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Sample records for calcium metabolism disorders

  1. [Aging and homeostasis. Management of disorders in bone and calcium metabolism associated with ageing.

    PubMed

    Takeuchi, Yasuhiro

    Disorders in bone and calcium metabolism associated with aging are based on secondary hyperparathyroidism due to impaired intestinal calcium absorption caused by insufficient vitamin D actions and augmented bone resorption due to sex hormone deficiency. Both of them are involved in the development of osteoporosis that increases risk of fractures. Therefore, the most important thing for management of disorders in bone and calcium metabolism associated with aging is to prevent fractures with appropriate drugs for osteoporosis.

  2. Disorders of calcium, phosphorus, and magnesium metabolism in the neonate

    USDA-ARS?s Scientific Manuscript database

    Approximately 98% of the calcium, 80% of the phosphorus, and 65% of the magnesium in the body are in the skeleton. These elements, often referred to as the "bone minerals" are also constituents of the intracellular and extracellular spaces. The metabolism of these bone minerals and mineralization of...

  3. Calcium metabolism in birds.

    PubMed

    de Matos, Ricardo

    2008-01-01

    Calcium is one of the most important plasma constituents in mammals and birds. It provides structural strength and support (bones and eggshell) and plays vital roles in many of the biochemical reactions in the body. The control of calcium metabolism in birds is highly efficient and closely regulated in a number of tissues, primarily parathyroid gland, intestine, kidney, and bone. The hormones with the greatest involvement in calcium regulation in birds are parathyroid hormone, 1,25-dihydroxyvitamin D(3) (calcitriol), and estrogen, with calcitonin playing a minor and uncertain role. The special characteristics of calcium metabolism in birds, mainly associated with egg production, are discussed, along with common clinical disorders secondary to derangements in calcium homeostasis.

  4. [Prevalence and quality of control of calcium and phosphorus metabolism disorders among Lithuanian hemodialysis patients in 2004 and 2005].

    PubMed

    Petrauskiene, Vaida; Ziginskiene, Edita; Kuzminskis, Vytautas; Burciuviene, Asta; Grazulis, Saulius; Sileikiene, Elvyra; Masalskiene, Jūrate; Juodeikiene, Laima; Tamosaitis, Donatas; Alisauskiene, Violeta

    2007-01-01

    The aim of the study was to determine the prevalence and quality of control of disorders of calcium and phosphorus metabolism among patients on hemodialysis in Lithuania during the period of 2004-2005 and to assess rarely used methods of treatment such as parathyroidectomy and administration of calcimimetics. All Lithuanian hemodialysis centers were visited, and data on disorders of calcium-phosphorus metabolism were collected in December 2004 and 2005. The quality of control was evaluated according to Kidney Disease Outcome Quality Initiative recommendations. According to Kidney Disease Outcome Quality Initiative guidelines, normal parathyroid hormone levels were found in 20.4% of hemodialysis patients in 2004 and 18.8% of hemodialysis patients in 2005; normal levels of phosphate were in 41.9% and 39.4%, respectively; normal levels of calcium were observed in 44.7% of patients in 2004 and in 42.3% of patients in 2005. In 2005 as compared to 2004, there were statistically significantly more patients with low parathyroid hormone level (39.9% and 45.8%, respectively, P<0.05). Only in 5.6% of patients in 2004 and 3.9% of patients in 2005, all four parameters of calcium-phosphate metabolism (calcium, phosphate, and of parathyroid hormone levels and calcium-phosphate product) were within the normal range. No parameters in the normal range were found in 17-20% of patients. The use of alfacalcidol significantly increased: 316 (30.8%) patients in 2004 and 388 (35.7%) patients in 2005 were treated with alfacalcidol (P<0.05). Alfacalcidol was prescribed for 16.5% of patients in 2004 and for 17% of patients in 2005, in whom parathyroid hormone level was below the normal range in the presence of hypercalcemia and hyperphosphatemia. The use of calcimimetics was considered rational in 142 (13.8%) patients in 2004 and 119 (10.9%) patients in 2005. According to the data of our study, parathyroidectomy was indicated in 19 (1.85%) patients in 2004 and 17 (1.56%) patients in 2005

  5. [Quantitative mineralogical analyzes of kidney stones and diagnosing metabolic disorders in female patients with calcium oxalate urolithiasis].

    PubMed

    Kustov, A V; Moryganov, M A; Strel'nikov, A I; Zhuravleva, N I; Airapetyan, A O

    2016-02-01

    To conduct a complex examination of female patients with calcium oxalate urolithiasis to detect metabolic disorders, leading to stone formation. The study was carried out using complex physical and chemical methods, including quantitative X-ray phase analysis of urinary stones, pH measurement, volumetry, urine and blood spectrophotometry. Quantitative mineralogical composition of stones, daily urine pH profile, daily urinary excretion of ions of calcium, magnesium, oxalate, phosphate, citrate and uric acid were determined in 20 female patients with calcium oxalate stones. We have shown that most of the stones comprised calcium oxalate monohydrate or mixtures of calcium oxalate dihydrate and hydroxyapatite. Among the identified abnormalities, the most frequent were hypocitraturia and hypercalciuria - 90 and 45%, respectively. Our findings revealed that the daily secretion of citrate and oxalate in patients older than 50 years was significantly lower than in younger patients. In conclusion, daily urinary citrate excretion should be measured in female patients with calcium oxalate stones. This is necessary both to determine the causes of stone formation, and to monitor the effectiveness of citrate therapy.

  6. [Changes of control of disorders of calcium and phosphorus metabolism in Lithuanian hemodialysis centers 1996-2003].

    PubMed

    Ziginskiene, Edita; Kuzminskis, Vytautas; Bumblyte, Inga Arūne; Kardauskaite, Zydrūne; Uogintaite, Jurgita

    2005-01-01

    The aim of the study was to evaluate the changes of the rate of disorders of calcium and phosphorus metabolism and their control in patients on hemodialysis (HD) in Lithuania in 1996-2003. Every December during this period we visited all HD centers of Lithuania and collected data on calcium-phosphorus metabolism in HD patients. 51.8% of HD patients in 1999 and 44.6% in 2003 had hyperphosphatemia (>1.8 mmol/l) (p<0.05). The mean phosphate concentration was 1.82+/-0.56 mmol/l in 2003 (p<0.05, comparing with 1.95+/-0.72 mmol/l in 1999 and 1.9+/-0.72 mmol/l in 2001). 7.1% of HD patients had hypocalcemia in 2003 and 7.8% hypercalcemia. Serum parathyroid hormone level was investigated only in 27.3% of HD patients in 1999 and 84.8% in 2003 (p<0.05). Use of alfacalcidol significantly decreased from 77.5% in 1998 to 29.4% in 2003, when the evaluation of serum parathyroid hormone increased (r=-0.911, p=0.03). Serum parathyroid hormone level was not analyzed for 59.8% of patients who used alfacalcidol and 59.4% of them had hyperphosphatemia in 1999 (6.3% and 32.9% in 2003, respectively; p<0.05). 10.7% of these patients had hypercalcemia in 2003. In summary, the correction of disorders of calcium and phosphorus metabolism in HD patients was insufficient but ameliorative. Monitoring of serum parathyroid hormone increased significantly during 1997-2003. The percentage of the precarious use of alfacalcidol decreased significantly when the evaluation of serum parathyroid hormone level became regular.

  7. Use of diphosphonates to correct disorders in calcium metabolism and mineral composition of bone tissue with 60-day hypokinesia in rats

    NASA Technical Reports Server (NTRS)

    Morukov, B. V.; Zaychik, V. YE.; Ivanov, V. M.; Orlov, O. I.

    1988-01-01

    Compounds of the diphosphonate group suppress bone resorption and bone tissue metabolism, from which it was assumed that they can be used for the prevention of osteoporosis and disorders of calcium homeostasis in humans during space flight. Two compounds of this group were used for preventive purposes in 60 day hypokinesia in rats. The results showed that diphosphonates have a marked effect on calcium metabolism and the condition of the bone tissues under conditions of long term hypokinesia: they reduce the content of ionized calcium in blood, delay the loss of calcium and phosphorus by the bone tissue, and to a considerable degree prevent reduction of bone density. This confirms the possibility of using compounds of this group for correcting and preventing changes of bone tissue and mineral metabolism during long term hypokinesia.

  8. Diuretics and disorders of calcium homeostasis.

    PubMed

    Grieff, Marvin; Bushinsky, David A

    2011-11-01

    Diuretics commonly are administered in disorders of sodium balance. Loop diuretics inhibit the Na-K-2Cl transporter and also increase calcium excretion. They are often used in the treatment of hypercalcemia. Thiazide diuretics block the thiazide-sensitive NaCl transporter in the distal convoluted tubule, and can decrease calcium excretion. They are often used in the treatment of nephrolithiasis. Carbonic anhydrase inhibitors decrease bicarbonate absorption and the resultant metabolic acidosis can increase calcium excretion. Their use can promote nephrocalcinosis and nephrolithiasis. This review will address the use of diuretics on disorders of calcium homeostasis. Copyright © 2011 Elsevier Inc. All rights reserved.

  9. Plasma concentrations of parathyroid hormone-related protein in dogs with potential disorders of calcium metabolism.

    PubMed

    Mellanby, R J; Craig, R; Evans, H; Herrtage, M E

    2006-12-16

    The plasma concentrations of total calcium, ionised calcium, albumin, parathyroid hormone and parathyroid hormone-related protein (PTHrp) were measured in 25 dogs with lymphoma, nine dogs with primary hyperparathyroidism and seven dogs with adenocarcinoma of the apocrine gland of the anal sac. Plasma total calcium, ionised calcium, albumin and parathyroid hormone-related protein were measured in 18 clinically normal control dogs. The concentration of PTHrp was high in 12 of the 14 dogs that were hypercalcaemic because of an underlying malignancy but was within the reference range in all the control dogs, in the 17 normocalcaemic dogs with lymphoma and in the seven dogs which were hypercalcaemic because of a parathyroid adenoma.

  10. [Familial hypercalcemia and hypophosphatemia: importance in differential diagnosis of disorders in calcium-phosphate metabolism].

    PubMed

    Zofková, I

    2010-05-01

    Hypercalcemia and hypophosphatemia are symptoms of two relatively rare hereditary diseases and are extraordinarily important from the standpoint of the differential diagnosis. Mutation in calcium sensing receptor gene (CaSR) clinically manifests as familial hypocalciuric hypercalcemia (FHH) or as the much more serious neonatal hyperparathyreosis. Hypercalciuric hypocalcemia is extremely rare. Prognosis for the most frequent mutations in the CaSR gene FHH is considered benign; nevertheless, if overlooked it can lead to an incorrect diagnosis of primary hyperparathyreosis, which has a fundamentally different prognosis and treatment. Familial hypophosphatemia sometimes occurs as hereditary rickets, which is a consequence of insufficient production of vitamin D-hormone or abnormal function of vitamin D receptors (VDR). The disease manifests as X-linked dominant hypophosphatemic rickets or autosomal dominant hypophosphatemic rickets. Autosomal recessive form is very rare. Oncogenic hypophosphatemia should be excluded in differential diagnosis. In this review the issues of pathogenesis, differential diagnosis and treatment of FHH and hypophosphatemic rickets are discussed.

  11. Carbohydrate Metabolism Disorders

    MedlinePlus

    Metabolism is the process your body uses to make energy from the food you eat. Food is ... disorder, something goes wrong with this process. Carbohydrate metabolism disorders are a group of metabolic disorders. Normally ...

  12. Calcium and Bone Metabolism Indices.

    PubMed

    Song, Lu

    2017-01-01

    Calcium and inorganic phosphate are of critical importance for many body functions, thus the regulations of their plasma concentrations are tightly controlled by the concerted actions of reabsorption/excretion in the kidney, absorption in the intestines, and exchange from bone, the major reservoir for calcium and phosphate in the body. Parathyroid hormone (PTH) and 1,25-dihydroxyvitamin D (1,25(OH) 2 D) control calcium homeostasis, whereas PTH, 1,25(OH) 2 D, and bone-derived fibroblast growth factor 23 (FGF 23) control phosphate homeostasis. Hypoparathyroidism can cause hypocalcemia and hyperphosphatemia, whereas deficient vitamin D actions can cause osteomalacia in adults and rickets in children. Hyperparathyroidism, alternatively, can cause hypercalcemia and hypophosphatemia. Laboratory tests of calcium, phosphate, PTH, and 25-hydroxyvitamin D are very useful in the diagnosis of abnormalities associated with calcium and/or phosphate metabolisms. Bone is constantly remodeled throughout life in response to mechanical stress and a need for calcium in extracellular fluids. Metabolic bone diseases such as osteoporosis, osteomalacia in adults or rickets in children, and renal osteodystrophy develop when bone resorption exceeds bone formation. Bone turnover markers (BTM) such as serum N-terminal propeptide of type I procollagen (P1NP) and C-terminal collagen cross-link (CTX) may be useful in predicting future fracture risk or monitoring the response to anti-resorptive therapy. There is a need to standardize sample collection protocols because certain BTMs exhibit large circadian variations and tend to be influenced by food intakes. In the United States, a project to standardize BTM sample collection protocols and to establish the reference intervals for serum P1NP and serum CTX is ongoing. We anticipate the outcome of this project to shine lights on the standardization of BTM assays, sample collection protocols, reference intervals in relation to age, sex, and ethnic

  13. Adjustment of ionized calcium concentration for serum pH is not a valid marker of calcium homeostasis: implications for identifying individuals at risk of calcium metabolic disorders.

    PubMed

    Lam, Virginie; Dhaliwal, Satvinder S; Mamo, John C

    2013-05-01

    Ionized calcium (iCa) is the biologically active form of this micronutrient. Serum determination of iCa is measured via ion-electrode potentiometry (IEP) and reporting iCa relative to pH 7.4 is normally utilized to avoid the potential confounding effects of ex vivo changes to serum pH. Adjustment of iCa for pH has not been adequately justified. In this study, utilizing carefully standardized protocols for blood collection, the preparation of serum and controlling time of collection-to-analysis, we determined serum iCa and pH utilizing an IEP-analyser hosted at an accredited diagnostic laboratory. Regression analysis of unadjusted-iCa (iCa(raw)) concentration versus pH was described by linear regression and accounted for 37% of serum iCa(raw) variability. iCa(raw) was then expressed at pH 7.4 by either adjusting iCa(raw) based on the linear regression equation describing the association of iCa with serum pH (iCa(regr)) or using IEP coded published normative equations (iCa(pub)). iCa(regr) was comparable to iCa(raw), indicating that blood collection and processing methodologies were sound. However, iCa(pub) yielded values that were significantly lower than iCa(raw). iCa(pub) did not identify 15% subjects who had greater than desirable serum concentration of iCa based on iCa(raw). Sixty percent of subjects with low levels of iCa(raw) were also not detected by iCa(pub). Determination of the kappa value measure of agreement for iCa(raw) versus iCa(pub) showed relatively poor concordance (κ = 0.42). With simple protocols that avoid sampling artefacts, expressing iCa(raw) is likely to be a more valid and physiologically relevant marker of calcium homeostasis than is iCa(pub).

  14. Calcium metabolism and cardiovascular function after spaceflight

    NASA Technical Reports Server (NTRS)

    Hatton, Daniel C.; Yue, Qi; Dierickx, Jacqueline; Roullet, Chantal; Otsuka, Keiichi; Watanabe, Mitsuaki; Coste, Sarah; Roullet, Jean Baptiste; Phanouvang, Thongchan; Orwoll, Eric; hide

    2002-01-01

    To determine the influence of dietary calcium on spaceflight-induced alterations in calcium metabolism and blood pressure (BP), 9-wk-old spontaneously hypertensive rats, fed either high- (2%) or low-calcium (0.02%) diets, were flown on an 18-day shuttle flight. On landing, flight animals had increased ionized calcium (P < 0.001), elevated parathyroid hormone levels (P < 0.001), reduced calcitonin levels (P < 0.05), unchanged 1,25(OH)(2)D(3) levels, and elevated skull (P < 0.01) and reduced femur bone mineral density. Basal and thrombin-stimulated platelet free calcium (intracellular calcium concentration) were also reduced (P < 0.05). There was a tendency for indirect systolic BP to be reduced in conscious flight animals (P = 0.057). However, mean arterial pressure was elevated (P < 0.001) after anesthesia. Dietary calcium altered all aspects of calcium metabolism (P < 0.001), as well as BP (P < 0.001), but the only interaction with flight was a relatively greater increase in ionized calcium in flight animals fed low- compared with high-calcium diets (P < 0.05). The results indicate that 1) flight-induced disruptions of calcium metabolism are relatively impervious to dietary calcium in the short term, 2) increased ionized calcium did not normalize low-calcium-induced elevations of BP, and 3) parathyroid hormone was paradoxically increased in the high-calcium-fed flight animals after landing.

  15. Calcium metabolism in health and disease.

    PubMed

    Peacock, Munro

    2010-01-01

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

  16. Physiology of Calcium and Phosphate Metabolism: 1980 Refresher Course, Syllabus.

    ERIC Educational Resources Information Center

    Knox, Franklyn G., Ed.

    1980-01-01

    This syllabus reviews information concerning calcium and phosphate regulation. Topics of interest include the following: calcium metabolism, phosphorus metabolism, bone, parathyroid hormone, calcitonin, and vitamin D. (CS)

  17. Disorders of Amino Acid Metabolism

    MedlinePlus

    ... Drugs Ear, Nose, and Throat Disorders Eye Disorders Fundamentals Heart and Blood Vessel Disorders Hormonal and Metabolic ... Drugs Ear, Nose, and Throat Disorders Eye Disorders Fundamentals Heart and Blood Vessel Disorders Hormonal and Metabolic ...

  18. Endocrine causes of calcium disorders.

    PubMed

    Greco, Deborah S

    2012-11-01

    Endocrine diseases that may cause hypercalcemia and hypocalcemia include hyperparathyroidism, hypoparathyroidism, thyroid disorders, hyperadrenocorticism, hypoadrenocorticism, and less commonly pheochromocytoma and multiple endocrine neoplasias. The differential diagnosis of hypercalcemia may include malignancy (lymphoma, anal sac carcinoma, and squamous cell carcinoma), hyperparathyroidism, vitamin D intoxication, chronic renal disease, hypoadrenocorticism, granulomatous disorders, osteolysis, or spurious causes. Hypocalcemia may be caused by puerperal tetany, pancreatitis, intestinal malabsorption, ethlyene glycol intoxication, acute renal failure, hypopararthyroidism, hypovitaminosis D, hypomagnesemia, and low albumin. This article focuses on the endocrine causes of calcium imbalance and provides diagnostic and therapeutic guidelines for identifying the cause of hypercalcemia and hypocalcemia in veterinary patients. Copyright © 2012 Elsevier Inc. All rights reserved.

  19. Calcitonin control of calcium metabolism during weightlessness

    NASA Technical Reports Server (NTRS)

    Soliman, Karam F. A.

    1993-01-01

    The main objective of this proposal is to elucidate calcitonin role in calcium homeostasis during weightlessness. In this investigation our objectives are to study: the effect of weightlessness on thyroid and serum calcitonin, the effect of weightlessness on the circadian variation of calcitonin in serum and the thyroid gland, the role of light as zeitgeber for calcitonin circadian rhythm, the circadian pattern of thyroid sensitivity to release calcitonin in response to calcium load, and the role of serotonin and norepinephrine in the control of calcitonin release. The main objective of this research/proposal is to establish the role of calcitonin in calcium metabolism during weightlessness condition. Understanding the mechanism of these abnormalities will help in developing therapeutic means to counter calcium imbalance in spaceflights.

  20. Calcium and bone metabolism during space flight

    NASA Technical Reports Server (NTRS)

    Smith, Scott M.; Heer, Martina

    2002-01-01

    Weightlessness induces bone loss. Understanding the nature of this loss and developing means to counteract it are significant challenges to potential human exploration missions. This article reviews the existing information from studies of bone and calcium metabolism conducted during space flight. It also highlights areas where nutrition may play a specific role in this bone loss, and where countermeasures may be developed to mitigate that loss.

  1. Metabolism Disrupting Chemicals and Metabolic Disorders

    PubMed Central

    Heindel, Jerrold J.; Blumberg, Bruce; Cave, Mathew; Machtinger, Ronit; Mantovani, Alberto; Mendez, Michelle A.; Nadal, Angel; Palanza, Paola; Panzica, Giancarlo; Sargis, Robert; Vandenberg, Laura N.; Saal, Frederick vom

    2016-01-01

    The recent epidemics of metabolic diseases, obesity, type 2 diabetes(T2D), liver lipid disorders and metabolic syndrome have largely been attributed to genetic background and changes in diet, exercise and aging. However, there is now considerable evidence that other environmental factors may contribute to the rapid increase in the incidence of these metabolic diseases. This review will examine changes to the incidence of obesity, T2D and non-alcoholic fatty liver disease (NAFLD), the contribution of genetics to these disorders and describe the role of the endocrine system in these metabolic disorders. It will then specifically focus on the role of endocrine disrupting chemicals (EDCs) in the etiology of obesity, T2D and NAFLD while finally integrating the information on EDCs on multiple metabolic disorders that could lead to metabolic syndrome. We will specifically examine evidence linking EDC exposures during critical periods of development with metabolic diseases that manifest later in life and across generations. PMID:27760374

  2. Disorders of bone and bone mineral metabolism.

    PubMed

    Komoroski, Monica; Azad, Nasrin; Camacho, Pauline

    2014-01-01

    Metabolic bone disorders are very common in the general population and untreated, they can cause a variety of neurologic symptoms. These diseases include osteoporosis, vitamin D deficiency, Paget's disease, and alterations in calcium, phosphorus, and magnesium metabolism. Diagnosis is made through analysis of metabolic bone blood chemistries as well as radiologic studies such as dual energy X-ray absorptiometry (DXA) scans, bone scans, and X-rays. Treatment options have advanced significantly in the past decade for osteoporosis and Paget's disease and mainly include antiresorptive therapy. New recommendations for treatment of primary hyperparathyroidism are discussed as well as therapy for calcium, phosphorus, and mineral disorders. © 2014 Elsevier B.V. All rights reserved.

  3. Calcium and Bone Metabolism During Spaceflight

    NASA Technical Reports Server (NTRS)

    Smith, Scott M.

    2002-01-01

    The ability to understand and counteract weightlessness-induced bone loss will be critical for crew health and safety during and after space station or exploration missions lasting months or years, respectively. Until its deorbit in 2001 , the Mir Space Station provided a valuable platform for long-duration space missions and life sciences research. Long-duration flights are critical for studying bone loss, as the 2- to 3-week Space Shuttle flights are not long enough to detect changes in bone mass. This review will describe human spaceflight data, focusing on biochemical surrogates of bone and calcium metabolism. This subject has been reviewed previously. 1-

  4. Inflammation and metabolic disorders.

    PubMed

    Navab, Mohamad; Gharavi, Nima; Watson, Andrew D

    2008-07-01

    Poor nutrition, overweight and obesity have increasingly become a public health concern as they affect many metabolic disorders, including heart disease, diabetes, digestive system disorders, and renal failure. Study of the effects of life style including healthy nutrition will help further elucidate the mechanisms involved in the adverse effects of poor nutrition. Unhealthy life style including poor nutrition can result in imbalance in our oxidation/redox systems. Lipids can undergo oxidative modification by lipoxygenases, cyclooxygenases, myeloperoxidase, and other enzymes. Oxidized phospholipids can induce inflammatory molecules in the liver and other organs. This can contribute to inflammation, leading to coronary heart disease, stroke, renal failure, inflammatory bowl disease, metabolic syndrome, bone and joint disorders, and even certain types of cancer. Our antioxidant and antiinflammatory defense mechanisms contribute to a balance between the stimulators and the inhibitors of inflammation. Beyond a point, however, these systems might be overwhelmed and eventually fail. High-density lipoprotein is a potent inhibitor of the formation of toxic oxidized lipids. High-density lipoprotein is also an effective system for stimulating the genes whose products are active in the removal, inactivation, and elimination of toxic lipids. Supporting the high-density lipoprotein function should help maintain the balance in these systems. It is hoped that the present report would elucidate some of the ongoing work toward this goal.

  5. Effects of dietary bread crust Maillard reaction products on calcium and bone metabolism in rats.

    PubMed

    Roncero-Ramos, Irene; Delgado-Andrade, Cristina; Haro, Ana; Ruiz-Roca, Beatriz; Morales, Francisco J; Navarro, María Pilar

    2013-06-01

    Maillard reaction products (MRP) consumption has been related with the development of bone degenerative disorders, probably linked to changes in calcium metabolism. We aimed to investigate the effects of MRP intake from bread crust on calcium balance and its distribution, and bone metabolism. During 88 days, rats were fed control diet or diets containing bread crust as source of MRP, or its soluble high molecular weight, soluble low molecular weight or insoluble fractions (bread crust, HMW, LMW and insoluble diets, respectively). In the final week, a calcium balance was performed, then animals were sacrified and some organs removed to analyse calcium levels. A second balance was carried out throughout the experimental period to calculate global calcium retention. Biochemical parameters and bone metabolism markers were measured in serum or urine. Global calcium bioavailability was unmodified by consumption of bread crust or its isolate fractions, corroborating the previously described low affinity of MRP to bind calcium. Despite this, a higher calcium concentration was found in femur due to smaller bones having a lower relative density. The isolate consumption of the fractions altered some bone markers, reflecting a situation of increased bone resorption or higher turnover; this did not take place in the animals fed the bread crust diet. Thus, the bread crust intake does not affect negatively calcium bioavailability and bone metabolism.

  6. Bone and Calcium Metabolism During Space Flight

    NASA Technical Reports Server (NTRS)

    Smith, Scott M.

    2004-01-01

    Understanding bone loss during space flight is one of the most critical challenges for maintaining astronaut health on space exploration missions. Flight and ground-based studies have been conducted to better understand the nature and mechanisms of weightlessness-induced bone loss, and to identify a means to counteract the loss. Maintenance of bone health requires a balance between bone formation and bone resorption. Early space research identified bone loss as a critical health issue, but could not provide a distinction between the bone formation and breakdown processes. The recent identification of collagen crosslinks as markers of bone resorption has made possible a clear understanding that a decrease in bone resorption is an important effect of space flight, with bone formation being unchanged or only slightly decreased. Calcium regulatory factors have also been studied, in an attempt to understand their role in bone loss. The lack of ultraviolet light exposure and insufficient dietary sources of vitamin D often lead to reduced vitamin D stores on long-duration flights. Serum parathyroid hormone (PTH) concentrations are decreased during flight compared to before flight, although small subject numbers often make this hard to document statistically. As expected, reduced PTH concentrations are accompanied by reduced 1,25-dihydroxyvitamin D concentrations. Calcium kinetic studies during space flight confirm and extend the information gained from biochemical markers of bone metabolism. Calcium kinetic studies demonstrate that bone resorption is increased, bone formation is unchanged or decreased, and dietary calcium absorption is reduced during space flight. Evaluations have also been conducted of countermeasures, including dietary, exercise, and pharmacological treatments. In recent studies, many potential countermeasures show promise at mitigating bone loss in ground-based analogs of weightlessness (e.g., bed rest), but require further ground and flight testing to

  7. The effect of variable calcium and very low calcium diets on human calcium metabolism. Ph.D. Thesis. Final Report

    NASA Technical Reports Server (NTRS)

    Chu, J.

    1971-01-01

    The effects of a very low calcium diet, with variable high and low protein intake, on the dynamics of calcium metabolism and the mechanism of calciuretics, are examined. The experiment, using male subjects, was designed to study the role of intestinal calcium absorption on urinary calcium excretion, and the rate of production of endogeneously secreted calcium in the gastrointestinal tract. The study showed an average of 70% fractional absorption rate during very low calcium intake, and that a decrease in renal tubular reabsorption of calcium is responsible for calciuretic effects of high protein intake. The study also indicates that there is a tendency to develop osteoporosis after long periods of low calcium intake, especially with a concurrent high protein intake.

  8. Gut Microbiota and Metabolic Disorders

    PubMed Central

    Hur, Kyu Yeon

    2015-01-01

    Gut microbiota plays critical physiological roles in the energy extraction and in the control of local or systemic immunity. Gut microbiota and its disturbance also appear to be involved in the pathogenesis of diverse diseases including metabolic disorders, gastrointestinal diseases, cancer, etc. In the metabolic point of view, gut microbiota can modulate lipid accumulation, lipopolysaccharide content and the production of short-chain fatty acids that affect food intake, inflammatory tone, or insulin signaling. Several strategies have been developed to change gut microbiota such as prebiotics, probiotics, certain antidiabetic drugs or fecal microbiota transplantation, which have diverse effects on body metabolism and on the development of metabolic disorders. PMID:26124989

  9. Inherited metabolic disorders in Thailand.

    PubMed

    Wasant, Pornswan; Svasti, Jisnuson; Srisomsap, Chantragan; Liammongkolkul, Somporn

    2002-08-01

    The study of inborn errors of metabolism (IEM) in Thailand is in its infancy. The majority are clinically diagnosed since there are only a handful of clinicians and scientists with expertise in inherited metabolic disorders, shortage of well-equipped laboratory facilities and lack of governmental financial support. Genetic metabolic disorders are usually not considered a priority due to prevalence of infectious diseases and congenital infections. From a retrospective study at the Medical Genetics Unit, Department of Pediatrics, Siriraj Hospital; estimated pediatrics patients with suspected IEM were approximately 2-3 per cent of the total pediatric admissions of over 5,000 annually. After more than 10 years of research and accumulated clinical experiences, a genetic metabolic center is being established in collaboration with expert laboratories both in Bangkok (Chulabhorn Research Institute) and abroad (Japan and the United States). Numerous inherited metabolic disorders were identified--carbohydrate, amino acids, organic acids, mitochondrial fatty acid oxidation, peroxisomal, mucopolysaccharidoses etc. This report includes the establishment of genetic metabolic center in Thailand, research and pilot studies in newborn screening in Thailand and a multicenter study from 5 institutions (Children's National Center, King Chulalongkorn Memorial Hospital, Pramongkutklao Hospital, Ramathibodi and Siriraj Hospitals). Inherited metabolic disorders reported are fructose-1,6-bisphosphatase deficiency, phenylketonuria, homocystinuria, nonketotic hyperglycinemia, urea cycle defect (arginino succinate lyase deficiency, argininosuccinate synthetase deficiency), Menkes disease, propionic acidemia and mucopolysaccharidoses (Hurler, Hurler-Scheie).

  10. In vivo calcium metabolism by IRMS

    USDA-ARS?s Scientific Manuscript database

    Public policy initiatives related to enhancing the health of populations, increasingly seek to identify meaningful biological outcomes on which to determine age-related nutritional requirements. For calcium, the primary outcome of interest is the availability of calcium in the diet for bone formatio...

  11. Acidosis and Urinary Calcium Excretion: Insights from Genetic Disorders

    PubMed Central

    Cordat, Emmanuelle; Chambrey, Régine; Dimke, Henrik; Eladari, Dominique

    2016-01-01

    Metabolic acidosis is associated with increased urinary calcium excretion and related sequelae, including nephrocalcinosis and nephrolithiasis. The increased urinary calcium excretion induced by metabolic acidosis predominantly results from increased mobilization of calcium out of bone and inhibition of calcium transport processes within the renal tubule. The mechanisms whereby acid alters the integrity and stability of bone have been examined extensively in the published literature. Here, after briefly reviewing this literature, we consider the effects of acid on calcium transport in the renal tubule and then discuss why not all gene defects that cause renal tubular acidosis are associated with hypercalciuria and nephrocalcinosis. PMID:27468975

  12. [Metabolic disorders as paraneoplastic syndromes].

    PubMed

    Krug, S; Michl, P

    2018-02-01

    Paraneoplastic syndromes are characterized by the tumor-induced release of peptide hormones and/or the initiation of immune phenomena, which elicit clinical changes and alterations in laboratory parameters independent of the tumor size and spread. In addition to neurological, endocrinal and rheumatological phenotypes, metabolic alterations play a special role in the clinical routine as they commonly present with acute symptoms in an emergency situation and necessitate immediate diagnosis and prompt initiation of treatment. Metabolic alterations within the framework of malignant diseases should be treated in a multidisciplinary team and it is often necessary to perform monitoring and treatment in an intensive care unit. This article focuses on the diagnostic and therapeutic options for metabolic disorders due to paraneoplastic syndromes, such as hypercalcemia, hypocalcemia, hyperglycemia, hypoglycemia and a special variant of tumor-induced metabolic disorders due to tumor lysis syndrome.

  13. [The peculiarities of calcium metabolism regulation in different periods of growth and development].

    PubMed

    Moĭsa, S S; Nozdrachev, A D

    2014-01-01

    The review contains literature data about calcium metabolism regulation in different periods of growth and development. The analyses of retrospective and current sources of information about the regulation of calcium homeostasis under the theory of functional systems, the regulation of calcium metabolism in prenatal and postnatal periods of the development, the significance of calcium metabolism disturbances in the development of pathological conditions were showed.

  14. [The antioxidant prevention of disorders in calcium ion metabolism under the action of glutamate on the synaptosomes of the rat cerebral cortex].

    PubMed

    Avrova, N F; Shestak, K I; Zakharova, I O; Sokolova, T V; Tiurina, Iu Iu; Tiurin, V A

    1999-04-01

    An increase of intracellular calcium ion concentration and of the 45Ca2+ entry, a decrease in Na+,K(+)-ATPase activity, and activation of Na+/Ca2+ exchange were shown to be initiated by glutamate in the rat brain cortex synaptosomes. These effects could be prevented with antagonists and blocking agents of the NMDA receptors. Pre-incubation of the synaptosomes with alpha-tocopherol, superoxide dismutase, and ganglioside GM1 was shown to normalise [45Ca2+], the rate of 45Ca2+ entry, and the activity of Na+,K(+)-ATPase in the synaptosomes. The data obtained suggest that calcium ions entering the brain cortex neurones via the NMDA receptors in presence of excessive glutamate, trigger activation of free radical reactions damaging the neurones in ischemia, cerebral lesions, and other pathological conditions.

  15. The Function of the Mitochondrial Calcium Uniporter in Neurodegenerative Disorders

    PubMed Central

    Liao, Yajin; Dong, Yuan; Cheng, Jinbo

    2017-01-01

    The mitochondrial calcium uniporter (MCU)—a calcium uniporter on the inner membrane of mitochondria—controls the mitochondrial calcium uptake in normal and abnormal situations. Mitochondrial calcium is essential for the production of adenosine triphosphate (ATP); however, excessive calcium will induce mitochondrial dysfunction. Calcium homeostasis disruption and mitochondrial dysfunction is observed in many neurodegenerative disorders. However, the role and regulatory mechanism of the MCU in the development of these diseases are obscure. In this review, we summarize the role of the MCU in controlling oxidative stress-elevated mitochondrial calcium and its function in neurodegenerative disorders. Inhibition of the MCU signaling pathway might be a new target for the treatment of neurodegenerative disorders. PMID:28208618

  16. Mammary-Specific Ablation of the Calcium-Sensing Receptor During Lactation Alters Maternal Calcium Metabolism, Milk Calcium Transport, and Neonatal Calcium Accrual

    PubMed Central

    Mamillapalli, Ramanaiah; VanHouten, Joshua; Dann, Pamela; Bikle, Daniel; Chang, Wenhan; Brown, Edward

    2013-01-01

    To meet the demands for milk calcium, the lactating mother adjusts systemic calcium and bone metabolism by increasing dietary calcium intake, increasing bone resorption, and reducing renal calcium excretion. As part of this adaptation, the lactating mammary gland secretes PTHrP into the maternal circulation to increase bone turnover and mobilize skeletal calcium stores. Previous data have suggested that, during lactation, the breast relies on the calcium-sensing receptor (CaSR) to coordinate PTHrP secretion and milk calcium transport with calcium availability. To test this idea genetically, we bred BLG-Cre mice with CaSR-floxed mice to ablate the CaSR specifically from mammary epithelial cells only at the onset of lactation (CaSR-cKO mice). Loss of the CaSR in the lactating mammary gland did not disrupt alveolar differentiation or milk production. However, it did increase the secretion of PTHrP into milk and decreased the transport of calcium from the circulation into milk. CaSR-cKO mice did not show accelerated bone resorption, but they did have a decrease in bone formation. Loss of the mammary gland CaSR resulted in hypercalcemia, decreased PTH secretion, and increased renal calcium excretion in lactating mothers. Finally, loss of the mammary gland CaSR resulted in decreased calcium accrual by suckling neonates, likely due to the combination of increased milk PTHrP and decreased milk calcium. These results demonstrate that the mammary gland CaSR coordinates maternal bone and calcium metabolism, calcium transport into milk, and neonatal calcium accrual during lactation. PMID:23782944

  17. CALCIUM AND PHOSPHORUS METABOLISM IN OSTEOMALACIA

    PubMed Central

    Miles, Lee Monroe; Feng, Chih-Tung

    1925-01-01

    Osteomalacia is a diet deficiency disease of the same category as rickets. The deficiency is principally in the fat-soluble vitamine content of the diet, though there may be a calcium deficiency at the same time. The disease may be prevented by providing a diet rich in the fat-soluble vitamine content, and may be cured by adding the same to the diet. PMID:19868970

  18. Disorders of metal metabolism

    PubMed Central

    Ferreira, Carlos R.; Gahl, William A.

    2017-01-01

    Trace elements are chemical elements needed in minute amounts for normal physiology. Some of the physiologically relevant trace elements include iodine, copper, iron, manganese, zinc, selenium, cobalt and molybdenum. Of these, some are metals, and in particular, transition metals. The different electron shells of an atom carry different energy levels, with those closest to the nucleus being lowest in energy. The number of electrons in the outermost shell determines the reactivity of such an atom. The electron shells are divided in sub-shells, and in particular the third shell has s, p and d sub-shells. Transition metals are strictly defined as elements whose atom has an incomplete d sub-shell. This incomplete d sub-shell makes them prone to chemical reactions, particularly redox reactions. Transition metals of biologic importance include copper, iron, manganese, cobalt and molybdenum. Zinc is not a transition metal, since it has a complete d sub-shell. Selenium, on the other hand, is strictly speaking a nonmetal, although given its chemical properties between those of metals and nonmetals, it is sometimes considered a metalloid. In this review, we summarize the current knowledge on the inborn errors of metal and metalloid metabolism. PMID:29354481

  19. Metabolic disorders causing childhood ataxia.

    PubMed

    Parker, Colette C; Evans, Owen B

    2003-09-01

    Ataxia is a common neurologic finding in many disease processes of the nervous system, and has classically been associated with numerous metabolic disorders. An error of metabolism should be considered when the ataxia is either intermittent or progressive. Acute exacerbation or worsening after high protein ingestion, concurrent febrile illness, or other physical stress is also suggestive. A positive family history can be an important diagnostic clue. Progressive molecular and biochemical techniques are revolutionizing this area of medicine, and there has been rapid advancement in understanding of the disease processes.

  20. Effectiveness of using thyrocalcitonin for the prevention of a calcium metabolic disorder in the mineralized tissues of rabbits with 30 days hypokinesia

    NASA Technical Reports Server (NTRS)

    Volozhin, A. I.; Shashkov, V. S.; Dmitriyev, B. S.; Yegorov, B. B.; Lobachik, V. I.; Brishin, A. I.

    1980-01-01

    A 30 day hypokinesia in rabbits led to a considerable lag in weight gain for the skeletal bones, reduction in Ca45 uptake, and an increase in isotope resorption rate in the rapidly metabolized fraction of extremity bones. On the other hand, Ca45 content in the teeth and maxillae increased, which may be explained by redistribution of isotope among the various mineralized tissues. Injection of thyrocalcitonin (50 IU/day) produced a distinct normalizing effect on Ca45 uptake and resorption in the mineralized tissues of rabbits kept hypokinetic.

  1. Serum ionized calcium in dogs with chronic renal failure and metabolic acidosis.

    PubMed

    Kogika, Marcia M; Lustoza, Marcio D; Notomi, Marcia K; Wirthl, Vera A B F; Mirandola, Regina M S; Hagiwara, Mitika K

    2006-12-01

    Chronic renal failure (CRF) is a common disease in dogs, and many metabolic disorders can be observed, including metabolic acidosis and calcium and phosphorus disturbances. Acidosis may change the ionized calcium (i-Ca) fraction, usually increasing its concentration. In this study we evaluated the influence of acidosis on the serum concentration of i-Ca in dogs with CRF and metabolic acidosis. Dogs were studied in 2 groups: group I (control group = 40 clinically normal dogs) and group II (25 dogs with CRF and metabolic acidosis). Serum i-Ca was measured by an ion-selective electrode method; other biochemical analytes were measured using routine methods. The i-Ca concentration was significantly lower in dogs in group II than in group I; 56% of the dogs in group II were hypocalcemic. Hypocalcemia was observed in only 8% of dogs in group II when based on total calcium (t-Ca) concentration. No correlation between pH and i-Ca concentration was observed. A slight but significant correlation was detected between i-Ca and serum phosphorus concentration (r = -.284; P = .022), as well as between serum t-Ca and i-Ca concentration (r = .497; P < .0001). The i-Ca concentration in dogs with CRF and metabolic acidosis varied widely from that of t-Ca, showing the importance of determining the biologically active form of calcium. Metabolic acidosis did not influence the increase in i-Ca concentration, so other factors besides acidosis in CRF might alter the i-Ca fraction, such as hyperphosphatemia and other compounds that may form complexes with calcium.

  2. Effect of Microgravity on Bone Tissue and Calcium Metabolism

    NASA Technical Reports Server (NTRS)

    1997-01-01

    Session TA4 includes short reports concerning: (1) Human Bone Tissue Changes after Long-Term Space Flight: Phenomenology and Possible Mechanics; (2) Prediction of Femoral Neck Bone Mineral Density Change in Space; (3) Dietary Calcium in Space; (4) Calcium Metabolism During Extended-Duration Space Flight; (5) External Impact Loads on the Lower Extremity During Jumping in Simulated Microgravity and the Relationship to Internal Bone Strain; and (6) Bone Loss During Long Term Space Flight is Prevented by the Application of a Short Term Impulsive Mechanical Stimulus.

  3. Dietary protein, calcium metabolism, and skeletal homeostasis revisited.

    PubMed

    Kerstetter, Jane E; O'Brien, Kimberly O; Insogna, Karl L

    2003-09-01

    High dietary protein intakes are known to increase urinary calcium excretion and, if maintained, will result in sustained hypercalciuria. To date, the majority of calcium balance studies in humans have not detected an effect of dietary protein on intestinal calcium absorption or serum parathyroid hormone. Therefore, it is commonly concluded that the source of the excess urinary calcium is increased bone resorption. Recent studies from our laboratory indicate that alterations in dietary protein can, in fact, profoundly affect intestinal calcium absorption. In short-term dietary trials in healthy adults, we fixed calcium intake at 20 mmol/d while dietary protein was increased from 0.7 to 2.1 g/kg. Increasing dietary protein induced hypercalciuria in 20 women [from 3.4 +/- 0.3 ( +/- SE) during the low-protein to 5.4 +/- 0.4 mmol/d during the high-protein diet]. The increased dietary protein was accompanied by a significant increase in intestinal calcium absorption from 18.4 +/- 1.3% to 26.3 +/- 1.5% (as determined by dual stable isotopic methodology). Dietary protein intakes at and below 0.8 g/kg were associated with a probable reduction in intestinal calcium absorption sufficient to cause secondary hyperparathyroidism. The long-term consequences of these low-protein diet-induced changes in mineral metabolism are not known, but the diet could be detrimental to skeletal health. Of concern are several recent epidemiologic studies that demonstrate reduced bone density and increased rates of bone loss in individuals habitually consuming low-protein diets. Studies are needed to determine whether low protein intakes directly affect rates of bone resorption, bone formation, or both.

  4. [The fasting calcium/creatinine ratio in patients with calcium stones and the relation with hypercalciuria and phosphocalcium metabolism].

    PubMed

    Arrabal-Polo, Miguel Ángel; del Carmen Cano-García, María; Arrabal-Martín, Miguel

    2016-04-01

    To determine the importance of fasting calcium/creatinine ratio in patients with calcium stones and its relation with hypercalciuria and phospho-calcium metabolism. Cross-sectional study including 143 patients divided into two groups according to fasting calcium/creatinine. Group 1: 66 patients (calcium/ creatinine<0.11); Group 2: 77 patients (calcium/ creatinine>0.11). A comparative study is performed between groups including phospho-calcium metabolism parameters and excretion of urinary lithogenic markers. Linear correlation studying calciuria and fasting calcium/ creatinine was performed. SPSS 17.0 statistical analysis software was used, considering p≤0.05. It is noteworthy that group 2 had increased 24 h urine calcium excretion in comparison to group 1 (229.3 vs 158.1; p=0.0001) and calcium/citrate (0.47 vs 0.34; p=0.001). There is a positive and significant correlation between calcium levels in 24 h urine and fasting calcium/creatinine (R=0.455; p=0.0001) and a cutoff is set at 0.127 (sensitivity 72%, specificity 66%) to determine hypercalciuria (>260 mg in 24 h). Increased fasting calcium/creatinine determines increased 24 hours calcium excretion, although the sensitivity and specificity to determine hypercalciuria is not high.

  5. Calcium-phosphate metabolism in patients with multiple sclerosis.

    PubMed

    Kubicka-Baczyk, K; Labuz-Roszak, B; Pierzchala, K; Adamczyk-Sowa, M; Machowska-Majchrzak, A

    2015-06-01

    The purpose of this study was to evaluate the concentration of 25-hydroxycholecalciferol and parameters of calcium-phosphate metabolism at different periods of relapsing-remitting multiple sclerosis (RRMS). Forty-five patients, residents of Poland (49°-50°, N), were enrolled in the study, i.e. 15 immediately after the diagnosis of RRMS, 15 at the early stage and 15 at the advanced stage of RRMS. The results were compared to values obtained in 20 age- and sex-matched controls. Lower serum concentrations of 25-hydroxycholecalciferol and ionised calcium were found in patients compared to the control group. In patients with the disease duration of 5-6 years, concentrations of 25-hydroxycholecalciferol and ionised calcium were lower than in patients in the earlier period of RRMS. The inverse and clearer direction of changes was found in parathormone serum concentration in patients compared to the controls. In patients with a longer disease duration, a significantly lower 25-hydroxycholecalciferol concentration was found in female patients compared to male patients. In patients, more frequent 25-hydroxycholecalciferol and unsaturated fatty acids' supplementation was observed compared to the controls. In RRMS patients, calcium-phosphate metabolism is disturbed which increases during disease progression.

  6. Space-flight simulations of calcium metabolism using a mathematical model of calcium regulation

    NASA Technical Reports Server (NTRS)

    Brand, S. N.

    1985-01-01

    The results of a series of simulation studies of calcium matabolic changes which have been recorded during human exposure to bed rest and space flight are presented. Space flight and bed rest data demonstrate losses of total body calcium during exposure to hypogravic environments. These losses are evidenced by higher than normal rates of urine calcium excretion and by negative calcium balances. In addition, intestinal absorption rates and bone mineral content are assumed to decrease. The bed rest and space flight simulations were executed on a mathematical model of the calcium metabolic system. The purpose of the simulations is to theoretically test hypotheses and predict system responses which are occurring during given experimental stresses. In this case, hypogravity occurs through the comparison of simulation and experimental data and through the analysis of model structure and system responses. The model reliably simulates the responses of selected bed rest and space flight parameters. When experimental data are available, the simulated skeletal responses and regulatory factors involved in the responses agree with space flight data collected on rodents. In addition, areas within the model that need improvement are identified.

  7. Calcium, magnesium, and phosphorus metabolism in dogs given intravenous triacetin.

    PubMed

    Bailey, J W; Heath, H; Miles, J M

    1989-02-01

    Previous studies suggested that acetate in parenteral solutions may adversely affect mineral metabolism by causing sequestration of inorganic phosphate and calcium in the liver. In this study, triacetin, a short-chain triglyceride of acetate and a potential parenteral nutrient, was infused for 3 h at an isocaloric rate in mongrel dogs (n = 6) to test its effects on serum phosphorus, calcium, and magnesium metabolism. There was no change in serum P or Ca. The serum Mg concentration decreased from 0.7 +/- 0.03 to 0.57 +/- 0.03 mmol/L (p less than 0.001) by 90 min and remained at this level for the remainder of the study. The triacetin infusion did not influence fractional urinary Mg excretion; thus, the decrease in serum Mg was likely because of an increase in cellular transport of this cation. A short-chain triglyceride administered to dogs at a rate approximating resting energy expenditure has no demonstrable adverse effects on mineral metabolism.

  8. Effect of phosphorus and calcium on zinc metabolism in man

    SciTech Connect

    Spencer, H.; Kramer, L.; Lesniak, M.

    The effect of phosphorus on zinc metabolism was studied in adult men receiving different calcium intakes ranging from 200 to 2000 mg/day. The diet and urinary and fecal excretions were analyzed for Zn, P and Ca. Metabolic balances of these elements were determined for several weeks in each study phase. In control studies the dietary intake was 800 mg/day and in the experimental studies it was increased to 2000 mg/day by adding sodium glycerophosphate to the constant diet. The dietary Zn intake averaged 14.5 mg/day in the different studies. These studies have shown that increasing the P intake by amore » factor of 2.5, from 800 to 2000 mg/day, did not affect urinary or fecal Zn excretions nor the Zn balance. Similar results were obtained on increasing the Ca intake from 200 to 2000 mg/day.« less

  9. Metabolic consequences of sleep and circadian disorders

    PubMed Central

    Depner, Christopher M.; Stothard, Ellen R.; Wright, Kenneth P.

    2014-01-01

    Sleep and circadian rhythms modulate or control daily physiological patterns with importance for normal metabolic health. Sleep deficiencies associated with insufficient sleep schedules, insomnia with short-sleep duration, sleep apnea, narcolepsy, circadian misalignment, shift work, night eating syndrome and sleep-related eating disorder may all contribute to metabolic dysregulation. Sleep deficiencies and circadian disruption associated with metabolic dysregulation may contribute to weight gain, obesity, and type 2 diabetes potentially by altering timing and amount of food intake, disrupting energy balance, inflammation, impairing glucose tolerance and insulin sensitivity. Given the rapidly increasing prevalence of metabolic diseases, it is important to recognize the role of sleep and circadian disruption in the development, progression, and morbidity of metabolic disease. Some findings indicate sleep treatments and countermeasures improve metabolic health, but future clinical research investigating prevention and treatment of chronic metabolic disorders through treatment of sleep and circadian disruption is needed. PMID:24816752

  10. Metabolic consequences of sleep and circadian disorders.

    PubMed

    Depner, Christopher M; Stothard, Ellen R; Wright, Kenneth P

    2014-07-01

    Sleep and circadian rhythms modulate or control daily physiological patterns with importance for normal metabolic health. Sleep deficiencies associated with insufficient sleep schedules, insomnia with short-sleep duration, sleep apnea, narcolepsy, circadian misalignment, shift work, night eating syndrome, and sleep-related eating disorder may all contribute to metabolic dysregulation. Sleep deficiencies and circadian disruption associated with metabolic dysregulation may contribute to weight gain, obesity, and type 2 diabetes potentially by altering timing and amount of food intake, disrupting energy balance, inflammation, impairing glucose tolerance, and insulin sensitivity. Given the rapidly increasing prevalence of metabolic diseases, it is important to recognize the role of sleep and circadian disruption in the development, progression, and morbidity of metabolic disease. Some findings indicate sleep treatments and countermeasures improve metabolic health, but future clinical research investigating prevention and treatment of chronic metabolic disorders through treatment of sleep and circadian disruption is needed.

  11. Effect of low gravity on calcium metabolism and bone formation (L-7)

    NASA Technical Reports Server (NTRS)

    Suda, Tatsuo

    1993-01-01

    Recently, attention has been focused on the disorders of bone and calcium metabolism during space flight. The skeletal system has evolved on the Earth under 1-g. Space flights under low gravity appear to cause substantial changes in bone and calcium homeostasis of the animals adapted to 1-g. A space experiment for the First Materials Processing Test (FMPT) was proposed to examine the effects of low gravity on calcium metabolism and bone formation using chick embryos loaded in a space shuttle. This space experiment was proposed based on the following two experimental findings. First, it has been reported that bone density decreases significantly during prolonged space flight. The data obtained from the US Skylab and the U.S.S.R. Salyut-6 cosmonauts have also documented that the degree of bone loss is related to the duration of space flight. Second, the US-Soviet joints space experiment demonstrated that the decrease in bone density under low gravity appears to be due to the decrease in bone formation rather than the increase in bone resorption. The purpose of our space experiment is, therefore, to investigate further the mechanisms of bone growth under low gravity using fertilized chick embryos.

  12. Microglia energy metabolism in metabolic disorder.

    PubMed

    Kalsbeek, Martin J T; Mulder, Laurie; Yi, Chun-Xia

    2016-12-15

    Microglia are the resident macrophages of the CNS, and are in charge of maintaining a healthy microenvironment to ensure neuronal survival. Microglia carry out a non-stop patrol of the CNS, make contact with neurons and look for abnormalities, all of which requires a vast amount of energy. This non-signaling energy demand increases after activation by pathogens, neuronal damage or other kinds of stimulation. Of the three major energy substrates - glucose, fatty acids and glutamine - glucose is crucial for microglia survival and several glucose transporters are expressed to supply sufficient glucose influx. Fatty acids are another source of energy for microglia and have also been shown to strongly influence microglial immune activity. Glutamine, although possibly suitable for use as an energy substrate by microglia, has been shown to have neurotoxic effects when overloaded. Microglial fuel metabolism might be associated with microglial reactivity under different pathophysiological conditions and a microglial fuel switch may thus be the underlying cause of hypothalamic dysregulation, which is associated with obesity. Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.

  13. EFFECTS OF LINDANE AND LINURON ON CALCIUM METABOLISM, MORPHOMETRY, AND THE KIDNEY

    EPA Science Inventory

    The effects of lindane and linuron on calcium metabolism, bone morphometry and the kidney. xperiments were performed to investigate the effects of lindane and linuron on calcium metabolism, femur morphometry and nephrotoxicity. ong-Evans hooded rats were dosed daily for 10 weeks ...

  14. Neurologic disorders of mineral metabolism and parathyroid disease.

    PubMed

    Agrawal, Lily; Habib, Zeina; Emanuele, Nicholas V

    2014-01-01

    Disorders of mineral metabolism may cause neurologic manifestations of the central and peripheral nervous systems. This is because plasma calcium stabilizes excitable membranes in the nerve and muscle tissue, magnesium is predominantly intracellular and is required for activation of many intracellular enzymes, and extracellular magnesium affects synaptic transmission. This chapter reviews abnormalities in electrolytes and minerals which can be associated with several neuromuscular symptoms including neuromuscular irritability, mental status changes, cardiac and smooth muscle changes, etc. © 2014 Elsevier B.V. All rights reserved.

  15. Disordered amorphous calcium carbonate from direct precipitation

    DOE PAGES

    Farhadi Khouzani, Masoud; Chevrier, Daniel M.; Güttlein, Patricia; ...

    2015-06-01

    Amorphous calcium carbonate (ACC) is known to play a prominent role in biomineralization. Different studies on the structure of biogenic ACCs have illustrated that they can have distinct short-range orders. However, the origin of so-called proto-structures in synthetic and additive-free ACCs is not well understood. In the current work, ACC has been synthesised in iso-propanolic media by direct precipitation from ionic precursors, and analysed utilising a range of different techniques. The data suggest that this additive-free type of ACC does not resemble clear proto-structural motifs relating to any crystalline polymorph. This can be explained by the undefined pH value inmore » iso-propanolic media, and the virtually instantaneous precipitation. Altogether, this work suggests that aqueous systems and pathways involving pre-nucleation clusters are required for the generation of clear proto-structural features in ACC. Experiments on the ACC-to-crystalline transformation in solution with and without ethanol highlight that polymorph selection is under kinetic control, while the presence of ethanol can control dissolution re-crystallisation pathways.« less

  16. Taxonomy of rare genetic metabolic bone disorders.

    PubMed

    Masi, L; Agnusdei, D; Bilezikian, J; Chappard, D; Chapurlat, R; Cianferotti, L; Devolgelaer, J-P; El Maghraoui, A; Ferrari, S; Javaid, M K; Kaufman, J-M; Liberman, U A; Lyritis, G; Miller, P; Napoli, N; Roldan, E; Papapoulos, S; Watts, N B; Brandi, M L

    2015-10-01

    This article reports a taxonomic classification of rare skeletal diseases based on metabolic phenotypes. It was prepared by The Skeletal Rare Diseases Working Group of the International Osteoporosis Foundation (IOF) and includes 116 OMIM phenotypes with 86 affected genes. Rare skeletal metabolic diseases comprise a group of diseases commonly associated with severe clinical consequences. In recent years, the description of the clinical phenotypes and radiographic features of several genetic bone disorders was paralleled by the discovery of key molecular pathways involved in the regulation of bone and mineral metabolism. Including this information in the description and classification of rare skeletal diseases may improve the recognition and management of affected patients. IOF recognized this need and formed a Skeletal Rare Diseases Working Group (SRD-WG) of basic and clinical scientists who developed a taxonomy of rare skeletal diseases based on their metabolic pathogenesis. This taxonomy of rare genetic metabolic bone disorders (RGMBDs) comprises 116 OMIM phenotypes, with 86 affected genes related to bone and mineral homeostasis. The diseases were divided into four major groups, namely, disorders due to altered osteoclast, osteoblast, or osteocyte activity; disorders due to altered bone matrix proteins; disorders due to altered bone microenvironmental regulators; and disorders due to deranged calciotropic hormonal activity. This article provides the first comprehensive taxonomy of rare metabolic skeletal diseases based on deranged metabolic activity. This classification will help in the development of common and shared diagnostic and therapeutic pathways for these patients and also in the creation of international registries of rare skeletal diseases, the first step for the development of genetic tests based on next generation sequencing and for performing large intervention trials to assess efficacy of orphan drugs.

  17. Calcium homeostasis and vitamin D metabolism and expression in strongly calcifying laying birds.

    PubMed

    Bar, Arie

    2008-12-01

    Egg laying and shell calcification impose severe extra demands on ionic calcium (Ca2+) homeostasis; especially in birds characterized by their long clutches (series of eggs laid sequentially before a "pause day"). These demands induce vitamin D metabolism and expression. The metabolism of vitamin D is also altered indirectly, by other processes associated with increased demands for calcium, such as growth, bone formation and egg production. A series of intestinal, renal or bone proteins are consequently expressed in the target organs via mechanisms involving a vitamin D receptor. Some of these proteins (carbonic anhydrase, calbindin and calcium-ATPase) are also found in the uterus (eggshell gland) or are believed to be involved in calcium transport in the intestine or kidney (calcium channels). The present review deals with vitamin D metabolism and the expression of the above-mentioned proteins in birds, with special attention to the strongly calcifying laying bird.

  18. Endothelial dysfunction in metabolic and vascular disorders.

    PubMed

    Polovina, Marija M; Potpara, Tatjana S

    2014-03-01

    Vascular endothelium has important regulatory functions in the cardiovascular system and a pivotal role in the maintenance of vascular health and metabolic homeostasis. It has long been recognized that endothelial dysfunction participates in the pathogenesis of atherosclerosis from early, preclinical lesions to advanced, thrombotic complications. In addition, endothelial dysfunction has been recently implicated in the development of insulin resistance and type 2 diabetes mellitus (T2DM). Considering that states of insulin resistance (eg, metabolic syndrome, impaired fasting glucose, impaired glucose tolerance, and T2DM) represent the most prevalent metabolic disorders and risk factors for atherosclerosis, it is of considerable scientific and clinical interest that both metabolic and vascular disorders have endothelial dysfunction as a common background. Importantly, endothelial dysfunction has been associated with adverse outcomes in patients with established cardiovascular disease, and a growing body of evidence indicates that endothelial dysfunction also imparts adverse prognosis in states of insulin resistance. In this review, we discuss the association of insulin resistance and T2DM with endothelial dysfunction and vascular disease, with a focus on the underlying mechanisms and prognostic implications of the endothelial dysfunction in metabolic and vascular disorders. We also address current therapeutic strategies for the improvement of endothelial dysfunction.

  19. Calcium Co-regulates Oxidative Metabolism and ATP Synthase-dependent Respiration in Pancreatic Beta Cells

    PubMed Central

    De Marchi, Umberto; Thevenet, Jonathan; Hermant, Aurelie; Dioum, Elhadji; Wiederkehr, Andreas

    2014-01-01

    Mitochondrial energy metabolism is essential for glucose-induced calcium signaling and, therefore, insulin granule exocytosis in pancreatic beta cells. Calcium signals are sensed by mitochondria acting in concert with mitochondrial substrates for the full activation of the organelle. Here we have studied glucose-induced calcium signaling and energy metabolism in INS-1E insulinoma cells and human islet beta cells. In insulin secreting cells a surprisingly large fraction of total respiration under resting conditions is ATP synthase-independent. We observe that ATP synthase-dependent respiration is markedly increased after glucose stimulation. Glucose also causes a very rapid elevation of oxidative metabolism as was followed by NAD(P)H autofluorescence. However, neither the rate of the glucose-induced increase nor the new steady-state NAD(P)H levels are significantly affected by calcium. Our findings challenge the current view, which has focused mainly on calcium-sensitive dehydrogenases as the target for the activation of mitochondrial energy metabolism. We propose a model of tight calcium-dependent regulation of oxidative metabolism and ATP synthase-dependent respiration in beta cell mitochondria. Coordinated activation of matrix dehydrogenases and respiratory chain activity by calcium allows the respiratory rate to change severalfold with only small or no alterations of the NAD(P)H/NAD(P)+ ratio. PMID:24554722

  20. Interactions between calcium precipitation and the polyphosphate-accumulating bacteria metabolism.

    PubMed

    Barat, R; Montoya, T; Borrás, L; Ferrer, J; Seco, A

    2008-07-01

    A sequencing batch reactor that is operated for biological phosphorus removal has been operated under different influent calcium concentrations to study the precipitation process and the possible effects of phosphorus precipitation in the biological phosphorus removal process. Four experiments were carried out under different influent calcium concentrations ranging from 10 to 90 g Ca m(-3). The experimental results and the equilibrium study, which are based on the saturation index calculation, confirm that the process controlling the calcium behaviour is the calcium phosphate precipitation. This precipitation takes place at two stages: initially, precipitation of the amorphous calcium phosphate, and later crystallization of hydroxyapatite. Also the accumulation of phosphorus precipitated was observed when the influent calcium concentration was increased. In all the experiments, the influent wastewater ratio P/COD was kept constant. It has been observed that, at high calcium concentration, the ratio between phosphate release and acetate uptake (P(rel)/Ac(uptake)) decreases. Changes in the polyphosphate-accumulating organism (PAO) population and in the glycogen-accumulating organism (GAO) population during the experimental period were ruled out by means of fluorescence in situ hybridization. These results could suggest that PAO are able to change their metabolic pathways based on external conditions, such as influent calcium concentration. The accumulation of phosphorus precipitated as calcium phosphate at high influent calcium concentration throughout the experimental period confirmed that phosphate precipitation is a process that can affect the PAO metabolism.

  1. Bone Markers, Calcium Metabolism, and Calcium Kinetics During Extended-Duration Space Flight on the Mir Space Station

    NASA Technical Reports Server (NTRS)

    Smith, Scott M.; Wastney, Meryl E.; O'Brien, Kimberly O.; Morukov, Boris V.; Larina, Irina M.; Abrams, Steven A.; Davis-Street, Janis E.; Oganov, Victor; Shackelford, Linda C.

    2005-01-01

    Bone loss is a current limitation for long-term space exploration. Bone markers, calcitropic hormones, and calcium kinetics of crew members on space missions of 4-6 months were evaluated. Spaceflight-induced bone loss was associated with increased bone resorption and decreased calcium absorption. INTRODUCTION: Bone loss is a significant concern for the health of astronauts on long-duration missions. Defining the time course and mechanism of these changes will aid in developing means to counteract these losses during space flight and will have relevance for other clinical situations that impair weight-bearing activity. MATERIALS AND METHODS: We report here results from two studies conducted during the Shuttle-Mir Science Program. Study 1 was an evaluation of bone and calcium biochemical markers of 13 subjects before and after long-duration (4-6 months) space missions. In study 2, stable calcium isotopes were used to evaluate calcium metabolism in six subjects before, during, and after flight. Relationships between measures of bone turnover, biochemical markers, and calcium kinetics were examined. RESULTS: Pre- and postflight study results confirmed that, after landing, bone resorption was increased, as indicated by increases in urinary calcium (p < 0.05) and collagen cross-links (N-telopeptide, pyridinoline, and deoxypyridinoline were all increased >55% above preflight levels, p < 0.001). Parathyroid hormone and vitamin D metabolites were unchanged at landing. Biochemical markers of bone formation were unchanged at landing, but 2-3 weeks later, both bone-specific alkaline phosphatase and osteocalcin were significantly (p < 0.01) increased above preflight levels. In studies conducted during flight, bone resorption markers were also significantly higher than before flight. The calcium kinetic data also validated that bone resorption was increased during flight compared with preflight values (668 +/- 130 versus 427 +/- 153 mg/day; p < 0.001) and clearly documented that

  2. Crosstalk between metabolic and neuropsychiatric disorders.

    PubMed

    Kaidanovich-Beilin, Oksana; Cha, Danielle S; McIntyre, Roger S

    2012-01-01

    Evidence supporting the concurrence of metabolic disturbances (e.g. insulin resistance, diabetes and obesity) and neuropsychiatric disorders has been demonstrated in both human and animal studies, suggesting the possibility that they have shared pathophysiological mechanisms. During the past decade, our understanding for the role of insulin in both normal and abnormal central nervous system (CNS) processes has become increasingly refined. Evidence indicates that insulin is a pleiotropic peptide, critical to neurotrophism, neuroplasticity, and neuromodulation. Moreover, the role of insulin underscores its importance in the development of several neuropsychiatric disorders, including, but not limited to, mechanisms involved in the pathogenesis and progression towards diabetes, obesity, and neurodegenerative disorders, such as Alzheimer's disease. This review focuses on the insulin-mediated effects on normal and abnormal brain function and discusses why targeting insulin-related pathways in the brain may emerge as a new approach for refining treatment of neurological and psychiatric disorders.

  3. Crosstalk between metabolic and neuropsychiatric disorders

    PubMed Central

    Cha, Danielle S.

    2012-01-01

    Evidence supporting the concurrence of metabolic disturbances (e.g. insulin resistance, diabetes and obesity) and neuropsychiatric disorders has been demonstrated in both human and animal studies, suggesting the possibility that they have shared pathophysiological mechanisms. During the past decade, our understanding for the role of insulin in both normal and abnormal central nervous system (CNS) processes has become increasingly refined. Evidence indicates that insulin is a pleiotropic peptide, critical to neurotrophism, neuroplasticity, and neuromodulation. Moreover, the role of insulin underscores its importance in the development of several neuropsychiatric disorders, including, but not limited to, mechanisms involved in the pathogenesis and progression towards diabetes, obesity, and neurodegenerative disorders, such as Alzheimer's disease. This review focuses on the insulin-mediated effects on normal and abnormal brain function and discusses why targeting insulin-related pathways in the brain may emerge as a new approach for refining treatment of neurological and psychiatric disorders. PMID:22802875

  4. Confocal microscope is able to detect calcium metabolic in neuronal infection by toxoplasma gondii

    NASA Astrophysics Data System (ADS)

    Sensusiati, A. D.; Priya, T. K. S.; Dachlan, Y. P.

    2017-05-01

    Calcium metabolism plays a very important role in neurons infected by Toxoplasma. Detection of change of calcium metabolism of neuron infected by Toxoplasma and Toxoplasma requires the calculation both quantitative and qualitative method. Confocal microscope has the ability to capture the wave of the fluorescent emission of the fluorescent dyes used in the measurement of cell calcium. The purpose of this study was to prove the difference in calcium changes between infected and uninfected neurons using confocal microscopy. Neuronal culture of human-skin-derived neural stem cell were divided into 6 groups, consisting 3 uninfected groups and 3 infected groups. Among the 3 groups were 2 hours, 24 hours and 48 hours. The neuron Toxoplasma gondii ratio was 1:5. Observation of intracellular calcium of neuron and tachyzoite, evidence of necrosis, apoptosis and the expression of Hsp 70 of neuron were examined by confocal microscope. The normality of the data was analysed by Kolmogorov-Smirnov Test, differentiation test was checked by t2 Test, and ANOVAs, for correlation test was done by Pearson Correlation Test. The calcium intensity of cytosolic neuron and T. gondii was significantly different from control groups (p<0.05). There was also significant correlation between calcium intensity with the evidence of necrosis and Hsp70 expression at 2 hours after infection. Apoptosis and necrosis were simultaneously shown with calcium contribution in this study. Confocal microscopy can be used to measure calcium changes in infected and uninfected neurons both in quantitatively and qualitatively.

  5. Metabolic and toxic causes of canine seizure disorders: A retrospective study of 96 cases.

    PubMed

    Brauer, Christina; Jambroszyk, Melanie; Tipold, Andrea

    2011-02-01

    A wide variety of intoxications and abnormal metabolic conditions can lead to reactive seizures in dogs. Patient records of dogs suffering from seizure disorders (n=877) were reviewed, and 96 cases were associated with an underlying metabolic or toxic aetiology. These included intoxications by various agents, hypoglycaemia, electrolyte disorders, hepatic encephalopathy, hypothyroidism, uraemic encephalopathy, hypoxia and hyperglycaemia. The incidence of the underlying diseases was determined. The most common causes of reactive seizures were intoxications (39%, 37 dogs) and hypoglycaemia (32%, 31 dogs). Hypocalcaemia was the most frequent electrolyte disorder causing reactive seizures (5%) and all five of these dogs had ionised calcium concentrations ≤0.69 mmol/L. Eleven per cent of dogs with seizures had metabolic or toxic disorders and this relatively high frequency emphasises the importance of a careful clinical work-up of cases presented with seizures in order to reach a correct diagnosis and select appropriate treatment options. Copyright © 2009 Elsevier Ltd. All rights reserved.

  6. Derangement of calcium metabolism in diabetes mellitus: negative outcome from the synergy between impaired bone turnover and intestinal calcium absorption.

    PubMed

    Wongdee, Kannikar; Krishnamra, Nateetip; Charoenphandhu, Narattaphol

    2017-01-01

    Both types 1 and 2 diabetes mellitus (T1DM and T2DM) are associated with profound deterioration of calcium and bone metabolism, partly from impaired intestinal calcium absorption, leading to a reduction in calcium uptake into the body. T1DM is associated with low bone mineral density (BMD) and osteoporosis, whereas the skeletal changes in T2DM are variable, ranging from normal to increased and to decreased BMD. However, both types of DM eventually compromise bone quality through production of advanced glycation end products and misalignment of collagen fibrils (so-called matrix failure), thereby culminating in a reduction of bone strength. The underlying cellular mechanisms (cellular failure) are related to suppression of osteoblast-induced bone formation and bone calcium accretion, as well as to enhancement of osteoclast-induced bone resorption. Several other T2DM-related pathophysiological changes, e.g., osteoblast insulin resistance, impaired productions of osteogenic growth factors (particularly insulin-like growth factor 1 and bone morphogenetic proteins), overproduction of pro-inflammatory cytokines, hyperglycemia, and dyslipidemia, also aggravate diabetic osteopathy. In the kidney, DM and the resultant hyperglycemia lead to calciuresis and hypercalciuria in both humans and rodents. Furthermore, DM causes deranged functions of endocrine factors related to mineral metabolism, e.g., parathyroid hormone, 1,25-dihydroxyvitamin D 3 , and fibroblast growth factor-23. Despite the wealth of information regarding impaired bone remodeling in DM, the long-lasting effects of DM on calcium metabolism in young growing individuals, pregnant women, and neonates born to women with gestational DM have received scant attention, and their underlying mechanisms are almost unknown and worth exploring.

  7. [Strontium and calcium metabolism. Interaction of strontium and vitamin D].

    PubMed

    Rousselet, F; El Solh, N; Maurat, J P; Gruson, M; Girard, M L

    1975-01-01

    Oral administration of strontium to calcium wellfed rats blocks the intestinal absorption of calcium. When high doses of vitamine D are given over long period, the inhibition of calcium intestinal absorption disapears. Under these conditions the absorption of strontium is increased. It is suggested that there is only one absorption mechanism for these two cations. An overdose of the vitamine D increases the renal elimination of strontium but under these conditions the plasma concentration of the strontium is unchanged. Vitamine D brings about the some action on the bone fixation of the strontium as it does on the bone fixation of calcium. The bone fixation is increased with low dosages. The bone fixation is decreased with high dosages.

  8. [Inherited metabolic disorders in pediatric emergency services].

    PubMed

    Molina Gutiérrez, M A; López López, R; Morais López, A; Bueno Barriocanal, M; Martínez Ojinaga Nodal, E; Alcolea Sánchez, A M; García García, S

    2015-06-01

    Advances in the early diagnosis and treatment have led to improved survival, and a better quality of life for patients with inherited metabolic disorders (IMD). They can go to the Pediatric Emergency Services (PES) for reasons unrelated to their disease. The purpose of this study was to review the characteristics of visitors to the PES of these patients in a tertiary hospital. A retrospective observational study was conducted on all visits from patients with IMD to the PES of Hospital Infantil La Paz over the years 2011 and 2012. IMD type, complaint, duration of symptoms, need for hospitalization, and presence of metabolic decompensation was recorded. A total of 107 visits were analyzed, with the most frequent reason being for consultation of respiratory processes (30.8%). When the consultation was for vomiting, patients with protein-related disorders were those who delayed less in going to PES. One third of visitors were admitted, half of them due to metabolic decompensation of the underlying pathology. Patients with IMD came to PES for many different reasons, which in some cases were the cause or consequence of an acute metabolic decompensation that led to hospitalization. Being diseases with low prevalence, it would be useful to have diagnostic and therapeutic protocols in order to provide optimal care. Copyright © 2014 Asociación Española de Pediatría. Published by Elsevier España, S.L.U. All rights reserved.

  9. Calcium

    MedlinePlus

    ... You'll also find calcium in broccoli and dark green, leafy vegetables (especially collard and turnip greens, ... can enjoy good sources of calcium such as dark green, leafy vegetables, broccoli, chickpeas, and calcium-fortified ...

  10. Neuronal Calcium Signaling in Metabolic Regulation and Adaptation to Nutrient Stress.

    PubMed

    Jayakumar, Siddharth; Hasan, Gaiti

    2018-01-01

    All organisms can respond physiologically and behaviorally to environmental fluxes in nutrient levels. Different nutrient sensing pathways exist for specific metabolites, and their inputs ultimately define appropriate nutrient uptake and metabolic homeostasis. Nutrient sensing mechanisms at the cellular level require pathways such as insulin and target of rapamycin (TOR) signaling that integrates information from different organ systems like the fat body and the gut. Such integration is essential for coordinating growth with development. Here we review the role of a newly identified set of integrative interneurons and the role of intracellular calcium signaling within these neurons, in regulating nutrient sensing under conditions of nutrient stress. A comparison of the identified Drosophila circuit and cellular mechanisms employed in this circuit, with vertebrate systems, suggests that the identified cell signaling mechanisms may be conserved for neural circuit function related to nutrient sensing by central neurons. The ideas proposed are potentially relevant for understanding the molecular basis of metabolic disorders, because these are frequently linked to nutritional stress.

  11. Calcium metabolism before, during, and after a 3-mo spaceflight: kinetic and biochemical changes

    NASA Technical Reports Server (NTRS)

    Smith, S. M.; Wastney, M. E.; Morukov, B. V.; Larina, I. M.; Nyquist, L. E.; Abrams, S. A.; Taran, E. N.; Shih, C. Y.; Nillen, J. L.; Davis-Street, J. E.; hide

    1999-01-01

    The loss of bone during spaceflight is considered a physiological obstacle for the exploration of other planets. This report of calcium metabolism before, during, and after long-duration spaceflight extends results from Skylab missions in the 1970s. Biochemical and endocrine indexes of calcium and bone metabolism were measured together with calcium absorption, excretion, and bone turnover using stable isotopes. Studies were conducted before, during, and after flight in three male subjects. Subjects varied in physical activity, yet all lost weight during flight. During flight, calcium intake and absorption decreased up to 50%, urinary calcium excretion increased up to 50%, and bone resorption (determined by kinetics or bone markers) increased by over 50%. Osteocalcin and bone-specific alkaline phosphatase, markers of bone formation, increased after flight. Subjects lost approximately 250 mg bone calcium per day during flight and regained bone calcium at a slower rate of approximately 100 mg/day for up to 3 mo after landing. Further studies are required to determine the time course of changes in calcium homeostasis during flight to develop and assess countermeasures against flight-induced bone loss.

  12. Metabolic Consequences of Sleep-Disordered Breathing

    PubMed Central

    Jun, Jonathan; Polotsky, Vsevolod Y.

    2017-01-01

    There is increasing evidence of a causal relationship between sleep-disordered breathing and metabolic dysfunction. Metabolic syndrome (MetS), a cluster of risk factors that promote atherosclerotic cardiovascular disease, comprises central obesity, insulin resistance, glucose intolerance, dyslipidemia, and hypertension, manifestations of altered total body energy regulation. Excess caloric intake is indisputably the key driver of MetS, but other environmental and genetic factors likely play a role; in particular, obstructive sleep apnea (OSA), characterized by intermittent hypoxia (IH), may induce or exacerbate various aspects of MetS. Clinical studies show that OSA can affect glucose metabolism, cholesterol, inflammatory markers, and nonalcoholic fatty liver disease. Animal models of OSA enable scientists to circumvent confounders such as obesity in clinical studies. In the most widely used model, which involves exposing rodents to IH during their sleep phase, the IH alters circadian glucose homeostasis, impairs muscle carbohydrate uptake, induces hyperlipidemia, and upregulates cholesterol synthesis enzymes. Complicating factors such as obesity or a high-fat diet lead to progressive insulin resistance and liver inflammation, respectively. Mechanisms for these effects are not yet fully understood, but are likely related to energy-conserving adaptations to hypoxia, which is a strong catabolic stressor. Finally, IH may contribute to the morbidity of MetS by inducing inflammation and oxidative stress. Identification of OSA as a potential causative factor in MetS would have immense clinical impact and could improve the management and understanding of both disorders. PMID:19506316

  13. Dietary Sodium Effects on Bone Loss and Calcium Metabolism During Bed Rest

    NASA Technical Reports Server (NTRS)

    Smith, Scott M.; Arnaud, Sara B.; Abrams, Steven A.; Paloski, W. H. (Technical Monitor)

    2000-01-01

    The acceleration of age-related bone loss is one of the most detrimental effects of space flight. The ability to understand and counteract this loss will be critical for crew health and safety during and after long-duration missions. Studies in healthy ambulatory individuals have linked high salt (sodium) diets, hypercalciuria, and increased renal stone risk. Dietary salt may modulate bone loss through changes in calcium metabolism and the calcium endocrine system. The research proposed here will determine the role of dietary salt in the loss of bone during simulated space flight. Calcium metabolism will be determined through calcium kinetics studies, endocrine and biochemical measurements; and estimates of the mass, distribution and mechanical properties of bone, in subjects fed low (100 mmol sodium/day) or high (250 mmol sodium/day) levels of dietary salt during 28 days of headdown tilt bedrest. This research addresses the role of dietary salt in the loss of bone and calcium in space flight, and integrates the changes in calcium metabolism with those occurring in other physiologic systems. These data will be critical for both countermeasure development, and in determination of nutritional requirements for extended-duration space flight. The potential countermeasures resulting from this research will reduce health risks due to acceleration of age-related osteoporosis and increased risk of renal stone formation..

  14. [The functions of calcium-sensing receptor in regulating mineral metabolism.

    PubMed

    Kinoshita, Yuka

    Calcium-sensing receptor(CaSR)which belongs to a G protein-coupled receptor family is one of the key elements in regulating calcium homeostasis. CaSR has been identified as a receptor to control parathyroid hormone(PTH)secretion in parathyroid glands according to serum calcium ion(Ca2+)levels. It has also been shown that CaSR controls reabsorption of water and several cations including Ca2+and magnesium ion(Mg2+)in renal tubular cells. This review summarizes the functions and roles of CaSR in mineral metabolism that are exerted in parathyroid glands, kidney, and intestine.

  15. Pulmonary complications of endocrine and metabolic disorders.

    PubMed

    Milla, Carlos E; Zirbes, Jacquelyn

    2012-03-01

    There are many important respiratory manifestations of endocrine and metabolic diseases in children. Acute and chronic pulmonary infections are the most common respiratory abnormalities in patients with diabetes mellitus, although cardiogenic and non-cardiogenic pulmonary oedema are also possible. Pseudohypoaldosteronism type 1 may be indistinguishable from cystic fibrosis (CF) unless serum aldosterone, plasma renin activity, and urinary electrolytes are measured and mutation analysis rules out CF. Hypo- and hyperthyroidism may alter lung function and affect the central respiratory drive. The thyroid hormone plays an essential role in lung development, surfactant synthesis, and lung defence. Complications of hypoparathyroidism are largely due to hypocalcaemia. Laryngospasm can lead to stridor and airway obstruction. Ovarian tumours, benign or malignant, may present with unilateral or bilateral pleural effusions. Metabolic storage disorders, primarily as a consequence of lysosomal dysfunction from enzymatic deficiencies, constitute a diverse group of rare conditions that can have profound effects on the respiratory system. Copyright © 2011 Elsevier Ltd. All rights reserved.

  16. Zoledronic acid in pediatric metabolic bone disorders.

    PubMed

    Bowden, Sasigarn A; Mahan, John D

    2017-10-01

    Zoledronic acid (ZA), a highly potent intravenous bisphosphonate (BP), has been increasingly used in children with primary and secondary osteoporosis due to its convenience of shorter infusion time and less frequent dosing compared to pamidronate. Many studies have also demonstrated beneficial effects of ZA in other conditions such as hypercalcemia of malignancy, fibrous dysplasia (FD), chemotherapy-related osteonecrosis (ON) and metastatic bone disease. This review summarizes pharmacologic properties, mechanism of action, dosing regimen, and therapeutic outcomes of ZA in a variety of metabolic bone disorders in children. Several potential novel uses of ZA are also discussed. Safety concerns and adverse effects are also highlighted.

  17. Zoledronic acid in pediatric metabolic bone disorders

    PubMed Central

    Mahan, John D.

    2017-01-01

    Zoledronic acid (ZA), a highly potent intravenous bisphosphonate (BP), has been increasingly used in children with primary and secondary osteoporosis due to its convenience of shorter infusion time and less frequent dosing compared to pamidronate. Many studies have also demonstrated beneficial effects of ZA in other conditions such as hypercalcemia of malignancy, fibrous dysplasia (FD), chemotherapy-related osteonecrosis (ON) and metastatic bone disease. This review summarizes pharmacologic properties, mechanism of action, dosing regimen, and therapeutic outcomes of ZA in a variety of metabolic bone disorders in children. Several potential novel uses of ZA are also discussed. Safety concerns and adverse effects are also highlighted. PMID:29184807

  18. Uric Acid Nephrolithiasis: A Systemic Metabolic Disorder

    PubMed Central

    Moe, Orson W.

    2014-01-01

    Uric acid nephrolithiasis is characteristically a manifestation of a systemic metabolic disorder. It has a prevalence of about 10% among all stone formers, the third most common type of kidney stone in the industrialized world. Uric acid stones form primarily due to an unduly acid urine; less deciding factors are hyperuricosuria and a low urine volume. The vast majority of uric acid stone formers have the metabolic syndrome, and not infrequently, clinical gout is present as well. A universal finding is a low baseline urine pH plus insufficient production of urinary ammonium buffer. Persons with gastrointestinal disorders, in particular chronic diarrhea or ostomies, and patients with malignancies with a large tumor mass and high cell turnover comprise a less common but nevertheless important subset. Pure uric acid stones are radiolucent but well visualized on renal ultrasound. A 24 h urine collection for stone risk analysis provides essential insight into the pathophysiology of stone formation and may guide therapy. Management includes a liberal fluid intake and dietary modification. Potassium citrate to alkalinize the urine to a goal pH between 6 and 6.5 is essential, as undissociated uric acid deprotonates into its much more soluble urate form. PMID:25045326

  19. Effect of calcium phosphate and vitamin D₃ supplementation on bone remodelling and metabolism of calcium, phosphorus, magnesium and iron.

    PubMed

    Trautvetter, Ulrike; Neef, Nadja; Leiterer, Matthias; Kiehntopf, Michael; Kratzsch, Jürgen; Jahreis, Gerhard

    2014-01-17

    The aim of the present study was to determine the effect of calcium phosphate and/or vitamin D₃ on bone and mineral metabolism. Sixty omnivorous healthy subjects participated in the double-blind, placebo-controlled parallel designed study. Supplements were tricalcium phosphate (CaP) and cholecalciferol (vitamin D₃). At the beginning of the study (baseline), all subjects documented their normal nutritional habits in a dietary record for three successive days. After baseline, subjects were allocated to three intervention groups: CaP (additional 1 g calcium/d), vitamin D₃ (additional 10 μg/d) and CaP + vitamin D₃. In the first two weeks, all groups consumed placebo bread, and afterwards, for eight weeks, the test bread according to the intervention group. In the last week of each study period (baseline, placebo, after four and eight weeks of intervention), a faecal (three days) and a urine (24 h) collection and a fasting blood sampling took place. Calcium, phosphorus, magnesium and iron were determined in faeces, urine and blood. Bone formation and resorption markers were analysed in blood and urine. After four and eight weeks, CaP and CaP + vitamin D₃ supplementations increased faecal excretion of calcium and phosphorus significantly compared to placebo. Due to the vitamin D₃ supplementations (vitamin D₃, CaP + vitamin D₃), the plasma 25-(OH)D concentration significantly increased after eight weeks compared to placebo. The additional application of CaP led to a significant increase of the 25-(OH)D concentration already after four weeks. Bone resorption and bone formation markers were not influenced by any intervention. Supplementation with daily 10 μg vitamin D₃ significantly increases plasma 25-(OH)D concentration. The combination with daily 1 g calcium (as CaP) has a further increasing effect on the 25-(OH)D concentration. Both CaP alone and in combination with vitamin D₃ have no beneficial effect on bone remodelling markers and on

  20. Calcium

    MedlinePlus

    ... Guidelines for Americans and the U.S. Department of Agriculture's MyPlate . Where can I find out more about ... on food sources of calcium: U.S. Department of Agriculture's (USDA) National Nutrient Database Nutrient List for calcium ( ...

  1. A brief review of space flight calcium metabolism: Results and methodologies

    NASA Technical Reports Server (NTRS)

    1978-01-01

    Space flight induced osteoporosis was described. The techniques that were used to measure and detect the osteoporosis were also described. Areas of calcium metabolism were shown to be very important in the investigation into more sensitive detection and measurement techniques of bone demineralization.

  2. Devastating metabolic brain disorders of newborns and young infants.

    PubMed

    Yoon, Hyun Jung; Kim, Ji Hye; Jeon, Tae Yeon; Yoo, So-Young; Eo, Hong

    2014-01-01

    Metabolic disorders of the brain that manifest in the neonatal or early infantile period are usually associated with acute and severe illness and are thus referred to as devastating metabolic disorders. Most of these disorders may be classified as organic acid disorders, amino acid metabolism disorders, primary lactic acidosis, or fatty acid oxidation disorders. Each disorder has distinctive clinical, biochemical, and radiologic features. Early diagnosis is important both for prompt treatment to prevent death or serious sequelae and for genetic counseling. However, diagnosis is often challenging because many findings overlap and may mimic those of more common neonatal conditions, such as hypoxic-ischemic encephalopathy and infection. Ultrasonography (US) may be an initial screening method for the neonatal brain, and magnetic resonance (MR) imaging is the modality of choice for evaluating metabolic brain disorders. Although nonspecific imaging findings are common in early-onset metabolic disorders, characteristic patterns of brain involvement have been described for several disorders. In addition, diffusion-weighted images may be used to characterize edema during an acute episode of encephalopathy, and MR spectroscopy depicts changes in metabolites that may help diagnose metabolic disorders and assess response to treatment. Imaging findings, including those of advanced MR imaging techniques, must be closely reviewed. If one of these rare disorders is suspected, the appropriate biochemical test or analysis of the specific gene should be performed to confirm the diagnosis. ©RSNA, 2014.

  3. Dietary protein, calcium metabolism and bone health in humans

    USDA-ARS?s Scientific Manuscript database

    Protein is the major structural constituent of bone (50% by volume). But it is also a major source of metabolic acid, especially protein from animal sources because it contains sulfur amino acids that generate sulfuric acid. Increased potential renal acid load has been closely associated with increa...

  4. Genetic variants of ghrelin in metabolic disorders.

    PubMed

    Ukkola, Olavi

    2011-11-01

    An increasing understanding of the role of genes in the development of obesity may reveal genetic variants that, in combination with conventional risk factors, may help to predict an individual's risk for developing metabolic disorders. Accumulating evidence indicates that ghrelin plays a role in regulating food intake and energy homeostasis and it is a reasonable candidate gene for obesity-related co-morbidities. In cross-sectional studies low total ghrelin concentrations and some genetic polymorphisms of ghrelin have been associated with obesity-associated diseases. The present review highlights many of the important problems in association studies of genetic variants and complex diseases. It is known that population-specific differences in reported associations exist. We therefore conclude that more studies on variants of ghrelin gene are needed to perform in different populations to get deeper understanding on the relationship of ghrelin gene and its variants to obesity. Copyright © 2011 Elsevier Inc. All rights reserved.

  5. Cardiac basal metabolism: energetic cost of calcium withdrawal in the adult rat heart.

    PubMed

    Bonazzola, P; Takara, D

    2010-07-01

    Cardiac basal metabolism upon extracellular calcium removal and its relationship with intracellular sodium and calcium homeostasis was evaluated. A mechano-calorimetric technique was used that allowed the simultaneous and continuous measurement of both heat rate and resting pressure in arterially perfused quiescent adult rat hearts. Using pharmacological tools, the possible underlying mechanisms related to sodium and calcium movements were investigated. Resting heat rate (expressed in mW g(-1)(dry wt)) increased upon calcium withdrawal (+4.4 +/- 0.2). This response was: (1) unaffected by the presence of tetrodotoxin (+4.3 +/- 0.6), (2) fully blocked by both, the decrease in extracellular sodium concentration and the increase in extracellular magnesium concentration, (3) partially blocked by the presence of either nifedipine (+2.8 +/- 0.4), KB-R7943 (KBR; +2.5 +/- 0.2), clonazepam (CLO; +3.1 +/- 0.3) or EGTA (+1.9 +/- 0.3). The steady heat rate under Ca(2+)-free conditions was partially reduced by the addition of Ru360 (-1.1 +/- 0.2) but not CLO in the presence of EGTA, KBR or Ru360. Energy expenditure for resting state maintenance upon calcium withdrawal depends on the intracellular rise in both sodium and calcium. Our data are consistent with a mitochondrial Ca(2+) cycling, not detectable under normal calcium diastolic levels. The experimental condition here analysed, partially simulates findings reported under certain pathological situations including heart failure in which mildly increased levels of both diastolic sodium and calcium have also been found. Therefore, under such pathological conditions, hearts should distract chemical energy to fuel processes associated with sodium and calcium handling, making more expensive the maintenance of their functions.

  6. - Invited Review - Calcium Digestibility and Metabolism in Pigs*

    PubMed Central

    González-Vega, J. C.; Stein, H. H.

    2014-01-01

    Calcium (Ca) and phosphorus (P) are minerals that have important physiological functions in the body. For formulation of diets for pigs, it is necessary to consider an appropriate Ca:P ratio for an adequate absorption and utilization of both minerals. Although both minerals are important, much more research has been conducted on P digestibility than on Ca digestibility. Therefore, this review focuses on aspects that are important for the digestibility of Ca. Only values for apparent total tract digestibility (ATTD) of Ca have been reported in pigs, whereas values for both ATTD and standardized total tract digestibility (STTD) of P in feed ingredients have been reported. To be able to determine STTD values for Ca it is necessary to determine basal endogenous losses of Ca. Although most Ca is absorbed in the small intestine, there are indications that Ca may also be absorbed in the colon under some circumstances, but more research to verify the extent of Ca absorption in different parts of the intestinal tract is needed. Most P in plant ingredients is usually bound to phytate. Therefore, plant ingredients have low digestibility of P due to a lack of phytase secretion by pigs. During the last 2 decades, inclusion of microbial phytase in swine diets has improved P digestibility. However, it has been reported that a high inclusion of Ca reduces the efficacy of microbial phytase. It is possible that formation of insoluble calcium-phytate complexes, or Ca-P complexes, not only may affect the efficacy of phytase, but also the digestibility of P and Ca. Therefore, Ca, P, phytate, and phytase interactions are aspects that need to be considered in Ca digestibility studies. PMID:25049919

  7. Quantitation of calcium metabolism in postmenopausal osteoporosis and in scoliosis

    SciTech Connect

    Bronner, F.; Richelle, L. J.; Saville, P. D.

    1963-06-01

    By a combination of balance and isotope techniques, the following parameters of Ca metabolism were measured: pool size, rate of loss from pool, urinary excretion, fecal excretion, intake, endogenous fecal Ca, absorption, balance, bone formation, and bone resorption. The subjects were two normal women and five women with postmenopausal osteoporosis, aged 41 to 74 years, and four patients with scoliosis, aged 12 to 22 years. The latter were studied before, shortly after, and many months after immobilization in plaster casts. On the basis of observed relationships, it appeared that the negative Ca balance observed in the older women was duemore » to the low intensity of the various vectors of Ca metabolism, without clearcut distinction between the subjects with and without osteoporosis. Conversely, in the young patients with scoliosis, the negative balance incident to treatment by immobilization was associated with vectors of relatively high intensity whose relationships were altered temporarily.« less

  8. Increasing serotonin concentrations alter calcium and energy metabolism in dairy cows.

    PubMed

    Laporta, Jimena; Moore, Spencer A E; Weaver, Samantha R; Cronick, Callyssa M; Olsen, Megan; Prichard, Austin P; Schnell, Brian P; Crenshaw, Thomas D; Peñagaricano, Francisco; Bruckmaier, Rupert M; Hernandez, Laura L

    2015-07-01

    A 4×4 Latin square design in which varied doses (0, 0.5, 1.0, and 1.5 mg/kg) of 5-hydroxy-l-tryptophan (5-HTP, a serotonin precursor) were intravenously infused into late-lactation, non-pregnant Holstein dairy cows was used to determine the effects of serotonin on calcium and energy metabolism. Infusion periods lasted 4 days, with a 5-day washout between periods. Cows were infused at a constant rate for 1 h each day. Blood was collected pre- and 5, 10, 30, 60, 90, and 120 min post-infusion, urine was collected pre- and post-infusion, and milk was collected daily. All of the 5-HTP doses increased systemic serotonin as compared to the 0 mg/kg dose, and the 1.0 and 1.5 mg/kg doses increased circulating glucose and non-esterified fatty acids (NEFA) and decreased beta-hydroxybutyrate (βHBA) concentrations. Treatment of cows with either 1.0 or 1.5 mg/kg 5-HTP doses decreased urine calcium elimination, and the 1.5 mg/kg dose increased milk calcium concentrations. No differences were detected in the heart rates, respiration rates, or body temperatures of the cows; however, manure scores and defecation frequency were affected. Indeed, cows that received 5-HTP defecated more, and the consistency of their manure was softer. Treatment of late-lactation dairy cows with 5-HTP improved energy metabolism, decreased loss of calcium into urine, and increased calcium secretion into milk. Further research should target the effects of increasing serotonin during the transition period to determine any benefits for post-parturient calcium and glucose metabolism. © 2015 Society for Endocrinology.

  9. Treatment strategies for acute metabolic disorders in neonates

    PubMed Central

    2011-01-01

    Acute metabolic emergencies in neonates represent a challenge to the medical and nursing staff. If not treated optimally, these disorders are associated with poor outcome. Early diagnosis, supportive therapy and specific measures addressing the derranged metabolic process are the gold standards for favorable results. This review highlights treatment strategies for Inborn Errors of Metabolism (IEM) presenting in the neonatal period. PMID:27493313

  10. Neuroendocrine and Metabolic Disorders in Bulimia Nervosa.

    PubMed

    Milano, Walter; Capasso, Anna

    2017-12-11

    Bulimia nervosa, is an eating disorder characterized by excessive influence of weight and body shape on the levels of self-esteem, with pervasive feelings of failure and inadequacy. The eating is characterized by the presence of episodes of uncontrolled eating (Binge), during which the person ingests mass wide variety of foods and the feeling of not being able to stop eating. This review focuses on the metabolic and hormonal alterations in the in bulimia nervosa. A literature search was conducted using the electronic database Medline and PubMed and with additional hand searches through the reference list obtained from the articles found. Journal were searched up to 2015. Inclusion criteria were: 1) full text available in English; 2) published in a peer-reviewed journal and using the following keywords: neurotrasmitters (AgRP, BDNF, αMSH, NP Y, endocannabinoids, adiponectin, CCK, ghrelin, GLP-1, insulin, leptin, PP, PYY), hormones (FSH, LH, estrogen, progesterone, testosterone) and bulimia nervosa, eating disorders. All data reported in the present review indicated that changes in the central and peripheral neuroendocrine equilibria may favor the onset and influence the course and prognosis of an DA. However, it is still questionable whether the alterations of the peptides and hormones regulating the mechanisms of eating behavior are the cause or consequence of a compromised diet. The results of the present review indicate that the altered balance of the various peptides or hormones can be relevant not only for the genesis and / or maintenance of altered dietary behaviors, but also for the development of specific psychopathological aspects in eating disorders. Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.org.

  11. Do sleep disorders and associated treatments impact glucose metabolism?

    PubMed

    Punjabi, Naresh M

    2009-01-01

    Over the past decade substantial evidence has accumulated implicating disorders of sleep in the pathogenesis of various metabolic abnormalities. This review, which is based on workshop discussions that took place at the 6th annual meeting of the International Sleep Disorders Forum: The Art of Good Sleep 2008 and a systematic literature search, provides a critical analysis of the available evidence implicating sleep disorders such as obstructive sleep apnoea (OSA), insomnia, short or long-term sleep duration and restless legs syndrome as potential risk factors for insulin resistance, glucose intolerance, type 2 diabetes mellitus and the metabolic syndrome. The review also highlights the evidence on whether treatment of specific sleep disorders can decrease metabolic risk. In total, 83 published reports were selected for inclusion. Although several studies show clear associations between sleep disorders and altered glucose metabolism, causal effects and the underlying pathophysiological mechanisms involved have not been fully elucidated. OSA appears to have the strongest association with insulin resistance, glucose intolerance, type 2 diabetes and the metabolic syndrome. There are, however, limited data supporting the hypothesis that effective treatment of sleep disorders, including OSA, has a favourable effect on glucose metabolism. Large randomized trials are thus required to address whether improvement of sleep quality and quantity can curtail excess metabolic risk. Research is also required to elucidate the mechanisms involved and to determine whether the effects of treatment for sleep disorders on glucose metabolism are dependent on the specific patient factors, the type of disorder and the duration of metabolic dysfunction. In conclusion, there is limited evidence on whether sleep disorders alter glucose metabolism and whether treatment can reduce the excess metabolic risk.

  12. Cytosolic Calcium Coordinates Mitochondrial Energy Metabolism with Presynaptic Activity

    PubMed Central

    Chouhan, Amit K.; Ivannikov, Maxim V.; Lu, Zhongmin; Sugimori, Mutsuyuki; Llinas, Rodolfo R.; Macleod, Gregory T.

    2012-01-01

    Most neurons fire in bursts, imposing episodic energy demands, but how these demands are coordinated with oxidative phosphorylation is still unknown. Here, using fluorescence imaging techniques on presynaptic termini of Drosophila motor neurons (MNs), we show that mitochondrial matrix pH (pHm), inner membrane potential (Δψm), and NAD(P)H levels ([NAD(P)H]m) increase within seconds of nerve stimulation. The elevations of pHm, Δψm, and [NAD(P)H]m indicate an increased capacity for ATP production. Elevations in pHm were blocked by manipulations which blocked mitochondrial Ca2+ uptake, including replacement of extracellular Ca2+ with Sr2+, and application of either tetraphenylphosphonium chloride or KB-R7943, indicating that it is Ca2+ that stimulates presynaptic mitochondrial energy metabolism. To place this phenomenon within the context of endogenous neuronal activity, the firing rates of a number of individually identified MNs were determined during fictive locomotion. Surprisingly, although endogenous firing rates are significantly different, there was little difference in presynaptic cytosolic Ca2+ levels ([Ca2+]c) between MNs when each fires at its endogenous rate. The average [Ca2+]c level (329±11nM) was slightly above the average Ca2+ affinity of the mitochondria (281±13nM). In summary, we show that when MNs fire at endogenous rates [Ca2+]c is driven into a range where mitochondria rapidly acquire Ca2+. As we also show that Ca2+ stimulates presynaptic mitochondrial energy metabolism, we conclude that [Ca2+]c levels play an integral role in coordinating mitochondrial energy metabolism with presynaptic activity in Drosophila MNs. PMID:22279208

  13. Calcium

    MedlinePlus

    ... and enzymes and to send messages through the nervous system. It is important to get plenty of calcium in the foods you eat. Foods rich in calcium include Dairy products such as milk, cheese, and yogurt Leafy, green vegetables Fish with soft bones that you eat, such as ...

  14. Calcium supplementation commencing before or early in pregnancy, or food fortification with calcium, for preventing hypertensive disorders of pregnancy.

    PubMed

    Hofmeyr, G Justus; Manyame, Sarah

    2017-09-26

    Pre-eclampsia is considerably more prevalent in low- than high-income countries. One possible explanation for this discrepancy is dietary differences, particularly calcium deficiency. Calcium supplementation in the second half of pregnancy reduces the serious consequences of pre-eclampsia and is recommended by the World Health Organization (WHO) for women with low dietary calcium intake, but has limited effect on the overall risk of pre-eclampsia. It is important to establish whether calcium supplementation before and in early pregnancy has added benefit. Such evidence would be justification for population-level fortification of staple foods with calcium. To determine the effect of calcium supplementation or food fortification with calcium, commenced before or early in pregnancy and continued at least until mid-pregnancy, on pre-eclampsia and other hypertensive disorders, maternal morbidity and mortality, as well as fetal and neonatal outcomes. We searched the Cochrane Pregnancy and Childbirth Trials Register (10 August 2017), PubMed (29 June 2017), ClinicalTrials.gov, the WHO International Clinical Trials Registry Platform (ICTRP) (10 August 2017) and reference lists of retrieved studies. Randomised controlled trials of calcium supplementation or food fortification which include women of child bearing age not yet pregnant, or in early pregnancy. Cluster-RCTs, quasi-RCTs and trials published in abstract form only would have been eligible for inclusion in this review but none were identified. Cross-over designs are not appropriate for this intervention.The scope of this review is to consider interventions including calcium supplementation with or without additional supplements or treatments, compared with placebo or no intervention. Two review authors independently assessed trials for inclusion and risk of bias, extracted data and checked them for accuracy. This review is based on one RCT (involving 60 women) which looked at calcium plus additional supplements

  15. Determinants of calcium and oxalate excretion in subjects with calcium nephrolithiasis: the role of metabolic syndrome traits.

    PubMed

    Ticinesi, Andrea; Guerra, Angela; Allegri, Franca; Nouvenne, Antonio; Cervellin, Gianfranco; Maggio, Marcello; Lauretani, Fulvio; Borghi, Loris; Meschi, Tiziana

    2018-06-01

    The association of metabolic syndrome (MetS) traits with urinary calcium (UCE) or oxalate excretion (UOE) is uncertain in calcium stone formers (CSFs). Our aim was to investigate this association in a large group of Caucasian CSFs. We retrospectively reviewed data of CSFs evaluated at our Kidney Stone Clinic from 1984 to 2015. Data on body mass index (BMI), MetS traits defined according to international consensus, family history of urolithiasis, anti-hypertensive treatments, calcemia, renal function, and 24-h urinary profile of lithogenic risk were collected. The association between MetS traits and UCE or UOE was tested with multivariate linear regression models accounting for a long list of potential confounders. We included 3003 CSFs, aged 44 ± 14 years. The prevalence of hypertension, diabetes, overweight (BMI ≥ 25 kg/m 2 ) and dyslipidemia was 17, 2, 42 and 38%, respectively. Median values of UCE and UOE were 211 mg/24 h (IQR 143-296) and 28 mg/24 h (IQR 22-34), respectively. At a multivariate model, including age, sex, date of examination, drug treatments, family history, renal function, blood calcium and urinary factors as covariates, hypertension was a significant positive determinant of UCE (β ± SE 0.23 ± 0.07, p = 0.003), but overweight, dyslipidemia and diabetes were not. No MetS trait was significantly associated with UOE in multivariate models. In a large group of Caucasian CSFs, hypertension was the only MetS trait significantly associated with UCE, while no MetS trait was associated with oxalate excretion.

  16. Gut Microbiota as a Therapeutic Target for Metabolic Disorders.

    PubMed

    Okubo, Hirofumi; Nakatsu, Yusuke; Kushiyama, Akifumi; Yamamotoya, Takeshi; Matsunaga, Yasuka; Inoue, Masa-Ki; Fujishiro, Midori; Sakoda, Hideaki; Ohno, Haruya; Yoneda, Masayasu; Ono, Hiraku; Asano, Tomoichiro

    2018-01-01

    Gut microbiota play a vital role not only in the digestion and absorption of nutrients, but also in homeostatic maintenance of host immunity, metabolism and the gut barrier. Recent evidence suggests that gut microbiota alterations contribute to the pathogenesis of metabolic disorders. In this review, we discuss the association between the gut microbiota and metabolic disorders, such as obesity, type 2 diabetes mellitus and non-alcoholic fatty liver disease, and the contribution of relevant modulating interventions, focusing on recent human studies. Several studies have identified potential causal associations between gut microbiota and metabolic disorders, as well as the underlying mechanisms. The effects of modulating interventions, such as prebiotics, probiotics, fecal microbiota transplantation, and other new treatment possibilities on these metabolic disorders have also been reported. A growing body of evidence highlights the role of gut microbiota in the development of dysbiosis, which in turn influences host metabolism and disease phenotypes. Further studies are required to elucidate the precise mechanisms by which gut microbiota-derived mediators induce metabolic disorders and modulating interventions exert their beneficial effects in humans. The gut microbiota represents a novel potential therapeutic target for a range of metabolic disorders. Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.org.

  17. MicroRNA Regulators of Anxiety and Metabolic Disorders.

    PubMed

    Meydan, Chanan; Shenhar-Tsarfaty, Shani; Soreq, Hermona

    2016-09-01

    Anxiety-related and metabolic disorders are under intense research focus. Anxiety-induced microRNAs (miRNAs) are emerging as regulators that are not only capable of suppressing inflammation but can also induce metabolic syndrome-related processes. We summarize here evidence linking miRNA pathways which share regulatory networks in metabolic and anxiety-related conditions. In particular, miRNAs involved in these disorders include regulators of acetylcholine signaling in the nervous system and their accompanying molecular machinery. These have been associated with anxiety-prone states in individuals, while also acting as inflammatory suppressors. In peripheral tissues, altered miRNA pathways can lead to dysregulated metabolism. Common pathways in metabolic and anxiety-related phenomena might offer an opportunity to reclassify 'healthy' and 'unhealthy', as well as metabolic and anxiety-prone biological states, and inform putative strategies to treat these disorders. Copyright © 2016 Elsevier Ltd. All rights reserved.

  18. Ophthalmologic Findings in Patients with Neuro-metabolic Disorders.

    PubMed

    Jafari, Narjes; Golnik, Karl; Shahriari, Mansoor; Karimzadeh, Parvaneh; Jabbehdari, Sayena

    2018-01-01

    We aimed to present the ophthalmic manifestations of neuro-metabolic disorders. Patients who were diagnosed with neuro-metabolic disorders in the Neurology Department of Mofid Pediatric Hospital in Tehran, Iran, between 2004 and 2014 were included in this study. Disorders were confirmed using clinical findings, neuroimaging, laboratory data, and genomic analyses. All enrolled patients were assessed for ophthalmological abnormalities. A total of 213 patients with 34 different neuro-metabolic disorders were included. Ophthalmological abnormalities were observed in 33.5% of patients. Abnormal findings in the anterior segment included Kayser-Fleischer rings, congenital or secondary cataracts, and lens dislocation into the anterior chamber. Posterior segment (i.e., retina, vitreous body, and optic nerve) evaluation revealed retinitis pigmentosa, cherry-red spots, and optic atrophy. In addition, strabismus, nystagmus, and lack of fixation were noted during external examination. Ophthalmological examination and assessment is essential in patients that may exhibit neuro-metabolic disorders.

  19. Alkaptonuria: a very rare metabolic disorder.

    PubMed

    Aquaron, Robert

    2013-10-01

    Alkaptonuria (AKU) is a very rare autosomal recessive disorder of tyrosine metabolism in the liver due to deficiency of homogentisate 1,2 dioxygenase (HGD) activity, resulting in the accumulation of homogentisic acid (HGA). Circulating HGA pass into various tissues through-out the body, mainly in cartilage and connective tissues, where its oxidation products polymerize and deposit as a melanin-like pigment. Gram quantities of HGA are excreted in the urine. AKU is a progressive disease and the three main features, according the chronology of appearance, are: darkening of the urine at birth, then ochronosis (blue-dark pigmentation of the connective tissue) clinically visible at around 30 yrs in the ear and eye, and finally a severe ochronotic arthropathy at around 50 yrs with spine and large joints involvements. Cardiovascular and renal complications have been described in numerous case report studies. A treatment now is available in the form of a drug nitisinone, which decreases the production of HGA. The enzymatic defect in AKU is caused by the homozygous or compound heterozygous mutations within the HGD gene. This disease has a very low prevalence (1:100,000-250,000) in most of the ethnic groups, except Slovakia and Dominican Republic, where the incidence has shown increase up to 1:19,000. This review highlights classical and recent findings on this very rare disease.

  20. Role of calcium in phosphoinositide metabolism and inhibition of norepinephrine transport into synaptic vesicles by amphetamine analogs

    SciTech Connect

    Knepper, S.M.

    1985-01-01

    Norepinephrine-(NE) and calcium ionophore A23187-stimulated phosphoinositide (PIn) metabolism in rat brain slices was studied under varying calcium conditions. Tissue was labelled with /sup 3/H-myo-inositol and /sup 3/H-inositol phosphates (IPn), products of PIn metabolism were measured. In the absence of media calcium the response to NE was decreased while that to A23187 was little affected A23187 can release calcium from intracellular stores. Basal and stimulated accumulation of /sup 3/H-IPn was reversibly antagonized with EGTA by addition of calcium. Using calcium buffers, approximately 10/sup -7/ M free calcium was required to support hydrolysis. Free intracellular calcium is maintained at approximately this level.more » Thus calcium is required for PIn hydrolysis but appears to play a permissive role, basal levels being sufficient to support metabolism. Conformationally-defined (rigid) and -restricted (semi-rigid) analogs of the most stable conformations of amphetamine, antiperiplanar (exo) and gauche (endo), were utilized to probe the conformational requirements of vesicular NE transport. Analogs tested were 2-aminotetralin (2AT), 3-methyltetrahydroisoquinoline, anti- and syn-9-aminobenzobicyclo(2.2.1)heptene, and endo and exo conformers of 2-aminobenzobicyclo(2.2.1)heptene and 2-aminobenzobicyclo(2.2.2)octene.« less

  1. Effects of prepartum dietary calcium level on calcium and magnesium metabolism in periparturient dairy cows.

    PubMed

    Kronqvist, C; Emanuelson, U; Spörndly, R; Holtenius, K

    2011-03-01

    The aim of this study was to investigate the effects of dietary Ca level (4.9, 9.3, and 13.6 g/kg of DM) on Ca and Mg homeostasis in dairy cows around parturition. Cows of the Swedish Red breed (n = 29) with no previous veterinary treatment for milk fever were divided into 3 groups, and each group was fed one of the different diets during the last 15 to 32 d of gestation. Calcium was added as ground limestone, and the Mg concentration was 1.8 g/kg of DM in all diets. After calving the cows were fed similar diets. Plasma was sampled twice per week until calving, and 6, 12, and 24 h, 2, 4, and 7 d after calving. Spot urine samples were collected twice weekly until calving and creatinine was used as a marker of daily urinary excretion. Fecal samples were collected 2 times per day for 5 d starting 2 wk before expected calving, and acid-insoluble ash was used as an indigestible marker to estimate digestibility. Apparent digestibility of Mg and daily Mg excretion in the urine were lower in the dry period for cows fed the highest Ca level. Plasma Mg concentration was lower on 2, 4, and 7 d after calving in cows fed the highest level of Ca. Treatment groups did not differ in plasma Ca concentration, parathyroid hormone concentration, or bone mobilization, evaluated using crosslinked carboxyterminal telopeptides of type I collagen (CTx) as a marker. Plasma Ca concentration decreased and plasma CTx concentration increased 6 h after calving. The apparent digestibility of Ca during the dry period was not affected by dietary Ca, but the cows fed 4.9 g Ca/kg of DM excreted 1.2 g of Ca/d in the urine, which was higher compared with 0.4 g/d and 0.6 g/d for the cows fed 9.3 g of Ca/kg of DM and 13.6 g of Ca/kg of DM, respectively. The results show that feeding 13.6 g of dietary Ca/kg of DM impaired the Mg absorption during the dry period, and resulted in decreased plasma Mg concentration after calving, but prepartum dietary Ca level did not affect plasma Ca, parathyroid hormone, or

  2. Treating mineral metabolism disorders in patients undergoing long hemodialysis: a search for an optimal strategy.

    PubMed

    Jean, Guillaume; Vanel, Thierry; Terrat, Jean-Claude; Hurot, Jean-Marc; Lorriaux, Christie; Mayor, Brice; Chazot, Charles

    2009-10-01

    In hemodialysis (HD) patients, mineral metabolism (MM) disorders have been associated with an increased mortality rate. We report the evolution of MM parameters in a stable HD population undergoing long hemodialysis by performing an annual cross-sectional analysis for every year from 1994 to 2008. The therapeutic strategy has changed: the dialysate calcium concentration has decreased from a mean of 1.7 +/- 0.1 to 1.5 +/- 0.07 mmol/L and has been adapted to parathyroid hormone serum levels (from 1 to 1.75 mmol/L). The use of calcium-based and aluminum-based phosphate binders has decreased and they have been replaced by sevelamer; alfacalcidol has partly been replaced by native vitamin D. The percentage of patients with a parathyroid hormone serum level between 150 and 300 pg/mL has increased from 9% to 67% (P<0.001); the percentage of patients with phosphataemia between 1.15 and 1.78 mmol/L has increased from 39% to 84% (P<0.001). The percentage of those with albumin-corrected calcemia between 2.1 and 2.37 mmol/L has increased from 29% to 61% (P<0.001), and that of patients with a calcium-phosphorous product (Ca x P) level >4.4 mmol/L decreased from 8.8% to 2% (P=0.02). Although patients undergo long and intensive HD treatment, MM disorders are common. However, an appropriate strategy, mostly consisting of native vitamin D supplementation, progressive replacement of calcium-based phosphate binders with non-calcium-based ones, and individualization of dialysis session duration and dialysate calcium concentration, would result in a drastic improvement.

  3. The influence of calcium supplementation on substrate metabolism during exercise in humans: a randomized controlled trial.

    PubMed

    Gonzalez, J T; Green, B P; Campbell, M D; Rumbold, P L S; Stevenson, E J

    2014-06-01

    High calcium intakes enhance fat loss under restricted energy intake. Mechanisms explaining this may involve reduced dietary fat absorption, enhanced lipid utilization and (or) reductions in appetite. This study aimed to assess the impact of 2 weeks of calcium supplementation on substrate utilization during exercise and appetite sensations at rest. Thirteen physically active males completed two 14-d supplemental periods, in a double-blind, randomized crossover design separated by a ⩾4-week washout period. During supplementation, a test-drink was consumed daily containing 400 and 1400 mg of calcium during control (CON) and high-calcium (CAL) periods, respectively. Cycling-based exercise tests were conducted before and after each supplemental period to determine substrate utilization rates and circulating metabolic markers (non-esterified fatty acid, glycerol, glucose and lactate concentrations) across a range of exercise intensities. Visual analog scales were completed in the fasting, rested state to determine subjective appetite sensations. No significant differences between supplements were observed in lipid or carbohydrate utilization rates, nor in circulating metabolic markers (both P>0.05). Maximum rates of lipid utilization were 0.47±0.05 and 0.44±0.05 g/min for CON and CAL, respectively, prior to supplementation and 0.44±0.05 and 0.42±0.05 g/min, respectively, post-supplementation (main effects of time, supplement and time x supplement interaction effect all P>0.05). Furthermore, no significant differences were detected in any subjective appetite sensations (all P>0.05). Two weeks of calcium supplementation does not influence substrate utilization during exercise in physically active males.

  4. Cerebral glucose metabolic differences in patients with panic disorder

    SciTech Connect

    Nordahl, T.E.; Semple, W.E.; Gross, M.

    Regional glucose metabolic rates were measured in patients with panic disorder during the performance of auditory discrimination. Those regions examined by Reiman and colleagues in their blood flow study of panic disorder were examined with a higher resolution positron emission tomography (PET) scanner and with the tracer (F-18)-2-fluoro-2-deoxyglucose (FDG). In contrast to the blood flow findings of Reiman et al., we did not find global gray metabolic differences between patients with panic disorder and normal controls. Consistent with the findings of Reiman et al., we found hippocampal region asymmetry. We also found metabolic decreases in the left inferior parietal lobulemore » and in the anterior cingulate (trend), as well as an increase in the metabolic rate of the medial orbital frontal cortex (trend) of panic disorder patients. It is unclear whether the continuous performance task (CPT) enhanced or diminished findings that would have been noted in a study performed without task.« less

  5. Glucose Metabolism Disorders, HIV and Antiretroviral Therapy among Tanzanian Adults

    PubMed Central

    Maganga, Emmanuel; Smart, Luke R.; Kalluvya, Samuel; Kataraihya, Johannes B.; Saleh, Ahmed M.; Obeid, Lama; Downs, Jennifer A.; Fitzgerald, Daniel W.; Peck, Robert N.

    2015-01-01

    Introduction Millions of HIV-infected Africans are living longer due to long-term antiretroviral therapy (ART), yet little is known about glucose metabolism disorders in this group. We aimed to compare the prevalence of glucose metabolism disorders among HIV-infected adults on long-term ART to ART-naïve adults and HIV-negative controls, hypothesizing that the odds of glucose metabolism disorders would be 2-fold greater even after adjusting for possible confounders. Methods In this cross-sectional study conducted between October 2012 and April 2013, consecutive adults (>18 years) attending an HIV clinic in Tanzania were enrolled in 3 groups: 153 HIV-negative controls, 151 HIV-infected, ART-naïve, and 150 HIV-infected on ART for ≥ 2 years. The primary outcome was the prevalence of glucose metabolism disorders as determined by oral glucose tolerance testing. We compared glucose metabolism disorder prevalence between each HIV group vs. the control group by Fisher’s exact test and used multivariable logistic regression to determine factors associated with glucose metabolism disorders. Results HIV-infected adults on ART had a higher prevalence of glucose metabolism disorders (49/150 (32.7%) vs.11/153 (7.2%), p<0.001) and frank diabetes mellitus (27/150 (18.0%) vs. 8/153 (5.2%), p = 0.001) than HIV-negative adults, which remained highly significant even after adjusting for age, gender, adiposity and socioeconomic status (OR = 5.72 (2.78–11.77), p<0.001). Glucose metabolism disorders were significantly associated with higher CD4+ T-cell counts. Awareness of diabetes mellitus was <25%. Conclusions HIV-infected adults on long-term ART had 5-fold greater odds of glucose metabolism disorders than HIV-negative controls but were rarely aware of their diagnosis. Intensive glucose metabolism disorder screening and education are needed in HIV clinics in sub-Saharan Africa. Further research should determine how glucose metabolism disorders might be related to immune

  6. Peroxisome Proliferators-Activated Receptor (PPAR) Modulators and Metabolic Disorders

    PubMed Central

    Cho, Min-Chul; Lee, Kyoung; Paik, Sang-Gi; Yoon, Do-Young

    2008-01-01

    Overweight and obesity lead to an increased risk for metabolic disorders such as impaired glucose regulation/insulin resistance, dyslipidemia, and hypertension. Several molecular drug targets with potential to prevent or treat metabolic disorders have been revealed. Interestingly, the activation of peroxisome proliferator-activated receptor (PPAR), which belongs to the nuclear receptor superfamily, has many beneficial clinical effects. PPAR directly modulates gene expression by binding to a specific ligand. All PPAR subtypes (α, γ, and σ) are involved in glucose metabolism, lipid metabolism, and energy balance. PPAR agonists play an important role in therapeutic aspects of metabolic disorders. However, undesired effects of the existing PPAR agonists have been reported. A great deal of recent research has focused on the discovery of new PPAR modulators with more beneficial effects and more safety without producing undesired side effects. Herein, we briefly review the roles of PPAR in metabolic disorders, the effects of PPAR modulators in metabolic disorders, and the technologies with which to discover new PPAR modulators. PMID:18566691

  7. Genetic disorders of thyroid metabolism and brain development

    PubMed Central

    Kurian, Manju A; Jungbluth, Heinz

    2014-01-01

    Normal thyroid metabolism is essential for human development, including the formation and functioning of the central and peripheral nervous system. Disorders of thyroid metabolism are increasingly recognized within the spectrum of paediatric neurological disorders. Both hypothyroid and hyperthyroid disease states (resulting from genetic and acquired aetiologies) can lead to characteristic neurological syndromes, with cognitive delay, extrapyramidal movement disorders, neuropsychiatric symptoms, and neuromuscular manifestations. In this review, the neurological manifestations of genetic disorders of thyroid metabolism are outlined, with particular focus on Allan-Herndon-Dudley syndrome and benign hereditary chorea. We report in detail the clinical features, major neurological and neuropsychiatric manifestations, molecular genetic findings, disease mechanisms, and therapeutic strategies for these emerging genetic ‘brain-thyroid’ disorders. PMID:24665922

  8. Diagnosis of Disorders of Iron Metabolism in Dogs and Cats.

    PubMed

    Bohn, Andrea A

    2015-09-01

    Iron is an essential element and is used by every cell in the body. This article summarizes iron metabolism and disorders associated with iron metabolism in dogs and cats. The diagnostic tests currently in use for assessing iron status are discussed. Copyright © 2015 Elsevier Inc. All rights reserved.

  9. Genetic disruption of voltage-gated calcium channels in psychiatric and neurological disorders

    PubMed Central

    Heyes, Samuel; Pratt, Wendy S.; Rees, Elliott; Dahimene, Shehrazade; Ferron, Laurent; Owen, Michael J.; Dolphin, Annette C.

    2015-01-01

    This review summarises genetic studies in which calcium channel genes have been connected to the spectrum of neuropsychiatric syndromes, from bipolar disorder and schizophrenia to autism spectrum disorders and intellectual impairment. Among many other genes, striking numbers of the calcium channel gene superfamily have been implicated in the aetiology of these diseases by various DNA analysis techniques. We will discuss how these relate to the known monogenic disorders associated with point mutations in calcium channels. We will then examine the functional evidence for a causative link between these mutations or single nucleotide polymorphisms and the disease processes. A major challenge for the future will be to translate the expanding psychiatric genetic findings into altered physiological function, involvement in the wider pathology of the diseases, and what potential that provides for personalised and stratified treatment options for patients. PMID:26386135

  10. Functional Effects of Prebiotic Fructans in Colon Cancer and Calcium Metabolism in Animal Models.

    PubMed

    Rivera-Huerta, Marisol; Lizárraga-Grimes, Vania Lorena; Castro-Torres, Ibrahim Guillermo; Tinoco-Méndez, Mabel; Macías-Rosales, Lucía; Sánchez-Bartéz, Francisco; Tapia-Pérez, Graciela Guadalupe; Romero-Romero, Laura; Gracia-Mora, María Isabel

    2017-01-01

    Inulin-type fructans are polymers of fructose molecules and are known for their capacity to enhance absorption of calcium and magnesium, to modulate gut microbiota and energy metabolism, and to improve glycemia. We evaluated and compared the effects of Chicory inulin "Synergy 1®" and inulin from Mexican agave "Metlin®" in two experimental models of colon cancer and bone calcium metabolism in mice and rats. Inulins inhibited the development of dextran sulfate sodium-induced colitis and colon cancer in mice; these fructans reduced the concentration of tumor necrosis factor alpha and prevented the formation of intestinal polyps, villous atrophy, and lymphoid hyperplasia. On the other hand, inulin treatments significantly increased bone densitometry (femur and vertebra) in ovariectomized rats without altering the concentration of many serum biochemical parameters and urinary parameters. Histopathology results were compared between different experimental groups. There were no apparent histological changes in rats treated with inulins and a mixture of inulins-isoflavones. Our results showed that inulin-type fructans have health-promoting properties related to enhanced calcium absorption, potential anticancer properties, and anti-inflammatory effects. The use of inulin as a prebiotic can improve health and prevent development of chronic diseases such as cancer and osteoporosis.

  11. Diagnosis and treatment of common metabolic spinal disorders in the geriatric population.

    PubMed

    Eck, J C; Humphreys, S C

    1998-12-01

    Bone is constantly resorbed and remodeled throughout life. After approximately age 30, there is a net loss of bone mass. This places the geriatric population at an increased risk of pathologic bone disorders that can lead to fractures and deformity. In this paper, we review bone metabolism and remodeling and introduce the proper diagnostic techniques. The most common pathologic spinal disorders are introduced, with emphasis on presentation and treatment options. To prevent excessive bone loss, patients should be educated on proper nutrition (calcium and vitamin D requirements) and lifestyle (avoiding alcohol and cigarette smoking). Sex hormone and drug therapies are available to reduce bone loss. New bisphosphonates such as alendronate sodium (Fosamax) have been effective in increasing bone mass. Early diagnosis and proper treatment of pathologic bone disorders can reduce the incidence of fracture and allow the patient a more productive and comfortable life.

  12. Vitamin D Status and Calcium Metabolism in Adolescent Black and White Girls on a Range of Controlled Calcium Intakes

    PubMed Central

    Weaver, Connie M.; McCabe, Linda D.; McCabe, George P.; Braun, Michelle; Martin, Berdine R.; DiMeglio, Linda A.; Peacock, Munro

    2008-01-01

    Background: There are limited data in adolescents on racial differences in relationships between dietary calcium intake, absorption, and retention and serum levels of calcium-regulating hormones. Objectives: The aim of this study was to investigate these relationships cross-sectionally in American White and Black adolescent girls. Methods: Calcium balance studies were conducted in 105 girls, aged 11–15 yr, on daily calcium intakes ranging from 760–2195 mg for 3-wk controlled feeding periods; 158 observations from 52 Black and 53 White girls were analyzed. Results: Black girls had lower serum 25-hydroxyvitamin D [25(OH)D], higher serum 1,25-dihydroxyvitamin D, and higher calcium absorption and retention than White girls. Calcium intake and race, but not serum 25(OH)D, predicted net calcium absorption and retention with Black girls absorbing calcium more efficiently at low calcium intakes than White girls. The relationship between serum 25(OH)D and serum PTH was negative only in White girls. Calcium intake, race, and postmenarcheal age explained 21% of the variation in calcium retention, and serum 25(OH)D did not contribute further to the variance. Conclusions: These results suggest that serum 25(OH)D does not contribute to the racial differences in calcium absorption and retention during puberty. PMID:18682505

  13. Calcium-regulated nuclear enzymes: potential mediators of phytochrome-induced changes in nuclear metabolism?

    NASA Technical Reports Server (NTRS)

    Roux, S. J.

    1992-01-01

    Calcium ions have been proposed to serve as important regulatory elements in stimulus-response coupling for phytochrome responses. An important test of this hypothesis will be to identify specific targets of calcium action that are required for some growth or development process induced by the photoactivated form of phytochrome (Pfr). Initial studies have revealed that there are at least two enzymes in pea nuclei that are stimulated by Pfr in a Ca(2+)-dependent fashion, a calmodulin-regulated nucleoside triphosphatase and a calmodulin-independent but Ca(2+)-dependent protein kinase. The nucleoside triphosphatase appears to be associated with the nuclear envelope, while the protein kinase co-purifies with a nuclear fraction highly enriched for chromatin. This short review summarizes the latest findings on these enzymes and relates them to what is known about Pfr-regulated nuclear metabolism.

  14. Metabolic diagnosis and medical prevention of calcium nephrolithiasis and its systemic manifestations: a consensus statement.

    PubMed

    Gambaro, Giovanni; Croppi, Emanuele; Coe, Fredric; Lingeman, James; Moe, Orson; Worcester, Elen; Buchholz, Noor; Bushinsky, David; Curhan, Gary C; Ferraro, Pietro Manuel; Fuster, Daniel; Goldfarb, David S; Heilberg, Ita Pfeferman; Hess, Bernard; Lieske, John; Marangella, Martino; Milliner, Dawn; Preminger, Glen M; Reis Santos, Jose' Manuel; Sakhaee, Khashayar; Sarica, Kemal; Siener, Roswitha; Strazzullo, Pasquale; Williams, James C

    2016-12-01

    Recently published guidelines on the medical management of renal stone disease did not address relevant topics in the field of idiopathic calcium nephrolithiasis, which are important also for clinical research. A steering committee identified 27 questions, which were proposed to a faculty of 44 experts in nephrolithiasis and allied fields. A systematic review of the literature was conducted and 5216 potentially relevant articles were selected; from these, 407 articles were deemed to provide useful scientific information. The Faculty, divided into working groups, analysed the relevant literature. Preliminary statements developed by each group were exhaustively discussed in plenary sessions and approved. Statements were developed to inform clinicians on the identification of secondary forms of calcium nephrolithiasis and systemic complications; on the definition of idiopathic calcium nephrolithiasis; on the use of urinary tests of crystallization and of surgical observations during stone treatment in the management of these patients; on the identification of patients warranting preventive measures; on the role of fluid and nutritional measures and of drugs to prevent recurrent episodes of stones; and finally, on the cooperation between the urologist and nephrologist in the renal stone patients. This document has addressed idiopathic calcium nephrolithiasis from the perspective of a disease that can associate with systemic disorders, emphasizing the interplay needed between urologists and nephrologists. It is complementary to the American Urological Association and European Association of Urology guidelines. Future areas for research are identified.

  15. Exaggerated levothyroxine malabsorption due to calcium carbonate supplementation in gastrointestinal disorders.

    PubMed

    Csako, G; McGriff, N J; Rotman-Pikielny, P; Sarlis, N J; Pucino, F

    2001-12-01

    To describe a patient with primary hypothyroidism in whom ingestion of levothyroxine with calcium carbonate led to markedly elevated serum thyrotropin concentrations. A 61-year-old white woman with primary hypothyroidism, systemic lupus erythematosus, celiac disease, and history of Whipple resection for pancreatic cancer was euthyroid with levothyroxine 175-188 micrograms/d. After taking a high dose of calcium carbonate (1250 mg three times daily) with levothyroxine, she developed biochemical evidence of hypothyroidism (thyrotropin up to 41.4 mU/L) while remaining clinically euthyroid. Delaying calcium carbonate administration by four hours returned her serum thyrotropin to a borderline high concentration (5.7 mU/L) within a month. Serum concentrations of unbound and total thyroxine and triiodothyronine tended to decrease, but remained borderline low to normal while the patient concomitantly received levothyroxine and calcium carbonate. Concomitant administration of levothyroxine and calcium carbonate often results in levothyroxine malabsorption. While in most patients the clinical consequences of this interaction, even with prolonged exposure, are relatively small, overt hypothyrodism may develop in patients with preexisting malabsorption disorders. However, as the current case illustrates, the clinical manifestations of the initial levothyroxine deficit may not always be apparent and, of all usual laboratory thyroid function tests, only thyrotropin measurement will reliably uncover the exaggerated levothyroxine malabsorption. Decreased absorption of levothyroxine when given with calcium carbonate may be particularly pronounced in patients with preexisting malabsorption disorders. Once recognized, a change in drug administration schedule usually minimizes or eliminates this interaction.

  16. Ultrasound enhances calcium absorption of jujube fruit by regulating the cellular calcium distribution and metabolism of cell wall polysaccharides.

    PubMed

    Zhi, Huanhuan; Liu, Qiqi; Xu, Juan; Dong, Yu; Liu, Mengpei; Zong, Wei

    2017-12-01

    Ultrasound has been applied in fruit pre-washing processes. However, it is not sufficient to protect fruit from pathogenic infection throughout the entire storage period, and sometimes ultrasound causes tissue damage. The goal of this study was to investigate the effects of calcium chloride (CaCl 2 , 10 g L -1 ) and ultrasound (350 W at 40 kHz), separately and in combination, on jujube fruit quality, antioxidant status, tissue Ca 2+ content and distribution along with cell wall metabolism at 20 °C for 6 days. All three treatments significantly maintained fruit firmness and peel color, reduced respiration rate, decay incidence, superoxide anion, hydrogen peroxide and malondialdehyde and preserved higher enzymatic (superoxide dismutase, catalase and peroxidase) and non-enzymatic (ascorbic acid and glutathione) antioxidants compared with the control. Moreover, the combined treatment was more effective in increasing tissue Ca 2+ content and distribution, inhibiting the generation of water-soluble and CDTA-soluble pectin fractions, delaying the solubilization of Na 2 CO 3 -soluble pectin and having lower activities of cell wall-modifying enzymes (polygalacturonase and pectate lyase) during storage. These results demonstrated that the combination of CaCl 2 and ultrasound has potential commercial application to extend the shelf life of jujube fruit by facilitating Ca 2+ absorption and stabilizing the cell wall structure. © 2017 Society of Chemical Industry. © 2017 Society of Chemical Industry.

  17. Bone Mineral Density Accrual in Students with Autism Spectrum Disorders: Effects of Calcium Intake and Physical Training

    ERIC Educational Resources Information Center

    Goodarzi, Mahmood; Hemayattalab, Rasool

    2012-01-01

    The purpose of this study was to investigate the effects of weight bearing exercise and calcium intake on bone mineral density (BMD) of students with autism spectrum disorders. For this reason 60 boy students with autism disorder (age 8-10 years old) were assigned to four groups with no differences in age, BMD, calcium intake, and physical…

  18. Fitness attenuates the prevalence of increased coronary artery calcium in individuals with metabolic syndrome.

    PubMed

    Ekblom-Bak, Elin; Ekblom, Örjan; Fagman, Erika; Angerås, Oskar; Schmidt, Caroline; Rosengren, Annika; Börjesson, Mats; Bergström, Göran

    2018-02-01

    Background The association between cardiorespiratory fitness, physical activity and coronary artery calcium (CAC) is unclear, and whether higher levels of fitness attenuate CAC prevalence in subjects with metabolic syndrome is not fully elucidated. The present study aims to: a) investigate the independent association of fitness on the prevalence of CAC, after adjustment for moderate-to-vigorous physical activity and sedentary time, and b) study the possible attenuation of increased CAC by higher fitness, in participants with metabolic syndrome. Design Cross-sectional. Methods In total 678 participants (52% women), 50-65 years old, from the SCAPIS pilot study were included. Fitness (VO 2 max) was estimated by submaximal cycle ergometer test and moderate-to-vigorous physical activity and sedentary time were assessed using hip-worn accelerometers. CAC score (CACS) was quantified using the Agatston score. Results The odds of having a significant CACS (≥100) was half in participants with moderate/high fitness compared with their low fitness counterparts. Further consideration of moderate-to-vigorous physical activity, sedentary time and number of components of the metabolic syndrome did only slightly alter the effect size. Those with metabolic syndrome had 47% higher odds for significant CAC compared with those without metabolic syndrome. However, moderate/high fitness seems to partially attenuate this risk, as further joint analysis indicated an increased odds for having significant CAC only in the unfit metabolic syndrome participants. Conclusions Being fit is associated with a reduced risk of having significant CAC in individuals with metabolic syndrome. While still very much underutilized, fitness should be taken into consideration in everyday clinical risk prediction in addition to the traditional risk factors of the metabolic syndrome.

  19. FGF23 and Klotho: the new cornerstones of phosphate/calcium metabolism

    PubMed Central

    Bacchetta, Justine; Cochat, Pierre; Salusky, Isidro B

    2014-01-01

    Since its first description as a phosphaturic agent in the early 2000’s, the Fibroblast Growth Factor 23 (FGF23) has rapidly become the third key player of phosphate/calcium metabolism with the two ‘old’ PTH and vitamin D. FGF23 is a protein synthesized by osteocytes that acts mainly as a phosphaturic factor and a suppressor of 1α hydroxylase activity in the kidney. It inhibits the expression of type IIa and IIc sodium-phosphate cotransporters on the apical membrane of proximal tubular cells, thus leading to an inhibition of phosphate reabsorption. Moreover, it also inhibits the 1α hydroxylase activity. These two renal pathways account together for the hypophosphatemic effect of FGF23, but FGF23 has also been recently described as an inhibiting factor for PTH synthesis. Its exact role in bone remains to be defined. A transmembrane protein, Klotho, is an essential cofactor for FGF23 biological activity, but it can also act by itself for calcium and PTH regulation. This paper gives an overview of these recent data of phosphate/calcium physiology, as well as a description of clinical conditions associated with FGF23 deregulation (genetic diseases and chronic kidney disease). As a conclusion, future therapeutic consequences of the FGF23/Klotho axis are discussed. PMID:21497493

  20. Tinnitus sensation pre and post nutritional intervention in metabolic disorders.

    PubMed

    Almeida, Thamine Andrade Siqueira; Samelli, Alessandra Giannella; Mecca, Fabíola Del Nero; De Martino, Eliana; Paulino, Adriana Machado

    2009-01-01

    Different etiologies are related to tinnitus including metabolic disorders (blood glucose and lipids). The aim of this study was compare tinnitus severity by self-report measures pre and post nutritional intervention, using the Tinnitus Handicap Inventory. Participants of this study were twenty one male and female subjects, with ages ranging from 40 to 82 years. Inclusion criteria involved the presence of tinnitus and metabolic disorder diagnosed by laboratory exams. All subjects were submitted to a nutritional intervention program. Audiological evaluation and the Tinnitus Handicap Inventory were applied pre and post intervention. When comparing the presence of tinnitus pre and post intervention, data analysis indicates statistical difference concerning tinnitus sensation--71.5% of the individuals referred less impact of tinnitus in daily activities. An important difference was observed concerning tinnitus influence in subject's life by self-report measures. A direct relation between tinnitus and metabolic disorders in cases related with this symptom was verified.

  1. Disorders of fuel metabolism: medical complications associated with starvation, eating disorders, dietary fads, and supplements.

    PubMed

    Judge, Bryan S; Eisenga, Bernard H

    2005-08-01

    Disorders of fuel metabolism as they relate to abnormal fuel intake,abnormal fuel expenditure, and dietary supplements are the focus of this article. The emergency physician should be aware of the medical complications that can occur as a result of starvation states,eating disorders, fad diets, hypermetabolic states, and ergogenic aids. Knowledge and understanding of the complications associated with these disorders will facilitate the diagnosis and management of patients who present to the emergency department with any of the disorders reviewed.

  2. Microgravity Effecs During Fertilization, Cell Division, Development, and Calcium Metabolism in Sea Urchins

    NASA Technical Reports Server (NTRS)

    Schatten, Heide

    1999-01-01

    Calcium loss and muscle atrophy are two of the main metabolic changes experienced by astronauts and crew members during exposure to microgravity in space. For long-term exposure to space it is crucial to understand the underlying mechanisms for altered physiological functions. Fundamental occurrences in cell biology which are likely to depend on gravity include cytoskeletal dynamics, chromatin and centrosome cycling, and ion immobilization. These events can be studied during fertilization and embryogenesis within invertebrate systems. We have chosen the sea urchin system to study the effects of microgravity on cytoskeletal processes and calcium metabolism during fertilization, cell division, development, and embryogenesis. Experiments during an aircraft parabolic flight (KC-135) demonstrated: (1) the viability of sea urchin eggs prior to fertilization, (2) the suitability of our specimen containment system, (3) the feasibility of fertilization in a reduced gravity environment (which was achieved during 25 seconds of reduced gravity under parabolic flight conditions). Two newly developed pieces of spaceflight hardware made further investigations possible on a spaceflight (STS-77); (1) the Aquatic Research Facility (ARF), and (2) the Fertilization Syringe Unit (FSU). The Canadian Space Agency developed ARF to conduct aquatic spaceflight experiments requiring controlled conditions of temperature, humidity, illumination, and fixation at predetermined time points. It contained a control centrifuge which simulated the 1 g environment of earth during spaceflight. The FSU was developed at the Kennedy Space Center (KSC) by the Bionetics Corporation specifically to enable the crew to perform sea urchin fertilization operations in space.

  3. Milrinone and levosimendan during porcine myocardial ischemia -- no effects on calcium overload and metabolism.

    PubMed

    Axelsson, B; Johansson, G; Abrahamsson, P; Gupta, A; Tydén, H; Wouters, P; Haney, M

    2013-07-01

    Although inotropic stimulation is considered harmful in the presence of myocardial ischaemia, both calcium sensitisers and phosphodiesterase inhibitors may offer cardioprotection. We hypothesise that these cardioprotective effects are related to an acute alteration of myocardial metabolism. We studied in vivo effects of milrinone and levosimendan on calcium overload and ischaemic markers using left ventricular microdialysis in pigs with acute myocardial ischaemia. Anaesthetised juvenile pigs, average weight 36 kg, were randomised to one of three intravenous treatment groups: milrinone 50 μg/kg bolus plus infusion 0.5 μg/kg/min (n = 7), levosimendan 24 μg/kg plus infusion 0.2 μg/kg/min (n = 7), or placebo (n = 6) for 60 min prior to and during a 45 min acute regional coronary occlusion. Systemic and myocardial haemodynamics were assessed, and microdialysis was performed with catheters positioned in the left ventricular wall. (45) Ca(2+) was included in the microperfusate in order to assess local calcium uptake into myocardial cells. The microdialysate was analysed for glucose, lactate, pyruvate, glycerol, and for (45) Ca(2+) recovery. During ischaemia, there were no differences in microdialysate-measured parameters between control animals and milrinone- or levosimendan-treated groups. In the pre-ischaemic period, arterial blood pressure decreased in all groups while myocardial oxygen consumption remained stable. These findings reject the hypothesis of an immediate energy-conserving effect of milrinone and levosimendan during acute myocardial ischaemia. On the other hand, the data show that inotropic support with milrinone and levosimendan does not worsen the metabolic parameters that were measured in the ischaemic myocardium. © 2013 The Acta Anaesthesiologica Scandinavica Foundation. Published by John Wiley & Sons Ltd.

  4. Novel function of the skin in calcium metabolism in female and male chickens (Gallus domesticus).

    PubMed

    Peltonen, Liisa M; Sankari, Satu; Kivimäki, Anneli; Autio, Pekka

    2006-08-01

    To study the role of the skin in differential calcium metabolism in White Leghorn chickens, we compared the composition of suction blister fluid (SBF) collected from cutaneous blisters with blood and serum in female and male animals in various physiological states. As an estimate for interstitial fluid (IF), SBF was used as a determinant of local cutaneous metabolism. Sample collection was carried out under ketamine-xylazine anesthesia. Eight chickens of both sexes were raised freely in similar environmental conditions and fed with similar food during their growth from juvenile to sexually mature and fully adult state. SBF, blood and serum were examined for concentrations of ionized Ca2+, Na+ and K+ with ion-selective electrodes (ISEs), and osmolalities by freezing point osmometry. pH and total protein content were also assessed. Our results showed that SBF of chickens is calcium-poor at the juvenile state and that it draws more Ca2+ in adult males than laying females of the same age. Interestingly, Ca2+ accumulation was observed also in females after laying had ceased. There was a positive correlation between blood and SBF Ca2+ in females but a negative one in males. In general, it was found that SBF of chickens was rich in Na+ and K+, was hypertonic compared to serum at the juvenile state and had a protein content of 36-47% of that in serum. Different from mammals, SBF in adult chickens was alkaline with the mean values of 8.7+/-0.14 in females and 8.8+/-0.06 in males. Age- and sex-related variability in cutaneous Ca2+ concentrations in chickens, and the differences of SBF composition between that of mammals point to a novel role of skin functions in avians. Possible functions of the skin as a dynamic calcium source balancing the free circulating Ca2+ levels and, also, as an excretory organ for Ca2+ are discussed.

  5. Calcium ion binding properties and the effect of phosphorylation on the intrinsically disordered Starmaker protein.

    PubMed

    Wojtas, Magdalena; Hołubowicz, Rafał; Poznar, Monika; Maciejewska, Marta; Ożyhar, Andrzej; Dobryszycki, Piotr

    2015-10-27

    Starmaker (Stm) is an intrinsically disordered protein (IDP) involved in otolith biomineralization in Danio rerio. Stm controls calcium carbonate crystal formation in vivo and in vitro. Phosphorylation of Stm affects its biomineralization properties. This study examined the effects of calcium ions and phosphorylation on the structure of Stm. We have shown that CK2 kinase phosphorylates 25 or 26 residues in Stm. Furthermore, we have demonstrated that Stm's affinity for calcium binding is dependent on its phosphorylation state. Phosphorylated Stm (StmP) has an estimated 30 ± 1 calcium binding sites per protein molecule with a dissociation constant (KD) of 61 ± 4 μM, while the unphosphorylated protein has 28 ± 3 sites and a KD of 210 ± 22 μM. Calcium ion binding induces a compaction of the Stm molecule, causing a significant decrease in its hydrodynamic radius and the formation of a secondary structure. The screening effect of Na(+) ions on calcium binding was also observed. Analysis of the hydrodynamic properties of Stm and StmP showed that Stm and StmP molecules adopt the structure of native coil-like proteins.

  6. [Metabolic syndrome and bipolar disorder: Is sleep the missing link?

    PubMed

    Brochard, H; Boudebesse, C; Henry, C; Godin, O; Leboyer, M; Étain, B

    2016-12-01

    To examine the pathophysiologic mechanisms that may link circadian disorder and metabolic syndrome in bipolar disorder (BP). A systematic review of the literature was conducted from January 2013 to January 2015, using the Medline and Cochrane databases, using the keywords "metabolic syndrome", "obesity", "leptin" and "circadian disorders", "sleeping disorders" and cross-referencing them with "bipolar disorder". The following types of publications were candidates for review: (i) clinical trials; (ii) studies involving patients diagnosed with bipolar disorder; (iii) studies involving patients with sleeping disorder; or (iv) data about metabolic syndrome. Forty articles were selected. The prevalence of metabolic syndrome in BP was significantly higher compared to the general population (from 36 to 49% in the USA [Vancampfort, 2013]), and could be explained by several factors including reduced exercise and poor diet, genetic vulnerability, frequent depressive episodes, psychiatric comorbidity and psychotropic treatment. This high frequency of metabolic syndrome worsens the prognosis of these patients, increasing morbidity and mortality. Secondly, patients with BP experienced circadian and sleep disturbance, including modification in melatonin secretion. These perturbations are known to persist in periods of mood stabilization and are found in patients' relatives. Circadian disturbances are factors of relapse in bipolar patients, and they may also have a role in the metabolic comorbidities of these patients. Recent studies show that in populations of patients with bipolar disorder, a correlation between circadian disturbance and metabolic parameters are found. To identify the pathophysiological pathway connecting both could lead to a better comprehension of the disease and new therapeutics. In the overall population, mechanisms have been identified linking circadian and metabolic disorder involving hormones like leptin and ghrelin. These hormones are keys to

  7. CEREBRAL BLOOD FLOW AND METABOLISM IN ANXIETY AND ANXIETY DISORDERS

    PubMed Central

    Mathew, Roy J.

    1994-01-01

    Anxiety disorders are some of the commonest psychiatric disorders and anxiety commonly co-exists with other psychiatric conditions. Anxiety can also be a normal emotion. Thus, study of the neurobiological effects of anxiety is of considerable significance. In the normal brain, cerebral blood flow (CBF) and metabolism (CMR) serve as indices of brain function. CBF/CMR research is expected to provide new insight into alterations in brain function in anxiety disorders and other psychiatric disorders. Possible associations between stress I anxiety I panic and cerebral ischemia I stroke give additional significance to the effects of anxiety on CBF. With the advent of non-invasive techniques, study of CBF/CMR in anxiety disorders became easier. A large numbers of research reports are available on the effects of stress, anxiety and panic on CBF/CMR in normals and anxiety disorder patients. This article reviews the available human research on this topic. PMID:21743685

  8. [Magnesium disorder in metabolic bone diseases].

    PubMed

    Ishii, Akira; Imanishi, Yasuo

    2012-08-01

    Magnesium is abundantly distributed among the body. The half of the magnesium exists in the bone. In addition, magnesium is the second most abundant intracellular cation in vertebrates and essential for maintaining physiological function of the cells. Epidemiologic studies have demonstrated that magnesium deficiency is a risk factor for osteoporosis. The mechanism of bone fragility caused by magnesium deficiency has been intensely studied using animal models of magnesium deficiency. Magnesium deficiency causes decreased osteoblastic function and increased number of osteoclasts. Magnesium deficiency also accelerates mineralization in bone. These observations suggest that disturbed bone metabolic turnover and mineralization causes bone fragility.

  9. Disorders of creatine transport and metabolism.

    PubMed

    Longo, Nicola; Ardon, Orly; Vanzo, Rena; Schwartz, Elizabeth; Pasquali, Marzia

    2011-02-15

    Creatine is a nitrogen containing compound that serves as an energy shuttle between the mitochondrial sites of ATP production and the cytosol where ATP is utilized. There are two known disorders of creatine synthesis (both transmitted as autosomal recessive traits: arginine: glycine amidinotransferase (AGAT) deficiency; OMIM 602360; and guanidinoacetate methyltransferase (GAMT) deficiency (OMIM 601240)) and one disorder of creatine transport (X-linked recessive SLC6A8 creatine transporter deficiency (OMIM 300036)). All these disorders are characterized by brain creatine deficiency, detectable by magnetic resonance spectroscopy. Affected patients can have mental retardation, hypotonia, autism or behavioral problems and seizures. The diagnosis of these conditions relies on the measurement of plasma and urine creatine and guanidinoacetate. Creatine levels in plasma are reduced in both creatine synthesis defects and guanidinoacetate is increased in GAMT deficiency. The urine creatine/creatinine ratio is elevated in creatine transporter deficiency with normal plasma levels of creatine and guanidinoacetate. The diagnosis is confirmed in all cases by DNA testing or functional studies. Defects of creatine biosynthesis are treated with creatine supplements and, in GAMT deficiency, with ornithine and dietary restriction of arginine through limitation of protein intake. No causal therapy is yet available for creatine transporter deficiency and supplementation with the guanidinoacetate precursors arginine and glycine is being explored. The excellent response to therapy of early identified patients with GAMT or AGAT deficiency candidates these condition for inclusion in newborn screening programs. Copyright © 2011 Wiley-Liss, Inc.

  10. Shift work and its association with metabolic disorders.

    PubMed

    Brum, Maria Carlota Borba; Filho, Fábio Fernandes Dantas; Schnorr, Claudia Carolina; Bottega, Gustavo Borchardt; Rodrigues, Ticiana C

    2015-01-01

    Although the health burden of shift work has not been extensively studied, evidence suggests that it may affect the metabolic balance and cause obesity and other metabolic disorders. Sleep deprivation, circadian desynchronization and behavioral changes in diet and physical activity are among the most commonly mentioned factors in studies of the association between night work and metabolic disorders. Individual adaptation to night work depends greatly on personal factors such as family and social life, but occupational interventions may also make a positive contribution to the transition to shift work, such as exposure to bright lights during the night shift, melatonin use, shift regularity and clockwise rotation, and dietary adaptations for the metabolic needs of night workers. The evaluation of the impact of night work on health and of the mechanisms underlying this relationship can serve as a basis for intervention strategies to minimize the health burden of shift work. This review aimed to identify highlights regarding therapeutic implications following the association between night and shift work and metabolic disorders, as well as the mechanisms and pathways responsible for these relationships.

  11. Visual and Verbal Learning in a Genetic Metabolic Disorder

    ERIC Educational Resources Information Center

    Spilkin, Amy M.; Ballantyne, Angela O.; Trauner, Doris A.

    2009-01-01

    Visual and verbal learning in a genetic metabolic disorder (cystinosis) were examined in the following three studies. The goal of Study I was to provide a normative database and establish the reliability and validity of a new test of visual learning and memory (Visual Learning and Memory Test; VLMT) that was modeled after a widely used test of…

  12. PHENYLKETONURIA, AN INHERITED METABOLIC DISORDER ASSOCIATED WITH MENTAL RETARDATION.

    ERIC Educational Resources Information Center

    CENTERWALL, WILLARD R.; CENTERWALL, SIEGRIED A.

    ADDRESSED TO PUBLIC HEALTH WORKERS AND PHYSICIANS IN GENERAL PRACTICE, THE PAMPHLET INTRODUCES METHODS OF DETECTING AND MANAGING PHENYLKETONURIA, AN INHERITED METABOLIC DISORDER ASSOCIATED WITH MENTAL RETARDATION. INFORMATION, UPDATED FROM THE 1961 EDITION, IS INCLUDED ON THE INCIDENCE AND GENETICS, BIOCHEMISTRY, AND CLINICAL COURSE OF THE…

  13. Metabolic Syndrome in Children with and without Developmental Coordination Disorder

    ERIC Educational Resources Information Center

    Wahi, Gita; LeBlanc, Paul J.; Hay, John A.; Faught, Brent E.; O'Leary, Debra; Cairney, John

    2011-01-01

    Children with developmental coordination disorder (DCD) have higher rates of obesity compared to children with typical motor development, and, as a result may be at increased risk for developing metabolic syndrome (MetS). The purpose of this study was to determine the presence of MetS and its components among children with and without DCD. This…

  14. Interrelationship between Periapical Lesion and Systemic Metabolic Disorders

    PubMed Central

    Sasaki, Hajime; Hirai, Kimito; Martins, Christine Men; Furusho, Hisako; Battaglino, Ricardo; Hashimoto, Koshi

    2016-01-01

    Periapical periodontitis, also known as periapical lesion, is a common dental disease, along with periodontitis (gum disease). Periapical periodontitis is a chronic inflammatory disease, caused by endodontic infection, and its development is regulated by the host immune/inflammatory response. Metabolic disorders, which are largely dependent on life style such as eating habits, have been interpreted as a “metabolically-triggered” low-grade systemic inflammation and may interact with periapical periodontitis by triggering immune modulation. The host immune system is therefore considered the common fundamental mechanism of both disease conditions. An elevated inflammatory state caused by metabolic disorders can impact the clinical outcome of periapical lesions and interfere with wound healing after endodontic treatment. Although additional well-designed clinical studies are needed, periapical lesions appear to affect insulin sensitivity and exacerbate non-alcoholic steatohepatitis. Immune regulatory cytokines produced by various cell types, including immune cells and adipose tissue, play an important role in this interrelationship. PMID:26881444

  15. The effect of exogenous calcium on mitochondria, respiratory metabolism enzymes and ion transport in cucumber roots under hypoxia.

    PubMed

    He, Lizhong; Li, Bin; Lu, Xiaomin; Yuan, Lingyun; Yang, Yanjuan; Yuan, Yinghui; Du, Jing; Guo, Shirong

    2015-08-25

    Hypoxia induces plant stress, particularly in cucumber plants under hydroponic culture. In plants, calcium is involved in stress signal transmission and growth. The ultimate goal of this study was to shed light on the mechanisms underlying the effects of exogenous calcium on the mitochondrial antioxidant system, the activity of respiratory metabolism enzymes, and ion transport in cucumber (Cucumis sativus L. cv. Jinchun No. 2) roots under hypoxic conditions. Our experiments revealed that exogenous calcium reduces the level of reactive oxygen species (ROS) and increases the activity of antioxidant enzymes in mitochondria under hypoxia. Exogenous calcium also enhances the accumulation of enzymes involved in glycolysis and the tricarboxylic acid (TCA) cycle. We utilized fluorescence and ultrastructural cytochemistry methods to observe that exogenous calcium increases the concentrations of Ca(2+) and K(+) in root cells by increasing the activity of plasma membrane (PM) H(+)-ATPase and tonoplast H(+)-ATPase and H(+)-PPase. Overall, our results suggest that hypoxic stress has an immediate and substantial effect on roots. Exogenous calcium improves metabolism and ion transport in cucumber roots, thereby increasing hypoxia tolerance in cucumber.

  16. The effect of exogenous calcium on mitochondria, respiratory metabolism enzymes and ion transport in cucumber roots under hypoxia

    PubMed Central

    He, Lizhong; Li, Bin; Lu, Xiaomin; Yuan, Lingyun; Yang, Yanjuan; Yuan, Yinghui; Du, Jing; Guo, Shirong

    2015-01-01

    Hypoxia induces plant stress, particularly in cucumber plants under hydroponic culture. In plants, calcium is involved in stress signal transmission and growth. The ultimate goal of this study was to shed light on the mechanisms underlying the effects of exogenous calcium on the mitochondrial antioxidant system, the activity of respiratory metabolism enzymes, and ion transport in cucumber (Cucumis sativus L. cv. Jinchun No. 2) roots under hypoxic conditions. Our experiments revealed that exogenous calcium reduces the level of reactive oxygen species (ROS) and increases the activity of antioxidant enzymes in mitochondria under hypoxia. Exogenous calcium also enhances the accumulation of enzymes involved in glycolysis and the tricarboxylic acid (TCA) cycle. We utilized fluorescence and ultrastructural cytochemistry methods to observe that exogenous calcium increases the concentrations of Ca2+ and K+ in root cells by increasing the activity of plasma membrane (PM) H+-ATPase and tonoplast H+-ATPase and H+-PPase. Overall, our results suggest that hypoxic stress has an immediate and substantial effect on roots. Exogenous calcium improves metabolism and ion transport in cucumber roots, thereby increasing hypoxia tolerance in cucumber. PMID:26304855

  17. Inherited Variation in Cytokine, Acute Phase Response, and Calcium Metabolism Genes Affects Susceptibility to Infective Endocarditis

    PubMed Central

    Rutkovskaya, Natalia V.; Kondyukova, Natalia V.; Odarenko, Yuri N.; Kazachek, Yana V.; Tsepokina, Anna V.; Barbarash, Leonid S.

    2017-01-01

    Infective endocarditis (IE) is a septic inflammation of the endocardium. Recognition of microbial patterns, cytokine and acute phase responses, hemostasis features, and alterations in plasma lipid and calcium profile all have been reported to affect pathogenesis and clinical course of IE. Having recruited 123 patients with IE and 300 age-, sex-, and ethnicity-matched healthy blood donors, we profiled their genomic DNA for 35 functionally significant polymorphisms within the 22 selected genes involved in the abovementioned pathways, with the further genetic association analysis. We found that the G/A genotype of the rs1143634 polymorphism within the IL1B gene, the G/T genotype of the rs3212227 polymorphism within the IL12B gene, the A/G genotype of the rs1130864 polymorphism within the CRP gene, and the G allele of the rs1801197 polymorphism within the CALCR gene were associated with a decreased risk of IE whereas the T/T genotype of the rs1205 polymorphism within the CRP gene was associated with a higher risk of IE. Furthermore, heterozygous genotypes of the rs1143634 and rs3212227 polymorphisms were associated with the higher plasma levels of IL-1β and IL-12, respectively. Our results indicate that inherited variation in the cytokine, acute phase response, and calcium metabolism pathways may be linked to IE. PMID:28659664

  18. Substrate kinetics in patients with disorders of skeletal muscle metabolism.

    PubMed

    Ørngreen, Mette Cathrine

    2016-07-01

    The main purpose of the following studies was to investigate pathophysiological mechanisms in fat and carbohydrate metabolism and effect of nutritional interventions in patients with metabolic myopathies and in patients with severe muscle wasting. Yet there is no cure for patients with skeletal muscle disorders. The group of patients is heterozygous and this thesis is focused on patients with metabolic myopathies and low muscle mass due to severe muscle wasting. Disorders of fatty acid oxidation (FAO) are, along with myophosphorylase deficiency (McArdle disease), the most common inborn errors of metabolism leading to recurrent episodes of rhabdomyolysis in adults. Prolonged exercise, fasting, and fever are the main triggering factors for rhabdomyolysis in these conditions, and can be complicated by acute renal failure. Patients with low muscle mass are in risk of loosing their functional skills and depend on a wheel chair and respiratory support. We used nutritional interventions and metabolic studies with stable isotope technique and indirect calorimetry in patients with metabolic myopathies and patients with low muscle mass to get information of the metabolism of the investigated diseases, and to gain knowledge of the biochemical pathways of intermediary metabolism in human skeletal muscle. We have shown that patients with fat metabolism disorders in skeletal muscle affecting the transporting enzyme of fat into the mitochondria (carnitine palmitoyltransferase II deficiency) and affecting the enzyme responsible for breakdown of the long-chain fatty acids (very long chain acyl-CoA dehydrogenase deficiency) have a normal fatty acid oxidation at rest, but enzyme activity is too low to increase fatty acid oxidation during exercise. Furthermore, these patients benefit from a carbohydrate rich diet. Oppositely is exercise capacity worsened by a fat-rich diet in these patients. The patients also benefit from IV glucose, however, when glucose is given orally just before

  19. Minireview: The Intimate Link Between Calcium Sensing Receptor Trafficking and Signaling: Implications for Disorders of Calcium Homeostasis

    PubMed Central

    2012-01-01

    The calcium-sensing receptor (CaSR) regulates organismal Ca2+ homeostasis. Dysregulation of CaSR expression or mutations in the CASR gene cause disorders of Ca2+ homeostasis and contribute to the progression or severity of cancers and cardiovascular disease. This brief review highlights recent findings that define the CaSR life cycle, which controls the cellular abundance of CaSR and CaSR signaling. A novel mechanism, termed agonist-driven insertional signaling (ADIS), contributes to the unique hallmarks of CaSR signaling, including the high degree of cooperativity and the lack of functional desensitization. Agonist-mediated activation of plasma membrane-localized CaSR increases the rate of insertion of CaSR at the plasma membrane without altering the constitutive endocytosis rate, thereby acutely increasing the maximum signaling response. Prolonged CaSR signaling requires a large intracellular ADIS-mobilizable pool of CaSR, which is maintained by signaling-mediated increases in biosynthesis. This model provides a rational framework for characterizing the defects caused by CaSR mutations and the altered functional expression of wild-type CaSR in disease states. Mechanistic dissection of ADIS of CaSR should lead to optimized pharmacological approaches to normalize CaSR signaling in disorders of Ca2+ homeostasis. PMID:22745192

  20. Bone Mineral Density Changes after Physical Training and Calcium Intake in Students with Attention Deficit and Hyper Activity Disorders

    ERIC Educational Resources Information Center

    Arab ameri, Elahe; Dehkhoda, Mohammad Reza; Hemayattalab, Rasool

    2012-01-01

    In this study we investigate the effects of weight bearing exercise and calcium intake on bone mineral density (BMD) of students with attention deficit and hyper activity (ADHD) disorder. For this reason 54 male students with ADHD (age 8-12 years old) were assigned to four groups with no differences in age, BMD, calcium intake, and physical…

  1. Metabolic and molecular responses to calcium soap of fish oil fed to ewes during peripartal period.

    PubMed

    Sheibani, S; Mohammadi-Sangcheshmeh, A; Alamouti, A A; Khadem, A A; Norouzian, M A

    2017-10-31

    It has been shown that n-3 long chain fatty acids (n-3 LCFA) are involved in energy/lipid metabolisms, reproductive parameters, and molecular regulations leading to maintained homeostasis. We hypothesized that supplementation of peripartal diets with fish oil (FO), as a source of n-3 LCFA, could improve energy balance and modulate metabolic pressure in a sheep model. Prepartum ewes (n = 24) were fed control (CON) or calcium soap of fish oil (FO) supplemented-diet from four weeks before until three weeks after parturation. Feed intake, body weight (BW) change, plasma metabolites, colostrums/milk composition, and fatty acids profile of milk along with the expression of core microRNAs in glucose and lipid metabolism were evaluated. Prepartal feed intake decreased in FO group (1674 ± 33.26 vs. 1812 ± 35.56) though post-partal intake was similar. Differences in BW were not also significant (55.47 ± 2.07 in CON vs. 53.69 ± 1.94 in FO). No differences were observed in plasma metabolites except for cholesterol that was lower in FO group (56.25 ± 0.71 vs. 53.09 ± 0.61). Milk fat percentage was reduced (8.82 ± 0.49 vs. 7.03 ± 0.45) while the percentage of milk total n-3 LCFA increased in FO group. In accordance, the relative transcript abundance of miR-101 (0.215 ± 0.08) and miR-103 (0.37 ± 0.15) decreased by FO supplementation. Results showed that FO supplementation during peripartal period decreased milk fat, feed intake, plasma cholesterol, milk n-6:n-3 ratio and the expression of miR-101. Although the trend indicated that FO could alter lipid metabolism during transition period, further studies are needed to fully address its effect on energy balance and homeorhetic processes.

  2. Calcium, magnesium, and phosphorus metabolism, and parathyroid-calcitonin function during prolonged exposure to elevated CO2 concentrations on submarines.

    PubMed

    Messier, A A; Heyder, E; Braithwaite, W R; McCluggage, C; Peck, A; Schaefer, K E

    1979-01-01

    Studies of calcium and phosphorus metabolism and acid-base balance were carried out on three Fleet Ballistic Missile (FBM) submarines during prolonged exposure to elevated concentrations of CO2. The average CO2 concentration in the submarine atmosphere during patrols ranged from 0.85% to 1% CO2. In the three studies, in which 9--15 subjects participated, the urinary excretion of calcium and phosphate fell during the first three weeks to a level commensurate with a decrease in plasma calcium and increase in phosphorus. In the fourth week of one patrol, a marked increase was found in urinary calcium excretion, associated with a rise in blood PCO2 and bicarbonate. Urinary calcium excretion decreased again during the 5th to 8th week, with a secondary decrease in blood pH and plasma calcium. During the third patrol, the time course of acid-base changes corresponded well with that found during the second patrol. There was a trend toward an increase in plasma calcium between the fourth and fifth week commensurate with the transient rise in pH and bicarbonate. Plasma parathyroid and calcitonin hormone activities were measured in two patrols and no significant changes were found. Hydroxyproline excretion decreased in the three-week study and remained unchanged in the second patrol, which lasted 57 days. It is suggested that during prolonged exposure to low levels of CO2 (up to 1% CO2), calcium metabolism is controlled by the uptake and release of CO2 in the bones. The resulting phases in bone buffering, rather than renal regulation, determine acid-base balance.

  3. Disorders of lipid metabolism in muscle.

    PubMed

    Di Mauro, S; Trevisan, C; Hays, A

    1980-01-01

    At rest and during sustained exercise, lipids are the main source of energy for muscle. Free fatty acids become available to muscle from plasma free fatty acids and triglycerides, and from intracellular triglycride lipid droplets. Transport of long-chain fatty acyl groups into the mitochondria requires esterification and de-esterification with carnitine by the "twin" enzymes carnitine palmityltransferase (CPT) I and II, bound to the outer and inner faces of the inner mitochondrial membrane. Carnitine deficiency occurs in two clinical syndromes. (1) In the myopathic form, there is weakness; muscle biopsy shows excessive accumulation of lipid droplets; and the carnitine concentration is markedly decreased in muscle but normal in plasma. (2) In the systemic form, there are weakness and recurrent episodes of hepatic encephalopathy; muscle biopsy shows lipid storage; and the carnitine concentration is decreased in muscle, liver, and plasma. The etiology of carnitine deficiency is not known in either the myopathic or the systemic form, but administration of carnitine or corticosteroids has been beneficial in some patients. "Secondary" carnitine deficiency may occur in patients with malnutrition, liver disease, chronic hemodialysis, and, possibly, mitochondrial disorders. CPT deficiency causes recurrent myoglobinuria, usually precipitated by prolonged exercise or fasting. Muscle biopsy may be normal or show varying degrees of lipid storage. Genetic transmission is probably autosomal recessive, but the great male predominance (20/21) remains unexplained. In many cases, lipid storage myopathy is not accompanied by carnitine or CPT deficiency, and the biochemical error remains to be identified.

  4. Calcium supplementation during pregnancy for preventing hypertensive disorders and related problems.

    PubMed

    Hofmeyr, G Justus; Lawrie, Theresa A; Atallah, Alvaro N; Duley, Lelia; Torloni, Maria R

    2014-06-24

    Pre-eclampsia and eclampsia are common causes of serious morbidity and death. Calcium supplementation may reduce the risk of pre-eclampsia, and may help to prevent preterm birth. To assess the effects of calcium supplementation during pregnancy on hypertensive disorders of pregnancy and related maternal and child outcomes. We searched the Cochrane Pregnancy and Childbirth Group's Trials Register (28 March 2013) and contacted study authors for more data where possible. We updated the search in May 2014 and added the results to the 'Awaiting Classification' section of the review. Randomised controlled trials (RCTs) comparing high-dose (at least 1 g daily of calcium) or low-dose calcium supplementation during pregnancy with placebo or no calcium. We assessed eligibility and trial quality, extracted and double-entered data. High-dose calcium supplementation (≥1 g/day)We included 14 studies in the review, however one study contributed no data. We included 13 high-quality studies in our meta-analyses (15,730 women). The average risk of high blood pressure (BP) was reduced with calcium supplementation compared with placebo (12 trials, 15,470 women: risk ratio (RR) 0.65, 95% confidence interval (CI) 0.53 to 0.81; I² = 74%). There was also a significant reduction in the risk of pre-eclampsia associated with calcium supplementation (13 trials, 15,730 women: RR 0.45, 95% CI 0.31 to 0.65; I² = 70%). The effect was greatest for women with low calcium diets (eight trials, 10,678 women: average RR 0.36, 95% CI 0.20 to 0.65; I² = 76%) and women at high risk of pre-eclampsia (five trials, 587 women: average RR 0.22, 95% CI 0.12 to 0.42; I² = 0%). These data should be interpreted with caution because of the possibility of small-study effect or publication bias.The composite outcome maternal death or serious morbidity was reduced (four trials, 9732 women; RR 0.80, 95% CI 0.65 to 0.97; I² = 0%). Maternal deaths were not significantly different (one trial of 8312 women: calcium

  5. Effect of metabolic and respiratory acidosis on intracellular calcium in osteoblasts

    PubMed Central

    Bushinsky, David A.

    2010-01-01

    In vivo, metabolic acidosis {decreased pH from decreased bicarbonate concentration ([HCO3−])} increases urine calcium (Ca) without increased intestinal Ca absorption, resulting in a loss of bone Ca. Conversely, respiratory acidosis [decreased pH from increased partial pressure of carbon dioxide (Pco2)] does not appreciably alter Ca homeostasis. In cultured bone, chronic metabolic acidosis (Met) significantly increases cell-mediated net Ca efflux while isohydric respiratory acidosis (Resp) does not. The proton receptor, OGR1, appears critical for cell-mediated, metabolic acid-induced bone resorption. Perfusion of primary bone cells or OGR1-transfected Chinese hamster ovary (CHO) cells with Met induces transient peaks of intracellular Ca (Cai). To determine whether Resp increases Cai, as does Met, we imaged Cai in primary cultures of bone cells. pH for Met = 7.07 ([HCO3−] = 11.8 mM) and for Resp = 7.13 (Pco2 = 88.4 mmHg) were similar and lower than neutral (7.41). Both Met and Resp induced a marked, transient increase in Cai in individual bone cells; however, Met stimulated Cai to a greater extent than Resp. We used OGR1-transfected CHO cells to determine whether OGR1 was responsible for the greater increase in Cai in Met than Resp. Both Met and Resp induced a marked, transient increase in Cai in OGR1-transfected CHO cells; however, in these cells Met was not different than Resp. Thus, the greater induction of Cai by Met in primary bone cells is not a function of OGR1 alone, but must involve H+ receptors other than OGR1, or pathways sensitive to Pco2, HCO3−, or total CO2 that modify the effect of H+ in primary bone cells. PMID:20504884

  6. Effect of metabolic and respiratory acidosis on intracellular calcium in osteoblasts.

    PubMed

    Frick, Kevin K; Bushinsky, David A

    2010-08-01

    In vivo, metabolic acidosis {decreased pH from decreased bicarbonate concentration ([HCO(3)(-)])} increases urine calcium (Ca) without increased intestinal Ca absorption, resulting in a loss of bone Ca. Conversely, respiratory acidosis [decreased pH from increased partial pressure of carbon dioxide (Pco(2))] does not appreciably alter Ca homeostasis. In cultured bone, chronic metabolic acidosis (Met) significantly increases cell-mediated net Ca efflux while isohydric respiratory acidosis (Resp) does not. The proton receptor, OGR1, appears critical for cell-mediated, metabolic acid-induced bone resorption. Perfusion of primary bone cells or OGR1-transfected Chinese hamster ovary (CHO) cells with Met induces transient peaks of intracellular Ca (Ca(i)). To determine whether Resp increases Ca(i), as does Met, we imaged Ca(i) in primary cultures of bone cells. pH for Met = 7.07 ([HCO(3)(-)] = 11.8 mM) and for Resp = 7.13 (Pco(2) = 88.4 mmHg) were similar and lower than neutral (7.41). Both Met and Resp induced a marked, transient increase in Ca(i) in individual bone cells; however, Met stimulated Ca(i) to a greater extent than Resp. We used OGR1-transfected CHO cells to determine whether OGR1 was responsible for the greater increase in Ca(i) in Met than Resp. Both Met and Resp induced a marked, transient increase in Ca(i) in OGR1-transfected CHO cells; however, in these cells Met was not different than Resp. Thus, the greater induction of Ca(i) by Met in primary bone cells is not a function of OGR1 alone, but must involve H(+) receptors other than OGR1, or pathways sensitive to Pco(2), HCO(3)(-), or total CO(2) that modify the effect of H(+) in primary bone cells.

  7. Metabolic and skeletal effects of low and high doses of calcium acetate in patients with preterminal chronic renal failure.

    PubMed

    Phelps, Kenneth R; Stern, Marc; Slingerland, Alice; Heravi, Mahin; Strogatz, David S; Haqqie, Syed S

    2002-01-01

    Secondary hyperparathyroidism commonly evolves, as the glomerular filtration rate falls. The metabolic and skeletal effects of a possible remedy, calcium acetate, have not been studied in patients with preterminal chronic renal failure. Men with a mean creatinine clearance of approximately 30 ml/min took calcium acetate for 24 weeks at doses which provided 507 or 1,521 mg calcium/day with meals. Metabolic determinations were made at intervals of 4-8 weeks, and the bone mineral density (BMD) was measured at the beginning and at the end of the trial. The low-dose regimen produced no metabolic or skeletal effect. In subjects prescribed the high-dose regimen, the 24-hour urine phosphorus excretion fell from 0.53 mg/mg creatinine to values ranging from 0.34 to 0.41 mg/mg creatinine. The theoretical phosphorus threshold concentration rose by a maximum of 38.6%, and the serum phosphorus concentration did not change. The mean serum calcium concentration rose by a maximum of 7.2%. The mean fractional changes in parathyroid hormone and 1,25-dihydroxyvitamin D concentrations ranged from -27.0 to -39.6% and from -5.0 to -20.3%, respectively. The BMD increased at L1, L3, and L4. Calcium acetate prescribed to deliver 1,521 mg calcium/day with meals reduced parathyroid hormone and 1,25-dihydroxyvitamin D concentrations and increased lumbar BMD in men with preterminal chronic renal failure. Copyright 2002 S. Karger AG, Basel

  8. Effect of excess dietary salt on calcium metabolism and bone mineral in a spaceflight rat model

    NASA Technical Reports Server (NTRS)

    Navidi, Meena; Wolinsky, Ira; Fung, Paul; Arnaud, Sara B.

    1995-01-01

    High levels of salt promote urinary calcium (UCa) loss and have the potential to cause bone mineral deficits if intestinal Ca absorption does not compensate for these losses. To determine the effect of excess dietary salt on the osteopenia that follows skeletal unloading, we used a spaceflight model that unloads the hindlimbs of 200-g rats by tail suspension (S). Rats were studied for 2 wk on diets containing high salt (4 and 8%) and normal calcium (0.45%) and for 4 wk on diets containing 8% salt (HiNa) and 0.2% Ca (LoCa). Final body weights were 9-11% lower in S than in control rats (C) in both experiments, reflecting lower growth rates in S than in C during pair feeding. UCa represented 12% of dietary Ca on HiNA diets and was twofold higher in S than in C transiently during unloading. Net intestinal Ca absorption was consistently 11-18% lower in S than in C. Serum 1,25-dihydroxyvitamin D was unaffected by either LoCa or HiNa diets in S but was increased by LoCa and HiNa diets in C. Despite depressed intestinal Ca absoption in S and a sluggish response of the Ca endocrine system to HiNa diets, UCa loss did not appear to affect the osteopenia induced by unloading. Although any deficit in bone mineral content from HiNa diets may have been too small to detect or the duration of the study too short to manifest, there were clear differences in Ca metabolism from control levels in the response of the spaceflight model to HiNa diets, indicated by depression of intestinal Ca absorption and its regulatory hormone.

  9. Effects of dietary supplementation of arginine-silicate-inositol complex on absorption and metabolism of calcium of laying hens

    PubMed Central

    Orhan, Cemal; Tuzcu, Mehmet; Hayirli, Armagan; Komorowski, James R.; Sahin, Nurhan

    2018-01-01

    The effects of supplementation of arginine-silicate-inositol complex (ASI; 49.5–8.2–25 g/kg, respectively) to laying hens were investigated with respect to eggshell quality, calcium (Ca) balance, and expression of duodenal proteins related to Ca metabolism (calbindin and tight junction proteins). A total of 360 laying hens, 25 weeks old, were divided into 3 groups consisting of 6 replicate of cages, 20 birds per cage. The groups were fed a basal diet and the basal diet supplemented with 500 or 1000 mg ASI complex per kilogram for 90 days. Data were analyzed by ANCOVA using data during the first week of the adaptation period as covariates. As the ASI complex supplementation level increased, there were increases in feed intake (P < 0.0001), egg production (P < 0.001), egg weight (P < 0.0001) and eggshell weight (P < 0.001) weight, and shell thickness (P < 0.001) and decreases in feed conversion ratio and cracked egg percentage (P < 0.0001 for both). Concentrations of serum osteocalcin (P < 0.0001), vitamin D (P < 0.0001), calcium (P < 0.001), phosphorus (P < 0.001), and alkaline phosphatase (P < 0.008) as well as amounts of calcium retention (P < 0.0001) and eggshell calcium deposition (P < 0.001), and Ca balance (P < 0.0001) increased, whereas amount of calcium excretion (P < 0.001) decreased linearly in a dose-dependent manner. The ASI complex supplementation increased expressions of calcium transporters (calbindin-D28k, N sodium-calcium exchanger, plasma membrane calcium ATPase, and vitamin D receptor) and tight junction proteins (zonula occludens-1 and occludin) in the duodenum in a linear fashion (P < 0.0001 for all). In conclusion, provision of dietary ASI complex to laying hens during the peak laying period improved eggshell quality through improving calcium utilization as reflected by upregulation of genes related to the calcium metabolism. Further studies are needed to elucidate the contribution of each of the ASI complex ingredients. PMID:29360830

  10. Geraniol improves the impaired vascular reactivity in diabetes and metabolic syndrome through calcium channel blocking effect.

    PubMed

    El-Bassossy, Hany M; Elberry, Ahmed A; Ghareib, Salah A

    2016-08-01

    The aim of the present study is to investigate the effect and possible mechanism of action of geraniol on the impaired vascular reactivity of aortic rings isolated from diabetes or metabolic syndrome (MS) -induced rats. Male Wistar rats were divided into control, type 1 diabetes and metabolic syndrome (MS) groups. Diabetes was induced by a single intraperitoneal injection of streptozotocin (50mg/kg) and left for 10weeks to develop vascular complications. MS was induced by adding 10% fructose and 3% salt to water and diet for 12weeks. The present study investigated the effect of in vitro incubation with geraniol (10-300μM) on the vasoconstrictor response to phenylephrine (PE) and the vasodilator response to acetylcholine (ACh) as well as its effect on aortae incubated with methylglyoxal (MG) as an advanced glycation end product (AGE). To investigate the mechanism of action of geraniol, different blockers are used, including Nω-nitro-L-arginine methyl ester hydrochloride (L-NAME, 100μM), tetraethylammonium chloride (TEA, 10mM), and indomethacin (INDO, 5μM). Moreover, the effect of calcium chloride (CaCl2) on aortic rings precontracted with PE or potassium chloride (KCl) was examined. Thirty minutes incubation with geraniol alleviated the exaggerated vasoconstriction in aortae isolated from diabetic or MS animals or in vitro exposed to MG in a concentration-dependent manner. In addition, geraniol improved the vasodilatation response of diabetic or MS aortae or aortae exposed to MG. In search for the mechanism; geraniol produced concentration-dependent relaxation of both PE and KCl-precontracted aorta. Geraniol relaxation was not affected by L-NAME, INDO or TEA. However, geraniol significantly inhibited voltage dependent and receptor mediated Ca(2+)-induced contraction activated by KCl or PE respectively. In conclusion, geraniol ameliorates impaired vascular reactivity in experimentally induced diabetes and MS. The effect may be partially attributed to an

  11. The metabolic syndrome, diabetes, and subclinical atherosclerosis assessed by coronary calcium.

    PubMed

    Wong, Nathan D; Sciammarella, Maria G; Polk, Donna; Gallagher, Amy; Miranda-Peats, Lisa; Whitcomb, Brian; Hachamovitch, Rory; Friedman, John D; Hayes, Sean; Berman, Daniel S

    2003-05-07

    We compared the prevalence and extent of coronary artery calcium (CAC) among persons with the metabolic syndrome (MetS), diabetes, and neither condition. The prevalence and extent of CAC has not been compared among those with MetS, diabetes, or neither condition. Of 1,823 persons (36% female) age 20 to 79 years who had screening for CAC by computed tomography, 279 had MetS, 150 had diabetes, and the remainder (n = 1,394) had neither condition. Metabolic syndrome was defined with >or=3 of the following: body mass index >or=30 kg/m(2); high-density lipoprotein cholesterol <40 mg/dl if male or <50 mg/dl if female; triglycerides >or=150 mg/dl; blood pressure >or=130/85 mm Hg or on treatment; or fasting glucose 110 to 125 mg/dl. The prevalence and odds of any and significant (>or=75th percentile) CAC among these groups and by number of MetS risk factors were determined. Those with neither MetS nor diabetes, MetS, or diabetes had a prevalence of CAC of 53.5%, 58.8%, and 75.3% (p < 0.001), respectively, among men and 37.6%, 50.8%, and 52.6% (p < 0.001), respectively, among women. Coronary artery calcium increased by the number (0 to 5) of MetS risk factors (from 34.0% to 58.3%) (p < 0.001). Forty-one percent of subjects with MetS had either a >20% 10-year risk of CHD or CAC >or=75th percentile for age and gender. Risk factor-adjusted odds for the presence of CAC were 1.40 (95% confidence interval [CI] 1.05 to 1.87) among those with MetS and 1.67 (95% CI 1.12 to 2.50) among those with diabetes, versus those with neither condition. Those with MetS or diabetes have an increased likelihood of CAC compared with those having neither condition.

  12. Interactions of Mitochondria/Metabolism and Calcium Regulation in Alzheimer's Disease: A Calcinist Point of View.

    PubMed

    Gibson, Gary E; Thakkar, Ankita

    2017-06-01

    Decades of research suggest that alterations in calcium are central to the pathophysiology of Alzheimer's Disease (AD). Highly reproducible changes in calcium dynamics occur in cells from patients with both genetic and non-genetic forms of AD relative to controls. The most robust change is an exaggerated release of calcium from internal stores. Detailed analysis of these changes in animal and cell models of the AD-causing presenilin mutations reveal robust changes in ryanodine receptors, inositol tris-phosphate receptors, calcium leak channels and store activated calcium entry. Similar anomalies in calcium result when AD-like changes in mitochondrial enzymes or oxidative stress are induced experimentally. The calcium abnormalities can be directly linked to the altered tau phosphorylation, amyloid precursor protein processing and synaptic dysfunction that are defining features of AD. A better understanding of these changes is required before using calcium abnormalities as therapeutic targets.

  13. [How to manage mineral metabolism disorders in renal failure].

    PubMed

    Jean, Guillaume

    2011-11-01

    Mineral metabolism abnormalities are frequently observed in patients with chronic kidney disease (CKD). The bone and cardiovascular consequences should lead to the implementation of some adapted strategies for the prevention and treatment on the basis of the physiopathology of the disease and international recommendations. Biological bone markers such as serum parathyroid hormone (PTH) and alkaline phosphatase (ALP) are necessary to classify bone diseases without the need for bone biopsy. Elevated levels of bone markers are detected in cases of secondary hyperparathyroidism (SHPT), whereas decreased levels are observed in cases of adynamic bone disease (ABD). Bone mineral density, however, is not useful for the diagnosis. Vitamin D supplementation and reducing hyperphosphataemia by dietary phosphate-intake restriction, phosphate binders, and dialysis, are the main steps for the prevention of SHPT. Calcitriol analogs and calcimimetics should be used in second line in cases of SHPT. For the treatment of ABD, excess use of calcium salts and calcitriol analogs need to be avoided. Managing these therapies adequately can help maintain the main biological values (i.e. serum PTH, calcium, phosphorus, and ALP) within their recommended ranges. Copyright © 2011 Elsevier Masson SAS. All rights reserved.

  14. Increased Expression of Fatty-Acid and Calcium Metabolism Genes in Failing Human Heart

    PubMed Central

    Rodríguez-Penas, Diego; Feijóo-Bandín, Sandra; Noguera-Moreno, Teresa; Calaza, Manuel; Álvarez-Barredo, María; Mosquera-Leal, Ana; Parrington, John; Brugada, Josep; Portolés, Manuel; Rivera, Miguel; González-Juanatey, José Ramón; Lago, Francisca

    2012-01-01

    Background Heart failure (HF) involves alterations in metabolism, but little is known about cardiomyopathy-(CM)-specific or diabetes-independent alterations in gene expression of proteins involved in fatty-acid (FA) uptake and oxidation or in calcium-(Ca2+)-handling in the human heart. Methods RT-qPCR was used to quantify mRNA expression and immunoblotting to confirm protein expression in left-ventricular myocardium from patients with HF (n = 36) without diabetes mellitus of ischaemic (ICM, n = 16) or dilated (DCM, n = 20) cardiomyopathy aetiology, and non-diseased donors (CTL, n = 6). Results Significant increases in mRNA of genes regulating FA uptake (CD36) and intracellular transport (Heart-FA-Binding Protein (HFABP)) were observed in HF patients vs CTL. Significance was maintained in DCM and confirmed at protein level, but not in ICM. mRNA was higher in DCM than ICM for peroxisome-proliferator-activated-receptor-alpha (PPARA), PPAR-gamma coactivator-1-alpha (PGC1A) and CD36, and confirmed at the protein level for PPARA and CD36. Transcript and protein expression of Ca2+-handling genes (Two-Pore-Channel 1 (TPCN1), Two-Pore-Channel 2 (TPCN2), and Inositol 1,4,5-triphosphate Receptor type-1 (IP3R1)) increased in HF patients relative to CTL. Increases remained significant for TPCN2 in all groups but for TPCN1 only in DCM. There were correlations between FA metabolism and Ca2+-handling genes expression. In ICM there were six correlations, all distinct from those found in CTL. In DCM there were also six (all also different from those found in CTL): three were common to and three distinct from ICM. Conclusion DCM-specific increases were found in expression of several genes that regulate FA metabolism, which might help in the design of aetiology-specific metabolic therapies in HF. Ca2+-handling genes TPCN1 and TPCN2 also showed increased expression in HF, while HF- and CM-specific positive correlations were found among several FA and Ca2+-handling genes

  15. Effects of Astragalus membranaceus with supplemental calcium on bone mineral density and bone metabolism in calcium-deficient ovariectomized rats.

    PubMed

    Kang, Se-Chan; Kim, Hee Jung; Kim, Mi-Hyun

    2013-01-01

    It has been reported that Astragalus membranaceus, an Asian traditional herb, has an estrogenic effect in vitro. To examine the possible role of A. membranaceus extract with supplemental calcium (Ca) on bone status in calcium-deficient (LCa) ovariectomized (OVX) rats, a total of 48 female rats were divided into six groups: (1) normal control, (2) sham operation with LCa (sham-LCa), (3) OVX with LCa (OVX-LCa), (4) A. membranaceus supplementation with OVX-LCa (OVX-MLCa), (5) Ca supplementation with OVX (OVX-Ca), and (6) A. membranaceus and Ca supplementation with OVX (OVX-MCa). A. membranaceus ethanol extract (500 mg/kg BW) and/or Ca (800 mg/kg BW) were administered orally for 8 weeks along with a Ca-deficient diet. Results revealed that Ca supplementation with or without A. membranaceus extract significantly improved bone mineral density, biomechanical strength, and ash weight of the femur and tibia in OVX rats. High Ca with A. membranaceus combination supplementation significantly increased the ash weight of the femur and tibia and decreased urinary Ca excretion compared with supplementation of Ca alone. Uterine weight was not changed by A. membranaceus administration in OVX rats. These results suggest that A. membranaceus extract combined with supplemental Ca may be more protective against the Ca loss of bone than A. membranaceus or supplementation of Ca alone in calcium-insufficient postmenopausal women.

  16. Adaptations to Climate in Candidate Genes for Common Metabolic Disorders

    PubMed Central

    Hancock, Angela M; Witonsky, David B; Gordon, Adam S; Eshel, Gidon; Pritchard, Jonathan K; Coop, Graham; Di Rienzo, Anna

    2008-01-01

    Evolutionary pressures due to variation in climate play an important role in shaping phenotypic variation among and within species and have been shown to influence variation in phenotypes such as body shape and size among humans. Genes involved in energy metabolism are likely to be central to heat and cold tolerance. To test the hypothesis that climate shaped variation in metabolism genes in humans, we used a bioinformatics approach based on network theory to select 82 candidate genes for common metabolic disorders. We genotyped 873 tag SNPs in these genes in 54 worldwide populations (including the 52 in the Human Genome Diversity Project panel) and found correlations with climate variables using rank correlation analysis and a newly developed method termed Bayesian geographic analysis. In addition, we genotyped 210 carefully matched control SNPs to provide an empirical null distribution for spatial patterns of allele frequency due to population history alone. For nearly all climate variables, we found an excess of genic SNPs in the tail of the distributions of the test statistics compared to the control SNPs, implying that metabolic genes as a group show signals of spatially varying selection. Among our strongest signals were several SNPs (e.g., LEPR R109K, FABP2 A54T) that had previously been associated with phenotypes directly related to cold tolerance. Since variation in climate may be correlated with other aspects of environmental variation, it is possible that some of the signals that we detected reflect selective pressures other than climate. Nevertheless, our results are consistent with the idea that climate has been an important selective pressure acting on candidate genes for common metabolic disorders. PMID:18282109

  17. [Features of metabolic syndrome in patients with depressive disorder].

    PubMed

    Zeman, M; Jirák, R; Zák, A; Jáchymová, M; Vecka, M; Tvrzická, E; Vávrová, L; Kodydková, J; Stanková, B

    2009-01-01

    Depressive disorder is a serious illness with a high incidence, proxime accessit after anxiety disorders among the psychiatric diseases. It is accompanied by an increased risk of development of type 2 diabetes mellitus, cardiovascular disease, and by increased all-cause mortality. Recently published data have suggested that factors connected with the insulin resistance are at the background of this association. In this pilot study we have investigated parameters of lipid metabolism and glucose homeostasis in consecutively admitted patients suffering from depressive disorder (DD) (group of 42 people), in 57 patients with the metabolic syndrome (MetS) and in a control group of 49 apparently healthy persons (CON). Depressive patients did not differ from the control group by age or body mass index (BMI) value, but they had statistically significantly higher concentrations of serum insulin, C-peptide, glucose, triglycerides (TG), conjugated dienes in LDL particles (CD-LDL), higher value of microalbuminuria and of insulin resistance (HOMA-IR) index. They simultaneously had significantly lower value of the insulin sensitivity (QUICKI) index. In comparison with the MetS group the depressive patients were characterized by significantly lower both systolic and diastolic blood pressure, BMI , serum TG, apolipoprotein B, uric acid, C-peptide and by higher concentrations of apolipoprotein A-I and HDL-cholesterol. On the contrary, we have not found statistically significant differences between the DD and MetS groups in the concentrations of serum insulin, glucose, HOMA and QUICKI indices, in CD-LDL and MAU. In this pilot study, we have found in patients with depressive disorder certain features of metabolic syndrome, especially insulin resistance and oxidative stress.

  18. Preliminary validation of assays to measure parameters of calcium metabolism in captive Asian and African elephants in western Europe.

    PubMed

    van Sonsbeek, Gerda R; van der Kolk, Johannes H; van Leeuwen, Johannes P T M; Schaftenaar, Willem

    2011-05-01

    Hypocalcemia is a well known cause of dystocia in animals, including elephants in captivity. In order to study calcium metabolism in elephants, it is of utmost importance to use properly validated assays, as these might be prone to specific matrix effects in elephant blood. The aim of the current study was to conduct preliminary work for validation of various parameters involved in calcium metabolism in both blood and urine of captive elephants. Basal values of these parameters were compared between Asian elephants (Elephas maximus) and African elephants (Loxodonta africana). Preliminary testing of total calcium, inorganic phosphorus, and creatinine appeared valid for use in plasma and creatinine in urine in both species. Furthermore, measurements of bone alkaline phosphatase and N-terminal telopeptide of type I collagen appeared valid for use in Asian elephants. Mean heparinized plasma ionized calcium concentration and pH were not significantly affected by 3 cycles of freezing and thawing. Storage at 4 °C, room temperature, and 37 °C for 6, 12, and 24 hr did not alter the heparinized plasma ionized calcium concentration in Asian elephants. The following linear regression equation using pH (range: 6.858-7.887) and ionized calcium concentration in heparinized plasma was utilized: iCa(7.4) (mmol/l) = -2.1075 + 0.3130·pH(actual) + 0.8296·iCa(actual) (mmol/l). Mean basal values for pH and plasma in Asian elephant whole blood were 7.40 ± 0.048 and 7.49 ± 0.077, respectively. The urinary specific gravity and creatinine concentrations in both Asian and African elephants were significantly correlated and both were significantly lower in Asian elephants. © 2011 The Author(s)

  19. Calcium Homeostasis and Muscle Energy Metabolism Are Modified in HspB1-Null Mice.

    PubMed

    Picard, Brigitte; Kammoun, Malek; Gagaoua, Mohammed; Barboiron, Christiane; Meunier, Bruno; Chambon, Christophe; Cassar-Malek, Isabelle

    2016-05-04

    Hsp27-encoded by HspB1- is a member of the small heat shock proteins (sHsp, 12-43 kDa (kilodalton)) family. This protein is constitutively present in a wide variety of tissues and in many cell lines. The abundance of Hsp27 is highest in skeletal muscle, indicating a crucial role for muscle physiology. The protein identified as a beef tenderness biomarker was found at a crucial hub in a functional network involved in beef tenderness. The aim of this study was to analyze the proteins impacted by the targeted invalidation of HspB1 in the Tibialis anterior muscle of the mouse . Comparative proteomics using two-dimensional gel electrophoresis revealed 22 spots that were differentially abundant between HspB1 -null mice and their controls that could be identified by mass spectrometry. Eighteen spots were more abundant in the muscle of the mutant mice, and four were less abundant. The proteins impacted by the absence of Hsp27 belonged mainly to calcium homeostasis (Srl and Calsq1), contraction (TnnT3), energy metabolism (Tpi1, Mdh1, PdhB, Ckm, Pygm, ApoA1) and the Hsp proteins family (HspA9). These data suggest a crucial role for these proteins in meat tenderization. The information gained by this study could also be helpful to predict the side effects of Hsp27 depletion in muscle development and pathologies linked to small Hsps.

  20. Perspective on the impact of weightlessness on calcium and bone metabolism.

    PubMed

    Holick, M F

    1998-05-01

    As humans venture into space to colonize the moon and travel to distant planets in the 21st century, they will be confronted with a bone disease that could potentially limit their space exploration activities or put them at risk for fracture when they return to earth. It is now recognized that an unloading of the skeleton, either due to strict bed rest or in zero gravity, leads on average to a 1%-2% reduction in bone mineral density at selected skeletal sites each month. The mechanism by which unloading of the skeleton results in rapid mobilization of calcium stores from the skeleton is not fully understood, but it is thought to be related to down regulation in PTH and 1,25-dihydroxyvitamin D3 production. Bone modeling and mineralization in chick embryos is not affected by microgravity, suggesting that bone cells adapt and ultimately become addicted to gravity in order to maintain a structurally sound skeleton. Strategies need to be developed to decrease microgravity-induced bone resorption by either mimicking gravity's effect on bone metabolism, or enhancing physically or pharmacologically bone formation in order to preserve astronauts' bone health.

  1. Perspective on the impact of weightlessness on calcium and bone metabolism

    NASA Technical Reports Server (NTRS)

    Holick, M. F.

    1998-01-01

    As humans venture into space to colonize the moon and travel to distant planets in the 21st century, they will be confronted with a bone disease that could potentially limit their space exploration activities or put them at risk for fracture when they return to earth. It is now recognized that an unloading of the skeleton, either due to strict bed rest or in zero gravity, leads on average to a 1%-2% reduction in bone mineral density at selected skeletal sites each month. The mechanism by which unloading of the skeleton results in rapid mobilization of calcium stores from the skeleton is not fully understood, but it is thought to be related to down regulation in PTH and 1,25-dihydroxyvitamin D3 production. Bone modeling and mineralization in chick embryos is not affected by microgravity, suggesting that bone cells adapt and ultimately become addicted to gravity in order to maintain a structurally sound skeleton. Strategies need to be developed to decrease microgravity-induced bone resorption by either mimicking gravity's effect on bone metabolism, or enhancing physically or pharmacologically bone formation in order to preserve astronauts' bone health.

  2. Calcium Homeostasis and Muscle Energy Metabolism Are Modified in HspB1-Null Mice

    PubMed Central

    Picard, Brigitte; Kammoun, Malek; Gagaoua, Mohammed; Barboiron, Christiane; Meunier, Bruno; Chambon, Christophe; Cassar-Malek, Isabelle

    2016-01-01

    Hsp27—encoded by HspB1—is a member of the small heat shock proteins (sHsp, 12–43 kDa (kilodalton)) family. This protein is constitutively present in a wide variety of tissues and in many cell lines. The abundance of Hsp27 is highest in skeletal muscle, indicating a crucial role for muscle physiology. The protein identified as a beef tenderness biomarker was found at a crucial hub in a functional network involved in beef tenderness. The aim of this study was to analyze the proteins impacted by the targeted invalidation of HspB1 in the Tibialis anterior muscle of the mouse. Comparative proteomics using two-dimensional gel electrophoresis revealed 22 spots that were differentially abundant between HspB1-null mice and their controls that could be identified by mass spectrometry. Eighteen spots were more abundant in the muscle of the mutant mice, and four were less abundant. The proteins impacted by the absence of Hsp27 belonged mainly to calcium homeostasis (Srl and Calsq1), contraction (TnnT3), energy metabolism (Tpi1, Mdh1, PdhB, Ckm, Pygm, ApoA1) and the Hsp proteins family (HspA9). These data suggest a crucial role for these proteins in meat tenderization. The information gained by this study could also be helpful to predict the side effects of Hsp27 depletion in muscle development and pathologies linked to small Hsps. PMID:28248227

  3. Evolving Role of Molecular Imaging with (18)F-Sodium Fluoride PET as a Biomarker for Calcium Metabolism.

    PubMed

    Raynor, William; Houshmand, Sina; Gholami, Saeid; Emamzadehfard, Sahra; Rajapakse, Chamith S; Blomberg, Björn Alexander; Werner, Thomas J; Høilund-Carlsen, Poul F; Baker, Joshua F; Alavi, Abass

    2016-08-01

    (18)F-sodium fluoride (NaF) as an imaging tracer portrays calcium metabolic activity either in the osseous structures or in soft tissue. Currently, clinical use of NaF-PET is confined to detecting metastasis to the bone, but this approach reveals indirect evidence for disease activity and will have limited use in the future in favor of more direct approaches that visualize cancer cells in the read marrow where they reside. This has proven to be the case with FDG-PET imaging in most cancers. However, a variety of studies support the application of NaF-PET to assess benign osseous diseases. In particular, bone turnover can be measured from NaF uptake to diagnose osteoporosis. Several studies have evaluated the efficacy of bisphosphonates and their lasting effects as treatment for osteoporosis using bone turnover measured by NaF-PET. Additionally, NaF uptake in vessels tracks calcification in the plaques at the molecular level, which is relevant to coronary artery disease. Also, NaF-PET imaging of diseased joints is able to project disease progression in osteoarthritis, rheumatoid arthritis, and ankylosing spondylitis. Further studies suggest potential use of NaF-PET in domains such as back pain, osteosarcoma, stress-related fracture, and bisphosphonate-induced osteonecrosis of the jaw. The critical role of NaF-PET in disease detection and characterization of many musculoskeletal disorders has been clearly demonstrated in the literature, and these methods will become more widespread in the future. The data from PET imaging are quantitative in nature, and as such, it adds a major dimension to assessing disease activity.

  4. Stress in Obesity and Associated Metabolic and Cardiovascular Disorders

    PubMed Central

    Holvoet, Paul

    2012-01-01

    Obesity has significant implications for healthcare, since it is a major risk factor for both type 2 diabetes and the metabolic syndrome. This syndrome is a common and complex disorder combining obesity, dyslipidemia, hypertension, and insulin resistance. It is associated with high atherosclerotic cardiovascular risk, which can only partially be explained by its components. Therefore, to explain how obesity contributes to the development of metabolic and cardiovascular disorders, more and better insight is required into the effects of personal and environmental stress on disease processes. In this paper, we show that obesity is a chronic inflammatory disease, which has many molecular mechanisms in common with atherosclerosis. Furthermore, we focus on the role of oxidative stress associated with obesity in the development of the metabolic syndrome. We discuss how several stress conditions are related to inflammation and oxidative stress in association with obesity and its complications. We also emphasize the relation between stress conditions and the deregulation of epigenetic control mechanisms by means of microRNAs and show how this impairment further contributes to the development of obesity, closing the vicious circle. Finally, we discuss the limitations of current anti-inflammation and antioxidant therapy to treat obesity. PMID:24278677

  5. Effect of Intermittent Exposure to 3% CO2 on Respiration, Acid-Base Balance, and Calcium-Phosphorus Metabolism

    DTIC Science & Technology

    1978-03-01

    of the renal functions primarily involved in acid- base regulations are shown in Fig. 7. There was an immediate response to C02 breathing on the first...1965). Based on the available data, it is not possible to explain why the renal response was turned off on Day 2. At the fourth and fifth days... base balance, and calcium-phosphorus metabolism K. E. SCHAEFER, C. R. CAREY, J. H. DOUGHERTY, JR., C. MORGAN, and A. A. MESSIER Naval Submarine

  6. Cortisol dysregulation in obesity-related metabolic disorders

    PubMed Central

    Baudrand, Rene; Vaidya, Anand

    2015-01-01

    Purpose of review The understanding of how adrenal function is challenged by the interplay of our genetic and environmental milieu has highlighted the importance of inappropriate cortisol regulation in cardiometabolic disorders. Increased adipose tissue in obesity is associated with hypothalamic-pituitary-adrenal axis over-activation, increased cortisol production at the local tissue level, and probably higher mineralocorticoid receptor activation in certain tissues. Recent findings Due to the clinical resemblance of obesity-related metabolic disorders with the Cushing syndrome, new studies have investigated the intracellular regulation and metabolism of cortisol, new measurements in scalp hair as a tool for long-term exposure and the cortisol-mineralocorticoid receptor pathway. Thus, current and future pharmacological interventions in obesity may include specific inhibition of steroidogenic and regulatory enzymes as well as antagonists of the mineralocorticoid and glucocorticoid receptors. Summary This review highlights recent investigations focusing on the role of dysregulated cortisol physiology in obesity as a potential modifiable mechanism in the pathogenesis of obesity related cardiometabolic disorders. PMID:25871955

  7. Influence of calcium and phosphorus feeding on markers of bone metabolism in transition cows.

    PubMed

    Moreira, V R; Zeringue, L K; Williams, C C; Leonardi, C; McCormick, M E

    2009-10-01

    A study was carried out to verify the effect of Ca and P levels on production, digestibility, and serum bone metabolism biomarkers in dairy cows. Fifty-two nonlactating multiparous cows (>or=3 lactations) were confined in a free-stall barn approximately 20 d before calving. A standard close-up diet was fed to cows once daily until d 2 postpartum. Cows were randomly assigned to 1 of 4 dietary treatments arranged in a 2 x 2 factorial approach averaging 0.64% Ca for high Ca (HCa), 0.46% Ca for low Ca (LCa), 0.47% P for high P (HP), and 0.38% P for low P (LP) on a dry matter basis. Experimental diets were fed twice daily from 3 d in milk (DIM) until 31 DIM. Intake and milk yield were recorded daily. Milk samples were collected on d 28, 29, and 30 postpartum for components analyses. Blood samples were drawn 10 d before expected calving, at calving, and at 15 and 30 DIM for serum analyses of osteocalcin, a biomarker of bone accretion, and pyridinoline, a biomarker of bone resorption. Total fecal collection was conducted when cows in a block averaged 20 DIM. Intake and production traits were not significantly affected by any of the dietary treatments. Cows averaged nearly 21 kg/d dry matter intake and 44 kg/d milk yield from 6 to 31 DIM. There were no significant differences across treatments in body weight or body condition score loss. Phosphorus intake, P fecal output, P digestibility, and P apparent absorption were affected by dietary P content. Calcium intake was higher with HCa, but Ca fecal output, digestibility, and apparent absorption showed an interaction between dietary Ca and dietary P. Calcium fecal output was 100.6 g/d for cows fed HCaHP, intermediate for cows on the HCaLP diet (89 g/d), and similar among cows fed the 2 LCa diets (70 g/d with LCaHP and 75 with LCaLP). There was no significant effect of Ca or P on osteocalcin measurements. Pyridinoline concentrations were affected by dietary Ca levels and tended to have a significant dietary Ca x dietary P

  8. Development of the Clinic of Endocrinology, diabetes and metabolic disorders.

    PubMed

    Shubeska Stratrova, S

    2013-01-01

    The Clinic of Endocrinology, diabetes and metabolic disorders was founded in 1975 by Prof d-r Alexandar Plashevski. Healthcare, educational and scientific activities in the Clinic of Endocrinology are performed in its departments. The Department for hospitalized diabetic and endocrine patients consists of the metabolic and endocrine intensive care unit, the department for diagnosis and treatment of diabetics and endocrine patients, day hospital, the department for education of diabetic patients, and the national center for insulin pump therapy. The Center for Diabetes was established in 1972 by Prof d-r Dimitar Arsov. In 1975, Prof d-r Alexandar Plasheski broadened the activities of the Center for Diabetes. It was dislocated in 1980, with new accommodation outside the clinic. Since then the Center has consisted of several organized units: two specialist outpatient clinics for diabetic patients, biochemical and endocrine laboratory, sub-departments for: diabetic foot, cardiovascular diagnosis, ophthalmology, and urgent interventions. The Department of Endocrinology and Metabolic Disorders for outclinic endocrine patients was established in 1980, and it integrates the following sub-departments: thyrology, andrology, reproductive endocrinology, obesity and lipid disorders and sub-department for osteoporosis. The educational staff of the Clinic of Endocrinology organizes theoretical and practical education about Clinical Investigation and Internal Medicine with credit transfer system course of study of the Medical Faculty, Faculty of Stomatology, postgraduate studies, specializations and sub-specializations. Symposiums, 3 congresses, schools for diabetes and osteoporosis and continuous medical education were also organized. The Clinic of Endocrinology was initiator, organizer, founder and the seat of several medical associations.

  9. Calcium Channel Genes Associated with Bipolar Disorder Modulate Lithium's Amplification of Circadian Rhythms

    PubMed Central

    McCarthy, Michael J.; LeRoux, Melissa; Wei, Heather; Beesley, Stephen; Kelsoe, John R.; Welsh, David K.

    2015-01-01

    Bipolar disorder (BD) is associated with mood episodes and low amplitude circadian rhythms. Previously, we demonstrated that fibroblasts grown from BD patients show weaker amplification of circadian rhythms by lithium compared to control cells. Since calcium signals impact upon the circadian clock, and L-type calcium channels (LTCC) have emerged as genetic risk factors for BD, we examined whether loss of function in LTCCs accounts for the attenuated response to lithium in BD cells. We used fluorescent dyes to measure Ca2+ changes in BD and control fibroblasts after lithium treatment, and bioluminescent reporters to measure Per2∷luc rhythms in fibroblasts from BD patients, human controls, and mice while pharmacologically or genetically manipulating calcium channels. Longitudinal expression of LTCC genes (CACNA1C, CACNA1D and CACNB3) was then measured over 12-24 hr in BD and control cells. Our results indicate that independently of LTCCs, lithium stimulated intracellular Ca2+ less effectively in BD vs. control fibroblasts. In longitudinal studies, pharmacological inhibition of LTCCs or knockdown of CACNA1A, CACNA1C, CACNA1D and CACNB3 altered circadian rhythm amplitude. Diltiazem and knockdown of CACNA1C or CACNA1D eliminated lithium's ability to amplify rhythms. Knockdown of CACNA1A or CACNB3 altered baseline rhythms, but did not affect rhythm amplification by lithium. In human fibroblasts, CACNA1C genotype predicted the amplitude response to lithium, and the expression profiles of CACNA1C, CACNA1D and CACNB3 were altered in BD vs. controls. We conclude that in cells from BD patients, calcium signaling is abnormal, and that LTCCs underlie the failure of lithium to amplify circadian rhythms. PMID:26476274

  10. Disorders of carbohydrate or lipid metabolism in camelids.

    PubMed

    Cebra, Christopher K

    2009-07-01

    Camelids develop a number of disturbances related to energy metabolism. Some are similar to disorders seen in other species, but most relate to camelids' unusual characteristics of poor glucose tolerance, partial insulin resistance, and low concentrations of circulating insulin. Camelids are especially prone to abnormalities related to stimuli that inhibit insulin release or activity, or that promote activities normally antagonized by insulin. These include stimuli that mobilize glycogen or fat stores, or inhibit glucose uptake or intravascular glycolysis. These stimuli are generally more important than negative energy balance in triggering these disorders. Treatment must concentrate on the hormonal aspects, and not just provision of energy. Treatments related to hormonal aspects include those to decrease catecholamine release and to provide exogenous insulin until the camelid is again able to maintain appropriate energy substrate homeostasis.

  11. Disruption of Calcium Homeostasis During Exercise as a Mediator of Bone Metabolism

    DTIC Science & Technology

    2015-10-01

    Meeting of the American College of Sports Medicine (Appendix A). 15. SUBJECT TERMS calcium homeostasis, exercise, bone resorption, parathyroid hormone ... hormone (PTH). PTH can defend serum Ca by reducing urinary Ca excretion, increasing intestinal Ca absorption, and increasing mobilization of skeletal Ca...certain conditions. It is our contention that disruptions in calcium homeostasis during exercise lead to increases in parathyroid hormone (PTH) and

  12. Maternal consumption of dairy products, calcium, and vitamin D during pregnancy and infantile allergic disorders.

    PubMed

    Miyake, Yoshihiro; Tanaka, Keiko; Okubo, Hitomi; Sasaki, Satoshi; Arakawa, Masashi

    2014-07-01

    Epidemiologic evidence of the association between maternal intake of dairy foods, calcium, and vitamin D during pregnancy and childhood allergic disorders is inconclusive. To examine the association between maternal intake of dairy foods, calcium, and vitamin D during pregnancy and childhood allergic disorders in Japanese children aged 23 to 29 months. Study participants were 1,354 mother-child pairs. Maternal intake during pregnancy was assessed with a validated diet history questionnaire administered between April 2007 and March 2008. Wheeze and eczema, defined according to criteria of the International Study of Asthma and Allergies in Childhood, and physician-diagnosed asthma and atopic eczema were assessed via a questionnaire completed by mothers. Higher maternal intake of total dairy products during pregnancy was significantly associated with a reduced risk of infantile eczema (adjusted odds ratio [OR] between extreme quartiles, 0.64; 95% confidence interval [CI], 0.42-0.98). Higher maternal intake of cheese during pregnancy was significantly related to a reduced risk of physician-diagnosed infantile asthma (adjusted OR between extreme quartiles, 0.44; 95% CI, 0.18-0.97). Maternal intake levels of yogurt and calcium during pregnancy were significantly inversely associated with physician-diagnosed infantile atopic eczema (adjusted ORs between extreme quartiles, 0.49 and 0.34; 95% CI, 0.20-1.16 and 0.12-0.84; P for trend = .01 and .03, respectively). Maternal intake of vitamin D during pregnancy was significantly positively associated with infantile eczema (adjusted OR between extreme quartiles, 1.63; 95% CI, 1.07-2.51). Higher maternal intake of total dairy products, cheese, yogurt, and calcium during pregnancy may reduce the risk of infantile eczema, physician-diagnosed asthma, physician-diagnosed atopic eczema, and physician-diagnosed atopic eczema, respectively. Higher maternal intake of vitamin D during pregnancy may increase the risk of infantile eczema

  13. Hepatocyte transplantation for liver-based metabolic disorders.

    PubMed

    Dhawan, Anil; Mitry, Ragai R; Hughes, Robin D

    2006-01-01

    Hepatocyte transplantation is being investigated as an alternative to orthotopic liver transplantation in patients with liver-based metabolic disorders. The progress made in this field to date is reviewed. Protocols have been developed using collagenase perfusion to isolate human hepatocytes from unused donor liver tissue. Hepatocytes with a high viability can often be obtained and can be cryopreserved for later use, though with loss of function on thawing. For clinical use, hepatocytes must be prepared in clean GMP conditions with cells meeting criteria of function and lack of microbial contamination before patient use. Hepatocytes are infused intraportally into the patient's liver, where a proportion of cells will engraft and replace the deficient metabolic function without the need for major surgery. Twenty patients have now received hepatocyte transplantation, including eight children at King's College Hospital. There was a range of aetiologies of liver disease: familial hypercholesterolaemia, Crigler-Najjar syndrome type 1, urea cycle defects, infantile Refsum disease, glycogen storage disease type Ia, inherited factor VII deficiency and progressive familial intrahepatic cholestasis type 2. Clinical improvement and partial correction of the metabolic abnormality was observed in most cases. Considerable progress has been made in developing the technique, but hepatocyte transplantation is limited by the available supply of liver tissue. Hepatocytes derived from stem cells could provide alternative sources of cells in the future.

  14. Metabolic and Homeostatic Changes in Seizures and Acquired Epilepsy—Mitochondria, Calcium Dynamics and Reactive Oxygen Species

    PubMed Central

    Kovac, Stjepana; Dinkova Kostova, Albena T.; Melzer, Nico; Meuth, Sven G.; Gorji, Ali

    2017-01-01

    Acquired epilepsies can arise as a consequence of brain injury and result in unprovoked seizures that emerge after a latent period of epileptogenesis. These epilepsies pose a major challenge to clinicians as they are present in the majority of patients seen in a common outpatient epilepsy clinic and are prone to pharmacoresistance, highlighting an unmet need for new treatment strategies. Metabolic and homeostatic changes are closely linked to seizures and epilepsy, although, surprisingly, no potential treatment targets to date have been translated into clinical practice. We summarize here the current knowledge about metabolic and homeostatic changes in seizures and acquired epilepsy, maintaining a particular focus on mitochondria, calcium dynamics, reactive oxygen species and key regulators of cellular metabolism such as the Nrf2 pathway. Finally, we highlight research gaps that will need to be addressed in the future which may help to translate these findings into clinical practice. PMID:28885567

  15. Magnesium retention from metabolic-balance studies in female adolescents: impact of race, dietary salt, and calcium123

    PubMed Central

    Palacios, Cristina; Wigertz, Karin; Braun, Michelle; Martin, Berdine R; McCabe, George P; McCabe, Linda; Pratt, J Howard; Peacock, Munro; Weaver, Connie M

    2013-01-01

    Background: Previously, we showed that black girls retained more calcium than white girls did and that salt loading negatively affected calcium retention. Racial differences likely exist in other bone minerals also, such as magnesium, in response to salt loading during growth. Objective: We studied racial differences in magnesium metabolism in response to dietary sodium and calcium during rapid bone growth. Design: Twenty-seven white and 40 black girls (11–15 y old) were studied for 3 wk while they consumed low-sodium (1.3 g/d) and high-sodium (3.8 g/d) diets by using a randomized-order, crossover metabolic study with 3 dietary calcium intakes; the magnesium dietary intake was fixed at 230 mg/d. Urine and feces were collected during each 3-wk period in 24-h pools and analyzed for magnesium. A mixed-model ANOVA was used to determine the effect of race and dietary sodium with calcium intake as a covariate. Results: Salt loading or calcium intake had no significant effect on urinary magnesium excretion. Blacks excreted significantly less urinary magnesium (mean ± SD: 83.8 ± 25.6 mg/d) than did whites (94.9 ± 27.3 mg/d; P < 0.05). No effects were observed in fecal magnesium excretion. Magnesium retention was higher with the low-sodium diet (50.1 ± 44.0 mg/d) than with the high-sodium diet (39.3 ± 49.8 mg/d) (P < 0.05), with no effects of race or calcium intake. Salt loading had no effect on biomarkers. Whites had higher 25-hydroxyvitamin D and insulin-like growth factor binding protein 3 but lower 1,25-dihydroxyvitamin D and parathyroid hormone concentrations. Conclusions: Blacks excreted less urinary magnesium than did whites. Magnesium retention was similar between races but higher with the low-sodium diet. Kinetic studies are needed to fully explain magnesium homeostasis. This trial was registered at clinicaltrials.gov as NCT01564238. PMID:23553157

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

    PubMed

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

    2015-01-02

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

  17. Delay in onset of metabolic alkalosis during regional citrate anti-coagulation in continuous renal replacement therapy with calcium-free replacement solution.

    PubMed

    See, Kay Choong; Lee, Margaret; Mukhopadhyay, Amartya

    2009-01-01

    Regional citrate anti-coagulation for continuous renal replacement therapy chelates calcium to produce the anti- coagulation effect. We hypothesise that a calcium-free replacement solution will require less citrate and produce fewer metabolic side effects. Fifty patients, in a Medical Intensive Care Unit of a tertiary teaching hospital (25 in each group), received continuous venovenous hemofiltration using either calcium-containing or calcium-free replacement solutions. Both groups had no significant differences in filter life, metabolic alkalosis, hypernatremia, hypocalcemia, and hypercalcemia. However, patients using calcium-containing solution developed metabolic alkalosis earlier, compared to patients using calcium-free solution (mean 24.6 hours,CI 0.8-48.4 vs. 37.2 hours, CI 9.4-65, P = 0.020). When calcium-containing replacement solution was used, more citrate was required (mean 280 ml/h, CI 227.2-332.8 vs. 265 ml/h, CI 203.4-326.6, P = 0.069), but less calcium was infused (mean 21.2 ml/h, CI 1.2-21.2 vs 51.6 ml/h, CI 26.8-76.4, P < or = 0.0001).

  18. Changes in bone metabolic parameters following oral calcium supplementation in an adult patient with vitamin D-dependent rickets type 2A.

    PubMed

    Kinoshita, Yuka; Ito, Nobuaki; Makita, Noriko; Nangaku, Masaomi; Fukumoto, Seiji

    2017-06-29

    Vitamin D-dependent rickets type 2A (VDDR2A) is a rare inherited disorder with decreased tissue responsiveness to 1,25-dihydroxyvitamin D [1,25(OH) 2 D], caused by loss of function mutations in the vitamin D receptor (VDR) gene. Approximately 50 types of mutations have been identified so far that change amino acids in either the N-terminal DNA binding domain (DBD) or the C-terminal ligand binding domain (LBD) of the VDR protein. The degree of responsiveness to 1,25(OH) 2 D varies between patients with VDDR2A, which may depend on their residual VDR function. In this report, we describe a female patient with VDDR2A caused by an early stop codon (R30X) in the VDR gene that resulted in a severely truncated VDR protein. She developed alopecia and bowed legs within a year after birth and was diagnosed with rickets at the age of 2. She had been treated with active vitamin D and oral calcium supplementation until 22 years of age, when she developed secondary hyperparathyroidism and high bone turnover. The genetic diagnosis of VDDR2A promoted the discontinuation of active vitamin D treatment in favor of monotherapy with oral calcium supplementation. We observed amelioration of the secondary hyperparathyroidism and normalization of bone metabolic parameters within 6 years.

  19. Phosphate binders and metabolic acidosis in patients undergoing maintenance hemodialysis—sevelamer hydrochloride, calcium carbonate, and bixalomer.

    PubMed

    Sanai, Toru; Tada, Hideo; Ono, Takashi; Fukumitsu, Toma

    2015-01-01

    The serum bicarbonate (HCO3(-)) levels are decreased in chronic hemodialysis (HD) patients treated with sevelamer hydrochloride (SH). We assessed the effects of bixalomer on the chronic metabolic acidosis in these patients. We examined 12 of the 122 consecutive Japanese patients with end-stage renal disease on HD, who orally ingested a dose of SH (≥2250 mg), and an arterial blood gas analysis and biochemical analysis were performed before HD. Patients whose serum HCO3(-) levels were under 18 mmol/L were changed from SH to the same dose of bixalomer. A total of 12 patients were treated with a large amount of SH. Metabolic acidosis (a serum HCO3(-) level under 18 mmol/L) was found in eight patients. These patients were also treated with or without small dose of calcium carbonate (1.2 ± 1.1 g). The dose of SH was changed to that of bixalomer. After 1 month, the serum HCO3(-) levels increased from 16.3 ± 1.4 to 19.6 ± 1.7 mmol/L (P < 0.05). Metabolic acidosis was not observed in four patients (serum HCO3(-) level: 20.3 ± 0.7 mmol/L) likely because they were taking 3 g of calcium carbonate with SH. In the present study, the development of chronic metabolic acidosis was induced by HCl containing phosphate binders, such as SH, and partially ameliorated by calcium carbonate, then subsequently improved after changing the treatment to bixalomer. © 2014 Fukumitsu Hospital. Hemodialysis International published by Wiley Periodicals, Inc. on behalf of International Society for Hemodialysis.

  20. Parameters for calcium metabolism in women with polycystic ovary syndrome who undergo clomiphene citrate stimulation: a prospective cohort study.

    PubMed

    Ott, J; Wattar, L; Kurz, C; Seemann, R; Huber, J C; Mayerhofer, K; Vytiska-Binstorfer, E

    2012-05-01

    To evaluate whether parameters for calcium metabolism were associated with characteristics of polycystic ovary syndrome (PCOS). A prospective cohort study. Ninety-one anovulatory, infertile women with PCOS patients underwent clomiphene citrate (CC) stimulation. Main outcome measures were parathyroid hormone (PTH); 25-hydroxyvitamin D3 (25OHD3); serum levels of calcium, phosphorus, magnesium, albumin, and total protein; the serum calcium-phosphorus product; LH; FSH; sexual hormone binding globulin; testosterone; and androstenedione. PTH correlated inversely with serum calcium (r=-0.235; P=0.004) and 25OHD3 (r=-0.664; P<0.001), whereas positive correlations were found between PTH and body mass index (BMI; r=0.270; P=0.010) and between PTH and testosterone (r=0.347; P=0.001). After stimulation with 50 mg CC, 57.1% (52/91) developed a follicle, whereas 26.4% (24/91) became pregnant. In a multivariate model to predict both follicle development and pregnancy, BMI and 25OHD3 deficiency were significant predictive parameters. 25OHD3 deficiency was an independent predictive parameter of CC stimulation outcome, in terms of follicle development and pregnancy. Our results suggest a substantial role of vitamin D in PCOS and infertility treatment in these patients.

  1. Mitochondrial-associated metabolic disorders: foundations, pathologies and recent progress

    PubMed Central

    2013-01-01

    Research in the last decade has revolutionized the way in which we view mitochondria. Mitochondria are no longer viewed solely as cellular powerhouses; rather, mitochondria are now understood to be vibrant, mobile structures, constantly undergoing fusion and fission, and engaging in intimate interactions with other cellular compartments and structures. Findings have implicated mitochondria in a wide variety of cellular processes and molecular interactions, such as calcium buffering, lipid flux, and intracellular signaling. As such, it does not come as a surprise that an increasing number of human pathologies have been associated with functional defects in mitochondria. The difficulty in understanding and treating human pathologies caused by mitochondrial dysfunction arises from the complex relationships between mitochondria and other cellular processes, as well as the genetic background of such diseases. This review attempts to provide a summary of the background knowledge and recent developments in mitochondrial processes relating to mitochondrial-associated metabolic diseases arising from defects or deficiencies in mitochondrial function, as well as insights into current and future avenues for investigation. PMID:24499129

  2. Metabolic syndrome in patients with depressive disorder--features of comorbidity.

    PubMed

    Kozumplik, Oliver; Uzun, Suzana

    2011-03-01

    Depression is associated with increased physical morbidity and overall mortality. The results of a previous investigation on the relationship of the metabolic syndrome and its single components with coronary heart disease, cardiovascular disease (CVD), and all-cause mortality suggested that the metabolic syndrome is a marker of CVD risk, but not above and beyond the risk associated with its individual components. The aim of this article is to review literature regarding prevalence of metabolic syndrome in patients with depressive disorder, and association between metabolic syndrome and depression. Literature research included structured searches of Medline and other publications on the subject of metabolic syndrome, particularly prevalence of metabolic syndrome in patients with depressive disorder, and association between metabolic syndrome and depression. Prevalence of the metabolic syndrome in patients with depression is high and varies among the analysed studies. Some investigations showed association between metabolic syndrome and depression. Further investigations are necessary in order to clarify the association between metabolic syndrome and depression.

  3. Altered lipid metabolism in brain injury and disorders.

    PubMed

    Adibhatla, Rao Muralikrishna; Hatcher, J F

    2008-01-01

    Deregulated lipid metabolism may be of particular importance for CNS injuries and disorders, as this organ has the highest lipid concentration next to adipose tissue. Atherosclerosis (a risk factor for ischemic stroke) results from accumulation of LDL-derived lipids in the arterial wall. Pro-inflammatory cytokines (TNF-alpha and IL-1), secretory phospholipase A2 IIA and lipoprotein-PLA2 are implicated in vascular inflammation. These inflammatory responses promote atherosclerotic plaques, formation and release of the blood clot that can induce ischemic stroke. TNF-alpha and IL-1 alter lipid metabolism and stimulate production of eicosanoids, ceramide, and reactive oxygen species that potentiate CNS injuries and certain neurological disorders. Cholesterol is an important regulator of lipid organization and the precursor for neurosteroid biosynthesis. Low levels of neurosteroids were related to poor outcome in many brain pathologies. Apolipoprotein E is the principal cholesterol carrier protein in the brain, and the gene encoding the variant Apolipoprotein E4 is a significant risk factor for Alzheimer's disease. Parkinson's disease is to some degree caused by lipid peroxidation due to phospholipases activation. Niemann-Pick diseases A and B are due to acidic sphingomyelinase deficiency, resulting in sphingomyelin accumulation, while Niemann-Pick disease C is due to mutations in either the NPC1 or NPC2 genes, resulting in defective cholesterol transport and cholesterol accumulation. Multiple sclerosis is an autoimmune inflammatory demyelinating condition of the CNS. Inhibiting phospholipase A2 attenuated the onset and progression of experimental autoimmune encephalomyelitis. The endocannabinoid system is hypoactive in Huntington's disease. Ethyl-eicosapetaenoate showed promise in clinical trials. Amyotrophic lateral sclerosis causes loss of motorneurons. Cyclooxygenase-2 inhibition reduced spinal neurodegeneration in amyotrophic lateral sclerosis transgenic mice

  4. Influence of different calcium concentrations in the diet on bone metabolism in growing dairy goats and sheep.

    PubMed

    Liesegang, A; Risteli, J

    2005-01-01

    The purpose of this study was to investigate, if different Ca concentrations in diets have an influence on bone mineral metabolism in growing goats and sheep. Twelve growing goats and sheep were divided into two groups. The two control groups received 6.1 g calcium/day (nG) and 6.7 g calcium/day (nS) for goat and sheep respectively. The other two groups were fed 17.7 g calcium/day (hG) and 18.5 g calcium/day (hS). Blood samples were taken 2, 4, 5 and 6 weeks after the start of the experiment. In serum Ca and vitamin D were determined and bone metabolism was measured using crosslinked carboxyterminal telopeptide of type I collagen (ICTP), crosslaps, bone-specific alkaline phosphatase and osteocalcin (OC). Bone mineral density (BMD) was quantified using quantitative computed tomography. Bone resorption marker (ICTP) concentrations were significantly different between both groups control sheep/control goat and hS/hG, but no significant differences were evident in the different feeding groups within one species. OC concentrations showed a similar course to ICTP. The goats had significantly higher concentrations compared with sheep. The 1,25 dihydroxyvitamin D (VITD) concentrations in both hCa groups were significantly lower than in the control groups. BMD increased in the hCa groups compared with the control groups with the time, but significant differences were only evident in sheep in week 2. The hCa diet did not induce differences between the groups within one species for all bone markers. The control Ca diet seems to improve the active Ca absorption via VITD whereas the hCa diet leads to a higher amount of Ca apparently digested. Higher BMD was only observed in group hS compared with nS.

  5. Role of acidosis-induced increases in calcium on PTH secretion in acute metabolic and respiratory acidosis in the dog.

    PubMed

    López, Ignacio; Aguilera-Tejero, Escolástico; Estepa, José Carlos; Rodríguez, Mariano; Felsenfeld, Arnold J

    2004-05-01

    Recently, we showed that both acute metabolic acidosis and respiratory acidosis stimulate parathyroid hormone (PTH) secretion in the dog. To evaluate the specific effect of acidosis, ionized calcium (iCa) was clamped at a normal value. Because iCa values normally increase during acute acidosis, we now have studied the PTH response to acute metabolic and respiratory acidosis in dogs in which the iCa concentration was allowed to increase (nonclamped) compared with dogs with a normal iCa concentration (clamped). Five groups of dogs were studied: control, metabolic (clamped and nonclamped), and respiratory (clamped and nonclamped) acidosis. Metabolic (HCl infusion) and respiratory (hypoventilation) acidosis was progressively induced during 60 min. In the two clamped groups, iCa was maintained at a normal value with an EDTA infusion. Both metabolic and respiratory acidosis increased (P < 0.05) iCa values in nonclamped groups. In metabolic acidosis, the increase in iCa was progressive and greater (P < 0.05) than in respiratory acidosis, in which iCa increased by 0.04 mM and then remained constant despite further pH reductions. The increase in PTH values was greater (P < 0.05) in clamped than in nonclamped groups (metabolic and respiratory acidosis). In the nonclamped metabolic acidosis group, PTH values first increased and then decreased from peak values when iCa increased by > 0.1 mM. In the nonclamped respiratory acidosis group, PTH values exceeded (P < 0.05) baseline values only after iCa values stopped increasing at a pH of 7.30. For the same increase in iCa in the nonclamped groups, PTH values increased more in metabolic acidosis. In conclusion, 1) both metabolic acidosis and respiratory acidosis stimulate PTH secretion; 2) the physiological increase in the iCa concentration during the induction of metabolic and respiratory acidosis reduces the magnitude of the PTH increase; 3) in metabolic acidosis, the increase in the iCa concentration can be of sufficient

  6. [METABOLIC SYNDROME AND CARDIOVASCULAR RISK IN PATIENTS WITH SCHIZOPHRENIA, BIPOLAR DISORDER AND SCHIZOAFFECTIVE DISORDER].

    PubMed

    Muñoz-Calero Franco, Paloma; Sánchez Sánchez, Blanca; Rodríguez Criado, Natalia; Pinilla Santos, Berta; Bravo Herrero, Sandra; Cruz Fourcade, José Fernando; Martín Aragón, Rubén

    2015-12-01

    patients with severe mental ilness such as schizophrenia, schizoaffective disorder and bipolar disorder die at least 20 years earlier than general population. Despite preventive strategies, cardiovascular disease is the first cause of death. analyse the percentage of patients with a high body mass index, metabolic syndrome and their cardiovascular risk at 10 years in patients with a diagnosis, based in DSM-IV criteria for schizophrenia, schizoaffective disorder or bipolar disorder. These patients were hospitalized because and acute condition of their mental ilness in the Brief Hospitalization Unit of Hospital Universitario de Móstoles between November of 2014 and June of 2015. in 53 patients, 34 with a diagnosis of schizophrenia, 16 with a diagnosis of bipolar disorder and 3 with a schizoaffective disorder, weight, size abdominal perimeter measures and blood pressure were collected. The body mass index was assesed. Blood tests were taken and we use sugar, triglycerides, total cholesterol and HDL cholesterol levels as paramethers for the ATP III and Framingham criteria. We also review the clinical history of the patients and lifestyle and use of toxic substances were registered. 51% of the patients were men and 49% were women. The average age was 40. 38% of the patients were overweighed, 22% obese and 4% had morbid obesity. 26% of the patients had metabolic syndrome, the clinical evolution of the majority of these patients was of more tan 10 years and they also have been treated with different antypsychotics and antidepressants. Using the Framingham criteria, 11% of the patients had a cardiovascular risk higher than 10 % in the next 10 years. overweight and its consequences in patients with a severe mental ilness are intimately related with their lifestyle, disparities in the access to health resources, the clinical evolution of the disease and pharmacotherapy. Strategies to promote physical health in these patients in the spanish health sistme are insufficient

  7. [Disorder of porphyrin metabolism in thallium intoxication (author's transl)].

    PubMed

    Graben, N; Doss, M; Klöppel, H A

    1978-08-04

    A 19-year old male ingested in suicidal attempt 750 mg of thallium. He developed the characteristic symptoms of thallium intoxication. During the acute phase the urinary excretion of porphyrins and porphyrin precursors was largely increased. The percentage distribution of the individual metabolites of heme synthesis revealed a preponderance of kopro- and uroporphyrin. This constellation (kopro- greater than uro- greater than tricarboxylic porphyrin) differs appreciably from that one in lead intoxication. The observation of increased urinary excretion of porphyrins and their precursors in a possibly particular spectrum in thallium intoxication is of special interest for differential-diagnostic reasoning. In each case of a toxic disorder of porphyrin metabolism thallium intoxication ought to be considered a possible cause.

  8. [Calcium and vitamin D in bone metabolism: Clinical importance for fracture treatment].

    PubMed

    Amling, M

    2015-12-01

    A balanced calcium homeostasis is of critical importance not only for bone remodeling, the physiological process of bone resorption and bone formation that constantly renews bone throughout life but also for normal fracture healing. Given that disturbances of calcium homeostasis are present in 50 % of the German population and that this might result in delayed fracture healing after correct surgical treatment, this paper focusses on calcium and vitamin D in the daily practice in orthopedics and trauma surgery. To ensure the required enteral calcium uptake the following three conditions are required: (1) sufficient calcium intake via the nutrition, (2) a 25-hydroxyvitamin D serum level > 30 µg/l and (3) the presence of sufficient gastric acidification. Given the endemic vitamin D deficiency in Germany as well as the constantly increasing number of people using proton pump inhibitors on a regular basis, it is necessary to closely connect trauma orthopedic surgery and osteological treatment. The first issue to be dealt with is to control and if needed normalize calcium homeostasis in order to allow a normal undisturbed fracture healing process after both conservative as well as operative treatment of fractures.

  9. Muscle mitochondrial metabolism and calcium signaling impairment in patients treated with statins

    SciTech Connect

    Sirvent, P., E-mail: pascal.sirvent@univ-bpclermont.fr; CHRU Montpellier, 34295 Montpellier; Clermont Université, Université Blaise Pascal, EA 3533, Laboratoire des Adaptations Métaboliques à l'Exercice en conditions Physiologiques et Pathologiques

    2012-03-01

    The most common and problematic side effect of statins is myopathy. To date, the patho-physiological mechanisms of statin myotoxicity are still not clearly understood. In previous studies, we showed that acute application in vitro of simvastatin caused impairment of mitochondrial function and dysfunction of calcium homeostasis in human and rat healthy muscle samples. We thus evaluated in the present study, mitochondrial function and calcium signaling in muscles of patients treated with statins, who present or not muscle symptoms, by oxygraphy and recording of calcium sparks, respectively. Patients treated with statins showed impairment of mitochondrial respiration that involved mainly the complexmore » I of the respiratory chain and altered frequency and amplitude of calcium sparks. The muscle problems observed in statin-treated patients appear thus to be related to impairment of mitochondrial function and muscle calcium homeostasis, confirming the results we previously reported in vitro. -- Highlights: ► The most common and problematic side effect of statins is myopathy. ► Patients treated with statins showed impairment of mitochondrial respiration. ► Statins-treated patients showed altered frequency and amplitude of calcium sparks.« less

  10. Calcium-Alkali Syndrome in the Modern Era

    PubMed Central

    Patel, Ami M.; Adeseun, Gbemisola A.; Goldfarb, Stanley

    2013-01-01

    The ingestion of calcium, along with alkali, results in a well-described triad of hypercalcemia, metabolic alkalosis, and renal insufficiency. Over time, the epidemiology and root cause of the syndrome have shifted, such that the disorder, originally called the milk-alkali syndrome, is now better described as the calcium-alkali syndrome. The calcium-alkali syndrome is an important cause of morbidity that may be on the rise, an unintended consequence of shifts in calcium and vitamin D intake in segments of the population. We review the pathophysiology of the calcium-alkali syndrome. PMID:24288027

  11. Cannabinoids and endocannabinoids in metabolic disorders with focus on diabetes.

    PubMed

    Di Marzo, Vincenzo; Piscitelli, Fabiana; Mechoulam, Raphael

    2011-01-01

    The cannabinoid receptors for Δ(9)-THC, and particularly, the CB(1) receptor, as well as its endogenous ligands, the endocannabinoids anandamide and 2-arachidonoylglycerol, are deeply involved in all aspects of the control of energy balance in mammals. While initially it was believed that this endocannabinoid signaling system would only facilitate energy intake, we now know that perhaps even more important functions of endocannabinoids and CB(1) receptors in this context are to enhance energy storage into the adipose tissue and reduce energy expenditure by influencing both lipid and glucose metabolism. Although normally well controlled by hormones and neuropeptides, both central and peripheral aspects of endocannabinoid regulation of energy balance can become dysregulated and contribute to obesity, dyslipidemia, and type 2 diabetes, thus raising the possibility that CB(1) antagonists might be used for the treatment of these metabolic disorders. On the other hand, evidence is emerging that some nonpsychotropic plant cannabinoids, such as cannabidiol, can be employed to retard β-cell damage in type 1 diabetes. These novel aspects of endocannabinoid research are reviewed in this chapter, with emphasis on the biological effects of plant cannabinoids and endocannabinoid receptor antagonists in diabetes.

  12. Fanconi Anemia complementation group C protein in metabolic disorders.

    PubMed

    Nepal, Manoj; Ma, Chi; Xie, Guoxiang; Jia, Wei; Fei, Peiwen

    2018-06-21

    Given importance of 22-Fanconi Anemia (FA) proteins together to act in a signaling pathway in preventing deleterious clinical symptoms, e.g. severe bone marrow failure, congenital defects, an early onset of aging and cancer, studies on each FA protein become increasingly attractive. However, an unbiased and systematic investigation of cellular effects resulting from each FA protein is missing. Here, we report roles of FA complementation C group protein (FANCC) in the protection from metabolic disorders. This study was prompted by the diabetes-prone feature displayed in FANCC knockout mice, which is not typically shown in patients with FA. We found that in cells expressing FANCC at different levels, there are representative alterations in metabolites associated with aging (glycine, citrulline, ornithine, L-asparagine, L-tyrosine, L-arginine, L-glutamine, L-leucine, L-isoleucine, L-valine, L-proline and L-alanine), Diabetes Mellitus (DM) (carbon monoxide, collagens, fatty acids, D-glucose, fumaric acid, 2-oxoglutaric acid, C3), inflammation (inosine, L-arginine, L-isoleucine, L-leucine, L-lysine, L-phenylalanine, hypoxanthine, L-methionine), and cancer ( L-methionine, sphingomyelin, acetyl-L-carnitine, L-aspartic acid, L-glutamic acid, niacinamide, phospho-rylethanolamine). We also found that FANCC can act in an FA-pathway-independent manner in tumor suppression. Collectively, featured-metabolic alterations are readouts of functional mechanisms underlying reduced tumorigenicity driven by FANCC, demonstrating close links among cancer, aging, inflammation and DM.

  13. [Metabolic disorders and adiposity in a rural population].

    PubMed

    Silva, Daniele A; Felisbino-Mendes, Mariana S; Pimenta, Adriano M; Gazzinelli, Andrea; Kac, Gilberto; Velásquez-Meléndez, Gustavo

    2008-04-01

    The aim of this cross-sectional study was to verify the prevalence of overweight and central adiposity (CA) in a sample of 287 adult subjects that lived in a rural community of Minas Gerais State. Means lipids, lipoproteins, glucose and blood pressure levels were compared according adiposity categories using One-way ANOVA and Tukey tests. Prevalence of overweight was 24.8% (37.4% for female; 11.5% for male). CA was verified in 28.1% of the individuals (50.3% for female; 4.3% for male). The associations between CA and overweight with the metabolic disorders: arterial hypertension (AH), dyslipidemia and hyperglycemia were estimated. Subjects with CA presented higher mean values of blood pressure, total cholesterol, LDL, triglycerides, fasting glucose, and lower mean values of HDL. CA was associated with AH, dyslipidemia and hyperglycemia. Associations between overweight and AH, dyslipidemia and hyperglycemia were also verified. These results confirm the potential effect of body composition shifting, especially at the abdominal level, on lipids, glucose metabolism and on blood pressure levels in rural populations.

  14. Chronic alcoholism-mediated metabolic disorders in albino rat testes.

    PubMed

    Shayakhmetova, Ganna M; Bondarenko, Larysa B; Matvienko, Anatoliy V; Kovalenko, Valentina M

    2014-09-01

    There is good evidence for impairment of spermatogenesis and reductions in sperm counts and testosterone levels in chronic alcoholics. The mechanisms for these effects have not yet been studied in detail. The consequences of chronic alcohol consumption on the structure and/or metabolism of testis cell macromolecules require to be intensively investigated. The present work reports the effects of chronic alcoholism on contents of free amino acids, levels of cytochrome P450 3A2 (CYP3A2) mRNA expression and DNA fragmentation, as well as on contents of different cholesterol fractions and protein thiol groups in rat testes. Wistar albino male rats were divided into two groups: I - control (intact animals), II - chronic alcoholism (15% ethanol self-administration during 150 days). Following 150 days of alcohol consumption, testicular free amino acid content was found to be significantly changed as compared with control. The most profound changes were registered for contents of lysine (-53%) and methionine (+133%). The intensity of DNA fragmentation in alcohol-treated rat testes was considerably increased, on the contrary CYP3A2 mRNA expression in testis cells was inhibited, testicular contents of total and etherified cholesterol increased by 25% and 45% respectively, and protein SH-groups decreased by 13%. Multidirectional changes of the activities of testicular dehydrogenases were detected. We thus obtained complex assessment of chronic alcoholism effects in male gonads, affecting especially amino acid, protein, ATP and NADPH metabolism. Our results demonstrated profound changes in testes on the level of proteome and genome. We suggest that the revealed metabolic disorders can have negative implication on cellular regulation of spermatogenesis under long-term ethanol exposure.

  15. Commentary: Potential Neurobiologic Mechanisms through Which Metabolic Disorders Could Relate to Autism.

    ERIC Educational Resources Information Center

    Johnston, Michael V.

    2000-01-01

    To illustrate the possible relationships between metabolic disorders and autism, this commentary reviews findings from studies on the characteristics of individuals with Rett syndrome that indicate the genetic mechanism of transcriptional dysregulation can produce pathologic phenotypes which resemble metabolic disorders that stunt axonodendritic…

  16. Noninvasive metabolic profiling for painless diagnosis of human diseases and disorders.

    PubMed

    Mal, Mainak

    2016-06-01

    Metabolic profiling provides a powerful diagnostic tool complementary to genomics and proteomics. The pain, discomfort and probable iatrogenic injury associated with invasive or minimally invasive diagnostic methods, render them unsuitable in terms of patient compliance and participation. Metabolic profiling of biomatrices like urine, breath, saliva, sweat and feces, which can be collected in a painless manner, could be used for noninvasive diagnosis. This review article covers the noninvasive metabolic profiling studies that have exhibited diagnostic potential for diseases and disorders. Their potential applications are evident in different forms of cancer, metabolic disorders, infectious diseases, neurodegenerative disorders, rheumatic diseases and pulmonary diseases. Large scale clinical validation of such diagnostic methods is necessary in future.

  17. Calcium Metabolism in Newborn Infants THE INTERRELATIONSHIP OF PARATHYROID FUNCTION AND CALCIUM, MAGNESIUM, AND PHOSPHORUS METABOLISM IN NORMAL, “SICK,” AND HYPOCALCEMIC NEWBORNS

    PubMed Central

    David, Louis; Anast, Constantine S.

    1974-01-01

    Serum immunoreactive parathyroid hormone (iPTH) and plasma total calcium, ionized calcium, magnesium, and phosphorus levels were determined during the first 9 days of life in 137 normal term infants, 55 “sick” infants, and 43 hypocalcemic (Ca <7.5 mg/100 ml; Ca++<4.0 mg/100 ml) infants. In the cord blood, elevated levels of plasma Ca++ and Ca were observed, while levels of serum iPTH were either undetectable or low. In normal newborns during the first 48 h of life there was a decrease in plasma Ca and Ca++, while the serum iPTH level in most samples remained undetectable or low; after 48 h there were parallel increases in plasma Ca and Ca++ and serum iPTH levels. Plasma Mg and P levels increased progressively after birth in normal infants. In the sick infants, plasma Ca, Ca++ and P levels were significantly lower than in the normal newborns, while no significant differences were found in the plasma Mg levels. The general pattern of serum iPTH levels in the sick infants was similar to that observed in the normal group, though there was a tendency for the increase in serum iPTH to occur earlier and for the iPTH levels to be higher in the sick infants. In the hypocalcemic infants, plasma Mg levels were consistently lower than in the normal infants after 24 h of age, while no significant differences were found in the plasma P levels. Hyperphosphatemia was uncommon and did not appear to be a contributing factor in the pathogenesis of hypocalcemia in most infants. Most of the hypocalcemic infants, including those older than 48 h, had inappropriately low serum iPTH levels. Evidence obtained from these studies indicates that parathyroid secretion is normally low in the early new born period and impaired parathyroid function, characterized by undetectable or low serum iPTH, is present in most infants with neonatal hypocalcemia. Additional unknown factors appear to contribute to the lowering of plasma Ca in the neonatal period. The net effect of unknown plasma

  18. Metabolic Derangement in Acute and Chronic Liver Disorders.

    PubMed

    Bajaj, Sarita; Kashyap, Richi; Srivastava, Anubha; Singh, Smriti

    2017-01-01

    This study aims to assess glycemic and lipid derangement in acute and chronic liver disorders. A cross-sectional study was conducted on 104 patients diagnosed with acute or chronic liver disorder. Acute liver disease (ALD) patients were 40 and chronic liver disease (CLD) patients were 64. The mean value of fasting plasma glucose (FPG) in patients with ALD was 91.8 ± 5.4 mg/dl and in CLD was 115.7 ± 17.9 mg/dl, the difference was significant. The mean value of A1c was 4.3 ± 0.6 in ALD and 6.1 ± 0.8 in CLD, the difference was significant. In patients with CLD mean cholesterol was higher 177.4 ± 28.8 mg/dl when compared to ALD 140 ± 35.1 mg/dl, but the difference was not significant. ALD patients' high-density lipoprotein (HDL) was 50.4 ± 5.1 mg/dl, and in CLD patients, HDL was 44.4 ± 6.1 mg/dl. In CLD mean triglyceride (T) was 148.9 ± 6.4 mg/dl while in ALD T was 134.8 ± 14.2 mg/dl, the difference was significant. CLD is associated with glycemic derangement demonstrated by deranged FPG and A1c. In patients of ALD, no metabolic derangement was observed.

  19. Structural properties of the intrinsically disordered, multiple calcium ion-binding otolith matrix macromolecule-64 (OMM-64).

    PubMed

    Poznar, Monika; Hołubowicz, Rafał; Wojtas, Magdalena; Gapiński, Jacek; Banachowicz, Ewa; Patkowski, Adam; Ożyhar, Andrzej; Dobryszycki, Piotr

    2017-11-01

    Fish otoliths are calcium carbonate biominerals that are involved in hearing and balance sensing. An organic matrix plays a crucial role in their formation. Otolith matrix macromolecule-64 (OMM-64) is a highly acidic, calcium-binding protein (CBP) found in rainbow trout otoliths. It is a component of high-molecular-weight aggregates, which influence the size, shape and polymorph of calcium carbonate in vitro. In this study, a protocol for the efficient expression and purification of OMM-64 was developed. For the first time, the complete structural characteristics of OMM-64 were described. Various biophysical methods were combined to show that OMM-64 occurs as an intrinsically disordered monomer. Under denaturing conditions (pH, temperature) OMM-64 exhibits folding propensity. It was determined that OMM-64 binds approximately 61 calcium ions with millimolar affinity. The folding-unfolding experiments showed that calcium ions induced the collapse of OMM-64. The effect of other counter ions present in trout endolymph on OMM-64 conformational changes was studied. The significance of disordered properties of OMM-64 and the possible function of this protein is discussed. Copyright © 2017 Elsevier B.V. All rights reserved.

  20. Regulation of the reserve carbohydrate metabolism by alkaline pH and calcium in Neurospora crassa reveals a possible cross-regulation of both signaling pathways.

    PubMed

    Virgilio, Stela; Cupertino, Fernanda Barbosa; Ambrosio, Daniela Luz; Bertolini, Maria Célia

    2017-06-09

    Glycogen and trehalose are storage carbohydrates and their levels in microorganisms vary according to environmental conditions. In Neurospora crassa, alkaline pH stress highly influences glycogen levels, and in Saccharomyces cerevisiae, the response to pH stress also involves the calcineurin signaling pathway mediated by the Crz1 transcription factor. Recently, in yeast, pH stress response genes were identified as targets of Crz1 including genes involved in glycogen and trehalose metabolism. In this work, we present evidence that in N. crassa the glycogen and trehalose metabolism is modulated by alkaline pH and calcium stresses. We demonstrated that the pH signaling pathway in N. crassa controls the accumulation of the reserve carbohydrates glycogen and trehalose via the PAC-3 transcription factor, which is the central regulator of the signaling pathway. The protein binds to the promoters of most of the genes encoding enzymes of glycogen and trehalose metabolism and regulates their expression. We also demonstrated that the reserve carbohydrate levels and gene expression are both modulated under calcium stress and that the response to calcium stress may involve the concerted action of PAC-3. Calcium activates growth of the Δpac-3 strain and influences its glycogen and trehalose accumulation. In addition, calcium stress differently regulates glycogen and trehalose metabolism in the mutant strain compared to the wild-type strain. While glycogen levels are decreased in both strains, the trehalose levels are significantly increased in the wild-type strain and not affected by calcium in the mutant strain when compared to mycelium not exposed to calcium. We previously reported the role of PAC-3 as a transcription factor involved in glycogen metabolism regulation by controlling the expression of the gsn gene, which encodes an enzyme of glycogen synthesis. In this work, we extended the investigation by studying in greater detail the effects of pH on the metabolism of the

  1. Physiology of Calcium, Phosphate, Magnesium and Vitamin D.

    PubMed

    Allgrove, Jeremy

    2015-01-01

    The physiology of calcium and the other minerals involved in its metabolism is complex and intimately linked to the physiology of bone. Five principal humoral factors are involved in maintaining plasma concentrations of calcium, magnesium and phosphate and in coordinating the balance between their content in bone. The transmembrane transport of these elements is dependent on a series of complex mechanisms that are partly controlled by these hormones. The plasma concentration of calcium is initially sensed by a calcium-sensing receptor, which then sets up a cascade of events that initially determines parathyroid hormone secretion and eventually results in a specific action within the target organs, mainly bone and kidney. This chapter describes the physiology of these humoral factors and relates them to the pathological processes that give rise to disorders of calcium, phosphate and magnesium metabolism as well as of bone metabolism. This chapter also details the stages in the calcium cascade, describes the effects of calcium on the various target organs, gives details of the processes by which phosphate and magnesium are controlled and summarises the metabolism of vitamin D. The pathology of disorders of bone and calcium metabolism is described in detail in the relevant chapters. © 2015 S. Karger AG, Basel.

  2. Changes in Hematology and Calcium Metabolism After Gastric Bypass Surgery--a 2-Year Follow-Up Study.

    PubMed

    Worm, Dorte; Madsbad, Sten; Kristiansen, Viggo B; Naver, Lars; Hansen, Dorte Lindqvist

    2015-09-01

    Concerns regarding nutritional deficiencies have recently emerged after Roux-en-Y gastric bypass (RYGB). A total of 835 subjects underwent RYGB, age 43.3 years, body mass index (BMI) 47.2 kg/m(2). Hematological and calcium metabolic variables were measured before, 6, 12, and 24 months after surgery. Daily supplement of 800 mg calcium, 800 U vitamin D, a multivitamin, and a vitamin B12 injection (1 mg) every third month was recommended. In subjects with low ferritin and decreasing hemoglobin levels, oral, or intravenous iron was administered. Hemoglobin concentration decreased from before surgery to month 24 for both men (9.3 ± 0.05 vs. 8.3 ± 0.08 mmol/L, p < 0.001) and women (8.4 ± 0.03 vs. 7.7 ± 0.06 mmol/L, p < 0.001). At 24 months, anemia was present in 25.8 % of women and 22.1 % of men. Predictors of anemia in both sexes were baseline hemoglobin (p < 0.001), excessive weight loss in men, and younger age in women (p < 0.001). Plasma ferritin levels decreased in both sexes (p < 0.01), whereas concentrations of folic acid and vitamin B12 increased from before surgery to 24 months after surgery (p < 0.001). Vitamin D increased from baseline to month 24 in both sexes (p < 0.01). In women, PTH increased from baseline to month 24 (p < 0.05) with no changes in calcium or magnesium. Supplementation of calcium and vitamin D was sufficient. Iron substitution did not prevent anemia, which especially affected premenopausal women. More attention should be given to iron substitution after RYGB.

  3. 25-Hydroxycholecalciferol as an antagonist of adverse corticosteroid effects on phosphate and calcium metabolism in man.

    PubMed

    Nuti, R; Vattimo, A; Turchetti, V; Righi, G

    1984-10-01

    The present study was performed in 30 patients who needed steroid therapy: courses of triamcinolone or DTM 8-15 given orally lasted 30 days. In 15 of these patients glucoactive corticosteroids were administered in combination with 5 micrograms/day of 25OH-vitamin D3 (25OHD3). 47Calcium oral test and 99mTc-MDP kinetics, as an index of bone turnover, were performed at the beginning of the therapy and after 30 days. At the end of treatment a significant improvement of intestinal radiocalcium transport together with a decrease in bone turnover in the group of patients treated with 25OHD3 was observed. As it concerns plasma calcium level, inorganic phosphate, the urinary excretion of calcium, phosphate and hydroxyproline no significant difference between the two groups examined were noticed. These results indicate that the adverse effects of glucoactive corticosteroids on intestinal calcium transport and bone turnover may be counteracted by the combined administration of physiological doses of 25OHD3.

  4. Calcium homeostasis and bone metabolic responses to protein diets and energy restriction: a randomized control trial

    USDA-ARS?s Scientific Manuscript database

    Despite some beneficial effects on bone, high protein diets are conventionally considered a primary dietary risk factor for osteoporosis and bone fracture due to the acid load associated with protein catabolism. To test the hypothesis that high dietary protein diets do not negatively affect calcium ...

  5. The Role of Nutrition in the Changes in Bone and Calcium Metabolism During Space Flight

    NASA Technical Reports Server (NTRS)

    Morey-Holton, Emily R.; Arnaud, Sara B.

    1995-01-01

    On Earth, the primary purpose of the skeleton is provide structural support for the body. In space, the support function of the skeleton is reduced since, without gravity, structures have only mass and no weight. The adaptation to space flight is manifested by shifts in mineral distribution, altered bone turnover, and regional mineral deficits in weight-bearing bones. The shifts in mineral distribution appear to be related to the cephalic fluid shift. The redistribution of mineral from one bone to another or to and from areas in the same bone in response to alterations in gravitational loads is more likely to affect skeletal function than quantitative whole body losses and gains. The changes in bone turnover appear dependent upon changes in body weight with weight loss tending to increase bone resorption as well as decrease bone formation. During bedrest, the bone response to unloading varies depending upon the routine activity level of the subjects with more active subjects showing a greater suppression of bone formation in the iliac crest with inactivity. Changes in body composition during space flight are predicted by bedrest studies on Earth which show loss of lean body mass and increase tn body fat in adult males after one month. In ambulatory studies on Earth, exercising adult males of the same age, height, g weight, body mass index, and shoe size show significantly higher whole body mineral and lean body mass. than non-exercising subjects. Nutritional preference appears to change with activity level. Diet histories in exercisers and nonexercisers who maintain identical body weights show no differences in nutrients except for slightly higher carbohydrate intake in the exercisers. The absence of differences in dietary calcium in men with higher total body calcium is noteworthy. In this situation, the increased bone mineral content was facilitated by the calcium endocrine system. This regulatory system can be by-passed by raising dietary calcium. Increased

  6. Relation of periodontitis and metabolic syndrome with gestational glucose metabolism disorder.

    PubMed

    Bullon, Pedro; Jaramillo, Reyes; Santos-Garcia, Rocio; Rios-Santos, Vicente; Ramirez, Maria; Fernandez-Palacin, Ana; Fernandez-Riejos, Patricia

    2014-02-01

    Gestational diabetes mellitus (GDM) and metabolic syndrome have been related to periodontitis. This study's objective is to establish the relationship between them in pregnant women affected by gestational glucose metabolism disorder. In 188 pregnant women with positive O'Sullivan test (POT) results, an oral glucose tolerance test (OGTT) was performed to diagnose GDM. The mother's periodontal parameters, age, prepregnancy weight and height and body mass index (BMI), blood pressure, gestational age, and birth weight were recorded at 24 to 28 weeks of pregnancy, as well as levels of glucose, C-reactive protein, triglycerides, glycated hemoglobin (HbA1c), and total, low-density lipoprotein, high-density lipoprotein (HDL), and very-low-density lipoprotein (VLDL) cholesterol levels. Prepregnancy weight, prepregnancy BMI, systolic and diastolic blood pressure, VLDL cholesterol, and glucose parameters were higher in GDM compared with POT (P <0.05). VLDL cholesterol, triglycerides, and 2-hour OGTT were higher in patients with periodontitis than in patients without periodontitis (P <0.05). HbA1c, triglycerides, and 1- and 2-hour OGTT were positively related with probing depth and clinical attachment level; blood glucose was related only to bleeding on probing (P <0.05). HbA1c, basal OGTT, and 1- and 2-hour OGTT were positively related to prepregnancy BMI and blood pressure; HDL cholesterol was negatively related to prepregnancy BMI; C-reactive protein was positively related to prepregnancy BMI and diastolic blood pressure (P <0.05). These data support the relationships among periodontal disease and some biochemical parameters such as lipid and glucose data in pregnancy, and also among metabolic syndrome and biochemical parameters.

  7. Calcium and vitamin D supplementation through fortified dairy products counterbalances seasonal variations of bone metabolism indices: the Postmenopausal Health Study.

    PubMed

    Tenta, Roxane; Moschonis, George; Koutsilieris, Michael; Manios, Yannis

    2011-08-01

    To assess the effectiveness of a dietary intervention combined with fortified dairy products on bone metabolism and bone mass indices in postmenopausal women. Forty postmenopausal women (55-65 years old) were equally randomized into a dietary group (DG), receiving daily and for 30 months, 1,200 mg of calcium and 7.5 μg of vitamin D(3) for the first 12 months that increased to 22.5 μg for the remaining 18 months of intervention through fortified dairy products; and a control group (CG). Differences in the changes of bone metabolism and bone mass indices were examined with repeated measures ANOVA. A significant increase was observed for PTH levels only in the CG during the first six winter months of intervention (p = 0.049). After 30 months of intervention, during winter, serum 25(OH)D significantly decreased in the CG while remained in the same high levels as in the summer period in the DG. Serum RANKL levels decreased significantly in the DG compared with the increase in the CG during the 30-month intervention period (p = 0.005). Serum CTx decreased significantly in the DG after six (-0.08; -0.12 to -0.03) and 12 (-0.03; -0.08 to -0.02) months of intervention. Finally, the DG had more favorable changes in total body BMD than the CG (p < 0.001). Increasing dietary intake of calcium and vitamin D in osteopenic postmenopausal women appears to be effective in producing favorable changes in several bone metabolism and bone mass indices and in counterbalancing seasonal variations in hormonal and biochemical molecules.

  8. Metabolism and insulin signaling in common metabolic disorders and inherited insulin resistance.

    PubMed

    Højlund, Kurt

    2014-07-01

    Type 2 diabetes, obesity and polycystic ovary syndrome (PCOS) are common metabolic disorders which are observed with increasing prevalences, and which are caused by a complex interplay between genetic and environmental factors, including increased calorie intake and physical inactivity. These metabolic disorders are all characterized by reduced plasma adiponectin and insulin resistance in peripheral tissues. Quantitatively skeletal muscle is the major site of insulin resistance. Both low plasma adiponectin and insulin resistance contribute to an increased risk of type 2 diabetes and cardiovascular disease. In several studies, we have investigated insulin action on glucose and lipid metabolism, and at the molecular level, insulin signaling to glucose transport and glycogen synthesis in skeletal muscle from healthy individuals and in obesity, PCOS and type 2 diabetes. Moreover, we have described a novel syndrome characterized by postprandial hyperinsulinemic hypoglycemia and insulin resistance. This syndrome is caused by a mutation in the tyrosine kinase domain of the insulin receptor gene (INSR). We have studied individuals with this mutation as a model of inherited insulin resistance. Type 2 diabetes, obesity and PCOS are characterized by pronounced defects in the insulin-stimulated glucose uptake, in particular glycogen synthesis and to a lesser extent glucose oxidation, and the ability of insulin to suppress lipid oxidation. In inherited insulin resistance, however, only insulin action on glucose uptake and glycogen synthesis is impaired. This suggests that the defects in glucose and lipid oxidation in the common metabolic disorders are secondary to other factors. In young women with PCOS, the degree of insulin resistance was similar to that seen in middle-aged patients with type 2 diabetes. This supports the hypothesis of an unique pathogenesis of insulin resistance in PCOS. Insulin in physiological concentrations stimulates glucose uptake in human skeletal

  9. Case report: a metabolic disorder presenting as pediatric manganism.

    PubMed

    Sahni, Vanita; Léger, Yves; Panaro, Linda; Allen, Mark; Giffin, Scott; Fury, Diane; Hamm, Nadine

    2007-12-01

    Manganese is a trace element, essential for physiologic functioning but neurotoxic at high doses. Common exposure sources include dietary intake as well as drinking water in some regions; toxicity is most often associated with inhalation exposures in occupational settings. In this article we describe the investigation of a pediatric case of manganism using both clinical and environmental assessment methods. A previously healthy 6-year-old child presented with severe Mn neurotoxicity, iron deficiency, and elevated cobalt levels. Immediate and selected extended family members had elevated plasma Mn but remained asymptomatic. An exposure assessment identified seasonal ingestion exposures to Mn at the family's summer cottage; these were common to the four immediate family members. Well water used for drinking and cooking exceeded recommended guidelines, and foods high in Mn predominated in their diet. No inhalation exposures were identified. Only pica was unique to the patient. The combined evidence of the environmental assessment and biomonitoring of blood Mn levels supported a seasonal ingestion exposure source; this alone was insufficient to explain the toxicity because the patient's 7-year-old sibling was asymptomatic with almost identical exposures (except pica). A metabolic disorder involving divalent metals (Mn, Fe, and Co) interacting with environmental exposures is the most likely explanation. This case report adds to the emerging body of evidence linking neurologic effects to ingestion Mn exposure.

  10. [Homocysteine metabolism disorders as a potential predictor of preeclamsia].

    PubMed

    Kajdy, Anna; Niemiec, Tomasz

    2008-11-01

    Preeclampsia is one of the main causes of maternal and fetal mortality. We lack a reliable test that would identify the "at risk" group of pregnant women, thus allowing us to implement a specific prevention, management and treatment program. Recently, a number of theories regarding the pathophysiology of preeclampsia has been published. The role of vascular pathology as a result of an increase in homocysteine level is often mentioned. The aim of this paper is to review the current literature related to the pathology of preeclampsia and to evaluate the usefulness of assessment of homocysteine level and homocysteine metabolism disorders as a potential predictor of preeclamsia. Hiperhomocysteinemia is a known risk factor of cardiovascular diseases and hypertension. Different sources report a similar correlation between an increase in homocysteine level and the incidence of preeclampsia. As far as the topic of homocysteine in pregnancy is concerned, numerous questions and problems remain unanswered and unsolved. Although there exists a relationship between an increased values of homocysteine and the incidence of preeclampsia, there is not enough information about what group of patients should be included in the screening test to increase the rate of diagnosis and prevention of the most dangerous sequele.

  11. Newborn screening of metabolic disorders: recent progress and future developments.

    PubMed

    Rinaldo, Piero; Lim, James S; Tortorelli, Silvia; Gavrilov, Dimitar; Matern, Dietrich

    2008-01-01

    Tandem mass spectrometry has been the main driver behind a significant expansion in newborn screening programs. The ability to detect more than 40 conditions by a single test underscores the need to better understand the clinical and laboratory characteristics of the conditions being tested, and the complexity of pattern recognition and differential diagnoses of one or more elevated markers. The panel of conditions recommended by the American College of Medical Genetics, including 20 primary conditions and 22 secondary targets that are detectable by tandem mass spectrometry has been adopted as the standard of care in the vast majority of US states. The evolution of newborn screening is far from being idle as a large number of infectious, genetic, and metabolic conditions are currently under investigation at variable stages of test development and clinical validation. In the US, a formal process with oversight by the Advisory Committee on Heritable Disorders and Genetic Diseases in Newborns and Children has been established for nomination and evidence-based review of new candidate conditions. If approved, these conditions could be added to the uniform panel and consequently pave the way to large scale implementation.

  12. Use of rumination and activity monitoring for the identification of dairy cows with health disorders: Part I. Metabolic and digestive disorders.

    PubMed

    Stangaferro, M L; Wijma, R; Caixeta, L S; Al-Abri, M A; Giordano, J O

    2016-09-01

    The objectives of this study were to evaluate (1) the performance of an automated health-monitoring system (AHMS) to identify cows with metabolic and digestive disorders-including displaced abomasum, ketosis, and indigestion-based on an alert system (health index score, HIS) that combines rumination time and physical activity; (2) the number of days between the first HIS alert and clinical diagnosis (CD) of the disorders by farm personnel; and (3) the daily rumination time, physical activity, and HIS patterns around CD. Holstein cattle (n=1,121; 451 nulliparous and 670 multiparous) were fitted with a neck-mounted electronic rumination and activity monitoring tag (HR Tags, SCR Dairy, Netanya, Israel) from at least -21 to 80 d in milk (DIM). Raw data collected in 2-h periods were summarized per 24 h as daily rumination and activity. A HIS (0 to 100 arbitrary units) was calculated daily for individual cows with an algorithm that used rumination and activity. A positive HIS outcome was defined as a HIS of <86 during at least 1 d from -5 to 2 d after CD. Blood concentrations of nonesterified fatty acids, β-hydroxybutyrate, total calcium, and haptoglobin were determined in a subgroup of cows (n=459) at -11±3, -4±3, 0, 3±1, 7±1, 14±1, and 28±1 DIM. The sensitivity of the HIS was 98% [95% confidence interval (CI): 93, 100] for displaced abomasum (n=41); 91% (95% CI: 83, 99) for ketosis (n=54); 89% (95% CI: 68, 100) for indigestion (n=9); and 93% (95% CI: 89, 98) for all metabolic and digestive disorders combined (n=104). Days (mean and 95% CI) from the first positive HIS <86 and CD were -3 (-3.7, -2.3), -1.6 (-2.3, -1.0), -0.5 (-1.5, 0.5), and -2.1 (-2.5, -1.6) for displaced abomasum, ketosis, indigestion, and all metabolic and digestive disorders, respectively. The patterns of rumination, activity, and HIS for cows flagged by the AHMS were characterized by lower levels than for cows without a health disorder and cows not flagged by the AHMS from -5 to 5 d after CD

  13. The control of calcium metabolism by parathyroid hormone, calcitonin and vitamin D

    NASA Technical Reports Server (NTRS)

    Potts, J. T., Jr.

    1976-01-01

    Advances in analysis of chemistry and physiology of parathyroid hormone, calcitonin, and Vitamin D are described along with development of techniques in radioassay methods. Emphasis is placed on assessment of normal and abnormal patterns of secretion of these hormones in specific relation to the physiological adaptations of weightlessness and space flight. Related diseases that involve perturbations in normal skeletal and calcium homeostasis are also considered.

  14. The effects of UV light on calcium metabolism in ball pythons (Python regius).

    PubMed

    Hedley, J; Eatwell, K

    2013-10-12

    Despite the popularity of keeping snakes in captivity, there has been limited investigation into the effects of UV radiation on vitamin D levels in snakes. The aim of this study was to investigate the effects of UV-b radiation on plasma 25-hydroxyvitamin D3 levels and ionised calcium concentrations in ball pythons (Python regius). Blood samples were taken from 14 ball pythons, which had never been exposed to UV-b light, to obtain baseline 25-hydroxyvitamin D3 levels and ionised calcium concentrations. Blood samples were then taken again from the same snakes 70 days later after one group (Group 1, n=6 females) were exposed to UV-b radiation daily, and the other group (Group 2, n=5 males and 3 females) were exposed to no UV-b radiation. Mean±sd 25-hydroxyvitamin D3 levels on day 0 in Group 1 were 197±35 nmol/l, and on day 70 were 203.5±13.8 nmol/l. Mean±sd 25-hydroxyvitamin D3 levels in Group 2 on day 0 were 77.7±41.5 nmol/l, and on day 70 were 83.0±41.9 nmol/l. Mean±sd ionised calcium levels at day 0 were 1.84±0.05 mmol/l for Group 1, and on day 70 were 1.78±0.07 mmol/l. Mean±sd ionised calcium levels at day 0 were 1.79±0.07 mmol/l for Group 2, and on day 70 were 1.81±0.05 mmol/l. No association was demonstrated between exposure to UV-b radiation and plasma 25-hydroxyvitamin D3 and ionised calcium concentrations. These results may provide baseline parameters for future studies in this and other snake species to determine ability to utilise UV-b light for vitamin D production.

  15. Increased white matter metabolic rates in autism spectrum disorder and schizophrenia.

    PubMed

    Mitelman, Serge A; Buchsbaum, Monte S; Young, Derek S; Haznedar, M Mehmet; Hollander, Eric; Shihabuddin, Lina; Hazlett, Erin A; Bralet, Marie-Cecile

    2017-11-22

    Both autism spectrum disorder (ASD) and schizophrenia are often characterized as disorders of white matter integrity. Multimodal investigations have reported elevated metabolic rates, cerebral perfusion and basal activity in various white matter regions in schizophrenia, but none of these functions has previously been studied in ASD. We used 18 fluorodeoxyglucose positron emission tomography to compare white matter metabolic rates in subjects with ASD (n = 25) to those with schizophrenia (n = 41) and healthy controls (n = 55) across a wide range of stereotaxically placed regions-of-interest. Both subjects with ASD and schizophrenia showed increased metabolic rates across the white matter regions assessed, including internal capsule, corpus callosum, and white matter in the frontal and temporal lobes. These increases were more pronounced, more widespread and more asymmetrical in subjects with ASD than in those with schizophrenia. The highest metabolic increases in both disorders were seen in the prefrontal white matter and anterior limb of the internal capsule. Compared to normal controls, differences in gray matter metabolism were less prominent and differences in adjacent white matter metabolism were more prominent in subjects with ASD than in those with schizophrenia. Autism spectrum disorder and schizophrenia are associated with heightened metabolic activity throughout the white matter. Unlike in the gray matter, the vector of white matter metabolic abnormalities appears to be similar in ASD and schizophrenia, may reflect inefficient functional connectivity with compensatory hypermetabolism, and may be a common feature of neurodevelopmental disorders.

  16. Bifidobacteria attenuate the development of metabolic disorders, with inter- and intra-species differences.

    PubMed

    Zhu, Guangsu; Ma, Fangli; Wang, Gang; Wang, Yuanyuan; Zhao, Jianxin; Zhang, Hao; Chen, Wei

    2018-06-20

    Host gut microbiota dysbiosis occurs for multiple reasons and is often accompanied by chronic inflammation induced by a high-fat-high-sucrose (HFHS) diet and related metabolic disorders. Intervention with probiotics is a novel strategy for amelioration of metabolic syndrome, which is believed to regulate the gut microbiota composition to some extent. We investigated the relationship amongst bifidobacteria treatment, HFHS diet-induced metabolic disorders and the gut microbiota composition. Seven strains of bifidobacteria from four species were individually administered to rats fed a HFHS diet for 12 weeks. Various bifidobacteria strains showed various effects on the recovery of metabolic disorders and gut microbiota dysbiosis, and these effects seemed to be inter- or intra-species specific. Bifidobacterium longum, B. adolescentis and B. bifidum seemed to affect the blood glucose balance, whilst two strains of B. breve showed extremely different effects in this area. However, only one strain of B. longum and the B. adolescentis displayed significant regulation of blood lipid levels. The protective effects of bifidobacteria on the pancreas were strongly correlated with those on blood glucose. Furthermore, the influence of bifidobacteria on gut microbiota dysbiosis also showed a potential relationship with symptoms of metabolic disorders. Of these seven strains, B. adolescentis Z25 displayed an outstanding ability to alleviate metabolic syndrome, including glucose and lipid metabolism disorders, tissue damage and gut microbiota dysbiosis. This strain, coupled with other prebiotics and probiotics, could be used as a potential treatment approach for metabolic syndrome induced by a HFHS diet.

  17. MT2013-31: Allo HCT for Metabolic Disorders and Severe Osteopetrosis

    ClinicalTrials.gov

    2018-01-19

    Mucopolysaccharidosis Disorders; Hurler Syndrome; Hunter Syndrome; Maroteaux Lamy Syndrome; Sly Syndrome; Alpha-Mannosidosis; Fucosidosis; Aspartylglucosaminuria; Glycoprotein Metabolic Disorders; Sphingolipidoses; Recessive Leukodystrophies; Globoid Cell Leukodystrophy; Metachromatic Leukodystrophy; Niemann-Pick B; Niemann-Pick C Subtype 2; Sphingomyelin Deficiency; Peroxisomal Disorders; Adrenoleukodystrophy With Cerebral Involvement; Zellweger Syndrome; Neonatal Adrenoleukodystrophy; Infantile Refsum Disease; Acyl-CoA Oxidase Deficiency; D-Bifunctional Enzyme Deficiency; Multifunctional Enzyme Deficiency; Alpha-methylacyl-CoA Racmase Deficiency; Mitochondrial Neurogastrointestingal Encephalopathy; Severe Osteopetrosis; Hereditary Leukoencephalopathy With Axonal Spheroids (HDLS; CSF1R Mutation); Inherited Metabolic Disorders

  18. Effects of dietary omega-3 on dystrophic cardiac and diaphragm muscles as evaluated by 1H magnetic resonance spectroscopy: Metabolic profile and calcium-related proteins.

    PubMed

    Maurício, Adriana Fogagnolo; de Carvalho, Samara Camaçari; Santo Neto, Humberto; Marques, Maria Julia

    2017-08-01

    Duchenne muscular dystrophy (DMD) is characterized by the absence of dystrophin and muscle degeneration. Calcium dysregulation and oxidative stress also contribute to the disease progression. We evaluated the potential therapeutic benefits of supplementation with omega-3 on the metabolic profile, calcium-related proteins and oxidative stress response in the heart and diaphragm (DIA) of the mdx mouse model of DMD at later stages of the disease (13 months). Mdx mice (8 months old) received omega-3 via a dietary supplement for 5 months. Metabolites were analyzed by 1 H magnetic resonance spectroscopy. Muscle total calcium was evaluated by inductively coupled plasma-optical emission spectrometry. Calsequestrin, TRPC1 and 4-HNE were determined via Western blot. Omega-3 decreased the metabolites taurine (related to calcium regulation and oxidative stress), aspartate (related to inflammation) and oxypurinol (related to oxidative stress) in the heart (aspartate) and DIA (taurine, aspartate and oxypurinol). Omega-3 also significantly decreased total calcium and TRPC1 levels in cardiac and DIA muscles and increased the levels of calsequestrin (cardiac and skeletal) and decreased the oxidative stress marker 4-HNE. The current study suggests that supplementation with omega-3 may generate therapeutic benefits on dystrophy progression, at later stages of the disease, with changes in the metabolic profile that may be correlated to omega-3 therapy. Copyright © 2017 European Society for Clinical Nutrition and Metabolism. Published by Elsevier Ltd. All rights reserved.

  19. Emerging Drugs and Indications for Cardio-Metabolic Disorders in People with Severe Mental Illness.

    PubMed

    Kouidrat, Youssef; Amad, Ali; De Hert, Marc

    2015-01-01

    Patients with severe mental illnesses, such as schizophrenia and bipolar disorder, are at increased risk of developing metabolic disorders including obesity, diabetes, and dyslipidemia. All of these comorbidities increase the risk of cardiovascular disease and mortality. Different approaches, including diet and lifestyle modifications, behavioral therapy and switching antipsychotic agents, have been proposed to manage these metabolic abnormalities. However, these interventions may be insufficient, impractical or fail to counteract the metabolic dysregulation. Consequently, a variety of pharmacological agents such as antidiabetic drugs, have been studied in an attempt to reverse the weight gain and metabolic abnormalities evident in these patients. Despite a significant effect, many of these treatments are used off-label. This qualitative review focuses on pharmacological agents that could offer significant benefits in the management of cardio-metabolic disorders associated with serious mental illness.

  20. Alpha-synuclein, epigenetics, mitochondria, metabolism, calcium traffic, & circadian dysfunction in Parkinson's disease. An integrated strategy for management.

    PubMed

    Phillipson, Oliver T

    2017-11-01

    The motor deficits which characterise the sporadic form of Parkinson's disease arise from age-related loss of a subset of dopamine neurons in the substantia nigra. Although motor symptoms respond to dopamine replacement therapies, the underlying disease process remains. This review details some features of the progressive molecular pathology and proposes deployment of a combination of nutrients: R-lipoic acid, acetyl-l-carnitine, ubiquinol, melatonin (or receptor agonists) and vitamin D3, with the collective potential to slow progression of these features. The main nutrient targets include impaired mitochondria and the associated oxidative/nitrosative stress, calcium stress and impaired gene transcription induced by pathogenic forms of alpha- synuclein. Benefits may be achieved via nutrient influence on epigenetic signaling pathways governing transcription factors for mitochondrial biogenesis, antioxidant defences and the autophagy-lysosomal pathway, via regulation of the metabolic energy sensor AMP activated protein kinase (AMPK) and the mammalian target of rapamycin mTOR. Nutrients also benefit expression of the transcription factor for neuronal survival (NR4A2), trophic factors GDNF and BDNF, and age-related calcium signals. In addition a number of non-motor related dysfunctions in circadian control, clock genes and associated metabolic, endocrine and sleep-wake activity are briefly addressed, as are late-stage complications in respect of cognitive decline and osteoporosis. Analysis of the network of nutrient effects reveals how beneficial synergies may counter the accumulation and promote clearance of pathogenic alpha-synuclein. Crown Copyright © 2017. Published by Elsevier B.V. All rights reserved.

  1. Longitudinal Associations between Posttraumatic Stress Disorder and Metabolic Syndrome Severity

    PubMed Central

    Wolf, Erika J.; Bovin, Michelle J.; Green, Jonathan D.; Mitchell, Karen S.; Stoop, Tawni B.; Barretto, Kenneth M.; Jackson, Colleen E.; Lee, Lewina O.; Fang, Shona C.; Trachtenberg, Felicia; Rosen, Raymond C.; Keane, Terence M.; Marx, Brian P.

    2016-01-01

    Background Posttraumatic stress disorder (PTSD) is associated with elevated risk for metabolic syndrome (MetS). However, the direction of this association is not yet established, as most prior studies employed cross-sectional designs. The primary goal of this study was to evaluate bidirectional associations between PTSD and MetS using a longitudinal design. Methods 1,355 male and female veterans of the conflicts in Iraq and Afghanistan underwent PTSD diagnostic assessments and their biometric profiles pertaining to MetS were extracted from the electronic medical record at two time points (spanning ~2.5 years, n = 971 at time 2). Results The prevalence of MetS among veterans with PTSD was just under 40% at both time points and was significantly greater than that for veterans without PTSD; the prevalence of MetS among those with PTSD was also elevated relative to age-matched population estimates. Cross-lagged panel models revealed that PTSD severity predicted subsequent increases in MetS severity (β = .08, p = .002), after controlling for initial MetS severity, but MetS did not predict later PTSD symptoms. Logistic regression results suggested that for every 10 PTSD symptoms endorsed at time 1, the odds of a subsequent MetS diagnosis increased by 56%. Conclusions Results highlight the substantial cardiometabolic concerns of young veterans with PTSD and raise the possibility that PTSD may predispose individuals to accelerated aging, in part, manifested clinically as MetS. This demonstrates the need to identify those with PTSD at greatest risk for MetS and to develop interventions that improve both conditions. PMID:27087657

  2. Relationship of metabolic syndrome with incident aortic valve calcium and aortic valve calcium progression: the Multi-Ethnic Study of Atherosclerosis (MESA).

    PubMed

    Katz, Ronit; Budoff, Matthew J; Takasu, Junichiro; Shavelle, David M; Bertoni, Alain; Blumenthal, Roger S; Ouyang, Pamela; Wong, Nathan D; O'Brien, Kevin D

    2009-04-01

    Metabolic syndrome (MetS) has been associated with increased prevalence of aortic valve calcium (AVC) and with increased progression of aortic stenosis. The purpose of this study was to determine whether MetS is associated with increased risks for the development of new ("incident") AVC or for progression of established AVC as assessed by CT. The relationships of MetS or its components as well as of diabetes to risks for incident AVC or AVC progression were studied among participants with CT scans performed at baseline and at either year 2 or year 3 examinations in the Multi-Ethnic Study of Atherosclerosis (MESA). Of 5,723 MESA participants meeting criteria for inclusion, 1,674 had MetS by Adult Treatment Panel III criteria, whereas 761 had diabetes. Among the 5,123 participants without baseline AVC, risks for incident AVC, adjusted for time between scans, age, sex, race/ethnicity, LDL cholesterol, lipid-lowering medications, and smoking, were increased significantly for MetS (odds ratio [OR] 1.67 [95% CI 1.21-2.31]) or diabetes (2.06 [1.39-3.06]). In addition, there was an increase in incident AVC risk with increasing number of MetS components. Similar results were found using the International Diabetes Federation MetS criteria. Among the 600 participants (10.5%) with baseline AVC, neither MetS nor diabetes was associated with AVC progression. In the MESA cohort, MetS was associated with a significant increase in incident ("new") AVC, raising the possibility that MetS may be a potential therapeutic target to prevent AVC development.

  3. Microgravity effects during fertilization, cell division, development, and calcium metabolism in sea urchins

    NASA Technical Reports Server (NTRS)

    Schatten, Heide

    1996-01-01

    The overall objectives of this project are to explore the role of microgravity during fertilization, early development, cytoskeletal organization, and skeletal calcium deposition in a model development system: the sea urchin eggs and embryos. While pursuing these objectives, we have also helped to develop, test, and fly the Aquatic Research Facility (ARF) system. Cells were fixed at preselected time points to preserve the structures and organelles of interest with regards to cell biology events during development. The protocols used for the analysis of the results had been developed during the earlier part of this research and were applied for post-flight analysis using light and (immuno)fluorescence microscopy, scanning electron microscopy, and transmission electron microscopy. The structures of interest are: microtubules during fertilization, cell division, and cilia movement; microfilaments during cell surface restructuring and cell division; centrosomes and centrioles during cell division, cell differentiation, and cilia formation and movement; membranes, Golgi, endoplasmic reticulum, mitochondria, and chromosomes at all stages of development; and calcium deposits during spicule formation in late-stage embryos. In addition to further explore aspects important or living in space, several aspects of this research are also aimed at understanding diseases that affect humans on Earth which may be accelerated in space.

  4. Intrinsically disordered and pliable Starmaker-like protein from medaka (Oryzias latipes) controls the formation of calcium carbonate crystals.

    PubMed

    Różycka, Mirosława; Wojtas, Magdalena; Jakób, Michał; Stigloher, Christian; Grzeszkowiak, Mikołaj; Mazur, Maciej; Ożyhar, Andrzej

    2014-01-01

    Fish otoliths, biominerals composed of calcium carbonate with a small amount of organic matrix, are involved in the functioning of the inner ear. Starmaker (Stm) from zebrafish (Danio rerio) was the first protein found to be capable of controlling the formation of otoliths. Recently, a gene was identified encoding the Starmaker-like (Stm-l) protein from medaka (Oryzias latipes), a putative homologue of Stm and human dentine sialophosphoprotein. Although there is no sequence similarity between Stm-l and Stm, Stm-l was suggested to be involved in the biomineralization of otoliths, as had been observed for Stm even before. The molecular properties and functioning of Stm-l as a putative regulatory protein in otolith formation have not been characterized yet. A comprehensive biochemical and biophysical analysis of recombinant Stm-l, along with in silico examinations, indicated that Stm-l exhibits properties of a coil-like intrinsically disordered protein. Stm-l possesses an elongated and pliable structure that is able to adopt a more ordered and rigid conformation under the influence of different factors. An in vitro assay of the biomineralization activity of Stm-l indicated that Stm-l affected the size, shape and number of calcium carbonate crystals. The functional significance of intrinsically disordered properties of Stm-l and the possible role of this protein in controlling the formation of calcium carbonate crystals is discussed.

  5. Intrinsically Disordered and Pliable Starmaker-Like Protein from Medaka (Oryzias latipes) Controls the Formation of Calcium Carbonate Crystals

    PubMed Central

    Różycka, Mirosława; Wojtas, Magdalena; Jakób, Michał; Stigloher, Christian; Grzeszkowiak, Mikołaj; Mazur, Maciej; Ożyhar, Andrzej

    2014-01-01

    Fish otoliths, biominerals composed of calcium carbonate with a small amount of organic matrix, are involved in the functioning of the inner ear. Starmaker (Stm) from zebrafish (Danio rerio) was the first protein found to be capable of controlling the formation of otoliths. Recently, a gene was identified encoding the Starmaker-like (Stm-l) protein from medaka (Oryzias latipes), a putative homologue of Stm and human dentine sialophosphoprotein. Although there is no sequence similarity between Stm-l and Stm, Stm-l was suggested to be involved in the biomineralization of otoliths, as had been observed for Stm even before. The molecular properties and functioning of Stm-l as a putative regulatory protein in otolith formation have not been characterized yet. A comprehensive biochemical and biophysical analysis of recombinant Stm-l, along with in silico examinations, indicated that Stm-l exhibits properties of a coil-like intrinsically disordered protein. Stm-l possesses an elongated and pliable structure that is able to adopt a more ordered and rigid conformation under the influence of different factors. An in vitro assay of the biomineralization activity of Stm-l indicated that Stm-l affected the size, shape and number of calcium carbonate crystals. The functional significance of intrinsically disordered properties of Stm-l and the possible role of this protein in controlling the formation of calcium carbonate crystals is discussed. PMID:25490041

  6. Altered Placental Tryptophan Metabolism: A Crucial Molecular Pathway for the Fetal Programming of Neurodevelopmental Disorders

    DTIC Science & Technology

    2014-07-01

    Molecular Pathway for the Fetal Programming of Neurodevelopmental Disorders PRINCIPAL INVESTIGATOR: Alexandre Bonnin, PhD CONTRACTING...Fetal Programming of Neurodevelopmental Disorders 5b. GRANT NUMBER 5c. PROGRAM ELEMENT NUMBER 6. AUTHOR(S) Alexandre Bonnin, PhD; Betty...metabolism by maternal inflammation during early gestation constitutes a new molecular pathway for the fetal programming of neurodevelopmental

  7. Noninvasive metabolic profiling for painless diagnosis of human diseases and disorders

    PubMed Central

    Mal, Mainak

    2016-01-01

    Metabolic profiling provides a powerful diagnostic tool complementary to genomics and proteomics. The pain, discomfort and probable iatrogenic injury associated with invasive or minimally invasive diagnostic methods, render them unsuitable in terms of patient compliance and participation. Metabolic profiling of biomatrices like urine, breath, saliva, sweat and feces, which can be collected in a painless manner, could be used for noninvasive diagnosis. This review article covers the noninvasive metabolic profiling studies that have exhibited diagnostic potential for diseases and disorders. Their potential applications are evident in different forms of cancer, metabolic disorders, infectious diseases, neurodegenerative disorders, rheumatic diseases and pulmonary diseases. Large scale clinical validation of such diagnostic methods is necessary in future. PMID:28031956

  8. Is the Gut Microbiota a New Factor Contributing to Obesity and Its Metabolic Disorders?

    PubMed Central

    Harris, Kristina; Kassis, Amira; Major, Geneviève; Chou, Chieh J.

    2012-01-01

    The gut microbiota refers to the trillions of microorganisms residing in the intestine and is integral in multiple physiological processes of the host. Recent research has shown that gut bacteria play a role in metabolic disorders such as obesity, diabetes, and cardiovascular diseases. The mechanisms by which the gut microbiota affects metabolic diseases are by two major routes: (1) the innate immune response to the structural components of bacteria (e.g., lipopolysaccharide) resulting in inflammation and (2) bacterial metabolites of dietary compounds (e.g., SCFA from fiber), which have biological activities that regulate host functions. Gut microbiota has evolved with humans as a mutualistic partner, but dysbiosis in a form of altered gut metagenome and collected microbial activities, in combination with classic genetic and environmental factors, may promote the development of metabolic disorders. This paper reviews the available literature about the gut microbiota and aforementioned metabolic disorders and reveals the gaps in knowledge for future study. PMID:22315672

  9. [Human calcium channelopathies. Voltage-gated Ca(2+) channels in etiology, pathogenesis, and pharmacotherapy of neurologic disorders].

    PubMed

    Weiergräber, M; Hescheler, J; Schneider, T

    2008-04-01

    Voltage-gated calcium channels are key components in a variety of physiological processes. Within the last decade an increasing number of voltage-gated Ca(2+) channelopathies in both humans and animal models has been described, most of which are related to the neurologic and muscular system. In humans, mutations were found in L-type Ca(v)1.2 and Ca(v)1.4 Ca(2+) channels as well as the non-L-type Ca(v)2.1 and T-type Ca(v)3.2 channels, resulting in altered electrophysiologic properties. Based on their widespread distribution within the CNS, voltage-gated calcium channels are of particular importance in the etiology and pathogenesis of various forms of epilepsy and neuropsychiatric disorders. In this review we characterise the different human Ca(2+) channelopathies known so far, further illuminating basic pathophysiologic mechanisms and clinical aspects.

  10. Lingual dyskinesia and tics: a novel presentation of copper-metabolism disorder.

    PubMed

    Goez, Helly R; Jacob, Francois D; Yager, Jerome Y

    2011-02-01

    Copper is a trace element that is required for cellular respiration, neurotransmitter biosynthesis, pigment formation, antioxidant defense, peptide amidation, and formation of connective tissue. Abnormalities of copper metabolism have been linked with neurologic disorders that affect movement, such as Wilson disease and Menkes disease; however, the diagnosis of non-Wilson, non-Menkes-type copper-metabolism disorders has been more elusive, especially in cases with atypical characteristics. We present here the case of an adolescent with a novel presentation of copper-metabolism disorder who exhibited acute severe hemilingual dyskinesia and prominent tics, with ballismus of the upper limbs, but had normal brain and spinal MRI results and did not show any signs of dysarthria or dysphagia. His serum copper and ceruloplasmin levels were low, but his urinary copper level was elevated after penicillamine challenge. We conclude that copper-metabolism disorders should be included in the differential diagnosis for movement disorders, even in cases with highly unusual presentations, because many of them are treatable. Moreover, a connection between copper-metabolism disorders and tics is presented, to our knowledge, for the first time in humans; further investigation is needed to better establish this connection and understand its underlying pathophysiology.

  11. Magnesium deficiency and metabolic syndrome: stress and inflammation may reflect calcium activation.

    PubMed

    Rayssiguier, Yves; Libako, Patrycja; Nowacki, Wojciech; Rock, Edmond

    2010-06-01

    Magnesium (Mg) intake is inadequate in the western diet and metabolic syndrome is highly prevalent in populations around the world. Epidemiological studies suggest that high Mg intake may reduce the risk but the possibility of confounding factors exists, given the strong association between Mg and other beneficial nutriments (vegetables, fibers, cereals). The concept that metabolic syndrome is an inflammatory condition may explain the role of Mg.Mg deficiency results in a stress effect and increased susceptibility to physiological damage produced by stress. Stress activates the hypothalamic-pituitary-adrenal axis (HPA) axis and the sympathetic nervous system. The activation of the renin-angiotensin-aldosterone system is a factor in the development of insulin resistance by increasing oxidative stress. In both humans and rats, aldosteronism results in an immunostimulatory state and leads to an inflammatory phenotype. Stress response induces the release of large quantities of excitatory amino acids and activates the nuclear factor NFkappaB, promoting translation of molecules involved in cell regulation, metabolism and apoptosis. The rise in neuropeptides is also well documented. Stress-induced HPA activation has been identified to play an important role in the preferential body fat accumulation but evidence that Mg is involved in body weight regulation is lacking. One of the earliest events in the acute response to stress is endothelial dysfunction. Endothelial cells actively contribute to inflammation by elaborating cytokines, synthesizing chemical mediators and expressing adhesion molecules. Experimental Mg deficiency in rats induces a clinical inflammatory syndrome characterized by leukocyte and macrophage activation, synthesis of inflammatory cytokines and acute phase proteins, extensive production of free radicals. An increase in extracellular Mg concentration decreases inflammatory effects, while reduction in extracellular Mg results in cell activation. The

  12. Obesity, but not metabolic syndrome, negatively affects outcome in bipolar disorder.

    PubMed

    McElroy, S L; Kemp, D E; Friedman, E S; Reilly-Harrington, N A; Sylvia, L G; Calabrese, J R; Rabideau, D J; Ketter, T A; Thase, M E; Singh, V; Tohen, M; Bowden, C L; Bernstein, E E; Brody, B D; Deckersbach, T; Kocsis, J H; Kinrys, G; Bobo, W V; Kamali, M; McInnis, M G; Leon, A C; Faraone, S; Nierenberg, A A; Shelton, R C

    2015-06-26

    Examine the effects of obesity and metabolic syndrome on outcome in bipolar disorder. The Comparative Effectiveness of a Second Generation Antipsychotic Mood Stabilizer and a Classic Mood Stabilizer for Bipolar Disorder (Bipolar CHOICE) study randomized 482 participants with bipolar disorder in a 6-month trial comparing lithium- and quetiapine-based treatment. Baseline variables were compared between groups with and without obesity, with and without abdominal obesity, and with and without metabolic syndrome respectively. The effects of baseline obesity, abdominal obesity, and metabolic syndrome on outcomes were examined using mixed effects linear regression models. At baseline, 44.4% of participants had obesity, 48.0% had abdominal obesity, and 27.3% had metabolic syndrome; neither obesity, nor abdominal obesity, nor metabolic syndrome were associated with increased global severity, mood symptoms, or suicidality, or with poorer functioning or life satisfaction. Treatment groups did not differ on prevalence of obesity, abdominal obesity, or metabolic syndrome. By contrast, among the entire cohort, obesity was associated with less global improvement and less improvement in total mood and depressive symptoms, suicidality, functioning, and life satisfaction after 6 months of treatment. Abdominal obesity was associated with similar findings. Metabolic syndrome had no effect on outcome. Obesity and abdominal obesity, but not metabolic syndrome, were associated with less improvement after 6 months of lithium- or quetiapine-based treatment. © 2015 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

  13. Strategies for Reversing the Effects of Metabolic Disorders Induced as a Consequence of Developmental Programming

    PubMed Central

    Vickers, M. H.; Sloboda, D. M.

    2012-01-01

    Obesity and the metabolic syndrome have reached epidemic proportions worldwide with far-reaching health care and economic implications. The rapid increase in the prevalence of these disorders suggests that environmental and behavioral influences, rather than genetic causes, are fueling the epidemic. The developmental origins of health and disease hypothesis has highlighted the link between the periconceptual, fetal, and early infant phases of life and the subsequent development of metabolic disorders in later life. In particular, the impact of poor maternal nutrition on susceptibility to later life metabolic disease in offspring is now well documented. Several studies have now shown, at least in experimental animal models, that some components of the metabolic syndrome, induced as a consequence of developmental programming, are potentially reversible by nutritional or targeted therapeutic interventions during windows of developmental plasticity. This review will focus on critical windows of development and possible therapeutic avenues that may reduce metabolic and obesogenic risk following an adverse early life environment. PMID:22783205

  14. The role of metabolic disorders in Alzheimer disease and vascular dementia: two roads converged.

    PubMed

    Craft, Suzanne

    2009-03-01

    In recent years a rapidly increasing number of studies has focused on the relationship between dementia and metabolic disorders such as diabetes, obesity, hypertension, and dyslipidemia. Etiological heterogeneity and comorbidity pose challenges for determining relationships among metabolic disorders. The independent and interactive effects of brain vascular injury and classic pathological agents such as beta-amyloid have also proved difficult to distinguish in human patients, blurring the lines between Alzheimer disease and vascular dementia. This review highlights recent work aimed at identifying convergent mechanisms such as insulin resistance that may underlie comorbid metabolic disorders and thereby increase dementia risk. Identification of such convergent factors will not only provide important insight into the causes and interdependencies of late-life dementias but will also inspire novel strategies for treating and preventing these disorders.

  15. The Role of Metabolic Disorders in Alzheimer's Disease and Vascular Dementia: Two Roads Converged?

    PubMed Central

    Craft, Suzanne

    2009-01-01

    In recent years, there has been a rapidly increasing number of studies focused on the relationship between dementia and metabolic disorders such as diabetes, obesity, hypertension and dyslipidemia. Etiological heterogeneity and co-morbidity pose challenges for determining relationships among metabolic disorders. The independent and interactive effects of brain vascular injury and classic pathological agents such as Aβ have also proved difficult to untangle in human patients, blurring the lines between Alzheimer's disease and vascular dementia. This review highlights recent work aimed at identifying convergent mechanisms such as insulin resistance that may underlie co-morbid metabolic disorders and thereby increase dementia risk. Identification of such convergent factors will not only provide important insights into the causes and interdependencies of late-life dementias, but will also inspire novel strategies for treating and preventing these disorders. PMID:19273747

  16. Allogeneic Bone Marrow Transplant for Inherited Metabolic Disorders

    ClinicalTrials.gov

    2018-01-09

    Mucopolysaccharidosis; Hurler Syndrome; Hunter Syndrome; Maroteaux-Lamy Syndrome; Sly Syndrome; Alpha Mannosidosis; Fucosidosis; Aspartylglucosaminuria; Adrenoleukodystrophy (ALD); Krabbe Disease; Metachromatic Leukodystrophy (MLD); Sphingolipidoses; Peroxisomal Disorders

  17. Biochemical effects of lead exposure on battery manufacture workers with reference to blood pressure, calcium metabolism and bone mineral density.

    PubMed

    Dongre, Nilima N; Suryakar, Adinath N; Patil, Arun J; Hundekari, Indira A; Devarnavadagi, Basavaraj B

    2013-01-01

    Calcium, Ionized calcium, phosphorus were significantly decreased (P < 0.001) in all the three study groups. Serum vitamin D levels were lowered (P < 0.01) and serum PTH was increased (P < 0.01) in workers as compared to controls. The results of this study clearly indicate that the absorption of lead is more in these workers which adversely affects blood pressure, disturbs calcium and phosphorus metabolism which further impairs mineralization of bone resulting in decreased bone mineral density observed in these workers. Lead toxicity is still persistent in battery manufacture workers though they are using sophisticated techniques in these industries. There is a need to protect the workers from the health hazards of occupational lead exposure.

  18. Substrate specific effects of calcium on metabolism of rat heart mitochondria.

    PubMed

    Panov, A V; Scaduto, R C

    1996-04-01

    Oxidative metabolism in the heart is tightly coupled to mechanical work. Because this coupling process is believed to involve Ca2+, the roles of mitochondrial Ca2+ in the regulation of oxidative phosphorylation was studied in isolated rat heart mitochondria. The electrical component of the mitochondrial membrane potential (delta psi) and the redox state of the pyridine nucleotides were determined during the oxidation of various substrates under different metabolic states. In the absence of added adenine nucleotides, the NADP+ redox couple was almost completely reduced, regardless of the specific substrate and the presence of Ca2+, whereas NAD+ couple redox state was highly dependent on the substrate type and the presence of Ca2+. Titration of respiration with ADP, in the presence of excess hexokinase and glucose, showed that both respiration and NAD(P)+ reduction were very sensitive to ADP. The maximal enzyme reaction rate of ADP-stimulated respiration Michaelis constants (Km) for ADP were dependent on the particular substrate employed. delta psi was much less sensitive to ADP. With either alpha-ketoglutarate or glutamate as substrate, Ca2+ significantly increased reduction of NAD(P)+.Ca2+ did not influence NAD(P)+ reduction with either acetylcarnitine or pyruvate as substrate. In the presence of ADP, delta psi was increased by Ca2+ at all metabolic states with glutamate plus malate, 0.5 mM alpha-ketoglutarate plus malate, or pyruvate plus malate as substrates. The data presented support the hypothesis that cardiac respiration is controlled by the availability of both Ca2+ and ADP to mitochondria. The data indicate that an increase in substrate supply to mitochondria can increase mitochondrial respiration at given level of ADP. This effect can be produced by Ca2+ with substrates such as glutamate, which utilize alpha-ketoglutarate dehydrogenase activity for oxidation. Increases in respiration by Ca2+ may mitigate an increase in ADP during periods of increased

  19. Interactions of Mitochondria/Metabolism and Calcium Regulation in Alzheimer’s Disease - A Calcinist Point of View

    PubMed Central

    Gibson, Gary E.; Thakkar, Ankita

    2017-01-01

    Decades of research suggest that alterations in calcium are central to the pathophysiology of Alzheimer’s Disease (AD). Highly reproducible changes in calcium dynamics occur in cells from patients with both genetic and non-genetic forms of AD relative to controls. The most robust change is an exaggerated release of calcium from internal stores. Detailed analysis of these changes in animal and cell models of the AD-causing presenilin mutations reveal robust changes in ryanodine receptors, inositol tris-phosphate receptors, calcium leak channels and store activated calcium entry. Similar anomalies in calcium result when AD-like changes in mitochondrial enzymes or oxidative stress are induced experimentally. The calcium abnormalities can be directly linked to the altered tau phosphorylation, amyloid precursor protein processing and synaptic dysfunction that are defining features of AD. A better understanding of these changes is required before using calcium abnormalities as therapeutic targets. PMID:28181072

  20. Psychosocial and metabolic function by smoking status in individuals with binge eating disorder and obesity.

    PubMed

    Udo, Tomoko; White, Marney A; Barnes, Rachel D; Ivezaj, Valentina; Morgan, Peter; Masheb, Robin M; Grilo, Carlos M

    2016-02-01

    Individuals with binge eating disorder (BED) report smoking to control appetite and weight. Smoking in BED is associated with increased risk for comorbid psychiatric disorders, but its impact on psychosocial functioning and metabolic function has not been evaluated. Participants were 429 treatment-seeking adults (72.4% women; mean age 46.2±11.0years old) with BED comorbid with obesity. Participants were categorized into current smokers (n=66), former smokers (n=145), and never smokers (n=218). Smoking status was unrelated to most historical eating/weight variables and to current eating disorder psychopathology. Smoking status was associated with psychiatric, psychosocial, and metabolic functioning. Compared with never smokers, current smokers were more likely to meet lifetime diagnostic criteria for alcohol (OR=5.51 [95% CI=2.46-12.33]) and substance use disorders (OR=7.05 [95% CI=3.37-14.72]), poorer current physical quality of life, and increased risk for metabolic syndrome (OR=1.80 [95% CI=0.97-3.35]) and related metabolic risks (reduced HDL, elevated total cholesterol). On the other hand, the odds of meeting criteria for lifetime psychiatric comorbidity or metabolic abnormalities were not significantly greater in former smokers, relative to never smokers. Our findings suggest the importance of promoting smoking cessation in treatment-seeking patients with BED and obesity for its potential long-term implications for psychiatric and metabolic functioning. Copyright © 2015 Elsevier Ltd. All rights reserved.

  1. Endocrine and metabolic disorders associated with human immune deficiency virus infection.

    PubMed

    Unachukwu, C N; Uchenna, D I; Young, E E

    2009-01-01

    Many reports have described endocrine and metabolic disorders in the human immunodeficiency virus (HIV) infection. This article reviewed various reports in the literature in order to increase the awareness and thus the need for early intervention when necessary. Data were obtained from MEDLINE, Google search and otherjournals on 'HIV, Endocrinopathies/Metabolic Disorders' from 1985 till 2007. Studies related to HIV associated endocrinopathies and metabolic disorders in the last two decades were reviewed. Information on epidemiology, pathogenesis, diagnosis and treatment of the target organ endocrinopathies and metabolic disorders in HIV/AIDS were extracted from relevant literature. Endocrine and metabolic disturbances occur in the course of HIV infection. Pathogenesis includes direct infection of endocrine glands by HIV or opportunistic organisms, infiltration by neoplasms and side effects of drugs. Adrenal insufficiency is the commonest HIV endocrinopathy with cytomegalovirus adrenalitis occurring in 40-88% of cases. Thyroid dysfunction may occur as euthyroid sick syndrome or sub-clinical hypothyroidism. Hypogonadotrophic dysfunction accounts for 75% of HIV-associated hypogonadism, with prolonged amenorrhoea being three times more likely in the women. Pancreatic dysfunction may result in hypoglycaemia or diabetes mellitus (DM). Highly active antiretroviral therapy (HAART) especially protease inhibitors has been noted to result in insulin resistance and lipodystrophy. Virtually every endocrine organ is involved in the course of HIV infection. Detailed endocrinological and metabolic evaluation and appropriate treatment is necessary in the optimal management of patients with HIV infection in our environment.

  2. Emerging Potential of Natural Products as an Alternative Strategy to Pharmacological Agents Used Against Metabolic Disorders.

    PubMed

    Dias, Tânia R; Bernardino, Raquel L; Meneses, Maria J; Sousa, Mário; Sá, Rosália; Alves, Marco G; Silva, Branca M; Oliveira, Pedro F

    2016-01-01

    Human metabolism is an essential biological process that involves the consumption of different substrates to ensure the nutritional and energetic needs of cells. The disruption of this highly regulated system constitutes the onset of several disorders/dysfunctions such as diabetes mellitus, cardiovascular diseases and hypertension. In this review, we propose to discuss promising natural products that can act as modulators of cell metabolism and point towards possible targets to take into account in the development of new therapies against metabolic diseases. After having defined our main focus, we undertook an intensive search of bibliographic databases to select the peer-reviewed papers that fits within the review thematic. The information of the screened papers was described in an organized manner through the review and different types of studies were included. Two hundred and seventy papers were included in the review, as well as one reliable website from the World Health Organization. Several articles described that pharmacological agents are commonly used to counteract metabolic disorders. However, in many cases these products are insufficient, represent high costs to health care systems and are associated with several undesirable effects, highlighting the need to search for new therapies. Notably, many papers reported the promising results of natural products in the treatment of several metabolic disorders, constituting a possible alternative or complementary strategy to pharmacological agents. The findings of this review confirm that the currently available treatments for metabolic disorders and its associated complications remain far below the expected results.

  3. Autonomic nervous system and lipid metabolism: findings in anxious-depressive spectrum and eating disorders.

    PubMed

    Pistorio, Elisabetta; Luca, Maria; Luca, Antonina; Messina, Vincenzo; Calandra, Carmela

    2011-10-28

    To correlate lipid metabolism and autonomic dysfunction with anxious-depressive spectrum and eating disorders. To propose the lipid index (LI) as a new possible biomarker. 95 patients and 60 controls were enrolled from the University Psychiatry Unit of Catania and from general practitioners (GPs). The patients were divided into four pathological groups: Anxiety, Depression, Anxious-Depressive Disorder and Eating Disorders [Diagnostic and Statistical Manual of Mental Disorders Fourth Edition Text Revision (DSM-IV-TR) official/appendix criteria]. The levels of the cholesterol, triglycerides and apolipoproteins A and B were determined. The LI, for each subject, was obtained through a mathematical operation on the values of the cholesterol and triglycerides levels compared with the maximum cut-off of the general population. The autonomic functioning was tested with Ewing battery tests. Particularly, the correlation between heart rate variability (HRV) and lipid metabolism has been investigated. Pathological and control groups, compared among each other, presented some peculiarities in the lipid metabolism and the autonomic dysfunction scores. In addition, a statistically significant correlation has been found between HRV and lipid metabolism. Lipid metabolism and autonomic functioning seem to be related to the discussed psychiatric disorders. LI, in addition, could represent a new possible biomarker to be considered.

  4. Impact of antiretroviral therapy on selected metabolic disorders - pilot study.

    PubMed

    Bociąga-Jasik, Monika; Polus, Anna; Góralska, Joanna; Raźny, Urszula; Siedlecka, Dominika; Zapała, Barbara; Chrzan, Robert; Garlicki, Aleksander; Mach, Tomasz; Dembińska-Kieć, Aldona

    2014-01-01

    Taking into consideration the aging of HIV infected individuals, changes in the metabolism aggravated by the antiretroviral therapy significantly impact their health. Mechanisms responsible for lipodystrophy, dyslipidemia and insulin resistance (IR) occurrence have not been completely understood. Only recently, the free fatty acids (FFAs) metabolic turnover has become considered to be the independent risk factor for cardiovascular complications. We designed the follow-up study in which patients were recruited before the introduction of ARV therapy and then observed up to 1 year. The impact of ARV therapy on the development of metabolic complications, inflammation markers and changes in adipokines secretion was investigated. The fasting and postprandial responses of FFAs, triglycerides (TG), glucose, insulin and glucose-dependent insulinotropic peptide (GIP) were measured. Changes in body composition were followed by impedance and a CT scan of adipose tissue volume of the abdomen and thighs. Significant impact of ARV therapy on metabolic disturbances was reported. Not only fasting, but also postprandial levels of FFAs and TG were found to increase during the follow up. The increased concentration of FFAs is suggested to be the triggering event in the development of hypertriglyceridemia and insulin resistance during ARV therapy. Changes in postprandial FFAs and TG during the follow up indicate the increasing risk of cardiovascular diseases. We conclude that modern ARV therapy during the period of 12 months does not induce changes in the fat distribution, although increased limb fat correlated with higher plasma leptin level, which may be the marker of increased risk of metabolic driven cardiovascular complications.

  5. Sleep, sleep-disordered breathing and metabolic consequences.

    PubMed

    Lévy, P; Bonsignore, M R; Eckel, J

    2009-07-01

    Sleep profoundly affects metabolic pathways. In healthy subjects, experimental sleep restriction caused insulin resistance (IR) and increased evening cortisol and sympathetic activation. Increased obesity in subjects reporting short sleep duration leads to speculation that, during recent decades, decreased sleeping time in the general population may have contributed to the increasing prevalence of obesity. Causal inference is difficult due to lack of control for confounders and inconsistent evidence of temporal sequence. In the general population, obstructive sleep apnoea (OSA) is associated with glucose intolerance. OSA severity is also associated with the degree of IR. However, OSA at baseline does not seem to significantly predict the development of diabetes. Prevalence of the metabolic syndrome is higher in patients with OSA than in obese subjects without OSA. Treatment with continuous positive airway pressure seems to improve glucose metabolism both in diabetic and nondiabetic OSA but mainly in nonobese subjects. The relative role of obesity and OSA in the pathogenesis of metabolic alterations is still unclear and is intensively studied in clinical and experimental models. In the intermittent hypoxia model in rodents, strong interactions are likely to occur between haemodynamic alterations, systemic inflammation and metabolic changes, modulated by genetic background. Molecular and cellular mechanisms are currently being investigated.

  6. Disorder of endoplasmic reticulum calcium channel components is associated with the increased apoptotic potential in pale, soft, exudative pork.

    PubMed

    Guo, Bing; Zhang, Wangang; Tume, Ron K; Hudson, Nicholas J; Huang, Feng; Yin, Yan; Zhou, Guanghong

    2016-05-01

    Eight pale, soft and exudative (PSE) and eight reddish-pink, firm and non-exudative (RFN) porcine longissimus muscle samples were selected based on pH and L* at 1h postmortem (PM), and drip loss at 24h PM, and used to evaluate the cellular calcium and apoptosis status. We found that SERCA1 was decreased, while IP3R was decreased in PSE meat (P<0.05), indicative of the overloaded sarcoplasmic calcium status. In PSE meat, the pro-apoptotic factor BAX was increased while the anti-apoptotic factor Bcl-2 was decreased (P<0.05). The significantly increased activity of caspase 3 and the expression of its cleavage fragment suggested higher apoptotic potential in PSE meat compared with RFN meat (P<0.05). Moreover, the significantly higher expression level of cytochrome C (P<0.05) suggests the important role of mitochondria during apoptosis appearance in PSE meat. Taken together, our data inferred that the calcium channel disorder present in PSE meat was associated with the increased apoptotic potential. Copyright © 2016 Elsevier Ltd. All rights reserved.

  7. Effects of calcium-vitamin D co-supplementation on metabolic profiles in vitamin D insufficient people with type 2 diabetes: a randomised controlled clinical trial.

    PubMed

    Tabesh, Marjan; Azadbakht, Leila; Faghihimani, Elham; Tabesh, Maryam; Esmaillzadeh, Ahmad

    2014-10-01

    This study was performed to assess the effects of vitamin D and calcium supplementation on the metabolic profiles of vitamin D insufficient persons with type 2 diabetes. In a parallel designed randomised placebo-controlled clinical trial, a total of 118 non-smoker individuals with type 2 diabetes and insufficient 25-hydroxyvitamin D, aged >30 years, were recruited from the Isfahan Endocrine and Metabolism Research Centre. Participants were randomly assigned to four groups receiving: (1) 50,000 U/week vitamin D + calcium placebo; (2) 1,000 mg/day calcium + vitamin D placebo; (3) 50,000 U/week vitamin D + 1,000 mg/day calcium; or (4) vitamin D placebo + calcium placebo for 8 weeks. A study technician carried out the random allocations using a random numbers table. All investigators, participants and laboratory technicians were blinded to the random assignments. All participants provided 3 days of dietary records and 3 days of physical activity records throughout the intervention. Blood samples were taken to quantify glycaemic and lipid profiles at study baseline and after 8 weeks of intervention. 30 participants were randomised in each group. During the intervention, one participant from the calcium group and one from the vitamin D group were excluded because of personal problems. Calcium-vitamin D co-supplementation resulted in reduced serum insulin (changes from baseline: -14.8 ± 3.9 pmol/l, p = 0.01), HbA1c [-0.70 ± 0.19% (-8.0 ± 0.4 mmol/mol), p = 0.02], HOMA-IR (-0.46 ± 0.20, p = 0.001), LDL-cholesterol (-10.36 ± 0.10 mmol/l, p = 0.04) and total/HDL-cholesterol levels (-0.91 ± 0.16, p = 0.03) compared with other groups. We found a significant increase in QUICKI (0.025 ± 0.01, p = 0.004), HOMA of beta cell function (HOMA-B; 11.8 ± 12.17, p = 0.001) and HDL-cholesterol (0.46 ± 0.05 mmol/l, p = 0.03) in the calcium-vitamin D group compared with others. Joint calcium and vitamin D supplementation might improve the glycaemic status and lipid profiles of

  8. DISTURBANCES IN CALCIUM METABOLISM AND CARDIOMYOCYTE NECROSIS: THE ROLE OF CALCITROPIC HORMONES

    PubMed Central

    Yusuf, Jawwad; Khan, M. Usman; Cheema, Yaser; Bhattacharya, Syamal K.; Weber, Karl T.

    2012-01-01

    Summary A synchronized dyshomeostasis of extra- and intracellular Ca2+, expressed as plasma ionized hypocalcemia and excessive intracellular Ca2+ accumulation, respectively, represents a common pathophysiologic scenario that accompanies a number of diverse disorders. These include low-renin and salt-sensitive hypertension, primary aldosteronism and hyperparathyroidism, congestive heart failure, acute and chronic hyperadrenergic stressor states, high dietary Na+, and low dietary Ca2+ with hypovitaminosis D. Homeostatic responses are invoked to restore normal extracellular [Ca2+]o, including increased plasma levels of parathyroid hormone and 1,25(OH)2D3. However, in cardiomyocytes, these calcitropic hormones concurrently promote cytosolic free [Ca2+]i and mitochondrial [Ca2+]m overloading. The latter sets into motion organellar-based oxidative stress, in which the rate of reactive oxygen species generation overwhelms their detoxification by endogenous antioxidant defenses, including those related to intrinsically coupled increments in intracellular Zn2+. In turn, the opening potential of the mitochondrial permeability transition pore increases allowing for osmotic swelling and ensuing organellar degeneration. Collectively, these pathophysiologic events represent the major components to a mitochondriocentric signal-transducer-effector pathway to cardiomyocyte necrosis. From necrotic cells there follows a spillage of intracellular contents, including troponins, and a subsequent wound healing response with reparative fibrosis, or scarring. Taken together the loss of terminally differentiated cardiomyocytes from this postmitotic organ and the ensuing replacement fibrosis each contribute to the adverse structural remodeling of myocardium and progressive nature of heart failure. In conclusion, hormone-induced ionized hypocalcemia and intracellular Ca2+ overloading comprise a pathophysiologic cascade common to diverse disorders and which initiates a mitochondriocentric

  9. Deconstructing Black Swans: An Introductory Approach to Inherited Metabolic Disorders in the Neonate.

    PubMed

    Mew, Nicholas Ah; Viall, Sarah; Kirmse, Brian; Chapman, Kimberly A

    2015-08-01

    Inherited metabolic disorders (IMDs) are individually rare but collectively common disorders that frequently require rapid or urgent therapy. This article provides a generalized approach to IMDs, as well as some investigations and safe therapies that may be initiated pending the metabolic consult. An overview of the research supporting management strategies is provided. In addition, the newborn metabolic screen is reviewed. Caring for infants with IMDs can seem difficult because each of the types is rarely seen; however, collectively the management can be seen as similar. When an IMD is suspected, a metabolic specialist should be consulted for expert advice regarding appropriate laboratory investigations and management. Because rapid intervention of IMDs before the onset of symptoms may prevent future irreversible sequelae, each abnormal newborn screen must be addressed promptly. Management can be difficult. Research in this area is limited and can be difficult without multisite coordination since sample sizes of any significance are difficult to achieve.

  10. Mutation/SNP analysis in EF-hand calcium binding domain of mitochondrial Ca[Formula: see text] uptake 1 gene in bipolar disorder patients.

    PubMed

    Safari, Roghaiyeh; Salimi, Reza; Tunca, Zeliha; Ozerdem, Aysegul; Ceylan, Deniz; Sakizli, Meral

    2016-06-01

    Calcium signaling is important for synaptic plasticity, generation of brain rhythms, regulating neuronal excitability, data processing and cognition. Impairment in calcium homeostasis contributed to the development of psychiatric disorders such as bipolar disorder (BP). MCU is the most important calcium transporter in mitochondria inner membrane responsible for influx of Ca[Formula: see text]. MICU1 is linked with MCU and has two canonical EF hands that are vital for its activity and regulates MCU-mediated Ca[Formula: see text] influx. In the current study, we aimed to investigate the role of genetic alteration of EF hand calcium binding motifs of MICU1 on the development of BP. We examined patients with BP, first degree relatives of these patients and healthy volunteers for mutations and polymorphisms in EF hand calcium binding motifs of MICU1. The result showed no SNP/mutation in BP patients, in healthy subjects and in first degree relatives. Additionally, alignment of the EF hand calcium binding regions among species (Gallus-gallus, Canis-lupus-familiaris, Bos-taurus, Mus-musculus, Rattus-norvegicus, Pan-troglodytes, Homosapiens and Danio-rerio) showed exactly the same amino acids (DLNGDGEVDMEE and DCDGNGELSNKE) except in one of the calcium binding domain of Danio-rerio that there was only one difference; leucine instead of Methionine. Our results showed that the SNP on EF-hand Ca[Formula: see text] binding domains of MICU1 gene had no effect in phenotypic characters of BP patients.

  11. Inflammatory and Metabolic Dysregulation and the 2-Year Course of Depressive Disorders in Antidepressant Users

    PubMed Central

    Vogelzangs, Nicole; Beekman, Aartjan TF; van Reedt Dortland, Arianne KB; Schoevers, Robert A; Giltay, Erik J; de Jonge, Peter; Penninx, Brenda WJH

    2014-01-01

    Scarce evidence suggests that inflammatory and metabolic dysregulation predicts poor response to antidepressants, which could result in worse depression outcome. This study prospectively examined whether inflammatory and metabolic dysregulation predicted the 2-year course of depressive disorders among antidepressant users. Data were from the Netherlands Study of Depression and Anxiety, including 315 persons (18–65 years) with a current depressive disorder (major depressive disorder, dysthymia) at baseline according to the DSM-IV criteria and using antidepressants. Inflammatory (C-reactive protein, interleukin-6 (IL-6), tumor-necrosis factor-α) and metabolic (waist circumference, triglycerides, high-density lipoprotein (HDL) cholesterol, blood pressure, fasting glucose) factors were measured at baseline. Primary outcome for course of depression was indicated by whether or not a DSM-IV depressive disorder diagnosis was still/again present at 2-year follow-up, indicating chronicity of depression. Elevated IL-6, low HDL cholesterol, hypertriglyceridemia, and hyperglycemia were associated with chronicity of depression in antidepressant users. Persons showing ⩾4 inflammatory or metabolic dysregulations had a 1.90 increased odds of depression chronicity (95% CI=1.12–3.23). Among persons who recently (ie, at most 3 months) started antidepressant medication (N=103), having ⩾4 dysregulations was associated with a 6.85 increased odds of depression chronicity (95% CI=1.95–24.06). In conclusion, inflammatory and metabolic dysregulations were found to predict a more chronic course of depressive disorders among patients using antidepressants. This could suggest that inflammatory and metabolic dysregulation worsens depression course owing to reduced antidepressant treatment response and that alternative intervention treatments may be needed for depressed persons with inflammatory and metabolic dysregulation. PMID:24442097

  12. Metabolic Acidosis Increases Intracellular Calcium in Bone Cells Through Activation of the Proton Receptor OGR1

    PubMed Central

    Frick, Kevin K; Krieger, Nancy S; Nehrke, Keith; Bushinsky, David A

    2009-01-01

    Metabolic acidosis increases urine Ca without increasing intestinal absorption, leading to bone Ca loss. It is unclear how bone cells detect the increase in proton concentration. To determine which G protein-coupled proton sensing receptors are expressed in bone, PCR was performed, and products were detected for OGR1, TDAG8, G2A, and GPR4. We tested the hypothesis that the G protein-coupled proton sensor, OGR1, is an H+-sensing receptor in bone. To determine whether acid-induced bone resorption involves OGR1, we incubated mouse calvariae in neutral pH (NTL) or acidic (MET) medium ± the OGR1 inhibitor CuCl2. CuCl2 decreased MET-induced Ca efflux. We used fluorescent imaging of perfused bone cells to determine whether MET increases Cai. Perfusion with MET induced a rapid, flow-independent, increase in Cai in individual bone cells. To determine whether transfection of OGR1 into a heterologous cell type would increase Cai in response to H+, we perfused Chinese hamster ovary (CHO) cells transfected with mouse OGR1 cDNA. Perfusion with MET induced a rapid increase in Cai in OGR1-transfected CHO cells. These data indicate that OGR1 induces an increase in Cai in response to MET and is a prime candidate for an osteoblast proton sensor. PMID:18847331

  13. Metabolic acidosis increases intracellular calcium in bone cells through activation of the proton receptor OGR1.

    PubMed

    Frick, Kevin K; Krieger, Nancy S; Nehrke, Keith; Bushinsky, David A

    2009-02-01

    Metabolic acidosis increases urine Ca without increasing intestinal absorption, leading to bone Ca loss. It is unclear how bone cells detect the increase in proton concentration. To determine which G protein-coupled proton sensing receptors are expressed in bone, PCR was performed, and products were detected for OGR1, TDAG8, G2A, and GPR4. We tested the hypothesis that the G protein-coupled proton sensor, OGR1, is an H(+)-sensing receptor in bone. To determine whether acid-induced bone resorption involves OGR1, we incubated mouse calvariae in neutral pH (NTL) or acidic (MET) medium +/- the OGR1 inhibitor CuCl(2). CuCl(2) decreased MET-induced Ca efflux. We used fluorescent imaging of perfused bone cells to determine whether MET increases Ca(i). Perfusion with MET induced a rapid, flow-independent, increase in Ca(i) in individual bone cells. To determine whether transfection of OGR1 into a heterologous cell type would increase Ca(i) in response to H(+), we perfused Chinese hamster ovary (CHO) cells transfected with mouse OGR1 cDNA. Perfusion with MET induced a rapid increase in Ca(i) in OGR1-transfected CHO cells. These data indicate that OGR1 induces an increase in Ca(i) in response to MET and is a prime candidate for an osteoblast proton sensor.

  14. Effects of dietary carbohydrates on metabolism of calcium and other minerals in normal subjects and patients with noninsulin-dependent diabetes mellitus.

    PubMed

    Garg, A; Bonanome, A; Grundy, S M; Unger, R H; Breslau, N A; Pak, C Y

    1990-04-01

    Transient hypercalciuria has been noted after high carbohydrate meals which is independent of dietary calcium and is probably due to impaired renal calcium reabsorption mediated by an increase in plasma insulin levels. Based on these observations, some investigators believe that long term intake of high carbohydrate diets may increase the risk of nephrolithiasis and possibly osteoporosis. Using a randomized cross-over design, we compared high carbohydrate diets (60% carbohydrate and 25% fat) with high fat diets (50% fat and 35% carbohydrate) for effects on metabolism of calcium and other minerals in eight normal subjects and eight euglycemic patients with noninsulin-dependent diabetes mellitus. All other dietary constituents, such as protein, fiber, fluid, minerals (including Ca, Mg, Na, K, and P), and caffeine intake, were kept constant. Despite higher daylong levels of plasma insulin on the high carbohydrate diets compared to the high fat diet in both normal and noninsulin-dependent diabetic subjects, no changes in daily urinary excretion of calcium or other constituents, associated with renal stone risk, were observed. Furthermore, there was no change in fractional intestinal 47Ca absorption. Although hypercalciuria may ensue transiently after high carbohydrate meals, we conclude that substitution of simple or complex carbohydrates for fats in an isocaloric manner for a longer duration does not result in significant urinary calcium loss, and therefore, high intakes of digestible carbohydrates may not increase the risk of nephrolithiasis or osteoporosis via this mechanism.

  15. The effect of supplementation of calcium, vitamin D, boron, and increased fluoride intake on bone mechanical properties and metabolic hormones in rat.

    PubMed

    Ghanizadeh, G; Babaei, M; Naghii, Mohammad Reza; Mofid, M; Torkaman, G; Hedayati, M

    2014-04-01

    Evidence indicates that optimal nutrition plays a role in bone formation and maintenance. Besides major components of mineralization such as calcium, phosphorus, and vitamin D, other nutrients like boron and fluoride have beneficial role, too. In this study, 34 male Wistar rats were divided into five groups: control diet, fluoride, fluoride + boron, fluoride + calcium + vitamin D, and fluoride + boron + calcium + vitamin D. Boron equal to 1.23 mg, calcium and vitamin D equal to 210 mg + 55 IU and fluoride equal to 0.7 mg/rat/day was added to their drinking water for 8 weeks. Plasma blood samples and bones were collected. Findings are evidence that fluoride + boron intake revealed significant positive effects on bone mechanical properties and bone metabolic hormones. These findings suggest that combined intake of these two elements has beneficial effects on bone stiffness and breaking strength comparing to even calcium + vitamin D supplementation. This evidence dealing with health problems related to bone and skeletal system in humans should justify further investigation of the role of boron and fluoride with other elements in relation to bone.

  16. Probiotics and Prebiotics: Present Status and Future Perspectives on Metabolic Disorders.

    PubMed

    Yoo, Ji Youn; Kim, Sung Soo

    2016-03-18

    Metabolic disorders, including type 2 diabetes (T2DM) and cardiovascular disease (CVD), present an increasing public health concern and can significantly undermine an individual's quality of life. The relative risk of CVD, the primary cause of death in T2DM patients, is two to four times higher in people with T2DM compared with those who are non-diabetic. The prevalence of metabolic disorders has been associated with dynamic changes in dietary macronutrient intake and lifestyle changes over recent decades. Recently, the scientific community has considered alteration in gut microbiota composition to constitute one of the most probable factors in the development of metabolic disorders. The altered gut microbiota composition is strongly conducive to increased adiposity, β-cell dysfunction, metabolic endotoxemia, systemic inflammation, and oxidative stress. Probiotics and prebiotics can ameliorate T2DM and CVD through improvement of gut microbiota, which in turn leads to insulin-signaling stimulation and cholesterol-lowering effects. We analyze the currently available data to ascertain further potential benefits and limitations of probiotics and prebiotics in the treatment of metabolic disorders, including T2DM, CVD, and other disease (obesity). The current paper explores the relevant contemporary scientific literature to assist in the derivation of a general perspective of this broad area.

  17. Probiotics and Prebiotics: Present Status and Future Perspectives on Metabolic Disorders

    PubMed Central

    Yoo, Ji Youn; Kim, Sung Soo

    2016-01-01

    Metabolic disorders, including type 2 diabetes (T2DM) and cardiovascular disease (CVD), present an increasing public health concern and can significantly undermine an individual’s quality of life. The relative risk of CVD, the primary cause of death in T2DM patients, is two to four times higher in people with T2DM compared with those who are non-diabetic. The prevalence of metabolic disorders has been associated with dynamic changes in dietary macronutrient intake and lifestyle changes over recent decades. Recently, the scientific community has considered alteration in gut microbiota composition to constitute one of the most probable factors in the development of metabolic disorders. The altered gut microbiota composition is strongly conducive to increased adiposity, β-cell dysfunction, metabolic endotoxemia, systemic inflammation, and oxidative stress. Probiotics and prebiotics can ameliorate T2DM and CVD through improvement of gut microbiota, which in turn leads to insulin-signaling stimulation and cholesterol-lowering effects. We analyze the currently available data to ascertain further potential benefits and limitations of probiotics and prebiotics in the treatment of metabolic disorders, including T2DM, CVD, and other disease (obesity). The current paper explores the relevant contemporary scientific literature to assist in the derivation of a general perspective of this broad area. PMID:26999199

  18. Branched-chain amino acid metabolism: from rare Mendelian diseases to more common disorders

    PubMed Central

    Burrage, Lindsay C.; Nagamani, Sandesh C.S.; Campeau, Philippe M.; Lee, Brendan H.

    2014-01-01

    Branched-chain amino acid (BCAA) metabolism plays a central role in the pathophysiology of both rare inborn errors of metabolism and the more common multifactorial diseases. Although deficiency of the branched-chain ketoacid dehydrogenase (BCKDC) and associated elevations in the BCAAs and their ketoacids have been recognized as the cause of maple syrup urine disease (MSUD) for decades, treatment options for this disorder have been limited to dietary interventions. In recent years, the discovery of improved leucine tolerance after liver transplantation has resulted in a new therapeutic strategy for this disorder. Likewise, targeting the regulation of the BCKDC activity may be an alternative potential treatment strategy for MSUD. The regulation of the BCKDC by the branched-chain ketoacid dehydrogenase kinase has also been implicated in a new inborn error of metabolism characterized by autism, intellectual disability and seizures. Finally, there is a growing body of literature implicating BCAA metabolism in more common disorders such as the metabolic syndrome, cancer and hepatic disease. This review surveys the knowledge acquired on the topic over the past 50 years and focuses on recent developments in the field of BCAA metabolism. PMID:24651065

  19. Fatty Acids Consumption: The Role Metabolic Aspects Involved in Obesity and Its Associated Disorders

    PubMed Central

    Carla Inada, Aline; Marcelino, Gabriela; Maiara Lopes Cardozo, Carla; de Cássia Freitas, Karine; de Cássia Avellaneda Guimarães, Rita; Pereira de Castro, Alinne; Aragão do Nascimento, Valter; Aiko Hiane, Priscila

    2017-01-01

    Obesity and its associated disorders, such as insulin resistance, dyslipidemia, metabolic inflammation, dysbiosis, and non-alcoholic hepatic steatosis, are involved in several molecular and inflammatory mechanisms that alter the metabolism. Food habit changes, such as the quality of fatty acids in the diet, are proposed to treat and prevent these disorders. Some studies demonstrated that saturated fatty acids (SFA) are considered detrimental for treating these disorders. A high fat diet rich in palmitic acid, a SFA, is associated with lower insulin sensitivity and it may also increase atherosclerosis parameters. On the other hand, a high intake of eicosapentaenoic (EPA) and docosahexaenoic (DHA) fatty acids may promote positive effects, especially on triglyceride levels and increased high-density lipoprotein (HDL) levels. Moreover, polyunsaturated fatty acids (PUFAs) and monounsaturated fatty acids (MUFAs) are effective at limiting the hepatic steatosis process through a series of biochemical events, such as reducing the markers of non-alcoholic hepatic steatosis, increasing the gene expression of lipid metabolism, decreasing lipogenic activity, and releasing adiponectin. This current review shows that the consumption of unsaturated fatty acids, MUFA, and PUFA, and especially EPA and DHA, which can be applied as food supplements, may promote effects on glucose and lipid metabolism, as well as on metabolic inflammation, gut microbiota, and hepatic metabolism. PMID:29065507

  20. An integrated model of cardiac mitochondrial energy metabolism and calcium dynamics.

    PubMed

    Cortassa, Sonia; Aon, Miguel A; Marbán, Eduardo; Winslow, Raimond L; O'Rourke, Brian

    2003-04-01

    We present an integrated thermokinetic model describing control of cardiac mitochondrial bioenergetics. The model describes the tricarboxylic acid (TCA) cycle, oxidative phosphorylation, and mitochondrial Ca(2+) handling. The kinetic component of the model includes effectors of the TCA cycle enzymes regulating production of NADH and FADH(2), which in turn are used by the electron transport chain to establish a proton motive force (Delta mu(H)), driving the F(1)F(0)-ATPase. In addition, mitochondrial matrix Ca(2+), determined by Ca(2+) uniporter and Na(+)/Ca(2+) exchanger activities, regulates activity of the TCA cycle enzymes isocitrate dehydrogenase and alpha-ketoglutarate dehydrogenase. The model is described by twelve ordinary differential equations for the time rate of change of mitochondrial membrane potential (Delta Psi(m)), and matrix concentrations of Ca(2+), NADH, ADP, and TCA cycle intermediates. The model is used to predict the response of mitochondria to changes in substrate delivery, metabolic inhibition, the rate of adenine nucleotide exchange, and Ca(2+). The model is able to reproduce, qualitatively and semiquantitatively, experimental data concerning mitochondrial bioenergetics, Ca(2+) dynamics, and respiratory control. Significant increases in oxygen consumption (V(O(2))), proton efflux, NADH, and ATP synthesis, in response to an increase in cytoplasmic Ca(2+), are obtained when the Ca(2+)-sensitive dehydrogenases are the main rate-controlling steps of respiratory flux. These responses diminished when control is shifted downstream (e.g., the respiratory chain or adenine nucleotide translocator). The time-dependent behavior of the model, under conditions simulating an increase in workload, closely reproduces experimentally observed mitochondrial NADH dynamics in heart trabeculae subjected to changes in pacing frequency. The steady-state and time-dependent behavior of the model support the hypothesis that mitochondrial matrix Ca(2+) plays an

  1. An Integrated Model of Cardiac Mitochondrial Energy Metabolism and Calcium Dynamics

    PubMed Central

    Cortassa, Sonia; Aon, Miguel A.; Marbán, Eduardo; Winslow, Raimond L.; O'Rourke, Brian

    2003-01-01

    We present an integrated thermokinetic model describing control of cardiac mitochondrial bioenergetics. The model describes the tricarboxylic acid (TCA) cycle, oxidative phosphorylation, and mitochondrial Ca2+ handling. The kinetic component of the model includes effectors of the TCA cycle enzymes regulating production of NADH and FADH2, which in turn are used by the electron transport chain to establish a proton motive force (ΔμH), driving the F1F0-ATPase. In addition, mitochondrial matrix Ca2+, determined by Ca2+ uniporter and Na+/Ca2+ exchanger activities, regulates activity of the TCA cycle enzymes isocitrate dehydrogenase and α-ketoglutarate dehydrogenase. The model is described by twelve ordinary differential equations for the time rate of change of mitochondrial membrane potential (ΔΨm), and matrix concentrations of Ca2+, NADH, ADP, and TCA cycle intermediates. The model is used to predict the response of mitochondria to changes in substrate delivery, metabolic inhibition, the rate of adenine nucleotide exchange, and Ca2+. The model is able to reproduce, qualitatively and semiquantitatively, experimental data concerning mitochondrial bioenergetics, Ca2+ dynamics, and respiratory control. Significant increases in oxygen consumption (VO2), proton efflux, NADH, and ATP synthesis, in response to an increase in cytoplasmic Ca2+, are obtained when the Ca2+-sensitive dehydrogenases are the main rate-controlling steps of respiratory flux. These responses diminished when control is shifted downstream (e.g., the respiratory chain or adenine nucleotide translocator). The time-dependent behavior of the model, under conditions simulating an increase in workload, closely reproduces experimentally observed mitochondrial NADH dynamics in heart trabeculae subjected to changes in pacing frequency. The steady-state and time-dependent behavior of the model support the hypothesis that mitochondrial matrix Ca2+ plays an important role in matching energy supply with demand in

  2. Bisphenol A effects on gene expression in adipocytes from children: association with metabolic disorders.

    PubMed

    Menale, Ciro; Piccolo, Maria Teresa; Cirillo, Grazia; Calogero, Raffaele A; Papparella, Alfonso; Mita, Luigi; Del Giudice, Emanuele Miraglia; Diano, Nadia; Crispi, Stefania; Mita, Damiano Gustavo

    2015-06-01

    Bisphenol A (BPA) is a xenobiotic endocrine-disrupting chemical. In vitro and in vivo studies have indicated that BPA alters endocrine-metabolic pathways in adipose tissue, which increases the risk of metabolic disorders and obesity. BPA can affect adipose tissue and increase fat cell numbers or sizes by regulating the expression of the genes that are directly involved in metabolic homeostasis and obesity. Several studies performed in animal models have accounted for an obesogen role of BPA, but its effects on human adipocytes - especially in children - have been poorly investigated. The aim of this study is to understand the molecular mechanisms by which environmentally relevant doses of BPA can interfere with the canonical endocrine function that regulates metabolism in mature human adipocytes from prepubertal, non-obese children. BPA can act as an estrogen agonist or antagonist depending on the physiological context. To identify the molecular signatures associated with metabolism, transcriptional modifications of mature adipocytes from prepubertal children exposed to estrogen were evaluated by means of microarray analysis. The analysis of deregulated genes associated with metabolic disorders allowed us to identify a small group of genes that are expressed in an opposite manner from that of adipocytes treated with BPA. In particular, we found that BPA increases the expression of pro-inflammatory cytokines and the expression of FABP4 and CD36, two genes involved in lipid metabolism. In addition, BPA decreases the expression of PCSK1, a gene involved in insulin production. These results indicate that exposure to BPA may be an important risk factor for developing metabolic disorders that are involved in childhood metabolism dysregulation. © 2015 Society for Endocrinology.

  3. Interleukin-22 alleviates metabolic disorders and restores mucosal immunity in diabetes.

    PubMed

    Wang, Xiaoting; Ota, Naruhisa; Manzanillo, Paolo; Kates, Lance; Zavala-Solorio, Jose; Eidenschenk, Celine; Zhang, Juan; Lesch, Justin; Lee, Wyne P; Ross, Jed; Diehl, Lauri; van Bruggen, Nicholas; Kolumam, Ganesh; Ouyang, Wenjun

    2014-10-09

    The connection between an altered gut microbiota and metabolic disorders such as obesity, diabetes, and cardiovascular disease is well established. Defects in preserving the integrity of the mucosal barriers can result in systemic endotoxaemia that contributes to chronic low-grade inflammation, which further promotes the development of metabolic syndrome. Interleukin (IL)-22 exerts essential roles in eliciting antimicrobial immunity and maintaining mucosal barrier integrity within the intestine. Here we investigate the connection between IL-22 and metabolic disorders. We find that the induction of IL-22 from innate lymphoid cells and CD4(+) T cells is impaired in obese mice under various immune challenges, especially in the colon during infection with Citrobacter rodentium. While innate lymphoid cell populations are largely intact in obese mice, the upregulation of IL-23, a cytokine upstream of IL-22, is compromised during the infection. Consequently, these mice are susceptible to C. rodentium infection, and both exogenous IL-22 and IL-23 are able to restore the mucosal host defence. Importantly, we further unveil unexpected functions of IL-22 in regulating metabolism. Mice deficient in IL-22 receptor and fed with high-fat diet are prone to developing metabolic disorders. Strikingly, administration of exogenous IL-22 in genetically obese leptin-receptor-deficient (db/db) mice and mice fed with high-fat diet reverses many of the metabolic symptoms, including hyperglycaemia and insulin resistance. IL-22 shows diverse metabolic benefits, as it improves insulin sensitivity, preserves gut mucosal barrier and endocrine functions, decreases endotoxaemia and chronic inflammation, and regulates lipid metabolism in liver and adipose tissues. In summary, we identify the IL-22 pathway as a novel target for therapeutic intervention in metabolic diseases.

  4. Metabolic screening and metabolomics analysis in the Intellectual Developmental Disorders Mexico Study.

    PubMed

    Ibarra-González, Isabel; Rodríguez-Valentín, Rocío; Lazcano-Ponce, Eduardo; Vela-Amieva, Marcela

    2017-01-01

    Inborn errors of metabolism (IEM) are genetic conditions that are sometimes associated with intellectual developmental disorders (IDD). The aim of this study is to contribute to the metabolic characterization of IDD of unknown etiology in Mexico. Metabolic screening using tandem mass spectrometry and fluorometry will be performed to rule out IEM. In addition, target metabolomic analysis will be done to characterize the metabolomic profile of patients with IDD. Identification of new metabolomic profiles associated with IDD of unknown etiology and comorbidities will contribute to the development of novel diagnostic and therapeutic schemes for the prevention and treatment of IDD in Mexico.

  5. Metabolic disorders in vertigo, tinnitus, and hearing loss.

    PubMed

    Kaźmierczak, H; Doroszewska, G

    2001-01-01

    Vertigo, tinnitus, and hearing loss are common complaints among populations of industrial countries, especially in persons older than 40 years. Numerous agents are known to incite vertigo, tinnitus, and hearing loss, among them hyperinsulinemia, diabetes mellitus, and hyperlipidemia. In this study, we proposed to assess the occurrence of hyperinsulinemia, diabetes mellitus, and hyperlipidemia in patients suffering from vertigo, tinnitus, or hearing loss of unknown origin. Results of various tests in 48 patients were compared to those in 31 control subjects. Assessments of body mass index, blood pressure, and laryngological, audiometric, and electronystagmographic parameters were performed in all study participants. An oral glucose tolerance test was used to evaluate insulin levels, and lipoprotein phenotyping served to determine cholesterol, triglyceride, and lipoprotein levels. Patients were found to be significantly more overweight (on the basis of body mass index) than were the control subjects. Hypertension was more common among patients than controls, but the difference was significant only between the men in the two groups. Disturbances of glucose metabolism were found in 27.1% of patients but in only 9.7% of controls. Diabetes mellitus was not present in any controls but was identified in four patients. Hyperinsulinemia was almost twice as common in patients as in controls. Only the occurrence of hyperlipoproteinemia seemed not to differ between patients and control subjects. We conclude that such disturbances of glucose metabolism as diabetes mellitus and hyperinsulinemia may be responsible for inner ear diseases, whereas the role of disturbances of lipid metabolism remains vague.

  6. Role of MicroRNAs in Obesity-Induced Metabolic Disorder and Immune Response.

    PubMed

    Zhong, Hong; Ma, Minjuan; Liang, Tingming; Guo, Li

    2018-01-01

    In all living organisms, metabolic homeostasis and the immune system are the most fundamental requirements for survival. Recently, obesity has become a global public health issue, which is the cardinal risk factor for metabolic disorder. Many diseases emanating from obesity-induced metabolic dysfunction are responsible for the activated immune system, including innate and adaptive responses. Of note, inflammation is the manifest accountant signal. Deeply studied microRNAs (miRNAs) have participated in many pathways involved in metabolism and immune responses to protect cells from multiple harmful stimulants, and they play an important role in determining the progress through targeting different inflammatory pathways. Thus, immune response and metabolic regulation are highly integrated with miRNAs. Collectively, miRNAs are the new targets for therapy in immune dysfunction.

  7. Role of MicroRNAs in Obesity-Induced Metabolic Disorder and Immune Response

    PubMed Central

    Zhong, Hong; Ma, Minjuan

    2018-01-01

    In all living organisms, metabolic homeostasis and the immune system are the most fundamental requirements for survival. Recently, obesity has become a global public health issue, which is the cardinal risk factor for metabolic disorder. Many diseases emanating from obesity-induced metabolic dysfunction are responsible for the activated immune system, including innate and adaptive responses. Of note, inflammation is the manifest accountant signal. Deeply studied microRNAs (miRNAs) have participated in many pathways involved in metabolism and immune responses to protect cells from multiple harmful stimulants, and they play an important role in determining the progress through targeting different inflammatory pathways. Thus, immune response and metabolic regulation are highly integrated with miRNAs. Collectively, miRNAs are the new targets for therapy in immune dysfunction. PMID:29484304

  8. Posttraumatic Stress Disorder, Cardiovascular and Metabolic Disease: A Review of the Evidence

    PubMed Central

    Dedert, Eric A.; Calhoun, Patrick S.; Watkins, Lana L.; Sherwood, Andrew; Beckham, Jean C.

    2011-01-01

    Background Posttraumatic stress disorder (PTSD) is a significant risk factor for cardiovascular and metabolic disease. Purpose The purpose of the current review is to evaluate the evidence suggesting that PTSD increases cardiovascular and metabolic risk factors, and to identify possible biomarkers and psychosocial characteristics and behavioral variables that are associated with these outcomes. Methods A systematic literature search in the period of 2002–2009 for PTSD, cardiovascular disease, and metabolic disease was conducted. Results The literature search yielded 78 studies on PTSD and cardiovascular/metabolic disease and biomarkers. Conclusions Although the available literature suggests an association of PTSD with cardiovascular disease and biomarkers, further research must consider potential confounds, incorporate longitudinal designs, and conduct careful PTSD assessments in diverse samples to address gaps in the research literature. Research on metabolic disease and biomarkers suggests an association with PTSD, but has not progressed as far as the cardiovascular research. PMID:20174903

  9. Lipoprotein (a), metabolic syndrome and coronary calcium score in a large occupational cohort.

    PubMed

    Sung, K-C; Wild, S H; Byrne, C D

    2013-12-01

    Whether lipoprotein (a) [Lp(a)] concentration is associated with metabolic syndrome (MetS) and pre-clinical atherosclerosis in different ethnic groups is uncertain. The association between Lp(a), MetS and a measure of pre-clinical atherosclerosis was studied in a large Asian cohort. Data were analyzed from a South Korean occupational cohort who underwent a cardiac computed tomography (CT) estimation of CAC score and measurements of cardiovascular risk factors (n = 14,583 people). The key exposure was an Lp(a) concentration in the top quartile (>38.64 mg/dL)) with a CAC score >0 as the outcome variable and measure of pre-clinical atherosclerosis. Logistic regression was used to describe the associations. 1462 participants had a CAC score >0. In the lowest Lp(a) quartile (<11.29 mg/dL), 25.8% had MetS, compared with 16.1% in the highest Lp(a) quartile (>38.64 mg/dL (p < 0.001). MetS, and component features, were inversely related to Lp(a) concentration (all p < 0.0001). In the highest Lp(a) quartile group, there was an association between Lp(a) and CAC score >0 in men (OR 1.21[1.05, 1.40], p = 0.008), and women (OR 1.62[1.03, 2.55], p = 0.038), after adjustment for age, sex, lipid lowering therapy, and multiple cardiovascular risk factors. There was no evidence of an interaction between highest quartile Lp(a) and either high LDLc (>147 mg/dL) (p = 0.99), or MetS (p = 0.84) on the association with CAC score >0. Lp(a) levels are inversely related to MetS and its components. There was a robust association between Lp(a) concentration >38.6 mg/dL and marker of early atherosclerosis in both men and women, regardless of LDLc, level MetS or other cardiovascular risk factors. © 2013 Elsevier B.V. All rights reserved.

  10. Association between vitamin deficiency and metabolic disorders related to obesity.

    PubMed

    Thomas-Valdés, Samanta; Tostes, Maria das Graças V; Anunciação, Pamella C; da Silva, Bárbara P; Sant'Ana, Helena M Pinheiro

    2017-10-13

    Inappropriate food behavior contributes to obesity and leads to vitamin deficiency. This review discusses the nutritional status of water- and fat-soluble vitamins in obese subjects. We verified that most vitamins are deficient in obese individuals, especially the fat-soluble vitamins, folic acid, vitamin B 12 and vitamin C. However, some vitamins have been less evaluated in cases of obesity. The adipose tissue is considered a metabolic and endocrine organ, which in excess leads to changes in body homeostasis, as well as vitamin deficiency which can aggravate the pathological state. Therefore, the evaluation of vitamin status is of fundamental importance in obese individuals.

  11. Markers of bone resorption and calcium metabolism are related to dietary intake patterns in male and female bed rest subjects

    NASA Technical Reports Server (NTRS)

    Smith, Scott M.; Zwart, S. R.; Hargens, A. r.

    2006-01-01

    Dietary potassium and protein intakes predict net endogenous acid production in humans. Intracellular buffers, including exchangeable bone mineral, play a crucial role in balancing chronic acid-base perturbations in the body; subsequently, chronic acid loads can potentially contribute to bone loss. Bone is lost during space flight, and a dietary countermeasure would be desirable for many reasons. We studied the ability of diet protein and potassium to predict levels of bone resorption markers in males and females. Identical twin pairs (8 M, 7 F) were assigned to 2 groups: bed rest (sedentary, SED) or bed rest with supine treadmill exercise in a lower body negative pressure chamber (EX). Diet was controlled for 3 d before and 30 d of bed rest (BR). Urinary Ca, N-telopeptide (NTX), and pyridinium crosslinks (PYD) were measured before and on days 5, 12, 19, and 26 of BR. Data were analyzed by Pearson correlation (P<0.05). The ratio of dietary animal protein/potassium intake was not correlated with NTX before BR for males or females, but they were positively correlated in both groups of males during bed rest. Dietary animal protein/potassium and urine Ca were correlated before and during bed rest for the males, and only during bed rest for the females. Conversely, the ratio of dietary vegetable protein/potassium intake was negatively correlated with urinary calcium during bed rest for the females, but there was no relationship between vegetable protein/potassium intake and bone markers for the males. These data suggest that the ratio of animal protein/potassium intake may affect bone, particularly in bed rest subjects. These data show that the type of protein and gender may be additional factors that modulate the effect of diet on bone metabolism during bed rest. Altering this ratio may help prevent bone loss on Earth and during space flight.

  12. Stimulation of fibroblast growth factor 23 by metabolic acidosis requires osteoblastic intracellular calcium signaling and prostaglandin synthesis.

    PubMed

    Krieger, Nancy S; Bushinsky, David A

    2017-10-01

    Serum fibroblast growth factor 23 (FGF23) increases progressively in chronic kidney disease (CKD) and is associated with increased mortality. FGF23 is synthesized in osteoblasts and osteocytes; however, the factors regulating its production are not clear. Patients with CKD have decreased renal acid excretion leading to metabolic acidosis (MET). During MET, acid is buffered by bone with release of mineral calcium (Ca) and phosphate (P). MET increases intracellular Ca signaling and cyclooxygenase 2 (COX2)-induced prostaglandin production in the osteoblast, leading to decreased bone formation and increased bone resorption. We found that MET directly stimulates FGF23 in mouse bone organ cultures and primary osteoblasts. We hypothesized that MET increases FGF23 through similar pathways that lead to bone resorption. Neonatal mouse calvariae were incubated in neutral (NTL, pH = 7.44, Pco 2 = 38 mmHg, [HCO 3 - ] = 27 mM) or acid (MET, pH = 7.18, Pco 2 = 37 mmHg, [HCO 3 - ] = 13 mM) medium without or with 2-APB (50 μM), an inhibitor of intracellular Ca signaling or NS-398 (1 μM), an inhibitor of COX2. Each agent significantly inhibited MET stimulation of medium FGF23 protein and calvarial FGF23 RNA as well as bone resorption at 48 h. To exclude the potential contribution of MET-induced bone P release, we utilized primary calvarial osteoblasts. In these cells each agent inhibited MET stimulation of FGF23 RNA expression at 6 h. Thus stimulation of FGF23 by MET in mouse osteoblasts utilizes the same initial signaling pathways as MET-induced bone resorption. Therapeutic interventions directed toward correction of MET, especially in CKD, have the potential to not only prevent bone resorption but also lower FGF23 and perhaps decrease mortality. Copyright © 2017 the American Physiological Society.

  13. Consistent abnormalities in metabolic network activity in idiopathic rapid eye movement sleep behaviour disorder.

    PubMed

    Wu, Ping; Yu, Huan; Peng, Shichun; Dauvilliers, Yves; Wang, Jian; Ge, Jingjie; Zhang, Huiwei; Eidelberg, David; Ma, Yilong; Zuo, Chuantao

    2014-12-01

    Rapid eye movement sleep behaviour disorder has been evaluated using Parkinson's disease-related metabolic network. It is unknown whether this disorder is itself associated with a unique metabolic network. 18F-fluorodeoxyglucose positron emission tomography was performed in 21 patients (age 65.0±5.6 years) with idiopathic rapid eye movement sleep behaviour disorder and 21 age/gender-matched healthy control subjects (age 62.5±7.5 years) to identify a disease-related pattern and examine its evolution in 21 hemi-parkinsonian patients (age 62.6±5.0 years) and 16 moderate parkinsonian patients (age 56.9±12.2 years). We identified a rapid eye movement sleep behaviour disorder-related metabolic network characterized by increased activity in pons, thalamus, medial frontal and sensorimotor areas, hippocampus, supramarginal and inferior temporal gyri, and posterior cerebellum, with decreased activity in occipital and superior temporal regions. Compared to the healthy control subjects, network expressions were elevated (P<0.0001) in the patients with this disorder and in the parkinsonian cohorts but decreased with disease progression. Parkinson's disease-related network activity was also elevated (P<0.0001) in the patients with rapid eye movement sleep behaviour disorder but lower than in the hemi-parkinsonian cohort. Abnormal metabolic networks may provide markers of idiopathic rapid eye movement sleep behaviour disorder to identify those at higher risk to develop neurodegenerative parkinsonism. © The Author (2014). Published by Oxford University Press on behalf of the Guarantors of Brain. All rights reserved. For Permissions, please email: journals.permissions@oup.com.

  14. [Therapeutic agents for disorders of bone and calcium metabolism--Parathyroid hormone in weekly subcutaneous injection].

    PubMed

    Uzawa, Toyonobu

    2007-01-01

    The parathyroid hormone (PTH) that is marketed outside Japan is for daily administration. It has been proven to increase bone mass and prevent fractures, and the effects are very strong. However, data suggest that daily administration of PTH increases bone resorption. By contrast, weekly administration of PTH, which is being developed in Japan, actually decreases bone resorption, and data suggest that this regimen maintains a good balance between bone formation (predominant) and bone resorption. Furthermore, it has been reported that weekly administration of PTH increases bone mass as much as every day administration of PTH, and as such, weekly administration of PTH has the potential to be a useful regimen with characteristics that are different from those of daily administration of PTH.

  15. Systems Nutrigenomics Reveals Brain Gene Networks Linking Metabolic and Brain Disorders.

    PubMed

    Meng, Qingying; Ying, Zhe; Noble, Emily; Zhao, Yuqi; Agrawal, Rahul; Mikhail, Andrew; Zhuang, Yumei; Tyagi, Ethika; Zhang, Qing; Lee, Jae-Hyung; Morselli, Marco; Orozco, Luz; Guo, Weilong; Kilts, Tina M; Zhu, Jun; Zhang, Bin; Pellegrini, Matteo; Xiao, Xinshu; Young, Marian F; Gomez-Pinilla, Fernando; Yang, Xia

    2016-05-01

    Nutrition plays a significant role in the increasing prevalence of metabolic and brain disorders. Here we employ systems nutrigenomics to scrutinize the genomic bases of nutrient-host interaction underlying disease predisposition or therapeutic potential. We conducted transcriptome and epigenome sequencing of hypothalamus (metabolic control) and hippocampus (cognitive processing) from a rodent model of fructose consumption, and identified significant reprogramming of DNA methylation, transcript abundance, alternative splicing, and gene networks governing cell metabolism, cell communication, inflammation, and neuronal signaling. These signals converged with genetic causal risks of metabolic, neurological, and psychiatric disorders revealed in humans. Gene network modeling uncovered the extracellular matrix genes Bgn and Fmod as main orchestrators of the effects of fructose, as validated using two knockout mouse models. We further demonstrate that an omega-3 fatty acid, DHA, reverses the genomic and network perturbations elicited by fructose, providing molecular support for nutritional interventions to counteract diet-induced metabolic and brain disorders. Our integrative approach complementing rodent and human studies supports the applicability of nutrigenomics principles to predict disease susceptibility and to guide personalized medicine. Copyright © 2016 The Authors. Published by Elsevier B.V. All rights reserved.

  16. Red-koji fermented red ginseng ameliorates high fat diet-induced metabolic disorders in mice.

    PubMed

    Kim, Chang Man; Yi, Seong Joon; Cho, Il Je; Ku, Sae Kwang

    2013-10-30

    Fermentation of medicinal herbs improves their pharmacological efficacy. In this study, we investigated the effects of red-koji fermented red ginseng (fRG) on high-fat diet (HFD)-mediated metabolic disorders, and those effects were compared to those of non-fermented red ginseng (RG). fRG (500, 250 or 125 mg/kg), RG (250 mg/kg), simvastatin (10 mg/kg), silymarin (100 mg/kg) and metformin (250 mg/kg) were orally administered from 1 week after initiation of HFD supply for 84 days. The diameter of adipocytes in periovarian and abdominal fat pads and the thickness of the abdominal fat were significantly decreased by fRG treatment, while HFD-mediated weight gain was partly alleviated by fRG in a dose-dependent manner. Moreover, biochemical and histomorphometrical analyses clearly indicated that fRG significantly inhibited HFD-induced metabolic disorders such as hyperglycemia, hyperlipidemia, hepatopathy and nephropathy in a dose-dependent manner. More favorable pharmacological effects on HFD-mediated metabolic disorders were also observed with fRG compared to an equal dose of RG. This finding provides direct evidence that the pharmacological activities of RG were enhanced by red-koji fermentation, and fRG could be a neutraceutical resource for the alleviation of obesity-mediated metabolic disorders.

  17. Regional cerebral glucose metabolism in systemic lupus erythematosus patients with major depressive disorder.

    PubMed

    Saito, Tomoyuki; Tamura, Maasa; Chiba, Yuhei; Katsuse, Omi; Suda, Akira; Kamada, Ayuko; Ikura, Takahiro; Abe, Kie; Ogawa, Matsuyoshi; Minegishi, Kaoru; Yoshimi, Ryusuke; Kirino, Yohei; Ihata, Atsushi; Hirayasu, Yoshio

    2017-08-15

    Depression is frequently observed in patients with systemic lupus erythematosus (SLE). Neuropsychiatric SLE (NPSLE) patients often exhibit cerebral hypometabolism, but the association between cerebral metabolism and depression remains unclear. To elucidate the features of cerebral metabolism in SLE patients with depression, we performed brain 18F-fluoro-d-glucose positron emission tomography (FDG-PET) on SLE patients with and without major depressive disorder. We performed brain FDG-PET on 20 SLE subjects (5 male, 15 female). The subjects were divided into two groups: subjects with major depressive disorder (DSLE) and subjects without major depressive disorder (non-DSLE). Cerebral glucose metabolism was analyzed using the three-dimensional stereotactic surface projection (3D-SSP) program. Regional metabolism was evaluated by stereotactic extraction estimation (SEE), in which the whole brain was divided into segments. Every SLE subject exhibited cerebral hypometabolism, in contrast to the normal healthy subjects. Regional analysis revealed a significantly lower ER in the left medial frontal gyrus (p=0.0055) and the right medial frontal gyrus (p=0.0022) in the DSLE group than in the non-DSLE group. Hypometabolism in the medial frontal gyrus may be related to major depressive disorder in SLE. Larger studies are needed to clarify this relationship. Copyright © 2017 Elsevier B.V. All rights reserved.

  18. Drug correction of behavioral reactions and metabolic disorders in rats with craniocerebral trauma.

    PubMed

    Zarubina, I V

    2003-07-01

    Intraperitoneal injection of bemithyl in a dose of 25 mg/kg for 3 days after craniocerebral injury reduced psychopathological symptoms in rats with different resistance to acute hypoxia, restored the structure of individual behavior, and prevented metabolic disorders in the brain.

  19. Lower urinary tract symptoms and metabolic disorders: ICI-RS 2014.

    PubMed

    Denys, Marie-Astrid; Anding, Ralf; Tubaro, Andrea; Abrams, Paul; Everaert, Karel

    2016-02-01

    To investigate the link between lower urinary tract symptoms (LUTS) and metabolic disorders. This report results from presentations and subsequent discussions about LUTS and metabolic disorders at the International Consultation on Incontinence Research Society (ICI-RS) in Bristol, 2014. There are common pathophysiological determinants for the onset of LUTS and the metabolic syndrome (MetS). Both conditions are multifactorial, related to disorders in circadian rhythms and share common risk factors. As in men with erectile dysfunction, these potentially modifiable lifestyle factors may be novel targets to prevent and treat LUTS. The link between LUTS and metabolic disorders is discussed by using sleep, urine production and bladder function as underlying mechanisms that need to be further explored during future research. Recent findings indicate a bidirectional relationship between LUTS and the MetS. Future research has to explore underlying mechanisms to explain this relationship, in order to develop new preventive and therapeutic recommendations, such as weight loss and increasing physical activity. The second stage is to determine the effect of these new treatment approaches on the severity of LUTS and each of the components of the MetS. © 2016 Wiley Periodicals, Inc.

  20. Insurance coverage of medical foods for treatment of inherited metabolic disorders

    PubMed Central

    Berry, Susan A.; Kenney, Mary Kay; Harris, Katharine B.; Singh, Rani H.; Cameron, Cynthia A.; Kraszewski, Jennifer N.; Levy-Fisch, Jill; Shuger, Jill F.; Greene, Carol L.; Lloyd-Puryear, Michele A.; Boyle, Coleen A.

    2015-01-01

    Purpose Treatment of inherited metabolic disorders is accomplished by use of specialized diets employing medical foods and medically necessary supplements. Families seeking insurance coverage for these products express concern that coverage is often limited; the extent of this challenge is not well defined. Methods To learn about limitations in insurance coverage, parents of 305 children with inherited metabolic disorders completed a paper survey providing information about their use of medical foods, modified low-protein foods, prescribed dietary supplements, and medical feeding equipment and supplies for treatment of their child's disorder as well as details about payment sources for these products. Results Although nearly all children with inherited metabolic dis orders had medical coverage of some type, families paid “out of pocket” for all types of products. Uncovered spending was reported for 11% of families purchasing medical foods, 26% purchasing supplements, 33% of those needing medical feeding supplies, and 59% of families requiring modified low-protein foods. Forty-two percent of families using modified low-protein foods and 21% of families using medical foods reported additional treatment-related expenses of $100 or more per month for these products. Conclusion Costs of medical foods used to treat inherited metabolic disorders are not completely covered by insurance or other resources. PMID:23598714

  1. Should Metabolic Diseases Be Systematically Screened in Nonsyndromic Autism Spectrum Disorders?

    PubMed Central

    Schiff, Manuel; Benoist, Jean-François; Aïssaoui, Sofiane; Boepsflug-Tanguy, Odile; Mouren, Marie-Christine; de Baulny, Hélène Ogier; Delorme, Richard

    2011-01-01

    Background In the investigation of autism spectrum disorders (ASD), a genetic cause is found in approximately 10–20%. Among these cases, the prevalence of the rare inherited metabolic disorders (IMD) is unknown and poorly evaluated. An IMD responsible for ASD is usually identified by the associated clinical phenotype such as dysmorphic features, ataxia, microcephaly, epilepsy, and severe intellectual disability (ID). In rare cases, however, ASD may be considered as nonsyndromic at the onset of a related IMD. Objectives To evaluate the utility of routine metabolic investigations in nonsyndromic ASD. Patients and Methods We retrospectively analyzed the results of a metabolic workup (urinary mucopolysaccharides, urinary purines and pyrimidines, urinary creatine and guanidinoacetate, urinary organic acids, plasma and urinary amino acids) routinely performed in 274 nonsyndromic ASD children. Results The metabolic parameters were in the normal range for all but 2 patients: one with unspecific creatine urinary excretion and the other with persistent 3-methylglutaconic aciduria. Conclusions These data provide the largest ever reported cohort of ASD patients for whom a systematic metabolic workup has been performed; they suggest that such a routine metabolic screening does not contribute to the causative diagnosis of nonsyndromic ASD. They also emphasize that the prevalence of screened IMD in nonsyndromic ASD is probably not higher than in the general population (<0.5%). A careful clinical evaluation is probably more reasonable and of better medical practice than a costly systematic workup. PMID:21760924

  2. Application of exome sequencing in the search for genetic causes of rare disorders of copper metabolism.

    PubMed

    Fuchs, Sabine A; Harakalova, Magdalena; van Haaften, Gijs; van Hasselt, Peter M; Cuppen, Edwin; Houwen, Roderick H J

    2012-07-01

    The genetic defect in a number of rare disorders of metal metabolism remains elusive. The limited number of patients with these disorders impedes the identification of the causative gene through positional cloning, which requires numerous families with multiple affected individuals. However, with next-generation sequencing all coding DNA (exomes) or whole genomes of patients can be sequenced to identify genes that are consistently mutated in patients. With this strategy only a limited number of patients and/or pedigrees is needed, bringing the elucidation of the genetic cause of even very rare diseases within reach. The main challenge associated with whole exome sequencing is the identification of the disease-causing mutation(s) among abundant genetic candidate variants. We describe several strategies to manage this data wealth, including comparison with control databases, increasing the number of patients and controls, and reducing the genomic region under investigation through homozygosity mapping. In this review we introduce a number of rare disorders of copper metabolism, with a suspected but yet unknown monogenetic cause, as an attractive target for this strategy. We anticipate that use of these novel techniques will identify the basic defect in the disorders described in this review, as well as in other genetic disorders of metal metabolism, in the next few years.

  3. Adaptation of red cell enzymes and intermediates in metabolic disorders.

    PubMed

    Goebel, K M; Goebel, F D; Neitzert, A; Hausmann, L; Schneider, J

    1975-01-01

    The metabolic activity of the red cell glycolytic pathway hexose monophosphate shunt (HMP) with dependent glutathione system was studied in patients with hyperthyroidism (n = 10), hyperlipoproteinemia (n = 16), hypoglycemia (n = 25) and hyperglycemia (n = 23). In uncontrolled diabetics and patients with hyperthyroidism the mean value of glucose phosphate isomerase (GPI), glucose-6-phosphate dehydrogenase (G-6-PD), glutathione reductase (GR) was increased, whereas these enzyme activities were reduced in patients with hypoglycemia. Apart from a few values of hexokinase (HK) which were lower than normal the results in hyperlipoproteinemia patients remained essentially unchanged, including the intermediates such as 2,3-diphosphoglycerate (2,3-DPG), adenosine triphosphate (ATP) and reduced glutathione (GSH). While increased rates of 2,3-DPG and ATP in hypoglycemia patients were obtained, these substrates were markedly reduced in diabetics.

  4. Obesity in dogs and cats: a metabolic and endocrine disorder.

    PubMed

    Zoran, Debra L

    2010-03-01

    Obesity is defined as an accumulation of excessive amounts of adipose tissue in the body, and has been called the most common nutritional disease of dogs in Western countries. Most investigators agree that at least 33% of the dogs presented to veterinary clinics are obese, and that the incidence is increasing as human obesity increases in the overall population. Obesity is not just the accumulation of large amounts of adipose tissue, but is associated with important metabolic and hormonal changes in the body, which are the focus of this review. Obesity is associated with a variety of conditions, including osteoarthritis, respiratory distress, glucose intolerance and diabetes mellitus, hypertension, dystocia, decreased heat tolerance, some forms of cancer, and increased risk of anesthetic and surgical complications. Prevention and early recognition of obesity, as well as correcting obesity when it is present, are essential to appropriate health care, and increases both the quality and quantity of life for pets. Copyright 2010 Elsevier Inc. All rights reserved.

  5. From "Kidneys Govern Bones" to Chronic Kidney Disease, Diabetes Mellitus, and Metabolic Bone Disorder: A Crosstalk between Traditional Chinese Medicine and Modern Science.

    PubMed

    Wang, Xiao-Qin; Zou, Xin-Rong; Zhang, Yuan Clare

    2016-01-01

    Although traditional Chinese medicine (TCM) and Western medicine have evolved on distinct philosophical foundations and reasoning methods, an increasing body of scientific data has begun to reveal commonalities. Emerging scientific evidence has confirmed the validity and identified the molecular mechanisms of many ancient TCM theories. One example is the concept of "Kidneys Govern Bones." Here we discuss the molecular mechanisms supporting this theory and its potential significance in treating complications of chronic kidney disease (CKD) and diabetes mellitus. Two signaling pathways essential for calcium-phosphate metabolism can mediate the effect of kidneys in bone homeostasis, one requiring renal production of bioactive vitamin D and the other involving an endocrine axis based on kidney-expressed Klotho and bone-secreted fibroblast growth factor 23. Disruption of either pathway can lead to calcium-phosphate imbalance and vascular calcification, accelerating metabolic bone disorder. Chinese herbal medicine is an adjunct therapy widely used for treating CKD and diabetes. Our results demonstrate the therapeutic effects and underlying mechanisms of a Chinese herbal formulation, Shen-An extracts, in diabetic nephropathy and renal osteodystrophy. We believe that the smart combination of Eastern and Western concepts holds great promise for inspiring new ideas and therapies for preventing and treating complications of CKD and diabetes.

  6. From “Kidneys Govern Bones” to Chronic Kidney Disease, Diabetes Mellitus, and Metabolic Bone Disorder: A Crosstalk between Traditional Chinese Medicine and Modern Science

    PubMed Central

    Zou, Xin-Rong

    2016-01-01

    Although traditional Chinese medicine (TCM) and Western medicine have evolved on distinct philosophical foundations and reasoning methods, an increasing body of scientific data has begun to reveal commonalities. Emerging scientific evidence has confirmed the validity and identified the molecular mechanisms of many ancient TCM theories. One example is the concept of “Kidneys Govern Bones.” Here we discuss the molecular mechanisms supporting this theory and its potential significance in treating complications of chronic kidney disease (CKD) and diabetes mellitus. Two signaling pathways essential for calcium-phosphate metabolism can mediate the effect of kidneys in bone homeostasis, one requiring renal production of bioactive vitamin D and the other involving an endocrine axis based on kidney-expressed Klotho and bone-secreted fibroblast growth factor 23. Disruption of either pathway can lead to calcium-phosphate imbalance and vascular calcification, accelerating metabolic bone disorder. Chinese herbal medicine is an adjunct therapy widely used for treating CKD and diabetes. Our results demonstrate the therapeutic effects and underlying mechanisms of a Chinese herbal formulation, Shen-An extracts, in diabetic nephropathy and renal osteodystrophy. We believe that the smart combination of Eastern and Western concepts holds great promise for inspiring new ideas and therapies for preventing and treating complications of CKD and diabetes. PMID:27668003

  7. Metabolic Disorders in the Transition Period Indicate that the Dairy Cows’ Ability to Adapt is Overstressed

    PubMed Central

    Sundrum, Albert

    2015-01-01

    Simple Summary Metabolic disorders are a key problem in the transition period of dairy cows and often appear before the onset of further health problems. Problems derive from difficulties animals have to adapt to large variations and disturbances occurring both outside and inside the organism. A lack of success in solving these issues may be due to predominant approaches in farm management and agricultural science, dealing with such disorders as merely negative side effects. Instead, a successful adaptation of animals to their living conditions should be seen as an important end in itself. Both farm management and agricultural sciences should support animals in their ability to cope with nutritional and metabolic challenges by employing a functional and result-driven approach. Abstract Metabolic disorders are a key problem in the transition period of dairy cows and often appear before the onset of further health problems. They mainly derive from difficulties the animals have in adapting to changes and disturbances occurring both outside and inside the organisms and due to varying gaps between nutrient supply and demand. Adaptation is a functional and target-oriented process involving the whole organism and thus cannot be narrowed down to single factors. Most problems which challenge the organisms can be solved in a number of different ways. To understand the mechanisms of adaptation, the interconnectedness of variables and the nutrient flow within a metabolic network need to be considered. Metabolic disorders indicate an overstressed ability to balance input, partitioning and output variables. Dairy cows will more easily succeed in adapting and in avoiding dysfunctional processes in the transition period when the gap between nutrient and energy demands and their supply is restricted. Dairy farms vary widely in relation to the living conditions of the animals. The complexity of nutritional and metabolic processes and their large variations on various scales

  8. Genetic ablation of calcium-independent phospholipase A2gamma leads to alterations in mitochondrial lipid metabolism and function resulting in a deficient mitochondrial bioenergetic phenotype.

    PubMed

    Mancuso, David J; Sims, Harold F; Han, Xianlin; Jenkins, Christopher M; Guan, Shao Ping; Yang, Kui; Moon, Sung Ho; Pietka, Terri; Abumrad, Nada A; Schlesinger, Paul H; Gross, Richard W

    2007-11-30

    Previously, we identified a novel calcium-independent phospholipase, designated calcium-independent phospholipase A(2) gamma (iPLA(2)gamma), which possesses dual mitochondrial and peroxisomal subcellular localization signals. To identify the roles of iPLA(2)gamma in cellular bioenergetics, we generated mice null for the iPLA(2)gamma gene by eliminating the active site of the enzyme through homologous recombination. Mice null for iPLA(2)gamma display multiple bioenergetic dysfunctional phenotypes, including 1) growth retardation, 2) cold intolerance, 3) reduced exercise endurance, 4) greatly increased mortality from cardiac stress after transverse aortic constriction, 5) abnormal mitochondrial function with a 65% decrease in ascorbate-induced Complex IV-mediated oxygen consumption, and 6) a reduction in myocardial cardiolipin content accompanied by an altered cardiolipin molecular species composition. We conclude that iPLA(2)gamma is essential for maintaining efficient bioenergetic mitochondrial function through tailoring mitochondrial membrane lipid metabolism and composition.

  9. Role of melatonin on diabetes-related metabolic disorders

    PubMed Central

    Espino, Javier; Pariente, José A; Rodríguez, Ana B

    2011-01-01

    Melatonin is a circulating hormone that is mainly released from the pineal gland. It is best known as a regulator of seasonal and circadian rhythms, its levels being high during the night and low during the day. Interestingly, insulin levels are also adapted to day/night changes through melatonin-dependent synchronization. This regulation may be explained by the inhibiting action of melatonin on insulin release, which is transmitted through both the pertussis-toxin-sensitive membrane receptors MT1 and MT2 and the second messengers 3’,5’-cyclic adenosine monophosphate, 3’,5’-cyclic guanosine monophosphate and inositol 1,4,5-trisphosphate. Melatonin may influence diabetes and associated metabolic disturbances not only by regulating insulin secretion, but also by providing protection against reactive oxygen species, since pancreatic β-cells are very susceptible to oxidative stress because they possess only low-antioxidative capacity. On the other hand, in several genetic association studies, single nucleotide polymorphysms of the human MT2 receptor have been described as being causally linked to an elevated risk of developing type 2 diabetes. This suggests that these individuals may be more sensitive to the actions of melatonin, thereby leading to impaired insulin secretion. Therefore, blocking the melatonin-induced inhibition of insulin secretion may be a novel therapeutic avenue for type 2 diabetes. PMID:21860691

  10. The role of genetic variation of human metabolism for BMI, mental traits and mental disorders.

    PubMed

    Hebebrand, Johannes; Peters, Triinu; Schijven, Dick; Hebebrand, Moritz; Grasemann, Corinna; Winkler, Thomas W; Heid, Iris M; Antel, Jochen; Föcker, Manuel; Tegeler, Lisa; Brauner, Lena; Adan, Roger A H; Luykx, Jurjen J; Correll, Christoph U; König, Inke R; Hinney, Anke; Libuda, Lars

    2018-06-01

    The aim was to assess whether loci associated with metabolic traits also have a significant role in BMI and mental traits/disorders METHODS: We first assessed the number of single nucleotide polymorphisms (SNPs) with genome-wide significance for human metabolism (NHGRI-EBI Catalog). These 516 SNPs (216 independent loci) were looked-up in genome-wide association studies for association with body mass index (BMI) and the mental traits/disorders educational attainment, neuroticism, schizophrenia, well-being, anxiety, depressive symptoms, major depressive disorder, autism-spectrum disorder, attention-deficit/hyperactivity disorder, Alzheimer's disease, bipolar disorder, aggressive behavior, and internalizing problems. A strict significance threshold of p < 6.92 × 10 -6 was based on the correction for 516 SNPs and all 14 phenotypes, a second less conservative threshold (p < 9.69 × 10 -5 ) on the correction for the 516 SNPs only. 19 SNPs located in nine independent loci revealed p-values < 6.92 × 10 -6 ; the less strict criterion was met by 41 SNPs in 24 independent loci. BMI and schizophrenia showed the most pronounced genetic overlap with human metabolism with three loci each meeting the strict significance threshold. Overall, genetic variation associated with estimated glomerular filtration rate showed up frequently; single metabolite SNPs were associated with more than one phenotype. Replications in independent samples were obtained for BMI and educational attainment. Approximately 5-10% of the regions involved in the regulation of blood/urine metabolite levels seem to also play a role in BMI and mental traits/disorders and related phenotypes. If validated in metabolomic studies of the respective phenotypes, the associated blood/urine metabolites may enable novel preventive and therapeutic strategies. Copyright © 2018 The Authors. Published by Elsevier GmbH.. All rights reserved.

  11. [Consensus statement on metabolic disorders and cardiovascular risks in patients with human immunodeficiency virus].

    PubMed

    Polo Rodríguez, Rosa; Galindo Puerto, María José; Dueñas, Carlos; Gómez Candela, Carmen; Estrada, Vicente; Villar, Noemí G P; Locutura, Jaime; Mariño, Ana; Pascua, Javier; Palacios, Rosario; von Wichmman, Miguel Ángel; Álvarez, Julia; Asensi, Victor; Lopez Aldeguer, José; Lozano, Fernando; Negredo, Eugenia; Ortega, Enrique; Pedrol, Enric; Gutiérrez, Félix; Sanz Sanz, Jesús; Martínez Chamorro, Esteban

    2015-01-01

    This consensus document is an update of metabolic disorders and cardiovascular risk (CVR) guidelines for HIV-infected patients. This document has been approved by an expert panel of GEAM, SPNS and GESIDA after reviewing the results of efficacy and safety of clinical trials, cohort and pharmacokinetic studies published in biomedical journals (PubMed and Embase) or presented in medical scientific meetings. Recommendation strength and the evidence in which they are supported are based on the GRADE system. A healthy lifestyle is recommended, no smoking and at least 30min of aerobic exercise daily. In diabetic patients the same treatment as non-HIV infected patients is recommended. HIV patients with dyslipidemia should be considered as high CVR, thus its therapeutic objective is an LDL less than 100mg/dL. The antihypertensive of ACE inhibitors and ARAII families are better tolerated and have a lower risk of interactions. In HIV-patients with diabetes or metabolic syndrome and elevated transaminases with no defined etiology, the recommended is to rule out a hepatic steatosis Recommendations for action in hormone alterations are also updated. These new guidelines update previous recommendations regarding all those metabolic disorders involved in CVR. Hormone changes and their management and the impact of metabolic disorders on the liver are also included. Copyright © 2014 Elsevier España, S.L.U. y Sociedad Española de Enfermedades Infecciosas y Microbiología Clínica. All rights reserved.

  12. Lipid metabolism in myelinating glial cells: lessons from human inherited disorders and mouse models.

    PubMed

    Chrast, Roman; Saher, Gesine; Nave, Klaus-Armin; Verheijen, Mark H G

    2011-03-01

    The integrity of central and peripheral nervous system myelin is affected in numerous lipid metabolism disorders. This vulnerability was so far mostly attributed to the extraordinarily high level of lipid synthesis that is required for the formation of myelin, and to the relative autonomy in lipid synthesis of myelinating glial cells because of blood barriers shielding the nervous system from circulating lipids. Recent insights from analysis of inherited lipid disorders, especially those with prevailing lipid depletion and from mouse models with glia-specific disruption of lipid metabolism, shed new light on this issue. The particular lipid composition of myelin, the transport of lipid-associated myelin proteins, and the necessity for timely assembly of the myelin sheath all contribute to the observed vulnerability of myelin to perturbed lipid metabolism. Furthermore, the uptake of external lipids may also play a role in the formation of myelin membranes. In addition to an improved understanding of basic myelin biology, these data provide a foundation for future therapeutic interventions aiming at preserving glial cell integrity in metabolic disorders.

  13. Lipid metabolism in myelinating glial cells: lessons from human inherited disorders and mouse models

    PubMed Central

    Chrast, Roman; Saher, Gesine; Nave, Klaus-Armin; Verheijen, Mark H. G.

    2011-01-01

    The integrity of central and peripheral nervous system myelin is affected in numerous lipid metabolism disorders. This vulnerability was so far mostly attributed to the extraordinarily high level of lipid synthesis that is required for the formation of myelin, and to the relative autonomy in lipid synthesis of myelinating glial cells because of blood barriers shielding the nervous system from circulating lipids. Recent insights from analysis of inherited lipid disorders, especially those with prevailing lipid depletion and from mouse models with glia-specific disruption of lipid metabolism, shed new light on this issue. The particular lipid composition of myelin, the transport of lipid-associated myelin proteins, and the necessity for timely assembly of the myelin sheath all contribute to the observed vulnerability of myelin to perturbed lipid metabolism. Furthermore, the uptake of external lipids may also play a role in the formation of myelin membranes. In addition to an improved understanding of basic myelin biology, these data provide a foundation for future therapeutic interventions aiming at preserving glial cell integrity in metabolic disorders. PMID:21062955

  14. Potential role of liver enzymes levels as predictor markers of glucose metabolism disorders in Tunisian population.

    PubMed

    Bouhajja, Houda; Abdelhedi, Rania; Amouri, Ali; Hadj Kacem, Faten; Marrakchi, Rim; Safi, Wajdi; Mrabet, Houcem; Chtourou, Lassaad; Charfi, Nadia; Fourati, Mouna; Bensassi, Salwa; Jamoussi, Kamel; Abid, Mohamed; Ayadi, Hammadi; Feki, Mouna Mnif; Elleuch, Noura Bougacha

    2018-03-10

    The relationship between liver enzymes and type 2 diabetes (T2D) risk is inconclusive. We aimed to evaluate the association between liver markers and risk of carbohydrate metabolism disorders and their discriminatory power for T2D prediction. This cross-sectional study enrolled 216 participants classified as normoglycemic, prediabetes, newly-diagnosed diabetes and diagnosed diabetes. All participants underwent anthropometric and biochemical measurements. The relationship between hepatic enzymes and glucose metabolism markers was evaluated by ANCOVA analyses. The associations between liver enzymes and incident carbohydrate metabolism disorders were analyzed through logistic regression and their discriminatory capacity for T2D by receiver operating characteristic (ROC) analysis. High alkaline phosphatase (AP), alanine aminotransferase (ALT), γ-glutamyltransferase (γGT) and aspartate aminotrasferase (AST) levels were independently related to decreased insulin sensitivity. Interestingly, higher AP level was significantly associated with increased risk of prediabetes (p=0.017), newly-diagnosed diabetes (p=0.004) and T2D (p=0.007). Elevated γGT level was an independent risk factor for T2D (p=0.032) and undiagnosed-T2D (p=0.010) in prediabetic and normoglycemic subjects, respectively. In ROC analysis, AP was a powerful predictor of incident diabetes and significantly improved T2D prediction. Liver enzymes within normal range, specifically AP levels, are associated with increased risk of carbohydrate metabolism disorders and significantly improved T2D prediction.

  15. Neuroprotective effects of leptin in the context of obesity and metabolic disorders.

    PubMed

    Davis, Cecilia; Mudd, Jeremy; Hawkins, Meredith

    2014-12-01

    As the population of the world ages, the prevalence of neurodegenerative disease continues to rise, accompanied by increases in disease burden related to obesity and metabolic disorders. Thus, it will be essential to develop tools for preventing and slowing the progression of these major disease entities. Epidemiologic studies have shown strong associations between obesity, metabolic dysfunction, and neurodegeneration, while animal models have provided insights into the complex relationships between these conditions. Experimentally, the fat-derived hormone leptin has been shown to act as a neuroprotective agent in various animal models of dementia, toxic insults, ischemia/reperfusion, and other neurodegenerative processes. Specifically, leptin minimizes neuronal damage induced by neurotoxins and pro-apoptotic conditions. Leptin has also demonstrated considerable promise in animal models of obesity and metabolic disorders via modulation of glucose homeostasis and energy intake. However, since obesity is known to induce leptin resistance, we hypothesize that resistance to the neuroprotective effects of leptin contributes to the pathogenesis of obesity-associated neurodegenerative diseases. This review aims to explore the literature pertinent to the role of leptin in the protection of neurons from the toxic effects of aging, obesity and metabolic disorders, to investigate the physiological state of leptin resistance and its causes, and to consider how leptin might be employed therapeutically in the prevention and treatment of neurodegenerative disease. Copyright © 2014 Elsevier Inc. All rights reserved.

  16. Factors influencing insulin resistance in relation to atherogenicity in mood disorders, the metabolic syndrome and tobacco use disorder.

    PubMed

    Bortolasci, Chiara Cristina; Vargas, Heber Odebrecht; Vargas Nunes, Sandra Odebrecht; de Melo, Luiz Gustavo Piccoli; de Castro, Márcia Regina Pizzo; Moreira, Estefania Gastaldello; Dodd, Seetal; Barbosa, Décio Sabbatini; Berk, Michael; Maes, Michael

    2015-07-01

    This study examines the effects of malondialdehyde (MDA) and uric acid on insulin resistance and atherogenicity in subjects with and without mood disorders, the metabolic syndrome (MetS) and tobacco use disorder (TUD). We included 314 subjects with depression and bipolar depression, with and without the MetS and TUD and computed insulin resistance using the updated homeostasis model assessment (HOMA2IR) and atherogenicity using the atherogenic index of plasma (AIP), that is log10 (triglycerides/high density lipoprotein (HDL) cholesterol. HOMA2IR is correlated with body mass index (BMI) and uric acid levels, but not with mood disorders and TUD, while the AIP is positively associated with BMI, mood disorders, TUD, uric acid, MDA and male sex. Uric acid is positively associated with insulin and triglycerides and negatively with HDL cholesterol. MDA is positively associated with triglyceride levels. Comorbid mood disorders and TUD further increase AIP but not insulin resistance. Glucose is positively associated with increasing age, male gender and BMI. The results show that mood disorders, TUD and BMI together with elevated levels of uric acid and MDA independently contribute to increased atherogenic potential, while BMI and uric acid are risk factors for insulin resistance. The findings show that mood disorders and TUD are closely related to an increased atherogenic potential but not to insulin resistance or the MetS. Increased uric acid is a highly significant risk factor for insulin resistance and increased atherogenic potential. MDA, a marker of lipid peroxidation, further contributes to different aspects of the atherogenic potential. Mood disorders and TUD increase triglyceride levels, lower HDL cholesterol and are strongly associated with the atherogenic, but not insulin resistance, component of the MetS. Copyright © 2015 Elsevier B.V. All rights reserved.

  17. Influence of injected caffeine on the metabolism of calcium and the retention and excretion of sodium, potassium, phosphorus, magnesium, zinc and copper in rats.

    PubMed

    Yeh, J K; Aloia, J F; Semla, H M; Chen, S Y

    1986-02-01

    Mineral metabolism was studied by the metabolic balance technique in rats with and without administration of caffeine. Caffeine was injected subcutaneously each day at either 2.5 mg or 10 mg/100 g body weight for 2 wk before the balance studies. Urinary volume excretion was higher in the group given caffeine than in the control group, but the creatinine clearance was not different. Urinary excretion of potassium, sodium, inorganic phosphate, magnesium and calcium, but not of zinc and copper, was also higher in the rats given caffeine. The rank order of the difference was the same as the percent of ingested mineral excreted in urine in the absence of caffeine. Caffeine caused a negative balance of potassium, sodium and inorganic phosphate. There was no significant difference from the control levels and in the apparent metabolic balance of calcium and magnesium. The urinary and fecal excretion of zinc and copper were found to be unaffected by caffeine. It is suggested that chronic administration of caffeine may lead to a tendency toward deficiency of those minerals that are excreted primarily in urine.

  18. [Regulative effects of the acupuncture on glucose and lipid metabolism disorder in the patients of metabolic syndrome].

    PubMed

    Chen, Jie; Xing, Haijiao; Li, Qing; Li, Mei; Wang, Shaojin

    2017-04-12

    To observe the regulative effects of the acupuncture on glucose and lipid metabolism disorder in the patients of metabolic syndrome. Seventy-six patients of metabolic syndrome were rando-mized into an acupuncture plus western medicine group (37 cases) and a western medicine group (39 cases). In the western medicine group, the conventional western medication was used for 40 days. In the acupuncture plus western medicine group, the acupuncture was combined on the basis of the treatment as the western medicine group, the acupoints were Danzhong (CV 17), Zhongwan (CV 12), Tianshu (ST 25), etc. Ten treatments were as one session. There were 3 to 5 days of intervals between the sessions and totally 30 treatments were required. The body mass index (BMI), blood lipid, blood glucose, and comprehensive therapeutic effects were compared before and after treatment in the two groups. Before and after treatment, the differences were all significant in BMI, triglyceride (TG), total cholesterol (TC), low-density lipoprotein cholesterol (LDL-C), high density lipoprotein cholesterol (HDL-C), fasting blood glucose (FBG), plasma glucose of 2 hours post glucose-load (2 hPG), fasting insulin (FINS) and insulin resistance index (HOMA-IR) (all P <0.05) in the acupuncture plus western medicine group, and the results after treatment were superior to those before treatment; the difference was not significant in BMI ( P >0.05) and those were all significant statistically in TG, TC, LDL-C, HDL-C, FBG, 2 hPG, FINS, HOMA-IR (all P <0.05) in the western medicine group, and the results after treatment were superior to those before treatment. After treatment, in comparison of the two groups, the results in the acupuncture plus western medicine group were better than those in the western medicine group. The differences were all signif-icant sta-tistically in BMI, TG, TC, LDL-C, HDL-C, FBG, 2 hPG, FINS, HOMA-IR (all P <0.05). On the basis of the conventional western medicine, the acupuncture relieves

  19. Association Between Vitamin D Insufficiency and Metabolic Syndrome in Patients With Psychotic Disorders

    PubMed Central

    Yoo, Taeyoung; Choi, Wonsuk; Hong, Jin-Hee; Lee, Ju-Yeon; Kim, Jae-Min; Shin, Il-Seon; Yang, Soo Jin; Amminger, Paul; Berk, Michael; Yoon, Jin-Sang; Kim, Sung-Wan

    2018-01-01

    Objective This study examined the association between vitamin D and metabolic syndrome in patients with psychotic disorders. Methods The study enrolled 302 community-dwelling patients with psychotic disorders. Sociodemographic and clinical characteristics, including blood pressure, physical activity, and dietary habit were gathered. Laboratory examinations included vitamin D, lipid profile, fasting plasma glucose, HbA1c, liver function, and renal function. Vitamin D insufficiency was defined as <20 ng/mL. Clinical characteristics associated with vitamin D insufficiency were identified. Results Among the 302 participants, 236 patients (78.1%) had a vitamin D insufficiency and 97 (32.1%) had metabolic syndrome. Vitamin D insufficiency was significantly associated with the presence of metabolic syndrome (p=0.006) and hypertension (p=0.017). Significant increases in triglycerides and alanine transaminase were observed in the group with a vitamin D insufficiency (p=0.002 and 0.011, respectively). After adjusting for physical activity and dietary habit scores, vitamin D insufficiency remained significantly associated with metabolic syndrome and hypertension. Conclusion Vitamin D insufficiency was associated with metabolic syndrome and was particularly associated with high blood pressure, although the nature, direction and implications of this association are unclear. PMID:29486549

  20. Association Between Vitamin D Insufficiency and Metabolic Syndrome in Patients With Psychotic Disorders.

    PubMed

    Yoo, Taeyoung; Choi, Wonsuk; Hong, Jin-Hee; Lee, Ju-Yeon; Kim, Jae-Min; Shin, Il-Seon; Yang, Soo Jin; Amminger, Paul; Berk, Michael; Yoon, Jin-Sang; Kim, Sung-Wan

    2018-04-01

    This study examined the association between vitamin D and metabolic syndrome in patients with psychotic disorders. The study enrolled 302 community-dwelling patients with psychotic disorders. Sociodemographic and clinical characteristics, including blood pressure, physical activity, and dietary habit were gathered. Laboratory examinations included vitamin D, lipid profile, fasting plasma glucose, HbA1c, liver function, and renal function. Vitamin D insufficiency was defined as <20 ng/mL. Clinical characteristics associated with vitamin D insufficiency were identified. Among the 302 participants, 236 patients (78.1%) had a vitamin D insufficiency and 97 (32.1%) had metabolic syndrome. Vitamin D insufficiency was significantly associated with the presence of metabolic syndrome (p=0.006) and hypertension (p=0.017). Significant increases in triglycerides and alanine transaminase were observed in the group with a vitamin D insufficiency (p=0.002 and 0.011, respectively). After adjusting for physical activity and dietary habit scores, vitamin D insufficiency remained significantly associated with metabolic syndrome and hypertension. Vitamin D insufficiency was associated with metabolic syndrome and was particularly associated with high blood pressure, although the nature, direction and implications of this association are unclear.

  1. Impact of Calcium and Two Doses of Vitamin D on Bone Metabolism in the Elderly: A Randomized Controlled Trial.

    PubMed

    Rahme, Maya; Sharara, Sima Lynn; Baddoura, Rafic; Habib, Robert H; Halaby, Georges; Arabi, Asma; Singh, Ravinder J; Kassem, Moustapha; Mahfoud, Ziyad; Hoteit, Maha; Daher, Rose T; Bassil, Darina; El Ferkh, Karim; El-Hajj Fuleihan, Ghada

    2017-07-01

    The optimal dose of vitamin D to optimize bone metabolism in the elderly is unclear. We tested the hypothesis that vitamin D, at a dose higher than recommended by the Institute of Medicine (IOM), has a beneficial effect on bone remodeling and mass. In this double-blind trial we randomized 257 overweight elderly subjects to receive 1000 mg of elemental calcium citrate/day, and the daily equivalent of 3750 IU/day or 600 IU/day of vitamin D3 for 1 year. The subjects' mean age was 71 ± 4 years, body mass index 30 ± 4 kg/m 2 , 55% were women, and 222 completed the 12-month follow-up. Mean serum 25 hydroxyvitamin D (25OHD) was 20 ng/mL, and rose to 26 ng/mL in the low-dose arm, and 36 ng/mL in the high-dose arm, at 1 year (p < 0.05). Plasma parathyroid hormone, osteocalcin, and C-terminal telopeptide (Cross Laps) levels decreased significantly by 20% to 22% in both arms, but there were no differences between the two groups for any variable, at 6 or 12 months, with the exception of serum calcitriol, which was higher in the high-dose group at 12 months. Bone mineral density (BMD) increased significantly at the total hip and lumbar spine, but not the femoral neck, in both study arms, whereas subtotal body BMD increased in the high-dose group only, at 1 year. However, there were no significant differences in percent change BMD between the two study arms at any skeletal site. Subjects with serum 25OHD <20 ng/mL and PTH level >76 pg/mL showed a trend for higher BMD increments at all skeletal sites, in the high-dose group, that reached significance at the hip. Adverse events were comparable in the two study arms. This controlled trial shows little additional benefit in vitamin D supplementation at a dose exceeding the IOM recommendation of 600 IU/day on BMD and bone markers, in overweight elderly individuals. © 2017 American Society for Bone and Mineral Research. © 2017 American Society for Bone and Mineral Research.

  2. Application of research findings and summary of research needs: Bud Britton Memorial Symposium on Metabolic Disorders of Feedlot Cattle.

    PubMed

    Galyean, M L; Eng, K S

    1998-01-01

    Updated research findings with acidosis, feedlot bloat, liver abscesses, and sudden death syndromes were presented at the Bud Britton Memorial Symposium on Metabolic Disorders of Feedlot Cattle. Possible industry applications include the need to establish guidelines for use of clostridial vaccines in feedlot cattle, further assessment of the relationship between acidosis and polioencephalomalacia, examination of the effects of various ionophores on the incidence of metabolic disorders, and evaluation of the effects of feed bunk management and limit- and restricted-feeding programs on the incidence of metabolic disorders. A multidisciplinary approach among researchers, consulting nutritionists and veterinarians, and feedlot managers will be required for effective progress in research and in the application of research findings. Areas suggested for further research include 1) assessment of feed consumption patterns and social behavior of cattle in large-pen, feedlot settings; 2) evaluation of the relationship between feed intake management systems (feed bunk management programs, limit- and programmed-feeding) and the incidence of metabolic disorders, including delineation of the role of variability in feed intake in the etiology of such disorders; 3) efforts to improve antemortem and postmortem diagnosis, and to establish standardized regional or national epidemiological databases for various metabolic disorders; 4) ascertaining the accuracy of diagnosis of metabolic disorders and determining the relationship of previous health history of animals to the incidence of metabolic disorders; 5) further defining ruminal and intestinal microbiology as it relates to metabolic disorders and deeper evaluation of metabolic changes that occur with such disorders; 6) continued appraisal of the effects of grain processing and specific feed ingredients and nutrients on metabolic disorders, and development of new feed additives to control or prevent these disorders; and 7

  3. Analysis of gene expression and regulation implicates C2H9orf152 has an important role in calcium metabolism and chicken reproduction.

    PubMed

    Liu, Long; Fan, Yanfeng; Zhang, Zhenhe; Yang, Chan; Geng, Tuoyu; Gong, Daoqing; Hou, Zhuocheng; Ning, Zhonghua

    2017-01-01

    The reproductive system of a female bird is responsible for egg production. The genes highly expressed in oviduct are potentially important. From RNA-seq analysis, C2H9orf152 (an orthologous gene of human C9orf152) was identified as highly expressed in chicken uterus. To infer its function, we obtained and characterized its complete cDNA sequence, determined its spatiotemporal expression, and probed its transcription factor(s) through pharmaceutical approach. Data showed that the complete cDNA sequence was 1468bp long with a 789bp of open reading frame. Compared to other tested tissues, this gene was highly expressed in the oviduct and liver tissues, especially uterus. Its expression in uterus was gradually increased during developmental and reproductive periods, which verified its involvement in the growth and maturity of reproductive system. In contrast, its expression was not significant different between active and quiescent uterus, suggesting the role of C2H9orf152 in reproduction is likely due to its long-term effect. Moreover, based on its 5'-flanking sequence, Foxd3 and Hnf4a were predicted as transcription factors of C2H9orf152. Using berberine or retinoic acid (which can regulate the activities of Hnf4a and Foxd3, respectively), we demonstrated suppression of C2H9orf152 by the chemicals in chicken primary hepatocytes. As retinoic acid regulates calcium metabolism, and Hnf4a is a key nuclear factor to liver, these findings suggest that C2H9orf152 is involved in liver function and calcium metabolism of reproductive system. In conclusion, C2H9orf152 may have a long-term effect on chicken reproductive system by regulating calcium metabolism, suggesting this gene has an important implication in the improvement of egg production and eggshell quality. Copyright © 2016 Elsevier B.V. All rights reserved.

  4. A Marker of Endotoxemia Is Associated With Obesity and Related Metabolic Disorders in Apparently Healthy Chinese

    PubMed Central

    Sun, Liang; Yu, Zhijie; Ye, Xingwang; Zou, Shurong; Li, Huaixing; Yu, Danxia; Wu, Hongyu; Chen, Yan; Dore, Joel; Clément, Karine; Hu, Frank B.; Lin, Xu

    2010-01-01

    OBJECTIVE Elevated lipopolysaccharide-binding protein (LBP), a marker of subclinical endotoxemia, may be involved in the pathogenesis of obesity and metabolic risk. We aimed to investigate the association between plasma LBP and metabolic disorders in apparently healthy Chinese. RESEARCH DESIGN AND METHODS A population-based study including 559 overweight/obese (BMI ≥24.0 kg/m2) and 500 normal-weight (18.0 ≤ BMI <24.0 kg/m2) subjects aged 35–54 years was conducted in Shanghai, China. Fasting plasma glucose, lipid profile, LBP, high-sensitivity C-reactive protein, interleukin-6, high-molecular-weight (HMW) adiponectin, leptin, hepatic enzymes, and body composition were measured. Metabolic syndrome was defined by the updated National Cholesterol Education Program Adult Treatment Panel III criterion for Asian Americans. RESULTS LBP levels were significantly higher in overweight/obese individuals than in normal-weight individuals (geometric mean 27.6 [95% CI 25.2–30.3] vs. 10.0 [9.1–11.1] μg/ml; P < 0.001). After multiple adjustments including BMI, the odds ratios were 3.54 (95% CI 2.05–6.09) and 5.53 (95% CI 2.64–11.59) for metabolic syndrome and type 2 diabetes, respectively, comparing the highest with the lowest LBP quartile. Further adjustments for inflammatory markers almost abolished the significant association of LBP with metabolic syndrome but not that with type 2 diabetes, and controlling for adipokines and hepatic enzymes did not substantially alter the results. CONCLUSIONS Elevated circulating LBP was associated with obesity, metabolic syndrome, and type 2 diabetes in apparently healthy Chinese. These findings suggested a role of lipopolysaccharide via initiation of innate immune mechanism(s) in metabolic disorders. Prospective studies are needed to confirm these results. PMID:20530747

  5. Metabolic syndrome among individuals with heroin use disorders on methadone therapy: Prevalence, characteristics, and related factors.

    PubMed

    Vallecillo, Gabriel; Robles, María José; Torrens, Marta; Samos, Pilar; Roquer, Albert; Martires, Paula K; Sanvisens, Arantza; Muga, Roberto; Pedro-Botet, Juan

    2018-01-02

    Observational studies have reported a high prevalence of obesity and diabetes in subjects on methadone therapy; there are, however, limited data about metabolic syndrome. The aim of the study was to evaluate the prevalence of metabolic syndrome and related factors in individuals with heroin use disorder on methadone therapy. A cross-sectional study in individuals with heroin use disorder on methadone therapy at a drug abuse outpatient center. Medical examinations and laboratory analyses after a 12-hour overnight fast were recorded. Metabolic syndrome was diagnosed according to the National Cholesterol Education Program Adult Treatment Panel III (ATP III) criteria. One hundred and twenty-two subjects were included, with a mean age of 46.1 ± 9 years, a median body mass index (BMI) of 25.3 kg/m 2 (interquartile range [IQR]: 21.2-28), and 77.9% were men. Median exposure to methadone therapy was 13 years (IQR: 5-20). Overweight and obesity were present in 29.5% and 17.2% of the participants, respectively. Metabolic syndrome components were low high-density lipoprotein (HDL) cholesterol (51.6%), hypertriglyceridemia (36.8%), high blood pressure (36.8%), abdominal obesity (27.0%), and raised blood glucose levels (18.0%). Abdominal obesity was more prevalent in women (52% vs. 20%, P = >0.01) and high blood pressure more prevalent in men (41.1% vs. 22.2%, P = .07). Prevalence of metabolic syndrome was 29.5% (95% confidence interval [CI]: 16.6-31.8). In the multivariate logistic regression analysis, BMI (per 1 kg/m 2 increase odds ratio [OR]: 1.49, 95% CI: 1.27-1.76) and exposure time to methadone therapy (per 5 years of treatment increase OR: 1.38, 95% CI: 1.28-1.48) were associated with metabolic syndrome. Overweight and metabolic syndrome are prevalent findings in individuals with heroin use disorder on methadone therapy. Of specific concern is the association of methadone exposure with metabolic syndrome. Preventive measures and clinical routine screening should be

  6. Metabolic syndrome in subjects with bipolar disorder and major depressive disorder in a current depressive episode: Population-based study: Metabolic syndrome in current depressive episode.

    PubMed

    Moreira, Fernanda Pedrotti; Jansen, Karen; Cardoso, Taiane de Azevedo; Mondin, Thaíse Campos; Magalhães, Pedro Vieira da Silva; Kapczinski, Flávio; Souza, Luciano Dias de Mattos; da Silva, Ricardo Azevedo; Oses, Jean Pierre; Wiener, Carolina David

    2017-09-01

    To assess the differences in the prevalence of the metabolic syndrome (MetS) and their components in young adults with bipolar disorder (BD) and major depressive disorder (MDD) in a current depressive episode. This was a cross-sectional study with young adults aged 24-30 years old. Depressive episode (bipolar or unipolar) was assessed using the Mini International Neuropsychiatric Interview - Plus version (MINI Plus). The MetS was assessed using the National Cholesterol Education Program Adult Treatment Panel III (NCEP/ATP III). The sample included 972 subjects with a mean age of 25.81 (±2.17) years. Both BD and MDD patients showed higher prevalence of MetS compared to the population sample (BD = 46.9%, MDD = 35.1%, population = 22.1%, p < 0.001). Higher levels of glucose, total cholesterol and LDL cholesterol, Body Mass Index, low levels of HDL cholesterol, and a higher prevalence of abdominal obesity were observed in both BD and MDD individuals with current depressive episode compared to the general population. Moreover, there was a significant difference on BMI values in the case of BD and MDD subjects (p = 0.016). Metabolic components were significantly associated with the presence of depressive symptoms, independently of the diagnosis. Copyright © 2017. Published by Elsevier Ltd.

  7. High-fat diet induces significant metabolic disorders in a mouse model of polycystic ovary syndrome.

    PubMed

    Lai, Hao; Jia, Xiao; Yu, Qiuxiao; Zhang, Chenglu; Qiao, Jie; Guan, Youfei; Kang, Jihong

    2014-11-01

    Polycystic ovary syndrome (PCOS) is the most common female endocrinopathy associated with both reproductive and metabolic disorders. Dehydroepiandrosterone (DHEA) is currently used to induce a PCOS mouse model. High-fat diet (HFD) has been shown to cause obesity and infertility in female mice. The possible effect of an HFD on the phenotype of DHEA-induced PCOS mice is unknown. The aim of the present study was to investigate both reproductive and metabolic features of DHEA-induced PCOS mice fed a normal chow or a 60% HFD. Prepubertal C57BL/6 mice (age 25 days) on the normal chow or an HFD were injected (s.c.) daily with the vehicle sesame oil or DHEA for 20 consecutive days. At the end of the experiment, both reproductive and metabolic characteristics were assessed. Our data show that an HFD did not affect the reproductive phenotype of DHEA-treated mice. The treatment of HFD, however, caused significant metabolic alterations in DHEA-treated mice, including obesity, glucose intolerance, dyslipidemia, and pronounced liver steatosis. These findings suggest that HFD induces distinct metabolic features in DHEA-induced PCOS mice. The combined DHEA and HFD treatment may thus serve as a means of studying the mechanisms involved in metabolic derangements of this syndrome, particularly in the high prevalence of hepatic steatosis in women with PCOS. © 2014 by the Society for the Study of Reproduction, Inc.

  8. Circulating PCSK9 in patients with type 2 diabetes and related metabolic disorders.

    PubMed

    Ibarretxe, Daiana; Girona, Josefa; Plana, Núria; Cabré, Anna; Ferré, Raimón; Amigó, Núria; Guaita, Sandra; Mallol, Roger; Heras, Mercedes; Masana, Luis

    2016-01-01

    PCSK9 is a pivotal molecule in the regulation of lipid metabolism. Previous studies have suggested that PCSK9 expression and its function in LDL receptor regulation could be altered in the context of diabetes. The aim was to assess PCSK9 plasma levels in patients with type 2 diabetes (T2DM) and other related metabolic disorders as well as its relation to the metabolomic profile generated by nuclear magnetic resonance (NMR) and glucose homeostasis. There were recruited a total of 457 patients suffering from T2DM and other metabolic disorders (metabolic syndrome (MetS), obesity and atherogenic dyslipidaemia (AD) and other disorders). Anamnesis, anthropometry and physical examinations were conducted, and vascular and abdominal adiposity imaging were carried out. Biochemical studies were performed to determine PCSK9 plasma levels 6 weeks after lipid lowering drug wash-out in treated patients. A complete metabolomic lipid profile was also generated by NMR. The rs505151 and rs11591147 genetic variants of PCSK9 gene were identified in patients. The results showed that PCSK9 levels are increased in patients with T2DM and MetS (14% and 13%; p<0.005, respectively). Circulating PCSK9 levels were correlated with an atherogenic lipid profile and with insulin resistance parameters. PCSK9 levels were also positively associated with AD, as defined by lipoprotein particle number and size. The rs11591147 genetic variant resulted in lower levels of circulating PCSK9 and LDL cholesterol (LDL-C). PCSK9 plasma levels are increased in T2DM and MetS patients and are associated with LDL-C and other parameters of AD and glucose metabolism. Copyright © 2015 Sociedad Española de Arteriosclerosis. Published by Elsevier España. All rights reserved.

  9. Association between the abdominal obesity anthropometric indicators and metabolic disorders in a Chinese population.

    PubMed

    Dong, J; Ni, Y-Q; Chu, X; Liu, Y-Q; Liu, G-X; Zhao, J; Yang, Y-B; Yan, Y-X

    2016-02-01

    Obesity has become a major health problem in contemporary society and it is closely related to many chronic diseases, so it is an important issue for measuring adiposity accurately and predicting its future. Prevention and treatment of overweight and obesity has become one of the key prevention and treatment of metabolic disorders. In this study, we compared the ability of the four anthropometric indicators (body mass index, waist circumstance, waist-height ratio, waist-to-hip ratio) to identify metabolic disorders (hypertension, hyperlipidaemia, hyperglycemia and hyperuricemia) by receiver operating characteristic (ROC) curve analyses and to provide evidence for clinical practice. In this large scale cross-sectional study, 13,275 Han adults (including 7595 males and 5680 females) received physical examination between January, 2009 and January, 2010 in Xuanwu Hospital of Capital Medical University were investigated by the means of questionnaire, Meanwhile, the physical examination and serological results were recorded. A package known as Statistical Package for Social Scientist (SPSS) was employed to analyse the responses while t-test, one-way analysis of variance (ANOVA), ROC analysis and chi-square statistical methods were used to test the hypotheses. WC, WHtR, WHR and BMI were all significantly (P < 0.001) correlated with all metabolic risk factors regardless of gender. And the area under the curve (AUC) of WHtR was significantly greater than that of WC, BMI or WHR in the prediction of hypertension, hyperlipidaemia, hyperglycemia and hyperuricemia. Our data show that WHtR was the best predictor of various metabolic disorders. The diagnostic value in descending order was WHtR > WHR > WC > BMI. Therefore we recommend WHtR in assessment of obese patients, in order to better assess the risks of their metabolic diseases. Copyright © 2015 The Royal Society for Public Health. Published by Elsevier Ltd. All rights reserved.

  10. Posttraumatic Stress Disorder and Metabolic Syndrome: Retrospective Study of Repatriated Prisoners of War

    DTIC Science & Technology

    2011-04-01

    density lipoprotein (HDL) cholesterol (HDL-C), elevated triglycerides (TGs), and impaired fasting glucose or impaired glucose tolerance. 3 MbS is a...Stress Disorder and Metabolic Syndrome MILITARY MEDICINE, Vol. 176, April 2011 373 targeted at elevated low- density lipoprotein cholesterol , which is... relationship between PTSD and MbS. ACKNOWLEDGMENTS We thank the staff of the Robert E. Mitchell Center for Prisoner of War Studies for the high

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

    PubMed

    Vancampfort, Davy; Stubbs, Brendon

    2017-12-15

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

  12. Genetic and pharmacological correction of aberrant dopamine synthesis using patient iPSCs with BH4 metabolism disorders.

    PubMed

    Ishikawa, Taizo; Imamura, Keiko; Kondo, Takayuki; Koshiba, Yasushi; Hara, Satoshi; Ichinose, Hiroshi; Furujo, Mahoko; Kinoshita, Masako; Oeda, Tomoko; Takahashi, Jun; Takahashi, Ryosuke; Inoue, Haruhisa

    2016-12-01

    Dopamine (DA) is a neurotransmitter in the brain, playing a central role in several disease conditions, including tetrahydrobiopterin (BH4) metabolism disorders and Parkinson's disease (PD). BH4 metabolism disorders present a variety of clinical manifestations including motor disturbance via altered DA metabolism, since BH4 is a cofactor for tyrosine hydroxylase (TH), a rate-limiting enzyme for DA synthesis. Genetically, BH4 metabolism disorders are, in an autosomal recessive pattern, caused by a variant in genes encoding enzymes for BH4 synthesis or recycling, including 6-pyruvoyltetrahydropterin synthase (PTPS) or dihydropteridine reductase (DHPR), respectively. Although BH4 metabolism disorders and its metabolisms have been studied, it is unclear how gene variants cause aberrant DA synthesis in patient neurons. Here, we generated induced pluripotent stem cells (iPSCs) from BH4 metabolism disorder patients with PTPS or DHPR variants, corrected the gene variant in the iPSCs using the CRISPR/Cas9 system, and differentiated the BH4 metabolism disorder patient- and isogenic control iPSCs into midbrain DA neurons. We found that by the gene correction, the BH4 amount, TH protein level and extracellular DA level were restored in DA neuronal culture using PTPS deficiency iPSCs. Furthermore, the pharmacological correction by BH4 precursor sepiapterin treatment also improved the phenotypes of PTPS deficiency. These results suggest that patient iPSCs with BH4 metabolism disorders provide an opportunity for screening substances for treating aberrant DA synthesis-related disorders. © The Author 2016. Published by Oxford University Press.

  13. A study of changes in bone metabolism in cases of gender identity disorder.

    PubMed

    Miyajima, Tsuyoshi; Kim, Yoon Taek; Oda, Hiromi

    2012-07-01

    The aim of this study was to determine the effect of increasing estrogen and decreasing androgen in males and increasing androgen and decreasing estrogen in females on bone metabolism in patients with gender identity disorder (GID). We measured and examined bone mineral density (BMD) and bone metabolism markers retrospectively in GID patients who were treated in our hospital. In addition, we studied the effects of treatment on those who had osteoporosis. Patients who underwent a change from male to female (MtF) showed inhibition of bone resorption and increased L2-4 BMD whereas those who underwent a change from female to male (FtM) had increased bone resorption and decreased L2-4 BMD. Six months after administration of risedronate to FtM patients with osteoporosis, L2-4 BMD increased and bone resorption markers decreased. These results indicate that estrogen is an important element with regard to bone metabolism in males.

  14. Should waist circumference be used to identify metabolic disorders than BMI in South Korea?

    PubMed

    Lee, S-K

    2010-11-01

    Although indicators of central obesity have been suggested as a better alternative to body mass index (BMI), yet mixed results exist. This study examined whether waist circumference (WC) was better in identifying metabolic disorders than BMI at two time points. This study used nationally representative 1998 and 2005 Korea National Health and Nutrition Examination Survey data sets. Odds ratios from logistic regressions and area under the curves (AUC) were calculated. BMI and WC showed similar level of odds ratios (1.1-1.6) to diabetes, hypertension, dyslipidemia and having two or three metabolic syndrome criteria. The AUC comparison, however, indicated that, in only women, WC was a better discriminator for diabetes, hypertension and having two or three metabolic syndrome criteria. No meaningful differences were found between 1998 and 2005. Prospective studies to weigh practical and clinical relevance are needed to assert the use of WC over BMI in clinical and public health settings.

  15. [Role of calcium ions in the mechanism of action of acetylcholine on energy metabolism in rat liver mitochondria].

    PubMed

    Vatamaniuk, M Z; Artym, V V; Kuka, O B; Doliba, M M; Shostakovs'ka, I V

    1996-01-01

    It is shown that administration of acetylcholine to animals (50 micrograms per 100 g of body weight) leads to the activation of respiration and oxidative phosphorylation in the rat liver mitochondria under oxidation of alpha-ketoglutarate; this effect depends on the concentration of calcium ions in the incubation medium of mitochondria. The rate of ADP-stimulated respiration of mitochondria of experimental animals reaches its maximum level under lower concentrations of Ca2+ than in the control animals. The results of investigation of dependence of acetyl choline effect on respiration of mitochondria on the concentration of alpha-ketoglutarate in calcium and calcium-free incubation medium have shown that the half-maximum effect of acetylcholine is observed in calcium medium at lower concentration of the substrate than in calcium-free medium. The latter indicates to the increase of affinity of alpha-ketoglutarate dehydrogenase to alpha-ketoglutarate under these conditions. It is found out that acetylcholine (1.10(-8) M) increases the rate of ADP- and Ca(2+)-stimulated respiration of mitochondria of isolated perfused rat liver, while mutual effect of verapamyl and niphedipin removes this effect.

  16. Computational modeling to predict nitrogen balance during acute metabolic decompensation in patients with urea cycle disorders

    PubMed Central

    MacLeod, Erin L.; Hall, Kevin D.; McGuire, Peter J.

    2015-01-01

    SUMMARY Nutritional management of acute metabolic decompensation in amino acid inborn errors of metabolism (AA IEM) aims to restore nitrogen balance. While nutritional recommendations have been published, they have never been rigorously evaluated. Furthermore, despite these recommendations, there is a wide variation in the nutritional strategies employed amongst providers, particularly regarding the inclusion of parenteral lipids for protein-free caloric support. Since randomized clinical trials during acute metabolic decompensation are difficult and potentially dangerous, mathematical modeling of metabolism can serve as a surrogate for the preclinical evaluation of nutritional interventions aimed at restoring nitrogen balance during acute decompensation in AA IEM. A validated computational model of human macronutrient metabolism was adapted to predict nitrogen balance in response to various nutritional interventions in a simulated patient with a urea cycle disorder (UCD) during acute metabolic decompensation due to dietary non-adherence or infection. The nutritional interventions were constructed from published recommendations as well as clinical anecdotes. Overall, dextrose alone (DEX) was predicted to be better at restoring nitrogen balance and limiting nitrogen excretion during dietary non-adherence and infection scenarios, suggesting that the published recommended nutritional strategy involving dextrose and parenteral lipids (ISO) may be suboptimal. The implications for patients with AA IEM are that the medical course during acute metabolic decompensation may be influenced by the choice of protein-free caloric support. These results are also applicable to intensive care patients undergoing catabolism (postoperative phase or sepsis), where parenteral nutritional support aimed at restoring nitrogen balance may be more tailored regarding metabolic fuel selection. PMID:26260782

  17. Computational modeling to predict nitrogen balance during acute metabolic decompensation in patients with urea cycle disorders.

    PubMed

    MacLeod, Erin L; Hall, Kevin D; McGuire, Peter J

    2016-01-01

    Nutritional management of acute metabolic decompensation in amino acid inborn errors of metabolism (AA IEM) aims to restore nitrogen balance. While nutritional recommendations have been published, they have never been rigorously evaluated. Furthermore, despite these recommendations, there is a wide variation in the nutritional strategies employed amongst providers, particularly regarding the inclusion of parenteral lipids for protein-free caloric support. Since randomized clinical trials during acute metabolic decompensation are difficult and potentially dangerous, mathematical modeling of metabolism can serve as a surrogate for the preclinical evaluation of nutritional interventions aimed at restoring nitrogen balance during acute decompensation in AA IEM. A validated computational model of human macronutrient metabolism was adapted to predict nitrogen balance in response to various nutritional interventions in a simulated patient with a urea cycle disorder (UCD) during acute metabolic decompensation due to dietary non-adherence or infection. The nutritional interventions were constructed from published recommendations as well as clinical anecdotes. Overall, dextrose alone (DEX) was predicted to be better at restoring nitrogen balance and limiting nitrogen excretion during dietary non-adherence and infection scenarios, suggesting that the published recommended nutritional strategy involving dextrose and parenteral lipids (ISO) may be suboptimal. The implications for patients with AA IEM are that the medical course during acute metabolic decompensation may be influenced by the choice of protein-free caloric support. These results are also applicable to intensive care patients undergoing catabolism (postoperative phase or sepsis), where parenteral nutritional support aimed at restoring nitrogen balance may be more tailored regarding metabolic fuel selection.

  18. Metabolic decoupling in daily life in patients with panic disorder and agoraphobia.

    PubMed

    Pfaltz, Monique C; Kolodyazhniy, Vitaliy; Blechert, Jens; Margraf, Jürgen; Grossman, Paul; Wilhelm, Frank H

    2015-09-01

    Various studies have assessed autonomic and respiratory underpinnings of panic attacks, yet the psychophysiological functioning of panic disorder (PD) patients has rarely been examined under naturalistic conditions at times when acute attacks were not reported. We hypothesized that emotional activation in daily life causes physiologically demonstrable deviations from efficient metabolic regulation in PD patients. Metabolic coupling was estimated as within-individual correlations between heart rate (HR) and indices of metabolic activity, i.e., physical activity (measured by 3-axial accelerometry, Acc), and minute ventilation (Vm, measured by calibrated inductive plethysmography, as proxy for oxygen consumption). A total of 565 daytime hours were recorded in 19 PD patients and 20 healthy controls (HC). Pairwise cross-correlations of minute-by-minute averages of these metabolic indices were calculated for each participant and then correlated with several indices of self-reported anxiety. Ambulatory HR was elevated in PD (p = .05, d = 0.67). Patients showed reduced HR-Acc (p < .006, d = 0.97) and HR-Vm coupling (p < .009, d = 0.91). Combining Vm and Acc to predict HR showed the strongest group separation (p < .002, d = 1.07). Discriminant analyses, based on the combination of Vm and Acc to predict HR, classified 77% of all participants correctly. In PD, HR-Acc coupling was inversely related to trait anxiety sensitivity, as well as tonic and phasic daytime anxiety. The novel method that was used demonstrates that anxiety in PD may reduce efficient long-term metabolic coupling. Metabolic decoupling may serve as physiological characteristic of PD and might aid diagnostics for PD and other anxiety disorders. This measure deserves further study in research on health consequences of anxiety and psychosocial stress. Copyright © 2015 Elsevier Ltd. All rights reserved.

  19. Quantitative Proteomic Analysis Reveals Metabolic Alterations, Calcium Dysregulation, and Increased Expression of Extracellular Matrix Proteins in Laminin α2 Chain–deficient Muscle*

    PubMed Central

    de Oliveira, Bruno Menezes; Matsumura, Cintia Y.; Fontes-Oliveira, Cibely C.; Gawlik, Kinga I.; Acosta, Helena; Wernhoff, Patrik; Durbeej, Madeleine

    2014-01-01

    Congenital muscular dystrophy with laminin α2 chain deficiency (MDC1A) is one of the most severe forms of muscular disease and is characterized by severe muscle weakness and delayed motor milestones. The genetic basis of MDC1A is well known, yet the secondary mechanisms ultimately leading to muscle degeneration and subsequent connective tissue infiltration are not fully understood. In order to obtain new insights into the molecular mechanisms underlying MDC1A, we performed a comparative proteomic analysis of affected muscles (diaphragm and gastrocnemius) from laminin α2 chain–deficient dy3K/dy3K mice, using multidimensional protein identification technology combined with tandem mass tags. Out of the approximately 700 identified proteins, 113 and 101 proteins, respectively, were differentially expressed in the diseased gastrocnemius and diaphragm muscles compared with normal muscles. A large portion of these proteins are involved in different metabolic processes, bind calcium, or are expressed in the extracellular matrix. Our findings suggest that metabolic alterations and calcium dysregulation could be novel mechanisms that underlie MDC1A and might be targets that should be explored for therapy. Also, detailed knowledge of the composition of fibrotic tissue, rich in extracellular matrix proteins, in laminin α2 chain–deficient muscle might help in the design of future anti-fibrotic treatments. All MS data have been deposited in the ProteomeXchange with identifier PXD000978 (http://proteomecentral.proteomexchange.org/dataset/PXD000978). PMID:24994560

  20. Associations of circulating calcium and 25-hydroxyvitamin D with glucose metabolism in pregnancy: a cross-sectional study in European and South Asian women.

    PubMed

    Whitelaw, Donald C; Scally, Andrew J; Tuffnell, Derek J; Davies, T Jeffrey; Fraser, William D; Bhopal, Raj S; Wright, John; Lawlor, Debbie A

    2014-03-01

    Vitamin D deficiency is thought to impair insulin action and glucose metabolism; however, previous studies have not examined ethnic differences or the influence of calcium and parathyroid hormone. We investigated this in a cohort of predominantly white European and south Asian women during pregnancy. In this cross-sectional study from an urban population in northern England (53.8°N), 1467 women were recruited when undergoing glucose tolerance testing (75 g oral glucose tolerance test) at 26 weeks' gestation. Gestational diabetes mellitus (GDM) was diagnosed in 137 women (9.3%). Median 25-hydroxyvitamin D concentration for the study population was 9.3 ng/mL (interquartile range 5.2, 16.9) and was higher in European [15.2 ng/mL (10.7, 23.5)] than in south Asian women [5.9 ng/mL (3.9, 9.4), P < .001]. After appropriate adjustment for confounders, 25-hydroxyvitamin D showed a weak inverse association with fasting plasma glucose (FPG; mean difference 1.0% per 1 SD; the ratio of geometric means (RGM) 0.99, 95% confidence interval (CI) 0.98, 1.00), and PTH was weakly associated with FPG (RGM 1.01, 95% CI 1.00, 1.02), but neither was associated with fasting insulin, postchallenge glucose, or GDM. Serum calcium (albumin adjusted) was strongly associated with fasting insulin (RGM 1.06; 95% CI 1.03, 1.08), postchallenge glucose (RGM 1.03, 95% CI 1.01, 1.04), and GDM (odds ratio 1.33, 95% CI 1.06, 1.66) but not with FPG. Associations were similar in European and south Asian women. These findings do not indicate any important association between vitamin D status and glucose tolerance in pregnancy. Relationships between circulating calcium and glucose metabolism warrant further investigation.

  1. Depression, anxiety disorders, and metabolic syndrome in a population at risk for type 2 diabetes mellitus.

    PubMed

    Kahl, Kai G; Schweiger, Ulrich; Correll, Christoph; Müller, Conrad; Busch, Marie-Luise; Bauer, Michael; Schwarz, Peter

    2015-03-01

    Depressive symptoms have been associated with type 2 diabetes mellitus (T2DM), but less is known about anxiety disorders that can be comorbid or exist without depression. We evaluated the prevalence of psychiatric disorders in subjects consecutively examined at an outpatient clinic for diabetes prevention who were at-risk for T2DM, defined by FINDRISK scores, and compared metabolic syndrome (MetS) frequencies between subjects with and without psychiatric morbidity, entering also relevant variables for MetS into multivariate analyses. All subjects underwent an oral glucose tolerance test (OGTT). Psychiatric diagnosis was confirmed using a Structured Clinical Interview for DSM-IV. Of 260 consecutively screened subjects, 150 (56.9±8.1 years old, males=56.7%, BMI=27.2±4.1 kg/m2) were at-risk for T2DM and were included. MetS, present in 27% of males and 25% of females, was significantly associated with having a current anxiety disorder (P<0.001) and lifetime major depression (P<0.001). In logistic regression analysis, MetS was significantly associated with lifetime major depression, presence of any anxiety disorder, body weight, and physical activity. Our data in a high-risk group for T2DM support the association between depressive disorders and MetS, pointing to a similar role of anxiety disorders. Screening for anxiety and depression is recommended in this group at risk for T2DM.

  2. Emerging Role of Corticosteroid-Binding Globulin in Glucocorticoid-Driven Metabolic Disorders.

    PubMed

    Moisan, Marie-Pierre; Castanon, Nathalie

    2016-01-01

    Glucocorticoid hormones (GCs) are critical for survival since they ensure the energy supply necessary to the body in an ever challenging environment. GCs are known to act on appetite, glucose metabolism, fatty acid metabolism, and storage. However, to be beneficial to the body, GC levels should be maintained in an optimal window of concentrations. Not surprisingly, conditions of GC excess or deficiency, e.g., Cushing's syndrome or Addison's disease, are associated with severe alterations of energy metabolism. Corticosteroid-binding globulin (CBG), through its high specific affinity for GCs, plays a critical role in regulating plasma GC levels and their access to target cells. Genetic studies in various species including humans have revealed that CBG is the major factor influencing interindividual genetic variability of plasma GC levels, both in basal and stress conditions. Some, but not all, of these genetic studies have also provided data linking CBG levels to body composition and insulin levels. The examination of CBG-deficient mice submitted to hyperlipidic diets unveiled specific roles for CBG in lipid storage and metabolism. An influence of CBG on appetite has not been reported but remains to be more finely analyzed. Finally, only male mice have been examined under high-fat diet, while obesity is affecting women even more than men. Overall, a role of CBG in GC-driven metabolic disorders is emerging in recent studies. Although subtle, the influence of CBG in these diseases could open the way to new therapeutic interventions since CBG is easily accessible in the blood.

  3. Modulation of Gut Microbiota in the Management of Metabolic Disorders: The Prospects and Challenges

    PubMed Central

    Erejuwa, Omotayo O.; Sulaiman, Siti A.; Ab Wahab, Mohd S.

    2014-01-01

    The gut microbiota plays a number of important roles including digestion, metabolism, extraction of nutrients, synthesis of vitamins, prevention against pathogen colonization, and modulation of the immune system. Alterations or changes in composition and biodiversity of the gut microbiota have been associated with many gastrointestinal tract (GIT) disorders such as inflammatory bowel disease and colon cancer. Recent evidence suggests that altered composition and diversity of gut microbiota may play a role in the increased prevalence of metabolic diseases. This review article has two main objectives. First, it underscores approaches (such as probiotics, prebiotics, antimicrobial agents, bariatric surgery, and weight loss strategies) and their prospects in modulating the gut microbiota in the management of metabolic diseases. Second, it highlights some of the current challenges and discusses areas of future research as it relates to the gut microbiota and metabolic diseases. The prospect of modulating the gut microbiota seems promising. However, considering that research investigating the role of gut microbiota in metabolic diseases is still in its infancy, more rigorous and well-designed in vitro, animal and clinical studies are needed. PMID:24608927

  4. Persistent disorders of mineral metabolism after one year of kidney transplantation.

    PubMed

    Gomes, Larissa Kruger; Custódio, Melani Ribeiro; Contieri, Fabiana Loss de Carvalho; Riella, Miguel C; Nascimento, Marcelo Mazza do

    2016-01-01

    The persistence of mineral metabolism disorders after renal transplant (RT) appears to possess a negative impact over graft and patient's survival. To evaluate the parameters of mineral metabolism and the persistence of hyperparathyroidism (HPT) in transplanted patients for a 12-month period after the procedure. Retrospective analysis of 41 transplants (18 women- 44%, mean age of 39 ± 15 years) performed in a University Hospital, evaluating changes of calcium (Ca), phosphorus (P) and parathyroid hormone (PTH) and the prevalence of persistent HPT. The patients were divided into two groups accordingly to PTH levels prior to Tx: Group 1 with PTH ≤ 300 pg/mL (n = 21) and Group 2 with PTH > 300 pg/mL (n = 20). The persistency of HPT after transplant was defined as PTH ≥ 100 pg/mL. The evolution of biochemical parameters and the persistency of HPT were analyzed in each group after 1 year of transplant. After a one-year of follow up, 5% of the patients presented hypophosphatemia (p < 2.7 mg/dL), 24% hypercalcemia (Ca > 10.2 mg/dL) and 48% persistency of HPT (PTH ≥ 100 pg/mL). There was a positive correlation between the PTH pre and post Tx (r = 0.42/p = 0.006) and a negative correlation between PTH and Ca pre-Tx (r = -0.45/p = 0.002). However, there was no significant difference among groups 1 and 2 regarding PTH levels pre and post Tx. The findings in this article suggest that mineral metabolism alterations and the persistency of HPT may occur after one year of renal Tx, mainly in patients which present high PTH levels prior toTx. A persistência de distúrbios do metabolismo mineral ósseo após o transplante renal (Tx) parece possuir um impacto negativo sobre a sobrevida do enxerto e do paciente. avaliar os parâmetros do metabolismo mineral e a persistência de hiperparatiroidismo (pHPT) 12 meses após o Tx. Análise retrospectiva de 41 transplantes (18 mulheres- 44%, idade de 39 ± 15 anos) realizados em um Hospital Universitário, avaliando cálcio (Ca), f

  5. Increased calcium absorption from synthetic stable amorphous calcium carbonate: double-blind randomized crossover clinical trial in postmenopausal women.

    PubMed

    Vaisman, Nachum; Shaltiel, Galit; Daniely, Michal; Meiron, Oren E; Shechter, Assaf; Abrams, Steven A; Niv, Eva; Shapira, Yami; Sagi, Amir

    2014-10-01

    Calcium supplementation is a widely recognized strategy for achieving adequate calcium intake. We designed this blinded, randomized, crossover interventional trial to compare the bioavailability of a new stable synthetic amorphous calcium carbonate (ACC) with that of crystalline calcium carbonate (CCC) using the dual stable isotope technique. The study was conducted in the Unit of Clinical Nutrition, Tel Aviv Sourasky Medical Center, Israel. The study population included 15 early postmenopausal women aged 54.9 ± 2.8 (mean ± SD) years with no history of major medical illness or metabolic bone disorder, excess calcium intake, or vitamin D deficiency. Standardized breakfast was followed by randomly provided CCC or ACC capsules containing 192 mg elemental calcium labeled with 44Ca at intervals of at least 3 weeks. After swallowing the capsules, intravenous CaCl2 labeled with 42Ca on was administered on each occasion. Fractional calcium absorption (FCA) of ACC and CCC was calculated from the 24-hour urine collection following calcium administration. The results indicated that FCA of ACC was doubled (± 0.96 SD) on average compared to that of CCC (p < 0.02). The higher absorption of the synthetic stable ACC may serve as a more efficacious way of calcium supplementation. © 2014 American Society for Bone and Mineral Research.

  6. Calcium, Magnesium, and Phosphorus Metabolism, and Parathyroid- Calcitonin Function during Prolonged Exposure to Elevated CO2 Concentrations on Submarines

    DTIC Science & Technology

    1975-12-01

    renal regulation, determine acid- base balance. calcitonin activity calcium excretion chronic hypercapnia magnesium parathyroid phosphorus...Mg increased. An important aspect of acid- base and electrolyte balance is the renal handling of an acid load. Figure 2 presents data on urine...E. SCHAEFER Navat Submarine Medical Research Laboratory, Naval Submarine Base , Groton, CT 06340 Messier, A. A., E. Heyder, W. R. Braithwaite, C

  7. Continued investigation of kinetic aspects of bone mineral metabolism. [determining body calcium by measuring argon after neutron irradiation

    NASA Technical Reports Server (NTRS)

    Palmer, H. E.

    1974-01-01

    The total body calcium in humans was determined by measuring expired Ar-37 after neutron irradiation. The excretion of Ar-37 from humans was found to be much slower than the excretion from rats and dogs, and to be related to the age of a person. A study of the uniformity of the Ar-37 production throughout the thickness of the body was studied using phantoms. The results indicate that it should be possible to obtain a uniformity within plus or minus 3% for the production of Ar-37 per unit of calcium by using a bilateral irradiation. New low background, large volume proportional counters were developed and constructed, for more sensitive measurement of Ar-37 in the expired air from patients. A new irradiation enclosure was developed for measuring total body calcium in rats by the Ar-37 method. With this enclosure the Ar-37 production per gram of calcium is constant with a standard deviation of plus or minus 2.8% for any size rat between 100 and 500 grams. The use of Na-22 as measure of bone replacement in the fractured femur of a dog was not successful.

  8. Endocrine disrupting chemicals in mixture and obesity, diabetes and related metabolic disorders

    PubMed Central

    Le Magueresse-Battistoni, Brigitte; Labaronne, Emmanuel; Vidal, Hubert; Naville, Danielle

    2017-01-01

    Obesity and associated metabolic disorders represent a major societal challenge in health and quality of life with large psychological consequences in addition to physical disabilities. They are also one of the leading causes of morbidity and mortality. Although, different etiologic factors including excessive food intake and reduced physical activity have been well identified, they cannot explain the kinetics of epidemic evolution of obesity and diabetes with prevalence rates reaching pandemic proportions. Interestingly, convincing data have shown that environmental pollutants, specifically those endowed with endocrine disrupting activities, could contribute to the etiology of these multifactorial metabolic disorders. Within this review, we will recapitulate characteristics of endocrine disruption. We will demonstrate that metabolic disorders could originate from endocrine disruption with a particular focus on convincing data from the literature. Eventually, we will present how handling an original mouse model of chronic exposition to a mixture of pollutants allowed demonstrating that a mixture of pollutants each at doses beyond their active dose could induce substantial deleterious effects on several metabolic end-points. This proof-of-concept study, as well as other studies on mixtures of pollutants, stresses the needs for revisiting the current threshold model used in risk assessment which does not take into account potential effects of mixtures containing pollutants at environmental doses, e.g., the real life exposure. Certainly, more studies are necessary to better determine the nature of the chemicals to which humans are exposed and at which level, and their health impact. As well, research studies on substitute products are essential to identify harmless molecules. PMID:28588754

  9. The Plasma Membrane Calcium Pump

    NASA Technical Reports Server (NTRS)

    Rasmussen, H.

    1983-01-01

    Three aspect of cellular calcium metabolism in animal cells was discussed including the importance of the plasma membrane in calcium homeostasis, experiments dealing with the actual mechanism of the calcium pump, and the function of the pump in relationship to the mitochondria and to the function of calmodulin in the intact cell.

  10. Extensive metabolic disorders are present in APC(min) tumorigenesis mice.

    PubMed

    Liu, Zhenzhen; Xiao, Yi; Zhou, Zhengxiang; Mao, Xiaoxiao; Cai, Jinxing; Xiong, Lu; Liao, Chaonan; Huang, Fulian; Liu, Zehao; Ali Sheikh, Md Sayed; Plutzky, Jorge; Huang, He; Yang, Tianlun; Duan, Qiong

    2016-05-15

    Wnt signaling plays essential role in mesenchymal stem cell (MSC) differentiation. Activation of Wnt signaling suppresses adipogenesis, but promotes osteogenesis in MSC. Adenomatous polyposis coli (APC) is a negative regulator of β-catenin and Wnt signaling activity. The mutation of APC gene leads to the activation of Wnt signaling and is responsible for tumorigenesis in APC(min) mouse; however, very few studies focused on its metabolic abnormalities. The present study reports a widespread metabolic disorder phenotype in APC(min) mice. The old APC(min) mice have decreased body weight and impaired adipogenesis, but severe hyperlipidemia, which mimic the phenotypes of Familial Adenomatous Polyposis (FAP), an inherited disease also caused by APC gene mutation in human. We found that the expression of lipid metabolism and free fat acids (FA) use genes in the white adipose tissue (WAT) of the APC(min) mice is much lower than those of control. The changed gene expression pattern may lead to the disability of circulatory lipid transportation and storage at WAT. Moreover, the APC(min) mice could not maintain the core body temperature in cold condition. PET-CT determination revealed that the BAT of APC(min) mice has significantly impaired ability to take up (18)FDG from the blood. Morphological studies identified that the brown adipocytes of APC(min) mice were filled with lipid droplets but fewer mitochondria. These results matched with the findings of impaired BAT function in APC(min) mice. Collectively, our study explores a new mechanism that explains abnormal metabolism in APC(min) mice and provides insights into studying the metabolic disorders of FAP patients. Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.

  11. High glucose intake and glycaemic level in critically ill neonates with inherited metabolic disorders of intoxication.

    PubMed

    Grimaud, Marion; de Lonlay, Pascale; Dupic, Laurent; Arnoux, Jean-Baptiste; Brassier, Anais; Hubert, Philippe; Lesage, Fabrice; Oualha, Mehdi

    2016-06-01

    To investigate glycaemic levels in critically ill neonates with inherited metabolic disorders of intoxication. Thirty-nine neonates with a median age of 7 days (0-24) were retrospectively included (urea cycle disorders (n = 18), maple syrup disease (n = 13), organic acidemias (n = 8)). Twenty-seven neonates were intubated, 21 were haemodialysed and 6 died. During the first 3 days, median total and peak blood glucose (BG) levels were 7.1 mmol/L (0.9-50) and 10 mmol/L (5.1-50), respectively. The median glucose intake rate was 11 mg/kg/min (2.7-15.9). Fifteen and 23 neonates exhibited severe hyperglycaemia (≥2 BG levels >12 mmol/L) and mild hyperglycaemia (≥2 BG levels >7 and ≤12 mmol/L), respectively. Glycaemic levels and number of hyperglycaemic neonates decreased over the first 3 days (p < 0.001) while total glucose intake rate was stable (p = 0.11). Enteral route of glucose intake was associated with a lower number of hyperglycaemic neonates (p = 0.04) and glycaemic level (p = 0.02). Hyperglycaemia is common in critically ill neonates receiving high glucose intake with inherited metabolic disorders of intoxication. Physicians should decrease the rate of total glucose intake and begin enteral feeding as quickly as possible in cases of persistent hyperglycaemia. • The risk of hyperglycaemia in the acute phase of critical illness is high. What is New: • Hyperglycaemia is common in the initial management of critically ill neonates with inherited metabolic disorders of intoxication receiving high glucose intake.

  12. Nanoscale Charge Balancing Mechanism in Calcium-Silicate-Hydrate Gels: Novel Complex Disordered Materials from First-principles

    NASA Astrophysics Data System (ADS)

    Ozcelik, Ongun; White, Claire

    Alkali-activated materials which have augmented chemical compositions as compared to ordinary Portland cement are sustainable technologies that have the potential to lower CO2 emissions associated with the construction industry. In particular, calcium-silicate-hydrate (C-S-H) gel is altered at the atomic scale due to changes in its chemical composition. Here, based on first-principles calculations, we predict a charge balancing mechanism at the molecular level in C-S-H gels when alkali atoms are introduced into their structure. This charge balancing process is responsible for the formation of novel structures which possess superior mechanical properties compared to their charge unbalanced counterparts. Different structural representations are obtained depending on the level of substitution and the degree of charge balancing incorporated in the structures. The impact of these charge balancing effects on the structures is assessed by analyzing their formation energies, local bonding environments, diffusion barriers and mechanical properties. These results provide information on the phase stability of alkali/aluminum containing C-S-H gels, shedding light on the fundamental mechanisms that play a crucial role in these complex disordered materials. We acknowledge funding from the Princeton Center for Complex Materials, a MRSEC supported by NSF.

  13. The metabolic impact of β-hydroxybutyrate on neurotransmission: Reduced glycolysis mediates changes in calcium responses and KATP channel receptor sensitivity.

    PubMed

    Lund, Trine M; Ploug, Kenneth B; Iversen, Anne; Jensen, Anders A; Jansen-Olesen, Inger

    2015-03-01

    Glucose is the main energy substrate for neurons, and ketone bodies are known to be alternative substrates. However, the capacity of ketone bodies to support different neuronal functions is still unknown. Thus, a change in energy substrate from glucose alone to a combination of glucose and β-hydroxybutyrate might change neuronal function as there is a known coupling between metabolism and neurotransmission. The purpose of this study was to shed light on the effects of the ketone body β-hydroxybutyrate on glycolysis and neurotransmission in cultured murine glutamatergic neurons. Previous studies have shown an effect of β-hydroxybutyrate on glucose metabolism, and the present study further specified this by showing attenuation of glycolysis when β-hydroxybutyrate was present in these neurons. In addition, the NMDA receptor-induced calcium responses in the neurons were diminished in the presence of β-hydroxybutyrate, whereas a direct effect of the ketone body on transmitter release was absent. However, the presence of β-hydroxybutyrate augmented transmitter release induced by the KATP channel blocker glibenclamide, thus giving an indirect indication of the involvement of KATP channels in the effects of ketone bodies on transmitter release. Energy metabolism and neurotransmission are linked and involve ATP-sensitive potassium (KATP ) channels. However, it is still unclear how and to what degree available energy substrate affects this link. We investigated the effect of changing energy substrate from only glucose to a combination of glucose and R-β-hydroxybutyrate in cultured neurons. Using the latter combination, glycolysis was diminished, NMDA receptor-induced calcium responses were lower, and the KATP channel blocker glibenclamide caused a higher transmitter release. © 2014 International Society for Neurochemistry.

  14. Dysregulation of neural calcium signaling in Alzheimer disease, bipolar disorder and schizophrenia

    PubMed Central

    Berridge, Michael J.

    2013-01-01

    Neurons have highly developed Ca2+ signaling systems responsible for regulating a large number of neural functions such as the control of brain rhythms, information processing and the changes in synaptic plasticity that underpin learning and memory. The tonic excitatory drive, which is activated by the ascending arousal system, is particularly important for processes such as sensory perception, cognition and consciousness. The Ca2+ signaling pathway is a key component of this arousal system that regulates the neuronal excitability responsible for controlling the neural brain rhythms required for information processing and cognition. Dysregulation of the Ca2+ signaling pathway responsible for many of these neuronal processes has been implicated in the development of some of the major neural diseases in man such as Alzheimer disease, bipolar disorder and schizophrenia. Various treatments, which are known to act by reducing the activity of Ca2+ signaling, have proved successful in alleviating the symptoms of some of these neural diseases. PMID:22895098

  15. Impact of sleep-disordered breathing on metabolic dysfunctions in patients with polycystic ovary syndrome.

    PubMed

    Chatterjee, Bidisha; Suri, Jyotsna; Suri, Jagdish Chander; Mittal, Pratima; Adhikari, Tulsi

    2014-12-01

    Polycystic ovary syndrome (PCOS) is the most common endocrinological disorder among women in the reproductive age group. These women are prone to develop sleep-disordered breathing (SDB) and metabolic disorders. SDB is also associated with metabolic dysfunctions. We hypothesized that SDB is an independent risk factor contributing to metabolic dysfunctions in women with PCOS. Prospective cross-sectional study in which 50 women with PCOS and not on any treatment were selected. They were divided into two groups: Group 1 - PCOS with SDB and Group 2 - PCOS without SDB. Thirty-three (66%) women with PCOS had SDB. Women in Group 1 had significantly higher systolic blood pressure (SBP) (P = 0.002); diastolic blood pressure (DBP) (P = 0.044); fasting blood sugar (P = 0.006), triglyceride levels (P = 0.014) and mean Ferriman-Gallwey score (P = 0.028). The HDL was significantly lower in group 1 (P = 0.006). In group 1, 42.4% of women had metabolic syndrome (P < 0.001). Excessive daytime sleepiness (EDS) was significantly higher in Group 1 (P = 0.04). Respiratory distress index significantly correlated positively with waist circumference (r = 0.551, P < 0.001), SBP (r = 0.455, P = 0.001), DBP (r = 0.387, P = 0.006), FBS (r = 0.524, P = 0.000), homeostatic model assessment (r = 0.512, P = 0.000), triglycerides (r = 0.384, P = 0.006), free testosterone (r = 0.390, P = 0.005), and negatively with HDL (r = -0.555, P < 0.001). Women with PCOS and SDB had significantly increased metabolic abnormalities as well as more severe hyperandrogenism. Women with PCOS who have metabolic abnormalities or severe hyperandrogenism should undergo an overnight PSG. Copyright © 2014 Elsevier B.V. All rights reserved.

  16. Metabolic Stress and Disorders Related to Alterations in Mitochondrial Fission or Fusion

    PubMed Central

    Babbar, Mansi; Sheikh, M. Saeed

    2014-01-01

    Mitochondrial morphology and metabolism play an important role in cellular homeostasis. Recent studies have shown that the fidelity of mitochondrial morphology is important in maintaining mitochondrial shape, number, size, membrane potential, ATP synthesis, mtDNA, motility, signaling, quality control, response to cellular stress, mitophagy and apoptosis. This article provides an overview of the current state of knowledge of the fission and fusion machinery with a focus on the mechanisms underlying the regulation of the mitochondrial morphology and cellular energy state. Several lines of evidence indicate that dysregulation of mitochondrial fission or fusion is associated with mitochondrial dysfunction, which in turn impacts mitophagy and apoptosis. Metabolic disorders are also associated with dysregulation of fission or fusion and the available lines of evidence point to a bidirectional interplay between the mitochondrial fission or fusion reactions and bioenergetics. Clearly, more in-depth studies are needed to fully elucidate the mechanisms that control mitochondrial fission and fusion. It is envisioned that the outcome of such studies will improve the understanding of the molecular basis of related metabolic disorders and also facilitate the development of better therapeutics. PMID:24533171

  17. Designing medical foods for inherited metabolic disorders: why intact protein is superior to amino acids.

    PubMed

    Ney, Denise Marie; Etzel, Mark Raymond

    2017-04-01

    Phenylketonuria and tyrosinemia are inherited metabolic disorders characterized by high blood levels of phenylalanine (Phe) or tyrosine (Tyr), due to mutations in genes affecting Phe and Tyr metabolism, respectively. The primary management is a lifelong diet restricted in protein from natural foods in combination with medical foods comprised mixtures of synthetic amino acids. Compliance is often poor after childhood leading to neuropsychological sequela. Glycomacropeptide, an intact 64 amino acid glycophosphopeptide isolated from cheese whey, provides a new paradigm for the management of phenylketonuria and tyrosinemia because glycomacropeptide contains no Phe and Tyr in its pure form, and is also a prebiotic. Medical foods made from glycomacropeptide have been used successfully for the management of phenylketonuria and tyrosinemia. Preclinical and clinical studies demonstrate that intact protein from glycomacropeptide provides a more acceptable and physiologic source of defined protein compared to amino acids in medical foods. For example, harmful gut bacteria were reduced, beneficial short chain fatty acids increased, renal workload decreased, protein utilization increased, and bone fragility decreased using intact protein versus amino acids. Advances in biotechnology will propel the transition from synthetic amino acids to intact proteins for the management of inherited metabolic disorders. Copyright © 2016 Elsevier Ltd. All rights reserved.

  18. The Role of Vaspin in the Development of Metabolic and Glucose Tolerance Disorders and Atherosclerosis

    PubMed Central

    Dimova, Rumyana; Tankova, Tsvetalina

    2015-01-01

    In recent years, most research efforts have been focused on studying insulin-sensitizing adipokines. One of the most recently discovered adipokines is vaspin, a visceral adipose tissue-derived serine protease inhibitor. Vaspin levels have been found significantly increased in mice with obesity and insulin resistance. It has been assumed that vaspin serves as an insulin sensitizer with anti-inflammatory effects and might act as a compensatory mechanism in response to decreased insulin sensitivity. Most studies in humans have shown a positive correlation between vaspin gene expression and serum levels, and metabolic syndrome parameters. Vaspin gene expression is influenced by age and gender, and the administration of insulin sensitizers enhances it in mice, whereas the use of metformin decreases serum vaspin levels in humans, probably due to different regulatory mechanisms. Presumably vaspin plays local and endocrine role in the development of initial and advanced atherosclerosis in obese subjects and might be used as a predictor of coronary and cerebrovascular disease. It is believed that vaspin could be regarded as a new link between obesity and related metabolic disorders, including glucose intolerance. The entire understanding of vaspin intimate mechanism of action might enable the development of novel etiology-based treatment strategies, targeting metabolic and glucose tolerance disorders. PMID:25945347

  19. Effect of alternative pathway therapy on branched chain amino acid metabolism in urea cycle disorder patients.

    PubMed

    Scaglia, Fernando; Carter, Susan; O'Brien, William E; Lee, Brendan

    2004-04-01

    Urea cycle disorders (UCDs) are a group of inborn errors of hepatic metabolism caused by the loss of enzymatic activities that mediate the transfer of nitrogen from ammonia to urea. These disorders often result in life-threatening hyperammonemia and hyperglutaminemia. A combination of sodium phenylbutyrate and sodium phenylacetate/benzoate is used in the clinical management of children with urea cycle defects as a glutamine trap, diverting nitrogen from urea synthesis to alternatives routes of excretion. We have observed that patients treated with these compounds have selective branched chain amino acid (BCAA) deficiency despite adequate dietary protein intake. However, the direct effect of alternative therapy on the steady state levels of plasma branched chain amino acids has not been well characterized. We have measured steady state plasma branched chain and other essential non-branched chain amino acids in control subjects, untreated ornithine transcarbamylase deficiency females and treated null activity urea cycle disorder patients in the fed steady state during the course of stable isotope studies. Steady-state leucine levels were noted to be significantly lower in treated urea cycle disorder patients when compared to either untreated ornithine transcarbamylase deficiency females or control subjects (P<0.0001). This effect was reproduced in control subjects who had depressed leucine levels when treated with sodium phenylacetate/benzoate (P<0.0001). Our studies suggest that this therapeutic modality has a substantial impact on the metabolism of branched chain amino acids in urea cycle disorder patients. These findings suggest that better titration of protein restriction could be achieved with branched chain amino acid supplementation in patients with UCDs who are on alternative route therapy.

  20. Selfish brain and selfish immune system interplay: A theoretical framework for metabolic comorbidities of mood disorders.

    PubMed

    Yamagata, Ana Sayuri; Mansur, Rodrigo Barbachan; Rizzo, Lucas Bortolotto; Rosenstock, Tatiana; McIntyre, Roger S; Brietzke, Elisa

    2017-01-01

    According to the "selfish brain" theory, the brain regulates its own energy supply influencing the peripheral metabolism and food intake according to its needs. The immune system has been likewise "selfish" due to independent energy consumption; and it may compete with the brain (another high energy-consumer) for glucose. In mood disorders, stress in mood episodes or physiological stress activate homeostasis mechanisms from the brain and the immune system to solve the imbalance. The interaction between the selfish brain and the selfish immune system may explain various conditions of medical impairment in mood disorders, such as Metabolic Syndrome (MetS), obesity, type 2 diabetes mellitus (T2DM) and immune dysregulation. The objective of this study is to comprehensively review the literature regarding the competition between the brain and the immune system for energy substrate. Targeting the energetic regulation of the brain and the immune system and their cross-talk open alternative treatments and a different approach in the study of general medical comorbidities in mood disorders, although more investigation is needed. Copyright © 2016 Elsevier Ltd. All rights reserved.

  1. Creatine metabolism and psychiatric disorders: Does creatine supplementation have therapeutic value?

    PubMed Central

    Allen, Patricia J.

    2012-01-01

    Athletes, body builders, and military personnel use dietary creatine as an ergogenic aid to boost physical performance in sports involving short bursts of high-intensity muscle activity. Lesser known is the essential role creatine, a natural regulator of energy homeostasis, plays in brain function and development. Creatine supplementation has shown promise as a safe, effective, and tolerable adjunct to medication for the treatment of brain-related disorders linked with dysfunctional energy metabolism, such as Huntington’s Disease and Parkinson’s Disease. Impairments in creatine metabolism have also been implicated in the pathogenesis of psychiatric disorders, leaving clinicians, researchers and patients alike wondering if dietary creatine has therapeutic value for treating mental illness. The present review summarizes the neurobiology of the creatine-phosphocreatine circuit and its relation to psychological stress, schizophrenia, mood and anxiety disorders. While present knowledge of the role of creatine in cognitive and emotional processing is in its infancy, further research on this endogenous metabolite has the potential to advance our understanding of the biological bases of psychopathology and improve current therapeutic strategies. PMID:22465051

  2. Creatine metabolism and psychiatric disorders: Does creatine supplementation have therapeutic value?

    PubMed

    Allen, Patricia J

    2012-05-01

    Athletes, body builders, and military personnel use dietary creatine as an ergogenic aid to boost physical performance in sports involving short bursts of high-intensity muscle activity. Lesser known is the essential role creatine, a natural regulator of energy homeostasis, plays in brain function and development. Creatine supplementation has shown promise as a safe, effective, and tolerable adjunct to medication for the treatment of brain-related disorders linked with dysfunctional energy metabolism, such as Huntington's Disease and Parkinson's Disease. Impairments in creatine metabolism have also been implicated in the pathogenesis of psychiatric disorders, leaving clinicians, researchers and patients alike wondering if dietary creatine has therapeutic value for treating mental illness. The present review summarizes the neurobiology of the creatine-phosphocreatine circuit and its relation to psychological stress, schizophrenia, mood and anxiety disorders. While present knowledge of the role of creatine in cognitive and emotional processing is in its infancy, further research on this endogenous metabolite has the potential to advance our understanding of the biological bases of psychopathology and improve current therapeutic strategies. Copyright © 2012 Elsevier Ltd. All rights reserved.

  3. Kinetic activity, membrane mitochondrial potential, lipid peroxidation, intracellular pH and calcium of frozen/thawed bovine spermatozoa treated with metabolic enhancers.

    PubMed

    Boni, R; Gallo, A; Cecchini, S

    2017-01-01

    Owing to the progressive decline of sperm motility during storage there is a need to find substances capable of enhancing sperm energy metabolism and motility and/or preserving it from oxidative damage. The aim of this study was to evaluate in frozen/thawed bovine spermatozoa the effect of several compounds, such as myo-inositol, pentoxifylline, penicillamine + hypotaurine + epinephrine mixture (PHE), caffeine and coenzyme Q10+ zinc + d-aspartate mixture (CZA), on either kinetic or metabolic parameters. Sperm kinetics was evaluated by Sperm Class Analyser whereas specific fluorochromes were used to evaluated mitochondrial membrane potential (MMP), intracellular pH, intracellular calcium concentration and lipid peroxidation. Lipid peroxidation was also evaluated by TBARS analysis. Treatments significantly affected total and progressive motility with different dynamics in relation to the incubation time. After the first hour of incubation, CZA treatment produced the best performance in total and progressive sperm motility as well as in curvilinear velocity, average path velocity and amplitude of head displacement, whereas pentoxifylline stimulated the highest straight-line velocity. MMP showed higher values (p < 0.01) after treatment with pentoxifylline and PHE. Intracytoplasmic calcium concentration and lipid peroxidation were significantly (p < 0.05) affected by the incubation time rather than the treatments. Intracellular pH varied significantly (p < 0.01) in relation to either the incubation time or treatments. In particular, it showed a progressive increase throughout incubation with values in control group significantly higher than in myo-inositol, PHE, caffeine, pentoxifylline and CZA groups (7.37 ± 0.03 vs. 7.29 ± 0.03, 7.28 ± 0.03, 7.26 ± 0.03, 7.22 ± 0.03 and 7.00 ± 0.03, respectively; p < 0.01).; however, among treatments, CZA displayed the lowest values. Significant correlations were found between sperm kinetic and metabolic

  4. Exercise Effects for Children With Autism Spectrum Disorder: Metabolic Health, Autistic Traits, and Quality of Life.

    PubMed

    Toscano, Chrystiane V A; Carvalho, Humberto M; Ferreira, José P

    2018-02-01

    This study examined the effects of a 48-week exercise-based intervention on the metabolic profile, autism traits, and perceived quality of life in children with autism spectrum disorder (ASD). We randomly allocated 64 children with ASD (aged 6-12 years) to experimental ( n = 46) and control groups ( n = 18) and used multilevel regression modeling to examine responses to receiving or not receiving the intervention. The experimental group showed beneficial effects on metabolic indicators (high-density lipoprotein cholesterol, low-density lipoprotein cholesterol, and total cholesterol), autism traits, and parent-perceived quality of life. Our results provide support for exercise and physical activity, including basic coordination and strength exercises, as important therapeutic interventions for children with ASD.

  5. Metabolism

    MedlinePlus

    Metabolism refers to all the physical and chemical processes in the body that convert or use energy, ... Tortora GJ, Derrickson BH. Metabolism. In: Tortora GJ, Derrickson ... Physiology . 14th ed. Hoboken, NJ: John Wiley & Sons; 2014:chap ...

  6. Metabolism

    MedlinePlus

    ... El metabolismo Metabolism Basics Our bodies get the energy they need from food through metabolism, the chemical ... that convert the fuel from food into the energy needed to do everything from moving to thinking ...

  7. Resting regional brain metabolism in social anxiety disorder and the effect of moclobemide therapy.

    PubMed

    Doruyter, Alex; Dupont, Patrick; Taljaard, Lian; Stein, Dan J; Lochner, Christine; Warwick, James M

    2018-04-01

    While there is mounting evidence of abnormal reactivity of several brain regions in social anxiety disorder, and disrupted functional connectivity between these regions at rest, relatively little is known regarding resting regional neural activity in these structures, or how such activity is affected by pharmacotherapy. Using 2-deoxy-2-(F-18)fluoro-D-glucose positron emission tomography, we compared resting regional brain metabolism between SAD and healthy control groups; and in SAD participants before and after moclobemide therapy. Voxel-based analyses were confined to a predefined search volume. A second, exploratory whole-brain analysis was conducted using a more liberal statistical threshold. Fifteen SAD participants and fifteen matched controls were included in the group comparison. A subgroup of SAD participants (n = 11) was included in the therapy effect comparison. No significant clusters were identified in the primary analysis. In the exploratory analysis, the SAD group exhibited increased metabolism in left fusiform gyrus and right temporal pole. After therapy, SAD participants exhibited reductions in regional metabolism in a medial dorsal prefrontal region and increases in right caudate, right insula and left postcentral gyrus. This study adds to the limited existing work on resting regional brain activity in SAD and the effects of therapy. The negative results of our primary analysis suggest that resting regional activity differences in the disorder, and moclobemide effects on regional metabolism, if present, are small. While the outcomes of our secondary analysis should be interpreted with caution, they may contribute to formulating future hypotheses or in pooled analyses.

  8. Obese Patients With a Binge Eating Disorder Have an Unfavorable Metabolic and Inflammatory Profile.

    PubMed

    Succurro, Elena; Segura-Garcia, Cristina; Ruffo, Mariafrancesca; Caroleo, Mariarita; Rania, Marianna; Aloi, Matteo; De Fazio, Pasquale; Sesti, Giorgio; Arturi, Franco

    2015-12-01

    To evaluate whether obese patients with a binge eating disorder (BED) have an altered metabolic and inflammatory profile related to their eating behaviors compared with non-BED obese.A total of 115 White obese patients consecutively recruited underwent biochemical, anthropometrical evaluation, and a 75-g oral glucose tolerance test. Patients answered the Binge Eating Scale and were interviewed by a psychiatrist. The patients were subsequently divided into 2 groups according to diagnosis: non-BED obese (n = 85) and BED obese (n = 30). Structural equation modeling analysis was performed to elucidate the relation between eating behaviors and metabolic and inflammatory profile.BED obese exhibited significantly higher percentages of altered eating behaviors, body mass index (P < 0.001), waist circumference (P < 0.01), fat mass (P < 0.001), and a lower lean mass (P < 0.001) when compared with non-BED obese. Binge eating disorder obese also had a worse metabolic and inflammatory profile, exhibiting significantly lower high-density lipoprotein cholesterol levels (P < 0.05), and higher levels of glycated hemoglobin (P < 0.01), uric acid (P < 0.05), erythrocyte sedimentation rate (P < 0.001), high-sensitive C-reactive protein (P < 0.01), and white blood cell counts (P < 0.01). Higher fasting insulin (P < 0.01) and higher insulin resistance (P < 0.01), assessed by homeostasis model assessment index and visceral adiposity index (P < 0.001), were observed among BED obese. All differences remained significant after adjusting for body mass index. No significant differences in fasting plasma glucose or 2-hour postchallenge plasma glucose were found. Structural equation modeling analysis confirmed the relation between the altered eating behaviors of BED and the metabolic and inflammatory profile.Binge eating disorder obese exhibited an unfavorable metabolic and inflammatory profile, which is related to their characteristic

  9. Obese Patients With a Binge Eating Disorder Have an Unfavorable Metabolic and Inflammatory Profile

    PubMed Central

    Succurro, Elena; Segura-Garcia, Cristina; Ruffo, Mariafrancesca; Caroleo, Mariarita; Rania, Marianna; Aloi, Matteo; De Fazio, Pasquale; Sesti, Giorgio; Arturi, Franco

    2015-01-01

    Abstract To evaluate whether obese patients with a binge eating disorder (BED) have an altered metabolic and inflammatory profile related to their eating behaviors compared with non-BED obese. A total of 115 White obese patients consecutively recruited underwent biochemical, anthropometrical evaluation, and a 75-g oral glucose tolerance test. Patients answered the Binge Eating Scale and were interviewed by a psychiatrist. The patients were subsequently divided into 2 groups according to diagnosis: non-BED obese (n = 85) and BED obese (n = 30). Structural equation modeling analysis was performed to elucidate the relation between eating behaviors and metabolic and inflammatory profile. BED obese exhibited significantly higher percentages of altered eating behaviors, body mass index (P < 0.001), waist circumference (P < 0.01), fat mass (P < 0.001), and a lower lean mass (P < 0.001) when compared with non-BED obese. Binge eating disorder obese also had a worse metabolic and inflammatory profile, exhibiting significantly lower high-density lipoprotein cholesterol levels (P < 0.05), and higher levels of glycated hemoglobin (P < 0.01), uric acid (P < 0.05), erythrocyte sedimentation rate (P < 0.001), high-sensitive C-reactive protein (P < 0.01), and white blood cell counts (P < 0.01). Higher fasting insulin (P < 0.01) and higher insulin resistance (P < 0.01), assessed by homeostasis model assessment index and visceral adiposity index (P < 0.001), were observed among BED obese. All differences remained significant after adjusting for body mass index. No significant differences in fasting plasma glucose or 2-hour postchallenge plasma glucose were found. Structural equation modeling analysis confirmed the relation between the altered eating behaviors of BED and the metabolic and inflammatory profile. Binge eating disorder obese exhibited an unfavorable metabolic and inflammatory profile, which is related to their

  10. Glutaric Aciduria Type I: A Rare Metabolic Disorder Mimicking as Choreoathetoid Cerebral Palsy

    PubMed Central

    Sarangi, Pradosh Kumar; Sahoo, Lulup Kumar; Mallick, Ashok Kumar; Dash, Prafulla Kumar

    2017-01-01

    Glutaric aciduria type I (GA I) is an autosomal recessive inborn error of metabolism caused by a deficiency of the enzyme glutaryl-CoA dehydrogenase. This disorder is characterized by progressive dystonia, choreoathetosis, and dyskinesia. It is often misdiagnosed as athetoid cerebral palsy. Laboratory evaluation usually demonstrates increased urinary excretion of gluataric acid and 3-hydroxyglutaric acid. We report a case of a 7-year-old boy presenting with choreoathetosis and dystonia, mimicking as choreoathetoid cerebral palsy. The presence of characteristic neuroimaging and biochemical studies led to the diagnosis of GA I. PMID:28553392

  11. Glutaric Aciduria Type I: A Rare Metabolic Disorder Mimicking as Choreoathetoid Cerebral Palsy.

    PubMed

    Sarangi, Pradosh Kumar; Sahoo, Lulup Kumar; Mallick, Ashok Kumar; Dash, Prafulla Kumar

    2017-01-01

    Glutaric aciduria type I (GA I) is an autosomal recessive inborn error of metabolism caused by a deficiency of the enzyme glutaryl-CoA dehydrogenase. This disorder is characterized by progressive dystonia, choreoathetosis, and dyskinesia. It is often misdiagnosed as athetoid cerebral palsy. Laboratory evaluation usually demonstrates increased urinary excretion of gluataric acid and 3-hydroxyglutaric acid. We report a case of a 7-year-old boy presenting with choreoathetosis and dystonia, mimicking as choreoathetoid cerebral palsy. The presence of characteristic neuroimaging and biochemical studies led to the diagnosis of GA I.

  12. Urea cycle disorders: a life-threatening yet treatable cause of metabolic encephalopathy in adults.

    PubMed

    Blair, Nicholas F; Cremer, Philip D; Tchan, Michel C

    2015-02-01

    Urea cycle disorders are inborn errors of metabolism that, in rare cases, can present for the first time in adulthood. We report a perplexing presentation in a woman 4 days postpartum of bizarre and out-of-character behaviour interspersed with periods of complete normality. Without any focal neurological signs or abnormality on initial investigations, the diagnosis became clear with the finding of a significantly elevated plasma ammonia level, just as she began to deteriorate rapidly. She improved following intravenous dextrose and lipid emulsion, together with sodium benzoate, arginine and a protein-restricted diet. She remains well 12 months later with no permanent sequelae. Whilst this is a rare presentation of an uncommon disease, it is a treatable disorder and its early diagnosis can prevent a fatal outcome. 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.

  13. Gene Editing: A View Through the Prism of Inherited Metabolic Disorders.

    PubMed

    Davison, James

    2018-04-01

    Novel technological developments mean that gene editing - making deliberately targeted alterations in specific genes - is now a clinical reality. The inherited metabolic disorders, a group of clinically significant, monogenic disorders, provide a useful paradigm to explore some of the many ethical issues that arise from this technological capability. Fundamental questions about the significance of the genome, and of manipulating it by selection or editing, are reviewed, and a particular focus on the legislative process that has permitted the development of mitochondrial donation techniques is considered. Ultimately, decisions about what we should do with gene editing must be determined by reference to other non-genomic texts that determine what it is to be human - rather than simply to undertake gene editing because it can be done.

  14. Does Adding Intravenous Phosphorus to Parenteral Nutrition Has Any Effects on Calcium and Phosphorus Metabolism and Bone Mineral Content in Preterm Neonates?

    PubMed

    Mazouri, Ali; Khosravi, Nastaran; Bordbar, Arash; Khalesi, Nasrin; Saboute, Maryam; Taherifard, Pegah; Mirzababaee, Marjan; Ebrahimi, Mehran

    2017-06-01

    The use of parenteral nutritional supplementation of phosphorus may lead to exhibit higher plasma phosphate concentrations and less radiological features in premature neonates susceptible to osteopenia. The present study aimed to assess the beneficial effects of adding intravenous phosphorus to total parenteral nutrition (TPN) on calcium and phosphorus metabolism in preterm neonates by measuring bone mineral content. This open-labeled randomized clinical trial was conducted on premature neonates who were hospitalized at NICU. The neonates were randomly assigned to two groups received TPN with intravenous sodium glycerophosphate or Glycophos (1.5 mmol/kg/day) or TPN without sodium glycerophosphate. At the end of the four weeks of treatment, the presence of osteopenia was examined using DEXA Scan. After completing treatment protocols, the group received TPN with intravenous Glycophos had significantly lower serum alkaline phosphatase (360±60 versus 762±71, P<0.001), as well as higher serum calcium to creatinine ratio (1.6±0.3 versus 0.44±0.13, P<0.001) compared to the control group received TPN without Glycophos. Those who received TPN with intravenous Glycophos experienced more increase in bone mineral density than those in control group (0.13±0.01 versus 0.10±0.02, P<0.001). There was no significant difference in serum calcium and serum vitamin D between the case and control groups. Adding intravenous sodium glycerophosphate to TPN in premature neonates can compensate the lack of bone mineral content and help to prevent osteopenia.

  15. Abnormal transsulfuration metabolism and reduced antioxidant capacity in Chinese children with autism spectrum disorders.

    PubMed

    Han, Yu; Xi, Qian-qian; Dai, Wei; Yang, Shu-han; Gao, Lei; Su, Yuan-yuan; Zhang, Xin

    2015-11-01

    Autism spectrum disorder (ASD) is a neurological disorder that presents a spectrum of qualitative impairments in social interaction, communication, as well as restricted and stereotyped behavioral patterns, interests, and activities. Several studies have suggested that the etiology of ASD can be partly explained by oxidative stress. However, the implications of abnormal transsulfuration metabolism and oxidative stress, and their relation with ASD are still unclear. The purpose of this study was to evaluate several transsulfuration pathway metabolites in Chinese participants diagnosed with ASD, to better understand their role in the etiology of this disorder. Fifty children (39 male, 11 female) diagnosed with ASD and 50 age- and gender-matched non-ASD children (i.e., control group) were included in this study. This prospective blinded study was undertaken to assess transsulfuration and oxidative metabolites, including levels of homocysteine (Hcy), cysteine (Cys), total glutathione (tGSH), reduced glutathione (GSH), oxidized glutathione (GSSG), and glutathione ratio (GSH/GSSG). The clinical severity of ASD was evaluated with the Childhood Autism Rating Scale (CARS), and the autistic children's present behavior was measured by the Autism Behavior Checklist (ABC). The results indicated that Hcy and GSSG levels were significantly higher in children diagnosed with ASD, Cys, tGSH and GSH levels as well as the GSH/GSSG ratio showed remarkably lower values in ASD children compared to control subjects. Hcy levels correlated significantly with increasing CARS scores and GSSG levels in children with ASD. Our results suggest that an abnormal transsulfuration metabolism and reduced antioxidant capacity (i.e., hyperhomocysteinemia and increased oxidative stress), and Hcy level appears to have a potentially negative impact on clinical severity of autistic disorder. Copyright © 2015 Elsevier Ltd. All rights reserved.

  16. Calcium metabolism in cows receiving an intramuscular injection of 1,25-dihydroxyvitamin D3 combined with prostaglandin F(2alpha) closely before parturition.

    PubMed

    Yamagishi, Norio; Ayukawa, Yu; Lee, Inhyung; Oboshi, Kenji; Naito, Yoshihisa

    2005-06-01

    To determine the effect of exogenous 1,25-dihydroxyvitamin D3 [1,25(OH)2D3] combined with induced parturition on calcium (Ca) metabolism, cows received a single intramuscular injection of 1,25(OH)2D3 and prostaglandin F(2alpha) (PGF(2alpha)) closely before calving. Ten late-pregnant, multiparous Holstein cows were assigned to 1,25(OH)2D3 group (five treated with both 1,25(OH)2D3 and PGF(2alpha)) and control group (five treated with PGF(2alpha)). 1,25(OH)2D3 group showed an increase in plasma Ca concentration around parturition, whereas control group revealed a decrease in plasma Ca level. Plasma Ca concentration in 1,25(OH)2D3 group were significantly higher than that in control group during -0.5 to 3 days after parturition.

  17. Calcium pyrophosphate dihydrate gout and other crystal deposition diseases.

    PubMed

    Reginato, A J

    1991-08-01

    The number of crystal or birefringent particles associated with arthritis is increasing, and a uniform taxonomy is needed. The term gout has been proposed as a generic term for these diseases based on historical, clinical, and crystallographic reasons. Calcium pyrophosphate dihydrate gout follows monosodium urate gout in frequency, and its spectrum of clinical manifestations continues to grow. Familial calcium pyrophosphate dihydrate gout was described for the first time in kindreds studied in England and Tunisia; new Jewish and Spanish kindreds were also reported. Type I collagen was shown to nucleate nativelike calcium pyrophosphate dihydrate crystals, and pyrophosphate elaboration was explored in cartilage explants in an attempt to reproduce the in vivo metabolic or endocrine disorders associated with calcium pyrophosphate dihydrate gout. The effect of pyrophosphatase and different cofactors such as magnesium in dissolving calcium pyrophosphate dihydrate crystals was investigated. High-resolution electron microscopy was used to study the interrelation between apatite and other basic calcium phosphate crystals in apatite gout. Raman microscopy was applied for the first time to identify crystals in biologic specimens. A simple and specific technique for basic calcium phosphate crystal identification is necessary to understand the relationship between different calcium phosphate crystals and osteoarthritis. Several reports about children and young patients with primary oxalate gout described the effect of oxalate on eyes, periodontal tissues, and bone. Multicenter studies showed poor results of renal transplantation, but favored combined liver and renal transplantation.(ABSTRACT TRUNCATED AT 250 WORDS)

  18. Tissue-dependent cerebral energy metabolism in adolescents with bipolar disorder.

    PubMed

    Dudley, Jonathan; DelBello, Melissa P; Weber, Wade A; Adler, Caleb M; Strakowski, Stephen M; Lee, Jing-Huei

    2016-02-01

    To investigate tissue-dependent cerebral energy metabolism by measuring high energy phosphate levels in unmedicated adolescents diagnosed with bipolar I disorder. Phosphorus-31 magnetic resonance spectroscopic imaging data were acquired over the entire brain of 24 adolescents with bipolar I disorder and 19 demographically matched healthy comparison adolescents. Estimates of phosphocreatine (PCr) and adenosine triphosphate (ATP, determined from the γ-resonance) in homogeneous gray and white matter in the right and left hemispheres of the cerebrum of each subject were obtained by extrapolation of linear regression analyses of metabolite concentrations vs. voxel gray matter fractions. Multivariate analyses of variance showed a significant effect of group on high energy phosphate concentrations in the right cerebrum (p=0.0002) but not in the left (p=0.17). Post-hoc testing in the right cerebrum revealed significantly reduced concentrations of PCr in gray matter and ATP in white matter in both manic (p=0.002 and 0.0001, respectively) and euthymic (p=0.004 and 0.002, respectively) bipolar I disorder subjects relative to healthy comparisons. The small sample sizes yield relatively low statistical power between manic and euthymic groups; cross-sectional observations limit the ability to determine if these findings are truly independent of mood state. Our results suggest bioenergetic impairment - consistent with downregulation of creatine kinase - is an early pathophysiological feature of bipolar I disorder. Copyright © 2015 Elsevier B.V. All rights reserved.

  19. Metabolic flexibility of mitochondrial respiratory chain disorders predicted by computer modelling.

    PubMed

    Zieliński, Łukasz P; Smith, Anthony C; Smith, Alexander G; Robinson, Alan J

    2016-11-01

    Mitochondrial respiratory chain dysfunction causes a variety of life-threatening diseases affecting about 1 in 4300 adults. These diseases are genetically heterogeneous, but have the same outcome; reduced activity of mitochondrial respiratory chain complexes causing decreased ATP production and potentially toxic accumulation of metabolites. Severity and tissue specificity of these effects varies between patients by unknown mechanisms and treatment options are limited. So far most research has focused on the complexes themselves, and the impact on overall cellular metabolism is largely unclear. To illustrate how computer modelling can be used to better understand the potential impact of these disorders and inspire new research directions and treatments, we simulated them using a computer model of human cardiomyocyte mitochondrial metabolism containing over 300 characterised reactions and transport steps with experimental parameters taken from the literature. Overall, simulations were consistent with patient symptoms, supporting their biological and medical significance. These simulations predicted: complex I deficiencies could be compensated using multiple pathways; complex II deficiencies had less metabolic flexibility due to impacting both the TCA cycle and the respiratory chain; and complex III and IV deficiencies caused greatest decreases in ATP production with metabolic consequences that parallel hypoxia. Our study demonstrates how results from computer models can be compared to a clinical phenotype and used as a tool for hypothesis generation for subsequent experimental testing. These simulations can enhance understanding of dysfunctional mitochondrial metabolism and suggest new avenues for research into treatment of mitochondrial disease and other areas of mitochondrial dysfunction. Copyright © 2016 The Authors. Published by Elsevier B.V. All rights reserved.

  20. Patients taking medications for bipolar disorder are more prone to metabolic syndrome than Korea's general population.

    PubMed

    Lee, Nam Young; Kim, Se Hyun; Cho, Belong; Lee, Yeon Ji; Chang, Jae Seung; Kang, Ung Gu; Kim, Yong Sik; Ahn, Yong Min

    2010-10-01

    Despite growing concerns about the co-morbidity of metabolic syndrome (MetS) and bipolar disorder, few studies have been conducted on this topic in Asian populations. This study examined Korean patients with bipolar disorder to assess its co-morbidity with MetS and to compare the prevalence of MetS in patients with medication for bipolar disorder with that of healthy patients. We used cross-sectional data from the medical records of patients with bipolar disorder who presented to the psychiatric clinic in Seoul National University Hospital between June 2007 and June 2008. The control group, matched for age and gender, was randomly drawn from visitors to the Health Promotion Center at the same hospital during the same period. We compared the prevalence of MetS between these two groups with independent sample t-tests and chi-squared tests. We also calculated the indirectly standardized prevalence ratio (ISPR) with a standardization that used the Fourth Korean National Health and Nutrition Examination Survey (KNHNES, 2007). The prevalence of MetS in patients who took medication for bipolar disorder (N=152) was 27.0%, 25.0% and 25.7%, based on the definitions of the American Heart Association and the National Heart, Lung and Blood Institute's adaptation of the Adult Treatment Panel III (AHA), the National Cholesterol Education Program for Adult Treatment Panel III (ATPIII) and the International Diabetes Federation (IDF), respectively. The present study determined that the prevalence of MetS was significantly higher in patients with bipolar disorder than in the control group; the odds ratios (OR) (95% CI) were 2.44 (1.35-4.40), 2.48 (1.34-4.59) and 2.57 (1.40-4.74), based on the definition of the AHA, ATPIII and IDF, respectively. The ISPR (95% CI) was 1.48 (1.02-1.93), 1.54 (1.05-2.03) and 1.98 (1.36-2.60), respectively. Patients with medications for bipolar disorder showed a significantly higher prevalence of increased waist circumference, elevated triglycerides, and

  1. Breast milk feeding in infants with inherited metabolic disorders other than phenylketonuria - a 10-year single-center experience.

    PubMed

    Pichler, Karin; Michel, Miriam; Zlamy, Manuela; Scholl-Buergi, Sabine; Ralser, Elisabeth; Jörg-Streller, Monika; Karall, Daniela

    2017-04-01

    Published data on breast milk feeding in infants suffering from inherited metabolic disorders (IMDs) other than phenylketonuria (PKU) are limited and described outcome is variable. We aimed to evaluate retrospectively whether breastfeeding and/or breast milk feeding are feasible in infants with IMDs including organic acidemias, fatty acid oxidation disorders, urea cycle disorders, aminoacidopathies or disorders of galactose metabolism. Data on breastfeeding and breast milk feeding as well as monitoring and neurological outcome were collected retrospectively from our database of patients with the mentioned IMD, who were followed in our metabolic center within the last 10 years. Twenty patients were included in the study, who were either breast fed on demand or received expressed breast milk. All the infants were evaluated clinically and biochemically at 2-4-week intervals, with weight gain as the leading parameter to determine metabolic control. Good metabolic control and adequate neurological development were achieved in all patients but one, who experienced the only metabolic crisis observed within the study period. Breast milk feeding with close clinical and biochemical monitoring is feasible in most IMD and should be considered as it offers nutritional and immunological benefits.

  2. Improvement of metabolic disorders by an EP2 receptor agonist via restoration of the subcutaneous adipose tissue in pulmonary emphysema.

    PubMed

    Tsuji, Takao; Yamaguchi, Kazuhiro; Kikuchi, Ryota; Nakamura, Hiroyuki; Misaka, Ryoichi; Nagai, Atsushi; Aoshiba, Kazutetsu

    2017-05-01

    Chronic obstructive pulmonary disease (COPD) is often associated with co-morbidities. Metabolic disorders like hyperlipidemia and diabetes occur also in underweight COPD patients, although the mechanism is uncertain. Subcutaneous adipose tissue (SAT) plays an important role in energy homeostasis, since restricted capacity to increase fat cell number with increase in fat cell size occurring instead, is associated with lipotoxicity and metabolic disorders. The aim of this study is to show the protective role of SAT for the metabolic disorders in pulmonary emphysema of a murine model. We found ectopic fat accumulation and impaired glucose homeostasis with wasting of SAT in a murine model of elastase-induced pulmonary emphysema (EIE mice) reared on a high-fat diet. ONO-AE1-259, a selective E-prostanoid (EP) 2 receptor agonist, improved angiogenesis and subsequently adipogenesis, and finally improved ectopic fat accumulation and glucose homeostasis with restoration of the capacity for storage of surplus energy in SAT. These results suggest that metabolic disorders like hyperlipidemia and diabetes occured in underweight COPD is partially due to the less capacity for storage of surplus energy in SAT, though the precise mechanism is uncertained. Our data pave the way for the development of therapeutic interventions for metabolic disorders in emphysema patients, e.g., use of pro-angiogenic agents targeting the capacity for storage of surplus energy in the subcutaneous adipose tissue. Copyright © 2017 Elsevier Inc. All rights reserved.

  3. Disordered APP metabolism and neurovasculature in trauma and aging: Combined risks for chronic neurodegenerative disorders.

    PubMed

    Ikonomovic, Milos D; Mi, Zhiping; Abrahamson, Eric E

    2017-03-01

    Traumatic brain injury (TBI), advanced age, and cerebral vascular disease are factors conferring increased risk for late onset Alzheimer's disease (AD). These conditions are also related pathologically through multiple interacting mechanisms. The hallmark pathology of AD consists of pathological aggregates of amyloid-β (Aβ) peptides and tau proteins. These molecules are also involved in neuropathology of several other chronic neurodegenerative diseases, and are under intense investigation in the aftermath of TBI as potential contributors to the risk for developing AD and chronic traumatic encephalopathy (CTE). The pathology of TBI is complex and dependent on injury severity, age-at-injury, and length of time between injury and neuropathological evaluation. In addition, the mechanisms influencing pathology and recovery after TBI likely involve genetic/epigenetic factors as well as additional disorders or comorbid states related to age and central and peripheral vascular health. In this regard, dysfunction of the aging neurovascular system could be an important link between TBI and chronic neurodegenerative diseases, either as a precipitating event or related to accumulation of AD-like pathology which is amplified in the context of aging. Thus with advanced age and vascular dysfunction, TBI can trigger self-propagating cycles of neuronal injury, pathological protein aggregation, and synaptic loss resulting in chronic neurodegenerative disease. In this review we discuss evidence supporting TBI and aging as dual, interacting risk factors for AD, and the role of Aβ and cerebral vascular dysfunction in this relationship. Evidence is discussed that Aβ is involved in cyto- and synapto-toxicity after severe TBI, and that its chronic effects are potentiated by aging and impaired cerebral vascular function. From a therapeutic perspective, we emphasize that in the fields of TBI- and aging-related neurodegeneration protective strategies should include preservation of

  4. Associations of metabolic disorder factors with the risk of uncontrolled hypertension: a follow-up cohort in rural China.

    PubMed

    Xiao, Jing; Hua, Tianqi; Shen, Huan; Zhang, Min; Wang, Xiao-Jian; Gao, Yue-Xia; Lu, Qinyun; Wu, Chuanli

    2017-04-07

    We evaluated how metabolic disorders affected antihypertension therapy. 2,912 rural Chinese patients with hypertension who provided blood samples, demographic and clinical data at baseline and after 1 year of antihypertension therapy were evaluated. At baseline, 1,515 patients (52.0%) were already receiving drug therapy and 11.4% of them had controlled blood pressure (BP). After 1 year, all 2,912 patients were receiving antihypertension therapy that was administered by community physicians, and 59.42% of them had controlled BP. Central obesity and abnormal triglyceride, high-density lipoprotein cholesterol, and glucose were associated with 15-70% higher risks of uncontrolled hypertension. Metabolic syndrome using the JIS criteria was associated with poor BP control (odds ratio: 1.71 and 1.54 for the baseline and follow-up datasets, respectively). The risk of uncontrolled hypertension increased with the number of metabolic disorders (p for trend <0.01). The presence of ≥3 metabolic disorder factors was associated with higher risks of poor BP control. The associations of metabolic factors and uncontrolled hypertension were stronger for the standard and modified ATP III criteria, compared to the IDF and JIS criteria. Metabolic factors were associated with less effective antihypertension therapy, and all definitions of metabolic syndrome helped identify patients with elevated risks of uncontrolled hypertension.

  5. Newborn Urinary Metabolic Signatures of Prematurity and Other Disorders: A Case Control Study.

    PubMed

    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.

  6. Biotin deprivation impairs mitochondrial structure and function and has implications for inherited metabolic disorders.

    PubMed

    Ochoa-Ruiz, Estefanía; Díaz-Ruiz, Rodrigo; Hernández-Vázquez, Alaín de J; Ibarra-González, Isabel; Ortiz-Plata, Alma; Rembao, Daniel; Ortega-Cuéllar, Daniel; Viollet, Benoit; Uribe-Carvajal, Salvador; Corella, José Ahmed; Velázquez-Arellano, Antonio

    2015-11-01

    Certain inborn errors of metabolism result from deficiencies in biotin containing enzymes. These disorders are mimicked by dietary absence or insufficiency of biotin, ATP deficit being a major effect,whose responsible mechanisms have not been thoroughly studied. Here we show that in rats and cultured cells it is the result of reduced TCA cycle flow, partly due to deficient anaplerotic biotin-dependent pyruvate carboxylase. This is accompanied by diminished flow through the electron transport chain, augmented by deficient cytochrome c oxidase (complex IV) activity with decreased cytochromes and reduced oxidative phosphorylation. There was also severe mitochondrial damage accompanied by decrease of mitochondria, associated with toxic levels of propionyl CoA as shown by carnitine supplementation studies, which explains the apparently paradoxical mitochondrial diminution in the face of the energy sensor AMPK activation, known to induce mitochondria biogenesis. This idea was supported by experiments on AMPK knockout mouse embryonic fibroblasts (MEFs). The multifactorial ATP deficit also provides a plausible basis for the cardiomyopathy in patients with propionic acidemia, and other diseases.Additionally, systemic inflammation concomitant to the toxic state might explain our findings of enhanced IL-6, STAT3 and HIF-1α, associated with an increase of mitophagic BNIP3 and PINK proteins, which may further increase mitophagy. Together our results imply core mechanisms of energy deficit in several inherited metabolic disorders.

  7. Glucose metabolism disorder in obese children assessed by continuous glucose monitoring system.

    PubMed

    Zou, Chao-Chun; Liang, Li; Hong, Fang; Zhao, Zheng-Yan

    2008-02-01

    Continuous glucose monitoring system (CGMS) can measure glucose levels at 5-minute intervals over a few days, and may be used to detect hypoglycemia, guide insulin therapy, and control glucose levels. This study was undertaken to assess the glucose metabolism disorder by CGMS in obese children. Eighty-four obese children were studied. Interstitial fluid (ISF) glucose levels were measured by CGMS for 24 hours covering the time for oral glucose tolerance test (OGTT). Impaired glucose tolerance (IGT), impaired fasting glucose (IFG), type 2 diabetic mellitus (T2DM) and hypoglycemia were assessed by CGMS. Five children failed to complete CGMS test. The glucose levels in ISF measured by CGMS were highly correlated with those in capillary samples (r=0.775, P<0.001). However, the correlation between ISF and capillary glucose levels was lower during the first hour than that in the later time period (r=0.722 vs r=0.830), and the ISF glucose levels in 69.62% of children were higher than baseline levels in the initial 1-3 hours. In 79 obese children who finished the CGMS, 2 children had IFG, 2 had IGT, 3 had IFG + IGT, and 2 had T2DM. Nocturnal hypoglycemia was noted during the overnight fasting in 11 children (13.92%). Our data suggest that glucose metabolism disorder including hyperglycemia and hypoglycemia is very common in obese children. Further studies are required to improve the precision of the CGMS in children.

  8. The Central Role of Biometals Maintains Oxidative Balance in the Context of Metabolic and Neurodegenerative Disorders

    PubMed Central

    Pokusa, Michal

    2017-01-01

    Traditionally, oxidative stress as a biological aspect is defined as an imbalance between the free radical generation and antioxidant capacity of living systems. The intracellular imbalance of ions, disturbance in membrane dynamics, hypoxic conditions, and dysregulation of gene expression are all molecular pathogenic mechanisms closely associated with oxidative stress and underpin systemic changes in the body. These also include aspects such as chronic immune system activation, the impairment of cellular structure renewal, and alterations in the character of the endocrine secretion of diverse tissues. All of these mentioned features are crucial for the correct function of the various tissue types in the body. In the present review, we summarize current knowledge about the common roots of metabolic and neurodegenerative disorders induced by oxidative stress. We discuss these common roots with regard to the way that (1) the respective metal ions are involved in the maintenance of oxidative balance and (2) the metabolic and signaling disturbances of the most important biometals, such as Mg2+, Zn2+, Se2+, Fe2+, or Cu2+, can be considered as the central connection point between the pathogenesis of both types of disorders and oxidative stress. PMID:28751933

  9. Experimental Models of Maternal Obesity and Neuroendocrine Programming of Metabolic Disorders in Offspring.

    PubMed

    Reynolds, Clare M; Segovia, Stephanie A; Vickers, Mark H

    2017-01-01

    Evidence from epidemiological, clinical, and experimental studies have clearly shown that disease risk in later life is increased following a poor early life environment, a process preferentially termed developmental programming. In particular, this work clearly highlights the importance of the nutritional environment during early development with alterations in maternal nutrition, including both under- and overnutrition, increasing the risk for a range of cardiometabolic and neurobehavioral disorders in adult offspring characterized by both adipokine resistance and obesity. Although the mechanistic basis for such developmental programming is not yet fully defined, a common feature derived from experimental animal models is that of alterations in the wiring of the neuroendocrine pathways that control energy balance and appetite regulation during early stages of developmental plasticity. The adipokine leptin has also received significant attention with clear experimental evidence that normal regulation of leptin levels during the early life period is critical for the normal development of tissues and related signaling pathways that are involved in metabolic and cardiovascular homeostasis. There is also increasing evidence that alterations in the epigenome and other underlying mechanisms including an altered gut-brain axis may contribute to lasting cardiometabolic dysfunction in offspring. Ongoing studies that further define the mechanisms between these associations will allow for identification of early risk markers and implementation of strategies around interventions that will have obvious beneficial implications in breaking a programmed transgenerational cycle of metabolic disorders.

  10. A cross-sectional study of breath acetone based on diabetic metabolic disorders.

    PubMed

    Li, Wenwen; Liu, Yong; Lu, Xiaoyong; Huang, Yanping; Liu, Yu; Cheng, Shouquan; Duan, Yixiang

    2015-02-26

    Breath acetone is a known biomarker for diabetes mellitus in breath analysis. In this work, a cross-sectional study of breath acetone based on clinical metabolic disorders of type 2 diabetes mellitus (T2DM) was carried out. Breath acetone concentrations of 113 T2DM patients and 56 apparently healthy individuals were measured at a single time point. Concentrations varied from 0.22 to 9.41 ppmv (mean 1.75 ppmv) for T2DM, which were significantly higher than those for normal controls (ranged from 0.32 to 1.96 ppmv, mean 0.72 ppmv, p = 0.008). Observations in our work revealed that breath acetone concentrations elevated to different degrees, along with the abnormality of blood glucose, glycated hemoglobin (HbA1c), triglyceride and cholesterol. Breath acetone showed obviously positive correlations with blood ketone and urine ketone. Possible metabolic relations between breath acetone and diabetic disorders were also discussed. This work aimed at giving an overall assessment of breath acetone from the perspective of clinical parameters for type 2 diabetes.

  11. Dynapenic obesity as an associated factor to lipid and glucose metabolism disorders and metabolic syndrome in older adults - Findings from SABE Study.

    PubMed

    Alexandre, Tiago da Silva; Aubertin-Leheudre, Mylène; Carvalho, Lívia Pinheiro; Máximo, Roberta de Oliveira; Corona, Ligiana Pires; Brito, Tábatta Renata Pereira de; Nunes, Daniella Pires; Santos, Jair Licio Ferreira; Duarte, Yeda Aparecida de Oliveira; Lebrão, Maria Lúcia

    2018-08-01

    There is little evidence showing that dynapenic obesity is associated with lipid and glucose metabolism disorders, high blood pressure, chronic disease and metabolic syndrome. Our aim was to analyze whether dynapenic abdominal obesity can be associated with lipid and glucose metabolism disorders, high blood pressure, metabolic syndrome and cardiovascular diseases in older adults living in São Paulo. This cross-sectional study included 833 older adults who took part of the third wave of the Health, Well-being and Aging Study in 2010. Based on waist circumference (>88 cm women and >102 cm men) and handgrip strength (<16 kg women and <26 kg men), four groups were identified: non-dynapenic/non-abdominal obese (ND/NAO), abdominal obese alone (AOA), dynapenic alone (DA) and dynapenic/abdominal obese (D/AO). Dependent variables were blood pressure, lipid profile, fasting glucose and glycated-haemoglobin, metabolic syndrome and cardiovascular diseases. Logistic regression was used to analyze the associations between dynapenia and abdominal obesity status and lipid and glucose metabolic profiles, blood pressure, cardiovascular diseases and metabolic syndrome. The fully adjusted models showed that D/AO individuals had higher prevalence of low HDL plasma concentrations (OR = 2.51, 95%CI: 1.40-4.48), hypertriglyceridemia (OR = 2.53, 95%CI: 1.43-4.47), hyperglycemia (OR = 2.05, 95%CI: 1.14-3.69), high glycated-haemoglobin concentrations (OR = 1.84, 95%CI: 1.03-3.30) and metabolic syndrome (OR = 12.39, 95%CI: 7.38-20.79) than ND/NAO. Dynapenic and D/AO individuals had higher prevalence of heart disease (OR = 2.05, 95%CI: 1.17-3.59 and OR = 1.92, 95%CI: 1.06-3.48, respectively) than ND/NAO. D/AO was associated with high prevalence of lipid and glucose metabolism disorders and metabolic syndrome while dynapenia and D/AO were associated with high prevalence of heart disease. Copyright © 2017 Elsevier Ltd and European Society for Clinical Nutrition and Metabolism

  12. Calcium and vitamin D supplementation and risk of kidney stone formation in postmenopausal women.

    PubMed

    Haghighi, Anousheh; Samimagham, Hamidreza; Gohardehi, Golnar

    2013-05-21

    Calcium and vitamin D are essential structural components of the skeletal system, which prevent osteoporosis after menopause. However, there is a controversial debate on the association between the intake of calcium and vitamin D supplements and the increased risk of formation of kidney calculi in postmenopausal women. which yet have to be confirmed. This study aimed to compare the metabolic changes after supplementation of calcium and vitamin D and examine the risk of stone formation. Fifty-three postmenopausal women referred to rheumatology clinic who had no history of kidney calculi, bone diseases (apart from osteoporosis), metabolic, and rheumatic disorders and had not been receiving calcium, diuretics and calcitonin were investigated. Renal ultrasonography and blood tests were performed and the urine calcium levels were measured for a period of 24 hours for all patients. The examinations were repeated after a 1- year period of treatment with supplemental calcium (100 mg/d) and vitamin D (400 IU/d) and compared with the data before the treatment. After 1 year, asymptomatic lithiasis was confirmed in 1 of 53 patients (1.9%) using ultrasonographic examination. No significant differences were found between the 24-hour urine and blood calcium levels before and after the treatment. Our findings showed that oral intake of calcium and vitamin D after 1 year has no effect on the urinary calcium excretion rate and the formation of kidney calculi in postmenopausal women.

  13. MICROSCOPIC METABOLISM OF CALCIUM IN BONE. IV. Ca$sup 45$ DEPOSITION AND GROWTH RATE IN CANINE OSTEONS

    SciTech Connect

    Marshall, J.H.; Jowsey, J.; Rowland, R.E.

    1959-02-01

    The Ca/sup 45/ content of individual osteons in three dogs given single intravenous injections has been measured autoradiographically and correlated with osteon canal diameter measured from microradiographs. An osteon was found to contain up to 10/sup -6/ of the injected activity, its total activity per unit length being approximately proportional to the square of its canal diameter at the time of injection. The activities observed at 12 hours or 2 weeks after injection divided by the corresponding time integral of the blood specific activity yield an accretion rate for calcium at each canal diameter such that the half-diameter time formore » the canal of an average forming osteon in a rather wide distnibution is 3 plus or minus 1 weeks, which is consistent with direct observations of osteon growth. It is concluded that the intense concentrations or in vivo-deposited Ca/sup 45/ which we have observed in canine osteons 12 hours or more after injection are due to accretion of calcium in appositional growth at approximately the specific activity measured in the large veins. The nature of the Ca/sup 45/ uptake in osteons which have completed or arrested appositional growth before injection cannot be inferred from the present data, but such uptake is here of an order of magnitude less than that due to appositional growth. Comparison of calculated blood flow with observed osteon growth rate indieates that an osteon in the early stages of appositiona« less

  14. Androgen excess and metabolic disorders in women with PCOS: beyond the body mass index.

    PubMed

    Condorelli, R A; Calogero, A E; Di Mauro, M; Mongioi', L M; Cannarella, R; Rosta, G; La Vignera, S

    2018-04-01

    Insulin resistance is a common feature among women with polycystic ovary syndrome (PCOS), especially in those patients with hyperandrogenism and chronic anovulation. PCOS women are at risk for developing metabolic syndrome, impaired glucose tolerance and type II diabetes mellitus (DM II). The aim of this review is to explore the existing knowledge of the interplay between androgen excess, pancreatic β-cell function, non-alcoholic fatty liver disease (NAFLD), intra-abdominal and subcutaneous (SC) abdominal adipocytes in PCOS, providing a better comprehension of the molecular mechanisms of diabetologic interest. A comprehensive MEDLINE ® search was performed using relevant key terms for PCOS and DM II. Insulin-induced hyperandrogenism could impair pancreatic β-cell function, the SC abdominal adipocytes' lipid storage capacity, leading to intra-abdominal adipocyte hypertrophy and lipotoxicity, which in turn promotes insulin resistance, and could enhance NAFLD. Fetal hyperandrogenism exposure prompts to metabolic disorders. Treatment with flutamide showed to partially reverse insulin resistance. Metabolic impairment seems not to be dependent only on the total fat mass content and body weight in women with PCOS and might be ascribed to the androgen excess.

  15. Natural Products to Counteract the Epidemic of Cardiovascular and Metabolic Disorders

    PubMed Central

    Šmejkal, Karel; Heiss, Elke H.; Atanasov, Atanas G.

    2016-01-01

    Natural products have always been exploited to promote health and served as a valuable source for the discovery of new drugs. In this review, the great potential of natural compounds and medicinal plants for the treatment or prevention of cardiovascular and metabolic disorders, global health problems with rising prevalence, is addressed. Special emphasis is laid on natural products for which efficacy and safety have already been proven and which are in clinical trials, as well as on plants used in traditional medicine. Potential benefits from certain dietary habits and dietary constituents, as well as common molecular targets of natural products, are also briefly discussed. A glimpse at the history of statins and biguanides, two prominent representatives of natural products (or their derivatives) in the fight against metabolic disease, is also included. The present review aims to serve as an “opening” of this special issue of Molecules, presenting key historical developments, recent advances, and future perspectives outlining the potential of natural products for prevention or therapy of cardiovascular and metabolic disease. PMID:27338339

  16. Branched-chain Amino Acids are associated with Metabolic Parameters in Bipolar Disorder.

    PubMed

    Fellendorf, F T; Platzer, M; Pilz, R; Rieger, A; Kapfhammer, H P; Mangge, H; Dalkner, N; Zelzer, S; Meinitzer, A; Birner, A; Bengesser, S A; Queissner, R; Hamm, C; Hartleb, R; Reininghaus, E Z

    2018-06-14

    An important aspect of bipolar disorder (BD) research is the identification of biomarkers pertaining to the somatic health state. The branched-chain essential amino acids (BCAAs), viz valine, leucine and isoleucine, have been proposed as biomarkers of an individual's health state, given their influence on protein synthesis and gluconeogenesis inhibition. BCAA levels of 141 euthymic/subsyndromal individuals with BD and 141 matched healthy controls (HC) were analyzed by high-pressure lipid chromatography and correlated with clinical psychiatric, anthropometric and metabolic parameters. BD and HC did not differ in valine and isoleucine, whereas leucine was significantly lower in BD. Furthermore, correlations were found between BCAAs and anthropometric and glucose metabolism data. All BCAAs correlated with lipid metabolism parameters in females. There were no associations between BCAAs and long-term clinical parameters of BD. A negative correlation was found between valine and Hamilton-Depression-Scale, and Beck-Depression-Inventory-II, in male individuals. Our results indicate the utility of BCAAs as biomarkers for the current state of health, also in BD. As BD individuals have a high risk for overweight/obesity, in association with comorbid medical conditions (e.g. cardiovascular diseases, insulin resistance), health-state markers are urgently required. However, no illness-specific associations were found in this euthymic/subsyndromal BD group.

  17. Natural molecules for the therapy of hyperandrogenism and metabolic disorders in PCOS.

    PubMed

    Cappelli, V; Musacchio, M C; Bulfoni, A; Morgante, G; De Leo, V

    2017-06-01

    Polycystic ovary syndrome (PCOS) is the most common endocrinopathy of women of reproductive age and a complex endocrine condition, due to its heterogeneity and uncertainty about its etiology. However, PCOS is also associated with other metabolic abnormalities such as insulin resistance, impaired glucose tolerance, and diabetes. There are few medications that are approved for the most common symptoms of PCOS, leading to the off-label use of medications that were approved for other indications. One of the most common medications being used off label for PCOS is metformin. Research of other effective therapeutic options has included the utility of inositol. A systematic literature search of PubMed was performed using the following combination of terms: 'PCOS', 'hyperandrogenism' 'inositol', 'natural molecules'. Only papers published between 2000 and 2016 were included in our analysis. The present review analyzes all aspects of the choice of natural molecules in the treatment of hyperandrogenism and metabolic disorders in PCOS women. The rationale underlying the use of inositols as a therapeutic application in PCOS derives from their activities as insulin mimetic agents and their salutary effects on metabolism and hyperandrogenism without side effects. In this review will discuss the role of a number of natural associations between inositol and different substances in the treatment of hyperandrogenic symptoms in PCOS women.

  18. Mechanisms by which cocoa flavanols improve metabolic syndrome and related disorders.

    PubMed

    Strat, Karen M; Rowley, Thomas J; Smithson, Andrew T; Tessem, Jeffery S; Hulver, Matthew W; Liu, Dongmin; Davy, Brenda M; Davy, Kevin P; Neilson, Andrew P

    2016-09-01

    Dietary administration of cocoa flavanols may be an effective complementary strategy for alleviation or prevention of metabolic syndrome, particularly glucose intolerance. The complex flavanol composition of cocoa provides the ability to interact with a variety of molecules, thus allowing numerous opportunities to ameliorate metabolic diseases. These interactions likely occur primarily in the gastrointestinal tract, where native cocoa flavanol concentration is high. Flavanols may antagonize digestive enzymes and glucose transporters, causing a reduction in glucose excursion, which helps patients with metabolic disorders maintain glucose homeostasis. Unabsorbed flavanols, and ones that undergo enterohepatic recycling, will proceed to the colon where they can exert prebiotic effects on the gut microbiota. Interactions with the gut microbiota may improve gut barrier function, resulting in attenuated endotoxin absorption. Cocoa may also positively influence insulin signaling, possibly by relieving insulin-signaling pathways from oxidative stress and inflammation and/or via a heightened incretin response. The purpose of this review is to explore the mechanisms that underlie these outcomes, critically review the current body of literature related to those mechanisms, explore the implications of these mechanisms for therapeutic utility, and identify emerging or needed areas of research that could advance our understanding of the mechanisms of action and therapeutic potential of cocoa flavanols. Copyright © 2016 Elsevier Inc. All rights reserved.

  19. Natural Products to Counteract the Epidemic of Cardiovascular and Metabolic Disorders.

    PubMed

    Waltenberger, Birgit; Mocan, Andrei; Šmejkal, Karel; Heiss, Elke H; Atanasov, Atanas G

    2016-06-22

    Natural products have always been exploited to promote health and served as a valuable source for the discovery of new drugs. In this review, the great potential of natural compounds and medicinal plants for the treatment or prevention of cardiovascular and metabolic disorders, global health problems with rising prevalence, is addressed. Special emphasis is laid on natural products for which efficacy and safety have already been proven and which are in clinical trials, as well as on plants used in traditional medicine. Potential benefits from certain dietary habits and dietary constituents, as well as common molecular targets of natural products, are also briefly discussed. A glimpse at the history of statins and biguanides, two prominent representatives of natural products (or their derivatives) in the fight against metabolic disease, is also included. The present review aims to serve as an "opening" of this special issue of Molecules, presenting key historical developments, recent advances, and future perspectives outlining the potential of natural products for prevention or therapy of cardiovascular and metabolic disease.

  20. N-acetylcysteine Protects Mice from High Fat Diet-induced Metabolic Disorders.

    PubMed

    Ma, Yongjie; Gao, Mingming; Liu, Dexi

    2016-08-01

    To study the effects of N-acetylcysteine (NAC, C5H9NO3S) on diet-induced obesity and obesity-related metabolic disorders. Six-week-old male C57BL/6 mice fed a chow or high-fat diet (HFD) were treated with NAC (2 g/L) in drinking water for 11 weeks. Its influences on body weight and food intake were manually measured, and influence on body composition were analyzed by magnetic residence imaging. Glucose meter and ELISA were used to determine serum glucose and insulin levels, as well as lipid content in the liver. The effects of NAC treatment on mRNA levels of genes involved in inflammation, thermogenesis, and lipid metabolism in various tissues were determined by real time PCR. NAC supplementation inhibited the increase of fat mass and the development of obesity when mice were fed an HFD. NAC treatment significantly lowered HFD-induced macrophage infiltration, and enhanced adiponectin gene expression, resulting in reduced hyperglycemia and hyperinsulinemia, and improvement of insulin resistance. NAC oral administration suppressed hepatic lipid accumulation, as evidenced by lower levels of triglyceride and cholesterol in the liver. The beneficial effects are associated with a decrease of hepatic Pparγ and its target gene expression, and an increase in the expression of genes responsible for lipid oxidation and activation of farnesoid X receptor. Furthermore, NAC treatment also stimulates expression of thermogenic genes. These results provide direct proof of the protective potential of NAC against HFD-induced obesity and obesity-associated metabolic disorders.

  1. Weight Gain and Metabolic Consequences of Risperidone in Young Children With Autism Spectrum Disorder

    PubMed Central

    Scahill, Lawrence; Jeon, Sangchoon; Boorin, Susan J.; McDougle, Christopher J.; Aman, Michael G.; Dziura, James; McCracken, James T.; Caprio, Sonia; Arnold, L. Eugene; Nicol, Ginger; Deng, Yanhong; Challa, Saankari A.; Vitiello, Benedetto

    2016-01-01

    Objective We examine weight gain and metabolic consequences of risperidone monotherapy in children with autism spectrum disorder (ASD). Method This was a 24-week, multisite, randomized trial of risperidone only versus risperidone plus parent training in 124 children (mean age 6.9 ± 2.35 years; 105 boys, 19 girls) with ASD and serious behavioral problems. We monitored height, weight, waist circumference, and adverse effects during the trial. Fasting blood samples were obtained pretreatment and at Week 16. Results In 97 patients with a mean of 22.9 ± 2.8 weeks risperidone exposure, there was a 5.4 ± 3.4 kg weight gain over 24 weeks (p < .0001); waist circumference increased from 60.7 ± 10.4 cm to 66.8 ± 11.3 cm (p <. 0001). At baseline 60.8% (59 of 97) patients were classified as having normal weight; by Week 24, only 29.4% (25 of 85) remained in that group. Growth curve analysis showed a significant change in body mass index (BMI) z-scores from pretreatment to Week 24 (p<.0001). This effect was significantly greater for patients with reported increased appetite in the first 8 weeks. From pretreatment to Week 16, there were significant increases in glucose (p=.02), hemoglobin A1c (p=.01), insulin (p <.0001), homeostatic model assessment–insulin resistance (HOMA-IR; p< .001), alanine aminotransferase (p=.01), and leptin (p < .0001). Adiponectin declined (p =.003). At baseline, 7 patients met conventional criteria for metabolic syndrome; by Week 16, 12 additional patients were so classified. Conclusion Rapid weight gain with risperidone treatment may promote the cascade of biochemical indices associated with insulin resistance and metabolic syndrome. Appetite, weight, waist circumference, liver function tests, blood lipids, and glucose warrant monitoring. Clinical trial registration information Drug and Behavioral Therapy for Children With Pervasive Developmental Disorders; http://clinicaltrials.gov/; NCT00080145 PMID:27126856

  2. Calcium Overload Accelerates Phosphate-Induced Vascular Calcification Via Pit-1, but not the Calcium-Sensing Receptor.

    PubMed

    Masumoto, Asuka; Sonou, Tomohiro; Ohya, Masaki; Yashiro, Mitsuru; Nakashima, Yuri; Okuda, Kouji; Iwashita, Yuko; Mima, Toru; Negi, Shigeo; Shigematsu, Takashi

    2017-07-01

    Vascular calcification (VC) is a risk factor of cardiovascular and all-cause mortality in patients with chronic kidney disease (CKD). CKD-mineral and bone metabolism disorder is an important problem in patients with renal failure. Abnormal levels of serum phosphate and calcium affect CKD-mineral and bone metabolism disorder and contribute to bone disease, VC, and cardiovascular disease. Hypercalcemia is a contributing factor in progression of VC in patients with CKD. However, the mechanisms of how calcium promotes intracellular calcification are still unclear. This study aimed to examine the mechanisms underlying calcium-induced calcification in a rat aortic tissue culture model. Aortic segments from 7-week-old male Sprague-Dawley rats were cultured in serum-supplemented medium for 10 days. We added high calcium (HiCa; calcium 3.0 mM) to high phosphate (HPi; phosphate 3.8 mM) medium to accelerate phosphate and calcium-induced VC. We used phosphonoformic acid and the calcimimetic R-568 to determine whether the mechanism of calcification involves Pit-1 or the calcium-sensing receptor. Medial VC was significantly augmented by HPi+HiCa medium compared with HPi alone (300%, p<0.05), and was associated with upregulation of Pit-1 protein. Pit-1 protein concentrations in HPi+HiCa medium were greater than those in HPi medium. Phosphonoformic acid completely negated the augmentation of medial VC induced by HPi+HiCa. R-568 had no additive direct effect on medial VC. These results indicated that exposure to HPi+HiCa accelerates medial VC, and this is mediated through Pit-1, not the calcium-sensing receptor.

  3. Translational research and behavioral sciences in developmental medicine: metabolic conditions of pregnancy versus autism spectrum disorders.

    PubMed

    Lopaczynski, Wlodek

    2012-01-01

    Recently, scientific literature informed that metabolic conditions in pregnant women may be associated with increased risk for autism and other neurodevelopmental disorders in their offspring. In a cohort study of more than 1000 children between the ages of 2 and 5 years, those who had mothers classified as having "metabolic conditions" (which included diabetes, hypertension, and obesity) during pregnancy were at a significantly higher risk for developing an autism spectrum disorder (ASD) and neurodevelopmental delays. In addition, mothers with obesity were 1.6 times more likely to have a child with ASD and more than twice as likely to have a child with other developmental problems. In the United States, the prevalence of obesity among women of childbearing age is 34%. Moreover, with obesity rates rising steadily, these results appear to raise serious public health implications. The main objective of this Editorial is to propagate the health care improvement based on the translation research approach from basic behavioral sciences and relevant integrative neuroscience to pressing clinical issues that include an understanding of the etiology and assessment of disorders, and the assessment of functioning and development of innovative and culturally appropriate preventive treatment. Behavioral interventions for weight management in pregnancy may include the Transtheoretical Model (TTM) employed in obese pregnant women and then, the comparison with elements of the ecological model. A comparative effectiveness design is to test the effect of tailoring while including one of the most important predictors of screening-physician recommendation: after careful selection of analyzed behaviors from the TTM approach. However, there is also a risk that the evidence may not be conclusive for sustained weigh loss as a primary outcome of the proposed intervention, although the TTM in combination of physical activity and diet tended to produce significant results. Therefore

  4. Offspring neuroimmune consequences of maternal malnutrition: Potential mechanism for behavioral impairments that underlie metabolic and neurodevelopmental disorders.

    PubMed

    Smith, B L; Reyes, T M

    2017-10-01

    Maternal malnutrition significantly increases offspring risk for both metabolic and neurodevelopmental disorders. Animal models of maternal malnutrition have identified behavioral changes in the adult offspring related to executive function and reward processing. Together, these changes in executive and reward-based behaviors likely contribute to the etiology of both metabolic and neurodevelopmental disorders associated with maternal malnutrition. Concomitant with the behavioral effects, maternal malnutrition alters offspring expression of reward-related molecules and inflammatory signals in brain pathways that control executive function and reward. Neuroimmune pathways and microglial interactions in these specific brain circuits, either in early development or later in adulthood, could directly contribute to the maternal malnutrition-induced behavioral phenotypes. Understanding these mechanisms will help advance treatment strategies for metabolic and neurodevelopmental disorders, especially noninvasive dietary supplementation interventions. Copyright © 2017 Elsevier Inc. All rights reserved.

  5. Impact of Glucose Metabolism Disorders on IGF-1 Levels in Patients with Acromegaly.

    PubMed

    Dogansen, Sema Ciftci; Yalin, Gulsah Yenidunya; Tanrikulu, Seher; Yarman, Sema

    2018-05-01

    In this study, we aimed to evaluate the presence of glucose metabolism abnormalities and their impact on IGF-1 levels in patients with acromegaly. Ninety-three patients with acromegaly (n=93; 52 males/41 females) were included in this study. Patients were separated into three groups such as; normal glucose tolerance (n=23, 25%), prediabetes (n=38, 41%), and diabetes mellitus (n=32, 34%). Insulin resistance was calculated with homeostasis model assessment (HOMA). HOMA-IR > 2.5 or ≤2.5 were defined as insulin resistant or noninsulin resistant groups, respectively. Groups were compared in terms of factors that may be associated with glucose metabolism abnormalities. IGF-1% ULN (upper limit of normal)/GH ratios were used to evaluate the impact of glucose metabolism abnormalities on IGF-1 levels. Patients with diabetes mellitus were significantly older with an increased frequency of hypertension (p<0.001, p=0.01, respectively). IGF-1% ULN/GH ratio was significantly lower in prediabetes group than in normal glucose tolerance group (p=0.04). Similarly IGF-1% ULN/GH ratio was significantly lower in insulin resistant group than in noninsulin resistant group (p=0.04). Baseline and suppressed GH levels were significantly higher in insulin resistant group than in noninsulin resistant group (p=0.024, p<0.001, respectively). IGF-1% ULN/GH ratio is a useful marker indicating glucose metabolism disorders and IGF-1 levels might be inappropriately lower in acromegalic patients with insulin resistance or prediabetes. We suggest that IGF-1 levels should be re-evaluated after the improvement of insulin resistance or glycemic regulation for the successful management of patients with acromegaly. © Georg Thieme Verlag KG Stuttgart · New York.

  6. Mangiferin Stimulates Carbohydrate Oxidation and Protects Against Metabolic Disorders Induced by High-Fat Diets

    PubMed Central

    Apontes, Pasha; Liu, Zhongbo; Su, Kai; Benard, Outhiriaradjou; Youn, Dou Y.; Li, Xisong; Li, Wei; Mirza, Raihan H.; Bastie, Claire C.; Jelicks, Linda A.; Pessin, Jeffrey E.; Muzumdar, Radhika H.; Sauve, Anthony A.

    2014-01-01

    Excessive dietary fat intake causes systemic metabolic toxicity, manifested in weight gain, hyperglycemia, and insulin resistance. In addition, carbohydrate utilization as a fuel is substantially inhibited. Correction or reversal of these effects during high-fat diet (HFD) intake is of exceptional interest in light of widespread occurrence of diet-associated metabolic disorders in global human populations. Here we report that mangiferin (MGF), a natural compound (the predominant constituent of Mangifera indica extract from the plant that produces mango), protected against HFD-induced weight gain, increased aerobic mitochondrial capacity and thermogenesis, and improved glucose and insulin profiles. To obtain mechanistic insight into the basis for these effects, we determined that mice exposed to an HFD combined with MGF exhibited a substantial shift in respiratory quotient from fatty acid toward carbohydrate utilization. MGF treatment significantly increased glucose oxidation in muscle of HFD-fed mice without changing fatty acid oxidation. These results indicate that MGF redirects fuel utilization toward carbohydrates. In cultured C2C12 myotubes, MGF increased glucose and pyruvate oxidation and ATP production without affecting fatty acid oxidation, confirming in vivo and ex vivo effects. Furthermore, MGF inhibited anaerobic metabolism of pyruvate to lactate but enhanced pyruvate oxidation. A key target of MGF appears to be pyruvate dehydrogenase, determined to be activated by MGF in a variety of assays. These findings underscore the therapeutic potential of activation of carbohydrate utilization in correction of metabolic syndrome and highlight the potential of MGF to serve as a model compound that can elicit fuel-switching effects. PMID:24848064

  7. Mangiferin stimulates carbohydrate oxidation and protects against metabolic disorders induced by high-fat diets.

    PubMed

    Apontes, Pasha; Liu, Zhongbo; Su, Kai; Benard, Outhiriaradjou; Youn, Dou Y; Li, Xisong; Li, Wei; Mirza, Raihan H; Bastie, Claire C; Jelicks, Linda A; Pessin, Jeffrey E; Muzumdar, Radhika H; Sauve, Anthony A; Chi, Yuling

    2014-11-01

    Excessive dietary fat intake causes systemic metabolic toxicity, manifested in weight gain, hyperglycemia, and insulin resistance. In addition, carbohydrate utilization as a fuel is substantially inhibited. Correction or reversal of these effects during high-fat diet (HFD) intake is of exceptional interest in light of widespread occurrence of diet-associated metabolic disorders in global human populations. Here we report that mangiferin (MGF), a natural compound (the predominant constituent of Mangifera indica extract from the plant that produces mango), protected against HFD-induced weight gain, increased aerobic mitochondrial capacity and thermogenesis, and improved glucose and insulin profiles. To obtain mechanistic insight into the basis for these effects, we determined that mice exposed to an HFD combined with MGF exhibited a substantial shift in respiratory quotient from fatty acid toward carbohydrate utilization. MGF treatment significantly increased glucose oxidation in muscle of HFD-fed mice without changing fatty acid oxidation. These results indicate that MGF redirects fuel utilization toward carbohydrates. In cultured C2C12 myotubes, MGF increased glucose and pyruvate oxidation and ATP production without affecting fatty acid oxidation, confirming in vivo and ex vivo effects. Furthermore, MGF inhibited anaerobic metabolism of pyruvate to lactate but enhanced pyruvate oxidation. A key target of MGF appears to be pyruvate dehydrogenase, determined to be activated by MGF in a variety of assays. These findings underscore the therapeutic potential of activation of carbohydrate utilization in correction of metabolic syndrome and highlight the potential of MGF to serve as a model compound that can elicit fuel-switching effects. © 2014 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.

  8. Placebo cessation in binge eating disorder: effect on anthropometric, cardiovascular, and metabolic variables.

    PubMed

    Blom, Thomas J; Guerdjikova, Anna I; Mori, Nicole; Casuto, Leah S; McElroy, Susan L

    2015-01-01

    The aim of this study was to evaluate the effects of cessation of binge eating in response to placebo treatment in binge eating disorder (BED) on anthropometric, cardiovascular, and metabolic variables. We pooled participant-level data from 10 randomized, double-blind, placebo-controlled trials of medication for BED. We then compared patients who stopped binge eating with those who did not on changes in weight, body mass index (BMI), systolic and diastolic blood pressure, pulse, and fasting lipids and glucose. Of 234 participants receiving placebo, 60 (26%) attained cessation from binge eating. Patients attaining cessation showed modestly decreased diastolic blood pressure compared with patients who continued to binge eat. Weight and BMI remained stable in patients who stopped binge eating, but increased somewhat in those who continued to binge eat. Patients who stopped binge eating with placebo had greater reductions in diastolic blood pressure and gained less weight than patients who continued to binge eat. Self-report of eating pathology in BED may predict physiologic variables. Copyright © 2014 John Wiley & Sons, Ltd and Eating Disorders Association. Copyright © 2014 John Wiley & Sons, Ltd and Eating Disorders Association.

  9. Review of transcranial photobiomodulation for major depressive disorder: targeting brain metabolism, inflammation, oxidative stress, and neurogenesis

    PubMed Central

    Cassano, Paolo; Petrie, Samuel R.; Hamblin, Michael R.; Henderson, Theodore A.; Iosifescu, Dan V.

    2016-01-01

    Abstract. We examined the use of near-infrared and red radiation (photobiomodulation, PBM) for treating major depressive disorder (MDD). While still experimental, preliminary data on the use of PBM for brain disorders are promising. PBM is low-cost with potential for wide dissemination; further research on PBM is sorely needed. We found clinical and preclinical studies via PubMed search (2015), using the following keywords: “near-infrared radiation,” “NIR,” “low-level light therapy,” “low-level laser therapy,” or “LLLT” plus “depression.” We chose clinically focused studies and excluded studies involving near-infrared spectroscopy. In addition, we used PubMed to find articles that examine the link between PBM and relevant biological processes including metabolism, inflammation, oxidative stress, and neurogenesis. Studies suggest the processes aforementioned are potentially effective targets for PBM to treat depression. There is also clinical preliminary evidence suggesting the efficacy of PBM in treating MDD, and comorbid anxiety disorders, suicidal ideation, and traumatic brain injury. Based on the data collected to date, PBM appears to be a promising treatment for depression that is safe and well-tolerated. However, large randomized controlled trials are still needed to establish the safety and effectiveness of this new treatment for MDD. PMID:26989758

  10. Alendronate and Resistive Exercise Countermeasures Against Bed Rest-Induced Bone Loss: Biochemical Markers of Bone and Calcium Metabolism

    NASA Technical Reports Server (NTRS)

    Smith, Scott M.; Nillen, Jeannie L.; Davis-Street, Janis E.; DeKerlegand, Diane E.; LeBlanc, Adrian; Shackelford, Linda C.

    2001-01-01

    Weightlessness-induced bone loss must be counteracted to ensure crew health during extendedduration space missions. Studies were conducted to assess two bone loss countermeasures in a ground-based model: horizontal bed rest. Following a 3-wk ambulatory adaptation period, male and female subjects (aged 21-56 y) completed a 17-wk bed rest protocol. Subjects were assigned to one of three treatments: alendronate (ALEN; 10 mg/d, n=6), resistive exercise (RE; 1.5 h/d, 6 d/wk, n=8), or control (CN; no countermeasure, n=8). Dietary intake was adjusted to maintain body weight. Endocrine and biochemical indices were measured in blood and urine using standard laboratory methods. All data reported are expressed as percent change from individual pre-bedrest data. Serum calcium changed little during bed rest, and tended to decrease (4-8%) in ALEN subjects. In RE subjects, bone alkaline phosphatase and osteocalcin were increased >65 and >30%, respectively, during bed rest, while these were unchanged or decreased in ALEN and CN subjects. Urinary calcium was increased 50% in CN subjects, but was unchanged or decreased in both ALEN and RE groups. Urinary n-telopeptide excretion was increased 40-50% in CN and RE subjects, but decreased 20% in ALEN subjects. Pyridinium crosslink and deoxypyridinoline excretion were increased 20-50% during bed rest. These data suggest that RE countermeasures are effective at increasing markers of bone formation in an analog of weightlessness, while ALEN reduces markers of bone resorption. Counteracting the bone loss of space flight may require both pharmacologic and exercise countermeasures.

  11. Metabolic disorders and cardiovascular risk in people living with HIV/AIDS without the use of antiretroviral therapy.

    PubMed

    Raposo, Mariana Amaral; Armiliato, Geyza Nogueira de Almeida; Guimarães, Nathalia Sernizon; Caram, Camila Abrahão; Silveira, Raíssa Domingues de Simoni; Tupinambás, Unaí

    2017-01-01

    Metabolic disorders in people living with HIV/AIDS (PLH) have been described even before the introduction of antiretroviral (ARV) drugs in the treatment of HIV infection and are risk factors for cardiovascular diseases. Based on this, the purpose of this study was to assess metabolic disorders and cardiovascular risk in PLH before the initiation of antiretroviral treatment (ART). This was a cross-sectional descriptive study of 87 PLH without the use of ART, which was carried out between January and September 2012 at a specialized infectious diseases center in Minas Gerais, Brazil. The main metabolic disorders in the population were low serum levels of HDL-cholesterol, hypertriglyceridemia and abdominal obesity. Dyslipidemia was prevalent in 62.6% of the study population, whereas metabolic syndrome (MS) was prevalent in 11.5% of patients assessed by the International Diabetes Federation (IDF) criteria and 10.8% assessed by the National Cholesterol Education Program-Adult Treatment Panel (NCEP-ATPIII) criteria. Regarding cardiovascular risk, 89.7% of the population presented a low coronary risk according to the Framingham Risk Score. A greater proportion of patients diagnosed with MS presented low cardiovascular risk (80% assessed by IDF criteria and 77.8% assessed by NCEP-ATPIII criteria). Metabolic disorders in this population may be due to HIV infection or lifestyle (smoking, sedentary lifestyle and inadequate diet). The introduction of ART can enhance dyslipidemia, increasing cardiovascular risk, especially among those who have classic risks of cardiovascular disease.

  12. Cationic Polystyrene Resolves Nonalcoholic Steatohepatitis, Obesity, and Metabolic Disorders by Promoting Eubiosis of Gut Microbiota and Decreasing Endotoxemia.

    PubMed

    Zhu, Airu; Chen, Jingjing; Wu, Pengfei; Luo, Mei; Zeng, Yilan; Liu, Yong; Zheng, Han; Zhang, Li; Chen, Zishou; Sun, Qun; Li, Wenwen; Duan, Yixiang; Su, Danmei; Xiao, Zhixiong; Duan, Zhongping; Zheng, Sujun; Bai, Li; Zhang, Xiaohui; Ju, Zhongyuan; Li, Yan; Hu, Richard; Pandol, Stephen J; Han, Yuan-Ping

    2017-08-01

    A pandemic of metabolic diseases, consisting of type 2 diabetes, nonalcoholic fatty liver disease, and obesity, has imposed critical challenges for societies worldwide, prompting investigation of underlying mechanisms and exploration of low-cost and effective treatment. In this report, we demonstrate that metabolic disorders in mice generated by feeding with a high-fat diet without dietary vitamin D can be prevented by oral administration of polycationic amine resin. Oral administration of cholestyramine, but not the control uncharged polystyrene, was able to sequester negatively charged bacterial endotoxin in the gut, leading to 1 ) reduced plasma endotoxin levels, 2 ) resolved systemic inflammation and hepatic steatohepatitis, and 3 ) improved insulin sensitivity. Gut dysbiosis, characterized as an increase of the phylum Firmicutes and a decrease of Bacteroidetes and Akkermansia muciniphila, was fully corrected by cholestyramine, indicating that the negatively charged components in the gut are critical for the dysbiosis. Furthermore, fecal bacteria transplant, derived from cholestyramine-treated animals, was sufficient to antagonize the metabolic disorders of the recipient mice. These results indicate that the negatively charged components produced by dysbiosis are critical for biogenesis of metabolic disorders and also show a potential application of cationic polystyrene to treat metabolic disorders through promoting gut eubiosis. © 2017 by the American Diabetes Association.

  13. Calcium Carbonate

    MedlinePlus

    ... Maalox® (as a combination product containing Calcium Carbonate, Simethicone) ... Relief (as a combination product containing Calcium Carbonate, Simethicone) ... Plus (as a combination product containing Calcium Carbonate, Simethicone)

  14. Role of calcium supplementation during pregnancy in reducing risk of developing gestational hypertensive disorders: a meta-analysis of studies from developing countries

    PubMed Central

    2011-01-01

    Background Hypertension in pregnancy stand alone or with proteinuria is one of the leading causes of maternal mortality and morbidity in the world. Epidemiological and clinical studies have shown that an inverse relationship exists between calcium intake and development of hypertension in pregnancy though the effect varies based on baseline calcium intake and pre-existing risk factors. The purpose of this review was to evaluate preventive effect of calcium supplementation during pregnancy on gestational hypertensive disorders and related maternal and neonatal mortality in developing countries. Methods A literature search was carried out on PubMed, Cochrane Library and WHO regional databases. Data were extracted into a standardized excel sheet. Identified studies were graded based on strengths and limitations of studies. All the included studies were from developing countries. Meta-analyses were generated where data were available from more than one study for an outcome. Primary outcomes were maternal mortality, eclampsia, pre-eclampsia, and severe preeclampsia. Neonatal outcomes like neonatal mortality, preterm birth, small for gestational age and low birth weight were also evaluated. We followed standardized guidelines of Child Health Epidemiology Reference Group (CHERG) to generate estimates of effectiveness of calcium supplementation during pregnancy in reducing maternal and neonatal mortality in developing countries, for inclusion in the Lives Saved Tool (LiST). Results Data from 10 randomized controlled trials were included in this review. Pooled analysis showed that calcium supplementation during pregnancy was associated with a significant reduction of 45% in risk of gestational hypertension [Relative risk (RR) 0.55; 95 % confidence interval (CI) 0.36-0.85] and 59% in the risk of pre-eclampsia [RR 0.41; 95 % CI 0.24-0.69] in developing countries. Calcium supplementation during pregnancy was also associated with a significant reduction in neonatal mortality

  15. Metabolic Disorder in Chronic Obstructive Pulmonary Disease (COPD) Patients: Towards a Personalized Approach Using Marine Drug Derivatives

    PubMed Central

    Lamonaca, Palma; Prinzi, Giulia; Kisialiou, Aliaksei; Cardaci, Vittorio; Fini, Massimo; Russo, Patrizia

    2017-01-01

    Metabolic disorder has been frequently observed in chronic obstructive pulmonary disease (COPD) patients. However, the exact correlation between obesity, which is a complex metabolic disorder, and COPD remains controversial. The current study summarizes a variety of drugs from marine sources that have anti-obesity effects and proposed potential mechanisms by which lung function can be modulated with the anti-obesity activity. Considering the similar mechanism, such as inflammation, shared between obesity and COPD, the study suggests that marine derivatives that act on the adipose tissues to reduce inflammation may provide beneficial therapeutic effects in COPD subjects with high body mass index (BMI). PMID:28335527

  16. Metabolic Disorder in Chronic Obstructive Pulmonary Disease (COPD) Patients: Towards a Personalized Approach Using Marine Drug Derivatives.

    PubMed

    Lamonaca, Palma; Prinzi, Giulia; Kisialiou, Aliaksei; Cardaci, Vittorio; Fini, Massimo; Russo, Patrizia

    2017-03-20

    Metabolic disorder has been frequently observed in chronic obstructive pulmonary disease (COPD) patients. However, the exact correlation between obesity, which is a complex metabolic disorder, and COPD remains controversial. The current study summarizes a variety of drugs from marine sources that have anti-obesity effects and proposed potential mechanisms by which lung function can be modulated with the anti-obesity activity. Considering the similar mechanism, such as inflammation, shared between obesity and COPD, the study suggests that marine derivatives that act on the adipose tissues to reduce inflammation may provide beneficial therapeutic effects in COPD subjects with high body mass index (BMI).

  17. Chronic exposure to low concentrations of lead induces metabolic disorder and dysbiosis of the gut microbiota in mice.

    PubMed

    Xia, Jizhou; Jin, Cuiyuan; Pan, Zihong; Sun, Liwei; Fu, Zhengwei; Jin, Yuanxiang

    2018-08-01

    Lead (Pb) is one of the most prevalent toxic, nonessential heavy metals that can contaminate food and water. In this study, effects of chronic exposure to low concentrations of Pb on metabolism and gut microbiota were evaluated in mice. It was observed that exposure of mice to 0.1mg/L Pb, supplied via drinking water, for 15weeks increased hepatic TG and TCH levels. The levels of some key genes related to lipid metabolism in the liver increased significantly in Pb-treated mice. For the gut microbiota, at the phylum level, the relative abundance of Firmicutes and Bacteroidetes changed obviously in the feces and the cecal contents of mice exposed to 0.1mg/L Pb for 15weeks. In addition, 16s rRNA gene sequencing further discovered that Pb exposure affected the structure and richness of the gut microbiota. Moreover, a 1 H NMR metabolic analysis unambiguously identified 31 metabolites, and 15 metabolites were noticeably altered in 0.1mg/L Pb-treated mice. Taken together, the data indicate that chronic Pb exposure induces dysbiosis of the gut microbiota and metabolic disorder in mice. Chronic Pb exposure induces metabolic disorder, dysbiosis of the gut microbiota and hepatic lipid metabolism disorder in mice. Copyright © 2018 Elsevier B.V. All rights reserved.

  18. The impact of race on metabolic disease risk factors in women with and without posttraumatic stress disorder.

    PubMed

    Dedert, Eric A; Harper, Leia A; Calhoun, Patrick S; Dennis, Michelle F; Beckham, Jean C

    2013-03-01

    The literature on PTSD and metabolic disease risk factors has been limited by lacking investigation of the potential influence of commonly comorbid disorders and the role of race. In this study data were provided by a sample of 134 women (63 PTSD and 71 without PTSD). Separate sets of models examining associations of psychiatric disorder classifications with metabolic disease risk factors were used. Each model included race (African American or Caucasian), psychiatric disorder, and their interaction. There was an interaction of race and PTSD on body mass index, abdominal obesity, and triglycerides. While PTSD was not generally associated with deleterious health effects in African American participants, PTSD was related to worse metabolic disease risk factors in Caucasians. MDD was associated with metabolic disease risk factors, but there were no interactions with race. Results support the importance of race in the relationship between PTSD and metabolic disease risk factors. Future research would benefit from analysis of cultural factors to explain how race might influence metabolic disease risk factors in PTSD.

  19. Metabolic syndrome in patients with bipolar disorder: comparison with major depressive disorder and non-psychiatric controls.

    PubMed

    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, p<0.001), also when adjusted for sociodemographic and lifestyle factors (OR 1.52, 95% CI: 1.09-2.12, p=0.02 compared to MDD; OR 1.79, 95% CI: 1.20-2.67, p=0.005 compared to non-psychiatric controls). The differences 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.

  20. MECHANISMS IN ENDOCRINOLOGY: Nutrition as a mediator of oxidative stress in metabolic and reproductive disorders in women.

    PubMed

    Diamanti-Kandarakis, Evanthia; Papalou, Olga; Kandaraki, Eleni A; Kassi, Georgia

    2017-02-01

    Nutrition can generate oxidative stress and trigger a cascade of molecular events that can disrupt oxidative and hormonal balance. Nutrient ingestion promotes a major inflammatory and oxidative response at the cellular level in the postprandial state, altering the metabolic state of tissues. A domino of unfavorable metabolic changes is orchestrated in the main metabolic organs, including adipose tissue, skeletal muscle, liver and pancreas, where subclinical inflammation, endothelial dysfunction, mitochondrial deregulation and impaired insulin response and secretion take place. Simultaneously, in reproductive tissues, nutrition-induced oxidative stress can potentially violate delicate oxidative balance that is mandatory to secure normal reproductive function. Taken all the above into account, nutrition and its accompanying postprandial oxidative stress, in the unique context of female hormonal background, can potentially compromise normal metabolic and reproductive functions in women and may act as an active mediator of various metabolic and reproductive disorders. © 2017 European Society of Endocrinology.

  1. [Association of lipid metabolism disorder with peritoneum transport ability and mortality in peritoneal dialysis patients].

    PubMed

    Fang, Yan-hui; Jiang, Lan-ping; Zhou, Zi-juan; Wang, Hai-yun; Xu, Hong; Li, Xue-mei; Chen, Li-meng; Li, Xue-wang

    2013-06-01

    To observe the features of lipid metabolism disorders of peritoneal dialysis(PD)patients and hemodialysis(HD)patients and explore the association of lipid metabolism disorder with peritoneum transport ability and mortality. The clinical data of 127 PD patients and 95 HD patients who had received regular dialysis for more than 3 months in Peking Union Medical College Hospital since March 2009 were retrospectively analyzed.Serum lipid profiles were tested.Serum hypersensitive C reactive protein(hsCRP)was examined by immune turbidimetric method.Serum carbohydrate antigen 125(CA125)and iPTH were detected by electrochemical luminescence method.Peritoneum transport ability was evaluated through peritoneal equilibration test(PET).After a 2-year follow-up,the levels of CA125 and the peritoneum transport abilities were compared between the baseline data and the end point,and the relationship between lipid disorder and the mortality was analyzed. After the 2-year follow-up,25(19.7%)PD patients died.The leading cause of death was congestive heart failure(56.0%),followed by myocardial infarction(12.0%),septic shock(12.0%),respiratory failure(8.0%),asphyxiation(8.0%),and gastrointestinal bleeding(4.0%).Compared with the survivors,the death patients were older(P=0.005),with significant lower albumin level(P=0.000)and pre-albumin level(P=0.001).However,there was no significant difference in other clinical features including body mass index(BMI),blood pressure,dialysis time,nPCR,iPTH,hemoglobin,hsCRP,and serum lipid level(all P>0.05).COX regression analysis showed that diabetes mellitus(P=0.030)and mean SBP(P=0.048)were significantly associated with the mortality of PD patients.At the baseline,the CA125 level in patients with high,high average,and low average transport status of peritoneum was(38.02±64.37),(21.21±19.41),and(17.55±23.2)U/ml,respectively(P=0.09).There was no association between the transport status and lipid(TC,TG and LDL). Congestive heart failure is the leading

  2. Compared effects of calcium and sodium polystyrene sulfonate on mineral and bone metabolism and volume overload in pre-dialysis patients with hyperkalemia.

    PubMed

    Nakayama, Yosuke; Ueda, Kaoru; Yamagishi, Sho-Ichi; Sugiyama, Miki; Yoshida, Chika; Kurokawa, Yuka; Nakamura, Nao; Moriyama, Tomofumi; Kodama, Goh; Minezaki, Tomohisa; Ito, Sakuya; Nagata, Akiko; Taguchi, Kensei; Yano, Junko; Kaida, Yusuke; Shibatomi, Kazutaka; Fukami, Kei

    2018-02-01

    Hyperkalemia is prevalent in end-stage renal disease patients, being involved in life-threatening arrhythmias. Although polystyrene sulfonate (PS) is commonly used for the treatment of hyperkalemia, direct comparison of effects between calcium and sodium PS (CPS and SPS) on mineral and bone metabolism has not yet been studied. In a randomized and crossover design, 20 pre-dialysis patients with hyperkalemia (>5 mmol/l) received either oral CPS or SPS therapy for 4 weeks. After 4-week treatments, there was no significant difference of changes in serum potassium (K) from the baseline (ΔK) between the two groups. However, SPS significantly decreased serum calcium (Ca) and magnesium (Mg) and increased intact parathyroid hormone (iPTH) values, whereas CPS reduced iPTH. ΔiPTH was inversely correlated with ΔCa and ΔMg (r = -0.53 and r = -0.50, respectively). Furthermore, sodium (Na) and atrial natriuretic peptide (ANP) levels were significantly elevated in patients with SPS, but not with CPS, whereas ΔNa and ΔANP were significantly correlated with each other in all the patients. We also found that ΔNa and Δ(Na to chloride ratio) were positively correlated with ΔHCO 3 - . In artificial colon fluid, CPS increased Ca and decreased Na. Furthermore, SPS greatly reduced K, Mg, and NH 3 . Compared with SPS, CPS may be safer for the treatment of hyperkalemia in pre-dialysis patients, because it did not induce hyperparathyroidism or volume overload.

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

    PubMed

    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. Genetic disorders of vitamin B12 metabolism: eight complementation groups – eight genes

    PubMed Central

    Froese, D. Sean; Gravel, Roy A.

    2010-01-01

    Vitamin B12 (cobalamin, Cbl) is an essential nutrient in human metabolism. Genetic diseases of vitamin B12 utilisation constitute an important fraction of inherited newborn disease. Functionally, B12 is the cofactor for methionine synthase and methylmalonyl CoA mutase. To function as a cofactor, B12 must be metabolised through a complex pathway that modifies its structure and takes it through subcellular compartments of the cell. Through the study of inherited disorders of vitamin B12 utilisation, the genes for eight complementation groups have been identified, leading to the determination of the general structure of vitamin B12 processing and providing methods for carrier testing, prenatal diagnosis and approaches to treatment. PMID:21114891

  5. The role of cholesterol metabolism and various steroid abnormalities in autism spectrum disorders: A hypothesis paper

    PubMed Central

    Gillberg, Christopher; Fernell, Elisabeth; Kočovská, Eva; Minnis, Helen; Bourgeron, Thomas; Thompson, Lucy

    2017-01-01

    Based on evidence from the relevant research literature, we present a hypothesis that there may be a link between cholesterol, vitamin D, and steroid hormones which subsequently impacts on the development of at least some of the “autisms” [Coleman & Gillberg]. Our hypothesis, driven by the peer reviewed literature, posits that there may be links between cholesterol metabolism, which we will refer to as “steroid metabolism” and findings of steroid abnormalities of various kinds (cortisol, testosterone, estrogens, progesterone, vitamin D) in autism spectrum disorder (ASD). Further research investigating these potential links is warranted to further our understanding of the biological mechanisms underlying ASD. Autism Res 2017. © 2017 The Authors Autism Research published by Wiley Periodicals, Inc. on behalf of International Society for Autism Research. Autism Res 2017, 10: 1022–1044. © 2017 International Society for Autism Research, Wiley Periodicals, Inc. PMID:28401679

  6. Design and Synthesis of Novel Arctigenin Analogues for the Amelioration of Metabolic Disorders

    PubMed Central

    2015-01-01

    Analogues of the natural product (−)-arctigenin, an activator of adenosine monophosphate activated protein kinase, were prepared in order to evaluate their effects on 2-deoxyglucose uptake in L6 myotubes and possible use in ameliorating metabolic disorders. Racemic arctigenin 2a was found to display a similar uptake enhancement as does (−)-arctigenin. As a result, the SAR study was conducted utilizing racemic compounds. The structure–activity relationship study led to the discovery of key substitution patterns on the lactone motif that govern 2-deoxyglucose uptake activities. The results show that replacement of the para-hydroxyl group of the C-2 benzyl moiety of arctigenin by Cl has a pronounced effect on uptake activity. Specifically, analogue 2p, which contains the p-Cl substituent, stimulates glucose uptake and fatty acid oxidation in L6 myotubes. PMID:25941553

  7. Design and synthesis of novel arctigenin analogues for the amelioration of metabolic disorders.

    PubMed

    Duan, Shudong; Huang, Suling; Gong, Jian; Shen, Yu; Zeng, Limin; Feng, Ying; Ren, Wenming; Leng, Ying; Hu, Youhong

    2015-04-09

    Analogues of the natural product (-)-arctigenin, an activator of adenosine monophosphate activated protein kinase, were prepared in order to evaluate their effects on 2-deoxyglucose uptake in L6 myotubes and possible use in ameliorating metabolic disorders. Racemic arctigenin 2a was found to display a similar uptake enhancement as does (-)-arctigenin. As a result, the SAR study was conducted utilizing racemic compounds. The structure-activity relationship study led to the discovery of key substitution patterns on the lactone motif that govern 2-deoxyglucose uptake activities. The results show that replacement of the para-hydroxyl group of the C-2 benzyl moiety of arctigenin by Cl has a pronounced effect on uptake activity. Specifically, analogue 2p, which contains the p-Cl substituent, stimulates glucose uptake and fatty acid oxidation in L6 myotubes.

  8. Association between suicidal behaviour and impaired glucose metabolism in depressive disorders.

    PubMed

    Koponen, Hannu; Kautiainen, Hannu; Leppänen, Esa; Mäntyselkä, Pekka; Vanhala, Mauno

    2015-07-22

    Disturbances in lipid metabolism have been linked to suicidal behaviour, but little is known about the association between suicide risk and abnormal glucose metabolism in depression. Hyperglycaemia and hyperinsulinaemia may increase the risk of depression and also the risk for suicide, we therefore studied associations between suicidal behaviour and disturbances in glucose metabolism in depressive patients who had been referred to depression nurse case managers. Patients aged 35 years and older (N = 448, mean age 51 years) who were experiencing a new depressive episode, who were referred to depression nurse case managers in 2008-2009 and who scored ≥10 on the Beck Depression Inventory were enrolled in this study. The study was conducted in municipalities within the Central Finland Hospital District (catchment area of 274 000 inhabitants) as part of the Finnish Depression and Metabolic Syndrome in Adults study. The patients' psychiatric diagnoses and suicidal behaviour were confirmed by the Mini-International Neuropsychiatric Interview. Blood samples, for glucose and lipid determinations, were drawn from participants after 12 h of fasting, which was followed by a 2-hour oral glucose tolerance test (OGTT) when blood was drawn at 0 and 2 h. Insulin resistance was measured by the Quantitative Insulin Sensitivity Check Index (QUICKI) method. Suicidal ideation (49 %) and previous suicide attempts (16 %) were common in patients with major depressive disorder or dysthymia. Patients with depression and suicidal behaviour had higher blood glucose concentrations at baseline and at 2 hours in the OGTT. Glucose levels associated positively with the prevalence of suicidal behaviour, and the linearity was significant at baseline (p for linearity: 0.012, adjusted for age and sex) and for 2-hour OGTT glucose (p for linearity: 0.004, adjusted for age and sex). QUICKI levels associated with suicidal behavior (p for linearity across tertiles of QUICKI: 0.026). Total and LDL

  9. Porcine models for the metabolic syndrome, digestive and bone disorders: a general overview.

    PubMed

    Litten-Brown, J C; Corson, A M; Clarke, L

    2010-06-01

    The aim of this review article is to provide an overview of the role of pigs as a biomedical model for humans. The usefulness and limitations of porcine models have been discussed in terms of metabolic, cardiovascular, digestive and bone diseases in humans. Domestic pigs and minipigs are the main categories of pigs used as biomedical models. One drawback of minipigs is that they are in short supply and expensive compared with domestic pigs, which in contrast cost more to house, feed and medicate. Different porcine breeds show different responses to the induction of specific diseases. For example, ossabaw minipigs provide a better model than Yucatan for the metabolic syndrome as they exhibit obesity, insulin resistance and hypertension, all of which are absent in the Yucatan. Similar metabolic/physiological differences exist between domestic breeds (e.g. Meishan v. Pietrain). The modern commercial (e.g. Large White) domestic pig has been the preferred model for developmental programming due to the 2- to 3-fold variation in body weight among littermates providing a natural form of foetal growth retardation not observed in ancient (e.g. Meishan) domestic breeds. Pigs have been increasingly used to study chronic ischaemia, therapeutic angiogenesis, hypertrophic cardiomyopathy and abdominal aortic aneurysm as their coronary anatomy and physiology are similar to humans. Type 1 and II diabetes can be induced in swine using dietary regimes and/or administration of streptozotocin. Pigs are a good and extensively used model for specific nutritional studies as their protein and lipid metabolism is comparable with humans, although pigs are not as sensitive to protein restriction as rodents. Neonatal and weanling pigs have been used to examine the pathophysiology and prevention/treatment of microbial-associated diseases and immune system disorders. A porcine model mimicking various degrees of prematurity in infants receiving total parenteral nutrition has been established to

  10. The use of antioxidants to prevent glutamate-induced derangement of calcium ion metabolism in rat cerebral cortex synaptosomes.

    PubMed

    Avrova, N F; Shestak, K I; Zakharova, I O; Sokolova, T V; Tyurina, Y Y; Tyurin, V A

    2000-01-01

    Glutamate is shown to induce increases in intracellular Ca2+ concentrations ([Ca2+]i), increases in 45Ca2+ influx, decreases in the activity of Na+,K+-ATPase activity, and activation of the Na+/Ca2+ exchanger in rat cerebral cortex synaptosomes. NMDA receptor antagonists virtually prevented these effects. Preincubation of synaptosomes with alpha-tocopherol, superoxide dismutase, and ganglioside GM1 normalized [Ca2+]i, 45Ca2+ influx, and Na+,K+-ATPase activity in rat cerebral cortex synaptosomes exposed to glutamate. Glutamate and GM1 activated the Na+/K+ exchanger, and their effects were additive. Calcium ions entering cerebral cortex nerve cells via NMDA receptors during exposure to high glutamate concentrations appeared to be only the trigger for the processes activating free-radical reactions. Activation of these reactions led to increases in Ca2+ influx into cells, decreases in Na+,K+-ATPase activity, and significant increases in [Ca2+]i, though this could be prevented by antioxidants and gangliosides.

  11. Calciphylaxis: a devastating complication of derangements of calcium-phosphorus metabolism--a case report and review of the literature.

    PubMed

    Carter, Trish; Ratnam, Shobha

    2013-01-01

    Calciphylaxis is a rare and potentially devastating condition also referred to as uremic gangrene syndrome, calcific uremic arteriolopathy, metastatic calcification, and uremic small-vessel disease that can present in patients with end stage renal disease. This article reports a case of a 38-year-old African-American female on peritoneal dialysis for six years with a known history of non-adherence with diet, medications, and prescribed peritoneal dialysis treatment regimen. At her monthly clinic visit, the patient complained of burning sensation in the fingers of both hands with limited fine motor movement due to edema and severe pain. A presumptive diagnosis of calciphylaxis led to hospital admission with confirmation by X-ray of her hands. The patient was switched to hemodialysis with low calcium dialysate, aggressive reduction in phosphorus, diet counseling, use of cinacalcet, and six weeks of intravenous sodium thiosulfate infusion with hemodialysis treatments. The patient's condition improved with resolution of symptoms. This case was chosen based on the rarity of a calciphylaxis presentation and paucity of knowledge regarding diagnosis and treatment.

  12. Effect of cytokine antibodies in the immunomodulation of inflammatory response and metabolic disorders induced by scorpion venom.

    PubMed

    Taibi-Djennah, Zahida; Laraba-Djebari, Fatima

    2015-07-01

    Androctonus australis hector (Aah) venom and its neurotoxins may affect the neuro-endocrine immunological axis due to their binding to ionic channels of axonal membranes. This binding leads to the release of neurotransmitters and immunological mediators accompanied by pathophysiological effects. Although the hyperglycemia induced by scorpion venom is clearly established, the involved mediators in these deregulations are unknown. The strong relationship between inflammation and the wide variety of physiological processes can suggest that the activation of the inflammatory response and the massive release of IL-6 and TNF-α release induced by the venom may induce hyperglycemia and various biological disorders. We therefore investigated in this study the contribution of IL-6 and TNF-α in the modulation of inflammatory response and metabolic disorder induced by Aah venom. Obtained results revealed that Aah venom induced inflammatory response characterized by significant increase of inflammatory cells in sera and tissues homogenates accompanied by hyperglycemia and hyperinsulinemia, suggesting that the venom induced insulin resistance. It also induced severe alterations in hepatic parenchyma associated to metabolic disorders and imbalanced redox status. Cytokine antagonists injected 30 min prior to Aah venom allowed a significant reduction of inflammatory biomarker and plasma glucose levels, they also prevented metabolic disorders, oxidative stress and hepatic tissue damage induced by Aah venom. In conclusion, IL-6 and TNF-α appear to play a crucial role in the inflammatory response, hyperglycemia and associated complications to glucose metabolism disorders (carbohydrate and fat metabolism disorders, oxidative stress and hepatic damage) observed following scorpion envenoming. Copyright © 2014 Elsevier B.V. All rights reserved.

  13. Sleep duration and disorders in pregnancy: implications for glucose metabolism and pregnancy outcomes

    PubMed Central

    O’Keeffe, M; St-Onge, M-P

    2013-01-01

    Humans have an innate requirement for sleep that is intrinsically governed by circadian and endocrine systems. More recently, reduced sleep duration has gained significant attention for its possible contribution to metabolic dysfunction. Significant evidence suggests that reduced sleep duration may elevate the risk for impaired glucose functioning, insulin resistance and type 2 diabetes. However, to date, few studies have determined the implications of reduced sleep duration with regard to glucose control during pregnancy. With the high prevalence of overweight and obesity in women of reproductive age, the occurrence of gestational diabetes mellitus (GDM) is increasing. GDM results in elevated risk of maternal and fetal complications, as well as increased risk of type 2 diabetes postpartum. Infants born to women with GDM also carry a life-long risk of obesity and type 2 diabetes. The impact of reduced sleep on glucose management during pregnancy has not yet been fully assessed and a paucity of literature currently exits. Herein, we review the association between reduced sleep and impaired carbohydrate metabolism and propose how reduced sleep during pregnancy may result in further dysfunction of the carbohydrate axis. A particular focus will be given to sleep-disordered breathing, as well as GDM-complicated pregnancies. Putative mechanisms of action by which reduced sleep may adversely affect maternal and infant outcomes are also discussed. Finally, we will outline important research questions that need to be addressed. PMID:22945608

  14. Maternal Obesity and Developmental Programming of Metabolic Disorders in Offspring: Evidence from Animal Models

    PubMed Central

    Li, M.; Sloboda, D. M.; Vickers, M. H.

    2011-01-01

    The incidence of obesity and overweight has reached epidemic proportions in the developed world as well as in those countries transitioning to first world economies, and this represents a major global health problem. Concern is rising over the rapid increases in childhood obesity and metabolic disease that will translate into later adult obesity. Although an obesogenic nutritional environment and increasingly sedentary lifestyle contribute to our risk of developing obesity, a growing body of evidence links early life nutritional adversity to the development of long-term metabolic disorders. In particular, the increasing prevalence of maternal obesity and excess maternal weight gain has been associated with a heightened risk of obesity development in offspring in addition to an increased risk of pregnancy-related complications. The mechanisms that link maternal obesity to obesity in offspring and the level of gene-environment interactions are not well understood, but the early life environment may represent a critical window for which intervention strategies could be developed to curb the current obesity epidemic. This paper will discuss the various animal models of maternal overnutrition and their importance in our understanding of the mechanisms underlying altered obesity risk in offspring. PMID:21969822

  15. Potential of nor-Ursodeoxycholic Acid in Cholestatic and Metabolic Disorders.

    PubMed

    Trauner, Michael; Halilbasic, Emina; Claudel, Thierry; Steinacher, Daniel; Fuchs, Claudia; Moustafa, Tarek; Pollheimer, Marion; Krones, Elisabeth; Kienbacher, Christian; Traussnigg, Stefan; Kazemi-Shirazi, Lili; Munda, Petra; Hofer, Harald; Fickert, Peter; Paumgartner, Gustav

    2015-01-01

    24-nor-ursodeoxycholic acid (norUDCA) is a side-chain shortened derivate of ursodeoxycholic acid (UDCA). Since norUDCA is only ineffectively conjugated with glycine or taurine, it has specific physicochemical and therapeutic properties distinct from UDCA. Nonamidated norUDCA undergoes cholehepatic shunting enabling 'ductular targeting' and inducing a bicarbonate-rich hypercholeresis, with cholangioprotective effects. At the same time it has direct anti-inflammatory, antilipotoxic, anti fibrotic, and antiproliferative properties targeting various liver cell populations. norUDCA appears to be one of the most promising novel treatment approaches targeting the liver and the bile duct system at multifactorial and multicellular levels. This review article is a summary of a lecture given at the XXIII International Bile Acid Meeting (Falk Symposium 194) on 'Bile Acids as Signal Integrators and Metabolic Modulators' held in Freiburg, October 8-9, 2014, and summarizes the recent progress with norUDCA as a novel therapeutic approach in cholestatic and metabolic (liver) disorders. 2015 S. Karger AG, Basel.

  16. Metabolically based liver damage pathophysiology in patients with urea cycle disorders - A new hypothesis.

    PubMed

    Ivanovski, Ivan; Ješić, Miloš; Ivanovski, Ana; Garavelli, Livia; Ivanovski, Petar

    2017-11-28

    The underlying pathophysiology of liver dysfunction in urea cycle disorders (UCDs) is still largely elusive. There is some evidence that the accumulation of urea cycle (UC) intermediates are toxic for hepatocyte mitochondria. It is possible that liver injury is directly caused by the toxicity of ammonia. The rarity of UCDs, the lack of checking of iron level in these patients, superficial knowledge of UC and an underestimation of the metabolic role of fumaric acid, are the main reasons that are responsible for the incomprehension of the mechanism of liver injury in patients suffering from UCDs. Owing to our routine clinical practice to screen for iron overload in severely ill neonates, with the focus on the newborns suffering from acute liver failure, we report a case of citrullinemia with neonatal liver failure and high blood parameters of iron overload. We hypothesize that the key is in the decreased-deficient fumaric acid production in the course of UC in UCDs that causes several sequentially intertwined metabolic disturbances with final result of liver iron overload. The presented hypothesis could be easily tested by examining the patients suffering from UCDs, for liver iron overload. This could be easily performed in countries with a high population and comprehensive national register for inborn errors of metabolism. Providing the hypothesis is correct, neonatal liver damage in patients having UCD can be prevented by the supplementation of pregnant women with fumaric or succinic acid, prepared in the form of iron supplementation pills. After birth, liver damage in patients having UCDs can be prevented by supplementation of these patients with zinc fumarate or zinc succinylate, as well.

  17. Maternal lipopolysaccharide exposure results in glucose metabolism disorders and sex hormone imbalance in male offspring.

    PubMed

    Zhao, Mei; Yuan, Li; Yuan, Man-Man; Huang, Li-Li; Su, Chang; Chen, Yuan-Hua; Yang, Yu-Ying; Hu, Yan; Xu, De-Xiang

    2018-04-01

    An adverse intrauterine environment may be an important factor contributing to the development of type 2 diabetes in later life. The present study investigated the longitudinal effects of maternal lipopolysaccharide (LPS) exposure during the third trimester on glucose metabolism and sex hormone balance in the offspring. Pregnant mice were intraperitoneally injected with LPS (50 μg/kg) daily from gestational day (GD) 15 to GD17. Glucose tolerance test (GTT) and insulin tolerance test (ITT) were assessed at postnatal day (PND) 60 and PND120. Sex hormones, their receptors, and metabolic enzymes (aromatase) were measured in male offspring at different phases of development (PND14: juvenile; PND35: adolescence; PND60: adulthood; and PND120: middle age). LPS-exposed male offspring exhibited glucose intolerance and insulin resistance by GTT and ITT at middle age, accompanied by an increase in fasting blood glucose and reductions in serum insulin levels and hepatic phosphorylated (p) -AKT/AKT ratio. However, glucose intolerance and insulin resistance were not observed in LPS-exposed female offspring. Maternal LPS exposure upregulated hepatic aromatase proteins and mRNA levels in male offspring at all time points. At adolescence, the testosterone/estradiol ratio (T/E2) was markedly reduced in LPS-exposed male offspring. Moreover, maternal LPS exposure significantly increased hepatic estrogen receptor (ER) α expressions and decreased hepatic androgen receptor (AR) expressions in male offspring. At adulthood, maternal LPS exposure increased serum estradiol levels, decreased serum testosterone levels and elevated hepatic ERβ expressions in male offspring. In conclusion, maternal LPS exposure upregulated aromatase expressions, followed by a reduction in the T/E2 ratio and an alteration in sex hormone receptor activity, which might be involved in the development of glucose metabolism disorders in middle-aged male offspring. This study provides a novel clue and direction to

  18. Identification of the rat liver cytochrome P450 enzymes involved in the metabolism of the calcium channel blocker dipfluzine hydrochloride.

    PubMed

    Guo, Wei; Shi, Xiaowei; Wang, Wei; Zhang, Weili; Li, Junxia

    2014-11-01

    This study aimed to identify the specific cytochrome P450 (CYP450) enzymes involved in the metabolism of dipfluzine hydrochloride using the combination of a chemical inhibition study, a correlation analysis and a panel of recombinant rat CYP450 enzymes. The incubation of Dip with rat liver microsomes yielded four metabolites, which were identified by liquid chromatography-coupled tandem mass spectrometry (LC/MS/MS). The results from the assays involving eight selective inhibitors indicated that CYP3A and CYP2A1 contributed most to the metabolism of Dip, followed by CYP2C11, CYP2E1 and CYP1A2; however, CYP2B1, CYP2C6 and CYP2D1 did not contribute to the formation of the metabolites. The results of the correlation analysis and the assays involving the recombinant CYP450 enzymes further confirmed the above results and concluded that CYP3A2 contributed more than CYP3A1. The results will be valuable in understanding drug-drug interactions when Dip is coadministered with other drugs. Copyright © 2014 Elsevier B.V. All rights reserved.

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

    PubMed

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

    2018-04-18

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

  20. Mechanisms of action for the medium-chain triglyceride ketogenic diet in neurological and metabolic disorders.

    PubMed

    Augustin, Katrin; Khabbush, Aziza; Williams, Sophie; Eaton, Simon; Orford, Michael; Cross, J Helen; Heales, Simon J R; Walker, Matthew C; Williams, Robin S B

    2018-01-01

    High-fat, low-carbohydrate diets, known as ketogenic diets, have been used as a non-pharmacological treatment for refractory epilepsy. A key mechanism of this treatment is thought to be the generation of ketones, which provide brain cells (neurons and astrocytes) with an energy source that is more efficient than glucose, resulting in beneficial downstream metabolic changes, such as increasing adenosine levels, which might have effects on seizure control. However, some studies have challenged the central role of ketones because medium-chain fatty acids, which are part of a commonly used variation of the diet (the medium-chain triglyceride ketogenic diet), have been shown to directly inhibit AMPA receptors (glutamate receptors), and to change cell energetics through mitochondrial biogenesis. Through these mechanisms, medium-chain fatty acids rather than ketones are likely to block seizure onset and raise seizure threshold. The mechanisms underlying the ketogenic diet might also have roles in other disorders, such as preventing neurodegeneration in Alzheimer's disease, the proliferation and spread of cancer, and insulin resistance in type 2 diabetes. Analysing medium-chain fatty acids in future ketogenic diet studies will provide further insights into their importance in modified forms of the diet. Moreover, the results of these studies could facilitate the development of new pharmacological and dietary therapies for epilepsy and other disorders. Copyright © 2018 Elsevier Ltd. All rights reserved.

  1. Central nervous insulin resistance: a promising target in the treatment of metabolic and cognitive disorders?

    PubMed

    Hallschmid, M; Schultes, B

    2009-11-01

    Research on functions and signalling pathways of insulin has traditionally focused on peripheral tissues such as muscle, fat and liver, while the brain was commonly believed to be insensitive to the effects of this hormone secreted by pancreatic beta cells. However, since the discovery some 30 years ago that insulin receptors are ubiquitously found in the central nervous system, an ever-growing research effort has conclusively shown that circulating insulin accesses the brain, which itself does not synthesise insulin, and exerts pivotal functions in central nervous networks. As an adiposity signal reflecting the amount of body fat, insulin provides direct negative feedback to hypothalamic nuclei that control whole-body energy and glucose homeostasis. Moreover, insulin affects distinct cognitive processes, e.g. by triggering the formation of psychological memory contents. Accordingly, metabolic and cognitive disorders such as obesity, type 2 diabetes mellitus and Alzheimer's disease are associated with resistance of central nervous structures to the effects of insulin, which may derive from genetic polymorphisms as well as from long-term exposure to excess amounts of circulating insulin due to peripheral insulin resistance. Thus, overcoming central nervous insulin resistance, e.g. by pharmacological interventions, appears to be an attractive strategy in the treatment and prevention of these disorders. Enhancement of central nervous insulin signalling by administration of intranasal insulin, insulin analogues and insulin sensitisers in basic research approaches has yielded encouraging results that bode well for the successful translation of these effects into future clinical practice.

  2. The effect of different amounts of calcium intake on bone metabolism and arterial calcification in ovariectomized rats.

    PubMed

    Agata, Umon; Park, Jong-Hoon; Hattori, Satoshi; Iimura, Yuki; Ezawa, Ikuko; Akimoto, Takayuki; Omi, Naomi

    2013-01-01

    Low calcium (Ca) intake is the one of risk factors for both bone loss and medial elastocalcinosis in an estrogen deficiency state. To examine the effect of different amounts of Ca intake on the relationship between bone mass alteration and medial elastocalcinosis, 6-wk-old female SD rats were randomized into ovariectomized (OVX) control or OVX treated with vitamin D(3) plus nicotine injection (VDN) groups. The OVX treated with VDN group was then divided into 5 groups depending on the different Ca content in their diet, 0.01%, 0.1%, 0.6%, 1.2%, and 2.4% Ca intakes. After 8 wk of experimentation, the low Ca intake groups of 0.01% and 0.1% showed a low bone mineral density (BMD) and bone properties significantly different from those of the other groups, whereas the high Ca intake groups of 1.2% and 2.4% showed no difference compared with the OVX control. Only in the 0.01% Ca intake group, a significantly higher Ca content in the thoracic artery was found compared with that of the OVX control. Arterial tissues of the 0.01% Ca intake group showed an increase of bone-specific alkaline phosphatase (BAP) activity, a marker of bone mineralization, associated with arterial Ca content. However, the high Ca intake did not affect arterial Ca content nor arterial BAP activity. These results suggested that a low Ca intake during periods of rapid bone loss caused by estrogen deficiency might be one possible cause for the complication of both bone loss and medial elastocalcinosis.

  3. Effect of intermittent exposure to 3% CO2 on respiration, acid-base balance, and calcium-phosphorus metabolism.

    PubMed

    Schaefer, K E; Carey, C R; Dougherty, J H; Morgan, C; Messier, A A

    1979-01-01

    One subject was exposed for six days to increasing levels of CO2, rising at a constant rate from 0.03 to 3.0% CO2 within a 15-h period followed by 9 h of air breathing. To assess acid-base parameters, arterialized capillary blood was taken from a finger twice daily (at 8 a.m. and 11 p.m.) at times corresponding to the beginning and end of the intermittent exposure to CO2. Venous blood samples were obtained on alternate days at the same times. Urine specimens were collected twice daily. The subject was on a liquid diet. Resting respiratory minute volume (VE), oxygen consumption (VO2), carbon dioxide excretion (VCO2), alveolar carbon dioxide and oxygen tension (PACO2) and PAO2) were measured twice daily. PACO2 and PAO2 were also determined at the end of breath-holding twice daily; CO2 tolerance tests and lung function tests were also carried out. In contrast to the effects of chronic exposure to 3% CO2, the CO2 tolerance tests showed an increased sensitivity (increase of slope) and breath-holding PACO2 did not change, indicating that acclimatization to CO2 did not develop. The ventilatory response to CO2 was not sufficient to prevent CO2 accumulation in the body; this accumulation was eliminated during the nightly air-breathing periods on the fourth and fifth days, indicated by higher values of PaCO2 and PACO2. The known renal response to hypercapnia, consisting of an increased excretion of titratable acidity, ammonia, and hydrogen ion excretion, occurred but was interrupted after the first day and was triggered again on the fourth and fith days when accumulated CO2 was released from body CO2 stores. The second renal response was associated with a marked calcium excretion, which suggests that bone CO2 stores were involved.

  4. Radiological study of the effect of low calcium diet on the mineral metabolism of bone tissue. With reference to mineralization in callus (in Japanese)

    SciTech Connect

    Nakamura, K.

    1972-01-01

    Deficiency of available food material due either to poor diet or to malabsorption may adversely affect the skeleton. To study the affection, DDN mice were fed low calcium diet to induce low calcium state corresponding to malabsorption of calcium from the intestine. The femur was fractured manually. Then, calcium deposition in the callus was observed by microradiography and tracer technics with /sup 47/Ca. Increase of the body weight in mice fed low calcium diet was much slower than in the control. The affection of the low calcium diet on bone tissue appeared as a decrease of precipitation of calcium salt.more » This tendency was also observed in callus, Tracer study with /sup 47/Ca was performed in mice fed the low calcium diet for 24 days. Incorporation activity of calcium was generally high in each organ except the kidney. Callus in the site of the fracture in mice fed a low calcium diet was formed to the same degree as the control, although the amount of precipitated calcium in it was significantly poorer. In summary, insufficient mineralization in relation to osteogenesis occurred when the supply of the requisite electrolytes was insufficient or inappropriate. On the other hand, the uptake rate of calcinm in the callus was elevated even in the calcium deficient state. (auth)« less

  5. The association of posttraumatic stress disorder and metabolic syndrome: a study of increased health risk in veterans.

    PubMed

    Heppner, Pia S; Crawford, Eric F; Haji, Uzair A; Afari, Niloofar; Hauger, Richard L; Dashevsky, Boris A; Horn, Paul S; Nunnink, Sarah E; Baker, Dewleen G

    2009-01-09

    There is accumulating evidence for a link between trauma exposure, posttraumatic stress disorder (PTSD) and diminished health status. To assess PTSD-related biological burden, we measured biological factors that comprise metabolic syndrome, an important established predictor of morbidity and mortality, as a correlate of long-term health risk in PTSD. We analyzed clinical data from 253 male and female veterans, corresponding to five factors linked to metabolic syndrome (systolic and diastolic blood pressure, waist-to-hip ratio and fasting measures of high-density lipoprotein (HDL) cholesterol, serum triglycerides and plasma glucose concentration). Clinical cut-offs were defined for each biological parameter based on recommendations from the World Health Organization and the National Cholesterol Education Program. Controlling for relevant variables including sociodemographic variables, alcohol/substance/nicotine use and depression, we examined the impact of PTSD on metabolic syndrome using a logistic regression model. Two-fifths (40%) of the sample met criteria for metabolic syndrome. Of those with PTSD (n = 139), 43% met criteria for metabolic syndrome. The model predicted metabolic syndrome well (-2 log likelihood = 316.650, chi-squared = 23.731, p = 0.005). Veterans with higher severity of PTSD were more likely to meet diagnostic criteria for metabolic syndrome (Wald = 4.76, p = 0.03). These findings provide preliminary evidence linking higher severity of PTSD with risk factors for diminished health and increased morbidity, as represented by metabolic syndrome.

  6. The association of posttraumatic stress disorder and metabolic syndrome: a study of increased health risk in veterans

    PubMed Central

    Heppner, Pia S; Crawford, Eric F; Haji, Uzair A; Afari, Niloofar; Hauger, Richard L; Dashevsky, Boris A; Horn, Paul S; Nunnink, Sarah E; Baker, Dewleen G

    2009-01-01

    Background There is accumulating evidence for a link between trauma exposure, posttraumatic stress disorder (PTSD) and diminished health status. To assess PTSD-related biological burden, we measured biological factors that comprise metabolic syndrome, an important established predictor of morbidity and mortality, as a correlate of long-term health risk in PTSD. Methods We analyzed clinical data from 253 male and female veterans, corresponding to five factors linked to metabolic syndrome (systolic and diastolic blood pressure, waist-to-hip ratio and fasting measures of high-density lipoprotein (HDL) cholesterol, serum triglycerides and plasma glucose concentration). Clinical cut-offs were defined for each biological parameter based on recommendations from the World Health Organization and the National Cholesterol Education Program. Controlling for relevant variables including sociodemographic variables, alcohol/substance/nicotine use and depression, we examined the impact of PTSD on metabolic syndrome using a logistic regression model. Results Two-fifths (40%) of the sample met criteria for metabolic syndrome. Of those with PTSD (n = 139), 43% met criteria for metabolic syndrome. The model predicted metabolic syndrome well (-2 log likelihood = 316.650, chi-squared = 23.731, p = 0.005). Veterans with higher severity of PTSD were more likely to meet diagnostic criteria for metabolic syndrome (Wald = 4.76, p = 0.03). Conclusion These findings provide preliminary evidence linking higher severity of PTSD with risk factors for diminished health and increased morbidity, as represented by metabolic syndrome. PMID:19134183

  7. Regional cerebral glucose metabolism differentiates danger- and non-danger-based traumas in post-traumatic stress disorder

    PubMed Central

    Litz, Brett T.; Resick, Patricia A.; Woolsey, Mary D.; Dondanville, Katherine A.; Young-McCaughan, Stacey; Borah, Adam M.; Borah, Elisa V.; Peterson, Alan L.; Fox, Peter T.

    2016-01-01

    Post-traumatic stress disorder (PTSD) is presumably the result of life threats and conditioned fear. However, the neurobiology of fear fails to explain the impact of traumas that do not entail threats. Neuronal function, assessed as glucose metabolism with 18fluoro-deoxyglucose positron emission tomography, was contrasted in active duty, treatment-seeking US Army Soldiers with PTSD endorsing either danger- (n = 19) or non-danger-based (n = 26) traumas, and was compared with soldiers without PTSD (Combat Controls, n = 26) and Civilian Controls (n = 24). Prior meta-analyses of regions associated with fear or trauma script imagery in PTSD were used to compare glucose metabolism across groups. Danger-based traumas were associated with higher metabolism in the right amygdala than the control groups, while non-danger-based traumas associated with heightened precuneus metabolism relative to the danger group. In the danger group, PTSD severity was associated with higher metabolism in precuneus and dorsal anterior cingulate and lower metabolism in left amygdala (R2 = 0.61). In the non-danger group, PTSD symptom severity was associated with higher precuneus metabolism and lower right amygdala metabolism (R2 = 0.64). These findings suggest a biological basis to consider subtyping PTSD according to the nature of the traumatic context. PMID:26373348

  8. [Metabolic Syndrome and Bipolar Affective Disorder: A Review of the Literature].

    PubMed

    Jaramillo, Carlos López; Mejía, Adelaida Castaño; Velásquez, Alicia Henao; Restrepo Palacio, Tomás Felipe; Zuluaga, Julieta Osorio

    2013-09-01

    Bipolar disorder (BD) is a chronic psychiatric disorder that is found within the first ten causes of disability and premature mortality. The metabolic syndrome (MS) is a group of risk factors (RF) that predispose to cardiovascular disease (CV), diabetes and early mortality. Both diseases generate high costs to the health system. Major studies have shown that MS has a higher prevalence in patients with mental disorders compared to the general population. The incidence of MS in BD is multifactorial, and due to iatrogenic, genetic, economic, psychological, and behavioral causes related to the health system. The most common RF found is these patients was an increased abdominal circumference, and it was found that the risk of suffering this disease was greater in women and Hispanic patients. As regards the increase in RF to develop a CV in patients with BD, there have been several explanations based on the risky behavior of patients with mental illness, included tobacco abuse, physical inactivity and high calorie diets. An additional explanation described in literature is the view of BD as a multisystemic inflammatory illness, supported by the explanation that inflammation is a crucial element in atherosclerosis, endothelial dysfunction, platelet rupture, and thrombosis. The pathophysiology of MS and BD include factors such as adrenal, thyroid and sympathetic nervous system dysfunction, as well as poor lifestyle and medication common in these patients. This article attempts to give the reader an overall view of the information published in literature to date, as regards the association between BD and MS. Copyright © 2013 Asociación Colombiana de Psiquiatría. Publicado por Elsevier España. All rights reserved.

  9. Metformin for weight loss and metabolic control in overweight outpatients with schizophrenia and schizoaffective disorder.

    PubMed

    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.

  10. Resveratrol restores the circadian rhythmic disorder of lipid metabolism induced by high-fat diet in mice.

    PubMed

    Sun, Linjie; Wang, Yan; Song, Yu; Cheng, Xiang-Rong; Xia, Shufang; Rahman, Md Ramim Tanver; Shi, Yonghui; Le, Guowei

    2015-02-27

    Circadian rhythmic disorders induced by high-fat diet are associated with metabolic diseases. Resveratrol could improve metabolic disorder, but few reports focused on its effects on circadian rhythm disorders in a variety of studies. The aim of the present study was to analyze the potential effects of resveratrol on high-fat diet-induced disorders about the rhythmic expression of clock genes and clock-controlled lipid metabolism. Male C57BL/6 mice were divided into three groups: a standard diet control group (CON), a high-fat diet (HFD) group and HFD supplemented with 0.1% (w/w) resveratrol (RES). The body weight, fasting blood glucose and insulin, plasma lipids and leptin, whole body metabolic status and the expression of clock genes and clock-controlled lipogenic genes were analyzed at four different time points throughout a 24-h cycle (8:00, 14:00, 20:00, 2:00). Resveratrol, being associated with rhythmic restoration of fasting blood glucose and plasma insulin, significantly decreased the body weight in HFD mice after 11 weeks of feeding, as well as ameliorated the rhythmities of plasma leptin, lipid profiles and whole body metabolic status (respiratory exchange ratio, locomotor activity, and heat production). Meanwhile, resveratrol modified the rhythmic expression of clock genes (Clock, Bmal1 and Per2) and clock-controlled lipid metabolism related genes (Sirt1, Pparα, Srebp-1c, Acc1 and Fas). The response pattern of mRNA expression for Acc1 was similar to the plasma triglyceride. All these results indicated that resveratrol reduced lipogenesis and ultimately normalized rhythmic expression of plasma lipids, possibly via its action on clock machinery. Copyright © 2015 Elsevier Inc. All rights reserved.

  11. Calcium Kinetics During Space Flight

    NASA Technical Reports Server (NTRS)

    Smith, Scott M.; Wastney, Meryl E.; OBrien, Kimberly O.; Lane, Helen W.

    1999-01-01

    Bone loss is one of the most detrimental effects of space flight, threatening to limit the duration of human space missions. The ability to understand and counteract this loss will be critical for crew health and safety during and after extended-duration missions. The hypotheses to be tested in this project are that space flight alters calcium homeostasis and bone mineral metabolism, and that calcium homeostasis and bone mineral metabolism will return to baseline within days to weeks of return to Earth. These hypotheses will be evidenced by elevated rates of bone mineral resorption and decreased bone mineral deposition, decreased absorption of dietary calcium, altered calcitropic endocrine profiles, elevated excretion of calcium in urine and feces, and elevated excretion of markers of bone resorption. The second hypothesis will be evidenced by return of indices of calcium homeostasis and bone metabolism to preflight levels within days to weeks of return to Earth. Studies will be conducted on International Space Station astronauts before, during, and after extended-duration flights. Measurements of calcium kinetics, bone mass, and endocrine/biochemical markers of bone and calcium homeostasis will be conducted. Kinetic studies utilizing dual isotope tracer kinetic studies and mathematical modeling techniques will allow for determination of bone calcium deposition, bone calcium resorption, dietary calcium absorption and calcium excretion (both urinary and endogenous fecal excretion). These studies will build upon preliminary work conducted on the Russian Mir space station. The results from this project will be critical for clarifying how microgravity affects bone and calcium homeostasis, and will provide an important control point for assessment of countermeasure efficacy. These results are expected to aid in developing countermeasures for bone loss, both for space crews and for individuals on Earth who have metabolic bone diseases.

  12. Effect of a high dose of simvastatin on muscle mitochondrial metabolism and calcium signaling in healthy volunteers

    SciTech Connect

    Galtier, F., E-mail: f-galtier@chu-montpellier.fr; INSERM, CIC 1001, 80 Avenue Augustin Fliche, 34295 Montpellier Cedex 5; CPID, Faculté de Pharmacie, 15 Av. Charles Flahault, BP 14491, 34093 Montpellier Cedex 5, Montpellier

    Statin use may be limited by muscle side effects. Although incompletely understood to date, their pathophysiology may involve oxidative stress and impairments of mitochondrial function and of muscle Ca{sup 2+} homeostasis. In order to simultaneously assess these mechanisms, 24 male healthy volunteers were randomized to receive either simvastatin for 80 mg daily or placebo for 8 weeks. Blood and urine samples and a stress test were performed at baseline and at follow-up, and mitochondrial respiration and Ca{sup 2+} spark properties were evaluated on a muscle biopsy 4 days before the second stress test. Simvastatin-treated subjects were separated according to theirmore » median creatine kinase (CK) increase. Simvastatin treatment induced a significant elevation of aspartate amino transferase (3.38 ± 5.68 vs − 1.15 ± 4.32 UI/L, P < 0.001) and CK (− 24.3 ± 99.1 ± 189.3vs 48.3 UI/L, P = 0.01) and a trend to an elevation of isoprostanes (193 ± 408 vs12 ± 53 pmol/mmol creatinine, P = 0.09) with no global change in mitochondrial respiration, lactate/pyruvate ratio or Ca{sup 2+} sparks. However, among statin-treated subjects, those with the highest CK increase displayed a significantly lower Vmax rotenone succinate and an increase in Ca{sup 2+} spark amplitude vs both subjects with the lowest CK increase and placebo-treated subjects. Moreover, Ca{sup 2+} spark amplitude was positively correlated with treatment-induced CK increase in the whole group (r = 0.71, P = 0.0045). In conclusion, this study further supports that statin induced muscular toxicity may be related to alterations in mitochondrial respiration and muscle calcium homeostasis independently of underlying disease or concomitant medication. -- Highlights: ► Statin use may be limited by side effects, particularly myopathy. ► Statins might impair mitochondrial function and muscle Ca2+ signaling in muscle. ► This was tested among healthy volunteers receiving simvastatin 80 mg daily for 8 weeks.

  13. Additive effects of fibroblast growth factor 23 neutralization and dietary phytase on chick calcium and phosphorus metabolism.

    PubMed

    Ren, Z Z; Bütz, D E; Wahhab, A N; Piepenburg, A J; Cook, M E

    2017-05-01

    Phytase hydrolyzes phytate rendering phosphorus available for intestinal absorption, while systemic neutralization of fibroblast growth factor 23 (FGF-23), using anti-FGF-23 antibody, has been shown to increase phosphate retention. Hence, neutralization of FGF-23 should be additive with phytase in reducing dietary non-phytate phosphorus (nPP) needs in chickens fed plant-based diets rich in phytic acid. This study was designed to test the additive effects of maternally derived anti-FGF-23 antibody and dietary phytase on the performance of chicks fed a low nPP diet from one to 14 d. Single Comb White Leghorn laying hens were vaccinated with either an adjuvant control or a synthetic FGF-23 peptide (GMNPPPYS). Chicks from vaccinated hens with control or anti-FGF-23 maternal antibodies were fed either a diet containing 0.2% nPP and 0.9% calcium with or without 500 unit phytase per kg of diet (2 × 2 factorial with main effects of antibody type and phytase addition, n = 15 pens of chicks/treatment). A significant interaction between dietary phytase and maternally derived anti-FGF-23 antibody on growth and feed efficiency was observed (P ≤ 0.05), in which chicks receiving either phytase or maternally derived anti-FGF-23 antibody had improved body weight gain (21 or 15%, respectively) and feed efficiency (16 or 18%, respectively) as compared to chicks with control antibody and not fed phytase. Both phytase and maternally derived anti-FGF-23 antibody independently increased (P ≤ 0.05) plasma phosphate (11 and 11%, respectively) and percent tibiotarsus ash (13 and 11%, respectively). Significant main effects and the lack of an interaction supported an additive effect of phytase and anti-FGF-23 antibody on plasma phosphate and percent tibiotarsus ash. Feeding phytase to chicks fed 0.2% nPP increased plasma FGF-23 levels by 22% (P ≤ 0.05); however, no effects of anti-FGF-23 antibody on plasma FGF-23 levels were observed. In conclusion, dietary phytase and presence of

  14. Diagnosis and assessment of skeletal related disease using calcium 41

    DOEpatents

    Hillegonds, Darren J [Oakland, CA; Vogel, John S [San Jose, CA; Fitzgerald, Robert L [Encinitas, CA; Deftos, Leonard J [Del Mar, CA; Herold, David [Del Mar, CA; Burton, Douglas W [San Diego, CA

    2012-05-15

    A method of determining calcium metabolism in a patient comprises the steps of administering radioactive calcium isotope .sup.41Ca to the patient, allowing a period of time to elapse sufficient for dissemination and reaction of the radioactive calcium isotope .sup.41Ca by the patient, obtaining a sample of the radioactive calcium isotope .sup.41Ca from the patient, isolating the calcium content of the sample in a form suitable for precise measurement of isotopic calcium concentrations, and measuring the calcium content to determine parameters of calcium metabolism in the patient.

  15. Diagnosis and assessment of skeletal related disease using calcium 41

    DOEpatents

    Hillegonds, Darren J.; Vogel, John S.; Fitzgerald, Robert L.; Deftos, Leonard J.; Herold, David; Burton, Douglas W.

    2013-03-05

    A method of determining calcium metabolism in a patient comprises the steps of administering radioactive calcium isotope .sup.41Ca to the patient, allowing a period of time to elapse sufficient for dissemination and reaction of the radioactive calcium isotope .sup.41Ca by the patient, obtaining a sample of the radioactive calcium isotope .sup.41Ca from the patient, isolating the calcium content of the sample in a form suitable for precise measurement of isotopic calcium concentrations, and measuring the calcium content to determine parameters of calcium metabolism in the patient.

  16. Metabolic syndrome and adverse clinical outcomes in patients with bipolar disorder.

    PubMed

    Bai, Ya-Mei; Li, Cheng-Ta; Tsai, Shih-Jen; Tu, Pei-Chi; Chen, Mu-Hong; Su, Tung-Ping

    2016-12-15

    Metabolic syndrome (MetS) is highly prevalent among patients with bipolar disorder. MetS may cause complications in the brain, but studies investigating MetS-associated clinical psychiatric outcomes remain scant. We enrolled clinically stable outpatients with bipolar disorder aged 18-65 years and performed anthropometric and fasting biochemical assessments to investigate MetS prevalence. We then performed clinical assessments by using the Young Mania Rating Scale for manic symptoms, the Montgomery-Åsberg Depression Rating Scale for depressive symptoms, the Positive and Negative Symptom Scale for psychotic symptoms, the Involuntary Movement Scale for tardive dyskinesia, the Barnes Akathisia Rating Scale for akathisia, the Udvalg for Kliniske Undersogelser for general side effects, the Schedule for Assessment of Insight for insight, the Global Assessment of Functioning scale for global functioning, and the Wisconsin Card Sorting Test (WCST) for cognitive executive function. In total, 143 patients were enrolled and had a MetS prevalence of 29.4%. The patients treated with atypical antipsychotics plus mood stabilizers (36.3%) and atypical antipsychotics alone (36.0%) had a significantly higher prevalence of MetS than did those treated with mood stabilizers alone (10.5%; p = 0.012). According to multivariate regression analyses adjusted for age, sex, smoking status, bipolar disorder subtype (I or II), pharmacological treatment duration, and psychiatric medication, compared with patients without MetS, those with MetS had significantly more previous hospitalizations (p = 0.036), severer tardive dyskinesia (p = 0.030), poorer insight (p = 0.036), poorer global function (p = 0.046), and more impaired executive function (conceptual level response on the WCST; p = 0.042). Our results indicated that patients with comorbid bipolar disorder and MetS have more adverse clinical outcomes than those without, with more hospitalizations, severer tardive

  17. Vitamin D status in growing dairy goats and sheep: Influence of ultraviolet B radiation on bone metabolism and calcium homeostasis.

    PubMed

    Nemeth, M V; Wilkens, M R; Liesegang, A

    2017-10-01

    The aim of this study was to investigate how controlled UVB irradiation in combination with reduced nutritional vitamin D (vitD) supply affects vitD status and Ca metabolism of growing goats and sheep. The hypothesis was that, like dairy cows, goats and sheep are able to compensate for the missing nutritional supply of vitD through endogenous production in the skin, with the consequence of a high vitD status and a balanced Ca homeostasis. Sixteen lambs and 14 goat kids aged 3 and a half months were housed in an UVB free environment and fed hay and a vitD-free concentrate over a period of 13 wk. One group of each species was exposed to UVB lamps daily during individual feeding; the other groups served as controls. Serum, urine, and feces samples were taken at the start and at a monthly interval. Serum was analyzed for vitD metabolites, bone markers, growth hormone, insulin-like growth factor I, Ca, and P. Apparent digestibility and urinary excretion of Ca and P were determined. The left metatarsus was analyzed by peripheral quantitative computer tomography for bone mineral density before starting and at the end of the trial. In wk 13, all animals were slaughtered and samples of skin, rumen, duodenum, kidney, and bone (metatarsus) were collected. Content of sterols of vitD synthesis in the skin, Ca flux rates in rumen and duodenum, expression of vitD receptor in duodenum and kidney, renal and intestinal gene expression of Ca transport proteins, and renal enzymes related to vitD metabolism were determined. The UVB exposure led to lower 7-dehydrocholesterol content in the skin and a better vitD status (higher serum 25-hydroxyvitamin D), but no signs of vitD deficiency were seen in the control groups and no effect of irradiation was detected in the analyzed parameters of Ca homeostasis. Differences between the 2 species were detected: lambs had a higher increase of bone mineral density, lower values of bone markers, growth hormone, and insulin-like growth factor I in

  18. Comparative effects of denosumab or bisphosphonate treatment on bone mineral density and calcium metabolism in postmenopausal women.

    PubMed

    Augoulea, A; Tsakonas, E; Triantafyllopoulos, I; Rizos, D; Armeni, E; Tsoltos, N; Tournis, S; Deligeoroglou, E; Antoniou, A; Lambrinoudaki, I

    2017-03-01

    To clarify potential differences between denosumab (DNS) and bisphosphonates (BIS) in terms of bone density and bone metabolism, in a sample of postmenopausal women. A total of 113 postmenopausal women aged 53-66 years were treated with either DNS or BIS for 12 months. Bone densitometry and laboratory tests were compared between baseline and follow-up. Femoral neck BMD increased in both treatment-arms (FN-BMD, DNS: 0.69±0.07 g/cm 2 to 0.75±0.09 g/cm 2 ; BIS: 0.69±0.06 g/cm 2 to 0.71±0.07 g/cm 2 ; p≤0.001 in both cases). Lumbar spine BMD (LS-BMD) increased significantly only in the DNS-group (0.83±0.14 g/cm 2 to 0.89±0.14 g/cm 2 , p=0.0001). Only women under treatment with DNS had a significant increase in serum parathyroid hormone (PTH: 44.87±17.54 pg/mL to 53.27±15.77 pg/mL, p=0.04), independently of baseline vitamin D levels. DNS-administration resulted in higher increase from baseline in FN-BMD compared to BIS (DNS vs BIS: 8.7%±8.5 vs 3.8%±7.3, p=0.004). Finally, baseline 25OH vitamin D levels did not determine the extent of PTH-increase following administration of DNS- or BIS-treatment. Both treatments increased BMD, however, the effect of DNS on FN-BMD was superior compared to that of BIS. DNS-treatment increased serum PTH. Baseline 25OH vitamin D levels did not predict the extent of PTH increase at follow-up.

  19. Brain-derived neurotrophic factor, impaired glucose metabolism, and bipolar disorder course.

    PubMed

    Mansur, Rodrigo B; Santos, Camila M; Rizzo, Lucas B; Asevedo, Elson; Cunha, Graccielle R; Noto, Mariane N; Pedrini, Mariana; Zeni-Graiff, Maiara; Cordeiro, Quirino; Vinberg, Maj; Kapczinski, Flavio; McIntyre, Roger S; Brietzke, Elisa

    2016-06-01

    The neurotrophin brain-derived neurotrophic factor (BDNF) has been proposed as a potential biomarker in bipolar disorder (BD). However, current evidence is limited and results have been highly heterogeneous. This study aimed to assess the moderating effect of impaired glucose metabolism (IGM) on plasma levels of BDNF in individuals with BD, and on the relationship between BDNF and variables of illness course. We measured and compared the plasma levels of BDNF in individuals with BD (n=57) and healthy controls (n=26). IGM was operationalized as pre-diabetes or type 2 diabetes mellitus. Information related to current and past psychiatric/medical history, as well as prescription of pharmacological treatments was also captured. Individuals with BD had lower levels of BDNF, relative to healthy controls, after adjustment for age, gender, current medications, smoking, alcohol use, and IGM (P=.046). There was no effect of IGM (P=.860) and no interaction between BD diagnosis and IGM (P=.893). Peripheral BDNF levels were positively correlated with lifetime depressive episodes (P<.001), psychiatric hospitalizations (P=.001) and suicide attempts (P=.021). IGM moderated the association between BDNF and the number of previous mood episodes (P<.001), wherein there was a positive correlation in euglycemic participants and a negative correlation in individuals with IGM. BD is independently associated with lower levels of BDNF; IGM may modify the relationship between BDNF and BD course, suggesting an interactive effect of BDNF with metabolic status on illness progression. © 2016 John Wiley & Sons A/S Published by John Wiley & Sons Ltd.

  20. Association between Glucose Metabolism and Sleep-disordered Breathing during REM Sleep.

    PubMed

    Chami, Hassan A; Gottlieb, Daniel J; Redline, Susan; Punjabi, Naresh M

    2015-11-01

    Sleep-disordered breathing (SDB) has been associated with impaired glucose metabolism. It is possible that the association between SDB and glucose metabolism is distinct for non-REM versus REM sleep because of differences in sleep-state-dependent sympathetic activation and/or degree of hypoxemia. To characterize the association between REM-related SDB, glucose intolerance, and insulin resistance in a community-based sample. A cross-sectional analysis that included 3,310 participants from the Sleep Heart Health Study was undertaken (53% female; mean age, 66.1 yr). Full montage home-polysomnography and fasting glucose were available on all participants. SDB severity during REM and non-REM sleep was quantified using the apnea-hypopnea index in REM (AHIREM) and non-REM sleep (AHINREM), respectively. Fasting and 2-hour post-challenge glucose levels were assessed during a glucose tolerance test (n = 2,264). The homeostatic model assessment index for insulin resistance (HOMA-IR) was calculated (n = 1,543). Linear regression was used to assess the associations of AHIREM and AHINREM with fasting and post-prandial glucose levels and HOMA-IR. AHIREM and AHINREM were associated with fasting glycemia, post-prandial glucose levels, and HOMA-IR in models that adjusted for age, sex, race, and site. However, with additional adjustment for body mass index, waist circumference, and sleep duration, AHIREM was only associated with HOMA-IR (β = 0.04; 95% CI, 0.1-0.07; P = 0.01), whereas AHINREM was only associated with fasting (β = 0.93; 95% CI, 0.14-1.72; P = 0.02) and post-prandial glucose levels (β = 3.0; 95% CI, 0.5-5.5; P = 0.02). AHIREM is associated with insulin resistance but not with fasting glycemia or glucose intolerance.

  1. The Effects of an Exercise Program on Anxiety Levels and Metabolic Functions in Patients With Anxiety Disorders.

    PubMed

    Ma, Wei-Fen; Wu, Po-Lun; Su, Chia-Hsien; Yang, Tzu-Ching

    2017-05-01

    The purpose of this study was to evaluate the effects of a home-based (HB) exercise program on anxiety levels and metabolic functions in patients with anxiety disorders in Taiwan. Purposive sampling was used to recruit 86 participants for this randomized, experimental study. Participants were asked to complete a pretest before the 3-month exercise program, a posttest at 1 week, and a follow-up test at 3 months after the exercise program. Study measures included four Self-Report Scales and biophysical assessments to collect and assess personal data, lifestyle behaviors, anxiety levels, and metabolic control functions. Of the 86 study participants, 83 completed the posttest and the 3-month follow-up test, including 41 in the experimental group and 42 in the control group. Participants in the experimental group showed significant improvements in body mass index, high-density lipoprotein cholesterol levels, and the level of moderate exercise after the program relative to the control group, as analyzed by generalized estimating equations mixed-model repeated measures. State and trait anxiety levels were also significantly improved from pretest to follow-up test in the experimental group. Finally, the prevalence of metabolic syndrome declined for participants in the experimental group. The HB exercise program produced positive effects on the metabolic indicators and anxiety levels of Taiwanese adults with anxiety disorders. Health providers should consider using similar HB exercise programs to help improve the mental and physical health of patients with anxiety disorders in their communities.

  2. The degree of cycle irregularity correlates with the grade of endocrine and metabolic disorders in PCOS patients.

    PubMed

    Strowitzki, Thomas; Capp, Edison; von Eye Corleta, Helena

    2010-04-01

    PCOS (polycystic ovarian syndrome) is a clinically heterogeneous endocrine disorder which affects up to 4-10% of women of reproductive age. A standardized definition is still difficult because of a huge variety of different phenotypes. The aim of this study was to evaluate possible correlations between the degree of cycle irregularity and the grade of endocrine and metabolic abnormalities. A cross-sectional study was carried out. Hyperandrogenic and/or hirsute women with regular menstrual cycles and polycystic ovaries on ultrasound (PCOS eumenorr, n=45), PCOS patients with oligomenorrhea (PCOS oligo, n=42) and PCOS patients with amenorrhea (PCOS amenorr, n=31) were recruited from the Department of Gynecological Endocrinology and Reproductive Medicine of the Women's University Hospital Heidelberg (Heidelberg, Germany). Normocyclic patients demonstrated significantly better metabolic parameters (BMI, fasting insulin, HOMA-IR) than patients with oligo/amenorrhea. Hormonal parameters (LH, FSH, FAI and testosterone) were significantly different between patients with different menstrual patterns and patients with regular cycles. Determining the degree of cycle irregularity as a simple clinical parameter might be a valuable instrument to estimate the degree of metabolic and endocrine disorders. Emphasis should be given to those parameters as a first step to characterize PCOS patients with a risk of endocrine and metabolic disorders leading to consequent detailed examination. Copyright (c) 2010 Elsevier Ireland Ltd. All rights reserved.

  3. Systemic inhibition of Janus kinase induces browning of white adipose tissue and ameliorates obesity-related metabolic disorders.

    PubMed

    Qurania, Kikid Rucira; Ikeda, Koji; Wardhana, Donytra Arby; Barinda, Agian Jeffilano; Nugroho, Dhite Bayu; Kuribayashi, Yuko; Rahardini, Elda Putri; Rinastiti, Pranindya; Ryanto, Gusty Rizky Teguh; Yagi, Keiko; Hirata, Ken-Ichi; Emoto, Noriaki

    2018-07-07

    Browning of white adipose tissue is a promising strategy to tackle obesity. Recently, Janus kinase (JAK) inhibition was shown to induce white-to-brown metabolic conversion of adipocytes in vitro; however effects of JAK inhibition on browning and systemic metabolic health in vivo remain to be elucidated. Here, we report that systemic administration of JAK inhibitor (JAKi) ameliorated obesity-related metabolic disorders. Administration of JAKi in mice fed a high-fat diet increased UCP-1 and PRDM16 expression in white adipose tissue, indicating the browning of white adipocyte. Food intake was increased in JAKi-treated mice, while the body weight and adiposity was similar between the JAKi- and vehicle-treated mice. In consistent with the browning, thermogenic capacity was enhanced in mice treated with JAKi. Chronic inflammation in white adipose tissue was not ameliorated by JAKi-treatment. Nevertheless, insulin sensitivity was well preserved in JAKi-treated mice comparing with that in vehicle-treated mice. Serum levels of triglyceride and free fatty acid were significantly reduced by JAKi-treatment, which is accompanied by ameliorated hepatosteatosis. Our data demonstrate that systemic administration of JAKi has beneficial effects in preserving metabolic health, and thus inhibition of JAK signaling has therapeutic potential for the treatment of obesity and its-related metabolic disorders. Copyright © 2018 Elsevier Inc. All rights reserved.

  4. Nutritional and Metabolic Biomarkers in Autism Spectrum Disorders: An Exploratory Study

    PubMed Central

    Esparham, Anna E.; Smith, Teri; Belmont, John M.; Haden, Michael; Wagner, Leigh E.; Evans, Randall G.; Drisko, Jeanne A.

    2015-01-01

    Context Autism spectrum disorder (ASD) is currently on the rise, now affecting approximately 1 in 68 children in the United States according to a 2010 surveillance summary from the Centers for Disease Control and Prevention (CDC). This figure is an estimated increase of 78% from the figure in 2002. The CDC suggests that more investigation is needed to understand this astounding increase in autism in such a short period. Objective The aim of this pilot study was to determine whether a group of children with ASD exhibited similar variations in a broad array of potential correlates, including medical histories, symptoms, genetics, and multiple nutritional and metabolic biomarkers. Design This study was a retrospective, descriptive chart review. Setting The study took place at the University of Kansas Medical Center (KUMC). Participants Participants were 7 children with ASD who had sought treatment at the Integrative Medicine Clinic at the medical center. Results A majority of the children exhibited an elevated copper:zinc ratio and abnormal vitamin D levels. Children also demonstrated abnormal levels of the essential fatty acids: (1) α-linolenic acid (ALA)— C13:3W3, and (2) linoleic acid (LA)—C18:2W6; high levels of docosahexaenoic acid (DHA); and an elevated ω-6:ω-3 ratio. Three of 7 children demonstrated abnormal manganese levels. Children did not demonstrate elevated urine pyruvate or lactate but did have abnormal detoxification markers. Three of 7 patients demonstrated abnormalities in citric acid metabolites, bacterial metabolism, and fatty acid oxidation markers. A majority demonstrated elevated serum immunoglobulin G (IgG) antibodies to casein, egg whites, egg yolks, and peanuts. A majority had absent glutathione S-transferase (GSTM) at the 1p13.3 location, and 3 of 7 children were heterozygous for the glutathione S-transferase I105V (GSTP1). A majority also exhibited genetic polymorphism of the mitochondrial gene superoxide dismutase A16V (SOD2

  5. Nutritional and Metabolic Biomarkers in Autism Spectrum Disorders: An Exploratory Study.

    PubMed

    Esparham, Anna E; Smith, Teri; Belmont, John M; Haden, Michael; Wagner, Leigh E; Evans, Randall G; Drisko, Jeanne A

    2015-04-01

    Autism spectrum disorder (ASD) is currently on the rise, now affecting approximately 1 in 68 children in the United States according to a 2010 surveillance summary from the Centers for Disease Control and Prevention (CDC). This figure is an estimated increase of 78% from the figure in 2002. The CDC suggests that more investigation is needed to understand this astounding increase in autism in such a short period. The aim of this pilot study was to determine whether a group of children with ASD exhibited similar variations in a broad array of potential correlates, including medical histories, symptoms, genetics, and multiple nutritional and metabolic biomarkers. This study was a retrospective, descriptive chart review. The study took place at the University of Kansas Medical Center (KUMC). Participants were 7 children with ASD who had sought treatment at the Integrative Medicine Clinic at the medical center. A majority of the children exhibited an elevated copper:zinc ratio and abnormal vitamin D levels. Children also demonstrated abnormal levels of the essential fatty acids: (1) α-linolenic acid (ALA)- C13:3W3, and (2) linoleic acid (LA)-C18:2W6; high levels of docosahexaenoic acid (DHA); and an elevated ω-6:ω-3 ratio. Three of 7 children demonstrated abnormal manganese levels. Children did not demonstrate elevated urine pyruvate or lactate but did have abnormal detoxification markers. Three of 7 patients demonstrated abnormalities in citric acid metabolites, bacterial metabolism, and fatty acid oxidation markers. A majority demonstrated elevated serum immunoglobulin G (IgG) antibodies to casein, egg whites, egg yolks, and peanuts. A majority had absent glutathione S-transferase (GSTM) at the 1p13.3 location, and 3 of 7 children were heterozygous for the glutathione S-transferase I105V (GSTP1). A majority also exhibited genetic polymorphism of the mitochondrial gene superoxide dismutase A16V (SOD2). The findings from this small group of children with ASD points

  6. Sodium Butyrate Protects -Against High Fat Diet-Induced Cardiac Dysfunction and Metabolic Disorders in Type II Diabetic Mice.

    PubMed

    Zhang, Ling; Du, Jianfeng; Yano, Naohiro; Wang, Hao; Zhao, Yu Tina; Dubielecka, Patrycja M; Zhuang, Shougang; Chin, Y Eugene; Qin, Gangjian; Zhao, Ting C

    2017-08-01

    Histone deacetylases are recently identified to act as key regulators for cardiac pathophysiology and metabolic disorders. However, the function of histone deacetylase (HDAC) in controlling cardiac performance in Type II diabetes and obesity remains unknown. Here, we determine whether HDAC inhibition attenuates high fat diet (HFD)-induced cardiac dysfunction and improves metabolic features. Adult mice were fed with either HFD or standard chow food for 24 weeks. Starting at 12 weeks, mice were divided into four groups randomly, in which sodium butyrate (1%), a potent HDAC inhibitor, was provided to chow and HFD-fed mice in drinking water, respectively. Glucose intolerance, metabolic parameters, cardiac function, and remodeling were assessed. Histological analysis and cellular signaling were examined at 24 weeks following euthanization of mice. HFD-fed mice demonstrated myocardial dysfunction and profound interstitial fibrosis, which were attenuated by HDAC inhibition. HFD-induced metabolic syndrome features insulin resistance, obesity, hyperinsulinemia, hyperglycemia, lipid accumulations, and cardiac hypertrophy, these effects were prevented by HDAC inhibition. Furthermore, HDAC inhibition attenuated myocyte apoptosis, reduced production of reactive oxygen species, and increased angiogenesis in the HFD-fed myocardium. Notably, HFD induced decreases in MKK3, p38, p38 regulated/activated protein kinase (PRAK), and Akt-1, but not p44/42 phosphorylation, which were prevented by HDAC inhibition. These results suggest that HDAC inhibition plays a critical role to preserve cardiac performance and mitigate metabolic disorders in obesity and diabetes, which is associated with MKK3/p38/PRAK pathway. The study holds promise in developing a new therapeutic strategy in the treatment of Type II diabetic-induced heart failure and metabolic disorders. J. Cell. Biochem. 118: 2395-2408, 2017. © 2017 Wiley Periodicals, Inc. © 2017 Wiley Periodicals, Inc.

  7. Variability of Creatine Metabolism Genes in Children with Autism Spectrum Disorder.

    PubMed

    Cameron, Jessie M; Levandovskiy, Valeriy; Roberts, Wendy; Anagnostou, Evdokia; Scherer, Stephen; Loh, Alvin; Schulze, Andreas

    2017-07-31

    Creatine deficiency syndrome (CDS) comprises three separate enzyme deficiencies with overlapping clinical presentations: arginine:glycine amidinotransferase ( GATM gene, glycine amidinotransferase), guanidinoacetate methyltransferase ( GAMT gene), and creatine transporter deficiency ( SLC6A8 gene, solute carrier family 6 member 8). CDS presents with developmental delays/regression, intellectual disability, speech and language impairment, autistic behaviour, epileptic seizures, treatment-refractory epilepsy, and extrapyramidal movement disorders; symptoms that are also evident in children with autism. The objective of the study was to test the hypothesis that genetic variability in creatine metabolism genes is associated with autism. We sequenced GATM , GAMT and SLC6A8 genes in 166 patients with autism (coding sequence, introns and adjacent untranslated regions). A total of 29, 16 and 25 variants were identified in each gene, respectively. Four variants were novel in GATM , and 5 in SLC6A8 (not present in the 1000 Genomes, Exome Sequencing Project (ESP) or Exome Aggregation Consortium (ExAC) databases). A single variant in each gene was identified as non-synonymous, and computationally predicted to be potentially damaging. Nine variants in GATM were shown to have a lower minor allele frequency (MAF) in the autism population than in the 1000 Genomes database, specifically in the East Asian population (Fisher's exact test). Two variants also had lower MAFs in the European population. In summary, there were no apparent associations of variants in GAMT and SLC6A8 genes with autism. The data implying there could be a lower association of some specific GATM gene variants with autism is an observation that would need to be corroborated in a larger group of autism patients, and with sub-populations of Asian ethnicities. Overall, our findings suggest that the genetic variability of creatine synthesis/transport is unlikely to play a part in the pathogenesis of autism spectrum

  8. Diagnosis of rare inherited glyoxalate metabolic disorders through in-situ analysis of renal stones

    NASA Astrophysics Data System (ADS)

    Jacob, D. E.; Grohe, B.; Hoppe, B.; Beck, B. B.; Tessadri, R.

    2012-04-01

    The primary hyperoxalurias type I - III constitute rare autosomal-recessive inherited disorders of the human glyoxylate metabolism. By mechanisms that are ill understood progressive nephrocalcinosis and recurrent urolithiasis (kidney stone formation) often starting in early childhood, along with their secondary complications results in loss of nephron mass which progresses to end-stage renal failure over time. In the most frequent form, end-stage renal failure (ESRF) is the rule and combined liver/kidney transplantation respectively pre-emptive liver transplantation are the only causative treatment today. Hence, this contributes significantly to healthcare costs and early diagnosis is extremely important for a positive outcome for the patient. We are developing a stone-based diagnostic method by in-detail multi-methods investigation of the crystalline moiety in concert with urine and stone proteomics. Stone analysis will allow faster analysis at low-impact for the patients in the early stages of the disease. First results from combined spectroscopic (Raman, FTIR)and geochemical micro-analyses (Electron Microprobe and Laser Ablation ICP-MS) are presented here that show significant differences between stones from hyperoxaluria patients and those formed by patients without this disorder (idiopathic stones). Major differences exist in chemistry as well as in morphology and phase composition of the stones. Ca/P ratios and Mg contents differentiate between oxalate-stones from hyperoxaluria patients and idiopathic stones. Results show that also within the different subtypes of primary hyperoxaluria significant differences can be found in stone composition. These imply differences in stone formation which could be exploited for new therapeutic pathways. Furthermore, the results provide important feedback for suspected but yet unconfirmed cases of primary hyperoxaluria when used in concert with the genetic methods routinely applied.

  9. Altered erythrocyte nucleotide patterns are characteristic of inherited disorders of purine or pyrimidine metabolism.