WorldWideScience

Sample records for good metabolic control

  1. Diabetes in children and adolescents from ethnic minorities: barriers to education, treatment and good metabolic control

    DEFF Research Database (Denmark)

    Povlsen, Lene; Olsen, Birthe; Ladelund, Steen

    2005-01-01

    AIM: This paper reports an investigation to establish whether metabolic control is different in children and adolescents from ethnic minorities with type 1 diabetes compared with young Danish patients, and to learn about factors affecting their opportunities to achieve good metabolic control....... BACKGROUND: The prevalence of diabetes in children and adolescents from ethnic minorities in Denmark is increasing. Having a different ethnic background has frequently been described as a risk factor for poor metabolic control, but whether the risk is represented by the ethnicity and immigration itself...... the centres provided limited specialized knowledge and support. The questionnaires completed by the parents revealed limited schooling, lack of professional education and a major need for interpreters; these characteristics were especially prevalent among the mothers. CONCLUSIONS: Young patients from ethnic...

  2. Customs control of goods

    Directory of Open Access Journals (Sweden)

    Mentor Gashi

    2015-11-01

    Full Text Available Customs control, is regulated by law in different countries. Different countries define through the law, the control of goods.. Main purpose of this paper is to analyze two types of customs controls, and their effect in reducing avoidance of duty or tax evasion which may be caused by the import of goods of certain companies. For this reason we researched which model is implemented in developing countries and what results were reached through questionnaires. In this sense the next research question, consists in defining the moment of customs control pre or post-clearance control of goods.

  3. Subjective-Objective Sleep Discrepancy Is Associated With Alterations in Regional Glucose Metabolism in Patients With Insomnia and Good Sleeper Controls.

    Science.gov (United States)

    Kay, Daniel B; Karim, Helmet T; Soehner, Adriane M; Hasler, Brant P; James, Jeffrey A; Germain, Anne; Hall, Martica H; Franzen, Peter L; Price, Julie C; Nofzinger, Eric A; Buysse, Daniel J

    2017-11-01

    Sleep discrepancies are common in primary insomnia (PI) and include reports of longer sleep onset latency (SOL) than measured by polysomnography (PSG) or "negative SOL discrepancy." We hypothesized that negative SOL discrepancy in PI would be associated with higher relative glucose metabolism during nonrapid eye movement (NREM) sleep in brain networks involved in conscious awareness, including the salience, left executive control, and default mode networks. PI (n = 32) and good sleeper controls (GS; n = 30) completed [18F]fluorodeoxyglucose positron emission tomography (FDG-PET) scans during NREM sleep, and relative regional cerebral metabolic rate for glucose (rCMRglc) was measured. Sleep discrepancy was calculated by subtracting PSG-measured SOL on the PET night from corresponding self-report values the following morning. We tested for interactions between group (PI vs. GS) and SOL discrepancy for rCMRglc during NREM sleep using both a region of interest mask and exploratory whole-brain analyses. Significant group by SOL discrepancy interactions for rCMRglc were observed in several brain regions (pcorrected PSG-measured SOL) was associated with significantly higher relative rCMRglc in the right anterior insula and middle/posterior cingulate during NREM sleep. In GS, more positive SOL discrepancy (self-reported Sleep Research Society 2017. Published by Oxford University Press on behalf of the Sleep Research Society. All rights reserved. For permissions, please e-mail journals.permissions@oup.com.

  4. Lack of association of colonic epithelium telomere length and oxidative DNA damage in Type 2 diabetes under good metabolic control

    Directory of Open Access Journals (Sweden)

    Kennedy Hugh

    2008-10-01

    Full Text Available Abstract Background Telomeres are DNA repeat sequences necessary for DNA replication which shorten at cell division at a rate directly related to levels of oxidative stress. Critical telomere shortening predisposes to cell senescence and to epithelial malignancies. Type 2 diabetes is characterised by increased oxidative DNA damage, telomere attrition, and an increased risk of colonic malignancy. We hypothesised that the colonic mucosa in Type 2 diabetes would be characterised by increased DNA damage and telomere shortening. Methods We examined telomere length (by flow fluorescent in situ hybridization and oxidative DNA damage (flow cytometry of 8 – oxoguanosine in the colonic mucosal cells of subjects with type 2 diabetes (n = 10; mean age 62.2 years, mean HbA1c 6.9% and 22 matched control subjects. No colonic pathology was apparent in these subjects at routine gastrointestinal investigations. Results Mean colonic epithelial telomere length in the diabetes group was not significantly different from controls (10.6 [3.6] vs. 12.1 [3.4] Molecular Equivalent of Soluble Fluorochrome Units [MESF]; P = 0.5. Levels of oxidative DNA damage were similar in both T2DM and control groups (2.6 [0.6] vs. 2.5 [0.6] Mean Fluorescent Intensity [MFI]; P = 0.7. There was no significant relationship between oxidative DNA damage and telomere length in either group (both p > 0.1. Conclusion Colonic epithelium in Type 2 diabetes does not differ significantly from control colonic epithelium in oxidative DNA damage or telomere length. There is no evidence in this study for increased oxidative DNA damage or significant telomere attrition in colonic mucosa as a carcinogenic mechanism.

  5. Engineering of metabolic control

    Science.gov (United States)

    Liao, James C.

    2004-03-16

    The invention features a method of producing heterologous molecules in cells under the regulatory control of a metabolite and metabolic flux. The method can enhance the synthesis of heterologous polypeptides and metabolites.

  6. Why Quorum Sensing Controls Private Goods

    Directory of Open Access Journals (Sweden)

    Martin Schuster

    2017-05-01

    Full Text Available Cell-cell communication, also termed quorum sensing (QS, is a widespread process that coordinates gene expression in bacterial populations. The generally accepted view is that QS optimizes the cell density-dependent benefit attained from cooperative behaviors, often in the form of secreted products referred to as “public goods.” This view is challenged by an increasing number of cell-associated products or “private goods” reported to be under QS-control for which a collective benefit is not apparent. A prominent example is nucleoside hydrolase from Pseudomonas aeruginosa, a periplasmic enzyme that catabolizes adenosine. Several recent studies have shown that private goods can function to stabilize cooperation by co-regulated public goods, seemingly explaining their control by QS. Here we argue that this property is a by-product of selection for other benefits rather than an adaptation. Emphasizing ecophysiological context, we propose alternative explanations for the QS control of private goods. We suggest that the benefit attained from private goods is associated with high cell density, either because a relevant ecological condition correlates with density, or because the private good is, directly or indirectly, involved in cooperative behavior. Our analysis helps guide a systems approach to QS, with implications for antivirulence drug design and synthetic biology.

  7. Internal Control Good Cooperative Governance And Performance

    Directory of Open Access Journals (Sweden)

    Andry Arifian Rachman

    2017-11-01

    Full Text Available This study aims to examine the influence of internal control and good cooperative governance partially and simultaneously to the performance of cooperatives in West Java Province. The research method used in this research is descriptive and verification. The sample in this research is 22 boards as manager of cooperative in West Java Province. The data used in the research is the primary data through questionnaire collection. Validity and reliability testing is performed before hypothesis testing. This research uses multiple regression analysis technique. Based on hypothesis testing obtained 1 internal control has no significant effect on performance 2 good cooperative governance has a significant effect on performance and 3 internal control and good cooperative governance have a significant effect on performance.

  8. Topological analysis of metabolic control.

    Science.gov (United States)

    Sen, A K

    1990-12-01

    A topological approach is presented for the analysis of control and regulation in metabolic pathways. In this approach, the control structure of a metabolic pathway is represented by a weighted directed graph. From an inspection of the topology of the graph, the control coefficients of the enzymes are evaluated in a heuristic manner in terms of the enzyme elasticities. The major advantage of the topological approach is that it provides a visual framework for (1) calculating the control coefficients of the enzymes, (2) analyzing the cause-effect relationships of the individual enzymes, (3) assessing the relative importance of the enzymes in metabolic regulation, and (4) simplifying the structure of a given pathway, from a regulatory viewpoint. Results are obtained for (a) an unbranched pathway in the absence of feedback the feedforward regulation and (b) an unbranched pathway with feedback inhibition. Our formulation is based on the metabolic control theory of Kacser and Burns (1973) and Heinrich and Rapoport (1974).

  9. WHOLESALER TO RETAILER GOODS FORWARDING CONTROLLING

    Directory of Open Access Journals (Sweden)

    Oleg NIKIFOROV

    2016-06-01

    Full Text Available The modern trends in the development of logistics controlling through the prism of collaboration between wholesale companies and retail chains have been considered. The nature and structure of cargo transportation by the wholesale company to the retail chain have been analysed. The key transportation processes have been identified and the reliance on transportation drivers-forwarders for their effectiveness has been determined. The study has resulted in the program-mathematical approach to the transportation controlling automation used by the wholesale company to deliver goods to the retail chain as well as the mathematical model of the system information flow. The practical recommendations for the mathematical software implementation using the AWS Forwarder software product as an example have been illustrated.

  10. Three good reasons for heart surgeons to understand cardiac metabolism.

    Science.gov (United States)

    Doenst, Torsten; Bugger, Heiko; Schwarzer, Michael; Faerber, Gloria; Borger, Michael A; Mohr, Friedrich W

    2008-05-01

    It is the principal goal of cardiac surgeons to improve or reinstate contractile function with, through or after a surgical procedure on the heart. Uninterrupted contractile function of the heart is irrevocably linked to the uninterrupted supply of energy in the form of ATP. Thus, it would appear natural that clinicians interested in myocardial contractile function are interested in the way the heart generates ATP, i.e. the processes generally referred to as energy metabolism. Yet, it may appear that the relevance of energy metabolism in cardiac surgery is limited to the area of cardioplegia, which is a declining research interest. It is the goal of this review to change this trend and to illustrate the role and the therapeutic potential of metabolism and metabolic interventions for management. We present three compelling reasons why cardiac metabolism is of direct, practical interest to the cardiac surgeon and why a better understanding of energy metabolism might indeed result in improved surgical outcomes: (1) To understand cardioplegic arrest, ischemia and reperfusion, one needs a working knowledge of metabolism; (2) hyperglycemia is an underestimated and modifiable risk factor; (3) acute metabolic interventions can be effective in patients undergoing cardiac surgery.

  11. Control Is Good, But Trust Is Cheaper

    DEFF Research Database (Denmark)

    Jensen, Keld; Svendsen, Gert Tinggaard

    2014-01-01

    -detailed contracts, all to the end of tightening control. Control over employees, control over clients and customers, control over business processes and outcomes. But with what results? Does Lenin’s little management maxim work out well in practice? Or have managements overestimated and overemphasized control......’s virtues, to the detriment of productivity, profits and even social progress?...

  12. Compliance or good control and accountability

    International Nuclear Information System (INIS)

    Erkkila, B.H.

    1993-01-01

    DOE Orders and draft orders for nuclear material control and accountability address the need for a complete material control and accountability (MC ampersand A) program for all DOE contractors processing, using, and/or storing nuclear materials. These orders also address performance as well as compliance issues. Very often the existence of a program or an element of a program satisfies the compliance aspect of DOE requirements. The concept of performance requirements is new and requires new thinking with all of the elements of the MC ampersand A program. The contractor is so accustomed to compliance with DOE requirements that dealing with performance is not well understood. In this paper I will address the receptiveness of performance requirements by the contractor. Auditing for performance is also a new concept and has not been implemented. The contractor will have to learn how to measure the performance of the MC ampersand A program and be able to demonstrate a certain level of performance to the oversight organization. This paper will contain a discussion of a well organized MC ampersand A program, the compliance issues associated with the program, the performance criteria associated with the program, and how to audit such a program

  13. INTERNAL CONTROLS IN ENSURING GOOD CORPORATE GOVERNANCE IN FINANCIAL INSTITUTIONS

    Directory of Open Access Journals (Sweden)

    KOSMAS NJANIKE

    2011-01-01

    Full Text Available This paper assessed factors that influence the internal controls in ensuring good corporate governance in financial institutions in developing economies with special reference to Zimbabwe. The research paper assessed how lack of internal controls affected good corporate governance and aimed to bring out elements of good corporate governance. It emerged that failure to effectively implement internal controls contributed significantly to poor corporate governance. The study discovered that internal control system overrides and the issue of “fact cat” directors also contributed to poor corporate governance. The study recommended that there is need for the board of directors to guarantee an organizational structure that clearly defines management responsibilities, authority and reporting relationships. There is also need to ensure that delegated responsibilities are effectively carried out to ensure compliance with internal controls of the financial institution concerned.

  14. TORCing up metabolic control in the brain.

    Science.gov (United States)

    Hietakangas, Ville; Cohen, Stephen M

    2008-05-01

    Transducer of regulated CREB activity 2 (TORC2) is a coactivator of CREB and an important regulator of energy balance in mammals through control of gluconeogenesis in the liver. In this issue of Cell Metabolism, Wang and coworkers (2008) report an intriguing role for Drosophila TORC in the neuronal regulation of metabolism.

  15. Control of fluxes in metabolic networks

    Science.gov (United States)

    Basler, Georg; Nikoloski, Zoran; Larhlimi, Abdelhalim; Barabási, Albert-László; Liu, Yang-Yu

    2016-01-01

    Understanding the control of large-scale metabolic networks is central to biology and medicine. However, existing approaches either require specifying a cellular objective or can only be used for small networks. We introduce new coupling types describing the relations between reaction activities, and develop an efficient computational framework, which does not require any cellular objective for systematic studies of large-scale metabolism. We identify the driver reactions facilitating control of 23 metabolic networks from all kingdoms of life. We find that unicellular organisms require a smaller degree of control than multicellular organisms. Driver reactions are under complex cellular regulation in Escherichia coli, indicating their preeminent role in facilitating cellular control. In human cancer cells, driver reactions play pivotal roles in malignancy and represent potential therapeutic targets. The developed framework helps us gain insights into regulatory principles of diseases and facilitates design of engineering strategies at the interface of gene regulation, signaling, and metabolism. PMID:27197218

  16. Thermodynamics of the control of metabolism

    NARCIS (Netherlands)

    Westerhoff, H. V.; Plomp, P. J.; Groen, A. K.; Wanders, R. J.

    1987-01-01

    A theory is presented, describing the control analysis of metabolic systems in terms of Gibbs free energies, extending earlier work of Kacser and Burns (25), and Heinrich and Rapoport (29). It is shown that relationships exist between flux control coefficients (the degree to which enzymes control

  17. The Microbiological Memory, an Epigenetic Regulator Governing the Balance Between Good Health and Metabolic Disorders

    Directory of Open Access Journals (Sweden)

    Christian A. Devaux

    2018-06-01

    Full Text Available If the transmission of biological information from one generation to the next is based on DNA, most heritable phenotypic traits such as chronic metabolic diseases, are not linked to genetic variation in DNA sequences. Non-genetic heritability might have several causes including epigenetic, parental effect, adaptive social learning, and influence of the ecological environment. Distinguishing among these causes is crucial to resolve major phenotypic enigmas. Strong evidence indicates that changes in DNA expression through various epigenetic mechanisms can be linked to parent-offspring resemblance in terms of sensitivity to metabolic diseases. Among non-genetic heritable traits, early nutrition could account for a long term deviant programming of genes expression responsible for metabolic diseases in adulthood. Nutrition could shape an inadequate gut microbiota (dysbiosis, triggering epigenetic deregulation of transcription which can be observed in chronic metabolic diseases. We review herein the evidence that dysbiosis might be a major cause of heritable epigenetic patterns found to be associated with metabolic diseases. By taking into account the recent advances on the gut microbiome, we have aggregated together different observations supporting the hypothesis that the gut microbiota could promote the molecular crosstalk between bacteria and surrounding host cells which controls the pathological epigenetic signature. We introduce for the first time the concept of “microbiological memory” as the main regulator of the epigenetic signatures, thereby indicating that different causes of non-genetic heritability can interact in complex pathways to produce inheritance.

  18. Radiopharmaceuticals good practices handbook: ARCAL XV radiopharmaceuticals control and production

    International Nuclear Information System (INIS)

    Verdera Presto, Silvia

    1998-01-01

    A safety practice of the therapeutics diagnostic proceeding in nuclear medicine require a permanent provide high quality radiopharmaceuticals manufacture. This work treat to give a guide for all radio pharmacies laboratories that produce,control, fraction and or dispense radiopharmaceuticals products, with attention hospitable radiopharmacy laboratory. Three chapters with recommendations in manufacture good practice in Hospital radiopharmacy, industrial centralized, bibliography and three annexe's about clean area classification,standards work in laminar flux bell, and guarantee and cleaning areas

  19. Availability of public goods shapes the evolution of competing metabolic strategies.

    Science.gov (United States)

    Bachmann, Herwig; Fischlechner, Martin; Rabbers, Iraes; Barfa, Nakul; Branco dos Santos, Filipe; Molenaar, Douwe; Teusink, Bas

    2013-08-27

    Tradeoffs provide a rationale for the outcome of natural selection. A prominent example is the negative correlation between the growth rate and the biomass yield in unicellular organisms. This tradeoff leads to a dilemma, where the optimization of growth rate is advantageous for an individual, whereas the optimization of the biomass yield would be advantageous for a population. High-rate strategies are observed in a broad variety of organisms such as Escherichia coli, yeast, and cancer cells. Growth in suspension cultures favors fast-growing organisms, whereas spatial structure is of importance for the evolution of high-yield strategies. Despite this realization, experimental methods to directly select for increased yield are lacking. We here show that the serial propagation of a microbial population in a water-in-oil emulsion allows selection of strains with increased biomass yield. The propagation in emulsion creates a spatially structured environment where the growth-limiting substrate is privatized for populations founded by individual cells. Experimental evolution of several isogenic Lactococcus lactis strains demonstrated the existence of a tradeoff between growth rate and biomass yield as an apparent Pareto front. The underlying mutations altered glucose transport and led to major shifts between homofermentative and heterofermentative metabolism, accounting for the changes in metabolic efficiency. The results demonstrated the impact of privatizing a public good on the evolutionary outcome between competing metabolic strategies. The presented approach allows the investigation of fundamental questions in biology such as the evolution of cooperation, cell-cell interactions, and the relationships between environmental and metabolic constraints.

  20. Strengthening the regulatory control of consumer goods through international harmonization

    International Nuclear Information System (INIS)

    Yus Rusdian Akhmad

    2013-01-01

    The International Atomic Energy Agency (IAEA) is currently working on a recommendation in the form of guidelines for regulating consumer goods. Preparation of this document has a significant dimension of international issues, especially in terms of the application of the principles of justification and application of the concept of exemption. International harmonization among regulators ranging from the regional to the global level is a central issue and considering the complex issues that arise in addition to covering the scientific aspects also involve consideration of the legal aspects or values espoused by any State which may differ from one another. PERKA BAPETEN on consumer goods is still in the preparation stage so that the discussion of the material will be useful for improving the quality of the regulation in time. There is a significant gap of understanding to the related materials by the parties concerned (between local and international parties were among the local party). This paper intends to propose the understanding and views on radiation protection and regulatory control for consumer goods and hopely could contributed significantly to strengthening its regulatory control which is primarily through a reduction in the gap of understanding to the related concept that potentially multi perceptions and encourage stronger cooperation among regulatory bodies. (author)

  1. Asymmetric public goods game cooperation through pest control.

    Science.gov (United States)

    Reeves, T; Ohtsuki, H; Fukui, S

    2017-12-21

    Cooperation in a public goods game has been studied extensively to find the conditions for sustaining the commons, yet the effect of asymmetry between agents has been explored very little. Here we study a game theoretic model of cooperation for pest control among farmers. In our simple model, each farmer has a paddy of the same size arranged adjacently on a line. A pest outbreak occurs at an abandoned paddy at one end of the line, directly threatening the frontier farmer adjacent to it. Each farmer pays a cost of his or her choice to an agricultural collective, and the total sum held by the collective is used for pest control, with success probability increasing with the sum. Because the farmers' incentives depend on their distance from the pest outbreak, our model is an asymmetric public goods game. We derive each farmer's cost strategy at the Nash equilibrium. We find that asymmetry among farmers leads to a few unexpected outcomes. The individual costs at the equilibrium do not necessarily increase with how much the future is valued but rather show threshold behavior. Moreover, an increase in the number of farmers can sometimes paradoxically undermine pest prevention. A comparison with a symmetric public goods game model reveals that the farmer at the greatest risk pays a disproportionate amount of cost in the asymmetric game, making the use of agricultural lands less sustainable. Copyright © 2017 The Authors. Published by Elsevier Ltd.. All rights reserved.

  2. Metabolic gene polymorphism frequencies in control populations

    DEFF Research Database (Denmark)

    Garte, Seymour; Gaspari, Laura; Alexandrie, Anna-Karin

    2001-01-01

    Using the International Project on Genetic Susceptibility to Environmental Carcinogens (GSEC) database containing information on over 15,000 control (noncancer) subjects, the allele and genotype frequencies for many of the more commonly studied metabolic genes (CYP1A1, CYP2E1, CYP2D6, GSTM1, GSTT1...

  3. Good laboratory practices for biochemical genetic testing and newborn screening for inherited metabolic disorders.

    Science.gov (United States)

    2012-04-06

    Biochemical genetic testing and newborn screening are essential laboratory services for the screening, detection, diagnosis, and monitoring of inborn errors of metabolism or inherited metabolic disorders. Under the Clinical Laboratory Improvement Amendments of 1988 (CLIA) regulations, laboratory testing is categorized on the basis of the level of testing complexity as either waived (i.e., from routine regulatory oversight) or nonwaived testing (which includes tests of moderate and high complexity). Laboratories that perform biochemical genetic testing are required by CLIA regulations to meet the general quality systems requirements for nonwaived testing and the personnel requirements for high-complexity testing. Laboratories that perform public health newborn screening are subject to the same CLIA regulations and applicable state requirements. As the number of inherited metabolic diseases that are included in state-based newborn screening programs continues to increase, ensuring the quality of performance and delivery of testing services remains a continuous challenge not only for public health laboratories and other newborn screening facilities but also for biochemical genetic testing laboratories. To help ensure the quality of laboratory testing, CDC collaborated with the Centers for Medicare & Medicaid Services, the Food and Drug Administration, the Health Resources and Services Administration, and the National Institutes of Health to develop guidelines for laboratories to meet CLIA requirements and apply additional quality assurance measures for these areas of genetic testing. This report provides recommendations for good laboratory practices that were developed based on recommendations from the Clinical Laboratory Improvement Advisory Committee, with additional input from the Secretary's Advisory Committee on Genetics, Health, and Society; the Secretary's Advisory Committee on Heritable Disorders in Newborns and Children; and representatives of newborn

  4. Significance of family and peer support for metabolic control of type 1 diabetes in adolescents

    Directory of Open Access Journals (Sweden)

    Đurović Dušanka

    2009-01-01

    Full Text Available The aim of the paper was to explore the significance of family and peer support for metabolic control of Type 1 diabetes in adolescents. Metabolic control refers to maintenance of acceptable blood glucose level thus diminishing risk for chronic complications. It involves regular insulin shots, measuring blood glucose and keeping diary, as the daily based self-control. Regular visits to endocrinologist and screening for chronic complications are compulsory. The sample comprised 79 adolescents age 10-17 years with diagnose of Type 1 diabetes and properly treated at the institute. The sample was divided in two groups - with good (N=40 and poor (N=39 metabolic control. A criterium for good metabolic control was glycosilated hemoglobin less than 7,6%. Social support was measured by Social Support Scale consisting of two parts - the first for estimation of registered family support (based upon modified Perceived Social Support Family Scale and the second for estimation of registered friends' support (modified Perceived Social Support Friend Scale. Adolescents with good metabolic control referred statistically more significant social support in the family, unlike the group with poor metabolic control. Considering peer social support, there was no statistically significant difference. Positive family history for diabetes also appeared to be directly linked to good metabolic control.

  5. [Pharmaceutical product quality control and good manufacturing practices].

    Science.gov (United States)

    Hiyama, Yukio

    2010-01-01

    This report describes the roles of Good Manufacturing Practices (GMP) in pharmaceutical product quality control. There are three keys to pharmaceutical product quality control. They are specifications, thorough product characterization during development, and adherence to GMP as the ICH Q6A guideline on specifications provides the most important principles in its background section. Impacts of the revised Pharmaceutical Affairs Law (rPAL) which became effective in 2005 on product quality control are discussed. Progress of ICH discussion for Pharmaceutical Development (Q8), Quality Risk Management (Q9) and Pharmaceutical Quality System (Q10) are reviewed. In order to reconstruct GMP guidelines and GMP inspection system in the regulatory agencies under the new paradigm by rPAL and the ICH, a series of Health Science studies were conducted. For GMP guidelines, product GMP guideline, technology transfer guideline, laboratory control guideline and change control system guideline were written. For the GMP inspection system, inspection check list, inspection memo and inspection scenario were proposed also by the Health Science study groups. Because pharmaceutical products and their raw materials are manufactured and distributed internationally, collaborations with other national authorities are highly desired. In order to enhance the international collaborations, consistent establishment of GMP inspection quality system throughout Japan will be essential.

  6. Metabolic Control of Redox and Redox Control of Metabolism in Plants

    Science.gov (United States)

    Fernie, Alisdair R.

    2014-01-01

    Abstract Significance: Reduction-oxidation (Redox) status operates as a major integrator of subcellular and extracellular metabolism and is simultaneously itself regulated by metabolic processes. Redox status not only dominates cellular metabolism due to the prominence of NAD(H) and NADP(H) couples in myriad metabolic reactions but also acts as an effective signal that informs the cell of the prevailing environmental conditions. After relay of this information, the cell is able to appropriately respond via a range of mechanisms, including directly affecting cellular functioning and reprogramming nuclear gene expression. Recent Advances: The facile accession of Arabidopsis knockout mutants alongside the adoption of broad-scale post-genomic approaches, which are able to provide transcriptomic-, proteomic-, and metabolomic-level information alongside traditional biochemical and emerging cell biological techniques, has dramatically advanced our understanding of redox status control. This review summarizes redox status control of metabolism and the metabolic control of redox status at both cellular and subcellular levels. Critical Issues: It is becoming apparent that plastid, mitochondria, and peroxisome functions influence a wide range of processes outside of the organelles themselves. While knowledge of the network of metabolic pathways and their intraorganellar redox status regulation has increased in the last years, little is known about the interorganellar redox signals coordinating these networks. A current challenge is, therefore, synthesizing our knowledge and planning experiments that tackle redox status regulation at both inter- and intracellular levels. Future Directions: Emerging tools are enabling ever-increasing spatiotemporal resolution of metabolism and imaging of redox status components. Broader application of these tools will likely greatly enhance our understanding of the interplay of redox status and metabolism as well as elucidating and

  7. Role of metabolic control on diabetic nephropathy

    Directory of Open Access Journals (Sweden)

    Macedo Célia Sperandéo

    2002-01-01

    Full Text Available OBJECTIVE: The aim of this investigation was studying the influence of glucose metabolic control on diabetic nephropathy. The authors observed the effect of acarbose, insulin, and both drugs on the metabolic control and development of mesangial enlargement of kidney glomeruli in alloxan-diabetic rats. METHODS: Five groups of Wistar rats were used: normal rats (N, non-treated alloxan-diabetic rats (D, alloxan-diabetic rats treated with acarbose (AD, alloxan-diabetic rats treated with insulin (ID, and alloxan-diabetic rats treated with insulin plus acarbose (IAD. The following parameters were evaluated: body weight; water and food intake; diuresis; blood and urine glucose levels; and the kidney lesions: mesangial enlargement and tubule cell vacuolization. Renal lesions were analysed using a semi-quantitative score 1, 3, 6, 9, and 12 months after diabetes induction. RESULTS: Diabetic rats showed a marked increase of glycemia, urinary glucose levels, diuresis, water and food intake, and weight loss, while the treated diabetic rats showed significant decreased levels of these parameters. The most satisfactory metabolic control was that of diabetic rats treated with acarbose + insulin. There was a significant mesangial enlargement in diabetic rats compared to normal rats from the third up to the 12th month after diabetes induction, with a significant difference between the animals treated with acarbose + insulin and non-treated diabetic rats. A difference between the animals treated with acarbose or insulin alone and non-treated diabetics rats was not seen. CONCLUSIONS: The authors discuss the results stressing the role of diabetic metabolic control in the prevention of diabetic nephropathy.

  8. Sleep-Wake Differences in Relative Regional Cerebral Metabolic Rate for Glucose among Patients with Insomnia Compared with Good Sleepers

    Science.gov (United States)

    Kay, Daniel B.; Karim, Helmet T.; Soehner, Adriane M.; Hasler, Brant P.; Wilckens, Kristine A.; James, Jeffrey A.; Aizenstein, Howard J.; Price, Julie C.; Rosario, Bedda L.; Kupfer, David J.; Germain, Anne; Hall, Martica H.; Franzen, Peter L.; Nofzinger, Eric A.; Buysse, Daniel J.

    2016-01-01

    Study Objectives: The neurobiological mechanisms of insomnia may involve altered patterns of activation across sleep-wake states in brain regions associated with cognition, self-referential processes, affect, and sleep-wake promotion. The objective of this study was to compare relative regional cerebral metabolic rate for glucose (rCMRglc) in these brain regions across wake and nonrapid eye movement (NREM) sleep states in patients with primary insomnia (PI) and good sleeper controls (GS). Methods: Participants included 44 PI and 40 GS matched for age (mean = 37 y old, range 21–60), sex, and race. We conducted [18F]fluoro-2-deoxy-d-glucose positron emission tomography scans in PI and GS during both morning wakefulness and NREM sleep at night. Repeated measures analysis of variance was used to test for group (PI vs. GS) by state (wake vs. NREM sleep) interactions in relative rCMRglc. Results: Significant group-by-state interactions in relative rCMRglc were found in the precuneus/posterior cingulate cortex, left middle frontal gyrus, left inferior/superior parietal lobules, left lingual/fusiform/occipital gyri, and right lingual gyrus. All clusters were significant at Pcorrected sleep and wakefulness. Significant group-by-state interactions in relative rCMRglc suggest that insomnia is associated with impaired disengagement of brain regions involved in cognition (left frontoparietal), self-referential processes (precuneus/posterior cingulate), and affect (left middle frontal, fusiform/lingual gyri) during NREM sleep, or alternatively, to impaired engagement of these regions during wakefulness. Citation: Kay DB, Karim HT, Soehner AM, Hasler BP, Wilckens KA, James JA, Aizenstein HJ, Price JC, Rosario BL, Kupfer DJ, Germain A, Hall MH, Franzen PL, Nofzinger EA, Buysse DJ. Sleep-wake differences in relative regional cerebral metabolic rate for glucose among patients with insomnia compared with good sleepers. SLEEP 2016;39(10):1779–1794. PMID:27568812

  9. Metabolic control of feed intake: implications for metabolic disease of fresh cows.

    Science.gov (United States)

    Allen, Michael S; Piantoni, Paola

    2013-07-01

    The objective of this article is to discuss metabolic control of feed intake in the peripartum period and its implications for metabolic disease of fresh cows. Understanding how feed intake is controlled during the transition from gestation to lactation is critical to both reduce risk and successfully treat many metabolic diseases. Copyright © 2013. Published by Elsevier Inc.

  10. Coffee consumption, metabolic syndrome and clinical severity of psoriasis: good or bad stuff?

    Science.gov (United States)

    Barrea, Luigi; Muscogiuri, Giovanna; Di Somma, Carolina; Annunziata, Giuseppe; Megna, Matteo; Falco, Andrea; Balato, Anna; Colao, Annamaria; Savastano, Silvia

    2018-05-01

    Despite the wide consumption of coffee, its anti-inflammatory effect on clinical severity of psoriasis is still debatable. The aim of this study was to evaluate the association between the coffee consumption and clinical severity of psoriasis in a sample of patients stratified according to the presence of the metabolic syndrome (MetS) and smoking. This cross-sectional case-control observational study was conducted on 221 treatment-naïve psoriatic patients. Lifestyle habits, anthropometric measures, clinical and biochemical evaluations were obtained. Clinical severity of psoriasis was assessed by Psoriasis Area and Severity Index (PASI) score. Data on energy caloric intake and coffee consumption were collected using a 7-day food diary record. The coffee consumption was analyzed as coffee intake (consumers and non-consumers) and daily servings (range 0-4 servings/day). Coffee consumers have a lower PASI score vs non-consumers (p < 0.001). The lowest PASI score and MetS prevalence were found in patients consuming 3 cups of coffee/day (p < 0.001), which was also the most common daily serving (34.8%), whereas the highest PASI score was found among those drinking ≥ 4 cups/day. Grouping the case patients according to smoking and MetS, the best odds of PASI score was observed in those drinking 3 cups of coffee per day and no smokers, after adjusting for total energy intake (OR 74.8; p < 0.001). As a novel finding, we reported a negative association between coffee intake, MetS prevalence and clinical severity of psoriasis. The evaluation of the anti-inflammatory effect of coffee on clinical severity of psoriasis, whose metabolic risk increases along with its clinical severity, could be of great importance from a public health perspective.

  11. Molecular, metabolic, and genetic control: An introduction

    Science.gov (United States)

    Tyson, John J.; Mackey, Michael C.

    2001-03-01

    The living cell is a miniature, self-reproducing, biochemical machine. Like all machines, it has a power supply, a set of working components that carry out its necessary tasks, and control systems that ensure the proper coordination of these tasks. In this Special Issue, we focus on the molecular regulatory systems that control cell metabolism, gene expression, environmental responses, development, and reproduction. As for the control systems in human-engineered machines, these regulatory networks can be described by nonlinear dynamical equations, for example, ordinary differential equations, reaction-diffusion equations, stochastic differential equations, or cellular automata. The articles collected here illustrate (i) a range of theoretical problems presented by modern concepts of cellular regulation, (ii) some strategies for converting molecular mechanisms into dynamical systems, (iii) some useful mathematical tools for analyzing and simulating these systems, and (iv) the sort of results that derive from serious interplay between theory and experiment.

  12. Good control practices underlined by an on-line fuzzy control database

    Directory of Open Access Journals (Sweden)

    Alonso, M. V.

    1994-04-01

    Full Text Available In the olive oil trade, control systems that automate extraction processes, cutting production costs and increasing processing capacity without losing quality, are always desirable. The database structure of an on-line fuzzy control of centrifugation systems and the algorithms used to attain the best control conditions are analysed. Good control practices are suggested to obtain virgin olive oil of prime quality.

    In the olive oil trade, control systems that automate extraction processes, cutting production costs and increasing processing capacity without losing quality, are always desirable. The database structure of an on-line fuzzy control of centrifugation systems and the algorithms used to attain the best control conditions are analysed. Good control practices are suggested to obtain virgin olive oil of prime quality.

  13. Hematopoietic stem cell fate through metabolic control.

    Science.gov (United States)

    Ito, Kyoko; Ito, Keisuke

    2018-05-25

    Hematopoietic stem cells (HSCs) maintain a quiescent state in the bone marrow to preserve their self-renewal capacity, but also undergo cell divisions as required. Organelles such as the mitochondria sustain cumulative damage during these cell divisions, and this damage may eventually compromise the cells' self-renewal capacity. HSC divisions result in either self-renewal or differentiation, with the balance between the two directly impacting hematopoietic homeostasis; but the heterogeneity of available HSC-enriched fractions, together with the technical challenges of observing HSC behavior, has long hindered the analysis of individual HSCs, and prevented the elucidation of this process. However, recent advances in genetic models, metabolomics analyses and single-cell approaches have revealed the contributions made to HSC self-renewal by metabolic cues, mitochondrial biogenesis, and autophagy/mitophagy, which have highlighted mitochondrial quality as a key control factor in the equilibrium of HSCs. A deeper understanding of precisely how specific modes of metabolism control HSC fate at the single cell level is therefore not only of great biological interest, but will have clear clinical implications for the development of therapies for hematological disease. Copyright © 2018. Published by Elsevier Inc.

  14. Bilateral Diabetic Papillopathy and Metabolic Control

    DEFF Research Database (Denmark)

    Ostri, Christoffer; Lund-Andersen, Henrik; Sander, Birgit

    2010-01-01

    OBJECTIVE: The pathogenesis of diabetic papillopathy largely is unknown, but case reports suggest that it may follow rapidly improved metabolic control. The present study was designed to investigate this hypothesis. DESIGN: Retrospective case-control study. PARTICIPANTS: Two thousand sixty......-six patients with type 1 diabetes. METHODS: Review of clinical, photographic, and clinical chemistry records from a large diabetology and ophthalmology unit between 2001 and 2008. MAIN OUTCOME MEASURES: Simultaneous, bilateral diabetic papillopathy. RESULTS: The mean follow-up was 4.9 years. During 10 020...... patient-years of observation, bilateral diabetic papillopathy developed in 5 patients. During the year preceding this incident, all 5 patients had experienced a decrease in glycosylated hemoglobin A(1c) (HbA(1C)) at a maximum rate of -2.5 (mean) percentage points per quarter year, which was significantly...

  15. It must be my metabolism: Metabolic control of mind

    Directory of Open Access Journals (Sweden)

    Dana M Small

    2014-07-01

    relationship between the reinforcing potency of sugared solutions and the metabolic effects that follow their consumption (16, also see the abstract of I. de Araujo. We therefore hypothesized that metabolic response provides the critical signal necessary to condition preference. To test this prediction in humans we designed a flavor nutrient conditioning study in which participants first rated their liking for novel flavored beverages and then, over a three week-long conditioning protocol, alternately ingested one of the flavored beverages with 112.5 kcal from maltodextrin, a tasteless and odorless polysaccharide that breaks down into glucose, and another flavored beverage with no calories added. Plasma glucose was measured before and after each of the drinks’ consumption as a proxy measure of metabolic response, assuming that glucose oxidation depends upon the level of circulating glucose. For each participant flavor-calorie pairings were held constant but the identity of the conditioned flavors were counterbalanced across participants. Following the exposure phase, participants’ liking of, and brain responses to, non-caloric versions of the flavors were assessed. We predicted that change in plasma glucose produced by beverage consumption during the exposure sessions would be associated with neural responses in dopamine source and target regions to the calorie predictive flavor. As predicted, response in the ventral striatum and hypothalamus to the calorie-predictive flavor (CS+ vs. non the noncaloric-predictive flavor (CS- was strongly associated with the changes in plasma glucose levels produced by ingestion of these same beverages when consumed previously either with (CS+ or without (CS- calories (17. Specifically, the greater the increase in circulating glucose occurring post ingestion of the beverage containing 112.5 kcal from maltodextrin versus the noncaloric drink, the stronger was the brain response to the CS+ compared to the CS- flavor. Importantly, because each

  16. Precision metabolic engineering: The design of responsive, selective, and controllable metabolic systems.

    Science.gov (United States)

    McNerney, Monica P; Watstein, Daniel M; Styczynski, Mark P

    2015-09-01

    Metabolic engineering is generally focused on static optimization of cells to maximize production of a desired product, though recently dynamic metabolic engineering has explored how metabolic programs can be varied over time to improve titer. However, these are not the only types of applications where metabolic engineering could make a significant impact. Here, we discuss a new conceptual framework, termed "precision metabolic engineering," involving the design and engineering of systems that make different products in response to different signals. Rather than focusing on maximizing titer, these types of applications typically have three hallmarks: sensing signals that determine the desired metabolic target, completely directing metabolic flux in response to those signals, and producing sharp responses at specific signal thresholds. In this review, we will first discuss and provide examples of precision metabolic engineering. We will then discuss each of these hallmarks and identify which existing metabolic engineering methods can be applied to accomplish those tasks, as well as some of their shortcomings. Ultimately, precise control of metabolic systems has the potential to enable a host of new metabolic engineering and synthetic biology applications for any problem where flexibility of response to an external signal could be useful. Copyright © 2015 International Metabolic Engineering Society. Published by Elsevier Inc. All rights reserved.

  17. Central nervous system control of triglyceride metabolism

    NARCIS (Netherlands)

    Geerling, Johanna Janetta (Janine)

    2013-01-01

    This thesis describes the role of the brain in the regulation of peripheral triglyceride metabolism, in the context of the metabolic syndrome. Based on various pharmacological studies we described the role of two hormones, insulin and glucagon-like peptide-1, in the production and clearance of

  18. Adherence to two methods of education and metabolic control in ...

    African Journals Online (AJOL)

    BACKGROUND: Education in diabetes optimizes metabolic control, prevents acute and chronic complications, and improves quality of life. Our main objective was to evaluate if a better metabolic control is achieved in diabetic patients undergoing a program of intensive interactive care than in those with traditional care and ...

  19. The effect of metabolic control on hemodynamics in short-term insulin-dependent diabetic patients

    DEFF Research Database (Denmark)

    Mathiesen, E R; Hilsted, J; Feldt-Rasmussen, B

    1985-01-01

    Hemodynamics variables (heart rate, arterial blood pressure, cardiac output, hepato-splanchnic blood flow, forearm blood flow, and plasma catecholamines) were measured during good (median blood glucose 4.7 mmol/L) and poor (median blood glucose 16.3 mmol/L) metabolic control in eight young, short...

  20. Sleep Control, GPCRs, and Glucose Metabolism.

    Science.gov (United States)

    Tsuneki, Hiroshi; Sasaoka, Toshiyasu; Sakurai, Takeshi

    2016-09-01

    Modern lifestyles prolong daily activities into the nighttime, disrupting circadian rhythms, which may cause sleep disturbances. Sleep disturbances have been implicated in the dysregulation of blood glucose levels and reported to increase the risk of type 2 diabetes (T2D) and diabetic complications. Sleep disorders are treated using anti-insomnia drugs that target ionotropic and G protein-coupled receptors (GPCRs), including γ-aminobutyric acid (GABA) agonists, melatonin agonists, and orexin receptor antagonists. A deeper understanding of the effects of these medications on glucose metabolism and their underlying mechanisms of action is crucial for the treatment of diabetic patients with sleep disorders. In this review we focus on the beneficial impact of sleep on glucose metabolism and suggest a possible strategy for therapeutic intervention against sleep-related metabolic disorders. Copyright © 2016. Published by Elsevier Ltd.

  1. Hypothalamic control of energy and glucose metabolism.

    Science.gov (United States)

    Sisley, Stephanie; Sandoval, Darleen

    2011-09-01

    The central nervous system (CNS), generally accepted to regulate energy homeostasis, has been implicated in the metabolic perturbations that either cause or are associated with obesity. Normally, the CNS receives hormonal, metabolic, and neuronal input to assure adequate energy levels and maintain stable energy homeostasis. Recent evidence also supports that the CNS uses these same inputs to regulate glucose homeostasis and this aspect of CNS regulation also becomes impaired in the face of dietary-induced obesity. This review focuses on the literature surrounding hypothalamic regulation of energy and glucose homeostasis and discusses how dysregulation of this system may contribute to obesity and T2DM.

  2. Good intentions and received wisdom are not good enough: the need for controlled trials in public health.

    Science.gov (United States)

    Macintyre, Sally

    2011-07-01

    In the 1970s Archie Cochrane noted that many healthcare procedures and forms of organisation lacked evidence of effectiveness and efficiency, and argued for improved methods of evaluation, moving from clinical opinion and observation to randomised controlled trials (RCTs). His arguments gradually became accepted in medicine, but there has been considerable resistance among policymakers and researchers to their application to social and public health interventions. This essay argues that opposition to RCTs in public health is often based on a false distinction between healthcare and community settings, and sometimes on a misunderstanding of the principles of RCTs in health care. It suggests that just as in medicine, good intentions and received wisdom are not a sufficient basis for making public policy and allocating public funds for social or health improvement.

  3. Mitochondrial quality control pathways as determinants of metabolic health

    NARCIS (Netherlands)

    Held, Ntsiki M.; Houtkooper, Riekelt H.

    2015-01-01

    Mitochondrial function is key for maintaining cellular health, while mitochondrial failure is associated with various pathologies, including inherited metabolic disorders and age-related diseases. In order to maintain mitochondrial quality, several pathways of mitochondrial quality control have

  4. Comprehensive assessment of variables affecting metabolic control in patients with type 2 diabetes mellitus in Jordan.

    Science.gov (United States)

    Qteishat, Rola Reyad; Ghananim, Abdel Rahman Al

    2016-01-01

    The aim of the study was to identify variables affecting metabolic control among diabetic patients treated at diabetes and endocrine clinic in Jordan. A total of 200 patients were studied by using a cross sectional study design. Data were collected from patients' medical records, glycemic control tests and prestructured questionnaires about variables that were potentially important based on previous researches and clinical judgment: Adherence evaluation, Patients' knowledge about drug therapy and non-pharmacological therapy, Anxiety and depression, Beliefs about diabetes treatment (benefits and barriers of treatment), Knowledge about treatment goals, Knowledge about diabetes, Self efficacy, and Social support. The mean (±SD) age was 53.5 (±10.38) years and mean HbA1c was 8.4 (±1.95). In the multivariate analysis, education level, and self efficacy found to have significantly independent association with metabolic control (Pknowledge and high self efficacy was significant in patients with good metabolic control. Emphasizing the importance of continuous educational programs and improving the self efficacy as well, could warrant achieving good metabolic control. Copyright © 2015 Diabetes India. Published by Elsevier Ltd. All rights reserved.

  5. Metabolic control of the insecticides safety use

    Directory of Open Access Journals (Sweden)

    L.I. Solomenko

    2016-06-01

    Full Text Available The results of the conducted research affirm that the phosphororganic insecticides utilization can lead to the break in the nitrogen metabolism, breaking the protein formation, reducing the protein molecules renewal, causing the amino acid and amides accumulation in the active state. It has been revealed that the translocation and transformation of the insecticides under consideration are more closely connected with the changes of insoluble protein fraction. The stagnation point of the Phosphamide and Kaunter impact on the plant has been determined. And only the use of the preparation in optimal norms can influence stimulatingly the course of the process under consideration.

  6. Metabolic control by S6 kinases depends on dietary lipids.

    Directory of Open Access Journals (Sweden)

    Tamara R Castañeda

    Full Text Available Targeted deletion of S6 kinase (S6K 1 in mice leads to higher energy expenditure and improved glucose metabolism. However, the molecular mechanisms controlling these effects remain to be fully elucidated. Here, we analyze the potential role of dietary lipids in regulating the mTORC1/S6K system. Analysis of S6K phosphorylation in vivo and in vitro showed that dietary lipids activate S6K, and this effect is not dependent upon amino acids. Comparison of male mice lacking S6K1 and 2 (S6K-dko with wt controls showed that S6K-dko mice are protected against obesity and glucose intolerance induced by a high-fat diet. S6K-dko mice fed a high-fat diet had increased energy expenditure, improved glucose tolerance, lower fat mass gain, and changes in markers of lipid metabolism. Importantly, however, these metabolic phenotypes were dependent upon dietary lipids, with no such effects observed in S6K-dko mice fed a fat-free diet. These changes appear to be mediated via modulation of cellular metabolism in skeletal muscle, as shown by the expression of genes involved in energy metabolism. Taken together, our results suggest that the metabolic functions of S6K in vivo play a key role as a molecular interface connecting dietary lipids to the endogenous control of energy metabolism.

  7. Effect of dietary regime on metabolic control in phenylketonuria: Is exact calculation of phenylalanine intake really necessary?

    Directory of Open Access Journals (Sweden)

    Carmen Rohde

    2015-12-01

    Conclusion: Exact calculation of Phe content of all food is not necessary to achieve good metabolic control in children and adolescents with PKU. Excluding special low protein food, as well as fruit and vegetables from calculation of Phe-intake has no impact on metabolic control. However including protein rich food into the diet and simply estimating all Phe-intake appears insufficient. The simplification of dietary regime may be helpful in enhancing acceptability and feasibility.

  8. Slave nodes and the controllability of metabolic networks

    International Nuclear Information System (INIS)

    Kim, Dong-Hee; Motter, Adilson E

    2009-01-01

    Recent work on synthetic rescues has shown that the targeted deletion of specific metabolic genes can often be used to rescue otherwise non-viable mutants. This raises a fundamental biophysical question: to what extent can the whole-cell behavior of a large metabolic network be controlled by constraining the flux of one or more reactions in the network? This touches upon the issue of the number of degrees of freedom contained by one such network. Using the metabolic network of Escherichia coli as a model system, here we address this question theoretically by exploring not only reaction deletions, but also a continuum of all possible reaction expression levels. We show that the behavior of the metabolic network can be largely manipulated by the pinned expression of a single reaction. In particular, a relevant fraction of the metabolic reactions exhibits canalizing interactions, in that the specification of one reaction flux determines cellular growth as well as the fluxes of most other reactions in optimal steady states. The activity of individual reactions can thus be used as surrogates to monitor and possibly control cellular growth and other whole-cell behaviors. In addition to its implications for the study of control processes, our methodology provides a new approach to study how the integrated dynamics of the entire metabolic network emerges from the coordinated behavior of its component parts.

  9. Hypothalamic control of energy metabolism via the autonomic nervous system

    NARCIS (Netherlands)

    Kalsbeek, A.; Bruinstroop, E.; Yi, C. X.; Klieverik, L. P.; La Fleur, S. E.; Fliers, E.

    2010-01-01

    The hypothalamic control of hepatic glucose production is an evident aspect of energy homeostasis. In addition to the control of glucose metabolism by the circadian timing system, the hypothalamus also serves as a key relay center for (humoral) feedback information from the periphery, with the

  10. Metabolic control of female puberty: potential therapeutic targets.

    Science.gov (United States)

    Castellano, Juan M; Tena-Sempere, Manuel

    2016-10-01

    The onset of puberty in females is highly sensitive to the nutritional status and the amount of energy reserves of the organism. This metabolic information is sensed and transmitted to hypothalamic GnRH neurons, considered to be ultimately responsible for triggering puberty through the coordinated action of different peripheral hormones, central neurotransmitters, and molecular mediators. This article will review and discuss (i) the relevant actions of the adipose hormone leptin, as a stimulatory/permissive signal, and the gut hormone ghrelin, as an inhibitory factor, in the metabolic control of female puberty; (ii) the crucial role of the hypothalamic kisspeptin neurons, recently emerged as essential gatekeepers of puberty, in transmitting this metabolic information to GnRH neurons; and (iii) the potential involvement of key cellular energy sensors, such as mTOR, as molecular mediators in this setting. The thorough characterization of the physiological roles of the above elements in the metabolic control of female puberty, along with the discovery of novel factors, pathways, and mechanisms involved, will promote our understanding of the complex networks connecting metabolism and puberty and, ultimately, will aid in the design of target-specific treatments for female pubertal disorders linked to conditions of metabolic stress.

  11. Metabolic sensing neurons and the control of energy homeostasis.

    Science.gov (United States)

    Levin, Barry E

    2006-11-30

    The brain and periphery carry on a constant conversation; the periphery informs the brain about its metabolic needs and the brain provides for these needs through its control of somatomotor, autonomic and neurohumoral pathways involved in energy intake, expenditure and storage. Metabolic sensing neurons are the integrators of a variety of metabolic, humoral and neural inputs from the periphery. Such neurons, originally called "glucosensing", also respond to fatty acids, hormones and metabolites from the periphery. They are integrated within neural pathways involved in the regulation of energy homeostasis. Unlike most neurons, they utilize glucose and other metabolites as signaling molecules to regulate their membrane potential and firing rate. For glucosensing neurons, glucokinase acts as the rate-limiting step in glucosensing while the pathways that mediate responses to metabolites like lactate, ketone bodies and fatty acids are less well characterized. Many metabolic sensing neurons also respond to insulin and leptin and other peripheral hormones and receive neural inputs from peripheral organs. Each set of afferent signals arrives with different temporal profiles and by different routes and these inputs are summated at the level of the membrane potential to produce a given neural firing pattern. In some obese individuals, the relative sensitivity of metabolic sensing neurons to various peripheral inputs is genetically reduced. This may provide one mechanism underlying their propensity to become obese when exposed to diets high in fat and caloric density. Thus, metabolic sensing neurons may provide a potential therapeutic target for the treatment of obesity.

  12. Free-range pork: Innovation and control of a new credence good

    DEFF Research Database (Denmark)

    Philipsen, Kristian; Andersen, Esben Sloth

    -range pork should be analysed as a "credence good". In this way a whole set of problems related to production and sale of this kind of pork becomes clear. 2. The problem of evaluating a credence good is intensified in the case of free-range pork, because the responsibility for the credence quality is divided...... among a large number of parties, and the fact that there is no common "standard" or "definition" of what is meant by free-range pork. Thi aggravates the control aspect of free-range pork. This report focuses on this point. 3. The study's empirical basis is three cases, one Dutch and two Danish, about...... withdrawn from the Danish free-range pork market. 8. The Dutch system with an independent control organisation may be a paradigm or a standard for establishing an inspection system for credence goods. The Dutch system, therefore, seems to be more advanced than the other control systems with regard...

  13. Metabolic control analysis of xylose catabolism in Aspergillus

    NARCIS (Netherlands)

    Prathumpai, W.; Gabelgaard, J.B.; Wanchanthuek, P.; Vondervoort, van de P.J.I.; Groot, de M.J.L.; McIntyre, M.; Nielsen, J.

    2003-01-01

    A kinetic model for xylose catabolism in Aspergillus is proposed. From a thermodynamic analysis it was found that the intermediate xylitol will accumulate during xylose catabolism. Use of the kinetic model allowed metabolic control analysis (MCA) of the xylose catabolic pathway to be carried out,

  14. Dynamic optimal metabolic control theory: a cybernetic approach for modelling of the central nitrogen metabolism of S. cerevisiae

    NARCIS (Netherlands)

    Riel, van N.A.W.; Giuseppin, M.L.F.; Verrips, C.T.

    2000-01-01

    The theory of dynamic optimal metabolic control (DOMC), as developed by Giuseppin and Van Riel (Metab. Eng., 2000), is applied to model the central nitrogen metabolism (CNM) in Saccharomyces cerevisiae. The CNM represents a typical system encountered in advanced metabolic engineering. The CNM is the

  15. Transcriptional switches in the control of macronutrient metabolism.

    Science.gov (United States)

    Wise, Alan

    2008-06-01

    This review shows how some transcription factors respond to alterations in macronutrients. Carbohydrates induce enzymes for their metabolism and fatty acid synthesis. Fatty acids reduce carbohydrate processing, induce enzymes for their metabolism, and increase both gluconeogenesis and storage of fat. Fat stores help control carbohydrate uptake by other cells. The following main transcription factors are discussed: carbohydrate response element-binding protein; sterol regulatory element-binding protein-1c, cyclic AMP response element-binding protein, peroxisome proliferator-activated receptor-alpha, and peroxisome proliferator-activated receptor-gamma.

  16. Sleep and metabolic control: waking to a problem?

    Science.gov (United States)

    Trenell, Michael I; Marshall, Nathaniel S; Rogers, Naomi L

    2007-01-01

    1. The aim of the present review is to outline: (i) the association between sleep and metabolism; (ii) how sleep duration influences the development of disease; and (iii) how sex differences, ageing and obesity may potentially influence the relationship between sleep, metabolic control and subsequent disease. 2. Sleep is associated with a number of endocrine changes, including a change in insulin action in healthy young individuals. Sleep duration shows a prospective U-shaped relationship with all-cause mortality, cardiovascular disease and Type 2 diabetes. 3. Chronic sleep restriction is becoming more common. Experimental sleep restriction impedes daytime glucose control and increases appetite. 4. The sex hormones oestrogen and testosterone influence sleep duration and quality and may account for sex differences in the prevalence of sleep-related disorders. 5. Ageing is associated with a decreased sleep duration, decreased muscle mass and impaired insulin action. 6. Obesity impairs insulin action and is associated with the incidence and severity of obstructive sleep apnoea. 7. Sleep plays an integral role in metabolic control. Consequently, insufficient sleep may represent a modifiable risk factor for the development of Type 2 diabetes. The challenge ahead is to identify how sex differences, ageing and obesity could potentially influence the relationship between sleep and metabolism.

  17. Controlling cell-free metabolism through physiochemical perturbations.

    Science.gov (United States)

    Karim, Ashty S; Heggestad, Jacob T; Crowe, Samantha A; Jewett, Michael C

    2018-01-01

    Building biosynthetic pathways and engineering metabolic reactions in cells can be time-consuming due to complexities in cellular metabolism. These complexities often convolute the combinatorial testing of biosynthetic pathway designs needed to define an optimal biosynthetic system. To simplify the optimization of biosynthetic systems, we recently reported a new cell-free framework for pathway construction and testing. In this framework, multiple crude-cell extracts are selectively enriched with individual pathway enzymes, which are then mixed to construct full biosynthetic pathways on the time scale of a day. This rapid approach to building pathways aids in the study of metabolic pathway performance by providing a unique freedom of design to modify and control biological systems for both fundamental and applied biotechnology. The goal of this work was to demonstrate the ability to probe biosynthetic pathway performance in our cell-free framework by perturbing physiochemical conditions, using n-butanol synthesis as a model. We carried out three unique case studies. First, we demonstrated the power of our cell-free approach to maximize biosynthesis yields by mapping physiochemical landscapes using a robotic liquid-handler. This allowed us to determine that NAD and CoA are the most important factors that govern cell-free n-butanol metabolism. Second, we compared metabolic profile differences between two different approaches for building pathways from enriched lysates, heterologous expression and cell-free protein synthesis. We discover that phosphate from PEP utilization, along with other physiochemical reagents, during cell-free protein synthesis-coupled, crude-lysate metabolic system operation inhibits optimal cell-free n-butanol metabolism. Third, we show that non-phosphorylated secondary energy substrates can be used to fuel cell-free protein synthesis and n-butanol biosynthesis. Taken together, our work highlights the ease of using cell-free systems to explore

  18. [Metabolic control in children and adolescents with type 1 diabetes].

    Science.gov (United States)

    Díaz-Cárdenas, Claudia; Wong, Carolina; Vargas Catalán, Nelson A

    2016-01-01

    Type 1 diabetes mellitus (T1D) is an important disease in children and adolescent being a major risk factor for early morbidity and mortality. To know the degree of metabolic control and prevalence of cardiovascular risk factors in T1D patients. Retrospective study including patients under 19 years of age with T1D controlled at a Chilean hospital in 2011. 94 patients were evaluated (average age at diagnosis: 7.3 years; current age: 11,9 years; evolution time: 4.5 years). Seventy-nine percent (79.8%) of patients presented glycated hemoglobin (HbA1c) over the recommended level with an average of 8.9%. The group between 13 and 19 years of age exhibited the worst metabolic control (86% with HbA1c abnormal levels). Overweight or obesity occurred in 26.6% of patients, 20.3% had LDL >100mg/dl and 4.2% had hypertension. Only about twenty percent of patients had adequate metabolic control as measured by HbA1c, although cardiovascular risk profile was acceptable. Therapeutic and educational efforts must be reinforced mainly in adolescents, emphasizing the importance of adequate nutritional management as a primary method to treat this entity. Copyright © 2015 Sociedad Chilena de Pediatría. Publicado por Elsevier España, S.L.U. All rights reserved.

  19. Neuroendocrine control by kisspeptins: role in metabolic regulation of fertility.

    Science.gov (United States)

    Navarro, Victor M; Tena-Sempere, Manuel

    2011-09-13

    The neurohormonal control of reproduction involves a hierarchical network of central and peripheral signals in the hypothalamic-pituitary-gonadal (HPG) axis. Development and function of this neuroendocrine system is the result of a lifelong delicate balance between endogenous regulators and environmental cues, including nutritional and metabolic factors. Kisspeptins are the peptide products of KISS1, which operate via the G-protein-coupled receptor GPR54 (also known as Kiss1R). These peptides have emerged as essential upstream regulators of neurons secreting gonadotropin-releasing hormone (GnRH), the major hypothalamic node for the stimulatory control of the HPG axis. They are potent elicitors of gonadotropin secretion in various species and physiological settings. Moreover, Kiss1 neurons in the hypothalamus participate in crucial features of reproductive maturation and function, such as brain-level sex differentiation, puberty onset and the neuroendocrine regulation of gonadotropin secretion and ovulation. Cotransmitters of Kiss1 neurons, such as neurokinin B, with roles in controlling the HPG axis have been identified by genetic, neuroanatomical and physiological studies. In addition, a putative role has been proposed for Kiss1 neurons in transmitting metabolic information to GnRH neurons, although the precise mechanisms are as yet unclear. In this Review, we present the major reproductive features of kisspeptins, especially their interplay with neurokinin B and potential roles in the metabolic control of puberty and fertility, and suggest new avenues for research.

  20. Metabolic syndrome and atypical antipsychotics: Possibility of prediction and control.

    Science.gov (United States)

    Franch Pato, Clara M; Molina Rodríguez, Vicente; Franch Valverde, Juan I

    Schizophrenia and other psychotic disorders are associated with high morbidity and mortality, due to inherent health factors, genetic factors, and factors related to psychopharmacological treatment. Antipsychotics, like other drugs, have side-effects that can substantially affect the physical health of patients, with substantive differences in the side-effect profile and in the patients in which these side-effects occur. To understand and identify these risk groups could help to prevent the occurrence of the undesired effects. A prospective study, with 24 months follow-up, was conducted in order to analyse the physical health of severe mental patients under maintenance treatment with atypical antipsychotics, as well as to determine any predictive parameters at anthropometric and/or analytical level for good/bad outcome of metabolic syndrome in these patients. There were no significant changes in the physical and biochemical parameters individually analysed throughout the different visits. The baseline abdominal circumference (lambda Wilks P=.013) and baseline HDL-cholesterol levels (lambda Wilks P=.000) were the parameters that seem to be more relevant above the rest of the metabolic syndrome constituents diagnosis criteria as predictors in the long-term. In the search for predictive factors of metabolic syndrome, HDL-cholesterol and abdominal circumference at the time of inclusion were selected, as such that the worst the baseline results were, the higher probability of long-term improvement. Copyright © 2016 SEP y SEPB. Publicado por Elsevier España, S.L.U. All rights reserved.

  1. Leptin and the central nervous system control of glucose metabolism.

    Science.gov (United States)

    Morton, Gregory J; Schwartz, Michael W

    2011-04-01

    The regulation of body fat stores and blood glucose levels is critical for survival. This review highlights growing evidence that leptin action in the central nervous system plays a key role in both processes. Investigation into underlying mechanisms has begun to clarify the physiological role of leptin in the control of glucose metabolism and raises interesting new possibilities for the treatment of diabetes and related disorders.

  2. Establishing the relationship between an effective audit committee and infusion of a good control environment

    Directory of Open Access Journals (Sweden)

    Zandile Virtue Dlamini

    2017-12-01

    Full Text Available Audit Committees are a vital component of accountability and good governance for any serious organisation and have progressively been perceived as an integral part of modern control structures and control practices in both the public and private sectors. However, Audit Committees can only discharge such gigantic responsibilities in a conducive environment to provide its effective performance of certain key functions in the areas of oversight of risk management, reporting, and internal controls. Nonetheless, the enablement of such conducive environments has become a challenge to many Audit Committees. It is against this background that this study investigates the relationship between an effective audit committee and infusion of a good control environment. The study used structured and unstructured questions to investigate population comprising standing committee members and Audit Committee members. Thus this study made use of a mixed methodology to collect quantitative data as well as reviewing audit documents, such as, the Audit Committee Charter and minutes of meetings in order to ascertain the environment under which such august practices are performed. The outcome concludes that the Audit Committee which was selected for the study has the good working environment.

  3. Continuous-Time Public Good Contribution Under Uncertainty: A Stochastic Control Approach

    International Nuclear Information System (INIS)

    Ferrari, Giorgio; Riedel, Frank; Steg, Jan-Henrik

    2017-01-01

    In this paper we study continuous-time stochastic control problems with both monotone and classical controls motivated by the so-called public good contribution problem. That is the problem of n economic agents aiming to maximize their expected utility allocating initial wealth over a given time period between private consumption and irreversible contributions to increase the level of some public good. We investigate the corresponding social planner problem and the case of strategic interaction between the agents, i.e. the public good contribution game. We show existence and uniqueness of the social planner’s optimal policy, we characterize it by necessary and sufficient stochastic Kuhn–Tucker conditions and we provide its expression in terms of the unique optional solution of a stochastic backward equation. Similar stochastic first order conditions prove to be very useful for studying any Nash equilibria of the public good contribution game. In the symmetric case they allow us to prove (qualitative) uniqueness of the Nash equilibrium, which we again construct as the unique optional solution of a stochastic backward equation. We finally also provide a detailed analysis of the so-called free rider effect.

  4. Continuous-Time Public Good Contribution Under Uncertainty: A Stochastic Control Approach

    Energy Technology Data Exchange (ETDEWEB)

    Ferrari, Giorgio, E-mail: giorgio.ferrari@uni-bielefeld.de; Riedel, Frank, E-mail: frank.riedel@uni-bielefeld.de; Steg, Jan-Henrik, E-mail: jsteg@uni-bielefeld.de [Bielefeld University, Center for Mathematical Economics (Germany)

    2017-06-15

    In this paper we study continuous-time stochastic control problems with both monotone and classical controls motivated by the so-called public good contribution problem. That is the problem of n economic agents aiming to maximize their expected utility allocating initial wealth over a given time period between private consumption and irreversible contributions to increase the level of some public good. We investigate the corresponding social planner problem and the case of strategic interaction between the agents, i.e. the public good contribution game. We show existence and uniqueness of the social planner’s optimal policy, we characterize it by necessary and sufficient stochastic Kuhn–Tucker conditions and we provide its expression in terms of the unique optional solution of a stochastic backward equation. Similar stochastic first order conditions prove to be very useful for studying any Nash equilibria of the public good contribution game. In the symmetric case they allow us to prove (qualitative) uniqueness of the Nash equilibrium, which we again construct as the unique optional solution of a stochastic backward equation. We finally also provide a detailed analysis of the so-called free rider effect.

  5. Metabolic control of puberty: roles of leptin and kisspeptins.

    Science.gov (United States)

    Sanchez-Garrido, Miguel A; Tena-Sempere, Manuel

    2013-07-01

    This article is part of a Special Issue "Puberty and Adolescence". Reproduction is an energy-demanding function. Accordingly, puberty is metabolically gated, as a means to prevent fertility in conditions of energy insufficiency. In addition, obesity has been shown to impact the timing of puberty and may be among the causes for the earlier trends of pubertal age reported in various countries. The metabolic control of puberty in such a spectrum of situations, ranging from energy deficit to extreme overweight, is the result of the concerted action of different peripheral hormones and central transmitters that sense the metabolic state of the organism and transmit this information to the various elements of the reproductive axis, mainly the GnRH neurons. Among the peripheral signals involved, the adipose hormone, leptin, is known to play an essential role in the regulation of puberty, especially in females. Yet, although it is clear that the effects of leptin on puberty onset are predominantly permissive and mainly conducted at central (hypothalamic) levels, the primary sites and mechanisms of action of leptin within the reproductive brain remain unsolved. In this context, neurons expressing kisspeptins, the products of the Kiss1 gene that have emerged recently as essential upstream regulators of GnRH neurons, operate as key sensors of the metabolic state and funnel of the reproductive effects of leptin. Yet, much debate has arisen recently on whether the putative actions of leptin on the Kiss1 system are actually indirect and/or may primarily target Kiss1-independent pathways, such as those originating from the ventral premmamilary nucleus. Moreover, evidence has been presented for extra-hypothalamic or peripheral actions of leptin, including direct gonadal effects, which may contribute to the metabolic control of reproduction in extreme body weight conditions. In this work, we will critically review the experimental evidence supporting a role of leptin, kisspeptin

  6. Exemption from Regulatory Control of Goods Containing Small Amounts of Radioactive Material

    International Nuclear Information System (INIS)

    2012-01-01

    Small amounts of radioactive material may be added to various goods for functional reasons. Several such items are currently available for either professional or personal use. These include ionization chamber smoke detectors, thoriated-tungsten welding rods, luminous dials, electrical devices and electric discharge lamps. Some of these goods may be intended for particular types of market such as cinemas or other places to which the public may have access, but they are unlikely to be provided directly to members of the public. Other goods may be intended for wide scale use and therefore readily available on the market as consumer products through commercial outlets where personal and household products are normally purchased. Members of the public may be exposed to ionizing radiation as a consequence of activities such as transport, storage, use and disposal of such goods. The IAEA safety standards provide the basic requirements for regulatory control of such goods. The most relevant documents are the Governmental, Legal and Regulatory Framework for Safety and the International Basic Safety Standards (hereafter referred to as the BSS). These requirements include notification of a practice to the regulatory body and authorization of the practice by the regulatory body. Provision is made for the exemption of practices from these and other regulatory requirements based on general criteria given in the BSS or any exemption levels specified by the regulatory body on the basis of these criteria. The BSS, which are jointly sponsored by the IAEA and several other international organizations, apply to all facilities and all activities for peaceful purposes that give rise to exposure to radiation. In the interest of harmonization of approaches among Member States, some guidance on the application of the criteria for exemption has been provided in a number of Safety Guides, e.g. Regulatory Control of Radiation Sources, IAEA Safety Standards Series No. GS-G-1.5 (2004) and the

  7. Healthcare associated infection: good practices, knowledge and the locus of control in heatlhcare professionals.

    Science.gov (United States)

    Taffurelli, Chiara; Sollami, Alfonso; Camera, Carmen; Federa, Francesca; Grandi, Annise; Marino, Marcella; Marrosu, Tiziano; Sarli, Leopoldo

    2017-07-18

      The incidence of Healthcare Associated Infections (HAI) is an important indicator of the quality of care. The behaviors associated with the prevention of infections are not only supported by rational knowledge or motivation, but are mediated by social, emotional and often stereotyped behaviors. The awarness of the good practices related to HAI, may be a factor. Other studies, identify how the perception of the problem in healthcare professionals is often influenced by a tendency towards an external Locus of Control: the patient, the family, the other wards, other care settings. The aim of this study is to investigate the perception of healthcare professionals. In particular they have been measured their  awarness of the good practices, perceptions of the potential contamination level of some commonly used objects, knowledge about the management of invasive devices, Locus of Control.   A cross-sectional correlational design was utilized.  An ad hoc questionnaire was interviewed by 222 health professionals nurses and physicians in a northern hospital of Italy. The percentage of professionals who have attended training courses over the last 5 years was quite high, both for upgrades on HAI (78.7%) and Vascular Catheters (78.8%), while the percentage of professionals who updated on bladder catheterization (59.46%) was lower. The mean  score of good practice awareness towards HAI (5.06), is high. The perception of the potential level of contamination of some devices had a  mean ranging from 4.62 (for the drip) to 5.26 (for the door handle). The average value of the Locus of Control (43.54) indicates that participants demonstrated a value that is midway between External and Internal. The correlation test analysis revealed no significant relationships among professionals'age, knowledge about HAI, or infection related venus catheter. Also, results revealed that there were statistically significant positive relationships between professionals' Good Practices

  8. Sense and nonsense in metabolic control of reproduction.

    Science.gov (United States)

    Schneider, Jill E; Klingerman, Candice M; Abdulhay, Amir

    2012-01-01

    An exciting synergistic interaction occurs among researchers working at the interface of reproductive biology and energy homeostasis. Reproductive biologists benefit from the theories, experimental designs, and methodologies used by experts on energy homeostasis while they bring context and meaning to the study of energy homeostasis. There is a growing recognition that identification of candidate genes for obesity is little more than meaningless reductionism unless those genes and their expression are placed in a developmental, environmental, and evolutionary context. Reproductive biology provides this context because metabolic energy is the most important factor that controls reproductive success and gonadal hormones affect energy intake, storage, and expenditure. Reproductive hormone secretion changes during development, and reproductive success is key to evolutionary adaptation, the process that most likely molded the mechanisms that control energy balance. It is likely that by viewing energy intake, storage, and expenditure in the context of reproductive success, we will gain insight into human obesity, eating disorders, diabetes, and other pathologies related to fuel homeostasis. This review emphasizes the metabolic hypothesis: a sensory system monitors the availability of oxidizable metabolic fuels and orchestrates behavioral motivation to optimize reproductive success in environments where energy availability fluctuates or is unpredictable.

  9. Role of Autophagy in the Control of Body Metabolism

    Directory of Open Access Journals (Sweden)

    Wenying Quan

    2013-03-01

    Full Text Available Autophagy plays a crucial role in the maintenance of cellular nutrient balance and the function of organelles such as mitochondria or the endoplasmic reticulum, which are important in intracellular metabolism, insulin release, and insulin sensitivity. In the insulin-producing pancreatic β-cells, autophagy is important in the maintenance of β-cell mass, structure, and function. Mice with deficiencies in β-cell-specific autophagy show reduced β-cell mass and defects in insulin secretion that lead to hypoinsulinemia and hyperglycemia but not diabetes. However, these mice developed diabetes when bred with ob/ob mice, suggesting that autophagy-deficient β-cells have defects in dealing with the increased metabolic stress imposed by obesity. These results also imply that autophagy deficiency in β-cells could be a factor in the progression from obesity to diabetes. Another important function of autophagy is in hypothalamic neurons for the central control of energy expenditure, appetite, and body weight. In addition, mice with autophagy deficiencies in the target tissues of insulin have yielded diverse phenotypes. Taken together, these results suggest that autophagy is important in the control of whole body energy and nutrient homeostasis, and its dysregulation could play a role in the development of metabolic disorders and diabetes.

  10. Competitiveness, export control and export promotion of dual-use goods. European and German balancing exercises

    International Nuclear Information System (INIS)

    Feldmann, Ulrike

    2014-01-01

    The EU Commission Communication of 24 April 2014 to the Council and the European Parliament ''The review of export control policy: Ensuring Security and Competitiveness in a changing world'' as well as the increasingly number of inquiries and applications to the German Federal Government (e.g. the rejection of Hermes guarantees and state funding of nuclear export and termination of bilateral cooperation in the field of nuclear technologies) once again reason to discuss the current tension between the principle of free movement of goods, competitiveness and export promotion on the one hand and the export control on the other.

  11. Metabolic control of vesicular glutamate transport and release.

    Science.gov (United States)

    Juge, Narinobu; Gray, John A; Omote, Hiroshi; Miyaji, Takaaki; Inoue, Tsuyoshi; Hara, Chiaki; Uneyama, Hisayuki; Edwards, Robert H; Nicoll, Roger A; Moriyama, Yoshinori

    2010-10-06

    Fasting has been used to control epilepsy since antiquity, but the mechanism of coupling between metabolic state and excitatory neurotransmission remains unknown. Previous work has shown that the vesicular glutamate transporters (VGLUTs) required for exocytotic release of glutamate undergo an unusual form of regulation by Cl(-). Using functional reconstitution of the purified VGLUTs into proteoliposomes, we now show that Cl(-) acts as an allosteric activator, and the ketone bodies that increase with fasting inhibit glutamate release by competing with Cl(-) at the site of allosteric regulation. Consistent with these observations, acetoacetate reduced quantal size at hippocampal synapses and suppresses glutamate release and seizures evoked with 4-aminopyridine in the brain. The results indicate an unsuspected link between metabolic state and excitatory neurotransmission through anion-dependent regulation of VGLUT activity. Copyright © 2010 Elsevier Inc. All rights reserved.

  12. The insect ecdysone receptor is a good potential target for RNAi-based pest control.

    Science.gov (United States)

    Yu, Rong; Xu, Xinping; Liang, Yongkang; Tian, Honggang; Pan, Zhanqing; Jin, Shouheng; Wang, Na; Zhang, Wenqing

    2014-01-01

    RNA interference (RNAi) has great potential for use in insect pest control. However, some significant challenges must be overcome before RNAi-based pest control can become a reality. One challenge is the proper selection of a good target gene for RNAi. Here, we report that the insect ecdysone receptor (EcR) is a good potential target for RNAi-based pest control in the brown planthopper Nilaparvata lugens, a serious insect pest of rice plants. We demonstrated that the use of a 360 bp fragment (NlEcR-c) that is common between NlEcR-A and NlEcR-B for feeding RNAi experiments significantly decreased the relative mRNA expression levels of NlEcR compared with those in the dsGFP control. Feeding RNAi also resulted in a significant reduction in the number of offspring per pair of N. lugens. Consequently, a transgenic rice line expressing NlEcR dsRNA was constructed by Agrobacterium- mediated transformation. The results of qRT-PCR showed that the total copy number of the target gene in all transgenic rice lines was 2. Northern blot analysis showed that the small RNA of the hairpin dsNlEcR-c was successfully expressed in the transgenic rice lines. After newly hatched nymphs of N. lugens fed on the transgenic rice lines, effective RNAi was observed. The NlEcR expression levels in all lines examined were decreased significantly compared with the control. In all lines, the survival rate of the nymphs was nearly 90%, and the average number of offspring per pair in the treated groups was significantly less than that observed in the control, with a decrease of 44.18-66.27%. These findings support an RNAi-based pest control strategy and are also important for the management of rice insect pests.

  13. Brain Ceramide Metabolism in the Control of Energy Balance

    Directory of Open Access Journals (Sweden)

    Céline Cruciani-Guglielmacci

    2017-10-01

    Full Text Available The regulation of energy balance by the central nervous system (CNS is a key actor of energy homeostasis in mammals, and deregulations of the fine mechanisms of nutrient sensing in the brain could lead to several metabolic diseases such as obesity and type 2 diabetes (T2D. Indeed, while neuronal activity primarily relies on glucose (lactate, pyruvate, the brain expresses at high level enzymes responsible for the transport, utilization and storage of lipids. It has been demonstrated that discrete neuronal networks in the hypothalamus have the ability to detect variation of circulating long chain fatty acids (FA to regulate food intake and peripheral glucose metabolism. During a chronic lipid excess situation, this physiological lipid sensing is impaired contributing to type 2 diabetes in predisposed subjects. Recently, different studies suggested that ceramides levels could be involved in the regulation of energy balance in both hypothalamic and extra-hypothalamic areas. Moreover, under lipotoxic conditions, these ceramides could play a role in the dysregulation of glucose homeostasis. In this review we aimed at describing the potential role of ceramides metabolism in the brain in the physiological and pathophysiological control of energy balance.

  14. NAMPT and NAMPT-controlled NAD Metabolism in Vascular Repair.

    Science.gov (United States)

    Wang, Pei; Li, Wen-Lin; Liu, Jian-Min; Miao, Chao-Yu

    2016-06-01

    Vascular repair plays important roles in postischemic remodeling and rehabilitation in cardiovascular and cerebrovascular disease, such as stroke and myocardial infarction. Nicotinamide adenine dinucleotide (NAD), a well-known coenzyme involved in electron transport chain for generation of adenosine triphosphate, has emerged as an important controller regulating various biological signaling pathways. Nicotinamide phosphoribosyltransferase (NAMPT) is the rate-limiting enzyme for NAD biosynthesis in mammals. NAMPT may also act in a nonenzymatic manner, presumably mediated by unknown receptor(s). Rapidly accumulating data in the past decade show that NAMPT and NAMPT-controlled NAD metabolism regulate fundamental biological functions in endothelial cells, vascular smooth muscle cells, and endothelial progenitor cells. The NAD-consuming proteins, including sirtuins, poly-ADP-ribose polymerases (PARPs), and CD38, may contribute to the regulatory effects of NAMPT-NAD axis in these cells and vascular repair. This review discusses the current data regarding NAMPT and NAMPT-controlled NAD metabolism in vascular repair and the clinical potential translational application of NAMPT-related products in treatment of cardiovascular and cerebrovascular disease.

  15. Metabolic control of muscle blood flow during exercise in humans

    DEFF Research Database (Denmark)

    Boushel, Robert Christopher

    2003-01-01

    that combined blockade of NOS and PGI2, and NOS and cytochrome P450, both attenuate exercise-induced hyperemia in humans. Combined vasodilator blockade studies offer the potential to uncover important interactions and compensatory vasodilator responses. The signaling pathways that link metabolic events evoked...... to exert control of muscle vasodilation. Adenosine, nitric oxide (NO), prostacyclin (PGI2), and endothelial-derived hyperpolarization factor (EDHF) are possible mediators of muscle vasodilation during exercise. In humans, adenosine has been shown to contribute to functional hyperemia as blood flow...... by muscle contraction to vasodilatory signals in the local vascular bed remains an important area of study....

  16. 78 FR 64425 - Current Good Manufacturing Practice and Hazard Analysis and Risk-Based Preventive Controls for...

    Science.gov (United States)

    2013-10-29

    ..., 507, and 579 [Docket No. FDA-2011-N-0922] Current Good Manufacturing Practice and Hazard Analysis and... requirements for current good manufacturing practice and hazard analysis and risk-based preventive controls for..., packing, or holding of animal food in two ways. First, it would create new current good manufacturing...

  17. Metabolism

    Science.gov (United States)

    ... Are More Common in People With Type 1 Diabetes Metabolic Syndrome Your Child's Weight Healthy Eating Endocrine System Blood Test: Basic Metabolic Panel (BMP) Activity: Endocrine System Growth Disorders Diabetes Center Thyroid Disorders Your Endocrine System Movie: Endocrine ...

  18. Exercise, Obesity and CNS Control of Metabolic Homeostasis: A Review

    Science.gov (United States)

    Smith, John K.

    2018-01-01

    This review details the manner in which the central nervous system regulates metabolic homeostasis in normal weight and obese rodents and humans. It includes a review of the homeostatic contributions of neurons located in the hypothalamus, the midbrain and limbic structures, the pons and the medullary area postrema, nucleus tractus solitarius, and vagus nucleus, and details how these brain regions respond to circulating levels of orexigenic hormones, such as ghrelin, and anorexigenic hormones, such as glucagon-like peptide 1 and leptin. It provides an insight as to how high intensity exercise may improve homeostatic control in overweight and obese subjects. Finally, it provides suggestions as to how further progress can be made in controlling the current pandemic of obesity and diabetes.

  19. Space Station CMIF extended duration metabolic control test

    Science.gov (United States)

    Schunk, Richard G.; Bagdigian, Robert M.; Carrasquillo, Robyn L.; Ogle, Kathryn Y.; Wieland, Paul O.

    1989-01-01

    The Space Station Extended Duration Metabolic Control Test (EMCT) was conducted at the MSFC Core Module Integration Facility. The primary objective of the EMCT was to gather performance data from a partially-closed regenerative Environmental Control and Life Support (ECLS) system functioning under steady-state conditions. Included is a description of the EMCT configuration, a summary of events, a discussion of anomalies that occurred during the test, and detailed results and analysis from individual measurements of water and gas samples taken during the test. A comparison of the physical, chemical, and microbiological methods used in the post test laboratory analyses of the water samples is included. The preprototype ECLS hardware used in the test, providing an overall process description and theory of operation for each hardware item. Analytical results pertaining to a system level mass balance and selected system power estimates are also included.

  20. Pyruvate Kinase Triggers a Metabolic Feedback Loop that Controls Redox Metabolism in Respiring Cells

    NARCIS (Netherlands)

    Grüning, N.M.; Rinnerthaler, M.; Bluemlein, K.; Mulleder, M.; Wamelink, M.M.C.; Lehrach, H.; Jakobs, C.A.J.M.; Breitenbach, M.; Ralser, M.

    2011-01-01

    In proliferating cells, a transition from aerobic to anaerobic metabolism is known as the Warburg effect, whose reversal inhibits cancer cell proliferation. Studying its regulator pyruvate kinase (PYK) in yeast, we discovered that central metabolism is self-adapting to synchronize redox metabolism

  1. FGF-dependent metabolic control of vascular development

    Science.gov (United States)

    Yu, Pengchun; Alves, Tiago C.; Fang, Jennifer S.; Xie, Yi; Zhu, Jie; Chen, Zehua; De Smet, Frederik; Zhang, Jiasheng; Jin, Suk-Won; Sun, Lele; Sun, Hongye; Kibbey, Richard G.; Hirschi, Karen K.; Hay, Nissim; Carmeliet, Peter; Chittenden, Thomas W.; Eichmann, Anne; Potente, Michael; Simons, Michael

    2017-01-01

    Blood and lymphatic vasculatures are intimately involved in tissue oxygenation and fluid homeostasis maintenance. Assembly of these vascular networks involves sprouting, migration and proliferation of endothelial cells. Recent studies have suggested that changes in cellular metabolism are of importance to these processes1. While much is known about vascular endothelial growth factor (VEGF)-dependent regulation of vascular development and metabolism2,3, little is understood about the role of fibroblast growth factors (FGFs) in this context4. Here we identify FGF receptor (FGFR) signaling as a critical regulator of vascular development. This is achieved by FGF-dependent control of c-MYC (MYC) expression that, in turn, regulates expression of the glycolytic enzyme hexokinase 2 (HK2). A decrease in HK2 levels in the absence of FGF signaling inputs results in decreased glycolysis leading to impaired endothelial cell proliferation and migration. Pan-endothelial- and lymphatic-specific Hk2 knockouts phenocopy blood and/or lymphatic vascular defects seen in Fgfr1/r3 double mutant mice while HK2 overexpression partially rescues the defects caused by suppression of FGF signaling. Thus, FGF-dependent regulation of endothelial glycolysis is a pivotal process in developmental and adult vascular growth and development. PMID:28467822

  2. Modular glovebox connector and associated good practices for control of radioactive and chemically toxic materials

    International Nuclear Information System (INIS)

    Hoover, M.D.; Mewhinney, C.J.; Newton, G.J.

    1999-01-01

    Design and associated good practices are described for a modular glovebox connector to improve control of radioactive and chemically toxic materials. The connector consists of an anodized aluminum circular port with a mating spacer, gaskets, and retaining rings for joining two parallel ends of commercially available or custom-manufactured glovebox enclosures. Use of the connector allows multiple gloveboxes to be quickly assembled or reconfigured in functional units. Connector dimensions can be scaled to meet operational requirements for access between gloveboxes. Options for construction materials are discussed, along with recommendations for installation of the connector in new or retrofitted systems. Associated good practices include application of surface coatings and caulking, use of disposable glovebags, and proper selection and protection of gasket and glove materials. Use of the connector at an inhalation toxicology research facility has reduced the time and expense required to reconfigure equipment for changing operational requirements, the dispersion of contamination during reconfigurations, and the need for decommissioning and disposal of contaminated enclosures

  3. The Sexual Advantage of Looking, Smelling, and Tasting Good: The Metabolic Network that Produces Signals for Pollinators.

    Science.gov (United States)

    Borghi, Monica; Fernie, Alisdair R; Schiestl, Florian P; Bouwmeester, Harro J

    2017-04-01

    A striking feature of the angiosperms that use animals as pollen carriers to sexually reproduce is the great diversity of their flowers with regard to morphology and traits such as color, odor, and nectar. These traits are underpinned by the synthesis of secondary metabolites such as pigments and volatiles, as well as carbohydrates and amino acids, which are used by plants to lure and reward animal pollinators. We review here the knowledge of the metabolic network that supports the biosynthesis of these compounds and the behavioral responses that these molecules elicit in the animal pollinators. Such knowledge provides us with a deeper insight into the ecology and evolution of plant-pollinator interactions, and should help us to better manage these ecologically essential interactions in agricultural ecosystems. Copyright © 2016 Elsevier Ltd. All rights reserved.

  4. Effect of metabolic control on parathyroid hormone secretion in diabetic patients

    Directory of Open Access Journals (Sweden)

    Paula F.J.A.

    2001-01-01

    Full Text Available The metabolic derangement caused by diabetes mellitus may potentially affect bone mineral metabolism. In the present study we evaluated the effect of diabetes metabolic control on parathyroid hormone (PTH secretion during stimulation with EDTA infusion. The study was conducted on 24 individuals, 8 of them normal subjects (group N: glycated hemoglobin - HbA1C = 4.2 ± 0.2%; range = 3.5-5.0%, 8 patients with good and regular metabolic control (group G-R: HbA1C = 7.3 ± 0.4%; range = 6.0-8.5%, and 8 patients with poor metabolic control (group P: HbA1C = 12.5 ± 1.0%; range: 10.0-18.8%. Blood samples were collected at 10-min intervals throughout the study (a basal period of 30 min and a 2-h period of EDTA infusion, 30 mg/kg body weight and used for the determination of ionized calcium, magnesium, glucose and intact PTH. Basal ionized calcium levels were slightly lower in group P (1.19 ± 0.01 mmol/l than in group N (1.21 ± 0.01 mmol/l and group G-R (1.22 ± 0.01 mmol/l. After EDTA infusion, the three groups presented a significant fall in calcium, but with no significant difference among them at any time. Basal magnesium levels and levels determined during EDTA infusion were significantly lower (P<0.01 in group P than in group N. The induction of hypocalcemia caused an elevation in PTH which was similar in groups N and G-R but significantly higher than in group P throughout the infusion period (+110 min, N = 11.9 ± 2.1 vs G-R = 13.7 ± 1.6 vs P = 7.5 ± 0.7 pmol/l; P<0.05 for P vs N and G-R. The present results show that PTH secretion is impaired in patients with poorly controlled diabetes.

  5. Metabolism

    Science.gov (United States)

    ... lin), which signals cells to increase their anabolic activities. Metabolism is a complicated chemical process, so it's not ... how those enzymes or hormones work. When the metabolism of body chemicals is ... Hyperthyroidism (pronounced: hi-per-THIGH-roy-dih-zum). Hyperthyroidism ...

  6. 78 FR 24691 - Current Good Manufacturing Practice and Hazard Analysis and Risk-Based Preventive Controls for...

    Science.gov (United States)

    2013-04-26

    ... comments should be identified with the title ``Current Good Manufacturing Practice and Hazard Analysis and..., 114, 117, 120, 123, 129, 179, and 211 [Docket No. FDA-2011-N-0920] RIN 0910-AG36 Current Good Manufacturing Practice and Hazard Analysis and Risk- Based Preventive Controls for Human Food; Extension of...

  7. Perspectives in metabolic engineering: understanding cellular regulation towards the control of metabolic routes.

    Science.gov (United States)

    Zadran, Sohila; Levine, Raphael D

    2013-01-01

    Metabolic engineering seeks to redirect metabolic pathways through the modification of specific biochemical reactions or the introduction of new ones with the use of recombinant technology. Many of the chemicals synthesized via introduction of product-specific enzymes or the reconstruction of entire metabolic pathways into engineered hosts that can sustain production and can synthesize high yields of the desired product as yields of natural product-derived compounds are frequently low, and chemical processes can be both energy and material expensive; current endeavors have focused on using biologically derived processes as alternatives to chemical synthesis. Such economically favorable manufacturing processes pursue goals related to sustainable development and "green chemistry". Metabolic engineering is a multidisciplinary approach, involving chemical engineering, molecular biology, biochemistry, and analytical chemistry. Recent advances in molecular biology, genome-scale models, theoretical understanding, and kinetic modeling has increased interest in using metabolic engineering to redirect metabolic fluxes for industrial and therapeutic purposes. The use of metabolic engineering has increased the productivity of industrially pertinent small molecules, alcohol-based biofuels, and biodiesel. Here, we highlight developments in the practical and theoretical strategies and technologies available for the metabolic engineering of simple systems and address current limitations.

  8. Improved Metabolic Control in Diabetes, HSP60, and Proinflammatory Mediators

    Directory of Open Access Journals (Sweden)

    Claudio Blasi

    2012-01-01

    Full Text Available The diabetes-atherosclerosis relationship remains to be fully defined. Repeated prolonged hyperglycemia, increased ROS production and endothelial dysfunction are important factors. One theory is that increased blood levels of heat shock protein (HSP60 are proinflammatory, through activation of innate immunity, and contribute to the progression of vascular disease. It was hypothesized that improvement of diabetes control in patients presenting with metabolic syndrome would lower HSP60, and anti-HSP60 antibody levels and decrease inflammatory markers. Paired sera of 17 Italian patients, before and after intensive treatment, were assayed for cytokines, HSP60 and anti-HSP60 antibodies. As expected, intensive treatment was associated with a decrease in HgbA1C (P<0.001 and BMI (P<0.001. After treatment, there was a significant decrease in IL-6 (P<0.05. HSP60 levels were before treatment −6.9+1.9, after treatment −7.1+2.0 ng/mL (P=ns. Overall HSP60 concentrations were lower than published reports. Anti-HSP60 antibody titers were high and did not decrease with treatment. In conclusion, improvement of diabetic control did not alter HSP60 concentrations or antiHSP60 antibody titers, but led to a reduction of IL-6 levels.

  9. Relationship between patients' perception of the importance of diabetes and metabolic control and pursuing chronic complications of disease

    Directory of Open Access Journals (Sweden)

    Mohammad Ebrahim Khamseh

    2011-04-01

    Full Text Available Introduction: Type II diabetes is a metabolic disorder. Environmental factors and patient awareness have major roles on chronic complications. The purpose of this study was to determine the association of patients' perception of t the importance of diabetes and metabolic- control and pursuing of chronic complications. Material and Methods: 194 patients with diabetes enrolled from diabetes clinic of Institute Endocrinology & Metabolism in a cross-sectional study, from February to March 2010. Data were collected using a questionnaire to assess the personal demographics, individual approach in pursuit of complications, and glycemic control, as well as patient perception and attitude toward the importance of disease process and follow-up. Level of perceptions was determined as well, moderate and weak. Results: Out of 194 patients, 77(39.7% were male and 117(60.3% female. Mean age was 52.18±10.17years. 69.2% did not know what the glycosylated hemoglobin was. In 71.4%, willing to participate in decisions making on medical treatment was good and they knew that with initiation of insulin therapy, they would have better metabolic control. 68.9% of patients had regular follow-up for eye complications, and 51% for cardiac complications. Follow-up for diabetic foot complication was poor. Patients with good perception had regular follow-up regarding cardiac, eye and renal complications. Conclusion: These results indicate that better perception of diabetic patients might improve their compliance for regular follow- up regarding the pursuit of chronic complications, especially cardiac, eye and renal problems. Although, the metabolic- control of patients had not the association with patient perception about the importance of diabetes

  10. Adipokines, inflammatory mediators, and insulin-resistance parameters may not be good markers of metabolic syndrome after liver transplant.

    Science.gov (United States)

    Anastácio, Lucilene Rezende; de Oliveira, Marina Chaves; Diniz, Kiara Gonçalves; Ferreira, Adaliene Matos Versiane; Lima, Agnaldo Soares; Correia, Maria Isabel Toulson Davisson; Vilela, Eduardo Garcia

    2016-09-01

    The role of adipokines in liver transplantation (LTx) recipients who have metabolic syndrome (MetS) has seldom been assessed. The aim of this study was to investigate the concentrations of adipokines, inflammatory mediators, and insulin-resistance markers in liver recipients with MetS and its components. Serum samples from 34 patients (55.9% male; 54.9 ± 13.9 y; 7.7 ± 2.9 y after LTx; 50% presented with MetS) were assessed for adiponectin, resistin, tumor necrosis factor (TNF)-α, monocyte chemoattractant protein (MCP)-1, interleukin (IL)-6, C-reactive protein (CRP), homeostatic model assessment-insulin resistance (HOMA-IR) and free fatty acid (FFA) levels. The dosages were uni- and multivariate analyzed to cover MetS (using the Harmonizing MetS criteria), its components, and dietary intake. A higher concentration of adiponectin (P < 0.05) was observed among patients with MetS (5.2 ± 3.2 μg/mL) compared with those without MetS (3.2 ± 1.2 μg/mL), as well as those with MetS components versus those without them: abdominal obesity (4.6 ± 2.6 μg/mL versus 2.6 ± 0.6 μg/mL), high triacylglycerols (TGs; 5.6 ± 3.1 μg/mL versus 3 ± 0.9 μg/mL) and low high-density lipoprotein (HDL; 6.1 ± 2.7 μg/mL versus 3.3 ± 1.9 μg/mL). Increased TNF-α and HOMA-IR values were seen in patients with abdominal obesity. Patients with high TGs also had greater FFA values. Independent predictors for adiponectin were waist-to-hip ratio, low HDL and high TGs. High TGs and fasting blood glucose were independent predictors for HOMA-IR. Independent predictors could not be identified for CRP, TNF-α, MCP-1, IL-6, or FFA. MetS and its components are related to an increased HOMA-IR concentration and FFA. Adiponectin, resistin, and inflammatory markers, such as TNF-α, IL-6, MCP-1, and CRP, were not associated with MetS in this sample of post-LTx patients. Copyright © 2016 Elsevier Inc. All rights reserved.

  11. Achieving the same for less: improving mood depletes blood glucose for people with poor (but not good) emotion control.

    Science.gov (United States)

    Niven, Karen; Totterdell, Peter; Miles, Eleanor; Webb, Thomas L; Sheeran, Paschal

    2013-01-01

    Previous studies have found that acts of self-control like emotion regulation deplete blood glucose levels. The present experiment investigated the hypothesis that the extent to which people's blood glucose levels decline during emotion regulation attempts is influenced by whether they believe themselves to be good or poor at emotion control. We found that although good and poor emotion regulators were equally able to achieve positive and negative moods, the blood glucose of poor emotion regulators was reduced after performing an affect-improving task, whereas the blood glucose of good emotion regulators remained unchanged. As evidence suggests that glucose is a limited energy resource upon which self-control relies, the implication is that good emotion regulators are able to achieve the same positive mood with less cost to their self-regulatory resource. Thus, depletion may not be an inevitable consequence of engaging in emotion regulation.

  12. Self-Efficacy, Self-Care, and Metabolic Control in Persons with Type 2, Diet and Exercised Controlled Diabetes

    National Research Council Canada - National Science Library

    Randall, Lisa

    1998-01-01

    ... (Diabetes control and Complications Trial, 1993). Nurses' understanding of diabetes management coupled with a holistic view of person makes them the optimal professionals to facilitate patient movement toward tight metabolic control...

  13. Integration of Environmental and Developmental (or Metabolic) Control of Seed Mass by Sugar and Ethylene Metabolisms in Arabidopsis.

    Science.gov (United States)

    Meng, Lai-Sheng; Xu, Meng-Ke; Wan, Wen; Wang, Jing-Yi

    2018-04-04

    In higher plants, seed mass is an important to evolutionary fitness. In this context, seedling establishment positively correlates with seed mass under conditions of environmental stress. Thus, seed mass constitutes an important agricultural trait. Here, we show loss-of-function of YODA (YDA), a MAPKK Kinase, and decreased seed mass, which leads to susceptibility to drought. Furthermore, we demonstrate that yda disrupts sugar metabolisms but not the gaseous plant hormone, ethylene. Our data suggest that the transcription factor EIN3 (ETHYLENE-INSENSITIVE3), integral to both sugar and ethylene metabolisms, physically interacts with YDA. Further, ein3-1 mutants exhibited increased seed mass. Genetic analysis indicated that YDA and EIN3 were integral to a sugar-mediated metabolism cascade which regulates seed mass by maternally controlling embryo size. It is well established that ethylene metabolism leads to the suppression of drought tolerance by the EIN3 mediated inhibition of CBF1, a transcription factor required for the expression genes of abiotic stress. Our findings help guide the synthesis of a model predicting how sugar/ethylene metabolisms and environmental stress are integrated at EIN3 to control both the establishment of drought tolerance and the production of seed mass. Collectively, these insights into the molecular mechanism underpinning the regulation of plant seed size may aid prospective breeding or design strategies to increase crop yield.

  14. BEYOND GLYCEMIC CONTROL IN DIABETES MELLITUS: EFFECTS OF INCRETIN-BASED THERAPY ON BONE METABOLISM

    Directory of Open Access Journals (Sweden)

    ELENA eCECCARELLI

    2013-06-01

    Full Text Available Diabetes mellitus (DM and osteoporosis (OP are common disorders with a significant health burden, and an increase in fracture risk has been described both in type 1 (T1DM and in type 2 (T2DM diabetes. The pathogenic mechanisms of impaired skeletal strength in diabetes remain to be clarified in details and they are only in part reflected by a variation in bone mineral density (BMD. In T2DM, the occurrence of low bone turnover together with a decreased osteoblast activity and compromised bone quality has been shown. Of note, some antidiabetic drugs (e.g. tiazolidinediones, insulin may deeply affect bone metabolism. In addition, the recently introduced class of incretin-based drugs (i.e. GLP-1 receptor agonists and DPP-4 inhibitors is expected to exert potentially beneficial effects on bone health, possibly due to a bone anabolic activity of GLP-1, that can be either direct or indirect through the involvement of thyroid C cells.Here we will review the established as well as the putative effects of incretin hormones and of incretin-based drugs on bone metabolism, both in preclinical models and in man, taking into account that such therapeutic strategy may be effective not only to achieve a good glycemic control, but also to improve bone health in diabetic patients.

  15. Regular Workflow of the Customs on the Supervision and Control over the Import & Export Goods

    Institute of Scientific and Technical Information of China (English)

    2009-01-01

    @@ Declaration & Management Article 25 of Customs Law prescribes that paper declaration form and electronic declaration form must be adopted in the Customs declaration formalities for the import & export goods.

  16. Factors associated with good TB infection control practices among primary healthcare workers in the Free State Province, South Africa.

    Science.gov (United States)

    Engelbrecht, Michelle; Janse van Rensburg, André; Kigozi, Gladys; van Rensburg, Hcj Dingie

    2016-11-04

    Despite the availability of TB infection control guidelines, and good levels of healthcare worker knowledge about infection control, often these measures are not well implemented. This study sought to determine the factors associated with healthcare workers' good TB infection control practices in primary health care facilities in the Free State Province, South Africa. A cross-sectional self-administered survey among nurses (n = 202) and facility-based community healthcare workers (n = 34) as well as facility observations were undertaken at all 41 primary health care facilities in a selected district of the Free State Province. The majority of respondents were female (n = 200; 87.7 %) and the average age was 44.19 years (standard deviation ±10.82). Good levels of knowledge were recorded, with 42.8 % (n = 101) having an average score (i.e. 65-79 %) and 31.8 % (n = 75) a good score (i.e. ≥ 80 %). Most respondents (n = 189; 80.4 %) had positive attitudes towards TB infection control practices (i.e. ≥ 80 %). While good TB infection control practices were reported by 72.9 % (n = 161) of the respondents (i.e. ≥75 %), observations revealed this to not necessarily be the case. For every unit increase in attitudes, good practices increased 1.090 times (CI:1.016-1.169). Respondents with high levels of knowledge (≥80 %) were 4.029 (CI: 1.550-10.469) times more likely to have good practices when compared to respondents with poor levels of knowledge (control were the main factors associated with good infection control practices. Although many respondents reported good infection control practices - which was somewhat countered by the observations - there are areas that require attention, particularly those related to administrative controls and the use of personal protective equipment.

  17. Synergizing metabolic flux analysis and nucleotide sugar metabolism to understand the control of glycosylation of recombinant protein in CHO cells

    LENUS (Irish Health Repository)

    Burleigh, Susan C

    2011-10-18

    Abstract Background The glycosylation of recombinant proteins can be altered by a range of parameters including cellular metabolism, metabolic flux and the efficiency of the glycosylation process. We present an experimental set-up that allows determination of these key processes associated with the control of N-linked glycosylation of recombinant proteins. Results Chinese hamster ovary cells (CHO) were cultivated in shake flasks at 0 mM glutamine and displayed a reduced growth rate, glucose metabolism and a slower decrease in pH, when compared to other glutamine-supplemented cultures. The N-linked glycosylation of recombinant human chorionic gonadotrophin (HCG) was also altered under these conditions; the sialylation, fucosylation and antennarity decreased, while the proportion of neutral structures increased. A continuous culture set-up was subsequently used to understand the control of HCG glycosylation in the presence of varied glutamine concentrations; when glycolytic flux was reduced in the absence of glutamine, the glycosylation changes that were observed in shake flask culture were similarly detected. The intracellular content of UDP-GlcNAc was also reduced, which correlated with a decrease in sialylation and antennarity of the N-linked glycans attached to HCG. Conclusions The use of metabolic flux analysis illustrated a case of steady state multiplicity, where use of the same operating conditions at each steady state resulted in altered flux through glycolysis and the TCA cycle. This study clearly demonstrated that the control of glycoprotein microheterogeneity may be examined by use of a continuous culture system, metabolic flux analysis and assay of intracellular nucleotides. This system advances our knowledge of the relationship between metabolic flux and the glycosylation of biotherapeutics in CHO cells and will be of benefit to the bioprocessing industry.

  18. Nucleotide Metabolism and its Control in Lactic Acid Bacteria

    DEFF Research Database (Denmark)

    Kilstrup, Mogens; Hammer, Karin; Jensen, Peter Ruhdal

    2005-01-01

    Most metabolic reactions are connected through either their utilization of nucleotides or their utilization of nucleotides or their regulation by these metabolites. In this review the biosynthetic pathways for pyrimidine and purine metabolism in lactic acid bacteria are described including...... the interconversion pathways, the formation of deoxyribonucleotides and the salvage pathways for use of exogenous precursors. The data for the enzymatic and the genetic regulation of these pathways are reviewed, as well as the gene organizations in different lactic acid bacteria. Mutant phenotypes and methods...... for manipulation of nucleotide pools are also discussed. Our aim is to provide an overview of the physiology and genetics of nucleotide metabolism and its regulation that will facilitate the interpretation of data arising from genetics, metabolomics, proteomics, and transcriptomics in lactic acid bacteria....

  19. Metabolic Engineering of Chemical Defence Pathways in Plant Disease Control

    DEFF Research Database (Denmark)

    Rook, Frederik

    2016-01-01

    on each topic. The chapter reviews the some of the scientific and technical challenges in metabolic engineering and the new possibilities emerging from recent technological developments. It concludes by discussing the outlook for bioengineered chemical defences as part of crop protection strategies, also...... with antimicrobial properties for use in crop protection. It presents an overview of the metabolic engineering efforts made in the area of plant chemical defence. For in-depth information on the characteristics of a specific class of chemical defence compounds, the reader is referred to the specialized reviews...

  20. Control of alanine metabolism in rat liver by transport processes or cellular metabolism.

    OpenAIRE

    Fafournoux, P; Rémésy, C; Demigné, C

    1983-01-01

    1. Factors governing hepatic utilization of alanine were studied in vivo and in vitro in rats adapted to increasing dietary protein. 2. Hepatic alanine utilization was enhanced 5-fold with a 90%-casein diet, compared with a 13%-casein diet. The increased uptake resulted from enhanced fractional extraction in the presence of high concentrations of alanine in the portal vein. 3. The increase in alanine metabolism on high-protein diets was associated with an increase in alanine aminotransferase ...

  1. Self-Efficacy, Self-Care, and Metabolic Control in Persons with Type 2, Diet and Exercised Controlled Diabetes

    National Research Council Canada - National Science Library

    Randall, Lisa

    1998-01-01

    .... psychological determinants of self-care and metabolic control must be explored. Self-efficacy (Bandura, 1977) has demonstrated its importance in behavioral modification but has been minimally investigated in diabetes...

  2. Predictive Effects of Good Self-Control and Poor Regulation on Alcohol-Related Outcomes: Do Protective Behavioral Strategies Mediate?

    Science.gov (United States)

    Pearson, Matthew R.; Kite, Benjamin A.; Henson, James M.

    2016-01-01

    In the present study, we examined whether use of protective behavioral strategies mediated the relationship between self-control constructs and alcohol-related outcomes. According to the two-mode model of self-control, good self-control (planfulness; measured with Future Time Perspective, Problem Solving, and Self-Reinforcement) and poor regulation (impulsivity; measured with Present Time Perspective, Poor Delay of Gratification, Distractibility) are theorized to be relatively independent constructs rather than opposite ends of a single continuum. The analytic sample consisted of 278 college student drinkers (68% women) who responded to a battery of surveys at a single time point. Using a structural equation model based on the two-mode model of self-control, we found that good self-control predicted increased use of three types of protective behavioral strategies (Manner of Drinking, Limiting/Stopping Drinking, and Serious Harm Reduction). Poor regulation was unrelated to use of protective behavioral strategies, but had direct effects on alcohol use and alcohol problems. Further, protective behavioral strategies mediated the relationship between good self-control and alcohol use. The clinical implications of these findings are discussed. PMID:22663345

  3. Mitofusin 2 as a driver that controls energy metabolism and insulin signaling.

    Science.gov (United States)

    Zorzano, Antonio; Hernández-Alvarez, María Isabel; Sebastián, David; Muñoz, Juan Pablo

    2015-04-20

    Mitochondrial dynamics is a complex process that impacts on mitochondrial biology. Recent evidence indicates that proteins participating in mitochondrial dynamics have additional cellular roles. Mitofusin 2 (Mfn2) is a potent modulator of mitochondrial metabolism with an impact on energy metabolism in muscle, liver, and hypothalamic neurons. In addition, Mfn2 is subjected to tight regulation. Hence, factors such as proinflammatory cytokines, lipid availability, or glucocorticoids block its expression, whereas exercise and increased energy expenditure promote its upregulation. Importantly, Mfn2 controls cell metabolism and insulin signaling by limiting reactive oxygen species production and by modulation of endoplasmic reticulum stress. In this connection, it is critical to understand precisely the molecular mechanisms involved in the global actions of Mfn2. Future directions should concentrate into the analysis of those mechanisms, and to fully demonstrate that Mfn2 represents a cellular hub that senses the metabolic and hormonal milieu and drives the control of metabolic homeostasis.

  4. Non-clinical studies in the process of new drug development - Part II: Good laboratory practice, metabolism, pharmacokinetics, safety and dose translation to clinical studies.

    Science.gov (United States)

    Andrade, E L; Bento, A F; Cavalli, J; Oliveira, S K; Schwanke, R C; Siqueira, J M; Freitas, C S; Marcon, R; Calixto, J B

    2016-12-12

    The process of drug development involves non-clinical and clinical studies. Non-clinical studies are conducted using different protocols including animal studies, which mostly follow the Good Laboratory Practice (GLP) regulations. During the early pre-clinical development process, also known as Go/No-Go decision, a drug candidate needs to pass through several steps, such as determination of drug availability (studies on pharmacokinetics), absorption, distribution, metabolism and elimination (ADME) and preliminary studies that aim to investigate the candidate safety including genotoxicity, mutagenicity, safety pharmacology and general toxicology. These preliminary studies generally do not need to comply with GLP regulations. These studies aim at investigating the drug safety to obtain the first information about its tolerability in different systems that are relevant for further decisions. There are, however, other studies that should be performed according to GLP standards and are mandatory for the safe exposure to humans, such as repeated dose toxicity, genotoxicity and safety pharmacology. These studies must be conducted before the Investigational New Drug (IND) application. The package of non-clinical studies should cover all information needed for the safe transposition of drugs from animals to humans, generally based on the non-observed adverse effect level (NOAEL) obtained from general toxicity studies. After IND approval, other GLP experiments for the evaluation of chronic toxicity, reproductive and developmental toxicity, carcinogenicity and genotoxicity, are carried out during the clinical phase of development. However, the necessity of performing such studies depends on the new drug clinical application purpose.

  5. Exercise, Obesity and CNS Control of Metabolic Homeostasis: A Review

    OpenAIRE

    John K. Smith

    2018-01-01

    This review details the manner in which the central nervous system regulates metabolic homeostasis in normal weight and obese rodents and humans. It includes a review of the homeostatic contributions of neurons located in the hypothalamus, the midbrain and limbic structures, the pons and the medullary area postrema, nucleus tractus solitarius, and vagus nucleus, and details how these brain regions respond to circulating levels of orexigenic hormones, such as ghrelin, and anorexigenic hormones...

  6. Metabolic Control and Academic Achievement over Time among Adolescents with Type 1 Diabetes

    Science.gov (United States)

    Winnick, Joel B.; Berg, Cynthia A.; Wiebe, Deborah J.; Schaefer, Barbara A.; Lei, Pui-Wa; Butner, Jonathan E.

    2017-01-01

    The relation between metabolic control (HbA1c) and achievement (grade point average [GPA]) was examined over a period of 2.5 years (every 6 months) employing a dynamical systems approach that allowed for the examination of whether HbA1c was associated with change in subsequent GPA and vice versa. Metabolic control tends to deteriorate (i.e., with…

  7. Silica dust control in small-scale building/structure demolition operations using good work practice guidance

    International Nuclear Information System (INIS)

    Muianga, C V; Rice, C H; Succop, P

    2009-01-01

    Work practices can influence exposure, especially in small-scale operations conducted by mobile work crews. This study evaluated the use of information on good work practice in control guidance sheets adapted from UK Silica Essentials guidance sheets by trained workers and supervisors employed in small-scale concrete and masonry demolition operations. A one-page employee silica task-based control guidance sheet for each of four demolition tasks and multiple-page silica control guidance for supervisors were developed. Interactive, hands-on worker training on these task-based good work practice controls was developed. Training was presented to 26 participants from two demolition crews. Feedback on the training and task-based good work practice control guidance sheets was elicited. Observations of work practices were made before and after training. Participants indicated gains in knowledge and checklists were used to document skill attainment. The quality of the training and usefulness of the material/skills was rated high by trainees. Increased use of water to suppress dust and wet cleaning methods on the job were documented following the training. Additional follow-up after training is required to determine long-term impact on sustained changes in work practices, and to evaluate the need for refresher training.

  8. Silica dust control in small-scale building/structure demolition operations using good work practice guidance

    Science.gov (United States)

    Muianga, C. V.; Rice, C. H.; Succop, P.

    2009-02-01

    Work practices can influence exposure, especially in small-scale operations conducted by mobile work crews. This study evaluated the use of information on good work practice in control guidance sheets adapted from UK Silica Essentials guidance sheets by trained workers and supervisors employed in small-scale concrete and masonry demolition operations. A one-page employee silica task-based control guidance sheet for each of four demolition tasks and multiple-page silica control guidance for supervisors were developed. Interactive, hands-on worker training on these task-based good work practice controls was developed. Training was presented to 26 participants from two demolition crews. Feedback on the training and task-based good work practice control guidance sheets was elicited. Observations of work practices were made before and after training. Participants indicated gains in knowledge and checklists were used to document skill attainment. The quality of the training and usefulness of the material/skills was rated high by trainees. Increased use of water to suppress dust and wet cleaning methods on the job were documented following the training. Additional follow-up after training is required to determine long-term impact on sustained changes in work practices, and to evaluate the need for refresher training.

  9. A Good Turn Deserves Another: Political Stability, Corruption and Corruption-Control

    OpenAIRE

    Simplice A Asongu

    2015-01-01

    We build on existing literature and contemporary challenges to African development to assess the role of political stability in fighting corruption and boosting corruption-control in 53 African countries for the period 1996-2010. We postulate that on the one hand, an atmosphere of political instability should increase the confidence of impunity owing to less corruption-control. On the other hand, in the absence such impunity from corruption, political instability further fuels corruption. Our...

  10. RNA quality control in yeast - what is good and what is bad?

    DEFF Research Database (Denmark)

    Andersen, Kasper Røjkjær; Brodersen, Ditlev Egeskov

    positions in the tRNA molecules [2]. We believe that in such cases, the tRNAs are recognized by a common structural alteration that causes part of the molecule to unfold and thereby mark the tRNA as defect. We therefore want to isolate and crystallize the RNA binding proteins Air1p or Air2p in complex...... with aberrant tRNA analogous to gain knowledge of how the cell determines which RNAs are good and bad and use this as a model system for how the cell in general recognizes aberrant RNAs. So far, Air1p and Air2p have been cloned from different yeast organisms and the first expression tests of the proteins have...

  11. Application of a controllable degron strategy for metabolic engineering

    DEFF Research Database (Denmark)

    Knuf, Christoph; Maury, Jerome; Jacobsen, Simo Abdessamad

    2014-01-01

    In numerous cases of metabolic engineering, metabolite pools have to be increased in order to obtain flux into heterologous pathways. A simple tool for this would be the deletion of genes that would practically lead to a block of the natural pathway, so that the carbon can flow into the heterolog...... of intermediates of the mevalonate pathway around 2,3-oxidosqualene, which is the precursor for triterpenoids. Many triterpenoids are pharmaceutically relevant compounds which nowadays need to be extracted from plant material through an intricate and resource consuming process....

  12. Detection of driver metabolites in the human liver metabolic network using structural controllability analysis

    Science.gov (United States)

    2014-01-01

    Background Abnormal states in human liver metabolism are major causes of human liver diseases ranging from hepatitis to hepatic tumor. The accumulation in relevant data makes it feasible to derive a large-scale human liver metabolic network (HLMN) and to discover important biological principles or drug-targets based on network analysis. Some studies have shown that interesting biological phenomenon and drug-targets could be discovered by applying structural controllability analysis (which is a newly prevailed concept in networks) to biological networks. The exploration on the connections between structural controllability theory and the HLMN could be used to uncover valuable information on the human liver metabolism from a fresh perspective. Results We applied structural controllability analysis to the HLMN and detected driver metabolites. The driver metabolites tend to have strong ability to influence the states of other metabolites and weak susceptibility to be influenced by the states of others. In addition, the metabolites were classified into three classes: critical, high-frequency and low-frequency driver metabolites. Among the identified 36 critical driver metabolites, 27 metabolites were found to be essential; the high-frequency driver metabolites tend to participate in different metabolic pathways, which are important in regulating the whole metabolic systems. Moreover, we explored some other possible connections between the structural controllability theory and the HLMN, and find that transport reactions and the environment play important roles in the human liver metabolism. Conclusion There are interesting connections between the structural controllability theory and the human liver metabolism: driver metabolites have essential biological functions; the crucial role of extracellular metabolites and transport reactions in controlling the HLMN highlights the importance of the environment in the health of human liver metabolism. PMID:24885538

  13. Control of mitochondrial metabolism and systemic energy homeostasis by microRNAs 378 and 378*.

    Science.gov (United States)

    Carrer, Michele; Liu, Ning; Grueter, Chad E; Williams, Andrew H; Frisard, Madlyn I; Hulver, Matthew W; Bassel-Duby, Rhonda; Olson, Eric N

    2012-09-18

    Obesity and metabolic syndrome are associated with mitochondrial dysfunction and deranged regulation of metabolic genes. Peroxisome proliferator-activated receptor γ coactivator 1β (PGC-1β) is a transcriptional coactivator that regulates metabolism and mitochondrial biogenesis through stimulation of nuclear hormone receptors and other transcription factors. We report that the PGC-1β gene encodes two microRNAs (miRNAs), miR-378 and miR-378*, which counterbalance the metabolic actions of PGC-1β. Mice genetically lacking miR-378 and miR-378* are resistant to high-fat diet-induced obesity and exhibit enhanced mitochondrial fatty acid metabolism and elevated oxidative capacity of insulin-target tissues. Among the many targets of these miRNAs, carnitine O-acetyltransferase, a mitochondrial enzyme involved in fatty acid metabolism, and MED13, a component of the Mediator complex that controls nuclear hormone receptor activity, are repressed by miR-378 and miR-378*, respectively, and are elevated in the livers of miR-378/378* KO mice. Consistent with these targets as contributors to the metabolic actions of miR-378 and miR-378*, previous studies have implicated carnitine O-acetyltransferase and MED13 in metabolic syndrome and obesity. Our findings identify miR-378 and miR-378* as integral components of a regulatory circuit that functions under conditions of metabolic stress to control systemic energy homeostasis and the overall oxidative capacity of insulin target tissues. Thus, these miRNAs provide potential targets for pharmacologic intervention in obesity and metabolic syndrome.

  14. Sodium bicarbonate on severe metabolic acidosis during prolonged cardiopulmonary resuscitation: a double-blind, randomized, placebo-controlled pilot study.

    Science.gov (United States)

    Ahn, Shin; Kim, Youn-Jung; Sohn, Chang Hwan; Seo, Dong Woo; Lim, Kyoung Soo; Donnino, Michael W; Kim, Won Young

    2018-04-01

    Sodium bicarbonate administration during cardiopulmonary resuscitation (CPR) is controversial. Current guidelines recommend sodium bicarbonate injection in patients with existing metabolic acidosis, but clinical trials, particularly, those involving patients with acidosis, are limited. We aimed to evaluate the efficacy of sodium bicarbonate administration in out-of-hospital cardiac arrest (OHCA) patients with severe metabolic acidosis during prolonged CPR. Prospective, double-blind, randomized placebo-controlled pilot trial was conducted between January 2015 and December 2015, at a single center emergency department (ED). After 10 minutes of CPR, patients who failed to achieve return of spontaneous circulation (ROSC) and with severe metabolic acidosis (pH<7.1 or bicarbonate <10 mEq/L) were enrolled. Sodium bicarbonate (n=25) or normal saline (n=25) were administered. The primary end point was sustained ROSC. The secondary end points were the change of acidosis and good neurologic survival. Sodium bicarbonate group had significant effect on pH (6.99 vs. 6.90, P=0.038) and bicarbonate levels (21.0 vs. 8.0 mEq/L, P=0.007). However, no significant differences showed between sodium bicarbonate and placebo groups in sustained ROSC (4.0% vs. 16.0%, P=0.349) or good neurologic survival at 1 month (0.0% vs. 4.0%, P=1.000). The use of sodium bicarbonate improved acid-base status, but did not improve the rate of ROSC and good neurologic survival. We could not draw a conclusion, but our pilot data could be used to design a larger trial to verify the efficacy of sodium bicarbonate. NCT02303548 (http://www.ClinicalTrials.gov).

  15. Iron metabolism in critically ill patients developing anemia of inflammation: a case control study.

    Science.gov (United States)

    Boshuizen, Margit; Binnekade, Jan M; Nota, Benjamin; van de Groep, Kirsten; Cremer, Olaf L; Tuinman, Pieter R; Horn, Janneke; Schultz, Marcus J; van Bruggen, Robin; Juffermans, Nicole P

    2018-05-02

    Anemia occurring as a result of inflammatory processes (anemia of inflammation, AI) has a high prevalence in critically ill patients. Knowledge on changes in iron metabolism during the course of AI is limited, hampering the development of strategies to counteract AI. This case control study aimed to investigate iron metabolism during the development of AI in critically ill patients. Iron metabolism in 30 patients who developed AI during ICU stay was compared with 30 septic patients with a high Hb and 30 non-septic patients with a high Hb. Patients were matched on age and sex. Longitudinally collected plasma samples were analyzed for levels of parameters of iron metabolism. A linear mixed model was used to assess the predictive values of the parameters. In patients with AI, levels of iron, transferrin and transferrin saturation showed an early decrease compared to controls with a high Hb, already prior to the development of anemia. Ferritin, hepcidin and IL-6 levels were increased in AI compared to controls. During AI development, erythroferrone decreased. Differences in iron metabolism between groups were not influenced by APACHE IV score. The results show that in critically ill patients with AI, iron metabolism is already altered prior to the development of anemia. Levels of iron regulators in AI differ from septic controls with a high Hb, irrespective of disease severity. AI is characterized by high levels of hepcidin, ferritin and IL-6 and low levels of iron, transferrin and erythroferrone.

  16. Measles control and elimination in Somalia: the good, the bad, and the ugly.

    Science.gov (United States)

    Kamadjeu, Raoul; Assegid, Kebede; Naouri, Boubker; Mirza, Imran Raza; Hirsi, Abdurazak; Mohammed, Abdurahman; Omer, Mohammed; Dualle, Abdi Hassan; Mulugeta, Abraham

    2011-07-01

    Despite enormous challenges, Somalia has been successfully implementing accelerated measles control activities since 2005. Through innovative strategies and with the support of local and international partners, the country has shown potentials of implementing measles mortality reduction activities in complex emergencies. Measles incidence has been reduced by >80% after the measles catch-up campaigns of 2005-2007, and national reported measles routine immunization coverage with first dose measles containing vaccine has reached 59% for the first time in 2009. However, the near collapse of the health care system and the ongoing insecurity continue to hamper the implementation of recommended measles control and elimination strategies in some parts of the country, making these achievements fragile. Somalia exemplifies the challenges in meeting measles elimination goals in the World Health Organization Eastern Mediterranean region. As the region is entering its 2010 measles elimination goals, it appears necessary to establish realistic and flexible interim goals for measles control in Somalia that will take into consideration the specificities of the country. Maintaining flexibility in conducting field operations, securing financial resources, multiplying opportunities for measles vaccination, and improving disease monitoring systems will remain vital to sustain and improve current achievements. © The Author 2011. Published by Oxford University Press on behalf of the Infectious Diseases Society of America. All rights reserved.

  17. Mammalian iron metabolism and its control by iron regulatory proteins☆

    Science.gov (United States)

    Anderson, Cole P.; Shen, Lacy; Eisenstein, Richard S.; Leibold, Elizabeth A.

    2013-01-01

    Cellular iron homeostasis is maintained by iron regulatory proteins 1 and 2 (IRP1 and IRP2). IRPs bind to iron-responsive elements (IREs) located in the untranslated regions of mRNAs encoding protein involved in iron uptake, storage, utilization and export. Over the past decade, significant progress has been made in understanding how IRPs are regulated by iron-dependent and iron-independent mechanisms and the pathological consequences of IRP2 deficiency in mice. The identification of novel IREs involved in diverse cellular pathways has revealed that the IRP–IRE network extends to processes other than iron homeostasis. A mechanistic understanding of IRP regulation will likely yield important insights into the basis of disorders of iron metabolism. This article is part of a Special Issue entitled: Cell Biology of Metals. PMID:22610083

  18. Heart over mind: metabolic control of white adipose tissue and liver.

    Science.gov (United States)

    Nakamura, Michinari; Sadoshima, Junichi

    2014-12-01

    Increasing evidence suggests that the heart controls the metabolism of peripheral organs. Olson and colleagues previously demonstrated that miR‐208a controls systemic energy homeostasis through the regulation of MED13 in cardiomyocytes (Grueter et al, 2012). In their follow‐up study in this issue of EMBO Molecular Medicine, white adipose tissue (WAT) and liver are identified as the physiological targets of cardiac MED13 signaling, most likely through cardiac‐derived circulating factors, which boost energy consumption by upregulating metabolic gene expression and increasing mitochondrial numbers (Baskin et al, 2014). In turn, increased energy expenditure in WAT and the liver confers leanness. These findings strengthen the evidence of metabolic crosstalk between the heart and peripheral tissues through cardiokines and also set the stage for the development of novel treatments for metabolic syndrome.

  19. How to determine control of growth rate in a chemostat. Using metabolic control analysis to resolve the paradox

    DEFF Research Database (Denmark)

    Snoep, Jacky L.; Jensen, Peter Ruhdal; Groeneveld, Philip

    1994-01-01

    how, paradoxically, one can determine control of growth rate, of growth yield and of other fluxes in a chemostat. We develop metabolic control analysis for the chemostat. this analysis does not depend on the particular way in which specific growth rate varies with the concentration of the growth...

  20. Association between metabolic control and oral health in adolescents with type 1 diabetes mellitus.

    Science.gov (United States)

    Saes Busato, Ivana Maria; Bittencourt, Mônica Sommer; Machado, Maria Angela Naval; Grégio, Ana Maria Trindade; Azevedo-Alanis, Luciana Reis

    2010-03-01

    The aim of this study was to evaluate the association between metabolic control and oral health of adolescents with type 1 diabetes mellitus (DM1). A case-control epidemiologic study was performed on adolescents allocated between 2 groups: DM1 group composed of 51 with DM1, and control group composed of 51 without diabetes. In the DM1 group, metabolic control data were observed (glycosylated hemoglobin (GHb) and capillary glucose), whereby GHb 8.0% poor metabolic control (DM1-B). Oral mucosal abnormalites, Community Periodontal Index (CPI), and decayed, missing, and filled (DMF) index were documented. Salivary flow was evaluated by means of stimulated saliva collection (SSFR). Glycosylated hemoglobin values of 8.0% (DM1-B) in 34 (76%) of the subjects. The average DMF indexes were 1.5 (control) and 3.3 (DM1-group) (P < or = .05). The average CPIs were 0.2 (control), 1.4 (DM1-A), and 2.0 (DM1-B) (P < or = .05). Average SSFRs were 0.997 (DM1-A), 0.903 (DM1-B), and 1.224 (control) mL/min. Oral health of adolescents with DM1 was impaired regardless of metabolic control. Copyright 2010 Mosby, Inc. All rights reserved.

  1. A Multifunctional Bread Rich in Beta Glucans and Low in Starch Improves Metabolic Control in Type 2 Diabetes: A Controlled Trial.

    Science.gov (United States)

    Tessari, Paolo; Lante, Anna

    2017-03-17

    Functional foods may be useful for people with diabetes. The soluble fibers beta glucans can modify starch digestion and improve postprandial glucose response. We analyzed the metabolic effects of a specifically designed 'functional' bread, low in starch, rich in fibers (7 g/100 g), with a beta glucan/starch ratio of (7.6:100, g/g), in people with type 2 diabetes mellitus. Methods : Clinical and metabolic data from two groups of age-, sex- and glycated hemoglobin-matched diabetic subjects, taking either the functional bread or regular white bread, over a roughly six-month observation period, were retrieved. Bread intake did not change during the trial. The functional bread reduced glycated hemoglobin by ~0.5% (absolute units) vs. pre-treatment values ( p = 0.028), and by ~0.6% vs. the control group ( p = 0.027). Post-prandial and mean plasma glucose was decreased in the treatment group too. Body weight, blood pressure and plasma lipids did not change. The acceptance of the functional bread was good in the majority of subjects, except for taste. A starch-restricted, fiber-rich functional bread, with an increased beta glucan/starch ratio, improved long term metabolic control, and may be indicated in the dietary treatment of type 2 diabetes.

  2. A Multifunctional Bread Rich in Beta Glucans and Low in Starch Improves Metabolic Control in Type 2 Diabetes: A Controlled Trial

    Science.gov (United States)

    Tessari, Paolo; Lante, Anna

    2017-01-01

    Design: Functional foods may be useful for people with diabetes. The soluble fibers beta glucans can modify starch digestion and improve postprandial glucose response. We analyzed the metabolic effects of a specifically designed ‘functional’ bread, low in starch, rich in fibers (7 g/100 g), with a beta glucan/starch ratio of (7.6:100, g/g), in people with type 2 diabetes mellitus. Methods: Clinical and metabolic data from two groups of age-, sex- and glycated hemoglobin-matched diabetic subjects, taking either the functional bread or regular white bread, over a roughly six-month observation period, were retrieved. Results: Bread intake did not change during the trial. The functional bread reduced glycated hemoglobin by ~0.5% (absolute units) vs. pre-treatment values (p = 0.028), and by ~0.6% vs. the control group (p = 0.027). Post-prandial and mean plasma glucose was decreased in the treatment group too. Body weight, blood pressure and plasma lipids did not change. The acceptance of the functional bread was good in the majority of subjects, except for taste. Conclusions: A starch-restricted, fiber-rich functional bread, with an increased beta glucan/starch ratio, improved long term metabolic control, and may be indicated in the dietary treatment of type 2 diabetes. PMID:28304350

  3. Good practice recommendations - medical-professional control of internal exposure to radionuclides in nuclear base installations

    International Nuclear Information System (INIS)

    Berard, Philippe; Blanchin, Nicolas; Fottorino, Robert; Gonin, Michele; Quesne, Benoit; Agrinier, Anne-Laure; Bourgaut, Laurent; Blanchardon, Eric; Challeton de Vathaire, Cecile; Franck, Didier; Piechowski, Jean; Fritsch, Paul; Poncy, Jean-Luc

    2011-07-01

    The first part of this voluminous report presents the context and method of definition of recommendations for a clinical practice and comprises a literature review of national, European and international recommendations, standards and work-group reports. The second part develops recommendations under four main themes: assessment of the committed effective dose (objectives, implementation, communication, traceability and archiving), control programs, dosimetric estimation based on results, and health risk and taking into care by the occupational physician. The authors adopted the same structure for each sub-theme or issue: target extract of regulatory and standard requirements and international recommendations, analysis of literature and of data from professional practices, opinion of the work-group, and graded recommendations with respect to the proof level

  4. A case-control pilot study of low-intensity IVF in good-prognosis patients.

    Science.gov (United States)

    Gleicher, Norbert; Weghofer, Andrea; Barad, David H

    2012-04-01

    Low-intensity IVF (LI-IVF) is rapidly gaining in popularity. Yet studies comparing LI-IVF to standard IVF are lacking. This is a case-control pilot study, reporting on 14 first LI-IVF and 14 standard IVF cycles in women with normal age-specific ovarian reserve under age 38, matched for age, laboratory environment, staff and time of cycle. LI-IVF cycles underwent mild ovarian stimulation, utilizing clomiphene citrate, augmented by low-dose gonadotrophin stimulation. Control patients underwent routine ovarian stimulation. LI-IVF and regular IVF patients were similar in age, body mass index, FSH and anti-Müllerian hormone. Standard IVF utilized more gonadotrophins (PIVF demonstrated better odds for pregnancy (OR 7.07; P=0.046) and higher cumulative pregnancy rates (63.3% versus 21.4%; OR 6.6; P=0.02). Adjustments for age, ethnicity and diagnosis maintained significance but oocyte adjustment did not. Cost assessments failed to reveal differences between LI-IVF and standard IVF. In this small study, LI-IVF reduced pregnancy chances without demonstrating cost advantages, raising questions about its utility. In the absence of established clinical and/or economic foundations, LI-IVF should be considered an experimental procedure. Low-intensity IVF (LI-IVF) is increasingly propagated as an alternative to standard IVF. LI-IVF has, however, never been properly assessed in comparison to standard IVF. Such a comparison is presented in the format of a small pilot study, matching LI-IVF cycles with regular IVF cycles and comparing outcomes as well as costs. The study suggests that LI-IVF, at least in this setting, is clinically inferior and economically at best similar to standard IVF. LI-IVF should, therefore, as of this point not be offered as routine IVF treatment but only as an experimental procedure. Copyright © 2012 Reproductive Healthcare Ltd. Published by Elsevier Ltd. All rights reserved.

  5. Taxing bads by taxing goods. Towards efficient pollution control with presumptive charges

    International Nuclear Information System (INIS)

    Eskeland, G.S.; Devarajan, S.

    1995-01-01

    A strong case is made for relying on a mix of indirect pollution control instruments - those which tax or regulate activities associated with emissions - rather than taxing the emissions themselves. They show that indirect instruments that reduce the scale of output (such as a tax on output or on polluting inputs) can be important complementary measures to emissions standards that reduce the level of emissions per unit of output. In this way, the effects of an optimal emission fee can be mimicked fairly well. The optimal mix of indirect instruments, however, requires knowledge of the 'cleaner' technologies (the ease with which emissions per unit of output can be reduced) as well as the sensitivity of demand to prices (the ease with which the scale of output can be reduced). This contrasts with the optimal emission fee, which relies only on information about emissions. The authors present empirically-based case studies to illustrate the consequences of employing a combination of presumptive charges and emissions standards. A recurring theme throughout their contribution is that the taxation of fuel use, due to the interaction between fuel use and emissions, can serve as a powerful indirect instrument to supplement pollution standards in controlling air pollution. In the case of automobiles, for example, they show that failing to employ gasoline taxes (which ensure that emissions are cut through not only cleaner cars but also fewer trips) in Mexico City would significantly harm welfare, even when regulatory standards (catalytic converters) are in place. In the case of point-source pollution, they calculate that significant potential exists for altering the fuel mix of industries in Indonesia and Chile by taxing 'dirtier' fuels. Furthermore, they show that, in the case of Indonesia, the general-equilibrium consequences of such a change in the tax structure are similar, though somewhat dampened, compared to what is indicated by partial-equilibrium models

  6. Metabolic control analysis of xylose catabolism in Aspergillus

    DEFF Research Database (Denmark)

    Prathumpai, Wai; Gabelgaard, J.B.; Wanchanthuek, P.

    2003-01-01

    , and flux control was shown to be dependent on the metabolite levels. Due to thermodynamic constraints, flux control may reside at the first step in the pathway, i.e., at the xylose reductase, even when the intracellular xylitol concentration is high. On the basis of the kinetic analysis, the general dogma...

  7. The Personality of a “Good Test Taker”: Self-Control and Mindfulness Predict Good Time-Management When Taking Exams

    Directory of Open Access Journals (Sweden)

    Jeffrey M. Osgood

    2017-09-01

    Full Text Available Much prior research has linked trait self-control and trait mindfulness with improved performance on overall academic metrics such as GPA. The present research expands on this literature by linking self-control, mindfulness, and closely related personality constructs to differences in the way students manage their time while taking exams. Students at two large public universities (total n = 362 completed scale measures of self-control, mindfulness, and their use of time when taking timed examinations. The results suggest that trait self-control (r = .174 and trait mindfulness (r = .311 are statistically significant predictors of effective time management while taking timed exams.

  8. Energy efficient lighting and controls at North Lanarkshire Council: Good practice case study

    Energy Technology Data Exchange (ETDEWEB)

    NONE

    2005-11-15

    The Sir Matt Busby Sports Complex is an important local facility for the people of Bellshill, North Lanarkshire. The sports and leisure complex, a North Lanarkshire Council property, offers a combination of indoor and outdoor sporting facilities including a floodlit synthetic football pitch and a comprehensive mix of swimming, sauna, gym and sports hall facilities. The electrical demand imposed by lighting for any business can be very significant, constituting up to 30% of the electrical power consumption. At the Sir Matt Busby Sports Complex a combination of new efficient light fittings and controls has improved lighting levels, reduced overall energy consumption by nearly 10% and provided substantial cost savings. The Carbon Trust has assisted the Council by identifying and prioritising energy saving opportunities and providing a prioritised implementation plan. This partnership arrangement and the Council's access to UK Pound 930,000 of 'spend to save' funding, provided by the Scottish Executive, has allowed the rapid implementation of energy efficiency measures. (GB)

  9. Giving in when feeling less good: Procrastination, action control, and social temptations.

    Science.gov (United States)

    Sirois, Fuschia M; Giguère, Benjamin

    2018-04-01

    Emotion-regulation perspectives on procrastination highlighting the primacy of short-term mood regulation focus mainly on negative affect. Positive affect, however, has received much less attention and has not been considered with respect to social temptations. To address this issue, we examined how trait procrastination was linked to positive and negative affect in the context of social temptations across two prospective studies. Action Control Theory, Personality Systems Interactions Theory, and a mood regulation theory of procrastination served as guiding conceptual frameworks. In Study 1, moderated mediation analyses revealed that low positive affect explained the link between trait procrastination and time spent procrastinating on academic tasks over a 48-hr period in a student sample (N = 142), and this effect was moderated by the presence of social temptations. Parallel results for goal enjoyment assessed at Time 2 were found in Study 2 with a community sample (N = 94) attempting to make intended health behaviour changes over a 6-month period. Our findings indicate that procrastinators are at risk for disengaging from intended tasks when social temptations are present and positive task-related affect is low. © 2018 The British Psychological Society.

  10. Dietary iron controls circadian hepatic glucose metabolism through heme synthesis.

    Science.gov (United States)

    Simcox, Judith A; Mitchell, Thomas Creighton; Gao, Yan; Just, Steven F; Cooksey, Robert; Cox, James; Ajioka, Richard; Jones, Deborah; Lee, Soh-Hyun; King, Daniel; Huang, Jingyu; McClain, Donald A

    2015-04-01

    The circadian rhythm of the liver maintains glucose homeostasis, and disruption of this rhythm is associated with type 2 diabetes. Feeding is one factor that sets the circadian clock in peripheral tissues, but relatively little is known about the role of specific dietary components in that regard. We assessed the effects of dietary iron on circadian gluconeogenesis. Dietary iron affects circadian glucose metabolism through heme-mediated regulation of the interaction of nuclear receptor subfamily 1 group d member 1 (Rev-Erbα) with its cosuppressor nuclear receptor corepressor 1 (NCOR). Loss of regulated heme synthesis was achieved by aminolevulinic acid (ALA) treatment of mice or cultured cells to bypass the rate-limiting enzyme in hepatic heme synthesis, ALA synthase 1 (ALAS1). ALA treatment abolishes differences in hepatic glucose production and in the expression of gluconeogenic enzymes seen with variation of dietary iron. The differences among diets are also lost with inhibition of heme synthesis with isonicotinylhydrazine. Dietary iron modulates levels of peroxisome proliferator-activated receptor γ coactivator 1α (PGC-1α), a transcriptional activator of ALAS1, to affect hepatic heme. Treatment of mice with the antioxidant N-acetylcysteine diminishes PGC-1α variation observed among the iron diets, suggesting that iron is acting through reactive oxygen species signaling. © 2015 by the American Diabetes Association. Readers may use this article as long as the work is properly cited, the use is educational and not for profit, and the work is not altered.

  11. Green leafy porridges: how good are they in controlling glycaemic response?

    Science.gov (United States)

    Anuruddhika Subhashinie Senadheera, Senadheera Pathirannehelage; Ekanayake, Sagarika

    2013-03-01

    Green leafy porridges made with leaf water extracts, rice and coconut milk are common Sri Lankan dietary remedies for diabetes. Though water and ethanolic extracts of most leaves elicit hypoglycaemic effects, data are not available on the efficacy when leaf extracts are incorporated into porridges. Thus, an effort was made to evaluate the proximate compositions and glycaemic index (GI) of some commonly consumed green leafy porridges. The GI of rice porridge and coconut milk porridge were measured to evaluate the effect of other ingredients other than the leaf extracts. Rice was the main contributor to carbohydrate (56-68% on dry weight) and water was the main component in porridges (89-93%). Fat and total dietary fibre contents ranged between 2.5-27% and 5-10%, respectively. The GI of all porridges was low (GI ≤ 55), except Cassia auriculata which had a high GI of 77 ± 12. The GIs of coconut milk, Aerva lanata, Hemidesmus indicus, Scoparia dulcis, Asparagus racemosus, Cephalandra indica, Cardiospermum halicacabum, Murraya koenigii and Aegle marmelos were 31 ± 5, 32 ± 5, 40 ± 8, 39 ± 8, 37 ± 4, 49 ± 8, 46 ± 8, 44 ± 8 and 50 ± 8, respectively. All porridges had a low or medium glycaemic loads ( ≤ 19). However, peak blood glucose reductions of ≥ 25% were observed in all leafy and coconut milk porridges, except in C. auriculata and Atlantia zeylanica, when compared with the glucose control. Therefore, green leafy porridges, except Cassia, can be recommended as breakfast meals for diabetics due to their low GI, peak blood glucose reduction and presence of other nutrients in green leaves.

  12. Current good manufacturing practice in manufacturing, processing, packing, or holding of drugs; revision of certain labeling controls. Final rule.

    Science.gov (United States)

    2012-03-20

    The Food and Drug Administration (FDA) is amending the packaging and labeling control provisions of the current good manufacturing practice (CGMP) regulations for human and veterinary drug products by limiting the application of special control procedures for the use of cut labeling to immediate container labels, individual unit cartons, or multiunit cartons containing immediate containers that are not packaged in individual unit cartons. FDA is also permitting the use of any automated technique, including differentiation by labeling size and shape, that physically prevents incorrect labeling from being processed by labeling and packaging equipment when cut labeling is used. This action is intended to protect consumers from labeling errors more likely to cause adverse health consequences, while eliminating the regulatory burden of applying the rule to labeling unlikely to reach or adversely affect consumers. This action is also intended to permit manufacturers to use a broader range of error prevention and labeling control techniques than permitted by current CGMPs.

  13. Guideline to good practices for control and calibration of measuring and test equipment (M ampersand TE) at DOE nuclear facilities

    International Nuclear Information System (INIS)

    1993-03-01

    The purpose of the Guideline to Good Practices for Control and Calibration of Measuring and Test Equipment (M ampersand TE) at DOE Nuclear Facilities is to provide contractor maintenance organizations with information that may be used for the development and implementation of a rigorously controlled maintenance program directed at controlling and calibrating M ampersand TE used for maintenance tasks at DOE nuclear facilities. This document is intended to be an example guideline for the implementation of DOE Order 4330.4A, Maintenance Management Program, Chapter II, Element 11. DOE contractors should not feel obligated to adopt all parts of this guide. Rather, they should use the information contained herein as a guide for developing an M ampersand TE program applicable to their facility

  14. A metabolic switch controls intestinal differentiation downstream of Adenomatous polyposis coli (APC).

    Science.gov (United States)

    Sandoval, Imelda T; Delacruz, Richard Glenn C; Miller, Braden N; Hill, Shauna; Olson, Kristofor A; Gabriel, Ana E; Boyd, Kevin; Satterfield, Christeena; Remmen, Holly Van; Rutter, Jared; Jones, David A

    2017-04-11

    Elucidating signaling pathways that regulate cellular metabolism is essential for a better understanding of normal development and tumorigenesis. Recent studies have shown that mitochondrial pyruvate carrier 1 (MPC1) , a crucial player in pyruvate metabolism, is downregulated in colon adenocarcinomas. Utilizing zebrafish to examine the genetic relationship between MPC1 and Adenomatous polyposis coli (APC), a key tumor suppressor in colorectal cancer, we found that apc controls the levels of mpc1 and that knock down of mpc1 recapitulates phenotypes of impaired apc function including failed intestinal differentiation. Exogenous human MPC1 RNA rescued failed intestinal differentiation in zebrafish models of apc deficiency. Our data demonstrate a novel role for apc in pyruvate metabolism and that pyruvate metabolism dictates intestinal cell fate and differentiation decisions downstream of apc .

  15. Emerging roles of the intestine in control of cholesterol metabolism

    NARCIS (Netherlands)

    Kruit, Janine-K.; Groen, Albert K.; van Berkel, Theo J.; Kuipers, Folkert

    2006-01-01

    The liver is considered the major "control center" for maintenance of whole body cholesterol homeostasis. This organ is the main site for de novo cholesterol synthesis, clears cholesterol-containing chylomicron remnants and low density lipoprotein particles from plasma and is the major contributor

  16. Roles for Orexin/Hypocretin in the Control of Energy Balance and Metabolism.

    Science.gov (United States)

    Goforth, Paulette B; Myers, Martin G

    The neuropeptide hypocretin is also commonly referred to as orexin, since its orexigenic action was recognized early. Orexin/hypocretin (OX) neurons project widely throughout the brain and the physiologic and behavioral functions of OX are much more complex than initially conceived based upon the stimulation of feeding. OX most notably controls functions relevant to attention, alertness, and motivation. OX also plays multiple crucial roles in the control of food intake, metabolism, and overall energy balance in mammals. OX signaling not only promotes food-seeking behavior upon short-term fasting to increase food intake and defend body weight, but, conversely, OX signaling also supports energy expenditure to protect against obesity. Furthermore, OX modulates the autonomic nervous system to control glucose metabolism, including during the response to hypoglycemia. Consistently, a variety of nutritional cues (including the hormones leptin and ghrelin) and metabolites (e.g., glucose, amino acids) control OX neurons. In this chapter, we review the control of OX neurons by nutritional/metabolic cues, along with our current understanding of the mechanisms by which OX and OX neurons contribute to the control of energy balance and metabolism.

  17. Metabolic Control and Illness Perceptions in Adolescents with Type 1 Diabetes

    Directory of Open Access Journals (Sweden)

    Line Wisting

    2016-01-01

    Full Text Available Background. Disturbed eating behavior and psychosocial variables have been found to influence metabolic control, but little is known about how these variables interact or how they influence metabolic control, separately and combined. Objective. To explore associations between metabolic control (measured by HbA1c and eating disorder psychopathology, coping strategies, illness perceptions, and insulin beliefs in adolescents with type 1 diabetes. Methods. A total of 105 patients (41.9% males with type 1 diabetes (12–20 years were interviewed with the Child Eating Disorder Examination. In addition, self-report psychosocial questionnaires were completed. Clinical data, including HbA1c, was obtained from the Norwegian Childhood Diabetes Registry. Results. Significant gender differences were demonstrated. Among females, HbA1c correlated significantly with eating restriction (.29, p < .05, the illness perception dimensions consequences, personal control, coherence, and concern (ranging from .33 to .48, and the coping strategy ventilating negative feelings (−.26, p < .05. Illness perception personal control contributed significantly to HbA1c in a regression model, explaining 23% of the variance among females (β .48, p < .001. None of the variables were significantly associated with HbA1c among males. Conclusions. Illness perceptions appear to be important contributors to metabolic control in females, but not males, with type 1 diabetes.

  18. Role of Parenting Style in Achieving Metabolic Control in Adolescents With Type 1 Diabetes

    OpenAIRE

    Shorer, Maayan; David, Ravit; Schoenberg-Taz, Michal; Levavi-Lavi, Ifat; Phillip, Moshe; Meyerovitch, Joseph

    2011-01-01

    OBJECTIVE To examine the role of parenting style in achieving metabolic control and treatment adherence in adolescents with type 1 diabetes. RESEARCH DESIGN AND METHODS Parents of 100 adolescents with type 1 diabetes completed assessments of their parenting style and sense of helplessness. Parents and patients rated patient adherence to the treatment regimen. Glycemic control was evaluated by HbA1c values. RESULTS An authoritative paternal parenting style predicted better glycemic control and...

  19. Control of Hepatic Glucose Metabolism by the Oral Hypoglycemic Sulfonylureas

    Science.gov (United States)

    1984-05-11

    diphosphate, 0.2 mM; 2,3 diphosphoglycerate , 0.1 mM; NADH, 0.2 mM; and 0.60 ml of deprotelnized sample. Pyruvate was measured by following the oxidation...J,; Rodgrlgues, L,M,; Whitton, P,A, and Hems, D,A, (1980) Control mechanisms in the acceleration of hepatic glycogen degradation during anoxia

  20. Modified metabolic syndrome and second cancers in women: A case control study.

    Science.gov (United States)

    Ortiz-Mendoza, Carlos-Manuel; Pérez-Chávez, Ernesto; Fuente-Vera, Tania-Angélica De-la

    2016-01-01

    According to some studies, the metabolic syndrome causes diverse primary cancers; however, there is no evidence about metabolic syndrome impact on second cancers development in women. To find out the implication of the modified metabolic syndrome in women with second cancers. This was a case-control study, at a general hospital in Mexico City, in women with second cancers (cases) and age-matched women with only one neoplasm (controls). The analysis comprised: Tumor (s), anthropometric features, and body mass index (BMI); moreover, presence of diabetes mellitus, hypertension, and fasting serum levels of total cholesterol, triglycerides and glucose. The sample was of nine cases and 27 controls. In cases, the metabolic syndrome (diabetes mellitus or glucose > 99 mg/dL + hypertension or blood pressure ≥ 135/85 mm Hg + triglycerides > 149 mg/dL or BMI ≥ 30 kg/m 2 ) was more frequent (odds ratio 20.8, 95% confidence interval: 1.9-227.1). Our results suggest that in women, the modified metabolic syndrome may be a risk factor for second cancers.

  1. Modified metabolic syndrome and second cancers in women: A case control study

    Directory of Open Access Journals (Sweden)

    Carlos-Manuel Ortiz-Mendoza

    2016-01-01

    Full Text Available Background: According to some studies, the metabolic syndrome causes diverse primary cancers; however, there is no evidence about metabolic syndrome impact on second cancers development in women. Aim: To find out the implication of the modified metabolic syndrome in women with second cancers. Materials and Methods: This was a case-control study, at a general hospital in Mexico City, in women with second cancers (cases and age-matched women with only one neoplasm (controls. The analysis comprised: Tumor (s, anthropometric features, and body mass index (BMI; moreover, presence of diabetes mellitus, hypertension, and fasting serum levels of total cholesterol, triglycerides and glucose. Results: The sample was of nine cases and 27 controls. In cases, the metabolic syndrome (diabetes mellitus or glucose > 99 mg/dL + hypertension or blood pressure ≥ 135/85 mm Hg + triglycerides > 149 mg/dL or BMI ≥ 30 kg/m 2 was more frequent (odds ratio 20.8, 95% confidence interval: 1.9-227.1. Conclusion: Our results suggest that in women, the modified metabolic syndrome may be a risk factor for second cancers.

  2. Control of Hepatic Glucose Metabolism by Islet and Brain

    Science.gov (United States)

    Rojas, Jennifer M.; Schwartz, Michael W.

    2014-01-01

    Dysregulation of hepatic glucose uptake (HGU) and inability of insulin to suppress hepatic glucose production (HGP), both contribute to hyperglycemia in patients with type 2 diabetes (T2D). Growing evidence suggests that insulin can inhibit HGP not only through a direct effect on the liver, but also via a mechanism involving the brain. Yet the notion that insulin action in the brain plays a physiological role in the control of HGP continues to be controversial. Although studies in dogs suggest that the direct hepatic effect of insulin is sufficient to explain day-to-day control of HGP, a surprising outcome has been revealed by recent studies in mice investigating whether the direct hepatic action of insulin is necessary for normal HGP: when hepatic insulin signaling pathway was genetically disrupted, HGP was maintained normally even in the absence of direct input from insulin. Here we present evidence that points to a potentially important role of the brain in the physiological control of both HGU and HGP in response to input from insulin as well as other hormones and nutrients. PMID:25200294

  3. Role of glycolytic intermediate in regulation: Improving lycopene production in Escherichia coli by engineering metabolic control

    Energy Technology Data Exchange (ETDEWEB)

    Farmer, W.R.; Liao, J.C.

    2001-06-01

    Metabolic engineering in the postgenomic era is expected to benefit from a full understanding of the biosynthetic capability of microorganisms as a result of the progress being made in bioinformatics and functional genomics. The immediate advantage of such information is to allow the rational design of novel pathways and the elimination of native reactions that are detrimental or unnecessary for the desired purpose. However, with the ability to manipulate metabolic pathways becoming more effective, metabolic engineering will need to face a new challenge: the reengineering of the regulatory hierarchy that controls gene expression in those pathways. In addition to constructing the genetic composition of a metabolic pathway, they propose that it will become just as important to consider the dynamics of pathways gene expression. It has been widely observed that high-level induction of a recombinant protein or pathway leads to growth retardation and reduced metabolic activity. These phenotypic characteristics result from the fact that the constant demands of production placed upon the cell interfere with its changing requirements for growth. They believe that this common situation in metabolic engineering can be alleviated by designing a dynamic controller that is able to sense the metabolic state of the cell and regulate the expression of the recombinant pathway accordingly. This approach, which is termed metabolic control engineering, involves redesigning the native regulatory circuits and applying them to the recombinant pathway. The general goal of such an effort will be to control the flux to the recombinant pathway adaptively according to the cell's metabolic state. The dynamically controlled recombinant pathway can potentially lead to enhanced production, minimized growth retardation, and reduced toxic by-product formation. The regulation of gene expression in response to the physiological state is also essential to the success of gene therapy. Here they

  4. The relative contribution of insulin secretory capacity, insulin action, and incretins to metabolic control after islet transplantation in dogs

    NARCIS (Netherlands)

    van der Burg, MPM; van Suylichem, PTR; Guicherit, OR; Frolich, M; Lemkes, HHPJ; Gooszen, HG

    Adequate metabolic control is central to the concept of islet transplantation, but has received limited attention. We studied metabolic control in 8 dogs at 6-9 months after intrasplenic autografting of similar to 25% of the normal mass islets - as compared to 30 controls. A similar posttransplant

  5. Evaluasi Penerapan Internal Control dan Pelaksanaan Good Corporate Governance pada PT PLN (Persero Distribusi Jakarta Raya dan Tangerang

    Directory of Open Access Journals (Sweden)

    Iswandi Iswandi

    2011-11-01

    Full Text Available PT. PLN (Persero Distribusi Jakarta Raya dan Tangerang have implemented Internal Control and Good Corporate Governance. The research would like to evaluate the implementation of Internal Control accordance with COSO’s criteria (Committee of Sponsoring Organizations of the Treadway Commission and KNKG’s criteria (Komite Nasional Kebijakan Governance. Based on research found that five components of COSO such as control environment, risk assessment, control activities, information and communication, monitoring have been implemented but unfortunately one of the component such as control activities not yet implemented properly accordance with COSO’s criteria. The company also have been imlemented GCG accordance with KNKG’s criteria but still need development through internalization GCG’s spirit among the employees because some employees still have different perception related to GCG. For example from employee stand point there’s no problem receive special gift or receive special payment from customer and have a conflict of interest when deal with public accountant.

  6. A dual control mechanism synchronizes riboflavin and sulphur metabolism in Bacillus subtilis

    Science.gov (United States)

    Pedrolli, Danielle Biscaro; Kühm, Christian; Sévin, Daniel C.; Vockenhuber, Michael P.; Sauer, Uwe; Suess, Beatrix; Mack, Matthias

    2015-01-01

    Flavin mononucleotide (FMN) riboswitches are genetic elements, which in many bacteria control genes responsible for biosynthesis and/or transport of riboflavin (rib genes). Cytoplasmic riboflavin is rapidly and almost completely converted to FMN by flavokinases. When cytoplasmic levels of FMN are sufficient (“high levels”), FMN binding to FMN riboswitches leads to a reduction of rib gene expression. We report here that the protein RibR counteracts the FMN-induced “turn-off” activities of both FMN riboswitches in Bacillus subtilis, allowing rib gene expression even in the presence of high levels of FMN. The reason for this secondary metabolic control by RibR is to couple sulfur metabolism with riboflavin metabolism. PMID:26494285

  7. [Metabolic control in the critically ill patient an update: hyperglycemia, glucose variability hypoglycemia and relative hypoglycemia].

    Science.gov (United States)

    Pérez-Calatayud, Ángel Augusto; Guillén-Vidaña, Ariadna; Fraire-Félix, Irving Santiago; Anica-Malagón, Eduardo Daniel; Briones Garduño, Jesús Carlos; Carrillo-Esper, Raúl

    Metabolic changes of glucose in critically ill patients increase morbidity and mortality. The appropriate level of blood glucose has not been established so far and should be adjusted for different populations. However concepts such as glucose variability and relative hypoglycemia of critically ill patients are concepts that are changing management methods and achieving closer monitoring. The purpose of this review is to present new data about the management and metabolic control of patients in critical areas. Currently glucose can no longer be regarded as an innocent element in critical patients; both hyperglycemia and hypoglycemia increase morbidity and mortality of patients. Protocols and better instruments for continuous measurement are necessary to achieve the metabolic control of our patients. Copyright © 2016 Academia Mexicana de Cirugía A.C. Publicado por Masson Doyma México S.A. All rights reserved.

  8. Synthetic control of a fitness tradeoff in yeast nitrogen metabolism

    Directory of Open Access Journals (Sweden)

    Lee Jack J

    2009-01-01

    Full Text Available Abstract Background Microbial communities are involved in many processes relevant to industrial and medical biotechnology, such as the formation of biofilms, lignocellulosic degradation, and hydrogen production. The manipulation of synthetic and natural microbial communities and their underlying ecological parameters, such as fitness, evolvability, and variation, is an increasingly important area of research for synthetic biology. Results Here, we explored how synthetic control of an endogenous circuit can be used to regulate a tradeoff between fitness in resource abundant and resource limited environments in a population of Saccharomyces cerevisiae. We found that noise in the expression of a key enzyme in ammonia assimilation, Gdh1p, mediated a tradeoff between growth in low nitrogen environments and stress resistance in high ammonia environments. We implemented synthetic control of an endogenous Gdh1p regulatory network to construct an engineered strain in which the fitness of the population was tunable in response to an exogenously-added small molecule across a range of ammonia environments. Conclusion The ability to tune fitness and biological tradeoffs will be important components of future efforts to engineer microbial communities.

  9. Urea and Ammonia Metabolism and the Control of Renal Nitrogen Excretion

    Science.gov (United States)

    Mitch, William E.; Sands, Jeff M.

    2015-01-01

    Renal nitrogen metabolism primarily involves urea and ammonia metabolism, and is essential to normal health. Urea is the largest circulating pool of nitrogen, excluding nitrogen in circulating proteins, and its production changes in parallel to the degradation of dietary and endogenous proteins. In addition to serving as a way to excrete nitrogen, urea transport, mediated through specific urea transport proteins, mediates a central role in the urine concentrating mechanism. Renal ammonia excretion, although often considered only in the context of acid-base homeostasis, accounts for approximately 10% of total renal nitrogen excretion under basal conditions, but can increase substantially in a variety of clinical conditions. Because renal ammonia metabolism requires intrarenal ammoniagenesis from glutamine, changes in factors regulating renal ammonia metabolism can have important effects on glutamine in addition to nitrogen balance. This review covers aspects of protein metabolism and the control of the two major molecules involved in renal nitrogen excretion: urea and ammonia. Both urea and ammonia transport can be altered by glucocorticoids and hypokalemia, two conditions that also affect protein metabolism. Clinical conditions associated with altered urine concentrating ability or water homeostasis can result in changes in urea excretion and urea transporters. Clinical conditions associated with altered ammonia excretion can have important effects on nitrogen balance. PMID:25078422

  10. Muscle insulin sensitivity and glucose metabolism are controlled by the intrinsic muscle clock

    DEFF Research Database (Denmark)

    Dyar, Kenneth A.; Ciciliot, Stefano; Wright, Lauren E.

    2014-01-01

    Circadian rhythms control metabolism and energy homeostasis, but the role of the skeletal muscle clock has never been explored. We generated conditional and inducible mouse lines with muscle-specific ablation of the core clock gene Bmal1. Skeletal muscles from these mice showed impaired insulin-s...

  11. The role of the autonomic nervous liver innervation in the control of energy metabolism

    NARCIS (Netherlands)

    Yi, Chun-Xia; la Fleur, Susanne E.; Fliers, Eric; Kalsbeek, Andries

    2010-01-01

    Despite a longstanding research interest ever since the early work by Claude Bernard, the functional significance of autonomic liver innervation, either sympathetic or parasympathetic, is still ill defined. This scarcity of information not only holds for the brain control of hepatic metabolism, but

  12. Radiopharmaceuticals good practices handbook: ARCAL XV radiopharmaceuticals control and production; Manual de buenas practicas radiofarmaceuticas: ARCAL XV produccion y control de radiofarmacos

    Energy Technology Data Exchange (ETDEWEB)

    Verdera Presto, Silvia [comp.; Universidad de la Republica, Facultad de ciencias, Centro de Investigaciones Nucleares, Montevideo (Uruguay)

    1999-12-31

    A safety practice of the therapeutics diagnostic proceeding in nuclear medicine require a permanent provide high quality radiopharmaceuticals manufacture. This work treat to give a guide for all radio pharmacies laboratories that produce,control, fraction and or dispense radiopharmaceuticals products, with attention hospitable radiopharmacy laboratory. Three chapters with recommendations in manufacture good practice in Hospital radiopharmacy, industrial centralized, bibliography and three annexe`s about clean area classification,standards work in laminar flux bell, and guarantee and cleaning areas

  13. Good leadership for good quality

    OpenAIRE

    Franzon, Vilma Maria

    2016-01-01

    Good leadership is important if you like to have high quality in the results. My experience in the production of the television industry is that conditions for good leadership is insufficient. Therefore, I have tried to get answers for those two questions in my exam report: What are the characteristics of good leadership? What are the prerequisites for good leadership out of production? The method I used is a literature study and observation. I have read a number of books and research studies...

  14. SIRT4 Is a Lysine Deacylase that Controls Leucine Metabolism and Insulin Secretion

    DEFF Research Database (Denmark)

    Anderson, Kristin A; Huynh, Frank K; Fisher-Wellman, Kelsey

    2017-01-01

    in leucine oxidation, and we show a primary role for SIRT4 in controlling this pathway in mice. Furthermore, we find that dysregulated leucine metabolism in SIRT4KO mice leads to elevated basal and stimulated insulin secretion, which progressively develops into glucose intolerance and insulin resistance....... These findings identify a robust enzymatic activity for SIRT4, uncover a mechanism controlling branched-chain amino acid flux, and position SIRT4 as a crucial player maintaining insulin secretion and glucose homeostasis during aging....

  15. Vulnerability to stress, anxiety and depressive symptoms and metabolic control in Type 2 diabetes

    Directory of Open Access Journals (Sweden)

    Gois Carlos

    2012-06-01

    Full Text Available Abstract Background Vulnerability to stress has been associated to distress, emotional distress symptoms and metabolic control in type 2 diabetes mellitus (T2DM patients as well. Furthermore some conflicting results were noticed. We aimed to evaluate the effect over metabolic control in what concerns vulnerability to stress beyond depressive and anxiety symptoms. Findings This cross-sectional study assessed 273 T2DM patients with depressive and anxiety symptoms using the Hospital Anxiety Depression Scale (HADS and the 23 Questions to assess Vulnerability to Stress (23QVS, along with demographic and clinical diabetes-related variables. Hierarchical logistic regression models were used to investigate predictors of poor glycemic control. The results showed an association of depressive symptoms (odds ratio = 1.12, 95%CI = 1.01-1.24, P = 0.030 with increased risk of poor glycemic control. Anxiety symptoms and vulnerability to stress on their own were not predictive of metabolic control, respectively (odds ratio = 0.92, 95%CI = 0.84-1.00, P = 0.187 and odds ratio = 0.98, 95%CI = 0.95-1.01, P = 0.282. Conclusions Our data suggested that vulnerability to stress was not predictive of poor glycemic control in T2DM, but depressive symptoms were.

  16. Alcohol decreases baseline brain glucose metabolism more in heavy drinkers than controls but has no effect on stimulation-induced metabolic increases.

    Science.gov (United States)

    Volkow, Nora D; Wang, Gene-Jack; Shokri Kojori, Ehsan; Fowler, Joanna S; Benveniste, Helene; Tomasi, Dardo

    2015-02-18

    During alcohol intoxication, the human brain increases metabolism of acetate and decreases metabolism of glucose as energy substrate. Here we hypothesized that chronic heavy drinking facilitates this energy substrate shift both for baseline and stimulation conditions. To test this hypothesis, we compared the effects of alcohol intoxication (0.75 g/kg alcohol vs placebo) on brain glucose metabolism during video stimulation (VS) versus when given with no stimulation (NS), in 25 heavy drinkers (HDs) and 23 healthy controls, each of whom underwent four PET-(18)FDG scans. We showed that resting whole-brain glucose metabolism (placebo-NS) was lower in HD than controls (13%, p = 0.04); that alcohol (compared with placebo) decreased metabolism more in HD (20 ± 13%) than controls (9 ± 11%, p = 0.005) and in proportion to daily alcohol consumption (r = 0.36, p = 0.01) but found that alcohol did not reduce the metabolic increases in visual cortex from VS in either group. Instead, VS reduced alcohol-induced decreases in whole-brain glucose metabolism (10 ± 12%) compared with NS in both groups (15 ± 13%, p = 0.04), consistent with stimulation-related glucose metabolism enhancement. These findings corroborate our hypothesis that heavy alcohol consumption facilitates use of alternative energy substrates (i.e., acetate) for resting activity during intoxication, which might persist through early sobriety, but indicate that glucose is still favored as energy substrate during brain stimulation. Our findings are consistent with reduced reliance on glucose as the main energy substrate for resting brain metabolism during intoxication (presumably shifting to acetate or other ketones) and a priming of this shift in HDs, which might make them vulnerable to energy deficits during withdrawal. Copyright © 2015 the authors 0270-6474/15/353248-08$15.00/0.

  17. Alcohol decreases baseline brain glucose metabolism more in heavy drinkers than controls but has no effect on stimulation-induced metabolic increases

    International Nuclear Information System (INIS)

    Volkow, Nora D.; Fowler, Joanna S.; Wang, Gene-Jack; Kojori, Eshan Shokri; Benveniste, Helene; Tomasi, Dardo

    2015-01-01

    During alcohol intoxication the human brain increases metabolism of acetate and decreases metabolism of glucose as energy substrate. Here we hypothesized that chronic heavy drinking facilitates this energy substrate shift both for baseline and stimulation conditions. To test this hypothesis we compared the effects of alcohol intoxication (0.75g/kg alcohol versus placebo) on brain glucose metabolism during video-stimulation (VS) versus when given with no-stimulation (NS), in 25 heavy drinkers (HD) and 23 healthy controls each of whom underwent four PET- 18 FDG scans. We showed that resting whole-brain glucose metabolism (placebo-NS) was lower in HD than controls (13%, p=0.04); that alcohol (compared to placebo) decreased metabolism more in HD (20±13%) than controls (9±11%, p=0.005) and in proportion to daily alcohol consumption (r=0.36, p=0.01) but found that alcohol did not reduce the metabolic increases in visual cortex from VS in either group. Instead, VS reduced alcohol-induced decreases in whole-brain glucose metabolism (10±12%) compared to NS in both groups (15±13%, p=0.04), consistent with stimulation-related glucose metabolism enhancement. These findings corroborate our hypothesis that heavy alcohol consumption facilitates use of alternative energy substrates (i.e. acetate) for resting activity during intoxication, which might persist through early sobriety, but indicate that glucose is still favored as energy substrate during brain stimulation. Our findings are consistent with reduced reliance on glucose as the main energy substrate for resting brain metabolism during intoxication (presumably shifting to acetate or other ketones) and a priming of this shift in heavy drinkers, which might make them vulnerable to energy deficits during withdrawal

  18. Combined Effects of Ezetimibe and Phytosterols on Cholesterol Metabolism: A Randomized, Controlled Feeding Study in Humans

    Science.gov (United States)

    Lin, Xiaobo; Racette, Susan B.; Lefevre, Michael; Ma, Lina; Spearie, Catherine Anderson; Steger-May, Karen; Ostlund, Richard E.

    2011-01-01

    Background Both ezetimibe and phytosterols inhibit cholesterol absorption. We tested the hypothesis that ezetimibe combined with phytosterols is more effective than ezetimibe alone in altering cholesterol metabolism. Methods and Results Twenty-one mildly hypercholesterolemic subjects completed a randomized, double-blind, placebo-controlled, triple crossover study. Each subject received a phytosterol-controlled diet plus (1) ezetimibe placebo + phytosterol placebo, (2) 10 mg ezetimibe/day + phytosterol placebo, and (3) 10 mg ezetimibe/day + 2.5 g phytosterols/day, for 3 weeks each. All meals were prepared in a metabolic kitchen. Primary outcomes were intestinal cholesterol absorption, fecal cholesterol excretion, and LDL cholesterol levels. The combined treatment resulted in significantly lower intestinal cholesterol absorption (598 mg/day, 95% CI 368 to 828) relative to control (2161 mg/day, 1112 to 3209) and ezetimibe alone (1054 mg/day, 546 to 1561, both P phytosterols averaged 129 (95% CI: 116 to 142), 108 (97 to 119), and 101 (90 to 112) mg/dL (P phytosterols to ezetimibe significantly enhanced the effects of ezetimibe on whole-body cholesterol metabolism and plasma LDL cholesterol. The large cumulative action of combined dietary and pharmacologic treatment on cholesterol metabolism emphasizes the potential importance of dietary phytosterols as adjunctive therapy for the treatment of hypercholesterolemia. PMID:21768544

  19. Thyroid peroxidase antibodies in pregnant women with type 1 diabetes: impact on thyroid function, metabolic control and pregnancy outcome

    DEFF Research Database (Denmark)

    Vestgaard, Marianne; Nielsen, Lene Ringholm; Rasmussen, Åse Krogh

    2008-01-01

    In pregnant women with type 1 diabetes, we evaluated whether the presence of thyroid peroxidase autoantibodies (anti-TPO) was associated with changes in thyroid function, metabolic control and pregnancy outcome.......In pregnant women with type 1 diabetes, we evaluated whether the presence of thyroid peroxidase autoantibodies (anti-TPO) was associated with changes in thyroid function, metabolic control and pregnancy outcome....

  20. Impact of hypothalamic reactive oxygen species in the control of energy metabolism and food intake

    Directory of Open Access Journals (Sweden)

    Anne eDrougard

    2015-02-01

    Full Text Available Hypothalamus is a key area involved in the control of metabolism and food intake via the integrations of numerous signals (hormones, neurotransmitters, metabolites from various origins. These factors modify hypothalamic neurons activity and generate adequate molecular and behavioral responses to control energy balance. In this complex integrative system, a new concept has been developed in recent years, that includes reactive oxygen species (ROS as a critical player in energy balance. ROS are known to act in many signaling pathways in different peripheral organs, but also in hypothalamus where they regulate food intake and metabolism by acting on different types of neurons, including proopiomelanocortin (POMC and agouti-related protein (AgRP/neuropeptide Y (NPY neurons. Hypothalamic ROS release is under the influence of different factors such as pancreatic and gut hormones, adipokines (leptin, apelin,..., neurotransmitters and nutrients (glucose, lipids,.... The sources of ROS production are multiple including NADPH oxidase, but also the mitochondria which is considered as the main ROS producer in the brain. ROS are considered as signaling molecules, but conversely impairment of this neuronal signaling ROS pathway contributes to alterations of autonomic nervous system and neuroendocrine function, leading to metabolic diseases such as obesity and type 2 diabetes.In this review we focus our attention on factors that are able to modulate hypothalamic ROS release in order to control food intake and energy metabolism, and whose deregulations could participate to the development of pathological conditions. This novel insight reveals an original mechanism in the hypothalamus that controls energy balance and identify hypothalamic ROS signaling as a potential therapeutic strategy to treat metabolic disorders.

  1. Lack of hippocampal volume differences in primary insomnia and good sleeper controls: an MRI volumetric study at 3 Tesla.

    Science.gov (United States)

    Winkelman, John W; Benson, Kathleen L; Buxton, Orfeu M; Lyoo, In Kyoon; Yoon, Sujung; O'Connor, Shawn; Renshaw, Perry F

    2010-06-01

    A recent pilot study reported that hippocampal volume (HV) was reduced in patients with primary insomnia (PI) relative to normal sleepers. Loss of HV in PI might be due to chronic hyperarousal and/or chronic sleep debt. The aim of this study was to replicate the earlier pilot report while employing a larger sample, more rigorous screening criteria, and objective sleep data. This cross-sectional design included community recruits meeting DSM-IV criteria for PI (n=20, 10 males, mean age 39.3+/-8.7) or good sleeper controls (n=15, 9 males, mean age 38.8+/-5.3). All subjects were unmedicated and rigorously screened to exclude comorbid psychiatric and medical illness. PI subjects underwent overnight polysomnography to screen for sleep-related breathing and movement disorders. HV and total brain volumes were derived by MRI employing a Siemens/Trio scanner operating at 3 Tesla. Data also included 2 weeks of sleep diaries and wrist actigraphy. Mean HV was 4322.0+/-299.7 mm(3) for the good sleeper controls and 4601.55+/-537.4 mm(3) for the PI group. The dependent variable, HV, was analyzed by ANCOVA. Main effects were diagnosis and gender; whole brain volume served as the covariate. Although the overall model was significant (F=6.3, p=0.001), the main effects of diagnosis (F=2.14) and gender (F=0.04) were not significant. The covariate of whole brain volume was significant (F=5.74, p=0.023) as was the interaction of diagnosis with gender (F=10.22, p=0.003), with male insomniacs having larger HVs than male controls. This study did not replicate a previously published report of HV loss in primary insomnia. Differences between our finding and the previous report might be due to sample composition and method of MRI assessment. Furthermore, we demonstrated no objective differences between the controls and PIs in actigraphic measures of sleep maintenance. Within the PIs, however, actigraphic measures of poor sleep maintenance were associated with smaller HV. Copyright 2010

  2. Metabolic Control of Dendritic Cell Activation and Function: Recent Advances and Clinical Implications

    Directory of Open Access Journals (Sweden)

    Bart eEverts

    2014-05-01

    Full Text Available Dendritic cells (DCs are key regulators of both immunity and tolerance by controlling activation and polarization of effector T helper cell and regulatory T cell responses. Therefore, there is a major focus on developing approaches to manipulate DC function for immunotherapy. It is well known that changes in cellular activation are coupled to profound changes in cellular metabolism. Over the past decade there is a growing appreciation that these metabolic changes also underlie the capacity of immune cells to perform particular functions. This has led to the concept that the manipulation of cellular metabolism can be used to shape innate and adaptive immune responses. While most of our understanding in this area has been gained from studies with T cells and macrophages, evidence is emerging that the activation and function of DCs are also dictated by the type of metabolism these cells commit to. We here discuss these new insights and explore whether targeting of metabolic pathways in DCs could hold promise as a novel approach to manipulate the functional properties of DCs for clinical purposes.

  3. Metabolism and the Control of Cell Fate Decisions and Stem Cell Renewal

    Science.gov (United States)

    Ito, Kyoko; Ito, Keisuke

    2016-01-01

    Although the stem cells of various tissues remain in the quiescent state to maintain their undifferentiated state, they also undergo cell divisions as required, and if necessary, even a single stem cell is able to provide for lifelong tissue homeostasis. Stem cell populations are precisely controlled by the balance between their symmetric and asymmetric divisions, with their division patterns determined by whether the daughter cells involved retain their self-renewal capacities. Recent studies have reported that metabolic pathways and the distribution of mitochondria are regulators of the division balance of stem cells and that metabolic defects can shift division balance toward symmetric commitment, which leads to stem cell exhaustion. It has also been observed that in asymmetric division, old mitochondria, which are central metabolic organelles, are segregated to the daughter cell fated to cell differentiation, whereas in symmetric division, young and old mitochondria are equally distributed between both daughter cells. Thus, metabolism and mitochondrial biology play important roles in stem cell fate decisions. As these decisions directly affect tissue homeostasis, understanding their regulatory mechanisms in the context of cellular metabolism is critical. PMID:27482603

  4. Monitoring and robust adaptive control of fed-batch cultures of microorganisms exhibiting overflow metabolism [abstract

    Directory of Open Access Journals (Sweden)

    Vande Wouwer, A.

    2010-01-01

    Full Text Available Overflow metabolism characterizes cells strains that are likely to produce inhibiting by-products resulting from an excess of substrate feeding and a saturated respiratory capacity. The critical substrate level separating the two different metabolic pathways is generally not well defined. Monitoring of this kind of cultures, going from model identification to state estimation, is first discussed. Then, a review of control techniques which all aim at maximizing the cell productivity of fed-batch fermentations is presented. Two main adaptive control strategies, one using an estimation of the critical substrate level as set-point and another regulating the by-product concentration, are proposed. Finally, experimental investigations of an adaptive RST control scheme using the observer polynomial for the regulation of the ethanol concentration in Saccharomyces cerevisiae fed-batch cultures ranging from laboratory to industrial scales, are also presented.

  5. Identification of microRNAs controlling hepatic mRNA levels for metabolic genes during the metabolic transition from embryonic to posthatch development in the chicken.

    Science.gov (United States)

    Hicks, Julie A; Porter, Tom E; Liu, Hsiao-Ching

    2017-09-05

    The transition from embryonic to posthatch development in the chicken represents a massive metabolic switch from primarily lipolytic to primarily lipogenic metabolism. This metabolic switch is essential for the chick to successfully transition from the metabolism of stored egg yolk to the utilization of carbohydrate-based feed. However, regulation of this metabolic switch is not well understood. We hypothesized that microRNAs (miRNAs) play an important role in the metabolic switch that is essential to efficient growth of chickens. We used high-throughput RNA sequencing to characterize expression profiles of mRNA and miRNA in liver during late embryonic and early posthatch development of the chicken. This extensive data set was used to define the contributions of microRNAs to the metabolic switch during development that is critical to growth and nutrient utilization in chickens. We found that expression of over 800 mRNAs and 30 miRNAs was altered in the embryonic liver between embryonic day 18 and posthatch day 3, and many of these differentially expressed mRNAs and miRNAs are associated with metabolic processes. We confirmed the regulation of some of these mRNAs by miRNAs expressed in a reciprocal pattern using luciferase reporter assays. Finally, through the use of yeast one-hybrid screens, we identified several proteins that likely regulate expression of one of these important miRNAs. Integration of the upstream regulatory mechanisms governing miRNA expression along with monitoring the downstream effects of this expression will ultimately allow for the construction of complete miRNA regulatory networks associated with the hepatic metabolic switch in chickens. Our findings support a key role for miRNAs in controlling the metabolic switch that occurs between embryonic and posthatch development in the chicken.

  6. 78 FR 11611 - Current Good Manufacturing Practice and Hazard Analysis and Risk-Based Preventive Controls for...

    Science.gov (United States)

    2013-02-19

    ... related to the proposed rule on ``Current Good Manufacturing Practice and Hazard Analysis and Risk-Based... . All comments should be identified with the title ``Current Good Manufacturing Practice and Hazard... rulemaking to modernize the regulation for ``Current Good Manufacturing Practice In Manufacturing, Packing...

  7. 78 FR 69604 - Current Good Manufacturing Practice and Hazard Analysis and Risk-Based Preventive Controls for...

    Science.gov (United States)

    2013-11-20

    ... Federal Register of January 16, 2013 (78 FR 3646), entitled ``Current Good Manufacturing Practice and... a proposed rule entitled ``Current Good Manufacturing Practice and Hazard Analysis and Risk-Based..., 114, 117, 120, 123, 129, 179, and 211 [Docket No. FDA-2011-N-0920] RIN 0910-AG36 Current Good...

  8. 78 FR 48636 - Current Good Manufacturing Practice and Hazard Analysis and Risk-Based Preventive Controls for...

    Science.gov (United States)

    2013-08-09

    ... collection related to the proposed rule, ``Current Good Manufacturing Practice and Hazard Analysis and Risk... period. These two proposals are related to the proposed rule ``Current Good Manufacturing Practice and... final extension of the comment period for the ``Current Good Manufacturing Practice and Hazard Analysis...

  9. The Role of Monoaminergic Neurotransmission for Metabolic Control in the Fruit Fly Drosophila Melanogaster

    Directory of Open Access Journals (Sweden)

    Yong Li

    2017-08-01

    Full Text Available Hormones control various metabolic traits comprising fat deposition or starvation resistance. Here we show that two invertebrate neurohormones, octopamine (OA and tyramine (TA as well as their associated receptors, had a major impact on these metabolic traits. Animals devoid of the monoamine OA develop a severe obesity phenotype. Using flies defective in the expression of receptors for OA and TA, we aimed to decipher the contributions of single receptors for these metabolic phenotypes. Whereas those animals impaired in octß1r, octß2r and tar1 share the obesity phenotype of OA-deficient (tβh-deficient animals, the octß1r, octß2r deficient flies showed reduced insulin release, which is opposed to the situation found in tβh-deficient animals. On the other hand, OAMB deficient flies were leaner than controls, implying that the regulation of this phenotype is more complex than anticipated. Other phenotypes seen in tβh-deficient animals, such as the reduced ability to perform complex movements tasks can mainly be attributed to the octß2r. Tissue-specific RNAi experiments revealed a very complex interorgan communication leading to the different metabolic phenotypes observed in OA or OA and TA-deficient flies.

  10. Risk of metabolic syndrome among children living in metropolitan Kuala Lumpur: a case control study.

    Science.gov (United States)

    Wee, Bee S; Poh, Bee K; Bulgiba, Awang; Ismail, Mohd N; Ruzita, Abdul T; Hills, Andrew P

    2011-05-18

    With the increasing prevalence of childhood obesity, the metabolic syndrome has been studied among children in many countries but not in Malaysia. Hence, this study aimed to compare metabolic risk factors between overweight/obese and normal weight children and to determine the influence of gender and ethnicity on the metabolic syndrome among school children aged 9-12 years in Kuala Lumpur and its metropolitan suburbs. A case control study was conducted among 402 children, comprising 193 normal-weight and 209 overweight/obese. Weight, height, waist circumference (WC) and body composition were measured, and WHO (2007) growth reference was used to categorise children into the two weight groups. Blood pressure (BP) was taken, and blood was drawn after an overnight fast to determine fasting blood glucose (FBG) and full lipid profile, including triglycerides (TG), high-density lipoprotein cholesterol (HDL-C), low-density lipoprotein cholesterol (LDL-C) and total cholesterol (TC). International Diabetes Federation (2007) criteria for children were used to identify metabolic syndrome. Participants comprised 60.9% (n = 245) Malay, 30.9% (n = 124) Chinese and 8.2% (n = 33) Indian. Overweight/obese children showed significantly poorer biochemical profile, higher body fat percentage and anthropometric characteristics compared to the normal-weight group. Among the metabolic risk factors, WC ≥90th percentile was found to have the highest odds (OR = 189.0; 95%CI 70.8, 504.8), followed by HDL-C≤1.03 mmol/L (OR = 5.0; 95%CI 2.4, 11.1) and high BP (OR = 4.2; 95%CI 1.3, 18.7). Metabolic syndrome was found in 5.3% of the overweight/obese children but none of the normal-weight children (p < 0.01). Overweight/obese children had higher odds (OR = 16.3; 95%CI 2.2, 461.1) of developing the metabolic syndrome compared to normal-weight children. Binary logistic regression showed no significant association between age, gender and family history of communicable diseases with the metabolic

  11. Lansoprazole Is Associated with Worsening Asthma Control in Children with the CYP2C19 Poor Metabolizer Phenotype.

    Science.gov (United States)

    Lang, Jason E; Holbrook, Janet T; Mougey, Edward B; Wei, Christine Y; Wise, Robert A; Teague, W Gerald; Lima, John J

    2015-06-01

    Gastric acid blockade in children with asymptomatic acid reflux has not improved asthma control in published studies. There is substantial population variability regarding metabolism of and response to proton pump inhibitors based on metabolizer phenotype. How metabolizer phenotype affects asthma responses to acid blockage is not known. To determine how metabolizer phenotype based on genetic analysis of CYP2C19 affects asthma control among children treated with a proton pump inhibitor. Asthma control as measured by the Asthma Control Questionnaire (ACQ) and other questionnaires from a 6-month clinical trial of lansoprazole in children with asthma was analyzed for associations with surrogates of lansoprazole exposure (based on treatment assignment and metabolizer phenotype). Groups included placebo-treated children; lansoprazole-treated extensive metabolizers (EMs); and lansoprazole-treated poor metabolizers (PMs). Metabolizer phenotypes were based on CYP2C19 haplotypes. Carriers of the CYP2C19*2, *3, *8, *9, or *10 allele were PMs; carriers of two wild-type alleles were extensive metabolizers (EMs). Asthma control through most of the treatment period was unaffected by lansoprazole exposure or metabolizer phenotype. At 6 months, PMs displayed significantly worsened asthma control compared with EMs (+0.16 vs. -0.13; P = 0.02) and placebo-treated children (+0.16 vs. -0.23; P lansoprazole-treated PMs. Children with the PM phenotype developed worse asthma control after 6 months of lansoprazole treatment for poorly controlled asthma. Increased exposure to proton pump inhibitor may worsen asthma control by altering responses to respiratory infections. Clinical trial registered with www.clinicaltrials.gov (NCT00604851).

  12. Defining a novel leptin–melanocortin–kisspeptin pathway involved in the metabolic control of puberty

    Directory of Open Access Journals (Sweden)

    Maria Manfredi-Lozano

    2016-10-01

    Full Text Available Objective: Puberty is a key developmental phenomenon highly sensitive to metabolic modulation. Worrying trends of changes in the timing of puberty have been reported in humans. These might be linked to the escalating prevalence of childhood obesity and could have deleterious impacts on later (cardio-metabolic health, but their underlying mechanisms remain unsolved. The neuropeptide α-MSH, made by POMC neurons, plays a key role in energy homeostasis by mediating the actions of leptin and likely participates in the control of reproduction. However, its role in the metabolic regulation of puberty and interplay with kisspeptin, an essential puberty-regulating neuropeptide encoded by Kiss1, remain largely unknown. We aim here to unveil the potential contribution of central α-MSH signaling in the metabolic control of puberty by addressing its role in mediating the pubertal effects of leptin and its potential interaction with kisspeptin. Methods: Using wild type and genetically modified rodent models, we implemented pharmacological studies, expression analyses, electrophysiological recordings, and virogenetic approaches involving DREADD technology to selectively inhibit Kiss1 neurons, in order to interrogate the physiological role of a putative leptin→α-MSH→kisspeptin pathway in the metabolic control of puberty. Results: Stimulation of central α-MSH signaling robustly activated the reproductive axis in pubertal rats, whereas chronic inhibition of melanocortin receptors MC3/4R, delayed puberty, and prevented the permissive effect of leptin on puberty onset. Central blockade of MC3/4R or genetic elimination of kisspeptin receptors from POMC neurons did not affect kisspeptin effects. Conversely, congenital ablation of kisspeptin receptors or inducible, DREADD-mediated inhibition of arcuate nucleus (ARC Kiss1 neurons resulted in markedly attenuated gonadotropic responses to MC3/4R activation. Furthermore, close appositions were observed between

  13. Photoperiodism and enzyme activity: towards a model for the control of circadian metabolic rhythms in the crassulacean Acid metabolism.

    Science.gov (United States)

    Queiroz, O; Morel, C

    1974-04-01

    Metabolic readjustments after a change from long days to short days appear, in Kalanchoe blossfeldiana, to be achieved through the operation of two main mechanisms: variation in enzyme capacity, and circadian rhythmicity. After a lag time, capacity in phosphoenolpyruvate carboxylase and capacity in aspartate aminotransferase increase exponentially and appear to be allometrically linked during 50 to 60 short days; then a sudden fall takes place in the activity of the former. Malic enzyme and alanine aminotransferase behave differently. Thus, the operation of the two sections of the pathway (before and after the malate step) give rise to a continuously changing functional compartmentation in the pathway. Circadian rhythmicity, on the other hand, produces time compartmentation through phase shifts and variation in amplitude, independently for each enzyme. These characteristics suggest that the operation of a so-called biological clock would be involved. We propose the hypothesis that feedback regulation would be more accurate and efficient when applied to an already oscillating, clock-controlled enzyme system.

  14. Changes in the isozymic pattern of phosphoenolpyruvate : An early step in photoperiodic control of crassulacean acid metabolism level.

    Science.gov (United States)

    Brulfert, J; Arrabaça, M C; Guerrier, D; Queiroz, O

    1979-01-01

    Two major isofunctional forms of phosphoenolpyruvate carboxylase (EC 4.1.1.31) have been separated from the leaves of Kalanchoe blossfeldiana Poelln. Tom Thumb by acrylamide gel electrophoresis and diethylaminoethyl cellulose techniques: one of the forms prevails under long-day treatment (low crassulacean acid metabolism level), the other develops under short-day treatment (high Crassulacean acid metabolism level). Molecular weights are significantly different: 175·10(3) and 186·10(3), respectively. These results indicate that two populations of phosphoenolyruvate carboxylase are present in the plant, one of which is responsible for Crassulacean acid metabolism activity under the control of photoperiod.The Crassulacean acid metabolism appears to depend on the same endogenous clock that governs other photoperiodically controlled events (e.g. flowering). The metabolic and energetic significance of this feature is discussed. It is suggested that modification in isozymic composition could be an early step in the response to photoperiodism at the metabolic level.

  15. Brain glucose sensing, glucokinase and neural control of metabolism and islet function.

    Science.gov (United States)

    Ogunnowo-Bada, E O; Heeley, N; Brochard, L; Evans, M L

    2014-09-01

    It is increasingly apparent that the brain plays a central role in metabolic homeostasis, including the maintenance of blood glucose. This is achieved by various efferent pathways from the brain to periphery, which help control hepatic glucose flux and perhaps insulin-stimulated insulin secretion. Also, critically important for the brain given its dependence on a constant supply of glucose as a fuel--emergency counter-regulatory responses are triggered by the brain if blood glucose starts to fall. To exert these control functions, the brain needs to detect rapidly and accurately changes in blood glucose. In this review, we summarize some of the mechanisms postulated to play a role in this and examine the potential role of the low-affinity hexokinase, glucokinase, in the brain as a key part of some of this sensing. We also discuss how these processes may become altered in diabetes and related metabolic diseases. © 2014 John Wiley & Sons Ltd.

  16. Hypoglycemia in pregnant women with type 1 diabetes - Predictors and role of metabolic control

    DEFF Research Database (Denmark)

    Nielsen, L.R.; Johansen, M.; Pedersen-Bjergaard, U.

    2008-01-01

    OBJECTIVE- In pregnancy with type 1 diabetes, we evaluated occurrence of mild and severe hypoglycemia and analyzed the influence of strict metabolic control, nausea, Vomiting, and other potential predictors of occurrence of severe hypoglycemia. RESEARCH DESIGN AND METHODS- A prospective...... awareness or unawareness (3.2 [1.2-8.2]) as independent predictors for severe hypoglycemia. CONCLUSIONS - In pregnancy with type 1 diabetes, the incidence of mild and severe hypoglycemia was highest in early pregnancy, although metabolic control was tighter in the last part of pregnancy. Predictors...... observational study of 108 consecutive pregnant women with type 1 diabetes was conducted. At 8, 14, 21, 27, and 33 weeks of gestation, patients performed self-monitored plasma glucose (SMPG) (eight/day) for 3 days and completed a questionnaire on nausea, vomiting, hypoglycemia awareness, and history of mild...

  17. Role of parenting style in achieving metabolic control in adolescents with type 1 diabetes.

    Science.gov (United States)

    Shorer, Maayan; David, Ravit; Schoenberg-Taz, Michal; Levavi-Lavi, Ifat; Phillip, Moshe; Meyerovitch, Joseph

    2011-08-01

    To examine the role of parenting style in achieving metabolic control and treatment adherence in adolescents with type 1 diabetes. Parents of 100 adolescents with type 1 diabetes completed assessments of their parenting style and sense of helplessness. Parents and patients rated patient adherence to the treatment regimen. Glycemic control was evaluated by HbA(1c) values. An authoritative paternal parenting style predicted better glycemic control and adherence in the child; a permissive maternal parenting style predicted poor adherence. A higher sense of helplessness in both parents predicted worse glycemic control and lesser adherence to treatment. Parental sense of helplessness was a significant predictor of diabetes control after correcting for other confounders (patient age, sex, and treatment method). An authoritative nonhelpless parenting style is associated with better diabetes control in adolescents. Paternal involvement is important in adolescent diabetes management. These results have implications for psychological interventions.

  18. Cardiovascular and metabolic syndrome risk among men with and without erectile dysfunction: case-control study

    OpenAIRE

    Zambon, João Paulo; Mendonça, Rafaela Rosalba de; Wroclawski, Marcelo Langer; Karam Junior, Amir; Santos, Raul D.; Carvalho, José Antonio Maluf de; Wroclawski, Eric Roger

    2010-01-01

    CONTEXT AND OBJECTIVE: Erectile dysfunction has been associated with cardiovascular diseases. The aim here was to evaluate cardiovascular risk through the Framingham Risk Score (FRS) criteria, C-reactive protein (CRP) assays and presence of metabolic syndrome (MS) in men with and without erectile dysfunction diagnosed within a healthcare program. DESIGN AND SETTING: A retrospective case-control study was conducted. The patients were selected from a healthcare program at the Hospital Israelita...

  19. Synthetic biology and regulatory networks: where metabolic systems biology meets control engineering.

    Science.gov (United States)

    He, Fei; Murabito, Ettore; Westerhoff, Hans V

    2016-04-01

    Metabolic pathways can be engineered to maximize the synthesis of various products of interest. With the advent of computational systems biology, this endeavour is usually carried out through in silico theoretical studies with the aim to guide and complement further in vitro and in vivo experimental efforts. Clearly, what counts is the result in vivo, not only in terms of maximal productivity but also robustness against environmental perturbations. Engineering an organism towards an increased production flux, however, often compromises that robustness. In this contribution, we review and investigate how various analytical approaches used in metabolic engineering and synthetic biology are related to concepts developed by systems and control engineering. While trade-offs between production optimality and cellular robustness have already been studied diagnostically and statically, the dynamics also matter. Integration of the dynamic design aspects of control engineering with the more diagnostic aspects of metabolic, hierarchical control and regulation analysis is leading to the new, conceptual and operational framework required for the design of robust and productive dynamic pathways. © 2016 The Author(s).

  20. Interaction of Pubertal Development and Metabolic Control in Adolescents with Type 1 Diabetes Mellitus

    Directory of Open Access Journals (Sweden)

    M. Plamper

    2017-01-01

    Full Text Available Background. In T1DM, delayed pubertal development and reduced final height are associated with inadequate metabolic control. Objective. To assess whether T1DM affects pubertal growth spurt and whether metabolic control during puberty is gender-related. Methods. Using a large multicentre database, longitudinal data from 1294 patients were analysed. Inclusion criteria: complete records of height and HbA1c from the age of seven to 16 years. Exclusion criteria: other significant chronic diseases and medications, T1DM duration less than three months, and initial BMI 97th percentile. Results. Growth velocity (GV was impaired with a significant reduction of peak GV by 1.2 cm in boys. HbA1c increase during male puberty was lower except for a period of 1.5 years. The highest HbA1c increase in boys coincided with maximum growth spurt. In girls, the highest HbA1c increase was observed during late puberty. Even though there is impaired GV, both sexes reach a height at 16 years of age which corresponds to the background population height. Conclusion. Worsening of metabolic control is sex-discordant and associated with gender-specific alterations of GV. However, the vast majority of boys and girls with T1DM seems to reach normal height at the age of 16 years.

  1. Hepatic mTORC1 controls locomotor activity, body temperature, and lipid metabolism through FGF21

    Science.gov (United States)

    Cornu, Marion; Oppliger, Wolfgang; Albert, Verena; Robitaille, Aaron M.; Trapani, Francesca; Quagliata, Luca; Fuhrer, Tobias; Sauer, Uwe; Terracciano, Luigi; Hall, Michael N.

    2014-01-01

    The liver is a key metabolic organ that controls whole-body physiology in response to nutrient availability. Mammalian target of rapamycin (mTOR) is a nutrient-activated kinase and central controller of growth and metabolism that is negatively regulated by the tumor suppressor tuberous sclerosis complex 1 (TSC1). To investigate the role of hepatic mTOR complex 1 (mTORC1) in whole-body physiology, we generated liver-specific Tsc1 (L-Tsc1 KO) knockout mice. L-Tsc1 KO mice displayed reduced locomotor activity, body temperature, and hepatic triglyceride content in a rapamycin-sensitive manner. Ectopic activation of mTORC1 also caused depletion of hepatic and plasma glutamine, leading to peroxisome proliferator–activated receptor γ coactivator-1α (PGC-1α)–dependent fibroblast growth factor 21 (FGF21) expression in the liver. Injection of glutamine or knockdown of PGC-1α or FGF21 in the liver suppressed the behavioral and metabolic defects due to mTORC1 activation. Thus, mTORC1 in the liver controls whole-body physiology through PGC-1α and FGF21. Finally, mTORC1 signaling correlated with FGF21 expression in human liver tumors, suggesting that treatment of glutamine-addicted cancers with mTOR inhibitors might have beneficial effects at both the tumor and whole-body level. PMID:25082895

  2. Procedures development and methodology of control for application of good manufacture practices (GMP) on human blood irradiation

    International Nuclear Information System (INIS)

    Boghi, Claudio

    2008-01-01

    The irradiation of human blood is used to avoid the TA-GVHD (transfusion-associated graft-versus-host-disease), a rare but devastating adverse effect of leukocytes present in blood components for a immunocompetent transfusion recipients. Usually this irradiation practice is performed to a physical elimination of leukocytes. The implementation of the procedures will assure that the properly dose in a range of 25 Gy to 50 Gy will be delivered to the blood in the bag collected in a blood tissue bank. The studies of the procedures in order to establish a GMP (Good Manufacturing Practices) were developed under the guidelines of the standard ISO 11137 - Sterilization of health care products - Requirements for validation and routine control - Radiation sterilization. In this work, two dosimetric systems were used for dose mapping during the studies of irradiator qualification, loading pattern, irradiation process validation and auditing. The CaS0 4 :Dy dosimeter presented difficulties concerning to uncertainty on dose measurement, stability, traceability and calibration. The PMMA and Gafchromic dosimetric systems have shown a better performance and were adopted on studies of irradiators qualification that are necessary to implementation of GMP. The irradiation tests have been done in a Gammacell 220 irradiator. The developed procedures can be adapted for different kinds of gamma irradiators, allowing implanting a quality assurance program and a GMP for blood irradiation. (author)

  3. Dose effects of dietary phytosterols on cholesterol metabolism: a controlled feeding study.

    Science.gov (United States)

    Racette, Susan B; Lin, Xiaobo; Lefevre, Michael; Spearie, Catherine Anderson; Most, Marlene M; Ma, Lina; Ostlund, Richard E

    2010-01-01

    Phytosterol supplementation of 2 g/d is recommended by the National Cholesterol Education Program to reduce LDL cholesterol. However, the effects of different intakes of phytosterol on cholesterol metabolism are uncertain. We evaluated the effects of 3 phytosterol intakes on whole-body cholesterol metabolism. In this placebo-controlled, crossover feeding trial, 18 adults received a phytosterol-deficient diet (50 mg phytosterols/2000 kcal) plus beverages supplemented with 0, 400, or 2000 mg phytosterols/d for 4 wk each, in random order. All meals were prepared in a metabolic kitchen; breakfast and dinner on weekdays were eaten on site. Primary outcomes were fecal cholesterol excretion and intestinal cholesterol absorption measured with stable-isotope tracers and serum lipoprotein concentrations. Phytosterol intakes (diet plus supplements) averaged 59, 459, and 2059 mg/d during the 3 diet periods. Relative to the 59-mg diet, the 459- and 2059-mg phytosterol intakes significantly (P phytosterol dose (-8.9 +/- 2.3%); a trend was observed with the 459-mg/d dose (-5.0 +/- 2.1%; P = 0.077). Dietary phytosterols in moderate and high doses favorably alter whole-body cholesterol metabolism in a dose-dependent manner. A moderate phytosterol intake (459 mg/d) can be obtained in a healthy diet without supplementation. This trial was registered at clinicaltrials.gov as NCT00860054.

  4. Dose effects of dietary phytosterols on cholesterol metabolism: a controlled feeding study123

    Science.gov (United States)

    Lin, Xiaobo; Lefevre, Michael; Spearie, Catherine Anderson; Most, Marlene M; Ma, Lina; Ostlund, Richard E

    2010-01-01

    Background: Phytosterol supplementation of 2 g/d is recommended by the National Cholesterol Education Program to reduce LDL cholesterol. However, the effects of different intakes of phytosterol on cholesterol metabolism are uncertain. Objective: We evaluated the effects of 3 phytosterol intakes on whole-body cholesterol metabolism. Design: In this placebo-controlled, crossover feeding trial, 18 adults received a phytosterol-deficient diet (50 mg phytosterols/2000 kcal) plus beverages supplemented with 0, 400, or 2000 mg phytosterols/d for 4 wk each, in random order. All meals were prepared in a metabolic kitchen; breakfast and dinner on weekdays were eaten on site. Primary outcomes were fecal cholesterol excretion and intestinal cholesterol absorption measured with stable-isotope tracers and serum lipoprotein concentrations. Results: Phytosterol intakes (diet plus supplements) averaged 59, 459, and 2059 mg/d during the 3 diet periods. Relative to the 59-mg diet, the 459- and 2059-mg phytosterol intakes significantly (P phytosterol dose (−8.9 ± 2.3%); a trend was observed with the 459-mg/d dose (−5.0 ± 2.1%; P = 0.077). Conclusions: Dietary phytosterols in moderate and high doses favorably alter whole-body cholesterol metabolism in a dose-dependent manner. A moderate phytosterol intake (459 mg/d) can be obtained in a healthy diet without supplementation. This trial was registered at clinicaltrials.gov as NCT00860054. PMID:19889819

  5. Geniposide regulates glucose-stimulated insulin secretion possibly through controlling glucose metabolism in INS-1 cells.

    Directory of Open Access Journals (Sweden)

    Jianhui Liu

    Full Text Available Glucose-stimulated insulin secretion (GSIS is essential to the control of metabolic fuel homeostasis. The impairment of GSIS is a key element of β-cell failure and one of causes of type 2 diabetes mellitus (T2DM. Although the KATP channel-dependent mechanism of GSIS has been broadly accepted for several decades, it does not fully describe the effects of glucose on insulin secretion. Emerging evidence has suggested that other mechanisms are involved. The present study demonstrated that geniposide enhanced GSIS in response to the stimulation of low or moderately high concentrations of glucose, and promoted glucose uptake and intracellular ATP levels in INS-1 cells. However, in the presence of a high concentration of glucose, geniposide exerted a contrary role on both GSIS and glucose uptake and metabolism. Furthermore, geniposide improved the impairment of GSIS in INS-1 cells challenged with a high concentration of glucose. Further experiments showed that geniposide modulated pyruvate carboxylase expression and the production of intermediates of glucose metabolism. The data collectively suggest that geniposide has potential to prevent or improve the impairment of insulin secretion in β-cells challenged with high concentrations of glucose, likely through pyruvate carboxylase mediated glucose metabolism in β-cells.

  6. Cholesterol Metabolism and Weight Reduction in Subjects with Mild Obstructive Sleep Apnoea: A Randomised, Controlled Study

    Directory of Open Access Journals (Sweden)

    Maarit Hallikainen

    2013-01-01

    Full Text Available To evaluate whether parameters of obstructive sleep apnoea (OSA associate with cholesterol metabolism before and after weight reduction, 42 middle-aged overweight subjects with mild OSA were randomised to intensive lifestyle intervention (N=23 or to control group (N=18 with routine lifestyle counselling only. Cholesterol metabolism was evaluated with serum noncholesterol sterol ratios to cholesterol, surrogate markers of cholesterol absorption (cholestanol and plant sterols and synthesis (cholestenol, desmosterol, and lathosterol at baseline and after 1-year intervention. At baseline, arterial oxygen saturation (SaO2 was associated with serum campesterol (P<0.05 and inversely with desmosterol ratios (P<0.001 independently of gender, BMI, and homeostasis model assessment index of insulin resistance (HOMA-IR. Apnoea-hypopnoea index (AHI was not associated with cholesterol metabolism. Weight reduction significantly increased SaO2and serum cholestanol and decreased AHI and serum cholestenol ratios. In the groups combined, the changes in AHI were inversely associated with changes of cholestanol and positively with cholestenol ratios independent of gender and the changes of BMI and HOMA-IR (P<0.05. In conclusion, mild OSA seemed to be associated with cholesterol metabolism independent of BMI and HOMA-IR. Weight reduction increased the markers of cholesterol absorption and decreased those of cholesterol synthesis in the overweight subjects with mild OSA.

  7. Effects of TCMC on Transformation of Good Health Status to Suboptimal Health Status: A Nested Case-Control Study

    Science.gov (United States)

    Wang, Tian; Chen, Jieyu; Sun, Xiaomin; Xiang, Lei; Zhou, Lin; Li, Fei; Lin, Changsong; Jiang, Pingping; Wu, Shengwei; Xiao, Ya; Cheng, Jingru; Luo, Ren; Liu, Yanyan; Zhao, Xiaoshan

    2015-01-01

    To explore the effects of traditional Chinese medicine constitution (TCMC) on transformation of good health status to suboptimal health status (SHS), we conducted a nested case-control study among college students in China. During the 18-month mean follow-up time, 543 cases of SHS (42.7%) occurred in 1273 healthy students. There was a significant (P = 0.000) and marked reduction in SHMS V1.0 total score in the case group at the 18-month follow-up (69.32 ± 5.45) compared with baseline (78.60 ± 4.70), but there was no significant change in the control group. Conditional logistic regression analysis showed that respondents reporting Yin-deficiency and Qi-deficiency were, respectively, 2.247 and 2.198 times more likely to develop SHS, while tendency to Yin-deficiency and tendency to Damp-heat were, respectively, 1.642 and 1.506 times more likely to develop SHS. However, the Balanced Constitution was a significant protective factor (OR 0.649; P < 0.05). Altogether, these findings demonstrate that Yin-deficiency, Qi-deficiency, tendency to Yin-deficiency, and tendency to Damp-heat appeared to induce a change in health status to SHS, while the Balanced Constitution seemed to restrain this change. We conclude that regulating the unbalanced TCMC (such as Yin-deficiency and Qi-deficiency) may prevent a healthy status developing into SHS or lead to the regression of SHS. PMID:26346320

  8. Effects of TCMC on Transformation of Good Health Status to Suboptimal Health Status: A Nested Case-Control Study

    Directory of Open Access Journals (Sweden)

    Tian Wang

    2015-01-01

    Full Text Available To explore the effects of traditional Chinese medicine constitution (TCMC on transformation of good health status to suboptimal health status (SHS, we conducted a nested case-control study among college students in China. During the 18-month mean follow-up time, 543 cases of SHS (42.7% occurred in 1273 healthy students. There was a significant (P=0.000 and marked reduction in SHMS V1.0 total score in the case group at the 18-month follow-up (69.32 ± 5.45 compared with baseline (78.60 ± 4.70, but there was no significant change in the control group. Conditional logistic regression analysis showed that respondents reporting Yin-deficiency and Qi-deficiency were, respectively, 2.247 and 2.198 times more likely to develop SHS, while tendency to Yin-deficiency and tendency to Damp-heat were, respectively, 1.642 and 1.506 times more likely to develop SHS. However, the Balanced Constitution was a significant protective factor (OR 0.649; P<0.05. Altogether, these findings demonstrate that Yin-deficiency, Qi-deficiency, tendency to Yin-deficiency, and tendency to Damp-heat appeared to induce a change in health status to SHS, while the Balanced Constitution seemed to restrain this change. We conclude that regulating the unbalanced TCMC (such as Yin-deficiency and Qi-deficiency may prevent a healthy status developing into SHS or lead to the regression of SHS.

  9. Accidental goodness?

    DEFF Research Database (Denmark)

    Richter, Anne

    In postmodern capitalist market economies, management of the single organisation is bound to be guided by several rationales, which are in conflict with each other. For some writers this perception leads to the argument, that conceptions of management should strive towards goals beyond the present...... society. For others, the handling of plural perspectives is just a management discipline. However these positions seem to share a focus on organization as a the arena for the organization of the good. The contribution looks at the management of occupational accidents as an example of striving for good...

  10. A soft sensor for bioprocess control based on sequential filtering of metabolic heat signals.

    Science.gov (United States)

    Paulsson, Dan; Gustavsson, Robert; Mandenius, Carl-Fredrik

    2014-09-26

    Soft sensors are the combination of robust on-line sensor signals with mathematical models for deriving additional process information. Here, we apply this principle to a microbial recombinant protein production process in a bioreactor by exploiting bio-calorimetric methodology. Temperature sensor signals from the cooling system of the bioreactor were used for estimating the metabolic heat of the microbial culture and from that the specific growth rate and active biomass concentration were derived. By applying sequential digital signal filtering, the soft sensor was made more robust for industrial practice with cultures generating low metabolic heat in environments with high noise level. The estimated specific growth rate signal obtained from the three stage sequential filter allowed controlled feeding of substrate during the fed-batch phase of the production process. The biomass and growth rate estimates from the soft sensor were also compared with an alternative sensor probe and a capacitance on-line sensor, for the same variables. The comparison showed similar or better sensitivity and lower variability for the metabolic heat soft sensor suggesting that using permanent temperature sensors of a bioreactor is a realistic and inexpensive alternative for monitoring and control. However, both alternatives are easy to implement in a soft sensor, alone or in parallel.

  11. A Soft Sensor for Bioprocess Control Based on Sequential Filtering of Metabolic Heat Signals

    Directory of Open Access Journals (Sweden)

    Dan Paulsson

    2014-09-01

    Full Text Available Soft sensors are the combination of robust on-line sensor signals with mathematical models for deriving additional process information. Here, we apply this principle to a microbial recombinant protein production process in a bioreactor by exploiting bio-calorimetric methodology. Temperature sensor signals from the cooling system of the bioreactor were used for estimating the metabolic heat of the microbial culture and from that the specific growth rate and active biomass concentration were derived. By applying sequential digital signal filtering, the soft sensor was made more robust for industrial practice with cultures generating low metabolic heat in environments with high noise level. The estimated specific growth rate signal obtained from the three stage sequential filter allowed controlled feeding of substrate during the fed-batch phase of the production process. The biomass and growth rate estimates from the soft sensor were also compared with an alternative sensor probe and a capacitance on-line sensor, for the same variables. The comparison showed similar or better sensitivity and lower variability for the metabolic heat soft sensor suggesting that using permanent temperature sensors of a bioreactor is a realistic and inexpensive alternative for monitoring and control. However, both alternatives are easy to implement in a soft sensor, alone or in parallel.

  12. Metabolic control over the oxygen consumption flux in intact skeletal muscle: in silico studies.

    Science.gov (United States)

    Liguzinski, Piotr; Korzeniewski, Bernard

    2006-12-01

    It has been postulated previously that a direct activation of all oxidative phosphorylation complexes in parallel with the activation of ATP usage and substrate dehydrogenation (the so-called each-step activation) is the main mechanism responsible for adjusting the rate of ATP production by mitochondria to the current energy demand during rest-to-work transition in intact skeletal muscle in vivo. The present in silico study, using a computer model of oxidative phosphorylation developed previously, analyzes the impact of the each-step-activation mechanism on the distribution of control (defined within Metabolic Control Analysis) over the oxygen consumption flux among the components of the bioenergetic system in intact oxidative skeletal muscle at different energy demands. It is demonstrated that in the absence of each-step activation, the oxidative phosphorylation complexes take over from ATP usage most of the control over the respiration rate and oxidative ATP production at higher (but still physiological) energy demands. This leads to a saturation of oxidative phosphorylation, impossibility of a further acceleration of oxidative ATP synthesis, and dramatic drop in the phosphorylation potential. On the other hand, the each-step-activation mechanism allows maintenance of a high degree of the control exerted by ATP usage over the ATP turnover and oxygen consumption flux even at high energy demands and thus enables a potentially very large increase in ATP turnover. It is also shown that low oxygen concentration shifts the metabolic control from ATP usage to cytochrome oxidase and thus limits the oxidative ATP production.

  13. Risk of metabolic syndrome among children living in metropolitan Kuala Lumpur: A case control study

    Directory of Open Access Journals (Sweden)

    Ismail Mohd N

    2011-05-01

    Full Text Available Abstract Background With the increasing prevalence of childhood obesity, the metabolic syndrome has been studied among children in many countries but not in Malaysia. Hence, this study aimed to compare metabolic risk factors between overweight/obese and normal weight children and to determine the influence of gender and ethnicity on the metabolic syndrome among school children aged 9-12 years in Kuala Lumpur and its metropolitan suburbs. Methods A case control study was conducted among 402 children, comprising 193 normal-weight and 209 overweight/obese. Weight, height, waist circumference (WC and body composition were measured, and WHO (2007 growth reference was used to categorise children into the two weight groups. Blood pressure (BP was taken, and blood was drawn after an overnight fast to determine fasting blood glucose (FBG and full lipid profile, including triglycerides (TG, high-density lipoprotein cholesterol (HDL-C, low-density lipoprotein cholesterol (LDL-C and total cholesterol (TC. International Diabetes Federation (2007 criteria for children were used to identify metabolic syndrome. Results Participants comprised 60.9% (n = 245 Malay, 30.9% (n = 124 Chinese and 8.2% (n = 33 Indian. Overweight/obese children showed significantly poorer biochemical profile, higher body fat percentage and anthropometric characteristics compared to the normal-weight group. Among the metabolic risk factors, WC ≥90th percentile was found to have the highest odds (OR = 189.0; 95%CI 70.8, 504.8, followed by HDL-C≤1.03 mmol/L (OR = 5.0; 95%CI 2.4, 11.1 and high BP (OR = 4.2; 95%CI 1.3, 18.7. Metabolic syndrome was found in 5.3% of the overweight/obese children but none of the normal-weight children (p Conclusions We conclude that being overweight or obese poses a greater risk of developing the metabolic syndrome among children. Indian ethnicity is at higher risk compared to their counterparts of the same age. Hence, primary intervention strategies are

  14. Effect of oral cinnamon intervention on metabolic profile and body composition of Asian Indians with metabolic syndrome: a randomized double -blind control trial.

    Science.gov (United States)

    Gupta Jain, Sonal; Puri, Seema; Misra, Anoop; Gulati, Seema; Mani, Kalaivani

    2017-06-12

    Nutritional modulation remains central to the management of metabolic syndrome. Intervention with cinnamon in individuals with metabolic syndrome remains sparsely researched. We investigated the effect of oral cinnamon consumption on body composition and metabolic parameters of Asian Indians with metabolic syndrome. In this 16-week double blind randomized control trial, 116 individuals with metabolic syndrome were randomized to two dietary intervention groups, cinnamon [6 capsules (3 g) daily] or wheat flour [6 capsules (2.5 g) daily]. Body composition, blood pressure and metabolic parameters were assessed. Significantly greater decrease [difference between means, (95% CI)] in fasting blood glucose (mmol/L) [0.3 (0.2, 0.5) p = 0.001], glycosylated haemoglobin (mmol/mol) [2.6 (0.4, 4.9) p = 0.023], waist circumference (cm) [4.8 (1.9, 7.7) p = 0.002] and body mass index (kg/m2 ) [1.3 (0.9, 1.5) p = 0.001] was observed in the cinnamon group compared to placebo group. Other parameters which showed significantly greater improvement were: waist-hip ratio, blood pressure, serum total cholesterol, low-density lipoprotein cholesterol, serum triglycerides, and high-density lipoprotein cholesterol. Prevalence of defined metabolic syndrome was significantly reduced in the intervention group (34.5%) vs. the placebo group (5.2%). A single supplement intervention with 3 g cinnamon for 16 weeks resulted in significant improvements in all components of metabolic syndrome in a sample of Asian Indians in north India. The clinical trial was retrospectively registered (after the recruitment of the participants) in ClinicalTrial.gov under the identification number: NCT02455778 on 25th May 2015.

  15. Good Faith

    DEFF Research Database (Denmark)

    Fomcenco, Alex

    2017-01-01

    This article outlines the current state of law in Canada in respect to good faith in contratial relations. The topic is highly relevant due to expected growth in the numbers of contracts concluded between European and Canadian enterprises in the wake of adoption of the Comprehensive Economic...

  16. Longitudinal Trajectories of Metabolic Control across Adolescence: Associations with Parental Involvement, Adolescents’ Psychosocial Maturity, and Health Care Utilization

    Science.gov (United States)

    King, Pamela S.; Berg, Cynthia A.; Butner, Jonathan; Drew, Linda M.; Foster, Carol; Donaldson, David; Murray, Mary; Swinyard, Michael; Wiebe, Deborah J.

    2012-01-01

    Purpose To predict trajectories of metabolic control across adolescence from parental involvement and adolescent psychosocial maturity, and to link metabolic control trajectories to health care utilization. Methods 252 adolescents (M age at study initiation = 12.5, SD=1.5, range 10–14 years) with type 1 diabetes (54.4% female, 92.8% Caucasian, length of diagnosis M=4.7 years, SD=3.0, range 1–12) participated in a 2-year longitudinal study. Metabolic control was gathered from medical records every three months. Adolescents completed measures of self-reliance (functional autonomy and extreme peer orientation), self-control (self-control and externalizing behavior), and parental involvement in diabetes care (acceptance, monitoring, and frequency of help). At the end of the study, mothers reported health care utilization (diabetes-related emergency room visits and hospitalizations) over the past six months. Results Latent class growth analyses indicated two distinct trajectories of metabolic control across adolescence: moderate control with slight deterioration (92% of the sample; average HbA1c = 8.18%) and poor control with rapid deterioration (8% of the sample; average HbA1c of 12.09%). Adolescents with poor and rapidly deteriorating metabolic control reported lower paternal monitoring and frequency of help with diabetes management, lower functional autonomy, and lower self-control than others. Those with poor and rapidly deteriorating metabolic control were 6.4 times more likely to report diabetes-related emergency room visits, and 9.3 times more likely to report diabetes-related hospitalizations near the end of the study. Conclusions Parental involvement and adolescents’ psychosocial maturity predict patterns of deteriorating metabolic control across adolescence and could be targeted for intervention. PMID:22525113

  17. Analysis of clock-regulated genes in Neurospora reveals widespread posttranscriptional control of metabolic potential

    Science.gov (United States)

    Hurley, Jennifer M.; Dasgupta, Arko; Emerson, Jillian M.; Zhou, Xiaoying; Ringelberg, Carol S.; Knabe, Nicole; Lipzen, Anna M.; Lindquist, Erika A.; Daum, Christopher G.; Barry, Kerrie W.; Grigoriev, Igor V.; Smith, Kristina M.; Galagan, James E.; Bell-Pedersen, Deborah; Freitag, Michael; Cheng, Chao; Loros, Jennifer J.; Dunlap, Jay C.

    2014-01-01

    Neurospora crassa has been for decades a principal model for filamentous fungal genetics and physiology as well as for understanding the mechanism of circadian clocks. Eukaryotic fungal and animal clocks comprise transcription-translation–based feedback loops that control rhythmic transcription of a substantial fraction of these transcriptomes, yielding the changes in protein abundance that mediate circadian regulation of physiology and metabolism: Understanding circadian control of gene expression is key to understanding eukaryotic, including fungal, physiology. Indeed, the isolation of clock-controlled genes (ccgs) was pioneered in Neurospora where circadian output begins with binding of the core circadian transcription factor WCC to a subset of ccg promoters, including those of many transcription factors. High temporal resolution (2-h) sampling over 48 h using RNA sequencing (RNA-Seq) identified circadianly expressed genes in Neurospora, revealing that from ∼10% to as much 40% of the transcriptome can be expressed under circadian control. Functional classifications of these genes revealed strong enrichment in pathways involving metabolism, protein synthesis, and stress responses; in broad terms, daytime metabolic potential favors catabolism, energy production, and precursor assembly, whereas night activities favor biosynthesis of cellular components and growth. Discriminative regular expression motif elicitation (DREME) identified key promoter motifs highly correlated with the temporal regulation of ccgs. Correlations between ccg abundance from RNA-Seq, the degree of ccg-promoter activation as reported by ccg-promoter–luciferase fusions, and binding of WCC as measured by ChIP-Seq, are not strong. Therefore, although circadian activation is critical to ccg rhythmicity, posttranscriptional regulation plays a major role in determining rhythmicity at the mRNA level. PMID:25362047

  18. LA sprouts randomized controlled nutrition and gardening program reduces obesity and metabolic risk in Latino youth.

    Science.gov (United States)

    Gatto, Nicole M; Martinez, Lauren C; Spruijt-Metz, Donna; Davis, Jaimie N

    2015-06-01

    To assess the effects of a 12-week gardening, nutrition, and cooking intervention ("LA Sprouts") on dietary intake, obesity parameters, and metabolic disease risk among low-income, primarily Hispanic/Latino youth in Los Angeles. The randomized controlled trial involved four elementary schools [two schools randomized to intervention (172 third-through fifth-grade students); two schools randomized to control (147 third-through fifth-grade students)]. Classes were taught in 90-minute sessions once a week to each grade level for 12 weeks. Data collected at pre- and postintervention included dietary intake via food frequency questionnaire (FFQ), anthropometric measures [BMI, waist circumference (WC)], body fat, and fasting blood samples. LA Sprouts participants had significantly greater reductions in BMI z-scores (0.1-vs. 0.04-point decrease, respectively; P = 0.01) and WC (-1.2 cm vs. no change; P < 0.001). Fewer LA Sprouts participants had the metabolic syndrome (MetSyn) after the intervention than before, while the number of controls with MetSyn increased. LA Sprouts participants had improvements in dietary fiber intake (+3.5% vs. -15.5%; P = 0.04) and less decreases in vegetable intake (-3.6% vs. -26.4%; P = 0.04). Change in fruit intake before and after the intervention did not significantly differ between LA Sprouts and control subjects. LA Sprouts was effective in reducing obesity and metabolic risk. © 2015 The Obesity Society.

  19. A structured approach to the study of metabolic control principles in intact and impaired mitochondria.

    Science.gov (United States)

    Huber, Heinrich J; Connolly, Niamh M C; Dussmann, Heiko; Prehn, Jochen H M

    2012-03-01

    We devised an approach to extract control principles of cellular bioenergetics for intact and impaired mitochondria from ODE-based models and applied it to a recently established bioenergetic model of cancer cells. The approach used two methods for varying ODE model parameters to determine those model components that, either alone or in combination with other components, most decisively regulated bioenergetic state variables. We found that, while polarisation of the mitochondrial membrane potential (ΔΨ(m)) and, therefore, the protomotive force were critically determined by respiratory complex I activity in healthy mitochondria, complex III activity was dominant for ΔΨ(m) during conditions of cytochrome-c deficiency. As a further important result, cellular bioenergetics in healthy, ATP-producing mitochondria was regulated by three parameter clusters that describe (1) mitochondrial respiration, (2) ATP production and consumption and (3) coupling of ATP-production and respiration. These parameter clusters resembled metabolic blocks and their intermediaries from top-down control analyses. However, parameter clusters changed significantly when cells changed from low to high ATP levels or when mitochondria were considered to be impaired by loss of cytochrome-c. This change suggests that the assumption of static metabolic blocks by conventional top-down control analyses is not valid under these conditions. Our approach is complementary to both ODE and top-down control analysis approaches and allows a better insight into cellular bioenergetics and its pathological alterations.

  20. Thyroid peroxidase antibodies in pregnant women with type 1 diabetes: impact on thyroid function, metabolic control and pregnancy outcome

    DEFF Research Database (Denmark)

    Vestgaard, Marianne; Nielsen, Lene Ringholm; Rasmussen, Åse Krogh

    2008-01-01

    In pregnant women with type 1 diabetes, we evaluated whether the presence of thyroid peroxidase autoantibodies (anti-TPO) was associated with changes in thyroid function, metabolic control and pregnancy outcome....

  1. Comparing metabolic control and complications in type 2 diabetes in two Pacific Islands at baseline and following diabetes care intervention

    Directory of Open Access Journals (Sweden)

    Si Thu Win Tin

    2016-06-01

    Conclusions: This study indicates improved metabolic control but little change in diabetes complications 15 months after intervention. Efforts to improve and evaluate the ongoing quality and accessibility of diabetes care in Pacific Island settings need to be further strengthened.

  2. Knowledge, compliance with good clinical practices and barriers to effective control of postoperative pain among nurses from hospitals with and without a "Hospital without Pain" certificate.

    Science.gov (United States)

    Tomaszek, Lucyna; Dębska, Grażyna

    2018-04-01

    (i) To compare knowledge and compliance with good clinical practices regarding control of postoperative pain among nurses employed at hospitals with and without a "Hospital without Pain" certificate, (ii) to identify the determinants of nurses' knowledge and (iii) to define barriers to effective control of postoperative pain. Only a slight improvement in postoperative pain control has been observed recently, if any. Implementation of good clinical practices in the control of postoperative pain requires involvement of nurses. A cross-sectional study. The study included 257 nurses from hospitals with a "Hospital without Pain" certificate and 243 nurses from noncertified hospitals, with mean job seniority of 17.6 ± 9.6 years. All respondents answered 26 questions regarding postoperative pain control-related issues. Based on the answers, overall scores were calculated for (i) nurses' knowledge, (ii) compliance with good clinical practices and (iii) barriers to effective control of postoperative pain. Nurses from the certified hospitals presented with significantly higher levels of knowledge and compliance with good clinical practices and identified significantly more barriers to effective control of postoperative pain. Apart from certification of a hospital, better knowledge of postoperative pain control was determined by higher education, participation in postgraduate training programmes and other relevant courses, self-education from medical journals, employment at paediatric ward or intensive care unit. The most commonly reported barriers to effective control of pain included too low doses of painkillers prescribed by physicians and inability to modify the protocol of pain treatment by the nurse. Control of postoperative pain can be improved by enrolling nurses in various forms of continuous training and by providing them with greater autonomy in administering painkillers to surgical patients. Better quality of care offered to patients with postoperative pain

  3. Linking metabolic QTLs with network and cis-eQTLs controlling biosynthetic pathways.

    Directory of Open Access Journals (Sweden)

    Adam M Wentzell

    2007-09-01

    Full Text Available Phenotypic variation between individuals of a species is often under quantitative genetic control. Genomic analysis of gene expression polymorphisms between individuals is rapidly gaining popularity as a way to query the underlying mechanistic causes of variation between individuals. However, there is little direct evidence of a linkage between global gene expression polymorphisms and phenotypic consequences. In this report, we have mapped quantitative trait loci (QTLs-controlling glucosinolate content in a population of 403 Arabidopsis Bay x Sha recombinant inbred lines, 211 of which were previously used to identify expression QTLs controlling the transcript levels of biosynthetic genes. In a comparative study, we have directly tested two plant biosynthetic pathways for association between polymorphisms controlling biosynthetic gene transcripts and the resulting metabolites within the Arabidopsis Bay x Sha recombinant inbred line population. In this analysis, all loci controlling expression variation also affected the accumulation of the resulting metabolites. In addition, epistasis was detected more frequently for metabolic traits compared to transcript traits, even when both traits showed similar distributions. An analysis of candidate genes for QTL-controlling networks of transcripts and metabolites suggested that the controlling factors are a mix of enzymes and regulatory factors. This analysis showed that regulatory connections can feedback from metabolism to transcripts. Surprisingly, the most likely major regulator of both transcript level for nearly the entire pathway and aliphatic glucosinolate accumulation is variation in the last enzyme in the biosynthetic pathway, AOP2. This suggests that natural variation in transcripts may significantly impact phenotypic variation, but that natural variation in metabolites or their enzymatic loci can feed back to affect the transcripts.

  4. Effects of pistachio nuts on body composition, metabolic, inflammatory and oxidative stress parameters in Asian Indians with metabolic syndrome: a 24-wk, randomized control trial.

    Science.gov (United States)

    Gulati, Seema; Misra, Anoop; Pandey, Ravindra Mohan; Bhatt, Surya Prakash; Saluja, Shelza

    2014-02-01

    The aim of this study was to evaluate the effects of pistachio nuts as an adjunct to diet and exercise on body composition, metabolic, inflammatory, and oxidative stress parameters in Asian Indians with metabolic syndrome. In this 24-wk randomized control trial, 60 individuals with the metabolic syndrome were randomized to either pistachio (intervention group) or control group (diet as per weight and physical activity profile, modulated according to dietary guidelines for Asian Indians) after 3 wk of a diet and exercise run in. In the first group, unsalted pistachios (20% energy) were given daily. A standard diet and exercise protocol was followed for both groups. Body weight, waist circumference (WC), magnetic resonance imaging estimation of intraabdominal adipose tissue and subcutaneous abdominal adipose tissue, fasting blood glucose (FBG), fasting serum insulin, glycosylated hemoglobin, lipid profile, high-sensitivity C-reactive protein (hs-CRP), adiponectin, free fatty acids (FFAs), tumor necrosis factor (TNF)-α, leptin, and thiobarbituric acid reactive substances (TBARS) were assessed before and after the intervention. Statistically significant improvement in mean values for various parameters in the intervention group compared with control group were as follows: WC (P pistachios leads to beneficial effects on the cardiometabolic profile of Asian Indians with metabolic syndrome. Copyright © 2014 Elsevier Inc. All rights reserved.

  5. Locomotor Adaptation Improves Balance Control, Multitasking Ability and Reduces the Metabolic Cost of Postural Instability

    Science.gov (United States)

    Bloomberg, J. J.; Peters, B. T.; Mulavara, A. P.; Brady, R. A.; Batson, C. D.; Miller, C. A.; Ploutz-Snyder, R. J.; Guined, J. R.; Buxton, R. E.; Cohen, H. S.

    2011-01-01

    During exploration-class missions, sensorimotor disturbances may lead to disruption in the ability to ambulate and perform functional tasks during the initial introduction to a novel gravitational environment following a landing on a planetary surface. The overall goal of our current project is to develop a sensorimotor adaptability training program to facilitate rapid adaptation to these environments. We have developed a unique training system comprised of a treadmill placed on a motion-base facing a virtual visual scene. It provides an unstable walking surface combined with incongruent visual flow designed to enhance sensorimotor adaptability. Greater metabolic cost incurred during balance instability means more physical work is required during adaptation to new environments possibly affecting crewmembers? ability to perform mission critical tasks during early surface operations on planetary expeditions. The goal of this study was to characterize adaptation to a discordant sensory challenge across a number of performance modalities including locomotor stability, multi-tasking ability and metabolic cost. METHODS: Subjects (n=15) walked (4.0 km/h) on a treadmill for an 8 -minute baseline walking period followed by 20-minutes of walking (4.0 km/h) with support surface motion (0.3 Hz, sinusoidal lateral motion, peak amplitude 25.4 cm) provided by the treadmill/motion-base system. Stride frequency and auditory reaction time were collected as measures of locomotor stability and multi-tasking ability, respectively. Metabolic data (VO2) were collected via a portable metabolic gas analysis system. RESULTS: At the onset of lateral support surface motion, subj ects walking on our treadmill showed an increase in stride frequency and auditory reaction time indicating initial balance and multi-tasking disturbances. During the 20-minute adaptation period, balance control and multi-tasking performance improved. Similarly, throughout the 20-minute adaptation period, VO2 gradually

  6. Brain PET substrate of impulse control disorders in Parkinson's disease: A metabolic connectivity study.

    Science.gov (United States)

    Verger, Antoine; Klesse, Elsa; Chawki, Mohammad B; Witjas, Tatiana; Azulay, Jean-Philippe; Eusebio, Alexandre; Guedj, Eric

    2018-04-10

    Impulse control disorders (ICDs) have received increased attention in Parkinson's disease (PD) because of potentially dramatic consequences. Their physiopathology, however, remains incompletely understood. An overstimulation of the mesocorticolimbic system has been reported, while a larger network has recently been suggested. The aim of this study is to specifically describe the metabolic PET substrate and related connectivity changes in PD patients with ICDs. Eighteen PD patients with ICDs and 18 PD patients without ICDs were evaluated using cerebral 18F-fluorodeoxyglucose positron emission tomography. SPM-T maps comparisons were performed between groups and metabolic connectivity was evaluated by interregional correlation analysis (IRCA; p  130) and by graph theory (p < .05). PD patients with ICDs had relative increased metabolism in the right middle and inferior temporal gyri compared to those without ICDs. The connectivity of this area was increased mostly with the mesocorticolimbic system, positively with the orbitofrontal region, and negatively with both the right parahippocampus and the left caudate (IRCA). Moreover, the betweenness centrality of this area with the mesocorticolimbic system was lost in patients with ICDs (graph analysis). ICDs are associated in PD with the dysfunction of a network exceeding the mesocorticolimbic system, and especially the caudate, the parahippocampus, and the orbitofrontal cortex, remotely including the right middle and inferior temporal gyri. This latest area loses its central place with the mesocorticolimbic system through a connectivity dysregulation. © 2018 Wiley Periodicals, Inc.

  7. Muscle insulin sensitivity and glucose metabolism are controlled by the intrinsic muscle clock★

    Science.gov (United States)

    Dyar, Kenneth A.; Ciciliot, Stefano; Wright, Lauren E.; Biensø, Rasmus S.; Tagliazucchi, Guidantonio M.; Patel, Vishal R.; Forcato, Mattia; Paz, Marcia I.P.; Gudiksen, Anders; Solagna, Francesca; Albiero, Mattia; Moretti, Irene; Eckel-Mahan, Kristin L.; Baldi, Pierre; Sassone-Corsi, Paolo; Rizzuto, Rosario; Bicciato, Silvio; Pilegaard, Henriette; Blaauw, Bert; Schiaffino, Stefano

    2013-01-01

    Circadian rhythms control metabolism and energy homeostasis, but the role of the skeletal muscle clock has never been explored. We generated conditional and inducible mouse lines with muscle-specific ablation of the core clock gene Bmal1. Skeletal muscles from these mice showed impaired insulin-stimulated glucose uptake with reduced protein levels of GLUT4, the insulin-dependent glucose transporter, and TBC1D1, a Rab-GTPase involved in GLUT4 translocation. Pyruvate dehydrogenase (PDH) activity was also reduced due to altered expression of circadian genes Pdk4 and Pdp1, coding for PDH kinase and phosphatase, respectively. PDH inhibition leads to reduced glucose oxidation and diversion of glycolytic intermediates to alternative metabolic pathways, as revealed by metabolome analysis. The impaired glucose metabolism induced by muscle-specific Bmal1 knockout suggests that a major physiological role of the muscle clock is to prepare for the transition from the rest/fasting phase to the active/feeding phase, when glucose becomes the predominant fuel for skeletal muscle. PMID:24567902

  8. A Transcript-Specific eIF3 Complex Mediates Global Translational Control of Energy Metabolism.

    Science.gov (United States)

    Shah, Meera; Su, Dan; Scheliga, Judith S; Pluskal, Tomáš; Boronat, Susanna; Motamedchaboki, Khatereh; Campos, Alexandre Rosa; Qi, Feng; Hidalgo, Elena; Yanagida, Mitsuhiro; Wolf, Dieter A

    2016-08-16

    The multi-subunit eukaryotic translation initiation factor eIF3 is thought to assist in the recruitment of ribosomes to mRNA. The expression of eIF3 subunits is frequently disrupted in human cancers, but the specific roles of individual subunits in mRNA translation and cancer remain elusive. Using global transcriptomic, proteomic, and metabolomic profiling, we found a striking failure of Schizosaccharomyces pombe cells lacking eIF3e and eIF3d to synthesize components of the mitochondrial electron transport chain, leading to a defect in respiration, endogenous oxidative stress, and premature aging. Energy balance was maintained, however, by a switch to glycolysis with increased glucose uptake, upregulation of glycolytic enzymes, and strict dependence on a fermentable carbon source. This metabolic regulatory function appears to be conserved in human cells where eIF3e binds metabolic mRNAs and promotes their translation. Thus, via its eIF3d-eIF3e module, eIF3 orchestrates an mRNA-specific translational mechanism controlling energy metabolism that may be disrupted in cancer. Copyright © 2016 The Author(s). Published by Elsevier Inc. All rights reserved.

  9. α/β-Hydrolase Domain 6 in the Ventromedial Hypothalamus Controls Energy Metabolism Flexibility

    Directory of Open Access Journals (Sweden)

    Alexandre Fisette

    2016-10-01

    Full Text Available α/β-Hydrolase domain 6 (ABHD6 is a monoacylglycerol hydrolase that degrades the endocannabinoid 2-arachidonoylglycerol (2-AG. Although complete or peripheral ABHD6 loss of function is protective against diet-induced obesity and insulin resistance, the role of ABHD6 in the central control of energy balance is unknown. Using a viral-mediated knockout approach, targeted endocannabinoid measures, and pharmacology, we discovered that mice lacking ABHD6 from neurons of the ventromedial hypothalamus (VMHKO have higher VMH 2-AG levels in conditions of endocannabinoid recruitment and fail to physiologically adapt to key metabolic challenges. VMHKO mice exhibited blunted fasting-induced feeding and reduced food intake, energy expenditure, and adaptive thermogenesis in response to cold exposure, high-fat feeding, and dieting (transition to a low-fat diet. Our findings identify ABHD6 as a regulator of the counter-regulatory responses to major metabolic shifts, including fasting, nutrient excess, cold, and dieting, thereby highlighting the importance of ABHD6 in the VMH in mediating energy metabolism flexibility.

  10. A Transcript-Specific eIF3 Complex Mediates Global Translational Control of Energy Metabolism

    Directory of Open Access Journals (Sweden)

    Meera Shah

    2016-08-01

    Full Text Available The multi-subunit eukaryotic translation initiation factor eIF3 is thought to assist in the recruitment of ribosomes to mRNA. The expression of eIF3 subunits is frequently disrupted in human cancers, but the specific roles of individual subunits in mRNA translation and cancer remain elusive. Using global transcriptomic, proteomic, and metabolomic profiling, we found a striking failure of Schizosaccharomyces pombe cells lacking eIF3e and eIF3d to synthesize components of the mitochondrial electron transport chain, leading to a defect in respiration, endogenous oxidative stress, and premature aging. Energy balance was maintained, however, by a switch to glycolysis with increased glucose uptake, upregulation of glycolytic enzymes, and strict dependence on a fermentable carbon source. This metabolic regulatory function appears to be conserved in human cells where eIF3e binds metabolic mRNAs and promotes their translation. Thus, via its eIF3d-eIF3e module, eIF3 orchestrates an mRNA-specific translational mechanism controlling energy metabolism that may be disrupted in cancer.

  11. [DiabeTIC website: a pilot study of satisfaction and impact on metabolic control].

    Science.gov (United States)

    Carral San Laureano, Florentino; Ayala Ortega, María del Carmen; Jiménez Millán, Ana Isabel; Piñero Zaldivar, Antonia; García Calzado, Concepción; Prieto Ferrón, Matilde; Silva Rodríguez, Juan José

    2013-10-01

    To evaluate satisfaction and short-term impact on metabolic control of diabetes monitoring through the DiabeTIC website. A prospective, uncontrolled intervention study was conducted in 32 patients aged 29.7±9.7 years (65% female) incorporated to the telemedicine platform DiabeTIC between March and September 2012. All patients completed a satisfaction questionnaire in the first month, and impact on metabolic control was evaluated at three and six months. In the satisfaction survey conducted in the first month of follow-up, the following mean scores (0-10) were obtained: overall impression with the platform: 8.6±1.8; ease of use: 8.1±1.5; intuitive navigation: 6.7±3.0; value of measurements: 9.1±1.1; importance of the platform in diabetes management: 9.5±0.9; sense of security: 9.5±0.8; value of the library: 9.4±1.1; value of messages: 9.1±1.4, and recommendation to use the platform: 9.4±0.9. Glycosilated hemoglobin concentrations significantly improved at six months as compared to study start (7.0±0.8 versus 8.1±1.9; p=0.007). Nine patients were discharged from DiabeTIC before completing six months of follow-up. Patients with diabetes monitored through the DiabeTIC website report a high degree of satisfaction, showing improved metabolic control at short-term follow-up. Copyright © 2012 SEEN. Published by Elsevier Espana. All rights reserved.

  12. Metabolic Correction in the Management of Diabetic Peripheral Neuropathy: Improving Clinical Results Beyond Symptom Control

    Science.gov (United States)

    Miranda-Massari, Jorge R.; Gonzalez, Michael J.; Jimenez, Francisco J.; Allende-Vigo, Myriam Z.; Duconge, Jorge

    2013-01-01

    Current Clinical Management Guidelines of Diabetic Peripheral Neuropathy (DPN) are based on adequate glucose control and symptomatic pain relief. However, meticulous glycemic control could delay the onset or slow the progression of diabetic neuropathy in patients with DM type 2, but it does not completely prevent the progression of the disease. Complications of DPN as it continues its natural course, produce increasing pain and discomfort, loss of sensation, ulcers, infections, amputations and even death. In addition to the increased suffering, disability and loss of productivity, there is a very significant economic impact related to the treatment of DPN and its complications. In USA alone, it has been estimated that there are more than 5,000,000 patients suffering from DPN and the total annual cost of treating the disease and its complications is over $10,000 million dollars. In order to be able to reduce complications of DPN, it is crucial to improve or correct the metabolic conditions that lead to the pathology present in this condition. Pathophysiologic mechanisms implicated in diabetic neuropathy include: increased polyol pathway with accumulation of sorbitol and reduced Na+/K+-ATPase activity, microvascular damage and hypoxia due to nitric oxide deficit and increased oxygen free radical activity. Moreover, there is a decrease in glutathione and increase in homocysteine. Clinical trials in the last two decades have demonstrated that the use of specific nutrients can correct some of these metabolic derangements, improving symptom control and providing further benefits such as improved sensorium, blood flow and nerve regeneration. We will discuss the evidence on lipoic acid, acetyi-L-carnitine, benfotiamine and the combination of active B vitamins L-methylfolate, methylcobalamin and piridoxal-6-phosphate. In addition, we discuss the role of metforrnin, an important drug in the management of diabetes, and the presence of specific polymorphic genes, in the risk

  13. Presumptive binge eating disorder in type 2 diabetes mellitus patients and its effect in metabolic control

    Directory of Open Access Journals (Sweden)

    Sandra Soares Melo

    2009-09-01

    Full Text Available Objective: This study sought to determine the presence of diagnosis suggestive of binge eating disorder in individuals with type 2 diabetes mellitus, and to evaluate the influence of such disorder on the metabolic control. Methods: sixty-three patients with type 2 diabetes mellitus and registered  at the Diabetes and Hypertension Program of a Health Unit in the town of Balneário Camboriú, Santa Catarina, Brazil, were evaluated. The diagnosis of binge eating disorder was made by analysis of the Questionnaire on Eating and Weight Patterms – Revised. For the evaluation of metabolic control, 10 ml of blood was collected, and the serum glucose, glycated hemoglobin, tryglicerides, cholestrol and fractions were determined. Weight and height were determined for evaluation of national nutritional state, according to the body mass index. Rresults: Among the evaluated individuals, 29% presented a diagnosis suggestive of binge eating disorder, with higher prevalence among females. The individuals with diagnosis suggestive of binge eating disorder presented a higher average body mass index value than the group without diagnosis. The serum concentrations of glycated hemoglobin (p = 0.02 and triglicerides (p = 0.03 were statistically higher in the group with diagnosis suggestive of binge eating disorder. Cconclusions: Based on the results of this study, it is possible to conclude that the presence of binge eating disorder in individuals with type 2 diabetes mellitus favors an increase in body weight and has a negative influence on metabolic control, contributing to the early emergence of complications related to the disease.

  14. Comparative genomics of metabolic capacities of regulons controlled by cis-regulatory RNA motifs in bacteria.

    Science.gov (United States)

    Sun, Eric I; Leyn, Semen A; Kazanov, Marat D; Saier, Milton H; Novichkov, Pavel S; Rodionov, Dmitry A

    2013-09-02

    In silico comparative genomics approaches have been efficiently used for functional prediction and reconstruction of metabolic and regulatory networks. Riboswitches are metabolite-sensing structures often found in bacterial mRNA leaders controlling gene expression on transcriptional or translational levels.An increasing number of riboswitches and other cis-regulatory RNAs have been recently classified into numerous RNA families in the Rfam database. High conservation of these RNA motifs provides a unique advantage for their genomic identification and comparative analysis. A comparative genomics approach implemented in the RegPredict tool was used for reconstruction and functional annotation of regulons controlled by RNAs from 43 Rfam families in diverse taxonomic groups of Bacteria. The inferred regulons include ~5200 cis-regulatory RNAs and more than 12000 target genes in 255 microbial genomes. All predicted RNA-regulated genes were classified into specific and overall functional categories. Analysis of taxonomic distribution of these categories allowed us to establish major functional preferences for each analyzed cis-regulatory RNA motif family. Overall, most RNA motif regulons showed predictable functional content in accordance with their experimentally established effector ligands. Our results suggest that some RNA motifs (including thiamin pyrophosphate and cobalamin riboswitches that control the cofactor metabolism) are widespread and likely originated from the last common ancestor of all bacteria. However, many more analyzed RNA motifs are restricted to a narrow taxonomic group of bacteria and likely represent more recent evolutionary innovations. The reconstructed regulatory networks for major known RNA motifs substantially expand the existing knowledge of transcriptional regulation in bacteria. The inferred regulons can be used for genetic experiments, functional annotations of genes, metabolic reconstruction and evolutionary analysis. The obtained genome

  15. Contribution of family social support to the metabolic control of people with diabetes mellitus: A randomized controlled clinical trial.

    Science.gov (United States)

    Gomes, Lilian Cristiane; Coelho, Anna Claudia Martins; Gomides, Danielle Dos Santos; Foss-Freitas, Maria Cristina; Foss, Milton César; Pace, Ana Emilia

    2017-08-01

    This randomized controlled clinical trial aimed to evaluate the contribution of family social support to the clinical/metabolic control of people with type 2 diabetes mellitus. Diabetes mellitus is a chronic disease that requires continuous care in order for individuals to reach glycemic control, the primordial goal of treatment. Family social support is essential to the development of care skills and their maintenance. However, there are few studies that investigate the contribution of family social support to diabetes control. The study was developed between June 2011 and May 2013, and included 164 people who were randomized using simple randomization. The intervention group differed from the control group in that it included a family caregiver, who was recognized by the patient as a source of social support. The educational interventions received by people with diabetes mellitus were used as the basis of the education provided through telephone calls to patients' family members and caregivers, and their purpose was to encourage dialogue between the patients and their relatives about the topics related to diabetes. Regarding the clinical impact, the results showed that there was a greater reduction in blood pressure and glycated hemoglobin in the intervention group than in the control group, showing a positive effect on the control of the disease. Families should be incorporated into the care of people with diabetes mellitus and especially in health care programs, in particular those that can promote different forms of social support to strengthen the bond between family members. Copyright © 2017 Elsevier Inc. All rights reserved.

  16. Proton NMR metabolic profiling of CSF reveals distinct differentiation of meningitis from negative controls.

    Science.gov (United States)

    Chatterji, Tanushri; Singh, Suruchi; Sen, Manodeep; Singh, Ajai Kumar; Agarwal, Gaurav Raj; Singh, Deepak Kumar; Srivastava, Janmejai Kumar; Singh, Alka; Srivastava, Rajeshwar Nath; Roy, Raja

    2017-06-01

    Cerebrospinal fluid (CSF) is an essential bio-fluid of the central nervous system (CNS), playing a vital role in the protection of CNS and performing neuronal function regulation. The chemical composition of CSF varies during onset of meningitis, neurodegenerative disorders (positive controls) and in traumatic cases (negative controls). The study design was broadly categorized into meningitis cases, negative controls and positive controls. Further differentiation among the three groups was carried out using Principal Component Analysis (PCA) followed by supervised Partial Least Square Discriminant Analysis (PLS-DA). The statistical analysis of meningitis vs. negative controls using PLS-DA model resulted in R 2 of 0.97 and Q 2 of 0.85. There was elevation in the levels of ketone bodies, total free amino acids, glutamine, creatine, citrate and choline containing compounds (choline and GPC) in meningitis cases. Similarly, meningitis vs. positive controls resulted in R 2 of 0.80 and Q 2 of 0.60 and showed elevation in the levels of total free amino acids, glutamine, creatine/creatinine and citrate in the meningitis group. Four cases of HIV were identified by PLS-DA model as well as by clinical investigations. On the basis of metabolic profile it was found that negative control CSF samples are more appropriate for differentiation of meningitis than positive control CSF samples. Copyright © 2017 Elsevier B.V. All rights reserved.

  17. [Risk factors for metabolic syndrome in a case control study in Temuco, Chile].

    Science.gov (United States)

    Philco L, Patricia; Serón S, Pamela; Muñoz N, Sergio; Navia B, Pilar; Lanas Z, Fernando

    2012-03-01

    Metabolic syndrome is becoming an important public health problem in affluent societies. To identify factors associated to metabolic syndrome in a Southern Chilean city. Using a case control design, 200 participants, aged 35 to 70 years with at least three criteria for metabolic syndrome according to the National Cholesterol Education Program (NCEP_ATPIII) and 200 subjects with less than three criteria, were studied. Both groups were compared in terms of ethnic background, educational level, family history of diabetes and coronary artery disease, menopausal status, smoking, stress and depression, physical activity, changes in body mass index in the last five years and diet. Among subjects aged more than 54 years, among males and among overweight individuals, having a Mapuche origin was a risk factor with odds ratios (OR) of 7.2; 88 and 3.9 respectively. Among subjects aged more than 54 years, among women and among overweight individuals, a family history of diabetes was a risk factor with OR of 17.7; 3.2 and 3.9 respectively. Among subjects aged more than 54 years and among women a change in body mass index of more than three points was a risk factor with OR of 12.5 and 7.4, respectively. Depression also was a risk factor among subjects aged more than 54 years (OR 3.3). Regular consumption of wine was a protective factor among participants of more than 54 years, with an OR of 0.17. The risk factors for metabolic syndrome detected in this group of participants, were having a Mapuche origin, a family history of diabetes mellitus and depression. Wine consumption was associated with a lower risk.

  18. Metabolic control analysis of biochemical pathways based on a thermokinetic description of reaction rates

    DEFF Research Database (Denmark)

    Nielsen, Jens Bredal

    1997-01-01

    Metabolic control analysis is a powerful technique for the evaluation of flux control within biochemical pathways. Its foundation is the elasticity coefficients and the flux control coefficients (FCCs). On the basis of a thermokinetic description of reaction rates it is here shown...... that the elasticity coefficients can be calculated directly from the pool levels of metabolites at steady state. The only requirement is that one thermodynamic parameter be known, namely the reaction affinity at the intercept of the tangent in the inflection point of the curve of reaction rate against reaction...... of the thermokinetic description of reaction rates to include the influence of effecters. Here the reaction rate is written as a linear function of the logarithm of the metabolite concentrations. With this type of rate function it is shown that the approach of Delgado and Liao [Biochem. J. (1992) 282, 919-927] can...

  19. Metabolic control and bone health in adolescents with type 1 diabetes

    Directory of Open Access Journals (Sweden)

    Mohan Subburaman

    2011-10-01

    Full Text Available Abstract Background Adults with type 1 diabetes (T1D have decreased bone mineral density (BMD and increased fracture risk, yet the etiologies remain elusive. Early detection of derangements in bone biomarkers during adolescence could lead to timely recognition. In adolescents with T1D, we evaluated the relationships between metabolic control, BMD, and bone anabolic and turnover markers. Methods Cross-sectional study of 57 adolescent subjects with T1D who had HbA1c consistently ≥ 9% (Poor Control, PC n = 27 or Results There were no differences between HbA1c groups in BMD, components of the IGF system, or 25-hydroxyvitamin D status. The prevalence of 25-hydroxyvitamin D abnormalities was similar to that seen in the general adolescent population. Few patients met the recommended dietary allowance (RDA for vitamin D or calcium. Conclusions These data provide no evidence of association between degree of metabolic control and BMD in adolescents with T1D. Adolescents with T1D have a high prevalence of serum 25-hydroxyvitamin D abnormalities. Longitudinal studies are needed to evaluate the predictive value of vitamin D abnormalities on fracture risk.

  20. Effect of growth regulators on 'Brookfield' apple gas diffusion and metabolism under controlled atmosphere storage

    Directory of Open Access Journals (Sweden)

    Auri Brackmann

    2014-05-01

    Full Text Available The objective of this work was to evaluate the effect of growth regulators on gas diffusion and on metabolism of 'Brookfield' apple, and to determine their correlation with quality characteristics of fruit stored in controlled atmosphere. A completely randomized design was used with four replicates. After eight months of storage, the effects of water (control, aminoethoxyvinylglycine (AVG, AVG + ethephon, AVG + naphthaleneacetic acid (NAA, ethephon + NAA, sole NAA, 1-MCP, ethylene absorption by potassium permanganate (ABS, AVG + ABS, and of AVG + 1-MCP - applied at different rates and periods - were evaluated on: gas diffusion rate, ethylene production, respiratory rate, internal ethylene concentration, internal CO2 content, mealiness, and intercellular space. Fruit from the control and sole NAA treatments had the highest mealiness occurrence. Growth regulators significantly changed the gaseous diffusion through the pulp of 'Brookfield' apple, mainly in the treatment AVG + ABS, which kept the highest gas diffusion rate. NAA spraying in the field, with or without another growth regulator, increased ripening metabolism by rising ethylene production and respiration rate, and reduced gas diffusion during shelf life. AVG spraying cannot avoid the ethephon effect during the ripening process, and reduces both the internal space and mealiness incidence, but it is not able to induce ethylene production or to increase respiration rates.

  1. Mitochondrial metabolism and the control of vascular smooth muscle cell proliferation

    Directory of Open Access Journals (Sweden)

    Mario eChiong

    2014-12-01

    Full Text Available Differentiation and dedifferentiation of vascular smooth muscle cells (VSMCs are essential processes of vascular development. VSMCs have biosynthetic, proliferative and contractile roles in the vessel wall. Alterations in the differentiated state of the VSMCs play a critical role in the pathogenesis of a variety of cardiovascular diseases, including atherosclerosis, hypertension and vascular stenosis. This review provides an overview of the current state of knowledge of molecular mechanisms involved in the control of VSMC proliferation, with particular focus on mitochondrial metabolism. Mitochondrial activity can be controlled by regulating mitochondrial dynamics, i.e. mitochondrial fusion and fission, and by regulating mitochondrial calcium handling through the interaction with the endoplasmic reticulum (ER. Alterations in both VSMC proliferation and mitochondrial function can be triggered by dysregulation of mitofusin-2, a small GTPase associated with mitochondrial fusion and mitochondrial-ER interaction. Several lines of evidence highlight the relevance of mitochondrial metabolism in the control of VSMC proliferation, indicating a new area to be explored in the treatment of vascular diseases.

  2. The Good Work.

    Science.gov (United States)

    Csikszentmihalyi, Mihaly

    2003-01-01

    Examines the working lives of geneticists and journalists to place into perspective what lies behind personal ethics and success. Defines "good work" as productive activity that is valued socially and loved by people engaged in it. Asserts that certain cultural values, social controls, and personal standards are necessary to maintain good work and…

  3. Sense of coherence, self-esteem, and health locus of control in subjects with type 1 diabetes mellitus with/without satisfactory metabolic control.

    Science.gov (United States)

    Nuccitelli, C; Valentini, A; Caletti, M T; Caselli, C; Mazzella, N; Forlani, G; Marchesini, G

    2018-03-01

    Despite intensive training, a few individuals with Type 1 diabetes mellitus (T1DM) fail to reach the desired metabolic targets. To evaluate the association between disease-related emotional and cognitive aspects and metabolic control in subjects with T1DM. Health locus of control (HLOC), sense of coherence (SOC), and self-esteem were assessed in T1DM subjects using validated questionnaires. Sixty-seven consecutive subjects who did not attain the desired HbA1c target (mean HbA1c, 8.3% [67 mmol/mol]) were compared with 30 cases in satisfactory metabolic control (HbA1c levels satisfactory metabolic control tend to rely on significant others, trusting in the physicians' skills or on the efficiency of the health-care system. Strategies aimed at increasing self-efficacy and SOC, based on personal ability, are eagerly awaited to help patients improve diabetes care.

  4. Metabolic Control Analysis aimed at the ribose synthesis pathways of tumor cells: a new strategy for antitumor drug development

    NARCIS (Netherlands)

    Boren, Joan; Montoya, Antonio Ramos; de Atauri, Pedro; Comin-Anduix, Begoña; Cortes, Antonio; Centelles, Josep J.; Frederiks, Wilma M.; van Noorden, Cornelis J. F.; Cascante, Marta

    2002-01-01

    Metabolic control analysis predicts that effects on tumor growth are likely to be obtained with lower concentrations of drug, if an enzyme with a high control coefficient on tumor growth is being inhibited. Here we measure glucose-6-phosphate dehydrogenase (G6PDH) control coefficient on in vivo

  5. "Good mothering" or "good citizenship"?

    Science.gov (United States)

    Porter, Maree; Kerridge, Ian H; Jordens, Christopher F C

    2012-03-01

    Umbilical cord blood banking is one of many biomedical innovations that confront pregnant women with new choices about what they should do to secure their own and their child's best interests. Many mothers can now choose to donate their baby's umbilical cord blood (UCB) to a public cord blood bank or pay to store it in a private cord blood bank. Donation to a public bank is widely regarded as an altruistic act of civic responsibility. Paying to store UCB may be regarded as a "unique opportunity" to provide "insurance" for the child's future. This paper reports findings from a survey of Australian women that investigated the decision to either donate or store UCB. We conclude that mothers are faced with competing discourses that force them to choose between being a "good mother" and fulfilling their role as a "good citizen." We discuss this finding with reference to the concept of value pluralism.

  6. Evaluation of empowerment model on indicators of metabolic control in patients with type 2 diabetes, a randomized clinical trial study.

    Science.gov (United States)

    Ebrahimi, Hossein; Sadeghi, Mahdi; Amanpour, Farzaneh; Vahedi, Hamid

    2016-04-01

    Diabetes education is a major subject in achieving optimal glycemic control. Effective empowerment approach can be beneficial for improving patients' health. The aim of this study was to evaluate the effect of empowerment model on indicators of metabolic control in patients with type 2 diabetes. a randomized controlled trial of 103 patients with type 2 diabetes were randomly assigned to either the intervention (empowerment approach training) or the control group (conventional training) 2014. Empowerment approach training were performed for the experimental group for eight weeks. Data collection tool included demographic information form and indicators of metabolic control checklist. Analysis was performed by one-way analysis of variance, chi-square test, paired t-test, independent t-test and multiple linear regression. Before the intervention, two groups were homogeneous in terms of demographic variables, glycosylated hemoglobin (HbA1C), and other indicators of metabolic control. After the intervention, average HbA1C and other metabolic indicators except for LDL showed significant differences in the experimental group compared to the control group. study results indicated the positive effects of applying the empowerment model on the metabolic control indicators. Therefore, applying this model is recommended to nurses and the relevant authorities in order to improve clinical outcomes in diabetic patients. Copyright © 2015 Primary Care Diabetes Europe. Published by Elsevier Ltd. All rights reserved.

  7. The Relationship Between Maternal Awareness, Socioeconomic Situation of Families and Metabolic Control in Children With Type 1 Diabetes Miletus in an Iranian Population

    Directory of Open Access Journals (Sweden)

    Soheilipour

    2015-08-01

    Full Text Available Background Type 1 diabetes mellitus (T1DM is one of the most common chronic pediatric conditions, with potentially life-threatening sequels. However, good metabolic control can protect the patients against sequels. Objectives The aim of this study was to examine the relationship between awareness of the mothers about this disease on improving diabetic children metabolic control and also, to examine the relationship between socioeconomic situations of families and control of diabetes in this group of patients. Patients and Methods This is a cross-sectional descriptive analytic study on 80 diabetic children and their mothers, who were registered in the diabetes association of Iran, for outpatient control of disease. Diabetes knowledge was measured by Michigan diabetes knowledge test and glycemic control was assessed by glycosylated hemoglobin (HbA1c. To assess the socio-economic status of a diabetic child’s family, educational level, occupational and marital status of parents were asked and the socioeconomic status (SES was evaluated with Hollingshed four-factor index of SES. Results Mothers’ mean knowledge score was 17.72, children’s mean HbA1c was 7.77 and mean of SES was 27.89. There was no significant correlation between children’s HbA1c and mother’s SES. Also, there was an inverse linear relationship between mothers’ knowledge score and children’s HbA1c and there was a direct linear relationship between the mothers’ knowledge score and SES. Conclusions Finally, based on the results obtained in this study, it can be concluded that the awareness of mothers of T1DM children has a good impact on blood sugar control, whereas the SES of families has no direct effect on blood sugar control. Additionally, SES can indirectly impact on the consciousness of mothers and lead to the reduction of HbA1c.

  8. Thermodynamic and Probabilistic Metabolic Control Analysis of Riboflavin (Vitamin B₂) Biosynthesis in Bacteria.

    Science.gov (United States)

    Birkenmeier, Markus; Mack, Matthias; Röder, Thorsten

    2015-10-01

    In this study, we applied a coupled in silico thermodynamic and probabilistic metabolic control analysis methodology to investigate the control mechanisms of the commercially relevant riboflavin biosynthetic pathway in bacteria. Under the investigated steady-state conditions, we found that several enzyme reactions of the pathway operate far from thermodynamic equilibrium (transformed Gibbs energies of reaction below about -17 kJ mol(-1)). Using the obtained thermodynamic information and applying enzyme elasticity sampling, we calculated the distributions of the scaled concentration control coefficients (CCCs) and scaled flux control coefficients (FCCs). From the statistical analysis of the calculated distributions, we inferred that the control over the riboflavin producing flux is shared among several enzyme activities and mostly resides in the initial reactions of the pathway. More precisely, the guanosine triphosphate (GTP) cyclohydrolase II activity, and therefore the bifunctional RibA protein of Bacillus subtilis because it catalyzes this activity, appears to mainly control the riboflavin producing flux (mean FCCs = 0.45 and 0.55, respectively). The GTP cyclohydrolase II activity and RibA also exert a high positive control over the riboflavin concentration (mean CCCs = 2.43 and 2.91, respectively). This prediction is consistent with previous findings for microbial riboflavin overproducing strains.

  9. Measurement of Child Behavior via Classroom Observations in the Good Behavior Game Professional Development Models Randomized Control Trial

    Science.gov (United States)

    Kurki, Anja; Wang, Wei; Li, Yibing; Poduska, Jeanne

    2013-01-01

    The Good Behavior Game (GBG) is a classroom-based behavior management strategy aimed at reducing aggressive/disruptive behavior and socializing children into the role of student. GBG, delivered in first and second grades, has been shown to reduce rates of substance abuse and other deleterious outcomes into young adulthood (Brown, C.H. et al 2007,…

  10. Comparative genomic reconstruction of transcriptional networks controlling central metabolism in the Shewanella genus

    Directory of Open Access Journals (Sweden)

    Kovaleva Galina

    2011-06-01

    Full Text Available Abstract Background Genome-scale prediction of gene regulation and reconstruction of transcriptional regulatory networks in bacteria is one of the critical tasks of modern genomics. The Shewanella genus is comprised of metabolically versatile gamma-proteobacteria, whose lifestyles and natural environments are substantially different from Escherichia coli and other model bacterial species. The comparative genomics approaches and computational identification of regulatory sites are useful for the in silico reconstruction of transcriptional regulatory networks in bacteria. Results To explore conservation and variations in the Shewanella transcriptional networks we analyzed the repertoire of transcription factors and performed genomics-based reconstruction and comparative analysis of regulons in 16 Shewanella genomes. The inferred regulatory network includes 82 transcription factors and their DNA binding sites, 8 riboswitches and 6 translational attenuators. Forty five regulons were newly inferred from the genome context analysis, whereas others were propagated from previously characterized regulons in the Enterobacteria and Pseudomonas spp.. Multiple variations in regulatory strategies between the Shewanella spp. and E. coli include regulon contraction and expansion (as in the case of PdhR, HexR, FadR, numerous cases of recruiting non-orthologous regulators to control equivalent pathways (e.g. PsrA for fatty acid degradation and, conversely, orthologous regulators to control distinct pathways (e.g. TyrR, ArgR, Crp. Conclusions We tentatively defined the first reference collection of ~100 transcriptional regulons in 16 Shewanella genomes. The resulting regulatory network contains ~600 regulated genes per genome that are mostly involved in metabolism of carbohydrates, amino acids, fatty acids, vitamins, metals, and stress responses. Several reconstructed regulons including NagR for N-acetylglucosamine catabolism were experimentally validated in S

  11. Control of (pre-analytical aspects in immunoassay measurements of metabolic hormones in rodents

    Directory of Open Access Journals (Sweden)

    Maximilian Bielohuby

    2018-04-01

    Full Text Available The measurement of circulating hormones by immunoassay remains a cornerstone in preclinical endocrine research. For scientists conducting and interpreting immunoassay measurements of rodent samples, the paramount aim usually is to obtain reliable and meaningful measurement data in order to draw conclusions on biological processes. However, the biological variability between samples is not the only variable affecting the readout of an immunoassay measurement and a considerable amount of unwanted or unintended variability can be quickly introduced during the pre-analytical and analytical phase. This review aims to increase the awareness for the factors ‘pre-analytical’ and ‘analytical’ variability particularly in the context of immunoassay measurement of circulating metabolic hormones in rodent samples. In addition, guidance is provided how to gain control over these variables and how to avoid common pitfalls associated with sample collection, processing, storage and measurement. Furthermore, recommendations are given on how to perform a basic validation of novel single and multiplex immunoassays for the measurement of metabolic hormones in rodents. Finally, practical examples from immunoassay measurements of plasma insulin in mice address the factors ‘sampling site and inhalation anesthesia’ as frequent sources of introducing an unwanted variability during the pre-analytical phase. The knowledge about the influence of both types of variability on the immunoassay measurement of circulating hormones as well as strategies to control these variables are crucial, on the one hand, for planning and realization of metabolic rodent studies and, on the other hand, for the generation and interpretation of meaningful immunoassay data from rodent samples.

  12. Good self-control moderates the effect of mass media on adolescent tobacco and alcohol use: tests with studies of children and adolescents.

    Science.gov (United States)

    Wills, Thomas A; Gibbons, Frederick X; Sargent, James D; Gerrard, Meg; Lee, Hye-Ryeon; Dal Cin, Sonya

    2010-09-01

    To investigate whether self-control moderates the effect of media influences on tobacco and alcohol use among youth and if so how this effect occurs. In Study 1, a regional sample of 10-year olds (N = 290) was interviewed in households; attention to tobacco/alcohol advertising was assessed. In Study 2, a national sample of youth ages 10-14 years (N = 6,522) was surveyed by telephone; exposure to tobacco/alcohol use in movies was assessed. Good self-control was measured in both studies. Willingness to use substances and affiliation with peer substance users (Study 1); involvement in smoking or drinking (Study 2). In Study 1, the effect of tobacco/alcohol advertising on predisposition for substance use was lower among persons scoring higher on good self-control. In Study 2, the effect of movie smoking/alcohol exposure on adolescent tobacco/alcohol use was lower, concurrently and prospectively, among persons scoring higher on good self-control. Moderation occurred primarily through reducing the effect of movie exposure on positive smoking/alcohol expectancies and the effect of expectancies on adolescent use; some evidence for moderation of social processes was also noted. Covariates in the analyses included demographics, sensation seeking, and IQ. Good self-control reduces the effect of adverse media influences on adolescent tobacco and alcohol use. Findings on the processes underlying this effect may be useful for media literacy and primary prevention programs. (PsycINFO Database Record (c) 2010 APA, all rights reserved).

  13. Regulations of 10 January 1989 relating to the implementation of control of the export of strategic goods, services and technology, laid down by the ministry of foreign affairs

    International Nuclear Information System (INIS)

    1989-01-01

    These Regulations were made by the Ministry of Foreign Affairs in pursuance of Act No. 93 of 18 December 1987 on the control of the export of strategic goods, services and technology, in particular nuclear material, equipment, technology and services. The Regulations entered into force on 15 February 1989. That Ministry compiles lists of goods requiring an export licence or permission which also cover nuclear installations, material and equipment. The Regulations provide that the Ministry may require that an application for export of such goods, etc. be accompanied by a statement on the final use of the goods concerned (end-use statement) ascertaining that they will not be re-exported without the consent of the Norwegian authorities [fr

  14. Zinc Status Biomarkers and Cardiometabolic Risk Factors in Metabolic Syndrome: A Case Control Study

    Directory of Open Access Journals (Sweden)

    Erika P. S. Freitas

    2017-02-01

    Full Text Available Metabolic syndrome (MS involves pathophysiological alterations that might compromise zinc status. The aim of this study was to evaluate zinc status biomarkers and their associations with cardiometabolic factors in patients with MS. Our case control study included 88 patients with MS and 37 controls. We performed clinical and anthropometric assessments and obtained lipid, glycemic, and inflammatory profiles. We also evaluated zinc intake, plasma zinc, erythrocyte zinc, and 24-h urinary zinc excretion. The average zinc intake was significantly lower in the MS group (p < 0.001. Regression models indicated no significant differences in plasma zinc concentration (all p > 0.05 between the two groups. We found significantly higher erythrocyte zinc concentration in the MS group (p < 0.001 independent from co-variable adjustments. Twenty-four hour urinary zinc excretion was significantly higher in the MS group (p = 0.008, and adjustments for age and sex explained 21% of the difference (R2 = 0.21, p < 0.001. There were significant associations between zincuria and fasting blood glucose concentration (r = 0.479, waist circumference (r = 0.253, triglyceride concentration (r = 0.360, glycated hemoglobin concentration (r = 0.250, homeostatic model assessment—insulin resistance (r = 0.223, and high-sensitivity C-reactive protein concentration (r = 0.427 (all p < 0.05 in the MS group. Patients with MS had alterations in zinc metabolism mainly characterized by an increase in erythrocyte zinc and higher zincuria.

  15. Role of resting metabolic rate and energy expenditure in hunger and appetite control: a new formulation.

    Science.gov (United States)

    Blundell, John E; Caudwell, Phillipa; Gibbons, Catherine; Hopkins, Mark; Naslund, Erik; King, Neil; Finlayson, Graham

    2012-09-01

    A long-running issue in appetite research concerns the influence of energy expenditure on energy intake. More than 50 years ago, Otto G. Edholm proposed that "the differences between the intakes of food [of individuals] must originate in differences in the expenditure of energy". However, a relationship between energy expenditure and energy intake within any one day could not be found, although there was a correlation over 2 weeks. This issue was never resolved before interest in integrative biology was replaced by molecular biochemistry. Using a psychobiological approach, we have studied appetite control in an energy balance framework using a multi-level experimental system on a single cohort of overweight and obese human subjects. This has disclosed relationships between variables in the domains of body composition [fat-free mass (FFM), fat mass (FM)], metabolism, gastrointestinal hormones, hunger and energy intake. In this Commentary, we review our own and other data, and discuss a new formulation whereby appetite control and energy intake are regulated by energy expenditure. Specifically, we propose that FFM (the largest contributor to resting metabolic rate), but not body mass index or FM, is closely associated with self-determined meal size and daily energy intake. This formulation has implications for understanding weight regulation and the management of obesity.

  16. Role of resting metabolic rate and energy expenditure in hunger and appetite control: a new formulation

    Directory of Open Access Journals (Sweden)

    John E. Blundell

    2012-09-01

    Full Text Available A long-running issue in appetite research concerns the influence of energy expenditure on energy intake. More than 50 years ago, Otto G. Edholm proposed that “the differences between the intakes of food [of individuals] must originate in differences in the expenditure of energy”. However, a relationship between energy expenditure and energy intake within any one day could not be found, although there was a correlation over 2 weeks. This issue was never resolved before interest in integrative biology was replaced by molecular biochemistry. Using a psychobiological approach, we have studied appetite control in an energy balance framework using a multi-level experimental system on a single cohort of overweight and obese human subjects. This has disclosed relationships between variables in the domains of body composition [fat-free mass (FFM, fat mass (FM], metabolism, gastrointestinal hormones, hunger and energy intake. In this Commentary, we review our own and other data, and discuss a new formulation whereby appetite control and energy intake are regulated by energy expenditure. Specifically, we propose that FFM (the largest contributor to resting metabolic rate, but not body mass index or FM, is closely associated with self-determined meal size and daily energy intake. This formulation has implications for understanding weight regulation and the management of obesity.

  17. Act of 18 December 1987 relating to the control of the export of strategic goods, services and technology

    International Nuclear Information System (INIS)

    1987-01-01

    This Act controls the export of nuclear material and equipment and sensitive nuclear technology and services. In particular, it provides for strict controls and verification of certain exports. (NEA) [fr

  18. A Controlled Trial of CPAP Therapy on Metabolic Control in Individuals with Impaired Glucose Tolerance and Sleep Apnea

    Science.gov (United States)

    Weinstock, Tanya G.; Wang, Xuelei; Rueschman, Michael; Ismail-Beigi, Faramarz; Aylor, Joan; Babineau, Denise C.; Mehra, Reena; Redline, Susan

    2012-01-01

    Study Objectives: To address whether treatment of sleep apnea improves glucose tolerance. Design: Randomized, double-blind crossover study. Setting: Sleep clinic referrals. Patients: 50 subjects with moderate to severe sleep apnea (AHI > 15) and impaired glucose tolerance. Interventions: Subjects were randomized to 8 weeks of CPAP or sham CPAP, followed by the alternate therapy after a one-month washout. After each treatment, subjects underwent 2-hour OGTT, polysomnography, actigraphy, and measurements of indices of glucose control. Measurements and Results: The primary outcome was normalization of the mean 2-h OGTT; a secondary outcome was improvement in the Insulin Sensitivity Index (ISI (0,120). Subjects were 42% men, mean age of 54 (10), BMI of 39 (8), and AHI of 44 (27). Baseline fasting glucose was 104 (12), and mean 2-h OGTT was 110 (57) mg/dL. Seven subjects normalized their mean 2-h OGTT after CPAP but not after sham CPAP, while 5 subjects normalized after sham CPAP but not after CPAP. Overall, there was no improvement in ISI (0,120) between CPAP and sham CPAP (3.6%; 95% CI: [-2.2%, 9.7%]; P = 0.22). However, in those subjects with baseline AHI ≥ 30 (n = 25), there was a 13.3% (95% CI: [5.2%, 22.1%]; P CPAP compared to sham CPAP. Conclusions: This study did not show that IGT normalizes after CPAP in subjects with moderate sleep apnea and obesity. However, insulin sensitivity improved in those with AHI ≥ 30, suggesting beneficial metabolic effects of CPAP in severe sleep apnea. Clinical Trials Information: ClinicalTrials.gov Identifier: NCT01385995. Citation: Weinstock TG; Wang X; Rueschman M; Ismail-Beigi F; Aylor J; Babineau DC; Mehra R; Redline S. A controlled trial of CPAP therapy on metabolic control in individuals with impaired glucose tolerance and sleep apnea. SLEEP 2012;35(5):617-625. PMID:22547887

  19. 685. Order amending the Order concerning the definition of goods whose export requires a permit in accordance with the Security Control Act

    International Nuclear Information System (INIS)

    1990-01-01

    The list of goods which may not be exported without a permit, in accordance with the Act of 1972 on security control, was amended by this Order. The amendment includes numerous items or equipment involving radiation or radioactive materials. It came into effect on 1 December 1990. (NEA)

  20. Randomized Controlled Evaluation of the "Too Good for Drugs" Prevention Program: Impact on Adolescents at Different Risk Levels for Drug Use

    Science.gov (United States)

    Hall, Bruce W.; Bacon, Tina P.; Ferron, John M.

    2013-01-01

    Sixth graders participating in the "Too Good for Drugs" (TGFD) prevention program in comparison to 6th graders not participating show different results by student risk level. Sixth graders from 20 middle schools were randomly assigned to receive the intervention and those from 20 paired middle schools assigned to serve as controls (N =…

  1. Pakistan's national legislation entitled: 'Export Control on Goods, Technologies, Material and Equipment related to Nuclear and Biological Weapons and their Delivery Systems Act, 2004'

    International Nuclear Information System (INIS)

    2004-01-01

    The Director General has received a letter from the Permanent Mission of Pakistan, dated 4 November 2004, concerning Pakistan's national legislation entitled 'Export Control on Goods, Technologies, Material and Equipment related to Nuclear and Biological Weapons and their Delivery Systems Act, 2004'. As requested by the Permanent Mission of Pakistan, the letter and the Export Control Act of 2004, are reproduced herein for the information of the Member States

  2. Done good.

    Science.gov (United States)

    Caplan, A L

    2015-01-01

    How did bioethics manage to grow, flourish and ultimately do so well from a very unpromising birth in the 1970s? Many explanations have been advanced. Some ascribe the field's growth to a puzzling, voluntary abnegation of moral authority by medicine to non-physicians. Some think bioethics survived by selling out to the biomedical establishment-public and private. This transaction involved bestowing moral approbation on all manner of biomedicine's doings for a seat at a well-stocked funding table. Some see a sort of clever intellectual bamboozlement at work wherein bioethicists pitched a moral elixir of objective expertise that the morally needy but unsophisticated in medicine and the biological sciences were eager to swallow. While each of these reasons has its defenders, I think the main reason that bioethics did well was that it did good. By using the media to move into the public arena, the field engaged the public imagination, provoked dialogue and debate, and contributed to policy changes that benefitted patients and healthcare providers. Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://group.bmj.com/group/rights-licensing/permissions.

  3. Effects of short- and long-term Mediterranean-based dietary treatment on plasma LC-QTOF/MS metabolic profiling of subjects with metabolic syndrome features: The Metabolic Syndrome Reduction in Navarra (RESMENA) randomized controlled trial.

    Science.gov (United States)

    Bondia-Pons, Isabel; Martinez, José Alfredo; de la Iglesia, Rocio; Lopez-Legarrea, Patricia; Poutanen, Kaisa; Hanhineva, Kati; Zulet, Maria de los Ángeles

    2015-04-01

    Adherence to the Mediterranean diet has been associated with a reduced risk of metabolic syndrome (MetS). Metabolomics approach may contribute to identify beneficial associations of metabolic changes affected by Mediterranean diet-based interventions with inflammatory and oxidative-stress markers related to the etiology and development of the MetS. Liquid chromatography coupled to quadrupole-time of flight-MS metabolic profiling was applied to plasma from a 6-month randomized intervention with two sequential periods, a 2-month nutritional-learning intervention period, and a 4-month self-control period, with two energy-restricted diets; the RESMENA diet (based on the Mediterranean dietary pattern) and the Control diet (based on the American Heart Association guidelines), in 72 subjects with a high BMI and at least two features of MetS. The major contributing biomarkers of each sequential period were lipids, mainly phospholipids and lysophospholipids. Dependency network analysis showed a different pattern of associations between metabolic changes and clinical variables after 2 and 6 month of intervention, with a highly interconnected network during the nutritional-learning intervention period of the study. The 2-month RESMENA diet produced significant changes in the plasma metabolic profile of subjects with MetS features. However, at the end of the 6-month study, most of the associations between metabolic and clinical variables disappeared; suggesting that adherence to healthy dietary habits had declined during the self-control period. © 2015 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

  4. Reduced Metabolism in Brain 'Control Networks' Following Cocaine-Cues Exposure in Female Cocaine Abusers

    International Nuclear Information System (INIS)

    Volkow, N.D.; Tomasi, D.; Wang, G.-J.; Fowler, J.S.; Telang, F.; Goldstein, R.Z.; Alia-Klein, N.; Wong, C.T.

    2011-01-01

    Gender differences in vulnerability for cocaine addiction have been reported. Though the mechanisms are not understood, here we hypothesize that gender differences in reactivity to conditioned-cues, which contributes to relapse, are involved. To test this we compared brain metabolism (using PET and 18 FDG) between female (n = 10) and male (n = 16) active cocaine abusers when they watched a neutral video (nature scenes) versus a cocaine-cues video. Self-reports of craving increased with the cocaine-cue video but responses did not differ between genders. In contrast, changes in whole brain metabolism with cocaine-cues differed by gender (p<0.05); females significantly decreased metabolism (-8.6% ± 10) whereas males tended to increase it (+5.5% ± 18). SPM analysis (Cocaine-cues vs Neutral) in females revealed decreases in frontal, cingulate and parietal cortices, thalamus and midbrain (p<0.001) whereas males showed increases in right inferior frontal gyrus (BA 44/45) (only at p<0.005). The gender-cue interaction showed greater decrements with Cocaine-cues in females than males (p<0.001) in frontal (BA 8, 9, 10), anterior cingulate (BA 24, 32), posterior cingulate (BA 23, 31), inferior parietal (BA 40) and thalamus (dorsomedial nucleus). Females showed greater brain reactivity to cocaine-cues than males but no differences in craving, suggesting that there may be gender differences in response to cues that are not linked with craving but could affect subsequent drug use. Specifically deactivation of brain regions from 'control networks' (prefrontal, cingulate, inferior parietal, thalamus) in females could increase their vulnerability to relapse since it would interfere with executive function (cognitive inhibition). This highlights the importance of gender tailored interventions for cocaine addiction.

  5. Reduced metabolism in brain "control networks" following cocaine-cues exposure in female cocaine abusers.

    Directory of Open Access Journals (Sweden)

    Nora D Volkow

    2011-02-01

    Full Text Available Gender differences in vulnerability for cocaine addiction have been reported. Though the mechanisms are not understood, here we hypothesize that gender differences in reactivity to conditioned-cues, which contributes to relapse, are involved.To test this we compared brain metabolism (using PET and ¹⁸FDG between female (n = 10 and male (n = 16 active cocaine abusers when they watched a neutral video (nature scenes versus a cocaine-cues video.Self-reports of craving increased with the cocaine-cue video but responses did not differ between genders. In contrast, changes in whole brain metabolism with cocaine-cues differed by gender (p<0.05; females significantly decreased metabolism (-8.6%±10 whereas males tended to increase it (+5.5%±18. SPM analysis (Cocaine-cues vs Neutral in females revealed decreases in frontal, cingulate and parietal cortices, thalamus and midbrain (p<0.001 whereas males showed increases in right inferior frontal gyrus (BA 44/45 (only at p<0.005. The gender-cue interaction showed greater decrements with Cocaine-cues in females than males (p<0.001 in frontal (BA 8, 9, 10, anterior cingulate (BA 24, 32, posterior cingulate (BA 23, 31, inferior parietal (BA 40 and thalamus (dorsomedial nucleus.Females showed greater brain reactivity to cocaine-cues than males but no differences in craving, suggesting that there may be gender differences in response to cues that are not linked with craving but could affect subsequent drug use. Specifically deactivation of brain regions from "control networks" (prefrontal, cingulate, inferior parietal, thalamus in females could increase their vulnerability to relapse since it would interfere with executive function (cognitive inhibition. This highlights the importance of gender tailored interventions for cocaine addiction.

  6. Female fibromyalgia patients: lower resting metabolic rates than matched healthy controls.

    Science.gov (United States)

    Lowe, John C; Yellin, Jackie; Honeyman-Lowe, Gina

    2006-07-01

    Many features of fibromyalgia and hypothyroidism are virtually the same, and thyroid hormone treatment trials have reduced or eliminated fibromyalgia symptoms. These findings led the authors to test the hypothesis that fibromyalgia patients are hypometabolic compared to matched controls. Resting metabolic rate (RMR) was measured by indirect calorimetry and body composition by bioelectrical impedance for 15 fibromyalgia patients and 15 healthy matched controls. Measured resting metabolic rate (mRMR) was compared to percentages of predicted RMR (pRMR) by fat-free weight (FFW) (Sterling-Passmore: SP) and by sex, age, height, and weight (Harris-Benedict: HB). Patients had a lower mRMR (4,306.31+/-1077.66 kJ vs 5,411.59+/-695.95 kJ, p=0.0028) and lower percentages of pRMRs (SP: -28.42+/-15.82% vs -6.83+/-12.55%, pBMI) best accounted for variability in controls' RMRs, age and fat weight (FW) did for patients. In the patient group, TSH level accounted for 28% of the variance in pain distribution, and free T3 (FT3) accounted for 30% of the variance in pressure-pain threshold. Patients had lower mRMR and percentages of pRMRs. The lower RMRs were not due to calorie restriction or low FFW. Patients' normal FFW argues against low physical activity as the mechanism. TSH, FT4, and FT3 levels did not correlate with RMRs in either group. This does not rule out inadequate thyroid hormone regulation because studies show these laboratory values do not reliably predict RMR.

  7. Multidisciplinary Treatment of the Metabolic Syndrome Lowers Blood Pressure Variability Independent of Blood Pressure Control.

    Science.gov (United States)

    Marcus, Yonit; Segev, Elad; Shefer, Gabi; Sack, Jessica; Tal, Brurya; Yaron, Marianna; Carmeli, Eli; Shefer, Lili; Margaliot, Miri; Limor, Rona; Gilad, Suzan; Sofer, Yael; Stern, Naftali

    2016-01-01

    Blood pressure (BP) variability (BPV) contributes to target organ damage independent of BP. The authors examined the effect of a 1-year multidisciplinary intervention on BPV in patients with the metabolic syndrome (MetS) as defined by criteria from the Third Report of the Adult Treatment Panel. Forty-four nondiabetic patients underwent clinical and biochemical profiling, 24-hour ambulatory BP monitoring (ABPM), body composition, carotid intima-media thickness, and carotid-femoral pulse wave velocity (PWV). The intervention targeted all MetS components. BPV was assessed by the standard deviation of daytime systolic BP derived from ABPM. Patients with low and high BPV (lower or higher than the median daytime standard deviation of 11.6 mm Hg) did not differ in regards to systolic and diastolic BP, age, fasting glucose, glycated hemoglobin, and body mass index, but the high-variability group had higher values of low-density lipoprotein and leg fat. The 1-year intervention resulted in weight reduction but not BP-lowering. BPV declined in the high-variability group in association with lowering of PWV, C-reactive protein, glycated hemoglobin, alanine aminotransferase, asymmetric dimethylarginine, and increased high-density lipoprotein cholesterol. A multidisciplinary intervention independent of BP-lowering normalized BPV, lowered PWV, and enhanced metabolic control. © 2015 Wiley Periodicals, Inc.

  8. The effects of nocturnal compared with conventional hemodialysis on mineral metabolism: A randomized-controlled trial.

    Science.gov (United States)

    Walsh, Michael; Manns, Braden J; Klarenbach, Scott; Tonelli, Marcello; Hemmelgarn, Brenda; Culleton, Bruce

    2010-04-01

    Hyperphosphatemia is common among patients receiving dialysis and is associated with increased mortality. Nocturnal hemodialysis (NHD) is a long, slow dialytic modality that may improve hyperphosphatemia and disorders of mineral metabolism. We performed a randomized-controlled trial of NHD compared with conventional hemodialysis (CvHD); in this paper, we report detailed results of mineral metabolism outcomes. Prevalent patients were randomized to receive NHD 5 to 6 nights per week for 6to 10 hours per night or to continue CvHD thrice weekly for 6 months. Oral phosphate binders and vitamin D analogs were adjusted to maintain phosphate, calcium and parathyroid hormone (PTH) levels within recommended targets. Compared with CvHD patients, patients in the NHD group had a significant decrease in serum phosphate over the course of the study (0.49 mmol/L, 95% confidence interval 0.24-0.74; P=0.002) despite a significant reduction in the use of phosphate binders. Sixty-one percent of patients in the NHD group compared with 20% in the CvHD group had a decline in intact PTH (P=0.003). Nocturnal hemodialysis lowers serum phosphate, calcium-phosphate product and requirement for phosphate binders. The effects of NHD on PTH are variable. The impact of these changes on long-term cardiovascular and bone-related outcomes requires further investigation.

  9. On the use of metabolic control analysis in the optimization of cyanobacterial biosolar cell factories.

    Science.gov (United States)

    Angermayr, S Andreas; Hellingwerf, Klaas J

    2013-09-26

    Oxygenic photosynthesis will have a key role in a sustainable future. It is therefore significant that this process can be engineered in organisms such as cyanobacteria to construct cell factories that catalyze the (sun)light-driven conversion of CO2 and water into products like ethanol, butanol, or other biofuels or lactic acid, a bioplastic precursor, and oxygen as a byproduct. It is of key importance to optimize such cell factories to maximal efficiency. This holds for their light-harvesting capabilities under, for example, circadian illumination in large-scale photobioreactors. However, this also holds for the "dark" reactions of photosynthesis, that is, the conversion of CO2, NADPH, and ATP into a product. Here, we present an analysis, based on metabolic control theory, to estimate the optimal capacity for product formation with which such cyanobacterial cell factories have to be equipped. Engineered l-lactic acid producing Synechocystis sp. PCC6803 strains are used to identify the relation between production rate and enzymatic capacity. The analysis shows that the engineered cell factories for l-lactic acid are fully limited by the metabolic capacity of the product-forming pathway. We attribute this to the fact that currently available promoter systems in cyanobacteria lack the genetic capacity to a provide sufficient expression in single-gene doses.

  10. PHB Associates with the HIRA Complex to Control an Epigenetic-Metabolic Circuit in Human ESCs.

    Science.gov (United States)

    Zhu, Zhexin; Li, Chunliang; Zeng, Yanwu; Ding, Jianyi; Qu, Zepeng; Gu, Junjie; Ge, Laixiang; Tang, Fan; Huang, Xin; Zhou, Chenlin; Wang, Ping; Zheng, Deyou; Jin, Ying

    2017-02-02

    The chromatin landscape and cellular metabolism both contribute to cell fate determination, but their interplay remains poorly understood. Using genome-wide siRNA screening, we have identified prohibitin (PHB) as an essential factor in self-renewal of human embryonic stem cells (hESCs). Mechanistically, PHB forms protein complexes with HIRA, a histone H3.3 chaperone, and stabilizes the protein levels of HIRA complex components. Like PHB, HIRA is required for hESC self-renewal. PHB and HIRA act together to control global deposition of histone H3.3 and gene expression in hESCs. Of particular note, PHB and HIRA regulate the chromatin architecture at the promoters of isocitrate dehydrogenase genes to promote transcription and, thus, production of α-ketoglutarate, a key metabolite in the regulation of ESC fate. Our study shows that PHB has an unexpected nuclear role in hESCs that is required for self-renewal and that it acts with HIRA in chromatin organization to link epigenetic organization to a metabolic circuit. Copyright © 2017 Elsevier Inc. All rights reserved.

  11. The Deubiquitylase MATH-33 Controls DAF-16 Stability and Function in Metabolism and Longevity.

    Science.gov (United States)

    Heimbucher, Thomas; Liu, Zheng; Bossard, Carine; McCloskey, Richard; Carrano, Andrea C; Riedel, Christian G; Tanasa, Bogdan; Klammt, Christian; Fonslow, Bryan R; Riera, Celine E; Lillemeier, Bjorn F; Kemphues, Kenneth; Yates, John R; O'Shea, Clodagh; Hunter, Tony; Dillin, Andrew

    2015-07-07

    FOXO family transcription factors are downstream effectors of Insulin/IGF-1 signaling (IIS) and major determinants of aging in organisms ranging from worms to man. The molecular mechanisms that actively promote DAF16/FOXO stability and function are unknown. Here we identify the deubiquitylating enzyme MATH-33 as an essential DAF-16 regulator in IIS, which stabilizes active DAF-16 protein levels and, as a consequence, influences DAF-16 functions, such as metabolism, stress response, and longevity in C. elegans. MATH-33 associates with DAF-16 in cellulo and in vitro. MATH-33 functions as a deubiquitylase by actively removing ubiquitin moieties from DAF-16, thus counteracting the action of the RLE-1 E3-ubiquitin ligase. Our findings support a model in which MATH-33 promotes DAF-16 stability in response to decreased IIS by directly modulating its ubiquitylation state, suggesting that regulated oscillations in the stability of DAF-16 protein play an integral role in controlling processes such as metabolism and longevity. Copyright © 2015 Elsevier Inc. All rights reserved.

  12. Rapid selection of a pyrethroid metabolic enzyme CYP9K1 by operational malaria control activities.

    Science.gov (United States)

    Vontas, John; Grigoraki, Linda; Morgan, John; Tsakireli, Dimitra; Fuseini, Godwin; Segura, Luis; Niemczura de Carvalho, Julie; Nguema, Raul; Weetman, David; Slotman, Michel A; Hemingway, Janet

    2018-05-01

    Since 2004, indoor residual spraying (IRS) and long-lasting insecticide-impregnated bednets (LLINs) have reduced the malaria parasite prevalence in children on Bioko Island, Equatorial Guinea, from 45% to 12%. After target site-based (knockdown resistance; kdr ) pyrethroid resistance was detected in 2004 in Anopheles coluzzii (formerly known as the M form of the Anopheles gambiae complex), the carbamate bendiocarb was introduced. Subsequent analysis showed that kdr alone was not operationally significant, so pyrethroid-based IRS was successfully reintroduced in 2012. In 2007 and 2014-2015, mass distribution of new pyrethroid LLINs was undertaken to increase the net coverage levels. The combined selection pressure of IRS and LLINs resulted in an increase in the frequency of pyrethroid resistance in 2015. In addition to a significant increase in kd r frequency, an additional metabolic pyrethroid resistance mechanism had been selected. Increased metabolism of the pyrethroid deltamethrin was linked with up-regulation of the cytochrome P450 CYP9K1. The increase in resistance prompted a reversion to bendiocarb IRS in 2016 to avoid a resurgence of malaria, in line with the national Malaria Control Program plan. Copyright © 2018 the Author(s). Published by PNAS.

  13. Neural control of blood flow during exercise in human metabolic syndrome.

    Science.gov (United States)

    Limberg, Jacqueline K; Morgan, Barbara J; Sebranek, Joshua J; Proctor, Lester T; Eldridge, Marlowe W; Schrage, William G

    2014-09-01

    α-Adrenergic-mediated vasoconstriction is greater during simulated exercise in animal models of metabolic syndrome (MetSyn) when compared with control animals. In an attempt to translate such findings to humans, we hypothesized that adults with MetSyn (n = 14, 35 ± 3 years old) would exhibit greater α-adrenergic responsiveness during exercise when compared with age-matched healthy control subjects (n = 16, 31 ± 3 years old). We measured muscle sympathetic nerve activity (MSNA; microneurography) and forearm blood flow (Doppler ultrasound) during dynamic forearm exercise (15% of maximal voluntary contraction). α-Adrenergic agonists (phenylephrine and clonidine) and an antagonist (phentolamine) were infused intra-arterially to assess α-adrenergic receptor responsiveness and restraint, respectively. Resting MSNA was ∼35% higher in adults with MetSyn (P exercise. Clonidine-mediated vasoconstriction was greater in adults with MetSyn (P  0.05). Interestingly, exercise-mediated vasodilatation was greater in MetSyn (P exercise blood flow during low-intensity hand-grip exercise when compared with age-matched healthy control subjects. These results suggest that adults with MetSyn exhibit compensatory vascular control mechanisms capable of preserving blood flow responses to exercise in the face of augmented sympathetic adrenergic activity. © 2014 The Authors. Experimental Physiology © 2014 The Physiological Society.

  14. Pregnancy and lactation alter biomarkers of biotin metabolism in women consuming a controlled diet.

    Science.gov (United States)

    Perry, Cydne A; West, Allyson A; Gayle, Antoinette; Lucas, Lauren K; Yan, Jian; Jiang, Xinyin; Malysheva, Olga; Caudill, Marie A

    2014-12-01

    Biotin functions as a cofactor for several carboxylase enzymes with key roles in metabolism. At present, the dietary requirement for biotin is unknown and intake recommendations are provided as Adequate Intakes (AIs). The biotin AI for adults and pregnant women is 30 μg/d, whereas 35 μg/d is recommended for lactating women. However, pregnant and lactating women may require more biotin to meet the demands of these reproductive states. The current study sought to quantify the impact of reproductive state on biotin status response to a known dietary intake of biotin. To achieve this aim, we measured a panel of biotin biomarkers among pregnant (gestational week 27 at study entry; n = 26), lactating (postnatal week 5 at study entry; n = 28), and control (n = 21) women who participated in a 10- to 12-wk feeding study providing 57 μg of dietary biotin/d as part of a mixed diet. Over the course of the study, pregnant women excreted 69% more (vs. control; P biotin-dependent methylcrotonyl-coenzyme A carboxylase is impaired. Interestingly, urinary excretion of 3-hydroxyisovaleryl-carnitine (3-HIA-carnitine), a downstream metabolite of 3-HIA, was 27% lower (P = 0.05) among pregnant (vs. control) women, a finding that may arise from carnitine inadequacy during gestation. No differences (P > 0.05) were detected in plasma biotin, urinary biotin, or urinary bisnorbiotin between pregnant and control women. Lactating women excreted 76% more (vs. control; P = 0.001) of the biotin catabolite bisnorbiotin, indicating that lactation accelerates biotin turnover and loss. Notably, with respect to control women, lactating women excreted 23% less (P = 0.04) urinary 3-HIA and 26% less (P = 0.05) urinary 3-HIA-carnitine, suggesting that lactation reduces leucine catabolism and that these metabolites may not be useful indicators of biotin status during lactation. Overall, these data demonstrate significant alterations in markers of biotin metabolism during pregnancy and lactation and

  15. Pregnancy and Lactation Alter Biomarkers of Biotin Metabolism in Women Consuming a Controlled Diet123

    Science.gov (United States)

    Perry, Cydne A; West, Allyson A; Gayle, Antoinette; Lucas, Lauren K; Yan, Jian; Jiang, Xinyin; Malysheva, Olga; Caudill, Marie A

    2014-01-01

    Background: Biotin functions as a cofactor for several carboxylase enzymes with key roles in metabolism. At present, the dietary requirement for biotin is unknown and intake recommendations are provided as Adequate Intakes (AIs). The biotin AI for adults and pregnant women is 30 μg/d, whereas 35 μg/d is recommended for lactating women. However, pregnant and lactating women may require more biotin to meet the demands of these reproductive states. Objective: The current study sought to quantify the impact of reproductive state on biotin status response to a known dietary intake of biotin. Methods: To achieve this aim, we measured a panel of biotin biomarkers among pregnant (gestational week 27 at study entry; n = 26), lactating (postnatal week 5 at study entry; n = 28), and control (n = 21) women who participated in a 10- to 12-wk feeding study providing 57 μg of dietary biotin/d as part of a mixed diet. Results: Over the course of the study, pregnant women excreted 69% more (vs. control; P biotin-dependent methylcrotonyl–coenzyme A carboxylase is impaired. Interestingly, urinary excretion of 3-hydroxyisovaleryl-carnitine (3-HIA-carnitine), a downstream metabolite of 3-HIA, was 27% lower (P = 0.05) among pregnant (vs. control) women, a finding that may arise from carnitine inadequacy during gestation. No differences (P > 0.05) were detected in plasma biotin, urinary biotin, or urinary bisnorbiotin between pregnant and control women. Lactating women excreted 76% more (vs. control; P = 0.001) of the biotin catabolite bisnorbiotin, indicating that lactation accelerates biotin turnover and loss. Notably, with respect to control women, lactating women excreted 23% less (P = 0.04) urinary 3-HIA and 26% less (P = 0.05) urinary 3-HIA-carnitine, suggesting that lactation reduces leucine catabolism and that these metabolites may not be useful indicators of biotin status during lactation. Conclusions: Overall, these data demonstrate significant alterations in markers of

  16. TPL-2 Regulates Macrophage Lipid Metabolism and M2 Differentiation to Control TH2-Mediated Immunopathology

    Science.gov (United States)

    Entwistle, Lewis J.; Khoury, Hania; Papoutsopoulou, Stamatia; Mahmood, Radma; Mansour, Nuha R.; Ching-Cheng Huang, Stanley; Pearce, Edward J.; Pedro S. de Carvalho, Luiz; Ley, Steven C.

    2016-01-01

    Persistent TH2 cytokine responses following chronic helminth infections can often lead to the development of tissue pathology and fibrotic scarring. Despite a good understanding of the cellular mechanisms involved in fibrogenesis, there are very few therapeutic options available, highlighting a significant medical need and gap in our understanding of the molecular mechanisms of TH2-mediated immunopathology. In this study, we found that the Map3 kinase, TPL-2 (Map3k8; Cot) regulated TH2-mediated intestinal, hepatic and pulmonary immunopathology following Schistosoma mansoni infection or S. mansoni egg injection. Elevated inflammation, TH2 cell responses and exacerbated fibrosis in Map3k8 –/–mice was observed in mice with myeloid cell-specific (LysM) deletion of Map3k8, but not CD4 cell-specific deletion of Map3k8, indicating that TPL-2 regulated myeloid cell function to limit TH2-mediated immunopathology. Transcriptional and metabolic assays of Map3k8 –/–M2 macrophages identified that TPL-2 was required for lipolysis, M2 macrophage activation and the expression of a variety of genes involved in immuno-regulatory and pro-fibrotic pathways. Taken together this study identified that TPL-2 regulated TH2-mediated inflammation by supporting lipolysis and M2 macrophage activation, preventing TH2 cell expansion and downstream immunopathology and fibrosis. PMID:27487182

  17. Genetic algorithm to optimize two-echelon inventory control system for perishable goods in terms of active packaging

    Directory of Open Access Journals (Sweden)

    Babak Yousefi Yegane

    2012-01-01

    Full Text Available This paper considers an inventory control policy for a two-echelon inventory control system with one supplier-one buyer. We consider the case of deteriorating items which lead to shortage in supply chain. Therefore, it is necessary to decrease the deterioration rate by adding some specification to the packaging of these items that is known as active packaging. Although this packaging can reduce the deteriorating rate of products, but may be increases the cost of both supplier and buyer. Because of the complexity of the mathematical model, a genetic algorithm has been developed to determine the best policy of this inventory control system.

  18. Target setting in intensive insulin management is associated with metabolic control

    DEFF Research Database (Denmark)

    Swift, P G F; Skinner, T C; de Beaufort, C E

    2010-01-01

    Objective: To evaluate glycaemic targets set by diabetes teams, their perception by adolescents and parents, and their influence on metabolic control. Methods: Clinical data and questionnaires were completed by adolescents, parents/carers and diabetes teams in 21 international centres. HbA1c...... was measured centrally. Results: A total of 2062 adolescents completed questionnaires (age 14.4 +/- 2.3 yr; diabetes duration 6.1 +/- 3.5 yr). Mean HbA 1c = 8.2 +/- 1.4% with significant differences between centres (F = 12.3; p ... (r = 0.20) and adolescent (r = 0.21) reports of their perceived ideal HbA1c and their actual HbA1c result (p adolescents' (r = 0.4) reports of the HbA1c they would be happy with and their actual HbA1c result. There were significant...

  19. Prevalence of chronic complications, metabolic control and nutritional intake in type 1 diabetes

    DEFF Research Database (Denmark)

    Toeller, M; Buyken, A E; Heitkamp, G

    1999-01-01

    and proliferative retinopathy were more common. Persons from the eastern European and the German centres consumed undesirably high amounts of cholesterol, total and saturated fat. Overall, improvements in the prevention, detection and management of diabetes complications in persons with type 1 diabetes......) and chronic diabetes complications (retinopathy, nephropathy, neuropathy, cardiovascular disease) were all considerably more frequent in the eastern European centres. HbA1c was lower in the German centres than in the total EURODIAB cohort or in the north-western European centres, but severe hypoglycaemia......This study compares the prevalence of chronic complications, the quality of metabolic control and the nutritional intake in people with type 1 diabetes in different European regions. The EURODIAB Complications Study included a sample of 3250 European patients with type 1 diabetes stratified...

  20. Fractional exhaled nitric oxide has a good correlation with asthma control and lung function in latino children with asthma.

    Science.gov (United States)

    Soto-Ramos, Mario; Castro-Rodríguez, Jose A; Hinojos-Gallardo, Luis Carlos; Hernández-Saldaña, Raul; Cisneros-Castolo, Martin; Carrillo-Rodríguez, Victor

    2013-08-01

    Although the measurement of fractional exhaled nitric oxide (FE(NO)) has been recommended for observational studies and clinical trials of asthma, FE(NO) has not been examined in studies of childhood asthma in Latin America, To examine the relationship between FE(NO) and indicators of disease control or severity [asthma control test/childhood asthma control test (ACT/C-ACT), lung function, and exercise challenge test (ECT)] in Mexican children with persistent asthma, Children (6-18 years of age) with persistent asthma were consecutively recruited in a tertiary asthma clinic and divided into two groups, e.g. FE(NO) children, Children with FE(NO)children with FE(NO) ≥20 ppb, those with FE(NO) children with persistent asthma, low levels of FE(NO) ( asthma control, and higher lung function.

  1. Microbiological changes after periodontal therapy in diabetic patients with inadequate metabolic control

    Directory of Open Access Journals (Sweden)

    Carina Maciel Silva-Boghossian

    2014-05-01

    Full Text Available The present study investigated the effect of non-surgical periodontal treatment (SRP on the composition of the subgingival microbiota of chronic periodontitis (CP in individuals with type 2 diabetes (DM2 with inadequate metabolic control and in systemically healthy (SH individuals. Forty individuals (20 DM2 and 20 SH with CP underwent full-mouth periodontal examination. Subgingival plaque was sampled from 4 deep sites of each individual and tested for mean prevalence and counts of 45 bacterial taxa by the checkerboard method. Clinical and microbiological assessments were performed before and 3 months after SRP. At baseline, those in the DM2 group presented a significantly higher percentage of sites with visible plaque and bleeding on probing compared with those in the SH group (p < 0.01. Those in the DM2 group presented significantly higher levels of C. rectus and P. gingivalis, and lower prevalence of P. micra and S. anginosus, compared with those in the SH group (p ≤ 0.001. At the 3-month visit, both groups showed a significant improvement in all clinical parameters (p < 0.01. Those in the DM2 group showed significantly higher prevalence and/or levels of A. gerencseriae, A. naeslundii I, A. oris, A. odontolyticus, C. sputigena, F. periodonticum, and G. morbillorum compared with those in the SH group (p ≤ 0.001. However, those in the DM2 group showed a significant reduction in the levels of P. intermedia, P. gingivalis, T. forsythia, and T. denticola (p ≤ 0.001 over time. Those in the SRP group showed improved periodontal status and reduced levels of putative periodontal pathogens at 3 months’ evaluation compared with those in the DM2 group with inadequate metabolic control.

  2. [Impact of metabolic syndrome in the control of blood pressure and dyslipemia].

    Science.gov (United States)

    Rodilla, Enrique; García, Luis; Merino, Consolación; Costa, José A; González, Carmen; Pascual, José M

    2004-11-06

    The objective of the study was to assess the influence of metabolic syndrome (MS) in the control of blood pressure (BP) and dyslipemia. A cross sectional study was performed with 1,320 (634 M and 686 F), 40.1 (13.3) years-old, BMI 29.8 (4.7) hypertensive non-diabetic patients. MS was diagnosed according to NCEP-ATP-III guidelines. Blood pressure control goal was BP 20% at 10 years). Goals of C-LDL levels were those of NCEP-ATP-III. 461 (35%) patients had MS and the remaining 859 became controls. Patients with MS had higher initial levels of hypertension and were receiving more antihypertensive drugs: 2.1 [1.3] vs. 1.7 [1.3]; p < 0.001), yet the average systolic and diastolic BP achieved and the degree of control was similar in both groups 53% vs. 52%; (p = ns). Patients with MS had higher CR at ten years than controls (10.7 [8.3] vs. 7.9 [6.8], p < 0.001) but achieved the C-LDL goals at fewer proportions than controls (57% vs. 74%; p < 0.001). In a regression analysis, patients with MS had 26% less probabilities of achieving both goals (p < 0.001). Hypertensive patients with MS have higher CR, and need more antihypertensive drugs to achieve the same BP goals. Yet it is more difficult for them to achieve LDL cholesterol goals. Patients with MS remain a target for cardiovascular prevention.

  3. Good intentions gone awry? Effects of weight-related social control on health and well-being.

    Science.gov (United States)

    Brunson, Julie A; Overup, Camilla S; Nguyen, Mai-Ly; Novak, Sarah A; Smith, C Veronica

    2014-01-01

    A negative body image has been associated with a variety of negative health and well-being outcomes. Social pressures from others, in the form of weight-related social control, may serve to exacerbate this effect, especially for college-aged women. Undergraduate students (N=399) completed a variety of questionnaires assessing weight-related social control, well-being, and diet and exercise behaviors. The results suggest that weight is associated with a variety of negative health and well-being outcomes and particularly for women, weight-related social control is also associated with these negative effects. In addition, men of higher body mass indexes (BMIs) or higher self-perceived weight did not experience negative health and well-being outcomes to the same degree that overweight women did. Parents in particular seem to instigate weight-related social control to change students' diet and exercise behaviors. These results help clarify the effects of weight-related social control in a college population, where weight may be especially important. Copyright © 2013 Elsevier Ltd. All rights reserved.

  4. Optogenetic control of mitochondrial metabolism and Ca2+ signaling by mitochondria-targeted opsins.

    Science.gov (United States)

    Tkatch, Tatiana; Greotti, Elisa; Baranauskas, Gytis; Pendin, Diana; Roy, Soumitra; Nita, Luliaoana I; Wettmarshausen, Jennifer; Prigge, Matthias; Yizhar, Ofer; Shirihai, Orian S; Fishman, Daniel; Hershfinkel, Michal; Fleidervish, Ilya A; Perocchi, Fabiana; Pozzan, Tullio; Sekler, Israel

    2017-06-27

    Key mitochondrial functions such as ATP production, Ca 2+ uptake and release, and substrate accumulation depend on the proton electrochemical gradient (ΔμH + ) across the inner membrane. Although several drugs can modulate ΔμH + , their effects are hardly reversible, and lack cellular specificity and spatial resolution. Although channelrhodopsins are widely used to modulate the plasma membrane potential of excitable cells, mitochondria have thus far eluded optogenetic control. Here we describe a toolkit of optometabolic constructs based on selective targeting of channelrhodopsins with distinct functional properties to the inner mitochondrial membrane of intact cells. We show that our strategy enables a light-dependent control of the mitochondrial membrane potential (Δψ m ) and coupled mitochondrial functions such as ATP synthesis by oxidative phosphorylation, Ca 2+ dynamics, and respiratory metabolism. By directly modulating Δψ m , the mitochondria-targeted opsins were used to control complex physiological processes such as spontaneous beats in cardiac myocytes and glucose-dependent ATP increase in pancreatic β-cells. Furthermore, our optometabolic tools allow modulation of mitochondrial functions in single cells and defined cell regions.

  5. Gut microbiota controls adipose tissue expansion, gut barrier and glucose metabolism: novel insights into molecular targets and interventions using prebiotics.

    Science.gov (United States)

    Geurts, L; Neyrinck, A M; Delzenne, N M; Knauf, C; Cani, P D

    2014-03-01

    Crosstalk between organs is crucial for controlling numerous homeostatic systems (e.g. energy balance, glucose metabolism and immunity). Several pathological conditions, such as obesity and type 2 diabetes, are characterised by a loss of or excessive inter-organ communication that contributes to the development of disease. Recently, we and others have identified several mechanisms linking the gut microbiota with the development of obesity and associated disorders (e.g. insulin resistance, type 2 diabetes, hepatic steatosis). Among these, we described the concept of metabolic endotoxaemia (increase in plasma lipopolysaccharide levels) as one of the triggering factors leading to the development of metabolic inflammation and insulin resistance. Growing evidence suggests that gut microbes contribute to the onset of low-grade inflammation characterising these metabolic disorders via mechanisms associated with gut barrier dysfunctions. We have demonstrated that enteroendocrine cells (producing glucagon-like peptide-1, peptide YY and glucagon-like peptide-2) and the endocannabinoid system control gut permeability and metabolic endotoxaemia. Recently, we hypothesised that specific metabolic dysregulations occurring at the level of numerous organs (e.g. gut, adipose tissue, muscles, liver and brain) rely from gut microbiota modifications. In this review, we discuss the mechanisms linking gut permeability, adipose tissue metabolism, and glucose homeostasis, and recent findings that show interactions between the gut microbiota, the endocannabinoid system and the apelinergic system. These specific systems are discussed in the context of the gut-to-peripheral organ axis (intestine, adipose tissue and brain) and impacts on metabolic regulation. In the present review, we also briefly describe the impact of a variety of non-digestible nutrients (i.e. inulin-type fructans, arabinoxylans, chitin glucans and polyphenols). Their effects on the composition of the gut microbiota and

  6. Air traffic control : good progress on interim replacement for outage-plagued system, but risks can be further reduced

    Science.gov (United States)

    1996-10-01

    Certain air traffic control(ATC) centers experienced a series of major outages, : some of which were caused by the Display Channel Complex or DCC-a mainframe : computer system that processes radar and other data into displayable images on : controlle...

  7. [Metabolic parameters in patients with steatosis non alcoholic liver and controlled diabetes type 2 versus uncontrolled diabetes type 2].

    Science.gov (United States)

    Miranda Manrique, Gonzalo

    2016-01-01

    Non-alcoholic fatty liver (NASH) is widely distributed around the world and is more common in subjects with dyslipidemia, metabolic syndrome obese and DM2 (34-74%). However, the prevalence of cirrhosis by NASH in general population is unknown which is still subject of research. To determine if there are significant differences between metabolic parameters of non-alcoholic fatty liver in controlled versus uncontrolled diabetes type 2 of recent diagnosis. retrospective case-control study, performed in the Hospital Guillermo Almenara Irigoyen, Lima, Peru from November 2014 to February 2015.This study included 231 patients: 147 patients (NASH with DM2 of recent diagnosis and poor control) and 84 patients (NASH with DM2 ofrecent diagnosis and adequate control). Levene test for evaluating homogeneity of variances intra groups and parametric test for independent samples. After applying Levene test of homogeneity and student test, significant metabolic parameters were the triglycerides, HbA1C level, metformin dose and gender. It is important in diabetic patients to diagnose NASH early for a tighter control, not only of glucose but other metabolic parameters mainly triglycerides which strongly supports existing concept of "multiple hits" which considers NASH affects glucose homeostasis, and it could be the starting point of new research to improve interventions for decreasing progression from to cirrhosis in diabetic patients and also to delay progression of diabetes mellitus in patients with non alcoholic steatohepatitis.

  8. The Good, the Bad and the Ugly - Interacting Physical, Biogeochemical and Biolological Controls of Nutrient Cycling at Ecohydrological Interfaces

    Science.gov (United States)

    Krause, S.; Baranov, V. A.; Lewandowski, J.; Blaen, P. J.; Romeijn, P.

    2016-12-01

    The interfaces between streams, lakes and their bed sediments have for a long time been in the research focus of ecohydrologists, aquatic ecologists and biogeochemists. While over the past decades, critical understanding has been gained of the spatial patterns and temporal dynamics in nutrient cycling at sediment-freshwater interfaces, important question remain as to the actual drivers (physical, biogeochemical and biological) of the often observed hot spots and hot moments of nutrient cycling at these highly reactive systems. This study reports on a combination of laboratory manipulation, artificial stream and field experiments from reach to river network scales to investigate the interplay of physical, biogeochemical and biological drivers of interface nutrient cycling under the impact of and resilience to global environmental change. Our results indicate that biogeochemical hotspots at sediment-freshwater interfaces were controlled not only by reactant mixing ratios and residence time distributions, but strongly affected by patterns in streambed physical properties and bioavailability of organic carbon. Lab incubation experiments revealed that geology, and in particular organic matter content strongly controlled the magnitude of enhanced streambed greenhouse gas production caused by increasing water temperatures. While these findings help to improve our understanding of physical and biogeochemical controls on nutrient cycling, we only start to understand to what degree biological factors can enhance these processes even further. We found that for instance chironomid or brittle star facilitated bioturbation in has the potential to substantially enhance freshwater or marine sediment pore-water flow and respiration. We revealed that ignorance of these important biologically controls on physical exchange fluxes can lead to critical underestimation of whole system respiration and its increase under global environmental change.

  9. Antinociceptive effects, metabolism and disposition of ketamine in ponies under target-controlled drug infusion

    International Nuclear Information System (INIS)

    Knobloch, M.; Portier, C.J.; Levionnois, O.L.; Theurillat, R.; Thormann, W.; Spadavecchia, C.; Mevissen, M.

    2006-01-01

    Ketamine is widely used as an anesthetic in a variety of drug combinations in human and veterinary medicine. Recently, it gained new interest for use in long-term pain therapy administered in sub-anesthetic doses in humans and animals. The purpose of this study was to develop a physiologically based pharmacokinetic (PBPk) model for ketamine in ponies and to investigate the effect of low-dose ketamine infusion on the amplitude and the duration of the nociceptive withdrawal reflex (NWR). A target-controlled infusion (TCI) of ketamine with a target plasma level of 1 μg/ml S-ketamine over 120 min under isoflurane anesthesia was performed in Shetland ponies. A quantitative electromyographic assessment of the NWR was done before, during and after the TCI. Plasma levels of R-/S-ketamine and R-/S-norketamine were determined by enantioselective capillary electrophoresis. These data and two additional data sets from bolus studies were used to build a PBPk model for ketamine in ponies. The peak-to-peak amplitude and the duration of the NWR decreased significantly during TCI and returned slowly toward baseline values after the end of TCI. The PBPk model provides reliable prediction of plasma and tissue levels of R- and S-ketamine and R- and S-norketamine. Furthermore, biotransformation of ketamine takes place in the liver and in the lung via first-pass metabolism. Plasma concentrations of S-norketamine were higher compared to R-norketamine during TCI at all time points. Analysis of the data suggested identical biotransformation rates from the parent compounds to the principle metabolites (R- and S-norketamine) but different downstream metabolism to further metabolites. The PBPk model can provide predictions of R- and S-ketamine and norketamine concentrations in other clinical settings (e.g. horses)

  10. Metabolic and hormonal effects of caffeine: randomized, double-blind, placebo-controlled crossover trial.

    Science.gov (United States)

    MacKenzie, Todd; Comi, Richard; Sluss, Patrick; Keisari, Ronit; Manwar, Simone; Kim, Janice; Larson, Robin; Baron, John A

    2007-12-01

    In short-term studies, caffeine has been shown to increase insulin levels, reduce insulin sensitivity, and increase cortisol levels. However, epidemiological studies have indicated that long-term consumption of beverages containing caffeine such as coffee and green tea is associated with a reduced risk of type 2 diabetes mellitus. There is a paucity of randomized studies addressing the metabolic and hormonal effects of consuming caffeine over periods of more than 1 day. We evaluated the effect of oral intake of 200 mg of caffeine taken twice a day for 7 days on glucose metabolism, as well as on serum cortisol, dehydroepiandrosterone (DHEA), and androstenedione, and on nighttime salivary melatonin. A double-blind, randomized, placebo-controlled crossover study with periods of 7 days and washouts of 5 days comparing caffeine with placebo capsules was conducted. Participants were 16 healthy adults aged 18 to 22 years with a history of caffeine consumption. Blood samples from each subject were assayed for glucose, insulin, serum cortisol, DHEA, and androstenedione on the eighth day of each period after an overnight fast. Nighttime salivary melatonin was also measured. Insulin levels were significantly higher (by 1.80 microU/mL; 95% confidence interval, 0.33-3.28) after caffeine intake than after placebo. The homeostasis model assessment index of insulin sensitivity was reduced by 35% (95% confidence interval, 7%-62%) by caffeine. There were no differences in glucose, DHEA, androstenedione, and melatonin between treatment periods. This study provides evidence that daily caffeine intake reduces insulin sensitivity; the effect persists for at least a week and is evident up to 12 hours after administration.

  11. Second VdTUeV forum on nuclear engineering: Control is good, but trust is better? Lectures

    International Nuclear Information System (INIS)

    2009-01-01

    Within the 2nd VdTUeV Forum of Verband der TUeV e.V. (Berlin, Federal Republic of Germany) between 16th and 17th March, 2009, in Berlin (Federal Republic of Germany), the following lectures were held: (1) Nuclear power supervision and management responsibilities (H. Koerner); (2) Gain in safety by increasing the management responsibilities and reduction of the governmental control? (G. Hennenhoefer); (3) Experiences and results from the IRRS mission from the view of government (O. Groezinger); (4) The ethics of trust - Chances and limits (U.D. Pose); (5) It is dangerous to cross the line: Challenges for nature, humans and technology (K.J. Jahn); (5) Fundamental requirements on design, setup, development and application of IAEA safety standards (H. Liemersdorf); (6) International state of safety requirements and their national implementation (C. Wassilew); (7) Effects of modified requirements of a new regulatory framework for operating plants in an international comparison (M. Micklinghoff); (8) International requirements for prolongation of lifetime of nuclear power plants (R. Wernicke); (9) Digital control system in reactor protection systems, effects of the requirements of VdTUeV (U. Waas); (10) Safety aspects of dissimilar control systems (G.E. Langer); (11) OSA as an instrument for a holistic evaluation of safety (H. Pamme); (12) Safety relevant recognitions from an assessment of a PSA (C. Spitzner).

  12. Impact of Voglibose on of Metabolic Control Indicators in Patients with Diabetes Mellitus Type 1

    Directory of Open Access Journals (Sweden)

    V.I. Pankiv

    2015-02-01

    Full Text Available New therapeutic options to control diabetes mellitus (DM emerged with the discovery of alpha-glucosidase inhibitors which slow the absorption of carbohydrates in the small intestine. The objective of the study — to investigate the effect of voglibose administration on parameters of glycemic control, lipid metabolism and tolerability in patients with DM type 1. Materials and Methods. Criteria for inclusion in the study: DM type 1, age from 26 to 48 years, the level of glycated hemoglobin (HbA1c from 8 to 9 %. 19 patients were examined (7 men and 12 women, mean age 37.2 ± ± 3.9 years, DM duration 8.5 ± 1.4 years. Results. During the follow-up period (12 weeks, the level of HbA1c significantly decreased from 9.4 ± 0.6 % to 7.8 ± 0.4 % (p < 0.05. On the background of additional administration of voglibose, we observed a significant reduction in fasting glucose level from 10.37 ± 0.36 mmol/l to 7.39 ± 0.28 mmol/l (p < 0.01 and postprandial — from 12.29 ± 1.42 mmol/l to 8.46 ± 0.64 mmol/l (p < 0.01. At that, we have noted a significant reduction of total cholesterol (from 5.83 ± 0.11 mmol/l to 5.38 ± 0.08 mmol/l, p < 0.05, triglycerides (from 1.82 ± 0.03 mmol/l to 1.46 ± 0.03 mmol/l, p < 0.05 and low-density lipoprotein cholesterol (from 3.41 ± 0.05 mmol/l to 3.37 ± ± 0.04 mmol/l, p < 0.05. There were no significant changes in high-density lipoprotein cholesterol parameters. In two surveyed persons, we have detected adverse effects (bloating, which did not require discontinuation of therapy. Conclusion. Additional administration of voglibose at a dose of 0.9 mg/day on a background of insulin therapy helps to improve glycemic control and lipid metabolism, to reduce the daily dose of exogenous insulin and hypoglycemic reactions incidence in patients with DM type 1.

  13. Effect of Acarbose on Control of Metabolic Parameters in Patients with Diabetes Type 1

    Directory of Open Access Journals (Sweden)

    A. Ziaee

    2012-07-01

    Full Text Available Introduction & Objective: Acarbose is an intestinal alpha-glucosidase inhibitor that delays absorption of carbohydrates. Findings of some studies show that it has been effective in better control of blood glucose in patients with diabetes type 1. The goal of this study is to investigate the effect of administration of acarbose on glycemic & lipid parameters and daily insulin requirements and tolerability in type 1 diabetic patient.Materials & Methods: This was a clinical trial randomized double blind placebo controlled study. Performed on patients with history of at least 1 year diabetes type 1 and had HbA1c≥7.5%. Patients with Cr≥2, partial GI obstruction or IBD were excluded from the study. 45 patients were randomized to be administered acarbose or placebo for 12 weeks. Initial dose of acarbose was 25 mg T.D.S for 2 weeks, and then it was increased to 50 mg T.D.S for 10 weeks. BMI, FBS, 2hpp, HbA1c, Total cholesterol, HDL, LDL, TG and Insulin dosage were investigated monthly.Results: The values of BMI, FBS, 2hpp, HbA1c, Total cholesterol, and TG & Insulin requirements decreased significantly in the case group compared to the controls (P=0.003, P=0.005, P<0.001, P=0.001, P=0.003, P<0.001, P<0.001, respectively; but no significant changes were observed in HDL &LDL levels. Conclusion: Administration of acarbose together with insulin to type 1 diabetic patient can be valuable in improving metabolic control (BMI, FBS, 2hpp, HbA1c, Total cholesterol and TG.(Sci J Hamadan Univ Med Sci 2012;19(2:5-10

  14. Metabolic control targets in Sudanese adults with type 1 diabetes: A population-based study

    Directory of Open Access Journals (Sweden)

    Ahmed O Almobarak

    2017-01-01

    Full Text Available Background: Type 1 diabetes is a challenging metabolic disorder for health authorities in Sudan. The objective of this study was to assess the level of glycemic control and to determine the prevalence of dyslipidemia and complications among individuals with type 1 diabetes in Sudan. Materials and Methods: Individuals with type 1 diabetes, who were having the disease for at least 1 year, were invited to participate in this study. Data were collected from two diabetes centers, in the Capital Khartoum and Atbara City, North of Sudan. Participants were interviewed using standardized pretested questionnaire to record medical history, sociodemographic data, and life style characteristics. Blood pressure, body mass index, and waist circumference were measured. Blood samples were taken for measurement of lipid profile and glycosylated hemoglobin. Results: A total of eighty individuals with type 1 diabetes volunteered to participate in this study, 37.5% of males and 62.5% of females. Majority of the patients were aged between 40 and 70 years old. There was poor glycemic control (glycosylated hemoglobin> 7%, in 83.8%. Age and sex were significant factors associated with poor glycemic control in this cohort. High cholesterol, triglyceride, and low density lipoprotein were seen in 76.2%, 27.5%, and 48.8% of participants, respectively. Low high density lipoprotein was seen in 33.8%. Hypertension was determined in 21.3%. Peripheral neuropathy, visual impairment, diabetic foot, and myocardial infarction were seen in 50%, 48.8%, 18.8%, and 2.5% of patients, respectively. Conclusion: Sudanese adults with type 1 diabetes have poor glycemic control, high prevalence of dyslipidemia, and long-term complications.

  15. Purine-Metabolizing Ectoenzymes Control IL-8 Production in Human Colon HT-29 Cells

    Directory of Open Access Journals (Sweden)

    Fariborz Bahrami

    2014-01-01

    Full Text Available Interleukin-8 (IL-8 plays key roles in both chronic inflammatory diseases and tumor modulation. We previously observed that IL-8 secretion and function can be modulated by nucleotide (P2 receptors. Here we investigated whether IL-8 release by intestinal epithelial HT-29 cells, a cancer cell line, is modulated by extracellular nucleotide metabolism. We first identified that HT-29 cells regulated adenosine and adenine nucleotide concentration at their surface by the expression of the ectoenzymes NTPDase2, ecto-5′-nucleotidase, and adenylate kinase. The expression of the ectoenzymes was evaluated by RT-PCR, qPCR, and immunoblotting, and their activity was analyzed by RP-HPLC of the products and by detection of Pi produced from the hydrolysis of ATP, ADP, and AMP. In response to poly (I:C, with or without ATP and/or ADP, HT-29 cells released IL-8 and this secretion was modulated by the presence of NTPDase2 and adenylate kinase. Taken together, these results demonstrate the presence of 3 ectoenzymes at the surface of HT-29 cells that control nucleotide levels and adenosine production (NTPDase2, ecto-5′-nucleotidase and adenylate kinase and that P2 receptor-mediated signaling controls IL-8 release in HT-29 cells which is modulated by the presence of NTPDase2 and adenylate kinase.

  16. Exploring polyamine metabolism of Alternaria alternata to target new substances to control the fungal infection.

    Science.gov (United States)

    Estiarte, N; Crespo-Sempere, A; Marín, S; Sanchis, V; Ramos, A J

    2017-08-01

    Polyamines are essential for all living organisms as they are involved in several vital cell functions. The biosynthetic pathway of polyamines and its regulation is well established and, in this sense, the ornithine descarboxylase (ODC) enzyme acts as one of the controlling factors of the entire pathway. In this work we assessed the inhibition of the ODC with D, l-α-difluoromethylornithine (DFMO) on Alternaria alternata and we observed that fungal growth and mycotoxin production were reduced. This inhibition was not completely restored by the addition of exogenous putrescine. Actually, increasing concentrations of putrescine on the growth media negatively affected mycotoxin production, which was corroborated by the downregulation of pksJ and altR, both genes involved in mycotoxin biosynthesis. We also studied the polyamine metabolism of A. alternata with the goal of finding new targets that compromise its growth and its mycotoxin production capacity. In this sense, we tested two different polyamine analogs, AMXT-2455 and AMXT-3016, and we observed that they partially controlled A. alternata's viability in vitro and in vivo using tomato plants. Finding strategies to design new fungicide substances is becoming a matter of interest as resistance problems are emerging. Copyright © 2017. Published by Elsevier Ltd.

  17. Control of fluxes towards antibiotics and the role of primary metabolism in production of antibiotics

    DEFF Research Database (Denmark)

    Gunnarsson, Nina; Eliasson Lantz, Anna; Nielsen, Jacob

    2004-01-01

    Yield improvements in antibiotic-producing strains have classically been obtained through random mutagenesis and screening. An attractive alternative to this strategy is the rational design of producer strains via metabolic engineering, an approach that offers the possibility to increase yields...... in the metabolic network. Here we describe and discuss available methods for identification of these steps, both in antibiotic biosynthesis pathways and in the primary metabolism, which serves as the supplier of precursors and cofactors for the secondary metabolism. Finally, the importance of precursor...... and cofactor supply from primary metabolism in the biosynthesis of different types of antibiotics is discussed and recent developments in metabolic engineering towards increased product yields in antibiotic producing strains are reviewed....

  18. NAD+ metabolism and the control of energy homeostasis - a balancing act between mitochondria and the nucleus

    Science.gov (United States)

    Cantó, Carles; Menzies, Keir; Auwerx, Johan

    2015-01-01

    NAD+ has emerged as a vital cofactor that can rewire metabolism, activate sirtuins and maintain mitochondrial fitness through mechanisms such as the mitochondrial unfolded protein response. This improved understanding of NAD+ metabolism revived interest in NAD+ boosting strategies to manage a wide spectrum of diseases, ranging from diabetes to cancer. In this review, we summarize how NAD+ metabolism links energy status with adaptive cellular and organismal responses and how this knowledge can be therapeutically exploited. PMID:26118927

  19. Endocrine control of bone and calcium metabolism. Vol. 8A - Formal sessions and abstracts

    International Nuclear Information System (INIS)

    Cohn, D.V.; Fujita, Takuo; Potts, J.T. Jr.; Talmage, R.V.

    1984-01-01

    This book contains papers of a conference about hormonal regulation of calcium metabolism. The pathophysiology and treatment of disorders of mineral metabolism is described in several chapters. A separate chapter is devoted to bone composition, development and remodelling. The same for the physiology of skeletal tissue. The other chapters deal with the secretion, metabolism and action of parathormone, vitamin D, calcitonin and new recognized calcium factors. refs.; figs.; tabs

  20. Metabolic control, self-care behaviors, and parenting in adolescents with type 1 diabetes: a correlational study.

    Science.gov (United States)

    Greene, Maia Stoker; Mandleco, Barbara; Roper, Susanne Olsen; Marshall, Elaine S; Dyches, Tina

    2010-01-01

    The purpose of this pilot study was to explore relationships among metabolic control, self-care behaviors, and parenting in adolescents with type 1 diabetes. Twenty-nine adolescents (mean age, 14.1 years) and their parents participated. Metabolic control was determined by an average of 4 A1C values taken prior to study enrollment; self-care behaviors were measured with a 12-item self-report questionnaire; parenting style was evaluated using the Parenting Practices Report. The mean for A1C values was 8.5%; the mean for overall self-care behaviors was 4.93 (5 = usually). Participants rated themselves highest on the self-care behaviors of giving insulin shots when indicated and adjusting insulin when eating a lot. They ranked themselves lowest on eating a low-fat diet and testing urine for ketones. Parents tended to be more authoritative in their approaches to parenting than either authoritarian or permissive. A significant relationship was found between authoritative mothering and adolescent self-care behaviors and metabolic control. Regression analyses controlling for age and length of time with diabetes confirmed the significance of these relationships. Authoritative fathering positively correlated with the self-care behaviors of monitoring blood glucose, taking insulin, and not skipping meals. A relationship was also noted between permissive parenting by mothers/fathers and poorer metabolic outcomes. However, the permissive parenting correlations did not remain significant when controlling for age and length of time with diabetes. Clinicians may help prevent declining participation in self-care behaviors and metabolic control in adolescents with type 1 diabetes by working with parents, particularly mothers, and encouraging authoritative parenting.

  1. Metabolic Syndrome Increases the Risk of Sudden Sensorineural Hearing Loss in Taiwan: A Case-Control Study.

    Science.gov (United States)

    Chien, Chen-Yu; Tai, Shu-Yu; Wang, Ling-Feng; Hsi, Edward; Chang, Ning-Chia; Wu, Ming-Tsang; Ho, Kuen-Yao

    2015-07-01

    Sudden sensorineural hearing loss has been reported to be associated with diabetes mellitus, hypertension, and hyperlipidemia in previous studies. The aim of this study was to examine whether metabolic syndrome increases the risk of sudden sensorineural hearing loss in Taiwan. A case-control study. Tertiary university hospital. We retrospectively investigated 181 cases of sudden sensorineural hearing loss and 181 controls from the Department of Otorhinolaryngology, Kaohsiung Medical University Hospital, in southern Taiwan from 2010 to 2012, comparing their clinical variables. We analyzed the relationship between metabolic syndrome and sudden sensorineural hearing loss. Metabolic syndrome was defined according to the National Cholesterol Education Program Adult Treatment Panel III with Asian modifications. The demographic and clinical characteristics, audiometry results, and outcome were reviewed. Subjects with metabolic syndrome had a 3.54-fold increased risk (95% confidence interval [CI] = 2.00-6.43, P diabetes mellitus, hypertension, and hyperlipidemia. With increases in the number of metabolic syndrome components, the risk of sudden sensorineural hearing loss increased (P for trend Vertigo was associated with a poor outcome (P = .02; 95% CI = 1.13~5.13, adjusted odds ratio = 2.39). The hearing loss pattern may influence the outcome of sudden sensorineural hearing loss (P Vertigo and total hearing loss were indicators of a poor outcome in sudden sensorineural hearing loss. © American Academy of Otolaryngology—Head and Neck Surgery Foundation 2015.

  2. Dynamic optimal control of homeostasis: an integrative system approach for modeling of the central nitrogen metabolism in Saccharomyces cerevisiae.

    Science.gov (United States)

    van Riel, N A; Giuseppin, M L; Verrips, C T

    2000-01-01

    The theory of dynamic optimal metabolic control (DOMC), as developed by Giuseppin and Van Riel (Metab. Eng., 2000), is applied to model the central nitrogen metabolism (CNM) in Saccharomyces cerevisiae. The CNM represents a typical system encountered in advanced metabolic engineering. The CNM is the source of the cellular amino acids and proteins, including flavors and potentially valuable biomolecules; therefore, it is also of industrial interest. In the DOMC approach the cell is regarded as an optimally controlled system. Given the metabolic genotype, the cell faces a control problem to maintain an optimal flux distribution in a changing environment. The regulation is based on strategies and balances feedback control of homeostasis and feedforward regulation for adaptation. The DOMC approach is an integrative, holistic approach, not based on mechanistic descriptions and (therefore) not biased by the variation present in biochemical and molecular biological data. It is an effective tool to structure the rapidly increasing amount of data on the function of genes and pathways. The DOMC model is used successfully to predict the responses of pulses of ammonia and glutamine to nitrogen-limited continuous cultures of a wild-type strain and a glutamine synthetase-negative mutant. The simulation results are validated with experimental data.

  3. Cerebral metabolism and vascular reactivity during breath-hold and hypoxic challenge in freedivers and healthy controls

    DEFF Research Database (Denmark)

    Vestergaard, Mark B.; Larsson, Henrik B.W.

    2017-01-01

    blood flow (CBF) and metabolic rate of oxygen (CMRO2), and magnetic resonance spectroscopy was used to measure the cerebral lactate, glutamate+glutamine, N-acetylaspartate and phosphocreatine+creatine concentrations in the occipital lobe. Fifteen freedivers and seventeen non-diver controls participated...

  4. What Is the Best Blood Sampling Time for Metabolic Control of Phenylalanine and Tyrosine Concentrations in Tyrosinemia Type 1 Patients?

    NARCIS (Netherlands)

    van Dam, Esther; Daly, Anne; Venema-Liefaard, Gineke; van Rijn, Margreet; Derks, Terry G J; McKiernan, Patrick J; Heiner-Fokkema, Rebecca; MacDonald, Anita; van Spronsen, Francjan J

    2017-01-01

    BACKGROUND: Treatment of hereditary tyrosinemia type 1 with nitisinone and phenylalanine and tyrosine restricted diet has largely improved outcome, but the best blood sampling time for assessment of metabolic control is not known. AIM: To study diurnal and day-to-day variation of phenylalanine and

  5. Teenage girls with type 1 diabetes have poorer metabolic control than boys and face more complications in early adulthood

    DEFF Research Database (Denmark)

    Samuelsson, Ulf; Anderzén, Johan; Gudbjörnsdottir, Soffia

    2016-01-01

    AIMS: To compare metabolic control between males and females with type 1 diabetes during adolescence and as young adults, and relate it to microvascular complications. METHODS: Data concerning 4000 adolescents with type 1 diabetes registered in the Swedish paediatric diabetes quality registry, an...

  6. How good is controlled attenuation parameter and fatty liver index for assessing liver steatosis in general population: correlation with ultrasound.

    Science.gov (United States)

    Carvalhana, Sofia; Leitão, Jorge; Alves, Ana C; Bourbon, Mafalda; Cortez-Pinto, Helena

    2014-07-01

    Liver steatosis measurement by controlled attenuation parameter (CAP) is a non-invasive method for diagnosing steatosis, based on transient elastography. Its usefulness as screening procedure for hepatic steatosis in general population has not been previously evaluated. The aim of this study was to evaluate the diagnostic accuracy of CAP and fatty liver index (FLI) for detection and quantification of steatosis in general population. Recruitment was done from a prospective epidemiological study of the general adult population. Steatosis was evaluated using CAP, FLI and ultrasound (US). Steatosis scored according to Hamaguchi's US scoring, from 0 (S0) to 6 (S6) points. Hepatic steatosis defined by score ≥2 (S≥2) and moderate/severe steatosis by score ≥4 (S≥4). Performance of CAP and FLI for diagnosing steatosis compared with US was assessed using areas under receiver operating characteristic curves (AUROC). From 219 consecutive individuals studied, 13 (5.9%) excluded because of failure/unreliable liver stiffness measurements. Steatosis prevalence: S≥2 38.4% and S≥4 12.1%. CAP significantly correlated with steatosis (ρ = 0.73, P steatosis score (ρ = 0.76; P steatosis quantification in the general population. Larger studies are needed for validation. © 2013 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

  7. Eating patterns in adolescents with type 1 diabetes: Associations with metabolic control, insulin omission, and eating disorder pathology.

    Science.gov (United States)

    Wisting, Line; Reas, Deborah Lynn; Bang, Lasse; Skrivarhaug, Torild; Dahl-Jørgensen, Knut; Rø, Øyvind

    2017-07-01

    The purpose of this study was to investigate eating patterns among male and female adolescents with type 1 diabetes (T1D), and the associations with age, zBMI, eating disorder (ED) pathology, intentional insulin omission, and metabolic control. The sample consisted of 104 adolescents (58.6% females) with child-onset T1D, mean age of 15.7 years (SD 1.8) and mean zBMI of 0.4 (SD 0.8). The Child Eating Disorder Examination (ChEDE) assessed meal/snack frequency and ED pathology. T1D clinical data was obtained from the Norwegian Childhood Diabetes Registry. A significantly lower proportion of females than males (73.8% vs 97.7%) consumed breakfast on a daily basis. Approximately 50% of both genders ate lunch and 90% ate dinner daily. Among females, skipping breakfast was significantly associated with higher global ED psychopathology, shape concerns, self-induced vomiting, binge eating, insulin omission due to shape/weight concerns, and poorer metabolic control. Less frequent lunch consumption was significantly associated with poorer metabolic control. Skipping dinner was significantly associated with older age, higher dietary restraint, eating concerns, self-induced vomiting, and insulin omission. Among males, less frequent consumption of lunch and evening snacks was associated with attitudinal features of ED, including shape/weight concerns and dietary restraint. Among adolescents with T1D, irregular or infrequent meal consumption appears to signal potential ED pathology, as well as being associated with poorer metabolic control. These findings suggest the importance of routinely assessing eating patterns in adolescents with T1D to improve detection of ED pathology and to facilitate improved metabolic control and the associated risk of somatic complications. Copyright © 2017 Elsevier Ltd. All rights reserved.

  8. Overview on sugar metabolism and its control in Lactococcus lactis - The input from in vivo NMR

    NARCIS (Netherlands)

    Neves, AR; Pool, WA; Kok, J; Kuipers, OP; Santos, H; Neves, Ana Rute; Pool, Wietske A.

    The wide application of lactic acid bacteria in the production of fermented foods depends to a great extent on the unique features of sugar metabolism in these organisms. The relative metabolic simplicity and the availability of genetic tools made Lactococcus lactis the organism of choice to gain

  9. Determining the Control Circuitry of Redox Metabolism at the Genome-Scale

    DEFF Research Database (Denmark)

    Federowicz, Stephen; Kim, Donghyuk; Ebrahim, Ali

    2014-01-01

    -scale metabolic model to show that ArcA and Fnr regulate >80% of total metabolic flux and 96% of differential gene expression across fermentative and nitrate respiratory conditions. Based on the data, we propose a feedforward with feedback trim regulatory scheme, given the extensive repression of catabolic genes...

  10. Controlled sumoylation of the mevalonate pathway enzyme HMGS-1 regulates metabolism during aging

    NARCIS (Netherlands)

    Sapir, Amir; Tsur, Assaf; Koorman, Thijs; Ching, Kaitlin; Mishra, Prashant; Bardenheier, Annabelle; Podolsky, Lisa; Bening-Abu-Shach, Ulrike; Boxem, Mike; Chou, Tsui-Fen; Broday, Limor; Sternberg, Paul W

    2014-01-01

    Many metabolic pathways are critically regulated during development and aging but little is known about the molecular mechanisms underlying this regulation. One key metabolic cascade in eukaryotes is the mevalonate pathway. It catalyzes the synthesis of sterol and nonsterol isoprenoids, such as

  11. Cerebral Metabolism and the Role of Glucose Control in Acute Traumatic Brain Injury.

    Science.gov (United States)

    Buitrago Blanco, Manuel M; Prashant, Giyarpuram N; Vespa, Paul M

    2016-10-01

    This article reviews key concepts of cerebral glucose metabolism, neurologic outcomes in clinical trials, the biology of the neurovascular unit and its involvement in secondary brain injury after traumatic brain insults, and current scientific and clinical data that demonstrate a better understanding of the biology of metabolic dysfunction in the brain, a concept now known as cerebral metabolic energy crisis. The use of neuromonitoring techniques to better understand the pathophysiology of the metabolic crisis is reviewed and a model that summarizes the triphasic view of cerebral metabolic disturbance supported by existing scientific data is outlined. The evidence is summarized and a template for future research provided. Copyright © 2016 Elsevier Inc. All rights reserved.

  12. Epigenetic control and the circadian clock: linking metabolism to neuronal responses.

    Science.gov (United States)

    Orozco-Solis, R; Sassone-Corsi, P

    2014-04-04

    Experimental and epidemiological evidence reveal the profound influence that industrialized modern society has imposed on human social habits and physiology during the past 50 years. This drastic change in life-style is thought to be one of the main causes of modern diseases including obesity, type 2 diabetes, mental illness such as depression, sleep disorders, and certain types of cancer. These disorders have been associated to disruption of the circadian clock, an intrinsic time-keeper molecular system present in virtually all cells and tissues. The circadian clock is a key element in homeostatic regulation by controlling a large array of genes implicated in cellular metabolism. Importantly, intimate links between epigenetic regulation and the circadian clock exist and are likely to prominently contribute to the plasticity of the response to the environment. In this review, we summarize some experimental and epidemiological evidence showing how environmental factors such as stress, drugs of abuse and changes in circadian habits, interact through different brain areas to modulate the endogenous clock. Furthermore we point out the pivotal role of the deacetylase silent mating-type information regulation 2 homolog 1 (SIRT1) as a molecular effector of the environment in shaping the circadian epigenetic landscape. Published by Elsevier Ltd.

  13. New inducible genetic method reveals critical roles of GABA in the control of feeding and metabolism.

    Science.gov (United States)

    Meng, Fantao; Han, Yong; Srisai, Dollada; Belakhov, Valery; Farias, Monica; Xu, Yong; Palmiter, Richard D; Baasov, Timor; Wu, Qi

    2016-03-29

    Currently available inducible Cre/loxP systems, despite their considerable utility in gene manipulation, have pitfalls in certain scenarios, such as unsatisfactory recombination rates and deleterious effects on physiology and behavior. To overcome these limitations, we designed a new, inducible gene-targeting system by introducing an in-frame nonsense mutation into the coding sequence of Cre recombinase (nsCre). Mutant mRNAs transcribed from nsCre transgene can be efficiently translated into full-length, functional Cre recombinase in the presence of nonsense suppressors such as aminoglycosides. In a proof-of-concept model, GABA signaling from hypothalamic neurons expressing agouti-related peptide (AgRP) was genetically inactivated within 4 d after treatment with a synthetic aminoglycoside. Disruption of GABA synthesis in AgRP neurons in young adult mice led to a dramatic loss of body weight due to reduced food intake and elevated energy expenditure; they also manifested glucose intolerance. In contrast, older mice with genetic inactivation of GABA signaling by AgRP neurons had only transient reduction of feeding and body weight; their energy expenditure and glucose tolerance were unaffected. These results indicate that GABAergic signaling from AgRP neurons plays a key role in the control of feeding and metabolism through an age-dependent mechanism. This new genetic technique will augment current tools used to elucidate mechanisms underlying many physiological and neurological processes.

  14. Application of metabolic controls for the maximization of lipid production in semicontinuous fermentation.

    Science.gov (United States)

    Xu, Jingyang; Liu, Nian; Qiao, Kangjian; Vogg, Sebastian; Stephanopoulos, Gregory

    2017-07-03

    Acetic acid can be generated through syngas fermentation, lignocellulosic biomass degradation, and organic waste anaerobic digestion. Microbial conversion of acetate into triacylglycerols for biofuel production has many advantages, including low-cost or even negative-cost feedstock and environmental benefits. The main issue stems from the dilute nature of acetate produced in such systems, which is costly to be processed on an industrial scale. To tackle this problem, we established an efficient bioprocess for converting dilute acetate into lipids, using the oleaginous yeast Yarrowia lipolytica in a semicontinuous system. The implemented design used low-strength acetic acid in both salt and acid forms as carbon substrate and a cross-filtration module for cell recycling. Feed controls for acetic acid and nitrogen based on metabolic models and online measurement of the respiratory quotient were used. The optimized process was able to sustain high-density cell culture using acetic acid of only 3% and achieved a lipid titer, yield, and productivity of 115 g/L, 0.16 g/g, and 0.8 g⋅L -1 ⋅h -1 , respectively. No carbon substrate was detected in the effluent stream, indicating complete utilization of acetate. These results represent a more than twofold increase in lipid production metrics compared with the current best-performing results using concentrated acetic acid as carbon feed.

  15. Metabolic manipulation in chronic heart failure: study protocol for a randomised controlled trial

    Directory of Open Access Journals (Sweden)

    Leon Francisco

    2011-06-01

    Full Text Available Abstract Background Heart failure is a major cause of morbidity and mortality in society. Current medical therapy centres on neurohormonal modulation with angiotensin converting enzyme inhibitors and β-blockers. There is growing evidence for the use of metabolic manipulating agents as adjunctive therapy in patients with heart failure. We aim to determine the effect of perhexiline on cardiac energetics and alterations in substrate utilisation in patients with non-ischaemic dilated cardiomyopathy. Methods A multi-centre, prospective, randomised double-blind, placebo-controlled trial of 50 subjects with non-ischaemic dilated cardiomyopathy recruited from University Hospital Birmingham NHS Foundation Trust and Cardiff and Vale NHS Trust. Baseline investigations include magnetic resonance spectroscopy to assess cardiac energetic status, echocardiography to assess left ventricular function and assessment of symptomatic status. Subjects are then randomised to receive 200 mg perhexiline maleate or placebo daily for 4 weeks with serum drug level monitoring. All baseline investigations will be repeated at the end of the treatment period. A subgroup of patients will undergo invasive investigations with right and left heart catheterisation to calculate respiratory quotient, and mechanical efficiency. The primary endpoint is an improvement in the phosphocreatine to adenosine triphosphate ratio at 4 weeks. Secondary end points are: i respiratory quotient; ii mechanical efficiency; iii change in left ventricular (LV function. Trial Registration ClinicalTrials.gov: NCT00841139 ISRCTN: ISRCTN2887836

  16. Coordinations between gene modules control the operation of plant amino acid metabolic networks

    Directory of Open Access Journals (Sweden)

    Galili Gad

    2009-01-01

    Full Text Available Abstract Background Being sessile organisms, plants should adjust their metabolism to dynamic changes in their environment. Such adjustments need particular coordination in branched metabolic networks in which a given metabolite can be converted into multiple other metabolites via different enzymatic chains. In the present report, we developed a novel "Gene Coordination" bioinformatics approach and use it to elucidate adjustable transcriptional interactions of two branched amino acid metabolic networks in plants in response to environmental stresses, using publicly available microarray results. Results Using our "Gene Coordination" approach, we have identified in Arabidopsis plants two oppositely regulated groups of "highly coordinated" genes within the branched Asp-family network of Arabidopsis plants, which metabolizes the amino acids Lys, Met, Thr, Ile and Gly, as well as a single group of "highly coordinated" genes within the branched aromatic amino acid metabolic network, which metabolizes the amino acids Trp, Phe and Tyr. These genes possess highly coordinated adjustable negative and positive expression responses to various stress cues, which apparently regulate adjustable metabolic shifts between competing branches of these networks. We also provide evidence implying that these highly coordinated genes are central to impose intra- and inter-network interactions between the Asp-family and aromatic amino acid metabolic networks as well as differential system interactions with other growth promoting and stress-associated genome-wide genes. Conclusion Our novel Gene Coordination elucidates that branched amino acid metabolic networks in plants are regulated by specific groups of highly coordinated genes that possess adjustable intra-network, inter-network and genome-wide transcriptional interactions. We also hypothesize that such transcriptional interactions enable regulatory metabolic adjustments needed for adaptation to the stresses.

  17. G0/G1 Switch Gene 2 controls adipose triglyceride lipase activity and lipid metabolism in skeletal muscle

    Directory of Open Access Journals (Sweden)

    Claire Laurens

    2016-07-01

    Full Text Available Objective: Recent data suggest that adipose triglyceride lipase (ATGL plays a key role in providing energy substrate from triglyceride pools and that alterations of its expression/activity relate to metabolic disturbances in skeletal muscle. Yet little is known about its regulation. We here investigated the role of the protein G0/G1 Switch Gene 2 (G0S2, recently described as an inhibitor of ATGL in white adipose tissue, in the regulation of lipolysis and oxidative metabolism in skeletal muscle. Methods: We first examined G0S2 protein expression in relation to metabolic status and muscle characteristics in humans. We next overexpressed and knocked down G0S2 in human primary myotubes to assess its impact on ATGL activity, lipid turnover and oxidative metabolism, and further knocked down G0S2 in vivo in mouse skeletal muscle. Results: G0S2 protein is increased in skeletal muscle of endurance-trained individuals and correlates with markers of oxidative capacity and lipid content. Recombinant G0S2 protein inhibits ATGL activity by about 40% in lysates of mouse and human skeletal muscle. G0S2 overexpression augments (+49%, p < 0.05 while G0S2 knockdown strongly reduces (−68%, p < 0.001 triglyceride content in human primary myotubes and mouse skeletal muscle. We further show that G0S2 controls lipolysis and fatty acid oxidation in a strictly ATGL-dependent manner. These metabolic adaptations mediated by G0S2 are paralleled by concomitant changes in glucose metabolism through the modulation of Pyruvate Dehydrogenase Kinase 4 (PDK4 expression (5.4 fold, p < 0.001. Importantly, downregulation of G0S2 in vivo in mouse skeletal muscle recapitulates changes in lipid metabolism observed in vitro. Conclusion: Collectively, these data indicate that G0S2 plays a key role in the regulation of skeletal muscle ATGL activity, lipid content and oxidative metabolism. Keywords: Lipid metabolism, Skeletal muscle, Lipolysis, Adipose triglyceride lipase

  18. Developing a ubiquitous health management system with healthy diet control for metabolic syndrome healthcare in Taiwan.

    Science.gov (United States)

    Kan, Yao-Chiang; Chen, Kai-Hong; Lin, Hsueh-Chun

    2017-06-01

    Self-management in healthcare can allow patients managing their health data anytime and everywhere for prevention of chronic diseases. This study established a prototype of ubiquitous health management system (UHMS) with healthy diet control (HDC) for people who need services of metabolic syndrome healthcare in Taiwan. System infrastructure comprises of three portals and a database tier with mutually supportive components to achieve functionality of diet diaries, nutrition guides, and health risk assessments for self-health management. With the diet, nutrition, and personal health database, the design enables the analytical diagrams on the interactive interface to support a mobile application for diet diary, a Web-based platform for health management, and the modules of research and development for medical care. For database integrity, dietary data can be stored at offline mode prior to transformation between mobile device and server site at online mode. The UHMS-HDC was developed by open source technology for ubiquitous health management with personalized dietary criteria. The system integrates mobile, internet, and electronic healthcare services with the diet diary functions to manage healthy diet behaviors of users. The virtual patients were involved to simulate the self-health management procedure. The assessment functions were approved by capturing the screen snapshots in the procedure. The proposed system development was capable for practical intervention. This approach details the expandable framework with collaborative components regarding the self-developed UHMS-HDC. The multi-disciplinary applications for self-health management can support the healthcare professionals to reduce medical resources and improve healthcare effects for the patient who requires monitoring personal health condition with diet control. The proposed system can be practiced for intervention in the hospital. Copyright © 2017 Elsevier B.V. All rights reserved.

  19. Safety Assessment of Tocotrienol Supplementation in Subjects with Metabolic Syndrome: A Randomised Control Trial

    International Nuclear Information System (INIS)

    Lin, G.Y.; Ming, L.O.; Nesaratnam, K.; Kim-Tiu, T.; Selvaduray, K.R.; Meganathan, P.; Yen, F.J.

    2016-01-01

    Previous studies have reported that tocotrienols (T3) possess many distinct properties such as antioxidant, cardioprotective, neuroprotective, anti-cancer, anti-inflammatory and anti-angiogenic, which are beneficial for the improvement of human health. However, there is limited data available on the safety assessment of T3 compared to tocopherols (T). A randomised, double-blinded, cross-over and placebo-controlled human clinical trial was conducted to determine the safety and tolerance of T3 supplementation in 31 subjects with metabolic syndrome. The subjects were supplemented with tocotrienol-rich fra tion (TRF) 200 mg or placebo capsules twice daily for two weeks followed by a post-intervention visit. Results showed that T3 supplementation had no significant adverse effect on the red blood cell (RBC), white blood cell (WBC) and platelet counts between TRF (5.10 ± 0.78 x 10"1"2 litre"-"1, 7.35 ± 1.59 x 10"9 litre"-"1, 279.45 ± 73.86 x 10"9 litre"-"1, respectively) and placebo interventions (5.13 ± 0.76 x 10"1"2 litre"-"1, 7.25 ± 1.95 x 10"9 litre"-"1, 267.45 ± 68.72 x 10"9 litre"-"1, respectively). Measures of serum aspartate aminotransferase (AST), serum alanine aminotransferase (ALT)) and albumin did not differ between TRF (25.68 ± 10.72 IU litre"-"1, 38.26 ± 24.74 IU litre"-"1, 43.61 ± 2.26 g litre"-"1, respectively) and placebo interventions (27.39 ± 16.44 IU litre"-"1, 42.23 ± 33.58 IU litre"-"1, 43.68 ± 2.15 g litre"-"1, respectively).This study indicated that supplementation with T3 at the dosage of 400 mg per day for 14 days did not induce haematoxicity and hepatotoxicity in subjects with metabolic syndrome. (author)

  20. Luggage and shipped goods

    International Nuclear Information System (INIS)

    Vogel, H.; Haller, D.

    2007-01-01

    Summary: Purpose: Control of luggage and shipped goods are frequently carried out. The possibilities of X-ray technology shall be demonstrated. Materials and methods: There are different imaging techniques. The main concepts are transmission imaging, backscatter imaging, computed tomography, and dual energy imaging and the combination of different methods The images come from manufacturers and personal collections. Results: The search concerns mainly, weapons, explosives, and drugs; furthermore animals, and stolen goods, Special problems offer the control of letters and the detection of Improvised Explosive Devices (IED). Conclusion: One has to expect that controls will increase and that imaging with X-rays will have their part. Pattern recognition software will be used for analysis enforced by economy and by demand for higher efficiency - man and computer will produce more security than man alone

  1. Mineralogical controls on surface colonization by sulfur-metabolizing microbial communities

    Science.gov (United States)

    Jones, A. A.; Bennett, P.

    2012-12-01

    When characterizing microbial diversity and the microbial ecosystem of the shallow subsurface the mineral matrix is generally assumed to be homogenous and unreactive. We report here experimental evidence that microorganisms colonize rock surfaces according to the rock's chemistry and the organism's metabolic requirements and tolerances. We investigated this phenomenon using laboratory biofilm reactors with both a pure culture of sulfur-oxidizing Thiothrix unzii and a mixed environmental sulfur-metabolizing community from Lower Kane, Cave, WY, USA. Reactors contained rock and mineral chips (calcite, albite, microcline, quartz, chert, Madison Limestone (ML), Madison Dolostone (MD), and basalt) amended with one of the two inoculants. Biomass of attached microorganisms on each mineral surface was quantified. The 16S rRNA of attached microbial communities were compared using Roche FLX and Titanium 454 next generation pyrosequencing. A primary controlling factor on taxonomy of attached microorganisms in both pure and mixed culture experiments was mineral buffering capacity. In mixed culture experiments acid-buffering carbonates were preferentially colonized by neutrophilic sulfur-oxidizing microorganisms (~18% to ~27% of microorganisms), while acidophilic sulfur-oxidizing microorganisms colonized non-buffering quartz exclusively (~46% of microorganisms). The nutrient content of the rock was a controlling factor on biomass accumulation, with neutrophilic organisms selecting between carbonate surfaces of equivalent buffer capacities according to the availability of phosphate. Dry biomass on ML was 17.8 ± 2.3 mg/cm2 and MD was 20.6 ± 6.8 mg/cm2; while nutrient poor calcite accumulated 2.4 ± 0.3 mg/cm2. Biomass accumulation was minimal on non-buffering nutrient-limited surfaces. These factors are countered by the competitive exclusion of some populations. A pure culture of T. unzii preferentially colonizes carbonates while a very closely related Thiothrix spp is excluded

  2. Good manufacturing practice

    International Nuclear Information System (INIS)

    Schlyer, D.J.

    2001-01-01

    In this presentation author deals with the Implementation of good manufacturing practice for radiopharmaceuticals. The presentation is divided into next parts: Batch size; Expiration date; QC Testing; Environmental concerns; Personnel aspects; Radiation concerns; Theoretical yields; Sterilizing filters; Control and reconciliation of materials and components; Product strength; In process sampling and testing; Holding and distribution; Drug product inspection; Buildings and facilities; Renovations at BNL for GMP; Aseptic processing and sterility assurance; Process validation and control; Quality control and drug product stability; Documentation and other GMP topics; Building design considerations; Equipment; and Summary

  3. Nutritional Ketosis Affects Metabolism and Behavior in Sprague-Dawley Rats in Both Control and Chronic Stress Environments

    Directory of Open Access Journals (Sweden)

    Milene L. Brownlow

    2017-05-01

    Full Text Available Nutritional ketosis may enhance cerebral energy metabolism and has received increased interest as a way to improve or preserve performance and resilience. Most studies to date have focused on metabolic or neurological disorders while anecdotal evidence suggests that ketosis may enhance performance in the absence of underlying dysfunction. Moreover, decreased availability of glucose in the brain following stressful events is associated with impaired cognition, suggesting the need for more efficient energy sources. We tested the hypotheses that ketosis induced by endogenous or exogenous ketones could: (a augment cognitive outcomes in healthy subjects; and (b prevent stress-induced detriments in cognitive parameters. Adult, male, Sprague Dawley rats were used to investigate metabolic and behavioral outcomes in 3 dietary conditions: ketogenic (KD, ketone supplemented (KS, or NIH-31 control diet in both control or chronic stress conditions. Acute administration of exogenous ketones resulted in reduction in blood glucose and sustained ketosis. Chronic experiments showed that in control conditions, only KD resulted in pronounced metabolic alterations and improved performance in the novel object recognition test. The hypothalamic-pituitary-adrenal (HPA axis response revealed that KD-fed rats maintained peripheral ketosis despite increases in glucose whereas no diet effects were observed in ACTH or CORT levels. Both KD and KS-fed rats decreased escape latencies on the third day of water maze, whereas only KD prevented stress-induced deficits on the last testing day and improved probe test performance. Stress-induced decrease in hippocampal levels of β-hydroxybutyrate was attenuated in KD group while both KD and KS prevented stress effects on BDNF levels. Mitochondrial enzymes associated with ketogenesis were increased in both KD and KS hippocampal samples and both endothelial and neuronal glucose transporters were affected by stress but only in the

  4. Metabolic control after years of completing a clinical trial on sensor-augmented pump therapy.

    Science.gov (United States)

    Quirós, Carmen; Giménez, Marga; Orois, Aida; Conget, Ignacio

    2015-11-01

    Sensor-augmented pump (SAP) therapy has been shown to be effective and safe for improving metabolic control in patients with type 1 diabetes mellitus (T1DM) in a number of trials. Our objective was to assess glycemic control in a group of T1DM patients on insulin pump or SAP therapy after years of participating in the SWITCH (Sensing With Insulin pump Therapy To Control HbA1c) trial and their return to routine medical monitoring. A retrospective, observational study of 20 patients who participated in the SWITCH trial at our hospital from 2008 to 2010. HbA1c values were compared at the start, during (at the end of the periods with/without SAP use - Sensor On/Sensor Off period respectively - of the cross-over design), and 3 years after study completion. HbA1c values of patients who continued SAP therapy (n=6) or only used insulin pump (n=14) were also compared. Twenty patients with T1DM (44.4±9.3 years, 60% women, baseline HbA1c level 8.43±0.55%) were enrolled into the SWITCH study). Three years after study completion, HbA1c level was 7.79±0.77 in patients on pump alone, with no significant change from the value at the end of the Off period of the study (7.85±0.57%; p=0.961). As compared to the end of the On period, HbA1c worsened less in patients who remained on SAP than in those on pump alone (0.18±0.42 vs. 0.55±0.71%; p=0.171), despite the fact that levels were similar at study start (8.41±0.60 vs. 8.47±0.45; p=0.831) and at the end of the On period (7.24±0.48 vs. 7.38±0.61; p=0.566). Frequency of CGM use in patients who continued SAP therapy was high (61.2% of the time in the last 3 months). Our study suggests that the additional benefit of SAP therapy achieved in a clinical trial may persist in the long term in routine clinical care of patients with T1DM. Copyright © 2015 SEEN. Published by Elsevier España, S.L.U. All rights reserved.

  5. Synthetic biology and regulatory networks: where metabolic systems biology meets control engineering

    NARCIS (Netherlands)

    He, F.; Murabito, E.; Westerhoff, H.V.

    2016-01-01

    Metabolic pathways can be engineered to maximize the synthesis of various products of interest. With the advent of computational systems biology, this endeavour is usually carried out throughin silicotheoretical studies with the aim to guide and complement furtherin vitroandin vivoexperimental

  6. Metabolic Heat Regenerated Temperature Swing Adsorption for CO2, Thermal and Humidity Control, Phase I

    Data.gov (United States)

    National Aeronautics and Space Administration — Metabolic heat regenerated Temperature Swing Adsorption (MTSA) technology is proposed for a Portable Life Support System to remove and reject heat and carbon dioxide...

  7. Sympathetic nervous system control of triglyceride metabolism: novel concepts derived from recent studies

    NARCIS (Netherlands)

    Geerling, Janine J.; Boon, Mariëtte R.; Kooijman, Sander; Parlevliet, Edwin T.; Havekes, Louis M.; Romijn, Johannes A.; Meurs, Illiana M.; Rensen, Patrick C. N.

    2014-01-01

    Important players in triglyceride (TG) metabolism include the liver (production), white adipose tissue (WAT) (storage), heart and skeletal muscle (combustion to generate ATP), and brown adipose tissue (BAT) (combustion toward heat), the collective action of which determine plasma TG levels.

  8. The post-transcriptional regulatory system CSR controls the balance of metabolic pools in upper glycolysis of Escherichia coli.

    Science.gov (United States)

    Morin, Manon; Ropers, Delphine; Letisse, Fabien; Laguerre, Sandrine; Portais, Jean-Charles; Cocaign-Bousquet, Muriel; Enjalbert, Brice

    2016-05-01

    Metabolic control in Escherichia coli is a complex process involving multilevel regulatory systems but the involvement of post-transcriptional regulation is uncertain. The post-transcriptional factor CsrA is stated as being the only regulator essential for the use of glycolytic substrates. A dozen enzymes in the central carbon metabolism (CCM) have been reported as potentially controlled by CsrA, but its impact on the CCM functioning has not been demonstrated. Here, a multiscale analysis was performed in a wild-type strain and its isogenic mutant attenuated for CsrA (including growth parameters, gene expression levels, metabolite pools, abundance of enzymes and fluxes). Data integration and regulation analysis showed a coordinated control of the expression of glycolytic enzymes. This also revealed the imbalance of metabolite pools in the csrA mutant upper glycolysis, before the phosphofructokinase PfkA step. This imbalance is associated with a glucose-phosphate stress. Restoring PfkA activity in the csrA mutant strain suppressed this stress and increased the mutant growth rate on glucose. Thus, the carbon storage regulator system is essential for the effective functioning of the upper glycolysis mainly through its control of PfkA. This work demonstrates the pivotal role of post-transcriptional regulation to shape the carbon metabolism. © 2016 John Wiley & Sons Ltd.

  9. LA Sprouts Randomized Controlled Nutrition, Cooking and Gardening Program Reduces Obesity and Metabolic Risk in Latino Youth

    Science.gov (United States)

    Gatto, Nicole M.; Martinez, Lauren C.; Spruijt-Metz, Donna; Davis, Jaimie N.

    2015-01-01

    Objective To assess the effects of a 12-week gardening, nutrition, and cooking intervention (“LA Sprouts”) on dietary intake, obesity parameters and metabolic disease risk among low-income, primarily Hispanic/Latino youth in Los Angeles. Methods Randomized control trial involving four elementary schools [2 schools randomized to intervention (172, 3rd–5th grade students); 2 schools randomized to control (147, 3rd–5th grade students)]. Classes were taught in 90-minute sessions once a week to each grade level for 12 weeks. Data collected at pre- and post-intervention included dietary intake via food frequency questionnaire (FFQ), anthropometric measures [BMI, waist circumference (WC)], body fat, and fasting blood samples. Results LA Sprouts participants had significantly greater reductions in BMI z-scores (0.1 versus 0.04 point decrease, respectively; p=0.01) and WC (−1.2 cm vs. no change; p<0.001). Fewer LA Sprouts participants had the metabolic syndrome (MetSyn) after the intervention than before, while the number of controls with MetSyn increased. LA Sprouts participants had improvements in dietary fiber intake (+3.5% vs. −15.5%; p=0.04) and less decreases in vegetable intake (−3.6% vs. −26.4%; p=0.04). Change in fruit intake before and after the intervention did not significantly differ between LAS and control subjects. Conclusions LA Sprouts was effective in reducing obesity and metabolic risk. PMID:25960146

  10. [Blood-sugar self control. A means for the diabetic of controlling his metabolic management. Quality control of a battery-run pocket size reflectometer (glucose-meter)].

    Science.gov (United States)

    Leidinger, F; Jörgens, V; Chantelau, E; Berchtold, P; Berger, M

    1980-07-26

    Home blood glucose monitoring by diabetic patients has recently been advocated as an effective means to improve metabolic control. The Glucocheck apparatus, a pocket-size battery-driven reflectance-meter (in Germany commercially available under the name Glucose-meter), has been evaluated for accuracy and practicability. In 450 blood glucose measurements, the variance between the values obtained using the Glucocheck apparatus and routine clinical laboratory procedures was +/- 11.7%. Especially in the low range of blood glucose concentrations, the Glucocheck method was very reliable. The quantitative precision of the Glucocheck method depends, however, quite considerably on the ability of the patient to use the apparatus correctly. In order to profit from Glucocheck in clinical practice, particular efforts to educate the patients in its use are necessary.

  11. Randomized placebo control study of metformin in psoriasis patients with metabolic syndrome (systemic treatment cohort

    Directory of Open Access Journals (Sweden)

    Surjit Singh

    2017-01-01

    Full Text Available Background: Psoriasis has been found to be associated with obesity, metabolic syndrome (MS, diabetes, and cardiovascular risk factors. Metformin treatment showed improvement in cardiovascular risk factors and hyperinsulinemia. Objective: To evaluate the efficacy and safety of metformin in psoriasis patients with MS. Materials and Methods: This was a single-center, parallel-group, randomized, open-label study with blinded end point assessment of metformin (1000 mg once daily for 12 weeks; n = 20 and placebo (n = 18 in psoriasis patients with MS. Total sample size was 38 participants. Results: Statistically significant improvement was observed in mean percentage change in erythema, scaling, and induration (ESI (P = 0.048 in metformin as compared to placebo while mean percentage change in psoriasis area and severity index (PASI and physician global assessment (PGA scores was not significant (PASI - P = 0.215, PGA - P = 0.070. There was a statistically significant difference in percentage of parameters of MS improved following 12 weeks of treatment in metformin (19% as compared to placebo (8.9% group (P = 0.046. Statistically significant difference in percentage of patients achieving 75% reduction in ESI scores (P = 0.024. Significant improvement was observed in mean weight, body mass index (BMI, total cholesterol, and low-density lipoprotein (LDL cholesterol in metformin group as compared to placebo. Improvement in BMI, fasting plasma glucose, serum triglycerides, high-density lipoprotein, LDL, systolic blood pressure, diastolic blood pressure, and total cholesterol was statistically significant in metformin group over the period of 12 weeks. There was no significant difference in adverse events in two groups except weight gain. Conclusion: Metformin has shown improvement in psoriasis and parameters of MS, hence can be used for the benefit of psoriasis patients having MS. Large, controlled studies are needed to confirm.

  12. A recruiting protein of geranylgeranyl diphosphate synthase controls metabolic flux toward chlorophyll biosynthesis in rice.

    Science.gov (United States)

    Zhou, Fei; Wang, Cheng-Yuan; Gutensohn, Michael; Jiang, Ling; Zhang, Peng; Zhang, Dabing; Dudareva, Natalia; Lu, Shan

    2017-06-27

    In plants, geranylgeranyl diphosphate (GGPP) is produced by plastidic GGPP synthase (GGPPS) and serves as a precursor for vital metabolic branches, including chlorophyll, carotenoid, and gibberellin biosynthesis. However, molecular mechanisms regulating GGPP allocation among these biosynthetic pathways localized in the same subcellular compartment are largely unknown. We found that rice contains only one functionally active GGPPS, OsGGPPS1, in chloroplasts. A functionally active homodimeric enzyme composed of two OsGGPPS1 subunits is located in the stroma. In thylakoid membranes, however, the GGPPS activity resides in a heterodimeric enzyme composed of one OsGGPPS1 subunit and GGPPS recruiting protein (OsGRP). OsGRP is structurally most similar to members of the geranyl diphosphate synthase small subunit type II subfamily. In contrast to members of this subfamily, OsGRP enhances OsGGPPS1 catalytic efficiency and specificity of GGPP production on interaction with OsGGPPS1. Structural biology and protein interaction analyses demonstrate that affinity between OsGRP and OsGGPPS1 is stronger than between two OsGGPPS1 molecules in homodimers. OsGRP determines OsGGPPS1 suborganellar localization and directs it to a large protein complex in thylakoid membranes, consisting of geranylgeranyl reductase (OsGGR), light-harvesting-like protein 3 (OsLIL3), protochlorophyllide oxidoreductase (OsPORB), and chlorophyll synthase (OsCHLG). Taken together, genetic and biochemical analyses suggest OsGRP functions in recruiting OsGGPPS1 from the stroma toward thylakoid membranes, thus providing a mechanism to control GGPP flux toward chlorophyll biosynthesis.

  13. Metabolic syndrome and the risk of urothelial carcinoma of the bladder: a case-control study

    International Nuclear Information System (INIS)

    Montella, Maurizio; Di Maso, Matteo; Crispo, Anna; Grimaldi, Maria; Bosetti, Cristina; Turati, Federica; Giudice, Aldo; Libra, Massimo; Serraino, Diego; La Vecchia, Carlo; Tambaro, Rosa; Cavalcanti, Ernesta; Ciliberto, Gennaro; Polesel, Jerry

    2015-01-01

    The Metabolic syndrome (MetS) is an emerging condition worldwide, consistently associated with an increased risk of several cancers. Some information exists on urothelial carcinoma of the bladder (UCB) and MetS. This study aims at further evaluating the association between the MetS and UCB. Between 2003 and 2014 in Italy, we conducted a hospital-based case-control study, enrolling 690 incident UCB patients and 665 cancer-free matched patients. The MetS was defined as the presence of at least three of the four selected indicators: abdominal obesity, hypercholesterolemia, hypertension, and diabetes. Odds ratios (ORs) and corresponding 95 % confidence intervals (CIs) for MetS and its components were estimated through multiple logistic regression models, adjusting for potential confounders. Patients with MetS were at a 2-fold higher risk of UCB (95 % CI:1.38–3.19), compared to those without the MetS. In particular, ORs for bladder cancer were 2.20 (95 % CI:1.42–3.38) for diabetes, 0.88 (95 % CI: 0.66-1.17) for hypertension, 1.16 (95 % CI: 0.80-1.67) for hypercholesterolemia, and 1.63 (95 % CI:1.22–2.19) for abdominal obesity. No heterogeneity in risks emerged across strata of sex, age, education, geographical area, and smoking habits. Overall, 8.1 % (95 % CI: 3.9-12.4 %) of UCB cases were attributable to the MetS. This study supports a positive association between the MetS and bladder cancer risk

  14. CCR5 controls immune and metabolic functions during Toxoplasma gondii infection.

    Directory of Open Access Journals (Sweden)

    Giuliano Bonfá

    Full Text Available CCR5, an important receptor related to cell recruitment and inflammation, is expressed during experimental Toxoplasma gondii infection. However, its role in the immunopathology of toxoplasmosis is not clearly defined yet. Thus, we inoculated WT and CCR5(-/- mice with a sub lethal dose of the parasite by oral route. CCR5(-/- mice were extremely susceptible to infection, presenting higher parasite load and lower tissue expression of IL-12p40, IFN-γ, TNF, IL-6, iNOS, Foxp3, T-bet, GATA-3 and PPARα. Although both groups presented inflammation in the liver with prominent neutrophil infiltration, CCR5(-/- mice had extensive tissue damage with hepatocyte vacuolization, steatosis, elevated serum triglycerides and transaminases. PPARα agonist Gemfibrozil improved the vacuolization but did not rescue CCR5(-/- infected mice from high serum triglycerides levels and enhanced mortality. We also found intense inflammation in the ileum of CCR5(-/- infected mice, with epithelial ulceration, augmented CD4 and decreased frequency of NK cells in the gut lamina propria. Most interestingly, these findings were accompanied by an outstanding accumulation of neutrophils in the ileum, which seemed to be involved in the gut immunopathology, once the depletion of these cells was accompanied by reduced local damage. Altogether, these data demonstrated that CCR5 is essential to the control of T. gondii infection and to maintain the metabolic, hepatic and intestinal integrity. These findings add novel information on the disease pathogenesis and may be relevant for directing future approaches to the treatment of multi-deregulated diseases.

  15. Dimensionality controls cytoskeleton assembly and metabolism of fibroblast cells in response to rigidity and shape.

    Directory of Open Access Journals (Sweden)

    Mirjam Ochsner

    2010-03-01

    Full Text Available Various physical parameters, including substrate rigidity, size of adhesive islands and micro-and nano-topographies, have been shown to differentially regulate cell fate in two-dimensional (2-D cell cultures. Cells anchored in a three-dimensional (3-D microenvironment show significantly altered phenotypes, from altered cell adhesions, to cell migration and differentiation. Yet, no systematic analysis has been performed that studied how the integrated cellular responses to the physical characteristics of the environment are regulated by dimensionality (2-D versus 3-D.Arrays of 5 or 10 microm deep microwells were fabricated in polydimethylsiloxane (PDMS. The actin cytoskeleton was compared for single primary fibroblasts adhering either to microfabricated adhesive islands (2-D or trapped in microwells (3-D of controlled size, shape, and wall rigidity. On rigid substrates (Young's Modulus = 1 MPa, cytoskeleton assembly within single fibroblast cells occurred in 3-D microwells of circular, rectangular, square, and triangular shapes with 2-D projected surface areas (microwell bottom surface area and total surface areas of adhesion (microwell bottom plus wall surface area that inhibited stress fiber assembly in 2-D. In contrast, cells did not assemble a detectable actin cytoskeleton in soft 3-D microwells (20 kPa, regardless of their shapes, but did so on flat, 2-D substrates. The dependency on environmental dimensionality was also reflected by cell viability and metabolism as probed by mitochondrial activities. Both were upregulated in 3-D cultured cells versus cells on 2-D patterns when surface area of adhesion and rigidity were held constant.These data indicate that cell shape and rigidity are not orthogonal parameters directing cell fate. The sensory toolbox of cells integrates mechanical (rigidity and topographical (shape and dimensionality information differently when cell adhesions are confined to 2-D or occur in a 3-D space.

  16. Dental caries and salivary status in children with type 1 diabetes mellitus, related to the metabolic control of the disease.

    Science.gov (United States)

    Siudikiene, Jolanta; Machiulskiene, Vita; Nyvad, Bente; Tenovuo, Jorma; Nedzelskiene, Irena

    2006-02-01

    The aim of this study was to investigate the relationship among type 1 diabetes mellitus, dental caries, and salivary status in children. The study comprised 68, 10-15-yr-old diabetics, and 68, age- and gender-matched non-diabetic controls. Diabetics were categorized into well-to-moderately controlled (HbA1c or= 9.0%) groups. Caries was recorded by assessing lesion activity at non-cavitated and cavity levels. Teeth were examined visually for the presence of dental plaque. Saliva was analyzed for unstimulated and stimulated flow rates, buffer effect, mutans streptococci, lactobacilli, and yeasts. Diabetics had fewer caries and plaque, lower salivary flow rates and buffer effect, and more frequent growth of yeasts than their non-diabetic controls. Well-to-moderately controlled diabetics had fewer decayed surfaces and lower counts of mutans streptococci and yeasts than poorly controlled diabetics, but the level of metabolic control of diabetes had no influence on salivary flow rates and buffer effect. High caries levels in diabetics were significantly associated with age, plaque score, and decreased unstimulated salivary flow rate, but were not associated with the level of metabolic control of diabetes. High caries experience in this study population could be related to plaque accumulation and/or to changes in saliva induced by diabetes mellitus.

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

    Science.gov (United States)

    Rijpma, Anne; van der Graaf, Marinette; Lansbergen, Marieke M; Meulenbroek, Olga; Cetinyurek-Yavuz, Aysun; Sijben, John W; Heerschap, Arend; Olde Rikkert, Marcel G M

    2017-07-26

    Synaptic dysfunction contributes to cognitive impairment in Alzheimer's disease and may be countered by increased intake of nutrients that target brain phospholipid metabolism. In this study, we explored whether the medical food Souvenaid affects brain phospholipid metabolism in patients with Alzheimer's disease. Thirty-four drug-naive patients with mild Alzheimer's disease (Mini Mental State Examination score ≥20) were enrolled in this exploratory, double-blind, randomized controlled study. Before and after 4-week intervention with Souvenaid or an isocaloric control product, phosphorus and proton magnetic resonance spectroscopy (MRS) was performed to assess surrogate measures of phospholipid synthesis and breakdown (phosphomonoesters [PME] and phosphodiesters [PDEs]), neural integrity (N-acetyl aspartate), gliosis (myo-inositol), and choline metabolism (choline-containing compounds [tCho]). The main outcome parameters were PME and PDE signal intensities and the PME/PDE ratio. MRS data from 33 patients (60-86 years old; 42% males; Souvenaid arm n = 16; control arm n = 17) were analyzed. PME/PDE and tCho were higher after 4 weeks of Souvenaid compared with control (PME/PDE least squares [LS] mean difference [95% CI] 0.18 [0.06-0.30], p = 0.005; tCho LS mean difference [95% CI] 0.01 [0.00-0.02], p = 0.019). No significant differences were observed in the other MRS outcome parameters. MRS reveals that Souvenaid affects brain phospholipid metabolism in mild Alzheimer's disease, in line with findings in preclinical studies. Netherlands Trial Register, NTR3346 . Registered on 13 March 2012.

  18. Randomized controlled trial of a good practice approach to treatment of childhood obesity in Malaysia: Malaysian Childhood Obesity Treatment Trial (MASCOT).

    Science.gov (United States)

    Wafa, Sharifah W; Talib, Ruzita A; Hamzaid, Nur H; McColl, John H; Rajikan, Roslee; Ng, Lai O; Ramli, Ayiesah H; Reilly, John J

    2011-06-01

    Few randomized controlled trials (RCTs) of interventions for the treatment of childhood obesity have taken place outside the Western world. To test whether a good practice intervention for the treatment of childhood obesity would have a greater impact on weight status and other outcomes than a control condition in Kuala Lumpur, Malaysia. Assessor-blinded RCT of a treatment intervention in 107 obese 7- to 11-year olds. The intervention was relatively low intensity (8 hours contact over 26 weeks, group based), aiming to change child sedentary behavior, physical activity, and diet using behavior change counselling. Outcomes were measured at baseline and six months after the start of the intervention. Primary outcome was BMI z-score, other outcomes were weight change, health-related quality of life (Peds QL), objectively measured physical activity and sedentary behavior (Actigraph accelerometry over 5 days). The intervention had no significant effect on BMI z score relative to control. Weight gain was reduced significantly in the intervention group compared to the control group (+1.5 kg vs. +3.5 kg, respectively, t-test p < 0.01). Changes in health-related quality of life and objectively measured physical activity and sedentary behavior favored the intervention group. Treatment was associated with reduced rate of weight gain, and improvements in physical activity and quality of life. More substantial benefits may require longer term and more intensive interventions which aim for more substantive lifestyle changes.

  19. Orphan Nuclear Receptor ERRα Controls Macrophage Metabolic Signaling and A20 Expression to Negatively Regulate TLR-Induced Inflammation.

    Science.gov (United States)

    Yuk, Jae-Min; Kim, Tae Sung; Kim, Soo Yeon; Lee, Hye-Mi; Han, Jeongsu; Dufour, Catherine Rosa; Kim, Jin Kyung; Jin, Hyo Sun; Yang, Chul-Su; Park, Ki-Sun; Lee, Chul-Ho; Kim, Jin-Man; Kweon, Gi Ryang; Choi, Hueng-Sik; Vanacker, Jean-Marc; Moore, David D; Giguère, Vincent; Jo, Eun-Kyeong

    2015-07-21

    The orphan nuclear receptor estrogen-related receptor α (ERRα; NR3B1) is a key metabolic regulator, but its function in regulating inflammation remains largely unknown. Here, we demonstrate that ERRα negatively regulates Toll-like receptor (TLR)-induced inflammation by promoting Tnfaip3 transcription and fine-tuning of metabolic reprogramming in macrophages. ERRα-deficient (Esrra(-/-)) mice showed increased susceptibility to endotoxin-induced septic shock, leading to more severe pro-inflammatory responses than control mice. ERRα regulated macrophage inflammatory responses by directly binding the promoter region of Tnfaip3, a deubiquitinating enzyme in TLR signaling. In addition, Esrra(-/-) macrophages showed an increased glycolysis, but impaired mitochondrial respiratory function and biogenesis. Further, ERRα was required for the regulation of NF-κB signaling by controlling p65 acetylation via maintenance of NAD(+) levels and sirtuin 1 activation. These findings unravel a previously unappreciated role for ERRα as a negative regulator of TLR-induced inflammatory responses through inducing Tnfaip3 transcription and controlling the metabolic reprogramming. Copyright © 2015 Elsevier Inc. All rights reserved.

  20. Fear of Hypoglycemia, Parenting Stress, and Metabolic Control for Children with Type 1 Diabetes and Their Parents.

    Science.gov (United States)

    Viaene, Ann-Sofie; Van Daele, Tom; Bleys, Dries; Faust, Kelly; Massa, Guy G

    2017-03-01

    This study sets out to extend current knowledge of parenting stress and fear of hypoglycemia (FoH) in parents of children with type 1 diabetes mellitus (T1DM). We examined if the relationship between parental and children's FoH and metabolic control, as reflected by HbA1c, is mediated by parenting stress. A total of 63 parents and children with T1DM were recruited during their routine physician's appointment. Parents completed questionnaires on parenting stress and FoH. Children eight years and older also completed a questionnaire on FoH. HbA1c values were obtained from all children. Mediation analysis revealed an indirect association between parental FoH and HbA1c values through parenting stress (Sobel's z = 2.42, p = .02), but no indirect association between children's FoH and HbA1c. We concluded that parental FOH has an indirect association with the child's metabolic control that is mediated by parenting stress. More simply, fear of hypoglycemia predicts parent stress, which in turn, predicts metabolic control.

  1. Effect of strict metabolic control on regulation of subcutaneous blood flow in insulin-dependent diabetic patients

    DEFF Research Database (Denmark)

    Kastrup, J; Mathiesen, E R; Saurbrey, Nina

    1987-01-01

    washout technique. Mean arterial blood pressure was reduced by a maximum of 23 mmHg by elevating the limb above heart level and elevated to a maximum of 65 mmHg by head-up tilt; in the latter position venous pressure was kept constantly low by activation of the leg muscle vein pump (heel raising......The effect of 10 weeks of improved metabolic control on the impaired autoregulation of the subcutaneous blood flow was studied at the level of the lateral malleolus in eight long-term insulin-dependent diabetic patients with clinical microangiopathy. Blood flow was measured by the local 133-Xenon......). Improved metabolic control was achieved using either continuous subcutaneous insulin infusion or multiple insulin injections. The blood glucose concentration declined from (median) 12.7 to 6.8 mmol/l and the HbA1C level from 10.1 to 7.5% during strict metabolic control (p less than 0.01 and p less than 0...

  2. Impact of the level of metabolic control on the non-surgical periodontal therapy outcomes in diabetes mellitus type 2 patients: Clinical effects

    Directory of Open Access Journals (Sweden)

    Mirnić Jelena

    2013-01-01

    Full Text Available Introduction. Diabetes mellitus as a complex metabolic disease influences functioning of numerous organs. Chronic periodontitis is one of frequent diabetic complications. Objective. The aim of this study was to compare the clinical effects of non­surgical periodontal therapy between diabetes mellitus type 2 patients (DM type 2 and non­diabetic individuals (control group. Methods. Our study included 41 DM type 2 subjects and 21 non­diabetic individuals, all of them with chronic periodontitis. The diabetic group was divided into two subgroups based on the level of glycosylated hemoglobin (HbA1c as follows: D1 - 18 subjects with good metabolic control (HbA1c<7%, and D2 - 23 subjects with poor metabolic (HbA1c≥7%. State of oral hygiene and periodontal clinical parameters of subjects, such as: plaque index (PI, gingival index (GI, papilla bleeding index (PBI, probing pocket depth (PPD and clinical attachment level (CAL, were evaluated at the baseline and 3 months after scaling and root­planning. Results. ANOVA test showed that there was no statistically significant difference of treatment success between studied groups in relation to GI (p=0.52, PBI (p=0.36 and CAL (p=0.11. Reduction of PI and PPD in the control group (ΔPI=0.84; ΔPPD=0.35 mm was significantly higher (p<0.05 than the reduction of PI and PPD in patients with the diabetes (group D1 ΔPI=0.60, ΔPPD=0.11 mm; group D2 ΔPI=0.53, ΔPPD=0.11 mm. Conclusion. Although there were differences in treatment success between DM subjects and non­diabetic individuals, they were not significant for the most measured parameters. The results of this study did not absolutely support the assumption that the level of glycemic control significantly affected the periodontal therapy outcome in diabetics. [Projekat Ministarstva nauke Republike Srbije, br. 175075

  3. mTOR regulates metabolic adaptation of APCs in the lung and controls the outcome of allergic inflammation.

    Science.gov (United States)

    Sinclair, Charles; Bommakanti, Gayathri; Gardinassi, Luiz; Loebbermann, Jens; Johnson, Matthew Joseph; Hakimpour, Paul; Hagan, Thomas; Benitez, Lydia; Todor, Andrei; Machiah, Deepa; Oriss, Timothy; Ray, Anuradha; Bosinger, Steven; Ravindran, Rajesh; Li, Shuzhao; Pulendran, Bali

    2017-09-08

    Antigen-presenting cells (APCs) occupy diverse anatomical tissues, but their tissue-restricted homeostasis remains poorly understood. Here, working with mouse models of inflammation, we found that mechanistic target of rapamycin (mTOR)-dependent metabolic adaptation was required at discrete locations. mTOR was dispensable for dendritic cell (DC) homeostasis in secondary lymphoid tissues but necessary to regulate cellular metabolism and accumulation of CD103 + DCs and alveolar macrophages in lung. Moreover, while numbers of mTOR-deficient lung CD11b + DCs were not changed, they were metabolically reprogrammed to skew allergic inflammation from eosinophilic T helper cell 2 (T H 2) to neutrophilic T H 17 polarity. The mechanism for this change was independent of translational control but dependent on inflammatory DCs, which produced interleukin-23 and increased fatty acid oxidation. mTOR therefore mediates metabolic adaptation of APCs in distinct tissues, influencing the immunological character of allergic inflammation. Copyright © 2017 The Authors, some rights reserved; exclusive licensee American Association for the Advancement of Science. No claim to original U.S. Government Works.

  4. The role of tryptophan 2,3-dioxygenase in the hormonal control of tryptophan metabolism in isolated rat liver cells. Effects of glucocorticoids and experimental diabetes.

    OpenAIRE

    Salter, M; Pogson, C I

    1985-01-01

    The metabolism of L-tryptophan by isolated liver cells prepared from control, adrenalectomized, glucocorticoid-treated, acute-diabetic, chronic-diabetic and insulin-treated chronic-diabetic rats was studied. Liver cells from adrenalectomized rats metabolized tryptophan at rates comparable with the minimum diurnal rates of controls, but different from rates determined for cells from control rats 4h later. Administration of dexamethasone phosphate increased the activity of tryptophan 2,3-dioxyg...

  5. [Metabolic control and school performance in children with type 1 diabetes].

    Science.gov (United States)

    Román, Rossana; Garrido, Víctor; Novoa, Valentina; Mundaca, Gabriela; Pichuante, Ema; Rivera, Álvaro; Torres, Alberto; Fuentes, Margarita; Fuentes, Alison; Linares, Jeannette

    2017-01-01

    The impact of type 1 diabetes (T1D) on school performance is controversial. To study the relationship between school performance and metabolic control in children with T1D (Ch-T1D), comparing their school grades to general population children (Ch-GP). Clinical data for 66 Ch-T1D was reviewed, school grades were compared in Ch-T1D with Glycated Haemoglobin (HbA1c) HbA1c < 7.5% and ≥ 7.5%. School marks were also compared between Ch-T1D and Ch-GP from the same level, community and school type (public, private o chartered). Simple linear regression analysis and Mann Whitney test were used to compare groups. A p < 0.05 was considered significant. Ch-T1D were: 13.4 ± 2.9 years old, T1D duration: 5.3 ± 3.2 years, HbA1c was 8.6 ± 1.9% and capillary blood glucose was measured 3.2 ± 1.2 times per day. Grade averages showed no correlation with HbA1c, diabetes duration, hypothyroidism, mental health issues, neither with hypoglycemia or ketoacidosis records. However, primary education Ch-T1D showed lower grades than Ch-GP 5.6 ± 0.7 and 6.0 ± 0.2 (p = 0,0002). School grades correlated with the number of capillary blood glucose readings per day, Pearson correlation coefficient (r) 0.25, 0.41, 0.52 and 0.58 with general grade point average, math, language, and history average respectively (p < 0.05). School non-pass rate was 6.1% in Ch-T1D and 4.8% in Ch-GP (p = 0.65) and school dropout rate was 10.5% in Ch-T1D and 7.7% in Ch-GP (p = 0.47). Ch-T1D attending primary school showed lower school grades than Ch-GP, and patients who more frequently checked capillary blood glucose showed better school grades. T1D may have a deleterious impact on school performance.

  6. Very low calorie diet without aspartame in obese subjects: improved metabolic control after 4 weeks treatment.

    Science.gov (United States)

    Norén, Erik; Forssell, Henrik

    2014-07-28

    Very low calorie diet (VLCD) is routinely used in programs for treatment of obesity and before bariatric surgery in order to reduce risk of postoperative complications. Aspartame, an artificial sweetener, is commonly used in VLCD and is well approved as a food additive without any adverse effects. The development of a new fructose containing VLCD formula without aspartame raises questions as to effects on glucose and lipid control. As part of an ongoing study of a novel bariatric surgery procedure, twenty-five obese subjects with mean body mass index (BMI) 39.8 kg/m2 and mean age of 48.8 years enrolled in a single center observational study. Seven subjects presented with type 2 diabetes mellitus. The subjects underwent four weeks dietary treatment with VLCD Slanka (Slanka). Blood samples including fasting plasma glucose, HbA1c, cholesterol and triglycerides were performed at start and after four weeks of diet. Blood pressure and weight were noted. All subjects completed the diet without any adverse events. Mean weight reduction was 8.2 kg with 95% confidence interval 7.1-9.2 kg (p = 0.001). Excess weight (i.e. proportion of weight exceeding BMI 25) loss decreased by median 19.5% (inter quartile range (IQR) 16,8-24,2). Median fasting plasma glucose was at inclusion 5,6 mmol/l (IQR 5,3-6,8) and after diet 4.8 mmol/l (IQR 4,6-5,2) (p = 0.001). Median HbA1c changed from 39 mmol/mol (IQR 37-44) to 37 mmol/mol (IQR 35-43) (p = 0.001). There was also significant reduction in cholesterol and triglyceride levels as well as in systolic blood pressure. Changes in other monitored blood chemistry values were without clinical importance. Four weeks treatment with fructose containing VLCD of obese subjects preparing for bariatric surgery gave a substantial weight reduction without any significant negative metabolic effects.

  7. Does the Good Schools Toolkit Reduce Physical, Sexual and Emotional Violence, and Injuries, in Girls and Boys equally? A Cluster-Randomised Controlled Trial.

    Science.gov (United States)

    Devries, Karen M; Knight, Louise; Allen, Elizabeth; Parkes, Jenny; Kyegombe, Nambusi; Naker, Dipak

    2017-10-01

    We aimed to investigate whether the Good School Toolkit reduced emotional violence, severe physical violence, sexual violence and injuries from school staff to students, as well as emotional, physical and sexual violence between peers, in Ugandan primary schools. We performed a two-arm cluster randomised controlled trial with parallel assignment. Forty-two schools in one district were allocated to intervention (n = 21) or wait-list control (n = 21) arms in 2012. We did cross-sectional baseline and endline surveys in 2012 and 2014, and the Good School Toolkit intervention was implemented for 18 months between surveys. Analyses were by intention to treat and are adjusted for clustering within schools and for baseline school-level proportions of outcomes. The Toolkit was associated with an overall reduction in any form of violence from staff and/or peers in the past week towards both male (aOR = 0.34, 95%CI 0.22-0.53) and female students (aOR = 0.55, 95%CI 0.36-0.84). Injuries as a result of violence from school staff were also lower in male (aOR = 0.36, 95%CI 0.20-0.65) and female students (aOR = 0.51, 95%CI 0.29-0.90). Although the Toolkit seems to be effective at reducing violence in both sexes, there is some suggestion that the Toolkit may have stronger effects in boys than girls. The Toolkit is a promising intervention to reduce a wide range of different forms of violence from school staff and between peers in schools, and should be urgently considered for scale-up. Further research is needed to investigate how the intervention could engage more successfully with girls.

  8. Fatty liver associated with metabolic derangement in patients with chronic kidney disease: A controlled attenuation parameter study

    Directory of Open Access Journals (Sweden)

    Chang-Yun Yoon

    2017-03-01

    Full Text Available Background: Hepatic steatosis measured with controlled attenuation parameter (CAP using transient elastography predicts metabolic syndrome in the general population. We investigated whether CAP predicted metabolic syndrome in chronic kidney disease patients. Methods: CAP was measured with transient elastography in 465 predialysis chronic kidney disease patients (mean age, 57.5 years. Results: The median CAP value was 239 (202–274 dB/m. In 195 (41.9% patients with metabolic syndrome, diabetes mellitus was more prevalent (105 [53.8%] vs. 71 [26.3%], P < 0.001, with significantly increased urine albumin-to-creatinine ratio (184 [38–706] vs. 56 [16–408] mg/g Cr, P = 0.003, high sensitivity C-reactive protein levels (5.4 [1.4–28.2] vs. 1.7 [0.6–9.9] mg/L, P < 0.001, and CAP (248 [210–302] vs. 226 [196–259] dB/m, P < 0.001. In multiple linear regression analysis, CAP was independently related to body mass index (β = 0.742, P < 0.001, triglyceride levels (β = 2.034, P < 0.001, estimated glomerular filtration rate (β = 0.316, P = 0.001, serum albumin (β = 1.386, P < 0.001, alanine aminotransferase (β = 0.064, P = 0.029, and total bilirubin (β = −0.881, P = 0.009. In multiple logistic regression analysis, increased CAP was independently associated with increased metabolic syndrome risk (per 10 dB/m increase; odds ratio, 1.093; 95% confidence interval, 1.009–1.183; P = 0.029 even after adjusting for multiple confounding factors. Conclusion: Increased CAP measured with transient elastography significantly correlated with and could predict increased metabolic syndrome risk in chronic kidney disease patients.

  9. A circadian rhythm orchestrated by histone deacetylase 3 controls hepatic lipid metabolism

    DEFF Research Database (Denmark)

    Feng, Dan; Liu, Tao; Sun, Zheng

    2011-01-01

    Disruption of the circadian clock exacerbates metabolic diseases, including obesity and diabetes. We show that histone deacetylase 3 (HDAC3) recruitment to the genome displays a circadian rhythm in mouse liver. Histone acetylation is inversely related to HDAC3 binding, and this rhythm is lost whe...

  10. The Secret Life of NAD(+): An Old Metabolite Controlling New Metabolic Signaling Pathways

    NARCIS (Netherlands)

    Houtkooper, Riekelt H.; Cantó, Carles; Wanders, Ronald J.; Auwerx, Johan

    2010-01-01

    A century after the identification of a coenzymatic activity for NAD(+), NAD(+) metabolism has come into the spotlight again due to the potential therapeutic relevance of a set of enzymes whose activity is tightly regulated by the balance between the oxidized and reduced forms of this metabolite. In

  11. Carbon catabolite repression and global control of the carbohydrate metabolism in Lactococcus lactis

    NARCIS (Netherlands)

    Luesink, E.J.

    1998-01-01

    In view of the economic importance of fermented dairy products considerable scientific attention has been given to various steps of fermentation processes, including the L-lactate formation of lactic acid bacteria (de Vos, 1996). In particular, the carbohydrate metabolism of L. lactis has

  12. A Major Role for Perifornical Orexin Neurons in the Control of Glucose Metabolism in Rats

    NARCIS (Netherlands)

    Yi, Chun-Xia; Serlie, Mireille J.; Ackermans, Mariette T.; Foppen, Ewout; Buijs, Ruud M.; Sauerwein, Hans P.; Fliers, Eric; Kalsbeek, Andries

    2009-01-01

    OBJECTIVE-The hypothalamic neuropeptide orexin influences (feeding) behavior as well as energy metabolism. Administration of exogenous orexin-A into the brain has been shown to increase both food intake and blood glucose levels. In the present study, we investigated the role of endogenous

  13. A randomized controlled trial: branched-chain amino acid levels and glucose metabolism in patients with obesity and sleep apnea.

    Science.gov (United States)

    Barceló, Antonia; Morell-Garcia, Daniel; Salord, Neus; Esquinas, Cristina; Pérez, Gerardo; Pérez, Antonio; Monasterio, Carmen; Gasa, Merce; Fortuna, Ana Maria; Montserrat, Josep Maria; Mayos, Mercedes

    2017-12-01

    There is evidence that changes in branched-chain amino acid (BCAA) levels may correlate with the efficacy of therapeutic interventions for affecting improvement in metabolic control. The objective of this study was to evaluate whether serum concentrations of BCAAs (leucine, isoleucine, valine) could mediate in insulin sensitivity and glucose tolerance after continuous positive airway pressure (CPAP) treatment in patients with obstructive sleep apnea (OSA). A prospective randomized controlled trial of OSA patients with morbid obesity was conducted. Eighty patients were randomized into two groups: 38 received conservative treatment and 42 received CPAP treatment for 12 weeks. Plasma levels of BCAA, glucose tolerance and insulin resistance were evaluated at baseline and after treatment. After treatment, significant decreases of leucine levels were observed in both groups when compared with baseline levels (P fasting plasma glucose and glycosylated haemoglobin values only in the conservative group (P < 0.05). In summary, we found that the treatment with CPAP for 12 weeks caused similar changes in circulating BCAAs concentrations to conservative treatment and a differential metabolic response of CPAP and conservative treatment was observed between the relationship of BCAAs and glucose homeostasis. Additional studies are needed to determine the interplay between branched-chain amino acids and glucose metabolism in patients with sleep apnea. © 2017 European Sleep Research Society.

  14. Association between Two Resistin Gene Polymorphisms and Metabolic Syndrome in Jilin, Northeast China: A Case-Control Study

    Directory of Open Access Journals (Sweden)

    Yingli Fu

    2017-01-01

    Full Text Available Metabolic syndrome (MetS is a significant health care problem worldwide and is characterized by increased fasting glucose and obesity. Resistin is a protein hormone produced both by adipocytes and immunocompetent cells, including those residing in adipose tissue, and is believed to modulate glucose tolerance and insulin action. This study examined the association of resistin gene polymorphisms, rs1862513 and rs3745368, and related haplotypes with the development of metabolic syndrome in a Han Chinese population. This case-control study was performed on 3792 subjects, including 1771 MetS cases and 2021 healthy controls from the Jilin province of China. Metabolic syndrome was defined according to the criteria of the International Diabetes Federation (IDF. Logistic regression analysis was used to estimate the relationship between gene polymorphism and MetS. Our results showed that there were no significant associations between MetS and the genotype distributions in four kinds of inheritance models, allele frequencies, and related haplotypes of resistin gene polymorphisms rs1862513 and rs3745368 (all p values > 0.05. Based on our study findings, we concluded that mutations in resistin genes are not associated with the presence of MetS in a Han Chinese population from Jilin province in China.

  15. Programming Post-Translational Control over the Metabolic Labeling of Cellular Proteins with a Noncanonical Amino Acid.

    Science.gov (United States)

    Thomas, Emily E; Pandey, Naresh; Knudsen, Sarah; Ball, Zachary T; Silberg, Jonathan J

    2017-08-18

    Transcriptional control can be used to program cells to label proteins with noncanonical amino acids by regulating the expression of orthogonal aminoacyl tRNA synthetases (aaRSs). However, we cannot yet program cells to control labeling in response to aaRS and ligand binding. To identify aaRSs whose activities can be regulated by interactions with ligands, we used a combinatorial approach to discover fragmented variants of Escherichia coli methionyl tRNA synthetase (MetRS) that require fusion to associating proteins for maximal activity. We found that these split proteins could be leveraged to create ligand-dependent MetRS using two approaches. When a pair of MetRS fragments was fused to FKBP12 and the FKBP-rapamycin binding domain (FRB) of mTOR and mutations were introduced that direct substrate specificity toward azidonorleucine (Anl), Anl metabolic labeling was significantly enhanced in growth medium containing rapamycin, which stabilizes the FKBP12-FRB complex. In addition, fusion of MetRS fragments to the termini of the ligand-binding domain of the estrogen receptor yielded proteins whose Anl metabolic labeling was significantly enhanced when 4-hydroxytamoxifen (4-HT) was added to the growth medium. These findings suggest that split MetRS can be fused to a range of ligand-binding proteins to create aaRSs whose metabolic labeling activities depend upon post-translational interactions with ligands.

  16. A double blind, placebo-controlled, randomized crossover study of the acute metabolic effects of olanzapine in healthy volunteers.

    Directory of Open Access Journals (Sweden)

    Vance L Albaugh

    Full Text Available Atypical antipsychotics exhibit metabolic side effects including diabetes mellitus and obesity. The adverse events are preceded by acute worsening of oral glucose tolerance (oGTT along with reduced plasma free fatty acids (FFA and leptin in animal models. It is unclear whether the same acute effects occur in humans.A double blind, randomized, placebo-controlled crossover trial was conducted to examine the potential metabolic effects of olanzapine in healthy volunteers. Participants included male (8 and female (7 subjects [18-30 years old, BMI 18.5-25]. Subjects received placebo or olanzapine (10 mg/day for three days prior to oGTT testing. Primary endpoints included measurement of plasma leptin, oral glucose tolerance, and plasma free fatty acids (FFA. Secondary metabolic endpoints included: triglycerides, total cholesterol, high- and low-density lipoprotein cholesterol, heart rate, blood pressure, body weight and BMI. Olanzapine increased glucose Area Under the Curve (AUC by 42% (2808±474 vs. 3984±444 mg/dl·min; P = 0.0105 during an oGTT. Fasting plasma leptin and triglycerides were elevated 24% (Leptin: 6.8±1.3 vs. 8.4±1.7 ng/ml; P = 0.0203 and 22% (Triglycerides: 88.9±10.1 vs. 108.2±11.6 mg/dl; P = 0.0170, whereas FFA and HDL declined by 32% (FFA: 0.38±0.06 vs. 0.26±0.04 mM; P = 0.0166 and 11% (54.2±4.7 vs. 48.9±4.3 mg/dl; P = 0.0184, respectively after olanzapine. Other measures were unchanged.Olanzapine exerts some but not all of the early endocrine/metabolic changes observed in rodent models of the metabolic side effects, and this suggest that antipsychotic effects are not limited to perturbations in glucose metabolism alone. Future prospective clinical studies should focus on identifying which reliable metabolic alterations might be useful as potential screening tools in assessing patient susceptibility to weight gain and diabetes caused by atypical antipsychotics.ClinicalTrials.gov NCT00741026.

  17. Attenuation of insulin-evoked responses in brain networks controlling appetite and reward in insulin resistance: the cerebral basis for impaired control of food intake in metabolic syndrome?

    Science.gov (United States)

    Anthony, Karen; Reed, Laurence J; Dunn, Joel T; Bingham, Emma; Hopkins, David; Marsden, Paul K; Amiel, Stephanie A

    2006-11-01

    The rising prevalence of obesity and type 2 diabetes is a global challenge. A possible mechanism linking insulin resistance and weight gain would be attenuation of insulin-evoked responses in brain areas relevant to eating in systemic insulin resistance. We measured brain glucose metabolism, using [(18)F]fluorodeoxyglucose positron emission tomography, in seven insulin-sensitive (homeostasis model assessment of insulin resistance [HOMA-IR] = 1.3) and seven insulin-resistant (HOMA-IR = 6.3) men, during suppression of endogenous insulin by somatostatin, with and without an insulin infusion that elevated insulin to 24.6 +/- 5.2 and 23.2 +/- 5.8 mU/l (P = 0.76), concentrations similar to fasting levels of the resistant subjects and approximately threefold above those of the insulin-sensitive subjects. Insulin-evoked change in global cerebral metabolic rate for glucose was reduced in insulin resistance (+7 vs. +17.4%, P = 0.033). Insulin was associated with increased metabolism in ventral striatum and prefrontal cortex and with decreased metabolism in right amygdala/hippocampus and cerebellar vermis (P reward. Diminishing the link be-tween control of food intake and energy balance may contribute to development of obesity in insulin resistance.

  18. The Antioxidant Cofactor Alpha-Lipoic Acid May Control Endogenous Formaldehyde Metabolism in Mammals

    Directory of Open Access Journals (Sweden)

    Anastasia V. Shindyapina

    2017-12-01

    Full Text Available The healthy human body contains small amounts of metabolic formaldehyde (FA that mainly results from methanol oxidation by pectin methylesterase, which is active in a vegetable diet and in the gastrointestinal microbiome. With age, the ability to maintain a low level of FA decreases, which increases the risk of Alzheimer's disease and dementia. It has been shown that 1,2-dithiolane-3-pentanoic acid or alpha lipoic acid (ALA, a naturally occurring dithiol and antioxidant cofactor of mitochondrial α-ketoacid dehydrogenases, increases glutathione (GSH content and FA metabolism by mitochondrial aldehyde dehydrogenase 2 (ALDH2 thus manifests a therapeutic potential beyond its antioxidant property. We suggested that ALA can contribute to a decrease in the FA content of mammals by acting on ALDH2 expression. To test this assumption, we administered ALA in mice in order to examine the effect on FA metabolism and collected blood samples for the measurement of FA. Our data revealed that ALA efficiently eliminated FA in mice. Without affecting the specific activity of FA-metabolizing enzymes (ADH1, ALDH2, and ADH5, ALA increased the GSH content in the brain and up-regulated the expression of the FA-metabolizing ALDH2 gene in the brain, particularly in the hippocampus, but did not impact its expression in the liver in vivo or in rat liver isolated from the rest of the body. After ALA administration in mice and in accordance with the increased content of brain ALDH2 mRNA, we detected increased ALDH2 activity in brain homogenates. We hypothesized that the beneficial effects of ALA on patients with Alzheimer's disease may be associated with accelerated ALDH2-mediated FA detoxification and clearance.

  19. Euglena in time: Evolution, control of central metabolic processes and multi-domain proteins in carbohydrate and natural product biochemistry

    Directory of Open Access Journals (Sweden)

    Ellis C. O’Neill

    2015-12-01

    Full Text Available Euglena gracilis is a eukaryotic microalgae that has been the subject of scientific study for hundreds of years. It has a complex evolutionary history, with traces of at least four endosymbiotic genomes and extensive horizontal gene transfer. Given the importance of Euglena in terms of evolutionary cell biology and its unique taxonomic position, we initiated a de novo transcriptome sequencing project in order to understand this intriguing organism. By analysing the proteins encoded in this transcriptome, we can identify an extremely complex metabolic capacity, rivalling that of multicellular organisms. Many genes have been acquired from what are now very distantly related species. Herein we consider the biology of Euglena in different time frames, from evolution through control of cell biology to metabolic processes associated with carbohydrate and natural products biochemistry.

  20. Metabolic Control in Mammalian Fed-Batch Cell Cultures for Reduced Lactic Acid Accumulation and Improved Process Robustness

    Directory of Open Access Journals (Sweden)

    Viktor Konakovsky

    2016-01-01

    Full Text Available Biomass and cell-specific metabolic rates usually change dynamically over time, making the “feed according to need” strategy difficult to realize in a commercial fed-batch process. We here demonstrate a novel feeding strategy which is designed to hold a particular metabolic state in a fed-batch process by adaptive feeding in real time. The feed rate is calculated with a transferable biomass model based on capacitance, which changes the nutrient flow stoichiometrically in real time. A limited glucose environment was used to confine the cell in a particular metabolic state. In order to cope with uncertainty, two strategies were tested to change the adaptive feed rate and prevent starvation while in limitation: (i inline pH and online glucose concentration measurement or (ii inline pH alone, which was shown to be sufficient for the problem statement. In this contribution, we achieved metabolic control within a defined target range. The direct benefit was two-fold: the lactic acid profile was improved and pH could be kept stable. Multivariate Data Analysis (MVDA has shown that pH influenced lactic acid production or consumption in historical data sets. We demonstrate that a low pH (around 6.8 is not required for our strategy, as glucose availability is already limiting the flux. On the contrary, we boosted glycolytic flux in glucose limitation by setting the pH to 7.4. This new approach led to a yield of lactic acid/glucose (Y L/G around zero for the whole process time and high titers in our labs. We hypothesize that a higher carbon flux, resulting from a higher pH, may lead to more cells which produce more product. The relevance of this work aims at feeding mammalian cell cultures safely in limitation with a desired metabolic flux range. This resulted in extremely stable, low glucose levels, very robust pH profiles without acid/base interventions and a metabolic state in which lactic acid was consumed instead of being produced from day 1. With

  1. Individual differences in arsenic metabolism and lung cancer in a case-control study in Cordoba, Argentina

    International Nuclear Information System (INIS)

    Steinmaus, Craig; Yuan Yan; Kalman, Dave; Rey, Omar A.; Skibola, Christine F.; Dauphine, Dave; Basu, Anamika; Porter, Kristin E.; Hubbard, Alan; Bates, Michael N.; Smith, Martyn T.; Smith, Allan H.

    2010-01-01

    In humans, ingested inorganic arsenic is metabolized to monomethylarsenic (MMA) then to dimethylarsenic (DMA), although in most people this process is not complete. Previous studies have identified associations between the proportion of urinary MMA (%MMA) and increased risks of several arsenic-related diseases, although none of these reported on lung cancer. In this study, urinary arsenic metabolites were assessed in 45 lung cancer cases and 75 controls from arsenic-exposed areas in Cordoba, Argentina. Folate has also been linked to arsenic-disease susceptibility, thus an exploratory assessment of associations between single nucleotide polymorphisms in folate metabolizing genes, arsenic methylation, and lung cancer was also conducted. In analyses limited to subjects with metabolite concentrations above detection limits, the mean %MMA was higher in cases than in controls (17.5% versus 14.3%, p = 0.01). The lung cancer odds ratio for subjects with %MMA in the upper tertile compared to those in the lowest tertile was 3.09 (95% CI, 1.08-8.81). Although the study size was too small for a definitive conclusion, there was an indication that lung cancer risks might be highest in those with a high %MMA who also carried cystathionine β-synthase (CBS) rs234709 and rs4920037 variant alleles. This study is the first to report an association between individual differences in arsenic metabolism and lung cancer, a leading cause of arsenic-related mortality. These results add to the increasing body of evidence that variation in arsenic metabolism plays an important role in arsenic-disease susceptibility.

  2. A real-time control system of gene expression using ligand-bound nucleic acid aptamer for metabolic engineering.

    Science.gov (United States)

    Wang, Jing; Cui, Xun; Yang, Le; Zhang, Zhe; Lv, Liping; Wang, Haoyuan; Zhao, Zhenmin; Guan, Ningzi; Dong, Lichun; Chen, Rachel

    2017-07-01

    Artificial control of bio-functions through regulating gene expression is one of the most important and attractive technologies to build novel living systems that are useful in the areas of chemical synthesis, nanotechnology, pharmacology, cell biology. Here, we present a novel real-time control system of gene regulation that includes an enhancement element by introducing duplex DNA aptamers upstream promoter and a repression element by introducing a RNA aptamer upstream ribosome binding site. With the presence of ligands corresponding to the DNA aptamers, the expression of the target gene can be potentially enhanced at the transcriptional level by strengthening the recognition capability of RNAP to the recognition region and speeding up the separation efficiency of the unwinding region due to the induced DNA bubble around the thrombin-bound aptamers; while with the presence of RNA aptamer ligand, the gene expression can be repressed at the translational level by weakening the recognition capability of ribosome to RBS due to the shielding of RBS by the formed aptamer-ligand complex upstream RBS. The effectiveness and potential utility of the developed gene regulation system were demonstrated by regulating the expression of ecaA gene in the cell-free systems. The realistic metabolic engineering application of the system has also tested by regulating the expression of mgtC gene and thrombin cDNA in Escherichia coli JD1021 for controlling metabolic flux and improving thrombin production, verifying that the real-time control system of gene regulation is able to realize the dynamic regulation of gene expression with potential applications in bacterial physiology studies and metabolic engineering. Copyright © 2017. Published by Elsevier Inc.

  3. The efficiency of telemedicine to optimize metabolic control in patients with type 1 diabetes mellitus: Telemed study.

    Science.gov (United States)

    Esmatjes, Enric; Jansà, Margarida; Roca, Daria; Pérez-Ferre, Natalia; del Valle, Laura; Martínez-Hervás, Sergio; Ruiz de Adana, Marisol; Linares, Francisca; Batanero, Ricardo; Vázquez, Federico; Gomis, Ramon; de Solà-Morales, Oriol

    2014-07-01

    This study evaluated the impact of an Internet-based telematic system on the economic and clinical management of patients with type 1 diabetes mellitus. This 6-month prospective, randomized, comparative, open, multicenter study included patients with type 1 diabetes >18 years old treated with multiple insulin doses and with a glycated hemoglobin (HbA1c) level of >8%. We compared an intervention group (IG) (two face-to-face and five telematic appointments) with a control group (CG) (seven face-to-face appointments). The variables studied were (1) patient and healthcare team costs, (2) metabolic control, (3) knowledge of diabetes, (4) quality of life, and (5) self-care treatment adherence. Of the 154 patients included, 118 (76.6%) completed the study (IG, 54; CG, 64). The time used by the CG to follow the program was 823±645 min versus 353±222 min in the IG (Pknowledge and self-care treatment adherence. The use of interactive telematic appointments in subjects with type 1 diabetes and inadequate metabolic control is an efficient strategy, providing results comparable to those of face-to-face appointments in relation to improvement in glycemic control, knowledge acquisition, and self-care treatment adherence, with a significant reduction in the time used, especially by patients.

  4. [Metabolic myopathies].

    Science.gov (United States)

    Papazian, Óscar; Rivas-Chacón, Rafael

    2013-09-06

    To review the metabolic myopathies manifested only by crisis of myalgias, cramps and rigidity of the muscles with decreased voluntary contractions and normal inter crisis neurologic examination in children and adolescents. These metabolic myopathies are autosomic recessive inherited enzymatic deficiencies of the carbohydrates and lipids metabolisms. The end result is a reduction of intra muscle adenosine triphosphate, mainly through mitochondrial oxidative phosphorylation, with decrease of available energy for muscle contraction. The one secondary to carbohydrates intra muscle metabolism disorders are triggered by high intensity brief (fatty acids metabolism disorders are triggered by low intensity prolonged (> 10 min) exercises. The conditions in the first group in order of decreasing frequency are the deficiencies of myophosforilase (GSD V), muscle phosphofructokinase (GSD VII), phosphoglycerate mutase 1 (GSD X) and beta enolase (GSD XIII). The conditions in the second group in order of decreasing frequency are the deficiencies of carnitine palmitoyl transferase II and very long chain acyl CoA dehydrogenase. The differential characteristics of patients in each group and within each group will allow to make the initial presumptive clinical diagnosis in the majority and then to order only the necessary tests to achieve the final diagnosis. Treatment during the crisis includes hydration, glucose and alkalinization of urine if myoglobin in blood and urine are elevated. Prevention includes avoiding exercise which may induce the crisis and fasting. The prognosis is good with the exception of rare cases of acute renal failure due to hipermyoglobinemia because of severe rabdomyolisis.

  5. Tbx15 controls skeletal muscle fibre-type determination and muscle metabolism

    Science.gov (United States)

    Lee, Kevin Y.; Singh, Manvendra K.; Ussar, Siegfried; Wetzel, Petra; Hirshman, Michael F.; Goodyear, Laurie J.; Kispert, Andreas; Kahn, C. Ronald

    2015-01-01

    Skeletal muscle is composed of both slow-twitch oxidative myofibers and fast-twitch glycolytic myofibers that differentially impact muscle metabolism, function and eventually whole-body physiology. Here we show that the mesodermal transcription factor T-box 15 (Tbx15) is highly and specifically expressed in glycolytic myofibers. Ablation of Tbx15 in vivo leads to a decrease in muscle size due to a decrease in the number of glycolytic fibres, associated with a small increase in the number of oxidative fibres. This shift in fibre composition results in muscles with slower myofiber contraction and relaxation, and also decreases whole-body oxygen consumption, reduces spontaneous activity, increases adiposity and glucose intolerance. Mechanistically, ablation of Tbx15 leads to activation of AMPK signalling and a decrease in Igf2 expression. Thus, Tbx15 is one of a limited number of transcription factors to be identified with a critical role in regulating glycolytic fibre identity and muscle metabolism. PMID:26299309

  6. Control of overweight and obesity in childhood through education in meal time habits. The 'good manners for a healthy future' programme.

    Science.gov (United States)

    Salazar Vázquez, B Y; Salazar Vázquez, M A; López Gutiérrez, G; Acosta Rosales, K; Cabrales, P; Vadillo-Ortega, F; Intaglietta, M; Pérez Tamayo, R; Schmid-Schönbein, G W

    2016-12-01

    Our aim is to determine the effect of paced eating, exposure to an educational programme that promotes healthy eating habits and allowing the satiety reflex to limit food intake in controlling weight gain in healthy adolescents. Fifty-four healthy individuals consisting of 18 adolescent girls and 36 boys aged 12 ± 2 years were given recommendations for reducing eating rate without changing diet or meal size according to the educational programme 'good manners for a healthy future'. Each participant was provided with a 30-s portable hourglass to pace time between bites. Individuals using and not using the hourglass were placed either into an 'adhering' or a 'non-adhering' group, respectively. Control data were obtained from a similar population. Initially, the adhering group had higher weight compared with the non-adhering group (64.1 ± 13.2 vs. 56.2 ± 11.7 kg). Control group weight was no different from the study group at baseline (56.3 ± 10.3 kg). Weight in the adhering group decreased after the first semester of participation by 2.0 ± 5.7% and after a year by 3.4 ± 4.8%, while the non-adhering group gained weight by 5.8 ± 4.5% and 12.6 ± 8.3%. The control group increased weight after a year by 8.2 ± 6.5%. In total, 18 non-adhering and 14 adhering adolescents completed the study. This 1-year study shows a statistically significant association between rate of food intake and weight control in adherence to an educational programme directed at developing healthy eating habits. The proposed behavioural training may serve as an option for weight control in adolescents. © 2015 The Authors. Pediatric Obesity published by John Wiley & Sons Ltd on behalf of World Obesity Federation.

  7. Determining the control circuitry of redox metabolism at the genome-scale.

    Directory of Open Access Journals (Sweden)

    Stephen Federowicz

    2014-04-01

    Full Text Available Determining how facultative anaerobic organisms sense and direct cellular responses to electron acceptor availability has been a subject of intense study. However, even in the model organism Escherichia coli, established mechanisms only explain a small fraction of the hundreds of genes that are regulated during electron acceptor shifts. Here we propose a qualitative model that accounts for the full breadth of regulated genes by detailing how two global transcription factors (TFs, ArcA and Fnr of E. coli, sense key metabolic redox ratios and act on a genome-wide basis to regulate anabolic, catabolic, and energy generation pathways. We first fill gaps in our knowledge of this transcriptional regulatory network by carrying out ChIP-chip and gene expression experiments to identify 463 regulatory events. We then interfaced this reconstructed regulatory network with a highly curated genome-scale metabolic model to show that ArcA and Fnr regulate >80% of total metabolic flux and 96% of differential gene expression across fermentative and nitrate respiratory conditions. Based on the data, we propose a feedforward with feedback trim regulatory scheme, given the extensive repression of catabolic genes by ArcA and extensive activation of chemiosmotic genes by Fnr. We further corroborated this regulatory scheme by showing a 0.71 r(2 (p<1e-6 correlation between changes in metabolic flux and changes in regulatory activity across fermentative and nitrate respiratory conditions. Finally, we are able to relate the proposed model to a wealth of previously generated data by contextualizing the existing transcriptional regulatory network.

  8. Involvement of AMP-activated protein kinase in control of adipocyte metabolism during starvation

    Czech Academy of Sciences Publication Activity Database

    Kopecký, Jan; Šponarová, Jana; Mustard, K. J.; Flachs, Pavel; Horáková, Olga; Rossmeisl, Martin; Bardová, Kristina; Thomason-Hughes, M.; Braunerová, Radka; Hardie, D. G.

    2005-01-01

    Roč. 6, č. S1 (2005), s. 52-52 ISSN 1467-7881. [European Congress on Obesity /14./. 01.06.2005-04.06.2005, Athens] R&D Projects: GA MŠk(CZ) 1M0520; GA ČR GA303/05/2580 Institutional research plan: CEZ:AV0Z50110509 Keywords : AMPK * adipocyte * starvation * fatty acid oxidation Subject RIV: FB - Endocrinology, Diabetology, Metabolism, Nutrition

  9. The impact of electronic education on metabolic control indicators in patients with diabetes who need insulin: a randomised clinical control trial.

    Science.gov (United States)

    Moattari, Marzieh; Hashemi, Maryam; Dabbaghmanesh, Mohammad H

    2013-01-01

    To determine the impact of electronic education on metabolic control indicators in patients with diabetes who were insulin dependent. Education can play an important role in controlling diabetes. Electronic (web-based, telehealth) education may be an efficient way to improve the patients' ability to control this disease. Randomised clinical control study. The participants in this clinical study were 48 insulin-dependent patients referred to diabetes centres in Shiraz, Iran. Serum concentrations of haemoglobin A(1C) , fasting blood sugar, triglycerides and high-density and low-density lipoprotein cholesterol were measured. Then the participants were divided randomly into control and experimental groups (n = 24). Participants in the experimental group received a specially designed electronic education programme for twelve weeks. The main components of the programme were a consultation service, quick answers to patients' questions, contact with the healthcare team and educational materials. At the end of the intervention period, all serum values were measured again in both groups. The data were compared using spss v 13·5 software. Serum concentrations of haemoglobin A(1C) (p education programme was useful in lowering two metabolic indicators of diabetes. Electronic education can be associated with increased health and patient satisfaction, and can eliminate the need to train personnel. © 2012 Blackwell Publishing Ltd.

  10. Systematic Sensitivity Analysis of Metabolic Controllers During Reductions in Skeletal Muscle Blood Flow

    Science.gov (United States)

    Radhakrishnan, Krishnan; Cabrera, Marco

    2000-01-01

    An acute reduction in oxygen delivery to skeletal muscle is generally associated with profound derangements in substrate metabolism. Given the complexity of the human bioenergetic system and its components, it is difficult to quantify the interaction of cellular metabolic processes to maintain ATP homeostasis during stress (e.g., hypoxia, ischemia, and exercise). Of special interest is the determination of mechanisms relating tissue oxygenation to observed metabolic responses at the tissue, organ, and whole body levels and the quantification of how changes in oxygen availability affect the pathways of ATP synthesis and their regulation. In this study, we apply a previously developed mathematical model of human bioenergetics to study effects of ischemia during periods of increased ATP turnover (e.g., exercise). By using systematic sensitivity analysis the oxidative phosphorylation rate was found to be the most important rate parameter affecting lactate production during ischemia under resting conditions. Here we examine whether mild exercise under ischemic conditions alters the relative importance of pathways and parameters previously obtained.

  11. The Aging Clock and Circadian Control of Metabolism and Genome Stability

    Directory of Open Access Journals (Sweden)

    Victoria P. Belancio

    2015-01-01

    Full Text Available It is widely accepted that aging is characterized by a gradual decline in the efficiency and accuracy of biological processes, leading to deterioration of physiological functions and development of age-associated diseases. Age-dependent accumulation of genomic instability and development of metabolic syndrome are well-recognized components of the aging phenotype, both of which have been extensively studied. Existing findings strongly support the view that the integrity of the cellular genome and metabolic function can be influenced by light at night (LAN and associated suppression of circadian melatonin production. While LAN is reported to accelerate aging by promoting age-associated carcinogenesis in several animal models, the specific molecular mechanism(s of its action are not fully understood. Here, we review literature supporting a connection between LAN-induced central circadian disruption of peripheral circadian rhythms and clock function, LINE-1 retrotransposon-associated genomic instability, metabolic deregulation, and aging. We propose that aging is a progressive decline in the stability, continuity and synchronization of multi-frequency oscillations in biological processes to a temporally disorganized state. By extension, healthy aging is the ability to maintain the most consistent, stable and entrainable rhythmicity and coordination of these oscillations, at the molecular, cellular, and systemic levels.

  12. ATP-Citrate Lyase Controls a Glucose-to-Acetate Metabolic Switch

    Directory of Open Access Journals (Sweden)

    Steven Zhao

    2016-10-01

    Full Text Available Mechanisms of metabolic flexibility enable cells to survive under stressful conditions and can thwart therapeutic responses. Acetyl-coenzyme A (CoA plays central roles in energy production, lipid metabolism, and epigenomic modifications. Here, we show that, upon genetic deletion of Acly, the gene coding for ATP-citrate lyase (ACLY, cells remain viable and proliferate, although at an impaired rate. In the absence of ACLY, cells upregulate ACSS2 and utilize exogenous acetate to provide acetyl-CoA for de novo lipogenesis (DNL and histone acetylation. A physiological level of acetate is sufficient for cell viability and abundant acetyl-CoA production, although histone acetylation levels remain low in ACLY-deficient cells unless supplemented with high levels of acetate. ACLY-deficient adipocytes accumulate lipid in vivo, exhibit increased acetyl-CoA and malonyl-CoA production from acetate, and display some differences in fatty acid content and synthesis. Together, these data indicate that engagement of acetate metabolism is a crucial, although partial, mechanism of compensation for ACLY deficiency.

  13. ATP-Citrate Lyase Controls a Glucose-to-Acetate Metabolic Switch.

    Science.gov (United States)

    Zhao, Steven; Torres, AnnMarie; Henry, Ryan A; Trefely, Sophie; Wallace, Martina; Lee, Joyce V; Carrer, Alessandro; Sengupta, Arjun; Campbell, Sydney L; Kuo, Yin-Ming; Frey, Alexander J; Meurs, Noah; Viola, John M; Blair, Ian A; Weljie, Aalim M; Metallo, Christian M; Snyder, Nathaniel W; Andrews, Andrew J; Wellen, Kathryn E

    2016-10-18

    Mechanisms of metabolic flexibility enable cells to survive under stressful conditions and can thwart therapeutic responses. Acetyl-coenzyme A (CoA) plays central roles in energy production, lipid metabolism, and epigenomic modifications. Here, we show that, upon genetic deletion of Acly, the gene coding for ATP-citrate lyase (ACLY), cells remain viable and proliferate, although at an impaired rate. In the absence of ACLY, cells upregulate ACSS2 and utilize exogenous acetate to provide acetyl-CoA for de novo lipogenesis (DNL) and histone acetylation. A physiological level of acetate is sufficient for cell viability and abundant acetyl-CoA production, although histone acetylation levels remain low in ACLY-deficient cells unless supplemented with high levels of acetate. ACLY-deficient adipocytes accumulate lipid in vivo, exhibit increased acetyl-CoA and malonyl-CoA production from acetate, and display some differences in fatty acid content and synthesis. Together, these data indicate that engagement of acetate metabolism is a crucial, although partial, mechanism of compensation for ACLY deficiency. Copyright © 2016 The Authors. Published by Elsevier Inc. All rights reserved.

  14. NRK1 controls nicotinamide mononucleotide and nicotinamide riboside metabolism in mammalian cells.

    Science.gov (United States)

    Ratajczak, Joanna; Joffraud, Magali; Trammell, Samuel A J; Ras, Rosa; Canela, Núria; Boutant, Marie; Kulkarni, Sameer S; Rodrigues, Marcelo; Redpath, Philip; Migaud, Marie E; Auwerx, Johan; Yanes, Oscar; Brenner, Charles; Cantó, Carles

    2016-10-11

    NAD + is a vital redox cofactor and a substrate required for activity of various enzyme families, including sirtuins and poly(ADP-ribose) polymerases. Supplementation with NAD + precursors, such as nicotinamide mononucleotide (NMN) or nicotinamide riboside (NR), protects against metabolic disease, neurodegenerative disorders and age-related physiological decline in mammals. Here we show that nicotinamide riboside kinase 1 (NRK1) is necessary and rate-limiting for the use of exogenous NR and NMN for NAD + synthesis. Using genetic gain- and loss-of-function models, we further demonstrate that the role of NRK1 in driving NAD + synthesis from other NAD + precursors, such as nicotinamide or nicotinic acid, is dispensable. Using stable isotope-labelled compounds, we confirm NMN is metabolized extracellularly to NR that is then taken up by the cell and converted into NAD + . Our results indicate that mammalian cells require conversion of extracellular NMN to NR for cellular uptake and NAD + synthesis, explaining the overlapping metabolic effects observed with the two compounds.

  15. Control of biotin biosynthesis in mycobacteria by a pyruvate carboxylase dependent metabolic signal.

    Science.gov (United States)

    Lazar, Nathaniel; Fay, Allison; Nandakumar, Madhumitha; Boyle, Kerry E; Xavier, Joao; Rhee, Kyu; Glickman, Michael S

    2017-12-01

    Biotin is an essential cofactor utilized by all domains of life, but only synthesized by bacteria, fungi and plants, making biotin biosynthesis a target for antimicrobial development. To understand biotin biosynthesis in mycobacteria, we executed a genetic screen in Mycobacterium smegmatis for biotin auxotrophs and identified pyruvate carboxylase (Pyc) as required for biotin biosynthesis. The biotin auxotrophy of the pyc::tn strain is due to failure to transcriptionally induce late stage biotin biosynthetic genes in low biotin conditions. Loss of bioQ, the repressor of biotin biosynthesis, in the pyc::tn strain reverted biotin auxotrophy, as did reconstituting the last step of the pathway through heterologous expression of BioB and provision of its substrate DTB. The role of Pyc in biotin regulation required its catalytic activities and could be supported by M. tuberculosis Pyc. Quantitation of the kinetics of depletion of biotinylated proteins after biotin withdrawal revealed that Pyc is the most rapidly depleted biotinylated protein and metabolomics revealed a broad metabolic shift in wild type cells upon biotin withdrawal which was blunted in cell lacking Pyc. Our data indicate that mycobacterial cells monitor biotin sufficiency through a metabolic signal generated by dysfunction of a biotinylated protein of central metabolism. © 2017 John Wiley & Sons Ltd.

  16. Spatially resolved metabolic analysis reveals a central role for transcriptional control in carbon allocation to wood.

    Science.gov (United States)

    Roach, Melissa; Arrivault, Stéphanie; Mahboubi, Amir; Krohn, Nicole; Sulpice, Ronan; Stitt, Mark; Niittylä, Totte

    2017-06-15

    The contribution of transcriptional and post-transcriptional regulation to modifying carbon allocation to developing wood of trees is not well defined. To clarify the role of transcriptional regulation, the enzyme activity patterns of eight central primary metabolism enzymes across phloem, cambium, and developing wood of aspen (Populus tremula L.) were compared with transcript levels obtained by RNA sequencing of sequential stem sections from the same trees. Enzymes were selected on the basis of their importance in sugar metabolism and in linking primary metabolism to lignin biosynthesis. Existing enzyme assays were adapted to allow measurements from ~1 mm3 sections of dissected stem tissue. These experiments provided high spatial resolution of enzyme activity changes across different stages of wood development, and identified the gene transcripts probably responsible for these changes. In most cases, there was a clear positive relationship between transcripts and enzyme activity. During secondary cell wall formation, the increases in transcript levels and enzyme activities also matched with increased levels of glucose, fructose, hexose phosphates, and UDP-glucose, emphasizing an important role for transcriptional regulation in carbon allocation to developing aspen wood. These observations corroborate the efforts to increase carbon allocation to wood by engineering gene regulatory networks. © The Author 2017. Published by Oxford University Press on behalf of the Society for Experimental Biology.

  17. Effect of grape seed extract on postprandial oxidative status and metabolic responses in men and women with the metabolic syndrome - randomized, cross-over, placebo-controlled study

    Directory of Open Access Journals (Sweden)

    Indika Edirisinghe

    2012-12-01

    Full Text Available Objective: This investigation was undertaken to determine whether a grape seed extract (GSE that is rich in mono-, oligo- and poly- meric polyphenols would modify postprandial oxidative stress and inflammation in individuals with the metabolic syndrome (MetS.Background: MetS is known to be associated with impaired glucose tolerance and poor glycemic control. Consumption of a meal high in readily available carbohydrates and fat causes postprandial increases in glycemia and lipidemia and markers of oxidative stress, inflammation and insulin resistance. Materials/methods: After an overnight fast, twelve subjects with MetS (5 men and 7 women consumed a breakfast meal high in fat and carbohydrate in a cross-over design. A GSE (300 mg or placebo capsule was administrated 1 hr before the meal (-1 hr. Changes in plasma insulin, glucose, oxidative stress and inflammatory markers were measured hourly for 6 hr. Results: Plasma hydrophilic oxygen radical absorbance capacity (ORAC measured as the positive incremental area under the curve (-1 to 5 hr was significantly increased when the meal was preceded by GSE compared with placebo (P0.05. No changes in inflammatory markers were evident. Conclusion: These data suggest that GSE enhances postprandial plasma antioxidant status and reduces the glycemic response to a meal, high in fat and carbohydrate in subjects with the MetS.

  18. Everybody needs good neighbours

    Energy Technology Data Exchange (ETDEWEB)

    Hoffman, G. [Peabody Energy (United States)

    2006-05-15

    The paper outlines the possibilities for mines to work with surrounding communities to bring about effective land reclamation. Last year Peabody Energy teams reclaimed more than 5000 acres of land and planted nearly 750,000 trees, demonstrating that sustainable development is possible in a way that is compatible with environmental improvement in coal mining. The company has won over 20 awards over the last two years. The North Antelope Rochelle Mine in Wyoming earned a Gold Good Neighbour Award for promoting best practices in environmental conservation and mining education. The Black Mesa and Kayenta mines, which operate on Navajo and Hopi lands in Arizona, were honoured with a Silver Good Neighbour Award and a National Excellence in Mining and Reclamation Award. These mines partnered with the tribes, the Bureau of Indian Affairs and local residents to give residents access to grazing land still under Peabody's control. The Farmersburg Mine in Indiana received the Bronze Good Neighbour Award for commitment to industry education and outreach activities. 5 photos.

  19. The Good Schools Toolkit to prevent violence against children in Ugandan primary schools: study protocol for a cluster randomised controlled trial

    Science.gov (United States)

    2013-01-01

    Background We aim to evaluate the effectiveness of the Good School Toolkit, developed by Raising Voices, in preventing violence against children attending school and in improving child mental health and educational outcomes. Methods/design We are conducting a two-arm cluster randomised controlled trial with parallel assignment in Luwero District, Uganda. We will also conduct a qualitative study, a process evaluation and an economic evaluation. A total of 42 schools, representative of Luwero District, Uganda, were allocated to receive the Toolkit plus implementation support, or were allocated to a wait-list control condition. Our main analysis will involve a cross-sectional comparison of the prevalence of past-week violence from school staff as reported by children in intervention and control primary schools at follow-up. At least 60 children per school and all school staff members will be interviewed at follow-up. Data collection involves a combination of mobile phone-based, interviewer-completed questionnaires and paper-and-pen educational tests. Survey instruments include the ISPCAN Child Abuse Screening Tools to assess experiences of violence; the Strengths and Difficulties Questionnaire to measure symptoms of common childhood mental disorders; and word recognition, reading comprehension, spelling, arithmetic and sustained attention tests adapted from an intervention trial in Kenya. Discussion To our knowledge, this is the first study to rigorously investigate the effects of any intervention to prevent violence from school staff to children in primary school in a low-income setting. We hope the results will be informative across the African region and in other settings. Trial registration clinicaltrials.gov NCT01678846 PMID:23883138

  20. The Good Schools Toolkit to prevent violence against children in Ugandan primary schools: study protocol for a cluster randomised controlled trial.

    Science.gov (United States)

    Devries, Karen M; Allen, Elizabeth; Child, Jennifer C; Walakira, Eddy; Parkes, Jenny; Elbourne, Diana; Watts, Charlotte; Naker, Dipak

    2013-07-24

    We aim to evaluate the effectiveness of the Good School Toolkit, developed by Raising Voices, in preventing violence against children attending school and in improving child mental health and educational outcomes. We are conducting a two-arm cluster randomised controlled trial with parallel assignment in Luwero District, Uganda. We will also conduct a qualitative study, a process evaluation and an economic evaluation. A total of 42 schools, representative of Luwero District, Uganda, were allocated to receive the Toolkit plus implementation support, or were allocated to a wait-list control condition. Our main analysis will involve a cross-sectional comparison of the prevalence of past-week violence from school staff as reported by children in intervention and control primary schools at follow-up.At least 60 children per school and all school staff members will be interviewed at follow-up. Data collection involves a combination of mobile phone-based, interviewer-completed questionnaires and paper-and-pen educational tests. Survey instruments include the ISPCAN Child Abuse Screening Tools to assess experiences of violence; the Strengths and Difficulties Questionnaire to measure symptoms of common childhood mental disorders; and word recognition, reading comprehension, spelling, arithmetic and sustained attention tests adapted from an intervention trial in Kenya. To our knowledge, this is the first study to rigorously investigate the effects of any intervention to prevent violence from school staff to children in primary school in a low-income setting. We hope the results will be informative across the African region and in other settings. clinicaltrials.gov NCT01678846.

  1. Interaction Between the Central and Peripheral Effects of Insulin in Controlling Hepatic Glucose Metabolism in the Conscious Dog

    Science.gov (United States)

    Ramnanan, Christopher J.; Kraft, Guillaume; Smith, Marta S.; Farmer, Ben; Neal, Doss; Williams, Phillip E.; Lautz, Margaret; Farmer, Tiffany; Donahue, E. Patrick; Cherrington, Alan D.; Edgerton, Dale S.

    2013-01-01

    The importance of hypothalamic insulin action to the regulation of hepatic glucose metabolism in the presence of a normal liver/brain insulin ratio (3:1) is unknown. Thus, we assessed the role of central insulin action in the response of the liver to normal physiologic hyperinsulinemia over 4 h. Using a pancreatic clamp, hepatic portal vein insulin delivery was increased three- or eightfold in the conscious dog. Insulin action was studied in the presence or absence of intracerebroventricularly mediated blockade of hypothalamic insulin action. Euglycemia was maintained, and glucagon was clamped at basal. Both the molecular and metabolic aspects of insulin action were assessed. Blockade of hypothalamic insulin signaling did not alter the insulin-mediated suppression of hepatic gluconeogenic gene transcription but blunted the induction of glucokinase gene transcription and completely blocked the inhibition of glycogen synthase kinase-3β gene transcription. Thus, central and peripheral insulin action combined to control some, but not other, hepatic enzyme programs. Nevertheless, inhibition of hypothalamic insulin action did not alter the effects of the hormone on hepatic glucose flux (production or uptake). These data indicate that brain insulin action is not a determinant of the rapid (<4 h) inhibition of hepatic glucose metabolism caused by normal physiologic hyperinsulinemia in this large animal model. PMID:23011594

  2. Clinical and biochemical heterogeneity between patients with glycogen storage disease type IA: the added value of CUSUM for metabolic control.

    Science.gov (United States)

    Peeks, Fabian; Steunenberg, Thomas A H; de Boer, Foekje; Rubio-Gozalbo, M Estela; Williams, Monique; Burghard, Rob; Rajas, Fabienne; Oosterveer, Maaike H; Weinstein, David A; Derks, Terry G J

    2017-09-01

    To study heterogeneity between patients with glycogen storage disease type Ia (GSD Ia), a rare inherited disorder of carbohydrate metabolism caused by the deficiency of glucose-6-phosphatase (G6Pase). Descriptive retrospective study of longitudinal clinical and biochemical data and long-term complications in 20 GSD Ia patients. We included 11 patients with homozygous G6PC mutations and siblings from four families carrying identical G6PC genotypes. To display subtle variations for repeated triglyceride measurements with respect to time for individual patients, CUSUM-analysis graphs were constructed. Patients with different homozygous G6PC mutations showed important differences in height, BMI, and biochemical parameters (i.e., lactate, uric acid, triglyceride, and cholesterol concentrations). Furthermore, CUSUM-analysis predicts and displays subtle changes in longitudinal blood triglyceride concentrations. Siblings in families also displayed important differences in biochemical parameters (i.e., lactate, uric acid, triglycerides, and cholesterol concentrations) and long-term complications (i.e., liver adenomas, nephropathy, and osteopenia/osteoporosis). Differences between GSD Ia patients reflect large clinical and biochemical heterogeneity. Heterogeneity between GSD Ia patients with homozygous G6PC mutations indicate an important role of the G6PC genotype/mutations. Differences between affected siblings suggest an additional role (genetic and/or environmental) of modifying factors defining the GSD Ia phenotype. CUSUM-analysis can facilitate single-patient monitoring of metabolic control and future application of this method may improve precision medicine for patients both with GSD and remaining inherited metabolic diseases.

  3. Melatonin for Atypical Antipsychotic-Induced Metabolic Adverse Effects: A Meta-Analysis of Randomized Controlled Trials

    Directory of Open Access Journals (Sweden)

    Ashwin Kamath

    2018-01-01

    Full Text Available The objective of our study was to determine the effect of melatonin administration on atypical antipsychotic-induced metabolic adverse effects in patients with psychiatric disorders. A systematic search was performed in PUBMED, Cochrane Library, Scopus, Web of Science, and EBSCOhost electronic databases. Randomized controlled trials studying the effect of melatonin on antipsychotic-induced metabolic adverse effects were identified and subjected to meta-analysis. Four studies were included in the meta-analysis, including 57 patients on melatonin and 61 patients on placebo. Melatonin produced a significant decrease in the diastolic blood pressure compared with placebo (mean difference = −4.44 [95% CI, −7.00 to −1.88]; p=0.0007; I2 = 13%, but not the systolic blood pressure (mean difference = −4.23 [95% CI, −8.11 to −0.36]; p=0.03; I2 = 0%. Although a decrease in the body mass index was seen in the melatonin group, the difference was not significant in the random-effects analysis model. To conclude, in patients on atypical antipsychotics, melatonin at a dose of up to 5 mg/day for a treatment duration of up to 12 weeks attenuated the rise in diastolic blood pressure compared with placebo but had no significant effects on other metabolic parameters.

  4. Melatonin for Atypical Antipsychotic-Induced Metabolic Adverse Effects: A Meta-Analysis of Randomized Controlled Trials.

    Science.gov (United States)

    Kamath, Ashwin; Rather, Zahoor Ahmad

    2018-01-01

    The objective of our study was to determine the effect of melatonin administration on atypical antipsychotic-induced metabolic adverse effects in patients with psychiatric disorders. A systematic search was performed in PUBMED, Cochrane Library, Scopus, Web of Science, and EBSCOhost electronic databases. Randomized controlled trials studying the effect of melatonin on antipsychotic-induced metabolic adverse effects were identified and subjected to meta-analysis. Four studies were included in the meta-analysis, including 57 patients on melatonin and 61 patients on placebo. Melatonin produced a significant decrease in the diastolic blood pressure compared with placebo (mean difference = -4.44 [95% CI, -7.00 to -1.88]; p = 0.0007; I 2 = 13%), but not the systolic blood pressure (mean difference = -4.23 [95% CI, -8.11 to -0.36]; p = 0.03; I 2 = 0%). Although a decrease in the body mass index was seen in the melatonin group, the difference was not significant in the random-effects analysis model. To conclude, in patients on atypical antipsychotics, melatonin at a dose of up to 5 mg/day for a treatment duration of up to 12 weeks attenuated the rise in diastolic blood pressure compared with placebo but had no significant effects on other metabolic parameters.

  5. Diabetes self-management, depressive symptoms, quality of life and metabolic control in youth with type 1 diabetes in China.

    Science.gov (United States)

    Guo, Jia; Whittemore, Robin; Grey, Margaret; Wang, Jing; Zhou, Zhi-Guang; He, Guo-Ping

    2013-01-01

    To assess diabetes self-management, depressive symptoms, quality of life and metabolic control in a cohort of youth with type 1 diabetes in mainland China. Predictors of self-management and depressive symptoms were also explored. Studies have shown that adaptation to childhood chronic illness is important in determining outcomes. Few studies have been reported on the behavioural, psychosocial and physiological adaptation processes and outcomes in Chinese youth with type 1 diabetes. This is a cross-sectional study as part of a multi-site longitudinal descriptive study. Data for this report were collected at baseline. A convenience sample of 136 eligible youth was recruited during follow-up visits in hospitals in 14 major cities of Hunan Province (located in central southern mainland China) from July 2009-October 2010. Data were collected on socio-demographic background, clinical characteristics, diabetes self-management, depressive symptoms, quality of life and metabolic control. Diabetes self-management was lower in Chinese youth compared with a US cohort and was associated with insulin treatment regimen, treatment location, depressive symptoms and gender. A total of 17·6% of youth reported high depressive symptoms, and depressive symptoms were correlated with family annual revenue, school attendance, peer relationship and parent-child relationship. The mean score of global satisfaction with quality of life was 17·14 ± 3·58. The mean HbA1c was 9·68%. Living with type 1 diabetes poses considerable challenges, and Chinese youth report lower self-management than US youth and high depressive symptoms. Metabolic control and quality of life were sub-optimal. More clinic visits, treatment for high depressive symptoms and an intensive insulin regimen may improve diabetes self-management for youth with type 1 diabetes in China. Culturally appropriate interventions aimed at helping them adapt to living with the disease and improving outcomes are urgently needed. © 2012

  6. The Good School Toolkit for reducing physical violence from school staff to primary school students: a cluster-randomised controlled trial in Uganda.

    Science.gov (United States)

    Devries, Karen M; Knight, Louise; Child, Jennifer C; Mirembe, Angel; Nakuti, Janet; Jones, Rebecca; Sturgess, Joanna; Allen, Elizabeth; Kyegombe, Nambusi; Parkes, Jenny; Walakira, Eddy; Elbourne, Diana; Watts, Charlotte; Naker, Dipak

    2015-07-01

    Violence against children from school staff is widespread in various settings, but few interventions address this. We tested whether the Good School Toolkit-a complex behavioural intervention designed by Ugandan not-for-profit organisation Raising Voices-could reduce physical violence from school staff to Ugandan primary school children. We randomly selected 42 primary schools (clusters) from 151 schools in Luwero District, Uganda, with more than 40 primary 5 students and no existing governance interventions. All schools agreed to be enrolled. All students in primary 5, 6, and 7 (approximate ages 11-14 years) and all staff members who spoke either English or Luganda and could provide informed consent were eligible for participation in cross-sectional baseline and endline surveys in June-July 2012 and 2014, respectively. We randomly assigned 21 schools to receive the Good School Toolkit and 21 to a waitlisted control group in September, 2012. The intervention was implemented from September, 2012, to April, 2014. Owing to the nature of the intervention, it was not possible to mask assignment. The primary outcome, assessed in 2014, was past week physical violence from school staff, measured by students' self-reports using the International Society for the Prevention of Child Abuse and Neglect Child Abuse Screening Tool-Child Institutional. Analyses were by intention to treat, and are adjusted for clustering within schools and for baseline school-level means of continuous outcomes. The trial is registered at clinicaltrials.gov, NCT01678846. No schools left the study. At 18-month follow-up, 3820 (92·4%) of 4138 randomly sampled students participated in a cross-sectional survey. Prevalence of past week physical violence was lower in the intervention schools (595/1921, 31·0%) than in the control schools (924/1899, 48·7%; odds ratio 0·40, 95% CI 0·26-0·64, pSchool Toolkit is an effective intervention to reduce violence against children from school staff in Ugandan

  7. Effects of nutritional education on weight change and metabolic abnormalities among patients with schizophrenia in Japan: A randomized controlled trial.

    Science.gov (United States)

    Sugawara, Norio; Sagae, Toyoaki; Yasui-Furukori, Norio; Yamazaki, Manabu; Shimoda, Kazutaka; Mori, Takao; Sugai, Takuro; Matsuda, Hiroshi; Suzuki, Yutaro; Ozeki, Yuji; Okamoto, Kurefu; Someya, Toshiyuki

    2018-02-01

    Patients with schizophrenia have a higher prevalence of metabolic syndrome (MetS) than the general population. Minimizing weight gain and metabolic abnormalities in a population with an already high prevalence of obesity is of clinical and social importance. This randomized controlled trial investigated the effect of monthly nutritional education on weight change and metabolic abnormalities among patients with schizophrenia in Japan. From July 2014 to December 2014, we recruited 265 obese patients who had a DSM-IV diagnosis of schizophrenia or schizoaffective disorder. Participants were randomly assigned to a standard care (A), doctor's weight loss advice (B), or an individual nutritional education group (C) for 12 months. The prevalence of MetS and body weight were measured at baseline and 12 months. After the 12-month treatment, 189 patients were evaluated, and the prevalence of MetS based on the ATP III-A definition in groups A, B, and C was 68.9%, 67.2%, and 47.5%, respectively. Group C showed increased weight loss (3.2 ± 4.5 kg) over the 12-month study period, and the change in weight differed significantly from that of group A; additionally, 26.2% of the participants in group C lost 7% or more of their initial weight, compared with 8.2% of those in group A. Individual nutrition education provided by a dietitian was highly successful in reducing obesity in patients with schizophrenia and could be the first choice to address both weight gain and metabolic abnormalities induced by antipsychotic medications. Copyright © 2017 Elsevier Ltd. All rights reserved.

  8. Effect of Volume of Fluid Resuscitation on Metabolic Normalization in Children Presenting in Diabetic Ketoacidosis: A Randomized Controlled Trial.

    Science.gov (United States)

    Bakes, Katherine; Haukoos, Jason S; Deakyne, Sara J; Hopkins, Emily; Easter, Josh; McFann, Kim; Brent, Alison; Rewers, Arleta

    2016-04-01

    The optimal rate of fluid administration in pediatric diabetic ketoacidosis (DKA) is unknown. Our aim was to determine whether the volume of fluid administration in children with DKA influences the rate of metabolic normalization. We performed a randomized controlled trial conducted in a tertiary pediatric emergency department from December 2007 until June 2010. The primary outcome was time to metabolic normalization; secondary outcomes were time to bicarbonate normalization, pH normalization, overall length of hospital treatment, and adverse outcomes. Children between 0 and 18 years of age were eligible if they had type 1 diabetes mellitus and DKA. Patients were randomized to receive intravenous (IV) fluid at low volume (10 mL/kg bolus + 1.25 × maintenance rate) or high volume (20 mL/kg bolus + 1.5 × maintenance rate) (n = 25 in each). After adjusting for initial differences in bicarbonate levels, time to metabolic normalization was significantly faster in the higher-volume infusion group compared to the low-volume infusion group (hazard ratio [HR] = 2.0; 95% confidence interval [CI] 1.0-3.9; p = 0.04). Higher-volume IV fluid infusion appeared to hasten, to a greater extent, normalization of pH (HR = 2.5; 95% CI 1.2-5.0; p = 0.01) than normalization of serum bicarbonate (HR = 1.2; 95% CI 0.6-2.3; p = 0.6). The length of hospital treatment HR (0.8; 95% CI 0.4-1.5; p = 0.5) and time to discharge HR (0.8; 95% CI 0.4-1.5; p = 0.5) did not differ between treatment groups. Higher-volume fluid infusion in the treatment of pediatric DKA patients significantly shortened metabolic normalization time, but did not change overall length of hospital treatment. ClinicalTrials.gov ID NCT01701557. Copyright © 2016 Elsevier Inc. All rights reserved.

  9. Metabolic control in type 1 diabetes patients practicing combat sports: at least two-year follow-up study.

    Science.gov (United States)

    Benbenek-Klupa, Teresa; Matejko, Bartlomiej; Klupa, Tomasz

    2015-01-01

    It is well recognized that physical activity should be an integral part of the management of diabetes. It remains controversial, however, whether combat sports, often preferred by young individuals type 1 diabetes mellitus (T1DM), may be performed without high risk of metabolic decompensation. The aim of this observational study was to summarize a two-year follow-up period of five young male patients with T1DM practicing combat sports under the care of a physical-activity oriented specialist diabetes outpatient clinic. Of the five patients, three mixed martial arts and two kick-boxing competitors were included in the study. To control glucose in each patient, an individual approach was used that took into consideration the type of training, the sequence of the exercises, and the relative proportion of different forms of exercise. During the follow-up, glycemic control was improved and maintained in all individuals. Neither an episode of hospitalization-requiring diabetic ketoacidosis nor severe hypoglycemia occurred in these patients during the follow-up. In conclusion, an individual approach for T1DM patients practicing combat sports may result in achieving and maintaining satisfactory glycemic control without increased risk of metabolic decompensation.

  10. Colorectal cancer and its association with the metabolic syndrome: a Malaysian multi-centric case-control study.

    Science.gov (United States)

    Ulaganathan, V; Kandiah, M; Zalilah, M S; Faizal, J A; Fijeraid, H; Normayah, K; Gooi, B H; Othman, R

    2012-01-01

    Colorectal cancer (CRC) and the metabolic syndrome (MetS) are both on the rise in Malaysia. A multi-centric case-control study was conducted from December 2009 to January 2011 to determine any relationship between the two. Patients with confirmed CRC based on colonoscopy findings and cancer free controls from five local hospitals were assessed for MetS according to the International Diabetes Federation (IDF) definition. Each index case was matched for age, gender and ethnicity with two controls (140: 280). MetS among cases was highly prevalent (70.7%), especially among women (68.7%). MetS as an entity increased CRC risk by almost three fold independently (OR=2.61, 95%CI=1.53-4.47). In men MetS increased the risk of CRC by two fold (OR=2.01, 95%CI, 1.43-4.56), demonstrating an increasing trend in risk with the number of Mets components observed. This study provides evidence for a positive association between the metabolic syndrome and colorectal cancer. A prospective study on the Malaysian population is a high priority to confirm these findings.

  11. LA sprouts randomized controlled nutrition, cooking and gardening programme reduces obesity and metabolic risk in Hispanic/Latino youth.

    Science.gov (United States)

    Gatto, N M; Martinez, L C; Spruijt-Metz, D; Davis, J N

    2017-02-01

    Many programmes for children that involve gardening and nutrition components exist; however, none include experimental designs allowing more rigorous evaluation of their impact on obesity. The objective of this study is to explore the effects of a novel 12-week gardening, nutrition and cooking intervention {'LA Sprouts'} on dietary intake, obesity parameters and metabolic disease risk among low-income, primarily Hispanic/Latino youth in Los Angeles.. This study used a randomized control trial involving four elementary schools [two randomized to intervention {172, 3rd-5th grade students}; two randomized to control {147, 3rd-5th grade students}]. Classes were taught in 90-min sessions once per week for 12 weeks. Data collected at pre-intervention and post-intervention included dietary intake via food frequency questionnaire, anthropometric measures {body mass index, waist circumference}, body fat, and fasting blood samples. LA Sprouts participants compared with controls had significantly greater reductions in body mass index z-scores {-0.1 vs. -0.04, respectively; p = 0.01} and waist circumference {-1.2 vs. 0.1 cm; p obesity and metabolic risk; however, additional larger and longer-term studies are warranted. © 2016 World Obesity Federation.

  12. Metabolic effects of resistance or high-intensity interval training among glycemic control-nonresponsive children with insulin resistance.

    Science.gov (United States)

    Álvarez, C; Ramírez-Campillo, R; Ramírez-Vélez, R; Martínez, C; Castro-Sepúlveda, M; Alonso-Martínez, A; Izquierdo, M

    2018-01-01

    Little evidence exists on which variables of body composition or muscular strength mediates more glucose control improvements taking into account inter-individual metabolic variability to different modes of exercise training. We examined 'mediators' to the effects of 6-weeks of resistance training (RT) or high-intensity interval training (HIT) on glucose control parameters in physically inactive schoolchildren with insulin resistance (IR). Second, we also determined both training-induce changes and the prevalence of responders (R) and non-responders (NR) to decrease the IR level. Fifty-six physically inactive children diagnosed with IR followed a RT or supervised HIT program for 6 weeks. Participants were classified based on ΔHOMA-IR into glycemic control R (decrease in homeostasis model assessment-IR (HOMA-IR) training-induced changes to glucose control parameters; and third the report of R and NR to improve body composition, cardiovascular, metabolic and performance variables. Mediation analysis revealed that improvements (decreases) in abdominal fat by the waist circumference can explain more the effects (decreases) of HOMA-IR in physically inactive schoolchildren under RT or HIT regimes. The same analysis showed that increased one-maximum repetition leg-extension was correlated with the change in HOMA-IR (β=-0.058; P=0.049). Furthermore, a change in the waist circumference fully mediated the dose-response relationship between changes in the leg-extension strength and HOMA-IR (β'=-0.004; P=0.178). RT or HIT were associated with significant improvements in body composition, muscular strength, blood pressure and cardiometabolic parameters irrespective of improvement in glycemic control response. Both glucose control RT-R and HIT-R (respectively), had significant improvements in mean HOMA-IR, mean muscular strength leg-extension and mean measures of adiposity. The improvements in the lower body strength and the decreases in waist circumference can explain more

  13. A Nested Case-Control Study of Metabolically Defined Body Size Phenotypes and Risk of Colorectal Cancer in the European Prospective Investigation into Cancer and Nutrition (EPIC.

    Directory of Open Access Journals (Sweden)

    Neil Murphy

    2016-04-01

    Full Text Available Obesity is positively associated with colorectal cancer. Recently, body size subtypes categorised by the prevalence of hyperinsulinaemia have been defined, and metabolically healthy overweight/obese individuals (without hyperinsulinaemia have been suggested to be at lower risk of cardiovascular disease than their metabolically unhealthy (hyperinsulinaemic overweight/obese counterparts. Whether similarly variable relationships exist for metabolically defined body size phenotypes and colorectal cancer risk is unknown.The association of metabolically defined body size phenotypes with colorectal cancer was investigated in a case-control study nested within the European Prospective Investigation into Cancer and Nutrition (EPIC study. Metabolic health/body size phenotypes were defined according to hyperinsulinaemia status using serum concentrations of C-peptide, a marker of insulin secretion. A total of 737 incident colorectal cancer cases and 737 matched controls were divided into tertiles based on the distribution of C-peptide concentration amongst the control population, and participants were classified as metabolically healthy if below the first tertile of C-peptide and metabolically unhealthy if above the first tertile. These metabolic health definitions were then combined with body mass index (BMI measurements to create four metabolic health/body size phenotype categories: (1 metabolically healthy/normal weight (BMI < 25 kg/m2, (2 metabolically healthy/overweight (BMI ≥ 25 kg/m2, (3 metabolically unhealthy/normal weight (BMI < 25 kg/m2, and (4 metabolically unhealthy/overweight (BMI ≥ 25 kg/m2. Additionally, in separate models, waist circumference measurements (using the International Diabetes Federation cut-points [≥80 cm for women and ≥94 cm for men] were used (instead of BMI to create the four metabolic health/body size phenotype categories. Statistical tests used in the analysis were all two-sided, and a p-value of <0.05 was

  14. Serum GGT activity and hsCRP level in patients with type 2 diabetes mellitus with good and poor glycemic control: An evidence linking oxidative stress, inflammation and glycemic control.

    Science.gov (United States)

    Gohel, Mukesh G; Chacko, Anusha N

    2013-12-20

    Diabetes is undoubtedly one of the most challenging health problems in 21st century. Understanding the pathogenesis and preventing long term complications have been major goals of research in diabetes mellitus (DM). Research in the past few years has linked oxidative stress and inflammation to beta cell dysfunction. Aim of this study is to evaluate serum gamma-glutamyl transferase (GGT) activity (marker of oxidative stress) and high sensitivity C reactive protein (hsCRP) level (an inflammatory marker) in type 2 DM subjects with good and poor glycemic control. Further, we investigated correlation between serum GGT and hsCRP level with glycemic control (FBS, PP2BS, HbA1c) in subjects. A cross sectional study consists of 150 patients out of them 50 patients having type 2 DM with good control (Group II), 50 patients with type 2 DM with poor control (Group III) and 50 normal healthy control (Group I) were selected. Serum GGT, serum hsCRP, FBS, PP2BS, HbA1c, and other biochemical investigations include serum liver enzymes and lipids were measured. Mean serum GGT and hsCRP concentration were statistically significantly higher in group III patients compared to group I and group II subjects as well as increased in group II compared to group I (p stress and inflammation appears to be a key component and also associated with poor glycemic control and further pathogenesis of diabetes and its complications. All our finding suggesting a link between oxidative stress, inflammation and glycemic control in patient with type 2 diabetes mellitus.

  15. The effect of metformin in overweight patients with type 1 diabetes and poor metabolic control

    DEFF Research Database (Denmark)

    Jacobsen, Iben Brock; Henriksen, Jan Erik; Beck-Nielsen, Henning

    2009-01-01

    Metformin as adjunct to intensive insulin therapy may improve glucose metabolism and thereby prevent the development of cardiovascular risk factors in patients with type 1 diabetes. Double-blinded intervention with 2000 mg metformin or placebo daily in 24 type 1 diabetic patients as adjunct...... to intensive insulin therapy. Primary endpoint was HbA1c, while secondary endpoints were body weight, frequency of hypoglycaemia, blood pressure, lipids, insulin dosage and self-monitored blood glucose profiles were measured. After 24 weeks, no difference in HbA1c was seen between the metformin and placebo...

  16. 13C MRS Studies of the Control of Hepatic Glycogen Metabolism at High Magnetic Fields

    Directory of Open Access Journals (Sweden)

    Corin O. Miller

    2017-06-01

    Full Text Available Introduction: Glycogen is the primary intracellular storage form of carbohydrates. In contrast to most tissues where stored glycogen can only supply the local tissue with energy, hepatic glycogen is mobilized and released into the blood to maintain appropriate circulating glucose levels, and is delivered to other tissues as glucose in response to energetic demands. Insulin and glucagon, two current targets of high interest in the pharmaceutical industry, are well-known glucose-regulating hormones whose primary effect in liver is to modulate glycogen synthesis and breakdown. The purpose of these studies was to develop methods to measure glycogen metabolism in real time non-invasively both in isolated mouse livers, and in non-human primates (NHPs using 13C MRS.Methods: Livers were harvested from C57/Bl6 mice and perfused with [1-13C] Glucose. To demonstrate the ability to measure acute changes in glycogen metabolism ex-vivo, fructose, glucagon, and insulin were administered to the liver ex-vivo. The C1 resonance of glycogen was measured in real time with 13C MRS using an 11.7T (500 MHz NMR spectrometer. To demonstrate the translatability of this approach, NHPs (male rhesus monkeys were studied in a 7 T Philips MRI using a partial volume 1H/13C imaging coil. NPHs were subjected to a variable IV infusion of [1-13C] glucose (to maintain blood glucose at 3-4x basal, along with a constant 1 mg/kg/min infusion of fructose. The C1 resonance of glycogen was again measured in real time with 13C MRS. To demonstrate the ability to measure changes in glycogen metabolism in vivo, animals received a glucagon infusion (1 μg/kg bolus followed by 40 ng/kg/min constant infusion half way through the study on the second study session.Results: In both perfused mouse livers and in NHPs, hepatic 13C-glycogen synthesis (i.e., monotonic increases in the 13C-glycogen NMR signal was readily detected. In both paradigms, addition of glucagon resulted in cessation of glycogen

  17. Metabolic Control, Nutrition Knowledge, Attitude and Practice in Non-Insulin-dependent Diabetic Patients from Kohgiluyeh and Boyer-Ahmad Province, South-West of Iran

    Directory of Open Access Journals (Sweden)

    Janmohamad Malekzadeh

    2016-07-01

    Full Text Available Background and Objectives: Diabetes mellitus is among the most common causes of mortality in the world and an important risk factor for chronic kidney disease, foot amputation, ischemic heart disease and blindness among older adults. Diabetic patients mostly develop hyperlipidemia, which can result in cardiovascular diseases. Patient’s knowledge, attitude and practices toward diet are the core center for diabetes control and affect their metabolic control and complications. In the present study, we measured nutritional knowledge, attitude and practices and their relations to serum lipids, HbA1C, and fasting blood glucose in diabetic patients of Boirahmad County, southwest of Iran, where many people encounter increasing prevalence of diabetes. Materials and Methods: 198 IDDM patients from the rural and urban areas of Boirahmad County were invited to the health centers to be checked for their fasting blood glucose, serum total cholesterol, serum HDL cholesterol, serum triglyceride and also serum glycosylated hemoglobin. Their knowledge, attitude, and practices toward the diabetic diet were assessed using a validated questionnaire. The obtained scores were classified into three categories (Poor, average, and Good to show their knowledge, attitude and practice levels, and the serum parameters were compared between the levels to show the relevancies. Results: Our data showed that the patients’ knowledge and attitude on diabetic nutrition are mostly at the average level (79.3% and 47.1%, respectively but their practice scores are mostly at the poor level (43.8%, and just a minor proportion of the patients are at the appropriate levels (15.3, 33, and 23.1% of knowledge, attitude and practices, respectively. In addition, we found a significant reverse relationship between the patients’ nutritional knowledge and  serum HbA1C (p=0.003, and also between their attitude and serum triglyceride (p<0.05. Conclusions: Our data suggest that the knowledge

  18. Metabolic and cardiovascular risk in patients with a history of differentiated thyroid carcinoma: A case-controlled cohort study.

    Science.gov (United States)

    Giusti, Massimo; Mortara, Lorenzo; Degrandi, Roberta; Cecoli, Francesca; Mussap, Michele; Rodriguez, Guido; Ferone, Diego; Minuto, Francesco

    2008-09-29

    Hyperthyroidism seems to increase metabolic and cardiovascular risk, while the effects of sub-clinical hyperthyroidism are controversial. We evaluated metabolic and cardiovascular parameters in differentiated thyroid carcinoma (DTC) patients with suppressed thyrotropin (TSH) due to levo-thyroxine (L-T4) therapy. We studied DTC patients and, as a control group, patients with a history of surgery for non-malignant thyroid pathology. Significantly higher insulin and lower HDL-cholesterol levels were recorded in DTC subjects. In both groups, insulin levels were significantly related with body mass index (BMI) but not with age or L-T4 dosage. In DTC patients, a significant negative correlation was seen between HDL-cholesterol and BMI or L-T4 dosage. In both groups, intima-media thickness (IMT) correlated positively with age, BMI, glucose levels and systolic blood pressure. In DTC patients, increased IMT was significantly correlated with glycated hemoglobin (HbA1c), cholesterol and triglycerides. In DTC patients, C-reactive protein correlated positively with insulin, insulin resistance, triglycerides and systolic blood pressure, and negatively with HDL-cholesterol. In both DTC and control subjects, fibrinogen correlated positively with age, BMI, increased IMT, HbA1c and systolic blood pressure. In DTC subjects, plasma fibrinogen concentrations correlated positively with insulin resistance, cholesterol and LDL-cholesterol, and negatively with TSH levels. Our data confirm that the favorable evolution of DTC can be impaired by a high incidence of abnormal metabolic and cardiovascular data that are, at least in part, related to L-T4 therapy. These findings underline the need for adequate L-T4 titration.

  19. Comparative genome analysis of central nitrogen metabolism and its control by GlnR in the class Bacilli

    Directory of Open Access Journals (Sweden)

    Kormelink Tom

    2012-05-01

    Full Text Available Abstract Background The assimilation of nitrogen in bacteria is achieved through only a few metabolic conversions between alpha-ketoglutarate, glutamate and glutamine. The enzymes that catalyze these conversions are glutamine synthetase, glutaminase, glutamate dehydrogenase and glutamine alpha-ketoglutarate aminotransferase. In low-GC Gram-positive bacteria the transcriptional control over the levels of the related enzymes is mediated by four regulators: GlnR, TnrA, GltC and CodY. We have analyzed the genomes of all species belonging to the taxonomic families Bacillaceae, Listeriaceae, Staphylococcaceae, Lactobacillaceae, Leuconostocaceae and Streptococcaceae to determine the diversity in central nitrogen metabolism and reconstructed the regulation by GlnR. Results Although we observed a substantial difference in the extent of central nitrogen metabolism in the various species, the basic GlnR regulon was remarkably constant and appeared not affected by the presence or absence of the other three main regulators. We found a conserved regulatory association of GlnR with glutamine synthetase (glnRA operon, and the transport of ammonium (amtB-glnK and glutamine/glutamate (i.e. via glnQHMP, glnPHQ, gltT, alsT. In addition less-conserved associations were found with, for instance, glutamate dehydrogenase in Streptococcaceae, purine catabolism and the reduction of nitrite in Bacillaceae, and aspartate/asparagine deamination in Lactobacillaceae. Conclusions Our analyses imply GlnR-mediated regulation in constraining the import of ammonia/amino-containing compounds and the production of intracellular ammonia under conditions of high nitrogen availability. Such a role fits with the intrinsic need for tight control of ammonia levels to limit futile cycling.

  20. Effects of Tight Versus Non Tight Control of Metabolic Acidosis on Early Renal Function After Kidney Transplantation

    Directory of Open Access Journals (Sweden)

    Farhad Etezadi

    2012-09-01

    Full Text Available Background Recently, several studies have been conducted to determine the optimal strategy for intraoperative fluid replacement therapy in renal transplantation surgery. Since infusion of sodium bicarbonate as a buffer seems to be safer than other buffer compounds (lactate, gluconate, acetatethat indirectly convert into it within the liver, We hypothesized tight control of metabolic acidosis by infusion of sodium bicarbonate may improve early post-operative renal function in renal transplant recipients. Methods:120 patients were randomly divided into two equal groups. In group A, bicarbonate was infused intra-operatively according to Base Excess (BE measurements to achieve the normal values of BE (5 to +5 mEq/L. In group B, infusion of bicarbonate was allowed only in case of severe metabolic acidosis (BE [less than or equal to] 15 mEq/L or bicarbonate [less than or equal to] 10 mEq/L or PH [less than or equal to] 7.15. Minute ventilation was adjusted to keep PaCO2 within the normal range. Primary end-point was sampling of serum creatinine level in first, second, third and seventh post-operative days for statistical comparison between groups. Secondary objectives were comparison of cumulative urine volumes in the first 24 h of post-operative period and serum BUN levels which were obtained in first, second, third and seventh post-operative days. Results:In group A, all of consecutive serum creatinine levels were significantly lower in comparison with group B. With regard to secondary outcomes, no significant difference between groups was observed. Conclusion:Intra-operative tight control of metabolic acidosis by infusion of Sodium Bicarbonate in renal transplant recipients may improve early post-operative renal function.

  1. Effects of tight versus non tight control of metabolic acidosis on early renal function after kidney transplantation

    Directory of Open Access Journals (Sweden)

    Etezadi Farhad

    2012-09-01

    Full Text Available Abstract Background Recently, several studies have been conducted to determine the optimal strategy for intra-operative fluid replacement therapy in renal transplantation surgery. Since infusion of sodium bicarbonate as a buffer seems to be safer than other buffer compounds (lactate, gluconate, acetatethat indirectly convert into it within the liver, We hypothesized tight control of metabolic acidosis by infusion of sodium bicarbonate may improve early post-operative renal function in renal transplant recipients. Methods 120 patients were randomly divided into two equal groups. In group A, bicarbonate was infused intra-operatively according to Base Excess (BE measurements to achieve the normal values of BE (−5 to +5 mEq/L. In group B, infusion of bicarbonate was allowed only in case of severe metabolic acidosis (BE ≤ −15 mEq/L or bicarbonate ≤ 10 mEq/L or PH ≤ 7.15. Minute ventilation was adjusted to keep PaCO2 within the normal range. Primary end-point was sampling of serum creatinine level in first, second, third and seventh post-operative days for statistical comparison between groups. Secondary objectives were comparison of cumulative urine volumes in the first 24 h of post-operative period and serum BUN levels which were obtained in first, second, third and seventh post-operative days. Results In group A, all of consecutive serum creatinine levels were significantly lower in comparison with group B. With regard to secondary outcomes, no significant difference between groups was observed. Conclusion Intra-operative tight control of metabolic acidosis by infusion of Sodium Bicarbonate in renal transplant recipients may improve early post-operative renal function.

  2. Metabolic and cardiovascular risk in patients with a history of differentiated thyroid carcinoma: A case-controlled cohort study

    Directory of Open Access Journals (Sweden)

    Giusti Massimo

    2008-09-01

    Full Text Available Abstract Hyperthyroidism seems to increase metabolic and cardiovascular risk, while the effects of sub-clinical hyperthyroidism are controversial. We evaluated metabolic and cardiovascular parameters in differentiated thyroid carcinoma (DTC patients with suppressed thyrotropin (TSH due to levo-thyroxine (L-T4 therapy. We studied DTC patients and, as a control group, patients with a history of surgery for non-malignant thyroid pathology. Significantly higher insulin and lower HDL-cholesterol levels were recorded in DTC subjects. In both groups, insulin levels were significantly related with body mass index (BMI but not with age or L-T4 dosage. In DTC patients, a significant negative correlation was seen between HDL-cholesterol and BMI or L-T4 dosage. In both groups, intima-media thickness (IMT correlated positively with age, BMI, glucose levels and systolic blood pressure. In DTC patients, increased IMT was significantly correlated with glycated hemoglobin (HbA1c, cholesterol and triglycerides. In DTC patients, C-reactive protein correlated positively with insulin, insulin resistance, triglycerides and systolic blood pressure, and negatively with HDL-cholesterol. In both DTC and control subjects, fibrinogen correlated positively with age, BMI, increased IMT, HbA1c and systolic blood pressure. In DTC subjects, plasma fibrinogen concentrations correlated positively with insulin resistance, cholesterol and LDL-cholesterol, and negatively with TSH levels. Our data confirm that the favorable evolution of DTC can be impaired by a high incidence of abnormal metabolic and cardiovascular data that are, at least in part, related to L-T4 therapy. These findings underline the need for adequate L-T4 titration.

  3. Caloric restriction alters the metabolic response to a mixed-meal: results from a randomized, controlled trial.

    Directory of Open Access Journals (Sweden)

    Kim M Huffman

    Full Text Available To determine if caloric restriction (CR would cause changes in plasma metabolic intermediates in response to a mixed meal, suggestive of changes in the capacity to adapt fuel oxidation to fuel availability or metabolic flexibility, and to determine how any such changes relate to insulin sensitivity (S(I.Forty-six volunteers were randomized to a weight maintenance diet (Control, 25% CR, or 12.5% CR plus 12.5% energy deficit from structured aerobic exercise (CR+EX, or a liquid calorie diet (890 kcal/d until 15% reduction in body weightfor six months. Fasting and postprandial plasma samples were obtained at baseline, three, and six months. A targeted mass spectrometry-based platform was used to measure concentrations of individual free fatty acids (FFA, amino acids (AA, and acylcarnitines (AC. S(I was measured with an intravenous glucose tolerance test.Over three and six months, there were significantly larger differences in fasting-to-postprandial (FPP concentrations of medium and long chain AC (byproducts of FA oxidation in the CR relative to Control and a tendency for the same in CR+EX (CR-3 month P = 0.02; CR-6 month P = 0.002; CR+EX-3 month P = 0.09; CR+EX-6 month P = 0.08. After three months of CR, there was a trend towards a larger difference in FPP FFA concentrations (P = 0.07; CR-3 month P = 0.08. Time-varying differences in FPP concentrations of AC and AA were independently related to time-varying S(I (P<0.05 for both.Based on changes in intermediates of FA oxidation following a food challenge, CR imparted improvements in metabolic flexibility that correlated with improvements in S(I.ClinicalTrials.gov NCT00099151.

  4. Impact of a structured multicomponent educational intervention program on metabolic control of patients with type 2 diabetes.

    Science.gov (United States)

    do Rosário Pinto, Maria; Parreira, Pedro Miguel Dinis Santos; Basto, Marta Lima; Dos Santos Mendes Mónico, Lisete

    2017-12-15

    Diabetes is one of the most common metabolic disorders, with a high prevalence of patients with poor metabolic control. Worldwide, evidence highlights the importance of developing and implementing educational interventions that can reduce this burden. The main objective of this study was to analyse the impact of a lifestyle centred intervention on glycaemic control of poorly controlled type 2 diabetic patients, followed in a Community Care Centre. A type 2 experimental design was conducted over 6 months, including 122 adults with HbA1c ≥ 7.5%, randomly allocated into Experimental group (EG) or Control Group (CG). EG patients attended a specific Educational Program while CG patients frequented usual care. Personal and health characterization variables, clinical metrics and self-care activities were measured before and after the implementation of the intervention. Analysis was done by comparing gains between groups (CG vs EG) through differential calculations (post minus pre-test results) and Longitudinal analysis. Statistical differences were obtained between groups for HbA1c and BMI: EG had a decrease in 11% more (effect-size r2 = .11) than CG for HbA1c (p values [Wilks' ʎ = .900; F(1,59) = 6.57; p = .013; ηp2 = .100; observed power = .713]; systolic Blood pressure [Wilks' ʎ = .735; F(1,61) = 21.94; p educational intervention program by itself, beyond standard educational approach alone, supported in a Longitudinal analysis that controlled variables statistically associated with clinical metrics in pre-test measures, has demonstrated its effectiveness in improving HbA1c, BMI and Blood pressure values. RBR-8ns8pb . (Retrospectively registered: October 30,2017).

  5. Control of creatine metabolism by HIF is an endogenous mechanism of barrier regulation in colitis.

    Science.gov (United States)

    Glover, Louise E; Bowers, Brittelle E; Saeedi, Bejan; Ehrentraut, Stefan F; Campbell, Eric L; Bayless, Amanda J; Dobrinskikh, Evgenia; Kendrick, Agnieszka A; Kelly, Caleb J; Burgess, Adrianne; Miller, Lauren; Kominsky, Douglas J; Jedlicka, Paul; Colgan, Sean P

    2013-12-03

    Mucosal surfaces of the lower gastrointestinal tract are subject to frequent, pronounced fluctuations in oxygen tension, particularly during inflammation. Adaptive responses to hypoxia are orchestrated largely by the hypoxia-inducible transcription factors (HIFs). As HIF-1α and HIF-2α are coexpressed in mucosal epithelia that constitute the barrier between the lumen and the underlying immune milieu, we sought to define the discrete contribution of HIF-1 and HIF-2 transactivation pathways to intestinal epithelial cell homeostasis. The present study identifies creatine kinases (CKs), key metabolic enzymes for rapid ATP generation via the phosphocreatine-creatine kinase (PCr/CK) system, as a unique gene family that is coordinately regulated by HIF. Cytosolic CKs are expressed in a HIF-2-dependent manner in vitro and localize to apical intestinal epithelial cell adherens junctions, where they are critical for junction assembly and epithelial integrity. Supplementation with dietary creatine markedly ameliorated both disease severity and inflammatory responses in colitis models. Further, enzymes of the PCr/CK metabolic shuttle demonstrate dysregulated mucosal expression in a subset of ulcerative colitis and Crohn disease patients. These findings establish a role for HIF-regulated CK in epithelial homeostasis and reveal a fundamental link between cellular bioenergetics and mucosal barrier.

  6. Timing of food intake during simulated night shift impacts glucose metabolism: A controlled study.

    Science.gov (United States)

    Grant, Crystal L; Coates, Alison M; Dorrian, Jillian; Kennaway, David J; Wittert, Gary A; Heilbronn, Leonie K; Pajcin, Maja; Della Vedova, Chris; Gupta, Charlotte C; Banks, Siobhan

    2017-01-01

    Eating during the night may increase the risk for obesity and type 2 diabetes in shift workers. This study examined the impact of either eating or not eating a meal at night on glucose metabolism. Participants underwent four nights of simulated night work (SW1-4, 16:00-10:00 h, night (NE; n = 4, meals; 07:00, 19:00 and 01:30 h) or not eating at night (NEN; n = 7, meals; 07:00 h, 09:30, 16:10 and 19:00 h) condition. Meal tolerance tests were conducted post breakfast on pre-night shift (PRE), SW4 and following return to day shift (RTDS), and glucose and insulin area under the curve (AUC) were calculated. Mixed-effects ANOVAs were used with fixed effects of condition and day, and their interactions, and a random effect of subject identifier on the intercept. Fasting glucose and insulin were not altered by day or condition. There were significant effects of day and condition × day (both p night (p = 0.040) and not eating at night (p = 0.006) conditions. Results in this small, healthy sample suggest that not eating at night may limit the metabolic consequences of simulated night work. Further study is needed to explore whether matching food intake to the biological clock could reduce the burden of type 2 diabetes in shift workers.

  7. Control of amino acid transport coordinates metabolic reprogramming in T-cell malignancy.

    Science.gov (United States)

    Grzes, K M; Swamy, M; Hukelmann, J L; Emslie, E; Sinclair, L V; Cantrell, D A

    2017-12-01

    This study explores the regulation and importance of System L amino acid transport in a murine model of T-cell acute lymphoblastic leukemia (T-ALL) caused by deletion of phosphatase and tensin homolog deleted on chromosome 10 (PTEN). There has been a strong focus on glucose transport in leukemias but the present data show that primary T-ALL cells have increased transport of multiple nutrients. Specifically, increased leucine transport in T-ALL fuels mammalian target of rapamycin complex 1 (mTORC1) activity which then sustains expression of hypoxia inducible factor-1α (HIF1α) and c-Myc; drivers of glucose metabolism in T cells. A key finding is that PTEN deletion and phosphatidylinositol (3,4,5)-trisphosphate (PtdIns(3,4,5)P 3 ) accumulation is insufficient to initiate leucine uptake, mTORC1 activity, HIF1α or c-Myc expression in T cells and hence cannot drive T-ALL metabolic reprogramming. Instead, a key regulator for leucine transport in T-ALL is identified as NOTCH. Mass spectrometry based proteomics identifies SLC7A5 as the predominant amino acid transporter in primary PTEN -/- T-ALL cells. Importantly, expression of SLC7A5 is critical for the malignant transformation induced by PTEN deletion. These data reveal the importance of regulated amino acid transport for T-cell malignancies, highlighting how a single amino acid transporter can have a key role.

  8. Phosphate Metabolism in CKD Stages 3–5: Dietary and Pharmacological Control

    Directory of Open Access Journals (Sweden)

    Markus Ketteler

    2011-01-01

    Full Text Available When compared to the available information for patients on dialysis (CKD stage 5D, data on the epidemiology and appropriate treatment of calcium and phosphate metabolism in the predialysis stages of chronic kidney disease (CKD are quite limited. Perceptible derangements of calcium and phosphate levels start to become apparent when GFR falls below 30 mL/min in some, but not all, patients. However, hyperphosphatemia may be a significant morbidity and mortality risk predictor in predialysis CKD stages. The RIND study, evaluating progression of coronary artery calcification in incident hemodialysis patients, indirectly demonstrated that vascular calcification processes start to manifest in CKD patients prior to the dialysis stage, which may be closely linked to early and invisible derangements in calcium and phosphate homeostasis. Novel insights into the pathophysiology of calcium and phosphate handling such as the discovery of FGF23 and other phosphatonins suggest that a more complex assessment of phosphate balance is warranted, possibly including measurements of fractional phosphate excretion and phosphatonin levels in order to appropriately evaluate disordered metabolism in earlier stages of kidney disease. As a consequence, early and preventive treatment approaches may have to be developed for patients in CKD stages 3-5 to halt progression of CKD-MBD.

  9. Glycogen Synthase Kinase-3 is involved in glycogen metabolism control and embryogenesis of Rhodnius prolixus.

    Science.gov (United States)

    Mury, Flávia B; Lugon, Magda D; DA Fonseca, Rodrigo Nunes; Silva, Jose R; Berni, Mateus; Araujo, Helena M; Fontenele, Marcio Ribeiro; Abreu, Leonardo Araujo DE; Dansa, Marílvia; Braz, Glória; Masuda, Hatisaburo; Logullo, Carlos

    2016-10-01

    Rhodnius prolixus is a blood-feeding insect that transmits Trypanosoma cruzi and Trypanosoma rangeli to vertebrate hosts. Rhodnius prolixus is also a classical model in insect physiology, and the recent availability of R. prolixus genome has opened new avenues on triatomine research. Glycogen synthase kinase 3 (GSK-3) is classically described as a key enzyme involved in glycogen metabolism, also acting as a downstream component of the Wnt pathway during embryogenesis. GSK-3 has been shown to be highly conserved among several organisms, mainly in the catalytic domain region. Meanwhile, the role of GSK-3 during R. prolixus embryogenesis or glycogen metabolism has not been investigated. Here we show that chemical inhibition of GSK-3 by alsterpaullone, an ATP-competitive inhibitor of GSK3, does not affect adult survival rate, though it alters oviposition and egg hatching. Specific GSK-3 gene silencing by dsRNA injection in adult females showed a similar phenotype. Furthermore, bright field and 4'-6-diamidino-2-phenylindole (DAPI) staining analysis revealed that ovaries and eggs from dsGSK-3 injected females exhibited specific morphological defects. We also demonstrate that glycogen content was inversely related to activity and transcription levels of GSK-3 during embryogenesis. Lastly, after GSK-3 knockdown, we observed changes in the expression of the Wingless (Wnt) downstream target β-catenin as well as in members of other pathways such as the receptor Notch. Taken together, our results show that GSK-3 regulation is essential for R. prolixus oogenesis and embryogenesis.

  10. Newborn Urinary Metabolic Signatures of Prematurity and Other Disorders: A Case Control Study.

    Science.gov (United States)

    Diaz, Sílvia O; Pinto, Joana; Barros, António S; Morais, Elisabete; Duarte, Daniela; Negrão, Fátima; Pita, Cristina; Almeida, Maria do Céu; Carreira, Isabel M; Spraul, Manfred; Gil, Ana M

    2016-01-04

    This work assesses the urinary metabolite signature of prematurity in newborns by nuclear magnetic resonance (NMR) spectroscopy, while establishing the role of possible confounders and signature specificity, through comparison to other disorders. Gender and delivery mode are shown to impact importantly on newborn urine composition, their analysis pointing out at specific metabolite variations requiring consideration in unmatched subject groups. Premature newborns are, however, characterized by a stronger signature of varying metabolites, suggestive of disturbances in nucleotide metabolism, lung surfactants biosynthesis and renal function, along with enhancement of tricarboxylic acid (TCA) cycle activity, fatty acids oxidation, and oxidative stress. Comparison with other abnormal conditions (respiratory depression episode, large for gestational age, malformations, jaundice and premature rupture of membranes) reveals that such signature seems to be largely specific of preterm newborns, showing that NMR metabolomics can retrieve particular disorder effects, as well as general stress effects. These results provide valuable novel information on the metabolic impact of prematurity, contributing to the better understanding of its effects on the newborn's state of health.

  11. HOW GOOD IS GOODS AND SERVICES TAX

    OpenAIRE

    Dr. Sreemoyee Guha Roy

    2016-01-01

    Goods and Services Tax is a broad based and a single comprehensive tax levied on goods and services consumed in an economy. GST is levied at every stage of the production-distribution chain with applicable set offs in respect of the tax remitted at previous stages. It is basically a tax on final consumption. The Goods and Services Tax (GST) is a value added tax to be implemented in India, the decision on which is pending. GST is the only indirect tax that directly affects all sectors and sect...

  12. Alteration patterns of brain glucose metabolism: comparisons of healthy controls, subjective memory impairment and mild cognitive impairment.

    Science.gov (United States)

    Song, In-Uk; Choi, Eun Kyoung; Oh, Jin Kyoung; Chung, Yong-An; Chung, Sung-Woo

    2016-01-01

    Some groups have focused on the detection and management of subjective memory impairment (SMI) as the stage that precedes mild cognitive impairment (MCI). However, there have been few clinical studies that have examined biomarkers of SMI to date. To investigate the differences in glucose metabolism as a prodromal marker of dementia in patients with SMI, MCI, and healthy controls using brain F-18 fluoro-2-deoxyglucose positron emission tomography (FDG-PET). Sixty-eight consecutive patients with SMI, 47 patients with MCI, and 42 age-matched healthy subjects were recruited. All subjects underwent FDG-PET and detailed neuropsychological testing. FDG-PET images were analyzed using the statistical parametric mapping (SPM) program. FDG-PET analysis showed glucose hypometabolism in the periventricular regions of patients with SMI and in the parietal, precentral frontal, and periventricular regions of patients with MCI compared with healthy controls. Interestingly, hypometabolism on FDG-PET was noted in the parietal and precentral frontal regions in MCI patients compared to SMI patients. The results suggest that hypometabolism in the periventricular regions as seen on FDG-PET may play a role as a predictive biomarker of pre-dementia, and the extension of reduced glucose metabolism into parietal regions likely reflects progression of cognitive deterioration. © The Foundation Acta Radiologica 2014.

  13. Classical and Non-Classical Roles for Pre-Receptor Control of DHT Metabolism in Prostate Cancer Progression.

    Science.gov (United States)

    Zhang, Ailin; Zhang, Jiawei; Plymate, Stephen; Mostaghel, Elahe A

    2016-04-01

    Androgens play an important role in prostate cancer (PCa) development and progression. Accordingly, androgen deprivation therapy remains the front-line treatment for locally recurrent or advanced PCa, but patients eventually relapse with the lethal form of the disease termed castration resistant PCa (CRPC). Importantly, castration does not eliminate androgens from the prostate tumor microenvironment which is characterized by elevated tissue androgens that are well within the range capable of activating the androgen receptor (AR). In this mini-review, we discuss emerging data that suggest a role for the enzymes mediating pre-receptor control of dihydrotestosterone (DHT) metabolism, including AKR1C2, HSD17B6, HSD17B10, and the UGT family members UGT2B15 and UGT2B17, in controlling intratumoral androgen levels, and thereby influencing PCa progression. We review the expression of steroidogenic enzymes involved in this pathway in primary PCa and CRPC, the activity and regulation of these enzymes in PCa experimental models, and the impact of genetic variation in genes mediating pre-receptor DHT metabolism on PCa risk. Finally, we discuss recent data that suggests several of these enzymes may also play an unrecognized role in CRPC progression separate from their role in androgen inactivation.

  14. [Effect of meal frequency and carbohydrate intake on the metabolic control of patients with type 2 diabetes mellitus].

    Science.gov (United States)

    Leiva, Tamara; Basfi-Fer, Karen; Rojas, Pamela; Carrasco, Fernando; Ruz O, Manuel

    2016-10-01

    Increasing meal frequency is commonly used in the clinical practice as part of the nutritional treatment of patients with type 2 Diabetes Mellitus (DM2), although its effect on metabolic control parameters is controversial. To evaluate the association of energy intake, meal frequency, and amount of carbohydrates with fasting plasma glucose and glycosylated hemoglobin in a group of patients with DM2 without insulin therapy. Dietary intake was evaluated in 60 subjects with DM2 through three-day food records. The meal frequency was estimated establishing the main meal times considering snacks. Meal frequency was 4.7 ± 1.1 times per day. There was a positive association between glycosylated and fasting blood glucose levels (p Meal frequency was associated with energy intake (p meal frequency, available carbohydrates and energy intake, body mass index and fasting plasma glucose were analyzed in a multiple linear regression model, fasting blood glucose was the variable that best predicted changes in glycosylated hemoglobin (45.5%). Meal frequency had no association with glycosylated hemoglobin. Meal frequency showed no association with metabolic control parameters in DM2 patients.

  15. PGC-1alpha Deficiency Causes Multi-System Energy Metabolic Derangements: Muscle Dysfunction, Abnormal Weight Control and Hepatic Steatosis

    Directory of Open Access Journals (Sweden)

    Leone Teresa C

    2005-01-01

    Full Text Available The gene encoding the transcriptional coactivator peroxisome proliferator-activated receptor-gamma coactivator-1alpha (PGC-1alpha was targeted in mice. PGC-1alpha null (PGC-1alpha-/- mice were viable. However, extensive phenotyping revealed multi-system abnormalities indicative of an abnormal energy metabolic phenotype. The postnatal growth of heart and slow-twitch skeletal muscle, organs with high mitochondrial energy demands, is blunted in PGC-1alpha-/- mice. With age, the PGC-1alpha-/- mice develop abnormally increased body fat, a phenotype that is more severe in females. Mitochondrial number and respiratory capacity is diminished in slow-twitch skeletal muscle of PGC-1alpha-/- mice, leading to reduced muscle performance and exercise capacity. PGC-1alpha-/- mice exhibit a modest diminution in cardiac function related largely to abnormal control of heart rate. The PGC-1alpha-/- mice were unable to maintain core body temperature following exposure to cold, consistent with an altered thermogenic response. Following short-term starvation, PGC-1alpha-/- mice develop hepatic steatosis due to a combination of reduced mitochondrial respiratory capacity and an increased expression of lipogenic genes. Surprisingly, PGC-1alpha-/- mice were less susceptible to diet-induced insulin resistance than wild-type controls. Lastly, vacuolar lesions were detected in the central nervous system of PGC-1alpha-/- mice. These results demonstrate that PGC-1alpha is necessary for appropriate adaptation to the metabolic and physiologic stressors of postnatal life.

  16. PGC-1alpha deficiency causes multi-system energy metabolic derangements: muscle dysfunction, abnormal weight control and hepatic steatosis.

    Directory of Open Access Journals (Sweden)

    Teresa C Leone

    2005-04-01

    Full Text Available The gene encoding the transcriptional coactivator peroxisome proliferator-activated receptor-gamma coactivator-1alpha (PGC-1alpha was targeted in mice. PGC-1alpha null (PGC-1alpha(-/- mice were viable. However, extensive phenotyping revealed multi-system abnormalities indicative of an abnormal energy metabolic phenotype. The postnatal growth of heart and slow-twitch skeletal muscle, organs with high mitochondrial energy demands, is blunted in PGC-1alpha(-/- mice. With age, the PGC-1alpha(-/- mice develop abnormally increased body fat, a phenotype that is more severe in females. Mitochondrial number and respiratory capacity is diminished in slow-twitch skeletal muscle of PGC-1alpha(-/- mice, leading to reduced muscle performance and exercise capacity. PGC-1alpha(-/- mice exhibit a modest diminution in cardiac function related largely to abnormal control of heart rate. The PGC-1alpha(-/- mice were unable to maintain core body temperature following exposure to cold, consistent with an altered thermogenic response. Following short-term starvation, PGC-1alpha(-/- mice develop hepatic steatosis due to a combination of reduced mitochondrial respiratory capacity and an increased expression of lipogenic genes. Surprisingly, PGC-1alpha(-/- mice were less susceptible to diet-induced insulin resistance than wild-type controls. Lastly, vacuolar lesions were detected in the central nervous system of PGC-1alpha(-/- mice. These results demonstrate that PGC-1alpha is necessary for appropriate adaptation to the metabolic and physiologic stressors of postnatal life.

  17. 13C Mrs Studies of the Control of Hepatic Glycogen Metabolism at High Magnetic Fields

    Science.gov (United States)

    Miller, Corin O.; Cao, Jin; Zhu, He; Chen, Li M.; Wilson, George; Kennan, Richard; Gore, John C.

    2017-06-01

    Introduction: Glycogen is the primary intracellular storage form of carbohydrates. In contrast to most tissues where stored glycogen can only supply the local tissue with energy, hepatic glycogen is mobilized and released into the blood to maintain appropriate circulating glucose levels, and is delivered to other tissues as glucose in response to energetic demands. Insulin and glucagon, two current targets of high interest in the pharmaceutical industry, are well known glucose-regulating hormones whose primary effect in liver is to modulate glycogen synthesis and breakdown. The purpose of these studies was to develop methods to measure glycogen metabolism in real time non-invasively both in isolated mouse livers, and in non-human primates (NHPs) using 13C MRS. Methods: Livers were harvested from C57/Bl6 mice and perfused with [1-13C] Glucose. To demonstrate the ability to measure acute changes in glycogen metabolism ex-vivo, fructose, glucagon, and insulin were administered to the liver ex-vivo. The C1 resonance of glycogen was measured in real time with 13C MRS using an 11.7T (500 MHz) NMR spectrometer. To demonstrate the translatability of this approach, NHPs (male rhesus monkeys) were studied in a 7 T Philips MRI using a partial volume 1H/13C imaging coil. NPHs were subjected to a variable IV infusion of [1-13C] glucose (to maintain blood glucose at 3-4x basal), along with a constant 1 mg/kg/min infusion of fructose. The C1 resonance of glycogen was again measured in real time with 13C MRS. To demonstrate the ability to measure changes in glycogen metabolism in vivo, animals received a glucagon infusion (1 μg/kg bolus followed by 40 ng/kg/min constant infusion) half way through the study on the second study session. Results: In both perfused mouse livers and in NHPs, hepatic 13C-glycogen synthesis (i.e. monotonic increases in the 13C-glycogen NMR signal) was readily detected. In both paradigms, addition of glucagon resulted in cessation of glycogen synthesis

  18. Bioenergy good practice

    Energy Technology Data Exchange (ETDEWEB)

    Birse, J.; Chambers, K.

    2000-07-01

    This report gives details of a project to make the Good Practice Guidelines, which were developed to help the UK Bioenergy industry, the national and local governments, and the public, more widely available. Details concerning the designing of a Good Practice Programme, and the proposed codes of Good Practice programme are given, and general relevant good practice guidance documents are discussed. The stakeholder survey and workshop, and the proposed codes of a Good Practice Programme are presented in Annexes. (UK)

  19. Randomised controlled trial: Effects of aerobic exercise training programme on indices of adiposity and metabolic markers in hypertension

    International Nuclear Information System (INIS)

    Lamina, S.; Okoye, C.G.

    2013-01-01

    Objective: To investigate the effects of interval training programme on blood pressure, maximal oxygen consumption, indices of adiposity and metabolic markers in black African men with essential hypertension. Methods: The study was conducted at Murtala Muhammed Specialist Hospital, Kano, Nigeria, from October 24, 2007 to February 24, 2009. It comprised 245 male patients with mild to moderate (systolic blood pressure 140-179 and diastolic blood pressure 90-109 mmHg) essential hypertension who were age-matched and grouped into experimental and control groups. The experimental group was involved in an 8-week training programme of between 45 and 60 minutes, while the controls remained sedentary during the period. Cardiovascular parameters, maximal oxygen consumption, per cent body fat, waist-to-hip ratio, body mass index, fasting blood sugar, total cholesterol, triglyceride, high density lipoprotein, low density lipoprotein and artherogenic index were assessed. Analysis of co-variance and Pearson correlation tests were used in data analysis which was done using SPSS 16. Results: The study had 140 (57.1%) cases with a mean age of 58.90+-7.35 years, and 105 (42.9%) controls with a mean age of 58.27+-6.24 years. It revealed significant increased effect of interval training programme on maximal oxygen consumption and high-density lipoprotein. There was significant reduction in on all the other controls. Changes in maximal oxygen consumption as a result of interval training significantly and negatively correlated with the other variables except high-density lipoprotein. Conclusions: The therapeutic role of interval exercise training on blood pressure reduction may be mediated through elevation of high-density lipoprotein, reduction of other markers of metabolism, and reduction in bodyweight and fatness. (author)

  20. Negative Affectivity Predicts Lower Quality of Life and Metabolic Control in Type 2 Diabetes Patients: A Structural Equation Modeling Approach

    Directory of Open Access Journals (Sweden)

    Chiara Conti

    2017-05-01

    Full Text Available Introduction: It is essential to consider the clinical assessment of psychological aspects in patients with Diabetes Mellitus (DM, in order to prevent potentially adverse self-management care behaviors leading to diabetes-related complications, including declining levels of Quality of Life (QoL and negative metabolic control.Purpose: In the framework of Structural Equation Modeling (SEM, the specific aim of this study is to evaluate the influence of distressed personality factors as Negative Affectivity (NA and Social Inhibition (SI on diabetes-related clinical variables (i.e., QoL and glycemic control.Methods: The total sample consists of a clinical sample, including 159 outpatients with Type 2 Diabetes Mellitus (T2DM, and a control group composed of 102 healthy respondents. All participants completed the following self- rating scales: The Type D Scale (DS14 and the World Health Organization QoL Scale (WHOQOLBREF. Furthermore, the participants of the clinical group were assessed for HbA1c, disease duration, and BMI. The observed covariates were BMI, gender, and disease duration, while HbA1c was considered an observed variable.Results: SEM analysis revealed significant differences between groups in regards to the latent construct of NA and the Environmental dimension of QoL. For the clinical sample, SEM showed that NA had a negative impact on both QoL dimensions and metabolic control.Conclusions: Clinical interventions aiming to improve medication adherence in patients with T2DM should include the psychological evaluation of Type D Personality traits, by focusing especially on its component of NA as a significant risk factor leading to negative health outcomes.

  1. Benefits of SGLT2 Inhibitors beyond glycemic control - A focus on metabolic, cardiovascular, and renal outcomes.

    Science.gov (United States)

    Minze, Molly G; Will, Kayley; Terrell, Brian T; Black, Robin L; Irons, Brian K

    2017-08-16

    Sodium-glucose co-transporter 2 (SGLT2) inhibitors are a new pharmacotherapeutic class for the treatment of type 2 diabetes mellitus (T2DM). To evaluate beneficial effects of the SGLT2 inhibitors on metabolic, cardiovascular, and renal outcomes. A Pub-Med search (1966 to July 2017) was performed of published English articles using keywords sodium-glucose co-transporter 2 inhibitors, canagliflozin, dapagliflozin, and empagliflozin. A review of literature citations provided further references. The search identified 17clinical trials and 2 meta-analysis with outcomes of weight loss and blood pressure reduction with dapagliflozin, canagliflozin, or empagliflozin. Three randomized trials focused on either empagliflozin or canagliflozin and reduction of cardiovascular disease and progression of renal disease. SGLT2 inhibitors have a beneficial profile in the treatment of T2DM. They have evidence of reducing weight between 2.9 kilograms when used as monotherapy to 4.7 kilograms when used in combination with metformin, and reduce systolic blood pressure between 3 to 5 mmHg and reduce diastolic blood pressure approximately 2 mmHg. To date, reduction of cardiovascular events was seen specifically with empagliflozin in patients with T2DM and a history of cardiovascular disease. In the same population, empagliflozin was associated with slowing the progression of kidney disease. Moreover, patients with increased risk of cardiovascular disease treated with canagliflozin has decreased risk of death from cardiovascular causes, nonfatal MI, or nonfatal stroke. Data regarding these outcomes with dapagliflozin are underway. SGLT2 inhibitors demonstrate some positive metabolic effects. In addition, empagliflozin specifically has demonstrated reduction in cardiovascular events and delay in the progression of kidney disease in patients with T2DM and a history of cardiovascular disease. Further data is needed to assess if this is a class effect. Copyright© Bentham Science Publishers

  2. Dissecting rice polyamine metabolism under controlled long-term drought stress.

    Directory of Open Access Journals (Sweden)

    Phuc Thi Do

    Full Text Available A selection of 21 rice cultivars (Oryza sativa L. ssp. indica and japonica was characterized under moderate long-term drought stress by comprehensive physiological analyses and determination of the contents of polyamines and selected metabolites directly related to polyamine metabolism. To investigate the potential regulation of polyamine biosynthesis at the transcriptional level, the expression of 21 genes encoding enzymes involved in these pathways were analyzed by qRT-PCR. Analysis of the genomic loci revealed that 11 of these genes were located in drought-related QTL regions, in agreement with a proposed role of polyamine metabolism in rice drought tolerance. The cultivars differed widely in their drought tolerance and parameters such as biomass and photosynthetic quantum yield were significantly affected by drought treatment. Under optimal irrigation free putrescine was the predominant polyamine followed by free spermidine and spermine. When exposed to drought putrescine levels decreased markedly and spermine became predominant in all cultivars. There were no correlations between polyamine contents and drought tolerance. GC-MS analysis revealed drought-induced changes of the levels of ornithine/arginine (substrate, substrates of polyamine synthesis, proline, product of a competing pathway and GABA, a potential degradation product. Gene expression analysis indicated that ADC-dependent polyamine biosynthesis responded much more strongly to drought than the ODC-dependent pathway. Nevertheless the fold change in transcript abundance of ODC1 under drought stress was linearly correlated with the drought tolerance of the cultivars. Combining metabolite and gene expression data, we propose a model of the coordinate adjustment of polyamine biosynthesis for the accumulation of spermine under drought conditions.

  3. [Metabolic Control, Evaluation and Follow-up Interventions in Patients With Schizophrenia].

    Science.gov (United States)

    Oviedo, Gabriel Fernando; Gómez Restrepo, Carlos; Bohórquez Peñaranda, Adriana; García Valencia, Jenny; Jaramillo, Luis Eduardo; Tamayo, Nathalie; Arenas, María Luisa; Vélez Fernández, Carolina

    2015-01-01

    To determine the laboratory tests, related to metabolic risk that should be practiced to adult patients diagnosed with schizophrenia. To assist the clinician decision-making process about complementary diagnostic evaluation strategies in adult diagnosed with schizophrenia. A clinical practice guideline was elaborated under the parameters of the Methodological Guide of the Ministerio de Salud y Protección Social to identify, synthesize and evaluate the evidence and make recommendations about the treatment and follow-up of adult patients with schizophrenia. The evidence of NICE guide 82 was adopted and updated. The evidence was presented to the Guideline Developing Group and recommendations, employing the GRADE system, were produced. The risk of overall mortality in schizophrenia is higher than in the general population excluding suicide. Results related with mortality associated to antipsychotics showed contradictory results. Metabolic outcomes showed a higher incidence and association with schizophrenia and treatment with antipsychotics (AP). The diagnosis of dyslipidemia in men with schizophrenia appears to be lower in comparison with the general population. However, changes in weight, blood sugar levels, HDL cholesterol and triglycerides are influenced by the use of antipsychotics in general there is a higher risk of developing diabetes mellitus in adults with schizophrenia. Based on the evidence found a plan was formulated for the evaluation of physiological and paraclinical variables during and before the management with AP in adult diagnosed with schizophrenia. The overall quality of evidence is low considering that most of the reports come from observational studies that have risk of bias and some designs have methodological limitations. Copyright © 2014 Asociación Colombiana de Psiquiatría. Publicado por Elsevier España. All rights reserved.

  4. Phase I to II cross-induction of xenobiotic metabolizing enzymes: A feedforward control mechanism for potential hormetic responses

    International Nuclear Information System (INIS)

    Zhang Qiang; Pi Jingbo; Woods, Courtney G.; Andersen, Melvin E.

    2009-01-01

    Hormetic responses to xenobiotic exposure likely occur as a result of overcompensation by the homeostatic control systems operating in biological organisms. However, the mechanisms underlying overcompensation that leads to hormesis are still unclear. A well-known homeostatic circuit in the cell is the gene induction network comprising phase I, II and III metabolizing enzymes, which are responsible for xenobiotic detoxification, and in many cases, bioactivation. By formulating a differential equation-based computational model, we investigated in this study whether hormesis can arise from the operation of this gene/enzyme network. The model consists of two feedback and one feedforward controls. With the phase I negative feedback control, xenobiotic X activates nuclear receptors to induce cytochrome P450 enzyme, which bioactivates X into a reactive metabolite X'. With the phase II negative feedback control, X' activates transcription factor Nrf2 to induce phase II enzymes such as glutathione S-transferase and glutamate cysteine ligase, etc., which participate in a set of reactions that lead to the metabolism of X' into a less toxic conjugate X''. The feedforward control involves phase I to II cross-induction, in which the parent chemical X can also induce phase II enzymes directly through the nuclear receptor and indirectly through transcriptionally upregulating Nrf2. As a result of the active feedforward control, a steady-state hormetic relationship readily arises between the concentrations of the reactive metabolite X' and the extracellular parent chemical X to which the cell is exposed. The shape of dose-response evolves over time from initially monotonically increasing to J-shaped at the final steady state-a temporal sequence consistent with adaptation-mediated hormesis. The magnitude of the hormetic response is enhanced by increases in the feedforward gain, but attenuated by increases in the bioactivation or phase II feedback loop gains. Our study suggests a

  5. Phase I to II cross-induction of xenobiotic metabolizing enzymes: a feedforward control mechanism for potential hormetic responses.

    Science.gov (United States)

    Zhang, Qiang; Pi, Jingbo; Woods, Courtney G; Andersen, Melvin E

    2009-06-15

    Hormetic responses to xenobiotic exposure likely occur as a result of overcompensation by the homeostatic control systems operating in biological organisms. However, the mechanisms underlying overcompensation that leads to hormesis are still unclear. A well-known homeostatic circuit in the cell is the gene induction network comprising phase I, II and III metabolizing enzymes, which are responsible for xenobiotic detoxification, and in many cases, bioactivation. By formulating a differential equation-based computational model, we investigated in this study whether hormesis can arise from the operation of this gene/enzyme network. The model consists of two feedback and one feedforward controls. With the phase I negative feedback control, xenobiotic X activates nuclear receptors to induce cytochrome P450 enzyme, which bioactivates X into a reactive metabolite X'. With the phase II negative feedback control, X' activates transcription factor Nrf2 to induce phase II enzymes such as glutathione S-transferase and glutamate cysteine ligase, etc., which participate in a set of reactions that lead to the metabolism of X' into a less toxic conjugate X''. The feedforward control involves phase I to II cross-induction, in which the parent chemical X can also induce phase II enzymes directly through the nuclear receptor and indirectly through transcriptionally upregulating Nrf2. As a result of the active feedforward control, a steady-state hormetic relationship readily arises between the concentrations of the reactive metabolite X' and the extracellular parent chemical X to which the cell is exposed. The shape of dose-response evolves over time from initially monotonically increasing to J-shaped at the final steady state-a temporal sequence consistent with adaptation-mediated hormesis. The magnitude of the hormetic response is enhanced by increases in the feedforward gain, but attenuated by increases in the bioactivation or phase II feedback loop gains. Our study suggests a

  6. Metabolic syndrome in patients with bipolar disorder: comparison with major depressive disorder and non-psychiatric controls.

    Science.gov (United States)

    Silarova, Barbora; Giltay, Erik J; Van Reedt Dortland, Arianne; Van Rossum, Elisabeth F C; Hoencamp, Erik; Penninx, Brenda W J H; Spijker, Annet T

    2015-04-01

    We aimed to investigate the prevalence of the metabolic syndrome (MetS) and its individual components in subjects with bipolar disorder (BD) compared to those with major depressive disorder (MDD) and non-psychiatric controls. We examined 2431 participants (mean age 44.3±13.0, 66.1% female), of whom 241 had BD; 1648 had MDD; and 542 were non-psychiatric controls. The MetS was ascertained according to NCEP ATP III criteria. Multivariable analyses were adjusted for age, sex, ethnicity, level of education, smoking status and severity of depressive symptoms, and in the case of BD subjects, also for psychotropic medication use. Subjects with BD had a significantly higher prevalence of MetS when compared to subjects with MDD and non-psychiatric controls (28.4% vs. 20.2% and 16.5%, respectively, pdifferences between BD subjects with controls could partly be ascribed to a higher mean waist circumference (91.0 cm vs. 88.8, respectively, p=0.03). In stratified analysis, the differences in the prevalence of MetS between patients with BD and MDD were found in symptomatic but not in asymptomatic cases. This study confirms a higher prevalence of MetS in patients with BD compared to both MDD patients and controls. Specifically at risk are patients with a higher depression score and abdominal obesity. Copyright © 2015 Elsevier Inc. All rights reserved.

  7. Treatment of metabolic syndrome by combination of physical activity and diet needs an optimal protein intake: a randomized controlled trial.

    Science.gov (United States)

    Dutheil, Frédéric; Lac, Gérard; Courteix, Daniel; Doré, Eric; Chapier, Robert; Roszyk, Laurence; Sapin, Vincent; Lesourd, Bruno

    2012-09-17

    The recommended dietary allowance (RDA) for protein intake has been set at 1.0-1.3 g/kg/day for senior. To date, no consensus exists on the lower threshold intake (LTI = RDA/1.3) for the protein intake (PI) needed in senior patients ongoing both combined caloric restriction and physical activity treatment for metabolic syndrome. Considering that age, caloric restriction and exercise are three increasing factors of protein need, this study was dedicated to determine the minimal PI in this situation, through the determination of albuminemia that is the blood marker of protein homeostasis. Twenty eight subjects (19 M, 9 F, 61.8 ± 6.5 years, BMI 33.4 ± 4.1 kg/m²) with metabolic syndrome completed a three-week residential programme (Day 0 to Day 21) controlled for nutrition (energy balance of -500 kcal/day) and physical activity (3.5 hours/day). Patients were randomly assigned in two groups: Normal-PI (NPI: 1.0 g/kg/day) and High-PI (HPI: 1.2 g/kg/day). Then, patients returned home and were followed for six months. Albuminemia was measured at D0, D21, D90 and D180. At baseline, PI was spontaneously 1.0 g/kg/day for both groups. Albuminemia was 40.6 g/l for NPI and 40.8 g/l for HPI. A marginal protein under-nutrition appeared in NPI with a decreased albuminemia at D90 below 35 g/l (34.3 versus 41.5 g/l for HPI, p treatment based on restricted diet and exercise in senior people with metabolic syndrome, the lower threshold intake for protein must be set at 1.2 g/kg/day to maintain blood protein homeostasis.

  8. Metabolomics reveals the metabolic shifts following an intervention with rye bread in postmenopausal women- a randomized control trial

    Directory of Open Access Journals (Sweden)

    Moazzami Ali A

    2012-10-01

    Full Text Available Abstract Background Epidemiological studies have consistently shown that whole grain (WG cereals can protect against the development of chronic diseases, but the underlying mechanism is not fully understood. Among WG products, WG rye is considered even more potent because of its unique discrepancy in postprandial insulin and glucose responses known as the rye factor. In this study, an NMR-based metabolomics approach was applied to study the metabolic effects of WG rye as a tool to determine the beneficial effects of WG rye on human health. Methods Thirty-three postmenopausal Finnish women with elevated serum total cholesterol (5.0-8.5 mmol/L and BMI of 20–33 kg/m2 consumed a minimum of 20% of their daily energy intake as high fiber WG rye bread (RB or refined wheat bread (WB in a randomized, controlled, crossover design with two 8-wk intervention periods separated by an 8-wk washout period. At the end of each intervention period, fasting serum was collected for NMR-based metabolomics and the analysis of cholesterol fractions. Multilevel partial least squares discriminant analysis was used for paired comparisons of multivariate data. Results The metabolomics analysis of serum showed lower leucine and isoleucine and higher betaine and N,N-dimethylglycine levels after RB than WB intake. To further investigate the metabolic effects of RB, the serum cholesterol fractions were measured. Total- and LDL-cholesterol levels were higher after RB intake than after WB (p Conclusions This study revealed favorable shifts in branched amino acid and single carbon metabolism and an unfavorable shift in serum cholesterol levels after RB intake in postmenopausal women, which should be considered for evaluating health beneficial effects of rye products.

  9. Effects of testosterone treatment on glucose metabolism and symptoms in men with type 2 diabetes and the metabolic syndrome: a systematic review and meta-analysis of randomized controlled clinical trials.

    Science.gov (United States)

    Grossmann, Mathis; Hoermann, Rudolf; Wittert, Gary; Yeap, Bu B

    2015-09-01

    The effects of testosterone treatment on glucose metabolism and other outcomes in men with type 2 diabetes (T2D) and/or the metabolic syndrome are controversial. To perform a systematic review and meta-analysis of placebo-controlled double-blind randomized controlled clinical trials (RCT) of testosterone treatment in men with T2D and/or the metabolic syndrome. A systematic search of RCTs was conducted using Medline, Embase and the Cochrane Register of controlled trials from inception to July 2014 followed by a manual review of the literature. Eligible studies were published placebo-controlled double-blind RCTs published in English. Two reviewers independently selected studies, determined study quality and extracted outcome and descriptive data. Of the 112 identified studies, seven RCTs including 833 men were eligible for the meta-analysis. In studies using a simple linear equation to calculate the homeostatic model assessment of insulin resistance (HOMA1), testosterone treatment modestly improved insulin resistance, compared to placebo, pooled mean difference (MD) -1·58 [-2·25, -0·91], P treatment effect was nonsignificant for RCTs using a more stringent computer-based equation (HOMA2), MD -0·19 [-0·86, 0·49], P = 0·58). Testosterone treatment did not improve glycaemic (HbA1c) control, MD -0·15 [-0·39, 0·10], P = 0·25, or constitutional symptoms, Aging Male Symptom score, MD -2·49 [-5·81, 0·83], P = 0·14). This meta-analysis does not support the routine use of testosterone treatment in men with T2D and/or the metabolic syndrome without classical hypogonadism. Additional studies are needed to determine whether hormonal interventions are warranted in selected men with T2D and/or the metabolic syndrome. © 2014 John Wiley & Sons Ltd.

  10. Clinical study on the prevalence and comparative analysis of metabolic syndrome and its components among Chinese breast cancer women and control population.

    Science.gov (United States)

    Wu, Yu-Tuan; Luo, Qing-Qing; Li, Xin; Arshad, Bilal; Xu, Zhou; Ran, Liang; Zhao, Chun-Xia; Wu, He; Shi, Yan-Ling; Chen, Hao-Ran; Li, Hao; Li, Hong-Yuan; Wu, Kai-Nan; Kong, Ling-Quan

    2018-01-01

    Metabolic syndrome has been previously identified as a risk factor for breast cancer and is increasingly a public health concern. This study aims to investigate the prevalence of metabolic syndrome and its components among primary breast cancer and control population. The clinical data of metabolic syndrome and its components in the breast cancer (605 cases) and control population (3212 cases), from Breast Cancer Center and Physical Examination Center of Chongqing, China, from July 2015 to February 2017, were collected for comparative analysis. This study was prospectively registered in Chinese Clinical Trial Registry (http://www.chictr.org.cn/, number: ChiCTR-OOB-15007543). The prevalence of metabolic syndrome in breast cancer (32.6%) was obviously higher than that in control population (18.2%) (pmetabolic syndrome in breast cancer group aged below 60 years (24.9%, pmetabolic syndrome and its components in Chinese breast cancer women, and metabolic syndrome is closely related with breast cancer. Therefore, screening and prevention strategy of metabolic syndrome should be carried out in the management of breast cancer.

  11. Association of neural tube defects in children of mothers with MTHFR 677TT genotype and abnormal carbohydrate metabolism risk: a case-control study.

    Science.gov (United States)

    Cadenas-Benitez, N M; Yanes-Sosa, F; Gonzalez-Meneses, A; Cerrillos, L; Acosta, D; Praena-Fernandez, J M; Neth, O; Gomez de Terreros, I; Ybot-González, P

    2014-03-26

    Abnormalities in maternal folate and carbohydrate metabolism have both been shown to induce neural tube defects (NTD) in humans and animal models. However, the relationship between these two factors in the development of NTDs remains unclear. Data from mothers of children with spina bifida seen at the Unidad de Espina Bífida del Hospital Infantil Virgen del Rocío (case group) were compared to mothers of healthy children with no NTD (control group) who were randomly selected from patients seen at the outpatient ward in the same hospital. There were 25 individuals in the case group and 41 in the control group. Analysis of genotypes for the methylenetetrahydrofolate reductase (MTHFR) 677CT polymorphism in women with or without risk factors for abnormal carbohydrate metabolism revealed that mothers who were homozygous for the MTHFR 677TT polymorphism and at risk of abnormal carbohydrate metabolism were more likely to have offspring with spina bifida and high levels of homocysteine, compared to the control group. The increased incidence of NTDs in mothers homozygous for the MTHFR 677TT polymorphism and at risk of abnormal carbohydrate metabolism stresses the need for careful metabolic screening in pregnant women, and, if necessary, determination of the MTHFR 677CT genotype in those mothers at risk of developing abnormal carbohydrate metabolism.

  12. [An analysis of the diabetic population in a Spanish rural are: morbidity profile, use of resources, complications and metabolic control].

    Science.gov (United States)

    Inoriza, José M; Pérez, Marc; Cols, Montse; Sánchez, Inma; Carreras, Marc; Coderch, Jordi

    2013-11-01

    To describe the characteristics of a diabetic population, morbidity profile, resource consumption, complications and degree of metabolic control. Cross-sectional study during 2010. Four Health Areas (91.301 people) where the integrated management organization Serveis de Salut integrated Baix Empordà completely provide healthcare assistance. 4.985 diabetic individuals, identified through clinical codes using the ICD-9-MC classification and the 3M? Clinical Risk Groups software. Morbidity profile, related complications and degree of metabolic control were obtained for the target diabetic population. We analyzed the consumption of healthcare resources, pharmaceutical and blood glucose reagent strips. All measurements obtained at individual level. 99.3% of the diabetic population were attended at least once at a primary care center (14.9% of visits). 39.5% of primary care visits and less than 10% of the other scanned resources were related to the management of diabetes. The pharmaceutical expenditure was 25.4% of the population consumption (average cost ?1.014,57). 36.5% of diabetics consumed reagents strips (average cost ?120,65). The more frequent CRG are 5424-Diabetes (27%); 6144-Diabetes and Hypertension (25,5%) and 6143-Diabetes and Other Moderate Chronic Disease (17,2%). The degree of disease control is better in patients not consumers of antidiabetic drugs or treated with oral antidiabetic agents not secretagogues. Comorbidity is decisive in the consumption of resources. Just a few part of this consumption is specifically related to the management of diabetes. Results obtained provide a whole population approach to the main existing studies in our national and regional context. Copyright © 2012 Elsevier España, S.L. All rights reserved.

  13. Combined treatment with melatonin and insulin improves glycemic control, white adipose tissue metabolism and reproductive axis of diabetic male rats.

    Science.gov (United States)

    Oliveira, Ariclecio Cunha de; Andreotti, Sandra; Sertie, Rogério António Laurato; Campana, Amanda Baron; de Proença, André Ricardo Gomes; Vasconcelos, Renata Prado; Oliveira, Keciany Alves de; Coelho-de-Souza, Andrelina Noronha; Donato-Junior, José; Lima, Fábio Bessa

    2018-04-15

    Melatonin treatment has been reported to be capable of ameliorating metabolic diabetes-related abnormalities but also to cause hypogonadism in rats. We investigated whether the combined treatment with melatonin and insulin can improve insulin resistance and other metabolic disorders in rats with streptozotocin-induced diabetes during neonatal period and the repercussion of this treatment on the hypothalamic-pituitary-gonadal axis. At the fourth week of age, diabetic animals started an 8-wk treatment with only melatonin (0.2 mg/kg body weight) added to drinking water at night or associated with insulin (NHP, 1.5 U/100 g/day) or only insulin. Animals were then euthanized, and the subcutaneous (SC), epididymal (EP), and retroperitoneal (RP) fat pads were excised, weighed and processed for adipocyte isolation for morphometric analysis as well as for measuring glucose uptake, oxidation, and incorporation of glucose into lipids. Hypothalamus was collected for gene expression and blood samples were collected for biochemical assays. The treatment with melatonin plus insulin (MI) was capable of maintaining glycemic control. In epididymal (EP) and subcutaneous (SC) adipocytes, the melatonin plus insulin (MI) treatment group recovered the insulin responsiveness. In the hypothalamus, melatonin treatment alone promoted a significant reduction in kisspeptin-1, neurokinin B and androgen receptor mRNA levels, in relation to control group. Combined treatment with melatonin and insulin promoted a better glycemic control, improving insulin sensitivity in white adipose tissue (WAT). Indeed, melatonin treatment reduced hypothalamic genes related to reproductive function. Copyright © 2017. Published by Elsevier Inc.

  14. Software licenses: Good fences make good neighbors

    International Nuclear Information System (INIS)

    McCreary, J.G.; Woodyard, A.

    1995-01-01

    The basis for a good contract is that it is beneficial to both parties. A good foundation will cement the responsibilities and obligations of the parties after areas of agreement have been negotiated. Unfortunately, software licenses do not always reflect what is best for all. Some clauses are definitely for the benefit of the vendor, while others are required by a prudent client. The resulting contract is then a matter of reasonable compromise to achieve a good business relationship. Major issues of warranty, liability, training, support, and payment may be in conflict. Such topics as maintenance, testing, patents, extent of use, and return of software are often overlooked or addressed unevenly. This paper addresses these subjects and provides guidelines for software licenses. An understanding of legal phrases is of value. A better understanding of the viewpoints of both the vendor and the client results in a better working relationship

  15. Prevalence and characteristics of metabolic syndrome in adults from the French childhood leukemia survivors’ cohort: a comparison with controls from the French population

    Science.gov (United States)

    Oudin, Claire; Berbis, Julie; Bertrand, Yves; Vercasson, Camille; Thomas, Frédérique; Chastagner, Pascal; Ducassou, Stéphane; Kanold, Justyna; Tabone, Marie-Dominique; Paillard, Catherine; Poirée, Marilyne; Plantaz, Dominique; Dalle, Jean-Hugues; Gandemer, Virginie; Thouvenin, Sandrine; Sirvent, Nicolas; Saultier, Paul; Béliard, Sophie; Leverger, Guy; Baruchel, André; Auquier, Pascal; Pannier, Bruno; Michel, Gérard

    2018-01-01

    The prevalence of the metabolic syndrome among adults from the French LEA childhood acute leukemia survivors’ cohort was prospectively evaluated considering the type of anti-leukemic treatment received, and compared with that of controls. The metabolic profile of these patients was compared with that of controls. A total of 3203 patients from a French volunteer cohort were age- and sex-matched 3:1 to 1025 leukemia survivors (in both cohorts, mean age: 24.4 years; females: 51%). Metabolic syndrome was defined according to the National Cholesterol Education Program’s Adult Treatment Panel III criteria. Metabolic syndrome was found in 10.3% of patients (mean follow-up duration: 16.3±0.2 years) and 4.5% of controls, (OR=2.49; Pmetabolic syndrome displayed a unique profile compared with controls: smaller waist circumference (91 vs. 99.6 cm; P=0.01), and increased triglyceride levels (3.99 vs. 1.5 mmol/L; Pmetabolic syndrome had a larger waist circumference (109 vs. 99.6 cm; P=0.007) than controls. Regardless of the anti-leukemic treatment, metabolic syndrome risk was higher among childhood leukemia survivors. Its presentation differed depending on the treatment type, thus suggesting a divergent pathophysiology. This study is registered at clinicaltrials.gov identifier: 01756599. PMID:29351982

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

    Science.gov (United States)

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

    2011-12-01

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

  17. A qualitative study of young people's perspectives of living with type 1 diabetes: do perceptions vary by levels of metabolic control?

    Science.gov (United States)

    Scholes, Cheryl; Mandleco, Barbara; Roper, Susanne; Dearing, Karen; Dyches, Tina; Freeborn, Donna

    2013-06-01

    To explore if young people with higher and lower levels of metabolic control of type 1 diabetes have different perceptions about their lives and illness. Adolescence through emerging adulthood is a developmental stage made more challenging when the person has type 1 diabetes. Little research has investigated if individuals with high and low levels of metabolic control in this age group perceive their disease differently. Qualitative descriptive. In this study, 14 participants, ages 11-22 years were interviewed in 2008 about their perceptions of living with type 1 diabetes. Through a process of induction, major themes were identified. Participants with high and low metabolic control levels reported similar themes related to reactions of others, knowledge about type 1 diabetes, and believed healthcare providers used authoritarian interactions. However, high metabolic control level participants believed type 1 diabetes would be cured; had negative initial responses to being diagnosed; rarely received parental support in managing their diabetes; and were negligent in self-care activities. Participants with low metabolic control levels did not believe a cure was imminent or have negative responses to being diagnosed; received parental support in managing diabetes; and were diligent in self-care activities. Nurses should give information to young people with type 1 diabetes beyond initial diagnosis and help and support this age group learn appropriate ways to manage their disease, develop positive relationships with healthcare professionals, and participate in interactions with others their age successfully managing type 1 diabetes. © 2012 Blackwell Publishing Ltd.

  18. Analysis of the impact of environmental and social factors, with a particular emphasis on education, on the level of metabolic control in type 1 diabetes in children.

    Science.gov (United States)

    Stefanowicz, Anna; Birkholz, Dorota; Myśliwiec, Małgorzata; Niedźwiecki, Maciej; Owczuk, Radosław; Balcerska, Anna

    2012-01-01

    Type 1 diabetes is a chronic, incurable childhood disease. Chronically uncontrolled diabetes is associated with eye, kidney, nerve, heart and blood vessel damage and function impairment. The aim of this study was to evaluate the impact of various social and environmental factors, with a particular emphasis on education, on the level of metabolic control in diabetes. The survey research was conducted in 102 children aged 0-18 years, diagnosed with type 1 diabetes. Based on the HbA(1c ) level, patients were divided into: group A (63 patients with fairly well and moderately controlled type 1 diabetes mellitus) and group B (39 patients with metabolically uncontrolled type 1 diabetes mellitus). The impact of various environmental and social factors on the degree of metabolic control of type 1 diabetes was analysed. No effect of typical environmental and social factors, such as: place of residence, gender, parents' education and their professional activity, on the level of metabolic control of type 1 diabetes was found. However, groups A and B significantly differed in the level of knowledge about diabetes and its treatment, in the regularity of meals, in possessing a nutrition scale and in the self-assessed preparation for taking care and custody of a child with type 1 diabetes. 1. Children with type 1 diabetes and their parents require ongoing education about the disease and its treatment. 2. The regularity of meals and the use of a nutrition scale have considerable impact on the level of metabolic control of the disease.

  19. Iron Sulfur and Molybdenum Cofactor Enzymes Regulate the Drosophila Life Cycle by Controlling Cell Metabolism

    Science.gov (United States)

    Marelja, Zvonimir; Leimkühler, Silke; Missirlis, Fanis

    2018-01-01

    Iron sulfur (Fe-S) clusters and the molybdenum cofactor (Moco) are present at enzyme sites, where the active metal facilitates electron transfer. Such enzyme systems are soluble in the mitochondrial matrix, cytosol and nucleus, or embedded in the inner mitochondrial membrane, but virtually absent from the cell secretory pathway. They are of ancient evolutionary origin supporting respiration, DNA replication, transcription, translation, the biosynthesis of steroids, heme, catabolism of purines, hydroxylation of xenobiotics, and cellular sulfur metabolism. Here, Fe-S cluster and Moco biosynthesis in Drosophila melanogaster is reviewed and the multiple biochemical and physiological functions of known Fe-S and Moco enzymes are described. We show that RNA interference of Mocs3 disrupts Moco biosynthesis and the circadian clock. Fe-S-dependent mitochondrial respiration is discussed in the context of germ line and somatic development, stem cell differentiation and aging. The subcellular compartmentalization of the Fe-S and Moco assembly machinery components and their connections to iron sensing mechanisms and intermediary metabolism are emphasized. A biochemically active Fe-S core complex of heterologously expressed fly Nfs1, Isd11, IscU, and human frataxin is presented. Based on the recent demonstration that copper displaces the Fe-S cluster of yeast and human ferredoxin, an explanation for why high dietary copper leads to cytoplasmic iron deficiency in flies is proposed. Another proposal that exosomes contribute to the transport of xanthine dehydrogenase from peripheral tissues to the eye pigment cells is put forward, where the Vps16a subunit of the HOPS complex may have a specialized role in concentrating this enzyme within pigment granules. Finally, we formulate a hypothesis that (i) mitochondrial superoxide mobilizes iron from the Fe-S clusters in aconitase and succinate dehydrogenase; (ii) increased iron transiently displaces manganese on superoxide dismutase, which

  20. Iron Sulfur and Molybdenum Cofactor Enzymes Regulate the Drosophila Life Cycle by Controlling Cell Metabolism

    Directory of Open Access Journals (Sweden)

    Zvonimir Marelja

    2018-02-01

    Full Text Available Iron sulfur (Fe-S clusters and the molybdenum cofactor (Moco are present at enzyme sites, where the active metal facilitates electron transfer. Such enzyme systems are soluble in the mitochondrial matrix, cytosol and nucleus, or embedded in the inner mitochondrial membrane, but virtually absent from the cell secretory pathway. They are of ancient evolutionary origin supporting respiration, DNA replication, transcription, translation, the biosynthesis of steroids, heme, catabolism of purines, hydroxylation of xenobiotics, and cellular sulfur metabolism. Here, Fe-S cluster and Moco biosynthesis in Drosophila melanogaster is reviewed and the multiple biochemical and physiological functions of known Fe-S and Moco enzymes are described. We show that RNA interference of Mocs3 disrupts Moco biosynthesis and the circadian clock. Fe-S-dependent mitochondrial respiration is discussed in the context of germ line and somatic development, stem cell differentiation and aging. The subcellular compartmentalization of the Fe-S and Moco assembly machinery components and their connections to iron sensing mechanisms and intermediary metabolism are emphasized. A biochemically active Fe-S core complex of heterologously expressed fly Nfs1, Isd11, IscU, and human frataxin is presented. Based on the recent demonstration that copper displaces the Fe-S cluster of yeast and human ferredoxin, an explanation for why high dietary copper leads to cytoplasmic iron deficiency in flies is proposed. Another proposal that exosomes contribute to the transport of xanthine dehydrogenase from peripheral tissues to the eye pigment cells is put forward, where the Vps16a subunit of the HOPS complex may have a specialized role in concentrating this enzyme within pigment granules. Finally, we formulate a hypothesis that (i mitochondrial superoxide mobilizes iron from the Fe-S clusters in aconitase and succinate dehydrogenase; (ii increased iron transiently displaces manganese on superoxide

  1. Growth Patterns in the Irish Pyridoxine Nonresponsive Homocystinuria Population and the Influence of Metabolic Control and Protein Intake.

    Science.gov (United States)

    Purcell, Orla; Coughlan, Aoife; Grant, Tim; McNulty, Jenny; Clark, Anne; Deverell, Deirdre; Mayne, Philip; Hughes, Joanne; Monavari, Ahmad; Knerr, Ina; Crushell, Ellen

    2017-01-01

    A low methionine diet is the mainstay of treatment for pyridoxine nonresponsive homocystinuria (HCU). There are various guidelines for recommended protein intakes for HCU and clinical practice varies. Poor growth has been associated with low cystine levels. This retrospective review of 48 Irish pyridoxine nonresponsive HCU patients assessed weight, height, body mass index (BMI), protein intake, and metabolic control up to 18 years at nine set time points. Patients diagnosed through newborn screening (NBS) were compared to late diagnosed (LD) patients. At 18 years the LD group ( n = 12, mean age at diagnosis 5.09 years) were heavier (estimated effect +4.97 Kg, P = 0.0058) and taller (estimated effect +7.97 cm P = 0.0204) than the NBS group ( n = 36). There was no difference in growth rate between the groups after 10 years of age. The HCU population were heavier and taller than the general population by one standard deviation with no difference in BMI. There was no association between intermittently low cystine levels and height. Three protein intake guidelines were compared; there was no difference in adult height between those who met the lowest of the guidelines (Genetic Metabolic Dietitians International) and those with a higher protein intake.

  2. Control of Secreted Protein Gene Expression and the Mammalian Secretome by the Metabolic Regulator PGC-1α.

    Science.gov (United States)

    Minsky, Neri; Roeder, Robert G

    2017-01-06

    Secreted proteins serve pivotal roles in the development of multicellular organisms, acting as structural matrix, extracellular enzymes, and signal molecules. However, how the secretome is regulated remains incompletely understood. Here we demonstrate, unexpectedly, that peroxisome proliferator-activated receptor γ coactivator 1-α (PGC-1α), a critical transcriptional co-activator of metabolic gene expression, functions to down-regulate the expression of diverse genes encoding secreted molecules and extracellular matrix components to modulate the secretome. Using cell lines, primary cells, and mice, we show that both endogenous and exogenous PGC-1α down-regulate the expression of numerous genes encoding secreted molecules. Mechanistically, results obtained using mRNA stability measurements as well as intronic RNA expression analysis are consistent with a transcriptional effect of PGC-1α on the expression of genes encoding secreted proteins. Interestingly, PGC-1α requires the central heat shock response regulator heat shock factor protein 1 (HSF1) to affect some of its targets, and both factors co-reside on several target genes encoding secreted molecules in cells. Finally, using a mass spectrometric analysis of secreted proteins, we demonstrate that PGC-1α modulates the secretome of mouse embryonic fibroblasts. Our results define a link between a key pathway controlling metabolic regulation and the regulation of the mammalian secretome. © 2017 by The American Society for Biochemistry and Molecular Biology, Inc.

  3. The Impact of a Cultural Lifestyle Intervention on Metabolic Parameters After Gestational Diabetes Mellitus A Randomized Controlled Trial.

    Science.gov (United States)

    Zilberman-Kravits, Dana; Meyerstein, Naomi; Abu-Rabia, Yones; Wiznitzer, Arnon; Harman-Boehm, Ilana

    2018-06-01

    The prevalence of type 2 diabetes in Israel is increasing in all ethnic groups but most markedly in the Bedouin population. We aimed to assess the effects of a lifestyle change intervention on risk markers for type 2 diabetes after gestational diabetes mellitus (GDM). One hundred eighty Jewish and Bedouin post-GDM women were randomly assigned to a lifestyle intervention group (IG) or a control group (CG) starting 3-4 months after delivery. The IG participated in healthy lifestyle sessions led by a dietician and a sports instructor for 24 months after delivery. The IG participants had three individual 45-min counseling sessions and four 90-min group meetings (10 women each). The dietary and exercise recommendations were culturally adapted. The primary outcome of the study was HOMA-IR. We monitored clinical and chemical biomarkers 1 and 2 years after delivery. After 1 and 2 years of intervention, the metabolic measures improved substantially. The intervention reduced the insulin, glucose and HOMA-IR levels in the IG compared with those in the CG (p < 0.001). This novel culturally tailored lifestyle intervention program significantly improved the metabolic and morphometric indices measured 1 and 2 years after delivery. These results highlight and underscore the importance of effective lifestyle change education following GDM.

  4. Growth Patterns in the Irish Pyridoxine Nonresponsive Homocystinuria Population and the Influence of Metabolic Control and Protein Intake

    Directory of Open Access Journals (Sweden)

    Orla Purcell

    2017-01-01

    Full Text Available A low methionine diet is the mainstay of treatment for pyridoxine nonresponsive homocystinuria (HCU. There are various guidelines for recommended protein intakes for HCU and clinical practice varies. Poor growth has been associated with low cystine levels. This retrospective review of 48 Irish pyridoxine nonresponsive HCU patients assessed weight, height, body mass index (BMI, protein intake, and metabolic control up to 18 years at nine set time points. Patients diagnosed through newborn screening (NBS were compared to late diagnosed (LD patients. At 18 years the LD group (n=12, mean age at diagnosis 5.09 years were heavier (estimated effect +4.97 Kg, P=0.0058 and taller (estimated effect +7.97 cm P=0.0204 than the NBS group (n=36. There was no difference in growth rate between the groups after 10 years of age. The HCU population were heavier and taller than the general population by one standard deviation with no difference in BMI. There was no association between intermittently low cystine levels and height. Three protein intake guidelines were compared; there was no difference in adult height between those who met the lowest of the guidelines (Genetic Metabolic Dietitians International and those with a higher protein intake.

  5. Control of seizures by ketogenic diet-induced modulation of metabolic pathways.

    Science.gov (United States)

    Clanton, Ryan M; Wu, Guoyao; Akabani, Gamal; Aramayo, Rodolfo

    2017-01-01

    Epilepsy is too complex to be considered as a disease; it is more of a syndrome, characterized by seizures, which can be caused by a diverse array of afflictions. As such, drug interventions that target a single biological pathway will only help the specific individuals where that drug's mechanism of action is relevant to their disorder. Most likely, this will not alleviate all forms of epilepsy nor the potential biological pathways causing the seizures, such as glucose/amino acid transport, mitochondrial dysfunction, or neuronal myelination. Considering our current inability to test every individual effectively for the true causes of their epilepsy and the alarming number of misdiagnoses observed, we propose the use of the ketogenic diet (KD) as an effective and efficient preliminary/long-term treatment. The KD mimics fasting by altering substrate metabolism from carbohydrates to fatty acids and ketone bodies (KBs). Here, we underscore the need to understand the underlying cellular mechanisms governing the KD's modulation of various forms of epilepsy and how a diverse array of metabolites including soluble fibers, specific fatty acids, and functional amino acids (e.g., leucine, D-serine, glycine, arginine metabolites, and N-acetyl-cysteine) may potentially enhance the KD's ability to treat and reverse, not mask, these neurological disorders that lead to epilepsy.

  6. Arcuate NPY neurons sense and integrate peripheral metabolic signals to control feeding.

    Science.gov (United States)

    Kohno, Daisuke; Yada, Toshihiko

    2012-12-01

    NPY neuron in the hypothalamic arcuate nucleus is a key feeding center. Studies have shown that NPY neuron in the arcuate nucleus has a role to induce food intake. The arcuate nucleus is structurally unique with lacking blood brain barrier. Peripheral energy signals including hormones and nutrition can reach the arcuate nucleus. In this review, we discuss sensing and integrating peripheral signals in NPY neurons. In the arcuate nucleus, ghrelin mainly activates NPY neurons. Leptin and insulin suppress the ghrelin-induced activation in 30-40% of the ghrelin-activated NPY neurons. Lowering glucose concentration activates 40% of NPY neurons. These results indicate that NPY neuron in the arcuate nucleus is a feeding center in which major peripheral energy signals are directly sensed and integrated. Furthermore, there are subpopulations of NPY neurons in regard to their responsiveness to peripheral signals. These findings suggest that NPY neuron in the arcuate nucleus is an essential feeding center to induce food intake in response to peripheral metabolic state. Copyright © 2012 Elsevier Ltd. All rights reserved.

  7. Metabolic effect of Gum Arabic (Acacia Senegal in patients with Type 2 Diabetes Mellitus (T2DM: Randomized, placebo controlled double blind trial

    Directory of Open Access Journals (Sweden)

    Rasha Babiker

    2017-03-01

    Full Text Available Background:Gum Arabic (GA is a water-soluble dietary fiber, indigestible to both humans and animals. While GAcurrently does not have any therapeutic potential, ithas nutritional value andsome effects on metabolism of glucose and lipids. Thus, theaim of this study is to assess the effect of GA on serum level of glucose, lipids,and the BMI in type 2 diabetic patients.Methods:A double-blind randomizedplacebo-controlled trial took placeat Academy Charity Teaching Hospital (ACTH in Sudan between August 2014 to February 2015. The trial was conducted intype 2 diabetic patients who were on regular oral hypoglycemicdrugs andhad HbA1C ≥ 6.5%. Patients excluded from the study included those on insulin, any patient with a metabolic or gastrointestinal disease,and any patient with history of drug addiction and alcoholism. Other patients excluded were patients who had previous allergic reactionsto GA in addition topatients who were pregnant or plannedfor conception within 6 months. 120 patients were invited to participate in this trial. 100 patients gave consent and wererandomizedto GA and placebo groups. The GA group was given 30 g of Acacia Senegaland the placebo group was given 5 g of placebodaily for 3 months. The outcomesassessedwereprimarily the effect of GA on glucose levels in addition to the effects on levels of lipids and BMI in type 2 diabetic patients.Results:The GA group showed significant reduction in fasting plasma glucose (FPG andHbA1c(P<0.05 within the GA group. Moreover, GA supplementation improvedlipid profiles; decreasedLDL-Cholesterol by 5.95%, total Cholesterol by 8.28% and triglyceride by 10.95% from baseline levels. HDL-Cholesterol showedsignificant increase by 19.89% within GA group(P<0.05, BMI was decreased significantly by 2.06% (95% CI: −0.98; −0.16, P<0.05.Conclusions:Gum Arabic is a dietary supplement for improving nutrition of type 2 diabetic patients; it has demonstrateda good effect on improving their poor glycemic

  8. [The effect of trandolapril, in monotherapy and associated with verapamil, on arterial pressure, albuminuria, and metabolic control in hypertensive patients with type 2 diabetes and albuminuria].

    Science.gov (United States)

    Fernández González, R; García Robles, R; Rodríguez Pérez, J C; Gómez Pajuelo, C; Moreno Carretero, E

    2001-01-01

    The aim of this study was to analyse the effect of the ACE-1, Trandolapril, alone or with Verapamil on blood pressure, albuminuria and metabolic profile in type 2 diabetic patients with hypertension and albuminuria. It was an open multicenter, consecutive and prospective study conducted in 281 patients. There was a four-week wash-out period of antihypertensive drugs, after which we carried out a measurement over a 24-h period of the urinary excretion of albumina (UEA). Blood pressure was recorded after at least 5 minutes of rest in the sitting position at 1 to 3 minute intervals with a mercury sphygmomanometer in good condition. Average BP was obtained from three consecutive readings. Within treatment changes were analysed using descriptive statistics and t-tests on the change from baseline. Analysis of variance, chi-square and Mc Nemar tests were also used. If after 8 weeks of treatment with Trandolapril 2 mg o.q.d. the patients were non-responders (mean blood pressure reduction of 5 mmHg or less) or their blood pressure remained uncontrolled (blood pressure > or = 140/90 mmHg), Verapamil 180 mg o.q.d. was added. Two hundred and thirty patients completed the 12 weeks study. Population included 157 (55.9%) males with an average of 61.7 +/- 9.2 years. Baseline measurements were systolic 165.4 +/- 14.6 and diastolic 94.8 +/- 8.5 mmHg blood pressures, fasting glucose 162.7 +/- 43.9 mg/dL, glycosylated hemoglobin (HbAlc) 6.8 +/- 1.2%, and albuminuria 520.9 +/- 602 mg/day. UEA fell significantly (p < 0.001) after treatment to 177.9 +/- 24.3 mg/day (CI 95%, 129.9 to 225.8). The percent reduction reached 29.6%. Albuminuria was lower than 30 mg/day in 47 patients. Blood pressure was completely controlled in 125 (54%) patients. Glucemia fell significantly (p < 0.001) to 153.2 +/- 42.7 mg/dL, and the HbAlc to 6.5 +/- 1.3% (p = 0.012). In summary, in those diabetic type 2 patients with arterial hypertension and proteinuria, Trandolapril alone or associated with Verapamil

  9. Effect of Metabolic Syndrome on the Functional Outcome of Corticosteroid Injection for Lateral Epicondylitis: Retrospective Matched Case-Control Study.

    Science.gov (United States)

    Roh, Young Hak; Oh, Minjoon; Noh, Jung Ho; Gong, Hyun Sik; Baek, Goo Hyun

    2017-09-07

    Both obesity and diabetes mellitus are well-known risk factors for tendinopathies. We retrospectively compared the efficacy of single corticosteroid injections in treating lateral epicondylitis in patients with and without metabolic syndrome (MetS). Fifty-one patients with lateral epicondylitis and MetS were age- and sex-matched with 51 controls without MetS. Pain severity, Disability of the Arm, Shoulder, and Hand score, and grip strength were assessed at base line and at 6, 12 and 24 weeks post-injection. The pain scores in the MetS group were greater than those in the control group at 6 and 12 weeks. The disability scores and grip strength in the MetS group were significantly worse than those of the control group at 6 weeks. However, there were no significant differences at 24 weeks between the groups in terms of pain, disability scores and grip strengths. After 24 weeks, three patients (6%) in the control group and five patients (10%) in the MetS group had surgical decompression (p = 0.46). Patients with MetS are at risk for poor functional outcome after corticosteroid injection for lateral epicondylitis in the short term, but in the long term there was no difference in outcomes of steroid injection in patients with and without MetS.

  10. Trade in goods

    DEFF Research Database (Denmark)

    Sørensen, Karsten Engsig

    2006-01-01

    An analysis of the rules governing trade in goods under the GATT agreement and the Agreement on Safeguards......An analysis of the rules governing trade in goods under the GATT agreement and the Agreement on Safeguards...

  11. Functional roles of FgLaeA in controlling secondary metabolism, sexual development, and virulence in Fusarium graminearum.

    Directory of Open Access Journals (Sweden)

    Hee-Kyoung Kim

    Full Text Available Fusarium graminearum, the causal agent of Fusarium head blight in cereal crops, produces mycotoxins such as trichothecenes and zearalenone in infected plants. Here, we focused on the function of FgLaeA in F. graminearum, a homolog of Aspergillus nidulans LaeA encoding the global regulator for both secondary metabolism and sexual development. Prior to gene analysis, we constructed a novel luciferase reporter system consisting of a transgenic F. graminearum strain expressing a firefly luciferase gene under control of the promoter for either TRI6 or ZEB2 controlling the biosynthesis of these mycotoxins. Targeted deletion of FgLaeA led to a dramatic reduction of luminescence in reporter strains, indicating that FgLaeA controls the expression of these transcription factors in F. graminearum; reduced toxin accumulation was further confirmed by GC-MS analysis. Overexpression of FgLaeA caused the increased production of trichothecenes and additional metabolites. RNA seq-analysis revealed that gene member(s belonging to ~70% of total tentative gene clusters, which were previously proposed, were differentially expressed in the ΔFgLaeA strain. In addition, ΔFgLaeA strains exhibited an earlier induction of sexual fruiting body (perithecia formation and drastically reduced disease symptoms in wheat, indicating that FgLaeA seems to negatively control perithecial induction, but positively control virulence toward the host plant. FgLaeA was constitutively expressed under both mycotoxin production and sexual development conditions. Overexpression of a GFP-FgLaeA fusion construct in the ΔFgLaeA strain restored all phenotypic changes to wild-type levels and led to constitutive expression of GFP in both nuclei and cytoplasm at different developmental stages. A split luciferase assay demonstrated that FgLaeA was able to interact with FgVeA, a homolog of A. nidulans veA. Taken together, these results demonstrate that FgLaeA, a member of putative FgVeA complex

  12. The Efficacy of Acupuncture on Anthropometric Measures and the Biochemical Markers for Metabolic Syndrome: A Randomized Controlled Pilot Study

    Directory of Open Access Journals (Sweden)

    Mingjuan Han

    2017-01-01

    Full Text Available Background. Many previous studies have shown the potential therapeutic effect of acupuncture for metabolic syndrome (MetS. However, most of these studies were limited by short durations of observation and a lack of sham acupuncture as control. We designed a randomized controlled trial, used sham acupuncture as the control, and evaluated the efficacy over 12 weeks of treatment and 12 weeks of follow-up. Methods/Design. The study was designed as a multicentre, parallel-group, randomized, double-blinded trial. 40 patients were randomly assigned to two groups: treatment group (treated with acupuncture and control group (treated with sham acupuncture. Outcomes were measured at 4, 8, and 12 weeks and 3 months after treatment. Results. 33 participants (17 in acupuncture group and 16 in control group completed the treatment and the follow-up. Decreases from baseline in mean waist circumference (WC and weight at the end of treatment were 4.85 cm (95% CI [2.405,5.595] and 4.00 kg (95% CI [1.6208,4.4498] in acupuncture group and 1.62 cm and 1.64 kg in control group (P<0.01. The changes in mean glycosylated haemoglobin (HbA1c, triglycerides (TG, total cholesterol (TC, and blood pressure in acupuncture group were greater than the changes in control group (P<0.05, P<0.01. Conclusion. Acupuncture decreases WC, HC, HbA1c, TG, and TC values and blood pressure in MetS.

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

    NARCIS (Netherlands)

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

    2017-01-01

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

  14. Pharmacokinetics of diclofenac in healthy controls with wild-type phenotype for CYP2C9 shows metabolism variability

    Directory of Open Access Journals (Sweden)

    M. Martín-De Saro

    2017-04-01

    Conclusions: This data indicate that CYP2C9 is not the only enzyme responsible of the metabolism of diclofenac, so it is important to analyze other cytochromes and their variants potentially involved in the metabolism of this drug.

  15. Metabolic Heat Regenerated Temperature Swing Adsorption for CO2, Thermal and Humidity Control, Phase II

    Data.gov (United States)

    National Aeronautics and Space Administration — MTSA technology specifically addresses the thermal, CO2 and humidity control challenges faced by Portable Life Support Systems (PLSS) to be used in NASA's...

  16. Good Concrete Activity Is Good Mental Activity

    Science.gov (United States)

    McDonough, Andrea

    2016-01-01

    Early years mathematics classrooms can be colourful, exciting, and challenging places of learning. Andrea McDonough and fellow teachers have noticed that some students make good decisions about using materials to assist their problem solving, but this is not always the case. These experiences lead her to ask the following questions: (1) Are…

  17. A Good Suit Beats a Good Idea.

    Science.gov (United States)

    Machiavelli, Nick

    1992-01-01

    Inspired by Niccolo Machiavelli, this column offers beleaguered school executives advice on looking good, dressing well, losing weight, beating the proper enemy, and saying nothing. Administrators who follow these simple rules should have an easier life, jealous colleagues, well-tended gardens, and respectful board members. (MLH)

  18. Role of a critical visceral adipose tissue threshold (CVATT) in metabolic syndrome: implications for controlling dietary carbohydrates: a review

    OpenAIRE

    Freedland Eric S

    2004-01-01

    Abstract There are likely many scenarios and pathways that can lead to metabolic syndrome. This paper reviews mechanisms by which the accumulation of visceral adipose tissue (VAT) may contribute to the metabolic syndrome, and explores the paradigm of a critical VAT threshold (CVATT). Exceeding the CVATT may result in a number of metabolic disturbances such as insulin resistance to glucose uptake by cells. Metabolic profiles of patients with visceral obesity may substantially improve after onl...

  19. Effects of a high O2 dynamic-controlled atmosphere technology on the browning of postharvest white mushroom ( Agaricus bisporus) in relation to energy metabolism.

    Science.gov (United States)

    Li, Ling; Sun, Han; Kitazawa, Hiroaki; Wang, Xiangyou

    2017-07-01

    Browning is one of the main problems in senescence of mushrooms, and it is also one of the most important attributes accounting for the loss of the quality and reduction in market value. In order to study the relationship between the energy metabolism and the browning of white mushroom under high O 2 dynamic-controlled atmosphere (HO-DCA), mushrooms were stored in 100% O 2 (SCA1), 80% O 2  + 20% CO 2 (SCA2), 100% O 2 for three days and then transferred into the treatment of 80% O 2  + 20% CO 2 (HO-DCA) at 2 ± 1 ℃ and air as control. In this study, adenosine triphosphate (ATP) content, energy charge level, sensory evaluation, browning of surface and flesh, cell membrane integrity, exogenous ATP, polyphenol oxidase (PPO) and peroxidase (POD) activity and genes encoding PPO of the white mushroom were investigated. These were all closely related to the browning of products. The optimal storage condition of the HO-DCA treatment could delay the browning of pericarp and flesh tissues of the mushrooms, inhibit PPO activity and reduce the relative expression levels of the three genes encoding PPO. Meanwhile, it maintained moderate POD activity, good sensory properties and cell membrane integrity in a certain extent and thus slowed down the senescence of mushrooms. Results indicated that there was a positive correlation between the ATP content and whitening index ( r = 0.901). In addition, HO-DCA maintained a higher ATP level, prolonged the storage time to 28 days and it might be an ideal strategy for preserving the quality of mushroom during storage.

  20. Is the admission test for a course in medicine a good predictor of academic performance? A case-control experience at the school of medicine of Turin.

    Science.gov (United States)

    Migliaretti, Giuseppe; Bozzaro, Salvatore; Siliquini, Roberta; Stura, Ilaria; Costa, Giuseppe; Cavallo, Franco

    2017-12-01

    The usefulness of university admission tests to medical schools has been discussed in recent years. In the academic year 2014-15 in Italy, several students who failed the admission test appealed to the regional administrative court ('Tribunale Amministrativo Regionale'-TAR) requesting to be included, despite their test results, and all were admitted to their respective courses. The existence of this population of students generated a control group, in order to evaluate the predictive capacity of the admission test. The aim of the present work is to discuss the ability of university admission tests to predict subsequent academic success. The study involved 683 students who enrolled onto the first year of the degree course in medicine in the academic year 2014-15 at the University of Turin (Molinette and San Luigi Gonzaga colleges). The students were separated into two categories: those who passed the admission test (n1=531) and those who did not pass the admission test but won their appeal in the TAR (n2=152). The validity of the admission test was analysed using specificity, sensitivity, positive and negative likelihood ratios (LH+, LH-), receiver operating characteristic (ROC) curves, area under the ROC curve (AUC), and relative (95% CI). The results showed that the admission test appeared to be a good tool for predicting the academic performances in the first year of the course (AUC=0.70, 95% CI 0.64 to 0.76). Moreover, some subject areas seemed to have a greater discriminating capacity than others. In general, students who obtained a high score in scientific questions were more likely to obtain the required standards during the first year (LH+ 1.22, 95% CI 1.14 to 1.25). Based on a consistent statistical approach, our study seems to confirm the ability of the admission test to predict academic success in the first year at the school of medicine of Turin. © Article author(s) (or their employer(s) unless otherwise stated in the text of the article) 2017. All

  1. THE ROLE OF METABOLIC SURGERY FOR PATIENTS WITH OBESITY GRADE I AND TYPE 2 DIABETES NOT CONTROLLED CLINICALLY.

    Science.gov (United States)

    Campos, Josemberg; Ramos, Almino; Szego, Thomaz; Zilberstein, Bruno; Feitosa, Heládio; Cohen, Ricardo

    Even considering the advance of the medical treatment in the last 20 years with new and more effective drugs, the outcomes are still disappointing as the control of obesity and type 2 Diabetes Mellitus (T2DM) with a large number of patients under the medical treatment still not reaching the desired outcomes. To present a Metabolic Risk Score to better guide the surgical indication for T2DM patients with body mass index (BMI) where surgery for obesity is still controversial. Research was conducted in Pubmed, Medline, Pubmed Central, Scielo and Lilacs between 2003-2015 correlating headings: metabolic surgery, obesity and type 2 diabetes mellitus. In addition, representatives of the societies involved, as an expert panel, issued opinions. Forty-five related articles were analyzed by evidence-based medicine criteria. Grouped opinions sought to answer the following questions: Why metabolic and not bariatric surgery?; Mechanisms involved in glycemic control; BMI as a single criterion for surgical indication for uncontrolled T2DM; Results of metabolic surgery studies in BMIScielo e Lilacs entre 2003-2015 correlacionando os descritores:cirurgia metabólica, obesidade e diabete melito tipo 2. Adicionalmente, representantes das sociedades envolvidas emitiram opiniões em pontos nos quais não existia na literatura trabalhos com graus de evidência elevados. Foram encontrados 45 artigos relacionados que foram analisados pelos critérios da medicina baseada em evidências. As opiniões agrupadas procuraram responder as seguintes questões: Porque cirurgia metabólica e não bariátrica?; Mecanismos envolvidos no controle glicêmico; IMC como critério isolado de indicação cirúrgica para o DMT2 não controlado; Resultados de estudos de cirurgia metabólica em IMC<35 kg/m2; Segurança da cirurgia metabólica em pacientes com IMC<35 kg/m2; Efeitos em longo prazo da cirurgia em pacientes com IMC inicial <35 kg/m2; Proposta de Escore de Risco Metabólico. A cirurgia metab

  2. Demographic and personal factors associated with metabolic control and self-care in youth with type 1 diabetes

    DEFF Research Database (Denmark)

    Neylon, Orla M.; O'Connell, Michele A.; Skinner, Timothy C.

    2013-01-01

    Optimal use of recent technological advances in insulin delivery and glucose monitoring remain limited by the impact of behaviour on self-care. In recent years, there has been a resurgence of interest in psychosocial methods of optimizing care in youth with type 1 diabetes. We therefore sought...... studies fulfilled the inclusion criteria. These studies have indicated that identifiable individual characteristics in each domain are robustly associated with metabolic control and/or self-care in children and adolescents. We present these characteristics and propose a theoretical model...... of their interactions and effect on diabetes outcomes. There is currently no consensus regarding patient selection for insulin pump therapy. In this era of scarce healthcare resources, it may be prudent to identify youth requiring increased psychosocial support prior to regimen intensification. The importance...

  3. Metformin for weight loss and metabolic control in overweight outpatients with schizophrenia and schizoaffective disorder.

    Science.gov (United States)

    Jarskog, L Fredrik; Hamer, Robert M; Catellier, Diane J; Stewart, Dawn D; Lavange, Lisa; Ray, Neepa; Golden, Lauren H; Lieberman, Jeffrey A; Stroup, T Scott

    2013-09-01

    The purpose of this study was to determine whether metformin promotes weight loss in overweight outpatients with chronic schizophrenia or schizoaffective disorder. In a double-blind study, 148 clinically stable, overweight (body mass index [BMI] ≥27) outpatients with chronic schizophrenia or schizoaffective disorder were randomly assigned to receive 16 weeks of metformin or placebo. Metformin was titrated up to 1,000 mg twice daily, as tolerated. All patients continued to receive their prestudy medications, and all received weekly diet and exercise counseling. The primary outcome measure was change in body weight from baseline to week 16. Fifty-eight (77.3%) patients who received metformin and 58 (81.7%) who received placebo completed 16 weeks of treatment. Mean change in body weight was -3.0 kg (95% CI=-4.0 to -2.0) for the metformin group and -1.0 kg (95% CI=-2.0 to 0.0) for the placebo group, with a between-group difference of -2.0 kg (95% CI=-3.4 to -0.6). Metformin also demonstrated a significant between-group advantage for BMI (-0.7; 95% CI=-1.1 to -0.2), triglyceride level (-20.2 mg/dL; 95% CI=-39.2 to -1.3), and hemoglobin A1c level (-0.07%; 95% CI=-0.14 to -0.004). Metformin-associated side effects were mostly gastrointestinal and generally transient, and they rarely led to treatment discontinuation. Metformin was modestly effective in reducing weight and other risk factors for cardiovascular disease in clinically stable, overweight outpatients with chronic schizophrenia or schizoaffective disorder over 16 weeks. A significant time-by-treatment interaction suggests that benefits of metformin may continue to accrue with longer treatment. Metformin may have an important role in diminishing the adverse consequences of obesity and metabolic impairments in patients with schizophrenia.

  4. Genetic Polymorphisms in Vitamin D Metabolism and Signaling Genes and Risk of Breast Cancer: A Nested Case-Control Study.

    Directory of Open Access Journals (Sweden)

    Tess V Clendenen

    Full Text Available Genetic polymorphisms in vitamin D metabolism and signaling genes have been inconsistently associated with risk of breast cancer, though few studies have examined SNPs in vitamin D-related genes other than the vitamin D receptor (VDR gene and particularly have not examined the association with the retinoid X receptor alpha (RXRA gene which may be a key vitamin D pathway gene. We conducted a nested case-control study of 734 cases and 1435 individually matched controls from a population-based prospective cohort study, the Northern Sweden Mammary Screening Cohort. Tag and functional SNPs were genotyped for the VDR, cytochrome p450 24A1 (CYP24A1, and RXRA genes. We also genotyped specific SNPs in four other genes related to vitamin D metabolism and signaling (GC/VDBP, CYP2R1, DHCR7, and CYP27B1. SNPs in the CYP2R1, DHCR7, and VDBP gene regions that were associated with circulating 25(OHD concentration in GWAS were also associated with plasma 25(OHD in our study (p-trend <0.005. After taking into account the false discovery rate, these SNPs were not significantly associated with breast cancer risk, nor were any of the other SNPs or haplotypes in VDR, RXRA, and CYP24A1. We observed no statistically significant associations between polymorphisms or haplotypes in key vitamin D-related genes and risk of breast cancer. These results, combined with the observation in this cohort and most other prospective studies of no association of circulating 25(OHD with breast cancer risk, do not support an association between vitamin D and breast cancer risk.

  5. Differential effects of saturated fatty acids on the risk of metabolic syndrome: a matched case-control and meta-analysis study.

    Science.gov (United States)

    Yang, Wei-Sin; Chen, Pei-Chun; Hsu, Hsiu-Ching; Su, Ta-Chen; Lin, Hung-Ju; Chen, Ming-Fong; Lee, Yuan-Teh; Chien, Kuo-Liong

    2018-06-01

    We investigated the association between plasma saturated fatty acids (SFAs) and the risk of metabolic syndrome among ethnic Chinese adults in Taiwan who attended a health check-up center. A case-control study based on 1000 cases of metabolic syndrome and 1:1 matched control participants (mean age, 54.9 ± 10.7 y; 36% females) were recruited. Metabolic syndrome was defined according to the criteria of the International Diabetes Federation. Gas chromatography was used to measure the distribution of fatty acids in plasma (% of total fatty acids). Even-chain SFAs, including 14:0, 16:0, and 18:0, were associated with metabolic syndrome; the adjusted odds ratio [OR] and 95% confidence interval [CI] per standard deviation [SD] difference was 3.32, [1.98-5.59]; however, very-long-chain SFAs, including 20:0, 21:0, 22:0, 23:0, and 24:0, were inversely associated with metabolic syndrome. The adjusted OR [95% CI] per SD difference was 0.67 [0.58-0.78]. The area under the receiver operative characteristic curve increased from 0.814 in the basic model to 0.815 (p = 0.54, compared with the basic model), 0.818 (p metabolic syndrome, implying that SFAs are not homogenous for the effects. Copyright © 2018 Elsevier Inc. All rights reserved.

  6. The effect of a prenatal lifestyle intervention on glucose metabolism: results of the Norwegian Fit for Delivery randomized controlled trial.

    Science.gov (United States)

    Sagedal, Linda R; Vistad, Ingvild; Øverby, Nina C; Bere, Elling; Torstveit, Monica K; Lohne-Seiler, Hilde; Hillesund, Elisabet R; Pripp, Are; Henriksen, Tore

    2017-06-02

    The effectiveness of prenatal lifestyle intervention to prevent gestational diabetes and improve maternal glucose metabolism remains to be established. The Norwegian Fit for Delivery (NFFD) randomized, controlled trial studied the effect of a combined lifestyle intervention provided to a general population, and found significantly lower gestational weight gain among intervention participants but no improvement in obstetrical outcomes or the proportion of large infants. The aim of the present study is to examine the effect of the NFFD intervention on glucose metabolism, including an assessment of the subgroups of normal-weight and overweight/obese participants. Healthy, non-diabetic women expecting their first child, with pre-pregnancy body mass index (BMI) ≥19 kg/m 2 , age ≥ 18 years and a singleton pregnancy of ≤20 gestational-weeks were enrolled from healthcare clinics in southern Norway. Gestational weight gain was the primary endpoint. Participants (n = 606) were individually randomized to intervention (two dietary consultations and access to twice-weekly exercise groups) or control group (routine prenatal care). The effect of intervention on glucose metabolism was a secondary endpoint, measuring glucose (fasting and 2-h following 75-g glucose load), insulin, homeostatic assessment of insulin resistance (HOMA-IR) and leptin levels at gestational-week 30. Blood samples from 557 (91.9%) women were analyzed. For the total group, intervention resulted in reduced insulin (adj. Mean diff -0.91 mU/l, p = 0.045) and leptin levels (adj. Mean diff -207 pmol/l, p = 0.021) compared to routine care, while glucose levels were unchanged. However, the effect of intervention on both fasting and 2-h glucose was modified by pre-pregnancy BMI (interaction p = 0.030 and p = 0.039, respectively). For overweight/obese women (n = 158), intervention was associated with increased risk of at least one glucose measurement exceeding International Association of

  7. Meal replacement based on Human Ration modulates metabolic risk factors during body weight loss: a randomized controlled trial.

    Science.gov (United States)

    Alves, Natalia Elizabeth Galdino; Enes, Bárbara Nery; Martino, Hércia Stampini Duarte; Alfenas, Rita de Cássia Gonçalves; Ribeiro, Sônia Machado Rocha

    2014-04-01

    A meal replacement may be an effective strategy in the management of obesity to increase antioxidant intake, attenuating oxidative stress and inflammation. In the present study, we investigated the efficacy of a new nutritional supplement to reduce metabolic risk parameters in obese women. In a randomized controlled crossover study (2 × 2), 22 women (percentage body fat 40.52 ± 3.75%; body mass index-BMI 28.72 ± 2.87 kg/m²; 35.04 ± 5.6 years old) were allocated into two treatments: hypocaloric diet and drink containing "Human Ration" (HR) consumption (CRHR), and hypocaloric diet and control drink consumption (CR). The study consisted of 2 periods of 5 weeks with 1 week of washout in two orders (CR → CRHR and CRHR → CR). Caloric restriction was 15%, based on estimated energy requirement. Anthropometric, clinical and metabolic risk parameters were assessed at baseline and at the end of each period. Some metabolic risk factors were favorably modulated in both interventions: reduction in body weight (CR -0.74 ± 1.27 kg; p = 0.01; CRHR -0.77 ± 1.3 kg; p = 0.02), body mass index (BMI) (CR -0.27 ± 0.51 kg/m²; p = 0.02; CRHR -0.30 ± 0.52 kg/m²; p = 0.01) and HOMA-IR (CR -0.35 ± 0.82; p = 0.02, CRHR -0.41 ± 0.83; p = 0.03). However, CRHR reduced waist circumference (-2.54 ± 2.74 cm; p < 0.01) and gynoid fat (-0.264 ± 0.28 g; p < 0.01), and increased HDL-c levels (0.08 ± 0.15 mmol/l; p = 0.04). Associated with hypocaloric diet, the intake of a nutritional supplement rich in phytochemicals as a breakfast substitute for 5 weeks had no additional effect on weight reduction than caloric restriction alone, but increased central lipolysis and improved the lipoprotein profile.

  8. SIRT1 genetic variants associate with the metabolic response of Caucasians to a controlled lifestyle intervention – the TULIP Study

    Directory of Open Access Journals (Sweden)

    Stefan Norbert

    2008-11-01

    Full Text Available Abstract Background Sirtuin1 (SIRT1 regulates gene expression in distinct metabolic pathways and mediates beneficial effects of caloric restriction in animal models. In humans, SIRT1 genetic variants associate with fasting energy expenditure. To investigate the relevance of SIRT1 for human metabolism and caloric restriction, we analyzed SIRT1 genetic variants in respect to the outcome of a controlled lifestyle intervention in Caucasians at risk for type 2 diabetes. Methods A total of 1013 non-diabetic Caucasians from the Tuebingen Family Study (TUEF were genotyped for four tagging SIRT1 SNPs (rs730821, rs12413112, rs7069102, rs2273773 for cross-sectional association analyses with prediabetic traits. SNPs that associated with basal energy expenditure in the TUEF cohort were additionally analyzed in 196 individuals who underwent a controlled lifestyle intervention (Tuebingen Lifestyle Intervention Program; TULIP. Multivariate regressions analyses with adjustment for relevant covariates were performed to detect associations of SIRT1 variants with the changes in anthropometrics, weight, body fat or metabolic characteristics (blood glucose, insulin sensitivity, insulin secretion and liver fat, measured by magnetic resonance techniques after the 9-month follow-up test in the TULIP study. Results Minor allele (X/A carriers of rs12413112 (G/A had a significantly lower basal energy expenditure (p = 0.04 and an increased respiratory quotient (p = 0.02. This group (rs12413112: X/A was resistant against lifestyle-induced improvement of fasting plasma glucose (GG: -2.01%, X/A: 0.53%; p = 0.04, had less increase in insulin sensitivity (GG: 17.3%, X/A: 9.6%; p = 0.05 and an attenuated decline in liver fat (GG: -38.4%, X/A: -7.5%; p = 0.01. Conclusion SIRT1 plays a role for the individual lifestyle intervention response, possibly owing to decreased basal energy expenditure and a lower lipid-oxidation rate in rs12413112 X/A allele carriers. SIRT1 genetic

  9. Metabolic control by sirtuins and other enzymes that sense NAD(+), NADH, or their ratio

    DEFF Research Database (Denmark)

    Anderson, Kristin A; Madsen, Andreas S; Olsen, Christian A

    2017-01-01

    NAD(+) is a dinucleotide cofactor with the potential to accept electrons in a variety of cellular reduction-oxidation (redox) reactions. In its reduced form, NADH is a ubiquitous cellular electron donor. NAD(+), NADH, and the NAD(+)/NADH ratio have long been known to control the activity of several...... oxidoreductase enzymes. More recently, enzymes outside those participating directly in redox control have been identified that sense these dinucleotides, including the sirtuin family of NAD(+)-dependent protein deacylases. In this review, we highlight examples of non-redox enzymes that are controlled by NAD......(+), NADH, or NAD(+)/NADH. In particular, we focus on the sirtuin family and assess the current evidence that the sirtuin enzymes sense these dinucleotides and discuss the biological conditions under which this might occur; we conclude that sirtuins sense NAD(+), but neither NADH nor the ratio. Finally, we...

  10. Periodontal health, salivary status, and metabolic control in children with type 1 diabetes mellitus.

    Science.gov (United States)

    Aren, Gamze; Sepet, Elif; Ozdemir, Didem; Dinççağ, Nevin; Güvener, Bora; Firatli, Erhan

    2003-12-01

    The aim of this study was to determine whether detectable periodontal destruction and alterations in the salivary status were present with duration of diabetes in children with type 1 insulin-dependent diabetes mellitus (type 1 DM) as compared to healthy controls. Sixteen newly diagnosed children with DM (group 1), 16 children with type 1 DM of long duration (group 2), and 16 healthy children (group 3) participated in the study. Periodontal health was assessed by plaque index, gingival index, bleeding on probing, and periodontal probing depths. The flow rate, pH, buffering capacity, and peroxidase activities of stimulated saliva were determined. The data were analyzed by Kruskall-Wallis, Student t test, and Pearson's correlation analysis. The mean values for fasting blood glucose levels for the diabetic groups were significantly higher than for the controls. The mean values for salivary buffering capacities and salivary pH from the diabetic groups were significantly lower than for the controls. The plaque index values for the diabetic groups were significantly higher than for the controls. The mean gingival index value for group 1 was significantly lower than for group 2. The mean periodontal probing depths for group 1 were similar to those of the non-DM controls, but the mean periodontal probing depths for group 2 were significantly greater than for both the non-DM controls and group 1. Group 1 had significantly greater bleeding on probing scores than did the other groups (P diabetic subjects affects the periodontal probing depths, salivary pH, buffering capacity, and peroxidase activity.

  11. Mathematical modelling of metabolism

    DEFF Research Database (Denmark)

    Gombert, Andreas Karoly; Nielsen, Jens

    2000-01-01

    Mathematical models of the cellular metabolism have a special interest within biotechnology. Many different kinds of commercially important products are derived from the cell factory, and metabolic engineering can be applied to improve existing production processes, as well as to make new processes...... availability of genomic information and powerful analytical techniques, mathematical models also serve as a tool for understanding the cellular metabolism and physiology....... available. Both stoichiometric and kinetic models have been used to investigate the metabolism, which has resulted in defining the optimal fermentation conditions, as well as in directing the genetic changes to be introduced in order to obtain a good producer strain or cell line. With the increasing...

  12. Antipsychotic drugs may worsen metabolic control in type 2 diabetes mellitus

    NARCIS (Netherlands)

    Spoelstra, JA; Stolk, RP; Cohen, D; Klungel, OH; Erkens, JA; Leufkens, HGM; Grobbee, DE

    (B)ackground: Several studies have indicated that type 2 diabetes mellitus is more common among schizophrenic patients than in the general population. In this study, we investigated whether the use of antipsychotic drugs in patients with diabetes leads to worsening of glycemic control. Method: In

  13. Roles of Protein Arginine Methyltransferases in the Control of Glucose Metabolism

    Directory of Open Access Journals (Sweden)

    Hye-Sook Han

    2014-12-01

    Full Text Available Glucose homeostasis is tightly controlled by the regulation of glucose production in the liver and glucose uptake into peripheral tissues, such as skeletal muscle and adipose tissue. Under prolonged fasting, hepatic gluconeogenesis is mainly responsible for glucose production in the liver, which is essential for tissues, organs, and cells, such as skeletal muscle, the brain, and red blood cells. Hepatic gluconeogenesis is controlled in part by the concerted actions of transcriptional regulators. Fasting signals are relayed by various intracellular enzymes, such as kinases, phosphatases, acetyltransferases, and deacetylases, which affect the transcriptional activity of transcription factors and transcriptional coactivators for gluconeogenic genes. Protein arginine methyltransferases (PRMTs were recently added to the list of enzymes that are critical for regulating transcription in hepatic gluconeogenesis. In this review, we briefly discuss general aspects of PRMTs in the control of transcription. More specifically, we summarize the roles of four PRMTs: PRMT1, PRMT 4, PRMT 5, and PRMT 6, in the control of hepatic gluconeogenesis through specific regulation of FoxO1- and CREB-dependent transcriptional events.

  14. The Global Regulator Spx Functions in the Control of Organosulfur Metabolism in Bacillus subtilis†

    Science.gov (United States)

    Choi, Soon-Yong; Reyes, Dindo; Leelakriangsak, Montira; Zuber, Peter

    2006-01-01

    Spx is a global transcriptional regulator of the oxidative stress response in Bacillus subtilis. Its target is RNA polymerase, where it contacts the α subunit C-terminal domain. Recently, evidence was presented that Spx participates in sulfate-dependent control of organosulfur utilization operons, including the ytmI, yxeI, ssu, and yrrT operons. The yrrT operon includes the genes that function in cysteine synthesis from S-adenosylmethionine through intermediates S-adenosylhomocysteine, ribosylhomocysteine, homocysteine, and cystathionine. These operons are also negatively controlled by CymR, the repressor of cysteine biosynthesis operons. All of the operons are repressed in media containing cysteine or sulfate but are derepressed in medium containing the alternative sulfur source, methionine. Spx was found to negatively control the expression of these operons in sulfate medium, in part, by stimulating the expression of the cymR gene. In addition, microarray analysis, monitoring of yrrT-lacZ fusion expression, and in vitro transcription studies indicate that Spx directly activates yrrT operon expression during growth in medium containing methionine as sole sulfur source. These experiments have uncovered additional roles for Spx in the control of gene expression during unperturbed, steady-state growth. PMID:16885442

  15. Improved metabolic control and hepatic oxidative biomarkers with the periconception use of Helichrysum plicatum ssp. plicatum.

    Science.gov (United States)

    Sezik, M; Aslan, M; Orhan, D D; Erdemoglu, E; Pekcan, M; Mungan, T; Sezik, E

    2010-02-01

    Our aim was to investigate the hypoglycaemic and antioxidant effects of the Helichrysum plicatum ssp. plicatum (HPsP) plant extract in the streptozotocin-induced type 1 diabetes rat model during pregnancy. Five groups (n = 8, each) were formed: (1) diabetic non-mated control, (2) non-diabetic mated control, (3) diabetic mated control, (4) diabetic non-mated treatment and (5) diabetic mated treatment. The HPsP extract was administered orally for 15 days (250 mg/kg body weight), beginning 3 days before mating. The extract led to decreased blood glucose, increased serum insulin, and decreased serum triglycerides in pregnant and non-pregnant diabetic animals. Liver thiobarbituric acid reactive substances (TBARS) and reduced glutathione (GSH) measurements in extract-treated diabetics were similar to non-diabetic pregnant controls, indicating probable reversal of increased lipid peroxidation in the liver. The mean pup number tended to increase (p = 0.06) with extract administration. In conclusion, the beneficial effects we encountered with the periconception use of the studied herbal extract warrant further investigation.

  16. Autonomic control of heart rate by metabolically sensitive skeletal muscle afferents in humans

    DEFF Research Database (Denmark)

    Fisher, James P; Seifert, Thomas; Hartwich, Doreen

    2010-01-01

    moderate (PEI-M) and high (PEI-H) intensity isometric handgrip performed at 25% and 40% maximum voluntary contraction, under control (no drug), parasympathetic blockade (glycopyrrolate) and beta-adrenergic blockade (metoprolol or propranalol) conditions, while beat-to-beat HR and BP were continuously...

  17. Changes in Angiotensin Receptor Distribution and in Aortic Morphology Are Associated with Blood Pressure Control in Aged Metabolic Syndrome Rats

    Directory of Open Access Journals (Sweden)

    Verónica Guarner-Lans

    2016-01-01

    Full Text Available The role of the renin-angiotensin system (RAS in blood pressure regulation in MS during aging is unknown. It participates in metabolic syndrome (MS and aging regulating vascular tone and remodeling. RAS might participate in a compensatory mechanism decreasing blood pressure and allowing MS rats to reach 18 months of age and it might form part of therapeutical procedures to ameliorate MS. We studied histological changes and distribution of RAS receptors in aortas of MS aged rats. Electron microscopy images showed premature aging in MS since the increased fibrosis, enlarged endothelium, and invasion of this layer by muscle cells that was present in control 18-month-old aortas were also found in 6-month-old aortas from MS rats. AT1, AT2, and Mas receptors mediate the effects of Ang II and Ang 1-7, respectively. Fluorescence from AT2 decreased with age in control and MS aortas, while fluorescence of AT1 increased in aortas from MS rats at 6 months and diminished during aging. Mas expression increased in MS rats and remained unchanged in control rats. In conclusion, there is premature aging in the aortas from MS rats and the elevated expression of Mas receptor might contribute to decrease blood pressure during aging in MS.

  18. Prevalence and control of high blood pressure in primary care: results from the German Metabolic and Cardiovascular Risk Study (GEMCAS).

    Science.gov (United States)

    Balijepalli, Chakrapani; Bramlage, Peter; Lösch, Christian; Zemmrich, Claudia; Humphries, Karin H; Moebus, Susanne

    2014-06-01

    Contemporary epidemiological data on blood pressure readings, hypertension prevalence and control in unselected patient populations covering a broad age range are scarce. The aim here is to report the prevalence of high blood pressure and to identify factors associated with blood pressure control in a large German primary care sample. We used data from the German Metabolic and Cardiovascular Risk Study including 35 869 patients aged 18-99 years. High blood pressure was defined as systolic blood pressure ≥140 mm Hg and/or diastolic blood pressure ≥90 mm Hg or using antihypertensive therapy. Factors associated with blood pressure control among patients receiving antihypertensive therapy were examined using multiple logistic regressions to estimate odds ratios and 95% confidence intervals. The prevalence of high blood pressure, uncontrolled high blood pressure and untreated high blood pressure was 54.8%, 21.3% and 17.6%, respectively. Age >50 years (1.52; 1.40-1.65), male sex (1.30; 1.20-1.41), elevated waist circumference (1.55; 1.45-1.65), high cholesterol (1.24; 1.16-1.33), high triglycerides (1.11; 1.04-1.19) and concomitant diabetes (1.29; 1.20-1.40) were independently associated with uncontrolled high blood pressure. In a majority of patients we observed hypertension despite treatment for high blood pressures. Studies examining the reasons for treatment failure are highly warranted.

  19. Metformin for Weight Loss and Metabolic Control in Overweight Outpatients With Schizophrenia and Schizoaffective Disorder

    Science.gov (United States)

    Jarskog, L. Fredrik; Hamer, Robert M.; Catellier, Diane J.; Stewart, Dawn D.; LaVange, Lisa; Ray, Neepa; Golden, Lauren H.; Lieberman, Jeffrey A.; Stroup, T. Scott

    2013-01-01

    Objective The purpose of this study was to determine whether metformin promotes weight loss in overweight out-patients with chronic schizophrenia or schizoaffective disorder. Method In a double-blind study, 148 clinically stable, overweight (body mass index [BMI] ≥27) outpatients with chronic schizophrenia or schizoaffective disorder were randomly assigned to receive 16 weeks of metformin or placebo. Metformin was titrated up to 1,000 mg twice daily, as tolerated. All patients continued to receive their prestudy medications, and all received weekly diet and exercise counseling. The primary outcome measure was change in body weight from baseline to week 16. Results Fifty-eight (77.3%) patients who received metformin and 58 (81.7%) who received placebo completed 16 weeks of treatment. Mean change in body weight was −3.0 kg (95% CI=−4.0 to −2.0) for the metformin group and −1.0 kg (95% CI= −2.0 to 0.0) for the placebo group, with a between-group difference of −2.0 kg (95% CI=−3.4 to −0.6). Metformin also demonstrated a significant between-group advantage for BMI (−0.7; 95% CI=−1.1 to −0.2), triglyceride level (−20.2 mg/dL; 95% CI=−39.2 to −1.3), and hemoglobin A1c level (−0.07%; 95% CI=−0.14 to −0.004). Metformin-associated side effects were mostly gastrointestinal and generally transient, and they rarely led to treatment discontinuation. Conclusions Metformin was modestly effective in reducing weight and other risk factors for cardiovascular disease in clinically stable, overweight outpatients with chronic schizophrenia or schizoaffective disorder over 16 weeks. A significant time-by-treatment interaction suggests that benefits of metformin may continue to accrue with longer treatment. Metformin may have an important role in diminishing the adverse consequences of obesity and metabolic impairments in patients with schizophrenia. PMID:23846733

  20. A structured approach to the study of metabolic control principles in intact and impaired mitochondria

    OpenAIRE

    Huber, Heinrich J.; Connolly, Niamh M. C.; Dussmann, Heiko; Prehn, Jochen H. M.

    2012-01-01

    We devised an approach to extract control principles of cellular bioenergetics for intact and impaired mitochondria from ODE-based models and applied it to a recently established bioenergetic model of cancer cells. The approach used two methods for varying ODE model parameters to determine those model components that, either alone or in combination with other components, most decisively regulated bioenergetic state variables. We found that, while polarisation of the mitochondrial membrane pot...

  1. Metabolic control by sirtuins and other enzymes that sense NAD+, NADH, or their ratio.

    Science.gov (United States)

    Anderson, Kristin A; Madsen, Andreas S; Olsen, Christian A; Hirschey, Matthew D

    2017-12-01

    NAD + is a dinucleotide cofactor with the potential to accept electrons in a variety of cellular reduction-oxidation (redox) reactions. In its reduced form, NADH is a ubiquitous cellular electron donor. NAD + , NADH, and the NAD + /NADH ratio have long been known to control the activity of several oxidoreductase enzymes. More recently, enzymes outside those participating directly in redox control have been identified that sense these dinucleotides, including the sirtuin family of NAD + -dependent protein deacylases. In this review, we highlight examples of non-redox enzymes that are controlled by NAD + , NADH, or NAD + /NADH. In particular, we focus on the sirtuin family and assess the current evidence that the sirtuin enzymes sense these dinucleotides and discuss the biological conditions under which this might occur; we conclude that sirtuins sense NAD + , but neither NADH nor the ratio. Finally, we identify future studies that might be informative to further interrogate physiological and pathophysiological changes in NAD + and NADH, as well as enzymes like sirtuins that sense and respond to redox changes in the cell. Copyright © 2017 Elsevier B.V. All rights reserved.

  2. A human model of inflammatory cardio-metabolic dysfunction; a double blind placebo-controlled crossover trial

    Directory of Open Access Journals (Sweden)

    Mehta Nehal N

    2012-06-01

    Full Text Available Abstract Background Chronic inflammation may contribute to insulin resistance (IR, metabolic syndrome and atherosclerosis although evidence of causality is lacking in humans. We hypothesized that very low-dose experimental endotoxemia would induce adipose tissue inflammation and systemic IR during a low-grade but asymptomatic inflammatory response and thus provide an experimental model for future tests of pharmacologic and genomic modulation of cardio-metabolic traits in humans. Methods Ten healthy, human volunteers (50% male, 90% Caucasian, mean age 22.7 ± 3.8 were randomized in a double-masked, placebo-controlled, crossover study to separate 36-hour inpatient visits (placebo versus intravenous-LPS 0.6 ng/kg. We measured clinical symptoms via the McGill pain questionnaire and serial vital signs. Plasma and serum were collected for measurement of cytokines, C-reactive protein, insulin and glucose, serial whole blood & subcutaneous adipose tissue mRNA expression were measured by real-time PCR. HOMA-IR, a well-validated measure of IR was calculated to estimate insulin resistance, and frequently sampled intravenous glucose tolerance testing (FSIGTT was performed to confirm an insulin resistant state. We performed ANOVA and within subject ANOVA to understand the differences in cytokines, adipose tissue inflammation and IR before and after LPS or placebo. Results There was no significant difference between placebo and LPS in clinical responses of symptom scores, body temperature or heart rate. However, low-dose endotoxemia induced a rapid and transient 25-fold induction of plasma TNF-alpha and 100-fold increase in plasma IL-6 (Figure 1B (p p p = 0.01 increased with MCP-1 (peak 10-fold, F = 5.6, p p p p  Conclusions We present a low dose human endotoxemia model of inflammation which induces adipose tissue inflammation and systemic insulin resistance in the absence of overt clinical response. Such a model has the potential

  3. The common good

    OpenAIRE

    Argandoña, Antonio

    2011-01-01

    The concept of the common good occupied a relevant place in classical social, political and economic philosophy. After losing ground in the Modern age, it has recently reappeared, although with different and sometimes confusing meanings. This paper is the draft of a chapter of a Handbook; it explains the meaning of common good in the Aristotelian-Thomistic philosophy and in the Social Doctrine of the Catholic Church; why the common good is relevant; and how it is different from the other uses...

  4. Control analysis of the role of triosephosphate isomerase in glucose metabolism in Lactococcus lactis

    DEFF Research Database (Denmark)

    Solem, Christian; Købmann, Brian Jensen; Jensen, Peter Ruhdal

    2008-01-01

    Triosephosphate isomerase (TPI), which catalyses the conversion of dihydroxyacetone phosphate (DHAP) to glyceraldehyde-3-phosphate (G3P), was studied for its control on glycolysis and mixed acid production in L. lactis subspecies lactis IL1403 and L. lactis subspecies cremoris MG1363. Strains...... metabolites glucose-6-phosphate, fructose-1,6-bisphosphate and DHAP in the IL1403 derivatives were essentially unchanged for TPI activities from 26% to 225%. At a TPI activity of 3%, the level of DHAP increased four times. The finding that an increased level of DHAP coincides with an increase in formate...

  5. Transport of hazardous goods

    International Nuclear Information System (INIS)

    1989-01-01

    The course 'Transport of hazardous goods' was held in Berlin in November 1988 in cooperation with the Bundesanstalt fuer Materialforschung und -pruefung. From all lecturs, two are recorded separately: 'Safety of tank trucks - requirements on the tank, development possibiities of active and passive safety' and 'Requirements on the transport of radioactive materials - possible derivations for other hazardous goods'. The other lectures deal with hazardous goods law, requirements on packinging, risk assessment, railroad transport, hazardous goods road network, insurance matters, EC regulations, and waste tourism. (HSCH) [de

  6. On good ETOL forms

    DEFF Research Database (Denmark)

    Skyum, Sven

    1978-01-01

    This paper continues the study of ETOL forms and good EOL forms done by Maurer, Salomaa and Wood. It is proven that binary very complete ETOL forms exist, good synchronized ETOL forms exist and that no propagating or synchronized ETOL form can be very complete.......This paper continues the study of ETOL forms and good EOL forms done by Maurer, Salomaa and Wood. It is proven that binary very complete ETOL forms exist, good synchronized ETOL forms exist and that no propagating or synchronized ETOL form can be very complete....

  7. On Having a Good

    OpenAIRE

    Korsgaard, Christine M.

    2014-01-01

    In some recent papers I have been arguing that the concept ‘good-for’ is prior to the concept of ‘good’ (in the sense in which final ends are good), and exploring the implications of that claim. One of those implications is that everything that is good is good for someone. That implication seems to fall afoul of our intuitions about certain cases, such as the intuition that a world full of happy people and animals is better than a world full of miserable ones, even if the people and animals a...

  8. Randomised controlled trial of effect of whole soy replacement diet on features of metabolic syndrome in postmenopausal women: study protocol.

    Science.gov (United States)

    Liu, Zhao-Min; Ho, Suzanne; Hao, Yuan-Tao; Chen, Yu-Ming; Woo, Jean; Wong, Samuel Yeung-Shan; He, Qiqiang; Xie, Yao Jie; Tse, Lap Ah; Chen, Bailing; Su, Xue-Fen; Lao, Xiang-Qian; Wong, Carmen; Chan, Ruth; Ling, Wen-Hua

    2016-09-27

    Metabolic syndrome (MetS) is a public health problem in postmenopausal women. Whole soy foods are rich in unsaturated fats, high quality plant protein and various bioactive phytochemicals that may have a beneficial role in the management of MetS. The aim of the study is to examine the effect of whole soy replacement diet on the features of MetS among postmenopausal women. This will be a 12-month, randomised, single-blind, parallel controlled trial among 208 postmenopausal women at risk of MetS or with early MetS. After 4 weeks' run-in, subjects will be randomly allocated to one of two intervention groups, whole soy replacement group or control group, each for 12 months. Subjects in the whole soy group will be required to include four servings of whole soy foods (containing 25 g soy protein) into their daily diet iso-calorically, replacing red or processed meat and high fat dairy products. Subjects in the control group will remain on a usual diet. The outcome measures will include metabolic parameters as well as a 10-year risk for ischaemic cardiovascular disease. We hypothesise that the whole soy substitution diet will notably improve features of MetS in postmenopausal women at risk of MetS or with early MetS. The study will have both theoretical and practical significance. If proven effective, the application of the whole soy replacement diet model will be a safe, practical and economical strategy for MetS prevention and treatment. Ethics approval has been obtained from the Ethics Committee of the Chinese University of Hong Kong. The results will be disseminated via conference presentations and papers in academic peer reviewed journals. Data files will be deposited in an accessible repository. NCT02610322. Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://www.bmj.com/company/products-services/rights-and-licensing/

  9. Dental, periodontal and salivary conditions in diabetic children associated with metabolic control variables and nutritional plan adherence.

    Science.gov (United States)

    Díaz Rosas, C Y; Cárdenas Vargas, E; Castañeda-Delgado, J E; Aguilera-Galaviz, L A; Aceves Medina, M C

    2018-06-01

    Diabetes mellitus is a chronic disease that has manifestations other than alterations in endocrine regulation or in metabolic pathways. Several diseases of the oral cavity have been associated with diabetes mellitus type 1 and 2 in young people according to their evolution. Scarce information exists regarding the role of diabetes and its association with the oral health status in paediatric diabetic patients. The aims of the study were to assess the quality of saliva, saliva acidogenicity, dental caries experience, fluorosis and periodontal status in diabetic patients and to evaluate their relationship with metabolic control variables and nutritional plan adherence. The study population consisted of 60 paediatric patients with both types of diabetes mellitus. Saliva testing included stimulated flow, pH (using pH indicator strips), buffer capacity and Snyder's Test. DMFT/dmft and dental caries experience were determined on the basis of ICDAS II codes. The periodontal status was assessed by PI and GI and fluorosis by FI. Nutritional plan adherence was established from the subscale "Dietary Control" of the Diabetes Self-Management Profile questionnaire. Medical Data was retrieved from the clinical registers in the Diabetic Clinic. We describe the main characteristics of the oral cavity related variables of our population that might guide the clinical practice in similar settings; we found a dmft/DMFT of 1.71 ± 1.74 and 0.64 ± 1.03, PI of 1.91 ± 0.75, GI of 0.50 ± 0.56 and a fluorosis prevalence of 61%. We identified several correlated variables, which indicate strong associations between the nutritional habits of the patients and co-occurrence of oral cavity physiopathological alterations. Several correlations were found between acidogenic activity of the saliva (Snyder Test) and the percentage of adherence to the nutritional plan and to the dmft index. Furthermore, a significant correlation between the buffering capacity of the saliva and the glycemic control of

  10. Relationship between metabolic control and self-monitoring of blood glucose in insulin-treated patients with diabetes mellitus.

    Science.gov (United States)

    Soto González, Alfonso; Quintela Fernández, Niurka; Pumar López, Alfonso; Darias Garzón, Ricardo; Rivas Fernández, Margarita; Barberá Comes, Gloria

    2015-05-01

    To assess the relationship between metabolic control (MC) and frequency of self-monitoring of blood glucose (SMBG) in insulin-treated patients with type 1 (T1DM) and type 2 (T2DM) diabetes mellitus, and to analyze the factors associated to MC. A multicenter, cross-sectional, observational study was conducted in which endocrinologists enrolled diabetic patients treated with insulin who used a glucometer. The cut-off value for MC was HbA1c ≤ 7%. Grade of acceptance of the glucometer was assessed using a visual analogue scale (VAS). A total of 341 patients (53.5% males) with a mean age (SD) 52.8 (16.3) years, mean HbA1c of 7.69% (1.25) and 128 (37.5%) with T1DM and 211 (61.9%) with T2DM were evaluable. SMBG was done by 86.1% at least once weekly. No relationship was seen between MC and SMBG (P=.678) in the overall sample or in the T1DM (P=.940) or T2DM (P=.343) subgroups. In the logistic regression model, hyperglycemic episodes (Exp-b [risk] 1.794, P=0.022), falsely elevated HbA1c values (Exp-b 3.182, P=.005), and VAS (Exp-b 1.269, P=.008) were associated to poor MC in the total sample. Hyperglycemic episodes (Exp-b 2.538, P=.004), falsely elevated HbA1c values (Exp-b 3.125, P=.012), and VAS (Exp-b 1.316, P=.026) were associated to poor MC in the T2DM subgroup, while body mass index (Exp-b 1.143, P=.046) was associated to poor MC in the T1DM subgroup. In this retrospective, non-controlled study on patients with DM treated with insulin who used a glucometer, no relationship was seen between the degree of metabolic control and frequency of use of the glucometer. Copyright © 2014 SEEN. Published by Elsevier España, S.L.U. All rights reserved.

  11. [Quality control an assessment system. Its location within a program for food, nutrition and metabolic intervention].

    Science.gov (United States)

    Santana Porbén, S

    2012-01-01

    A design proposal for a HQCAS Hospital Quality Control and Assessment System of the nutritional and feeding care processes conducted in a hospital environment is presented in this article. The design proposal is accompanied of the results of inspections conducted by the hospital NST Nutritional Support Group between 2005-2010. The system design includes quality policies that should rule the useful and safe conduction of such processes, the recording and documentary foundations of the System, and the quality control and assessment exercises for the continuous verification of such established policies. The current state of the conduction of these processes was documented from secondary records opened by the NST after satisfying consultation requests from the medical care teams of the institution. Inspections conducted by the NST revealed that less than half of clinical charts contained information minimally enough for elaborating nutritional judgments, almost one-fifth of the assisted patients were on Nils Per Oris, for whom no nutritional support schemes were prescribed, and a low prescription and usage of artificial nutrition schemes. Corrective measures adopted by the NST served to significantly increase the rates of successful completion of inspected processes. Quality assurance of feeding and nutritional care processes is a practical as well as an intellectual activity subjected to constant remodeling, in order to always warrant the fulfillment of quality policies advanced by the NST, and thus, that the patient benefits from the prescribed nutritional intervention strategy.

  12. Continuous glucose profiles in obese and normal-weight pregnant women on a controlled diet: metabolic determinants of fetal growth.

    Science.gov (United States)

    Harmon, Kristin A; Gerard, Lori; Jensen, Dalan R; Kealey, Elizabeth H; Hernandez, Teri L; Reece, Melanie S; Barbour, Linda A; Bessesen, Daniel H

    2011-10-01

    We sought to define 24-h glycemia in normal-weight and obese pregnant women using continuous glucose monitoring (CGM) while they consumed a habitual and controlled diet both early and late in pregnancy. Glycemia was prospectively measured in early (15.7 ± 2.0 weeks' gestation) and late (27.7 ± 1.7 weeks' gestation) pregnancy in normal-weight (n = 22) and obese (n = 16) pregnant women on an ad libitum and controlled diet. Fasting glucose, triglycerides (early pregnancy only), nonesterified fatty acids (FFAs), and insulin also were measured. The 24-h glucose area under the curve was higher in obese women than in normal-weight women both early and late in pregnancy despite controlled diets. Nearly all fasting and postprandial glycemic parameters were higher in the obese women later in pregnancy, as were fasting insulin, triglycerides, and FFAs. Infants born to obese mothers had greater adiposity. Maternal BMI (r = 0.54, P = 0.01), late average daytime glucose (r = 0.48, P fasting insulin (r = 0.49, P fasting triglycerides (r = 0.67, P fasting FFAs (r = 0.54, P obese women without diabetes have higher daytime and nocturnal glucose profiles than normal-weight women despite a controlled diet both early and late in gestation. Body fat in infants, not birth weight, was related to maternal BMI, glucose, insulin, and FFAs, but triglycerides were the strongest predictor. These metabolic findings may explain higher rates of infant macrosomia in obese women, which might be targeted in trials to prevent excess fetal growth.

  13. Does an Algorithmic Approach to Using Brachytherapy and External Beam Radiation Result in Good Function, Local Control Rates, and Low Morbidity in Patients With Extremity Soft Tissue Sarcoma?

    Science.gov (United States)

    Klein, Jason; Ghasem, Alex; Huntley, Samuel; Donaldson, Nathan; Keisch, Martin; Conway, Sheila

    2018-03-01

    -grade soft tissue sarcomas can yield acceptable complication rates, good morbidity outcome scores, and a high degree of local control. Based on these results, we believe HDR-BT is best for patients with an anticipated close margin, a positive surgical margin, and for patients who are unlikely to receive a complex soft tissue procedure. Conversely, if a secondary procedure and/or soft tissue coverage are likely to be used, EBRT alone may be reasonable. Finally, combination therapy might be considered when the treatment volume exceeded the treatment field capacity for HDR-BT or when the catheters were used to boost a close or positive surgical margin. Level IV, therapeutic study.

  14. Integrative analysis of transgenic alfalfa (Medicago sativa L. suggests new metabolic control mechanisms for monolignol biosynthesis.

    Directory of Open Access Journals (Sweden)

    Yun Lee

    2011-05-01

    Full Text Available The entanglement of lignin polymers with cellulose and hemicellulose in plant cell walls is a major biological barrier to the economically viable production of biofuels from woody biomass. Recent efforts of reducing this recalcitrance with transgenic techniques have been showing promise for ameliorating or even obviating the need for costly pretreatments that are otherwise required to remove lignin from cellulose and hemicelluloses. At the same time, genetic manipulations of lignin biosynthetic enzymes have sometimes yielded unforeseen consequences on lignin composition, thus raising the question of whether the current understanding of the pathway is indeed correct. To address this question systemically, we developed and applied a novel modeling approach that, instead of analyzing the pathway within a single target context, permits a comprehensive, simultaneous investigation of different datasets in wild type and transgenic plants. Specifically, the proposed approach combines static flux-based analysis with a Monte Carlo simulation in which very many randomly chosen sets of parameter values are evaluated against kinetic models of lignin biosynthesis in different stem internodes of wild type and lignin-modified alfalfa plants. In addition to four new postulates that address the reversibility of some key reactions, the modeling effort led to two novel postulates regarding the control of the lignin biosynthetic pathway. The first posits functionally independent pathways toward the synthesis of different lignin monomers, while the second postulate proposes a novel feedforward regulatory mechanism. Subsequent laboratory experiments have identified the signaling molecule salicylic acid as a potential mediator of the postulated control mechanism. Overall, the results demonstrate that mathematical modeling can be a valuable complement to conventional transgenic approaches and that it can provide biological insights that are otherwise difficult to obtain.

  15. Control of Copper Resistance and Inorganic Sulfur Metabolism by Paralogous Regulators in Staphylococcus aureus*

    Science.gov (United States)

    Grossoehme, Nicholas; Kehl-Fie, Thomas E.; Ma, Zhen; Adams, Keith W.; Cowart, Darin M.; Scott, Robert A.; Skaar, Eric P.; Giedroc, David P.

    2011-01-01

    All strains of Staphylococcus aureus encode a putative copper-sensitive operon repressor (CsoR) and one other CsoR-like protein of unknown function. We show here that NWMN_1991 encodes a bona fide Cu(I)-inducible CsoR of a genetically unlinked copA-copZ copper resistance operon in S. aureus strain Newman. In contrast, an unannotated open reading frame found between NWMN_0027 and NWMN_0026 (denoted NWMN_0026.5) encodes a CsoR-like regulator that represses expression of adjacent genes by binding specifically to a pair of canonical operator sites positioned in the NWMN_0027–0026.5 intergenic region. Inspection of these regulated genes suggests a role in assimilation of inorganic sulfur from thiosulfate and vectorial sulfur transfer, and we designate NWMN_0026.5 as CstR (CsoR-like sulfur transferase repressor). Expression analysis demonstrates that CsoR and CstR control their respective regulons in response to distinct stimuli with no overlap in vivo. Unlike CsoR, CstR does not form a stable complex with Cu(I); operator binding is instead inhibited by oxidation of the intersubunit cysteine pair to a mixture of disulfide and trisulfide linkages by a likely metabolite of thiosulfate assimilation, sulfite. CsoR is unreactive toward sulfite under the same conditions. We conclude that CsoR and CstR are paralogs in S. aureus that function in the same cytoplasm to control distinct physiological processes. PMID:21339296

  16. Control of copper resistance and inorganic sulfur metabolism by paralogous regulators in Staphylococcus aureus.

    Science.gov (United States)

    Grossoehme, Nicholas; Kehl-Fie, Thomas E; Ma, Zhen; Adams, Keith W; Cowart, Darin M; Scott, Robert A; Skaar, Eric P; Giedroc, David P

    2011-04-15

    All strains of Staphylococcus aureus encode a putative copper-sensitive operon repressor (CsoR) and one other CsoR-like protein of unknown function. We show here that NWMN_1991 encodes a bona fide Cu(I)-inducible CsoR of a genetically unlinked copA-copZ copper resistance operon in S. aureus strain Newman. In contrast, an unannotated open reading frame found between NWMN_0027 and NWMN_0026 (denoted NWMN_0026.5) encodes a CsoR-like regulator that represses expression of adjacent genes by binding specifically to a pair of canonical operator sites positioned in the NWMN_0027-0026.5 intergenic region. Inspection of these regulated genes suggests a role in assimilation of inorganic sulfur from thiosulfate and vectorial sulfur transfer, and we designate NWMN_0026.5 as CstR (CsoR-like sulfur transferase repressor). Expression analysis demonstrates that CsoR and CstR control their respective regulons in response to distinct stimuli with no overlap in vivo. Unlike CsoR, CstR does not form a stable complex with Cu(I); operator binding is instead inhibited by oxidation of the intersubunit cysteine pair to a mixture of disulfide and trisulfide linkages by a likely metabolite of thiosulfate assimilation, sulfite. CsoR is unreactive toward sulfite under the same conditions. We conclude that CsoR and CstR are paralogs in S. aureus that function in the same cytoplasm to control distinct physiological processes.

  17. Paradoxes around good governance

    NARCIS (Netherlands)

    A.G. Dijkstra (Geske)

    2013-01-01

    textabstract Good governance is not a new concept Ambrogio Lorenzetti made his frescoes on good and bad governance already in the years 1338-1340 They can be viewed in the Palazzo Publicco on one of the most beautiful squares of the world, the Piazza del Campo in Siena, Italy I assume many of you

  18. "Act in Good Faith."

    Science.gov (United States)

    McKay, Robert B.

    1979-01-01

    It is argued that the Supreme Court's Bakke decision overturning the University of California's minority admissions program is good for those who favor affirmative action programs in higher education. The Supreme Court gives wide latitude for devising programs that take race and ethnic background into account if colleges are acting in good faith.…</