes in cellular metabolism that contribute towards the dysfunctional immune responses seen in rheumatic diseases are also briefly discussed.

Clinical research of bone scan characteristics for metabolic bone diseases

International Nuclear Information System (INIS)

Zhu Ruisen; Luo Qiong; Lu Haikui; Chen Libo; Luo Quanyong

2009-01-01

Characteristic images of 99m Tc-MDP bone scintigraphy in patients with metabolic bone diseases (MBD) were analyzed and compared, in an attempt to improve the capability of differential diagnosis in this aspect. A total of 142 cases, clinically confirmed as (MBD), were categorized into six groups: hyperparathyroidism (117), renal osteodystrophy (4), Paget's disease (16), hypophosphatemic osteomalacia (2), Albers-Schonberg disease (2), and Brittle bone disease (1). They were diagnosed clinically or pathologically, and scanned with 99m Tc-MDP bone scintegraphy, from which the 142 MBD cases were classified into 4 types. The cases of Type I had increased amount of 99m Tc-MDP uptake in whole body bones, including hyperparathyroidism, Albers-Schonberg disease, brittle bone disease and renal osteodystrophy. The cases of Type II had high uptake of 99m Tc-MDP in local region of bones, including paget's disease, hypophosphatemic osteomalacia and hyperparathyroidism. A Type I case with pathological fracture or secondary osteopathy was classified as Type III. Type IV cases were in early stage of hyperparathyroidism, with normal bone scan image. Analysis of the characteristics of 99m Tc-MDP bone scintigraphic findings (locations, morphology and intensities) in patients with MBD may be helpful in the differential diagnosis of MBD, in association with the patient's history and X-ray data altogether. (authors)

Albumin metabolism in health and disease

International Nuclear Information System (INIS)

Kirsch, R.E.; Saunders, S.J.; Brock, J.F.

1979-01-01

Studies performed at the University of Cape Town on the metabolism of albumin have been reviewed. The control of albumin metabolism in protein energy malnutrition, in acute exposure to alcohol and after partial hepatectomy in the rat is discussed

Albumin metabolism in health and disease

Energy Technology Data Exchange (ETDEWEB)

Kirsch, R E; Saunders, S J; Brock, J F [Cape Town Univ. (South Africa). Dept. of Medicine

1979-11-24

Studies performed at the University of Cape Town on the metabolism of albumin have been reviewed. The control of albumin metabolism in protein energy malnutrition, in acute exposure to alcohol and after partial hepatectomy in the rat is discussed.

Developmental plasticity and epigenetic mechanisms underpinning metabolic and cardiovascular diseases.

Science.gov (United States)

Low, Felicia M; Gluckman, Peter D; Hanson, Mark A

2011-06-01

The importance of developmental factors in influencing the risk of later-life disease has a strong evidence base derived from multiple epidemiological, clinical and experimental studies in animals and humans. During early life, an organism is able to adjust its phenotypic development in response to environmental cues. Such developmentally plastic responses evolved as a fitness-maximizing strategy to cope with variable environments. There are now increasing data that these responses are, at least partially, underpinned by epigenetic mechanisms. A mismatch between the early and later-life environments may lead to inappropriate early life-course epigenomic changes that manifest in later life as increased vulnerability to disease. There is also growing evidence for the transgenerational transmission of epigenetic marks. This article reviews the evidence that susceptibility to metabolic and cardiovascular disease in humans is linked to changes in epigenetic marks induced by early-life environmental cues, and discusses the clinical, public health and therapeutic implications that arise.

Metabolic states following accumulation of intracellular aggregates: implications for neurodegenerative diseases.

Directory of Open Access Journals (Sweden)

Alexei Vazquez

Full Text Available The formation of intracellular aggregates is a common etiology of several neurodegenerative diseases. Mitochondrial defects and oxidative stress has been pointed as the major mechanistic links between the accumulation of intracellular aggregates and cell death. In this work we propose a "metabolic cell death by overcrowding" as an alternative hypothesis. Using a model of neuron metabolism, we predict that as the concentration of protein aggregates increases the neurons transit through three different metabolic phases. The first phase (0-6 mM corresponds with the normal neuron state, where the neuronal activity is sustained by the oxidative phosphorylation of lactate. The second phase (6-8.6 mM is characterized by a mixed utilization of lactate and glucose as energy substrates and a switch from ammonia uptake to ammonia release by neurons. In the third phase (8.6-9.3 mM neurons are predicted to support their energy demands from glycolysis and an alternative pathway for energy generation, involving reactions from serine synthesis, one carbon metabolism and the glycine cleavage system. The model also predicts a decrease in the maximum neuronal capacity for energy generation with increasing the concentration of protein aggregates. Ultimately this maximum capacity becomes zero when the protein aggregates reach a concentration of about 9.3 mM, predicting the cessation of neuronal activity.

Peculiarities of Ischemic Heart Disease Course and Treatment in Patients with Glucose Metabolism Impairment and Diabetes Mellitus

Directory of Open Access Journals (Sweden)

O.M. Radchenko

2015-09-01

Full Text Available Combination of ischemic heart disease and diabetes mellitus is characterized by certain features of clinical picture and insufficient effectiveness of treatment of ischemic heart disease. With the aim of investigation of pathogenic mechanisms and features of the clinical course of ischemic heart disease associated with glucose homeostasis violation we examined 116 patients (51 women, 65 men, median of age 63 years old with normal regulation of glucose metabolism (NRG, n = 24, changes in fasting glucose (n = 23, violated glucose tolerance (n = 21, combined violation (n = 24 and diabetes mellitus (n = 24. We also conducted their prospective observation for 40 months with the following endpoints — hospitalization because of cardiovascular complications, death from them and the emergence of diabetes. It was established that ischemic heart disease associated with prediabetic disorders and diabetes mellitus has the following peculiarities: earlier clinical manifestation in women; more frequent and severe heart failure; lower tolerance to physical load in patients with angina pectoris; atypical manifestation of ischemic pain: longer attacks, atypical localization or absent pain; frequent combination with arrhythmias and conduction disorders; frequent affection of multiple coronary arteries, which leads to myocardial infarction with complicated course; eccentric type of left ventricle remodeling; significant calcification of mitral and aortic valves of heart. The main principles of treatment of ischemic heart disease: weight loss; active correction of glucose metabolism violations using medications (metformin even at the stage of prediabetes, because in chronic stable forms of ischemic heart disease metformin significantly improves glucose metabolism, decreases insulin resistance and does not increase the incidence of cardiovascular complications and decompensations of heart failure; the basic drugs for treatment of ischemic heart disease should be

The prevalence of stunting, overweight and obesity, and metabolic disease risk in rural South African children

Directory of Open Access Journals (Sweden)

Dunger David B

2010-03-01

Full Text Available Abstract Background Low- to middle-income countries are undergoing a health transition with non-communicable diseases contributing substantially to disease burden, despite persistence of undernutrition and infectious diseases. This study aimed to investigate the prevalence and patterns of stunting and overweight/obesity, and hence risk for metabolic disease, in a group of children and adolescents in rural South Africa. Methods A cross-sectional growth survey was conducted involving 3511 children and adolescents 1-20 years, selected through stratified random sampling from a previously enumerated population living in Agincourt sub-district, Mpumalanga Province, South Africa. Anthropometric measurements including height, weight and waist circumference were taken using standard procedures. Tanner pubertal assessment was conducted among adolescents 9-20 years. Growth z-scores were generated using 2006 WHO standards for children up to five years and 1977 NCHS/WHO reference for older children. Overweight and obesity for those 2 for overweight and obesity respectively were used for those ≥ 18 years. Waist circumference cut-offs of ≥ 94 cm for males and ≥ 80 cm for females and waist-to-height ratio of 0.5 for both sexes were used to determine metabolic disease risk in adolescents. Results About one in five children aged 1-4 years was stunted; one in three of those aged one year. Concurrently, the prevalence of combined overweight and obesity, almost non-existent in boys, was substantial among adolescent girls, increasing with age and reaching approximately 20-25% in late adolescence. Central obesity was prevalent among adolescent girls, increasing with sexual maturation and reaching a peak of 35% at Tanner Stage 5, indicating increased risk for metabolic disease. Conclusions The study highlights that in transitional societies, early stunting and adolescent obesity may co-exist in the same socio-geographic population. It is likely that this profile

[Cholesterol metabolism and lipid peroxidation processes in hypodynamia. Effect of using ascorbic acid and alpha-tocopherol].

Science.gov (United States)

Elikov, A V; Tsapok, P I

2010-01-01

Study status of cholesterol metabolism, processes of lipid peroxidation and antioxidant protection in blood plasma, erythrocytes and homogenates of the, heart, liver, muscle femors of rats attached to movement active. Establishment effects application of ascorbic acid and alpha-tocopherol. Ascorbic acid and alpha-tocopherol were infused daily. The daily dosage was 2 and 1 mg respectively. Characteristic shift changes of cholesterol metabolism in conditions of limited muscular activity were revealed. It was shown that vitamin antioxidants play a role in correction of metabolic disorders in case of immobile distress syndrome.

Potential Linkage Between Cerebrovascular Diseases and Metabolic Syndrome.

Science.gov (United States)

Jabir, Nasimudeen R; Firoz, Chelapram Kandy; Khan, Mohd Shahnawaz; Zaidi, Syed Kashif; Ashraf, Ghulam Md; Shakil, Shazi; Kamal, Mohammad Amjad; Tabrez, Shams

2017-01-01

Cerebrovascular disease (CD) and metabolic syndrome (MetS) are two devastating health dilemma that continues to be a potential contributor to disability and mortality in human population all across the world. Scientific data clearly shows several mechanistic similarities between these two co-existing and interlinked conditions. The linkage exacerbates ongoing patho-physiological condition towards more lethal events. In view of the presence of modifiable risk factors in both CD and MetS, their management holds potential therapeutic value. Hence, developing common treatment strategies for these diseases could involve common molecular agents. In this communication, we have summarized some of the common pathological conditions viz. abdominal obesity, insulin resistance, dyslipidemia, hypertension, and endothelial dysfunction that further deteriorate existing homeostasis in CD and MetS. Based on our article, it is advocated that substantial improvements in novel multi-targeted drug discovery could provide the effective treatment methods in order to avoid the fatal complications related with CD and MetS. Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.org.

A brief history of dosage compensation

Indian Academy of Sciences (India)

depression of X-linked gene activity in the female, as well as by hyperexpression of the ... to the Harvey lecture, Muller had presented important ideas relative to dosage ... at Columbia. I do recall a talk by the popular physical anthro- pologist ...

Effectiveness of acetazolamide for reversal of metabolic alkalosis in weaning COPD patients from mechanical ventilation.

Science.gov (United States)

Faisy, Christophe; Mokline, Amel; Sanchez, Olivier; Tadié, Jean-Marc; Fagon, Jean-Yves

2010-05-01

To evaluate the effects of a single daily dose of acetazolamide (ACET) on metabolic alkalosis and respiratory parameters in weaning chronic obstructive pulmonary disease (COPD) patients from invasive mechanical ventilation. Case-control study. An 18-bed intensive care unit (ICU) in a university hospital. Twenty-six intubated COPD patients with mixed metabolic alkalosis (serum bicarbonate >26 mmol/l and arterial pH >or=7.38) were compared with a historical control group (n = 26) matched for serum bicarbonate, arterial pH, age, and severity of illness at admission to ICU. ACET administration (500 mg intravenously) was monitored daily according to arterial blood gas analysis from readiness to wean until extubation. ACET was administered 4 (1-11) days throughout the weaning period. Patients with ACET treatment significantly decreased their serum bicarbonate (p = 0.01 versus baseline) and arterial blood pH (p respiratory parameters except PaO(2)/FiO(2) ratio (p = 0.03). ACET patients and their matched controls had similar duration of weaning. Extubation success rate was not significantly different between groups, and causes of reintubation were comparable. ACET used at the dosage of 500 mg per day reduces metabolic alkalosis but has no benefit in terms of improving PaCO(2) or respiratory parameters in weaning COPD patients from mechanical ventilation.

Pathophysiology and molecular basis of selected metabolic abnormalities in Huntington's disease.

Science.gov (United States)

Krzysztoń-Russjan, Jolanta

2016-12-30

Huntington's disease (HD) is an incurable, devastating neurodegenerative disease with a known genetic background and autosomally dominant inheritance pattern. HTT gene mutation (mHTT) is associated with polymorphic fragment elongation above 35 repeats of the CAG triplet. The mHTT product is an altered protein with a poly-Q elongated fragment, with the highest expression determined in the central nervous system (CNS) and with differentiated expression outside the CNS. A drastic loss of striatal and deeper layers of the cerebral cortex neurons was determined in the CNS, but muscle and body weight mass loss with dysfunction of many organs was also observed. HD symptoms include neurological disturbances, such as choreal movements with dystonia, speech and swallowing impairments, and additionally a variety of psychiatric and behavioral symptoms with cognitive decline have been described. They are the result of disturbances of several cellular pathways related to signal transmission, mitochondrial dysfunction and energy metabolism impairment shown by gene and protein expression and alteration of their functions. Impairment of energy processes demonstrated by a decrease of ATP production and increase of oxidative stress markers was determined in- and outside of the CNS in glycolysis, the Krebs cycle and the electron transport chain. A correlation between the increase of energy metabolism impairment level and the increase in number of CAG repeats in HTT has often been described. The energy metabolism study is an initial stage of sensitive biomarkers and a new therapeutic investigative option for early application in order to inhibit pathological processes in HD. Identification of pathological changes outside the CNS requires a reevaluation of diagnostic and therapeutic rules in HD.

Peroxisomes, lipid metabolism, and human disease

NARCIS (Netherlands)

Wanders, R. J.

2000-01-01

In the past few years, much has been learned about the metabolic functions of peroxisomes. These studies have shown that peroxisomes play a major role in lipid metabolism, including fatty acid beta-oxidation, etherphospholipid biosynthesis, and phytanic acid alpha-oxidation. This article describes

Pavor nocturnus: a complication of single daily tricyclic or neuroleptic dosage.

Science.gov (United States)

Flemenbaum, A

1976-05-01

The author tested the hypothesis that a single bedtime dosage schedule of tricyclic or neuroleptic medication produces increased frequency of night terrors by administering a questionnaire to 30 medical patients who were not receiving such medications and 100 psychiatric patients on either multiple- or single-dosage schedules. Psychiatric patients on multiple-dosage schedules reported no more frightening dreams than the medical patients, whereas almost three-fourths of those receiving single bedtime doses had frightening dreams, a significant difference from the medical sample. This preliminary report is presented to call attention to the possible undesirable effects of a single dose schedule.

Genetic Manipulations of PPARs: Effects on Obesity and Metabolic Disease

Directory of Open Access Journals (Sweden)

Yaacov Barak

2007-01-01

Full Text Available The interest in genetic manipulations of PPARs is as old as their discovery as receptors of ligands with beneficial clinical activities. Considering the effects of PPAR ligands on critical aspects of systemic physiology, including obesity, lipid metabolism, insulin resistance, and diabetes, gene knockout (KO in mice is the ideal platform for both hypothesis testing and discovery of new PPAR functions in vivo. With the fervent pursuit of the magic bullet to eradicate the obesity epidemic, special emphasis has been placed on the impacts of PPARs on obesity and its associated diseases. As detailed in this review, understanding how PPARs regulate gene expression and basic metabolic pathways is a necessary intermediate en route to deciphering their effects on obesity. Over a decade and dozens of genetic modifications of PPARs into this effort, valuable lessons have been learned, but we are left with more questions to be answered. These lessons and future prospects are the subject of this review.

21 CFR 522.1662 - Oxytetracycline hydrochloride implantation or injectable dosage forms.

Science.gov (United States)

2010-04-01

... 21 Food and Drugs 6 2010-04-01 2010-04-01 false Oxytetracycline hydrochloride implantation or injectable dosage forms. 522.1662 Section 522.1662 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF... INJECTABLE DOSAGE FORM NEW ANIMAL DRUGS § 522.1662 Oxytetracycline hydrochloride implantation or injectable...

The insulin-like growth factor I system: physiological and pathophysiological implication in cardiovascular diseases associated with metabolic syndrome.

Science.gov (United States)

Ren, Jun; Anversa, Piero

2015-02-15

Metabolic syndrome is a cluster of risk factors including obesity, dyslipidemia, hypertension, and insulin resistance. A number of theories have been speculated for the pathogenesis of metabolic syndrome including impaired glucose and lipid metabolism, lipotoxicity, oxidative stress, interrupted neurohormonal regulation and compromised intracellular Ca(2+) handling. Recent evidence has revealed that adults with severe growth hormone (GH) and insulin-like growth factor I (IGF-1) deficiency such as Laron syndrome display increased risk of stroke and cardiovascular diseases. IGF-1 signaling may regulate contractility, metabolism, hypertrophy, apoptosis, autophagy, stem cell regeneration and senescence in the heart to maintain cardiac homeostasis. An inverse relationship between plasma IGF-1 levels and prevalence of metabolic syndrome as well as associated cardiovascular complications has been identified, suggesting the clinical promises of IGF-1 analogues or IGF-1 receptor activation in the management of metabolic and cardiovascular diseases. However, the underlying pathophysiological mechanisms between IGF-1 and metabolic syndrome are still poorly understood. This mini-review will discuss the role of IGF-1 signaling cascade in the prevalence of metabolic syndrome in particular the susceptibility to overnutrition and sedentary life style-induced obesity, dyslipidemia, insulin resistance and other features of metabolic syndrome. Special attention will be dedicated in IGF-1-associated changes in cardiac responses in various metabolic syndrome components such as insulin resistance, obesity, hypertension and dyslipidemia. The potential risk of IGF-1 and IGF-1R stimulation such as tumorigenesis is discussed. Therapeutic promises of IGF-1 and IGF-1 analogues including mecasermin, mecasermin rinfabate and PEGylated IGF-1 will be discussed. Copyright © 2014 Elsevier Inc. All rights reserved.

GGDonto ontology as a knowledge-base for genetic diseases and disorders of glycan metabolism and their causative genes.

Science.gov (United States)

Solovieva, Elena; Shikanai, Toshihide; Fujita, Noriaki; Narimatsu, Hisashi

2018-04-18

Inherited mutations in glyco-related genes can affect the biosynthesis and degradation of glycans and result in severe genetic diseases and disorders. The Glyco-Disease Genes Database (GDGDB), which provides information about these diseases and disorders as well as their causative genes, has been developed by the Research Center for Medical Glycoscience (RCMG) and released in April 2010. GDGDB currently provides information on about 80 genetic diseases and disorders caused by single-gene mutations in glyco-related genes. Many biomedical resources provide information about genetic disorders and genes involved in their pathogenesis, but resources focused on genetic disorders known to be related to glycan metabolism are lacking. With the aim of providing more comprehensive knowledge on genetic diseases and disorders of glycan biosynthesis and degradation, we enriched the content of the GDGDB database and improved the methods for data representation. We developed the Genetic Glyco-Diseases Ontology (GGDonto) and a RDF/SPARQL-based user interface using Semantic Web technologies. In particular, we represented the GGDonto content using Semantic Web languages, such as RDF, RDFS, SKOS, and OWL, and created an interactive user interface based on SPARQL queries. This user interface provides features to browse the hierarchy of the ontology, view detailed information on diseases and related genes, and find relevant background information. Moreover, it provides the ability to filter and search information by faceted and keyword searches. Focused on the molecular etiology, pathogenesis, and clinical manifestations of genetic diseases and disorders of glycan metabolism and developed as a knowledge-base for this scientific field, GGDonto provides comprehensive information on various topics, including links to aid the integration with other scientific resources. The availability and accessibility of this knowledge will help users better understand how genetic defects impact the

Tandem mass spectrometry: a convenient approach in the dosage of steviol glycosides in Stevia sweetened commercial food beverages.

Science.gov (United States)

Di Donna, L; Mazzotti, F; Santoro, I; Sindona, G

2017-05-01

The use of sweeteners extracted from leaves of the plant species Stevia rebaudiana is increasing worldwide. They are recognized as generally recognized as safe by the US-FDA and approved by EU-European Food Safety Authority, with some recommendation on the daily dosage that should not interfere with glucose metabolism. The results presented here introduce an easy analytical approach for the identification and assay of Stevia sweeteners in commercially available soft drink, based on liquid chromatography coupled to tandem mass spectrometry, using a natural statin-like molecule, Brutieridin, as internal standard. Copyright © 2017 John Wiley & Sons, Ltd. Copyright © 2017 John Wiley & Sons, Ltd.

Pharmacodynamics of combined estrogen-progestin oral contraceptives: 1. Effects on metabolism.

Science.gov (United States)

Bastianelli, Carlo; Farris, Manuela; Rosato, Elena; Brosens, Ivo; Benagiano, Giuseppe

2017-03-01

The risk-benefit profile of any pharmacologic agent must be evaluated against risks connected with the events to be avoided. This is especially true in the case of hormonal contraception, not intended to combat a disease. Over the six decades during which their use has progressively expanded, the risk-benefit profile of combined oral contraceptives (COC) has substantially changed, with new combinations, dosages and mode of administration appearing on the market. Area covered: In a series of articles, recent information on the complex issue of COC risks and benefits will be reviewed in the hope of providing an updated picture. The present article reviews metabolic changes occurring during use of modern combinations of estrogens (ethinyl estradiol, estradiol, estradiol valerate and estetrol) and new progestins (desogestrel, gestodene, dienogest, drospirenone, nomegestrol acetate), often compared to classic compounds, such as levonorgestrel. Three categories of metabolic effects in healthy women are detailed: on carbohydrates, lipid and bone mineral content. Expert commentary: Overall, the picture is reassuring: the new generations of progestins are basically devoid of androgenic, estrogenic or glucocorticoid related side-effects. This should result in an improved safety profile, although past history teaches us that that large comparative and surveillance studies are required before firm conclusions can be drawn. At any rate, available evidence indicates that metabolic effects of third and fourth generation progestins, especially when they are combined with natural estrogens, are minimal and, if used in healthy women, should not cause concern.

Differential retention of metabolic genes following whole-genome duplication.

Science.gov (United States)

Gout, Jean-François; Duret, Laurent; Kahn, Daniel

2009-05-01

Classical studies in Metabolic Control Theory have shown that metabolic fluxes usually exhibit little sensitivity to changes in individual enzyme activity, yet remain sensitive to global changes of all enzymes in a pathway. Therefore, little selective pressure is expected on the dosage or expression of individual metabolic genes, yet entire pathways should still be constrained. However, a direct estimate of this selective pressure had not been evaluated. Whole-genome duplications (WGDs) offer a good opportunity to address this question by analyzing the fates of metabolic genes during the massive gene losses that follow. Here, we take advantage of the successive rounds of WGD that occurred in the Paramecium lineage. We show that metabolic genes exhibit different gene retention patterns than nonmetabolic genes. Contrary to what was expected for individual genes, metabolic genes appeared more retained than other genes after the recent WGD, which was best explained by selection for gene expression operating on entire pathways. Metabolic genes also tend to be less retained when present at high copy number before WGD, contrary to other genes that show a positive correlation between gene retention and preduplication copy number. This is rationalized on the basis of the classical concave relationship relating metabolic fluxes with enzyme expression.

Lack of differential pattern in central adiposity and metabolic syndrome in Barrett's esophagus and gastroesophageal reflux disease.

LENUS (Irish Health Repository)

Healy, L A

2012-02-01

Obesity is an established risk factor for esophageal adenocarcinoma, although the mechanism is unclear. A pathway from reflux to inflammation through metaplasia is the dominant hypothesis, and an added role relating to visceral adiposity and the metabolic syndrome has been mooted in Barrett\\'s esophagus (BE) patients. Whether BE differs from gastroesophageal reflux disease (GERD) in obesity and metabolic syndrome profiles is unclear, and this was the focus of this study. Patients with proven BE or GERD were randomly selected from the unit data registry and invited to attend for metabolic syndrome screening, anthropometry studies including segmental body composition analysis, and laboratory tests including fasting lipids, insulin, and C-reactive protein. Metabolic syndrome was defined using the National Cholesterol Education Program (NCEP) and the International Diabetes Federation (IDF) criteria. One hundred and eighteen BE patients and 113 age- and sex-matched GERD controls were studied. The incidence of obesity (body mass index >30 kg\\/m(2)) was 36% and 38%, respectively, with the pattern of fat deposition predominantly central and an estimated trunk fat mass of 13 and 14 kg, respectively. Using the NCEP criteria, metabolic syndrome was significantly more common in the BE cohort (30% vs 20%, P < 0.05), but there was no significant difference using IDF criteria (42% vs 37%, P= 0.340). Central obesity and the metabolic syndrome are common in both Barrett\\'s and GERD cohorts, but not significantly different, suggesting that central obesity and the metabolic syndrome does not per se impact on the development of BE in a reflux population. In BE, the importance of obesity and the metabolic syndrome in disease progression merits further study.

On the exfoliating polymeric cellular dosage forms for immediate drug release.

Science.gov (United States)

Blaesi, Aron H; Saka, Nannaji

2016-06-01

The most prevalent pharmaceutical dosage forms at present-the oral immediate-release tablets and capsules-are granular solids. Though effective in releasing drug rapidly, development and manufacture of such dosage forms are fraught with difficulties inherent to particulate processing. Predictable dosage form manufacture could be achieved by liquid-based processing, but cast solid dosage forms are not suitable for immediate drug release due to their resistance to fluid percolation. To overcome this limitation, we have recently introduced cellular dosage forms that can be readily prepared from polymeric melts. It has been shown that open-cell structures comprising polyethylene glycol 8000 (PEG 8k) excipient and a drug exfoliate upon immersion in a dissolution medium. The drug is then released rapidly due to the large specific surface area of the exfoliations. In this work, we vary the molecular weight of the PEG excipient and investigate its effect on the drug release kinetics of structures with predominantly open-cell topology. We demonstrate that the exfoliation rate decreases substantially if the excipient molecular weight is increased from 12 to 100kg/mol, which causes the drug dissolution time to increase by more than a factor of ten. A model is then developed to elucidate the exfoliation behavior of cellular structures. Diverse transport processes are considered: percolation due to capillarity, diffusion of dissolution medium through the cell walls, and viscous flow of the saturated excipient. It is found that the lower exfoliation rate and the longer dissolution time of the dosage forms with higher excipient molecular weight are primarily due to the greater viscosity of the cell walls after fluid penetration. Copyright © 2016 Elsevier B.V. All rights reserved.

Skeletal muscle metabolism during prolonged exercise in Pompe disease

DEFF Research Database (Denmark)

Preisler, Nicolai; Laforêt, Pascal; Madsen, Karen Lindhardt

2017-01-01

of exercise, it is important in Pompe disease to acquire more information about muscle substrate use during exercise. METHODS: Seven adults with Pompe disease were matched to a healthy control group (1:1). We determined (1) peak oxidative capacity (VO2peak) and (2) carbohydrate and fatty acid metabolism...... during submaximal exercise (33 W) for 1 h, using cycle-ergometer exercise, indirect calorimetry and stable isotopes. RESULTS: In the patients, VO2peak was less than half of average control values; mean difference -1659 mL/min (CI: -2450 to -867, P = 0.001). However, the respiratory exchange ratio...... increased to >1.0 and lactate levels rose 5-fold in the patients, indicating significant glycolytic flux. In line with this, during submaximal exercise, the rates of oxidation (ROX) of carbohydrates and palmitate were similar between patients and controls (mean difference 0.226 g/min (CI: 0.611 to -0.078, P...

Metabolic pattern analysis of early detection in Alzheimer's disease from other types of dementias and correlated with cognitive function

International Nuclear Information System (INIS)

Ju, R. H.; Lee, C. W.; Jung, Y. A.; Sohn, H. S.; Kim, S. H.; Seo, T. S

2004-01-01

PET/CT studies have demonstrated temporoparietal hypometabolism in probable and definite Alzheimer's disease (AD), a pattern that may help differentiate AD from other types of dementias. Seeking to distinguish Dementia with Lewy bodies (DLB) and Alzheimer's disease (AD), we examined brain glucose metabolism of DLB and AD. Identification of individual differences in patterns of regional cerebral glucose metabolism (rCMRglc) interactions may be important for early detection of AD. We elucidate the relationship between reduced cognitive function and cerebral metabolism. Ten patients with the diagnosis of AD, 3 DLB patients underwent 18F-FDG PET CT. We applied statistical mapping procedure to evaluate the diagnostic power of rCMRglc patterns for differentiation and also correlated with Korean-mini mental status exam (K-MMSE) score include orientation time, place, registration, attention, calculation, recaIl, language and visuospatial function. Glucose metabolic pattern analysis confirmed AD and DLB patients showed significant metabolic reductions involving parietotemporal association, posterior cingulate, and frontal association cortex. DLB patients showed significant metabolic reductions in the occipital cortex, particularly in the primary visual cortex. Covariate analysis revealed that occipital metabolic changes in DLB were independent from those in the adjacent parietotemporal cortices. AnaIysis of clinically diagnosed probable AD patients showed a significantly higher frequency of primary visual metabolic reduction among patients who fulfilled clinical criteria for DLB. occipital hypometabolism is a potential discriminate marker to distinguish DLB versus AD

Prevalence of Metabolic Syndrome in Children With Type 1 Diabetes in South of Iran

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Saki

2016-08-01

Full Text Available Objectives The aim of this study was to investigate the prevalence of metabolic syndrome, in children with type one diabetes mellitus (T1DM for the first time in a population in the Middle East, and assess the influence of type of insulin therapy, daily dosage of insulin, family history of type 2 diabetes, gender and level of HbA1c on the prevalence of metabolic syndrome. Methods This cross-sectional study was conducted on children with T1DM aged 2 years during years 2013 to 2014. Waist circumference, blood pressure, height and weight of children with diabetes, for calculation of body mass index (BMI, were measured by one physician. Fasting blood glucose and lipids were also measured. According to the age-modified standards of the ATPIII, metabolic syndrome was defined. All data were analyzed using the SPSS 18 software. Results In this study, 87 children with diabetes (48 females and 39 males aged 12.38 ± 4.2 were enrolled. Overall, 40.9% of our patients had hypertension, 55.2% had hypertriglyceridemia, 36.8% had low high-density lipoprotein (HDL and 6.9% of patients had abdominal obesity. Furthermore, 29.9% of these children had metabolic syndrome, which did not have a significant association with the type of insulin regimen (P = 0.97, nor the daily dosage of insulin (P = 0.234, however the serum concentration of HbA1c had a significant correlation with metabolic syndrome (P = 0.027. Conclusions This study provides evidence indicating high prevalence of metabolic syndrome in children with T1DM in southern Iran. Preventive programs aimed towards decreasing the risk factors of metabolic syndrome and interpretation of a healthier diet and physical activity for children with T1DM should be considered in our country.

Effect of oxandrolone on glucose metabolism in growth hormone-treated girls with Turner syndrome

NARCIS (Netherlands)

Menke, L.A.; Sas, T.C.J.; Stijnen, T.; Zandwijken, G.R.; Muinck Keizer-Schrama, S.M.P.F. de; Otten, B.J.; Wit, J.M.

2011-01-01

BACKGROUND: The weak androgen oxandrolone (Ox) may increase height but may also affect glucose metabolism in girls with Turner syndrome (TS). METHODS: In a randomized, placebo-controlled, double-blind study, we assessed the effect of Ox at a dosage of either 0.06 or 0.03 mg/kg/day on glucose

[Changes in mineral metabolism in stage 3, 4, and 5 chronic kidney disease (not on dialysis)].

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Lorenzo Sellares, V; Torregrosa, V

2008-01-01

With progression of chronic kidney disease (CKD), disorders of mineral metabolism appear. The classic sequence of events begins with a deficit of calcitriol synthesis and retention of phosphorus. As a result of this, serum calcium decreases and parathyroid hormone (PTH) is stimulated, producing in the bone the high turnover (HT) bone disease known as osteitis fibrosa while on the other extreme we find the forms of low turnover (LT) bone disease. Described later and initially associated with aluminum intoxication, these diseases are now seen primarily in older and/or diabetic patients, who in a uremic setting have relatively low levels of PTH to maintain normal bone turnover. Osteomalacia is also included in this group, which after the disappearance of aluminum intoxication is rarely observed. LT forms of hyperparathyroidism facilitate the exit of calcium (Ca) and phosphorus (P) from bone, whereas the adynamic bone limits the incorporation of Ca and P into bone tissue. Therefore, both forms facilitate the availability of Ca and P, which ends up being deposited in soft tissues such as arteries. The link between bone disease and vascular calcifications in CKD is now a well-established phenomenon. 2. Diagnostic strategies Calcium, Phosphorus They have little capacity to predict underlying bone disease, but their regular measurement is decisive for therapeutic management of the patient, especially in the dose titration stages of intestinal phosphorus binders, vitamin D analogs or calcimimetics. Ideally, Ca++ should be used, but total Ca is routinely used. It is recommended to adjust albumin levels in the event of hypoalbuminemia (for each g/dL of decrease in albumin, total serum Ca decreases 0.9 mg/dL). The following formula facilitates rapid calculation of corrected total calcium: Corrected total Ca (mg/dL) = total Ca (mg/dL) + 0.8 [4-albumina (g/dL)]. Parathyroid hormone "Intact" PTH is the biochemical parameter that best correlates with bone histology (levels

Serotonergic dysfunctions and abnormal iron metabolism: Relevant to mental fatigue of Parkinson disease.

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Zuo, Li-Jun; Yu, Shu-Yang; Hu, Yang; Wang, Fang; Piao, Ying-Shan; Lian, Teng-Hong; Yu, Qiu-Jin; Wang, Rui-Dan; Li, Li-Xia; Guo, Peng; Du, Yang; Zhu, Rong-Yan; Jin, Zhao; Wang, Ya-Jie; Wang, Xiao-Min; Chan, Piu; Chen, Sheng-Di; Wang, Yong-Jun; Zhang, Wei

2016-12-21

Fatigue is a very common non-motor symptom in Parkinson disease (PD) patients. It included physical fatigue and mental fatigue. The potential mechanisms of mental fatigue involving serotonergic dysfunction and abnormal iron metabolism are still unknown. Therefore, we evaluated the fatigue symptoms, classified PD patients into fatigue group and non-fatigue group, and detected the levels of serotonin, iron and related proteins in CSF and serum. In CSF, 5-HT level is significantly decreased and the levels of iron and transferrin are dramatically increased in fatigue group. In fatigue group, mental fatigue score is negatively correlated with 5-HT level in CSF, and positively correlated with the scores of depression and excessive daytime sleepiness, and disease duration, also, mental fatigue is positively correlated with the levels of iron and transferrin in CSF. Transferrin level is negatively correlated with 5-HT level in CSF. In serum, the levels of 5-HT and transferrin are markedly decreased in fatigue group; mental fatigue score exhibits a negative correlation with 5-HT level. Thus serotonin dysfunction in both central and peripheral systems may be correlated with mental fatigue through abnormal iron metabolism. Depression, excessive daytime sleepiness and disease duration were the risk factors for mental fatigue of PD.

Chronic obstructive pulmonary disease may be one of the terminal end points of metabolic syndrome

International Nuclear Information System (INIS)

Helvaci, M.R.; Aydin, L.Y.; Aydin, Y.

2012-01-01

Objective: We tried to understand presence of any effect of excess weight on respiratory system by means of excessive adipose tissue functioning as an endocrine organ and causing a Methodology: Mild (stage 1), moderate (stage 2), and severe (stage 3 and 4) chronic obstructive pulmonary disease (COPD) patients were detected, and compared according to the metabolic parameters in between. Results: There were 145, 56, and 34 patients in the mild, moderate, and severe COPD groups, respectively. The mean age increased gradually (52.4, 56.4, and 60.0 years) from the mild towards the severe COPD groups, respectively (p<0.05 nearly in all steps). Similarly, the mean direction (p<0.05 nearly in all steps). Parallel to them, the mean body mass index increased Conclusion: The metabolic syndrome includes some reversible indicators such as overweight, hyperbetalipoproteinemia, hypertriglyceridemia, dyslipidemia, impaired fasting glucose, impaired glucose tolerance, and white coat hypertension for the development of terminal diseases including obesity, hypertension, diabetes mellitus, peripheral artery disease, coronary heart disease, and stroke. In our opinion, COPD may be one of the terminal end points of the syndrome. (author)

Chronic obstructive pulmonary disease may be one of the terminal end points of metabolic syndrome

Energy Technology Data Exchange (ETDEWEB)

Helvaci, M R; Aydin, L Y; Aydin, Y

2012-04-15

Objective: We tried to understand presence of any effect of excess weight on respiratory system by means of excessive adipose tissue functioning as an endocrine organ and causing a Methodology: Mild (stage 1), moderate (stage 2), and severe (stage 3 and 4) chronic obstructive pulmonary disease (COPD) patients were detected, and compared according to the metabolic parameters in between. Results: There were 145, 56, and 34 patients in the mild, moderate, and severe COPD groups, respectively. The mean age increased gradually (52.4, 56.4, and 60.0 years) from the mild towards the severe COPD groups, respectively (p<0.05 nearly in all steps). Similarly, the mean direction (p<0.05 nearly in all steps). Parallel to them, the mean body mass index increased Conclusion: The metabolic syndrome includes some reversible indicators such as overweight, hyperbetalipoproteinemia, hypertriglyceridemia, dyslipidemia, impaired fasting glucose, impaired glucose tolerance, and white coat hypertension for the development of terminal diseases including obesity, hypertension, diabetes mellitus, peripheral artery disease, coronary heart disease, and stroke. In our opinion, COPD may be one of the terminal end points of the syndrome. (author)

The shift work and health research agenda: Considering changes in gut microbiota as a pathway linking shift work, sleep loss and circadian misalignment, and metabolic disease.

Science.gov (United States)

Reynolds, Amy C; Paterson, Jessica L; Ferguson, Sally A; Stanley, Dragana; Wright, Kenneth P; Dawson, Drew

2017-08-01

Prevalence and impact of metabolic disease is rising. In particular, overweight and obesity are at epidemic levels and are a leading health concern in the Western world. Shift work increases the risk of overweight and obesity, along with a number of additional metabolic diseases, including metabolic syndrome and type 2 diabetes (T2D). How shift work contributes to metabolic disease has not been fully elucidated. Short sleep duration is associated with metabolic disease and shift workers typically have shorter sleep durations. Short sleep durations have been shown to elicit a physiological stress response, and both physiological and psychological stress disrupt the healthy functioning of the intestinal gut microbiota. Recent findings have shown altered intestinal microbial communities and dysbiosis of the gut microbiota in circadian disrupted mice and jet lagged humans. We hypothesize that sleep and circadian disruption in humans alters the gut microbiota, contributing to an inflammatory state and metabolic disease associated with shift work. A research agenda for exploring the relationship between insufficient sleep, circadian misalignment and the gut microbiota is provided. Copyright © 2016 Elsevier Ltd. All rights reserved.

Reciprocal Effects on Neurocognitive and Metabolic Phenotypes in Mouse Models of 16p11.2 Deletion and Duplication Syndromes.

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Thomas Arbogast

2016-02-01

Full Text Available The 16p11.2 600 kb BP4-BP5 deletion and duplication syndromes have been associated with developmental delay; autism spectrum disorders; and reciprocal effects on the body mass index, head circumference and brain volumes. Here, we explored these relationships using novel engineered mouse models carrying a deletion (Del/+ or a duplication (Dup/+ of the Sult1a1-Spn region homologous to the human 16p11.2 BP4-BP5 locus. On a C57BL/6N inbred genetic background, Del/+ mice exhibited reduced weight and impaired adipogenesis, hyperactivity, repetitive behaviors, and recognition memory deficits. In contrast, Dup/+ mice showed largely opposite phenotypes. On a F1 C57BL/6N × C3B hybrid genetic background, we also observed alterations in social interaction in the Del/+ and the Dup/+ animals, with other robust phenotypes affecting recognition memory and weight. To explore the dosage effect of the 16p11.2 genes on metabolism, Del/+ and Dup/+ models were challenged with high fat and high sugar diet, which revealed opposite energy imbalance. Transcriptomic analysis revealed that the majority of the genes located in the Sult1a1-Spn region were sensitive to dosage with a major effect on several pathways associated with neurocognitive and metabolic phenotypes. Whereas the behavioral consequence of the 16p11 region genetic dosage was similar in mice and humans with activity and memory alterations, the metabolic defects were opposite: adult Del/+ mice are lean in comparison to the human obese phenotype and the Dup/+ mice are overweight in comparison to the human underweight phenotype. Together, these data indicate that the dosage imbalance at the 16p11.2 locus perturbs the expression of modifiers outside the CNV that can modulate the penetrance, expressivity and direction of effects in both humans and mice.

Metabolic Syndrome

Science.gov (United States)

Metabolic syndrome is a group of conditions that put you at risk for heart disease and diabetes. These conditions ... agree on the definition or cause of metabolic syndrome. The cause might be insulin resistance. Insulin is ...

The influence of black cumin seed oil therapy with dosage of 1.5 mL/day and 3 mL/day to interleukin-21 (IL-21) expression of the patients with metabolic syndrome risk

Science.gov (United States)

Fajar, D. R.; Akrom; Darmawan, E.

2017-11-01

Metabolic syndrome (MS) is a metabolic disorder caused by obesity and insulin resistance. In the state of obesity and insulin resistance occurs increased fat metabolism that causes production reactive oxygen species (ROS) and oxidative stress that makes dysregulation of adipose tissue that decreases antioxidant enzymes and immune system disorders. In diabetes mellitus there is pancreatic β cell damage caused by pro-inflammatory cytokines i.e interleukin-21 (IL-21). Black cumin seed oil (BCSO) contains antioxidants and immunomodulators but has not seen how it affects to IL-21. This study used cross over design to determine the effect of BCSO with dose of 1.5 mL/day and 3 mL/day dose of IL-21 in MS patients. The total subjects 66 of MS patients were divided into 2 groups. Group I was administered 1.5 mL/day and 3 mL/day of BCSO in dosage for 20 days and continued with washing out (BCSO discontinued) for 7 days. On the day 28, group I administrated 3 mL/day of BCSO and group II were given 1.5 mL/day of BCSO during 20 days. Statistical analysis showed that mean value expression of IL-21 were given by BCSO at dose 1.5 mL/day was 5.06±5.48 and BCSO at dose 3 mL/day 4.66±3.63 (p<0.05). The result showed that IL-21 expression in patient at risk of MS who received BCSO dose 3 mL/day were lower than those received adose of 1.5 mL/day for 20 days.

Preventive Effect of Pine Bark Extract (Flavangenol on Metabolic Disease in Western Diet-Loaded Tsumura Suzuki Obese Diabetes Mice

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Tsutomu Shimada

2011-01-01

Full Text Available It is known that the metabolic syndrome has a multi-factorial basis involving both genetic and environmental risk factors. In this study, Tsumura Suzuki Obese Diabetes (TSOD mice, a mouse model of multi-factorial, hereditary, obese type II diabetes, were given a Western diet (WTD as an environmental factor to prepare a disease model (TSOD-WTD and to investigate the preventive effects of Pine bark extract (Flavangenol against obesity and various features of metabolic disease appearing in this animal model. In contrast to control Tsumura Suzuki Non-obesity (TSNO mice, TSOD mice were obese and suffered from other metabolic complications. WTD-fed TSOD mice developed additional features such as hyperinsulinemia, abnormal glucose/lipid metabolism and fatty liver. The treatment with Flavangenol had a suppressive effect on increase in body weight and accumulation of visceral and subcutaneous fat, and also showed preventive effects on symptoms related to insulin resistance, abnormal glucose/lipid metabolism and hypertension. Flavangenol also increased the plasma concentration of adiponectin and decreased the plasma concentration of TNF-α. We next investigated the effect of Flavangenol on absorption of meal-derived lipids. Flavangenol suppressed absorption of neutral fat in an olive-oil-loading test (in vivo and showed an inhibitory effect on pancreatic lipase (in vitro. The above results suggest that Flavangenol has a preventive effect on severe metabolic disease due to multiple causes that involve both genetic and environmental risk factors. The mechanism of action might involve a partial suppressive effect of meal-derived lipids on absorption.

Melatonin: Action as antioxidant and potential applications in human disease and aging

International Nuclear Information System (INIS)

Bonnefont-Rousselot, Dominique; Collin, Fabrice

2010-01-01

This review aims at describing the beneficial properties of melatonin related to its antioxidant effects. Oxidative stress, i.e., an imbalance between the production of reactive oxygen species and antioxidant defences, is involved in several pathological conditions such as cardiovascular or neurological disease, and in aging. Therefore, research for antioxidants has developed. However, classical antioxidants often failed to exhibit beneficial effects, especially in metabolic diseases. Melatonin has been shown as a specific antioxidant due to its amphiphilic feature that allows it to cross physiological barriers, thereby reducing oxidative damage in both lipid and aqueous cell environments. Studies on the antioxidant action of melatonin are reported, with a special mention to water gamma radiolysis as a method to produce oxygen-derived free radicals, and on structure-activity relationships of melatonin derivatives. Mass spectrometry-based techniques have been developed to identify melatonin oxidation products. Besides its ability to scavenge several radical species, melatonin regulates the activity of antioxidant enzymes (indirect antioxidant properties). Efficient detection methods confirmed the presence of melatonin in several plant products. Therapeutic potential of melatonin relies either on increasing melatonin dietary intake or on supplementation with supraphysiological dosages. Clinical trials showed that melatonin could be efficient in preventing cell damage, as well under acute (sepsis, asphyxia in newborns) as under chronic (metabolic and neurodegenerative diseases, cancer, inflammation, aging). Its global action on oxidative stress, together with its rhythmicity that plays a role in several metabolic functions, lead melatonin to be of great interest for future clinical research in order to improve public health.

Short-time, high-dosage penicillin infusion therapy of syphilis

DEFF Research Database (Denmark)

Lomholt, Hans; Poulsen, Asmus; Brandrup, Flemming

2003-01-01

The optimal dosage and duration of penicillin treatment for the various stages of syphilis are not known. We present data on 20 patients with syphilis (primary, secondary or latent) treated with high-dose, short-time penicillin infusion therapy. Patients were given 10 MIU of penicillin G intraven......The optimal dosage and duration of penicillin treatment for the various stages of syphilis are not known. We present data on 20 patients with syphilis (primary, secondary or latent) treated with high-dose, short-time penicillin infusion therapy. Patients were given 10 MIU of penicillin G...

Spectrum analysis of common inherited metabolic diseases in Chinese patients screened and diagnosed by tandem mass spectrometry.

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Han, Lianshu; Han, Feng; Ye, Jun; Qiu, Wenjuan; Zhang, Huiwen; Gao, Xiaolan; Wang, Yu; Ji, Wenjun; Gu, Xuefan

2015-03-01

Information concerning inherited metabolic diseases in China is scarce. We investigated the prevalence and age distributions of amino acid, organic acid, and fatty acid oxidation disorders in Chinese patients. Blood levels of amino acids and acylcarnitines (tandem mass spectrometry) were measured in 18,303 patients with suspected inherited metabolic diseases. Diagnosis was based on clinical features, blood levels of amino acids or acylcarnitines, urinary organic acid levels (gas chromatography-mass spectrometry), and (in some) gene mutation tests. Inherited metabolic diseases were confirmed in 1,135 patients (739 males, 396 females). Median age was 12 months (1 day to 59 years). There were 28 diseases: 12 amino acid disorders (580 patients, 51.1%), with hyperphenylalaninemia (HPA) being the most common; nine organic acidemias (408 patients, 35.9%), with methylmalonic acidemia (MMA) as the most common; and seven fatty acid oxidation defects (147 patients, 13.0%), with multiple acyl-coenzyme A dehydrogenase deficiency (MADD) being the most common. Onset was mainly at 1-6 months for citrin deficiency, 0-6 months for MMA, and in newborns for ornithine transcarbamylase deficiency (OTCD). HPA was common in patients aged 1-3 years, and MADD was common in patients >18 years. In China, HPA, citrin deficiency, MMA, and MADD are the most common inherited disorders, particularly in newborns/infants. © 2014 Wiley Periodicals, Inc.

Non-alcoholic Fatty Liver Disease and Metabolic Syndrome in Hypopituitary Patients

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Nyenwe, Ebenezer A; Williamson-Baddorf, Sarah; Waters, Bradford; Wan, Jim Y; Solomon, Solomon S.

2009-01-01

Background Increased incidence of cardiovascular mortality and non-alcoholic fatty liver disease (NAFLD) has been reported in hypopituitarism; but previous studies did not correct for obesity in these patients. Therefore it remained unclear if endocrine deficiency in hypopituitarism is associated with metabolic consequences independent of obesity. This study was designed to determine the burden of cardiovascular disease and NAFLD in hypopituitarism. Methods We performed a retrospective case-control analysis of hypopituitary patients at Veterans Affair Medical center, Memphis; from January 1997- June 2007. After matching for age, gender, obesity and race, relevant data were abstracted from the subjects' records to determine the presence of hypopituitarism, cardiovascular risk factors and fatty liver disease. Cases and controls were characterized by descriptive statistics, and compared using Chi-square and Student's t- tests. Results Hypopituitary patients exhibited higher prevalence of hypertension- 88% vs 78% (P0.3). Hypopituitary patients had higher elevations in serum aminotransferase levels and hyperbilirubinemia-24% vs 11% (Phypopituitarism. Although hypopituitary patients had higher prevalence of cardiovascular risk factors than controls, they were not disproportionately affected by cardiovascular disease. PMID:19745609

Risk of development of chronic kidney disease in patients with type 2 diabetes having metabolic syndrome

International Nuclear Information System (INIS)

Moin, S.; Gondal, G.M.G.

2008-01-01

To measure the relation of creatinine clearance in type-2 diabetic patients with different components of metabolic syndrome and to quantify the relationship of frequency of incident CKD with increasing number of metabolic syndrome components while controlling for age, gender and duration of diabetes. Cross-sectional descriptive study. Patients having type-2 Diabetes for more than 5 years were enrolled. Information regarding age, gender, duration of diabetes, type of diabetes, treatment taking, complete fasting lipid profile, fasting blood glucose, Body Mass Index (BMI), 24 hours urinary proteins and creatinine clearance, co-existent risk factors like hypertension and ischemic heart disease was taken. Patients were divided into groups having one to all five metabolic syndrome traits. Progressive increase in the metabolic syndrome traits was compared with decline in creatinine clearance. Pearson correlation test and multiple logistic regression were applied to determine correlation with significance at r and p <0.05. Out of 104 evaluated female and male patients, 70% had hypertension, ischemic heart disease and a family history of diabetes. While 20% had normal creatinine clearance, 37% had a creatinine clearance between 60-90 ml/min, 19% had a creatinine clearance of 30-59 ml/min, 18% had a creatinine clearance of less than 30 ml/min and 10% were already in stage 5 CKD. The decline in renal function was more severe in subjects evaluated who had a higher number of features of the metabolic syndrome. Age was the only significant determinant of development of CKD (p=0.05). The renal function progressively declined with 3 or more features of the metabolic syndrome. (author)

Ferrokinetic Parameters and Regulation of Iron Metabolism in Patients with Chronic Inflammatory Bowel Diseases

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T.Y. Boiko

2014-11-01

Full Text Available Article presents parameters of iron metabolism and cytokines (IL-6 and TNF-α in patients with chronic inflammatory bowel diseases (CIBD. The material for the study was the blood of 69 patients with CIBD and anemia and 26 — without anemia. We have studied the features of main ferrokinetic parameters — iron, total iron-binding capacity of serum, transferrin saturation, ferritin, transferrin receptor, erythropoietin, hepcidin depending on hemoglobin level and the type of anemia. The relationship of iron metabolism disorders with the level of proinflammatory cytokines (IL-6 and TNF-α is shown.

Metabolic Syndrome and Chronic Renal Disease

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Vaia D. Raikou

2018-01-01

Full Text Available Background: The influence of metabolic syndrome (MetS on kidneys is related to many complications. We aimed to assess the association between MetS and chronic renal disease defined by a poor estimated glomerular filtration rate (eGFR and/or the presence of microalbuminuria/macroalbuminuria. Methods: 149 patients (77 males/72 females were enrolled in the study. Chronic renal disease was defined according to KDIGO 2012 criteria based on eGFR category and classified albuminuria. MetS was studied as a dichotomous variable (0 to 5 components including hypertension, waist circumference, low HDL-cholesterol, high triglycerides, and high glucose. Results: The association between clustering MetS and both classified eGFR and classified albuminuria (x2 = 50.3, p = 0.001 and x2 = 26.9, p = 0.003 respectively was found to be significant. The MetS presence showed an odds 5.3-fold (1.6–17.8 higher for low eGFR and 3.2-fold (1.2–8.8 higher for albuminuria in combination with the presence of diabetes mellitus, which also increased the risk for albuminuria by 3.5-fold (1.1–11.3. Albuminuria was significantly associated with high triglycerides, hypertension, high glucose (x2 = 11.8, p = 0.003, x2 = 11.4, p = 0.003 and x2 = 9.1, p = 0.01 respectively, and it was mildly associated with a low HDL-C (x2 = 5.7, p = 0.06. A significant association between classified eGFR and both high triglycerides and hypertension (x2 = 9.7, p = 0.04 and x2 = 16.1, p = 0.003 respectively was found. Conclusion: The clustering of MetS was significantly associated with chronic renal disease defined by both classified eGFR and albuminuria. The definition of impaired renal function by classified albuminuria was associated with more MetS components rather than the evaluation of eGFR category. MetS may contribute to the manifestation of albuminuria in patients with diabetes mellitus.

Sphingolipid Metabolism Correlates with Cerebrospinal Fluid Beta Amyloid Levels in Alzheimer’s Disease

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Fonteh, Alfred N.; Ormseth, Cora; Chiang, Jiarong; Cipolla, Matthew; Arakaki, Xianghong; Harrington, Michael G.

2015-01-01

Sphingolipids are important in many brain functions but their role in Alzheimer’s disease (AD) is not completely defined. A major limit is availability of fresh brain tissue with defined AD pathology. The discovery that cerebrospinal fluid (CSF) contains abundant nanoparticles that include synaptic vesicles and large dense core vesicles offer an accessible sample to study these organelles, while the supernatant fluid allows study of brain interstitial metabolism. Our objective was to characterize sphingolipids in nanoparticles representative of membrane vesicle metabolism, and in supernatant fluid representative of interstitial metabolism from study participants with varying levels of cognitive dysfunction. We recently described the recruitment, diagnosis, and CSF collection from cognitively normal or impaired study participants. Using liquid chromatography tandem mass spectrometry, we report that cognitively normal participants had measureable levels of sphingomyelin, ceramide, and dihydroceramide species, but that their distribution differed between nanoparticles and supernatant fluid, and further differed in those with cognitive impairment. In CSF from AD compared with cognitively normal participants: a) total sphingomyelin levels were lower in nanoparticles and supernatant fluid; b) levels of ceramide species were lower in nanoparticles and higher in supernatant fluid; c) three sphingomyelin species were reduced in the nanoparticle fraction. Moreover, three sphingomyelin species in the nanoparticle fraction were lower in mild cognitive impairment compared with cognitively normal participants. The activity of acid, but not neutral sphingomyelinase was significantly reduced in the CSF from AD participants. The reduction in acid sphingomylinase in CSF from AD participants was independent of depression and psychotropic medications. Acid sphingomyelinase activity positively correlated with amyloid β42 concentration in CSF from cognitively normal but not impaired

Genetic basis for dosage sensitivity in Arabidopsis thaliana.

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Isabelle M Henry

2007-04-01

Full Text Available Aneuploidy, the relative excess or deficiency of specific chromosome types, results in gene dosage imbalance. Plants can produce viable and fertile aneuploid individuals, while most animal aneuploids are inviable or developmentally abnormal. The swarms of aneuploid progeny produced by Arabidopsis triploids constitute an excellent model to investigate the mechanisms governing dosage sensitivity and aneuploid syndromes. Indeed, genotype alters the frequency of aneuploid types within these swarms. Recombinant inbred lines that were derived from a triploid hybrid segregated into diploid and tetraploid individuals. In these recombinant inbred lines, a single locus, which we call SENSITIVE TO DOSAGE IMBALANCE (SDI, exhibited segregation distortion in the tetraploid subpopulation only. Recent progress in quantitative genotyping now allows molecular karyotyping and genetic analysis of aneuploid populations. In this study, we investigated the causes of the ploidy-specific distortion at SDI. Allele frequency was distorted in the aneuploid swarms produced by the triploid hybrid. We developed a simple quantitative measure for aneuploidy lethality and using this measure demonstrated that distortion was greatest in the aneuploids facing the strongest viability selection. When triploids were crossed to euploids, the progeny, which lack severe aneuploids, exhibited no distortion at SDI. Genetic characterization of SDI in the aneuploid swarm identified a mechanism governing aneuploid survival, perhaps by buffering the effects of dosage imbalance. As such, SDI could increase the likelihood of retaining genomic rearrangements such as segmental duplications. Additionally, in species where triploids are fertile, aneuploid survival would facilitate gene flow between diploid and tetraploid populations via a triploid bridge and prevent polyploid speciation. Our results demonstrate that positional cloning of loci affecting traits in populations containing ploidy and

Effect of folic acid on methionine and homocysteine metabolism in end-stage renal disease

NARCIS (Netherlands)

Stam, F.; van Guldener, C.; ter Wee, P.M.; Jakobs, C.A.J.M.; van der Meer, K.; Stehouwer, C.D.A.

2005-01-01

Background. The pathogenesis of hyperhomocysteinemia in end-stage renal disease (ESRD) is unclear. Folic acid lowers, but does not normalize, the plasma homocysteine level in patients with ESRD, but its effect on whole body metabolism of homocysteine is unknown. Methods We studied the effect of 3

Paradigm shift in cancer treatment: Cancer treatment as a metabolic disease – fusion of Eastern and Western medicine

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Reo Hamaguchi

2017-10-01

Full Text Available Current standard therapies for cancer, including surgery, anti-cancer drugs, and radiotherapy, are thought to contribute to the improvement in the survival rates of cancer patients. However, such standard therapies have 3 major problems: in advanced cancers, it is unlikely that standard cancer treatments will cure the disease; adverse side effects that accompany standard cancer treatments put many patients in distress; and a large amount of medical expenditure is required for new and expensive anti-cancer drugs. These problems may be viewed as a result of establishing treatments without any consideration regarding the root cause of the cancer. Otto Warburg suggested that particular changes in the energy metabolism of cells, which are associated with a shortage of oxygen, are the root cause of cancer. Cancer cells have unique metabolic characteristics, and thus we believe that it is important to treat cancer as a metabolic disease. More specifically, not only is it important to suppress cancer cell metabolism, but it is also important to improve the chronic inflammation that is associated with the development and progression of cancer, and to support the functions of immune cells. This type of view of cancer treatment coincides with the principles of Chinese medicine, which has a history of 4000 years, such as “fuzheng quxie” and “zhibing qiuben”, which can assist in the establishment of cancer treatments for patients. In this article, we discuss cancer treatments from the view of cancer as a metabolic disease and their association with Chinese medicine, and introduce some clinical cases along with a review of the literature.

The Role of Peroxisome Proliferator-Activated Receptor β/δ on the Inflammatory Basis of Metabolic Disease

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Teresa Coll

2010-01-01

Full Text Available The pathophysiology underlying several metabolic diseases, such as obesity, type 2 diabetes mellitus, and atherosclerosis, involves a state of chronic low-level inflammation. Evidence is now emerging that the nuclear receptor Peroxisome Proliferator-Activated Receptor (PPARβ/δ ameliorates these pathologies partly through its anti-inflammatory effects. PPARβ/δ activation prevents the production of inflammatory cytokines by adipocytes, and it is involved in the acquisition of the anti-inflammatory phenotype of macrophages infiltrated in adipose tissue. Furthermore, PPARβ/δ ligands prevent fatty acid-induced inflammation in skeletal muscle cells, avoid the development of cardiac hypertrophy, and suppress macrophage-derived inflammation in atherosclerosis. These data are promising and suggest that PPARβ/δ ligands may become a therapeutic option for preventing the inflammatory basis of metabolic diseases.

The medical food Souvenaid affects brain phospholipid metabolism in mild Alzheimer's disease: results from a randomized controlled trial.

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Rijpma, Anne; van der Graaf, Marinette; Lansbergen, Marieke M; Meulenbroek, Olga; Cetinyurek-Yavuz, Aysun; Sijben, John W; Heerschap, Arend; Olde Rikkert, Marcel G M

2017-07-26

Synaptic dysfunction contributes to cognitive impairment in Alzheimer's disease and may be countered by increased intake of nutrients that target brain phospholipid metabolism. In this study, we explored whether the medical food Souvenaid affects brain phospholipid metabolism in patients with Alzheimer's disease. Thirty-four drug-naive patients with mild Alzheimer's disease (Mini Mental State Examination score ≥20) were enrolled in this exploratory, double-blind, randomized controlled study. Before and after 4-week intervention with Souvenaid or an isocaloric control product, phosphorus and proton magnetic resonance spectroscopy (MRS) was performed to assess surrogate measures of phospholipid synthesis and breakdown (phosphomonoesters [PME] and phosphodiesters [PDEs]), neural integrity (N-acetyl aspartate), gliosis (myo-inositol), and choline metabolism (choline-containing compounds [tCho]). The main outcome parameters were PME and PDE signal intensities and the PME/PDE ratio. MRS data from 33 patients (60-86 years old; 42% males; Souvenaid arm n = 16; control arm n = 17) were analyzed. PME/PDE and tCho were higher after 4 weeks of Souvenaid compared with control (PME/PDE least squares [LS] mean difference [95% CI] 0.18 [0.06-0.30], p = 0.005; tCho LS mean difference [95% CI] 0.01 [0.00-0.02], p = 0.019). No significant differences were observed in the other MRS outcome parameters. MRS reveals that Souvenaid affects brain phospholipid metabolism in mild Alzheimer's disease, in line with findings in preclinical studies. Netherlands Trial Register, NTR3346 . Registered on 13 March 2012.

Thermodynamics in Neurodegenerative Diseases: Interplay Between Canonical WNT/Beta-Catenin Pathway-PPAR Gamma, Energy Metabolism and Circadian Rhythms.

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Vallée, Alexandre; Lecarpentier, Yves; Guillevin, Rémy; Vallée, Jean-Noël

2018-03-23

Entropy production rate is increased by several metabolic and thermodynamics abnormalities in neurodegenerative diseases (NDs). Irreversible processes are quantified by changes in the entropy production rate. This review is focused on the opposing interactions observed in NDs between the canonical WNT/beta-catenin pathway and PPAR gamma and their metabolic and thermodynamic implications. In amyotrophic lateral sclerosis and Huntington's disease, WNT/beta-catenin pathway is upregulated, whereas PPAR gamma is downregulated. In Alzheimer's disease and Parkinson's disease, WNT/beta-catenin pathway is downregulated while PPAR gamma is upregulated. The dysregulation of the canonical WNT/beta-catenin pathway is responsible for the modification of thermodynamics behaviors of metabolic enzymes. Upregulation of WNT/beta-catenin pathway leads to aerobic glycolysis, named Warburg effect, through activated enzymes, such as glucose transporter (Glut), pyruvate kinase M2 (PKM2), pyruvate dehydrogenase kinase 1(PDK1), monocarboxylate lactate transporter 1 (MCT-1), lactic dehydrogenase kinase-A (LDH-A) and inactivation of pyruvate dehydrogenase complex (PDH). Downregulation of WNT/beta-catenin pathway leads to oxidative stress and cell death through inactivation of Glut, PKM2, PDK1, MCT-1, LDH-A but activation of PDH. In addition, in NDs, PPAR gamma is dysregulated, whereas it contributes to the regulation of several key circadian genes. NDs show many dysregulation in the mediation of circadian clock genes and so of circadian rhythms. Thermodynamics rhythms operate far-from-equilibrium and partly regulate interactions between WNT/beta-catenin pathway and PPAR gamma. In NDs, metabolism, thermodynamics and circadian rhythms are tightly interrelated.

Microbial pathways in colonic sulfur metabolism and links with health and disease

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Franck eCarbonero

2012-11-01

Full Text Available Sulfur is both crucial to life and a potential threat to health. While colonic sulfur metabolism mediated by eukaryotic cells is relatively well studied, much less is known about sulfur metabolism within gastrointestinal microbes. Sulfated compounds in the colon are either of inorganic (e.g., sulfates, sulfites or organic (e.g., dietary amino acids and host mucins origin. The most extensively studied of the microbes involved in colonic sulfur metabolism are the sulfate-reducing bacteria, which are common colonic inhabitants. Many other microbial pathways are likely to shape colonic sulfur metabolism as well as the composition and availability of sulfated compounds, and these interactions need to be examined in more detail. Hydrogen sulfide is the sulfur derivative that has attracted the most attention in the context of colonic health, and the extent to which it is detrimental or beneficial remains in debate. Several lines of evidence point to sulfate-reducing bacteria or exogenous hydrogen sulfide as potential players in the etiology of intestinal disorders, inflammatory bowel diseases and colorectal cancer in particular. Generation of hydrogen sulfide via pathways other than dissimilatory sulfate reduction may be as, or more, important than those involving the sulfate-reducing bacteria. We suggest here that a novel axis of research is to assess the effects of hydrogen sulfide in shaping colonic microbiome structure. Clearly, in-depth characterization of the microbial pathways involved in colonic sulfur metabolism is necessary for a better understanding of its contribution to colonic disorders and development of therapeutic strategies.

Nano-Calorimetry based point of care biosensor for metabolic disease management.

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Kazura, Evan; Lubbers, Brad R; Dawson, Elliott; Phillips, John A; Baudenbacher, Franz

2017-09-01

Point of care (POC) diagnostics represents one of the fastest growing health care technology segments. Developments in microfabrication have led to the development of highly-sensitive nanocalorimeters ideal for directly measuring heat generated in POC biosensors. Here we present a novel nano-calorimeter-based biosensor design with differential sensing to eliminate common mode noise and capillary microfluidic channels for sample delivery to the thermoelectric sensor. The calorimeter has a resolution of 1.4 ± 0.2 nJ/(Hz) 1/2 utilizing a 27 junction bismuth/titanium thermopile, with a total Seebeck coefficient of 2160 μV/K. Sample is wicked to the calorimeter through a capillary channel making it suitable for monitoring blood obtained through a finger prick (performance in a model assay using catalase, achieving a threshold for hydrogen peroxide quantification of 50 μM. The potential for our device as a POC blood test for metabolic diseases is shown through the quantification of phenylalanine (Phe) in serum, an unmet necessary service in the management of Phenylketonuria (PKU). Pegylated phenylalanine ammonia-lyase (PEG-PAL) was utilized to react with Phe, but reliable detection was limited to <5 mM due to low enzymatic activity. The POC biosensor concept can be multiplexed and adapted to a large number of metabolic diseases utilizing different immobilized enzymes.

Administered activity of Tc-99m MDP for bone scintigraphy, standard or individual dosage?

International Nuclear Information System (INIS)

Vestergren, E.; Gretarsdottir, J.; Jacobsson, L.

2002-01-01

Background and Aim: Adult patients are generally, irrespective of size, given the same amount of activity for a certain type of nuclear medicine examination, a standard dosage. Identical image quality is essential when comparing different patient studies. The aim of this study is to evaluate different dosage methods for Tc-99m-MDP bone scintigraphy and to investigate whether individual dosage will decrease the variations in image quality between different patients. Material and Methods: 100 consecutive adult patients (aged between 40 and 89 years) undergoing whole body bone scintigraphy were studied. Eight patients were excluded from the study because of abnormal high uptake in the areas of interest. The patient weight and height were registered. The activity in the syringes was measured before and after the injection of about 600 MBq Tc-99m MDP. Scanning was performed, with a dual head gamma camera (Maxxus or Millennium VG, General Electric) equipped with a high-resolution collimator, at approximately 4 hours (mean 3.8 h) post-injection. Regions of interest (ROI) were drawn over the lumbar spine (posterior view), the right femur (anterior view) and also soft tissue background regions for each area. The total counts, maximum counts/pixel and number of pixels in the ROIs were registered. The maximum number of counts/pixel (background-subtracted), SPINEmax and FEMURmax were chosen as the image quality parameters. For each patient, SPINEmax and FEMURmax where recalculated to the number that would have been obtained with standard dosage (exactly 600 MBq), and dosage proportional to body weight, body surface area and body height. All values were corrected to a scanning time 3.8 h after injection. Results: Both with a standard activity dosage and a dosage proportional to body height, SPINEmax decreases with increasing body weight. Dosage proportional to body weight gives increasing values of SPINEmax with increasing body weight. Dosage proportional to body surface area

Cardiometabolic disease risk in metabolically healthy and unhealthy obesity: Stability of metabolic health status in adults.

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Guo, Fangjian; Garvey, W Timothy

2016-02-01

To assess the stability of metabolic status and body mass index (BMI) status and their relative contribution to risk of diabetes, cardiovascular events, and mortality. A total of 14,685 participants from the Atherosclerosis Risk in Communities Study and 4,990 from the Coronary Artery Risk Development in Young Adults Study were included. People with healthy obesity (HO) are defined as those meeting all three indices of blood pressure, blood glucose, and blood lipids. People with unhealthy obesity crossed the risk threshold for all three criteria. In both healthy and unhealthy subgroups, risks for coronary heart disease (CHD), stroke, and mortality were comparable among BMI status during a mean 18.7-year follow-up. When compared with HO, hazard ratios were increased for diabetes (5.56, 95% confidence interval [CI] 4.12-7.48), CHD (5.60, 95% CI 3.14-9.98), stroke (4.84, 95% CI 2.13-10.97), and mortality (2.6, 95% CI 1.88-3.61) in people with unhealthy obesity. BMI only moderately increased the risks for diabetes among healthy subjects. In the Coronary Artery Risk Development in Young Adults Study over 20 years, 17.5% of lean subjects and 67.3% of overweight subjects at baseline developed obesity during follow-up. Despite rising BMI, metabolic status remained relatively stable. Metabolic status is relatively stable despite rising BMI. HO had lower risks for diabetes, CHD, stroke, and mortality than unhealthy subjects but increased diabetes risks than healthy lean people. Cardiometabolic risk factors confer much higher risk than obesity per se. © 2015 The Obesity Society.

Endocrine Disrupting Chemical Induced "Pollution of Metabolic Pathways": A Case of Shifting Paradigms With Implications for Vascular Diseases.

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Janardhanan, Rajiv

2018-05-14

The latter half of the twentieth century has witnessed a humongous spurt in the use of synthetic chemicals in a wide variety of industrial and agricultural applications are leading to niche specific perturbations affecting every trophic level of the ecosystems due to unmitigated environmental contamination. Despite the incremental usefulness of endocrine disrupting chemicals (EDCs) such as pesticides and plasticizers, their statutory impact on environmental health is assuming worrisome proportions. The EDCs can disrupt physiological homeostasis resulting in developmental and reproductive abnormalities. Both preclinical animal experiments, as well as epidemiological studies, have correlated EDC exposure with metabolic disorders such as metabolic syndrome, type 2 diabetes as well as cardiovascular health. Here we briefly review the statutory impact of EDCs on metabolic disruption as well as their impact on environmental health. Finally, difficulties pertaining to the categorization of EDC induced metabolic diseases as risk factors for global disease burden have been addressed taking into account the complexity of such interactions. Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.org.

Inherent lipid metabolic dysfunction in glycogen storage disease IIIa.

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Li, Xin-Hua; Gong, Qi-Ming; Ling, Yun; Huang, Chong; Yu, De-Min; Gu, Lei-Lei; Liao, Xiang-Wei; Zhang, Dong-Hua; Hu, Xi-Qi; Han, Yue; Kong, Xiao-Fei; Zhang, Xin-Xin

2014-12-05

We studied two patients from a nonconsanguineous family with life-long abnormal liver function, hepatomegaly and abnormal fatty acid profiles. Abnormal liver function, hypoglycemia and muscle weakness are observed in various genetic diseases, including medium-chain acyl-CoA dehydrogenase (MCAD) deficiency and glycogen storage diseases. The proband showed increased free fatty acids, mainly C8 and C10, resembling fatty acid oxidation disorder. However, no mutation was found in ACADM and ACADL gene. Sequencing of theamylo-alpha-1, 6-glucosidase, 4-alpha-glucanotransferase (AGL) gene showed that both patients were compound heterozygotes for c.118C > T (p.Gln40X) and c.753_756 del CAGA (p.Asp251Glufsx29), whereas their parents were each heterozygous for one of these mutations. The AGL protein was undetectable in EBV-B cells from the two patients. Transcriptome analysis demonstrated a significant different pattern of gene expression in both of patients’ cells, including genes involving in the PPAR signaling pathway, fatty acid biosynthesis, lipid synthesis and visceral fat deposition and metabolic syndrome. This unique gene expression pattern is probably due to the absence of AGL, which potentially accounts for the observed clinical phenotypes of hyperlipidemia and hepatocyte steatosis in glycogen storage disease type IIIa.

Neuronal and astrocytic metabolism in a transgenic rat model of Alzheimer's disease.

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Nilsen, Linn Hege; Witter, Menno P; Sonnewald, Ursula

2014-05-01

Regional hypometabolism of glucose in the brain is a hallmark of Alzheimer's disease (AD). However, little is known about the specific alterations of neuronal and astrocytic metabolism involved in homeostasis of glutamate and GABA in AD. Here, we investigated the effects of amyloid β (Aβ) pathology on neuronal and astrocytic metabolism and glial-neuronal interactions in amino acid neurotransmitter homeostasis in the transgenic McGill-R-Thy1-APP rat model of AD compared with healthy controls at age 15 months. Rats were injected with [1-(13)C]glucose and [1,2-(13)C]acetate, and extracts of the hippocampal formation as well as several cortical regions were analyzed using (1)H- and (13)C nuclear magnetic resonance spectroscopy and high-performance liquid chromatography. Reduced tricarboxylic acid cycle turnover was evident for glutamatergic and GABAergic neurons in hippocampal formation and frontal cortex, and for astrocytes in frontal cortex. Pyruvate carboxylation, which is necessary for de novo synthesis of amino acids, was decreased and affected the level of glutamine in hippocampal formation and those of glutamate, glutamine, GABA, and aspartate in the retrosplenial/cingulate cortex. Metabolic alterations were also detected in the entorhinal cortex. Overall, perturbations in energy- and neurotransmitter homeostasis, mitochondrial astrocytic and neuronal metabolism, and aspects of the glutamate-glutamine cycle were found in McGill-R-Thy1-APP rats.

Impact of type 2 diabetes and the metabolic syndrome on myocardial structure and microvasculature of men with coronary artery disease

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Yii Michael

2011-09-01

Full Text Available Abstract Background Type 2 diabetes and the metabolic syndrome are associated with impaired diastolic function and increased heart failure risk. Animal models and autopsy studies of diabetic patients implicate myocardial fibrosis, cardiomyocyte hypertrophy, altered myocardial microvascular structure and advanced glycation end-products (AGEs in the pathogenesis of diabetic cardiomyopathy. We investigated whether type 2 diabetes and the metabolic syndrome are associated with altered myocardial structure, microvasculature, and expression of AGEs and receptor for AGEs (RAGE in men with coronary artery disease. Methods We performed histological analysis of left ventricular biopsies from 13 control, 10 diabetic and 23 metabolic syndrome men undergoing coronary artery bypass graft surgery who did not have heart failure or atrial fibrillation, had not received loop diuretic therapy, and did not have evidence of previous myocardial infarction. Results All three patient groups had similar extent of coronary artery disease and clinical characteristics, apart from differences in metabolic parameters. Diabetic and metabolic syndrome patients had higher pulmonary capillary wedge pressure than controls, and diabetic patients had reduced mitral diastolic peak velocity of the septal mitral annulus (E', consistent with impaired diastolic function. Neither diabetic nor metabolic syndrome patients had increased myocardial interstitial fibrosis (picrosirius red, or increased immunostaining for collagen I and III, the AGE Nε-(carboxymethyllysine, or RAGE. Cardiomyocyte width, capillary length density, diffusion radius, and arteriolar dimensions did not differ between the three patient groups, whereas diabetic and metabolic syndrome patients had reduced perivascular fibrosis. Conclusions Impaired diastolic function of type 2 diabetic and metabolic syndrome patients was not dependent on increased myocardial fibrosis, cardiomyocyte hypertrophy, alteration of the

Dependence of surface smoothing, sputtering and etching phenomena on cluster ion dosage

CERN Document Server

Song, J H; Choi, W K

2002-01-01

The dependence of surface smoothing and sputtering phenomena of Si (1 0 0) solid surfaces irradiated by CO sub 2 cluster ions on cluster-ion dosage was investigated using an atomic force microscope. The flux and total ion dosage of impinging cluster ions at the acceleration voltage of 50 kV were fixed at 10 sup 9 ions/cm sup 2 s and were scanned from 5x10 sup 1 sup 0 to 5x10 sup 1 sup 3 ions/cm sup 2 , respectively. The density of hillocks induced by cluster ion impact was gradually increased with the dosage up to 5x10 sup 1 sup 1 ions/cm sup 2 , which caused that the irradiated surface became rough from 0.4 to 1.24 nm in root-mean-square roughness (sigma sub r sub m sub s). At the boundary of the ion dosage of 10 sup 1 sup 2 ions/cm sup 2 , the density of the induced hillocks was decreased and sigma sub r sub m sub s was about 1.21 nm, not being deteriorated further. At the dosage of 5x10 sup 1 sup 3 ions/cm sup 2 , the induced hillocks completely disappeared and the surface became very flat as much as sigma...

Metabolic syndrome and menopause

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Jouyandeh Zahra

2013-01-01

Full Text Available Abstract Background The metabolic syndrome is defined as an assemblage of risk factors for cardiovascular diseases, and menopause is associated with an increase in metabolic syndrome prevalence. The aim of this study was to assess the prevalence of metabolic syndrome and its components among postmenopausal women in Tehran, Iran. Methods In this cross-sectional study in menopause clinic in Tehran, 118 postmenopausal women were investigated. We used the adult treatment panel 3 (ATP3 criteria to classify subjects as having metabolic syndrome. Results Total prevalence of metabolic syndrome among our subjects was 30.1%. Waist circumference, HDL-cholesterol, fasting blood glucose, diastolic blood pressure ,Systolic blood pressure, and triglyceride were significantly higher among women with metabolic syndrome (P-value Conclusions Our study shows that postmenopausal status is associated with an increased risk of metabolic syndrome. Therefore, to prevent cardiovascular disease there is a need to evaluate metabolic syndrome and its components from the time of the menopause.

Measuring Glial Metabolism in Repetitive Brain Trauma and Alzheimer’s Disease

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2016-09-01

stages of repetitive brain trauma as well. Current methods of measure brain glutamate using proton spectroscopy is not specific to different cell...covering a representative range of clinical cases: a young female , young male , middle-aged male (all healthy volunteers) and a male patient with...AWARD NUMBER: W81XWH-15-1-0412 TITLE: Measuring Glial Metabolism in Repetitive Brain Trauma and Alzheimer’s Disease PRINCIPAL INVESTIGATOR

Fatty liver associated with metabolic derangement in patients with chronic kidney disease: A controlled attenuation parameter study

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Chang-Yun Yoon

2017-03-01

Full Text Available Background: Hepatic steatosis measured with controlled attenuation parameter (CAP using transient elastography predicts metabolic syndrome in the general population. We investigated whether CAP predicted metabolic syndrome in chronic kidney disease patients. Methods: CAP was measured with transient elastography in 465 predialysis chronic kidney disease patients (mean age, 57.5 years. Results: The median CAP value was 239 (202–274 dB/m. In 195 (41.9% patients with metabolic syndrome, diabetes mellitus was more prevalent (105 [53.8%] vs. 71 [26.3%], P < 0.001, with significantly increased urine albumin-to-creatinine ratio (184 [38–706] vs. 56 [16–408] mg/g Cr, P = 0.003, high sensitivity C-reactive protein levels (5.4 [1.4–28.2] vs. 1.7 [0.6–9.9] mg/L, P < 0.001, and CAP (248 [210–302] vs. 226 [196–259] dB/m, P < 0.001. In multiple linear regression analysis, CAP was independently related to body mass index (β = 0.742, P < 0.001, triglyceride levels (β = 2.034, P < 0.001, estimated glomerular filtration rate (β = 0.316, P = 0.001, serum albumin (β = 1.386, P < 0.001, alanine aminotransferase (β = 0.064, P = 0.029, and total bilirubin (β = −0.881, P = 0.009. In multiple logistic regression analysis, increased CAP was independently associated with increased metabolic syndrome risk (per 10 dB/m increase; odds ratio, 1.093; 95% confidence interval, 1.009–1.183; P = 0.029 even after adjusting for multiple confounding factors. Conclusion: Increased CAP measured with transient elastography significantly correlated with and could predict increased metabolic syndrome risk in chronic kidney disease patients.