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Sample records for cobalamin deficiency hyperhomocysteinemia

  1. Cobalamin deficiency, hyperhomocysteinemia, and dementia

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    Steven F Werder

    2010-04-01

    Full Text Available Steven F Werder1,21Kansas University School of Medicine – Wichita, Wichita, KS, USA; 2Community Health Center of Southeast Kansas, Pittsburg, KS, USAIntroduction: Although consensus guidelines recommend checking serum B12 in patients with dementia, clinicians are often faced with various questions: (1 Which patients should be tested? (2 What test should be ordered? (3 How are inferences made from such testing? (4 In addition to serum B12, should other tests be ordered? (5 Is B12 deficiency compatible with dementia of the Alzheimer’s type? (6 What is to be expected from treatment? (7 How is B12 deficiency treated?Methods: On January 31st, 2009, a Medline search was performed revealing 1,627 citations related to cobalamin deficiency, hyperhomocysteinemia, and dementia. After limiting the search terms, all abstracts and/or articles and other references were categorized into six major groups (general, biochemistry, manifestations, associations and risks, evaluation, and treatment and then reviewed in answering the above questions.Results: The six major groups above are described in detail. Seventy-five key studies, series, and clinical trials were identified. Evidence-based suggestions for patient management were developed.Discussion: Evidence is convincing that hyperhomocysteinemia, with or without hypovitaminosis B12, is a risk factor for dementia. In the absence of hyperhomocysteinemia, evidence is less convincing that hypovitaminosis B12 is a risk factor for dementia. B12 deficiency manifestations are variable and include abnormal psychiatric, neurological, gastrointestinal, and hematological findings. Radiological images of individuals with hyperhomocysteinemia frequently demonstrate leukoaraiosis. Assessing serum B12 and treatment of B12 deficiency is crucial for those cases in which pernicious anemia is suspected and may be useful for mild cognitive impairment and mild to moderate dementia. The serum B12 level is the standard initial test

  2. Pyridoxal-5'-phosphate deficiency is associated with hyperhomocysteinemia regardless of antioxidant, thiamine, riboflavin, cobalamine, and folate status in critically ill patients.

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    Molina-López, Jorge; Florea, Daniela; Quintero-Osso, Bartolomé; de la Cruz, Antonio Pérez; Rodríguez-Elvira, Manuel; Del Pozo, Elena Planells

    2016-06-01

    was only associated with hyperhomocysteinemia regardless of antioxidant, riboflavin, cobalamine, and folate statuses in critically ill patients with SIRS at seventh day of ICU stay. PLP deficient patients presented about six times more risk of cardiovascular disease than non deficients. Copyright © 2015 Elsevier Ltd and European Society for Clinical Nutrition and Metabolism. All rights reserved.

  3. Cobalamin Deficiency in Elderly Patients: A Personal View

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    Emmanuel Andrès

    2008-01-01

    Full Text Available Cobalamin (vitamin B12 deficiency is particularly common in the elderly (>65 years of age but is often unrecognized because its clinical manifestations are subtle; however, they are also potentially serious, particularly from a neuropsychiatric and hematological perspective. In the elderly, the main causes of cobalamin deficiency are pernicious anemia and food-cobalamin malabsorption. Food-cobalamin malabsorption syndrome is a disorder characterized by the inability to release cobalamin from food or its binding proteins. This syndrome is usually caused by atrophic gastritis, related or unrelated to Helicobacter pylori infection, and long-term ingestion of antacids and biguanides. Management of cobalamin deficiency with cobalamin injections is currently well documented but new routes of cobalamin administration (oral and nasal are being studied, especially oral cobalamin therapy for food-cobalamin malabsorption.

  4. Cobalamin Deficiency: Clinical Picture and Radiological Findings

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    Chiara Briani

    2013-11-01

    Full Text Available Vitamin B12 deficiency causes a wide range of hematological, gastrointestinal, psychiatric and neurological disorders. Hematological presentation of cobalamin deficiency ranges from the incidental increase of mean corpuscular volume and neutrophil hypersegmentation to symptoms due to severe anemia, such as angor, dyspnea on exertion, fatigue or symptoms related to congestive heart failure, such as ankle edema, orthopnea and nocturia. Neuropsychiatric symptoms may precede hematologic signs and are represented by myelopathy, neuropathy, dementia and, less often, optic nerve atrophy. The spinal cord manifestation, subacute combined degeneration (SCD, is characterized by symmetric dysesthesia, disturbance of position sense and spastic paraparesis or tetraparesis. The most consistent MRI finding is a symmetrical abnormally increased T2 signal intensity confined to posterior or posterior and lateral columns in the cervical and thoracic spinal cord. Isolated peripheral neuropathy is less frequent, but likely overlooked. Vitamin B12 deficiency has been correlated negatively with cognitive functioning in healthy elderly subjects. Symptoms include slow mentation, memory impairment, attention deficits and dementia. Optic neuropathy occurs occasionally in adult patient. It is characterized by symmetric, painless and progressive visual loss. Parenteral replacement therapy should be started soon after the vitamin deficiency has been established.

  5. Cobalamin C deficiency in an adolescent with altered mental status and anorexia.

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    Rahmandar, Maria H; Bawcom, Amanda; Romano, Mary E; Hamid, Rizwan

    2014-12-01

    Although cobalamin (cbl) C deficiency is the most common inherited disorder of vitamin B12 metabolism, the late-onset form of the disease can be difficult to recognize because it has a broad phenotypic spectrum. In this report, we describe an adolescent female exposed to unknown illicit substances and sexual abuse who presented with psychosis, anorexia, seizures, and ataxia. The patient's diagnosis was delayed until a metabolic workup was initiated, revealing hyperhomocysteinemia, low normal plasma methionine, and methylmalonic aciduria. Ultimately, cblC deficiency was confirmed when molecular testing showed compound heterozygosity for mutations (c.271dupA and c.482G>A) in the MMACHC gene. This diagnosis led to appropriate treatment with hydroxocobalamin, betaine, and folate, which resulted in improvement of her clinical symptoms and laboratory values. This patient demonstrates a previously unrecognized presentation of late-onset cblC deficiency. Although neuropsychiatric symptoms are common in late-onset disease, seizures and cerebellar involvement are not. Furthermore, anorexia has not been previously described in these patients. This case emphasizes that inborn errors of metabolism should be part of the differential diagnosis for a teenager presenting with altered mental status, especially when the diagnosis is challenging or neurologic symptoms are unexplained. Correct diagnosis of this condition is important because treatment is available and can result in clinical improvement.(1.) Copyright © 2014 by the American Academy of Pediatrics.

  6. Clinical aspects of cobalamin deficiency in elderly patients. Epidemiology, causes, clinical manifestations, and treatment with special focus on oral cobalamin therapy.

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    Andrès, Emmanuel; Vidal-Alaball, Josep; Federici, Laure; Loukili, Noureddine Henoun; Zimmer, Jacques; Kaltenbach, Georges

    2007-10-01

    The aim of this work was to review the literature concerning cobalamin deficiency in elderly patients. Articles were identified through searches of PubMed-MEDLINE (January 1990 to June 2006), restricted to: English and French language, human subjects, elderly patients (>65 years), clinical trial, review and guidelines. Additional unpublished data from our cohort with cobalamin deficiency at the University Hospital of Strasbourg, France, were also considered. All of the papers and abstracts were reviewed by at least two senior researchers who selected the data used in the study. In elderly people, the main causes of cobalamin deficiency are pernicious anemia and food-cobalamin malabsorption. The recently identified food-cobalamin malabsorption syndrome is a disorder characterized by the inability to release cobalamin from food or from its binding proteins. This syndrome is usually the consequence of atrophic gastritis, related or not to Helicobacter pylori infection, and of the long-term ingestion of antacids and biguanides (in around 60% of the patients). Management of cobalamin deficiency has been well established with the use of cobalamin injections. However, new routes of cobalamin administration (oral and nasal) are currently being developed, especially the use of oral cobalamin therapy to treat food-cobalamin malabsorption.

  7. Influence of duration and dose of metformin on cobalamin deficiency in type 2 diabetes patients using metformin

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    Beulens, Joline W J; Hart, Huberta E.; Kuijs, Ron; Kooijman-Buiting, Antoinette M J; Rutten, Guy E H M

    2015-01-01

    Metformin use is associated with cobalamin (vitamin B12) deficiency. However, the influence of both duration and dose of metformin is unclear. Studies using holotranscobalamin, a marker for cellular cobalamin deficiency, are scarce. We therefore investigated the prevalence of cobalamin deficiency in

  8. Effects of betaine supplementation and choline deficiency on folate deficiency-induced hyperhomocysteinemia in rats.

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    Liu, Ying; Liu, Yi-qun; Morita, Tatsuya; Sugiyama, Kimio

    2012-01-01

    The effect of betaine status on folate deficiency-induced hyperhomocysteinemia was investigated to determine whether folate deficiency impairs homocysteine removal not only by the methionine synthase (MS) pathway but also by the betaine-homocysteine S-methyltransferase (BHMT) pathway. For this purpose, we investigated the effect of dietary supplementation with betaine at a high level (1%) in rats fed a folate-deprived 10% casein diet (10C) and 20% casein diet (20C). We also investigated the effect of choline deprivation on folate deficiency-induced hyperhomocysteinemia in rats fed 20C. Supplementation of folate-deprived 10C and 20C with 1% betaine significantly suppressed folate deprivation-induced hyperhomocysteinemia, but the extent of suppression was partial or limited, especially in rats fed 10C, the suppression of plasma homocysteine increment being 48.5% in rats fed 10C and 69.7% in rats fed 20C. Although betaine supplementation greatly increased hepatic betaine concentration and BHMT activity, these increases did not fully explain why the effect of betaine supplementation was partial or limited. Folate deprivation markedly increased the hepatic concentration of N,N-dimethylglycine (DMG), a known inhibitor of BHMT, and there was a significant positive correlation between hepatic DMG concentration and plasma homocysteine concentration, suggesting that folate deficiency increases hepatic DMG concentration and thereby depresses BHMT reaction, leading to interference with the effect of betaine supplementation. Choline deprivation did not increase plasma homocysteine concentration in rats fed 20C, but it markedly enhanced plasma homocysteine concentration when rats were fed folate-deprived 20C. This indicates that choline deprivation reinforced folate deprivation-induced hyperhomocysteinemia. Increased hepatic DMG concentration was also associated with such an effect. These results support the concept that folate deficiency impairs homocysteine metabolism not only

  9. Relationship between cobalamin deficiency and delirium in elderly patients undergoing cardiac surgery

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    Sevuk U

    2015-08-01

    Full Text Available Utkan Sevuk,1 Erkan Baysal,2 Nurettin Ay,3 Yakup Altas,2 Rojhat Altindag,2 Baris Yaylak,2 Vahhac Alp,3 Ertan Demirtas4 1Department of Cardiovascular Surgery, Diyarbakir Gazi Yasargil Education and Research Hospital, Diyarbakir, 2Department of Cardiology, Diyarbakir Gazi Yasargil Education and Research Hospital, Diyarbakir, 3Department of General Surgery, Diyarbakir Gazi Yasargil Education and Research Hospital, Diyarbakir, 4Department of Cardiovascular Surgery, Liv Hospital, Ankara, Turkey Background: Delirium is common after cardiac surgery and is independently associated with increased morbidity, mortality, prolonged hospital stays, and higher costs. Cobalamin (vitamin B12 deficiency is a common cause of neuropsychiatric symptoms and affects up to 40% of elderly people. The relationship between cobalamin deficiency and the occurrence of delirium after cardiac surgery has not been examined in previous studies. We examined the relationship between cobalamin deficiency and delirium in elderly patients undergoing coronary artery bypass grafting (CABG surgery.Material and methods: A total of 100 patients with cobalamin deficiency undergoing CABG were enrolled in this retrospective study. Control group comprised 100 patients without cobalamin deficiency undergoing CABG. Patients aged 65 years or over were included. Diagnosis of delirium was made using Intensive Care Delirium Screening Checklist. Delirium severity was measured using the Delirium Rating Scale-revised-98.Results: Patients with cobalamin deficiency had a significantly higher incidence of delirium (42% vs 26%; P=0.017 and higher delirium severity scores (16.5±2.9 vs 15.03±2.48; P=0.034 than patients without cobalamin deficiency. Cobalamin levels were significantly lower in patients with delirium than patients without delirium (P=0.004. Delirium severity score showed a moderate correlation with cobalamin levels (Ρ=-0.27; P=0.024. Logistic regression analysis demonstrated that

  10. Deficiency of superoxide dismutase promotes cerebral vascular hypertrophy and vascular dysfunction in hyperhomocysteinemia.

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    Sanjana Dayal

    Full Text Available There is an emerging consensus that hyperhomocysteinemia is an independent risk factor for cerebral vascular disease and that homocysteine-lowering therapy protects from ischemic stroke. However, the mechanisms by which hyperhomocysteinemia produces abnormalities of cerebral vascular structure and function remain largely undefined. Our objective in this study was to define the mechanistic role of superoxide in hyperhomocysteinemia-induced cerebral vascular dysfunction and hypertrophy. Unlike previous studies, our experimental design included a genetic approach to alter superoxide levels by using superoxide dismutase 1 (SOD1-deficient mice fed a high methionine/low folate diet to produce hyperhomocysteinemia. In wild-type mice, the hyperhomocysteinemic diet caused elevated superoxide levels and impaired responses to endothelium-dependent vasodilators in cerebral arterioles, and SOD1 deficiency compounded the severity of these effects. The cross-sectional area of the pial arteriolar wall was markedly increased in mice with SOD1 deficiency, and the hyperhomocysteinemic diet sensitized SOD1-deficient mice to this hypertrophic effect. Analysis of individual components of the vascular wall demonstrated a significant increase in the content of smooth muscle and elastin. We conclude that superoxide is a key driver of both cerebral vascular hypertrophy and vasomotor dysfunction in this model of dietary hyperhomocysteinemia. These findings provide insight into the mechanisms by which hyperhomocysteinemia promotes cerebral vascular disease and ischemic stroke.

  11. Cobalamin deficiency associated with erythroblastic anemia and methylmalonic aciduria in a border collie.

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    Morgan, L W; McConnell, J

    1999-01-01

    Anemia due to cobalamin deficiency is a rare genetic disorder that has been recognized in dogs only recently. This report concerns a 14-month-old border collie that presented for chronic, nonregenerative anemia. Cytological examination of a peripheral blood smear showed the presence of erythroblasts. Serum cobalamin levels were below reference ranges reported for clinically normal dogs. A methylmalonic aciduria was found on urinalysis. These signs are consistent with the anemia in Imerslund-Graesbeck syndrome reported in humans. Anemia due to cobalamin deficiency responds to parenteral vitamin B12 therapy, and affected animals have a good prognosis for recovery.

  12. Hyperammonaemic encephalopathy secondary to selective cobalamin deficiency in a juvenile Border collie.

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    Battersby, I A; Giger, U; Hall, E J

    2005-07-01

    An eight-month-old Border collie was presented with anorexia, cachexia, failure to thrive and stupor. Laboratory tests demonstrated a mild anaemia, neutropenia, proteinuria and hyperammonaemia. Serum bile acid concentrations were normal, but an ammonia tolerance test (ATT) was abnormal. The dog responded to symptomatic therapy for hepatoencephalopathy. When a low serum cobalamin (vitamin B12) concentration and methylmalonic aciduria were noted, the dog was given a supplement of parenteral cobalamin. Two weeks later, a repeat ATT was normal. Cobalamin supplementation was continued every two weeks, and all clinical signs, except for proteinuria, resolved despite withdrawing all therapy for hepatoencephalopathy. A presumptive diagnosis of hereditary selective cobalamin malabsorption was made, based on the young age, Border collie breed, low serum cobalamin concentration and methylmalonic aciduria. Although hereditary selective cobalamin malabsorption in Border collies, giant schnauzers, Australian shepherd dogs and beagles has previously been reported in North America, to the authors' knowledge this is the first report of the condition in the UK and the first to document an abnormal ATT in a cobalamin-deficient dog.

  13. Thrombotic CV Stroke in a Young Male with Hyperhomocysteinemia and Protein S Deficiency: A Case Report

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    Nilima Shah

    2014-12-01

    Full Text Available Stroke in young poses a major health problem. Thrombophilic factors have been implicated in 4-8% of the young strokes worldwide. Hyperhomocysteinemia is an independent risk factor for atherosclerosis but there are few data regarding its role in acute arterial thrombosis without any previous lesion. Overall estimated incidence of deep vein thrombosis is 1 per 1000 persons with Protein S deficiency but very few studies suggest association between arterial thrombosis with Protein S deficiency. We present a case of 18 year old boy who presented to us with acute onset right sided hemiplegia and aphasia whose laboratory findings were suggestive of hyperhomocyseinemia and Protein S deficiency.

  14. Diagnosis and management of clinical and subclinical cobalamin deficiencies: why controversies persist in the age of sensitive metabolic testing.

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    Carmel, Ralph

    2013-05-01

    In the past two decades, sensitive biochemical tests have uncovered cobalamin deficiency much more frequently than ever before. Almost all cases involve mild, biochemical changes without clinical manifestations (subclinical cobalamin deficiency; SCCD), whose health impact is unclear. Because the causes of SCCD are most often unknown, nonmalabsorptive, and seldom documented, controversy and confusion surround the diagnostic criteria and, inevitably, consequences and management of SCCD. To complicate matters, our grasp of the rarer clinical deficiency, usually a serious, progressive medical disease rooted in severe malabsorption, has receded as absorption testing has disappeared. Reexamining the accumulation of assumptions and misperceptions about cobalamin deficiency and distinguishing SCCD from clinical deficiency is long overdue. The biology of cobalamin provides an important starting point: cobalamin stores exceed daily losses so greatly and binding proteins regulate absorption so effectively that deficiency typically achieves clinical expression only after years of severe, relentless malabsorption. Dietary insufficiency, mild, partial malabsorption, and other incomplete, intermittent causes can usually produce only SCCD. Thus, the most fundamental difference between the two deficiencies is the relentlessness of the underlying cause, which determines prognosis and health impact. Inattention to absorptive status has exacerbated the limitations of biochemical testing. All the biochemical tests are highly sensitive but specificity is poor, no diagnostic gold standard exists, and diagnostic cutpoints fluctuate excessively. To limit the adverse diagnostic consequences, the diagnosis of SCCD, whose need for treatment is unclear, should be deferred unless at least two tests are abnormal. Indeed, cobalamin biology indicates that the absorption system, while enhancing cobalamin delivery, also sets a strict upper limit on it, which suggests that cobalamin excess is

  15. Iron, folate and cobalamin deficiency in anaemic pregnant females in tertiary care centre at Rawalpindi

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    Khan, D A; Fatima, S; Imran, R; Khan, F A [National Univ. of Science and Technology, Army Medical College, Rawalpindi (Pakistan). Department of Pathology

    2010-01-15

    Background: Anaemia in pregnancy is a common clinical problem contributing to increased maternal and foetal morbidity. This study was carried out to determine frequency of iron, folate and cobalamin deficiency and associated risk factors in the anaemic pregnant females who reported first time during second and third trimester for antenatal check-up in the tertiary care hospital at Rawalpindi. Methods: This case control study was carried out in a tertiary care hospital at Rawalpindi. Two hundred and fifty pregnant women (age: 19-43 years) consisting of 125 anaemic (Hb< 110 g/L) and 125 non-anaemic who reported first time at antenatal clinic were included. Data on socio-demographic characteristics, parity and dietary intake were collected. Complete blood counts were done. Serum ferritin, folate and cobalamin assays were performed by using DPC kits on Immulite-1000. Results: The pregnant women were categorised having mild (Hb up to 54%), moderate (Hb up to 36%), or severe (Hb up to 10%) anaemia during antennal visit. They had significantly lower median (range) levels of haemoglobin 96 (40-110) g/L, ferritin 8 (3-54) nu mu/L, folate 15 (3-54) mu mol/L and cobalamin 171 (111-629) mu mol/L than controls (p=<0.01). Micro nutrient analysis revealed secondary pregnancy related deficiency of Iron (57%), folate (20%), combined iron and folate (19%) and cobalamin (4%) in the female. Among the risk factors, low income (OR: 7.69), multi party (OR: 2.93), lack of iron/folate supplementation (OR 2.91) and inadequate dietary intakes (OR 2.51) were associated with anaemia. Conclusion: The pregnant anaemic women had iron (57%); folate (20%), followed by combined iron folate (19%), and cobalamin (4%) deficiency during first antenatal visit. Low income, multi party, poor diet and lack of supplements are the main contributor in development of anaemia during pregnancy. (author)

  16. Iron, folate and cobalamin deficiency in anaemic pregnant females in tertiary care centre at Rawalpindi

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    Khan, D.A.; Fatima, S.; Imran, R.; Khan, F.A.

    2010-01-01

    Background: Anaemia in pregnancy is a common clinical problem contributing to increased maternal and foetal morbidity. This study was carried out to determine frequency of iron, folate and cobalamin deficiency and associated risk factors in the anaemic pregnant females who reported first time during second and third trimester for antenatal check-up in the tertiary care hospital at Rawalpindi. Methods: This case control study was carried out in a tertiary care hospital at Rawalpindi. Two hundred and fifty pregnant women (age: 19-43 years) consisting of 125 anaemic (Hb< 110 g/L) and 125 non-anaemic who reported first time at antenatal clinic were included. Data on socio-demographic characteristics, parity and dietary intake were collected. Complete blood counts were done. Serum ferritin, folate and cobalamin assays were performed by using DPC kits on Immulite-1000. Results: The pregnant women were categorised having mild (Hb up to 54%), moderate (Hb up to 36%), or severe (Hb up to 10%) anaemia during antennal visit. They had significantly lower median (range) levels of haemoglobin 96 (40-110) g/L, ferritin 8 (3-54) nu mu/L, folate 15 (3-54) mu mol/L and cobalamin 171 (111-629) mu mol/L than controls (p=<0.01). Micro nutrient analysis revealed secondary pregnancy related deficiency of Iron (57%), folate (20%), combined iron and folate (19%) and cobalamin (4%) in the female. Among the risk factors, low income (OR: 7.69), multi party (OR: 2.93), lack of iron/folate supplementation (OR 2.91) and inadequate dietary intakes (OR 2.51) were associated with anaemia. Conclusion: The pregnant anaemic women had iron (57%); folate (20%), followed by combined iron folate (19%), and cobalamin (4%) deficiency during first antenatal visit. Low income, multi party, poor diet and lack of supplements are the main contributor in development of anaemia during pregnancy. (author)

  17. The Effects of Methionine-Enriched and Vitamins (Folate, Pyridoxine and Cobalamine-Deficient Diet on Exploratory Activity in Rats - A Brief Report

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    Mijailovic Natasa

    2017-12-01

    Full Text Available The aim of this study was to evaluate the impact of increased homocysteine levels induced by methionine nutritional overload (twice as standard and deficiency of the vitamins folate, pyridoxine and cobalamine, which plays an important role in homocysteine metabolism in anxiety-related behaviour, expressed by means of exploratory activity in rats. Twenty-three male Wistar albino rats (4 weeks old, 100±15 g body weight were divided into three groups: control (n=8, methionine-enriched (Meth+, 7.7 g of methionine/kg chow, n=7 and methionine-enriched vitamin-deficient (Meth+Vit-, 7.7 g of methionine/ kg chow, deficient in folate, pyridoxine and cobalamine - 0.08, 0.01 and 0.01 mg/kg, n=8. All animals had free access to food and water for 30 days. Behavioural testing was performed using the elevated plus maze (EPM test. Standard parameters for vertical exploratory activity, the number of rearings and the number of head-dippings, as well as the total exploratory activity (summarizing overall exploratory activity in the EPM were significantly reduced following 30 days of methionine nutritional overload (p<0.05, p<0.05 and p<0.01, respectively. A methionine-enriched diet coupled with a reduction in some B vitamins resulted in a more pronounced decline in exploratory drive observed in the EPM test compared to the control (p<0.01. The decline in total exploratory activity associated with vitamin deficiency was significant compared to the Meth+ group (p<0.05. The results of this study highlight the important role of homocysteine in the modulation of exploratory activity in rats. Decreased exploratory drive induced by both a methionine-enriched and vitamin-deficient diet could be attributed to an anxiogenic effect of hyperhomocysteinemia.

  18. METHYLMALONIC ACID AND HOMOCYSTEIN SERUM IN DIAGNOSING MEGALOBLASTIC ANEMIA DUE TO COBALAMIN AND FOLATE DEFICIENCY IN TRAVEL MEDICINE

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    Made Gian Indra Rahayuda

    2014-01-01

    Full Text Available Normal 0 false false false EN-US X-NONE X-NONE Anemia is a major global health problem, especially in developing countries. Anemia is a condition where the red blood cell mass and / or hemoglobin mass that circulating in the body was decreased to below normal level so it can not function well in providing oxygen to the body tissues. One of the most common type is megaloblastic anemia. Megaloblastic anemia is mostly caused by vitamin B12 (cobalamin and folate deficiency. One of the causes of cobalamin and folate deficiency anemia is tropical sprue. Cobalamin deficiency anemia and folate deficiency anemia gives a similar symptom, but in cobalamin deficiency there is neuropathy symptoms. Normal serum folate is between 3-15 ng/mL. Normal folate erythrocyte is 150-600 ng/mL. In cobalamin deficiency, serum cobalamin decreased below the cut off point 100pg/mL (normally 100 - 400pg/mL. Other examination such as elevated homocysteine??, methylmalonic acid, or formioglutamic acid (FIGLU in the urine can confirm the diagnosis of cobalamin and folic acid deficiency. There is no consensus on the cut-off point of homocysteine ??and MMA. Homocysteine ??has been considered to increase when the levels are above 12-14 ?mol /L in women and in the 14-15 ?mol/L. According to research by Robert et al in the case of cobalamin deficiency, serum tHcy> 15.0 ?mol/L. Most research considers the increase of MMA in cobalamin deficiency is> 0:28 ?mol / L, but the cut off point in circulation varies between 0:21 to 0:48 ?mol/L. MMA level is increased in serum and urine in cobalamin deficiency, whereas MMA normal in folate deficiency. /* Style Definitions */ table.MsoNormalTable {mso-style-name:"Table Normal"; mso-tstyle-rowband-size:0; mso-tstyle-colband-size:0; mso-style-noshow:yes; mso-style-priority:99; mso-style-qformat:yes; mso-style-parent:""; mso-padding-alt:0in 5.4pt 0in 5.4pt; mso-para-margin:0in; mso-para-margin-bottom:.0001pt; mso-pagination:widow-orphan; font

  19. Systemic Scedosporium prolificans infection in an 11-month-old Border collie with cobalamin deficiency secondary to selective cobalamin malabsorption (canine Imerslund-Gräsbeck syndrome).

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    Erles, K; Mugford, A; Barfield, D; Leeb, T; Kook, P H

    2018-04-01

    An 11-month-old Border collie presented collapsed and continued to deteriorate rapidly despite supportive treatment. The dog had a history of failure to thrive and recurring respiratory infection. Laboratory abnormalities included neutrophilic leucocytosis, Heinz body anaemia, hyperammonaemia, hyperbilirubinaemia, proteinuria and hypocobalaminaemia. Post-mortem examination revealed multi-focal necrosis within the heart, kidneys, pancreas, liver, meninges and cerebral cortex. Fungal hyphae in lesions were identified as Scedosporium prolificans following culture. Subsequent genotyping confirmed that the dog carried the CUBN:c.8392delC mutation in a homozygous state, verifying hereditary cobalamin deficiency (a.k.a. Imerslund-Gräsbeck syndrome). Cobalamin deficiency may have been a predisposing factor for the development of systemic fungal infection in this dog. © 2017 British Small Animal Veterinary Association.

  20. Pernicious Anemia Associated Cobalamin Deficiency and Thrombotic Microangiopathy: Case Report and Review of the Literature

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    Farhanah Yousaf

    2017-01-01

    Full Text Available A 43-year-old Hispanic male without significant previous medical history was brought to emergency department for syncope following a blood draw to investigate a 40 lbs weight loss during the past 6 months associated with decreased appetite and progressive fatigue. The patient also reported a 1-month history of jaundice. On examination, he was hemodynamically stable and afebrile with pallor and diffuse jaundice but without skin rash or palpable purpura. Normal sensations and power in all extremities were evident on neurological exam. Presence of hemolytic anemia, schistocytosis, thrombocytopenia, and elevated lactate dehydrogenase (LDH was suggestive of thrombotic thrombocytopenic purpura (TTP. However, presence of leukopenia, macrocytes, and an inadequate reticulocyte response to the degree of anemia served as initial clues to an alternative diagnosis. Two and one units of packed red blood cells were transfused on day 1 and day 3, respectively. In addition, one unit of platelets was transfused on day 2. Daily therapeutic plasma exchange (TPE was initiated and continued until ADAMTS-13 result ruled out TTP. A low cobalamin (vitamin B12 level was evident at initial laboratory work-up and subsequent testing revealed positive intrinsic factor-blocking antibodies supporting a diagnosis of pernicious anemia with severe cobalamin deficiency. Hematological improvement was observed following vitamin B12 supplementation. The patient was discharged and markedly improved on day 9 with outpatient follow-up for cobalamin supplementation.

  1. Cobalamin Deficiency Results in Increased Production of Formate Secondary to Decreased Mitochondrial Oxidation of One-Carbon Units in Rats.

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    MacMillan, Luke; Tingley, Garrett; Young, Sara K; Clow, Kathy A; Randell, Edward W; Brosnan, Margaret E; Brosnan, John T

    2018-03-01

    Formate is produced in mitochondria via the catabolism of serine, glycine, dimethylglycine, and sarcosine. Formate produced by mitochondria may be incorporated into the cytosolic folate pool where it can be used for important biosynthetic reactions. Previous studies from our lab have shown that cobalamin deficiency results in increased plasma formate concentrations. Our goal was to determine the basis for elevated formate in vitamin B-12 deficiency. Male Sprague Dawley rats were randomly assigned to consume either a cobalamin-replete (50 μg cobalamin/kg diet) or -deficient (no added cobalamin) diet for 6 wk. Formate production was measured in vivo and in isolated liver mitochondria from a variety of one-carbon precursors. We also measured the oxidation of [3-14C]-l-serine to 14CO2 in isolated rat liver mitochondria and the expression of hepatic genes involved in one-carbon unit and formate metabolism. Cobalamin-deficient rats produce formate at a rate 55% higher than that of replete rats. Formate production from serine was increased by 60% and from dimethylglycine and sarcosine by ∼200% in liver mitochondria isolated from cobalamin-deficient rats compared with cobalamin-replete rats. There was a 26% decrease in the 14CO2 produced by mitochondria from cobalamin-deficient rats. Gene expression analysis showed that 10-formyltetrahydrofolate dehydrogenase-cytosolic (Aldh1l1) and mitochondrial (Aldh1l2) expression were decreased by 40% and 60%, respectively, compared to control, while 10-formyltetrahydrofolate synthetase, mitochondrial, monofunctional (Mthfd1l) expression was unchanged. We propose that a bifurcation in mitochondrial one-carbon metabolism is a key control mechanism in determining the fate of one-carbon units, to formate or CO2. During cobalamin deficiency in rats the disposition of 10-formyl-tetrahydrofolate carbon is shifted in favor of formate production. This may represent a mechanism to generate more one-carbon units for the replenishment of the S

  2. Suppression Effects of Betaine-Enriched Spinach on Hyperhomocysteinemia Induced by Guanidinoacetic Acid and Choline Deficiency in Rats

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    Yi-Qun Liu

    2014-01-01

    Full Text Available Betaine is an important natural component of rich food sources, especially spinach. Rats were fed diets with betaine or spinach powder at the same level of betaine for 10 days to investigate the dose-dependent effects of spinach powder supplementation on hyperhomocysteinemia induced by guanidinoacetic acid (GAA addition and choline deprivation. The GAA-induced hyperhomocysteinemia in rats fed 25% casein diet (25C was significantly suppressed by supplementation with betaine or spinach, and it was completely suppressed by taking 11.0% spinach supplementation. The choline deprivation-induced enhancement of plasma homocysteine concentration in rats fed 25% soybean protein diet (25S was markedly suppressed by 3.82% spinach. Supplementation with betaine or spinach partially prevented the effects of GAA on hepatic concentrations of methionine metabolites. The decrease in activity of betaine-homocysteine S-methyltransferase (BHMT and cystathionine β-synthase (CBS in GAA-induced hyperhomocysteinemia was recovered by supplementation with betaine or spinach. Supplementation with betaine or spinach did not affect BHMT activity, whereas it partially restored CBS activity in choline-deprived 25S. The results indicated that betaine or spinach could completely suppress the hyperhomocysteinemia induced by choline deficiency resulting from stimulating the homocysteine removal by both remethylation and cystathionine formation.

  3. Advanced glycation end products overload might explain intracellular cobalamin deficiency in renal dysfunction, diabetes and aging.

    Science.gov (United States)

    Obeid, Rima; Shannan, Batool; Herrmann, Wolfgang

    2011-11-01

    Advanced glycation end products (AGEs) contribute to aging. Cobalamin (Cbl) is required for cell growth and functions, and its deficiency causes serious complications. Diabetics and renal patients show high concentrations of Cbl, but metabolic evidence of Cbl deficiency that is reversible after Cbl treatment. Cbl might be sequestered in blood and cannot be delivered to the cell. Megalin mediates the uptake of transcobalamin-Cbl complex into the proximal tubule cells. Megalin is involved in the uptake and degradation of AGEs. In aging, diabetes or renal dysfunction, AGEs might overload megalin thus lowering Cbl uptake. Transcobalamin-Cbl might retain in blood. Shedding of megalin and transcobalamin receptor under glycation conditions is also a possible mechanism of this phenomenon. Copyright © 2011 Elsevier Ltd. All rights reserved.

  4. COGNITIVE IMPAIRMENTS IN VITAMIN B12 AND FOLIC ACID DEFICIENCIES AND HYPERHOMOCYSTEINEMIA

    Directory of Open Access Journals (Sweden)

    P. R. Kamchatnov

    2015-01-01

    Full Text Available Vitamin metabolic disorders can cause diverse dysfunctions of both the peripheral and central nervous systems. There is conclusive evidence that cyanocobalamin (vitamin B12 and folic acid deficiencies may lead to diminished cognitive functions even to the extent of developing dementia. Cognitive impairments may be accompanied by involvement of other regions of the central nervous system, the corticospinal tract in particular, less frequently by brainstem and cerebellar disorders. Changes in nervous system functions in the presence of cyanocobalamin deficiency may predominate in the clinical picture, ahead of the occurrence of hematological changes. The paper considers the possible mechanisms for involvement of brain neurons in deficiency of cyanocobalamin and in that of folic acid in particular in patients with hyperhomocysteinemia. The low serum concentration of folic acid or cyanocobalamin in the elderly raises the risk of developing Alzheimer’s disease in future (by almost twice and vascular dementia. The authors give the results of randomized clinical trials evaluating the efficacy of the vitamins used in patients with cognitive impairments. Thus, there are data that the use of cyanocobalamin in patients with lacunar infarcts and moderate cognitive impairments may give rise to their complete recovery and reduce the risk of depressive disorders. Intramuscular cyanocobalamin used in a daily dose of 1000 μg for 5 days, then 1000 μg once monthly is demonstrated to be efficacious. This therapy may be effective in patients with different types of dementia and cognitive diminution, primarily in those with these conditions and its serum concentration of less 150 pmol/l. Among the side effects while taking folic acid, there may be higher incidence rates of convulsive attacks. A number of trials have shown the efficacy of cyanocobalamin, pyridoxine, and folic acid in preventing acute cerebral ischemic episodes; however, not all the investigations

  5. The marker of cobalamin deficiency, plasma methylmalonic acid, correlates to plasma creatinine

    DEFF Research Database (Denmark)

    Hvas, A M; Juul, S; Gerdes, Lars Ulrik

    2000-01-01

    OBJECTIVE: To examine the relationship between the two diagnostic tests, plasma methylmalonic acid and plasma cobalamins, and their association with plasma creatinine, age and sex. DESIGN: Cross-sectional study of simultaneous laboratory measurements. SETTING: County of Aarhus, Denmark. SUBJECTS......: Records on 1689 patients who had their first plasma methylmalonic acid measurement during 1995 and 1996, and who had a simultaneous measurement of plasma cobalamins. Plasma creatinine values measured within a week of measurements of plasma methylmalonic acid and plasma cobalamins were available for 1255...... of the patients. MAIN OUTCOME MEASURES: Predictors of variation in plasma methylmalonic acid; plasma cobalamins, plasma creatinine, age and sex. RESULTS: Plasma methylmalonic acid was positively correlated with plasma creatinine, even for plasma creatinine within the normal range. These associations remained...

  6. High prevalence of mild hyperhomocysteinemia and folate, B/sub 12/ and B/sub 6/ deficiencies in an urban population in Karachi, Pakistan

    International Nuclear Information System (INIS)

    Yakub, M.; Iqbal, M.P.; Kakepoto, G.N.; Rafique, G.; Memon, Y.; Azam, I.; Mehboobali, N.; Parveen, S.

    2010-01-01

    To find out the prevalence of hyperhomocysteinemia, and deficiencies of folate, vitamin B6 and vitamin B12 in an urban population in Karachi, Pakistan. Methodology: In a pre and post experimental study, eight hundred and seventy-two apparently healthy adults (aged 18-60 years; 355 males and 517 females) were recruited from a low-income urban locality in East of Karachi from February 2006 to March 2007. Fasting venous blood was obtained. Serum was analyzed for folate and vitamin B12. Plasma was analyzed for pyridoxal phosphate (PLP, co enzymic form of B6) and total homocysteine. A group of vitamin-deficient individuals (n=194) was given 3-week supplementation with folic acid (5mg/ day), methylcobalamin (0.5mg/day) and pyridoxine hydrochloride (vitamin B6, 50 mg/day). After supplementation, serum/plasma levels of folate, vitamin B12, PLP and homocysteine were again determined. Prevalence of hyperhomocysteinemia (>15 mu mol/l) was 32%. Similarly percent values of folate deficiency (<3.5ng/ml), vitamin B6 deficiency (PLP<20 nmol/l) and vitamin B12 deficiency (<200pg/ml) in the study population were 27.5%, 33.7% and 9.74%, respectively. Hyperhomocysteinemia was associated with male sex, folate deficiency, vitamin B12 deficiency [OR (95%CI), 8.3(5.7-12.1); 2.5(1.76-3.58); 2.6(1.5-4.5), respectively]. A 3-week supplementation with folic acid, methylcobalamin and pyridoxine hydrochloride in vitamin deficient subjects decreased plasma homocysteine levels by 37%. High prevalence estimates of folate, vitamin B12, and vitamin B6 deficiencies appear to be the major determinants of hyperhomocysteinemia in a low income general population in Karachi. (author)

  7. Status of B-vitamins and homocysteine in diabetic retinopathy: association with vitamin-B12 deficiency and hyperhomocysteinemia.

    Science.gov (United States)

    Satyanarayana, Alleboena; Balakrishna, Nagalla; Pitla, Sujatha; Reddy, Paduru Yadagiri; Mudili, Sivaprasad; Lopamudra, Pratti; Suryanarayana, Palla; Viswanath, Kalluru; Ayyagari, Radha; Reddy, Geereddy Bhanuprakash

    2011-01-01

    Diabetic retinopathy (DR) is a common cause of blindness. Although many studies have indicated an association between homocysteine and DR, the results so far have been equivocal. Amongst the many determinants of homocysteine, B-vitamin status was shown to be a major confounding factor, yet very little is known about its relationship to DR. In the present study, we, therefore, investigated the status of B-vitamins and homocysteine in DR. A cross-sectional case-control study was conducted with 100 normal control (CN) subjects and 300 subjects with type-2 diabetes (T2D). Of the 300 subjects with T2D, 200 had retinopathy (DR) and 100 did not (DNR). After a complete ophthalmic examination including fundus fluorescein angiography, the clinical profile and the blood levels of all B-vitamins and homocysteine were analyzed. While mean plasma homocysteine levels were found to be higher in T2D patients compared with CN subjects, homocysteine levels were particularly high in the DR group. There were no group differences in the blood levels of vitamins B1 and B2. Although the plasma vitamin-B6 and folic acid levels were significantly lower in the DNR and DR groups compared with the CN group, there were no significant differences between the diabetes groups. Interestingly, plasma vitamin-B12 levels were found to be significantly lower in the diabetes groups compared with the CN group; further, the levels were significantly lower in the DR group compared with the DNR group. Higher homocysteine levels were significantly associated with lower vitamin-B12 and folic acid but not with other B-vitamins. Additionally, hyperhomocysteinemia and vitamin-B12 deficiency did not seem to be related to subjects' age, body mass index, or duration of diabetes. These results thus suggest a possible association between vitamin-B12 deficiency and hyperhomocysteinemia in DR. Further, the data indicate that vitamin-B12 deficiency could be an independent risk factor for DR.

  8. Homocysteine, Cobalamin and Folate Status and their Relations to Neurocognitive and Psychological Markers in Elderly in Northeastern of Iran

    Directory of Open Access Journals (Sweden)

    Lida Manavifar

    2013-06-01

    Full Text Available       Objective(s: Incidence of neurocognitive and psychological disorders may be related to serum homocystein (Hcy, cobalamin (vitamin B12 and folate levels in old people. The aim of this study was to assess the relation between Hcy, cobalamin, folate and neurocognitive and/or psychological disorders in the elderly.   Materials and Methods: In this cross-sectional study, 280 subjects with ≥ 65 years old, were evaluated. The subjects were selected from 12 regions of Mashhad, Iran, over March to October 2009. After blood sampling, data were collected by questionnaire, face to face interview and performing neurocognitive and psychological tests. The sera of 250 persons were analyzed for cobalamin and folate by RIA method. Amongst the aforementioned samples, 78 cases with cobalamin Results: Amongst the people, 126 (45% were male and 154 (55% were female. The prevalence of hyperhomocysteinemia (HHcy was 59.5% and 37.1% in male and female respectively (P -value =0.049. Hcy inversely correlated to cobalamin (r=-0.282, P=0.014 and to folate (r=-0.203, P=0.014. Hcy, cobalamin and folate correlations to neurocognitive and psychological impairments were not statically significant. Conclusion: Hyper Hcy or low cobalamin and folate in the elderly, are prevalent but their relationships with neurocognitive and psychological impairments is controversial. If these relationships had been confirmed, performing a single serum Hcy or cobalamin test would have been enough to diagnose and prevent neurocognitive impairments and inversely, neurocognitive-psychological sign and symptoms could have meant probable tissue vitamin deficiencies. However methods of assessing neurocognitive and psychological markers with validity and reliability of clinical and laboratory tests for finding aforementioned relationships should be revised.  

  9. Homocysteine, Cobalamin and Folate Status and their Relations to Neurocognitive and Psychological Markers in Elderly in Northeasten of Iran.

    Science.gov (United States)

    Manavifar, Lida; Nemati Karimooy, Habibollah; Jamali, Jamshid; Talebi Doluee, Morteza; Shirdel, Abbas; Nejat Shokohi, Amireh; Fatemi Nayyeri, Mahdie

    2013-06-01

    Incidence of neurocognitive and psychological disorders may be related to serum homocystein (Hcy), cobalamin (vitamin B12) and folate levels in old people. The aim of this study was to assess the relation between Hcy, cobalamin, folate and neurocognitive and/or psychological disorders in the elderly. In this cross-sectional study, 280 subjects with ≥ 65 years old ,were evaluated. The subjects were selected from 12 regions of Mashhad, Iran, over March to October 2009. After blood sampling, data were collected by questionnaire, face to face interview and performing neurocognitive and psychological tests. The sera of 250 persons were analyzed for cobalamin and folate by RIA method. Amongst the aforementioned samples, 78 cases with cobalamin <300 pg/ml and folate <6.5 ng/ml were analyzed for Hcy by ELISA method. Amongst the people, 126 (45%) were male and 154 (55%) were female. The prevalence of hyperhomocysteinemia (HHcy) was 59.5% and 37.1% in male and female respectively (P -value =0.049). Hcy inversely correlated to cobalamin (r=-0.282, P=0.014) and to folate (r=-0.203, P=0.014). Hcy, cobalamin and folate correlations to neurocognitive and psychological impairments were not statically significant. Hyper Hcy or low cobalamin and folate in the elderly, are prevalent but their relationships with neurocognitive and psychological impairments is controversial. If these relationships had been confirmed, performing a single serum Hcy or cobalamin test would have been enough enough to diagnose and prevent neurocognitive impairments and inversely, neurocognitive-psychological sign and symptoms could have meant probable tissue vitamin deficiencies. However methods of assessing neurocognitive and psychological markers with validity and reliability of clinical and laboratory tests for finding aforementioned relationships should be revised.

  10. Unexpected high plasma cobalamin

    DEFF Research Database (Denmark)

    Arendt, Johan F B; Nexo, Ebba

    2013-01-01

    It is well-established that more than 8% of patients examined for vitamin B12 deficiency unexpectedly have increased plasma levels of the vitamin, but so far there are no guidelines for the clinical interpretation of such findings. In this review, we summarise known associations between high plasma...... cobalamin binding proteins, transcobalamin and haptocorrin. Based on current knowledge, we suggest a strategy for the clinical interpretation of unexpected high plasma cobalamin. Since a number of the associated diseases are critical and life-threatening, the strategy promotes the concept of 'think...

  11. Cobalamin C Deficiency Shows a Rapidly Progressing Maculopathy With Severe Photoreceptor and Ganglion Cell Loss

    Science.gov (United States)

    Bonafede, Lucas; Ficicioglu, Can H.; Serrano, Leona; Han, Grace; Morgan, Jessica I. W.; Mills, Monte D.; Forbes, Brian J.; Davidson, Stefanie L.; Binenbaum, Gil; Kaplan, Paige B.; Nichols, Charles W.; Verloo, Patrick; Leroy, Bart P.; Maguire, Albert M.; Aleman, Tomas S.

    2015-01-01

    Purpose To describe in detail the retinal structure and function of a group of patients with cobalamin C (cblC) disease. Methods Patients (n = 11, age 4 months to 15 years) with cblC disease (9/11, early onset) diagnosed by newborn screening underwent complete ophthalmic examinations, fundus photography, near-infrared reflectance imaging, and spectral-domain optical coherence tomography (SD-OCT). Electroretinograms (ERGs) were performed in a subset of patients. Results Patients carried homozygous or compound heterozygote mutations in the methylmalonic aciduria and homocystinuria type C (MMACHC) gene. Late-onset patients had a normal exam. All early-onset patients showed a maculopathy; older subjects had a retina-wide degeneration (n = 4; >7 years of age). In general, retinal changes were first observed before 1 year of age and progressed within months to a well-established maculopathy. Pseudocolobomas were documented in three patients. Measurable visual acuities ranged from 20/200 to 20/540. Nystagmus was present in 8/11 patients; 5/6 patients had normal ERGs; 1/6 had reduced rod-mediated responses. Spectral-domain OCT showed macular thinning, with severe ganglion cell layer (GCL) and outer nuclear layer (ONL) loss. Inner retinal thickening was observed in areas of total GCL/ONL loss. A normal lamination pattern in the peripapillary nasal retina was often seen despite severe central and/or retina-wide disease. Conclusions Patients with early-onset cblC and MMACHC mutations showed an early-onset, unusually fast-progressing maculopathy with severe central ONL and GCL loss. An abnormally thickened inner retina supports a remodeling response to both photoreceptor and ganglion cell degeneration and/or an interference with normal development in early-onset cblC. PMID:26658511

  12. 4-ethylphenyl-cobalamin impairs tissue uptake of vitamin B12 and causes vitamin B12 deficiency in mice

    DEFF Research Database (Denmark)

    Mutti, Elena; Ruetz, Markus; Birn, Henrik

    2013-01-01

    Coβ-4-ethylphenyl-cob(III) alamin (EtPhCbl) is an organometallic analogue of vitamin B12 (CNCbl) which binds to transcobalamin (TC), a plasma protein that facilitates the cellular uptake of cobalamin (Cbl). In vitro assays with key enzymes do not convert EtPhCbl to the active coenzyme forms of Cbl...... treated with EtPhCbl (1.01±0.12 µmol/L) compared to controls (0.30±0.02 µmol/L) and CNCbl (0.29±0.01 µmol/L) treated animals. The same pattern was observed for tHcy. Plasma total Cbl concentration was higher in animals treated with EtPhCbl (128.82±1.87 nmol/L) than in CNCbl treated animals (87.......64±0.93 nmol/L). However, the organ levels of total Cbl were significantly lower in animals treated with EtPhCbl compared to CNCbl treated animals or controls, notably in the liver (157.07±8.56 pmol/g vs. 603.85±20.02 pmol/g, and 443.09±12.32 pmol/g, respectively). Differences between the three groups...

  13. Cobalamin analogues in humans

    DEFF Research Database (Denmark)

    Hardlei, Tore Forsingdal; Obeid, Rima; Herrmann, Wolfgang

    2013-01-01

    BACKGROUND: Haptocorrin (HC) carries cobalamin analogues (CorA), but whether CorA are produced in the body is unknown. All cobalamins (Cbl) to the foetus are delivered by the Cbl-specific protein transcobalamin (TC), and therefore analysis of cord serum for CorA may help to clarify the origin...

  14. Effect of two different sublingual dosages of vitamin B12 on cobalamin nutritional status in vegans and vegetarians with a marginal deficiency: A randomized controlled trial.

    Science.gov (United States)

    Del Bo', Cristian; Riso, Patrizia; Gardana, Claudio; Brusamolino, Antonella; Battezzati, Alberto; Ciappellano, Salvatore

    2018-02-15

    Vegetarians and vegans are more vulnerable to vitamin B 12 deficiency with severe risks of megaloblastic anemia, cognitive decline, neuropathy, and depression. An easy and simple method of supplementation consists of taking one weekly dosage of 2000 μg. However, single large oral doses of vitamin B 12 are poorly absorbed. The present research evaluates the ability of two different sublingual dosages of vitamin B 12 (350 μg/week vs 2000 μg/week) in improving cyanocobalamin (vitamin B 12 ) nutritional status in vegans and vegetarians with a marginal deficiency. A 12-week randomized, double-blind, controlled, parallel intervention trial was performed. Forty subjects with marginal vitamin B 12 deficiency were enrolled and randomly divided into two groups: test group Ld (low dose, 350 μg/week) and control group Hd (high dose, 2000 μg/week) vitamin B 12 supplementation. Blood samples were collected at baseline and after 15, 30, 60, and 90 days from the intervention for the determination of vitamin B 12 , related metabolic markers, and blood cell counts. Two-way analysis of variance showed a significant effect of time (P < 0.0001) and of time × treatment interaction (P = 0.012) on serum concentration of vitamin B 12 that increased after 90-day supplementation (Ld and Hd) compared to baseline. Both the supplements increased (P < 0.0001, time effect) the levels of holotranscobalamin, succinic acid, methionine and wellness parameter, while decreased (P < 0.0001, time effect) the levels of methylmalonic acid, homocysteine and folate compared to baseline. No difference was observed between groups (LdvsHd). No effect was detected for vitamin B 6 and blood cell count. In our experimental conditions, both supplements were able to restore adequate serum concentrations of vitamin B 12 and to improve the levels of related metabolic blood markers in subjects with a marginal deficiency. The results support the use of a sublingual dosage of 50 μg/day (350

  15. Hyperhomocysteinemia in Recurrent Miscarriage

    International Nuclear Information System (INIS)

    Gaber, Kh.R.; Farag, M.K.; Soliman, S.Et.; Abd Al-Kaderm, M.A.

    2008-01-01

    Objective: An elevated total plasma homocysteine level has been suggested as a possible risk factor in women suffering from recurrent pregnancy loss. The current study was undertaken to assess the association between homocysteine, folate, cobalamin (vitamin B12) and the risk of recurrent pregnancy loss. Design: Case . control study Materials and Methods: The study included 57 non-pregnant Egyptian women. They were classified according to their obstetric history into 2 groups: 32 cases with at least two consecutive miscarriages (Study group), and 25 cases with normal obstetric history (Control group). All cases were tested for plasma total homocysteine, serum folate and cobalamin (vitamin B12). Results: The fasting total homocysteine was significantly higher in the study group as compared to the control group. While the median concentrations for the vitamins studied were significantly lower in women of the study group as compared to the controls. Elevated homocysteine and reduced vitamin B12 can be considered risk factors for recurrent miscarriage with odds ratio (OR) and 95% confidence intervals (95% CI) of 1.839 (1.286, 2.63) and 1.993 (1.346, 2.951) respectively in the group of recurrent miscarriages. The OR (95% CI) in the study population for low serum folate concentrations was 1.23 (0.776, 2.256). Conclusion: Elevated homocysteine and reduced serum vitamin B12 are risk factors for recurrent miscarriage. Low serum folate did not seem a risk factor for recurrent miscarriage. Testing for homocysteine levels in women suffering from unexplained recurrent miscarriage and pre-conceptional supplementation with vitamin B12 might be beneficial to improve pregnancy outcome

  16. Hyperhomocysteinemia in Recurrent Miscarriage

    Energy Technology Data Exchange (ETDEWEB)

    Gaber, Kh R; Farag, M K [Prenatal Diagnosis and Fetal Medicine Department, National Research Centre, Dokki, Giza (Egypt); Soliman, S Et [Radioisotope Department, Nuclear Research Centre, Atomic Energy Authority, Cairo (Egypt); Abd Al-Kaderm, M A [Obstetrics and Gynecology Department, Faculty of Medicine, Cairo University, Cairo (Egypt)

    2008-07-01

    Objective: An elevated total plasma homocysteine level has been suggested as a possible risk factor in women suffering from recurrent pregnancy loss. The current study was undertaken to assess the association between homocysteine, folate, cobalamin (vitamin B12) and the risk of recurrent pregnancy loss. Design: Case . control study Materials and Methods: The study included 57 non-pregnant Egyptian women. They were classified according to their obstetric history into 2 groups: 32 cases with at least two consecutive miscarriages (Study group), and 25 cases with normal obstetric history (Control group). All cases were tested for plasma total homocysteine, serum folate and cobalamin (vitamin B12). Results: The fasting total homocysteine was significantly higher in the study group as compared to the control group. While the median concentrations for the vitamins studied were significantly lower in women of the study group as compared to the controls. Elevated homocysteine and reduced vitamin B12 can be considered risk factors for recurrent miscarriage with odds ratio (OR) and 95% confidence intervals (95% CI) of 1.839 (1.286, 2.63) and 1.993 (1.346, 2.951) respectively in the group of recurrent miscarriages. The OR (95% CI) in the study population for low serum folate concentrations was 1.23 (0.776, 2.256). Conclusion: Elevated homocysteine and reduced serum vitamin B12 are risk factors for recurrent miscarriage. Low serum folate did not seem a risk factor for recurrent miscarriage. Testing for homocysteine levels in women suffering from unexplained recurrent miscarriage and pre-conceptional supplementation with vitamin B12 might be beneficial to improve pregnancy outcome.

  17. Cobalamin inactivation by nitrous oxide produces severe neurological impairment in fruit bats: protection by methionine and aggravation by folates

    Energy Technology Data Exchange (ETDEWEB)

    van der Westhuyzen, J.; Fernandes-Costa, F.; Metz, J.

    1982-11-01

    Nitrous oxide, which inactivates cobalamin when administered to fruit bats, results in severe neurological impairment leading to ataxia, paralysis and death. This occurs after about 6 weeks in animals depleted of cobalamin by dietary restriction, and after about 10 weeks in cobalamin replete bats. Supplementation of the diet with pteroylglutamic acid caused acceleration of the neurological impairment--the first unequivocal demonstration of aggravation of the neurological lesion in cobalamin deficiency by pteroylglutamic acid. The administration of formyltetrahydropteroylglutamic acid produced similar aggravation of the neurological lesion. Supplementation of the diet with methionine protected the bats from neurological impairment, but failed to prevent death. Methionine supplementation protected against the exacerbating effect of folate, preventing the development of neurological changes. These findings lend support to the hypothesis that the neurological lesion in cobalamin deficiency may be related to a deficiency in the methyl donor S-adenosylmethionine which follows diminished synthesis of methionine.

  18. Hyperhomocysteinemia in chronic alcoholism: A case with retinal manifestations.

    Science.gov (United States)

    Palmero-Fernández, L; Fernández-Treguerres, F; Santos-Bueso, E; Sáenz-Francés, F; Martínez-de-la-Casa, J M; García-Feijóo, J; García-Sánchez, J

    2014-08-01

    An alcoholic patient with loss of vision in his right eye and a peripapillar haemorrhage, who then presented with a venous thrombosis. Blood analysis revealed hyperhomocysteinemia with coagulation parameters within the normal range. In the follow-up he developed a bilateral optic neuropathy. An increase in homocysteine levels is common in alcoholics, and it has been considered a vascular risk factor. Folic acid and vitamins B6 and B12 deficiency may lead to hyperhomocysteinemia, as they participate in its metabolism. When presented with a retinal occlusive disease or ischemic optic neuropathy in young patients, coagulation disorders and elevated levels of homocysteine should be ruled out. Copyright © 2013 Sociedad Española de Oftalmología. Published by Elsevier Espana. All rights reserved.

  19. Cobalamin and haptocorrin in human milk and cobalamin-related variables in mother and child

    DEFF Research Database (Denmark)

    Greibe, Eva; Lildballe, Dorte L; við Streym, Susanna

    2013-01-01

    BACKGROUND: Measurement of milk cobalamin is hampered by the high content of the cobalamin-binding protein haptocorrin, and limited data are available relating trustworthy measures of milk cobalamin to cobalamin status in healthy mothers and their children. OBJECTIVES: The objectives were to expl...

  20. Nutritional Intake and Status of Cobalamin and Folate among Non-Pregnant Women of Reproductive Age in Bhaktapur, Nepal

    Directory of Open Access Journals (Sweden)

    Ram K. Chandyo

    2016-06-01

    Full Text Available Cobalamin and folate are especially important for women of childbearing age due to their ubiquitous role in fetal growth and development. Population-based data on cobalamin and folate status are lacking from Nepal, where diets are mostly vegetarian. The objectives of the study were to investigate cobalamin and folate intake and status, and to explore associations with socio-demographics, anthropometrics, anemia, and dietary habits. Following a random selection of geographical clusters, we collected blood samples from 500 non-pregnant women and 24-h dietary recalls and food frequency questionnaires from a subsample of 379 women. Twenty percent of the women did not consume any food containing cobalamin during the days recalled, and in 72% nutritional cobalamin intake was <1 μg/day. Eighty-four percent of the women had cobalamin intake lower than the estimated average requirement (EAR (<2 μg/day. In contrast, only 12% of the women had a folate intake less than 100 μg per day, whereas 62% had intake between 100 and 320 μg. Low plasma cobalamin (<150 pmol/L was found in 42% of the women, most of whom (88% also had elevated levels of methylmalonic acid. Our results indicated a high prevalence of nutritional cobalamin deficiency, while folate deficiency was uncommon.

  1. Failure to thrive and life-threatening complications due to inherited selective cobalamin malabsorption effectively managed in a juvenile Australian shepherd dog

    Science.gov (United States)

    Gold, Ashley J.; Scott, Michael A.; Fyfe, John C.

    2015-01-01

    A juvenile Australian shepherd dog exhibited failure to grow, inappetence, weakness, nonregenerative anemia, neutropenia, and cobalamin deficiency. DNA testing confirmed homozygosity of an amnionless mutation (AMN c.3G > A). Clinical signs resolved with supportive care and parenteral cobalamin supplementation. Inherited selective intestinal cobalamin malabsorption requiring lifelong parenteral supplementation should be considered in Australian shepherds, giant schnauzers, border collies, and beagles that fail to thrive. PMID:26483576

  2. Leg ulcers due to hyperhomocysteinemia

    Directory of Open Access Journals (Sweden)

    Krupa Shankar D

    2006-01-01

    Full Text Available Chronic leg ulcers are rare in young adults and generally indicate a vascular cause. We report a case of a 26-year-old man with leg ulcers of eight months duration. Doppler study indicated venous incompetence and a postphlebitic limb. However, as the distribution and number of ulcers was not consistent with stasis alone and no features of collagen vascular disease were noted, a hyperviscosity state was considered and confirmed with significantly elevated homocysteine level in the serum. Administration of vitamins B1, B2, B6 and B12, trimethyl-glycine, mecobalamine, folic acid and povidone iodine dressings with culture-directed antibiotic therapy led to a satisfactory healing of ulcers over a period of one month. Hyperhomocysteinemia must be considered in the differential diagnosis of leg ulcers in young individuals.

  3. Cobalamin and folate status predicts mental development scores in North Indian children 12-18 mo of age.

    Science.gov (United States)

    Strand, Tor A; Taneja, Sunita; Ueland, Per M; Refsum, Helga; Bahl, Rajiv; Schneede, Joern; Sommerfelt, Halvor; Bhandari, Nita

    2013-02-01

    Micronutrient deficiencies can affect cognitive function. Many young children in low- and middle-income countries have inadequate cobalamin (vitamin B-12) status. The objective was to measure the association of plasma concentrations of folate, cobalamin, total homocysteine, and methylmalonic acid with cognitive performance at 2 occasions, 4 mo apart, in North Indian children aged 12-18 mo. Bayley Scales of Infant Development II were used to assess cognition. In multiple regression models adjusted for several potential confounders, we measured the association between biomarkers for folate and cobalamin status and psychomotor or mental development scores on the day of blood sampling and 4 mo thereafter. Each 2-fold increment in plasma cobalamin concentration was associated with a significant increment in the mental development index score of 1.3 (95% CI: 0.2, 2.4; P = 0.021). Furthermore, each 2-fold increment in homocysteine or methylmalonic acid concentration was associated with a decrement in mental development index score of 2.0 (95% CI: 0.5, 3.4; P = 0.007) or 1.1 (95% CI: 0.3, 1.8; P = 0.004) points, respectively. Plasma folate concentration was significantly and independently associated with mental development index scores only when children with poor cobalamin status were excluded, ie, in those who had cobalamin concentrations below the 25th percentile. None of these markers was associated with psychomotor scores in the multiple regression models. Cobalamin and folate status showed a statistically significant association with cognitive performance. Given the high prevalence of deficiencies in these nutrients, folate and cobalamin supplementation trials are required to measure any beneficial effect on cognition.

  4. Cobalamin and its binding protein in rat milk

    DEFF Research Database (Denmark)

    Raaberg, Lasse; Nexø, Ebba; Poulsen, Steen Seier

    1989-01-01

    Cobalamin and its binding protein, haptocorrin, are present in rat milk throughout the lactation period. The concentration of cobalamin is approximately 0.3-times the concentration of the unsaturated binding protein. The concentration of the unsaturated cobalamin-binding protein varies between 18...

  5. Metformin Lowers Serum Cobalamin without Changing Other Markers of Cobalamin Status: A Study on Women with Polycystic Ovary Syndrome

    DEFF Research Database (Denmark)

    Greibe, Eva; Trolle, G. Birgitta; Bor, Mustafa Vakur

    2013-01-01

    Treatment with the anti-diabetic drug metformin is followed by a decline in plasma cobalamin, but it is unsettled whether this denotes an impaired cobalamin status. This study has explored changes in the markers of cobalamin status in women with Polycystic Ovary Syndrome treated with metformin (1...

  6. Metformin Lowers Serum Cobalamin without Changing Other Markers of Cobalamin Status: A Study on Women with Polycystic Ovary Syndrome

    Directory of Open Access Journals (Sweden)

    Ebba Nexo

    2013-07-01

    Full Text Available Treatment with the anti-diabetic drug metformin is followed by a decline in plasma cobalamin, but it is unsettled whether this denotes an impaired cobalamin status. This study has explored changes in the markers of cobalamin status in women with Polycystic Ovary Syndrome treated with metformin (1.5–2.5 g per day (n = 29 or placebo (n = 23 for six months. Serum samples were collected before and after two, four, and six months of treatment. We found serum cobalamin to decline and reach significant lower levels after six months of treatment (p = 0.003. Despite the decline in serum cobalamin, we observed no reductions in the physiological active part of cobalamin bound to transcobalamin (holotranscobalamin, or increase in the metabolic marker of cobalamin status, methylmalonic acid. Instead, the non-functional part of circulating cobalamin bound to haptocorrin declined (p = 0.0009. Our results have two implications: The data questions whether metformin treatment induces an impaired cobalamin status in PCOS patients, and further suggests that serum cobalamin is a futile marker for judging cobalamin status in metformin-treated patients.

  7. Naturally occurring cobalamins have antimalarial activity.

    Science.gov (United States)

    Chemaly, Susan M; Chen, Chien-Teng; van Zyl, Robyn L

    2007-05-01

    The acquisition of resistance by malaria parasites towards existing antimalarials has necessitated the development of new chemotherapeutic agents. The effect of vitamin B(12) derivatives on the formation of beta-haematin (synthetic haemozoin) was determined under conditions similar to those in the parasitic food vacuole (using chloroquine, a known inhibitor of haemozoin formation for comparison). Adenosylcobalamin (Ado-cbl), methylcobalamin (CH(3)-cbl) and aquocobalamin (H(2)O-cbl) were approximately forty times more effective inhibitors of beta-haematin formation than chloroquine, cyanocobalamin (CN-cbl) was slightly more inhibitory than chloroquine, while dicyanocobinamide had no effect. It is proposed that the cobalamins exert their inhibitory effect on beta-haematin formation by pi-interactions of their corrin ring with the Fe(III)-protoporphyrin ring and by hydrogen-bonding using their 5,6-dimethylbenzimidazole/ribose/sugar side-chain. The antimalarial activity for the cobalamins (Ado-cbl>CH(3)-cbl>H(2)O-cbl>CN-cbl) was found to be less than that for chloroquine or quinine. Ado-cbl, CH(3)-cbl and CN-cbl do not accumulate in the parasite food vacuole by pH trapping, but H(2)O-cbl does. Unlike humans, the malaria parasite has only one enzyme that uses cobalamin as a cofactor, namely methionine synthase, which is important for growth and metabolism. Thus cobalamins in very small amounts are necessary for Plasmodium falciparum growth but in larger amounts they display antimalarial properties.

  8. The active site of oxidative phosphorylation and the origin of hyperhomocysteinemia in aging and dementia.

    Science.gov (United States)

    McCully, Kilmer S

    2015-01-01

    The active site of oxidative phosphorylation and adenosine triphosphate (ATP) synthesis in mitochondria is proposed to consist of two molecules of thioretinamide bound to cobalamin, forming thioretinaco, complexed with ozone, oxygen, nicotinamide adenine dinucleotide. and inorganic phosphate, TR2CoO3O2NAD(+)H2PO4(-). Reduction of the pyridinium nitrogen of the nicotinamide group by an electron from electron transport complexes initiates polymerization of phosphate with adenosine diphosphate, yielding nicotinamide riboside and ATP bound to thioretinaco ozonide oxygen. A second electron reduces oxygen to hydroperoxyl radical, releasing ATP from the active site. A proton gradient is created within F1F0 ATPase complexes of mitochondria by reaction of protons with reduced nicotinamide riboside and with hydroperoxyl radical, yielding reduced nicotinamide riboside and hydroperoxide. The hyperhomocysteinemia of aging and dementia is attributed to decreased synthesis of adenosyl methionine by thioretinaco ozonide and ATP, causing decreased allosteric activation of cystathionine synthase and decreased allosteric inhibition of methylenetetrahydrofolate reductase and resulting in dysregulation of methionine metabolism. © 2015 by the Association of Clinical Scientists, Inc.

  9. Oral versus intramuscular cobalamin treatment in megaloblastic anemia: a single-center, prospective, randomized, open-label study.

    Science.gov (United States)

    Bolaman, Zahit; Kadikoylu, Gurhan; Yukselen, Vahit; Yavasoglu, Irfan; Barutca, Sabri; Senturk, Taskin

    2003-12-01

    Cobalamin (vitamin B12) deficiency, the most common cause of megaloblastic anemia, is treated with intramuscular (IM) cobalamin. It has been suggested by some investigators that oral (p.o.) cobalamin treatment may be as effective in the treatment of this condition, with the advantages of ease of administration and lower cost. This study assessed the effects and cost of p.o. versus i.m. cobalamin treatment in patients with megaloblastic anemia due to cobalamin deficiency. This was a 90-day, prospective, randomized, open-label study conducted at the Division of Hematology, Department of Internal Medicine, Adnan Menderes University Research and Practice Hospital (Aydin, Turkey). Patients aged > or =16 years with megaloblastic anemia due to cobalamin deficiency were randomized to receive 1000-microg cobalamin p.o. once daily for 10 days (p.o. group) or 1000-microg cobalamin i.m. once daily for 10 days (i.m. group). After 10 days, both treatments were administered once a week for 4 weeks, and after that, once a month for life. Patients were assessed for the presence of reticulocytosis between treatment days 5 and 10 until it was detected. Therapeutic effectiveness was assessed by measuring hematologic parameters on days 0, 10, 30, and 90 and serum vitamin B12 concentration on days 0 and 90. The Mini-Mental State Examination was used before and after the B12 therapy for cognitive function assessment and 125-Hz diapozone was used for vibration threshold testing. Neurologic sensory assessment, including soft-touch and pinprick examinations, was used to identify neuropathy at baseline and study end. Tolerability was assessed using laboratory tests and patient interview. Cost was assessed using the cost of the study drug and of the injection. Sixty patients completed the study 26 in the p.o. group (16 men, 10 women; mean [SD] age, 60 [15] years) and 34 in the i.m. group (17 men, 17 women; mean [SD] age, 64 [10] years). Reticulocytosis was observed in all patients. In the p

  10. Oral cobalamin supplementation in cats with hypocobalaminaemia: a retrospective study.

    Science.gov (United States)

    Toresson, Linda; Steiner, Joerg M; Olmedal, Gunilla; Larsen, MajBritt; Suchodolski, Jan S; Spillmann, Thomas

    2017-12-01

    Objectives The objective of the study was to evaluate whether oral cobalamin supplementation can restore normocobal-aminaemia in cats with hypocobalaminaemia and clinical signs of gastrointestinal disease. Methods This was a retrospective study based on a computerised database search for client-owned cats treated at Evidensia Specialist Animal Hospital, Helsingborg, Sweden, during the period December 2013 to August 2016. Inclusion criteria were cats with clinical signs of chronic enteropathy, an initial serum cobalamin concentration ⩽250 pmol/l (reference interval 214-738 pmol/l) and oral treatment with cobalamin tablets. Results Twenty-five cats met the inclusion criteria. The cats were treated with 0.25 mg cyanocobalamin tablets once daily. Serum cobalamin concentration was rechecked 27-94 days after continuous oral cobalamin supplementation. All cats had serum cobalamin concentrations above the reference interval after oral cobalamin supplementation. Median (range) serum cobalamin concentration was 128 pmol/l (111-250 pmol/l) prior to treatment and 2701 pmol/l (738-16,359 pmol/l) after supplementation. This difference was statistically significant ( P cats with hypocobalaminaemia. Thus, oral cobalamin supplementation is a promising alternative to parenteral administration. Prospective comparative studies in cats being treated with parenteral vs oral cobalamin supplementation in a larger number of patients are warranted before oral supplementation can be recommended for routine use.

  11. Transcellular transport of cobalamin in aortic endothelial cells.

    Science.gov (United States)

    Hannibal, Luciana; Bolisetty, Keerthana; Axhemi, Armend; DiBello, Patricia M; Quadros, Edward V; Fedosov, Sergey; Jacobsen, Donald W

    2018-05-09

    Cobalamin [Cbl (or B 12 )] deficiency causes megaloblastic anemia and a variety of neuropathies. However, homeostatic mechanisms of cyanocobalamin (CNCbl) and other Cbls by vascular endothelial cells are poorly understood. Herein, we describe our investigation into whether cultured bovine aortic endothelial cells (BAECs) perform transcytosis of B 12 , namely, the complex formed between serum transcobalamin and B 12 , designated as holo-transcobalamin (holo-TC). We show that cultured BAECs endocytose [ 57 Co]-CNCbl-TC (source material) via the CD320 receptor. The bound Cbl is transported across the cell both via exocytosis in its free form, [ 57 Co]-CNCbl, and via transcytosis as [ 57 Co]-CNCbl-TC. Transcellular mobilization of Cbl occurred in a bidirectional manner. A portion of the endocytosed [ 57 Co]-CNCbl was enzymatically processed by methylmalonic aciduria combined with homocystinuria type C (cblC) with subsequent formation of hydroxocobalamin, methylcobalamin, and adenosylcobalamin, which were also transported across the cell in a bidirectional manner. This demonstrates that transport mechanisms for Cbl in vascular endothelial cells do not discriminate between various β-axial ligands of the vitamin. Competition studies with apoprotein- and holo-TC and holo-intrinsic factor showed that only holo-TC was effective at inhibiting transcellular transport of Cbl. Incubation of BAECs with a blocking antibody against the extracellular domain of the CD320 receptor inhibited uptake and transcytosis by ∼40%. This study reveals that endothelial cells recycle uncommitted intracellular Cbl for downstream usage by other cell types and suggests that the endothelium is self-sufficient for the specific acquisition and subsequent distribution of circulating B 12 via the CD320 receptor. We posit that the endothelial lining of the vasculature is an essential component for the maintenance of serum-tissue homeostasis of B 12 .-Hannibal, L., Bolisetty, K., Axhemi, A., DiBello, P

  12. Acute myocardial infarction and pulmonary embolism in a young man with pernicious anemia-induced severe hyperhomocysteinemia

    Directory of Open Access Journals (Sweden)

    Hofmann Marion A

    2009-05-01

    Full Text Available Abstract A 27 year-old man who presented to the hospital with progressive lower extremity weakness, developed an acute ST elevation myocardial infarction on his second hospital day. Primary angioplasty to the left anterior descending coronary artery was performed. Due to persistent dyspnea, the patient underwent a diagnostic chest computed tomography which confirmed multiple small pulmonary emboli. Laboratory analysis revealed a megaloblastic anemia with a reduced vitamin B12 level and positive titers for antibodies against intrinsic factor, establishing a diagnosis of pernicious anemia. Screening for hypercoaguable markers documented an isolated severely elevated homocysteine levels (105 μmol/l. No other significant risk factors for coronary artery disease including a family history of premature atherosclerosis were identified. This case illustrates the importance of testing for hyperhomocysteinemia as part of a workup for atherothrombotic disease, especially in patients without other significant risk factors. The severity of hyperhomocysteinemia found in our patient is unusual for patients with vitamin B12 malabsorption and raises the question of whether the widely practiced folic acid fortification in the United States may mask or even worsen vitamin B12 deficiency over time, leading to more severe cases of vitamin B12 deficiency and hyperhomocysteinemia than seen in the past.

  13. Vitamin-responsive disorders: cobalamin, folate, biotin, vitamins B1 and E.

    Science.gov (United States)

    Baumgartner, Matthias R

    2013-01-01

    The catalytic properties of many enzymes depend on the participation of vitamins as obligatory cofactors. Vitamin B12 (cobalamin) and folic acid (folate) deficiencies in infants and children classically present with megaloblastic anemia and are often accompanied by neurological signs. A number of rare inborn errors of cobalamin and folate absorption, transport, cellular uptake, and intracellular metabolism have been delineated and identification of disease-causing mutations has improved our ability to diagnose and treat many of these conditions. Two inherited defects in biotin metabolism are known, holocarboxylase synthetase and biotinidase deficiency. Both lead to multiple carboxylase deficiency manifesting with metabolic acidosis, neurological abnormalities, and skin rash. Thiamine-responsive megaloblastic anemia is characterized by megaloblastic anemia, non-type I diabetes, and sensorineural deafness that responds to pharmacological doses of thiamine (vitamin B1). Individuals affected with inherited vitamin E deficiencies including ataxia with isolated vitamin E deficiency and abetalipoproteinemia present with a spinocerebellar syndrome similar to patients with Friedreich's ataxia. If started early, treatment of these defects by oral or parenteral administration of the relevant vitamin often results in correction of the metabolic defect and reversal of the signs of disease, stressing the importance of early and correct diagnosis in these treatable conditions. Copyright © 2013 Elsevier B.V. All rights reserved.

  14. Vitamin B12 deficiency

    Science.gov (United States)

    Vitamin B12 (B12; also known as cobalamin) is a B vitamin that has an important role in cellular metabolism, especially in DNA synthesis, methylation and mitochondrial metabolism. Clinical B12 deficiency with classic haematological and neurological manifestations is relatively uncommon. However, sub...

  15. The Cobalamin-binding Protein in Zebrafish is an Intermediate Between the Three Cobalamin-binding Proteins in Human

    DEFF Research Database (Denmark)

    Greibe, Eva Holm; Fedosov, Sergey; Nexø, Ebba

    2012-01-01

    are the oldest evolutionary derivatives followed by IF and HC (the latter being present only in reptiles and most but not all mammals). Our findings suggest that the only cobalamin-binding protein in zebrafish is an intermediate between the three human cobalamin binders. These findings support the hypothesis...

  16. Common micronutrient deficiencies among food aid beneficiaries ...

    African Journals Online (AJOL)

    Results: Vitamin A and iron deficiencies were the most prevalent micronutrient deficiencies among food aid beneficiaries. Other probable deficiencies prevailing were zinc, vitamins thiamine, riboflavin, niacin folate, cyano-cobalamine, ascorbic acid vitamin D and calcium because of the low intake of dairy products and meat.

  17. 89Zr-Cobalamin PET Tracer

    DEFF Research Database (Denmark)

    Kuda-Wedagedara, Akhila N W; Workinger, Jayme L; Nexo, Ebba

    2017-01-01

    Vitamin B12, or cobalamin (Cbl), is an essential nutrient. Acquisition, transport, and cellular internalization of Cbl are dependent on specific binding proteins and associated receptors. The circulating transport protein transcobalamin (TC) promotes cellular uptake via binding to specific......-Cbl (CN-Cbl). In vitro studies employing the CD320 receptor-positive breast cancer cell line MDA-MB-453 showed a 6- to 10-fold greater uptake of 89Zr-Cbl when compared with the uptake in the presence of 200-fold excess of CN-Cbl at 37 °C. We used nude mice with MDA-MB-453 tumors to study the feasibility...

  18. Cobalamins uncovered by modern electronic structure calculations

    DEFF Research Database (Denmark)

    Kepp, Kasper Planeta; Ryde, Ulf

    2009-01-01

    electronic-structure calculations, in particular density functional methods, the understanding of the molecular mechanism of cobalamins has changed dramatically, going from a dominating view of trans-steric strain effects to a much more complex view involving an arsenal of catalytic strategies. Among...... these are cis-steric distortions, electrostatic stabilization of radical products, the realization that nucleotide units can serve as polar handles, and the careful design of the active sites, with polar residues in the radical enzymes and non-polar residues in the transferases. Together, these strategies...

  19. Isolated abducens nerve palsy with hyperhomocysteinemia: Association and outcomes

    Directory of Open Access Journals (Sweden)

    Virender Sachdeva

    2013-01-01

    Full Text Available Ischemic abducens nerve palsy usually presents as isolated cranial nerve palsy in the middle aged and elderly patients with known risk factors such as diabetes mellitus, hypertension, dyslipidemia, carotid artery disease, etc., In this report, we describe four patients with isolated abducens nerve palsy who presented with an acute onset diplopia whose detailed history and examination were suggestive of an ischemic etiology. Detailed systemic and laboratory evaluation revealed hyperhomocysteinemia as the only potential risk factor. To the best of our knowledge this is the first report of association of hyperhomocysteinemia and isolated abducens nerve palsy.

  20. Three family members with elevated plasma cobalamin, transcobalamin and soluble transcobalamin receptor (sCD320)

    DEFF Research Database (Denmark)

    Hoffmann-Lücke, Elke; Arendt, Johan F B; Nissen, Peter H

    2013-01-01

    deficiency were found. DNA sequencing of the TCN2 gene revealed several known polymorphisms not associated with highly elevated transcobalamin levels. Upon gel filtration, sCD320 eluted as a larger molecule than previously reported. By incubation with anti-transcobalamin antibodies, we precipitated both...... transcobalamin and part of sCD320. CONCLUSIONS: The high cobalamin levels were mainly explained by high levels of holoTC, possibly caused by complex formation with its soluble receptor, sCD320. The family occurrence points to a genetic explanation....

  1. Enzymatic extraction of cobalamin from monoclonal antibody captured haptocorrin and transcobalamin

    DEFF Research Database (Denmark)

    Hardlei, Tore Forsingdal; Mørkbak, Anne Louise; Nexo, Ebba

    2007-01-01

    OBJECTIVES: Current extraction methods for cobalamins from serum influence the molecular characteristics of the vitamin. Therefore, an extraction procedure that leaves the cobalamins unchanged is needed. DESIGN AND METHODS: Monoclonal antibodies towards transcobalamin (TC) and haptocorrin (HC) (in...

  2. Spinal cord demyelination combined with hyperhomocysteinemia: a case report

    Directory of Open Access Journals (Sweden)

    Hao MM

    2014-11-01

    Full Text Available Meimei Hao, Yan Zhang, Shuangxing Hou, Yanling Chen, Ming Shi, Gang Zhao, Yanchun Deng Department of Neurology, Xijing Hospital, Fourth Military Medical University, Xi’an, People’s Republic of China Abstract: Hyperhomocysteinemia (HHcy has been recognized as an independent risk factor for atherosclerotic vascular disease. Here we report a patient who suffered from spinal cord demyelination combined with HHcy. The patient was admitted to our hospital with a diagnosis of acute myelitis. However, hormone therapy was ineffective. Further investigations revealed that he had HHcy and a homozygous mutation of the gene encoding methylenetetrahydrofolate reductase (MTHFR c.677C>T, which is a key enzyme involved in homocysteine metabolism. In view of these findings, we treated the patient with B vitamins and his symptoms gradually improved. Spinal magnetic resonance imaging performed 3 months after onset showed near recovery of the lesion. To our knowledge, similar reports are rare. Keywords: demyelination, hyperhomocysteinemia, homocysteine, methylenetetrahydrofolate reductase, methylation

  3. Hyperhomocysteinemia and the role of B vitamins in cancer

    International Nuclear Information System (INIS)

    Plazar, Nadja; Jurdana, Mihaela

    2010-01-01

    Patients suffering from malignancies have increased complications due to corresponding cardiovascular diseases and risk factor for the development of venous thromboembolism. Epidemiological studies have shown that increased homocysteine plasma concentration (hyperhomocysteinemia) is related to a higher risk of coronary heart disease, stroke, peripheral vascular disease and malignancies. Homocysteine (tHcy) is an intermediate sulfur-containing amino acid produced from methionine during processing of dietary proteins. The plasma homocysteine levels are strongly influenced by diet, as well as by genetic factors. Folic acid, vitamins B6 and B12 are dietary components which influence the plasma homocysteine levels the most. Several studies have found that high blood levels of B vitamins are related to the integrity and function of DNA, and, are at least related to lower concentration of homocysteine. Folate depletion has been found to change DNA methylation and DNA synthesis in both animal and human studies. Because of this critical role of folate, most studies including homocysteine have focused on these two actions. Hyperhomocysteinemia proves to be the most common condition highly associated with both venous and arterial thrombosis in many cancer patients, while the associated pathophysiology has not been precisely established yet. Therefore, of current interest is the possible role of folate metabolism developing into a cancer initiating hyperhomocysteinemia. This review will discuss this possibility

  4. A Single Rainbow Trout Cobalamin-binding Protein Stands in for Three Human Binders

    DEFF Research Database (Denmark)

    Greibe, Eva Holm; Fedosov, Sergey; Sorensen, Boe S

    2012-01-01

    affinity for the cobalamin analog cobinamide. Like haptocorrin and transcobalamin, the trout cobalamin-binding protein was present in plasma and recognized ligands with altered nucleotide moiety. Like intrinsic factors, the trout cobalamin-binding protein was present in the stomach and resisted degradation...... by trypsin and chymotrypsin. It also resembled intrinsic factor in the composition of conserved residues in the primary cobalamin-binding site in the C terminus. The trout cobalamin-binding protein was glycosylated and displayed spectral properties comparable with those of haptocorrin and intrinsic factor...

  5. The biomarker-based validity of a food frequency questionnaire to assess the intake status of folate, pyridoxine and cobalamin among Iranian primary breast cancer patients.

    Science.gov (United States)

    Pirouzpanah, S; Taleban, F-A; Mehdipour, P; Atri, M; Hooshyareh-rad, A; Sabour, S

    2014-03-01

    Folate, pyridoxine and cobalamin are coenzymatically essential in one-carbon methyl metabolism, and their deficiencies could explain some alterations during breast carcinogenesis. We aimed to evaluate the validity of folate, pyridoxine and cobalamin estimates from a food frequency questionnaire (FFQ) on the basis of their corresponding fasting plasma biomarkers, in breast cancer (BC) patients. In a prospective, consecutive case series, 149 women with primary BC aged between 30 and 69 years as a representative sample of Iranian women with BC were recruited. The 136-item FFQ was used for the validity assay. Fasting plasma folate and cobalamin were tested by automated electrochemiluminescence. The high-pressure liquid chromatography with fluorescence detection was used to determine the plasma levels of pyridoxal-5'-phosphate (PLP) and total homocysteine (tHcy). Area under the curve (AUC) for assessing the diagnostic accuracy of folate-related data through an FFQ was 0.74 (Pfasting plasma concentrations. Our data supported the validity of new FFQ to rank individuals by dietary intake status of folate and cobalamin.

  6. Hyperhomocysteinemia and neurologic disorders: a review.

    Science.gov (United States)

    Ansari, Ramin; Mahta, Ali; Mallack, Eric; Luo, Jin Jun

    2014-10-01

    Homocysteine (Hcy) is a sulfur-containing amino acid that is generated during methionine metabolism. It has a physiologic role in DNA metabolism via methylation, a process governed by the presentation of folate, and vitamins B6 and B12. Physiologic Hcy levels are determined primarily by dietary intake and vitamin status. Elevated plasma levels of Hcy (eHcy) can be caused by deficiency of either vitamin B12 or folate, or a combination thereof. Certain genetic factors also cause eHcy, such as C667T substitution of the gene encoding methylenetetrahydrofolate reductase. eHcy has been observed in several medical conditions, such as cardiovascular disorders, atherosclerosis, myocardial infarction, stroke, minimal cognitive impairment, dementia, Parkinson's disease, multiple sclerosis, epilepsy, and eclampsia. There is evidence from laboratory and clinical studies that Hcy, and especially eHcy, exerts direct toxic effects on both the vascular and nervous systems. This article provides a review of the current literature on the possible roles of eHcy relevant to various neurologic disorders.

  7. Hyperhomocysteinemia as a risk factor for ischemic heart disease

    International Nuclear Information System (INIS)

    Amir, M.; Dilawar, M.; Ijaz, A.; Sattar, A.; Dawood, M.M.; Anwar, M.

    2004-01-01

    Objective: To determine association of hyperhomocysteinemia with myocardial infarction and conventional risk factors for ischemic heart disease. Patients and Methods: A total of 100 hospitalized patients having myocardial infarction (MI) were randomly selected comprising 85 males and 15 females. The average age of the patients was 53 plus minus 4.5 years. A similar number of age and gender-matched healthy controls were also selected. The demographic details, history and clinical examination of both patients and controls were recorded and their blood was collected in fasting state for estimation of serum total cholesterol, plasma glucose and serum total homocysteine. Results: Serum total homocysteine level in controls was significantly lower (10.8 plus minus 4.1 micro mol/L) as compared to patients (18.0 plus minus 5.9 micro mol/L) (p < 0.0001). Smoking showed statistically significant association with hyperhomocysteinemic patients (p = 0.04). Conclusion: Ischemic heart disease was associated with moderate hyperhomocysteinemia in our patients and it was also associated with smoking. (author)

  8. [Factors associated with hyperhomocysteinemia in inflammatory bowel disease: prospective study in 81 patients].

    Science.gov (United States)

    Roblin, X; Germain, E; Phelip, J M; Ducros, V; Pofelski, J; Heluwaert, F; Oltean, P; Faucheron, J L; Bonaz, B

    2006-02-01

    A high prevalence (52%) of hyperhomocysteinemia is observed in Crohn disease (CD), however it is not well documented in ulcerative colitis (UC). Furthermore, in the different works studying hyperhomocysteinemia the associated factors are different. Prospective evaluation of hyperhomocysteinemia in inflammatory bowel disease (IBD) patients, of the risk factors and the determination of a potential risk of colorectal carcinoma in case of hyperhomocysteinemia. IBD patients followed in our department were prospectively recruited between November 2003-September 2004. To be included patients should have passed a coloscopy in the two years. Patients with kidney failure or drugs supposed, to interfere with homocystéine metabolism (folates, vitamin B12, methotrexate) were excluded from the study. The following parameters were analysed: age, sex, clinical activity indexes (CDAI for Crohn disease and CAI for ulcerative colitis), length-extent and type of the disease (CD or UC), smoking, plasma homocystein concentration, folates and vitamin B12. Eighty-one patients (60 CD, 21 UC, mean age 43.8 +/- 17.3) were included, 30 had an active disease at inclusion and 16 were smokers. The prevalence of high homocystein concentration was 55.6%. In univariate analysis a low rate of folates was the only risk factor for a high homocystein concentration (74 vs. 52.8%; P = 0.018). Smoking was almost an associated factor. In multivariate analysis, a low rate of folate was the only risk factor of hyperhomocysteinemia, OR = 3.59 [1.27-10.17]. Five endoscopic lesions considered as precancerous were described; these patients had all a hyperhomocysteinemia. The prevalence of hyperhomocysteinemia is high in UC and in CD. A low folate rate is the only risk factor observed in our study. There is a possible link between colorectal cancer and hyperhomocysteinemia. A high Plasma homocystein concentration must be search in inflammatory bowel disease patients and a substitutive treatment of folates and

  9. Successful intrauterine treatment of a patient with cobalamin C defect

    Directory of Open Access Journals (Sweden)

    Friedrich K. Trefz

    2016-03-01

    Full Text Available Cobalamin C (cblC defect is an inherited autosomal recessive disorder that affects cobalamin metabolism. Patients are treated with hydroxycobalamin to ameliorate the clinical features of early-onset disease and prevent clinical symptoms in late-onset disease. Here we describe a patient in whom prenatal maternal treatment with 30 mg/week hydroxycobalamin and 5 mg/day folic acid from week 15 of pregnancy prevented disease manifestation in a girl who is now 11 years old with normal IQ and only mild ophthalmic findings. The affected older sister received postnatal treatment only and is severely intellectually disabled with severe ophthalmic symptoms. This case highlights the potential of early, high-dose intrauterine treatment in a fetus affected by the cblC defect.

  10. Clinical characteristics of hemolytic uremic syndrome secondary to cobalamin C disorder in Chinese children.

    Science.gov (United States)

    Li, Qi-Liang; Song, Wen-Qi; Peng, Xiao-Xia; Liu, Xiao-Rong; He, Le-Jian; Fu, Li-Bing

    2015-08-01

    The present study was undertaken to investigate the clinical characteristics of hemolytic uremic syndrome (HUS) secondary to cobalamin C disorder (cbl-C disorder). We reviewed retrospectively the medical records of 3 children with HUS secondary to cbl-C disorder who had been treated between April 1, 2009 and October 31, 2013. The 3 patients with HUS secondary to cbl-C disorder presented with progressive hemolytic anemia, acute renal failure, thrombocytopenia, poor feeding, and failure to thrive. Two of the 3 patients once had high blood pressure. The mutations of c.609G>A (p.W203X), c.217C>T (p.R73X) and c.365A>T (p.H122L) in the methylmalonic aciduria (cobalamin deficiency) cbl-C type, with homocystinuria gene were detected in the 3 patients. In these patients the levels of lactate dehydrogenase and homocysteine in serum were elevated and the level of methylmalonic acid (MMA) in urine was also elevated. After treatment with hydroxocobalamin, 2 patients were discharged with no obvious abnormal growth and neurological development and 1 patient died of multiple organ failure. The results of this study demonstrated that cbl-C disorder should be investigated in any child presenting with HUS. The high concentrations of homocysteine and MMA could be used for timely recognization of the disease. Once the high levels of plasma homocystein and/or plasma or urine MMA are detected, the treatment with parenteral hydroxocobalamin should be prescribed immediately. The early diagnosis and treatment would contribute to the good prognosis of the disease.

  11. Evaluation of psychoacoustic tests and P300 event-related potentials in elderly patients with hyperhomocysteinemia.

    Science.gov (United States)

    Díaz-Leines, Sergio; Peñaloza-López, Yolanda R; Serrano-Miranda, Tirzo A; Flores-Ávalos, Blanca; Vidal-Ixta, Martha T; Jiménez-Herrera, Blanca

    2013-01-01

    Hyperhomocysteinemia as a risk factor for hearing impairment, neuronal damage and cognitive impairment in elderly patients is controversial and is limited by the small number of studies. The aim of this work was determine if elderly patients detected with hyperhomocysteinemia have an increased risk of developing abnormalities in the central auditory processes as compared with a group of patients with appropriate homocysteine levels, and to define the behaviour of psychoacoustic tests and long latency potentials (P300) in these patients. This was a cross-sectional, comparative and analytical study. We formed a group of patients with hyperhomocysteinemia and a control group with normal levels of homocysteine. All patients underwent audiometry, tympanometry and a selection of psychoacoustic tests (dichotic digits, low-pass filtered words, speech in noise and masking level difference), auditory evoked brainstem potentials and P300. Patients with hyperhomocysteinemia had higher values in the test of masking level difference than did the control group (P=.049) and more protracted latency in P300 (P=.000). Hyperhomocysteinemia is a factor that alters the central auditory functions. Alterations in psychoacoustic tests and disturbances in electrophysiological tests suggest that the central portion of the auditory pathway is affected in patients with hyperhomocysteinemia. Copyright © 2012 Elsevier España, S.L. All rights reserved.

  12. Characterization and immunohistochemical localization of rat salivary cobalamin-binding protein and comparison with human salivary haptocorrin

    DEFF Research Database (Denmark)

    Nexø, Ebba; Poulsen, Steen Seier

    1985-01-01

    Rat saliva contains a cobalamin-binding protein that binds cobalamin as well as cobinamide. The protein binds cobalamin with an affinity constant of 8 X 10(10) l X mol-1, and it binds cobalamin over a more narrow pH range (pH 7.5-10) than does human haptocorrin. It has a Stokes radius of 2.45 nm...

  13. Insights into the reactivation of cobalamin-dependent methionine synthase

    Energy Technology Data Exchange (ETDEWEB)

    Koutmos, Markos; Datta, Supratim; Pattridge, Katherine A.; Smith, Janet L.; Matthews, Rowena G.; (Michigan)

    2009-12-10

    Cobalamin-dependent methionine synthase (MetH) is a modular protein that catalyzes the transfer of a methyl group from methyltetrahydrofolate to homocysteine to produce methionine and tetrahydrofolate. The cobalamin cofactor, which serves as both acceptor and donor of the methyl group, is oxidized once every {approx}2,000 catalytic cycles and must be reactivated by the uptake of an electron from reduced flavodoxin and a methyl group from S-adenosyl-L-methionine (AdoMet). Previous structures of a C-terminal fragment of MetH (MetH{sup CT}) revealed a reactivation conformation that juxtaposes the cobalamin- and AdoMet-binding domains. Here we describe 2 structures of a disulfide stabilized MetH{sup CT} ({sub s-s}MetH{sup CT}) that offer further insight into the reactivation of MetH. The structure of {sub s-s}MetH{sup CT} with cob(II)alamin and S-adenosyl-L-homocysteine represents the enzyme in the reactivation step preceding electron transfer from flavodoxin. The structure supports earlier suggestions that the enzyme acts to lower the reduction potential of the Co(II)/Co(I) couple by elongating the bond between the cobalt and its upper axial water ligand, effectively making the cobalt 4-coordinate, and illuminates the role of Tyr-1139 in the stabilization of this 4-coordinate state. The structure of {sub s-s}MetH{sub CT} with aquocobalamin may represent a transient state at the end of reactivation as the newly remethylated 5-coordinate methylcobalamin returns to the 6-coordinate state, triggering the rearrangement to a catalytic conformation.

  14. Corrective effects of hepatotoxicity by hepatic Dyrk1a gene delivery in mice with intermediate hyperhomocysteinemia

    Directory of Open Access Journals (Sweden)

    Alizée Latour

    2015-03-01

    Full Text Available Hyperhomocysteinemia results from hepatic metabolism dysfunction and is characterized by a high plasma homocysteine level, which is also an independent risk factor for cardiovascular disease. Elevated levels of homocysteine in plasma lead to hepatic lesions and abnormal lipid metabolism. Therefore, lowering homocysteine levels might offer therapeutic benefits. Recently, we were able to lower plasma homocysteine levels in mice with moderate hyperhomocysteinemia using an adenoviral construct designed to restrict the expression of DYRK1A, a serine/threonine kinase involved in methionine metabolism (and therefore homocysteine production, to hepatocytes. Here, we aimed to extend our previous findings by analyzing the effect of hepatocyte-specific Dyrk1a gene transfer on intermediate hyperhomocysteinemia and its associated hepatic toxicity and liver dysfunction. Commensurate with decreased plasma homocysteine and alanine aminotransferase levels, targeted hepatic expression of DYRK1A in mice with intermediate hyperhomocysteinemia resulted in elevated plasma paraoxonase-1 and lecithin:cholesterol acyltransferase activities and apolipoprotein A–I levels. It also rescued hepatic apolipoprotein E, J, and D levels. Further, Akt/GSK3/cyclin D1 signaling pathways in the liver of treated mice were altered, which may help prevent homocysteine-induced cell cycle dysfunction. DYRK1A gene therapy could be useful in the treatment of hyperhomocysteinemia in populations, such as end-stage renal disease patients, who are unresponsive to B-complex vitamin therapy.

  15. Effect of gastric anacidity on the intestinal absorption of liver bound 57Co-labelled cobalamins

    International Nuclear Information System (INIS)

    Kittang, E.

    1987-01-01

    57 Co-labelled cyanocobalamin injected in rabbit was transformed within the liver to 57 Co-labelled desoxyadenosylcobalamin and methylcovalamin. The absorption of 57 Co-labelled liver bound cobalamins could be determined with acceptable accuracy by the double isotope fecal excretion method. Treatment with the H 2-receptor antagonist, ranitidine, did not result in decreased absorption of 57 Co-labelled liver bound cobalamins in healthy individuals. R-protein and the R-proteincobalamin complex were determined by the FPLC Mono S chromatography method with a high degree of correlation to the charcoal method in saliva, gastric and duodenal juice, and with a high degree of reproducibility. Omeprazole markedly inhibited the gastric acid and pepsin secretion, but did nor inhibit the IF secretion. Omeprazole treatment resulted in anacidity in 14 of 17 individuals, but did not reduce the absorption of liver bound 57 Co-labelled cobalamins. The intrinsic factor concentration in gastric aspirates measured during the study was unchanged during omeprazole treatment. The release of cobalamins from liver homogenate was markedly inhibited by neutralized gastric juice in vitro, probably due to decreased pepsin mediated proteolysis. In vivo the cobalamin release from liver homogenate was modestly inhibited in the stomach but was unaffected in jejunum during omeprazole treatment. The major part of 57 Co-labelled liver cobalamins bound to R-protein in acid and neutral gastric juice in vitro, and omeprazole induced anacidity, did not influence the cobalamin binding either in gastric or jejunal juice in vivo

  16. Hyperhomocysteinemia and mortality after coronary artery bypass grafting.

    Directory of Open Access Journals (Sweden)

    Domenico Girelli

    Full Text Available BACKGROUND: The independent prognostic impact, as well as the possible causal role, of hyperhomocysteinemia (HHcy in coronary artery disease (CAD is controversial. No previous study specifically has addressed the relationship between HHcy and mortality after coronary artery bypass grafting (CABG surgery. The aim of this study is to evaluate the prognostic impact of HHcy after CABG surgery. METHODOLOGY AND PRINCIPAL FINDINGS: We prospectively followed 350 patients who underwent elective CABG between May 1996 and May 1999. At baseline, fasting total homocysteine (tHcy levels were measured in all participants, and a post-methionine loading (PML test was performed in 77.7% of them (n = 272. After a median follow-up of 58 months, 33 patients (9.4% had died, 25 because of cardiovascular events. HHcy, defined by levels higher than the 90th percentile (25.2 micromol/L of the population's distribution, was significantly associated to total and cardiovascular mortality (P = 0.018 [log-rank test 5.57]; P = 0.002 [log-rank test 9.76], respectively. The PML test had no prognostic value. After multiple adjustment for other univariate predictors by Cox regression, including statin therapy (the most powerful predictor in uni-/multivariate analyses, high-sensitivity C Reactive Protein (hs-CRP levels, and all known major genetic (MTHFR 677C-->T polymorphism and non-genetic (B-group vitamin status and renal function tHcy determinants, HHcy remained an independent prognostic factor for mortality (HRs: 5.02, 95% CIs 1.88 to 13.42, P = 0.001. CONCLUSIONS: HHcy is an important prognostic marker after CABG, independent of modern drug therapy and biomarkers.

  17. Free and protein-bound cobalamin absorption in healthy middle-aged and older subjects.

    Science.gov (United States)

    van Asselt, D Z; van den Broek, W J; Lamers, C B; Corstens, F H; Hoefnagels, W H

    1996-08-01

    To study free- and protein-bound cobalamin absorption and the correlation with atrophic gastritis in healthy middle-aged and older subjects. A cross-sectional study. Fifty-two healthy subjects, aged 26 to 87 years, apparently free from conditions known to influence the cobalamin status. Middle-aged subjects were defined as those younger than 65 years of age (median age 57 years) and older subjects as those 65 years and older (median age 75 years). Protein-bound cobalamin absorption was assessed by 48-hour urinary excretion method following oral administration of scrambled egg yolk, labeled in vivo with 57 Co-cobalamin by injecting a hen with 57 Co-cyanocobalamin. The percentage of 57 Co-cobalamin bound to protein was 65%. Free cobalamin absorption was assessed by 48-hour urinary excretion method following oral administration of crystalline 57 Co-cyanocobalamin. Plasma cobalamin, folate and fasting plasma gastrin, and pepsinogen A and C concentrations were determined. The median urinary excretion of egg yolk 57 Co-cobalamin in middle-aged subjects was 12.3% (25th and 75th percentiles 10.5%-14.5%) compared with 11.7% (25th and 75th percentiles 9.8%-13.6%) in older subjects (P = .283). The median urinary excretion after administration of free 57 Co-cobalamin in middle-aged subjects was 25.7% (25th and 75th percentiles 20.6%-30.7%) compared with 27.9% (25th and 75th percentiles 21.4%-34.5%) in older subjects (P = .694). Neither egg yolk nor free 57 Co-cobalamin excretion correlated with age. A ratio of pepsinogen A to pepsinogen C less than 1.6, indicating atrophic gastritis, was found in 13 subjects. Within the atrophic gastritis group, 11 subjects had a pepsinogen A concentration greater than or equal to 17 micrograms/L, indicating mild to moderate atrophic gastritis, and two subjects had a pepsinogen A concentration less than 17 micrograms/L, indicating severe atrophic gastritis or gastric atrophy. All subjects had normal fasting plasma gastrin concentrations. Free

  18. Cobalamin status during normal pregnancy and postpartum: a longitudinal study comprising 406 danish women

    DEFF Research Database (Denmark)

    Milman, N; Byg, KE; Bergholt, T

    2006-01-01

    -) cobalamin, P-methylmalonic acid and P-homocysteine was measured at 18, 32 and 39 wk gestation and 8 wk postpartum during lactation. RESULTS: P-cobalamin showed a gradual, significant decline during pregnancy (P ... and 8 wk postpartum median values were 225, 172, 161 and 319 pmol/L, respectively. P-methylmalonic displayed a gradual, significant increase during pregnancy as well as postpartum (P homocysteine demonstrated...

  19. [Vitamin B12 deficiency: what's new?].

    Science.gov (United States)

    Braillard, O; Casini, A; Samii, K; Rufenacht, P; Junod, Perron N

    2012-09-26

    Vitamin B12 screening is only recommended among symptomatic patients or in those with risk factors. The main cause of vitamin B12 deficiency is the food cobalamin malabsorption syndrom. Holotranscobalamin is a more reliable marker than cyanocobalamin to confirm vitamin B12 deficiency, but it has not been validated yet in complex situations. An autoimmune gastritis must be excluded in the absence of risk factors but in the presence of a probable deficiency. Oral substitution treatment is effective but requires excellent therapeutic compliance and close follow-up to monitor the response to treatment. It has not yet been studied among patients suffering from severe symptoms, inflammatory bowel disease and ileal resection.

  20. Migraine with Ischemic Stroke in a Young Male with Hyperhomocysteinemia and Connective Tissue Dysplasia

    Directory of Open Access Journals (Sweden)

    S.K. Yevtushenko

    2014-08-01

    Full Text Available Case report of migraine with ischemic stroke on the background of hyperhomocysteinemia in a young male with connective tissue dysplasia is given in the article. The clinical picture, results of magnetic resonance imaging, tomography, genetic and somatic examination are described.

  1. CBS mutations and MTFHR SNPs causative of hyperhomocysteinemia in Pakistani children.

    Science.gov (United States)

    Ibrahim, Shahnaz; Maqbool, Saadia; Azam, Maleeha; Iqbal, Mohammad Perwaiz; Qamar, Raheel

    2018-03-29

    Three index patients with hyperhomocysteinemia and ocular anomalies were screened for cystathionine beta synthase (CBS) and methylenetetrahydrofolate reductase (MTHFR) polymorphisms. Genotyping of hyperhomocysteinemia associated MTHFR polymorphisms C677T (rs1801133) and A1298C (rs1801131) was done by PCR-restriction fragment length polymorphism. Sanger sequencing was performed for CBS exonic sequences along with consensus splice sites. In the case of MTHFR polymorphisms, all the patients were heterozygous CT for the single nucleotide polymorphism (SNP) C677T and were therefore carriers of the risk allele (T), while the patients were homozygous CC for the risk genotype of the SNP A1298C. CBS sequencing resulted in the identification of two novel mutations, a missense change (c.467T>C; p.Leu156Pro) in exon 7 and an in-frame deletion (c.808_810del; p.Glu270del) in exon 10. In addition, a recurrent missense mutation (c.770C>T; p.Thr257Met) in exon 10 of the gene was also identified. The mutations were present homozygously in the patients and were inherited from the carrier parents. This is the first report from Pakistan where novel as well as recurrent CBS mutations causing hyperhomocysteinemia and lens dislocation in three patients from different families are being reported with the predicted effect of the risk allele of the MTHFR SNP in causing hyperhomocysteinemia.

  2. Brief Report: Childhood Disintegrative Disorder as a Likely Manifestation of Vitamin B12 Deficiency

    Science.gov (United States)

    Malhotra, Savita; Subodh, B. N.; Parakh, Preeti; Lahariya, Sanjay

    2013-01-01

    Childhood disintegrative disorder is a rare disorder, characterized by regression of acquired skills after a period of normal development. The case of childhood disintegrative disorder presented here was found to have vitamin B12 deficiency and hyperhomocysteinemia on extensive evaluation to find a probable cause for regression. This case…

  3. A Prospective, Placebo-Controlled Pilot Evaluation of the Effect of Omeprazole on Serum Calcium, Magnesium, Cobalamin, Gastrin Concentrations, and Bone in Cats.

    Science.gov (United States)

    Gould, E; Clements, C; Reed, A; Giori, L; Steiner, J M; Lidbury, J A; Suchodolski, J S; Brand, M; Moyers, T; Emery, L; Tolbert, M K

    2016-05-01

    Chronic proton pump inhibitor administration has been associated with electrolyte and cobalamin deficiency, disrupted bone homeostasis, hypergastrinemia, and rebound acid hypersecretion in humans. It is unknown if this occurs in cats. Prolonged oral omeprazole results in altered bone mineral density or content, serum calcium, magnesium, cobalamin, and gastrin concentrations in healthy cats. Six healthy adult DSH cats. In a within subjects, before and after design, cats received placebo followed by omeprazole (0.83-1.6 mg/kg PO q12h) for 60 days each. Analysis of serum calcium, magnesium, cobalamin, and gastrin concentrations was performed on days 0, 30, and 60. Bone density and content were evaluated on days 0 and 60 of each intervention. Continuous data were analyzed using a two-way ANOVA (α = 0.006). On day 60 of omeprazole administration, continuous intragastric pH monitoring was performed in 2 cats to evaluate the effects of abrupt withdrawal of omeprazole. No significant changes were detected between treatments for any variables, except serum gastrin, which was significantly higher during omeprazole treatment in comparison to placebo (P = 0.002). Evidence of gastric hyperacidity was seen in both cats in which intragastric pH monitoring was performed following cessation of omeprazole. Although further studies with larger populations of cats will be needed to draw any definitive conclusions, these preliminary results suggest that prolonged PPI treatment results in hypergastrinemia and abrupt PPI withdrawal might result in RAH in cats. Copyright © 2016 The Authors. Journal of Veterinary Internal Medicine published by Wiley Periodicals, Inc. on behalf of the American College of Veterinary Internal Medicine.

  4. Effects of maternal hyperhomocysteinemia induced by high methionine diet on the learning and memory performance in offspring.

    Science.gov (United States)

    Baydas, Giyasettin; Koz, Sema T; Tuzcu, Mehmet; Nedzvetsky, Victor S; Etem, Ebru

    2007-05-01

    In this study, we suggest that chronic maternal hyperhomocysteinemia results in learning deficits in the offspring due to delayed brain maturation and altered expression pattern of neural cell adhesion molecule. Although the deleterious effects of hyperhomocysteinemia were extensively investigated in the adults, there is no clear evidence suggesting its action on the developing fetal rat brain and cognitive functions of the offspring. Therefore, in the present work we aimed to investigate effects of maternal hyperhomocysteinemia on the fetal brain development and on the behavior of the offspring. A group of pregnant rats received daily methionine (1 g/kg body weight) dissolved in drinking water to induce maternal hyperhomocysteinemia, starting in the beginning of gestational day 0. The levels of glial fibrillary acidic protein, S100B protein, and neural cell adhesion molecule were determined in the tissue samples from the pups. Learning and memory performances of the young-adult offsprings were tested using Morris water maze test. There were significant reductions in the expressions of glial fibrillary acidic protein and S100B protein in the brains of maternally hyperhomocysteinemic pups on postnatal day 1, suggesting that hyperhomocysteinemia delays brain maturation. In conclusion, maternal hyperhomocysteinemia changes the expression pattern of neural cell adhesion molecule and therefore leads to an impairment in the learning performance of the offspring.

  5. Determination of vitamin B12 (cobalamine) absorption by means of a simple double-isotope technique

    International Nuclear Information System (INIS)

    Hippe, E.; Brynskov, J.; Gimsing, P.; Hjelt, K.

    1986-01-01

    The background, practical instruction and clinical results of a simplified method of determining the absorption of cobalamine (vitamin B 12 ) are presented. The simultaneous administration of 57 CO-CN-cobalamine, a non-absorbable marker ( 51 CrCl 3 ), and red carmine tablets enable quantitative assessments of the cobalamine absorption by collection of a small red feaces sample. In contrast to the classical Schilling-test, this vitamin B 12 absorption test (B 12 -ABS-test) or faeces-spot-test is, independent of fasting, flushing dose, renal function and diurnal urinary collection. This is documented in a series of clinical studies. The B 12 -ABS-test provides accurate and precise results compared to the reference method (whole-body-counting). The Schilling test, on the contrary, gives approximately 50% false low values in a reference group of elderly hospitalized patients. A modification of the B 12 -ABS-test, has been used to determine the cobalamine absorption in children, and a set of age-related reference intervals have been established, together with quantitative measurements of the cobalamine absorption in children with small bowel diseases. Based on several years of practical experience, we recommend replacement of the Schilling test by this simple double-isotope technique. (author)

  6. Synthesis and characterization of nido-carborane-cobalamin conjugates

    International Nuclear Information System (INIS)

    Hogenkamp, Harry P.C.; Collins, Douglas A.; Live, David; Benson, Linda M.; Naylor, Stephen

    2000-01-01

    Three vitamin B 12 (cyanocobalamin) conjugates bearing one nido-carborane molecule or two nido-carborane molecules linked to the propionamide side chains via a four carbon linker have been synthesized. Reaction of o-carboranoylchloride with 1,4-diaminobutane in pyridine produced nido-carboranoyl(4-amidobutyl)amine, which was linked to the b- and d-monocarboxylic acids and the b,d-dicarboxylic acid of cyanocobalamin. Mass spectrometry analysis as well as 11 B nuclear magnetic resonance demonstrated that during the reaction of o-carboranonylchloride with diaminobutane one of the boron atoms was eliminated. In vitro biological activity of the cyanocobalamin-nido-carborane conjugates was assessed by the unsaturated vitamin B 12 binding capacity assay. When compared with 57 Co cyanocobalamin, the biological activity of cyanocobalamin-b-nido-carborane, cyanocobalamin-d-nido-carborane, and cyanocobalamin-b-d-bis-nido-carborane conjugates were 92.93%, 35.75%, and 37.02%, respectively. These findings suggest that the 10 B cobalamin conjugates might be useful agents in treating malignant tumors via neutron capture therapy

  7. Increase in circulating holotranscobalamin after oral administration of cyanocobalamin or hydroxocobalamin in healthy adults with low and normal cobalamin status

    DEFF Research Database (Denmark)

    Greibe, Eva; Mahalle, Namita; Bhide, Vijayshri

    2017-01-01

    PURPOSE: To investigate the absorption of synthetic cyanocobalamin and natural occurring hydroxocobalamin in populations with low and normal cobalamin (vitamin B12) status. METHODS: We included adults with low (n = 59) and normal (n = 42) cobalamin status and measured the change in serum holotran...

  8. Hyperhomocyst(einemia in chronic stable renal transplant patients

    Directory of Open Access Journals (Sweden)

    David José de Barros Machado

    2000-10-01

    Full Text Available PURPOSE: Hyperhomocyst(einaemia is an important risk factor for atherosclerosis, which is currently a major cause of death in renal transplant patients. The aim of this study was to assess the influence of immunosuppressive therapy on homocyst(einemia in renal transplant recipients. METHODS: Total serum homocysteine (by high performance liquid chromatography, creatinine, lipid profile, folic acid (by radioimmunoassay-RIA and vitamin B12 (by RIA concentrations were measured in 3 groups. Group I patients (n=20 were under treatment with cyclosporine, azathioprine, and prednisone; group II (n=9 were under treatment with azathioprine and prednisone; and group III (n=7 were composed of renal graft donors for groups I and II. Creatinine, estimated creatinine clearance, cyclosporine trough level, lipid profile, folic acid, and vitamin B12 concentrations and clinical characteristics of patients were assessed with the aim of ascertaining determinants of hyperhomocyst(einemia. RESULTS: Patient ages were 48.8 ± 15.1 yr (group I, 43.3 ± 11.3 yr (group II; and 46.5 ± 14.8 yr (group III. Mean serum homocyst(eine (tHcy concentrations were 18.07 ± 8.29 mmol/l in renal transplant recipients; 16.55 ± 5.6 mmol/l and 21.44 ± 12.1 mmol/l respectively for group I (with cyclosporine and group II (without cyclosporine (NS. In renal donors, tHcy was significantly lower (9.07 ± 3.06 mmol/l; group I + group II vs. group III, pOBJETIVOS: A hiper-homocisteinemia é um fator de risco importante para aterosclerose e, esta é uma das principais causas de óbito em transplantados renais. O objetivo deste estudo é avaliar a influência da terapêutica imunossupressora na homocisteinemia de receptores de transplante renal. CASUÍSTICA E MÉTODO: Vinte e nove pacientes foram divididos em dois grupos: grupo I (n=20 - pacientes transplantados renais em uso de ciclosporina, azatioprina e prednisona; grupo II (n=9 - pacientes transplantados renais em uso de azatioprina e

  9. Combined Effect of Hyperhomocysteinemia and Hypertension on the Presence of Early Carotid Artery Atherosclerosis.

    Science.gov (United States)

    Zhang, Zhongying; Fang, Xianghua; Hua, Yang; Liu, Beibei; Ji, Xunming; Tang, Zhe; Wang, Chunxiu; Guan, Shaochen; Wu, Xiaoguang; Liu, Hongjun; Gu, Xiang

    2016-05-01

    To examine the individual effect of elevated homocysteine and its combined effect with hypertension on early carotid artery atherosclerosis (ECAS). We recruited 1257 subjects from a community-based population in Beijing, China, aged 55 years and older. The definition of hyperhomocysteinemia was referred to as the presence of homocysteine concentrations greater than 15 µmol/L. Carotid intima-media thickness (CIMT), plaque, the sum of plaque thickness (plaque score, PS), and plaque location in common carotid artery were established by ultrasonography. The presence of increased CIMT (≥1.0 mm) and plaque was defined as ECAS. Age, sex, smoking, alcohol drinking, physical activity, total cholesterol, glucose, estimated glomerular filtration rate, hypoglycemic therapy, and lipid-lowering therapy were adjusted by logistic regression analysis. After adjustments for all potential confounders, the risks of presence of plaque, bilateral plaque, and high PS were significantly higher in the group with hyperhomocysteinemia as compared with reference group (the normal homocysteine and normotensive). The odds ratios (ORs) were 1.56 for presence of plaque (95% CI 1.05-2.33), 1.80 for bilateral plaque (95% CI 1.08-2.99), and 1.90 for high PS (95% CI 1.09-3.30), respectively. The group with both hyperhomocysteinemia and hypertension manifested the highest ORs of ECAS. The fully adjusted ORs were 1.67 for increased CIMT (95% CI 1.15-2.42), 2.48 for bilateral plaques (95% CI 1.54-3.99), and 2.69 for high PS (95% CI 1.61-4.47), correspondingly. Elevated homocysteine had a mild-to-moderate independent effect on ECAS. Combined with hypertension, hyperhomocysteinemia might increase the strength of the above-mentioned effects. Copyright © 2016 National Stroke Association. Published by Elsevier Inc. All rights reserved.

  10. [Metabolic status and bone mineral density in patients with pseudarthrosis of long bones in hyperhomocysteinemia].

    Science.gov (United States)

    Bezsmertnyĭ, Iu O

    2013-06-01

    In article described research of the metabolic status and bone mineral density in 153 patients with with pseudarthrosis of long bones, in individuals with consolidated fractures and healthy people. The violations of reparative osteogenesis at hyperhomocysteinemia are accompanied by disturbances of the functional state of bone tissue, inhibition of biosynthetic and increased destruction processes, reduced bone mineral density in the formation of osteopenia and osteoporosis. The degree and direction of change of bone depends on the type of violation of reparative osteogenesis.

  11. Impact of Gene rs7422339 Polymorphism in Argentine Patients With Hyperhomocysteinemia

    Directory of Open Access Journals (Sweden)

    Silene M. Silvera-Ruiz BSc

    2015-05-01

    Full Text Available Carbamoyl phosphate synthetase 1 ( CPS1 is a key gene in the first step of urea cycle and has been correlated with nitric oxide level and vascular smooth muscle activity. A functional single-nucleotide polymorphism C/A at position 4217 in CPS1 (National Center for Biotechnology Information SNP database no. rs7422339, T1405N was reported to be associated with high homocysteine (Hcy plasma values. Although genetic variants of methylenetetrahydrofolate reductase ( MTHFR gene are known to influence Hcy concentration, other genetic determinants of Hcy remain largely unknown. The association between the CPS1 rs7422339 and the risk of hyperhomocysteinemia in Latin American populations is unknown. Here, we study this association in 100 patients having hyperhomocysteinemia without MTHFR c.677C>T polymorphism and 100 controls. CPS1 rs7422339 was studied using polymerase chain reaction and enzymatic restriction. Comparisons of the CPS1 rs7422339 genotype distributions revealed a significant difference between groups ( P = 2.3 × 10 −3 . Patients carrying polymorphic allele showed almost 3 times higher risk (odds ratio [OR] = 2.47 of hyperhomocysteinemia than wild-type allele, suggesting that rs7422339 SNP is associated with high Hcy levels in the Argentine population.

  12. Hyperhomocysteinemia in bilateral anterior ischemic optic neuropathy after conventional coronary artery bypass graft: a case report.

    Science.gov (United States)

    Niro, A; Sborgia, G; Sborgia, A; Alessio, G

    2018-01-17

    The incidence of anterior ischemic optic neuropathy after coronary artery bypass graft procedures ranges from 1.3 to 0.25%. The mechanisms of anterior ischemic optic neuropathy after cardiovascular procedures remain undefined but many systemic and related-to-surgery risk factors could underlie anterior ischemic optic neuropathy. In this case, we report a rare presentation of a bilateral anterior ischemic optic neuropathy after coronary artery bypass graft and speculate on the preoperative hyperhomocysteinemia as an independent risk factor for anterior ischemic optic neuropathy. A 56-year-old white man, a tobacco smoker with type 2 diabetes and coronary artery disease, underwent a conventional coronary artery bypass graft with extracorporeal circulation. In spite of ongoing anti-aggregation, antithrombotic, and vasodilator therapy, 10 days after the surgery he complained of severe bilateral visual loss. Funduscopy and fluorescein angiography revealed a bilateral anterior ischemic optic neuropathy. Analysis of preoperative laboratory tests revealed hyperhomocysteinemia. Hyperhomocysteinemia could increase the risk of ocular vascular damage and bilateral ocular involvement in patients who have undergone conventional coronary artery bypass graft.

  13. EFSA NDA Panel (EFSA Panel on Dietetic Products, Nutrition and Allergies), 2015. Scientific Opinion on Dietary Reference Values for cobalamin (vitamin B12)

    DEFF Research Database (Denmark)

    Tetens, Inge

    2015-01-01

    Following a request from the European Commission, the EFSA Panel on Dietetic Products, Nutrition and Allergies (NDA) derived Dietary Reference Values (DRVs) for cobalamin (vitamin B12). The Panel considers that the approach based on a combination of biomarkers of cobalamin status, i.e. serum....... For pregnancy and lactation, additional cobalamin intakes related to the accumulation of cobalamin in fetal tissues and transfer of cobalamin into breast milk are considered and AIs of 4.5 and 5 μg/day, respectively, are proposed....

  14. Functional Genomics and Phylogenetic Evidence Suggest Genus-Wide Cobalamin Production by the Globally Distributed Marine Nitrogen Fixer Trichodesmium.

    Science.gov (United States)

    Walworth, Nathan G; Lee, Michael D; Suffridge, Christopher; Qu, Pingping; Fu, Fei-Xue; Saito, Mak A; Webb, Eric A; Sañudo-Wilhelmy, Sergio A; Hutchins, David A

    2018-01-01

    Only select prokaryotes can biosynthesize vitamin B 12 (i.e., cobalamins), but these organic co-enzymes are required by all microbial life and can be vanishingly scarce across extensive ocean biomes. Although global ocean genome data suggest cyanobacteria to be a major euphotic source of cobalamins, recent studies have highlighted that >95% of cyanobacteria can only produce a cobalamin analog, pseudo-B 12 , due to the absence of the BluB protein that synthesizes the α ligand 5,6-dimethylbenzimidizole (DMB) required to biosynthesize cobalamins. Pseudo-B 12 is substantially less bioavailable to eukaryotic algae, as only certain taxa can intracellularly remodel it to one of the cobalamins. Here we present phylogenetic, metagenomic, transcriptomic, proteomic, and chemical analyses providing multiple lines of evidence that the nitrogen-fixing cyanobacterium Trichodesmium transcribes and translates the biosynthetic, cobalamin-requiring BluB enzyme. Phylogenetic evidence suggests that the Trichodesmium DMB biosynthesis gene, bluB , is of ancient origin, which could have aided in its ecological differentiation from other nitrogen-fixing cyanobacteria. Additionally, orthologue analyses reveal two genes encoding iron-dependent B 12 biosynthetic enzymes (cbiX and isiB), suggesting that iron availability may be linked not only to new nitrogen supplies from nitrogen fixation, but also to B 12 inputs by Trichodesmium . These analyses suggest that Trichodesmium contains the genus-wide genomic potential for a previously unrecognized role as a source of cobalamins, which may prove to considerably impact marine biogeochemical cycles.

  15. PKM2-dependent metabolic reprogramming in CD4+ T cells is crucial for hyperhomocysteinemia-accelerated atherosclerosis.

    Science.gov (United States)

    Lü, Silin; Deng, Jiacheng; Liu, Huiying; Liu, Bo; Yang, Juan; Miao, Yutong; Li, Jing; Wang, Nan; Jiang, Changtao; Xu, Qingbo; Wang, Xian; Feng, Juan

    2018-06-01

    Inflammation mediated by activated T cells plays an important role in the initiation and progression of hyperhomocysteinemia (HHcy)-accelerated atherosclerosis in ApoE -/- mice. Homocysteine (Hcy) activates T cells to secrete proinflammatory cytokines, especially interferon (IFN)-γ; however, the precise mechanisms remain unclear. Metabolic reprogramming is critical for T cell inflammatory activation and effector functions. Our previous study demonstrated that Hcy regulates T cell mitochondrial reprogramming by enhancing endoplasmic reticulum (ER)-mitochondria coupling. In this study, we further explored the important role of glycolysis-mediated metabolic reprogramming in Hcy-activated CD4 + T cells. Mechanistically, Hcy-activated CD4 + T cell increased the protein expression and activity of pyruvate kinase muscle isozyme 2 (PKM2), the final rate-limiting enzyme in glycolysis, via the phosphatidylinositol 3-kinase/AKT/mechanistic target of rapamycin signaling pathway. Knockdown of PKM2 by small interfering RNA reduced Hcy-induced CD4 + T cell IFN-γ secretion. Furthermore, we generated T cell-specific PKM2 knockout mice by crossing LckCre transgenic mice with PKM2 fl/fl mice and observed that Hcy-induced glycolysis and oxidative phosphorylation were both diminished in PKM2-deficient CD4 + T cells with reduced glucose and lipid metabolites, and subsequently reduced IFN-γ secretion. T cell-depleted apolipoprotein E-deficient (ApoE -/- ) mice adoptively transferred with PKM2-deficient CD4 + T cells, compared to mice transferred with control cells, showed significantly decreased HHcy-accelerated early atherosclerotic lesion formation. In conclusion, this work indicates that the PKM2-dependent glycolytic-lipogenic axis, a novel mechanism of metabolic regulation, is crucial for HHcy-induced CD4 + T cell activation to accelerate early atherosclerosis in ApoE -/- mice. Metabolic reprogramming is crucial for Hcy-induced CD4 + T cell inflammatory activation. Hcy activates

  16. Composite organization of the cobalamin binding and cubilin recognition sites of intrinsic factor

    DEFF Research Database (Denmark)

    Fedosov, Sergey N; Fedosova, Natalya U; Berglund, Lars

    2005-01-01

    Intrinsic factor (IF(50)) is a cobalamin (Cbl)-transporting protein of 50 kDa, which can be cleaved into two fragments: the 30 kDa N-terminal peptide IF(30) and the 20 kDa C-terminal glycopeptide IF(20). Experiments on binding of Cbl to IF(30), IF(20), and IF(50) revealed comparable association r...

  17. Transient plasma cobalamin elevation in patients with pneumonia - two case reports

    DEFF Research Database (Denmark)

    Rahbek, Martin Torp; Scheller, Rudolf; Nybo, Mads

    2018-01-01

    We report two cases of transient significantly elevated plasma cobalamin (B12) in geriatric patients acutely admitted with fever, increased C-reactive protein and X-ray verified pneumonia. Extensive diagnostic workup did not reveal kidney or liver disease, neither any signs of cancer. Furthermore...

  18. Some clinical and laboratory parameters of hemorrhagic fever with renal failure syndrome against the background correction of hyperhomocysteinemia

    Directory of Open Access Journals (Sweden)

    G. R. Syrtlanova

    2013-01-01

    Full Text Available The aim of the research was to curry out correction of hyperhomocysteinemia in patients with hemorrhagic fever with renal failure syndrome (HFRS and evaluate some clinical and laboratory parameters. The results of examining 91 men patients with HFRS at the age of 18 till 50 years old are presented. The vitamin complex «Angiovit» was used for hyperhomocysteinemia correction. The correction of hyperhomocysteinemia using the vitamin complex in all the three considered forms (mid, severs, complicated there are statistically significant decreases of homocysteine, the duration of oliguric stage and the concentration of creatinine in oliguric and diuretic stages in patients with HFRS compared with the group of patients having the generally basically therapy.

  19. Role of Hyperhomocysteinemia and Methylene Tetrahydrofolate Reductase C677T Polymorphism in Idiopathic Portal Vein Thrombosis.

    Science.gov (United States)

    Ghaznavi, Habib; Soheili, Zahra; Samiei, Shahram; Soltanpour, Mohammad Soleiman

    2016-03-01

    Portal vein thrombosis (PVT) is a rare and life-threatening vascular disorder characterized by obstruction or narrowing of the portal vein. Hyperhomocysteinemia and methylenetetrahydrofolate reductase (MTHFR) C677T polymorphism has been studied in PVT patients with conflicting results. In the present study the association of hyperhomocysteinemia and MTHFR C677T polymorphism with PVT risk was investigated in Iranians. Our study population consisted of 10 idiopathic PVT patients and 80 healthy control subjects matched for age and sex. MTHFR C677T polymorphism was genotyped by the polymerase chain reaction technique combined with restriction enzyme fragment length polymorphism (PCR-RFLP) technique and plasma total homocysteine (tHcy) levels were determined by enzyme immunoassay method. Mean plasma tHcy levels were significantly higher in PVT patients (20.2±6.8) than control subjects (10.9±4.7) (P=0.001). Moreover, plasma tHcy levels were significantly higher in 677T allele carriers relative to 677C allele carriers in both PVT patients (P=0.01) and control subjects (P=0.03). Neither homozygote nor heterozygote genotypes of MTHFR C677T polymorphism correlated significantly with PVT risk (P>0.05). Moreover, MTHFR C677T polymorphism didn't increase the risk of PVT under dominant (CT+TT vs. CC) or recessive (TT vs. CC+CT) genetic models analyzed (P>0.05). The difference in frequency of minor 677T allele between PVT patients and control subjects was not statistically significant (P>0.05). Based on the current study, we suggest that hyperhomocysteinemia constitutes a significant and common risk factor for PVT. Also, MTHFR C677T polymorphism is not a risk factor for PVT but is a contributing factor for elevated plasma tHcy levels.

  20. Diabetes Accelerates Retinal neuronal cell Death in A Mouse Model of endogenous Hyperhomocysteinemia

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    Preethi S. Ganapathy

    2009-01-01

    Full Text Available Hyperhomocysteinemia has been implicated in visual dysfunction. We reported recently that mice with endogenous hyperhomocysteinemia, due to mutation of the cystathionine-β-synthase ( cbs gene, demonstrate loss of neurons in the retinal ganglion cell (RGC layer and other retinal layers as homocysteine levels increase. Some clinical studies implicate hyperhomocysteinemia in the pathogenesis of diabetic retinopathy, which is also characterized by RGC loss. The present study used cbs +/– mice to determine whether modest elevation of plasma homocysteine, in the presence of diabetes, accelerates neuronal cell loss. Diabetes (DB was induced in 3 wk old cbs +/– and wildtype mice using streptozotocin; four groups of mice were studied: DB cbs +/– non-DB cbs +/– DB cbs +/+ ; non-DB cbs +/+ . One group of diabetic cbs +/– mice was maintained on a high methionine diet (HMD, 0.5% methionine drinking water to increase plasma homocysteine slightly. Eyes were harvested at 5, 10 and 15 weeks post-onset of diabetes; retinal cryosections were examined by light microscopy and subjected to systematic morphometric analysis. Diabetic cbs +/– had significantly fewer RGCs at 5 weeks compared to age-matched, non-diabetic cbs +/– and wildtype controls (10.0 ± 0.5 versus 14.9 ± 0.5 and 15.8 ± 0.6 cells/100 μm retina length, respectively. Significant differences in retinas of DB/high homocysteine versus controls were obtained 15 wks post-onset of diabetes including fewer RGCS and decreased thickness of inner nuclear and plexiform layers. Moderate increases in plasma homocysteine coupled with diabetes cause a more dramatic alteration of retinal phenotype than elevated homocysteine or diabetes alone and suggest that diabetes accelerates the retinal neuronal death in hyperhomocysteinemic mice.

  1. Diabetes Accelerates Retinal Neuronal Cell Death In A Mouse Model of Endogenous Hyperhomocysteinemia

    Directory of Open Access Journals (Sweden)

    Preethi S. Ganapathy

    2009-07-01

    Full Text Available Hyperhomocysteinemia has been implicated in visual dysfunction. We reported recently that mice with endogenous hyperhomocysteinemia, due to mutation of the cystathionine-β-synthase (cbs gene, demonstrate loss of neurons in the retinal ganglion cell (RGC layer and other retinal layers as homocysteine levels increase. Some clinical studies implicate hyperhomocysteinemia in the pathogenesis of diabetic retinopathy, which is also characterized by RGC loss. The present study used cbs+/- mice to determine whether modest elevation of plasma homocysteine, in the presence of diabetes, accelerates neuronal cell loss. Diabetes (DB was induced in 3 wk old cbs+/- and wildtype mice using streptozotocin; four groups of mice were studied: DB cbs+/-; non-DB cbs+/-; DB cbs+/+; non-DB cbs+/+. One group of diabetic cbs+/- mice was maintained on a high methionine diet (HMD, 0.5% methionine drinking water to increase plasma homocysteine slightly. Eyes were harvested at 5, 10 and 15 weeks post-onset of diabetes; retinal cryosections were examined by light microscopy and subjected to systematic morphometric analysis. Diabetic cbs+/- had significantly fewer RGCs at 5 weeks compared to age-matched, non-diabetic cbs+/- and wildtype controls (10.0 ± 0.5 versus 14.9 ± 0.5 and 15.8 ± 0.6 cells/100 µm retina length, respectively. Significant differences in retinas of DB/high homocysteine versus controls were obtained 15 wks post-onset of diabetes including fewer RGCS and decreased thickness of inner nuclear and plexiform layers. Moderate increases in plasma homocysteine coupled with diabetes cause a more dramatic alteration of retinal phenotype than elevated homocysteine or diabetes alone and suggest that diabetes accelerates the retinal neuronal death in hyperhomocysteinemic mice.

  2. Transient increase in homocysteine but not hyperhomocysteinemia during acute exercise at different intensities in sedentary individuals.

    Directory of Open Access Journals (Sweden)

    Eduardo Iglesias-Gutiérrez

    Full Text Available Considering that hyperhomocysteinemia is an independent risk factor for cardiovascular disease, the purpose of this study was to determine the kinetics of serum homocysteine (tHcy and the vitamins involved in its metabolism (folates, B(12, and B(6 in response to acute exercise at different intensities. Eight sedentary males (18-27 yr took part in the study. Subjects were required to complete two isocaloric (400 kcal acute exercise trials on separate occasions at 40% (low intensity, LI and 80% VO(2peak (high intensity, HI. Blood samples were drawn at different points before (pre4 and pre0 h, during (exer10, exer20, exer30, exer45, and exer60 min, and after exercise (post0, post3, and post19 h. Dietary, genetic, and lifestyle factors were controlled. Maximum tHcy occurred during exercise, both at LI (8.6 (8.0-10.1 µmol/L, 9.3% increase from pre0 and HI (9.4 (8.2-10.6 µmol/L, 25.7% increase from pre0, coinciding with an accumulated energy expenditure independent of the exercise intensity. From this point onwards tHcy declined until the cessation of exercise and continued descending. At post19, tHcy was not different from pre-exercise values. No values of hyperhomocysteinemia were observed at any sampling point and intensity. In conclusion, acute exercise in sedentary individuals, even at HI, shows no negative effect on tHcy when at least 400 kcal are spent during exercise and the nutritional status for folate, B(12, and B(6 is adequate, since no hyperhomocysteinemia has been observed and basal concentrations were recovered in less than 24 h. This could be relevant for further informing healthy exercise recommendations.

  3. "THE RELATION OF HYPERHOMOCYSTEINEMIA TO COGNITIVE FUNCTION AND BRAIN ATROPHY IN PATIENTS WITH MULTIPLE SCLEROSIS "

    Directory of Open Access Journals (Sweden)

    M. Ghaffarpour

    2007-06-01

    Full Text Available Cognitive impairment may be a common even at the onset of multiple sclerosis (MS. In this case-control study, we tried to find out the probable relationship between homocysteine levels and cerebral atrophy or cognitive impairment in patients with multiple sclerosis. One hundred fifty six patients who had MS according to McDonald diagnostic criteria were included in this study. Patients’ age, gender, and educational level, MS duration and clinical type, disability, cognitive function state based on minimental state examination (MMSE, presence of hyperhomocysteinemia, and brain atrophy were evaluated. There was no statistically significant relationship between hyperhomocysteinemia and cognitive status. Total homocysteine levels had a significant correlation with MMSE score only in those patients with elementary level of education. Also total homocysteine levels and overall cerebral atrophy did not indicate significant relationship according to those independent variables mentioned above except in the patients with EDSS less than 6. When intercaudate ratio > 0.10 was applied as a criterion for cerebral atrophy, we found that hyperhomocysteinemia related significantly to intercaudate ratio > 0.10 in females, aged between 21 and 30 years, MS duration ≤ 5 years, primary progressive MS and relapsing-remitting MS clinical types, EDSS ≤ 3 and elementary level of education. We suggest applying MMSE only for the first step of cognitive function survey. In the next steps, much more exact test must be used (e.g. MSNQ. Also we can not suggest measuring plasma homocysteine level as criterion for monitoring the cognitive function in patients with MS.

  4. Percutaneous balloon angioplasty for the treatment of iliofemoral arterial stenosis resulting from hyperhomocysteinemia in a child

    Energy Technology Data Exchange (ETDEWEB)

    Maynar, Manuel; Lopez-Benitez, Ruben [Diagnostic and Therapeutic Endoluminal Unit, Hospiten Rambla, Tenerife (Spain); Kirsch, David S.; Qian, Zhong [Department of Radiology, Louisiana State University Health Science Center, 1542 Tulane Avenue, LA 70112-2822, New Orleans (United States); Gomez-Sirvent, Jorge [Department of Pediatrics, Hospiten Rambla, Tenerife (Spain); Zerolo-Saez, Ignacio [Department of Surgery, Hospiten Rambla, Tenerife (Spain)

    2003-08-01

    Angioplasty has long been used in the treatment of peripheral arterial occlusive disease with variable long-term results. In this case report, we present a patient with marfanoid features and acute ischemia of the lower extremity. Angioplasty provided us with the means of emergently relieving the acute symptoms. The patient was subsequently found on further work-up to have hyperhomocysteinemia (HC) and appropriate medical therapy was initiated. We conclude that angioplasty should be considered in pediatric patients with acute occlusive limb ischemia, providing excellent immediate results to preserve the limb as well as the time to investigate the underlying causes. (orig.)

  5. Percutaneous balloon angioplasty for the treatment of iliofemoral arterial stenosis resulting from hyperhomocysteinemia in a child

    International Nuclear Information System (INIS)

    Maynar, Manuel; Lopez-Benitez, Ruben; Kirsch, David S.; Qian, Zhong; Gomez-Sirvent, Jorge; Zerolo-Saez, Ignacio

    2003-01-01

    Angioplasty has long been used in the treatment of peripheral arterial occlusive disease with variable long-term results. In this case report, we present a patient with marfanoid features and acute ischemia of the lower extremity. Angioplasty provided us with the means of emergently relieving the acute symptoms. The patient was subsequently found on further work-up to have hyperhomocysteinemia (HC) and appropriate medical therapy was initiated. We conclude that angioplasty should be considered in pediatric patients with acute occlusive limb ischemia, providing excellent immediate results to preserve the limb as well as the time to investigate the underlying causes. (orig.)

  6. Celiac disease manifesting as isolated cobalamin deficiency megaloblastic anemia: Case series and review

    Directory of Open Access Journals (Sweden)

    Vikram Sakaleshpur Kumar

    2014-01-01

    Full Text Available Celiac disease (CD is an immune-mediated enteropathy triggered by the ingestion of gluten in genetically susceptible individuals. It has been identified as one of the most common lifelong disorders on a worldwide basis. Enteropathy in CD is thought to be the final consequence of an abnormal immune reaction, showing features of both an innate and adaptive response to gluten prolamins. The clinical spectrum is wide, including cases with either typical intestinal or atypical extra intestinal features, or silent forms. Anemia has frequently been reported as the only manifestation or the most frequent extra-intestinal symptom of CD. The only available treatment consists in dietary exclusion of grains containing gluten.

  7. Pulmonary and Cerebral Infarcts Due to Secondary Thrombosis Risk of a Genetic Mutation: Life-threating Methylentetrahydrofolate Reductase (MTHFR Deficiency with Early Onset

    Directory of Open Access Journals (Sweden)

    Ianosi Edith Simona

    2016-06-01

    Full Text Available Methylentetrahydrofolate reductase (MTHFR is a key enzymatic component of the folate cycle, converting 5,10-methylentetrahydrofolate into 5-methylentetrahydrofolate. Severe MTHFR deficiency is a rare recessive disease leading to major hyperhomocysteinemia, homocystinuria, and progressive neurological distress within the two first decades of life.

  8. Obstrução arterial retiniana periférica associada com hiper-homocisteinemia: relato de caso Peripheral retinal arterial obstruction associated with hyperhomocysteinemia: case report

    Directory of Open Access Journals (Sweden)

    Alexandre Kazuo Misawa

    2008-10-01

    Full Text Available A hiperhomocisteinemia é fator de risco para fenômenos trombo-embólicos retinianos associados a quadro de oclusão vascular venosa e arterial. Descrevemos um paciente com obstrução arterial retiniana periférica, sem sinais de vasculite ativa, associada a proliferação de neovasos com tração vítreo-retiniana e hemorragia vítrea recidivante. O alto nível sérico de homocisteína decorrente de deficiência de vitamina B12 e ácido fólico, sem outras alterações na cascata da coagulação, inclusive com a pesquisa do fator V de Leiden, sugere que a hiper-homocisteinemia esteja diretamente ligada como fator causal deste quadro clínico. Embora apresentasse PPD elevado, o diagnóstico diferencial mais importante de doença de Eales foi menos considerado por ser diagnóstico de exclusão. O controle do quadro clínico foi feito com suplemento de vitaminas (B12 e ácido fólico e fotocoagulação retiniana periférica. A homocisteína plasmática total deve ser dosada em pacientes com obstrução vascular retiniana, já que a hiper-homocisteinemia é fator de risco modificável e de fácil tratamento por meio de dieta ou suplementação vitamínica.Hyperhomocysteinemia is a risk factor for thromboembolic events of the retina associated with vascular venous or arterial occlusion. We describe a patient with occlusion of the peripheral arteriolar network without active vasculitis, associated with neovascular proliferation, peripheral vitreous-retinal traction and relapsing vitreous hemorrhage. The high serum homocysteine level resulting from vitamin B12 and folic acid deficiency, without further changes in the coagulation cascade including the test for Leiden's Factor V, indicates hyperhomocysteinemia as a direct causal factor in this clinical condition. Despite a high PPD, Eales Disease, a major differential diagnosis, was not fully considered, since it is established by exclusion. The patient was treated with photocoagulation and vitamin

  9. Development of CHARMM-Compatible Force-Field Parameters for Cobalamin and Related Cofactors from Quantum Mechanical Calculations.

    Science.gov (United States)

    Pavlova, Anna; Parks, Jerry M; Gumbart, James C

    2018-02-13

    Corrinoid cofactors such as cobalamin are used by many enzymes and are essential for most living organisms. Therefore, there is broad interest in investigating cobalamin-protein interactions with molecular dynamics simulations. Previously developed parameters for cobalamins are based mainly on crystal structure data. Here, we report CHARMM-compatible force field parameters for several corrinoids developed from quantum mechanical calculations. We provide parameters for corrinoids in three oxidation states, Co 3+ , Co 2+ , and Co 1+ , and with various axial ligands. Lennard-Jones parameters for the cobalt center in the Co(II) and Co(I) states were optimized using a helium atom probe, and partial atomic charges were obtained with a combination of natural population analysis (NPA) and restrained electrostatic potential (RESP) fitting approaches. The Force Field Toolkit was used to optimize all bonded terms. The resulting parameters, determined solely from calculations of cobalamin alone or in water, were then validated by assessing their agreement with density functional theory geometries and by analyzing molecular dynamics simulation trajectories of several corrinoid proteins for which X-ray crystal structures are available. In each case, we obtained excellent agreement with the reference data. In comparison to previous CHARMM-compatible parameters for cobalamin, we observe a better agreement for the fold angle and lower RMSD in the cobalamin binding site. The approach described here is readily adaptable for developing CHARMM-compatible force-field parameters for other corrinoids or large biomolecules.

  10. Cobalamin Protection against Oxidative Stress in the Acidophilic Iron-oxidizing Bacterium Leptospirillum group II CF-1

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    Gloria Paz Levicán

    2016-05-01

    Full Text Available Members of the genus Leptospirillum are aerobic iron-oxidizing bacteria belonging to the phylum Nitrospira. They are important members of microbial communities that catalyze the biomining of sulfidic ores, thereby solubilizing metal ions. These microorganisms live under extremely acidic and metal-loaded environments and thus must tolerate high concentrations of reactive oxygen species. Cobalamin (vitamin B12 is a cobalt-containing tetrapyrrole cofactor involved in intramolecular rearrangement reactions and has recently been suggested to be an intracellular antioxidant. In this work, we investigated the effect of the exogenous addition of cobalamin on oxidative stress parameters in Leptospirillum group II strain CF-1. Our results revealed that the external supplementation of cobalamin reduces the levels of intracellular reactive oxygen species and the damage to biomolecules, and also stimulates the growth and survival of cells exposed to oxidative stress exerted by ferric ion, hydrogen peroxide, chromate and diamide. Furthermore, exposure of strain CF-1 to oxidative stress elicitors resulted in the transcriptional activation of the cbiA gene encoding CbiA of the cobalamin biosynthetic pathway. Altogether, these data suggest that cobalamin plays an important role in redox protection of Leptospirillum strain CF-1, supporting survival of this microorganism under extremely oxidative environmental conditions. Understanding the mechanisms underlying the protective effect of cobalamin against oxidative stress may help to develop strategies to make biomining processes more effective.

  11. Role of Ginkgo Biloba in Hyperhomocysteinemia Induced in Rats By L-Methionine and Gamma Irradiation

    International Nuclear Information System (INIS)

    Mansour, S.Z.

    2011-01-01

    The objective of this study is to evaluate the role of Ginkgo biloba in hyperhomocysteinemia and oxidative stress. Methionine was supplied orally to adult male albino rats with a dose of 1.7 g/kg/day during 4 weeks. Irradiation was applied to rats by whole body gamma irradiation with a dose of 2 Gy/week up to a total dose of 8 Gy. Ginkgo biloba (100 mg/kg/day) was supplemented orally to rats, daily, during the period of methionine administration and/or radiation exposure. Biochemical analysis in blood and brain tissues showed that methionine and/or gamma irradiation produced significant increases in homocysteine and acetylcholine esterase levels and significant decrease in nitric oxide (NO). Significant increase in malondialdehyde (MDA) with significant decreases in glutathione (GSH), glutathione peroxidase (GSH-Px), superoxide dismutase (SOD) and catalase levels were observed and alteration in plasma lipid profile was also recorded. Ginkgo biloba supplementation has significantly decreased homocysteine and acetylcholine esterase levels and increased NO while was associated with significant improvement of oxidative stress and lipid profile. It could be concluded that the protective effect of Gingko biloba against hyperhomocysteinemia and oxidative stress is attributed to its antioxidant and free radicals scavenging properties.

  12. Hyperhomocysteinemia is independently associated with albuminuria in the population-based CoLaus study

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    Paccaud Fred

    2011-09-01

    Full Text Available Abstract Background Increased serum levels of homocysteine and uric acid have each been associated with cardiovascular risk. We analyzed whether homocysteine and uric acid were associated with glomerular filtration rate (GFR and albuminuria independently of each other. We also investigated the association of MTHFR polymorphisms related to homocysteine with albuminuria to get further insight into causality. Methods This was a cross-sectional population-based study in Caucasians (n = 5913. Hyperhomocysteinemia was defined as total serum homocysteine ≥ 15 μmol/L. Albuminuria was defined as urinary albumin-to-creatinine ratio > 30 mg/g. Results Uric acid was associated positively with homocysteine (r = 0.246 in men and r = 0.287 in women, P P for trend P P = 0.004 were significantly associated with albuminuria, independently of hypertension and type 2 diabetes. The 2-fold higher risk of albuminuria associated with hyperhomocysteinemia was similar to the risk associated with hypertension or diabetes. MTHFR alleles related to higher homocysteine were associated with increased risk of albuminuria. Conclusions In the general adult population, elevated serum homocysteine and uric acid were associated with albuminuria independently of each other and of renal function.

  13. Association between hyperhomocysteinemia and metabolic syndrome with early carotid artery atherosclerosis: A cross-sectional study in middle-aged Chinese population.

    Science.gov (United States)

    Liu, Chengguo; Sun, Xiaohui; Lin, Hanli; Zheng, Ruizhi; Ruan, Liansheng; Sun, Zhanhang; Zhu, Yimin

    2018-03-21

    Homocysteine is a modifiable, independent risk factor for cardiovascular disease. The association between hyperhomocysteinemia and metabolic syndrome with the presence of early carotid artery atherosclerosis remains unknown in middle-aged Chinese adults. Chinese adults (n = 1607) of Han ethnicity, age 35 to 65 y, and living in their communities >2 y were surveyed. Hyperhomocysteinemia was defined as homocysteine concentrations >15 µmol/L. Carotid intima-media thickness and carotid plaque were examined by ultrasonography. All participants were classified into four groups by hyperhomocysteinemia and metabolic syndrome status. Participants with both hyperhomocysteinemia and metabolic syndrome had the highest levels of waist circumference and systolic blood pressure compared with the three other groups. The highest proportion of increased carotid intima-media thickness (61.3%) was in the subgroup of both hyperhomocysteinemia and metabolic syndrome. After adjustments for the covariates, the risk of increased carotid intima-media thickness was only significantly higher in the group with metabolic syndrome but without hyperhomocysteinemia (odds ratio: 1.47; 95% confidence interval, 1.13-1.93) compared with people without hyperhomocysteinemia and metabolic syndrome. Furthermore, statistically significant variances of prevalence of plaque among the four subgroups were not discovered. Our study demonstrated that metabolic syndrome had a strong effect on carotid intima-media thickness However, the increased homocysteine levels were not significantly associated with early carotid artery atherosclerosis in middle-aged Chinese people. Copyright © 2018 Elsevier Inc. All rights reserved.

  14. Correlation of Tc-99 m ethyl cysteinate dimer single-photon emission computed tomography and clinical presentations in patients with low cobalamin status.

    Science.gov (United States)

    Tu, Min-Chien; Lo, Chung-Ping; Chen, Ching-Yuan; Huang, Ching-Feng

    2015-12-03

    Cobalamin (Cbl) deficiency has been associated with various neuropsychiatric symptoms of different severities. While some studies dedicated in structural neuroimaging credibly address negative impact of low Cbl status, functional imaging reports are limited. We herein retrospectively review the correlation of Tc-99 m ethyl cysteinate dimer single-photon emission computed tomography (Tc-99 m-ECD SPECT) and clinical presentations among patients with low serum cobalamin (Cbl) status (Tc-99 m-ECD SPECT, and neuropsychological tests were reviewed. Dysexecutive syndrome (67 %), forgetfulness (50 %), attention deficits (42 %), and sleep disorders (33 %) constituted the major clinical presentations. All patients (100 %) had temporal hypoperfusion on the Tc-99 m-ECD SPECT. Five patients (42 %) had hypoperfusion restricted within temporal regions and deep nuclei; seven patients (58 %) had additional frontal hypoperfusion. In patients with hypoperfusion restricted within temporal regions and deep nuclei, psychiatric symptoms with spared cognition were their main presentations. Among patients with additional frontal hypoperfusion, six of seven patients (86 %) showed impaired cognitive performances (two of them were diagnosed as having dementia). Among ten patients who finished neuropsychological tests, abstract thinking (70 %) was the most commonly affected, followed by verbal fluency (60 %), short-term memory (50 %), and attention (50 %). Anxiety and sleep problems were the major clinically remarkable psychiatric features (33 % both). Four Tc-99 m-ECD SPECT follow-up studies were available; the degree and extent of signal reversal correlated with cognitive changes after Cbl replacement therapy. Our TC-99 m-ECD SPECT observations provide pivotal information of neurobiological changes within basal ganglia and fronto-temporal regions in conjunction with disease severity among patients with Cbl deficiency. Hypoperfusion within thalamus/basal ganglia and temporal regions may be

  15. Trans and cis influences and effects in cobalamins and in their simple models.

    Science.gov (United States)

    De March, Matteo; Demitri, Nicola; Geremia, Silvano; Hickey, Neal; Randaccio, Lucio

    2012-11-01

    The interligand interactions in coordination compounds have been principally interpreted in terms of cis and trans influences and effects, which can be defined as the ability of a ligand X to affect the bond of another ligand, cis or trans to X, to the metal. This review analyzes these effects/influences in cobalamins (XCbl) and their simple models cobaloximes, LCo(chel)X. Important properties of these complexes, such as geometry, stability, and reactivity, can be rationalized in terms of steric and electronic factors of the ligands. Experimental evidence of normal and inverse trans influence is described in alkylcobaloximes for the first time. The study of simple B(12) models has complemented that on the more complex cobalamins, with particular emphasis on the properties of the axial L-Co-X moiety. Some of the conclusions reached for the axial fragment of simple models have also been qualitatively detected in cobalamins and have furnished new insight into the as yet unestablished mechanism for the homolytic cleavage of the Co - C bond in the AdoCbl-based enzymes. Copyright © 2012 Elsevier Inc. All rights reserved.

  16. A proteomics study of hyperhomocysteinemia injury of the hippocampal neurons using iTRAQ.

    Science.gov (United States)

    Fang, Min; Wang, Jing; Yan, Han; Zhao, Yan-Xin; Liu, Xue-Yuan

    2014-11-01

    High levels of homocysteine, caused by abnormal methionine metabolism, can induce degeneration of mouse hippocampal neurons. iTRAQ™ technology has been widely used in the field of proteomics research and through employing this technology, the present study identified that hyperhomocysteinemia induced the downregulation of 52 proteins and upregulation of 44 proteins in the mouse hippocampus. Through gene ontology and pathway analysis, the upregulation of components of the cytoskeleton, actin, regulators of focal adhesion, calcium signaling pathways, tight junctions, ErbB and gonadotrophin‑releasing hormone signaling, leukocyte, transendothelial migration, propanoate and pyruvate metabolism, valine, leucine and isoleucine biosynthesis, synthesis and degradation of ketone bodies and benzoate degradation via CoA ligation pathway, was identified. It was additionally verified that tau protein was highly expressed in the hyperhomocysteinemic neurons. Further analysis revealed that tau network proteins played functional roles in homocysteine‑induced neuronal damage.

  17. A disulfide-stabilized conformer of methionine synthase reveals an unexpected role for the histidine ligand of the cobalamin cofactor

    Energy Technology Data Exchange (ETDEWEB)

    Datta, Supratim; Koutmos, Markos; Pattridge, Katherine A.; Ludwig, Martha L.; Matthews, Rowena G. (Michigan)

    2008-07-08

    B{sub 12}-dependent methionine synthase (MetH) from Escherichia coli is a large modular protein that is alternately methylated by methyltetrahydrofolate to form methylcobalamin and demethylated by homocysteine to form cob(I)alamin. Major domain rearrangements are required to allow cobalamin to react with three different substrates: homocysteine, methyltetrahydrofolate, and S-adenosyl-l-methionine (AdoMet). These same rearrangements appear to preclude crystallization of the wild-type enzyme. Disulfide cross-linking was used to lock a C-terminal fragment of the enzyme into a unique conformation. Cysteine point mutations were introduced at Ile-690 and Gly-743. These cysteine residues span the cap and the cobalamin-binding module and form a cross-link that reduces the conformational space accessed by the enzyme, facilitating protein crystallization. Here, we describe an x-ray structure of the mutant fragment in the reactivation conformation; this conformation enables the transfer of a methyl group from AdoMet to the cobalamin cofactor. In the structure, the axial ligand to the cobalamin, His-759, dissociates from the cobalamin and forms intermodular contacts with residues in the AdoMet-binding module. This unanticipated intermodular interaction is expected to play a major role in controlling the distribution of conformers required for the catalytic and the reactivation cycles of the enzyme.

  18. Hyperhomocysteinemia in patients with chronic kidney disease and its relationship with the functional status of the cardiovascular system

    OpenAIRE

    K. P. Postovitenko; I. A. Iliuk; S. V. Shevchuk; G. V. Bezsmertna; І. O. Bezsmertnyi; I. V. Kurylenko

    2017-01-01

    Chronic kidney disease (CKD) is an important medical, social and economic problem nowadays. Patients with CKD are known to have an increased risk of development and progression of cardiovascular diseases. However, the causes and pathogenesis of cardiovascular complications are not well understood. One of the recently recognized “non-traditional” risk factors for the increased development of cardiovascular pathology in severe stages of CKD is hyperhomocysteinemia (HHC). The article presents th...

  19. Mutations in THAP11 cause an inborn error of cobalamin metabolism and developmental abnormalities.

    Science.gov (United States)

    Quintana, Anita M; Yu, Hung-Chun; Brebner, Alison; Pupavac, Mihaela; Geiger, Elizabeth A; Watson, Abigail; Castro, Victoria L; Cheung, Warren; Chen, Shu-Huang; Watkins, David; Pastinen, Tomi; Skovby, Flemming; Appel, Bruce; Rosenblatt, David S; Shaikh, Tamim H

    2017-08-01

    CblX (MIM309541) is an X-linked recessive disorder characterized by defects in cobalamin (vitamin B12) metabolism and other developmental defects. Mutations in HCFC1, a transcriptional co-regulator which interacts with multiple transcription factors, have been associated with cblX. HCFC1 regulates cobalamin metabolism via the regulation of MMACHC expression through its interaction with THAP11, a THAP domain-containing transcription factor. The HCFC1/THAP11 complex potentially regulates genes involved in diverse cellular functions including cell cycle, proliferation, and transcription. Thus, it is likely that mutation of THAP11 also results in biochemical and other phenotypes similar to those observed in patients with cblX. We report a patient who presented with clinical and biochemical phenotypic features that overlap cblX, but who does not have any mutations in either MMACHC or HCFC1. We sequenced THAP11 by Sanger sequencing and discovered a potentially pathogenic, homozygous variant, c.240C > G (p.Phe80Leu). Functional analysis in the developing zebrafish embryo demonstrated that both THAP11 and HCFC1 regulate the proliferation and differentiation of neural precursors, suggesting important roles in normal brain development. The loss of THAP11 in zebrafish embryos results in craniofacial abnormalities including the complete loss of Meckel's cartilage, the ceratohyal, and all of the ceratobranchial cartilages. These data are consistent with our previous work that demonstrated a role for HCFC1 in vertebrate craniofacial development. High throughput RNA-sequencing analysis reveals several overlapping gene targets of HCFC1 and THAP11. Thus, both HCFC1 and THAP11 play important roles in the regulation of cobalamin metabolism as well as other pathways involved in early vertebrate development. © The Author 2017. Published by Oxford University Press. All rights reserved. For Permissions, please email: journals.permissions@oup.com.

  20. Anxiety-related behavior in hyperhomocysteinemia induced by methionine nutritional overload in rats: role of the brain oxidative stress.

    Science.gov (United States)

    Hrncic, Dragan; Mikić, Jelena; Rasic-Markovic, Aleksandra; Velimirović, Milica; Stojković, Tihomir; Obrenović, Radmila; Rankov-Petrović, Bojana; Šušić, Veselinka; Djuric, Dragan; Petronijević, Nataša; Stanojlovic, Olivera

    2016-10-01

    The aim of this study was to examine the effects of a methionine-enriched diet on anxiety-related behavior in rats and to determine the role of the brain oxidative status in these alterations. Adult male Wistar rats were fed from the 30th to 60th postnatal day with standard or methionine-enriched diet (double content comparing with standard diet: 7.7 g/kg). Rats were tested in open field and light-dark tests and afterwards oxidative status in the different brain regions were determined. Hyperhomocysteinemia induced by methionine-enriched diet in this study decreased the number of rearings, as well as the time that these animals spent in the center of the open field, but increased index of thigmotaxy. Oxidative status was selectively altered in the examined regions. Lipid peroxidation was significantly increased in the cortex and nc. caudatus of rats developing hyperhomocysteinemia, but unaltered in the hippocampus and thalamus. Based on the results of this research, it could be concluded that hyperhomocysteinemia induced by methionine nutritional overload increased anxiety-related behavior in rats. These proanxiogenic effects could be, at least in part, a consequence of oxidative stress in the rat brain.

  1. The functional cobalamin (vitamin B12)-intrinsic factor receptor is a novel complex of cubilin and amnionless

    DEFF Research Database (Denmark)

    Fyfe, John C; Madsen, Mette; Højrup, Peter

    2004-01-01

    Imerslund-Gräsbeck syndrome (I-GS, megaloblastic anemia 1) is an autosomal recessive disorder characterized by intestinal cobalamin (vitamin B(12)) malabsorption and proteinuria. I-GS-causing mutations are found in either of 2 genes encoding the epithelial proteins: cubilin and amnionless (AMN...... compartments. However, in cells cotransfected with AMN and the cubilin construct, cubilin trafficked to the cell surface and endosomes, and the cells exhibited IF-cobalamin endocytosis and lysosomal degradation of IF. These data indicate that cubilin and AMN are subunits of a novel cubilin/AMN (cubam) complex...

  2. Hiperhomocisteinemia na insuficiência renal crônica Hyperhomocysteinemia in chronic renal failure

    Directory of Open Access Journals (Sweden)

    Fabiana Baggio Nerbass

    2005-04-01

    Full Text Available A homocisteína é um aminoácido sulfurado proveniente do metabolismo da metionina, cujo acúmulo anormal no plasma é um fator de risco para doenças vasculares, tanto na população em geral como nos pacientes com insuficiência renal crônica. Nestes, a prevalência de indivíduos com hiperhomocisteinemia é bastante elevada, mesmo na fase não dialítica da doença, em que a função renal está diminuída, mas ainda não é necessário tratamento dialítico. O principal fator que parece estar implicado na elevação dos níveis de homocisteína nestes pacientes com insuficiência renal crônica é a perda da massa renal, já que esta exerce uma importante função no metabolismo desse aminoácido. O tratamento da hiperhomocisteinemia na população em geral consiste na suplementação com as vitaminas envolvidas no seu metabolismo (folato, B6 e B12. Porém, em pacientes com insuficiência renal crônica, este tratamento não é completamente eficaz, pois apesar de promover a redução dos níveis de homocisteína, não alcança a normalização dos mesmos na maioria dos pacientes. Este estudo compreende uma revisão da etiologia da hiperhomocisteinemia na insuficiência renal crônica, sua relação com as doenças vasculares, seus principais determinantes e as formas de tratamento.Homocysteine is a sulfur-containing amino acid derived from the metabolism of methionine, whose abnormal accumulation in plasma is a risk factor for vascular disease in the general population and in patients with chronic renal disease. In these patients, the prevalence of individuals with hyperhomocysteinemia is very high, even in the pre-dialysis stage of the disease. The main factor that seems to be implicated on the elevation of homocysteine levels in this population is the renal mass loss, considering that the kidney has an important role in the metabolism of such amino acid. The treatment of hyperhomocysteinemia consists on supplementation of the vitamins

  3. Recurrent pregnancy loss in polycystic ovary syndrome: role of hyperhomocysteinemia and insulin resistance.

    Directory of Open Access Journals (Sweden)

    Pratip Chakraborty

    Full Text Available Recurrent pregnancy loss (RPL in polycystic ovary syndrome (PCOS, which occurs in ∼50% of total pregnancies is a frequent obstetric complication. Among the several hypotheses, insulin resistance (IR, obesity and hyperhomocysteinemia (HHcy play significant role/s in RPL. This study was conducted to assess the link between elevated levels of homocysteine and IR in PCOS-associated women with RPL in Kolkata, India. A retrospective study was conducted of one hundred and twenty six PCOS women (<30 years who experienced two or more spontaneous abortions during the first trimester presenting to Institute of Reproductive Medicine (IRM in Kolkata during the period of March 2008 through February 2011. One hundred and seventeen non-PCOS subjects with matching age range were randomly chosen as controls. Incidence of HHcy and IR was 70.63% (n = 89 and 56.34% (n = 71, respectively, in RPL-affected PCOS population which was significantly higher (p<0.04; p<0.0001 when compared to the non-PCOS set (HHcy: 57.26%; IR: 6.83%. Rates of miscarriage were significantly higher (p<0.008; p<0.03 in hyperhomocysteinemia-induced miscarriage when compared to the normohomocysteinemic segment (PCOS: 70.63% vs.29.36% & non-PCOS: 57.26% vs. 42.73% along with the insulin resistant (p<0.04; p<0.0001 population (PCOS: 70.63% vs. 56.34% & non-PCOS: 57.26% vs. 6.83% in both groups. A probabilistic causal model evaluated HHcy as the strongest plausible factor for diagnosis of RPL. A probability percentage of 43.32% in the cases of HHcy- mediated RPL suggests its increased tendency when compared to IR mediated miscarriage (37.29%, further supported by ROC-AUC (HHcy: 0.778vs. IR: 0.601 values. Greater susceptibility towards HHcy may increase the incidence for miscarriage in women in India and highlights the need to combat the condition in RPL control programs in the subcontinent.

  4. Storage Pool Deficiencies

    Science.gov (United States)

    ... Deficiency Factor V Deficiency Combined FV & FVIII Deficiencies Factor VII Deficiency Factor X Deficiency Factor XI Deficiency Factor ... Deficiency Factor V Deficiency Combined FV & FVIII Deficiencies Factor VII Deficiency Factor X Deficiency Factor XI Deficiency Factor ...

  5. Opening of the blood-brain barrier before cerebral pathology in mild hyperhomocysteinemia.

    Directory of Open Access Journals (Sweden)

    Bryce C Rhodehouse

    Full Text Available Hyperhomocysteinemia (HHcy is a risk factor for cognitive impairment. The purpose of this study was to determine the temporal pattern of cerebral pathology in a mouse model of mild HHcy, because understanding this time course provides the basis for understanding the mechanisms involved. C57Bl/6 mice with heterozygous deletion cystathionine β-synthase (cbs (+/-; Het were used as a model of mild HHcy along with their wild-type littermates (cbs (+/+; WT. Mice were 'young' (5.3±0.2 months of age and 'old' (16.6±0.9 months of age. Blood-brain barrier (BBB permeability was quantified from Evans blue and sodium fluorescein extravasation. Microvascular architecture was assessed by z-stack confocal microscopy. Leukoaraiosis was measured from Luxol fast blue stained slides of paraffin brain sections. Inflammation was quantified using standard antibody-based immunohistochemical techniques. Cognitive function was assessed using the Morris water maze. BBB permeability was significantly greater in Het vs. WT mice at all ages (p<0.05. There were no differences in microvascular architecture among the groups. Compared with all other groups, old Het mice had significantly greater leukoaraiosis, inflammation in the fornix, and cognitive impairment (p<0.05. In mild HHcy, increased permeability of the BBB precedes the onset of cerebral pathology. This new paradigm may play a role in the progression of disease in HHcy.

  6. Effects of fisetin on hyperhomocysteinemia-induced experimental endothelial dysfunction and vascular dementia.

    Science.gov (United States)

    Hemanth Kumar, Boyina; Arun Reddy, Ravula; Mahesh Kumar, Jerald; Dinesh Kumar, B; Diwan, Prakash V

    2017-01-01

    This study was designed to investigate the effects of fisetin (FST) on hyperhomocysteinemia (HHcy)-induced experimental endothelial dysfunction (ED) and vascular dementia (VaD) in rats. Wistar rats were randomly divided into 8 groups: control, vehicle control, l-methionine, FST (5, 10, and 25 mg/kg, p.o.), FST-per se (25 mg/kg, p.o.), and donepezil (0.1 mg/kg, p.o.). l-Methionine administration (1.7 g/kg, p.o.) for 32 days induced HHcy. ED and VaD induced by HHcy were determined by vascular reactivity measurements, behavioral analysis using Morris water maze and Y-maze, along with a biochemical and histological evaluation of thoracic aorta and brain tissues. Administration of l-methionine developed behavioral deficits; triggered brain lipid peroxidation (LPO); compromised brain acetylcholinesterase activity (AChE); and reduced the levels of brain superoxide dismutase (SOD), brain catalase (CAT), brain reduced glutathione (GSH), and serum nitrite; and increased serum homocysteine and cholesterol levels. These effects were accompanied by decreased vascular NO bioavailability, marked intimal thickening of the aorta, and multiple necrotic foci in brain cortex. HHcy-induced alterations in the activities of SOD, CAT, GSH, AChE, LPO, behavioral deficits, ED, and histological aberrations were significantly attenuated by treatment with fisetin in a dose-dependent manner. Collectively, our results indicate that fisetin exerts endothelial and neuroprotective effects against HHcy-induced ED and VaD.

  7. Mechanisms of Hyperhomocysteinemia Induced Skeletal Muscle Myopathy after Ischemia in the CBS−/+ Mouse Model

    Directory of Open Access Journals (Sweden)

    Sudhakar Veeranki

    2015-01-01

    Full Text Available Although hyperhomocysteinemia (HHcy elicits lower than normal body weights and skeletal muscle weakness, the mechanisms remain unclear. Despite the fact that HHcy-mediated enhancement in ROS and consequent damage to regulators of different cellular processes is relatively well established in other organs, the nature of such events is unknown in skeletal muscles. Previously, we reported that HHcy attenuation of PGC-1α and HIF-1α levels enhanced the likelihood of muscle atrophy and declined function after ischemia. In the current study, we examined muscle levels of homocysteine (Hcy metabolizing enzymes, anti-oxidant capacity and focused on protein modifications that might compromise PGC-1α function during ischemic angiogenesis. Although skeletal muscles express the key enzyme (MTHFR that participates in re-methylation of Hcy into methionine, lack of trans-sulfuration enzymes (CBS and CSE make skeletal muscles more susceptible to the HHcy-induced myopathy. Our study indicates that elevated Hcy levels in the CBS−/+ mouse skeletal muscles caused diminished anti-oxidant capacity and contributed to enhanced total protein as well as PGC-1α specific nitrotyrosylation after ischemia. Furthermore, in the presence of NO donor SNP, either homocysteine (Hcy or its cyclized version, Hcy thiolactone, not only increased PGC-1α specific protein nitrotyrosylation but also reduced its association with PPARγ in C2C12 cells. Altogether these results suggest that HHcy exerts its myopathic effects via reduction of the PGC-1/PPARγ axis after ischemia.

  8. How common is vitamin B-12 deficiency?

    Science.gov (United States)

    Allen, Lindsay H

    2009-02-01

    In considering the vitamin B-12 fortification of flour, it is important to know who is at risk of vitamin B-12 deficiency and whether those individuals would benefit from flour fortification. This article reviews current knowledge of the prevalence and causes of vitamin B-12 deficiency and considers whether fortification would improve the status of deficient subgroups of the population. In large surveys in the United States and the United Kingdom, approximately 6% of those aged > or =60 y are vitamin B-12 deficient (plasma vitamin B-12 life. In developing countries, deficiency is much more common, starting in early life and persisting across the life span. Inadequate intake, due to low consumption of animal-source foods, is the main cause of low serum vitamin B-12 in younger adults and likely the main cause in poor populations worldwide; in most studies, serum vitamin B-12 concentration is correlated with intake of this vitamin. In older persons, food-bound cobalamin malabsorption becomes the predominant cause of deficiency, at least in part due to gastric atrophy, but it is likely that most elderly can absorb the vitamin from fortified food. Fortification of flour with vitamin B-12 is likely to improve the status of most persons with low stores of this vitamin. However, intervention studies are still needed to assess efficacy and functional benefits of increasing intake of the amounts likely to be consumed in flour, including in elderly persons with varying degrees of gastric atrophy.

  9. A general review on vitamin B12 deficiency with focus on the situation in Jordan

    International Nuclear Information System (INIS)

    Qutob, M. S.; Takruri, H. R.

    2011-01-01

    Vitamin B 12 (cobalamin) is an essential nutrient that is only obtained from foods of animal origin, such as meat, eggs and dairy products. Vitamin B 12 plays an important role in DNA synthesis and neurological function. Thus its deficiency can lead to several neurological symptoms such as memory loss, dizziness and in severe cases may lead to dementia. Many factors can cause or lead to vitamin B-1 2 deficiency. Among these are malabsorption, several gastron intestinal problems (i.e. celiac disease, Crobn's disease) and gastrointestinal surgeries. diagnosis of vitamin B-1 2 status depends commonly on serum vitamin B 12 which is nonspecific tool for the deficiency. Other more specific tests, which reflect true deficiency, include serum and urine methylmalonic aci de, total serum homocysteine and serum holotranscobalamin. Vitamin B 12 deficiency is a worldwide public health problem; epidemiological studies showed that its prevalence in industrialized countries ranges from 5-60% of the population depending on the used cutoff point of cobalamin level. In Jordan, many reports were published on vitamin B 12 deficiency. However, these reports gave different results of its prevalence ranging from 16-48% depending on the serum vitamin B 12 cutoff point used. A recent study showed a prevalence of true deficiency of 32.7% based on measuring both serum vitamin B 12 level and plasma methylmalonic acid. (authors).

  10. Severe vitamin B₁₂ deficiency in a 15-year-old boy: presentation with haemolysis and pancytopenia.

    Science.gov (United States)

    Keskin, Ebru Yılmaz; Keskin, Mahmut

    2015-05-14

    A 15-year-old boy on a vegetarian diet presented with severe macrocytic anaemia (haemoglobin, 5.1 g/dL; mean corpuscular volume, 116 fL) in addition to leucopenia and thrombocytopaenia (pancytopenia), icterus secondary to haemolysis and splenomegaly. Laboratory investigations revealed severe vitamin B12 (cobalamin) deficiency. Following cobalamin replacement therapy, the patient reported increased well-being, including appetite and weight gain, and his icterus resolved. In the follow-up laboratory examinations, leucocyte and platelet counts in addition to serum bilirubin and lactate dehydrogenase levels normalised. At the end of 2 months, laboratory findings, including haemoglobin level, were all within the normal range. We present this case as a reminder that severe vitamin B12 deficiency may present with findings mimicking acute leukaemia (pancytopenia and splenomegaly) and findings suggestive of pseudothrombotic microangiopathy. 2015 BMJ Publishing Group Ltd.

  11. Severe vitamin B12 deficiency in a 15-year-old boy: presentation with haemolysis and pancytopenia

    Science.gov (United States)

    Keskin, Ebru Yılmaz; Keskin, Mahmut

    2015-01-01

    A 15-year-old boy on a vegetarian diet presented with severe macrocytic anaemia (haemoglobin, 5.1 g/dL; mean corpuscular volume, 116 fL) in addition to leucopenia and thrombocytopaenia (pancytopenia), icterus secondary to haemolysis and splenomegaly. Laboratory investigations revealed severe vitamin B12 (cobalamin) deficiency. Following cobalamin replacement therapy, the patient reported increased well-being, including appetite and weight gain, and his icterus resolved. In the follow-up laboratory examinations, leucocyte and platelet counts in addition to serum bilirubin and lactate dehydrogenase levels normalised. At the end of 2 months, laboratory findings, including haemoglobin level, were all within the normal range. We present this case as a reminder that severe vitamin B12 deficiency may present with findings mimicking acute leukaemia (pancytopenia and splenomegaly) and findings suggestive of pseudothrombotic microangiopathy. PMID:25976204

  12. Preconception Screening for Gene Polymorphisms Associated with Thrombophilia and Hyperhomocysteinemia Risk in Healthy Young Women

    Directory of Open Access Journals (Sweden)

    Elena Yu. Glotova

    2013-09-01

    Full Text Available The frequency characteristics of the gene polymorphisms (FVL G1691A, FII G20210A, MTHFR C677T, MTHFR A1298C, MTRR A66G associated with thrombophilia, hyperhomocysteinemia risk and different perinatal or pregnancy complications were studied. This examination was conducted among 130 planned-pregnancy healthy young women aged between 19 and 29 years. A gene mutation analysis was performed using a real-time polymerase chain reaction (real-time PCR. Factor V Leiden (FVL G1691A and prothrombin gene (FII G20210A mutations were not identified in the women surveyed. The frequency of the occurrence of the heterozygous FVL 1691G/A genotype associated with the risk of thrombosis during pregnancy was very low in these women (0.8%. The frequency of the MTHFR (methylenetetrahydrofolate reductase 1298C/С mutant genotype was 11.5%, MTHFR 677T/Т – 5.4%, and MTRR (methionine synthase reductase 66G/G – 31.5%. A combination of the MTHFR 677TT/1298CC and MTHFR 677TТ/MTRR 66GG mutant genotypes, which significantly increased the risk of pregnancy loss and neural tube defects, were found to occur in 0.8% of the cases.We concluded that selective thrombophilia screening (FVL G1691A and FII G20210A based on prior personal and/or family history of venous thromboembolism was more cost-effective than a universal preconception screening in all planning pregnancy women. However, in order to decrease the risk of congenital anomalies and pregnancy complications associated with folate dependent homocysteine metabolism, preconception care should include folate supplementation

  13. Hyperhomocysteinemia - an additional risk factor of thrombosis in systemic lupus erythematosus and antiphospholipid syndrome

    Directory of Open Access Journals (Sweden)

    I. E. Shirokova

    2003-01-01

    Full Text Available Objective. To assess homocystein (HC level in systemic lupus erythematosus (SLE with antiphospholipid syndrome (APS and its relation to thrombosis development and blood lipide spectrum disturbances. Material and methods. 32 pts (12 male and 20 female with mean age 36 12 years and mean disease duration 13 11 years were included. 8 pts had SLE without APS, 13 - SLE with APS and 11 - primary APS (PAPS. All pts were divided into 2 groups depending on blood HC level. 26 pts with HC level more than 12 mcg/d! were included In group 1 and 6 pts with HC level less than 12 mcg/dl - in group 2. HC level was measured with high efficacious liquid chromatography (HELC. Lipid-protein blood spectrum was assessed in all pts. Results. Elevated HC level was revealed in 26 from 32 pts: in 16 with SLE (including 12 pts with APS and in 10 with PAPS. HC concentration did not depend on APS presence, but frequence of hyperhomocysteinemia (HHC significantly associated with APS and thrombotic complications. 20 from 26 (76,9% pts with HHC had thrombosis history. Only I from 6 (16,7% pts with normal HC level had thrombosis history (exact Fisher test p=0,02. HC level did not depend on age and sex. Changes of blood lipid-protein indices were revealed in most pts. Lipid spectrum disturbances were confined largely to cholesterol elevation due to increase of atherogenic lipoproteins cholesterol. Only 22% of pts showed decrease of antiatherogenic lipoproteins concentration. Bblood lipid-protein spectrum indices did not depend on HC level. Conclusion. HHC is present in 84,6% of pts with APS (primary and secondary. In pts with APS HHC is more frequent than in pts without APS. HHC is associated with thrombotic complications. HHC and lipid-protein spectrum disturbances are independent risk factors of thrombotic complications in pts with SLE and APS.

  14. Homocysteine Lowering by Folate-Rich Diet or Pharmacological Supplementations in Subjects with Moderate Hyperhomocysteinemia

    Directory of Open Access Journals (Sweden)

    Lorenza Mistura

    2013-05-01

    Full Text Available To compare the efficacy of a diet rich in natural folate and of two different folic acid supplementation protocols in subjects with “moderate” hyperhomocysteinemia, also taking into account C677T polymorphism of 5,10-methylenetetrahydrofolate reductase (MTHFR gene. Subjects/Methods: We performed a 13 week open, randomized, double blind clinical trial on 149 free living persons with mild hyperhomocyteinemia, with daily 200 μg from a natural folate-rich diet, 200 μg [6S]5-methyltetrahydrofolate (5-MTHF, 200 μg folic acid or placebo. Participants were stratified according to their MTHFR genotype. Results: Homocysteine (Hcy levels were reduced after folate enriched diet, 5-MTHF or folic acid supplementation respectively by 20.1% (p < 0.002, 19.4% (p < 0.001 and 21.9% (p < 0.001, as compared to baseline levels and significantly as compared to placebo (p < 0.001, p < 0.002 and p < 0.001, respectively for enriched diet, 5-MTHF and folic acid. After this enriched diet and the folic acid supplementation, Hcy in both genotype groups decreased approximately to the same level, with higher percentage decreases observed for the TT group because of their higher pre-treatment value. Similar results were not seen by genotype for 5-MTHF. A significant increase in RBC folate concentration was observed after folic acid and natural folate-rich food supplementations, as compared to placebo. Conclusions: Supplementation with natural folate-rich foods, folic acid and 5-MTHF reached a similar reduction in Hcy concentrations.

  15. Metagenomic and Metatranscriptomic Analyses Reveal the Structure and Dynamics of a Dechlorinating Community Containing Dehalococcoides mccartyi and Corrinoid-Providing Microorganisms under Cobalamin-Limited Conditions

    Energy Technology Data Exchange (ETDEWEB)

    Men, Yujie; Yu, Ke; Bælum, Jacob; Gao, Ying; Tremblay, Julien; Prestat, Emmanuel; Stenuit, Ben; Tringe, Susannah G.; Jansson, Janet; Zhang, Tong; Alvarez-Cohen, Lisa; Liu, Shuang-Jiang

    2017-02-10

    ABSTRACT

    The aim of this study is to obtain a systems-level understanding of the interactions betweenDehalococcoidesand corrinoid-supplying microorganisms by analyzing community structures and functional compositions, activities, and dynamics in trichloroethene (TCE)-dechlorinating enrichments. Metagenomes and metatranscriptomes of the dechlorinating enrichments with and without exogenous cobalamin were compared. Seven putative draft genomes were binned from the metagenomes. At an early stage (2 days), more transcripts of genes in theVeillonellaceaebin-genome were detected in the metatranscriptome of the enrichment without exogenous cobalamin than in the one with the addition of cobalamin. Among these genes, sporulation-related genes exhibited the highest differential expression when cobalamin was not added, suggesting a possible release route of corrinoids from corrinoid producers. Other differentially expressed genes include those involved in energy conservation and nutrient transport (including cobalt transport). The most highly expressed corrinoidde novobiosynthesis pathway was also assigned to theVeillonellaceaebin-genome. Targeted quantitative PCR (qPCR) analyses confirmed higher transcript abundances of those corrinoid biosynthesis genes in the enrichment without exogenous cobalamin than in the enrichment with cobalamin. Furthermore, the corrinoid salvaging and modification pathway ofDehalococcoideswas upregulated in response to the cobalamin stress. This study provides important insights into the microbial interactions and roles played by members of dechlorinating communities under cobalamin-limited conditions.

    IMPORTANCEThe key

  16. Hemolytic uremic syndrome (HUS) secondary to cobalamin C (cblC) disorder.

    Science.gov (United States)

    Sharma, Ajay P; Greenberg, Cheryl R; Prasad, Asuri N; Prasad, Chitra

    2007-12-01

    Diarrhea-positive hemolytic uremic syndrome (HUS) is a common cause of acute renal failure in children. Diarrhea-negative (D-), or atypical HUS, is etiologically distinct. A Medline search identified seven previously reported D- cases of HUS secondary to cobalamin C (cblC) disease presenting in infancy. An infantile presentation is reported to be associated with a high mortality rate (6/7 cases). We describe the results of a 5-year longitudinal follow-up in a child diagnosed with D- HUS secondary to cblC disease in infancy. Mutation analysis in this patient identified homozygosity for the 271 dupA mutation (c.271 dupA) in the cblC MMACHC gene. We briefly review the published experience in cblC-associated HUS to highlight the clinical characteristics of this uncommon, but potentially treatable, condition.

  17. Electron addition to alkyl cobalamins, coenzyme B12 and vitamin B12

    International Nuclear Information System (INIS)

    Rao, D.N.R.; Symons, M.C.R.

    1983-01-01

    Exposure of dilute solutions of methyl and ethyl cobalamins and coenzyme B 12 in dilute solutions (D 2 O+CD 3 OD) to 60 Co #betta#-rays at 77 K gave a single broad feature in the free-spin region assigned to electron-capture species with the excess electron largely confined to a π* corrin orbital. On warming above 77 K the methyl derivative gave a novel species with spectral features characteristic of an unpaired electron in the Co(dsub(x 2 -y 2 )) orbital. The other two substrates gave spectra due to Cosup(II)Bsub(12r) both on warming and after photolyses with visible light. The acetyl derivative gave an electron-capture species whose e.s.r. spectrum was characteristic of an electron in the Co(dsub(z 2 )) orbital, which on warming above 77 K changed to the normal Cosup(II)Bsub(12r) spectrum. The cyano derivative (vitamin B 12 ) gave electron addition into the Co(dsub(z 2 )) orbital, as evidenced by the large hyperfine coupling to 13 C from 13 CN ligands. On annealing, cyanide ions were lost irreversibly, Bsub(12r) being detected by e.s.r. spectroscopy. In contrast, the dicyano derivative on electron addition at 77 K gave a species containing only one 13 CN ligand. Hence in this case one CN - ligand was lost at 77 K, with no return of the dimethylbenzimidazole ligand. These results are discussed in terms of a new mechanism for electron-addition to alkyl cobalamins. (author)

  18. An Amoebal Grazer of Cyanobacteria Requires Cobalamin Produced by Heterotrophic Bacteria.

    Science.gov (United States)

    Ma, Amy T; Beld, Joris; Brahamsha, Bianca

    2017-05-15

    Amoebae are unicellular eukaryotes that consume microbial prey through phagocytosis, playing a role in shaping microbial food webs. Many amoebal species can be cultivated axenically in rich media or monoxenically with a single bacterial prey species. Here, we characterize heterolobosean amoeba LPG3, a recent natural isolate, which is unable to grow on unicellular cyanobacteria, its primary food source, in the absence of a heterotrophic bacterium, a Pseudomonas species coisolate. To investigate the molecular basis of this requirement for heterotrophic bacteria, we performed a screen using the defined nonredundant transposon library of Vibrio cholerae , which implicated genes in corrinoid uptake and biosynthesis. Furthermore, cobalamin synthase deletion mutations in V. cholerae and the Pseudomonas species coisolate do not support the growth of amoeba LPG3 on cyanobacteria. While cyanobacteria are robust producers of a corrinoid variant called pseudocobalamin, this variant does not support the growth of amoeba LPG3. Instead, we show that it requires cobalamin that is produced by the Pseudomonas species coisolate. The diversity of eukaryotes utilizing corrinoids is poorly understood, and this amoebal corrinoid auxotroph serves as a model for examining predator-prey interactions and micronutrient transfer in bacterivores underpinning microbial food webs. IMPORTANCE Cyanobacteria are important primary producers in aquatic environments, where they are grazed upon by a variety of phagotrophic protists and, hence, have an impact on nutrient flux at the base of microbial food webs. Here, we characterize amoebal isolate LPG3, which consumes cyanobacteria as its primary food source but also requires heterotrophic bacteria as a source of corrinoid vitamins. Amoeba LPG3 specifically requires the corrinoid variant produced by heterotrophic bacteria and cannot grow on cyanobacteria alone, as they produce a different corrinoid variant. This same corrinoid specificity is also

  19. Paracellular transport of avidin saturated or not with biotinylated cobalamin through Caco-2 cell epithelium monolayer.

    Science.gov (United States)

    Guy, M; Pons, L; Namour, F; de Nonancourt, M; Michalski, J C; Hatier, R; Guéant, J L

    2001-01-01

    The cationic charge of molecules may promote their uptake across epithelia, which are rich in brush border anionic sites. The transport of unsaturated avidin and avidin saturated with a biotinylated compound was investigated across Caco-2 adenocarcinoma cell with fetal enterocyte phenotype. The unsaturated avidin and avidin saturated with either biotin or a biotinyl-cobalamin conjugate (biotinyl-Cbl) were iodinated to follow their transport through the cell monolayer. Their apparent permeability coefficient (Papp) and transepithelial pathway were determined and compared to those for control radiolabeled markers [3H]-mannitol, [125I]-beta-lactoglobulin and [57Co]-cobalamin/intrinsic factor (Cbl/IF). The Papp of [125I]-avidin estimated at 2.8 x 10(-7) +/- 0.08 cm/s was close to that for mannitol that uses paracellular pathway. The binding of biotin or biotin conjugate to avidin enhanced its tetrameric conformation. The Papp for [125I]-avidin/biotin and [125I]- avidin/biotinyl-Cbl were respectively increased by 2-fold, compared to that for [125I]-avidin and 4-fold, compared to that for [125I]-beta-lactoglobulin and [54Co]-Cbl/IF. The protein was not accumulated in the cell and was found in intact form in the basolateral side, after its transport across the monolayer. Chloroquine (0.66 micromol/ml) did not significantly decrease the Papp for [125I]-avidin/biotinyl-Cbl. Conversely it decreased by 80% the Papp for Cbl/IF, that uses transepithelial pathway. Avidin (either saturated or not with biotin and biotinyl-Cbl) was able to cross the monolayer of Caco-2 cell line through a paracellular pathway. This study pointed out the interest for using this protein as a shuttle for increasing the transport rate of biotinylated compounds through fetal epithelial barriers. Copyright 2001 S. Karger AG, Basel

  20. Reversible Vitamin B12 Deficiency Presenting with Acute Dementia, Paraparesis, and Normal Hemoglobin

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    Hani Almoallim

    2016-01-01

    Full Text Available Vitamin B12 is essential for neurological function and its deficiency is associated with many neuropsychiatric disorders. We report the case of a previously healthy 53-year-old male patient presenting with delirium and multiple neurological findings. Complete blood analysis indicated megaloblastic anemia. All infectious causes were excluded owing to negative cultures (blood and urine. Tests for human immunodeficiency virus, syphilis, and toxoplasma were also negative. Metabolic workup showed severe vitamin B12 deficiency, decreased reticulocyte count, and increased direct bilirubin and lactate dehydrogenase. Intramuscular injection of cobalamin was started, and the patient showed significant improvement.

  1. Hyperhomocysteinemia potentiates diabetes-impaired EDHF-induced vascular relaxation: Role of insufficient hydrogen sulfide

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    Zhongjian Cheng

    2018-06-01

    Full Text Available Insufficient hydrogen sulfide (H2S has been implicated in Type 2 diabetic mellitus (T2DM and hyperhomocysteinemia (HHcy-related cardiovascular complications. We investigated the role of H2S in T2DM and HHcy-induced endothelial dysfunction in small mesenteric artery (SMA of db/db mice fed a high methionine (HM diet. HM diet (8 weeks induced HHcy in both T2DM db/db mice and non-diabetic db/+ mice (total plasma Hcy: 48.4 and 31.3 µM, respectively, and aggravated the impaired endothelium-derived hyperpolarization factor (EDHF-induced endothelium-dependent relaxation to acetylcholine (ACh, determined by the presence of eNOS inhibitor N(ω-nitro-L-arginine methyl ester (L-NAME and prostacyclin (PGI2 inhibitor indomethacin (INDO, in SMA from db/db mice but not that from db/+ mice. A non-selective Ca2+-active potassium channel (KCa opener NS309 rescued T2DM/HHcy-impaired EDHF-mediated vascular relaxation to ACh. EDHF-induced relaxation to ACh was inhibited by a non-selective KCa blocker TEA and intermediate-conductance KCa blocker (IKCa Tram-34, but not by small-conductance KCa (SKCa blocker Apamin. HHcy potentiated the reduction of free sulfide, H2S and cystathionine γ-lyase protein, which converts L-cysteine to H2S, in SMA of db/db mice. Importantly, a stable H2S donor DATS diminished the enhanced O2- production in SMAs and lung endothelial cells of T2DM/HHcy mice. Antioxidant PEG-SOD and DATS improved T2DM/HHcy impaired relaxation to ACh. Moreover, HHcy increased hyperglycemia-induced IKCa tyrosine nitration in human micro-vascular endothelial cells. EDHF-induced vascular relaxation to L-cysteine was not altered, whereas such relaxation to NaHS was potentiated by HHcy in SMA of db/db mice which was abolished by ATP-sensitive potassium channel blocker Glycolamide but not by KCa blockers. Conclusions: Intermediate HHcy potentiated H2S reduction via CSE-downregulation in microvasculature of T2DM mice. H2S is justified as an EDHF. Insufficient H2S

  2. Absorption of food cobalamins assessed by the double isotope method in healthy volunteers and in patients with chronic diarrhoea

    International Nuclear Information System (INIS)

    Kittang, B.; Hamborg, B.; Schjoensby, H.

    1985-01-01

    To make a food preparation containing radioactively labelled cobalamins, rabbits were given repeated injections with 57 Co-labelled cyanocobalamin. The liver was removed, homogenized and fried for one min. or boiled for 30 min. Of the radioactivity in the fried homogenate, 41.7% was recovered in the centrifuged supernatant compared with 50.8% in the boiled homogenate. The radioactivity in the supernatants had a molecular size close to that of free 57 Co-labelled cyanocobalamin. 42% of the radioactivity in the whole homogenate had been incorporated into 5-deoxyadenosyl-, 10% into methyl-and 16.5% into hydroxy-cobalamin. To assess the validity of a double-isotope method for measuring the intestinal absorption of doses of 57 Co-labelled liver cobalamins, 51 CrCl 3 was used as a non-absorbable marker. In 14 healthy volunteers the correlation coefficient between the absorption measured by the double-isotope technique and the faecal excretion test was highly significant (r = 0.96, p 57 Co/ 51 Cr ratio in successive stool collections. In 11 patients with chronic diarrhoea there was a significant correlation between the absorption measured by the double-isotope technique and the faecal excretion test (r = 0.92, p 57 / 51 Cr ratio in successive stool collections

  3. Effect of intramuscular injection of butafosfan and cobalamin on the quality of Fresh and Cooled Stallion Semen

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    Nicolás Cazales Penino

    2015-08-01

    Full Text Available The use of butafosfan in combination with cobalamin modulates many cellular metabolic functions in several species. Its use enhances productive and reproductive performance and reduces stress responses in animals. Despite all these attributes, so far there have been no controlled studies to evaluate the effects of butafosfan and cobalamin on the quality of stallion semen. The purpose of this study was to evaluate the action of butafosfan in combination with cobalamin on the quality of fresh and cooled stallion semen. Four healthy stallions were kept in the same place and under the same management conditions during the entire experiment. Stallions were randomly assigned to two treatment groups in a 2x2 crossover design. Group A stallions were treated with an intramuscular injection of butafosfan twice a week for 80 days, while group B did not receive any treatment. After that, both groups were not treated for another 80 days allowing a washout period for the treated group. Then, the groups were reversed, and group B was treated with butafosfan and group A acted as the control for another 80 days. Semen was collected twice a week, diluted in skim milk and evaluated for total sperm count, total and progressive sperm motility, membrane integrity (CFDA/PI staining and membrane functionality (HOS test at 0 and 24 hours after preservation at 5ºC. Data were analyzed by comparing the values obtained from the treated stallions between the 60th and 84th days of treatment and the values obtained from the same stallion during the control period. The ejaculates of the washout period and between days 1 and 63 of treatment were not considered. A total of 85 ejaculates were analyzed by one-way ANOVA. Means were compared by the Tukey test at the 5% level of significance. No significant differences were observed in fresh and cooled semen regarding the total sperm count, total motility, progressive motility, membrane integrity and membrane functionality in the

  4. MRI of the spine in cobalamin deficiency: the value of examining both spinal cord and bone marrow

    Energy Technology Data Exchange (ETDEWEB)

    Duprez, T.P. [Dept. of Diagnostic Imaging, Cliniques Univ. Saint-Luc, Univ. Catholique de Louvain, Brussls (Belgium); Gille, M. [Clinique Sainte-Elisabeth, Brussels (Belgium). Dept. of Neurology; Vande Berg, B.C. [Dept. of Diagnostic Imaging, Cliniques Univ. Saint-Luc, Univ. Catholique de Louvain, Brussls (Belgium); Malghem, J. [Dept. of Diagnostic Imaging, Cliniques Univ. Saint-Luc, Univ. Catholique de Louvain, Brussls (Belgium); Grandin, C.B. [Dept. of Diagnostic Imaging, Cliniques Univ. Saint-Luc, Univ. Catholique de Louvain, Brussls (Belgium); Michel, P. [Dept. of Pathology, Brussels (Belgium); Ghariani, S. [Clinique Sainte-Elisabeth, Brussels (Belgium). Dept. of Neurology; Maldague, B.E. [Dept. of Diagnostic Imaging, Cliniques Univ. Saint-Luc, Univ. Catholique de Louvain, Brussls (Belgium)

    1996-08-01

    We observed a case of pernicious anaemia in which MRI of the spine demonstrated both intrinsic lesions of the spinal cord and abnormal signal in the bone marrow. The latter resolved with replacement therapy. Only partial recovery of the cord lesions was observed. (orig.)

  5. MRI of the spine in cobalamin deficiency: the value of examining both spinal cord and bone marrow

    International Nuclear Information System (INIS)

    Duprez, T.P.; Gille, M.; Malghem, J.; Grandin, C.B.; Michel, P.; Ghariani, S.

    1996-01-01

    We observed a case of pernicious anaemia in which MRI of the spine demonstrated both intrinsic lesions of the spinal cord and abnormal signal in the bone marrow. The latter resolved with replacement therapy. Only partial recovery of the cord lesions was observed. (orig.)

  6. Monitoring the effectiveness of the natural anticoagulant sulodexide in pregnant women with autoimmune hyperthyroidism on the background of hyperhomocysteinemia

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    A.Yu. Scherbakov

    2017-04-01

    Full Text Available According to modern concepts, the occurrence of complications in utero-placental pool during pregnancy is a common cause of primary placental insufficiency, severe forms of late gestosis, recurrent miscarriage. It is obvious that the study of the nature of violations in the hemostatic system during pregnancy and the development of methods for timely correction will be the prevention of many obstetric diseases. Among the factors that affect hemostasis, thyroid hormones occupy a special place, they are able to influence not only the functional activity of platelets, but also adjust the intensity of the plasma and tissue fibrinolysis. Oppression of fibrinolytic activity is one of the pathogenetic factors of thrombosis development. The aim – to study the efficacy of natural anticoagulant sulodexide in pregnant women with autoimmune hyperthyroidism on the background of hyperhomocysteinemia. Materials and methods. The study involved 34 pregnant women with autoimmune hyperthyroidism complicated by hyperhomocysteinemia. A control group comprised 29 somatically healthy pregnant women. General clinical examination was carried out, the main indicators of all the links of the hemostatic system and the level of homocysteine were determined. Results. We determined that the main group of pregnant is characterized with chronometric and structural hypercoagulation, which manifests itself in the form of subclinical syndrome of disseminated intravascular coagulation, leading to complications of pregnancy, childbirth and the pathological condition of the fetus. Addition of anticoagulant sulodexide to the standard treatment led to the significant change in indices of all the components of hemostasis in pregnant women of the main group, in particular normalization of the total capacity of the coagulation and fibrinolytic systems. Decrease in activity of intravascular coagulation and platelet aggregation, the level of homocysteine was marked. Clinical indicators of

  7. Iodine Deficiency

    Science.gov (United States)

    ... Fax/Phone Home » Iodine Deficiency Leer en Español Iodine Deficiency Iodine is an element that is needed ... world’s population remains at risk for iodine deficiency. Iodine Deficiency FAQs WHAT IS THE THYROID GLAND? The ...

  8. Vitamin B12 Deficiency and the Role of Gender: A Cross-Sectional Study of a Large Cohort.

    Science.gov (United States)

    Margalit, Ili; Cohen, Eytan; Goldberg, Elad; Krause, Ilan

    2018-01-01

    Vitamin B12 deficiency is associated with hematological, neurological, and cardiovascular consequences. Epidemiologic data on these related illnesses indicate gender differences. A cross-sectional study was designed to examine gender differences in vitamin B12 deficiency among a healthy population. Data from healthy individuals aged 18-65, who were provided with a routine medical evaluation during 2000-2014, were retrieved from the medical charts. Individuals with background illnesses and those who had used medications or nutritional supplements were excluded. Vitamin B12 deficiency was defined by 2 cutoff values (206 and 140 pmol/L). The multivariate analysis was adjusted for age, body mass index, estimated glomerular filtration rate, hyperhomocysteinemia, folate deficiency, albumin, and transferrin saturation. Sensitivity analyses were implemented by excluding individuals with anemia, hyperhomocysteinemia, or folate deficiency and by age stratification. In all, 7,963 individuals met the inclusion criteria. Serum vitamin B12 mean levels were 312.36 and 284.31 pmol/L for women and men respectively (p variations are therefore hypothesized to play a role. © 2018 S. Karger AG, Basel.

  9. The Extracellular Heme-binding Protein HbpS from the Soil Bacterium Streptomyces reticuli Is an Aquo-cobalamin Binder*

    Science.gov (United States)

    Ortiz de Orué Lucana, Darío; Fedosov, Sergey N.; Wedderhoff, Ina; Che, Edith N.; Torda, Andrew E.

    2014-01-01

    The extracellular protein HbpS from Streptomyces reticuli interacts with iron ions and heme. It also acts in concert with the two-component sensing system SenS-SenR in response to oxidative stress. Sequence comparisons suggested that the protein may bind a cobalamin. UV-visible spectroscopy confirmed binding (Kd = 34 μm) to aquo-cobalamin (H2OCbl+) but not to other cobalamins. Competition experiments with the H2OCbl+-coordinating ligand CN− and comparison of mutants identified a histidine residue (His-156) that coordinates the cobalt ion of H2OCbl+ and substitutes for water. HbpS·Cobalamin lacks the Asp-X-His-X-X-Gly motif seen in some cobalamin binding enzymes. Preliminary tests showed that a related HbpS protein from a different species also binds H2OCbl+. Furthermore, analyses of HbpS-heme binding kinetics are consistent with the role of HbpS as a heme-sensor and suggested a role in heme transport. Given the high occurrence of HbpS-like sequences among Gram-positive and Gram-negative bacteria, our findings suggest a great functional versatility among these proteins. PMID:25342754

  10. [Age-related changes in biogenic amine content and oxidative stress profile in the rat hypothalamus in hyperhomocysteinemia].

    Science.gov (United States)

    Milyutina, Yu P; Pustygina, A V; Zaloznyaya, I V; Arutjunyan, A V

    2016-01-01

    The article presents a detailed analysis of correlations between the content of a variety of biogenic amines in the hypothalamic structures responsible for the luteinizing hormone releasing hormone synthesis and secretion (the medial preoptic area and median eminence) and such independent factors as total L-homocysteine plasma level elevation induced by L-methionine loading and aging. Both a nature and a pattern of changes in oxidative stress profile were evaluated. It was shown that ageing, when compared to hyperhomocysteinemia, is a determining factor influencing biogenic amine content in the studied hypothalamic structures. Unlike antioxidant defense system profile, considerable changes in macromolecule oxidative modification were not found, which evidences a balanced activity of pro- and antioxidant systems in the hypothalamus.

  11. Late Onset Cobalamin Disorder and Hemolytic Uremic Syndrome: A Rare Cause of Nephrotic Syndrome

    Directory of Open Access Journals (Sweden)

    Gianluigi Ardissino

    2017-01-01

    Full Text Available Hemolytic uremic syndrome (HUS is an unrare and severe thrombotic microangiopathy (TMA caused by several pathogenetic mechanisms among which Shiga toxin-producing Escherichia coli infections and complement dysregulation are the most common. However, very rarely and particularly in neonates and infants, disorders of cobalamin metabolism (CblC can present with or be complicated by TMA. Herein we describe a case of atypical HUS (aHUS related to CblC disease which first presented in a previously healthy boy at age of 13.6 years. The clinical picture was initially dominated by nephrotic range proteinuria and severe hypertension followed by renal failure. The specific treatment with high dose of hydroxycobalamin rapidly obtained the remission of TMA and the complete recovery of renal function. We conclude that plasma homocysteine and methionine determinations together with urine organic acid analysis should be included in the diagnostic work-up of any patient with TMA and/or nephrotic syndrome regardless of age.

  12. A Rich Man, Poor Man Story of S-Adenosylmethionine and Cobalamin Revisited.

    Science.gov (United States)

    Bridwell-Rabb, Jennifer; Grell, Tsehai A J; Drennan, Catherine L

    2018-06-20

    S-adenosylmethionine (AdoMet) has been referred to as both "a poor man's adenosylcobalamin (AdoCbl)" and "a rich man's AdoCbl," but today, with the ever-increasing number of functions attributed to each cofactor, both appear equally rich and surprising. The recent characterization of an organometallic species in an AdoMet radical enzyme suggests that the line that differentiates them in nature will be constantly challenged. Here, we compare and contrast AdoMet and cobalamin (Cbl) and consider why Cbl-dependent AdoMet radical enzymes require two cofactors that are so similar in their reactivity. We further carry out structural comparisons employing the recently determined crystal structure of oxetanocin-A biosynthetic enzyme OxsB, the first three-dimensional structural data on a Cbl-dependent AdoMet radical enzyme. We find that the structural motifs responsible for housing the AdoMet radical machinery are largely conserved, whereas the motifs responsible for binding additional cofactors are much more varied.

  13. Hyperhomocysteinemia, coronary heart disease, and diabetes mellitus as predicted by various definitions for metabolic syndrome in a hypertensive Saudi population

    International Nuclear Information System (INIS)

    Al-Daghri, Nasser M.

    2007-01-01

    From the emergence of different definitions of metabolic syndrome (MS) we aim to determine the prevalence of such a condition among hypertensive Saudi population and to identify which definition can best assess the risk of hyperhomocysteinemia, coronary heart disease (CHD), and diabetes mellitus. In this cross-sectional study, we studied 581 hypertensive Saudis, aged 21-70, at the King Abdul-Aziz University Hospital, from June 2005 to December 2005 Each participant completed the questionnaire and underwent a complete physical examination. Metabolic parameters were measured using routine laboratory procedures and homocysteine using HPLC by the electrochemical detection method. According to the International Diabetes Federation (IDF) definition we diagnosed 222 males and 256 females. There is an increased risk for hyperhomocystenemia using the Adult Treatment Panel III (ATPIII) guidelines (odds ratio [OR] 3.30, 95% confidence interval [CI] 0.87-12.56; p=0.08) compared to IDF (OR 0.59, CI 0.17-2.10; p=0.41) and WHO (OR 0.45, CI 0.16-1.25; p=0.12); increased risk for probable CHD in patients with MS by WHO (OR 2.17, CI 1.11-4.25; p=0.02) compared to ATPIII (OR 2.14, CI 1.05-4.35; p=0.035) and IDF (OR 0.81, CI 0.37-1.78; p=0.6); risk of DM is highest with IDF (OR 13.07, CI 1.66-102.94; p=0.015). There is a high prevalence of MS among hypertensive Saudis regardless of definition used; it is most prevalent using the IDF definition as well as the risk for diabetes Patients diagnosed with ATPIII guidelines have greater risk of hyperhomocysteinemia. We recommend the WHO definition for Arabs since it predicts increased risk for CHD. (author)

  14. Health Deficiencies

    Data.gov (United States)

    U.S. Department of Health & Human Services — A list of all health deficiencies currently listed on Nursing Home Compare, including the nursing home that received the deficiency, the associated inspection date,...

  15. Hepatic Effects of Pharmacological Doses of Hydroxy-Cobalamin[c-lactam] in Mice.

    Directory of Open Access Journals (Sweden)

    Patrizia Haegler

    Full Text Available The vitamin B12 analog hydroxy-cobalamin[c-lactam] (HCCL impairs hepatic mitochondrial protein synthesis and function of the electron transport chain in rats. We aimed to establish an in vivo model for mitochondrial dysfunction in mice, which could be used to investigate hepatotoxicity of mitochondrial toxicants. In a first step, we performed a dose-finding study in mice treated with HCCL 0.4 mg/kg and 4 mg/kg i.p. for two to four weeks. The plasma methylmalonate concentration was strongly increased at 4 mg/kg starting at three weeks of treatment. We subsequently treated mice daily with 4 mg/kg HCCL i.p. for three weeks and characterized liver function and histology as well as liver mitochondrial function. We found an increase in liver weight in HCCL-treated mice, which was paralleled by hepatocellular accumulation of triglycerides. In liver homogenate of HCCL-treated mice, the complex I activity of the electron transport chain was reduced, most likely explaining hepatocellular triglyceride accumulation. The activity of CPT1 was not affected by methylmalonyl-CoA in isolated liver mitochondria. Despite impaired complex I activity, mitochondrial superoxide anion production was not increased and the hepatocellular glutathione (GSH pool was maintained. Finally, the mitochondrial DNA content was not altered with HCCL treatment. In conclusion, treatment of mice with HCCL is associated with increased liver weight explained by hepatocellular triglyceride accumulation. Hepatocellular fat accumulation is most likely a consequence of impaired activity of the mitochondrial electron transport chain. The impairment of complex I activity is not strong enough to result in ROS accumulation and reduction of the GSH stores.

  16. [Neurological signs due to isolated vitamin B12 deficiency].

    Science.gov (United States)

    Martinez Estrada, K M; Cadabal Rodriguez, T; Miguens Blanco, I; García Méndez, L

    2013-01-01

    Isolated vitamin B12 deficiency is a common condition in elderly patients but uncommon in patients younger than 30 years, with an average age of onset between 60 and 70 years. This is because the dietary cobalamin, which is normally split by enzymes in meat in the presence of hydrochloric acid and pepsin in the stomach, is not released in the stomachs of elderly patients, usually due to achlorhydria. Although the body may be unable to release cobalamin it does retain the ability to absorb vitamin B12 in its crystalline form, which is present in multivitamin preparations. Other causes are due to drugs that suppress gastric acid production. Neurological signs of vitamin B12 deficiency can occur in patients with a normal haematocrit and red cell indices. They include paresthesia, loss of sensation and strength in the limbs, and ataxia. Reflexes may be slowed down or increased. Romberg and Babinsky signs may be positive, and vibration and position sensitivity often decreases. Behavoural disorders range from irritability and memory loss to severe dementia. The symptoms often do not fully respond to treatment. A case is presented of an isolated vitamin B12 deficiency in 27 year-old female patient who was seen in primary health care. During anamnesis she mentioned low back pain, to which she attributed the loss of strength and tenderness in the right side of the body, as well as the slow and progressive onset of accompanied headache for the previous 4 days. Copyright © 2012 Sociedad Española de Médicos de Atención Primaria (SEMERGEN). Publicado por Elsevier España. All rights reserved.

  17. Tratamento dietético da hiper-homocisteinemia na doença arterial periférica Dietary treatment of hyperhomocysteinemia in peripheral arterial disease

    Directory of Open Access Journals (Sweden)

    Luciene de Souza Venâncio

    2010-01-01

    Full Text Available A homocisteína está envolvida na gênese da aterosclerose e, assim, é considerada um importante e prevalente fator de risco na doença arterial periférica. O estado nutricional vitamínico deficiente, em especial do folato, é a principal causa de hiper-homocisteinemia nesses casos. Embora ainda não haja consenso sobre a dose exata e a forma de utilização do folato em suplementos e sobre adequação alimentar ou fortificação de cereais para o tratamento da hiper-homocisteinemia, diversos estudos realizados em pacientes com doença vascular periférica mostraram que o folato, isoladamente, pode reduzir as concentrações de homocisteína, bem como a concentração de alguns marcadores biológicos do processo de aterosclerose. No entanto, estudos recentes não comprovaram esse benefício sobre o processo inflamatório associado à hiper-homocisteinemia. Desta forma, embora a utilização isolada do folato seja uma terapêutica custo-efetiva no controle da hiper-homocisteinemia, seu impacto na evolução das doenças arteriais ainda persiste inconclusivo. Esta revisão abordará os efeitos obtidos com as diversas formas de utilização do folato no tratamento da hiper-homocisteinemia.Homocysteine plays a role in the genesis of atherosclerosis and, thus, it is considered an important and prevalent risk factor for peripheral arterial disease. Impaired vitamin nutritional status, especially regarding folate, may be mainly attributed to hyperhomocysteinemia. Although there is still no consensus as to the exact dose and method of use of folate in supplements, dietary adjustment or cereal fortification for the treatment of hyperhomocysteinemia, several studies conducted in patients with peripheral vascular disease have shown that isolated folate may reduce homocysteine levels, as well as the levels of some biological markers in the atherosclerotic process. However, recent studies have not corroborated this benefit for the inflammatory process

  18. [Hyperhomocysteinemia in coronary artery diseases. Apropos of a study on 102 patients].

    Science.gov (United States)

    Blacher, J; Montalescot, G; Ankri, A; Chadefaux-Vekemans, B; Benzidia, R; Grosgogeat, Y; Kamoun, P; Thomas, D

    1996-10-01

    Homocystein is at the crossroads of the metabolic pathways of sulphuric amino acids. Homocystinuria is a congenital autosomal recessive disease, usually related to cystathionine beta-synthetase deficiency. Children with homozygotic forms of the disease have early vascular complications which represent the main cause of death. Moderately elevated serum homocystein levels are related to two major genetic factors (heterozygotic cystathionine beta-synthetase deficiency and mutation of the 5-10 methylene tetrahydrofolate reductase) and several minor, genetic and non-genetic factors (folic acid, vitamins B6 and B12 and betain deficiencies). Previous studies have suggested that hyperhomocysteinaemia could be a cardiovascular risk factor. This study was based on 222 subjects including 102 consecutive patients with angiographically documented coronary artery disease and 120 control subjects without vascular disease. No relationship was observed between serum homocystein concentrations and the classical cardiovascular risk factors. Coronary patients had higher average homocystein concentrations than control subjects (11.27 +/- 0.52 vs 8.77 +/- 0.31 mumol/l); p 15.67 mumol/l) was higher in the coronary group (15.7%) than in the controls (2.5%). A significant relationship was also observed between homocystein concentrations and the severity of the coronary disease (defined by a coronary score) and the number of diseased vascular territories. These results underline the relationship between homocystein and vascular risk, especially that of coronary artery disease. The treatment of hyperhomocysteinaemia by folic acid supplements is effective in correcting plasma levels, without side effects and at a relatively low cost.

  19. The effect of the oxidation state of the folate standard on the results of the simultaneous radioassay of serum folate and cobalamin

    International Nuclear Information System (INIS)

    Lindemans, J.; Kapel, J. van

    1981-01-01

    The authors have compared a commercial radioisotope dilution assay using pteroylglutamic acid as a standard and a non-commercial assay using L-methyl-tetrahydrofolate as a standard. The iodinated tracer folate was the same in both methods. Both assays measure folate and colabamin simultaneously, which gave the opportunity to discuss also the results of the cobalamin assay. (Auth.)

  20. Oxidative stress inactivates cobalamin-independent methionine synthase (MetE in Escherichia coli.

    Directory of Open Access Journals (Sweden)

    Elise R Hondorp

    2004-11-01

    Full Text Available In nature, Escherichia coli are exposed to harsh and non-ideal growth environments-nutrients may be limiting, and cells are often challenged by oxidative stress. For E. coli cells confronting these realities, there appears to be a link between oxidative stress, methionine availability, and the enzyme that catalyzes the final step of methionine biosynthesis, cobalamin-independent methionine synthase (MetE. We found that E. coli cells subjected to transient oxidative stress during growth in minimal medium develop a methionine auxotrophy, which can be traced to an effect on MetE. Further experiments demonstrated that the purified enzyme is inactivated by oxidized glutathione (GSSG at a rate that correlates with protein oxidation. The unique site of oxidation was identified by selectively cleaving N-terminally to each reduced cysteine and analyzing the results by liquid chromatography mass spectrometry. Stoichiometric glutathionylation of MetE by GSSG occurs at cysteine 645, which is strategically located at the entrance to the active site. Direct evidence of MetE oxidation in vivo was obtained from thiol-trapping experiments in two different E. coli strains that contain highly oxidizing cytoplasmic environments. Moreover, MetE is completely oxidized in wild-type E. coli treated with the thiol-oxidizing agent diamide; reduced enzyme reappears just prior to the cells resuming normal growth. We argue that for E. coli experiencing oxidizing conditions in minimal medium, MetE is readily inactivated, resulting in cellular methionine limitation. Glutathionylation of the protein provides a strategy to modulate in vivo activity of the enzyme while protecting the active site from further damage, in an easily reversible manner. While glutathionylation of proteins is a fairly common mode of redox regulation in eukaryotes, very few proteins in E. coli are known to be modified in this manner. Our results are complementary to the independent findings of Leichert

  1. Helicobacter pylori Infection is a Significant Factor Risk for Hyperhomocysteinemia in the Patients with Coronary Artery Disease

    Directory of Open Access Journals (Sweden)

    Soudabeh Fallah

    2016-01-01

    Full Text Available ABSTRACT This work aimed to determine whether seropositivity to Helicobacter pylori infection was an independent risk factor for hyperhomocysteinemia patients with cardiovascular disease. The H. pylori IgG, IgA and homocystein levels in 96 patients with cardiovascular disease and 64 participants free of cardiovascular disease as control subjects were determined by ELISA assay. The results showed that seropositivity to H. pylori IgG and IgA levels of coronary artery disease (CADpatients was significantly higher than the controls and CAD patients with H. pylori IgG and IgA negative antibodies. A significant correlation was found between the seropositivity to H. pylori IgG and homocysteine levels of CAD patients in comparison with the controls and CAD patients with seronegativity to H. pylori IgG and IgA (r=0.233, P= 0.019 . The involvement of H. pylori infection in atherosclerosis process was based on the chronic inflammation, which might facilitate the CAD-related pathologies. The effect of the presence of H. pylori infection on homocysteine levels elevation in the CAD patients (as a risk factor independent of other traditional factors was remarkable.

  2. Creatine supplementation prevents hyperhomocysteinemia, oxidative stress and cancer-induced cachexia progression in Walker-256 tumor-bearing rats.

    Science.gov (United States)

    Deminice, Rafael; Cella, Paola Sanches; Padilha, Camila S; Borges, Fernando H; da Silva, Lilian Eslaine Costa Mendes; Campos-Ferraz, Patrícia L; Jordao, Alceu Afonso; Robinson, Jason Lorne; Bertolo, Robert F; Cecchini, Rubens; Guarnier, Flávia Alessandra

    2016-08-01

    The purpose of this study was to investigate (1) the impact of tumor growth on homocysteine (Hcy) metabolism, liver oxidative stress and cancer cachexia and, (2) the potential benefits of creatine supplementation in Walker-256 tumor-bearing rats. Three experiments were conducted. First, rats were killed on days 5 (D5), 10 (D10) and 14 (D14) after tumor implantation. In experiment 2, rats were randomly assigned to three groups designated as control (C), tumor-bearing (T) and tumor-bearing supplemented with creatine (TCr). A life span experiment was conducted as the third experiment. Creatine was supplied in drinking water for 21 days (8 g/L) in all cases. Tumor implantation consisted of a suspension of Walker-256 cells (8.0 × 10(7) cells in 0.5 mL of PBS). The progressive increase (P creatine supplementation promoted a 28 % reduction of tumor weight (P Creatine supplementation was unable to decrease Hcy concentration and to increase SAM/SAH ratio in tumor tissue. These data suggest that creatine effects on hepatic impaired Hcy metabolism promoted by tumor cell inoculation are responsible to decrease plasma Hcy in tumor-bearing rats. In conclusion, Walker-256 tumor growth is associated with progressive hyperhomocysteinemia, body weight loss and liver oxidative stress in rats. Creatine supplementation, however, prevented these tumor-associated perturbations.

  3. Iodine Deficiency

    NARCIS (Netherlands)

    Zimmermann, M.B.

    2009-01-01

    Iodine deficiency has multiple adverse effects in humans, termed iodine deficiency disorders, due to inadequate thyroid hormone production. Globally, it is estimated that 2 billion individuals have an insufficient iodine intake, and South Asia and sub-Saharan Africa are particularly affected.

  4. Hyperhomocysteinemia, methylenetetrahydrofolate reductase c.677C>T polymorphism and risk of cancer: cross-sectional and prospective studies and meta-analyses of 75,000 cases and 93,000 controls

    DEFF Research Database (Denmark)

    Zacho, Jeppe; Yazdanyar, Shiva; Bojesen, Stig E

    2011-01-01

    from 1.0. However, in meta-analyses odds ratio for MTHFR c.677C>T homozygotes versus noncarriers were 1.07 (95% CI: 1.01-1.12) for any cancer, 1.77 (1.17-2.68) for esophagus cancer, 1.40 (1.19-1.66) for gastric cancer and 0.85 (0.77-0.94) for colorectal cancer. Increased plasma homocysteine levels...... are not associated with an increased age-adjusted risk of any cancer. However, MTHFR c.677C>T homozygosity with lifelong hyperhomocysteinemia and hence hypomethylation associate with increased risk of esophagus and gastric cancer, and with decreased risk of colorectal cancer.......Global DNA hypomethylation associates with development of cancer. DNA hypomethylation also associates with hyperhomocysteinemia and MTHFR c.677C>T homozygosity, both of which may associate with increased risk of cancer. We tested the putative association of hyperhomocysteinemia with cancer...

  5. Trans and cis effects of axial fluoroalkyl ligands in vitamin B12 analogues: relationship between alkyl- and fluoroalkyl-cobalamins.

    Science.gov (United States)

    Randaccio, Lucio; Brancatelli, Giovanna; Demitri, Nicola; Dreos, Renata; Hickey, Neal; Siega, Patrizia; Geremia, Silvano

    2013-12-02

    CF2HCbl, CF3Cbl , and CF3CH2Cbl have been synthesized and characterized in solution by (1)H NMR and UV-vis spectroscopy, and their X-ray crystal structures have been determined using synchrotron radiation. The structure of CF3CH2Cbl is reported for the first time, whereas those of CF2HCbl and CF3Cbl are re-examined to obtain more precise structural data. Comparison of the structural data obtained with the alkylcobalamin analogues, MeCbl and EtCbl, indicates that the Co-C and Co-NB3 bond lengths are shorter in the fluoroalkylcobalamins. The structural data of the fluoroalkylcobalamins previously reported in the literature had been conflicting in this regard. Thus, a much less dramatic shortening of the two axial bonds was found for CF3Cbl, whereas in the case of CF2HCbl, the Co-NB3 bond length is shorter than in MeCbl. Direct comparison of the structures of CF3CH2Cbl and EtCbl indicates a large distortion of the axial fragment in the former case that can be attributed to steric effects. A number of previously reported correlations of the effect of the β-ligand on the structure and properties of cobalamins are re-examined in light of the present results. Particular emphasis is placed on the axial fragment. This analysis substantially confirms and, with the new data reported here, adjusts and expands the data set for correlations between trans and cis influences of the β-ligand of cobalamins and their structure (Co-X and Co-NB3 distances and corrin fold angle) and properties (UV-vis spectra, NMR spectra, and pK(base-off)).

  6. Electron addition to alkyl cobalamins, coenzyme B/sub 12/ and vitamin B/sub 12/. [Gamma radiation

    Energy Technology Data Exchange (ETDEWEB)

    Rao, D N.R.; Symons, M C.R. [Leicester Univ. (UK). Dept. of Chemistry

    1983-01-01

    Exposure of dilute solutions of methyl and ethyl cobalamins and coenzyme B/sub 12/ in dilute solutions (D/sub 2/O+CD/sub 3/OD) to /sup 60/Co ..gamma..-rays at 77 K gave a single broad feature in the free-spin region assigned to electron-capture species with the excess electron largely confined to a ..pi..* corrin orbital. On warming above 77 K the methyl derivative gave a novel species with spectral features characteristic of an unpaired electron in the Co(dsub(x/sup 2/-y/sup 2/)) orbital. The other two substrates gave spectra due to Cosup(II)Bsub(12r) both on warming and after photolyses with visible light. The acetyl derivative gave an electron-capture species whose e.s.r. spectrum was characteristic of an electron in the Co(dsub(z/sup 2/)) orbital, which on warming above 77 K changed to the normal Cosup(II)Bsub(12r) spectrum. The cyano derivative (vitamin B/sub 12/) gave electron addition into the Co(dsub(z/sup 2/)) orbital, as evidenced by the large hyperfine coupling to /sup 13/C from /sup 13/CN ligands. On annealing, cyanide ions were lost irreversibly, Bsub(12r) being detected by e.s.r. spectroscopy. In contrast, the dicyano derivative on electron addition at 77 K gave a species containing only one /sup 13/CN ligand. Hence in this case one CN/sup -/ ligand was lost at 77 K, with no return of the dimethylbenzimidazole ligand. These results are discussed in terms of a new mechanism for electron-addition to alkyl cobalamins.

  7. Cobalamin-Independent Methionine Synthase (MetE): A Face-to-Face Double Barrel that Evolved by Gene Duplication

    Energy Technology Data Exchange (ETDEWEB)

    Pejcha, Robert; Ludwig, Martha L. (Michigan)

    2010-03-08

    Cobalamin-independent methionine synthase (MetE) catalyzes the transfer of a methyl group from methyltetrahydrofolate to L-homocysteine (Hcy) without using an intermediate methyl carrier. Although MetE displays no detectable sequence homology with cobalamin-dependent methionine synthase (MetH), both enzymes require zinc for activation and binding of Hcy. Crystallographic analyses of MetE from T. maritima reveal an unusual dual-barrel structure in which the active site lies between the tops of the two ({beta}{alpha}){sub 8} barrels. The fold of the N-terminal barrel confirms that it has evolved from the C-terminal polypeptide by gene duplication; comparisons of the barrels provide an intriguing example of homologous domain evolution in which binding sites are obliterated. The C-terminal barrel incorporates the zinc ion that binds and activates Hcy. The zinc-binding site in MetE is distinguished from the (Cys){sub 3}Zn site in the related enzymes, MetH and betaine-homocysteine methyltransferase, by its position in the barrel and by the metal ligands, which are histidine, cysteine, glutamate, and cysteine in the resting form of MetE. Hcy associates at the face of the metal opposite glutamate, which moves away from the zinc in the binary E {center_dot} Hcy complex. The folate substrate is not intimately associated with the N-terminal barrel; instead, elements from both barrels contribute binding determinants in a binary complex in which the folate substrate is incorrectly oriented for methyl transfer. Atypical locations of the Hcy and folate sites in the C-terminal barrel presumably permit direct interaction of the substrates in a ternary complex. Structures of the binary substrate complexes imply that rearrangement of folate, perhaps accompanied by domain rearrangement, must occur before formation of a ternary complex that is competent for methyl transfer.

  8. Cobalamin-Independent Methionine Synthase (MetE): A Face-to-Face Double Barrel that Evolved by Gene Duplication

    International Nuclear Information System (INIS)

    Pejcha, Robert; Ludwig, Martha L.

    2005-01-01

    Cobalamin-independent methionine synthase (MetE) catalyzes the transfer of a methyl group from methyltetrahydrofolate to L-homocysteine (Hcy) without using an intermediate methyl carrier. Although MetE displays no detectable sequence homology with cobalamin-dependent methionine synthase (MetH), both enzymes require zinc for activation and binding of Hcy. Crystallographic analyses of MetE from T. maritima reveal an unusual dual-barrel structure in which the active site lies between the tops of the two (βα) 8 barrels. The fold of the N-terminal barrel confirms that it has evolved from the C-terminal polypeptide by gene duplication; comparisons of the barrels provide an intriguing example of homologous domain evolution in which binding sites are obliterated. The C-terminal barrel incorporates the zinc ion that binds and activates Hcy. The zinc-binding site in MetE is distinguished from the (Cys) 3 Zn site in the related enzymes, MetH and betaine-homocysteine methyltransferase, by its position in the barrel and by the metal ligands, which are histidine, cysteine, glutamate, and cysteine in the resting form of MetE. Hcy associates at the face of the metal opposite glutamate, which moves away from the zinc in the binary E · Hcy complex. The folate substrate is not intimately associated with the N-terminal barrel; instead, elements from both barrels contribute binding determinants in a binary complex in which the folate substrate is incorrectly oriented for methyl transfer. Atypical locations of the Hcy and folate sites in the C-terminal barrel presumably permit direct interaction of the substrates in a ternary complex. Structures of the binary substrate complexes imply that rearrangement of folate, perhaps accompanied by domain rearrangement, must occur before formation of a ternary complex that is competent for methyl transfer.

  9. Cobalamin-independent methionine synthase (MetE: a face-to-face double barrel that evolved by gene duplication.

    Directory of Open Access Journals (Sweden)

    Robert Pejchal

    2005-02-01

    Full Text Available Cobalamin-independent methionine synthase (MetE catalyzes the transfer of a methyl group from methyltetrahydrofolate to L-homocysteine (Hcy without using an intermediate methyl carrier. Although MetE displays no detectable sequence homology with cobalamin-dependent methionine synthase (MetH, both enzymes require zinc for activation and binding of Hcy. Crystallographic analyses of MetE from T. maritima reveal an unusual dual-barrel structure in which the active site lies between the tops of the two (betaalpha(8 barrels. The fold of the N-terminal barrel confirms that it has evolved from the C-terminal polypeptide by gene duplication; comparisons of the barrels provide an intriguing example of homologous domain evolution in which binding sites are obliterated. The C-terminal barrel incorporates the zinc ion that binds and activates Hcy. The zinc-binding site in MetE is distinguished from the (Cys(3Zn site in the related enzymes, MetH and betaine-homocysteine methyltransferase, by its position in the barrel and by the metal ligands, which are histidine, cysteine, glutamate, and cysteine in the resting form of MetE. Hcy associates at the face of the metal opposite glutamate, which moves away from the zinc in the binary E.Hcy complex. The folate substrate is not intimately associated with the N-terminal barrel; instead, elements from both barrels contribute binding determinants in a binary complex in which the folate substrate is incorrectly oriented for methyl transfer. Atypical locations of the Hcy and folate sites in the C-terminal barrel presumably permit direct interaction of the substrates in a ternary complex. Structures of the binary substrate complexes imply that rearrangement of folate, perhaps accompanied by domain rearrangement, must occur before formation of a ternary complex that is competent for methyl transfer.

  10. Association of Methylenetetrahydrofolate Reductase C677T Polymorphism with Hyperhomocysteinemia and Deep Vein Thrombosis in the Iranian Population.

    Science.gov (United States)

    Ghaznavi, Habib; Soheili, Zahra; Samiei, Shahram; Soltanpour, Mohammad Soleiman

    2015-12-01

    Deep venous thrombosis (DVT) is a common but elusive condition characterized by a high morbidity and mortality rate. The aim of the present study was to investigate the correlation between methylenetetrahydrofolate reductase (MTHFR) C677T polymorphism with plasma total homocysteine (tHcy) levels and DVT risk in an Iranian population. Our study population consisted of 67 patients with a diagnosis of DVT and 67 healthy subjects as controls. Genotyping of MTHFR C677T polymorphism was performed by the polymerase chain reaction technique combined with restriction enzyme fragment length polymorphism (PCR-RFLP) and measurement of tHcy levels was done by enzyme immunoassay method. Plasma tHcy levels were significantly higher in DVT patients than controls (18.09±7.6 vs. 10.5±4.3, P=0.001). Also, plasma tHcy levels were significantly higher in MTHFR 677TT genotypes compared to 677CC genotypes in both DVT patients (P=0.016) and controls (P=0.03). Neither heterozygote nor homozygote genotypes of MTHFR C677T polymorphism was significantly correlated with DVT (P>0.05). The distribution of MTHFR C677T genotypes was similar between men and women in both DVT patients and controls (P>0.05). Moreover, the frequency of mutant 677T allele did not differ significantly between the two groups (28.3% vs. 21.6%, P=0.15). Based on this study, we propose that hyperhomocysteinemia but not homozygosity for MTHFR C677T polymorphism is a significant risk factor for DVT in the Iranian population. Also, MTHFR 677TT genotype is a determinant of elevated plasma tHcy levels.

  11. The Effect of Hyperhomocysteinemia on Motor Symptoms, Cognitive Status, and Vascular Risk in Patients with Parkinson’s Disease

    Directory of Open Access Journals (Sweden)

    Bilge Kocer

    2016-01-01

    Full Text Available Factors related with hyperhomocysteinemia (HHcy and the impact of HHcy in Parkinson’s disease (PD are not well understood. We investigated the factors associated with increased levels of homocysteine (Hcy and the relationship between HHcy and motor symptoms, cognitive status, and vascular risk in patients with Parkinson’s disease. Among 60 patients (29 males, 48.3% with PD, the stage of the disease, the severity of clinical symptoms, and the patients’ cognitive status were measured using a modified Hoehn and Yahr Staging Scale (mHY, Unified Parkinson’s Disease Rating Scale (UPDRS II and III, and Mini-Mental State Examination (MMSE, respectively. Patients were also noted for having dyskinesia and hallucinations. Serum vitamin B12, folic acid, and plasma Hcy ​​levels were measured. Furthermore, the presence of vascular risk factors was recorded. Finally, we investigated carotid artery intima-media thickening and stenosis using colour Doppler ultrasonography as well as the presence of ischemic lesions using brain imaging techniques. Plasma Hcy ​​levels were higher with advanced age and in males. In addition, there was an inverse relationship between Hcy ​​and vitamin B12 levels. There was no correlation between HHcy and the stage of the disease, severity of motor symptoms, cognitive status as assessed by the MMSE, vascular risk factors, carotid artery atherosclerotic findings, and ischemic brain lesions. Plasma Hcy levels may rise due to several factors in PD. However, the resulting HHcy has no significant effect on the clinical picture in terms of motor features, cognitive status, and vascular diseases.

  12. Effect of taurine supplementation on hyperhomocysteinemia and markers of oxidative stress in high fructose diet induced insulin resistance

    Directory of Open Access Journals (Sweden)

    El Mesallamy Hala O

    2010-06-01

    Full Text Available Abstract Background High intake of dietary fructose is accused of being responsible for the development of the insulin resistance (IR syndrome. Concern has arisen because of the realization that fructose, at elevated concentrations, can promote metabolic changes that are potentially deleterious. Among these changes is IR which manifests as a decreased biological response to normal levels of plasma insulin. Methods Oral glucose tolerance tests (OGTT were carried out, homeostasis model assessment of insulin resistance (HOMA was calculated, homocysteine (Hcy, lipid concentrations and markers of oxidative stress were measured in male Wistar rats weighing 170-190 g. The rats were divided into four groups, kept on either control diet or high fructose diet (HFD, and simultaneously supplemented with 300 mg/kg/day taurine via intra-peritoneal (i.p. route for 35 days. Results Fructose-fed rats showed significantly impaired glucose tolerance, impaired insulin sensitivity, hypertriglyceridemia, hypercholesterolemia, hyperhomocysteinemia (HHcy, lower total antioxidant capacity (TAC, lower paraoxonase (PON activity, and higher nitric oxide metabolites (NOx concentration, when compared to rats fed on control diet. Supplementing the fructose-fed rats with taurine has ameliorated the rise in HOMA by 56%, triglycerides (TGs by 22.5%, total cholesterol (T-Chol by 11%, and low density lipoprotein cholesterol (LDL-C by 21.4%. Taurine also abolished any significant difference of TAC, PON activity and NOx concentration among treated and control groups. TAC positively correlated with PON in both rats fed on the HFD and those received taurine in addition to the HFD. Fructose-fed rats showed 34.7% increase in Hcy level. Taurine administration failed to prevent the observed HHcy in the current dosage and duration. Conclusion Our results indicate that HFD could induce IR which could further result in metabolic syndrome (MS, and that taurine has a protective role against

  13. Effects of isolated vitamin B6 supplementation on oxidative stress and heart function parameters in experimental hyperhomocysteinemia

    Directory of Open Access Journals (Sweden)

    Roberta Hack Mendes

    2017-07-01

    Full Text Available Introduction: The purpose of this study was to investigate the effects of isolated vitamin B6 (VB6 supplementation on experimental hyperhomocysteinemia (Hhe induced by homocysteine thiolactone (HcyT. Methods: Fifteen male Wistar rats were divided into three groups according to their treatment. Animals received water and food ad libitum and an intragastric probe was used to administer water for 60 days (groups: CB6, HcyT, and HB6. On the 30th day of treatment, two groups were supplemented with VB6 in the drinking water (groups: CB6 and HB6. After 60 days of treatment, homocysteine (Hcy, cysteine, and hydrogen peroxide concentration, nuclear factor (erythroid-derived 2-like 2 (NRF2 and glutathione S-transferase (GST immunocontent, and superoxide dismutase (SOD, catalase (CAT, and GST activities were measured. Results: The HcyT group showed an increase in Hcy concentration (62% in relation to the CB6 group. Additionally, GST immunocontent was enhanced (51% in the HB6 group compared to the HcyT group. Also, SOD activity was lower (17% in the HB6 group compared to the CB6 group, and CAT activity was higher in the HcyT group (53% compared to the CB6 group. Ejection fraction (EF was improved in the HB6 group compared to the HcyT group. E/A ratio was enhanced in the HB6 group compared to the CB6 group. Correlations were found between CAT activity with myocardial performance index (MPI (r = 0.71; P = 0.06 and E/A ratio (r = 0.6; P = 0.01, and between EF and GST activity (r = 0.62; P = 0.02. Conclusions: These findings indicate that isolated VB6 supplementation may lead to the reduction of Hcy concentration and promotes additional benefits to oxidative stress and heart function parameters.   Keywords: Homocysteine; oxidative stress; vitamin B6.

  14. Is vitamin B12 deficiency a risk factor for cardiovascular disease in vegetarians?

    Science.gov (United States)

    Pawlak, Roman

    2015-06-01

    The goal of this paper is to describe the role of vitamin B12 deficiency in cardiovascular disease development among vegetarians. Vegetarians have a high prevalence of vitamin B12 deficiency. Deficiency of this vitamin is associated with a variety of atherogenic processes that are mainly, but not exclusively, due to vitamin B12 deficiency-induced hyperhomocysteinemia. Each 5-μmol/L increase above 10 μmol/L of serum homocysteine is associated with a 20% increased risk of circulatory health problems. Mean homocysteine concentration >10 μmol/L among vegetarians was reported in 32 of 34 reports. Macrocytosis associated with vitamin B12 deficiency is also associated with fatal and non-fatal coronary disease, myocardial infarction, stroke, and other circulatory health problems. Compared with non-vegetarians, vegetarians have an improved profile of the traditional cardiovascular disease risk factors, including serum lipids, blood pressure, serum glucose concentration, and weight status. However, not all studies that assessed cardiovascular disease incidence among vegetarians reported a protective effect. Among studies that did show a lower prevalence of circulatory health problems, the effect was not as pronounced as expected, which may be a result of poor vitamin B12 status due to a vegetarian diet. Vitamin B12 deficiency may negate the cardiovascular disease prevention benefits of vegetarian diets. In order to further reduce the risk of cardiovascular disease, vegetarians should be advised to use vitamin B12 supplements. Copyright © 2015 American Journal of Preventive Medicine. Published by Elsevier Inc. All rights reserved.

  15. Hyperhomocysteinemia is an independent predictor of long-term clinical outcomes in Chinese octogenarians with acute coronary syndrome

    Directory of Open Access Journals (Sweden)

    Fu Z

    2015-09-01

    curve analysis indicated the predictive cutoff value of Hcy for all-cause mortality was 17.67 µmol/L (0.667, 0.681.Conclusion: In ACS octogenarians, hyperhomocysteinemia is an important predictor for long-term all-cause mortality and MACE. Keywords: acute coronary syndrome, octogenarian, homocysteine, clinical risk factors, outcomes

  16. Cobalt-deficiency-induced hyperhomocysteinaemia and oxidative status of cattle.

    Science.gov (United States)

    Stangl, G I; Schwarz, F J; Jahn, B; Kirchgessner, M

    2000-01-01

    In ruminants, Co is required for the synthesis of vitamin B12, which in turn is needed for the resynthesis of methionine by methylation of homocysteine and thus, cobalamin deficiency may induce hyperhomocysteinaemia which is brought into context with perturbations of the antioxidative-prooxidative balance. The present study was conducted to explore whether Co deficiency in cattle is also associated with homocysteine-induced disturbances of oxidative status. Co deficiency was induced in cattle by feeding two groups of animals on either a basal maize-silage-based diet that was moderately low in Co (83 micrograms Co/kg DM), or the same diet supplemented with Co to a total of 200 micrograms Co/kg DM, for 43 weeks. Co deficiency was apparent from a reduced vitamin B12 status in serum and liver and an accumulation of homocysteine in plasma which was in excess of 4.8 times higher in Co-deprived cattle than in controls. The much increased level of circulating homocysteine did not indicate severe disturbances in antioxidant-prooxidant balance as measured by individual markers of lipid peroxidation, protein oxidation, and the antioxidative defence system. There were no quantitative difference in plasma thiol groups, nor were there significant changes in concentrations of alpha-tocopherol, microsomal thiobarbituric acid-reactive substances and carbonyl groups in liver. However, there was a trend toward increased plasma carbonyl levels indicating a slight degradation of plasma proteins in the hyperhomocysteinaemic cattle. Analysis of the hepatic catalase (EC 1.11.1.6) activity revealed an 11% reduction in Co-deficient cattle relative to the controls. These results indicate that long-term moderate Co deficiency may induce a severe accumulation of plasma homocysteine in cattle, but considerable abnormalities in oxidative status failed to appear.

  17. What Are Rare Clotting Factor Deficiencies?

    Science.gov (United States)

    ... Deficiency Factor V Deficiency Combined FV & FVIII Deficiencies Factor VII Deficiency Factor X Deficiency Factor XI Deficiency Factor ... Deficiency Factor V Deficiency Combined FV & FVIII Deficiencies Factor VII Deficiency Factor X Deficiency Factor XI Deficiency Factor ...

  18. Cobalamin speciation using reversed-phase micro-high-performance liquid chromatography interfaced to inductively coupled plasma mass spectrometry

    International Nuclear Information System (INIS)

    Yanes, Enrique G.; Miller-Ihli, Nancy J.

    2004-01-01

    Micro-high-performance liquid chromatography interfaced to inductively coupled plasma mass spectrometry was optimized for the determination and separation of a mixture of cobalt containing species. Four cobalamin species (cyanocobalamin, hydroxocobalamin, methylcobalamin, and 5'-deoxyadenosylcobalamin) representing the various forms of vitamin B12 as well as the harmful corrinoid analogue cobinamide dicyanide were separated using reversed-phase microcapillary chromatography with columns containing C18 packing material with a 2-μm particle size. Selection of organic solvents for the separation took into consideration compatibility with the inductively coupled plasma mass spectrometer being used for element specific detection. Optimized method conditions included use of a methanol gradient and make-up solution for the nebulizer. Some issues associated with dead volume were overcome by the extension of the gradient program. The total analysis time was 52 min. The column-to-column variability was evaluated and was found to be very reasonable (9% RSD on average), confirming that this method is rugged and that the technology should be easily transferred to other laboratories

  19. Hyperhomocysteinemia in patients with chronic kidney disease and its relationship with the functional status of the cardiovascular system

    Directory of Open Access Journals (Sweden)

    K. P. Postovitenko

    2017-04-01

    Full Text Available Chronic kidney disease (CKD is an important medical, social and economic problem nowadays. Patients with CKD are known to have an increased risk of development and progression of cardiovascular diseases. However, the causes and pathogenesis of cardiovascular complications are not well understood. One of the recently recognized “non-traditional” risk factors for the increased development of cardiovascular pathology in severe stages of CKD is hyperhomocysteinemia (HHC. The article presents the results of study of HHC frequency in patients with different stages of CKD as well as the relationship between HHC and endothelial dysfunction and structural-functional status of the heart. The study involved 148 persons with different stages of CKD who underwent immunoenzyme determination of total plasma homocysteine (HC, echocardiography, carotid ultrasonograghy, endothelial function was assessed as well. It was found that among the patients with CKD, 26 (21.1% had normal and 34 (27.7% had subnormal HC levels, mild HHC was observed in 30 (24.4% and moderate HHC – in 33 (26.8% cases, i.e. the total number of patients with elevated HC level was 88.9%. It should be noted that no patients with normal HC level were found among those with stage four CKD as well as in dialysis patients. The increase of blood plasma HC level was actually proportional to the severity of renal failure, which in its turn led to the shift in the number of cases towards higher rank indices of HHC level. In particular, while there were no patients with HHC among those with CKD-I, more than 50% of such patients were found in the group with CKD-V. Reduced myocardial contractility and echocardiographic markers of left ventricular hypertrophy in patients with CKD were found to be closely associated with HC concentrations in blood plasma. The data presented clearly demonstrate strong inverse correlation between endothelial dysfunction indices and HC level. So, the endothelium

  20. Iron-Deficiency Anemia

    Medline Plus

    Full Text Available ... Research Home / < Back To Health Topics / Iron-Deficiency Anemia Iron-Deficiency Anemia Also known as Leer en español Iron-deficiency ... iron-deficiency anemia. Blood tests to screen for iron-deficiency anemia To screen for iron-deficiency anemia, your doctor ...

  1. Iron deficiency

    DEFF Research Database (Denmark)

    Schou, Morten; Bosselmann, Helle; Gaborit, Freja

    2015-01-01

    BACKGROUND: Both iron deficiency (ID) and cardiovascular biomarkers are associated with a poor outcome in heart failure (HF). The relationship between different cardiovascular biomarkers and ID is unknown, and the true prevalence of ID in an outpatient HF clinic is probably overlooked. OBJECTIVES.......043). CONCLUSION: ID is frequent in an outpatient HF clinic. ID is not associated with cardiovascular biomarkers after adjustment for traditional confounders. Inflammation, but not neurohormonal activation is associated with ID in systolic HF. Further studies are needed to understand iron metabolism in elderly HF...

  2. A Frameshift Mutation in the Cubilin Gene (CUBN) in Border Collies with Imerslund-Gräsbeck Syndrome (Selective Cobalamin Malabsorption)

    Science.gov (United States)

    Owczarek-Lipska, Marta; Jagannathan, Vidhya; Drögemüller, Cord; Lutz, Sabina; Glanemann, Barbara

    2013-01-01

    Imerslund-Gräsbeck syndrome (IGS) or selective cobalamin malabsorption has been described in humans and dogs. IGS occurs in Border Collies and is inherited as a monogenic autosomal recessive trait in this breed. Using 7 IGS cases and 7 non-affected controls we mapped the causative mutation by genome-wide association and homozygosity mapping to a 3.53 Mb interval on chromosome 2. We re-sequenced the genome of one affected dog at ∼10× coverage and detected 17 non-synonymous variants in the critical interval. Two of these non-synonymous variants were in the cubilin gene (CUBN), which is known to play an essential role in cobalamin uptake from the ileum. We tested these two CUBN variants for association with IGS in larger cohorts of dogs and found that only one of them was perfectly associated with the phenotype. This variant, a single base pair deletion (c.8392delC), is predicted to cause a frameshift and premature stop codon in the CUBN gene. The resulting mutant open reading frame is 821 codons shorter than the wildtype open reading frame (p.Q2798Rfs*3). Interestingly, we observed an additional nonsense mutation in the MRC1 gene encoding the mannose receptor, C type 1, which was in perfect linkage disequilibrium with the CUBN frameshift mutation. Based on our genetic data and the known role of CUBN for cobalamin uptake we conclude that the identified CUBN frameshift mutation is most likely causative for IGS in Border Collies. PMID:23613799

  3. B12 deficiency increases with age in hospitalized patients: a study on 14,904 samples.

    Science.gov (United States)

    Mézière, Anthony; Audureau, Etienne; Vairelles, Stéphane; Krypciak, Sébastien; Dicko, Michèle; Monié, Marguerite; Giraudier, Stéphane

    2014-12-01

    Cobalamin deficiency is responsible for hematological, neurological, neurocognitive, and neuropsychiatric impairments and is a risk factor for cardiovascular diseases, particularly in the elderly people. In order to determine B12 status in old inpatients, a total number of 14,904 hospitalized patients in whom B12 measurements were performed in five hospitals in the Paris metropolitan area were included from January 1, 2011 to December 31, 2011. The aims of the study were to determine whether age had an impact on B12 and folate deficiencies and to evaluate correlations between B12 and biological parameters-folate, hemoglobin, mean cell volume, homocystein (tHcy)-and age. Patients were aged 70.3±19.5 years. Low B12 concentration ( 17 µmol/L), 20.4% had low folate concentration (folate 17 µmol/L), and 4.7% of patients were both functional B12 and folate deficient. The B12 or folate deficient patients had lower mean cell volume level than nondeficient patients. Increase in mean cell volume and tHcy concentrations with age and decrease in B12, folate, and hemoglobin levels with age were observed. Frequency of functional B12 deficiency was 9.6% in patients aged 30-60 years and 14.2% in patients over 90 years. Frequency of functional folate deficiency was 9.5% in 30-60 years and 12.1% in >90 years. In inpatients, functional B12 deficiency and functional folate deficiency increase with age and are not associated with anemia or macrocytosis. False vitamin B deficiencies are frequent. © The Author 2014. Published by Oxford University Press on behalf of The Gerontological Society of America. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.

  4. Cobalamin (Vitamin B12) Role on the Biochemical, Histological and Teratological Changes Induced in Diabetic Irradiated Pregnant Rats

    International Nuclear Information System (INIS)

    Ramadan, F.L.

    2013-01-01

    Vitamin B 12 called Cobalamin, is a water soluble vitamin with a key role in the normal function of the brain, nervous system, cell division and for the formation of blood. It is normally involved in the metabolism of every cell of the human body especially affecting DNA synthesis and regulation, fatty acid synthesis and energy production.The aim of the present study was to evaluate the role of vitamin B 12 intake on radiation induced damage in diabetic mothers.Diabetes was induced in female rats by intra-peritoneal injection of alloxan 150 mg/kg b.wt. dissolved in saline. Pregnant diabetic mothers were received vitamin B 12 0.1 mg/100 g b.wt. from the 1st up to 19th day of gestation. Meanwhile, pregnant diabetic rats were exposed to 0.6 Gy on the 7th and the 14th days of gestation. The increased incidence of malformations in diabetic pregnancy with an excess of free oxygen radicals in the embryos was recorded .Vitamin B12 supplementation to diabetic mother ameliorated radiation-induced damage which was obvious by diminishing the increase in glucose level, improving serum insulin level, glycogen content in the liver and ameliorating the decrease in glutathione (GSH) content in the liver of pregnant rats and their fetuses.In addition, vitamin B 12 treatment improved the decrease in red blood cells (RBCs), white blood cells (WBCs) and hemoglobin (Hb) of fetuses and DNA content in the liver tissues. Moreover, vitamin B 12 treatment lead to the regeneration of normal architecture of maternal and fetuses hepatic cells and blood vessels. It could be concluded that vitamin B 12 supplementation to diabetic mothers ameliorated the radiation effect which induced biochemical, histochemical, histological and teratological disorders.Furthermore, the results obtained showed that vitamin B 12 administration caused a protection to diabetic pregnant rats against embryo malformations induced by gamma rays

  5. Iron-Deficiency Anemia

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    Full Text Available ... To Health Topics / Iron-Deficiency Anemia Iron-Deficiency Anemia Also known as Leer en español Iron-deficiency ... anemia. Blood tests to screen for iron-deficiency anemia To screen for iron-deficiency anemia, your doctor ...

  6. Iron-Deficiency Anemia

    Science.gov (United States)

    ... To Health Topics / Iron-Deficiency Anemia Iron-Deficiency Anemia Also known as Leer en español Iron-deficiency ... anemia. Blood tests to screen for iron-deficiency anemia To screen for iron-deficiency anemia, your doctor ...

  7. Iron-Deficiency Anemia

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    Full Text Available ... you are diagnosed with iron-deficiency anemia. Risk Factors You may have an increased risk for iron- ... iron-deficiency anemia if you have certain risk factors , including pregnancy. To prevent iron-deficiency anemia, your ...

  8. Iron-Deficiency Anemia

    Medline Plus

    Full Text Available ... to moderate iron-deficiency anemia, or red blood cell transfusion for severe iron-deficiency anemia. You may ... body needs iron to make healthy red blood cells. Iron-deficiency anemia usually develops over time because ...

  9. Vitamin Deficiency Anemia

    Science.gov (United States)

    ... are unique to specific vitamin deficiencies. Folate-deficiency anemia risk factors include: Undergoing hemodialysis for kidney failure. ... the metabolism of folate. Vitamin B-12 deficiency anemia risk factors include: Lack of intrinsic factor. Most ...

  10. Vitamin B12 Deficiency Presenting as Pancytopenia in Pregnancy: A Case Report

    Directory of Open Access Journals (Sweden)

    Idris N

    2012-12-01

    Full Text Available Vitamin B12 deficiency is a well-known cause of megaloblastic anaemia and pancytopenia. However, the incidence in pregnancy is rarely reported. We present a case of a 32-year old multigravid woman who was diagnosed with megaloblastic anaemia since 22 weeks gestation and progressed to develop severe pancytopenia at 30 weeks gestation. she was also diagnosed with vitamin B12 deficiency related to dietary and sociocultural habits. Folate and iron levels were normal throughout pregnancy. treatment with parenteral cyano-cobalamin resulted in sustained improvement of haematological parameters. the pregnancy was carried to term and the baby was born weighing 2,050gm but otherwise well at birth and had normal developmental milestones thereafter. this case illustrates the clinical presentation of maternal vitamin B12 deficiency and demonstrates the importance of detecting and treating maternal vitamin B12 deficiency during pregnancy in at-risk patients. Failure to diagnose and institute treatment carries significant risks to both mother and child. oral vitamin B12 supplementation should be considered for patients who are strict vegetarians or consume very little animal products.

  11. Synergistic effect of nano-sized mackinawite with cyano-cobalamin in cement slurries for reductive dechlorination of tetrachloroethylene

    Energy Technology Data Exchange (ETDEWEB)

    Kyung, Daeseung [Department of Civil and Environmental Engineering, Korea Advanced Institute of Science and Technology (KAIST), 291 Daehak-ro, Yuseong-gu, Daejeon 34141 (Korea, Republic of); Sihn, Youngho [Department of Nuclear and Quantum Engineering, Korea Advanced Institute of Science and Technology (KAIST), 291 Daehak-ro, Yuseong-gu, Daejeon 34141 (Korea, Republic of); Kim, Sangwoo [Department of Civil and Environmental Engineering, Korea Advanced Institute of Science and Technology (KAIST), 291 Daehak-ro, Yuseong-gu, Daejeon 34141 (Korea, Republic of); Bae, Sungjun [Department of Environmental Engineering, Konkuk University, 120 Neungdong-ro, Gwangjin-gu, Seoul 05029 (Korea, Republic of); Amin, Muhammad Tahir; Alazba, Abdulrahman Ali [Alamoudi Water Chair, King Saud University, Riyadh 11451 (Saudi Arabia); Lee, Woojin, E-mail: woojin_lee@kaist.ac.kr [Department of Civil and Environmental Engineering, Korea Advanced Institute of Science and Technology (KAIST), 291 Daehak-ro, Yuseong-gu, Daejeon 34141 (Korea, Republic of)

    2016-07-05

    Highlights: • Complete degradation of PCE was observed in nFeS-Cbl(III)-cement at pH 12. • PCE was completely degraded to non-chlorinated organic compounds by this system. • Co redox couple and Ca species in cement played a pivotal role for PCE reduction. • Increases in Cbl(III) concentration, cement ratio, and pH enhanced PCE degradation. • Efficiency of the system for PCE reduction was good even at high concentration of PCE. - Abstract: Experiments were conducted to investigate the reductive dechlorination of tetrachloroethylene (PCE) by nano-Mackinawite (nFeS) with cyano-cobalamin (Cbl(III)) in cement slurries. Almost complete degradation of PCE by nFeS-Cbl(III) was observed in cement slurries in 5 h and its degradation kinetics (k{sub obs-PCE} = 0.57 h{sup −1}) was 6-times faster than that of nFeS-Cbl(III) without the cement slurries. PCE was finally transformed to non-chlorinated organic compounds such as ethylene, acetylene, and C3-C4 hydrocarbons by nFeS-Cbl(III) in cement slurries. X-ray photoelectron spectroscopy and PCE degradation by cement components (SiO{sub 2}, Al{sub 2}O{sub 3}, and CaO) revealed that both the reduced Co species in Cbl(III) and the presence of Ca in cement played an important role for the enhanced reductive dechlorination of PCE. The increase in the concentration of Cbl(III) (0.005–0.1 mM), cement ratio (0.05–0.2), and suspension pH (11.5–13.5) accelerated the PCE degradation kinetics by providing more favorable environments for the production of reactive Ca species and reduction of Co species. We also observed that the degradation efficiency of PCE by nFeS-Cbl(III)-cement lasted even at high concentration of PCE. The experimental results obtained from this study could provide fundamental knowledge of redox interactions among nFeS, Cbl(III), and cement, which could significantly enhance reductive dechlorination of chlorinated organics in contaminated natural and engineered environments.

  12. Synergistic effect of nano-sized mackinawite with cyano-cobalamin in cement slurries for reductive dechlorination of tetrachloroethylene

    International Nuclear Information System (INIS)

    Kyung, Daeseung; Sihn, Youngho; Kim, Sangwoo; Bae, Sungjun; Amin, Muhammad Tahir; Alazba, Abdulrahman Ali; Lee, Woojin

    2016-01-01

    Highlights: • Complete degradation of PCE was observed in nFeS-Cbl(III)-cement at pH 12. • PCE was completely degraded to non-chlorinated organic compounds by this system. • Co redox couple and Ca species in cement played a pivotal role for PCE reduction. • Increases in Cbl(III) concentration, cement ratio, and pH enhanced PCE degradation. • Efficiency of the system for PCE reduction was good even at high concentration of PCE. - Abstract: Experiments were conducted to investigate the reductive dechlorination of tetrachloroethylene (PCE) by nano-Mackinawite (nFeS) with cyano-cobalamin (Cbl(III)) in cement slurries. Almost complete degradation of PCE by nFeS-Cbl(III) was observed in cement slurries in 5 h and its degradation kinetics (k_o_b_s_-_P_C_E = 0.57 h"−"1) was 6-times faster than that of nFeS-Cbl(III) without the cement slurries. PCE was finally transformed to non-chlorinated organic compounds such as ethylene, acetylene, and C3-C4 hydrocarbons by nFeS-Cbl(III) in cement slurries. X-ray photoelectron spectroscopy and PCE degradation by cement components (SiO_2, Al_2O_3, and CaO) revealed that both the reduced Co species in Cbl(III) and the presence of Ca in cement played an important role for the enhanced reductive dechlorination of PCE. The increase in the concentration of Cbl(III) (0.005–0.1 mM), cement ratio (0.05–0.2), and suspension pH (11.5–13.5) accelerated the PCE degradation kinetics by providing more favorable environments for the production of reactive Ca species and reduction of Co species. We also observed that the degradation efficiency of PCE by nFeS-Cbl(III)-cement lasted even at high concentration of PCE. The experimental results obtained from this study could provide fundamental knowledge of redox interactions among nFeS, Cbl(III), and cement, which could significantly enhance reductive dechlorination of chlorinated organics in contaminated natural and engineered environments.

  13. High fat diet-induced non alcoholic fatty liver disease in rats is associated with hyperhomocysteinemia caused by down regulation of the transsulphuration pathway

    Directory of Open Access Journals (Sweden)

    Napolitano Mariarosaria

    2011-04-01

    Full Text Available Abstract Background Hyperhomocysteinemia (HHcy causes increased oxidative stress and is an independent risk factor for cardiovascular disease. Oxidative stress is now believed to be a major contributory factor in the development of non alcoholic fatty liver disease, the most common liver disorder worldwide. In this study, the changes which occur in homocysteine (Hcy metabolism in high fat-diet induced non alcoholic fatty liver disease (NAFLD in rats were investigated. Methods and results After feeding rats a standard low fat diet (control or a high fat diet (57% metabolisable energy as fat for 18 weeks, the concentration of homocysteine in the plasma was significantly raised while that of cysteine was lowered in the high fat as compared to the control diet fed animals. The hepatic activities of cystathionine β-synthase (CBS and cystathionine γ-lyase (CGS, the enzymes responsible for the breakdown of homocysteine to cysteine via the transsulphuration pathway in the liver, were also significantly reduced in the high fat-fed group. Conclusions These results indicate that high fat diet-induced NAFLD in rats is associated with increased plasma Hcy levels caused by down-regulation of hepatic CBS and CGL activity. Thus, HHcy occurs at an early stage in high fat diet-induced NAFLD and is likely to contribute to the increased risk of cardiovascular disease associated with the condition.

  14. Iron-Deficiency Anemia

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    Full Text Available ... Iron-Deficiency Anemia Iron-Deficiency Anemia Also known as Leer en español Iron-deficiency anemia is a ... address the cause of your iron deficiency, such as any underlying bleeding. If undiagnosed or untreated, iron- ...

  15. Relationship between cobalamin-dependent metabolites and both serum albumin and alpha1 -proteinase inhibitor concentrations in hypocobalaminemic dogs of 7 different breeds.

    Science.gov (United States)

    Grützner, Niels; Suchodolski, Jan S; Steiner, Jörg M

    2014-12-01

    Increased serum concentrations of homocysteine (HCY) and methylmalonic acid (MMA), the 2 main cobalamin-dependent metabolites, as well as decreased serum albumin and canine alpha1 -proteinase inhibitor (cα1 -PI) concentrations have previously been described in hypocobalaminemic dogs with gastrointestinal disease. However, no studies have been conducted to evaluate potential relationships between these serum biomarkers. The aim of this study was to evaluate the relationship between HCY and MMA, 2 cobalamin-dependent metabolites, and both serum albumin and cα1 -PI concentrations in hypocobalaminemic dogs. Serum samples from 285 dogs including 7 different breeds (Beagle, Boxer, Cocker Spaniel, German Shepherd, Labrador Retriever, Chinese Shar-Pei, and Yorkshire Terrier) with hypocobalaminemia were used. Serum HCY, MMA, albumin, and cα1 -PI concentrations were determined. There was a significant correlation between serum HCY and albumin concentrations, as well as serum HCY and cα1 -PI concentrations (ρ = 0.62 and ρ = 0.37, respectively; P  .05). In addition, significant breed-specific correlations were observed between serum MMA and albumin concentrations in German Shepherds, and serum HCY and MMA concentrations in Chinese Shar-Peis with hypocobalaminemia. This study shows a correlation between serum albumin and cα1 -PI and HCY concentrations, but not with serum MMA concentration in dogs with hypocobalaminemia. In addition, significant breed-specific correlations were observed between serum MMA and albumin concentrations in German Shepherds, as well as serum HCY and MMA concentrations in Chinese Shar-Peis, emphasizing the unique metabolic interactions in those dog breeds affected by hypocobalaminemia. © 2014 American Society for Veterinary Clinical Pathology.

  16. Is Cholesterol Sulfate Deficiency a Common Factor in Preeclampsia, Autism, and Pernicious Anemia?

    Directory of Open Access Journals (Sweden)

    Jingjing Liu

    2012-11-01

    Full Text Available In a recent paper, we proposed that a contributing factor in autism is a deficiency in cholesterol sulfate supply. In this paper, we investigate a link between preeclampsia and subsequent autism in the child, and we hypothesize that both conditions can be attributed to a severe depletion of cholesterol sulfate. Through studies on the Vaccine Adverse Event Reporting System (VAERS database, we demonstrate a strong statistical relationship among the signs and symptoms associated with autism and those associated with preeclampsia, pernicious anemia, and serious adverse reactions to vaccines. We show that VAERS reports associated with symptoms typical of pernicious anemia produce both a set of symptoms that are highly correlated with preeclampsia and another set highly correlated with autism. We explain this observation via an argument that, in a severe reaction, the cascade of events subsequent to vaccination reflects a profuse production of nitric oxide (NO and consequential destruction of both red blood cells (RBCs and cobalamin. This may explain the diverse signs and symptoms associated with both preeclampsia and severe vaccine adverse reactions. We argue that excess NO synthesis, induced by the aluminum and antigen in vaccines, results in hemolysis of RBCs, which allows hemoglobin to scavenge the excess NO, converting it to nitrate. The NO is also scavenged by cobalamin, leading to its inactivation and contributing to subsequent pernicious anemia. Finally, we demonstrate that severe adverse reactions to vaccines can be associated with life-threatening conditions related to the heart and brain, as well as stillbirth, when the vaccine is administered to a woman in the third-trimester of pregnancy, as demonstrated by statistical analysis of the Gardasil records.

  17. Effects of donepezil combined with folic acid and vitamin B12 on serum levels of inflammatory factors, HCY, NSE and neurotransmitters in elderly patients with Alzheimer' s disease complicated with hyperhomocysteinemia

    Directory of Open Access Journals (Sweden)

    Fang-Fang Zheng

    2017-08-01

    Full Text Available Objective: To investigate the effects of donepezil combined with folic acid and vitamin B12 on the levels of serum inflammatory factors, Hcy, NSE and neurotransmitters in elderly patients with Alzheimer's disease (AD complicated with hyperhomocysteinemia. Methods: A total of 98 elderly patients with AD complicated with hyperhomocysteinemia were randomly divided into control group (n=48 and observation group (n=50 according to the random data table method. Patients in the control group were treated with donepezil. On this basis, the patients in the observation group were treated with folic acid and vitamin B12, all patients were treated for 3 months. Before and after treatment, the levels of serum inflammatory factors (TNF-α, IL-6 and hs-CRP, Hcy, NSE and brain neurotransmitter (5-HT, NE and DA were compared between the two groups. Results: Before treatment, the levels of TNF-α, IL-6, hs-CRP, Hcy, NSE, 5-HT, NE and DA of the control group and the observation group were not statistically significant. Compared with the group before treatment, the levels of TNF-α, IL-6, hs-CRP, Hcy and NSE in the two groups were significantly lower, and the level of the observation group was significantly lower than those of the control group, the difference was statistically significant; Compared with the group before treatment, the levels of 5-HT, NE and DA in the two groups were significantly increased, and the observation group was significantly higher than that of the control group, the difference was statistically significant. Conclusion: Donepezil combined folic acid and vitamin B12 in treatment of AD with hyperhomocysteinemia, which can effectively reduce the body's inflammatory response, reduced Hcy and NSE levels, elevated levels of brain neurotransmitters, has important clinical significance.

  18. Hiper-homocisteinemia e síndrome antifosfolípide primária Hyperhomocysteinemia and primary antiphospholipid syndrome

    Directory of Open Access Journals (Sweden)

    Jozélio Freire de Carvalho

    2009-08-01

    Full Text Available OBJETIVOS: Investigar a prevalência de hiper-homocisteinemia e suas possíveis associações clínicas e laboratoriais em pacientes com síndrome antifosfolípide primária (SAFP. PACIENTES E MÉTODOS: Estudo transversal de 27 pacientes (88% mulheres com SAFP (critérios de Sapporo. Foram avaliados dados demográficos, clínicos, comorbidades, medicações, anticorpos antifosfolípides, colhendo-se uma amostra de sangue para dosagem da homocisteína, pela técnica de cromatografia líquida de alta resolução. RESULTADOS: Seis (22% dos 27 pacientes apresentaram níveis de homocisteinemia acima dos valores normais (98,7 ± 8,9 versus 8,0 ± 2,9 ¼M, P = 0,0008. Comparando-se o grupo de pacientes com hiper-homocisteinemia com aquele que apresentava níveis normais, verificou-se que ambos os grupos de pacientes com SAFP não diferiram estatisticamente em relação aos dados demográficos (idade, cor branca, peso, altura e índice de massa corporal, bem como ao tempo de duração de doença (64 ± 39,6 versus 77,9 ± 61,3 meses, P = 0,32. Nenhum dos grupos apresentou diferenças quanto às manifestações da doença (eventos arteriais, venosos e obstétricos, trombose venosa profunda, tromboembolismo pulmonar, plaquetopenia, infarto agudo do miocárdio, angina e acidente vascular cerebral, comorbidades (hipertensão arterial e dislipidemia, ao estilo de vida (atividade física e tabagismos atual e pregresso, bem como ao uso de medicações (corticoide atual e pregresso, estatina, cloroquina e ácido acetilsalicílico. A prevalência e os títulos de anticorpos anticardiolipina foram semelhantes em ambos os grupos. CONCLUSÃO: A hiper-homocisteinemia pode ser detectada em cerca de um quarto da população com SAFP, sem associação com características distintivas clínicas e laboratoriais dessa doença.OBJECTIVES: The objective of this study was to investigate the prevalence of hyperhomocysteinemia and its possible clinical and laboratorial

  19. Iron-Deficiency Anemia

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    Full Text Available ... fatigue or tiredness, shortness of breath, or chest pain. If your doctor diagnoses you with iron-deficiency ... Common symptoms of iron-deficiency anemia include: Chest pain Coldness in the hands and feet Difficulty concentrating ...

  20. Iron-Deficiency Anemia

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    Full Text Available ... heart failure . Increased risk of infections Motor or cognitive development delays in children Pregnancy complications, such as ... for iron-deficiency anemia. Learn about exciting research areas that NHLBI is exploring about iron-deficiency anemia. ...

  1. Factor VII deficiency

    Science.gov (United States)

    ... this page: //medlineplus.gov/ency/article/000548.htm Factor VII deficiency To use the sharing features on this page, please enable JavaScript. Factor VII (seven) deficiency is a disorder caused by a ...

  2. Iron-Deficiency Anemia

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    Full Text Available ... deficiency anemia can cause serious complications, including heart failure and development delays in children. Explore this Health ... lead to iron-deficiency anemia include: End-stage kidney failure, where there is blood loss during dialysis. ...

  3. Iron-Deficiency Anemia

    Medline Plus

    Full Text Available ... for iron-deficiency anemia. Lifestyle habits Certain lifestyle habits may increase your risk for iron-deficiency anemia, including: Vegetarian or vegan eating patterns. Not eating enough iron-rich foods, such ...

  4. Iron-Deficiency Anemia

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    Full Text Available ... deficiency anemia can cause serious complications, including heart failure and development delays in children. Explore this Health ... to iron-deficiency anemia include: End-stage kidney failure, where there is blood loss during dialysis. People ...

  5. Iron-Deficiency Anemia

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    Full Text Available ... view the colon directly. What if my doctor thinks something else is causing my iron-deficiency anemia? ... deficiency anemia early in life affects later behavior, thinking, and mood during adolescence. Treating anemia in premature ...

  6. Iron-Deficiency Anemia

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    Full Text Available ... mg and women need 18 mg. After age 51, both men and women need 8 mg. Pregnant ... for iron-deficiency anemia. Learn about exciting research areas that NHLBI is exploring about iron-deficiency anemia. ...

  7. Iron-Deficiency Anemia

    Medline Plus

    Full Text Available ... iron-deficiency anemia. These conditions include: Intestinal and digestive conditions, such as celiac disease; inflammatory bowel diseases, ... iron-deficiency anemia , such as bleeding in the digestive or urinary tract or heavy menstrual bleeding, your ...

  8. Iron-Deficiency Anemia

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    Full Text Available ... conditions that can cause iron-deficiency anemia. Blood tests to screen for iron-deficiency anemia To screen ... the size of your liver and spleen. Blood tests Based on results from blood tests to screen ...

  9. Iron-Deficiency Anemia

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    Full Text Available ... from developing iron-deficiency anemia. Foods that are good sources of iron include dried beans, dried fruits, eggs, lean red meat, ... signs of iron-deficiency anemia include: Brittle nails ...

  10. Iron-Deficiency Anemia

    Medline Plus

    Full Text Available ... your doctor may recommend you eat heart-healthy foods or control other conditions that can cause iron-deficiency anemia. Blood tests to screen for iron-deficiency anemia To screen ...

  11. Fire Safety Deficiencies

    Data.gov (United States)

    U.S. Department of Health & Human Services — A list of all fire safety deficiencies currently listed on Nursing Home Compare, including the nursing home that received the deficiency, the associated inspection...

  12. Iron-Deficiency Anemia

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    Full Text Available ... learning how having iron-deficiency anemia early in life affects later behavior, thinking, and mood during adolescence. ... iron-deficiency anemia in blood donors affects the quality of donated red blood cells, such as how ...

  13. Iron-Deficiency Anemia

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    Full Text Available ... iron-deficiency anemia in blood donors affects the quality of donated red blood cells, such as how ... Cells From Iron-deficient Donors: Recovery and Storage Quality. Learn more about participating in a clinical trial . ...

  14. Iron-Deficiency Anemia

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    Full Text Available ... leaving cells where it is stored or from being absorbed in the duodenum, the first part of ... treatments for iron-deficiency anemia. Living With After being diagnosed with iron-deficiency anemia, it is important ...

  15. Iron-Deficiency Anemia

    Medline Plus

    Full Text Available ... if you are diagnosed with iron-deficiency anemia. Risk Factors You may have an increased risk for iron-deficiency anemia because of your age, ... or sex. Age You may be at increased risk for iron deficiency at certain ages: Infants between ...

  16. Iron-Deficiency Anemia

    Medline Plus

    Full Text Available ... Home / < Back To Health Topics / Iron-Deficiency Anemia Iron-Deficiency Anemia Also known as Leer en español ... bleeding Consuming less than recommended daily amounts of iron Iron-deficiency anemia can be caused by getting ...

  17. Iron-Deficiency Anemia

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    Full Text Available ... Topics News & Resources Intramural Research Home / < Back To Health Topics / Iron-Deficiency Anemia Iron-Deficiency Anemia Also known as Leer ... and symptoms as well as complications from iron-deficiency anemia. Research for Your Health The NHLBI is part of the U.S. Department ...

  18. Iron-Deficiency Anemia

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    Full Text Available ... anemia, your doctor may order the following blood tests to diagnose iron-deficiency anemia: Complete blood count (CBC) to ... than normal when viewed under a microscope. Different tests help your doctor diagnose iron-deficiency anemia. In iron-deficiency anemia, blood ...

  19. Iron-Deficiency Anemia

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    Full Text Available ... for iron-deficiency anemia if you have certain risk factors , including pregnancy. To prevent iron-deficiency anemia, your doctor may recommend you eat heart-healthy foods or control other conditions that can cause iron-deficiency anemia. ...

  20. Carnitine Deficiency and Pregnancy

    Directory of Open Access Journals (Sweden)

    Anouk de Bruyn

    2015-01-01

    Full Text Available We present two cases of carnitine deficiency in pregnancy. In our first case, systematic screening revealed L-carnitine deficiency in the first born of an asymptomatic mother. In the course of her second pregnancy, maternal carnitine levels showed a deficiency as well. In a second case, a mother known with carnitine deficiency under supplementation was followed throughout her pregnancy. Both pregnancies had an uneventful outcome. Because carnitine deficiency can have serious complications, supplementation with carnitine is advised. This supplementation should be continued throughout pregnancy according to plasma concentrations.

  1. Iron-Deficiency Anemia

    Medline Plus

    Full Text Available ... increased need for iron during growth spurts. Older adults, especially those over age ... athletes. Athletes, especially young females, are at risk for iron deficiency. Endurance ...

  2. Iodine deficiency disorders

    Energy Technology Data Exchange (ETDEWEB)

    Ali, S M [Pakistan Council for Science and Technology, Islamabad (Pakistan)

    1994-12-31

    Iodine deficiency (IDD) is one of the common problem in the diet. Iodine deficiency as prevalence of goiter in population occurs in the mountainous areas. There is consensus that 800 million people are at risk of IDD from living in iodine deficient area and 190 million from goiter. Very high prevalence of IDD in different parts of the world are striking. It has generally observed that in iodine-deficient areas about 50% are affected with goiter, 1-5% from cretinsim and 20% from impaired mental and/or mortor function. (A.B.).

  3. Iron-Deficiency Anemia

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    Full Text Available ... Small Business Innovation Research (SBIR) and Small Business Technology Transfer (STTR) programs. Our ... more information about Donor Iron Deficiency Study - Red Blood Cells ...

  4. Amnionless function is required for cubilin brush-border expression and intrinsic factor-cobalamin (vitamin B12) absorption in vivo

    Science.gov (United States)

    He, Qianchuan; Madsen, Mette; Kilkenney, Adam; Gregory, Brittany; Christensen, Erik I.; Vorum, Henrik; Højrup, Peter; Schäffer, Alejandro A.; Kirkness, Ewen F.; Tanner, Stephan M.; de la Chapelle, Albert; Giger, Urs; Moestrup, Søren K.; Fyfe, John C.

    2005-01-01

    Amnionless (AMN) and cubilin gene products appear to be essential functional subunits of an endocytic receptor called cubam. Mutation of either gene causes autosomal recessive Imerslund-Gräsbeck syndrome (I-GS, OMIM no. 261100) in humans, a disorder characterized by selective intestinal malabsorption of cobalamin (vitamin B12) and urinary loss of several specific low-molecular-weight proteins. Vital insight into the molecular pathology of I-GS has been obtained from studies of dogs with a similar syndrome. In this work, we show that I-GS segregates in a large canine kindred due to an in-frame deletion of 33 nucleotides in exon 10 of AMN. In a second, unrelated I-GS kindred, affected dogs exhibit a homozygous substitution in the AMN translation initiation codon. Studies in vivo demonstrated that both mutations abrogate AMN expression and block cubilin processing and targeting to the apical membrane. The essential features of AMN dysfunction observed in vivo are recapitulated in a heterologous cell-transfection system, thus validating the system for analysis of AMN-cubilin interactions. Characterization of canine AMN mutations that cause I-GS establishes the canine model as an ortholog of the human disorder well suited to studies of AMN function and coevolution with cubilin. (Blood. 2005;106:1447-1453) PMID:15845892

  5. Alternatively Spliced Methionine Synthase in SH-SY5Y Neuroblastoma Cells: Cobalamin and GSH Dependence and Inhibitory Effects of Neurotoxic Metals and Thimerosal

    Directory of Open Access Journals (Sweden)

    Mostafa Waly

    2016-01-01

    Full Text Available The folate and cobalamin (Cbl- dependent enzyme methionine synthase (MS is highly sensitive to oxidation and its activity affects all methylation reactions. Recent studies have revealed alternative splicing of MS mRNA in human brain and patient-derived fibroblasts. Here we show that MS mRNA in SH-SY5Y human neuroblastoma cells is alternatively spliced, resulting in three primary protein species, thus providing a useful model to examine cofactor dependence of these variant enzymes. MS activity was dependent upon methylcobalamin (MeCbl or the combination of hydroxocobalamin (OHCbl and S-adenosylmethionine (SAM. OHCbl-based activity was eliminated by depletion of the antioxidant glutathione (GSH but could be rescued by provision of either glutathionylcobalamin (GSCbl or MeCbl. Pretreatment of cells with lead, arsenic, aluminum, mercury, or the ethylmercury-containing preservative thimerosal lowered GSH levels and inhibited MS activity in association with decreased uptake of cysteine, which is rate-limiting for GSH synthesis. Thimerosal treatment decreased cellular levels of GSCbl and MeCbl. These findings indicate that the alternatively spliced form of MS expressed in SH-SY5Y human neuronal cells is sensitive to inhibition by thimerosal and neurotoxic metals, and lower GSH levels contribute to their inhibitory action.

  6. Influence of folic acid, pyridoxal phosphate and cobalamin on plasma homocyst(e)ine levels and the susceptibility of low-density lipoprotein to ex-vivo oxidation.

    Science.gov (United States)

    Weiss, N; Feussner, A; Hailer, S; Spengel, F A; Keller, C; Wolfram, G

    1999-10-15

    Mild hyperhomocyst(e)inaemia is a risk factor for atherosclerotic vascular disease. In-vitro studies have shown that autooxidation of homocyst(e)ine is accompanied by the generation of oxygen radicals. This may lead to oxidative modification of low-density lipoproteins (LDL) and promote atherosclerotic vascular lesions. In male patients with peripheral arterial occlusive disease we determined fasting and post methionine load homocyst(e)ine levels by high performance liquid chromatography and the susceptibility of their LDL particles to ex-vivo oxidation by continously measuring the conjugated diene production induced by incubation with copper ions. Oxidation resistance (expressed as lag time), maximal oxidation rate, and extent of oxidation (expressed of total diene production) of LDL from patients with normal or mildly elevated homocyst(e)ine levels did not differ significantly. Folic acid, pyridoxal phosphate and cobalamin supplementation significantly decreased plasma homocyst(e)ine levels in hyperhomocyst(e)inaemic patients. This went along with a significant decrease in the extent of LDL oxidation and additionally increased HDL-cholesterol levels. The clinical relevance of these findings for the long-term course of atherosclerotic vascular disorders has to be determined by intervention studies.

  7. Iron-Deficiency Anemia

    Medline Plus

    Full Text Available ... exploring about iron-deficiency anemia. Read more New treatments for disorders that lead to iron-deficiency anemia. We are ... and other pathways. This could help develop new therapies for conditions that ... behavior, thinking, and mood during adolescence. Treating anemia in ...

  8. Muscle phosphorylase kinase deficiency

    DEFF Research Database (Denmark)

    Preisler, N; Orngreen, M C; Echaniz-Laguna, A

    2012-01-01

    To examine metabolism during exercise in 2 patients with muscle phosphorylase kinase (PHK) deficiency and to further define the phenotype of this rare glycogen storage disease (GSD).......To examine metabolism during exercise in 2 patients with muscle phosphorylase kinase (PHK) deficiency and to further define the phenotype of this rare glycogen storage disease (GSD)....

  9. Iron-Deficiency Anemia

    Medline Plus

    Full Text Available ... loss and lead to iron-deficiency anemia. Common causes of blood loss that lead to iron-deficiency anemia include: Bleeding in your GI tract, from an ulcer, colon cancer, or regular use of medicines such as aspirin ...

  10. Iron-Deficiency Anemia

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    Full Text Available ... iron-deficiency anemia. Search the NIH Research Portfolio Online Reporting Tools (RePORT) to learn about research that ... iron-deficiency anemia in blood donors affects the quality of donated red blood cells, such as how ...

  11. Iron-Deficiency Anemia

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    Full Text Available ... blocks the intestine from taking up iron. Other medical conditions Other medical conditions that may lead to iron-deficiency anemia ... daily amount of iron. If you have other medical conditions that cause iron-deficiency anemia , such as ...

  12. Iron-Deficiency Anemia

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    Full Text Available ... anemia if you have certain risk factors , including pregnancy. To prevent iron-deficiency anemia, your doctor may recommend you eat heart-healthy foods or control other conditions that can cause iron-deficiency anemia. Blood tests to screen for ...

  13. Iron-Deficiency Anemia

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    Full Text Available ... Are you curious about how inflammation from chronic diseases can cause iron-deficiency anemia? Read more When there is ... DBDR) is a leader in research on the causes, prevention, and treatment of blood diseases, including iron-deficiency anemia. Search the NIH Research ...

  14. Nutritional iron deficiency

    NARCIS (Netherlands)

    Zimmermann, M.B.; Hurrell, R.F.

    2007-01-01

    Iron deficiency is one of the leading risk factors for disability and death worldwide, affecting an estimated 2 billion people. Nutritional iron deficiency arises when physiological requirements cannot be met by iron absorption from diet. Dietary iron bioavailability is low in populations consuming

  15. Iron-Deficiency Anemia

    Medline Plus

    Full Text Available ... Topics section only, or the News and Resources section. NHLBI Entire Site NHLBI Entire Site Health ... español Iron-deficiency anemia is a common type of anemia that occurs if you do not have enough iron in your body. People with mild or moderate iron-deficiency anemia ...

  16. Iron-Deficiency Anemia

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    Full Text Available ... for iron-deficiency anemia. Lifestyle habits Certain lifestyle habits may increase your risk for iron-deficiency anemia, including: Vegetarian or vegan eating patterns. Not eating enough iron-rich foods, such as meat and fish, may result in ...

  17. Iron-Deficiency Anemia

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    Full Text Available ... blood cells. Iron-deficiency anemia usually develops over time because your body’s intake of iron is too ... clamping of your newborn’s umbilical cord at the time of delivery. This may help prevent iron-deficiency ...

  18. Iron-Deficiency Anemia

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    Full Text Available ... other conditions that can cause iron-deficiency anemia. Blood tests to screen for iron-deficiency anemia To screen ... check the size of your liver and spleen. Blood tests Based on results from blood tests to screen ...

  19. Iron-Deficiency Anemia

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    Full Text Available ... also are hoping to determine which iron supplements work best to treat iron-deficiency anemia in children who do not consume the daily recommended amount of iron. Read less Participate in NHLBI Clinical Trials We lead or sponsor many studies related to iron-deficiency anemia. See if you ...

  20. Iron-Deficiency Anemia

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    Full Text Available ... en español Iron-deficiency anemia is a common type of anemia that occurs if you do not ... iron-deficiency anemia and help rule out other types of anemia. Treatment will explain treatment-related complications ...

  1. Iron deficiency in childhood

    NARCIS (Netherlands)

    Uijterschout, L.

    2015-01-01

    Iron deficiency (ID) is the most common micronutrient deficiency in the world. Iron is involved in oxygen transport, energy metabolism, immune response, and plays an important role in brain development. In infancy, ID is associated with adverse effects on cognitive, motor, and behavioral development

  2. Iron-Deficiency Anemia

    Medline Plus

    Full Text Available ... anemia. Return to Signs, Symptoms, and Complications to review signs and symptoms as well as complications from iron-deficiency ... NIH]) Heavy Menstrual Bleeding (Centers for Disease Control and ... Dietary Supplement Fact Sheet (NIH) Iron-Deficiency Anemia (National Library ...

  3. Iron deficiency anemia

    Science.gov (United States)

    Anemia - iron deficiency ... iron from old red blood cells. Iron deficiency anemia develops when your body's iron stores run low. ... You may have no symptoms if the anemia is mild. Most of the time, ... slowly. Symptoms may include: Feeling weak or tired more often ...

  4. Iron-Deficiency Anemia

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    Full Text Available ... be at risk for iron-deficiency anemia. Lifestyle habits Certain lifestyle habits may increase your risk for iron-deficiency anemia, ... you are experiencing side effects such as a bad metallic taste, vomiting, diarrhea, constipation, or upset stomach. ...

  5. Iron-Deficiency Anemia

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    Full Text Available ... how we are using current research and advancing research to prevent iron-deficiency anemia. Participate in NHLBI Clinical Trials will explain our ongoing clinical studies that are investigating prevention strategies for iron-deficiency anemia. Signs, Symptoms, and Complications ...

  6. Metabolic pathways leading to hyperhomocysteinemia

    Czech Academy of Sciences Publication Activity Database

    Šenholdová, Z.; Navrátil, Tomáš; Přistoupilová, K.; Přistoupil, T. I.; Heyrovský, Michael; Kohlíková, E.; Petr, M.

    2005-01-01

    Roč. 9, 3-4 (2005), s. 93-96 ISSN 1335-2253 R&D Projects: GA MPO 1H-PK/42; GA MZd NR8107 Grant - others:Univerzita Karlova(CZ) 534 Institutional research plan: CEZ:AV0Z40400503 Keywords : urine * voltammetry * thiodiglycolic acid * TDGA Subject RIV: CF - Physical ; Theoretical Chemistry

  7. Milder clinical and biochemical phenotypes associated with the c.482G>A (p.Arg161Gln) pathogenic variant in cobalamin C disease: Implications for management and screening.

    Science.gov (United States)

    Almannai, Mohammed; Marom, Ronit; Divin, Kristian; Scaglia, Fernando; Sutton, V Reid; Craigen, William J; Lee, Brendan; Burrage, Lindsay C; Graham, Brett H

    2017-09-01

    Cobalamin C disease is a multisystemic disease with variable manifestations and age of onset. Genotype-phenotype correlations are well-recognized in this disorder. Here, we present a large cohort of individuals with cobalamin C disease, several of whom are heterozygous for the c.482G>A pathogenic variant (p.Arg161Gln). We compared clinical characteristics of individuals with this pathogenic variant to those who do not have this variant. To our knowledge, this study represents the largest single cohort of individuals with the c.482G>A (p.Arg161Gln) pathogenic variant. A retrospective chart review of 27 individuals from 21 families with cobalamin C disease who are followed at our facility was conducted. 13 individuals (48%) are compound heterozygous with the c.482G>A (p.Arg161Gln) on one allele and a second pathogenic variant on the other allele. Individuals with the c.482G>A (p.Arg161Gln) pathogenic variant had later onset of symptoms and easier metabolic control. Moreover, they had milder biochemical abnormalities at presentation which likely contributed to the observation that 4 individuals (31%) in this group were missed by newborn screening. The c.482G>A (p.Arg161Gln) pathogenic variant is associated with milder disease. These individuals may not receive a timely diagnosis as they may not be identified on newborn screening or because of unrecognized, late onset symptoms. Despite the milder presentation, significant complications can occur, especially if treatment is delayed. Copyright © 2017 Elsevier Inc. All rights reserved.

  8. Vitamin B12 deficiency

    DEFF Research Database (Denmark)

    Green, Ralph; Allen, Lindsay H; Bjørke-Monsen, Anne-Lise

    2017-01-01

    , subclinical deficiency affects between 2.5% and 26% of the general population depending on the definition used, although the clinical relevance is unclear. B12 deficiency can affect individuals at all ages, but most particularly elderly individuals. Infants, children, adolescents and women of reproductive age...... remain debated. Management depends on B12 supplementation, either via high-dose oral routes or via parenteral administration. This Primer describes the current knowledge surrounding B12 deficiency, and highlights improvements in diagnostic methods as well as shifting concepts about the prevalence, causes...

  9. Co-ordinate variations in methylmalonyl-CoA mutase and methionine synthase, and the cobalamin cofactors in human glioma cells during nitrous oxide exposure and the subsequent recovery phase.

    Science.gov (United States)

    Riedel, B; Fiskerstrand, T; Refsum, H; Ueland, P M

    1999-07-01

    We investigated the co-ordinate variations of the two cobalamin (Cbl)-dependent enzymes, methionine synthase (MS) and methylmalonyl-CoA mutase (MCM), and measured the levels of their respective cofactors, methylcobalamin (CH3Cbl) and adenosylcobalamin (AdoCbl) in cultured human glioma cells during nitrous oxide exposure and during a subsequent recovery period of culture in a nitrous oxide-free atmosphere (air). In agreement with published data, MS as the primary target of nitrous oxide was inactivated rapidly (initial rate of 0.06 h(-1)), followed by reduction of CH3Cbl (to ordinate distribution of Cbl cofactors during depletion and repletion.

  10. Prevalence of mild serum vitamin B12 deficiency in rural and urban Costa Rican young adults Prevalencia de la deficiencia moderada de vitamina B12 sérica en jóvenes adultos de zonas rurales y urbanas de Costa Rica

    Directory of Open Access Journals (Sweden)

    Ileana Holst-Schumacher

    2007-12-01

    Full Text Available OBJECTIVE: Recent studies have shown an increase of mild serum cobalamin (vitamin B12 deficiency in some Latin American countries; however, no data are available from Costa Rica. The purpose of this work was to establish the prevalence of serum vitamin B12 deficiency among Costa Rican young adults and to study some factors that may help explain the serum cobalamin concentrations. METHODS: A cross-sectional survey was conducted among 400 adults aged 20 to 40 years old from urban and rural areas of the central valley of Costa Rica to determine serum vitamin B12 levels. Additionally, cobalamin dietary intake and the detection of Helicobacter pylori IgG antibodies were studied as possible determinants of the serum vitamin B12 concentrations. RESULTS: The mean serum concentration of vitamin B12 was 268 ± 125 pmol/L, and no significant differences were found by gender or area. Study data indicate an overall prevalence of inadequate serum cobalamin levels of 42.4% (11.2% deficient and 31.2% marginal; more than 50% but less than 75% of individuals had an intake of vitamin B12 below the U.S. Estimated Average Requirement (EAR and 61.2% had IgG antibodies to H. pylori. CONCLUSIONS: The prevalence of mild serum vitamin B12 deficiency in young Costa Rican subjects is as high as in other Latin American countries. More investigation should be done to elucidate the etiological factors that are generating deficient and marginal serum cobalamin levels in Costa Rican adults in order to define appropriate public health actions.OBJETIVO: Aunque estudios recientes han demostrado un incremento en el déficit moderado de cobalamina (vitamina B12 sérica en algunos países de América Latina, no hay datos de Costa Rica. El propósito de este trabajo fue determinar la prevalencia de la deficiencia de vitamina B12 sérica en jóvenes adultos de Costa Rica y estudiar algunos factores que pueden ayudar a explicar las concentraciones séricas de cobalamina. MÉTODOS: Se

  11. Cryopreservation studies of an artificial co-culture between the cobalamin-requiring green alga Lobomonas rostrata and the bacterium Mesorhizobium loti.

    Science.gov (United States)

    Ridley, Christian J A; Day, John G; Smith, Alison G

    2018-01-01

    Algal-bacterial co-cultures, rather than cultures of algae alone, are regarded as having the potential to enhance productivity and stability in industrial algal cultivation. As with other inocula in biotechnology, to avoid loss of production strains, it is important to develop preservation methods for the long-term storage of these cultures, and one of the most commonly used approaches is cryopreservation. However, whilst there are many reports of cryopreserved xenic algal cultures, little work has been reported on the intentional preservation of both algae and beneficial bacteria in xenic cultures. Instead, studies have focused on the development of methods to conserve the algal strain(s) present, or to avoid overgrowth of bacteria in xenic isolates during the post-thaw recovery phase. Here, we have established a co-cryopreservation method for the long-term storage of both partners in a unialgal-bacterial co-culture. This is an artificial model mutualism between the alga Lobomonas rostrata and the bacterium Mesorhizobium loti , which provides vitamin B 12 (cobalamin) to the alga in return for photosynthate. Using a Planer Kryo 360 controlled-rate cooler, post-thaw viability (PTV) values of 72% were obtained for the co-culture, compared to 91% for the axenic alga. The cultures were successfully revived after 6 months storage in liquid nitrogen, and continued to exhibit mutualism. Furthermore, the alga could be cryopreserved with non-symbiotic bacteria, without bacterial overgrowth occurring. It was also possible to use less controllable passive freezer chambers to cryopreserve the co-cultures, although the PTV was lower. Finally, we demonstrated that an optimised cryopreservation method may be used to prevent the overgrowth potential of non-symbiotic, adventitious bacteria in both axenic and co-cultures of L. rostrata after thawing.

  12. Impaired mitochondrial function in HepG2 cells treated with hydroxy-cobalamin[c-lactam]: A cell model for idiosyncratic toxicity

    International Nuclear Information System (INIS)

    Haegler, Patrizia; Grünig, David; Berger, Benjamin; Krähenbühl, Stephan; Bouitbir, Jamal

    2015-01-01

    The vitamin B12 analog hydroxy-cobalamin[c-lactam] (HCCL) impairs mitochondrial protein synthesis and the function of the electron transport chain. Our goal was to establish an in vitro model for mitochondrial dysfunction in human hepatoma cells (HepG2), which can be used to investigate hepatotoxicity of idiosyncratic mitochondrial toxicants. For that, HepG2 cells were treated with HCCL, which inhibits the function of methylmalonyl-CoA mutase and impairs mitochondrial protein synthesis. Secondary, cells were incubated with propionate that served as source of propionyl-CoA, a percursor of methylmalonyl-CoA. Dose-finding experiments were conducted to evaluate the optimal dose and treatment time of HCCL and propionate for experiments on mitochondrial function. 50 μM HCCL was cytotoxic after exposure of HepG2 cells for 2 d and 10 and 50 μM HCCL enhanced the cytotoxicity of 100 or 1000 μM propionate. Co-treatment with HCCL (10 μM) and propionate (1000 μM) dissipated the mitochondrial membrane potential and impaired the activity of enzyme complex IV of the electron transport chain. Treatment with HCCL decreased the mRNA content of mitochondrially encoded proteins, whereas the mtDNA content remained unchanged. We observed mitochondrial ROS accumulation and decreased mitochondrial SOD2 expression. Moreover, electron microscopy showed mitochondrial swelling. Finally, HepG2 cells pretreated with a non-cytotoxic combination of HCCL (10 μM) and propionate (100 μM) were more sensitive to the mitochondrial toxicants dronedarone, benzbromarone, and ketoconazole than untreated cells. In conclusion, we established and characterized a cell model, which could be used for testing drugs with idiosyncratic mitochondrial toxicity

  13. Organometallic DNA-B12 Conjugates as Potential Oligonucleotide Vectors: Synthesis and Structural and Binding Studies with Human Cobalamin-Transport Proteins.

    Science.gov (United States)

    Mutti, Elena; Hunger, Miriam; Fedosov, Sergey; Nexo, Ebba; Kräutler, Bernhard

    2017-11-16

    The synthesis and structural characterization of Co-(dN) 25 -Cbl (Cbl: cobalamin; dN: deoxynucleotide) and Co-(dN) 39 -Cbl, which are organometallic DNA-B 12 conjugates with single DNA strands consisting of 25 and 39 deoxynucleotides, respectively, and binding studies of these two DNA-Cbl conjugates to three homologous human Cbl transporting proteins, transcobalamin (TC), intrinsic factor (IF), and haptocorrin (HC), are reported. This investigation tests the suitability of such DNA-Cbls for the task of eventual in vivo oligonucleotide delivery. The binding of DNA-Cbl to TC, IF, and HC was investigated in competition with either a fluorescent Cbl derivative and Co-(dN) 25 -Cbl, or radiolabeled vitamin B 12 ( 57 Co-CNCbl) and Co-(dN) 25 -Cbl or Co-(dN) 39 -Cbl. Binding of the new DNA-Cbl conjugates was fast and tight with TC, but poorer with HC and IF, which extends a similar original finding with the simpler DNA-Cbl, Co-(dN) 18 -Cbl. The contrasting affinities of TC versus IF and HC for the DNA-Cbl conjugates are rationalized herein by a stepwise mechanism of Cbl binding. Critical contributions to overall affinity result from gradual conformational adaptations of the Cbl-binding proteins to the DNA-Cbl, which is first bound to the respective β domains. This transition is fast with TC, but slow with IF and HC, with which weaker binding results. The invariably tight interaction of the DNA-Cbl conjugates with TC makes the Cbl moiety a potential natural vector for the specific delivery of oligonucleotide loads from the blood into cells. © 2017 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim.

  14. Iron-Deficiency Anemia

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    Full Text Available ... body to absorb iron from the gastrointestinal tract (GI tract). Blood loss When you lose blood, you ... to iron-deficiency anemia include: Bleeding in your GI tract, from an ulcer, colon cancer, or regular ...

  15. Iron-Deficiency Anemia

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    Full Text Available ... for gastrointestinal bleeding To see if gastrointestinal bleeding is causing your iron-deficiency anemia, your doctor may order the following procedures to guide treatment . Fecal ...

  16. Iron-Deficiency Anemia

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    Full Text Available ... complications, including heart failure and development delays in children. Explore this Health ... red blood cells. Iron-deficiency anemia usually develops over time because your body’s intake of iron ...

  17. Iron-Deficiency Anemia

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    Full Text Available ... Supplement Fact Sheet (NIH) Iron-Deficiency Anemia (National Library of Medicine, MedlinePlus) ... Privacy Policy Freedom of Information Act (FOIA) Accessibility Copyright and Usage No FEAR ...

  18. Iron-Deficiency Anemia

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    Full Text Available ... our clinical trials . Are you a frequent blood donor living in New York City? This study is looking at how iron-deficiency anemia in blood donors affects the quality of donated red blood cells, ...

  19. Vitamin D Deficiency

    Science.gov (United States)

    ... to other diseases. In children, it can cause rickets. Rickets is a rare disease that causes the bones ... and children are at higher risk of getting rickets. In adults, severe vitamin D deficiency leads to ...

  20. Iron-Deficiency Anemia

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    Full Text Available ... Health and Human Development, we are investigating how best to treat premature newborns with low hemoglobin levels. ... are hoping to determine which iron supplements work best to treat iron-deficiency anemia in children who ...

  1. Iron-Deficiency Anemia

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    Full Text Available ... and Strategic Vision Leadership Scientific Divisions Operations and Administration Advisory Committees Budget and Legislative Information Jobs and ... may recommend you eat heart-healthy foods or control other conditions that can cause iron-deficiency anemia. ...

  2. Iron-Deficiency Anemia

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    Full Text Available ... iron-deficiency anemia may cause the following complications: Depression Heart problems. If you do not have enough ... these usually go away within a day or two. Red blood cell transfusions. These may be used ...

  3. Iron-Deficiency Anemia

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    Full Text Available ... more. Read less Reminders Return to Causes to review how blood loss, not consuming the recommended amount ... iron-deficiency anemia. Return to Risk Factors to review family history, lifestyle, unhealthy environments, or other factors ...

  4. Iron-Deficiency Anemia

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    Full Text Available ... same for boys and girls. From birth to 6 months, babies need 0.27 mg of iron. ... for iron deficiency at certain ages: Infants between 6 and 12 months, especially if they are fed ...

  5. Iron-Deficiency Anemia

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    Full Text Available ... detect signs of iron-deficiency anemia and help rule out other types of anemia. Treatment will explain ... your blood. More testing may be needed to rule out other types of anemia. Tests for gastrointestinal ...

  6. Iron-Deficiency Anemia

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    Full Text Available ... red blood cells, called hemolysis . Hemolysis, in this case, is caused by strong muscle contractions and the ... to prevent iron-deficiency anemia. Participate in NHLBI Clinical Trials will explain our ongoing clinical studies that ...

  7. Iron-Deficiency Anemia

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    Full Text Available ... to improve health through research and scientific discovery. Improving health with current research Learn about the following ... deficiency anemia early in life affects later behavior, thinking, and mood during adolescence. Treating anemia in premature ...

  8. Iron-Deficiency Anemia

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    Full Text Available ... A-Z Clinical Trials Publications and Resources Health Education and Awareness ... If your doctor diagnoses you with iron-deficiency anemia, your treatment will depend on the cause and severity of the condition. Your ...

  9. Iron-Deficiency Anemia

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    Full Text Available ... your blood may be normal even if the total amount of iron in your body is low. ... iron-deficiency anemia in blood donors affects the quality of donated red blood cells, such as how ...

  10. Iron-Deficiency Anemia

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    Full Text Available ... interferes with the body’s ability to make hemoglobin. Family history and genetics Von Willebrand disease is an ... deficiency anemia. Return to Risk Factors to review family history, lifestyle, unhealthy environments, or other factors that ...

  11. Iron-Deficiency Anemia

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    Full Text Available ... diagnoses you with iron-deficiency anemia, your treatment will depend on the cause and severity of the ... of iron. The recommended daily amounts of iron will depend on your age, sex, and whether you ...

  12. Iron-Deficiency Anemia

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    Full Text Available ... from developing iron-deficiency anemia. Foods that are good sources of iron include dried beans, dried fruits, ... iron is needed, such as childhood and pregnancy. Good sources of iron are meat, poultry, fish, and ...

  13. Iron-Deficiency Anemia

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    Full Text Available ... A-Z Clinical Trials Publications and Resources Health Education and Awareness The Science Science Home Blood Disorders ... infancy has lasting effects. We are interested in learning how having iron-deficiency anemia early in life ...

  14. Iron-Deficiency Anemia

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    Full Text Available ... heart failure . Increased risk of infections Motor or cognitive development delays in children Pregnancy complications, such as ... iron-deficiency anemia may require intravenous (IV) iron therapy or a blood transfusion . Iron supplements Your doctor ...

  15. Iron-Deficiency Anemia

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    Full Text Available ... absorb iron and lead to iron-deficiency anemia. These conditions include: Intestinal and digestive conditions, such as ... tract. Inflammation from congestive heart failure or obesity . These chronic conditions can lead to inflammation that may ...

  16. Iron-Deficiency Anemia

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    Full Text Available ... Blood Disorders and Blood Safety Sleep Science and Sleep Disorders Lung Diseases Heart and Vascular Diseases Precision Medicine ... prevention and treatment of heart, lung, blood, and sleep disorders, including iron-deficiency anemia. Learn about the current ...

  17. Iron-Deficiency Anemia

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    Full Text Available ... iron-deficiency anemia early in life affects later behavior, thinking, and mood during adolescence. Treating anemia in ... Visit Children and Clinical Studies to hear experts, parents, and children talk about their experiences with clinical ...

  18. Factor V deficiency

    Science.gov (United States)

    ... this page: //medlineplus.gov/ency/article/000550.htm Factor V deficiency To use the sharing features on ... M. is also a founding member of Hi-Ethics and subscribes to the principles of the Health ...

  19. Factor II deficiency

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    ... this page: //medlineplus.gov/ency/article/000549.htm Factor II deficiency To use the sharing features on ... M. is also a founding member of Hi-Ethics and subscribes to the principles of the Health ...

  20. Factor X deficiency

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    ... this page: //medlineplus.gov/ency/article/000553.htm Factor X deficiency To use the sharing features on ... M. is also a founding member of Hi-Ethics and subscribes to the principles of the Health ...

  1. Iron-Deficiency Anemia

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    Full Text Available ... is caused by strong muscle contractions and the impact of feet repeatedly striking the ground, such as ... funding on iron-deficiency anemia. We stimulate high-impact research. Our Trans-Omics for Precision Medicine (TOPMed) ...

  2. Iron-Deficiency Anemia

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    Full Text Available ... may be diagnosed with iron-deficiency anemia if you have low iron or ferritin levels in your blood. More testing may be needed to rule out other types of anemia. Tests for gastrointestinal ...

  3. Iron-Deficiency Anemia

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    Full Text Available ... for your body to absorb iron from the gastrointestinal tract (GI tract). Blood loss When you lose blood, ... iron deficiency. Endurance athletes lose iron through their gastrointestinal tracts. They also lose iron through the breakdown of ...

  4. Iron-Deficiency Anemia

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    Full Text Available ... vegetables. Foods rich in vitamin C, such as oranges, strawberries, and tomatoes, may help increase your absorption ... deficiency anemia, your doctor may recommend erythropoiesis stimulating agents (esa) . These medicines stimulate the bone marrow to ...

  5. Iron-Deficiency Anemia

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    Full Text Available ... were born prematurely may be at an even higher risk, as most of a newborn’s iron stores ... men of the same age. Women are at higher risk for iron-deficiency anemia under some circumstances, ...

  6. Iron-Deficiency Anemia

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    Full Text Available ... Iron-Deficiency Anemia (National Library of Medicine, MedlinePlus) Building 31 31 Center Drive Bethesda, MD 20892 Learn ... and Usage No FEAR Act Grants and Funding Building 31 31 Center Drive Bethesda, MD 20892 Learn ...

  7. Iron-Deficiency Anemia

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    Full Text Available ... may recommend erythropoiesis stimulating agents (esa) . These medicines stimulate the bone marrow to make more red blood ... NHLBI is funding on iron-deficiency anemia. We stimulate high-impact research. Our Trans-Omics for Precision ...

  8. Iron-Deficiency Anemia

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    Full Text Available ... tests, especially in infants and small children Heavy menstrual periods Injury or surgery Urinary tract bleeding Consuming ... iron-deficiency anemia from trauma, surgery, or heavy menstrual periods. Individuals with a gene for hemophilia, including ...

  9. Iron-Deficiency Anemia

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    Full Text Available ... and naproxen Certain rare genetic conditions such as hereditary hemorrhagic telangiectasia, which causes bleeding in the bowels ... iron-deficiency anemia may cause the following complications: Depression Heart problems. If you do not have enough ...

  10. Iron-Deficiency Anemia

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    Full Text Available ... lead in their blood from their environment or water. Lead interferes with the body’s ability to make ... iron-deficiency anemia in blood donors affects the quality of donated red blood cells, such as how ...

  11. Iron-Deficiency Anemia

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    Full Text Available ... also often take other medicines—such as proton pump inhibitors, anticoagulants, or blood thinners—that may cause iron-deficiency anemia. Proton pump inhibitors interfere with iron absorption, and blood thinners ...

  12. Iron-Deficiency Anemia

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    Full Text Available ... Cells From Iron-deficient Donors: Recovery and Storage Quality. Learn more about participating in a clinical trial . View all trials from ClinicalTrials.gov . Visit Children and Clinical Studies to hear experts, parents, and ...

  13. Iron-Deficiency Anemia

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    Full Text Available ... Look for Treatment will discuss medicines and eating pattern changes that your doctors may recommend if you ... iron-deficiency anemia, including: Vegetarian or vegan eating patterns. Not eating enough iron-rich foods, such as ...

  14. Iron-Deficiency Anemia

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    Full Text Available ... girls. From birth to 6 months, babies need 0.27 mg of iron. This number goes up ... screen blood donors for low iron stores. Reliable point-of-care testing may help identify iron deficiency ...

  15. Iron-Deficiency Anemia

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    Full Text Available ... striking the ground, such as with marathon runners. Sex Girls and women between the ages of 14 ... developing iron-deficiency anemia. Foods that are good sources of iron include dried beans, dried fruits, eggs, ...

  16. Iron-Deficiency Anemia

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    Full Text Available ... increase your risk for iron-deficiency anemia, including: Vegetarian or vegan eating patterns. Not eating enough iron- ... factors , such as if you are following a vegetarian eating pattern, your doctor may recommend changes to ...

  17. Iron-Deficiency Anemia

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    Full Text Available ... deficiency anemia. Proton pump inhibitors interfere with iron absorption, and blood thinners increase the likelihood of bleeding ... oranges, strawberries, and tomatoes, may help increase your absorption of iron. If you are pregnant, talk to ...

  18. Iron-Deficiency Anemia

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    Full Text Available ... screen for iron-deficiency anemia, your doctor may order a blood test called a complete blood count ( ... your risk factors , do a physical exam, or order blood tests or other diagnostic tests. Physical exam ...

  19. Iron-Deficiency Anemia

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    Full Text Available ... duodenum, the first part of the small intestine just beyond the stomach. Even if you have enough ... clamping of your newborn’s umbilical cord at the time of delivery. This may help prevent iron-deficiency ...

  20. Iron-Deficiency Anemia

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    Full Text Available ... less than 12 g/dl for women is diagnostic of anemia. In iron-deficiency anemia, red blood ... both full-term and preterm infants. Look for Diagnosis will explain tests and procedures that your doctor ...

  1. Iron-Deficiency Anemia

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    Full Text Available ... less than 12 g/dl for women is diagnostic of anemia. In iron-deficiency anemia, red blood ... physical exam, or order blood tests or other diagnostic tests. Physical exam Your doctor may ask about ...

  2. Iron-Deficiency Anemia

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    Full Text Available ... risk for iron-deficiency anemia, including: Vegetarian or vegan eating patterns. Not eating enough iron-rich foods, ... iron-fortified foods that have iron added. Vegetarian diets can provide enough iron if you choose nonmeat ...

  3. Iron-Deficiency Anemia

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    Full Text Available ... bleeding. If undiagnosed or untreated, iron-deficiency anemia can cause serious complications, including heart failure and development ... iron is too low. Low intake of iron can happen because of blood loss, consuming less than ...

  4. Iron-Deficiency Anemia

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    Full Text Available ... improved health for people with iron-deficiency anemia. Recipient Epidemiology Donor Studies program findings help to protect blood donors . NHLBI’s Recipient Epidemiology Donor Studies (REDS) program , which began in ...

  5. Iron-Deficiency Anemia

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    Full Text Available ... a frequent blood donor living in New York City? This study is looking at how iron-deficiency ... frequently. This study is located in New York City, and is recruiting by invitation only. View more ...

  6. Iron-Deficiency Anemia

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    Full Text Available ... to 11 mg for children ages 7 to 12 months, and down to 7 mg for children ... deficiency at certain ages: Infants between 6 and 12 months, especially if they are fed only breast ...

  7. Iron-Deficiency Anemia

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    Full Text Available ... in our clinical trials . Are you a frequent blood donor living in New York City? This study is looking at how iron-deficiency anemia in blood donors affects the quality of donated red blood cells, ...

  8. Iron-Deficiency Anemia

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    Full Text Available ... iron-deficiency anemia may cause the following complications: Depression Heart problems. If you do not have enough ... prevent complications such as abnormal heart rhythms and depression. Learn the warning signs of serious complications and ...

  9. Iron-Deficiency Anemia

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    Full Text Available ... prevent complications such as abnormal heart rhythms and depression. Learn the warning signs of serious complications and ... donors for low iron stores. Reliable point-of-care testing may help identify iron deficiency before potentially ...

  10. Iron-Deficiency Anemia

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    Full Text Available ... be at risk for iron-deficiency anemia. Lifestyle habits Certain lifestyle habits may increase your risk for ... Surgery, upper endoscopy or colonoscopy, to stop bleeding. Healthy lifestyle changes To help you meet your daily ...

  11. Iron-Deficiency Anemia

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    Full Text Available ... breastfeeding women older than 18 need 9 mg. Problems absorbing iron Even if you consume the recommended ... interested in learning how having iron-deficiency anemia early in life affects later behavior, thinking, and mood ...

  12. Iron-Deficiency Anemia

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    Full Text Available ... starch. Restless legs syndrome Shortness of breath Weakness Complications Undiagnosed or untreated iron-deficiency anemia may cause ... as complete blood count and iron studies. Prevent complications over your lifetime To prevent complications from iron- ...

  13. Iron-Deficiency Anemia

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    Full Text Available ... you do not have enough iron in your body. People with mild or moderate iron-deficiency anemia ... and where to find more information. Causes Your body needs iron to make healthy red blood cells. ...

  14. Iron-Deficiency Anemia

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    Full Text Available ... iron-deficiency anemia. Learn about the current and future NHLBI efforts to improve health through research and ... blood donors. Cardiovascular Health Study identifies predictors of future health problems in older adults. The NHLBI-sponsored ...

  15. Iron-Deficiency Anemia

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    Full Text Available ... as most of a newborn’s iron stores are developed during the third trimester of pregnancy. Children between ... This makes it harder to stop bleeding and can increase the risk of iron-deficiency anemia from ...

  16. Iron-Deficiency Anemia

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    Full Text Available ... an MCV of less than 80 femtoliters (fL). Prevention strategies If you have certain risk factors , such ... explain our ongoing clinical studies that are investigating prevention strategies for iron-deficiency anemia. Signs, Symptoms, and ...

  17. Iron-Deficiency Anemia

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    Full Text Available ... Safety Sleep Science and Sleep Disorders Lung Diseases Heart and Vascular Diseases Precision Medicine Activities Obesity, Nutrition, ... iron-deficiency anemia can cause serious complications, including heart failure and development delays in children. Explore this ...

  18. Iron-Deficiency Anemia

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    Full Text Available ... symptoms. More severe iron-deficiency anemia may cause fatigue or tiredness, shortness of breath, or chest pain. ... in the hands and feet Difficulty concentrating Dizziness Fatigue, or feeling tired, is the most common symptom. ...

  19. Manganese deficiency in plants

    DEFF Research Database (Denmark)

    Schmidt, Sidsel Birkelund; Jensen, Poul Erik; Husted, Søren

    2016-01-01

    Manganese (Mn) is an essential plant micronutrient with an indispensable function as a catalyst in the oxygen-evolving complex (OEC) of photosystem II (PSII). Even so, Mn deficiency frequently occurs without visual leaf symptoms, thereby masking the distribution and dimension of the problem...... restricting crop productivity in many places of the world. Hence, timely alleviation of latent Mn deficiency is a challenge in promoting plant growth and quality. We describe here the key mechanisms of Mn deficiency in plants by focusing on the impact of Mn on PSII stability and functionality. We also address...... the mechanisms underlying the differential tolerance towards Mn deficiency observed among plant genotypes, which enable Mn-efficient plants to grow on marginal land with poor Mn availability....

  20. Iron-Deficiency Anemia

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    Full Text Available ... to learn more about iron-deficiency anemia, our role in research and clinical trials to improve health, ... of Blood Diseases and Resources (DBDR) is a leader in research on the causes, prevention, and treatment ...

  1. Iron-Deficiency Anemia

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    Full Text Available ... Treatment will explain treatment-related complications or side effects. Diagnosis Iron-deficiency anemia may be detected during ... to your doctor if you are experiencing side effects such as a bad metallic taste, vomiting, diarrhea, ...

  2. Iron-Deficiency Anemia

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    Full Text Available ... an increased risk for iron-deficiency anemia because of your age, unhealthy environments, family ... 12 months, especially if they are fed only breast milk or are fed formula that is not fortified ...

  3. Iron-Deficiency Anemia

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    Full Text Available ... blood tests, especially in infants and small children Heavy menstrual periods Injury or surgery Urinary tract bleeding ... of iron-deficiency anemia from trauma, surgery, or heavy menstrual periods. Individuals with a gene for hemophilia, ...

  4. Iron-Deficiency Anemia

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    Full Text Available ... developing iron-deficiency anemia. Foods that are good sources of iron include dried beans, dried fruits, eggs, ... is needed, such as childhood and pregnancy. Good sources of iron are meat, poultry, fish, and iron- ...

  5. Iron-Deficiency Anemia

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    Full Text Available ... Individuals with a gene for hemophilia, including symptomatic female carriers who have heavy menstrual periods, may be ... anemia. Endurance activities and athletes. Athletes, especially young females, are at risk for iron deficiency. Endurance athletes ...

  6. Iron-Deficiency Anemia

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    Full Text Available ... and Strategic Vision Leadership Scientific Divisions Operations and Administration Advisory Committees Budget and Legislative Information Jobs and ... blood cells. Iron-deficiency anemia usually develops over time because your body’s intake of iron is too ...

  7. Iron-Deficiency Anemia

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    Full Text Available ... MCV of less than 80 femtoliters (fL). Prevention strategies If you have certain risk factors , such as ... our ongoing clinical studies that are investigating prevention strategies for iron-deficiency anemia. Signs, Symptoms, and Complications ...

  8. Iron-Deficiency Anemia

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    Full Text Available ... may recommend you eat heart-healthy foods or control other conditions that can cause iron-deficiency anemia. ... heavy menstrual bleeding, your doctor will want to control these other conditions to prevent you from developing ...

  9. Iron-Deficiency Anemia

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    Full Text Available ... lead to iron-deficiency anemia include: End-stage kidney failure, where there is blood loss during dialysis. People who have chronic kidney disease also often take other medicines—such as ...

  10. Iron-Deficiency Anemia

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    Full Text Available ... may be at risk for iron-deficiency anemia. Lifestyle habits Certain lifestyle habits may increase your risk ... upper endoscopy or colonoscopy, to stop bleeding. Healthy lifestyle changes To help you meet your daily recommended ...

  11. Iron-Deficiency Anemia

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    Full Text Available ... endoscopy or colonoscopy, to stop bleeding. Healthy lifestyle changes To help you meet your daily recommended iron ... iron-deficiency anemia early in life affects later behavior, thinking, and mood during adolescence. Treating anemia in ...

  12. Iron-Deficiency Anemia

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    Full Text Available ... Chest pain Coldness in the hands and feet Difficulty concentrating Dizziness Fatigue, or feeling tired, is the ... Our support of SBIR/STTR programs is helping advance research in iron-deficiency anemia, in part by ...

  13. Iron-Deficiency Anemia

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    Full Text Available ... infancy has lasting effects. We are interested in learning how having iron-deficiency anemia early in life ... Customer Service/Center for Health Information Email Alerts Jobs and Careers Site Index About NHLBI National Institute ...

  14. Iron-Deficiency Anemia

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    Full Text Available ... family history and genetics , lifestyle habits, or sex. Age You may be at increased risk for iron ... Signs, Symptoms, and Complications Iron-deficiency anemia can range from mild to severe. People with mild or ...

  15. Iron-Deficiency Anemia

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    Full Text Available ... iron to prepare for blood loss during delivery. Screening and Prevention Your doctor may screen you for ... and symptoms of iron-deficiency anemia. Return to Screening and Prevention to review tests to screen for ...

  16. [Iron deficiency and pica].

    Science.gov (United States)

    Muñoz, J A; Marcos, J; Risueño, C E; de Cos, C; López, R; Capote, F J; Martín, M V; Gil, J L

    1998-02-01

    To study the relationship between pica and iron-lack anaemia in a series of iron-deficiency patients in order to establish the pathogenesis of such relationship. Four-hundred and thirty-three patients were analysed. Pica was studied by introducing certain diet queries into the clinical history. All patients received oral iron and were periodically controlled with the usual clinico-haematological procedures. Pica was present in 23 patients (5.3%). Eight nourishing (namely, coffee grains, almonds, chocolate, ice, lettuce, carrots, sunflower seeds and bread) and 2 non-nourishing (clay and paper) substances were involved. A second episode of pica appeared in 9 cases upon relapsing of iron deficiency. Both anaemia and pica were cured by etiologic and substitutive therapy in all instances. No clear correlation was found with either socio-economic status or pathogenetic causes of iron deficiency and pica, and no haematological differences were seen between patients with pica and those without this alteration. (1) The pathogenesis of pica is unclear, although it appears unrelated to the degree of iron deficiency. (2) According to the findings in this series, pica seems a consequence of iron deficiency rather than its cause. (3) Adequate therapy can cure both conditions, although pica may reappear upon relapse of iron deficiency.

  17. Antepartum Ornithine Transcarbamylase Deficiency

    Directory of Open Access Journals (Sweden)

    Hitoshi Nakajima

    2014-11-01

    Full Text Available Ornithine transcarbamylase deficiency (OTCD is the most common type urea cycle enzyme deficiencies. This syndrome results from a deficiency of the mitochondrial enzyme ornithine transcarbamylase, which catalyzes the conversion of ornithine and carbamoyl phosphate to citrullin. Our case was a 28-year-old female diagnosed with OTCD following neurocognitive deficit during her first pregnancy. Although hyperammonemia was suspected as the cause of the patient's mental changes, there was no evidence of chronic liver disease. Plasma amino acid and urine organic acid analysis revealed OTCD. After combined modality treatment with arginine, sodium benzoate and hemodialysis, the patient's plasma ammonia level stabilized and her mental status returned to normal. At last she recovered without any damage left.

  18. Vitamin Excess and Deficiency.

    Science.gov (United States)

    Diab, Liliane; Krebs, Nancy F

    2018-04-01

    The published literature supports the high prevalence of supplement use in children and adolescents in the United States. Pediatricians today are faced with questions from parents and patients about the benefits, safety, efficacy, and correct dose of vitamins and minerals. In this article, we review 7 vitamins with the most clinical relevance as judged by abundance in food, risks and symptoms of deficiency, and potential for toxicity. Specifically, we focus on possible clinical scenarios that can be indicative of nutritional deficiency. We synthesize and summarize guidelines from nutrition experts, various medical societies, the World Health Organization, and the American Academy of Pediatrics. © American Academy of Pediatrics, 2018. All rights reserved.

  19. Cognitive dysfunction and depression in adult kidney transplant recipients: baseline findings from the FAVORIT Ancillary Cognitive Trial (FACT)

    Science.gov (United States)

    Hyperhomocysteinemia and B-vitamin deficiency may be treatable risk factors for cognitive impairment and decline. Hyperhomocysteinemia, cognitive impairment and depression all are common in individuals with kidney disease, including kidney transplant recipient. Accordingly, we assessed the prevalenc...

  20. What Is Combined Deficiency of Vitamin K-Dependent Clotting Factors?

    Science.gov (United States)

    ... Deficiency Factor V Deficiency Combined FV & FVIII Deficiencies Factor VII Deficiency Factor X Deficiency Factor XI Deficiency Factor ... Deficiency Factor V Deficiency Combined FV & FVIII Deficiencies Factor VII Deficiency Factor X Deficiency Factor XI Deficiency Factor ...

  1. Iron-Deficiency Anemia

    Medline Plus

    Full Text Available ... grams per deciliter (g/dl) for men and less than 12 g/dl for women is diagnostic of anemia. In iron-deficiency anemia, ... blood levels of iron will be low, or less than 10 micromoles per liter (mmol/L) for both men and women. Normal levels are 10 to 30 mmol/L. ...

  2. Alpha1-antitrypsin deficiency

    DEFF Research Database (Denmark)

    Stolk, Jan; Seersholm, Niels; Kalsheker, Noor

    2006-01-01

    The Alpha One International Registry (AIR), a multinational research program focused on alpha1-antitrypsin (AAT) deficiency, was formed in response to a World Health Organization recommendation. Each of the nearly 20 participating countries maintains a national registry of patients with AAT defic...

  3. Iron-Deficiency Anemia

    Medline Plus

    Full Text Available ... is blood loss during dialysis. People who have chronic kidney disease also often take other medicines—such as proton ... reduces iron absorption. Other treatments If you have chronic kidney disease and iron-deficiency anemia, your doctor may recommend ...

  4. Iron-Deficiency Anemia

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    Full Text Available ... A-Z Clinical Trials Publications and Resources Health Education and Awareness The Science Science Home Blood Disorders ... Small Business Innovation Research (SBIR) and Small Business Technology Transfer (STTR) ... We are interested in learning how having iron-deficiency anemia early in life ...

  5. Arginase-1 deficiency.

    Science.gov (United States)

    Sin, Yuan Yan; Baron, Garrett; Schulze, Andreas; Funk, Colin D

    2015-12-01

    Arginase-1 (ARG1) deficiency is a rare autosomal recessive disorder that affects the liver-based urea cycle, leading to impaired ureagenesis. This genetic disorder is caused by 40+ mutations found fairly uniformly spread throughout the ARG1 gene, resulting in partial or complete loss of enzyme function, which catalyzes the hydrolysis of arginine to ornithine and urea. ARG1-deficient patients exhibit hyperargininemia with spastic paraparesis, progressive neurological and intellectual impairment, persistent growth retardation, and infrequent episodes of hyperammonemia, a clinical pattern that differs strikingly from other urea cycle disorders. This review briefly highlights the current understanding of the etiology and pathophysiology of ARG1 deficiency derived from clinical case reports and therapeutic strategies stretching over several decades and reports on several exciting new developments regarding the pathophysiology of the disorder using ARG1 global and inducible knockout mouse models. Gene transfer studies in these mice are revealing potential therapeutic options that can be exploited in the future. However, caution is advised in extrapolating results since the lethal disease phenotype in mice is much more severe than in humans indicating that the mouse models may not precisely recapitulate human disease etiology. Finally, some of the functions and implications of ARG1 in non-urea cycle activities are considered. Lingering questions and future areas to be addressed relating to the clinical manifestations of ARG1 deficiency in liver and brain are also presented. Hopefully, this review will spark invigorated research efforts that lead to treatments with better clinical outcomes.

  6. Iron-Deficiency Anemia

    Medline Plus

    Full Text Available ... Science Science Home Blood Disorders and Blood Safety Sleep Science and Sleep Disorders Lung Diseases Heart and Vascular Diseases Precision ... prevention and treatment of heart, lung, blood, and sleep disorders, including iron-deficiency anemia. Learn about the ...

  7. Iron-Deficiency Anemia

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    Full Text Available ... infection. A history of gastrointestinal surgery, such as weight-loss surgery—especially gastric bypass—or gastrectomy. Certain rare ... prevention and treatment of heart, lung, blood, and sleep disorders, including iron-deficiency anemia. Learn about the ...

  8. Leukocyte adhesion deficiencies

    NARCIS (Netherlands)

    van de Vijver, Edith; van den Berg, Timo K.; Kuijpers, Taco W.

    2013-01-01

    During inflammation, leukocytes play a key role in maintaining tissue homeostasis through elimination of pathogens and removal of damaged tissue. Leukocytes migrate to the site of inflammation by crawling over and through the blood vessel wall, into the tissue. Leukocyte adhesion deficiencies (ie,

  9. Iron-Deficiency Anemia

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    Full Text Available ... iron supplements work best to treat iron-deficiency anemia in children who do not consume the daily recommended amount ... and Clinical Studies to hear experts, parents, and children talk about their experiences with clinical ... Anemia Arrhythmia Blood Donation Blood Tests Blood ...

  10. Iron-Deficiency Anemia

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    Full Text Available ... Working at the NHLBI Contact and FAQs Accessible Search Form Search the NHLBI, use the drop down list to ... treatment of blood diseases, including iron-deficiency anemia. Search the NIH Research Portfolio Online Reporting Tools (RePORT) ...

  11. Iron-Deficiency Anemia

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    Full Text Available ... or even heart failure . Increased risk of infections Motor or cognitive development delays in children Pregnancy complications, ... Upper endoscopy to look for bleeding in the esophagus, stomach, and the first part of the ... blood, and sleep disorders, including iron-deficiency anemia. Learn about the current ...

  12. Iron-Deficiency Anemia

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    Full Text Available ... how having iron-deficiency anemia early in life affects later behavior, thinking, and mood during adolescence. Treating anemia in premature or very small newborns . In collaboration with the Eunice Kennedy Shriver National Institute of Child Health and Human Development, we are investigating how ...

  13. Iron deficiency in children

    African Journals Online (AJOL)

    cell and excess iron is stored as ferritin to protect the cell from oxidative ... iron deficiency has negative effects during pregnancy and in the postpartum period, which affects maternal health ... use of undiluted cow's milk and a predominant cow's milk intake in .... on bone marrow smear or biopsy for the definitive diagnosis of.

  14. Iron-Deficiency Anemia

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    Full Text Available ... Certain conditions or medicines can decrease your body’s ability to absorb iron and lead to iron-deficiency ... environment or water. Lead interferes with the body’s ability to make hemoglobin. Family history and genetics Von ...

  15. Iron-Deficiency Anemia

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    Full Text Available ... supplements. Iron supplements can change how certain medicines work. Your doctor may suggest check-ups to make sure your ... To prevent complications from iron-deficiency anemia, your doctor may ... during certain stages of life when more iron is needed, such as childhood ...

  16. Iron-Deficiency Anemia

    Medline Plus

    Full Text Available ... an MCV of less than 80 femtoliters (fL). Prevention strategies If you have certain risk factors , such as if you are following a ... unhealthy environments, or other factors that increase your risk of developing iron-deficiency ... to Screening and Prevention to review tests to screen for and strategies ...

  17. Iron-Deficiency Anemia

    Medline Plus

    Full Text Available ... Services’ National Institutes of Health (NIH)—the Nation’s biomedical research agency that makes important scientific discoveries to improve ... efforts for iron-deficiency anemia. Learn about exciting research areas that ... This could help develop new therapies for conditions that affect the balance of iron ...

  18. Iron-Deficiency Anemia

    Medline Plus

    Full Text Available ... Complications Undiagnosed or untreated iron-deficiency anemia may cause the following complications: Depression Heart problems. If you do not have enough hemoglobin-carrying red blood cells, your heart has to work harder to move oxygen-rich blood through your ...

  19. Iron-Deficiency Anemia

    Medline Plus

    Full Text Available ... the Eunice Kennedy Shriver National Institute of Child Health and Human Development, we are investigating how best to treat premature newborns with low hemoglobin levels. We also are hoping to determine which iron supplements work best to treat iron-deficiency anemia in children ...

  20. MCAD deficiency in Denmark

    DEFF Research Database (Denmark)

    Andresen, Brage Storstein; Lund, Allan Meldgaard; Hougaard, David Michael

    2012-01-01

    Medium-chain acyl-CoA dehydrogenase deficiency (MCADD) is the most common defect of fatty acid oxidation. Many countries have introduced newborn screening for MCADD, because characteristic acylcarnitines can easily be identified in filter paper blood spot samples by tandem mass spectrometry (MS/M...

  1. Iron-Deficiency Anemia

    Medline Plus

    Full Text Available ... NHLBI News NHLBI in the Press Research Features All Events Past Events Upcoming Events About NHLBI About NHLBI Home Mission and Strategic Vision ... deficient Donors: Recovery and Storage Quality. Learn more about ... trial . View all trials from ClinicalTrials.gov . Visit Children and Clinical ...

  2. Iron-Deficiency Anemia

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    Full Text Available ... A-Z Clinical Trials Publications and Resources Health Education and Awareness The Science Science Home Blood Disorders ... Small Business Innovation Research (SBIR) and Small Business Technology Transfer (STTR) programs. Our ... more information about Donor Iron Deficiency Study - Red Blood Cells ...

  3. Isolated sulfite oxidase deficiency.

    Science.gov (United States)

    Rupar, C A; Gillett, J; Gordon, B A; Ramsay, D A; Johnson, J L; Garrett, R M; Rajagopalan, K V; Jung, J H; Bacheyie, G S; Sellers, A R

    1996-12-01

    Isolated sulfite oxidase (SO) deficiency is an autosomal recessively inherited inborn error of sulfur metabolism. In this report of a ninth patient the clinical history, laboratory results, neuropathological findings and a mutation in the sulfite oxidase gene are described. The data from this patient and previously published patients with isolated sulfite oxidase deficiency and molybdenum cofactor deficiency are summarized to characterize this rare disorder. The patient presented neonatally with intractable seizures and did not progress developmentally beyond the neonatal stage. Dislocated lenses were apparent at 2 months. There was increased urine excretion of sulfite and S-sulfocysteine and a decreased concentration of plasma cystine. A lactic acidemia was present for 6 months. Liver sulfite oxidase activity was not detectable but xanthine dehydrogenase activity was normal. The boy died of respiratory failure at 32 months. Neuropathological findings of cortical necrosis and extensive cavitating leukoencephalopathy were reminiscent of those seen in severe perinatal asphyxia suggesting an etiology of energy deficiency. A point mutation that resulted in a truncated protein missing the molybdenum-binding site has been identified.

  4. Iron-Deficiency Anemia

    Medline Plus

    Full Text Available ... do not have enough iron in your body. People with mild or moderate iron-deficiency anemia may ... as a TMRPSS6 gene mutation that causes a person’s body to make too much of a hormone ...

  5. Iron-Deficiency Anemia

    Medline Plus

    Full Text Available ... anemia, including: Vegetarian or vegan eating patterns. Not eating enough iron-rich foods, such as meat and fish, may result in ... deficiency anemia, your doctor may recommend heart-healthy eating and choosing iron-rich foods, especially during certain stages of life when more ...

  6. Iron-Deficiency Anemia

    Medline Plus

    Full Text Available ... iron-deficiency anemia early in life affects later behavior, thinking, and mood during adolescence. Treating anemia in premature or very small newborns . In collaboration with the Eunice Kennedy Shriver National Institute of Child Health and Human Development, we are investigating how best to treat ...

  7. Iron-Deficiency Anemia

    Medline Plus

    Full Text Available ... iron-deficiency anemia, including: Vegetarian or vegan eating patterns. Not eating enough iron-rich foods, such as meat and fish, may result in you getting less than the recommended daily amount of iron. Frequent blood donation. Individuals who donate blood often may be ...

  8. Familial lipoprotein lipase deficiency

    Science.gov (United States)

    ... lack an enzyme called lipoprotein lipase. Without this enzyme, the body cannot break down fat from digested food. Fat particles called chylomicrons build up in the blood. Risk factors include a family history of lipoprotein lipase deficiency. The condition is usually ...

  9. Iron-Deficiency Anemia

    Medline Plus

    Full Text Available ... Activities Obesity, Nutrition, and Physical Activity Population and Epidemiology Studies Women’s Health All Science A-Z Grants ... health for people with iron-deficiency anemia. Recipient Epidemiology Donor Studies program findings help to protect blood ...

  10. Iron-Deficiency Anemia

    Medline Plus

    Full Text Available ... and save lives. We are committed to advancing science and translating discoveries into clinical practice to promote the prevention and treatment of heart, lung, blood, and sleep disorders, including iron-deficiency anemia. Learn about the current and future NHLBI efforts to improve health through ...

  11. Iron-Deficiency Anemia

    Medline Plus

    Full Text Available ... iron-deficiency anemia early in life affects later behavior, thinking, and mood during adolescence. Treating anemia in premature or very small newborns . In collaboration with the Eunice Kennedy Shriver National Institute of Child Health and Human Development, we are investigating how ...

  12. Iron-Deficiency Anemia

    Medline Plus

    Full Text Available ... with the Eunice Kennedy Shriver National Institute of Child Health and Human Development, we are investigating how best to treat premature newborns with low hemoglobin levels. We also are hoping to determine which iron supplements work best to treat iron-deficiency anemia in children ...

  13. Iron-Deficiency Anemia

    Medline Plus

    Full Text Available ... of the body. When your heart has to work harder, this can lead to several conditions: irregular heartbeats called arrhythmias , a heart murmur , an ... chronic conditions, iron-deficiency anemia can make their condition worse or result in treatments not working as well. Look for Diagnosis will discuss any ...

  14. Iron-Deficiency Anemia

    Medline Plus

    Full Text Available ... normally stores but has used up. Increase your intake of vitamin C to help your body absorb iron. Avoid drinking black tea, which reduces iron absorption. Other treatments If you have chronic kidney disease and iron-deficiency anemia, your doctor may recommend ...

  15. Iron-Deficiency Anemia

    Medline Plus

    Full Text Available ... deficiency anemia. We stimulate high-impact research. Our Trans-Omics for Precision Medicine (TOPMed) Program now includes ... Studies (REDS) program Blood Disorders and Blood Safety Trans-Omics for Precision Medicine (TOPMed) Program Non-NHLBI ...

  16. Iron-Deficiency Anemia

    Medline Plus

    Full Text Available ... Medicine (TOPMed) Program Non-NHLBI resources Anemia (National Library of Medicine, MedlinePlus) Anemia in Chronic Kidney Disease ( ... Supplement Fact Sheet (NIH) Iron-Deficiency Anemia (National Library of Medicine, MedlinePlus) Building 31 31 Center Drive ...

  17. Iodine-deficiency disorders

    NARCIS (Netherlands)

    Zimmermann, M.B.; Jooste, P.L.; Pandav, C.S.

    2008-01-01

    billion individuals worldwide have insufficient iodine intake, with those in south Asia and sub-Saharan Africa particularly affected. Iodine deficiency has many adverse effects on growth and development. These effects are due to inadequate production of thyroid hormone and are termed

  18. Iron deficiency and cognitive functions

    Directory of Open Access Journals (Sweden)

    Jáuregui-Lobera I

    2014-11-01

    Full Text Available Ignacio Jáuregui-Lobera Department of Nutrition and Bromatology, Pablo de Olavide University, Seville, Spain Abstract: Micronutrient deficiencies, especially those related to iodine and iron, are linked to different cognitive impairments, as well as to potential long-term behavioral changes. Among the cognitive impairments caused by iron deficiency, those referring to attention span, intelligence, and sensory perception functions are mainly cited, as well as those associated with emotions and behavior, often directly related to the presence of iron deficiency anemia. In addition, iron deficiency without anemia may cause cognitive disturbances. At present, the prevalence of iron deficiency and iron deficiency anemia is 2%–6% among European children. Given the importance of iron deficiency relative to proper cognitive development and the alterations that can persist through adulthood as a result of this deficiency, the objective of this study was to review the current state of knowledge about this health problem. The relevance of iron deficiency and iron deficiency anemia, the distinction between the cognitive consequences of iron deficiency and those affecting specifically cognitive development, and the debate about the utility of iron supplements are the most relevant and controversial topics. Despite there being methodological differences among studies, there is some evidence that iron supplementation improves cognitive functions. Nevertheless, this must be confirmed by means of adequate follow-up studies among different groups. Keywords: iron deficiency, anemia, cognitive functions, supplementation

  19. Adult growth hormone deficiency

    Directory of Open Access Journals (Sweden)

    Vishal Gupta

    2011-01-01

    Full Text Available Adult growth hormone deficiency (AGHD is being recognized increasingly and has been thought to be associated with premature mortality. Pituitary tumors are the commonest cause for AGHD. Growth hormone deficiency (GHD has been associated with neuropsychiatric-cognitive, cardiovascular, neuromuscular, metabolic, and skeletal abnormalities. Most of these can be reversed with growth hormone therapy. The insulin tolerance test still remains the gold standard dynamic test to diagnose AGHD. Growth hormone is administered subcutaneously once a day, titrated to clinical symptoms, signs and IGF-1 (insulin like growth factor-1. It is generally well tolerated at the low-doses used in adults. Pegylated human growth hormone therapy is on the horizon, with a convenient once a week dosing.

  20. Epidemiology of SHOX deficiency.

    Science.gov (United States)

    Nicolosi, A; Caruso-Nicoletti, M

    2010-06-01

    Deletion of short stature homeobox-containing (SHOX) gene, in the pseudoautosomal region (PAR1) of X and Y chromosomes, is an important cause of short stature. Homozygous loss of SHOX results in the more severe Langer mesomelic dysplasia, while SHOX haploinsufficiency cause a wide spectrum of short stature phenotypes, including patients with Turner syndrome, Leri Weill dyschondrosteosis (LWD), and idiopathic short stature (ISS). In Turner syndrome, haploinsufficiency of SHOX gene, as well as short stature, are present in 100%; nevertheless, SHOX deficiency accounts for only two-thirds of Turner patients' short stature. In LWD the prevalence of SHOX gene anomalies varies from 56% to 100%. This wide range might be due to different factors such as selection criteria of patients, sample size, and method used for screening SHOX mutations. The real challenge is to establish the prevalence of SHOX deficiency in ISS children given that published studies have reported this association with a very broad frequency range varying from 1.5% to 15%. An important variable in these studies is represented by the method used for screening SHOX mutations and sometimes by differences in patient selection. Short stature is present by definition in 3 out of 100 subjects; if we consider a frequency of SHOX defects of 3% among ISS, we should expect a population prevalence of 1 in 1000. This prevalence would be higher than that of GH deficiency (1:3,500) and of Turner syndrome (1:2,500 females), suggesting that SHOX deficiency could be one of the most frequent monogenetic causes of short stature.

  1. Biotin and biotinidase deficiency

    OpenAIRE

    Zempleni, Janos; Hassan, Yousef I; Wijeratne, Subhashinee SK

    2008-01-01

    Biotin is a water-soluble vitamin that serves as an essential coenzyme for five carboxylases in mammals. Biotin-dependent carboxylases catalyze the fixation of bicarbonate in organic acids and play crucial roles in the metabolism of fatty acids, amino acids and glucose. Carboxylase activities decrease substantially in response to biotin deficiency. Biotin is also covalently attached to histones; biotinylated histones are enriched in repeat regions in the human genome and appear to play a role...

  2. Axial Ligation and Redox Changes at the Cobalt Ion in Cobalamin Bound to Corrinoid Iron-Sulfur Protein (CoFeSP or in Solution Characterized by XAS and DFT.

    Directory of Open Access Journals (Sweden)

    Peer Schrapers

    Full Text Available A cobalamin (Cbl cofactor in corrinoid iron-sulfur protein (CoFeSP is the primary methyl group donor and acceptor in biological carbon oxide conversion along the reductive acetyl-CoA pathway. Changes of the axial coordination of the cobalt ion within the corrin macrocycle upon redox transitions in aqua-, methyl-, and cyano-Cbl bound to CoFeSP or in solution were studied using X-ray absorption spectroscopy (XAS at the Co K-edge in combination with density functional theory (DFT calculations, supported by metal content and cobalt redox level quantification with further spectroscopic methods. Calculation of the highly variable pre-edge X-ray absorption features due to core-to-valence (ctv electronic transitions, XANES shape analysis, and cobalt-ligand bond lengths determination from EXAFS has yielded models for the molecular and electronic structures of the cobalt sites. This suggested the absence of a ligand at cobalt in CoFeSP in α-position where the dimethylbenzimidazole (dmb base of the cofactor is bound in Cbl in solution. As main species, (dmbCoIII(OH2, (dmbCoII(OH2, and (dmbCoIII(CH3 sites for solution Cbl and CoIII(OH2, CoII(OH2, and CoIII(CH3 sites in CoFeSP-Cbl were identified. Our data support binding of a serine residue from the reductive-activator protein (RACo of CoFeSP to the cobalt ion in the CoFeSP-RACo protein complex that stabilizes Co(II. The absence of an α-ligand at cobalt not only tunes the redox potential of the cobalamin cofactor into the physiological range, but is also important for CoFeSP reactivation.

  3. Cellular uptake of metallated cobalamins

    DEFF Research Database (Denmark)

    Tran, Mai Thanh Quynh; Stürup, Stefan; Lambert, Ian Henry

    2016-01-01

    Cellular uptake of vitamin B12-cisplatin conjugates was estimated via detection of their metal constituents (Co, Pt, and Re) by inductively coupled plasma mass spectrometry (ICP-MS). Vitamin B12 (cyano-cob(iii)alamin) and aquo-cob(iii)alamin [Cbl-OH2](+), which differ in the β-axial ligands (CN...

  4. Pseudoachondroplasia with immune deficiency

    International Nuclear Information System (INIS)

    Kultursay, N.; Taneli, B.; Cavusoglu, A.

    1988-01-01

    A 5-year old boy was admitted to the hospital with failure to thrive since he was 2 years old, with weakness in his legs and a waddling gait. He has normal mental development. His parents are normal phenotypically and are unrelated. In analysing his pedigree only a grandfather is described to have waddling gait. He has a normal craniofacial appearance but a disproportionate body with normal trunk and short extremities with height below the 3rd percentile. The diagnosis of pseudoachondroplasia was made on clinical, radiological and laboratory findings. He also had immune deficiency characterised by low T-lymphocyte populations and a low level of serum immunoglobulin A. (orig.)

  5. Primary Carnitine Deficiency

    DEFF Research Database (Denmark)

    Rasmussen, Jan; Hougaard, David M; Sandhu, Noreen

    2017-01-01

    Primary carnitine deficiency (PCD) causes low levels of carnitine in patients potentially leading to metabolic and cardiac symptoms. Newborn screening for PCD is now routine in many countries by measuring carnitine levels in infants. In this study we report Apgar scores, length and weight...... scores, length and weight compared to controls. Newborns with PCD and newborns born to mothers with PCD had significantly lower levels of free carnitine (fC0) than controls. Screening algorithms focusing only on fC0 had a high rate of detection of newborns with PCD. Sample collection 4-9 days after birth...

  6. Glucose-6-phosphatase deficiency

    Directory of Open Access Journals (Sweden)

    Labrune Philippe

    2011-05-01

    Full Text Available Abstract Glucose-6-phosphatase deficiency (G6P deficiency, or glycogen storage disease type I (GSDI, is a group of inherited metabolic diseases, including types Ia and Ib, characterized by poor tolerance to fasting, growth retardation and hepatomegaly resulting from accumulation of glycogen and fat in the liver. Prevalence is unknown and annual incidence is around 1/100,000 births. GSDIa is the more frequent type, representing about 80% of GSDI patients. The disease commonly manifests, between the ages of 3 to 4 months by symptoms of hypoglycemia (tremors, seizures, cyanosis, apnea. Patients have poor tolerance to fasting, marked hepatomegaly, growth retardation (small stature and delayed puberty, generally improved by an appropriate diet, osteopenia and sometimes osteoporosis, full-cheeked round face, enlarged kydneys and platelet dysfunctions leading to frequent epistaxis. In addition, in GSDIb, neutropenia and neutrophil dysfunction are responsible for tendency towards infections, relapsing aphtous gingivostomatitis, and inflammatory bowel disease. Late complications are hepatic (adenomas with rare but possible transformation into hepatocarcinoma and renal (glomerular hyperfiltration leading to proteinuria and sometimes to renal insufficiency. GSDI is caused by a dysfunction in the G6P system, a key step in the regulation of glycemia. The deficit concerns the catalytic subunit G6P-alpha (type Ia which is restricted to expression in the liver, kidney and intestine, or the ubiquitously expressed G6P transporter (type Ib. Mutations in the genes G6PC (17q21 and SLC37A4 (11q23 respectively cause GSDIa and Ib. Many mutations have been identified in both genes,. Transmission is autosomal recessive. Diagnosis is based on clinical presentation, on abnormal basal values and absence of hyperglycemic response to glucagon. It can be confirmed by demonstrating a deficient activity of a G6P system component in a liver biopsy. To date, the diagnosis is most

  7. [Vitamin deficiencies in breastfed children due to maternal dietary deficiency

    NARCIS (Netherlands)

    Kollee, L.A.A.

    2006-01-01

    Dietary deficiencies of vitamin B12 and vitamin D during pregnancy and lactation may result in health problems in exclusively breastfed infants. Vitamin-B12 deficiency in these infants results in irritability, anorexia and failure to thrive during the first 4-8 months of life. Severe and permanent

  8. Molecular characterization of FXI deficiency.

    Science.gov (United States)

    Berber, Ergul

    2011-02-01

    Factor XI (FXI) deficiency is a rare autosomal bleeding disease associated with genetic defects in the FXI gene. It is a heterogeneous disorder with variable tendency in bleeding and variable causative FXI gene mutations. It is characterized as a cross-reacting material-negative (CRM-) FXI deficiency due to decreased FXI levels or cross-reacting material-positive (CRM+) FXI deficiency due to impaired FXI function. Increasing number of mutations has been reported in FXI mutation database, and most of the mutations are affecting serine protease (SP) domain of the protein. Functional characterization for the mutations helps to better understand the molecular basis of FXI deficiency. Prevalence of the disease is higher in certain populations such as Ashkenazi Jews. The purpose of this review is to give an overview of the molecular basis of congenital FXI deficiency.

  9. MTHFR deficiency or reduced intake of folate or choline in pregnant mice results in impaired short-term memory and increased apoptosis in the hippocampus of wild-type offspring.

    Science.gov (United States)

    Jadavji, N M; Deng, L; Malysheva, O; Caudill, M A; Rozen, R

    2015-08-06

    Genetic or nutritional disturbances in one-carbon metabolism, with associated hyperhomocysteinemia, can result in complex disorders including pregnancy complications and neuropsychiatric diseases. In earlier work, we showed that mice with a complete deficiency of methylenetetrahydrofolate reductase (MTHFR), a critical enzyme in folate and homocysteine metabolism, had cognitive impairment with disturbances in choline metabolism. Maternal demands for folate and choline are increased during pregnancy and deficiencies of these nutrients result in several negative outcomes including increased resorption and delayed development. The goal of this study was to investigate the behavioral and neurobiological impact of a maternal genetic deficiency in MTHFR or maternal nutritional deficiency of folate or choline during pregnancy on 3-week-old Mthfr(+/+) offspring. Mthfr(+/+) and Mthfr(+/-) females were placed on control diets (CD); and Mthfr(+/+) females were placed on folate-deficient diets (FD) or choline-deficient diets (ChDD) throughout pregnancy and lactation until their offspring were 3weeks of age. Short-term memory was assessed in offspring, and hippocampal tissue was evaluated for morphological changes, apoptosis, proliferation and choline metabolism. Maternal MTHFR deficiency resulted in short-term memory impairment in offspring. These dams had elevated levels of plasma homocysteine when compared with wild-type dams. There were no differences in plasma homocysteine in offspring. Increased apoptosis and proliferation was observed in the hippocampus of offspring from Mthfr(+/-) mothers. In the maternal FD and ChDD study, offspring also showed short-term memory impairment with increased apoptosis in the hippocampus; increased neurogenesis was observed in ChDD offspring. Choline acetyltransferase protein was increased in the offspring hippocampus of both dietary groups and betaine was decreased in the hippocampus of FD offspring. Our results reveal short-term memory

  10. Genetics Home Reference: factor VII deficiency

    Science.gov (United States)

    ... Facebook Twitter Home Health Conditions Factor VII deficiency Factor VII deficiency Printable PDF Open All Close All Enable Javascript to view the expand/collapse boxes. Description Factor VII deficiency is a rare bleeding disorder that varies ...

  11. Monocular Elevation Deficiency - Double Elevator Palsy

    Science.gov (United States)

    ... Español Condiciones Chinese Conditions Monocular Elevation Deficiency/ Double Elevator Palsy En Español Read in Chinese What is monocular elevation deficiency (Double Elevator Palsy)? Monocular Elevation Deficiency, also known by the ...

  12. Genetics Home Reference: CDKL5 deficiency disorder

    Science.gov (United States)

    ... Facebook Twitter Home Health Conditions CDKL5 deficiency disorder CDKL5 deficiency disorder Printable PDF Open All Close All ... Javascript to view the expand/collapse boxes. Description CDKL5 deficiency disorder is characterized by seizures that begin ...

  13. Genetics Home Reference: tyrosine hydroxylase deficiency

    Science.gov (United States)

    ... Email Facebook Twitter Home Health Conditions TH deficiency Tyrosine hydroxylase deficiency Printable PDF Open All Close All ... Javascript to view the expand/collapse boxes. Description Tyrosine hydroxylase (TH) deficiency is a disorder that primarily ...

  14. Mortality and GH deficiency

    DEFF Research Database (Denmark)

    Stochholm, Kirstine; Gravholt, Claus Højbjerg; Laursen, Torben

    2007-01-01

    into childhood onset (CO) and adult onset (AO), discriminated by an age cutoff below or above 18 years at onset of GHD. METHOD: Data on death were identified in national registries. Sex- and cause-specific mortalities were identified in CO and AO GHD when compared with controls. RESULTS: Mortality was increased......OBJECTIVE: To estimate the mortality in Denmark in patients suffering from GH deficiency (GHD). DESIGN: Mortality was analyzed in 1794 GHD patients and 8014 controls matched on age and gender. All records in GHD patients were studied and additional morbidity noted. Patients were divided...... in CO and AO GHD in both genders, when compared with controls. The hazard ratio (HR) for CO males was 8.3 (95% confidence interval (CI) 4.5-15.1) and for females 9.4 (CI 4.6-19.4). For AO males, HR was 1.9 (CI 1.7-2.2) and for females 3.4 (CI 2.9-4.0). We found a significantly higher HR in AO females...

  15. Iron deficiency - a global problem

    International Nuclear Information System (INIS)

    Ali, S.M.

    1993-01-01

    Iron deficiency is an important nutritional global problem. This paper contains summery of information gathered from a dietary survey as iron deficiency anaemia is major public health problem in many developing countries including Pakistan. Comparison of anaemia in different age group and sex versus various regions in the world are given. In Pakistan also anaemia is widespread. According to the report of Micro-Nutrient survey of Pakistan 40% of the population are found to have low level of haemoglobin, more than half of pregnant women suffered from marginal or deficient haemoglobin. (A.B.)

  16. Iron deficiency - a global problem

    Energy Technology Data Exchange (ETDEWEB)

    Ali, S M [Pakistan Council for Science and Technology, Islamabad (Pakistan)

    1994-12-31

    Iron deficiency is an important nutritional global problem. This paper contains summery of information gathered from a dietary survey as iron deficiency anaemia is major public health problem in many developing countries including Pakistan. Comparison of anaemia in different age group and sex versus various regions in the world are given. In Pakistan also anaemia is widespread. According to the report of Micro-Nutrient survey of Pakistan 40% of the population are found to have low level of haemoglobin, more than half of pregnant women suffered from marginal or deficient haemoglobin. (A.B.).

  17. Genetics Home Reference: corticosterone methyloxidase deficiency

    Science.gov (United States)

    ... hyperreninemic hypoaldosteronism steroid 18-hydroxylase deficiency steroid 18-oxidase deficiency Visser-Cost syndrome ... Potassium Test Health Topic: Adrenal Gland Disorders Health Topic: Fluid ...

  18. Genetics Home Reference: aromatase deficiency

    Science.gov (United States)

    ... to impaired female sexual development, unusual bone growth, insulin resistance, and other signs and symptoms of aromatase deficiency . In women who are pregnant with an affected fetus, excess androgens in the ...

  19. Genetics Home Reference: fumarase deficiency

    Science.gov (United States)

    ... V, Tomlinson IP. The FH mutation database: an online database of fumarate hydratase mutations involved in the MCUL (HLRCC) tumor syndrome and congenital fumarase deficiency. BMC Med Genet. 2008 Mar 25;9:20. doi: 10.1186/1471-2350- ...

  20. Genetics Home Reference: proopiomelanocortin deficiency

    Science.gov (United States)

    ... are constantly hungry, which leads to excessive feeding (hyperphagia). The babies continuously gain weight and are severely ... brain dysregulates the body's energy balance, leading to overeating and severe obesity. POMC deficiency is a rare ...

  1. Factor XII (Hageman factor) deficiency

    Science.gov (United States)

    ... this page: //medlineplus.gov/ency/article/000545.htm Factor XII (Hageman factor) deficiency To use the sharing features on this ... M. is also a founding member of Hi-Ethics and subscribes to the principles of the Health ...

  2. ALPHA,·ANTITRYPSIN DEFICIENCY*

    African Journals Online (AJOL)

    1971-02-06

    Feb 6, 1971 ... bited proteolytic enzymatic proce.s which is able to pro- duce type A ... homozygous a!pha,-antitrypsin deficiency associated with severe obstructive .... in digestion of alveolar septa producing panacinar em- physema or type A ...

  3. Iron deficiency among blood donors

    DEFF Research Database (Denmark)

    Rigas, A S; Pedersen, O B; Magnussen, K

    2017-01-01

    Blood components collected from blood donors are an invaluable part of modern-day medicine. A healthy blood donor population is therefore of paramount importance. The results from the Danish Blood Donor Study (DBDS) indicate that gender, number of previous donations, time since last donation...... and menopausal status are the strongest predictors of iron deficiency. Only little information on the health effects of iron deficiency in blood donors exits. Possibly, after a standard full blood donation, a temporarily reduced physical performance for women is observed. However, iron deficiency among blood...... donors is not reflected in a reduced self-perceived mental and physical health. In general, the high proportion of iron-deficient donors can be alleviated either by extending the inter-donation intervals or by guided iron supplementation. The experience from Copenhagen, the Capital Region of Denmark...

  4. Anemia, Iron Deficiency and Iodine Deficiency among Nepalese School Children.

    Science.gov (United States)

    Khatiwada, Saroj; Lamsal, Madhab; Gelal, Basanta; Gautam, Sharad; Nepal, Ashwini Kumar; Brodie, David; Baral, Nirmal

    2016-07-01

    To assess iodine and iron nutritional status among Nepalese school children. A cross-sectional, community based study was conducted in the two districts, Ilam (hilly region) and Udayapur (plain region) of eastern Nepal. A total of 759 school children aged 6-13 y from different schools within the study areas were randomly enrolled. A total of 759 urine samples and 316 blood samples were collected. Blood hemoglobin level, serum iron, total iron binding capacity and urinary iodine concentration was measured. Percentage of transferrin saturation was calculated using serum iron and total iron binding capacity values. The mean level of hemoglobin, serum iron, total iron binding capacity, transferrin saturation and median urinary iodine excretion were 12.29 ± 1.85 g/dl, 70.45 ± 34.46 μg/dl, 386.48 ± 62.48 μg/dl, 19.94 ± 12.07 % and 274.67 μg/L respectively. Anemia, iron deficiency and iodine deficiency (urinary iodine excretion iron deficient children. Iron deficiency and anemia are common in Nepalese children, whereas, iodine nutrition is more than adequate. Low urinary iodine excretion was common in iron deficiency and anemia.

  5. Iron-Deficiency Anemia (For Parents)

    Science.gov (United States)

    ... Videos for Educators Search English Español Iron-Deficiency Anemia KidsHealth / For Parents / Iron-Deficiency Anemia What's in ... common nutritional deficiency in children. About Iron-Deficiency Anemia Every red blood cell in the body contains ...

  6. Iodine deficiency and thyroid disorders.

    Science.gov (United States)

    Zimmermann, Michael B; Boelaert, Kristien

    2015-04-01

    Iodine deficiency early in life impairs cognition and growth, but iodine status is also a key determinant of thyroid disorders in adults. Severe iodine deficiency causes goitre and hypothyroidism because, despite an increase in thyroid activity to maximise iodine uptake and recycling in this setting, iodine concentrations are still too low to enable production of thyroid hormone. In mild-to-moderate iodine deficiency, increased thyroid activity can compensate for low iodine intake and maintain euthyroidism in most individuals, but at a price: chronic thyroid stimulation results in an increase in the prevalence of toxic nodular goitre and hyperthyroidism in populations. This high prevalence of nodular autonomy usually results in a further increase in the prevalence of hyperthyroidism if iodine intake is subsequently increased by salt iodisation. However, this increase is transient because iodine sufficiency normalises thyroid activity which, in the long term, reduces nodular autonomy. Increased iodine intake in an iodine-deficient population is associated with a small increase in the prevalence of subclinical hypothyroidism and thyroid autoimmunity; whether these increases are also transient is unclear. Variations in population iodine intake do not affect risk for Graves' disease or thyroid cancer, but correction of iodine deficiency might shift thyroid cancer subtypes toward less malignant forms. Thus, optimisation of population iodine intake is an important component of preventive health care to reduce the prevalence of thyroid disorders. Copyright © 2015 Elsevier Ltd. All rights reserved.

  7. Iron deficiency in blood donors

    Directory of Open Access Journals (Sweden)

    Rodolfo Delfini Cançado

    Full Text Available CONTEXT: Blood donation results in a substantial loss of iron (200 to 250 mg at each bleeding procedure (425 to 475 ml and subsequent mobilization of iron from body stores. Recent reports have shown that body iron reserves generally are small and iron depletion is more frequent in blood donors than in non-donors. OBJECTIVE: The aim of this study was to evaluate the frequency of iron deficiency in blood donors and to establish the frequency of iron deficiency in blood donors according to sex, whether they were first-time or multi-time donors, and the frequency of donations per year. DESIGN: From September 20 to October 5, 1999, three hundred blood donors from Santa Casa Hemocenter of São Paulo were studied. DIAGNOSTIC TESTS: Using a combination of biochemical measurements of iron status: serum iron, total iron-binding capacity, transferrin saturation index, serum ferritin and the erythrocyte indices. RESULTS: The frequency of iron deficiency in blood donors was 11.0%, of whom 5.5% (13/237 were male and 31.7% (20/63 female donors. The frequency of iron deficiency was higher in multi-time blood donors than in first-time blood donors, for male blood donors (7.6% versus 0.0%, P < 0.05 and female ones (41.5% versus 18.5%, P < 0.05. The frequency of iron deficiency found was higher among the male blood donors with three or more donations per year (P < 0.05 and among the female blood donors with two or more donations per year (P < 0.05. CONCLUSIONS: We conclude that blood donation is a very important factor for iron deficiency in blood donors, particularly in multi-time donors and especially in female donors. The high frequency of blood donors with iron deficiency found in this study suggests a need for a more accurate laboratory trial, as hemoglobin or hematocrit measurement alone is not sufficient for detecting and excluding blood donors with iron deficiency without anemia.

  8. Primary Carnitine (OCTN2) Deficiency Without Neonatal Carnitine Deficiency

    NARCIS (Netherlands)

    Boer, L. de; Kluijtmans, L.A.J.; Morava, E.

    2013-01-01

    Although the diagnosis of a primary carnitine deficiency is usually based on a very low level of free and total carnitine (free carnitine: 1-5 muM, normal 20-55 muM) (Longo et al. 2006), we detected a patient via newborn screening with a total carnitine level 67 % of the normal value. At the age of

  9. Cobalamin Concentrations in Fetal Liver Show Gender Differences: A Result from Using a High-Pressure Liquid Chromatography-Inductively Coupled Plasma Mass Spectrometry as an Ultratrace Cobalt Speciation Method.

    Science.gov (United States)

    Bosle, Janine; Goetz, Sven; Raab, Andrea; Krupp, Eva M; Scheckel, Kirk G; Lombi, Enzo; Meharg, Andrew A; Fowler, Paul A; Feldmann, Jörg

    2016-12-20

    Maternal diet and lifestyle choices may affect placental transfer of cobalamin (Cbl) to the fetus. Fetal liver concentration of Cbl reflects nutritional status with regards to vitamin B12, but at these low concentration current Cbl measurement methods lack robustness. An analytical method based on enzymatic extraction with subsequent reversed-phase-high-pressure liquid chromatography (RP-HPLC) separation and parallel ICPMS and electrospray ionization (ESI)-Orbitrap-MS to determine specifically Cbl species in liver samples of only 10-50 mg was developed using 14 pig livers. Subsequently 55 human fetal livers were analyzed. HPLC-ICPMS analysis for cobalt (Co) and Cbl gave detection limits of 0.18 ng/g and 0.88 ng/g d.m. in liver samples, respectively, with a recovery of >95%. Total Co (Co t ) concentration did not reflect the amount of Cbl or vitamin B12 in the liver. Cbl bound Co contributes only 45 ± 15% to Co t . XRF mapping and μXANES analysis confirmed the occurrence of non-Cbl cobalt in pig liver hot spots indicating particular Co. No correlations of total cobalt nor Cbl with fetal weight or weeks of gestation were found for the human fetal livers. Although no gender difference could be identified for total Co concentration, female livers were significantly higher in Cbl concentration (24.1 ± 7.8 ng/g) than those from male fetuses (19.8 ± 7.1 ng/g) (p = 0.04). This HPLC-ICPMS method was able to quantify total Co t and Cbl in fetus liver, and it was sensitive and precise enough to identify this gender difference.

  10. Genetics Home Reference: arginase deficiency

    Science.gov (United States)

    ... belongs to a class of genetic diseases called urea cycle disorders. The urea cycle is a sequence of reactions ... links) Baby's First Test GeneReview: Arginase Deficiency GeneReview: Urea Cycle Disorders Overview MedlinePlus Encyclopedia: Hereditary urea cycle abnormality National ...

  11. [Constitutional mismatch repair deficiency syndrome

    NARCIS (Netherlands)

    Jongmans, M.C.J.; Gidding, C.E.M.; Loeffen, J.; Wesseling, P.; Mensenkamp, A.; Hoogerbrugge, N.

    2015-01-01

    BACKGROUND: Constitutional mismatch repair deficiency (CMMR-D) syndrome is characterised by a significantly increased risk for developing cancer in childhood. It arises when both parents have a mutation in the same mismatch repair gene and pass it on to their child. CASE DESCRIPTION: An 8-year-old

  12. Carnitine palmityl transferase I deficiency

    NARCIS (Netherlands)

    Al-Aqeel, A. I.; Rashed, M. S.; Ruiter, J. P.; Al-Husseini, H. F.; Al-Amoudi, M. S.; Wanders, R. J.

    2001-01-01

    Carnitine palmityl transferase I is the key enzyme in the carnitine dependent transport of long chain fatty acids across the mitochondrial inner membrane and its deficiency results in a decrease rate of fatty acids beta-oxidation with decreased energy production. We reported a family of 3 affected

  13. Epigenetic Deficiencies and Replicative Stress

    DEFF Research Database (Denmark)

    Shoaib, Muhammad; Sørensen, Claus Storgaard

    2015-01-01

    Cancer cell-specific synthetic lethal interactions entail promising therapeutic possibilities. In this issue of Cancer Cell, Pfister et al. describe a synthetic lethal interaction where cancer cells deficient in H3K36me3 owing to SETD2 loss-of-function mutation are strongly sensitized to inhibiti...

  14. Management of Iron Deficiency Anemia

    Science.gov (United States)

    Jimenez, Kristine; Kulnigg-Dabsch, Stefanie

    2015-01-01

    Anemia affects one-fourth of the world’s population, and iron deficiency is the predominant cause. Anemia is associated with chronic fatigue, impaired cognitive function, and diminished well-being. Patients with iron deficiency anemia of unknown etiology are frequently referred to a gastroenterologist because in the majority of cases the condition has a gastrointestinal origin. Proper management improves quality of life, alleviates the symptoms of iron deficiency, and reduces the need for blood transfusions. Treatment options include oral and intravenous iron therapy; however, the efficacy of oral iron is limited in certain gastrointestinal conditions, such as inflammatory bowel disease, celiac disease, and autoimmune gastritis. This article provides a critical summary of the diagnosis and treatment of iron deficiency anemia. In addition, it includes a management algorithm that can help the clinician determine which patients are in need of further gastrointestinal evaluation. This facilitates the identification and treatment of the underlying condition and avoids the unnecessary use of invasive methods and their associated risks. PMID:27099596

  15. Dopamine beta-hydroxylase deficiency

    Directory of Open Access Journals (Sweden)

    Senard Jean-Michel

    2006-03-01

    Full Text Available Abstract Dopamine beta-hydroxylase (DβH deficiency is a very rare form of primary autonomic failure characterized by a complete absence of noradrenaline and adrenaline in plasma together with increased dopamine plasma levels. The prevalence of DβH deficiency is unknown. Only a limited number of cases with this disease have been reported. DβH deficiency is mainly characterized by cardiovascular disorders and severe orthostatic hypotension. First symptoms often start during a complicated perinatal period with hypotension, muscle hypotonia, hypothermia and hypoglycemia. Children with DβH deficiency exhibit reduced ability to exercise because of blood pressure inadaptation with exertion and syncope. Symptoms usually worsen progressively during late adolescence and early adulthood with severe orthostatic hypotension, eyelid ptosis, nasal stuffiness and sexual disorders. Limitation in standing tolerance, limited ability to exercise and traumatic morbidity related to falls and syncope may represent later evolution. The syndrome is caused by heterogeneous molecular alterations of the DBH gene and is inherited in an autosomal recessive manner. Restoration of plasma noradrenaline to the normal range can be achieved by therapy with the synthetic precursor of noradrenaline, L-threo-dihydroxyphenylserine (DOPS. Oral administration of 100 to 500 mg DOPS, twice or three times daily, increases blood pressure and reverses the orthostatic intolerance.

  16. [Osteomalacia and vitamin D deficiency].

    Science.gov (United States)

    Rader, C P; Corsten, N; Rolf, O

    2015-09-01

    Vitamin D and calcium deficiency has a higher incidence in the orthopedic-trauma surgery patient population than generally supposed. In the long term this can result in osteomalacia, a form of altered bone mineralization in adults, in which the cartilaginous, non-calcified osteoid does not mature to hard bone. The current value of vitamin D and its importance for bones and other body cells are demonstrated. The causes of vitamin D deficiency are insufficient sunlight exposure, a lack of vitamin D3 and calcium, malabsorption, and rare alterations of VDR signaling and phosphate metabolism. The main symptoms are bone pain, fatigue fractures, muscular cramps, muscle pain, and gait disorders, with an increased incidence of falls in the elderly. Osteopathies induced by pharmaceuticals, tumors, rheumatism or osteoporosis have to be considered as the main differential diagnoses. In addition to the recording of symptoms and medical imaging, the diagnosis of osteomalacia should be ensured by laboratory parameters. Adequate treatment consists of the high-dose intake of vitamin D3 and the replacement of phosphate if deficient. Vitamin D is one of the important hormone-like vitamins and is required in all human cells. Deficiency of vitamin D has far-reaching consequences not only for bone, but also for other organ systems.

  17. Severe vitamin B12 deficiency in an exclusively breastfed 5-month-old Italian infant born to a mother receiving multivitamin supplementation during pregnancy

    Directory of Open Access Journals (Sweden)

    Guez Sophie

    2012-06-01

    Full Text Available Abstract Background In infants, vitamin B12 deficiency may be due to an inborn error of absorption and metabolism, or nutritional problems. Case presentation An exclusively breastfed 5-month-old Italian male infant, who was born after a normal full-term pregnancy to a vegan mother who was apparently daily treated with a multivitamin oral preparation during the second and third trimester, was hospitalised because of poor weight gain, feeding difficulties, severe pallor, muscle hypotonia and somnolence. Upon admission, his weight, length and head circumference were below the third percentile, he had an enlarged liver and spleen, and showed a significant delay in developmental milestones and communicative reactions. He had a hemoglobin level of 4.7 g/dL with an MCV of 84.2 fL, a white blood cell count of 4,680/mm3, and a platelet count of 45,000/mm3. His serum vitamin B12 level was 57 pg/mL (normal value 180–500 pg/mL and serum folate level 12.8 ng/mL (normal value >3 ng/mL. The results of metabolic examinations excluded a cobalamin C disorder, whereas nutritional screening showed a serum iron concentration of 9 μg/dL and serum ferritin of 4 ng/mL. Magnetic resonance imaging of the brain showed mild dilatation of the lateral ventricles with diffuse delayed myelination. The child was diagnosed as having vitamin B12 and iron deficiency due to nutritional inadequacy and was immediately treated with packed red blood cells, intramuscular vitamin B12 injections, and iron supplementation. A few days after the start of therapy, his hemoglobin levels and other hematological parameters rapidly improved, and a clinical improvement was observed within few weeks. There was an increase in his achievement of developmental milestones, but his development was still retarded seven months after the start of therapy. Conclusion This case underlines the importance of adequately controlling maternal vitamin B12 intake during pregnancy by means of

  18. Genetics Home Reference: dihydropyrimidine dehydrogenase deficiency

    Science.gov (United States)

    ... 5-fluorouracil and capecitabine. These drugs are not broken down efficiently by people with dihydropyrimidine dehydrogenase deficiency ... of this enzyme. Because fluoropyrimidine drugs are also broken down by the dihydropyrimidine dehydrogenase enzyme, deficiency of ...

  19. Genetics Home Reference: 21-hydroxylase deficiency

    Science.gov (United States)

    ... adrenal hyperplasias that impair hormone production and disrupt sexual development. 21-hydroxylase deficiency is responsible for about 95 ... excess production of androgens leads to abnormalities of sexual development in people with 21-hydroxylase deficiency . A lack ...

  20. Genetics Home Reference: complement component 2 deficiency

    Science.gov (United States)

    ... Topic: Immune System and Disorders Health Topic: Lupus Genetic and Rare Diseases Information Center (1 link) Complement component 2 deficiency Additional NIH Resources (1 link) National Institute of Allergy and Infectious Diseases: Primary Immune Deficiency Diseases Educational Resources (6 ...

  1. Galactose Epimerase Deficiency: Expanding the Phenotype

    NARCIS (Netherlands)

    Dias Costa, Filipa; Ferdinandusse, Sacha; Pinto, Carla; Dias, Andrea; Keldermans, Liesbeth; Quelhas, Dulce; Matthijs, Gert; Mooijer, Petra A.; Diogo, Luísa; Jaeken, Jaak; Garcia, Paula

    2017-01-01

    Galactose epimerase deficiency is an inborn error of metabolism due to uridine diphosphate-galactose-4'-epimerase (GALE) deficiency. We report the clinical presentation, genetic and biochemical studies in two siblings with generalized GALE deficiency.Patient 1: The first child was born with a

  2. DNA repair deficiency in neurodegeneration

    DEFF Research Database (Denmark)

    Jeppesen, Dennis Kjølhede; Bohr, Vilhelm A; Stevnsner, Tinna V.

    2011-01-01

    Deficiency in repair of nuclear and mitochondrial DNA damage has been linked to several neurodegenerative disorders. Many recent experimental results indicate that the post-mitotic neurons are particularly prone to accumulation of unrepaired DNA lesions potentially leading to progressive...... neurodegeneration. Nucleotide excision repair is the cellular pathway responsible for removing helix-distorting DNA damage and deficiency in such repair is found in a number of diseases with neurodegenerative phenotypes, including Xeroderma Pigmentosum and Cockayne syndrome. The main pathway for repairing oxidative...... base lesions is base excision repair, and such repair is crucial for neurons given their high rates of oxygen metabolism. Mismatch repair corrects base mispairs generated during replication and evidence indicates that oxidative DNA damage can cause this pathway to expand trinucleotide repeats, thereby...

  3. Vitamin D deficiency in Fibromyalgia

    International Nuclear Information System (INIS)

    Bhatty, S.A.; Shaikh, N.A.; Irfan, M.; Kashif, S.M.; Vaswani, A.S.; Sumbhai, A.; Gunpat

    2010-01-01

    Objective: To check the Vitamin D levels in patients diagnosed as fibromyagia in our population. Methods: Study was done at Medical OPD of Civil Hospital Karachi, from January to March 2009. Female patients diagnosed as Fibromyalgia according to American College of Rheumatology (ACR) criteria and exclusion of systemic illness on examination, and normal reports of blood CP, ESR, serum calcium, phosphate and Alkaline Phosphatase, were asked to get Vitamin D levels in their serum. Vitamin D deficiency is defined as 30 ng/ml. Result: Forty female patients were included in the study. The mean age was 37.65 +- 11.5 years. Mean Vitamin D level was 17.41 +- 5.497 ng/ml. Thirty two (80%) of patients had Vitamin D deficiency, mean levels of 15.855 +- 4.918 ng/ml and 8(20%) had Vitamin D insufficiency, mean levels of 23.64 +- 2.39 ng/ml. Patients with vitamin D deficiency and age less than 45 years were 22 (68.75%), had mean vitamin D level 16.87 +- 4.48 ng/ml whereas in age ranging from 46-75 years were 10 (31.25%) had mean vitamin D level 16.09 +- 6.45 ng/ml. Conclusion: Vitamin D deficiency is frequently seen in patients diagnosed as fibromyalgia and nonspecific musculoskeletal pain in our population. Although the sample size of the study is small, but the figures are so alarming that it is an eye opener towards the need of a population based study, including normal population as well as those presenting with musculoskeletal pain. (author)

  4. Zinc Deficiency in Humans and its Amelioration

    OpenAIRE

    Yashbir Singh Shivay

    2015-01-01

    Zinc (Zn) deficiency in humans has recently received considerable attention. Global mortality in children under 5 years of age in 2004 due to Zn deficiency was estimated at 4,53,207 as against 6,66,771 for vitamin A deficiency; 20,854 for iron deficiency and 3,619 for iodine deficiency. In humans 2800-3000 proteins contain Zn prosthetic group and Zn is an integral component of zinc finger prints that regulate DNA transcription. Zinc is a Type-2 nutrient, which means that its concentration in ...

  5. Primary Carnitine (OCTN2) Deficiency Without Neonatal Carnitine Deficiency

    OpenAIRE

    de Boer, L.; Kluijtmans, L. A. J.; Morava, E.

    2012-01-01

    Although the diagnosis of a primary carnitine deficiency is usually based on a very low level of free and total carnitine (free carnitine: 1–5 μM, normal 20–55 μM) (Longo et al. 2006), we detected a patient via newborn screening with a total carnitine level 67 % of the normal value. At the age of 1 year, after interruption of carnitine supplementation for a 4-week period the carnitine profile was assessed and the free carnitine level had dropped to 10.4 μmol/l (normal: 20–55 μM) and total car...

  6. Hyperhomocysteinemia and methylenetetrahydrofolate reductase 677C→T and 1298A→C mutations in patients with inflammatory bowel disease Hiperhomocisteinemia y mutaciones de la metilentetrahidrofolato reductasa 677C→T y 1298A→C en pacientes con enfermedad inflamatoria intestinal

    Directory of Open Access Journals (Sweden)

    C. Fernández-Miranda

    2005-07-01

    Full Text Available Background: hyperhomocysteinemia has been recently described in patients with inflammatory bowel disease (IBD, that could be related to the increased risk for thrombosis that exists in this disease. The aim of this study was the assessment of hyperhomocysteinemia in patients with IBD and its relation among vitamin B12 and folate levels, and methylenetetrahydrofolate reductase (MTHFR 677C→ T and 1298A→C mutations. Patients and methods: fifty two consecutive patients with IBD were studied (29 women and 23 men; age: mean (standard deviation 41.7 [11.9] years and 186 controls with no difference in age and gender. Hyperhomocysteinemia was considered as homocysteine levels higher than mean plus two standard deviations of the control group (≥ 13 μmol/l. Results: patients had an elevated prevalence of hyperhomocysteinemia (17.3 vs. 3.7%; p = 0.002 and lower folate (7.6 [4.1] vs. 8.9 [3.7] ng/ml; p = 0.01 and B12 vitamin levels (499 [287] vs. 603 [231] pg/ml; p = 0.003. Homocysteinemia was higher (14.3 [5.8] vs. 9.1 [3.9] μmol/l; p = 0.006 in 6 patients (11.5% that had suffered thromboembolism. Frequency of MTHFR 677C→T (13.5 vs. 11.3%; p = 0.66 and 1298A→C (7.8 vs. 7.0%; p = 0.76 mutations was not increased in patients. Odds ratio (OR for IBD in hyperhomocysteinemic patient was 5.51, 95% confidence interval (CI, 1.81-16.76; p = 0.002. Hyperhomocysteinemia was negatively associated with feminine gender (OR 0.08, 95% CI 0.01-0.49; p = 0.006 and folate levels (OR 0.04, 95%CI: 0.007-0.20; p Fundamento: recientemente se ha descrito la existencia de hiperhomocisteinemia en la enfermedad inflamatoria intestinal (EII, que podría estar relacionada con el mayor riesgo de trombosis en esta enfermedad. El objetivo del estudio ha sido evaluar la hiperhomocisteinemia en los pacientes con EII y su relación con las concentraciones de vitamina B12 y folato séricos y con las mutaciones de la metilentetrahidrofolato reductasa (MTHFR 677C→T y 1298A

  7. Skin wound healing in MMP2-deficient and MMP2 / plasminogen double-deficient mice

    DEFF Research Database (Denmark)

    Frøssing, Signe; Rønø, Birgitte; Hald, Andreas

    2010-01-01

    -sensitive MMPs during wound healing. To address whether MMP2 is accountable for the galardin-induced healing deficiency in wildtype and Plg-deficient mice, incisional skin wounds were generated in MMP2 single-deficient mice and in MMP2/Plg double-deficient mice and followed until healed. Alternatively, tissue...... was isolated 7 days post wounding for histological and biochemical analyses. No difference was found in the time from wounding to overt gross restoration of the epidermal surface between MMP2-deficient and wildtype control littermate mice. MMP2/Plg double-deficient mice were viable and fertile, and displayed...... an unchallenged general phenotype resembling that of Plg-deficient mice, including development of rectal prolapses. MMP2/Plg double-deficient mice displayed a slight increase in the wound length throughout the healing period compared with Plg-deficient mice. However, the overall time to complete healing...

  8. Toward reassessing data-deficient species.

    Science.gov (United States)

    Bland, Lucie M; Bielby, Jon; Kearney, Stephen; Orme, C David L; Watson, James E M; Collen, Ben

    2017-06-01

    One in 6 species (13,465 species) on the International Union for Conservation of Nature (IUCN) Red List is classified as data deficient due to lack of information on their taxonomy, population status, or impact of threats. Despite the chance that many are at high risk of extinction, data-deficient species are typically excluded from global and local conservation priorities, as well as funding schemes. The number of data-deficient species will greatly increase as the IUCN Red List becomes more inclusive of poorly known and speciose groups. A strategic approach is urgently needed to enhance the conservation value of data-deficient assessments. To develop this, we reviewed 2879 data-deficient assessments in 6 animal groups and identified 8 main justifications for assigning data-deficient status (type series, few records, old records, uncertain provenance, uncertain population status or distribution, uncertain threats, taxonomic uncertainty, and new species). Assigning a consistent set of justification tags (i.e., consistent assignment to assessment justifications) to species classified as data deficient is a simple way to achieve more strategic assessments. Such tags would clarify the causes of data deficiency; facilitate the prediction of extinction risk; facilitate comparisons of data deficiency among taxonomic groups; and help prioritize species for reassessment. With renewed efforts, it could be straightforward to prevent thousands of data-deficient species slipping unnoticed toward extinction. © 2016 Society for Conservation Biology.

  9. Vitamin D deficiency in Europe

    DEFF Research Database (Denmark)

    Cashman, Kevin D.; Dowling, Kirsten G; Škrabáková, Zuzana

    2016-01-01

    25(OH)D values from national health/nutrition surveys. OBJECTIVE: This study applied VDSP protocols to serum 25(OH)D data from representative childhood/teenage and adult/older adult European populations, representing a sizable geographical footprint, to better quantify the prevalence of vitamin D...... is evident throughout the European population at prevalence rates that are concerning and that require action from a public health perspective. What direction these strategies take will depend on European policy but should aim to ensure vitamin D intakes that are protective against vitamin D deficiency...

  10. Muscle phosphoglycerate mutase deficiency revisited

    DEFF Research Database (Denmark)

    Naini, Ali; Toscano, Antonio; Musumeci, Olimpia

    2009-01-01

    storage disease type X and novel mutations in the gene encoding the muscle subunit of PGAM (PGAM2). DESIGN: Clinical, pathological, biochemical, and molecular analyses. SETTING: Tertiary care university hospitals and academic institutions. Patients A 37-year-old Danish man of Pakistani origin who had...... PGAM deficiency, and molecular studies revealed 2 novel homozygous mutations, a nonsense mutation and a single nucleotide deletion. Pathological studies of muscle showed mild glycogen accumulation but prominent tubular aggregates in both patients. CONCLUSIONS: We found that glycogen storage disease...

  11. Micronutrient deficiency in urban Indonesia.

    Science.gov (United States)

    Gross, R; Schultink, W

    1997-06-01

    The economic situation of Indonesia is characterized by a large increase in the gross national product which has been on average 7% annually during the last ten years. This was accompanied by rapid urbanization. With the economic improvement, "First World" and "Third World" health and nutrition problems are coexisting in Indonesia. In 1992, the most common of death cause was cardiovascular disease whereas tuberculosis was the second ranking. About 40% of the preschool children are stunted. The main stable food and energy source is rice, although the urban population has a more diverse food pattern than the rural population. In Jakarta, many children receive too late colostrum feeding and mothers are not aware about the importance of correct breastfeeding practices after delivery. Three studies had shown that about one fifth of preschool children and one fourth of elderly take micronutrient supplements. Nevertheless, micronutrient deficiencies are prevalent in Jakarta. About one third of women suffer from moderate vitamin A deficiency (plasma retinol middle class to spend more time and money to solve their own problems.

  12. Vitamin D deficiency and stroke

    Directory of Open Access Journals (Sweden)

    2012-12-01

    Full Text Available Vitamin D comprises a group of fat-soluble pro-hormones, obtained from sun exposure, food, and supplements, and it must undergo two hydroxylation reactions to be activated in the body. Several studies have shown the role of vitamin D in mineral metabolism regulation, especially calcium, phosphorus, and bone metabolism. Some factors such as inadequate vitamin intake and liver or kidney disorders can lead to vitamin D deficiency. Furthermore, vitamin D malnutrition may also be linked to susceptibility to chronic diseases such as heart failure, peripheral artery disease, high blood pressure, cognitive impairment including foggy brain and memory loss, and autoimmune diseases including diabetes type I. Recent research has revealed that low levels of vitamin D increase the risk of cardiovascular-related morbidity (Sato et al., 2004 and mortality (Pilz et al., 2008. Also, hypertension contributes to a reduction in bone mineral density and increase in the incidence of stroke and death. This article reviews the function and physiology of vitamin D and examines the effects of vitamin D deficiency on susceptibility to stroke, as a cardiovascular event, and its morbidity and subsequent mortality.

  13. New insights into iron deficiency and iron deficiency anemia.

    Science.gov (United States)

    Camaschella, Clara

    2017-07-01

    Recent advances in iron metabolism have stimulated new interest in iron deficiency (ID) and its anemia (IDA), common conditions worldwide. Absolute ID/IDA, i.e. the decrease of total body iron, is easily diagnosed based on decreased levels of serum ferritin and transferrin saturation. Relative lack of iron in specific organs/tissues, and IDA in the context of inflammatory disorders, are diagnosed based on arbitrary cut offs of ferritin and transferrin saturation and/or marker combination (as the soluble transferrin receptor/ferritin index) in an appropriate clinical context. Most ID patients are candidate to traditional treatment with oral iron salts, while high hepcidin levels block their absorption in inflammatory disorders. New iron preparations and new treatment modalities are available: high-dose intravenous iron compounds are becoming popular and indications to their use are increasing, although long-term side effects remain to be evaluated. Copyright © 2017 Elsevier Ltd. All rights reserved.

  14. Atypical B12 Deficiency with Nonresolving Paraesthesia

    Directory of Open Access Journals (Sweden)

    S. Haider

    2013-01-01

    Full Text Available Vitamin B12 deficiency can present with various hematological, gastrointestinal and neurological manifestations. We report a case of elderly female who presented with neuropathy and vitamin B12 deficiency where the final work-up revealed polyneuropathy, organomegaly, endocrinopathy, monoclonal gammopathy, and skin changes (POEMS. This case suggests that, although POEMS syndrome is a rare entity, it can present with vitamin-B12 deficiency and thus specific work up for early diagnosis of POEMS should be considered in patients with B12 deficiency unresponsive to therapy.

  15. Genetics Home Reference: isolated growth hormone deficiency

    Science.gov (United States)

    ... can be inherited? More about Inheriting Genetic Conditions Diagnosis & Management Resources Genetic Testing (4 links) Genetic Testing Registry: Ateleiotic dwarfism Genetic Testing Registry: Autosomal dominant isolated somatotropin deficiency ...

  16. Vitamin C deficiency in weanling guinea pigs

    DEFF Research Database (Denmark)

    Lykkesfeldt, Jens; Trueba, Gilberto Perez; Poulsen, Henrik E.

    2007-01-01

    Neonates are particularly susceptible to malnutrition due to their limited reserves of micronutrients and their rapid growth. In the present study, we examined the effect of vitamin C deficiency on markers of oxidative stress in plasma, liver and brain of weanling guinea pigs. Vitamin C deficiency...... increased, while protein oxidation decreased (P¼0003). The results show that the selective preservation of brain ascorbate and induction of DNA repair in vitamin C-deficient weanling guinea pigs is not sufficient to prevent oxidative damage. Vitamin C deficiency may therefore be particularly adverse during...

  17. Development of additional pituitary hormone deficiencies in pediatric patients originally diagnosed with idiopathic isolated GH deficiency

    NARCIS (Netherlands)

    W.F. Blum (Werner); C.L. Deal (Cheri Lynn); A.G. Zimmermann (Alan); E.P. Shavrikova (Elena); C.J. Child (Christopher); C.A. Quigley (Charmian); S.L.S. Drop (Stenvert); G. Cutler (Gordon); R.G. Rosenfeld (Ron)

    2014-01-01

    textabstractObjective: We assessed the characteristics of children initially diagnosed with idiopathic isolated GH deficiency (IGHD) who later developed additional (multiple) pituitary hormone deficiencies (MPHD). Design: Data were analyzed for 5805 pediatric patients with idiopathic IGHD, who were

  18. Automated deficiency letter data base

    International Nuclear Information System (INIS)

    Jones, R.D.

    1983-12-01

    An automated data base relevant to the various licensee deficiencies that accrue during the materials licensing application review process of the Nuclear Regulatory Commission (NRC) is described. A data base management system (DBMs) is used for data retrieval, file-tending, and examination of the interrelationships among the data types in the data base. Use of word processors to emulate computer terminals for the purpose of data base population (loading) and report generation is discussed. Also described is the technique used to link, for update purposes, the data base (accessed by means of SYSTEM 2000 on a CDC 6600 computer) to the NRC Material License Master File resident on the National Institutes of Health (NIH) IBM System 370 computer. A user's manual that provides easy-to-understand instructions for the nonprogramming user on how to generate ad hoc analytical reports to facilitate management decisions is also included

  19. [Constitutional mismatch repair deficiency syndrome].

    Science.gov (United States)

    Jongmans, Marjolijn C; Gidding, Corrie E; Loeffen, Jan; Wesseling, Pieter; Mensenkamp, Arjen; Hoogerbrugge, Nicoline

    2015-01-01

    Constitutional mismatch repair deficiency (CMMR-D) syndrome is characterised by a significantly increased risk for developing cancer in childhood. It arises when both parents have a mutation in the same mismatch repair gene and pass it on to their child. An 8-year-old girl was diagnosed with CMMR-D syndrome after she developed a brain tumour at the age of 4 and a T-cell non-Hodgkin lymphoma at the age of 6. She had multiple hyperpigmented skin lesions and died of myelodysplastic syndrome at the age of 11. In children with cancer CMMR-D syndrome can be recognized particularly if there are multiple primary malignancies and skin hyperpigmentations and hypopigmentations. The parents of these children are at high risk for colorectal and endometrial cancer (Lynch syndrome), amongst others.

  20. The hobbit - an unexpected deficiency.

    Science.gov (United States)

    Hopkinson, Joseph A; Hopkinson, Nicholas S

    2013-12-16

    Vitamin D has been proposed to have beneficial effects in a wide range of contexts. We investigate the hypothesis that vitamin D deficiency, caused by both aversion to sunlight and unwholesome diet, could also be a significant contributor to the triumph of good over evil in fantasy literature. Data on the dietary habits, moral attributes and martial prowess of various inhabitants of Middle Earth were systematically extracted from J R R Tolkien's novel The hobbit. Goodness and victoriousness of characters were scored with binary scales, and dietary intake and habitual sun exposure were used to calculate a vitamin D score (range, 0-4). The vitamin D score was significantly higher among the good and victorious characters (mean, 3.4; SD, 0.5) than the evil and defeated ones (mean, 0.2; SD, 0.4; P fantastic situations and whether randomised intervention trials need to be imagined.

  1. Iron Refractory Iron Deficiency Anaemia: A Rare Cause of Iron Deficiency Anaemia

    LENUS (Irish Health Repository)

    McGrath, T

    2018-01-01

    We describe the case of a 17-month-old boy with a hypochromic microcytic anaemia, refractory to oral iron treatment. After exclusion of dietary and gastrointestinal causes of iron deficiency, a genetic cause for iron deficiency was confirmed by finding two mutations in the TMPRSS6 gene, consistent with a diagnosis of iron-refractory iron deficiency anaemia (IRIDA).

  2. A defective mutant of Salmonella enterica Serovar Gallinarum in cobalamin biosynthesis is avirulent in chickens Mutante de Salmonella enterica serovar Gallinarum duplo defectivo na biossíntese de cobalamina é avirulento para aves

    Directory of Open Access Journals (Sweden)

    Jacqueline Boldrin de Paiva

    2009-09-01

    Full Text Available Salmonella enterica serovar Gallinarum (SG is a fowl typhoid agent in chickens and is a severe disease with worldwide economic impact as its mortality may reach up to 80%. It is one of a small group of serovars that typically produces typhoid-like infections in a narrow range of host species and which therefore represents a good model for human typhoid. The survival mechanisms are not considered to be virulent mechanisms but are essential for the life of the bacterium. Mutants of Salmonella Gallinarum containing defective genes, related to cobalamin biosynthesis and which Salmonella spp. has to be produced to survive when it is in an anaerobic environment, were produced in this study. Salmonella Gallinarum is an intracellular parasite. Therefore, this study could provide information about whether vitamin B12 biosynthesis might be essential to its survival in the host. The results showed that the singular deletion in cbiA or cobS genes did not interfere in the life of Salmonella Gallinarum in the host, perhaps because single deletion is not enough to impede vitamin B12 biosynthesis. It was noticed that diluted SG mutants with single deletion produced higher mortality than the wild strain of SG. When double mutation was carried out, the Salmonella Gallinarum mutant was unable to provoke mortality in susceptible chickens. This work showed that B12 biosynthesis is a very important step in the metabolism of Salmonella Gallinarum during the infection of the chickens. Further research on bacterium physiology should be carried out to elucidate the events described in this research and to assess the mutant as a vaccine strain.Salmonella enterica serovar Gallinarum (SG é o agente do tifo aviário, doença severa que provoca mortalidade em até 80% do plantel de aves. SG encontra-se entre os poucos sorotipos de Salmonella que são agentes etiológicos de enfermidade específica, à semelhança de Salmonella Typhi em seres humanos podendo, portanto, servir

  3. Ferrotherapy of iron deficiency anemia in children

    OpenAIRE

    Berezhniy V.V.; Korneva V.V.

    2016-01-01

    Present article devoted to the steps for implementation unified clinical protocol of the primary, secondary (specialized) medical care «Iron deficiency» to the practical activities of pediatricians, family physicians. The features of ferrotherapy in children of different age groups and the issues of prevention of iron deficiency states are highlighted.

  4. Circadian behaviour in neuroglobin deficient mice

    DEFF Research Database (Denmark)

    Hundahl, Christian A; Fahrenkrug, Jan; Hay-Schmidt, Anders

    2012-01-01

    on circadian behavior. Ngb-deficient and wild-type (wt) mice were placed in running wheels and their activity rhythms, endogenous period and response to light stimuli were investigated. The effect of Ngb deficiency on the expression of Period1 (Per1) and the immediate early gene Fos was determined after light...

  5. Common micronutrient deficiencies among food aid beneficiaries ...

    African Journals Online (AJOL)

    admin

    Abstract. Background: Ethiopia is amongst the African countries that have received significant food aid. Nonetheless, the common micronutrient deficiencies among food aid beneficiaries are not well documented. Objective: To find out the common micronutrient deficiencies among food aid beneficiaries in the country based ...

  6. Genetics Home Reference: lysosomal acid lipase deficiency

    Science.gov (United States)

    ... lipase deficiency develop multi-organ failure and severe malnutrition and generally do not survive past 1 year. In the later-onset form of lysosomal acid lipase deficiency , signs and symptoms vary and usually begin in mid-childhood, although they can appear anytime up to late ...

  7. Growth hormone deficiency and hyperthermia during exercise

    DEFF Research Database (Denmark)

    Juul, A; Hjortskov, N; Jepsen, Leif

    1995-01-01

    Sweat secretion is often disturbed in patients with GH secretory disorders. Hyperhidrosis is a classic feature of acromegaly, and it has recently been shown that GH-deficient patients exhibit decreased sweating capacity after pilocarpine stimulation of the skin. Thus, patients with GH-deficiency ...

  8. MARGINAL IODINE DEFICIENCY EXACERBATES PERCHLORATE THYROID TOXICITY.

    Science.gov (United States)

    The environmental contaminant perchlorate disrupts thyroid homeostasis via inhibition of iodine uptake into the thyroid. This work tested whether iodine deficiency exacerbates the effects of perchlorate. Female 27 day-old LE rats were fed a custom iodine deficient diet with 0, 50...

  9. Hematopoietic studies in vitamin A deficiency.

    Science.gov (United States)

    Hodges, R E; Sauberlich, H E; Canham, J E; Wallace, D L; Rucker, R B; Mejia, L A; Mohanram, M

    1978-05-01

    Recent studies of experimental vitamin A deficiency in man led the authors to conclude that anemia may result from lack of vitamin A. A review of numerous nutrition surveys in underdeveloped countries enhanced the suspicion that deficiency of vitamin A does contribute to the prevalence of anemia. Preliminary studies of vitamin A-deficient rats confirmed previous observations that anemia may result from lack of this vitamin. The livers of these animals had very low concentrations of vitamin A but normal or increased concentrations of iron. The finding of anemia is in contrast with other reports that vitamin A deficiency may cause elevated values for hemoglobin and hematocrit. The authors suggest that loss of taste and smell as a result of deficiency may account for refusal of experimental animals to eat and drink enough to prevent inanitation and dehydration. The resulting hemoconcentration may mask the true hematological picture, which is one of anemia.

  10. Japanese family with congenital factor VII deficiency.

    Science.gov (United States)

    Sakakibara, Kanae; Okayama, Yoshiki; Fukushima, Kenji; Kaji, Shunsaku; Muraoka, Michiko; Arao, Yujiro; Shimada, Akira

    2015-10-01

    Congenital factor VII (FVII) deficiency is a rare bleeding disorder with autosomal recessive inheritance. The present female patient was diagnosed with congenital FVII deficiency because of low hepaplastin test (HPT), although vitamin K was given. Heterozygous p.A191T mutation was detected in the peripheral blood, and the same mutation was also found in the mother and sister. To the best of our knowledge, this is the fourth reported case of p.A191T mutation of FVII in the literature and the first to be reported in Japan. FVII coagulation activity (FVII:C) in asymptomatic heterozygous carriers is mildly reduced. Therefore, some patients may not be accurately diagnosed with congenital FVII deficiency. In infants with low HPT without vitamin K deficiency, congenital FVII deficiency should be considered. © 2015 Japan Pediatric Society.

  11. Deficiency of the Chemotactic Factor Inactivator in Human Sera with α1-Antitrypsin Deficiency

    Science.gov (United States)

    Ward, Peter A.; Talamo, Richard C.

    1973-01-01

    As revealed by appropriate fractionation procedures, human serum deficient in α1-antitrypsin (α1-AT) is also deficient in the naturally occurring chemotactic factor inactivator. These serum donors had severe pulmonary emphysema. Serum from patients with clinically similar pulmonary disease, but with presence of α1-AT in the serum, showed no such deficiency of the chemotactic factor inactivator. When normal human serum and α1-AT-deficient human sera are chemotactically activated by incubation with immune precipitates, substantially more chemotactic activity is generated in α1-AT-deficient serum. These data indicate that in α1-AT-deficient serum there is an imbalance in the generation and control of chemotactic factors. It is suggested that the theory regarding development of pulmonary emphysema in patients lacking the α1-antitrypsin in their serum should be modified to take into account a deficiency of the chemotactic factor inactivator. PMID:4683887

  12. Vitamin B12: a novel indicator of bone health in vulnerable groups

    NARCIS (Netherlands)

    Dhonukshe-Rutten, R.A.M.

    2004-01-01

    Background: A number of modifiable predictors for osteoporosis and fractures have been identified, including nutritional factors, such as vitamin D deficiency and low calcium intake. Cobalamin deficiency has been suggested to affect bone metabolism. Pernicious anaemia, which can result in cobalamin

  13. The triad of Iron deficiency anemia, hepatosplenomegaly and ...

    African Journals Online (AJOL)

    2014-12-04

    Dec 4, 2014 ... In conclusion, iron deficiency anemia occurring in the triad without zinc deficiency as .... a negative zinc balance and mask existing zinc deficiency.[10] ... erythropoiesis‑stimulating agents in men with chronic kidney disease.

  14. Genetics Home Reference: ataxia with vitamin E deficiency

    Science.gov (United States)

    ... Conditions Ataxia with vitamin E deficiency Ataxia with vitamin E deficiency Printable PDF Open All Close All Enable ... view the expand/collapse boxes. Description Ataxia with vitamin E deficiency is a disorder that impairs the body's ...

  15. Genetics Home Reference: X-linked creatine deficiency

    Science.gov (United States)

    ... Health Conditions X-linked creatine deficiency X-linked creatine deficiency Printable PDF Open All Close All Enable ... view the expand/collapse boxes. Description X-linked creatine deficiency is an inherited disorder that primarily affects ...

  16. Genetics Home Reference: carnitine-acylcarnitine translocase deficiency

    Science.gov (United States)

    ... Email Facebook Twitter Home Health Conditions CACT deficiency Carnitine-acylcarnitine translocase deficiency Printable PDF Open All Close ... Javascript to view the expand/collapse boxes. Description Carnitine-acylcarnitine translocase (CACT) deficiency is a condition that ...

  17. Genetic, molecular and functional analyses of complement factor I deficiency

    DEFF Research Database (Denmark)

    Nilsson, S.C.; Trouw, L.A.; Renault, N.

    2009-01-01

    Complete deficiency of complement inhibitor factor I (FI) results in secondary complement deficiency due to uncontrolled spontaneous alternative pathway activation leading to susceptibility to infections. Current genetic examination of two patients with near complete FI deficiency and three patie...

  18. Genetics Home Reference: iron-refractory iron deficiency anemia

    Science.gov (United States)

    ... refractory iron deficiency anemia Iron-refractory iron deficiency anemia Printable PDF Open All Close All Enable Javascript ... expand/collapse boxes. Description Iron-refractory iron deficiency anemia is one of many types of anemia , which ...

  19. Iron Deficiency Anaemia In Reproductive Age Women Attending ...

    African Journals Online (AJOL)

    Iron Deficiency Anaemia In Reproductive Age Women Attending Obstetrics And ... prevalence of iron deficiency anemia in reproductive age women, and their relation to ... Thus iron deficiency anemia during pregnancy in well-educated set up ...

  20. Seventeen Alpha-hydroxylase Deficiency

    Directory of Open Access Journals (Sweden)

    Siew-Lee Wong

    2006-01-01

    Full Text Available Seventeen a-hydroxylase deficiency (17OHD is a rare form of congenital adrenal hyperplasia in which defects in the biosynthesis of cortisol and sex steroid result in mineralocorticoid excess, hypokalemic hypertension and sexual abnormalities such as pseudohermaphroditism in males, and sexual infantilism in females. The disease is inherited in an autosomal recessive pattern, and is caused by mutations in the gene encoding cytochrome P450c17 (CYP17, which is the single polypeptide that mediates both 17α-hydroxylase and 17,20-lyase activities. We report the case of a 15-year-old patient with 17OHD who had a female phenotype but male karyotype (46,XY. The diagnosis was made based on classical clinical features, biochemical data and molecular genetic study. Two mutations were identified by polymerase chain reaction amplification and sequencing, including a S106P point mutation in exon 2 and a 9-bp (GACTCTTTC deletion from nucleotide position 1519 in exon 8 of CYP17. The first of these mutations was found in the father and the second in the mother, and both have been previously reported in Asia. The patient's hypertension and hypokalemia resolved after glucocorticoid replacement and treatment with potassium-sparing diuretics. Sex hormone replacement was prescribed for induction of sexual development and reduction of the final height. Prophylactic gonadectomy was scheduled. In summary, 17OHD should be suspected in patients with hypokalemic hypertension and lack of secondary sexual development so that appropriate therapy can be implemented.

  1. Zinc: physiology, deficiency, and parenteral nutrition.

    Science.gov (United States)

    Livingstone, Callum

    2015-06-01

    The essential trace element zinc (Zn) has a large number of physiologic roles, in particular being required for growth and functioning of the immune system. Adaptive mechanisms enable the body to maintain normal total body Zn status over a wide range of intakes, but deficiency can occur because of reduced absorption or increased gastrointestinal losses. Deficiency impairs physiologic processes, leading to clinical consequences that include failure to thrive, skin rash, and impaired wound healing. Mild deficiency that is not clinically overt may still cause nonspecific consequences, such as susceptibility to infection and poor growth. The plasma Zn concentration has poor sensitivity and specificity as a test of deficiency. Consequently, diagnosis of deficiency requires a combination of clinical assessment and biochemical tests. Patients receiving parenteral nutrition (PN) are susceptible to Zn deficiency and its consequences. Nutrition support teams should have a strategy for assessing Zn status and optimizing this by appropriate supplementation. Nutrition guidelines recommend generous Zn provision from the start of PN. This review covers the physiology of Zn, the consequences of its deficiency, and the assessment of its status, before discussing its role in PN. © 2015 American Society for Parenteral and Enteral Nutrition.

  2. Reticulocyte maturity indices in iron deficiency anemia

    Directory of Open Access Journals (Sweden)

    Muriel Wollmann

    2014-01-01

    Full Text Available Objective: The aim of this study was to analyze the reticulocyte maturity indices (low, medium, and high fluorescence ratios in iron deficient 1- to 6-year-old children, and identify the prevalence of iron deficiency anemia in this population. Methods: The present study included 39 subjects, divided into two groups: control subjects (n = 33, and subjects with iron deficiency anemia (n = 6. The results were analyzed by Student's t-test for comparison of means. Differences were considered significant when two-tailed p-value < 0.05. Results: Subjects with iron deficiency anemia presented increases in the proportion of mean (10.3 ± 4.7% vs. 6.0 ± 3.4%; p-value = 0.003, and high fluorescence reticulocytes (2.3 ± 0.87% vs. 0.9 ± 0.9%; p-value = 0.03 compared to the control group. The prevalence of anemia in this population was 15% (n = 6. Conclusion: The indices related to immaturity of reticulocytes are higher in the presence of iron deficiency, thus demonstrating a deficiency in the raw material to form hemoglobin and are, therefore, possible early markers of iron deficiency and anemia. We emphasize the need to standardize these indices for use in clinical practice and lab test results.

  3. Syndromes associated with nutritional deficiency and excess.

    Science.gov (United States)

    Jen, Melinda; Yan, Albert C

    2010-01-01

    Normal functioning of the human body requires a balance between nutritional intake and metabolism, and imbalances manifest as nutritional deficiencies or excess. Nutritional deficiency states are associated with social factors (war, poverty, famine, and food fads), medical illnesses with malabsorption (such as Crohn disease, cystic fibrosis, and after bariatric surgery), psychiatric illnesses (eating disorders, autism, alcoholism), and medications. Nutritional excess states result from inadvertent or intentional excessive intake. Cutaneous manifestations of nutritional imbalance can herald other systemic manifestations. This contribution discusses nutritional deficiency and excess syndromes with cutaneous manifestations of particular interest to clinical dermatologists. Copyright © 2010. Published by Elsevier Inc.

  4. 2-Methylbutyryl-coenzyme A dehydrogenase deficiency

    DEFF Research Database (Denmark)

    Sass, Jörn Oliver; Ensenauer, Regina; Röschinger, Wulf

    2008-01-01

    2-Methylbutyryl-CoA dehydrogenase (MBD; coded by the ACADSB gene) catalyzes the step in isoleucine metabolism that corresponds to the isovaleryl-CoA dehydrogenase reaction in the degradation of leucine. Deficiencies of both enzymes may be detected by expanded neonatal screening with tandem...... individuals showed clinical symptoms attributable to MBD deficiency although the defect in isoleucine catabolism was demonstrated both in vivo and in vitro. Several mutations in the ACADSB gene were identified, including a novel one. MBD deficiency may be a harmless metabolic variant although significant...

  5. Hypopituitarism: growth hormone and corticotropin deficiency.

    Science.gov (United States)

    Capatina, Cristina; Wass, John A H

    2015-03-01

    This article presents an overview of adult growth hormone deficiency (AGHD) and corticotropin deficiency (central adrenal failure, CAI). Both conditions can result from various ailments affecting the hypothalamus or pituitary gland (most frequently a tumor in the area or its treatment). Clinical manifestations are subtle in AGHD but potentially life-threatening in CAI. The diagnosis needs dynamic testing in most cases. Treatment of AGHD is recommended in patients with documented severe deficiency, and treatment of CAI is mandatory in all cases. Despite significant progress in replacement hormonal therapy, more physiologic treatments and more reliable indicators of treatment adequacy are still needed. Copyright © 2015 Elsevier Inc. All rights reserved.

  6. Prevalence of Vitamin B12 and Folate Deficiencies and ...

    African Journals Online (AJOL)

    ... 2Faculty of Dentistry, International Branch, 3Department of Internal Medicine & Endocrine and ... Keywords: Vitamin B12 deficiency, Folate deficiency, Homocysteinemia, Elderly population ... gastritis, intestinal malabsorption, pancreatic.

  7. Impulsivity: A deficiency of inhibitory control?

    NARCIS (Netherlands)

    Lansbergen, M.M.

    2007-01-01

    Impulsivity has been defined as acting without thinking. Impulsivity can be quantified by impulsivity questionnaires, but also by behavioral paradigms which tax inhibitory control. Previous research has repeatedly demonstrated deficient inhibitory control in psychopathological samples characterized

  8. Genetics Home Reference: factor XIII deficiency

    Science.gov (United States)

    ... XIII deficiency tend to have heavy or prolonged menstrual bleeding (menorrhagia) and may experience recurrent pregnancy losses ( ... inheritance, which means that it results when both copies of either the F13A1 gene or the F13B ...

  9. Vitamin K deficiency bleeding of the newborn

    Science.gov (United States)

    Vitamin K deficiency bleeding of the newborn (VKDB) is a bleeding disorder in babies. It most often ... A lack of vitamin K may cause severe bleeding in newborn babies. Vitamin K plays an important role in blood clotting. Babies often ...

  10. Somatomedin C deficiency in Asian sisters.

    OpenAIRE

    McGraw, M E; Price, D A; Hill, D J

    1986-01-01

    Two sisters of Asian origin showed typical clinical and biochemical features of primary somatomedin C (SM-C) deficiency (Laron dwarfism). Abnormalities of SM-C binding proteins were observed, one sister lacking the high molecular weight (150 Kd) protein.

  11. Genetics Home Reference: cerebral folate transport deficiency

    Science.gov (United States)

    ... R. Cerebral folate deficiency syndromes in childhood: clinical, analytical, and etiologic aspects. Arch Neurol. 2011 May;68( ... 2009.08.005. Citation on PubMed or Free article on PubMed Central Toelle SP, Wille D, Schmitt ...

  12. CALCIUM DEFICIENCY AND CAUSATION OF RICKETS IN ...

    African Journals Online (AJOL)

    hi-tech

    2005-03-03

    Mar 3, 2005 ... communication about the benefits of exposing children to sunlight is very important in preventing the ... of rickets was nutritional deficiency of vitamin D due either to ..... resulting from less time being spent outdoors is the cause.

  13. Defense Logistics Agency Product Quality Deficiency Program

    National Research Council Canada - National Science Library

    1998-01-01

    .... He was interested in improving the product quality deficiency report system, which is used by DoD Components to identify and purge nonconforming material from inventory and to provide information...

  14. LACTASE DEFICIENCY IN BABIES AND INFANTS

    Directory of Open Access Journals (Sweden)

    E.A. Kornienko

    2006-01-01

    Full Text Available Lactose, the constituent disaccharide of milk and other dairy products, is an important nutrient in early childhood. Lactase breaks down lactose in small intestine. In most people the activity of lactase reduces with age. In infancy lactase deficiency tends to be either transient, which is more often, or secondary to intestinal diseases. Abdominal cramps, anxiety and dyspepsia are the common symptoms of lactase deficiency. Tactics of treatment should take into account a cause and severity of the condition. A specialized milk formula «enfamil lactofree», distinguished for its' optimal formulation, high clinical effectiveness and good tolerance, could be recommended for use in children with primary, transient and secondary lactase deficiency who receive formula and mixed feeding.Key words: lactose, lactase deficiency, lactose-free formula.

  15. Prenatal diagnosis in adenylosuccinate lyase deficiency

    NARCIS (Netherlands)

    Marie, S.; Flipsen, J. W.; Duran, M.; Poll-The, B. T.; Beemer, F. A.; Bosschaart, A. N.; Vincent, M. F.; van den Berghe, G.

    2000-01-01

    Adenylosuccinate lyase deficiency, an autosomal recessive inborn error of purine synthesis, provokes accumulation in body fluids of succinylaminoimidazolecarboxamide riboside and succinyladenosine, the dephosphorylated derivatives of the two substrates of the enzyme. Most patients display severe

  16. Genetics Home Reference: GABA-transaminase deficiency

    Science.gov (United States)

    ... Description GABA-transaminase deficiency is a brain disease (encephalopathy) that begins in infancy. Babies with this disorder ... genetic testing? What is precision medicine? What is newborn screening? New Pages LMNA-related congenital muscular dystrophy ...

  17. Neurological findings in triosephosphate isomerase deficiency

    NARCIS (Netherlands)

    Poll-The, B. T.; Aicardi, J.; Girot, R.; Rosa, R.

    1985-01-01

    Two siblings with hemolytic anemia caused by triosephosphate isomerase deficiency developed a progressive neurological syndrome featuring dystonic movements, tremor, pyramidal tract signs, and evidence of spinal motor neuron involvement. Intelligence was unaffected. The findings in these patients

  18. VITAMIN A DEFICIENCY IN NIGERIAN CHILDREN

    African Journals Online (AJOL)

    Dr Olaleye

    Vitamin A deficiency (VAD) is a global problem of public health significance in many ... It is therefore important to know Vitamin A status of. Nigerian ..... Ph D thesis University of Ibadan. Ajaiyeoba AI (1994). Childhood blindness in Nigeria.

  19. Genetics Home Reference: familial glucocorticoid deficiency

    Science.gov (United States)

    ... deficiency Patient Support and Advocacy Resources (5 links) Australian Pituitary Foundation: An Introduction to Adrenal Insufficiency in ... API Site Map Subscribe Customer Support USA.gov Copyright Privacy Accessibility FOIA Viewers & Players U.S. Department of ...

  20. Isoprenoid biosynthesis and mevalonate kinase deficiency

    NARCIS (Netherlands)

    Henneman, L.

    2011-01-01

    Mevalonaat Kinase Deficiëntie (MKD) is een aangeboren ziekte geassocieerd met heftige koortsaanvallen die drie tot vier dagen aanhouden en gepaard gaan met koude rillingen, gewrichtsklachten, huiduitslag, hoofdpijn, duizeligheid, buikpijn, braken en diarree. De koortsaanvallen treden gemiddeld eens

  1. FastStats: Anemia or Iron Deficiency

    Science.gov (United States)

    ... this? Submit What's this? Submit Button NCHS Home Anemia or Iron Deficiency Recommend on Facebook Tweet Share ... visits Number of visits to emergency departments with anemia as the primary hospital discharge diagnosis: 188,000 ...

  2. Genetics Home Reference: isolated sulfite oxidase deficiency

    Science.gov (United States)

    ... and Management Resources (1 link) GeneReview: Isolated Sulfite Oxidase Deficiency General Information from MedlinePlus (5 links) Diagnostic Tests Drug Therapy Genetic Counseling Palliative Care Surgery and ...

  3. Experimental reproduction of iodine deficiency in cattle.

    Science.gov (United States)

    McCoy, M A; Smyth, J A; Ellis, W A; Arthur, J R; Kennedy, D G

    1997-11-22

    The role of iodine deficiency in stillbirth/perinatal weak calf syndrome was investigated in pregnant heifers. Five heifers were fed an iodine deficient diet (mean [sd] iodine concentration 0.06 [0.01] mg/kg dry matter [DM]) and six received an iodine sufficient diet (mean [sd] iodine concentration 1.45 [0.27] mg/kg DM). The diets consisted of wheat and soyabean meal with added minerals and vitamins (with or without iodine) and were fed to the heifers over the final four to five months of pregnancy. The iodine deficient diet produced clinicopathological changes and pathological changes in the thyroid glands of both the heifers and their offspring. However, all the calves in the iodine deficient group were born clinically normal.

  4. Office ergonomics: deficiencies in computer workstation design.

    Science.gov (United States)

    Shikdar, Ashraf A; Al-Kindi, Mahmoud A

    2007-01-01

    The objective of this research was to study and identify ergonomic deficiencies in computer workstation design in typical offices. Physical measurements and a questionnaire were used to study 40 workstations. Major ergonomic deficiencies were found in physical design and layout of the workstations, employee postures, work practices, and training. The consequences in terms of user health and other problems were significant. Forty-five percent of the employees used nonadjustable chairs, 48% of computers faced windows, 90% of the employees used computers more than 4 hrs/day, 45% of the employees adopted bent and unsupported back postures, and 20% used office tables for computers. Major problems reported were eyestrain (58%), shoulder pain (45%), back pain (43%), arm pain (35%), wrist pain (30%), and neck pain (30%). These results indicated serious ergonomic deficiencies in office computer workstation design, layout, and usage. Strategies to reduce or eliminate ergonomic deficiencies in computer workstation design were suggested.

  5. Thyroid disorders in mild iodine deficiency

    DEFF Research Database (Denmark)

    Laurberg, P; Nøhr, S B; Pedersen, K M

    2000-01-01

    Comparative epidemiologic studies in areas with low and high iodine intake and controlled studies of iodine supplementation have demonstrated that the major consequence of mild-to-moderate iodine deficiency for the health of the population is an extraordinarily high occurrence of hyperthyroidism...... endangered but the consequences of severe iodine deficiency for brain development are grave and a considerable safety margin is advisable. Moreover, a shift toward less malignant types of thyroid cancer and a lower radiation dose to the thyroid in case of nuclear fallout support that mild-to-moderate iodine...... deficiency should be corrected. However, there is evidence that a high iodine intake may be associated with more autoimmune hypothyroidism, and that Graves' disease may manifest at a younger age and be more difficult to treat. Hence, the iodine intake should be brought to a level at which iodine deficiency...

  6. Study of neutron-deficient Sn isotopes

    International Nuclear Information System (INIS)

    Auger, G.

    1982-05-01

    The formation of neutron deficient nuclei by heavy ion reactions is investigated. The experimental technique is presented, and the results obtained concerning Sn et In isotopes reported: first excited states of 106 Sn, high spin states in 107 Sn and 107 In; Yrast levels of 106 Sn, 107 Sn, 108 Sn; study of neutron deficient Sn and In isotopes formed by the desintegration of the compound nucleus 112 Xe. All these results are discussed [fr

  7. Iron deficiency and anemia in heart failure.

    Science.gov (United States)

    Çavuşoğlu, Yüksel; Altay, Hakan; Çetiner, Mustafa; Güvenç, Tolga Sinan; Temizhan, Ahmet; Ural, Dilek; Yeşilbursa, Dilek; Yıldırım, Nesligül; Yılmaz, Mehmet Birhan

    2017-03-01

    Heart failure is an important community health problem. Prevalence and incidence of heart failure have continued to rise over the years. Despite recent advances in heart failure therapy, prognosis is still poor, rehospitalization rate is very high, and quality of life is worse. Co-morbidities in heart failure have negative impact on clinical course of the disease, further impair prognosis, and add difficulties to treatment of clinical picture. Therefore, successful management of co-morbidities is strongly recommended in addition to conventional therapy for heart failure. One of the most common co-morbidities in heart failure is presence of iron deficiency and anemia. Current evidence suggests that iron deficiency and anemia are more prevalent in patients with heart failure and reduced ejection fraction, as well as those with heart failure and preserved ejection fraction. Moreover, iron deficiency and anemia are referred to as independent predictors for poor prognosis in heart failure. There is strong relationship between iron deficiency or anemia and severity of clinical status of heart failure. Over the last two decades, many clinical investigations have been conducted on clinical effectiveness of treatment of iron deficiency or anemia with oral iron, intravenous iron, and erythropoietin therapies. Studies with oral iron and erythropoietin therapies did not provide any clinical benefit and, in fact, these therapies have been shown to be associated with increase in adverse clinical outcomes. However, clinical trials in patients with iron deficiency in the presence or absence of anemia have demonstrated considerable clinical benefits of intravenous iron therapy, and based on these positive outcomes, iron deficiency has become target of therapy in management of heart failure. The present report assesses current approaches to iron deficiency and anemia in heart failure in light of recent evidence.

  8. Dietary phytate, zinc and hidden zinc deficiency.

    Science.gov (United States)

    Sandstead, Harold H; Freeland-Graves, Jeanne H

    2014-10-01

    Epidemiological data suggest at least one in five humans are at risk of zinc deficiency. This is in large part because the phytate in cereals and legumes has not been removed during food preparation. Phytate, a potent indigestible ligand for zinc prevents it's absorption. Without knowledge of the frequency of consumption of foods rich in phytate, and foods rich in bioavailable zinc, the recognition of zinc deficiency early in the illness may be difficult. Plasma zinc is insensitive to early zinc deficiency. Serum ferritin concentration≤20μg/L is a potential indirect biomarker. Early effects of zinc deficiency are chemical, functional and may be "hidden". The clinical problem is illustrated by 2 studies that involved US Mexican-American children, and US premenopausal women. The children were consuming home diets that included traditional foods high in phytate. The premenopausal women were not eating red meat on a regular basis, and their consumption of phytate was mainly from bran breakfast cereals. In both studies the presence of zinc deficiency was proven by functional responses to controlled zinc treatment. In the children lean-mass, reasoning, and immunity were significantly affected. In the women memory, reasoning, and eye-hand coordination were significantly affected. A screening self-administered food frequency questionnaire for office might help caregiver's identify patients at risk of zinc deficiency. Copyright © 2014 Elsevier GmbH. All rights reserved.

  9. Glucose 6 phosphate dehydrogenase deficiency in adults

    International Nuclear Information System (INIS)

    Khan, M.

    2004-01-01

    Objective: To determine the frequency of glucose-6-phosphate dehydrogenase (G6PD) deficiency in adults presented with anemia. Subjects and Methods: Eighteen months admission data was reviewed for G6PD deficiency as a cause of anemia. Anemia was defined by world health organization (WHO) criteria as haemoglobin less than 11.3 gm%. G6PD activity was measured by Sigma dye decolorisation method. All patients were screened for complications of hemolysis and its possible cause. Patients with more than 13 years of age were included in the study. Results: Out of 3600 patients admitted, 1440 were found anaemic and 49 as G6PD deficient. So the frequency of G6PD deficiency in anaemic patients was 3.4% and the overall frequency is 1.36%. G6PD deficiency among males and females was three and six percent respectively. Antimalarials and antibiotics containing sulphonamide group were the most common precipitating factors for hemolysis. Anemia and jaundice were the most common presentations while malaria was the most common associated disease. Acute renal failure was the most severe complication occurring in five patients with two deaths. Conclusion: G6PD deficiency is a fairly common cause of anemia with medicine as common precipitating factor for hemolysis. Such complications can be avoided with early recognition of the disease and avoiding indiscriminate use of medicine. (author)

  10. PPARgamma Deficiency Counteracts Thymic Senescence

    Directory of Open Access Journals (Sweden)

    David Ernszt

    2017-11-01

    Full Text Available Thymic senescence contributes to increased incidence of infection, cancer and autoimmunity at senior ages. This process manifests as adipose involution. As with other adipose tissues, thymic adipose involution is also controlled by PPARgamma. This is supported by observations reporting that systemic PPARgamma activation accelerates thymic adipose involution. Therefore, we hypothesized that decreased PPARgamma activity could prevent thymic adipose involution, although it may trigger metabolic adverse effects. We have confirmed that both human and murine thymic sections show marked staining for PPARgamma at senior ages. We have also tested the thymic lobes of PPARgamma haplo-insufficient and null mice. Supporting our working hypothesis both adult PPARgamma haplo-insufficient and null mice show delayed thymic senescence by thymus histology, thymocyte mouse T-cell recombination excision circle qPCR and peripheral blood naive T-cell ratio by flow-cytometry. Delayed senescence showed dose–response with respect to PPARgamma deficiency. Functional immune parameters were also evaluated at senior ages in PPARgamma haplo-insufficient mice (null mice do not reach senior ages due to metabolic adverse affects. As expected, sustained and elevated T-cell production conferred oral tolerance and enhanced vaccination efficiency in senior PPARgamma haplo-insufficient, but not in senior wild-type littermates according to ELISA IgG measurements. Of note, humans also show increased oral intolerance issues and decreased protection by vaccines at senior ages. Moreover, PPARgamma haplo-insufficiency also exists in human known as a rare disease (FPLD3 causing metabolic adverse effects, similar to the mouse. When compared to age- and metabolic disorder-matched other patient samples (FPLD2 not affecting PPARgamma activity, FPLD3 patients showed increased human Trec (hTrec values by qPCR (within healthy human range suggesting delayed thymic senescence, in accordance with

  11. Associação da deficiência de ácido fólico com alterações patológicas e estratégias para sua prevenção: uma visão crítica Association between folic acid deficiency and disease and prevention strategies: a critical view

    Directory of Open Access Journals (Sweden)

    Sofia Kimi Uehara

    2010-10-01

    Full Text Available A deficiência de ácido fólico está associada às doenças crônicas não-transmissíveis, complicações na gestação e doenças neurodegenerativas. Objetivou-se discutir o papel do ácido fólico na prevenção de doenças, os aspectos epidemiológicos de sua deficiência, fortificação dos alimentos e suplementação medicamentosa. Realizou-se levantamento bibliográfico, consultando as bases de dados para a obtenção dos artigos completos: MedLine, SciELO, PubMed, Highwire Press e Science Direct. Foram selecionados estudos realizados com seres humanos publicados entre 2004 e 2010. O ácido fólico é importante para as reações de metilação do ácido desoxirribonucléico, prevenção da hiper-homocisteinemia e atua como antioxidante. A deficiência dessa vitamina é descrita em adolescentes, mulheres em idade fértil, gestantes e em idosos. Seu alcance pela dieta é difícil, sendo necessária a inclusão de alimentos fortificados ou suplementos. É importante avaliar o estado nutricional de ácido fólico dos indivíduos antes e após a adoção dessas estratégias, de modo a gerar subsídios para ela-boração de medidas governamentais mais adequadas e eficazes. Destacamos ainda a necessidade da reeducação nutricional para a população brasileira a fim de aumentar o consumo de alimentos fontes de ácido fólico.Folic acid deficiency is associated with non-communicable chronic diseases, pregnancy-associated complications and neurodegenerative diseases. The objective of this paper was to discuss the role of folic acid in disease prevention, the epidemiological aspects of its deficiency and food fortification and supplementation. Articles were searched in the following databases: MedLine, SciELO, PubMed, Highwire Press and Science Direct. Only original studies with humans published between 2004 and 2010 were included. Folic acid is important for DNA methylation and prevention of hyperhomocysteinemia. It also presents antioxidant

  12. Iron deficiency anaemia among apparently healthy pre-school ...

    African Journals Online (AJOL)

    Background: Iron deficiency, and specifically iron deficiency anaemia, remains one of the most severe and important nutritional deficiencies in the world today. Objective: To estimate the prevalence and associated factors for iron deficiency anaemia among pre-school children in Lagos. Methodology: The study was ...

  13. In HepG2 cells, coexisting carnitine deficiency masks important indicators of marginal biotin deficiency.

    Science.gov (United States)

    Bogusiewicz, Anna; Boysen, Gunnar; Mock, Donald M

    2015-01-01

    A large number of birth defects are related to nutrient deficiencies; concern that biotin deficiency is teratogenic in humans is reasonable. Surprisingly, studies indicate that increased urinary 3-hydroxyisovalerylcarnitine (3HIAc), a previously validated marker of biotin deficiency, is not a valid biomarker in pregnancy. In this study we hypothesized that coexisting carnitine deficiency can prevent the increase in 3HIAc due to biotin deficiency. We used a 2-factor nutrient depletion design to induce isolated and combined biotin and carnitine deficiency in HepG2 cells and then repleted cells with carnitine. To elucidate the metabolic pathogenesis, we quantitated intracellular and extracellular free carnitine, acylcarnitines, and acylcarnitine ratios using liquid chromatography-tandem mass spectrometry. Relative to biotin-sufficient, carnitine-sufficient cells, intracellular acetylcarnitine increased by 90%, propionylcarnitine more than doubled, and 3HIAc increased by >10-fold in biotin-deficient, carnitine-sufficient (BDCS) cells, consistent with a defensive mechanism in which biotin-deficient cells transesterify the acyl-coenzyme A (acyl-CoA) substrates of the biotin-dependent carboxylases to the related acylcarnitines. Likewise, in BDCS cells, the ratio of acetylcarnitine to malonylcarnitine and the ratio of propionylcarnitine to methylmalonylcarnitine both more than tripled, and the ratio of 3HIAc to 3-methylglutarylcarnitine (MGc) increased by >10-fold. In biotin-deficient, carnitine-deficient (BDCD) cells, the 3 substrate-derived acylcarnitines changed little, but the substrate:product ratios were masked to a lesser extent. Moreover, carnitine repletion unmasked biotin deficiency in BDCD cells as shown by increases in acetylcarnitine, propionylcarnitine, and 3HIAc (each increased by >50-fold). Likewise, ratios of acetylcarnitine:malonylcarnitine, propionylcarnitine:methylmalonylcarnitine, and 3HIAc:MGc all increased by >8-fold. Our findings provide strong

  14. Sleep transitions in hypocretin-deficient narcolepsy.

    Science.gov (United States)

    Sorensen, Gertrud Laura; Knudsen, Stine; Jennum, Poul

    2013-08-01

    Narcolepsy is characterized by instability of sleep-wake, tonus, and rapid eye movement (REM) sleep regulation. It is associated with severe hypothalamic hypocretin deficiency, especially in patients with cataplexy (loss of tonus). As the hypocretin neurons coordinate and stabilize the brain's sleep-wake pattern, tonus, and REM flip-flop neuronal centers in animal models, we set out to determine whether hypocretin deficiency and/or cataplexy predicts the unstable sleep-wake and REM sleep pattern of the human phenotype. We measured the frequency of transitions in patients with narcolepsy between sleep-wake states and to/from REM and NREM sleep stages. Patients were subdivided by the presence of +/- cataplexy and +/- hypocretin-1 deficiency. Sleep laboratory studies conducted from 2001-2011. In total 63 narcolepsy patients were included in the study. Cataplexy was present in 43 of 63 patients and hypocretin-1 deficiency was present in 37 of 57 patients. Hypocretin-deficient patients with narcolepsy had a significantly higher frequency of sleep-wake transitions (P = 0.014) and of transitions to/from REM sleep (P = 0.044) than patients with normal levels of hypocretin-1. Patients with cataplexy had a significantly higher frequency of sleep-wake transitions (P = 0.002) than those without cataplexy. A multivariate analysis showed that transitions to/from REM sleep were predicted mainly by hypocretin-1 deficiency (P = 0.011), whereas sleep-wake transitions were predicted mainly by cataplexy (P = 0.001). In human narcolepsy, hypocretin deficiency and cataplexy are both associated with signs of destabilized sleep-wake and REM sleep control, indicating that the disorder may serve as a human model for the sleep-wake and REM sleep flip-flop switches.

  15. Iron deficiency anemia from diagnosis to treatment in children

    OpenAIRE

    Özdemir, Nihal

    2015-01-01

    Iron deficiency is the most common nutritional deficiency worldwide and an important public health problem especially in developing countries. Since the most important indicator of iron deficieny is anemia, the terms “iron deficiency” and “iron deficiency anemia” are often used interchangeably. However, iron deficiency may develop in the absence of anemia and the tissues may be affected from this condition. The most common causes of iron deficiency in children include insufficient intake toge...

  16. Zinc Deficiency in Humans and its Amelioration

    Directory of Open Access Journals (Sweden)

    Yashbir Singh Shivay

    2015-01-01

    Full Text Available Zinc (Zn deficiency in humans has recently received considerable attention. Global mortality in children under 5 years of age in 2004 due to Zn deficiency was estimated at 4,53,207 as against 6,66,771 for vitamin A deficiency; 20,854 for iron deficiency and 3,619 for iodine deficiency. In humans 2800-3000 proteins contain Zn prosthetic group and Zn is an integral component of zinc finger prints that regulate DNA transcription. Zinc is a Type-2 nutrient, which means that its concentration in blood does not decrease in proportion of the Zn deficiency. Adverse effects of Zn deficiency vary with age: low weight gain, diarrhoea, aneroxia and neurobehavioral disturbances are observed in infants, while skin changes and dwarfism are frequent in toddlers and adolescents. Common manifestations of Zn deficiency among elderly include hypogeusia, chronic non-healing ulcers and recurrent infections.Ameliorative measures of Zn deficiency in humans can be classified in two groups, namely, nutraceutical and biofortification of food grains. Nutraceutical interventions include pharmaceutical supplements, dietary supplements and dietary diversification, while biofortification of food grains can be achieved by genetic modification (GM of crops or by agronomic techniques that include soil or/and foliar fertilization of crops.The major disadvantage of nutraceutical approaches is that the major beneficiaries are urban people and the poor rural masses that need adequate Zn nutrition most are left out. Genetic biofortification of food grains requires large amounts of funds and a fairly long-period of time. Further, a large number of countries have not yet accepted genetically modified (GM foods. On the other hand agronomic biofortification of food grains yields immediate effects and rural and urban people are equally benefitted. Our studies have shown that Zn concentration in cereals (rice, wheat etc and pulses can be considerably increased by soil or/and foliar

  17. Vitamin D Deficiency Among Professional Basketball Players.

    Science.gov (United States)

    Fishman, Matthew P; Lombardo, Stephen J; Kharrazi, F Daniel

    2016-07-01

    Vitamin D plays an important role in several systems of the human body. Various studies have linked vitamin D deficiency to stress and insufficiency fractures, muscle recovery and function, and athletic performance. The prevalence of vitamin D deficiency in the elite athletic population has not been extensively studied, and very few reports exist among professional athletes. There is a high prevalence of vitamin D deficiency or insufficiency among players attending the National Basketball Association (NBA) Combine. Cross-sectional study; Level of evidence, 3. This is a retrospective review of data previously collected as part of the routine medical evaluation of players in the NBA Combines from 2009 through 2013. Player parameters evaluated were height, weight, body mass index (BMI), and vitamin D level. Statistical analysis using t tests and analysis of variance was used to detect any correlation between the player parameters and vitamin D level. Vitamin D levels were categorized as deficient (32 ng/mL). After institutional review board approval was submitted to the NBA, the NBA released deidentified data on 279 players who participated in the combines from 2009 through 2013. There were 90 players (32.3%) who were deficient, 131 players (47.0%) who were insufficient, and 58 players (20.8%) who were sufficient. A total of 221 players (79.3%) were either vitamin D deficient or insufficient. Among all players included, the average vitamin D level was 25.6 ± 10.2 ng/mL. Among the players who were deficient, insufficient, and sufficient, the average vitamin D levels were 16.1 ± 2.1 ng/mL, 25.0 ± 3.4 ng/mL, and 41.6 ± 8.6 ng/mL, respectively. Player height and weight were significantly increased in vitamin D-sufficient players compared with players who were not sufficient (P = .0008 and .009, respectively). Player age and BMI did not significantly differ depending on vitamin D status (P = .15 and .77, respectively). There is a high prevalence of vitamin D deficiency

  18. Zinc Deficiency in Humans and its Amelioration

    Directory of Open Access Journals (Sweden)

    Yashbir Singh Shivay

    2015-12-01

    Full Text Available Zinc (Zn deficiency in humans has recently received considerable attention. Global mortality in children under 5 years of age in 2004 due to Zn deficiency was estimated at 4,53,207 as against 6,66,771 for vitamin A deficiency; 20,854 for iron deficiency and 3,619 for iodine deficiency. In humans 2800-3000 proteins contain Zn prosthetic group and Zn is an integral component of zinc finger prints that regulate DNA transcription. Zinc is a Type-2 nutrient, which means that its concentration in blood does not decrease in proportion of the Zn deficiency. Adverse effects of Zn deficiency vary with age: low weight gain, diarrhoea, aneroxia and neurobehavioral disturbances are observed in infants, while skin changes and dwarfism are frequent in toddlers and adolescents. Common manifestations of Zn deficiency among elderly include hypogeusia, chronic non-healing ulcers and recurrent infections. Ameliorative measures of Zn deficiency in humans can be classified in two groups, namely, nutraceutical and biofortification of food grains. Nutraceutical interventions include pharmaceutical supplements, dietary supplements and dietary diversification, while biofortification of food grains can be achieved by genetic modification (GM of crops or by agronomic techniques that include soil or/and foliar fertilization of crops. The major disadvantage of nutraceutical approaches is that the major beneficiaries are urban people and the poor rural masses that need adequate Zn nutrition most are left out. Genetic biofortification of food grains requires large amounts of funds and a fairly long-period of time. Further, a large number of countries have not yet accepted genetically modified (GM foods. On the other hand agronomic biofortification of food grains yields immediate effects and rural and urban people are equally benefitted. Our studies have shown that Zn concentration in cereals (rice, wheat etc and pulses can be considerably increased by soil or/and foliar

  19. Clinical implications of vitamin D deficiency

    Directory of Open Access Journals (Sweden)

    Beata Matyjaszek-Matuszek

    2015-06-01

    Full Text Available Vitamin D deficiency is a common medical problem worldwide and its prevalence rises along with latitude, obesity, sedentary lifestyle, limited sunlight exposure and aging. A great body of evidence has shown that patients with vitamin D deficiency have increased cardiovascular risks and total mortality. Conversely, the presence of comorbidities progressive with age such as abdominal obesity, insulin resistance, type 2 diabetes and hypertension places the patients at an increased risk of vitamin D deficiency. The multidirectional effect of vitamin D deficiency is present in different phases of the aging process. Based on the literature review, the risk factors for vitamin D insufficiency most often found in post-menopausal women include limited sun exposure and time spent outdoors, inadequate dietary vitamin D intake, winter season and increased age. Vitamin D supplementation in this group might offer prevention of falls and fractures and may be beneficial for cardiovascular health, what may be especially important in osteoporotic and elderly populations. Prevention and treatment processes involve education regarding sunlight exposure and pharmacological cholecalciferol supplementation according to the recommendations for Central Europe. This manuscript reviews the role of vitamin D and its deficiency and considers their clinical implications, with particular regard to peri- and postmenopausal women.

  20. Biochemical Assessment of Coenzyme Q10 Deficiency

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    Juan Carlos Rodríguez-Aguilera

    2017-03-01

    Full Text Available Coenzyme Q10 (CoQ10 deficiency syndrome includes clinically heterogeneous mitochondrial diseases that show a variety of severe and debilitating symptoms. A multiprotein complex encoded by nuclear genes carries out CoQ10 biosynthesis. Mutations in any of these genes are responsible for the primary CoQ10 deficiency, but there are also different conditions that induce secondary CoQ10 deficiency including mitochondrial DNA (mtDNA depletion and mutations in genes involved in the fatty acid β-oxidation pathway. The diagnosis of CoQ10 deficiencies is determined by the decrease of its content in skeletal muscle and/or dermal skin fibroblasts. Dietary CoQ10 supplementation is the only available treatment for these deficiencies that require a rapid and distinct diagnosis. Here we review methods for determining CoQ10 content by HPLC separation and identification using alternative approaches including electrochemical detection and mass spectrometry. Also, we review procedures to determine the CoQ10 biosynthesis rate using labeled precursors.