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Sample records for adult metabolic disease

  1. Metabolic aspects of adult patients with nonalcoholic fatty liver disease.

    PubMed

    Abenavoli, Ludovico; Milic, Natasa; Di Renzo, Laura; Preveden, Tomislav; Medić-Stojanoska, Milica; De Lorenzo, Antonino

    2016-08-21

    Nonalcoholic fatty liver disease (NAFLD) is a major cause of chronic liver disease and it encompasses a spectrum from simple steatosis to steatohepatitis, fibrosis, or cirrhosis. The mechanisms involved in the occurrence of NAFLD and its progression are probably due to a metabolic profile expressed within the context of a genetic predisposition and is associated with a higher energy intake. The metabolic syndrome (MS) is a cluster of metabolic alterations associated with an increased risk for the development of cardiovascular diseases and diabetes. NAFLD patients have more than one feature of the MS, and now they are considered the hepatic components of the MS. Several scientific advances in understanding the association between NAFLD and MS have identified insulin resistance (IR) as the key aspect in the pathophysiology of both diseases. In the multi parallel hits theory of NAFLD pathogenesis, IR was described to be central in the predisposition of hepatocytes to be susceptible to other multiple pathogenetic factors. The recent knowledge gained from these advances can be applied clinically in the prevention and management of NAFLD and its associated metabolic changes. The present review analyses the current literature and highlights the new evidence on the metabolic aspects in the adult patients with NAFLD. PMID:27610012

  2. Metabolic aspects of adult patients with nonalcoholic fatty liver disease

    PubMed Central

    Abenavoli, Ludovico; Milic, Natasa; Di Renzo, Laura; Preveden, Tomislav; Medić-Stojanoska, Milica; De Lorenzo, Antonino

    2016-01-01

    Nonalcoholic fatty liver disease (NAFLD) is a major cause of chronic liver disease and it encompasses a spectrum from simple steatosis to steatohepatitis, fibrosis, or cirrhosis. The mechanisms involved in the occurrence of NAFLD and its progression are probably due to a metabolic profile expressed within the context of a genetic predisposition and is associated with a higher energy intake. The metabolic syndrome (MS) is a cluster of metabolic alterations associated with an increased risk for the development of cardiovascular diseases and diabetes. NAFLD patients have more than one feature of the MS, and now they are considered the hepatic components of the MS. Several scientific advances in understanding the association between NAFLD and MS have identified insulin resistance (IR) as the key aspect in the pathophysiology of both diseases. In the multi parallel hits theory of NAFLD pathogenesis, IR was described to be central in the predisposition of hepatocytes to be susceptible to other multiple pathogenetic factors. The recent knowledge gained from these advances can be applied clinically in the prevention and management of NAFLD and its associated metabolic changes. The present review analyses the current literature and highlights the new evidence on the metabolic aspects in the adult patients with NAFLD. PMID:27610012

  3. Metabolic aspects of adult patients with nonalcoholic fatty liver disease

    PubMed Central

    Abenavoli, Ludovico; Milic, Natasa; Di Renzo, Laura; Preveden, Tomislav; Medić-Stojanoska, Milica; De Lorenzo, Antonino

    2016-01-01

    Nonalcoholic fatty liver disease (NAFLD) is a major cause of chronic liver disease and it encompasses a spectrum from simple steatosis to steatohepatitis, fibrosis, or cirrhosis. The mechanisms involved in the occurrence of NAFLD and its progression are probably due to a metabolic profile expressed within the context of a genetic predisposition and is associated with a higher energy intake. The metabolic syndrome (MS) is a cluster of metabolic alterations associated with an increased risk for the development of cardiovascular diseases and diabetes. NAFLD patients have more than one feature of the MS, and now they are considered the hepatic components of the MS. Several scientific advances in understanding the association between NAFLD and MS have identified insulin resistance (IR) as the key aspect in the pathophysiology of both diseases. In the multi parallel hits theory of NAFLD pathogenesis, IR was described to be central in the predisposition of hepatocytes to be susceptible to other multiple pathogenetic factors. The recent knowledge gained from these advances can be applied clinically in the prevention and management of NAFLD and its associated metabolic changes. The present review analyses the current literature and highlights the new evidence on the metabolic aspects in the adult patients with NAFLD.

  4. Endocrine manifestations related to inherited metabolic diseases in adults

    PubMed Central

    2012-01-01

    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. PMID:22284844

  5. Prevalence of chronic kidney disease in adults with metabolic syndrome.

    PubMed

    Emem-Chioma, P C; Siminialayi, I M; Wokoma, F S

    2011-09-01

    The burden of chronic kidney disease (CKD) and other non- communicable diseases continues to rise globally, and recent studies suggest that metabolic syndrome (MS) may add to this burden by contributing to the development of CKD. Given that reports on the prevalence of CKD in patients with MS in this environment are scanty, this study was undertaken with the sole aim of determining the prevalence of CKD in subjects with MS as defined by the International Diabetes Federation (IDF) and the National Cholesterol Education Project Adult Treatment Panel III (NCEP ATP III). A total of 240 consenting adults (18-70 years) attending the general out- patient clinic of the General Hospital Okrika for various ailments were studied. Subjects were screened for MS as per the above- mentioned criteria. Estimated GFR (eGFR) was determined with Modification of Diet for Renal Disease (MDRD) formula and CKD was defined as eGFR less than 60 mL/min/1.73 m2 . Data was analyzed using SPSS version 12.0 and Epi info version 4.06d; P <0.05 was considered as significant. A total of 88 males and 152 females were screened for MS by both criteria. Eighty- four (35.0%) of 240 subjects had MS as defined by NCEP ATP III, while 85 (35.4%) had MS as defined by the IDF. The subjects were predominantly females, and mean age was between 54.74 ± 15.30 and 55.60 ± 14.81 years. Four of the 84 (4.8%) subjects with MS by NCEP ATP III definition had CKD while three of the 85 (3.5%) subjects with MS by IDF definition had CKD. Among subjects without MS by either definition, the prevalence of CKD was four of 140 (2.9%). Although the prevalence of CKD was higher among subjects with MS by ATP III compared with those with MS as defined by IDF and subjects without MS, the differences were not statistically significant (X2 = 0.14; P = 0.710). A comparison of MS subjects without CKD and those with CKD did not show any significant difference in age, waist circumference, body mass index, blood pressure, fasting blood

  6. Bone and mineral metabolism in adult celiac disease

    SciTech Connect

    Caraceni, M.P.; Molteni, N.; Bardella, M.T.; Ortolani, S.; Nogara, A.; Bianchi, P.A.

    1988-03-01

    Bone mineral density (/sup 125/I photon absorptiometry) was lower in 20 untreated adult celiac patients than in sex- and age-matched controls (p less than 0.001), and plasma alkaline phosphatase, parathyroid hormone, urinary hydroxyproline/creatinine levels were higher than normal (p less than 0.05, less than 0.001, less than 0.05, respectively). Gluten-free diet was started, and the patients were divided randomly into two treatment groups, one which received oral 25-hydroxyvitamin D 50 micrograms/day and one which did not. After 12 months' treatment, bone turnover markers showed a decrease, which did not reach statistical significance, and bone mineral density did not show significant modifications compared with base line in either group. It was found that a gluten-free diet followed for 1 yr can prevent further bone loss, but no significant differences were detected between the two groups.

  7. Energy Metabolism, Adult Neurogenesis and their Possible Roles in Alzheimer's Disease: A Brief Overview.

    PubMed

    Sun, Ping; Hua, Qian; Schmitt, Angelika G

    2016-01-01

    Alzheimer's disease (AD) is the most prevalent human neurodegenerative disease. Disturbances of brain glucose uptake, glucose tolerance, glucose utilization and of the insulin/insulin receptor signaling cascade are thought to be key features of the pathophysiology of AD. Changes in energy homeostasis in the brain and in the periphery dramatically influence the proliferation of adult neural stem cells and neurogenesis in the hippocampus. Recent findings suggest that adult neurogenesis is altered in the hippocampus of AD patients and in various animal models of AD. Several factors associated with the pathogenesis of AD are also known to be involved in the regulation of adult neurogenesis. Understanding the mechanisms underlying these changes at different stages of AD could provide insights into its pathogenesis, contribute to identifying biomarkers of early AD, and supply fundamental knowledge that will allow novel therapeutic approaches to treating AD by intervening in adult neurogenesis. In this review we provide an overview of the connections between energy metabolism, adult neurogenesis and AD.

  8. Prevalence of Central Obesity among Adults with Normal BMI and Its Association with Metabolic Diseases in Northeast China

    PubMed Central

    Zhang, Peng; Wang, Rui; Gao, Chunshi; Jiang, Lingling; Lv, Xin; Song, Yuanyuan; Li, Bo

    2016-01-01

    Objectives The present study aimed to investigate the prevalence of central obesity among adults with normal BMI and its association with metabolic diseases in Jilin Province, China. Methods A population-based cross-sectional study was conducted in 2012 in Jilin Province of China. Information was collected by face to face interview. Descriptive data analysis and 95% confidence intervals (CI) of prevalence/frequency were conducted. Log-binomial regression analyses were used to find the independent factors associated with central obesity and to explore the adjusted association between central obesity and metabolic diseases among adults with normal BMI. Results Among the adult residents with normal BMI in Jilin Province, 55.6% of participants with central obesity self-assessed as normal weight and 27.0% thought their body weight were above normal. 12.7% of central obesity people took methods to lose weight, while 85.3% didn’t. Female, older people and non-manual worker had higher risk to be central obesity among adults with normal BMI. Hypertension, diabetes and hyperlipidemia were significantly associated with central obesity among adults with normal BMI, the PRs were 1.337 (1.224–1.461), 1.323 (1.193–1.456) and 1.261 (1.152–1.381) separately when adjusted for gender, age and BMI. Conclusions Hypertension, diabetes and hyperlipidemia were significantly associated with central obesity among adults with normal BMI in Jilin Province, China. The low rates of awareness and control of central obesity among adults with normal BMI should be improved by government and health department. PMID:27467819

  9. Maternal age affects brain metabolism in adult children of mothers affected by Alzheimer’s disease

    PubMed Central

    Mosconi, Lisa; Tsui, Wai; Murray, John; McHugh, Pauline; Li, Yi; Williams, Schantel; Pirraglia, Elizabeth; Glodzik, Lidia; De Santi, Susan; Vallabhajosula, Shankar; de Leon, Mony J.

    2011-01-01

    Cognitively normal (NL) individuals with a maternal history of late-onset Alzheimer’s disease (MH) show reduced brain glucose metabolism on FDG-PET as compared to those with a paternal history (PH) and those with negative family history (NH) of Alzheimer’s disease (AD). This FDG-PET study investigates whether metabolic deficits in NL MH are associated with advancing maternal age at birth. Ninety-six NL individuals with FDG-PET were examined, including 36 MH, 24 PH, and 36 NH. Regional-to-whole brain gray matter standardized FDG uptake value ratios were examined for associations with parental age across groups using automated regions-of-interest and statistical parametric mapping. Groups were comparable for clinical and neuropsychological measures. Brain metabolism in AD-vulnerable regions was lower in MH compared to NH and PH, and negatively correlated with maternal age at birth only in MH. There were no associations between paternal age and metabolism in any group. Evidence for a maternally inherited, maternal age-related mechanism provides further insight on risk factors and genetic transmission in late-onset AD. PMID:21514691

  10. Maternal age affects brain metabolism in adult children of mothers affected by Alzheimer's disease.

    PubMed

    Mosconi, Lisa; Tsui, Wai; Murray, John; McHugh, Pauline; Li, Yi; Williams, Schantel; Pirraglia, Elizabeth; Glodzik, Lidia; De Santi, Susan; Vallabhajosula, Shankar; de Leon, Mony J

    2012-03-01

    Cognitively normal (NL) individuals with a maternal history of late-onset Alzheimer's disease (MH) show reduced brain glucose metabolism on FDG-PET as compared to those with a paternal history (PH) and those with negative family history (NH) of Alzheimer's disease (AD). This FDG-PET study investigates whether metabolic deficits in NL MH are associated with advancing maternal age at birth. Ninety-six NL individuals with FDG-PET were examined, including 36 MH, 24 PH, and 36 NH. Regional-to-whole brain gray matter standardized FDG uptake value ratios were examined for associations with parental age across groups using automated regions-of-interest and statistical parametric mapping. Groups were comparable for clinical and neuropsychological measures. Brain metabolism in AD-vulnerable regions was lower in MH compared to NH and PH, and negatively correlated with maternal age at birth only in MH. There were no associations between paternal age and metabolism in any group. Evidence for a maternally inherited, maternal age-related mechanism provides further insight on risk factors and genetic transmission in late-onset AD.

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

    PubMed Central

    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, including body weight, height and waist circumference were collected. Blood pressure, triglyceride, cholesterol, high density lipoprotein-cholesterol and fasting plasma glucose, renal function and 24-hour urine protein were measured. The correlations between GFR and actual nutrient intakes of participants were examined. Results: The actual intakes of energy, carbohydrates, protein, fat and cholesterol in participate were all significantly higher than recommended nutrient intakes/adequate intakes of Chinese Dietary Reference Intakes. GFR was significantly inversely correlated with energy, protein intake, cholesterol intake, carbohydrates intake, sodium intake, calcium intake and actual protein/energy ratio. Logistic regression analyses showed that actual protein intakes/recommended protein intakes (APIs/RPIs) were significant independent predictors of GFR < 60 ml/min•1.73 m2. Conclusions: Dietary nutrition is closely correlated with kidney damage in patients with metabolic syndrome. High protein intakes may be one of the risk factors of renal damage. PMID:25550967

  12. Adult Still's disease

    MedlinePlus

    Still's disease - adult; AOSD ... than 1 out of 100,000 people develop adult-onset Still's disease each year. It affects women more often than men. The cause of adult Still's disease is unknown. No risk factors for ...

  13. Resolution of metabolic syndrome after following a gluten free diet in an adult woman diagnosed with celiac disease

    PubMed Central

    García-Manzanares, Álvaro; Lucendo, Alfredo J; González-Castillo, Sonia; Moreno-Fernández, Jesús

    2011-01-01

    Adult celiac disease (CD) presents with very diverse symptoms that are clearly different from those typically seen in pediatric patients, including ferropenic anemia, dyspepsia, endocrine alterations and elevated transaminase concentration. We present the case of a 51-year-old overweight woman with altered basal blood glucose, hypercholesterolemia, hypertriglyceridemia and persisting elevated transaminase levels, who showed all the symptoms for a diagnosis of metabolic syndrome. Because she presented iron deficiency anemia, she was referred to the gastroenterology department and subsequently diagnosed with celiac disease after duodenal biopsies and detection of a compatible HLA haplotype. Gluten-free diet (GFD) was prescribed and after 6 mo the patient showed resolution of laboratory abnormalities (including recovering anemia and iron reserves, normalization of altered lipid and liver function parameters and decrease of glucose blood levels). No changes in weight or waist circumference were observed and no significant changes in diet were documented apart from the GFD. The present case study is the first reported description of an association between CD and metabolic syndrome, and invites investigation of the metabolic changes induced by gluten in celiac patients. PMID:21860836

  14. Aberrant Lipid Metabolism in the Forebrain Niche Suppresses Adult Neural Stem Cell Proliferation in an Animal Model of Alzheimer's Disease.

    PubMed

    Hamilton, Laura K; Dufresne, Martin; Joppé, Sandra E; Petryszyn, Sarah; Aumont, Anne; Calon, Frédéric; Barnabé-Heider, Fanie; Furtos, Alexandra; Parent, Martin; Chaurand, Pierre; Fernandes, Karl J L

    2015-10-01

    Lipid metabolism is fundamental for brain development and function, but its roles in normal and pathological neural stem cell (NSC) regulation remain largely unexplored. Here, we uncover a fatty acid-mediated mechanism suppressing endogenous NSC activity in Alzheimer's disease (AD). We found that postmortem AD brains and triple-transgenic Alzheimer's disease (3xTg-AD) mice accumulate neutral lipids within ependymal cells, the main support cell of the forebrain NSC niche. Mass spectrometry and microarray analyses identified these lipids as oleic acid-enriched triglycerides that originate from niche-derived rather than peripheral lipid metabolism defects. In wild-type mice, locally increasing oleic acid was sufficient to recapitulate the AD-associated ependymal triglyceride phenotype and inhibit NSC proliferation. Moreover, inhibiting the rate-limiting enzyme of oleic acid synthesis rescued proliferative defects in both adult neurogenic niches of 3xTg-AD mice. These studies support a pathogenic mechanism whereby AD-induced perturbation of niche fatty acid metabolism suppresses the homeostatic and regenerative functions of NSCs.

  15. Liver repopulation and correction of metabolic liver disease by transplanted adult mouse pancreatic cells.

    PubMed

    Wang, X; Al-Dhalimy, M; Lagasse, E; Finegold, M; Grompe, M

    2001-02-01

    The emergence of cells with hepatocellular properties in the adult pancreas has been described in several experimental models. To determine whether adult pancreas contains cells that can give rise to therapeutically useful and biochemically normal hepatocytes, we transplanted suspensions of wild-type mouse pancreatic cells into syngeneic recipients deficient in fumarylacetoacetate hydrolase and manifesting tyrosinemia. Four of 34 (12%) mutant mice analyzed were fully rescued by donor-derived cells and had normal liver function. Ten additional mice (29%) showed histological evidence of donor-derived hepatocytes in the liver. Previous work has suggested that pancreatic liver precursors reside within or close to pancreatic ducts. We therefore performed additional transplantations using either primary cell suspensions enriched for ducts or cultured ducts. Forty-four mutant mice were transplanted with cells enriched for pancreatic duct cells, but only three of the 34 (9%) recipients analyzed displayed donor-derived hepatocytes. In addition, 28 of the fumarylacetoacetate hydrolase-deficient mice were transplanted with cultured pancreatic duct cells, but no donor-derived hepatocytes were observed. Our results demonstrate for the first time that adult mouse pancreas contains hepatocyte progenitor cells capable of significant therapeutic liver reconstitution. However, contrary to previous reports, we were unable to detect these cells within the duct compartment. PMID:11159194

  16. Wilson's disease in an adult asymptomatic patient: a potential role for modifying factors of copper metabolism.

    PubMed

    Loudianos, Georgios; Incollu, Simona; Mameli, Eva; Lepori, Maria B

    2016-01-01

    Diagnosis of Wilson's disease (WD) still remains a challenge since no single test has an accuracy of 100%. Molecular testing for ATP7B gene mutations can help reach the diagnosis when routine testing is equivocal. We herein report an asymptomatic WD patient diagnosed accidentally by genetic analysis. Th is case suggests that WD is a challenge even in particular contexts such as family screening. Genetic testing of ATP7B gene should be recommended in the family members of WD patients with minimal alterations of specific tests such as ceruloplasmin, and presence of steatosis or increased body mass index.

  17. Wilson's disease in an adult asymptomatic patient: a potential role for modifying factors of copper metabolism.

    PubMed

    Loudianos, Georgios; Incollu, Simona; Mameli, Eva; Lepori, Maria B

    2016-01-01

    Diagnosis of Wilson's disease (WD) still remains a challenge since no single test has an accuracy of 100%. Molecular testing for ATP7B gene mutations can help reach the diagnosis when routine testing is equivocal. We herein report an asymptomatic WD patient diagnosed accidentally by genetic analysis. Th is case suggests that WD is a challenge even in particular contexts such as family screening. Genetic testing of ATP7B gene should be recommended in the family members of WD patients with minimal alterations of specific tests such as ceruloplasmin, and presence of steatosis or increased body mass index. PMID:26752957

  18. Bone Mass and Mineral Metabolism Alterations in Adult Celiac Disease: Pathophysiology and Clinical Approach

    PubMed Central

    Di Stefano, Michele; Mengoli, Caterina; Bergonzi, Manuela; Corazza, Gino Roberto

    2013-01-01

    Osteoporosis affects many patients with celiac disease (CD), representing the consequence of calcium malabsorption and persistent activation of mucosal inflammation. A slight increase of fracture risk is evident in this condition, particularly in those with overt malabsorption and in postmenopausal state. The adoption of a correct gluten-free diet (GFD) improves bone derangement, but is not able to normalize bone mass in all the patients. Biomarkers effective in the prediction of bone response to gluten-free diet are not yet available and the indications of guidelines are still imperfect and debated. In this review, the pathophysiology of bone loss is correlated to clinical aspects, defining an alternative proposal of management for this condition. PMID:24284619

  19. Chronic obstructive pulmonary disease - adults - discharge

    MedlinePlus

    ... adults - discharge; Chronic obstructive airways disease - adults - discharge; Chronic obstructive lung disease - adults - discharge; Chronic bronchitis - adults - discharge; Emphysema - adults - ...

  20. [Rare metabolic diseases].

    PubMed

    Wendel, U; Burgard, P

    2007-12-01

    Rare metabolic diseases are chronic, progressive, present frequently with a life-threatening course and may result in severe handicaps. They demand high diagnostic and therapeutic standards and efforts from physicians and patients. The challenge for society and health systems in dealing with patients affected by one of these diseases is to offer comprehensive service by a multi-professional team of specialists and evidence-based as well as economic (i.e. necessary, sufficient and effective) treatment. Patients and families should be treated in specialized metabolic centres guaranteeing continuous improvement of the scientific and clinical principles of treatment, standardized outcome evaluation, strict quality assurance as well as optimal psychosocial care and counselling. Networking of national and international metabolic centres seems imperative for clinical research in the field of rare metabolic diseases in order to provide adequate sample sizes and to yield substantial results.

  1. Intrauterine metabolic programming alteration increased susceptibility to non-alcoholic adult fatty liver disease in prenatal caffeine-exposed rat offspring.

    PubMed

    Wang, Linlong; Shen, Lang; Ping, Jie; Zhang, Li; Liu, Zhongfen; Wu, Yong; Liu, Yansong; Huang, Hegui; Chen, Liaobin; Wang, Hui

    2014-01-30

    An increase in susceptibility to metabolic syndromes (MetS) in rat offspring that experienced prenatal caffeine exposure (PCE) has been previously demonstrated. The present study aimed to clarify this increased susceptibility and elucidate the mechanism of foetal origin that causes or contributes to adult non-alcoholic fatty liver disease (NAFLD) as a result of PCE. Based on the results from both foetal and adult studies of rats that experienced PCE (120 mg/kgd), the foetal weight and serum triglyceride levels decreased significantly and hepatocellular ultrastructure was altered. Foetal livers exhibited inhibited insulin-like growth factor-1 (IGF-1), enhanced lipogenesis and reduced lipid output. In adult female offspring of PCE+lab chow, lipid synthesis, oxidation and output were enhanced, whereas lipogenesis was inhibited in their male conterparters. Furthermore, in adult offspring of PCE+ high-fat diet, catch-up growth appeared obvious with enhanced hepatic IGF-1, especially in females. Both males and females showed increased lipid synthesis and reduced output, which were accompanied by elevated serum triglyceride. Severe NAFLD appeared with higher Kleiner scores. Gluconeogenesis was continuously enhanced in females. Therefore, increased susceptibility to diet-induced NAFLD in PCE offspring was confirmed, and it appears to be mediated by intrauterine glucose and alterations in lipid metabolic programming. This altered programming enhanced foetal hepatic lipogenesis and reduced lipid output in utero, which continued into the postnatal phase and reappeared in adulthood with the introduction of a high-fat diet, thereby aggravating hepatic lipid accumulation and causing NAFLD.

  2. Metabolic Syndrome: An Important Risk Factor for Parkinson's Disease

    PubMed Central

    Tian, Bo

    2014-01-01

    Metabolic syndrome is becoming commoner due to a rise in obesity rates among adults. Generally speaking, a person with metabolic syndrome is twice as likely to develop cardiovascular disease and five times as likely to develop diabetes as someone without metabolic syndrome. Increasing oxidative stress in metabolic syndrome and Parkinson's disease is mentioned in the comprehensive articles; however, the system review about clear relation between metabolic syndrome and Parkinson's disease is deficient. In this review, we will focus on the analysis that the metabolic syndrome may be a risk factor for Parkinson's disease and the preventions that reduce the incident of Parkinson's disease by regulating the oxidative stress. PMID:24955210

  3. The programming effects of nutrition-induced catch-up growth on gut microbiota and metabolic diseases in adult mice.

    PubMed

    Zheng, Jia; Xiao, Xinhua; Zhang, Qian; Yu, Miao; Xu, Jianping; Qi, Cuijuan; Wang, Tong

    2016-04-01

    Substantial evidence indicated that catch-up growth could increase the susceptibility to obesity, insulin resistance, and type 2 diabetes mellitus in adulthood. However, investigations into the "programming" effects of catch-up growth on gut microbiota in the offspring are limited. C57/BL6 mice were fed on either low protein (LP) or normal chow (NC) diet throughout gestation and lactation. Then, the offspring were randomly weaned to either NC or high fat (HF) diet until 32 weeks of age, generating four experimental groups: NC-NC, NC-HF, LP-NC, and LP-HF. Metabolic parameters and gut microbiota were examined in the offspring. It showed that the NC-HF and LP-HF offspring displayed higher body weight (P < 0.05), impaired glucose tolerance (P < 0.001), and elevated serum lipids (P < 0.05) at 32 weeks of age. Both the operational taxonomic units (OTUs) and the Shannon indexes (P < 0.05) showed significantly lower microbial diversity in NC-HF and LP-HF offspring. There were significant variations in the compositions of gut microbiota in the NC-HF and LP-HF offspring, compared with NC-NC offspring (P < 0.05). Furthermore, it indicated Lactobacillus percentage was negatively associated with blood glucose concentrations of intraperitoneal glucose tolerance test (r = -0.886, P = 0.019). In conclusion, catch-up growth predisposes the offspring to gut microbiota perturbation, obesity, impaired glucose tolerance, insulin resistance, and dyslipidemia. Our study is novel in showing the "programming" effects of nutrition-induced catch-up growth on gut microbiota and metabolic diseases in later life. PMID:26749443

  4. The programming effects of nutrition-induced catch-up growth on gut microbiota and metabolic diseases in adult mice.

    PubMed

    Zheng, Jia; Xiao, Xinhua; Zhang, Qian; Yu, Miao; Xu, Jianping; Qi, Cuijuan; Wang, Tong

    2016-04-01

    Substantial evidence indicated that catch-up growth could increase the susceptibility to obesity, insulin resistance, and type 2 diabetes mellitus in adulthood. However, investigations into the "programming" effects of catch-up growth on gut microbiota in the offspring are limited. C57/BL6 mice were fed on either low protein (LP) or normal chow (NC) diet throughout gestation and lactation. Then, the offspring were randomly weaned to either NC or high fat (HF) diet until 32 weeks of age, generating four experimental groups: NC-NC, NC-HF, LP-NC, and LP-HF. Metabolic parameters and gut microbiota were examined in the offspring. It showed that the NC-HF and LP-HF offspring displayed higher body weight (P < 0.05), impaired glucose tolerance (P < 0.001), and elevated serum lipids (P < 0.05) at 32 weeks of age. Both the operational taxonomic units (OTUs) and the Shannon indexes (P < 0.05) showed significantly lower microbial diversity in NC-HF and LP-HF offspring. There were significant variations in the compositions of gut microbiota in the NC-HF and LP-HF offspring, compared with NC-NC offspring (P < 0.05). Furthermore, it indicated Lactobacillus percentage was negatively associated with blood glucose concentrations of intraperitoneal glucose tolerance test (r = -0.886, P = 0.019). In conclusion, catch-up growth predisposes the offspring to gut microbiota perturbation, obesity, impaired glucose tolerance, insulin resistance, and dyslipidemia. Our study is novel in showing the "programming" effects of nutrition-induced catch-up growth on gut microbiota and metabolic diseases in later life.

  5. Developmental origins of adult diseases

    PubMed Central

    Mathew, Vivek; Ayyar, S. Vageesh

    2012-01-01

    There is considerable evidence for the fact that early life environment in human beings are associated with future development of various metabolic diseases. Fetal programming and perinatal events appear to exert effects on later life that are independent of environmental risk factors in adults. Our understanding of the underlying mechanisms are limited and remains unclear. However several animal models and epidemiological studies have shown this association, and it is assumed secondary to the penalties of developmental plasticity. In this review, we amalgamate facts from several disciplines to support this hypothesis. PMID:22837912

  6. Metabolic disease in animals.

    PubMed

    Liu, Si-Kwang

    2002-12-01

    Rickets is a metabolic bone disorder characterized by osteopenic changes resulting from the failure of calcification of the osteoid matrix and absent mineralization of hypertrophic cartilage cells at the epiphyseal growth plates in growing primates, herbivores, swine, carnivores, and birds. The causes of rickets include inadequate dietary provision of calcium, phosphorus, and vitamin D. Osteomalacia in reptiles, simian bone disease in nonhuman primates, and osteodystrophia fibrosa (secondary hyperparathyroidism) or "bran disease" in herbivores are caused by a diet that has a much higher content of phosphorus than calcium, combined with inadequate exposure to direct sunlight. Medullary bone consists of interconnected spicules of bone resembling embryonic bone and is established in relation to the shell formation cycle of laying birds. Hypertrophic osteodystrophy develops in large-breed growing dogs, chickens, and guinea pigs and is possibly caused by vitamin C deficiency. Tibial dyschondroplasia is a defect in endochondral ossification characterized by a widened proximal tibial physis that is not penetrated by metaphyseal vascular sprouts, commonly found in growing broiler chickens, turkeys, and exotic birds. PMID:12541191

  7. Metabolism of phytanic acid and 3-methyl-adipic acid excretion in patients with adult Refsum disease.

    PubMed

    Wierzbicki, Anthony S; Mayne, Phillip D; Lloyd, Matthew D; Burston, David; Mei, Guam; Sidey, Margaret C; Feher, Michael D; Gibberd, F Brian

    2003-08-01

    Adult Refsum disease (ARD) is associated with defective alpha-oxidation of phytanic acid (PA). omega-Oxidation of PA to 3-methyl-adipic acid (3-MAA) occurs although its clinical significance is unclear. In a 40 day study of a new ARD patient, where the plasma half-life of PA was 22.4 days, omega-oxidation accounted for 30% initially and later all PA excretion. Plasma and adipose tissue PA and 3-MAA excretion were measured in a cross-sectional study of 11 patients. The capacity of the omega-oxidation pathway was 6.9 (2.8-19.4) mg [20.4 (8.3-57.4) micromol] PA/day. 3-MAA excretion correlated with plasma PA levels (r = 0.61; P = 0.03) but not adipose tissue PA content. omega-Oxidation during a 56 h fast was studied in five patients. 3-MAA excretion increased by 208 +/- 58% in parallel with the 158 (125-603)% rise in plasma PA. Plasma PA doubled every 29 h, while 3-MAA excretion followed second-order kinetics. Acute sequelae of ARD were noted in three patients (60%) after fasting. The omega-oxidation pathway can metabolise PA ingested by patients with ARD, but this activity is dependent on plasma PA concentration. omega-Oxidation forms a functional reserve capacity that enables patients with ARD undergoing acute stress to cope with limited increases in plasma PA levels.

  8. Renal Disease and Adult Vaccination

    MedlinePlus

    ... Resources for Healthcare Professionals Renal Disease and Adult Vaccination Recommend on Facebook Tweet Share Compartir Vaccines are ... have immunity to this disease Learn about adult vaccination and other health conditions Asplenia Diabetes Type 1 ...

  9. Liver Disease and Adult Vaccination

    MedlinePlus

    ... Resources for Healthcare Professionals Liver Disease and Adult Vaccination Recommend on Facebook Tweet Share Compartir Vaccines are ... have immunity to this disease Learn about adult vaccination and other health conditions Asplenia Diabetes Type 1 ...

  10. Diagnosis of metabolic bone disease

    SciTech Connect

    Grech, P.; Martin, T.J.; Barrington, N.A.; Ell, P.J.

    1986-01-01

    This book presents a reference on the radiologic evaluation, features, and differential diagnosis of metabolic diseases involving the whole skeleton, calcium deficiencies resulting from pharmacologic agents, and bone changes related to endocrine disturbances. It also stresses how radiology, nuclear medicine, and biochemistry - either alone or in concert - contribute to clinical diagnosis. It covers renal bone disease, Paget's disease, hyperphosphatasia, extraskeletal mineralization, metabolic bone disorders related to malnutrition, tumors, plus radionuclide studies including materials and methods.

  11. Metabolic syndrome and eye diseases.

    PubMed

    Poh, Stanley; Mohamed Abdul, Riswana Banu Binte; Lamoureux, Ecosse L; Wong, Tien Y; Sabanayagam, Charumathi

    2016-03-01

    Metabolic syndrome is becoming a worldwide medical and public health challenge as it has been seen increasing in prevalence over the years. Age-related eye diseases, the leading cause of blindness globally and visual impairment in developed countries, are also on the rise due to aging of the population. Many of the individual components of the metabolic syndrome have been shown to be associated with these eye diseases. However, the association of metabolic syndrome with eye diseases is not clear. In this review, we reviewed the evidence for associations between metabolic syndrome and certain ocular diseases in populations. We also reviewed the association of individual metabolic syndrome components with ocular diseases due to a paucity of research in this area. Besides, we also summarised the current understanding of etiological mechanisms of how metabolic syndrome or the individual components lead to these ocular diseases. With increasing evidence of such associations, it may be important to identify patients who are at risk of developing metabolic syndrome as prompt treatment and intervention may potentially decrease the risk of developing certain ocular diseases.

  12. Metabolic disease in HIV infection.

    PubMed

    Lake, Jordan E; Currier, Judith S

    2013-11-01

    The treatment of metabolic disease is becoming an increasingly important component of the long-term management of patients with well controlled HIV on antiretroviral therapy (ART). Metabolic diseases probably develop at the intersection of traditional risk factors (such as obesity, tobacco use, and genetic predisposition) and HIV-specific and ART-specific contributors (including chronic inflammation and immune activation). This Review discusses present knowledge on adipose tissue dysfunction, insulin-glucose homoeostasis, lipid disturbances, and cardiovascular disease risk in people with HIV on ART. Although new antiretroviral drugs are believed to induce fewer short-term metabolic perturbations than do older drugs, the long-term effects of these drugs are not fully understood. Additionally, patients remain at increased risk of cardiovascular disease and other metabolic comorbidities. Research and treatment should focus on selection of ART that is both virologically effective and has minimum metabolic effects, minimisation of traditional risk factors for metabolic disease, and development of novel therapies to treat metabolic disease in patients with HIV, including use of anti-inflammatory and immunomodulatory drugs.

  13. Lysophosphatidylinositol Signalling and Metabolic Diseases.

    PubMed

    Arifin, Syamsul A; Falasca, Marco

    2016-01-01

    Metabolism is a chemical process used by cells to transform food-derived nutrients, such as proteins, carbohydrates and fats, into chemical and thermal energy. Whenever an alteration of this process occurs, the chemical balance within the cells is impaired and this can affect their growth and response to the environment, leading to the development of a metabolic disease. Metabolic syndrome, a cluster of several metabolic risk factors such as abdominal obesity, insulin resistance, high cholesterol and high blood pressure, and atherogenic dyslipidaemia, is increasingly common in modern society. Metabolic syndrome, as well as other diseases, such as diabetes, obesity, hyperlipidaemia and hypertension, are associated with abnormal lipid metabolism. Cellular lipids are the major component of cell membranes; they represent also a valuable source of energy and therefore play a crucial role for both cellular and physiological energy homeostasis. In this review, we will focus on the physiological and pathophysiological roles of the lysophospholipid mediator lysophosphatidylinositol (LPI) and its receptor G-protein coupled receptor 55 (GPR55) in metabolic diseases. LPI is a bioactive lipid generated by phospholipase A (PLA) family of lipases which is believed to play an important role in several diseases. Indeed LPI can affect various functions such as cell growth, differentiation and motility in a number of cell-types. Recently published data suggest that LPI plays an important role in different physiological and pathological contexts, including a role in metabolism and glucose homeostasis. PMID:26784247

  14. Lysophosphatidylinositol Signalling and Metabolic Diseases

    PubMed Central

    Arifin, Syamsul A.; Falasca, Marco

    2016-01-01

    Metabolism is a chemical process used by cells to transform food-derived nutrients, such as proteins, carbohydrates and fats, into chemical and thermal energy. Whenever an alteration of this process occurs, the chemical balance within the cells is impaired and this can affect their growth and response to the environment, leading to the development of a metabolic disease. Metabolic syndrome, a cluster of several metabolic risk factors such as abdominal obesity, insulin resistance, high cholesterol and high blood pressure, and atherogenic dyslipidaemia, is increasingly common in modern society. Metabolic syndrome, as well as other diseases, such as diabetes, obesity, hyperlipidaemia and hypertension, are associated with abnormal lipid metabolism. Cellular lipids are the major component of cell membranes; they represent also a valuable source of energy and therefore play a crucial role for both cellular and physiological energy homeostasis. In this review, we will focus on the physiological and pathophysiological roles of the lysophospholipid mediator lysophosphatidylinositol (LPI) and its receptor G-protein coupled receptor 55 (GPR55) in metabolic diseases. LPI is a bioactive lipid generated by phospholipase A (PLA) family of lipases which is believed to play an important role in several diseases. Indeed LPI can affect various functions such as cell growth, differentiation and motility in a number of cell-types. Recently published data suggest that LPI plays an important role in different physiological and pathological contexts, including a role in metabolism and glucose homeostasis. PMID:26784247

  15. Metabolic syndrome and dietary components are associated with coronary artery disease risk score in free-living adults: a cross-sectional study

    PubMed Central

    2011-01-01

    Background Coronary artery disease (CAD) is among the main causes of death in developed countries, and diet and lifestyle can influence CAD incidence. Objective To evaluate the association of coronary artery disease risk score with dietary, anthropometric and biochemical components in adults clinically selected for a lifestyle modification program. Methods 362 adults (96 men, 266 women, 53.9 ± 9.4 years) fulfilled the inclusion criteria by presenting all the required data. The Framingham score was calculated and the IV Brazilian Guideline on Dyslipidemia and Prevention of Atherosclerosis was adopted for classification of the CAD risks. Anthropometric assessments included waist circumference (WC), body fat and calculated BMI (kg/m2) and muscle-mass index (MMI kg/m2). Dietary intake was estimated through 24 h dietary recall. Fasting blood was used for biochemical analysis. Metabolic Syndrome (MS) was diagnosed using NCEP-ATPIII (2001) criteria. Logistic regression was used to determine the odds of CAD risks according to the altered components of MS, dietary, anthropometric, and biochemical components. Results For a sample with a BMI 28.5 ± 5.0 kg/m2 the association with lower risk (<10% CAD) were lower age (<60 years old), and plasma values of uric acid. The presence of MS within low, intermediary, and high CAD risk categories was 30.8%, 55.5%, and 69.8%, respectively. The independent risk factors associated with CAD risk score was MS and uric acid, and the protective factors were recommended intake of saturated fat and fiber and muscle mass index. Conclusion Recommended intake of saturated fat and dietary fiber, together with proper muscle mass, are inversely associated with CAD risk score. On the other hand, the presence of MS and high plasma uric acid are associated with CAD risk score. PMID:21554698

  16. Is Cancer a Metabolic Disease?

    PubMed Central

    Coller, Hilary A.

    2015-01-01

    Although cancer has historically been viewed as a disorder of proliferation, recent evidence has suggested that it should also be considered a metabolic disease. Growing tumors rewire their metabolic programs to meet and even exceed the bioenergetic and biosynthetic demands of continuous cell growth. The metabolic profile observed in cancer cells often includes increased consumption of glucose and glutamine, increased glycolysis, changes in the use of metabolic enzyme isoforms, and increased secretion of lactate. Oncogenes and tumor suppressors have been discovered to have roles in cancer-associated changes in metabolism as well. The metabolic profile of tumor cells has been suggested to reflect the rapid proliferative rate. Cancer-associated metabolic changes may also reveal the importance of protection against reactive oxygen species or a role for secreted lactate in the tumor microenvironment. This article reviews recent research in the field of cancer metabolism, raising the following questions: Why do cancer cells shift their metabolism in this way? Are the changes in metabolism in cancer cells a consequence of the changes in proliferation or a driver of cancer progression? Can cancer metabolism be targeted to benefit patients? PMID:24139946

  17. Transgenerational inheritance of metabolic disease.

    PubMed

    Stegemann, Rachel; Buchner, David A

    2015-07-01

    Metabolic disease encompasses several disorders including obesity, type 2 diabetes, and dyslipidemia. Recently, the incidence of metabolic disease has drastically increased, driven primarily by a worldwide obesity epidemic. Transgenerational inheritance remains controversial, but has been proposed to contribute to human metabolic disease risk based on a growing number of proof-of-principle studies in model organisms ranging from Caenorhabditis elegans to Mus musculus to Sus scrofa. Collectively, these studies demonstrate that heritable risk is epigenetically transmitted from parent to offspring over multiple generations in the absence of a continued exposure to the triggering stimuli. A diverse assortment of initial triggers can induce transgenerational inheritance including high-fat or high-sugar diets, low-protein diets, various toxins, and ancestral genetic variants. Although the mechanistic basis underlying the transgenerational inheritance of disease risk remains largely unknown, putative molecules mediating transmission include small RNAs, histone modifications, and DNA methylation. Due to the considerable impact of metabolic disease on human health, it is critical to better understand the role of transgenerational inheritance of metabolic disease risk to open new avenues for therapeutic intervention and improve upon the current methods for clinical diagnoses and treatment.

  18. Transgenerational Inheritance of Metabolic Disease

    PubMed Central

    Stegemann, Rachel; Buchner, David A.

    2015-01-01

    Metabolic disease encompasses several disorders including obesity, type 2 diabetes, and dyslipidemia. Recently, the incidence of metabolic disease has drastically increased, driven primarily by a worldwide obesity epidemic. Transgenerational inheritance remains controversial, but has been proposed to contribute to human metabolic disease risk based on a growing number of proof-of-principle studies in model organisms ranging from C. elegans to M. musculus to S. scrofa. Collectively, these studies demonstrate that heritable risk is epigenetically transmitted from parent to offspring over multiple generations in the absence of a continued exposure to the triggering stimuli. A diverse assortment of initial triggers can induce transgenerational inheritance including high-fat or high-sugar diets, low-protein diets, various toxins, and ancestral genetic variants. Although the mechanistic basis underlying the transgenerational inheritance of disease risk remains largely unknown, putative molecules mediating transmission include small RNAs, histone modifications, and DNA methylation. Due to the considerable impact of metabolic disease on human health, it is critical to better understand the role of transgenerational inheritance of metabolic disease risk to open new avenues for therapeutic intervention and improve upon the current methods for clinical diagnoses and treatment. PMID:25937492

  19. Cellular metabolism and disease: what do metabolic outliers teach us?

    PubMed Central

    DeBerardinis, Ralph J.; Thompson, Craig B.

    2012-01-01

    An understanding of metabolic pathways based solely on biochemistry textbooks would underestimate the pervasive role of metabolism in essentially every aspect of biology. It is evident from recent work that many human diseases involve abnormal metabolic states – often genetically programmed – that perturb normal physiology and lead to severe tissue dysfunction. Understanding these metabolic outliers is now a crucial frontier in disease-oriented research. This review discusses the broad impact of metabolism in cellular function, how modern concepts of metabolism can inform our understanding of common diseases like cancer, and considers the prospects of developing new metabolic approaches to disease treatment. PMID:22424225

  20. Cancer as a metabolic disease

    PubMed Central

    2010-01-01

    Emerging evidence indicates that impaired cellular energy metabolism is the defining characteristic of nearly all cancers regardless of cellular or tissue origin. In contrast to normal cells, which derive most of their usable energy from oxidative phosphorylation, most cancer cells become heavily dependent on substrate level phosphorylation to meet energy demands. Evidence is reviewed supporting a general hypothesis that genomic instability and essentially all hallmarks of cancer, including aerobic glycolysis (Warburg effect), can be linked to impaired mitochondrial function and energy metabolism. A view of cancer as primarily a metabolic disease will impact approaches to cancer management and prevention. PMID:20181022

  1. Lower fibroblast growth factor 23 levels in young adults with Crohn disease as a possible secondary compensatory effect on the disturbance of bone and mineral metabolism.

    PubMed

    Oikonomou, Konstantinos A; Orfanidou, Timoklia I; Vlychou, Marianna K; Kapsoritakis, Andreas N; Tsezou, Aspasia; Malizos, Konstantinos N; Potamianos, Spyros P

    2014-01-01

    Fibroblast growth factor 23 (FGF-23) is a bone-derived circulating phosphaturic factor that decreases serum concentration of phosphate and vitamin D, suggested to actively participate in a complex renal-gastrointestinal-skeletal axis. Serum FGF-23 concentrations, as well as various other laboratory parameters involved in bone homeostasis, were measured and analyzed with regard to various diseases and patients' characteristics in 44 patients with Crohn disease (CD) and 20 healthy controls (HCs) included in this cross-sectional study. Serum FGF-23 levels were significantly lower in patients with CD (900.42 ± 815.85pg/mL) compared with HC (1410.94 ± 1000.53pg/mL), p = 0.037. Further analyses suggested FGF-23 as a factor independent from various parameters including age (r = -0.218), body mass index (r = -0.115), 25-hydroxy vitamin D (r = 0.126), parathyroid hormone (r = 0.084), and bone mineral density (BMD) of hip and lumbar (r = 0.205 and r = 0.149, respectively). This observation remained even after multivariate analyses, exhibiting that BMD was not affected by FGF-23, although parameters such as age (p = 0.026), cumulative prednisolone dose (p < 0.0001), and smoking status (p = 0.024) were strong determinants of BMD regarding hip. Lower FGF-23 levels in patients with bowel inflammation are accompanied but not directly correlated with lower vitamin D levels, showing no impact on BMD determination of young adults with CD. The downregulation of serum FGF-23 levels in CD appears as a secondary compensatory effect on the bone and mineral metabolism induced by chronic intestinal inflammation.

  2. Early-Life Exposure to Antibiotics, Alterations in the Intestinal Microbiome, and Risk of Metabolic Disease in Children and Adults.

    PubMed

    Yallapragada, Sushmita G; Nash, Colleen B; Robinson, Daniel T

    2015-11-01

    The intestinal microbiome is a complex ecosystem of microorganisms that colonize the human gastrointestinal tract. The microbiome evolves rapidly in early life with contributions from diet, genetics and immunomodulatory factors. Changes in composition of the microbiota due to antibiotics may lead to negative long-term effects including obesity and diabetes mellitus, as evidenced by both animal and large human studies. Inappropriate exposures to antibiotics occur frequently in early childhood. Therefore, an evidence-based system of antimicrobial use should be employed by all providers, especially those who care for pediatric patients. This article explores the natural evolution of the intestinal microbiome from the perinatal period into early childhood, the effect of antibiotics on the microbial ecology, and the implications for future health and disease.

  3. [Inborn errors of metabolism in adult neurology].

    PubMed

    Sedel, F

    2013-02-01

    Inborn errors of metabolism (IEM) are caused by mutations in genes coding for enzymes and other proteins involved in cell metabolism. Many IEM can be treated effectively. Although IEM have usually been considered pediatric diseases, they can present at any age, mostly with neurological and psychiatric symptoms, and therefore constitute an integral subspeciality of neurology. However, although they are increasingly being recognized, IEM remain rare, and the care for patients should be optimized in specialized reference centers. Since the number of different diseases is very large, the diagnostic approach needs to be rigorous, starting at the clinics and calling upon the additional help of neuroradiology, biochemistry and molecular biology. In practice, it is important for the neurologist to recognize: (1) when to start suspecting an IEM; and (2) how to correlate a given clinical presentation with one of the five major groups of diseases affecting the nervous system. These five groups may be classified as: (a) energy metabolism disorders such as respiratory chain disorders, pyruvate dehydrogenase deficiency, GLUT1 deficiency, fatty-acid β-oxidation defects, and disorders involving key cofactors such as electron transfer flavoprotein, thiamine, biotin, riboflavin, vitamin E and coenzyme Q10; (b) intoxication syndromes such as porphyrias, urea-cycle defects, homocystinurias, organic acidurias and amino acidopathies; (c) lipid-storage disorders such as lysosomal storage disorders (Krabbe disease, metachromatic leukodystrophy, Niemann - Pick disease type C, Fabry disease and Gaucher's disease), peroxisomal disorders (adrenomyeloneuropathy, Refsum disease, disorders of pristanic acid metabolism, peroxisome biogenesis disorders), Tangier disease and cerebrotendinous xanthomatosis; (d) metal-storage diseases such as iron, copper and manganese metabolic disorders; and (e) neurotransmitter metabolism defects, including defects of serotonin, dopamine and glycine metabolism

  4. Is osteoarthritis a metabolic disease?

    PubMed

    Sellam, Jérémie; Berenbaum, Francis

    2013-12-01

    Obesity, together with aging and injury, is among the main risk factors for osteoarthritis. Obesity-related osteoarthritis can affect not only the weight-bearing joints, but also the hands, suggesting a role for circulating mediators released by the adipose tissue and known as adipokines. Thus, osteoarthritis may have a systemic metabolic component. Evidence from both epidemiological and biological studies support the concept of metabolic osteoarthritis, defined as a broad clinical phenotype that includes obesity-related osteoarthritis. Thus, osteoarthritis can be related to metabolic syndrome or to an accumulation of metabolic abnormalities. In addition, studies have demonstrated associations linking osteoarthritis to several components of the metabolic syndrome, such as hypertension and type 2 diabetes, independently from obesity or any of the other known risk factors for osteoarthritis. Both in vitro and in vitro findings indicate a deleterious effect of lipid and glucose abnormalities on cartilage homeostasis. Chronic low-grade inflammation is a feature shared by osteoarthritis and metabolic disorders and may contribute to the genesis of both. Thus, osteoarthritis is emerging as a disease that has a variety of phenotypes including a metabolic phenotype, in addition to the age-related and injury-related phenotypes.

  5. Iron Metabolism in Hodgkin's Disease

    PubMed Central

    Beamish, M. R.; Jones, P. Ashley; Trevett, D.; Evans, I. Howell; Jacobs, A.

    1972-01-01

    An evaluation of iron metabolism has been carried out in 23 untreated patients with Hodgkin's disease and 6 patients with other lymphomata. The reduction in red cell life span is related to the stage of the disease. There is an almost universal impairment of iron release from the reticuloendothelial system with a consequent sideropenia and failure of iron delivery to the bone marrow for erythropoiesis. This defect is found in all stages of the disease and is not related to systemic symptoms. PMID:4567182

  6. Phytoestrogen Metabolism by Adult Human Gut Microbiota.

    PubMed

    Gaya, Pilar; Medina, Margarita; Sánchez-Jiménez, Abel; Landete, José Mᵃ

    2016-08-09

    Phytoestrogens are plant-derived polyphenols with a structure similar to human estrogens. The three main groups of phytoestrogens, isoflavones, ellagitannins, and lignans, are transformed into equol, urolithins, and enterolignans, respectively, by bacteria. These metabolites have more estrogenic/antiestrogenic and antioxidant activities than their precursors, and they are more bioavailable. The aim of this study was to analyze the metabolism of isoflavones, lignans and ellagitannins by gut microbiota, and to study the possible correlation in the metabolism of these three groups of phytoestrogens. In vitro fermentation experiments were performed with feces samples from 14 healthy adult volunteers, and metabolite formation was measured by HPLC-PAD and HPLC-ESI/MS. Only the microbiota of one subject produced equol, while most of them showed production of O-desmethylangolensin (O-DMA). Significant inter-subject differences were observed in the metabolism of dihydrodaidzein and dihydrogenistein, while the glucoside isoflavones and their aglycones showed less variability, except for glycitin. Most subjects produced urolithins M-5 and E. Urolithin D was not detected, while uroltithin B was found in half of the individuals analyzed, and urolithins A and C were detected in two and four subjects, respectively. Enterolactone was found in all subjects, while enterodiol only appeared in five. Isoflavone metabolism could be correlated with the metabolism of lignans and ellagitannins. However, the metabolism of ellagitannins and lignans could not be correlated. This the first study where the metabolism of the three groups together of phytoestrogen, isoflavones, lignans, and ellagitannins by gut microbiota is analyzed.

  7. [Metabolic syndrome, a mitochondrial disease?].

    PubMed

    Gastaldi, G; Giacobino, J P; Ruiz, J

    2008-06-01

    The metabolic syndrome is a cluster of metabolic risk factors including: atherogenic dyslipidemia, elevated blood pressure, high plasma glucose and a prothrombotic and proinflammatory state, frequently associated to overweight. Impaired cell metabolism has been suggested as a relevant pathophysiological process. Indeed, the accumulation of intracellular fatty acylCoA and diacylglycerol, which then activate critical signal transduction pathways that ultimatly lead to suppression of insulin signalisation. Therefore a defect in mitochondrial function may be responsible for insulin resistance. Moreover, mitochondrial dysfunction has been found to take place in organs such as skeletal muscle, liver, pancreas and smoth vascular cells suggesting that mitochondrial defect could play a critical role in the occurence of cardiovascular diseases.

  8. Sirtuin and metabolic kidney disease.

    PubMed

    Wakino, Shu; Hasegawa, Kazuhiro; Itoh, Hiroshi

    2015-10-01

    Sirtuin is a nicotinamide adenine dinucleotide-dependent deacetylase. One of its isoforms, Sirt1, is a key molecule in glucose, lipid, and energy metabolism. The renal protective effects of Sirt1 are found in various models of renal disorders with metabolic impairment, such as diabetic nephropathy. Protective effects include the maintenance of glomerular barrier function, anti-fibrosis effects, anti-oxidative stress effects, and regulation of mitochondria function and energy metabolism. Various target molecules subject to direct deacetylation or epigenetic gene regulation have been identified as effectors of the renal protective function of sirtuin. Recently, it was demonstrated that Sirt1 expression decreases in proximal tubules before albuminuria in a mouse model of diabetic nephropathy, and that albuminuria is suppressed in proximal tubule-specific mice overexpressing Sirt1. These findings suggest that decreased Sirt1 expression in proximal tubular cells causes abnormal nicotine metabolism and reduces the supply of nicotinamide mononucleotide from renal tubules to glomeruli. This further decreases expression of Sirt1 in glomerular podocytes and increases expression of a tight junction protein, claudin-1, which results in albuminuria. Activators of the sirtuin family of proteins, including resveratrol, may be important in the development of new therapeutic strategies for treating metabolic kidney diseases, including diabetic nephropathy.

  9. Sirtuin and metabolic kidney disease

    PubMed Central

    Wakino, Shu; Hasegawa, Kazuhiro; Itoh, Hiroshi

    2015-01-01

    Sirtuin is a nicotinamide adenine dinucleotide–dependent deacetylase. One of its isoforms, Sirt1, is a key molecule in glucose, lipid, and energy metabolism. The renal protective effects of Sirt1 are found in various models of renal disorders with metabolic impairment, such as diabetic nephropathy. Protective effects include the maintenance of glomerular barrier function, anti–fibrosis effects, anti–oxidative stress effects, and regulation of mitochondria function and energy metabolism. Various target molecules subject to direct deacetylation or epigenetic gene regulation have been identified as effectors of the renal protective function of sirtuin. Recently, it was demonstrated that Sirt1 expression decreases in proximal tubules before albuminuria in a mouse model of diabetic nephropathy, and that albuminuria is suppressed in proximal tubule–specific mice overexpressing Sirt1. These findings suggest that decreased Sirt1 expression in proximal tubular cells causes abnormal nicotine metabolism and reduces the supply of nicotinamide mononucleotide from renal tubules to glomeruli. This further decreases expression of Sirt1 in glomerular podocytes and increases expression of a tight junction protein, claudin-1, which results in albuminuria. Activators of the sirtuin family of proteins, including resveratrol, may be important in the development of new therapeutic strategies for treating metabolic kidney diseases, including diabetic nephropathy. PMID:26083654

  10. Phytoestrogen Metabolism by Adult Human Gut Microbiota.

    PubMed

    Gaya, Pilar; Medina, Margarita; Sánchez-Jiménez, Abel; Landete, José Mᵃ

    2016-01-01

    Phytoestrogens are plant-derived polyphenols with a structure similar to human estrogens. The three main groups of phytoestrogens, isoflavones, ellagitannins, and lignans, are transformed into equol, urolithins, and enterolignans, respectively, by bacteria. These metabolites have more estrogenic/antiestrogenic and antioxidant activities than their precursors, and they are more bioavailable. The aim of this study was to analyze the metabolism of isoflavones, lignans and ellagitannins by gut microbiota, and to study the possible correlation in the metabolism of these three groups of phytoestrogens. In vitro fermentation experiments were performed with feces samples from 14 healthy adult volunteers, and metabolite formation was measured by HPLC-PAD and HPLC-ESI/MS. Only the microbiota of one subject produced equol, while most of them showed production of O-desmethylangolensin (O-DMA). Significant inter-subject differences were observed in the metabolism of dihydrodaidzein and dihydrogenistein, while the glucoside isoflavones and their aglycones showed less variability, except for glycitin. Most subjects produced urolithins M-5 and E. Urolithin D was not detected, while uroltithin B was found in half of the individuals analyzed, and urolithins A and C were detected in two and four subjects, respectively. Enterolactone was found in all subjects, while enterodiol only appeared in five. Isoflavone metabolism could be correlated with the metabolism of lignans and ellagitannins. However, the metabolism of ellagitannins and lignans could not be correlated. This the first study where the metabolism of the three groups together of phytoestrogen, isoflavones, lignans, and ellagitannins by gut microbiota is analyzed. PMID:27517891

  11. Niacin metabolism and Parkinson's disease.

    PubMed

    Fukushima, Tetsuhito

    2005-01-01

    Epidemiological surveys suggest an important role for niacin in the causes of Parkinson's disease, in that niacin deficiency, the nutritional condition that causes pellagra, appears to protect against Parkinson's disease. Absorbed niacin is used in the synthesis of nicotinamide adenine dinucleotide (NAD) in the body, and in the metabolic process NAD releases nicotinamide by poly(ADP-ribosyl)ation, the activation of which has been reported to mediate 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine-induced Parkinson's disease. Recently nicotinamide N-methyltransferase (EC2.1.1.1) activity has been discovered in the human brain, and the released nicotinamide may be methylated to 1-methylnicotinamide (MNA), via this enzyme, in the brain. A deficiency in mitochondrial NADH: ubiquinone oxidoreductase (complex 1) activity is believed to be a critical factor in the development of Parkinson's disease. MNA has been found to destroy several subunits of cerebral complex 1, leading to the suggestion that MNA is concerned in the pathogenesis of Parkinson's disease. Based on these findings, it is hypothesized that niacin is a causal substance in the development of Parkinson's disease through the following processes: NAD produced from niacin releases nicotinamide via poly(ADP-ribosyl)ation, activated by the hydroxyl radical. Released excess nicotinamide is methylated to MNA in the cytoplasm, and superoxides formed by MNA via complex I destroy complex 1 subunits directly, or indirectly via mitochondrial DNA damage. Hereditary or environmental factors may cause acceleration of this cycle, resulting in neuronal death.

  12. [Alimentary, metabolic and toxic osteopathies in adults].

    PubMed

    Ellegast, H H

    1986-12-01

    Skeletal changes in deficient or badly balanced nutrition (alimentary osteopathies) and osseous changes accompanying chronic disease of internal organs and metabolic disorders (metabolic osteopathies) are discussed. Basically, the classical generalised skeletal changes such as osteoporosis, osteomalacia, fibroosteoclacia and sclerosis of the bone can occur in their pure form or as a combination of two ore more of these disorders. Finally the exogenic toxic osteopathies are discussed, nowadays fluorosis being the most important. Other external factors may be drugs such as methotrexate and antiepileptic medications.

  13. Psychiatric manifestations of treatable hereditary metabolic disorders in adults

    PubMed Central

    2014-01-01

    Detecting psychiatric disorders of secondary origin is a crucial concern for the psychiatrist. But how can this reliably be done among a large number of conditions, most of which have a very low prevalence? Metabolic screening undertaken in a population of subjects with psychosis demonstrated the presence of treatable metabolic disorders in a significant number of cases. The nature of the symptoms that should alert the clinician is also a fundamental issue and is not limited to psychosis. Hereditary metabolic disorders (HMD) are a rare but important cause of psychiatric disorders in adolescents and adults, the signs of which may remain isolated for years before other more specific organic signs appear. HMDs that present purely with psychiatric symptoms are very difficult to diagnose due to low awareness of these rare diseases among psychiatrists. However, it is important to identify HMDs in order to refer patients to specialist centres for appropriate management, disease-specific treatment and possible prevention of irreversible physical and neurological complications. Genetic counselling can also be provided. This review focuses on three HMD categories: acute, treatable HMDs (urea cycle abnormalities, remethylation disorders, acute intermittent porphyria); chronic, treatable HMDs (Wilson’s disease, Niemann-Pick disease type C, homocystinuria due to cystathionine beta-synthase deficiency, cerebrotendinous xanthomatosis); and chronic HMDs that are difficult to treat (lysosomal storage diseases, X-linked adrenoleukodystrophy, creatine deficiency syndrome). We also propose an algorithm for the diagnosis of HMDs in patients with psychiatric symptoms. PMID:25478001

  14. [Adult Celiac Disease].

    PubMed

    Many, Natalie; Biedermann, Luc

    2016-07-01

    Celiac disease is an immune-mediated enteropathy in genetically predisposed individuals, triggered by gluten ingestion. Clinical manifestations include intestinal and extraintestinal symptoms. Affected individuals may also be completely asymptomatic. Nevertheless, an early diagnosis is essential in order to prevent long-term complications. Diagnostic approach involves serologic testing for tissue transglutaminase antibodies followed by duodenal biopsy in case of seropositivity. Until now, the only available treatment consists of a strict glute-free diet. Newer therapeutic strategies are currently being evaluated in clinical trials. PMID:27381303

  15. [Adult Celiac Disease].

    PubMed

    Many, Natalie; Biedermann, Luc

    2016-07-01

    Celiac disease is an immune-mediated enteropathy in genetically predisposed individuals, triggered by gluten ingestion. Clinical manifestations include intestinal and extraintestinal symptoms. Affected individuals may also be completely asymptomatic. Nevertheless, an early diagnosis is essential in order to prevent long-term complications. Diagnostic approach involves serologic testing for tissue transglutaminase antibodies followed by duodenal biopsy in case of seropositivity. Until now, the only available treatment consists of a strict glute-free diet. Newer therapeutic strategies are currently being evaluated in clinical trials.

  16. [Adult-onset rare diseases].

    PubMed

    Pfliegler, György; Kovács, Erzsébet; Kovács, György; Urbán, Krisztián; Nagy, Valéria; Brúgós, Boglárka

    2014-03-01

    The present paper is focusing on rare diseases manifesting in late childhood or adulthood. A part of these syndromes are not of genetic origin, such as relatively or absolutely rare infections, autoimmune diseases, tumours, or diseases due to rare environmental toxic agents. In addition, even a large proportion of genetic disorders may develop in adulthood or may have adult forms as well, affecting are almost each medical specialization. Examples are storage disorders (e.g. adult form of Tay-Sachs disease, Gaucher-disease), enzyme deficiencies (e.g. ornithin-transcarbamylase deficiency of the urea cycle disorders), rare thrombophilias (e.g. homozygous factor V. Leiden mutation, antithrombin deficiency), or some rare monogenic disorders such as Huntington-chorea and many others. It is now generally accepted that at least half of the 6-8000 "rare diseases" belong either to the scope of adult-care (e.g. internal medicine, neurology), or to "age-neutral" specialities such as ophtalmology, dermatology etc.). PMID:24566697

  17. Early childhood growth failure and the developmental origins of adult disease: do enteric infections and malnutrition increase risk for the metabolic syndrome?

    PubMed

    DeBoer, Mark D; Lima, Aldo A M; Oría, Reinaldo B; Scharf, Rebecca J; Moore, Sean R; Luna, Max A; Guerrant, Richard L

    2012-11-01

    Hypotheses regarding the developmental origins of health and disease postulate that developing fetuses - and potentially young children - undergo adaptive epigenetic changes that have longstanding effects on metabolism and other processes. Ongoing research explores whether these adaptations occur during early life following early childhood malnutrition. In the developing world, there remains a high degree of nutritional stunting, defined as linear growth failure caused by inadequate caloric intake, which may be exacerbated by inflammation from ongoing infections. In areas with poor sanitation, children experience vicious cycles of enteric infections and malnutrition, resulting in poor nutrient absorption as a result of changes in the intestinal mucosa, now termed "environmental enteropathy." Emerging evidence links early childhood diarrhea and/or growth failure with an increased occurrence of risk factors for cardiovascular disease in later life, including dyslipidemia, hypertension, and glucose intolerance. The mechanisms for these associations remain poorly understood and may relate to epigenetic responses to poor nutrition, increased inflammation, or both. Given the increased incidence of cardiovascular disease in developing areas of the world, associations between childhood malnutrition, early-life infections, and the increased occurrence of risk factors for cardiovascular disease underscore further reasons to improve nutrition and infection-related outcomes for young children worldwide.

  18. Heart Disease, Stroke, or Other Cardiovascular Disease and Adult Vaccination

    MedlinePlus

    ... Disease, Stroke, or Other Cardiovascular Disease and Adult Vaccination Language: English Español (Spanish) Recommend on Facebook Tweet ... more about health insurance options. Learn about adult vaccination and other health conditions Asplenia Diabetes Heart Disease, ...

  19. Opportunities for genetic improvement of metabolic diseases

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Metabolic disorders are disturbances to one or more of the metabolic processes in dairy cattle. Dysfunction of any of these processes is associated with the manifestation of metabolic diseases or disorders. In this review, data recording, incidences, genetic parameters, predictors and status of gene...

  20. Ketone body metabolism and cardiovascular disease

    PubMed Central

    Cotter, David G.; Schugar, Rebecca C.

    2013-01-01

    Ketone bodies are metabolized through evolutionarily conserved pathways that support bioenergetic homeostasis, particularly in brain, heart, and skeletal muscle when carbohydrates are in short supply. The metabolism of ketone bodies interfaces with the tricarboxylic acid cycle, β-oxidation of fatty acids, de novo lipogenesis, sterol biosynthesis, glucose metabolism, the mitochondrial electron transport chain, hormonal signaling, intracellular signal transduction pathways, and the microbiome. Here we review the mechanisms through which ketone bodies are metabolized and how their signals are transmitted. We focus on the roles this metabolic pathway may play in cardiovascular disease states, the bioenergetic benefits of myocardial ketone body oxidation, and prospective interactions among ketone body metabolism, obesity, metabolic syndrome, and atherosclerosis. Ketone body metabolism is noninvasively quantifiable in humans and is responsive to nutritional interventions. Therefore, further investigation of this pathway in disease models and in humans may ultimately yield tailored diagnostic strategies and therapies for specific pathological states. PMID:23396451

  1. Lung Disease Including Asthma and Adult Vaccination

    MedlinePlus

    ... Healthcare Professionals Lung Disease including Asthma and Adult Vaccination Language: English Español (Spanish) Recommend on Facebook Tweet ... more about health insurance options. Learn about adult vaccination and other health conditions Asplenia Diabetes Heart Disease, ...

  2. Metabolic disease network and its implication for disease comorbidity

    NASA Astrophysics Data System (ADS)

    Lee, Deok-Sun; Oltvai, Zoltan; Christakis, Nicholas; Barabasi, Albert-Laszlo

    2008-03-01

    Given that most diseases are the result of the breakdown of some cellular processes, a key aim of modern medicine is to establish the relationship between disease phenotypes and the various disruptions in the underlying cellular networks. Here we show that our current understanding of the structure of the human metabolic network can provide insight into potential relationships among often distinct disease phenotypes. Using the known enzyme-disease associations, we construct a human metabolic disease network in which nodes are diseases and two diseases are linked if the enzymes associated with them catalyze adjacent metabolic reactions. We find that the more connected a disease is, the higher is its prevalence and the chance that it is associated with a high mortality. The results indicate that the cellular network-level relationships between metabolic pathways and the associated disease provide insights into disease comorbidity, with potential important consequences on disease diagnosis and prevention.

  3. Metabolic syndrome: a child is not a small adult.

    PubMed

    Pietrobelli, Angelo; Malavolti, Marcella; Battistini, Nino C; Fuiano, Nicola

    2008-01-01

    Obesity is associated with an increased all-cause mortality rate and even small weight losses can be associated with short-term reduction in risk factors for disease. There is strong evidence that weight loss in obese subjects improves risk factors for diabetes and cardiaovascular diseases. Metabolic syndrome (MS) in adults is defined as a cluster of risk factors for cardiovascular disease and type 2 diabetes mellitus, which includes abdominal obesity, dyslipidemia, glucose intolerance and hypertension. Application of the MS concept in children and adolescents is controversial; in fact no consensus exists on a specific definition for pediatric MS. Lack of consensus is in part due to body evolution associated with childhood and puberty that is related to changes in metabolic and clinical characteristics. The aim of this article is to try to clarify the differences between the MS as a concept and the MS as a diagnostic category, as well as to develop a theory related to its pathophysiology. We comment on the relationship between obesity, regional fat distribution and the MS, and finally we offer some insights into MS methodological approaches for estimating metabolic risk-factor clustering in children and adolescents. PMID:18278635

  4. Prenatal diagnosis of inherited metabolic diseases.

    PubMed Central

    Diukman, R; Goldberg, J D

    1993-01-01

    Advances in the prenatal diagnosis of inherited metabolic disease have provided new reproductive options to at-risk couples. These advances have occurred in both sampling techniques and methods of analysis. In this review we present an overview of the currently available prenatal diagnostic approaches for the diagnosis of metabolic disease in a fetus. Images PMID:8236980

  5. Fetal origins of adult disease.

    PubMed

    Calkins, Kara; Devaskar, Sherin U

    2011-07-01

    Dr. David Barker first popularized the concept of fetal origins of adult disease (FOAD). Since its inception, FOAD has received considerable attention. The FOAD hypothesis holds that events during early development have a profound impact on one's risk for development of future adult disease. Low birth weight, a surrogate marker of poor fetal growth and nutrition, is linked to coronary artery disease, hypertension, obesity, and insulin resistance. Clues originally arose from large 20th century, European birth registries. Today, large, diverse human cohorts and various animal models have extensively replicated these original observations. This review focuses on the pathogenesis related to FOAD and examines Dr. David Barker's landmark studies, along with additional human and animal model data. Implications of the FOAD extend beyond the low birth weight population and include babies exposed to stress, both nutritional and nonnutritional, during different critical periods of development, which ultimately result in a disease state. By understanding FOAD, health care professionals and policy makers will make this issue a high health care priority and implement preventive measures and treatment for those at higher risk for chronic diseases.

  6. [Adult form of Pompe disease].

    PubMed

    Ziółkowska-Graca, Bozena; Kania, Aleksander; Zwolińska, Grazyna; Nizankowska-Mogilnicka, Ewa

    2008-01-01

    Pompe disease (glycogen-storage disease type II) is an autosomal recessive disorder caused by a deficiency of lysosomal acid alpha-glucosidase (GAA), leading to the accumulation of glycogen in the lysosomes primarily in muscle cells. In the adult form of the disease, proximal muscle weakness is noted and muscle volume is decreased. The infantile form is usually fatal. In the adult form of the disease the prognosis is relatively good. Muscle weakness may, however, interfere with normal daily activities, and respiratory insufficiency may be associated with obstructive sleep apnea. Death usually results from respiratory failure. Effective specific treatment is not available. Enzyme replacement therapy with recombinant human GAA (rh-GAA) still remains a research area. We report the case of a 24-year-old student admitted to the Department of Pulmonary Diseases because of severe respiratory insufficiency. Clinical symptoms such as dyspnea, muscular weakness and increased daytime sleepiness had been progressing for 2 years. Clinical examination and increased blood levels of CK suggested muscle pathology. Histopathological analysis of muscle biopsy, performed under electron microscope, confirmed the presence of vacuoles containing glycogen. Specific enzymatic activity of alpha-glucosidase was analyzed confirming Pompe disease. The only effective method to treat respiratory insufficiency was bi-level positive pressure ventilation. Respiratory rehabilitation was instituted and is still continued by the patient at home. A high-protein, low-sugar diet was proposed for the patient. Because of poliglobulia low molecular weight heparin was prescribed. The patient is eligible for experimental replacement therapy with rh-GAA. PMID:19003770

  7. Early childhood growth failure and the developmental origins of adult disease: Do enteric infections and malnutrition increase risk for the metabolic syndrome?

    PubMed Central

    DeBoer, Mark D.; Lima, Aldo A. M.; Oría, Reinaldo B.; Scharf, Rebecca J.; Moore, Sean R.; Luna, Max A.; Guerrant, Richard L.

    2012-01-01

    Hypotheses regarding the developmental origins of health and disease postulate that developing fetuses–and potentially young children—undergo adaptive epigenetic changes with longstanding effects on metabolism and other processes. Ongoing research explores whether these adaptations occur during early life following malnutrition. In the developing world there remains a high degree of nutritional stunting—linear growth failure due to inadequate calories that may be exacerbated by inflammation from ongoing infections. In areas with poor sanitation children experience vicious cycles of enteric infections and malnutrition, resulting in poor nutrient absorption from intestinal mucosa changes now termed “environmental enteropathy.” Emerging evidence links early childhood diarrhea and/or growth failure with increased CVD risk factors in later life, including dyslipidemia, hypertension and glucose intolerance. The mechanisms for these associations remain poorly understood and may relate to epigenetic responses to poor nutrition, increased inflammation or both. Given increases in CVD in developing areas of the world, associations between childhood malnutrition, early life infections and increased CVD risk factors underscore further reasons to improve nutrition and infection-related outcomes for young children worldwide. PMID:23110643

  8. Bariatric surgery: the indications in metabolic disease.

    PubMed

    Neff, K J; le Roux, C W

    2014-01-01

    As well as the pronounced effect on body mass index (BMI), bariatric surgery is increasingly recognized as being associated with improvements in morbidity and mortality in a range of conditions, from airways disease to cancer. In metabolic disease, the impact of bariatric surgery is particularly obvious with marked improvements in glycemic control in patients with type 2 diabetes mellitus, to the point of effecting diabetes remission in some. Hypertension and dyslipidemia, key components of the metabolic syndrome, also respond to bariatric surgery. Despite the increasing evidence of benefit in metabolic disease, the major national guidelines for selecting candidates for bariatric surgery retain their emphasis on body weight. In these guidelines, a BMI ≥35 kg/m(2) is needed to indicate surgery, even in those with profound metabolic disturbance. The recent International Diabetes Federation guidelines have identified the need to reorientate our focus from BMI to metabolic disease. In this review, we examine the developing indications for the use of bariatric surgery in metabolic disease. We will focus on type 2 diabetes mellitus and the metabolic syndrome. Within this, we will outline the data for using bariatric surgery as metabolic surgery, including those with a BMI <35 kg/m(2). PMID:23838610

  9. The Relationship between Dietary Patterns and Metabolic Health in a Representative Sample of Adult Australians

    PubMed Central

    Bell, Lucinda K.; Edwards, Suzanne; Grieger, Jessica A.

    2015-01-01

    Studies assessing dietary intake and its relationship to metabolic phenotype are emerging, but limited. The aims of the study are to identify dietary patterns in Australian adults, and to determine whether these dietary patterns are associated with metabolic phenotype and obesity. Cross-sectional data from the Australian Bureau of Statistics 2011 Australian Health Survey was analysed. Subjects included adults aged 45 years and over (n = 2415). Metabolic phenotype was determined according to criteria used to define metabolic syndrome (0–2 abnormalities vs. 3–7 abnormalities), and additionally categorized for obesity (body mass index (BMI) ≥30 kg/m2 vs. BMI <30 kg/m2). Dietary patterns were derived using factor analysis. Multivariable models were used to assess the relationship between dietary patterns and metabolic phenotype, with adjustment for age, sex, smoking status, socio-economic indexes for areas, physical activity and daily energy intake. Twenty percent of the population was metabolically unhealthy and obese. In the fully adjusted model, for every one standard deviation increase in the Healthy dietary pattern, the odds of having a more metabolically healthy profile increased by 16% (odds ratio (OR) 1.16; 95% confidence interval (CI): 1.04, 1.29). Poor metabolic profile and obesity are prevalent in Australian adults and a healthier dietary pattern plays a role in a metabolic and BMI phenotypes. Nutritional strategies addressing metabolic syndrome criteria and targeting obesity are recommended in order to improve metabolic phenotype and potential disease burden. PMID:26251918

  10. Circadian rhythms in liver metabolism and disease.

    PubMed

    Ferrell, Jessica M; Chiang, John Y L

    2015-03-01

    Mounting research evidence demonstrates a significant negative impact of circadian disruption on human health. Shift work, chronic jet lag and sleep disturbances are associated with increased incidence of metabolic syndrome, and consequently result in obesity, type 2 diabetes and dyslipidemia. Here, these associations are reviewed with respect to liver metabolism and disease.

  11. Circadian rhythms in liver metabolism and disease.

    PubMed

    Ferrell, Jessica M; Chiang, John Y L

    2015-03-01

    Mounting research evidence demonstrates a significant negative impact of circadian disruption on human health. Shift work, chronic jet lag and sleep disturbances are associated with increased incidence of metabolic syndrome, and consequently result in obesity, type 2 diabetes and dyslipidemia. Here, these associations are reviewed with respect to liver metabolism and disease. PMID:26579436

  12. Adult neurogenesis in Parkinson's disease.

    PubMed

    Marxreiter, Franz; Regensburger, Martin; Winkler, Jürgen

    2013-02-01

    Parkinson's disease (PD), the second most common neurodegenerative disorder, affects 1-2 % of humans aged 60 years and older. The diagnosis of PD is based on motor symptoms such as bradykinesia, rigidity, tremor, and postural instability associated with the striatal dopaminergic deficit that is linked to neurodegenerative processes in the substantia nigra (SN). In the past, cellular replacement strategies have been evaluated for their potential to alleviate these symptoms. Adult neurogenesis, the generation of new neurons within two proliferative niches in the adult brain, is being intensively studied as one potential mode for cell-based therapies. The subventricular zone provides new neurons for the olfactory bulb functionally contributing to olfaction. The subgranular zone of the hippocampus produces new granule neurons for the dentate gyrus, required for memory formation and proper processing of anxiety provoking stimuli. Recent years have revealed that PD is associated with non-motor symptoms such as hyposmia, anhedonia, lack of novelty seeking behavior, depression, and anxiety that are not directly associated with neurodegenerative processes in the SN. This broad spectrum of non-motor symptoms may partly rely on proper olfactorial processing and hippocampal function. Therefore, it is conceivable that some non-motor deficits in PD are related to defective adult neurogenesis. Accordingly, in animal models and postmortem studies of PD, adult neurogenesis is severely affected, although the exact mechanisms and effects of these changes are not yet fully understood or are under debate due to conflicting results. Here, we review the current concepts related to the dynamic interplay between endogenous cellular plasticity and PD-associated pathology.

  13. Prevalence of metabolic syndrome in Brazilian adults: a systematic review

    PubMed Central

    2013-01-01

    Background The metabolic syndrome (MS) is a complex of risk factors for cardiovascular disease. This syndrome increases the risk of diabetes, cardiovascular disease and all-cause mortality. It has been demonstrated that the prevalence of MS is increasing worldwide. Despite the importance of MS in the context of metabolic and cardiovascular disease, few studies have described the prevalence of MS and its determinants in Latin America. The present study aims to assess studies describing the prevalence of MS in Brazil in order to determine the global prevalence of the syndrome and its components. Methods Systematic review. Searches were carried out in PubMed and Scielo from the earliest available online indexing year through May 2013. There were no restrictions on language. The search terms used to describe MS were taken from the PubMed (MeSH) dictionary: “metabolic syndrome x”, “prevalence” and “Brazil”. Studies were included if they were cross-sectional, described the prevalence of MS and were conducted in apparently healthy subjects, from the general population, 19-64 years old (adult and middle aged) of both genders. The titles and abstracts of all the articles identified were screened for eligibility. Results Ten cross-sectional studies were selected. The weighted mean for general prevalence of MS in Brazil was 29.6% (range: 14.9%-65.3%). Half of the studies used the criteria for clinical diagnosis of MS proposed by the National Cholesterol Education Program Adult Treatment Panel III (NCEP-ATP III) (2001). The highest prevalence of MS (65.3%) was found in a study conducted in an indigenous population, whereas the lowest prevalence of MS (14.9%) was reported in a rural area. The most frequent MS components were low HDL-cholesterol (59.3%) and hypertension (52.5%). Conclusions Despite methodological differences among the studies selected, our findings suggested a high prevalence of MS in the Brazilian adult population. PMID:24350922

  14. Metabolic Disturbances in Diseases with Neurological Involvement

    PubMed Central

    Duarte, João M. N.; Schuck, Patrícia F.; Wenk, Gary L.; Ferreira, Gustavo C.

    2014-01-01

    Degeneration of specific neuronal populations and progressive nervous system dysfunction characterize neurodegenerative diseases, including Alzheimer’s disease and Parkinson’s disease. These findings are also reported in inherited diseases such as phenylketonuria and glutaric aciduria type I. The involvement of mitochondrial dysfunction in these diseases was reported, elicited by genetic alterations, exogenous toxins or buildup of toxic metabolites. In this review we shall discuss some metabolic alterations related to the pathophysiology of diseases with neurological involvement and aging process. These findings may help identifying early disease biomarkers and lead to more effective therapies to improve the quality of life of the patients affected by these devastating illnesses. PMID:25110608

  15. Metabolic reprogramming: a new relevant pathway in adult adrenocortical tumors

    PubMed Central

    Longatto-Filho, Adhemar; Faria, André M.; Fragoso, Maria C. B. V.; Lovisolo, Silvana M.; Lerário, Antonio M.; Almeida, Madson Q.

    2015-01-01

    Adrenocortical carcinomas (ACCs) are complex neoplasias that may present unexpected clinical behavior, being imperative to identify new biological markers that can predict patient prognosis and provide new therapeutic options. The main aim of the present study was to evaluate the prognostic value of metabolism-related key proteins in adrenocortical carcinoma. The immunohistochemical expression of MCT1, MCT2, MCT4, CD147, CD44, GLUT1 and CAIX was evaluated in a series of 154 adult patients with adrenocortical neoplasia and associated with patients' clinicopathological parameters. A significant increase in was found for membranous expression of MCT4, GLUT1 and CAIX in carcinomas, when compared to adenomas. Importantly MCT1, GLUT1 and CAIX expressions were significantly associated with poor prognostic variables, including high nuclear grade, high mitotic index, advanced tumor staging, presence of metastasis, as well as shorter overall and disease free survival. In opposition, MCT2 membranous expression was associated with favorable prognostic parameters. Importantly, cytoplasmic expression of CD147 was identified as an independent predictor of longer overall survival and cytoplasmic expression of CAIX as an independent predictor of longer disease-free survival. We provide evidence for a metabolic reprogramming in adrenocortical malignant tumors towards the hyperglycolytic and acid-resistant phenotype, which was associated with poor prognosis. PMID:26587828

  16. Evaluation of metabolic syndrome in adults of Talca city, Chile

    PubMed Central

    Mujica, Veronica; Leiva, Elba; Icaza, Gloria; Diaz, Nora; Arredondo, Miguel; Moore-Carrasco, Rodrigo; Orrego, Roxana; Vásquez, Marcela; Palomo, Ivan

    2008-01-01

    Objective- Insulin resistance (IR) is an important risk factor for type 2 Diabetes Mellitus (DM2) and cardiovascular disease (CVD). Metabolic Syndrome (MS) is a clustering of metabolic alterations associated to IR; however, there is no international consensus for defining its diagnosis. Our objective was to evaluate the prevalence and characteristics of MS identified by the ATP III and IDF criteria in adults from Talca city. Research and methods- We studied 1007 individuals, aged 18–74, and residents from Talca. MS subjects were defined according to ATP III (three altered factors) and IDF criteria (patients with waist circumference >80/90 cm (W/M) and two others altered factors). Results- The prevalence of metabolic syndrome according to the IDF and ATP III criteria was 36.4% and 29.5%, respectively after adjustment for age and sex. The agreement for both criteria was 89%. The prevalence in men was higher than in women for both MS definitions, although not significant. MS probability increased with age, and the highest risk was in the 57–68 age group (ATP-MS) and 53–72 age group (IDF-MS). Hypertension, high triglycerides and abdominal obesity are the most frequent alterations in MS. Conclusion- MS prevalence in adults was higher when diagnosed with IDF than with ATP criterion; in both, age is directly related with the MS presence. The MS subjects showed higher levels of blood pressure, waist circumference and plasma triglycerides. Considering our results, it is worrisome that one third of our population has a high risk of developing DM2 and CVD in the future. PMID:18482457

  17. Cancer as a mitochondrial metabolic disease

    PubMed Central

    Seyfried, Thomas N.

    2015-01-01

    Cancer is widely considered a genetic disease involving nuclear mutations in oncogenes and tumor suppressor genes. This view persists despite the numerous inconsistencies associated with the somatic mutation theory. In contrast to the somatic mutation theory, emerging evidence suggests that cancer is a mitochondrial metabolic disease, according to the original theory of Otto Warburg. The findings are reviewed from nuclear cytoplasm transfer experiments that relate to the origin of cancer. The evidence from these experiments is difficult to reconcile with the somatic mutation theory, but is consistent with the notion that cancer is primarily a mitochondrial metabolic disease. PMID:26217661

  18. A clinical perspective of obesity, metabolic syndrome and cardiovascular disease.

    PubMed

    Han, Thang S; Lean, Mike Ej

    2016-01-01

    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. PMID:26998259

  19. A clinical perspective of obesity, metabolic syndrome and cardiovascular disease

    PubMed Central

    Lean, Mike EJ

    2016-01-01

    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/m2 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. PMID:26998259

  20. [Metabolic correction: a biochemical option against diseases].

    PubMed

    Miranda-Massari, Jorge R; González, Michael J; Rodriguez-Gomez, José R; Duconge, Jorge; Allende-Vigo, Myriam Z; Jiménez Ramirez, Francisco J; Cintrón, Kenneth; Ricart, Carlos; Zaragoza-Urdaz, Rafael; Berdiel, Miguel Jabbar; Vázquez, Alex

    2015-01-01

    Human development and its physiology depends on a number of complex biochemical body processes, many of which are interactive and codependent. The speed and the degree in which many physiological reactions are completed depend on enzyme activity, which in turn depends on the bioavailability of co-factors and micronutrients such as vitamins and minerals. To achieve a healthy physiological state, organism need that biochemical reactions occur in a controlled and specific way at a particular speed and level or grade fully completed. To achieve this, is required an optimal metabolic balance. Factors such as, a particular genetic composition, inadequate dietary consumption patterns, traumas, diseases, toxins and environmental stress all of these factors rising demands for nutrients in order to obtain optimal metabolic balance. Metabolic correction is a biochemical and physiological concept that explains how improvements in cellular biochemistry of an organism can help the body achieve metabolic and physiological optimization. We summarize the contribution of several pioneers in understanding the role of micronutrients in health management. The concept of metabolic correction is becoming a significant term due to the presence of genetic variants that affect the speed of reactions of enzymes, causing metabolic alterations that enhance or promote the state/development of multiple diseases. Decline in the nutritional value of the food we eat, the increase in demand for certain nutrients caused by normal development, diseases and medications induce, usually, nutrients consumption. These nutritional deficiencies and insufficiencies are causing massive economic costs due to increased morbidity and mortality in our society. In summary, metabolic correction improves the enzymatic function, which favors the physiological normal functions, thus, contributing to improving health and the welfare of the human being. The purpose of this paper is to describe and introduce the concept

  1. Candy consumption was not associated with body weight measures, risk factors for cardiovascular disease, or metabolic syndrome in US adults: NHANES 1999-2004

    Technology Transfer Automated Retrieval System (TEKTRAN)

    There is limited research examining the relationship of candy consumption by adults on diet and health. The purpose of this study was to determine total, chocolate, or sugar candy consumption and their effect on energy, saturated fatty acid and added sugar intake, weight, risk factors for cardiovasc...

  2. Chronic kidney disease and bone metabolism.

    PubMed

    Kazama, Junichiro James; Matsuo, Koji; Iwasaki, Yoshiko; Fukagawa, Masafumi

    2015-05-01

    Chronic kidney disease-related mineral and bone disease (CKD-MBD) is a syndrome defined as a systemic mineral metabolic disorder associated with CKD, and the term renal osteodystrophy indicates a pathomorphological concept of bone lesions associated with CKD-MBD. Cortical bone thinning, abnormalities in bone turnover and primary/secondary mineralization, elevated levels of circulating sclerostin, increased apoptosis in osteoblasts and osteocytes, disturbance of the coupling phenomenon, iatrogenic factors, accumulated micro-crackles, crystal/collagen disorientation, and chemical modification of collagen crosslinks are all possible candidates found in CKD that could promote osteopenia and/or bone fragility. Some of above factors are the consequences of abnormal systemic mineral metabolism but for others it seem unlikely. We have used the term uremic osteoporosis to describe the uremia-induced bone fragility which is not derived from abnormal systemic mineral metabolism. Interestingly, the disease aspect of uremic osteoporosis appears to be similar to that of senile osteoporosis. PMID:25653092

  3. Alcohol-Induced Developmental Origins of Adult-Onset Diseases.

    PubMed

    Lunde, Emilie R; Washburn, Shannon E; Golding, Michael C; Bake, Shameena; Miranda, Rajesh C; Ramadoss, Jayanth

    2016-07-01

    Fetal alcohol exposure may impair growth, development, and function of multiple organ systems and is encompassed by the term fetal alcohol spectrum disorders (FASD). Research has so far focused on the mechanisms, prevention, and diagnosis of FASD, while the risk for adult-onset chronic diseases in individuals exposed to alcohol in utero is not well explored. David Barker's hypothesis on Developmental Origins of Health and Disease (DOHaD) suggests that insults to the milieu of the developing fetus program it for adult development of chronic diseases. In the 25 years since the introduction of this hypothesis, epidemiological and animal model studies have made significant advancements in identifying in utero developmental origins of chronic adult-onset diseases affecting cardiovascular, endocrine, musculoskeletal, and psychobehavioral systems. Teratogen exposure is an established programming agent for adult diseases, and recent studies suggest that prenatal alcohol exposure correlates with adult onset of neurobehavioral deficits, cardiovascular disease, endocrine dysfunction, and nutrient homeostasis instability, warranting additional investigation of alcohol-induced DOHaD, as well as patient follow-up well into adulthood for affected individuals. In utero epigenetic alterations during critical periods of methylation are a key potential mechanism for programming and susceptibility of adult-onset chronic diseases, with imprinted genes affecting metabolism being critical targets. Additional studies in epidemiology, phenotypic characterization in response to timing, dose, and duration of exposure, as well as elucidation of mechanisms underlying FASD-DOHaD inter relation, are thus needed to clinically define chronic disease associated with prenatal alcohol exposure. These studies are critical to establish interventional strategies that decrease incidence of these adult-onset diseases and promote healthier aging among individuals affected with FASD. PMID:27254466

  4. Alcohol-Induced Developmental Origins of Adult-Onset Diseases.

    PubMed

    Lunde, Emilie R; Washburn, Shannon E; Golding, Michael C; Bake, Shameena; Miranda, Rajesh C; Ramadoss, Jayanth

    2016-07-01

    Fetal alcohol exposure may impair growth, development, and function of multiple organ systems and is encompassed by the term fetal alcohol spectrum disorders (FASD). Research has so far focused on the mechanisms, prevention, and diagnosis of FASD, while the risk for adult-onset chronic diseases in individuals exposed to alcohol in utero is not well explored. David Barker's hypothesis on Developmental Origins of Health and Disease (DOHaD) suggests that insults to the milieu of the developing fetus program it for adult development of chronic diseases. In the 25 years since the introduction of this hypothesis, epidemiological and animal model studies have made significant advancements in identifying in utero developmental origins of chronic adult-onset diseases affecting cardiovascular, endocrine, musculoskeletal, and psychobehavioral systems. Teratogen exposure is an established programming agent for adult diseases, and recent studies suggest that prenatal alcohol exposure correlates with adult onset of neurobehavioral deficits, cardiovascular disease, endocrine dysfunction, and nutrient homeostasis instability, warranting additional investigation of alcohol-induced DOHaD, as well as patient follow-up well into adulthood for affected individuals. In utero epigenetic alterations during critical periods of methylation are a key potential mechanism for programming and susceptibility of adult-onset chronic diseases, with imprinted genes affecting metabolism being critical targets. Additional studies in epidemiology, phenotypic characterization in response to timing, dose, and duration of exposure, as well as elucidation of mechanisms underlying FASD-DOHaD inter relation, are thus needed to clinically define chronic disease associated with prenatal alcohol exposure. These studies are critical to establish interventional strategies that decrease incidence of these adult-onset diseases and promote healthier aging among individuals affected with FASD.

  5. Association between metabolic syndrome and subclinical coronary atherosclerosis in asymptomatic adults.

    PubMed

    Kullo, Iftikhar J; Cassidy, Andrea E; Peyser, Patricia A; Turner, Stephen T; Sheedy, Patrick F; Bielak, Lawrence F

    2004-12-15

    Metabolic syndrome was associated with the presence and quantity of coronary artery calcium, a marker of subclinical coronary atherosclerosis, in 1,129 asymptomatic adults, ages 20 to 79 years, from a community-based study. The association was independent of 10-year risk of coronary heart disease based on the Framingham risk score.

  6. Contribution of Macrophage Polarization to Metabolic Diseases.

    PubMed

    Komohara, Yoshihiro; Fujiwara, Yukio; Ohnishi, Koji; Shiraishi, Daisuke; Takeya, Motohiro

    2016-01-01

    Macrophage activation is one of the major immunological events in the pathogenesis of various diseases. Recent studies have disclosed that complicated mechanisms are involved in macrophage activation and polarization, and many published research articles have been based on the M1/M2 polarization concept. It is considered that M1- and M2-like macrophages are associated with T helper (Th)1-type and Th2-type immune responses, respectively, via several immune mediators. In this article, we summarize the correlations between macrophage polarization and metabolic disorders in both humans and mice and discuss the contribution of macrophage polarization to the pathogenic process of metabolic diseases.

  7. Metabolic bone disease in gut diseases.

    PubMed

    Lipkin, E W

    1998-06-01

    A wide spectrum of gastrointestinal illnesses impairs bone health and can result in bone pain, demineralization, and fracture. This article summarizes current knowledge of the skeletal pathology exhibited in patients with diseases of the liver, biliary tree, pancreas, and bowel. Mechanisms responsible for these syndromes and treatment options are discussed. This article enhances the practicing gastroenterologist's knowledge of the implications of gastrointestinal illness for bone. PMID:9650030

  8. Clinical presentation of metabolic liver disease.

    PubMed

    Odievre, M

    1991-01-01

    Some clinical clues should alert paediatricians to the possibility of metabolic liver diseases. They can be classified into three categories: (i) Manifestations due to hepatocellular necrosis, acute or subacute, which can reveal galactosaemia, hereditary fructose intolerance, tyrosinaemia type I, Wilson disease and alpha 1-antitrypsin deficiency. Symptoms and signs suggestive of Reye syndrome should lead to a study of fatty acid oxidation and urea cycle enzymes. All these manifestations may necessitate a rapid diagnosis and treatment when liver dysfunction is severe. (ii) Cholestatic jaundice can reveal alpha 1-antitrypsin deficiency, Byler's disease, cystic fibrosis, Niemann-Pick disease and some disorders of peroxisome biogenesis. (iii) Hepatomegaly can reveal disorders with liver damage but also storage diseases such as glycogen storage diseases, cholesteryl ester storage disease and, when associated with splenomegaly, lysosomal storage diseases. Appropriate investigations for recognizing all these entities are proposed.

  9. Fetal programming, epigenetics, and adult onset disease.

    PubMed

    Lane, Robert H

    2014-12-01

    How early life events program adult disease is undergoing a transition from the broad field of maternal malnutrition to the current relevant issues of food deserts and prematurity. Although many adult diseases and morbidities associate with various early life events and programming, the morbidities of insulin resistance, cardiovascular disease, and obesity seem to be common end points of many early life events despite potential confounders.

  10. Neurodegenerative disorders and metabolic disease.

    PubMed

    Pierre, Germaine

    2013-08-01

    Most genetic causes of neurodegenerative disorders in childhood are due to neurometabolic disease. There are over 200 disorders, including aminoacidopathies, creatine disorders, mitochondrial cytopathies, peroxisomal disorders and lysosomal storage disorders. However, diagnosis can pose a challenge to the clinician when patients present with non-specific problems like epilepsy, developmental delay, autism, dystonia and ataxia. The variety of specialist tests involved can also be daunting. This review aims to give a practical approach to the investigation and diagnosis of neurometabolic disease from the neonatal period to late childhood while prioritising disorders where there are therapeutic options. In particular, patients who have a complex clinical picture of several neurological and non-neurological features should be investigated.

  11. Metabolomics reveals metabolic biomarkers of Crohn's disease

    SciTech Connect

    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.

  12. Depression in adult patients with biotin responsive basal ganglia disease.

    PubMed

    Bubshait, Dalal K; Rashid, Asif; Al-Owain, Mohammed A; Sulaiman, Raashda A

    2016-01-01

    Biotin responsive basal ganglia disease (BBGD), is a potentially treatable inherited metabolic disorder which clinically presents as sub-acute encephalopathy in children. Early diagnosis and treatment of this disorder results in good clinical recovery in childhood. However, there is no report in the literature on the long term outcome of these treated patients in adult life. We report two patients with BBGD who were metabolically stable on treatment and developed depression later in life. These cases highlight the association of depression with basal ganglia disorders and demonstrate that depression is the potential long term complication of BBGD.

  13. Metabolic bone diseases in kidney transplant recipients.

    PubMed

    Zhang, Rubin; Chouhan, Kanwaljit K

    2012-10-01

    Metabolic bone disease after kidney transplantation has a complex pathophysiology and heterogeneous histology. Pre-existing renal osteodystrophy may not resolve completely, but continue or evolve into a different osteodystrophy. Rapid bone loss immediately after transplant can persist, at a lower rate, for years to come. These greatly increase the risk of bone fracture and vertebral collapse. Each patient may have multiple risk factors of bone loss, such as steroids usage, hypogonadism, persistent hyperparathyroidism (HPT), poor allograft function, metabolic acidosis, hypophosphatemia, vitamin D deficiency, aging, immobility and chronic disease. Clinical management requires a comprehensive approach to address the underlying and ongoing disease processes. Successful prevention of bone loss has been shown with vitamin D, bisphosphonates, calcitonin as well as treatment of hypogonadism and HPT. Novel approach to restore the normal bone remodeling and improve the bone quality may be needed in order to effectively decrease bone fracture rate in kidney transplant recipients. PMID:24175250

  14. [Serum sclerostin levels and metabolic bone diseases].

    PubMed

    Yamauchi, Mika; Sugimoto, Toshitsugu

    2013-06-01

    Serum sclerostin levels are being investigated in various metabolic bone diseases. Since serum sclerostin levels are decreased in primary hyperparathyroidism and elevated in hypoparathyroidism, parathyroid hormone (PTH) is thought to be a regulatory factor for sclerostin. Serum sclerostin levels exhibit a significant positive correlation with bone mineral density. On the other hand, a couple of studies on postmenopausal women have shown that high serum sclerostin levels are a risk factor for fracture. Although glucocorticoid induced osteoporosis and diabetes are both diseases that reduce bone formation, serum sclerostin levels have been reported to be decreased in the former and elevated in the latter, suggesting differences in the effects of sclerostin in the two diseases. Serum sclerostin levels are correlated with renal function, and increase with reduction in renal function. Serum sclerostin level may be a new index of bone assessment that differs from bone mineral density and bone metabolic markers.

  15. Obesity, metabolic health, and mortality in adults: a nationwide population-based study in Korea.

    PubMed

    Yang, Hae Kyung; Han, Kyungdo; Kwon, Hyuk-Sang; Park, Yong-Moon; Cho, Jae-Hyoung; Yoon, Kun-Ho; Kang, Moo-Il; Cha, Bong-Yun; Lee, Seung-Hwan

    2016-01-01

    BMI, metabolic health status, and their interactions should be considered for estimating mortality risk; however, the data are controversial and unknown in Asians. We aimed to investigate this issue in Korean population. Total 323175 adults were followed-up for 96 (60-120) (median [5-95%]) months in a nationwide population-based cohort study. Participants were classified as "obese" (O) or "non-obese" (NO) using a BMI cut-off of 25 kg/m(2). People who developed ≥1 metabolic disease component (hypertension, diabetes, dyslipidaemia) in the index year were considered "metabolically unhealthy" (MU), while those with none were considered "metabolically healthy" (MH). The MUNO group had a significantly higher risk of all-cause (hazard ratio, 1.28 [95% CI, 1.21-1.35]) and cardiovascular (1.88 [1.63-2.16]) mortality, whereas the MHO group had a lower mortality risk (all-cause: 0.81 [0.74-0.88]), cardiovascular: 0.73 [0.57-0.95]), compared to the MHNO group. A similar pattern was noted for cancer and other-cause mortality. Metabolically unhealthy status was associated with higher risk of all-cause and cardiovascular mortality regardless of BMI levels, and there was a dose-response relationship between the number of incident metabolic diseases and mortality risk. In conclusion, poor metabolic health status contributed more to mortality than high BMI did, in Korean adults. PMID:27445194

  16. Adipocytokines in obesity and metabolic disease.

    PubMed

    Cao, Haiming

    2014-02-01

    The current global obesity pandemic is the leading cause for the soaring rates of metabolic diseases, especially diabetes, cardiovascular disease, hypertension, and non-alcoholic hepatosteatosis. Efforts devoted to find cures for obesity and associated disorders in the past two decades have prompted intensive interest in adipocyte biology, and have led to major advances in the mechanistic understanding of adipose tissue as an essential endocrine organ. Adipose tissue secretes an array of hormones (adipokines) that signal key organs to maintain metabolic homeostasis, and their dysfunction has been causally linked to a wide range of metabolic diseases. In addition, obesity induces production of inflammatory cytokines (often referred to together with adipokines as adipocytokines) and infiltration of immune cells into adipose tissue, which creates a state of chronic low-grade inflammation. Metabolic inflammation has been increasingly recognized as a unifying mechanism linking obesity to a broad spectrum of pathological conditions. This review focuses on classic examples of adipocytokines that have helped to form the basis of the endocrine and inflammatory roles of adipose tissue, and it also details a few newly characterized adipocytokines that provide fresh insights into adipose biology. Studies of adipocytokines in clinical settings and their therapeutic potential are also discussed.

  17. Cerebral glucose metabolism in Parkinson's disease.

    PubMed

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

    1984-02-01

    Local cerebral glucose utilization was measured in patients with predominantly unilateral Parkinson's disease using 18F-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.

  18. Fetal programming of adult disease: implications for prenatal care.

    PubMed

    Lau, Christopher; Rogers, John M; Desai, Mina; Ross, Michael G

    2011-04-01

    The obesity epidemic, including a marked increase in the prevalence of obesity among pregnant women, represents a critical public health problem in the United States and throughout the world. Over the past two decades, it has been increasingly recognized that the risk of adult health disorders, particularly metabolic syndrome, can be markedly influenced by prenatal and infant environmental exposures (ie, developmental programming). Low birth weight, together with infant catch-up growth, is associated with a significant risk of adult obesity and cardiovascular disease, as well as adverse effects on pulmonary, renal, and cerebral function. Conversely, exposure to maternal obesity or high birth weight also represents an increased risk for childhood and adult obesity. In addition, fetal exposure to select chemicals (eg, phytoestrogens) or environmental pollutants (eg, tobacco smoke) may affect the predisposition to adult disease. Animal models have confirmed human epidemiologic findings and provided insight into putative programming mechanisms, including altered organ development, cellular signaling responses, and epigenetic modifications (ie, control of gene expression without modification of DNA sequence). Prenatal care is transitioning to incorporate goals of optimizing maternal, fetal, and neonatal health to prevent or reduce adult-onset diseases. Guidelines regarding optimal pregnancy nutrition and weight gain, management of low- and high-fetal-weight pregnancies, use of maternal glucocorticoids, and newborn feeding strategies, among others, have yet to fully integrate long-term consequences on adult health.

  19. Metabolic therapy: lessons from liver diseases.

    PubMed

    Garcia-Ruiz, Carmen; Marí, Montserrat; Colell, Anna; Morales, Albert; Fernandez-Checa, Jose C

    2011-12-01

    Fatty liver disease is one of most prevalent metabolic liver diseases, which includes alcoholic (ASH) and nonalcoholic steatohepatitis (NASH). Its initial stage is characterized by fat accumulation in the liver, that can progress to steatohepatitis, a stage of the disease in which steatosis is accompanied by inflammation, hepatocellular death, oxidative stress and fibrosis. Recent evidence in experimental models as well as in patients with steatohepatitis have uncovered a role for cholesterol and sphingolipids, particularly ceramide, in the transition from steatosis to steatohepatitis, insulin resistance and hence disease progression. Cholesterol accumulation and its trafficking to mitochondria sensitizes fatty liver to subsequent hits including inflammatory cytokines, such as TNF/Fas, in a pathway involving ceramide generation by acidic sphingomyelinase (ASMase). Thus, targeting both cholesterol and/or ASMase may represent a novel therapeutic approach of relevance in ASH and NASH, two of the most common forms of liver diseases worldwide. PMID:21933146

  20. Metabolic effects of a 13-weeks lifestyle intervention in older adults: The Growing Old Together Study

    PubMed Central

    Stassen, Stephanie A.M.; van den Akker, Erik B.; van Heemst, Diana; Dibbets-Schneider, Petra; van Dipten-van der Veen, Regina. A.; Kelderman, Milou; Hankemeier, Thomas; Mooijaart, Simon P.; van der Grond, Jeroen; Houwing-Duistermaat, Jeanine J.; Beekman, Marian; Feskens, Edith J.M.; Slagboom, P. Eline

    2016-01-01

    For people in their 40s and 50s, lifestyle programs have been shown to improve metabolic health. For older adults, however, it is not clear whether these programs are equally healthy. In the Growing Old Together study, we applied a 13-weeks lifestyle program, with a target of 12.5% caloric restriction and 12.5% increase in energy expenditure through an increase in physical activity, in 164 older adults (mean age=63.2 years; BMI=23-35 kg/m2). Mean weight loss was 4.2% (SE=2.8%) of baseline weight, which is comparable to a previous study in younger adults. Fasting insulin levels, however, showed a much smaller decrease (0.30 mU/L (SE=3.21)) and a more heterogeneous response (range=2.0-29.6 mU/L). Many other parameters of metabolic health, such as blood pressure, and thyroid, glucose and lipid metabolism improved significantly. Many 1H-NMR metabolites changed in a direction previously associated with a low risk of type 2 diabetes and cardiovascular disease and partially independently of weight loss. In conclusion, 25% reduction in energy balance for 13 weeks induced a metabolic health benefit in older adults, monitored by traditional and novel metabolic markers. PMID:26824634

  1. Interstitial lung disease - adults - discharge

    MedlinePlus

    Diffuse parenchymal lung disease - discharge; Alveolitis - discharge; Idiopathic pulmonary pneumonitis - discharge; IPP - discharge; Chronic interstitial lung - discharge; Chronic respiratory interstitial lung - ...

  2. Metabolic disorders associated with obstructive sleep apnea in adults.

    PubMed

    Lurie, Alain

    2011-01-01

    The relationship between metabolic disorders and obstructive sleep apnea (OSA) is multidirectional. Obesity is recognized as the strongest risk factor for OSA. It is unknown whether metabolic syndrome and insulin resistance/type 2 diabetes mellitus contribute to the development or aggravation of OSA, although this is likely. Conversely, OSA may be a risk factor for metabolic disorders. Strong evidence suggests that OSA may increase the risk of developing insulin resistance, glucose intolerance and type 2 diabetes mellitus. OSA has also been associated with the development and/or aggravation of obesity, dyslipidemia, metabolic syndrome and nonalcoholic fatty liver disease - a liver manifestation of metabolic syndrome. In addition, metabolic disorders are confounding factors in OSA. Metabolic disorders and OSA share common intermediate pathogenic pathways, including alterations in autonomic nervous system regulation, increased inflammatory activity, and alterations in adipokine levels and endothelial dysfunction, which may be involved in the interplay between these conditions. Overall, this complexity makes it especially difficult to reveal and understand the links between OSA and metabolic and cardiovascular disorders. The International Diabetes Federation has recently published clinical practice recommendations suggesting that OSA patients should be routinely screened for markers of metabolic disturbance and cardiovascular risk, such as waist circumference, blood pressure, and fasting lipid and glucose levels. It also recommends that the possibility of OSA should be considered in the assessment of all patients with type 2 diabetes mellitus and metabolic syndrome. PMID:22005190

  3. Glutathione Metabolism and Parkinson’s Disease

    PubMed Central

    Smeyne, Michelle

    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 this relates to protection of dopaminergic neurons from oxidative damage and its therapeutic potential in Parkinson’s disease. PMID:23665395

  4. Lipoproteins and lipoprotein metabolism in periodontal disease

    PubMed Central

    Griffiths, Rachel; Barbour, Suzanne

    2010-01-01

    A growing body of evidence indicates that the incidence of atherosclerosis is increased in subjects with periodontitis – a chronic infection of the oral cavity. This article summarizes the evidence that suggests periodontitis shifts the lipoprotein profile to be more proatherogenic. LDL-C is elevated in periodontitis and most studies indicate that triglyceride levels are also increased. By contrast, antiatherogenic HDL tends to be low in periodontitis. Periodontal therapy tends to shift lipoprotein levels to a healthier profile and also reduces subclinical indices of atherosclerosis. In summary, periodontal disease alters lipoprotein metabolism in ways that could promote atherosclerosis and cardiovascular disease. PMID:20835400

  5. The Intestinal Microbiota in Metabolic Disease

    PubMed Central

    Woting, Anni; Blaut, Michael

    2016-01-01

    Gut bacteria exert beneficial and harmful effects in metabolic diseases as deduced from the comparison of germfree and conventional mice and from fecal transplantation studies. Compositional microbial changes in diseased subjects have been linked to adiposity, type 2 diabetes and dyslipidemia. Promotion of an increased expression of intestinal nutrient transporters or a modified lipid and bile acid metabolism by the intestinal microbiota could result in an increased nutrient absorption by the host. The degradation of dietary fiber and the subsequent fermentation of monosaccharides to short-chain fatty acids (SCFA) is one of the most controversially discussed mechanisms of how gut bacteria impact host physiology. Fibers reduce the energy density of the diet, and the resulting SCFA promote intestinal gluconeogenesis, incretin formation and subsequently satiety. However, SCFA also deliver energy to the host and support liponeogenesis. Thus far, there is little knowledge on bacterial species that promote or prevent metabolic disease. Clostridium ramosum and Enterococcus cloacae were demonstrated to promote obesity in gnotobiotic mouse models, whereas bifidobacteria and Akkermansia muciniphila were associated with favorable phenotypes in conventional mice, especially when oligofructose was fed. How diet modulates the gut microbiota towards a beneficial or harmful composition needs further research. Gnotobiotic animals are a valuable tool to elucidate mechanisms underlying diet–host–microbe interactions. PMID:27058556

  6. The Intestinal Microbiota in Metabolic Disease.

    PubMed

    Woting, Anni; Blaut, Michael

    2016-01-01

    Gut bacteria exert beneficial and harmful effects in metabolic diseases as deduced from the comparison of germfree and conventional mice and from fecal transplantation studies. Compositional microbial changes in diseased subjects have been linked to adiposity, type 2 diabetes and dyslipidemia. Promotion of an increased expression of intestinal nutrient transporters or a modified lipid and bile acid metabolism by the intestinal microbiota could result in an increased nutrient absorption by the host. The degradation of dietary fiber and the subsequent fermentation of monosaccharides to short-chain fatty acids (SCFA) is one of the most controversially discussed mechanisms of how gut bacteria impact host physiology. Fibers reduce the energy density of the diet, and the resulting SCFA promote intestinal gluconeogenesis, incretin formation and subsequently satiety. However, SCFA also deliver energy to the host and support liponeogenesis. Thus far, there is little knowledge on bacterial species that promote or prevent metabolic disease. Clostridium ramosum and Enterococcus cloacae were demonstrated to promote obesity in gnotobiotic mouse models, whereas bifidobacteria and Akkermansia muciniphila were associated with favorable phenotypes in conventional mice, especially when oligofructose was fed. How diet modulates the gut microbiota towards a beneficial or harmful composition needs further research. Gnotobiotic animals are a valuable tool to elucidate mechanisms underlying diet-host-microbe interactions. PMID:27058556

  7. Calcium metabolism in adult outpatients with epilepsy receiving long-term anticonvulsant therapy

    PubMed Central

    Pylypchuk, G.; Oreopoulos, D.G.; Wilson, D.R.; Harrison, J.E.; McNeill, K.G.; Meema, H.E.; Ogilvie, R.; Sturtridge, W.C.; Murray, T.M.

    1978-01-01

    Long-term anticonvulsant drug therapy may lead to abnormalities of calcium metabolism resulting in osteomalacia. The prevalence and severity of altered calcium metabolism was studied in an adult outpatient population of persons with epilepsy receiving anticonvulsant therapy for a minimum of 2 years. Assessment of calcium metabolism was based on serum concentrations of calcium, phosphorus, alkaline phosphatase and 25-hydroxycholecalciferol and of plasma parathyroid hormone, intestinal absorption of isotopic calcium and skeletal bone mineral mass as determined by in vivo neutron activation or x-ray photodensitometry. Thirty-nine patients who had been receiving anticonvulsant therapy for an average of 20 years were studied; none had clinical evidence of metabolic bone disease. Decreased serum calcium concentration was noted in 10%, decreased serum phosphorus concentration in 10% and elevated serum alkaline phosphatase concentration in 44%. The mean serum 25-hydroxycholecalciferol concentration was significantly lower (P < 0.001) than in a control group (11.6 v. 19.6 mg/mL). None of 18 patients studied had an increased plasma concentration of parathyroid hormone, and only 1 of 17 patients had decreased intestinal absorption of isotopic calcium. Bone mineral mass was decreased in 44% of 32 patients studied. It was concluded that long-term treatment with anticonvulsant drugs leads to mild abnormalities of calcium metabolism and decreased bone mineral mass in a substantial percentage of adult outpatients with epilepsy. These abnormalities probably predispose the patients to the development of clinically significant metabolic bone disease. PMID:418865

  8. Metabolic Health Status and the Obesity Paradox in Older Adults.

    PubMed

    Cheng, Feon W; Gao, Xiang; Mitchell, Diane C; Wood, Craig; Rolston, David D K; Still, Christopher D; Jensen, Gordon L

    2016-01-01

    The explanation for reduced mortality among older persons with overweight or class I obesity compared to those of desirable weight remains unclear. Our objective was to investigate the joint effects of body mass index (BMI) and metabolic health status on all-cause mortality in a cohort of advanced age. Adults aged 74 ± 4.7 (mean ± SD) years at baseline (n = 4551) were categorized according to BMI (18.5-24.9, 25.0-29.9, 30.0-34.9, and ≥35.0 kg/m(2)) and the presence or absence of a metabolically healthy phenotype (i.e., 0 or 1 risk factors based on a modified Adult Treatment Panel III). Metabolically unhealthy was ≥2 risk factors. There were 2294 deaths over a mean 10.9 years of follow up. Relative to metabolically healthy desirable weight, metabolically healthy overweight or class I obesity was not associated with a greater mortality risk (HR 0.90; 95 CI% 0.73-1.13 and HR 0.58; 95 CI% 0.42-0.80, respectively) (P-interaction <0.001). Results remained consistent in rigorous sensitivity analyses. The "obesity paradox" may be partially explained by the inclusion of metabolically healthy overweight and obese older persons, who do not have elevated mortality risk, in population studies of BMI and mortality. PMID:27559852

  9. [Evaluation of congenital heart disease in adults].

    PubMed

    Oliver Ruiz, José María; Mateos García, Marta; Bret Zurita, Montserrat

    2003-06-01

    Improvements in the diagnosis and surgical treatment of congenital heart disease during infancy and childhood have resulted in an outstanding increase in the prevalence of these entities during adulthood. Congenital heart disease in the adult represents a new diagnostic challenge to the consultant cardiologist, unfamiliar with the anatomical and functional complexities of cardiac malformations. Assessment of adult congenital heart disease with imaging techniques can be as accurate as in children. However, these techniques cannot substitute for a detailed clinical assessment. Physical examination, electrocardiography and chest x-rays remain the three main pillars of bedside diagnosis. Transthoracic echocardiography is undoubtedly the imaging technique which provides most information, and in many situations no additional studies are needed. Nevertheless, ultrasound imaging properties in adults are not as favorable as in children, and prior surgical procedures further impair image quality. Despite recent advances in ultrasound technologies such as harmonic or contrast imaging, other diagnostic procedures are sometimes required. Fortunately, transesophageal echocardiography and magnetic resonance imaging are easily performed in the adult, and do not require anaesthetic support, in contrast to pediatric patients. These techniques, together with nuclear cardiology and cardiac catheterization, complete the second tier of diagnostic techniques for congenital heart disease. To avoid unnecessary repetition of diagnostic procedures, the attending cardiologist should choose the sequence of diagnostic techniques carefully; although the information this yields is often redundant, it is also frequently complementary. This article aims to compare the diagnostic utility of different imaging techniques in adult patients with congenital heart disease, both with and without prior surgical repair.

  10. Salivary Biomarkers in Pediatric Metabolic Disease Research.

    PubMed

    Hartman, Mor-Li; Goodson, J Max; Barake, Roula; Alsmadi, Osama; Al-Mutawa, Sabiha; Ariga, Jitendra; Soparkar, Pramod; Behbehani, Jawad; Behbehani, Kazem

    2016-03-01

    The increasing prevalence of childhood obesity and obesity-related metabolic disorders is now considered a global pandemic. The main goal of the pediatric obesity research community is to identify children who are at risk of becoming obese before their body mass index rises above age norms. To do so, we must identify biomarkers of metabolic health and immunometabolism that can be used for large-scale screening and diagnosis initiatives among at-risk children. Because blood sampling is often unacceptable to both parents and children when there is no direct benefit to the child, as in a community-based research study, there is a clear need for a low-risk, non-invasive sampling strategy. Salivary analysis is now well recognized as a likely candidate for this purpose. In this review, we discuss the physiologic role of saliva and its strengths and limitations as a fluid for biomarker discovery, obesity screening, metabolic disease diagnosis, and response monitoring after interventions. We also describe the current state of the salivary biomarker field as it pertains to metabolic research, with a special emphasis on studies conducted in children and adolescents. Finally, we look forward to technological developments, such as salivary "omics" and point of service diagnostic devices, which have the potential to accelerate the pace of research and discovery in this vitally important field. PMID:27116847

  11. Hyperleptinemia, adiposity, and risk of metabolic syndrome in older adults.

    PubMed

    Mishra, Suruchi; Harris, Tamara B; Hue, Trisha; Miljkovic, Iva; Satterfield, Suzanne; de Rekeneire, Nathalie; Mehta, Mira; Sahyoun, Nadine R

    2013-01-01

    Background. Abdominal adiposity and serum leptin increase with age as does risk of metabolic syndrome. This study investigates the prospective association between leptin and metabolic syndrome risk in relation to adiposity and cytokines. Methods. The Health, Aging, and Body Composition study is a prospective cohort of older adults aged 70 to 79 years. Baseline measurements included leptin, cytokines, BMI, total percent fat, and visceral and subcutaneous fat. Multivariate logistic regression was used to determine the association between leptin and metabolic syndrome (defined per NCEP ATP III) incidence after 6 years of follow-up among 1,120 men and women. Results. Leptin predicted metabolic syndrome in men (P for trend = 0.0002) and women (P for trend = 0.0001). In women, risk of metabolic syndrome increased with higher levels of leptin (compared with quintile 1, quintile 2 RR = 3.29, CI = 1.36, 7.95; quintile 3 RR = 3.25, CI = 1.33, 7.93; quintile 4 RR = 5.21, CI = 2.16, 12.56; and quintile 5 RR = 7.97, CI = 3.30, 19.24) after adjusting for potential confounders. Leptin remained independently associated with metabolic syndrome risk after additional adjustment for adiposity, cytokines, and CRP. Among men, this association was no longer significant after controlling for adiposity. Conclusion. Among older women, elevated concentrations of leptin may increase the risk of metabolic syndrome independent of adiposity and cytokines. PMID:24455217

  12. Hyperleptinemia, Adiposity, and Risk of Metabolic Syndrome in Older Adults

    PubMed Central

    Harris, Tamara B.; Hue, Trisha; Miljkovic, Iva; de Rekeneire, Nathalie; Mehta, Mira; Sahyoun, Nadine R.

    2013-01-01

    Background. Abdominal adiposity and serum leptin increase with age as does risk of metabolic syndrome. This study investigates the prospective association between leptin and metabolic syndrome risk in relation to adiposity and cytokines. Methods. The Health, Aging, and Body Composition study is a prospective cohort of older adults aged 70 to 79 years. Baseline measurements included leptin, cytokines, BMI, total percent fat, and visceral and subcutaneous fat. Multivariate logistic regression was used to determine the association between leptin and metabolic syndrome (defined per NCEP ATP III) incidence after 6 years of follow-up among 1,120 men and women. Results. Leptin predicted metabolic syndrome in men (P for trend = 0.0002) and women (P for trend = 0.0001). In women, risk of metabolic syndrome increased with higher levels of leptin (compared with quintile 1, quintile 2 RR = 3.29, CI = 1.36, 7.95; quintile 3 RR = 3.25, CI = 1.33, 7.93; quintile 4 RR = 5.21, CI = 2.16, 12.56; and quintile 5 RR = 7.97, CI = 3.30, 19.24) after adjusting for potential confounders. Leptin remained independently associated with metabolic syndrome risk after additional adjustment for adiposity, cytokines, and CRP. Among men, this association was no longer significant after controlling for adiposity. Conclusion. Among older women, elevated concentrations of leptin may increase the risk of metabolic syndrome independent of adiposity and cytokines. PMID:24455217

  13. Lipoprotein metabolism in nonalcoholic fatty liver disease

    PubMed Central

    Jiang, Zhenghui Gordon; Robson, Simon C.; Yao, Zemin

    2013-01-01

    Nonalcoholic fatty liver disease (NAFLD), an escalating health problem worldwide, covers a spectrum of pathologies characterized by fatty accumulation in hepatocytes in early stages, with potential progression to liver inflammation, fibrosis, and failure. A close, yet poorly understood link exists between NAFLD and dyslipidemia, a constellation of abnormalities in plasma lipoproteins including triglyceride-rich very low density lipoproteins. Apolipoproteins are a group of primarily liver-derived proteins found in serum lipoproteins; they not only play an extracellular role in lipid transport between vital organs through circulation, but also play an important intracellular role in hepatic lipoprotein assembly and secretion. The liver functions as the central hub for lipoprotein metabolism, as it dictates lipoprotein production and to a significant extent modulates lipoprotein clearance. Lipoprotein metabolism is an integral component of hepatocellular lipid homeostasis and is implicated in the pathogenesis, potential diagnosis, and treatment of NAFLD. PMID:23554788

  14. Improved Cardiovascular Disease Outcomes in Older Adults

    PubMed Central

    Forman, Daniel E.; Alexander, Karen; Brindis, Ralph G.; Curtis, Anne B.; Maurer, Mathew; Rich, Michael W.; Sperling, Laurence; Wenger, Nanette K.

    2016-01-01

    Longevity is increasing and the population of older adults is growing. The biology of aging is conducive to cardiovascular disease (CVD), such that prevalence of coronary artery disease, heart failure, valvular heart disease, arrhythmia and other disorders are increasing as more adults survive into old age.  Furthermore, CVD in older adults is distinctive, with management issues predictably complicated by multimorbidity, polypharmacy, frailty and other complexities of care that increase management risks (e.g., bleeding, falls, and rehospitalization) and uncertainty of outcomes.  In this review, state-of-the-art advances in heart failure, acute coronary syndromes, transcatheter aortic valve replacement, atrial fibrillation, amyloidosis, and CVD prevention are discussed.  Conceptual benefits of treatments are considered in relation to the challenges and ambiguities inherent in their application to older patients. PMID:26918183

  15. Altered Energy Metabolism Pathways in the Posterior Cingulate in Young Adult Apolipoprotein E ɛ4 Carriers

    PubMed Central

    Perkins, Michelle; Wolf, Andrew B.; Chavira, Bernardo; Shonebarger, Daniel; Meckel, J.P.; Leung, Lana; Ballina, Lauren; Ly, Sarah; Saini, Aman; Jones, T. Bucky; Vallejo, Johana; Jentarra, Garilyn; Valla, Jon

    2016-01-01

    The APOE gene, encoding apolipoprotein E, is the primary genetic risk factor for late-onset Alzheimer’s disease (AD). Apolipoprotein E ɛ4 allele (APOE4) carriers have alterations in brain structure and function (as measured by brain imaging) even as young adults. Examination of this population is valuable in further identifying details of these functional changes and their association with vulnerability to AD decades later. Previous work demonstrates functional declines in mitochondrial activity in the posterior cingulate cortex, a key region in the default mode network, which appears to be strongly associated with functional changes relevant to AD risk. Here, we demonstrate alterations in the pathways underlying glucose, ketone, and mitochondrial energy metabolism. Young adult APOE4 carriers displayed upregulation of specific glucose (GLUT1 & GLUT3) and monocarboxylate (MCT2) transporters, the glucose metabolism enzyme hexokinase, the SCOT & AACS enzymes involved in ketone metabolism, and complexes I, II, and IV of the mitochondrial electron transport chain. The monocarboxylate transporter (MCT4) was found to be downregulated in APOE4 carriers. These data suggest that widespread dysregulation of energy metabolism in this at-risk population, even decades before possible disease onset. Therefore, these findings support the idea that alterations in brain energy metabolism may contribute significantly to the risk that APOE4 confers for AD. PMID:27128370

  16. Altered Energy Metabolism Pathways in the Posterior Cingulate in Young Adult Apolipoprotein E ɛ4 Carriers.

    PubMed

    Perkins, Michelle; Wolf, Andrew B; Chavira, Bernardo; Shonebarger, Daniel; Meckel, J P; Leung, Lana; Ballina, Lauren; Ly, Sarah; Saini, Aman; Jones, T Bucky; Vallejo, Johana; Jentarra, Garilyn; Valla, Jon

    2016-04-23

    The APOE gene, encoding apolipoprotein E, is the primary genetic risk factor for late-onset Alzheimer's disease (AD). Apolipoprotein E ɛ4 allele (APOE4) carriers have alterations in brain structure and function (as measured by brain imaging) even as young adults. Examination of this population is valuable in further identifying details of these functional changes and their association with vulnerability to AD decades later. Previous work demonstrates functional declines in mitochondrial activity in the posterior cingulate cortex, a key region in the default mode network, which appears to be strongly associated with functional changes relevant to AD risk. Here, we demonstrate alterations in the pathways underlying glucose, ketone, and mitochondrial energy metabolism. Young adult APOE4 carriers displayed upregulation of specific glucose (GLUT1 & GLUT3) and monocarboxylate (MCT2) transporters, the glucose metabolism enzyme hexokinase, the SCOT & AACS enzymes involved in ketone metabolism, and complexes I, II, and IV of the mitochondrial electron transport chain. The monocarboxylate transporter (MCT4) was found to be downregulated in APOE4 carriers. These data suggest that widespread dysregulation of energy metabolism in this at-risk population, even decades before possible disease onset. Therefore, these findings support the idea that alterations in brain energy metabolism may contribute significantly to the risk that APOE4 confers for AD. PMID:27128370

  17. The metabolic syndrome: a brain disease?

    PubMed

    Buijs, Ruud M; Kreier, Felix

    2006-09-01

    The incidence of obesity with, as consequence, a rise in associated diseases such as diabetes, hypertension and dyslipidemia--the metabolic syndrome--is reaching epidemic proportions in industrialized countries. Here, we provide a hypothesis that the biological clock which normally prepares us each morning for the coming activity period is altered due to a modern life style of low activity during the day and late-night food intake. Furthermore, we review the anatomical evidence supporting the proposal that an unbalanced autonomic nervous system output may lead to the simultaneous occurrence of diabetes type 2, dyslipidemia, hypertension and visceral obesity.

  18. Obesity and Metabolic Disease After Childhood Cancer.

    PubMed

    Barnea, Dana; Raghunathan, Nirupa; Friedman, Danielle Novetsky; Tonorezos, Emily S

    2015-11-01

    As care for the childhood cancer patient has improved significantly, there is an increasing incidence of treatment-related late effects. Obesity and type 2 diabetes mellitus are common and significant metabolic conditions in some populations of adult survivors of childhood cancer. Results from the Childhood Cancer Survivor Study and other large cohorts of childhood cancer survivors reveal that long-term survivors of acute lymphoblastic leukemia and those who received total body irradiation or abdominal radiotherapy are at highest risk. The potential mechanisms for the observed increase in risk, including alterations in leptin and adiponectin, pancreatic insufficiency, poor dietary habits, sedentary lifestyle, and perhaps changes in the composition of the gut microbiota, are reviewed. Discussion of exercise and diet intervention studies shows that further research about the barriers to a healthy lifestyle and other interventions in childhood cancer survivors is warranted.

  19. Vascular and metabolic reserve in Alzheimer's disease.

    PubMed

    Nagata, K; Kondoh, Y; Atchison, R; Sato, M; Satoh, Y; Watahiki, Y; Hirata, Y; Yokoyama, E

    2000-01-01

    Vascular and metabolic reserve were analyzed in probable Alzheimer's disease (AD) and vascular dementia (VaD). Cerebral blood flow (CBF), cerebral blood volume (CBV), cerebral metabolic rate of oxygen (CMRO(2)), and oxygen extraction fraction (OEF) were measured quantitatively with positron emission tomography (PET). Vascular reactivity (VR) was also calculated by comparing the CBF during 5% CO(2) inhalation with the CBF during normal breathing. Vascular transit time (VTT) that was calculated as a ratio of CBV/CBF and VR reflect vasodilating capacity of the small resistance vessels, whereas OEF designates metabolic (oxygen-extraction) reserve in threatening brain ischemia. Significant increase in OEF was seen in the parieto-temporal cortex and both VTT and VR were preserved in AD patients. By constrast, there was no significant increase in OEF whereas VTT was prolonged and VR was markedly depressed in VaD patients. The increase of OEF and preserved VTT and VR seen in AD patients indicate the possible participation of vascular factors in the pathogenesis of AD perhaps at the capillary level.

  20. Metabolic profiling of Alzheimer's disease brains

    NASA Astrophysics Data System (ADS)

    Inoue, Koichi; Tsutsui, Haruhito; Akatsu, Hiroyasu; Hashizume, Yoshio; Matsukawa, Noriyuki; Yamamoto, Takayuki; Toyo'Oka, Toshimasa

    2013-08-01

    Alzheimer's disease (AD) is an irreversible, progressive brain disease and can be definitively diagnosed after death through an examination of senile plaques and neurofibrillary tangles in several brain regions. It is to be expected that changes in the concentration and/or localization of low-molecular-weight molecules are linked to the pathological changes that occur in AD, and determining their identity would provide valuable information regarding AD processes. Here, we propose definitive brain metabolic profiling using ultra-performance liquid chromatography coupled with electrospray time-of-flight mass spectrometry analysis. The acquired data were subjected to principal components analysis to differentiate the frontal and parietal lobes of the AD/Control groups. Significant differences in the levels of spermine and spermidine were identified using S-plot, mass spectra, databases and standards. Based on the investigation of the polyamine metabolite pathway, these data establish that the downstream metabolites of ornithine are increased, potentially implicating ornithine decarboxylase activity in AD pathology.

  1. Sideroblastic anaemia in adult coeliac disease

    PubMed Central

    Dawson, A. M.; Holdsworth, C. D.; Pitcher, C. S.

    1964-01-01

    Anaemia due to pyridoxine deficiency has not previously been described in adult coeliac disease. The patient described here had a sideroblastic bone marrow showing the characteristic perinuclear rings of iron-containing granules and biochemical evidence of pyridoxine deficiency. These changes disappeared completely when the patient was put on a gluten-free diet. ImagesFIG 1 PMID:14209912

  2. Invasive Haemophilus influenzae disease in adults.

    PubMed Central

    Sarangi, J.; Cartwright, K.; Stuart, J.; Brookes, S.; Morris, R.; Slack, M.

    2000-01-01

    We reviewed retrospectively all invasive Haemophilus influenzae (Hi) infections in adults ascertained from reference laboratory records and notifications from five NHS regions over the 5 years from 1 October 1990, a period encompassing the introduction of routine Hib childhood immunization (October 1992). A total of 446 cases were identified, a rate of 0.73 infections per 10(5) adults per annum. Though numbers of Hib infections in adults fell after the introduction of Hib vaccines for children (P = 0.035), and there was no increase in infections caused by other capsulated Hi serotypes, total numbers of invasive Hi infections increased due to a large rise in infections caused by non-capsulated Hi (ncHi) strains (P = 0.0067). There was an unexpectedly low rate of infections in those aged 75 years or more (P < 0.0001). The commonest clinical presentations were pneumonia with bacteraemia (227/350, 65%) and bacteraemia alone (62/350, 18%) and the highest rates of disease were in the 65-74 years age group (P < 0.0001). Clinical presentation was not influenced by the capsulation status of the invading Hi strain. 103/350 cases (29%) died within 1 month, and 207/350 (59%) within 6 months of their Hi infection. Case fatality rates were high in all age groups. Pre-existing diseases were noted in 220/350 cases and were associated with a higher case fatality rate (82% vs. 21%, P < 0.0001). After the introduction of Hib immunization in children, invasive Hib infections in unimmunized adults also declined, but the overall rate of invasive Hi disease in adults increased, with most infections now caused by non-capsulated strains. Physicians and microbiologists should be aware of the changing epidemiology, the high associated mortality and high risk of underlying disease. Invasive haemophilus infections in adults should be investigated and treated aggressively. PMID:10982068

  3. Nutrigenomic programming of cardiovascular and metabolic diseases.

    PubMed

    Ozanne, Susan

    2014-10-01

    Over twenty five years ago epidemiological studies revealed that there was a relationship between patterns of early growth and subsequent risk of diseases such as type 2 diabetes, cardiovascular disease and the metabolic syndrome. Studies of identical twins, individuals who were in utero during periods of famine, discordant siblings and animal models have provided strong evidence that the early environment plays an important role in mediating these relationships. Early nutrition is one such important environmental factor. The concept of early life programming is therefore widely accepted and the underlying mechanisms starting to emerge. These include: (1) Permanent structural changes in an organ due to exposure to suboptimal levels of essential hormones or nutrients during a critical period of development leading to permanent changes in tissue function (2) Persistent epigenetic changes such as DNA methylation and histone modifications and miRNAs leading to changes in gene expression. (3) Permanent effects on regulation of cellular ageing through increases in oxidative stress and mitochondrial dysfunction leading to DNA damage and telomere shortening. Further understanding of these processes will enable the development of preventative and intervention strategies to combat the burden of common diseases such as type 2 diabetes and cardiovascular disease.

  4. Nutrigenomic programming of cardiovascular and metabolic diseases.

    PubMed

    Ozanne, Susan

    2014-10-01

    Over twenty five years ago epidemiological studies revealed that there was a relationship between patterns of early growth and subsequent risk of diseases such as type 2 diabetes, cardiovascular disease and the metabolic syndrome. Studies of identical twins, individuals who were in utero during periods of famine, discordant siblings and animal models have provided strong evidence that the early environment plays an important role in mediating these relationships. Early nutrition is one such important environmental factor. The concept of early life programming is therefore widely accepted and the underlying mechanisms starting to emerge. These include: (1) Permanent structural changes in an organ due to exposure to suboptimal levels of essential hormones or nutrients during a critical period of development leading to permanent changes in tissue function (2) Persistent epigenetic changes such as DNA methylation and histone modifications and miRNAs leading to changes in gene expression. (3) Permanent effects on regulation of cellular ageing through increases in oxidative stress and mitochondrial dysfunction leading to DNA damage and telomere shortening. Further understanding of these processes will enable the development of preventative and intervention strategies to combat the burden of common diseases such as type 2 diabetes and cardiovascular disease. PMID:26461282

  5. Obesity, metabolic health, and mortality in adults: a nationwide population-based study in Korea

    PubMed Central

    Yang, Hae Kyung; Han, Kyungdo; Kwon, Hyuk-Sang; Park, Yong-Moon; Cho, Jae-Hyoung; Yoon, Kun-Ho; Kang, Moo-Il; Cha, Bong-Yun; Lee, Seung-Hwan

    2016-01-01

    BMI, metabolic health status, and their interactions should be considered for estimating mortality risk; however, the data are controversial and unknown in Asians. We aimed to investigate this issue in Korean population. Total 323175 adults were followed-up for 96 (60–120) (median [5–95%]) months in a nationwide population-based cohort study. Participants were classified as “obese” (O) or “non-obese” (NO) using a BMI cut-off of 25 kg/m2. People who developed ≥1 metabolic disease component (hypertension, diabetes, dyslipidaemia) in the index year were considered “metabolically unhealthy” (MU), while those with none were considered “metabolically healthy” (MH). The MUNO group had a significantly higher risk of all-cause (hazard ratio, 1.28 [95% CI, 1.21–1.35]) and cardiovascular (1.88 [1.63–2.16]) mortality, whereas the MHO group had a lower mortality risk (all-cause: 0.81 [0.74–0.88]), cardiovascular: 0.73 [0.57–0.95]), compared to the MHNO group. A similar pattern was noted for cancer and other-cause mortality. Metabolically unhealthy status was associated with higher risk of all-cause and cardiovascular mortality regardless of BMI levels, and there was a dose-response relationship between the number of incident metabolic diseases and mortality risk. In conclusion, poor metabolic health status contributed more to mortality than high BMI did, in Korean adults. PMID:27445194

  6. Dietary Fat Intake and the Risk of Metabolic Syndrome in Korean Adults

    PubMed Central

    Lee, Cheol-Min; Kwon, Hyuk-Tae; Joh, Hee-Kyung; Kim, Young-Ju; Kim, Hyun-Joo; Ahn, Sang-Hyun

    2015-01-01

    Background The effect of dietary fat intake on the risk of cardiovascular disease remains unclear. We investigated the association between dietary fat and specific types of fat intake and the risk of metabolic syndrome. Methods The study population included 1,662 healthy adults who were 50.2 years of age and had no known hypertension, diabetes, hyperlipidemia, or metabolic syndrome at the initial visit. Dietary intake was obtained from a 1-day food record. During 20.7 months of follow-up, we documented 147 cases of metabolic syndrome confirmed by self-report, anthropometric data, and blood test results. The intakes of total fat, vegetable fat, animal fat, saturated fatty acid (SFA), polyunsaturated fatty acid (PUFA), monounsaturated fatty acid (MUFA), and cholesterol level divided by quintile. Multivariate analyses included age, sex, body mass index, smoking status, alcohol intake, physical activity, total calorie, and protein intake. Results Vegetable fat intake was inversely associated with metabolic syndrome risk (odds ratio for the highest vs. the lowest quintile, 0.33; 95% confidence interval, 0.14 to 0.76). Total fat, animal fat, SFA, PUFA, MUFA, and cholesterol intakes showed no association with metabolic syndrome. Vegetable fat intake was inversely associated with the risk of hypertriglyceridemia among the components of metabolic syndrome. Conclusion These data support an inverse association between vegetable fat and the risk of metabolic syndrome. PMID:26435816

  7. Adult Stem Cells and Diseases of Aging

    PubMed Central

    Boyette, Lisa B.; Tuan, Rocky S.

    2014-01-01

    Preservation of adult stem cells pools is critical for maintaining tissue homeostasis into old age. Exhaustion of adult stem cell pools as a result of deranged metabolic signaling, premature senescence as a response to oncogenic insults to the somatic genome, and other causes contribute to tissue degeneration with age. Both progeria, an extreme example of early-onset aging, and heritable longevity have provided avenues to study regulation of the aging program and its impact on adult stem cell compartments. In this review, we discuss recent findings concerning the effects of aging on stem cells, contributions of stem cells to age-related pathologies, examples of signaling pathways at work in these processes, and lessons about cellular aging gleaned from the development and refinement of cellular reprogramming technologies. We highlight emerging therapeutic approaches to manipulation of key signaling pathways corrupting or exhausting adult stem cells, as well as other approaches targeted at maintaining robust stem cell pools to extend not only lifespan but healthspan. PMID:24757526

  8. Pregnancy and adult congenital heart disease.

    PubMed

    Karamermer, Yusuf; Roos-Hesselink, Jolien W

    2007-09-01

    Increasing numbers of women with complex congenital heart disease are reaching childbearing age. Pregnancy is a major issue in the management of adult congenital heart disease. Cardiac disease is one of the most common causes of maternal morbidity and mortality. Complications, such as growth retardation, preterm and premature birth and even fetal and neonatal mortality, are more frequent among children of women with congenital heart disease. The risk of complications is determined by the severity of the cardiac lesion, the presence of cyanosis, the maternal functional class and the use of anticoagulation. However, the pathophysiology of these complications is not completely understood and may be related to a diminished increase in cardiac output and/or endothelial dysfunction. The management of pregnant cardiac patients is based on limited clinical information. This article reviews pre-pregnancy counseling and management during pregnancy in patients with congenital heart disease.

  9. Novel metabolic biomarkers of cardiovascular disease.

    PubMed

    Jensen, Majken K; Bertoia, Monica L; Cahill, Leah E; Agarwal, Isha; Rimm, Eric B; Mukamal, Kenneth J

    2014-11-01

    Coronary heart disease (CHD) accounts for one in every six deaths in US individuals. Great advances have been made in identifying important risk factors for CHD, such as hypertension, diabetes mellitus, smoking and hypercholesterolaemia, which have led to major developments in therapy. In particular, statins represent one of the greatest successes in the prevention of CHD. While these standard risk factors are important, an obvious opportunity exists to take advantage of ongoing scientific research to better risk-stratify individuals and to identify new treatment targets. In this Review, we summarize ongoing scientific research in a number of metabolic molecules or features, including lipoproteins, homocysteine, calcium metabolism and glycaemic markers. We evaluate the current state of the research and the strength of evidence supporting each emerging biomarker. We also discuss whether the associations with CHD are strong and consistent enough to improve current risk stratification metrics, and whether these markers enhance our understanding of the underlying biology of CHD and thus point towards new treatment options.

  10. Childhood obesity affects adult metabolic syndrome and diabetes.

    PubMed

    Liang, Yajun; Hou, Dongqing; Zhao, Xiaoyuan; Wang, Liang; Hu, Yuehua; Liu, Junting; Cheng, Hong; Yang, Ping; Shan, Xinying; Yan, Yinkun; Cruickshank, J Kennedy; Mi, Jie

    2015-09-01

    We seek to observe the association between childhood obesity by different measures and adult obesity, metabolic syndrome (MetS), and diabetes. Thousand two hundred and nine subjects from "Beijing Blood Pressure Cohort Study" were followed 22.9 ± 0.5 years in average from childhood to adulthood. We defined childhood obesity using body mass index (BMI) or left subscapular skinfold (LSSF), and adult obesity as BMI ≥ 28 kg/m(2). MetS was defined according to the joint statement of International Diabetes Federation and American Heart Association with modified waist circumference (≥ 90/85 cm for men/women). Diabetes was defined as fasting plasma glucose ≥ 7.0 mmol/L or blood glucose 2 h after oral glucose tolerance test ≥ 11.1 mmol/L or currently using blood glucose-lowering agents. Multiple linear and logistic regression models were used to assess the association. The incidence of adult obesity was 13.4, 60.0, 48.3, and 65.1 % for children without obesity, having obesity by BMI only, by LSSF only, and by both, respectively. Compared to children without obesity, children obese by LSSF only or by both had higher risk of diabetes. After controlling for adult obesity, childhood obesity predicted independently long-term risks of diabetes (odds ratio 2.8, 95 % confidence interval 1.2-6.3) or abdominal obesity (2.7, 1.6-4.7) other than MetS as a whole (1.2, 0.6-2.4). Childhood obesity predicts long-term risk of adult diabetes, and the effect is independent of adult obesity. LSSF is better than BMI in predicting adult diabetes.

  11. Metabolic syndrome in patients with hematological diseases.

    PubMed

    Annaloro, Claudio; Airaghi, Lorena; Saporiti, Giorgia; Onida, Francesco; Cortelezzi, Agostino; Deliliers, Giorgio Lambertenghi

    2012-08-01

    The term metabolic syndrome (MS) defines a clustering of cardiovascular risk factors, formerly known as syndrome X. There is some debate about the diagnostic criteria; but the most widely accepted framework is that defined by the National Cholesterol Education Program Adult Treatment Panel III, which requires the simultaneous occurrence of at least three of abdominal obesity, arterial hypertension, hyperglycemia, hypertrigliceridemia and low high-density lipoprotein cholesterol (HDL-C). The prevalence of MS increases with age and varies depending on genetic factors. An abnormally high prevalence has been observed in patients with heterogeneous conditions, such as solid organ transplant recipients, AIDS patients and long-term cancer survivors. As some of the pathogenetic factors possibly involved include cyclosporine A, corticosteroids and cancer chemoradiotherapy, it is possible that MS may also be a complication in hematological patients. Some of the characteristics of MS have been reported with a certain frequency in thalassemia patients, and are mainly attributed to iron overload. Impaired hemostasis is a feature of MS rather than a factor predisposing to its development. In oncohematology, an abnormally high prevalence of MS features has been observed in survivors of pediatric acute lymphoblastic leukemia. In addition to corticosteroid- and cancer therapy-related hypogonadism, hypothyroidism and defective growth hormone incretion are other factors related to the development of MS. Moreover, the highest frequency of MS is observed in hematopoietic stem cell transplantation (HSCT) recipients. Pediatric patients and allogeneic HSCT recipients have been the subject of foremost investigations; but adult patients and autologous HSCT recipients have also been studied more recently. A wide range of factors may contribute to the development of MS in HSCT recipients. Unfortunately, the real entity of the problem is far from clear because of the retrospective design of

  12. Microvascular function in younger adults with obesity and metabolic syndrome: role of oxidative stress

    PubMed Central

    Limberg, Jacqueline K.; Harrell, John W.; Johansson, Rebecca E.; Eldridge, Marlowe W.; Proctor, Lester T.; Sebranek, Joshua J.

    2013-01-01

    Older adults with cardiovascular disease exhibit microvascular dysfunction and increased levels of reactive oxygen species (ROS). We hypothesized that microvascular impairments begin early in the disease process and can be improved by scavenging ROS. Forearm blood flow (Doppler ultrasound) was measured in 45 young (32 ± 2 yr old) adults (n = 15/group) classified as lean, obese, and metabolic syndrome (MetSyn). Vasodilation in response to endothelial (ACh) and vascular smooth muscle [nitroprusside (NTP) and epoprostenol (Epo)] agonists was tested before and after intra-arterial infusion of ascorbic acid to scavenge ROS. Vasodilation was assessed as a rise in relative vascular conductance (ml·min−1·dl−1·100 mmHg−1). ACh and NTP responses were preserved (P = 0.825 and P = 0.924, respectively), whereas Epo responses were lower in obese and MetSyn adults (P < 0.05) than in lean controls. Scavenging of ROS via infusion of ascorbic acid resulted in an increase in ACh-mediated (P < 0.001) and NTP-mediated (P < 0.001) relative vascular conductance across all groups, suggesting that oxidative stress influences vascular responsiveness in adults with and without overt cardiovascular disease risk. Ascorbic acid had no effect on Epo-mediated vasodilation (P = 0.267). These results suggest that obese and MetSyn adults exhibit preserved endothelium-dependent vasodilation with reduced dependence on prostacyclin and are consistent with an upregulation of compensatory vascular control mechanisms. PMID:23934859

  13. Hepatosplenic Cat Scratch Disease in Immunocompetent Adults

    PubMed Central

    García, Juan C.; Núñez, Manuel J.; Castro, Begoña; Fernández, Jesús M.; Portillo, Aránzazu; Oteo, José A.

    2014-01-01

    Abstract Cat-scratch disease (CSD) is the most frequent presentation of Bartonella henselae infection. It has a worldwide distribution and is associated with a previous history of scratch or bite from a cat or dog. CSD affects children and teenagers more often (80%) than adults, and it usually has a self-limiting clinical course. Atypical clinical course or systemic symptoms are described in 5%–20% of patients. Among them, hepatosplenic (HS) forms (abscess) have been described. The majority of published cases have affected children or immunosuppressed patients. Few cases of HS forms of CSD in immunocompetent adult hosts have been reported, and data about the management of this condition are scarce. Herein, we present 3 new cases of HS forms of CSD in immunocompetent adults and review 33 other cases retrieved from the literature. We propose an approach to clinical diagnosis and treatment with oral azithromycin. PMID:25398062

  14. Chronic suppurative lung disease in adults

    PubMed Central

    Mangardich, Antranik

    2016-01-01

    Chronic suppurative lung disease (CSLD), characterized by a bronchiectasis-like syndrome in the absence of bronchial dilatation, is well described in the pediatric literature. In some patients, it may be a precursor of bronchiectasis. In adults, this syndrome has not been well described. We present four adult patients without obvious causative exposures who presented with prolonged cough and purulent sputum. Sputum cultures revealed a variety of Gram negative bacteria, fungi and mycobacteria. High resolution CT scanning did not reveal bronchiectasis. Evaluation revealed underlying causes including immunodeficiency in two, and Mycobacterium avium infection. One patient subsequently developed bronchiectasis. All patients improved with therapy. CSLD occurs in adults and has characteristics that distinguish it from typical chronic bronchitis. These include the lack of causative environmental exposures and infection with unusual pathogens. Evaluation and treatment of these patients similar to bronchiectasis patients may lead to clinical improvement. PMID:27747039

  15. Metabolically Healthy Obesity and Its Associates in Mongolian Chinese Adults

    PubMed Central

    Zhang, Mingzhi; Tong, Weijun; Chen, Jing

    2014-01-01

    Abstract Background: Not all obese individuals show cardiometabolic abnormalities. We examined metabolically healthy obesity (MHO) and its associates in 2530 Mongolian Chinese adults. Methods: MHO was defined by waist circumference, low-density lipoprotein (LDL-C) cholesterol, high-density lipoprotein cholesterol (HDL-C), triglycerides (TGs), systolic blood pressure (SBP), diastolic blood pressure (DBP), and glucose. Results: Only 3.0% of the participants had MHO, with 0.8% of men and 4.5% of women having this condition (P<0.001 for sex difference). Despite striking differences in obesity measures, MHO individuals had a comparable cardiometabolic profile to that for metabolically healthy, nonobese individuals (MHNO) and an improved cardiometabolic profile, i.e., lower levels of blood pressure, glucose, insulin, LDL-C, TGs, and higher levels of HDL-C compared to metabolically abnormal individuals (all P<0.01, except for insulin). MHO individuals had lower levels of high-sensitivity C-reactive protein and soluble intercellular adhesion molecule-1, compared to metabolically abnormal individuals, and had comparable levels of these markers to those in MHNO individuals. Furthermore, only 5.3% of MHO individuals had a family history of hypertension, comparable to 5.0% in MHNO individuals, and much lower than 15.9% in metabolically abnormal, nonobese individuals and 12.8% in metabolically abnormal, obese individuals (overall P<0.001). Conclusions: We conclude that MHO is associated with a low inflammation state, and family history of hypertension may play a role in the MHO phenotype. PMID:24460218

  16. Invited review: Opportunities for genetic improvement of metabolic diseases.

    PubMed

    Pryce, J E; Parker Gaddis, K L; Koeck, A; Bastin, C; Abdelsayed, M; Gengler, N; Miglior, F; Heringstad, B; Egger-Danner, C; Stock, K F; Bradley, A J; Cole, J B

    2016-09-01

    Metabolic disorders are disturbances to one or more of the metabolic processes in dairy cattle. Dysfunction of any of these processes is associated with the manifestation of metabolic diseases or disorders. In this review, data recording, incidences, genetic parameters, predictors, and status of genetic evaluations were examined for (1) ketosis, (2) displaced abomasum, (3) milk fever, and (4) tetany, as these are the most prevalent metabolic diseases where published genetic parameters are available. The reported incidences of clinical cases of metabolic disorders are generally low (less than 10% of cows are recorded as having a metabolic disease per herd per year or parity/lactation). Heritability estimates are also low and are typically less than 5%. Genetic correlations between metabolic traits are mainly positive, indicating that selection to improve one of these diseases is likely to have a positive effect on the others. Furthermore, there may also be opportunities to select for general disease resistance in terms of metabolic stability. Although there is inconsistency in published genetic correlation estimates between milk yield and metabolic traits, selection for milk yield may be expected to lead to a deterioration in metabolic disorders. Under-recording and difficulty in diagnosing subclinical cases are among the reasons why interest is growing in using easily measurable predictors of metabolic diseases, either recorded on-farm by using sensors and milk tests or off-farm using data collected from routine milk recording. Some countries have already initiated genetic evaluations of metabolic disease traits and currently most of these use clinical observations of disease. However, there are opportunities to use clinical diseases in addition to predictor traits and genomic information to strengthen genetic evaluations for metabolic health in the future. PMID:27372587

  17. Invited review: Opportunities for genetic improvement of metabolic diseases.

    PubMed

    Pryce, J E; Parker Gaddis, K L; Koeck, A; Bastin, C; Abdelsayed, M; Gengler, N; Miglior, F; Heringstad, B; Egger-Danner, C; Stock, K F; Bradley, A J; Cole, J B

    2016-09-01

    Metabolic disorders are disturbances to one or more of the metabolic processes in dairy cattle. Dysfunction of any of these processes is associated with the manifestation of metabolic diseases or disorders. In this review, data recording, incidences, genetic parameters, predictors, and status of genetic evaluations were examined for (1) ketosis, (2) displaced abomasum, (3) milk fever, and (4) tetany, as these are the most prevalent metabolic diseases where published genetic parameters are available. The reported incidences of clinical cases of metabolic disorders are generally low (less than 10% of cows are recorded as having a metabolic disease per herd per year or parity/lactation). Heritability estimates are also low and are typically less than 5%. Genetic correlations between metabolic traits are mainly positive, indicating that selection to improve one of these diseases is likely to have a positive effect on the others. Furthermore, there may also be opportunities to select for general disease resistance in terms of metabolic stability. Although there is inconsistency in published genetic correlation estimates between milk yield and metabolic traits, selection for milk yield may be expected to lead to a deterioration in metabolic disorders. Under-recording and difficulty in diagnosing subclinical cases are among the reasons why interest is growing in using easily measurable predictors of metabolic diseases, either recorded on-farm by using sensors and milk tests or off-farm using data collected from routine milk recording. Some countries have already initiated genetic evaluations of metabolic disease traits and currently most of these use clinical observations of disease. However, there are opportunities to use clinical diseases in addition to predictor traits and genomic information to strengthen genetic evaluations for metabolic health in the future.

  18. To Test or Not to Test? Metabolic Testing in Adolescents and Adults with Intellectual Disability

    ERIC Educational Resources Information Center

    Moog, Ute; de Die-Smulders, Christine; Martens, Herman; Schrander-Stumpel, Connie; Spaapen, Leo

    2008-01-01

    In order to add to the knowledge on adult phenotypes of metabolic disorders associated with intellectual disability (ID) and to evaluate criteria for recommending metabolic testing of adolescents and adults with unexplained ID, the authors analyzed retrospectively the outcome of metabolic investigations performed during a 10-year period on 256…

  19. The implications of relationships between human diseases and metabolic subpathways.

    PubMed

    Li, Xia; Li, Chunquan; Shang, Desi; Li, Jing; Han, Junwei; Miao, Yingbo; Wang, Yan; Wang, Qianghu; Li, Wei; Wu, Chao; Zhang, Yunpeng; Li, Xiang; Yao, Qianlan

    2011-01-01

    One of the challenging problems in the etiology of diseases is to explore the relationships between initiation and progression of diseases and abnormalities in local regions of metabolic pathways. To gain insight into such relationships, we applied the "k-clique" subpathway identification method to all disease-related gene sets. For each disease, the disease risk regions of metabolic pathways were then identified and considered as subpathways associated with the disease. We finally built a disease-metabolic subpathway network (DMSPN). Through analyses based on network biology, we found that a few subpathways, such as that of cytochrome P450, were highly connected with many diseases, and most belonged to fundamental metabolisms, suggesting that abnormalities of fundamental metabolic processes tend to cause more types of diseases. According to the categories of diseases and subpathways, we tested the clustering phenomenon of diseases and metabolic subpathways in the DMSPN. The results showed that both disease nodes and subpathway nodes displayed slight clustering phenomenon. We also tested correlations between network topology and genes within disease-related metabolic subpathways, and found that within a disease-related subpathway in the DMSPN, the ratio of disease genes and the ratio of tissue-specific genes significantly increased as the number of diseases caused by the subpathway increased. Surprisingly, the ratio of essential genes significantly decreased and the ratio of housekeeping genes remained relatively unchanged. Furthermore, the coexpression levels between disease genes and other types of genes were calculated for each subpathway in the DMSPN. The results indicated that those genes intensely influenced by disease genes, including essential genes and tissue-specific genes, might be significantly associated with the disease diversity of subpathways, suggesting that different kinds of genes within a disease-related subpathway may play significantly

  20. Temperature, hypoxia, and mycobacteriosis: effects on adult striped bass Morone saxatilis metabolic performance.

    PubMed

    Lapointe, Dominique; Vogelbein, Wolfgang K; Fabrizio, Mary C; Gauthier, David T; Brill, Richard W

    2014-02-19

    Mycobacteriosis, a chronic bacterial disease of fishes, is prevalent in adult striped bass from Chesapeake Bay (USA). Although environmental factors may play a role in disease expression, the interaction between the disease and environmental stress remains unexplored. We therefore examined the individual and interactive effects of elevated temperature, hypoxia, and mycobacteriosis on the metabolism of wild-caught adult striped bass from Chesapeake Bay using respirometry. Because the spleen is the primary target organ of mycobacteriosis in striped bass, we hypothesized that the disease interferes with the ability of fish to increase their hematocrit in the face of increasing oxygen demands. We determined standard metabolic rate (SMR), maximum metabolic rate under normoxia (MMRN), critical oxygen saturation (S(crit)), and MMR under hypoxia (3 mg O(2) l-1: MMR(H)) for healthy and visibly diseased fish (i.e. exhibiting skin lesions indicative of mycobacteriosis). Measurements were taken at a temperature within the preferred thermal range (20°C) and at an elevated temperature (28°C) considered stressful to striped bass. In addition, we calculated aerobic scope (AS(N) = MMR(N) - SMR, AS(H) = MMR(H) - SMR) and factorial scope (FS(N) = MMR(N) SMR-1, FS(H) = MMR(H) SMR-1). SMR increased with increasing temperature, and hypoxia reduced MMR, AS, and FS. Mycobacteriosis alone did not affect either MMR(N) or MMR(H). However, elevated temperature affected the ability of diseased striped bass to tolerate hypoxia (S(crit)). Overall, our data indicate that striped bass performance under hypoxia is impaired, and that elevated water temperatures, hypoxia, and severe mycobacteriosis together reduce aerobic scope more than any of these stressors acting alone. We conclude that the scope for activity of diseased striped bass in warm hypoxic waters is significantly compromised. PMID:24553417

  1. Temperature, hypoxia, and mycobacteriosis: effects on adult striped bass Morone saxatilis metabolic performance.

    PubMed

    Lapointe, Dominique; Vogelbein, Wolfgang K; Fabrizio, Mary C; Gauthier, David T; Brill, Richard W

    2014-02-19

    Mycobacteriosis, a chronic bacterial disease of fishes, is prevalent in adult striped bass from Chesapeake Bay (USA). Although environmental factors may play a role in disease expression, the interaction between the disease and environmental stress remains unexplored. We therefore examined the individual and interactive effects of elevated temperature, hypoxia, and mycobacteriosis on the metabolism of wild-caught adult striped bass from Chesapeake Bay using respirometry. Because the spleen is the primary target organ of mycobacteriosis in striped bass, we hypothesized that the disease interferes with the ability of fish to increase their hematocrit in the face of increasing oxygen demands. We determined standard metabolic rate (SMR), maximum metabolic rate under normoxia (MMRN), critical oxygen saturation (S(crit)), and MMR under hypoxia (3 mg O(2) l-1: MMR(H)) for healthy and visibly diseased fish (i.e. exhibiting skin lesions indicative of mycobacteriosis). Measurements were taken at a temperature within the preferred thermal range (20°C) and at an elevated temperature (28°C) considered stressful to striped bass. In addition, we calculated aerobic scope (AS(N) = MMR(N) - SMR, AS(H) = MMR(H) - SMR) and factorial scope (FS(N) = MMR(N) SMR-1, FS(H) = MMR(H) SMR-1). SMR increased with increasing temperature, and hypoxia reduced MMR, AS, and FS. Mycobacteriosis alone did not affect either MMR(N) or MMR(H). However, elevated temperature affected the ability of diseased striped bass to tolerate hypoxia (S(crit)). Overall, our data indicate that striped bass performance under hypoxia is impaired, and that elevated water temperatures, hypoxia, and severe mycobacteriosis together reduce aerobic scope more than any of these stressors acting alone. We conclude that the scope for activity of diseased striped bass in warm hypoxic waters is significantly compromised.

  2. [Approach to congenital heart disease in adults].

    PubMed

    Alva Espinosa, Carlos

    2006-01-01

    After a few decades treating patients with congenital heart disease during childhood, we now face the problem of dealing with many of them as adults and few cases with disorders detected in adult life. The number of patients, with and without surgery is growing up rapidly. Conservatively speaking, there are in Mexico approximately 300 thousands patients with this condition, increasing by 15 thousands patients per year. In addition to the complexity of the congenital pathology, the knowledge of acquired diseases should be incorporated as well as the genetic advise, pregnancy care and specialized psychological support. The approach to these patients begins with stratification; diagnosis and treatment requiring a multidisciplinary, well informed and an capable to perform together medical team.

  3. Deregulation of sphingolipid metabolism in Alzheimer's disease

    PubMed Central

    He, Xingxuan; Huang, Yu; Li, Bin; Gong, Cheng-Xing; Schuchman, Edward H.

    2010-01-01

    Abnormal sphingolipid metabolism has been previously reported in Alzheimer's disease (AD). To extend these findings, several sphingolipids and sphingolipid hydrolases were analyzed in brain samples from AD patients and age-matched normal individuals. We found a pattern of elevated acid sphingomyelinase (ASM) and acid ceramidase (AC) expression in AD, leading to a reduction in sphingomyelin and elevation of ceramide. More sphingosine also was found in the AD brains, although sphingosine-1-phosphate (S1P) levels were reduced. Notably, significant correlations were observed between the brain ASM and S1P levels and the levels of amyloid beta peptide (Aβ) and phosphorylated tau protein. Based on these findings, neuronal cell cultures were treated with Aβ oligomers, which were found to activate ASM, increase ceramide, and induce apoptosis. Pre-treatment of the neurons with purified, recombinant AC prevented the cells from undergoing Aβ-induced apoptosis. We propose that ASM activation is an important pathological event leading to AD, perhaps due to Aβ deposition. The downstream consequences of ASM activation are elevated ceramide, activation of ceramidases, and production of sphingosine. The reduced levels of S1P in the AD brain, together with elevated ceramide, likely contribute to the disease pathogenesis. PMID:18547682

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

    ClinicalTrials.gov

    2016-07-27

    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

  5. Inherited metabolic diseases affecting the carrier.

    PubMed

    Endres, W

    1997-03-01

    The objective of this review is to draw attention to those inherited metabolic traits which are potentially harmful also for the carrier, and to outline preventive measures, at least for obligate heterozygotes, i.e. parents of homozygous children. Concerning carriers of food-dependent abnormalities, early vascular disease in homocystinuria, hyperammonaemic episodes in ornithine transcarbamylase deficiency, presenile cataracts in galactosaemia as well as galactokinase deficiency, spastic paraparesis in X-linked adrenoleukodystrophy, and HELLP syndrome in mothers of babies with long-chain 3-hydroxyacyl-coenzyme A dehydrogenase deficiency have to be mentioned. In the group of food-independent disorders, clinical features in carriers may be paraesthesias and corneal dystrophy in Fabry disease, lens clouding in Lowe syndrome, lung and/or liver diseases in alpha 1-antitrypsin deficiency, and renal stones in cystinuria type II and III. Finally, two monogenic carrier states are known which in pregnant individuals could possibly afflict the developing fetus, i.e. heterozygosity for galactosaemia and for phenylketonuria. Elevated levels of galactose-1-phosphate have been found in red blood cells of infants heterozygous for galactosaemia born to heterozygous mothers. Aspartame in very high doses is reported to increase blood phenylalanine levels in heterozygotes for phenylketonuria, thus being a risk for the fetus of a heterozygous mother. For some of these carrier states preventive measures can be recommended, e.g. restriction of lactose in parents and heterozygous grandparents of children with galactosaemia and galactokinase deficiency as well as transiently in infants heterozygous for galactosaemia, dietary supplementation with monounsaturated fatty acids in symptomatic carriers for X-linked adrenoleukodystrophy, avoidance of smoking and alcohol in heterozygotes for alpha 1-antitrypsin deficiency, avoidance of episodes of dehydration in heterozygotes for cystinuria, and

  6. Periodontal disease: the influence of metabolic syndrome

    PubMed Central

    2012-01-01

    Metabolic syndrome (MetS) is a cluster of cardiovascular risk factors that include obesity, impaired glucose tolerance or diabetes, hyperinsulinemia, hypertension, and dyslipidemia. Recently, more attention has been reserved to the correlation between periodontitis and systemic health. MetS is characterized by oxidative stress, a condition in which the equilibrium between the production and the inactivation of reactive oxygen species (ROS) becomes disrupted. ROS have an essential role in a variety of physiological systems, but under a condition of oxidative stress, they contribute to cellular dysfunction and damage. Oxidative stress may act as a common link to explain the relationship between each component of MetS and periodontitis. All those conditions show increased serum levels of products derived from oxidative damage, promoting a proinflammatory state. Moreover, adipocytokines, produced by the fat cells of fat tissue, might modulate the balance between oxidant and antioxidant activities. An increased caloric intake involves a higher metabolic activity, which results in an increased production of ROS, inducing insulin resistance. At the same time, obese patients require more insulin to maintain blood glucose homeostasis – a state known as hyperinsulinemia, a condition that can evolve into type 2 diabetes. Oxidation products can increase neutrophil adhesion and chemotaxis, thus favoring oxidative damage. Hyperglycemia and an oxidizing state promote the genesis of advanced glycation end-products, which could also be implicated in the degeneration and damage of periodontal tissue. Thus, MetS, the whole of interconnected factors, presents systemic and local manifestations, such as cardiovascular disease and periodontitis, related by a common factor known as oxidative stress. PMID:23009606

  7. Adult Celiac Disease and Its Malignant Complications

    PubMed Central

    2009-01-01

    Adult celiac disease is a chronic intestinal disorder that has been estimated to affect up to 1-2% of the population in some nations. Awareness of the disease has increased, but still it remains markedly underdiagnosed. Celiac disease is a pathologically defined condition with several characteristic clinical scenarios that should lead the clinician to suspect its presence. Critical to diagnosis is a documented responsiveness to a gluten-free diet. After diagnosis and treatment, symptoms and biopsy-proven changes may recur and appear refractory to a gluten-free diet. Recurrent symptoms are most often due to poor diet compliance, a ubiquitous and unrecognized gluten source, an initially incorrect diagnosis, or an associated disease or complication of celiac disease. Some patients with persistent symptoms and biopsy-proven changes may not have celiac disease at all, instead suffering from a sprue-like intestinal disease, so-called unclassified sprue, which is a specific entity that does not appear to respond to a gluten-free diet. Some of these patients eventually prove to have an underlying malignant cause, particularly lymphoma. The risk of developing lymphoma and other malignancies is increased in celiac disease, especially if initially diagnosed in the elderly, or late in the clinical course of the disease. However, recent studies suggest that the risk of gastric and colon cancer is low. This has led to the hypothesis that untreated celiac disease may be protective, possibly due to impaired absorption and more rapid excretion of fat or fat-soluble agents, including hydrocarbons and other putative cocarcinogens, which are implicated in the pathogenesis of colorectal cancer. PMID:20431755

  8. [Impact of metabolic syndrome on chronic kidney disease].

    PubMed

    Calò, L A

    2006-12-01

    Metabolic syndrome has been recognized as possible risk factor for renal damage and the increased prevalence of both metabolic syndrome and renal disease justifies the increasing interest of the nephrology community toward the metabolic syndrome as another possible inducing cause of chronic renal disease, although the available evidence about a direct causal relationship between metabolic syndrome and development of renal disease so far is scanty. The not easy separation of the negative effects on renal function of metabolic syndrome from those derived from hypertension and diabetes per se, however, does not reduce the interest toward a possible direct impact of metabolic syndrome on renal disease. This also in consideration that other important factors linked with metabolic syndrome, such as for example obesity, have direct independent impact on the development of abnormalities such as microalbuminuria and or overt renal disease. Planning of clinical trials specifically for patients with metabolic syndrome could be helpful to give definitive answers on a possible direct impact of metabolic syndrome on chronic renal disease.

  9. Hepatocyte transplantation for inherited metabolic diseases of the liver.

    PubMed

    Jorns, C; Ellis, E C; Nowak, G; Fischler, B; Nemeth, A; Strom, S C; Ericzon, B G

    2012-09-01

    Inherited metabolic diseases of the liver are characterized by deficiency of a hepatic enzyme or protein often resulting in life-threatening disease. The remaining liver function is usually normal. For most patients, treatment consists of supportive therapy, and the only curative option is liver transplantation. Hepatocyte transplantation is a promising therapy for patients with inherited metabolic liver diseases, which offers a less invasive and fully reversible approach. Procedure-related complications are rare. Here, we review the experience of hepatocyte transplantation for metabolic liver diseases and discuss the major obstacles that need to be overcome to establish hepatocyte transplantation as a reliable treatment option in the clinic.

  10. Pediatric liver transplantation in metabolic disease: clinical decision making.

    PubMed

    Shneider, Benjamin L

    2002-02-01

    Proper utilization of liver transplantation in the management of pediatric metabolic diseases requires a comprehensive understanding of both metabolic disease and the risk and benefits of transplantation. This brief review focuses on issues that pertain to the treatment of tyrosinemia type I, bile acid biosynthesis disorders, primary hyperoxaluria, Crigler-Najjar Type I, and mitochondrial diseases. These entities are used as prototypes to illustrate many of the principles that are applied in a more general sense to the management of metabolic diseases. The natural history of these disorders are considered in the context of the risks of liver transplantation. Indications, contraindications, and both current and future alternatives to transplantation, are considered.

  11. Metabolic Effects of Social Isolation in Adult C57BL/6 Mice

    PubMed Central

    Sun, Meng; Choi, Eugene Y.; Magee, Daniel J.; Stets, Colin W.; During, Matthew J.; Lin, En-Ju D.

    2014-01-01

    Obesity and metabolic dysfunction are risk factors for a number of chronic diseases, such as type 2 diabetes, hypertension, heart disease, stroke, and certain forms of cancers. Both animal studies and human population-based and clinical studies have suggested that chronic stress is a risk factor for metabolic disorders. A good social support system is known to exert positive effects on the mental and physical well-being of an individual. On the other hand, long-term deprivation of social contacts may represent a stressful condition that has negative effects on health. In the present study, we investigated the effects of chronic social isolation on metabolic parameters in adult C57BL/6 mice. We found that individually housed mice had increased adipose mass compared to group-housed mice, despite comparable body weight. The mechanism for the expansion of white adipose tissue mass was depot-specific. Notably, food intake was reduced in the social isolated animals, which occurred around the light-dark phase transition periods. Similarly, reductions in heat generated and the respiratory exchange ratio were observed during the light-dark transitions. These phase-specific changes due to long-term social isolation have not been reported previously. Our study shows social isolation contributes to increased adiposity and altered metabolic functions. PMID:27433503

  12. Protein and leucine metabolism in maple syrup urine disease

    SciTech Connect

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

    1990-04-01

    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.

  13. RNA metabolism in the pathogenesis of Parkinson׳s disease.

    PubMed

    Lu, Bingwei; Gehrke, Stephan; Wu, Zhihao

    2014-10-10

    Neurodegenerative diseases such as Parkinson׳s disease are progressive disorders of the nervous system that affect the function and maintenance of specific neuronal populations. While most disease cases are sporadic with no known cause, a small percentage of disease cases are caused by inherited genetic mutations. The identification of genes associated with the familial forms of the diseases and subsequent studies of proteins encoded by the disease genes in cellular or animal models have offered much-needed insights into the molecular and cellular mechanisms underlying disease pathogenesis. Recent studies of the familial Parkinson׳s disease genes have emphasized the importance of RNA metabolism, particularly mRNA translation, in the disease process. It is anticipated that continued studies on the role of RNA metabolism in Parkinson׳s disease will offer unifying mechanisms for understanding the cause of neuronal dysfunction and degeneration and facilitate the development of novel and rational strategies for treating this debilitating disease.

  14. Metabolic diseases and pro- and prebiotics: Mechanistic insights

    PubMed Central

    2012-01-01

    Metabolic diseases, such as obesity and type 2 diabetes, are world-wide health problems. The prevalence of metabolic diseases is associated with dynamic changes in dietary macronutrient intake during the past decades. Based on national statistics and from a public health viewpoint, traditional approaches, such as diet and physical activity, have been unsuccessful in decreasing the prevalence of metabolic diseases. Since the approaches strongly rely on individual’s behavior and motivation, novel science-based strategies should be considered for prevention and therapy for the diseases. Metabolism and immune system are linked. Both overnutrition and infection result in inflammation through nutrient and pathogen sensing systems which recognize compounds with structural similarities. Dietary macronutrients (fats and sugars) can induce inflammation through activation of an innate immune receptor, Toll-like receptor 4 (TLR4). Long-term intake of diets high in fats and meats appear to induce chronic systemic low-grade inflammation, endotoxicity, and metabolic diseases. Recent investigations support the idea of the involvement of intestinal bacteria in host metabolism and preventative and therapeutic potentials of probiotic and prebiotic interventions for metabolic diseases. Specific intestinal bacteria seem to serve as lipopolysaccharide (LPS) sources through LPS and/or bacterial translocation into the circulation due to a vulnerable microbial barrier and increased intestinal permeability and to play a role in systemic inflammation and progression of metabolic diseases. This review focuses on mechanistic links between metabolic diseases (mainly obesity and type 2 diabetes), chronic systemic low-grade inflammation, intestinal environment, and nutrition and prospective views of probiotic and prebiotic interventions for the diseases. PMID:22713169

  15. Metabolic syndrome and chronic kidney disease.

    PubMed

    Belarbia, Anis; Nouira, Safa; Sahtout, Wissal; Guedri, Yosra; Achour, Abdellatif

    2015-09-01

    To determine the prevalence of metabolic syndrome (MS) in chronic kidney disease (CKD) patients as well as its effects on the progression of CKD, we conducted a prospective, longitudinal study including 180 patients with chronic renal failure followed at the outpatient service of Nephrology at the Saloul's University Hospital of Sousse (Tunisia) over six months. Our study population consisted of 101 men and 79 women. Chronic glomerulonephritis (36.6%) was the most frequent nephropathy. The mean serum creatinine was 249 ± 200 mmol/L and the mean estimated glomerular filtration rate (eGFR) was 55.8 ± 49.2 mL/min. Cardiovascular (CV) impairment was found in 27.2% of the patients. The prevalence of MS was 42.2%. Women had significantly more abdominal obesity than men. Subjects with MS were significantly older and predominantly females who had higher blood pressure and body mass index (BMI). CV complications were more frequent among the MS subjects than among the controls. Glycemia, triglycerides, total cholesterol and low-density lipoprotein-cholesterol (LDL-c) were significantly higher in the group of CKD patients with MS. However, the occurrence of MS was not influenced by the nature of nephropathy, the degree of the CKD and the use of renin-angiotensin blockers or statins. In multivariate analysis, predictors of occurrence of MS in our series included older age, female gender and higher BMI and LDL-c levels. The prevalence of MS in patients with CKD is higher than the general population. These patients should receive special multidisciplinary care to limit CV complications.

  16. Metabolic Equivalent in Adolescents, Active Adults and Pregnant Women.

    PubMed

    Melzer, Katarina; Heydenreich, Juliane; Schutz, Yves; Renaud, Anne; Kayser, Bengt; Mäder, Urs

    2016-01-01

    "Metabolic Equivalent" (MET) represents a standard amount of oxygen consumed by the body under resting conditions, and is defined as 3.5 mL O₂/kg × min or ~1 kcal/kg × h. It is used to express the energy cost of physical activity in multiples of MET. However, universal application of the 1-MET standard was questioned in previous studies, because it does not apply well to all individuals. Height, weight and resting metabolic rate (RMR, measured by indirect calorimetry) were measured in adolescent males (n = 50) and females (n = 50), women during pregnancy (gestation week 35-41, n = 46), women 24-53 weeks postpartum (n = 27), and active men (n = 30), and were compared to values predicted by the 1-MET standard. The RMR of adolescent males (1.28 kcal/kg × h) was significantly higher than that of adolescent females (1.11 kcal/kg × h), with or without the effects of puberty stage and physical activity levels. The RMR of the pregnant and post-pregnant subjects were not significantly different. The RMR of the active normal weight (0.92 kcal/kg × h) and overweight (0.89 kcal/kg × h) adult males were significantly lower than the 1-MET value. It follows that the 1-MET standard is inadequate for use not only in adult men and women, but also in adolescents and physically active men. It is therefore recommended that practitioners estimate RMR with equations taking into account individual characteristics, such as sex, age and Body Mass Index, and not rely on the 1-MET standard. PMID:27447667

  17. Metabolic Equivalent in Adolescents, Active Adults and Pregnant Women

    PubMed Central

    Melzer, Katarina; Heydenreich, Juliane; Schutz, Yves; Renaud, Anne; Kayser, Bengt; Mäder, Urs

    2016-01-01

    Metabolic Equivalent” (MET) represents a standard amount of oxygen consumed by the body under resting conditions, and is defined as 3.5 mL O2/kg × min or ~1 kcal/kg × h. It is used to express the energy cost of physical activity in multiples of MET. However, universal application of the 1-MET standard was questioned in previous studies, because it does not apply well to all individuals. Height, weight and resting metabolic rate (RMR, measured by indirect calorimetry) were measured in adolescent males (n = 50) and females (n = 50), women during pregnancy (gestation week 35–41, n = 46), women 24–53 weeks postpartum (n = 27), and active men (n = 30), and were compared to values predicted by the 1-MET standard. The RMR of adolescent males (1.28 kcal/kg × h) was significantly higher than that of adolescent females (1.11 kcal/kg × h), with or without the effects of puberty stage and physical activity levels. The RMR of the pregnant and post-pregnant subjects were not significantly different. The RMR of the active normal weight (0.92 kcal/kg × h) and overweight (0.89 kcal/kg × h) adult males were significantly lower than the 1-MET value. It follows that the 1-MET standard is inadequate for use not only in adult men and women, but also in adolescents and physically active men. It is therefore recommended that practitioners estimate RMR with equations taking into account individual characteristics, such as sex, age and Body Mass Index, and not rely on the 1-MET standard. PMID:27447667

  18. Metabolic Syndrome As an Underlying Disease Entity and Its Relationship to Subclinical Atherosclerosis in Andean Hispanics

    PubMed Central

    Medina-Lezama, Josefina; Arguelles, William; Goldberg, Ronald; Schneiderman, Neil; Khan, Zubair; Morey, Oscar O.; Raja, Muhammad Waheed; Paz, Roberto; Chirinos, Julio A.; Llabre, Maria M.

    2014-01-01

    Abstract Background: The question of whether the metabolic syndrome truly reflects a single disease entity with a common underlying pathology remains unclear. In this study, we assess whether metabolic syndrome represents an underlying disease construct in a large population-based sample of Andean Hispanic adults and examine its relationship to subclinical atherosclerosis. Methods: The study sample was comprised of 2513 participants. Confirmatory factor analysis (CFA) was used to identify a metabolic syndrome latent factor using waist circumference, systolic and diastolic blood pressure, high-density lipoprotein cholesterol (HDL-C), triglycerides (TGs), and glucose levels as indicators. The relationship with subclinical atherosclerosis, measured by carotid intima media thickness (cIMT), was assessed using structural equation modeling. Results: Results supported the proposed structure of the metabolic syndrome latent factor evidenced by adequate fit indexes. HDL-C did not significantly load on the metabolic syndrome latent factor (standardized factor loading=0.01, P=0.88). The metabolic syndrome latent factor was significantly associated with cIMT in women (B=0.007, P<0.001) and men (B=0.008, P<0.001) after controlling for age, low-density lipoprotein cholesterol and smoking. Conclusions: Our findings suggest that metabolic syndrome components, such as waist circumference, blood pressure, TGs, and glucose levels, but not HDL-C, share a common underlying pathophysiology that may contribute to the progression of atherosclerosis in Andean Hispanics. Its longitudinal association with cardiovascular disease should be the focus of future research. PMID:24206171

  19. Cancer as a metabolic disease: implications for novel therapeutics.

    PubMed

    Seyfried, Thomas N; Flores, Roberto E; Poff, Angela M; D'Agostino, Dominic P

    2014-03-01

    Emerging evidence indicates that cancer is primarily a metabolic disease involving disturbances in energy production through respiration and fermentation. The genomic instability observed in tumor cells and all other recognized hallmarks of cancer are considered downstream epiphenomena of the initial disturbance of cellular energy metabolism. The disturbances in tumor cell energy metabolism can be linked to abnormalities in the structure and function of the mitochondria. When viewed as a mitochondrial metabolic disease, the evolutionary theory of Lamarck can better explain cancer progression than can the evolutionary theory of Darwin. Cancer growth and progression can be managed following a whole body transition from fermentable metabolites, primarily glucose and glutamine, to respiratory metabolites, primarily ketone bodies. As each individual is a unique metabolic entity, personalization of metabolic therapy as a broad-based cancer treatment strategy will require fine-tuning to match the therapy to an individual's unique physiology.

  20. Cancer as a metabolic disease: implications for novel therapeutics.

    PubMed

    Seyfried, Thomas N; Flores, Roberto E; Poff, Angela M; D'Agostino, Dominic P

    2014-03-01

    Emerging evidence indicates that cancer is primarily a metabolic disease involving disturbances in energy production through respiration and fermentation. The genomic instability observed in tumor cells and all other recognized hallmarks of cancer are considered downstream epiphenomena of the initial disturbance of cellular energy metabolism. The disturbances in tumor cell energy metabolism can be linked to abnormalities in the structure and function of the mitochondria. When viewed as a mitochondrial metabolic disease, the evolutionary theory of Lamarck can better explain cancer progression than can the evolutionary theory of Darwin. Cancer growth and progression can be managed following a whole body transition from fermentable metabolites, primarily glucose and glutamine, to respiratory metabolites, primarily ketone bodies. As each individual is a unique metabolic entity, personalization of metabolic therapy as a broad-based cancer treatment strategy will require fine-tuning to match the therapy to an individual's unique physiology. PMID:24343361

  1. Maternal protein restriction impairs the transcriptional metabolic flexibility of skeletal muscle in adult rat offspring.

    PubMed

    da Silva Aragão, Raquel; Guzmán-Quevedo, Omar; Pérez-García, Georgina; Manhães-de-Castro, Raul; Bolaños-Jiménez, Francisco

    2014-08-14

    Skeletal muscle exhibits a remarkable flexibility in the usage of fuel in response to the nutrient intake and energy demands of the organism. In fact, increased physical activity and fasting trigger a transcriptional programme in skeletal muscle cells leading to a switch from carbohydrate to lipid oxidation. Impaired metabolic flexibility has been reported to be associated with obesity and type 2 diabetes, but it is not known whether the disability to adapt to metabolic demands is a cause or a consequence of these pathological conditions. Inasmuch as a poor nutritional environment during early life is a predisposing factor for the development of metabolic diseases in adulthood, in the present study, we aimed to determine the long-term effects of maternal malnutrition on the metabolic flexibility of offspring skeletal muscle. To this end, the transcriptional responses of the soleus and extensor digitorum longus muscles to fasting were evaluated in adult rats born to dams fed a control (17 % protein) or a low-protein (8 % protein, protein restricted (PR)) diet throughout pregnancy and lactation. With the exception of reduced body weight and reduced plasma concentrations of TAG, PR rats exhibited a metabolic profile that was the same as that of the control rats. In the fed state, PR rats exhibited an enhanced expression of key regulatory genes of fatty acid oxidation including CPT1a, PGC-1α, UCP3 and PPARα and an impaired expression of genes that increase the capacity for fat oxidation in response to fasting. These results suggest that impaired metabolic inflexibility precedes and may contribute to the development of metabolic disorders associated with early malnutrition. PMID:24823946

  2. [Relationship between metabolic syndrome and urinary stone disease].

    PubMed

    Yamaguchi, Satoshi

    2011-10-01

    Epidemiologically, there are many same characteristics among patients with urolithiasis, life-style related diseases and metabolic syndrome. In a comparison with the major urological diseases, the patients with stone disease have the largest amount of visceral fat on computerized tomography. The patients who finally had a diagnosis of metabolic syndrome in urolithiasis were 43% of men and female 31%. The clinical features of the patients include increased urinary oxalate excretion, abnormal uric acid metabolism, and acidic urine. The basic studies by the animal experiments suggest that there is a close relationship between urolithiasis and metabolic syndrome. After the treatment of the urinary stone, it is very important to make a long-term follow-up by not only the prevention of recurrent stone episode but also life style management and medical treatment for metabolic syndrome. PMID:21960234

  3. Recent developments in metabolic bone diseases: a gnathic perspective.

    PubMed

    Raubenheimer, Erich J; Noffke, Claudia E; Hendrik, Hilde D

    2014-12-01

    Metabolic bone diseases often are asymptomatic and progress sub clinically. Many patients present at a late stage with catastrophic skeletal and extra skeletal complications. In this article, we provide an overview of normal bone remodeling and a synopsis of recent developments in the following conditions: osteoporosis, rickets/osteomalacia, endocrine-induced bone disease, chronic kidney disease-mineral bone disorder and Paget's disease of bone. Our discussion will emphasize the clinical and microscopic manifestations of these diseases in the jaws.

  4. Dietary factors associated with metabolic syndrome in Brazilian adults

    PubMed Central

    2012-01-01

    Background Metabolic Syndrome (MS) is defined as the association of numerous factors that increase cardiovascular risk and diet is one of the main factors related to increase the MS in the population. This study aimed to evaluate the association of diet on the presence of MS in an adult population sample. Methodology 305 adults were clinically screened to participate in a lifestyle modification program. Anthropometric assessments included waist circumference (WC), body fat and calculated BMI (kg/m2) and muscle-mass index (MMI kg/m2). Dietary intake was estimated by 24 h dietary recall. Fasting blood was used for biochemical analysis. MS was diagnosed using NCEP-ATPIII (2001) criteria with adaptation for glucose (≥ 100 mg/dL). Logistic regression (Odds ratio) was performed in order to determine the odds ratio for developing MS according to dietary intake. Results An adequate intake of fruits, OR = 0.52 (CI:0.28-0.98), and an intake of more than 8 different items in the diet (variety), OR = 0.31 (CI:0.12-0.79) showed to be a protective factor against a diagnosis of MS. Saturated fat intake greater than 10% of total caloric value represented a risk for MS diagnosis, OR = 2.0 (1.04-3.84). Conclusion Regarding the dietary aspect, a risk factor for MS was higher intake of saturated fat, and protective factors were high diet variety and adequate fruit intake. PMID:22417631

  5. Secondary muscle pathology and metabolic dysregulation in adults with cerebral palsy

    PubMed Central

    Gordon, Paul M.; Hurvitz, Edward A.; Burant, Charles F.

    2012-01-01

    Cerebral palsy (CP) is caused by an insult to or malformation of the developing brain which affects motor control centers and causes alterations in growth, development, and overall health throughout the life span. In addition to the disruption in development caused by the primary neurological insult, CP is associated with exaggerated sedentary behaviors and a hallmark accelerated progression of muscle pathology compared with typically developing children and adults. Factors such as excess adipose tissue deposition and altered partitioning, insulin resistance, and chronic inflammation may increase the severity of muscle pathology throughout adulthood and lead to cardiometabolic disease risk and/or early mortality. We describe a model of exaggerated health risk represented in adults with CP and discuss the mechanisms and secondary consequences associated with chronic sedentary behavior, obesity, aging, and muscle spasticity. Moreover, we highlight novel evidence that implicates aberrant inflammation in CP as a potential mechanism linking both metabolic and cognitive dysregulation in a cyclical pattern. PMID:22912367

  6. Fatty acid metabolism: Implications for diet, genetic variation, and disease

    PubMed Central

    Suburu, Janel; Gu, Zhennan; Chen, Haiqin; Chen, Wei; Zhang, Hao; Chen, Yong Q.

    2014-01-01

    Cultures across the globe, especially Western societies, are burdened by chronic diseases such as obesity, metabolic syndrome, cardiovascular disease, and cancer. Several factors, including diet, genetics, and sedentary lifestyle, are suspected culprits to the development and progression of these health maladies. Fatty acids are primary constituents of cellular physiology. Humans can acquire fatty acids by de novo synthesis from carbohydrate or protein sources or by dietary consumption. Importantly, regulation of their metabolism is critical to sustain balanced homeostasis, and perturbations of such can lead to the development of disease. Here, we review de novo and dietary fatty acid metabolism and highlight recent advances in our understanding of the relationship between dietary influences and genetic variation in fatty acid metabolism and their role in chronic diseases. PMID:24511462

  7. [Adult identical twins with moyamoya disease].

    PubMed

    Kashihara, M; Oki, H; Sasaki, K; Soga, T; Ueda, S; Matsumoto, K

    1984-11-01

    Adult identical twins with Moyamoya disease are reported. Laboratory examinations such as blood types, AB, Rh(+), HLA (human leucocytic antigen) analysis [AW26(9), A26(10), BW62(15), BW61(40), CW3], and finger prints, and hairs confirmed that two patients were identical twins. Both had normal serum immunoglobulin levels and no anti-DNA antibodies. Patient No. 1, a 39-year-old female, was admitted to our service with chief complaints of nausea, vomiting and left hemiparesis with sudden onset on Oct 31, 1981. The patient had an episode of tetraplegia that occurred suddenly at 4 years of her age and lasted about a week. Motor weakness had completely disappeared but moderate mental retardation remained. She had been employed just prior to this attack. CT and angiographic examinations revealed ventricular hemorrhage with Moyamoya disease, which had miliary aneurysm in the branch of the right posterior choroidal artery. The operation of encephalomyosynangiosis was performed on her left hemisphere. The postoperative course was uneventful. Patient No. 2, the twin sister of patient No. 1, was in good health and mental state until 19 years of her age, when she suddenly lost consciousness and developed hemiparesis. After this attack, her motor function had recovered well. However, mental ability gradually deteriorated and she was admitted to a psychiatric ward. CT examination and angiographic studies were performed on Oct 12, 1982, and she was diagnosed as having Moyamoya disease.(ABSTRACT TRUNCATED AT 250 WORDS)

  8. The role of RNA metabolism in neurological diseases

    PubMed Central

    Abou Al-Shaar, H; Shariff, RK; Albakr, A

    2015-01-01

    Abstract Neurodegenerative disorders are commonly encountered in medical practices. Such diseases can lead to major morbidity and mortality among the affected individuals. The molecular pathogenesis of these disorders is not yet clear. Recent literature has revealed that mutations in RNA-binding proteins are a key cause of several human neuronal-based diseases. This review discusses the role of RNA metabolism in neurological diseases with specific emphasis on roles of RNA translation and microRNAs in neurodegeneration, RNA-mediated toxicity, repeat expansion diseases and RNA metabolism, molecular pathogenesis of amyotrophic lateral sclerosis and frontotemporal dementia, and neurobiology of survival motor neuron (SMN) and spinal muscular atrophy. PMID:27785391

  9. Metabolic resting-state brain networks in health and disease.

    PubMed

    Spetsieris, Phoebe G; Ko, Ji Hyun; Tang, Chris C; Nazem, Amir; Sako, Wataru; Peng, Shichun; Ma, Yilong; Dhawan, Vijay; Eidelberg, David

    2015-02-24

    The delineation of resting state networks (RSNs) in the human brain relies on the analysis of temporal fluctuations in functional MRI signal, representing a small fraction of total neuronal activity. Here, we used metabolic PET, which maps nonfluctuating signals related to total activity, to identify and validate reproducible RSN topographies in healthy and disease populations. In healthy subjects, the dominant (first component) metabolic RSN was topographically similar to the default mode network (DMN). In contrast, in Parkinson's disease (PD), this RSN was subordinated to an independent disease-related pattern. Network functionality was assessed by quantifying metabolic RSN expression in cerebral blood flow PET scans acquired at rest and during task performance. Consistent task-related deactivation of the "DMN-like" dominant metabolic RSN was observed in healthy subjects and early PD patients; in contrast, the subordinate RSNs were activated during task performance. Network deactivation was reduced in advanced PD; this abnormality was partially corrected by dopaminergic therapy. Time-course comparisons of DMN loss in longitudinal resting metabolic scans from PD and Alzheimer's disease subjects illustrated that significant reductions appeared later for PD, in parallel with the development of cognitive dysfunction. In contrast, in Alzheimer's disease significant reductions in network expression were already present at diagnosis, progressing over time. Metabolic imaging can directly provide useful information regarding the resting organization of the brain in health and disease.

  10. Bartonella endocarditis mimicking adult Still's disease.

    PubMed

    De Clerck, K F; Van Offel, J F; Vlieghe, E; Van Marck, E; Stevens, W J

    2008-01-01

    We describe the case of a 39-year-old Caucasian woman who was admitted to the University Hospital of Antwerp with a clinical picture suggestive of adult Still's disease. Even though a transoesophageal echocardiography showed endocarditis of the aortic valve, blood cultures remained negative. Additional serological testing revealed a positive result for Bartonella henselae. Histology of the supraclavicular lymph node showed a reactive lymph node with a positive polymerase chain reaction (PCR) for Bartonella henselae. Prednisolone treatment was started in a dosage of 10 mg per day and rifampicin 600 mg/d in combination with doxycyclin 200 mg/d was given for 6 months. During therapy the patient gradually improved and signs of endocarditis disappeared on echocardiography. PMID:18714850

  11. Pregnancy in women with inherited metabolic disease

    PubMed Central

    2015-01-01

    An increasing number of women with rare inherited disorders of metabolism are becoming pregnant. Whilst, in general, outcomes for women and their children are good, there are issues that need to be considered. Due to the rarity of many conditions, there is limited specific guidance available on best management. Prepregnancy counselling with information on inheritance, options for reproduction, teratogenicity risk, potential impact on maternal health and long-term health of children should be offered. With appropriate specialist management, the teratogenic risk of conditions such as maternal phenylketonuria (PKU) can be eliminated, and the risk of metabolic decompensation in other disorders of intoxication or energy metabolism significantly reduced. Newer therapies, such as enzyme replacement therapy, appear to be safe in pregnancy, but specific advice should be sought. Multidisciplinary management, and close liaison between obstetricians and other specialists is required for women in whom there is cardiac, renal, respiratory, joint or other organ involvement. PMID:27512458

  12. [Updates on Lifestyle-Related Diseases and Bone Metabolism. Bidirectional relationship between lifestyle-related diseases and bone metabolism].

    PubMed

    Sato, Shingo; Takeda, Shu

    2014-11-01

    Lifestyle-related diseases such as diabetes mellitus, chronic kidney disease, and hypertension were previously considered to be unrelated to osteoporosis. However, recent investigations have demonstrated that lifestyle-related diseases have a significant effect on the regulation of bone metabolism. In addition, it has been also revealed that osteocalcin or fibroblast growth factor 23 (FGF23) , which is produced by osteoblasts, has an important role in glucose metabolism, fat metabolism, or calcium homeostasis. These findings suggest that bone is not only a target organ of hormones but also involved in regulating other organs as an endocrine organ. This review introduces such a bidirectional relationship between several lifestyle-related diseases and bone metabolism. PMID:25355142

  13. [Updates on Lifestyle-Related Diseases and Bone Metabolism. Bidirectional relationship between lifestyle-related diseases and bone metabolism].

    PubMed

    Sato, Shingo; Takeda, Shu

    2014-11-01

    Lifestyle-related diseases such as diabetes mellitus, chronic kidney disease, and hypertension were previously considered to be unrelated to osteoporosis. However, recent investigations have demonstrated that lifestyle-related diseases have a significant effect on the regulation of bone metabolism. In addition, it has been also revealed that osteocalcin or fibroblast growth factor 23 (FGF23) , which is produced by osteoblasts, has an important role in glucose metabolism, fat metabolism, or calcium homeostasis. These findings suggest that bone is not only a target organ of hormones but also involved in regulating other organs as an endocrine organ. This review introduces such a bidirectional relationship between several lifestyle-related diseases and bone metabolism.

  14. Gamma images in benign and metabolic bone diseases: volume 1

    SciTech Connect

    Sy, W.M.

    1981-01-01

    Volume 1 of ''Gamma images in benign and metabolic bone diseases'' comprises chapters devoted to: general remarks and considerations, radiopharmaceuticals, Paget disease, osteomyelitis, trauma, benign bone tumors, chronic renal dialysis, acute renal failure, osteomalacia and rickets, and osteoporosis. Although published in 1981, the most recent references in the book were 1978 and most are 1977 or earlier. One of the strongest aspects of the volume are tables which categorize diseases, pathophysiology of disease, and image abnormalities. (JMT)

  15. Bile Acid Signaling in Metabolic Disease and Drug Therapy

    PubMed Central

    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

  16. The metabolic consequences of thyroxine replacement in adult hypopituitary patients.

    PubMed

    Filipsson Nyström, Helena; Feldt-Rasmussen, Ulla; Kourides, Ione; Popovic, Vera; Koltowska-Häggström, Maria; Jonsson, Björn; Johannsson, Gudmundur

    2012-12-01

    The metabolic consequences of thyroxine replacement in patients with central hypothyroidism (CH) need to be evaluated. The aim was to examine the outcome of thyroxine replacement in CH. Adult hypopituitary patients (n = 1595) with and without CH from KIMS (Pfizer International Metabolic Database) were studied before and after 2 years of GH replacement. CH patients (CH, n = 1080) were compared with TSH sufficient patients (TSHsuff n = 515) as one group and divided by thyroxine dose/kg/day into tertiles (CHlow-mid-high). Anthropometry, fasting glucose, glycosylated haemoglobin (HbA1c), blood pressure, lipids, IGF-I SDS, quality of life and morbidity were studied. Analyses were standardized for gender, age, number and types of pituitary insufficiencies, stimulated GH peak, age at GH deficiency onset, aetiologies and, when appropriate, for weight and GH dose. At baseline, TSHsuff patients did not differ from CH or CHmid in any outcome. CHlow (≤ 1.18 μg thyroxine/kg/day) had increased weight, BMI and larger waist circumference (WC), CHhigh (≥ 1.58 μg thyroxine/kg/day) had lower weight, BMI, WC and IGF-I than TSHsuff and compared to their predicted weights, BMIs and WCs. For every 0.1 μg/kg/day increase of thyroxine dose, body weight decreased 1.0 kg, BMI 0.3 kg/m(2), and WC 0.65 cm. The GH sensitivity of the CH group was higher (0.76 ± 0.56 SDS/mg GH) than that of TSHsuff patients (0.58 ± 0.64 SDS/mg GH), P < 0.001. The middle thyroxine dose (1.19-1.57 μg/kg/day) seems to be the most physiological. This is equivalent to 70, 100, 125 μg thyroxine/day for hypopituitary patients of 50, 70 or 90 kg weight, respectively.

  17. Folate: metabolism, genes, polymorphisms and the associated diseases.

    PubMed

    Nazki, Fakhira Hassan; Sameer, Aga Syed; Ganaie, Bashir Ahmad

    2014-01-01

    Folate being an important vitamin of B Complex group in our diet plays an important role not only in the synthesis of DNA but also in the maintenance of methylation reactions in the cells. Folate metabolism is influenced by several processes especially its dietary intake and the polymorphisms of the associated genes involved. Aberrant folate metabolism, therefore, affects both methylation as well as the DNA synthesis processes, both of which have been implicated in the development of various diseases. This paper reviews the current knowledge of the processes involved in folate metabolism and consequences of deviant folate metabolism, particular emphasis is given to the polymorphic genes which have been implicated in the development of various diseases in humans, like vascular diseases, Down's syndrome, neural tube defects, psychiatric disorders and cancers. PMID:24091066

  18. [Nutrition of pregnant women: consequences for fetal growth and adult diseases].

    PubMed

    Weber, M; Ayoubi, J-M; Picone, O

    2015-01-01

    The developmental origins of human adult disease are thought to be secondary to a perturbation of the embryonic or fetal development, which leads to metabolic disorders such as diabetes or hypertension at adulthood. Maternal undernutrition or overnutrition, repeated glucocorticosteroids administered to the mother, or placental dysfunction are the most frequently considered causal factors. Therefore, it is necessary that the pediatrician is aware of these phenomena, as this knowledge may contribute to the prevention of adult diseases. Little is known yet, however, on the pathophysiological or epigenetic mechanisms that lead to theses observations, and more studies are needed both in humans and animal models. PMID:25440770

  19. C(1) metabolism and CVD outcomes in older adults.

    PubMed

    McNulty, Helene; Strain, J J; Pentieva, Kristina; Ward, Mary

    2012-05-01

    CVD is the most common cause of death in people over 65 years. This review considers the latest evidence for a potential protective effect of C(1) donors (folate and the metabolically related B-vitamins) in CVD. Such an effect may or may not be mediated via the role of these nutrients in maintaining plasma homocysteine concentrations within a desirable range. Despite predictions from epidemiological studies that lowering plasma homocysteine would reduce cardiovascular risk, several secondary prevention trials in at-risk patients published since 2004 have failed to demonstrate a benefit of homocysteine-lowering therapy with B-vitamins on CVD events generally. All these trials were performed in CVD patients with advanced disease; thus current evidence suggests that intervention with high-dose folic acid is of no benefit in preventing another event, at least in the case of heart disease. The evidence at this time, however, is stronger for stroke, with meta-analyses of randomised trials showing that folic acid reduces the risk of stroke, particularly in people with no history of stroke. Genetic studies provide convincing evidence to support a causal relationship between sub-optimal B-vitamin status and CVD. People homozygous for the common C677T variant in the gene encoding the folate-metabolising enzyme, methylenetetrahydrofolate reductase (MTHFR), typically have a 14-21% higher risk of CVD. Apart from folate, riboflavin is required as a co-factor for MTHFR. New evidence shows that riboflavin intervention results in marked lowering of blood pressure, specifically in patients with the MTHFR 677TT genotype. This novel gene-nutrient interaction may provide insights as to the mechanism that links C(1) metabolism with CVD outcomes. PMID:22152927

  20. Glucose metabolism derangements in adults with the MELAS m.3243A>G mutation.

    PubMed

    El-Hattab, Ayman W; Emrick, Lisa T; Hsu, Jean W; Chanprasert, Sirisak; Jahoor, Farook; Scaglia, Fernando; Craigen, William J

    2014-09-01

    The m.3243A>G mutation in the mitochondrial gene MT-TL1 leads to a wide clinical spectrum ranging from asymptomatic carriers to MELAS (mitochondrial encephalomyopathy, lactic acidosis, and stroke-like episodes) at the severe end. Diabetes mellitus (DM) occurs in mitochondrial diseases, with the m.3243A>G mutation being the most common mutation associated with mitochondrial DM. The pathogenesis of mitochondrial DM remains largely unknown, with previous studies suggesting that impaired insulin secretion is the major factor. In this study we used stable isotope infusion techniques to assess glucose metabolism in vivo and under physiological conditions in 5 diabetic and 11 non-diabetic adults with the m.3243A>G mutation and 10 healthy adult controls. Our results revealed increased glucose production due to increased gluconeogenesis in both diabetic and non-diabetic subjects with the m.3243A>G mutation. In addition, diabetic subjects demonstrated insulin resistance and relative insulin deficiency, resulting in an inability to increase glucose oxidation which can explain the development of DM in these subjects. Non-diabetic subjects showed normal insulin sensitivity; and therefore, they were able to increase their glucose oxidation rate. The ability to increase glucose utilization can act as a compensatory mechanism that explains why these subjects do not have DM despite the higher rate of glucose production. These results suggest that increased gluconeogenesis is not enough to cause DM and the occurrence of combined insulin resistance and relative insulin deficiency are needed to develop DM in individuals with the m.3243A>G mutation. Therefore, multiple defects in insulin and glucose metabolism are required for DM to occur in individuals with mitochondrial diseases. The results of this study uncover previously undocumented alterations in glucose metabolism in individuals with the m.3243A>G mutation that contribute significantly to our understanding of the pathogenesis

  1. Reduced Resting Metabolic Rate in Adults with Hemiparetic Chronic Stroke

    PubMed Central

    Serra, Monica C; Hafer-Macko, Charlene E; Ryan, Alice S

    2016-01-01

    Objective Resting metabolic rate (RMR) is the component of energy expenditure that explains the largest proportion of total daily energy requirements. Since RMR is determined largely by fat-free mass and a low RMR predicts weight gain in healthy adults, identifying the role of muscle atrophy following stroke on RMR may help identify ways to mitigate the development of obesity post-stroke. Methods Thirty-nine stroke survivors with chronic hemiparesis (mean ± SEM: age: 61 ± 1 years, latency from stroke: 107 ± 40 months, BMI: 31 ± 3 kg/m2) underwent DXA scans for measurement of body composition, including total, paretic, and non-paretic leg lean mass and fasted, 30-min indirect calorimetry for measurement of RMR. Result Predicted RMR was calculated by the Mifflin-St Jeor equation, which considers weight, height, and age for both men and women. RMR was 14% lower than predicted (1438 ± 45 vs. 1669 ± 38 kcals/24 hrs; P<0.01). Total (r=0.73, P<0.01), paretic (r=0.72, P<0.01) and non-paretic (r=0.67, P<0.01) leg lean mass predicted RMR. Conclusion These data indicate that muscle atrophy post stroke may lead to a reduced RMR. This substantiates the need to attenuate the loss of lean mass after a stroke to prevent declines in RMR and possible weight gain common post-stroke. PMID:26973796

  2. A review of the economics of adult congenital heart disease.

    PubMed

    Seckeler, Michael D; Thomas, Ian D; Andrews, Jennifer; Joiner, Keith; Klewer, Scott E

    2016-01-01

    Adults living with congenital heart disease (CHD) now outnumber children with the disease. Thanks to medical advances over the past 75 years, many of these fatal childhood heart problems have changed to chronic medical conditions. As the population of adults with CHD increases, they will require increasingly complex medical, surgical and catheter-based therapies. In addition, social burdens including education, employment and insurability, which increase the societal costs of adult CHD, are now being recognized for adults living with CHD. This review summarizes the available literature on the economics of adult CHD.

  3. Examining Variations of Resting Metabolic Rate of Adults: A Public Health Perspective

    PubMed Central

    McMurray, Robert G.; Soares, Jesus; Caspersen, Carl J.; McCurdy, Thomas

    2015-01-01

    Purpose There has not been a recent comprehensive effort to examine existing studies on the resting metabolic rate (RMR) of adults to identify the effect of common population demographic and anthropometric characteristics. Thus, we reviewed the literature on RMR (kcal·kg−1·h−1) to determine the relationship of age, sex, and obesity status to RMR as compared with the commonly accepted value for the metabolic equivalent (MET; e.g., 1.0 kcal·kg−1·h−1). Methods Using several databases, scientific articles published from 1980 to 2011 were identified that measured RMR, and from those, others dating back to 1920 were identified. One hundred and ninety-seven studies were identified, resulting in 397 publication estimates of RMR that could represent a population subgroup. Inverse variance weighting technique was applied to compute means and 95% confidence intervals (CI). Results The mean value for RMR was 0.863 kcal·kg−1·h−1 (95% CI = 0.852–0.874), higher for men than women, decreasing with increasing age, and less in overweight than normal weight adults. Regardless of sex, adults with BMI ≥ 30 kg·m−2 had the lowest RMR (<0.741 kcal·kg−1·h−1). Conclusions No single value for RMR is appropriate for all adults. Adhering to the nearly universally accepted MET convention may lead to the overestimation of the RMR of approximately 10%for men and almost 15% for women and be as high as 20%–30% for some demographic and anthropometric combinations. These large errors raise questions about the longstanding adherence to the conventional MET value for RMR. Failure to recognize this discrepancy may result in important miscalculations of energy expended from interventions using physical activity for diabetes and other chronic disease prevention efforts. PMID:24300125

  4. Glucose Metabolism: A Sweet Relief of Alzheimer's Disease.

    PubMed

    Duran-Aniotz, Claudia; Hetz, Claudio

    2016-09-12

    Patients and individuals at risk for Alzheimer's disease show reduced glucose metabolism in the brain. A new study takes advantage of a fly model of Alzheimer's disease to demonstrate that enhancing glucose uptake in neurons has strong neuroprotective effects involving improved proteostasis. PMID:27623263

  5. [Bone diseases caused by impaired glucose and lipid metabolism].

    PubMed

    Kanazawa, Ippei; Sugimoto, Toshitsugu

    2013-11-01

    The number of patients with lifestyle-related diseases is rapidly increasing in Japan. Metabolic syndrome caused by abdominal fat accumulation induces diabetes mellitus, dyslipidemia, and hypertension, resulting in an increase in cardiovascular diseases. On the other hand, recent studies have shown that the lifestyle-related diseases are risk factors of osteoporotic fractures. Although it remains still unclear how metabolic disorders affect bone tissue, oxidative stress and/or glycation stress might directly have negative impacts on bone tissue and increase the risk of fractures. In this review, we describe the association of diabetes mellitus and dyslipidemia with the fracture risk through oxidative stress and glycation stress.

  6. Advances in the Care of Adults With Congenital Heart Disease.

    PubMed

    Nasr, Viviane G; Kussman, Barry D

    2015-09-01

    The significant decline in mortality among children and adolescents with congenital heart disease (CHD) is associated with an increasing prevalence of CHD in adults, particularly those with moderate to severe defects. As a significant percentage of adolescents and young adults are lost to follow-up in the transition from pediatric to adult care, they may present for elective procedures with substantial CHD-associated morbidity. In addition to the specific cardiac defect, the procedures performed, and the current pathophysiological status, several factors should be considered when managing the adult with CHD. These include the type of setting (adult vs pediatric institution); surgeon (pediatric vs adult cardiac surgeon); coexisting diseases associated with CHD, such as coronary artery disease, hepatic dysfunction, renal dysfunction, cerebrovascular accidents, myopathy, and coagulation disorders; acquired diseases of aging; pregnancy; and psychosocial functioning. The current status of the management of common and important congenital cardiac defects is also described. PMID:25542866

  7. Modeling Metabolism and Disease in Bioarcheology

    PubMed Central

    Qualls, Clifford; Appenzeller, Otto

    2015-01-01

    We examine two important measures that can be made in bioarcheology on the remains of human and vertebrate animals. These remains consist of bone, teeth, or hair; each shows growth increments and each can be assayed for isotope ratios and other chemicals in equal intervals along the direction of growth. In each case, the central data is a time series of measurements. The first important measures are spectral estimates in spectral analyses and linear system analyses; we emphasize calculation of periodicities and growth rates as well as the comparison of power in bands. A low frequency band relates to the autonomic nervous system (ANS) control of metabolism and thus provides information about the life history of the individual of archeological interest. Turning to nonlinear system analysis, we discuss the calculation of SM Pinus' approximate entropy (ApEn) for short or moderate length time series. Like the concept that regular heart R-R interval data may indicate lack of health, low values of ApEn may indicate disrupted metabolism in individuals of archeological interest and even that a tipping point in deteriorating metabolism may have been reached just before death. This adds to the list of causes of death that can be determined from minimal data. PMID:26347356

  8. Modeling Metabolism and Disease in Bioarcheology.

    PubMed

    Qualls, Clifford; Appenzeller, Otto

    2015-01-01

    We examine two important measures that can be made in bioarcheology on the remains of human and vertebrate animals. These remains consist of bone, teeth, or hair; each shows growth increments and each can be assayed for isotope ratios and other chemicals in equal intervals along the direction of growth. In each case, the central data is a time series of measurements. The first important measures are spectral estimates in spectral analyses and linear system analyses; we emphasize calculation of periodicities and growth rates as well as the comparison of power in bands. A low frequency band relates to the autonomic nervous system (ANS) control of metabolism and thus provides information about the life history of the individual of archeological interest. Turning to nonlinear system analysis, we discuss the calculation of SM Pinus' approximate entropy (ApEn) for short or moderate length time series. Like the concept that regular heart R-R interval data may indicate lack of health, low values of ApEn may indicate disrupted metabolism in individuals of archeological interest and even that a tipping point in deteriorating metabolism may have been reached just before death. This adds to the list of causes of death that can be determined from minimal data. PMID:26347356

  9. Obesity and metabolic disorders in adults with lower limb amputation.

    PubMed

    Kurdibaylo, S F

    1996-10-01

    Anthropometric and biochemical research was conducted on 94 subjects with various levels of lower limb amputation. The purpose of the work was to investigate the features of obesity progression and disorders of cholesterin metabolism, as well as to develop adequate training exercises. Anthropometric research was conducted by calipermetry; the biochemical research was done by various methods to determine exempt and total cholesterin and triglycerides in the blood serum. The research establishes the frequency of obesity progression relative to the level of amputation, as well as the features of the excessive body mass. Type 11A hyperlipoproteidemia was evident. It is characterized by rapid progress of atherosclerotic vascular disease and coronary disease (CD). Cyclic and acyclic exercises were developed for prophylaxis and therapy. Anthropometric research on the determination of body fat mass was conducted on 68 subjects with various levels of lower limb amputation. The nondirect method of measuring skin folds of several parts of the body was used to determine the extent of lipogenesis. Biochemical research of cholesterin metabolism was conducted on 26 subjects with lower limb amputation (a different group). Anthropometric research revealed an increase of body fat mass directly related to the level of amputation. The largest amount of fat in the body mass was noted for the subjects with bilateral transfemoral (above-knee) amputation or transfemoral plus transtibial (below-knee) amputation. Both groups averaged 25.9%. The body fat mass increased chiefly in the subcutaneous fat. Increase of the internal fat mass was less noticeable. The frequency of obesity progression in subjects with unilateral transtibial amputation equaled 37.9%; in subjects with transfemoral amputation, 48.0%; and in subjects with bilateral transfemoral or transfemoral plus transtibial amputation, 64.2%. Young subjects demonstrated obesity progression during the first year after amputation

  10. Vitamin-Dependent Methionine Metabolism and Alcoholic Liver Disease1

    PubMed Central

    Halsted, Charles H.; Medici, Valentina

    2011-01-01

    Emerging evidence indicates that ethanol-induced alterations in hepatic methionine metabolism play a central role in the pathogenesis of alcoholic liver disease (ALD). Because malnutrition is a universal clinical finding in this disease and hepatic methionine metabolism is dependent upon dietary folate and vitamins B-6 and B-12, ALD can be considered an induced nutritional disorder that is conditioned by alcohol abuse. The present review describes the etiologies of these 3 vitamin deficiencies in ALD and how they interact with chronic ethanol exposure to alter hepatic methionine metabolism. Subsequent sections focus on molecular mechanisms for the interactions of aberrant methionine metabolism with ethanol in the pathogenesis of ALD, in particular the role of S-adenosylmethionine (SAM) in regulating the epigenetic expressions of genes relevant to pathways of liver injury. The review will conclude with descriptions of studies on the efficacy of SAM in the treatment of ALD and with discussion of potentially fruitful future avenues of research. PMID:22332083

  11. Inflammation Meets Metabolic Disease: Gut Feeling Mediated by GLP-1.

    PubMed

    Zietek, Tamara; Rath, Eva

    2016-01-01

    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, such as 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 indicate 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. PMID:27148273

  12. Metabolic Profiling of Children Undergoing Surgery for Congenital Heart Disease

    PubMed Central

    Correia, Goncalo D. S.; Wooi Ng, Keng; Wijeyesekera, Anisha; Gala-Peralta, Sandra; Williams, Rachel; MacCarthy-Morrogh, S.; Jiménez, Beatriz; Inwald, David; Macrae, Duncan; Frost, Gary; Holmes, Elaine

    2015-01-01

    Objective: Inflammation and metabolism are closely interlinked. Both undergo significant dysregulation following surgery for congenital heart disease, contributing to organ failure and morbidity. In this study, we combined cytokine and metabolic profiling to examine the effect of postoperative tight glycemic control compared with conventional blood glucose management on metabolic and inflammatory outcomes in children undergoing congenital heart surgery. The aim was to evaluate changes in key metabolites following congenital heart surgery and to examine the potential of metabolic profiling for stratifying patients in terms of expected clinical outcomes. Design: Laboratory and clinical study. Setting: University Hospital and Laboratory. Patients: Of 28 children undergoing surgery for congenital heart disease, 15 underwent tight glycemic control postoperatively and 13 were treated conventionally. Interventions: Metabolic profiling of blood plasma was undertaken using proton nuclear magnetic resonance spectroscopy. A panel of metabolites was measured using a curve-fitting algorithm. Inflammatory cytokines were measured by enzyme-linked immunosorbent assay. The data were assessed with respect to clinical markers of disease severity (Risk Adjusted Congenital heart surgery score-1, Pediatric Logistic Organ Dysfunction, inotrope score, duration of ventilation and pediatric ICU-free days). Measurements and Main Results: Changes in metabolic and inflammatory profiles were seen over the time course from surgery to recovery, compared with the preoperative state. Tight glycemic control did not significantly alter the response profile. We identified eight metabolites (3-d-hydroxybutyrate, acetone, acetoacetate, citrate, lactate, creatine, creatinine, and alanine) associated with surgical and disease severity. The strength of proinflammatory response, particularly interleukin-8 and interleukin-6 concentrations, inversely correlated with PICU-free days at 28 days. The interleukin

  13. Inflammation Meets Metabolic Disease: Gut Feeling Mediated by GLP-1

    PubMed Central

    Zietek, Tamara; Rath, Eva

    2016-01-01

    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, such as 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 indicate 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. PMID:27148273

  14. Arsenic Metabolism in Children Differs From That in Adults

    PubMed Central

    Skröder Löveborn, Helena; Lu, Ying; Ahmed, Sultan; Kuehnelt, Doris; Raqib, Rubhana; Vahter, Marie

    2016-01-01

    Arsenic toxicity in adults is associated with methylation efficiency, influenced by factors such as gender, genetics, and nutrition. The aim of this study was to evaluate influencing factors for arsenic metabolism in children. For 488 children (9 years), whose mothers participated in a study on arsenic exposure during pregnancy (nested into the MINIMat trial) in rural Bangladesh, we measured urinary concentrations of inorganic arsenic (iAs) and its metabolites methylarsonic acid (MMA) and dimethylarsinic acid (DMA) by HPLC-HG-ICPMS. Methylation efficiency was assessed by relative amounts (%) of the metabolites. We evaluated the impact of factors such as maternal urinary metabolite pattern, arsenic exposure, gender, socioeconomic status, season of sampling, and nutritional factors, including erythrocyte selenium (Ery-Se), and plasma folate and vitamin B12. Children had higher %DMA and lower %iAs in urine compared to their mothers, unrelated to their lower exposure [median urinary arsenic (U-As) 53 vs 78 µg/l]. Surprisingly, selenium status (Ery-Se) was strongly associated with children’s arsenic methylation; an increase in Ery-Se from the 5–95th percentile was associated with: +1.8 percentage points (pp) for %iAs (P  =  .001), +1.4 pp for %MMA (P  =  .003), and −3.2 pp for %DMA (P  <  .001). Despite this, Ery-Se was positively associated with U-As (5–95th percentile: +41 µg/l, P  =  .026). As expected, plasma folate was inversely associated with %iAs (5–95th percentile: −1.9 pp, P  =  .001) and positively associated with %DMA (5–95th percentile: +2.2 pp, P  =  .008). Children methylated arsenic more efficiently than their mothers. Also influencing factors, mainly selenium and folate, differed. This warrants further research. PMID:27056082

  15. [Application of precision medicine in obesity and metabolic disease surgery].

    PubMed

    Wang, Cunchuan; Gao, Zhiguang

    2016-01-01

    The U. S. A. president Obama called for a new initiative to fund precision medicine during his State of Union Address on January 20th, 2015, which meant that the human medicine enters a new era. The meaning of "precision medicine" is significantly similar to the concept of precision obesity and metabolic disease surgery, which was proposed by the author in early August 2011. Nowadays, obesity and metabolic disease surgery has been transformed from open surgery to laparoscopic surgery, the extensive mode to the precision mode. The key value concept is to minimize postoperative complication, minimize postoperative hospital stay and obtain the best effect of weight loss by accurate preoperative assessment, delicate operation, excellent postoperative management and scientific follow-up. The precision obesity and metabolic disease surgery has more development space in the future. PMID:26797833

  16. [Kimura's disease: an unrecognized cause of adult-onset nephrotic syndrome with minimal change disease].

    PubMed

    Shehwaro, N; Langlois, A-L; Gueutin, V; Debchi, L; Charlotte, F; Rouvier, P; Rottembourg, J; Izzedine, H

    2014-02-01

    Kimura's disease (KD) is an angiolymphoid proliferative disorder of soft tissue with eosinophilia, with a predilection for head and neck regions in young Oriental men. Kidney disease is thought to be rare in KD. About a case of adult-onset nephrotic syndrome with minimal change disease, we comment Kimura's disease and its associated kidney damage. Kimura disease should be suspected and included in the diagnosis of adult-onset nephrotic syndrome with minimal change disease.

  17. The metabolic syndrome as a concept of adipose tissue disease.

    PubMed

    Oda, Eiji

    2008-07-01

    The metabolic syndrome is a constellation of interrelated metabolic risk factors that appear to directly promote the development of diabetes and cardiovascular disease. However, in 2005, the American Diabetes Association and the European Association for the Study of Diabetes jointly stated that no existing definition of the metabolic syndrome meets the criteria of a syndrome, and there have been endless debates on the pros and cons of using the concept of this syndrome. The controversy may stem from confusion between the syndrome and obesity. Obesity is an epidemic, essentially contagious disease caused by an environment of excess nutritional energy and reinforced by deeply rooted social norms. The epidemic of obesity should be prevented or controlled by social and political means, similar to the approaches now being taken to combat global warming. The diagnosis of metabolic syndrome is useless for this public purpose. The purpose of establishing criteria for diagnosing metabolic syndrome is to find individuals who are at increased risk of diabetes and cardiovascular disease and who require specific therapy including diet and exercise. The syndrome may be an adipose tissue disease different from obesity; in that case, it would be characterized by inflammation clinically detected through systemic inflammatory markers such as high-sensitivity C-reactive protein and insulin resistance reflecting histological changes in adipose tissue. However, many problems in defining the optimal diagnostic criteria remain unresolved.

  18. Cardiac rehabilitation programs improve metabolic parameters in patients with the metabolic syndrome and coronary heart disease.

    PubMed

    Pérez, Ignacio P; Zapata, Maria A; Cervantes, Carlos E; Jarabo, Rosario M; Grande, Cristina; Plaza, Rose; Garcia, Sara; Rodriguez, Miriam L; Crespo, Silvia; Perea, Jesús

    2010-05-01

    This study was performed to determine the effectiveness of a cardiac rehabilitation and exercise training program on metabolic parameters and coronary risk factors in patients with the metabolic syndrome and coronary heart disease. The study involved 642 patients with coronary heart disease. Of them, 171 (26.7%) fulfilled criteria for the metabolic syndrome. Clinical data, laboratory tests, and exercise testing were performed before and after the program, which lasted 2 to 3 months. Except for waist circumference, there were no significant differences between groups; blood pressure, high-density lipoprotein cholesterol, triglycerides, and fasting glucose improvements during the follow-up were higher in patients with the metabolic syndrome (all P<.001). At study end, in patients with the metabolic syndrome, functional capacity increased by 26.45% ( P<.001), as measured by metabolic equivalents, with a slight increase of 1.25% ( P=not significant) in the double product. Patients with the metabolic syndrome who took part in this secondary prevention program reported improvements in cardiovascular risk profile and functional capacity.

  19. Altered cholesterol and fatty acid metabolism in Huntington disease.

    PubMed

    Block, Robert C; Dorsey, E Ray; Beck, Christopher A; Brenna, J Thomas; Shoulson, Ira

    2010-01-01

    Huntington disease is an autosomal dominant neurodegenerative disorder characterized by behavioral abnormalities, cognitive decline, and involuntary movements that lead to a progressive decline in functional capacity, independence, and ultimately death. The pathophysiology of Huntington disease is linked to an expanded trinucleotide repeat of cytosine-adenine-guanine (CAG) in the IT-15 gene on chromosome 4. There is no disease-modifying treatment for Huntington disease, and novel pathophysiological insights and therapeutic strategies are needed. Lipids are vital to the health of the central nervous system, and research in animals and humans has revealed that cholesterol metabolism is disrupted in Huntington disease. This lipid dysregulation has been linked to specific actions of the mutant huntingtin on sterol regulatory element binding proteins. This results in lower cholesterol levels in affected areas of the brain with evidence that this depletion is pathologic. Huntington disease is also associated with a pattern of insulin resistance characterized by a catabolic state resulting in weight loss and a lower body mass index than individuals without Huntington disease. Insulin resistance appears to act as a metabolic stressor attending disease progression. The fish-derived omega-3 fatty acids, eicosapentaenoic acid and docosahexaenoic acid, have been examined in clinical trials of Huntington disease patients. Drugs that combat the dysregulated lipid milieu in Huntington disease may help treat this perplexing and catastrophic genetic disease.

  20. Effect of maternal diet on the epigenome: implications for human metabolic disease.

    PubMed

    Lillycrop, Karen A

    2011-02-01

    The rapid increase in the incidence of chronic non-communicable diseases over the past two decades cannot be explained solely by genetic and adult lifestyle factors. There is now considerable evidence that the fetal and early postnatal environment also strongly influences the risk of developing such diseases in later life. Human studies have shown that low birth weight is associated with an increased risk of CVD, type II diabetes, obesity and hypertension, although recent studies have shown that over-nutrition in early life can also increase susceptibility to future metabolic disease. These findings have been replicated in a variety of animal models, which have shown that both maternal under- and over-nutrition can induce persistent changes in gene expression and metabolism within the offspring. The mechanism by which the maternal nutritional environment induces such changes is beginning to be understood and involves the altered epigenetic regulation of specific genes. The demonstration of a role for altered epigenetic regulation of genes in the developmental induction of chronic diseases raises the possibility that nutritional or pharmaceutical interventions may be used to modify long-term cardio-metabolic disease risk and combat this rapid rise in chronic non-communicable diseases.

  1. Endoplasmic Reticulum Stress and the Inflammatory Basis of Metabolic Disease

    PubMed Central

    Hotamisligil, Gökhan S.

    2010-01-01

    The endoplasmic reticulum (ER) is the major site in the cell for protein folding and trafficking and is central to many cellular functions. Failure of the ER's adaptive capacity results in activation of the unfolded protein response (UPR), which intersects with many different inflammatory and stress signaling pathways. These pathways are also critical in chronic metabolic diseases such as obesity, insulin resistance, and type 2 diabetes. The ER and related signaling networks are emerging as a potential site for the intersection of inflammation and metabolic disease. PMID:20303879

  2. Cardiovascular Disease Risk of Abdominal Obesity versus Metabolic Abnormalities

    PubMed Central

    Wildman, Rachel P.; McGinn, Aileen P.; Lin, Juan; Wang, Dan; Muntner, Paul; Cohen, Hillel W.; Reynolds, Kristi; Fonseca, Vivian; Sowers, MaryFran R.

    2011-01-01

    It remains unclear whether abdominal obesity increases cardiovascular disease (CVD) risk independent of the metabolic abnormalities which often accompany it. Therefore, the objective of the current study was to evaluate the independent effects of abdominal obesity versus metabolic syndrome and diabetes on the risk for incident coronary heart disease and stroke. The Framingham Offspring, Atherosclerosis Risk in Communities, and Cardiovascular Health studies were pooled to assess the independent effects of abdominal obesity (waist circumference >102 cm for men and >88 cm for women) versus metabolic syndrome (excluding the waist circumference criterion) and diabetes on risk for incident coronary heart disease and stroke in 20,298 men and women aged ≥45 years. The average follow-up was 8.3 (standard deviation 1.9) years. There were 1,766 CVD events. After adjustment for demographic factors, smoking, alcohol intake, number of metabolic syndrome components and diabetes, abdominal obesity was not significantly associated with an increased risk of CVD (hazard ratio [95% confidence interval] 1.09 [0.98, 1.20]). However, after adjustment for demographics, smoking, alcohol intake, and abdominal obesity, having 1–2 metabolic syndrome components, the metabolic syndrome, and diabetes were each associated with a significantly increased risk of CVD (2.12 [1.80, 2.50], 2.82 [1.92, 4.12] and 5.33 [3.37, 8.41], respectively). Although abdominal obesity is an important clinical tool for identification of individuals likely to possess metabolic abnormalities, these data suggest that the metabolic syndrome and diabetes are considerably more important prognostic indicators of CVD risk. PMID:20725064

  3. Turner's syndrome presenting as metabolic bone disease

    PubMed Central

    Kamalanathan, Sadishkumar; Balachandran, Karthik; Ananthakrishnan, Ramesh; Hamide, Abdoul

    2012-01-01

    Turner's syndrome is a genetic disorder with a complete or partial absence of one X chromosome with characteristic phenotypic features. The prevalence of renal anomalies in turner syndrome is 30–40%. However, the renal function is usually normal. We report a case of Turner's syndrome presenting with chronic kidney disease and renal osteodystrophy. PMID:22837932

  4. Relationship between plasma resistin concentrations, inflammatory chemokines, and components of the metabolic syndrome in adults.

    PubMed

    Aquilante, Christina L; Kosmiski, Lisa A; Knutsen, Shannon D; Zineh, Issam

    2008-04-01

    Recent data suggest that resistin, an adipocyte-derived cytokine, has a putative role in inflammatory processes and metabolic derangements. In vitro data suggest that resistin stimulates the production of inflammatory chemokines, yet the relationship in vivo is largely unknown. The purpose of this study was to determine if a relationship exists between plasma resistin concentrations, plasma inflammatory chemokine aged concentrations (ie, monocyte chemoattractant protein 1 [MCP-1] and epithelial neutrophil activator 78 [ENA-78]), and components of the metabolic syndrome in nondiabetic subjects without known cardiovascular disease (CVD). Plasma samples were obtained from nondiabetic subjects (N = 123) aged 18 to 55 years without known CVD or CVD risk equivalents. The presence of the metabolic syndrome was assessed using consensus guidelines. Fasting plasma resistin, MCP-1, ENA-78, and high-sensitivity C-reactive protein (hs-CRP) concentrations were analyzed. The study population consisted of 67.5% women and 68.3% Caucasians (mean age = 44 +/- 7 years and mean body mass index = 33.3 +/- 6 kg/m(2)). The metabolic syndrome was present in 46.3% of study participants. Resistin concentrations were significantly correlated with white blood cell count (r = 0.326, P < .001), hs-CRP concentrations (r = 0.293, P = .005), MCP-1 concentrations (r = 0.251, P = .005), body mass index (r = 0.193, P = .033), and high-density lipoprotein cholesterol (r = -0.182, P = .044). Resistin concentrations were 1.21 times higher in subjects with the metabolic syndrome compared with those without the metabolic syndrome (P = .003). In stepwise regression analysis, white blood cell count (P < .001) and MCP-1 concentrations (P = .002) were significantly associated with resistin concentrations, independent of hs-CRP, sex, body mass index, presence of the metabolic syndrome, and high-density lipoprotein cholesterol. Data from our cross-sectional study demonstrate that plasma resistin concentrations

  5. Metabolic biomarkers for predicting cardiovascular disease

    PubMed Central

    Montgomery, Jana E; Brown, Jeremiah R

    2013-01-01

    Cardiac and peripheral vascular biomarkers are increasingly becoming targets of both research and clinical practice. As of 2008, cardiovascular-related medical care accounts for greater than 20% of all the economic costs of illness in the United States. In the age of burgeoning financial pressures on the entire health care system, never has it been more important to try to understand who is at risk for cardiovascular disease in order to prevent new events. In this paper, we will discuss the cost of cardiovascular disease to society, clarify the definition of and need for biomarkers, offer an example of a current biomarker, namely high-sensitivity C-reactive protein, and finally examine the approval process for utilizing these in clinical practice. PMID:23386789

  6. Mitochondria in metabolic disease: getting clues from proteomic studies.

    PubMed

    Peinado, Juan R; Diaz-Ruiz, Alberto; Frühbeck, Gema; Malagon, Maria M

    2014-03-01

    Mitochondria play a key role as major regulators of cellular energy homeostasis, but in the context of mitochondrial dysfunction, mitochondria may generate reactive oxidative species and induce cellular apoptosis. Indeed, altered mitochondrial status has been linked to the pathogenesis of several metabolic disorders and specially disorders related to insulin resistance, such as obesity, type 2 diabetes, and other comorbidities comprising the metabolic syndrome. In the present review, we summarize information from various mitochondrial proteomic studies of insulin-sensitive tissues under different metabolic states. To that end, we first focus our attention on the pancreas, as mitochondrial malfunction has been shown to contribute to beta cell failure and impaired insulin release. Furthermore, proteomic studies of mitochondria obtained from liver, muscle, and adipose tissue are summarized, as these tissues constitute the primary insulin target metabolic tissues. Since recent advances in proteomic techniques have exposed the importance of PTMs in the development of metabolic disease, we also present information on specific PTMs that may directly affect mitochondria during the pathogenesis of metabolic disease. Specifically, mitochondrial protein acetylation, phosphorylation, and other PTMs related to oxidative damage, such as nitrosylation and carbonylation, are discussed.

  7. Knowledge of Metabolic Syndrome in Chinese Adults: Implications for Health Education

    ERIC Educational Resources Information Center

    Lo, Sally Wai Sze; Chair, Sek Ying; Lee, Iris Fung Kam

    2016-01-01

    Objective: The objective of this study was to assess knowledge of metabolic syndrome (MS) among Chinese adults and provide directions for designing healthcare promotion schemes for improving MS awareness in the community. Design: The study adopted a cross-sectional design and a convenience sampling method. Method: Chinese adults aged 18-65 years…

  8. Biotin in metabolism and its relationship to human disease.

    PubMed

    Pacheco-Alvarez, Diana; Solórzano-Vargas, R Sergio; Del Río, Alfonso León

    2002-01-01

    Biotin, a water-soluble vitamin, is used as cofactor of enzymes involved in carboxylation reactions. In humans, there are five biotin-dependent carboxylases: propionyl-CoA carboxylase; methylcrotonyl-CoA carboxylase; pyruvate carboxylase, and two forms of acetyl-CoA carboxylase. These enzymes catalyze key reactions in gluconeogenesis, fatty acid metabolism, and amino acid catabolism; thus, biotin plays an essential role in maintaining metabolic homeostasis. In recent years, biotin has been associated with several diseases in humans. Some are related to enzyme deficiencies involved in biotin metabolism. However, not all biotin-responsive disorders can be explained based on the classical role of the vitamin in cell metabolism. Several groups have suggested that biotin may be involved in regulating transcription or protein expression of different proteins. Biotinylation of histones and triggering of transduction signaling cascades have been suggested as underlying mechanisms behind these non-classical biotin-deficiency manifestation in humans.

  9. A Metabolic Study of Huntington’s Disease

    PubMed Central

    Kalliolia, Eirini; Ottolenghi, Chris; Hindmarsh, Peter; Hill, Nathan R.; Costelloe, Seán J.; Martin, Nicholas G.; Positano, Vincenzo; Watt, Hilary C.; Frost, Chris; Björkqvist, Maria; Warner, Thomas T.

    2016-01-01

    Background Huntington’s disease patients have a number of peripheral manifestations suggestive of metabolic and endocrine abnormalities. We, therefore, investigated a number of metabolic factors in a 24-hour study of Huntington’s disease gene carriers (premanifest and moderate stage II/III) and controls. Methods Control (n = 15), premanifest (n = 14) and stage II/III (n = 13) participants were studied with blood sampling over a 24-hour period. A battery of clinical tests including neurological rating and function scales were performed. Visceral and subcutaneous adipose distribution was measured using magnetic resonance imaging. We quantified fasting baseline concentrations of glucose, insulin, cholesterol, triglycerides, lipoprotein (a), fatty acids, amino acids, lactate and osteokines. Leptin and ghrelin were quantified in fasting samples and after a standardised meal. We assessed glucose, insulin, growth hormone and cortisol concentrations during a prolonged oral glucose tolerance test. Results We found no highly significant differences in carbohydrate, protein or lipid metabolism markers between healthy controls, premanifest and stage II/III Huntington’s disease subjects. For some markers (osteoprotegerin, tyrosine, lysine, phenylalanine and arginine) there is a suggestion (p values between 0.02 and 0.05) that levels are higher in patients with premanifest HD, but not moderate HD. However, given the large number of statistical tests performed interpretation of these findings must be cautious. Conclusions Contrary to previous studies that showed altered levels of metabolic markers in patients with Huntington’s disease, our study did not demonstrate convincing evidence of abnormalities in any of the markers examined. Our analyses were restricted to Huntington’s disease patients not taking neuroleptics, anti-depressants or other medication affecting metabolic pathways. Even with the modest sample sizes studied, the lack of highly significant results

  10. Metabolic evaluation of stone disease patients: a practical approach.

    PubMed

    Norman, R W

    2001-07-01

    The high success rates of extracorporeal shockwave lithotripsy and endourological techniques, together with their ease of use, in the treatment of urinary stones often overshadow the importance of the metabolic component of stone disease. It is my opinion that the prevention of further stones complements management of the acute episode. This review summarizes a variety of approaches to the measurement and manipulation of individual risk factors in recurrent urinary stone disease.

  11. Assessing the human gut microbiota in metabolic diseases.

    PubMed

    Karlsson, Fredrik; Tremaroli, Valentina; Nielsen, Jens; Bäckhed, Fredrik

    2013-10-01

    Recent findings have demonstrated that the gut microbiome complements our human genome with at least 100-fold more genes. In contrast to our Homo sapiens-derived genes, the microbiome is much more plastic, and its composition changes with age and diet, among other factors. An altered gut microbiota has been associated with several diseases, including obesity and diabetes, but the mechanisms involved remain elusive. Here we discuss factors that affect the gut microbiome, how the gut microbiome may contribute to metabolic diseases, and how to study the gut microbiome. Next-generation sequencing and development of software packages have led to the development of large-scale sequencing efforts to catalog the human microbiome. Furthermore, the use of genetically engineered gnotobiotic mouse models may increase our understanding of mechanisms by which the gut microbiome modulates host metabolism. A combination of classical microbiology, sequencing, and animal experiments may provide further insights into how the gut microbiota affect host metabolism and physiology.

  12. Assessing the Human Gut Microbiota in Metabolic Diseases

    PubMed Central

    Karlsson, Fredrik; Tremaroli, Valentina; Nielsen, Jens; Bäckhed, Fredrik

    2013-01-01

    Recent findings have demonstrated that the gut microbiome complements our human genome with at least 100-fold more genes. In contrast to our Homo sapiens–derived genes, the microbiome is much more plastic, and its composition changes with age and diet, among other factors. An altered gut microbiota has been associated with several diseases, including obesity and diabetes, but the mechanisms involved remain elusive. Here we discuss factors that affect the gut microbiome, how the gut microbiome may contribute to metabolic diseases, and how to study the gut microbiome. Next-generation sequencing and development of software packages have led to the development of large-scale sequencing efforts to catalog the human microbiome. Furthermore, the use of genetically engineered gnotobiotic mouse models may increase our understanding of mechanisms by which the gut microbiome modulates host metabolism. A combination of classical microbiology, sequencing, and animal experiments may provide further insights into how the gut microbiota affect host metabolism and physiology. PMID:24065795

  13. Incident Cardiovascular Disease Events in Metabolically Benign Obese Individuals

    PubMed Central

    Ogorodnikova, Alexandra D.; Kim, Mimi; McGinn, Aileen; Muntner, Paul; Khan, Unab I.; Wildman, Rachel P.

    2012-01-01

    OBJECTIVE While several studies have demonstrated a high prevalence of metabolically benign obesity, little is known about the incidence of cardiovascular disease (CVD) in this group. RESEARCH DESIGN AND METHODS Using pooled data from the Atherosclerosis Risk in Communities and Cardiovascular Health Studies, we assessed the association of metabolically benign obesity with incident CVD (coronary heart disease and stroke) using three existing definitions of metabolically benign obesity: (1) the ATP-III metabolic syndrome definition (≤2 of the ATP-III components, excluding waist), (2) the expanded ATP-III definition (≤1 of: the ATP-III components, HOMA-IR>75th percentile, systemic inflammation [WBC>75th percentile]), and (3) the insulin resistance (IR) based definition (sex-specific lowest quartile of the HOMA-IR distribution among non-diabetic obese). RESULTS The sample included 4,323 normal weight and 6,121 obese individuals. Among obese, 27.0%, 18.1%, and 20.4% were metabolically benign by the three definitions, respectively. CVD incidence among metabolically benign obese defined by the three definitions (mean follow-up 11.8 years) was 8.7%, 7.2%, and 10.3%, respectively, versus 7.9% in low-risk normal weight individuals. Multivariate-adjusted hazard ratios (95% CI) of incident CVD in metabolically benign obese compared to low-risk normal weight individuals were 1.24 (0.99-1.57), 1.16 (0.86-1.56), and 1.28 (1.01-1.62), respectively. CONCLUSIONS Regardless of the definition used, we observed a high prevalence of metabolically benign obesity. All three commonly used definitions were similar in terms of both classification and subsequent risk of CVD, with the expanded ATP-III criteria perhaps identifying the obese group at lowest risk of CVD. PMID:21799477

  14. Calcium metabolism in health and disease.

    PubMed

    Peacock, Munro

    2010-01-01

    This brief review focuses on calcium balance and homeostasis and their relationship to dietary calcium intake and calcium supplementation in healthy subjects and patients with chronic kidney disease and mineral bone disorders (CKD-MBD). Calcium balance refers to the state of the calcium body stores, primarily in bone, which are largely a function of dietary intake, intestinal absorption, renal excretion, and bone remodeling. Bone calcium balance can be positive, neutral, or negative, depending on a number of factors, including growth, aging, and acquired or inherited disorders. Calcium homeostasis refers to the hormonal regulation of serum ionized calcium by parathyroid hormone, 1,25-dihydroxyvitamin D, and serum ionized calcium itself, which together regulate calcium transport at the gut, kidney, and bone. Hypercalcemia and hypocalcemia indicate serious disruption of calcium homeostasis but do not reflect calcium balance on their own. Calcium balance studies have determined the dietary and supplemental calcium requirements needed to optimize bone mass in healthy subjects. However, similar studies are needed in CKD-MBD, which disrupts both calcium balance and homeostasis, because these data in healthy subjects may not be generalizable to this patient group. Importantly, increasing evidence suggests that calcium supplementation may enhance soft tissue calcification and cardiovascular disease in CKD-MBD. Further research is needed to elucidate the risks and mechanisms of soft tissue calcification with calcium supplementation in both healthy subjects and CKD-MBD patients.

  15. Optical diagnosis of a metabolic disease: cystinosis

    NASA Astrophysics Data System (ADS)

    Cinotti, Elisa; Perrot, Jean Luc; Labeille, Bruno; Espinasse, Marine; Ouerdane, Youcef; Boukenter, Aziz; Thuret, Gilles; Gain, Philippe; Campolmi, Nelly; Douchet, Catherine; Cambazard, Frédéric

    2013-04-01

    Nephropathic cystinosis (NC) is a rare autosomal recessive storage disease characterized by the lysosomal accumulation of cystine crystals throughout the body, particularly in blood cells, the cornea, skin, kidneys, the central nervous system, and the muscles. The skin and the cornea are the most accessible sites to explore, and in vivo reflectance confocal microscopy (IVCM) helps identify crystals in both but does not provide any information to help define their composition. Raman spectroscopy (RS) allows cystine to be easily recognized thanks to its characteristic signature with a band at 499 cm-1. Two dermatology confocal microscopes were used to visualize crystals in both the skin and the ocular surface of a cystinosis patient, and an ex vivo Raman examination of a skin biopsy and of the cornea was performed and removed during a corneal graft to confirm the cystine composition of the crystals. Recently, RS has been performed in vivo and coupled with IVCM. In the future, it is suggested that crystals in NC and other deposits in storage diseases could be identified with this noninvasive in vivo technique that combines IVCM to recognize the deposits and RS to confirm their chemical nature.

  16. Metabolic disruption identified in the Huntington's disease transgenic sheep model.

    PubMed

    Handley, Renee R; Reid, Suzanne J; Patassini, Stefano; Rudiger, Skye R; Obolonkin, Vladimir; McLaughlan, Clive J; Jacobsen, Jessie C; Gusella, James F; MacDonald, Marcy E; Waldvogel, Henry J; Bawden, C Simon; Faull, Richard L M; Snell, Russell G

    2016-02-11

    Huntington's disease (HD) is a dominantly inherited, progressive neurodegenerative disorder caused by a CAG repeat expansion within exon 1 of HTT, encoding huntingtin. There are no therapies that can delay the progression of this devastating disease. One feature of HD that may play a critical role in its pathogenesis is metabolic disruption. Consequently, we undertook a comparative study of metabolites in our transgenic sheep model of HD (OVT73). This model does not display overt symptoms of HD but has circadian rhythm alterations and molecular changes characteristic of the early phase disease. Quantitative metabolite profiles were generated from the motor cortex, hippocampus, cerebellum and liver tissue of 5 year old transgenic sheep and matched controls by gas chromatography-mass spectrometry. Differentially abundant metabolites were evident in the cerebellum and liver. There was striking tissue-specificity, with predominantly amino acids affected in the transgenic cerebellum and fatty acids in the transgenic liver, which together may indicate a hyper-metabolic state. Furthermore, there were more strong pair-wise correlations of metabolite abundance in transgenic than in wild-type cerebellum and liver, suggesting altered metabolic constraints. Together these differences indicate a metabolic disruption in the sheep model of HD and could provide insight into the presymptomatic human disease.

  17. Metabolic disruption identified in the Huntington's disease transgenic sheep model.

    PubMed

    Handley, Renee R; Reid, Suzanne J; Patassini, Stefano; Rudiger, Skye R; Obolonkin, Vladimir; McLaughlan, Clive J; Jacobsen, Jessie C; Gusella, James F; MacDonald, Marcy E; Waldvogel, Henry J; Bawden, C Simon; Faull, Richard L M; Snell, Russell G

    2016-01-01

    Huntington's disease (HD) is a dominantly inherited, progressive neurodegenerative disorder caused by a CAG repeat expansion within exon 1 of HTT, encoding huntingtin. There are no therapies that can delay the progression of this devastating disease. One feature of HD that may play a critical role in its pathogenesis is metabolic disruption. Consequently, we undertook a comparative study of metabolites in our transgenic sheep model of HD (OVT73). This model does not display overt symptoms of HD but has circadian rhythm alterations and molecular changes characteristic of the early phase disease. Quantitative metabolite profiles were generated from the motor cortex, hippocampus, cerebellum and liver tissue of 5 year old transgenic sheep and matched controls by gas chromatography-mass spectrometry. Differentially abundant metabolites were evident in the cerebellum and liver. There was striking tissue-specificity, with predominantly amino acids affected in the transgenic cerebellum and fatty acids in the transgenic liver, which together may indicate a hyper-metabolic state. Furthermore, there were more strong pair-wise correlations of metabolite abundance in transgenic than in wild-type cerebellum and liver, suggesting altered metabolic constraints. Together these differences indicate a metabolic disruption in the sheep model of HD and could provide insight into the presymptomatic human disease. PMID:26864449

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

    PubMed

    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

  19. Cyclooxygenase-derived vasoconstriction restrains hypoxia-mediated cerebral vasodilation in young adults with metabolic syndrome

    PubMed Central

    Harrell, John W.

    2013-01-01

    Poor cerebrovascular function in metabolic syndrome (MetSyn) likely contributes to elevated risk of cerebrovascular disease in this growing clinical population. Younger MetSyn adults without clinical evidence of cerebrovascular disease exhibit preserved hypercapnic vasodilation yet markedly impaired hypoxic vasodilation, but the mechanisms behind reduced hypoxic vasodilation are unknown. Based on data from rats, we tested the hypothesis that younger adults with MetSyn exhibit reduced cerebral hypoxic vasodilation due to loss of vasodilating prostaglandins. Middle cerebral artery velocity (MCAv) was measured with transcranial Doppler ultrasound in adults with MetSyn (n = 13, 33 ± 3 yr) and healthy controls (n = 15, 31 ± 2 yr). Isocapnic hypoxia was induced by titrating inspired oxygen to lower arterial saturation to 90% and 80% for 5 min each. Separately, hypercapnia was induced by increasing end-tidal CO2 10 mmHg above baseline levels. Cyclooxygenase inhibition (100 mg indomethacin) was conducted in a randomized double-blind, placebo controlled design. MCAv was normalized for group differences in blood pressure (healthy: 89 ± 2 mmHg vs. MetSyn: 102 ± 2 mmHg) as cerebrovascular conductance index (CVCi), and used to assess cerebral vasodilation. Hypoxia increased CVCi in both groups; however, vasodilation was ∼55% lower in MetSyn at SpO2 = 80% (P < 0.05). Indomethacin tended to decrease hypoxic vasodilation in healthy controls, and unexpectedly increased dilation in MetSyn (P < 0.05). In contrast to hypoxia, hypercapnia-mediated vasodilation was similar between groups, as was the decrease in vasodilation with indomethacin. These data indicate increased production of vasoconstrictor prostaglandins restrains hypoxic cerebral vasodilation in MetSyn, preventing them from responding appropriately to this important physiological stressor. PMID:24213610

  20. Relationships between metabolic rate, muscle electromyograms, and swim performance of adult chinook salmon

    SciTech Connect

    Geist, David R. ); Brown, Richard S. ); Cullinan, Valerie I. ); Mesa, Matthew G.; VanderKooi, S P.; McKinstry, Craig A. )

    2003-10-01

    We measured oxygen consumption rates of adult spring Chinook salmon and compared these values to other species of Pacific salmon. Our results indicated that adult salmon achieve their maximum level of oxygen consumption at about their upper critical swim speed. It is also at this speed that the majority of the energy supplied to the swimming fish switches from red muscle (powered by aerobic metabolism) to white muscle (powered by anaerobic metabolism). Determining the swimming performance of adult salmon will assist managers in developing fishways and other means to safely pass fish over hydroelectric dams and other man-made structures.

  1. The impact of metabolic disease associated with metabolic syndrome on human pregnancy.

    PubMed

    Malek, Antoine

    2014-01-01

    Metabolic diseases induced by metabolic syndrome (MS) have been increased during the past two decades. During healthy pregnancy maternal organs and placenta are challenged to adapt to the increasingly physiological changes. In addition to the increasingly proatherogenic MS, pregnant woman develops a high cardiac output, hypercoagulability, increased inflammatory activity and insulin resistance with dyslipidemia. The MS describes a cluster of metabolic changes associated with an impact on the physiology of many organs. While the metabolic syndrome is directly responsible for the development of atherosclerotic cardiovascular disease, additional impact on human pregnancy like preterm delivery with low-birth-weight infants as well as the development of diseases such as diabetes, preeclampsia and hypertension. Recent evidence suggests that MS is originated in fetal life in association with maternal nutrition during pregnancy and fetal programming which apparently increases the susceptibility for MS in children and later life. This review will describe the MS in association with the origin of the emerging diseases during pregnancy such as diabetes, preeclampsia and others. The influence of perinatal environment and maternal diet and smoking on MS as well as the genetic biomarkers of MS will be described.

  2. Larval starvation improves metabolic response to adult starvation in honey bees (Apis mellifera L.).

    PubMed

    Wang, Ying; Campbell, Jacob B; Kaftanoglu, Osman; Page, Robert E; Amdam, Gro V; Harrison, Jon F

    2016-04-01

    Environmental changes during development have long-term effects on adult phenotypes in diverse organisms. Some of the effects play important roles in helping organisms adapt to different environments, such as insect polymorphism. Others, especially those resulting from an adverse developmental environment, have a negative effect on adult health and fitness. However, recent studies have shown that those phenotypes influenced by early environmental adversity have adaptive value under certain (anticipatory) conditions that are similar to the developmental environment, though evidence is mostly from morphological and behavioral observations and it is still rare at physiological and molecular levels. In the companion study, we applied a short-term starvation treatment to fifth instar honey bee larvae and measured changes in adult morphology, starvation resistance, hormonal and metabolic physiology and gene expression. Our results suggest that honey bees can adaptively respond to the predicted nutritional stress. In the present study, we further hypothesized that developmental starvation specifically improves the metabolic response of adult bees to starvation instead of globally affecting metabolism under well-fed conditions. Here, we produced adult honey bees that had experienced a short-term larval starvation, then we starved them for 12 h and monitored metabolic rate, blood sugar concentrations and metabolic reserves. We found that the bees that experienced larval starvation were able to shift to other fuels faster and better maintain stable blood sugar levels during starvation. However, developmental nutritional stress did not change metabolic rates or blood sugar levels in adult bees under normal conditions. Overall, our study provides further evidence that early larval starvation specifically improves the metabolic responses to adult starvation in honey bees. PMID:27030776

  3. Larval starvation improves metabolic response to adult starvation in honey bees (Apis mellifera L.).

    PubMed

    Wang, Ying; Campbell, Jacob B; Kaftanoglu, Osman; Page, Robert E; Amdam, Gro V; Harrison, Jon F

    2016-04-01

    Environmental changes during development have long-term effects on adult phenotypes in diverse organisms. Some of the effects play important roles in helping organisms adapt to different environments, such as insect polymorphism. Others, especially those resulting from an adverse developmental environment, have a negative effect on adult health and fitness. However, recent studies have shown that those phenotypes influenced by early environmental adversity have adaptive value under certain (anticipatory) conditions that are similar to the developmental environment, though evidence is mostly from morphological and behavioral observations and it is still rare at physiological and molecular levels. In the companion study, we applied a short-term starvation treatment to fifth instar honey bee larvae and measured changes in adult morphology, starvation resistance, hormonal and metabolic physiology and gene expression. Our results suggest that honey bees can adaptively respond to the predicted nutritional stress. In the present study, we further hypothesized that developmental starvation specifically improves the metabolic response of adult bees to starvation instead of globally affecting metabolism under well-fed conditions. Here, we produced adult honey bees that had experienced a short-term larval starvation, then we starved them for 12 h and monitored metabolic rate, blood sugar concentrations and metabolic reserves. We found that the bees that experienced larval starvation were able to shift to other fuels faster and better maintain stable blood sugar levels during starvation. However, developmental nutritional stress did not change metabolic rates or blood sugar levels in adult bees under normal conditions. Overall, our study provides further evidence that early larval starvation specifically improves the metabolic responses to adult starvation in honey bees.

  4. Individual limb work does not explain the greater metabolic cost of walking in elderly adults.

    PubMed

    Ortega, Justus D; Farley, Claire T

    2007-06-01

    Elderly adults consume more metabolic energy during walking than young adults. Our study tested the hypothesis that elderly adults consume more metabolic energy during walking than young adults because they perform more individual limb work on the center of mass. Thus we compared how much individual limb work young and elderly adults performed on the center of mass during walking. We measured metabolic rate and ground reaction force while 10 elderly and 10 young subjects walked at 5 speeds between 0.7 and 1.8 m/s. Compared with young subjects, elderly subjects consumed an average of 20% more metabolic energy (P=0.010), whereas they performed an average of 10% less individual limb work during walking over the range of speeds (P=0.028). During the single-support phase, elderly and young subjects both conserved approximately 80% of the center of mass mechanical energy by inverted pendulum energy exchange and performed a similar amount of individual limb work (P=0.473). However, during double support, elderly subjects performed an average of 17% less individual limb work than young subjects (P=0.007) because their forward speed fluctuated less (P=0.006). We conclude that the greater metabolic cost of walking in elderly adults cannot be explained by a difference in individual limb work. Future studies should examine whether a greater metabolic cost of stabilization, reduced muscle efficiency, greater antagonist cocontraction, and/or a greater cost of generating muscle force cause the elevated metabolic cost of walking in elderly adults. PMID:17363623

  5. Endothelial cell metabolism in normal and diseased vasculature

    PubMed Central

    Eelen, Guy; de Zeeuw, Pauline; Simons, Michael; Carmeliet, Peter

    2015-01-01

    Higher organisms rely on a closed cardiovascular circulatory system with blood vessels supplying vital nutrients and oxygen to distant tissues. Not surprisingly, vascular pathologies rank among the most life-threatening diseases. At the crux of most of these vascular pathologies are (dysfunctional) endothelial cells (ECs), the cells lining the blood vessel lumen. ECs display the remarkable capability to switch rapidly from a quiescent state to a highly migratory and proliferative state during vessel sprouting. This angiogenic switch has long been considered to be dictated by angiogenic growth factors (eg vascular endothelial growth factor; VEGF) and other signals (eg Notch) alone, but recent findings show that it is also driven by a metabolic switch in ECs. Furthermore, these changes in metabolism may even override signals inducing vessel sprouting. Here, we review how EC metabolism differs between the normal and dysfunctional/diseased vasculature and how it relates to or impacts the metabolism of other cell types contributing to the pathology. We focus on the biology of ECs in tumor blood vessel and diabetic ECs in atherosclerosis as examples of the role of endothelial metabolism in key pathological processes. Finally, current as well as unexplored ‘EC metabolism’-centric therapeutic avenues are discussed. PMID:25814684

  6. Dietary inorganic nitrate: From villain to hero in metabolic disease?

    PubMed Central

    McNally, Ben; Griffin, Julian L.

    2015-01-01

    Historically, inorganic nitrate was believed to be an inert by‐product of nitric oxide (NO) metabolism that was readily excreted by the body. Studies utilising doses of nitrate far in excess of dietary and physiological sources reported potentially toxic and carcinogenic effects of the anion. However, nitrate is a significant component of our diets, with the majority of the anion coming from green leafy vegetables, which have been consistently shown to offer protection against obesity, type 2 diabetes and metabolic diseases. The discovery of a metabolic pathway in mammals, in which nitrate is reduced to NO, via nitrite, has warranted a re‐examination of the physiological role of this small molecule. Obesity, type 2 diabetes and the metabolic syndrome are associated with a decrease in NO bioavailability. Recent research suggests that the nitrate‐nitrite‐NO pathway may be harnessed as a therapeutic to supplement circulating NO concentrations, with both anti‐obesity and anti‐diabetic effects, as well as improving vascular function. In this review, we examine the key studies that have led to the re‐evaluation of the physiological function of inorganic nitrate, from toxic and carcinogenic metabolite, to a potentially important and beneficial agent in the treatment of metabolic disease. PMID:26227946

  7. Dietary inorganic nitrate: From villain to hero in metabolic disease?

    PubMed

    McNally, Ben; Griffin, Julian L; Roberts, Lee D

    2016-01-01

    Historically, inorganic nitrate was believed to be an inert by-product of nitric oxide (NO) metabolism that was readily excreted by the body. Studies utilising doses of nitrate far in excess of dietary and physiological sources reported potentially toxic and carcinogenic effects of the anion. However, nitrate is a significant component of our diets, with the majority of the anion coming from green leafy vegetables, which have been consistently shown to offer protection against obesity, type 2 diabetes and metabolic diseases. The discovery of a metabolic pathway in mammals, in which nitrate is reduced to NO, via nitrite, has warranted a re-examination of the physiological role of this small molecule. Obesity, type 2 diabetes and the metabolic syndrome are associated with a decrease in NO bioavailability. Recent research suggests that the nitrate-nitrite-NO pathway may be harnessed as a therapeutic to supplement circulating NO concentrations, with both anti-obesity and anti-diabetic effects, as well as improving vascular function. In this review, we examine the key studies that have led to the re-evaluation of the physiological function of inorganic nitrate, from toxic and carcinogenic metabolite, to a potentially important and beneficial agent in the treatment of metabolic disease.

  8. Phytanic acid metabolism in health and disease.

    PubMed

    Wanders, Ronald J A; Komen, Jasper; Ferdinandusse, Sacha

    2011-09-01

    Phytanic acid (3,7,11,15-tetramethylhexadecanoic acid) is a branched-chain fatty acid which cannot be beta-oxidized due to the presence of the first methyl group at the 3-position. Instead, phytanic acid undergoes alpha-oxidation to produce pristanic acid (2,6,10,14-tetramethylpentadecanoic acid) plus CO(2). Pristanic acid is a 2-methyl branched-chain fatty acid which can undergo beta-oxidation via sequential cycles of beta-oxidation in peroxisomes and mitochondria. The mechanism of alpha-oxidation has been resolved in recent years as reviewed in this paper, although some of the individual enzymatic steps remain to be identified. Furthermore, much has been learned in recent years about the permeability properties of the peroxisomal membrane with important consequences for the alpha-oxidation process. Finally, we present new data on the omega-oxidation of phytanic acid making use of a recently generated mouse model for Refsum disease in which the gene encoding phytanoyl-CoA 2-hydroxylase has been disrupted.

  9. Tree nut consumption is associated with better adiposity measures and cardiovascular and metabolic syndrome health risk factors in U.S adults: NHANES 2005-2010

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Previous research has shown inconsistencies in the association of tree nut consumption with risk factors for cardiovascular disease (CVD) and metabolic syndrome (MetS). To determine the association of tree nut consumption with risk factors for CVD and for MetS in adults. NHANES 2005-2010 data were u...

  10. Factor analysis of modifiable cardiovascular risk factors and prevalence of metabolic syndrome in adult Taiwanese.

    PubMed

    Tsai, Chung-Huang; Li, Tsai-Chung; Lin, Cheng-Chieh; Tsay, Hsin-Sheng

    2011-10-01

    To assess the clustering of modifiable cardiovascular risk factors among Taiwanese adults, we evaluated 579 healthy participants who underwent health examinations between May and December 2007. Exploratory factor analysis was used to examine risk factor clustering. Smoking, alcohol intake, exercise habits, body mass index, waist circumference, total cholesterol, triglycerides, high- and low-density lipoprotein cholesterol, fasting glucose, uric acid, serum hepatic enzymes, and mean arterial pressure were assessed. Separate factor analyses assessed total and low-density lipoprotein cholesterol. Principal components analysis identified five factors for a model without low-density lipoprotein cholesterol and four factors for a model without total cholesterol. Four common factors in both models explained between 51.1 and 51.8% of variance in the original 14 factors. Metabolic factors, hematological factors (white blood cells and platelets), lifestyle factors (smoking and alcohol consumption), and exercise habits and fasting blood glucose explained about 20, 11, 10, 10% of total variance, respectively. In the model without low-density lipoprotein cholesterol, total cholesterol factor explained 8.83% of variance. This study confirmed clustering of established metabolic syndrome components and revealed additional associated cardiovascular disease risk factors, including lifestyle factors, exercise and total cholesterol, which should be targeted in prevention efforts.

  11. Exosomes as the source of biomarkers of metabolic diseases

    PubMed Central

    Lee, Min-Jae; Park, Dong-Ho

    2016-01-01

    Exosomes are extracellular vesicles that contain molecules that regulate the metabolic functions of adjacent or remote cells. Recent in vitro, in vivo and clinical studies support the hypothesis that exosomes released from various cell types play roles in the progression of metabolic disorders including type 2 diabetes. Based on this concept and advances in other diseases, the proteins, mRNA, microRNA and lipids in exosomes isolated from biological fluids have been proposed as biomarkers in metabolic disorders. However, several problems with the development of clinically applicable biomarkers have not been resolved. In this review, the biologic functions of exosomes are briefly introduced, and we discuss the technical and practical pros and cons of different methods of exosome isolation for the identification of exosomal biomarkers of metabolic disorders. Standardization of preanalytical variables and isolation of high-purity exosomes from fully characterized biological fluids will be necessary for the identification of useful exosomal biomarkers that can provide insights into the pathogenic mechanisms of complications of metabolic syndrome and of whole-body metabolism. PMID:27777903

  12. The genetic basis of kidney cancer: a metabolic disease

    PubMed Central

    Linehan, W. Marston; Srinivasan, Ramaprasad; Schmidt, Laura S.

    2010-01-01

    Kidney cancer is not a single disease but encompasses a number of different types of cancer that occur in the kidney, each caused by a different gene with a different histology and clinical course that responds differently to therapy. Each of the seven known kidney cancer genes, VHL, MET, FLCN, TSC1, TSC2, FH and SDH, is involved in pathways that respond to metabolic stress and/or nutrient stimulation. The VHL protein is a component of the oxygen and iron sensing pathway that regulates HIF levels in the cell. HGF/MET signaling affects the LKB1/AMPK energy sensing cascade. The FLCN/FNIP1/FNIP2 complex binds AMPK and therefore may interact with the cellular energy and nutrient sensing pathways, AMPK-TSC1/2-mTOR and PI3K-Akt-mTOR. TSC1/TSC2 are downstream of AMPK and negatively regulate mTOR in response to cellular energy deficit. FH and SDH play a central role in the mitochondrial tricarboxylic acid (TCA) cycle whose activities are coupled to energy production through oxidative phosphorylation. Mutations in each of these kidney cancer genes result in dysregulation of metabolic pathways involved in oxygen, iron, energy and/or nutrient sensing suggesting that kidney cancer is a disease of cell metabolism. Targeting the fundamental metabolic abnormalities in kidney cancer provides a unique opportunity for the development of more effective forms of therapy for this disease. PMID:20448661

  13. Ulcer Disease, Metabolic Alkalosis and Hyperparathyroidism: A Mechanism of Interrelationship?

    PubMed Central

    Kaplan, Edwin L.; Peskin, Gerald W.; Deveney, Clifford; Way, Lawrence; Jaffe, Bernard

    1974-01-01

    In both normal volunteers and in patients with primary hyperparathyroidism, the induction of a metabolic alkalosis by infusion of sodium bicarbonate results in a decrease in serum calcium ion and in an increase of circulating parathyroid hormone concentrations. Bicarbonate infusion may serve in man as a new provocative test for release of parathyroid hormone. Furthermore, we speculate that the metabolic alkalosis which is found at times in patients with the Zollinger-Ellison syndrome and severe peptic ulcer disease may result in parathyroid gland stimulation. PMID:4416767

  14. Modeling metabolic homeostasis and nutrient sensing in Drosophila: implications for aging and metabolic diseases

    PubMed Central

    Owusu-Ansah, Edward; Perrimon, Norbert

    2014-01-01

    Over the past decade, numerous reports have underscored the similarities between the metabolism of Drosophila and vertebrates, with the identification of evolutionarily conserved enzymes and analogous organs that regulate carbohydrate and lipid metabolism. It is now well established that the major metabolic, energy-sensing and endocrine signaling networks of vertebrate systems are also conserved in flies. Accordingly, studies in Drosophila are beginning to unravel how perturbed energy balance impinges on lifespan and on the ensuing diseases when energy homeostasis goes awry. Here, we highlight several emerging concepts that are at the nexus between obesity, nutrient sensing, metabolic homeostasis and aging. Specifically, we summarize the endocrine mechanisms that regulate carbohydrate and lipid metabolism, and provide an overview of the neuropeptides that regulate feeding behavior. We further describe the various efforts at modeling the effects of high-fat or -sugar diets in Drosophila and the signaling mechanisms involved in integrating organ function. Finally, we draw attention to some of the cardinal discoveries made with these disease models and how these could spur new research questions in vertebrate systems. PMID:24609035

  15. Relation of components of the metabolic syndrome to left ventricular geometry in hispanic and non-hispanic black adults

    PubMed Central

    Apridonidze, Teimuraz; Shaqra, Hussein; Ktaich, Nessrine; Liu, Jennifer E; Bella, Jonathan N

    2011-01-01

    Background: Left ventricular (LV) hypertrophy is an independent predictor of increased cardiovascular morbidity and mortality. It remains unclear whether components of the metabolic syndrome are associated with LV hypertrophy. Methods and Results: Accordingly, we analyzed echocardiograms in 192 consecutive ambulatory patients referred for echocardiography from October to December 2004. Patients were excluded if they had atrial fibrillation, significant valvular heart disease or failed to cooperate for echocardiogram. Of these, 126 (66%) patients met Adult Treatment Panel (ATP) III diagnostic criteria for the metabolic syndrome. 29% had any 3 metabolic syndrome components, 18% had any 4 metabolic syndrome components and 17% had all 5 metabolic syndrome components. In analyses of variance adjusted for age and sex, LV mass and LV mass adjusted to its allometric relation to height2.7 (LV mass/height2.7) were higher in patients with metabolic syndrome compared to those without metabolic syndrome (237 g [228-239 95%CI] vs. 224 g [206-239 95%CI] p=0.005 and 62 g/m2.7 [59-65 95%CI] vs. 56 g/m2.7 [52-60 95%CI] p=0.014, respectively). The prevalence of LV hypertrophy using prognostically-validated gender-specific partition values for LV mass/height2.7 was significantly higher in metabolic syndrome patients than in those without metabolic syndrome (81 v. 58%, p<0.001). There was a step-wise increase in LV mass/height2.7 in those with no metabolic syndrome components to those with increasing number of metabolic syndrome components (Figure, p<0.001). In this study of high-risk patients, the significant independent predictors of LV hypertrophy were only high blood pressure (OR=3.2, p=0.008) and increased waist circumference (OR=2.8, p=0.006) with no interaction between blood pressure and waist circumference. Conclusion: Metabolic syndrome is associated with higher LV mass and prevalence of LV hypertrophy. Increasing number of metabolic syndrome components is associated with step

  16. Adult obesity, disease and longevity in Mexico

    PubMed Central

    Palloni, Alberto; Beltrán-Sánchez, Hiram; Novak, Beatriz; Pinto, Guido; Wong, Rebeca

    2015-01-01

    Objective To obtain estimates of the effects of overweight and obesity on the incidence of type 2 diabetes (T2D) and adult mortality. Materials and methods We use three waves (2000, 2002, 2012) of the Mexican Health and Aging Survey (MHAS). We employ parametric hazard models to estimate mortality and conventional logistic models to estimate incidence of T2D. Results Obesity and overweight have a strong effect on the incidence of T2D; this, combined with the large impact of diabetes on adult mortality, generates increases in mortality that translate into losses of 2 to 3 years of life expectancy at age 50. Conclusions If increasing trends in obesity in Mexico continue as in the past, progress in adult survival may be slowed down considerably and the incidence of T2D will continue to increase. PMID:26172231

  17. Altered response to neuroendocrine challenge linked to indices of the metabolic syndrome in healthy adults.

    PubMed

    Tyrka, A R; Walters, O C; Price, L H; Anderson, G M; Carpenter, L L

    2012-06-01

    Metabolic syndrome (MetS) is characterized by central obesity, hypertension, insulin resistance, and hypercholesterolemia. Hypothalamic-pituitary-adrenal (HPA) axis activity is frequently abnormal in MetS, and excessive cortisol exposure may be implicated in metabolic derangements. We investigated the hypothesis that cortisol and adrenocorticotropic hormone (ACTH) responses to a standardized neuroendocrine challenge test would be associated with indices of MetS in a community sample of healthy adults. Healthy adults, 125 men and 170 women, without significant medical problems or chronic medications were recruited from the community. Participants completed the dexamethasone/corticotropin-releasing hormone (Dex/CRH) test, and anthropometric measurements, blood pressure, glycosylated hemoglobin (HbA1c), and cholesterol were measured. Participants reported on their history of early life stress and recent stress, as well as mood and anxiety symptoms. Cortisol and ACTH responses to the Dex/CRH test were negatively associated with measures of central adiposity (p<0.001) and blood pressure (p<0.01), and positively associated with HDL cholesterol (p<0.01). These findings remained significant after controlling for body mass index (BMI). Measures of stress and anxiety and depressive symptoms were negatively correlated with cortisol and ACTH responses in the Dex/CRH test but were not related to MetS indices. That altered HPA axis function is linked to MetS components even in a healthy community sample suggests that these processes may be involved in the pathogenesis of MetS. Identification of premorbid risk processes might allow for detection and intervention prior to the development of disease. PMID:22549400

  18. Cortical metabolism, acetylcholinesterase staining and pathological changes in Alzheimer's disease.

    PubMed

    McGeer, E G; McGeer, P L; Kamo, H; Tago, H; Harrop, R

    1986-11-01

    The local cerebral metabolic rate for glucose (LCMRgl) was determined by positron emission tomography (PET) using the 18F-fluorodeoxyglucose method in a series of Alzheimer patients and normal controls. The LCMRgl declined in the cerebral cortex with age, but the decrement was significantly greater in the clinically diagnosed Alzheimer's cases. Comparison of PET and psychological data indicated that, as the disease progressed clinically, the reduction in cortical LCMRgl and the number of cortical regions involved also increased. Variable regions of cortex were involved in the early stages but the temporal, parietal and frontal regions were most typically affected. One case coming to autopsy showed that the severity of the LCMRgl decline paralleled loss of neurons in the cortex and their replacement with astroglia. A case of Pick's disease coming to autopsy had shown a different and highly characteristic pattern of cortical metabolic defect. In this case also a poor metabolic rate was associated with extensive gliosis. Acetylcholinesterase (AChE) staining of the cerebral cortex in elderly normals and Alzheimer's disease cases with a new, highly sensitive method showed that in Alzheimer's disease there was an extensive loss of AChE-positive fibers with senile plaques frequently incorporating AChE-positive fiber debris. AChE staining of the substantia innominata area, where the cells giving rise to these neocortical fibers are presumably located, also showed evidence of degenerating cells and fibers.

  19. Cerebellar Disease in an Adult Cow

    PubMed Central

    Oz, H. H.; Nicholson, S. S.; Al-Bagdadi, F. K.; Zeman, D. H.

    1986-01-01

    This is the report of clinical signs and lesions of a cerebellar disorder in an adult four year old Limousin cow grazing perennial ryegrass (Lolium perenne). The most striking histopathological lesion was a marked paucity of Purkinje cells throughout the cerebellum. ImagesFigure 1.Figure 2. PMID:17422607

  20. Early Origins of Adult Disease: Approaches for Investigating the Programmable Epigenome in Humans, Nonhuman Primates, and Rodents

    PubMed Central

    Ganu, Radhika S.; Harris, R. Alan; Collins, Kiara; Aagaard, Kjersti M.

    2012-01-01

    According to the developmental origins of health and disease hypothesis, in utero experiences reprogram an individual for immediate adaptation to gestational perturbations, with the sequelae of later-in-life risk of metabolic disease. An altered gestational milieu with resultant adult metabolic disease has been observed in instances of both in utero constraint (e.g., from famine or uteroplacental insufficiency) and overt caloric abundance (e.g., from a maternal high-fat, caloric-dense diet). The commonality of the adult metabolic phenotype begs the question of how diverse in utero experiences (i.e., reprogramming events) converge on common metabolic pathways and how the memory of these events is maintained across the lifespan. We and others have investigated the molecular mechanisms underlying fetal programming and observed that epigenetic modifications to the fetal and placental epigenome accompany these reprogramming events. Based on several lines of emerging data in human and nonhuman primates, it is now felt that modified epigenetic signature—and the histone code in particular—underlies alterations in postnatal gene expression and metabolic pathways central to accurate functioning and maintenance of health. Because of the tissue lineage specificity of many of these modifications, nonhuman primates serve as an apt model system for the capacity to recapitulate human gene expression and regulation during development. This review summarizes recent epigenetic advances using rodent and primate (both human and nonhuman) models during in utero development and contributing to adult diseases later in life. PMID:23744969

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

    PubMed

    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

  2. Microvesicles/exosomes as potential novel biomarkers of metabolic diseases

    PubMed Central

    Müller, Günter

    2012-01-01

    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 complete individual pathogenetic pathways underlying metabolic diseases. A critical step in further validation of EMVs as biomarkers will rely on

  3. Nutrition for Early Chronic Kidney Disease in Adults

    MedlinePlus

    ... Information Center Medical Education Institute, Inc. (MEI) MedlinePlus Kidney and Urologic Disease Organizations Many organizations provide support ... KB)​​​​​ Alternate Language URL Nutrition for Early Chronic Kidney Disease in Adults Page Content On this page: ...

  4. Metabolic Syndrome and Periodontal Disease Progression in Men.

    PubMed

    Kaye, E K; Chen, N; Cabral, H J; Vokonas, P; Garcia, R I

    2016-07-01

    Metabolic syndrome, a cluster of 3 or more risk factors for cardiovascular disease, is associated with periodontal disease, but few studies have been prospective in design. This study's aim was to determine whether metabolic syndrome predicts tooth loss and worsening of periodontal disease in a cohort of 760 men in the Department of Veterans Affairs Dental Longitudinal Study and Normative Aging Study who were followed up to 33 y from 1981 to 2013. Systolic and diastolic blood pressures were measured with a standard mercury sphygmomanometer. Waist circumference was measured in units of 0.1 cm following a normal expiration. Fasting blood samples were measured in duplicate for glucose, triglyceride, and high-density lipoprotein. Calibrated periodontists served as dental examiners. Periodontal outcome events on each tooth were defined as progression to predefined threshold levels of probing pocket depth (≥5 mm), clinical attachment loss (≥5 mm), mobility (≥0.5 mm), and alveolar bone loss (≥40% of the distance from the cementoenamel junction to the root apex, on radiographs). Hazards ratios (95% confidence intervals) of tooth loss or a periodontitis event were estimated from tooth-level extended Cox proportional hazards regression models that accounted for clustering of teeth within individuals and used time-dependent status of metabolic syndrome. Covariates included age, education, smoking status, plaque level, and initial level of the appropriate periodontal disease measure. Metabolic syndrome as defined by the International Diabetes Federation increased the hazards of tooth loss (1.39; 1.08 to 1.79), pocket depth ≥5 mm (1.37; 1.14 to 1.65), clinical attachment loss ≥5 mm (1.19; 1.00 to 1.41), alveolar bone loss ≥40% (1.25; 1.00 to 1.56), and tooth mobility ≥0.5 mm (1.43; 1.07 to 1.89). The number of positive metabolic syndrome conditions was also associated with each of these outcomes. These findings suggest that the metabolic disturbances that

  5. Influence of metabolic syndrome on upper gastrointestinal disease.

    PubMed

    Sogabe, Masahiro; Okahisa, Toshiya; Kimura, Tetsuo; Okamoto, Koichi; Miyamoto, Hiroshi; Muguruma, Naoki; Takayama, Tetsuji

    2016-08-01

    A recent increase in the rate of obesity as a result of insufficient physical exercise and excess food consumption has been seen in both developed and developing countries throughout the world. Additionally, the recent increased number of obese individuals with lifestyle-related diseases associated with abnormalities in glucose metabolism, dyslipidemia, and hypertension, defined as metabolic syndrome (MS), has been problematic. Although MS has been highlighted as a risk factor for ischemic heart disease and arteriosclerotic diseases, it was also recently shown to be associated with digestive system disorders, including upper gastrointestinal diseases. Unlike high body weight and high body mass index, abdominal obesity with visceral fat accumulation is implicated in the onset of various digestive system diseases because excessive visceral fat accumulation may cause an increase in intra-abdominal pressure, inducing the release of various bioactive substances, known as adipocytokines, including tumor necrosis factor-α, interleukin-6, resistin, leptin, and adiponectin. This review article focuses on upper gastrointestinal disorders and their association with MS, including obesity, visceral fat accumulation, and the major upper gastrointestinal diseases. PMID:27372302

  6. Mechanistic modeling of aberrant energy metabolism in human disease

    PubMed Central

    Sangar, Vineet; Eddy, James A.; Simeonidis, Evangelos; Price, Nathan D.

    2012-01-01

    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 (CB) 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. PMID:23112774

  7. Peroxisome proliferator-activated receptors, metabolic syndrome and cardiovascular disease.

    PubMed

    Azhar, Salman

    2010-09-01

    Metabolic syndrome (MetS) is a constellation of risk factors including insulin resistance, central obesity, dyslipidemia and hypertension that markedly increase the risk of Type 2 diabetes (T2DM) and cardiovascular disease (CVD). The peroxisome proliferators-activated receptor (PPAR) isotypes, PPARα, PPARδ/ß and PPARγ are ligand-activated nuclear transcription factors, which modulate the expression of an array of genes that play a central role in regulating glucose, lipid and cholesterol metabolism, where imbalance can lead to obesity, T2DM and CVD. They are also drug targets, and currently, PPARα (fibrates) and PPARγ (thiazolodinediones) agonists are in clinical use for treating dyslipidemia and T2DM, respectively. These metabolic characteristics of the PPARs, coupled with their involvement in metabolic diseases, mean extensive efforts are underway worldwide to develop new and efficacious PPAR-based therapies for the treatment of additional maladies associated with the MetS. This article presents an overview of the functional characteristics of three PPAR isotypes, discusses recent advances in our understanding of the diverse biological actions of PPARs, particularly in the vascular system, and summarizes the developmental status of new single, dual, pan (multiple) and partial PPAR agonists for the clinical management of key components of MetS, T2DM and CVD. It also summarizes the clinical outcomes from various clinical trials aimed at evaluating the atheroprotective actions of currently used fibrates and thiazolodinediones. PMID:20932114

  8. Evaluation of fasts for investigating hypoglycaemia or suspected metabolic disease.

    PubMed Central

    Morris, A A; Thekekara, A; Wilks, Z; Clayton, P T; Leonard, J V; Aynsley-Green, A

    1996-01-01

    AIM--To assess the value and safety of fasts for investigating hypoglycaemia or suspected metabolic disease. STUDY DESIGN--Review of all diagnostic fasts performed over a 2.5 year period. SETTING--The neonatal intensive care unit and programmed investigation unit at a tertiary referral centre for endocrinology and metabolic disease. RESULTS--138 diagnostic fasts were performed during the study period. Hypoglycaemia (< 2.6 mmol/l) occurred in 54 cases but in only four did the blood glucose concentration fall below 1.5 mmol/l. One patient became unwell as a result of a fast, but prompt treatment averted any sequelae. Specific endocrine or metabolic defects were identified in 30 cases, the most common being hyperinsulinism and beta-oxidation defects. CONCLUSIONS--Fasting is safe if conducted on an experienced unit with appropriate guidelines. It continues to provide useful information for diagnosis and management, particularly in cases of hyperinsulinism. Diagnoses should, however, be established by lower risk procedures whenever possible. Thus specimens for metabolic and endocrine studies should be obtained during the presenting episode and blood acylcarnitine species should be analysed prior to fasting. PMID:8869190

  9. Metabolic Heritability at Birth: Implications for Chronic Disease Research

    PubMed Central

    Ryckman, Kelli K.; Smith, Caitlin J.; Jelliffe-Pawlowski, Laura L; Momany, Allison M.; Berberich, Stanton L.; Murray, Jeffrey C.

    2014-01-01

    Recent genome-wide association studies of the adult human metabolome have identified genetic variants associated with relative levels of several acylcarnitines, which are important clinical correlates for chronic conditions such as type 2 diabetes and obesity. We have previously shown that these same metabolite levels are highly heritable at birth; however, no studies to our knowledge have examined genetic associations with these metabolites measured at birth. Here, we examine, in 743 newborns, 58 single nucleotide polymorphisms (SNPs) in 11 candidate genes previously associated with differing relative levels of short-chain acylcarnitines in adults. Six SNPs (rs2066938, rs3916, rs3794215, rs555404, rs558314, rs1799958) in the short chain acyl-CoA dehydrogenase gene (ACADS) were associated with neonatal C4 levels. Most significant was the G allele of rs2066938, which was associated with significantly higher levels of C4 (P=1.5×10−29). This SNP explains 25% of the variation in neonatal C4 levels, which is similar to the variation previously reported in adult C4 levels. There were also significant (P<1×10−4) associations between neonatal levels of C5-OH and SNPs in the solute carrier family 22 genes (SLC22A4 and SLC22A5) and the 3-methylcrotonyl-CoA carboxylase 1 gene (MCCC1). We have replicated, in newborns, SNP associations between metabolic traits and the ACADS and SLC22A4 genes observed in adults. This research has important implications not only for the identification of rare inborn errors of metabolism but also for personalized medicine and early detection of later life risks for chronic conditions. PMID:24850141

  10. Metabolic heritability at birth: implications for chronic disease research.

    PubMed

    Ryckman, Kelli K; Smith, Caitlin J; Jelliffe-Pawlowski, Laura L; Momany, Allison M; Berberich, Stanton L; Murray, Jeffrey C

    2014-08-01

    Recent genome-wide association studies of the adult human metabolome have identified genetic variants associated with relative levels of several acylcarnitines, which are important clinical correlates for chronic conditions such as type 2 diabetes and obesity. We have previously shown that these same metabolite levels are highly heritable at birth; however, no studies to our knowledge have examined genetic associations with these metabolites measured at birth. Here, we examine, in 743 newborns, 58 single nucleotide polymorphisms (SNPs) in 11 candidate genes previously associated with differing relative levels of short-chain acylcarnitines in adults. Six SNPs (rs2066938, rs3916, rs3794215, rs555404, rs558314, rs1799958) in the short-chain acyl-CoA dehydrogenase gene (ACADS) were associated with neonatal C4 levels. Most significant was the G allele of rs2066938, which was associated with significantly higher levels of C4 (P = 1.5 × 10(-29)). This SNP explains 25 % of the variation in neonatal C4 levels, which is similar to the variation previously reported in adult C4 levels. There were also significant (P < 1 × 10(-4)) associations between neonatal levels of C5-OH and SNPs in the solute carrier family 22 genes (SLC22A4 and SLC22A5) and the 3-methylcrotonyl-CoA carboxylase 1 gene (MCCC1). We have replicated, in newborns, SNP associations between metabolic traits and the ACADS and SLC22A4 genes observed in adults. This research has important implications not only for the identification of rare inborn errors of metabolism but also for personalized medicine and early detection of later life risks for chronic conditions.

  11. Pediatric Blood Pressure and Adult Preclinical Markers of Cardiovascular Disease

    PubMed Central

    Magnussen, Costan G.; Smith, Kylie J.

    2016-01-01

    A high blood pressure level in adults is considered the single most important modifiable risk factor for global disease burden, especially those of cardiovascular (CV) origin such as stroke and ischemic heart disease. Because blood pressure levels have been shown to persist from childhood to adulthood, elevations in pediatric levels have been hypothesized to lead to increased CV burden in adulthood and, as such, might provide a window in the life course where primordial and primary prevention could be focused. In the absence of substantive data directly linking childhood blood pressure levels to overt adult CV disease, this review outlines the available literature that examines the association between pediatric blood pressure and adult preclinical markers of CV disease. PMID:27168729

  12. METABOLIC SYNDROME AND NEUROMETABOLIC ASYMMETRY OF HIPPOCAMPUS IN ADULT BONNET MONKEYS

    PubMed Central

    Coplan, Jeremy D.; Abdallah, Chadi G.; Mathew, Sanjay J.; Shungu, Dikoma C.; Mao, Xiangling; Smith, Eric L.P.; Kaufman, Daniel; Gorman, Jack M.; Owens, Michael J.; Nemeroff, Charles B.; Banerji, Mary Ann; Rosenblum, Leonard A.; Kral, John G.

    2011-01-01

    Objective Obesity is associated with the insulin resistance metabolic syndrome, postulated to be mediated by stress-induced alterations within the hypothalamic-pituitary-adrenal (HPA) axis. In adult bonnet macaques we examined relationships between components of the metabolic syndrome, hippocampal neurometabolic asymmetry, an indicator of negative affect, and juvenile cerebrospinal fluid (csf) corticotropin-releasing factor (CRF) levels obtained after stress exposure associated with maternal food insecurity and in controls. Methods Eleven adult male monkeys (seven with early life stress) who had undergone csf-CRF analyses as juveniles had magnetic resonance spectroscopic imaging (MRSI) of bilateral hippocampus, morphometry (body mass index, BMI; sagittal abdominal diameter, SAD) and determination of fasting plasma glucose and insulin as adults. Neurometabolite ratios included N-acetyl-aspartate as numerator (NAA; a marker of neuronal integrity) and choline (Cho; cell turnover) and creatine (Cr; reference analyte) as denominators. Results Elevated juvenile csf-CRF levels positively predicted adult BMI and SAD and were associated with right > left shift of NAA ratio within the hippocampus. Adult visceral obesity and insulin level correlated with right > left shift in hippocampal NAA concentrations, controlling for age and denominator. Conclusion Juvenile csf-CRF levels, a neuropeptide associated with early life stress, predict adult visceral obesity and hippocampal asymmetry supporting the hypothesis that metabolic syndrome in adults may be related to early life stress. Furthermore, this study demonstrates asymmetrical hippocampal alterations related to obesity. PMID:21459102

  13. Epigenetic contributions to the developmental origins of adult lung disease.

    PubMed

    Joss-Moore, Lisa A; Lane, Robert H; Albertine, Kurt H

    2015-04-01

    Perinatal insults, including intrauterine growth restriction, preterm birth, maternal exposure to toxins, or dietary deficiencies produce deviations in the epigenome of lung cells. Occurrence of perinatal insults often coincides with the final stages of lung development. The result of epigenome disruptions in response to perinatal insults during lung development may be long-term structural and functional impairment of the lung and development of lung disease. Understanding the contribution of epigenetic mechanisms to life-long lung disease following perinatal insults is the focus of the developmental origins of adult lung disease field. DNA methylation, histone modifications, and microRNA changes are all observed in various forms of lung disease. However, the perinatal contribution to such epigenetic mechanisms is poorly understood. Here we discuss the developmental origins of adult lung disease, the interplay between perinatal events, lung development and disease, and the role that epigenetic mechanisms play in connecting these events.

  14. Is alexithymia associated with metabolic syndrome? A study in a healthy adult population.

    PubMed

    Karukivi, Max; Jula, Antti; Hutri-Kähönen, Nina; Juonala, Markus; Raitakari, Olli

    2016-02-28

    Metabolic syndrome (MetS) is a constellation of risk factors for, in particular, cardiovascular diseases and increased mortality, and it constitutes a major clinical challenge affecting millions of lives. Alexithymia is a condition that has been linked with several mental diseases and symptoms, as well as somatic illnesses, including essential hypertension and diabetes mellitus. However, there is limited research on the association of alexithymia and MetS. The aim of the present study was to comprehensively explore this association in a large (n=1648) non-clinical sample of adults. Logistic regression analyses were applied to the five separate MetS components as well as the MetS diagnosis, and the analyses included a number of sociodemographic variables and depressive symptoms as covariates. The results confirmed the previous finding of alexithymic features being independently and significantly associated with hypertension. As a new finding, this association appears to be related to two particular dimensions of alexithymia, namely difficulty describing feelings and externally oriented thinking. Interestingly, alexithymic features were also separately significantly associated with waist circumference and triglycerides as well as the MetS diagnosis. Depressive symptoms did not have any significant effect on the relations of alexithymia and MetS. PMID:26747214

  15. 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.

    PubMed

    Simopoulos, Artemis P

    2013-08-01

    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. PMID:23896654

  16. Magnesium Intake and Prevalence of Metabolic Syndrome in Older Adults

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Higher dietary intake of magnesium (Mg) may protect against development of type 2 diabetes. The aim of this study was to examine the association between dietary magnesium intake and metabolic syndrome risk factors in elderly men and women. We examined cross-sectional associations between magnesium i...

  17. A computer model simulating human glucose absorption and metabolism in health and metabolic disease states.

    PubMed

    Naftalin, Richard J

    2016-01-01

    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 implications on GLP

  18. A computer model simulating human glucose absorption and metabolism in health and metabolic disease states

    PubMed Central

    Naftalin, Richard J.

    2016-01-01

    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 implications on GLP

  19. Renal outcomes of bariatric surgery in obese adults with diabetic kidney disease.

    PubMed

    Rao, Bhavana B; Bhattacharya, Abhik; Agrawal, Varun

    2014-08-01

    Obesity is a pandemic with several significant adverse health outcomes. Chronic kidney disease has been an overlooked consequence of obesity. Among diabetics, obesity is known to amplify the risk for kidney disease. Although bariatric surgery promises significant and sustained weight reduction with favorable impact on metabolic parameters such as glycemic control, hypertension and dyslipidemia, its impact on the renal complications of diabetes is poorly understood. This paper aims to comprehensively evaluate the evidence in the published literature on the impact of bariatric surgery on renal outcomes in obese adults with diabetic kidney disease. While many observational studies have demonstrated significant reduction in proteinuria after bariatric surgery, there is paucity of data regarding changes in renal filtration function such as doubling of serum creatinine or progression to end stage kidney disease. No randomized controlled trials comparing medical vs. surgical therapy in obese adults with diabetic kidney disease exist, hence assessing the metabolic benefits vs. the surgical risks is important before recommending bariatric surgery to this growing patient population. Future studies require a collaborative effort between bariatric surgeons and nephrologists to measure long-term effects of bariatric surgery on renal outcomes incorporating evolving markers of kidney injury to advance this field.

  20. Adult-Onset Esophageal Crohn’s Disease

    PubMed Central

    Kasarala, George; Durrett, Sam

    2016-01-01

    Crohn’s disease (CD) is an idiopathic inflammatory bowel disease that can involve any part of the gastrointestinal tract. Esophageal involvement is rarely seen in adults, especially at the initial diagnosis of CD. Esophageal symptoms as primary manifestations of the disease are extremely rare. We report a case of a CD with esophageal involvement at the time of her initial diagnosis of CD. PMID:27761477

  1. The heart-liver metabolic axis: defective communication exacerbates disease.

    PubMed

    Baskin, Kedryn K; Bookout, Angie L; Olson, Eric N

    2014-04-01

    The heart has been recognized as an endocrine organ for over 30 years (de Bold, 2011); however, little is known about how the heart communicates with other organs in the body, and even less is known about this process in the diseased heart. In this issue of EMBO Molecular Medicine, Magida and Leinwand (2014) introduce the concept that a primary genetic defect in the heart results in aberrant hepatic lipid metabolism, which consequently exacerbates hypertrophic cardiomyopathy (HCM). This study provides evidence in support of the hypothesis that crosstalk occurs between the heart and liver, and that this becomes disrupted in the diseased state.

  2. Organelle pathology in metabolic neuromuscular disease: an overview.

    PubMed Central

    Becker, L E

    1990-01-01

    The spectrum of metabolic neuromuscular disorders is wide. Most inherited metabolic diseases are related to enzyme defects within lysosomes but recent advances emphasize abnormalities of mitochondria, peroxisomes and intermediate filaments. In this overview, organelle pathology is described in the context of both the clinical manifestations and the biochemical and/or molecular aspects of the disease. Among the many clinical presentations of mitochondrial disorders three emerge as distinctive entities: mitochondrial encephalopathy with lactic acidosis and stroke-like symptoms, mitochondrial encephalopathy with ragged-red fibers, and Kearns-Sayre syndrome. Peroxisomal disorders are associated with numerous biochemical defects, the most frequent of which are Zellweger's syndrome, neonatal adrenoleukodystrophy, and infantile Refsum's disease. Disorders of cytoskeletal proteins are associated with distinctive pathological accumulation of intermediate filaments but are without confirmed evidence of a biochemical defect. Understanding the role that organelle pathology plays in the pathogenesis of cellular disturbance or demise is essential to the elucidation of the pathogenesis of metabolic disorders. Images Fig. 1. Fig. 2. Fig. 3. Fig. 4. Fig. 5. Fig. 6. Fig. 7. Fig. 8. Fig. 9. Fig. 10. PMID:2407327

  3. Metabolic bone disease in home total parenteral nutrition.

    PubMed

    McCullough, M L; Hsu, N

    1987-07-01

    Home total parenteral nutrition (HTPN) is in its infancy but has proved to be lifesaving for patients unable to manage on enteral nutrition alone. However, this mode of nutrition therapy is not without problems. Aside from mechanical and other metabolic complications, a peculiar metabolic bone disease has been reported to occur in some HTPN recipients. The disease, characterized by abnormalities in calcium and phosphorus homeostasis, often results in osteomalacia, bone pain, and fractures. Reports of approximately 50 cases of metabolic bone disease have been published by centers in the United States and Canada. Factors that have been implicated as possible causes include infusion of excess vitamin D, aluminum, calcium, protein, or glucose; cyclic vs. continuous TPN administration; and the patient's previous nutritional state. Although removal of vitamin D or aluminum from the TPN solution and discontinuation of TPN altogether have been associated with improvement in symptoms, histology, and laboratory values, no single factor has been identified as the cause of this troubling phenomenon. PMID:3110249

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

    PubMed

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

    2016-08-01

    SEE HANSSON AND GOURAS DOI101093/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 < 0.001) were maintained both in Pittsburgh compound B-negative cognitively normal older subjects (T = 6.66, P < 0.001) and Pittsburgh compound B-positive cognitively normal older subjects (T

  5. Linking Early Environmental Exposures to Adult Diseases

    MedlinePlus

    ... David Barker, for example, put forward the “fetal programming or developmental basis of health and disease” hypothesis, ... mechanisms by which fetal insults lead to altered programming and to disease later in life. RESEARCH FINDINGS ...

  6. Integrative neurobiology of metabolic diseases, neuroinflammation, and neurodegeneration

    PubMed Central

    van Dijk, Gertjan; van Heijningen, Steffen; Reijne, Aaffien C.; Nyakas, Csaba; van der Zee, Eddy A.; Eisel, Ulrich L. M.

    2015-01-01

    Alzheimer's disease (AD) is a complex, multifactorial disease with a number of leading mechanisms, including neuroinflammation, processing of amyloid precursor protein (APP) to amyloid β peptide, tau protein hyperphosphorylation, relocalization, and deposition. These mechanisms are propagated by obesity, the metabolic syndrome and type-2 diabetes mellitus. Stress, sedentariness, dietary overconsumption of saturated fat and refined sugars, and circadian derangements/disturbed sleep contribute to obesity and related metabolic diseases, but also accelerate age-related damage and senescence that all feed the risk of developing AD too. The complex and interacting mechanisms are not yet completely understood and will require further analysis. Instead of investigating AD as a mono- or oligocausal disease we should address the disease by understanding the multiple underlying mechanisms and how these interact. Future research therefore might concentrate on integrating these by “systems biology” approaches, but also to regard them from an evolutionary medicine point of view. The current review addresses several of these interacting mechanisms in animal models and compares them with clinical data giving an overview about our current knowledge and puts them into an integrated framework. PMID:26041981

  7. Common links between metabolic syndrome and inflammatory bowel disease: Current overview and future perspectives.

    PubMed

    Michalak, Arkadiusz; Mosińska, Paula; Fichna, Jakub

    2016-08-01

    Metabolic syndrome (MS) features a constellation of central obesity, dyslipidemia, impaired glucose metabolism and often hypertension joined by insulin resistance and chronic inflammation. All these elements greatly raise patient's risk of cardiovascular disease and type 2 diabetes, resulting in an increased mortality. Metabolic syndrome affects approximately 20-25% of the world's adult population and thus it is essential to study its pathophysiology and seek new pharmacological targets. There is a thoroughly studied link between MS and inflammatory diseases of the gastrointestinal (GI) system, i.e. steatohepatitis. However, recent findings also indicate similarities in pathophysiological features between MS and inflammatory bowel disease (IBD), including adipose tissue dysregulation, inadequate immune response, and inflammation. In this review we aim to outline the pathophysiology of MS and emphasize the aspects revealed recently, such as mineralocorticoid activity, involvement of sex hormones and an accompanying increase in prolactin secretion. More importantly, we focus on the common links between MS and IBD. Finally, we describe new strategies and drug targets that may be utilized in MS therapy, namely adiponectin mimetics, GLP-1-based multi agonists, ABCA1 agonists and possible role of miRNA. We also discuss the possible utility of selected agents as adjuvants in IBD therapy.

  8. Adult neurogenesis in the olfactory system and neurodegenerative disease.

    PubMed

    Gallarda, B W; Lledo, P-M

    2012-12-01

    The olfactory system is unique in many respects-two of which include the process of adult neurogenesis which continually supplies it with newborn neurons, and the fact that neurodegenerative diseases are often accompanied by a loss of smell. A link between these two phenomena has been hypothesized, but recent evidence for the lack of robust adult neurogenesis in the human olfactory system calls into question this hypothesis. Nevertheless, model organisms continue to play a critical role in the exploration of neurodegenerative disease. In part one of this review we discuss the most promising recent technological advancements for studying adult neurogenesis in the murine olfactory system. Part two continues by looking at emerging evidence related to adult neurogenesis in neurodegenerative disease studied in model organisms and the differences between animal and human olfactory system adult neurogenesis. Hopefully, the careful application of advanced research methods to the study of neurodegenerative disease in model organisms, while taking into account the recently reported differences between the human and model organism olfactory system, will lead to a better understanding of the reasons for the susceptibility of olfaction to disease.

  9. Coats’ disease of adult-onset in 48 eyes

    PubMed Central

    Rishi, Ekta; Rishi, Pukhraj; Appukuttan, Bindu; Uparkar, Mahesh; Sharma, Tarun; Gopal, Lingam

    2016-01-01

    Background: Coats’ disease diagnosed in adulthood is an idiopathic, retinal exudative vascular disease without an inciting factor and has retinal features different from the childhood disease. Aim: To describe clinical features, treatment, and outcomes of eyes with Coats’ disease first diagnosed in patients 35 years or older. Materials and Methods: Retrospective chart review of patients first diagnosed with Coats’ disease at the age of 35 years or more at a tertiary eye care center between January 1995 and 2012. Eyes with retinal exudation or Coats’-like response from secondary causes were excluded. Results: Forty-five of 646 patients (7%) diagnosed with Coats’ disease had adult-onset disease. Mean age at presentation was 47 years. Systemic hypertension was the most common (22%) systemic association and decreased vision the predominant presenting feature (83%). Localized (<6 clock h) presentation (74%) was unique to adults as against diffuse involvement (69%) in children (P < 0.001). Eyes were treated with laser photocoagulation 29 (60%), cryotherapy (4%), or both (2%) with surgical intervention in three (6%) eyes. Following treatment eight (35%) eyes improved, 11 (48%) eyes were stable while four (12%) eyes worsened due to complications. Conclusion: Adult-onset Coats’ disease has less extensive involvement, more benign natural course, and a more favorable treatment outcome as against the childhood-onset disease. The bilateral presentation emphasizes the need for regular follow-up to detect possible future involvement of the fellow eye. PMID:27609165

  10. Metabolic Signatures of Adiposity in Young Adults: Mendelian Randomization Analysis and Effects of Weight Change

    PubMed Central

    Würtz, Peter; Wang, Qin; Kangas, Antti J.; Richmond, Rebecca C.; Skarp, Joni; Tiainen, Mika; Tynkkynen, Tuulia; Soininen, Pasi; Havulinna, Aki S.; Kaakinen, Marika; Viikari, Jorma S.; Savolainen, Markku J.; Kähönen, Mika; Lehtimäki, Terho; Männistö, Satu; Blankenberg, Stefan; Zeller, Tanja; Laitinen, Jaana; Pouta, Anneli; Mäntyselkä, Pekka; Vanhala, Mauno; Elliott, Paul; Pietiläinen, Kirsi H.; Ripatti, Samuli; Salomaa, Veikko; Raitakari, Olli T.; Järvelin, Marjo-Riitta; Smith, George Davey; Ala-Korpela, Mika

    2014-01-01

    Background Increased adiposity is linked with higher risk for cardiometabolic diseases. We aimed to determine to what extent elevated body mass index (BMI) within the normal weight range has causal effects on the detailed systemic metabolite profile in early adulthood. Methods and Findings We used Mendelian randomization to estimate causal effects of BMI on 82 metabolic measures in 12,664 adolescents and young adults from four population-based cohorts in Finland (mean age 26 y, range 16–39 y; 51% women; mean ± standard deviation BMI 24±4 kg/m2). Circulating metabolites were quantified by high-throughput nuclear magnetic resonance metabolomics and biochemical assays. In cross-sectional analyses, elevated BMI was adversely associated with cardiometabolic risk markers throughout the systemic metabolite profile, including lipoprotein subclasses, fatty acid composition, amino acids, inflammatory markers, and various hormones (p<0.0005 for 68 measures). Metabolite associations with BMI were generally stronger for men than for women (median 136%, interquartile range 125%–183%). A gene score for predisposition to elevated BMI, composed of 32 established genetic correlates, was used as the instrument to assess causality. Causal effects of elevated BMI closely matched observational estimates (correspondence 87%±3%; R2 = 0.89), suggesting causative influences of adiposity on the levels of numerous metabolites (p<0.0005 for 24 measures), including lipoprotein lipid subclasses and particle size, branched-chain and aromatic amino acids, and inflammation-related glycoprotein acetyls. Causal analyses of certain metabolites and potential sex differences warrant stronger statistical power. Metabolite changes associated with change in BMI during 6 y of follow-up were examined for 1,488 individuals. Change in BMI was accompanied by widespread metabolite changes, which had an association pattern similar to that of the cross-sectional observations, yet with greater metabolic

  11. Insulin-like growth factor-II: its role in metabolic and endocrine disease.

    PubMed

    Livingstone, Callum; Borai, Anwar

    2014-06-01

    Insulin-like growth factor-II (IGF-II) is a widely expressed 7·5 kDa mitogenic peptide hormone. Although it is abundant in serum, understanding of its physiological role is limited compared with that of IGF-I. IGF-II regulates foetal development and differentiation, but its role in adults is less well understood. Evidence suggests roles in a number of tissues including skeletal muscle, adipose tissue, bone and ovary. Altered IGF-II expression has been observed in metabolic conditions, notably obesity, diabetes and the polycystic ovary syndrome. This article summarizes what is known about the actions of IGF-II and its dysregulation in metabolic and endocrine diseases. The possible causes and consequences of dysregulation are discussed along with the implications for diagnostic tests and future research.

  12. Long-Term Exposure to Ambient Air Pollution and Metabolic Syndrome in Adults

    PubMed Central

    Eze, Ikenna C.; Schaffner, Emmanuel; Foraster, Maria; Imboden, Medea; von Eckardstein, Arnold; Gerbase, Margaret W.; Rothe, Thomas; Rochat, Thierry; Künzli, Nino; Schindler, Christian; Probst-Hensch, Nicole

    2015-01-01

    Air pollutants (AP) play a role in subclinical inflammation, and are associated with cardiovascular morbidity and mortality. Metabolic syndrome (MetS) is inflammatory and precedes cardiovascular morbidity and type 2 diabetes. Thus, a positive association between AP and MetS may be hypothesized. We explored this association, (taking into account, pathway-specific MetS definitions), and its potential modifiers in Swiss adults. We studied 3769 participants of the Swiss Cohort Study on Air Pollution and Lung and Heart Diseases in Adults, reporting at least four-hour fasting time before venepuncture. AP exposures were 10-year mean residential PM10 (particulate matter <10μm in diameter) and NO2 (nitrogen dioxide). Outcomes included MetS defined by World Health Organization (MetS-W), International Diabetes Federation (MetS-I) and Adult Treatment Panel-III (MetS-A) using four- and eight-hour fasting time limits. We also explored associations with individual components of MetS. We applied mixed logistic regression models to explore these associations. The prevalence of MetS-W, MetS-I and MetS-A were 10%, 22% and 18% respectively. Odds of MetS-W, MetS-I and MetS-A increased by 72% (51-102%), 31% (11-54%) and 18% (4-34%) per 10μg/m3 increase in 10-year mean PM10. We observed weaker associations with NO2. Associations were stronger among physically-active, ever-smokers and non-diabetic participants especially with PM10 (p<0.05). Associations remained robust across various sensitivity analyses including ten imputations of missing observations and exclusion of diabetes cases. The observed associations between AP exposure and MetS were sensitive to MetS definitions. Regarding the MetS components, we observed strongest associations with impaired fasting glycemia, and positive but weaker associations with hypertension and waist-circumference-based obesity. Cardio-metabolic effects of AP may be majorly driven by impairment of glucose homeostasis, and to a less-strong extent

  13. Long-Term Exposure to Ambient Air Pollution and Metabolic Syndrome in Adults.

    PubMed

    Eze, Ikenna C; Schaffner, Emmanuel; Foraster, Maria; Imboden, Medea; von Eckardstein, Arnold; Gerbase, Margaret W; Rothe, Thomas; Rochat, Thierry; Künzli, Nino; Schindler, Christian; Probst-Hensch, Nicole

    2015-01-01

    Air pollutants (AP) play a role in subclinical inflammation, and are associated with cardiovascular morbidity and mortality. Metabolic syndrome (MetS) is inflammatory and precedes cardiovascular morbidity and type 2 diabetes. Thus, a positive association between AP and MetS may be hypothesized. We explored this association, (taking into account, pathway-specific MetS definitions), and its potential modifiers in Swiss adults. We studied 3769 participants of the Swiss Cohort Study on Air Pollution and Lung and Heart Diseases in Adults, reporting at least four-hour fasting time before venepuncture. AP exposures were 10-year mean residential PM10 (particulate matter <10μm in diameter) and NO2 (nitrogen dioxide). Outcomes included MetS defined by World Health Organization (MetS-W), International Diabetes Federation (MetS-I) and Adult Treatment Panel-III (MetS-A) using four- and eight-hour fasting time limits. We also explored associations with individual components of MetS. We applied mixed logistic regression models to explore these associations. The prevalence of MetS-W, MetS-I and MetS-A were 10%, 22% and 18% respectively. Odds of MetS-W, MetS-I and MetS-A increased by 72% (51-102%), 31% (11-54%) and 18% (4-34%) per 10μg/m3 increase in 10-year mean PM10. We observed weaker associations with NO2. Associations were stronger among physically-active, ever-smokers and non-diabetic participants especially with PM10 (p<0.05). Associations remained robust across various sensitivity analyses including ten imputations of missing observations and exclusion of diabetes cases. The observed associations between AP exposure and MetS were sensitive to MetS definitions. Regarding the MetS components, we observed strongest associations with impaired fasting glycemia, and positive but weaker associations with hypertension and waist-circumference-based obesity. Cardio-metabolic effects of AP may be majorly driven by impairment of glucose homeostasis, and to a less-strong extent

  14. Proximal correlates of metabolic phenotypes during ‘at-risk' and ‘case' stages of the metabolic disease continuum

    PubMed Central

    Haren, M T; Misan, G; Grant, J F; Buckley, J D; Howe, P R C; Taylor, A W; Newbury, J; McDermott, R A

    2012-01-01

    Objective: To examine the social and behavioural correlates of metabolic phenotypes during ‘at-risk' and ‘case' stages of the metabolic disease continuum. Design: Cross-sectional study of a random population sample. Participants: A total of 718 community-dwelling adults (57% female), aged 18–92 years from a regional South Australian city. Measurements: Total body fat and lean mass and abdominal fat mass were assessed by dual energy x-ray absorptiometry. Fasting venous blood was collected in the morning for assessment of glycated haemoglobin, plasma glucose, serum triglycerides, cholesterol lipoproteins and insulin. Seated blood pressure (BP) was measured. Physical activity and smoking, alcohol and diet (96-item food frequency), sleep duration and frequency of sleep disordered breathing (SDB) symptoms, and family history of cardiometabolic disease, education, lifetime occupation and household income were assessed by questionnaire. Current medications were determined by clinical inventory. Results: 36.5% were pharmacologically managed for a metabolic risk factor or had known diabetes (‘cases'), otherwise were classified as the ‘at-risk' population. In both ‘at-risk' and ‘cases', four major metabolic phenotypes were identified using principal components analysis that explained over 77% of the metabolic variance between people: fat mass/insulinemia (FMI); BP; lipidaemia/lean mass (LLM) and glycaemia (GLY). The BP phenotype was uncorrelated with other phenotypes in ‘cases', whereas all phenotypes were inter-correlated in the ‘at-risk'. Over and above other socioeconomic and behavioural factors, medications were the dominant correlates of all phenotypes in ‘cases' and SDB symptom frequency was most strongly associated with FMI, LLM and GLY phenotypes in the ‘at-risk'. Conclusion: Previous research has shown FMI, LLM and GLY phenotypes to be most strongly predictive of diabetes development. Reducing SDB symptom frequency and optimising the duration

  15. Metabolic bone disease in children : etiology and treatment options.

    PubMed

    Skowrońska-Jóźwiak, Elzbieta; Lorenc, Roman S

    2006-01-01

    Metabolic bone disease in children includes many hereditary and acquired conditions of diverse etiology that lead to disturbed metabolism of the bone tissue. Some of these processes primarily affect bone; others are secondary to nutritional deficiencies, a variety of chronic disorders, and/or treatment with some drugs. Some of these disorders are rare, but some present public health concerns (for instance, rickets) that have been well known for many years but still persist. The most important clinical consequences of bone metabolic diseases in the pediatric population include reduced linear growth, bone deformations, and non-traumatic fractures leading to bone pain, deterioration of motor development and disability. In this article, we analyze primary and secondary osteoporosis, rickets, osteomalacia (nutritional and hereditary vitamin D-dependent, hypophosphatemic and that due to renal tubular abnormalities), renal osteodystrophy, sclerosing bony disorders, and some genetic bone diseases (hypophosphatasia, fibrous dysplasia, skeletal dysplasia, juvenile Paget disease, familial expansile osteolysis, and osteoporosis pseudoglioma syndrome). Early identification and treatment of potential risk factors is essential for skeletal health in adulthood. In most conditions it is necessary to ensure an appropriate diet, with calcium and vitamin D, and an adequate amount of physical activity as a means of prevention. In secondary bone diseases, treatment of the primary disorder is crucial. Most genetic disorders await prospective gene therapies, while bone marrow transplantation has been attempted in other disorders. At present, affected patients are treated symptomatically, frequently by interdisciplinary teams. The role of exercise and pharmacologic therapy with calcium, vitamin D, phosphate, bisphosphonates, calcitonin, sex hormones, growth hormone, and thiazides is discussed. The perspectives on future therapy with insulin-like growth factor-1, new analogs of vitamin D

  16. Dietary Patterns of Korean Adults and the Prevalence of Metabolic Syndrome: A Cross-Sectional Study

    PubMed Central

    Woo, Hae Dong; Shin, Aesun; Kim, Jeongseon

    2014-01-01

    The prevalence of metabolic syndrome has been increasing in Korea and has been associated with dietary habits. The aim of our study was to identify the relationship between dietary patterns and the prevalence of metabolic syndrome. Using a validated food frequency questionnaire, we employed a cross-sectional design to assess the dietary intake of 1257 Korean adults aged 31 to 70 years. To determine the participants’ dietary patterns, we considered 37 predefined food groups in principal components analysis. Metabolic syndrome was defined according to the National Cholesterol Education Program Adult Treatment Panel III. The abdominal obesity criterion was modified using Asian guidelines. Prevalence ratios and 95% confidence intervals for the metabolic syndrome were calculated across the quartiles of dietary pattern scores using log binomial regression models. The covariates used in the model were age, sex, total energy intake, tobacco intake, alcohol consumption, and physical activity. The prevalence of metabolic syndrome was 19.8% in men and 14.1% in women. The PCA identified three distinct dietary patterns: the ‘traditional’ pattern, the ‘meat’ pattern, and the ‘snack’ pattern. There was an association of increasing waist circumference and body mass index with increasing score in the meat dietary pattern. The multivariate-adjusted prevalence ratio of metabolic syndrome for the highest quartile of the meat pattern in comparison with the lowest quartile was 1.47 (95% CI: 1.00–2.15, p for trend = 0.016). A positive association between the prevalence of metabolic syndrome and the dietary pattern score was found only for men with the meat dietary pattern (2.15, 95% CI: 1.10–4.21, p for trend = 0.005). The traditional pattern and the snack pattern were not associated with an increased prevalence of metabolic syndrome. The meat dietary pattern was associated with a higher prevalence of metabolic syndrome in Korean male adults. PMID:25365577

  17. Severe metabolic acidosis in adult patients with Duchenne muscular dystrophy.

    PubMed

    Lo Cascio, Christian M; Latshang, Tsogyal D; Kohler, Malcolm; Fehr, Thomas; Bloch, Konrad E

    2014-01-01

    Duchenne muscular dystrophy (DMD) leads to progressive paresis, respiratory failure and premature death. Long-term positive pressure ventilation can improve quality of life and survival, but previously unrecognized complications may arise. We analyzed the characteristics of severe metabolic acidosis occurring in 8 of 55 DMD patients, of 20-36 years of age, observed over a 5-year period. All patients were on positive pressure ventilation and were being treated for chronic constipation. Before admission, they had had a reduced intake of fluids and food. Upon examination, they were severely ill, dyspneic and suffering from abdominal discomfort. Metabolic acidosis with a high anion gap was noted in 5 of the 8 patients and with a normal anion gap in the other 3. They all recovered after the administration of fluids and nutrition, the regulation of bowel movements and treatment with antibiotics, as appropriate. Metabolic acidosis is a life-threatening, potentially preventable complication in older DMD patients. Early recognition, subsequent administration of fluids, nutrition and antibiotics and regulation of bowel movements seem to be essential.

  18. The Emerging Adult with Inflammatory Bowel Disease: Challenges and Recommendations for the Adult Gastroenterologist

    PubMed Central

    Keefer, Laurie

    2015-01-01

    Incidence of pediatric inflammatory bowel disease (IBD) is rising. Adult gastroenterologists are seeing increasing numbers of young adults with IBD, a subpopulation with unique needs and challenges that can impair their readiness to thrive in an adult healthcare system. Most adult gastroenterologists might not have the training or resources to address these needs. “Emerging adulthood” is a useful developmental lens through which this group can be studied. With complex disease phenotype and specific concerns of medication side effects and reproductive health, compounded by challenges of geographical and social flux and lack of adequate health insurance, emerging adults with IBD (EAI) are at risk of disrupted care with lack of continuity. Lessons learned from structured healthcare transition process from pediatric to adult services can be applied towards challenges in ongoing care of this population in the adult healthcare system. This paper provides an overview of the challenges in caring for the post transition EAI from the perspective of adult gastroenterologists and offers a checklist of provider and patient skills that enable effective care. This paper discusses the system-based challenges in care provision and search for meaningful patient-oriented outcomes and presents a conceptual model of determinants of continuity of care in this unique population. PMID:26064089

  19. The emerging use of zebrafish to model metabolic disease

    PubMed Central

    Seth, Asha; Stemple, Derek L.; Barroso, Inês

    2013-01-01

    The zebrafish research community is celebrating! The zebrafish genome has recently been sequenced, the Zebrafish Mutation Project (launched by the Wellcome Trust Sanger Institute) has published the results of its first large-scale ethylnitrosourea (ENU) mutagenesis screen, and a host of new techniques, such as the genome editing technologies TALEN and CRISPR-Cas, are enabling specific mutations to be created in model organisms and investigated in vivo. The zebrafish truly seems to be coming of age. These powerful resources invoke the question of whether zebrafish can be increasingly used to model human disease, particularly common, chronic diseases of metabolism such as obesity and type 2 diabetes. In recent years, there has been considerable success, mainly from genomic approaches, in identifying genetic variants that are associated with these conditions in humans; however, mechanistic insights into the role of implicated disease loci are lacking. In this Review, we highlight some of the advantages and disadvantages of zebrafish to address the organism’s utility as a model system for human metabolic diseases. PMID:24046387

  20. Black leaf streak disease affects starch metabolism in banana fruit.

    PubMed

    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. PMID:23692371

  1. Impact of DHA on Metabolic Diseases from Womb to Tomb

    PubMed Central

    Arnoldussen, Ilse A. C.; Kiliaan, Amanda J.

    2014-01-01

    Long chain polyunsaturated fatty acids (LC-PUFAs) are important mediators in improving and maintaining human health over the total lifespan. One topic we especially focus on in this review is omega-3 LC-PUFA docosahexaenoic acid (DHA). Adequate DHA levels are essential during neurodevelopment and, in addition, beneficial in cognitive processes throughout life. We review the impact of DHA on societal relevant metabolic diseases such as cardiovascular diseases, obesity, and diabetes mellitus type 2 (T2DM). All of these are risk factors for cognitive decline and dementia in later life. DHA supplementation is associated with a reduced incidence of both stroke and atherosclerosis, lower bodyweight and decreased T2DM prevalence. These findings are discussed in the light of different stages in the human life cycle: childhood, adolescence, adulthood and in later life. From this review, it can be concluded that DHA supplementation is able to inhibit pathologies like obesity and cardiovascular disease. DHA could be a dietary protector against these metabolic diseases during a person’s entire lifespan. However, supplementation of DHA in combination with other dietary factors is also effective. The efficacy of DHA depends on its dose as well as on the duration of supplementation, sex, and age. PMID:25528960

  2. Mitochondrial disease in adults: what's old and what's new?

    PubMed

    Chinnery, Patrick F

    2015-11-26

    Ten years ago, there was an emerging view that the molecular basis for adult mitochondrial disorders was largely known and that the clinical phenotypes had been well described. Nothing could have been further from the truth. The establishment of large cohorts of patients has revealed new aspects of the clinical presentation that were not previously appreciated. Over time, this approach is starting to provide an accurate understanding of the natural history of mitochondrial disease in adults. Advances in molecular diagnostics, underpinned by next generation sequencing technology, have identified novel molecular mechanisms. Recently described mitochondrial disease phenotypes have disparate causes, and yet share common mechanistic themes. In particular, disorders of mtDNA maintenance have emerged as a major cause of mitochondrial disease in adults. Progressive mtDNA depletion and the accumulation of mtDNA mutations explain some of the clinical features, but the genetic and cellular processes responsible for the mtDNA abnormalities are not entirely clear in each instance. Unfortunately, apart from a few specific examples, treatments for adult mitochondrial disease have not been forthcoming. However, the establishment of international consortia, and the first multinational randomised controlled trial, have paved the way for major progress in the near future, underpinned by growing interest from the pharmaceutical industry. Adult mitochondrial medicine is, therefore, in its infancy, and the challenge is to harness the new understanding of its molecular and cellular basis to develop treatments of real benefit to patients.

  3. Disorders of Iron Metabolism and Anemia in Chronic Kidney Disease.

    PubMed

    Panwar, Bhupesh; Gutiérrez, Orlando M

    2016-07-01

    Dysregulated iron homeostasis plays a central role in the development of anemia of chronic kidney disease (CKD) and is a major contributor toward resistance to treatment with erythropoiesis-stimulating agents. Understanding the underlying pathophysiology requires an in-depth understanding of normal iron physiology and regulation. Recent discoveries in the field of iron biology have greatly improved our understanding of the hormonal regulation of iron trafficking in human beings and how its alterations lead to the development of anemia of CKD. In addition, emerging evidence has suggested that iron homeostasis interacts with bone and mineral metabolism on multiple levels, opening up new avenues of investigation into the genesis of disordered iron metabolism in CKD. Building on recent advances in our understanding of normal iron physiology and abnormalities in iron homeostasis in CKD, this review characterizes how anemia related to disordered iron metabolism develops in the setting of CKD. In addition, this review explores our emerging recognition of the connections between iron homeostasis and mineral metabolism and their implications for the management of altered iron status and anemia of CKD.

  4. [Alteration of biological rhythms causes metabolic diseases and obesity].

    PubMed

    Saderi, Nadia; Escobar, Carolina; Salgado-Delgado, Roberto

    2013-07-16

    The incidence of obesity worldwide has become a serious, constantly growing public health issue that reaches alarming proportions in some countries. To date none of the strategies developed to combat obesity have proved to be decisive, and hence there is an urgent need to address the problem with new approaches. Today, studies in the field of chronobiology have shown that our physiology continually adapts itself to the cyclical changes in the environment, regard-less of whether they are daily or seasonal. This is possible thanks to the existence of a biological clock in our hypothalamus which regulates the expression and/or activity of enzymes and hormones involved in regulating our metabolism, as well as all the homeostatic functions. It has been observed that this clock can be upset as a result of today's modern lifestyle, which involves a drop in physical activity during the day and the abundant ingestion of food during the night, among other factors, which together promote metabolic syndrome and obesity. Hence, the aim of this review is to summarise the recent findings that show the effect that altering the circadian rhythms has on the metabolism and how this can play a part in the development of metabolic diseases.

  5. Disorders of Iron Metabolism and Anemia in Chronic Kidney Disease.

    PubMed

    Panwar, Bhupesh; Gutiérrez, Orlando M

    2016-07-01

    Dysregulated iron homeostasis plays a central role in the development of anemia of chronic kidney disease (CKD) and is a major contributor toward resistance to treatment with erythropoiesis-stimulating agents. Understanding the underlying pathophysiology requires an in-depth understanding of normal iron physiology and regulation. Recent discoveries in the field of iron biology have greatly improved our understanding of the hormonal regulation of iron trafficking in human beings and how its alterations lead to the development of anemia of CKD. In addition, emerging evidence has suggested that iron homeostasis interacts with bone and mineral metabolism on multiple levels, opening up new avenues of investigation into the genesis of disordered iron metabolism in CKD. Building on recent advances in our understanding of normal iron physiology and abnormalities in iron homeostasis in CKD, this review characterizes how anemia related to disordered iron metabolism develops in the setting of CKD. In addition, this review explores our emerging recognition of the connections between iron homeostasis and mineral metabolism and their implications for the management of altered iron status and anemia of CKD. PMID:27475656

  6. Metabolism and cold tolerance of overwintering adult mountain pine beetles (Dendroctonus ponderosae): evidence of facultative diapause?

    PubMed

    Lester, Jack D; Irwin, Jason T

    2012-06-01

    We sought evidence for a distinct diapause in adult overwintering mountain pine beetles (Dendroctonus ponderosae Hopkins) by measuring metabolic rate and supercooling ability of field collected beetles throughout the year. Metabolic rates measured at 0, 5, and 10°C declined significantly from October through November, then rose slowly, reaching levels as high as those recorded in October by late May. From December to February metabolic rates were not correlated with minimum weekly phloem temperatures (R(2)=0.0%, P=0.592), but were correlated with phloem temperatures as winter advanced to spring (R(2)=44.8%, P=0.010), a pattern consistent with progression through the maintenance and termination phases of diapause. Supercooling points were also significantly lower in winter compared to fall and spring (F((8,143))=32.6, P<0.001) and were closely correlated with metabolic rates (R(2)>79% for all three temperatures). Dry mass declined linearly with winter progression (F((8,150))=8.34, P<0.001), explained by catabolism of metabolic reserves, with a concomitant accumulation of metabolic water (F((8,147))=35.24, P<0.001). The strong mid-winter metabolic suppression correlated with improved supercooling ability, coupled with their lack of response to variation in environmental temperature, are evidence of possible diapause in adult overwintering mountain pine beetles.

  7. Nutrition in adult patients with inflammatory bowel disease.

    PubMed

    Hebuterne, Xavier; Filippi, Jerome; Schneider, Stephane M

    2014-01-01

    Seventy five percent of hospitalized patients with Crohn's disease suffer from malnutrition. One third of Crohn's disease patients have a body mass index below 20. Sixty percent of Crohn's disease patients have sarcopenia. However some inflammatory bowel disease (IBD) patients are obese or suffer from sarcopenic-obesity. IBD patients have many vitamin and nutrient deficiencies, which can lead to important consequences such as hyperhomocysteinemia, which is associated with a higher risk of thromboembolic disease. Nutritional deficiencies in IBD patients are the result of insufficient intake, malabsorption and protein-losing enteropathy as well as metabolic disturbances directly induced by the chronic disease and its treatments, in particular corticosteroids. Screening for nutritional deficiencies in chronic disease patients is warranted. Managing the deficiencies involves simple nutritional guidelines, vitamin supplements, and nutritional support in the worst cases. PMID:25266810

  8. Molecular links between early energy metabolism alterations and Alzheimer's disease.

    PubMed

    Pedros, Ignacio; Patraca, Ivan; Martinez, Nohora; Petrov, Dmitry; Sureda, Francesc X; Auladell, Carme; Beas-Zarate, Carlos; Folch, Jaume

    2016-01-01

    Recent studies suggest that the neurobiology of Alzheimer's disease (AD) pathology could not be explained solely by an increase in beta-amyloid levels. In fact, success with potential therapeutic drugs that inhibit the generation of beta amyloid has been low. Therefore, due to therapeutic failure in recent years, the scientists are looking for alternative hypotheses to explain the causes of the disease and the cognitive loss. Accordingly, alternative hypothesis propose a link between AD and peripheral metabolic alteration. Then, we review in depth changes related to insulin signalling and energy metabolism in the context of the APPSwe/PS1dE9 (APP/PS1) mice model of AD. We show an integrated view of the changes that occur in the early stages of the amyloidogenic process in the APP/PS1 double transgenic mice model. These early changes affect several key metabolic processes related to glucose uptake and insulin signalling, cellular energy homeostasis, mitochondrial biogenesis and increased Tau phosphorylation by kinase molecules like mTOR and Cdk5.

  9. Pregnancy and Adult Congenital Heart Disease.

    PubMed

    Bhatt, Ami B; DeFaria Yeh, Doreen

    2015-11-01

    Most women with known congenital heart disease can have successful pregnancy, labor, and delivery. Preconception assessment is essential in understanding anatomy, repairs, and current physiology, all of which can influence risk in pregnancy. With that foundation, a multidisciplinary cardio-obstetric team can predict and prepare for complications that may occur with superimposed hemodynamic changes of pregnancy. Individuals with Eisenmenger syndrome, pulmonary hypertension, cyanosis, significant left heart obstruction, ventricular dysfunction, or prior major cardiac event are among the highest risk for complications.

  10. [Developmental programming of metabolic diseases--a review of studies on experimental animal models].

    PubMed

    Piotrowska, Iwona; Zgódka, Paulina; Milewska, Marta; Błaszczyk, Maciej; Grzelkowska-Kowalczyk, Katarzyna

    2014-01-01

    Growth and development in utero is a complex and dynamic process that requires interaction between the mother organism and the fetus. The delivery of macro--and micronutrients, oxygen and endocrine signals has crucial importance for providing a high level of proliferation, growth and differentiation of cells, and a disruption in food intake not only has an influence on the growth of the fetus, but also has negative consequences for the offspring’s health in the future. Diseases that traditionally are linked to inappropriate life style of adults, such as type 2 diabetes, obesity, and arterial hypertension, can be "programmed" in the early stage of life and the disturbed growth of the fetus leads to the symptoms of the metabolic syndrome. The structural changes of some organs, such as the brain, pancreas and kidney, modifications of the signaling and metabolic pathways in skeletal muscles and in fatty tissue, epigenetic mechanisms and mitochondrial dysfunction are the basis of the metabolic disruptions. The programming of the metabolic disturbances is connected with the disruption in the intrauterine environment experienced in the early and late gestation period. It causes the changes in deposition of triglycerides, activation of the hormonal "stress axis" and disturbances in the offspring’s glucose tolerance. The present review summarizes experimental results that led to the identification of the above-mentioned links and it underlines the role of animal models in the studies of this important concept.

  11. Metabolic Syndrome and Short-Term Heart Rate Variability in Adults with Intellectual Disabilities

    ERIC Educational Resources Information Center

    Chang, Yaw-Wen; Lin, Jin-Ding; Chen, Wei-Liang; Yen, Chia-Feng; Loh, Ching-Hui; Fang, Wen-Hui; Wu, Li-Wei

    2012-01-01

    Metabolic syndrome (MetS) increases the risk of cardiovascular events. Heart rate variability (HRV) represents autonomic functioning, and reduced HRV significantly increases cardiovascular mortality. The aims of the present paper are to assess the prevalence of MetS in adults with intellectual disabilities (ID), the difference in short-term HRV…

  12. Carotid body, insulin, and metabolic diseases: unraveling the links

    PubMed Central

    Conde, Sílvia V.; Sacramento, Joana F.; Guarino, Maria P.; Gonzalez, Constancio; Obeso, Ana; Diogo, Lucilia N.; Monteiro, Emilia C.; Ribeiro, Maria J.

    2014-01-01

    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 apnea (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. PMID:25400585

  13. Maternal perinatal undernutrition modifies lactose and serotranferrin in milk: relevance to the programming of metabolic diseases?

    PubMed

    Wattez, J S; Delmont, A; Bouvet, M; Beseme, O; Goers, S; Delahaye, F; Laborie, C; Lesage, J; Foligné, B; Breton, C; Metges, C C; Vieau, D; Pinet, F

    2015-03-01

    A close link between intrauterine growth restriction and development of chronic adult diseases such as obesity, diabetes, and hypertension has been established both in humans and animals. Modification of growth velocity during the early postnatal period (i.e., lactation) may also sensitize to the development of metabolic syndrome in adulthood. This suggests that milk composition may have long-lasting programming/deprogramming metabolic effects in the offspring. We therefore assess the effects of maternal perinatal denutrition on breast milk composition in a food-restricted 50% (FR50) rat model. Monosaccharides and fatty acids were characterized by gas chromatography, and proteins were profiled by surface-enhanced laser desorption/ionization-time-of-flight analysis in milk samples from FR50 and control rat dams. Milk analysis of FR50 rats demonstrated that maternal undernutrition decreases lactose concentration and modulates lipid profile at postnatal day 10 by increasing the unsaturated fatty acids/saturated fatty acids and diminishes serotransferrin levels at postnatal day 21. Our data indicate that maternal perinatal undernutrition modifies milk composition both quantitatively and qualitatively. These modifications by maternal nutrition open new perspectives to identify molecules that could be used in artificial milk to protect from the subsequent development of metabolic diseases. PMID:25550282

  14. Maternal perinatal undernutrition modifies lactose and serotranferrin in milk: relevance to the programming of metabolic diseases?

    PubMed

    Wattez, J S; Delmont, A; Bouvet, M; Beseme, O; Goers, S; Delahaye, F; Laborie, C; Lesage, J; Foligné, B; Breton, C; Metges, C C; Vieau, D; Pinet, F

    2015-03-01

    A close link between intrauterine growth restriction and development of chronic adult diseases such as obesity, diabetes, and hypertension has been established both in humans and animals. Modification of growth velocity during the early postnatal period (i.e., lactation) may also sensitize to the development of metabolic syndrome in adulthood. This suggests that milk composition may have long-lasting programming/deprogramming metabolic effects in the offspring. We therefore assess the effects of maternal perinatal denutrition on breast milk composition in a food-restricted 50% (FR50) rat model. Monosaccharides and fatty acids were characterized by gas chromatography, and proteins were profiled by surface-enhanced laser desorption/ionization-time-of-flight analysis in milk samples from FR50 and control rat dams. Milk analysis of FR50 rats demonstrated that maternal undernutrition decreases lactose concentration and modulates lipid profile at postnatal day 10 by increasing the unsaturated fatty acids/saturated fatty acids and diminishes serotransferrin levels at postnatal day 21. Our data indicate that maternal perinatal undernutrition modifies milk composition both quantitatively and qualitatively. These modifications by maternal nutrition open new perspectives to identify molecules that could be used in artificial milk to protect from the subsequent development of metabolic diseases.

  15. Early origin of adult renal disease.

    PubMed

    Maringhini, Silvio; Corrado, Ciro; Maringhini, Guido; Cusumano, Rosa; Azzolina, Vitalba; Leone, Francesco

    2010-10-01

    Observational studies in humans and experimental studies in animals have clearly shown that renal failure may start early in life. 'Fetal programming' is regulated by adaptations occurring in uterus including maternal nutrition, placental blood supply, and epigenetic changes. Low birth weight predisposes to hypertension and renal insufficiency. Congenital abnormalities of the kidney and urinary tract, adverse postnatal events, wrong nutritional habits may produce renal damage that will become clinically relevant in adulthood. Prevention should start early in children at risk of renal disease. PMID:20822331

  16. Prevalence of metabolic syndrome and its relationship with leisure time physical activity among Peruvian adults

    PubMed Central

    Gelaye, Bizu; Tafur, Luis Revilla; Lopez, Tania; Sanchez, Sixto; Williams, Michelle A.

    2009-01-01

    Background Metabolic syndrome (MetS) is an important risk factor of cardiovascular disease (CVD) and type 2 diabetes (T2DM). Previous studies have suggested an inverse relationship between physical activity and MetS. However, these findings were inconsistent; and few investigators have examined these associations among South Americans. We estimated the prevalence of MetS and its association with leisure time physical activity (LTPA) among Peruvian adults. Materials and methods This cross-sectional study of 1,675 individuals (619 men and 1056 women) was conducted among residents in Lima and Callao, Peru. Information about LTPA, socio-demographic, and other lifestyle characteristics were collected by interview. The presence of MetS was defined using the Adult Treatment Panel III (ATP III) criteria. Results Overall, the prevalence of MetS was 26.9% and was more common among women (29.9%) than men (21.6%). Habitual participation in LTPA was associated with a 23% reduced risk of MetS (OR=0.77; 95% CI: 0.60–1.03). There was an inverse trend of MetS risk with amount of LTPA (p=0.016). Compared with non-exercisers, those who exercised < 150 minutes/week had a 21% reduced risk of MetS (AOR= 0.79; 95% CI 0.60–1.04). Individuals who exercised ≥ 150 minutes/week, compared with non-exercisers, had a 42% reduced risk of MetS (AOR=0.58; 95% CI: 0.36–0.93). Associations of similar magnitudes were observed when men and women were studied separately. Conclusion These data document a high prevalence of MetS and suggest an association with LTPA among urban dwelling Peruvians. Further prospective studies are needed to confirm these observations and to examine interventions that may promote increased physical activity in this population. PMID:19563445

  17. Alterations in metabolic pathways and networks in Alzheimer's disease.

    PubMed

    Kaddurah-Daouk, R; Zhu, H; Sharma, S; Bogdanov, M; Rozen, S G; Matson, W; Oki, N O; Motsinger-Reif, A A; Churchill, E; Lei, Z; Appleby, D; Kling, M A; Trojanowski, J Q; Doraiswamy, P M; Arnold, S E

    2013-04-09

    The pathogenic mechanisms of Alzheimer's disease (AD) remain largely unknown and clinical trials have not demonstrated significant benefit. Biochemical characterization of AD and its prodromal phase may provide new diagnostic and therapeutic insights. We used targeted metabolomics platform to profile cerebrospinal fluid (CSF) from AD (n=40), mild cognitive impairment (MCI, n=36) and control (n=38) subjects; univariate and multivariate analyses to define between-group differences; and partial least square-discriminant analysis models to classify diagnostic groups using CSF metabolomic profiles. A partial correlation network was built to link metabolic markers, protein markers and disease severity. AD subjects had elevated methionine (MET), 5-hydroxyindoleacetic acid (5-HIAA), vanillylmandelic acid, xanthosine and glutathione versus controls. MCI subjects had elevated 5-HIAA, MET, hypoxanthine and other metabolites versus controls. Metabolite ratios revealed changes within tryptophan, MET and purine pathways. Initial pathway analyses identified steps in several pathways that appear altered in AD and MCI. A partial correlation network showed total tau most directly related to norepinephrine and purine pathways; amyloid-β (Ab42) was related directly to an unidentified metabolite and indirectly to 5-HIAA and MET. These findings indicate that MCI and AD are associated with an overlapping pattern of perturbations in tryptophan, tyrosine, MET and purine pathways, and suggest that profound biochemical alterations are linked to abnormal Ab42 and tau metabolism. Metabolomics provides powerful tools to map interlinked biochemical pathway perturbations and study AD as a disease of network failure.

  18. Sphingolipids in Obesity, Type 2 Diabetes, and Metabolic Disease

    PubMed Central

    Russo, S.B.; Ross, J.S.; Cowart, L.A.

    2014-01-01

    Metabolic disease, including obesity and type 2 diabetes, constitutes a major emerging health crisis in Western nations. Although the symptoms and clinical pathology and physiology of these conditions are well understood, the molecular mechanisms underlying the disease process have largely remained obscure. Sphingolipids, a lipid class with both signaling and structural properties, have recently emerged as key players in most major tissues affected by diabetes and are required components in the molecular etiology of this disease. Indeed, sphingolipids have been shown to mediate loss of insulin sensitivity, to promote the characteristic diabetic pro-inflammatory state, and to induce cell death and dysfunction in important organs such as the pancreas and heart. Furthermore, plasma sphingolipid levels are emerging as potential biomarkers for the decompensation of insulin resistance to frank type 2 diabetes. Despite these discoveries, the roles of specific sphingolipid species and sphingolipid metabolic pathways remain obscure, and newly developed experimental approaches must be employed to elucidate the detailed molecular mechanisms necessary for rational drug development and other clinical applications. PMID:23563667

  19. DIETARY HYPERGLYCEMIA, GLYCEMIC INDEX AND METABOLIC RETINAL DISEASES

    PubMed Central

    Chiu, Chung-Jung; Taylor, Allen

    2014-01-01

    The glycemic index (GI) indicates how fast blood glucose is raised after consuming a carbohydrate-containing food. Human metabolic studies indicate that GI is related to patho-physiological responses after meals. Compared with a low-GI meal, a high-GI meal is characterized with hyperglycemia during the early postprandial stage (0~2 h) and a compensatory hyperlipidemia associated with counter-regulatory hormone responses during late postprandial stage (4~6 h). Over the past three decades, several human health disorders have been related to GI. The strongest relationship suggests that consuming low-GI foods prevents diabetic complications. Diabetic retinopathy (DR) is a complication of diabetes. In this aspect, GI appears to be useful as a practical guideline to help diabetic people choose foods. Abundant epidemiological evidence also indicates positive associations between GI and risk for type 2 diabetes, cardiovascular disease, and more recently, age-related macular degeneration (AMD) in people without diabetes. Although data from randomized controlled intervention trials are scanty, these observations are strongly supported by evolving molecular mechanisms which explain the pathogenesis of hyperglycemia. This wide range of evidence implies that dietary hyperglycemia is etiologically related to human aging and diseases, including DR and AMD. In this context, these diseases can be considered metabolic retinal diseases. Molecular theories that explain hyperglycemic pathogenesis involve a mitochondria-associated pathway and four glycolysis-associated pathways, including advanced glycation end products formation, protein kinase C activation, polyol pathway, and hexosamine pathway. While the four glycolysis-associated pathways appear to be universal for both normoxic and hypoxic conditions, the mitochondria-associated mechanism appears to be most relevant to the hyperglycemic, normoxic pathogenesis. For diseases that affect tissues with highly active metabolism and that

  20. Dietary hyperglycemia, glycemic index and metabolic retinal diseases.

    PubMed

    Chiu, Chung-Jung; Taylor, Allen

    2011-01-01

    The glycemic index (GI) indicates how fast blood glucose is raised after consuming a carbohydrate-containing food. Human metabolic studies indicate that GI is related to patho-physiological responses after meals. Compared with a low-GI meal, a high-GI meal is characterized with hyperglycemia during the early postprandial stage (0-2h) and a compensatory hyperlipidemia associated with counter-regulatory hormone responses during late postprandial stage (4-6h). Over the past three decades, several human health disorders have been related to GI. The strongest relationship suggests that consuming low-GI foods prevents diabetic complications. Diabetic retinopathy (DR) is a complication of diabetes. In this aspect, GI appears to be useful as a practical guideline to help diabetic people choose foods. Abundant epidemiological evidence also indicates positive associations between GI and risk for type 2 diabetes, cardiovascular disease, and more recently, age-related macular degeneration (AMD) in people without diabetes. Although data from randomized controlled intervention trials are scanty, these observations are strongly supported by evolving molecular mechanisms which explain the pathogenesis of hyperglycemia. This wide range of evidence implies that dietary hyperglycemia is etiologically related to human aging and diseases, including DR and AMD. In this context, these diseases can be considered as metabolic retinal diseases. Molecular theories that explain hyperglycemic pathogenesis involve a mitochondria-associated pathway and four glycolysis-associated pathways, including advanced glycation end products formation, protein kinase C activation, polyol pathway, and hexosamine pathway. While the four glycolysis-associated pathways appear to be universal for both normoxic and hypoxic conditions, the mitochondria-associated mechanism appears to be most relevant to the hyperglycemic, normoxic pathogenesis. For diseases that affect tissues with highly active metabolism and

  1. Regional cerebral glucose metabolism is normal in young adults with Down syndrome

    SciTech Connect

    Schapiro, M.B.; Grady, C.L.; Kumar, A.; Herscovitch, P.; Haxby, J.V.; Moore, A.M.; White, B.; Friedland, R.P.; Rapoport, S.I. )

    1990-03-01

    Regional CMRglc (rCMRglc) values were measured with ({sup 18}F)2-fluoro-2-deoxy-D-glucose ({sup 18}FDG) and positron emission tomography (PET), using a Scanditronix PC-1024-7B scanner, in 14 healthy, noninstitutionalized subjects with trisomy 21 (Down syndrome; DS) (mean age 30.0 years, range 25-38 years) and in 13 sex-matched, healthy volunteers (mean age 29.5 years, range 22-38 years). In the DS group, mean mental age on the Peabody Picture Vocabulary Test was 7.8 years and dementia was not present. Resting rCMRglc was determined with eyes covered and ears occluded in a quiet, darkened room. Global gray CMRglc equaled 8.76 +/- 0.76 mg/100 g/min (mean +/- SD) in the DS group as compared with 8.74 +/- 1.19 mg/100 g/min in the control group (p greater than 0.05). Gray matter regional measurements also did not differ between groups. The ratio of rCMRglc to global CMRglc, calculated to reduce the variance associated with absolute rCMRglc, and right/left ratios did not show any consistent differences. These results show that healthy young DS adults do not have alterations in regional or global brain glucose metabolism, as measured with 18FDG and PET, prior to an age at which the neuropathological changes in Alzheimer disease are reported to occur.

  2. Transfer to Adult Care--Experiences of Young Adults with Congenital Heart Disease.

    PubMed

    Asp, Ann; Bratt, Ewa-Lena; Bramhagen, Ann-Cathrine

    2015-01-01

    More than 90% of children born with congenital heart disease survive into adulthood due to successes of cardiac surgery and medical management. Interviews with 16 young adults with congenital heart disease to explore their experiences of transfer from pediatric to adult care were performed. The analysis identified five themes; Feeling secure during the transfer process, Experiencing trust in the care, Expecting to be involved, Assuming responsibility for one's health is a process and Lack of knowledge leads to uncertainty. In conclusion; a structured and gradual transfer process was necessary to enable the informants to shoulder the responsibility for self-care.

  3. Emerging pathways in genetic Parkinson's disease: Potential role of ceramide metabolism in Lewy body disease.

    PubMed

    Bras, Jose; Singleton, Andrew; Cookson, Mark R; Hardy, John

    2008-12-01

    Heterozygous loss-of-function mutations at the glucosecerebrosidase locus have recently been shown to be a potent risk factor for Lewy body disease. Based on this observation, we have re-evaluated the likelihood that the different PARK loci (defined using clinical criteria for disease) may be misleading attempts to find common pathways to pathogenesis. Rather, we suggest, grouping the different loci which lead to different Lewy body disease may be more revealing. Doing this, we suggest that several of the genes involved in disparate Lewy body diseases impinge on ceramide metabolism and we suggest that this may be a common theme for pathogenesis. PMID:19021754

  4. Does acute caffeine ingestion alter brain metabolism in young adults?

    PubMed

    Xu, Feng; Liu, Peiying; Pekar, James J; Lu, Hanzhang

    2015-04-15

    Caffeine, as the most commonly used stimulant drug, improves vigilance and, in some cases, cognition. However, the exact effect of caffeine on brain activity has not been fully elucidated. Because caffeine has a pronounced vascular effect which is independent of any neural effects, many hemodynamics-based methods such as fMRI cannot be readily applied without a proper calibration. The scope of the present work is two-fold. In Study 1, we used a recently developed MRI technique to examine the time-dependent changes in whole-brain cerebral metabolic rate of oxygen (CMRO2) following the ingestion of 200mg caffeine. It was found that, despite a pronounced decrease in CBF (p<0.001), global CMRO2 did not change significantly. Instead, the oxygen extraction fraction (OEF) was significantly elevated (p=0.002) to fully compensate for the reduced blood supply. Using the whole-brain finding as a reference, we aim to investigate whether there are any regional differences in the brain's response to caffeine. Therefore, in Study 2, we examined regional heterogeneities in CBF changes following the same amount of caffeine ingestion. We found that posterior brain regions such as posterior cingulate cortex and superior temporal regions manifested a slower CBF reduction, whereas anterior brain regions including dorsolateral prefrontal cortex and medial frontal cortex showed a faster rate of decline. These findings have a few possible explanations. One is that caffeine may result in a region-dependent increase or decrease in brain activity, resulting in an unaltered average brain metabolic rate. The other is that caffeine's effect on vasculature may be region-specific. Plausibility of these explanations is discussed in the context of spatial distribution of the adenosine receptors.

  5. Does acute caffeine ingestion alter brain metabolism in young adults?

    PubMed

    Xu, Feng; Liu, Peiying; Pekar, James J; Lu, Hanzhang

    2015-04-15

    Caffeine, as the most commonly used stimulant drug, improves vigilance and, in some cases, cognition. However, the exact effect of caffeine on brain activity has not been fully elucidated. Because caffeine has a pronounced vascular effect which is independent of any neural effects, many hemodynamics-based methods such as fMRI cannot be readily applied without a proper calibration. The scope of the present work is two-fold. In Study 1, we used a recently developed MRI technique to examine the time-dependent changes in whole-brain cerebral metabolic rate of oxygen (CMRO2) following the ingestion of 200mg caffeine. It was found that, despite a pronounced decrease in CBF (p<0.001), global CMRO2 did not change significantly. Instead, the oxygen extraction fraction (OEF) was significantly elevated (p=0.002) to fully compensate for the reduced blood supply. Using the whole-brain finding as a reference, we aim to investigate whether there are any regional differences in the brain's response to caffeine. Therefore, in Study 2, we examined regional heterogeneities in CBF changes following the same amount of caffeine ingestion. We found that posterior brain regions such as posterior cingulate cortex and superior temporal regions manifested a slower CBF reduction, whereas anterior brain regions including dorsolateral prefrontal cortex and medial frontal cortex showed a faster rate of decline. These findings have a few possible explanations. One is that caffeine may result in a region-dependent increase or decrease in brain activity, resulting in an unaltered average brain metabolic rate. The other is that caffeine's effect on vasculature may be region-specific. Plausibility of these explanations is discussed in the context of spatial distribution of the adenosine receptors. PMID:25644657

  6. Does acute caffeine ingestion alter brain metabolism in young adults?

    PubMed Central

    Xu, Feng; Liu, Peiying; Pekar, James J.; Lu, Hanzhang

    2015-01-01

    Caffeine, as the most commonly used stimulant drug, improves vigilance and, in some cases, cognition. However, the exact effect of caffeine on brain activity has not been fully elucidated. Because caffeine has a pronounced vascular effect which is independent of any neural effects, many hemodynamics-based methods such as fMRI cannot be readily applied without a proper calibration. The scope of the present work is two-fold. In Study 1, we used a recently developed MRI technique to examine the time-dependent changes in whole-brain cerebral metabolic rate of oxygen (CMRO2) following the ingestion of 200mg caffeine. It was found that, despite a pronounced decrease in CBF (p<0.001), global CMRO2 did not change significantly. Instead, the oxygen extraction fraction (OEF) was significantly elevated (p=0.002) to fully compensate for the reduced blood supply. Using the whole-brain finding as a reference, we aim to investigate whether there are any regional differences in the brain’s response to caffeine. Therefore, in Study 2, we examined regional heterogeneities in CBF changes following the same amount of caffeine ingestion. We found that posterior brain regions such as posterior cingulate cortex and superior temporal regions manifested a slower CBF reduction, whereas anterior brain regions including dorsolateral prefrontal cortex and medial frontal cortex showed a faster rate of decline. These findings have a few possible explanations. One is that caffeine may result in a region-dependent increase or decrease in brain activity, resulting in an unaltered average brain metabolic rate. The other is that caffeine’s effect on vasculature may be region-specific. Plausibility of these explanations is discussed in the context of spatial distribution of the adenosine receptors. PMID:25644657

  7. Plasma levels of inflammatory cytokines in adult Nigerians with the metabolic syndrome

    PubMed Central

    Christiana, Udenze Ifeoma; Casimir, Amadi E.; Nicholas, Awolola Awodele; Christian, Makwe C.; Obiefuna, Ajie I.

    2016-01-01

    Background: The aim of this study is to determine the plasma levels of interleukin 6 (IL-6), tumor necrotic factor alpha (TNF-α, and C-reactive protein (CRP) in adult Nigerians with the metabolic syndrome and to determine the relationship between components of the metabolic syndrome and CRP in adult Nigerians. Subjects and Methods: This was a case–control study of fifty adult men and women with the metabolic syndrome, and fifty age- and sex-matched males and females without the metabolic syndrome. Metabolic syndrome was defined based on the National Cholesterol Education Programme-Adult Treatment Panel III criteria. Written informed consent was obtained from the participants. Blood pressure and anthropometry measurements were taken and venous blood was collected after an overnight fast. The Ethics Committee of the Lagos University Teaching Hospital, Lagos, Nigeria, approved the study protocol. Comparisons of continuous variables and categorical variables were done using the Student's t-test and Chi-square test, respectively. Regression analysis was used to determine the associations between variables. Statistical significance was set at P< 0.05. Results: The age- and sex-matched males and females with and without the metabolic syndrome did not differ in their sociodemographic characteristics. They however differed in some clinical and laboratory parameters such as diastolic blood pressure (P = 0.048), waist circumference (P = 0.002), body mass index (P = 0.012), waist/hip ratio (P = 0.023), high density lipoprotein (HDL) (P = 0.012), and insulin resistance (IR) (P = 0.042). There was a statistically significant increase in the inflammatory marker, CRP (P = 0.019), the cytokines, IL6 (P = 0.040), and TNF-α (P = 0.031) between the subjects with and without metabolic syndrome. There was also a significant association between CRP, waist circumference, IR, and HDL in the metabolic syndrome (P < 0.05). Conclusion: Plasma levels of inflammatory cytokines are raised in

  8. Histone methylations in heart development, congenital and adult heart diseases.

    PubMed

    Zhang, Qing-Jun; Liu, Zhi-Ping

    2015-01-01

    Heart development comprises myocyte specification, differentiation and cardiac morphogenesis. These processes are regulated by a group of core cardiac transcription factors in a coordinated temporal and spatial manner. Histone methylation is an emerging epigenetic mechanism for regulating gene transcription. Interplay among cardiac transcription factors and histone lysine modifiers plays important role in heart development. Aberrant expression and mutation of the histone lysine modifiers during development and in adult life can cause either embryonic lethality or congenital heart diseases, and influences the response of adult hearts to pathological stresses. In this review, we describe current body of literature on the role of several common histone methylations and their modifying enzymes in heart development, congenital and adult heart diseases.

  9. Histone methylations in heart development, congenital and adult heart diseases

    PubMed Central

    Zhang, Qing-Jun; Liu, Zhi-Ping

    2015-01-01

    Heart development comprises myocyte specification, differentiation and cardiac morphogenesis. These processes are regulated by a group of core cardiac transcription factors in a coordinated temporal and spatial manner. Histone methylation is an emerging epigenetic mechanism for regulating gene transcription. Interplay among cardiac transcription factors and histone lysine modifiers plays important role in heart development. Aberrant expression and mutation of the histone lysine modifiers during development and in adult life can cause either embryonic lethality or congenital heart diseases, and influences the response of adult hearts to pathological stresses. In this review, we describe current body of literature on the role of several common histone methylations and their modifying enzymes in heart development, congenital and adult heart diseases. PMID:25942538

  10. Influence of temperature and activity on the metabolic rate of adult Drosophila melanogaster.

    PubMed

    Berrigan, D; Partridge, L

    1997-12-01

    We measured metabolic rates of adult male Drosophila melanogaster allowed to evolve in the laboratory at 18 and 25 degrees C and compared these with measurements of metabolic rates of flies collected along a latitudinal gradient in Australia. Metabolic rates of flies that had evolved in the laboratory at low temperature were 5-7% higher than those of flies allowed to evolve at high temperature. Metabolic rates of field collected increased with latitude when measured at 18 degrees C but not at higher temperature (25 degrees C) and were about 9% greater in high latitude (approximately 41'00) flies than low latitude (16'53) flies. Metabolic rate was strongly influenced by measurement temperature; estimated Q10s ranged from 1.79 to 2.5 for measurements made at 18 and 25 degrees C. Metabolic rate scaled isometrically with body mass; the estimated slope of a ln-ln regression of metabolic rate and body mass was 1.03 +/- 0.1. We used our measures of metabolic rate and activity to estimate the minimum cost of transport (MCOT) while walking. The estimates of MCOT have high standard errors (lab, 34.30 +/- 14.2 ml O2/g/km; and field, 38.0 +/- 17.0 ml O2/g/km); however, they differ by only 3-9% from predicted values based on allometric relationships reported in the literature.

  11. Diphosphonates in the evaluation of metabolic bone disease.

    PubMed

    Fogelman, I; Smith, M L

    1982-03-01

    The bone scan may be of value in the assessment of patients with metabolic bone disease. However the superiority of the bone scan when compared to radiology in conditions such as renal osteodystrophy, osteomalacia, primary hyperparathyroidism, and osteoporosis requires substantiation with the newer radiopharmaceuticals which have a higher affinity for bone. Two methods of quantitating skeletal uptake of tracer have been assessed to try to remove the subjective aspect of bone scan evaluation. Measurements of bone to soft tissue ratios have proved clinically disappointing, but 24 hour whole body retention of diphosphonate appears to provide a sensitive index of increased bone turnover.

  12. Cardiovascular Disease Risk Factors among Emerging Adults in College

    ERIC Educational Resources Information Center

    Abshire, Demetrius Alexander

    2014-01-01

    The purpose of this dissertation was to examine factors associated with cardiovascular disease (CVD) risk among emerging adults in college aged 18-25 years. CVD risks that develop during this period often persist into adulthood making it an ideal time to target CVD prevention. The specific aims of this dissertation were to 1) explore perceptions…

  13. Degeneration of Dopaminergic Neurons Due to Metabolic Alterations and Parkinson’s Disease

    PubMed Central

    Song, Juhyun; Kim, Jongpil

    2016-01-01

    The rates of metabolic diseases, such as type 2 diabetes mellitus (T2DM), obesity, and cardiovascular disease (CVD), markedly increase with age. In recent years, studies have reported an association between metabolic changes and various pathophysiological mechanisms in the central nervous system (CNS) in patients with metabolic diseases. Oxidative stress and hyperglycemia in metabolic diseases lead to adverse neurophysiological phenomena, including neuronal loss, synaptic dysfunction, and improper insulin signaling, resulting in Parkinson’s disease (PD). In addition, several lines of evidence suggest that alterations of CNS environments by metabolic changes influence the dopamine neuronal loss, eventually affecting the pathogenesis of PD. Thus, we reviewed recent findings relating to degeneration of dopaminergic neurons during metabolic diseases. We highlight the fact that using a metabolic approach to manipulate degeneration of dopaminergic neurons can serve as a therapeutic strategy to attenuate pathology of PD. PMID:27065205

  14. Relationship between chronic kidney disease and metabolic syndrome: current perspectives

    PubMed Central

    Nashar, Khaled; Egan, Brent M

    2014-01-01

    Both metabolic syndrome (MetS) and chronic kidney disease (CKD) are increasing in incidence and lead to significant cardiovascular morbidity and mortality. The relationship between these two entities is complex. Individual components of the MetS are known risk factors for incident kidney disease, but it is not clear how the clustering of these components is linked to the development and progression of kidney disease. Cross-sectional studies show an association of the MetS and prevalent CKD; however, one cannot draw conclusions as to which came first – the MetS or the kidney disease. Observational studies suggest a relationship between MetS and incident CKD, but they also demonstrate the development of MetS in patients with established CKD. These observations suggest a bidirectional relationship. A better understanding of the relationship between components of the MetS and whether and how these components contribute to progression of CKD and incident cardiovascular disease could inform more effective prevention strategies. PMID:25258547

  15. Pathophysiology and therapeutics of cardiovascular disease in metabolic syndrome.

    PubMed

    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.

  16. Metabolic bone disease in chronic renal failure. I. Dialyzed uremics.

    PubMed Central

    Huffer, W. E.; Kuzela, D.; Popovtzer, M. M.

    1975-01-01

    Garner and ball's point counting technic was used to compare metabolic bone disease in dialyzed and nondialyzed uremic patients. Histologic measurements of bone from dialyzed and nondialyzed uremic patients dying between 1966 and 1971 showed that dialyzed patients have quantitatively more severe bone resorption, distortion of trabecular architecture and mineralization defects. Mineralization defects become more severe as the duration of dialysis increases but are not related to serum calcium and phosphorus levels. Bone volume in both groups is normal or increased and in dialysis patients increases in proportion to the elevation of serum phosphorus. Mean serum phosphorus and calcium levels, bone volume, and volume: surface ratios all decreased in dialysis patients between 1966 and 1971, while bone resorption and mineralization defects did not change. These results suggest that lowering of serum phosphorus without increasing serum calcium may aggrevate the uremic bone disease by reducing bone volume without improvement of mineralization and resorption defects. Images Fig 1 PMID:1119535

  17. [Metabolic syndrome in coronary artery and occlusive vascular diseases: a systematic review].

    PubMed

    Farias, Daniela Reis Elbert; Pereira, Avany Fernandes; Rosa, Glorimar

    2010-06-01

    Nowadays, the metabolic syndrome (MS) is highly prevalent and is associated with risk factors for non-transmissible chronic diseases, such as type 2 diabetes mellitus, and coronary atherosclerotic disease. The objective of this systematic review is to describe the results of studies that investigated the association of MS with coronary artery disease and occlusive vascular diseases. We conducted a systematic review of data from original studies published between 1999 and 2008, written in English or Portuguese, using the databases Medline, Pubmed, Science Direct and HighWire Press. We included articles in which the diagnosis of MS was made by the criteria of the National Cholesterol Education Program - Adult Treatment Panel III (NCEP ATP III, 2001). We excluded studies with animals, supplementation studies, and those with oral or intravenous administration of any substance, as well as those of low methodological quality and those which had a heterogeneous initial sample. Despite the heterogeneity among studies, we observed that individuals with MS had a higher probability (risk = 2.13) of developing occlusive vascular diseases, coronary disease, diabetes and stroke. Lifestyle changes such as healthy eating habits, regular physical activity and cessation of smoking should be encouraged by health professionals to minimize the complications and morbidity associated with MS.

  18. Dietary pattern and metabolic syndrome in thai adults.

    PubMed

    Aekplakorn, W; Satheannoppakao, W; Putwatana, P; Taneepanichskul, S; Kessomboon, P; Chongsuvivatwong, V; Chariyalertsak, S

    2015-01-01

    Objectives. To determine the dietary patterns of middle-aged Thais and their association with metabolic syndrome (MetS). Methods. The Thai National Health Examination Survey IV data of 5,872 participants aged ≥30-59 years were used. Dietary patterns were obtained by factor analysis and their associations with Mets were examined using multiple logistic regression. Results. Three major dietary patterns were identified. The first, meat pattern, was characterized by a high intake of red meat, processed meat, and fried food. The second, healthy pattern, equated to a high intake of beans, vegetables, wheat, and dairy products. The third, high carbohydrate pattern, had a high intake of glutinous rice, fermented fish, chili paste, and bamboo shoots. Respondents with a healthy pattern were more likely to be female, higher educated, and urban residents. The carbohydrate pattern was more common in the northeast and rural areas. Compared with the lowest quartile, the highest quartile of carbohydrate pattern was associated with MetS (adjusted odds ratio: 1.82; 95% CI 1.31, 2.55 in men and 1.60; 95% CI 1.24, 2.08 in women), particularly among those with a low level of leisure time physical activity (LTPA). Conclusion. The carbohydrate pattern with low level of LTPA increased the odds of MetS. PMID:25699190

  19. Bariatric surgery for obesity and metabolic conditions in adults.

    PubMed

    Arterburn, David E; Courcoulas, Anita P

    2014-08-27

    This review summarizes recent evidence related to the safety, efficacy, and metabolic outcomes of bariatric surgery to guide clinical decision making. Several short term randomized controlled trials have demonstrated the effectiveness of bariatric procedures for inducing weight loss and initial remission of type 2 diabetes. Observational studies have linked bariatric procedures with long term improvements in body weight, type 2 diabetes, survival, cardiovascular events, incident cancer, and quality of life. Perioperative mortality for the average patient is low but varies greatly across subgroups. The incidence of major complications after surgery also varies widely, and emerging data show that some procedures are associated with a greater risk of substance misuse disorders, suicide, and nutritional deficiencies. More research is needed to enable long term outcomes to be compared across various procedures and subpopulations, and to identify those most likely to benefit from surgical intervention. Given uncertainties about the balance between the risks and benefits of bariatric surgery in the long term, the decision to undergo surgery should be based on a high quality shared decision making process.

  20. Bariatric surgery for obesity and metabolic conditions in adults

    PubMed Central

    Courcoulas, Anita P

    2014-01-01

    This review summarizes recent evidence related to the safety, efficacy, and metabolic outcomes of bariatric surgery to guide clinical decision making. Several short term randomized controlled trials have demonstrated the effectiveness of bariatric procedures for inducing weight loss and initial remission of type 2 diabetes. Observational studies have linked bariatric procedures with long term improvements in body weight, type 2 diabetes, survival, cardiovascular events, incident cancer, and quality of life. Perioperative mortality for the average patient is low but varies greatly across subgroups. The incidence of major complications after surgery also varies widely, and emerging data show that some procedures are associated with a greater risk of substance misuse disorders, suicide, and nutritional deficiencies. More research is needed to enable long term outcomes to be compared across various procedures and subpopulations, and to identify those most likely to benefit from surgical intervention. Given uncertainties about the balance between the risks and benefits of bariatric surgery in the long term, the decision to undergo surgery should be based on a high quality shared decision making process. PMID:25164369

  1. Imaging of acquired coronary diseases: From children to adults.

    PubMed

    Dehaene, A; Jacquier, A; Falque, C; Gorincour, G; Gaubert, J Y

    2016-05-01

    Acquired coronary diseases include aneurysms, fistulae, dissections, and stenosis. Aneurysms may occur secondarily to Kawasaki disease, a childhood vasculitis, the prognosis of which depends on the coronary involvement, or they may be degenerative, infectious, inflammatory, or traumatic in origin. Fistulae develop between the coronary arterial system and a pulmonary or bronchial artery, or cardiac cavity. Dissections may occur spontaneously or may be post-traumatic. These coronary abnormalities may be found incidentally or may present as complications, infarction or rupture. The goals of this article are to understand acquired childhood and adult coronary diseases and their usual means of presentation, the ways of investigating them, and the principles of their treatment. PMID:27130480

  2. Adult-Onset Still's Disease: From Pathophysiology to Targeted Therapies

    PubMed Central

    Mavragani, Clio P.; Spyridakis, Evangelos G.; Koutsilieris, Michael

    2012-01-01

    Adult-onset Still's disease (AOSD) is a systemic inflammatory disorder affecting primarily young individuals. The diagnosis is primarily clinical and necessitates the exclusion of a wide range of mimicking disorders. Given the lack of solid data in regard to the underlying pathogenetic mechanisms, treatment of AOSD has been for years largely empirical. Recent advances have revealed a pivotal role of several proinflammatory cytokines such as tumor necrosis factor-α (TNF-α), interleukin-1 (IL-1), interleukin-6 (IL-6), interleukin-8 (IL-8), and interleukin-18 (IL-18) in disease pathogenesis, giving rise to the development of new targeted therapies aiming at optimal disease control. PMID:22792508

  3. Association of cigarette smoking and metabolic syndrome in a Puerto Rican adult population.

    PubMed

    Calo, William A; Ortiz, Ana P; Suárez, Erick; Guzmán, Manuel; Pérez, Carmen M; Pérez, Cynthia M

    2013-08-01

    Metabolic syndrome (MetSyn) is related to an increased risk for type 2 diabetes and cardiovascular disease. Smokers are at greater risk than nonsmokers of becoming insulin resistant and to develop cardiovascular disease. This study aimed to explore the association between cigarette smoking, MetSyn and its components among Puerto Rican adults. A representative sample of 856 persons aged 21-79 years from the San Juan Metropolitan area participated in this study. Demographic and lifestyle characteristics, including smoking habits, were gathered from a self-reported questionnaire. MetSyn was defined according to the revised NCEP-ATP III criteria and measured using biochemical measurements and anthropometric indices. Logistic regression models were used to estimate prevalence odds ratios (POR) and its 95 % confidence intervals (CI). MetSyn was significantly (P < 0.001) more prevalent in former smokers (48.4 %) as compared to current (42.7 %) and never smokers (40.0 %). However, after adjusting for possible confounders, current smokers who used more than 20 cigarettes per day were 2.24 (95 % CI = 1.00-4.99) times more likely to have MetSyn as compared to never smokers. Heavy smokers were also more likely to have high triglyceride levels (POR = 2.22, 95 % CI = 1.12-4.38) and low HDL-cholesterol levels (POR = 2.49, 95 % CI = 1.28-4.86) as compared to never smokers. This study supports previous reports of an increased risk of MetSyn among current smokers, particularly those with a heavier consumption. Tobacco control strategies, such as preventing smoking initiation and disseminating evidence-based cessation programs, are necessary to reduce the burden of MetSyn in Puerto Rico.

  4. The microvasculature: a target for nutritional programming and later risk of cardio-metabolic disease.

    PubMed

    Musa, M G; Torrens, C; Clough, G F

    2014-01-01

    There is compelling evidence that microvascular deficits affecting multiple tissues and organs play an important role in the aetiopathogenesis of cardio-metabolic disease. Furthermore, both in humans and animal models, deficits in small vessel structure and function can be detected early, often before the onset of macrovascular disease and the development of end-organ damage that is common to hypertension and obesity-associated clinical disorders. This article considers the growing evidence for the negative impact of an adverse maternal diet on the long-term health of her child, and how this can result in a disadvantageous vascular phenotype that extends to the microvascular bed. We describe how structural and functional modifications in the offspring microcirculation during development may represent an important and additional risk determinant to increase susceptibility to the development of cardio-metabolic disease in adult life and consider the cell-signalling pathways associated with endothelial dysfunction that may be 'primed' by the maternal environment. Published studies were identified that reported outcomes related to the microcirculation, endothelium, maternal diet and vascular programming using NCBI PubMed.gov, MEDLINE and ISI Web of Science databases from 1980 until April 2013 using pre-specified search terms. Information extracted from over 230 original reports and review articles was critically evaluated by the authors for inclusion in this review.

  5. Omega-3 fatty acids: role in metabolism and cardiovascular disease.

    PubMed

    Gerber, Philipp A; Gouni-Berthold, Ioanna; Berneis, Kaspar

    2013-01-01

    The inverse association of cardiovascular risk with intake of omega-3 polyunsaturated fatty acids was suspected early in populations that are known to have a high consumption of fish and fish oil. Subsequent cohort studies confirmed such associations in other populations. Further evidence of possible beneficial effects on metabolism and cardiovascular health was provided by many studies that were able to show specific mechanisms that may underlie these observations. These include improvement of the function of tissues involved in the alterations occurring during the development of obesity and the metabolic syndrome, as adipose tissue, the liver and skeletal muscle. Direct action on the cardiovascular system was not only shown regarding vascular function and the formation of atherosclerotic plaques, but also by providing antiarrhythmic effects on the heart. Data on these effects come from in vitro as well as in vivo studies that were conducted in animal models of disease, in healthy humans and in humans suffering from cardiovascular disease. To define prophylactic as well as treatment options in primary and secondary prevention, large clinical trial assessed the effect of omega-3 polyunsaturated fatty acids on end points as cardiovascular morbidity and mortality. However, so far these trials provided ambiguous data that do allow recommendations regarding the use of omega-3 polyunsaturated fatty acids in higher dosages and beyond the dietary advice of regular fish intake only in few clinical situations, such as severe hypertriglyceridemia.

  6. Adipokines in Healthy Skeletal Muscle and Metabolic Disease.

    PubMed

    Coles, C A

    2016-01-01

    Adipose tissue not only functions as a reserve to store energy but has become of major interest as an endocrine organ, releasing signalling molecules termed adipokines which impact on other tissues, such as skeletal muscle. Adipocytes, within skeletal muscle and adipose tissue, secrete adipokines to finely maintain the balance between feed intake and energy expenditure. This book chapter focuses on the three adipokines, adiponectin, leptin and IL-6, which have potent effects on skeletal muscle during rest and exercise. Similarly, adiponectin, leptin and IL-6 enhance glucose uptake and increase fatty acid oxidation in skeletal muscle. Fatty acid oxidation is increased through activation of AMPK (adenosine monophosphate-activated protein kinase signalling) causing phosphorylation and inhibition of ACC (acetyl-coenzyme A carboxylase), decreasing availability of malonyl CoA. Leptin and adiponectin also control feed intake via AMPK signalling in the hypothalamus. Adipokines function to maintain energy homeostasis, however, when feed intake exceeds energy expenditure adipokines can become dysregulated causing lipotoxicity in skeletal muscle and metabolic disease can prevail. Cross-talk between adipocytes and skeletal muscle via correct control by adipokines is important in controlling energy homeostasis during rest and exercise and can help prevent metabolic disease. PMID:27003399

  7. Epicardial adipose tissue in endocrine and metabolic diseases.

    PubMed

    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.

  8. Understanding the role of gut microbiome in metabolic disease risk.

    PubMed

    Sanz, Yolanda; Olivares, Marta; Moya-Pérez, Ángela; Agostoni, Carlo

    2015-01-01

    The gut microbiota structure, dynamics, and function result from interactions with environmental and host factors, which jointly influence the communication between the gut and peripheral tissues, thereby contributing to health programming and disease risk. Incidence of both type-1 and type-2 diabetes has increased during the past decades, suggesting that there have been changes in the interactions between predisposing genetic and environmental factors. Animal studies show that gut microbiota and its genome (microbiome) influence alterations in energy balance (increased energy harvest) and immunity (inflammation and autoimmunity), leading to metabolic dysfunction (e.g., insulin resistance and deficiency). Thus, although they have different origins, both disorders are linked by the association of the gut microbiota with the immune-metabolic axis. Human studies have also revealed shifts in microbiome signatures in diseased subjects as compared with controls, and a few of them precede the development of these disorders. These studies contribute to pinpointing specific microbiome components and functions (e.g., butyrate-producing bacteria) that can protect against both disorders. These could exert protective roles by strengthening gut barrier function and regulating inflammation, as alterations in these are a pathophysiological feature of both disorders, constituting common targets for future preventive approaches.

  9. Roles of leptin in bone metabolism and bone diseases.

    PubMed

    Chen, Xu Xu; Yang, Tianfu

    2015-09-01

    Adipose tissue has been more accepted as an active contributor to whole body homeostasis, rather than just a fat depot, since leptin, a 16 kDa protein, was discovered as the product of the obese gene in 1994. With more and more studies conducted on this hormone, it has been shown that there is a close relationship between adipose tissue and bone, which have important effects on each other. Bone is the source of many hormones, such as osteocalcin, that can affect energy metabolism and then the anabolism or catabolism of fat tissue. In contrast, the adipose tissue synthesizes and releases a series of adipokines, which are involved in bone metabolism through direct or indirect effects on bone formation and resorption. Interestingly, leptin, one of the most important cytokines derived from fat tissue, seems to account for the largest part of effects on bone, through direct or indirect involvement in bone remodeling and by playing a significant role in many bone diseases, such as osteoporosis, osteoarthritis, rheumatic arthritis, bone tumors and even fractures. In this review, we will discuss the progress in leptin research, particularly focusing on the roles of leptin in bone diseases.

  10. NAD+ metabolism, a therapeutic target for age-related metabolic disease

    PubMed Central

    Auwerx, Johan

    2013-01-01

    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 Sir2, the founding member of the sirtuin protein family, as being NAD+-dependent reignited interest in this metabolite. The sirtuins (SIRT1-7 in mammals) utilize NAD+ to deacetylate proteins in different subcellular compartments with a variety of functions, but with a strong convergence on optimizing mitochondrial function. Since cellular NAD+ levels are limiting for sirtuin activity, boosting its levels is a powerful means to activate sirtuins as a potential therapy for mitochondrial, often age-related, diseases. Indeed, supplying excess precursors, or blocking its utilization by PARP enzymes or CD38/CD157, boosts NAD+ levels, activates sirtuins and promotes healthy aging. Here, we discuss the current state of knowledge of NAD+ metabolism, primarily in relation to sirtuin function. We highlight how NAD+ levels change in diverse physiological conditions, and how this can be employed as a pharmacological strategy. PMID:23742622

  11. Pathogenesis of alcoholic liver disease: Role of oxidative metabolism

    PubMed Central

    Ceni, Elisabetta; Mello, Tommaso; Galli, Andrea

    2014-01-01

    Alcohol consumption is a predominant etiological factor in the pathogenesis of chronic liver diseases, resulting in fatty liver, alcoholic hepatitis, fibrosis/cirrhosis, and hepatocellular carcinoma (HCC). Although the pathogenesis of alcoholic liver disease (ALD) involves complex and still unclear biological processes, the oxidative metabolites of ethanol such as acetaldehyde and reactive oxygen species (ROS) play a preeminent role in the clinical and pathological spectrum of ALD. Ethanol oxidative metabolism influences intracellular signaling pathways and deranges the transcriptional control of several genes, leading to fat accumulation, fibrogenesis and activation of innate and adaptive immunity. Acetaldehyde is known to be toxic to the liver and alters lipid homeostasis, decreasing peroxisome proliferator-activated receptors and increasing sterol regulatory element binding protein activity via an AMP-activated protein kinase (AMPK)-dependent mechanism. AMPK activation by ROS modulates autophagy, which has an important role in removing lipid droplets. Acetaldehyde and aldehydes generated from lipid peroxidation induce collagen synthesis by their ability to form protein adducts that activate transforming-growth-factor-β-dependent and independent profibrogenic pathways in activated hepatic stellate cells (HSCs). Furthermore, activation of innate and adaptive immunity in response to ethanol metabolism plays a key role in the development and progression of ALD. Acetaldehyde alters the intestinal barrier and promote lipopolysaccharide (LPS) translocation by disrupting tight and adherent junctions in human colonic mucosa. Acetaldehyde and LPS induce Kupffer cells to release ROS and proinflammatory cytokines and chemokines that contribute to neutrophils infiltration. In addition, alcohol consumption inhibits natural killer cells that are cytotoxic to HSCs and thus have an important antifibrotic function in the liver. Ethanol metabolism may also interfere with cell

  12. Sleep deficits but no metabolic deficits in premanifest Huntington's disease

    PubMed Central

    Panin, Francesca; Goodman, Anna O. G.; Lazic, Stanley E.; Lazar, Zsolt I.; Mason, Sarah L.; Rogers, Lorraine; Murgatroyd, Peter R.; Watson, Laura P. E.; Singh, Priya; Borowsky, Beth; Shneerson, John M.; Barker, Roger A.

    2015-01-01

    Objective Huntington disease (HD) is a fatal autosomal dominant, neurodegenerative condition characterized by progressively worsening motor and nonmotor problems including cognitive and neuropsychiatric disturbances, along with sleep abnormalities and weight loss. However, it is not known whether sleep disturbances and metabolic abnormalities underlying the weight loss are present at a premanifest stage. Methods We performed a comprehensive sleep and metabolic study in 38 premanifest gene carrier individuals and 36 age‐ and sex‐matched controls. The study consisted of 2 weeks of actigraphy at home, 2 nights of polysomnography and multiple sleep latency tests in the laboratory, and body composition assessment using dual energy x‐ray absorptiometry scanning with energy expenditure measured over 10 days at home by doubly labeled water and for 36 hours in the laboratory by indirect calorimetry along with detailed cognitive and clinical assessments. We performed a principal component analyses across all measures within each studied domain. Results Compared to controls, premanifest gene carriers had more disrupted sleep, which was best characterized by a fragmented sleep profile. These abnormalities, as well as a theta power (4–7Hz) decrease in rapid eye movement sleep, were associated with disease burden score. Objectively measured sleep problems coincided with the development of cognitive, affective, and subtle motor deficits and were not associated with any metabolic alterations. Interpretation The results show that among the earliest abnormalities in premanifest HD is sleep disturbances. This raises questions as to where the pathology in HD begins and also whether it could drive some of the early features and even possibly the pathology. Ann Neurol 2015;78:630–648 PMID:26224419

  13. New loci associated with birth weight identify genetic links between intrauterine growth and adult height and metabolism

    PubMed Central

    Horikoshi, Momoko; Yaghootkar, Hanieh; Mook-Kanamori, Dennis O.; Sovio, Ulla; Taal, H. Rob; Hennig, Branwen J.; Bradfield, Jonathan P.; St. Pourcain, Beate; Evans, David M.; Charoen, Pimphen; Kaakinen, Marika; Cousminer, Diana L.; Lehtimäki, Terho; Kreiner-Møller, Eskil; Warrington, Nicole M.; Bustamante, Mariona; Feenstra, Bjarke; Berry, Diane J.; Thiering, Elisabeth; Pfab, Thiemo; Barton, Sheila J.; Shields, Beverley M.; Kerkhof, Marjan; van Leeuwen, Elisabeth M.; Fulford, Anthony J.; Kutalik, Zoltán; Zhao, Jing Hua; den Hoed, Marcel; Mahajan, Anubha; Lindi, Virpi; Goh, Liang-Kee; Hottenga, Jouke-Jan; Wu, Ying; Raitakari, Olli T.; Harder, Marie N.; Meirhaeghe, Aline; Ntalla, Ioanna; Salem, Rany M.; Jameson, Karen A.; Zhou, Kaixin; Monies, Dorota M.; Lagou, Vasiliki; Kirin, Mirna; Heikkinen, Jani; Adair, Linda S.; Alkuraya, Fowzan S.; Al-Odaib, Ali; Amouyel, Philippe; Andersson, Ehm Astrid; Bennett, Amanda J.; Blakemore, Alexandra I.F.; Buxton, Jessica L.; Dallongeville, Jean; Das, Shikta; de Geus, Eco J. C.; Estivill, Xavier; Flexeder, Claudia; Froguel, Philippe; Geller, Frank; Godfrey, Keith M.; Gottrand, Frédéric; Groves, Christopher J.; Hansen, Torben; Hirschhorn, Joel N.; Hofman, Albert; Hollegaard, Mads V.; Hougaard, David M.; Hyppönen, Elina; Inskip, Hazel M.; Isaacs, Aaron; Jørgensen, Torben; Kanaka-Gantenbein, Christina; Kemp, John P.; Kiess, Wieland; Kilpeläinen, Tuomas O.; Klopp, Norman; Knight, Bridget A.; Kuzawa, Christopher W.; McMahon, George; Newnham, John P.; Niinikoski, Harri; Oostra, Ben A.; Pedersen, Louise; Postma, Dirkje S.; Ring, Susan M.; Rivadeneira, Fernando; Robertson, Neil R.; Sebert, Sylvain; Simell, Olli; Slowinski, Torsten; Tiesler, Carla M.T.; Tönjes, Anke; Vaag, Allan; Viikari, Jorma S.; Vink, Jacqueline M.; Vissing, Nadja Hawwa; Wareham, Nicholas J.; Willemsen, Gonneke; Witte, Daniel R.; Zhang, Haitao; Zhao, Jianhua; Wilson, James F.; Stumvoll, Michael; Prentice, Andrew M.; Meyer, Brian F.; Pearson, Ewan R.; Boreham, Colin A.G.; Cooper, Cyrus; Gillman, Matthew W.; Dedoussis, George V.; Moreno, Luis A; Pedersen, Oluf; Saarinen, Maiju; Mohlke, Karen L.; Boomsma, Dorret I.; Saw, Seang-Mei; Lakka, Timo A.; Körner, Antje; Loos, Ruth J.F.; Ong, Ken K.; Vollenweider, Peter; van Duijn, Cornelia M.; Koppelman, Gerard H.; Hattersley, Andrew T.; Holloway, John W.; Hocher, Berthold; Heinrich, Joachim; Power, Chris; Melbye, Mads; Guxens, Mònica; Pennell, Craig E.; Bønnelykke, Klaus; Bisgaard, Hans; Eriksson, Johan G.; Widén, Elisabeth; Hakonarson, Hakon; Uitterlinden, André G.; Pouta, Anneli; Lawlor, Debbie A.; Smith, George Davey; Frayling, Timothy M.; McCarthy, Mark I.; Grant, Struan F.A.; Jaddoe, Vincent W.V.; Jarvelin, Marjo-Riitta; Timpson, Nicholas J.; Prokopenko, Inga; Freathy, Rachel M.

    2012-01-01

    Birth weight within the normal range is associated with a variety of adult-onset diseases, but the mechanisms behind these associations are poorly understood1. Previous genome-wide association studies identified a variant in the ADCY5 gene associated both with birth weight and type 2 diabetes, and a second variant, near CCNL1, with no obvious link to adult traits2. In an expanded genome-wide association meta-analysis and follow-up study (up to 69,308 individuals of European descent from 43 studies), we have now extended the number of genome-wide significant loci to seven, accounting for a similar proportion of variance to maternal smoking. Five of the loci are known to be associated with other phenotypes: ADCY5 and CDKAL1 with type 2 diabetes; ADRB1 with adult blood pressure; and HMGA2 and LCORL with adult height. Our findings highlight genetic links between fetal growth and postnatal growth and metabolism. PMID:23202124

  14. Clinical Setting and Management Approach Matters: Metabolic Testing Rates in Antipsychotic-Treated Youth and Adults

    PubMed Central

    Nicol, Ginger; Campagna, Elizabeth J; Garfield, Lauren D; Newcomer, John W; Parks, Joe; Morrato, Elaine

    2015-01-01

    Background Guidelines recommend increased metabolic monitoring in antipsychotic-treated patients. State and federal agencies are striving to address under-screening. Methods Rates of glucose and lipid testing among antipsychotic-treated youth and adults in Missouri Medicaid (N=9,473) in Community Mental Health Centers (CMHCs), with and without case management, versus other care settings were evaluated. Multivariable logistic regressions determined which characteristics were independently associated with metabolic testing. Results Rates of glucose and lipid testing were 37.0% and 17.3% in youth and 68.7% and 34.9% in adults, respectively. Adjusted odds of glucose and lipid testing were higher in patients receiving care in a CMHC with case management [youth: AOR=1.68 (95% CI=1.37-2.04), 2.40(1.91-3.02); adults: 1.43(1.18-1.74), 1.97(1.64-2.36)], or without [youth: 1.89(1.61-2.22), 2.35(1.94-2.85); adults: 1.44(1.22-1.70), 1.48(1.27-1.74)] versus other settings. Conclusions Within Missouri Medicaid, receiving care at a CMHC was associated with higher rates of metabolic testing, possibly reflecting state efforts to promote health homes in these settings. PMID:26325456

  15. Adult human metapneumonovirus (hMPV) pneumonia mimicking Legionnaire's disease.

    PubMed

    Cunha, Burke A; Irshad, Nadia; Connolly, James J

    2016-01-01

    In adults hospitalized with viral pneumonias the main differential diagnostic consideration is influenza pneumonia. The respiratory viruses causing viral influenza like illnesses (ILIs), e.g., RSV may closely resemble influenza. Rarely, extrapulmonary findings of some ILIs may resemble Legionnaire's disease (LD), e.g., adenovirus, human parainfluenza virus (HPIV-3). We present a most unusual case of human metapneumonovirus pneumonia (hMPV) with some characteristic extrapulmonary findings characteristic of LD, e.g., relative bradycardia, as well as mildly elevated serum transaminases and hyphosphatemia. We believe this is the first reported case of hMPV pneumonia in a hospitalized adult that had some features of LD.

  16. Adult human metapneumonovirus (hMPV) pneumonia mimicking Legionnaire's disease.

    PubMed

    Cunha, Burke A; Irshad, Nadia; Connolly, James J

    2016-01-01

    In adults hospitalized with viral pneumonias the main differential diagnostic consideration is influenza pneumonia. The respiratory viruses causing viral influenza like illnesses (ILIs), e.g., RSV may closely resemble influenza. Rarely, extrapulmonary findings of some ILIs may resemble Legionnaire's disease (LD), e.g., adenovirus, human parainfluenza virus (HPIV-3). We present a most unusual case of human metapneumonovirus pneumonia (hMPV) with some characteristic extrapulmonary findings characteristic of LD, e.g., relative bradycardia, as well as mildly elevated serum transaminases and hyphosphatemia. We believe this is the first reported case of hMPV pneumonia in a hospitalized adult that had some features of LD. PMID:26988110

  17. [Pathological and metabolic bone diseases: Clinical importance for fracture treatment].

    PubMed

    Oheim, R

    2015-12-01

    Pathological and metabolic bone diseases are common and relevant occurrences in orthopedics and trauma surgery; however, fractures are often treated as being the illness itself and not seen as the symptom of an underlying bone disease. This is why further diagnostics and systemic treatment options are often insufficiently considered in the routine treatment of fractures. This review focuses on osteoporosis, osteopetrosis, hypophosphatasia and Paget's disease of bone.In patients with osteoporotic vertebral or proximal femur fractures, pharmaceutical treatment to prevent subsequent fractures is an integral part of fracture therapy together with surgical treatment. Osteopetrosis is caused by compromised osteoclastic bone resorption; therefore, even in the face of an elevated bone mass, vitamin D3 supplementation is crucial to avoid clinically relevant hypocalcemia. Unspecific symptoms of the musculoskeletal system, especially together with stress fractures, are typically found in patients suffering from hypophosphatasia. In these patients measurement of alkaline phosphatase shows reduced enzyme activity. Elevated levels of alkaline phosphatase are found in Paget's disease of bone where bisphosphonates are still the treatment of choice.

  18. Can We Prevent Obesity-Related Metabolic Diseases by Dietary Modulation of the Gut Microbiota?

    PubMed

    Brahe, Lena K; Astrup, Arne; Larsen, Lesli H

    2016-01-01

    Obesity increases the risk of type 2 diabetes, cardiovascular diseases, and certain cancers, which are among the leading causes of death worldwide. Obesity and obesity-related metabolic diseases are characterized by specific alterations in the human gut microbiota. Experimental studies with gut microbiota transplantations in mice and in humans indicate that a specific gut microbiota composition can be the cause and not just the consequence of the obese state and metabolic disease, which suggests a potential for gut microbiota modulation in prevention and treatment of obesity-related metabolic diseases. In addition, dietary intervention studies have suggested that modulation of the gut microbiota can improve metabolic risk markers in humans, but a causal role of the gut microbiota in such studies has not yet been established. Here, we review and discuss the role of the gut microbiota in obesity-related metabolic diseases and the potential of dietary modulation of the gut microbiota in metabolic disease prevention and treatment. PMID:26773017

  19. Can We Prevent Obesity-Related Metabolic Diseases by Dietary Modulation of the Gut Microbiota?

    PubMed

    Brahe, Lena K; Astrup, Arne; Larsen, Lesli H

    2016-01-01

    Obesity increases the risk of type 2 diabetes, cardiovascular diseases, and certain cancers, which are among the leading causes of death worldwide. Obesity and obesity-related metabolic diseases are characterized by specific alterations in the human gut microbiota. Experimental studies with gut microbiota transplantations in mice and in humans indicate that a specific gut microbiota composition can be the cause and not just the consequence of the obese state and metabolic disease, which suggests a potential for gut microbiota modulation in prevention and treatment of obesity-related metabolic diseases. In addition, dietary intervention studies have suggested that modulation of the gut microbiota can improve metabolic risk markers in humans, but a causal role of the gut microbiota in such studies has not yet been established. Here, we review and discuss the role of the gut microbiota in obesity-related metabolic diseases and the potential of dietary modulation of the gut microbiota in metabolic disease prevention and treatment.

  20. Impaired homocysteine metabolism in patients with alcoholic liver disease in Taiwan.

    PubMed

    Chien, Yi-Wen; Chen, Ya-Ling; Peng, Hsiang-Chi; Hu, Jui-Ting; Yang, Sien-Sing; Yang, Suh-Ching

    2016-08-01

    ​Impaired homocysteine metabolism plays an important role in alcoholic liver disease (ALD); however, there are limited data about its relationship with the risk and severity of patients with ALD in Taiwan. To understand plasma homocysteine and related vitamin concentrations in patients with ALD in Taiwan, we recruited 50 male patients with ALD from Cathay General Hospital, with 49 age-and gender-matched healthy adults as the control group. The Institutional Review Board for Human Studies approved the study, and informed consent was obtained from all patients prior to blood collection. Significantly higher plasma homocysteine concentrations but lower folate concentrations were obtained from patients with ALD. In addition, patients with ALD showed a significant lower erythrocyte reduced glutathione (GSH)/oxidized glutathione (GSSG) ratio but higher plasma thiobarbituric acid-reactive substance (TBARS) concentration, which indicated that oxidative stress was occurring in patients with ALD. A negative correlation between plasma folate and homocysteine was observed in all subjects. There was also a negative correlation between plasma homocysteine and the erythrocyte GSH/GSSG ratio which indicated impaired homocysteine metabolism may have disrupted the antioxidative status. In addition, patients in Child-Pugh Class B and C showed higher plasma vitamin B12 concentrations than did patients without cirrhosis and patients in Child-Pugh Class A. These findings show that impaired homocysteine metabolism was observed in patients with ALD in Taiwan. In addition, the plasma vitamin B12 concentration may reflect the degree of liver injury. PMID:27565754

  1. What is Metabolic Syndrome?

    MedlinePlus

    ... becoming more common due to a rise in obesity rates among adults. In the future, metabolic syndrome may overtake smoking as the leading risk factor for heart disease. It is possible to prevent or delay ...

  2. Understanding the Causes and Implications of Endothelial Metabolic Variation in Cardiovascular Disease through Genome-Scale Metabolic Modeling

    PubMed Central

    McGarrity, Sarah; Halldórsson, Haraldur; Palsson, Sirus; Johansson, Pär I.; Rolfsson, Óttar

    2016-01-01

    High-throughput biochemical profiling has led to a requirement for advanced data interpretation techniques capable of integrating the analysis of gene, protein, and metabolic profiles to shed light on genotype–phenotype relationships. Herein, we consider the current state of knowledge of endothelial cell (EC) metabolism and its connections to cardiovascular disease (CVD) and explore the use of genome-scale metabolic models (GEMs) for integrating metabolic and genomic data. GEMs combine gene expression and metabolic data acting as frameworks for their analysis and, ultimately, afford mechanistic understanding of how genetic variation impacts metabolism. We demonstrate how GEMs can be used to investigate CVD-related genetic variation, drug resistance mechanisms, and novel metabolic pathways in ECs. The application of GEMs in personalized medicine is also highlighted. Particularly, we focus on the potential of GEMs to identify metabolic biomarkers of endothelial dysfunction and to discover methods of stratifying treatments for CVDs based on individual genetic markers. Recent advances in systems biology methodology, and how these methodologies can be applied to understand EC metabolism in both health and disease, are thus highlighted. PMID:27148541

  3. Microvesicles and exosomes: new players in metabolic and cardiovascular disease.

    PubMed

    Lawson, Charlotte; Vicencio, Jose M; Yellon, Derek M; Davidson, Sean M

    2016-02-01

    The past decade has witnessed an exponential increase in the number of publications referring to extracellular vesicles (EVs). For many years considered to be extracellular debris, EVs are now seen as novel mediators of endocrine signalling via cell-to-cell communication. With the capability of transferring proteins and nucleic acids from one cell to another, they have become an attractive focus of research for different pathological settings and are now regarded as both mediators and biomarkers of disease including cardio-metabolic disease. They also offer therapeutic potential as signalling agents capable of targeting tissues or cells with specific peptides or miRNAs. In this review, we focus on the role that microvesicles (MVs) and exosomes, the two most studied classes of EV, have in diabetes, cardiovascular disease, endothelial dysfunction, coagulopathies, and polycystic ovary syndrome. We also provide an overview of current developments in MV/exosome isolation techniques from plasma and other fluids, comparing different available commercial and non-commercial methods. We describe different techniques for their optical/biochemical characterization and quantitation. We also review the signalling pathways that exosomes and MVs activate in target cells and provide some insight into their use as biomarkers or potential therapeutic agents. In summary, we give an updated focus on the role that these exciting novel nanoparticles offer for the endocrine community.

  4. Does metabolic failure at the synapse cause Alzheimer's disease?

    PubMed

    Engel, Peter A

    2014-12-01

    Alzheimer's disease (AD) a neurodegenerative disorder of widely distributed cortical networks evolves over years while A beta (Aβ) oligomer neurotoxicity occurs within seconds to minutes. This disparity combined with disappointing outcomes of anti-amyloid clinical trials challenges the centrality of Aβ as principal mediator of neurodegeneration. Reconsideration of late life AD as the end-product of intermittent regional failure of the neuronal support system to meet the needs of vulnerable brain areas offers an alternative point of view. This model introduces four ideas: (1) That Aβ is a synaptic signaling peptide that becomes toxic in circumstances of metabolic stress. (2) That intense synaptic energy and maintenance requirements of cortical hubs may exceed resources during peak demand initiating a neurotoxic cascade in these selectively vulnerable regions. (3) That axonal transport to and from neuron soma cannot account fully for high mitochondrial densities and other requirements of distant terminal axons. (4) That neurons as specialists in information management, delegate generic support functions to astrocytes and other cell types. Astrocytes use intercellular transport by exosomes and tunneling nanotubes (TNTs) to deliver mitochondria, substrates and protein reprocessing services to axonal sites distant from neuronal soma. This viewpoint implicates the brain's support system and its disruption by various age and disease-related insults as significant mediators of neurodegenerative disease. A better understanding of this system should broaden concepts of neurodegeneration and facilitate development of effective treatments.

  5. Role of NADPH Oxidase in Metabolic Disease-Related Renal Injury: An Update

    PubMed Central

    Su, Hua

    2016-01-01

    Metabolic syndrome has been linked to an increased risk of chronic kidney disease. The underlying pathogenesis of metabolic disease-related renal injury remains obscure. Accumulating evidence has shown that NADPH oxidase is a major source of intrarenal oxidative stress and is upregulated by metabolic factors leading to overproduction of ROS in podocytes, endothelial cells, and mesangial cells in glomeruli, which is closely associated with the initiation and progression of glomerular diseases. This review focuses on the role of NADPH oxidase-induced oxidative stress in the pathogenesis of metabolic disease-related renal injury. Understanding of the mechanism may help find potential therapeutic strategies.

  6. Role of NADPH Oxidase in Metabolic Disease-Related Renal Injury: An Update.

    PubMed

    Wan, Cheng; Su, Hua; Zhang, Chun

    2016-01-01

    Metabolic syndrome has been linked to an increased risk of chronic kidney disease. The underlying pathogenesis of metabolic disease-related renal injury remains obscure. Accumulating evidence has shown that NADPH oxidase is a major source of intrarenal oxidative stress and is upregulated by metabolic factors leading to overproduction of ROS in podocytes, endothelial cells, and mesangial cells in glomeruli, which is closely associated with the initiation and progression of glomerular diseases. This review focuses on the role of NADPH oxidase-induced oxidative stress in the pathogenesis of metabolic disease-related renal injury. Understanding of the mechanism may help find potential therapeutic strategies. PMID:27597884

  7. Role of NADPH Oxidase in Metabolic Disease-Related Renal Injury: An Update

    PubMed Central

    Su, Hua

    2016-01-01

    Metabolic syndrome has been linked to an increased risk of chronic kidney disease. The underlying pathogenesis of metabolic disease-related renal injury remains obscure. Accumulating evidence has shown that NADPH oxidase is a major source of intrarenal oxidative stress and is upregulated by metabolic factors leading to overproduction of ROS in podocytes, endothelial cells, and mesangial cells in glomeruli, which is closely associated with the initiation and progression of glomerular diseases. This review focuses on the role of NADPH oxidase-induced oxidative stress in the pathogenesis of metabolic disease-related renal injury. Understanding of the mechanism may help find potential therapeutic strategies. PMID:27597884

  8. Alterations in metabolic properties in fibroblasts in Alzheimer disease.

    PubMed

    Sorbi, S; Piacentini, S; Latorraca, S; Piersanti, P; Amaducci, L

    1995-01-01

    Alzheimer disease (AD) leads to alterations in several biochemical properties in cultured skin fibroblasts. Because abnormal glucose metabolism has been reported in both in vivo and in vitro studies of the brain, we examined glucose and glutamine oxidation and lactate production in cultured skin fibroblasts from nine patients with familial AD, 19 with sporadic AD, and 20 age-matched controls. The production of CO2 from glucose and glutamine was significantly lower in both groups of Alzheimer fibroblasts compared to controls after 10 min or 1, 2, and 4 h of incubation. The reduction in CO2 production was most evident after 1 h of incubation with either (U-14C)-glucose or (U-14C)-glutamine. Lactate concentration was comparable in all groups at any time of incubation. These findings suggest that processes that require mitochondrial function as glucose or glutamine oxidation are altered in AD and provide evidence that complex metabolic differences are expressed in cultured nonneuronal cells from Alzheimer patients. PMID:7662326

  9. Evidence of altered phosphatidylcholine metabolism in Alzheimer's disease.

    PubMed

    Whiley, Luke; Sen, Arundhuti; Heaton, James; Proitsi, Petroula; García-Gómez, Diego; Leung, Rufina; Smith, Norman; Thambisetty, Madhav; Kloszewska, Iwona; Mecocci, Patrizia; Soininen, Hilkka; Tsolaki, Magda; Vellas, Bruno; Lovestone, Simon; Legido-Quigley, Cristina

    2014-02-01

    Abberant lipid metabolism is implicated in Alzheimer's disease (AD) pathophysiology, but the connections between AD and lipid metabolic pathways are not fully understood. To investigate plasma lipids in AD, a multiplatform screen (n = 35 by liquid chromatography-mass spectrometry and n = 35 by nuclear magnetic resonance) was developed, which enabled the comprehensive analysis of plasma from 3 groups (individuals with AD, individuals with mild cognitive impairment (MCI), and age-matched controls). This screen identified 3 phosphatidylcholine (PC) molecules that were significantly diminished in AD cases. In a subsequent validation study (n = 141), PC variation in a bigger sample set was investigated, and the same 3 PCs were found to be significantly lower in AD patients: PC 16:0/20:5 (p < 0.001), 16:0/22:6 (p < 0.05), and 18:0/22:6 (p < 0.01). A receiver operating characteristic (ROC) analysis of the PCs, combined with apolipoprotein E (ApoE) data, produced an area under the curve predictive value of 0.828. Confirmatory investigations into the background biochemistry indiciated no significant change in plasma levels of 3 additional PCs of similar structure, total choline containing compounds or total plasma omega fatty acids, adding to the evidence that specific PCs play a role in AD pathology. PMID:24041970

  10. Metabolic Cost of Daily Activities and Effect of Mobility Impairment in Older Adults

    PubMed Central

    Knaggs, Jeffrey D; Larkin, Kelly A; Manini, Todd M

    2013-01-01

    OBJECTIVES There is a shortage of information on metabolic costs of daily physical activities in older adults and the effect of having mobility impairments. The primary purpose of this study was to evaluate metabolic equivalent (MET) values on common daily tasks in men and women aged > 70 years compared to normative criteria. A secondary purpose was to determine the effect of having mobility impairments. DESIGN Cross-sectional observational study. SETTING University based research clinic PARTICIPANTS Forty-five participants aged 70 to 90 years of age (mean: 76.3 ± 5.1) volunteered to complete 17 daily activities, each lasting 10 minutes. MEASUREMENTS Oxygen consumption (VO2 = ml•kg−1•min−1) was measured through a mask by a portable gas analyzer and MET values were calculated as measured VO2/3.5 ml•kg−1•min−1. Values were compared to both normative values and between participants with and without mobility impairments. RESULTS Compared to the established normative criteria, measured METs were different in 14 of 17 tasks performed. Compared to measured METs, normative values underestimated walking leisurely (0.87 ± 0.12 METs) walking briskly (0.87 ± 0.12 METs ), and bed making (1.07 ± 0.10 METs ), but overestimated gardening (1.46 ± 0.12 METs) and climbing stairs (0.73 ± 0.18). Participants with impairments had significantly lower METs while gardening, vacuuming/sweeping, stair climbing, and walking briskly. However, when METs were adjusted for performance speed the metabolic costs were 16–27% higher for those with mobility impairments. CONCLUSION Compared to normative values, metabolic costs of daily activities are substantially different in older adults and having mobility impairments increases this metabolic cost. These results may have implications for practitioners to appropriately prescribe daily physical activities for healthy and mobility impaired older adults. PMID:22091979

  11. Chronic kidney disease in an adult with propionic acidemia.

    PubMed

    Vernon, H J; Bagnasco, S; Hamosh, A; Sperati, C J

    2014-01-01

    We report an adult male with classic propionic acidemia (PA) who developed chronic kidney disease in the third decade of his life. This diagnosis was recognized by an increasing serum creatinine and confirmed by reduced glomerular filtration on a (99m)Tc-diethylenetriamine pentaacetate (DTPA) scan. Histopathology of the kidney showed moderate glomerulo- and tubulointerstitial fibrosis with very segmental mesangial IgA deposits. This is the second reported case of kidney disease in an individual with propionic acidemia possibly indicating that chronic kidney disease may be a late-stage complication of propionic acidemia. Additionally, this is the first description of the histopathology of kidney disease in an individual with propionic acidemia. As more cases emerge, the clinical course and spectrum of renal pathology in this disorder will be better defined.

  12. Sirtuins: Novel targets for metabolic disease in drug development

    SciTech Connect

    Jiang Weijian

    2008-08-29

    Calorie restriction extends lifespan and produces a metabolic profile desirable for treating diseases such as type 2 diabetes. SIRT1, an NAD{sup +}-dependent deacetylase, is a principal modulator of pathways downstream of calorie restriction that produces beneficial effects on glucose homeostasis and insulin sensitivity. Activation of SIRT1 leads to enhanced activity of multiple proteins, including peroxisome proliferator-activated receptor coactivator-1{alpha} (PGC-1{alpha}) and FOXO which helps to mediate some of the in vitro and in vivo effects of sirtuins. Resveratrol, a polyphenolic SIRT1 activator, mimics the effects of calorie restriction in lower organisms and in mice fed a high-fat diet ameliorates insulin resistance. In this review, we summarize recent research advances in unveiling the molecular mechanisms that underpin sirtuin as therapeutic candidates and discuss the possibility of using resveratrol as potential drug for treatment of diabetes.

  13. Low-Dose Cadmium Causes Metabolic and Genetic Dysregulation Associated With Fatty Liver Disease in Mice

    PubMed Central

    Go, Young-Mi; Sutliff, Roy L.; Chandler, Joshua D.; Khalidur, Rahman; Kang, Bum-Yong; Anania, Frank A.; Orr, Michael; Hao, Li; Fowler, Bruce A.; Jones, Dean P.

    2015-01-01

    Cadmium (Cd) is present in food at low levels and accumulates in humans throughout life because it is not effectively excreted. Cd from smoking or occupational exposure shows adverse effects on health, but the mechanistic effect of Cd at low dietary intake levels is poorly studied. Epidemiology studies found that nonalcoholic fatty liver disease (NAFLD), common in U.S. adults, is associated with Cd burden. In cell studies, we found that environmental low-dose Cd oxidized proteins and stimulated inflammatory signaling. However, little is known about low-dose Cd effects on liver function and associated metabolic pathways in vivo. We investigated effects of low-level Cd exposure on liver gene transcripts, metabolites, and associated metabolic pathways and function after challenging mice with Cd (10 mg/l) by drinking water. Results showed liver Cd in treated mice was similar to adult humans without occupational or smoking exposures and 10-fold higher than control mouse values. Pathway analysis of significantly altered liver genes and metabolites mapped to functional pathways of lipid metabolism, cell death and mitochondrial oxidative phosphorylation. These are well-recognized pathways associated with NAFLD. Cd–treated mice had higher liver enzymes in plasma and a trend toward fat accumulation in liver. To verify low-dose Cd-induced stimulation of cell death pathways, phosphorylation of c-Jun N-terminal kinase (JNK) was examined in cultured hepatic cells. Consistent with mouse liver data, low-dose Cd stimulated JNK activation. Together, the results show that low-dose Cd exposure causes liver function changes consistent with a role in NAFLD and possibly also nonalcoholic steatohepatitis. PMID:26187450

  14. Low-Dose Cadmium Causes Metabolic and Genetic Dysregulation Associated With Fatty Liver Disease in Mice.

    PubMed

    Go, Young-Mi; Sutliff, Roy L; Chandler, Joshua D; Khalidur, Rahman; Kang, Bum-Yong; Anania, Frank A; Orr, Michael; Hao, Li; Fowler, Bruce A; Jones, Dean P

    2015-10-01

    Cadmium (Cd) is present in food at low levels and accumulates in humans throughout life because it is not effectively excreted. Cd from smoking or occupational exposure shows adverse effects on health, but the mechanistic effect of Cd at low dietary intake levels is poorly studied. Epidemiology studies found that nonalcoholic fatty liver disease (NAFLD), common in U.S. adults, is associated with Cd burden. In cell studies, we found that environmental low-dose Cd oxidized proteins and stimulated inflammatory signaling. However, little is known about low-dose Cd effects on liver function and associated metabolic pathways in vivo. We investigated effects of low-level Cd exposure on liver gene transcripts, metabolites, and associated metabolic pathways and function after challenging mice with Cd (10 mg/l) by drinking water. Results showed liver Cd in treated mice was similar to adult humans without occupational or smoking exposures and 10-fold higher than control mouse values. Pathway analysis of significantly altered liver genes and metabolites mapped to functional pathways of lipid metabolism, cell death and mitochondrial oxidative phosphorylation. These are well-recognized pathways associated with NAFLD. Cd-treated mice had higher liver enzymes in plasma and a trend toward fat accumulation in liver. To verify low-dose Cd-induced stimulation of cell death pathways, phosphorylation of c-Jun N-terminal kinase (JNK) was examined in cultured hepatic cells. Consistent with mouse liver data, low-dose Cd stimulated JNK activation. Together, the results show that low-dose Cd exposure causes liver function changes consistent with a role in NAFLD and possibly also nonalcoholic steatohepatitis.

  15. The global burden of chronic respiratory disease in adults.

    PubMed

    Burney, P; Jarvis, D; Perez-Padilla, R

    2015-01-01

    With an aging global population, chronic respiratory diseases are becoming a more prominent cause of death and disability. Age-standardised death rates from chronic obstructive pulmonary disease (COPD) are highest in low-income regions of the world, particularly South Asia and sub-Saharan Africa, although airflow obstruction is relatively uncommon in these areas. Airflow obstruction is, by contrast, more common in regions with a high prevalence of cigarette smoking. COPD mortality is much more closely related to the prevalence of a low forced vital capacity which is, in turn, associated with poverty. Mortality from asthma is less common than mortality from COPD, but it is also relatively more common in poorer areas, particularly Oceania, South and South-East Asia, the Middle East and Africa. Again this contrasts with the asthma prevalence among adults, which is highest in high-income regions. In high-income areas, mortality due to asthma, which is predominantly an adult problem, has fallen substantially in recent decades with the spread of new guidelines for treatment that emphasise the use of inhaled steroids to control the disease. Although mortality rates have been falling, the prevalence of atopy has been increasing between generations in Western Europe. Changes in the prevalence of wheeze among adults has been more varied and may have been influenced by the reduction in smoking and the increase in the use of inhaled steroids. PMID:25519785

  16. Triheptanoin improves brain energy metabolism in patients with Huntington disease

    PubMed Central

    Adanyeguh, Isaac Mawusi; Rinaldi, Daisy; Henry, Pierre-Gilles; Caillet, Samantha; Valabregue, Romain; Durr, Alexandra

    2015-01-01

    Objective: Based on our previous work in Huntington disease (HD) showing improved energy metabolism in muscle by providing substrates to the Krebs cycle, we wished to obtain a proof-of-concept of the therapeutic benefit of triheptanoin using a functional biomarker of brain energy metabolism validated in HD. Methods: We performed an open-label study using 31P brain magnetic resonance spectroscopy (MRS) to measure the levels of phosphocreatine (PCr) and inorganic phosphate (Pi) before (rest), during (activation), and after (recovery) a visual stimulus. We performed 31P brain MRS in 10 patients at an early stage of HD and 13 controls. Patients with HD were then treated for 1 month with triheptanoin after which they returned for follow-up including 31P brain MRS scan. Results: At baseline, we confirmed an increase in Pi/PCr ratio during brain activation in controls—reflecting increased adenosine triphosphate synthesis—followed by a return to baseline levels during recovery (p = 0.013). In patients with HD, we validated the existence of an abnormal brain energy profile as previously reported. After 1 month, this profile remained abnormal in patients with HD who did not receive treatment. Conversely, the MRS profile was improved in patients with HD treated with triheptanoin for 1 month with the restoration of an increased Pi/PCr ratio during visual stimulation (p = 0.005). Conclusion: This study suggests that triheptanoin is able to correct the bioenergetic profile in the brain of patients with HD at an early stage of the disease. Classification of evidence: This study provides Class III evidence that, for patients with HD, treatment with triheptanoin for 1 month restores an increased MRS Pi/PCr ratio during visual stimulation. PMID:25568297

  17. Resting metabolic connectivity in prodromal Alzheimer's disease. A European Alzheimer Disease Consortium (EADC) project.

    PubMed

    Morbelli, Silvia; Drzezga, Alex; Perneczky, Robert; Frisoni, Giovanni B; Caroli, Anna; van Berckel, Bart N M; Ossenkoppele, Rik; Guedj, Eric; Didic, Mira; Brugnolo, Andrea; Sambuceti, Gianmario; Pagani, Marco; Salmon, Eric; Nobili, Flavio

    2012-11-01

    We explored resting-state metabolic connectivity in prodromal Alzheimer's disease (pAD) patients and in healthy controls (CTR), through a voxel-wise interregional correlation analysis of 18F-fluorodeoxyglucose (FDG)-positron emission tomography (PET) by means of statistical parametric mapping. Baseline 18F-fluorodeoxyglucose-positron emission tomography of 36 patients with amnestic mild cognitive impairment who converted to Alzheimer's disease (AD) dementia after an average time of 2 years (pAD) and of 105 CTR were processed. The area of hypometabolism in pAD showed less metabolic connectivity in patients than in CTR (autocorrelation and correlation with large temporal and frontal areas, respectively). pAD patients showed limited correlation even in selected nonhypometabolic areas, including the hippocampi and the dorsolateral prefrontal cortex (DLFC). On the contrary, in CTR group correlation was highlighted between hippocampi and precuneus/posterior cingulate and frontal cortex, and between dorsolateral prefrontal cortex and caudate nuclei and parietal cortex. The reduced metabolic connections both in hypometabolic and nonhypometabolic areas in pAD patients suggest that metabolic disconnection (reflecting early diaschisis) may antedate remote hypometabolism (early sign of synaptic degeneration).

  18. ECHS1 mutations in Leigh disease: a new inborn error of metabolism affecting valine metabolism.

    PubMed

    Peters, Heidi; Buck, Nicole; Wanders, Ronald; Ruiter, Jos; Waterham, Hans; Koster, Janet; Yaplito-Lee, Joy; Ferdinandusse, Sacha; Pitt, James

    2014-11-01

    Two siblings with fatal Leigh disease had increased excretion of S-(2-carboxypropyl)cysteine and several other metabolites that are features of 3-hydroxyisobutyryl-CoA hydrolase (HIBCH) deficiency, a rare defect in the valine catabolic pathway associated with Leigh-like disease. However, this diagnosis was excluded by HIBCH sequencing and normal enzyme activity. In contrast to HIBCH deficiency, the excretion of 3-hydroxyisobutyryl-carnitine was normal in the children, suggesting deficiency of short-chain enoyl-CoA hydratase (ECHS1 gene). This mitochondrial enzyme is active in several metabolic pathways involving fatty acids and amino acids, including valine, and is immediately upstream of HIBCH in the valine pathway. Both children were compound heterozygous for a c.473C > A (p.A158D) missense mutation and a c.414+3G>C splicing mutation in ECHS1. ECHS1 activity was markedly decreased in cultured fibroblasts from both siblings, ECHS1 protein was undetectable by immunoblot analysis and transfection of patient cells with wild-type ECHS1 rescued ECHS1 activity. The highly reactive metabolites methacrylyl-CoA and acryloyl-CoA accumulate in deficiencies of both ECHS1 and HIBCH and are probably responsible for the brain pathology in both disorders. Deficiency of ECHS1 or HIBCH should be considered in children with Leigh disease. Urine metabolite testing can detect and distinguish between these two disorders.

  19. Neridronic acid for the treatment of bone metabolic diseases.

    PubMed

    Gatti, Davide; Viapiana, Ombretta; Idolazzi, Luca; Fracassi, Elena; Adami, Silvano

    2009-10-01

    Neridronic acid (6-amino-1-idroxyesilidene-1,1-bisphosphonate) is a nitrogen-containing bisphosphonate licensed in Italy for the treatment of osteogenesis imperfecta and Paget's disease of bone. The pharmacodynamic profile is similar to that of other nitrogen-containing bisphosphonates and is characterized by its high affinity for bone tissue particularly at sites undergoing a process of remodeling. In growing children affected by osteogenesis imperfect, neridronic acid rapidly increases bone mineral density as measured by dual X-ray absortiometry and this is associated with a significant decrease in fracture cumulative number. Similar results have been obtained also in newborns (< 12 month old) and in adult patients. In Paget's disease of bone, 200 mg intravenous neridronic acid is associated with a 65% rate of full remission and a biochemical response (decrease of > 75% of bone turnover markers) in 95% of the patients. Neridronic acid treatment has been reported to be effective also in other skeletal diseases such as osteoporosis, algodystrophy, hypercalcemia of malignancy and bone metastasis. Neridronic acid has been developed only for parenteral use, and it is the only one used as intramuscular injection. This avoids all the limitations of oral bisphosphonates and may be offered for a home treatment with simple nursing assistance. PMID:19761412

  20. Screening and Management of Depression for Adults With Chronic Diseases

    PubMed Central

    2013-01-01

    Background Depression is the leading cause of disability and the fourth leading contributor to the global burden of disease. In Canada, the 1-year prevalence of major depressive disorder was approximately 6% in Canadians 18 and older. A large prospective Canadian study reported an increased risk of developing depression in people with chronic diseases compared with those without such diseases. Objectives To systematically review the literature regarding the effectiveness of screening for depression and/or anxiety in adults with chronic diseases in the community setting. To conduct a non-systematic, post-hoc analysis to evaluate whether a screen-and-treat strategy for depression is associated with an improvement in chronic disease outcomes. Data Sources A literature search was performed on January 29, 2012, using OVID MEDLINE, OVID MEDLINE In-Process and Other Non-Indexed Citations, OVID EMBASE, OVID PsycINFO, EBSCO Cumulative Index to Nursing & Allied Health Literature (CINAHL), the Wiley Cochrane Library, and the Centre for Reviews and Dissemination database, for studies published from January 1, 2002 until January 29, 2012. Review Methods No citations were identified for the first objective. For the second, systematic reviews and randomized controlled trials that compared depression management for adults with chronic disease with usual care/placebo were included. Where possible, the results of randomized controlled trials were pooled using a random-effects model. Results Eight primary randomized controlled trials and 1 systematic review were included in the post-hoc analysis (objective 2)—1 in people with diabetes, 2 in people with heart failure, and 5 in people with coronary artery disease. Across all studies, there was no evidence that managing depression improved chronic disease outcomes. The quality of evidence (GRADE) ranged from low to moderate. Some of the study results (specifically in coronary artery disease populations) were suggestive of benefit, but

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

    PubMed Central

    Martin, Francois-Pierre; Ezri, Jessica; Cominetti, Ornella; Da Silva, Laeticia; Kussmann, Martin; Godin, Jean-Philippe; Nydegger, Andreas

    2016-01-01

    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. PMID:27529220

  2. Dicarbonyl proteome and genome damage in metabolic and vascular disease.

    PubMed

    Rabbani, Naila; Thornalley, Paul J

    2014-04-01

    Methylglyoxal is a potent protein-glycating agent. It is an arginine-directed glycating agent and often modifies functionally important sites in proteins. Glycation forms mainly MG-H1 [Nδ-(5-hydro-5-methyl-4-imidazolon-2-yl)ornithine] residues. MG-H1 content of proteins is quantified by stable isotopic dilution analysis-MS/MS and also by immunoblotting with specific monoclonal antibodies. Methylglyoxal-modified proteins undergo cellular proteolysis and release MG-H1 free adduct for excretion. MG-H1 residues have been found in proteins of animals, plants, bacteria, fungi and protoctista. MG-H1 is often the major advanced glycation end-product in proteins of tissues and body fluids, increasing in diabetes and associated vascular complications, renal failure, cirrhosis, Alzheimer's disease, arthritis, Parkinson's disease and aging. Proteins susceptible to methylglyoxal modification with related functional impairment are called the DCP (dicarbonyl proteome). The DCP includes albumin, haemoglobin, transcription factors, mitochondrial proteins, extracellular matrix proteins, lens crystallins and others. DCP component proteins are linked to mitochondrial dysfunction in diabetes and aging, oxidative stress, dyslipidaemia, cell detachment and anoikis and apoptosis. Methylglyoxal also modifies DNA where deoxyguanosine residues are modified to imidazopurinone MGdG {3-(2'-deoxyribosyl)-6,7-dihydro-6,7-dihydroxy-6/7-methylimidazo-[2,3-b]purine-9(8)one} isomers. MGdG was the major quantitative adduct detected in vivo. It was linked to frequency of DNA strand breaks and increased markedly during apoptosis induced by a cell-permeant glyoxalase I inhibitor. Glyoxalase I metabolizes >99% methylglyoxal and thereby protects the proteome and genome. Gene deletion of GLO1 is embryonically lethal and GLO1 silencing increases methylglyoxal concentration, MG-H1 and MGdG, premature aging and disease. Studies of methylglyoxal glycation have importance for human health, longevity and

  3. Dicarbonyl proteome and genome damage in metabolic and vascular disease.

    PubMed

    Rabbani, Naila; Thornalley, Paul J

    2014-04-01

    Methylglyoxal is a potent protein-glycating agent. It is an arginine-directed glycating agent and often modifies functionally important sites in proteins. Glycation forms mainly MG-H1 [Nδ-(5-hydro-5-methyl-4-imidazolon-2-yl)ornithine] residues. MG-H1 content of proteins is quantified by stable isotopic dilution analysis-MS/MS and also by immunoblotting with specific monoclonal antibodies. Methylglyoxal-modified proteins undergo cellular proteolysis and release MG-H1 free adduct for excretion. MG-H1 residues have been found in proteins of animals, plants, bacteria, fungi and protoctista. MG-H1 is often the major advanced glycation end-product in proteins of tissues and body fluids, increasing in diabetes and associated vascular complications, renal failure, cirrhosis, Alzheimer's disease, arthritis, Parkinson's disease and aging. Proteins susceptible to methylglyoxal modification with related functional impairment are called the DCP (dicarbonyl proteome). The DCP includes albumin, haemoglobin, transcription factors, mitochondrial proteins, extracellular matrix proteins, lens crystallins and others. DCP component proteins are linked to mitochondrial dysfunction in diabetes and aging, oxidative stress, dyslipidaemia, cell detachment and anoikis and apoptosis. Methylglyoxal also modifies DNA where deoxyguanosine residues are modified to imidazopurinone MGdG {3-(2'-deoxyribosyl)-6,7-dihydro-6,7-dihydroxy-6/7-methylimidazo-[2,3-b]purine-9(8)one} isomers. MGdG was the major quantitative adduct detected in vivo. It was linked to frequency of DNA strand breaks and increased markedly during apoptosis induced by a cell-permeant glyoxalase I inhibitor. Glyoxalase I metabolizes >99% methylglyoxal and thereby protects the proteome and genome. Gene deletion of GLO1 is embryonically lethal and GLO1 silencing increases methylglyoxal concentration, MG-H1 and MGdG, premature aging and disease. Studies of methylglyoxal glycation have importance for human health, longevity and

  4. Engineering Fat Cell Fate to Fight Obesity and Metabolic Diseases.

    PubMed

    Kajimura, Shingo

    2015-01-01

    All mammals harbor two types of adipose tissues that serve distinct physiological functions: white adipose tissue (WAT) and brown adipose tissue (BAT). WAT functions mainly in the storage of excess energy, while BAT specializes in dissipating energy in the form of heat and functions as a defense against hypothermia and obesity. Since adult humans possess significant amounts of active BAT depots and it's mass inversely correlates with adiposity, BAT plays an important role in human obesity and energy homeostasis.New evidence suggests two types of thermogenic adipocytes with distinct developmental and anatomical features: classical brown adipocytes and beige adipocytes. Classical brown adipocytes are located mainly in dedicated BAT depots of rodents and infants. Beige adipocytes, on the other hand, reside mainly in subcutaneous WAT where they arise postnatally in response to certain external cues, such as chronic cold exposure and long-term treatment with PPAR- agonists, a process often referred to as the "browning" of WAT. Importantly, adult human BAT appears to be mainly composed of beige-like adipocytes, making this cell type an attractive therapeutic target for obesity and obesity-related diseases, such as insulin resistance and type2 diabetes. I will review recent progress in the molecular control of brown and beige adipocyte development and discuss emerging questions.(Presented at the 1912th Meeting, December 21, 2015). PMID:26727580

  5. Engineering Fat Cell Fate to Fight Obesity and Metabolic Diseases.

    PubMed

    Kajimura, Shingo

    2015-01-01

    All mammals harbor two types of adipose tissues that serve distinct physiological functions: white adipose tissue (WAT) and brown adipose tissue (BAT). WAT functions mainly in the storage of excess energy, while BAT specializes in dissipating energy in the form of heat and functions as a defense against hypothermia and obesity. Since adult humans possess significant amounts of active BAT depots and it's mass inversely correlates with adiposity, BAT plays an important role in human obesity and energy homeostasis.New evidence suggests two types of thermogenic adipocytes with distinct developmental and anatomical features: classical brown adipocytes and beige adipocytes. Classical brown adipocytes are located mainly in dedicated BAT depots of rodents and infants. Beige adipocytes, on the other hand, reside mainly in subcutaneous WAT where they arise postnatally in response to certain external cues, such as chronic cold exposure and long-term treatment with PPAR- agonists, a process often referred to as the "browning" of WAT. Importantly, adult human BAT appears to be mainly composed of beige-like adipocytes, making this cell type an attractive therapeutic target for obesity and obesity-related diseases, such as insulin resistance and type2 diabetes. I will review recent progress in the molecular control of brown and beige adipocyte development and discuss emerging questions.(Presented at the 1912th Meeting, December 21, 2015).

  6. Brain glucose metabolism in adults with ataxia-telangiectasia and their asymptomatic relatives.

    PubMed

    Volkow, Nora D; Tomasi, Dardo; Wang, Gene-Jack; Studentsova, Yana; Margus, Brad; Crawford, Thomas O

    2014-06-01

    Ataxia-telangiectasia is a recessive genetic disorder (ATM is the mutated gene) of childhood with severe motor impairments and whereas homozygotes manifest the disorder, heterozygotes are asymptomatic. Structural brain imaging and post-mortem studies in individuals with ataxia-telangiectasia have reported cerebellar atrophy; but abnormalities of motor control characteristic of extrapyramidal dysfunction suggest impairment of broader motor networks. Here, we investigated possible dysfunction in other brain areas in individuals with ataxia-telangiectasia and tested for brain changes in asymptomatic relatives to assess if heterozygocity affects brain function. We used positron emission tomography and (18)F-fluorodeoxyglucose to measure brain glucose metabolism (quantified as µmol/100 g/min), which serves as a marker of brain function, in 10 adults with ataxia-telangiectasia, 19 non-affected adult relatives (12 siblings, seven parents) and 29 age-matched healthy controls. Statistical parametric mapping and region of interest analyses were used to compare individuals with ataxia-telangiectasia, asymptomatic relatives, and unrelated controls. We found that participants with ataxia-telangiectasia had lower metabolism in cerebellar hemispheres (14%, P < 0.001), anterior vermis (40%, P < 0.001) and fusiform gyrus (20%, P < 0.001) compared with controls or siblings, and lower metabolism in hippocampus (12%, P = 0.05) compared with controls, and showed significant intersubject variability (decreases in vermis ranged from 18% to 60%). Participants with ataxia-telangiectasia also had higher metabolism in globus pallidus (16%, P = 0.05), which correlated negatively with motor performance. Asymptomatic relatives had lower metabolism in anterior vermis (12%; P = 0.01) and hippocampus (19%; P = 0.002) than controls. Our results indicate that, in addition to the expected decrease in cerebellar metabolism, participants with ataxia-telangiectasia had widespread changes in metabolic

  7. Brain glucose metabolism in adults with ataxia-telangiectasia and their asymptomatic relatives.

    PubMed

    Volkow, Nora D; Tomasi, Dardo; Wang, Gene-Jack; Studentsova, Yana; Margus, Brad; Crawford, Thomas O

    2014-06-01

    Ataxia-telangiectasia is a recessive genetic disorder (ATM is the mutated gene) of childhood with severe motor impairments and whereas homozygotes manifest the disorder, heterozygotes are asymptomatic. Structural brain imaging and post-mortem studies in individuals with ataxia-telangiectasia have reported cerebellar atrophy; but abnormalities of motor control characteristic of extrapyramidal dysfunction suggest impairment of broader motor networks. Here, we investigated possible dysfunction in other brain areas in individuals with ataxia-telangiectasia and tested for brain changes in asymptomatic relatives to assess if heterozygocity affects brain function. We used positron emission tomography and (18)F-fluorodeoxyglucose to measure brain glucose metabolism (quantified as µmol/100 g/min), which serves as a marker of brain function, in 10 adults with ataxia-telangiectasia, 19 non-affected adult relatives (12 siblings, seven parents) and 29 age-matched healthy controls. Statistical parametric mapping and region of interest analyses were used to compare individuals with ataxia-telangiectasia, asymptomatic relatives, and unrelated controls. We found that participants with ataxia-telangiectasia had lower metabolism in cerebellar hemispheres (14%, P < 0.001), anterior vermis (40%, P < 0.001) and fusiform gyrus (20%, P < 0.001) compared with controls or siblings, and lower metabolism in hippocampus (12%, P = 0.05) compared with controls, and showed significant intersubject variability (decreases in vermis ranged from 18% to 60%). Participants with ataxia-telangiectasia also had higher metabolism in globus pallidus (16%, P = 0.05), which correlated negatively with motor performance. Asymptomatic relatives had lower metabolism in anterior vermis (12%; P = 0.01) and hippocampus (19%; P = 0.002) than controls. Our results indicate that, in addition to the expected decrease in cerebellar metabolism, participants with ataxia-telangiectasia had widespread changes in metabolic

  8. [Pediatric cardiology and congenital heart disease: from fetus to adult].

    PubMed

    Subirana, M Teresa; Oliver, José M; Sáez, José M; Zunzunegui, José L

    2012-01-01

    This article contains a review of some of the most important publications on congenital heart disease and pediatric cardiology that appeared in 2010 and up until September 2011. Of particular interest were studies on demographic changes reported in this patient population and on the need to manage the patients' transition from the pediatric to the adult cardiology department. This transition has given rise to the appearance of new areas of interest: for example, pregnancy in women with congenital heart disease, and the effect of genetic factors on the etiology and transmission of particular anomalies. In addition, this review considers some publications on fetal cardiology from the perspective of early diagnosis and, if possible, treatment. There follows a discussion on new contributions to Eisenmenger's syndrome and arrhythmias, as well as on imaging techniques, interventional catheterization and heart transplantation. Finally, there is an overview of the new version of clinical practice guidelines on the management of adult patients with congenital heart disease and of recently published guidelines on pregnancy in women with heart disease, both produced by the European Society of Cardiology.

  9. Cytoskeletal disease: a role in the etiology of adult periodontitis.

    PubMed

    Binderman, I; Gadban, N; Yaffe, A

    2014-01-01

    All cells and organisms across the evolutionary spectrum, from the most primitive to the most complex, are mechanosensitive. As the cytoskeleton is a key in controlling the normal basal prestress of cells and therefore is involved in virtually all physiological cellular processes, abnormalities in this essential cellular characteristic may result in diseases. Indeed, many diseases have now been associated with abnormalities in cytoskeletal and nucleoskeletal proteins. We propose that adult periodontitis is, at least in part, such a cytoskeletal disease. It is well established that adult periodontitis starts by bacterial invasion at the interface between the tooth surface and marginal gingiva that induces a local inflammatory response. The inflammatory cells release metalloproteinases which degrade gingival collagenous fibrous tissue and loss of local tissue integrity that reduces the normal prestressed cell-extracellular matrix network. This is a major signaling trigger that induces a local and rapid release of ATP, which then activates P2X receptors and stimulates a calcium influx, further activating osteoclastic resorption of the alveolar bone. As periodontitis is a chronic disease, it seems reasonable to suggest that agents that maintain cytoskeletal tensegrity, for example, inhibitors of ATP receptors, may diminish the bone loss and may have a role in future periodontal therapy. PMID:23679579

  10. The Risk of Metabolic Syndrome among Institutionalized Adults with Intellectual Disabilities

    ERIC Educational Resources Information Center

    Hsu, Shang-Wei; Yen, Chia-Feng; Hung, Wen-Jui; Lin, Lam-Ping; Wu, Chia-Ling; Lin, Jin-Ding

    2012-01-01

    People with metabolic syndrome (MS) are at increased risk of coronary heart disease and other health problems, such as diabetes and stroke. However, there is little previous information on the prevalence and determinants of MS among people with intellectual disabilities (IDs). The present study aimed to examine the prevalence of MS risk factors…

  11. Posttraumatic Stress Disorder, Cardiovascular and Metabolic Disease: A Review of the Evidence

    PubMed Central

    Dedert, Eric A.; Calhoun, Patrick S.; Watkins, Lana L.; Sherwood, Andrew; Beckham, Jean C.

    2011-01-01

    Background Posttraumatic stress disorder (PTSD) is a significant risk factor for cardiovascular and metabolic disease. Purpose The purpose of the current review is to evaluate the evidence suggesting that PTSD increases cardiovascular and metabolic risk factors, and to identify possible biomarkers and psychosocial characteristics and behavioral variables that are associated with these outcomes. Methods A systematic literature search in the period of 2002–2009 for PTSD, cardiovascular disease, and metabolic disease was conducted. Results The literature search yielded 78 studies on PTSD and cardiovascular/metabolic disease and biomarkers. Conclusions Although the available literature suggests an association of PTSD with cardiovascular disease and biomarkers, further research must consider potential confounds, incorporate longitudinal designs, and conduct careful PTSD assessments in diverse samples to address gaps in the research literature. Research on metabolic disease and biomarkers suggests an association with PTSD, but has not progressed as far as the cardiovascular research. PMID:20174903

  12. Exploring the metabolic syndrome: Nonalcoholic fatty pancreas disease.

    PubMed

    Catanzaro, Roberto; Cuffari, Biagio; Italia, Angelo; Marotta, Francesco

    2016-09-14

    After the first description of fatty pancreas in 1933, the effects of pancreatic steatosis have been poorly investigated, compared with that of the liver. However, the interest of research is increasing. Fat accumulation, associated with obesity and the metabolic syndrome (MetS), has been defined as "fatty infiltration" or "nonalcoholic fatty pancreas disease" (NAFPD). The term "fatty replacement" describes a distinct phenomenon characterized by death of acinar cells and replacement by adipose tissue. Risk factors for developing NAFPD include obesity, increasing age, male sex, hypertension, dyslipidemia, alcohol and hyperferritinemia. Increasing evidence support the role of pancreatic fat in the development of type 2 diabetes mellitus, MetS, atherosclerosis, severe acute pancreatitis and even pancreatic cancer. Evidence exists that fatty pancreas could be used as the initial indicator of "ectopic fat deposition", which is a key element of nonalcoholic fatty liver disease and/or MetS. Moreover, in patients with fatty pancreas, pancreaticoduodenectomy is associated with an increased risk of intraoperative blood loss and post-operative pancreatic fistula.

  13. Gender differences in glutathione metabolism in Alzheimer's disease.

    PubMed

    Liu, Honglei; Harrell, Lindy E; Shenvi, Swapna; Hagen, Tory; Liu, Rui-Ming

    2005-03-15

    The mechanism underlying Alzheimer's disease (AD), an age-related neurodegenerative disease, is still an area of significant controversy. Oxidative damage of macromolecules has been suggested to play an important role in the development of AD; however, the underlying mechanism is still unclear. In this study, we showed that the concentration of glutathione (GSH), the most abundant intracellular free thiol and an important antioxidant, was decreased in red blood cells from male AD patients compared with age- and gender-matched controls. However, there was no difference in blood GSH concentration between the female patients and female controls. The decrease in GSH content in red blood cells from male AD patients was associated with reduced activities of glutamate cysteine ligase and glutathione synthase, the two enzymes involved in de novo GSH synthesis, with no change in the amount of oxidized glutathione or the activity of glutathione reductase, suggesting that a decreased de novo GSH synthetic capacity is responsible for the decline in GSH content in AD. These results showed for the first time that GSH metabolism was regulated differently in male and female AD patients. PMID:15693022

  14. Enzymology of mammalian NAD metabolism in health and disease.

    PubMed

    Magni, Giulio; Orsomando, Giuseppe; Raffelli, Nadia; Ruggieri, Silverio

    2008-01-01

    Mounting evidence attests to the paramount importance of the non-redox NAD functions. Indeed, NAD homeostasis is related to the free radicals-mediated production of reactive oxygen species responsible for irreversible cellular damage in infectious disease, diabetes, inflammatory syndromes, neurodegeneration and cancer. Because the cellular redox status depends on both the absolute concentration of pyridine dinucleotides and their respective ratios of oxidized and reduced forms (i.e., NAD/NADH and NADP/NADPH), it is conceivable that an altered regulation of the synthesis and degradation of NAD impairs the cell redox state and likely contributes to the mechanisms underlying the pathogenesis of the above mentioned diseases. Taking into account the recent appearance in the literature of comprehensive reviews covering different aspects of the significance of NAD metabolism, with particular attention to the enzymes involved in NAD cleavage, this monograph includes the most recent results on NAD biosynthesis in mammals and humans. Due to recent findings on nicotinamide riboside as a nutrient, its inclusion under "niacins" is proposed. Here, the enzymes involved in the de novo and reutilization pathways are overviewed. PMID:18508649

  15. Exploring the metabolic syndrome: Nonalcoholic fatty pancreas disease.

    PubMed

    Catanzaro, Roberto; Cuffari, Biagio; Italia, Angelo; Marotta, Francesco

    2016-09-14

    After the first description of fatty pancreas in 1933, the effects of pancreatic steatosis have been poorly investigated, compared with that of the liver. However, the interest of research is increasing. Fat accumulation, associated with obesity and the metabolic syndrome (MetS), has been defined as "fatty infiltration" or "nonalcoholic fatty pancreas disease" (NAFPD). The term "fatty replacement" describes a distinct phenomenon characterized by death of acinar cells and replacement by adipose tissue. Risk factors for developing NAFPD include obesity, increasing age, male sex, hypertension, dyslipidemia, alcohol and hyperferritinemia. Increasing evidence support the role of pancreatic fat in the development of type 2 diabetes mellitus, MetS, atherosclerosis, severe acute pancreatitis and even pancreatic cancer. Evidence exists that fatty pancreas could be used as the initial indicator of "ectopic fat deposition", which is a key element of nonalcoholic fatty liver disease and/or MetS. Moreover, in patients with fatty pancreas, pancreaticoduodenectomy is associated with an increased risk of intraoperative blood loss and post-operative pancreatic fistula. PMID:27678349

  16. [Adult Refsum disease. A retinal dystrophy with therapeutic options].

    PubMed

    Rüther, K

    2005-08-01

    Adult Refsum disease is one of the few forms of tapetoretinal degenerations accessible for therapy. The disease is characterized by an elevated plasma phytanic acid level and high concentrations of phytanic acid in a variety tissues. Beside tapetoretinal degeneration, additional symptoms are chronic polyneuropathy, cerebellar ataxia, sensorineural hearing loss, anosmia, ichthyosis, skeletal malformations, and cardiac abnormalities. A diet low in phytanic acid leads to an amelioration of polyneuropathy and ataxia and slows or even stops the other manifestations. This beneficial effect of dietary precautions requires the need to get hold of as much patients as possible but better all of them. The ophthalmologist plays a crucial role to this end because of the early manifestation of the tapetoretinal degeneration. A delay of 11 years between the appearance of first symptoms and the diagnosis of Refsum disease, as reported in the literature, is not acceptable.

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

    PubMed

    Sanduzzi Zamparelli, Marco; Compare, Debora; Coccoli, Pietro; Rocco, Alba; Nardone, Olga Maria; Marrone, Giuseppe; Gasbarrini, Antonio; Grieco, Antonio; Nardone, Gerardo; Miele, Luca

    2016-01-01

    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. PMID:27483246

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

    PubMed Central

    Sanduzzi Zamparelli, Marco; Compare, Debora; Coccoli, Pietro; Rocco, Alba; Nardone, Olga Maria; Marrone, Giuseppe; Gasbarrini, Antonio; Grieco, Antonio; Nardone, Gerardo; Miele, Luca

    2016-01-01

    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. PMID:27483246

  19. Nutrition in early life and the programming of adult disease: a review.

    PubMed

    Langley-Evans, S C

    2015-01-01

    Foetal development and infancy are life stages that are characterised by rapid growth, development and maturation of organs and systems. Variation in the quality or quantity of nutrients consumed by mothers during pregnancy, or infants during the first year of life, can exert permanent and powerful effects upon developing tissues. These effects are termed 'programming' and represent an important risk factor for noncommunicable diseases of adulthood, including the metabolic syndrome and coronary heart disease. This narrative review provides an overview of the evidence-base showing that indicators of nutritional deficit in pregnancy are associated with a greater risk of type-2 diabetes and cardiovascular mortality. There is also a limited evidence-base that suggests some relationship between breastfeeding and the timing and type of foods used in weaning, and disease in later life. Many of the associations reported between indicators of early growth and adult disease appear to interact with specific genotypes. This supports the idea that programming is one of several cumulative influences upon health and disease acting across the lifespan. Experimental studies have provided important clues to the mechanisms that link nutritional challenges in early life to disease in adulthood. It is suggested that nutritional programming is a product of the altered expression of genes that regulate the cell cycle, resulting in effective remodelling of tissue structure and functionality. The observation that traits programmed by nutritional exposures in foetal life can be transmitted to further generations adds weight the argument that heritable epigenetic modifications play a critical role in nutritional programming.

  20. Therapeutic manipulation of glucocorticoid metabolism in cardiovascular disease

    PubMed Central

    Hadoke, Patrick WF; Iqbal, Javaid; Walker, Brian R

    2009-01-01

    The therapeutic potential for manipulation of glucocorticoid metabolism in cardiovascular disease was revolutionized by the recognition that access of glucocorticoids to their receptors is regulated in a tissue-specific manner by the isozymes of 11β-hydroxysteroid dehydrogenase. Selective inhibitors of 11β-hydroxysteroid dehydrogenase type 1 have been shown recently to ameliorate cardiovascular risk factors and inhibit the development of atherosclerosis. This article addresses the possibility that inhibition of 11β-hydroxsteroid dehydrogenase type 1 activity in cells of the cardiovascular system contributes to this beneficial action. The link between glucocorticoids and cardiovascular disease is complex as glucocorticoid excess is linked with increased cardiovascular events but glucocorticoid administration can reduce atherogenesis and restenosis in animal models. There is considerable evidence that glucocorticoids can interact directly with cells of the cardiovascular system to alter their function and structure and the inflammatory response to injury. These actions may be regulated by glucocorticoid and/or mineralocorticoid receptors but are also dependent on the 11β-hydroxysteroid dehydrogenases which may be expressed in cardiac, vascular (endothelial, smooth muscle) and inflammatory (macrophages, neutrophils) cells. The activity of 11β-hydroxysteroid dehydrogenases in these cells is dependent upon differentiation state, the action of pro-inflammaotory cytokines and the influence of endogenous inhibitors (oxysterols, bile acids). Further investigations are required to clarify the link between glucocorticoid excess and cardiovascular events and to determine the mechanism through which glucocorticoid treatment inhibits atherosclerosis/restenosis. This will provide greater insights into the potential benefit of selective 11β-hydroxysteroid dehydrogenase inhibitors in treatment of cardiovascular disease. PMID:19239478

  1. Psychological risk factors and the metabolic syndrome in patients with coronary heart disease: Findings from the Heart and Soul Study

    PubMed Central

    Cohen, Beth E.; Panguluri, Praveen; Na, Beeya; Whooley, Mary A.

    2010-01-01

    Psychological factors, such as depression and anxiety, are independently associated with an increased risk of both diabetes mellitus and cardiovascular disease, but the reasons for these associations are unknown. We sought to determine whether psychological factors were associated with a greater prevalence of the metabolic syndrome in patients with coronary heart disease, and the extent to which such an association may be explained by socioeconomic status, health behaviors, and biological mediators. We conducted a cross-sectional study of 1024 outpatients with stable coronary heart disease. Psychological factors, including depressive and anxiety symptoms, hostility, anger, and optimism–pessimism, were assessed using validated standardized questionnaires. The presence or absence of the metabolic syndrome was determined using the criteria outlined by the National Cholesterol Education Program, Adult Treatment Panel III. Higher levels of depression, anger expression, hostility, and pessimism were significantly associated with increased prevalence of the metabolic syndrome. These associations were explained by differences in socioeconomic status and health behaviors. Additional adjustment for potential biological mediators had little impact. Further research is needed to determine whether addressing socioeconomic and behavioral factors in people with depression or high levels of anger or hostility could reduce the burden of the metabolic syndrome. PMID:19969373

  2. Genetic and Environmental Regulation on Longitudinal Change of Metabolic Phenotypes in Danish and Chinese Adult Twins

    PubMed Central

    Li, Shuxia; Kyvik, Kirsten Ohm; Pang, Zengchang; Zhang, Dongfeng; Duan, Haiping; Tan, Qihua; Hjelmborg, Jacob; Kruse, Torben; Dalgård, Christine

    2016-01-01

    Objective The rate of change in metabolic phenotypes can be highly indicative of metabolic disorders and disorder-related modifications. We analyzed data from longitudinal twin studies on multiple metabolic phenotypes in Danish and Chinese twins representing two populations of distinct ethnic, cultural, social-economic backgrounds and geographical environments. Materials and Methods The study covered a relatively large sample of 502 pairs of Danish adult twins followed up for a long period of 12 years with a mean age at intake of 38 years (range: 18–65) and a total of 181 Chinese adult twin pairs traced for about 7 years with a mean baseline age of 39.5 years (range: 23–64). The classical twin models were fitted to the longitudinal change in each phenotype (Δphenotype) to estimate the genetic and environmental contributions to the variation in Δphenotype. Results Moderate to high contributions by the unique environment were estimated for all phenotypes in both Danish (from 0.51 for low density lipoprotein cholesterol up to 0.72 for triglycerides) and Chinese (from 0.41 for triglycerides up to 0.73 for diastolic blood pressure) twins; low to moderate genetic components were estimated for long-term change in most of the phenotypes in Danish twins except for triglycerides and hip circumference. Compared with Danish twins, the Chinese twins tended to have higher genetic control over the longitudinal changes in lipids (except high density lipoprotein cholesterol) and glucose, higher unique environmental contribution to blood pressure but no genetic contribution to longitudinal change in body mass traits. Conclusion Our results emphasize the major contribution of unique environment to the observed intra-individual variation in all metabolic phenotypes in both samples, and meanwhile reveal differential patterns of genetic and common environmental regulation on changes over time in metabolic phenotypes across the two samples. PMID:26862898

  3. Does Lysosomial Acid Lipase Reduction Play a Role in Adult Non-Alcoholic Fatty Liver Disease?

    PubMed Central

    Baratta, Francesco; Pastori, Daniele; Polimeni, Licia; Tozzi, Giulia; Violi, Francesco; Angelico, Francesco; Del Ben, Maria

    2015-01-01

    Lysosomal Acid Lipase (LAL) is a key enzyme involved in lipid metabolism, responsible for hydrolysing the cholesteryl esters and triglycerides. Wolman Disease represents the early onset phenotype of LAL deficiency rapidly leading to death. Cholesterol Ester Storage Disease is a late onset phenotype that occurs with fatty liver, elevated aminotransferase levels, hepatomegaly and dyslipidaemia, the latter characterized by elevated LDL-C and low HDL-C. The natural history and the clinical manifestations of the LAL deficiency in adults are not well defined, and the diagnosis is often incidental. LAL deficiency has been suggested as an under-recognized cause of dyslipidaemia and fatty liver. Therefore, LAL activity may be reduced also in non-obese patients presenting non-alcoholic fatty liver disease (NAFLD), unexplained persistently elevated liver transaminases or with elevation in LDL cholesterol. In these patients, it could be indicated to test LAL activity. So far, very few studies have been performed to assess LAL activity in representative samples of normal subjects or patients with NAFLD. Moreover, no large study has been carried out in adult subjects with NAFLD or cryptogenic cirrhosis. PMID:26602919

  4. Excessive Consumption of Green Tea as a Risk Factor for Periodontal Disease among Korean Adults

    PubMed Central

    Han, Kyungdo; Hwang, Eunkyung; Park, Jun-Beom

    2016-01-01

    This study was performed to assess the relationship between the amount of green tea that is consumed and periodontitis. It is based on data obtained from the Korea National Health and Nutrition Examination Survey, conducted between 2008 and 2010. A community periodontal index equal to code 3 was defined as moderate periodontitis, and code 4 was defined as severe periodontitis (n = 16,726). Consumption of green tea less than one cup per day was associated with a decreased prevalence of periodontal disease among Korean adults. The association between the consumption of green tea and periodontal disease was independent of various potential confounding factors, such as age, sex, body mass index, smoking, drinking, exercise, metabolic syndrome, frequency of tooth brushing per day, use of secondary oral products, the number of dental examination per year, diabetes, hypertension, and white blood cell count. Adjusted odds ratio and 95% confidence interval of no consumption was 1.360 (1.156, 1.601) when participants with consumption of two times per week ≤ x < 7 times per week was considered as a reference. However, consumption of one or more cups per day increased the prevalence of moderate and severe periodontitis. In conclusion, excessive consumption of green tea may be considered as a risk factor for periodontal disease among Korean adults. PMID:27384581

  5. Excessive Consumption of Green Tea as a Risk Factor for Periodontal Disease among Korean Adults.

    PubMed

    Han, Kyungdo; Hwang, Eunkyung; Park, Jun-Beom

    2016-01-01

    This study was performed to assess the relationship between the amount of green tea that is consumed and periodontitis. It is based on data obtained from the Korea National Health and Nutrition Examination Survey, conducted between 2008 and 2010. A community periodontal index equal to code 3 was defined as moderate periodontitis, and code 4 was defined as severe periodontitis (n = 16,726). Consumption of green tea less than one cup per day was associated with a decreased prevalence of periodontal disease among Korean adults. The association between the consumption of green tea and periodontal disease was independent of various potential confounding factors, such as age, sex, body mass index, smoking, drinking, exercise, metabolic syndrome, frequency of tooth brushing per day, use of secondary oral products, the number of dental examination per year, diabetes, hypertension, and white blood cell count. Adjusted odds ratio and 95% confidence interval of no consumption was 1.360 (1.156, 1.601) when participants with consumption of two times per week ≤ x < 7 times per week was considered as a reference. However, consumption of one or more cups per day increased the prevalence of moderate and severe periodontitis. In conclusion, excessive consumption of green tea may be considered as a risk factor for periodontal disease among Korean adults. PMID:27384581

  6. Maternal Fructose Exposure Programs Metabolic Syndrome-Associated Bladder Overactivity in Young Adult Offspring

    PubMed Central

    Lee, Wei-Chia; Tain, You-Lin; Wu, Kay L. H.; Leu, Steve; Chan, Julie Y. H.

    2016-01-01

    Maternal fructose exposure (MFE) programs the development of metabolic syndrome (MetS) in young adult offspring. Epidemiological data indicate that MetS may increase the risks of overactive bladder (OAB) symptoms. However, it remains unknown whether MFE programs MetS-associated bladder dysfunction in adult offspring. Using Sprague-Dawley rats, we investigated the effects of MFE during pregnancy and lactation on developmental programming of MetS-associated bladder dysfunction. In addition, next generation sequencing technology was used to identify potential transcripts involved in the programmed bladder dysfunction in adult male offspring to MFE. We found that MFE programmed the MetS-associated OAB symptoms (i.e., an increase in micturition frequency and a shortened mean inter-contractile interval) in young adult male offspring, alongside significant alterations in bladder transcripts, including Chrm2, Chrm3, P2rx1, Trpv4, and Vipr2 gene expression. At protein level, the expressions of M2-, M3-muscarinic and P2X1 receptor proteins were upregulated in the MFE bladder. Functionally, the carbachol-induced detrusor contractility was reduced in the MFE offspring. These data suggest that alterations in the bladder transcripts and impairment of the bladder cholinergic pathways may underlie the pathophysiology of programmed bladder dysfunction in adult offspring to MFE. PMID:27703194

  7. Validity of muscle-to-fat ratio as a predictor of adult metabolic syndrome

    PubMed Central

    Park, Jongsuk; Kim, Sangho

    2016-01-01

    [Purpose] This study was aimed at determining the validity of the muscle-to-fat ratio as an indicator for the prevention and management of metabolic syndrome by establishing an optimal cutoff value. [Subjects and Methods] Data from the first and second year of the fifth Korea National Health Nutrition Examination Survey, conducted by the Korean Ministry of Health and Welfare and Korean Centers for Disease Control and Prevention, were used. A total of 6,256 subjects were included in the study. Diagnostic accuracy was measured by using the area under the receiver operating characteristic curve. [Results] The receiver operating characteristic curve for the muscle-to-fat ratio, which represents the diagnostic power for predicting metabolic syndrome, was 0.713 in men and 0.721 in women. The optimal cutoff value for the prediction and diagnosis of metabolic syndrome was 3.09 kg/kg in men and 1.83 kg/kg in women. Intergroup differences based on the muscle-to-fat ratio indicated that the low-ratio group had higher values for all indicators of metabolic syndrome than the high-ratio group. [Conclusion] The muscle-to-fat ratio can be used as an indicator for the prediction and diagnosis of metabolic syndrome, and early prevention and management of metabolic syndrome can help in improving public health. PMID:27134408

  8. Effect of Natural Polyphenols on CYP Metabolism: Implications for Diseases.

    PubMed

    Korobkova, Ekaterina A

    2015-07-20

    Cytochromes P450 (CYPs) are a large group of hemeproteins located on mitochondrial membranes or the endoplasmic reticulum. They play a crucial role in the metabolism of endogenous and exogenous molecules. The activity of CYP is associated with a number of factors including redox potential, protein conformation, the accessibility of the active site by substrates, and others. This activity may be potentially modulated by a variety of small molecules. Extensive experimental data collected over the past decade point at the active role of natural polyphenols in modulating the catalytic activity of CYP. Polyphenols are widespread micronutrients present in human diets of plant origin and in medicinal herbs. These compounds may alter the activity of CYP either via direct interactions with the enzymes or by affecting CYP gene expression. The polyphenol-CYP interactions may significantly alter the pharmacokinetics of drugs and thus influence the effectiveness of chemical therapies used in the treatment of different types of cancers, diabetes, obesity, and cardiovascular diseases (CVD). CYPs are involved in the oxidation and activation of external carcinogenic agents, in which case the inhibition of the CYP activity is beneficial for health. CYPs also support detoxification processes. In this case, it is the upregulation of CYP genes that would be favorable for the organism. A CYP enzyme aromatase catalyzes the formation of estrone and estradiol from their precursors. CYPs also catalyze multiple reactions leading to the oxidation of estrogen. Estrogen signaling and oxidative metabolism of estrogen are associated with the development of cancer. Thus, polyphenol-mediated modulation of the CYP's activity also plays a vital role in estrogen carcinogenesis. The aim of the present review is to summarize the data collected over the last five to six years on the following topics: (1) the mechanisms of the interactions of CYP with food constituents that occur via the direct binding of

  9. Brain lipoprotein metabolism and its relation to neurodegenerative disease.

    PubMed

    Danik, M; Champagne, D; Petit-Turcotte, C; Beffert, U; Poirier, J

    1999-01-01

    notion and suggests that the isolated brain possesses its own system to maintain local lipid homeostasis. This is further exemplified by the salvage and recycling of lipids shown to occur following a lesion in order to allow surviving neurons to sprout and reestablish lost synapses. Not much is currently known about lipoprotein metabolism in neurodegenerative diseases, but lipid alterations have been repeatedly reported in Alzheimer brains in which neuronal loss and deafferentation are major features. Although the mechanism underlying the link between the epsilon4 allele of the apolipoprotein E gene and Alzheimer's disease is presently unclear, it may well be postulated that it is related to disturbances in brain lipoprotein metabolism. PMID:11028681

  10. Effect of Natural Polyphenols on CYP Metabolism: Implications for Diseases.

    PubMed

    Korobkova, Ekaterina A

    2015-07-20

    Cytochromes P450 (CYPs) are a large group of hemeproteins located on mitochondrial membranes or the endoplasmic reticulum. They play a crucial role in the metabolism of endogenous and exogenous molecules. The activity of CYP is associated with a number of factors including redox potential, protein conformation, the accessibility of the active site by substrates, and others. This activity may be potentially modulated by a variety of small molecules. Extensive experimental data collected over the past decade point at the active role of natural polyphenols in modulating the catalytic activity of CYP. Polyphenols are widespread micronutrients present in human diets of plant origin and in medicinal herbs. These compounds may alter the activity of CYP either via direct interactions with the enzymes or by affecting CYP gene expression. The polyphenol-CYP interactions may significantly alter the pharmacokinetics of drugs and thus influence the effectiveness of chemical therapies used in the treatment of different types of cancers, diabetes, obesity, and cardiovascular diseases (CVD). CYPs are involved in the oxidation and activation of external carcinogenic agents, in which case the inhibition of the CYP activity is beneficial for health. CYPs also support detoxification processes. In this case, it is the upregulation of CYP genes that would be favorable for the organism. A CYP enzyme aromatase catalyzes the formation of estrone and estradiol from their precursors. CYPs also catalyze multiple reactions leading to the oxidation of estrogen. Estrogen signaling and oxidative metabolism of estrogen are associated with the development of cancer. Thus, polyphenol-mediated modulation of the CYP's activity also plays a vital role in estrogen carcinogenesis. The aim of the present review is to summarize the data collected over the last five to six years on the following topics: (1) the mechanisms of the interactions of CYP with food constituents that occur via the direct binding of

  11. Cited2 is required for the maintenance of glycolytic metabolism in adult hematopoietic stem cells.

    PubMed

    Du, Jinwei; Li, Qiang; Tang, Fangqiang; Puchowitz, Michelle A; Fujioka, Hisashi; Dunwoodie, Sally L; Danielpour, David; Yang, Yu-Chung

    2014-01-15

    Mammalian adult hematopoietic stem cells (HSCs) reside in the hypoxic bone marrow microenvironment and display a distinct metabolic phenotype compared with their progenitors. It has been proposed that HSCs generate energy mainly through anaerobic glycolysis in a pyruvate dehydrogenase kinase (Pdk)-dependent manner. Cited2 is an essential regulator for HSC quiescence, apoptosis, and function. Herein, we show that conditional deletion of Cited2 in murine HSCs results in elevated levels of reactive oxygen species, decreased cellular glutathione content, increased mitochondrial activity, and decreased glycolysis. At the molecular level, Cited2 deficiency significantly reduced the expression of genes involved in metabolism, such as Pdk2, Pdk4, and lactate dehydrogenases B and D (LDHB and LDHD). Cited2-deficient HSCs also exhibited increased Akt signaling, concomitant with elevated mTORC1 activity and phosphorylation of FoxOs. Further, inhibition of PI3/Akt, but not mTORC1, partially rescued the repression of Pdk4 caused by deletion of Cited2. Altogether, our results suggest that Cited2 is required for the maintenance of adult HSC glycolytic metabolism likely through regulating Pdk2, Pdk4, LDHB, LDHD, and Akt activity. PMID:24083546

  12. Predictive equations for the estimation of basal metabolic rate in Malaysian adults.

    PubMed

    Ismail, M; Chee, S; Roslee, R; Zawiah, H

    1998-12-01

    In the field of human energy expenditure, the measurement of basal metabolic rate (BMR) is an essential element to derive energy requirement estimates for any given population. Besides basic anthropometrics data, this paper reports the generation of predictive equation for basal metabolic rates of healthy Malaysian adult from prospective measurements on 307 male and 349 females aged 18-60 years, using the Douglas bag technique. These new equations based on body-weight reveal that the current FAO/WHO/UNU (1985) predictive equations overestimate BMR of adult Malaysian by an average of 13% in males and 9% in female subjects while differences of between 4-5% were observed when compared to Henry and Rees (1991) equations for tropical people. There is a good reason to believe that the capacity to slow down metabolism amidst the hot and humid climate experience throughout the year as a genuine phenomenon for Malaysians. Similarly, these findings suggest that at equal energy intake recommendation for similar body weight, the lower energy needs of Malaysian could put them at greater risk for developing obesity. These observed deviations must be taken into account in formulating energy requirements of the population.

  13. The prevalence of periodontal diseases among adult population in Georgia.

    PubMed

    Tsitaishvili, L; Margvelashvili, M; Kalandadze, M; Margvelashvili, V

    2014-09-01

    The present research was conducted to estimate the prevalence of periodontal diseases in the adult population of Georgia, to study the peculiarity of their distribution within population in different regions of the country. The survey was carried out based on cluster- stratified method derived by WHO. 2370 adults including 1289 women and 1081 men distributed in 4 age groups: I - 20-34, II - 35-44, III - 45-64, IV - 65+ the residents of the city, town and village in 9 regions of Georgia and the capital Tbilisi were examined. The assessment of periodontal status and oral hygiene was based on WHO-'s recommendation. (WHO 1997 '˜Oral Health Assessment Form') Examination was done under good natural light using a mouth mirror and a periodontal index (CPI) probe for measurements of periodontal pockets depth. Questionnaires comprised questions for revealing the following risk factors: social status and family income, existence of common diseases, people'S attitude towards oral hygiene(tooth brushing, using dental floss, mouth rinsing) acceptability of dental service, sugar consumption rate, tobacco use, consumption of dairy products. The reliable statistical data received from the study relieved high prevalence of periodontal diseases in all regions: in Achara - 71.7, Mtskheta-Mtianeti - 70.8%, Imereti - 64.9%, Qvemo Qartli - 61.6%, Tbilisi - 61.8% and Shida Qartli - 60.5%, Guria - 55.9%, Samtskhe-Javakheti - 56.0%, Kakheti - 59.1%, Samegrelo - 55.2%. Despite the variability of risk factors high prevalence of inflammatory periodontal diseases in regions of Georgia was related to more extent to the low educational medical background, less dental acceptability due to not very positive attitude towards dental service and oral hygiene skills though financial problems also played substantial role. The study confirmed that periodontal diseases represent an actual problem in Georgia and need caring out serious preventive measures to enhance peoples' referral to dental service and

  14. The prevalence of periodontal diseases among adult population in Georgia.

    PubMed

    Tsitaishvili, L; Margvelashvili, M; Kalandadze, M; Margvelashvili, V

    2014-09-01

    The present research was conducted to estimate the prevalence of periodontal diseases in the adult population of Georgia, to study the peculiarity of their distribution within population in different regions of the country. The survey was carried out based on cluster- stratified method derived by WHO. 2370 adults including 1289 women and 1081 men distributed in 4 age groups: I - 20-34, II - 35-44, III - 45-64, IV - 65+ the residents of the city, town and village in 9 regions of Georgia and the capital Tbilisi were examined. The assessment of periodontal status and oral hygiene was based on WHO-'s recommendation. (WHO 1997 '˜Oral Health Assessment Form') Examination was done under good natural light using a mouth mirror and a periodontal index (CPI) probe for measurements of periodontal pockets depth. Questionnaires comprised questions for revealing the following risk factors: social status and family income, existence of common diseases, people'S attitude towards oral hygiene(tooth brushing, using dental floss, mouth rinsing) acceptability of dental service, sugar consumption rate, tobacco use, consumption of dairy products. The reliable statistical data received from the study relieved high prevalence of periodontal diseases in all regions: in Achara - 71.7, Mtskheta-Mtianeti - 70.8%, Imereti - 64.9%, Qvemo Qartli - 61.6%, Tbilisi - 61.8% and Shida Qartli - 60.5%, Guria - 55.9%, Samtskhe-Javakheti - 56.0%, Kakheti - 59.1%, Samegrelo - 55.2%. Despite the variability of risk factors high prevalence of inflammatory periodontal diseases in regions of Georgia was related to more extent to the low educational medical background, less dental acceptability due to not very positive attitude towards dental service and oral hygiene skills though financial problems also played substantial role. The study confirmed that periodontal diseases represent an actual problem in Georgia and need caring out serious preventive measures to enhance peoples' referral to dental service and

  15. Epilepsy in adults with mitochondrial disease: A cohort study

    PubMed Central

    Devine, Helen E.; Gorman, Grainne S.; Schaefer, Andrew M.; Horvath, Rita; Ng, Yi; Nesbitt, Victoria; Lax, Nichola Z.; McFarland, Robert; Cunningham, Mark O.; Taylor, Robert W.; Turnbull, Douglass M.

    2015-01-01

    Objective The aim of this work was to determine the prevalence and progression of epilepsy in adult patients with mitochondrial disease. Methods We prospectively recruited a cohort of 182 consecutive adult patients attending a specialized mitochondrial disease clinic in Newcastle upon Tyne between January 1, 2005 and January 1, 2008. We then followed this cohort over a 7‐year period, recording primary outcome measures of occurrence of first seizure, status epilepticus, stroke‐like episode, and death. Results Overall prevalence of epilepsy in the cohort was 23.1%. Mean age of epilepsy onset was 29.4 years. Prevalence varied widely between genotypes, with several genotypes having no cases of epilepsy, a prevalence of 34.9% in the most common genotype (m.3243A>G mutation), and 92.3% in the m.8344A>G mutation. Among the cohort as a whole, focal seizures, with or without progression to bilateral convulsive seizures, was the most common seizure type. Conversely, all of the patients with the m.8344A>G mutation and epilepsy experienced myoclonic seizures. Patients with the m.3243A>G mutation remain at high risk of developing stroke‐like episodes (1.16% per year). However, although the standardized mortality ratio for the entire cohort was high (2.86), this ratio did not differ significantly between patients with epilepsy (2.96) and those without (2.83). Interpretation Epilepsy is a common manifestation of mitochondrial disease. It develops early in the disease and, in the case of the m.3243A>G mutation, often presents in the context of a stroke‐like episode or status epilepticus. However, epilepsy does not itself appear to contribute to the increased mortality in mitochondrial disease. Ann Neurol 2015;78:949–957 PMID:26381753

  16. Effect of temperature on the standard metabolic rates of juvenile and adult Exopalaemon carinicauda

    NASA Astrophysics Data System (ADS)

    Zhang, Chengsong; Li, Fuhua; Xiang, Jianhai

    2015-03-01

    Ridgetail white prawn ( Exopalaemon carinicauda) are of significant economic importance in China where they are widely cultured. However, there is little information on the basic biology of this species. We evaluated the effect of temperature (16, 19, 22, 25, 28, 31, and 34°C) on the standard metabolic rates (SMRs) of juvenile and adult E. carinicauda in the laboratory under static conditions. The oxygen consumption rate (OCR), ammonia-N excretion rate (AER), and atomic ratio of oxygen consumed to nitrogen consumed (O:N ratio) of juvenile and adult E. carinicauda were significantly influenced by temperature ( P < 0.05). Both the OCR and AER of juveniles increased significantly with increasing temperature from 16 to 34°C, but the maximum OCR for adults was at 31°C. Juvenile shrimp exhibited a higher OCR than the adults from 19 to 34°C. There was no significant difference between the AERs of the two life-stages from 16 to 31°C ( P >0.05). The O:N ratio in juveniles was significantly higher than that in the adults over the entire temperature range ( P <0.05). The temperature coefficient ( Q 10) of OCR and AER ranged from 5.03 to 0.86 and 6.30 to 0.85 for the adults, respectively, and from 6.09-1.03 and 3.66-1.80 for the juveniles, respectively. The optimal temperature range for growth of the juvenile and adult shrimp was from 28 to 31°C, based on Q 10 and SMR values. Results from the present study may be used to guide pond culture production of E. carinicauda.

  17. [Attitude of hemophilic adult individuals towards their disease].

    PubMed

    Carruyo-Vizcaíno, Cecilia; Vizcaíno, Gilberto; Carrizo, Edgardo; Arteaga-Vizcaíno, Melvis; Sarmiento, Sandra; Vizcaíno-Carruyo, Jennifer

    2004-09-01

    The mental health of hemophilic individuals and their families play an important role on the integral treatment of the disease. The knowledge of the beliefs and attitudes perceived by the patients toward their disease will make possible a positive influence in their clinical improvement, their response to the treatment, as well as their quality of life. On the basis of the Azjen and Fishbein's Theory of Reasoned Action, a questionnaire was applied to 43 adult hemophilics to determine the salient beliefs about their disease. These beliefs permitted to elaborate a main structured questionnaire named Attitude Model in Patients with Hemophilia (Modelo de Actitud en Pacientes con Hemofilia, MAPACHE, in spanish), which was administered to the individuals and thus, the attitude toward their disease was obtained. Seventy two percent (72%) gave a major importance to the clinical aspects of the disease (hemorrhage, joint discomfort and trauma), 40% knew the general concepts of hemophilia (heredity, care and seriousness of the disease), 20% mentioned the implications of the psychosocial factors and only 18% had knowledge concerning the coagulation factors deficiency and the appropriate treatment. The MAPACHE showed a slightly positive score attitude (4.44 +/- 1.12 SEM) towards the disease in the majority of the groups (74.5%); with 26% of the hemophilics with a negative attitude. There were no significant differences between attitude and clinical parameters. It is recommended that a multidisciplinary team of caregivers should focus their efforts toward education and preventive measures in order to avoid the complications and consequences of the disease, to make possible a better quality of life in individuals with hemophilia.

  18. Dietary fatty acids in metabolic syndrome, diabetes and cardiovascular diseases.

    PubMed

    Cascio, Giuseppe; Schiera, Gabriella; Di Liegro, Italia

    2012-01-01

    In the last few decades, the prevalence of overweight and essential obesity has been undergoing a fast and progressive worldwide increase. Obesity has been in turn linked to type II diabetes, with the total number of diabetic patients worryingly increasing, in the last fifteen years, suggesting a pandemic phenomenon. At the same time, an increase in the prevalence of cardiovascular diseases has been also recorded. Increasing evidence suggests that the diet is involved in such escalation. In particular, the progressive globalization of food industry allowed massive supply, at a relatively low price, of a great variety of pre-packed food and bakery products, with very high energy content. Most of this food contains high amounts of saturated fatty acids (SFA) and of hydrogenated or trans fatty acids (TFA), that probably represent the prominent risk factors in the diet. Herein we will report diffusion and possible impact on health of such molecules, with reference to coronary heart disease, insulin resistance, metabolic syndrome and diabetes. We will also discuss the cellular and molecular mechanisms of action of fatty acids and fatty acid-derivatives which have been involved either in promoting or in preventing human pathologies. Free fatty acids (FFA) are not indeed only essential fuels for the organism. They also act as ligands for both membrane and nuclear receptors involved in different signaling pathways. Notably, some of these pathways can induce cell stress and apoptosis. Most important, FFA can affect glucose-induced insulin secretion and activate β-cell death. These events can be at least in part counteracted by polyunsaturated fatty acids. PMID:22414056

  19. Gold nanoparticles alter parameters of oxidative stress and energy metabolism in organs of adult rats.

    PubMed

    Ferreira, Gabriela Kozuchovski; Cardoso, Eria; Vuolo, Francieli Silva; Michels, Monique; Zanoni, Elton Torres; Carvalho-Silva, Milena; Gomes, Lara Mezari; Dal-Pizzol, Felipe; Rezin, Gislaine Tezza; Streck, Emilio L; Paula, Marcos Marques da Silva

    2015-12-01

    This study evaluated the parameters of oxidative stress and energy metabolism after the acute and long-term administration of gold nanoparticles (GNPs, 10 and 30 nm in diameter) in different organs of rats. Adult male Wistar rats received a single intraperitoneal injection or repeated injections (once daily for 28 days) of saline solution, GNPs-10 or GNPs-30. Twenty-four hours after the last administration, the animals were killed, and the liver, kidney, and heart were isolated for biochemical analysis. We demonstrated that acute administration of GNPs-30 increased the TBARS levels, and that GNPs-10 increased the carbonyl protein levels. The long-term administration of GNPs-10 increased the TBARS levels, and the carbonyl protein levels were increased by GNPs-30. Acute administration of GNPs-10 and GNPs-30 increased SOD activity. Long-term administration of GNPs-30 increased SOD activity. Acute administration of GNPs-10 decreased the activity of CAT, whereas long-term administration of GNP-10 and GNP-30 altered CAT activity randomly. Our results also demonstrated that acute GNPs-30 administration decreased energy metabolism, especially in the liver and heart. Long-term GNPs-10 administration increased energy metabolism in the liver and decreased energy metabolism in the kidney and heart, whereas long-term GNPs-30 administration increased energy metabolism in the heart. The results of our study are consistent with other studies conducted in our research group and reinforce the fact that GNPs can lead to oxidative damage, which is responsible for DNA damage and alterations in energy metabolism. PMID:26583437

  20. Increasing metabolic rate despite declining body weight in an adult parasitoid wasp.

    PubMed

    Casas, Jérôme; Body, Mélanie; Gutzwiller, Florence; Giron, David; Lazzari, Claudio R; Pincebourde, Sylvain; Richard, Romain; Llandres, Ana L

    2015-08-01

    Metabolic rate is a positive function of body weight, a rule valid for most organisms and the basis of several theories of metabolic ecology. For adult insects, however, the diversity of relationships between body mass and respiration remains unexplained. The aim of this study is to relate the respiratory metabolism of a parasitoid with body weight and foraging activity. We compared the metabolic rate of groups of starving and host-fed females of the parasitoid Eupelmus vuilleti recorded with respirometry for 7days, corresponding to the mean lifetime of starving females and over half of the lifetime of foraging females. The dynamics of carbohydrate, lipid and protein in the body of foraging females were quantified with biochemical techniques. Body mass and all body nutrients declined sharply from the first day onwards. By contrast, the CO2 produced and the O2 consumed increased steadily. Starving females showed the opposite trend, identifying foraging as the reason for the respiration increase of feeding females. Two complementary physiological processes explain the unexpected relationship between increasing metabolic rate and declining body weight. First, host hemolymph is a highly unbalanced food, and the excess nutrients (protein and carbohydrate) need to be voided, partially through excretion and partially through respiration. Second, a foraging young female produces eggs at an increasing rate during the first half of its lifetime, a process that also increases respiration. We posit that the time-varying metabolic rate contributions of the feeding and reproductive processes supplements the contribution of the structural mass and lead to the observed trend. We extend our explanations to other insect groups and discuss the potential for unification using Dynamic Energy Budget theory.

  1. Gold nanoparticles alter parameters of oxidative stress and energy metabolism in organs of adult rats.

    PubMed

    Ferreira, Gabriela Kozuchovski; Cardoso, Eria; Vuolo, Francieli Silva; Michels, Monique; Zanoni, Elton Torres; Carvalho-Silva, Milena; Gomes, Lara Mezari; Dal-Pizzol, Felipe; Rezin, Gislaine Tezza; Streck, Emilio L; Paula, Marcos Marques da Silva

    2015-12-01

    This study evaluated the parameters of oxidative stress and energy metabolism after the acute and long-term administration of gold nanoparticles (GNPs, 10 and 30 nm in diameter) in different organs of rats. Adult male Wistar rats received a single intraperitoneal injection or repeated injections (once daily for 28 days) of saline solution, GNPs-10 or GNPs-30. Twenty-four hours after the last administration, the animals were killed, and the liver, kidney, and heart were isolated for biochemical analysis. We demonstrated that acute administration of GNPs-30 increased the TBARS levels, and that GNPs-10 increased the carbonyl protein levels. The long-term administration of GNPs-10 increased the TBARS levels, and the carbonyl protein levels were increased by GNPs-30. Acute administration of GNPs-10 and GNPs-30 increased SOD activity. Long-term administration of GNPs-30 increased SOD activity. Acute administration of GNPs-10 decreased the activity of CAT, whereas long-term administration of GNP-10 and GNP-30 altered CAT activity randomly. Our results also demonstrated that acute GNPs-30 administration decreased energy metabolism, especially in the liver and heart. Long-term GNPs-10 administration increased energy metabolism in the liver and decreased energy metabolism in the kidney and heart, whereas long-term GNPs-30 administration increased energy metabolism in the heart. The results of our study are consistent with other studies conducted in our research group and reinforce the fact that GNPs can lead to oxidative damage, which is responsible for DNA damage and alterations in energy metabolism.

  2. Exploring the metabolic syndrome: Nonalcoholic fatty pancreas disease

    PubMed Central

    Catanzaro, Roberto; Cuffari, Biagio; Italia, Angelo; Marotta, Francesco

    2016-01-01

    After the first description of fatty pancreas in 1933, the effects of pancreatic steatosis have been poorly investigated, compared with that of the liver. However, the interest of research is increasing. Fat accumulation, associated with obesity and the metabolic syndrome (MetS), has been defined as “fatty infiltration” or “nonalcoholic fatty pancreas disease” (NAFPD). The term “fatty replacement” describes a distinct phenomenon characterized by death of acinar cells and replacement by adipose tissue. Risk factors for developing NAFPD include obesity, increasing age, male sex, hypertension, dyslipidemia, alcohol and hyperferritinemia. Increasing evidence support the role of pancreatic fat in the development of type 2 diabetes mellitus, MetS, atherosclerosis, severe acute pancreatitis and even pancreatic cancer. Evidence exists that fatty pancreas could be used as the initial indicator of “ectopic fat deposition”, which is a key element of nonalcoholic fatty liver disease and/or MetS. Moreover, in patients with fatty pancreas, pancreaticoduodenectomy is associated with an increased risk of intraoperative blood loss and post-operative pancreatic fistula. PMID:27678349

  3. Glycolipid and Ganglioside Metabolism Imbalances In Huntington’s Disease

    PubMed Central

    Desplats, Paula A.; Denny, Christine A.; Kass, Kristi E.; Gilmartin, Tim; Head, Steven R.; Sutcliffe, J. Gregor; Seyfried, Thomas N.; Thomas, Elizabeth A.

    2007-01-01

    We have explored genome-wide expression of genes related to glycobiology in exon 1 transgenic Huntington’s disease (HD) mice using a custom designed GLYCOv2 chip and Affymetrix microarray analyses. We validated, using quantitative real-time PCR, abnormal expression levels of genes encoding glycosyltransferases in the striatum of R6/1 transgenic mice, as well as in postmortem caudate from human HD patients. Many of these genes show differential regional expression within the CNS, as indicated by in situ hybridization analysis, suggesting region-specific regulation of this system in the brain. We further show disrupted patterns of glycolipids (acidic and neutral lipids) and/or ganglioside levels in both the forebrain of the R6/1 transgenic mice and caudate samples from human HD subjects. These findings reveal novel disruptions in glycolipid/ganglioside metabolic pathways in the pathology of HD and suggest that the development of new targets to restore glycosphingolipid balance may act to ameliorate some symptoms in HD. PMID:17600724

  4. Exploring the metabolic syndrome: Nonalcoholic fatty pancreas disease

    PubMed Central

    Catanzaro, Roberto; Cuffari, Biagio; Italia, Angelo; Marotta, Francesco

    2016-01-01

    After the first description of fatty pancreas in 1933, the effects of pancreatic steatosis have been poorly investigated, compared with that of the liver. However, the interest of research is increasing. Fat accumulation, associated with obesity and the metabolic syndrome (MetS), has been defined as “fatty infiltration” or “nonalcoholic fatty pancreas disease” (NAFPD). The term “fatty replacement” describes a distinct phenomenon characterized by death of acinar cells and replacement by adipose tissue. Risk factors for developing NAFPD include obesity, increasing age, male sex, hypertension, dyslipidemia, alcohol and hyperferritinemia. Increasing evidence support the role of pancreatic fat in the development of type 2 diabetes mellitus, MetS, atherosclerosis, severe acute pancreatitis and even pancreatic cancer. Evidence exists that fatty pancreas could be used as the initial indicator of “ectopic fat deposition”, which is a key element of nonalcoholic fatty liver disease and/or MetS. Moreover, in patients with fatty pancreas, pancreaticoduodenectomy is associated with an increased risk of intraoperative blood loss and post-operative pancreatic fistula.

  5. Mitochondrial response to nutrient availability and its role in metabolic disease.

    PubMed

    Gao, Arwen W; Cantó, Carles; Houtkooper, Riekelt H

    2014-05-01

    Metabolic inflexibility is defined as an impaired capacity to switch between different energy substrates and is a hallmark of insulin resistance and type 2 diabetes mellitus (T2DM). Hence, understanding the mechanisms underlying proper metabolic flexibility is key to prevent the development of metabolic disease and physiological deterioration. An important downstream player in the effects of metabolic flexibility is the mitochondrion. The objective of this review was to describe how mitochondrial metabolism adapts to limited nutrient situations or caloric excess by changes in mitochondrial function or biogenesis, as well as to define the mechanisms propelling these changes. Altogether, this should pinpoint key regulatory points by which metabolic flexibility might be ameliorated in situations of metabolic disease. PMID:24623376

  6. Mitochondrial response to nutrient availability and its role in metabolic disease

    PubMed Central

    Gao, Arwen W; Cantó, Carles; Houtkooper, Riekelt H

    2014-01-01

    Metabolic inflexibility is defined as an impaired capacity to switch between different energy substrates and is a hallmark of insulin resistance and type 2 diabetes mellitus (T2DM). Hence, understanding the mechanisms underlying proper metabolic flexibility is key to prevent the development of metabolic disease and physiological deterioration. An important downstream player in the effects of metabolic flexibility is the mitochondrion. The objective of this review was to describe how mitochondrial metabolism adapts to limited nutrient situations or caloric excess by changes in mitochondrial function or biogenesis, as well as to define the mechanisms propelling these changes. Altogether, this should pinpoint key regulatory points by which metabolic flexibility might be ameliorated in situations of metabolic disease. PMID:24623376

  7. Membrane transporters in a human genome-scale metabolic knowledgebase and their implications for disease

    PubMed Central

    Sahoo, Swagatika; Aurich, Maike K.; Jonsson, Jon J.; Thiele, Ines

    2014-01-01

    Membrane transporters enable efficient cellular metabolism, aid in nutrient sensing, and have been associated with various diseases, such as obesity and cancer. Genome-scale metabolic network reconstructions capture genomic, physiological, and biochemical knowledge of a target organism, along with a detailed representation of the cellular metabolite transport mechanisms. Since the first reconstruction of human metabolism, Recon 1, published in 2007, progress has been made in the field of metabolite transport. Recently, we published an updated reconstruction, Recon 2, which significantly improved the metabolic coverage and functionality. Human metabolic reconstructions have been used to investigate the role of metabolism in disease and to predict biomarkers and drug targets. Given the importance of cellular transport systems in understanding human metabolism in health and disease, we analyzed the coverage of transport systems for various metabolite classes in Recon 2. We will review the current knowledge on transporters (i.e., their preferred substrates, transport mechanisms, metabolic relevance, and disease association for each metabolite class). We will assess missing coverage and propose modifications and additions through a transport module that is functional when combined with Recon 2. This information will be valuable for further refinements. These data will also provide starting points for further experiments by highlighting areas of incomplete knowledge. This review represents the first comprehensive overview of the transporters involved in central metabolism and their transport mechanisms, thus serving as a compendium of metabolite transporters specific for human metabolic reconstructions. PMID:24653705

  8. Predictors of Alzheimer's Disease Caregiver Depression and Burden: What Noncaregiving Adults Can Learn from Active Caregivers

    ERIC Educational Resources Information Center

    Hayslip, Bert, Jr.; Han, GiBaeg; Anderson, Cristina L.

    2008-01-01

    This study examined similarities and differences between active caregivers (adult children and spouses whose family member had Alzheimer's disease) and not-as-yet caregiving adults (adult children and spouses whose family members are older, but do not as yet suffer from Alzheimer's disease). The objective was to determine what factors predict…

  9. Essential nutrient supplementation prevents heritable metabolic disease in multigenerational intrauterine growth-restricted rats

    PubMed Central

    Goodspeed, Danielle; Seferovic, Maxim D.; Holland, William; Mcknight, Robert A.; Summers, Scott A.; Branch, D. Ware; Lane, Robert H.; Aagaard, Kjersti M.

    2015-01-01

    Intrauterine growth restriction (IUGR) confers heritable alterations in DNA methylation, rendering risk of adult metabolic syndrome (MetS). Because CpG methylation is coupled to intake of essential nutrients along the one-carbon pathway, we reasoned that essential nutrient supplementation (ENS) may abrogate IUGR-conferred multigenerational MetS. Pregnant Sprague-Dawley rats underwent bilateral uterine artery ligation causing IUGR in F1. Among the F2 generation, IUGR lineage rats were underweight at birth (6.7 vs. 8.0 g, P < 0.0001) and obese by adulthood (p160: 613 vs. 510 g; P < 0.0001). Dual energy X-ray absorptiometry studies revealed increased central fat mass (Δ+40 g), accompanied by dyslipidemic (>30% elevated, P < 0.05) serum triglycerides (139 mg/dl), very-LDLs (27.8 mg/dl), and fatty acids (632 µM). Hyperglycemic-euglycemic clamp studies and glucose tolerance testing revealed insulin resistance. Conversely, IUGR lineage ENS-fed rats did not manifest MetS, with significantly lower body weight (p160: 410 g), >5-fold less central fat mass, normal hepatic glucose efflux, and >70% reduced circulating triglycerides and very-LDLs compared with IUGR control-fed F2 offspring (P < 0.01). Moreover, increased methylation of the IGF-1 P2 transcriptional start site among IUGR lineage F2 offspring was reversed in ENS (P < 0.04). This is an initial demonstration that supplementation along the one-carbon pathway abrogates adult morbidity and associated epigenomic modifications of IGF-1 in a rodent model of multigenerational MetS.—Goodspeed, D., Seferovic, M. D., Holland, W., Mcknight, R. A., Summers, S. A., Branch, D. W., Lane, R. H., Aagaard, K. M. Essential nutrient supplementation prevents heritable metabolic disease in multigenerational intrauterine growth-restricted rats. PMID:25395450

  10. Polycystic kidney disease in adult Brazilian agoutis (Dasyprocta leporina).

    PubMed

    Müller, D W H; Szentiks, C A; Wibbelt, G

    2009-07-01

    During the last 21 years, 7 adult captive Brazilian agoutis (Dasyprocta leporina) from 4 different zoologic gardens were necropsied and histologically examined at the Leibniz Institute for Zoo and Wildlife Research, Berlin, Germany. All animals had polycystic kidney disease as the major pathologic change. Except in 1 case, no clinical signs were recognized prior to death. The animals had macroscopic bilateral alterations of the kidneys ranging from granulated surfaces to severe polycystic changes. Microscopic examination revealed multifocal to generalized, moderate to severe cystic dilatations of Bowman's capsules and renal tubules, moderate mesangial and capsular proliferation of the renal corpuscles, mild interstitial fibrosis, and mild to moderate interstitial lympho-plasmacytic infiltrations. Little information is known about the genetic relationships of these animals, but breeding practice indicates a high possibility of inbred agouti zoo populations in Germany. This is the first report on polycystic kidney disease in Brazilian agoutis with possible genetic background.

  11. Changes in Metabolic Hormones in Malaysian Young Adults following Helicobacter pylori Eradication

    PubMed Central

    Yap, Theresa Wan-Chen; Leow, Alex Hwong-Ruey; Azmi, Ahmad Najib; Francois, Fritz; Perez-Perez, Guillermo I; Blaser, Martin J.; Poh, Bee-Hoon; Loke, Mun-Fai; Goh, Khean-Lee; Vadivelu, Jamuna

    2015-01-01

    Background More than half of the world’s adults carry Helicobacter pylori. The eradication of H. pylori may affect the regulation of human metabolic hormones. The aim of this study was to evaluate the effect of H. pylori eradication on meal-associated changes in appetite-controlled insulinotropic and digestive hormones, and to assess post-eradication changes in body mass index as part of a currently on-going multicentre ESSAY (Eradication Study in Stable Adults/Youths) study. Methods We enrolled 29 H. pylori-positive young adult (18–30 year-old) volunteer subjects to evaluate the effect of H. pylori eradication on meal-associated changes on eight gastrointestinal hormones, using a multiplex bead assay. Changes in body mass index and anthropometric measurements were recorded, pre- and post-eradication therapy. Results Pre-prandial active amylin, total peptide YY (PYY) and pancreatic polypeptide (PP) levels were significantly elevated 12 months post-eradication compared with baseline (n = 18; Wilcoxon's signed rank test, p<0.05). Four of the post-prandial gut metabolic hormones levels (GLP-1, total PYY, active amylin, PP) were significantly higher 12 months post-eradication compared to baseline (n = 18; p<0.05). Following H. pylori eradication, the BMI and anthropometric values did not significantly change. Conclusions Our study indicates that H. pylori eradication was associated with long-term disturbance in three hormones (active amylin, PP and total PYY) both pre- and post-prandially and one hormone (GLP-1) post-prandially. Longer post-eradication monitoring is needed to investigate the long-term impact of the observed hormonal changes on metabolic homeostasis. PMID:26291794

  12. Clinical Research Priorities in Adult Congenital Heart Disease

    PubMed Central

    Cotts, Timothy; Khairy, Paul; Opotowsky, Alexander R.; John, Anitha S.; Valente, Anne Marie; Zaidi, Ali N.; Cook, Stephen C.; Aboulhosn, Jamil; Ting, Jennifer Grando; Gurvitz, Michelle; Landzberg, Michael J.; Verstappen, Amy; Kay, Joseph; Earing, Michael; Franklin, Wayne; Kogon, Brian; Broberg, Craig S.

    2014-01-01

    Background Adult congenital heart disease (ACHD) clinicians are hampered by the paucity of data to inform clinical decision-making. The objective of this study was to identify priorities for clinical research in ACHD. Methods A list of 45 research questions was developed by the Alliance for Adult Research in Congenital Cardiology (AARCC), compiled into a survey, and administered to ACHD providers. Patient input was sought via the Adult Congenital Heart Association at community meetings and online forums. The 25 top questions were sent to ACHD providers worldwide via an online survey. Each question was ranked based on perceived priority and weighted based on time spent in ACHD care. The top 10 topics identified are presented and discussed. Results The final online survey yielded 139 responses. Top priority questions related to tetralogy of Fallot (timing of pulmonary valve replacement and criteria for primary prevention ICDs), patients with systemic right ventricles (determining the optimal echocardiographic techniques for measuring right ventricular function, and indications for tricuspid valve replacement and primary prevention ICDs), and single ventricle/Fontan patients (role of pulmonary vasodilators, optimal anticoagulation, medical therapy for preservation of ventricular function, treatment for protein losing enteropathy). In addition, establishing criteria to refer ACHD patients for cardiac transplantation was deemed a priority. Conclusions The ACHD field is in need of prospective research to address fundamental clinical questions. It is hoped that this methodical consultation process will inform researchers and funding organizations about clinical research topics deemed to be of high priority. PMID:24411207

  13. Relationship between Serum Vitamin D Status and Metabolic Risk Factors among Korean Adults with Prediabetes

    PubMed Central

    Kwon, Han Na; Lim, Hyunjung

    2016-01-01

    Serum vitamin D status has been associated with prediabetes and metabolic syndrome. Evidence for the increased risk of metabolic disorders in individuals with prediabetes and a low vitamin D status is limited and uncertain. Furthermore, it has not been confirmed whether this possible relationship occurs in the Korean population. The aim of this study was to assess serum vitamin D status and to examine the relationship between serum vitamin D levels and metabolic risk factors in Korean adults with prediabetes. This cross-sectional study was conducted among 60 subjects aged 20–65 years. Participants had fasting glucose levels of 100 to 125 mg/dl. A questionnaire was used to assess vitamin D synthesis from sun exposure and a dietary intake examined using 3-days dietary records. Clinical and biochemical data were also collected. The 2009 harmonized definition of metabolic syndrome was used. Serum vitamin D levels were classified according to criteria from the 2011 Institute of Medicine report. The majority of subjects (75%) had a serum 25(OH)D level < 20 ng/ml, and among them, 31.1% were vitamin D deficiency (< 12 ng/ml). The proportion (42.9%) of subjects having low HDL-cholesterol was the highest among vitamin D deficiency (< 12 ng/ml) group (12 to < 20 ng/ml: 16.1%, ≥ 20 ng/ml: 6.7%). We observed an inverse relationship between 25(OH)D levels and TG, AI (β = -6.355, SE = 2.463; β = -0.020, SE = 0.008) after adjusted confounders. Korean adults with prediabetes were more likely to have low serum 25(OH)D levels. A sufficient 25(OH)D level may have possible beneficial effects on lipid profiles. PMID:27783655

  14. Vitamin E Status and Metabolism in Adult and Aged Aryl Hydrocarbon Receptor Null Mice

    PubMed Central

    Traber, Maret G.; Mustacich, Debbie J.; Sullivan, Laura C.; Leonard, Scott W.; Ahern-Rindell, Amelia; Kerkvliet, Nancy

    2009-01-01

    The aryl hydrocarbon receptor (AhR) is involved in regulation of mechanisms for detoxification of xenobiotics, as well as vitamin A metabolism. Vitamin E is a fat-soluble nutrient whose metabolism is initialized via the cytochrome P450 system. Thus, AhR absence could alter hepatic regulation of α-tocopherol metabolism. To test this hypothesis, we assessed vitamin E status in adult (2–5 m) and old (21–22 m), wildtype and AhR-null mice. Plasma α-tocopherol concentrations in AhR null mice (2.3 ± 1.2 μmol/L, n= 19) were lower than those of wildtype mice (3.2 ± 1.2, n=17, P=0.0131); those in old mice (3.2 ± 1.2, n= 20) were higher than those of adults (2.2 ± 1.0, n=16, p=0.0075). Hepatic α-tocopherol concentrations were not different between genotypes, but were nearly double in old (32 ± 8 nmol/g, n=20) as compared with adult mice (17 ± 2, n=16, p<0.0001). Hepatic Cyp3a concentrations in AhR-null mice were greater than those in wildtypes (p=0.0011). Genotype (p=0.0047), sex (p<0.0001) and age (p<0.0001) were significant modifiers of liver α-tocopherol metabolite (α-CEHC) concentrations. In general, Cyp3a concentrations correlated with hepatic α-tocopherol (r= 0.3957, p<0.05) and α-CEHC (r=0.4260, p<0.05) concentrations. Since there were no significant genotype differences in the hepatic α- or γ-tocopherol concentrations, AhR null mice did not have dramatically altered vitamin E metabolism. Since they did have higher hepatic α-CEHC concentrations, these data suggest metabolism was up-regulated in the AhR null mice in order to maintain the hepatic tocopherol concentrations similar to those of wildtypes. PMID:20153623

  15. Metabolic bone disease associated with total parenteral nutrition.

    PubMed

    Klein, G L; Coburn, J W

    1984-01-01

    Patients receiving long-term treatment with total parenteral nutrition often develop bony abnormalities characterized by patchy osteomalacia and low bone turnover. The patients present evidence of physiologic hypoparathyroidism, although low levels of iPTH cannot entirely explain the osteomalacia. Abnormally low serum levels of 1,25(OH)2-vitamin D have been demonstrated, but the significance of these reduced levels in the pathogenesis of the bone lesions is not defined. Aluminum has been detected in large quantities in the plasma, urine, and bone of some patients treated with TPN, and there is mounting evidence that aluminum may be associated with skeletal pathology, particularly osteomalacia. There is, however, no clear documentation that aluminum accumulation produces the skeletal lesions observed, although it could be a contributing factor. There has been the unusual empiric observation that the removal of vitamin D2 from the infusate is associated with a decrease in the quantity of unmineralized osteoid in TPN patients. A possible role of vitamin D2 in producing osteomalacia is not easy to understand since normal serum levels of 25(OH)-D2, the circulating form of vitamin D2, have been reported. The long-term consequences of intravenous nutritional support for many aspects of metabolism remain unknown. Administration into the systemic circulation of predetermined quantities of calcium and phosphorus via a route that bypasses their passage across the intestinal mucosa, the portal system and the liver may have adverse consequences. It is possible that bypassing homeostatic mechanisms may affect bone formation and metabolism or lead to alterations in vitamin D sterols. Alternatively, a deficiency of an essential trace metal or the accumulation of a toxic trace substance could be responsible for the bony abnormalities. Much remains to be clarified concerning calcium homeostasis and bone disease during total parenteral nutrition. Among various possible factors, it

  16. Disease burdens from environmental tobacco smoke in Korean adults.

    PubMed

    Heo, Seulkee; Lee, Jong-Tae

    2015-01-01

    In this study, we estimated the disease burdens attributable to environmental tobacco smoke (ETS) exposure in Korean adults in 2010 and analyzed the trend of that from 2005 to 2010. We obtained information on the study population from the 2010 Cause of Death Statistic and estimated the ETS-attributable fraction using data from the Korean Community Health Survey and the Korean National Health and Nutrition Examination Survey. The numbers of ETS-attributable deaths in female and male non-smokers were estimated to be 4.1 and 69.6% of the numbers of deaths attributable to current smoke, respectively. The deaths attributable to ETS were larger in female than in male non-smokers (710 vs. 420). The ETS-attributable deaths increased slightly in 2005-2008 but decreased in 2009-2010. The number of potential years of life lost from ETS was 9077.24 years in 2010. If there were no exposure to ETS in adult non-smokers, we would expect to see 1130 fewer deaths (9.9% of the deaths from current smoke). The results suggest that ETS poses considerable disease burdens for non-smokers, especially women, in Korea.

  17. Intracranial Hemodynamic Changes During Adult Moyamoya Disease Progression

    PubMed Central

    Kwag, Hyun-Jeong; Jeong, Dong-Wook; Lee, Suk Hoon; Kim, Dae Hyun

    2008-01-01

    Background and purpose This study evaluated the changes in blood flow velocity in the anterior and posterior intracranial circulations according to the progression of moyamoya disease in adult patients. Methods We evaluated Suzuki's angiographic stage and mean blood flow velocity (MBFV) changes in intracranial vessels from both sides in 19 adult moyamoya patients. We then analyzed the linearity of MBFV changes from early to late moyamoya stages in each intracranial vessel using piecewise linear regression models. Results The MBFV in the middle cerebral artery, terminal internal carotid artery, and anterior cerebral artery increased non linearly until stage III, and then decreased progressively up to stage VI. The ophthalmic artery also showed nonlinear velocity changes, with an increase in MBFV up to stage IV, followed by a decrease in MBFV up to stage VI. The MBFV of the basilar artery increased linearly from a normal velocity at an early moyamoya stage to a stenotic velocity at a late stage. There was no statistically significant regression model for the relationship between the MBFV in the posterior cerebral artery and moyamoya stage. Conclusions The nonlinear and/or linear MBFV changes associated with variable intracranial vessels might be useful in initial and follow-up evaluations of different stages of moyamoya disease. PMID:19513306

  18. Interorgan ammonia metabolism in health and disease: a surgeon's view.

    PubMed

    Souba, W W

    1987-01-01

    Ammonia is a toxic molecule that is the principal by-product of amino acid metabolism. Although the transport of ammonia in a nontoxic form protects the brain against high circulating levels, the interorgan transport of this molecule and the orchestration between tissues that has evolved is related primarily to the fact that the nitrogen molecule is an essential molecule for the maintenance of the body's nutrition economy and overall metabolic homeostasis. Efficient handling and disposal of ammonia requires a cooperative effort between tissues in order to maintain nitrogen homeostasis. The liver is the central organ of ammonia metabolism, but other organs also play a key role in the interorgan exchange of this molecule. Alterations in ammonia metabolism occur during critical illness. These changes are adaptive and are designed to maintain metabolic homeostasis. Interorgan cooperation in ammonia metabolism is necessary to insure the proper integration of the metabolic processes which contribute to and are essential for survival during critical illness. An understanding of these processes improves our knowledge of metabolic regulation and will lead to a rational approach to the nutritional and metabolic support provided to critically ill patients. PMID:3323556

  19. The clinical application of metabolic therapy for cardiovascular disease.

    PubMed

    Hadj, Anthony; Pepe, Salvatore; Rosenfeldt, Franklin

    2007-01-01

    Metabolic therapy involves the administration of a substance normally found in the body to enhance a metabolic reaction within the cell. This may be achieved in two ways. Firstly, for some systems a substance can be given to achieve greater than normal levels in the body so as to drive an enzymic reaction in a preferred direction. Secondly, metabolic therapy may be used to correct an absolute or relative deficiency of a cellular component. Thus, metabolic therapy differs greatly from most standard cardiovascular pharmacologic therapies such as the use of ACE Inhibitors, beta-blockers, statins and calcium channel antagonists that are given to block rather than enhance cellular processes.

  20. The clinical application of metabolic therapy for cardiovascular disease.

    PubMed

    Hadj, Anthony; Pepe, Salvatore; Rosenfeldt, Franklin

    2007-01-01

    Metabolic therapy involves the administration of a substance normally found in the body to enhance a metabolic reaction within the cell. This may be achieved in two ways. Firstly, for some systems a substance can be given to achieve greater than normal levels in the body so as to drive an enzymic reaction in a preferred direction. Secondly, metabolic therapy may be used to correct an absolute or relative deficiency of a cellular component. Thus, metabolic therapy differs greatly from most standard cardiovascular pharmacologic therapies such as the use of ACE Inhibitors, beta-blockers, statins and calcium channel antagonists that are given to block rather than enhance cellular processes. PMID:17618830

  1. Increased Susceptibility to Metabolic Alterations in Young Adult Females Exposed to Early Malnutrition

    PubMed Central

    del Carmen Miñana-Solis, María; Escobar, Carolina

    2007-01-01

    Early malnutrition during gestation and lactation modifies growth and metabolism permanently. Follow up studies using a nutritional rehabilitation protocol have reported that early malnourished rats exhibit hyperglycemia and/or hyperinsulinemia, suggesting that the effects of early malnutrition are permanent and produce a “programming” effect on metabolism. Deleterious effects have mainly been observed when early-malnutrition is followed by a high-carbohydrate or a high-fat diet. The aim of this study was to evaluate whether following a balanced diet subsequent to malnutrition can deter the expression of metabolic disease and lead rats to exhibit metabolic responses, similar to those of well-nourished controls. Young rats, born from dams malnourished during gestation and lactation with a low protein diet, were provided with a regular balanced chow diet upon weaning. At 90 days of age, the effects of rehabilitation were determined under three different feeding conditions: ad libitum, fasting or fasting-reefed satiated. Early-malnourished rats showed an increased rate of body weight gain. Males under ad libitum conditions showed an elevated concentration of hepatic glycogen and low values of insulin. In the fasting-reefed satiated condition, only early-malnourished females showed an alteration in glucose response and glucagon level, compared with their well-nourished controls. Data indicate that a balanced diet along life after early malnutrition can mask the expression of metabolic disorders and that a metabolic challenges due to a prolonged fasting and reefed state unmask metabolic deficiencies in early-malnourished females. PMID:17200687

  2. Information system for the support of research, diagnosis and therapy of inborn metabolic diseases.

    PubMed

    Kauert, R; Töpel, T; Scholz, U; Hofestädt, R

    2001-01-01

    We developed an information system for inborn metabolic diseases. The system consists of three parts. The first part is the MD-Cave for information on laboratory findings, genes, enzymes and metabolic pathways. The second part (ASDB) concerns with active agents and their different mechanisms of action inside the metabolic pathway and possible therapeutic treatment of these illnesses. The third part deals with the integration of these and other data bases for easy access to different information. This information system can be helpful for scientists and physicians working in the field of inborn metabolic diseases.

  3. Prevalence of cardiovascular disease risk factors among older Puerto Rican adults living in Massachusetts.

    PubMed

    Van Rompay, Maria I; Castaneda-Sceppa, Carmen; McKeown, Nicola M; Ordovás, José M; Tucker, Katherine L

    2011-10-01

    There remains limited research on cardiovascular disease (CVD) risk factors in Puerto Rican adults. We compared lifestyle and CVD risk factors in Puerto Rican men and women with normal fasting glucose (NFG), impaired fasting glucose (IFG), or type 2 diabetes (T2D), and investigated achievement of American Diabetes Association (ADA) treatment goals in those with T2D. Baseline data from the Boston Puerto Rican Health Study were analyzed, which included 1,287 adults aged 45-75 years. Obesity, hyperglycemia, and dyslipidemia were prevalent and increased from NFG to IFG and T2D. In individuals without T2D, fasting insulin correlated significantly with body mass index. Achievement of ADA goals was poor; LDL cholesterol was most achieved (59.4%), followed by blood pressure (27.2%) and glycosylated hemoglobin (27.0%). Poverty, female sex, current alcohol use, and diabetes or anti-hypertensive medication use were associated with not meeting goals. Puerto Rican adults living in the Boston area showed several metabolic abnormalities and high CVD risk, likely due to pervasive obesity and socio-economic disparities.

  4. Physical fitness and the metabolic syndrome in adults from the Quebec Family Study.

    PubMed

    Boulé, Normand G; Bouchard, Claude; Tremblay, Angelo

    2005-04-01

    Physically fit individuals have a lower risk of cardiovascular disease and type 2 diabetes. However, it is unknown whether the associations between physical fitness and the metabolic syndrome are independent of total and abdominal adiposity. Physical fitness was defined as the physical work capacity on a cycle ergometer at heart rate of 150 bpm (PWC 150) in a sample of 158 men and 198 women 20-60 years of age. PWC 150 was adjusted for fat-free mass prior to the analyses. Percent body fat was estimated by hydrostatic weighing. Visceral and subcutaneous abdominal fat were measured by computed tomography. The prevalence of the metabolic syndrome was based on two definitions. The metabolic syndrome decreased with increasing fitness in men (approx. 6 times higher in less fit vs. most fit tertile, p < 0.05) and in women (approx. 4 times higher in less fit vs. most fit tertile, p < 0.05). Fitness was negatively associated with most individual components of the metabolic syndrome, except HDL-cholesterol for which the correlation was positive. However, in men and in women, the effects of physical fitness on the individual components of the metabolic syndrome were attenuated after considering total and abdominal adiposity. PMID:15981784

  5. Social burden and lifestyle in adults with congenital heart disease.

    PubMed

    Zomer, A Carla; Vaartjes, Ilonca; Uiterwaal, Cuno S P; van der Velde, Enno T; Sieswerda, Gert-Jan T; Wajon, Elly M C; Plomp, Koos; van Bergen, Paul F M; Verheugt, Carianne L; Krivka, Eva; de Vries, Cees J; Lok, Dirk J A; Grobbee, Diederick E; Mulder, Barbara J M

    2012-06-01

    We aimed to evaluate how the presence and severity of congenital heart disease (CHD) influence social life and lifestyle in adult patients. A random sample (n = 1,496) from the CONgenital CORvitia (n = 11,047), the Dutch national registry of adult patients with CHD, completed a questionnaire on educational attainment, employment and marital statuses, and lifestyle (response 76%). The Utrecht Health Project provided a large reference group (n = 6,810) of unaffected subjects. Logistic regression models were used for subgroup analyses and to adjust for age, gender, and socioeconomic status where appropriate. Of all patients 51.5% were men (median age 39 years, interquartile range 29 to 51) with mild (46%), moderate (44%), and severe (10%) CHD. Young (<40-year-old) patients with CHD were more likely to have achieved a lower education (adjusted odds ratios [ORs] 1.6 for men and 1.9 for women, p <0.05 for the 2 comparisons), significantly more often unemployed (adjusted ORs 5.9 and 2.0 for men and women, respectively), and less likely to be in a relationship compared to the reference group (adjusted ORs 8.5 for men and 4.5 for women). These poorer outcomes were seen in all severity groups. Overall, the CHD population smoked less (adjusted OR 0.5, p <0.05), had more sports participation (adjusted OR 1.2, p <0.05), and had less obesity (adjusted OR 0.7, p <0.05) than the reference group. In conclusion, there was a substantial social disadvantage in adult patients with CHD, which was seen in all severity groups and primarily in young men. In contrast, adults with CHD had healthier lifestyles compared to the reference group. PMID:22444325

  6. Eating habits of preschool children and the risk of obesity, insulin resistance and metabolic syndrome in adults.

    PubMed

    Kostecka, Małgorzata

    2014-01-01

    Background & Objective : Nutrient excess and nutrient deficiency in the diets of preschool children can lead to permanent modification of metabolic pathways and increased risk of diet-dependent diseases in adults. Children are most susceptible to the adverse consequences of bad eating habits.The objective of this study was to evaluate the eating habits and the diets of preschool children as risk factors for excessive weight, obesity, insulin resistance and the metabolic syndrome. Methods : The study was conducted on 350 randomly selected preschool children attending kindergartens in south-eastern Poland. Three-day dietary recalls were processed and evaluated in the Dieta 5 application. Results : The analyzed diets were characterized by low diversity and a high share of processed foods, such as pate, sausages, ketchup, mayonnaise, fried meat, French fries and fast-food. The dietary content of vegetables, raw fruit, dairy products and whole grain products was alarmingly low. Conclusions : Diets characterized by excessive energy value and nutritional deficiency can lead to health problems. In most cases, excessive weight gain in children can be blamed on parents and caretakers who are not aware of the health consequences of high-calorie foods rich in fats and sugar.

  7. Eating habits of preschool children and the risk of obesity, insulin resistance and metabolic syndrome in adults.

    PubMed

    Kostecka, Małgorzata

    2014-01-01

    Background & Objective : Nutrient excess and nutrient deficiency in the diets of preschool children can lead to permanent modification of metabolic pathways and increased risk of diet-dependent diseases in adults. Children are most susceptible to the adverse consequences of bad eating habits.The objective of this study was to evaluate the eating habits and the diets of preschool children as risk factors for excessive weight, obesity, insulin resistance and the metabolic syndrome. Methods : The study was conducted on 350 randomly selected preschool children attending kindergartens in south-eastern Poland. Three-day dietary recalls were processed and evaluated in the Dieta 5 application. Results : The analyzed diets were characterized by low diversity and a high share of processed foods, such as pate, sausages, ketchup, mayonnaise, fried meat, French fries and fast-food. The dietary content of vegetables, raw fruit, dairy products and whole grain products was alarmingly low. Conclusions : Diets characterized by excessive energy value and nutritional deficiency can lead to health problems. In most cases, excessive weight gain in children can be blamed on parents and caretakers who are not aware of the health consequences of high-calorie foods rich in fats and sugar. PMID:25674127

  8. Fetal origins of adult disease: epidemiology and mechanisms

    PubMed Central

    Byrne, C; Phillips, D

    2000-01-01

    The past 10 years have provided unequivocal evidence that there are associations between birth size measures and future development of adult diseases, such as type 2 diabetes and coronary artery disease. Despite initial concern that bias or residual confounding in the analyses had produced these rather bizarre associations, the findings have now been reproduced in different cohorts by independent investigators from many parts of the world. The challenge for the next decade must be to discover the cellular and molecular mechanisms giving rise to these associations. If this aim is accomplished, it might be possible to devise strategies to reduce the impact of these disabling, chronic, and expensive diseases. The purpose of this review is to describe some of the relevant, important, and more recent epidemiological studies, and also to discuss potential mechanisms underpinning the associations.J Clin Pathol(J Clin Pathol 2000;53:822–828) Key Words: atherosclerotic vascular disease • type 2 diabetes • birth weight PMID:11127263

  9. Intensity of bouted and sporadic physical activity and the metabolic syndrome in adults

    PubMed Central

    Robson, Jordan

    2015-01-01

    Background. Physical activity guidelines for adults only recognize the health benefits of accumulating bouted moderate-to-vigorous physical activity (MVPA), or MVPA occurring over at least 10 consecutive minutes. There is a lack of evidence supporting the health benefits of other patterns and intensities of activity including sporadic MVPA (i.e., MVPA occurring in periods of fewer than 10 consecutive minutes) and light intensity physical activity (LIPA). The objective of this study was to examine the health benefits associated with physical activity that does not meet the physical activity guidelines criteria for bouted MVPA. Specifically, we examined the association between sporadic MVPA and bouted and sporadic LIPA with the metabolic syndrome. Methods. We studied a representative cross-sectional sample of 1,974 adults aged 20 years and older from the 2003–2006 US National Health and Nutrition Examination Survey. Physical activity was measured over 7 days using Actigraph AM-7164 accelerometers. Each minute over the 7-day measurement period was classified as being of a sedentary, light, or moderate-to-vigorous intensity. A 10 min threshold differentiated bouted activity from sporadic activity. Average minutes/day of sporadic LIPA, sporadic MVPA, bouted LIPA, bouted MVPA, and embedded MVPA (MVPA occurring within bouts of primarily LIPA) were calculated. Metabolic syndrome status was determined using established criteria. Associations were examined using logistic regression and controlled for relevant covariates. Results. For every 30 min/day of physical activity, the odds ratio (95% confidence interval) of the metabolic syndrome was reduced by 4% (1–7%) for bouted LIPA, 64% (51–71%) for bouted MVPA, and 57% (45–67%) for embedded MVPA. Sporadic LIPA was not independently associated with the metabolic syndrome. We could not examine the association between sporadic MVPA and the metabolic syndrome because participants accumulated such a marginal amount of this

  10. Integrated analysis of transcript-level regulation of metabolism reveals disease-relevant nodes of the human metabolic network.

    PubMed

    Galhardo, Mafalda; Sinkkonen, Lasse; Berninger, Philipp; Lin, Jake; Sauter, Thomas; Heinäniemi, Merja

    2014-02-01

    Metabolic diseases and comorbidities represent an ever-growing epidemic where multiple cell types impact tissue homeostasis. Here, the link between the metabolic and gene regulatory networks was studied through experimental and computational analysis. Integrating gene regulation data with a human metabolic network prompted the establishment of an open-sourced web portal, IDARE (Integrated Data Nodes of Regulation), for visualizing various gene-related data in context of metabolic pathways. Motivated by increasing availability of deep sequencing studies, we obtained ChIP-seq data from widely studied human umbilical vein endothelial cells. Interestingly, we found that association of metabolic genes with multiple transcription factors (TFs) enriched disease-associated genes. To demonstrate further extensions enabled by examining these networks together, constraint-based modeling was applied to data from human preadipocyte differentiation. In parallel, data on gene expression, genome-wide ChIP-seq profiles for peroxisome proliferator-activated receptor (PPAR) γ, CCAAT/enhancer binding protein (CEBP) α, liver X receptor (LXR) and H3K4me3 and microRNA target identification for miR-27a, miR-29a and miR-222 were collected. Disease-relevant key nodes, including mitochondrial glycerol-3-phosphate acyltransferase (GPAM), were exposed from metabolic pathways predicted to change activity by focusing on association with multiple regulators. In both cell types, our analysis reveals the convergence of microRNAs and TFs within the branched chain amino acid (BCAA) metabolic pathway, possibly providing an explanation for its downregulation in obese and diabetic conditions.

  11. Integrated analysis of transcript-level regulation of metabolism reveals disease-relevant nodes of the human metabolic network

    PubMed Central

    Galhardo, Mafalda; Sinkkonen, Lasse; Berninger, Philipp; Lin, Jake; Sauter, Thomas; Heinäniemi, Merja

    2014-01-01

    Metabolic diseases and comorbidities represent an ever-growing epidemic where multiple cell types impact tissue homeostasis. Here, the link between the metabolic and gene regulatory networks was studied through experimental and computational analysis. Integrating gene regulation data with a human metabolic network prompted the establishment of an open-sourced web portal, IDARE (Integrated Data Nodes of Regulation), for visualizing various gene-related data in context of metabolic pathways. Motivated by increasing availability of deep sequencing studies, we obtained ChIP-seq data from widely studied human umbilical vein endothelial cells. Interestingly, we found that association of metabolic genes with multiple transcription factors (TFs) enriched disease-associated genes. To demonstrate further extensions enabled by examining these networks together, constraint-based modeling was applied to data from human preadipocyte differentiation. In parallel, data on gene expression, genome-wide ChIP-seq profiles for peroxisome proliferator-activated receptor (PPAR) γ, CCAAT/enhancer binding protein (CEBP) α, liver X receptor (LXR) and H3K4me3 and microRNA target identification for miR-27a, miR-29a and miR-222 were collected. Disease-relevant key nodes, including mitochondrial glycerol-3-phosphate acyltransferase (GPAM), were exposed from metabolic pathways predicted to change activity by focusing on association with multiple regulators. In both cell types, our analysis reveals the convergence of microRNAs and TFs within the branched chain amino acid (BCAA) metabolic pathway, possibly providing an explanation for its downregulation in obese and diabetic conditions. PMID:24198249

  12. Redox metabolism abnormalities in autistic children associated with mitochondrial disease.

    PubMed

    Frye, R E; Delatorre, R; Taylor, H; Slattery, J; Melnyk, S; Chowdhury, N; James, S J

    2013-06-18

    Research studies have uncovered several metabolic abnormalities associated with autism spectrum disorder (ASD), including mitochondrial disease (MD) and abnormal redox metabolism. Despite the close connection between mitochondrial dysfunction and oxidative stress, the relation between MD and oxidative stress in children with ASD has not been studied. Plasma markers of oxidative stress and measures of cognitive and language development and ASD behavior were obtained from 18 children diagnosed with ASD who met criteria for probable or definite MD per the Morava et al. criteria (ASD/MD) and 18 age and gender-matched ASD children without any biological markers or symptoms of MD (ASD/NoMD). Plasma measures of redox metabolism included reduced free glutathione (fGSH), oxidized glutathione (GSSG), the fGSH/GSSG ratio and 3-nitrotyrosine (3NT). In addition, a plasma measure of chronic immune activation, 3-chlorotyrosine (3CT), was also measured. Language was measured using the preschool language scale or the expressive one-word vocabulary test (depending on the age), adaptive behaviour was measured using the Vineland Adaptive Behavior Scale (VABS) and core autism symptoms were measured using the Autism Symptoms Questionnaire and the Social Responsiveness Scale. Children with ASD/MD were found to have lower scores on the communication and daily living skill subscales of the VABS despite having similar language and ASD symptoms. Children with ASD/MD demonstrated significantly higher levels of fGSH/GSSG and lower levels of GSSG as compared with children with ASD/NoMD, suggesting an overall more favourable glutathione redox status in the ASD/MD group. However, compare with controls, both ASD groups demonstrated lower fGSH and fGSH/GSSG, demonstrating that both groups suffer from redox abnormalities. Younger ASD/MD children had higher levels of 3CT than younger ASD/NoMD children because of an age-related effect in the ASD/MD group. Both ASD groups demonstrated significantly

  13. Fructose metabolism in the adult mouse optic nerve, a central white matter tract.

    PubMed

    Meakin, Paul J; Fowler, Maxine J; Rathbone, Alex J; Allen, Lynne M; Ransom, Bruce R; Ray, David E; Brown, Angus M

    2007-01-01

    Our recent report that fructose supported the metabolism of some, but not all axons, in the adult mouse optic nerve prompted us to investigate in detail fructose metabolism in this tissue, a typical central white matter tract, as these data imply efficient fructose metabolism in the central nervous system (CNS). In artificial cerebrospinal fluid containing 10 mmol/L glucose or 20 mmol/L fructose, the stimulus-evoked compound action potential (CAP) recorded from the optic nerve consisted of three stable peaks. Replacing 10 mmol/L glucose with 10 mmol/L fructose, however, caused delayed loss of the 1st CAP peak (the 2nd and 3rd CAP peaks were unaffected). Glycogen-derived metabolic substrate(s) temporarily sustained the 1st CAP peak in 10 mmol/L fructose, as depletion of tissue glycogen by a prior period of aglycaemia or high-frequency CAP discharge rendered fructose incapable of supporting the 1st CAP peak. Enzyme assays showed the presence of both hexokinase and fructokinase (both of which can phosphorylate fructose) in the optic nerve. In contrast, only hexokinase was expressed in cerebral cortex. Hexokinase in optic nerve had low affinity and low capacity with fructose as substrate, whereas fructokinase displayed high affinity and high capacity for fructose. These findings suggest an explanation for the curious fact that the fast conducting axons comprising the 1st peak of the CAP are not supported in 10 mmol/L fructose medium; these axons probably do not express fructokinase, a requirement for efficient fructose metabolism.

  14. Dysregulation of hepatic fatty acid metabolism in chronic kidney disease

    PubMed Central

    Jin, Kyubok; Norris, Keith; Vaziri, Nosratola D.

    2013-01-01

    Background Chronic kidney disease (CKD) results in hypertriglyceridemia which is largely due to impaired clearance of triglyceride-rich lipoproteins occasioned by downregulation of lipoprotein lipase and very low-density lipoprotein (LDL) receptor in the skeletal muscle and adipose tissue and of hepatic lipase and LDL receptor-related protein in the liver. However, data on the effect of CKD on fatty acid metabolism in the liver is limited and was investigated here. Methods Male Sprague-Dawley rats were randomized to undergo 5/6 nephrectomy (CRF) or sham operation (control) and observed for 12 weeks. The animals were then euthanized and their liver tissue tested for nuclear translocation (activation) of carbohydrate-responsive element binding protein (ChREBP) and sterol-responsive element binding protein-1 (SREBP-1) which independently regulate the expression of key enzyme in fatty acid synthesis, i.e. fatty acid synthase (FAS) and acyl-CoA carboxylase (ACC) as well as nuclear Peroxisome proliferator-activated receptor alpha (PPARα) which regulates the expression of enzymes involved in fatty acid oxidation and transport, i.e. L-FABP and CPT1A. In addition, the expression of ATP synthase α, ATP synthase β, glycogen synthase and diglyceride acyltransferase 1 (DGAT1) and DGAT2 were determined. Results Compared with controls, the CKD rats exhibited hypertriglyceridemia, elevated plasma and liver tissue free fatty acids, increased nuclear ChREBP and reduced nuclear SREBP-1 and PPARα, upregulation of ACC and FAS and downregulation of L-FABP, CPT1A, ATP synthase α, glycogen synthase and DGAT in the liver tissue. Conclusion Liver in animals with advanced CKD exhibits ChREBP-mediated upregulation of enzymes involved in fatty acid synthesis, downregulation of PPARα-regulated fatty acid oxidation system and reduction of DGAT resulting in reduced fatty acid incorporation in triglyceride. PMID:23045433

  15. Influence of metabolic syndrome on arterial stiffness and its age-related change in young adults: the Bogalusa Heart Study.

    PubMed

    Li, Shengxu; Chen, Wei; Srinivasan, Sathanur R; Berenson, Gerald S

    2005-06-01

    Increased arterial stiffness is associated with risk variables of metabolic syndrome in middle-aged and older adults. However, information regarding the influence of the metabolic syndrome on arterial stiffness and its rate of change with age in young adults is limited. These aspects were examined in a sample of 806 asymptomatic, healthy young adults aged 24-44 years from a black-white community. Brachial to ankle pulse wave velocity (baPWV) measured by an oscillometric method was used as an index of arterial stiffness. baPWV increased with the increasing number of metabolic syndrome components, defined by National Cholesterol Education Program Adult Treatment Panel III (1256, 1314, and 1422 cm/s for those with 0, 1-2, and 3-5 components, respectively, P for trend <0.001). Furthermore, the rate of change (slope) of baPWV with age increased as the number of metabolic syndrome components increased (4.1, 10.7, and 18.7 cm/s per year for those with 0, 1-2, and 3-5 components, respectively; P for comparison of slopes <0.001). These findings by showing the deleterious effects of metabolic syndrome on arterial stiffness and its age-related increase in young adults underscore the importance of this syndrome in cardiovascular risk assessment even in a younger population. Further longitudinal studies are needed to confirm the current cross-sectional findings.

  16. Obesity: The Metabolic Disease, Advances on Drug Discovery and Natural Product Research.

    PubMed

    Castro, Mafalda; Preto, Marco; Vasconcelos, Vitor; Urbatzka, Ralph

    2016-01-01

    Obesity is a global health threat. OECD reported that more than half (52%) of the adult population in the European Union is overweight or obese. Obesity and obesity-related co-morbidities have deep negative effects on morbidity, mortality, professional and personal quality of life. Healthcare costs represent a negative impact of this disease, with an associated economic cost of 100 billion US$ per year in the United States. The most prescribed drugs for obesity treatment worldwide are orlistat, and phentermine/topiramate extended release, while the major prescribed drug for the same disease in the US are exenatide and dapagliflozin. The so far developed drugs, targeting weight loss, have a long history of malignant secondary effects. There is still a lack of efficient and safe drugs to treat obesity and related metabolic complications since in many cases cure cannot be reached by bariatric surgery or healthy lifestyle habits. Terrestrial and aquatic organisms are a promising source of valuable, bioactive compounds, often with interest for human health. Some of the natural compounds or organisms have been used for centuries by humans as traditional medicine foods. In this review, we give insights into the adipose tissue function and development, and the progress in traditional anti-obesity pharmacotherapy. A major focus is to highlight the state of the art of natural compounds with anti-obesity properties and their potential as candidates for drug development; an overview is given about natural compounds derived from different marine animal sources, cyanobacteria, marine phytoplankton, fungus or plants. PMID:27086785

  17. Obesity: The Metabolic Disease, Advances on Drug Discovery and Natural Product Research.

    PubMed

    Castro, Mafalda; Preto, Marco; Vasconcelos, Vitor; Urbatzka, Ralph

    2016-01-01

    Obesity is a global health threat. OECD reported that more than half (52%) of the adult population in the European Union is overweight or obese. Obesity and obesity-related co-morbidities have deep negative effects on morbidity, mortality, professional and personal quality of life. Healthcare costs represent a negative impact of this disease, with an associated economic cost of 100 billion US$ per year in the United States. The most prescribed drugs for obesity treatment worldwide are orlistat, and phentermine/topiramate extended release, while the major prescribed drug for the same disease in the US are exenatide and dapagliflozin. The so far developed drugs, targeting weight loss, have a long history of malignant secondary effects. There is still a lack of efficient and safe drugs to treat obesity and related metabolic complications since in many cases cure cannot be reached by bariatric surgery or healthy lifestyle habits. Terrestrial and aquatic organisms are a promising source of valuable, bioactive compounds, often with interest for human health. Some of the natural compounds or organisms have been used for centuries by humans as traditional medicine foods. In this review, we give insights into the adipose tissue function and development, and the progress in traditional anti-obesity pharmacotherapy. A major focus is to highlight the state of the art of natural compounds with anti-obesity properties and their potential as candidates for drug development; an overview is given about natural compounds derived from different marine animal sources, cyanobacteria, marine phytoplankton, fungus or plants.

  18. Diagnostic and treatment implications of psychosis secondary to treatable metabolic disorders in adults: a systematic review

    PubMed Central

    2014-01-01

    Objective It is important for psychiatrists to be aware of certain inborn errors of metabolism (IEMs) as these rare disorders can present as psychosis, and because definitive treatments may be available for treating the underlying metabolic cause. A systematic review was conducted to examine IEMs that often present with schizophrenia-like symptoms. Data sources Published literature on MEDLINE was assessed regarding diseases of homocysteine metabolism (DHM; cystathionine beta-synthase deficiency [CbS-D] and homocysteinemia due to methyltetrahydrofolate reductase deficiency [MTHFR-D]), urea cycle disorders (UCD), acute porphyria (POR), Wilson disease (WD), cerebrotendinous-xanthomatosis (CTX) and Niemann-Pick disease type C (NP-C). Study selection Case reports, case series or reviews with original data regarding psychiatric manifestations and cognitive impairment published between January 1967 and June 2012 were included based on a standardized four-step selection process. Data extraction All selected articles were evaluated for descriptions of psychiatric signs (type, severity, natural history and treatment) in addition to key disease features. Results A total of 611 records were identified. Information from CbS-D (n = 2), MTHFR-D (n = 3), UCD (n = 8), POR (n = 12), WD (n = 11), CTX (n = 14) and NP-C publications (n = 9) were evaluated. Six non-systematic literature review publications were also included. In general, published reports did not provide explicit descriptions of psychiatric symptoms. The literature search findings are presented with a didactic perspective, showing key features for each disease and psychiatric signs that should trigger psychiatrists to suspect that psychotic symptoms may be secondary to an IEM. Conclusion IEMs with a psychiatric presentation and a lack of, or sub-clinical, neurological signs are rare, but should be considered in patients with atypical psychiatric symptoms. PMID:24775716

  19. Adult lactose digestion status and effects on disease

    PubMed Central

    Szilagyi, Andrew

    2015-01-01

    BACKGROUND: Adult assimilation of lactose divides humans into dominant lactase-persistent and recessive nonpersistent phenotypes. OBJECTIVES: To review three medical parameters of lactose digestion, namely: the changing concept of lactose intolerance; the possible impact on diseases of microbial adaptation in lactase-nonpersistent populations; and the possibility that the evolution of lactase has influenced some disease pattern distributions. METHODS: A PubMed, Google Scholar and manual review of articles were used to provide a narrative review of the topic. RESULTS: The concept of lactose intolerance is changing and merging with food intolerances. Microbial adaptation to regular lactose consumption in lactase-nonpersistent individuals is supported by limited evidence. There is evidence suggestive of a relationship among geographical distributions of latitude, sunhine exposure and lactase proportional distributions worldwide. DISCUSSION: The definition of lactose intolerance has shifted away from association with lactose maldigestion. Lactose sensitivity is described equally in lactose digesters and maldigesters. The important medical consequence of withholding dairy foods could have a detrimental impact on several diseases; in addition, microbial adaptation in lactase-nonpersistent populations may alter risk for some diseases. There is suggestive evidence that the emergence of lactase persistence, together with human migrations before and after the emergence of lactase persistence, have impacted modern-day diseases. CONCLUSIONS: Lactose maldigestion and lactose intolerance are not synonymous. Withholding dairy foods is a poor method to treat lactose intolerance. Further epidemiological work could shed light on the possible effects of microbial adaptation in lactose maldigesters. The evolutionary impact of lactase may be still ongoing. PMID:25855879

  20. Urinary uromodulin, kidney function and cardiovascular disease in elderly adults

    PubMed Central

    Garimella, Pranav S.; Biggs, Mary L.; Katz, Ronit; Ix, Joachim H.; Bennett, Michael R.; Devarajan, Prasad; Kestenbaum, Bryan R.; Siscovick, David S.; Jensen, Majken K.; Shlipak, Michael G.; Chaves, Paulo H. M.; Sarnak, Mark J.

    2015-01-01

    Urinary uromodulin (uUMOD) is the most common secreted tubular protein in healthy adults. However, the relationship between uUMOD and clinical outcomes is still unclear. Here we measured uUMOD in 192 participants of the Cardiovascular Health Study with over a 30% decline in estimated glomerular filtration rate (eGFR) over 9 years, 54 with incident end stage renal disease (ESRD), and in a random sub-cohort of 958 participants. The association of uUMOD with eGFR decline was evaluated using logistic regression and with incident ESRD, cardiovascular disease, heart failure and mortality using Cox proportional regression. Mean age was 78 years and median uUMOD was 25.8 μg/mL. In a case-control study evaluating eGFR decline (192 cases and 231 controls), each standard deviation higher uUMOD was associated with a 23% lower odds of eGFR decline (odds ratio 0.77, (95% CI 0.62, 0.96)) and a 10% lower risk of mortality (hazard ratio 0.90, (95% CI 0.83, 0.98)) after adjusting for demographics, eGFR, albumin/creatinine ratio and other risk factors. There was no risk association of uUMOD with ESRD, cardiovascular disease or heart failure after multivariable adjustment. Thus, low uUMOD levels may identify persons at risk of progressive kidney disease and mortality above and beyond established markers of kidney disease, namely eGFR and the albumin/creatinine ratio. Future studies need to confirm these results and evaluate whether uUMOD is a marker of tubular health and/or whether it plays a causal role in preserving kidney function. PMID:26154925

  1. The role of the complement system in metabolic organs and metabolic diseases.

    PubMed

    Phieler, Julia; Garcia-Martin, Ruben; Lambris, John D; Chavakis, Triantafyllos

    2013-02-01

    Emerging evidence points to a close crosstalk between metabolic organs and innate immunity in the course of metabolic disorders. In particular, cellular and humoral factors of innate immunity are thought to contribute to metabolic dysregulation of the adipose tissue or the liver, as well as to dysfunction of the pancreas; all these conditions are linked to the development of insulin resistance and diabetes mellitus. A central component of innate immunity is the complement system. Interestingly, the classical view of complement as a major system of host defense that copes with infections is changing to that of a multi-functional player in tissue homeostasis, degeneration, and regeneration. In the present review, we will discuss the link between complement and metabolic organs, focusing on the pancreas, adipose tissue, and liver and the diverse effects of complement system on metabolic disorders.

  2. Is cancer a disease of abnormal cellular metabolism?

    PubMed Central

    DeBerardinis, Ralph J.

    2009-01-01

    In the 1920s, Otto Warburg observed that tumor cells consume a large amount of glucose, much more than normal cells, and convert most of it to lactic acid. This phenomenon, now known as the ‘Warburg effect,’ is the foundation of one of the earliest general concepts of cancer: that a fundamental disturbance of cellular metabolic activity is at the root of tumor formation and growth. In the ensuing decades, as it became apparent that abnormalities in chromosomes and eventually individual genes caused cancer, the ‘metabolic’ model of cancer lost a good deal of its appeal, even as emerging technologies were exploiting the Warburg effect clinically to detect tumors in vivo. We now know that tumor suppressors and proto-oncogenes influence metabolism, and that mutations in these genes can promote a metabolic phenotype supporting cell growth and proliferation. Thus, these advances have unified aspects of the metabolic and genetic models of cancer, and have stimulated a renewed interest in the role of cellular metabolism in tumorigenesis. This review reappraises the notion that dysregulated cellular metabolism is a key feature of cancer, and discusses some metabolic issues that have escaped scrutiny over the years and now deserve closer attention. PMID:18941420

  3. Is the Mouse a Good Model of Human PPARγ-Related Metabolic Diseases?

    PubMed

    Pap, Attila; Cuaranta-Monroy, Ixchelt; Peloquin, Matthew; Nagy, Laszlo

    2016-01-01

    With the increasing number of patients affected with metabolic diseases such as type 2 diabetes, obesity, atherosclerosis and insulin resistance, academic researchers and pharmaceutical companies are eager to better understand metabolic syndrome and develop new drugs for its treatment. Many studies have focused on the nuclear receptor peroxisome proliferator-activated receptor gamma (PPARγ), which plays a crucial role in adipogenesis and lipid metabolism. These studies have been able to connect this transcription factor to several human metabolic diseases. Due to obvious limitations concerning experimentation in humans, animal models-mainly mouse models-have been generated to investigate the role of PPARγ in different tissues. This review focuses on the metabolic features of human and mouse PPARγ-related diseases and the utility of the mouse as a model. PMID:27483259

  4. Is the Mouse a Good Model of Human PPARγ-Related Metabolic Diseases?

    PubMed Central

    Pap, Attila; Cuaranta-Monroy, Ixchelt; Peloquin, Matthew; Nagy, Laszlo

    2016-01-01

    With the increasing number of patients affected with metabolic diseases such as type 2 diabetes, obesity, atherosclerosis and insulin resistance, academic researchers and pharmaceutical companies are eager to better understand metabolic syndrome and develop new drugs for its treatment. Many studies have focused on the nuclear receptor peroxisome proliferator-activated receptor gamma (PPARγ), which plays a crucial role in adipogenesis and lipid metabolism. These studies have been able to connect this transcription factor to several human metabolic diseases. Due to obvious limitations concerning experimentation in humans, animal models—mainly mouse models—have been generated to investigate the role of PPARγ in different tissues. This review focuses on the metabolic features of human and mouse PPARγ-related diseases and the utility of the mouse as a model. PMID:27483259

  5. Rituximab in adult minimal change disease and focal segmental glomerulosclerosis.

    PubMed

    Kronbichler, Andreas; Bruchfeld, Annette

    2014-01-01

    Treatment of nephrotic syndrome due to minimal change disease and focal segmental glomerulosclerosis remains a challenge since steroid dependence, steroid resistance and a relapsing disease course exhibits a high cumulative steroid dosage. The necessity of using alternative steroid-sparing immunosuppressive agents with potential toxic side effects also restricts their long-term use. Rituximab, a monoclonal antibody targeting CD20, has been increasingly used in the therapy of difficult-to-treat nephrotic syndrome. A clinical response has been shown for patients with steroid-dependent or frequently relapsing nephrotic syndrome, whereas the benefit seems to be limited in steroid-resistant patients, especially those with underlying focal segmental glomerulosclerosis. No potentially life-threatening adverse events have been observed in the treatment of adult minimal change disease and focal segmental glomerulosclerosis following rituximab administration. Since most reports are retrospective and evidence of efficacy is derived from small case series, more prospective trials in a controlled, randomized manner are highly desirable to delineate the use of rituximab or other B cell-depleting agents in steroid-dependent, frequently relapsing or steroid-resistant patients.

  6. Adolescents and Adults with Congenital Heart Diseases in Oman

    PubMed Central

    Al-Balushi, Asim; Al-Kindi, Hamood; Al-Shuaili, Hamood; Kumar, Suresh; Al-Maskari, Salim

    2015-01-01

    Objectives The aim of our study was to examine the spectrum, demographics, and mortality rate among adolescents and adults with congenital heart diseases (CHD) in Oman. Methods Data was collected retrospectively from the Royal Hospital, Muscat, electronic health records for all patients with a diagnosis of CHD aged 13 years and above. Data was analyzed according to the type of CHD and in-hospital mortality was assessed using Kaplan-Meier survival analysis. Results A total of 600 patients with CHD were identified, among them 145 (24%) were aged 18 years or below. The median age was 24 years. The majority of patients had a simple form of CHD. Atrial and ventricular septal defects together constituted 62.8% of congenital heart diseases. Most patients were clustered in Muscat (32%) and the Batinah regions (31.1%) of Oman. Patients with tetralogy of Fallot and Fontan had shorter survival time than recorded in the published literature. Conclusion Mostly simple forms of CHD in younger patients was observed. The survival rate was significantly shortened in more complex lesions compared to simple lesions. A national data registry for CHD is needed to address the morbidities and mortality associated with the disease. PMID:25829997

  7. Frailty: A Vital Sign for Older Adults With Cardiovascular Disease.

    PubMed

    Forman, Daniel E; Alexander, Karen P

    2016-09-01

    Mechanisms of aging predispose to cardiovascular disease (CVD), as well as to aggregate health challenges. For older adults, CVD is likely to exist in combination with comorbid conditions, disability, polypharmacy, falling risks, and body composition changes. These other dimensions of health result in cumulative weakening with greater clinical complexity that confound basic precepts of CVD presentation, prognosis, and treatments. A convenient operational tool is needed to gauge this age-related vulnerability such that it can be integrated in the evaluation and treatment of CVD. Frailty is a concept that is neither disease- nor age-specific, but is used to characterize the reserve that a person has available to tolerate stresses associated with aging, disease, and even therapy. Frailty arises from specific biological mechanisms in association with cumulative physiological decrements, psychosocial stresses, and physical impairments. Performance-based and survey tools have been developed and tested to measure frailty. Although different frailty tools vary in practicality, measured domains, and precise applications, all are useful in identifying risks that commonly accrue with age. Although comparisons between frailty tools are ongoing and sometimes even controversial, the rationale to integrate routine use of frailty screening as part of routine care is relatively straightforward and easy to envision. Frailty assessment applied as a vital sign (for standard maintenance and evaluation of new symptoms) enhances perspectives of risk, decision-making, and opportunities for tailored CVD management. PMID:27476987

  8. MJA Practice Essentials--Endocrinology. 9: Pituitary disease in adults.

    PubMed

    Hurley, David M; Ho, Ken K Y

    2004-04-19

    Pituitary adenomas are found in 10%-25% of unselected autopsy series and are evident in about 10% of asymptomatic individuals by magnetic resonance imaging. Diagnosis of pituitary disorders is often delayed by lack of awareness and the subtlety of symptoms and signs. Hypopituitarism is suspected when peripheral hormone concentrations are low without an elevation in the corresponding pituitary tropic hormone(s). Severe adult-onset growth-hormone deficiency results in reduced muscle mass, increased fat mass and diminished quality of life, which are reversed by growth hormone replacement therapy. While trans-sphenoidal surgery remains first-line treatment for acromegaly, drug treatment has an important role in controlling residual growth-hormone excess and, in some circumstances, as first-line treatment. Dopamine-agonist therapy (cabergoline or bromocriptine) is the treatment of choice for micro- and macroprolactinomas. In patients with suggestive clinical features, elevated 24-hour urine free cortisol level is usually sufficient to diagnose endogenous Cushing's syndrome; careful additional investigation is needed to determine whether the cause is Cushing's disease (pituitary adenoma secreting adrenocorticotropic hormone [ACTH]), ectopic ACTH secretion or adrenal disease. Heightened awareness is needed to detect the sometimes subtle symptoms and signs of pituitary disease

  9. Short-Term Treatment with Bisphenol-A Leads to Metabolic Abnormalities in Adult Male Mice

    PubMed Central

    Batista, Thiago M.; Alonso-Magdalena, Paloma; Vieira, Elaine; Amaral, Maria Esmeria C.; Cederroth, Christopher R.; Nef, Serge; Quesada, Ivan; Carneiro, Everardo M.; Nadal, Angel

    2012-01-01

    Bisphenol-A (BPA) is one of the most widespread endocrine disrupting chemicals (EDC) used as the base compound in the manufacture of polycarbonate plastics. Although evidence points to consider exposure to BPA as a risk factor for insulin resistance, its actions on whole body metabolism and on insulin-sensitive tissues are still unclear. The aim of the present work was to study the effects of low doses of BPA in insulin-sensitive peripheral tissues and whole body metabolism in adult mice. Adult mice were treated with subcutaneous injection of 100 µg/kg BPA or vehicle for 8 days. Whole body energy homeostasis was assessed with in vivo indirect calorimetry. Insulin signaling assays were conducted by western blot analysis. Mice treated with BPA were insulin resistant and had increased glucose-stimulated insulin release. BPA-treated mice had decreased food intake, lower body temperature and locomotor activity compared to control. In skeletal muscle, insulin-stimulated tyrosine phosphorylation of the insulin receptor β subunit was impaired in BPA-treated mice. This impairment was associated with a reduced insulin-stimulated Akt phosphorylation in the Thr308 residue. Both skeletal muscle and liver displayed an upregulation of IRS-1 protein by BPA. The mitogen-activated protein kinase (MAPK) signaling pathway was also impaired in the skeletal muscle from BPA-treated mice. In the liver, BPA effects were of lesser intensity with decreased insulin-stimulated tyrosine phosphorylation of the insulin receptor β subunit. In conclusion, short-term treatment with low doses of BPA slows down whole body energy metabolism and disrupts insulin signaling in peripheral tissues. Thus, our findings support the notion that BPA can be considered a risk factor for the development of type 2 diabetes. PMID:22470480

  10. Effect of exercise on fluoride metabolism in adult humans: a pilot study.

    PubMed

    V Zohoori, Fatemeh; Innerd, Alison; Azevedo, Liane B; Whitford, Gary M; Maguire, Anne

    2015-01-01

    An understanding of all aspects of fluoride metabolism is critical to identify its biological effects and avoid fluoride toxicity in humans. Fluoride metabolism and subsequently its body retention may be affected by physiological responses to acute exercise. This pilot study investigated the effect of exercise on plasma fluoride concentration, urinary fluoride excretion and fluoride renal clearance following no exercise and three exercise intensity conditions in nine healthy adults after taking a 1-mg Fluoride tablet. After no, light, moderate and vigorous exercise, respectively, the mean (SD) baseline-adjusted i) plasma fluoride concentration was 9.6(6.3), 11.4(6.3), 15.6(7.7) and 14.9(10.0) ng/ml; ii) rate of urinary fluoride excretion over 0-8 h was 46(15), 44(22), 34(17) and 36(17) μg/h; and iii) rate of fluoride renal clearance was 26.5(9.0), 27.2(30.4), 13.1(20.4) and 18.3(34.9) ml/min. The observed trend of a rise in plasma fluoride concentration and decline in rate of fluoride renal clearance with increasing exercise intensity needs to be investigated in a larger trial. This study, which provides the first data on the effect of exercise with different intensities on fluoride metabolism in humans, informs sample size planning for any subsequent definitive trial, by providing a robust estimate of the variability of the effect. PMID:26581340

  11. Weight for gestational age and metabolically healthy obesity in adults from the Haguenau cohort

    PubMed Central

    Matta, Joane; Carette, Claire; Levy Marchal, Claire; Bertrand, Julien; Pétéra, Mélanie; Zins, Marie; Pujos-Guillot, Estelle; Comte, Blandine; Czernichow, Sébastien

    2016-01-01

    Background An obesity subphenotype, named ‘metabolically healthy obese’ (MHO) has been recently defined to characterise a subgroup of obese individuals with less risk for cardiometabolic abnormalities. To date no data are available on participants born with small weight for gestational age (SGA) and the risk of metabolically unhealthy obesity (MUHO). Objective Assess the risk of MUHO in SGA versus appropriate for gestational age (AGA) adult participants. Methods 129 young obese individuals (body mass index ≥30 kg/m²) from data of an 8-year follow-up Haguenau cohort (France), were identified out of 1308 participants and were divided into 2 groups: SGA (n=72) and AGA (n=57). Metabolic characteristics were analysed and compared using unpaired t-test. The HOMA-IR index was determined for the population and divided into quartiles. Obese participants within the first 3 quartiles were considered as MHO and those in the fourth quartile as MUHO. Relative risks (RRs) and 95% CI for being MUHO in SGA versus AGA participants were computed. Results The SGA-obese group had a higher risk of MUHO versus the AGA-obese group: RR=1.27 (95% CI 1.10 to 1.6) independently of age and sex. Conclusions In case of obesity, SGA might confer a higher risk of MUHO compared with AGA. PMID:27580829

  12. Effect of exercise on fluoride metabolism in adult humans: a pilot study.

    PubMed

    V Zohoori, Fatemeh; Innerd, Alison; Azevedo, Liane B; Whitford, Gary M; Maguire, Anne

    2015-11-19

    An understanding of all aspects of fluoride metabolism is critical to identify its biological effects and avoid fluoride toxicity in humans. Fluoride metabolism and subsequently its body retention may be affected by physiological responses to acute exercise. This pilot study investigated the effect of exercise on plasma fluoride concentration, urinary fluoride excretion and fluoride renal clearance following no exercise and three exercise intensity conditions in nine healthy adults after taking a 1-mg Fluoride tablet. After no, light, moderate and vigorous exercise, respectively, the mean (SD) baseline-adjusted i) plasma fluoride concentration was 9.6(6.3), 11.4(6.3), 15.6(7.7) and 14.9(10.0) ng/ml; ii) rate of urinary fluoride excretion over 0-8 h was 46(15), 44(22), 34(17) and 36(17) μg/h; and iii) rate of fluoride renal clearance was 26.5(9.0), 27.2(30.4), 13.1(20.4) and 18.3(34.9) ml/min. The observed trend of a rise in plasma fluoride concentration and decline in rate of fluoride renal clearance with increasing exercise intensity needs to be investigated in a larger trial. This study, which provides the first data on the effect of exercise with different intensities on fluoride metabolism in humans, informs sample size planning for any subsequent definitive trial, by providing a robust estimate of the variability of the effect.

  13. Effect of exercise on fluoride metabolism in adult humans: a pilot study

    PubMed Central

    V. Zohoori, Fatemeh; Innerd, Alison; Azevedo, Liane B.; Whitford, Gary M.; Maguire, Anne

    2015-01-01

    An understanding of all aspects of fluoride metabolism is critical to identify its biological effects and avoid fluoride toxicity in humans. Fluoride metabolism and subsequently its body retention may be affected by physiological responses to acute exercise. This pilot study investigated the effect of exercise on plasma fluoride concentration, urinary fluoride excretion and fluoride renal clearance following no exercise and three exercise intensity conditions in nine healthy adults after taking a 1-mg Fluoride tablet. After no, light, moderate and vigorous exercise, respectively, the mean (SD) baseline-adjusted i) plasma fluoride concentration was 9.6(6.3), 11.4(6.3), 15.6(7.7) and 14.9(10.0) ng/ml; ii) rate of urinary fluoride excretion over 0–8 h was 46(15), 44(22), 34(17) and 36(17) μg/h; and iii) rate of fluoride renal clearance was 26.5(9.0), 27.2(30.4), 13.1(20.4) and 18.3(34.9) ml/min. The observed trend of a rise in plasma fluoride concentration and decline in rate of fluoride renal clearance with increasing exercise intensity needs to be investigated in a larger trial. This study, which provides the first data on the effect of exercise with different intensities on fluoride metabolism in humans, informs sample size planning for any subsequent definitive trial, by providing a robust estimate of the variability of the effect. PMID:26581340

  14. Race and Ethnicity, Obesity, Metabolic Health, and Risk of Cardiovascular Disease in Postmenopausal Women

    PubMed Central

    Schmiegelow, Michelle D; Hedlin, Haley; Mackey, Rachel H; Martin, Lisa W; Vitolins, Mara Z; Stefanick, Marcia L; Perez, Marco V; Allison, Matthew; Hlatky, Mark A

    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/m2) as normal weight (body mass index 18.5 to <25), overweight (body mass index 25 to <30), or obese (body mass index ≥30) and by metabolic health, defined first as the metabolic syndrome (metabolically unhealthy: ≥3 metabolic abnormalities) and second as the number of metabolic abnormalities. We used Cox proportional hazards regression to assess associations between baseline characteristics and cardiovascular risk. Over 13 years of follow-up, 1101 women had a first cardiovascular disease event (coronary heart disease or ischemic stroke). Among black women without metabolic syndrome, overweight women had higher adjusted cardiovascular risk than normal weight women (hazard ratio [HR] 1.49), whereas among white women without metabolic syndrome, 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 in black women who were overweight (HR 1.77) or obese (HR 2.17) but not in white women who were overweight (HR 0.98) or obese (HR 1.06). Overweight and obese women with ≤1 metabolic abnormality did not have increased cardiovascular risk, regardless of race or ethnicity. Conclusions Metabolic abnormalities appeared to convey more cardiovascular risk among black women. PMID:25994446

  15. Triad of metabolic syndrome, chronic kidney disease, and coronary heart disease with a focus on microalbuminuria death by overeating.

    PubMed

    Gobal, Freij; Deshmukh, Abhishek; Shah, Sudhir; Mehta, Jawahar L

    2011-06-01

    Coronary heart disease remains a major cause of morbidity and mortality in the United States, and its incidence is rising worldwide. Because atherosclerosis is a chronic process, and it is often associated with certain lifestyle and risk factors such as hypertension, dyslipidemia, and insulin resistance, much emphasis is being placed on lifestyle modification and control of risk factors. It is being recognized that some lifestyle patterns such as overeating result in metabolic syndrome, which may play a role in the development of chronic kidney disease and coronary heart disease. Here, we focus on an important relationship between these 3 conditions, and we provide evidence that microalbuminuria develops in many patients with metabolic syndrome, may be an important correlate of chronic kidney disease and coronary heart disease, and may represent an important prognostic marker. Although the pathogenesis of microalbuminuria in metabolic syndrome is not clear, we suggest that microalbuminuria, chronic kidney disease, and coronary heart disease share common pathways involving inflammation and oxidative stress. We also discuss that a healthy lifestyle is essential for preventing and treating chronic kidney disease and coronary heart disease seen in patients with metabolic syndrome.

  16. Characterization of early host responses in adults with dengue disease

    PubMed Central

    2011-01-01

    Background While dengue-elicited early and transient host responses preceding defervescence could shape the disease outcome and reveal mechanisms of the disease pathogenesis, assessment of these responses are difficult as patients rarely seek healthcare during the first days of benign fever and thus data are lacking. Methods In this study, focusing on early recruitment, we performed whole-blood transcriptional profiling on denguevirus PCR positive patients sampled within 72 h of self-reported fever presentation (average 43 h, SD 18.6 h) and compared the signatures with autologous samples drawn at defervescence and convalescence and to control patients with fever of other etiology. Results In the early dengue fever phase, a strong activation of the innate immune response related genes were seen that was absent at defervescence (4-7 days after fever debut), while at this second sampling genes related to biosynthesis and metabolism dominated. Transcripts relating to the adaptive immune response were over-expressed in the second sampling point with sustained activation at the third sampling. On an individual gene level, significant enrichment of transcripts early in dengue disease were chemokines CCL2 (MCP-1), CCL8 (MCP-2), CXCL10 (IP-10) and CCL3 (MIP-1α), antimicrobial peptide β-defensin 1 (DEFB1), desmosome/intermediate junction component plakoglobin (JUP) and a microRNA which may negatively regulate pro-inflammatory cytokines in dengue infected peripheral blood cells, mIR-147 (NMES1). Conclusions These data show that the early response in patients mimics those previously described in vitro, where early assessment of transcriptional responses has been easily obtained. Several of the early transcripts identified may be affected by or mediate the pathogenesis and deserve further assessment at this timepoint in correlation to severe disease. PMID:21810247

  17. Risk factors for invasive pneumococcal disease among Navajo adults.

    PubMed

    Watt, James P; O'Brien, Katherine L; Benin, Andrea L; McCoy, Sandra I; Donaldson, Connie M; Reid, Raymond; Schuchat, Anne; Zell, Elizabeth R; Hochman, Michael; Santosham, Mathuram; Whitney, Cynthia G

    2007-11-01

    Invasive pneumococcal disease (IPD) is 3-5 times more common among Navajo adults than in the general US population. The authors conducted a case-control study to identify risk factors for IPD among Navajo adults. Navajos aged > or =18 years with IPD were identified through prospective, population-based active laboratory surveillance (December 1999-February 2002). Controls matched to cases on age, gender, and neighborhood were selected. Risk factors were identified through structured interviews and medical record reviews. The authors conducted a matched analysis based on 118 cases and 353 controls. Risk factors included in the final multivariable analysis were chronic renal failure (odds ratio (OR) = 2.6, 95% confidence interval (CI): 0.9, 7.7), congestive heart failure (OR = 5.6, 95% CI: 2.2, 14.5), self-reported alcohol use or alcoholism (OR = 2.9, 95% CI: 1.5, 5.4), body mass index (weight (kg)/height (m)(2)) <5th (OR = 3.2, 95% CI: 1.0, 10.6) or >95th (OR = 2.8, 95% CI: 1.0, 8.0) percentile, and unemployment (OR = 2.6, 95% CI: 1.2, 5.5). The population attributable fractions were 10% for chronic renal failure, 18% for congestive heart failure, 30% for self-reported alcohol use or alcoholism, 6% for body mass index, and 20% for unemployment. Several modifiable risk factors for IPD in Navajos were identified. The high prevalence of renal failure, alcoholism, and unemployment among Navajo adults compared with the general US population may explain some of their increased risk of IPD. PMID:17693393

  18. Metabolic Abnormalities, Cardiovascular Disease Risk Factors, and GFR Decline in Children with Chronic Kidney Disease

    PubMed Central

    Abraham, Alison G.; Jerry-Fluker, Judith; Schwartz, George J.; Benfield, Mark; Kaskel, Frederick; Wong, Craig; Mak, Robert H.; Moxey-Mims, Marva; Warady, Bradley A.

    2011-01-01

    Summary Background and objectives Metabolic abnormalities and cardiovascular disease (CVD) risk factors have rarely been systematically assessed in children with chronic kidney disease (CKD). We examined the prevalence of various CKD sequelae across the GFR spectrum. Design, setting, participants, & measurements Data were used from 586 children participating in the Chronic Kidney Disease in Children (CKiD) study (United States and Canada) with GFR measured by iohexol plasma disappearance. Laboratory values and CVD risk factors were compared across GFR categories and with an age-, gender-, and race-matched community sample. Results CKiD participants were 62% male, 66% Caucasian, 23% African American, and 15% Hispanic with a median age of 11 years and a median GFR of 44 ml/min per 1.73 m2. Compared with those with a GFR ≥ 50 ml/min per 1.73 m2, having a GFR < 30 ml/min per 1.73 m2 was associated with a three-fold higher risk of acidosis and growth failure and a four- to five-fold higher risk of anemia and elevated potassium and phosphate. Median GFR change was −4.3 ml/min per 1.73 m2 and −1.5 ml/min per 1.73 m2 per year in children with glomerular and nonglomerular diagnoses, respectively. Despite medication and access to nephrology care, uncontrolled systolic hypertension was present in 14%, and 16% had left ventricular hypertrophy. Children with CKD frequently were also shorter and had lower birth weight, on average, compared with norms. Conclusions Growth failure, metabolic abnormalities, and CVD risk factors are present at GFR >50 ml/min per 1.73 m2 in children with CKD and, despite therapy, increase in prevalence two- to four-fold with decreasing GFR. PMID:21841064

  19. Prevalence of Eating Disorders in Adults with Celiac Disease

    PubMed Central

    Passananti, V.; Siniscalchi, M.; Zingone, F.; Bucci, C.; Tortora, R.; Iovino, P.; Ciacci, C.

    2013-01-01

    Background. Symptoms of celiac disease negatively impact social activities and emotional state. Aim was to investigate the prevalence of altered eating behaviour in celiac patients. Methods. Celiac patients and controls completed a dietary interview and the Binge Eating Staircases, Eating Disorder Inventory (EDI-2), Eating Attitudes Test, Zung Self-Rating Depression Scale, State Trait Anxiety Inventory Forma Y (STAI-Y1 and STAI-Y2), and Symptom Check List (SCL-90). Results. One hundred celiac adults and 100 controls were not statistically different for gender, age, and physical activity. STAI-Y1 and STAI-Y2, Somatization, Interpersonal, Sensitivity, and Anxiety scores of the SLC-90 were higher in CD patients than controls. EDI-2 was different in pulse thinness, social insecurity, perfectionism, inadequacy, ascetisms, and interpersonal diffidence between CD and HC women, whilst only in interceptive awareness between CD and HC men. A higher EAT-26 score was associated with the CD group dependently with gastrointestinal symptoms. The EAT26 demonstrated association between indices of diet-related disorders in both CD and the feminine gender after controlling for anxiety and depression. Conclusion. CD itself and not gastrointestinal related symptoms or psychological factors may contribute pathological eating behavior in celiac adults. Eating disorders appear to be more frequent in young celiac women than in CD men and in HC. PMID:24369457

  20. Retroperitoneoscopic management of infected cysts in adult polycystic kidney disease.

    PubMed

    Hemal, A K; Gupta, N P; Rajeev, T P; Aron, M; Bhowmik, D; Jain, R

    1999-01-01

    Conservative measures are the mainstay of therapy in adult polycystic kidney disease (APKD). Pain, infection and obstructive uropathy are the major indications for intervention. Chronic pain has been treated with narcotic analgesics, needle aspiration of dominant cysts, and open renal cyst decortication. Laparoscopic cyst decortication, by either transperitoneal or retroperitoneal access, is a new emerging option with similar efficacy to open surgery and less morbidity. Cyst infection in these patients responds poorly to commonly used antibiotics. Patients with refractory cyst infection may even require nephrectomy. Herein, we present 2 cases with APKD that were treated by retroperitoneoscopic decortication for painful and infected cysts. Both patients showed prompt and sustained improvement in symptoms, with minimal morbidity and short convalescence. This approach has not hitherto been described for infected cysts in APKD. The retroperitoneoscopic route should be preferred in the presence of infected cysts so as to prevent intraperitoneal contamination.

  1. Metabolic syndrome: is equine disease comparable to what we know in humans?

    PubMed Central

    Ertelt, Antonia; Barton, Ann-Kristin; Schmitz, Robert R; Gehlen, Heidrun

    2014-01-01

    This review summarizes similarities and differences between the metabolic syndromes in humans and equines, concerning the anatomy, symptoms, and pathophysiological mechanisms. In particular, it discusses the structure and distribution of adipose tissue and its specific metabolic pathways. Furthermore, this article provides insights and focuses on issues concerning laminitis in horses and cardiovascular diseases in humans, as well as their overlap. PMID:24894908

  2. "Design Your Own Disease" Assignment: Teaching Students to Apply Metabolic Pathways

    ERIC Educational Resources Information Center

    Flynn, Nick

    2010-01-01

    One of the major focuses of biochemistry courses is metabolic pathways. Although certain aspects of this content may require a rote approach, more applied techniques make these subject areas more interesting. This article describes the use of an assignment, "Design Your Own Disease" to teach students metabolic regulation and biosignaling…

  3. Metabolic syndrome: is equine disease comparable to what we know in humans?

    PubMed

    Ertelt, Antonia; Barton, Ann-Kristin; Schmitz, Robert R; Gehlen, Heidrun

    2014-09-01

    This review summarizes similarities and differences between the metabolic syndromes in humans and equines, concerning the anatomy, symptoms, and pathophysiological mechanisms. In particular, it discusses the structure and distribution of adipose tissue and its specific metabolic pathways. Furthermore, this article provides insights and focuses on issues concerning laminitis in horses and cardiovascular diseases in humans, as well as their overlap. PMID:24894908

  4. Obesity and Its Cardio-metabolic Co-morbidities Among Adult Nigerians in a Primary Care Clinic of a Tertiary Hospital in South-Eastern, Nigeria

    PubMed Central

    Iloh, Gabriel Uche Pascal; Ikwudinma, Austin Obiora; Obiegbu, Nnadozie Paul

    2013-01-01

    Background: Obesity once thought the medical problem of affluent countries now exist in Nigeria and has been described as a time bomb for the future explosion in the frequency of cardio-metabolic diseases. The most deleterious health consequences of obesity are on the cardiovascular system and associated disorder of lipid and glucose homeostasis. Aim: This study was designed to determine the magnitude of obesity and its cardio-metabolic co-morbidities among adult Nigerians in a primary care clinic of a tertiary hospital South-Eastern, Nigeria. Materials and Methods: A cross-sectional study carried out on 2391 adult Nigerians who were assessed for obesity using body mass index (BMI) criterion. 206 patients who had BMI ≥30kg/m2 were screened for cardio-metabolic co-morbidities. The data collected included basic demographic variables, weight, height, blood pressure; fasting plasma glucose and lipid profile. Results: The prevalence of obesity was 8.6%. Grade I obesity (67.5%) was the most common pattern; others included grade II obesity (23.3%) and grade III obesity (9.2%). Hypertension (42.7%) was the most common cardio-metabolic morbidity. Others included low HDL-cholesterol (22.8%), diabetes mellitus (15.1%), high triglyceride (12.6%), high total cholesterol (9.2%), and high LDL-cholesterol (6.8%). Conclusion: Obesity and its cardio-metabolic morbidities exist among the study population. Anthropometric determination of obesity and screening for its associated cardio-metabolic co-morbidities should constitute clinical targets for intervention in primary care clinics. PMID:24479038

  5. Principles of targeting endothelial cell metabolism to treat angiogenesis and endothelial cell dysfunction in disease

    PubMed Central

    Goveia, Jermaine; Stapor, Peter; Carmeliet, Peter

    2014-01-01

    The endothelium is the orchestral conductor of blood vessel function. Pathological blood vessel formation (a process termed pathological angiogenesis) or the inability of endothelial cells (ECs) to perform their physiological function (a condition known as EC dysfunction) are defining features of various diseases. Therapeutic intervention to inhibit aberrant angiogenesis or ameliorate EC dysfunction could be beneficial in diseases such as cancer and cardiovascular disease, respectively, but current strategies have limited efficacy. Based on recent findings that pathological angiogenesis and EC dysfunction are accompanied by EC-specific metabolic alterations, targeting EC metabolism is emerging as a novel therapeutic strategy. Here, we review recent progress in our understanding of how EC metabolism is altered in disease and discuss potential metabolic targets and strategies to reverse EC dysfunction and inhibit pathological angiogenesis. PMID:25063693

  6. Fetal development and risk of cardiovascular diseases and diabetes type 2 in adult life.

    PubMed

    Szostak-Węgierek, Dorota; Szamotulska, Katarzyna

    2011-01-01

    The fetal origin hypothesis of adult cardiovascular diseases, type 2 diabetes, hypertension and dyslipidemia in persons born with low birthweight, independently of their extrauterine risk factors, has been well established in the last decade of the twentieth century. However, mechanisms responsible for this relationship are still under investigation. Insulin resistance resulting from the restriction of intrauterine development of skeletal muscles and other organs is considered as the most important cause of metabolic disturbances and their cardiovascular complications in adult subjects born with intrauterine growth retardation (IUGR). Decline of insulin secretion, overactivation of the hypothalamo-pituitary-adrenal axis, reduced glucose uptake in the liver and raised lipid oxidation in the muscles may also explain this association. On the other hand, abnormal vascular development , increased activity of the sympathetic nervous system, defective endothelial function and/or impaired renal function in growth restricted newborns may contribute to hypertension in their later life. With respect to maternal conditions and life-style factors that may increase cardiovascular risk in adult offspring born with IUGR, the most consistent results concern pregnancy induced hypertension, preeclampsia, undernutrition, smoking during pregnancy, hypercholesterolemia, inflammation and/or enhanced glucocorticoid secretion. Macrosomia of the newborn, a frequent sequel to maternal diabetes and/or obesity, also increases the risk of diabetes and cardiovascular diseases in adulthood. Maternal overnutrition, and particularly high fat and sugar intake, seem to play a key role in fetal programming of cardiovascular risk in subjects born with macrosomia. Epigenetic imprinting underlies the described pathomechanisms. The presented associations are illustrated, among others, with the results of studies performed by the authors of this review.

  7. Morning and Evening Blue-Enriched Light Exposure Alters Metabolic Function in Normal Weight Adults

    PubMed Central

    Cheung, Ivy N.; Zee, Phyllis C.; Shalman, Dov; Malkani, Roneil G.; Kang, Joseph; Reid, Kathryn J.

    2016-01-01

    Increasing evidence points to associations between light-dark exposure patterns, feeding behavior, and metabolism. This study aimed to determine the acute effects of 3 hours of morning versus evening blue-enriched light exposure compared to dim light on hunger, metabolic function, and physiological arousal. Nineteen healthy adults completed this 4-day inpatient protocol under dim light conditions (<20lux). Participants were randomized to 3 hours of blue-enriched light exposure on Day 3 starting either 0.5 hours after wake (n = 9; morning group) or 10.5 hours after wake (n = 10; evening group). All participants remained in dim light on Day 2 to serve as their baseline. Subjective hunger and sleepiness scales were collected hourly. Blood was sampled at 30-minute intervals for 4 hours in association with the light exposure period for glucose, insulin, cortisol, leptin, and ghrelin. Homeostatic model assessment of insulin resistance (HOMA-IR) and area under the curve (AUC) for insulin, glucose, HOMA-IR and cortisol were calculated. Comparisons relative to baseline were done using t-tests and repeated measures ANOVAs. In both the morning and evening groups, insulin total area, HOMA-IR, and HOMA-IR AUC were increased and subjective sleepiness was reduced with blue-enriched light compared to dim light. The evening group, but not the morning group, had significantly higher glucose peak value during blue-enriched light exposure compared to dim light. There were no other significant differences between the morning or the evening groups in response to blue-enriched light exposure. Blue-enriched light exposure acutely alters glucose metabolism and sleepiness, however the mechanisms behind this relationship and its impacts on hunger and appetite regulation remain unclear. These results provide further support for a role of environmental light exposure in the regulation of metabolism. PMID:27191727

  8. Morning and Evening Blue-Enriched Light Exposure Alters Metabolic Function in Normal Weight Adults.

    PubMed

    Cheung, Ivy N; Zee, Phyllis C; Shalman, Dov; Malkani, Roneil G; Kang, Joseph; Reid, Kathryn J

    2016-01-01

    Increasing evidence points to associations between light-dark exposure patterns, feeding behavior, and metabolism. This study aimed to determine the acute effects of 3 hours of morning versus evening blue-enriched light exposure compared to dim light on hunger, metabolic function, and physiological arousal. Nineteen healthy adults completed this 4-day inpatient protocol under dim light conditions (<20lux). Participants were randomized to 3 hours of blue-enriched light exposure on Day 3 starting either 0.5 hours after wake (n = 9; morning group) or 10.5 hours after wake (n = 10; evening group). All participants remained in dim light on Day 2 to serve as their baseline. Subjective hunger and sleepiness scales were collected hourly. Blood was sampled at 30-minute intervals for 4 hours in association with the light exposure period for glucose, insulin, cortisol, leptin, and ghrelin. Homeostatic model assessment of insulin resistance (HOMA-IR) and area under the curve (AUC) for insulin, glucose, HOMA-IR and cortisol were calculated. Comparisons relative to baseline were done using t-tests and repeated measures ANOVAs. In both the morning and evening groups, insulin total area, HOMA-IR, and HOMA-IR AUC were increased and subjective sleepiness was reduced with blue-enriched light compared to dim light. The evening group, but not the morning group, had significantly higher glucose peak value during blue-enriched light exposure compared to dim light. There were no other significant differences between the morning or the evening groups in response to blue-enriched light exposure. Blue-enriched light exposure acutely alters glucose metabolism and sleepiness, however the mechanisms behind this relationship and its impacts on hunger and appetite regulation remain unclear. These results provide further support for a role of environmental light exposure in the regulation of metabolism. PMID:27191727

  9. Metabolic responses of upper-body accelerometer-controlled video games in adults.

    PubMed

    Stroud, Leah C; Amonette, William E; Dupler, Terry L

    2010-10-01

    Historically, video games required little physical exertion, but new systems utilize handheld accelerometers that require upper-body movement. It is not fully understood if the metabolic workload while playing these games is sufficient to replace routine physical activity. The purpose of this study was to quantify metabolic workloads and estimate caloric expenditure while playing upper-body accelerometer-controlled and classic seated video games. Nineteen adults completed a peak oxygen consumption treadmill test followed by an experimental session where exercising metabolism and ventilation were measured while playing 3 video games: control (CON), low activity (LOW) and high activity (HI). Resting metabolic measures (REST) were also acquired. Caloric expenditure was estimated using the Weir equation. Mean oxygen consumption normalized to body weight for HI condition was greater than LOW, CON, and REST. Mean oxygen consumption normalized to body weight for LOW condition was also greater than CON and REST. Mean exercise intensities of oxygen consumption reserve for HI, LOW, and CON were 25.8% ± 5.1%, 6.4% ± 4.8%, and 0.8% ± 2.4%, respectively. Estimated caloric expenditure during the HI was significantly related to aerobic fitness, but not during other conditions. An active video game significantly elevated oxygen consumption and heart rate, but the increase was dependent on the type of game. The mean oxygen consumption reserve during the HI video game was below recommended international standards for moderate and vigorous activity. Although upper-body accelerometer-controlled video games provided a greater exercising stimulus than classic seated video games, these data suggest they should not replace routine moderate or vigorous exercise.

  10. Metabolic syndrome in hospitalized patients with chronic obstructive pulmonary disease

    PubMed Central

    Slavova, Yanina; Tsakova, Adelina; Genova, Marianka; Kostadinov, Dimitar; Minchev, Delcho; Marinova, Dora

    2015-01-01

    Introduction. The metabolic syndrome (MS) affects 21–53% of patients with chronic obstructive pulmonary disease (COPD) with a higher prevalence in the early stages of COPD, with results being highly variable between studies. MS may also affect natural course of COPD—number of exacerbations, quality of life and lung function. Aim. To examine the prevalence of MS and its correlation with comorbidities and COPD characteristics in patients with COPD admitted for exacerbation. Material and methods. 152 patients with COPD admitted for exacerbation were studied for presence of MS. All of them were also assessed for vitamin D status and diabetes mellitus type 2 (DM). Data were gathered for smoking status and exacerbations during the last year. All patients completed CAT (COPD assessment test) and mMRC (Modified Medical Research Council Dyspnea scale) questionnaires and underwent spirometry. Duration of current hospital stay was recorded. Results. 25% of patients have MS. 23.1% of the male and 29.5% of the female patients have MS (p > 0.05). The prevalence of MS in this study is significantly lower when compared to a national representative study (44.6% in subjects over 45 years). 69.1% of all patients and 97.4% from MS patients have arterial hypertension. The presence of MS is associated with significantly worse cough and sleep (1st and 7th CAT questions; p = 0.002 and p = 0.001 respectively) and higher total CAT score (p = 0.017). Average BMI is 27.31. None of the patients have MS and BMI <25. There is a correlation between the presence of MS and DM (p = 0.008) and with the number of exacerbations in the last year (p = 0.015). There is no correlation between the presence of MS and the pulmonary function. Conclusion. This study among hospitalized COPD patients finds comparable but relatively low prevalence of MS (25%) compared to previously published data (21–53%) and lower prevalence compared to general population (44.6%). MS may impact quality of life and the

  11. Trans-Palmitoleic Acid, Metabolic Risk Factors, and New-Onset Diabetes in US Adults

    PubMed Central

    Mozaffarian, Dariush; Cao, Haiming; King, Irena B.; Lemaitre, Rozenn N.; Song, Xiaoling; Siscovick, David S.; Hotamisligil, Gökhan S.

    2011-01-01

    Background Palmitoleic acid (cis-16:1n-7), produced by endogenous fat synthesis, has been linked to both beneficial and deleterious metabolic effects, potentially confounded by diverse determinants and tissue sources of endogenous production. Trans-palmitoleate (trans-16:1n-7) represents a distinctly exogenous source of 16:1n-7, unconfounded by endogenous synthesis or its determinants, that may be uniquely informative. Objective We investigated whether circulating trans-palmitoleate was independently related to lower metabolic risk and incident type2 diabetes. Design Prospective cohort study (1992–2006). Setting Four US communities. Patients 3,736 adults in the Cardiovascular Health Study. Measurements Plasma phospholipid fatty acids, anthropometry, blood lipids, inflammatory markers, and glucose-insulin levels were measured at baseline in 1992; and diet, 3 years earlier. In multivariable-adjusted models, we investigated how demographic, clinical, and lifestyle factors independently related to trans-palmitoleate; how trans-palmitoleate related to major metabolic risk factors; and how trans-palmitoleate related to new-onset diabetes (304 incident cases). We validated findings for metabolic risk factors in an independent cohort of 327 women. Results In multivariable-analyses, whole-fat dairy consumption was most strongly associated with higher trans-palmitoleate. Higher trans-palmitoleate was associated with slightly lower adiposity and, independently, higher high-density-lipoprotein(HDL)-cholesterol (across quintiles: +1.9%, P=0.04), lower triglycerides (−19.0%, P<0.001), lower total:HDL-cholesterol (−4.7%, P<0.001), lower C-reactive protein (−13.8%, P=0.05), and lower insulin resistance (−16.7%, P<0.001). Trans-palmitoleate was associated with substantially lower incidence of diabetes, with multivariable-hazard-ratios=0.41 (95%CI=0.27–0.64) and 0.38 (95%CI=0.24–0.62) in quintile-4 and quintile-5, versus quintile-1 (P-trend<0.001). Findings were

  12. Clinical biochemistry of the neonatal period: immaturity, hypoxia, and metabolic disease.

    PubMed Central

    Harkness, R A

    1987-01-01

    This review attempts to provide practical information on common problems in the laboratory medicine of newborn infants and also considers unresolved problems in achieving neonatal diagnoses. A common cause of upset in the newborn--intrapartum asphyxia--can now be positively diagnosed. This leaves a small group whom it is necessary to investigate because they may have metabolic disease. The initial investigation of metabolic disease at the district general hospital should be limited to the commoner conditions. PMID:3312303

  13. Recent developments on the role of epigenetics in obesity and metabolic disease.

    PubMed

    van Dijk, Susan J; Tellam, Ross L; Morrison, Janna L; Muhlhausler, Beverly S; Molloy, Peter L

    2015-01-01

    The increased prevalence of obesity and related comorbidities is a major public health problem. While genetic factors undoubtedly play a role in determining individual susceptibility to weight gain and obesity, the identified genetic variants only explain part of the variation. This has led to growing interest in understanding the potential role of epigenetics as a mediator of gene-environment interactions underlying the development of obesity and its associated comorbidities. Initial evidence in support of a role of epigenetics in obesity and type 2 diabetes mellitus (T2DM) was mainly provided by animal studies, which reported epigenetic changes in key metabolically important tissues following high-fat feeding and epigenetic differences between lean and obese animals and by human studies which showed epigenetic changes in obesity and T2DM candidate genes in obese/diabetic individuals. More recently, advances in epigenetic methodologies and the reduced cost of epigenome-wide association studies (EWAS) have led to a rapid expansion of studies in human populations. These studies have also reported epigenetic differences between obese/T2DM adults and healthy controls and epigenetic changes in association with nutritional, weight loss, and exercise interventions. There is also increasing evidence from both human and animal studies that the relationship between perinatal nutritional exposures and later risk of obesity and T2DM may be mediated by epigenetic changes in the offspring. The aim of this review is to summarize the most recent developments in this rapidly moving field, with a particular focus on human EWAS and studies investigating the impact of nutritional and lifestyle factors (both pre- and postnatal) on the epigenome and their relationship to metabolic health outcomes. The difficulties in distinguishing consequence from causality in these studies and the critical role of animal models for testing causal relationships and providing insight into underlying

  14. Relationships Between Metabolic Rate, Muscle Electromyograms and Swim Performance of Adult Chinook Salmon

    SciTech Connect

    Geist, David R.; Brown, Richard S.; Cullinan, Valerie I.; Mesa, Matthew G.; VanderKooi, S P.; McKinstry, Craig A.

    2003-10-01

    In 2000 Pacific Northwest National Laboratory initiated a two-year study to investigate the metabolic rate and swimming performance and to estimate the total energy used (i.e., aerobic and anaerobic) by adult spring Chinook salmon migrating upstream through a large hydropower dam on the Columbia River. The investigation involved one year of laboratory study and one year of field study at Bonneville Dam. The objectives of the laboratory study, reported here, were to (1) measure active rates of oxygen consumption of adult spring chinook salmon at three water temperatures over a range of swimming speeds; (2) estimate the Ucrit of adult spring chinook salmon; and (3) monitor EMGs of red and white muscle in the salmon over a range of swimming speeds. Future papers will report on the results of the field study. Our results indicated that the rate of oxygen consumption and red and white muscle activity in adult spring chinook salmon were strongly correlated with swimming speed over a range of fish sizes and at three different temperatures. Active oxygen consumption increased linearly with swim speed before leveling off at speeds at or above Ucrit. This pattern was similar at each water temperature and indicated that fish were approaching their maximal aerobic oxygen consumption at higher swim speeds. Modeling showed that temperature, but not size or sex, influenced the relation between V02 and swim speed, thus a V02-swim speed model based on temperature (but independent of sex and size) should be a biologically relevant way of estimating the energy use of fish in the wild.

  15. Pediatric non alcoholic fatty liver disease: old and new concepts on development, progression, metabolic insight and potential treatment targets

    PubMed Central

    2013-01-01

    Nonalcoholic fatty liver disease (NAFLD) is the leading cause of chronic liver disease in children. NAFLD has emerged to be extremely prevalent, and predicted by obesity and male gender. It is defined by hepatic fat infiltration >5% hepatocytes, in the absence of other causes of liver pathology. It includes a spectrum of disease ranging from intrahepatic fat accumulation (steatosis) to various degrees of necrotic inflammation and fibrosis (non-alcoholic steatohepatatis [NASH]). NAFLD is associated, in children as in adults, with severe metabolic impairments, determining an increased risk of developing the metabolic syndrome. It can evolve to cirrhosis and hepatocellular carcinoma, with the consequent need for liver transplantation. Both genetic and environmental factors seem to be involved in the development and progression of the disease, but its physiopathology is not yet entirely clear. In view of this mounting epidemic phenomenon involving the youth, the study of NAFLD should be a priority for all health care systems. This review provides an overview of current and new clinical-histological concepts of pediatric NAFLD, going through possible implications into patho-physiolocical and therapeutic perspectives. PMID:23530957

  16. Perinatal Exposure of Mice to the Pesticide DDT Impairs Energy Expenditure and Metabolism in Adult Female Offspring

    PubMed Central

    La Merrill, Michele; Karey, Emma; Moshier, Erin; Lindtner, Claudia; La Frano, Michael R.; Newman, John W.; Buettner, Christoph

    2014-01-01

    Dichlorodiphenyltrichloroethane (DDT) has been used extensively to control malaria, typhus, body lice and bubonic plague worldwide, until countries began restricting its use in the 1970s. Its use in malaria control continues in some countries according to recommendation by the World Health Organization. Individuals exposed to elevated levels of DDT and its metabolite dichlorodiphenyldichloroethylene (DDE) have an increased prevalence of diabetes and insulin resistance. Here we hypothesize that perinatal exposure to DDT disrupts metabolic programming leading to impaired metabolism in adult offspring. To test this, we administered DDT to C57BL/6J mice from gestational day 11.5 to postnatal day 5 and studied their metabolic phenotype at several ages up to nine months. Perinatal DDT exposure reduced core body temperature, impaired cold tolerance, decreased energy expenditure, and produced a transient early-life increase in body fat in female offspring. When challenged with a high fat diet for 12 weeks in adulthood, female offspring perinatally exposed to DDT developed glucose intolerance, hyperinsulinemia, dyslipidemia, and altered bile acid metabolism. Perinatal DDT exposure combined with high fat feeding in adulthood further impaired thermogenesis as evidenced by reductions in core temperature and in the expression of numerous RNA that promote thermogenesis and substrate utilization in the brown adipose tissue of adult female mice. These observations suggest that perinatal DDT exposure impairs thermogenesis and the metabolism of carbohydrates and lipids which may increase susceptibility to the metabolic syndrome in adult female offspring. PMID:25076055

  17. Selected dietary nutrients and the prevalence of metabolic syndrome in adult males and females in Saudi Arabia: a pilot study.

    PubMed

    Al-Daghri, Nasser M; Khan, Nasiruddin; Alkharfy, Khalid M; Al-Attas, Omar S; Alokail, Majed S; Alfawaz, Hanan A; Alothman, Abdulaziz; Vanhoutte, Paul M

    2013-11-01

    During the last decade, the rapid economic development in Saudi Arabia resulted in an unbalanced dietary intake pattern within the general population. Consequently, metabolic syndrome was also documented to be highly prevalent in the Middle-East region. We aimed to examine the relationship between selected dietary nutrient intakes and the prevalence of metabolic syndrome in the general adult population of Riyadh, Saudi Arabia. In this cross-sectional study, 185 adult Saudis aged 19 to 60 years (87 males and 98 females (mean age 35.6 ± 13.2 and 37.6 ± 11.7 years, respectively)) were included. The criteria for metabolic syndrome were based on the International Diabetes Foundation (IDF) criteria, and the dietary food intake was assessed by two 24-h dietary recall methods. The odd ratios (ORs) of metabolic syndrome risk across quartiles of selected dietary nutrients were significantly lower for carbohydrates and proteins, as well as for vitamins A, C, E and K, calcium, zinc and magnesium (p < 0.05 for all) in the female group with metabolic syndrome than those without. The pattern of daily dietary intake of selected nutrients among the general population of Saudi Arabia raises concern, and this dietary imbalance could increase the risk of metabolic syndrome, particularly in adult Saudi females.

  18. Perinatal exposure of mice to the pesticide DDT impairs energy expenditure and metabolism in adult female offspring.

    PubMed

    La Merrill, Michele; Karey, Emma; Moshier, Erin; Lindtner, Claudia; La Frano, Michael R; Newman, John W; Buettner, Christoph

    2014-01-01

    Dichlorodiphenyltrichloroethane (DDT) has been used extensively to control malaria, typhus, body lice and bubonic plague worldwide, until countries began restricting its use in the 1970s. Its use in malaria control continues in some countries according to recommendation by the World Health Organization. Individuals exposed to elevated levels of DDT and its metabolite dichlorodiphenyldichloroethylene (DDE) have an increased prevalence of diabetes and insulin resistance. Here we hypothesize that perinatal exposure to DDT disrupts metabolic programming leading to impaired metabolism in adult offspring. To test this, we administered DDT to C57BL/6J mice from gestational day 11.5 to postnatal day 5 and studied their metabolic phenotype at several ages up to nine months. Perinatal DDT exposure reduced core body temperature, impaired cold tolerance, decreased energy expenditure, and produced a transient early-life increase in body fat in female offspring. When challenged with a high fat diet for 12 weeks in adulthood, female offspring perinatally exposed to DDT developed glucose intolerance, hyperinsulinemia, dyslipidemia, and altered bile acid metabolism. Perinatal DDT exposure combined with high fat feeding in adulthood further impaired thermogenesis as evidenced by reductions in core temperature and in the expression of numerous RNA that promote thermogenesis and substrate utilization in the brown adipose tissue of adult female mice. These observations suggest that perinatal DDT exposure impairs thermogenesis and the metabolism of carbohydrates and lipids which may increase susceptibility to the metabolic syndrome in adult female offspring.

  19. Updates in vaccination: Recommendations for adult inflammatory bowel disease patients

    PubMed Central

    Chaudrey, Khadija; Salvaggio, Michelle; Ahmed, Aftab; Mahmood, Sultan; Ali, Tauseef

    2015-01-01

    Treatment regimens for inflammatory bowel disease (IBD) incorporate the use of a variety of immunosuppressive agents that increase the risk of infections. Prevention of many of these infections can be achieved by the timely and judicious use of vaccinations. IBD patients tend to be under-immunized. Some of the contributing factors are lack of awareness regarding the significance of vaccinating IBD patients, misperception about safety of vaccinations in immunocompromised patients, ambiguity about the perceived role of the gastroenterologist in contrast to the primary care physician and unavailability of vaccination guidelines focused on IBD population. In general, immunocompetent IBD patients can be vaccinated using standard vaccination recommendations. However there are special considerations for IBD patients receiving immunosuppressive therapy, IBD travelers and pregnant women with IBD. This review discusses current vaccination recommendations with updates for adult IBD patients. Centers for Disease Control and Prevention 2013 vaccination guidelines with 2014 updates and the Advisory Committee on Immunization Practices recommendations have been highlighted as a primary source of recommendations. PMID:25805924

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